Marian Renvall, MS

Patient Population/Setting

This was a prospective study of patients admitted to either the medical/cardiac intensive care unit (MICU/CCU) or surgical intensive care unit (SICU) at an academic medical facility and placed on infusion insulin for >24 hours. The Institutional Review Board (IRB) approved the study for prospective chart review and anonymous results reporting without individual consent.

Patients in the SICU were initiated on infusion insulin after 2 blood glucose readings were above 150 mg/dL, whereas initiation was left to the discretion of the attending physician in the MICU/CCU. A computerized system created in‐house recommends insulin infusion rates based on point‐of‐care (POC) glucose measurements with a target range of 91 mg/dL to 150 mg/dL.

Inclusion/Exclusion Criteria

All patients on continuous insulin infusion admitted to the SICU or the MICU/CCU between May 2008 and September 2008 were evaluated for the study (Figure 1). Patients were excluded from analysis if they were on the infusion for less than 24 hours, had a liver transplant, were discharged within 48 hours of transition, were made comfort care or transitioned to an insulin pump. All other patients were included in the final analysis.

Figure 1

Transition Protocol

Data Collection/Monitoring

A multidisciplinary team consisting of hospitalists, ICU pharmacists, critical care physicians and nursing representatives was assembled during the study period. This team was responsible for protocol implementation, data collection, and surveillance of patient response to the protocol. Educational sessions with house staff and nurses in each unit were held prior to the beginning of the study as well as continued monthly educational efforts during the study. In addition, biweekly huddles to review ongoing patient transitions as well as more formal monthly reviews were held.

The primary objective was to improve glycemic control, defined as the mean daily glucose, during the first 48 hours post transition without a significant increase in the percentage of patients with hypoglycemia (41‐70 mg/dL) or severe hypoglycemia (40 mg/dL). Secondary endpoints included the percent of patients with severe hyperglycemia (300 mg/dL), length of stay (LOS) calculated from the day of transition, number of restarts back onto infusion insulin within 72 hours of transition, and day‐weighted glucose mean up to 12 days following transition for patients with diabetes.

Glucose values were collected and averaged over 6‐hour periods for 48 hours post transition. For patients with diabetes, POC glucose values were collected up to 12 days of hospitalization. Day‐weighted means were obtained by calculating the mean glucose for each hospital day, averaged across all hospital days.12

Analysis

Subjects were divided by the presence or absence of diabetes. Those with diabetes were recommended to receive basal SC insulin during the transition period. Within each group, subjects were further divided by adherence to the protocol. Failure to transition per protocol was defined as: not receiving at least 80% of the recommended basal insulin dose, receiving the initial dose of insulin after the drip was discontinued, or receiving basal insulin when none was recommended.

Descriptive statistics within subgroups comparing age, gender, LOS by analysis of variance for continuous data and by chi‐square for nominal data, were compared. Twenty‐four and 48‐hour post transition mean glucose values and the 12 day weighted‐mean glucose were compared using analysis of variance (Stata ver. 10). All data are expressed as mean standard deviation with a significance value established at P < 0.05.

Patients With Diabetes

(Table 1: Patient Demographics; Table 2: Insulin Use and Glycemic Control; Figure 2: Transition Graph).

Figure 2

A total of 62 individual patients accounted for 72 separate transitions in patients with diabetes based on past medical history or an A1c 6% (n = 14). Of these 72 transitions, 33 (46%) adhered to the protocol while the remaining 39 (54%) transitions varied from the protocol at the treatment team's discretion. Despite similar insulin infusion rates and mean glucose values pretransition, patients with diabetes following the protocol had better glycemic control at both 24 hours and 48 hours after transition than those patients transitioned without the protocol. Day 1 mean blood glucose was 168 mg/dL vs. 211 mg/dL (P = <0.001) and day 2 mean blood glucose was 176 mg/dL vs. 218 mg/dL (P = <0.001) in protocol vs. nonprotocol patients with diabetes respectively (Figure 2).

There was a severe hypoglycemic event (40 mg/dL) in 1 patient with diabetes following the protocol and 1 patient not following the protocol within 48 hours of transition. Both events were secondary to nutritional‐insulin mismatch with emesis after insulin in one case and tube feeds being held in the second case. These findings were consistent with our prior examination of hypoglycemia cases.13 Severe hyperglycemia (glucose 300mg/dL) occurred in 5 (15 %) patients following the protocol vs. 19 (49%) patients not following protocol (P = 0.002.) Patients with diabetes following the protocol received significantly more insulin in the first 24 hours (mean of 65 units vs. 27 units, P 0.001) and 24 to 48 hours after transition (mean of 61 units vs. 28 units, p0.001) than those not following protocol.

An alternate method used at our institution and others14, 15 to calculate TDD is based on the patient's weight and body habitus. When we compared the projected TDD based on weight with the TDD using the transition protocol, we found that the weight based method was much less aggressive. For patients following the protocol, the weight based method projected a mean TDD of 46.3 16.9 units whereas the protocol projected a mean TDD of 65 33.2 units (P = 0.001).

Patients with diabetes following protocol received basal insulin an average of 1.13 hours prior to discontinuing the insulin infusion versus 11.6 hours after for those not following protocol.

Three patients with diabetes following the protocol and 3 patients with diabetes not following the protocol were restarted on infusion insulin within 72 hours of transition.

LOS from final transition to discharge was similar between protocol vs. nonprotocol patients (14.6 vs. 14 days, P = 0.836).

Figure 3 demonstrates that when used correctly, the protocol provides an extended period of glycemic control up to 12 days post transition. Patients transitioned per protocol had a day‐weighted mean glucose of 155 mg/dL vs. 184 mg/dL (P = 0.043) in patients not following protocol. There was only 1 glucose value less than 40 mg/dL between days 2 to 12 in the protocol group.

Figure 3

Patients Without Diabetes

Of the 39 individual patients without diabetes there were 42 transition events, 33 transitions (78.6%) were per protocol and placed on correctional insulin only. The remaining 9 transitions failed to follow protocol in that basal insulin was prescribed, but these patients maintained comparable glycemic control without an increase in hypoglycemic events. Following transition, patients without diabetes on protocol maintained a mean glucose of 150 mg/dL in the first 24 hours and 153 mg/dL in 24 to 48 hours post transition. They required a mean daily correctional insulin dose of 3.2 units on Day 1 and 2.8 units on Day 2 despite having an average drip rate of 2.3 units/hour at the time of transition (Table 2). There were no severe hypoglycemic events and 80% of blood sugars were within the goal range of 80 mg/dL to 180 mg/dL. Only 1 patient had a single blood glucose of >300mg/dL. No patient was restarted on infusion insulin once transitioned.

Patients without diabetes had a longer LOS after transition off of infusion insulin when compared to their diabetic counterparts (22 vs. 14 days).

Patient Population/Setting

This was a prospective study of patients admitted to either the medical/cardiac intensive care unit (MICU/CCU) or surgical intensive care unit (SICU) at an academic medical facility and placed on infusion insulin for >24 hours. The Institutional Review Board (IRB) approved the study for prospective chart review and anonymous results reporting without individual consent.

Patients in the SICU were initiated on infusion insulin after 2 blood glucose readings were above 150 mg/dL, whereas initiation was left to the discretion of the attending physician in the MICU/CCU. A computerized system created in‐house recommends insulin infusion rates based on point‐of‐care (POC) glucose measurements with a target range of 91 mg/dL to 150 mg/dL.

Inclusion/Exclusion Criteria

All patients on continuous insulin infusion admitted to the SICU or the MICU/CCU between May 2008 and September 2008 were evaluated for the study (Figure 1). Patients were excluded from analysis if they were on the infusion for less than 24 hours, had a liver transplant, were discharged within 48 hours of transition, were made comfort care or transitioned to an insulin pump. All other patients were included in the final analysis.

Figure 1

Transition Protocol

Data Collection/Monitoring

A multidisciplinary team consisting of hospitalists, ICU pharmacists, critical care physicians and nursing representatives was assembled during the study period. This team was responsible for protocol implementation, data collection, and surveillance of patient response to the protocol. Educational sessions with house staff and nurses in each unit were held prior to the beginning of the study as well as continued monthly educational efforts during the study. In addition, biweekly huddles to review ongoing patient transitions as well as more formal monthly reviews were held.

The primary objective was to improve glycemic control, defined as the mean daily glucose, during the first 48 hours post transition without a significant increase in the percentage of patients with hypoglycemia (41‐70 mg/dL) or severe hypoglycemia (40 mg/dL). Secondary endpoints included the percent of patients with severe hyperglycemia (300 mg/dL), length of stay (LOS) calculated from the day of transition, number of restarts back onto infusion insulin within 72 hours of transition, and day‐weighted glucose mean up to 12 days following transition for patients with diabetes.

Glucose values were collected and averaged over 6‐hour periods for 48 hours post transition. For patients with diabetes, POC glucose values were collected up to 12 days of hospitalization. Day‐weighted means were obtained by calculating the mean glucose for each hospital day, averaged across all hospital days.12

Analysis

Subjects were divided by the presence or absence of diabetes. Those with diabetes were recommended to receive basal SC insulin during the transition period. Within each group, subjects were further divided by adherence to the protocol. Failure to transition per protocol was defined as: not receiving at least 80% of the recommended basal insulin dose, receiving the initial dose of insulin after the drip was discontinued, or receiving basal insulin when none was recommended.

Descriptive statistics within subgroups comparing age, gender, LOS by analysis of variance for continuous data and by chi‐square for nominal data, were compared. Twenty‐four and 48‐hour post transition mean glucose values and the 12 day weighted‐mean glucose were compared using analysis of variance (Stata ver. 10). All data are expressed as mean standard deviation with a significance value established at P < 0.05.

Patients With Diabetes

(Table 1: Patient Demographics; Table 2: Insulin Use and Glycemic Control; Figure 2: Transition Graph).

Figure 2

A total of 62 individual patients accounted for 72 separate transitions in patients with diabetes based on past medical history or an A1c 6% (n = 14). Of these 72 transitions, 33 (46%) adhered to the protocol while the remaining 39 (54%) transitions varied from the protocol at the treatment team's discretion. Despite similar insulin infusion rates and mean glucose values pretransition, patients with diabetes following the protocol had better glycemic control at both 24 hours and 48 hours after transition than those patients transitioned without the protocol. Day 1 mean blood glucose was 168 mg/dL vs. 211 mg/dL (P = <0.001) and day 2 mean blood glucose was 176 mg/dL vs. 218 mg/dL (P = <0.001) in protocol vs. nonprotocol patients with diabetes respectively (Figure 2).

There was a severe hypoglycemic event (40 mg/dL) in 1 patient with diabetes following the protocol and 1 patient not following the protocol within 48 hours of transition. Both events were secondary to nutritional‐insulin mismatch with emesis after insulin in one case and tube feeds being held in the second case. These findings were consistent with our prior examination of hypoglycemia cases.13 Severe hyperglycemia (glucose 300mg/dL) occurred in 5 (15 %) patients following the protocol vs. 19 (49%) patients not following protocol (P = 0.002.) Patients with diabetes following the protocol received significantly more insulin in the first 24 hours (mean of 65 units vs. 27 units, P 0.001) and 24 to 48 hours after transition (mean of 61 units vs. 28 units, p0.001) than those not following protocol.

An alternate method used at our institution and others14, 15 to calculate TDD is based on the patient's weight and body habitus. When we compared the projected TDD based on weight with the TDD using the transition protocol, we found that the weight based method was much less aggressive. For patients following the protocol, the weight based method projected a mean TDD of 46.3 16.9 units whereas the protocol projected a mean TDD of 65 33.2 units (P = 0.001).

Patients with diabetes following protocol received basal insulin an average of 1.13 hours prior to discontinuing the insulin infusion versus 11.6 hours after for those not following protocol.

Three patients with diabetes following the protocol and 3 patients with diabetes not following the protocol were restarted on infusion insulin within 72 hours of transition.

LOS from final transition to discharge was similar between protocol vs. nonprotocol patients (14.6 vs. 14 days, P = 0.836).

Figure 3 demonstrates that when used correctly, the protocol provides an extended period of glycemic control up to 12 days post transition. Patients transitioned per protocol had a day‐weighted mean glucose of 155 mg/dL vs. 184 mg/dL (P = 0.043) in patients not following protocol. There was only 1 glucose value less than 40 mg/dL between days 2 to 12 in the protocol group.

Figure 3

Patients Without Diabetes

Of the 39 individual patients without diabetes there were 42 transition events, 33 transitions (78.6%) were per protocol and placed on correctional insulin only. The remaining 9 transitions failed to follow protocol in that basal insulin was prescribed, but these patients maintained comparable glycemic control without an increase in hypoglycemic events. Following transition, patients without diabetes on protocol maintained a mean glucose of 150 mg/dL in the first 24 hours and 153 mg/dL in 24 to 48 hours post transition. They required a mean daily correctional insulin dose of 3.2 units on Day 1 and 2.8 units on Day 2 despite having an average drip rate of 2.3 units/hour at the time of transition (Table 2). There were no severe hypoglycemic events and 80% of blood sugars were within the goal range of 80 mg/dL to 180 mg/dL. Only 1 patient had a single blood glucose of >300mg/dL. No patient was restarted on infusion insulin once transitioned.

Patients without diabetes had a longer LOS after transition off of infusion insulin when compared to their diabetic counterparts (22 vs. 14 days).

Patient Population/Setting

This was a prospective study of patients admitted to either the medical/cardiac intensive care unit (MICU/CCU) or surgical intensive care unit (SICU) at an academic medical facility and placed on infusion insulin for >24 hours. The Institutional Review Board (IRB) approved the study for prospective chart review and anonymous results reporting without individual consent.

Patients in the SICU were initiated on infusion insulin after 2 blood glucose readings were above 150 mg/dL, whereas initiation was left to the discretion of the attending physician in the MICU/CCU. A computerized system created in‐house recommends insulin infusion rates based on point‐of‐care (POC) glucose measurements with a target range of 91 mg/dL to 150 mg/dL.

Inclusion/Exclusion Criteria

All patients on continuous insulin infusion admitted to the SICU or the MICU/CCU between May 2008 and September 2008 were evaluated for the study (Figure 1). Patients were excluded from analysis if they were on the infusion for less than 24 hours, had a liver transplant, were discharged within 48 hours of transition, were made comfort care or transitioned to an insulin pump. All other patients were included in the final analysis.

Figure 1

Transition Protocol

Data Collection/Monitoring

A multidisciplinary team consisting of hospitalists, ICU pharmacists, critical care physicians and nursing representatives was assembled during the study period. This team was responsible for protocol implementation, data collection, and surveillance of patient response to the protocol. Educational sessions with house staff and nurses in each unit were held prior to the beginning of the study as well as continued monthly educational efforts during the study. In addition, biweekly huddles to review ongoing patient transitions as well as more formal monthly reviews were held.

The primary objective was to improve glycemic control, defined as the mean daily glucose, during the first 48 hours post transition without a significant increase in the percentage of patients with hypoglycemia (41‐70 mg/dL) or severe hypoglycemia (40 mg/dL). Secondary endpoints included the percent of patients with severe hyperglycemia (300 mg/dL), length of stay (LOS) calculated from the day of transition, number of restarts back onto infusion insulin within 72 hours of transition, and day‐weighted glucose mean up to 12 days following transition for patients with diabetes.

Glucose values were collected and averaged over 6‐hour periods for 48 hours post transition. For patients with diabetes, POC glucose values were collected up to 12 days of hospitalization. Day‐weighted means were obtained by calculating the mean glucose for each hospital day, averaged across all hospital days.12

Analysis

Subjects were divided by the presence or absence of diabetes. Those with diabetes were recommended to receive basal SC insulin during the transition period. Within each group, subjects were further divided by adherence to the protocol. Failure to transition per protocol was defined as: not receiving at least 80% of the recommended basal insulin dose, receiving the initial dose of insulin after the drip was discontinued, or receiving basal insulin when none was recommended.

Descriptive statistics within subgroups comparing age, gender, LOS by analysis of variance for continuous data and by chi‐square for nominal data, were compared. Twenty‐four and 48‐hour post transition mean glucose values and the 12 day weighted‐mean glucose were compared using analysis of variance (Stata ver. 10). All data are expressed as mean standard deviation with a significance value established at P < 0.05.

Patients With Diabetes

(Table 1: Patient Demographics; Table 2: Insulin Use and Glycemic Control; Figure 2: Transition Graph).

Figure 2

A total of 62 individual patients accounted for 72 separate transitions in patients with diabetes based on past medical history or an A1c 6% (n = 14). Of these 72 transitions, 33 (46%) adhered to the protocol while the remaining 39 (54%) transitions varied from the protocol at the treatment team's discretion. Despite similar insulin infusion rates and mean glucose values pretransition, patients with diabetes following the protocol had better glycemic control at both 24 hours and 48 hours after transition than those patients transitioned without the protocol. Day 1 mean blood glucose was 168 mg/dL vs. 211 mg/dL (P = <0.001) and day 2 mean blood glucose was 176 mg/dL vs. 218 mg/dL (P = <0.001) in protocol vs. nonprotocol patients with diabetes respectively (Figure 2).

There was a severe hypoglycemic event (40 mg/dL) in 1 patient with diabetes following the protocol and 1 patient not following the protocol within 48 hours of transition. Both events were secondary to nutritional‐insulin mismatch with emesis after insulin in one case and tube feeds being held in the second case. These findings were consistent with our prior examination of hypoglycemia cases.13 Severe hyperglycemia (glucose 300mg/dL) occurred in 5 (15 %) patients following the protocol vs. 19 (49%) patients not following protocol (P = 0.002.) Patients with diabetes following the protocol received significantly more insulin in the first 24 hours (mean of 65 units vs. 27 units, P 0.001) and 24 to 48 hours after transition (mean of 61 units vs. 28 units, p0.001) than those not following protocol.

An alternate method used at our institution and others14, 15 to calculate TDD is based on the patient's weight and body habitus. When we compared the projected TDD based on weight with the TDD using the transition protocol, we found that the weight based method was much less aggressive. For patients following the protocol, the weight based method projected a mean TDD of 46.3 16.9 units whereas the protocol projected a mean TDD of 65 33.2 units (P = 0.001).

Patients with diabetes following protocol received basal insulin an average of 1.13 hours prior to discontinuing the insulin infusion versus 11.6 hours after for those not following protocol.

Three patients with diabetes following the protocol and 3 patients with diabetes not following the protocol were restarted on infusion insulin within 72 hours of transition.

LOS from final transition to discharge was similar between protocol vs. nonprotocol patients (14.6 vs. 14 days, P = 0.836).

Figure 3 demonstrates that when used correctly, the protocol provides an extended period of glycemic control up to 12 days post transition. Patients transitioned per protocol had a day‐weighted mean glucose of 155 mg/dL vs. 184 mg/dL (P = 0.043) in patients not following protocol. There was only 1 glucose value less than 40 mg/dL between days 2 to 12 in the protocol group.

Figure 3

Patients Without Diabetes

Of the 39 individual patients without diabetes there were 42 transition events, 33 transitions (78.6%) were per protocol and placed on correctional insulin only. The remaining 9 transitions failed to follow protocol in that basal insulin was prescribed, but these patients maintained comparable glycemic control without an increase in hypoglycemic events. Following transition, patients without diabetes on protocol maintained a mean glucose of 150 mg/dL in the first 24 hours and 153 mg/dL in 24 to 48 hours post transition. They required a mean daily correctional insulin dose of 3.2 units on Day 1 and 2.8 units on Day 2 despite having an average drip rate of 2.3 units/hour at the time of transition (Table 2). There were no severe hypoglycemic events and 80% of blood sugars were within the goal range of 80 mg/dL to 180 mg/dL. Only 1 patient had a single blood glucose of >300mg/dL. No patient was restarted on infusion insulin once transitioned.

Patients without diabetes had a longer LOS after transition off of infusion insulin when compared to their diabetic counterparts (22 vs. 14 days).

Study Design

We developed, implemented, and refined a VTE prevention protocol and examined the impact of our efforts. We observed adult inpatients on a longitudinal basis for the prevalence of adequate VTE prophylaxis and for the incidence of HA VTE throughout a 36‐month period from calendar year 2005 through 2007, and performed a retrospective analysis for any potential adverse effects of increased VTE prophylaxis. The project adhered to the HIPAA requirements for privacy involving health‐related data from human research participants. The study was approved by the Institutional Review Board of the University of California, San Diego, which waived the requirement for individual patient informed consent.

We included all hospitalized adult patients (medical and surgical services) at our medical center in our observations and interventions, including patients of all ethnic groups, geriatric patients, prisoners, and the socially and economically disadvantaged in our population. Exclusion criteria were age under 14 years, and hospitalization on Psychiatry or Obstetrics/Gynecology services.

Development of a VTE Risk‐assessment Model and VTE Prevention Protocol

A core multidisciplinary team with hospitalists, pulmonary critical care VTE experts, pharmacists, nurses, and information specialists was formed. After gaining administrative support for standardization, we worked with medical staff leaders to gain consensus on a VTE prevention protocol for all medical and surgical areas from mid‐2005 through mid‐2006. The VTE prevention protocol included the elements of VTE risk stratification, definitions of adequate VTE prevention measures linked to the level of VTE risk, and definitions for contraindications to pharmacologic prophylactic measures. We piloted risk‐assessment model (RAM) drafts for ease of use and clarity, using rapid cycle feedback from pharmacy residents, house staff, and medical staff attending physicians. Models often cited in the literature15, 18 that include point‐based scoring of VTE risk factors (with prophylaxis choices hinging on the additive sum of scoring) were rejected based on the pilot experience.

We adopted a simple model with 3 levels of VTE risk that could be completed by the physician in seconds, and then proceeded to integrate this RAM into standardized data collection instruments and eventually (April 2006) into a computerized provider order entry (CPOE) order set (Siemmens Invision v26). Each level of VTE risk was firmly linked to a menu of acceptable prophylaxis options (Table 1). Simple text cues were used to define risk assessment, with more exhaustive listings of risk factors being relegated to accessible reference tables.

Intermittent pneumatic compression devices were endorsed as an adjunct in all patients in the highest risk level, and as the primary method in patients with contraindications to pharmacologic prophylaxis. Aspirin was deemed an inappropriate choice for VTE prophylaxis. Subcutaneous unfractionated or low‐molecular‐weight heparin were endorsed as the primary method of prophylaxis for the majority of patients without contraindications.

Integration of the VTE Protocol into Order Sets

An essential strategy for the success of the VTE protocol included integrating guidance for the physician into the flow of patient care, via standardized order sets. The CPOE VTE prevention order set was modular by design, as opposed to a stand alone design. After conferring with appropriate stakeholders, preexisting and nonstandardized prompts for VTE prophylaxis were removed from commonly used order sets, and the standardized module was inserted in its place. This allowed for integration of the standardized VTE prevention module into all admission and transfer order sets, essentially insuring that all patients admitted or transferred within the medical center would be exposed to the protocol. Physicians using a variety of admission and transfer order sets were prompted to select each patient's risk for VTE, and declare the presence or absence of contraindications to pharmacologic prophylaxis. Only the VTE prevention options most appropriate for the patient's VTE and anticoagulation risk profile were presented as the default choice for VTE prophylaxis. Explicit designation of VTE risk level and a prophylaxis choice were presented in a hard stop mechanism, and utilization of these orders was therefore mandatory, not optional. Proper use (such as the proper classification of VTE risk by the ordering physician) was actively monitored on an auditing basis, and order sets were modified occasionally on the basis of subjective and objective feedback.

Assessment of VTE Risk Assessment Interobserver Agreement

Data from 150 randomly selected patients from the audit pool (from late 2005 through mid‐2006) were abstracted by the nurse practitioner in a detailed manner. Five independent reviewers assessed each patient for VTE risk level, and for a determination of whether or not they were on adequate VTE prophylaxis on the day of the audit per protocol. Interobserver agreement was calculated for these parameters using kappa scores.

Prospective Monitoring of Adequate VTE Prophylaxis

A daily medical center inpatient census report of eligible patients in the medical center for >48 hours was downloaded into an Microsoft Excel spreadsheet, with each patient assigned a consecutive number. The Excel random number generator plug‐in function was used to generate a randomly sequenced list of the patients. The research nurse practitioner targeted serial patients on the list for further study, until she accomplished the requisite number of audits each day. The mean number of audits per month declined over the study years as the trends stabilized and as grant funding expired, but remained robust throughout (2005: 107 audits per month; 2006: 80 audits per month; and 2007: 57 audits per month).

The data collected on each patient randomly selected for audit included age, gender, location, service, date and time of review, and date of admission. The audit VTE RAM (identical to the VTE RAM incorporated into the order set), was used to classify each patient's VTE risk as low, moderate, or high. For each audit, we determined if the patient was on an adequate VTE prevention regimen consistent with our protocol, given their VTE risk level, demographics, and absence or presence of contraindications to pharmacologic prophylaxis. All questionable cases were reviewed by at least 2 physicians at weekly meetings with a final consensus determination. Adequacy of the VTE regimen was judged by orders entered on the day of the audit, but we also noted whether or not ordered intermittent compression devices were in place and functioning at the time of the audit.

Prospective (Concurrent) Discovery and Analysis of VTE Cases

The team nurse practitioner used the PACS radiology reporting and archival system (IMPAX version 4.5; AGFA Healthcare Informatics, Greenville, SC) to identify all new diagnoses of VTE, in the process described below.

Procedure codes for following studies were entered into the IMPAX search engine to locate all such exams performed in the previous 1 to 3 days:

• 1

  Ultrasound exams of the neck, upper extremities, and lower extremities;

• 2

  Computed tomography (CT) angiograms of the chest;

• 3

  Ventilation/perfusion nuclear medicine scans; and

• 4

  Pulmonary angiograms.

Negative studies and studies that revealed unchanged chronic thromboses were excluded, while clots with a chronic appearance but no evidence of prior diagnosis were included. Iliofemoral, popliteal, calf vein, subclavian, internal and external jugular vein, and axillary vein thromboses were therefore included, as were all PEs. Less common locations, such as renal vein and cavernous sinus thromboses, were excluded. The improvement/research team exerted no influence over decisions about whether or not testing was done.

Each new case of VTE was then classified as HA VTE or community‐acquired VTE. A new VTE was classified as HA if the diagnosis was first suspected and made in the hospital. A newly diagnosed VTE was also classified as HA if the VTE was suspected in the ambulatory setting, but the patient had been hospitalized within the arbitrary window of the preceding 30 days.

Each new diagnosis of HA VTE was reviewed by core members of the multidisciplinary support team. This investigation included a determination of whether the patient was on an adequate VTE prophylaxis regimen at the time of the HA VTE, using the RAM and linked prophylaxis menu described above. The VTE prevention regimen ordered at the time the inpatient developed the HA VTE was classified as adherent or nonadherent to the University of California, San Diego (UCSD) protocol: patients who developed VTE when on suboptimal prophylaxis per protocol were classified as having a potentially preventable case. Potentially iatrogenic precipitants of VTE (such as the presence of a central venous catheter or restraints) were also noted. All data were entered into a Microsoft Access database for ease of retrieval and reporting.

All tests for VTE were performed based on clinical signs and symptoms, rather than routine screening, except for the Trauma and Burn services, which also screen for VTE in high‐risk patients per their established screening protocols.

Statistical Analysis of VTE Prophylaxis and HA VTE Cases

Gender differences between cases of VTE and randomly sampled and audited inpatients were examined by chi‐square analysis, and analysis of variance (ANOVA) was used to examine any age or body mass index (BMI) differences between audits and cases.

The unadjusted risk ratio (RR) for adequate prophylaxis was compared by year, with year 2005 being the baseline (comparison) year, by chi‐square analysis.

The unadjusted RR of HA VTE was calculated by dividing the number of cases found in the calendar year by the hospital census of adult inpatients at risk. For each case, a classification for the type of VTE (PE vs. DVT vs. combinations) was recorded. Cases not receiving adequate prophylaxis were categorized as preventable DVT. Unadjusted RRs were calculated for each year by chi‐square analysis, compared to the baseline (2005) year.

All data were analyzed using Stata (version 10; Stata Corp., College Station, TX). Results for the different analysis were considered significant at P < 0.05.

Retrospective Study of Unintentional Adverse Effects

The increase in anticoagulant use accompanying the introduction of the VTE prophylaxis order set warranted an evaluation of any subsequent rise in related adverse events. A study was done to determine the rates of bleeding and heparin‐induced thrombocytopenia (HIT) before and after the implementation of the VTE prophylaxis order set.

A retrospective analysis was conducted to evaluate outcomes in our inpatients from December 2004 through November 2006, with April to November, 2006 representing the post‐order set implementation time period. Any patient with a discharge diagnosis code of e934.2 (anticoagulant‐related adverse event) was selected for study to identify possible bleeding attributable to pharmacologic VTE prophylaxis. Major or minor bleeding attributable to pharmacologic VTE prophylaxis was defined as a bleed occurring 72 hours after receiving pharmacologic VTE prophylaxis. Major bleeding was defined as cerebrovascular, gastrointestinal, retroperitoneal, or overt bleeding with a decrease in hemoglobin 2 mg/dL with clinical symptoms such as hypotension or hypoxia (not associated with hemodialysis) or transfusion of 2 units of packed red blood cells. Minor bleeding was defined as ecchymosis, epistaxis, hematoma, hematuria, hemoptysis, petechiae, or bleeding without a decrease in hemoglobin 2 g/dL.

Possible cases of HIT were identified by screening for a concomitant secondary thrombocytopenia code (287.4). Chart review was then conducted to determine a causal relationship between the use of pharmacologic VTE prophylaxis and adverse events during the hospital stay. HIT attributable to pharmacologic VTE prophylaxis was determined by assessing if patients developed any of the following clinical criteria after receiving pharmacologic VTE prophylaxis: platelet count <150 10⁹/L or 50% decrease from baseline, with or without an associated venous or arterial thrombosis or other sequelae (skin lesions at injection site, acute systemic reaction) and/or a positive heparin‐induced platelet activation (HIPA) test. In order to receive a diagnosis of HIT, thrombocytopenia must have occurred between days 5 to 15 of heparin therapy, unless existing evidence suggested that the patient developed rapid‐onset HIT or delayed‐onset HIT. Rapid‐onset HIT was defined as an abrupt drop in platelet count upon receiving a heparin product, due to heparin exposure within the previous 100 days. Delayed‐onset HIT was defined as HIT that developed several days after discontinuation of heparin. Other evident causes of thrombocytopenia were ruled out.

Statistical Analysis of Retrospective Study of Unintentional Adverse Effects

Regression analysis with chi‐square and ANOVA were used in the analysis of the demographic data. RRs were calculated for the number of cases coded with an anticoagulant‐related adverse event secondary thrombocytopenia before and after the order set implementation.

Educational Efforts and Feedback

Members of the multidisciplinary team presented information on HA VTE and the VTE prevention protocol at Medical and Surgical grand rounds, teaching rounds, and noon conference, averaging 1 educational session per quarter. Feedback and education was provided to physicians and nursing staff when audits revealed that a patient had inadequate prophylaxis with reference to the protocol standard. In addition, these conversations provided on opportunity to explore reasons for nonadherence with the protocol, confusion regarding the VTE RAM, and other barriers to effective prophylaxis, thereby providing guidance for further protocol revision and educational efforts. We adjusted the order set based on active monitoring of order set use and the audit process.

Interobserver Agreement

The VTE RAM interobserver agreement was assessed on 150 patients with 5 observers as described above. The kappa score for the VTE risk level was 0.81. The kappa score for the judgment of whether the patient was on adequate prophylaxis or not was 0.90.

Impact on Percent of Patients with Adequate Prophylaxis (Longitudinal Audits)

Audits of randomly sampled inpatients occurred longitudinally throughout the study period as described above. Based on the intervention, the percent of patients on adequate prophylaxis improved significantly (P < 0.001) by each calendar year (see Table 3), from a baseline of 58% in 2005 to 78% in 2006 (unadjusted relative benefit = 1.35; 95% confidence interval [CI] = 1.28‐1.43), and 93% in 2007 (unadjusted relative benefit = 1.61; 95% CI = 1.52, 1.69). The improvement seen was more marked in the moderate VTE risk patients when compared to the high VTE risk patients. The percent of audited VTE prophylaxis improved from 53% in calendar year (CY) 2005 to 93% in 2007 (unadjusted relative benefit = 1.75; 95% CI = 1.70‐1.81) in the moderate VTE risk group, while the high VTE risk group improved from 83% to 92% in the same time period (unadjusted relative benefit = 1.11; 95% CI = 0.95‐1.25).

Overall, adequate VTE prophylaxis was present in over 98% of audited patients in the last 6 months of 2007, and this high rate has been sustained throughout 2008. Age, ethnicity, and gender were not associated with differential rates of adequate VTE prophylaxis.

Figure 1 is a timeline of interventions and the impact on the prevalence of adequate VTE prophylaxis. The first 7 to 8 months represent the baseline rate 50% to 55% of VTE prophylaxis. In this baseline period, the improvement team was meeting, but had not yet begun meeting with the large variety of medical and surgical service leaders. Consensus‐building sessions with these leaders in the latter part of 2005 through mid‐2006 correlated with improvement in adequate VTE prophylaxis rates to near 70%. The consensus‐building sessions also prepared these varied services for a go live date of the modular order set that was incorporated into all admit and transfer order sets, often replacing preexisting orders referring to VTE prevention measures. The order set resulted in an improvement to 80% adequate prophylaxis, with the incremental improvement occurring virtually overnight with the go live date at the onset of quarter 2 (Q2) of 2006. Monitoring of the order set use confirmed that it was easy and efficient to use, but also revealed that physicians were at times classifying patients as low VTE risk inaccurately, when they possessed qualities that actually qualified them for moderate risk status by our protocol. We therefore inserted a secondary CPOE screen when patients were categorized as low VTE risk, asking the physician to deny or confirm that the patient had no risk factors that qualified them for moderate risk status. This confirmation screen essentially acted as a reminder to the physician to ask Are you sure this patient does not need VTE prophylaxis? This minor modification of the CPOE order set improved adequate VTE prophylaxis rates to 90%. Finally, we asked nurses to evaluate patients who were not on therapeutic or prophylactic doses of anticoagulants. Patients with VTE risk factors but no obvious contraindications generated a note from the nurse to the doctor, prompting the doctor to reassess VTE risk and potential contraindications. This simple intervention raised the percent of audited patients on adequate VTE prophylaxis to 98% in the last 6 months of 2007.

Figure 1

Description of Prospectively Identified VTE

We identified 748 cases of VTE among patients admitted to the medical center over the 36‐month study period; 387 (52%) were community‐acquired VTE. There were 361 HA cases (48% of total cases) over the same time period. There was no difference in age, gender, or BMI between the community‐acquired and hospital‐related VTE.

Of the 361 HA cases, 199 (55%) occurred on Surgical Services and 162 (45%) occurred on Medical Services; 58 (16%) unique patients had pulmonary emboli, while 303 (84%) patients experienced only DVT. Remarkably, almost one‐third of the DVT occurred in the upper extremities (108 upper extremities, 240 lower extremities), and most (80%) of the upper‐extremity DVT were associated with central venous catheters.

Of 361 HA VTE cases, 292 (81%) occurred in those in the moderate VTE risk category, 69 HA VTE cases occurred in high‐risk category patients (19%), and no VTE occurred in patients in the low‐risk category.

Improvement in HA VTE

HA VTE were identified and each case analyzed on an ongoing basis over the entire 3 year study period, as described above. Table 4 depicts a comparison of HA VTE on a year‐to‐year basis and the impact of the VTE prevention protocol on the incidence of HA VTE. In 2007 (the first full CY after the implementation of the order set) there was a 39% relative risk reduction (RRR) in the risk of experiencing an HA VTE. The reduction in the risk of preventable HA VTE was even more marked (RRR = 86%; 7 preventable VTE in 2007, compared to 44 in baseline year of 2005; RR = 0.14; 95% CI = 0.06‐0.31).

Retrospective Analysis of Impact on HIT and Bleeding

There were no statistically significant differences in the number of cases coded for an anticoagulant‐related bleed or secondary thrombocytopenia (Table 5). Chart review revealed there were 2 cases of minor bleeding attributable to pharmacologic VTE prophylaxis before the order set implementation. There were no cases after implementation. No cases of HIT attributable to pharmacologic VTE prophylaxis were identified in either study period, with all cases being attributed to therapeutic anticoagulation.

Study Design

We developed, implemented, and refined a VTE prevention protocol and examined the impact of our efforts. We observed adult inpatients on a longitudinal basis for the prevalence of adequate VTE prophylaxis and for the incidence of HA VTE throughout a 36‐month period from calendar year 2005 through 2007, and performed a retrospective analysis for any potential adverse effects of increased VTE prophylaxis. The project adhered to the HIPAA requirements for privacy involving health‐related data from human research participants. The study was approved by the Institutional Review Board of the University of California, San Diego, which waived the requirement for individual patient informed consent.

We included all hospitalized adult patients (medical and surgical services) at our medical center in our observations and interventions, including patients of all ethnic groups, geriatric patients, prisoners, and the socially and economically disadvantaged in our population. Exclusion criteria were age under 14 years, and hospitalization on Psychiatry or Obstetrics/Gynecology services.

Development of a VTE Risk‐assessment Model and VTE Prevention Protocol

A core multidisciplinary team with hospitalists, pulmonary critical care VTE experts, pharmacists, nurses, and information specialists was formed. After gaining administrative support for standardization, we worked with medical staff leaders to gain consensus on a VTE prevention protocol for all medical and surgical areas from mid‐2005 through mid‐2006. The VTE prevention protocol included the elements of VTE risk stratification, definitions of adequate VTE prevention measures linked to the level of VTE risk, and definitions for contraindications to pharmacologic prophylactic measures. We piloted risk‐assessment model (RAM) drafts for ease of use and clarity, using rapid cycle feedback from pharmacy residents, house staff, and medical staff attending physicians. Models often cited in the literature15, 18 that include point‐based scoring of VTE risk factors (with prophylaxis choices hinging on the additive sum of scoring) were rejected based on the pilot experience.

We adopted a simple model with 3 levels of VTE risk that could be completed by the physician in seconds, and then proceeded to integrate this RAM into standardized data collection instruments and eventually (April 2006) into a computerized provider order entry (CPOE) order set (Siemmens Invision v26). Each level of VTE risk was firmly linked to a menu of acceptable prophylaxis options (Table 1). Simple text cues were used to define risk assessment, with more exhaustive listings of risk factors being relegated to accessible reference tables.

Intermittent pneumatic compression devices were endorsed as an adjunct in all patients in the highest risk level, and as the primary method in patients with contraindications to pharmacologic prophylaxis. Aspirin was deemed an inappropriate choice for VTE prophylaxis. Subcutaneous unfractionated or low‐molecular‐weight heparin were endorsed as the primary method of prophylaxis for the majority of patients without contraindications.

Integration of the VTE Protocol into Order Sets

An essential strategy for the success of the VTE protocol included integrating guidance for the physician into the flow of patient care, via standardized order sets. The CPOE VTE prevention order set was modular by design, as opposed to a stand alone design. After conferring with appropriate stakeholders, preexisting and nonstandardized prompts for VTE prophylaxis were removed from commonly used order sets, and the standardized module was inserted in its place. This allowed for integration of the standardized VTE prevention module into all admission and transfer order sets, essentially insuring that all patients admitted or transferred within the medical center would be exposed to the protocol. Physicians using a variety of admission and transfer order sets were prompted to select each patient's risk for VTE, and declare the presence or absence of contraindications to pharmacologic prophylaxis. Only the VTE prevention options most appropriate for the patient's VTE and anticoagulation risk profile were presented as the default choice for VTE prophylaxis. Explicit designation of VTE risk level and a prophylaxis choice were presented in a hard stop mechanism, and utilization of these orders was therefore mandatory, not optional. Proper use (such as the proper classification of VTE risk by the ordering physician) was actively monitored on an auditing basis, and order sets were modified occasionally on the basis of subjective and objective feedback.

Assessment of VTE Risk Assessment Interobserver Agreement

Data from 150 randomly selected patients from the audit pool (from late 2005 through mid‐2006) were abstracted by the nurse practitioner in a detailed manner. Five independent reviewers assessed each patient for VTE risk level, and for a determination of whether or not they were on adequate VTE prophylaxis on the day of the audit per protocol. Interobserver agreement was calculated for these parameters using kappa scores.

Prospective Monitoring of Adequate VTE Prophylaxis

A daily medical center inpatient census report of eligible patients in the medical center for >48 hours was downloaded into an Microsoft Excel spreadsheet, with each patient assigned a consecutive number. The Excel random number generator plug‐in function was used to generate a randomly sequenced list of the patients. The research nurse practitioner targeted serial patients on the list for further study, until she accomplished the requisite number of audits each day. The mean number of audits per month declined over the study years as the trends stabilized and as grant funding expired, but remained robust throughout (2005: 107 audits per month; 2006: 80 audits per month; and 2007: 57 audits per month).

The data collected on each patient randomly selected for audit included age, gender, location, service, date and time of review, and date of admission. The audit VTE RAM (identical to the VTE RAM incorporated into the order set), was used to classify each patient's VTE risk as low, moderate, or high. For each audit, we determined if the patient was on an adequate VTE prevention regimen consistent with our protocol, given their VTE risk level, demographics, and absence or presence of contraindications to pharmacologic prophylaxis. All questionable cases were reviewed by at least 2 physicians at weekly meetings with a final consensus determination. Adequacy of the VTE regimen was judged by orders entered on the day of the audit, but we also noted whether or not ordered intermittent compression devices were in place and functioning at the time of the audit.

Prospective (Concurrent) Discovery and Analysis of VTE Cases

The team nurse practitioner used the PACS radiology reporting and archival system (IMPAX version 4.5; AGFA Healthcare Informatics, Greenville, SC) to identify all new diagnoses of VTE, in the process described below.

Procedure codes for following studies were entered into the IMPAX search engine to locate all such exams performed in the previous 1 to 3 days:

• 1

  Ultrasound exams of the neck, upper extremities, and lower extremities;

• 2

  Computed tomography (CT) angiograms of the chest;

• 3

  Ventilation/perfusion nuclear medicine scans; and

• 4

  Pulmonary angiograms.

Negative studies and studies that revealed unchanged chronic thromboses were excluded, while clots with a chronic appearance but no evidence of prior diagnosis were included. Iliofemoral, popliteal, calf vein, subclavian, internal and external jugular vein, and axillary vein thromboses were therefore included, as were all PEs. Less common locations, such as renal vein and cavernous sinus thromboses, were excluded. The improvement/research team exerted no influence over decisions about whether or not testing was done.

Each new case of VTE was then classified as HA VTE or community‐acquired VTE. A new VTE was classified as HA if the diagnosis was first suspected and made in the hospital. A newly diagnosed VTE was also classified as HA if the VTE was suspected in the ambulatory setting, but the patient had been hospitalized within the arbitrary window of the preceding 30 days.

Each new diagnosis of HA VTE was reviewed by core members of the multidisciplinary support team. This investigation included a determination of whether the patient was on an adequate VTE prophylaxis regimen at the time of the HA VTE, using the RAM and linked prophylaxis menu described above. The VTE prevention regimen ordered at the time the inpatient developed the HA VTE was classified as adherent or nonadherent to the University of California, San Diego (UCSD) protocol: patients who developed VTE when on suboptimal prophylaxis per protocol were classified as having a potentially preventable case. Potentially iatrogenic precipitants of VTE (such as the presence of a central venous catheter or restraints) were also noted. All data were entered into a Microsoft Access database for ease of retrieval and reporting.

All tests for VTE were performed based on clinical signs and symptoms, rather than routine screening, except for the Trauma and Burn services, which also screen for VTE in high‐risk patients per their established screening protocols.

Statistical Analysis of VTE Prophylaxis and HA VTE Cases

Gender differences between cases of VTE and randomly sampled and audited inpatients were examined by chi‐square analysis, and analysis of variance (ANOVA) was used to examine any age or body mass index (BMI) differences between audits and cases.

The unadjusted risk ratio (RR) for adequate prophylaxis was compared by year, with year 2005 being the baseline (comparison) year, by chi‐square analysis.

The unadjusted RR of HA VTE was calculated by dividing the number of cases found in the calendar year by the hospital census of adult inpatients at risk. For each case, a classification for the type of VTE (PE vs. DVT vs. combinations) was recorded. Cases not receiving adequate prophylaxis were categorized as preventable DVT. Unadjusted RRs were calculated for each year by chi‐square analysis, compared to the baseline (2005) year.

All data were analyzed using Stata (version 10; Stata Corp., College Station, TX). Results for the different analysis were considered significant at P < 0.05.

Retrospective Study of Unintentional Adverse Effects

The increase in anticoagulant use accompanying the introduction of the VTE prophylaxis order set warranted an evaluation of any subsequent rise in related adverse events. A study was done to determine the rates of bleeding and heparin‐induced thrombocytopenia (HIT) before and after the implementation of the VTE prophylaxis order set.

A retrospective analysis was conducted to evaluate outcomes in our inpatients from December 2004 through November 2006, with April to November, 2006 representing the post‐order set implementation time period. Any patient with a discharge diagnosis code of e934.2 (anticoagulant‐related adverse event) was selected for study to identify possible bleeding attributable to pharmacologic VTE prophylaxis. Major or minor bleeding attributable to pharmacologic VTE prophylaxis was defined as a bleed occurring 72 hours after receiving pharmacologic VTE prophylaxis. Major bleeding was defined as cerebrovascular, gastrointestinal, retroperitoneal, or overt bleeding with a decrease in hemoglobin 2 mg/dL with clinical symptoms such as hypotension or hypoxia (not associated with hemodialysis) or transfusion of 2 units of packed red blood cells. Minor bleeding was defined as ecchymosis, epistaxis, hematoma, hematuria, hemoptysis, petechiae, or bleeding without a decrease in hemoglobin 2 g/dL.

Possible cases of HIT were identified by screening for a concomitant secondary thrombocytopenia code (287.4). Chart review was then conducted to determine a causal relationship between the use of pharmacologic VTE prophylaxis and adverse events during the hospital stay. HIT attributable to pharmacologic VTE prophylaxis was determined by assessing if patients developed any of the following clinical criteria after receiving pharmacologic VTE prophylaxis: platelet count <150 10⁹/L or 50% decrease from baseline, with or without an associated venous or arterial thrombosis or other sequelae (skin lesions at injection site, acute systemic reaction) and/or a positive heparin‐induced platelet activation (HIPA) test. In order to receive a diagnosis of HIT, thrombocytopenia must have occurred between days 5 to 15 of heparin therapy, unless existing evidence suggested that the patient developed rapid‐onset HIT or delayed‐onset HIT. Rapid‐onset HIT was defined as an abrupt drop in platelet count upon receiving a heparin product, due to heparin exposure within the previous 100 days. Delayed‐onset HIT was defined as HIT that developed several days after discontinuation of heparin. Other evident causes of thrombocytopenia were ruled out.

Statistical Analysis of Retrospective Study of Unintentional Adverse Effects

Regression analysis with chi‐square and ANOVA were used in the analysis of the demographic data. RRs were calculated for the number of cases coded with an anticoagulant‐related adverse event secondary thrombocytopenia before and after the order set implementation.

Educational Efforts and Feedback

Members of the multidisciplinary team presented information on HA VTE and the VTE prevention protocol at Medical and Surgical grand rounds, teaching rounds, and noon conference, averaging 1 educational session per quarter. Feedback and education was provided to physicians and nursing staff when audits revealed that a patient had inadequate prophylaxis with reference to the protocol standard. In addition, these conversations provided on opportunity to explore reasons for nonadherence with the protocol, confusion regarding the VTE RAM, and other barriers to effective prophylaxis, thereby providing guidance for further protocol revision and educational efforts. We adjusted the order set based on active monitoring of order set use and the audit process.

Interobserver Agreement

The VTE RAM interobserver agreement was assessed on 150 patients with 5 observers as described above. The kappa score for the VTE risk level was 0.81. The kappa score for the judgment of whether the patient was on adequate prophylaxis or not was 0.90.

Impact on Percent of Patients with Adequate Prophylaxis (Longitudinal Audits)

Audits of randomly sampled inpatients occurred longitudinally throughout the study period as described above. Based on the intervention, the percent of patients on adequate prophylaxis improved significantly (P < 0.001) by each calendar year (see Table 3), from a baseline of 58% in 2005 to 78% in 2006 (unadjusted relative benefit = 1.35; 95% confidence interval [CI] = 1.28‐1.43), and 93% in 2007 (unadjusted relative benefit = 1.61; 95% CI = 1.52, 1.69). The improvement seen was more marked in the moderate VTE risk patients when compared to the high VTE risk patients. The percent of audited VTE prophylaxis improved from 53% in calendar year (CY) 2005 to 93% in 2007 (unadjusted relative benefit = 1.75; 95% CI = 1.70‐1.81) in the moderate VTE risk group, while the high VTE risk group improved from 83% to 92% in the same time period (unadjusted relative benefit = 1.11; 95% CI = 0.95‐1.25).

Overall, adequate VTE prophylaxis was present in over 98% of audited patients in the last 6 months of 2007, and this high rate has been sustained throughout 2008. Age, ethnicity, and gender were not associated with differential rates of adequate VTE prophylaxis.

Figure 1 is a timeline of interventions and the impact on the prevalence of adequate VTE prophylaxis. The first 7 to 8 months represent the baseline rate 50% to 55% of VTE prophylaxis. In this baseline period, the improvement team was meeting, but had not yet begun meeting with the large variety of medical and surgical service leaders. Consensus‐building sessions with these leaders in the latter part of 2005 through mid‐2006 correlated with improvement in adequate VTE prophylaxis rates to near 70%. The consensus‐building sessions also prepared these varied services for a go live date of the modular order set that was incorporated into all admit and transfer order sets, often replacing preexisting orders referring to VTE prevention measures. The order set resulted in an improvement to 80% adequate prophylaxis, with the incremental improvement occurring virtually overnight with the go live date at the onset of quarter 2 (Q2) of 2006. Monitoring of the order set use confirmed that it was easy and efficient to use, but also revealed that physicians were at times classifying patients as low VTE risk inaccurately, when they possessed qualities that actually qualified them for moderate risk status by our protocol. We therefore inserted a secondary CPOE screen when patients were categorized as low VTE risk, asking the physician to deny or confirm that the patient had no risk factors that qualified them for moderate risk status. This confirmation screen essentially acted as a reminder to the physician to ask Are you sure this patient does not need VTE prophylaxis? This minor modification of the CPOE order set improved adequate VTE prophylaxis rates to 90%. Finally, we asked nurses to evaluate patients who were not on therapeutic or prophylactic doses of anticoagulants. Patients with VTE risk factors but no obvious contraindications generated a note from the nurse to the doctor, prompting the doctor to reassess VTE risk and potential contraindications. This simple intervention raised the percent of audited patients on adequate VTE prophylaxis to 98% in the last 6 months of 2007.

Figure 1

Description of Prospectively Identified VTE

We identified 748 cases of VTE among patients admitted to the medical center over the 36‐month study period; 387 (52%) were community‐acquired VTE. There were 361 HA cases (48% of total cases) over the same time period. There was no difference in age, gender, or BMI between the community‐acquired and hospital‐related VTE.

Of the 361 HA cases, 199 (55%) occurred on Surgical Services and 162 (45%) occurred on Medical Services; 58 (16%) unique patients had pulmonary emboli, while 303 (84%) patients experienced only DVT. Remarkably, almost one‐third of the DVT occurred in the upper extremities (108 upper extremities, 240 lower extremities), and most (80%) of the upper‐extremity DVT were associated with central venous catheters.

Of 361 HA VTE cases, 292 (81%) occurred in those in the moderate VTE risk category, 69 HA VTE cases occurred in high‐risk category patients (19%), and no VTE occurred in patients in the low‐risk category.

Improvement in HA VTE

HA VTE were identified and each case analyzed on an ongoing basis over the entire 3 year study period, as described above. Table 4 depicts a comparison of HA VTE on a year‐to‐year basis and the impact of the VTE prevention protocol on the incidence of HA VTE. In 2007 (the first full CY after the implementation of the order set) there was a 39% relative risk reduction (RRR) in the risk of experiencing an HA VTE. The reduction in the risk of preventable HA VTE was even more marked (RRR = 86%; 7 preventable VTE in 2007, compared to 44 in baseline year of 2005; RR = 0.14; 95% CI = 0.06‐0.31).

Retrospective Analysis of Impact on HIT and Bleeding

There were no statistically significant differences in the number of cases coded for an anticoagulant‐related bleed or secondary thrombocytopenia (Table 5). Chart review revealed there were 2 cases of minor bleeding attributable to pharmacologic VTE prophylaxis before the order set implementation. There were no cases after implementation. No cases of HIT attributable to pharmacologic VTE prophylaxis were identified in either study period, with all cases being attributed to therapeutic anticoagulation.

Study Design

We developed, implemented, and refined a VTE prevention protocol and examined the impact of our efforts. We observed adult inpatients on a longitudinal basis for the prevalence of adequate VTE prophylaxis and for the incidence of HA VTE throughout a 36‐month period from calendar year 2005 through 2007, and performed a retrospective analysis for any potential adverse effects of increased VTE prophylaxis. The project adhered to the HIPAA requirements for privacy involving health‐related data from human research participants. The study was approved by the Institutional Review Board of the University of California, San Diego, which waived the requirement for individual patient informed consent.

We included all hospitalized adult patients (medical and surgical services) at our medical center in our observations and interventions, including patients of all ethnic groups, geriatric patients, prisoners, and the socially and economically disadvantaged in our population. Exclusion criteria were age under 14 years, and hospitalization on Psychiatry or Obstetrics/Gynecology services.

Development of a VTE Risk‐assessment Model and VTE Prevention Protocol

A core multidisciplinary team with hospitalists, pulmonary critical care VTE experts, pharmacists, nurses, and information specialists was formed. After gaining administrative support for standardization, we worked with medical staff leaders to gain consensus on a VTE prevention protocol for all medical and surgical areas from mid‐2005 through mid‐2006. The VTE prevention protocol included the elements of VTE risk stratification, definitions of adequate VTE prevention measures linked to the level of VTE risk, and definitions for contraindications to pharmacologic prophylactic measures. We piloted risk‐assessment model (RAM) drafts for ease of use and clarity, using rapid cycle feedback from pharmacy residents, house staff, and medical staff attending physicians. Models often cited in the literature15, 18 that include point‐based scoring of VTE risk factors (with prophylaxis choices hinging on the additive sum of scoring) were rejected based on the pilot experience.

We adopted a simple model with 3 levels of VTE risk that could be completed by the physician in seconds, and then proceeded to integrate this RAM into standardized data collection instruments and eventually (April 2006) into a computerized provider order entry (CPOE) order set (Siemmens Invision v26). Each level of VTE risk was firmly linked to a menu of acceptable prophylaxis options (Table 1). Simple text cues were used to define risk assessment, with more exhaustive listings of risk factors being relegated to accessible reference tables.

Intermittent pneumatic compression devices were endorsed as an adjunct in all patients in the highest risk level, and as the primary method in patients with contraindications to pharmacologic prophylaxis. Aspirin was deemed an inappropriate choice for VTE prophylaxis. Subcutaneous unfractionated or low‐molecular‐weight heparin were endorsed as the primary method of prophylaxis for the majority of patients without contraindications.

Integration of the VTE Protocol into Order Sets

An essential strategy for the success of the VTE protocol included integrating guidance for the physician into the flow of patient care, via standardized order sets. The CPOE VTE prevention order set was modular by design, as opposed to a stand alone design. After conferring with appropriate stakeholders, preexisting and nonstandardized prompts for VTE prophylaxis were removed from commonly used order sets, and the standardized module was inserted in its place. This allowed for integration of the standardized VTE prevention module into all admission and transfer order sets, essentially insuring that all patients admitted or transferred within the medical center would be exposed to the protocol. Physicians using a variety of admission and transfer order sets were prompted to select each patient's risk for VTE, and declare the presence or absence of contraindications to pharmacologic prophylaxis. Only the VTE prevention options most appropriate for the patient's VTE and anticoagulation risk profile were presented as the default choice for VTE prophylaxis. Explicit designation of VTE risk level and a prophylaxis choice were presented in a hard stop mechanism, and utilization of these orders was therefore mandatory, not optional. Proper use (such as the proper classification of VTE risk by the ordering physician) was actively monitored on an auditing basis, and order sets were modified occasionally on the basis of subjective and objective feedback.

Assessment of VTE Risk Assessment Interobserver Agreement

Data from 150 randomly selected patients from the audit pool (from late 2005 through mid‐2006) were abstracted by the nurse practitioner in a detailed manner. Five independent reviewers assessed each patient for VTE risk level, and for a determination of whether or not they were on adequate VTE prophylaxis on the day of the audit per protocol. Interobserver agreement was calculated for these parameters using kappa scores.

Prospective Monitoring of Adequate VTE Prophylaxis

A daily medical center inpatient census report of eligible patients in the medical center for >48 hours was downloaded into an Microsoft Excel spreadsheet, with each patient assigned a consecutive number. The Excel random number generator plug‐in function was used to generate a randomly sequenced list of the patients. The research nurse practitioner targeted serial patients on the list for further study, until she accomplished the requisite number of audits each day. The mean number of audits per month declined over the study years as the trends stabilized and as grant funding expired, but remained robust throughout (2005: 107 audits per month; 2006: 80 audits per month; and 2007: 57 audits per month).

The data collected on each patient randomly selected for audit included age, gender, location, service, date and time of review, and date of admission. The audit VTE RAM (identical to the VTE RAM incorporated into the order set), was used to classify each patient's VTE risk as low, moderate, or high. For each audit, we determined if the patient was on an adequate VTE prevention regimen consistent with our protocol, given their VTE risk level, demographics, and absence or presence of contraindications to pharmacologic prophylaxis. All questionable cases were reviewed by at least 2 physicians at weekly meetings with a final consensus determination. Adequacy of the VTE regimen was judged by orders entered on the day of the audit, but we also noted whether or not ordered intermittent compression devices were in place and functioning at the time of the audit.

Prospective (Concurrent) Discovery and Analysis of VTE Cases

The team nurse practitioner used the PACS radiology reporting and archival system (IMPAX version 4.5; AGFA Healthcare Informatics, Greenville, SC) to identify all new diagnoses of VTE, in the process described below.

Procedure codes for following studies were entered into the IMPAX search engine to locate all such exams performed in the previous 1 to 3 days:

• 1

  Ultrasound exams of the neck, upper extremities, and lower extremities;

• 2

  Computed tomography (CT) angiograms of the chest;

• 3

  Ventilation/perfusion nuclear medicine scans; and

• 4

  Pulmonary angiograms.

Negative studies and studies that revealed unchanged chronic thromboses were excluded, while clots with a chronic appearance but no evidence of prior diagnosis were included. Iliofemoral, popliteal, calf vein, subclavian, internal and external jugular vein, and axillary vein thromboses were therefore included, as were all PEs. Less common locations, such as renal vein and cavernous sinus thromboses, were excluded. The improvement/research team exerted no influence over decisions about whether or not testing was done.

Each new case of VTE was then classified as HA VTE or community‐acquired VTE. A new VTE was classified as HA if the diagnosis was first suspected and made in the hospital. A newly diagnosed VTE was also classified as HA if the VTE was suspected in the ambulatory setting, but the patient had been hospitalized within the arbitrary window of the preceding 30 days.

Each new diagnosis of HA VTE was reviewed by core members of the multidisciplinary support team. This investigation included a determination of whether the patient was on an adequate VTE prophylaxis regimen at the time of the HA VTE, using the RAM and linked prophylaxis menu described above. The VTE prevention regimen ordered at the time the inpatient developed the HA VTE was classified as adherent or nonadherent to the University of California, San Diego (UCSD) protocol: patients who developed VTE when on suboptimal prophylaxis per protocol were classified as having a potentially preventable case. Potentially iatrogenic precipitants of VTE (such as the presence of a central venous catheter or restraints) were also noted. All data were entered into a Microsoft Access database for ease of retrieval and reporting.

All tests for VTE were performed based on clinical signs and symptoms, rather than routine screening, except for the Trauma and Burn services, which also screen for VTE in high‐risk patients per their established screening protocols.

Statistical Analysis of VTE Prophylaxis and HA VTE Cases

Gender differences between cases of VTE and randomly sampled and audited inpatients were examined by chi‐square analysis, and analysis of variance (ANOVA) was used to examine any age or body mass index (BMI) differences between audits and cases.

The unadjusted risk ratio (RR) for adequate prophylaxis was compared by year, with year 2005 being the baseline (comparison) year, by chi‐square analysis.

The unadjusted RR of HA VTE was calculated by dividing the number of cases found in the calendar year by the hospital census of adult inpatients at risk. For each case, a classification for the type of VTE (PE vs. DVT vs. combinations) was recorded. Cases not receiving adequate prophylaxis were categorized as preventable DVT. Unadjusted RRs were calculated for each year by chi‐square analysis, compared to the baseline (2005) year.

All data were analyzed using Stata (version 10; Stata Corp., College Station, TX). Results for the different analysis were considered significant at P < 0.05.

Retrospective Study of Unintentional Adverse Effects

The increase in anticoagulant use accompanying the introduction of the VTE prophylaxis order set warranted an evaluation of any subsequent rise in related adverse events. A study was done to determine the rates of bleeding and heparin‐induced thrombocytopenia (HIT) before and after the implementation of the VTE prophylaxis order set.

A retrospective analysis was conducted to evaluate outcomes in our inpatients from December 2004 through November 2006, with April to November, 2006 representing the post‐order set implementation time period. Any patient with a discharge diagnosis code of e934.2 (anticoagulant‐related adverse event) was selected for study to identify possible bleeding attributable to pharmacologic VTE prophylaxis. Major or minor bleeding attributable to pharmacologic VTE prophylaxis was defined as a bleed occurring 72 hours after receiving pharmacologic VTE prophylaxis. Major bleeding was defined as cerebrovascular, gastrointestinal, retroperitoneal, or overt bleeding with a decrease in hemoglobin 2 mg/dL with clinical symptoms such as hypotension or hypoxia (not associated with hemodialysis) or transfusion of 2 units of packed red blood cells. Minor bleeding was defined as ecchymosis, epistaxis, hematoma, hematuria, hemoptysis, petechiae, or bleeding without a decrease in hemoglobin 2 g/dL.

Possible cases of HIT were identified by screening for a concomitant secondary thrombocytopenia code (287.4). Chart review was then conducted to determine a causal relationship between the use of pharmacologic VTE prophylaxis and adverse events during the hospital stay. HIT attributable to pharmacologic VTE prophylaxis was determined by assessing if patients developed any of the following clinical criteria after receiving pharmacologic VTE prophylaxis: platelet count <150 10⁹/L or 50% decrease from baseline, with or without an associated venous or arterial thrombosis or other sequelae (skin lesions at injection site, acute systemic reaction) and/or a positive heparin‐induced platelet activation (HIPA) test. In order to receive a diagnosis of HIT, thrombocytopenia must have occurred between days 5 to 15 of heparin therapy, unless existing evidence suggested that the patient developed rapid‐onset HIT or delayed‐onset HIT. Rapid‐onset HIT was defined as an abrupt drop in platelet count upon receiving a heparin product, due to heparin exposure within the previous 100 days. Delayed‐onset HIT was defined as HIT that developed several days after discontinuation of heparin. Other evident causes of thrombocytopenia were ruled out.

Statistical Analysis of Retrospective Study of Unintentional Adverse Effects

Regression analysis with chi‐square and ANOVA were used in the analysis of the demographic data. RRs were calculated for the number of cases coded with an anticoagulant‐related adverse event secondary thrombocytopenia before and after the order set implementation.

Educational Efforts and Feedback

Members of the multidisciplinary team presented information on HA VTE and the VTE prevention protocol at Medical and Surgical grand rounds, teaching rounds, and noon conference, averaging 1 educational session per quarter. Feedback and education was provided to physicians and nursing staff when audits revealed that a patient had inadequate prophylaxis with reference to the protocol standard. In addition, these conversations provided on opportunity to explore reasons for nonadherence with the protocol, confusion regarding the VTE RAM, and other barriers to effective prophylaxis, thereby providing guidance for further protocol revision and educational efforts. We adjusted the order set based on active monitoring of order set use and the audit process.

Interobserver Agreement

The VTE RAM interobserver agreement was assessed on 150 patients with 5 observers as described above. The kappa score for the VTE risk level was 0.81. The kappa score for the judgment of whether the patient was on adequate prophylaxis or not was 0.90.

Impact on Percent of Patients with Adequate Prophylaxis (Longitudinal Audits)

Audits of randomly sampled inpatients occurred longitudinally throughout the study period as described above. Based on the intervention, the percent of patients on adequate prophylaxis improved significantly (P < 0.001) by each calendar year (see Table 3), from a baseline of 58% in 2005 to 78% in 2006 (unadjusted relative benefit = 1.35; 95% confidence interval [CI] = 1.28‐1.43), and 93% in 2007 (unadjusted relative benefit = 1.61; 95% CI = 1.52, 1.69). The improvement seen was more marked in the moderate VTE risk patients when compared to the high VTE risk patients. The percent of audited VTE prophylaxis improved from 53% in calendar year (CY) 2005 to 93% in 2007 (unadjusted relative benefit = 1.75; 95% CI = 1.70‐1.81) in the moderate VTE risk group, while the high VTE risk group improved from 83% to 92% in the same time period (unadjusted relative benefit = 1.11; 95% CI = 0.95‐1.25).

Overall, adequate VTE prophylaxis was present in over 98% of audited patients in the last 6 months of 2007, and this high rate has been sustained throughout 2008. Age, ethnicity, and gender were not associated with differential rates of adequate VTE prophylaxis.

Figure 1 is a timeline of interventions and the impact on the prevalence of adequate VTE prophylaxis. The first 7 to 8 months represent the baseline rate 50% to 55% of VTE prophylaxis. In this baseline period, the improvement team was meeting, but had not yet begun meeting with the large variety of medical and surgical service leaders. Consensus‐building sessions with these leaders in the latter part of 2005 through mid‐2006 correlated with improvement in adequate VTE prophylaxis rates to near 70%. The consensus‐building sessions also prepared these varied services for a go live date of the modular order set that was incorporated into all admit and transfer order sets, often replacing preexisting orders referring to VTE prevention measures. The order set resulted in an improvement to 80% adequate prophylaxis, with the incremental improvement occurring virtually overnight with the go live date at the onset of quarter 2 (Q2) of 2006. Monitoring of the order set use confirmed that it was easy and efficient to use, but also revealed that physicians were at times classifying patients as low VTE risk inaccurately, when they possessed qualities that actually qualified them for moderate risk status by our protocol. We therefore inserted a secondary CPOE screen when patients were categorized as low VTE risk, asking the physician to deny or confirm that the patient had no risk factors that qualified them for moderate risk status. This confirmation screen essentially acted as a reminder to the physician to ask Are you sure this patient does not need VTE prophylaxis? This minor modification of the CPOE order set improved adequate VTE prophylaxis rates to 90%. Finally, we asked nurses to evaluate patients who were not on therapeutic or prophylactic doses of anticoagulants. Patients with VTE risk factors but no obvious contraindications generated a note from the nurse to the doctor, prompting the doctor to reassess VTE risk and potential contraindications. This simple intervention raised the percent of audited patients on adequate VTE prophylaxis to 98% in the last 6 months of 2007.

Figure 1

Description of Prospectively Identified VTE

We identified 748 cases of VTE among patients admitted to the medical center over the 36‐month study period; 387 (52%) were community‐acquired VTE. There were 361 HA cases (48% of total cases) over the same time period. There was no difference in age, gender, or BMI between the community‐acquired and hospital‐related VTE.

Of the 361 HA cases, 199 (55%) occurred on Surgical Services and 162 (45%) occurred on Medical Services; 58 (16%) unique patients had pulmonary emboli, while 303 (84%) patients experienced only DVT. Remarkably, almost one‐third of the DVT occurred in the upper extremities (108 upper extremities, 240 lower extremities), and most (80%) of the upper‐extremity DVT were associated with central venous catheters.

Of 361 HA VTE cases, 292 (81%) occurred in those in the moderate VTE risk category, 69 HA VTE cases occurred in high‐risk category patients (19%), and no VTE occurred in patients in the low‐risk category.

Improvement in HA VTE

HA VTE were identified and each case analyzed on an ongoing basis over the entire 3 year study period, as described above. Table 4 depicts a comparison of HA VTE on a year‐to‐year basis and the impact of the VTE prevention protocol on the incidence of HA VTE. In 2007 (the first full CY after the implementation of the order set) there was a 39% relative risk reduction (RRR) in the risk of experiencing an HA VTE. The reduction in the risk of preventable HA VTE was even more marked (RRR = 86%; 7 preventable VTE in 2007, compared to 44 in baseline year of 2005; RR = 0.14; 95% CI = 0.06‐0.31).

Retrospective Analysis of Impact on HIT and Bleeding

There were no statistically significant differences in the number of cases coded for an anticoagulant‐related bleed or secondary thrombocytopenia (Table 5). Chart review revealed there were 2 cases of minor bleeding attributable to pharmacologic VTE prophylaxis before the order set implementation. There were no cases after implementation. No cases of HIT attributable to pharmacologic VTE prophylaxis were identified in either study period, with all cases being attributed to therapeutic anticoagulation.