Category Archives: In the Literature

Contrast-Induced Nephropathy: Confounding Causation

Author: Richard Sinert, DO (Professor of Emergency Medicine / Vice Chair of Research, SUNY Downstate Medical Center) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

I would like to applaud the study “Risk of Acute Kidney Injury After Intravenous Contrast Media Administration” by Hinson et al[1] in the February 2017 issue of Annals of Emergency Medicine.  Before discussing the details of this study, I would like to give a historical perspective on how the study of CIN has evolved.

Since the first observation by Bartels et al[2] of the association between between contrast administration and Acute Kidney Injury (AKI), multiple studies gave further added weight to the association between intravenous contrast and AKI[3-7].

Although CIN is defined by a relatively small change in serum creatinine (SCr) (25% from baseline or an absolute increase of 0.5 mg/dl 48-72 hours post infusion), the consequences for CIN patients at least on the surface seemed dire.  Among cardiac catheterization patients, CIN increased the mortality rates[3] from 6% to 16% in one study[7] and from 0.6% to 31% in another[6].  Higher composite mortality rates and need for renal replacement (relative risk = 36) were also observed in patients who met the definition for CIN following CT-PA, after intravenous contrast in pulmonary embolism patients who developed CIN[4].

At this point an iatrogenic injury (CIN) was linked to an easily measured disease marker (timed changes in SCr) that seemed to be associated with adverse outcomes.  Not surprisingly, the medical community with the best of intentions studied the risks[5],[6] and a wide-range[7],[8],[9] of potential measures to prevent CIN.

Yet all these studies documenting CIN incidence, risks, outcomes, and prophylactic strategies suffer a bias common to many observational studies— confounding bias[10],[11].   Confounding bias occurs when an exposure is inappropriately causally linked to an outcome, when a separate exposure (confounding variable) other than the one of interest better explains the observed outcome.  Since the definition of CIN requires a second timed measurement of SCr, these studies must select for a relatively ill group of hospitalized patients undergoing repeated laboratory testing; selection bias must be considered.  Decrements in kidney function signaled by a rise of SCr could have occurred from the incident disease before or after contrast administration.  In addition, intercurrent hemodynamic instability (eg., sepsis, hemorrhage, diuresis) and a multitude of nephrotoxins (eg., NSAID’s, ACE-Inhibitors, antibiotics) are common complications during hospitalization, which may also explain an increased SCr and associated higher mortality rates.  Newhouse et al[12] found that among 32,161 hospitalized patients not exposed to contrast, 19% of patients had a 25% increase in SCr, which would have fulfilled diagnostic criteria for CIN had they been exposed to IV contrast.

Lipsitch et al[13] stated that non-causal associations between outcomes and exposures are the result of either mismeasurement (recall bias), confounding bias, or selection bias.  To prevent confounding, Lipsitch et al[13] suggests designing a negative control experiment where the observation is repeated under conditions that are not expected to produce the outcome of interest.  If the outcome is encountered without the exposure, then a confounding bias may exist. This form of negative control experiment in which the incidence of AKI is compared across patients exposed and unexposed to contrast has been studied by multiple investigators[14], [15], [16], [17] , all failed to find a statistically significant difference in AKI rate (using CIN definition) between those exposed to contrast and controls.

These studies[18-21] that compared the incidence of CIN between contrast- exposed and unexposed groups also posed methodological issues related to the differences in the baseline risks of AKI between the two study groups.  It is not surprising that the patients hospitalized after requiring a contrast-enhanced CT may be inherently different that those not requiring a similar study.  To account for this potential selection bias, multiple studies have compared the incidence of AKI between contrast exposed and unexposed patients utilized propensity-scoring matching.  Propensity-score matching is a methodology that balances the baseline outcome risks between the study groups[18].  Even utilizing propensity-score matching for AKI, multiple studies[19], [20], [21], [22], [23] again failed to find a statistically higher incidence of AKI in the contrast- exposed compared to unexposed group of hospitalized patients.  In addition, the increases in risks of higher mortality rate in the CIN patients were not found when propensity-scoring matching accounted for the baseline risk of mortality of the contrast-exposed and non-contrast exposed patients.

The most recent CIN study by Hinson et al[1] in this recent issue of Annals of Emergency Medicine represents the latest in the line of investigations into the causal relationship between contrast and AKI.  Hinson et al[1] conducted a retrospective study over a 5-year period comparing the incidence of AKI among three groups, including contrast-enhanced CT (n=7,201), non-contrast enhanced CT (n=5,499), and those in whom CT was not performed (n=5,234).  These three groups were propensity-scoring matched for AKI risks.  AKI was defined both using the common CIN definition and definitions of AKI as reported in the Acute Kidney Injury Network/Kidney Disease Improving Global Outcomes (KDIGO) guidelines[24].   Applying the traditional definition of CIN, AKI was found in 10.6%, 10.2%, and 10.9% in contrast-enhanced CT, non-contrast CT, and non-CT groups, respectively.  Utilizing the KDIGO AKI definitions, AKI occurred in 6.7%, 8.9%, and 8.1% in contrast-enhanced CT, non-contrast CT, and non-CT groups, respectively.

Compared to previous propensity-scoring matched studies mentioned above, Hinson et al[1] went a step further by conducting a multiple logistic regression analysis, including in their model known predictors of AKI and contrast administration. From the multiple logistic regression model, contrast administration produced a non-significant odds-ratio for AKI as defined by both the CIN (0.96 [95% CI, 0.85-1.08]) and KDIGO criteria (1.00 [95% CI, 0.87-1.1.6]).  Moreover, the authors found no differences among the three study groups for the development of chronic kidney disease, need for dialysis, or renal transplantation in the following 6 months post-contrast exposure.

Although patients with elevated SCr (> 4.0 mg/dl) were excluded from their primary analysis, multiple logistic regression analysis of patients with elevated baseline SCr found no independent risk of AKI for contrast administration.

In conclusion, comparing the methodological rigor of more recent CIN studies to those in the past, it seems clear that earlier studies purporting a causal relationship between AKI and contrast administration were only identifying an association but not a true clinical entity. Older CIN studies were biased by confounding variables (e.g., hemodynamic instability, nephrotoxins), with well-established links to AKI providing a sufficient cause for AKI without implicating contrast as an additional AKI risk.

The history of the study of CIN is just another example of evidence-based medicine successfully applied to the debunking of a common belief in a clinical syndrome.  As ED physicians are faced with the challenge of rapidly diagnosing life-threatening conditions (i.e. aortic dissection/aneurysmal rupture, pulmonary embolism, occlusion or aneurysmal rupture of cerebral vessels, traumatic vascular injury), we should not delay emergent contrast-enhanced CT scans waiting for SCr.

 

References / Further Reading

[1] Hinson JS, Ehmann MR, Fine DM, et al. Risk of Acute Kidney Injury After Intravenous Contrast Media Administration. Ann Emerg Med 2017.

[2] Bartels ED, Brun GC, Gammeltoft A, Gjorup PA. Acute anuria following intravenous pyelography in a patient with myelomatosis. Acta Med Scand 1954;150:297-302.

[3] Pickering JW, Blunt IR, Than MP. Acute Kidney Injury and mortality prognosis in Acute Coronary Syndrome patients: A meta-analysis. Nephrology (Carlton, Vic) 2016.

[4] Mitchell AM, Jones AE, Tumlin JA, Kline JA. Prospective study of the incidence of contrast-induced nephropathy among patients evaluated for pulmonary embolism by contrast-enhanced computed tomography. Acad Emerg Med 2012;19:618-25.

[5] Mehran R, Aymong ED, Nikolsky E, et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol 2004;44:1393-9.

[6] Lin KY, Zheng WP, Bei WJ, et al. A novel risk score model for prediction of contrast-induced nephropathy after emergent percutaneous coronary intervention. International journal of cardiology 2017;230:402-12.

[7] Li H, Wang C, Liu C, Li R, Zou M, Cheng G. Efficacy of Short-Term Statin Treatment for the Prevention of Contrast-Induced Acute Kidney Injury in Patients Undergoing Coronary Angiography/Percutaneous Coronary Intervention: A Meta-Analysis of 21 Randomized Controlled Trials. American journal of cardiovascular drugs: drugs, devices, and other interventions 2016;16:201-19.

[8] Wang N, Qian P, Kumar S, Yan TD, Phan K. The effect of N-acetylcysteine on the incidence of contrast-induced kidney injury: A systematic review and trial sequential analysis. International journal of cardiology 2016;209:319-27.

[9] Subramaniam RM, Suarez-Cuervo C, Wilson RF, et al. Effectiveness of Prevention Strategies for Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis. Ann Intern Med 2016;164:406-16.

[10] Grimes DA, Schulz KF. Bias and causal associations in observational research. Lancet 2002;359:248-52.

[11] McNamee R. Confounding and confounders. Occup Environ Med 2003;60:227-34; quiz 164, 234.

[12] Newhouse JH, Kho D, Rao QA, Starren J. Frequency of serum creatinine changes in the absence of iodinated contrast material: implications for studies of contrast nephrotoxicity. AJR Am J Roentgenol 2008;191:376-82.

[13] Lipsitch M, Tchetgen Tchetgen E, Cohen T. Negative controls: a tool for detecting confounding and bias in observational studies. Epidemiology 2010;21:383-8.

[14] Cramer BC, Parfrey PS, Hutchinson TA, et al. Renal function following infusion of radiologic contrast material. A prospective controlled study. Arch Intern Med 1985;145:87-9

[15] Heller CA, Knapp J, Halliday J, O’Connell D, Heller RF. Failure to demonstrate contrast nephrotoxicity. Med J Aust 1991;155:329-32.

[16] Bruce RJ, Djamali A, Shinki K, Michel SJ, Fine JP, Pozniak MA. Background fluctuation of kidney function versus contrast-induced nephrotoxicity. AJR Am J Roentgenol 2009;192:711-8.

[17] Sinert R, Brandler E, Subramanian RA, Miller AC. Does the current definition of contrast-induced acute kidney injury reflect a true clinical entity? Acad Emerg Med 2012;19:1261-7.

[18] Haukoos JS, Lewis RJ. The Propensity Score. JAMA 2015;314:1637-8.

[19] Davenport MS, Khalatbari S, Dillman JR, Cohan RH, Caoili EM, Ellis JH. Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material. Radiology 2013;267:94-105.

[20] McDonald RJ, McDonald JS, Carter RE, et al. Intravenous contrast material exposure is not an independent risk factor for dialysis or mortality. Radiology 2014;273:714-25.

[21] Hsieh MS, Chiu CS, How CK, et al. Contrast Medium Exposure During Computed Tomography and Risk of Development of End-Stage Renal Disease in Patients With Chronic Kidney Disease: A Nationwide Population-Based, Propensity Score-Matched, Longitudinal Follow-Up Study. Medicine 2016;95:e3388.

[22] Tremblay LN, Tien H, Hamilton P, et al. Risk and benefit of intravenous contrast in trauma patients with an elevated serum creatinine. J Trauma 2005;59:1162-6; discussion 6-7.

[23] Cely CM, Schein RM, Quartin AA. Risk of contrast induced nephropathy in the critically ill: a prospective, case matched study. Critical care (London, England) 2012;16:R67.

[24] Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2:1-138.

GI Bleeds: Who Needs ICU Level Care?

Authors: Christina Thorngren, MD, MPH and Janna Welch, MD (University of Texas Dell School of Medicine Emergency Medicine Residency Program) // Edited by: Erica Simon, DO, MHA (@E_M_Simon), Brit Long, MD (@long_brit ), and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

It’s a busy Saturday night in the ED. Scanning the patient tracking board, you come across an ESI 2: A 55 year-old woman with a chief complaint of generalized weakness. The nursing note details a review of systems positive for epigastric abdominal pain and black stools of one week duration. VS: HR 110, BP 105/64. As the patient rolls by in a wheelchair, you note her impressive pallor. After offering a quick greeting, placing her on the monitor, and dropping orders, you make your way to the clerk’s desk to notify him of an anticipated admission. As the clerk makes inquires regarding the required bed, your focus shifts to the patient: is she stable enough for the ward or does she require ICU level care?

If you’ve had a similar inner monologue while treating a GI bleed, the discussion below offers a number of tools to aid in your clinical decision-making.

Introduction

Developing a clinical gestalt regarding a patient with a gastrointestinal bleed (GIB) can be challenging even for the seasoned emergency medicine physician. Anecdotally, we’ve all heard of the hemodynamically stable patient with one bloody bowel movement prior to arrival that acutely decompensates in the ED. While the decision to admit these patients to the ward versus the ICU may be clear in the setting of unstable VS or post endotracheal intubation, there are often times when we encounter shades of gray. The following discussion will hopefully shed some light on topic, and offer a quick discussion of risk stratification methods for EM physicians to utilize when addressing upper and lower GI bleeds.

Upper GIB

An upper GIB is defined as bleeding from a source proximal to the ligament of Treitz.1 Etiologies of upper GIBs include esophageal varices, peptic ulcers, gastritis, Mallory-Weiss tears, arteriovenous malformations, and rarely, Dieulafoy lesions (large diameter, tortuous vessels, protruding through the submucosa of the GI tract).2 Collectively, the annual incidence of upper GI bleeds is 48-180 cases per 100,000 adults, with a mortality ranging from 10-14%.1   Nearly 80% of upper GIBs resolve spontaneously, while 20% require acute intervention.1 Several studies have identified severe gastrointestinal bleeding (GI bleeding resulting in shock, or a decrease in hematocrit of ≥ 6% from baseline) as possessing a mortality rate of nearly 39%.1

While it is clear that patients with severe GI bleeds require inpatient admission, are there methods to determine when it is appropriate to discharge hemodynamically stable patients for outpatient follow-up?

Current literature cites the following scores for use in the mortality risk stratification of upper GIBs: the Clinical Rockall Risk Score,3 the Modified Glasgow-Blatchford Score,4,5 the AIMS65 Score,6 and the PNED Score.7,8 While these scores were initially developed to assess inpatient mortality in the setting of upper GIBs, secondary outcomes included risk for re-bleeds and 30 day mortality, making them useful tools for the emergency physician.3

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Is one of these methods superior to the others? Let’s quickly discuss the statistical method of comparison:

The utility of a scoring systems is determined by calculating the area under the receiver operating curve (AUROC). An AUROC of 1 is a perfect test that when employed, will accurately and precisely predict an outcome 100% of the time. In contrast, an AUROC of 0.5 is of little utility as it precisely and accurately predicts an outcome 50% of the time (i.e. – no better than flipping a coin).

Ideally, to assess the risk stratification methods detailed above, all scores would be applied to one cohort of patients, and the AUROC calculated and compared. To date, there have been no studies performed which directly compare the Clinical Rockall Risk Score, the Modified Glasgow-Blatchford Score, the AIMS65 Score, and the PNED Score. Of the research published:

  • In 2012, Cheng, et al.5 compared the Modified Glasgow-Blatchford Score and the Clinical Rockall Score as applied to 167 patients presenting with GIBs (study endpoint: in-hospital mortality or re-bleeding). An AUROCs of 0.85 (CI 0.72-0.98) for the Modified Glasgow-Blatchford Score, and 0.59 (CI 0.32-0.87) for the Clinical Rockall Risk Score (p <0.0022) was identified.
  • Marmo, et al.8performed a head-to-head comparison of the PNED score and Clinical Rockall Score in 1360 patients (end point: in-hospital mortality) and found respective AUROCs of 0.81 (CI 0.70-0.90) for PNED, and 0.66 (CI 0.6-0.72) for the Clinical Rockall Score (p-value of <0.000).
  • In 2016, Aubougergi et al.6 performed a comparison of the AIMS65 and the Modified Glasgow-Blatchford Score in 298 patients (endpoint: inpatient mortality), identifying an AUROC of 0.85 (CI 0.81-0.89) for AIMS65 and 0.66 (CI 0.61-0.72) for Modified Glasgow-Blatchford Score (p of <0.01).

While it is unclear which mortality stratification method is most appropriate for use by the emergency physician, it is safe to say that the higher the mortality risk as characterized by these scores, the greater the necessity for advanced levels of patient care.

Have any of these scores been directly assessed for utility in predicting the need for ICU admission?

Of the mortality risk stratification scores above, only the Clinical Rockall Score has been evaluated for its utility in determining the requirement for ICU-level care. In a study of 565 consecutive patients treated for acute upper GIBs at Wellington Hospital, New Zealand (1988-1991), Phang et al.7 identified an overall mortality rate of 22% in patients presenting with a Clinical Rockall score of 4-7, leading the authors to identify this as a high-risk population requiring ICU level care.7

Publications to watch:

Of note, an abstract by Raemakers et al. was recently published online (prior to the full article in Academic Emergency Medicine), discussing the value of pre-endoscopic risk scores for upper GIBs in the ED. For more information as it becomes available:

Ramaekers R, Mukarram M, Smith C, Thiruganasambandamoorthy V. The predictive value of pre-endoscopic risk scores to predict adverse outcomes in emergency department patients with upper gastrointestinal bleeding — A systematic review. Acad Emerg Med 2016 Sep 19; [e-pub]. (http://dx.doi.org/10.1111/acem.13101)

 Lower GI Bleeding

The majority of life-threatening bleeds originate from the upper GI tract, however profuse bleeding from the lower GI tract often causes hemodynamic instability. Approximately 20-25% of GIBs are distal to the ligament of Treitz, and result in a mortality rate of 2%- 4% (mortality has been demonstrated to increase with advancing age).9 Potential sources of lower GIBs include diverticular disease, malignancy, angiodysplasia, and colitis.9

Unlike upper GIBs, there is far less consensus regarding risk stratification parameters for lower GIBs. Several studies have demonstrated low systolic blood pressure, tachycardia, the use of aspirin, and the presence of medical comorbidities as increasing the risk of mortality in the setting of a lower GIB.9-11

In their study of 688 patients presenting with lower GIBs, Chong, et al.10 demonstrated a lack of reported abdominal tenderness as an independent risk factor for mortality (possibly as pain is often associated with more benign etiologies of bleeding, and could lead to earlier patient evaluation and treatment).10 The authors also identified prolonged bleeding (> 4 hours) as a risk factor for mortality in the setting of lower GIB.10,11

In conducting their study, Chong et al. also utilized a cohort of 410 patients to develop a clinical prediction score (HAKA score) to identify patients most likely presenting with a severe lower GIB. The authors identified severe bleeding as: bleeding requiring transfusion of ≥ 2 units of packed red blood cells, manifesting as a decrease in hematocrit of > 20% from baseline, recurrent bleeding within 24 hours, or readmission for lower GI bleeding within one week of initial presentation. The HAKA score, detailed below, demonstrated a PPV (for scores ≥ 2) of 44% for severe lower GI bleed, and a NPV of 88%.10

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Recognizing the need to investigate risk factors for severe lower GIBs, in 2003 Strate and colleagues published data characterizing presenting symptoms of lower GIBs and their odds of association with severe bleeding (as defined above by Chong, et al.).11 In 252 consecutive patients presenting to Brigham and Womens’ hospitals in Boston, MA from 1996-1999, the following characteristics were associated with severe lower GI bleeding:

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Conclusion

Extensive research has been performed in an attempt to develop clinical decision-making tools for the risk stratification of patients with GI bleeds. Ultimately, patients who are hemodynamically unstable, risk stratify as having a high mortality secondary to GI bleeding, or are at risk for having a severe lower GI bleed, should be admitted to an ICU setting.

Back to the Case

Review of the patient’s electronic health record reveals a history of chronic back pain (prescribed naproxen), hypertension, and hyperlipidemia. Initial screening labs identify a Hgb of 8.1 and BUN of 45. The patient is likely experiencing an upper GIB secondary to NSAID therapy. Utilizing the Modified Glasgow-Blatchford Scale, you quickly identify the patient as having a high risk of mortality. After consulting for ICU admission, you contact gastroenterology. The next morning you open the patient’s record and note the identification of a NSAID gastropathy on endoscopy. The patient ultimately required a blood transfusion, but is hemodynamically stable.

References / Further Reading

  1. Barkun A, Bardou M, Kuipers E, Sung J, Hunt R et al. International concensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010; 152:101-113.
  2. Baxter M and Aly E. Dieulafoy’s lesion: Current trends in diagnosis and management. Ann R Coll Surg Engl. 2010; 92(7): 548-554.
  3. Monteiro S, Goncalves T, Magalhaes J, Cotter J. Upper gastrointestinal bleeding risk scores: Who, when and why? World J Gastrointest Pathophysiol. 2016; 7(1):86-96.
  4. Blatchford O, Murray W, Blatchford M. A risk score to predict need for treatment for upper-gastrointestinal haemorrhage. Lancet. 2000; 356(9238):1318-1321.
  5. Cheng D, Lu Y, Sekhon H, Wu B. A modified glasgow blatchford score improves risk stratification in upper gastrointestinal bleed: a prospective comparison of scoring systems. Alimen Phamacol Ther. 2012; 36(8): 782-789.
  6. Abougergi M, Charpentier J, Berthea E, Rupawala A, Dheder J, et al. A prospective, multicenter study of the aims65 score compared with the Glasgow-blatchford score in predicting upper gastrointestinal hemorrhage outcomes. J Clin Gastroenterol. 2016; 50(6): 464-469.
  7. Phang T, Vornik V, Stubbs R. Risk assessment in upper gastrointestinal haemorrhage: implications for resource utilization. N Z Med J. 2000; 113(1115):331-333.
  8. Marmo R, Koch M, Cipolletta L, Capurso L, Grossi E, et al. Predicting moratlity in non-variceal upper gastrointestinal bleeders: validation of the Italian pned score and prospective comparison with the rockall score. Am J Gastroenterol. 2010;105(6):1284-1291.
  9. Qayed E, Dagar G, Nanchal R. Lower gastrointestinal hemorrhage. Crit Care Clin. 2016: 32(2):241-254.
  10. Chong V, Hill A, MacCormick A. Accurate triage of lower gastrointestinal bleed (LGIB) – a cohort study. Int J Surg. 2016; 25:19-23.
  11. Strate L, Orave E, Syngal S. Early predictors of severity in acute lower intestinal tract bleeding. Arch Intern Med. 2003;163(7):838-843.

Controversies in Pulmonary Embolism Imaging and Treatment of Subsegmental Thromboembolic Disease

Author: Brit Long, MD (@long_brit, EM physician at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

Pulmonary embolism (PE) is classically a life-threatening diagnosis, often considered in the work-up of patients with chest pain or dyspnea.  Initial mortality rates of missed, untreated PE has been quoted as high as 26%, based on a 1960 study.1  This disease is common, with 400,000 patients affected with nonfatal PE and another 200,000 patients in the U.S. dying each year from this disease. PE is the third most common cause of death in cardiovascular disease after myocardial infarction and stroke.2,3

With this risk of mortality, physicians through the years have been tasked with diagnosing and managing PE.  Unfortunately, no individual risk factor, symptom, or clinical sign can definitively diagnose or exclude PE.4,5  Thus, evaluation for PE often includes clinical decision rules, laboratory tests, and several imaging modalities. These tools have been developed to provide physicians with avenues for the evaluation and diagnosis of PE. However, the availability of these tests has resulted in increased test use and number of PE diagnoses. In particular, the use of D-dimer and computed tomography pulmonary angiography (CTPA) has remarkably increased. However, mortality from PE has not changed with increased rates of diagnosis. With the increased testing for PE and sensitivity of CTPA, the diagnosis of subsegmental PE and incidental PE is increasing.5-7 Controversy currently exists in the use of CTPA for PE and treatment of these lesions.7 Recent literature and guidelines have sought to answer these questions, illuminating the path for proper diagnosis, evaluation, and management.7-11

Diagnosis and Testing

The primary diagnostic utility until the late 1990s was ventilation-perfusion (VQ) scanning. However, CT angiography became widely popular after the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) studies, which demonstrated the ease of use, convenience, and adequate sensitivity of CTPA in the evaluation for PE.12,13 The test could reliably diagnose central PE, but the modality was limited in imaging peripheral pulmonary vasculature.13,14 With the advent of multidetector row CTPA, imaging the subsegmental vasculature became feasible.8,9,13-15

CTPA is the test of choice for the majority of physicians in the evaluation for PE. A survey of emergency physicians found a strong preference for CT in PE evaluation, especially as a first line test for the disease.8,9,15-18 Unfortunately, many physicians order imaging without risk stratification first through utilization of clinical gestalt, Wells criteria, or revised Geneva score (RGS).9,16 Studies have demonstrated the benefit of risk stratification in association with the pulmonary embolism rule-out criteria (PERC). In low risk patients with negative PERC, no further testing is required. If the patient is PERC positive or intermediate risk, then testing with D-dimer is warranted. However, even D-dimer testing in patients with low to intermediate risk is often not completed in preference for imaging.8,9,11 Literature has demonstrated that providers do not adhere to PIOPED II recommendations concerning PE imaging. In one study, CTPA was completed in 45.5% of patients meeting imaging recommendation, defined by revised Geneva score pulmonary embolism likely or if PE unlikely with positive D-dimer.19 In the majority of emergency departments, CTPA is the default test, as it is available at all hours and affords higher diagnostic capability for other diseases that can present with chest pain or dyspnea.8,9

An increase in CT use is immediately apparent upon review of recent years. From 1998 to 2006, the detection of PE rose by approximately 80% (62.1 to 112.3 per 100,000 US adults).8,9,16 However, no change in US mortality from PE was found in the same time period.16,21 As scanning technology has advanced with improved resolution, this test is able to detect smaller clots, particularly small filling defects in subsegmental arteries 2-3 mm in diameter.22  These scanners can now cover the entire thorax in one breath-hold, and imaging of peripheral pulmonary arteries down to fifth order branches is possible.22-24  High quality CTPAs require contrast opacification of 200 Hounsfield units in the pulmonary artery. Normal scanning technique requires the patient to hold his or her breath for several seconds. During the scan, injection of 120 ml of intravenous contrast is completed, which requires a 20 gauge or larger intravenous line.25,26  Four detector CTPA technology demonstrated initial diagnosis rates of 5% for isolated subsegmental pulmonary embolism (SSPE).6 Updated imaging technology with 64-detector CTPA have resulted in rates as high as 12% for SSPE.27

The Dangers of Increased Testing

No improvement in patient outcomes has occurred with increased testing for PE in the inpatient, outpatient, and emergency settings. These tests may be associated with actual patient harm, and more than one third of patients will undergo a second CTPA within 5 years of the first scan.28  Radiation from CT scanning has been associated with higher incidence of malignancy in several populations.29,30  One scan imparts 10-20 mSv of radiation, creating a lifetime risk of fatal cancer of 1 in 500 per CT. In particular, women are at greatest risk due to the presence of radiosensitive breast and thoracic tissue.31-33 In addition to increased radiation, other complications include anaphylaxis and anaphylactoid reactions to contrast. Prior allergy to iodinated contrast is associated with a 6-15% risk of recurrence with second exposure, as compared to 1% risk in patients with no prior reactions.34 Extravasation of contrast into a limb occurs in less than 1 per 500 patients, but this can lead to severe pain and compartment syndrome.35

The intravenous contrast utilized is associated with nephropathy, with greater risk in patients of older age and co-morbidities such as renal disease.35-37  One study demonstrated nephropathy due to contrast in 14% of patients undergoing CTPA for PE evaluation.37 Contrast nephropathy is defined by a rise of serum creatinine by 25% from baseline value, which has been associated with worse outcomes.36-38

Overdiagnosis and treatment can also increase healthcare costs, as the average charge for PE admission increased by $19,000 from 1998 to 2006.39 Warfarin anticoagulation with testing and clinic visits approached $2,700 in 2006, while the new oral anticoagulants approached $3,000 per year.40,41  A 2015 study found the cost of medical care to be lower for low-risk patients with VTE immediately discharged from the ED with rivaroxaban therapy compared with patients receiving heparin and warfarin. Costs at 6 months for the heparin-warfarin group were over $11,000, while those for the new oral anticoagulant approximated $4,800.42

The Quandary: Incidental and Subsegmental PE

Incidental PE

Numerous studies have demonstrated the increased prevalence of incidental emboli with rates varying from 0.5% to 5%, depending largely on the scanning technology, the reviewer of the test, and the population under study (cancer versus non-cancer, as well as inpatient versus outpatient).43-49  One study evaluated incidental PE found in consecutive inpatients imaged with MDCT (the majority 16-slice scanners). Nine out of 28 scans were found to be positive by a thoracic radiologist which were initially read negative by the first reporting radiologist. All of these thrombi were located in segmental or subsegmental vasculature. Unsuspected emboli were found in 5.7% of scans.50 Other studies have found comparable numbers with 64 slice scanners, with a prevalence of unsuspected PE of 4.3% in an inpatient population. Interestingly, these unsuspected PE were present in almost 17% of those over 80 years, with none found in those below 50 years.47,48

These two studies found a strong correlation with malignant disease and incidental PE as well, with rates of 70% in the Gosselin et al. and 83% in the Storto et al. studies.47,48  However, these patients often receive more CT imaging due to the need for disease staging. Tertiary cancer centers have reported similar numbers as these other two studies, with rates of 4% in asymptomatic patients.50 Interestingly, Ritchie found no significant difference in incidental PE prevalence in patients with history of malignancy and patients without cancer.51 However, with these numbers, two points require discussion. First, though these studies have a high prevalence of patients with malignancy and incidental pulmonary embolism, it does not necessarily mean that patients with malignancy are predisposed to PE. Other risk factors require consideration. Second, the finding of incidental PE in a patient with no malignancy should not trigger a hunt for malignancy.53

 Subsegmental PE

Subsegmental lesions also present a quandary, as the opacity could represent a true PE or artifact with no disease. Numerous studies demonstrate this difficulty. The positive predictive value of CTPA for SSPE may be only 25%, with low inter-observer agreement between radiologists (K 0.38, 95 % CI 0.0–0.89).12,52 A prior study found 11% of SSPE diagnoses were false positive upon a second read by thoracic radiologists.54 One study in Ireland evaluated 937 CTPAs, with PE the initial diagnosis in 174 (18.6% of scans). Investigators found a 25.9% false positive rate, with 59.4% of subsegmental PE read as false positive.55 Studies of PE diagnosis using five different radiologists found that for subsegmental PE, one reviewer dissented with the initial reviewer’s interpretation in 60% of cases. False positive rates were 15% for subsegmental PE and 3.6% for segmental PE.56,57

Suboptimal images are obtained in approximately 10% of formal CTPA interpretations.8,9,12,58 Several reasons exist for this, producing increased false positive rates and decreased specificity. Obesity increases risk of inadequate imaging due to greater amounts of soft tissue. As the pulmonary vasculature tapers, the contrast capture and opacification quality decrease. This increases the risk of artifact, either beam-hardening or with motion due to patient respiration.  Increases in false positive rates occur with more peripheral location of lesions, decreased size of the lesion (defined by the short-axis diameter), and decreasing quality of the CT study.9,57

Are Incidental and Subsegmental PEs Harmful?

Controversy exists whether these emboli, including incidental and subsegmental PE specifically, are associated with harm if left untreated. Some argue that small clots do not require treatment, as the lungs function as a sieve to prevent these clots from traveling to the arterial circulation, potentially causing issues such as stroke. Emboli in the lungs are thought to be resorbed by the body without clinical effect.59,60

Postmortem studies have demonstrated a rate of incidental PE ranging from 9% to 63%, with the authors suggesting these emboli were likely not related to the cause of death.60-64 Patients with missed PE who are not anticoagulated may not have an adverse outcome.65 In 25 untreated patients with subsegmental PE, no deaths attributable to PE were found.66  One study suggested that for patients with unacceptable risks of anticoagulation, treatment for incidental PE may be held if adequate pulmonary reserve is present and no lower extremity deep venous thrombus (DVT) is discovered.59 A 2010 study evaluating patients with subsegmental PE found a SSPE rate of 4.7%. Three month VTE risks in patients receiving no treatment were 0.9% (95% CI: 0.4-1.4) and 1.1% (95% CI: 0.7-1.4) for patients who underwent single and multidetector CTPA, respectively.6 These studies support the low risk of adverse outcome and recurrent VTE in patients with isolated SSPE with adequate pulmonary reserves and no DVT.

However, a study by den Exter et al. challenged the notion subsegmental PE is not harmful.66 The authors found that among 116 patients with subsegmental PE and 632 patients with proximal PE, recurrent VTE rates did not differ between the two groups at 3 months, with 3.6% of the SSPE and 2.4% of the proximal PE groups experiencing recurrent VTE. The risk of all-cause mortality was 10.3% for SSPE, 6.3% for proximal PE, and 5.4% for patients without PE. These rates were not statistically significant, though the investigators stated patients with SSPE to be at increased risk for VTE at follow up with a hazard ratio 3.8 (95% CI: 1.3-11.1). The authors of this study conclude that SSPE has similar clinical course and outcomes to that of proximal PE, specifically mortality and recurrent VTE.66 These results should be considered carefully, as the patients in the SSPE group experienced greater mortality when compared to patients with proximal PE. An important aspect of this study is the prevalence of comorbidities present in the SSPE and proximal PE patients, including higher rates of malignancy than the standard population. Many of the patients included had concomitant DVT as well, and most providers would agree DVT in the setting of SSPE requires treatment.

A Cochrane review released in 2016 evaluating the literature up to December 2015 found no studies that met inclusion criteria. The investigators state there is no randomized control trial evidence for anticoagulation versus no treatment in patients with SSPE or incidental PE. No conclusions were provided.67

Treatment

The standard of care in the initial management of VTE has been heparin since the late 1950s.1 Until recently, all patients with PE have been anticoagulated in a similar manner, no matter the location, number, and size of the thrombus, and the majority of patients were admitted for treatment. However, recent literature has now supported outpatient treatment for patients low risk utilizing risk stratification and shared decision making.   New oral anticoagulants are gaining popularity for anticoagulation, and patients at low-risk for adverse outcome may be safe for discharge with these anticoagulant agents.68-70 Little argument exists for treating segmental PE.8,9 However, the dilemma occurs when considering management of the patient with subsegmental PE.

Some guidelines recommend anticoagulation for all emboli found, but others acknowledge that anticoagulation may not be warranted in all cases due to the uncertainty in treating isolated subsegmental PE.71,72  Many patients with SSPE may be treated without benefit, as well as increased risk.73 Donato in 2010 found patients with SSPE not anticoagulated experienced a recurrence and mortality rate of 0% at 3 month follow up.74 Experts in thromboembolism have recommended not anticoagulating patients with subsegmental PE with adequate pulmonary reserve.75

In the setting of subsegmental PE, providers must balance the risks and benefits of treatment, namely increased bleeding risk versus reduced recurrent VTE. In some studies, these bleeding complications are more common than recurrent thromboembolism, which is the condition treatment is meant to prevent. 74-76  In one case series of patients with subsegmental PE anticoagulated, risk of major bleeding was 5.3%, compared to recurrent thromboembolism at 0.7%.74 Another study found increased complications from anticoagulation in patients admitted to hospital from PE increased to 5.3% from 3.1 % in an 8 year period.21

The American College of Chest Physicians (ACCP) has recently updated treatment guidelines, published in 2016, providing recommendations on treatment of SSPE:10

-In patients with subsegmental PE (no proximal pulmonary artery involvement), no proximal DVT, and low risk for recurrent VTE, clinical surveillance over anticoagulation is recommended (Grade 2C).

-If high risk for recurrent VTE, anticoagulation is recommended (Grade 2C).* In this setting, ultrasound of the lower extremities should be obtained to exclude proximal DVT.

*The following are at risk for recurrent VTE: patients who are hospitalized or have reduced mobility for another reason; have active cancer (metastatic or being treated with chemotherapy); or have no reversible risk factor for VTE such as recent surgery. A low cardiopulmonary reserve or marked symptoms that cannot be attributed to another condition favor anticoagulant therapy, whereas a high risk of bleeding favors no anticoagulant therapy.

The ACCP cites two reasons for uncertainty in anticoagulation SSPE. First, the abnormality is small and may be a false-positive, rather than a segmental PE. Second, if a true subsegmental PE resulted from a small DVT, these are likely to have small risk of progression or recurrent VTE.10

A diagnosis of true subsegmental PE is more likely a true positive in the setting of high quality CTPA with good contrast opacification of distal pulmonary vasculature, multiple intraluminal defects are present, the defects also include proximal vessels, defects are present on multiple slices/images, contrast surrounds the defects (rather than the defect adhering to the vascular wall), patients are experiencing symptoms, a high-pretest probability is present for PE, and the D-dimer level is elevated.4,5,8-10,75

Treatment is recommended if the patient has multiple SSPE, symptoms are present, or if a DVT is also present. On the other hand, if the SSPE is a single lesion, a DVT is not present, and the patient has no symptoms related to PE, treatment may be deferred. 4,5,8-10,75

What can the provider do?

How can providers improve the current state of PE diagnosis and management?11 The first, and most important step, involves engaging the patient in a shared decision making model for the diagnostic process. This may reduce testing, which has been demonstrated in patients with chest pain.77

The second aspect of PE management involves understanding that PEs will be missed. Unfortunately, emergency physicians cannot diagnose every PE. However, in the appropriate patient who is low risk for adverse outcome, this may not harm the patient, but increased testing and over treatment is associated with risk. Over testing can potentially harm the patient through increased radiation and anticoagulation.

When evaluating the patient with concern for PE, patient risk stratification is essential utilizing Wells criteria, RGS, or clinical gestalt. Approximately two thirds of patients require no testing with adequate risk stratification.8,9  A combination of low risk and low pretest probability in association with negative PERC rule produces a probability of PE of less than 2% (approximately 0.3%), where the risk of further testing outweighs the risk of failure to diagnose PE. 78-81  The PERC rule has demonstrated sensitivities of 97% in a meta-analysis of 14,844 patients.78 However, the PERC rule should not be applied to intermediate or high risk patients.8,9

If the patient is intermediate risk or PERC positive, obtain quantitative D-dimer. The D-dimer possesses a serum half-life of 8 hours and is abnormally elevated for 3 days following symptomatic thrombus.82-85 Ensure the D-dimer is age-adjusted for patients over age 50 years. A threshold of age X 10 ng/mL results in sensitivities greater than 97% in all patients, no matter with ages over 50 years, while also increasing the specificity of the test.86,87

With high-risk patients, imaging with CTPA is recommended for evaluation. If concern for radiation, contrast nephropathy, or contrast reaction is present, consider the use of bilateral DVT study and/or ventilation-perfusion scan.8,9

If a SSPE is discovered, several components should be evaluated: the patient, the scan, and other tests.10 This can be completed through the consideration of the following: 1) Evaluate the patient for risk factors (immobility, hospitalization, comorbidities) and symptoms. 2) Speak with the radiologist about the study obtained, and question whether artifacts could be present. 3) Consider other imaging tests such as bilateral DVT studies.  If CTPA demonstrates SSPE, obtain DVT studies to evaluate for other thrombi. Presence of DVT is a marker for recurrent VTE and predictor of mortality for patients with PE.4,5,75

In the setting of SSPE, treatment is likely warranted for patients with symptoms or risk factors, multiple SSPE on high quality scan, or a DVT with SSPE. On the other hand, if the patient has adequate cardiopulmonary reserve, no DVT is found on other imaging modalities, and persistent risk factors are not present, further treatment may be held until follow up.4,5,7,10

Summary

CTPA is the first-line imaging modality for PE and has developed the ability to image pulmonary vasculature down to fifth order branches. However, this test is not without risk including radiation, contrast reaction, and contrast nephropathy. With the ever-increasing imaging capability of CTPA, the diagnosis of incidental and subsegmental PE is increasing, Controversy has occurred concerning the potential dangers of these lesions and whether treatment is warranted. The literature differs in demonstrating harm of SSPE. Fortunately, the ACCP recently released updated guidelines for the treatment of SSPE taking into account the patient, the scan, and other imaging modalities.  Ultimately, providers must reign in testing and use risk stratification, in association with shared decision making, in the evaluation and treatment of PE.

References/Further Reading

 

  1. Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. Lancet 1960;1(7138):1309–12.
  2. Cushman M, Tsai AW, White RH, Heckbert SR, Rosamond WD, Enright P, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med 2004 Jul;117(1):19-25.
  3. Heit JA. The epidemiology of venous thromboembolism in the community: implications for prevention and management. J Thromb Haemost 2006 Feb;21(1):23-29.
  4. Chunilal SD, Eikelboom JW, Attia J, Miniati M, Panju AA, Simel DL, et al. Does this patient have pulmonary embolism? JAMA 2003;290:2849-58.
  5.  Carrier M, Righini M, Le GG (2012) Symptomatic subsegmental pulmonary embolism: what is the next step? J Thromb Haemost 10:1486–1490
  6.  Carrier M, Righini M, Wells PS, Perrier A, Anderson DR, Rodger MA, Pleasance S, Le GG. 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;8:1716–1722.
  7. Raskob GE. Importance of subsegmental pulmonary embolism. Blood 2015; 122(7):1095-1096.
  8. Raja AS, Greenberg JO, Qaseem A, Denberg TD, Fitterman N, Schuur JD, et al. Evaluation of Patients With Suspected Acute Pulmonary Embolism: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med 2015;163:701-711.
  9. Kline JA and Kabrhel C. Emergency Evaluation for Pulmonary Embolism, Part 2: Diagnostic Approach. JEM 2015;49(1):104-117.
  10. Kearon C, Akl EA, Ornelas J, Blaivas A, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline. Chest 2016. DOI: 10.1016/j.chest.2015.11.026
  11. Green SM, Yealy DM. Right-sizing testing for pulmonary embolism: recognizing the risks of detecting any clot. Ann Emerg Med 2012; 59:524-526.
  12. Stein PD, Fowler SE, Goodman LR, et al, for the PIOPED II Investigators. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med 2006;354:2317-2327.
  13. Mullins MD, Becker DM, Hagspiel KD, Philbrick JT. The role of spiral volumetric computed tomography in the diagnosis of pulmonary embolism. Arch Intern Med 2000;160(3):293-8.
  14. Rathbun SW, Raskob GE, Whitsett TL. Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review. Annals of Internal Medicine 2000;132(3):227–32.
  15. Le Gal G, Righini M, Parent F, van Strijen M, Couturaud F. Diagnosis and management of sub-segmental pulmonary embolism. Journal of Thrombosis and Haemostasis 2006;4 (4):724-31.
  16. Wiener RS, Schwartz LM, Woloshin S. When a test is too good: how CT pulmonary angiograms find pulmonary emboli that do not need to be found. The BMJ 2013;347:f3368
    1. Weiss CR, Scatarige JC, Diette GB, Haponik EF, Merriman B, Fishman EK. CT pulmonary angiography is the first-line imaging test for acute pulmonary embolism: a survey of US clinicians. Acad Radiol 2006;13:434-46.
    2. Smith-Bindman R, Miglioretti DL, Johnson E, Lee C, Feigelson HS, Flynn M, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA 2012;307:2400-9.
    3. Adams DM, Stevens SM, Woller SC, Evans RS, Lloyd JF, Snow GL, Allen TL, Bledsoe JR, Brown LM, Blagev DP, Lovelace TD, Shill TL, Conner KE, Aston VT, Elliott CG. Adherence to PIOPED II investigators’ recommendations for computed tomography pulmonary angiography. Am J Med 2013 Jan;126(1):36-42.
    1. Ikesaka R and Carrier M. Clinical significance and management of subsegmental pulmonary embolism. J Thromb Thrombolysis 2015;39:311–314.
    2. Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med 2011;171:831-7.
    3. Ghaye B. Peripheral pulmonary embolism on multidetector CT pulmonary angiography. JBR-BTR 2007;90:100-8.
    4. Ghaye B, Szapiro D, Mastora I, et al. Peripheral pulmonary arteries: how far in the lung does multi- detector row spiral CT allow analysis? Radiology 2001;219:629–36.
    5. Raptopoulos V, Boiselle PM. Multi-detector row spiral CT pulmonary angiography: comparison with single-detector row spiral CT. Radiology 2001;221:606–13.
    6. Burnside P, Kline JA. Indirect computed tomography venography: quality of vascular opacification and diagnostic implications. Emerg Radiol 2010;17:195–202.
    7. Mos IC, Klok FA, Kroft LJ, et al. Safety of ruling out acute pulmonary embolism by normal computed tomography pulmonary angiography in patients with an indication for computed tomography: systematic review and meta-analysis. J Thromb Haemost 2009;7: 1491–8.
    8. Pesavento R, de Conti G, Minotto I, Filippi L, Mongiat M, de Faveri D, Maurizi F, Dalla VF, Piovella C, Pagnan A, Prandoni P (2011) The value of 64-detector row computed tomography for the exclusion of pulmonary embolism. Thromb Haemost 105:901–907.
    9. Kline JA, Courtney DM, Beam DM, et al. Incidence and predictors of repeated computed tomographic pulmonary angiography in emergency department patients. Ann Emerg Med 2009;54:41–8.
    10. Amis ES Jr,Butler PF,Applegate KE, Birnbaum SB, Brateman LF, Hevezi JM, et al, American College of Radiology. American College of Radiology white paper on radiation dose in medicine. J Am Coll Radiol. 2007;4:272-84.
    11. Brenner DJ, Hall EJ. Computed tomography—an increasing source of radiation exposure. N Engl J Med. 2007;357:2277-84.
    1. Einstein AJ, Henzlova MJ, Rajagopalan S. Estimating risk of cancer associated with radiation exposure from 64-slice computed tomography coronary angiography. JAMA 2007;298:317–23.
    2. Health Physics Society. Radiation exposure from medical diag- nostic imaging procedures Health Physics Society fact sheet. McLean, VA: Health Physics Society; 2008.
    3. Parker MS, Hui FK, Camacho MA, et al. Female breast radiation exposure during CT pulmonary angiography. AJR Am J Roentgenol 2005;185:1228–33.
    4. Kopp AF, Mortele KJ, Cho YD, et al. Prevalence of acute reactions to iopromide: postmarketing surveillance study of 74,717 patients. Acta Radiol 2008;49:902–11.
    5. Mitchell AM, Jones AE, Tumlin JA, et al. Immediate complications of intravenous contrast for computed tomography imaging 
in the outpatient setting are rare. Acad Emerg Med 2011;18:1005–9.
    6. Mitchell AM,Jones AE,Tumlin JA, Kline JA. Incidence of contrast-induced nephropathy after contrast-enhanced computed tomography in the outpatient setting. Clin J Am Soc Nephrol. 2010;5:4-9.
    7. Mitchell AM, Jones AE, Tumlin JA, Kline JA. Prospective study of the incidence of contrast-induced nephropathy among patients evaluated for pulmonary embolism by contrast-enhanced computed tomography. Acad Emerg Med 2012;19:618-25

     

    1. Sinert R, Brandler E, Subramanian RA, et al. Does the current definition of contrast-induced acute kidney injury reflect a true clinical entity? Acad Emerg Med 2012;19:1261–7.
    2. Park B, Messina L, Dargon P, Huang W, Ciocca R, Anderson FA. Recent trends in clinical outcomes and resource utilization for pulmonary embolism in the United States: findings from the nationwide inpatient sample. Chest 2009;136:983-90.
    3. Bullano MF, Willey V, Hauch O, Wygant G, Spyropoulos AC, Hoffman L. Longitudinal evaluation of health plan cost per venous thromboembolism or bleed event in patients with a prior venous thromboembolism event during hospitalization. J Manag Care Pharm 2005;11:663-73.
    4. Gage BF. Cost of dabigatran for atrial fibrillation. BMJ 2011;343:d6980.
    5. Kahler ZP, Beam DM, Kline JA, Hiestand B. Cost of Treating Venous Thromboembolism With Heparin and Warfarin Versus Home Treatment With Rivaroxaban. Acad Emerg Med 2015;22(7):796-802.
    6. Sebastian AJ, Paddon AJ. Clinically unsuspected pulmonary embolism: an important secondary finding in oncology CT. Clin Radiol 2006;61:81–5.
    7. Verschakelen JA, Vanwijck E, Bogaert J, et al. Detection of unsuspected central pulmonary embolism with conventional contrast-enhanced CT. Radiology 1993;188:847–50.
    8. Patel JJ, Chandrasekaran K, Maniet AR, et al. Impact of incidental diagnosis of clinically unsuspected central pulmonary artery thromboembolism in treatment of critically ill patients. Chest 1994;105:986–90.
    9. Winston CB, Wechsler RJ, Salazar AM, et al. Incidental pulmonary emboli detected at helical CT: effect on patient care. Radiology 1996;201:23–7.
    10. Gosselin MV, Rubin GD, Leung AN, et al. Unsuspected pulmonary embolism: prospective detection on routine helical CT scans. Radiology 1998;208:209–15.
    11. Storto ML, Di Credico A, Guido F, et al. Incidental detection of pulmonary emboli on routine MDCT of the chest. AJR Am J Roentgenol 2005;184:264–7.
    12. Engelke C, Manstein P, Rummeny EJ, et al. Suspected and incidental pulmonary embolism on multidetector-row CT: analysis of technical and morphological factors influencing the diagnosis in a cross-sectional cancer centre patient cohort. Clin Radiol 2006;61:71–80.
    13. Gladish GW, Choe DH, Marom EM, et al. Incidental pulmonary emboli in oncology patients: prevalence, CT evaluation, and natural history. Radiology 2006;240:246–55.
    14. Ritchie G, McGurk S, McCreath C, et al. Prospective evaluation of unsuspected pulmonary embolism on contrast enhanced CT (MDCT) scanning. Thorax 2007;62:536–40.
    15. Ghanima W, Nielssen BE, Holmen LO, Witwit A, Al-Ashtari A, Sandset PM. Multidetector computed tomography (MDCT) in the diagnosis of pulmonary embolism: interobserver agreement among radiologists with varied levels of experience. Acta Radiol 2007;48:165–170.
    16. Desai SR. Unsuspected pulmonary embolism on CT scanning: yet another headache for clinicians? Thorax 2007;62:470–472.
    17. Perrier A, Desmarais S, Miron MJ, de Moerloose P, Lepage R, Slosman D, Didier D, Unger PF, Patenaude JV, Bounameaux H. Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet 1999;353:190–195.
    18. Hutchinson BD, Navin P, Marom EM, et al. Overdiagnosis of pulmonary embolism by pulmonary CT angiography. AJR Am J Roentgenol 2015;205:271-277.

     

    1. Gurney JW. No fooling around: direct visualisation of pulmonary embolism. Radiology 1993;188:618–9.
    2. Miller WT Jr, Marinari LA, Barbosa E Jr, et al. Small pulmonary artery defects are not reliable indicators of pulmonary embolism. Ann Am Thorac Soc 2015;12:1022-1029
    3. Courtney DM, Miller CD, Smithline HA, et al. Prospective multicenter assessment of interobserver agreement for radiologist inter- pretation of multidetector CT angiography for pulmonary embo- lism. J Thromb Haemost 2010;8:533–40.
    4. Goodman LR. Small pulmonary emboli: what do we know? Radiology 2005;23:654-8.
    5. Stein PD, Henry JW. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest 1995;108:978–81.
    6. Bergqvist D, Lindblad B. A 30-year survey of pulmonary embolism verified at autopsy: an analysis of 1274 surgical patients. Br J Surg 1985;72:105–8.
    7. Cullen DJ, Nemeskal AR. The autopsy incidence of acute pulmonary embolism in critically ill surgical patients. Intensive Care Med 1986;12:399–403.
    8. Lindblad B, Sternby NH, Bergqvist D. Incidence of venous thromboembolism verified by necropsy over 30 years. BMJ 1991;302:709–11.
    9. Lindblad B, Eriksson A, Bergqvist D. Autopsy- verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988. Br J Surg 1991;78:849–52.
    10. Engelke C, Rummeny EJ, Marten K. Pulmonary embolism at multi-detector row CT of chest: one- year survival of treated and untreated patients. Radiology 2006;239:563–75.
    11. Eyer BA, Goodman LR, Washington L. Clinicians’ response to radiologists’ reports of isolated subsegmental pulmonary embolism or inconclusive interpretation of pulmonary embolism using MDCT. AJR Am J Roentgenol 2005;184:623–8.
    12. den Exter PL, van Es J, Klok FA, Kroft LJ, Kruip MJ, Kamphuisen PW, Büller HR, Huisman MV. Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism. Blood. 2013 Aug 15;122(7):1144-9; quiz 1329.
    13. Buller HR, Prins MH, Lensing AW, et al; EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366(14):1287-1297.
    14. Agnelli G, Buller HR, Cohen A, et al; AMPLIFY- EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013;368(8): 699-708.
    15. Beam DM, Kahler ZP, Kline JA, Hiestand BC. Immediate Discharge and Home Treatment With Rivaroxaban of Low-risk Venous Thromboembolism Diagnosed in Two U.S. Emergency Departments: A One-year Preplanned Analysis. Acad Emerg Med 2015;22(7):788-795.
    16. Remy-Jardin M, Pistolesi M, Goodman LR, Gefter WB, Gottschalk A, Mayo JR, et al. Management of suspected acute pulmonary embolism in the era of CT angiography: a statement from the Fleischner Society. Radiology 2007;245:315-29.
    17. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie N, Pruszczyk P, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008;29:2276-315.
    18. Prasad V, Rho J, Cifu. The diagnosis and treatment of pulmonary embolism. A metaphor for medicine in the evidence-based medicine era. Arch Intern Med 2012;172(12):955–8.
    19. Donato AA, Khoche S, Santora J, Wagner B. Clinical outcomes in patients with isolated subsegmental pulmonary emboli diagnosed by multidetector CT pulmonary angiography. Thromb Res 2010;126:e266-70.
    20. Stein PD, Goodman LR, Hull RD, Dalen JE, Matta F. Diagnosis and management of isolated subsegmental pulmonary embolism: review and assessment of the options. Clin Appl Thromb Hemost 2012;18:20-6.
    21. Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arch Intern Med 2007;167:1414-9.
    22. Hess EP, Knoedler MA, Shah ND, Kline JA, Breslin M, Branda ME, Pencille LJ, Asplin BR, Nestler DM, Sadosty AT, Stiell IG, Ting HH, Montori VM. The chest pain choice decision aid: a randomized trial. Circ Cardiovasc Qual Outcomes 2012 May;5(3):251-9.
    23. Singh B, Mommer SK, Erwin PJ, et al. Pulmonary embolism rule- out criteria (PERC) in pulmonary embolism–revisited: a systematic review and meta-analysis. Emerg Med J 2013;30:701–6.
    24. Fesmire FM, Brown MD, Espinosa JA, et al. Critical issues in the evaluation and management of adult patients presenting to the emergency department with suspected pulmonary embolism. Ann Emerg Med 2011;57:628–52.
    25. Penaloza A, Verschuren F, Dambrine S, et al. Performance of the pulmonary embolism rule-out criteria (the PERC rule) combined with low clinical probability in high prevalence population. Thromb Res 2012;129:e189–93.
    26. Bokobza J, Aubry A, Nakle N, et al. Pulmonary embolism rule-out criteria vs D-dimer testing in low-risk patients for pulmonary em- bolism: a retrospective study. Am J Emerg Med 2014;32:609–13.
    27. Couturaud F, Kearon C, Bates SM, Ginsberg JS. Decrease in sensitivity of D-dimer for acute venous thromboembolism after starting anticoagulant therapy. Blood Coagul Fibrinolysis 2002; 13:241–6.
    28. Taira T, Taira BR, Carmen M, et al. Risk of venous thromboembolism in patients with borderline quantitative D-dimer levels. Am J Emerg Med 2010;28:450–3.
    29. Kutinsky I, Blakley S, Roche V. Normal D-dimer levels in patients with pulmonary embolism. Arch Intern Med 1999;159:1569–72.
    30. Runyon MS, Gellar MA, Sanapareddy N, et al. Development and comparison of a minimally-invasive model of autologous clot pul- monary embolism in Sprague-Dawley and Copenhagen rats. Thromb J 2010;8:3.
    31. Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA, et al. Diagnostic accuracy of conventional or age adjusted d-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. BMJ 2013; 346:f2492.
    32. Righini M, Van Es J, Den Exter PL, Roy PM, Verschuren F, Ghuysen A, et al. Age-adjusted d-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA 2014; 311:1117-24.

Penetrating Trauma: What We Miss and How We Can Improve

Authors: Elliott Chinn, DO (EM Resident Physician at Jacobi Medical Center) and Steve McGuire, DO (EM Chief Resident at Jacobi Medical Center) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM staff physician at SAUSHEC, USAF)

 

During your next shift you hear “Level 1 Trauma in 5 minutes”. The patient arrives. He is a 28 year-old male, stabbed in the chest, with the following vitals: T 98.6 HR 95 BP 105/70 RR 20 PO2 98% RA. He’s talking, you see a 2 cm stab wound to the left subcostal region, his breath sounds are even bilaterally, and his repeat blood pressure is 115/80. He’s moving all of his extremities so you log roll him and see no other injuries. A supine chest x-ray is done which is negative, and a quick FAST is unrevealing. You step away for a brief moment to put in orders when you’re notified that the patient is lethargic and his heart rate jumped to 160. You put on your stethoscope, suspecting to hear decreased breath sounds and when you do, you place a 14g angiocath into his chest and “wwhheeww”, you and your patient release some tension.

What happened? What did you miss and why?

Your next patient is a 50 year-old male with abdominal pain. He doesn’t look so great and doesn’t offer much for medical problems. You notice an old, vertical scar on his chest. “Oh yeah doc, I was stabbed a long time ago”. His labs come back, and he has an elevated WBC and lactate. Hours later, he is in the OR for a strangulated hernia that was in his thorax, a complication of an undiagnosed diaphragmatic injury.

What happened? What did you and the previous doctor miss and why?

Hours later you see another stabbing victim, only this time the wound is just underneath his umbilicus. The puncture doesn’t look that deep, and the patient’s vital signs are stable. While he is complaining of pain, his abdomen doesn’t feel like a surgical abdomen. A CT scan is ordered and when it comes back it is negative. You scratch your head and think to yourself, “Can I send this patient home?”

What are you worried about missing and what can be done to reassure you?

Your next patient is here for left-sided back pain. He was just discharged four days ago after being shot in the stomach. He is febrile, tachycardic, and has no other medical or surgical history aside from his previous trauma. Hours later, your CT scan shows a perinephric abscess, and he’s admitted for IV antibiotics.

What happened? What did the surgeons miss and why?

Our role as ED physicians is to stabilize the patient while determining their disposition. Inevitably, we are going to miss things, as it isn’t our job to diagnose every injury. This post will discuss injuries we can miss related to penetrating trauma in the acute and post-discharge setting.

Case #1: Tension Pneumothorax

Tension pneumothorax (TPTX) is one of the deadliest, cannot miss diagnoses we are responsible for. We are trained to think of pneumothorax when we see respiratory distress, chest pain, and decreased lung sounds, and when paired with hypotension, tachycardia, and dropping PO2, we should reflexively think of tension pneumothorax. Primarily a clinical diagnosis, it should not be diagnosed radiographically.

In the real world, diagnosing a tension pneumothorax, let alone before x-ray, is not as easy as we are led to believe. A review of 18 case reports in awake, non-ventilated patients showed that “classic” signs such as low Sp02, tracheal deviation, and hypotension are found in less than 25% of cases (1). Furthermore, a case series of 115 consecutive tension pneumothoraces in South Africa showed that 25% were missed on initial assessment, with 40% of those patients dying (2). Even more concerning, that series took place in a region that gets 30 cases of tension pneumothorax a year, which is more than most U.S. hospitals see.

That study did not look into why the diagnosis was missed. Perhaps they stopped their diagnosis at pneumothorax because they didn’t see textbook signs that as it turns out, may not be so textbook. So, what can we do to make sure we do not miss this diagnosis?

First, always have a high index of suspicion for tension pneumothorax, taking into account many of the classic signs we are taught to look for are often not present. Second, confirm your clinical exclusion of the diagnosis with ultrasound, as it has been shown to have a higher sensitivity than upright or supine chest radiography and has a negative predictive value approaching 100% (3). Finally, avoid supine CXR at all cost. A recent article showed it has a significantly lower sensitivity than upright, only catching 21% patients with a pneumothorax (4).

Case #2: Diaphragmatic Injury

Missing a diaphragmatic injury will not immediately harm your patient; however, months to decades later it can have devastating consequences if not recognized.

The range of diaphragmatic injuries missed on CT scan ranges anywhere from 12-63%, but more disturbingly, the mortality rate for subsequent complications can be as high as 60% (5,6). One study found complications like herniated stomach, large gut, spleen, liver, and gangrenous gut if there is a delay in presentation, even “fecopneumothorax” if that herniated organ is mistaken for a pleural effusion on chest x-ray and a chest tube is placed (6).

The gold standard for diagnosing diaphragmatic injury is surgery, but in an era of increased nonsurgical management, some of these injures are missed. CT scan lacks the sensitivity and specificity of surgery, so we cannot rule it out with imaging alone. There is a wide range of sensitivity for picking it up on CT. One review article cited a range of 61-87%, while showing that sensitivity is worse when the injury is on the right due to the homogeneity between the liver and diaphragm (5). In one small but well conducted study, patients with penetrating trauma to the left thoracoabdominal area who went to the OR 48 hours after CT scan showed a sensitivity of 82%, with a negative predictive value of 93%.

What can we do as ED physicians to improve?  First, be specific in your indication for why you are getting a CT scan. Traumas can be chaotic environments, and we might overlook the importance of identifying entry points and mechanism when we order imaging which can be valuable clues to radiologists. One might be so bold as to say “rule out diaphragmatic injury” to further clue them in, as there are several direct and indirect signs of diaphragmatic injury on CT, some of which are more common in penetrating trauma.

While a missed diaphragmatic injury isn’t usually at the top of our differential for most chief complaints, it should at least be considered in a patient with a history of thoracoabdominal trauma. It is definitely one with serious morbidity/mortality if left undiagnosed and unfortunately, could present days to years down the line and seem completely unrelated to their past medical history.

Case #3: Hollow Viscus Injury

In penetrating abdominal trauma there are hard signs for going to the OR: hemodynamic instability, evisceration, or peritonitis. What should be done when there are no hard signs has been a matter of debate since the 1960s. In 2009 the Western Trauma Association put out a guideline which was again tested in 2011 that advocates for local wound exploration in stable patients who have anterior abdominal stab wounds (8). Their goal was to bring everyone to the OR who needed to be there while minimizing unnecessary surgery, procedures, and imaging.

Their guidelines were simple: if the patient is stable, perform local wound exploration and if it is positive, admit for serial clinical assessments with a CBC every 8 hours. If the patient deteriorates clinically, they go to the OR. If they were stable for a day then they could be discharged.

If wound exploration was negative then the patient could be discharged, without relying on a negative CT scan or labs.

It should be noted that they had a strict protocol for wound exploration, which required anesthetizing the wound and probing the entire depth. If posterior fascia or peritoneum were violated, it was considered positive.

How did it all pan out? Patients in the protocol group were significantly less likely to get an unnecessary laparotomy, and they were not at increased risk for complications. They were just as likely to be discharged from the ED, and none of them had a CT scan. Patients whose surgeons did not follow the protocol and used imaging or labs to guide their decision had more unnecessary procedures, with increased length of stay in the hospital and more complications. Most patients who went to the OR after being admitted for serial exams went within four hours, with the last patient going at 15 hours, and their rate of complications was not any higher than those who went straight to the OR.

In the past, local wound exploration has gotten a bad reputation. If you are still not a fan of it, you can still skip the reflex to go straight to the CT scanner as long as your patient is stable and your surgical service can observe them. One study found that no injuries were missed when a patient was observed for 24 hours, and those who waited to go to the OR did not have a higher rate of complications than those who went immediately (9). This is important because some clinicians think they can discharge patients home if their CT scans are normal when in fact it could be a false negative.  Additionally, there are cases of false positives on CT that lead to wasteful trips to the OR (8).

The point here has more to do with empowering us to not instinctively take our patients to the CT scan or push our surgeons, unnecessarily, to take our patients to the OR. This is an opportunity to not miss an injury by not doing something, which harms our patients in a way we cannot yet quantify.

To summarize, hollow viscous injury is a diagnosis we can miss if we don’t watch a patient for long enough, and research shows that 24 hours is the longest it will take your patient to deteriorate (9). Local wound exploration could be a tool to let us exclude the diagnosis without having to admit every single patient with penetrating abdominal trauma. We should allow our clinical exam to guide our management, not imaging or lab values.

Case #4: Ureteral Injuries

Surrounded by some significant real estate, the ureters are very well protected. If those organs are involved, a ureteral injury may be missed, so it must be on the differential in any patient who presents shortly after being discharged from a hospitalization related to penetrating injuries.

A well conducted review of ureteral injuries showed they mostly affect men who were victims of penetrating trauma, involved the proximal ureter (defined as from the ureteropelvic junction down to the sacroiliac joint), and actually lacked hematuria, regarded as some to be the hallmark of ureteral injury (10). 90% of the time there will be an associated injury, almost always (96%) bowel injuries.

As with other rare injuries, they require a high index of suspicion. Close to 38% of ureteral injuries can cause complications such as retroperitoneal abscess, infected urinoma, and fistula, but in rare circumstances they can lead to renal failure and sepsis. CT scan by itself isn’t the best way to diagnose it, and even when patients go to the OR it is missed about 40% of the time.

So what can we do to avoid this? In any penetrating trauma patient with hematuria, consider getting GU involved, especially if your patient is going to have to sit in your department . Specially timed CT scans (“delayed excretory phase images”) might be necessary to make the diagnosis in the acute setting. Understand that the absence of hematuria is actually more common in ureteral injuries, so its absence cannot exclude it. If the patient was recently discharged after sustaining penetrating trauma, have a high index of suspicion for this injury, as it could have been missed on initial presentation.

Summary

As ED doctors we play a critical role in trauma. Many of our patients who suffer injuries from penetrating trauma get admitted, ultimately receiving a “trauma tertiary survey” prior to discharge. This is a critical step in their care, and research shows that it transforms many “missed injures” into “delays in diagnosis”, meaning they are caught before they cause a problem (11).

In the acute setting the most important thing we can miss is a tension pneumothorax. Thankfully, ultrasound is accessible and with ultrasound education being integral in most residency training programs, it is only a matter of time until most ED doctors can rule it out nearly 100% of the time.

In the patient with a history of penetrating trauma we need to be aware of two injures that could have been missed: diaphragmatic tears and ureteral injuries. While CT scans can miss asymptomatic tears, they are quite good at diagnosing organs that have herniated through the diaphragm so if you are suspicious of it, order that CT scan. In any patient with abdominal or flank pain, fever, or urinary symptoms who has a history of penetrating trauma, consider ureteral injuries because you may need special imaging to diagnose it.

Finally, despite advances in imaging, hollow viscus injuries continue to be a diagnosis that can be missed in the absence of observation and serial abdominal exams. The utility of local wound exploration will likely be debated for some time, but there is growing evidence that it can be used to exclude hollow viscus injury if done appropriately while saving patients from unnecessary radiation and trips to the OR.

References / Further Reading:

  1. Leigh-Smith SS. Tension pneumothorax – time for a re-think? Emergency medicine journal: EMJ. 2005-01;22:8-16.
  2. Kong VV. Traumatic tension pneumothorax: experience from 115 consecutive patients in a trauma service in South Africa. European journal of trauma and emergency surgery (Munich: 2007). 2016-02;42:55-59.
  3. Nandipati KK. Extended focused assessment with sonography for trauma (EFAST) in the diagnosis of pneumothorax: experience at a community based level I trauma center. Injury. 2011-05;42:511-514.
  4. Ball CC. Occult pneumothoraces in patients with penetrating trauma: Does mechanism matter? Canadian journal of surgery. 2010-08;53:251-255.
  5. Panda AA. Traumatic diaphragmatic injury: a review of CT signs and the difference between blunt and penetrating injury. Diagnostic and interventional radiology (Ankara, Turkey). 2014-03;20:121-128.
  6. Ganie FF. Delayed presentation of traumatic diaphragmatic hernia: a diagnosis of suspicion with increased morbidity and mortality. Trauma monthly. 2013;18:12-16.
  7. Yucel MM. Evaluation of diaphragm in penetrating left thoracoabdominal stab injuries: The role of multislice computed tomography. Injury. 2015-09;46:1734-1737.
  8. Biffl WW. Validating the Western Trauma Association algorithm for managing patients with anterior abdominal stab wounds: a Western Trauma Association multicenter trial. The journal of trauma. 2011-12;71:1494-1502.
  9. Inaba KK. Selective nonoperative management of torso gunshot wounds: when is it safe to discharge? The journal of trauma. 2010-06;68:1301-1304.
  10. Pereira BB. A review of ureteral injuries after external trauma. Scandinavian journal of trauma, resuscitation and emergency medicine. 2010;18:6.
  11. Pfeifer R, Pape H-C. Missed injuries in trauma patients: A literature review. Patient Safety in Surgery. 2008;2:20. doi:10.1186/1754-9493-2-20.

RBC Transfusion in the Emergency Department

Author: Brit Long, MD (@long_brit, EM Staff Physician at SAUSHEC, USAF) and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) // Edited by Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident at SAUSHEC, USAF)

Numerous studies have identified anemia, defined as a hemoglobin (Hgb) less than 12g/dL in females and less than 13g/dL in males, as associated with a poor prognosis in trauma patients, post-operative patients, the elderly, and the critically ill.1-9 Today anemia affects nearly 90% of ICU patients, with approximately 30% possessing a Hgb less than 9 g/dL, and 70% a Hgb less than 12 g/dL upon admission.10-12 For more than one hundred years, the transfusion of red blood cells (RBCs) has been a standard of care for the management of anemia. Approximately 14.5 million units of RBCs are transfused annually in the U.S., with 40% of critically ill patients receiving an average of 2-5 units per hospitalization.13-15

There are multiple etiologies of anemia in the setting of trauma, chronic disease, and critical illness: active hemorrhage, blunted erythropoietin production, inflammatory cytokine production, increased hepcidin levels (resulting in hepatocyte and macrophage iron trapping), iron deficiency, and anemia secondary to underlying disease processes.17

What threshold is used for transfusion?

The question for emergency medicine providers ultimately revolves around the threshold for transfusion. RBC transfusion can increase oxygen delivery and address symptoms related to anemia; however, transfusion may result in fluid overload, transfusion reaction, immunomodulation, multiple organ dysfunction, hypothermia, and coagulopathy.17

Previously, the accepted indications for transfusion were a Hgb ≤ 10 g/dL or hematocrit (Hct) < 30%.15,17-19 Given this publicized metric, transfusions were historically administered to asymptomatic patients in an effort to target the aforementioned Hgb goal (a liberal transfusion strategy). However, recent studies have questioned this liberal transfusion threshold in the setting of sepsis, gastrointestinal (GI) bleeding, ACS (acute coronary syndrome), and trauma, touting the adverse events/reactions associated with transfusions as detailed above.

Today there is little debate regarding the necessity for blood product transfusion in the hemodynamically unstable, critically ill patient with a low Hgb and Hct. In alternative clinical scenarios, however, we often times operate within a gray area. The goals of this post are to provide a summary of the physiologic effects of RBC transfusions, detail inherent properties of donor RBCs, describe RBC products available for transfusion in the U.S., review notable adverse reactions associated with transfusions, and provide evidence-based indications for RBC transfusions in a number of clinical scenarios.

 

Physiologic Effects of RBC Transfusion

Oxygenation is dependent on Hgb concentration, Hgb saturation, oxygen supply, cardiac output, and pulmonary ventilation and perfusion.

Peripheral oxygen delivery occurs predominantly through attachment to Hgb. 20,21 In a healthy adult, the daily production of RBCs is 0.25/kg, with an average RBC lifespan of 120 days.22 While there exists a significant oxygen reservoir (the rate of oxygen delivery exceeds that of oxygen consumption by a factor of four), decreases in Hgb level may manifest as symptoms ranging from shortness of breath to chest pain to syncope.

In the setting of anemia, the body demonstrates a number of physiologic compensatory methods:

  • Increased cardiac output improves end organ perfusion and increases the circulation of intravascular vasodilators which in turn results in increased time for oxygen off-loading. 20,21,23
  • Alterations in gene transcription and expression lead to increased levels of  2,3-diphosphoglycerate (2,3-DPG) thereby improving peripheral oxygen off-loading.20,21,2

Transfusion of RBCs serves as a mechanism of improving peripheral oxygen delivery.

 

Inherent Properties of Donor RBCs

Unlike native RBCs, transfused RBCs have a lifespan of approximately 60 days.22 Transfusion of one unit of RBCs increases Hgb by 1 g/dL and Hct by 3%, however, these levels may not be reached in the setting of occult bleeding, repeated laboratory draws, fever, hypersplenism, immunologic disease, or hemolysis.22-26

Effect of Product Age

While the majority of documented transfusions occur within 16-21 days of processing/storage, regulations allow the storage/utilization of PRBC products for up to 42 days. 11,12 As a consequence of the preservation process, RBCs experience changes in cell wall integrity, and exhibit decreased 2,3-DPG. In fact, levels of 2,3-DPG are depleted within 2 weeks of storage, thereby reducing the aforementioned ability of releasing oxygen to peripheral tissues (decreased 2,3-DPG shifts the oxygen binding-dissociation curve to the left).27-36

So…age matters?

 A 2008 study in the New England Journal of Medicine demonstrated that in patients undergoing cardiac procedures, administration of products stored for a prolonged period vs. short duration (20 days vs. 11 days) was associated with increased mortality (2.8% vs. 1.7%, P=0.004), increased rate of intubation beyond 72 hours (9.7% vs. 5.6%, P<0.001), increased incidence of renal failure (2.7% vs. 1.6%, P=0.003), and increased incidence of sepsis/septicemia (4.0% vs. 2.8%, P=0.01).37 Another study, published by Shimmer et al., followed 492 single center cardiology patients receiving RBCs transfusions (stored for 14 days to 42 days) and noted higher rates of sepsis (4.0% vs. 2.8%, P=0.01), increased requirement for intubation beyond 72 hours (9.7% vs. 5.6%, P<0.001), increased incidence of renal failure (2.7% vs. 1.6%, P=0.003), and increased in-hospital mortality (2.8% vs. 1.7%, P=0.004).38

While the P values are convincing, this literature conflicts with current research demonstrating no effect of product age on patient outcomes, in particular mortality. A 2015 New England Journal of Medicine article, published by Steiner et al., focused again on cardiac patients receiving transfusions (multi-center RCT, n = 1096), and compared transfusion with products less than 10 days post donation versus those greater than 21 days.  Mortality was not statistically significant between groups (p=0.57).39 A second 2015 study, evaluating the age of products transfused in critically ill patients admitted to an ICU (n = 2430), demonstrated that products stored for a mean (±SD) of 6.1±4.9 days as compared with 22.0±8.4 days in the standard-blood group (P<0.001) had no clinically significant effect on mortality, major illness, duration of hospital stay, critical care requirement, or transfusion reaction.40

Where do we go from here?

The most recent Cochrane review notes insufficient literature for the provision of transfusion product age recommendations in patients with acute coronary syndrome, critical illness, trauma, or in the peri-operative state.41 According to the authors, existing studies suffer from extensive heterogeneity, differing definitions of “old” versus “fresh” products, and significant study bias.41

Currently, there is insufficient evidence to suggest that the transfusion of older blood products is associated with adverse patient outcomes.42,43 Several randomized trials are underway with preliminary results indicating no adverse outcomes associated with transfusion of products age <21 days.

 

Types of Products

There are several types of RBC products. Leukoreduced or leukodepleted RBCs are employed to prevent febrile non-hemolytic reactions (induced by the presence of antibodies to white blood cells), to reduce the risk of CMV transmission (especially important in bone marrow transplant patients, pregnant women, and those with HIV/AIDS), and to decrease the risk of transplant rejection.44,45 Washed RBCs are used to prevent allergic reactions, specifically in patients with IgA deficiency, as well as in patients with recurrent severe transfusion reactions not prevented by pre-treatment with antihistamines and corticosteroids.44,45 Irradiated products prevent Transfusion Associated Graft-Versus Host Disease (TAGVHD) through gamma irradiation of blood products.46-49

 

Transfusion Reactions and Infections

Transfusion of RBCs functions as an allogeneic tissue transplantation. Host response to transfusion varies as gene transcription and expression lead to modifications in intrinsic T cell, natural killer cell, and phagocyte function, and alterations in lymphocyte response and cytokine production. This effect is known as transfusion-related immunomodulation (TRIM), which may be associated with increased blood viscosity and decreased cardiac output. 2,3,10,21,24,25,31,48

Additional transfusion reactions include: febrile non-hemolytic transfusion reaction, allergic reaction, acute hemolytic reaction, anaphylactic reaction, transfusion-associated circulatory overload (TACO), transfusion-associated acute lung injury (TRALI), iron overload, delayed hemolytic reaction, and transfusion-associated graft vs. host disease (GVHD). For further discussion, please see references 47-49.

Give the aforementioned list of transfusion complications, the decision to transfuse should not be taken lightly.  The risk of infection occurring secondary to transfusion is also concerning: One meta-analysis found an absolute pooled risk of serious transfusion related infection of 11.8% with a restrictive transfusion strategy versus 16.9% with a liberal strategy.43 The number needed to treat with a restrictive strategy in order to prevent one serious infection was 38.43 In a study focusing on critically ill patients, the nosocomial infection rate in patients receiving RBC transfusion was 24.3%, while amongst the control group not requiring transfusion, nosocomial infections occurred in 10.2%.37

In developed nations with well-regulated supplies, safety of transfusion has drastically improved due to changes in blood screening measures and quality control. In the U.S., the risk of HIV transmission is 1 per 1.5 million and HBV 1 in 357,000 donations.38 Unfortunately, in developing nations the story is different.  With 39 countries lacking systems to test donated units, the prevalence of HIV in low-income nations is 2.3% of the blood products obtained.50-53

 

Transfusion Guidelines

While multiple guidelines for transfusion exist, the most commonly referenced is the American Association of Blood Banks’ (AABB). Other guidelines from the American Society of Anesthesiology, British Committee for Standards in Hematology, European Society of Cardiology, Australian and New Zealand Society of Blood Transfusion, and American College of Physicians offer similar recommendations.54-57 The AABB’s guidelines include the following:58

  1. Adhere to a restrictive transfusion strategy: 7 to 8 g/dL transfusion threshold in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence).
  2. Adhere to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease; consider transfusion for symptomatic patients or those with a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence).
  3. No current recommendation for hemodynamically stable patients with ACS (Grade: uncertain recommendation; very low-quality evidence).
  4. Transfusion decisions should be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).

 

Restrictive versus Liberal Transfusion Threshold: The Studies

If you’re questioning the origin of the 7-8g/dl margin, look no further: AABB recommendations originate in several large clinical trials evaluating transfusion thresholds in various populations including critically ill patients admitted to ICU, those having undergone cardiac surgery, or orthopedic surgery, those experiencing trauma, and those suffering from sepsis, with primary hypotheses that restrictive transfusion strategies were as safe, if not safer, than liberal thresholds.10,15,16,54-58

Perhaps the most commonly cited AABB utilized study is the landmark 1999 Transfusion Requirements in Critical Care (TRICC) trial, completed in euvolemic ICU patients with a Hgb < 9 g/dL within 72 hours of admission. Patients were randomized to a restrictive (7 g/dL) or liberal transfusion (10 g/dL) strategy. The TRICC trial revealed no significant difference in all-cause mortality at 30 days (Restrictive 18.7%, Liberal 23.3% (95% CI -0.84 – 10.2%, p = 0.11)), however as a secondary outcome, mortality during hospitalization was found to be lower in the restrictive transfusion group.10

A second study cited by the AABB, The Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS) trial included 2,016 patients > 50 years of age having undergone hip arthroplasty, and found no mortality benefit or improvement in return to ambulation with a restrictive (8 g/dL) versus liberal (10g/dL) transfusion threshold.59 Finally, The CRIT study (2004) conducted in intensive care units, demonstrated increased mortality with increasing number of RBC transfusions.11

What do other sources have to say about liberal vs. restrictive transfusion strategies?

A 2012 Cochrane review found restrictive transfusion strategies to be associated with reduced in-hospital mortality, (RR 0.77, 95% CI 0.62-0.95) but not 30 day mortality (RR 0.85, 95% CI 0.70 to 1.03). The strategy did not affect patient length of stay or functional recovery, and ultimately, although the authors recommend use of a restrictive strategy, the review cautions readers regarding the use of a restrictive strategy for patients with acute coronary syndrome.60 A second Cochrane review identified restrictive strategies as reducing infection (RR 0.76; 95% CI 0.60 to 0.97), but not affecting mortality, rates of cardiac events or stroke, or lengths of stay.61

A recently published meta-analysis found a restrictive threshold of 7 g/dL associated with reduced in-hospital mortality (risk ratio [RR], 0.74; confidence interval [CI], 0.60-0.92), total mortality (RR, 0.80; CI, 0.65-0.98), re-bleeding (RR, 0.64; CI, 0.45-0.90), acute coronary syndrome (RR, 0.44; CI, 0.22-0.89), pulmonary edema (RR, 0.48; CI, 0.33-0.72), and bacterial infections (RR, 0.86; CI, 0.73-1.00), with a NNT of 33 to prevent one death.62

A British Medical Journal meta-analysis evaluated 31 trials with 9813 patients.  Similar to the Cochrane reviews, no difference in morbidity, mortality, and myocardial infarction was found when comparing liberal and restrictive transfusion strategies.  However, they did find reduced incidence of infection with a restrictive transfusion strategy.63

Ultimately it would seem that a restrictive transfusion strategy is correlated with decreased in-hospital mortality and decreased rates of infection.  But does this translate to all populations?

 

Transfusion in Special Populations: The Studies

Sepsis/Critically Ill

The care of patients with sepsis underwent a revolution with Early Goal Directed Therapy (EGDT) in 2001, in which blood transfusion became a central component. The Surviving Sepsis Guidelines advised transfusion to Hgb of 10 g/dL or Hct of 30% during the first 6 hours of resuscitation if hypoperfusion persisted despite fluid resuscitation and pressor support.64

This threshold has subsequently been questioned due to its basis in weak observational evidence.   Enter the TRISS trial:  The TRISS trial enrolled approximately 1000 patients with septic shock with a Hgb < 9 g/dL. Participants underwent randomization to one of two groups: one with a transfusion threshold of 7 g/dL and the other with a threshold of 9 g/dL. If patients met the threshold, 1 unit of leukoreduced RBCs was transfused. The investigators found that the primary outcome of death up to 90 days post transfusion did not differ between the groups (43% and 45%, RR 0.94 with 95% CI 0.78-1.09). Secodary outcomes including the use of life support, mechanical ventilation, vasopressor support, and renal replacement therapy were also equivalent between groups. As the restrictive group ultimately received fewer total PRBC units, the authors suggested that avoiding unnecessary transfusions conserved resources, and reduced the risk of infection or immune reaction secondary to tranfusion.70

More recent ground breaking studies, The ProCESS trial (2014) and ARISE study both revealed no difference in clinical outcomes according to threshold transfusion levels:

The ProCESS trial compared original EGDT to a group with a less invasive protocol that required transfusion for Hgb < 7.5 g/dL, and a group with treatment left at discretion of the treating physician. The EGDT group underwent transfusion at a rate of 14.4%, approximately double that of the other groups. As mentioned above, no difference in clinical outcomes was discovered.66 The ARISE study compared EGDT with usual care. Again, the EGDT group underwent double the transfusion frequency when compared to the group undergoing usual care, with no difference in outcomes.67

With the support from these studies, a transfusion threshold of 7 g/dL in patients with septic shock is advised.58,65

GI Bleeding

The studies evaluating transfusion threshold in patients with GI bleeding provide important information, as investigations were performed in patients with active hemorrhage. The TRICC and TRISS trials did not evaluate this subset of patients.10,65 Villanueva et al. evaluated adults with hematemesis or melena randomized to a restrictive strategy (7 g/dL) versus 9 g/dL. This trial excluded patients with minor bleeding or massive bleeding (defined by exsanguination), and patients with concern for acute coronary syndrome. All patients underwent endoscopy within six hours of presentation. Patients in the restrictive group demonstrated lower mortality versus the liberal group (5% and 9%, P=0.02). The rate of bleeding was also lower in the restrictive group (10% and 16%, P=0.01), with less products transfused.68 In the setting of nonvariceal bleeding, re-bleeding was found to occur at increased rates in patients receiving transfusion (23.6% versus 11.3%, P < 0.01).69 In this same group, 30 day mortality was notably higher (6.8% versus 3.7%, P = 0.005).69

A second study in the UK enrolled patients 18 years and older with upper GI bleeding, randomizing patients to restrictive (8 g/dL) and liberal (10 g/dL) thresholds, with no difference in clinical outcomes.70

Outcomes of these trials are supported by a meta-analysis evaluating studies with restrictive versus liberal transfusions for upper GI bleeding. This meta-analysis found restrictive transfusion groups had decreased death rates (OR 0.26, 95% CI: 0.03-2.10, P = 0.21), shorter hospital stays, (standard mean difference: -0.17, 95% CI: -0.30–0.04, P = 0.009).71

Why do transfusions potentially worsen outcomes in GI bleeding? It is hypothesized that transfusion counteracts the splanchnic vasoconstriction occurring in hypovolemia, thereby increasing pressure in the splanchnic circulation, and impairing clot formation. Transfusion itself is also known to alter coagulation properties. The concept of hemostatic resuscitation is paramount in these patients. Restrictive transfusion strategies decrease the number of transfusions and may directly impact mortality.67,69,70

Restrictive transfusion in the setting of GI bleeding is recommended, with a transfusion threshold of 7 g/dL.

Acute Myocardial Ischemia (AMI)

Data regarding transfusion paramaters in the setting of myocardial ischemia is significantly limited. What we do know is that myocardial oxygen demands are high in the setting of ischemia, and during anemic states, oxygen delivery increases through stroke volume and heart rate, potentially worsening ischemia.72 While this may seem a clear indication for transfusion, the transfusion associated risks of circulatory overload and increased thrombogenicity must also be considered.57,58

As previously cited, the AABB does not identify a transfusion threshold in myocardial ischemia.58

A randomized trial (n = 110) comparing transfusion triggers in patients with AMIs identified increased rates of unscheduled revascularization, death, and recurrent MIs within 30 days of transfusion in patients having been assigned a restrictive transfusion protocol (10.9% in the liberal group and 25.5% in the restrictive group; risk difference 15%, 95%; CI 0.7% to 29.3%), leading the authors to hypothesize that a liberal transfusion strategy in this population is associated with decreased cardiac events and death.72,74

However, these results conflict with numerous current studies. A review of 24,000 patients in the GUSTO IIb, PURSUIT, and PARAGON B trials found an increased risk of death 30 days post transfusion (adjusted hazard ratio, 3.94; 95% CI, 3.26 to 4.75) in patients transfused in the setting of cardiac disease/ischemia.74 A meta-analysis performed by Chatterjee et al. (JAMA, 2013; n = 200,000) revealed increased all-cause mortality with a strategy of product transfusion (18.2%) as compared to no transfusion (10.2%), risk ratio 2.91 (95% ICI 2.46-3.44, P < 0.001). A number needed to harm of 8 identified. Transfusion was associated with higher mortality independent of baseline Hgb, nadir Hgb, and change in Hgb during the hospitalization.75

Current studies conducted in patients experiencing myocardia ischemia suffer from a number of isssues: confounding factors such as anti-platelet agents, varying transfusion thresholds, and differing primary outcomes. As stated previously, the AABB has not published recommendations for this population in regards to transfusion thresholds.63 The meta-analysis detailed above has provided the best data to date, with suggestions of risk with transfusion. Further trials are needed in this population, but a restrictive threshold of 7 g/dL is likely safe if the patient is hemodynamically stable.

Trauma

Most physicians would agree that transfusion is required in the setting of life-threatening trauma with massive hemorrhage. Hgb levels in active hemorrhage do not accurately predict RBC mass, and anemia is often only discovered when non-RBC fluid replacement is provided. The PROPPR trial evaluated the ratio of blood products in massive transfusion. A ratio of 1:1:1 platelet to plasma to RBC transfusion strategy was associated with decreased death by exsanguination in the first 24 hours and increased chance of hemostasis on post-hoc analysis when compared to a ratio of 1:1:2, though the primary outcome of 24 hour and 30 day mortality did not differ.76

In major trauma victims not undergoing massive transfusion, RBC transfusion has been associated with increased mortality, lung injury, infection rates, multiple organ failure, and renal injury.77,78 Brakenridge et al. found an association between increased RBC transfusion ( >9.5 units) with multiple organ dysfunction (OR of 1.91).77

A 2008 study evaluated the relationship between transfusion and patient outcomes including mortality, infection rate, ICU admission, and length of mechanical ventilation: Patients receiving transfusion had higher rates of infection (34% versus 9.4%), inpatient mortality (21.4% versus 6.5%), ICU admission (74% versus 26%), and duration of mechanical ventilation. Patients requiring transfusion had higher injury severity scales, lower GCS scores, and were more advanced in age. When adjustments were made for these variables, infection was found to increase as the number of units transfused increased (OR 2.8).79 Of note: Fresh frozen plasma transfusion has been associated with greater risk of multiple organ failure, as compared to RBCs, potentially confounding study results.78   

One trial, published by McIntyre et al. in the Journal of Trauma (2004; n = 203) evaluated transfusion strategies for critically ill trauma patients utilizing restrictive and liberal thresholds of 7g/dL and 10g/dL respectively.18 Utilizing these parameters, McIntyre and his team discovered that mortality, multiple organ dysfunction, and length of stay were similar between the two groups.18

At this time, resuscitation of the trauma patient with hemorrhage should be based upon clinical status, not laboratory values. Transfusion is warranted in the setting of acute hemorrhagic shock. Once the patient is hemodynamically stable, transfusion should be considered in the setting of symptomatic anemia (chest pain, shortness of breath, poor distal perfusion).

 

Future Directions

As the brain and spinal cord have little anaerobic reserve and are not able to compensate for decreased oxygen delivery, the central nervous system relies on a consistent metabolic supply of oxygen.79 Studies in traumatic brain injury and subarachnoid hemorrhage have suggested utilizing a transfusion threshold of Hgb 8-9 g/dL, but further information is needed to develop true transfusion recommendations.78,79

A subgroup analysis of the TRICC trial analyzed patients with moderate and severe head injury, with transfusion thresholds of 7 g/dL and 10 g/dL. Similar to previous findings and suggestions, no difference in mortality, multiple organ dysfunction, and hospital length of stay were found in this retrospective subgroup analysis.83 A 2016 meta-analysis evaluating RBC transfusion in patients with traumatic brain injury, found no difference in mortality with transfusion threshold varying from Hgb 6-10 g/dL.84

 

Conclusions

As the AABB guidelines are ambiguous, emergency physicians should consider transfusion thresholds and weigh the risks and benefits of transfusion. If the patient is hemodynamically stable and asymptomatic, a Hgb of 7 g/dL is safe. If the patient is hemodynamically unstable and anemic, transfusion may assist the provider in stabilizing the patient.

Summary

– The transfusion threshold of 10 g/dL has recently been questioned, as RBC transfusion is not without risks (transfusion reaction, infection, and potentially increased mortality).

– The AABB currently recommends a transfusion threshold of 7 g/dL Hgb, though studies evaluating transfusion are small in sample size, retrospective, and observational in nature, affecting their applicability.

Age of products transfused likely has no effect on products administered prior to 21 days of storage, though further study is required.

– A hemoglobin level of 7 g/dL is safe in the setting of critical illness, sepsis, gastrointestinal bleeding, and trauma.

– The clinician at the bedside should evaluate the patient for symptoms associated with anemia and transfuse based on risks and benefits.

 

References/Further Reading:

  1. Emmanuel JE, McClelland B, Page R, editors. The Clinical use of Blood in Medicine, Pediatrics, Surgery, Anesthesia, Trauma & Burns. World Health Organization. 1997. p.337.
  2. Balducci L. Anemia, fatigue and aging. Transfus Clin Biol 2010;17:375–81.
  3. Terekeci HM, Kucukardali Y, Onem Y, Erikci AA, Kucukardali B, Sahan B, et al. Relationship between anaemia and cognitive functions in elderly people. Eur J Intern Med 2010;21:87–90.
  4. Chaves PH, Xue QL, Guralnik JM, Ferrucci L, Volpato S, Fried LP. What constitutes normal hemoglobin concentration in community dwelling disabled older women? J Am Ger Soc 2004;52:1811–6.
  5. Musallam KM, Tamim HM, Richards T, Spahn DR, Rosendaal FR, Habbal A, Khreiss M, Dahdaleh FS, Khavandi K, Sfeir PM, et al. Preoperative anaemia and postoperative outcomes in non-cardiac surgery: a retrospective cohort study. Lancet 2011;378:1396–1407.
  6. Sabatine MS, Morrow DA, Giugliano RP, Burton PB, Murphy SA, McCabe CH, Gibson CM, Braunwald E. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation 2005;111:2042–2049.
  7. Ripollés Melchor J, Casans Francés R, Espinosa A, Martínez Hurtado E, Navarro Pérez R, Abad Gurumeta A, Basora M, Calvo Vecino JM. Restrictive versus liberal transfusion strategy for red blood cell transfusion in critically ill patients and in patients with acute coronary syndrome: a systematic review, meta-analysis and trial sequential analysis. Minerva Anestesiol. 2015 Jul 22. [Epub ahead of print].
  8. Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999;340:409–417.
  9. Marik PE, Corwin HL. Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature. Crit Care Med 2008;36:2667–2674.
  10. Corwin HL, Surgenor SD, Gettinger A. Transfusion practice in the critically ill. Crit Care Med 2003;31:S668–S671.
  11. Corwin HL, Gettinger A, Pearl RG, Fink MP, Levy MM, Abraham E, MacIntyre NR, Shabot MM, Duh MS, Shapiro MJ. The CRIT Study: Anemia and blood transfusion in the critically ill–current clinical practice in the United States. Crit Care Med 2004;32:39–52.
  12. Walsh TS and Saleh E. Anaemia during critical illnessBr. J. Anaesth 2006;97(3):278-291.
  13. U.S. Department of Health and Human Services. The 2009 national blood collection and utilization survey report. Washington, DC: U.S. Department of Health and Human Services, Office of the Assistant Secretary for Health; 2011.
  14. Vincent JL, Baron JF, Reinhart K, Gattinoni L, Thijs L, Webb A, Meier-Hellmann A, Nollet G, Peres-Bota D. Anemia and blood transfusion in critically ill patients. JAMA 2002;288:1499–1507.
  15. Blood Observational Study Investigators of ANZICS-Clinical Trials Group, Westbrook A, Pettilä V, Nichol A, Bailey MJ, Syres G, Murray L, Bellomo R, Wood E, Phillips LE, Street A, French C, Orford N, Santamaria J, Cooper DJ. Transfusion practice and guidelines in Australian and New Zealand intensive care units. Intensive Care Med 2010;36:1138–1146.
  16. Napolitano LM, Kurek S, Luchette FA, Corwin HL, Barie PS, Tisherman SA, Hebert PC, Anderson GL, Bard MR, Bromberg W, Chiu WC, Cipolle MD, Clancy KD, Diebel L, Hoff WS, Hughes KM, Munshi I, Nayduch D, Sandhu R, Yelon JA; American College of Critical Care Medicine of the Society of Critical Care Medicine; Eastern Association for the Surgery of Trauma Practice Management Workgroup. Clinical practice guideline: red blood cell transfusion in adult trauma and critical care. Crit Care Med 2009 Dec;37(12):3124-57.
  17. Blair SD, Janvrin SB, McCollum CN, Greenhalgh RM. Effect of early blood transfusion on gastrointestinal haemorrhage. Br J Surg 1986;73:783-785.
  18. McIntyre L, Hebert PC, Wells G, et al. Is a restrictive transfusion strategy safe for resuscitated and critically ill trauma patients? J Trauma 2004;57:563-568.
  19. Bracey AW, Radovancevic R, Riggs SA, et al. Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome. Transfusion 1999;39:1070-1077.
  20. Finch CA, Lenfant C. Oxygen transport in man. N Engl J Med 1972;286:407–415.
  21. Hameed SM, Aird WC. Oxygen delivery. Crit Care Med 2003;31:S658-67.
  22. Liumbruno G, Bennardello F, Lattanzio A, Piccolli P, Roseetti G. Recommendations for the transfusion of red blood cells. Blood Transfus 2009;7:49-64.
  23. Hebert PC, Van der Linden P, Biro G, Hu LQ. Physiologic aspects of anemia. Crit Care Clin 2004;20:187-212.
  24. Clinical practice guidelines on the use of blood components (red blood cells, platelets, fresh frozen plasma, cryoprecipitate). Endorsed September 2001. National Health and Medical Research Council, Australasian Society of Blood Transfusion Inc. Available at: http://www.nhmrc.gov.au/publications/ synopses/_files/cp78.pdf.
  25. Practice guidelines for blood transfusion: a compilation from recent peer-reviewed literature. American Red Cross 2002. Available at: http://chapters.redcross.org/ br/indianaoh/hospitals/transfusion guidelines.htm.re.
  26. Elzik ME, Dirschl DR, Dahners LE. Correlation of transfusion volume to change in hematocrit. Am J Hematol 2006;81:145-6.
  27. Zou S, Dorsey KA, Notari EP, Foster GA, Krysztof DE, Musavi F, et al. Prevalence, incidence, and residual risk of human immunodeficiency virus and hepatitis C virus infections among United States blood donors since the introduction of nucleic acid testing. Transfusion 2010;50(7):1495–504
  28. Chin-Yee I, Arya N, d’Almeida MS. The red cell storage lesion and its implication for transfusion. Transfus Sci 1997;18:447–458.
  29. Card RT, Mohandas N, Perkins HA, Shohet SB. Deformability of stored red blood cells. Relationship to degree of packing. Transfusion 1982;22:96–101.
  30. Karam O, Tucci M, Toledano BJ, Robitaille N, Cousineau J, Thibault L, Lacroix J, Le Deist F. Length of storage and in vitro immunomodulation induced by prestorage leukoreduced red blood cells. Transfusion 2009;49:26–2334.
  31. Rana R, Fernandez-Perez ER, Kahn SA, et al. Transfusion-related acute lung injury and pulmonary edema in critically ill patients: A retrospective study. Transfusion 2006;46:1478–1483
  32. Li G, Daniels CE, Kojicic M, et al. The accuracy of natriuretic peptides in the differentiation between transfusion-related acute lung injury and transfusion-related circulatory overload in the critically ill. Transfusion 2009;49:13–20.
  33. Skeate RC, Easlung T. Distinguishing between transfusion-related acute lung injury and transfusion-associated circulatory overload. Curr Opin Hematol 2007;14:682– 687.
  34. Ho J, Sibbald WJ, Chin-Yee IH. Effects of storage on efficacy of red cell transfusion: When is it not safe? Crit Care Med 2003;31(12 Suppl):S687–S697.
  35. Almac E, Ince C. The impact of storage of red cell function in blood transfusion. Best Pract Res Clin Anaesthesiol 2007;21:195–208.
  36. Offner PJ. Age of blood: Does it make a difference? Crit Care 2004;8(Suppl 2):S24 –S26.
  37. Koch CG, Li L, Sessler DI, Figueroa P, Hoeltge GA, Mihaljevic T, Blackstone EH. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med 2008 Mar 20;358(12):1229-39.
  38. Shimmer C, Hamouda K, Özkur M, et al. Influence of storage time and amount of red blood cell transfusion on postoperative renal function: an observational cohort study. Heart, Lung and Vessels 2013;5(3):148-157.
  39. Steiner ME, Ness PM, Assmann SF, Triulzi DJ, Sloan SR, Delaney M, Granger S. Effects of red-cell storage duration on patients undergoing cardiac surgery. N Engl J Med 2015 Apr 9;372(15):1419-29.
  40. Lacroix J, Hébert PC, Fergusson DA, Tinmouth A, Cook DJ, Marshall JC, Clayton L, McIntyre L, Callum J, Turgeon AF, Blajchman MA, Walsh TS, Stanworth SJ, Campbell H, Capellier G, Tiberghien P, Bardiaux L, van de Watering L, van der Meer NJ, Sabri E, Vo D; ABLE Investigators; Canadian Critical Care Trials Group. Age of transfused blood in critically ill adults. N Engl J Med 2015 Apr 9;372(15):1410-8.
  41. Brunskill SJ, Wilkinson KL, Doree C, Trivella M, Stanworth S. Transfusion of fresher versus older red blood cells for all conditions. Cochrane Database of Systematic Reviews 2015, Issue 5. Art. No.: CD010801. DOI: 10.1002/14651858.CD010801.pub2.
  42. Aubron C, Nichol A, Cooper DJ, Bellomo R. Age of red blood cells and transfusion in critically ill patients. Annals of Intensive Care 2013;3:2.
  43. Rohde JM, Dimcheff DE, Blumberg N, et al. Health Care–Associated Infection After Red Blood Cell Transfusion: A Systematic Review and Meta-analysis. JAMA 2014;311(13):1317-1326.Elzik ME, Dirschl DR, Dahners LE. Correlation of transfusion volume to change in hematocrit. Am J Hematol 2006;81:145-6.
  44. Topics in transfusion medicine. Guidelines. Irradiated blood products. Leucocyte depletion of blood and blood components. Australasian Society of Blood Transfusion Inc. October 1996. Available at: http:// www.anzsbt.org.au/publications/documents/1996_Vol3_2.pdf
  45. Council of Europe. Guide to the Preparation, Use and Quality Assurance of Blood Components. Recommendation No R (95) 15 on the Preparation, Use and Quality Assurance of Blood Components, 14th ed, Strasbourg, Council of Europe Press; 2008.
  46. Guidelines for gamma irradiation of blood components. Revised 2003. Australian & New Zealand Society of Blood Transfusion Inc. Australian Red Cross Blood Service, New Zealand Blood Service. Available at: http://www.anzsbt.org.au/ publications/documents/ANZSBTguide_May03.pdf.
  47. Gorlin JB, Minz PD. Transfusion-associated graft-vs- host disease. In: Mintz PD editor. Transfusion Therapy: Clinical Principles and Practice, Bethesda, MD: AABB; 2005. p.579-96.
  48. Vamvakas EC, Blajchman MA. Transfusion-related immunomodulation (TRIM): an update. Blood Rev 2007 Nov;21(6):327-48.
  49. Pineda AA, Taswell HF. Transfusion reactions associated with anti-IgA antibodies: report of four cases and review of the literature. Transfusion Jan-Feb 1975;15(1):10-5
  50. Goodnough LT, Shander A. Risks and complications of blood transfusions: optimizing outcomes for patients with chemotherapy-induced anemia. Advanced Studies in Medicine 2008;8(10):357–62.
  51. Kitchen AD, Barbara JAJ. Current information on the infectious risks of allogeneic blood transfusion. Transfusion Alternative in Transfusion Medicine 2008;10:102–11.
  52. Klein HG, Spahn DR, Carson JL. Red blood cell transfusion in clinical practice. Lancet 2007;370(9585):415–26.
  53. Zou S, Stramer SL, Notari EP, Kuhns MC, Krysztof D, Musavi F, et al. Current incidence and residual risk of hepatitis B infection among blood donors in the United States. Transfusion 2009;49(8):1609–20.
  54. Practice guidelines for blood component therapy: a report by the American Society of Anesthesiologists Task Force on Blood Component Therapy. Anesthesiology 1996;84:732-47.
  55. Murphy MF, Wallington TB, Kelsey P, Boulton F, Bruce M, Cohen H, et al; British Committee for Standards in Haematology, Blood Transfusion Task Force. Guidelines for the clinical use of red cell transfusions. Br J Haematol 2001;113:24-31.
  56. National Health and Medical Research Council/Australasian Society of Blood Transfusion. Clinical Practice Guidelines: Appropriate Use of Red Blood Cells. Sydney, Australia: National Health and Medical Research Council/Australasian Society of Blood Transfusion; 2001.
  57. Bassand JP, Hamm CW, Ardissino D, Boersma E, Budaj A, Fernandez-Aviles F, et al; Task Force for Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of European Society of Cardiology. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J 2007;28:1598-660.
  58. Carson JL, Terrin ML, Noveck H, Sanders DW, Chaitman BR, Rhoads GG, et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med 2011;365:2453–62.
  59. Carson JL, Terrin ML, Noveck H, Sanders DW, Chaitman BR, Rhoads GG, et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med 2011;365:2453–62.
  60. Carson JL, Carless PA, Herbert PC. Transfusion thresholds and other strategies for guiding allogenic red blood cell transfusion. The Cochrane database of systematic reviews. 2012;4:CD002042. doi:10.1002/12651858.CD002042.pub3.
  61. Carless PA, Henry DA, Carson JL, Herbert PPC, McClellandB, Ker K. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database of Systematic Reviews 2010, Issue 10. Art. No.:CD002042. do:10.1002/14651858.CD002042.pub2.
  62. Salpeter SR, Buckley JS, Chatterjee S. Impact of more restrictive blood transfusion strategies on clinical outcomes: a meta-analysis and systematic review. Am J Med. 2014 Feb; 127 (2):124-131.e3.
  63. Holst LB, Petersen MW, Haase N, Perner A, Wetterslev J. Restrictive versus liberal transfusion strategy for red blood cell transfusion: systematic review of randomised trials with meta-analysis and trial sequential analysis. BMJ: British Medical Journal 2015;350:h1354.
  64. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77.
  65. Holst LB, Haase N, Wetterslev J, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 2014;371:1381-91.
  66. The ProCESS Investigators. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014;370:1683-93.
  67. The ARISE Investigators and the ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014 Oct 16;371(16):1496-506.
  68. Villanueva C, Colomo A, Bosch A, Concepcion M, Hernandez-Gea V, Aracil C, Graupera I, Poca M, Alvarez-Urturi C, Gordillo J, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013; 368:11-21.
  69. Restellini S, Kherad O, Jairath V, Martel M, Barkun N. Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding. Aliment Pharmacy There 2-13;37:316-22.
  70. Jairath V, Kahan BC, Gray A, Doré CJ, Mora A, James MW, Stanley AJ. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet 2015 Jul 11;386(9989):137-44.
  71. Wang J, Bao Y-X, Bai M, Zhang Y-G, Xu W-d, et al. A meta-analysis of randomized controlled trials. World Journal of Gastroenterology; WJG 2013;19(40):6919-6927.
  72. Levy PS, Kim SJ, Eckel PK, Chavez R, Ismail EF, Gould SA, et al. Limit to cardiac compensation during acute isovolemic hemodilution: influence of coronary stenosis. Am J Physiol 1993;265:H340–9.
  73. Cooper HA, Rao SV, Greenberg MD, et al. Conservative vs liberal red cell transfusion in acute myocardial infarction (the CRIT Randomized Pilot Study). Am J Cardiol 2011;108(8):1108–1111.
  74. Rao SV, Jollis JG, Harrington RA, Granger CB, Newby LK, Armstrong PW, et al. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA 2004;292:1555–62.
  75. Chatterjee S, Wetterslev J, Sharma A, Lichstein E, Mukherjee D. Association of Blood Transfusion with increased mortality in myocardial infarction: A meta-analysis and diversity adjusted study sequential analysis. JAMA Intern Med 2013;173(2):132-139.
  76. Baraniuk S, Tilley BC, del Junco DJ, Fox EE, van Belle G, Wade CE, Podbielski JM, Beeler AM, Hess JR, Bulger EM, Schreiber MA, Inaba K, Fabian TC, Kerby JD, Cohen MJ, Miller CN, Rizoli S, Scalea TM, O’Keeffe T, Brasel KJ, Cotton BA, Muskat P, Holcomb JB; PROPPR Study Group. Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial: design, rationale and implementation. Injury 2014 Sep;45(9):1287-95.
  77. Brakenridge SC, Phelan HA, Henley SS, Golden RM, Kashner TM, Eastman AE, Sperry JL, Harbrecht BG, Moore EE, Cuschieri J, Maier RV, Minei JP. Inflammation and the Host Response to Injury Investigators. Early blood product and crystalloid volume resuscitation: risk association with multiple organ dysfunction after severe blunt traumatic injury. J Trauma 2011 Aug;71(2):299-305.
  78. Johnson JL, Moore EE, Kashuk JL, et al. Effect of Blood Products Transfusion on the Development of Postinjury Multiple Organ Failure. Arch Surg 2010;145(10):973-977.
  79. Bochicchio GV, Napolitano L, Joshi M, et al. Outcome analysis of blood product transfusion in trauma patients: a prospective, risk-adjusted study. World J Surg 2008;32:2185–2189.
  80. LeRoux P. Haemoglobin management in acute brain injury. Curr Opin Crit Care 2013;19:83–91.
  81. Diedler J, Sykora M, Hahn P, Heerlein K, Schölzke MN, Kellert L, et al. Low hemoglobin is associated with poor functional outcome after non-traumatic, supratentorial intracerebral hemorrhage. Crit Care 2010;14:R63.
  82. Oddo M, Milby A, Chen I, Frangos S, MacMurtrie E, Maloney-Wilensky E, et al. Hemoglobin concentration and cerebral metabolism in patients with aneurysmal subarachnoid hemorrhage. Stroke 2009;40:1275–81.
  83. McIntyre LA, Fergusson DA, Hutchison JS, Pagliarello G, Marshall JC, Yetisir E, Hare GM, Hébert PC. Effect of a liberal versus restrictive transfusion strategy on mortality in patients with moderate to severe head injury. Neurocrit Care 2006;5(1):4-9.
  84. Boutin A, Chassé M, Shemilt M, Lauzier F, Moore L, Zarychanski R, Griesdale D, et al. Red Blood Cell Transfusion in Patients With Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Transfus Med Rev 2016 Jan;30(1):15-24.

 

The Clinical Decision Rules Series (Part 3): Clinical Pathway Use

Authors: Brit Long, MD (@long_brit, EM physician at SAUSHEC, USAF) and Barry Sheridan, DO (EM Staff Physician and Professor at SAUSHEC) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) & Justin Bright, MD (@JBright2021)

Case:

A 42–year-old male presents with dull chest pain for 4 hours, which worsens with exertion. He has a history of hypertension, and he does not smoke. His VS are normal, as is the physical exam and ECG. He has no risk factors for PE or dissection, and the chest xray is normal as well.  Your first troponin comes back negative. What is this patient’s disposition? Is there any way to avoid admitting or placing this patient into the observation unit for stress testing?

ecg1
From http://www.ecglibrary.com/norm.php

Background:

Clinical decision rules (CDR) can improve decision-making in specific situations in the ED, potentially decreasing further testing and improving disposition times. This part of the CDR series will look in detail at a current clinically significant CDR and pathway – The HEART pathway.

Part one of this series listed the essentials a CDR should possess: answers a relevant question, addresses a common clinical problem, appropriately derived, externally validated, improves clinical practice, applicable to practice and patients, and ease of use. http://www.emdocs.net/clinical-decision-rules-part-1/

Part two examined applying a CDR to actual clinical practice, which involved several steps: determining the rule that would most affect patient care in your setting, identify obstacles to implementation (provider and institution), achieving buy-in (from all members of the team including nurses and other specialties/consultants), publicizing pathway use, and monitoring and refinement of the rule once in place.  http://www.emdocs.net/clinical-decision-rules-part-2/

Part 3 will evaluate actual risk of missed MI in chest pain patients, followed by a look at several clinical rules and pathways.

Risk:

Chest pain accounts for 10% of ED visits. Up to 10 million visits per year and $10 to $12 billion per year in healthcare expenditures are due to chest pain.1-6 The etiology of these presentations can range from benign to life-threatening, and ACS is a major concern. Many of these patients do not possess a cardiac etiology, and patients lacking evidence of ischemia demonstrate low risk of adverse outcomes.1,5,6 However, the ED evaluation of chest pain can present significant medicolegal risk. Approximately 20% of lawsuits are due to diagnosis and management of ACS, and missed myocardial infarction (MI) is one of the highest costs to insurers.2,7-10

The true rate of misdiagnosis approximates 0.2%, rather than the commonly quoted 2% from a study by Pope et al. in 2000.2  In 1996, Goldman et al. suggested that patients without hypotension, heart failure, known prior myocardial infarction, or worsening chest pain had less than 1% risk of death, need for revascularization, or acute coronary syndrome.11 A recent 2015 article by Weinstock et al. found that with two negative troponin tests and nonischemic ECG, the primary outcome of adverse cardiac event occurred in 0.18% of admissions.12 

Clinical decision rule/pathways:

Several clinical decision aids have been developed with the intent of risk stratification for chest pain. The objective of these aids is to place patients into risk categories based on a combination of separate factors, allowing proper selection for discharge, further testing, or intervention. A sensible, safe, and consistent pathway can assist with appropriate disposition, while minimizing patient harm.  The first decision aid was published in 1982 by Goldman et al. using a computer-based algorithm.13 This pathway addressed diagnosis of MI and need for cardiac care unit (CCU) admission.13 Later investigators have sought an aid to appropriately risk stratify patients appropriate for discharge. This review will examine several of the most commonly utilized decision aids.

Thrombolysis In Myocardial Infarction (TIMI) score

The TIMI score was first published in 2000, followed by validation in 2006.14 Initial studies evaluated patients at high-risk for unstable angina and non-ST-elevation MI. This score incorporates several elements based on a 7-point scale, shown below.15-17 Scores of 0-1 points result in a 4.7% risk of ACS, while scores of 6-7 are associated with 40.9% risk.15-18  Validation in separate cohorts demonstrated similar rates of increasing risk for cardiac outcomes with increasing TIMI score.  Sanchis et al. proposed a risk score based on the original TIMI score with troponin, with a primary outcome of death or AMI within one year.19 A small subset of the evaluated population, 17%, were deemed very low risk based on a score of 0. However, patients categorized as low risk demonstrated a 1 year adverse event rate of 3.1%.19

timi
http://www.mdcalc.com/timi-risk-score-for-uanstemi/

Several flaws affect this decision aid. A score of 0 does not risk stratify below 1%, and a score of 0 is not common. 10% to 20% of patients were stratified as low risk based on scores 0-1.15-18  Aspirin use alone provides a score of 1. This decision aid was not derived for the undifferentiated chest pain population in the ED, but rather to determine which patients would benefit from early invasive therapy. Chase in 2005 evaluated TIMI in an ED population of undifferentiated chest pain patients.15  The cohort consisted of 1,458 patients, with 136 adverse events. Eight adverse events occurred over 30 days, or 1.2%, with mortality 0.2%. 15  Pollack et al. found a 2% MACE rate at 30 days with TIMI 0.16 Hess et al. found insufficient sensitivity with TIMI use in 17,265 patients.18 Unlike other decision aids and scores, the TIMI score does not stratify patients into discrete groups, and parts of the score are subjective, most importantly the presence of severe angina. The use of this score for risk stratification does not have appropriate characteristics to discharge patients from the ED.18,20,21

 Modified TIMI

The modified TIMI score was designed for ED use based on four variables: elevated cardiac biomarker, age > 65 years, ischemic ECG changes, and history of CAD. In one study of 947 patients with chest pain, the modified TIMI had similar predictive capability as the original TIMI. The same flaws exist with use of the modified score, as the MACE rate is 2.4% in the lowest risk category.22

Global Registry of Acute Coronary Events (GRACE) score

The Global Registry of Acute Coronary Events (GRACE) score, developed in 2003, is accurate in predicting in-hospital, 3 month, and 6 month mortality in ACS.20,21,23,24 The score relies on 8 variables from history, examination, ECG, and laboratory tests, each given a specific weighted score based on predictive value, shown below. It has been externally validated.22 Rates of adverse cardiac events significantly increase as the score rises, ranging from 0.2% for scores less than 60 to above 52% for scores greater than 250. Subsequent evaluations of the score have demonstrated that patients with scores ranging from 0-60 still have a 2.9% risk of adverse coronary event within 30 days.21,23,24 The score is difficult to use in the ED, it does not stratify patients into separate risk categories, and it was not designed to assess undifferentiated chest pain.20,21

grace
http://www.mdcalc.com/grace-acs-risk-and-mortality-calculator/

The Heart Score

The HEART score has gained popularity in recent years due to its ease of use, applicability, and multiple validations. Not only has the score demonstrated ability to stratify patients into low risk appropriate for discharge, but also those patients at high risk and need for possible intervention.21,25-28 It consists of several components, demonstrated below. The original score used Troponin > 2X normal limit, rather than 3X.  Patients with scores 0-3 are low risk (appropriate for discharge), 46 moderate risk (appropriate for admission/observation), and > 7 high risk (consideration of intervention). 21,25-28 The original derivation study utilized 122 patients in 2008, evaluating for the primary outcome of acute myocardial infarction (AMI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) and death plus a combined endpoint of AMI, PCI, CABG and death.26 Of low risk patients, 2.5% experienced an adverse coronary outcome.26 Of high risk patients, 72.7% experienced an adverse event. Following derivation, the score was externally validated.96 A study in 2010 found a rate of 0.99% in 303 low risk patients, with adverse events occurring in 65.2% of high risk patients.27 One study in 2013 found a 1.7% event rate in patients stratified to low risk, with 50.1% high risk patients experiencing adverse event. Use of this score dropped admissions by at least 20%, while maintaining negative predictive values of > 99% at 30 days.27,28 A recent JAMA publication found low risk HEART scores possess a 0.20 LR for ACS (95% CI, 0.13-0.30), while the patients categorized as high risk had a 13 LR (95% CI, 7.0-24) for ACS.29

HEART Score

Component Grading Score
History Highly suspicious

Moderately suspicious

Slightly or non-suspicious

2

1

0

ECG Significant ST-depressions

Nonspecific repolarization disturbance

Normal

2

1

0

Age > 65 years

45-64 years

< 45 years

2

1

0

Risk factors > 3 risk factors, or history of CAD

1-2 risk factors

No known risk factors

2

1

0

Troponin > 3X normal limit

> 1 – < 3X normal limit

< Normal limit

2

1

0

Several aspects of this score must be considered. The first involves troponin, as one elevated troponin with no other points provides a score of 2. Dynamic ECG changes with no other points provide a score of 2 as well. The third factor deals with risk factors, as the patient who has no past medical history on record may have undiagnosed hypertension, hyperlipidemia, or diabetes.

These scores have been compared in several studies. One investigation compared GRACE, TIMI, and HEART scores. In this study, 34% of the study with a TIMI 0-1 had a 2.8% rate of MACE at 6 weeks, 14% had a GRACE 0-60 with an adverse rate of 2.9%, and 36.4% had HEART 0-3 with adverse rate of 1.7%.30  Sun in 2015 compared TIMI and HEART scores; a HEART score 0-3 had a NPV 98.2% (95% CI: 0.978-0.986) and c-statistic of 0.753, while TIMI 0 had NPV of NPV 97.8%, 95% CI: 0.971-0.983) c-statistic 0.678.31 Sun recommended the HEART score, which has better discrimination and outperforms TIMI within low-risk categories.31 A review in 2011 comparing TIMI, GRACE, HEART, and PURSUIT scores recommended HEART due to its ease of use, greater ability to categorize patients, and greater accuracy in stratifying patients to low risk.21

Chest Pain Pathways

Accelerated diagnostic protocol (ADP) use has the potential to identify low risk chest pain patients appropriate for discharge. Several trials have utilized repeat troponin testing with TIMI. The ASPECT trial conducted in 2011 identified low risk patients defined by TIMI 0, ECG without new ischemic changes, and negative point of care biomarker at 0 hr and 2 hr.32 The primary outcome was major adverse cardiac event (MACE) within 30 days. Approximately 10% of patients were low risk, and of these 352 patients, 3 experienced MACE. This provided a sensitivity of 99.3% and NPV of 99.1%.32 The new improved ADP evaluated patients utilizing the ASPECT trial definition for low risk.33 Investigators compared this definition with a new edition based on modifications: troponin I at 0 hr and 2 hr, high sensitivity troponin T at 0 hr and 2 hr, and patients with a TIMI 1 and negative biomarkers.  Of the 1,000 patients, 123 were low risk (12.3%). Two of 123 patients experienced ACS at 30 days. All pathways demonstrated similar sensitivities except for the group with TIMI 1, where sensitivity was 97%. However, the amount of patients categorized as low risk reached 19.7%.33 The ADAPT trial in 2012 used normal ECG, TIMI score of 0, and two negative troponin I at 0 hr and 2 hr.34 This study consisted of 1,975 patients, of which 302 patients experienced MACE.  Of 392 patients meeting criteria for low risk, 1 patient experienced MACE, for a sensitivity of 99.7% (95% CI 98.1% to 99.9%) and NPV of 99.7% (95% CI 98.6% to 100.0%).34

Mahler et al. in 2015 attempted to validate the ADAPT trial in the U.S. using secondary analysis of 1,140 patients with TIMI 0-2, negative ECG for ischemia, and negative biomarkers.35 MACE occurred in 2.7% of the population, which is lower than prior studies. However, this use of the ADP in this trial identified 48.3% of the population for early discharge, with 0.9% of the patients experienced MACE within 30 days. Sensitivity for MACE was 83.9% in this study.35

Utilizing the HEART pathway can drop MACE to approximately 1% using the HEART score with 0 hr and 3 hr troponin testing.25,28  This pathway categorizes patients into separate categories based on HEART score. Those patients who are low risk undergo repeat troponin testing at 3 hr. If negative repeat troponin, the patient is appropriate for early discharge and encouraged to follow up with their primary physician. If the patient is moderate to high risk or has an elevated troponin above the 99th percentile threshold, the HEART Pathway recommends further evaluation (objective cardiac testing) in the hospital or observation unit (OU). The first study evaluating this pathway included 1,070 patients in an ED-based observation unit.25,28  The pathway demonstrated 100% sensitivity (95% CI 72% to 100%), with NPV 100% (95% CI 94.6% to 100%) for MACE, while identifying 82% of patients for discharge. Patients in this first cohort study did receive further testing.25,28   One validation study retrospectively investigated a multicenter cohort of 1,107 patients from 18 different U.S. EDs.25 Investigators found a sensitivity of 99% with NPV of 99%, while also identifying 20% of patients as low risk. Most importantly, no patients discharged home experienced MACE within 30 days.25A prospective validation was conducted of 282 patients, and investigators found decreased objective cardiac testing at 30 days by 12.1% (68.8% versus 56.7%; P=0.048) and length of stay by 12 hours (9.9 versus 21.9 hours; P=0.013), while increasing early discharges by 21.3% (39.7% versus 18.4%; P<0.001).36 In this prospective validation, no patients experienced MACE.36

HEART Pathway from Mahler 2015

A large component of the HEART pathway is utilizing a shared decision making model, which allows the patient to become an active participant in management decisions. This has been investigated in patients evaluated for pulmonary embolism and chest pain.37 Hess et al. in 2008 evaluated the use of a decision aid in chest pain, finding patients had significantly greater knowledge, greater engagement, and decided to be admitted less frequently to an observation unit for further testing.38 No major cardiac events occurred in the discharge group.38 By combining this with the HEART pathway’s MACE rate of < 1%, optimal NPV and sensitivity, and ability to categorize a significant proportion of undifferentiated chest pain as low risk, this pathway with shared decision making can decrease length of stay and decrease risk to the patient and provider.  If an institution decides to implement a CDR like the HEART score, a mechanism needs to be in place to insure outpatient follow up/studies as needed. 

Case Resolution: This patient’s HEART score is less than 3. His second troponin at 3 hr is negative. The patient agrees with the plan for discharge home and primary care follow up, as he feels comfortable with a risk of 1%.

Summary

– Risk stratification in patients with low risk chest pain has significantly evolved over the past decade. Multiple tools have been derived and evaluated for patient disposition decisions.

– TIMI and GRACE are not sensitive enough to use in the undifferentiated patient in the ED with chest pain.

– Decision pathways using these scores should be used with caution, though patients with two negative biomarkers and negative ECG for ischemia are at low risk for MACE.

– The HEART score and pathway provide the best sensitivity and NPV capability, while classifying a large percentage of patients as low risk.

– By combining the use of this rule with shared decision making, this pathway provides safe, efficient care, protecting the patient and physician.

References/Further reading

  1. Owens PL, Barrett ML, Gibson TB, Andrews RM, Weinick RM, Mutter RL. Emergency department care in the United States: a profile of national data sources. Ann Emerg Med 2010; 56:150–65.
  2. Pope JH, Aufderheide TP, Ruthazer R, Woolard RH, Feldman JA, Beshansky JR, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 2000; 342:1163–70.
  3. Pines JM, Isserman JA, Szyld D, Dean AJ, McCusker CM, Hollander JE. The effect of physician risk tolerance and the presence of an observation unit on decision making for ED patients with chest pain. Am J Emerg Med 2010; 28:771–9.
  4. Fleischmann KE, Goldman L, Johnson PA, et al. Critical pathways for patients with acute chest pain at low risk. J Thromb Thrombolysis 2002; 13:89–96.
  5. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics–2011 update: a report from the American Heart Association. Circulation 2011; 123:e18–e209.
  6. Amsterdam EA, Kirk JD, Bluemke DA, et al; American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology, Council on Cardiovascular Nursing, and Interdisciplinary Council on Quality of Care and Outcomes Research. Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association. Circulation 2010;122(17):1756-1776.
  7. McCarthy BD, Beshansky JR, D’Agostino RB, et al. Missed diagnoses of acute myocardial infarction in the emergency department: results from a multicenter study. Ann Emerg Med 1993;22(3):579–82.
  8. Freas GC. Medicolegal aspects of acute myocardial infarction. Emerg Med Clin North Am 2001;19(2):511–21.
  9. Rusnak RA, Stair TO, Hansen K, Fastow JS. Litigation against the emergency physician: common features in cases of missed myocardial infarction. Ann Emerg Med 1989;18(10):1029–34.
  10. Mitchell AM, Garvey JL, Chandra A, et al. Prospective multicenter study of quantitative pretest probability assessment to exclude acute coronary syndrome for patients evaluated in emergency department chest pain units. Ann Emerg Med 2006;47:447.
  11. Goldman L, Cook EF, Johnson PA, Brand DA, Rouan GW, Lee TH. Prediction of the need for intensive care in patients who come to the emergency departments with acute chest pain. N Engl J Med 1996 Jun 6;334(23):1498-504.
  12. Weinstock MB, Weingart S, Orth F, VanFossen D, Kaide C, Anderson J, Newman DH. Risk for Clinically Relevant Adverse Cardiac Events in Patients With Chest Pain at Hospital Admission. JAMA Intern Med 2015 Jul;175(7):1207-12.
  13. Goldman L, Weinberg M, Weisberg M, Olshen R, Cook EF, Sargent RK, et al. A computer-derived protocol to aid in the diagnosis of emergency room patients with acute chest pain. N Engl J Med 1982 Sep 2;307(10):588-96.
  14. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, et. al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA 2000 Aug 16;284(7):835-42.
  15. Chase M, Robey JL, Zogby KE, et al. Prospective validation of the thrombolysis in myocardial infarction risk score in the emergency department chest pain population. Ann Emerg Med 2006;48(3):252–9.
  16. Pollack CV Jr, Sites FD, Shofer FS, et al. Application of the TIMI risk score for unstable angina and non-ST elevation acute coronary syndrome to an unselected emergency department chest pain population. Acad Emerg Med 2006;13(1):13–8.
  17. Campbell CF, Chang AM, Sease KL, et al. Combining thrombolysis in myocardial infarction risk score and clear-cut alternative diagnosis for chest pain risk stratification. Am J Emerg Med 2009;27(1):37–42.
  18. Hess EP, Thiruganasambandamoorthy V, Wells GA, et al. Diagnostic accuracy of clinical prediction rules to exclude acute coronary syndrome in the emergency department setting: a systematic review. CJEM 2008;10(4):373–82.
  19. Sanchis J, Bodi V, Nunez J, et al. New risk score for patients with acute chest pain, non-ST-segment deviation, and normal troponin concentrations: a comparison with the TIMI risk score. J Am Coll Cardiol 2005;46(3):443–9.
  20. Hess EP, Agarwal D, Chandra S, et al. Diagnostic accuracy of the TIMI risk score in patients with chest pain in the emergency department: a meta-analysis. CMAJ 2010;182(10):1039-1044.
  21. Backus B, Six A, Kelder J, Gibler W, Moll F, Doevendans P. Risk Scores for Patients with Chest Pain: Evaluation in the Emergency Department. Current Cardiology Reviews 2011;7(1):2-8.
  22. Jaffery Z, Hudson MP, Jacobsen G, et al. Modified thrombolysis in myocardial infarction (TIMI) risk score to risk stratify patients in the emergency department with possible acute coronary syndrome. J Thromb Thrombolysis 2007;24(2):137–144.
  23. Fox KA, Dabbous OH, Goldberg RJ, Pieper KS, Eagle KA, et al. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). BMJ 2006 Nov 25;333(7578):1091.
  24. Elbarouni B, Goodman SG, Yan RT, Welsh RC, Kornder JM, Deyoung JP, et al. Validation of the Global Registry of Acute Coronary Event (GRACE) risk score for in-hospital mortality in patients with acute coronary syndrome in Canada. Am Heart J 2009 Sep;158(3):392-9.
  25. Mahler SA, Miller CD, Hollander JE, Nagurney JT, Birkhahn R, Singer AJ, et al. Identifying patients for early discharge: performance of decision rules among patients with acute chest pain. Int J Cardiol 2013;168:795–802.
  26. Six AJ, Backus BE, Kelder JC. Chest pain in the emergency room: value of the HEART score. Neth Heart J 2008;16:191–6.
  27. Backus BE, Six AJ, Kelder JC, et al. Chest pain in the emergency room. A multicenter validation of the HEART score. Crit Pathw Cardiol 2010;9:164–9.
  28. Mahler SA, Hiestand BC, Goff DC Jr, Hoekstra JW, Miller CD. Can the HEART score safely reduce stress testing and cardiac imaging in patients at low risk for major adverse cardiac events? Crit Pathw Cardiol 2011;10:128–133.
  29. Fanaroff AC, Rymer JA, Goldstein SA, Simel DL, Newby L. Does This Patient With Chest Pain Have Acute Coronary Syndrome? The Rational Clinical Examination Systematic Review. JAMA 2015;314(18):1955-1965.
  30. Backus BE, Six AJ, Kelder JC, Bosschaert MA, Mast EG, Mosterd A, et al. A prospective validation of the HEART score for chest pain patients at the emergency department. Int J Cardiol 2013 Oct 3;168(3):2153-8.
  31. Sun BC, Laurie A, Fu R, Ferencik M, Shapiro M, Lindsell CJ, Diercks D, et al. Comparison of the HEART and TIMI Risk Scores for Suspected Acute Coronary Syndrome in the Emergency Department. Crit Pathw Cardiol 2016 Mar;15(1):1-5.
  32. Than M, Cullen L, Reid CM, et al. A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet 2011;377: 1077–1084.
  33. Aldous SJ, Richards MA, Cullen L, Troughton R, Than M. A new improved accelerated diagnostic protocol safely identifies low-risk patients with chest pain in the emergency department. Acad Emerg Med 2012 May;19(5):510-6.
  34. Than M, Cullen L, Aldous S, Parsonage WA, Reid CM, Greenslade J, Flaws D, et al. 2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial Journal of the American College of Cardiology 2012. 59(23):2091-2098.
  35. Mahler SA, Miller CD, Litt HI, et al. Performance of the 2-hour accelerated diagnostic protocol within the American College of Radiology Imaging Network PA 4005 cohort. Acad Emerg Med 2015;22:452–460.
  36. Mahler SA, Riley RF, Hiestand BC, Russell GB, Hoekstra JW, Lefebvre CW. The HEART Pathway randomized trial: identifying emergency department patients with acute chest pain for early discharge. Circ Cardiovasc Qual Outcomes 2015 Mar;8(2):195-203.
  37. Geyer BC, Xu M, Kabrhel C. Patient preferences for testing for pulmonary embolism in the ED using a shared decision-making model. Am J Emerg Med 2014 Mar;32(3):233-6.
  38. Hess EP, Knoedler MA, Shah ND, Kline JA, Breslin M, Branda ME, et al. The chest pain choice decision aid: a randomized trial. Circ Cardiovasc Qual Outcomes 2012 May;5(3):251-9.

Disclosure of Adverse Events and Medical Errors

Authors: Allison Moyes, MD (EM Resident Physician, University of Washington / Harborview Medical Center, Seattle, WA) and Amy E. Betz, MD (Clinical Assistant Professor, Harborview Medical Center, University of Washington Division of Emergency Medicine, Seattle, WA) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) & Justin Bright, MD (@JBright2021)

The Institute of Medicine’s 1999 report “To Err is Human: Building a Safer Health System” drew attention to medical errors and the need for improving quality and safety in medicine.1  Since then, a body of literature has emerged suggesting that transparency around adverse events and medical errors benefits both providers and patients.  However, the actual rate of disclosing medical errors has lagged behind popular support for the concept.2-5

Benefits of error disclosure

  1. Provides support for patients and enhances patient-provider communication.2, 6-8
  1. Improves institutional awareness of errors which might otherwise go unreported. Analyses of why errors occur can lead to system-wide improvements in quality and safety.5
  1. Open disclosure of medical errors may make lawsuits less likely.2-3,6
  • In 2001, the University of Michigan adopted a program of full disclosure, which also offers compensation to patients for medical errors. Retrospective reviews have demonstrated a reduction in claims and liability costs since the program began.9
  • Disclosure policies in other isolated institutions and insurance networks have yielded inconsistent results.10
  • Nondisclosure of errors has been shown to decrease patient satisfaction and increase the likelihood of seeking legal advice.8
  • The cumulative effect of error disclosure on legal claims remains difficult to determine and largely unclear.

The disclosure gap

Patients and providers agree that errors resulting in otherwise preventable adverse events should be disclosed; however, actual rates of disclosure remain variable.2-6

  • Patient surveys often indicate a desire for disclosure of errors wherein minimal or no harm occurs as well.7
  • Whether to disclose these “near misses” appears to be more controversial among physicians and may account for a portion of nondisclosure cases.7

pic1

Uncertainty over which errors need to be disclosed, and how much information to share, may negatively impact rates of error disclosure.2,4,5,7

  • Mixed messaging within institutions can compound provider uncertainty. Surveys of risk managers, for instance, demonstrate strong support for the disclosure of errors but less support for apologizing for errors.9
  • Reducing conflict over error disclosure within institutions, through broad institutional support and policies, appears to improve disclosure rates.5,7

Concern exists over the possible legal repercussions of disclosure.

  • Some states have adopted “apology laws” which prevent portions of disclosure from being used in lawsuits.2
  • The protection provided by those laws varies significantly between states, however, and many states remain without any legal protection.
  • The net effect of error disclosure on legal claims remains unclear.

Steps for the disclosure process

  1. Plan for the conversation
  • Attempt to determine whether an error occurred and whether the error had an adverse impact on the patient. It can be difficult to say whether an error resulted in an otherwise preventable adverse event immediately.  Do your best to assemble the facts through discussion with all of the involved personnel, and acknowledge ambiguity if it exists.
  • Consult risk management at your institution before disclosing an error. Consider talking with your department’s quality improvement team as well.
  • Plan your wording carefully. Be careful not to speculate or place blame.  An admission of regret can be distinct from an admission of liability.
  • Be aware of your own emotions and how they may impact communication. Patients often perceive rationalizations or defensiveness negatively.  Aim for accountability and empathy.
  1. Set up for optimal communication
  • Choose a quiet location with minimal distractions.
  • Silence your pager and phone.
  • Sit down.
  • Arrange for an interpreter, if needed.
  • Have the appropriate personnel present.
    • Essential physicians – don’t overcrowd the meeting.
    • Include a nurse manager or pharmacist if involved in the incident.
  1. Essential components of disclosure

Based on patient preference studies, disclosing an error should include the following core components.2-4,6-7

  1. An apology.
  2. An explicit statement that an error occurred.
  3. A factual description of what the error was, why it occurred, and its clinical implications.
  • Acknowledge that the outcome of an error may be ambiguous at the time of disclosure.
  • Discuss the possible repercussions and how the medical team will monitor for and manage adverse effects, and plan for subsequent conversations.
  1. An opportunity for the patient to relate his/her experience.
  2. A description of steps being taken to prevent recurrence of similar errors.

Summary

Benefits of error disclosure include enhanced patient-provider communication, opportunity for system-wide improvements in quality and safety, and possibly fewer lawsuits.  Patients and providers agree that errors resulting in otherwise preventable adverse events should be disclosed; however, actual rates of disclosure remain variable.  Approach the disclosure process with a few key steps in mind: 1. Plan for the conversation by assembling the facts and consulting with risk management ahead of time, 2. Set up for optimal communication, and 3. Include each of the core components in the discussion (see above).

References / Further Reading:

  1. Kohn LT, Corrigan J, Donaldson MS. To Err Is Human: Building a Safer Health System. Washington, D.C.: National Academy Press; 2000.
  2. Gallagher TH, Waterman AD, Ebers AG, Fraser VJ, Levinson W. Patients’ and physicians’ attitudes regarding the disclosure of medical errors. JAMA 2003;289(8):1001-7.
  3. Gallagher, TH, Studdert D, Levinson W. Disclosing harmful medical errors to patients.  New England Journal of Medicine 2007; 356(26): 2713-2719.
  4. Chamberlain CJ, Koniaris LG, Wu AW, Pawlik TM. Disclosure of “Nonharmful” Medical Errors and Other Events: Duty to Disclose. Arch Surg. 2012;147(3):282-286.
  5. King ES, Moyer DV, Couturie MJ, Gaughan JP, Shulkin DJ. Getting Doctors to Report Medical Errors: Project DISCLOSE.  The Joint Commission Journal on Quality and Patient Safety, Volume 32, Number 7, July 2006, pp. 382-392(11).
  6. “Teaching Module: Talking about harmful medical errors with patients”. Tough talk: a toolbox for medical https://depts.washington.edu/toolbox/errors.html.  Accessed: 06 March 2016.
  7. Fein S, Hilborne L, Kagawa-Singer M, et al. A Conceptual Model for Disclosure of Medical Errors. In: Henriksen K, Battles JB, Marks ES, et al., editors. Advances in Patient Safety: From Research to Implementation (Volume 2: Concepts and Methodology). Rockville (MD): Agency for Healthcare Research and Quality (US); 2005 Feb. Available from: http://www.ncbi.nlm.nih.gov/books/NBK20500/
  8. Mazor KM, Reed GW, Yood RA, Fischer MA, Baril J, Gurwitz JH. Disclosure of Medical Errors: What Factors Influence How Patients Respond? Journal of General Internal Medicine. 2006;21(7):704-710. doi:10.1111/j.1525-1497.2006.00465.
  9. Kachalia A, Kaufman SR, Boothman R, Anderson S, Welch K, Saint S, et al. Liability Claims and Costs Before and After Implementation of a Medical Error Disclosure Program. Ann Intern Med. 2010;153:213-221.
  10. Kachalia A, Shojania KG, Hofer TP, Piotrowski M, Saint S. Does full disclosure of medical errors affect malpractice liability? The jury is still out. Jt Comm J Qual Saf. 2003;29:503-11.
  11. Loren DJ, Garbutt J, Dunagan WC, Bommarito KM, Ebers AG, Levinson W, Waterman AD, Fraser VJ, Summy EA, Gallagher TH. Risk managers, physicians, and disclosure of harmful medical errors.  Jt Comm J Qual Patient Saf. 2010 Mar;36(3):101-8.

The Crashing Trauma Patient

Author: Bryant Allen, MD (@bryantkallen, Assistant Profess of Emergency Medicine, Carolinas Medical Center) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) & Justin Bright, MD (@JBright2021, Senior Staff Physician, Henry Ford Hospital)

ABCDE: General principles for the resuscitation and treatment of the unstable trauma patient

Case 1: A 35-year-old male presents after a high-speed motor vehicle collision. He was the restrained driver of a vehicle traveling approximately 70 mph when it struck a tractor-trailer stopped in the roadway. First responders found him slumped in his seat, airbags deployed, with the seat fractured from the vehicle. The car had severe front-end damage. He was placed in a cervical collar by EMS and after a prolonged extraction was placed on a spine board. Obvious injuries included an open deformity to his right femur, a tender and distended abdomen, and multiple facial and scalp injuries. Vital signs per EMS included a maximum heart rate of 139 bpm, lowest blood pressure of 84/40 mmHg, respiratory rate of 30 bpm, and GCS of 6.

Introduction

Accidental and traumatic injuries remain one of the leading causes of death worldwide, accounting for 5.8 million deaths annually and a large percentage of ED evaluations.1 Increasing disease severity creates an environment that makes patient care difficult. The American College of Surgeons has created a protocol driven framework, Advanced Trauma Life Support, in order to overcome this challenge and achieve success in the “Golden Hour”.

Management of the crashing trauma patient can be hectic and challenging. The primary role of the traumatologist is to create a calm environment in the trauma bay in order to effectively designate roles and provide cohesive, structured care. Preparing the trauma team prior to arrival can be helpful in order to obtain appropriate equipment, including an airway cart, RSI drugs, tube thoracostomy, ED thoracotomy tray, or a Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) catheter. Managing the room and all members of the trauma team can be difficult, but can often make a sloppy and potentially unsuccessful resuscitation more organized. As the Boy Scouts of America motto states, “Be prepared.”

After preparation for the resuscitation is complete, initial evaluation and management of the unstable trauma patient can be framed using the ATLS Primary Survey mnemonic ABCDE.

A – Airway maintenance and cervical spine precaution

Cervical spine precautions

Patients presenting with debilitating traumatic injury have been found to have a high prevalence of cervical spine injuries, with between 4-34% of polytrauma patients suffering from cervical spine injury.2 Given this high likelihood of injury, care should be taken with initial evaluation, transport and bed transfer of these patients, with use of appropriately sized and fitted cervical collars. Manual in-line stabilization methods during intubation are important as well, given stabilization with a cervical collar during intubation can limit jaw movement, increasing the difficulty of intubation.2 However, when such interventions limit laryngoscopic views, as has been seen in the setting of direct laryngoscope usage, relaxation of aggressive immobilization may be necessary to facilitate successful intubation.3 Efforts to limit flexion and extension, including usage of a supraglottic airway, gum-elastic bougie or video laryngoscopy, should be considered for every polytrauma patient requiring airway management.

Intubation

In many cases, the unstable and crashing trauma patient will require securement of the airway through intubation. An extensive deep dive into this topic was covered recently (here). The trauma airway is an inherently difficult airway and should never be taken for granted. Patients present un-fasted and with pathology that often makes standard intubation approaches impossible. Additionally, they present with pathology that suffers greatly from even small periods of hypotension or hypoxia. As such, practitioners should have a well thought out airway management plan, with multiple backups and airway adjuvants available for immediate use at the bedside, including materials for a surgical airway.4

B – Breathing and ventilation

Pneumothorax

Traumatic pneumothorax may quickly develop tension physiology, resulting in devastating preload elimination, hypotension and hypoxia. As such, rapid identification and reversal are key to preventing decompensation or cardiac arrest. Several methods for decompression of pneumothorax are described. Needle decompression has been described and is still taught as part of ATLS; however, this method is often unsuccessful and has frequent complications, requiring the provider to be prepped for rapid conversion to finger thoracostomy.5 Recent literature has identified lack of appropriate placement of needle for decompression and inadequate angiocatheter length as potential causes of needle decompression failure.6 Given the timely need for reversal of tension physiology in the unstable trauma patient, efforts should be directed instead at performance of finger thoracostomy, a procedure used in the initial stages of tube thoracostomy placement.7  As resuscitation proceeds, immediate placement of a chest tube is reasonable over finger thoracostomy.

Several methods may be used to rapidly identify a pneumothorax, including X-ray, point-of-care ultrasound and auscultation of breath sounds. In the unstable trauma patient, auscultation of lung sounds can be extremely difficult with standard stethoscopes.8 Other components of the physical exam may point toward pneumothorax with tension physiology, such as tracheal deviation, subcutaneous emphysema with crepitus, and penetrating trauma. Supine radiographs of the chest certainly demonstrate large pneumothoraces, but there is growing literature to support improved identification of this pathology and other lung pathology with ultrasound.9-11 Examination of the intercostal spaces on the anterior chest wall with linear array probe may illustrate lack of lung sliding as evidence of pneumothorax, and in the setting of traumatic instability, should be acted upon.

In setting of rapid decompensation and pending cardiac arrest, many algorithms recommend immediate bilateral decompression in blunt, and ipsilateral decompression in penetrating trauma.5,12 Vigilance should be maintained in the post-intubation patient, given the propensity for worsening pneumothorax in the setting of positive-pressure ventilation.

C – Circulation with hemorrhage control

Hemorrhage identification and control

The most common etiology of hemodynamic collapse in the trauma patient is hemorrhagic shock. Given this, the trauma practitioner should quickly identify the shock state and determine the source of hemorrhage. ATLS teaches practitioners to look to “blood on the floor and then four more (chest, abdomen, pelvis/retroperitoneum, long bones)” as sources for major blood loss.

Superficial injuries

Blood from superficial and deep lacerations is often the most obvious source for blood loss. Despite the frequent overestimation of blood lost at the scene of a trauma, large volume exsanguination can occur without correction. Direct pressure to venous and arterial bleeding is often sufficient to prevent additional blood loss, but care should be made not to overpad dressings. Big, bulky dressings can be less effective that those that provide direct, pointed pressure to the site of hemorrhage. In the setting of continued blood loss despite pressure, the practitioner should be prepared to ligate bleeding vessels, either though whip-stitching of the vessel or closure of the wound with sutures/staples to provide tamponade. The key to a successful trauma resuscitation is exposure; a missed scalp laceration can result in severe hemorrhage that would have been easily addressed if the patient was rolled and scalp explored.

Hemothorax

Large volume blood loss into the chest can result from both blunt and penetrating trauma, and can potentially result in tension physiology. After identification of hemopneumothorax in the unstable trauma patient, a chest tube should be placed on the affected side. ATLS recommends placement of large bore chest tubes in the setting of any traumatic hemothorax large enough to be identified on chest radiograph.1 Often hemothorax is secondary to a lung laceration or intercostal vessel injury, and decompression with placement of chest tube may be the definitive management, with patients often not requiring further intervention. However, should the patient have massive output (see below), further surgical intervention is necessary.

Indication for surgical intervention for hemothorax
>1,500cc immediate output
>200cc/hr output for 2-4 hours
Patient requires large volume transfusion

With large volume hemorrhage, early initiation of auto-transfusion of the patient’s own whole blood should be attempted. Patient’s with suspected diaphragmatic injury, concomitant gastric injury with violation into the thorax or associated chest malignancy are potential contraindications for autotransfusion.13 Commercially available devices can be used to ensure adequate filtration when used in-line with chest tube suction devices.

Intra-abdominal hemorrhage

Damage to intra-abdominal organs, both solid and hollow, can result in large volume blood loss without significant changes to the external appearance of the patient.1 Gross examination of the abdomen and review of the mechanism of injury can lend some information as to the presence of an abdominal injury. In the absence of obvious signs of injury, the addition of the Focused Assessment Sonography in Trauma (FAST) exam can help to identify presence of intra-abdominal free fluid suggestive of traumatic hemorrhage. Given the high sensitivity and specificity, FAST examination carries an EAST Level II recommendation as the initial study for identifying intra-abdominal free fluid. Diagnostic peritoneal lavage may also be employed to identify hemorrhage in this setting. Many algorithms exist for the use of these procedures in the unstable patient instead of CT imaging. Positive studies should result in immediate surgical intervention, unless a contraindication is present.

image1
EAST Algorithm for evaluating for intra-abdominal injury in the hemodynamically unstable trauma patient.

Pelvic fractures

The pelvis also serves as a large cavity for blood loss, with a substantial increase in volume in the setting of acute pelvic ring fractures. In one cadaveric study, fracture of the pelvis resulting in a pelvic diastasis of 5cm resulted in a 20% increase in pelvic volume, with a high association of venous injury.14 As a result, large volumes of blood can rapidly accumulate in the pelvis. Binding the pelvis, either with commercially-available devices or with an appropriately fitted sheet, has been found to decrease the volume of the pelvis, but has not been shown to have a statistically significant decrease in blood loss.15 Given the potential for decreasing pelvic volume and blood loss, placement of a temporary pelvic binder is recommended in the setting of a potential pelvic source of hemorrhage. In the patient who has no other identifiable source for hemorrhage, pelvic angiography is the EAST recommended intervention over surgical intervention.

Extremity

The compartments containing long bones can serve as a large vacuum for blood loss in the setting of acute fracture, in addition to blood lost externally in the setting of open fractures. One study illustrated an average blood loss of greater than 1,200cc in the setting of isolated femur fractures in adults.16 Rapid identification of and splinting of fractures can result in improved pain control and decreased blood loss.17 For most fracture related external hemorrhage, external direct pressure is sufficient to prevent additional hemorrhage. Some devices exist for rapid wound packing which may be of benefit in this patient population. However, in the setting of massive hemorrhage with suspected arterial source, placement of a tourniquet may be indicated. Tourniquet use has illustrated decreased hemorrhage rates and improved morbidity and mortality, even when placed by first responders in the out-of-hospital environment.18,19 If placing such devices, carefully document placement location and specific time of placement to prevent prolonged tourniquet times.

General hemorrhage

One intervention proven to decrease death from bleeding and all-cause mortality at 30-days is the early administration of an antifibrinolytic agent tranexamic acid.20 This medication has shown great success when administered in the first hour after injury, though it did illustrate a slight association with increased risk of bleeding death if administered after 3 hours post-injury.20 As such, this medication is recommended in the setting of transfusion-requiring severe traumatic injury and should be given early in the evaluation, potentially in the pre-hospital setting.21 Recommended dosing is 1g administered IV over 10 minutes, with additional infusion of 1g over 8 hours. For further details, go here:

http://www.emdocs.net/ed-crash-course-txa-matters/
http://www.emdocs.net/txa-use-trauma-update/

Anticoagulant reversal

Use of anticoagulants and antiplatelet agents complicate the management of traumatic hemorrhage.22 Often the hemodynamically stable patient will be unable to provide medication history, and additional data may be necessary to know of concomitant anticoagulant use. Elderly patients, patients with history or evidence of atrial fibrillation and those with history of CVA should be considered at risk for usage of either anticoagulant or antiplatelet agents. Point-of-care PT/INR may help if the patient is using warfarin, but will otherwise be of little help to the practitioner.

In the setting of anticoagulant use, efforts should be made to reverse the anticoagulated state in the setting of life-threatening hemorrhage. Use of these agents has an associated increased injury severity and mortality in elderly patients, so rapid reversal of their effects is paramount.23 Several protocols exist for reversal in the trauma patient, but consensus statements do not exist. With the addition of new reversal agents, more work should be done to create reversal protocols.

pic2

pic3
Sample reversal protocols for anticoagulant agents in traumatic, life-threatening hemorrhage.

The use of anti-platelet agents also creates an unfavorable environment for hemostasis. Some protocols call for the transfusion of platelets to reverse effects. In the hemodynamically unstable patient, platelets should be added as part of standardized massive transfusion protocols, making this intervention less important for the specific reversal of the anti-platelet agent.

Resuscitative Thoracotomy

A third subset of shock that may present in the unstable and crashing trauma patient is that of cardiogenic shock. In the setting of blunt traumatic injury, this may be related to direct cardiac contusion or free wall rupture, resulting in pericardial tamponade. In the penetrating trauma patient, this may also be due to cardiac injury resulting in pericardial tamponade. As discussed in a prior post on traumatic cardiac arrest, emergency department thoracotomy can be considered in certain situations for correction of potentially reversible causes. Pericardiocentesis, though temporizing, may only have short-lived effects, given the nature of injuries that lead to pericardial tamponade in the setting of trauma. As such, rapid transition to thoracotomy is recommended.

New therapies

REBOA: A relatively new therapy for the management of traumatic hemorrhage of the trunk and torso is the use of resuscitative endovascular balloon occlusion of the aorta (REBOA). A technique initially described in 1950s, REBOA has been used in multiple arenas related to hemorrhage, from abdominal aortic aneurysm rupture to post-partum hemorrhage.24 Through the strategic placement of a balloon catheter in various zones of the aorta, a provider can selectively prevent distal blood flow to sites of hemorrhage, hopefully temporizing the patient until more definitive management can be performed. Several protocols have been proposed for initiation of REBOA in the ED, with more facilities introducing REBOA programs.25 Despite expanding its use, one review of REBOA use illustrated no improvement in hemorrhage-related mortality.26 REBOA remains a viable option in the age of damage control resuscitation of the patient with massive traumatic torso hemorrhage, though more research is needed to identify the best populations for usage.

Resuscitation

After identifying the potential source of exsanguination, efforts should be directed at resuscitation. “Damage control resuscitation” protocols have been developed to reduce the dangers of the “lethal triad” of trauma: acidosis, hypothermia, and coagulopathy.27 Infusion of crystalloid in large volumes has been linked to worsening acidosis and hemodilution. After initial field resuscitation with crystalloid, the unstable patient should be transitioned to blood product. The Eastern Association for the Surgery of Trauma guidelines give Level I recommendation for the transfusion of packed red blood cells in the setting of trauma and hemodynamic compromise, with less emphasis placed on hemoglobin directed transfusion.28 Combat literature has shown that the ideal transfusion product would be whole blood, though this resource is not often held in supply. The PROMMTT study found that practitioners attempted to replicate whole blood in their transfusion patterns, approaching a 1:1:1 or 1:1:2 ratio of plasma to platelets to packed red blood cells. Further investigation into ideal transfusion ratios by the PROPPR trial showed similar outcomes with these ratios, but noted a slight improvement in achievement of hemostasis and 24-hour mortality related to exsanguination in the 1:1:1 group.29

Given that hemorrhage is the most common etiology of shock in the trauma patient, little emphasis should be placed on vasopressor agents. Blood product replacement remains the gold standard in management of traumatic hemorrhagic shock. An exception to this rule involves patients with traumatic spinal cord injuries presenting with hypotension secondary to neurogenic shock.30 While guidelines recommend aggressive reversal of hypotension with fluid resuscitation, there is no one specific vasopressor agent for additional support recommended.31 Norepinephrine, phenylephrine or dopamine are all mentioned as potential agents, though phenylephrine should be avoided in those patients presenting with simultaneous bradycardia secondary to neurogenic shock.32

D – Disability; neurologic status

GCS/neurologic examination

After initial assessment, efforts should be made to perform a neurologic examination and determine the Glasgow Coma Scale of the patient. In the unstable patient, efforts may often proceed quickly to rapid sequence intubation, which can prevent adequate neurologic examination. Though protection of the patient’s airway is paramount, a neurologic exam should be performed and short-acting paralytics should be considered for RSI if possible.

Spinal cord injuries

Spinal column and cord injuries may complicate the poly-traumatized patient, leading to further injury load and potential source for hemodynamic instability. Patients will often present in a cervical collar and on spinal immobilization boards, though recent review of the literature suggests that spinal motion restriction methods may be more beneficial than immobilization boards. Efforts to minimize spinal manipulation should be attempted, with knowledge that life-saving measures may limit the ability to do so. During initial resuscitation, some elements of the physical exam may suggest spinal cord injury: focal neurologic deficit, priapism, or shock refractory to standard transfusion methods. Careful attention should be made to prevent hypoxia and hypotension, which increase morbidity and mortality.

Intracranial hemorrhage (ICH) management

Traumatic intracranial injury can complicate the course of the poly-traumatized patient. Though CT examination may be performed after the patient reaches a more hemodynamically stable state, suspicion of severe ICH should remain high so that early intervention can occur. The practitioner should look for signs of expanding ICH: palpable skull crepitus/obvious skull fracture, signs of basilar skull fracture, scalp hematoma, and facial bone fractures. Additionally, patients with diminished GCS without obvious signs of head injury should be considered high risk for ICH.

Progressively worsening ICH and associated edema can quickly progress, resulting in herniation of intracranial contents. This is often heralded by a combination of vital sign changes and lateralizing physical exam findings. Cushing’s response is the combination of bradycardia and hypertension in the herniating patient. Additionally, a unilateral dilated and unreactive pupil may be observed. Hemodynamic instability due to severe ICH and herniation requires rapid intervention. Hypertonic saline or mannitol may be used in an effort to decrease intracranial pressure, though guidelines do not exist for preferential use. The practice of hyperventilation should be avoided, unless rapid surgical decompression is possible, given the associated cerebral vasoconstriction and decreased oxygen delivery. Neurosurgical consultants should be involved as early as possible. Please go here for further details: http://www.emdocs.net/icp-management-update/

E – Endpoints/Markers (ATLS uses “Exposure/environmental control” here)

The ultimate goal in the resuscitation of the unstable and crashing trauma patient is to preserve life and return the patient to a normal physiologic state. However, the severity of injury may require prolonged resuscitation and multiple interventions before an external sign of response is noted by the practitioner. Surrogate markers for injury severity are the serum lactate level and base deficit. Severely elevated base deficit has been linked to increased mortality and blood product requirements, while the rate at which the base deficit is corrected in the resuscitation is associated with improved survival.33-35 Base deficit may be slightly better than lactate at this prediction, but lactate has also shown utility.36 Both are recommended as markers of resuscitation response by the most recent EAST Guidelines. Hemoglobin measurement is known to be inherently flawed in the acutely hemorrhaging patient and should not be used as an initial risk stratifying tool or resuscitation goal. Aggressive efforts to improve oxygen delivery, through prevention of further hemorrhage, application of supplemental oxygen and transfusion of blood product may be linked to more rapid correction of these physiologic markers and improved outcomes.37

Ultimately, the crashing trauma patient may require definitive surgical intervention. The initial resuscitation should be aimed at rapid identification of potentially reversible causes of hemorrhage, protection of the airway, and aggressive resuscitation. If the facility does not have the potential for surgical intervention, then the patient should quickly be prepped for transfer. Intubation, placement of chest tubes, and fracture splinting can be performed quickly in most emergency departments; however, a “stay-and-play” approach to the trauma patient is often detrimental to the patient and transport should not be delayed if available.

Case Recap

35-year-old male presents after a high speed MVC. Patient unresponsive on scene, placed in cervical collar and on spinal board by EMS after prolonged extrication. 5 minutes prior to patient arrival, EMS alerts EM providers to current vital signs and mechanism of injury. Trauma surgery paged to ED, lead EM physician briefs nursing and support staff in trauma bay prior to arrival, assures adequate procedural supplies are present and alerts blood bank to likely massive transfusion protocol event. Airway setup prepped.

Primary Survey:

A: Airway intact and without obvious obstruction

B: Spontaneous but sonorous respirations, left chest wall crepitus with diminished lung sounds

C: Thready pulses in bilateral radial locations and left dorsalis pedis; absent pulse in right DP; large volume hemorrhage from posterior scalp wound; open right femur fracture with continued hemorrhage; distended abdomen

D: GCS 6 (Eye – 1, Verbal – 2, Motor – 3)

E: Cool to touch, worse in distal right lower extremity

Vitals: HR 139 bpm, BP 84/40 mmHg manual, RR 30 bpm, SpO2 78%

Patient identified as having multiple potential sources for shock on arrival. After initial assessment, he underwent endotracheal intubation using ketamine and rocuronium. Video laryngoscope was used primarily, and intubation was successful on first attempt with no worsening hypoxia. Lack of breath sounds with associated crepitus to the left chest wall raised concern for left hemopneumothorax, and a left chest tube was placed with return of air and 500cc blood immediately. An autotransfuser device was employed, and the massive transfusion protocol was initiated at 1:1:1 ratio with 1g TXA IV. Given an open deformity to the right femur, a tourniquet was requested, but after the patient was placed in a traction splint, hemorrhage ceased. The scalp laceration was stapled for rapid hemostasis. Chest radiograph confirmed appropriate ETT placement, chest tube placement with small residual hemothorax, and left sided rib fractures. Pelvic radiograph demonstrated a sacral fracture with associated anterior diastasis, resulting in the placement of a pelvic binder. FAST examination was performed, illustrating presence of anechoic fluid collection in Morison’s pouch and peri-splenic views. After interventions and blood product administration, vital signs were notable for persistent hypotension and minimal improvement in tachycardia, resulting in immediate transit to operating room for exploratory laparotomy.

Discharge problem list following 15-day hospitalization:

Right-sided subdural hematoma, status post surgical decompression
Right maxillary, frontal sinus fractures
Rib fractures (R 3-5, L 3-8)
Left hemopneumothorax
Liver laceration
Splenic laceration, status post splenectomy
Sacral fracture
Pelvic ring fracture
Right open femoral shaft fracture, status post ORIF

References / Further Reading

  1. ATLS Student Course Manual, 10th edition
  2. Aoi Y, Inagawa G, Hashimoto K, Tashima H, Tsuboi S, Takahata T, Nakamura K, Goto T. Airway scope laryngoscopy under manual inline stabilization and cervical collar immobilization: a crossover in vivo cinefluoroscopic study. J Trauma. 2011; 71(1): 32-6.
  3. Manoach S, Paladino L. Manual in-line stabilization for acute airway management of suspected cervical spine injury: historical review and current questions. Ann Emerg Med 2007; 50(3): 236-45.
  4. Stephens CT, Kahntroff S, Dutton RP. The success of emergency endotracheal intubation in trauma patients: a 10-year experience at a major adult trauma referral center. Anesth Analg. 2009 Sep;109(3):866-72.
  5. Leigh-Smith S. Tension pneumothorax – time for a re-think? Emerg Med J 2005; 22:8-16.
  6. Chang SJ, Ros SW, Kiefer DJ, Anderson WE, Rogers AT, Sing RF, Callaway DW. Evaluation of 8.0cm needle at the fourth anterior axillary line for needle chest decompression of tension pneumothorax. J Trauma Acute Care Surg 2014; 76(4):1029-34.
  7. Aylwin CJ, Brohl K, Davies GD, et al. Pre-hospital and in-hospital thoracostomy indications and complications. Ann R Coll Surg Engl 2008; 90:54-7.
  8. Gaydos S. Clinical auscultation in noisy environments. J Emerg Med. 2012; 43(3): 492-3.
  9. Zanobetti M, Poggioni C, Pini R. Can chest ultrasonography replace standard chest radiography for evaluation of acute dyspnea in the ED? Chest. 2011; 139(5):1140-7.
  10. Zhang M, Liu ZH, Yang JX, Gan JX, Xu SW, You XD, Jiang GY. Rapid detection of pneumothorax by ultrasonography in patients with multiple trauma. Crit Care. 2006; 10(4): R112.
  11. Tasci O, Hatipoglu ON, Cagli B, Ermis V. Sonography of the chest using linear-array versus sector transducers: Correlation with auscultation, chest radiography, and computed tomography. J Clin Ultrasound. 2016 Feb 11 [Epub ahead of print]
  12. Sherren PB, Reid C, Habig K, Burns BJ. Algorithm for the resuscitation of traumatic cardiac arrest patients in a physician-staffed helicopter emergency medical service. Crit Care 2013; 17(2): 308.
  13. Salhanick M, Corneille M, Higgins R, Olson J, Michalek J, Harrison C, Stewart R, Dent D. Autotransfusion of hemothorax blood in trauma patients: is it the same as fresh whole blood? Am J Surg 202(6):817-822, 2011
  14. Baque P, Trojani C, Delotte J, et al. Anatomical consequences of “open-book” pelvic ring disruption: a cadaver experimental study. Surg Radiol Anat. 2005;27:487–490.
  15. Sadri H, Nguyen-Tang T, Stern R, Hoffmeyer P, Peter R. Control of severe hemorrhage using C-clamp and arterial embolization in hemodynamically unstable patients with pelvic ring disruption. Arch Orthop Trauma Surg. 2005;125:443–447.
  16. Lieurance R; Benjamin JB; Rappaport WD. Blood loss and transfusion in patients with isolated femur fractures. J Orthop Trauma. 1992; 6(2):175-9.
  17. Wood SP, Vrahas M, Wedel SK. Femur fracture immobilization with traction splints in multisystem trauma patients. Prehosp Emerg Care, 2003 Apr–Jun; 7(2): 241–3.
  18. Kragh JF, Littrel ML, Jones JA, et al. Battle casualty survival with emergency tourniquet use to stop limb bleeding. J Emerg Med 2011;41:590-597.
  19. Callaway DW, Robertson J, Sztajnkrycer MD. Law enforcement-applied tourniquets: a case series of life-saving interventions. Prehosp Emerg Care. 2015 Apr-Jun;19(2):320-7.
  20. Roberts I, Shakur H, Coats T, et al. The CRASH-2 trial: a randomized controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess. 2013; 17(10).
  21. Napolitano J. et al. Tranexamic acid in trauma: how should we use it? J Trauma Acute Care Surg. 2013 Jun;74(6):1575-86.
  22. Pieracci FM, Eachempati SR, Shou J, Hydo LJ, Barie PS. Use of long-term anticoagulation is associated with traumatic intracranial hemorrhage and subsequent mortality in elderly patients hospitalized after falls: analysis of the New York State Administrative Database. J Trauma. 2007 Sep;63(3):519-24.
  23. Boltz MM, Podany AB, Hollenbeak CS, Armen SB. Injuries and outcomes associated with traumatic falls in the elderly population on oral anticoagulant therapy. Injury. 2015 Sep;46(9):1765-71.
  24. Stannard A, Eliason JL, Rasmussen TE. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) as an adjunct for hemorrhagic shock. J Trauma. 2011; 71(6): 1869-72.
  25. Biffl WL, Fox CJ, Moore EE. The role of REBOA in the control of exsanguinating torso hemorrhage. J Trauma Acute Care Surg. 2015; 78(5): 1054-8.
  26. Morrison JJ, Galgon RE, Jansen JO, Cannon JW, Rasmussen TE, Eliason JL. A systematic review of the use of resuscitative endovascular balloon occlusion of the aorta in the management of hemorrhage shock. J Trauma Acute Care Surg. 2016; 80(2): 324-34.
  27. http://www.ahcmedia.com/articles/135668-damage-control-resuscitation
  28. EAST Guidelines Napolitano LM, Kurek S, Luchette FA, et al. Red Blood Cell Transfusion in Adult Trauma and Critical Care. J Trauma. 2009; 67(6): 1439-42.
  29. Holcomb JB, Tilley BC, Baraniuk S, Fox EE, et al; PROPPR Study Group. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015 Feb 3;313(5):471-82.
  30. Atkinson PP, Atkinson JL. Spinal shock. Mayo Clin Proc. 1996 Apr;71(4):384-9.
  31. Stein DM, Roddy V, Marx J, Smith WS, Weingart SD. Emergency neurological life support: traumatic spine injury. Neurocrit Care. 2012 Sep;17 Suppl 1:S102-11.
  32. Wing PC, et al. Early Acute Management in Adults with Spinal Cord Injury. J Spinal Cord Med. 2008; 31(4): 403–479.
  33. Davis JW, Kaups KL, Parks SN: Base deficit is superior to pH in evaluating clearance of acidosis after traumatic shock. J Trauma 1998;44:114-118.
  34. Davis JW, Shackford SR, MacKersie RC, Hoyt DB: Base deficit as a guide to volume resuscitation. J Trauma 1988;28:1464-1467.
  35. Rixen D, Raum M, Bouillon B, et al: Base deficit development and its prognostic significance in posttrauma critical illness: an analysis by the trauma registry of the Deutsche Gesellschaft für unfallchirurgie. Shock 2001;15:83-89.
  36. Shoemaker WC, Appel P, Bland R: Use of physiologic monitoring to predict outcome and to assist in clinical decisions in critically ill postoperative patients. Am J Surg 1983;146:43-38.
  37. Abramson D, Scalea TM, Hitchcock R, Trooskin SZ, Henry SM, Greenspan J: Lactate clearance and survival following injury. J Trauma 1993;35:584-589.

Additional FOAMed resources:

https://www.east.org/education/practice-management-guidelines/
http://lifeinthefastlane.com/
http://blog.ercast.org/
http://emcrit.org/