Mona Krouss, MD

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason^™” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 56-year-old woman presents to the emergency department with a 2-week history of abdominal pain associated with nausea and an episode of nonbilious, nonbloody emesis. Her last bowel movement was 2 days prior to her presentation. The patient has tachycardia to 105 beats per minute but otherwise normal vital signs. Findings on her physical examination include dry mucous membranes and increased bowel sounds. A review of systems reveals an unintentional weight loss of 15 kg over the past 4 months and increased fatigue. Computed tomography scan of the abdomen and pelvis with contrast reveals multiple areas of attenuation in the liver and small bowel obstruction. The hospitalist admits the patient to the medicine service for supportive treatment and workup for underlying malignancy. Her admitting team orders serum tumor biomarkers on admission to expedite the diagnosis.

When patients present with unexplained weight loss or with metastasis from an unknown primary location, the initial workup often includes imaging and a tumor biomarker panel (eg, cancer antigen 125 [CA125], carbohydrate antigen 19-9 [CA19-9], carcinoembryonic antigen [CEA]). The CA125, CA19-9, and CEA biomarkers are traditionally associated with ovarian, pancreatic, and colorectal cancer, respectively.¹ While clinicians initially used these serum biomarkers to monitor for cancer recurrence or treatment response, they have since become widely used in multiple clinical stages of oncological evaluation.

Hospitalists routinely order biomarkers as part of the malignancy workup. More than a dozen oncology biomarkers are used in the clinical setting to risk stratify, plan treatment, and monitor for recurrence. For example, studies associate elevated preoperative levels of CEA and CA19-9 with metastatic invasion of colorectal² and gastric³ cancers and with poor prognosis of intrahepatic cholangiocarcinoma. Similarly, CA125 has demonstrated utility in monitoring response to ovarian cancer treatment.⁴ Specific biomarkers, such as alpha-fetoprotein, improve diagnosis of liver and nonseminomatous testicular tumors.⁵ Clinicians often apply the same paradigm to other biomarkers due to their widespread availability, noninvasiveness, reproducibility, and ease of use, particularly in acute settings wherein any new information is perceived to be potentially helpful.

Utilizing these serum biomarkers to diagnose cancer has the potential for diagnostic error and can result in unnecessary patient anxiety and follow-up testing. Since tissue sampling is necessary and remains the gold standard in most cancer diagnoses, obtaining these tumor biomarkers in the early diagnostic stage does not change management and may even lead to harm. Furthermore, due to their poor sensitivity and specificity, these biomarkers cannot rule in or rule out cancer. Elevated CA125, CA19-9, and CEA biomarkers occur in a variety of malignancies, including gastric, gallbladder, hepatocellular, bladder, and breast cancers.^1,3,6 In addition, these biomarkers have a very limited role in the workup of cancer of unknown primary origin.⁷

Even in the setting of a known pelvic mass, the use of CA125 alone has poor sensitivity at a cut-off level of 35 U/mL as a biomarker for the diagnosis of early ovarian cancer.⁸

Serum CA19-9 is not a useful diagnostic biomarker as elevated CA19-9 can occur in benign conditions, including cirrhosis, chronic pancreatitis, and cholangitis. In a systematic review of patients with histologic confirmation of pancreatic malignancy, the median positive predictive value of CA19-9 was 72% (interquartile range, 41%-95%).⁹ Additionally, patients with Lewis-null blood type, which is present in 5% to 10% of the Caucasian population, do not produce CA19-9.¹⁰ Therefore, CA19-9 will be 0% specific for tumors in this population.

The use of CEA in the diagnosis of colorectal cancer is also questionable. In stage I colorectal cancer, CEA was only 38.1% sensitive at a cut-off level of 2.41 ng/mL; it was 78.3% sensitive in stage IV disease.¹¹ The specificity of CEA is limited since elevated CEA occurs in benign conditions, such as inflammatory bowel disease, smoking, hypothyroidism, pancreatitis, biliary obstruction, peptic ulcers, and cirrhosis—though CEA levels in these conditions are rarely >10 ng/mL.¹¹ Regardless of the results of biomarker testing, definitive diagnosis requires tissue biopsy; therefore, biomarker findings are of little utility in the initial workup.

In addition to variable diagnostic utility, overreliance on these biomarkers has the potential for serious patient harm. In a study examining patients with established rectal cancer, combination CEA and CA19-9 testing alone was insufficient to predict the pathologic stage of disease correctly.² A cancer misdiagnosis not only traumatizes patients but also erodes their trust in clinicians and creates anxiety during future clinical encounters. Overutilization of these tumor biomarkers is also costly and contributes to waste in the US healthcare system.

There is a role for tumor biomarker testing in specific cancers after the primary source of malignancy has been determined. When evaluating a known pelvic mass, CA125 testing is performed in conjunction with transvaginal ultrasound and assessment of menopausal status in the risk of ovarian malignancy algorithm for prognostication of disease prior to surgery.¹² This algorithm takes into account levels of CA125 in addition to levels of human epididymis protein 4 and patient age, yielding an area under the curve as high as 0.93 for ovarian cancer risk classification.⁸ Beyond the prognostication process, oncologists follow CA125 to monitor response to first-line ovarian cancer treatment. However, CA125 has a less defined role in surveillance for ovarian cancer recurrence.

CA19-9 has demonstrated utility for pancreatic cancer and cholangiocarcinoma survival estimates. A national cohort analysis of patients with established intrahepatic cholangiocarcinoma found that CA19-9 independently predicted increased mortality. Patients with elevated CA19-9 also had significantly more nodal metastases and positive-margin resections.⁶ A study of 353 patients with pancreatic ductal adenocarcinoma undergoing radical resection further demonstrated the utility of CA19-9. In this study, patients with postoperative CA19-9 normalization had improved survival by almost 12 months when compared to those with consistently elevated CA19-9.¹³

Last, the literature describes CEA biomarker testing in the surveillance of patients after curative treatment of colon and rectal cancer. The American Society of Colon and Rectal Surgeons recommends regularly tracking this biomarker following curative resection, in conjunction with colonoscopy and chest and liver imaging studies.¹⁴ A prospective randomized controlled study that followed this monitoring protocol in cured asymptomatic patients on a bimonthly basis found that early diagnosis of recurrent colorectal cancer improved survival.¹⁵ The use of CEA testing as a monitoring tool should therefore be a point of discussion between providers and patients, as its utility varies based on patient comorbidities, their ability to tolerate surgery or chemotherapy, risk factors for recurrence, performance status, compliance, age, and preference.¹⁴

The use of CA125, CA19-9, and CEA testing alone as initial diagnostic tools for malignancy are problematic due to their poor sensitivities and/or positive predictive value. Multiple studies have demonstrated their utility as markers of metastasis or malignancy progression rather than as clinically useful markers for the detection of any one type of cancer.^1,3,6 In an undiagnosed symptomatic patient with unexplained weight loss or symptoms of a tumor mass, elevated CA125, CA19-9, and CEA add no new information as metastatic pancreatic, colorectal, ovarian, gastric, gallbladder, hepatocellular, bladder, ovarian, and breast cancers all remain in the differential diagnosis. Clinicians should approach the initial diagnosis of cancer in such patients with appropriate imaging studies, a thorough physical examination, and prompt biopsy of abnormal findings, as long as these are consistent with the patient’s goals of care. After establishing a tissue diagnosis, some tumor biomarkers have valid prognostic, staging, and monitoring roles.^6,13,14

• Do not routinely order CA125, CA19-9, and CEA tests for the initial diagnostic workup of visceral malignancy of unknown origin regardless of whether imaging studies have been obtained.
• Use appropriate imaging, perform a thorough physical examination, and obtain tissue biopsy in the initial diagnostic workup of a visceral malignancy of unknown origin.

Clinicians should use serum biomarkers, like any other diagnostic test, to maximize benefit while preventing patient harm. In general, CA125, CA19-9, and CEA do not have a role in cancer diagnosis. The patient described in our clinical scenario would not benefit from a serum tumor biomarker panel at the time of admission. Regardless of findings from these tests, a tissue sample is required to make a definitive diagnosis of underlying malignancy in this patient.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason^™”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason^™” topics by emailing [email protected]

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason^™” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 56-year-old woman presents to the emergency department with a 2-week history of abdominal pain associated with nausea and an episode of nonbilious, nonbloody emesis. Her last bowel movement was 2 days prior to her presentation. The patient has tachycardia to 105 beats per minute but otherwise normal vital signs. Findings on her physical examination include dry mucous membranes and increased bowel sounds. A review of systems reveals an unintentional weight loss of 15 kg over the past 4 months and increased fatigue. Computed tomography scan of the abdomen and pelvis with contrast reveals multiple areas of attenuation in the liver and small bowel obstruction. The hospitalist admits the patient to the medicine service for supportive treatment and workup for underlying malignancy. Her admitting team orders serum tumor biomarkers on admission to expedite the diagnosis.

When patients present with unexplained weight loss or with metastasis from an unknown primary location, the initial workup often includes imaging and a tumor biomarker panel (eg, cancer antigen 125 [CA125], carbohydrate antigen 19-9 [CA19-9], carcinoembryonic antigen [CEA]). The CA125, CA19-9, and CEA biomarkers are traditionally associated with ovarian, pancreatic, and colorectal cancer, respectively.¹ While clinicians initially used these serum biomarkers to monitor for cancer recurrence or treatment response, they have since become widely used in multiple clinical stages of oncological evaluation.

Hospitalists routinely order biomarkers as part of the malignancy workup. More than a dozen oncology biomarkers are used in the clinical setting to risk stratify, plan treatment, and monitor for recurrence. For example, studies associate elevated preoperative levels of CEA and CA19-9 with metastatic invasion of colorectal² and gastric³ cancers and with poor prognosis of intrahepatic cholangiocarcinoma. Similarly, CA125 has demonstrated utility in monitoring response to ovarian cancer treatment.⁴ Specific biomarkers, such as alpha-fetoprotein, improve diagnosis of liver and nonseminomatous testicular tumors.⁵ Clinicians often apply the same paradigm to other biomarkers due to their widespread availability, noninvasiveness, reproducibility, and ease of use, particularly in acute settings wherein any new information is perceived to be potentially helpful.

Utilizing these serum biomarkers to diagnose cancer has the potential for diagnostic error and can result in unnecessary patient anxiety and follow-up testing. Since tissue sampling is necessary and remains the gold standard in most cancer diagnoses, obtaining these tumor biomarkers in the early diagnostic stage does not change management and may even lead to harm. Furthermore, due to their poor sensitivity and specificity, these biomarkers cannot rule in or rule out cancer. Elevated CA125, CA19-9, and CEA biomarkers occur in a variety of malignancies, including gastric, gallbladder, hepatocellular, bladder, and breast cancers.^1,3,6 In addition, these biomarkers have a very limited role in the workup of cancer of unknown primary origin.⁷

Even in the setting of a known pelvic mass, the use of CA125 alone has poor sensitivity at a cut-off level of 35 U/mL as a biomarker for the diagnosis of early ovarian cancer.⁸

Serum CA19-9 is not a useful diagnostic biomarker as elevated CA19-9 can occur in benign conditions, including cirrhosis, chronic pancreatitis, and cholangitis. In a systematic review of patients with histologic confirmation of pancreatic malignancy, the median positive predictive value of CA19-9 was 72% (interquartile range, 41%-95%).⁹ Additionally, patients with Lewis-null blood type, which is present in 5% to 10% of the Caucasian population, do not produce CA19-9.¹⁰ Therefore, CA19-9 will be 0% specific for tumors in this population.

The use of CEA in the diagnosis of colorectal cancer is also questionable. In stage I colorectal cancer, CEA was only 38.1% sensitive at a cut-off level of 2.41 ng/mL; it was 78.3% sensitive in stage IV disease.¹¹ The specificity of CEA is limited since elevated CEA occurs in benign conditions, such as inflammatory bowel disease, smoking, hypothyroidism, pancreatitis, biliary obstruction, peptic ulcers, and cirrhosis—though CEA levels in these conditions are rarely >10 ng/mL.¹¹ Regardless of the results of biomarker testing, definitive diagnosis requires tissue biopsy; therefore, biomarker findings are of little utility in the initial workup.

In addition to variable diagnostic utility, overreliance on these biomarkers has the potential for serious patient harm. In a study examining patients with established rectal cancer, combination CEA and CA19-9 testing alone was insufficient to predict the pathologic stage of disease correctly.² A cancer misdiagnosis not only traumatizes patients but also erodes their trust in clinicians and creates anxiety during future clinical encounters. Overutilization of these tumor biomarkers is also costly and contributes to waste in the US healthcare system.

There is a role for tumor biomarker testing in specific cancers after the primary source of malignancy has been determined. When evaluating a known pelvic mass, CA125 testing is performed in conjunction with transvaginal ultrasound and assessment of menopausal status in the risk of ovarian malignancy algorithm for prognostication of disease prior to surgery.¹² This algorithm takes into account levels of CA125 in addition to levels of human epididymis protein 4 and patient age, yielding an area under the curve as high as 0.93 for ovarian cancer risk classification.⁸ Beyond the prognostication process, oncologists follow CA125 to monitor response to first-line ovarian cancer treatment. However, CA125 has a less defined role in surveillance for ovarian cancer recurrence.

CA19-9 has demonstrated utility for pancreatic cancer and cholangiocarcinoma survival estimates. A national cohort analysis of patients with established intrahepatic cholangiocarcinoma found that CA19-9 independently predicted increased mortality. Patients with elevated CA19-9 also had significantly more nodal metastases and positive-margin resections.⁶ A study of 353 patients with pancreatic ductal adenocarcinoma undergoing radical resection further demonstrated the utility of CA19-9. In this study, patients with postoperative CA19-9 normalization had improved survival by almost 12 months when compared to those with consistently elevated CA19-9.¹³

Last, the literature describes CEA biomarker testing in the surveillance of patients after curative treatment of colon and rectal cancer. The American Society of Colon and Rectal Surgeons recommends regularly tracking this biomarker following curative resection, in conjunction with colonoscopy and chest and liver imaging studies.¹⁴ A prospective randomized controlled study that followed this monitoring protocol in cured asymptomatic patients on a bimonthly basis found that early diagnosis of recurrent colorectal cancer improved survival.¹⁵ The use of CEA testing as a monitoring tool should therefore be a point of discussion between providers and patients, as its utility varies based on patient comorbidities, their ability to tolerate surgery or chemotherapy, risk factors for recurrence, performance status, compliance, age, and preference.¹⁴

The use of CA125, CA19-9, and CEA testing alone as initial diagnostic tools for malignancy are problematic due to their poor sensitivities and/or positive predictive value. Multiple studies have demonstrated their utility as markers of metastasis or malignancy progression rather than as clinically useful markers for the detection of any one type of cancer.^1,3,6 In an undiagnosed symptomatic patient with unexplained weight loss or symptoms of a tumor mass, elevated CA125, CA19-9, and CEA add no new information as metastatic pancreatic, colorectal, ovarian, gastric, gallbladder, hepatocellular, bladder, ovarian, and breast cancers all remain in the differential diagnosis. Clinicians should approach the initial diagnosis of cancer in such patients with appropriate imaging studies, a thorough physical examination, and prompt biopsy of abnormal findings, as long as these are consistent with the patient’s goals of care. After establishing a tissue diagnosis, some tumor biomarkers have valid prognostic, staging, and monitoring roles.^6,13,14

• Do not routinely order CA125, CA19-9, and CEA tests for the initial diagnostic workup of visceral malignancy of unknown origin regardless of whether imaging studies have been obtained.
• Use appropriate imaging, perform a thorough physical examination, and obtain tissue biopsy in the initial diagnostic workup of a visceral malignancy of unknown origin.

Clinicians should use serum biomarkers, like any other diagnostic test, to maximize benefit while preventing patient harm. In general, CA125, CA19-9, and CEA do not have a role in cancer diagnosis. The patient described in our clinical scenario would not benefit from a serum tumor biomarker panel at the time of admission. Regardless of findings from these tests, a tissue sample is required to make a definitive diagnosis of underlying malignancy in this patient.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason^™”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason^™” topics by emailing [email protected]

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason^™” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 56-year-old woman presents to the emergency department with a 2-week history of abdominal pain associated with nausea and an episode of nonbilious, nonbloody emesis. Her last bowel movement was 2 days prior to her presentation. The patient has tachycardia to 105 beats per minute but otherwise normal vital signs. Findings on her physical examination include dry mucous membranes and increased bowel sounds. A review of systems reveals an unintentional weight loss of 15 kg over the past 4 months and increased fatigue. Computed tomography scan of the abdomen and pelvis with contrast reveals multiple areas of attenuation in the liver and small bowel obstruction. The hospitalist admits the patient to the medicine service for supportive treatment and workup for underlying malignancy. Her admitting team orders serum tumor biomarkers on admission to expedite the diagnosis.

When patients present with unexplained weight loss or with metastasis from an unknown primary location, the initial workup often includes imaging and a tumor biomarker panel (eg, cancer antigen 125 [CA125], carbohydrate antigen 19-9 [CA19-9], carcinoembryonic antigen [CEA]). The CA125, CA19-9, and CEA biomarkers are traditionally associated with ovarian, pancreatic, and colorectal cancer, respectively.¹ While clinicians initially used these serum biomarkers to monitor for cancer recurrence or treatment response, they have since become widely used in multiple clinical stages of oncological evaluation.

Hospitalists routinely order biomarkers as part of the malignancy workup. More than a dozen oncology biomarkers are used in the clinical setting to risk stratify, plan treatment, and monitor for recurrence. For example, studies associate elevated preoperative levels of CEA and CA19-9 with metastatic invasion of colorectal² and gastric³ cancers and with poor prognosis of intrahepatic cholangiocarcinoma. Similarly, CA125 has demonstrated utility in monitoring response to ovarian cancer treatment.⁴ Specific biomarkers, such as alpha-fetoprotein, improve diagnosis of liver and nonseminomatous testicular tumors.⁵ Clinicians often apply the same paradigm to other biomarkers due to their widespread availability, noninvasiveness, reproducibility, and ease of use, particularly in acute settings wherein any new information is perceived to be potentially helpful.

Utilizing these serum biomarkers to diagnose cancer has the potential for diagnostic error and can result in unnecessary patient anxiety and follow-up testing. Since tissue sampling is necessary and remains the gold standard in most cancer diagnoses, obtaining these tumor biomarkers in the early diagnostic stage does not change management and may even lead to harm. Furthermore, due to their poor sensitivity and specificity, these biomarkers cannot rule in or rule out cancer. Elevated CA125, CA19-9, and CEA biomarkers occur in a variety of malignancies, including gastric, gallbladder, hepatocellular, bladder, and breast cancers.^1,3,6 In addition, these biomarkers have a very limited role in the workup of cancer of unknown primary origin.⁷

Even in the setting of a known pelvic mass, the use of CA125 alone has poor sensitivity at a cut-off level of 35 U/mL as a biomarker for the diagnosis of early ovarian cancer.⁸

Serum CA19-9 is not a useful diagnostic biomarker as elevated CA19-9 can occur in benign conditions, including cirrhosis, chronic pancreatitis, and cholangitis. In a systematic review of patients with histologic confirmation of pancreatic malignancy, the median positive predictive value of CA19-9 was 72% (interquartile range, 41%-95%).⁹ Additionally, patients with Lewis-null blood type, which is present in 5% to 10% of the Caucasian population, do not produce CA19-9.¹⁰ Therefore, CA19-9 will be 0% specific for tumors in this population.

The use of CEA in the diagnosis of colorectal cancer is also questionable. In stage I colorectal cancer, CEA was only 38.1% sensitive at a cut-off level of 2.41 ng/mL; it was 78.3% sensitive in stage IV disease.¹¹ The specificity of CEA is limited since elevated CEA occurs in benign conditions, such as inflammatory bowel disease, smoking, hypothyroidism, pancreatitis, biliary obstruction, peptic ulcers, and cirrhosis—though CEA levels in these conditions are rarely >10 ng/mL.¹¹ Regardless of the results of biomarker testing, definitive diagnosis requires tissue biopsy; therefore, biomarker findings are of little utility in the initial workup.

In addition to variable diagnostic utility, overreliance on these biomarkers has the potential for serious patient harm. In a study examining patients with established rectal cancer, combination CEA and CA19-9 testing alone was insufficient to predict the pathologic stage of disease correctly.² A cancer misdiagnosis not only traumatizes patients but also erodes their trust in clinicians and creates anxiety during future clinical encounters. Overutilization of these tumor biomarkers is also costly and contributes to waste in the US healthcare system.

There is a role for tumor biomarker testing in specific cancers after the primary source of malignancy has been determined. When evaluating a known pelvic mass, CA125 testing is performed in conjunction with transvaginal ultrasound and assessment of menopausal status in the risk of ovarian malignancy algorithm for prognostication of disease prior to surgery.¹² This algorithm takes into account levels of CA125 in addition to levels of human epididymis protein 4 and patient age, yielding an area under the curve as high as 0.93 for ovarian cancer risk classification.⁸ Beyond the prognostication process, oncologists follow CA125 to monitor response to first-line ovarian cancer treatment. However, CA125 has a less defined role in surveillance for ovarian cancer recurrence.

CA19-9 has demonstrated utility for pancreatic cancer and cholangiocarcinoma survival estimates. A national cohort analysis of patients with established intrahepatic cholangiocarcinoma found that CA19-9 independently predicted increased mortality. Patients with elevated CA19-9 also had significantly more nodal metastases and positive-margin resections.⁶ A study of 353 patients with pancreatic ductal adenocarcinoma undergoing radical resection further demonstrated the utility of CA19-9. In this study, patients with postoperative CA19-9 normalization had improved survival by almost 12 months when compared to those with consistently elevated CA19-9.¹³

Last, the literature describes CEA biomarker testing in the surveillance of patients after curative treatment of colon and rectal cancer. The American Society of Colon and Rectal Surgeons recommends regularly tracking this biomarker following curative resection, in conjunction with colonoscopy and chest and liver imaging studies.¹⁴ A prospective randomized controlled study that followed this monitoring protocol in cured asymptomatic patients on a bimonthly basis found that early diagnosis of recurrent colorectal cancer improved survival.¹⁵ The use of CEA testing as a monitoring tool should therefore be a point of discussion between providers and patients, as its utility varies based on patient comorbidities, their ability to tolerate surgery or chemotherapy, risk factors for recurrence, performance status, compliance, age, and preference.¹⁴

The use of CA125, CA19-9, and CEA testing alone as initial diagnostic tools for malignancy are problematic due to their poor sensitivities and/or positive predictive value. Multiple studies have demonstrated their utility as markers of metastasis or malignancy progression rather than as clinically useful markers for the detection of any one type of cancer.^1,3,6 In an undiagnosed symptomatic patient with unexplained weight loss or symptoms of a tumor mass, elevated CA125, CA19-9, and CEA add no new information as metastatic pancreatic, colorectal, ovarian, gastric, gallbladder, hepatocellular, bladder, ovarian, and breast cancers all remain in the differential diagnosis. Clinicians should approach the initial diagnosis of cancer in such patients with appropriate imaging studies, a thorough physical examination, and prompt biopsy of abnormal findings, as long as these are consistent with the patient’s goals of care. After establishing a tissue diagnosis, some tumor biomarkers have valid prognostic, staging, and monitoring roles.^6,13,14

• Do not routinely order CA125, CA19-9, and CEA tests for the initial diagnostic workup of visceral malignancy of unknown origin regardless of whether imaging studies have been obtained.
• Use appropriate imaging, perform a thorough physical examination, and obtain tissue biopsy in the initial diagnostic workup of a visceral malignancy of unknown origin.

Clinicians should use serum biomarkers, like any other diagnostic test, to maximize benefit while preventing patient harm. In general, CA125, CA19-9, and CEA do not have a role in cancer diagnosis. The patient described in our clinical scenario would not benefit from a serum tumor biomarker panel at the time of admission. Regardless of findings from these tests, a tissue sample is required to make a definitive diagnosis of underlying malignancy in this patient.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason^™”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason^™” topics by emailing [email protected]

With more than 3 million people diagnosed and more than 200,000 deaths worldwide at the time this article was written, coronavirus disease of 2019 (COVID-19) poses an unprecedented challenge to the public and to our healthcare system.¹ The United States has surpassed every other country in the total number of COVID-19 cases. Hospitals in hotspots are operating beyond capacity, while others prepare for a predicted surge of patients suffering from COVID-19. Now more than ever, clinicians need to prioritize limited time and resources wisely in this rapidly changing environment. Our most precious limited resource, healthcare workers (HCWs), bravely care for patients while trying to avoid acquiring the infection. With each test and treatment, clinicians must carefully consider harms and benefits, including exposing themselves and other HCWs to SARS-CoV-2, the virus causing this disease.

Delivering any healthcare service in which the potential harm exceeds benefit represents one form of overuse. In the era of COVID-19, the harmful consequences of overuse go beyond the patient to the healthcare team. For example, unnecessary chest computed tomography (CT) to help diagnose COVID-19 comes with the usual risks to the patient including radiation, but it may also reveal a suspicious nodule. That incidental finding can lead to downstream consequences, such as more imaging, blood work, and biopsy. In the current pandemic, however, that CT comes with more than just the usual risk. The initial unnecessary chest CT can risk exposing the transporter, the staff in the hallways and elevator en route, the radiology staff operating the CT scanner, and the maintenance staff who must clean the room and scanner afterward. Potential downstream harms to staff include exposure of the pulmonary and interventional radiology consultants, as well as the staff who perform repeat imaging after the biopsy. Evaluation of the nodule potentially prolongs the patient’s stay and exposes more staff. Clinicians must weigh the benefits and harms of each test and treatment carefully with consideration of both the patient and the staff involved. Moreover, it may turn out that the patient and staff without symptoms of COVID-19 may pose the most risk to one another.

Choosing Wisely® partnered with patients and clinician societies to develop a Top 5 recommendations list for eliminating unnecessary testing and treatment. Our multi-institutional group from the High Value Practice Academic Alliance proposed this Top 5 list of overuse practices in hospital medicine that can lead to harm of both patients and HCWs in the COVID-19 era (Table). The following recommendations apply to all patients with unsuspected, suspected, or confirmed SARS-CoV-2 infection in the hospital setting.

• Do not obtain nonurgent labs in separate blood draws if they can be batched together.

This recommendation expands on the original Society of Hospital Medicine Choosing Wisely recommendation: Don’t perform repetitive complete blood count and chemistry testing in the face of clinical and lab stability.² Aside from patient harms such as pain and hospital-acquired anemia, the risk of exposure to HCWs who perform phlebotomy (phlebotomists, nurses, and other clinicians), as well as staff who transport, handle, and process the bloodwork in the lab, must be minimized. Most prior interventions to eliminate unnecessary bloodwork focused on the number of lab tests,³ but some also aimed to batch nonurgent labs together to effectively reduce unnecessary needlesticks (“think twice, stick once”).⁴ This concept can be brought into this pandemic to provide safe and appropriate care for both patients and HCWs.

• Do not use bronchodilators unless there is active obstructive airway disease, and if needed, use metered dose inhalers instead of nebulizers.

We do not recommend using bronchodilators to treat COVID-19 symptoms unless patients develop acute bronchospastic symptoms of their underlying obstructive airway disease.⁵ When needed, use metered dose inhalers (MDIs),⁶ if available, instead of nebulizers because the latter potentiates aerosolization that could lead to higher risk of spreading the infection. The risk extends to respiratory technicians and nurses who administer the nebulizer, as well as other HCWs who enter the room during or after administration. The Centers for Disease Control and Prevention (CDC) considers nebulized bronchodilator therapy a “high-risk” exposure for HCWs not wearing the proper personal protectvie equipment.⁷ Moreover, MDI therapy produces equivalent outcomes to nebulized treatments for patients who are not critically ill.⁶ Unfortunately, the supply of MDIs during this crisis has not kept up with the increased demand.⁸

There are no clear guidelines for reuse of MDIs in COVID-19; however, options include labeling patients’ MDIs to use for hospitalization and discharge or labeling an MDI for use during hospitalization and then disinfecting for reuse. For safety reasons, MDIs of COVID-19 patients should be reused only for other patients with COVID-19.⁸

• Do not use posteroanterior and lateral chest X-ray as initial imaging. Use a portable chest X-ray instead.

The CDC does not currently recommend diagnosing COVID-19 by chest X-ray (CXR).⁷ When used appropriately, CXR can provide information to support a COVID-19 diagnosis and rule out other etiologies that cause respiratory symptoms.⁹ Posteroanterior (PA) and lateral CXR are more sensitive than portable CXR for detecting pleural effusions, and lateral CXR is needed to examine structures along the axis of the body. Portable CXR also may cause the heart to appear magnified and the mediastinum widened, the diaphragm to appear higher, and vascular shadows to be obscured.¹⁰ The improved ability to detect these subtle differences should be weighed against the increased risk to HCWs required to perform PA and lateral CXR. A portable CXR exposes a relatively smaller number of staff who come to the bedside versus the larger number of people exposed in transporting the patient out of the room and into the hallway, elevator, and the radiology suite for a PA and lateral CXR.

• Avoid in-person evaluations in favor of virtual communication unless necessary.

To minimize HCW exposure to COVID-19 and optimize infection control, the CDC recommends the use of telemedicine when possible.⁷ Telemedicine refers to the use of technology to support clinical care across some distance, which includes video visits and remote clinical monitoring. At the time of writing, the Centers for Medicare & Medicaid Services had waived the rural site of care requirement for Medicare beneficiaries, granted 49 Medicaid waivers to states to enhance flexibility, and (at least temporarily) added inpatient care to the list of reimbursed telemedicine services.¹¹ Funding for expanded coverage under Medicare is included in the recent Coronavirus Preparedness and Response Supplemental Appropriations Act.¹² These federal changes open the door for commercial payers and state Medicaid programs to further boost telemedicine through reimbursement parity to in-person visits and other coverage policies. Hospitalists can ride this momentum and learn from ambulatory colleagues to harness the power of telemedicine and minimize unnecessary face-to-face interactions with patients who are suspected or confirmed to have COVID-19.¹³ Even if providers have to enter the patient’s room, telemedicine may still allow for large virtual family meetings despite strict visitor restrictions and physical distance with loved ones. If in-person visits are necessary, only one designated person should enter the patient’s room instead of the entire team.

• Do not delay goals of care conversations for hospitalized patients who are unlikely to benefit from life-sustaining treatments.

The COVID-19 pandemic amplifies the need for early goals of care discussions. Mortality rates range higher with acute respiratory distress syndrome from COVID-19, compared with other etiologies, and is associated with extended intensive care unit stays.¹⁴ The harms extend beyond the patient and families to our HCWs through psychological distress and heightened exposure from aerosolization during resuscitation. Advance care planning should center on the values and preferences of the patient. Rather than asking if the patient or family would want certain treatments, it is crucial for clinicians to be direct in making do-not-resuscitate recommendations if deemed futile care.¹⁵ This practice is well within legal confines and is distinct from withdrawal or withholding of life-sustaining resources.¹⁵

HCWs providing inpatient care during this pandemic remain among the highest risk for contracting the infection. As of April 9, 2020, nearly 9,300 HCWs in the United States have contracted COVID-19.¹⁶ One thing remains clear: If we want to protect our patients, we must start by protecting our HCWs. We must think critically to evaluate the potential harms to our extended healthcare teams and strive further to eliminate overuse from our care.

The authors represent members of the High Value Practice Academic Alliance. The High Value Practice Academic Alliance is a consortium of academic medical centers in the United States and Canada working to advance high-value healthcare through collaborative quality improvement, research, and education. Additional information is available at http://www.hvpaa.org.

With more than 3 million people diagnosed and more than 200,000 deaths worldwide at the time this article was written, coronavirus disease of 2019 (COVID-19) poses an unprecedented challenge to the public and to our healthcare system.¹ The United States has surpassed every other country in the total number of COVID-19 cases. Hospitals in hotspots are operating beyond capacity, while others prepare for a predicted surge of patients suffering from COVID-19. Now more than ever, clinicians need to prioritize limited time and resources wisely in this rapidly changing environment. Our most precious limited resource, healthcare workers (HCWs), bravely care for patients while trying to avoid acquiring the infection. With each test and treatment, clinicians must carefully consider harms and benefits, including exposing themselves and other HCWs to SARS-CoV-2, the virus causing this disease.

Delivering any healthcare service in which the potential harm exceeds benefit represents one form of overuse. In the era of COVID-19, the harmful consequences of overuse go beyond the patient to the healthcare team. For example, unnecessary chest computed tomography (CT) to help diagnose COVID-19 comes with the usual risks to the patient including radiation, but it may also reveal a suspicious nodule. That incidental finding can lead to downstream consequences, such as more imaging, blood work, and biopsy. In the current pandemic, however, that CT comes with more than just the usual risk. The initial unnecessary chest CT can risk exposing the transporter, the staff in the hallways and elevator en route, the radiology staff operating the CT scanner, and the maintenance staff who must clean the room and scanner afterward. Potential downstream harms to staff include exposure of the pulmonary and interventional radiology consultants, as well as the staff who perform repeat imaging after the biopsy. Evaluation of the nodule potentially prolongs the patient’s stay and exposes more staff. Clinicians must weigh the benefits and harms of each test and treatment carefully with consideration of both the patient and the staff involved. Moreover, it may turn out that the patient and staff without symptoms of COVID-19 may pose the most risk to one another.

Choosing Wisely® partnered with patients and clinician societies to develop a Top 5 recommendations list for eliminating unnecessary testing and treatment. Our multi-institutional group from the High Value Practice Academic Alliance proposed this Top 5 list of overuse practices in hospital medicine that can lead to harm of both patients and HCWs in the COVID-19 era (Table). The following recommendations apply to all patients with unsuspected, suspected, or confirmed SARS-CoV-2 infection in the hospital setting.

• Do not obtain nonurgent labs in separate blood draws if they can be batched together.

This recommendation expands on the original Society of Hospital Medicine Choosing Wisely recommendation: Don’t perform repetitive complete blood count and chemistry testing in the face of clinical and lab stability.² Aside from patient harms such as pain and hospital-acquired anemia, the risk of exposure to HCWs who perform phlebotomy (phlebotomists, nurses, and other clinicians), as well as staff who transport, handle, and process the bloodwork in the lab, must be minimized. Most prior interventions to eliminate unnecessary bloodwork focused on the number of lab tests,³ but some also aimed to batch nonurgent labs together to effectively reduce unnecessary needlesticks (“think twice, stick once”).⁴ This concept can be brought into this pandemic to provide safe and appropriate care for both patients and HCWs.

• Do not use bronchodilators unless there is active obstructive airway disease, and if needed, use metered dose inhalers instead of nebulizers.

We do not recommend using bronchodilators to treat COVID-19 symptoms unless patients develop acute bronchospastic symptoms of their underlying obstructive airway disease.⁵ When needed, use metered dose inhalers (MDIs),⁶ if available, instead of nebulizers because the latter potentiates aerosolization that could lead to higher risk of spreading the infection. The risk extends to respiratory technicians and nurses who administer the nebulizer, as well as other HCWs who enter the room during or after administration. The Centers for Disease Control and Prevention (CDC) considers nebulized bronchodilator therapy a “high-risk” exposure for HCWs not wearing the proper personal protectvie equipment.⁷ Moreover, MDI therapy produces equivalent outcomes to nebulized treatments for patients who are not critically ill.⁶ Unfortunately, the supply of MDIs during this crisis has not kept up with the increased demand.⁸

There are no clear guidelines for reuse of MDIs in COVID-19; however, options include labeling patients’ MDIs to use for hospitalization and discharge or labeling an MDI for use during hospitalization and then disinfecting for reuse. For safety reasons, MDIs of COVID-19 patients should be reused only for other patients with COVID-19.⁸

• Do not use posteroanterior and lateral chest X-ray as initial imaging. Use a portable chest X-ray instead.

The CDC does not currently recommend diagnosing COVID-19 by chest X-ray (CXR).⁷ When used appropriately, CXR can provide information to support a COVID-19 diagnosis and rule out other etiologies that cause respiratory symptoms.⁹ Posteroanterior (PA) and lateral CXR are more sensitive than portable CXR for detecting pleural effusions, and lateral CXR is needed to examine structures along the axis of the body. Portable CXR also may cause the heart to appear magnified and the mediastinum widened, the diaphragm to appear higher, and vascular shadows to be obscured.¹⁰ The improved ability to detect these subtle differences should be weighed against the increased risk to HCWs required to perform PA and lateral CXR. A portable CXR exposes a relatively smaller number of staff who come to the bedside versus the larger number of people exposed in transporting the patient out of the room and into the hallway, elevator, and the radiology suite for a PA and lateral CXR.

• Avoid in-person evaluations in favor of virtual communication unless necessary.

To minimize HCW exposure to COVID-19 and optimize infection control, the CDC recommends the use of telemedicine when possible.⁷ Telemedicine refers to the use of technology to support clinical care across some distance, which includes video visits and remote clinical monitoring. At the time of writing, the Centers for Medicare & Medicaid Services had waived the rural site of care requirement for Medicare beneficiaries, granted 49 Medicaid waivers to states to enhance flexibility, and (at least temporarily) added inpatient care to the list of reimbursed telemedicine services.¹¹ Funding for expanded coverage under Medicare is included in the recent Coronavirus Preparedness and Response Supplemental Appropriations Act.¹² These federal changes open the door for commercial payers and state Medicaid programs to further boost telemedicine through reimbursement parity to in-person visits and other coverage policies. Hospitalists can ride this momentum and learn from ambulatory colleagues to harness the power of telemedicine and minimize unnecessary face-to-face interactions with patients who are suspected or confirmed to have COVID-19.¹³ Even if providers have to enter the patient’s room, telemedicine may still allow for large virtual family meetings despite strict visitor restrictions and physical distance with loved ones. If in-person visits are necessary, only one designated person should enter the patient’s room instead of the entire team.

• Do not delay goals of care conversations for hospitalized patients who are unlikely to benefit from life-sustaining treatments.

The COVID-19 pandemic amplifies the need for early goals of care discussions. Mortality rates range higher with acute respiratory distress syndrome from COVID-19, compared with other etiologies, and is associated with extended intensive care unit stays.¹⁴ The harms extend beyond the patient and families to our HCWs through psychological distress and heightened exposure from aerosolization during resuscitation. Advance care planning should center on the values and preferences of the patient. Rather than asking if the patient or family would want certain treatments, it is crucial for clinicians to be direct in making do-not-resuscitate recommendations if deemed futile care.¹⁵ This practice is well within legal confines and is distinct from withdrawal or withholding of life-sustaining resources.¹⁵

HCWs providing inpatient care during this pandemic remain among the highest risk for contracting the infection. As of April 9, 2020, nearly 9,300 HCWs in the United States have contracted COVID-19.¹⁶ One thing remains clear: If we want to protect our patients, we must start by protecting our HCWs. We must think critically to evaluate the potential harms to our extended healthcare teams and strive further to eliminate overuse from our care.

The authors represent members of the High Value Practice Academic Alliance. The High Value Practice Academic Alliance is a consortium of academic medical centers in the United States and Canada working to advance high-value healthcare through collaborative quality improvement, research, and education. Additional information is available at http://www.hvpaa.org.

With more than 3 million people diagnosed and more than 200,000 deaths worldwide at the time this article was written, coronavirus disease of 2019 (COVID-19) poses an unprecedented challenge to the public and to our healthcare system.¹ The United States has surpassed every other country in the total number of COVID-19 cases. Hospitals in hotspots are operating beyond capacity, while others prepare for a predicted surge of patients suffering from COVID-19. Now more than ever, clinicians need to prioritize limited time and resources wisely in this rapidly changing environment. Our most precious limited resource, healthcare workers (HCWs), bravely care for patients while trying to avoid acquiring the infection. With each test and treatment, clinicians must carefully consider harms and benefits, including exposing themselves and other HCWs to SARS-CoV-2, the virus causing this disease.

Delivering any healthcare service in which the potential harm exceeds benefit represents one form of overuse. In the era of COVID-19, the harmful consequences of overuse go beyond the patient to the healthcare team. For example, unnecessary chest computed tomography (CT) to help diagnose COVID-19 comes with the usual risks to the patient including radiation, but it may also reveal a suspicious nodule. That incidental finding can lead to downstream consequences, such as more imaging, blood work, and biopsy. In the current pandemic, however, that CT comes with more than just the usual risk. The initial unnecessary chest CT can risk exposing the transporter, the staff in the hallways and elevator en route, the radiology staff operating the CT scanner, and the maintenance staff who must clean the room and scanner afterward. Potential downstream harms to staff include exposure of the pulmonary and interventional radiology consultants, as well as the staff who perform repeat imaging after the biopsy. Evaluation of the nodule potentially prolongs the patient’s stay and exposes more staff. Clinicians must weigh the benefits and harms of each test and treatment carefully with consideration of both the patient and the staff involved. Moreover, it may turn out that the patient and staff without symptoms of COVID-19 may pose the most risk to one another.

Choosing Wisely® partnered with patients and clinician societies to develop a Top 5 recommendations list for eliminating unnecessary testing and treatment. Our multi-institutional group from the High Value Practice Academic Alliance proposed this Top 5 list of overuse practices in hospital medicine that can lead to harm of both patients and HCWs in the COVID-19 era (Table). The following recommendations apply to all patients with unsuspected, suspected, or confirmed SARS-CoV-2 infection in the hospital setting.

• Do not obtain nonurgent labs in separate blood draws if they can be batched together.

This recommendation expands on the original Society of Hospital Medicine Choosing Wisely recommendation: Don’t perform repetitive complete blood count and chemistry testing in the face of clinical and lab stability.² Aside from patient harms such as pain and hospital-acquired anemia, the risk of exposure to HCWs who perform phlebotomy (phlebotomists, nurses, and other clinicians), as well as staff who transport, handle, and process the bloodwork in the lab, must be minimized. Most prior interventions to eliminate unnecessary bloodwork focused on the number of lab tests,³ but some also aimed to batch nonurgent labs together to effectively reduce unnecessary needlesticks (“think twice, stick once”).⁴ This concept can be brought into this pandemic to provide safe and appropriate care for both patients and HCWs.

• Do not use bronchodilators unless there is active obstructive airway disease, and if needed, use metered dose inhalers instead of nebulizers.

We do not recommend using bronchodilators to treat COVID-19 symptoms unless patients develop acute bronchospastic symptoms of their underlying obstructive airway disease.⁵ When needed, use metered dose inhalers (MDIs),⁶ if available, instead of nebulizers because the latter potentiates aerosolization that could lead to higher risk of spreading the infection. The risk extends to respiratory technicians and nurses who administer the nebulizer, as well as other HCWs who enter the room during or after administration. The Centers for Disease Control and Prevention (CDC) considers nebulized bronchodilator therapy a “high-risk” exposure for HCWs not wearing the proper personal protectvie equipment.⁷ Moreover, MDI therapy produces equivalent outcomes to nebulized treatments for patients who are not critically ill.⁶ Unfortunately, the supply of MDIs during this crisis has not kept up with the increased demand.⁸

There are no clear guidelines for reuse of MDIs in COVID-19; however, options include labeling patients’ MDIs to use for hospitalization and discharge or labeling an MDI for use during hospitalization and then disinfecting for reuse. For safety reasons, MDIs of COVID-19 patients should be reused only for other patients with COVID-19.⁸

• Do not use posteroanterior and lateral chest X-ray as initial imaging. Use a portable chest X-ray instead.

The CDC does not currently recommend diagnosing COVID-19 by chest X-ray (CXR).⁷ When used appropriately, CXR can provide information to support a COVID-19 diagnosis and rule out other etiologies that cause respiratory symptoms.⁹ Posteroanterior (PA) and lateral CXR are more sensitive than portable CXR for detecting pleural effusions, and lateral CXR is needed to examine structures along the axis of the body. Portable CXR also may cause the heart to appear magnified and the mediastinum widened, the diaphragm to appear higher, and vascular shadows to be obscured.¹⁰ The improved ability to detect these subtle differences should be weighed against the increased risk to HCWs required to perform PA and lateral CXR. A portable CXR exposes a relatively smaller number of staff who come to the bedside versus the larger number of people exposed in transporting the patient out of the room and into the hallway, elevator, and the radiology suite for a PA and lateral CXR.

• Avoid in-person evaluations in favor of virtual communication unless necessary.

To minimize HCW exposure to COVID-19 and optimize infection control, the CDC recommends the use of telemedicine when possible.⁷ Telemedicine refers to the use of technology to support clinical care across some distance, which includes video visits and remote clinical monitoring. At the time of writing, the Centers for Medicare & Medicaid Services had waived the rural site of care requirement for Medicare beneficiaries, granted 49 Medicaid waivers to states to enhance flexibility, and (at least temporarily) added inpatient care to the list of reimbursed telemedicine services.¹¹ Funding for expanded coverage under Medicare is included in the recent Coronavirus Preparedness and Response Supplemental Appropriations Act.¹² These federal changes open the door for commercial payers and state Medicaid programs to further boost telemedicine through reimbursement parity to in-person visits and other coverage policies. Hospitalists can ride this momentum and learn from ambulatory colleagues to harness the power of telemedicine and minimize unnecessary face-to-face interactions with patients who are suspected or confirmed to have COVID-19.¹³ Even if providers have to enter the patient’s room, telemedicine may still allow for large virtual family meetings despite strict visitor restrictions and physical distance with loved ones. If in-person visits are necessary, only one designated person should enter the patient’s room instead of the entire team.

• Do not delay goals of care conversations for hospitalized patients who are unlikely to benefit from life-sustaining treatments.

The COVID-19 pandemic amplifies the need for early goals of care discussions. Mortality rates range higher with acute respiratory distress syndrome from COVID-19, compared with other etiologies, and is associated with extended intensive care unit stays.¹⁴ The harms extend beyond the patient and families to our HCWs through psychological distress and heightened exposure from aerosolization during resuscitation. Advance care planning should center on the values and preferences of the patient. Rather than asking if the patient or family would want certain treatments, it is crucial for clinicians to be direct in making do-not-resuscitate recommendations if deemed futile care.¹⁵ This practice is well within legal confines and is distinct from withdrawal or withholding of life-sustaining resources.¹⁵

HCWs providing inpatient care during this pandemic remain among the highest risk for contracting the infection. As of April 9, 2020, nearly 9,300 HCWs in the United States have contracted COVID-19.¹⁶ One thing remains clear: If we want to protect our patients, we must start by protecting our HCWs. We must think critically to evaluate the potential harms to our extended healthcare teams and strive further to eliminate overuse from our care.

The authors represent members of the High Value Practice Academic Alliance. The High Value Practice Academic Alliance is a consortium of academic medical centers in the United States and Canada working to advance high-value healthcare through collaborative quality improvement, research, and education. Additional information is available at http://www.hvpaa.org.

With the presence of hypertension in 25% of patients admitted to the hospital,¹ its proper management is imperative. A hypertensive crisis is a severe elevation of blood pressure, defined as systolic ≥180 mm Hg and/or diastolic ≥120 mm Hg. It is further classified as either a hypertensive emergency which includes the presence of end-organ damage,² or hypertensive urgency, defined as asymptomatic blood pressure elevation.³ Although hypertensive emergencies account for only 1%-2% of patients with hypertension,⁴ they are associated with a high one-year mortality rate (>79%).⁵ Hypertensive emergency requires immediate reduction of blood pressure with IV antihypertensive drugs to limit organ damage. In contrast, as per national guidelines, inpatient management of hypertensive urgency requires gradual reductions of blood pressure over hours to days using oral antihypertensives.² It is also recommended that alternative etiologies, such as anxiety or pain, be considered before treatment is initiated.¹

Clinicians often inappropriately treat asymptomatic hypertension in the inpatient setting,^6,7 using intravenous (IV) antihypertensive medications despite evidence showing potential harm.^5,8 This can lead to unpredictable reductions in blood pressure.^7,9 A recent retrospective analysis demonstrated that 32.6% of patients had a blood pressure reduction greater than 25% after the use of an IV antihypertensive.⁷ Reductions greater than 25% lead to shifts in autoregulation, which may result in patient harm, such as hypotension, decreased renal perfusion, and stroke.⁹ IV medications are also more expensive than oral agents, due to the additional cost of administration.

Although overtreatment of asymptomatic hypertension with IV antihypertensive medications is common,⁷ initiatives to address this in inpatient settings are lacking in the literature. The aim of this quality improvement initiative was to reduce unnecessary IV antihypertensive treatment for hypertensive urgency in the inpatient setting.

Setting

An interdisciplinary quality improvement intervention was initiated on two inpatient medicine units at an urban, 1,134-bed tertiary medical center affiliated with the Icahn School of Medicine at Mount Sinai. Members of the Mount Sinai High Value Care Committee and the Student High Value Care Initiative¹⁰ developed this project. The intervention was implemented in stages from March 2017 to February 2018. It targeted nurses, housestaff, nurse practitioners, and attendings on general medical teaching and nonteaching services. The components of the intervention included education, a treatment algorithm, audit and feedback, and electronic medical record (EMR) change. This project was submitted to the Quality Committee in the Department of Medicine and determined to be a quality improvement project rather than research and thus, an IRB submission was not required.

Treatment Algorithm and Education

A clinical algorithm was designed with nursing and cardiology representatives to provide guidance for nurses regarding the best practice for evaluation of inpatient hypertension, focusing on assessing patients before recommending treatment (“Assess Before Rx”; Figure 1). Educational sessions reinforcing the clinical algorithm were held monthly at nursing huddles. These involved an introduction session providing the background and purpose of the project, with follow-up sessions including interactive mock cases on the assessment of hypertensive urgency.

A second treatment algorithm was designed, with housestaff and cardiology input, to provide guidance for the internal medicine housestaff and nurse practitioners. It utilized a similar approach regarding identification, evaluation, and assessment of alternate etiologies but included more detailed treatment recommendations with a table outlining the oral medications used for hypertensive urgency (Figure 2). The flowchart and table were uploaded to an existing mobile application used by housestaff and nurse practitioners for quick access. The mobile application is frequently used by housestaff and contains many clinical resources. Additionally, e-mails including the purpose of the project and the treatment algorithm were sent to rotating housestaff at the start of each new medicine rotation.

Audit and Feedback

Monthly feedback was e-mailed to the nurses, which reinforced the goals and provided positive feedback on outcomes with an announcement of the “Nurse of the Month.” The winners were selected based on the most accurate and appropriate documentation of their assessments determined through retrospective chart review.

Targeted e-mail feedback was also sent to providers who ordered IV antihypertensives without the appropriate indication. The e-mails included the medical record number, date and time of the order, any alternate etiologies that were documented, and any adverse events that occurred as a result of the medication.

Systems Change: Electronic Medical Record Orders

EMR advisory warnings were placed on IV antihypertensive orders of labetalol and hydralazine. The alerts served to nonintrusively remind providers to assess for symptoms before placing the order to ensure that the order was appropriate.

Data Collection and Assessment

Seven-month preintervention (January-July 2016) and 12-month postintervention (March 2017-February 2018) data were compared. The months prior to intervention were excluded to account for project development and educational lag. Data were obtained from EMR utilization reports of one-time orders of IV labetalol and hydralazine, and retrospective chart review. Patients who were pregnant, less than 18 years of age, or postoperative were excluded. Orders were designated as inappropriate if there was no evidence of hypertensive emergency through documentation in progress notes, or if the patient was able to take oral medication (not NPO). Adverse events were defined as a blood pressure drop of more than 25%, a change in the heart rate by more than 20 beats per minute, or the need for IV fluids, based on previous studies.⁷ Although decreased blood pressure is not necessarily dangerous in and of itself, adverse events arising from blood pressure decreasing too rapidly from IV antihypertensives are well documented.^9,11 The presence of alternate etiologies of high blood pressure that were documented in progress notes, including pain, anxiety, agitation, and holding of home blood pressure medications, were recorded. The numbers of inappropriate orders pre- and postintervention were compared. Confounding factors of patient age and length of stay (LOS) were compared pre- and postintervention in order to rule out other factors to which the intervention’s effect could be attributed. Additionally, as a balancing measure, a random sample of patients with elevated blood pressure were monitored on a biweekly basis for adverse events that occurred as a result of not receiving IV treatment, including stroke, myocardial infarction, and pulmonary edema.

For this study, orders were reported on the standardized form of orders per 1,000 patient days. This was calculated as the number of orders divided by the total number of patient days from the two medicine units. For the univariate analysis, pre- and postintervention orders were compared for the different order categories using a t-test. Results were considered statistically significant at P < .05. Data analysis was conducted using SAS v. 9.4 (SAS Institute, Cary, North Carolina).

Additionally, a cost analysis was performed to estimate the hospital-wide annual cost of inappropriate orders. The analysis used the cost per dose¹² and included nurse-time derived from the median salary of those on our units. The hospital-wide cost was extrapolated to estimate the potential annual savings for the institution.

A total of 260 one-time orders of IV antihypertensives were analyzed in this study, 127 in the seven-month preintervention period and 133 in the 12-month postintervention period. The majority, 67.3% (n = 175), were labetalol orders. Inappropriate orders (ie, neither NPO nor hypertensive emergency) decreased from 8.3 to 3.3 orders per 1,000 patient days (P = .0099; Figure 3).

In total, there were 86 adverse events (33.1%), the majority of which (94.2%, n = 81) were a >25% decrease in blood pressure (Table 1). The number of adverse events per 1,000 patient days decreased from 4.4 in the preintervention period to 1.9 postintervention, P = .0112. Of the inappropriate orders, adverse events decreased from 3.7 to 0.8 per 1,000 patient days, P = .0072. Overall, there were 76 orders (29.2%) with documented alternate etiologies. The number of orders per 1,000 patient days with an alternate etiology decreased from 4.7 in the preintervention period to 1.2 postintervention, P =.0044 (Table 2). Descriptive analysis of patient characteristics pre- and postintervention were not statistically significant; for age 68.4 vs 70.7, P = .0823 and for LOS 14.8 vs 15.4, P = .0769. As a balancing measure, 111 patients with elevated blood pressure were monitored for adverse events during the postintervention period. Among patients who did not receive IV medication based on our algorithm, there were no adverse events.

Our initiative successfully demonstrated a significant reduction of 60% in inappropriate one-time orders of IV antihypertensives per 1,000 patient days. Accordingly, the number of adverse events per 1,000 patient days decreased by 57%. There was also a decrease in the number and percentage of IV orders with documented alternate etiologies. We hypothesize that this was due to nurses and physicians assessing and treating these conditions prior to treating hypertension in the intervention period, consequently avoiding an IV order.

The goal of the intervention was to have nurses assess for end-organ damage and alternate etiologies and include this information on their assessment provided to the physician, which would result in appropriate treatment of elevated blood pressure. By performing an interdisciplinary intervention, we addressed the knowledge deficit of both nurses and physicians, improved the triage of elevated blood pressure, and likely decreased the number of pages to providers.

To our knowledge, this is the first intervention addressing the inpatient overuse of IV antihypertensive medications for the treatment of asymptomatic hypertension. Additionally, this study bolsters prior evidence that the use of IV antihypertensives in asymptomatic patients leads to a large number of adverse events.⁷ A third of patients in the preintervention period had documented alternate etiologies of their blood pressure elevation, highlighting the need to assess and potentially treat these causes prior to treating blood pressure itself.

Reducing unnecessary treatment of asymptomatic blood pressure elevation is challenging. Evidence shows that both clinicians and patients overestimate the benefits and underestimate the harms of medical interventions.^13,14 This unfortunately leads to unjustified enthusiasm for medical treatments, which can worsen outcomes.¹⁵ Additionally, there may be a lack of knowledge of the guidelines, as well as the amount of time required in the full assessment of hypertensive urgency, that creates a culture of “treating the number.”

Changing physician behavior is difficult.¹⁶ However, active forms of continuing education and multifaceted interventions, such as ours, are most effective.¹⁷ Our message focused on patient safety and harm reduction, addressed clinicians’ safety concerns, and included stories of real cases where this overuse led to adverse events—all of which are encouraged in order to facilitate clinician engagement.¹⁸

There were limitations to this study. Only blood pressure elevations associated with an IV antihypertensive order and not all blood pressure elevations meeting the criteria for hypertensive urgency in general were examined. Additionally, our documentation of symptoms of hypertensive emergency and alternate etiologies was based only on documentation in the medical record. Ideally, we would have liked to conduct an interrupted time series analysis to assess the effect of the intervention over time; however, there were not enough orders of IV antihypertensives to perform such an analysis.

Treatment of asymptomatic blood pressure with IV antihypertensive medications can lead to patient harm. To reduce inappropriate treatment, our Student High Value Care team set out to challenge this common practice. Our interdisciplinary intervention successfully reduced unnecessary IV antihypertensive treatment. This may serve as a model for other institutions.

Disclosures

There are no relevant conflicts of interest to disclose for any authors.

With the presence of hypertension in 25% of patients admitted to the hospital,¹ its proper management is imperative. A hypertensive crisis is a severe elevation of blood pressure, defined as systolic ≥180 mm Hg and/or diastolic ≥120 mm Hg. It is further classified as either a hypertensive emergency which includes the presence of end-organ damage,² or hypertensive urgency, defined as asymptomatic blood pressure elevation.³ Although hypertensive emergencies account for only 1%-2% of patients with hypertension,⁴ they are associated with a high one-year mortality rate (>79%).⁵ Hypertensive emergency requires immediate reduction of blood pressure with IV antihypertensive drugs to limit organ damage. In contrast, as per national guidelines, inpatient management of hypertensive urgency requires gradual reductions of blood pressure over hours to days using oral antihypertensives.² It is also recommended that alternative etiologies, such as anxiety or pain, be considered before treatment is initiated.¹

Clinicians often inappropriately treat asymptomatic hypertension in the inpatient setting,^6,7 using intravenous (IV) antihypertensive medications despite evidence showing potential harm.^5,8 This can lead to unpredictable reductions in blood pressure.^7,9 A recent retrospective analysis demonstrated that 32.6% of patients had a blood pressure reduction greater than 25% after the use of an IV antihypertensive.⁷ Reductions greater than 25% lead to shifts in autoregulation, which may result in patient harm, such as hypotension, decreased renal perfusion, and stroke.⁹ IV medications are also more expensive than oral agents, due to the additional cost of administration.

Although overtreatment of asymptomatic hypertension with IV antihypertensive medications is common,⁷ initiatives to address this in inpatient settings are lacking in the literature. The aim of this quality improvement initiative was to reduce unnecessary IV antihypertensive treatment for hypertensive urgency in the inpatient setting.

Setting

An interdisciplinary quality improvement intervention was initiated on two inpatient medicine units at an urban, 1,134-bed tertiary medical center affiliated with the Icahn School of Medicine at Mount Sinai. Members of the Mount Sinai High Value Care Committee and the Student High Value Care Initiative¹⁰ developed this project. The intervention was implemented in stages from March 2017 to February 2018. It targeted nurses, housestaff, nurse practitioners, and attendings on general medical teaching and nonteaching services. The components of the intervention included education, a treatment algorithm, audit and feedback, and electronic medical record (EMR) change. This project was submitted to the Quality Committee in the Department of Medicine and determined to be a quality improvement project rather than research and thus, an IRB submission was not required.

Treatment Algorithm and Education

A clinical algorithm was designed with nursing and cardiology representatives to provide guidance for nurses regarding the best practice for evaluation of inpatient hypertension, focusing on assessing patients before recommending treatment (“Assess Before Rx”; Figure 1). Educational sessions reinforcing the clinical algorithm were held monthly at nursing huddles. These involved an introduction session providing the background and purpose of the project, with follow-up sessions including interactive mock cases on the assessment of hypertensive urgency.

A second treatment algorithm was designed, with housestaff and cardiology input, to provide guidance for the internal medicine housestaff and nurse practitioners. It utilized a similar approach regarding identification, evaluation, and assessment of alternate etiologies but included more detailed treatment recommendations with a table outlining the oral medications used for hypertensive urgency (Figure 2). The flowchart and table were uploaded to an existing mobile application used by housestaff and nurse practitioners for quick access. The mobile application is frequently used by housestaff and contains many clinical resources. Additionally, e-mails including the purpose of the project and the treatment algorithm were sent to rotating housestaff at the start of each new medicine rotation.

Audit and Feedback

Monthly feedback was e-mailed to the nurses, which reinforced the goals and provided positive feedback on outcomes with an announcement of the “Nurse of the Month.” The winners were selected based on the most accurate and appropriate documentation of their assessments determined through retrospective chart review.

Targeted e-mail feedback was also sent to providers who ordered IV antihypertensives without the appropriate indication. The e-mails included the medical record number, date and time of the order, any alternate etiologies that were documented, and any adverse events that occurred as a result of the medication.

Systems Change: Electronic Medical Record Orders

EMR advisory warnings were placed on IV antihypertensive orders of labetalol and hydralazine. The alerts served to nonintrusively remind providers to assess for symptoms before placing the order to ensure that the order was appropriate.

Data Collection and Assessment

Seven-month preintervention (January-July 2016) and 12-month postintervention (March 2017-February 2018) data were compared. The months prior to intervention were excluded to account for project development and educational lag. Data were obtained from EMR utilization reports of one-time orders of IV labetalol and hydralazine, and retrospective chart review. Patients who were pregnant, less than 18 years of age, or postoperative were excluded. Orders were designated as inappropriate if there was no evidence of hypertensive emergency through documentation in progress notes, or if the patient was able to take oral medication (not NPO). Adverse events were defined as a blood pressure drop of more than 25%, a change in the heart rate by more than 20 beats per minute, or the need for IV fluids, based on previous studies.⁷ Although decreased blood pressure is not necessarily dangerous in and of itself, adverse events arising from blood pressure decreasing too rapidly from IV antihypertensives are well documented.^9,11 The presence of alternate etiologies of high blood pressure that were documented in progress notes, including pain, anxiety, agitation, and holding of home blood pressure medications, were recorded. The numbers of inappropriate orders pre- and postintervention were compared. Confounding factors of patient age and length of stay (LOS) were compared pre- and postintervention in order to rule out other factors to which the intervention’s effect could be attributed. Additionally, as a balancing measure, a random sample of patients with elevated blood pressure were monitored on a biweekly basis for adverse events that occurred as a result of not receiving IV treatment, including stroke, myocardial infarction, and pulmonary edema.

For this study, orders were reported on the standardized form of orders per 1,000 patient days. This was calculated as the number of orders divided by the total number of patient days from the two medicine units. For the univariate analysis, pre- and postintervention orders were compared for the different order categories using a t-test. Results were considered statistically significant at P < .05. Data analysis was conducted using SAS v. 9.4 (SAS Institute, Cary, North Carolina).

Additionally, a cost analysis was performed to estimate the hospital-wide annual cost of inappropriate orders. The analysis used the cost per dose¹² and included nurse-time derived from the median salary of those on our units. The hospital-wide cost was extrapolated to estimate the potential annual savings for the institution.

A total of 260 one-time orders of IV antihypertensives were analyzed in this study, 127 in the seven-month preintervention period and 133 in the 12-month postintervention period. The majority, 67.3% (n = 175), were labetalol orders. Inappropriate orders (ie, neither NPO nor hypertensive emergency) decreased from 8.3 to 3.3 orders per 1,000 patient days (P = .0099; Figure 3).

In total, there were 86 adverse events (33.1%), the majority of which (94.2%, n = 81) were a >25% decrease in blood pressure (Table 1). The number of adverse events per 1,000 patient days decreased from 4.4 in the preintervention period to 1.9 postintervention, P = .0112. Of the inappropriate orders, adverse events decreased from 3.7 to 0.8 per 1,000 patient days, P = .0072. Overall, there were 76 orders (29.2%) with documented alternate etiologies. The number of orders per 1,000 patient days with an alternate etiology decreased from 4.7 in the preintervention period to 1.2 postintervention, P =.0044 (Table 2). Descriptive analysis of patient characteristics pre- and postintervention were not statistically significant; for age 68.4 vs 70.7, P = .0823 and for LOS 14.8 vs 15.4, P = .0769. As a balancing measure, 111 patients with elevated blood pressure were monitored for adverse events during the postintervention period. Among patients who did not receive IV medication based on our algorithm, there were no adverse events.

Our initiative successfully demonstrated a significant reduction of 60% in inappropriate one-time orders of IV antihypertensives per 1,000 patient days. Accordingly, the number of adverse events per 1,000 patient days decreased by 57%. There was also a decrease in the number and percentage of IV orders with documented alternate etiologies. We hypothesize that this was due to nurses and physicians assessing and treating these conditions prior to treating hypertension in the intervention period, consequently avoiding an IV order.

The goal of the intervention was to have nurses assess for end-organ damage and alternate etiologies and include this information on their assessment provided to the physician, which would result in appropriate treatment of elevated blood pressure. By performing an interdisciplinary intervention, we addressed the knowledge deficit of both nurses and physicians, improved the triage of elevated blood pressure, and likely decreased the number of pages to providers.

To our knowledge, this is the first intervention addressing the inpatient overuse of IV antihypertensive medications for the treatment of asymptomatic hypertension. Additionally, this study bolsters prior evidence that the use of IV antihypertensives in asymptomatic patients leads to a large number of adverse events.⁷ A third of patients in the preintervention period had documented alternate etiologies of their blood pressure elevation, highlighting the need to assess and potentially treat these causes prior to treating blood pressure itself.

Reducing unnecessary treatment of asymptomatic blood pressure elevation is challenging. Evidence shows that both clinicians and patients overestimate the benefits and underestimate the harms of medical interventions.^13,14 This unfortunately leads to unjustified enthusiasm for medical treatments, which can worsen outcomes.¹⁵ Additionally, there may be a lack of knowledge of the guidelines, as well as the amount of time required in the full assessment of hypertensive urgency, that creates a culture of “treating the number.”

Changing physician behavior is difficult.¹⁶ However, active forms of continuing education and multifaceted interventions, such as ours, are most effective.¹⁷ Our message focused on patient safety and harm reduction, addressed clinicians’ safety concerns, and included stories of real cases where this overuse led to adverse events—all of which are encouraged in order to facilitate clinician engagement.¹⁸

There were limitations to this study. Only blood pressure elevations associated with an IV antihypertensive order and not all blood pressure elevations meeting the criteria for hypertensive urgency in general were examined. Additionally, our documentation of symptoms of hypertensive emergency and alternate etiologies was based only on documentation in the medical record. Ideally, we would have liked to conduct an interrupted time series analysis to assess the effect of the intervention over time; however, there were not enough orders of IV antihypertensives to perform such an analysis.

Treatment of asymptomatic blood pressure with IV antihypertensive medications can lead to patient harm. To reduce inappropriate treatment, our Student High Value Care team set out to challenge this common practice. Our interdisciplinary intervention successfully reduced unnecessary IV antihypertensive treatment. This may serve as a model for other institutions.

Disclosures

There are no relevant conflicts of interest to disclose for any authors.

With the presence of hypertension in 25% of patients admitted to the hospital,¹ its proper management is imperative. A hypertensive crisis is a severe elevation of blood pressure, defined as systolic ≥180 mm Hg and/or diastolic ≥120 mm Hg. It is further classified as either a hypertensive emergency which includes the presence of end-organ damage,² or hypertensive urgency, defined as asymptomatic blood pressure elevation.³ Although hypertensive emergencies account for only 1%-2% of patients with hypertension,⁴ they are associated with a high one-year mortality rate (>79%).⁵ Hypertensive emergency requires immediate reduction of blood pressure with IV antihypertensive drugs to limit organ damage. In contrast, as per national guidelines, inpatient management of hypertensive urgency requires gradual reductions of blood pressure over hours to days using oral antihypertensives.² It is also recommended that alternative etiologies, such as anxiety or pain, be considered before treatment is initiated.¹

Clinicians often inappropriately treat asymptomatic hypertension in the inpatient setting,^6,7 using intravenous (IV) antihypertensive medications despite evidence showing potential harm.^5,8 This can lead to unpredictable reductions in blood pressure.^7,9 A recent retrospective analysis demonstrated that 32.6% of patients had a blood pressure reduction greater than 25% after the use of an IV antihypertensive.⁷ Reductions greater than 25% lead to shifts in autoregulation, which may result in patient harm, such as hypotension, decreased renal perfusion, and stroke.⁹ IV medications are also more expensive than oral agents, due to the additional cost of administration.

Although overtreatment of asymptomatic hypertension with IV antihypertensive medications is common,⁷ initiatives to address this in inpatient settings are lacking in the literature. The aim of this quality improvement initiative was to reduce unnecessary IV antihypertensive treatment for hypertensive urgency in the inpatient setting.

Setting

An interdisciplinary quality improvement intervention was initiated on two inpatient medicine units at an urban, 1,134-bed tertiary medical center affiliated with the Icahn School of Medicine at Mount Sinai. Members of the Mount Sinai High Value Care Committee and the Student High Value Care Initiative¹⁰ developed this project. The intervention was implemented in stages from March 2017 to February 2018. It targeted nurses, housestaff, nurse practitioners, and attendings on general medical teaching and nonteaching services. The components of the intervention included education, a treatment algorithm, audit and feedback, and electronic medical record (EMR) change. This project was submitted to the Quality Committee in the Department of Medicine and determined to be a quality improvement project rather than research and thus, an IRB submission was not required.

Treatment Algorithm and Education

A clinical algorithm was designed with nursing and cardiology representatives to provide guidance for nurses regarding the best practice for evaluation of inpatient hypertension, focusing on assessing patients before recommending treatment (“Assess Before Rx”; Figure 1). Educational sessions reinforcing the clinical algorithm were held monthly at nursing huddles. These involved an introduction session providing the background and purpose of the project, with follow-up sessions including interactive mock cases on the assessment of hypertensive urgency.

A second treatment algorithm was designed, with housestaff and cardiology input, to provide guidance for the internal medicine housestaff and nurse practitioners. It utilized a similar approach regarding identification, evaluation, and assessment of alternate etiologies but included more detailed treatment recommendations with a table outlining the oral medications used for hypertensive urgency (Figure 2). The flowchart and table were uploaded to an existing mobile application used by housestaff and nurse practitioners for quick access. The mobile application is frequently used by housestaff and contains many clinical resources. Additionally, e-mails including the purpose of the project and the treatment algorithm were sent to rotating housestaff at the start of each new medicine rotation.

Audit and Feedback

Monthly feedback was e-mailed to the nurses, which reinforced the goals and provided positive feedback on outcomes with an announcement of the “Nurse of the Month.” The winners were selected based on the most accurate and appropriate documentation of their assessments determined through retrospective chart review.

Targeted e-mail feedback was also sent to providers who ordered IV antihypertensives without the appropriate indication. The e-mails included the medical record number, date and time of the order, any alternate etiologies that were documented, and any adverse events that occurred as a result of the medication.

Systems Change: Electronic Medical Record Orders

EMR advisory warnings were placed on IV antihypertensive orders of labetalol and hydralazine. The alerts served to nonintrusively remind providers to assess for symptoms before placing the order to ensure that the order was appropriate.

Data Collection and Assessment

Seven-month preintervention (January-July 2016) and 12-month postintervention (March 2017-February 2018) data were compared. The months prior to intervention were excluded to account for project development and educational lag. Data were obtained from EMR utilization reports of one-time orders of IV labetalol and hydralazine, and retrospective chart review. Patients who were pregnant, less than 18 years of age, or postoperative were excluded. Orders were designated as inappropriate if there was no evidence of hypertensive emergency through documentation in progress notes, or if the patient was able to take oral medication (not NPO). Adverse events were defined as a blood pressure drop of more than 25%, a change in the heart rate by more than 20 beats per minute, or the need for IV fluids, based on previous studies.⁷ Although decreased blood pressure is not necessarily dangerous in and of itself, adverse events arising from blood pressure decreasing too rapidly from IV antihypertensives are well documented.^9,11 The presence of alternate etiologies of high blood pressure that were documented in progress notes, including pain, anxiety, agitation, and holding of home blood pressure medications, were recorded. The numbers of inappropriate orders pre- and postintervention were compared. Confounding factors of patient age and length of stay (LOS) were compared pre- and postintervention in order to rule out other factors to which the intervention’s effect could be attributed. Additionally, as a balancing measure, a random sample of patients with elevated blood pressure were monitored on a biweekly basis for adverse events that occurred as a result of not receiving IV treatment, including stroke, myocardial infarction, and pulmonary edema.

For this study, orders were reported on the standardized form of orders per 1,000 patient days. This was calculated as the number of orders divided by the total number of patient days from the two medicine units. For the univariate analysis, pre- and postintervention orders were compared for the different order categories using a t-test. Results were considered statistically significant at P < .05. Data analysis was conducted using SAS v. 9.4 (SAS Institute, Cary, North Carolina).

Additionally, a cost analysis was performed to estimate the hospital-wide annual cost of inappropriate orders. The analysis used the cost per dose¹² and included nurse-time derived from the median salary of those on our units. The hospital-wide cost was extrapolated to estimate the potential annual savings for the institution.

A total of 260 one-time orders of IV antihypertensives were analyzed in this study, 127 in the seven-month preintervention period and 133 in the 12-month postintervention period. The majority, 67.3% (n = 175), were labetalol orders. Inappropriate orders (ie, neither NPO nor hypertensive emergency) decreased from 8.3 to 3.3 orders per 1,000 patient days (P = .0099; Figure 3).

In total, there were 86 adverse events (33.1%), the majority of which (94.2%, n = 81) were a >25% decrease in blood pressure (Table 1). The number of adverse events per 1,000 patient days decreased from 4.4 in the preintervention period to 1.9 postintervention, P = .0112. Of the inappropriate orders, adverse events decreased from 3.7 to 0.8 per 1,000 patient days, P = .0072. Overall, there were 76 orders (29.2%) with documented alternate etiologies. The number of orders per 1,000 patient days with an alternate etiology decreased from 4.7 in the preintervention period to 1.2 postintervention, P =.0044 (Table 2). Descriptive analysis of patient characteristics pre- and postintervention were not statistically significant; for age 68.4 vs 70.7, P = .0823 and for LOS 14.8 vs 15.4, P = .0769. As a balancing measure, 111 patients with elevated blood pressure were monitored for adverse events during the postintervention period. Among patients who did not receive IV medication based on our algorithm, there were no adverse events.

Our initiative successfully demonstrated a significant reduction of 60% in inappropriate one-time orders of IV antihypertensives per 1,000 patient days. Accordingly, the number of adverse events per 1,000 patient days decreased by 57%. There was also a decrease in the number and percentage of IV orders with documented alternate etiologies. We hypothesize that this was due to nurses and physicians assessing and treating these conditions prior to treating hypertension in the intervention period, consequently avoiding an IV order.

The goal of the intervention was to have nurses assess for end-organ damage and alternate etiologies and include this information on their assessment provided to the physician, which would result in appropriate treatment of elevated blood pressure. By performing an interdisciplinary intervention, we addressed the knowledge deficit of both nurses and physicians, improved the triage of elevated blood pressure, and likely decreased the number of pages to providers.

To our knowledge, this is the first intervention addressing the inpatient overuse of IV antihypertensive medications for the treatment of asymptomatic hypertension. Additionally, this study bolsters prior evidence that the use of IV antihypertensives in asymptomatic patients leads to a large number of adverse events.⁷ A third of patients in the preintervention period had documented alternate etiologies of their blood pressure elevation, highlighting the need to assess and potentially treat these causes prior to treating blood pressure itself.

Reducing unnecessary treatment of asymptomatic blood pressure elevation is challenging. Evidence shows that both clinicians and patients overestimate the benefits and underestimate the harms of medical interventions.^13,14 This unfortunately leads to unjustified enthusiasm for medical treatments, which can worsen outcomes.¹⁵ Additionally, there may be a lack of knowledge of the guidelines, as well as the amount of time required in the full assessment of hypertensive urgency, that creates a culture of “treating the number.”

Changing physician behavior is difficult.¹⁶ However, active forms of continuing education and multifaceted interventions, such as ours, are most effective.¹⁷ Our message focused on patient safety and harm reduction, addressed clinicians’ safety concerns, and included stories of real cases where this overuse led to adverse events—all of which are encouraged in order to facilitate clinician engagement.¹⁸

There were limitations to this study. Only blood pressure elevations associated with an IV antihypertensive order and not all blood pressure elevations meeting the criteria for hypertensive urgency in general were examined. Additionally, our documentation of symptoms of hypertensive emergency and alternate etiologies was based only on documentation in the medical record. Ideally, we would have liked to conduct an interrupted time series analysis to assess the effect of the intervention over time; however, there were not enough orders of IV antihypertensives to perform such an analysis.

Treatment of asymptomatic blood pressure with IV antihypertensive medications can lead to patient harm. To reduce inappropriate treatment, our Student High Value Care team set out to challenge this common practice. Our interdisciplinary intervention successfully reduced unnecessary IV antihypertensive treatment. This may serve as a model for other institutions.

Disclosures

There are no relevant conflicts of interest to disclose for any authors.

The case

A 50-year old woman naive to the health care system presents to the ED with nausea, malaise, and decreased exercise tolerance for several weeks. Physical exam reveals mild bilateral lower extremity edema. Her labs are notable for an elevated creatinine of 7.0. She is admitted for work-up of her renal disease.

Nephrology was consulted and recommended obtaining urine electrolytes. The admitting hospitalist is unsure which urine electrolytes are appropriate to order, and in turn orders all of the urine electrolytes in the order set.

Which urine electrolytes should be ordered in various clinical contexts?
 

Introduction

Hospitalists have been on the forefront of efforts to tailor testing and resource utilization to eliminate wasteful practices in health care. To order and interpret diagnostic tests appropriately, a hospitalist needs to have a thorough understanding of the diagnostic utility of laboratory tests. There is a lack of clear diagnostic guidelines, so ordering all the urine electrolytes in a “blanket” strategy is a common practice. We will discuss the diagnostic utility of each of the urine electrolytes in a variety of clinical scenarios.

Acute kidney injury

Both the fractional excretion of sodium (FENa) and the fractional excretion of urea (FEUrea) have long been used as part of the standard work-up for determining if acute kidney injury (AKI) is due to prerenal causes. Although these markers prove to be beneficial in the work-up of AKI, both the FENa and FEUrea have several limitations.

FENa measures the ratio of sodium excreted in the urine compared to how much is filtered through the kidney. A FENa of less than 1% in oliguric patients may indicate prerenal azotemia, as an increased reabsorption of sodium is the appropriate response of functioning nephrons to decreased renal perfusion. Values greater than 3% may be consistent with acute tubular necrosis (ATN) due to inappropriate sodium excretion in the setting of tubular damage.

Importantly, a FENa value of less than 1% occurs in a number of conditions other than prerenal azotemia due to dehydration, including hypervolemic prerenal states such as cirrhosis or heart failure; AKI due to radiocontrast or heme pigments; acute glomerulonephritis; transition from prerenal to postischemic ATN or sepsis, and in acute interstitial nephritis (AIN).^1,2 Approximately 10% of patients with nonoliguric ATN have a FENa less than 1.0%. Moreover, use of diuretics can falsely elevate the FENa due to inhibition of sodium reabsorption. FENa values above 3% can occur in volume contraction in patients with chronic kidney disease (CKD) or in elderly patients as their sodium reabsorption is impaired.³ Acute volume loss (e.g. blood loss), or more commonly, administration of diuretics or intravenous fluids, can also alter the interpretation of the FENa.²

Hyponatremia

Hyponatremia is the most common electrolyte abnormality in hospitalized patients, with a prevalence of up to 30% in critically ill patients.⁴ It often is acquired during the hospitalization itself. A detailed history and physical exam, including careful assessment of volume status, is as important as laboratory values in establishing the cause of hyponatremia.

Urine sodium and urine osmolality are measured to understand whether the renin-aldosterone-angiotensin system (RAAS) and antidiuretic hormone (ADH) are activated. If renal blood flow or renal delivery of sodium is decreased, renin secretion from the juxtaglomerular apparatus will be activated, ultimately leading to increased reabsorption of sodium in the distal tubules and collecting ducts. Thus, low urine sodium signals that the RAAS is activated due to decreased serum sodium concentration or decreased renal blood flow from hypovolemia or low effective arterial circulation from cirrhosis or heart failure.

Most causes of hyponatremia will have low urine sodium values, including hypovolemia, cirrhosis, heart failure, “tea-and-toast” diet, beer potomania, and primary polydipsia. However, the urine sodium may be unreliable in patients who are not oliguric or who have CKD.

Diuretic-induced hyponatremia from thiazide or loop diuretics will likely have elevated urine sodium levels. Similarly, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) will have an elevated urine sodium above 20-40 mEq/L.

Urine osmolality becomes elevated when ADH is secreted in response to reduced plasma volume or increased plasma osmolality. Urine osmolality is low in cases such as primary polydipsia, which creates a maximally dilute urine of 40-100 mEq/L, and in tea-and-toast diets or beer potomania due to low solute intake. Urine osmolality can be elevated in hypovolemic states as well as SIADH, and is variable in hypothyroidism and selective serotonin reuptake inhibitor administration. Thus, urine sodium, and not urine osmolality, is the most useful differentiator between SIADH and hypovolemic states.

In a study of 555 patients with hyponatremia secondary to SIADH, mean urine sodium was found to be 72 (range 30-251) and the median urine osmolality was 379 (range 123-1019).⁵

In cases of marked hyperglycemia, serum osmolality should be measured to evaluate hyperglycemia as a cause of hyperosmolar hyponatremia. Pseudohyponatremia in the setting of hyperlipidemia, hypertriglyceridemia, or hyperparaproteinemia represents a laboratory artifact due to lower plasma water concentration in the specimen sample and should be excluded.
 

Hypokalemia

About 20% of patients are hypokalemic during an inpatient hospitalization. There is a broad differential for hypokalemia, including medical, nutritional, and medication-related causes. Exogenous insulin administration or endogenous production in cases of refeeding syndrome drives potassium intracellularly via the N+/K+ ATPase. Increased sympathetic activity from alcohol withdrawal, acute myocardial infarction, head injury, or thyroid imbalance, as well as iatrogenic causes such as albuterol administration, also drive potassium intracellularly. Diarrhea and nasogastric tube suction lead to gastrointestinal (GI) potassium losses, while antibiotics, chemotherapeutic agents, and diuretics can cause hypokalemia through renal potassium wasting. Hyperaldosteronism and renal tubular acidosis are less common causes.⁶

The history, review of medications, physical exam, and initial basic laboratory testing (electrolytes, BUN, creatinine, magnesium) should assess for pseudohypokalemia, poor oral intake, diuretic use, acid-base disturbances, or GI losses.

Measuring urine potassium is useful in the work-up of the hypokalemic patient when these conditions are not evident. Urine potassium – either 24-hour or spot urine potassium-to-creatinine ratio – can help determine if urinary potassium wasting is a factor. Potassium is excreted at a near constant rate throughout the day. A urine potassium-to-creatinine ratio corrects for variations in urine volume. When this ratio is greater than 13 mEq/g, renal potassium losses should be suspected. If the ratio is less than 13 mEq/g, hypokalemia is likely due to transcellular potassium shifts, GI losses, diuretics, or poor intake.

Hyperkalemia

Several concepts in hypokalemia are relevant to hyperkalemia. Redistribution of potassium into the extracellular fluid can cause hyperkalemia when the body tries to counterbalance low extracellular pH by potassium-hydrogen exchange. Medications may cause an extracellular shift of potassium (e.g. digoxin) or induce diminished potassium excretion (e.g. NSAIDs, spironolactone, ACE/ARBs).

CKD and end-stage kidney disease are common causes of hyperkalemia in the hospitalized patient – as functioning nephrons decrease, poor Na-K exchange ensues. Hypoaldosteronism and type 4 renal tubular acidosis are also on the differential diagnosis. Pseudohyperkalemia secondary to thrombocytosis, erythrocytosis, or activated platelets should be considered and evaluated.

Appropriate renal excretion of potassium is mediated by the connecting segment between the distal tubule and the collecting duct, and the cortical collecting duct itself. There are four major causes of hyperkalemia due to reduced urinary potassium secretion: reduced aldosterone secretion, reduced response to aldosterone, reduced distal sodium and water delivery (often related to low effective arterial blood volume), and kidney injury.⁶

Measurement of 24-hour urinary potassium excretion is of limited utility in patients with persistent stable hyperkalemia because urinary potassium excretion is related to potassium intake. The TTKG was previously used to assess the degree of aldosterone activity by estimating the potassium concentration in the cortical collecting tubule. However, some assumptions upon which this calculation was based have been considered invalid by the original studies’ authors, and the TTKG to evaluate potassium abnormalities is no longer uniformly recommended.^7,8 Ultimately, if patients have persistent hyperkalemia, work-up for hypoaldosteronism should be considered.
 

Normal anion gap metabolic acidosis

The urine anion gap (UAG) is used to determine the cause of normal anion gap hyperchloremic metabolic acidosis by indirectly measuring urinary excretion of ammonium. To maintain a normal acid/base balance, hydrogen ions are excreted in the urine with simultaneous reabsorption of bicarbonate. Hydrogen ions are bound to ammonia (NH3) to form ammonium (NH4+), which is excreted as NH4Cl in the urine.

The UAG is calculated by adding urine sodium and urine potassium and subtracting urine chloride (see Table 1). In a patient without an acid/base disturbance, the UAG is positive because more Na and K is absorbed in the gastrointestinal system compared to Cl, and thus more Na and K is excreted in the urine. In a normal anion gap metabolic acidosis through an acid load or bicarbonate loss, the normal response of the kidney is to excrete more hydrogen ions, resulting in more chloride excretion as NH4Cl. This leads to a negative urine anion gap, as Cl excretion outweighs Na and K excretion. When NH4+ excretion is impaired, such as in distal renal tubular acidosis (RTA), the urine anion gap will remain positive despite the metabolic acidosis. Thus, a positive UAG points to renal causes of the normal anion gap metabolic acidosis, whereas a negative UAG points to extrarenal causes such as bicarbonate losses in the GI tract.⁹
 

Additional considerations

Urine studies can also be useful for assessment of proteinuria and albuminuria in a patient with CKD or diabetes, diagnosis of plasma cell dyscrasias, the diagnosis and prevention of nephrolithiasis, and a wide variety of other conditions.

Back to the case

Our patient was admitted with an elevated creatinine of unclear chronicity, and subacute symptoms of uremia. Because she was oliguric, urine and serum sodium and creatinine were measured before intravenous fluids were administered. Her FENa was 2%, which was not consistent with prerenal azotemia or ATN. She was found to have CKD secondary to previously undiagnosed diabetes. Upon further questioning, she had been taking high-dose NSAIDs for her chronic knee pain. Her renal function improved mildly by withholding NSAIDs, and she was discharged with appropriate nephrology follow-up.

Bottom line

Urine electrolytes have specific indications and utilities for different clinical scenarios, and should be ordered in a targeted manner that can aide in diagnosing AKI, hyponatremia, hypokalemia, and normal anion gap metabolic acidosis.

Dr. Tummalapalli, Dr. Krouss, and Dr. Goetz are hospitalists in the department of medicine at the Icahn School of Medicine at Mount Sinai in New York City.

References

1. Brosius FC, Lau K. Low fractional excretion of sodium in acute renal failure: role of timing of the test and ischemia. Am J Nephrol. 1986;6(6):450-7.

2. Gottfried J, Weisen J, Raina R, Nally J. Finding the cause of acute kidney injury: Which index of fractional excretion is better? Cleve Clin J Med. 2012;79(2):121-6.

3. Steiner, RW. Interpreting the fractional excretion of sodium. Am J Med. 1984;77(4):699-702.

4. DeVita MV, Gardenswartz MH, Konecky A, Zabetakis PM. Incidence and etiology of hyponatremia in an intensive care unit. Clin Nephrol. 1990;34(4):163-6.

5. Shepshelovich D, Leibovitch C, Klein A, et al. The syndrome of inappropriate antidiuretic hormone secretion: distribution and characterization according to etiologies. Eur J Int Med. 2015;26(10):819-24.

6. Mount DB. Fluid and Electrolyte Disturbances. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill; 2015.

7. Kamel KS. Intrarenal urea recycling leads to a higher rate of renal excretion of potassium: an hypothesis with clinical implications. Curr Opin Nephrol Hypertens. 2011 Sep;20(5):547-54.

8. Kamel KS, Davids MR, Lin S-H, Halperin ML. Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine. In: Brenner and Rector’s The Kidney, 27, 804-45.e2. Philadelphia, PA: Elsevier; 2016.

9. Goldstein MB, Bear R, Richardson RMA, Marsden PA, Halperin ML. The Urine Anion Gap: a clinically useful index of ammonium excretion. Am J Med Sci. 1986;198-202.

Key Points:

• In acute kidney injury, the FENa and FEUrea may be calculated to distinguish prerenal azotemia from ATN; however, FENa and FEUrea may be low in a wide variety of conditions other than prerenal azotemia.

• Urine sodium and osmolality values are helpful in diagnosing the cause of hyponatremia, but have a number of limitations in nonoliguric patients and those with CKD.

• An elevated transtubular potassium gradient (TTKG) may indicate renal loss of potassium in patients with hypokalemia.

• A positive urine anion gap (UAG) in the setting of a normal anion gap metabolic acidosis points to renal causes of the metabolic acidosis, whereas a negative UAG points to extrarenal causes such as bicarbonate losses in the GI tract.Ad

Additional Reading:

Goldstein MB, Bear R, Richardson RMA, Marsden PA, Halperin ML. The Urine Anion Gap: A Clinically Useful Index of Ammonium Excretion. Am J Med Sci. 1986;198-202.

Gotfried J, Wiesen J, Raina R, Nally Jr JV. Finding the cause of acute kidney injury: which index of fractional excretion is better. Cleve Clin J Med. 2012;79(2):121-126.

Kamel KS, Davids MR, Lin S-H, Halperin ML. Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine. In: Brenner and Rector’s The Kidney, 27, 804-845.e2. Philadelphia, PA: Elsevier; 2016.

The case

A 50-year old woman naive to the health care system presents to the ED with nausea, malaise, and decreased exercise tolerance for several weeks. Physical exam reveals mild bilateral lower extremity edema. Her labs are notable for an elevated creatinine of 7.0. She is admitted for work-up of her renal disease.

Nephrology was consulted and recommended obtaining urine electrolytes. The admitting hospitalist is unsure which urine electrolytes are appropriate to order, and in turn orders all of the urine electrolytes in the order set.

Which urine electrolytes should be ordered in various clinical contexts?
 

Introduction

Hospitalists have been on the forefront of efforts to tailor testing and resource utilization to eliminate wasteful practices in health care. To order and interpret diagnostic tests appropriately, a hospitalist needs to have a thorough understanding of the diagnostic utility of laboratory tests. There is a lack of clear diagnostic guidelines, so ordering all the urine electrolytes in a “blanket” strategy is a common practice. We will discuss the diagnostic utility of each of the urine electrolytes in a variety of clinical scenarios.

Acute kidney injury

Both the fractional excretion of sodium (FENa) and the fractional excretion of urea (FEUrea) have long been used as part of the standard work-up for determining if acute kidney injury (AKI) is due to prerenal causes. Although these markers prove to be beneficial in the work-up of AKI, both the FENa and FEUrea have several limitations.

FENa measures the ratio of sodium excreted in the urine compared to how much is filtered through the kidney. A FENa of less than 1% in oliguric patients may indicate prerenal azotemia, as an increased reabsorption of sodium is the appropriate response of functioning nephrons to decreased renal perfusion. Values greater than 3% may be consistent with acute tubular necrosis (ATN) due to inappropriate sodium excretion in the setting of tubular damage.

Importantly, a FENa value of less than 1% occurs in a number of conditions other than prerenal azotemia due to dehydration, including hypervolemic prerenal states such as cirrhosis or heart failure; AKI due to radiocontrast or heme pigments; acute glomerulonephritis; transition from prerenal to postischemic ATN or sepsis, and in acute interstitial nephritis (AIN).^1,2 Approximately 10% of patients with nonoliguric ATN have a FENa less than 1.0%. Moreover, use of diuretics can falsely elevate the FENa due to inhibition of sodium reabsorption. FENa values above 3% can occur in volume contraction in patients with chronic kidney disease (CKD) or in elderly patients as their sodium reabsorption is impaired.³ Acute volume loss (e.g. blood loss), or more commonly, administration of diuretics or intravenous fluids, can also alter the interpretation of the FENa.²

Hyponatremia

Hyponatremia is the most common electrolyte abnormality in hospitalized patients, with a prevalence of up to 30% in critically ill patients.⁴ It often is acquired during the hospitalization itself. A detailed history and physical exam, including careful assessment of volume status, is as important as laboratory values in establishing the cause of hyponatremia.

Urine sodium and urine osmolality are measured to understand whether the renin-aldosterone-angiotensin system (RAAS) and antidiuretic hormone (ADH) are activated. If renal blood flow or renal delivery of sodium is decreased, renin secretion from the juxtaglomerular apparatus will be activated, ultimately leading to increased reabsorption of sodium in the distal tubules and collecting ducts. Thus, low urine sodium signals that the RAAS is activated due to decreased serum sodium concentration or decreased renal blood flow from hypovolemia or low effective arterial circulation from cirrhosis or heart failure.

Most causes of hyponatremia will have low urine sodium values, including hypovolemia, cirrhosis, heart failure, “tea-and-toast” diet, beer potomania, and primary polydipsia. However, the urine sodium may be unreliable in patients who are not oliguric or who have CKD.

Diuretic-induced hyponatremia from thiazide or loop diuretics will likely have elevated urine sodium levels. Similarly, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) will have an elevated urine sodium above 20-40 mEq/L.

Urine osmolality becomes elevated when ADH is secreted in response to reduced plasma volume or increased plasma osmolality. Urine osmolality is low in cases such as primary polydipsia, which creates a maximally dilute urine of 40-100 mEq/L, and in tea-and-toast diets or beer potomania due to low solute intake. Urine osmolality can be elevated in hypovolemic states as well as SIADH, and is variable in hypothyroidism and selective serotonin reuptake inhibitor administration. Thus, urine sodium, and not urine osmolality, is the most useful differentiator between SIADH and hypovolemic states.

In a study of 555 patients with hyponatremia secondary to SIADH, mean urine sodium was found to be 72 (range 30-251) and the median urine osmolality was 379 (range 123-1019).⁵

In cases of marked hyperglycemia, serum osmolality should be measured to evaluate hyperglycemia as a cause of hyperosmolar hyponatremia. Pseudohyponatremia in the setting of hyperlipidemia, hypertriglyceridemia, or hyperparaproteinemia represents a laboratory artifact due to lower plasma water concentration in the specimen sample and should be excluded.
 

Hypokalemia

About 20% of patients are hypokalemic during an inpatient hospitalization. There is a broad differential for hypokalemia, including medical, nutritional, and medication-related causes. Exogenous insulin administration or endogenous production in cases of refeeding syndrome drives potassium intracellularly via the N+/K+ ATPase. Increased sympathetic activity from alcohol withdrawal, acute myocardial infarction, head injury, or thyroid imbalance, as well as iatrogenic causes such as albuterol administration, also drive potassium intracellularly. Diarrhea and nasogastric tube suction lead to gastrointestinal (GI) potassium losses, while antibiotics, chemotherapeutic agents, and diuretics can cause hypokalemia through renal potassium wasting. Hyperaldosteronism and renal tubular acidosis are less common causes.⁶

The history, review of medications, physical exam, and initial basic laboratory testing (electrolytes, BUN, creatinine, magnesium) should assess for pseudohypokalemia, poor oral intake, diuretic use, acid-base disturbances, or GI losses.

Measuring urine potassium is useful in the work-up of the hypokalemic patient when these conditions are not evident. Urine potassium – either 24-hour or spot urine potassium-to-creatinine ratio – can help determine if urinary potassium wasting is a factor. Potassium is excreted at a near constant rate throughout the day. A urine potassium-to-creatinine ratio corrects for variations in urine volume. When this ratio is greater than 13 mEq/g, renal potassium losses should be suspected. If the ratio is less than 13 mEq/g, hypokalemia is likely due to transcellular potassium shifts, GI losses, diuretics, or poor intake.

Hyperkalemia

Several concepts in hypokalemia are relevant to hyperkalemia. Redistribution of potassium into the extracellular fluid can cause hyperkalemia when the body tries to counterbalance low extracellular pH by potassium-hydrogen exchange. Medications may cause an extracellular shift of potassium (e.g. digoxin) or induce diminished potassium excretion (e.g. NSAIDs, spironolactone, ACE/ARBs).

CKD and end-stage kidney disease are common causes of hyperkalemia in the hospitalized patient – as functioning nephrons decrease, poor Na-K exchange ensues. Hypoaldosteronism and type 4 renal tubular acidosis are also on the differential diagnosis. Pseudohyperkalemia secondary to thrombocytosis, erythrocytosis, or activated platelets should be considered and evaluated.

Appropriate renal excretion of potassium is mediated by the connecting segment between the distal tubule and the collecting duct, and the cortical collecting duct itself. There are four major causes of hyperkalemia due to reduced urinary potassium secretion: reduced aldosterone secretion, reduced response to aldosterone, reduced distal sodium and water delivery (often related to low effective arterial blood volume), and kidney injury.⁶

Measurement of 24-hour urinary potassium excretion is of limited utility in patients with persistent stable hyperkalemia because urinary potassium excretion is related to potassium intake. The TTKG was previously used to assess the degree of aldosterone activity by estimating the potassium concentration in the cortical collecting tubule. However, some assumptions upon which this calculation was based have been considered invalid by the original studies’ authors, and the TTKG to evaluate potassium abnormalities is no longer uniformly recommended.^7,8 Ultimately, if patients have persistent hyperkalemia, work-up for hypoaldosteronism should be considered.
 

Normal anion gap metabolic acidosis

The urine anion gap (UAG) is used to determine the cause of normal anion gap hyperchloremic metabolic acidosis by indirectly measuring urinary excretion of ammonium. To maintain a normal acid/base balance, hydrogen ions are excreted in the urine with simultaneous reabsorption of bicarbonate. Hydrogen ions are bound to ammonia (NH3) to form ammonium (NH4+), which is excreted as NH4Cl in the urine.

The UAG is calculated by adding urine sodium and urine potassium and subtracting urine chloride (see Table 1). In a patient without an acid/base disturbance, the UAG is positive because more Na and K is absorbed in the gastrointestinal system compared to Cl, and thus more Na and K is excreted in the urine. In a normal anion gap metabolic acidosis through an acid load or bicarbonate loss, the normal response of the kidney is to excrete more hydrogen ions, resulting in more chloride excretion as NH4Cl. This leads to a negative urine anion gap, as Cl excretion outweighs Na and K excretion. When NH4+ excretion is impaired, such as in distal renal tubular acidosis (RTA), the urine anion gap will remain positive despite the metabolic acidosis. Thus, a positive UAG points to renal causes of the normal anion gap metabolic acidosis, whereas a negative UAG points to extrarenal causes such as bicarbonate losses in the GI tract.⁹
 

Additional considerations

Urine studies can also be useful for assessment of proteinuria and albuminuria in a patient with CKD or diabetes, diagnosis of plasma cell dyscrasias, the diagnosis and prevention of nephrolithiasis, and a wide variety of other conditions.

Back to the case

Our patient was admitted with an elevated creatinine of unclear chronicity, and subacute symptoms of uremia. Because she was oliguric, urine and serum sodium and creatinine were measured before intravenous fluids were administered. Her FENa was 2%, which was not consistent with prerenal azotemia or ATN. She was found to have CKD secondary to previously undiagnosed diabetes. Upon further questioning, she had been taking high-dose NSAIDs for her chronic knee pain. Her renal function improved mildly by withholding NSAIDs, and she was discharged with appropriate nephrology follow-up.

Bottom line

Urine electrolytes have specific indications and utilities for different clinical scenarios, and should be ordered in a targeted manner that can aide in diagnosing AKI, hyponatremia, hypokalemia, and normal anion gap metabolic acidosis.

Dr. Tummalapalli, Dr. Krouss, and Dr. Goetz are hospitalists in the department of medicine at the Icahn School of Medicine at Mount Sinai in New York City.

References

1. Brosius FC, Lau K. Low fractional excretion of sodium in acute renal failure: role of timing of the test and ischemia. Am J Nephrol. 1986;6(6):450-7.

2. Gottfried J, Weisen J, Raina R, Nally J. Finding the cause of acute kidney injury: Which index of fractional excretion is better? Cleve Clin J Med. 2012;79(2):121-6.

3. Steiner, RW. Interpreting the fractional excretion of sodium. Am J Med. 1984;77(4):699-702.

4. DeVita MV, Gardenswartz MH, Konecky A, Zabetakis PM. Incidence and etiology of hyponatremia in an intensive care unit. Clin Nephrol. 1990;34(4):163-6.

5. Shepshelovich D, Leibovitch C, Klein A, et al. The syndrome of inappropriate antidiuretic hormone secretion: distribution and characterization according to etiologies. Eur J Int Med. 2015;26(10):819-24.

6. Mount DB. Fluid and Electrolyte Disturbances. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill; 2015.

7. Kamel KS. Intrarenal urea recycling leads to a higher rate of renal excretion of potassium: an hypothesis with clinical implications. Curr Opin Nephrol Hypertens. 2011 Sep;20(5):547-54.

8. Kamel KS, Davids MR, Lin S-H, Halperin ML. Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine. In: Brenner and Rector’s The Kidney, 27, 804-45.e2. Philadelphia, PA: Elsevier; 2016.

9. Goldstein MB, Bear R, Richardson RMA, Marsden PA, Halperin ML. The Urine Anion Gap: a clinically useful index of ammonium excretion. Am J Med Sci. 1986;198-202.

Key Points:

• In acute kidney injury, the FENa and FEUrea may be calculated to distinguish prerenal azotemia from ATN; however, FENa and FEUrea may be low in a wide variety of conditions other than prerenal azotemia.

• Urine sodium and osmolality values are helpful in diagnosing the cause of hyponatremia, but have a number of limitations in nonoliguric patients and those with CKD.

• An elevated transtubular potassium gradient (TTKG) may indicate renal loss of potassium in patients with hypokalemia.

• A positive urine anion gap (UAG) in the setting of a normal anion gap metabolic acidosis points to renal causes of the metabolic acidosis, whereas a negative UAG points to extrarenal causes such as bicarbonate losses in the GI tract.Ad

Additional Reading:

Goldstein MB, Bear R, Richardson RMA, Marsden PA, Halperin ML. The Urine Anion Gap: A Clinically Useful Index of Ammonium Excretion. Am J Med Sci. 1986;198-202.

Gotfried J, Wiesen J, Raina R, Nally Jr JV. Finding the cause of acute kidney injury: which index of fractional excretion is better. Cleve Clin J Med. 2012;79(2):121-126.

Kamel KS, Davids MR, Lin S-H, Halperin ML. Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine. In: Brenner and Rector’s The Kidney, 27, 804-845.e2. Philadelphia, PA: Elsevier; 2016.

The case

A 50-year old woman naive to the health care system presents to the ED with nausea, malaise, and decreased exercise tolerance for several weeks. Physical exam reveals mild bilateral lower extremity edema. Her labs are notable for an elevated creatinine of 7.0. She is admitted for work-up of her renal disease.

Nephrology was consulted and recommended obtaining urine electrolytes. The admitting hospitalist is unsure which urine electrolytes are appropriate to order, and in turn orders all of the urine electrolytes in the order set.

Which urine electrolytes should be ordered in various clinical contexts?
 

Introduction

Hospitalists have been on the forefront of efforts to tailor testing and resource utilization to eliminate wasteful practices in health care. To order and interpret diagnostic tests appropriately, a hospitalist needs to have a thorough understanding of the diagnostic utility of laboratory tests. There is a lack of clear diagnostic guidelines, so ordering all the urine electrolytes in a “blanket” strategy is a common practice. We will discuss the diagnostic utility of each of the urine electrolytes in a variety of clinical scenarios.

Acute kidney injury

Both the fractional excretion of sodium (FENa) and the fractional excretion of urea (FEUrea) have long been used as part of the standard work-up for determining if acute kidney injury (AKI) is due to prerenal causes. Although these markers prove to be beneficial in the work-up of AKI, both the FENa and FEUrea have several limitations.

FENa measures the ratio of sodium excreted in the urine compared to how much is filtered through the kidney. A FENa of less than 1% in oliguric patients may indicate prerenal azotemia, as an increased reabsorption of sodium is the appropriate response of functioning nephrons to decreased renal perfusion. Values greater than 3% may be consistent with acute tubular necrosis (ATN) due to inappropriate sodium excretion in the setting of tubular damage.

Importantly, a FENa value of less than 1% occurs in a number of conditions other than prerenal azotemia due to dehydration, including hypervolemic prerenal states such as cirrhosis or heart failure; AKI due to radiocontrast or heme pigments; acute glomerulonephritis; transition from prerenal to postischemic ATN or sepsis, and in acute interstitial nephritis (AIN).^1,2 Approximately 10% of patients with nonoliguric ATN have a FENa less than 1.0%. Moreover, use of diuretics can falsely elevate the FENa due to inhibition of sodium reabsorption. FENa values above 3% can occur in volume contraction in patients with chronic kidney disease (CKD) or in elderly patients as their sodium reabsorption is impaired.³ Acute volume loss (e.g. blood loss), or more commonly, administration of diuretics or intravenous fluids, can also alter the interpretation of the FENa.²

Hyponatremia

Hyponatremia is the most common electrolyte abnormality in hospitalized patients, with a prevalence of up to 30% in critically ill patients.⁴ It often is acquired during the hospitalization itself. A detailed history and physical exam, including careful assessment of volume status, is as important as laboratory values in establishing the cause of hyponatremia.

Urine sodium and urine osmolality are measured to understand whether the renin-aldosterone-angiotensin system (RAAS) and antidiuretic hormone (ADH) are activated. If renal blood flow or renal delivery of sodium is decreased, renin secretion from the juxtaglomerular apparatus will be activated, ultimately leading to increased reabsorption of sodium in the distal tubules and collecting ducts. Thus, low urine sodium signals that the RAAS is activated due to decreased serum sodium concentration or decreased renal blood flow from hypovolemia or low effective arterial circulation from cirrhosis or heart failure.

Most causes of hyponatremia will have low urine sodium values, including hypovolemia, cirrhosis, heart failure, “tea-and-toast” diet, beer potomania, and primary polydipsia. However, the urine sodium may be unreliable in patients who are not oliguric or who have CKD.

Diuretic-induced hyponatremia from thiazide or loop diuretics will likely have elevated urine sodium levels. Similarly, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) will have an elevated urine sodium above 20-40 mEq/L.

Urine osmolality becomes elevated when ADH is secreted in response to reduced plasma volume or increased plasma osmolality. Urine osmolality is low in cases such as primary polydipsia, which creates a maximally dilute urine of 40-100 mEq/L, and in tea-and-toast diets or beer potomania due to low solute intake. Urine osmolality can be elevated in hypovolemic states as well as SIADH, and is variable in hypothyroidism and selective serotonin reuptake inhibitor administration. Thus, urine sodium, and not urine osmolality, is the most useful differentiator between SIADH and hypovolemic states.

In a study of 555 patients with hyponatremia secondary to SIADH, mean urine sodium was found to be 72 (range 30-251) and the median urine osmolality was 379 (range 123-1019).⁵

In cases of marked hyperglycemia, serum osmolality should be measured to evaluate hyperglycemia as a cause of hyperosmolar hyponatremia. Pseudohyponatremia in the setting of hyperlipidemia, hypertriglyceridemia, or hyperparaproteinemia represents a laboratory artifact due to lower plasma water concentration in the specimen sample and should be excluded.
 

Hypokalemia

About 20% of patients are hypokalemic during an inpatient hospitalization. There is a broad differential for hypokalemia, including medical, nutritional, and medication-related causes. Exogenous insulin administration or endogenous production in cases of refeeding syndrome drives potassium intracellularly via the N+/K+ ATPase. Increased sympathetic activity from alcohol withdrawal, acute myocardial infarction, head injury, or thyroid imbalance, as well as iatrogenic causes such as albuterol administration, also drive potassium intracellularly. Diarrhea and nasogastric tube suction lead to gastrointestinal (GI) potassium losses, while antibiotics, chemotherapeutic agents, and diuretics can cause hypokalemia through renal potassium wasting. Hyperaldosteronism and renal tubular acidosis are less common causes.⁶

The history, review of medications, physical exam, and initial basic laboratory testing (electrolytes, BUN, creatinine, magnesium) should assess for pseudohypokalemia, poor oral intake, diuretic use, acid-base disturbances, or GI losses.

Measuring urine potassium is useful in the work-up of the hypokalemic patient when these conditions are not evident. Urine potassium – either 24-hour or spot urine potassium-to-creatinine ratio – can help determine if urinary potassium wasting is a factor. Potassium is excreted at a near constant rate throughout the day. A urine potassium-to-creatinine ratio corrects for variations in urine volume. When this ratio is greater than 13 mEq/g, renal potassium losses should be suspected. If the ratio is less than 13 mEq/g, hypokalemia is likely due to transcellular potassium shifts, GI losses, diuretics, or poor intake.

Hyperkalemia

Several concepts in hypokalemia are relevant to hyperkalemia. Redistribution of potassium into the extracellular fluid can cause hyperkalemia when the body tries to counterbalance low extracellular pH by potassium-hydrogen exchange. Medications may cause an extracellular shift of potassium (e.g. digoxin) or induce diminished potassium excretion (e.g. NSAIDs, spironolactone, ACE/ARBs).

CKD and end-stage kidney disease are common causes of hyperkalemia in the hospitalized patient – as functioning nephrons decrease, poor Na-K exchange ensues. Hypoaldosteronism and type 4 renal tubular acidosis are also on the differential diagnosis. Pseudohyperkalemia secondary to thrombocytosis, erythrocytosis, or activated platelets should be considered and evaluated.

Appropriate renal excretion of potassium is mediated by the connecting segment between the distal tubule and the collecting duct, and the cortical collecting duct itself. There are four major causes of hyperkalemia due to reduced urinary potassium secretion: reduced aldosterone secretion, reduced response to aldosterone, reduced distal sodium and water delivery (often related to low effective arterial blood volume), and kidney injury.⁶

Measurement of 24-hour urinary potassium excretion is of limited utility in patients with persistent stable hyperkalemia because urinary potassium excretion is related to potassium intake. The TTKG was previously used to assess the degree of aldosterone activity by estimating the potassium concentration in the cortical collecting tubule. However, some assumptions upon which this calculation was based have been considered invalid by the original studies’ authors, and the TTKG to evaluate potassium abnormalities is no longer uniformly recommended.^7,8 Ultimately, if patients have persistent hyperkalemia, work-up for hypoaldosteronism should be considered.
 

Normal anion gap metabolic acidosis

The urine anion gap (UAG) is used to determine the cause of normal anion gap hyperchloremic metabolic acidosis by indirectly measuring urinary excretion of ammonium. To maintain a normal acid/base balance, hydrogen ions are excreted in the urine with simultaneous reabsorption of bicarbonate. Hydrogen ions are bound to ammonia (NH3) to form ammonium (NH4+), which is excreted as NH4Cl in the urine.

The UAG is calculated by adding urine sodium and urine potassium and subtracting urine chloride (see Table 1). In a patient without an acid/base disturbance, the UAG is positive because more Na and K is absorbed in the gastrointestinal system compared to Cl, and thus more Na and K is excreted in the urine. In a normal anion gap metabolic acidosis through an acid load or bicarbonate loss, the normal response of the kidney is to excrete more hydrogen ions, resulting in more chloride excretion as NH4Cl. This leads to a negative urine anion gap, as Cl excretion outweighs Na and K excretion. When NH4+ excretion is impaired, such as in distal renal tubular acidosis (RTA), the urine anion gap will remain positive despite the metabolic acidosis. Thus, a positive UAG points to renal causes of the normal anion gap metabolic acidosis, whereas a negative UAG points to extrarenal causes such as bicarbonate losses in the GI tract.⁹
 

Additional considerations

Urine studies can also be useful for assessment of proteinuria and albuminuria in a patient with CKD or diabetes, diagnosis of plasma cell dyscrasias, the diagnosis and prevention of nephrolithiasis, and a wide variety of other conditions.

Back to the case

Our patient was admitted with an elevated creatinine of unclear chronicity, and subacute symptoms of uremia. Because she was oliguric, urine and serum sodium and creatinine were measured before intravenous fluids were administered. Her FENa was 2%, which was not consistent with prerenal azotemia or ATN. She was found to have CKD secondary to previously undiagnosed diabetes. Upon further questioning, she had been taking high-dose NSAIDs for her chronic knee pain. Her renal function improved mildly by withholding NSAIDs, and she was discharged with appropriate nephrology follow-up.

Bottom line

Urine electrolytes have specific indications and utilities for different clinical scenarios, and should be ordered in a targeted manner that can aide in diagnosing AKI, hyponatremia, hypokalemia, and normal anion gap metabolic acidosis.

Dr. Tummalapalli, Dr. Krouss, and Dr. Goetz are hospitalists in the department of medicine at the Icahn School of Medicine at Mount Sinai in New York City.

References

1. Brosius FC, Lau K. Low fractional excretion of sodium in acute renal failure: role of timing of the test and ischemia. Am J Nephrol. 1986;6(6):450-7.

2. Gottfried J, Weisen J, Raina R, Nally J. Finding the cause of acute kidney injury: Which index of fractional excretion is better? Cleve Clin J Med. 2012;79(2):121-6.

3. Steiner, RW. Interpreting the fractional excretion of sodium. Am J Med. 1984;77(4):699-702.

4. DeVita MV, Gardenswartz MH, Konecky A, Zabetakis PM. Incidence and etiology of hyponatremia in an intensive care unit. Clin Nephrol. 1990;34(4):163-6.

5. Shepshelovich D, Leibovitch C, Klein A, et al. The syndrome of inappropriate antidiuretic hormone secretion: distribution and characterization according to etiologies. Eur J Int Med. 2015;26(10):819-24.

6. Mount DB. Fluid and Electrolyte Disturbances. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill; 2015.

7. Kamel KS. Intrarenal urea recycling leads to a higher rate of renal excretion of potassium: an hypothesis with clinical implications. Curr Opin Nephrol Hypertens. 2011 Sep;20(5):547-54.

8. Kamel KS, Davids MR, Lin S-H, Halperin ML. Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine. In: Brenner and Rector’s The Kidney, 27, 804-45.e2. Philadelphia, PA: Elsevier; 2016.

9. Goldstein MB, Bear R, Richardson RMA, Marsden PA, Halperin ML. The Urine Anion Gap: a clinically useful index of ammonium excretion. Am J Med Sci. 1986;198-202.

Key Points:

• In acute kidney injury, the FENa and FEUrea may be calculated to distinguish prerenal azotemia from ATN; however, FENa and FEUrea may be low in a wide variety of conditions other than prerenal azotemia.

• Urine sodium and osmolality values are helpful in diagnosing the cause of hyponatremia, but have a number of limitations in nonoliguric patients and those with CKD.

• An elevated transtubular potassium gradient (TTKG) may indicate renal loss of potassium in patients with hypokalemia.

• A positive urine anion gap (UAG) in the setting of a normal anion gap metabolic acidosis points to renal causes of the metabolic acidosis, whereas a negative UAG points to extrarenal causes such as bicarbonate losses in the GI tract.Ad

Additional Reading:

Goldstein MB, Bear R, Richardson RMA, Marsden PA, Halperin ML. The Urine Anion Gap: A Clinically Useful Index of Ammonium Excretion. Am J Med Sci. 1986;198-202.

Gotfried J, Wiesen J, Raina R, Nally Jr JV. Finding the cause of acute kidney injury: which index of fractional excretion is better. Cleve Clin J Med. 2012;79(2):121-126.

Kamel KS, Davids MR, Lin S-H, Halperin ML. Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine. In: Brenner and Rector’s The Kidney, 27, 804-845.e2. Philadelphia, PA: Elsevier; 2016.