In the United States, hospitalized patients are at risk of acquiring health careassociated infections that increase morbidity, mortality, length of hospital stay, and cost of care.1 If a health careassociated infection is caused by an antimicrobial‐resistant pathogen, treatment efforts may be further complicated.2, 3 With the decreasing effectiveness of antimicrobials and suboptimal adherence to certain infection control measures, new and multifaceted prevention strategies are necessary to address the problem of health careassociated infections and antimicrobial resistance.410

One strategy that hospitals can use to reduce the incidence of health careassociated infections and antimicrobial resistance is implementation of quality improvement programs. These programs require clinicians to employ techniques, such as root cause analysis (RCA), which investigates contributing factors to an event to prevent reoccurrence, and healthcare failure mode effects analysis (HFMEA), which applies a systematic method of identifying and preventing problems before they occur.1113 Programs and strategies such as these require leadership and adoption within the hospital. Because of their availability and specialized role in the hospital setting, hospitalists are in a unique position to promote and uphold quality improvement efforts.1417 Professional societies, health care organizations, and governmental agencies can play a role in engaging this group of physicians in improving the quality of patient care in hospitals by providing educational programs and materials.18

In 2004, the Society of Hospital Medicine (SHM) collaborated with the Centers for Disease Control and Prevention (CDC) to develop a quality improvement tool kit to reduce antimicrobial resistance and health careassociated infections. The tool kit was based on the CDC's Campaign to Prevent Antimicrobial Resistance in Healthcare Settings (Campaign), an educational program targeted at clinicians.19 The SHM/CDC tool kit contained campaign materials, a set of slides about quality improvement, worksheets, and additional materials such as infection control policies and guidelines to supplement a 90‐minute workshop consisting of didactic lectures about antimicrobial resistance, quality improvement initiatives, RCA, and HFMEA; a lecture and case study about intravascular catheter‐related infections; and small‐group activity and discussion. The complete toolkit is now available online via the SHM Antimicrobial Resistance Resource Room at http://www.hospitalmedicine.org/AM/Template.cfm?Section=Home&Template=/CM/HTMLDisplay.cfm&ContentID=7542.

The purpose of the workshop was to present the tool kit and increase hospitalists' knowledge and awareness about antimicrobial resistance, health careassociated infections, and quality improvement programs. We assessed the workshop participants' familiarity with the Campaign prior to the workshop, perceptions of antimicrobial resistance, knowledge gained as a result of the workshop, and opinions about the usefulness of the workshop.

METHODS

Data were collected from pretests and posttests administered to participants of one of the SHM workshops in May, June, or July 2005 in Denver, Colorado; Boston, Massachusetts; or Portland, Oregon. One SHM physician leader (D.D.D., coauthor of this article) presented all 3 workshops. The workshops were advertised by SHM using E‐mail to local chapter members. Individual sites used a variety of methods to encourage their hospitalists to attend, and participants were provided a complimentary dinner.

Prior to each workshop, participants completed a 10‐question pretest that had been pilot‐tested by hospitalists in other cities. The pretest assessed demographics; perceptions of the problem of antimicrobial resistance using a Likert scale; familiarity with the Campaign; and knowledge of common infection sites, RCA, HFMEA, and antimicrobial resistance prevention measures.

Immediately following each workshop, a 13‐question posttest was administered to participants. This posttest evaluated the workshop and materials using Likert scales, asked for suggestions for future programming using open‐ended questions, and repeated pretest questions to assess changes in perceptions and knowledge.

Data were entered into an Excel spreadsheet and analyzed using descriptive statistics and t tests to compare pre‐ and posttest changes in knowledge. Likert data assessing perceptions were dichotomized into strongly agree versus all other scale responses. Qualitative open‐ended responses were categorized by theme.

RESULTS

A total of 69 SHM members attended the workshops. Of the 69 participants, 65 completed the pretest, 53 completed the posttest, and 50 completed both the pre‐ and the posttests. Only participants who completed both the pretest and the posttest were included in the analyses (n = 21, Denver; n = 11, Boston; n = 18, Portland). Of the 50 participants who completed both the pre‐ and posttests, 44 (88%) classified themselves as hospitalists in practices ranging from 2 to more than 25 physicians. Participants averaged 9.2 years (range = 1‐27 years) in practice and 4.9 years (range = 1‐10 years) as practicing hospitalists, with no significant differences between the 3 groups. Only 17 participants (34%) were familiar with the Campaign prior to the workshop, and there was no significant variation between the 3 workshops. Those familiar with the Campaign had heard about or received the educational materials from colleagues (n = 5), their facilities (n = 4), professional journals (n = 4), medical conferences (n = 4), or the CDC or SHM websites (n = 4).

Overall, most participants strongly agreed with the statement that antimicrobial resistance was a problem nationally, institutionally, and within their individual practices (Table 1). These perceptions did not significantly differ between the pretest and the posttest. However, statistically significant differences were found when comparing perceptions of the problem of antimicrobial resistance at the national, institutional, and practice levels; more participants strongly agreed that antimicrobial resistance was a problem nationally than within their institutions (pretest, P = .01; posttest, P = .04) or within their practices (pretest, P < .0001; posttest, P = .01).

On the knowledge‐based questions, the overall average test score was 48% on the pretest and 63% on the posttest (P < .0001), with scores varying by question (Table 2). For example, knowledge of quality improvement initiatives/HFMEA was low (an average of 10% correct on the pretest, 48% on the posttest) compared with knowledge about the key prevention strategies from the Campaign to Prevent Antimicrobial Resistance (average of 94% correct on the pretest, 98% on the posttest). Furthermore, scores also varied by workshop location. On the pretest, participants in Boston and Portland scored higher (both 53%) than Denver participants (40%). On the posttest, Portland participants scored the highest (78%) followed by Boston participants (64%) and then Denver participants (50%). Boston and Denver participants differed significantly on pretest knowledge score (P = .04) and Portland and Denver participants differed significantly on posttest knowledge score (P < .0001).

Overall, 43 participants (85%) rated the workshop as either very good or excellent. All but 1 participant (n = 49, 98%) would encourage a colleague to attend the workshop, giving reasons such as that the workshop outlined a major program in delivering good and safe care, offered great information on antimicrobial resistance and methods of quality improvement systems implementation, assisted in find[ing] new tools for improving hospital practice, and addressed a significant factor in hospitals related to morbidity [and] mortality. When asked for general comments about the workshop and suggestions for future improvements, participants requested more direction, more detail, more discussion, specific examples of antimicrobial resistance, and protocols and processes for implementing quality improvement programs. On a scale from 1 (not useful) to 5 (essential), participants rated the usefulness of each workshop segment: intravascular catheter‐related infections lecture and case study (x̄ = 4.3, range = 3‐5), quality improvement initiatives lecture (x̄ = 4.1, range = 2‐5), background on antimicrobial resistance (x̄ = 3.9, range = 2‐5), RCA lecture (x̄ = 3.9, range = 2‐5), HFMEA lecture (x̄ = 3.8, range = 2‐5), and small‐group discussion (x̄ = 3.4, range = 2‐5). These ratings did not vary significantly between the 3 groups.

CONCLUSIONS

To address antimicrobial resistance and health careassociated infections in the hospital setting, the SHM and CDC developed a tool kit and presented a quality improvement workshop to hospitalists in 3 U.S. cities. Overall, the participants scored significantly higher on the knowledge‐based questions on the posttest than on the pretest, indicating that knowledge improved as a result of the workshop. By providing a format that combined didactic lectures with case‐based education, small‐group activities, and discussion, the SHM workshop may have optimized its ability to increase knowledge, similar to the findings in previous research.2021

There were no significant differences between the 3 groups in years of practice, perceptions of the problem, and overall evaluation of the workshop. However, differences were found in knowledge gained as a result of the workshop. For example, the Denver group scored lower on the knowledge‐based questions than did the Boston group on the pretest and the Portland group on the posttest, indicating that knowledge and learning styles may differ by location. These differences may be attributed to variations in hospital environments, hospital‐based educational programs, or medical school and residency training. Differences like these may impact the effectiveness of a program and should be a consideration in the program development process, especially when a program is national in scope, like the CDC's Campaign to Prevent Antimicrobial Resistance in Healthcare Settings. In addition, more than 90% of participants correctly identified key prevention strategies of the Campaign, whereas only 34% were familiar with the Campaign itself prior to the workshop. This result may be a result of the key prevention strategies of the Campaign being derived from well‐established and ‐recognized evidence‐based best practices for patient safety and care.

Although knowledge changed as a result of the workshop, overall perceptions of the problem of antimicrobial resistance did not change significantly from pretest to posttest. It is possible this is because changes in perception require a different or more intensive educational approach. This result also may reflect the initial levels of agreement on the pretest, the measurement instrument itself, and/or the inability to detect differences because of the small number of participants.

Difference did exist in perceptions of the problem of antimicrobial resistance at the national, institutional, and practice levels. Antimicrobial resistance was perceived to be a greater problem on the national level than on the institutional and practice levels. Other studies also have found that clinicians more strongly agree that antimicrobial resistance is a problem nationally than within their institutions and practices.2224 When antimicrobial resistance is not perceived as a problem within institutions and practices, physicians may be less likely to overcome the barriers to following recommended infection prevention guidelines or to implementing quality improvement projects.4 Therefore, educational and intervention efforts like this workshop should address hospitalists' perceptions of the problem of antimicrobial resistance on the individual level as a first step in motivating them to engage in quality improvement.

Although participants' knowledge scores increased from pretest to posttest, gaps in knowledge remained, as indicated by the significantly improved but low overall posttest scores related to RCA and HFMEA. As hospitalists are in a unique position to promote quality improvement programs, these topic areas should be given more attention in future workshops and in training. Furthermore, by adding more specific questions related to each section of the workshop, associations among presentation style, knowledge gained, and perceived usefulness of each section could be evaluated. For example, the participants significantly increased their scores from pretest to posttest on the catheter‐related knowledge‐based question and rated the lecture and case study on intravascular catheter‐related infections as the most useful sections. Future research may explore these possible relationships to better guide selection of presentation styles and topics to ensure that participants gain knowledge and perceive the sections as useful. In addition, by addressing the feedback from participants, such as offering more detail, examples, and discussion, future workshops may have greater perceived usefulness and be better able to increase the knowledge and awareness of quality improvement programs for the prevention of health careassociated infections and antimicrobial resistance.

Although there were 3 workshops conducted in 3 areas across the United States, the sample size at each site was small, and results may not be representative of hospitalists at large. In addition, power calculations should be considered in future studies to increase the ability to better detect differences between and within groups. Another limitation of this study was that the limited data available and participant anonymity meant it was not possible to follow‐up with participants after the workshop to evaluate whether the knowledge they gained was sustained and/or whether they reported changes in practice. However, possession of knowledge and skills to inform practice does not mean that practice will change; therefore, follow‐up is necessary to determine if this workshop was effective in changing behaviors in the long term.25 Although the SHM workshop improved knowledge, more intensive educational strategies may be necessary to affect perceptions and improve the leadership skills required for implementation of quality improvement programs at an institutional level.

Overall, the SHM workshop was found to be a useful tool for increasing knowledge and outlining methods by which hospitalists can lead, coordinate, or participate in measures to prevent infections and improve patient safety. In addition, through the workshop, the SHM and the CDC have provided an example of how professional societies and government agencies can collaborate to address emerging issues in the health care setting.

In the United States, hospitalized patients are at risk of acquiring health careassociated infections that increase morbidity, mortality, length of hospital stay, and cost of care.1 If a health careassociated infection is caused by an antimicrobial‐resistant pathogen, treatment efforts may be further complicated.2, 3 With the decreasing effectiveness of antimicrobials and suboptimal adherence to certain infection control measures, new and multifaceted prevention strategies are necessary to address the problem of health careassociated infections and antimicrobial resistance.410

One strategy that hospitals can use to reduce the incidence of health careassociated infections and antimicrobial resistance is implementation of quality improvement programs. These programs require clinicians to employ techniques, such as root cause analysis (RCA), which investigates contributing factors to an event to prevent reoccurrence, and healthcare failure mode effects analysis (HFMEA), which applies a systematic method of identifying and preventing problems before they occur.1113 Programs and strategies such as these require leadership and adoption within the hospital. Because of their availability and specialized role in the hospital setting, hospitalists are in a unique position to promote and uphold quality improvement efforts.1417 Professional societies, health care organizations, and governmental agencies can play a role in engaging this group of physicians in improving the quality of patient care in hospitals by providing educational programs and materials.18

In 2004, the Society of Hospital Medicine (SHM) collaborated with the Centers for Disease Control and Prevention (CDC) to develop a quality improvement tool kit to reduce antimicrobial resistance and health careassociated infections. The tool kit was based on the CDC's Campaign to Prevent Antimicrobial Resistance in Healthcare Settings (Campaign), an educational program targeted at clinicians.19 The SHM/CDC tool kit contained campaign materials, a set of slides about quality improvement, worksheets, and additional materials such as infection control policies and guidelines to supplement a 90‐minute workshop consisting of didactic lectures about antimicrobial resistance, quality improvement initiatives, RCA, and HFMEA; a lecture and case study about intravascular catheter‐related infections; and small‐group activity and discussion. The complete toolkit is now available online via the SHM Antimicrobial Resistance Resource Room at http://www.hospitalmedicine.org/AM/Template.cfm?Section=Home&Template=/CM/HTMLDisplay.cfm&ContentID=7542.

The purpose of the workshop was to present the tool kit and increase hospitalists' knowledge and awareness about antimicrobial resistance, health careassociated infections, and quality improvement programs. We assessed the workshop participants' familiarity with the Campaign prior to the workshop, perceptions of antimicrobial resistance, knowledge gained as a result of the workshop, and opinions about the usefulness of the workshop.

METHODS

Data were collected from pretests and posttests administered to participants of one of the SHM workshops in May, June, or July 2005 in Denver, Colorado; Boston, Massachusetts; or Portland, Oregon. One SHM physician leader (D.D.D., coauthor of this article) presented all 3 workshops. The workshops were advertised by SHM using E‐mail to local chapter members. Individual sites used a variety of methods to encourage their hospitalists to attend, and participants were provided a complimentary dinner.

Prior to each workshop, participants completed a 10‐question pretest that had been pilot‐tested by hospitalists in other cities. The pretest assessed demographics; perceptions of the problem of antimicrobial resistance using a Likert scale; familiarity with the Campaign; and knowledge of common infection sites, RCA, HFMEA, and antimicrobial resistance prevention measures.

Immediately following each workshop, a 13‐question posttest was administered to participants. This posttest evaluated the workshop and materials using Likert scales, asked for suggestions for future programming using open‐ended questions, and repeated pretest questions to assess changes in perceptions and knowledge.

Data were entered into an Excel spreadsheet and analyzed using descriptive statistics and t tests to compare pre‐ and posttest changes in knowledge. Likert data assessing perceptions were dichotomized into strongly agree versus all other scale responses. Qualitative open‐ended responses were categorized by theme.

RESULTS

A total of 69 SHM members attended the workshops. Of the 69 participants, 65 completed the pretest, 53 completed the posttest, and 50 completed both the pre‐ and the posttests. Only participants who completed both the pretest and the posttest were included in the analyses (n = 21, Denver; n = 11, Boston; n = 18, Portland). Of the 50 participants who completed both the pre‐ and posttests, 44 (88%) classified themselves as hospitalists in practices ranging from 2 to more than 25 physicians. Participants averaged 9.2 years (range = 1‐27 years) in practice and 4.9 years (range = 1‐10 years) as practicing hospitalists, with no significant differences between the 3 groups. Only 17 participants (34%) were familiar with the Campaign prior to the workshop, and there was no significant variation between the 3 workshops. Those familiar with the Campaign had heard about or received the educational materials from colleagues (n = 5), their facilities (n = 4), professional journals (n = 4), medical conferences (n = 4), or the CDC or SHM websites (n = 4).

Overall, most participants strongly agreed with the statement that antimicrobial resistance was a problem nationally, institutionally, and within their individual practices (Table 1). These perceptions did not significantly differ between the pretest and the posttest. However, statistically significant differences were found when comparing perceptions of the problem of antimicrobial resistance at the national, institutional, and practice levels; more participants strongly agreed that antimicrobial resistance was a problem nationally than within their institutions (pretest, P = .01; posttest, P = .04) or within their practices (pretest, P < .0001; posttest, P = .01).

On the knowledge‐based questions, the overall average test score was 48% on the pretest and 63% on the posttest (P < .0001), with scores varying by question (Table 2). For example, knowledge of quality improvement initiatives/HFMEA was low (an average of 10% correct on the pretest, 48% on the posttest) compared with knowledge about the key prevention strategies from the Campaign to Prevent Antimicrobial Resistance (average of 94% correct on the pretest, 98% on the posttest). Furthermore, scores also varied by workshop location. On the pretest, participants in Boston and Portland scored higher (both 53%) than Denver participants (40%). On the posttest, Portland participants scored the highest (78%) followed by Boston participants (64%) and then Denver participants (50%). Boston and Denver participants differed significantly on pretest knowledge score (P = .04) and Portland and Denver participants differed significantly on posttest knowledge score (P < .0001).

Overall, 43 participants (85%) rated the workshop as either very good or excellent. All but 1 participant (n = 49, 98%) would encourage a colleague to attend the workshop, giving reasons such as that the workshop outlined a major program in delivering good and safe care, offered great information on antimicrobial resistance and methods of quality improvement systems implementation, assisted in find[ing] new tools for improving hospital practice, and addressed a significant factor in hospitals related to morbidity [and] mortality. When asked for general comments about the workshop and suggestions for future improvements, participants requested more direction, more detail, more discussion, specific examples of antimicrobial resistance, and protocols and processes for implementing quality improvement programs. On a scale from 1 (not useful) to 5 (essential), participants rated the usefulness of each workshop segment: intravascular catheter‐related infections lecture and case study (x̄ = 4.3, range = 3‐5), quality improvement initiatives lecture (x̄ = 4.1, range = 2‐5), background on antimicrobial resistance (x̄ = 3.9, range = 2‐5), RCA lecture (x̄ = 3.9, range = 2‐5), HFMEA lecture (x̄ = 3.8, range = 2‐5), and small‐group discussion (x̄ = 3.4, range = 2‐5). These ratings did not vary significantly between the 3 groups.

CONCLUSIONS

To address antimicrobial resistance and health careassociated infections in the hospital setting, the SHM and CDC developed a tool kit and presented a quality improvement workshop to hospitalists in 3 U.S. cities. Overall, the participants scored significantly higher on the knowledge‐based questions on the posttest than on the pretest, indicating that knowledge improved as a result of the workshop. By providing a format that combined didactic lectures with case‐based education, small‐group activities, and discussion, the SHM workshop may have optimized its ability to increase knowledge, similar to the findings in previous research.2021

There were no significant differences between the 3 groups in years of practice, perceptions of the problem, and overall evaluation of the workshop. However, differences were found in knowledge gained as a result of the workshop. For example, the Denver group scored lower on the knowledge‐based questions than did the Boston group on the pretest and the Portland group on the posttest, indicating that knowledge and learning styles may differ by location. These differences may be attributed to variations in hospital environments, hospital‐based educational programs, or medical school and residency training. Differences like these may impact the effectiveness of a program and should be a consideration in the program development process, especially when a program is national in scope, like the CDC's Campaign to Prevent Antimicrobial Resistance in Healthcare Settings. In addition, more than 90% of participants correctly identified key prevention strategies of the Campaign, whereas only 34% were familiar with the Campaign itself prior to the workshop. This result may be a result of the key prevention strategies of the Campaign being derived from well‐established and ‐recognized evidence‐based best practices for patient safety and care.

Although knowledge changed as a result of the workshop, overall perceptions of the problem of antimicrobial resistance did not change significantly from pretest to posttest. It is possible this is because changes in perception require a different or more intensive educational approach. This result also may reflect the initial levels of agreement on the pretest, the measurement instrument itself, and/or the inability to detect differences because of the small number of participants.

Difference did exist in perceptions of the problem of antimicrobial resistance at the national, institutional, and practice levels. Antimicrobial resistance was perceived to be a greater problem on the national level than on the institutional and practice levels. Other studies also have found that clinicians more strongly agree that antimicrobial resistance is a problem nationally than within their institutions and practices.2224 When antimicrobial resistance is not perceived as a problem within institutions and practices, physicians may be less likely to overcome the barriers to following recommended infection prevention guidelines or to implementing quality improvement projects.4 Therefore, educational and intervention efforts like this workshop should address hospitalists' perceptions of the problem of antimicrobial resistance on the individual level as a first step in motivating them to engage in quality improvement.

Although participants' knowledge scores increased from pretest to posttest, gaps in knowledge remained, as indicated by the significantly improved but low overall posttest scores related to RCA and HFMEA. As hospitalists are in a unique position to promote quality improvement programs, these topic areas should be given more attention in future workshops and in training. Furthermore, by adding more specific questions related to each section of the workshop, associations among presentation style, knowledge gained, and perceived usefulness of each section could be evaluated. For example, the participants significantly increased their scores from pretest to posttest on the catheter‐related knowledge‐based question and rated the lecture and case study on intravascular catheter‐related infections as the most useful sections. Future research may explore these possible relationships to better guide selection of presentation styles and topics to ensure that participants gain knowledge and perceive the sections as useful. In addition, by addressing the feedback from participants, such as offering more detail, examples, and discussion, future workshops may have greater perceived usefulness and be better able to increase the knowledge and awareness of quality improvement programs for the prevention of health careassociated infections and antimicrobial resistance.

Although there were 3 workshops conducted in 3 areas across the United States, the sample size at each site was small, and results may not be representative of hospitalists at large. In addition, power calculations should be considered in future studies to increase the ability to better detect differences between and within groups. Another limitation of this study was that the limited data available and participant anonymity meant it was not possible to follow‐up with participants after the workshop to evaluate whether the knowledge they gained was sustained and/or whether they reported changes in practice. However, possession of knowledge and skills to inform practice does not mean that practice will change; therefore, follow‐up is necessary to determine if this workshop was effective in changing behaviors in the long term.25 Although the SHM workshop improved knowledge, more intensive educational strategies may be necessary to affect perceptions and improve the leadership skills required for implementation of quality improvement programs at an institutional level.

Overall, the SHM workshop was found to be a useful tool for increasing knowledge and outlining methods by which hospitalists can lead, coordinate, or participate in measures to prevent infections and improve patient safety. In addition, through the workshop, the SHM and the CDC have provided an example of how professional societies and government agencies can collaborate to address emerging issues in the health care setting.

In the United States, hospitalized patients are at risk of acquiring health careassociated infections that increase morbidity, mortality, length of hospital stay, and cost of care.1 If a health careassociated infection is caused by an antimicrobial‐resistant pathogen, treatment efforts may be further complicated.2, 3 With the decreasing effectiveness of antimicrobials and suboptimal adherence to certain infection control measures, new and multifaceted prevention strategies are necessary to address the problem of health careassociated infections and antimicrobial resistance.410

One strategy that hospitals can use to reduce the incidence of health careassociated infections and antimicrobial resistance is implementation of quality improvement programs. These programs require clinicians to employ techniques, such as root cause analysis (RCA), which investigates contributing factors to an event to prevent reoccurrence, and healthcare failure mode effects analysis (HFMEA), which applies a systematic method of identifying and preventing problems before they occur.1113 Programs and strategies such as these require leadership and adoption within the hospital. Because of their availability and specialized role in the hospital setting, hospitalists are in a unique position to promote and uphold quality improvement efforts.1417 Professional societies, health care organizations, and governmental agencies can play a role in engaging this group of physicians in improving the quality of patient care in hospitals by providing educational programs and materials.18

In 2004, the Society of Hospital Medicine (SHM) collaborated with the Centers for Disease Control and Prevention (CDC) to develop a quality improvement tool kit to reduce antimicrobial resistance and health careassociated infections. The tool kit was based on the CDC's Campaign to Prevent Antimicrobial Resistance in Healthcare Settings (Campaign), an educational program targeted at clinicians.19 The SHM/CDC tool kit contained campaign materials, a set of slides about quality improvement, worksheets, and additional materials such as infection control policies and guidelines to supplement a 90‐minute workshop consisting of didactic lectures about antimicrobial resistance, quality improvement initiatives, RCA, and HFMEA; a lecture and case study about intravascular catheter‐related infections; and small‐group activity and discussion. The complete toolkit is now available online via the SHM Antimicrobial Resistance Resource Room at http://www.hospitalmedicine.org/AM/Template.cfm?Section=Home&Template=/CM/HTMLDisplay.cfm&ContentID=7542.

The purpose of the workshop was to present the tool kit and increase hospitalists' knowledge and awareness about antimicrobial resistance, health careassociated infections, and quality improvement programs. We assessed the workshop participants' familiarity with the Campaign prior to the workshop, perceptions of antimicrobial resistance, knowledge gained as a result of the workshop, and opinions about the usefulness of the workshop.

METHODS

Data were collected from pretests and posttests administered to participants of one of the SHM workshops in May, June, or July 2005 in Denver, Colorado; Boston, Massachusetts; or Portland, Oregon. One SHM physician leader (D.D.D., coauthor of this article) presented all 3 workshops. The workshops were advertised by SHM using E‐mail to local chapter members. Individual sites used a variety of methods to encourage their hospitalists to attend, and participants were provided a complimentary dinner.

Prior to each workshop, participants completed a 10‐question pretest that had been pilot‐tested by hospitalists in other cities. The pretest assessed demographics; perceptions of the problem of antimicrobial resistance using a Likert scale; familiarity with the Campaign; and knowledge of common infection sites, RCA, HFMEA, and antimicrobial resistance prevention measures.

Immediately following each workshop, a 13‐question posttest was administered to participants. This posttest evaluated the workshop and materials using Likert scales, asked for suggestions for future programming using open‐ended questions, and repeated pretest questions to assess changes in perceptions and knowledge.

Data were entered into an Excel spreadsheet and analyzed using descriptive statistics and t tests to compare pre‐ and posttest changes in knowledge. Likert data assessing perceptions were dichotomized into strongly agree versus all other scale responses. Qualitative open‐ended responses were categorized by theme.

RESULTS

A total of 69 SHM members attended the workshops. Of the 69 participants, 65 completed the pretest, 53 completed the posttest, and 50 completed both the pre‐ and the posttests. Only participants who completed both the pretest and the posttest were included in the analyses (n = 21, Denver; n = 11, Boston; n = 18, Portland). Of the 50 participants who completed both the pre‐ and posttests, 44 (88%) classified themselves as hospitalists in practices ranging from 2 to more than 25 physicians. Participants averaged 9.2 years (range = 1‐27 years) in practice and 4.9 years (range = 1‐10 years) as practicing hospitalists, with no significant differences between the 3 groups. Only 17 participants (34%) were familiar with the Campaign prior to the workshop, and there was no significant variation between the 3 workshops. Those familiar with the Campaign had heard about or received the educational materials from colleagues (n = 5), their facilities (n = 4), professional journals (n = 4), medical conferences (n = 4), or the CDC or SHM websites (n = 4).

Overall, most participants strongly agreed with the statement that antimicrobial resistance was a problem nationally, institutionally, and within their individual practices (Table 1). These perceptions did not significantly differ between the pretest and the posttest. However, statistically significant differences were found when comparing perceptions of the problem of antimicrobial resistance at the national, institutional, and practice levels; more participants strongly agreed that antimicrobial resistance was a problem nationally than within their institutions (pretest, P = .01; posttest, P = .04) or within their practices (pretest, P < .0001; posttest, P = .01).

On the knowledge‐based questions, the overall average test score was 48% on the pretest and 63% on the posttest (P < .0001), with scores varying by question (Table 2). For example, knowledge of quality improvement initiatives/HFMEA was low (an average of 10% correct on the pretest, 48% on the posttest) compared with knowledge about the key prevention strategies from the Campaign to Prevent Antimicrobial Resistance (average of 94% correct on the pretest, 98% on the posttest). Furthermore, scores also varied by workshop location. On the pretest, participants in Boston and Portland scored higher (both 53%) than Denver participants (40%). On the posttest, Portland participants scored the highest (78%) followed by Boston participants (64%) and then Denver participants (50%). Boston and Denver participants differed significantly on pretest knowledge score (P = .04) and Portland and Denver participants differed significantly on posttest knowledge score (P < .0001).

Overall, 43 participants (85%) rated the workshop as either very good or excellent. All but 1 participant (n = 49, 98%) would encourage a colleague to attend the workshop, giving reasons such as that the workshop outlined a major program in delivering good and safe care, offered great information on antimicrobial resistance and methods of quality improvement systems implementation, assisted in find[ing] new tools for improving hospital practice, and addressed a significant factor in hospitals related to morbidity [and] mortality. When asked for general comments about the workshop and suggestions for future improvements, participants requested more direction, more detail, more discussion, specific examples of antimicrobial resistance, and protocols and processes for implementing quality improvement programs. On a scale from 1 (not useful) to 5 (essential), participants rated the usefulness of each workshop segment: intravascular catheter‐related infections lecture and case study (x̄ = 4.3, range = 3‐5), quality improvement initiatives lecture (x̄ = 4.1, range = 2‐5), background on antimicrobial resistance (x̄ = 3.9, range = 2‐5), RCA lecture (x̄ = 3.9, range = 2‐5), HFMEA lecture (x̄ = 3.8, range = 2‐5), and small‐group discussion (x̄ = 3.4, range = 2‐5). These ratings did not vary significantly between the 3 groups.

CONCLUSIONS

To address antimicrobial resistance and health careassociated infections in the hospital setting, the SHM and CDC developed a tool kit and presented a quality improvement workshop to hospitalists in 3 U.S. cities. Overall, the participants scored significantly higher on the knowledge‐based questions on the posttest than on the pretest, indicating that knowledge improved as a result of the workshop. By providing a format that combined didactic lectures with case‐based education, small‐group activities, and discussion, the SHM workshop may have optimized its ability to increase knowledge, similar to the findings in previous research.2021

There were no significant differences between the 3 groups in years of practice, perceptions of the problem, and overall evaluation of the workshop. However, differences were found in knowledge gained as a result of the workshop. For example, the Denver group scored lower on the knowledge‐based questions than did the Boston group on the pretest and the Portland group on the posttest, indicating that knowledge and learning styles may differ by location. These differences may be attributed to variations in hospital environments, hospital‐based educational programs, or medical school and residency training. Differences like these may impact the effectiveness of a program and should be a consideration in the program development process, especially when a program is national in scope, like the CDC's Campaign to Prevent Antimicrobial Resistance in Healthcare Settings. In addition, more than 90% of participants correctly identified key prevention strategies of the Campaign, whereas only 34% were familiar with the Campaign itself prior to the workshop. This result may be a result of the key prevention strategies of the Campaign being derived from well‐established and ‐recognized evidence‐based best practices for patient safety and care.

Although knowledge changed as a result of the workshop, overall perceptions of the problem of antimicrobial resistance did not change significantly from pretest to posttest. It is possible this is because changes in perception require a different or more intensive educational approach. This result also may reflect the initial levels of agreement on the pretest, the measurement instrument itself, and/or the inability to detect differences because of the small number of participants.

Difference did exist in perceptions of the problem of antimicrobial resistance at the national, institutional, and practice levels. Antimicrobial resistance was perceived to be a greater problem on the national level than on the institutional and practice levels. Other studies also have found that clinicians more strongly agree that antimicrobial resistance is a problem nationally than within their institutions and practices.2224 When antimicrobial resistance is not perceived as a problem within institutions and practices, physicians may be less likely to overcome the barriers to following recommended infection prevention guidelines or to implementing quality improvement projects.4 Therefore, educational and intervention efforts like this workshop should address hospitalists' perceptions of the problem of antimicrobial resistance on the individual level as a first step in motivating them to engage in quality improvement.

Although participants' knowledge scores increased from pretest to posttest, gaps in knowledge remained, as indicated by the significantly improved but low overall posttest scores related to RCA and HFMEA. As hospitalists are in a unique position to promote quality improvement programs, these topic areas should be given more attention in future workshops and in training. Furthermore, by adding more specific questions related to each section of the workshop, associations among presentation style, knowledge gained, and perceived usefulness of each section could be evaluated. For example, the participants significantly increased their scores from pretest to posttest on the catheter‐related knowledge‐based question and rated the lecture and case study on intravascular catheter‐related infections as the most useful sections. Future research may explore these possible relationships to better guide selection of presentation styles and topics to ensure that participants gain knowledge and perceive the sections as useful. In addition, by addressing the feedback from participants, such as offering more detail, examples, and discussion, future workshops may have greater perceived usefulness and be better able to increase the knowledge and awareness of quality improvement programs for the prevention of health careassociated infections and antimicrobial resistance.

Although there were 3 workshops conducted in 3 areas across the United States, the sample size at each site was small, and results may not be representative of hospitalists at large. In addition, power calculations should be considered in future studies to increase the ability to better detect differences between and within groups. Another limitation of this study was that the limited data available and participant anonymity meant it was not possible to follow‐up with participants after the workshop to evaluate whether the knowledge they gained was sustained and/or whether they reported changes in practice. However, possession of knowledge and skills to inform practice does not mean that practice will change; therefore, follow‐up is necessary to determine if this workshop was effective in changing behaviors in the long term.25 Although the SHM workshop improved knowledge, more intensive educational strategies may be necessary to affect perceptions and improve the leadership skills required for implementation of quality improvement programs at an institutional level.

Overall, the SHM workshop was found to be a useful tool for increasing knowledge and outlining methods by which hospitalists can lead, coordinate, or participate in measures to prevent infections and improve patient safety. In addition, through the workshop, the SHM and the CDC have provided an example of how professional societies and government agencies can collaborate to address emerging issues in the health care setting.

A 58‐year‐old man was evaluated for 3 weeks of leg numbness and weakness. His symptoms began with numbness and tingling in the distal left leg that progressed to weakness that impaired his ability to walk. He had no history of trauma or incontinence but endorsed several months of back pain that worsened when lying flat. He had a history of type 2 diabetes mellitus, hepatitis C infection, hypertension, and posttraumatic stress disorder. He had a remote history of intravenous drug use and had quit tobacco 9 years earlier. Medications he was taking included hydrochlorothiazide, rosiglitazone, oxycodone/acetaminophen, baclofen, ibuprofen, and gabapentin.

Internists see this constellation of complaints frequently in an acute care setting. Finding a unifying diagnosis may be difficult initially, so thinking of the symptoms in series is helpful. The complaint of leg weakness and the pattern of numbness should be further elucidated. Is this true weakness, or is it a feeling of instability because of foot numbness? What is the pattern of the numbness? Peripheral neuropathy typically begins in a symmetric stocking pattern (involving the plantar surface of the feet), then progresses to a glove distribution (involving the hands from the fingers distally to the wrist proximally). Such a pattern in a patient with diabetes would be consistent with distal polyneuropathy, a mixed sensory and motor process. Other possible causes of peripheral neuropathy in this patient include HIV, B12 deficiency, and syphilis. These symptoms could be tied to the back pain if this were intervertebral disk disease, a compression fracture, or a lytic lesion in the vertebrae with resulting nerve impingement or if it were epidural spinal cord compression. The lack of bowel or bladder dysfunction speaks against a cauda equina syndrome but does not rule out more cepahalad spinal pathology.

On neurological examination, I would concentrate on differentiating weakness from pain. I would attempt to determine whether the weakness was of central or peripheral nerve etiology. Helpful findings would include increased tone with upper motor lesions and flaccid tone with lower motor lesions, hyperreflexia with upper motor lesions and hyporeflexia with lower motor lesions, a Babinski sign, muscle atrophy or fasciculations, and gait. A rectal examination would also be helpful to assess for deficits in rectal tone, wink reflex, or saddle anesthesia.

All patients with low back pain who have alarm signs of age older than 50, pain duration of more than 1 month, known cancer, lack of relief with conservative measures, or systemic B symptoms should have imaging of the spine. Although plain films may reveal bony abnormalities, computed tomography (CT) is better for evaluating osseous structures and magnetic resonance imaging (MRI) for evaluating pathology in patients suspected of having an infection or a malignancy. I would obtain imaging of the spine in this patient.

The patient was receiving care at an outside clinic for 2 liver lesions discovered on abdominal ultrasound 19 months prior to admission. CT showed that the lesions were 4.0 and 2.3 cm in diameter 17 months prior to admission and 5.0 and 3.0 cm in diameter 5 months prior to admission. No cirrhosis was appreciated on the ultrasound or CT. The patient was referred for CT‐guided biopsy of the larger mass after the second CT, but he became anxious and left before the biopsy was obtained.

This piece of the history is ominous, as it increases the possibility of cancer in our differential. Metastatic disease could provide a unifying diagnosis, explaining the constellation of back pain, leg weakness, and liver lesions. Lung cancer commonly metastasizes to the liver and to bone, so I would obtain a chest x‐ray. Other possible types of cancer in this situation include cancer of the prostate, colon, or thyroid and melanoma. In this patient, who has hepatitis C, hepatocellular carcinoma (HCC) could be the primary etiology, although cirrhosis was not seen on CT and HCC metastasizes to the spine less commonly than do other primary cancers (eg, lung, breast, prostate). Nonetheless, I would obtain an alpha‐fetoprotein level, which would confirm HCC in a patient with liver lesions if it was greater than 200 g/L. Pancreatic cancer has been associated with both type 2 diabetes and liver lesions and could explain his abdominal pain.

There is no comment on the arterial‐phase CT imaging of the liver lesions. Dual‐phase CT scans examine the hepatic arterial and portal vein phases of contrast filling. Triple‐phase CT scans also examine the portal vein influx phase. Both hemangiomas and hypervascular HCCs enhance on the arterial phase, as they derive their blood flow from the hepatic artery. Therefore, arterial‐phase imaging can help to distinguish vascular tumors that flush with contrast, such as hemangiomas, melanoma, and HCC, from less vascular tumors such as pancreatic and colon cancer. Other liver lesions such as focal nodular hyperplasia and adenomas cannot be excluded in this situation as they also may enhance during the arterial phase and can grow over time, as this patient's repeat imaging documented. It seems unlikely that this patient has a liver abscess because he has a paucity of constitutional symptoms and no travel history. The liver lesions seen on initial imaging were larger than 1.0 cm, so I would have favored an earlier biopsy to obtain a tissue diagnosis.

The patient was afebrile, and all other vital signs were normal. He appeared well nourished and anicteric. There was no lymphadenopathy. Cardiac auscultation was regular without murmurs. The lungs were clear. The abdomen was without fluid wave or hepatosplenomegaly and was tender to palpation in the right upper and lower quadrants. There was no midline tenderness to palpation of the spine.

Cranial nerves II‐XII were intact. Lower extremity muscle tone could not be accurately assessed due to splinting from back pain. Strength was 3 of 5 in the left hip extensors and left knee flexors and extensors, and 1 of 5 in the left hip flexors. He had no motor strength in the distal left lower extremity extensors. Bilateral upper extremity and right leg strength were normal. Sensation to light touch, temperature, and pain was decreased circumferentially below the xiphoid. The patient had hyperesthesia in a band around the thorax just above the xiphoid and paresthesia of the perineal area. Left patellar tendon reflexes were brisk, and left ankle jerk was absent, but other reflexes were normal. Toes were down‐going bilaterally. The anal wink was absent, and rectal tone was decreased. Results of the cerebellar exam were normal. Gait could not be assessed.

The results of the exam are notable for not showing the stigmata of end‐stage liver disease. The results of the neurological exam are concerning, with decreased sensation at approximately the T7 level that is almost certainly a result of epidural compression of the spinal cord. Hematogenous metastasis to the vertebrae from one of the tumors mentioned above, with spread into the thecal sac, is the most likely culprit. An epidural abscess is possible because the patient has diabetes and a history of injection drug use.

The thoracic spine is involved in 60% of spinal cord metastases. This patient's left‐sided distal leg weakness is consistent with having corticospinal tract compression and indicates thoracic spine involvement. Flaccid paralysis is classically found in lower motor neuron weakness, but is also seen in the early stages of upper motor neuron pathology. Lesions found above the cauda equina often spare the perineal area, but low thoracic lesions involving the conus medullaris (from T10 to L1) could explain both his loss of anal wink and his decreased rectal tone.

This patient's presentation is unfortunately classic for epidural spinal cord compression. Because the onset of compression is insidious, the diagnosis is often delayed, even in patients with known cancer. Urgent imaging is imperative to evaluate this possibility, as having any meaningful chance of recovery of function depends on rapid relief of the spinal cord compression. I would obtain an emergent MRI of the thoracic and lumbosacral spine.

Laboratory studies showed the following: hemoglobin, 13.1 g/dL; mean corpuscular volume, 80 m³; platelet count, 149,000/L; creatinine, 1.9 mg/dL; aspartate aminotransferase, 66 U/L (5‐35 U/L); alanine aminotransferase, 66 U/L (7‐56 U/L); alkaline phosphatase, 87 U/L (40‐125 U/L); total bilirubin, 1.3 mg/dL; prostate specific antigen (PSA), 1.6 g/dL; and alpha‐fetoprotein (AFP), 10.3 g/L. White cell count, sodium, glucose, calcium, and albumin levels, and prothrombin and partial‐thromboplastin times were within normal ranges.

His liver function tests likely reflect chronic hepatitis C infection. His renal insufficiency could be a result of hypertension, diabetes, or dehydration given that he has been bed‐bound.

Most intriguing are the normal PSA level and only slightly elevated AFP level. PSA is useful for detecting recurrence of prostate cancer or following response of therapy, but the utility of PSA as a screening tool remains controversial in part because of its low specificity. Prostate cancer is the most commonly diagnosed cancer among men and cannot be ruled out by a normal PSA. In a patient with hepatitis C, cirrhosis (which we have not conclusively diagnosed), and a radiologically suspicious liver lesion, an AFP > 200 g/L would be diagnostic of HCC. In this case, however, mildly elevated AFP does not help us to either diagnose or exclude HCC.

The chest x‐ray showed no abnormalities. MRI of the spine revealed lytic lesions in the T7‐T10 vertebral bodies with spinal cord compression at the T7 level (Fig. 1).

Figure 1

A repeat CT scan of the abdomen showed a coarse, nodular liver with 2 heterogeneous, early‐enhancing masses (4.7 4.2 and 3.4 2.4 cm in diameter) with surrounding satellite lesions (Fig. 2).

Figure 2

The enhancement pattern on dual‐phase liver protocol CT was not characteristic of HCC. The left portal vein was not visualized. Splenomegaly and esophageal varices were observed. The adrenal glands showed bilateral, heterogeneous enhancing masses. The epiphrenic, retroperitoneal, and periportal lymph nodes were enlarged. Lytic lesions were seen in the sacrum, left iliac wing, and T7‐T10 vertebral bodies.

Intravenous high‐dose steroids were started. The neurosurgery team advised that no surgical interventions were appropriate because of the patient's poor functional status and the extent of his disease.

It is unfortunate that no neurosurgical interventions could help this patient, especially because we are not yet sure of the final diagnosis. Standard indications for neurosurgical decompression include compression from bone fragments, spinal instability requiring fixation, and lack of response to radiation therapy. Patients must also be able to tolerate surgery. Although evidence supports the use of corticosteroids in reducing edema, inflammation, and neurological deficits in malignant spinal cord compression, there is not consensus on what the optimal dose is. Doses of 16‐100 mg of dexamethasone per day appear to be beneficial, as long as higher doses are rapidly tapered to avoid toxic effects. High‐dose steroids minimize the initial edema but are unlikely to change the long‐term outcome of patients who are nonambulatory on arrival.

The CT scan does not help us distinguish between metastatic cancer and primary HCC. Adrenal metastases are very uncommon in HCC. Lung cancer, however, metastasizes to the liver, adrenal glands, and spine, even without significant pulmonary symptoms. HCC may be seen on CT as a solitary mass, a dominant mass with surrounding satellite lesions, multifocal lesions, or a diffusely infiltrating tumor. This diagnosis now seems more likely given the finding of cirrhosis, which increases the risk of HCC in individuals with hepatitis C infection.

We need to obtain tissue for diagnosis and prognosis and to guide therapy. I would consult with radiology and gastroenterology colleagues about the best location to biopsy, but a bone biopsy should be avoided because the pathologic yield is lower.

The radiology and gastroenterology consultants recommended adrenal biopsy because there was easier posterior access for tissue. A liver biopsy was avoided because of the risk of bleeding with hypervascular masses. Fine‐needle aspiration of the mass in the right adrenal gland was performed. The pathology demonstrated bile production and hexagonal arrangement of cells with endothelial cuffing consistent with hepatocellular carcinoma. The oncology staff was consulted about palliative chemotherapy options. The patient began radiation therapy directed at the T7 lesion compressing the spinal cord. He regained minimal movement of his foot. After discussing treatment options with the oncology staff, the patient declined chemotherapy and was transitioned to hospice, where he died 3 weeks later.

COMMENTARY

Hepatocellular carcinoma (HCC) is the third‐leading cause of cancer death and the fifth‐leading cause of cancer worldwide. It causes nearly 1 million deaths annually, and unlike many other cancers, its incidence and mortality rate are rising. Most cases of HCC in Africa and Asia are a result of chronic hepatitis B infection, but in the United States HCC is primarily attributable to hepatitis C infection.1 The annual incidence of HCC in the U.S. population, now about 4 cases per 100,000 people,2 is rising because of the increased prevalence of hepatitis C. Other causes of HCC, such as alcoholic liver disease, hepatitis B infection, and hemochromatosis, have remained stable and have not contributed as significantly to the rising incidence of HCC. For the individual patient, hepatitis C infection conveys a 20‐fold increase in the risk for HCC (2%‐8% risk/year).1 Eighty percent of cases of HCC develop in patients with cirrhosis.3 Unlike patients with hepatitis B infection, persons chronically infected with hepatitis C rarely develop HCC unless they have cirrhosis.

The American Association for the Study of Liver Disease recommends that hepatitis Binfected individuals at high risk for HCC (eg, men older than 40 years and persons with cirrhosis or a family history of HCC) and hepatitis Cinfected individuals with cirrhosis4 be periodically screened for HCC with alpha‐fetoprotein (AFP) and ultrasonography (every 6 months to approximate the doubling time of the tumor5). Using the most commonly reported cutoff for a positive test result for hepatocellular carcinoma (AFP level > 20 g/L) resulted in the following test characteristics: sensitivity, 41%‐65%; specificity, 80%‐94%; positive likelihood ratio, 3.1‐6.8; and negative likelihood ratio, 0.4‐0.6.6 AFP alone is therefore a poor screening test for HCC, and as shown in this case, AFP levels can be normal or only minimally elevated in the setting of diffusely metastatic disease. Ultrasonography alone is only 35%‐87% sensitive in detecting HCC,79 but the combination of AFP and ultrasonography identified 100% of the HCC cases in one small case series.10

For the patient in this case, the optimal clinical pathway would have been to transition from screening to diagnostic measures in a timely manner. Consensus guidelines from the European Association for Study of the Liver in 2001 recommend biopsy of all focal liver lesions that are between 1 and 2 cm.11 The American Association for the Study of Liver Diseases (AASLD) recommends that focal liver lesions between 1 and 2 cm found on ultrasound in cirrhotic livers be followed by 2 dynamic studies: CT, MRI, or contrast ultrasound. If 2 separate studies reveal typical characteristics of HCC, then the lesion should be treated as HCC, and if not typical, then the lesion should be biopsied.4 Although no studies were available to support the recommendations, both the EASL and AASLD advise that lesions greater than 2 cm with demonstrated vascularity on both ultrasonography and CT can be diagnosed as HCC without biopsy and that lesions smaller than 1 cm be monitored.4, 11

Hepatocellular carcinoma can metastasize to almost anywhere in the body by hematologic or lymphatic spread or by direct extension. The most common site for metastases of HCC is the lung. Metastases to the lung arise primarily from arterial emboli and therefore are most common in the lower lobes, where there is greater perfusion.12 The second most common site is intraabdominal lymph nodes. The axial skeleton is the third most common site of metastases and, as in this case, primarily involves the spine.13 Other sites of metastases include the peritoneum, the inferior vena cava and right atrium by direct extension, and, less commonly, the gallbladder and spleen. Autopsy studies of patients with HCC found that 8% had metastases to the adrenal glands, as did this patient.13 Metastasis to the central nervous system is rare.

There were several challenging aspects of this case, including atypical radiologic appearance, an unusual metastatic pattern, and minimally elevated AFP level. This case raises 3 key points that we must remember as clinicians:

• 1

  Patients infected with hepatitis C who are found to have suspicious hepatic lesions should be aggressively evaluated for HCC.

• 2

  Using an AFP level < 20 g/L as a screening test is not helpful because this level can be seen even with widely metastatic disease.

• 3

  Knowledge of available screening tests as well as the many possible manifestations of HCC helps clinicians to diagnose HCC earlier, when the disease is potentially curable.

A 58‐year‐old man was evaluated for 3 weeks of leg numbness and weakness. His symptoms began with numbness and tingling in the distal left leg that progressed to weakness that impaired his ability to walk. He had no history of trauma or incontinence but endorsed several months of back pain that worsened when lying flat. He had a history of type 2 diabetes mellitus, hepatitis C infection, hypertension, and posttraumatic stress disorder. He had a remote history of intravenous drug use and had quit tobacco 9 years earlier. Medications he was taking included hydrochlorothiazide, rosiglitazone, oxycodone/acetaminophen, baclofen, ibuprofen, and gabapentin.

Internists see this constellation of complaints frequently in an acute care setting. Finding a unifying diagnosis may be difficult initially, so thinking of the symptoms in series is helpful. The complaint of leg weakness and the pattern of numbness should be further elucidated. Is this true weakness, or is it a feeling of instability because of foot numbness? What is the pattern of the numbness? Peripheral neuropathy typically begins in a symmetric stocking pattern (involving the plantar surface of the feet), then progresses to a glove distribution (involving the hands from the fingers distally to the wrist proximally). Such a pattern in a patient with diabetes would be consistent with distal polyneuropathy, a mixed sensory and motor process. Other possible causes of peripheral neuropathy in this patient include HIV, B12 deficiency, and syphilis. These symptoms could be tied to the back pain if this were intervertebral disk disease, a compression fracture, or a lytic lesion in the vertebrae with resulting nerve impingement or if it were epidural spinal cord compression. The lack of bowel or bladder dysfunction speaks against a cauda equina syndrome but does not rule out more cepahalad spinal pathology.

On neurological examination, I would concentrate on differentiating weakness from pain. I would attempt to determine whether the weakness was of central or peripheral nerve etiology. Helpful findings would include increased tone with upper motor lesions and flaccid tone with lower motor lesions, hyperreflexia with upper motor lesions and hyporeflexia with lower motor lesions, a Babinski sign, muscle atrophy or fasciculations, and gait. A rectal examination would also be helpful to assess for deficits in rectal tone, wink reflex, or saddle anesthesia.

All patients with low back pain who have alarm signs of age older than 50, pain duration of more than 1 month, known cancer, lack of relief with conservative measures, or systemic B symptoms should have imaging of the spine. Although plain films may reveal bony abnormalities, computed tomography (CT) is better for evaluating osseous structures and magnetic resonance imaging (MRI) for evaluating pathology in patients suspected of having an infection or a malignancy. I would obtain imaging of the spine in this patient.

The patient was receiving care at an outside clinic for 2 liver lesions discovered on abdominal ultrasound 19 months prior to admission. CT showed that the lesions were 4.0 and 2.3 cm in diameter 17 months prior to admission and 5.0 and 3.0 cm in diameter 5 months prior to admission. No cirrhosis was appreciated on the ultrasound or CT. The patient was referred for CT‐guided biopsy of the larger mass after the second CT, but he became anxious and left before the biopsy was obtained.

This piece of the history is ominous, as it increases the possibility of cancer in our differential. Metastatic disease could provide a unifying diagnosis, explaining the constellation of back pain, leg weakness, and liver lesions. Lung cancer commonly metastasizes to the liver and to bone, so I would obtain a chest x‐ray. Other possible types of cancer in this situation include cancer of the prostate, colon, or thyroid and melanoma. In this patient, who has hepatitis C, hepatocellular carcinoma (HCC) could be the primary etiology, although cirrhosis was not seen on CT and HCC metastasizes to the spine less commonly than do other primary cancers (eg, lung, breast, prostate). Nonetheless, I would obtain an alpha‐fetoprotein level, which would confirm HCC in a patient with liver lesions if it was greater than 200 g/L. Pancreatic cancer has been associated with both type 2 diabetes and liver lesions and could explain his abdominal pain.

There is no comment on the arterial‐phase CT imaging of the liver lesions. Dual‐phase CT scans examine the hepatic arterial and portal vein phases of contrast filling. Triple‐phase CT scans also examine the portal vein influx phase. Both hemangiomas and hypervascular HCCs enhance on the arterial phase, as they derive their blood flow from the hepatic artery. Therefore, arterial‐phase imaging can help to distinguish vascular tumors that flush with contrast, such as hemangiomas, melanoma, and HCC, from less vascular tumors such as pancreatic and colon cancer. Other liver lesions such as focal nodular hyperplasia and adenomas cannot be excluded in this situation as they also may enhance during the arterial phase and can grow over time, as this patient's repeat imaging documented. It seems unlikely that this patient has a liver abscess because he has a paucity of constitutional symptoms and no travel history. The liver lesions seen on initial imaging were larger than 1.0 cm, so I would have favored an earlier biopsy to obtain a tissue diagnosis.

The patient was afebrile, and all other vital signs were normal. He appeared well nourished and anicteric. There was no lymphadenopathy. Cardiac auscultation was regular without murmurs. The lungs were clear. The abdomen was without fluid wave or hepatosplenomegaly and was tender to palpation in the right upper and lower quadrants. There was no midline tenderness to palpation of the spine.

Cranial nerves II‐XII were intact. Lower extremity muscle tone could not be accurately assessed due to splinting from back pain. Strength was 3 of 5 in the left hip extensors and left knee flexors and extensors, and 1 of 5 in the left hip flexors. He had no motor strength in the distal left lower extremity extensors. Bilateral upper extremity and right leg strength were normal. Sensation to light touch, temperature, and pain was decreased circumferentially below the xiphoid. The patient had hyperesthesia in a band around the thorax just above the xiphoid and paresthesia of the perineal area. Left patellar tendon reflexes were brisk, and left ankle jerk was absent, but other reflexes were normal. Toes were down‐going bilaterally. The anal wink was absent, and rectal tone was decreased. Results of the cerebellar exam were normal. Gait could not be assessed.

The results of the exam are notable for not showing the stigmata of end‐stage liver disease. The results of the neurological exam are concerning, with decreased sensation at approximately the T7 level that is almost certainly a result of epidural compression of the spinal cord. Hematogenous metastasis to the vertebrae from one of the tumors mentioned above, with spread into the thecal sac, is the most likely culprit. An epidural abscess is possible because the patient has diabetes and a history of injection drug use.

The thoracic spine is involved in 60% of spinal cord metastases. This patient's left‐sided distal leg weakness is consistent with having corticospinal tract compression and indicates thoracic spine involvement. Flaccid paralysis is classically found in lower motor neuron weakness, but is also seen in the early stages of upper motor neuron pathology. Lesions found above the cauda equina often spare the perineal area, but low thoracic lesions involving the conus medullaris (from T10 to L1) could explain both his loss of anal wink and his decreased rectal tone.

This patient's presentation is unfortunately classic for epidural spinal cord compression. Because the onset of compression is insidious, the diagnosis is often delayed, even in patients with known cancer. Urgent imaging is imperative to evaluate this possibility, as having any meaningful chance of recovery of function depends on rapid relief of the spinal cord compression. I would obtain an emergent MRI of the thoracic and lumbosacral spine.

Laboratory studies showed the following: hemoglobin, 13.1 g/dL; mean corpuscular volume, 80 m³; platelet count, 149,000/L; creatinine, 1.9 mg/dL; aspartate aminotransferase, 66 U/L (5‐35 U/L); alanine aminotransferase, 66 U/L (7‐56 U/L); alkaline phosphatase, 87 U/L (40‐125 U/L); total bilirubin, 1.3 mg/dL; prostate specific antigen (PSA), 1.6 g/dL; and alpha‐fetoprotein (AFP), 10.3 g/L. White cell count, sodium, glucose, calcium, and albumin levels, and prothrombin and partial‐thromboplastin times were within normal ranges.

His liver function tests likely reflect chronic hepatitis C infection. His renal insufficiency could be a result of hypertension, diabetes, or dehydration given that he has been bed‐bound.

Most intriguing are the normal PSA level and only slightly elevated AFP level. PSA is useful for detecting recurrence of prostate cancer or following response of therapy, but the utility of PSA as a screening tool remains controversial in part because of its low specificity. Prostate cancer is the most commonly diagnosed cancer among men and cannot be ruled out by a normal PSA. In a patient with hepatitis C, cirrhosis (which we have not conclusively diagnosed), and a radiologically suspicious liver lesion, an AFP > 200 g/L would be diagnostic of HCC. In this case, however, mildly elevated AFP does not help us to either diagnose or exclude HCC.

The chest x‐ray showed no abnormalities. MRI of the spine revealed lytic lesions in the T7‐T10 vertebral bodies with spinal cord compression at the T7 level (Fig. 1).

Figure 1

A repeat CT scan of the abdomen showed a coarse, nodular liver with 2 heterogeneous, early‐enhancing masses (4.7 4.2 and 3.4 2.4 cm in diameter) with surrounding satellite lesions (Fig. 2).

Figure 2

The enhancement pattern on dual‐phase liver protocol CT was not characteristic of HCC. The left portal vein was not visualized. Splenomegaly and esophageal varices were observed. The adrenal glands showed bilateral, heterogeneous enhancing masses. The epiphrenic, retroperitoneal, and periportal lymph nodes were enlarged. Lytic lesions were seen in the sacrum, left iliac wing, and T7‐T10 vertebral bodies.

Intravenous high‐dose steroids were started. The neurosurgery team advised that no surgical interventions were appropriate because of the patient's poor functional status and the extent of his disease.

It is unfortunate that no neurosurgical interventions could help this patient, especially because we are not yet sure of the final diagnosis. Standard indications for neurosurgical decompression include compression from bone fragments, spinal instability requiring fixation, and lack of response to radiation therapy. Patients must also be able to tolerate surgery. Although evidence supports the use of corticosteroids in reducing edema, inflammation, and neurological deficits in malignant spinal cord compression, there is not consensus on what the optimal dose is. Doses of 16‐100 mg of dexamethasone per day appear to be beneficial, as long as higher doses are rapidly tapered to avoid toxic effects. High‐dose steroids minimize the initial edema but are unlikely to change the long‐term outcome of patients who are nonambulatory on arrival.

The CT scan does not help us distinguish between metastatic cancer and primary HCC. Adrenal metastases are very uncommon in HCC. Lung cancer, however, metastasizes to the liver, adrenal glands, and spine, even without significant pulmonary symptoms. HCC may be seen on CT as a solitary mass, a dominant mass with surrounding satellite lesions, multifocal lesions, or a diffusely infiltrating tumor. This diagnosis now seems more likely given the finding of cirrhosis, which increases the risk of HCC in individuals with hepatitis C infection.

We need to obtain tissue for diagnosis and prognosis and to guide therapy. I would consult with radiology and gastroenterology colleagues about the best location to biopsy, but a bone biopsy should be avoided because the pathologic yield is lower.

The radiology and gastroenterology consultants recommended adrenal biopsy because there was easier posterior access for tissue. A liver biopsy was avoided because of the risk of bleeding with hypervascular masses. Fine‐needle aspiration of the mass in the right adrenal gland was performed. The pathology demonstrated bile production and hexagonal arrangement of cells with endothelial cuffing consistent with hepatocellular carcinoma. The oncology staff was consulted about palliative chemotherapy options. The patient began radiation therapy directed at the T7 lesion compressing the spinal cord. He regained minimal movement of his foot. After discussing treatment options with the oncology staff, the patient declined chemotherapy and was transitioned to hospice, where he died 3 weeks later.

COMMENTARY

Hepatocellular carcinoma (HCC) is the third‐leading cause of cancer death and the fifth‐leading cause of cancer worldwide. It causes nearly 1 million deaths annually, and unlike many other cancers, its incidence and mortality rate are rising. Most cases of HCC in Africa and Asia are a result of chronic hepatitis B infection, but in the United States HCC is primarily attributable to hepatitis C infection.1 The annual incidence of HCC in the U.S. population, now about 4 cases per 100,000 people,2 is rising because of the increased prevalence of hepatitis C. Other causes of HCC, such as alcoholic liver disease, hepatitis B infection, and hemochromatosis, have remained stable and have not contributed as significantly to the rising incidence of HCC. For the individual patient, hepatitis C infection conveys a 20‐fold increase in the risk for HCC (2%‐8% risk/year).1 Eighty percent of cases of HCC develop in patients with cirrhosis.3 Unlike patients with hepatitis B infection, persons chronically infected with hepatitis C rarely develop HCC unless they have cirrhosis.

The American Association for the Study of Liver Disease recommends that hepatitis Binfected individuals at high risk for HCC (eg, men older than 40 years and persons with cirrhosis or a family history of HCC) and hepatitis Cinfected individuals with cirrhosis4 be periodically screened for HCC with alpha‐fetoprotein (AFP) and ultrasonography (every 6 months to approximate the doubling time of the tumor5). Using the most commonly reported cutoff for a positive test result for hepatocellular carcinoma (AFP level > 20 g/L) resulted in the following test characteristics: sensitivity, 41%‐65%; specificity, 80%‐94%; positive likelihood ratio, 3.1‐6.8; and negative likelihood ratio, 0.4‐0.6.6 AFP alone is therefore a poor screening test for HCC, and as shown in this case, AFP levels can be normal or only minimally elevated in the setting of diffusely metastatic disease. Ultrasonography alone is only 35%‐87% sensitive in detecting HCC,79 but the combination of AFP and ultrasonography identified 100% of the HCC cases in one small case series.10

For the patient in this case, the optimal clinical pathway would have been to transition from screening to diagnostic measures in a timely manner. Consensus guidelines from the European Association for Study of the Liver in 2001 recommend biopsy of all focal liver lesions that are between 1 and 2 cm.11 The American Association for the Study of Liver Diseases (AASLD) recommends that focal liver lesions between 1 and 2 cm found on ultrasound in cirrhotic livers be followed by 2 dynamic studies: CT, MRI, or contrast ultrasound. If 2 separate studies reveal typical characteristics of HCC, then the lesion should be treated as HCC, and if not typical, then the lesion should be biopsied.4 Although no studies were available to support the recommendations, both the EASL and AASLD advise that lesions greater than 2 cm with demonstrated vascularity on both ultrasonography and CT can be diagnosed as HCC without biopsy and that lesions smaller than 1 cm be monitored.4, 11

Hepatocellular carcinoma can metastasize to almost anywhere in the body by hematologic or lymphatic spread or by direct extension. The most common site for metastases of HCC is the lung. Metastases to the lung arise primarily from arterial emboli and therefore are most common in the lower lobes, where there is greater perfusion.12 The second most common site is intraabdominal lymph nodes. The axial skeleton is the third most common site of metastases and, as in this case, primarily involves the spine.13 Other sites of metastases include the peritoneum, the inferior vena cava and right atrium by direct extension, and, less commonly, the gallbladder and spleen. Autopsy studies of patients with HCC found that 8% had metastases to the adrenal glands, as did this patient.13 Metastasis to the central nervous system is rare.

There were several challenging aspects of this case, including atypical radiologic appearance, an unusual metastatic pattern, and minimally elevated AFP level. This case raises 3 key points that we must remember as clinicians:

• 1

  Patients infected with hepatitis C who are found to have suspicious hepatic lesions should be aggressively evaluated for HCC.

• 2

  Using an AFP level < 20 g/L as a screening test is not helpful because this level can be seen even with widely metastatic disease.

• 3

  Knowledge of available screening tests as well as the many possible manifestations of HCC helps clinicians to diagnose HCC earlier, when the disease is potentially curable.

A 58‐year‐old man was evaluated for 3 weeks of leg numbness and weakness. His symptoms began with numbness and tingling in the distal left leg that progressed to weakness that impaired his ability to walk. He had no history of trauma or incontinence but endorsed several months of back pain that worsened when lying flat. He had a history of type 2 diabetes mellitus, hepatitis C infection, hypertension, and posttraumatic stress disorder. He had a remote history of intravenous drug use and had quit tobacco 9 years earlier. Medications he was taking included hydrochlorothiazide, rosiglitazone, oxycodone/acetaminophen, baclofen, ibuprofen, and gabapentin.

Internists see this constellation of complaints frequently in an acute care setting. Finding a unifying diagnosis may be difficult initially, so thinking of the symptoms in series is helpful. The complaint of leg weakness and the pattern of numbness should be further elucidated. Is this true weakness, or is it a feeling of instability because of foot numbness? What is the pattern of the numbness? Peripheral neuropathy typically begins in a symmetric stocking pattern (involving the plantar surface of the feet), then progresses to a glove distribution (involving the hands from the fingers distally to the wrist proximally). Such a pattern in a patient with diabetes would be consistent with distal polyneuropathy, a mixed sensory and motor process. Other possible causes of peripheral neuropathy in this patient include HIV, B12 deficiency, and syphilis. These symptoms could be tied to the back pain if this were intervertebral disk disease, a compression fracture, or a lytic lesion in the vertebrae with resulting nerve impingement or if it were epidural spinal cord compression. The lack of bowel or bladder dysfunction speaks against a cauda equina syndrome but does not rule out more cepahalad spinal pathology.

On neurological examination, I would concentrate on differentiating weakness from pain. I would attempt to determine whether the weakness was of central or peripheral nerve etiology. Helpful findings would include increased tone with upper motor lesions and flaccid tone with lower motor lesions, hyperreflexia with upper motor lesions and hyporeflexia with lower motor lesions, a Babinski sign, muscle atrophy or fasciculations, and gait. A rectal examination would also be helpful to assess for deficits in rectal tone, wink reflex, or saddle anesthesia.

All patients with low back pain who have alarm signs of age older than 50, pain duration of more than 1 month, known cancer, lack of relief with conservative measures, or systemic B symptoms should have imaging of the spine. Although plain films may reveal bony abnormalities, computed tomography (CT) is better for evaluating osseous structures and magnetic resonance imaging (MRI) for evaluating pathology in patients suspected of having an infection or a malignancy. I would obtain imaging of the spine in this patient.

The patient was receiving care at an outside clinic for 2 liver lesions discovered on abdominal ultrasound 19 months prior to admission. CT showed that the lesions were 4.0 and 2.3 cm in diameter 17 months prior to admission and 5.0 and 3.0 cm in diameter 5 months prior to admission. No cirrhosis was appreciated on the ultrasound or CT. The patient was referred for CT‐guided biopsy of the larger mass after the second CT, but he became anxious and left before the biopsy was obtained.

This piece of the history is ominous, as it increases the possibility of cancer in our differential. Metastatic disease could provide a unifying diagnosis, explaining the constellation of back pain, leg weakness, and liver lesions. Lung cancer commonly metastasizes to the liver and to bone, so I would obtain a chest x‐ray. Other possible types of cancer in this situation include cancer of the prostate, colon, or thyroid and melanoma. In this patient, who has hepatitis C, hepatocellular carcinoma (HCC) could be the primary etiology, although cirrhosis was not seen on CT and HCC metastasizes to the spine less commonly than do other primary cancers (eg, lung, breast, prostate). Nonetheless, I would obtain an alpha‐fetoprotein level, which would confirm HCC in a patient with liver lesions if it was greater than 200 g/L. Pancreatic cancer has been associated with both type 2 diabetes and liver lesions and could explain his abdominal pain.

There is no comment on the arterial‐phase CT imaging of the liver lesions. Dual‐phase CT scans examine the hepatic arterial and portal vein phases of contrast filling. Triple‐phase CT scans also examine the portal vein influx phase. Both hemangiomas and hypervascular HCCs enhance on the arterial phase, as they derive their blood flow from the hepatic artery. Therefore, arterial‐phase imaging can help to distinguish vascular tumors that flush with contrast, such as hemangiomas, melanoma, and HCC, from less vascular tumors such as pancreatic and colon cancer. Other liver lesions such as focal nodular hyperplasia and adenomas cannot be excluded in this situation as they also may enhance during the arterial phase and can grow over time, as this patient's repeat imaging documented. It seems unlikely that this patient has a liver abscess because he has a paucity of constitutional symptoms and no travel history. The liver lesions seen on initial imaging were larger than 1.0 cm, so I would have favored an earlier biopsy to obtain a tissue diagnosis.

The patient was afebrile, and all other vital signs were normal. He appeared well nourished and anicteric. There was no lymphadenopathy. Cardiac auscultation was regular without murmurs. The lungs were clear. The abdomen was without fluid wave or hepatosplenomegaly and was tender to palpation in the right upper and lower quadrants. There was no midline tenderness to palpation of the spine.

Cranial nerves II‐XII were intact. Lower extremity muscle tone could not be accurately assessed due to splinting from back pain. Strength was 3 of 5 in the left hip extensors and left knee flexors and extensors, and 1 of 5 in the left hip flexors. He had no motor strength in the distal left lower extremity extensors. Bilateral upper extremity and right leg strength were normal. Sensation to light touch, temperature, and pain was decreased circumferentially below the xiphoid. The patient had hyperesthesia in a band around the thorax just above the xiphoid and paresthesia of the perineal area. Left patellar tendon reflexes were brisk, and left ankle jerk was absent, but other reflexes were normal. Toes were down‐going bilaterally. The anal wink was absent, and rectal tone was decreased. Results of the cerebellar exam were normal. Gait could not be assessed.

The results of the exam are notable for not showing the stigmata of end‐stage liver disease. The results of the neurological exam are concerning, with decreased sensation at approximately the T7 level that is almost certainly a result of epidural compression of the spinal cord. Hematogenous metastasis to the vertebrae from one of the tumors mentioned above, with spread into the thecal sac, is the most likely culprit. An epidural abscess is possible because the patient has diabetes and a history of injection drug use.

The thoracic spine is involved in 60% of spinal cord metastases. This patient's left‐sided distal leg weakness is consistent with having corticospinal tract compression and indicates thoracic spine involvement. Flaccid paralysis is classically found in lower motor neuron weakness, but is also seen in the early stages of upper motor neuron pathology. Lesions found above the cauda equina often spare the perineal area, but low thoracic lesions involving the conus medullaris (from T10 to L1) could explain both his loss of anal wink and his decreased rectal tone.

This patient's presentation is unfortunately classic for epidural spinal cord compression. Because the onset of compression is insidious, the diagnosis is often delayed, even in patients with known cancer. Urgent imaging is imperative to evaluate this possibility, as having any meaningful chance of recovery of function depends on rapid relief of the spinal cord compression. I would obtain an emergent MRI of the thoracic and lumbosacral spine.

Laboratory studies showed the following: hemoglobin, 13.1 g/dL; mean corpuscular volume, 80 m³; platelet count, 149,000/L; creatinine, 1.9 mg/dL; aspartate aminotransferase, 66 U/L (5‐35 U/L); alanine aminotransferase, 66 U/L (7‐56 U/L); alkaline phosphatase, 87 U/L (40‐125 U/L); total bilirubin, 1.3 mg/dL; prostate specific antigen (PSA), 1.6 g/dL; and alpha‐fetoprotein (AFP), 10.3 g/L. White cell count, sodium, glucose, calcium, and albumin levels, and prothrombin and partial‐thromboplastin times were within normal ranges.

His liver function tests likely reflect chronic hepatitis C infection. His renal insufficiency could be a result of hypertension, diabetes, or dehydration given that he has been bed‐bound.

Most intriguing are the normal PSA level and only slightly elevated AFP level. PSA is useful for detecting recurrence of prostate cancer or following response of therapy, but the utility of PSA as a screening tool remains controversial in part because of its low specificity. Prostate cancer is the most commonly diagnosed cancer among men and cannot be ruled out by a normal PSA. In a patient with hepatitis C, cirrhosis (which we have not conclusively diagnosed), and a radiologically suspicious liver lesion, an AFP > 200 g/L would be diagnostic of HCC. In this case, however, mildly elevated AFP does not help us to either diagnose or exclude HCC.

The chest x‐ray showed no abnormalities. MRI of the spine revealed lytic lesions in the T7‐T10 vertebral bodies with spinal cord compression at the T7 level (Fig. 1).

Figure 1

A repeat CT scan of the abdomen showed a coarse, nodular liver with 2 heterogeneous, early‐enhancing masses (4.7 4.2 and 3.4 2.4 cm in diameter) with surrounding satellite lesions (Fig. 2).

Figure 2

The enhancement pattern on dual‐phase liver protocol CT was not characteristic of HCC. The left portal vein was not visualized. Splenomegaly and esophageal varices were observed. The adrenal glands showed bilateral, heterogeneous enhancing masses. The epiphrenic, retroperitoneal, and periportal lymph nodes were enlarged. Lytic lesions were seen in the sacrum, left iliac wing, and T7‐T10 vertebral bodies.

Intravenous high‐dose steroids were started. The neurosurgery team advised that no surgical interventions were appropriate because of the patient's poor functional status and the extent of his disease.

It is unfortunate that no neurosurgical interventions could help this patient, especially because we are not yet sure of the final diagnosis. Standard indications for neurosurgical decompression include compression from bone fragments, spinal instability requiring fixation, and lack of response to radiation therapy. Patients must also be able to tolerate surgery. Although evidence supports the use of corticosteroids in reducing edema, inflammation, and neurological deficits in malignant spinal cord compression, there is not consensus on what the optimal dose is. Doses of 16‐100 mg of dexamethasone per day appear to be beneficial, as long as higher doses are rapidly tapered to avoid toxic effects. High‐dose steroids minimize the initial edema but are unlikely to change the long‐term outcome of patients who are nonambulatory on arrival.

The CT scan does not help us distinguish between metastatic cancer and primary HCC. Adrenal metastases are very uncommon in HCC. Lung cancer, however, metastasizes to the liver, adrenal glands, and spine, even without significant pulmonary symptoms. HCC may be seen on CT as a solitary mass, a dominant mass with surrounding satellite lesions, multifocal lesions, or a diffusely infiltrating tumor. This diagnosis now seems more likely given the finding of cirrhosis, which increases the risk of HCC in individuals with hepatitis C infection.

We need to obtain tissue for diagnosis and prognosis and to guide therapy. I would consult with radiology and gastroenterology colleagues about the best location to biopsy, but a bone biopsy should be avoided because the pathologic yield is lower.

The radiology and gastroenterology consultants recommended adrenal biopsy because there was easier posterior access for tissue. A liver biopsy was avoided because of the risk of bleeding with hypervascular masses. Fine‐needle aspiration of the mass in the right adrenal gland was performed. The pathology demonstrated bile production and hexagonal arrangement of cells with endothelial cuffing consistent with hepatocellular carcinoma. The oncology staff was consulted about palliative chemotherapy options. The patient began radiation therapy directed at the T7 lesion compressing the spinal cord. He regained minimal movement of his foot. After discussing treatment options with the oncology staff, the patient declined chemotherapy and was transitioned to hospice, where he died 3 weeks later.

COMMENTARY

Hepatocellular carcinoma (HCC) is the third‐leading cause of cancer death and the fifth‐leading cause of cancer worldwide. It causes nearly 1 million deaths annually, and unlike many other cancers, its incidence and mortality rate are rising. Most cases of HCC in Africa and Asia are a result of chronic hepatitis B infection, but in the United States HCC is primarily attributable to hepatitis C infection.1 The annual incidence of HCC in the U.S. population, now about 4 cases per 100,000 people,2 is rising because of the increased prevalence of hepatitis C. Other causes of HCC, such as alcoholic liver disease, hepatitis B infection, and hemochromatosis, have remained stable and have not contributed as significantly to the rising incidence of HCC. For the individual patient, hepatitis C infection conveys a 20‐fold increase in the risk for HCC (2%‐8% risk/year).1 Eighty percent of cases of HCC develop in patients with cirrhosis.3 Unlike patients with hepatitis B infection, persons chronically infected with hepatitis C rarely develop HCC unless they have cirrhosis.

The American Association for the Study of Liver Disease recommends that hepatitis Binfected individuals at high risk for HCC (eg, men older than 40 years and persons with cirrhosis or a family history of HCC) and hepatitis Cinfected individuals with cirrhosis4 be periodically screened for HCC with alpha‐fetoprotein (AFP) and ultrasonography (every 6 months to approximate the doubling time of the tumor5). Using the most commonly reported cutoff for a positive test result for hepatocellular carcinoma (AFP level > 20 g/L) resulted in the following test characteristics: sensitivity, 41%‐65%; specificity, 80%‐94%; positive likelihood ratio, 3.1‐6.8; and negative likelihood ratio, 0.4‐0.6.6 AFP alone is therefore a poor screening test for HCC, and as shown in this case, AFP levels can be normal or only minimally elevated in the setting of diffusely metastatic disease. Ultrasonography alone is only 35%‐87% sensitive in detecting HCC,79 but the combination of AFP and ultrasonography identified 100% of the HCC cases in one small case series.10

For the patient in this case, the optimal clinical pathway would have been to transition from screening to diagnostic measures in a timely manner. Consensus guidelines from the European Association for Study of the Liver in 2001 recommend biopsy of all focal liver lesions that are between 1 and 2 cm.11 The American Association for the Study of Liver Diseases (AASLD) recommends that focal liver lesions between 1 and 2 cm found on ultrasound in cirrhotic livers be followed by 2 dynamic studies: CT, MRI, or contrast ultrasound. If 2 separate studies reveal typical characteristics of HCC, then the lesion should be treated as HCC, and if not typical, then the lesion should be biopsied.4 Although no studies were available to support the recommendations, both the EASL and AASLD advise that lesions greater than 2 cm with demonstrated vascularity on both ultrasonography and CT can be diagnosed as HCC without biopsy and that lesions smaller than 1 cm be monitored.4, 11

Hepatocellular carcinoma can metastasize to almost anywhere in the body by hematologic or lymphatic spread or by direct extension. The most common site for metastases of HCC is the lung. Metastases to the lung arise primarily from arterial emboli and therefore are most common in the lower lobes, where there is greater perfusion.12 The second most common site is intraabdominal lymph nodes. The axial skeleton is the third most common site of metastases and, as in this case, primarily involves the spine.13 Other sites of metastases include the peritoneum, the inferior vena cava and right atrium by direct extension, and, less commonly, the gallbladder and spleen. Autopsy studies of patients with HCC found that 8% had metastases to the adrenal glands, as did this patient.13 Metastasis to the central nervous system is rare.

There were several challenging aspects of this case, including atypical radiologic appearance, an unusual metastatic pattern, and minimally elevated AFP level. This case raises 3 key points that we must remember as clinicians:

• 1

  Patients infected with hepatitis C who are found to have suspicious hepatic lesions should be aggressively evaluated for HCC.

• 2

  Using an AFP level < 20 g/L as a screening test is not helpful because this level can be seen even with widely metastatic disease.

• 3

  Knowledge of available screening tests as well as the many possible manifestations of HCC helps clinicians to diagnose HCC earlier, when the disease is potentially curable.

Hospitalists are on the front lines of care for patients with cerebrovascular accidents. After the first steps in acute stroke management occur in the emergency room, care is frequently transferred to the hospitalist. This review focuses on the evidence‐based management of blood pressure following acute ischemic stroke. Management of blood pressure after stroke is still controversial, and current consensus statement guidelines acknowledge that optimal treatment has not yet been established.1, 2 As such, it is essential to understand the changes in normal homeostatic physiologic processes that occur after stroke and their subsequent effects on neurologic function. Only then can the appropriate blood pressure target and antihypertensive regimen be chosen.

Physiology of Cerebral Perfusion

Once a stroke has occurred and perfusion to a section of brain tissue has been acutely compromised, systemic pressure tends to rise. This rise is presumably due in part to increased adrenergic tone and activation of the renin‐aldosterone system and potentially is part of Cushing's reflex in cases in which intracranial pressure is elevated.3 The increase in mean arterial pressure may represent a protective response. In the first major study on the topic, in 1981, on admission for stroke mean blood pressure was 163/90 mm Hg for patients without a history of hypertension and 214/118 mm Hg for patients who had been treated for hypertension previously.4 This rise in blood pressure in response to endogenous mechanisms is attenuated over the first 24 hours, and even without intervention, blood pressure tends to fall spontaneously over the next 10 days.47

Under normal circumstances, cerebral blood flow (CBF) is tightly autoregulated across a wide range of cerebral perfusion pressures by alteration in cerebrovascular resistance via arteriolar constriction.89 This allows CBF to remain constant even if cerebral perfusion pressure (CPP) fluctuates from 60 to 150 mm Hg.9 In patients with chronic hypertension, autoregulation works best with blood pressure in a higher range because of vascular smooth muscle hypertrophy and structural changes in the cerebral vessels (see Table 1).

After an acute ischemic stroke, autoregulation is lost, and local CBF becomes linearly associated with cerebral perfusion pressure. Loss of autoregulation occurs because of several local factors as a result of the infarct. Acidosis and hypoxia in the region of the stroke lead to vasodilatation in the perfusing vessels.9 This may improve local circulation in collateral vessels as a response to the obstruction in the primary supplying artery, but the consequence of maximal vasodilatation is loss of the ability to autoregulate. Normal CPP is driven by the mean arterial pressure minus the intracranial pressure. However, if intracranial vessels have lost the ability to accommodate changes in perfusion pressure, then blood flow to the area of injury becomes linearly correlated with mean arterial pressure.

Surrounding a central core of irreversible necrosis may be a zone of at‐risk tissue that is susceptible to reduction below the threshold of viability in response to any decrement in systemic mean blood pressure.11 This critical concept in stroke management is referred to as the peri‐infarct penumbra (see Fig. 1 and Table 2).

Figure 1

Blood Pressure Management after Stroke

The presence of a systemic blood pressure‐dependent peri‐infarct penumbra that might be compromised by blood pressure reduction and thus extend the infarct is the principal argument for allowing permissive hypertension. This is bolstered by the observation that decreases in blood pressure in the first 24 hours are associated with a significant risk of poor neurologic outcome.6 In their an observational study Vlcek et al. found that a greater than 25% drop in diastolic blood pressure (DBP) was associated with a 4‐fold risk of severe disability.5 In a 2003 observational study Oliveria et al. found that reduction in systolic blood pressure (SBP) in the first 24 hours was independently associated with poor outcomes, with a doubling of the risk for poor outcomes for every 10% drop in systolic blood pressure.6 In both these studies, the worsened outcome did not depend on whether the drop was spontaneous or induced by medications. Case reports suggest that large drops in blood pressure can be catastrophic and that even moderate lowering of blood pressure after acute stroke can be associated with clinical deterioration.8, 12

The primary argument for lowering blood pressure after an acute stroke hinges on secondary prevention of new ischemic events, minimization of cerebral edema, and prevention of hemorrhagic conversion. It has long been recognized that hypertension itself is a risk factor for stroke13 and that reduction in chronic hypertension is part of secondary prevention for cerebrovascular accidents.14 Further, hypertension is the most common risk factor for intracerebral hemorrhage, and it would stand to reason that damage to the brain parenchyma from ischemic stroke would increase the risk of pressure‐induced bleeding in an acute setting.15

Because there are compelling theoretical arguments both for and against lowering blood pressure after an acute stroke, it is necessary to look at the results of randomized clinical trials for guidance in weighing the risks and benefits. The overall goal of blood pressure management is to maximize perfusion to the ischemic penumbra while minimizing the hypertensive risk of hemorrhagic transformation.

Lisk et al. conducted a small randomized trial in 1993 of antihypertensive therapy versus placebo after ischemic stroke looking at SPECT perfusion and found lower CBF if mean arterial pressure (MAP) dropped more than 16%.16 This is in contrast with the results of a 1997 randomized trial of perindopril after cerebrovascular accident that found no decrease in Doppler CBF despite a 10% decrease in blood pressure in the active treatment group.17 Neither study was powered to detect significant differences in clinical outcome.

Early randomized controlled trials of antihypertensive agents after acute stroke investigated neuroprotection via mechanisms other than the antihypertensive effect. Nimodipine, a dihydropyridine derivative thought to prevent neuronal death via blockade of calcium channels, has been studied extensively.1820 A meta‐analysis of the 9 early trials of nimodipine, from 1988 to 1992, suggested that nimodipine was potentially beneficial in neurologic score and functional outcome only if used within the first 12 hours and that it could be harmful if started after 24 hours.21 Two additional studies were done in 1994 using both intravenous and oral nimodipine formulations. They demonstrated worsened neurologic function and higher mortality, respectively, which was hypothesized to be a result of the detrimental hemodynamic effects of nimodipine.18, 22

The BEST trial used beta‐blockers in the early period after acute stroke and failed to find benefit, whereas the FIST trial had similar results with the calcium channel blocker flunarizine.23, 24 The ACCESS trial in 2003 was a prospective, randomized, controlled trial using oral candesartan in the first 24 hours after stroke.25 It did find improved mortality in the candesartan arm after 1 year, yet there were no significant differences in blood pressure between candesartan and placebo. Thus, the improved outcome was presumed to be a result of mechanisms other than antihypertensive effect.

Some significant caveats should be kept in mind when interpreting the results of these studies. None of the trials was designed to titrate blood pressure to a prespecified goal in a prospective randomized fashion. It is also difficult to tease out the effect of the active medical intervention from the effect of spontaneous drops in blood pressure, and many trials did not find a significant difference in blood pressure between the medication and placebo groups. A large randomized trial to evaluate interventions to a predefined blood pressure target is needed.

The Cochrane Stroke Group reviewed 32 trials involving 5368 patients and concluded there was not enough evidence to reliably evaluate the effect of altering blood pressure on outcomes.3

Recommendations for Treatment of Hypertension in Acute Stroke

The decision of when to initiate antihypertensive therapy has not been clearly delineated. However, most experts agree that blood pressure targets need to take into account whether thrombolytics are used. The available data provide little evidence that lowering blood pressure decreases adverse events; however, there is some evidence that lowering blood pressure can worsen outcomes by expanding the area of ischemia. Thus, in treating most acute ischemic strokes, antihypertensive therapy can and should be withheld. The exception to this is stroke in a patient with comorbid hypertensive organ damage such as myocardial infarction, aortic dissection, acute hypertensive renal failure, pulmonary edema, or encephalopathy. The consensus statement of the American Stroke Association is to withhold treatment until blood pressure exceeds 220/120 mm Hg,1 roughly corresponding to a MAP of 150 mm Hg, the normal upper limit of cerebral autoregulation. Treatment optimally should be titratable in order to avoid overcorrection, preferably with minimal cerebral venodilatation effect. The parenteral agents labetolol, fenoldopam, nicardipine, and nitroprusside are most commonly used. A disadvantage of nitrates or nitroprusside is that their venodilating effect may raise intracranial pressure. Clonidine may induce central nervous system depression, which can complicate interpretation of the mental status of a patient with an acute neurologic event. Sublingual nifedipine should be avoided because of its well‐documented tendency to cause overcorrection of blood pressure.26 No large direct comparison trial has evaluated which of these antihypertensive agents is superior in clinical outcomes. For the hospitalist, choice of antihypertensive agent should be driven by a need for rapid control of blood pressure to target without overcorrection (see Table 3). Issues such as intracranial pressure, heart rate, and comorbidities may also play a role in choice of medication.

The risk of hemorrhagic conversion is greater when thrombolysis is used for the treatment of cerebrovascular accident, in the NINDS trial rising from 0.6% in patients receiving a placebo to 6.4% in patients receiving tPA.27 Given that the goal of thrombolysis is to restore perfusion through the previously blocked vessel and that the risk of hemorrhage rises after thrombolysis, the balance between maintaining CPP and decreasing the risk of bleeding shifts toward maintaining a lower blood pressure postthrombolysis. The NINDS thrombolytic trial required patients to have a blood pressure less than 185/110 mm Hg to be included.27 Once a thrombolytic had been administered, the permitted maximum blood pressure dropped to 180/105 mm Hg. Blood pressure needs to be monitored closely, initially every 15 minutes for 2 hours, then every 30 minutes for the next 6 hours, and then hourly until the end of the first 24 hours. After this, blood pressure monitoring intervals can be more spaced out depending on the need for active antihypertensive therapy.28 However, arterial punctures for invasive monitoring are not recommended if thrombolytics are administered. Review of the experience of the NINDS trial suggests that approximately one third of patients receiving thrombolytics will require pharmacologic therapy to reach the recommended blood pressure goals in the first 24 hours.28

Although guidelines for the management of blood pressure after cerebrovascular accident from major organizations such as the American Stroke Association and the European Stroke Initiative are published and widely quoted in reviews of stroke management, physician adherence to these guidelines is poor.1, 2933 A 2002 review of prescribing practices in a Canadian hospital found excessive reduction of blood pressure in 60% of patients where nitroglycerin was used, and sublingual nifedipine was still the second most commonly prescribed medication.34 A similar 2004 study by Lindenauer et al. found that only 26% of patients who had antihypertensive medication initiated in the hospital met consensus guidelines for therapy.35

Induced Hypertension

Hypotension should be avoided after acute stroke. Observational studies have demonstrated an increased mortality rate of patients who present with hypotension.42 Patients with acute ischemic stroke and loss of autoregulation may have impaired tolerance to even mild levels of hypotension.8 First‐line therapy for hypotension after stroke is volume resuscitation and optimization of cardiac function by correcting arrhythmias.1 If this should fail, vasopressor support is advisable to avoid ongoing hypotension and cerebral hypoperfusion.

The same physiologic arguments that favor permissively managing high blood pressure and avoiding hypotension raise the question of whether inducing hypertension through the use of vasopressors might improve outcomes of stroke. This hypothesis has been bolstered by animal studies and imaging data that suggest improved perfusion to the area of injury with vasopressor‐induced hypertension.3638 However, there are concerns that this strategy may increase edema and hemorrhage and create the potential for vasopressor‐induced myocardial ischemia or arrhythmias. Although the results of small trials have appeared promising, particularly for patients with large vessel stenosis, at this point induced hypertension is still considered experimental until the results of larger randomized, controlled trials provide greater support for this procedure.1, 3941

Chronic Blood Pressure Control for Secondary Prevention of Stroke

Multiple trials have demonstrated that interventions to treat chronic hypertension can reduce the rate of future strokes.14, 43, 44 The PROGRESS trial demonstrated that blood pressure reduction with combination therapy decreased stroke recurrence by 43%.43 Clearly long‐term blood pressure control is a vital component of secondary prevention of stroke. Based on the results of the PROGRESS and ACCESS trials, it is suggested that angiotensin‐converting enzyme (ACE) inhibitors or angiotensin receptor blockers, potentially with additional diuretic therapy, are beneficial in the treatment of chronic hypertension following cerebrovascular accident.25, 42 The issue of optimal medication class is not settled. Recommendations are to treat chronically elevated blood pressure to lower and maintain it at less than 140/80 mm Hg. Because there is no single threshold level of blood pressure beyond which the risk of cerebrovascular disease increases, reduction below this cut point may still offer incremental benefit.13, 45, 46 The timing of initiation of therapy to reach secondary‐prevention goals is not addressed in current guidelines, although some authors recommend waiting days to weeks after an acute stroke before starting therapy.1, 37 For a patient who remains hypertensive at discharge, it is incumbent on the hospitalist to communicate the plan for initiation of antihypertensive agents to the patient and the primary care physician in order to ensure that this critical secondary prevention measure is addressed.

Areas of Ambiguity and Need for Future Research

Within an evidence‐guided practice, there are still many areas for which the evidence to date does not answer important clinical questions about patient management. Whether a patient's prestroke baseline blood pressure should be considered in individualizing blood pressure goals is unclear, as is the question of whether to continue or hold previous chronic antihypertensive therapy. Given the many stroke subtypes, from tiny lacunar infarcts with little collateralization to massive malignant middle‐cerebral infarctions, should blood pressure management be individualized according to the likely size and duration of the peri‐infarct penumbra? Research is needed to determine whether reducing blood pressure to a specific target will improve outcome and the optimal timing of therapy to achieve secondary prevention goals. Finally, using the concept of the penumbra as the theoretical physiologic basis for current blood pressure recommendations, there exists a potential for rapidly evolving neuroimaging techniques to help define the presence, size, and duration of the penumbra to guide these decisions.

CONCLUSIONS

Management of blood pressure after acute ischemic stroke differs from that of many other hypertensive conditions because of the need to preserve perfusion of the peri‐infarct penumbra. Evidence to date suggests little benefit and potential harm from acutely lowering blood pressure after stroke, although there have not been large randomized trials examining outcomes when blood pressure is lowered to a prespecified goal. Current consensus guidelines suggest that blood pressure may be managed permissively up to 220/120 mm Hg when thrombolysis is not administered and to 180/105 mm Hg when thrombolysis is performed. Data suggest that low‐dose antihypertensive therapy such as ACE inhibitors or angiotensin receptor blockers may be safe in the acute setting if pressure is reduced by less than 10%‐15%.17, 25 However, the evidence is not sufficiently strong for this practice to be routinely recommended. At this point, it is recommended that hypotension be aggressively treated; however, induced hypertension remains a promising but unproven therapy. Evidence is strong that long‐term blood pressure control is key to secondary prevention of stroke, but the timing of its initiation remains poorly determined.

Hospitalists are on the front lines of care for patients with cerebrovascular accidents. After the first steps in acute stroke management occur in the emergency room, care is frequently transferred to the hospitalist. This review focuses on the evidence‐based management of blood pressure following acute ischemic stroke. Management of blood pressure after stroke is still controversial, and current consensus statement guidelines acknowledge that optimal treatment has not yet been established.1, 2 As such, it is essential to understand the changes in normal homeostatic physiologic processes that occur after stroke and their subsequent effects on neurologic function. Only then can the appropriate blood pressure target and antihypertensive regimen be chosen.

Physiology of Cerebral Perfusion

Once a stroke has occurred and perfusion to a section of brain tissue has been acutely compromised, systemic pressure tends to rise. This rise is presumably due in part to increased adrenergic tone and activation of the renin‐aldosterone system and potentially is part of Cushing's reflex in cases in which intracranial pressure is elevated.3 The increase in mean arterial pressure may represent a protective response. In the first major study on the topic, in 1981, on admission for stroke mean blood pressure was 163/90 mm Hg for patients without a history of hypertension and 214/118 mm Hg for patients who had been treated for hypertension previously.4 This rise in blood pressure in response to endogenous mechanisms is attenuated over the first 24 hours, and even without intervention, blood pressure tends to fall spontaneously over the next 10 days.47

Under normal circumstances, cerebral blood flow (CBF) is tightly autoregulated across a wide range of cerebral perfusion pressures by alteration in cerebrovascular resistance via arteriolar constriction.89 This allows CBF to remain constant even if cerebral perfusion pressure (CPP) fluctuates from 60 to 150 mm Hg.9 In patients with chronic hypertension, autoregulation works best with blood pressure in a higher range because of vascular smooth muscle hypertrophy and structural changes in the cerebral vessels (see Table 1).

After an acute ischemic stroke, autoregulation is lost, and local CBF becomes linearly associated with cerebral perfusion pressure. Loss of autoregulation occurs because of several local factors as a result of the infarct. Acidosis and hypoxia in the region of the stroke lead to vasodilatation in the perfusing vessels.9 This may improve local circulation in collateral vessels as a response to the obstruction in the primary supplying artery, but the consequence of maximal vasodilatation is loss of the ability to autoregulate. Normal CPP is driven by the mean arterial pressure minus the intracranial pressure. However, if intracranial vessels have lost the ability to accommodate changes in perfusion pressure, then blood flow to the area of injury becomes linearly correlated with mean arterial pressure.

Surrounding a central core of irreversible necrosis may be a zone of at‐risk tissue that is susceptible to reduction below the threshold of viability in response to any decrement in systemic mean blood pressure.11 This critical concept in stroke management is referred to as the peri‐infarct penumbra (see Fig. 1 and Table 2).

Figure 1

Blood Pressure Management after Stroke

The presence of a systemic blood pressure‐dependent peri‐infarct penumbra that might be compromised by blood pressure reduction and thus extend the infarct is the principal argument for allowing permissive hypertension. This is bolstered by the observation that decreases in blood pressure in the first 24 hours are associated with a significant risk of poor neurologic outcome.6 In their an observational study Vlcek et al. found that a greater than 25% drop in diastolic blood pressure (DBP) was associated with a 4‐fold risk of severe disability.5 In a 2003 observational study Oliveria et al. found that reduction in systolic blood pressure (SBP) in the first 24 hours was independently associated with poor outcomes, with a doubling of the risk for poor outcomes for every 10% drop in systolic blood pressure.6 In both these studies, the worsened outcome did not depend on whether the drop was spontaneous or induced by medications. Case reports suggest that large drops in blood pressure can be catastrophic and that even moderate lowering of blood pressure after acute stroke can be associated with clinical deterioration.8, 12

The primary argument for lowering blood pressure after an acute stroke hinges on secondary prevention of new ischemic events, minimization of cerebral edema, and prevention of hemorrhagic conversion. It has long been recognized that hypertension itself is a risk factor for stroke13 and that reduction in chronic hypertension is part of secondary prevention for cerebrovascular accidents.14 Further, hypertension is the most common risk factor for intracerebral hemorrhage, and it would stand to reason that damage to the brain parenchyma from ischemic stroke would increase the risk of pressure‐induced bleeding in an acute setting.15

Because there are compelling theoretical arguments both for and against lowering blood pressure after an acute stroke, it is necessary to look at the results of randomized clinical trials for guidance in weighing the risks and benefits. The overall goal of blood pressure management is to maximize perfusion to the ischemic penumbra while minimizing the hypertensive risk of hemorrhagic transformation.

Lisk et al. conducted a small randomized trial in 1993 of antihypertensive therapy versus placebo after ischemic stroke looking at SPECT perfusion and found lower CBF if mean arterial pressure (MAP) dropped more than 16%.16 This is in contrast with the results of a 1997 randomized trial of perindopril after cerebrovascular accident that found no decrease in Doppler CBF despite a 10% decrease in blood pressure in the active treatment group.17 Neither study was powered to detect significant differences in clinical outcome.

Early randomized controlled trials of antihypertensive agents after acute stroke investigated neuroprotection via mechanisms other than the antihypertensive effect. Nimodipine, a dihydropyridine derivative thought to prevent neuronal death via blockade of calcium channels, has been studied extensively.1820 A meta‐analysis of the 9 early trials of nimodipine, from 1988 to 1992, suggested that nimodipine was potentially beneficial in neurologic score and functional outcome only if used within the first 12 hours and that it could be harmful if started after 24 hours.21 Two additional studies were done in 1994 using both intravenous and oral nimodipine formulations. They demonstrated worsened neurologic function and higher mortality, respectively, which was hypothesized to be a result of the detrimental hemodynamic effects of nimodipine.18, 22

The BEST trial used beta‐blockers in the early period after acute stroke and failed to find benefit, whereas the FIST trial had similar results with the calcium channel blocker flunarizine.23, 24 The ACCESS trial in 2003 was a prospective, randomized, controlled trial using oral candesartan in the first 24 hours after stroke.25 It did find improved mortality in the candesartan arm after 1 year, yet there were no significant differences in blood pressure between candesartan and placebo. Thus, the improved outcome was presumed to be a result of mechanisms other than antihypertensive effect.

Some significant caveats should be kept in mind when interpreting the results of these studies. None of the trials was designed to titrate blood pressure to a prespecified goal in a prospective randomized fashion. It is also difficult to tease out the effect of the active medical intervention from the effect of spontaneous drops in blood pressure, and many trials did not find a significant difference in blood pressure between the medication and placebo groups. A large randomized trial to evaluate interventions to a predefined blood pressure target is needed.

The Cochrane Stroke Group reviewed 32 trials involving 5368 patients and concluded there was not enough evidence to reliably evaluate the effect of altering blood pressure on outcomes.3

Recommendations for Treatment of Hypertension in Acute Stroke

The decision of when to initiate antihypertensive therapy has not been clearly delineated. However, most experts agree that blood pressure targets need to take into account whether thrombolytics are used. The available data provide little evidence that lowering blood pressure decreases adverse events; however, there is some evidence that lowering blood pressure can worsen outcomes by expanding the area of ischemia. Thus, in treating most acute ischemic strokes, antihypertensive therapy can and should be withheld. The exception to this is stroke in a patient with comorbid hypertensive organ damage such as myocardial infarction, aortic dissection, acute hypertensive renal failure, pulmonary edema, or encephalopathy. The consensus statement of the American Stroke Association is to withhold treatment until blood pressure exceeds 220/120 mm Hg,1 roughly corresponding to a MAP of 150 mm Hg, the normal upper limit of cerebral autoregulation. Treatment optimally should be titratable in order to avoid overcorrection, preferably with minimal cerebral venodilatation effect. The parenteral agents labetolol, fenoldopam, nicardipine, and nitroprusside are most commonly used. A disadvantage of nitrates or nitroprusside is that their venodilating effect may raise intracranial pressure. Clonidine may induce central nervous system depression, which can complicate interpretation of the mental status of a patient with an acute neurologic event. Sublingual nifedipine should be avoided because of its well‐documented tendency to cause overcorrection of blood pressure.26 No large direct comparison trial has evaluated which of these antihypertensive agents is superior in clinical outcomes. For the hospitalist, choice of antihypertensive agent should be driven by a need for rapid control of blood pressure to target without overcorrection (see Table 3). Issues such as intracranial pressure, heart rate, and comorbidities may also play a role in choice of medication.

The risk of hemorrhagic conversion is greater when thrombolysis is used for the treatment of cerebrovascular accident, in the NINDS trial rising from 0.6% in patients receiving a placebo to 6.4% in patients receiving tPA.27 Given that the goal of thrombolysis is to restore perfusion through the previously blocked vessel and that the risk of hemorrhage rises after thrombolysis, the balance between maintaining CPP and decreasing the risk of bleeding shifts toward maintaining a lower blood pressure postthrombolysis. The NINDS thrombolytic trial required patients to have a blood pressure less than 185/110 mm Hg to be included.27 Once a thrombolytic had been administered, the permitted maximum blood pressure dropped to 180/105 mm Hg. Blood pressure needs to be monitored closely, initially every 15 minutes for 2 hours, then every 30 minutes for the next 6 hours, and then hourly until the end of the first 24 hours. After this, blood pressure monitoring intervals can be more spaced out depending on the need for active antihypertensive therapy.28 However, arterial punctures for invasive monitoring are not recommended if thrombolytics are administered. Review of the experience of the NINDS trial suggests that approximately one third of patients receiving thrombolytics will require pharmacologic therapy to reach the recommended blood pressure goals in the first 24 hours.28

Although guidelines for the management of blood pressure after cerebrovascular accident from major organizations such as the American Stroke Association and the European Stroke Initiative are published and widely quoted in reviews of stroke management, physician adherence to these guidelines is poor.1, 2933 A 2002 review of prescribing practices in a Canadian hospital found excessive reduction of blood pressure in 60% of patients where nitroglycerin was used, and sublingual nifedipine was still the second most commonly prescribed medication.34 A similar 2004 study by Lindenauer et al. found that only 26% of patients who had antihypertensive medication initiated in the hospital met consensus guidelines for therapy.35

Induced Hypertension

Hypotension should be avoided after acute stroke. Observational studies have demonstrated an increased mortality rate of patients who present with hypotension.42 Patients with acute ischemic stroke and loss of autoregulation may have impaired tolerance to even mild levels of hypotension.8 First‐line therapy for hypotension after stroke is volume resuscitation and optimization of cardiac function by correcting arrhythmias.1 If this should fail, vasopressor support is advisable to avoid ongoing hypotension and cerebral hypoperfusion.

The same physiologic arguments that favor permissively managing high blood pressure and avoiding hypotension raise the question of whether inducing hypertension through the use of vasopressors might improve outcomes of stroke. This hypothesis has been bolstered by animal studies and imaging data that suggest improved perfusion to the area of injury with vasopressor‐induced hypertension.3638 However, there are concerns that this strategy may increase edema and hemorrhage and create the potential for vasopressor‐induced myocardial ischemia or arrhythmias. Although the results of small trials have appeared promising, particularly for patients with large vessel stenosis, at this point induced hypertension is still considered experimental until the results of larger randomized, controlled trials provide greater support for this procedure.1, 3941

Chronic Blood Pressure Control for Secondary Prevention of Stroke

Multiple trials have demonstrated that interventions to treat chronic hypertension can reduce the rate of future strokes.14, 43, 44 The PROGRESS trial demonstrated that blood pressure reduction with combination therapy decreased stroke recurrence by 43%.43 Clearly long‐term blood pressure control is a vital component of secondary prevention of stroke. Based on the results of the PROGRESS and ACCESS trials, it is suggested that angiotensin‐converting enzyme (ACE) inhibitors or angiotensin receptor blockers, potentially with additional diuretic therapy, are beneficial in the treatment of chronic hypertension following cerebrovascular accident.25, 42 The issue of optimal medication class is not settled. Recommendations are to treat chronically elevated blood pressure to lower and maintain it at less than 140/80 mm Hg. Because there is no single threshold level of blood pressure beyond which the risk of cerebrovascular disease increases, reduction below this cut point may still offer incremental benefit.13, 45, 46 The timing of initiation of therapy to reach secondary‐prevention goals is not addressed in current guidelines, although some authors recommend waiting days to weeks after an acute stroke before starting therapy.1, 37 For a patient who remains hypertensive at discharge, it is incumbent on the hospitalist to communicate the plan for initiation of antihypertensive agents to the patient and the primary care physician in order to ensure that this critical secondary prevention measure is addressed.

Areas of Ambiguity and Need for Future Research

Within an evidence‐guided practice, there are still many areas for which the evidence to date does not answer important clinical questions about patient management. Whether a patient's prestroke baseline blood pressure should be considered in individualizing blood pressure goals is unclear, as is the question of whether to continue or hold previous chronic antihypertensive therapy. Given the many stroke subtypes, from tiny lacunar infarcts with little collateralization to massive malignant middle‐cerebral infarctions, should blood pressure management be individualized according to the likely size and duration of the peri‐infarct penumbra? Research is needed to determine whether reducing blood pressure to a specific target will improve outcome and the optimal timing of therapy to achieve secondary prevention goals. Finally, using the concept of the penumbra as the theoretical physiologic basis for current blood pressure recommendations, there exists a potential for rapidly evolving neuroimaging techniques to help define the presence, size, and duration of the penumbra to guide these decisions.

CONCLUSIONS

Management of blood pressure after acute ischemic stroke differs from that of many other hypertensive conditions because of the need to preserve perfusion of the peri‐infarct penumbra. Evidence to date suggests little benefit and potential harm from acutely lowering blood pressure after stroke, although there have not been large randomized trials examining outcomes when blood pressure is lowered to a prespecified goal. Current consensus guidelines suggest that blood pressure may be managed permissively up to 220/120 mm Hg when thrombolysis is not administered and to 180/105 mm Hg when thrombolysis is performed. Data suggest that low‐dose antihypertensive therapy such as ACE inhibitors or angiotensin receptor blockers may be safe in the acute setting if pressure is reduced by less than 10%‐15%.17, 25 However, the evidence is not sufficiently strong for this practice to be routinely recommended. At this point, it is recommended that hypotension be aggressively treated; however, induced hypertension remains a promising but unproven therapy. Evidence is strong that long‐term blood pressure control is key to secondary prevention of stroke, but the timing of its initiation remains poorly determined.

Hospitalists are on the front lines of care for patients with cerebrovascular accidents. After the first steps in acute stroke management occur in the emergency room, care is frequently transferred to the hospitalist. This review focuses on the evidence‐based management of blood pressure following acute ischemic stroke. Management of blood pressure after stroke is still controversial, and current consensus statement guidelines acknowledge that optimal treatment has not yet been established.1, 2 As such, it is essential to understand the changes in normal homeostatic physiologic processes that occur after stroke and their subsequent effects on neurologic function. Only then can the appropriate blood pressure target and antihypertensive regimen be chosen.

Physiology of Cerebral Perfusion

Once a stroke has occurred and perfusion to a section of brain tissue has been acutely compromised, systemic pressure tends to rise. This rise is presumably due in part to increased adrenergic tone and activation of the renin‐aldosterone system and potentially is part of Cushing's reflex in cases in which intracranial pressure is elevated.3 The increase in mean arterial pressure may represent a protective response. In the first major study on the topic, in 1981, on admission for stroke mean blood pressure was 163/90 mm Hg for patients without a history of hypertension and 214/118 mm Hg for patients who had been treated for hypertension previously.4 This rise in blood pressure in response to endogenous mechanisms is attenuated over the first 24 hours, and even without intervention, blood pressure tends to fall spontaneously over the next 10 days.47

Under normal circumstances, cerebral blood flow (CBF) is tightly autoregulated across a wide range of cerebral perfusion pressures by alteration in cerebrovascular resistance via arteriolar constriction.89 This allows CBF to remain constant even if cerebral perfusion pressure (CPP) fluctuates from 60 to 150 mm Hg.9 In patients with chronic hypertension, autoregulation works best with blood pressure in a higher range because of vascular smooth muscle hypertrophy and structural changes in the cerebral vessels (see Table 1).

After an acute ischemic stroke, autoregulation is lost, and local CBF becomes linearly associated with cerebral perfusion pressure. Loss of autoregulation occurs because of several local factors as a result of the infarct. Acidosis and hypoxia in the region of the stroke lead to vasodilatation in the perfusing vessels.9 This may improve local circulation in collateral vessels as a response to the obstruction in the primary supplying artery, but the consequence of maximal vasodilatation is loss of the ability to autoregulate. Normal CPP is driven by the mean arterial pressure minus the intracranial pressure. However, if intracranial vessels have lost the ability to accommodate changes in perfusion pressure, then blood flow to the area of injury becomes linearly correlated with mean arterial pressure.

Surrounding a central core of irreversible necrosis may be a zone of at‐risk tissue that is susceptible to reduction below the threshold of viability in response to any decrement in systemic mean blood pressure.11 This critical concept in stroke management is referred to as the peri‐infarct penumbra (see Fig. 1 and Table 2).

Figure 1

Blood Pressure Management after Stroke

The presence of a systemic blood pressure‐dependent peri‐infarct penumbra that might be compromised by blood pressure reduction and thus extend the infarct is the principal argument for allowing permissive hypertension. This is bolstered by the observation that decreases in blood pressure in the first 24 hours are associated with a significant risk of poor neurologic outcome.6 In their an observational study Vlcek et al. found that a greater than 25% drop in diastolic blood pressure (DBP) was associated with a 4‐fold risk of severe disability.5 In a 2003 observational study Oliveria et al. found that reduction in systolic blood pressure (SBP) in the first 24 hours was independently associated with poor outcomes, with a doubling of the risk for poor outcomes for every 10% drop in systolic blood pressure.6 In both these studies, the worsened outcome did not depend on whether the drop was spontaneous or induced by medications. Case reports suggest that large drops in blood pressure can be catastrophic and that even moderate lowering of blood pressure after acute stroke can be associated with clinical deterioration.8, 12

The primary argument for lowering blood pressure after an acute stroke hinges on secondary prevention of new ischemic events, minimization of cerebral edema, and prevention of hemorrhagic conversion. It has long been recognized that hypertension itself is a risk factor for stroke13 and that reduction in chronic hypertension is part of secondary prevention for cerebrovascular accidents.14 Further, hypertension is the most common risk factor for intracerebral hemorrhage, and it would stand to reason that damage to the brain parenchyma from ischemic stroke would increase the risk of pressure‐induced bleeding in an acute setting.15

Because there are compelling theoretical arguments both for and against lowering blood pressure after an acute stroke, it is necessary to look at the results of randomized clinical trials for guidance in weighing the risks and benefits. The overall goal of blood pressure management is to maximize perfusion to the ischemic penumbra while minimizing the hypertensive risk of hemorrhagic transformation.

Lisk et al. conducted a small randomized trial in 1993 of antihypertensive therapy versus placebo after ischemic stroke looking at SPECT perfusion and found lower CBF if mean arterial pressure (MAP) dropped more than 16%.16 This is in contrast with the results of a 1997 randomized trial of perindopril after cerebrovascular accident that found no decrease in Doppler CBF despite a 10% decrease in blood pressure in the active treatment group.17 Neither study was powered to detect significant differences in clinical outcome.

Early randomized controlled trials of antihypertensive agents after acute stroke investigated neuroprotection via mechanisms other than the antihypertensive effect. Nimodipine, a dihydropyridine derivative thought to prevent neuronal death via blockade of calcium channels, has been studied extensively.1820 A meta‐analysis of the 9 early trials of nimodipine, from 1988 to 1992, suggested that nimodipine was potentially beneficial in neurologic score and functional outcome only if used within the first 12 hours and that it could be harmful if started after 24 hours.21 Two additional studies were done in 1994 using both intravenous and oral nimodipine formulations. They demonstrated worsened neurologic function and higher mortality, respectively, which was hypothesized to be a result of the detrimental hemodynamic effects of nimodipine.18, 22

The BEST trial used beta‐blockers in the early period after acute stroke and failed to find benefit, whereas the FIST trial had similar results with the calcium channel blocker flunarizine.23, 24 The ACCESS trial in 2003 was a prospective, randomized, controlled trial using oral candesartan in the first 24 hours after stroke.25 It did find improved mortality in the candesartan arm after 1 year, yet there were no significant differences in blood pressure between candesartan and placebo. Thus, the improved outcome was presumed to be a result of mechanisms other than antihypertensive effect.

Some significant caveats should be kept in mind when interpreting the results of these studies. None of the trials was designed to titrate blood pressure to a prespecified goal in a prospective randomized fashion. It is also difficult to tease out the effect of the active medical intervention from the effect of spontaneous drops in blood pressure, and many trials did not find a significant difference in blood pressure between the medication and placebo groups. A large randomized trial to evaluate interventions to a predefined blood pressure target is needed.

The Cochrane Stroke Group reviewed 32 trials involving 5368 patients and concluded there was not enough evidence to reliably evaluate the effect of altering blood pressure on outcomes.3

Recommendations for Treatment of Hypertension in Acute Stroke

The decision of when to initiate antihypertensive therapy has not been clearly delineated. However, most experts agree that blood pressure targets need to take into account whether thrombolytics are used. The available data provide little evidence that lowering blood pressure decreases adverse events; however, there is some evidence that lowering blood pressure can worsen outcomes by expanding the area of ischemia. Thus, in treating most acute ischemic strokes, antihypertensive therapy can and should be withheld. The exception to this is stroke in a patient with comorbid hypertensive organ damage such as myocardial infarction, aortic dissection, acute hypertensive renal failure, pulmonary edema, or encephalopathy. The consensus statement of the American Stroke Association is to withhold treatment until blood pressure exceeds 220/120 mm Hg,1 roughly corresponding to a MAP of 150 mm Hg, the normal upper limit of cerebral autoregulation. Treatment optimally should be titratable in order to avoid overcorrection, preferably with minimal cerebral venodilatation effect. The parenteral agents labetolol, fenoldopam, nicardipine, and nitroprusside are most commonly used. A disadvantage of nitrates or nitroprusside is that their venodilating effect may raise intracranial pressure. Clonidine may induce central nervous system depression, which can complicate interpretation of the mental status of a patient with an acute neurologic event. Sublingual nifedipine should be avoided because of its well‐documented tendency to cause overcorrection of blood pressure.26 No large direct comparison trial has evaluated which of these antihypertensive agents is superior in clinical outcomes. For the hospitalist, choice of antihypertensive agent should be driven by a need for rapid control of blood pressure to target without overcorrection (see Table 3). Issues such as intracranial pressure, heart rate, and comorbidities may also play a role in choice of medication.

The risk of hemorrhagic conversion is greater when thrombolysis is used for the treatment of cerebrovascular accident, in the NINDS trial rising from 0.6% in patients receiving a placebo to 6.4% in patients receiving tPA.27 Given that the goal of thrombolysis is to restore perfusion through the previously blocked vessel and that the risk of hemorrhage rises after thrombolysis, the balance between maintaining CPP and decreasing the risk of bleeding shifts toward maintaining a lower blood pressure postthrombolysis. The NINDS thrombolytic trial required patients to have a blood pressure less than 185/110 mm Hg to be included.27 Once a thrombolytic had been administered, the permitted maximum blood pressure dropped to 180/105 mm Hg. Blood pressure needs to be monitored closely, initially every 15 minutes for 2 hours, then every 30 minutes for the next 6 hours, and then hourly until the end of the first 24 hours. After this, blood pressure monitoring intervals can be more spaced out depending on the need for active antihypertensive therapy.28 However, arterial punctures for invasive monitoring are not recommended if thrombolytics are administered. Review of the experience of the NINDS trial suggests that approximately one third of patients receiving thrombolytics will require pharmacologic therapy to reach the recommended blood pressure goals in the first 24 hours.28

Although guidelines for the management of blood pressure after cerebrovascular accident from major organizations such as the American Stroke Association and the European Stroke Initiative are published and widely quoted in reviews of stroke management, physician adherence to these guidelines is poor.1, 2933 A 2002 review of prescribing practices in a Canadian hospital found excessive reduction of blood pressure in 60% of patients where nitroglycerin was used, and sublingual nifedipine was still the second most commonly prescribed medication.34 A similar 2004 study by Lindenauer et al. found that only 26% of patients who had antihypertensive medication initiated in the hospital met consensus guidelines for therapy.35

Induced Hypertension

Hypotension should be avoided after acute stroke. Observational studies have demonstrated an increased mortality rate of patients who present with hypotension.42 Patients with acute ischemic stroke and loss of autoregulation may have impaired tolerance to even mild levels of hypotension.8 First‐line therapy for hypotension after stroke is volume resuscitation and optimization of cardiac function by correcting arrhythmias.1 If this should fail, vasopressor support is advisable to avoid ongoing hypotension and cerebral hypoperfusion.

The same physiologic arguments that favor permissively managing high blood pressure and avoiding hypotension raise the question of whether inducing hypertension through the use of vasopressors might improve outcomes of stroke. This hypothesis has been bolstered by animal studies and imaging data that suggest improved perfusion to the area of injury with vasopressor‐induced hypertension.3638 However, there are concerns that this strategy may increase edema and hemorrhage and create the potential for vasopressor‐induced myocardial ischemia or arrhythmias. Although the results of small trials have appeared promising, particularly for patients with large vessel stenosis, at this point induced hypertension is still considered experimental until the results of larger randomized, controlled trials provide greater support for this procedure.1, 3941

Chronic Blood Pressure Control for Secondary Prevention of Stroke

Multiple trials have demonstrated that interventions to treat chronic hypertension can reduce the rate of future strokes.14, 43, 44 The PROGRESS trial demonstrated that blood pressure reduction with combination therapy decreased stroke recurrence by 43%.43 Clearly long‐term blood pressure control is a vital component of secondary prevention of stroke. Based on the results of the PROGRESS and ACCESS trials, it is suggested that angiotensin‐converting enzyme (ACE) inhibitors or angiotensin receptor blockers, potentially with additional diuretic therapy, are beneficial in the treatment of chronic hypertension following cerebrovascular accident.25, 42 The issue of optimal medication class is not settled. Recommendations are to treat chronically elevated blood pressure to lower and maintain it at less than 140/80 mm Hg. Because there is no single threshold level of blood pressure beyond which the risk of cerebrovascular disease increases, reduction below this cut point may still offer incremental benefit.13, 45, 46 The timing of initiation of therapy to reach secondary‐prevention goals is not addressed in current guidelines, although some authors recommend waiting days to weeks after an acute stroke before starting therapy.1, 37 For a patient who remains hypertensive at discharge, it is incumbent on the hospitalist to communicate the plan for initiation of antihypertensive agents to the patient and the primary care physician in order to ensure that this critical secondary prevention measure is addressed.

Areas of Ambiguity and Need for Future Research

Within an evidence‐guided practice, there are still many areas for which the evidence to date does not answer important clinical questions about patient management. Whether a patient's prestroke baseline blood pressure should be considered in individualizing blood pressure goals is unclear, as is the question of whether to continue or hold previous chronic antihypertensive therapy. Given the many stroke subtypes, from tiny lacunar infarcts with little collateralization to massive malignant middle‐cerebral infarctions, should blood pressure management be individualized according to the likely size and duration of the peri‐infarct penumbra? Research is needed to determine whether reducing blood pressure to a specific target will improve outcome and the optimal timing of therapy to achieve secondary prevention goals. Finally, using the concept of the penumbra as the theoretical physiologic basis for current blood pressure recommendations, there exists a potential for rapidly evolving neuroimaging techniques to help define the presence, size, and duration of the penumbra to guide these decisions.

CONCLUSIONS

Management of blood pressure after acute ischemic stroke differs from that of many other hypertensive conditions because of the need to preserve perfusion of the peri‐infarct penumbra. Evidence to date suggests little benefit and potential harm from acutely lowering blood pressure after stroke, although there have not been large randomized trials examining outcomes when blood pressure is lowered to a prespecified goal. Current consensus guidelines suggest that blood pressure may be managed permissively up to 220/120 mm Hg when thrombolysis is not administered and to 180/105 mm Hg when thrombolysis is performed. Data suggest that low‐dose antihypertensive therapy such as ACE inhibitors or angiotensin receptor blockers may be safe in the acute setting if pressure is reduced by less than 10%‐15%.17, 25 However, the evidence is not sufficiently strong for this practice to be routinely recommended. At this point, it is recommended that hypotension be aggressively treated; however, induced hypertension remains a promising but unproven therapy. Evidence is strong that long‐term blood pressure control is key to secondary prevention of stroke, but the timing of its initiation remains poorly determined.

A 17‐year‐old female patient presented to the emergency department reporting having fever, sore throat, and pain with swallowing for several days. The result of her rapid strep screen was negative. She had an elevated white blood cell count, mildly elevated AST and ALT levels, and a positive result from a heterophile antibody test (BBL Monoslide). She was diagnosed with infectious mononucleosis. Given her inability to tolerate oral fluids, she was admitted to the hospital for intravenous hydration. After 3 days of receiving methylprednisolone intravenously, she had worsening throat pain, progressive neck swelling, difficulty handling her secretions, and new respiratory symptoms. During the examination, she was sitting upright in bed in moderate respiratory distress. She had kissing, exudative tonsils with palatal and uvular edema. Examination of her neck showed significantly enlarged anterior and posterior cervical lymph nodes without fluctuance. Her lung exam revealed subcostal retractions with transmitted upper airway sounds but good aeration. The edge of her liver and spleen tip were palpable.

Because of the rapid progression of symptoms while on medical therapy, computed tomography (CT) of the neck was performed. Sagittal reconstructions showed adenoidal hypertrophy compromising her nasopharynx, and massive tonsillar enlargement causing nearly complete obstruction of her oropharyngeal airway (Fig. 1), with airway narrowing to less than 2.5 mm in axial images. Bilateral low‐density lesions within the paratonsillar regions were suggestive of abscesses and retropharyngeal soft‐tissue swelling was consistent with phlegmon (Fig. 2). The patient was taken to the operating room for an emergent tonsillectomy. Bilateral peritonsillar abscesses were drained, pus was sent for culture, and her tonsils were excised. Cultures from the abscesses grew Streptococcus milleri. The patient was discharged home 2 days later to complete a 2‐week course of oral clindamycin.

Figure 1

Figure 2

Most patients with infectious mononucleosis (IM) have a benign, self‐limited course. However, a wide range of severe complications have been described including airway obstruction, splenic rupture, meningoencephalitis, Guillain‐Barr syndrome, peritonsillar abscess, and hemolytic anemia.1, 2 Upper‐airway obstruction results from lymphoid hyperplasia throughout Waldeyer's ring, with associated soft‐tissue edema. As many as 25% of patients hospitalized for IM will have some degree of airway obstruction.2, 3 Peritonsillar abscesses (PTAs) occur in approximately 1% of hospitalized patients with IM and may further obstruct the airway.4 Most commonly, peritonsillar abscesses are polymicrobial, having both aerobic and anaerobic bacteria. In a study of young adults with peritonsillar abscesses from all causes, Streptococcus pyogenes was the most common aerobe, found in nearly half of isolates; Streptococcus milleri, the bacterium isolated from our patient, was the second most common organism, found in approximately 25% of these abscesses.5 One prior case of airway obstruction from IM complicated by bilateral peritonsillar abscesses has been reported6; however, this patient was not reported to have concomitant retropharyngeal infection, as was noted in our patient.

Guidelines suggest that patients with mild, uncomplicated IM should be managed with supportive care alone; current recommendations are that steroids be prescribed only for specific complications of IM, including upper‐airway obstruction.7 Protocols for steroid regimens include initial prednisone doses ranging from 20 to 80 mg/day, with most advocating that they be tapered off over 1‐2 weeks.7, 8

Some of the controversy about the routine use of steroids in IM is related to concern for potential infectious complications associated with immunosuppression. In a small case series, Handler et al. proposed that there is an association between steroid therapy and the development of peritonsillar abscesses.9 However, this has not been tested in controlled trials, and the results of more recent studies do not support an increased likelihood of PTA in patients with infectious mononucleosis treated with corticosteroids.10, 11 Therefore, given that it has documented benefits and no proven adverse consequences, steroid therapy is uniformly recommended for patients with upper‐airway obstruction secondary to infectious mononucleosis. However, use of steroids also mandates careful monitoring for signs or symptoms suggestive of secondary bacterial infection.

For patients whose symptoms progress despite medical management including steroid therapy, surgical intervention may be required. Both tracheostomy and tonsillectomy during acute infection, sometimes referred to as hot tonsillectomy, have been reported as surgical options for airway obstruction in IM, the latter having emerged as the preferred treatment.3 Such treatment allows for drainage of any infectious collections, as well as removal of obstructing lymphoid tissue as indicated.

In conclusion, enlargement of tonsils and adenoids with associated edema in infectious mononucleosis can lead to upper‐airway obstruction. Patients with evidence of such obstruction should be treated with a tapering course of corticosteroids. Peritonsillar abscesses and deep neck infections are also severe complications of IM and can cause further respiratory compromise. In cases where medical therapy is not effective, such as with our patient, evaluation for peritonsillar abscess and need for possible acute tonsillectomy may be required.

A 17‐year‐old female patient presented to the emergency department reporting having fever, sore throat, and pain with swallowing for several days. The result of her rapid strep screen was negative. She had an elevated white blood cell count, mildly elevated AST and ALT levels, and a positive result from a heterophile antibody test (BBL Monoslide). She was diagnosed with infectious mononucleosis. Given her inability to tolerate oral fluids, she was admitted to the hospital for intravenous hydration. After 3 days of receiving methylprednisolone intravenously, she had worsening throat pain, progressive neck swelling, difficulty handling her secretions, and new respiratory symptoms. During the examination, she was sitting upright in bed in moderate respiratory distress. She had kissing, exudative tonsils with palatal and uvular edema. Examination of her neck showed significantly enlarged anterior and posterior cervical lymph nodes without fluctuance. Her lung exam revealed subcostal retractions with transmitted upper airway sounds but good aeration. The edge of her liver and spleen tip were palpable.

Because of the rapid progression of symptoms while on medical therapy, computed tomography (CT) of the neck was performed. Sagittal reconstructions showed adenoidal hypertrophy compromising her nasopharynx, and massive tonsillar enlargement causing nearly complete obstruction of her oropharyngeal airway (Fig. 1), with airway narrowing to less than 2.5 mm in axial images. Bilateral low‐density lesions within the paratonsillar regions were suggestive of abscesses and retropharyngeal soft‐tissue swelling was consistent with phlegmon (Fig. 2). The patient was taken to the operating room for an emergent tonsillectomy. Bilateral peritonsillar abscesses were drained, pus was sent for culture, and her tonsils were excised. Cultures from the abscesses grew Streptococcus milleri. The patient was discharged home 2 days later to complete a 2‐week course of oral clindamycin.

Figure 1

Figure 2

Most patients with infectious mononucleosis (IM) have a benign, self‐limited course. However, a wide range of severe complications have been described including airway obstruction, splenic rupture, meningoencephalitis, Guillain‐Barr syndrome, peritonsillar abscess, and hemolytic anemia.1, 2 Upper‐airway obstruction results from lymphoid hyperplasia throughout Waldeyer's ring, with associated soft‐tissue edema. As many as 25% of patients hospitalized for IM will have some degree of airway obstruction.2, 3 Peritonsillar abscesses (PTAs) occur in approximately 1% of hospitalized patients with IM and may further obstruct the airway.4 Most commonly, peritonsillar abscesses are polymicrobial, having both aerobic and anaerobic bacteria. In a study of young adults with peritonsillar abscesses from all causes, Streptococcus pyogenes was the most common aerobe, found in nearly half of isolates; Streptococcus milleri, the bacterium isolated from our patient, was the second most common organism, found in approximately 25% of these abscesses.5 One prior case of airway obstruction from IM complicated by bilateral peritonsillar abscesses has been reported6; however, this patient was not reported to have concomitant retropharyngeal infection, as was noted in our patient.

Guidelines suggest that patients with mild, uncomplicated IM should be managed with supportive care alone; current recommendations are that steroids be prescribed only for specific complications of IM, including upper‐airway obstruction.7 Protocols for steroid regimens include initial prednisone doses ranging from 20 to 80 mg/day, with most advocating that they be tapered off over 1‐2 weeks.7, 8

Some of the controversy about the routine use of steroids in IM is related to concern for potential infectious complications associated with immunosuppression. In a small case series, Handler et al. proposed that there is an association between steroid therapy and the development of peritonsillar abscesses.9 However, this has not been tested in controlled trials, and the results of more recent studies do not support an increased likelihood of PTA in patients with infectious mononucleosis treated with corticosteroids.10, 11 Therefore, given that it has documented benefits and no proven adverse consequences, steroid therapy is uniformly recommended for patients with upper‐airway obstruction secondary to infectious mononucleosis. However, use of steroids also mandates careful monitoring for signs or symptoms suggestive of secondary bacterial infection.

For patients whose symptoms progress despite medical management including steroid therapy, surgical intervention may be required. Both tracheostomy and tonsillectomy during acute infection, sometimes referred to as hot tonsillectomy, have been reported as surgical options for airway obstruction in IM, the latter having emerged as the preferred treatment.3 Such treatment allows for drainage of any infectious collections, as well as removal of obstructing lymphoid tissue as indicated.

In conclusion, enlargement of tonsils and adenoids with associated edema in infectious mononucleosis can lead to upper‐airway obstruction. Patients with evidence of such obstruction should be treated with a tapering course of corticosteroids. Peritonsillar abscesses and deep neck infections are also severe complications of IM and can cause further respiratory compromise. In cases where medical therapy is not effective, such as with our patient, evaluation for peritonsillar abscess and need for possible acute tonsillectomy may be required.

A 17‐year‐old female patient presented to the emergency department reporting having fever, sore throat, and pain with swallowing for several days. The result of her rapid strep screen was negative. She had an elevated white blood cell count, mildly elevated AST and ALT levels, and a positive result from a heterophile antibody test (BBL Monoslide). She was diagnosed with infectious mononucleosis. Given her inability to tolerate oral fluids, she was admitted to the hospital for intravenous hydration. After 3 days of receiving methylprednisolone intravenously, she had worsening throat pain, progressive neck swelling, difficulty handling her secretions, and new respiratory symptoms. During the examination, she was sitting upright in bed in moderate respiratory distress. She had kissing, exudative tonsils with palatal and uvular edema. Examination of her neck showed significantly enlarged anterior and posterior cervical lymph nodes without fluctuance. Her lung exam revealed subcostal retractions with transmitted upper airway sounds but good aeration. The edge of her liver and spleen tip were palpable.

Because of the rapid progression of symptoms while on medical therapy, computed tomography (CT) of the neck was performed. Sagittal reconstructions showed adenoidal hypertrophy compromising her nasopharynx, and massive tonsillar enlargement causing nearly complete obstruction of her oropharyngeal airway (Fig. 1), with airway narrowing to less than 2.5 mm in axial images. Bilateral low‐density lesions within the paratonsillar regions were suggestive of abscesses and retropharyngeal soft‐tissue swelling was consistent with phlegmon (Fig. 2). The patient was taken to the operating room for an emergent tonsillectomy. Bilateral peritonsillar abscesses were drained, pus was sent for culture, and her tonsils were excised. Cultures from the abscesses grew Streptococcus milleri. The patient was discharged home 2 days later to complete a 2‐week course of oral clindamycin.

Figure 1

Figure 2

Most patients with infectious mononucleosis (IM) have a benign, self‐limited course. However, a wide range of severe complications have been described including airway obstruction, splenic rupture, meningoencephalitis, Guillain‐Barr syndrome, peritonsillar abscess, and hemolytic anemia.1, 2 Upper‐airway obstruction results from lymphoid hyperplasia throughout Waldeyer's ring, with associated soft‐tissue edema. As many as 25% of patients hospitalized for IM will have some degree of airway obstruction.2, 3 Peritonsillar abscesses (PTAs) occur in approximately 1% of hospitalized patients with IM and may further obstruct the airway.4 Most commonly, peritonsillar abscesses are polymicrobial, having both aerobic and anaerobic bacteria. In a study of young adults with peritonsillar abscesses from all causes, Streptococcus pyogenes was the most common aerobe, found in nearly half of isolates; Streptococcus milleri, the bacterium isolated from our patient, was the second most common organism, found in approximately 25% of these abscesses.5 One prior case of airway obstruction from IM complicated by bilateral peritonsillar abscesses has been reported6; however, this patient was not reported to have concomitant retropharyngeal infection, as was noted in our patient.

Guidelines suggest that patients with mild, uncomplicated IM should be managed with supportive care alone; current recommendations are that steroids be prescribed only for specific complications of IM, including upper‐airway obstruction.7 Protocols for steroid regimens include initial prednisone doses ranging from 20 to 80 mg/day, with most advocating that they be tapered off over 1‐2 weeks.7, 8

Some of the controversy about the routine use of steroids in IM is related to concern for potential infectious complications associated with immunosuppression. In a small case series, Handler et al. proposed that there is an association between steroid therapy and the development of peritonsillar abscesses.9 However, this has not been tested in controlled trials, and the results of more recent studies do not support an increased likelihood of PTA in patients with infectious mononucleosis treated with corticosteroids.10, 11 Therefore, given that it has documented benefits and no proven adverse consequences, steroid therapy is uniformly recommended for patients with upper‐airway obstruction secondary to infectious mononucleosis. However, use of steroids also mandates careful monitoring for signs or symptoms suggestive of secondary bacterial infection.

For patients whose symptoms progress despite medical management including steroid therapy, surgical intervention may be required. Both tracheostomy and tonsillectomy during acute infection, sometimes referred to as hot tonsillectomy, have been reported as surgical options for airway obstruction in IM, the latter having emerged as the preferred treatment.3 Such treatment allows for drainage of any infectious collections, as well as removal of obstructing lymphoid tissue as indicated.

In conclusion, enlargement of tonsils and adenoids with associated edema in infectious mononucleosis can lead to upper‐airway obstruction. Patients with evidence of such obstruction should be treated with a tapering course of corticosteroids. Peritonsillar abscesses and deep neck infections are also severe complications of IM and can cause further respiratory compromise. In cases where medical therapy is not effective, such as with our patient, evaluation for peritonsillar abscess and need for possible acute tonsillectomy may be required.

Glycemic control in hospitalized patients is receiving greater attention. The American Diabetes Association and the American College of Endocrinology recently issued a joint consensus statement on the need to implement tight blood glucose (BG) control in hospitalized patients.1, 2 The Joint Commission on Accreditation of Healthcare Organizations (JACHO) has developed an Advanced Inpatient Diabetes Care Certification Program for hospitals. However, despite all these efforts, it has been difficult to change how well glucose is controlled.3 A major hurdle in implementing glycemic control strategies is the prevalent fear of hypoglycemia among hospital staff. Although there are multiple protocols for insulin treatment,47 guidelines for the prevention and treatment of hypoglycemia are lacking. Once a hypoglycemic episode has occurred, reducing the dosage of diabetes medications may reduce subsequent episodes. This study was conducted to assess whether diabetes medications were decreased following an episode of hypoglycemia that led to treatment with intravenous (IV) dextrose.

METHODS

Data were collected by the Diabetes Subcommittee of the Pharmacy and Therapeutics Committee as part of a quality improvement initiative. Hypoglycemic episodes were identified by computerized orders for 50% dextrose solution. All orders in a 1‐month period (June 2006) were collected. Characteristics of patients experiencing these episodes were identified from the electronic medical records (EMR). The following data were collected: age, sex, history of diabetes, serum creatinine, diabetes medications at time of hypoglycemia, blood glucose at time of hypoglycemia, and all BG values in the 24 hours before hypoglycemia. BG values included those obtained in the laboratory as well as those obtained by bedside blood glucose testing. Treatment changes made right when the hypoglycemic episode occurred (immediate) and within 24 hours of the hypoglycemic episode (subsequent) were evaluated by 2 diabetes specialists, a board‐certified endocrinologist and a nurse‐practitioner working on the diabetes management service. The 2 practitioners regularly work together, but the data were evaluated independently. Because there are no specific guidelines, the appropriateness of change in treatment was based on general guidelines and experience. For example, if hypoglycemia developed while a patient was on insulin infusion therapy, it was appropriate to stop the drip when the episode of hypoglycemia occurred and to restart it at a lower rate according to the insulin infusion protocol. No subsequent changes would have been made in a situation such as this, and it was deemed appropriate. However, if a patient developed hypoglycemia while on subcutaneous (SC) insulin and then insulin was either completely discontinued or no change was made in subsequent orders, it was deemed inappropriate. The 2 diabetes specialists agreed in 87% of cases (kappa = 0.68, 95% CI 0.53‐0.84). In the 13% of cases in which the diabetes specialists had different opinions, they conferred to reach agreement. In patients with more than 1 episode, data related to the first episode were evaluated. Data are presented as means with SDs.

RESULTS

The EMR contained information on time of episode of hypoglycemia and medication changes for 52 patients, all of whom were in the study. Patient characteristics and mean blood glucose level are shown in Table 1. All patients were being treated with insulin when the episode of hypoglycemia occurred: 9 were on intravenous (IV) insulin alone, 3 on IV and subcutaneous (SC) insulin, 30 on scheduled SC insulin, and 10 on sliding‐scale SC insulin alone. Three patients were prescribed sulfonylurea drugs in addition to insulin. Insulin dosage of all 52 patients was held at the time of the hypoglycemic episode. Diabetes specialists agreed with this decision 100% of the time. Only 21 patients (40%) subsequently had reductions made in their treatment dosage, and diabetes specialists agreed with the changes made for 11 of these patients (52%). Thirty‐one patients (60%) had no changes made to their treatment, and diabetes specialists agreed with that decision for 10 of these patients (32%). When diabetes specialists disagreed with a decision, they would have decreased the insulin dose or changed the regimen in a different way. Details on the changes in treatment and whether diabetes specialists agreed with the changes are shown in Table 2. Twenty‐four hours after an episode of hypoglycemia, mean blood glucose of patients whose providers had made changes was 190.7 87.9 mg/dL and that of patients whose providers had not made changes was 122.6 43.2 mg/dL (P = NS). The mean BG of patients for whom the diabetologists agreed with the decision was 110.7 90.3 mg/dL, and that of patients for whom they disagreed with the decision was 139.7 42.8 mg/dL (P = NS).

DISCUSSION

These results suggest that treatment modification following an episode of hypoglycemia may be suboptimal. These data provide no information about the clinical circumstances leading to the choice of treatment with IV dextrose, as opposed to oral glucose or glucagon. Presumably, dextrose was chosen for many patients whom the physician considered to require the most urgent treatment. Appropriately, immediate treatment with insulin was held for all patients. On the other hand, 60% of the patients continued to receive the same insulin dose 24 hours after the hypoglycemic episode. Diabetes specialists judged continuation of the same dose as inappropriate in two thirds of the cases. Even when changes in treatment were made, those changes were judged suboptimal in half the cases. Blood glucose level 24 hours after an episode of hypoglycemia reflects these problems. These findings suggest that opportunities to prevent hypoglycemic episodes in the future are frequently missed. Lack of knowledge and/or guidelines for adjusting insulin dose following an episode of hypoglycemia seemed to have led to suboptimal changes for most patients.

Overall incidence of hypoglycemia (<60 mg/dL) among patients with diabetes admitted to a hospital has been reported to be 23%.8 In patients receiving continuous intravenous insulin infusion, the incidence of hypoglycemia has been variously reported as from 1.2% to 18.7%.9, 10 All insulin infusion protocols have guidelines for the immediate treatment of hypoglycemia and recommend steps to prevent further episodes. Although many hospitals have protocols for immediate action when hypoglycemia occurs (eg, hold insulin, give juice or dextrose), to our knowledge, no specific guidelines exist for adjustment of subcutaneous insulin following an episode of hypoglycemia. The vast majority of patients in a hospital are treated with SC insulin as opposed to IV insulin, and fear of hypoglycemia is a major barrier to intensified therapy. If widely applied, standardized protocols have the potential to be effective in preventing hypoglycemia.9

A limitation of our study was that it was a retrospective data analysis. We did not look at changes in clinical condition, in nutrition, and in other medications that might have led to the episode of hypoglycemia and affected the decision about which antidiabetic medications to treat with. Data on further episodes of hypoglycemia were also not available.

In conclusion, we have shown that treatment changes after an episode of hypoglycemia are chaotic and may be suboptimal. Standardized protocols may be helpful for making effective changes and potentially can reduce the risk of further episodes of hypoglycemia.

Glycemic control in hospitalized patients is receiving greater attention. The American Diabetes Association and the American College of Endocrinology recently issued a joint consensus statement on the need to implement tight blood glucose (BG) control in hospitalized patients.1, 2 The Joint Commission on Accreditation of Healthcare Organizations (JACHO) has developed an Advanced Inpatient Diabetes Care Certification Program for hospitals. However, despite all these efforts, it has been difficult to change how well glucose is controlled.3 A major hurdle in implementing glycemic control strategies is the prevalent fear of hypoglycemia among hospital staff. Although there are multiple protocols for insulin treatment,47 guidelines for the prevention and treatment of hypoglycemia are lacking. Once a hypoglycemic episode has occurred, reducing the dosage of diabetes medications may reduce subsequent episodes. This study was conducted to assess whether diabetes medications were decreased following an episode of hypoglycemia that led to treatment with intravenous (IV) dextrose.

METHODS

Data were collected by the Diabetes Subcommittee of the Pharmacy and Therapeutics Committee as part of a quality improvement initiative. Hypoglycemic episodes were identified by computerized orders for 50% dextrose solution. All orders in a 1‐month period (June 2006) were collected. Characteristics of patients experiencing these episodes were identified from the electronic medical records (EMR). The following data were collected: age, sex, history of diabetes, serum creatinine, diabetes medications at time of hypoglycemia, blood glucose at time of hypoglycemia, and all BG values in the 24 hours before hypoglycemia. BG values included those obtained in the laboratory as well as those obtained by bedside blood glucose testing. Treatment changes made right when the hypoglycemic episode occurred (immediate) and within 24 hours of the hypoglycemic episode (subsequent) were evaluated by 2 diabetes specialists, a board‐certified endocrinologist and a nurse‐practitioner working on the diabetes management service. The 2 practitioners regularly work together, but the data were evaluated independently. Because there are no specific guidelines, the appropriateness of change in treatment was based on general guidelines and experience. For example, if hypoglycemia developed while a patient was on insulin infusion therapy, it was appropriate to stop the drip when the episode of hypoglycemia occurred and to restart it at a lower rate according to the insulin infusion protocol. No subsequent changes would have been made in a situation such as this, and it was deemed appropriate. However, if a patient developed hypoglycemia while on subcutaneous (SC) insulin and then insulin was either completely discontinued or no change was made in subsequent orders, it was deemed inappropriate. The 2 diabetes specialists agreed in 87% of cases (kappa = 0.68, 95% CI 0.53‐0.84). In the 13% of cases in which the diabetes specialists had different opinions, they conferred to reach agreement. In patients with more than 1 episode, data related to the first episode were evaluated. Data are presented as means with SDs.

RESULTS

The EMR contained information on time of episode of hypoglycemia and medication changes for 52 patients, all of whom were in the study. Patient characteristics and mean blood glucose level are shown in Table 1. All patients were being treated with insulin when the episode of hypoglycemia occurred: 9 were on intravenous (IV) insulin alone, 3 on IV and subcutaneous (SC) insulin, 30 on scheduled SC insulin, and 10 on sliding‐scale SC insulin alone. Three patients were prescribed sulfonylurea drugs in addition to insulin. Insulin dosage of all 52 patients was held at the time of the hypoglycemic episode. Diabetes specialists agreed with this decision 100% of the time. Only 21 patients (40%) subsequently had reductions made in their treatment dosage, and diabetes specialists agreed with the changes made for 11 of these patients (52%). Thirty‐one patients (60%) had no changes made to their treatment, and diabetes specialists agreed with that decision for 10 of these patients (32%). When diabetes specialists disagreed with a decision, they would have decreased the insulin dose or changed the regimen in a different way. Details on the changes in treatment and whether diabetes specialists agreed with the changes are shown in Table 2. Twenty‐four hours after an episode of hypoglycemia, mean blood glucose of patients whose providers had made changes was 190.7 87.9 mg/dL and that of patients whose providers had not made changes was 122.6 43.2 mg/dL (P = NS). The mean BG of patients for whom the diabetologists agreed with the decision was 110.7 90.3 mg/dL, and that of patients for whom they disagreed with the decision was 139.7 42.8 mg/dL (P = NS).

DISCUSSION

These results suggest that treatment modification following an episode of hypoglycemia may be suboptimal. These data provide no information about the clinical circumstances leading to the choice of treatment with IV dextrose, as opposed to oral glucose or glucagon. Presumably, dextrose was chosen for many patients whom the physician considered to require the most urgent treatment. Appropriately, immediate treatment with insulin was held for all patients. On the other hand, 60% of the patients continued to receive the same insulin dose 24 hours after the hypoglycemic episode. Diabetes specialists judged continuation of the same dose as inappropriate in two thirds of the cases. Even when changes in treatment were made, those changes were judged suboptimal in half the cases. Blood glucose level 24 hours after an episode of hypoglycemia reflects these problems. These findings suggest that opportunities to prevent hypoglycemic episodes in the future are frequently missed. Lack of knowledge and/or guidelines for adjusting insulin dose following an episode of hypoglycemia seemed to have led to suboptimal changes for most patients.

Overall incidence of hypoglycemia (<60 mg/dL) among patients with diabetes admitted to a hospital has been reported to be 23%.8 In patients receiving continuous intravenous insulin infusion, the incidence of hypoglycemia has been variously reported as from 1.2% to 18.7%.9, 10 All insulin infusion protocols have guidelines for the immediate treatment of hypoglycemia and recommend steps to prevent further episodes. Although many hospitals have protocols for immediate action when hypoglycemia occurs (eg, hold insulin, give juice or dextrose), to our knowledge, no specific guidelines exist for adjustment of subcutaneous insulin following an episode of hypoglycemia. The vast majority of patients in a hospital are treated with SC insulin as opposed to IV insulin, and fear of hypoglycemia is a major barrier to intensified therapy. If widely applied, standardized protocols have the potential to be effective in preventing hypoglycemia.9

A limitation of our study was that it was a retrospective data analysis. We did not look at changes in clinical condition, in nutrition, and in other medications that might have led to the episode of hypoglycemia and affected the decision about which antidiabetic medications to treat with. Data on further episodes of hypoglycemia were also not available.

In conclusion, we have shown that treatment changes after an episode of hypoglycemia are chaotic and may be suboptimal. Standardized protocols may be helpful for making effective changes and potentially can reduce the risk of further episodes of hypoglycemia.

Glycemic control in hospitalized patients is receiving greater attention. The American Diabetes Association and the American College of Endocrinology recently issued a joint consensus statement on the need to implement tight blood glucose (BG) control in hospitalized patients.1, 2 The Joint Commission on Accreditation of Healthcare Organizations (JACHO) has developed an Advanced Inpatient Diabetes Care Certification Program for hospitals. However, despite all these efforts, it has been difficult to change how well glucose is controlled.3 A major hurdle in implementing glycemic control strategies is the prevalent fear of hypoglycemia among hospital staff. Although there are multiple protocols for insulin treatment,47 guidelines for the prevention and treatment of hypoglycemia are lacking. Once a hypoglycemic episode has occurred, reducing the dosage of diabetes medications may reduce subsequent episodes. This study was conducted to assess whether diabetes medications were decreased following an episode of hypoglycemia that led to treatment with intravenous (IV) dextrose.

METHODS

Data were collected by the Diabetes Subcommittee of the Pharmacy and Therapeutics Committee as part of a quality improvement initiative. Hypoglycemic episodes were identified by computerized orders for 50% dextrose solution. All orders in a 1‐month period (June 2006) were collected. Characteristics of patients experiencing these episodes were identified from the electronic medical records (EMR). The following data were collected: age, sex, history of diabetes, serum creatinine, diabetes medications at time of hypoglycemia, blood glucose at time of hypoglycemia, and all BG values in the 24 hours before hypoglycemia. BG values included those obtained in the laboratory as well as those obtained by bedside blood glucose testing. Treatment changes made right when the hypoglycemic episode occurred (immediate) and within 24 hours of the hypoglycemic episode (subsequent) were evaluated by 2 diabetes specialists, a board‐certified endocrinologist and a nurse‐practitioner working on the diabetes management service. The 2 practitioners regularly work together, but the data were evaluated independently. Because there are no specific guidelines, the appropriateness of change in treatment was based on general guidelines and experience. For example, if hypoglycemia developed while a patient was on insulin infusion therapy, it was appropriate to stop the drip when the episode of hypoglycemia occurred and to restart it at a lower rate according to the insulin infusion protocol. No subsequent changes would have been made in a situation such as this, and it was deemed appropriate. However, if a patient developed hypoglycemia while on subcutaneous (SC) insulin and then insulin was either completely discontinued or no change was made in subsequent orders, it was deemed inappropriate. The 2 diabetes specialists agreed in 87% of cases (kappa = 0.68, 95% CI 0.53‐0.84). In the 13% of cases in which the diabetes specialists had different opinions, they conferred to reach agreement. In patients with more than 1 episode, data related to the first episode were evaluated. Data are presented as means with SDs.

RESULTS

The EMR contained information on time of episode of hypoglycemia and medication changes for 52 patients, all of whom were in the study. Patient characteristics and mean blood glucose level are shown in Table 1. All patients were being treated with insulin when the episode of hypoglycemia occurred: 9 were on intravenous (IV) insulin alone, 3 on IV and subcutaneous (SC) insulin, 30 on scheduled SC insulin, and 10 on sliding‐scale SC insulin alone. Three patients were prescribed sulfonylurea drugs in addition to insulin. Insulin dosage of all 52 patients was held at the time of the hypoglycemic episode. Diabetes specialists agreed with this decision 100% of the time. Only 21 patients (40%) subsequently had reductions made in their treatment dosage, and diabetes specialists agreed with the changes made for 11 of these patients (52%). Thirty‐one patients (60%) had no changes made to their treatment, and diabetes specialists agreed with that decision for 10 of these patients (32%). When diabetes specialists disagreed with a decision, they would have decreased the insulin dose or changed the regimen in a different way. Details on the changes in treatment and whether diabetes specialists agreed with the changes are shown in Table 2. Twenty‐four hours after an episode of hypoglycemia, mean blood glucose of patients whose providers had made changes was 190.7 87.9 mg/dL and that of patients whose providers had not made changes was 122.6 43.2 mg/dL (P = NS). The mean BG of patients for whom the diabetologists agreed with the decision was 110.7 90.3 mg/dL, and that of patients for whom they disagreed with the decision was 139.7 42.8 mg/dL (P = NS).

DISCUSSION

These results suggest that treatment modification following an episode of hypoglycemia may be suboptimal. These data provide no information about the clinical circumstances leading to the choice of treatment with IV dextrose, as opposed to oral glucose or glucagon. Presumably, dextrose was chosen for many patients whom the physician considered to require the most urgent treatment. Appropriately, immediate treatment with insulin was held for all patients. On the other hand, 60% of the patients continued to receive the same insulin dose 24 hours after the hypoglycemic episode. Diabetes specialists judged continuation of the same dose as inappropriate in two thirds of the cases. Even when changes in treatment were made, those changes were judged suboptimal in half the cases. Blood glucose level 24 hours after an episode of hypoglycemia reflects these problems. These findings suggest that opportunities to prevent hypoglycemic episodes in the future are frequently missed. Lack of knowledge and/or guidelines for adjusting insulin dose following an episode of hypoglycemia seemed to have led to suboptimal changes for most patients.

Overall incidence of hypoglycemia (<60 mg/dL) among patients with diabetes admitted to a hospital has been reported to be 23%.8 In patients receiving continuous intravenous insulin infusion, the incidence of hypoglycemia has been variously reported as from 1.2% to 18.7%.9, 10 All insulin infusion protocols have guidelines for the immediate treatment of hypoglycemia and recommend steps to prevent further episodes. Although many hospitals have protocols for immediate action when hypoglycemia occurs (eg, hold insulin, give juice or dextrose), to our knowledge, no specific guidelines exist for adjustment of subcutaneous insulin following an episode of hypoglycemia. The vast majority of patients in a hospital are treated with SC insulin as opposed to IV insulin, and fear of hypoglycemia is a major barrier to intensified therapy. If widely applied, standardized protocols have the potential to be effective in preventing hypoglycemia.9

A limitation of our study was that it was a retrospective data analysis. We did not look at changes in clinical condition, in nutrition, and in other medications that might have led to the episode of hypoglycemia and affected the decision about which antidiabetic medications to treat with. Data on further episodes of hypoglycemia were also not available.

In conclusion, we have shown that treatment changes after an episode of hypoglycemia are chaotic and may be suboptimal. Standardized protocols may be helpful for making effective changes and potentially can reduce the risk of further episodes of hypoglycemia.

Approximately 10 million patients present to emergency departments each year with symptoms raising concern of thromboembolism (VTE).1 The current gold standard for diagnosis of VTE is pulmonary angiography.2 As this study is invasive, alternative imaging protocols have been sought. CTPA, when combined with measures of pretest probability, equals or surpasses the ability of pulmonary angiography to detect VTE and can improve the ability of clinicians to rule out VTE.38 In a study of 930 patients, application of clinical rules in addition to _D‐dimer testing decreased the number of CTPAs ordered by 50%.9 One of the most common clinical rule sets is the Wells Score, which relies on historical features related to the risk of DVT/VTE and physical examination findings.10, 11

Other institutions have demonstrated an increase in the number of CTPAs ordered and VTE diagnoses since the study became widely available.13 Based on the observation of an increasing number of CTPAs ordered at our institution without an increase in the number of VTEs diagnosed, we aimed to ascertain the physician ordering practices for CTPA. We hypothesized that CTPAs were ordered at a greater frequency in a low‐risk population because an institutional clinical algorithm was lacking.

METHODS

Charts of all patients aged 18‐100 with CTPA ordered to rule out acute VTE were retrospectively examined. A Simplified Wells Score was applied using only the information available to the ordering physician at the time the CTPA was performed. Patients were stratified by their Simplified Wells Score to low (0‐1 points), intermediate (2‐6 points), or high (>6 points) pretest clinical probability. A _D‐dimer value, if ordered, was used to further stratify patients based on a positive or negative result. The official radiologic report of the CTPA was used to determine the rate of VTE diagnosis for the study population.

RESULTS

Three hundred and ninety‐four patients were referred for CTPA (Fig. 1). Two hundred and seventy‐nine had adequate clinical data to calculate a Simplified Wells Score and were included in the study. Of the 279 studies included, 75% were ordered through the emergency department and 25% from inpatient services (Table 1). The study patients were stratified according to the Simplified Wells criteria: 184 patients (66%) had low clinical probability, 91 (33%) had intermediate clinical probability, and 4 (1%) had high clinical probability. Nineteen (7%) patients had a history of DVT or VTE, and 28 (10%) had a history of active cancer at the time of their CTPA. One hundred and twenty‐five of the 279 patients had a _D‐dimer performed (Fig. 2). One hundred and eight were positive, and 17 were negative. Of the 17 patients who had a negative _D‐dimer and underwent CTPA testing, none were diagnosed with VTE. Eighty‐three low‐clinical‐probability patients underwent CTPA without _D‐dimer testing, 4 of whom were diagnosed with VTE.

Figure 1

Figure 2

There were 20 positive CTPAs in the study group (Fig. 3). Review of the records for 3 months after the study of patients whose CTPA was negative disclosed no diagnoses of VTE by other modalities. VTE was diagnosed in 4% of patients in the low‐clinical‐probability group, 12% in the intermediate‐clinical‐probability group, and 25% in the high‐clinical‐probability group. The overall positive CTPA rate was 7.2%.

Figure 3

DISCUSSION

Many studies have examined the application of clinical rule sets in addition to D‐dimer testing and CTPA to exclude acute VTE.39 Most of these studies have shown that the use of an algorithm is safe and frequently reduces referral for CTPA in low‐clinical‐probability patients. However, others have noted that some physicians do not routinely use validated algorithms when making decisions related to patient evaluation.13 Our rate of positive CTPA was low compared with rates reported in the literature.3, 14 We believe the most likely explanation is the large number of low‐clinical‐probability patients who underwent CTPA, possibly because providers do not routinely use a validated clinical algorithm.

When our patient population was risk stratified by Simplified Wells criteria and compared with similar data from published studies, we had a much higher proportion of patients classified as low clinical probability.7, 8, 15 The low‐clinical‐probability group's mean Simplified Wells Score was 0.71; one‐third had a Simplified Wells Score of 0. This reflects a low‐risk population for VTE, supported by the low prevalence of prior DVT/VTE and active cancer in our population.4, 10 The rationale for referring patients with so few risk factors for CTPA is unclear. It is possible that providers used CTPA to evaluate symptoms not clearly explained and obtained the study to look for other diagnoses in addition to VTE. By not applying a clinical algorithm, very‐low‐risk patients underwent CTPA, increasing the number of negative studies and decreasing the overall positive rate.

Not using a clinical algorithm also resulted in indiscriminate _D‐dimer testing. There were 83 patients risk‐stratified as low clinical probability who did not have a _D‐dimer prior to undergoing CTPA. Some of these patients may well have had a negative _D‐dimer, requiring no further workup to rule out VTE. Seventeen patients had a negative _D‐dimer and still underwent CTPA; all these patients were negative for VTE. These aberrations likely occurred from unfamiliarity with use of the _D‐dimer test or doubts about its ability to reliably exclude VTE. Appropriate application of _D‐dimer testing could have decreased the number of CTPAs ordered and increased our overall rate of positive VTE diagnosis.

Perrier et al., Brown et al., and Kelly and Wells all describe different methods of introducing clinical algorithms to aid the diagnosis of VTE.46, 9 All agree that patients should be risk stratified by pretest clinical probability, and low‐probability patients should undergo intermediate testing with _D‐dimer prior to CTPA. Implementation of a similar clinical algorithm at our facility would likely decrease the number of CTPAs ordered. If all patients presenting at our facility with signs and symptoms raising concern for VTE were first risk‐stratified by pretest clinical probability, and all low‐probability patients underwent highly‐sensitive _D‐dimer testing as an initial step, fewer CTPAs would be performed on low‐probability patients. The largest group of patients in our study were low probability; therefore, decreasing CTPA in this group could have a significant effect on our institution.

The retrospective nature of our study resulted in the following limitations. It is impossible to determine how the ordering provider viewed the patient's pretest probability. In most of the medical records, a pretest clinical probability was not documented. We attempted to validate the ordering provider's decision by being as generous as possible in applying points to the Wells Score. For example, if a patient had a remote history of cancer and the ordering provider documented this as a risk factor for VTE, the point value for cancer was given even though the Wells Score has a much narrower definition of this category.10 This practice favors assigning patients a potentially higher clinical probability and may have increased the number of patients designated as intermediate and high clinical probability in our study.

Our hospital primarily relies on CTPA with lower extremity venogram as the diagnostic test for VTE. Indeterminate tests may have occurred and thus falsely lowered the number of VTEs diagnosed. However, no patient with a negative CTPA was diagnosed with VTE by any modality in the 3 months after their initial study at our institution; a diagnosis of VTE could have been made at another hospital. The Simplified Wells Score uses both objective and subjective components to arrive at a point total. Our results might be different if newer algorithms, such as the Revised Geneva Score,16 which relies only on objective measurements, had been used.

CONCLUSIONS

The reliance on CTPA alone to exclude a potentially life‐threatening illness without additional risk stratification or clinical information leads to overuse of this test in patients with very low to no clinical risk for VTE and a low rate of diagnosed VTE. Implementation of a clinical algorithm for the diagnosis of suspected VTE may eliminate the need for many CTPAs, improving the yield of this test without compromising patient safety, especially at institutions with a low prevalence of PE.

Approximately 10 million patients present to emergency departments each year with symptoms raising concern of thromboembolism (VTE).1 The current gold standard for diagnosis of VTE is pulmonary angiography.2 As this study is invasive, alternative imaging protocols have been sought. CTPA, when combined with measures of pretest probability, equals or surpasses the ability of pulmonary angiography to detect VTE and can improve the ability of clinicians to rule out VTE.38 In a study of 930 patients, application of clinical rules in addition to _D‐dimer testing decreased the number of CTPAs ordered by 50%.9 One of the most common clinical rule sets is the Wells Score, which relies on historical features related to the risk of DVT/VTE and physical examination findings.10, 11

Other institutions have demonstrated an increase in the number of CTPAs ordered and VTE diagnoses since the study became widely available.13 Based on the observation of an increasing number of CTPAs ordered at our institution without an increase in the number of VTEs diagnosed, we aimed to ascertain the physician ordering practices for CTPA. We hypothesized that CTPAs were ordered at a greater frequency in a low‐risk population because an institutional clinical algorithm was lacking.

METHODS

Charts of all patients aged 18‐100 with CTPA ordered to rule out acute VTE were retrospectively examined. A Simplified Wells Score was applied using only the information available to the ordering physician at the time the CTPA was performed. Patients were stratified by their Simplified Wells Score to low (0‐1 points), intermediate (2‐6 points), or high (>6 points) pretest clinical probability. A _D‐dimer value, if ordered, was used to further stratify patients based on a positive or negative result. The official radiologic report of the CTPA was used to determine the rate of VTE diagnosis for the study population.

RESULTS

Three hundred and ninety‐four patients were referred for CTPA (Fig. 1). Two hundred and seventy‐nine had adequate clinical data to calculate a Simplified Wells Score and were included in the study. Of the 279 studies included, 75% were ordered through the emergency department and 25% from inpatient services (Table 1). The study patients were stratified according to the Simplified Wells criteria: 184 patients (66%) had low clinical probability, 91 (33%) had intermediate clinical probability, and 4 (1%) had high clinical probability. Nineteen (7%) patients had a history of DVT or VTE, and 28 (10%) had a history of active cancer at the time of their CTPA. One hundred and twenty‐five of the 279 patients had a _D‐dimer performed (Fig. 2). One hundred and eight were positive, and 17 were negative. Of the 17 patients who had a negative _D‐dimer and underwent CTPA testing, none were diagnosed with VTE. Eighty‐three low‐clinical‐probability patients underwent CTPA without _D‐dimer testing, 4 of whom were diagnosed with VTE.

Figure 1

Figure 2

There were 20 positive CTPAs in the study group (Fig. 3). Review of the records for 3 months after the study of patients whose CTPA was negative disclosed no diagnoses of VTE by other modalities. VTE was diagnosed in 4% of patients in the low‐clinical‐probability group, 12% in the intermediate‐clinical‐probability group, and 25% in the high‐clinical‐probability group. The overall positive CTPA rate was 7.2%.

Figure 3

DISCUSSION

Many studies have examined the application of clinical rule sets in addition to D‐dimer testing and CTPA to exclude acute VTE.39 Most of these studies have shown that the use of an algorithm is safe and frequently reduces referral for CTPA in low‐clinical‐probability patients. However, others have noted that some physicians do not routinely use validated algorithms when making decisions related to patient evaluation.13 Our rate of positive CTPA was low compared with rates reported in the literature.3, 14 We believe the most likely explanation is the large number of low‐clinical‐probability patients who underwent CTPA, possibly because providers do not routinely use a validated clinical algorithm.

When our patient population was risk stratified by Simplified Wells criteria and compared with similar data from published studies, we had a much higher proportion of patients classified as low clinical probability.7, 8, 15 The low‐clinical‐probability group's mean Simplified Wells Score was 0.71; one‐third had a Simplified Wells Score of 0. This reflects a low‐risk population for VTE, supported by the low prevalence of prior DVT/VTE and active cancer in our population.4, 10 The rationale for referring patients with so few risk factors for CTPA is unclear. It is possible that providers used CTPA to evaluate symptoms not clearly explained and obtained the study to look for other diagnoses in addition to VTE. By not applying a clinical algorithm, very‐low‐risk patients underwent CTPA, increasing the number of negative studies and decreasing the overall positive rate.

Not using a clinical algorithm also resulted in indiscriminate _D‐dimer testing. There were 83 patients risk‐stratified as low clinical probability who did not have a _D‐dimer prior to undergoing CTPA. Some of these patients may well have had a negative _D‐dimer, requiring no further workup to rule out VTE. Seventeen patients had a negative _D‐dimer and still underwent CTPA; all these patients were negative for VTE. These aberrations likely occurred from unfamiliarity with use of the _D‐dimer test or doubts about its ability to reliably exclude VTE. Appropriate application of _D‐dimer testing could have decreased the number of CTPAs ordered and increased our overall rate of positive VTE diagnosis.

Perrier et al., Brown et al., and Kelly and Wells all describe different methods of introducing clinical algorithms to aid the diagnosis of VTE.46, 9 All agree that patients should be risk stratified by pretest clinical probability, and low‐probability patients should undergo intermediate testing with _D‐dimer prior to CTPA. Implementation of a similar clinical algorithm at our facility would likely decrease the number of CTPAs ordered. If all patients presenting at our facility with signs and symptoms raising concern for VTE were first risk‐stratified by pretest clinical probability, and all low‐probability patients underwent highly‐sensitive _D‐dimer testing as an initial step, fewer CTPAs would be performed on low‐probability patients. The largest group of patients in our study were low probability; therefore, decreasing CTPA in this group could have a significant effect on our institution.

The retrospective nature of our study resulted in the following limitations. It is impossible to determine how the ordering provider viewed the patient's pretest probability. In most of the medical records, a pretest clinical probability was not documented. We attempted to validate the ordering provider's decision by being as generous as possible in applying points to the Wells Score. For example, if a patient had a remote history of cancer and the ordering provider documented this as a risk factor for VTE, the point value for cancer was given even though the Wells Score has a much narrower definition of this category.10 This practice favors assigning patients a potentially higher clinical probability and may have increased the number of patients designated as intermediate and high clinical probability in our study.

Our hospital primarily relies on CTPA with lower extremity venogram as the diagnostic test for VTE. Indeterminate tests may have occurred and thus falsely lowered the number of VTEs diagnosed. However, no patient with a negative CTPA was diagnosed with VTE by any modality in the 3 months after their initial study at our institution; a diagnosis of VTE could have been made at another hospital. The Simplified Wells Score uses both objective and subjective components to arrive at a point total. Our results might be different if newer algorithms, such as the Revised Geneva Score,16 which relies only on objective measurements, had been used.

CONCLUSIONS

The reliance on CTPA alone to exclude a potentially life‐threatening illness without additional risk stratification or clinical information leads to overuse of this test in patients with very low to no clinical risk for VTE and a low rate of diagnosed VTE. Implementation of a clinical algorithm for the diagnosis of suspected VTE may eliminate the need for many CTPAs, improving the yield of this test without compromising patient safety, especially at institutions with a low prevalence of PE.

Approximately 10 million patients present to emergency departments each year with symptoms raising concern of thromboembolism (VTE).1 The current gold standard for diagnosis of VTE is pulmonary angiography.2 As this study is invasive, alternative imaging protocols have been sought. CTPA, when combined with measures of pretest probability, equals or surpasses the ability of pulmonary angiography to detect VTE and can improve the ability of clinicians to rule out VTE.38 In a study of 930 patients, application of clinical rules in addition to _D‐dimer testing decreased the number of CTPAs ordered by 50%.9 One of the most common clinical rule sets is the Wells Score, which relies on historical features related to the risk of DVT/VTE and physical examination findings.10, 11

Other institutions have demonstrated an increase in the number of CTPAs ordered and VTE diagnoses since the study became widely available.13 Based on the observation of an increasing number of CTPAs ordered at our institution without an increase in the number of VTEs diagnosed, we aimed to ascertain the physician ordering practices for CTPA. We hypothesized that CTPAs were ordered at a greater frequency in a low‐risk population because an institutional clinical algorithm was lacking.

METHODS

Charts of all patients aged 18‐100 with CTPA ordered to rule out acute VTE were retrospectively examined. A Simplified Wells Score was applied using only the information available to the ordering physician at the time the CTPA was performed. Patients were stratified by their Simplified Wells Score to low (0‐1 points), intermediate (2‐6 points), or high (>6 points) pretest clinical probability. A _D‐dimer value, if ordered, was used to further stratify patients based on a positive or negative result. The official radiologic report of the CTPA was used to determine the rate of VTE diagnosis for the study population.

RESULTS

Three hundred and ninety‐four patients were referred for CTPA (Fig. 1). Two hundred and seventy‐nine had adequate clinical data to calculate a Simplified Wells Score and were included in the study. Of the 279 studies included, 75% were ordered through the emergency department and 25% from inpatient services (Table 1). The study patients were stratified according to the Simplified Wells criteria: 184 patients (66%) had low clinical probability, 91 (33%) had intermediate clinical probability, and 4 (1%) had high clinical probability. Nineteen (7%) patients had a history of DVT or VTE, and 28 (10%) had a history of active cancer at the time of their CTPA. One hundred and twenty‐five of the 279 patients had a _D‐dimer performed (Fig. 2). One hundred and eight were positive, and 17 were negative. Of the 17 patients who had a negative _D‐dimer and underwent CTPA testing, none were diagnosed with VTE. Eighty‐three low‐clinical‐probability patients underwent CTPA without _D‐dimer testing, 4 of whom were diagnosed with VTE.

Figure 1

Figure 2

There were 20 positive CTPAs in the study group (Fig. 3). Review of the records for 3 months after the study of patients whose CTPA was negative disclosed no diagnoses of VTE by other modalities. VTE was diagnosed in 4% of patients in the low‐clinical‐probability group, 12% in the intermediate‐clinical‐probability group, and 25% in the high‐clinical‐probability group. The overall positive CTPA rate was 7.2%.

Figure 3

DISCUSSION

Many studies have examined the application of clinical rule sets in addition to D‐dimer testing and CTPA to exclude acute VTE.39 Most of these studies have shown that the use of an algorithm is safe and frequently reduces referral for CTPA in low‐clinical‐probability patients. However, others have noted that some physicians do not routinely use validated algorithms when making decisions related to patient evaluation.13 Our rate of positive CTPA was low compared with rates reported in the literature.3, 14 We believe the most likely explanation is the large number of low‐clinical‐probability patients who underwent CTPA, possibly because providers do not routinely use a validated clinical algorithm.

When our patient population was risk stratified by Simplified Wells criteria and compared with similar data from published studies, we had a much higher proportion of patients classified as low clinical probability.7, 8, 15 The low‐clinical‐probability group's mean Simplified Wells Score was 0.71; one‐third had a Simplified Wells Score of 0. This reflects a low‐risk population for VTE, supported by the low prevalence of prior DVT/VTE and active cancer in our population.4, 10 The rationale for referring patients with so few risk factors for CTPA is unclear. It is possible that providers used CTPA to evaluate symptoms not clearly explained and obtained the study to look for other diagnoses in addition to VTE. By not applying a clinical algorithm, very‐low‐risk patients underwent CTPA, increasing the number of negative studies and decreasing the overall positive rate.

Not using a clinical algorithm also resulted in indiscriminate _D‐dimer testing. There were 83 patients risk‐stratified as low clinical probability who did not have a _D‐dimer prior to undergoing CTPA. Some of these patients may well have had a negative _D‐dimer, requiring no further workup to rule out VTE. Seventeen patients had a negative _D‐dimer and still underwent CTPA; all these patients were negative for VTE. These aberrations likely occurred from unfamiliarity with use of the _D‐dimer test or doubts about its ability to reliably exclude VTE. Appropriate application of _D‐dimer testing could have decreased the number of CTPAs ordered and increased our overall rate of positive VTE diagnosis.

Perrier et al., Brown et al., and Kelly and Wells all describe different methods of introducing clinical algorithms to aid the diagnosis of VTE.46, 9 All agree that patients should be risk stratified by pretest clinical probability, and low‐probability patients should undergo intermediate testing with _D‐dimer prior to CTPA. Implementation of a similar clinical algorithm at our facility would likely decrease the number of CTPAs ordered. If all patients presenting at our facility with signs and symptoms raising concern for VTE were first risk‐stratified by pretest clinical probability, and all low‐probability patients underwent highly‐sensitive _D‐dimer testing as an initial step, fewer CTPAs would be performed on low‐probability patients. The largest group of patients in our study were low probability; therefore, decreasing CTPA in this group could have a significant effect on our institution.

The retrospective nature of our study resulted in the following limitations. It is impossible to determine how the ordering provider viewed the patient's pretest probability. In most of the medical records, a pretest clinical probability was not documented. We attempted to validate the ordering provider's decision by being as generous as possible in applying points to the Wells Score. For example, if a patient had a remote history of cancer and the ordering provider documented this as a risk factor for VTE, the point value for cancer was given even though the Wells Score has a much narrower definition of this category.10 This practice favors assigning patients a potentially higher clinical probability and may have increased the number of patients designated as intermediate and high clinical probability in our study.

Our hospital primarily relies on CTPA with lower extremity venogram as the diagnostic test for VTE. Indeterminate tests may have occurred and thus falsely lowered the number of VTEs diagnosed. However, no patient with a negative CTPA was diagnosed with VTE by any modality in the 3 months after their initial study at our institution; a diagnosis of VTE could have been made at another hospital. The Simplified Wells Score uses both objective and subjective components to arrive at a point total. Our results might be different if newer algorithms, such as the Revised Geneva Score,16 which relies only on objective measurements, had been used.

CONCLUSIONS

The reliance on CTPA alone to exclude a potentially life‐threatening illness without additional risk stratification or clinical information leads to overuse of this test in patients with very low to no clinical risk for VTE and a low rate of diagnosed VTE. Implementation of a clinical algorithm for the diagnosis of suspected VTE may eliminate the need for many CTPAs, improving the yield of this test without compromising patient safety, especially at institutions with a low prevalence of PE.

Vascular surgery has higher morbidity and mortality than other noncardiac surgeries. Despite the identification of vascular surgery as higher risk, 30‐day mortality for this surgery has remained at 3%10%. Few studies have examined longer‐term outcomes, but higher mortality rates have been reported, for example, 10%30% 6 months after surgery, 20%40% 1 year after surgery, and 30%50% 5 years after surgery.15 Postoperative adverse events have been found to be highly correlated with perioperative ischemia and infarction.68 Perioperative beta‐blockers have been widely studied and have been shown to benefit patients undergoing noncardiac surgery generally and vascular surgery specifically.9, 10 However, 2 recent trials of perioperative beta‐blockers in noncardiac and vascular surgery patients failed to show an association with 18‐month and 30‐day postoperative morbidity and mortality, respectively.11, 12 In addition, the authors of a recent meta‐analysis of perioperative beta‐blockers suggested more studies were needed.13 Furthermore, there have been promising new data on the use of perioperative statins.1418 Finally, as a recent clinical trial of revascularization before vascular surgery did not demonstrate an advantage over medical management, the identification of which perioperative medicines improve postoperative outcomes and in what combinations becomes even more important.19 We sought to ascertain if the ambulatory use of statins and/or beta‐blockers within 30 days of surgery was associated with a reduction in long‐term mortality.

METHODS