Adam Wachter, MD

Case

A 65-year-old woman presents to the emergency department with a chief complaint of shortness of breath for 3 days. Medical history is notable for moderate chronic obstructive pulmonary disorder, systolic heart failure with last known ejection fraction (EF) of 35% and type 2 diabetes complicated by hyperglycemia when on steroids. You are talking the case over with colleagues and they suggest point-of-care ultrasound (POCUS) would be useful in her case.
 

Brief overview of the issue

Once mainly used by ED and critical care physicians, POCUS is now a tool that many hospitalists are using at the bedside. POCUS differs from traditional comprehensive ultrasounds in the following ways: POCUS is designed to answer a specific clinical question (as opposed to evaluating all organs in a specific region), POCUS exams are performed by the clinician who is formulating the clinical question (as opposed to by a consultative service such as cardiology and radiology), and POCUS can evaluate multiple organ systems (such as by evaluating a patient’s heart, lungs, and inferior vena cava to determine the etiology of hypoxia).

Hospitalist use of POCUS may include guiding procedures, aiding in diagnosis, and assessing effectiveness of treatment. Many high-quality studies have been published that support the use of POCUS and have proven that POCUS can decrease medical errors, help reach diagnoses in a more expedited fashion, and complement or replace more advanced imaging.

A challenge of POCUS is that it is user dependent and there are no established standards for hospitalists in POCUS training. As the Society of Hospital Medicine position statement on POCUS points out, there is a significant difference between skill levels required to obtain a certificate of completion for POCUS training and a certificate of competency in POCUS. Therefore, it is recommended hospitalists work with local credentialing committees to delineate the requirements for POCUS use.
 

Overview of the data

POCUS for initial assessment and diagnosis of heart failure (HF)

Use of POCUS in cases of suspected HF includes examination of the heart, lungs, and inferior vena cava (IVC). Cardiac ultrasound provides an estimated ejection fraction. Lung ultrasound (LUS) functions to examine for B lines and pleural effusions. The presence of more than three B lines per thoracic zone bilaterally suggests cardiogenic pulmonary edema. Scanning the IVC provides a noninvasive way to assess volume status and is especially helpful when body habitus prevents accurate assessment of jugular venous pressure.

Several studies have addressed the utility of bedside ultrasound in the initial assessment or diagnosis of acute decompensated heart failure (ADHF) in patients presenting with dyspnea in emergency or inpatient settings. Positive B lines are a useful finding, with high sensitivities, high specificities, and positive likelihood ratios. One large multicenter prospective study found LUS to have a sensitivity of 90.5%, specificity of 93.5%, and positive and negative LRs of 14.0 and 0.10, respectively.¹ Another large multicenter prospective cohort study showed that LUS was more sensitive and more specific than chest x-ray (CXR) and brain natriuretic peptide in detecting ADHF.² Additional POCUS findings that have shown relatively high sensitivities and specificities in the initial diagnosis of ADHF include pleural effusion, reduced left ventricular ejection fraction (LVEF), increased left ventricular end-diastolic dimension, and jugular venous distention.

Data also exists on assessments of ADHF using combinations of POCUS findings; for example, lung and cardiac ultrasound (LuCUS) protocols include an evaluation for B lines, assessment of IVC size and collapsibility, and determination of LVEF, although this has mainly been examined in ED patients. For patients who presented to the ED with undifferentiated dyspnea, one such study showed a specificity of 100% when a LuCUS protocol was used to diagnose ADHF while another study showed that the use of a LuCUS protocol changed management in 47% of patients.^3,4 Of note, although each LuCUS protocol integrated the use of lung findings, IVC collapsibility, and LVEF, the exact protocols varied by institution. Finally, it has been established in multiple studies that LUS used in addition to standard workup including history and physical, labs, and electrocardiogram has been shown to increase diagnostic accuracy.^2,5
 

Using POCUS to guide diuretic therapy in HF

To date, there have been multiple small studies published on the utility of daily POCUS in hospitalized patients with ADHF to help assess response to treatment and guide diuresis by looking for reduction in B lines on LUS or a change in IVC size or collapsibility. Volpicelli and colleagues showed that daily LUS was at least as good as daily CXR in monitoring response to therapy.⁶ Similarly, Mozzini and colleagues performed a randomized controlled trial of 120 patients admitted for ADHF who were randomized to a CXR group (who had a CXR performed on admission and discharge) and a LUS group (which was performed at admission, 24 hours, 48 hours, 72 hours, and discharge).⁷ This study found that the LUS group underwent a significantly higher number of diuretic dose adjustments as compared with the CXR group (P < .001) and had a modest improvement in LOS, compared with the CXR group. Specifically, median LOS was 8 days in CXR group (range, 4-17 days) and 7 days in the LUS group (range, 3-10 days; P < .001).

The impact of POCUS on length of stay (LOS) and readmissions

There is increasing data that POCUS can have meaningful impacts on patient-centered outcomes (morbidity, mortality, and readmission) while exposing patients to minimal discomfort, no venipuncture, and no radiation exposure. First, multiple studies looked at whether performing focused cardiac US of the IVC as a marker of volume status could predict readmission in patients hospitalized for ADHF.^8,9 Both of these trials showed that plethoric, noncollapsible IVC at discharge were statistically significant predictors of readmission. In fact, Goonewardena and colleagues demonstrated that patients who required readmission had an enlarged IVC at discharge nearly 3 times more frequently (21% vs. 61%, P < .001) and abnormal IVC collapsibility 1.5 times more frequently (41% vs. 71%, P = .01) as compared with patients who remained out of the hospital.⁹

Similarly, a subsequent trial looked at whether IVC size on admission was of prognostic importance in patients hospitalized for ADHF and showed that admission IVC diameter was an independent predictor of both 90-day mortality (hazard ratio, 5.88; 95% confidence interval, 1.21-28.10; P = .025) and 90-day readmission (HR, 3.20; 95% CI, 1.24-8.21; P = .016).¹⁰ Additionally, LUS heart failure assessment for pulmonary congestion by counting B lines also showed that having more than 15 B lines prior to discharge was an independent predictor of readmission for ADHF at 6 months (HR, 11.74; 95% CI, 1.30-106.16).¹¹

A challenge of POCUS: Obtaining competency

As previously noted, there are not yet any established standards for training and assessing hospitalists in POCUS. The SHM Position Statement on POCUS recommends the following criteria for training⁵: the training environment should be similar to the location in which the trainee will practice, training and feedback should occur in real time, the trainee should be taught specific applications of POCUS (such as cardiac US, LUS, and IVC US) as each application comes with unique skills and knowledge, clinical competence must be achieved and demonstrated, and continued education and feedback are necessary once competence is obtained.¹² SHM recommends residency-based training pathways, training through a local or national program such as the SHM POCUS certificate program, or training through other medical societies for hospitalists already in practice.

Application of the data to our original case

Targeted POCUS using the LuCUS protocol is performed and reveals three B lines in two lung zones bilaterally, moderate bilateral pleural effusions, EF 20%, and a noncollapsible IVC leading to a diagnosis of ADHF. Her ADHF is treated with intravenous diuresis. She is continued on her chronic maintenance chronic obstructive pulmonary disorder regimen but does not receive steroids, avoiding hyperglycemia that has complicated prior admissions. Over the next few days her respiratory and cardiac status is monitored using POCUS to assess her response to therapy and titrate her diuretics to her true dry weight, which was several pounds lower than her previously assumed dry weight. At discharge she is instructed to use the new dry weight which may avoid readmissions for HF.

Bottom line

POCUS improves diagnostic accuracy and facilitates volume assessment and management in acute decompensated heart failure.

Dr. Farber is a medical instructor at Duke University and hospitalist at Duke Regional Hospital, both in Durham, N.C. Dr. Marcantonio is a medical instructor in the department of internal medicine and department of pediatrics at Duke University and hospitalist at Duke University Hospital and Duke Regional Hospital. Dr. Stafford and Dr. Brooks are assistant professors of medicine and hospitalists at Duke Regional Hospital. Dr. Wachter is associate medical director at Duke Regional Hospital and assistant professor at Duke University. Dr. Menon is a hospitalist at Duke University. Dr. Sharma is associate medical director for clinical education at Duke Regional Hospital and associate professor of medicine at Duke University.

References

1. Pivetta E et al. Lung ultrasound integrated with clinical assessment for the diagnosis of acute decompensated heart failure in the emergency department: A randomized controlled trial. Eur J Heart Fail. 2019 Jun;21(6):754-66. doi: 10.1002/ejhf.1379.

2. Pivetta E et al. Lung ultrasound-implemented diagnosis of acute decompensated heart failure in the ED: A SIMEU multicenter study. Chest. 2015;148(1):202-10. doi: 10.1378/chest.14-2608.

3. Anderson KL et al. Diagnosing heart failure among acutely dyspneic patients with cardiac, inferior vena cava, and lung ultrasonography. Am J Emerg Med. 2013;31:1208-14. doi: 10.1016/j.ajem.2013.05.007.

4. Russell FM et al. Diagnosing acute heart failure in patients with undifferentiated dyspnea: A lung and cardiac ultrasound (LuCUS) protocol. Acad Emerg Med. 2015;22(2):182-91. doi:10.1111/acem.12570.

5. Maw AM et al. Diagnostic accuracy of point-of-care lung ultrasonography and chest radiography in adults with symptoms suggestive of acute decompensated heart failure: A systematic review and meta-analysis. JAMA Netw Open. 2019 Mar 1;2(3):e190703. doi:10.1001/jamanetworkopen.2019.0703.

6. Volpicelli G et al. Bedside ultrasound of the lung for the monitoring of acute decompensated heart failure. Am J Emerg Med. 2008 Jun;26(5):585-91. doi:10.1016/j.ajem.2007.09.014.

7. Mozzini C et al. Lung ultrasound in internal medicine efficiently drives the management of patients with heart failure and speeds up the discharge time. Intern Emerg Med. 2018 Jan;13(1):27-33. doi: 10.1007/s11739-017-1738-1.

8. Laffin LJ et al. Focused cardiac ultrasound as a predictor of readmission in acute decompensated heart failure. Int J Cardiovasc Imaging. 2018;34(7):1075-9. doi:10.1007/s10554-018-1317-1.

9. Goonewardena SN et al. Comparison of hand-carried ultrasound assessment of the inferior vena cava and N-terminal pro-brain natriuretic peptide for predicting readmission after hospitalization for acute decompensated heart failure. JACC Cardiovasc Imaging. 2008;1(5):595-601. doi:10.1016/j.jcmg.2008.06.005.

10. Cubo-Romano P et al. Admission inferior vena cava measurements are associated with mortality after hospitalization for acute decompensated heart failure. J Hosp Med. 2016 Nov;11(11):778-84. doi: 10.1002/jhm.2620.

11. Gargani L et al. Persistent pulmonary congestion before discharge predicts rehospitalization in heart failure: A lung ultrasound study. Cardiovasc Ultrasound. 2015 Sep 4;13:40. doi: 10.1186/s12947-015-0033-4.

12. Soni NJ et al. Point-of-care ultrasound for hospitalists: A Position Statement of the Society of Hospital Medicine. J Hosp Med. 2019 Jan 2;14:E1-6. doi: 10.12788/jhm.3079.

Key points

• Studies have found POCUS improves the diagnosis of acute decompensated heart failure in patients presenting with dyspnea.
• Daily evaluation with POCUS has decreased length of stay in acute decompensated heart failure.
• Credentialing requirements for hospitalists to use POCUS for clinical care vary by hospital.

Additional reading

Maw AM and Soni NJ. Annals for hospitalists inpatient notes – why should hospitalists use point-of-care ultrasound? Ann Intern Med. 2018 Apr 17;168(8):HO2-HO3. doi: 10.7326/M18-0367.

Lewiss RE. “The ultrasound looked fine”: Point of care ultrasound and patient safety. AHRQ’s Patient Safety Network. WebM&M: Case Studies. 2018 Jul 1. https://psnet.ahrq.gov/web-mm/ultrasound-looked-fine-point-care-ultrasound-and-patient-safety.

Quiz: Testing your POCUS knowledge

POCUS is increasingly prevalent in hospital medicine, but use varies among different disease processes. Which organ system ultrasound or lab test would be most helpful in the following scenario?

An acutely dyspneic patient with no past medical history presents to the ED. Chest x-ray is equivocal. Of the following, which study best confirms a diagnosis of acute decompensated heart failure?

A. Brain natriuretic peptide

B. Point-of-care cardiac ultrasound

C. Point-of-care lung ultrasound

D. Point-of-care inferior vena cava ultrasound

Answer

C. Point-of-care lung ultrasound

Multiple studies, including three systematic reviews, have shown that point-of-care lung ultrasound has high sensitivity and specificity to evaluate for B lines as a marker for cardiogenic pulmonary edema. Point-of-care ultrasound of ejection fraction and inferior vena cava have not been evaluated by systematic review although one randomized, controlled trial showed that an EF less than 45% had 74% specificity and 77% sensitivity and IVC collapsibility index less than 20% had an 86% specificity and 52% sensitivity for detection of acute decompensated heart failure. This same study showed that the combination of cardiac, lung, and IVC point-of-care ultrasound had 100% specificity for diagnosing acute decompensated heart failure. In the future, health care providers could rely on this multiorgan evaluation with point-of-care ultrasound to confirm a diagnosis of acute decompensated heart failure in a dyspneic patient.

Case

A 65-year-old woman presents to the emergency department with a chief complaint of shortness of breath for 3 days. Medical history is notable for moderate chronic obstructive pulmonary disorder, systolic heart failure with last known ejection fraction (EF) of 35% and type 2 diabetes complicated by hyperglycemia when on steroids. You are talking the case over with colleagues and they suggest point-of-care ultrasound (POCUS) would be useful in her case.
 

Brief overview of the issue

Once mainly used by ED and critical care physicians, POCUS is now a tool that many hospitalists are using at the bedside. POCUS differs from traditional comprehensive ultrasounds in the following ways: POCUS is designed to answer a specific clinical question (as opposed to evaluating all organs in a specific region), POCUS exams are performed by the clinician who is formulating the clinical question (as opposed to by a consultative service such as cardiology and radiology), and POCUS can evaluate multiple organ systems (such as by evaluating a patient’s heart, lungs, and inferior vena cava to determine the etiology of hypoxia).

Hospitalist use of POCUS may include guiding procedures, aiding in diagnosis, and assessing effectiveness of treatment. Many high-quality studies have been published that support the use of POCUS and have proven that POCUS can decrease medical errors, help reach diagnoses in a more expedited fashion, and complement or replace more advanced imaging.

A challenge of POCUS is that it is user dependent and there are no established standards for hospitalists in POCUS training. As the Society of Hospital Medicine position statement on POCUS points out, there is a significant difference between skill levels required to obtain a certificate of completion for POCUS training and a certificate of competency in POCUS. Therefore, it is recommended hospitalists work with local credentialing committees to delineate the requirements for POCUS use.
 

Overview of the data

POCUS for initial assessment and diagnosis of heart failure (HF)

Use of POCUS in cases of suspected HF includes examination of the heart, lungs, and inferior vena cava (IVC). Cardiac ultrasound provides an estimated ejection fraction. Lung ultrasound (LUS) functions to examine for B lines and pleural effusions. The presence of more than three B lines per thoracic zone bilaterally suggests cardiogenic pulmonary edema. Scanning the IVC provides a noninvasive way to assess volume status and is especially helpful when body habitus prevents accurate assessment of jugular venous pressure.

Several studies have addressed the utility of bedside ultrasound in the initial assessment or diagnosis of acute decompensated heart failure (ADHF) in patients presenting with dyspnea in emergency or inpatient settings. Positive B lines are a useful finding, with high sensitivities, high specificities, and positive likelihood ratios. One large multicenter prospective study found LUS to have a sensitivity of 90.5%, specificity of 93.5%, and positive and negative LRs of 14.0 and 0.10, respectively.¹ Another large multicenter prospective cohort study showed that LUS was more sensitive and more specific than chest x-ray (CXR) and brain natriuretic peptide in detecting ADHF.² Additional POCUS findings that have shown relatively high sensitivities and specificities in the initial diagnosis of ADHF include pleural effusion, reduced left ventricular ejection fraction (LVEF), increased left ventricular end-diastolic dimension, and jugular venous distention.

Data also exists on assessments of ADHF using combinations of POCUS findings; for example, lung and cardiac ultrasound (LuCUS) protocols include an evaluation for B lines, assessment of IVC size and collapsibility, and determination of LVEF, although this has mainly been examined in ED patients. For patients who presented to the ED with undifferentiated dyspnea, one such study showed a specificity of 100% when a LuCUS protocol was used to diagnose ADHF while another study showed that the use of a LuCUS protocol changed management in 47% of patients.^3,4 Of note, although each LuCUS protocol integrated the use of lung findings, IVC collapsibility, and LVEF, the exact protocols varied by institution. Finally, it has been established in multiple studies that LUS used in addition to standard workup including history and physical, labs, and electrocardiogram has been shown to increase diagnostic accuracy.^2,5
 

Using POCUS to guide diuretic therapy in HF

To date, there have been multiple small studies published on the utility of daily POCUS in hospitalized patients with ADHF to help assess response to treatment and guide diuresis by looking for reduction in B lines on LUS or a change in IVC size or collapsibility. Volpicelli and colleagues showed that daily LUS was at least as good as daily CXR in monitoring response to therapy.⁶ Similarly, Mozzini and colleagues performed a randomized controlled trial of 120 patients admitted for ADHF who were randomized to a CXR group (who had a CXR performed on admission and discharge) and a LUS group (which was performed at admission, 24 hours, 48 hours, 72 hours, and discharge).⁷ This study found that the LUS group underwent a significantly higher number of diuretic dose adjustments as compared with the CXR group (P < .001) and had a modest improvement in LOS, compared with the CXR group. Specifically, median LOS was 8 days in CXR group (range, 4-17 days) and 7 days in the LUS group (range, 3-10 days; P < .001).

The impact of POCUS on length of stay (LOS) and readmissions

There is increasing data that POCUS can have meaningful impacts on patient-centered outcomes (morbidity, mortality, and readmission) while exposing patients to minimal discomfort, no venipuncture, and no radiation exposure. First, multiple studies looked at whether performing focused cardiac US of the IVC as a marker of volume status could predict readmission in patients hospitalized for ADHF.^8,9 Both of these trials showed that plethoric, noncollapsible IVC at discharge were statistically significant predictors of readmission. In fact, Goonewardena and colleagues demonstrated that patients who required readmission had an enlarged IVC at discharge nearly 3 times more frequently (21% vs. 61%, P < .001) and abnormal IVC collapsibility 1.5 times more frequently (41% vs. 71%, P = .01) as compared with patients who remained out of the hospital.⁹

Similarly, a subsequent trial looked at whether IVC size on admission was of prognostic importance in patients hospitalized for ADHF and showed that admission IVC diameter was an independent predictor of both 90-day mortality (hazard ratio, 5.88; 95% confidence interval, 1.21-28.10; P = .025) and 90-day readmission (HR, 3.20; 95% CI, 1.24-8.21; P = .016).¹⁰ Additionally, LUS heart failure assessment for pulmonary congestion by counting B lines also showed that having more than 15 B lines prior to discharge was an independent predictor of readmission for ADHF at 6 months (HR, 11.74; 95% CI, 1.30-106.16).¹¹

A challenge of POCUS: Obtaining competency

As previously noted, there are not yet any established standards for training and assessing hospitalists in POCUS. The SHM Position Statement on POCUS recommends the following criteria for training⁵: the training environment should be similar to the location in which the trainee will practice, training and feedback should occur in real time, the trainee should be taught specific applications of POCUS (such as cardiac US, LUS, and IVC US) as each application comes with unique skills and knowledge, clinical competence must be achieved and demonstrated, and continued education and feedback are necessary once competence is obtained.¹² SHM recommends residency-based training pathways, training through a local or national program such as the SHM POCUS certificate program, or training through other medical societies for hospitalists already in practice.

Application of the data to our original case

Targeted POCUS using the LuCUS protocol is performed and reveals three B lines in two lung zones bilaterally, moderate bilateral pleural effusions, EF 20%, and a noncollapsible IVC leading to a diagnosis of ADHF. Her ADHF is treated with intravenous diuresis. She is continued on her chronic maintenance chronic obstructive pulmonary disorder regimen but does not receive steroids, avoiding hyperglycemia that has complicated prior admissions. Over the next few days her respiratory and cardiac status is monitored using POCUS to assess her response to therapy and titrate her diuretics to her true dry weight, which was several pounds lower than her previously assumed dry weight. At discharge she is instructed to use the new dry weight which may avoid readmissions for HF.

Bottom line

POCUS improves diagnostic accuracy and facilitates volume assessment and management in acute decompensated heart failure.

Dr. Farber is a medical instructor at Duke University and hospitalist at Duke Regional Hospital, both in Durham, N.C. Dr. Marcantonio is a medical instructor in the department of internal medicine and department of pediatrics at Duke University and hospitalist at Duke University Hospital and Duke Regional Hospital. Dr. Stafford and Dr. Brooks are assistant professors of medicine and hospitalists at Duke Regional Hospital. Dr. Wachter is associate medical director at Duke Regional Hospital and assistant professor at Duke University. Dr. Menon is a hospitalist at Duke University. Dr. Sharma is associate medical director for clinical education at Duke Regional Hospital and associate professor of medicine at Duke University.

References

1. Pivetta E et al. Lung ultrasound integrated with clinical assessment for the diagnosis of acute decompensated heart failure in the emergency department: A randomized controlled trial. Eur J Heart Fail. 2019 Jun;21(6):754-66. doi: 10.1002/ejhf.1379.

2. Pivetta E et al. Lung ultrasound-implemented diagnosis of acute decompensated heart failure in the ED: A SIMEU multicenter study. Chest. 2015;148(1):202-10. doi: 10.1378/chest.14-2608.

3. Anderson KL et al. Diagnosing heart failure among acutely dyspneic patients with cardiac, inferior vena cava, and lung ultrasonography. Am J Emerg Med. 2013;31:1208-14. doi: 10.1016/j.ajem.2013.05.007.

4. Russell FM et al. Diagnosing acute heart failure in patients with undifferentiated dyspnea: A lung and cardiac ultrasound (LuCUS) protocol. Acad Emerg Med. 2015;22(2):182-91. doi:10.1111/acem.12570.

5. Maw AM et al. Diagnostic accuracy of point-of-care lung ultrasonography and chest radiography in adults with symptoms suggestive of acute decompensated heart failure: A systematic review and meta-analysis. JAMA Netw Open. 2019 Mar 1;2(3):e190703. doi:10.1001/jamanetworkopen.2019.0703.

6. Volpicelli G et al. Bedside ultrasound of the lung for the monitoring of acute decompensated heart failure. Am J Emerg Med. 2008 Jun;26(5):585-91. doi:10.1016/j.ajem.2007.09.014.

7. Mozzini C et al. Lung ultrasound in internal medicine efficiently drives the management of patients with heart failure and speeds up the discharge time. Intern Emerg Med. 2018 Jan;13(1):27-33. doi: 10.1007/s11739-017-1738-1.

8. Laffin LJ et al. Focused cardiac ultrasound as a predictor of readmission in acute decompensated heart failure. Int J Cardiovasc Imaging. 2018;34(7):1075-9. doi:10.1007/s10554-018-1317-1.

9. Goonewardena SN et al. Comparison of hand-carried ultrasound assessment of the inferior vena cava and N-terminal pro-brain natriuretic peptide for predicting readmission after hospitalization for acute decompensated heart failure. JACC Cardiovasc Imaging. 2008;1(5):595-601. doi:10.1016/j.jcmg.2008.06.005.

10. Cubo-Romano P et al. Admission inferior vena cava measurements are associated with mortality after hospitalization for acute decompensated heart failure. J Hosp Med. 2016 Nov;11(11):778-84. doi: 10.1002/jhm.2620.

11. Gargani L et al. Persistent pulmonary congestion before discharge predicts rehospitalization in heart failure: A lung ultrasound study. Cardiovasc Ultrasound. 2015 Sep 4;13:40. doi: 10.1186/s12947-015-0033-4.

12. Soni NJ et al. Point-of-care ultrasound for hospitalists: A Position Statement of the Society of Hospital Medicine. J Hosp Med. 2019 Jan 2;14:E1-6. doi: 10.12788/jhm.3079.

Key points

• Studies have found POCUS improves the diagnosis of acute decompensated heart failure in patients presenting with dyspnea.
• Daily evaluation with POCUS has decreased length of stay in acute decompensated heart failure.
• Credentialing requirements for hospitalists to use POCUS for clinical care vary by hospital.

Additional reading

Maw AM and Soni NJ. Annals for hospitalists inpatient notes – why should hospitalists use point-of-care ultrasound? Ann Intern Med. 2018 Apr 17;168(8):HO2-HO3. doi: 10.7326/M18-0367.

Lewiss RE. “The ultrasound looked fine”: Point of care ultrasound and patient safety. AHRQ’s Patient Safety Network. WebM&M: Case Studies. 2018 Jul 1. https://psnet.ahrq.gov/web-mm/ultrasound-looked-fine-point-care-ultrasound-and-patient-safety.

Quiz: Testing your POCUS knowledge

POCUS is increasingly prevalent in hospital medicine, but use varies among different disease processes. Which organ system ultrasound or lab test would be most helpful in the following scenario?

An acutely dyspneic patient with no past medical history presents to the ED. Chest x-ray is equivocal. Of the following, which study best confirms a diagnosis of acute decompensated heart failure?

A. Brain natriuretic peptide

B. Point-of-care cardiac ultrasound

C. Point-of-care lung ultrasound

D. Point-of-care inferior vena cava ultrasound

Answer

C. Point-of-care lung ultrasound

Multiple studies, including three systematic reviews, have shown that point-of-care lung ultrasound has high sensitivity and specificity to evaluate for B lines as a marker for cardiogenic pulmonary edema. Point-of-care ultrasound of ejection fraction and inferior vena cava have not been evaluated by systematic review although one randomized, controlled trial showed that an EF less than 45% had 74% specificity and 77% sensitivity and IVC collapsibility index less than 20% had an 86% specificity and 52% sensitivity for detection of acute decompensated heart failure. This same study showed that the combination of cardiac, lung, and IVC point-of-care ultrasound had 100% specificity for diagnosing acute decompensated heart failure. In the future, health care providers could rely on this multiorgan evaluation with point-of-care ultrasound to confirm a diagnosis of acute decompensated heart failure in a dyspneic patient.

Case

A 65-year-old woman presents to the emergency department with a chief complaint of shortness of breath for 3 days. Medical history is notable for moderate chronic obstructive pulmonary disorder, systolic heart failure with last known ejection fraction (EF) of 35% and type 2 diabetes complicated by hyperglycemia when on steroids. You are talking the case over with colleagues and they suggest point-of-care ultrasound (POCUS) would be useful in her case.
 

Brief overview of the issue

Once mainly used by ED and critical care physicians, POCUS is now a tool that many hospitalists are using at the bedside. POCUS differs from traditional comprehensive ultrasounds in the following ways: POCUS is designed to answer a specific clinical question (as opposed to evaluating all organs in a specific region), POCUS exams are performed by the clinician who is formulating the clinical question (as opposed to by a consultative service such as cardiology and radiology), and POCUS can evaluate multiple organ systems (such as by evaluating a patient’s heart, lungs, and inferior vena cava to determine the etiology of hypoxia).

Hospitalist use of POCUS may include guiding procedures, aiding in diagnosis, and assessing effectiveness of treatment. Many high-quality studies have been published that support the use of POCUS and have proven that POCUS can decrease medical errors, help reach diagnoses in a more expedited fashion, and complement or replace more advanced imaging.

A challenge of POCUS is that it is user dependent and there are no established standards for hospitalists in POCUS training. As the Society of Hospital Medicine position statement on POCUS points out, there is a significant difference between skill levels required to obtain a certificate of completion for POCUS training and a certificate of competency in POCUS. Therefore, it is recommended hospitalists work with local credentialing committees to delineate the requirements for POCUS use.
 

Overview of the data

POCUS for initial assessment and diagnosis of heart failure (HF)

Use of POCUS in cases of suspected HF includes examination of the heart, lungs, and inferior vena cava (IVC). Cardiac ultrasound provides an estimated ejection fraction. Lung ultrasound (LUS) functions to examine for B lines and pleural effusions. The presence of more than three B lines per thoracic zone bilaterally suggests cardiogenic pulmonary edema. Scanning the IVC provides a noninvasive way to assess volume status and is especially helpful when body habitus prevents accurate assessment of jugular venous pressure.

Several studies have addressed the utility of bedside ultrasound in the initial assessment or diagnosis of acute decompensated heart failure (ADHF) in patients presenting with dyspnea in emergency or inpatient settings. Positive B lines are a useful finding, with high sensitivities, high specificities, and positive likelihood ratios. One large multicenter prospective study found LUS to have a sensitivity of 90.5%, specificity of 93.5%, and positive and negative LRs of 14.0 and 0.10, respectively.¹ Another large multicenter prospective cohort study showed that LUS was more sensitive and more specific than chest x-ray (CXR) and brain natriuretic peptide in detecting ADHF.² Additional POCUS findings that have shown relatively high sensitivities and specificities in the initial diagnosis of ADHF include pleural effusion, reduced left ventricular ejection fraction (LVEF), increased left ventricular end-diastolic dimension, and jugular venous distention.

Data also exists on assessments of ADHF using combinations of POCUS findings; for example, lung and cardiac ultrasound (LuCUS) protocols include an evaluation for B lines, assessment of IVC size and collapsibility, and determination of LVEF, although this has mainly been examined in ED patients. For patients who presented to the ED with undifferentiated dyspnea, one such study showed a specificity of 100% when a LuCUS protocol was used to diagnose ADHF while another study showed that the use of a LuCUS protocol changed management in 47% of patients.^3,4 Of note, although each LuCUS protocol integrated the use of lung findings, IVC collapsibility, and LVEF, the exact protocols varied by institution. Finally, it has been established in multiple studies that LUS used in addition to standard workup including history and physical, labs, and electrocardiogram has been shown to increase diagnostic accuracy.^2,5
 

Using POCUS to guide diuretic therapy in HF

To date, there have been multiple small studies published on the utility of daily POCUS in hospitalized patients with ADHF to help assess response to treatment and guide diuresis by looking for reduction in B lines on LUS or a change in IVC size or collapsibility. Volpicelli and colleagues showed that daily LUS was at least as good as daily CXR in monitoring response to therapy.⁶ Similarly, Mozzini and colleagues performed a randomized controlled trial of 120 patients admitted for ADHF who were randomized to a CXR group (who had a CXR performed on admission and discharge) and a LUS group (which was performed at admission, 24 hours, 48 hours, 72 hours, and discharge).⁷ This study found that the LUS group underwent a significantly higher number of diuretic dose adjustments as compared with the CXR group (P < .001) and had a modest improvement in LOS, compared with the CXR group. Specifically, median LOS was 8 days in CXR group (range, 4-17 days) and 7 days in the LUS group (range, 3-10 days; P < .001).

The impact of POCUS on length of stay (LOS) and readmissions

There is increasing data that POCUS can have meaningful impacts on patient-centered outcomes (morbidity, mortality, and readmission) while exposing patients to minimal discomfort, no venipuncture, and no radiation exposure. First, multiple studies looked at whether performing focused cardiac US of the IVC as a marker of volume status could predict readmission in patients hospitalized for ADHF.^8,9 Both of these trials showed that plethoric, noncollapsible IVC at discharge were statistically significant predictors of readmission. In fact, Goonewardena and colleagues demonstrated that patients who required readmission had an enlarged IVC at discharge nearly 3 times more frequently (21% vs. 61%, P < .001) and abnormal IVC collapsibility 1.5 times more frequently (41% vs. 71%, P = .01) as compared with patients who remained out of the hospital.⁹

Similarly, a subsequent trial looked at whether IVC size on admission was of prognostic importance in patients hospitalized for ADHF and showed that admission IVC diameter was an independent predictor of both 90-day mortality (hazard ratio, 5.88; 95% confidence interval, 1.21-28.10; P = .025) and 90-day readmission (HR, 3.20; 95% CI, 1.24-8.21; P = .016).¹⁰ Additionally, LUS heart failure assessment for pulmonary congestion by counting B lines also showed that having more than 15 B lines prior to discharge was an independent predictor of readmission for ADHF at 6 months (HR, 11.74; 95% CI, 1.30-106.16).¹¹

A challenge of POCUS: Obtaining competency

As previously noted, there are not yet any established standards for training and assessing hospitalists in POCUS. The SHM Position Statement on POCUS recommends the following criteria for training⁵: the training environment should be similar to the location in which the trainee will practice, training and feedback should occur in real time, the trainee should be taught specific applications of POCUS (such as cardiac US, LUS, and IVC US) as each application comes with unique skills and knowledge, clinical competence must be achieved and demonstrated, and continued education and feedback are necessary once competence is obtained.¹² SHM recommends residency-based training pathways, training through a local or national program such as the SHM POCUS certificate program, or training through other medical societies for hospitalists already in practice.

Application of the data to our original case

Targeted POCUS using the LuCUS protocol is performed and reveals three B lines in two lung zones bilaterally, moderate bilateral pleural effusions, EF 20%, and a noncollapsible IVC leading to a diagnosis of ADHF. Her ADHF is treated with intravenous diuresis. She is continued on her chronic maintenance chronic obstructive pulmonary disorder regimen but does not receive steroids, avoiding hyperglycemia that has complicated prior admissions. Over the next few days her respiratory and cardiac status is monitored using POCUS to assess her response to therapy and titrate her diuretics to her true dry weight, which was several pounds lower than her previously assumed dry weight. At discharge she is instructed to use the new dry weight which may avoid readmissions for HF.

Bottom line

POCUS improves diagnostic accuracy and facilitates volume assessment and management in acute decompensated heart failure.

Dr. Farber is a medical instructor at Duke University and hospitalist at Duke Regional Hospital, both in Durham, N.C. Dr. Marcantonio is a medical instructor in the department of internal medicine and department of pediatrics at Duke University and hospitalist at Duke University Hospital and Duke Regional Hospital. Dr. Stafford and Dr. Brooks are assistant professors of medicine and hospitalists at Duke Regional Hospital. Dr. Wachter is associate medical director at Duke Regional Hospital and assistant professor at Duke University. Dr. Menon is a hospitalist at Duke University. Dr. Sharma is associate medical director for clinical education at Duke Regional Hospital and associate professor of medicine at Duke University.

References

1. Pivetta E et al. Lung ultrasound integrated with clinical assessment for the diagnosis of acute decompensated heart failure in the emergency department: A randomized controlled trial. Eur J Heart Fail. 2019 Jun;21(6):754-66. doi: 10.1002/ejhf.1379.

2. Pivetta E et al. Lung ultrasound-implemented diagnosis of acute decompensated heart failure in the ED: A SIMEU multicenter study. Chest. 2015;148(1):202-10. doi: 10.1378/chest.14-2608.

3. Anderson KL et al. Diagnosing heart failure among acutely dyspneic patients with cardiac, inferior vena cava, and lung ultrasonography. Am J Emerg Med. 2013;31:1208-14. doi: 10.1016/j.ajem.2013.05.007.

4. Russell FM et al. Diagnosing acute heart failure in patients with undifferentiated dyspnea: A lung and cardiac ultrasound (LuCUS) protocol. Acad Emerg Med. 2015;22(2):182-91. doi:10.1111/acem.12570.

5. Maw AM et al. Diagnostic accuracy of point-of-care lung ultrasonography and chest radiography in adults with symptoms suggestive of acute decompensated heart failure: A systematic review and meta-analysis. JAMA Netw Open. 2019 Mar 1;2(3):e190703. doi:10.1001/jamanetworkopen.2019.0703.

6. Volpicelli G et al. Bedside ultrasound of the lung for the monitoring of acute decompensated heart failure. Am J Emerg Med. 2008 Jun;26(5):585-91. doi:10.1016/j.ajem.2007.09.014.

7. Mozzini C et al. Lung ultrasound in internal medicine efficiently drives the management of patients with heart failure and speeds up the discharge time. Intern Emerg Med. 2018 Jan;13(1):27-33. doi: 10.1007/s11739-017-1738-1.

8. Laffin LJ et al. Focused cardiac ultrasound as a predictor of readmission in acute decompensated heart failure. Int J Cardiovasc Imaging. 2018;34(7):1075-9. doi:10.1007/s10554-018-1317-1.

9. Goonewardena SN et al. Comparison of hand-carried ultrasound assessment of the inferior vena cava and N-terminal pro-brain natriuretic peptide for predicting readmission after hospitalization for acute decompensated heart failure. JACC Cardiovasc Imaging. 2008;1(5):595-601. doi:10.1016/j.jcmg.2008.06.005.

10. Cubo-Romano P et al. Admission inferior vena cava measurements are associated with mortality after hospitalization for acute decompensated heart failure. J Hosp Med. 2016 Nov;11(11):778-84. doi: 10.1002/jhm.2620.

11. Gargani L et al. Persistent pulmonary congestion before discharge predicts rehospitalization in heart failure: A lung ultrasound study. Cardiovasc Ultrasound. 2015 Sep 4;13:40. doi: 10.1186/s12947-015-0033-4.

12. Soni NJ et al. Point-of-care ultrasound for hospitalists: A Position Statement of the Society of Hospital Medicine. J Hosp Med. 2019 Jan 2;14:E1-6. doi: 10.12788/jhm.3079.

Key points

• Studies have found POCUS improves the diagnosis of acute decompensated heart failure in patients presenting with dyspnea.
• Daily evaluation with POCUS has decreased length of stay in acute decompensated heart failure.
• Credentialing requirements for hospitalists to use POCUS for clinical care vary by hospital.

Additional reading

Maw AM and Soni NJ. Annals for hospitalists inpatient notes – why should hospitalists use point-of-care ultrasound? Ann Intern Med. 2018 Apr 17;168(8):HO2-HO3. doi: 10.7326/M18-0367.

Lewiss RE. “The ultrasound looked fine”: Point of care ultrasound and patient safety. AHRQ’s Patient Safety Network. WebM&M: Case Studies. 2018 Jul 1. https://psnet.ahrq.gov/web-mm/ultrasound-looked-fine-point-care-ultrasound-and-patient-safety.

Quiz: Testing your POCUS knowledge

POCUS is increasingly prevalent in hospital medicine, but use varies among different disease processes. Which organ system ultrasound or lab test would be most helpful in the following scenario?

An acutely dyspneic patient with no past medical history presents to the ED. Chest x-ray is equivocal. Of the following, which study best confirms a diagnosis of acute decompensated heart failure?

A. Brain natriuretic peptide

B. Point-of-care cardiac ultrasound

C. Point-of-care lung ultrasound

D. Point-of-care inferior vena cava ultrasound

Answer

C. Point-of-care lung ultrasound

Multiple studies, including three systematic reviews, have shown that point-of-care lung ultrasound has high sensitivity and specificity to evaluate for B lines as a marker for cardiogenic pulmonary edema. Point-of-care ultrasound of ejection fraction and inferior vena cava have not been evaluated by systematic review although one randomized, controlled trial showed that an EF less than 45% had 74% specificity and 77% sensitivity and IVC collapsibility index less than 20% had an 86% specificity and 52% sensitivity for detection of acute decompensated heart failure. This same study showed that the combination of cardiac, lung, and IVC point-of-care ultrasound had 100% specificity for diagnosing acute decompensated heart failure. In the future, health care providers could rely on this multiorgan evaluation with point-of-care ultrasound to confirm a diagnosis of acute decompensated heart failure in a dyspneic patient.

Background: Current guidelines recommend against using aspirin in combination with warfarin for patients with AFib, unless the patient has another indication for aspirin such as recent percutaneous coronary intervention (PCI) or a mechanical heart valve. These recommendations are based on limited clinical trial data that showed an increased risk of adverse events with combination therapy without clinical benefit. Despite these recommendations, recent studies have shown that aspirin use without a clinical indication remains common in patients taking warfarin for AFib. The prevalence of aspirin use without a clinical indication in patients taking warfarin for VTE is less well studied.

Dr. Wachter is an associate medical director at Duke Regional Hospital and an assistant professor of medicine at Duke University.

Background: Current guidelines recommend against using aspirin in combination with warfarin for patients with AFib, unless the patient has another indication for aspirin such as recent percutaneous coronary intervention (PCI) or a mechanical heart valve. These recommendations are based on limited clinical trial data that showed an increased risk of adverse events with combination therapy without clinical benefit. Despite these recommendations, recent studies have shown that aspirin use without a clinical indication remains common in patients taking warfarin for AFib. The prevalence of aspirin use without a clinical indication in patients taking warfarin for VTE is less well studied.

Dr. Wachter is an associate medical director at Duke Regional Hospital and an assistant professor of medicine at Duke University.

Background: Current guidelines recommend against using aspirin in combination with warfarin for patients with AFib, unless the patient has another indication for aspirin such as recent percutaneous coronary intervention (PCI) or a mechanical heart valve. These recommendations are based on limited clinical trial data that showed an increased risk of adverse events with combination therapy without clinical benefit. Despite these recommendations, recent studies have shown that aspirin use without a clinical indication remains common in patients taking warfarin for AFib. The prevalence of aspirin use without a clinical indication in patients taking warfarin for VTE is less well studied.

Dr. Wachter is an associate medical director at Duke Regional Hospital and an assistant professor of medicine at Duke University.

Case

A 78-year-old woman with end-stage renal disease (ESRD) is hospitalized with cellulitis and is incidentally found to be in atrial fibrillation. She does not have a history of mitral stenosis, nor does she have a prosthetic valve. She does have a history of hypertension, diabetes, and prior stroke without residual deficits.

After counseling her about the risk of stroke associated with atrial fibrillation (AFib) she makes it clear she is interested in pharmacologic therapy to minimize her risk of stroke and asks what medication you would recommend for anticoagulation.

Brief overview of the issue

Anticoagulation for AFib is indicated for stroke prophylaxis in patients with an elevated risk of stroke. The CHA₂DS₂-VASc score is useful in calculating an individual patient’s risk of stroke and as a decision tool to determine who would benefit from anticoagulation, and it is recommended in the American Heart Association guidelines.¹

Low-risk patients (CHA₂DS₂-VASc score of 0 in men or 1 in women) should not be started on anticoagulation for stroke prophylaxis. For anyone with a risk factor, other than being female, anticoagulation is indicated and should be considered.

The guideline recommends anticoagulant therapy, not antiplatelet agents. For most of the recent past, this has meant a vitamin K antagonist (warfarin) or sometimes a low-molecular-weight heparin injected subcutaneously. Over the past decade, however, with the approval of multiple direct oral anticoagulants (DOACs), nonwarfarin oral anticoagulation has grown in popularity as the prophylactic medication of choice.²

While the data for patients with preserved renal function is robust, there is far less data to guide decision making for patients with end-stage renal disease.

Overview of the data

Until the introduction of DOACs, warfarin was the main agent used for stroke prophylaxis in patients with end-stage kidney disease and AFib. Professional guidelines favored warfarin for these patients who were mostly excluded from DOAC trials. Specialized conferences also looked at this issue.

The Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference, which reviewed chronic kidney disease and arrhythmias, noted that there were no randomized controlled trials that examined the efficacy and safety of anticoagulation in chronic kidney disease patients with estimated creatinine clearance less than 30 mL/min. They remarked that there was insufficient high-quality evidence to recommend warfarin for the prevention of stroke in patients with AFib and dialysis-dependent chronic kidney disease.

Since, according to other trials, DOACs had better safety profiles in other populations, the conference noted that lower-dose apixaban (2.5 mg orally twice daily) or rivaroxaban (15 mg daily) may be considered in this population until clinical safety data were available. Furthermore, the conference recommended that these patients be treated with a multidisciplinary approach in regards to anticoagulation and have an annual reevaluation of treatment goals, along with a risk-benefit assessment.³

Since the publication of the 2018 AHA guidelines and the guidance document that resulted from the KDIGO conference, additional research has been published comparing anticoagulation with a DOAC versus warfarin for AFib in patients with ESRD.

“Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the United States” was an observational, retrospective, cohort study that compared outcomes in dialysis patients who took warfarin for AFib with those who took apixaban.⁴ Patients’ data was taken from the U.S. Renal Data System database and were included in the final analysis if they had ESRD, a recent diagnosis of AFib or atrial flutter, and a new prescription for either warfarin or apixaban. Outcome measures were stroke or systemic embolism, major bleeding (critical site, transfusion, or death), gastrointestinal bleeding, intracranial bleeding, or death. Drug usage and compliance were assessed using Medicare Part D prescription information.

A total of 25,523 patients met the inclusion/exclusion criteria and had taken either warfarin (n = 23,172) or apixaban (n = 2,351). To account for selection bias in these cohorts, a subset of the warfarin patients was selected based on prognostic score matching. The prognostic score was calculated from the baseline characteristics (which included age, stroke history, diabetes, smoking, antiplatelet medication, liver disease, prior bleeding, and CHA₂DS₂-VASc score). Kaplan-Meier and Cox regression analysis were used to give hazard ratios and 95% confidence intervals for each outcome measure. Prespecified subgroup analyses were conducted to compare apixaban doses, where 44% were prescribed 5 mg b.i.d. and 56% were prescribed 2.5 mg b.i.d..

In the study, patients in the apixaban group had a significantly lower risk of major bleeding as compared with the warfarin group (HR, 0.72; 95% CI, 0.59-0.87; P less than .001) with overall high rates of major bleeding in both groups at 19.7 and 22.9 per 100 patient-years in the apixaban group and warfarin group, respectively. There was no difference in the rate of stroke/systemic embolism between patients receiving apixaban and warfarin (HR, 0.88; 95% CI, 0.69-1.12; P = .29). There was a nonsignificant trend toward decreased risk of GI bleeding in the apixaban group and no significant differences between the groups in the rates of intracranial bleeding. Apixaban was also associated with a nonsignificant trend toward lower risk of mortality (HR, 0.85; 95% CI, 0.71-1.01; P = .06).

Notably, censoring rates because of expired prescriptions or a 1-month gap between prescriptions were high in both groups and the majority of censoring occurred within the first 12 months. Additionally, in dose specific analyses, patients receiving the 5-mg, twice-daily dose were found to have statistically significant decreases in risk of stroke/systemic embolism (P = .035) and mortality (P = .005) as compared with the 2.5-mg, twice-daily dose without significant differences in GI or intracranial bleeding.

There are three ongoing, open-label, randomized, controlled trials examining anticoagulation for nonvalvular AFib in patients with ESRD on hemodialysis with two comparing apixaban to warfarin (or derivative) and the other warfarin versus no anticoagulation.⁵ All trials are in adult patients with documented AFib and CHA₂DS₂-VASc score of at least 2. AKADIA (Germany based) plans to enroll 222 patients and compares a vitamin K antagonist (INR goal, 2-3) with 2.5-mg b.i.d. apixaban patients with ESRD on hemodialysis for at least 3 months with primary outcome of major and clinically relevant nonmajor bleeding and secondary outcome of thromboembolic events, as well as apixaban levels pre- and post hemodialysis.

RENAL-AF (U.S. based) plans to enrolled 762 patients and compares 5-mg b.i.d. apixaban (with 2.5 mg for selected patients) with warfarin in people of chronic hemodialysis with primary outcome of days to first major or clinically relevant nonmajor bleeding event and secondary outcome of stroke, systemic embolism, mortality, adherence and plasma apixaban levels. AVKDIAL (France based) plans to enroll 855 patients and compares no anticoagulation with vitamin K antagonists in patients on hemodialysis for at least 1 month, with primary outcome of cumulative incidence of severe bleeding and thrombosis.

Application of the data to our original case

Our patient is Medicare age with ESRD and newly diagnosed nonvalvular AFib. Recent data suggests apixaban could be used for stroke prevention instead of the prior standard of care, warfarin. This approach is supported in the 2019 guidelines.¹

Patients with ESRD have an increased risk of bleeding and apixaban was shown to have less bleeding complications than warfarin in this analysis. However, only standard-dose apixaban was associated with a statistically significant lower risk of stroke/systemic embolism, major bleeding, and death. Reduced-dose apixaban had a lower risk of major bleeding but no difference for stroke/systemic embolism or death. Reduced-dose apixaban is used for patients who have two out of the following three criteria: aged at least 80 years, weight of at least 60 kg, and creatinine of at least 1.5 mg/dL. Therefore, many Medicare-age patients with ESRD would not be indicated for the dose of apixaban that was shown to improve the most important outcomes of stroke/SE and death.

It may still be beneficial to use apixaban in this patient since it appears to work as well as warfarin for stroke/systemic embolism prevention with less bleeding complications.

Bottom line

For patients who have decided to pursue an anticoagulation strategy for stroke prevention in AFib and have end-stage renal disease, either warfarin or apixaban are sensible options.

Dr. Farber is a medical instructor at Duke University Health System in Durham, N.C. Dr. Stafford is a medical instructor at Duke University. Dr. Sata is assistant professor of medicine at Duke University. Dr. Abdo and Dr. Menon are hospitalists at Duke University. Dr. Brooks is assistant professor of medicine at Duke University. Dr. Wachter is associate medical director at Duke Regional Hospital and assistant professor of medicine at Duke University. Dr. Sharma is associate medical director for clinical education in hospital medicine at Duke Regional Hospital and assistant professor of medicine at Duke University.

References

1. January CT et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2019;139. doi: 1161/CIR.0000000000000665.

2. Lippi G et al. Direct oral anticoagulants: Analysis of worldwide use and popularity using Google Trends. Ann Transl Med. 2017 Aug; 5(16):322. doi: 10.21037/atm.2017.06.65.

3. Turakhia MP et al. Chronic kidney disease and arrhythmias: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Eur Heart J. 2018 Jun 21;39(24):2314-25. doi: 10.1093/eurheartj/ehy060.

4. Siontis KC et al. Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the United States. Circulation. 2018 Oct 9;138(15):1519-29. doi: 10.1161/CIRCULATIONAHA.118.035418.

5. Nigwekar SU et al. Long-term anticoagulation for patient receiving dialysis: Tilting the benefit-to-risk ratio? Circulation. 2018 Oct 9;138(15):1530-3. doi: 10.1161/CIRCULATIONAHA.118.037091.

Key points

• According to 2019 American Heart Association guidelines, warfarin or apixaban are reasonable options for stroke prevention for patients who have end-stage renal disease and who plan for anticoagulation because of atrial fibrillation.
• Recent observational data suggests that apixaban may be safer than warfarin in this population.
• Several randomized, controlled trials are ongoing that may help determine the optimal agent to use in this setting.
• Until more definitive data is available, a reasonable approach is to discuss the risks and benefits of various treatment strategies with patients, and engage a multidisciplinary team (cardiologist, nephrologist, primary care provider, pharmacist) in the decision making process.

Additional reading

January CT et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2019;139. doi: 1161/CIR.0000000000000665.

Nigwekar SU et al. Long-term anticoagulation for patient receiving dialysis: Tilting the benefit to risk ratio? Circulation. 2018 Oct 9;138(15):1530-3. doi: 10.1161/CIRCULATIONAHA.118.037091.

Garlo KG et al. Demystifying the benefits and harms of anticoagulation for atrial fibrillation in chronic kidney disease. Clin J Am Soc Nephrol 2019;14:125-36. doi: 10.2215/CJN.06430518.

Quiz

Two days ago you admitted a 72-year-old woman with end-stage renal disease on dialysis who had developed new-onset atrial fibrillation causing a mild acute diastolic congestive heart failure exacerbation. Transthoracic ECG showed a preserved left ventricular ejection fraction and no significant valvular disease. After two sessions of dialysis in the hospital and initiation of a beta-blocker for control of her heart rate, she is stable and ready for discharge. Her discharge weight is 75 kg.

Which of the following recommendations should you make to this patient regarding anticoagulation for prevention of stroke and systemic embolism from atrial fibrillation?

A. Take warfarin with a international normalized ratio goal of 2.5.

B. Take apixaban 2.5 mg twice a day.

C. Take apixaban 5 mg twice a day.

D. Discuss the risks/benefits of various treatment approaches with the patient, and involve the hospital pharmacist as well as the patient’s nephrologist, cardiologist, and/or primary care provider in the decision making process to reach a consensus and to ensure a safe follow-up plan.

The best answer is D. While A, B, and C are all reasonable approaches based on the available data and current guidelines, the best approach is to involve the patient and the multidisciplinary team in the decision making process. When more clinical trial data becomes available in the future, the optimal approach to managing patients such as this one may become clearer, but until then it makes sense to take into account individual patient characteristics and patient preferences.

Case

A 78-year-old woman with end-stage renal disease (ESRD) is hospitalized with cellulitis and is incidentally found to be in atrial fibrillation. She does not have a history of mitral stenosis, nor does she have a prosthetic valve. She does have a history of hypertension, diabetes, and prior stroke without residual deficits.

After counseling her about the risk of stroke associated with atrial fibrillation (AFib) she makes it clear she is interested in pharmacologic therapy to minimize her risk of stroke and asks what medication you would recommend for anticoagulation.

Brief overview of the issue

Anticoagulation for AFib is indicated for stroke prophylaxis in patients with an elevated risk of stroke. The CHA₂DS₂-VASc score is useful in calculating an individual patient’s risk of stroke and as a decision tool to determine who would benefit from anticoagulation, and it is recommended in the American Heart Association guidelines.¹

Low-risk patients (CHA₂DS₂-VASc score of 0 in men or 1 in women) should not be started on anticoagulation for stroke prophylaxis. For anyone with a risk factor, other than being female, anticoagulation is indicated and should be considered.

The guideline recommends anticoagulant therapy, not antiplatelet agents. For most of the recent past, this has meant a vitamin K antagonist (warfarin) or sometimes a low-molecular-weight heparin injected subcutaneously. Over the past decade, however, with the approval of multiple direct oral anticoagulants (DOACs), nonwarfarin oral anticoagulation has grown in popularity as the prophylactic medication of choice.²

While the data for patients with preserved renal function is robust, there is far less data to guide decision making for patients with end-stage renal disease.

Overview of the data

Until the introduction of DOACs, warfarin was the main agent used for stroke prophylaxis in patients with end-stage kidney disease and AFib. Professional guidelines favored warfarin for these patients who were mostly excluded from DOAC trials. Specialized conferences also looked at this issue.

The Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference, which reviewed chronic kidney disease and arrhythmias, noted that there were no randomized controlled trials that examined the efficacy and safety of anticoagulation in chronic kidney disease patients with estimated creatinine clearance less than 30 mL/min. They remarked that there was insufficient high-quality evidence to recommend warfarin for the prevention of stroke in patients with AFib and dialysis-dependent chronic kidney disease.

Since, according to other trials, DOACs had better safety profiles in other populations, the conference noted that lower-dose apixaban (2.5 mg orally twice daily) or rivaroxaban (15 mg daily) may be considered in this population until clinical safety data were available. Furthermore, the conference recommended that these patients be treated with a multidisciplinary approach in regards to anticoagulation and have an annual reevaluation of treatment goals, along with a risk-benefit assessment.³

Since the publication of the 2018 AHA guidelines and the guidance document that resulted from the KDIGO conference, additional research has been published comparing anticoagulation with a DOAC versus warfarin for AFib in patients with ESRD.

“Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the United States” was an observational, retrospective, cohort study that compared outcomes in dialysis patients who took warfarin for AFib with those who took apixaban.⁴ Patients’ data was taken from the U.S. Renal Data System database and were included in the final analysis if they had ESRD, a recent diagnosis of AFib or atrial flutter, and a new prescription for either warfarin or apixaban. Outcome measures were stroke or systemic embolism, major bleeding (critical site, transfusion, or death), gastrointestinal bleeding, intracranial bleeding, or death. Drug usage and compliance were assessed using Medicare Part D prescription information.

A total of 25,523 patients met the inclusion/exclusion criteria and had taken either warfarin (n = 23,172) or apixaban (n = 2,351). To account for selection bias in these cohorts, a subset of the warfarin patients was selected based on prognostic score matching. The prognostic score was calculated from the baseline characteristics (which included age, stroke history, diabetes, smoking, antiplatelet medication, liver disease, prior bleeding, and CHA₂DS₂-VASc score). Kaplan-Meier and Cox regression analysis were used to give hazard ratios and 95% confidence intervals for each outcome measure. Prespecified subgroup analyses were conducted to compare apixaban doses, where 44% were prescribed 5 mg b.i.d. and 56% were prescribed 2.5 mg b.i.d..

In the study, patients in the apixaban group had a significantly lower risk of major bleeding as compared with the warfarin group (HR, 0.72; 95% CI, 0.59-0.87; P less than .001) with overall high rates of major bleeding in both groups at 19.7 and 22.9 per 100 patient-years in the apixaban group and warfarin group, respectively. There was no difference in the rate of stroke/systemic embolism between patients receiving apixaban and warfarin (HR, 0.88; 95% CI, 0.69-1.12; P = .29). There was a nonsignificant trend toward decreased risk of GI bleeding in the apixaban group and no significant differences between the groups in the rates of intracranial bleeding. Apixaban was also associated with a nonsignificant trend toward lower risk of mortality (HR, 0.85; 95% CI, 0.71-1.01; P = .06).

Notably, censoring rates because of expired prescriptions or a 1-month gap between prescriptions were high in both groups and the majority of censoring occurred within the first 12 months. Additionally, in dose specific analyses, patients receiving the 5-mg, twice-daily dose were found to have statistically significant decreases in risk of stroke/systemic embolism (P = .035) and mortality (P = .005) as compared with the 2.5-mg, twice-daily dose without significant differences in GI or intracranial bleeding.

There are three ongoing, open-label, randomized, controlled trials examining anticoagulation for nonvalvular AFib in patients with ESRD on hemodialysis with two comparing apixaban to warfarin (or derivative) and the other warfarin versus no anticoagulation.⁵ All trials are in adult patients with documented AFib and CHA₂DS₂-VASc score of at least 2. AKADIA (Germany based) plans to enroll 222 patients and compares a vitamin K antagonist (INR goal, 2-3) with 2.5-mg b.i.d. apixaban patients with ESRD on hemodialysis for at least 3 months with primary outcome of major and clinically relevant nonmajor bleeding and secondary outcome of thromboembolic events, as well as apixaban levels pre- and post hemodialysis.

RENAL-AF (U.S. based) plans to enrolled 762 patients and compares 5-mg b.i.d. apixaban (with 2.5 mg for selected patients) with warfarin in people of chronic hemodialysis with primary outcome of days to first major or clinically relevant nonmajor bleeding event and secondary outcome of stroke, systemic embolism, mortality, adherence and plasma apixaban levels. AVKDIAL (France based) plans to enroll 855 patients and compares no anticoagulation with vitamin K antagonists in patients on hemodialysis for at least 1 month, with primary outcome of cumulative incidence of severe bleeding and thrombosis.

Application of the data to our original case

Our patient is Medicare age with ESRD and newly diagnosed nonvalvular AFib. Recent data suggests apixaban could be used for stroke prevention instead of the prior standard of care, warfarin. This approach is supported in the 2019 guidelines.¹

Patients with ESRD have an increased risk of bleeding and apixaban was shown to have less bleeding complications than warfarin in this analysis. However, only standard-dose apixaban was associated with a statistically significant lower risk of stroke/systemic embolism, major bleeding, and death. Reduced-dose apixaban had a lower risk of major bleeding but no difference for stroke/systemic embolism or death. Reduced-dose apixaban is used for patients who have two out of the following three criteria: aged at least 80 years, weight of at least 60 kg, and creatinine of at least 1.5 mg/dL. Therefore, many Medicare-age patients with ESRD would not be indicated for the dose of apixaban that was shown to improve the most important outcomes of stroke/SE and death.

It may still be beneficial to use apixaban in this patient since it appears to work as well as warfarin for stroke/systemic embolism prevention with less bleeding complications.

Bottom line

For patients who have decided to pursue an anticoagulation strategy for stroke prevention in AFib and have end-stage renal disease, either warfarin or apixaban are sensible options.

Dr. Farber is a medical instructor at Duke University Health System in Durham, N.C. Dr. Stafford is a medical instructor at Duke University. Dr. Sata is assistant professor of medicine at Duke University. Dr. Abdo and Dr. Menon are hospitalists at Duke University. Dr. Brooks is assistant professor of medicine at Duke University. Dr. Wachter is associate medical director at Duke Regional Hospital and assistant professor of medicine at Duke University. Dr. Sharma is associate medical director for clinical education in hospital medicine at Duke Regional Hospital and assistant professor of medicine at Duke University.

References

1. January CT et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2019;139. doi: 1161/CIR.0000000000000665.

2. Lippi G et al. Direct oral anticoagulants: Analysis of worldwide use and popularity using Google Trends. Ann Transl Med. 2017 Aug; 5(16):322. doi: 10.21037/atm.2017.06.65.

3. Turakhia MP et al. Chronic kidney disease and arrhythmias: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Eur Heart J. 2018 Jun 21;39(24):2314-25. doi: 10.1093/eurheartj/ehy060.

4. Siontis KC et al. Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the United States. Circulation. 2018 Oct 9;138(15):1519-29. doi: 10.1161/CIRCULATIONAHA.118.035418.

5. Nigwekar SU et al. Long-term anticoagulation for patient receiving dialysis: Tilting the benefit-to-risk ratio? Circulation. 2018 Oct 9;138(15):1530-3. doi: 10.1161/CIRCULATIONAHA.118.037091.

Key points

• According to 2019 American Heart Association guidelines, warfarin or apixaban are reasonable options for stroke prevention for patients who have end-stage renal disease and who plan for anticoagulation because of atrial fibrillation.
• Recent observational data suggests that apixaban may be safer than warfarin in this population.
• Several randomized, controlled trials are ongoing that may help determine the optimal agent to use in this setting.
• Until more definitive data is available, a reasonable approach is to discuss the risks and benefits of various treatment strategies with patients, and engage a multidisciplinary team (cardiologist, nephrologist, primary care provider, pharmacist) in the decision making process.

Additional reading

January CT et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2019;139. doi: 1161/CIR.0000000000000665.

Nigwekar SU et al. Long-term anticoagulation for patient receiving dialysis: Tilting the benefit to risk ratio? Circulation. 2018 Oct 9;138(15):1530-3. doi: 10.1161/CIRCULATIONAHA.118.037091.

Garlo KG et al. Demystifying the benefits and harms of anticoagulation for atrial fibrillation in chronic kidney disease. Clin J Am Soc Nephrol 2019;14:125-36. doi: 10.2215/CJN.06430518.

Quiz

Two days ago you admitted a 72-year-old woman with end-stage renal disease on dialysis who had developed new-onset atrial fibrillation causing a mild acute diastolic congestive heart failure exacerbation. Transthoracic ECG showed a preserved left ventricular ejection fraction and no significant valvular disease. After two sessions of dialysis in the hospital and initiation of a beta-blocker for control of her heart rate, she is stable and ready for discharge. Her discharge weight is 75 kg.

Which of the following recommendations should you make to this patient regarding anticoagulation for prevention of stroke and systemic embolism from atrial fibrillation?

A. Take warfarin with a international normalized ratio goal of 2.5.

B. Take apixaban 2.5 mg twice a day.

C. Take apixaban 5 mg twice a day.

D. Discuss the risks/benefits of various treatment approaches with the patient, and involve the hospital pharmacist as well as the patient’s nephrologist, cardiologist, and/or primary care provider in the decision making process to reach a consensus and to ensure a safe follow-up plan.

The best answer is D. While A, B, and C are all reasonable approaches based on the available data and current guidelines, the best approach is to involve the patient and the multidisciplinary team in the decision making process. When more clinical trial data becomes available in the future, the optimal approach to managing patients such as this one may become clearer, but until then it makes sense to take into account individual patient characteristics and patient preferences.

Case

A 78-year-old woman with end-stage renal disease (ESRD) is hospitalized with cellulitis and is incidentally found to be in atrial fibrillation. She does not have a history of mitral stenosis, nor does she have a prosthetic valve. She does have a history of hypertension, diabetes, and prior stroke without residual deficits.

After counseling her about the risk of stroke associated with atrial fibrillation (AFib) she makes it clear she is interested in pharmacologic therapy to minimize her risk of stroke and asks what medication you would recommend for anticoagulation.

Brief overview of the issue

Anticoagulation for AFib is indicated for stroke prophylaxis in patients with an elevated risk of stroke. The CHA₂DS₂-VASc score is useful in calculating an individual patient’s risk of stroke and as a decision tool to determine who would benefit from anticoagulation, and it is recommended in the American Heart Association guidelines.¹

Low-risk patients (CHA₂DS₂-VASc score of 0 in men or 1 in women) should not be started on anticoagulation for stroke prophylaxis. For anyone with a risk factor, other than being female, anticoagulation is indicated and should be considered.

The guideline recommends anticoagulant therapy, not antiplatelet agents. For most of the recent past, this has meant a vitamin K antagonist (warfarin) or sometimes a low-molecular-weight heparin injected subcutaneously. Over the past decade, however, with the approval of multiple direct oral anticoagulants (DOACs), nonwarfarin oral anticoagulation has grown in popularity as the prophylactic medication of choice.²

While the data for patients with preserved renal function is robust, there is far less data to guide decision making for patients with end-stage renal disease.

Overview of the data

Until the introduction of DOACs, warfarin was the main agent used for stroke prophylaxis in patients with end-stage kidney disease and AFib. Professional guidelines favored warfarin for these patients who were mostly excluded from DOAC trials. Specialized conferences also looked at this issue.

The Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference, which reviewed chronic kidney disease and arrhythmias, noted that there were no randomized controlled trials that examined the efficacy and safety of anticoagulation in chronic kidney disease patients with estimated creatinine clearance less than 30 mL/min. They remarked that there was insufficient high-quality evidence to recommend warfarin for the prevention of stroke in patients with AFib and dialysis-dependent chronic kidney disease.

Since, according to other trials, DOACs had better safety profiles in other populations, the conference noted that lower-dose apixaban (2.5 mg orally twice daily) or rivaroxaban (15 mg daily) may be considered in this population until clinical safety data were available. Furthermore, the conference recommended that these patients be treated with a multidisciplinary approach in regards to anticoagulation and have an annual reevaluation of treatment goals, along with a risk-benefit assessment.³

Since the publication of the 2018 AHA guidelines and the guidance document that resulted from the KDIGO conference, additional research has been published comparing anticoagulation with a DOAC versus warfarin for AFib in patients with ESRD.

“Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the United States” was an observational, retrospective, cohort study that compared outcomes in dialysis patients who took warfarin for AFib with those who took apixaban.⁴ Patients’ data was taken from the U.S. Renal Data System database and were included in the final analysis if they had ESRD, a recent diagnosis of AFib or atrial flutter, and a new prescription for either warfarin or apixaban. Outcome measures were stroke or systemic embolism, major bleeding (critical site, transfusion, or death), gastrointestinal bleeding, intracranial bleeding, or death. Drug usage and compliance were assessed using Medicare Part D prescription information.

A total of 25,523 patients met the inclusion/exclusion criteria and had taken either warfarin (n = 23,172) or apixaban (n = 2,351). To account for selection bias in these cohorts, a subset of the warfarin patients was selected based on prognostic score matching. The prognostic score was calculated from the baseline characteristics (which included age, stroke history, diabetes, smoking, antiplatelet medication, liver disease, prior bleeding, and CHA₂DS₂-VASc score). Kaplan-Meier and Cox regression analysis were used to give hazard ratios and 95% confidence intervals for each outcome measure. Prespecified subgroup analyses were conducted to compare apixaban doses, where 44% were prescribed 5 mg b.i.d. and 56% were prescribed 2.5 mg b.i.d..

In the study, patients in the apixaban group had a significantly lower risk of major bleeding as compared with the warfarin group (HR, 0.72; 95% CI, 0.59-0.87; P less than .001) with overall high rates of major bleeding in both groups at 19.7 and 22.9 per 100 patient-years in the apixaban group and warfarin group, respectively. There was no difference in the rate of stroke/systemic embolism between patients receiving apixaban and warfarin (HR, 0.88; 95% CI, 0.69-1.12; P = .29). There was a nonsignificant trend toward decreased risk of GI bleeding in the apixaban group and no significant differences between the groups in the rates of intracranial bleeding. Apixaban was also associated with a nonsignificant trend toward lower risk of mortality (HR, 0.85; 95% CI, 0.71-1.01; P = .06).

Notably, censoring rates because of expired prescriptions or a 1-month gap between prescriptions were high in both groups and the majority of censoring occurred within the first 12 months. Additionally, in dose specific analyses, patients receiving the 5-mg, twice-daily dose were found to have statistically significant decreases in risk of stroke/systemic embolism (P = .035) and mortality (P = .005) as compared with the 2.5-mg, twice-daily dose without significant differences in GI or intracranial bleeding.

There are three ongoing, open-label, randomized, controlled trials examining anticoagulation for nonvalvular AFib in patients with ESRD on hemodialysis with two comparing apixaban to warfarin (or derivative) and the other warfarin versus no anticoagulation.⁵ All trials are in adult patients with documented AFib and CHA₂DS₂-VASc score of at least 2. AKADIA (Germany based) plans to enroll 222 patients and compares a vitamin K antagonist (INR goal, 2-3) with 2.5-mg b.i.d. apixaban patients with ESRD on hemodialysis for at least 3 months with primary outcome of major and clinically relevant nonmajor bleeding and secondary outcome of thromboembolic events, as well as apixaban levels pre- and post hemodialysis.

RENAL-AF (U.S. based) plans to enrolled 762 patients and compares 5-mg b.i.d. apixaban (with 2.5 mg for selected patients) with warfarin in people of chronic hemodialysis with primary outcome of days to first major or clinically relevant nonmajor bleeding event and secondary outcome of stroke, systemic embolism, mortality, adherence and plasma apixaban levels. AVKDIAL (France based) plans to enroll 855 patients and compares no anticoagulation with vitamin K antagonists in patients on hemodialysis for at least 1 month, with primary outcome of cumulative incidence of severe bleeding and thrombosis.

Application of the data to our original case

Our patient is Medicare age with ESRD and newly diagnosed nonvalvular AFib. Recent data suggests apixaban could be used for stroke prevention instead of the prior standard of care, warfarin. This approach is supported in the 2019 guidelines.¹

Patients with ESRD have an increased risk of bleeding and apixaban was shown to have less bleeding complications than warfarin in this analysis. However, only standard-dose apixaban was associated with a statistically significant lower risk of stroke/systemic embolism, major bleeding, and death. Reduced-dose apixaban had a lower risk of major bleeding but no difference for stroke/systemic embolism or death. Reduced-dose apixaban is used for patients who have two out of the following three criteria: aged at least 80 years, weight of at least 60 kg, and creatinine of at least 1.5 mg/dL. Therefore, many Medicare-age patients with ESRD would not be indicated for the dose of apixaban that was shown to improve the most important outcomes of stroke/SE and death.

It may still be beneficial to use apixaban in this patient since it appears to work as well as warfarin for stroke/systemic embolism prevention with less bleeding complications.

Bottom line

For patients who have decided to pursue an anticoagulation strategy for stroke prevention in AFib and have end-stage renal disease, either warfarin or apixaban are sensible options.

Dr. Farber is a medical instructor at Duke University Health System in Durham, N.C. Dr. Stafford is a medical instructor at Duke University. Dr. Sata is assistant professor of medicine at Duke University. Dr. Abdo and Dr. Menon are hospitalists at Duke University. Dr. Brooks is assistant professor of medicine at Duke University. Dr. Wachter is associate medical director at Duke Regional Hospital and assistant professor of medicine at Duke University. Dr. Sharma is associate medical director for clinical education in hospital medicine at Duke Regional Hospital and assistant professor of medicine at Duke University.

References

1. January CT et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2019;139. doi: 1161/CIR.0000000000000665.

2. Lippi G et al. Direct oral anticoagulants: Analysis of worldwide use and popularity using Google Trends. Ann Transl Med. 2017 Aug; 5(16):322. doi: 10.21037/atm.2017.06.65.

3. Turakhia MP et al. Chronic kidney disease and arrhythmias: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Eur Heart J. 2018 Jun 21;39(24):2314-25. doi: 10.1093/eurheartj/ehy060.

4. Siontis KC et al. Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the United States. Circulation. 2018 Oct 9;138(15):1519-29. doi: 10.1161/CIRCULATIONAHA.118.035418.

5. Nigwekar SU et al. Long-term anticoagulation for patient receiving dialysis: Tilting the benefit-to-risk ratio? Circulation. 2018 Oct 9;138(15):1530-3. doi: 10.1161/CIRCULATIONAHA.118.037091.

Key points

• According to 2019 American Heart Association guidelines, warfarin or apixaban are reasonable options for stroke prevention for patients who have end-stage renal disease and who plan for anticoagulation because of atrial fibrillation.
• Recent observational data suggests that apixaban may be safer than warfarin in this population.
• Several randomized, controlled trials are ongoing that may help determine the optimal agent to use in this setting.
• Until more definitive data is available, a reasonable approach is to discuss the risks and benefits of various treatment strategies with patients, and engage a multidisciplinary team (cardiologist, nephrologist, primary care provider, pharmacist) in the decision making process.

Additional reading

January CT et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2019;139. doi: 1161/CIR.0000000000000665.

Nigwekar SU et al. Long-term anticoagulation for patient receiving dialysis: Tilting the benefit to risk ratio? Circulation. 2018 Oct 9;138(15):1530-3. doi: 10.1161/CIRCULATIONAHA.118.037091.

Garlo KG et al. Demystifying the benefits and harms of anticoagulation for atrial fibrillation in chronic kidney disease. Clin J Am Soc Nephrol 2019;14:125-36. doi: 10.2215/CJN.06430518.

Quiz

Two days ago you admitted a 72-year-old woman with end-stage renal disease on dialysis who had developed new-onset atrial fibrillation causing a mild acute diastolic congestive heart failure exacerbation. Transthoracic ECG showed a preserved left ventricular ejection fraction and no significant valvular disease. After two sessions of dialysis in the hospital and initiation of a beta-blocker for control of her heart rate, she is stable and ready for discharge. Her discharge weight is 75 kg.

Which of the following recommendations should you make to this patient regarding anticoagulation for prevention of stroke and systemic embolism from atrial fibrillation?

A. Take warfarin with a international normalized ratio goal of 2.5.

B. Take apixaban 2.5 mg twice a day.

C. Take apixaban 5 mg twice a day.

D. Discuss the risks/benefits of various treatment approaches with the patient, and involve the hospital pharmacist as well as the patient’s nephrologist, cardiologist, and/or primary care provider in the decision making process to reach a consensus and to ensure a safe follow-up plan.

The best answer is D. While A, B, and C are all reasonable approaches based on the available data and current guidelines, the best approach is to involve the patient and the multidisciplinary team in the decision making process. When more clinical trial data becomes available in the future, the optimal approach to managing patients such as this one may become clearer, but until then it makes sense to take into account individual patient characteristics and patient preferences.

Case

An 85-year-old man with long-standing chronic obstructive pulmonary disease (COPD) has a witnessed aspiration event while undergoing an outpatient procedure requiring conscious sedation. He is admitted to the hospital for observation overnight. The next morning, he feels well, but his oxygen saturation dips to 85% with ambulation. He reports this is not new for him, but he vehemently does not want supplemental oxygen.

Background

Patients with COPD and severe resting hypoxemia – arterial oxygen partial pressure less than or equal to 55 mm Hg or peripheral capillary oxygen saturation (SpO₂₎ less than or equal to 88% – commonly are prescribed supplemental oxygen. The evidence supporting this practice is limited to two small trials from the 1970s that showed a survival benefit of long-term oxygen therapy (LTOT) in this population,^1,2 but these trials may not be generalizable to patients today.

For patients with COPD and mild to moderate resting hypoxemia (SpO_2, 89%-93%) or patients with exercise-induced hypoxemia, LTOT has not been shown to improve survival, although it may improve symptoms of dyspnea, exercise tolerance, and other patient reported outcomes. Given the costs, risks, and burdens associated with LTOT, a high-quality clinical trial assessing the effects of LTOT on clinically meaningful outcomes, such as survival or hospitalization, in patients with COPD and moderate hypoxemia has been long overdue.
 

Overview of the data

The utility of long-term treatment with supplemental oxygen in patients with stable COPD and moderate resting or exercise-induced desaturation was examined by the Long-Term Oxygen Treatment Trial (LOTT) Research Group. Results were published in the New England Journal of Medicine in October 2016 in the article, “A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation.”³

The study was initially designed to test whether the use of supplemental oxygen would lead to longer time until death as compared with no supplemental oxygen in the subgroup of COPD patients with stable disease and moderate resting desaturation (defined as resting SpO₂ of 89%-93%). However, because of an enrollment of only 34 patients after 7 months, the trial was redesigned to include exercise-induced desaturation (defined as SpO₂ of greater than or equal to 80% for at least 5 minutes, and less than 90% for at least 10 seconds, on a 6-minute walk test) and the secondary outcome of all-cause hospitalization. Hospitalization for any cause was combined with mortality into a new composite primary outcome.

This study was a randomized, controlled trial which enrolled patients at a total of 14 regional clinical centers and their associated sites for a total of 42 centers in the United States. The experimental arm consisted of a long term supplemental oxygen group, and the control group did not receive long term supplemental oxygen. Patients were assigned to groups in a 1:1 ratio and the study was not blinded. Patients with moderate resting desaturation were prescribed 24 hour oxygen at 2 L/min, and patients with moderate exercise-induced desaturation were prescribed oxygen at 2 L/min during exercise and sleep only. The primary outcome was a composite outcome of time until death or time until first hospitalization for any cause. There were multiple secondary outcomes, including incidence of COPD exacerbation, incidence of severe resting desaturation and severe exercise-induced desaturation, quality of life, sleep quality, depression and anxiety, adherence to regimen, 6-minute walk distance, spirometric measurements, risk of cardiovascular disease, and neurocognitive function.

Data were gathered via yearly visits, biannual telephone interviews, and questionnaires mailed at 4 months and 16 months. Adherence was assessed by inquiring about oxygen use every 4 months. If patients in the supplemental oxygen group used stationary oxygen concentrators, logs of meter readings were kept as well. The necessary final sample size was calculated using a time to composite event survival model with the use of the log-rank test statistic.

A total of 738 patients were enrolled in the trial between January 2009 and September 2015 and were followed for 1-6 years. A total of 97% of participants had at least 1 year of follow-up. Out of the 738 randomized patients, 133 (18%) had only resting desaturations, 319 (43%) had only exercise-induced desaturations, and 286 (39%) had both resting and exercise-induced desaturations. Baseline characteristics including age, sex, race, smoking status, quality of life scores, resting SpO_2, and nadir SpO₂ during the 6-minute walk test were similar between the two groups. The only significant difference noted by the authors between the two groups was a lower BODE (body mass index, airflow obstruction, dyspnea, and exercise) index, which was lower in the group with no supplemental oxygen.

In the time-to-event analysis, there was no significant difference between the two groups in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval, 0.79-1.12; P = .52). There were no significant differences in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91-1.13), COPD exacerbations (RR 1.08; 95% CI, 0.98-1.19), and COPD related hospitalizations (RR, 0.99; 95% CI, 0.83-1.17). There were also no differences between the experimental and control groups in quality of life, lung function, and 6-minute walk distance. There were no significant differences in the subgroups classified by desaturation profile, sex, race, nadir SpO₂ during the 6-minute walk test, and forced expiratory volume in 1 second.

The findings in this study show that, in the subgroup of chronic obstructive pulmonary disease patients with stable COPD and moderate resting or exercise-induced desaturation, supplemental oxygen did not affect the time to death or first hospitalization, time to death, time to first hospitalization, time to first COPD exacerbation, time to first hospitalization for a COPD exacerbation, rate of all hospitalizations, rate of all COPD exacerbations, or changes in metrics surrounding quality of life, anxiety/depression, or functional status. This supports earlier studies that demonstrated that long-term treatment with oxygen does not result in longer survival than does no long-term treatment with oxygen in patients with COPD and resting SpO₂ of more than 88%.

The results of this study are a departure from previous studies that had shown improved mortality in patients with COPD and severe desaturation who were treated with LTOT. The authors hypothesized that this may have been caused by physiological effects of oxygen saturation on pulmonary vasoconstriction, release of mediators, and ventilator drive, which occur at an O₂ saturation of 88% or less and may be more significant in patients with chronic hypoxemia. This trial also contrasted previous studies that had shown that oxygen therapy may reduce dyspnea in COPD patients with mild or no hypoxia because the LOTT trial showed no improvement in quality of life, anxiety, and depression measures in patients treated with long-term oxygen as compared with those treated with no oxygen.

Some limitations of the study included the absence of highly symptomatic patients or patients who the providers believed were too ill to participate, the effect of the unblinded nature of the study on outcomes that were patient reported, the lack of assessment of immediate effects of oxygen on exercise performance or symptoms, possible variability in amount of oxygen delivered, and the fact that patients may have overestimated their oxygen use.

In patients with stable COPD and moderate resting or exercise induced desaturation, long-term supplemental oxygen did not provide any benefit in regard to time until death or first hospitalization or any of the other measured outcomes.

Application of data to the case

Our patient has stable COPD and had only moderate exercise-induced desaturation. Long-term supplemental oxygen would not produce a benefit for him.

This study shows us that it would not increase his survival at this point; however, if he were to have worsening exercise-induced or new resting desaturation at some point in the future, supplemental oxygen would then be beneficial. At this point supplemental oxygen would not even affect his rate of hospitalization for COPD- or non-COPD–related reasons. Perhaps most importantly, adding oxygen therapy would not affect his overall quality of life, including his functional status and mood.
 

Bottom line

The addition of supplemental oxygen is not helpful for patients with COPD who have chronic stable moderate hypoxia.

Dr. Farber is a medical instructor in the Duke University Health System in Durham, N.C. Dr. Sata is a medical instructor in the Duke University Hospital. Dr. Wachter is an assistant professor of medicine at Duke University. Dr. Sharma is associate medical director for clinical education in hospital medicine at Duke Regional Hospital and an assistant professor of medicine at Duke University.

References

1. Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: A clinical trial. Ann Intern Med. 1980 Sep;93(3):391-8.

2. Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema: Report of the Medical Research Council Working Party. Lancet 1981 Mar 28;1(8222):681-6.

3. Long-term oxygen treatment trial research group et al. A randomized trial of long-term oxygen for COPD with moderate desaturation. N Engl J Med. 2016 Oct 27;375(17):1617-27.

Additional reading

Stoller JK et al. Oxygen therapy for patients with COPD: Current evidence and the Long-term Oxygen Treatment Trial. Chest. 2010 July;138:179-87.

Qaseem A et al. Diagnosis and management of stable chronic obstructive pulmonary disease: A clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011 Aug 2;155(3):179-91.

Ameer F et al. Ambulatory oxygen for people with chronic obstructive pulmonary disease who are not hypoxaemic at rest. Cochrane Database Syst Rev. 2014 Jun 24;(6):CD000238.

Vestbo J et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65.

Quiz: Does this patient need oxygen?

You are caring for a 72-year-old man with stable COPD who was admitted for cellulitis. He is improving clinically on appropriate antibiotics, and he has been stable on room air every time you examine him. The nurse pages you on the day of discharge – a Sunday – informing you that his oxygen saturation dropped to 88% while he was walking the halls this morning. She asks whether he needs to stay in the hospital so you can arrange home supplemental oxygen therapy. What should you do?

A. Keep him in the hospital until you can arrange home oxygen therapy.

B. Discharge him home Sunday but have the oxygen company go out to his house first thing on Monday.

C. Discharge him home without supplemental oxygen therapy.

D. Check an arterial blood gas to help decide if you should set up oxygen therapy.

The answer is C. He meets the description of stable COPD with mild to moderate exercise-induced desaturation. The LOTT trial supports our clinical decision that he would not benefit from supplemental oxygen therapy at this point.

Key Points

• Long-term oxygen therapy (LTOT) is beneficial in patients with COPD and severe resting hypoxemia (arterial oxygen partial pressure ≤ 55 mm Hg or SpO₂ ≤ 88%) and should be prescribed to improve survival in this population.
• Patients with COPD and mild to moderate resting hypoxemia or exercised-induced hypoxemia should not be routinely prescribed LTOT given the associated costs, risks, and burdens and the lack of evidence of benefit.

Case

An 85-year-old man with long-standing chronic obstructive pulmonary disease (COPD) has a witnessed aspiration event while undergoing an outpatient procedure requiring conscious sedation. He is admitted to the hospital for observation overnight. The next morning, he feels well, but his oxygen saturation dips to 85% with ambulation. He reports this is not new for him, but he vehemently does not want supplemental oxygen.

Background

Patients with COPD and severe resting hypoxemia – arterial oxygen partial pressure less than or equal to 55 mm Hg or peripheral capillary oxygen saturation (SpO₂₎ less than or equal to 88% – commonly are prescribed supplemental oxygen. The evidence supporting this practice is limited to two small trials from the 1970s that showed a survival benefit of long-term oxygen therapy (LTOT) in this population,^1,2 but these trials may not be generalizable to patients today.

For patients with COPD and mild to moderate resting hypoxemia (SpO_2, 89%-93%) or patients with exercise-induced hypoxemia, LTOT has not been shown to improve survival, although it may improve symptoms of dyspnea, exercise tolerance, and other patient reported outcomes. Given the costs, risks, and burdens associated with LTOT, a high-quality clinical trial assessing the effects of LTOT on clinically meaningful outcomes, such as survival or hospitalization, in patients with COPD and moderate hypoxemia has been long overdue.
 

Overview of the data

The utility of long-term treatment with supplemental oxygen in patients with stable COPD and moderate resting or exercise-induced desaturation was examined by the Long-Term Oxygen Treatment Trial (LOTT) Research Group. Results were published in the New England Journal of Medicine in October 2016 in the article, “A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation.”³

The study was initially designed to test whether the use of supplemental oxygen would lead to longer time until death as compared with no supplemental oxygen in the subgroup of COPD patients with stable disease and moderate resting desaturation (defined as resting SpO₂ of 89%-93%). However, because of an enrollment of only 34 patients after 7 months, the trial was redesigned to include exercise-induced desaturation (defined as SpO₂ of greater than or equal to 80% for at least 5 minutes, and less than 90% for at least 10 seconds, on a 6-minute walk test) and the secondary outcome of all-cause hospitalization. Hospitalization for any cause was combined with mortality into a new composite primary outcome.

This study was a randomized, controlled trial which enrolled patients at a total of 14 regional clinical centers and their associated sites for a total of 42 centers in the United States. The experimental arm consisted of a long term supplemental oxygen group, and the control group did not receive long term supplemental oxygen. Patients were assigned to groups in a 1:1 ratio and the study was not blinded. Patients with moderate resting desaturation were prescribed 24 hour oxygen at 2 L/min, and patients with moderate exercise-induced desaturation were prescribed oxygen at 2 L/min during exercise and sleep only. The primary outcome was a composite outcome of time until death or time until first hospitalization for any cause. There were multiple secondary outcomes, including incidence of COPD exacerbation, incidence of severe resting desaturation and severe exercise-induced desaturation, quality of life, sleep quality, depression and anxiety, adherence to regimen, 6-minute walk distance, spirometric measurements, risk of cardiovascular disease, and neurocognitive function.

Data were gathered via yearly visits, biannual telephone interviews, and questionnaires mailed at 4 months and 16 months. Adherence was assessed by inquiring about oxygen use every 4 months. If patients in the supplemental oxygen group used stationary oxygen concentrators, logs of meter readings were kept as well. The necessary final sample size was calculated using a time to composite event survival model with the use of the log-rank test statistic.

A total of 738 patients were enrolled in the trial between January 2009 and September 2015 and were followed for 1-6 years. A total of 97% of participants had at least 1 year of follow-up. Out of the 738 randomized patients, 133 (18%) had only resting desaturations, 319 (43%) had only exercise-induced desaturations, and 286 (39%) had both resting and exercise-induced desaturations. Baseline characteristics including age, sex, race, smoking status, quality of life scores, resting SpO_2, and nadir SpO₂ during the 6-minute walk test were similar between the two groups. The only significant difference noted by the authors between the two groups was a lower BODE (body mass index, airflow obstruction, dyspnea, and exercise) index, which was lower in the group with no supplemental oxygen.

In the time-to-event analysis, there was no significant difference between the two groups in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval, 0.79-1.12; P = .52). There were no significant differences in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91-1.13), COPD exacerbations (RR 1.08; 95% CI, 0.98-1.19), and COPD related hospitalizations (RR, 0.99; 95% CI, 0.83-1.17). There were also no differences between the experimental and control groups in quality of life, lung function, and 6-minute walk distance. There were no significant differences in the subgroups classified by desaturation profile, sex, race, nadir SpO₂ during the 6-minute walk test, and forced expiratory volume in 1 second.

The findings in this study show that, in the subgroup of chronic obstructive pulmonary disease patients with stable COPD and moderate resting or exercise-induced desaturation, supplemental oxygen did not affect the time to death or first hospitalization, time to death, time to first hospitalization, time to first COPD exacerbation, time to first hospitalization for a COPD exacerbation, rate of all hospitalizations, rate of all COPD exacerbations, or changes in metrics surrounding quality of life, anxiety/depression, or functional status. This supports earlier studies that demonstrated that long-term treatment with oxygen does not result in longer survival than does no long-term treatment with oxygen in patients with COPD and resting SpO₂ of more than 88%.

The results of this study are a departure from previous studies that had shown improved mortality in patients with COPD and severe desaturation who were treated with LTOT. The authors hypothesized that this may have been caused by physiological effects of oxygen saturation on pulmonary vasoconstriction, release of mediators, and ventilator drive, which occur at an O₂ saturation of 88% or less and may be more significant in patients with chronic hypoxemia. This trial also contrasted previous studies that had shown that oxygen therapy may reduce dyspnea in COPD patients with mild or no hypoxia because the LOTT trial showed no improvement in quality of life, anxiety, and depression measures in patients treated with long-term oxygen as compared with those treated with no oxygen.

Some limitations of the study included the absence of highly symptomatic patients or patients who the providers believed were too ill to participate, the effect of the unblinded nature of the study on outcomes that were patient reported, the lack of assessment of immediate effects of oxygen on exercise performance or symptoms, possible variability in amount of oxygen delivered, and the fact that patients may have overestimated their oxygen use.

In patients with stable COPD and moderate resting or exercise induced desaturation, long-term supplemental oxygen did not provide any benefit in regard to time until death or first hospitalization or any of the other measured outcomes.

Application of data to the case

Our patient has stable COPD and had only moderate exercise-induced desaturation. Long-term supplemental oxygen would not produce a benefit for him.

This study shows us that it would not increase his survival at this point; however, if he were to have worsening exercise-induced or new resting desaturation at some point in the future, supplemental oxygen would then be beneficial. At this point supplemental oxygen would not even affect his rate of hospitalization for COPD- or non-COPD–related reasons. Perhaps most importantly, adding oxygen therapy would not affect his overall quality of life, including his functional status and mood.
 

Bottom line

The addition of supplemental oxygen is not helpful for patients with COPD who have chronic stable moderate hypoxia.

Dr. Farber is a medical instructor in the Duke University Health System in Durham, N.C. Dr. Sata is a medical instructor in the Duke University Hospital. Dr. Wachter is an assistant professor of medicine at Duke University. Dr. Sharma is associate medical director for clinical education in hospital medicine at Duke Regional Hospital and an assistant professor of medicine at Duke University.

References

1. Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: A clinical trial. Ann Intern Med. 1980 Sep;93(3):391-8.

2. Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema: Report of the Medical Research Council Working Party. Lancet 1981 Mar 28;1(8222):681-6.

3. Long-term oxygen treatment trial research group et al. A randomized trial of long-term oxygen for COPD with moderate desaturation. N Engl J Med. 2016 Oct 27;375(17):1617-27.

Additional reading

Stoller JK et al. Oxygen therapy for patients with COPD: Current evidence and the Long-term Oxygen Treatment Trial. Chest. 2010 July;138:179-87.

Qaseem A et al. Diagnosis and management of stable chronic obstructive pulmonary disease: A clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011 Aug 2;155(3):179-91.

Ameer F et al. Ambulatory oxygen for people with chronic obstructive pulmonary disease who are not hypoxaemic at rest. Cochrane Database Syst Rev. 2014 Jun 24;(6):CD000238.

Vestbo J et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65.

Quiz: Does this patient need oxygen?

You are caring for a 72-year-old man with stable COPD who was admitted for cellulitis. He is improving clinically on appropriate antibiotics, and he has been stable on room air every time you examine him. The nurse pages you on the day of discharge – a Sunday – informing you that his oxygen saturation dropped to 88% while he was walking the halls this morning. She asks whether he needs to stay in the hospital so you can arrange home supplemental oxygen therapy. What should you do?

A. Keep him in the hospital until you can arrange home oxygen therapy.

B. Discharge him home Sunday but have the oxygen company go out to his house first thing on Monday.

C. Discharge him home without supplemental oxygen therapy.

D. Check an arterial blood gas to help decide if you should set up oxygen therapy.

The answer is C. He meets the description of stable COPD with mild to moderate exercise-induced desaturation. The LOTT trial supports our clinical decision that he would not benefit from supplemental oxygen therapy at this point.

Key Points

• Long-term oxygen therapy (LTOT) is beneficial in patients with COPD and severe resting hypoxemia (arterial oxygen partial pressure ≤ 55 mm Hg or SpO₂ ≤ 88%) and should be prescribed to improve survival in this population.
• Patients with COPD and mild to moderate resting hypoxemia or exercised-induced hypoxemia should not be routinely prescribed LTOT given the associated costs, risks, and burdens and the lack of evidence of benefit.

Case

An 85-year-old man with long-standing chronic obstructive pulmonary disease (COPD) has a witnessed aspiration event while undergoing an outpatient procedure requiring conscious sedation. He is admitted to the hospital for observation overnight. The next morning, he feels well, but his oxygen saturation dips to 85% with ambulation. He reports this is not new for him, but he vehemently does not want supplemental oxygen.

Background

Patients with COPD and severe resting hypoxemia – arterial oxygen partial pressure less than or equal to 55 mm Hg or peripheral capillary oxygen saturation (SpO₂₎ less than or equal to 88% – commonly are prescribed supplemental oxygen. The evidence supporting this practice is limited to two small trials from the 1970s that showed a survival benefit of long-term oxygen therapy (LTOT) in this population,^1,2 but these trials may not be generalizable to patients today.

For patients with COPD and mild to moderate resting hypoxemia (SpO_2, 89%-93%) or patients with exercise-induced hypoxemia, LTOT has not been shown to improve survival, although it may improve symptoms of dyspnea, exercise tolerance, and other patient reported outcomes. Given the costs, risks, and burdens associated with LTOT, a high-quality clinical trial assessing the effects of LTOT on clinically meaningful outcomes, such as survival or hospitalization, in patients with COPD and moderate hypoxemia has been long overdue.
 

Overview of the data

The utility of long-term treatment with supplemental oxygen in patients with stable COPD and moderate resting or exercise-induced desaturation was examined by the Long-Term Oxygen Treatment Trial (LOTT) Research Group. Results were published in the New England Journal of Medicine in October 2016 in the article, “A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation.”³

The study was initially designed to test whether the use of supplemental oxygen would lead to longer time until death as compared with no supplemental oxygen in the subgroup of COPD patients with stable disease and moderate resting desaturation (defined as resting SpO₂ of 89%-93%). However, because of an enrollment of only 34 patients after 7 months, the trial was redesigned to include exercise-induced desaturation (defined as SpO₂ of greater than or equal to 80% for at least 5 minutes, and less than 90% for at least 10 seconds, on a 6-minute walk test) and the secondary outcome of all-cause hospitalization. Hospitalization for any cause was combined with mortality into a new composite primary outcome.

This study was a randomized, controlled trial which enrolled patients at a total of 14 regional clinical centers and their associated sites for a total of 42 centers in the United States. The experimental arm consisted of a long term supplemental oxygen group, and the control group did not receive long term supplemental oxygen. Patients were assigned to groups in a 1:1 ratio and the study was not blinded. Patients with moderate resting desaturation were prescribed 24 hour oxygen at 2 L/min, and patients with moderate exercise-induced desaturation were prescribed oxygen at 2 L/min during exercise and sleep only. The primary outcome was a composite outcome of time until death or time until first hospitalization for any cause. There were multiple secondary outcomes, including incidence of COPD exacerbation, incidence of severe resting desaturation and severe exercise-induced desaturation, quality of life, sleep quality, depression and anxiety, adherence to regimen, 6-minute walk distance, spirometric measurements, risk of cardiovascular disease, and neurocognitive function.

Data were gathered via yearly visits, biannual telephone interviews, and questionnaires mailed at 4 months and 16 months. Adherence was assessed by inquiring about oxygen use every 4 months. If patients in the supplemental oxygen group used stationary oxygen concentrators, logs of meter readings were kept as well. The necessary final sample size was calculated using a time to composite event survival model with the use of the log-rank test statistic.

A total of 738 patients were enrolled in the trial between January 2009 and September 2015 and were followed for 1-6 years. A total of 97% of participants had at least 1 year of follow-up. Out of the 738 randomized patients, 133 (18%) had only resting desaturations, 319 (43%) had only exercise-induced desaturations, and 286 (39%) had both resting and exercise-induced desaturations. Baseline characteristics including age, sex, race, smoking status, quality of life scores, resting SpO_2, and nadir SpO₂ during the 6-minute walk test were similar between the two groups. The only significant difference noted by the authors between the two groups was a lower BODE (body mass index, airflow obstruction, dyspnea, and exercise) index, which was lower in the group with no supplemental oxygen.

In the time-to-event analysis, there was no significant difference between the two groups in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval, 0.79-1.12; P = .52). There were no significant differences in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91-1.13), COPD exacerbations (RR 1.08; 95% CI, 0.98-1.19), and COPD related hospitalizations (RR, 0.99; 95% CI, 0.83-1.17). There were also no differences between the experimental and control groups in quality of life, lung function, and 6-minute walk distance. There were no significant differences in the subgroups classified by desaturation profile, sex, race, nadir SpO₂ during the 6-minute walk test, and forced expiratory volume in 1 second.

The findings in this study show that, in the subgroup of chronic obstructive pulmonary disease patients with stable COPD and moderate resting or exercise-induced desaturation, supplemental oxygen did not affect the time to death or first hospitalization, time to death, time to first hospitalization, time to first COPD exacerbation, time to first hospitalization for a COPD exacerbation, rate of all hospitalizations, rate of all COPD exacerbations, or changes in metrics surrounding quality of life, anxiety/depression, or functional status. This supports earlier studies that demonstrated that long-term treatment with oxygen does not result in longer survival than does no long-term treatment with oxygen in patients with COPD and resting SpO₂ of more than 88%.

The results of this study are a departure from previous studies that had shown improved mortality in patients with COPD and severe desaturation who were treated with LTOT. The authors hypothesized that this may have been caused by physiological effects of oxygen saturation on pulmonary vasoconstriction, release of mediators, and ventilator drive, which occur at an O₂ saturation of 88% or less and may be more significant in patients with chronic hypoxemia. This trial also contrasted previous studies that had shown that oxygen therapy may reduce dyspnea in COPD patients with mild or no hypoxia because the LOTT trial showed no improvement in quality of life, anxiety, and depression measures in patients treated with long-term oxygen as compared with those treated with no oxygen.

Some limitations of the study included the absence of highly symptomatic patients or patients who the providers believed were too ill to participate, the effect of the unblinded nature of the study on outcomes that were patient reported, the lack of assessment of immediate effects of oxygen on exercise performance or symptoms, possible variability in amount of oxygen delivered, and the fact that patients may have overestimated their oxygen use.

In patients with stable COPD and moderate resting or exercise induced desaturation, long-term supplemental oxygen did not provide any benefit in regard to time until death or first hospitalization or any of the other measured outcomes.

Application of data to the case

Our patient has stable COPD and had only moderate exercise-induced desaturation. Long-term supplemental oxygen would not produce a benefit for him.

This study shows us that it would not increase his survival at this point; however, if he were to have worsening exercise-induced or new resting desaturation at some point in the future, supplemental oxygen would then be beneficial. At this point supplemental oxygen would not even affect his rate of hospitalization for COPD- or non-COPD–related reasons. Perhaps most importantly, adding oxygen therapy would not affect his overall quality of life, including his functional status and mood.
 

Bottom line

The addition of supplemental oxygen is not helpful for patients with COPD who have chronic stable moderate hypoxia.

Dr. Farber is a medical instructor in the Duke University Health System in Durham, N.C. Dr. Sata is a medical instructor in the Duke University Hospital. Dr. Wachter is an assistant professor of medicine at Duke University. Dr. Sharma is associate medical director for clinical education in hospital medicine at Duke Regional Hospital and an assistant professor of medicine at Duke University.

References

1. Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: A clinical trial. Ann Intern Med. 1980 Sep;93(3):391-8.

2. Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema: Report of the Medical Research Council Working Party. Lancet 1981 Mar 28;1(8222):681-6.

3. Long-term oxygen treatment trial research group et al. A randomized trial of long-term oxygen for COPD with moderate desaturation. N Engl J Med. 2016 Oct 27;375(17):1617-27.

Additional reading

Stoller JK et al. Oxygen therapy for patients with COPD: Current evidence and the Long-term Oxygen Treatment Trial. Chest. 2010 July;138:179-87.

Qaseem A et al. Diagnosis and management of stable chronic obstructive pulmonary disease: A clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011 Aug 2;155(3):179-91.

Ameer F et al. Ambulatory oxygen for people with chronic obstructive pulmonary disease who are not hypoxaemic at rest. Cochrane Database Syst Rev. 2014 Jun 24;(6):CD000238.

Vestbo J et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65.

Quiz: Does this patient need oxygen?

You are caring for a 72-year-old man with stable COPD who was admitted for cellulitis. He is improving clinically on appropriate antibiotics, and he has been stable on room air every time you examine him. The nurse pages you on the day of discharge – a Sunday – informing you that his oxygen saturation dropped to 88% while he was walking the halls this morning. She asks whether he needs to stay in the hospital so you can arrange home supplemental oxygen therapy. What should you do?

A. Keep him in the hospital until you can arrange home oxygen therapy.

B. Discharge him home Sunday but have the oxygen company go out to his house first thing on Monday.

C. Discharge him home without supplemental oxygen therapy.

D. Check an arterial blood gas to help decide if you should set up oxygen therapy.

The answer is C. He meets the description of stable COPD with mild to moderate exercise-induced desaturation. The LOTT trial supports our clinical decision that he would not benefit from supplemental oxygen therapy at this point.

Key Points

• Long-term oxygen therapy (LTOT) is beneficial in patients with COPD and severe resting hypoxemia (arterial oxygen partial pressure ≤ 55 mm Hg or SpO₂ ≤ 88%) and should be prescribed to improve survival in this population.
• Patients with COPD and mild to moderate resting hypoxemia or exercised-induced hypoxemia should not be routinely prescribed LTOT given the associated costs, risks, and burdens and the lack of evidence of benefit.

Clinical question: What is the content and structure of patient care–related text paging sent in the inpatient setting?

Background: Text paging has become a common form of communication among members of the inpatient multidisciplinary team, but there are potential risks and downsides of text paging, including disruptiveness, inefficiency, and potential patient safety issues.

Study Design: Modified case-study approach.

Setting: The medical inpatient service of an academic tertiary care hospital.

Synopsis: 575 text-page messages relating to 217 unique patients were analyzed in the study. The majority of the messages were sent from nonphysicians to physicians. Common themes that were identified included lack of standardization of textmessage content and format, lack of indicators of the urgency of the message, and lack of clarity within the message. Pertinent information sometimes was missing from the messages, and it was not always clear whether the sender was requesting a response from the recipient.

Bottom line: Text-paging practices may raise patient safety issues that could be addressed by implementation of a standardized, structured approach to this form of communication.

Citation: Luxenberg A et al. Efficiency and interpretability of text paging communication for medical inpatients: A mixed-methods analysis. JAMA Intern Med. 2017;177(8):1218-20.

Dr. Wachter is an assistant professor of medicine at Duke University

Clinical question: What is the content and structure of patient care–related text paging sent in the inpatient setting?

Background: Text paging has become a common form of communication among members of the inpatient multidisciplinary team, but there are potential risks and downsides of text paging, including disruptiveness, inefficiency, and potential patient safety issues.

Study Design: Modified case-study approach.

Setting: The medical inpatient service of an academic tertiary care hospital.

Synopsis: 575 text-page messages relating to 217 unique patients were analyzed in the study. The majority of the messages were sent from nonphysicians to physicians. Common themes that were identified included lack of standardization of textmessage content and format, lack of indicators of the urgency of the message, and lack of clarity within the message. Pertinent information sometimes was missing from the messages, and it was not always clear whether the sender was requesting a response from the recipient.

Bottom line: Text-paging practices may raise patient safety issues that could be addressed by implementation of a standardized, structured approach to this form of communication.

Citation: Luxenberg A et al. Efficiency and interpretability of text paging communication for medical inpatients: A mixed-methods analysis. JAMA Intern Med. 2017;177(8):1218-20.

Dr. Wachter is an assistant professor of medicine at Duke University

Clinical question: What is the content and structure of patient care–related text paging sent in the inpatient setting?

Background: Text paging has become a common form of communication among members of the inpatient multidisciplinary team, but there are potential risks and downsides of text paging, including disruptiveness, inefficiency, and potential patient safety issues.

Study Design: Modified case-study approach.

Setting: The medical inpatient service of an academic tertiary care hospital.

Synopsis: 575 text-page messages relating to 217 unique patients were analyzed in the study. The majority of the messages were sent from nonphysicians to physicians. Common themes that were identified included lack of standardization of textmessage content and format, lack of indicators of the urgency of the message, and lack of clarity within the message. Pertinent information sometimes was missing from the messages, and it was not always clear whether the sender was requesting a response from the recipient.

Bottom line: Text-paging practices may raise patient safety issues that could be addressed by implementation of a standardized, structured approach to this form of communication.

Citation: Luxenberg A et al. Efficiency and interpretability of text paging communication for medical inpatients: A mixed-methods analysis. JAMA Intern Med. 2017;177(8):1218-20.

Dr. Wachter is an assistant professor of medicine at Duke University

Clinical question: Which medications are most safe and effective at managing type 2 diabetes?

Background: Patients and practitioners need an updated review of the evidence to select the optimal medication for type 2 diabetes management.

Study design: Systematic review.

Synopsis: The authors reviewed 179 trials and 25 observational studies. When comparing metformin to sulfonylureas, metformin was associated with less cardiovascular mortality.

However, when trying to make comparisons based on all-cause mortality or microvascular complications, the evidence is limited. Improvements in hemoglobin A1c levels are similar when comparing different monotherapy options, and low blood sugar was most common with sulfonylureas. The short duration of many trials limits the ability to provide better data on long-term outcomes.

Bottom line: Metformin remains the first-line agent for type 2 diabetes management.

Citation: Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systemic review and meta-analysis. Ann Intern Med. 2016;164(1):740-751.

Short Take

Patients Discharge Readiness May Not Be Adequately Assessed and/or Addressed During Hospitalization

Prospective observational study found unresolved barriers to discharge were common in at least 90% of patients. Patients frequently cited issues including unresolved pain, lack of understanding around discharge plans, and ability to provide self-care.

Citation: Harrison JD, Greysen RS, Jacolbia R, Nguyen A, Auerbach AD. Not ready, not set…discharge: patient-reported barriers to discharge readiness at an academic medical center [published online ahead of print April 15, 2016]. J Hosp Med. doi:10.1002/jhm.2591.

Clinical question: Which medications are most safe and effective at managing type 2 diabetes?

Background: Patients and practitioners need an updated review of the evidence to select the optimal medication for type 2 diabetes management.

Study design: Systematic review.

Synopsis: The authors reviewed 179 trials and 25 observational studies. When comparing metformin to sulfonylureas, metformin was associated with less cardiovascular mortality.

However, when trying to make comparisons based on all-cause mortality or microvascular complications, the evidence is limited. Improvements in hemoglobin A1c levels are similar when comparing different monotherapy options, and low blood sugar was most common with sulfonylureas. The short duration of many trials limits the ability to provide better data on long-term outcomes.

Bottom line: Metformin remains the first-line agent for type 2 diabetes management.

Citation: Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systemic review and meta-analysis. Ann Intern Med. 2016;164(1):740-751.

Short Take

Patients Discharge Readiness May Not Be Adequately Assessed and/or Addressed During Hospitalization

Prospective observational study found unresolved barriers to discharge were common in at least 90% of patients. Patients frequently cited issues including unresolved pain, lack of understanding around discharge plans, and ability to provide self-care.

Citation: Harrison JD, Greysen RS, Jacolbia R, Nguyen A, Auerbach AD. Not ready, not set…discharge: patient-reported barriers to discharge readiness at an academic medical center [published online ahead of print April 15, 2016]. J Hosp Med. doi:10.1002/jhm.2591.

Clinical question: Which medications are most safe and effective at managing type 2 diabetes?

Background: Patients and practitioners need an updated review of the evidence to select the optimal medication for type 2 diabetes management.

Study design: Systematic review.

Synopsis: The authors reviewed 179 trials and 25 observational studies. When comparing metformin to sulfonylureas, metformin was associated with less cardiovascular mortality.

However, when trying to make comparisons based on all-cause mortality or microvascular complications, the evidence is limited. Improvements in hemoglobin A1c levels are similar when comparing different monotherapy options, and low blood sugar was most common with sulfonylureas. The short duration of many trials limits the ability to provide better data on long-term outcomes.

Bottom line: Metformin remains the first-line agent for type 2 diabetes management.

Citation: Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systemic review and meta-analysis. Ann Intern Med. 2016;164(1):740-751.

Short Take

Patients Discharge Readiness May Not Be Adequately Assessed and/or Addressed During Hospitalization

Prospective observational study found unresolved barriers to discharge were common in at least 90% of patients. Patients frequently cited issues including unresolved pain, lack of understanding around discharge plans, and ability to provide self-care.

Citation: Harrison JD, Greysen RS, Jacolbia R, Nguyen A, Auerbach AD. Not ready, not set…discharge: patient-reported barriers to discharge readiness at an academic medical center [published online ahead of print April 15, 2016]. J Hosp Med. doi:10.1002/jhm.2591.

Clinical question: What is the prognosis of patients who have a TIA or minor stroke?

Background: Prior studies had estimated the risk in the three months following a TIA or minor stroke of having a stroke or acute coronary syndrome (ACS) as 12% to 20%, but this may not reflect the risk of modern patients receiving the current standards of care.

Study design: Prospective observational registry of patients with recent TIA or minor stroke.

Setting: International, including 21 countries.

Synopsis: Adults with recent TIA or minor stroke were included in this multi-center, international registry, and one-year outcomes were reported. At one year, the Kaplan-Meier estimated event rate for the combined outcome of stroke, ACS, or death from cardiovascular causes was 6.2%. The risk of the cardiovascular events was found to be lower than previously reported, suggesting an improvement in outcomes with current interventions. Elevated ABCD2 score, infarction seen on brain imaging, and large-artery atherosclerosis were each associated with higher risk.

Bottom line: Elevated ABCD2 score, brain imaging findings, and large-artery atherosclerosis suggest increased risk for recurrent stroke.

Citation: Amarenco P, Lavallée PC, Labreuche J, et al. One-year risk of stroke after transient ischemic attack or minor stroke. N Engl J Med. 2016;374(16):1533-1542.

Clinical question: What is the prognosis of patients who have a TIA or minor stroke?

Background: Prior studies had estimated the risk in the three months following a TIA or minor stroke of having a stroke or acute coronary syndrome (ACS) as 12% to 20%, but this may not reflect the risk of modern patients receiving the current standards of care.

Study design: Prospective observational registry of patients with recent TIA or minor stroke.

Setting: International, including 21 countries.

Synopsis: Adults with recent TIA or minor stroke were included in this multi-center, international registry, and one-year outcomes were reported. At one year, the Kaplan-Meier estimated event rate for the combined outcome of stroke, ACS, or death from cardiovascular causes was 6.2%. The risk of the cardiovascular events was found to be lower than previously reported, suggesting an improvement in outcomes with current interventions. Elevated ABCD2 score, infarction seen on brain imaging, and large-artery atherosclerosis were each associated with higher risk.

Bottom line: Elevated ABCD2 score, brain imaging findings, and large-artery atherosclerosis suggest increased risk for recurrent stroke.

Citation: Amarenco P, Lavallée PC, Labreuche J, et al. One-year risk of stroke after transient ischemic attack or minor stroke. N Engl J Med. 2016;374(16):1533-1542.

Clinical question: What is the prognosis of patients who have a TIA or minor stroke?

Background: Prior studies had estimated the risk in the three months following a TIA or minor stroke of having a stroke or acute coronary syndrome (ACS) as 12% to 20%, but this may not reflect the risk of modern patients receiving the current standards of care.

Study design: Prospective observational registry of patients with recent TIA or minor stroke.

Setting: International, including 21 countries.

Synopsis: Adults with recent TIA or minor stroke were included in this multi-center, international registry, and one-year outcomes were reported. At one year, the Kaplan-Meier estimated event rate for the combined outcome of stroke, ACS, or death from cardiovascular causes was 6.2%. The risk of the cardiovascular events was found to be lower than previously reported, suggesting an improvement in outcomes with current interventions. Elevated ABCD2 score, infarction seen on brain imaging, and large-artery atherosclerosis were each associated with higher risk.

Bottom line: Elevated ABCD2 score, brain imaging findings, and large-artery atherosclerosis suggest increased risk for recurrent stroke.

Citation: Amarenco P, Lavallée PC, Labreuche J, et al. One-year risk of stroke after transient ischemic attack or minor stroke. N Engl J Med. 2016;374(16):1533-1542.

Clinical question: Is one dose of dexamethasone comparable to five days of prednisone for treating mild-to-moderate asthma exacerbations?

Background: Corticosteroids are the mainstay of initial treatment for asthma exacerbations. The National Heart, Lung, and Blood Institute recommends a minimum of five days of prednisone, though studies have shown incomplete adherence to prolonged therapies. Dexamethasone has a longer duration of action than prednisone.

Study design: Randomized, controlled, double-blinded trial.

Setting: Urban, safety-net, teaching hospital.

Synopsis: The study included 376 adults ages 18–55 presenting to the emergency department for a mild-to-moderate asthma exacerbation who were randomized to two treatment courses of corticosteroids: one 12 mg dose of oral dexamethasone followed by four days of placebo versus five days of 60 mg of oral prednisone. Two weeks later, a telephone survey asked if they had relapsed and had to seek medical attention. This study did not show noninferiority of the dexamethasone option compared to the standard of care. Specifically, it showed a 12.1% relapse rate in the dexamethasone group versus a 9.8% relapse rate for prednisone (95% CI, -4.1% to 8.6%).

This was a small study looking at adults without other chronic lung diseases or diabetes. The authors did not include those patients who were either lost to follow-up (20% of those initially randomized) or ultimately admitted after their emergency department course.

Hospitalists who care for patients with asthma should look to the current standards of corticosteroid selection and duration to minimize clinical relapses and possibly readmissions.

Bottom line: One large dose of dexamethasone is inferior to the standard five days of prednisone for treating acute asthma exacerbations in adults.

Citation: Rehrer MW, Liu B, Rodriguez M, Lam J, Alter HJ. A randomized controlled noninferiority trial of single dose of oral dexamethasone versus 5 days of oral prednisone in acute adult asthma [published online ahead of print April 14, 2016]. Ann Emerg Med. doi:10.1016/j.annemergmed.2016.03.017.

Short Take

Guideline Recommends ED Asthma Management Associated with Shorter Inpatient Stay

Observational study found ED treatment concordance with four guideline-based processes for acute asthma treatment (inhaled beta-agonists, inhaled anticholinergics, systemic corticosteroids, and avoidance of methylxanthines) is associated with a 17% shorter hospital length of stay.

Citation: Hasegawa K, Brenner BE, Nowak RM, et al. Association of guideline-concordant acute asthma care in the emergency department with shorter hospital length of stay: a multicenter observational study. Acad Emerg Med. 2016;23(5):616-622.

Clinical question: Is one dose of dexamethasone comparable to five days of prednisone for treating mild-to-moderate asthma exacerbations?

Background: Corticosteroids are the mainstay of initial treatment for asthma exacerbations. The National Heart, Lung, and Blood Institute recommends a minimum of five days of prednisone, though studies have shown incomplete adherence to prolonged therapies. Dexamethasone has a longer duration of action than prednisone.

Study design: Randomized, controlled, double-blinded trial.

Setting: Urban, safety-net, teaching hospital.

Synopsis: The study included 376 adults ages 18–55 presenting to the emergency department for a mild-to-moderate asthma exacerbation who were randomized to two treatment courses of corticosteroids: one 12 mg dose of oral dexamethasone followed by four days of placebo versus five days of 60 mg of oral prednisone. Two weeks later, a telephone survey asked if they had relapsed and had to seek medical attention. This study did not show noninferiority of the dexamethasone option compared to the standard of care. Specifically, it showed a 12.1% relapse rate in the dexamethasone group versus a 9.8% relapse rate for prednisone (95% CI, -4.1% to 8.6%).

This was a small study looking at adults without other chronic lung diseases or diabetes. The authors did not include those patients who were either lost to follow-up (20% of those initially randomized) or ultimately admitted after their emergency department course.

Hospitalists who care for patients with asthma should look to the current standards of corticosteroid selection and duration to minimize clinical relapses and possibly readmissions.

Bottom line: One large dose of dexamethasone is inferior to the standard five days of prednisone for treating acute asthma exacerbations in adults.

Citation: Rehrer MW, Liu B, Rodriguez M, Lam J, Alter HJ. A randomized controlled noninferiority trial of single dose of oral dexamethasone versus 5 days of oral prednisone in acute adult asthma [published online ahead of print April 14, 2016]. Ann Emerg Med. doi:10.1016/j.annemergmed.2016.03.017.

Short Take

Guideline Recommends ED Asthma Management Associated with Shorter Inpatient Stay

Observational study found ED treatment concordance with four guideline-based processes for acute asthma treatment (inhaled beta-agonists, inhaled anticholinergics, systemic corticosteroids, and avoidance of methylxanthines) is associated with a 17% shorter hospital length of stay.

Citation: Hasegawa K, Brenner BE, Nowak RM, et al. Association of guideline-concordant acute asthma care in the emergency department with shorter hospital length of stay: a multicenter observational study. Acad Emerg Med. 2016;23(5):616-622.

Clinical question: Is one dose of dexamethasone comparable to five days of prednisone for treating mild-to-moderate asthma exacerbations?

Background: Corticosteroids are the mainstay of initial treatment for asthma exacerbations. The National Heart, Lung, and Blood Institute recommends a minimum of five days of prednisone, though studies have shown incomplete adherence to prolonged therapies. Dexamethasone has a longer duration of action than prednisone.

Study design: Randomized, controlled, double-blinded trial.

Setting: Urban, safety-net, teaching hospital.

Synopsis: The study included 376 adults ages 18–55 presenting to the emergency department for a mild-to-moderate asthma exacerbation who were randomized to two treatment courses of corticosteroids: one 12 mg dose of oral dexamethasone followed by four days of placebo versus five days of 60 mg of oral prednisone. Two weeks later, a telephone survey asked if they had relapsed and had to seek medical attention. This study did not show noninferiority of the dexamethasone option compared to the standard of care. Specifically, it showed a 12.1% relapse rate in the dexamethasone group versus a 9.8% relapse rate for prednisone (95% CI, -4.1% to 8.6%).

This was a small study looking at adults without other chronic lung diseases or diabetes. The authors did not include those patients who were either lost to follow-up (20% of those initially randomized) or ultimately admitted after their emergency department course.

Hospitalists who care for patients with asthma should look to the current standards of corticosteroid selection and duration to minimize clinical relapses and possibly readmissions.

Bottom line: One large dose of dexamethasone is inferior to the standard five days of prednisone for treating acute asthma exacerbations in adults.

Citation: Rehrer MW, Liu B, Rodriguez M, Lam J, Alter HJ. A randomized controlled noninferiority trial of single dose of oral dexamethasone versus 5 days of oral prednisone in acute adult asthma [published online ahead of print April 14, 2016]. Ann Emerg Med. doi:10.1016/j.annemergmed.2016.03.017.

Short Take

Guideline Recommends ED Asthma Management Associated with Shorter Inpatient Stay

Observational study found ED treatment concordance with four guideline-based processes for acute asthma treatment (inhaled beta-agonists, inhaled anticholinergics, systemic corticosteroids, and avoidance of methylxanthines) is associated with a 17% shorter hospital length of stay.

Citation: Hasegawa K, Brenner BE, Nowak RM, et al. Association of guideline-concordant acute asthma care in the emergency department with shorter hospital length of stay: a multicenter observational study. Acad Emerg Med. 2016;23(5):616-622.

Clinical question: How do interhospital handoff practices differ among U.S. tertiary care centers, and what challenges and innovations have providers encountered?

Background: Little has been studied regarding interhospital transfers. Many centers differ in the processes they follow, and well-delineated national guidelines are lacking. Adverse events occur in up to 30% of transfers. Standardization of these handoffs has been shown to reduce preventable errors and near misses.

Study design: Survey of convenience sample of institutions.

Setting: Transfer center directors from 32 tertiary care centers in the U.S.

Synopsis: The authors surveyed directors of 32 transfer centers between 2013 and 2015. Hospitals were selected from a nationally ranked list as well as those comparable to the authors’ own institutions. The median number of patients transferred per month was 700.

Only 23% of hospitals surveyed identified significant EHR interoperability. Almost all required three-way recorded discussion between transfer center staff and referring and accepting physicians. Only 29% had available objective clinical information to share. Only 23% recorded a three-way nursing handoff, and only 32% used their EHR to document the transfer process and share clinical information among providers.

Innovations included electronic transfer notes, a standardized system of feedback to referring hospitals, automatic internal review for adverse events and delayed transfers, and use of a scorecard with key measures shared with stakeholders.

Barriers noted included complexity, acuity, and lack of continuity. Increased use of EHRs, checklists, and common processes were identified as best practices.

Limitations of the study included reliance on verbal qualitative data, a single investigator doing most of the discussions, and possible sampling bias.

Bottom line: Interhospital transfer practices at academic tertiary care centers vary widely, and optimizing and aligning practices between sending and receiving hospitals may improve efficiency and patient outcomes.

References: Herrigel DJ, Carroll M, Fanning C, Steinberg MB, Parikh A, Usher M. Interhospital transfer handoff practices among US tertiary care centers: a descriptive survey. J Hosp Med. 2016;11(6):413-417.

Clinical question: How do interhospital handoff practices differ among U.S. tertiary care centers, and what challenges and innovations have providers encountered?

Background: Little has been studied regarding interhospital transfers. Many centers differ in the processes they follow, and well-delineated national guidelines are lacking. Adverse events occur in up to 30% of transfers. Standardization of these handoffs has been shown to reduce preventable errors and near misses.

Study design: Survey of convenience sample of institutions.

Setting: Transfer center directors from 32 tertiary care centers in the U.S.

Synopsis: The authors surveyed directors of 32 transfer centers between 2013 and 2015. Hospitals were selected from a nationally ranked list as well as those comparable to the authors’ own institutions. The median number of patients transferred per month was 700.

Only 23% of hospitals surveyed identified significant EHR interoperability. Almost all required three-way recorded discussion between transfer center staff and referring and accepting physicians. Only 29% had available objective clinical information to share. Only 23% recorded a three-way nursing handoff, and only 32% used their EHR to document the transfer process and share clinical information among providers.

Innovations included electronic transfer notes, a standardized system of feedback to referring hospitals, automatic internal review for adverse events and delayed transfers, and use of a scorecard with key measures shared with stakeholders.

Barriers noted included complexity, acuity, and lack of continuity. Increased use of EHRs, checklists, and common processes were identified as best practices.

Limitations of the study included reliance on verbal qualitative data, a single investigator doing most of the discussions, and possible sampling bias.

Bottom line: Interhospital transfer practices at academic tertiary care centers vary widely, and optimizing and aligning practices between sending and receiving hospitals may improve efficiency and patient outcomes.

References: Herrigel DJ, Carroll M, Fanning C, Steinberg MB, Parikh A, Usher M. Interhospital transfer handoff practices among US tertiary care centers: a descriptive survey. J Hosp Med. 2016;11(6):413-417.

Clinical question: How do interhospital handoff practices differ among U.S. tertiary care centers, and what challenges and innovations have providers encountered?

Background: Little has been studied regarding interhospital transfers. Many centers differ in the processes they follow, and well-delineated national guidelines are lacking. Adverse events occur in up to 30% of transfers. Standardization of these handoffs has been shown to reduce preventable errors and near misses.

Study design: Survey of convenience sample of institutions.

Setting: Transfer center directors from 32 tertiary care centers in the U.S.

Synopsis: The authors surveyed directors of 32 transfer centers between 2013 and 2015. Hospitals were selected from a nationally ranked list as well as those comparable to the authors’ own institutions. The median number of patients transferred per month was 700.

Only 23% of hospitals surveyed identified significant EHR interoperability. Almost all required three-way recorded discussion between transfer center staff and referring and accepting physicians. Only 29% had available objective clinical information to share. Only 23% recorded a three-way nursing handoff, and only 32% used their EHR to document the transfer process and share clinical information among providers.

Innovations included electronic transfer notes, a standardized system of feedback to referring hospitals, automatic internal review for adverse events and delayed transfers, and use of a scorecard with key measures shared with stakeholders.

Barriers noted included complexity, acuity, and lack of continuity. Increased use of EHRs, checklists, and common processes were identified as best practices.

Limitations of the study included reliance on verbal qualitative data, a single investigator doing most of the discussions, and possible sampling bias.

Bottom line: Interhospital transfer practices at academic tertiary care centers vary widely, and optimizing and aligning practices between sending and receiving hospitals may improve efficiency and patient outcomes.

References: Herrigel DJ, Carroll M, Fanning C, Steinberg MB, Parikh A, Usher M. Interhospital transfer handoff practices among US tertiary care centers: a descriptive survey. J Hosp Med. 2016;11(6):413-417.

Clinical question: Are oral steroids as effective as NSAIDs in treating acute gout?

Background: Two small trials have suggested that oral steroids are as effective as NSAIDs in treating acute gout. Wider acceptance of steroids as first-line agents for acute gout may require more robust evidence supporting their safety and efficacy.

Study design: Multicenter, double-blind, randomized equivalence trial.

Setting: Four EDs in Hong Kong.

Synopsis: The study included 416 patients presenting to the ED with clinically suspected acute gout who were randomized to treatment with either oral indomethacin or oral prednisolone for five days. A research investigator assessed response to therapy in the ED at 30, 60, 90, and 120 minutes after administration of the initial dose of medication. Patients then kept pain-assessment diaries for 14 days after discharge from the ED.

Pain scores were assessed using a visual analog scale of 0 mm (no pain) to 100 mm (worst pain the patient had experienced). Clinically significant changes in pain scores were defined as decreases of >13 mm on the visual analog scale.

The number of patients with clinically significant decreases in pain scores did not differ statistically between groups. Both groups had similar reductions in mean pain scores over the course of the study. Patients in the indomethacin group had a statistically significant increase in minor adverse events. No patients in either group had major adverse events.

Bottom line: Oral prednisolone appears to be a safe and effective first-line agent for the treatment of acute gout.

Citation: Rainer TH, Chen CH, Janssens HJEM, et al. Oral prednisolone in the treatment of acute gout. Ann Intern Med. 2016;164(7):464-471.

Short Take

Rate Control as Effective as Rhythm Control in Postoperative Atrial Fibrillation

This study randomized patients with postoperative atrial fibrillation to rhythm control (using amiodarone and/or direct current cardioversion) or rate control and found neither treatment strategy has a clinical benefit over the other.

Citation: Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med. 2016;374(20):1911-1921.

Clinical question: Are oral steroids as effective as NSAIDs in treating acute gout?

Background: Two small trials have suggested that oral steroids are as effective as NSAIDs in treating acute gout. Wider acceptance of steroids as first-line agents for acute gout may require more robust evidence supporting their safety and efficacy.

Study design: Multicenter, double-blind, randomized equivalence trial.

Setting: Four EDs in Hong Kong.

Synopsis: The study included 416 patients presenting to the ED with clinically suspected acute gout who were randomized to treatment with either oral indomethacin or oral prednisolone for five days. A research investigator assessed response to therapy in the ED at 30, 60, 90, and 120 minutes after administration of the initial dose of medication. Patients then kept pain-assessment diaries for 14 days after discharge from the ED.

Pain scores were assessed using a visual analog scale of 0 mm (no pain) to 100 mm (worst pain the patient had experienced). Clinically significant changes in pain scores were defined as decreases of >13 mm on the visual analog scale.

The number of patients with clinically significant decreases in pain scores did not differ statistically between groups. Both groups had similar reductions in mean pain scores over the course of the study. Patients in the indomethacin group had a statistically significant increase in minor adverse events. No patients in either group had major adverse events.

Bottom line: Oral prednisolone appears to be a safe and effective first-line agent for the treatment of acute gout.

Citation: Rainer TH, Chen CH, Janssens HJEM, et al. Oral prednisolone in the treatment of acute gout. Ann Intern Med. 2016;164(7):464-471.

Short Take

Rate Control as Effective as Rhythm Control in Postoperative Atrial Fibrillation

This study randomized patients with postoperative atrial fibrillation to rhythm control (using amiodarone and/or direct current cardioversion) or rate control and found neither treatment strategy has a clinical benefit over the other.

Citation: Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med. 2016;374(20):1911-1921.

Clinical question: Are oral steroids as effective as NSAIDs in treating acute gout?

Background: Two small trials have suggested that oral steroids are as effective as NSAIDs in treating acute gout. Wider acceptance of steroids as first-line agents for acute gout may require more robust evidence supporting their safety and efficacy.

Study design: Multicenter, double-blind, randomized equivalence trial.

Setting: Four EDs in Hong Kong.

Synopsis: The study included 416 patients presenting to the ED with clinically suspected acute gout who were randomized to treatment with either oral indomethacin or oral prednisolone for five days. A research investigator assessed response to therapy in the ED at 30, 60, 90, and 120 minutes after administration of the initial dose of medication. Patients then kept pain-assessment diaries for 14 days after discharge from the ED.

Pain scores were assessed using a visual analog scale of 0 mm (no pain) to 100 mm (worst pain the patient had experienced). Clinically significant changes in pain scores were defined as decreases of >13 mm on the visual analog scale.

The number of patients with clinically significant decreases in pain scores did not differ statistically between groups. Both groups had similar reductions in mean pain scores over the course of the study. Patients in the indomethacin group had a statistically significant increase in minor adverse events. No patients in either group had major adverse events.

Bottom line: Oral prednisolone appears to be a safe and effective first-line agent for the treatment of acute gout.

Citation: Rainer TH, Chen CH, Janssens HJEM, et al. Oral prednisolone in the treatment of acute gout. Ann Intern Med. 2016;164(7):464-471.

Short Take

Rate Control as Effective as Rhythm Control in Postoperative Atrial Fibrillation

This study randomized patients with postoperative atrial fibrillation to rhythm control (using amiodarone and/or direct current cardioversion) or rate control and found neither treatment strategy has a clinical benefit over the other.

Citation: Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med. 2016;374(20):1911-1921.