Hippocratic Medicine No. 5: The Heart of the Matter

It’s 7PM, and you are coming onto a busy 12-hour overnight shift. Your first patient is a 57-year-old African American female, Mrs. S., with a past medical history of hypertension. She is there with left sided chest pain intermittently present for the last 7-10 days that is not exertional, and not associated with any other symptoms. It lasts anywhere from minutes to an hour. She was evaluated for this pain last week, and a pulmonary embolism work-up was negative. She was discharged home with diagnosis of Left Pectoralis Muscle Strain. Her vital signs and exam are normal except for reproducible chest pain along the left rib margin. Her EKG demonstrates a normal sinus rhythm, and her first troponin is negative.

You decide to pursue a cardiac work-up with serial troponins and a cardiac stress echocardiogram. The patient is surprised because she has never been told she has high cholesterol, diabetes, or that she is otherwise at risk for atherosclerotic heart disease, but she agrees with this plan. While several risk stratification tools such as the Thrombosis in Myocardial Infarction (TIMI) risk score and Global Registry of Acute Coronary Events (GRACE) have been developed, they have not been sensitive enough to rule out Acute Coronary Syndrome (ACS) in ED patients [1, 2]. The HEART score (see table below) is a decision aid used to risk-stratify patients with a score that is interpreted on a range from low to high-risk for Major Adverse Cardiac Events (MACE). A cohort study by Mahler et al in the U.S. found a rate of MACE in 0.6% of 1070 patients presenting the ED with chest pain deemed to be low-risk by HEART score [2]. Mrs. S had a HEART score of 2, and would have been deemed low risk.

Mrs. S was amenable to the plan of further cardiac evaluation. However, if she was told she was low risk and given the option to follow up as an outpatient, would she have opted for this instead? Hess et al conducted a prospective, randomized study in which patients were given a pictograph and allowed to make this decision (see figure below). Compared to patients that received usual care (MD decision for ACS work up), those given the pictograph demonstrated better knowledge of their ACS risk, participated more in decision making, and opted less often to be admitted for further cardiac evaluation. Of note, there were no adverse cardiac events in either group [3].

Three days later, you notice that Mrs. S is still an inpatient. She had a positive stress test and subsequently underwent a cardiac catheterization that was negative for any significant coronary vessel disease. Post catheterization, Vascular Surgery was consulted because she had unfortunately developed a femoral artery pseudoaneurysm. Femoral artery vascular complications such as pseudoaneurysm and hematomas occur in up to 6% of cases, and other complications include dissection, thrombosis and infection [4,5,6].

The Coronary Artery Surgery Study (CASS) found that the pretest probability of coronary artery disease (CAD) varied between 5% and 89% based on age, sex, and chest pain characteristics [7].  Risk factors for CAD include chest pain consistent with angina, age, gender, history of diabetes or hyperlipidemia, and smoking. The current American College of Cardiology/American Heart Association guidelines for stress testing recommend assessment with an imaging modality (i.e. stress ECHO) for patients that are at intermediate risk for CAD. Any of the following factors suggests an intermediate risk: Prior history of CAD, ECG with ST-segment depression 0.05 to <0.10 mV and/or flat or inverted T waves <0.20 mV deep, diabetes mellitus, chronic kidney disease, and advanced age [8, 9, 10, 11].

With the rising costs of healthcare in the U.S., the American College of Physicians has called for more judicious use of screening and diagnostic tests. One principle they emphasize is that when the pretest probability of disease is low, the likelihood of a false positive test result is higher than a true positive test result [12].  Namely, cardiac stress testing in patients that are low risk for CAD is not recommended because the low pretest probability of this study in this population leads to subsequent higher likelihood for false positives and increased needless downstream interventions with their own rates of harm. Of note, the inverse is also true; those with a very high pretest probability are more likely to have a false negative result. Moreover, a retrospective study in 2013 by Foy et al demonstrated that out of 2662 patients without a history of CAD that had a cardiac catheterization, 866 were preceded by a stress imaging, with a pretest probability of 18% PPV for stress echocardiogram, and 27% for single-photon emission computed tomography. While this study is limited by the biases inherent to a retrospective study, it does suggest that too many stress tests are currently being ordered on low risk patients [13].

Mrs. S was low risk by her HEART score of 2 and had a low pretest probability for CAD based on the data from the CASS study, and was therefore at higher risk for a false positive result with cardiac stress testing. Furthermore, the downstream testing as a result of a positive stress test puts patients at risk for adverse events due to the invasive nature of cardiac catheterization and its complications. Mrs. S intuitively suspected that her risk for CAD was low, and as her physicians we should have easily and accurately made that assessment ourselves. As demonstrated by Hess et al, a better approach would have been to engage the patient in shared decision-making, which would have given her input into the management plan, and likely avoided this complication. While some physicians aim to reduce medico-legal liability by ruling out ACS with a stress test, our patients are exposed to over testing and even injury when this test is used indiscriminately. The cardiac stress test is to be used as a diagnostic tool in the correct clinical context, and a false positive result in a patient with a low pretest probability of disease may not only lead to complications, but also could have been determined without the test altogether.

Submitted by Aldo Andino, PGY-3

Peer Reviewed by Alicia Oberle, PGY-4

Faculty Reviewed by Douglas Char
Professor, Emergency Medicine, Washington University School of Medicine


[1] Emerg Med J. 2014 Apr;31(4):281-5. doi: 10.1136/emermed-2012-201323. Epub 2013 Apr 10.
[2] Crit Pathw Cardiol. 2011 Sep;10(3):128-33.
[3] Circ Cardiovasc Qual Outcomes. 2012 May;5(3):251-9.
[4] Am J Cardiol. 1992;69(1):63.
[5] Am J Cardiol. 1993;72(13):47E.
[6] Circulation. 1993;88(4 Pt 1):1569.
[7] N Engl J Med. 1979;301:230-235.
[8] J Am Soc Echocardiogr. 2011 Mar;24(3):229-67. doi: 10.1016/j.echo.2010.12.008.
[9] J Am Coll Cardiol. 2002;40(8):1531.
[10] Circulation. 2009;119:e561-e587.
[11] J Am Soc Echocardiogr. 2011 Mar;24(3):229-67.
[12] Ann Intern Med. 2012 Jan 17;156(2):147-9.
[13] Am J Med Qual. 2014 Mar-Apr;29(2):153-9


The Hippocratic Medicine series is modeled after the Do No Harm project pioneered at the University of Colorado. The aim of this series is to raise awareness about the avoidance of avoidable care i.e. for how medical overuse has the potential to do patient harm. Because every test or intervention we do has the potential for not just benefit but also harm, we should seek that our patients do better because of the care we provide instead of despite it. The WUSM Hippocratic Medicine Series is supported by a grant provided by the Foundation for Barnes Jewish Hospital.

Hippocratic Medicine No. 4: Victims of Our Own Success?

Clinical Scenario:
Working a emergency department shift on a typical busy day, you see the next patient slotted is a 36-year-old female coming in with shortness of breath and fatigue. She also has a history of anemia, anxiety, and panic disorder.

About one month prior, she presented to another emergency department (ED) complaining of chest pain for the last several weeks along with other vague complaints. Her heart rate of 101 prevented application of the PERC rule and made her moderate risk by Well’s criteria. A d-dimer was sent and was elevated, so she underwent a computed tomography pulmonary angiography (CTPA) scan looking for pulmonary embolism (PE). This demonstrated non-occlusive pulmonary emboli present in branches of the left upper lobe, right middle lobe, and left lower lobe pulmonary arteries. She was admitted to the hospital and started on rivaroxaban.

About 2 weeks prior to today’s visit, she had presented with continued chest pain and shortness of breath. She underwent another CTPA demonstrating no pulmonary emboli. Her hemoglobin was checked on this visit and found to be 11 g/dl. She was discharged and continued taking her rivaroxaban.

During to today’s visit, in addition to her shortness of breath and fatigue, she is also complaining of vaginal bleeding. It is around the normal time for menses, however it has been going on longer and heavier than usual. Her hemoglobin is checked and is found to be 5.6 g/dl. She is given two units of packed red blood cells and admitted to the hospital.

You can’t help but wonder, was there truly a PE in the first place? Did it require treatment? Did we cause this patient harm by putting her on anticoagulation?

Literature review:

The diagnosis of PE has evolved significantly over the past few decades from a disease only suspected and confirmed on autopsy to small subsegmental pulmonary embolisms (SSPE) found on multi-detector CTPA. Despite the increased diagnosis of PE due to CTPA, there has not been a significant change in associated mortality nor an increase in diagnosis of larger, central pulmonary emboli [2]. What has changed is the increased diagnosis of smaller sub-segmental pulmonary embolism (SSPE) due likely to both the sensitivity of the technology and increased physician vigilance for finding the disease [1].

Not long ago, pulmonary embolism was felt to be under-diagnosed, only found after the patient had died from the condition. With the widespread availability and ease of CTPA, there is increasingly concern for overuse of CTPA, perhaps with associated over-diagnosis and over-treatment. Wiener et al studied the incidence, mortality, and treatment complications of PE in the 5 years preceding the introduction of CTPA and the years that followed [2]. With the introduction of CTPA, he found that the diagnosis of PE almost doubled (62.1 to 112.3 per 100,000) and complications from anticoagulation increased (3.1 to 5.3 per 100,000), while the mortality from PE stayed about the same (12.3 to 11.9). While the increase in diagnosis is probably due to increased awareness of PE as well as availability of testing, some of the increase may also be due to the detection of smaller SSPE on multi-detector CTPA that may not be clinically relevant [3].

As a large proportion of the additional PEs detected (above the prior baseline) are SSPEs [3], and in light of the increase in bleeding complications from anticoagulation, this raises the question as to whether the risks of treatment outweigh the risks of going untreated. A study in CHEST demonstrated that hemodynamically stable patients with segmental or sub-segmental PE had low risk of adverse outcome, although in this study population treatment was at the discretion of the treating physician [6]. In a review paper by Ikesaka and Carrier, they found that patients with suspected PE with a non-diagnostic ventilation-perfusion scan and negative compression ultrasonography of the lower extremities could be safely managed without the use of anticoagulation with a recurrent risk of embolism similar to those without PE on CTPA [1]. In addition, 17% of patients with a low probability ventilation/perfusion (V/Q) scan had an isolated SSPE on CTPA.

Despite many physicians treating it otherwise, CTPA is not a gold standard for PE diagnosis. Up to 11% of CTPA studies read initially positive for SSPE are read as negative when reviewed by experienced thoracic radiologist. These 'false positives' may be caused by indeterminate intra-luminal filling defects that may be caused by patient motion artifact or other imaging artifact [4,7].

In addition to the potential harm in placing someone unnecessarily on anticoagulation, testing for PE can also cause harm. The radiation from the scan can cause promote cancer later in the patient’s life while the contrast can induce nephropathy. In a conservative estimate by Newman and Schriger, they found that in testing for PE, physicians can prevent 6 deaths from PE and 24 major, nonfatal PE events per 10,000 individuals [8]. At the same time, testing also can cause 36 deaths and 37 nonfatal major medical harms per 10,000 from bleeding complications, development of cancer, and contrast-induced nephropathy. This estimates seems to imply that physicians can cause more harm than benefit in testing for PE if the diagnostic test is not applied judiciously to patients.

With the introduction of CTPA, there has been a substantial increase in the diagnosis of PE, especially SSPE, without much apparent clinical benefit with treatment. Are we over-diagnosing more patients and putting them on treatments with potential harm? Do we need to scan or even treat these patients? In this presented case, did this patient truly have a PE given that a repeat scan 2 weeks later was read as completely negative? Did this patient bleed down to a hemoglobin of 5.6 g/dl because of the treatment she was on? 

Take home points:
- Pulmonary embolism may be over-diagnosed and over-treated
- Be aware of the false positive rate with CTPA and consider this when deciding whom to test
- There’s evidence to suggest not all PE’s are the same, but there is insufficient ED-based data to determine who should receive anticoagulation
-Realize that you can cause harm putting a patient on anticoagulation when it is not necessarily needed

Submitted by Steven Hung, PGY-2 (@docHungER)
Edited by Alicia Oberle, PGY-3
Faculty Reviewed by Ryan Schneider, Richard Griffey, and Chris Carpenter (@SAEMEBM)
Image by Maia Dorsett (@maiadorsett)

Want to read more? Click here to read the WashU Journal Club on reducing PE protocol CT ordering rates in the ED.

1. Ikesaka F, Carrier M. Clinical significance and management of sub-segmental pulmonary embolism. J Thromb Thrombolysis. 2015 Apr;39(3):311-4.
2. Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831-837
3. Carrier M, Righini M, Wells PS, Perrier A, Anderson DR, Rodger MA, Pleasance S, Le Gal G. Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies. J Thromb Haemost. 2010 Aug;8(8):1716-22.
4. Jones SE, Wittram C. The indeterminate CT pulmonary angiogram: imaging characteristics and patient clinical outcome. Radiology. 2005 Oct;237(1):329-37.
5. Prasad V, Rho J, Cifu A. The diagnosis and treatment of pulmonary embolism: a metaphor for medicine in the evidence-based medicine era. Arch Intern Med. 2012 Jun 25;172(12):955-8.
6. Vedovati MC, Becattini C, Agnelli G, Kamphuisen PW, Masotti L, Pruszczyk P, Casazza F, Salvi A, Grifoni S, Carugati A, Konstantinides S, Schreuder M, Golebiowski M, Duranti M. Multidetector CT scan for acute pulmonary embolism: embolic burden and clinical outcome. Chest. 2012 Dec; 142(6):1417-24.
7. Wittram C, Maher MM, Yoo AJ, Kalra MK, Shepard JA, McLoud TC. CT angiography of pulmonary embolism: diagnostic criteria and causes of misdiagnosis. Radiographics. 2004 Sep-Oct;24(5):1219-38.
8.Newman DH, Schriger DL. Rethinking testing for pulmonary embolism: less is more. Ann Emerg Med. 2011 Jun;57(6):622-627.e3.

The Hippocratic Medicine series is modeled after the Do No Harm project pioneered at the University of Colorado. The aim of this series is to raise awareness about the avoidance of avoidable care i.e. for how medical overuse has the potential to do patient harm. Because every test or intervention we do has the potential for not just benefit but also harm, we should seek that our patients do better because of the care we provide instead of despite it. The WUSM Hippocratic Medicine Series is supported by a grant provided by the Foundation for Barnes Jewish Hospital.

Hippocratic medicine No. 3: A Prescription for Honesty, Conversation and Compassion

Clinical Scenario: You are taking care of a middle-aged female who was brought to the emergency department by her family for altered mental status.  She has stage IV ovarian cancer and is undergoing chemotherapy which has caused persistent nausea, vomiting, and diarrhea.  According to her husband, she was conversant and fully oriented this morning.  During the day, she suddenly became very confused.  Per the patient’s husband, the patient has had multiple episodes like this in the past, usually associated with electrolyte abnormalities in the context of her persistent poor PO intake.  You review the patient's electronic chart and note that she has been admitted approximately every two weeks for electrolyte replacement over the course of the last several months.  You call the patient's oncologist, who states that they had been trying to manage her as an outpatient, but agrees that she needs admission again.  You inform the husband of this plan, and he notes, reluctantly, that he is "used to the routine.

It takes a while to get the bed upstairs.  In the meantime, you correct the patient's electrolytes and her mentation improves.  When you go in to check on her, you assess the patient's understanding of her disease.  The patient and her husband are aware of her poor prognosis from cancer, but they are considering another round of chemotherapy and seem resigned to continued aggressive medical interventions.

Despite the busy ED around you, you take time to talk to them about their life.  The patient says that what she actually wants to do is spend as much time at home as possible.  The patient and her husband are not familiar with hospice care and state that she is not ready to "just give up and die."

After your conversation, you walk away and wonder what is (and what should be) the role of emergency providers in initiating end of life conversations with patients and families?  What are the harms of avoiding these difficult subjects and what benefits can be gained by doing so? 

Literature Review:
"End-of-life" is not a rarity in emergency medicine.  Before starting in this field, many of us may have assumed naively that our experience with end-of-life situations would come acutely in the form of sudden cardiac arrests, terrible car accidents, or  gun shot wounds to the chest.  The reality, however, is that emergency medicine also encompasses oncology, geriatrics, end-stage organ failure, debilitating co-morbidities, and social work nightmares.  We take care of the chronically (and newly chronically) ill, and it is our duty as physicians to discuss their medical options with them in a way that they can understand.

The majority of people would prefer to die at home [1,2].  Despite this, over 75% of Americans die in an institution [3].   One in five Americans dies in or soon after a stay in the ICU[4].  In a study done by Teno et al. looking at over 1500 patients who were at the end of life,  67% ended up in a nursing home or hospital [5].  Even for those who go to hospice, the option may be offered late, as many patients die within days (not months) of starting hospice. 

Studies have also shown that we spend more money in a patient’s last 6 months of life than at any other point in their life [2]. States that have had more emphasis on end of life support tend to have fewer ICU days in the last 6 months per the CDC analysis (ranging from 1.6 to 4.3 ICU days). La Crosse, Wisconsin is well known for starting Respecting Choices, a program which encourages participation in end of life discussions and advance directive cares. A Dartmouth program compared the amount of money spent in the last 6 months by patients living in La Crosse, WI to averages across the country and noted that the money spent in the last 6 months in La Crosse was significantly less [6]. 

Aggressive care for the dying is more than an issue of monetary cost in an already-strapped healthcare system.  When studied in two separate populations of patients with metastatic cancer, aggressive care for the dying was associated with reduced quality of life at its end, and worse bereavement adjustment in caregivers [7,8].  End-of-life discussions have been shown to reduce both the incidence of aggressive intervention and the subsequent psychological stress amongst surviving family members[7]. 

In addition, good end-of-life care has been shown to benefit both quality and quantity of life in the terminally ill.  The goals of hospice care are to alleviate suffering and promote the best quality of life for patients and families facing a  prognosis of six months (not days) or less.  Of those admitted to hospice, family members perceived a significant increase of emotional support and respect for their dying loved one. (96% compared to 68%) [5]. Family members were more satisfied with the overall quality of care with hospice services, rating hospice services “excellent” 70% of the time compared to those admitted to the institution setting (less than 50% “excellent” ratings).   According to a 2007 retrospective chart review of Medicare records, patients with CHF, lung cancer, and pancreatic cancer who received hospice care had an increased length of survival (29 days for hospice patients with) when compared with patients who did not [9]. 

Perhaps most importantly, we should consider what constitutes a “good death.”  Zhang et al performed a prospective, longitudinal cohort study of 396 advanced cancer patients and their  caregivers to try and assess what constitutes quality of life at the end of life. They found the factors that were associated with the highest quality of life were fewer hospitalizations, fewer ICU stays, meditation, and therapeutic alliance with their physicians [10]. 

Good end-of-life decisions require honest discussion of goals, but this can be difficult.  Multiple studies have shown that physicians often avoid these conversations [6], and patients may be overly optimistic about their family members understanding of their wishes [2].  Advanced care planning and better communication surrounding end-of-life has the potential to improve patient care.   For example,  Detering et. al. carried out a prospective randomized controlled study of 309 adults over the age of 80  looking at the effect of advance care planning support versus standard care [11]. Of the 56 patients who died within the 6 month study period, those in the advance care planning support group were much more likely to have end of life wishes known (86% vs 30%). in addition, both patients and family of the intervention group had significantly less stress, anxiety, and depression than control group.

Most studies looking at end-of-life communication have been based in the outpatient or ICU setting.  However, we as emergency providers must ask ourselves what role we should play in this process. End of life discussions in the ED, especially for the chronically ill, can be challenging, but like it or not, they occur.  It can be frustrating to talk to a patient with an advanced cancer diagnosis who seems unaware of her prognosis.  How does one get the medical story, communicate with the primary care provider and oncologist, and then talk with the patient and family, all while adhering to the demanding ED timetable?   In the busy ED, it is often easier to avoid such problems than to address them.  However, an abundance of research has demonstrated that an honest and compassionate conversation about goals of care, even if brief,  may be the most beneficial thing that we as an emergency physician can provide to these patients. 

According to the Choosing Wisely campaign "Top Ten" for Emergency Medicine, we should not delay palliative or hospice services for patients who are likely to benefit:

In many cases, for patients whose goal is to be comfortable and avoid hospitalization, hospice care at home can be arranged directly from the emergency department.   For patients who require more care than they can receive at home, an admission may be warranted, but starting a conversation about goals in the ED can smooth the transition.  According to 2012 statistics from the Center to Advance Palliative Care, almost 2/3 of hospitals in the US with more than 50 beds have inpatient palliative care services, and there were over 3500 hospice agencies throughout the US [https://www.capc.org]  .  Emergency physicians should be aware of the resources  available in their area.  For our own hospital, BJH in St. Louis, information about hospice and home care services can be found at the  BJC Hospice website. 

Take home points:  While many people express a desire to die at home, the majority of Americans die in acute or extended care facilities.  The US has a robust system for helping people access aggressive medical care in emergency situations.  This is a tremendous asset for many Americans, but for those dying of serious illness, it may not be the best pathway.  When aggressive care is seen as the default option for dying patients, it may confer significant harm in the form of decreased quality of life and increased long term psychological stress on caregivers.  Despite the pressures of working in the ED,  emergency physicians are well-positioned to help patients, families, and our colleagues in other areas of healthcare begin conversations addressing end-of-life care.    

Submitted by Melissa Kroll (@misskrll) PGY-2
Edited by Maia Dorsett (@maiadorsett)
Faculty reviewed by Maria Dans (Palliative Care) and Douglas Char and Ryan Schneider (Emergency Medicine)

[1] Field, M. J., & Cassel, C. K. (2010). Approaching death: improving care at the end of life. Palliative Care: Transforming the Care of Serious Illness, 79.
[2] Halpern, S. D. (2012, August). Shaping end-of-life care: behavioral economics and advance directives. In Seminars in respiratory and critical care medicine (No. 33, pp. 393-400).
[3] Health, United States. 2010. With special features on death and dying. National Center for Health Statistics [on-line]. Available at www.cdc.gov/nchs/data/hus/hus10.pdf Accessed February 13, 2014.
[4] Angus, D. C., Barnato, A. E., Linde-Zwirble, W. T., Weissfeld, L. A., Watson, R. S., Rickert, T., ... & Robert Wood Johnson Foundation ICU End-Of-Life Peer Group. (2004). Use of intensive care at the end of life in the United States: An epidemiologic study*. Critical care medicine, 32(3), 638-643.
[5]Teno JM, Clarridge BR, Casey V, et al. Family perspectives on end-of-life care at the last place of care. JAMA. 2004;291:88–93.
[6] The Dartmouth Atlas of Health Care. The Dartmouth Institute for Health Policy and Clinical Practice [on-line]. Available at http://www.dartmouthatlas.org/ Accessed February 13, 2014.
[7]Wright, A. A., Zhang, B., Ray, A., Mack, J. W., Trice, E., Balboni, T., ... & Prigerson, H. G. (2008). Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment. Jama, 300(14), 1665-1673.
[8]Wright, A. A., Keating, N. L., Balboni, T. A., Matulonis, U. A., Block, S. D., & Prigerson, H. G. (2010). Place of death: correlations with quality of life of patients with cancer and predictors of bereaved caregivers' mental health. Journal of Clinical Oncology, JCO-2009.
[9] Connor, S. R., Pyenson, B., Fitch, K., Spence, C., & Iwasaki, K. (2007). Comparing hospice and nonhospice patient survival among patients who die within a three-year window. Journal of pain and symptom management, 33(3), 238-246.
[10] Zhang B, Nilsson ME, Prigerson HG. Factors important to patients' quality of life at the end of life. Arch Intern Med. 2012 Aug;172(15):1133-42. 
[11] Detering KM, Hancock AD, Reade MC, et al. The impact of advance care planning on end of life care in elderly patients: Randomised controlled trial. BMJ. 2010;340:c1345. 
 The Hippocratic Medicine series is modeled after the Do No Harm project pioneered at the University of Colorado, the aim of this (hopefully) monthly installment will be on the avoidance of avoidable care i.e. raising awareness for how medical overuse has the potential to do patient harm.   Because every test or intervention we do has the potential for not just benefit but also harm, we should seek that our patients do better because of the care we provide instead of despite it.  The WUSM Hippocratic Medicine Series is supported by a grant provided by the Foundation for Barnes Jewish Hospital. 

Hippocratic Medicine No. 2: Between a Rock and a Hard Place

Clinical Scenario:
You are working in the emergency department on a typical busy day. There are fifteen boarding patients waiting for their bed upstairs, another thirty-plus in the waiting room.  You walk into a room to assess a 75 yo female with confusion. Family says that she has been confused: forgetting to put on one shoe, unable to finish her crossword puzzles, and no longer able to bowl without throwing a gutter ball. Amazingly, the urinalysis is negative. Concerned that she may have had a subacute stroke, you order a head CT without contrast which shows “a large amount of vasogenic edema concerning for neoplasm.” The radiologist recommends a follow up MRI for further evaluation. The consulting neurologist instead asks for a Head CT (HCT) with contrast, reasoning they would not be the admitting service if the patient is found to have a mass. Neurosurgery recommends an MRI to evaluate for a suspected mass, and you learn that it will be 8 hours before the patient can go to MRI. With the pressure of the waiting room, the full rooms, and the boarding patients in the ED, you reluctantly order the HCT with contrast, which shows a right parietal neoplasm. Having rarely, if ever, ordered HCT with contrast, you ask- What are the indications for HCT with contrast in a patient with subacute onset of focal neurological deficits?

Literature Review:
The American College of Radiology (ACR) publishes evidence-based guidelines to help direct the efficacious use of radiologic studies. Their 2012 Appropriateness Criteria for Focal Neurologic deficits discusses the use of HCT vs. MRI. HCT without contrast is recommended for initial evaluation in this case. While contrast can provide additional information, “some pathology is difficult to visualize with CT under any circumstances,” and “MRI is more sensitive than CT for detecting primary and secondary brain lesions and for defining extent of disease.” Additionally, MRI spares the patient exposure to ionizing radiation and “provides information that…approaches the accuracy of a neuropathologic diagnosis” [1].  Specifically, for our patient with subacute onset of neurological deficits, the ACR recommends a HCT without contrast for acute screening. The highest rated imaging for further evaluation is an MRI head with and without contrast, rated an 8/9 for “usually appropriate.” A HCT with contrast was rated a 4/9, for “may be appropriate,” with the typical indication being inability to get an MRI. This patient had no contraindications to MRI and should not have had the contrasted HCT. Eight hours later she had a MRI to more appropriately plan her operative course. 

The Lancet covered the Pitfalls in the Diagnosis of Brain tumors, and lists several elements that indicate a non-neoplastic diagnosis: young adults, recent travel, sexual risk behavior, IV drug addiction, TB, immunosuppression [2]. Some non-neoplastic tumor lesions are abscesses, vascular lesions, or infectious which can be better evaluated with HCT with contrast. Our patient had none of these risk factors.

Reflecting on these guidelines and indications for imaging, the head CT with contrast should not have been ordered for this patient before the MRI. While the non-contrast HCT identified a neoplasm, more definitive testing in the form on an MRI was still required. The HCT with contrast only expedited the patient’s disposition from the ED, yet it added minimally to her care and increased her risk for contrast-induced nephropathy and exposed her to risk of allergic reaction.

So why did the HCT with contrast get ordered? The junior consulting neurologist, the ED attending, radiology and the ED resident (myself) all knew it was an inappropriate next test. For the neurologists, they saw potential harm in an additional handoff of the patient to yet another team (in this case, neurosurgery).  Neurology’s concern was not wrong. Medical error because of a poor handoff is the third most common reason for adverse events leading to patient harm in hospitals [3]. From my perspective as the ED resident, there were multiple perceived harms. For my patient, I saw potential harm for her in staying in the emergency department. She would remain on a gurney, in a curtain-partitioned room, where the next gunshot victim or cardiac arrest would be resuscitated next to her. She would not rest, her home medications were likely to be lost in the shuffle, and the bathroom was further away increasing the risk of falls. She would be at increased risk for delirium. As Aminzadeh found in the study, "Older Adults in the Emergency Department" [4], the longer ED stay the greater number of diagnostic tests performed creating higher risk for adverse outcomes. Most EDs do not have an environment that follows new geriatric ED guidelines [5].  Stuck between ordering a likely unnecessary test with potential for harm and exposing the patient to a prolonged ED stay and patient hand off with their associated risks, we chose by physician gestalt the lesser of two evils.

But in truth, there was more to it than just the calculated risks and benefits for my patient alone.  The prolonged ED stay for my patient also conferred potential harms for the patients  still waiting to be seen in our overcrowded waiting room.  According to the Institute of Medicine report, "On Hospital-Based Emergency Care: At the Breaking Point", 70% of urban emergency departments go on diversion at some time during the year. In 2003, ambulances were diverted 501,000 times, almost once a minute [6].  Our hospital, Barnes-Jewish, operates at 100% capacity more than half the time.  ED overcrowding was found to contribute to 31% of sentinel events. 29 of 55 sentinel events were due to delays in care occurred in emergency department [7].  ED overcrowding is attributed to boarding patients, where “output”- transferring patients to their inpatient bed- is held up. My patient had become an “output” problem: she had an inpatient ready bed but no team willing to take her for 8 hours until an MRI was complete. My fix for this output issue was the unnecessary, potentially harmful HCT with contrast to get her upstairs 6 hours sooner. Length of boarding time has been associated with higher mortality- 2.5% mortality for boarding time < 2hours, and 4.5% for boarding time >12 hours(8). While I recognized the potential harm to my patient, I ordered the test thinking of other harms to my patient and patients I had not yet seen. How do we know which is greater?  The harm of an unnecessary head CT with contrast in one patient or the harm in delaying care for others?  While the squables of establishing an admitting team may be specific to academic centers, the issues of advocating for inpatient admission, transferring to higher level of care, or managing ED throughput are not.  All along the way to doing the right thing, EM physicians can get caught between a rock and a hard place.

What are the solutions to this problem? Moskop, et al. proposed a number of "throughput solutions" to this problem, including disposition lounges and bed management planning teams [7].   Some of these are already used in our system.  We could adopt an “admission pending unit” where admitted patients await testing when the inpatient unit is full [9]. Utilizing a “full-capacity protocol”- moving boarding patients to inpatient hallways throughout the hospital- can ease the burden on the ED and distribute patients to all care areas. Our hospital could also adopt a practice of “smoothing”, which uses data about predictable weekly demands for admissions from the ED (ie Monday afternoon), to spread elective surgeries to other days of the week [9].

Clinical Take home: 

In emergency medicine, we are often stuck between a rock and a hard place when we are just trying to do the right thing by our patients.  When faced with these challenges, we can continue to be patient advocates by:
       - Referring to the American College of Radiology Appropriateness Criteria when considering patient imaging. A great evidence based resource for all radiology studies. http://www.acr.org/Quality-Safety/Appropriateness-Criteria
     - Respecting our elders! Consider the needs of your geriatric patient in the ED    

     - Remembering that boarding times, limitations, and diversion lead to increased mortality
     - Working with our specialists to facility inpatient admission
     - Promoting Full Capacity protocols, and Smoothing which can alleviate the burden of ED     overcrowding and likely save lives.

Submitted by Alicia Oberle, PGY-3
Edited by Maia Dorsett (@maiadorsett), PGY-3
Faculty Reviewed by Douglas Char, Ryan Schneider, and Rob Poirier

The WUSM Do No Harm Project is supported by a grant provided by The Foundation for Barnes Jewish Hospital

1. Wippold FJ, Cornelius RS, Aiken AH, et al. Expert Panel on Neurologic Imaging: Focal Neurological Deficit. American College of Radiology Appropriateness Criteria. 2012.
2. Omuro AM, Leite CC, Mokhtari K, Delattre JY. Pitfalls in the diagonosis of brain tumors. The Lancet. Neurology. 2006 Nov; 5(11):937-48.
3. Jagsi R, Kitch CT, Weinstein EG, et al. Residents report on adverse events and their causes. Archives of Internal Medicine. 2005 Dec 12-26; 165(22): 2607-13.
4. Aminzadeh F, Dalziel WB. Older adults in the emergency department: A systematic review of patterns of use, adverse outcomes, and effectiveness of interventions.
5. Carpenter CR, Bromley M, Caterino JM, et al. Optimal older adult emergency care: introducing multidisciplinary geriatric emergency department guidelines from the American College of Emergency Physicians, American Geriatrics Society, Emergency Nurses Association, and Society for Academic Emergency Medicine. Academic Emergency Medicine. 2014 July; 21(7): 806-809.
6. Institute of Medicine " Front Matter ." Hospital-Based Emergency Care: At the Breaking Point . Washington, DC: The National Academies Press, 2007 .
7. Moskop JC, Sklar DP, Geiderman JM, et al. Emergency Department Crowding, Part 1- Concept, Causes, and Moral Consequences. Annals of Emergency Medicine. 53(5).
8. Singer AJ, Thode HC, Viccellio P, Pines JM. The Association Between Length of Emergency Department Boarding and Mortality. Academic Emergency Medicine. 2011; 18: 1324-1329.
9. Moskop JC, Sklar DP, Geiderman JM, et al. Emergency Department Crowding, Part 2- Barries to Reform and Strategies to Overcome Them. . Annals of Emergency Medicine. 53(5) 612-617.

Hippocratic Medicine No.1: Blood Culture or No Blood Culture, That is the Question.

Welcome to the first installment of our new column here at Everyday EBM - Hippocratic Medicine.  

Modeled after the Do No Harm project pioneered at the University of Colorado, the aim of this (hopefully) monthly installment will be on the avoidance of avoidable care i.e. raising awareness for how medical overuse has the potential to do patient harm.   Because every test or intervention we do has the potential for not just benefit but also harm, we should seek that our patients do better because of the care we provide instead of despite it.  

Clinical Scenario: It is a regular day in the emergency department and along with the regular smattering of chest pain rule-outs, vaginal bleeders, and abdominal pain, you have two patients who need to be admitted for IV antibiotics. One has a diffuse cellulitis of the left leg and the other pyelonephritis, unable to tolerate oral meds. Both have an elevated white count but no other SIRS criteria. When giving sign-out, the inpatient medicine team asks for blood cultures on both patients.  Is there any value for blood cultures in patients with cellulitis and pyelonephritis? Does this value outweigh the potential harms?

Literature Review:The ACEP article [1] “The evidence against blood cultures” presented interesting data regarding cost and benefit of blood cultures. According to the article, in 2010 $151 million dollars was spent on blood cultures. Only 4% to 7% of blood cultures were true positives. Alarmingly, blood cultures are almost as likely to give you a false positive as a true one: 40% of all "positive" cultures are false positives. For cellulitis, only 2% of patients are likely to develop a bacteremia and skin infections are almost always due to Staph or Strep. For uncomplicated pyelonephritis, the urine culture is what is used to target treatment, and if blood cultures are positive, it is almost always with the same organism and does not alter treatment course.

With regard to their recommendations for pyelonephritis, the ACEP article draws on a retrospective chart review of 212 patients admitted for uncomplicated pyelonephritis [2] . Blood cultures were performed for 105 of these patients, only 16% of which grew out an organism. Of the 11 positive cultures, all but 2 had the same organism that was identified in the urine and no change was made in treatment. The other 2 were found to have a second infectious source for their bacteremia.

With regard to cellulitis, a retrospective review of 710 patients admitted for cellulitis, of which 553 had blood cultures drawn. Of these patients, only 11 cultures (2%) were positive [3]. A 2012 review article in the Journal of infection found 7.9% of patients with cellulitis had positive cultures, all with Staph or Strep identified as the source organism [4]. 

These findings are not limited to the adult population [5].  A retrospective cohort study of blood culture results and microbiology laboratory charges for pediatric cases of community-acquired pneumonia and skin/soft tissue infection found that only 9/279 cultures (3.2%) grew an organism and only 5/9 (55%) were deemed to be true positives.  The main subsequent intervention?  Repeat cultures.  4/9 of these were deemed to be false-positives, leading to a smattering repeat cultures, ID consultation, prolonged LOS, and vancomycin initiation:

Table 2 from Parikh et. al. (Ref 5)
But are there clinical indicators that increase the diagnostic or therapeutic yield of blood cultures? The answer is yes. In a 1996 study, SIRS criteria was found to be 96% sensitive for positive blood cultures and this has been corroborated by other studies [6]. This indicates that in the absence of SIRS criteria aka in the absence of sepsis (2 SIRS + a known infectious source) blood cultures are more likely to be false positives than true positives, and do not meet standards for an indicated test.

As alluded to in the pediatric data, we may be doing more harm than good when ordering blood cultures in patients with uncomplicated [or shall we say SIRS(-) ?] pneumonia, cellulitis or UTI. Just like an incidental finding on an imaging study, false positive blood cultures have the power to beget further testing and intervention. Since we have learned above that the results are unlikely to change treatment course, we know that there are limited benefits. But what about the costs?

- Blood cultures increased cost and hospital length of stay
: A retrospective study from Ireland [7] compared "cases" of false-positive blood cultures [defined as a single blood culture set positive for micro-organisms commonly thought of as contaminants or multiple blood cultures positive for different organisms] with "controls" matched for comorbidity via the Charlson index with "true negative" blood cultures. They found an overall false positive rate of 4.7%, and that patients with false positive blood cultures stayed in the hospital for 5.4 days ( 95% CI 2.8 - 8.1 days) longer at a cost of $7502.20 more (95% CI: $4,925.80 - $10, 078.60) compared to counterparts matched for diagnosis and comorbidity. A similar study from Brigham and Women's Hospital published in 1991 [8] found essentially the same results (average increased LOS of 4.5 days and increased total cost of $4,385). 

Blood cultures increase unnecessary antibiotic use: In addition to adding to hospital length of stay, part of the additional costs incurred by false positive blood cultures are unnecessary antibiotics [8]. 
A prospective, blood culture cohort study [9] evaluated all blood culures positive for skin flora during a three month period at a US medical center.  In this study, they found 59 false positives aka contaminants with Coagulase Negative Staph in 3, 276 collections (compared with 20 cases of "true bacteremia" with the same organism).  Among the 59 patients in the false positive category, 24 (41%) were treated with antimicrobial agents, predominantly vancomycin.  It is unclear from reading the paper if this was a direct result of the positive blood culture, or due to continuation of empiric treatment; however, the results described by Alahmadi [7] and Bates [8] suggest that the culture results are at least in part responsible.  Beyond the aspect of monetary cost alone, there are a number of harms, including renal injury and spread of antibiotic resistance, that make unnecessary antibiotic use particularly troubling.

It has been written [8] that  "The true costs of a blood culture may greatly exceed the costs of the test itself".   How do we change this?  In the same way we make all clinical tests better - by using them in the appropriate situation and maximizing specificity.
                I. Decrease blood culture contamination rates:  The nationwide average for blood culture contamination is thought to be in the range of 3-5%.  At our own hospital (BJH), the blood culture contamination rate was within this range, with a rate of 3-4% for the emergency department compared with 1-2% for the ICU for 2014.  Several studies have demonstrated that increased nursing education and standardization of protocols can have significant impact on contamination rates. For example, one study for multiple centers in Sacramento saw a sustained drop from a 12% to 3% after instituting (and intensively educating about) a protocol of chlorhexidine-based skin cleaner and sterile glove technique in which a sterile glove is used for repalpating the site [10].
               II.  Use it in the appropriate clinical situation:  If you are admitting a patient with SIRS(-) pneumonia, UTI, or SSTI just don't do it.  However, make sure to send the urine culture before antibiotics (patient has not gone yet?  That's what a straight cath is for!). If the inpatient medicine team asks you to, use it as an opportunity for education.  Floridly septic?  Go ahead.  Think its endocarditis?  Sure.  

Submitted by Alicia Oberle, PGY-3 and Maia Dorsett (@maiadorsett), PGY-3

Reviewed by Ryan Schneider and Stephen Liang. 
Thank you to Maureen Keating and Carey-Ann Burnham of BJC Micro for our own contamination rate data.

1. Lin MP, Schurr JD. Arm Yourself for the “Cultural” Debate: The Evidence Against Blood Cultures. ACEP Now. Sept 2014 Vol 33 Number 9.
2. Pasternak EL, Topink MA. Blood Cultures in Pyelonephritis: do results change therapy? Acad Emerg Med. 2000; 7:1170.
3. Perl B, Gottehrer NP, Raveh D, et. al. Cost-effectiveness of blood cultures for adult patients with cellulitis. Clin Infect Dis. 1999; 29:1483-1488.
4. Gunderson CG, Martinello RA. A systematic review of bacteremias in cellulitis and erysipelas. Journal of Infection. 2012 Feb. 

5.Parikh, K., Davis, A. B., & Pavuluri, P. (2014). Do we need this blood culture?. Hospital pediatrics, 4(2), 78-84.
 6. Jones GR, Lowes JA. The systemic inflammatory response syndrome as a predictor of bacteremia and outcome from sepsis. QJM. 1996; 89:515-522. 7. Alahmadi, Y. M., Aldeyab, M. A., McElnay, J. C., Scott, M. G., Darwish Elhajji, F. W., Magee, F. A., ... & Kearney, M. P. (2011). Clinical and economic impact of contaminated blood cultures within the hospital setting. Journal of Hospital Infection, 77(3), 233-236.
8. Bates, D. W., Goldman, L., & Lee, T. H. (1991). Contaminant blood cultures and resource utilization: the true consequences of false-positive results. JAMA, 265(3), 365-369
9. Souvenir, D., Anderson, D. E., Palpant, S., Mroch, H., Askin, S., Anderson, J., ... & Campbell, D. M. (1998). Blood cultures positive for coagulase-negative staphylococci: antisepsis, pseudobacteremia, and therapy of patients. Journal of clinical microbiology, 36(7), 1923-1926.
10. Denno, J., & Gannon, M. (2013). Practical Steps to Lower Blood Culture Contamination Rates in the Emergency Department. Journal of Emergency Nursing, 39(5), 459-464.