Tag Archives: resuscitation

Sepsis Biomarkers: What’s New?

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

A 43-year-old female presents with cough, congestion, wheezing, fever, and myalgias. She has a history of hypertension and recurrent UTI. She tried to overcome her symptoms with acetaminophen and oral fluids, but her symptoms have worsened. Her vital signs include RR 23, HR 102, BP 102/63, T 101.2, and Saturation 94% on RA. She has right-sided crackles on exam and appears ill, with dry mucosa. You start one liter of LR, while ordering CBC, renal panel, lactate, urinalysis, and chest Xray. Her chest Xray and urinalysis are negative, but after 1L LR, she still appears ill. The lactate returns at 4.2, and you start IV antibiotics with concern for septic shock. Your medical student on shift asks about using procalcitonin to rule out a bacterial cause of sepsis. You know about lactate, but are there other markers you can use in sepsis?

Sepsis is common in the ED and a major cause of morbidity and mortality. The body’s response to an infectious source in sepsis often results in dysregulated immune response, and current diagnosis relies on physiologic criteria and suspicion for a source of infection with laboratory and imaging studies. The host response triggered by the infection can be measured using several biomarkers.1-4

Biomarkers are defined by laboratory assessments used to detect and characterize disease, and they may be used to improve clinical decision-making. Through the years, complete blood cell count (CBC), troponin, creatine kinase (CK), lactate, C-reactive protein (CRP), ESR, and myoglobin have been advocated as biomarkers for a long list of conditions. However, what do biomarkers offer in sepsis? Some argue these biomarkers lack sufficient sensitivity outside of history and exam, while others state these markers can drastically improve medical decision making. In sepsis, diagnosis may not be easy, and a reliable biomarker may be able to improve early diagnosis, risk stratification, assessment of resuscitation, and evaluation.4-8

The post will evaluate several key biomarkers including lactate, procalcitonin, troponin, and novel lab assessments.


Lactate can be used in sepsis for resuscitation and severity stratification. It is normally produced in tissues due to pyruvate and NADH metabolism. There are several causes of lactate elevation, and not all are due to shock. Excess beta activity, inflammatory mediators, and liver disease may increase lactate.8-13  The table below demonstrates types and sources of lactate production.

Type A Type B1

Associated with disease

Type B2

Drugs and Toxins

Type B3

Associated with inborn errors of metabolism

Tissue Hypoperfusion


Anaerobic muscular activity


Reduced tissue oxygen delivery







Thiamine deficiency




Hepatic or renal failure


Short bowel syndrome







Lactate-based dialysate fluid



Alcohols: Methanol, Ethylene Glycol







Anti-retroviral agents

Pyruvate carboxylase deficiency


Glucose-6-phosphatase deficiency


Fructose-1,6-bisphosphatase deficiencies


Oxidative phosphorylation enzyme defects


The Surviving Sepsis Campaign recommends lactate for screening.1 Point of care (POC) lactate can be used for this screen, with specificity of 82% for lactate > 2 mmol/L. However, POC lactate has sensitivity of 30-40%, thus physicians must consider the clinical picture and patient appearance.11-16 Arterial blood is not required for this screening, and a venous blood gas (VBG) is fast and easily obtainable. As long as analysis occurs within 15 minutes of sampling, no effect from tourniquet or room temperature is observed.16,17 Lactate is not as reliable if the sample is run over 30 minutes from the time the sample is obtained.


As lactate elevates, mortality increases. In patients with lactate greater than 2.1 mml/L, mortality approximates 14-16%. If lactate reaches 20 mmol/L, mortality approximates 40% or higher.20 Lactate is an independent marker for mortality, no matter the patient’s hemodynamic status. Lactate greater than 4 mmol/L meets criteria for septic shock, and levels greater than 2 mmol/L are associated with increased mortality and morbidity.1,21-26

What about cryptic shock?

Cryptic shock is defined by sepsis in the patient with normal vital signs. A patient who is hemodynamically stable but with elevated lactate is at increased risk for mortality, as end organ damage occurs soon after lactate production. Thus, lactate serves as an early marker for shock and provides valuable diagnostic information. 9,11,20,21

What to do with the intermediate lactate level…

Lactate > 4 is associated with high mortality, but intermediate levels are as well (2.0-3.9 mmol/L).1,20-26 In fact, levels in this range meets Centers for Medicare and Medicaid Services (CMS) criteria for severe sepsis following SSC guidelines.Importantly, mortality can reach 16.4% for patients in this range, and ¼ of these patients with an intermediate level progress to clinical shock.22 Lactate levels greater than 2 warrant close monitoring and aggressive treatment with IV fluids and antimicrobials. The table below provides recommendations based on lactate level.

Lactate Level CMS Measure Resuscitation Recommendation
< 2 mmol/L None Lactate levels may be negative in over half of patients with sepsis. Clinical gestalt takes precedence over markers.
2-4 mmol/L Severe Sepsis Resuscitation with intravenous fluids, antimicrobials and reassessment of lactate within 60 minutes.
> 4 mmol/L Septic Shock Aggressive resuscitation warranted regardless of vital signs.


Lactate clearance is an important target in sepsis resuscitation. Many target a clearance of 10%, as early lactate clearance is associated with improved outcomes. Arnold et al. found 10% clearance to strongly predict improved outcomes.28 Delayed or no clearance is associated with high mortality, some studies showing 60% mortality rates.28-21 Lactate can be substituted for ScvO2, which requires invasive, specialized equipment.4,28-31


Lactate does not always elevate in sepsis, as 45% of patients with vasopressor-dependent septic shock demonstrate a lactate level of 2.4 mmol/L.32 Hernandez et al. suggested 34% of patients with septic shock did not have elevated lactate, though patients with no lactate elevation had a mortality of 7.7%, while those with lactate elevation 42.9% mortality.33 Lactate should not be used in isolation for assessing presence of shock or as a marker for clinical improvement. Rather, other measures such as mental status, heart rate, urine output, blood pressure, and distal perfusion in combination with lactate is advised.5-7,11



A great deal of literature has evaluated procalcitonin, a calcitonin propeptide produced by the thyroid, GI tract, and lungs with bacterial infection. This biomarker is released in the setting of toxins and proinflammatory mediators, while viral infections inhibit PCT through interferon-gamma production. These levels increase by 3 hours and peak at 6-22 hours, and with infection resolution, levels fall by 50% per day.5-7,34-40 This biomarker can be specific for bacterial infection, decreases with infection control, and is not impaired in the setting of immunosuppressive states (such as steroid use or neutropenia). However, other states including surgery, paraneoplastic states, autoimmune diseases, prolonged shock states, chronic parasitic diseases (such as malaria), certain immunomodulatory medications, and major trauma can increase PCT levels.34-37

Antibiotic Stewardship

Most of the literature evaluating PCT has been published in ICU studies for lower respiratory tract infections (LRTI) and sepsis. The literature suggests algorithms guided by PCT may be able to reduce antibiotic exposure and treatment cost, though with little to no effect on outcomes.37-49

In COPD and bronchitis, it can be difficult to differentiate viral versus bacterial infection. PCT may hold promise in assisting in this differentiation. The ProResp trial randomized patients to two arms, one guided by PCT and the other not.40 If PCT levels were greater than 0.25 mcg/L, antibiotics were given. Ultimately, the group based on PCT demonstrated less antibiotic use (44% in the PCT group, versus 83%), but no difference in length of stay or mortality.40 The ProHOSP trial was a similar trial with the same cutoff. This trial found similar results to the ProResp trial.41


PCT may be useful in sepsis diagnosis, but ultimately, the clinical context and picture must be considered.43-47 Source of infection, illness severity, and likelihood of bacterial infection should take precedence over a lab marker such as PCT, which may not return while the patient is in the ED. If concerned for sepsis, antimicrobials and resuscitation should be started.

 PCT can identify culture positive sepsis and may help in prognostication. Bacterial load may also correlate with level of PCT.34-47 PCT levels of < 0.25 mcg/L indicate that bacterial infection is unlikely, with levels greater than 0.25-0.50 mcg/L indicating bacterial source.38,45-49 However, sensitivity in one meta-analysis was 77%, with specificity of 79%.45

The PRORATA trial evaluated ICU patients admitted with sepsis.48 In this trial, antibiotic use was guided by PCT levels of 0.5 mcg/L. Similar to the prior studies discussed, decreased antibiotic use was found, but the all-important patient mortality benefit was not found. This level of 0.5 mcg/L was recommended as the cutoff for bacterial sepsis diagnosis in a 2015 meta-analysis.49  The following table depicts the PCT levels used in two key studies.

ProHOSP and PRORATA trial PCT Use41,48

Antibiotic Use PCT Level
< 0.1 mcg/L 0.1-0.25 mcg/L 0.25-0.5mcg/L 0.5-1mcg/L > 1.0 mcg/L
ProHOSP antibiotic use (respiratory infection only) No No Yes Yes Yes
PRORATA antibiotic use (sepsis patients in ICU) No No No Yes Yes

Ultimately, PCT should not influence provider decision to diagnose, resuscitate, and manage patients with criteria for sepsis.50,51 This lab may assist ICU providers, specifically when to discontinue antimicrobial therapy. Levels of 0.5 mcg/L strongly suggest bacterial sepsis. Providers in the ICU may be able to trend PCT levels in regards to decision of when to discontinue antimicrobials.  If the clinical picture suggests bacterial source, severe local infection (osteomyelitis, endocarditis, etc.), patient hemodynamic instability, PCT greater than 0.5 mcg/L, or no change in PCT level while on therapy, antimicrobial therapy should continue.37-49


Yep, that’s right, troponin. Troponin is most commonly used to diagnose acute MI, with the AHA stating elevation above the 99th percentile in healthy population meets criteria for ACS.50,51 Troponin can also be used to risk stratify patients entered into the HEART pathway, and high sensitivity troponin can increase sensitivity.50-54 Cardiac troponin consists of two forms: I and T (these are regulatory proteins). Injury of cardiac tissue results in these proteins entering the bloodstream. However, troponin can elevate in multiple settings, shown below.55-59

Cardiac Causes Noncardiac Causes
Acute and Chronic Heart Failure

Acute Inflammatory Myocarditis Endocarditis/Pericarditis

Aortic Dissection

Aortic Valve Disease

Apical Ballooning Syndrome

Bradyarrhythmia, Heart Block

Intervention (endomyocardial biopsy, surgery)


Direct Myocardial Trauma

Hypertrophic Cardiomyopathy


Acute Noncardiac Critical Illness

Acute Pulmonary Edema

Acute PE

Cardiotoxic Drugs

Stroke, Subarachnoid hemorrhage

Chronic Obstructive Pulmonary Disease

Chronic renal failure

Extensive Burns

Infiltrative Disease (amyloidosis)

Rhabdomyolysis with Myocyte Necrosis


Severe Pulmonary Hypertension

Strenuous Exercise/Extreme Exertion

Risk Stratification

Troponin elevation is associated in worse patient outcomes, particularly mortality, as well as increased length of stay. In sepsis, anywhere from 36-85% of patients may demonstrate troponin elevation. 58-68  This elevation is associated with septic shock and mortality, with almost two times the risk of death.58-64,69 Troponin elevation may be due to several factors including demand ischemia, direct myocardial endotoxin damage, cytokine and oxygen free radical damage, and poor cardiac oxygen supply due to microcirculatory dysfunction. 57,60,61,63,65,69 LV diastolic and RV systolic dysfunction are also associated with increased troponin and mortality.64

Troponin elevation in sepsis allows for prognostication and predicts a patient who is sicker. Resuscitation is essential with elevated troponin in sepsis. However, troponin’s role in resuscitation, the assay used, and the cut-off level need to be determined. If an elevation occurs, an ECG should be obtained, along with bedside echo to evaluate for wall motion abnormalities. Sepsis cardiomyopathy can cause diffuse hypokinesis, but focal wall abnormalities require emergent cardiology consultation.56-61


Novel Biomarkers

Sepsis has a complex pathophysiology, which results in a multitude of biomarkers released. These biomarkers are currently under study, and we will discuss several here.5-8

Endothelial Markers

Sepsis results in endothelial changes, associated with modifications in hemostatic balance, change in microcirculation, leukocyte trafficking, vascular permeability, and inflammation.

Measuring this endothelial dysfunction may allow earlier diagnosis of sepsis, as well as prognostication. These include vascular cell adhesion molecule (VCAM-1), soluble intercellular adhesion molecule (ICAM-1), sE-selectin, plasminogen activator inhibitor (PAI-1), and soluble fms-like tyrosine kinase (sFlt-1).5-8,70-73

Proadrenomedullin (ProADM)

This is a precursor for adrenomedullin, a calcitonin peptide. It likely functions in a similar fashion as PCT in the setting of acute cytokine release with bacterial infection. This peptide works as a vasodilator, though it has immune modulating and metabolic effects as well, and it is elevated in renal failure, heart disease, and cancer. ProADM may be able to risk stratify patients with sepsis and pneumonia into different categories based on level.73-79

One study evaluated an algorithm utilizing CURB-65 and ProADM levels.79 CURB-65 is a validated prognostic score for community-acquired pneumonia that consists of BUN > 19 mg/dL (>7 mmol/L), respiratory rate > 30, systolic blood pressure < 90 mm Hg or diastolic blood pressure  < 60 mm Hg, and age > 65 years.80 The algorithm combining CURB-65 and ProADM did not change patient outcome, though it did decrease patient length of stay.79 This marker could assist in prognostication and early discharge, but further study in the ED is needed.

Acute-Phase Reactants

Cytokines are released in response to inflammation, especially sepsis. There are multiple markers including IL-6, IL-8, IL-10, sTREM01, suPAR, CD-64 index, Lipopolysaccharide-binding protein (LBP), ICAM-1, and pentraxins. The greater the elevation in these markers, the worse the prognosis. However, these require further study before regular use can be recommended.8,81

Cardiac Biomarkers

Commonly utilized for heart failure and coronary disease, NT-proBNP and BNP may be associated with worse outcomes in sepsis. Higher levels can predict longer hospital stay and mortality. Obtaining these biomarkers may help predict cardiac dysfunction in sepsis and the need for inotropic medications, though these require further study.67,82-86 Providers must remember that NT-proBNP and BNP lack specificity, as valvular heart disease, Afib, PE, COPD, and hyperthyroidism can elevated these markers, while obesity may decrease levels. 81-85


Key Points:

  • Biomarkers cannot replace the bedside clinician, but they may assist clinical decision making, risk stratification, and prognostication. Lactate has the best evidence in sepsis.
  • Lactate is useful for assessing severity, screening, and resuscitation. However, it is not always elevated in sepsis. Venous POC levels are recommended.
  • Procalcitonin is a marker of bacterial versus viral It is not associated with mortality benefit, but may reduce antibiotic usage. PCT requires further study in the ED.
  • Troponin can be elevated in many conditions and is associated with worse prognosis in sepsis. Sepsis cardiomyopathy is more common than many providers realize.
  • Biomarkers on the horizon include endothelial activators, acute-phase reactants, BNP/NT-proBNP, and proadrenomedullin.


References/Further Reading

  1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013;39:165–228.
  2. Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, Sevransky JE.
Long-term mortality and quality of life in sepsis: a systematic review. Crit Care Med 2010;38:1276–1283.
  3. Strehlow MC, Emond SD, Shapiro NI, et al. National study of emergency department visits for sepsis, 1992 to 2001. Ann Emerg Med 2006;48:326–31.
  4. 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.
  5. Clerico A and Plebani M. Biomarkers for sepsis: an unfinished journey. Clin Chem Lab Med 2013; 51(6): 1135–1138.
  6. Rivers EP, Jaehne AK, Nguyen HB, Papamatheakis DG, Singer D, Yang JJ, Brown S, Klausner H. Early biomarker activity in severe sepsis and septic shock and a contemporary review of immunotherapy trials: not a time to give up, but to give it earlier. Shock 2013 Feb;39(2):127-37.
  7. Schuetz P, Aujesky D, Mueller C, and Mueller B. Biomarker-guided personalised emergency medicine for all – hope for another hype? Swiss Med Wkly 2015;145:w14079.
  8. Di Somma S, Magrini L, Travaglino F, Lalle I, Fiotti N, Cervellin G, et al. Opinion paper on innovative approach of biomarkers for infectious diseases and sepsis management in the emergency department. Clin Chem Lab Med 2013;51:1167–75.
  9. Jones AE. Lactate Clearance for Assessing Response to Resuscitation in Severe Sepsis. Acad Emerg Med 2013 August;20(8): 844–847.
  10. Marik PE, Bellomo R. Lactate clearance as a target of therapy in sepsis: A flawed paradigm. OA Critical Care 2013 Mar 01;1(1):3.
  11. Puskarich MA. Emergency management of severe sepsis and septic shock. Curr Opin Crit Care 2012 Aug;18(4):295-300.
  12. Gibot S. On the origins of lactate during sepsis. Crit Care 2012 Sep 10;16(5):151.
  13. Anderson LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW. Etiology and therapeutic approach to elevated lactate. Mayo Clin Proc 2013 Oct; 88(10): 1127–1140.
  14. Shapiro NI, Howell MD, Talmor D, et al. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med 2005; 45:524–8.
  15. Trzeciak S, Dellinger R, Chansky ME, et al. Serum lactate as a predictor of mortality in patients with infection. Intensive Care Med 2007; 33:970–7.
  16. Singer AJ, Taylor M, Domingo A, Ghazipura S, Khorasonchi A, Thode HC Jr, Shapiro NI. Diagnostic characteristics of a clinical screening tool in combination with measuring bedside lactate level in emergency department patients with suspected sepsis. Acad Emerg Med 2014 Aug;21(8):853-7.
  17. Jones AE, Leonard MM, Hernandez-Nino J, and Kline JA. Determination of the Effect of In Vitro Time, Temperature, and Tourniquet Use on Whole Blood Venous Point-of-care Lactate Concentrations. Acad Emerg Med 2007;14:587–591.
  18. Adams BD, Bonzani TA, Hunter CJ. The anion gap does not accurately screen for lactic acidosis in emergency department patients. Emerg Med J 2006;23:179-82.
  19. Iberti TJ, Leibowitz AB, Papadakos PJ, Fischer EP. Low sensitivity of the anion gap as a screen to detect hyperlactatemia in critically ill patients. Crit Care Med 1990;18:275-7.
  20. Puskarich MA, Trzeciak S, Shapiro NI, Albers AB, Heffner AC, Kline JA, Jones AE. Whole blood lactate kinetics in patients undergoing quantitative resuscitation for severe sepsis and septic shock. Chest 2013 Jun;143(6):1548-53.
  21. Mikkelsen ME, Miltiades AN, Gaieski DF, Goyal M, Fuchs BD, Shah CV, Bellamy SL, Christie JD. Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit Care Med 2009 May;37(5):1670-7.
  22. Puskarich MA, Illich BM, Jones AE. Prognosis of emergency department patients with suspected infection and intermediate lactate levels: a systematic review. J Crit Care 2014;29:334-339.
  23. Nichol AD, Egi M, Pettila V, et al. Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study. Crit Care 2010;14:R25.
  24. Cady LD, Jr., Weil MH, Afifi AA, Michaels SF, Liu VY, Shubin H. Quantitation of severity of critical illness with special reference to blood lactate. Crit Care Med 1973;1:75-80.
  25. Mizock BA, Falk JL. Lactic acidosis in critical illness. Crit Care Med 1992;20:80-93.
  26. Bakker J, Gris P, Coffernils M, Kahn R, Vincent JL. Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg 1996; 171:221–6.
  27. Nguyen H, Rivers E, Knoblich B, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2004; 32:1637–42.
  28. Arnold RC, Shapiro NI, Jones AE, et al. Multi-center study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock 2009;32:36–9.
  29. Jansen TC, van Bommel J, Schoonderbeek FJ, et al. Early lactate-guided therapy in intensive care unit patients a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med 2010;182:752–61.
  30. Jones AE, Kline JA. Use of goal-directed therapy for severe sepsis and septic shock in academic emergency departments. Crit Care Med 2005;33:1888–9.
  31. Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 2010;303:739–46.
  32. Dugas AF, Mackenhauer J, Salciccioli JD, Cocchi MN, Gautam S, Donnino MW. Prevalence and characteristics of nonlactate and lactate expressors in septic shock. J Crit Care 2012 Aug;27(4):344-50.
  33. Hernandez G, Castro R, Romero C, de la Hoz C, Angulo D, Aranguiz I, Larrondo J, Bujes A, Bruhn A. Persistent sepsis-induced hypotension without hyperlactatemia: is it really septic shock? J Crit Care 2011 Aug;26(4):435.e9-14.
  34. Jin M and Khan AI. Procalcitonin: Uses in the Clinical Laboratory for the Diagnosis of Sepsis. Lab Medicine 2010 Mar;41(3):173-177.
  35. Pieralli F, Vannucchi V, Mancini A, Antonielli E, Luise F, et al. Procalcitonin Kinetics in the First 72 Hours Predicts 30- Day Mortality in Severely Ill Septic Patients Admitted to an Intermediate Care Unit. J Clin Med Res 2015;7(9):706-713.
  36. Assicot M, Gendrel D, Garsin H, et al. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993;341:515–518.
  37. Meisner M. Pathobiochemistry and clinical use of procalcitonin. Clin Chim Acta 2002;323:17–29.
  38. Muller F, Christ-Crain M, Bregenzer T, Krause M, Zimmerli W, Mueller B, et al. Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial. Chest 2010;138(1):121–9.
  39. Schuetz P, Suter-Widmer I, Chaudri A, Christ-Crain M, Zimmerli W, Mueller B, et al. Prognostic value of procalcitonin in community-acquired pneumonia. Eur Respir J 2011;37(2):384–92.
  40. Christ-Crain M, Muller B. Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators. Eur Respir J. 2007;30:556–573.
  41. Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, Neidert S, Fricker T, Blum C, Schild U, Regez K, Schoenenberger R, Henzen C, Bregenzer T, Hoess C, Krause M, Bucher HC, Zimmerli W, Mueller B; ProHOSP Study Group. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009 Sep 9;302(10):1059-66.
  42. Schuetz P, Muller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2012; 9: CD007498.
  43. Jensen J, et al. Procalcitonin as a Marker of Infection, Sepsis, and Response to Antibiotic Therapy. Crit Care Med 2006:34;2596-2602.
  44. Anand D, Das S, Bhargava S, Srivastava LM, Garg A, Tyagi N, Taneja S, Ray S. Procalcitonin as a rapid diagnostic biomarker to differentiate between culture-negative bacterial sepsis and systemic inflammatory response syndrome: a prospective, observational, cohort study. J Crit Care 2015 Feb;30(1):218.e7-12.
  45. Wacker C, Prkno A, Brunkhorst FM, et al. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis 2013;13:426-435.
  46. Schuetz P, Briel M, Mueller B. Clinical outcomes associated with procalcitonin algorithms to guide antibiotic therapy in respiratory tract infections. JAMA 2013;309(7):717–8.
  47. Freund Y, Delerme S, Goulet H, et al. Serum lactate and procalcitonin measurements in emergency room for the diagnosis and risk-stratification of patients with suspected infection. Biomarkers 2012;17:590-596.
  48. Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M, Bernard M, Pasquet B, Régnier B, Brun-Buisson C, Chastre J, Wolff M; PRORATA trial group. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010 Feb 6;375(9713):463-74.
  49. Hoeboer SH, Van der Geest PJ, Nieboer D, Groeneveld AB. The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis. Clin Microbiol Infect. 2015;21:474–481.
  50. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Joint ESC/ACCF/AHA/WHF Task Force for Universal Definition of Myocardial Infarction. Third universal definition of myocardial infarction. J Am Coll Cardiol 2012 Oct 16;60(16):1581-98.
  51. Newby LK, Jesse RL, Babb JD, et al. ACCF 2012 expert consensus document on practical clinical considerations in the interpretation of troponin elevations: a report of the American College of Cardiology Foundation task force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2012;60:2427–63.
  52. Mahler SA, Riley RF, Hiestand BC, Russel GB, Hoekstra JW, Lefebvre CW, et al. The HEART Pathway Randomized Trial Identifying Emergency Department Patients With Acute Chest Pain for Early Discharge. Circ Cardiovasc Qual Outcomes March 2015;8 (2):195 – 203.
  53. Thygesen K, Mair J, Giannitsis E, et al. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J 2012;33:2252–7.
  54. Reichlin T, Hochholzer W, Bassetti S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009;361: 858–67.
  55. Kelley, W. E., J. L. Januzzi, and R. H. Christenson. Increases of Cardiac Troponin in Conditions Other than Acute Coronary Syndrome and Heart Failure. Clinical Chemistry 2009;55(12):2098-112. Web.
  56. Korff, S. Differential Diagnosis of Elevated Troponins. Heart 2006;92(7):987-93.
  57. Court O, Kumar A, Parrillo JE, Kumar A. Clinical review: Myocardial depression in sepsis and septic shock. Crit Care 2002;6:500-508.
  58. Hamilton MA, Toner A, Cecconi M. Troponin in critically ill patients. Minerva Anestesiol 2012 Sep;78(9):1039-45.
  59. Patil H, Vaidya O, Bogart D. A review of causes and systemic approach to cardiac troponin elevation. Clin Cardiol 2011 Dec;34(12):723-8.
  60. Bouhemad B, Nicolas-Robin A, Arbelot C, et al: Acute left ventricular dilatation and shock-induced myocardial dysfunction. Crit Care Med 2009; 37:441–447.
  61. Wilhelm J, Hettwer S, Schuermann M, Bagger S, Gerhardt F, Mundt S, Muschik S, Zimmermann J, Amoury M, Ebelt H, Werdan K. Elevated troponin in septic patients in the emergency department: frequency, causes, and prognostic implications.Clin Res Cardiol 2014 Jul;103(7):561-7.
  1. Bessière F, Khenifer S, Dubourg J, Durieu I, Lega JC. Prognostic value of troponins in sepsis: a meta-analysis. Intensive Care Med 2013 Jul;39(7):1181-9.
  2. Sheyin O, Davies O, Duan W, Perez X. The prognostic significance of troponin elevation in patients with sepsis: a meta-analysis. Heart Lung 2015 Jan-Feb;44(1):75-81.
  3. Landesberg G, Jaffe AS, Gilon D, Levin PD, Goodman S, Abu-Baih A, Beeri R, Weissman C, Sprung CL, Landesberg A. Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation*. Crit Care Med 2014 Apr;42(4):790-800.
  4. Clemente G, Tuttolomondo A, Colomba D, Pecoraro R, Renda C, Della Corte V, Maida C, Simonetta I, Pinto A. When sepsis affects the heart: A case report and literature review. World J Clin Cases 2015 Aug 16;3(8):743-50.
  5. Klouche K, Pommet S, Amigues L, Bargnoux AS, Dupuy AM, Machado S, Serveaux-Delous M, Morena M, Jonquet O, Cristol JP. Plasma brain natriuretic peptide and troponin levels in severe sepsis and septic shock: relationships with systolic myocardial dysfunction and intensive care unit mortality. J Intensive Care Med 2014 Jul-Aug;29(4):229-37.
  6. Cheng H, Fan WZ, Wang SC, Liu ZH, Zang HL, Wang LZ, Liu HJ, Shen XH, Liang SQ. N-terminal pro-brain natriuretic peptide and cardiac troponin I for the prognostic utility in elderly patients with severe sepsis or septic shock in intensive care unit: A retrospective study. J Crit Care 2015 Jun;30(3):654.e9-14.
  7. Courtney D, Conway R, Kavanagh J, O’Riordan D, Silke B. High-sensitivity troponin as an outcome predictor in acute medical admissions. Postgrad Med J 2014 Jun;90(1064):311-6.
  8. de Groot B, Verdoorn RC, Lameijer J, van der Velden J. High-sensitivity cardiac troponin T is an independent predictor of inhospital mortality in emergency department patients with suspected infection: a prospective observational derivation study. Emerg Med J 2014 Nov;31(11):882-8.
  9. Skibsted S, Jones AE, Puksarich MA, Arnold R, Sherwin R, Trzeciak S, et al. Biomarkers of endothelial cell activation in early sepsis. Shock 2013 May; 39(5): 427–432.
  10. Hack CE, Zeerleder S. The endothelium in sepsis: source of and a target for inflammation. Crit Care Med 2001; 29:S21–7.
  11. Shapiro NI, Schuetz P, Yano K, et al. The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis. Critical Care 2010; 14:R182.
  12. Becker KL, Nylen ES, White JC, Muller B, Snider RH, Jr. Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab 2004;89(4):1512–25.
  13. Elsasser TH, Kahl S. Adrenomedullin has multiple roles in disease stress: development and remission of the inflammatory response. Microsc Res Tech 2002;57(2):120–9.
  14. Struck J, Tao C, Morgenthaler NG, Bergmann A. Identification of an Adrenomedullin precursor fragment in plasma of sepsis patients. Peptides 2004;25(8):1369–72.
  15. Christ-Crain M, Morgenthaler NG, Struck J, Harbarth S, Bergmann A, Muller B. Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study. Crit Care 2005;9(6):R816–24.
  16. Christ-Crain M, Morgenthaler NG, Stolz D, Muller C, Bingisser R, Harbarth S, et al. Pro-adrenomedullin to predict severity and outcome in community-acquired pneumonia [ISRCTN04176397]. Crit Care 2006;10(3):R96.
  17. Schuetz P, Wolbers M, Christ-Crain M, Thomann R, Falconnier C, Widmer I, et al. Prohormones for prediction of adverse medical outcome in community-acquired pneumonia and lower respiratory tract infections. Crit Care 2010;14(3) R106.
  18. Albrich WC, Dusemund F, Ruegger K, Christ-Crain M, Zimmerli W, Bregenzer T, et al. Enhancement of CURB65 score with proadrenomedullin (CURB65–A) for outcome prediction in lower respiratory tract infections: derivation of a clinical algorithm. BMC infectious diseases 2011;11:112.
  19. Lim WS, van der Eerden MM, Laing R, Boersma WG, Karalus N, Town GI, Lewis SA, Macfarlane JT. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 2003 May;58(5):377-82.
  20. Reinhart K, Bauer M, Riedemann NC, Hartog CS. New Approaches to Sepsis: Molecular Diagnostics and Biomarkers. Clin Microbiol Rev October 2012;25(4):609-634.
  21. Castillo JR, Zagler A, Carrillo-Jimenez R, Hennekens CH. Brain natriuretic peptide: a potential marker for mortality in septic shock. Int J Infect Dis 2004;8:271–4.
  22. Turner KL, Moore LJ, Todd SR, Sucher JF, Jones SA, McKinley BA, et al. Identification of cardiac dysfunction in sepsis with B-type 
natriuretic peptide. J Am Coll Surg 2011;213:139–46.
  23. Varpula M, Pulkki K, Karlsson S, Ruokonen E, Pettilä V; FINNSEPSIS Study Group. Predictive value of N-terminal pro-brain natriuretic peptide in severe sepsis and septic shock. Crit Care Med 2007;35:1277–83.
  24. Post F, Weilemann LS, Messow CM, Sinning C, Munzel T. B-type natriuretic peptide as a marker for sepsis-induced myocardial depression in intensive care patients. Crit Care Med Lab Med 2008;46:748–63.
  25. Hur M, Kim H, Lee S, Cristofano F, Magrini L, Marino R, Gori CS, Bongiovanni C, et al. Diagnostic and prognostic utilities of multimarkers approach using procalcitonin, B-type natriuretic peptide, and neutrophil gelatinase-associated lipocalin in critically ill patients with suspected sepsis. BMC Infect Dis 2014 Apr 24;14:224.

The Thromboelastogram (TEG®): A Five-Minute Primer for the Emergency Physician

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

It’s three o’clock in the morning on your fourth night shift in a row.  While mustering the courage to rescue your energy drink from the dank, dark depths of the staff mini-fridge, you hear a familiar page: “trauma team to the trauma room.”  As you walk towards the ambulance bay, the trauma surgeon approaches with information regarding the incoming transfer:

  • 17 year-old male – MVC versus pedestrian
  • Seen at OSH where CTs demonstrated: epidural hematoma, grade III liver laceration, grade II splenic laceration, open book pelvic fracture, and extraperitoneal bladder rupture
  • Patient underwent external pelvic fixation and transfusion of blood products (8U PRBCs, 8U FFP and 4U Plts)
  • Most recent VS: BP 136/89, HR 92, RR (intubated/ventilated):14, SpO2 99% (FiO2 70%)

Drawing your attention to a piece of paper in his hand, detailing what appear to be labs from the outside facility, the surgeon points to a colorful figure: “I’m very concerned about this”:


Scanning your mind for intelligent thought, you realize that it’s been some time since you’ve ordered a thromboelastogram (TEG), let alone interpreted one.

If you’re like this physician, take a few minutes to scan the following review – the quick and dirty on TEGs is coming your way.

Thromboelastography – What is it?

Developed in 1948 by Dr. Hellmut Harter, thromboelastography is a mechanism of assessing coagulation based upon the viscoelastic properties of whole blood.2-8  In contrast to traditional, static measurements of hemostasis (PT, aPTT, INR, fibrinogen level, and fibrin degradation products), thromboelastography allows for an assessment of near real-time, in-vivo clotting capacity, providing the interpreter information regarding the dynamics of clot development, stabilization, and dissolution.7  When utilized as a point-of-care assay, graphic interpretation of thromboelastography (the TEG), offers the opportunity for an expedited assessment of coagulopathies (thrombocytopenia, factor deficiency, heparin effect, hypofibrinogenemia, and hyperfibrinolysis).7,9,12,13

How is a TEG performed?

In order to perform a TEG, a citrated-sample of whole blood is placed into a heated sample cup with calcium chloride (to overcome the effects of the citrate), kaolin (a negatively charged molecule known to initiate the intrinsic pathway10), and phospholipids (required for optimal functioning of the extrinsic pathway11) (Figure 2).  As the sample cup oscillates in a limited arc, formation of clot results in the generation of rotational forces on a pin suspended from a torsion wire.  Forces translated to the torsion wire are then, in turn, transmitted to an electrical transducer, creating a characteristic waveform (Figure 3).



I’ve heard of the Rapid TEG (r-TEG), is there a Difference?

When performed by a trained laboratory specialist, an r-TEG may be completed within 15 minutes as compared to the average 30-45 minutes processing time for a standard TEG.4,5,14  In contrast to a TEG, whole blood samples for an r-TEG may be performed with citrated or non-citrated samples.4 Samples utilized for an r-TEG are combined with tissue factor (activating the extrinsic pathway), and kaolin (activating the intrinsic pathway as above) +/- calcium chloride as applicable.4

I’ve also heard of ROTEM, what is it?

Although utilizing the technique developed by Dr. Harter, rotational thromboelastometry (ROTEM) differs from traditional thromboelastography in its mechanical application.  Unlike traditional thromboelastography, which utilizes a sample cup rotating in a limited arc, ROTEM employs a static sample cup with an oscillating pin/wire transduction system.  By comparison, ROTEM is also a more complex diagnostic test as it requires a number of differing reagents.  A complete discussion of ROTEM is outside the scope of this review.  If interested in further reading, see:

Tanaka K, Bolliger D. Practical aspects of rotational thromboelastometry (ROTEM). Available from: https://www.scahq.org/sca3/events/2009/annual/syllabus/workshops/subs/wkshp6pdfs/ROTEM%20-%20Tanaka.doc.pdf

Haemoview Diagnostics. ROTEM analysis: thromboelastometry. Available from http://www.haemoview.com.au/rotem-analysis.html

Haemoview. The 5 ROTEM tests. Available from http://www.haemoview.com.au/uploads/2/5/4/9/25498232/the_5_rotem_tests.pdf

How Do I Interpret TEG and r-TEG Results?

Drs. Semon and Cheatham of the Orlando Regional Medical Center Department of Surgical Education generated an excellent quick reference chart:


*Note: TEG-ACT (rapid) – reported for r-TEG only.

A TEG-Guided Transfusion Strategy

In addressing TEG and r-TEG abnormalities, experts recommend the following3:


The Quick and Dirty: Pattern Recognition

Perhaps most useful for the ED physician is knowledge of qualitative TEG representations:


Some clarification on DIC Stage 1 and 2:

  • Stage 1: Fibrinolysis results in the degradation of fibrin, increasing fibrin degradation products (FDPs). Excess FDPs result in clot de-stabilization.1
  • Stage 2: The cycle of clot formation and breakdown results in platelet and clotting factor consumption.1

Why Might an Emergency Medicine Physician Want to Know about this Test?

Coagulation abnormalities in trauma patients have demonstrated a significant association with infection, multi-organ failure, and death.15-18 Given its ability to quickly detect hematologic pathology, the TEG is becoming a tool for the evaluation of transfusion requirements/coagulopathy post transfusion in this patient population.3,12,13

What does the literature say?

Cotton, et al., 20114:

  • Pilot study to evaluate the timeliness of r-TEG results, their correlation to conventional coagulation testing (CCT – PT, aPTT, INR, platelet count, fibrinogen), and the ability of r-TEG to predict early blood transfusion.
    • 272 patients meeting requirements for major trauma activation
    • Outcomes:
      • All r-TEG values available within 15 minutes vs. 48 minutes for CCTs
      • ACT, r-value, k-time correlated with PT, INR, PTT (r >0.70; p<0.001)
      • MA and a-angle correlated with platelet count (p<0.001, p<0.001)
      • Controlling for demographics and ED vitals: ACT>128 predicted massive transfusion (>10 U) in the first 6 hours of presentation and treatment

Bottom line – r-TEG results were available within minutes, results correlated with conventional coagulation test results, and were predictive of the requirement for early massive transfusion.

Holocomb, et al., 201219:

  • Study to evaluate the reliability of r-TEGs versus CCTs in predicting blood product transfusion
    • 1974 major trauma patients, median ISS 17 (25% meeting criteria for shock; 28% transfused, 6% died within 24 hours)
    • Outcomes
      • When controlling for age, injury mechanism, weighted-Revised Trauma Score, base excess and hemoglobin, ACT predicted RBC transfusion and a-angle predicted massive transfusion better than PT/aPTT or INR (p<0.001).
      • a-angle was superior to fibrinogen for predicting plasma transfusion, and MA was superior to platelet count for predicting platelet transfusion (p<0.001)

Bottom line – r-TEG was more accurate in the prediction of requirements for RBC, plasma, and platelet transfusions as compared to traditional CCTs.

Wikkelso A, et al., 201612:

  • Cochrane Review including 17 current RCTs (n=1493 participants)
    • Per the authors:
      • Low quality studies: numerous biases
      • Limited generalizability: majority of studies center on cardiac patients undergoing surgical intervention

Bottom line – There is growing evidence to suggest that the utilization of TEG and ROTEM reduce transfusion requirements and improve morbidity in patients with bleeding, but additional studies are required.

Back to Our Case

Why was the trauma surgeon concerned? If we interpret our TEG values:

  • R time 20.0 => well above the upper limit of normal (10.0 minutes) = significantly prolonged time for clot formation
  • K time 13.2 => normal: up to 10.0 = prolonged fibrin cross-linking
  • a-angle 16.5 => normal >53.0 = limited clot formation
  • MA 38 => normal platelet function >50 = limited platelet function

More importantly, one quick glance at our TEG and through pattern recognition, we known that aside from his significant traumatic injuries, the patient is in trouble. This waveform is characteristic of DIC Stage 2.

Key Pearls

  • A TEG can be used as a rapid assessment of thrombosis and fibrinolysis.
  • Although additional RCTs are needed, TEGs utilized in trauma patients have been demonstrated to reduce transfusion requirements (important when we consider TACO/TRALI, risk of DIC, and blood-borne pathogens).
  • If nothing else, take a few minutes to review the characteristic TEG waveforms – depending on your laboratory processing time, knowledge of above tracings could allow early identification of coagulopathy and immediate treatment.


References / Further Reading

  1. Williams. Haemscope Basic Clinician Training: Fibrinolysis and Hyperfibrinolysis TEG Analysis. Available from: www.medicine.wisc.edu/~williams/TEG5_analysis.ppt
  2. Walsh M, Thomas S, Howard J, Evans E, Guyer K, et al. Blood component therapy in trauma guided with the utilization of the perfusionist and thromboelastography. J Extra Corpor Technol. 2001; 43(4):162-167.
  3. Semon G, Cheatham M. Thromboelastography in Trauma. Surgical Critical Care Evidence-Based Guidelines Committee. 2014. Available from: www.surgicalcriticalcare.net/Guidelines/TEG%202014.pdf
  4. Cotton B, Faz G, Hatch Q, Radwan Z, Podbielski J, et al. Rapid thromboelastography delivers real-time results that predict transfusion within 1 hour of admission. J Trauma. 2011; 71:407-417.
  5. Teodoro da Luz L, Nascimento B, Rizoli S. Thromboelastography (TEG): practical considerations on its clinical use in trauma resuscitation. Scand J Trauma Resusc Emerg Med. 2013; 21:29.
  6. Bollinger D, Seeberg M, Tanaka K. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transfus Med Rev. 2012: 26(1): 1-13.
  7. Thakur M, Ahmed A. A review of thromboelastography. Int J periop Ultrasound Apply Technol. 2012; 1(1):25-29.
  8. Nickson C. Critical Care Compendium: Thromboelastogram (TEG). 2014. Available from http://lifeinthefastlane.com/ccc/thromboelastogram-teg/
  9. Kashuk J, Moore E, Sawyer M, Wolhauer M, Pezold M, et al. Primary fibrinolysis is integral in the pathogenesis of acute coagulopathy of trauma. Ann Surg. 2010; 252: 434-444.
  10. Zhu S, Diamond S. Contact activation of blood coagulation on a defined kaolin/collagen surface in microfluidic assay. Thromb Res. 2014; 134(6): 1335-1343.
  11. Heemskerk J, Bevers E, Lindhout T. Platelet activation and blood coagulation. Throm Haemost. 2002; 88(2):186-193.
  12. Wikkelso A, Wetterslev J, Moller A, Afshari A. Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemostatic treatment versus usual care in adults or children with bleeding (Review). Cochrane Database of Systematic Reviews. 2016; 8:1-149.
  13. Luddington R. Thromboelastography/thromboelastometry. Clin Lab Haematol. 2005; 27(2):81-90.
  14. Jeger V, Zimmerman H, Exadaktylos A. Can rapid TEG accelerate the search for coagulopathies in the patient with multiple injuries? J Trauma. 2009; 66:1253-1257.
  15. Niles S, McLaughlin D, Perkins J et al. Increased mortality associated with the early coagulopathy of trauma in combat casualties. J Trauma. 2008; 64:1459-1463.
  16. Brohi K, Sing J, Heron M. Coats T. Acute traumatic coagulopathy. J Trauma. 2003; 54:1127-1130.
  17. Cotton B, Gunter O, Isbell J, et al. Damage control hematology: the impact of a trauma exsanguination protocol on survival and blood product utilization. J Trauma. 2008; 64;1177-1182.
  18. Cohen J, Call M, Nelson M, et al. Clinical and mechanistic drivers of cute traumatic coagulopathy. J Trauma Acute Care Surg. 2013; 75:S40-47.
  19. Holocomb J, Minei K, Scerbo M, Radwan Z, Wade C, et al. Admission rapid thromboelastography can replace conventional coagulation tests in the emergency department: experience with 1974 consecutive trauma patients. Ann Surg. 2012

A Myth Revisited: Epinephrine for Cardiac Arrest

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

 You receive a radio call from an EMS unit. They are transporting a 61-year-old male who collapsed approximately 5 minutes ago. He is currently in ventricular fibrillation, and the EMS crew is actively doing compressions. They have obtained IV access, defibrillated the patient once, given 1mg epinephrine IV, and are actively bagging the patient. The patient arrives, and you take over the resuscitation. Your partner cleanly intubates the patient while chest compressions are ongoing. The patient receives another defibrillation, and compressions resume. Should the patient receive more epinephrine? What’s the evidence behind its use?

Sudden cardiac arrest accounts for over 450,000 deaths per year in the U.S., with 15% of total deaths due to arrest.1-4 Close to half are out-of-hospital, with poor survival rate (7-9%).1-5

A prior emdocs.net post evaluated epinephrine use in cardiac arrest. Please see this at: http://www.emdocs.net/epinephrine-cardiac-arrest/. Epinephrine is a staple of the AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Updated guidelines were released in 2015, building on a “Chain of Survival”: recognition and activation of emergency response system, immediate high-quality cardiopulmonary resuscitation (CPR), rapid defibrillation, basic and advanced emergency medical services, and advanced life support and post arrest care including advanced cardiac life support (ACLS) for out-of-hospital cardiac arrest (OHCA).7,8 ACLS is considered the standard of care in cardiac arrest, though some argue a lack of evidence.

For more information on the updated guidelines, see http://eccguidelines.heart.org/wp-content/uploads/2015/10/2015-AHA-Guidelines-Highlights-English.pdf, https://emergencymedicinecases.com/acls-guidelines-2015-cardiac-arrest/, https://first10em.com/2015/10/21/acls-2015/, http://rebelem.com/rebel-cast-wee-our-top-5-aha-2015-guideline-updates-for-cpr-and-ecc/.

The Myth: Epinephrine improves patient survival and neurologic outcome in cardiac arrest.

Is this important?

A class IIb recommendation from the AHA states “standard dose epinephrine may be reasonable for patients with cardiac arrest” in the 2015 updates, with doses of 1mg of 1:10,000 epinephrine every 3-5 minutes intravenously.7 Epinephrine has alpha and beta adrenergic effects, which are thought to improve coronary perfusion pressure, though the effect on cerebral perfusion is controversial (and may worsen cerebral perfusion).

The recommendation for epinephrine is based on studies in the 1960s, which found epinephrine given to asphyxiated dogs improved survival.9 The alpha-adrenergic effects improved coronary perfusion in these dogs, with some benefit in survival.

If some is good, is more better? High dose epinephrine was assumed to be better, with several studies finding increased ROSC and survival to hospital admission, but no improvement in survival to hospital discharge or neurologic recovery.10-14 Studies suggest worse survival to hospital discharge and neurologic recovery with higher doses of epinephrine.7,15-20

What about standard dose epinephrine?  Studies suggest improvement in ROSC, but worse neurologic and survival to discharge. Why? The beta agonism provided by epinephrine increases myocardial work, increases tachydysrhythmias, promotes thrombogenesis and platelet activation, and reduces microvascular perfusion (including the brain).7,15

Now down to the nuts and bolts: the evidence on epinephrine…

Table 1 shows the studies on epinephrine. A study in 2011 evaluated over 600 patients with OHCA (one of the few randomized trials).16 Improved likelihood of ROSC, 24% in the epinephrine group versus 8%, with an odds ratio (OR) of 3.4 (95% CI 2.0-5.6) was found. Patients demonstrated no improvement in survival to hospital discharge.16 Ong et al. in 2007 found no difference in survival to discharge, survival to admission, or ROSC with epinephrine versus no epinephrine.17

Nakahara et al. conducted a retrospective study comparing epinephrine versus no epinephrine for patients with ventricular fibrillation, PEA, or asystole.18 Higher overall survival with epinephrine (17.0% vs 13.4%) was found, but not neurologically intact survival.18 Hagihara et al. conducted a prospective non-randomized analysis of over 400,000 patients and found an increase in ROSC with epinephrine (adjusted odds ratio 2.36), but no increase in survival or functional outcome.19 As discussed, ROSC occurred in the epinephrine group at higher rate (18.5% vs. 5.7%), but patients receiving epinephrine had lower survival at one month and worse neurologic outcome.19

One study found those with initially shockable rhythm demonstrated worse outcomes if they receive epinephrine for prehospital ROSC, survival at one month, and neurologic outcome at one month.20 A Swedish study found patients receiving epinephrine experience lower survival, with OR 0.30 (95% CI 0.07-0.82).21

How about BLS compared with ACLS?

ACLS measures include epinephrine, as compared with BLS focusing on optimizing compressions. Stiell et al. in 2004 analyzed 1,400 patients before use of ACLS measures, followed by 4,300 patients after ACLS was implemented.22 Admission rate increased by 3.7% (10.9% to 14.6%), but survival to discharge did not change.  Survivor neurologic status worsened after ACLS implementation (78.3% versus 66.8%).22  Olasveengen et al. evaluated ACLS with and without epinephrine, finding a 40% rate of ROSC in the group receiving epinephrine, versus 25% in the group receiving no epinephrine.23 Survival to discharge and neurologic outcomes were similar, though the epinephrine group had higher hospital admission rates.23  Sanghavi et al. compared BLS and ACLS in an observational cohort study.24 BLS patients had higher survival to hospital discharge (13.1% versus 9.2%), improved survival to 90 days, and better neurologic function.24

Table 1 – Studies evaluating epinephrine16-24

Study Outcome Odds Ratio (95% CI)
Holmberg et al. Survival decrease with epinephrine Survival 0.43 (0.27-.066) for shockable, 0.30 (0.07-0.82) for non-shockable rhythms
Stiell et al. Improved ROSC, no difference in survival to discharge Survival to discharge 1.1 (0.8-1.5)
Ong et al. No difference in ROSC or survival to discharge ROSC 0.9 (0.6-4.5), survival to discharge 1.7 (0.6-4.5)
Olasveengen et al. Improved ROSC, No difference in survival to discharge Survival to discharge 1.15 (0.69-1.91)
Jacobs et al. Improved ROSC, No difference in survival to discharge ROSC 3.4 (2.0-5.6), Survival to discharge 2.2 (0.7-6.3)
Hagihara et al. Improved ROSC, Worse survival and functional outcome ROSC 2.35 (2.22-2.5), Survival 0.46 (0.42-0.51), Functional outcome 0.31-0.32 (0.26-0.38)
Nakahara et al. No difference in neurologic outcome or total survival Neurologic outcome 1.01 (0.78-1.30) for shockable and 1.57 (1.04-2.37) for nonshockable rhythms; Total survival 1.34 (1.12-1.60) for shockable and 1.72 (1.45-2.05) for nonshockable rhythms
Sanghavi et al. No epinephrine associated with improved neurologic outcome, survival to discharge, and total survival Improved neurologic outcome 23.0 (18.6-27.4) for no epinephrine, Survival to discharge 4.0 (2.3-5.7) for no epinephrine, Total survival 2.6 (1.2-4.0) for no epinephrine

The Bottom Line: Epinephrine can increase ROSC, but it does not improve survival to hospital discharge or neurological improvement and may worsen these outcomes.

How does this change practice? Epinephrine is a significant component of the AHA guidelines, despite the controversial literature. A role may exist for epinephrine, though further study is required. Studies suggest three phases (electrical, circulatory, and metabolic) are present in cardiac arrest.25 The electrical phase needs rapid defibrillation and compressions.15,25 The circulatory phase (within 10 minutes of arrest) focuses on perfusion, where epinephrine may improve cardiac perfusion. Epinephrine during the final metabolic phase (greater than 10 minutes after arrest) can impair oxygen utilization, increase oxygen demand and ischemia, cause dysrhythmia, increase clotting, and increase lactate.15,25

The timing and total dose of epinephrine can impact patient outcome.7,15,25-27 A study by Dumas et al. suggests timing of first administration and total epinephrine given impacts survival (with less epinephrine given related to improved outcome).25 This study found that 17% of patients in the group receiving epinephrine demonstrated a good outcome defined by “favorable discharge outcome coded by Cerebral Performance Category,” compared to 63% not receiving epinephrine. However, in this study patients with a shockable rhythm, patients receiving 1mg epinephrine, and patients receiving epinephrine less than 9 minutes after arrest demonstrate the best outcomes, not impacted by the total time of resuscitation. Patients receiving late or multiple doses of epinephrine have decreased neurologic survival.25

Table 2 – Epinephrine Dosing Outcomes25

Treatment Adjusted OR (95% CI)
Time to Epinephrine Dose

< 9 min

10-15 min

16-22 min

> 22 min


0.54 (0.32-0.91)

0.33 (0.20-0.56)

0.23 (0.12-0.43)

0.17 (0.09-0.34)

Total Epinephrine Dose

1 mg

2-5 mg

> 5 mg


0.48 (0.27-0.84)

0.30 (0.20-0.47)

0.23 (0.14-0.37)

Epinephrine within 10 minutes of arrest may provide the most benefit. Koscik et al. found earlier provision of epinephrine improved ROSC, from 21.5% to 48.6% (OR 3.45).26 Nakahara et al. compared early epinephrine in OHCA (within 10 minutes of arrest), finding early epinephrine was associated with survival (OR 1.73, 95% CI 1.46-2.04) and improved neurologic outcome (OR 1.39, 95% CI 1.08-1.78).27 However, there is potential harm with epinephrine within the first two minutes of arrest.27 Anderson et al. compared epinephrine before or after the second defibrillation attempt.28 Patients receiving epinephrine before the second defibrillation demonstrated decreased survival (OR 0.70), decreased functional outcome (OR 0.69), and decreased ROSC (OR 0.71). This study suggests epinephrine within the first two minutes after arrest can be harmful, and they recommend epinephrine should be given after the second defibrillation.27

Some support targeting coronary perfusion pressure (CPP), or the aortic to right atrial pressure gradient during the relaxation phase of CPR. Targeting coronary perfusion pressure is supported by several animal studies.29,30 CPP levels > 15 mm Hg demonstrate greater likelihood of ROSC.31 Epinephrine is most commonly used to maintain CPP levels with compressions. However, this needs further study and requires the use of invasive monitoring.25,31

What improves outcomes?

Components that improve outcomes include witnessed arrest, witnessed by EMS, bystander CPR, shockable rhythm (VF/VT), early defibrillation, minimal interruptions to CPR, automated external AED use, and therapeutic hypothermia in comatose cardiac arrest patients.7,15,32 Optimal chest compressions and early defibrillation if warranted are essential.7 Emergency PCI is recommended for all patients with STEMI and for hemodynamically unstable patients without ST elevation infarction if a cardiovascular lesion is suspected. Targeted temperature management between 32oC and 36oC is acceptable for comatose patients with ROSC.7 The 2015 recommendations for BLS measures are shown below. 7,32

2015 Guideline Recommendations for Compressions
-Perform compressions at rate 100-120 per minute

-Perform compressions at depth of 5-6 cm (at least 2 inches), but not more than 6 cm (2.4 in)

-Rescuers should allow full chest wall recoil and avoid leaning on the chest between compressions

-Rescuers should minimize the frequency and duration of intervals between compressions

-Audiovisual devices and compression depth analyzers can be used to optimize CPR quality

Bottom Line: The most important aspect of care in cardiac arrest is basic life support measures with compressions and early defibrillation.



– 2015 AHA Guidelines state epinephrine is reasonable to give for patients in cardiac arrest.

– Recommendations are based on studies with asphyxiated dogs in the 1960s.

High dose epinephrine is harmful and is not advised.

– Epinephrine can increase ROSC, but it may worsen neurologic outcome and survival upon discharge.

– Epinephrine may provide the greatest benefit if given within 10 minutes of arrest (though it may be harmful if given before 2 minutes).

BLS measures with optimal compressions and early defibrillation are essential!


References / Further Reading

  1. Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation 2001; 104:2158.
  2. Rea TD, Pearce RM, Raghunathan TE, et al. Incidence of out-of-hospital cardiac arrest. Am J Cardiol 2004; 93:1455.
  3. Centers for Disease Control and Prevention (CDC). State-specific mortality from sudden cardiac death–United States, 1999. MMWR Morb Mortal Wkly Rep 2002; 51:123.
  4. Chugh SS, Jui J, Gunson K, et al. Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community. J Am Coll Cardio 2004;44:1268.
  5. Kuller LH. Sudden death–definition and epidemiologic considerations. Prog Cardiovasc Dis 1980; 23:1.
  6. Gillum RF. Sudden coronary death in the United States: 1980-1985. Circulation 1989; 79:756.
  7. Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132:S444-S464.
  8. Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122(Suppl 3):S729-67.
  9. Callaham M. Evidence in support of a back-to-basics approach in out-of-hospital cardiopulmonary resuscitation vs. “advanced treatment.” JAMA Intern Med. 2015;175:205-206.
  10. Stiell IG, Hebert PC, Weitzman BN, et al. High-dose epinephrine in adult cardiac arrest. N Engl J Med. 1992;327:1045-1050.
  11. Brown CG, Martin DR, Pepe PE, et al. A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group. N Engl J Med. 1992;327:1051-1055.
  12. Rivers EP, Wortsman J, Rady MY, et al. The effect of total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresuscitation period. Chest. 1994;106:1499-1507.
  13. Behringer W, Kittler H, Sterz F, et al. Cumulative epinephrine dose during cardiopulmonary resuscitation and neurologic outcome. Ann Intern Med. 1998;129:450-456.
  14. Guegniaud PY, Mols P, Goldstein P, et al. A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. N Engl J Med. 1998;339:1595-1601.
  15. Callaway CW. Questioning the use of epinephrine to treat cardiac arrest. JAMA. 2012;307:1198-1199.
  16. Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial. Resuscitation. 2011 Sep;82(9):1138-43.
  17. Ong ME, Tan EH, Ng FS, Panchalingham A, Lim SH, Manning PG, et al. Survival outcomes with the introduction of intravenous epinephrine in the management of out-of-hospital cardiac arrest. Ann Emerg Med. 2007 Dec;50(6):635-42.
  18. Nakahara S, Tomio J, Takahashi H, et al. Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study. The BMJ. 2013;347:f6829. doi:10.1136/bmj.f6829.
  19. Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, Miyazaki S. Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest. JAMA. 2012 Mar 21;307(11):1161-8. doi: 10.1001/jama.2012.294.
  20. Goto Y, Maeda T, Goto YN. Effects of prehospital epinephrine during out-of-hospital cardiac arrest with initial non-shockable rhythm: an observational cohort study. Critical Care. 2013;17(5):R188. doi:10.1186/cc12872.
  21. Holmberg M, Holmberg S, Herlitz J. Low chance of survival among patients requiring adrenaline (epinephrine) or intubation after out-of-hospital cardiac arrest in Sweden. Resuscitation. 2002 Jul;54(1):37-45.
  22. Stiell IG, Wells GA, Field B, Spaite DW, Nesbitt LP, De Maio VJ, Nichol G, Cousineau D, Blackburn J, Munkley D, Luinstra-Toohey L, Campeau T, Dagnone E, Lyver M; Ontario Prehospital Advanced Life Support Study Group. Advanced cardiac life support in out-of-hospital cardiac arrest. N Engl J Med. 2004 Aug 12;351(7):647-56.
  23. Olasveengen TM, Sunde K, Brunborg C, Thowsen J, Steen PA, Wik L. Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. JAMA. 2009 Nov 25;302(20):2222-9.
  24. Sanghavi P, Jena AB, Newhouse JP, Zaslavsky AM. Outcomes After Out-of-Hospital Cardiac Arrest Treated by Basic vs Advanced Life Support. JAMA Intern Med 2015;175(2):196-204.
  25. Dumas F, Bougouin W, Geri G, Lamhaut L, Bougle A, Daviaud F, et al. Is epinephrine during cardiac arrest associated with worse outcomes in resuscitated patients? J Am Coll Cardiol. 2014; 64(22):2360–7.
  26. Koscik C, Pinawin A, McGovern H, Allen D, Media DE, Ferguson T, Hopkins W, Sawyer KN, Boura J, Swor R. Rapid epinephrine administration improves early outcomes in out-of-hospital cardiac arrest. Resuscitation. 2013 Jul;84(7):915-20.
  27. Nakahara S, Tomio J, Nishida M, Morimura N, Ichikawa M, Sakamoto T. Association between timing of epinephrine administration and intact neurologic survival following out-of-hospital cardiac arrest in Japan: a population-based prospective observational study. Acad Emerg Med. 2012 Jul;19(7):782-92.
  28. Andersen LW, Kurth T, Chase M, et al. Early administration of epinephrine (adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: propensity score matched analysis. BMJ 2016; 353:i1577.
  29. Friess SH, Sutton RM, French B, et al. Hemodynamic Directed CPR Improves Cerebral Perfusion Pressure and Brain Tissue Oxygenation. Resuscitation. 2014;85(9):1298-1303.
  30. Sutton RM, Friess SH, Naim MY, et al. Patient-centric Blood Pressure–targeted Cardiopulmonary Resuscitation Improves Survival from Cardiac Arrest. American Journal of Respiratory and Critical Care Medicine. 2014;190(11):1255-1262.
  31. Paradis NA, Martin GB, Rivers EP, et al. Coronary Perfusion Pressure and the Return of Spontaneous Circulation in Human Cardiopulmonary Resuscitation. JAMA. 1990;263(8):1106-1113.
  32. Sasson C, Rogers MA, Dahl J, Kellermann AL. Predictors of survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2010 Jan;3(1):63-81.

FOAMed Resources Part VIII: EMS/Prehospital

Authors: Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC) and Manpreet Singh, MD (@MPrizzleER – emDOCs.net Associate Editor-in-Chief; Assistant Professor in Emergency Medicine / Department of Emergency Medicine – Harbor-UCLA Medical Center) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital)

The Prehospital environment is where emergency medicine begins. These providers are paramount in the initial stages of evaluation and management of critically ill patients. While most providers in the ED have medical or trauma rooms with adequate equipment and space, this is not the case for EMS. The stress, situation, and patient all present significant challenges to care providers.

The following list is comprised of blogs/podcasts with great education pearls, valid content, and major impact on EM, with clear reference citation. If you have found other great resources, please mention them in the comments below!


  1. https://prehospitalmed.com/tag/minh-le-cong/


Prehospital and Retrieval Medicine (PHARM) from Minh Le Cong is a fantastic prehospital resource with podcast and blog. Posts center on transport/retrieval medicine, airway, sedation, and prehospital critical care. This resource is a must for those with interest in airway, sedation, and EMS. Each podcast and blog post is well researched, providing succinct keys to success.


  1. http://emcrit.org/?s=prehospital


Scott Weingart’s blog and podcast contain several posts on cutting edge prehospital topics and procedures. REBOA, amputation care, hemostatic resuscitation, airway, sedation, hypothermia, and many more controversial topics are covered. These posts are well researched, with citations to the primary studies. Many of the prehospital podcasts contain interviews with experts in the field of prehospital medicine.


  1. http://www.fireemsblogs.com


Fire EMS Blogs is a network of sites covering EMS, rescue, hazmat, command, and training from San Diego. A wide variety of blogs are available including discussion of interesting cases, ECG interpretation, life as an EMS provider, and evidence-based medicine.


  1. http://hemscriticalcare.com


HEMS Critical Care from Philip Neuwirth brings together posts from blogs around the FOAMed universe pertaining to EMS/prehospital medicine into one place. If you’re interested in prehospital medicine and don’t have the time to regularly look through multiple online blogs, this resource does it for you.


  1. http://www.tamingthesru.com/hems-and-ems/


Taming the SRU is an all-around great resource concerning emergency medicine. The podcast and blog’s prehospital page covers topics including out-of-hospital cardiac arrest, stroke care, trauma, and STEMI. Posts and podcasts are thorough, and each podcast has a summary in bullet format.


  1. http://emfirstblog.com


EMFirst is dedicated to first responders and prehospital providers. Benjamin Ayd and Pratik Das cover classic and cutting edge EMS topics including TXA, REBOA, trauma, and ketamine. Not many posts are up now, but this site has a ton of potential.


  1. http://www.medicnerd.com


Medic Nerd from founder Mike Stewart seeks to provide enjoyable and effective EMS education through videos and blog posts. Videos explain physical exam findings, IV drip rates, prehospital procedures, interesting cases, and controversial studies. For those studying for a qualifying exam, flashcards are also provided (http://www.medicnerd.com/critical-care-paramedic-review-flashcards/).


  1. http://prehospitalwisdom.blogspot.com


Prehospital wisdom from Denver Paramedics is a blog with posts on EMS runs, interesting cases, and ECGs. Controversies in prehospital medicine are investigated, including C-spine protection, adenosine, distracting injury definition, and many others.


  1. http://resus.me/category/prehospital/


RESUS.ME has a complete prehospital section with EMS procedures, literature, and conferences. Posts provide key prehospital literature updates in a format that illuminates the key takeaways.


  1. http://www.ems12lead.com/


EMS 12-Lead is a leading resource for and by paramedics who are interested in all things EKG. Check out their posts to see EKG and cardiac rhythm analysis for patients in the field, and you can also submit your own case.


  1. http://www.scancrit.com


SCANCRIT is a blog covering anesthesia, critical care, and emergency medicine, with a focus on the critically ill patient. Posts are written by two Scandinavian anesthesiologists, who evaluate in-hospital and out-of-hospital medicine. Recent posts have investigated GCS, VF, hemorrhage evaluation and management, brain bleeds, and ATLS updates.

Thanks for reading our look at EMS resources. Comment below with other helpful sites!

Modern-Day Burn Resuscitation: Moving Beyond the Parkland Formula

Authors: Mary Ellen Billington, MD (EM Resident Physician, Parkland Memorial Hospital, Dallas, TX) and Brett D. Arnoldo, MD, FACS (Associate Professor, Department of Surgery, Parkland Memorial Hospital, Dallas, TX) // Edited by: Erica Simon, DO, MHA (@E_M_Simon) & Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital)

In the midst of a busy ED shift, a patient arrives by EMS. You immediately recognize the distinctive odor: a dry and unfortunately singed smell lingers in the air. As the catecholamines surge, you recognize your own tachycardia: it’s time to see a burn victim.

Thoughts race through your mind: What’s that  formula for fluid resuscitation? What rate do I use for the lactated ringers? What are the criteria that determine the need for burn center care? Where is my co-oximetry equipment?

Step away from your MDCalc – we’re going to calm that scorching stress-induced acid reflux with an update on the emergency department management of burns.

Mental Road Map

To adequately manage the burn victim, the emergency medicine physician must remember three key guidelines:

  1. The burn patient is a special type of trauma patient.
  2. The burn patient may be a toxicological patient.
  3. The burn patient requires comprehensive evaluation and management, and is best served by transferring to a burn center in accordance with ABA (American Burn Association) guidelines.

The Burn Patient is a Special Type of Trauma Patient

Begin with the ABCs: Is the airway intact? Is there concern that the airway may be lost? What is the patient’s projected course?

  • If the airway is not protected: intubate.
  • Signs of impending airway compromise include: stridor, wheezing, subjective dyspnea, and a hoarse voice.1
    • Severe burns to the lower face and neck may develop significant edema predisposing to airway obstruction.1
    • A history of the inhalation of superheated air, or steam in a confined space, is concerning for severe bronchial injury.1
    • Keep in mind that perioral burns and singed nasal hairs mandate an examination of the oropharynx for mucosal injury, however, these findings alone do not indicate airway involvement.2
    • Smoke inhalation victims may develop delayed respiratory failure: when in doubt, admit for observation and bronchoscopy.3
  • Projected Course: patients with burns involving >60% total body surface area (TBSA) tend to deteriorate rapidly: consider immediate intubation.1
  • Keep in mind that patients possessing burns involving a lower percentage of TBSA (e.g. < 40%), may require intubation if significant volume resuscitation is required.1
  • If the airway is intact, and the history and physical are not consistent with inhalational injury, it is prudent to administer oxygen by nasal cannula or face mask.1

Aside from airway concerns, complete your primary and secondary surveys and treat life-threatening emergencies as appropriate:

  • Consider a cervical collar if the mechanism is appropriate (blast injuries), or when doubt surrounds the circumstances of the injury.
  • Remember that full-thickness burns to the chest wall may lead to mechanical restriction of ventilation: consider escharotomy.1,3
    • Note: It is advised that escharotomies be performed in cooperation with a burn surgeon.4

In terms of fluid resuscitation:2

  • Burns <15% TBSA generaly require only PO fluid resuscitation.
  • Obtain large bore PIV access: two sites recommended for burns >40% TBSA.
  • Despite popular belief, IV access may be obtained through burned skin; ensure that lines are  well secured.
  • Obtain IO access if unable to obtain IV access.
  • Central lines equipped with invasive monitoring devices may provide useful volume-status metrics to guide resuscitation.

The What, When, and How Much of Fluids

  • In order to determine the volume of fluid resuscitation required for a burn patient, the Rule of Nines for adults and the Lund and Browder chart for children should be utilized (Figures 1 and 2 below).1,2
  • Remember: do not include first degree burns in the calculation of % TBSA.2
  • The over-estimation of % TBSA may result in hypervolemia, predisposing to a number of dangerous conditions:4
    • abdominal compartment syndrome
    • extremity compartment syndrome(s)
    • intraocular compartment syndrome
    • pleural effusions
Figure 1. Rule of Nines (Reference 5)
Figure 1. Rule of Nines (Reference 5)
Figure 2. Lund & Browder Chart (Reference 5)
Figure 2. Lund & Browder Chart (Reference 5)

Fluid Formulas:

  • The Parkland (or Baxter) Formula is possibly the most well-known and widely utilized formula:
    • 4 mL x weight in kg x % TBSA (up to 50%) = total volume of lactated ringers (LR) required for resuscitation
      • Half of the total volume is administered over the first 8 hrs post injury; the remaining, over the following 16 hours.
    • It is important to note that this formula is not universally accepted. Current trends in burn management literature emphasize a clinical assessment of volume status as essential in guiding fluid administration.1,2 Early consultation with a burn center is advised.1,2
  • The Advanced Burn Life Support (ABLS) handbook recommends the following for fluid resuscitation:
    • 2-4mL x kg body weight x % TBSA burn = volume of LR required for adult resuscitation (formula adjusted to 3-4mL x kg body weight x % TBSA burn for pediatric patients).6
      • Half of the total resuscitation volume is given over the first 8 hours, with administration of the remaining half titrated to patient response (urine output of 0.5mL/kg/hr for adults and 1mL/kg/hr for children).6
  • Inhalation injuries most commonly increase fluid resuscitation requirements.2
  • All resuscitation measures should be guided by perfusion pressure and urine output:4
    • Target a MAP of 60 mmHg, and urine output of 0.5-1.0ml/kg/hr for adults and 1-1.5mL/kg/h for pediatric patients.
    • The placement of a radial or femoral catheter is advised.4
    • Heart rate, pulse pressure, capillary refill, and mental status should also be assessed when determining resuscitation adequacy.
    • Additional markers, i.e. – lactate, base deficit, intestinal mucosal pH, and pulmonary arterial catheters are of limited use, and demonstrate varied mortality benefit.

We saw that the Parkland Formula and ABLS handbook recommend the use of LR, but are there recommendations regarding the use of other fluids for burn resuscitation?

  • Generally crystalloid solutions should be infused during the initial 18-24 hrs of resuscitation.1,4
  • It is recommended that 5% dextrose be added to maintenance fluids for pediatric patients weighing < 20kg.1
  • Hypertonic solutions tend to decrease initial resuscitation volumes, but are associated with increased renal failure and death, and therefore should be avoided.2,4,8
  • Colloid administration is a topic of debate.
    • Extensive heterogeneity exists regarding the recommendation for albumin utilization:
      1. Previous studies assessing albumin delivery in burn resuscitation (the most recent >15 years ago) demonstrated no statistically significantly improvement in patient outcomes.3  Today, however, a number of burn experts argue the value of albumin administration in the post capillary leak time frame (>18-24 hours post injury)given it’s ability to decrease third spacing.Further large scale, randomized control trials are needed.3
    • Blood transfusion is considered immunosuppressive, and is associated with increased mortality in burn patients. Blood products should be withheld unless there is an apparent physiologic need.2,4

The Burn Patient May be a Toxicological Patient

 In the evaluation of a burn patient, be sure to obtain a thorough history from EMS or from the patient. Victims of enclosed-space fires may be exposed to toxic levels of carbon monoxide and cyanide:

Your patient is the victim of an apartment fire. He has what appears to be red-tinged skin in areas absent burn; he is neurologically depressed, and suddenly decompensates into cardiac arrest. What toxic exposure do you suspect? How do you confirm your diagnosis? How will you treat your patient?

  • Carbon monoxide (CO) poisoning may manifest with persistent neurologic symptoms or even as cardiac arrest. Despite the board-style vignette stated above, cherry-red skin is a neither sensitive nor specific finding.3
  • If you suspect CO poisoning, order a carboxyhemoglobin level.1 In a patient with CO poisoning, pulse oximetry readings will be falsely normal, and the PaO2 and % hemoglobin saturation on ABG will be unaffected.1
  • How do you use a carboxyhemoglobin level? Subtract the carboxyhemoglobin level from the pulse oximetry level to determine true oxygen saturation.
    • Interpreting levels:3
      • Non-smokers: up to 1% normal
      • Smokers: 4-6% common
      • Any reading >10% = concern for significant exposure
    • To treat the toxic exposure administer 100% O2. Hyperbaric oxygen may be also be considered.2

Your burn patient, despite initial resuscitative efforts, maintains a persistent lactic acidosis and develops S-T elevation on EKG. What toxic exposure do you suspect? How do you treat your patient? 

  • The spectrum of the clinical presentation of cyanide poisoning varies from mydriasis,  to tachypnea and central apnea, to hypotension, to loss of consciousness and seizures.1
  • If concerned for cyanide toxicity, initiate 100% O2 therapy and administer hydroxocobalamin, with consideration for sodium thiosulfate (slower mechanism of action).1 Note: The commercially available cyanokit contains hydroxycobalamin.
  • Be sure to rule out other etiologies of lactic acidosis: under-resuscitation, CO poisoning, or missed traumatic injury.2

Additional Resuscitative Therapies and Considerations for Transfer

 What other resuscitative treatments may be indicated? When should you transfer a burn patient to a designated burn center?

  • In the evaluation of a burn patient, screening laboratory studies are appropriate.
    • Consider: ABG and CXR; cardiac enzymes, and a carboxyhemoglobin level.1,3
  • Administer a tetanus vaccination in the emergency department if indicated.
  • Control pain and administer anxiolytics as required.
  • Monitor resuscitation: bedside ultrasound is useful in the assessment of intravascular volume. Place a foley catheter or perform suprapubic cystotomy to monitor urine output and reduce the risk of abdominal compartment syndrome.3
  • Avoid hypothermia: warm the resuscitation room, administer warm inspired air, apply warm blankets, infuse warmed fluids, and cover wounds with clean dry sheets.2,4
  • Treat inhalation injury as indicated: intubate, order aggressive pulmonary toilet + bronchodilator (albuterol) +/- N-acetylcysteine, aerosolized heparin, aerosolized TPA, recombinant human antithrombin, surfactant, inhaled NO, or ECMO if required (the majority of this will be addressed in an ICU setting).2
  • Consider escharotomy or lateral canthotomy if concern for hypoventilation or compartment syndromes.4
  • After initial stabilization, follow the American Burn Association (ABA) Guidelines for the transfer of patients to designated burn centers. Suggested criteria for transfer can be found on the ABA webpage: http://www.ameriburn.org/BurnCenterReferralCriteria.pdf

A few words on steroids and antibiotics – Today there is no data to support steroid administration in the setting of inhalation injury.2 Prophylactic antibiotics are also withheld in the setting of burn injuries as several studies have demonstrated their administration as promoting systemic fungal infection.2

Morality – The Baux Score (% TBSA + Age) has historically been utilized as a predictor of mortality.2


In treating a burn patient:

  1. Follow ATLS guidelines in the initial evaluation and resuscitation of the burn patient, with special attention to unique airway considerations.
  2. Evaluate the patient for signs of toxic exposures, particularly carbon monoxide and cyanide.
  3. The burn patient requires comprehensive care. Follow ABA guidelines when considering transfer.


  1. DeKoning E. Thermal Burns. In: Tintinalli JE, Stapczynski J, Ma O, Yealy DM, Meckler GD, Cline DM. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e. New York, NY: McGraw-Hill; 2016. http://accessmedicine.mhmedical. com.foyer.swmed.edu/content.aspx?bookid=1658&Sectionid=109438787.
  2. Friedstat J, Endorf FW, Gibran NS. Burns. In: Brunicardi F, Andersen DK, Billiar TR, Dunn DL, Hunter JG, Matthews JB, Pollock RE. eds. Schwartz’s Principles of Surgery, 10e. New York, NY: McGraw-Hill; 2014. http://accessmedicine.mhmedical. com.foyer.swmed.edu/content.aspx?bookid=980&Sectionid=59610849.
  3. Drigalla D, Gemmill J. Chapter 45. Burns & Smoke Inhalation. In: Stone C, Humphries RL. eds. CURRENT Diagnosis & Treatment Emergency Medicine, 7e.New York, NY: McGraw-Hill; 2011.http://accessmedicine.mhmedical.com.foyer.swmed.edu/content.aspx?bookid=385&Sectionid=40357261.
  4. Latenser BA. Critical Care of the Burn Patient. In: Hall JB, Schmidt GA, Kress JP. eds. Principles of Critical Care, 4e. New York, NY: McGraw-Hill; 2015.http://accessmedicine.mhmedical.com. foyer.swmed.edu/content.aspxbookid=1340&Sectionid=80027724.
  5. Remote Primary Health Clinic Manuals. Burns. 2014. Available from: https://rphcm.allette.com.au/publication/cpm/Burns.html
  6. American Burn Association. Advanced Burn Life Support Course Provider Manual. American Burn Association 2007.
  7. Lawrence A1, Faraklas I, Watkins H, Allen A, Cochran A, Morris S, Saffle J. Colloid administration normalizes resuscitation ratio and ameliorates “fluid creep”. J Burn Care Res. 2010 Jan-Feb;31(1):40-7. doi: 10.1097/BCR.0b013e3181cb8c72. PMID 20061836.
  8. Saffle JI. The phenomenon of “fluid creep” in acute burn resuscitation. J Burn Care Res. 2007 May-Jun;28(3):382-95. PMID 17438489

Bi-level Ventilation: Who Needs it and Who Doesn’t? Pearls and Pitfalls

Authors: Robert Goodnough, MD (EM Resident Physician, UCSF-ZSFG Emergency Medicine Residency Program), Karla Canseco, MD (EM Resident Physician, UCSF-ZSFG Emergency Medicine Program), and Marianne Juarez, MD (Assistant Clinical Professor of Emergency Medicine, UCSF-ZSFG Medical Center) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)


A 65 year-old presents to the emergency department (ED) via emergency medical services (EMS) due to respiratory distress that awakened him from sleep. EMS reports that, upon their arrival, the patient had an oxygen saturation of 85% on room air. Continuous positive airway pressure (CPAP) was provided to the patient and his oxygen saturation improved to 94%. The CPAP also improved the patient’s work of breathing.

On examination in the ED, the patient is tachypneic. He also demonstrates rales, supraclavicular retractions, and is in atrial fibrillation with heart rate (HR) in the 110s. His blood pressure (BP) is 205/104 mmHg.  A nitroglycerin drip is ordered and respiratory therapy is called to place the patient on bi-level positive airway pressure (BiPAP). At this point, one of your seasoned colleagues mentions that he remembered a time when all heart failure patients were intubated.

You tuck your endotracheal (ET) tube into your back pocket and you wonder if your patient will eventually need this…


Noninvasive Positive Pressure Ventilation (NIPPV) is mechanical ventilation that is provided via nasal prongs, a full or oral-nasal facemask, or mouthpiece.  Different modes of mechanical ventilation are available, but the most commonly used methods are CPAP and BiPAP1.  The majority of evidence in NIPPV does not differentiate between CPAP and bi-level, or other modes of NIPPV, and the majority of outcomes and data are applied to NIPPV as a generalized intervention.


(photo courtesy of Kai Romero, MD)

Why avoid endotracheal intubation?

Endotracheal intubation is a life-saving intervention when applied skillfully, but its attendant risks are well described.  Staving off intubation has been shown to decrease complications such as hypotension, arrhythmias, death, and nosocomial infections. Intubation also places patients at an increased need for sedation and invasive procedures2. Noninvasive ventilation has become commonplace in the ED to treat respiratory failure and prevent intubation1.

Some Definitions:

  • CPAP: applies constant pressure throughout the breathing cycle to increase functional residual capacity (FRC) by recruiting alveoli, decreasing work of breathing, and improving oxygenation. It is best given in hypoxemic patients 1,3.
  • PEEP/EPAP: Positive End Expiratory Pressure, which is the alveolar pressure before inspiratory flow begins. Adding PEEP helps decrease the amount of work required to initiate a breath. It also helps to decrease atelectasis1,4.
  • Bi-level: Cycled ventilation between Inspiratory Positive Airway Pressure (IPAP) and Expiratory Positive Airway Pressure/PEEP1BiPAP supports ventilation and increases oxygenation.
  • Pressure Support: The difference between EPAP and IPAP is referred to as pressure support. Pressure support makes it easier to draw larger tidal volumes1,4.

Applications for NPPV/Bi-level

1. Chronic Obstructive Pulmonary Disease (COPD)

In COPD, acute respiratory failure manifests as hypoxic, hypercapneic respiratory failure with collapse of small airways. Hyperinflation also occurs. Acute respiratory failure from COPD leads to increased work of breathing, acidosis, altered mental status, and ultimately coma, decompensation, and death5

Bi-level ventilation is a primary treatment option in COPD with good evidence for success5. When compared to usual medical care, bi-level ventilation decreases the risk of death (relative risk reduction 48%) and intubation rates (RRR 60%)5.

Number Needed to Treat (NNT) for mortality benefit = 10

NNT to prevent intubation = 4

Furthermore, when comparing patients with moderate and severe acidosis, bi-level ventilation decreased mortality, rates of intubation, and lengths of stay. It also improved work of breathing, acidosis, and PaC02 levels. Finally, regarding these outcomes, there were no significant differences between more and less acidotic patients at admission5,6.

Indications for NIPPV/bi-level ventilation6

1.      pH <7.35or PaC02 >45 mmHg

2.      Severe dyspnea with signs of increased work of breathing

3.      Caution: In severe respiratory acidosis (pH <7.25), failure rates of NIPPV may be as high as 50%1

Common Initial Settings:

  • IPAP 8-20 cm H2O (up to 30 cm H20)
  • EPAP 2-6 cm H2O to overcome intrinsic airway collapse3,5,7
  • Begin with either high IPAP and then titrate down, or low and titrate high. Both are reasonable, but require close monitoring to meet ventilation goals.7 Each patient is different.
  • Endpoints for physiologic improvement:  at 1 hour, reassessment should be made. Decisions regarding treatment failure, worsening clinical status of bi-level should be made early.5

2. Cardiogenic Pulmonary Edema (CPO)

Acute cardiogenic pulmonary edema is a common and potentially fatal cause of acute respiratory distress. CPO is related to a critical interaction between worsening left ventricular systolic function and an acute increase in systemic vascular resistance that results in rapid accumulation of fluid in the interstitium of the lung. This leads to decreased lung compliance, increased airway resistance, hypoxia, decreased diffusion capacity, and hypercarbia from muscle fatigue8.

Bi-level offers the advantage of improving both cardiac and pulmonary function by providing pressure support with IPAP and EPAP/PEEP. IPAP assists ventilation, which decreases the work of breathing and assures adequate ventilation. The EPAP/PEEP increases the FRC by recruiting collapsed alveoli, improving oxygenation, and helping to force interstitial fluid back into the pulmonary vasculature9,10.

Bi-level ventilation also increases intrathoracic pressure, which can lead to decreased left ventricular (LV) end diastolic volume. This results in decreased afterload and increased LV ejection fraction/stroke volume. Thus, the heart muscle is stretched less, and placed at a steeper part of the Starling curve. This results in stronger LV contractions, and reductions in BP and HR11.


(Figure: in the failing heart, NIPPV both decreases preload and also shifts the Starling curve (decreases afterload) to augment cardiac performance)12,13

Common Initial Settings:

·         IPAP: 10 to 20 cm H20

·         EPAP: 5 to 10 cm H20

·         I:E ratio of IT to ET and is usually set at 1:3 or 1:4 (Inspiratory to Expiratory ratio)

Evidence for Bi-level ventilation in CPO:

Unfortunately, most of the evidence for NIPPV for CPO is centered on CPAP with few trials comparing the two modalities (CPAP and bi-level) head-to-head.

In a Cochrane review looking at NIPPV in CPO, CPAP alone has been proven to decrease intubation rates and to decrease in-hospital mortality, without the same benefit seen using bi-level ventilation14.

In the treatment of CPO, controversy regarding the safety of bi-level ventilation stems mainly from a single small study comparing the two NIPPV modalities. This study showed a more rapid improvement in vital signs, dyspnea and arterial blood gas (ABG) results with bi-level, but it also showed higher rates of myocardial infarction (MI) with bi-level ventilation15.  However, subsequent trials comparing CPAP and bi-level showed no difference in MI rates, but decreased intubation rates for those treated with bi-level, especially in patients presenting with hypercarbia16,17.

A trend that holds true is that bi-level leads to rapid improvement in physiological parameters such as respiratory rate, pH, PaCO2, PaO2, HR, work of breathing, afterload, preload, cardiac index, and ejection fraction. However,  more studies need to be performed to show a clear benefit in patient mortality and consistently decreased intubation rates18–21.

Indications for NIPPV in CPO:

1.      Increased work of breathing

2.      Hypercapnia and respiratory failure

3. Asthma

In asthma, NIPPV/bi-level ventilation might help to overcome intrinsic auto-PEEP, to decrease ventilation/perfusion (V/Q) mismatch by increased recruitment of alveoli, and to have a direct bronchodilatory effect in order to decrease work of breathing22.

In the mechanical ventilation of an asthmatic, one should carefully weigh the risk of critical error if the patient is not allowed a prolonged period of expiration in order to prevent “auto-PEEP”. Auto-PEEP is a condition where inhaled breaths are progressively delivered to lungs that have not returned to their FRC. This can subsequently lead to life-threatening hypotension and severe barotrauma, such as pneumothorax2.

Complications from intubation in a severe asthmatic can be severe, including cardiovascular collapse, pneumothorax, and prolonged intubation23.  However, a systematic review comparing NIPPV to medical care did not find a significant benefit to mortality or decreased rates of intubation, though these end points were likely limited by small numbers of patients studied in the intervention22.

Given the risks of intubation, and the purported physiologic benefits of bi-level ventilation to a severe asthmatic, NIPPV is a reasonable treatment strategy.  However, this should be done in tandem with medical management in carefully selected and monitored patients. Of note, NIPPV in asthma has not yet achieved the standard of care.

Indications for NIPPV in Asthma:

1.      As a carefully applied adjunct to medical management in refractory asthma

4. Acute Respiratory failure (no pre-existing chronic lung disease)

The benefits of NIPPV is not clear in undifferentiated acute respiratory failure and the evidence is often conflicting.  The use of NIPPV in undifferentiated acute respiratory failure (ARF) has shown similar mortality rates to conventional ventilation, but it has also demonstrated decreased intubation rates. On the other hand, decreased intubation rates may not apply to those with pneumonia or non-hypercapneic respiratory failure (PNA)24.

A recent multi-center trial showed no decrease in intubation rates for non-hypercapneic ARF (64% PNA) in those without chronic lung disease when compared to high flow or regular oxygen. Additionally, 90 day mortality was decreased in the high flow oxygen group compared to NIPPV. Also, delayed intubation via NIPPV did not show an association with increased mortality25.

Method of delivery and severity of illness likely affect mortality rates in patients with adult respiratory distress syndrome (ARDS) treated with NPPV, as a recent RCT showed decreased 90 day mortality in patients ventilated with helmeted NPPV compared to face mask NPPV26.


1.      There are no clearly recommended indications and it should be on a case by case basis.

5. Blunt Thoracic Trauma

In a recent meta-analysis of 219 patients with thoracic trauma, NIPPV decreased intubation rates, improved oxygenation, decreased infection rates and showed mortality rates of 3% vs 22.9% in “standard management,” which was CPAP or face mask oxygen27.

6. Special Populations:

NIPPV decreases intubation rates and in-hospital mortality when applied to acute hypoxic respiratory failure in immunocompromised patients1,28.

It may also provide a benefit to patients with palliative care needs in whom endotracheal intubation is not within their goals of care, with some studies showing reversal of acute respiratory failure and return to home1,28,29.

The use of NPPV in the ARF of decompensation of neuromuscular disease is controversial, and may not be indicated in those with rapidly progressive disease29.

Pre-oxygenation For Intubation:

Much of the focus has been on avoiding intubation, but in critically ill patients, intubation and mechanical ventilation can be life-saving; to intubate an unstable patient is perilous, with desaturation, arrhythmia, cardiovascular collapse and cardiac arrest as well recognized entities30.

Pre-oxygenation prior to intubation is the standard of care to prevent life threatening complications during intubation.  Some patients display refractory hypoxia in the face of usual facemask pre-oxygenation, and failure to reach 93-95% Sp02 prior to intubation places the patient at risk for desaturation and apnea during the procedure31.

NIPPV has been shown to decrease desaturation rates in refractory hypoxia during pre-oxygenation for intubation and should be strongly considered for pre-oxygenation prior to intubation in refractory hypoxia30–32.


  1. Positive Pressure is not everything. Do not forget medical management
  2. Bi-level ventilation is an early “go-to” in moderate to severe COPD exacerbations
  3. Experienced respiratory therapists (RTs) and staff are critical to the success of non-invasive ventilation
  4. Once applied, reassess your patient frequently and be ready to adjust!
  5. Can be used to stave off intubation at the end of life
  6. Consider for pre-oxygenation prior to intubation


  1. Positive pressure can cause hypotension and decompensation if blindly applied
  2. Do not place a pressure mask on a damaged face or a fluid filled mouth
  3. Do not delay necessary intubation
  4. Do not let your patient Auto-PEEP
  5. Your severely acidotic patient is at high risk for failure: be ready to intubate.
  6. If your patient is not awake, then the patient should be intubated.

 Who Needs It?

  1. Patients with moderate to severe COPD exacerbations
  2. Those patients with cardiogenic pulmonary edema with increased work of breathing or hypercapnia
  3. Patients with isolated blunt thoracic trauma
  4. The immunocompromised patient with hypoxic respiratory failure
  5. Patients who require pre-oxygenation prior to intubation

Who Does Not?

  1. Altered Mental Status
  2. Facial Trauma/Can’t Handle their own secretions

Gray Zones?

  1. Asthma
  2. Neuromuscular Disease
  3. Undifferentiated Hypoxic Respiratory Failure

References / Further Reading

1. Aboussouan, L. S. & Ricaurte, B. Noninvasive positive pressure ventilation: Increasing use in acute care. Cleve. Clin. J. Med. 77, 307–316 (2010).

2. Leatherman, J. Mechanical ventilation for severe asthma. Chest 147, 1671–1680 (2015).

3. Bolton, R. & Bleetman, A. Non-invasive ventilation and continuous positive pressure ventilation in emergency departments: where are we now? Emerg. Med. J. EMJ 25, 190–194 (2008).

4. Appendini, L. et al. Physiologic effects of positive end-expiratory pressure and mask pressure support during exacerbations of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 149, 1069–1076 (1994).

5. Ram, F. S. F., Picot, J., Lightowler, J. & Wedzicha, J. A. Non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. CD004104 (2004). doi:10.1002/14651858.CD004104.pub2

6. Pauwels, R. A., Buist, A. S., Calverley, P. M. A., Jenkins, C. R. & Hurd, S. S. Global Strategy for the Diagnosis, Management, and  Prevention of Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 163, 1256–1276 (2001).

7. Prinianakis, G., Delmastro, M., Carlucci, A., Ceriana, P. & Nava, S. Effect of varying the pressurisation rate during noninvasive pressure support ventilation. Eur. Respir. J. 23, 314–320 (2004).

8. Wiesen, J., Ornstein, M., Tonelli, A. R., Menon, V. & Ashton, R. W. State of the evidence: mechanical ventilation with PEEP in patients with cardiogenic shock. Heart Br. Card. Soc. 99, 1812–1817 (2013).

9. Cross, A. M. Review of the role of non-invasive ventilation in the emergency department. J. Accid. Emerg. Med. 17, 79–85 (2000).

10. Peter, J. V., Moran, J. L., Phillips-Hughes, J., Graham, P. & Bersten, A. D. Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis. Lancet Lond. Engl. 367, 1155–1163 (2006).

11. Sheldon, R. Congestive heart failure and noninvasive positive pressure ventilation. Emerg. Med. Serv. 34, 64–67 (2005).

12. Figueroa, M. S. & Peters, J. I. Congestive heart failure: Diagnosis, pathophysiology, therapy, and implications for respiratory care. Respir. Care 51, 403–412 (2006).

13. Shekerdemian, L. & Bohn, D. Cardiovascular effects of mechanical ventilation. Arch. Dis. Child. 80, 475–480 (1999).

14. Vital, F. M. R., Ladeira, M. T. & Atallah, A. N. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database Syst. Rev. CD005351 (2013). doi:10.1002/14651858.CD005351.pub3

15. Mehta, S. et al. Randomized, prospective trial of bilevel versus continuous positive airway pressure in acute pulmonary edema. Crit. Care Med. 25, 620–628 (1997).

16. Nava, S. et al. Noninvasive ventilation in cardiogenic pulmonary edema: a multicenter randomized trial. Am. J. Respir. Crit. Care Med. 168, 1432–1437 (2003).

17. Gray, A. J. et al. A multicentre randomised controlled trial of the use of continuous positive airway pressure and non-invasive positive pressure ventilation in the early treatment of patients presenting to the emergency department with severe acute cardiogenic pulmonary oedema: the 3CPO trial. Health Technol. Assess. Winch. Engl. 13, 1–106 (2009).

18. Park, M. et al. Oxygen therapy, continuous positive airway pressure, or noninvasive bilevel positive pressure ventilation in the treatment of acute cardiogenic pulmonary edema. Arq. Bras. Cardiol. 76, 221–230 (2001).

19. Crane, S. D., Elliott, M. W., Gilligan, P., Richards, K. & Gray, A. J. Randomised controlled comparison of continuous positive airways pressure, bilevel non-invasive ventilation, and standard treatment in emergency department patients with acute cardiogenic pulmonary oedema. Emerg. Med. J. EMJ 21, 155–161 (2004).

20. Levitt, M. A. A prospective, randomized trial of BiPAP in severe acute congestive heart failure. J. Emerg. Med. 21, 363–369 (2001).

21. Pang, D., Keenan, S. P., Cook, D. J. & Sibbald, W. J. The effect of positive pressure airway support on mortality and the need for intubation in cardiogenic pulmonary edema: a systematic review. Chest 114, 1185–1192 (1998).

22. Ram, F. S. F., Wellington, S., Rowe, B. & Wedzicha, J. A. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database Syst. Rev. CD004360 (2005). doi:10.1002/14651858.CD004360.pub3

23. Landry, A., Foran, M. & Koyfman, A. Does Noninvasive Positive-Pressure Ventilation Improve Outcomes in Severe Asthma Exacerbations? Ann. Emerg. Med. 62, 594–596

24. Honrubia, T. et al. Noninvasive vs conventional mechanical ventilation in acute respiratory failure : A multicenter, randomized controlled trial. Chest 128, 3916–3924 (2005).

25. Frat, J.P. et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N. Engl. J. Med. 372, 2185–2196 (2015).

26. Patel, B. K., Wolfe, K. S., Pohlman, A. S., Hall, J. B. & Kress, J. P. Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA 315, 2435–2441 (2016).

27. Chiumello, D., Coppola, S., Froio, S., Gregoretti, C. & Consonni, D. Noninvasive ventilation in chest trauma: systematic review and meta-analysis. Intensive Care Med. 39, 1171–1180 (2013).

28. Hill, N. S., Brennan, J., Garpestad, E. & Nava, S. Noninvasive ventilation in acute respiratory failure. Crit. Care Med. 35, 2402–2407 (2007).

29. Mas, A. & Masip, J. Noninvasive ventilation in acute respiratory failure. Int. J. Chron. Obstruct. Pulmon. Dis. 9, 837–852 (2014).

30. Mosier, J. M. et al. The Physiologically Difficult Airway. West. J. Emerg. Med. 16, 1109–1117 (2015).

31. Weingart, S. D. & Levitan, R. M. Preoxygenation and prevention of desaturation during emergency airway management. Ann. Emerg. Med. 59, 165–175.e1 (2012).

32. Baillard, C. et al. Noninvasive ventilation improves preoxygenation before intubation of hypoxic patients. Am. J. Respir. Crit. Care Med. 174, 171–177 (2006).


Stable Monomorphic Ventricular Tachycardia Management in the ED

Authors: Brit Long, MD (@long_brit, EM physician at SAUSHEC) and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) // Edited by: Jennifer Robertson, MD, MSEd

You are five minutes into your shift, and the charge nurse asks you to immediately see a patient who was just roomed. The patient is a 62-year-old male with a history of coronary artery disease (CAD), hypertension (HTN), hyperlipidemia (HLD) and two prior myocardial infarctions (MIs). He complains of lightheadedness, but otherwise feels well without chest pain or dyspnea. He is actually not sure why he was rushed back so quickly. The technician hands you an electrocardiogram (ECG) which displays a wide complex, monomorphic rhythm at 134 beats per minute (bpm). With the exception of a rapid heart rate, the patient’s vital signs are unremarkable, with a blood pressure (BP) of 144/70 and a respiratory rate (RR) of 17 breaths per minute.

He does not show any signs of hemodynamic instability, and his ECG is consistent with monomorphic ventricular tachycardia. What are the best treatment options for this patient?


Ventricular tachycardia (VT) and ventricular fibrillation (VF) cause approximately 300,000 deaths per year in the United States (US) and account for 5.6% of all mortality.1 VT is considered the most common wide complex tachycardia.2-7 Risk factors for VT include known cardiac ischemia, male gender, and older age. Underlying causes of VT include ischemic heart disease, structural heart disease (cardiomyopathy), congenital heart disease, channelopathies, electrolyte derangements, sympathomimetic agents, digitalis toxicity, and infiltrative cardiomyopathy.2-6,8

Wide complex tachycardias are defined by a rate greater than 100 bpm and a QRS complex duration greater than 120 milliseconds (ms). The differential diagnosis of wide complex tachycardia includes supraventricular tachycardia with aberrant ventricular conduction, preexcited tachycardia in patients with Wolff-Parkinson-White syndrome, ventricular tachycardia, toxic/metabolic derangement, pacemaker-related WCT, and artifact.3-6 VT accounts for 80% of wide complex tachycardias, SVT with aberrant conduction accounts for the other, approximately 20% of cases.9,10

The rhythm of VT originates distal to the bundle of His in the ventricular myocardium. Actual sites of origin may include the ventricular myocardium, distal conduction system beyond the bundle of His, or both. VT is associated with ventricular rates of > 120 bpm and QRS complex intervals > 120 ms.3-6  The majority of patients with VT possess an area of fibrotic tissue in the myocardium. 3-6,10  This scar usually results from prior myocardial infarction or ischemic cardiomyopathy, while a small minority of patients may have normal myocardium with no structural disease.10,11

The classification of ventricular tachycardia is based on several factors: ECG appearance, duration of VT, and most importantly, hemodynamic status of the patient. 

– Monomorphic VT is a wide complex rhythm with a QRS duration greater than 120 ms. It originates from a single focus and is identical from beat to beat.

– Polymorphic VT varies from beat to beat.

– Non-sustained VT occurs for less than 30 seconds.

– Sustained VT lasts longer than 30 seconds.3-5,12

– A patient with VT who is unstable demonstrates evidence of hemodynamic compromise including hypotension, altered mental status, chest pain, or heart failure but is awake with a pulse. If the patient is unresponsive or pulseless, then cardiac arrest is present.

– A stable patient with VT shows no signs of hemodynamic compromise.3-6,13

The medical management of ventricular tachycardia is controversial, specifically for stable, monomorphic VT.  Multiple options exist, and expert recommendations have undergone multiple modifications.

 Current VT Management Guidelines

The 2000 American Heart Association (AHA) guidelines for Advanced Cardiac Life Support (ACLS) recommended procainamide or sotalol (IIa) over the use of amiodarone or lidocaine (IIb) in the setting of stable, monomorphic VT with preserved ejection fraction (EF).13

In patients with decreased EF, amiodarone and lidocaine received IIb recommendations.

The American College of Cardiology (ACC)/AHA/European Society of Cardiology (ESC) 2006 modifications gave amiodarone a IIa recommendation for stable VT resistant to procainamide.14,15 Per the AHA Advanced Cardiovascular Support (ACLS) algorithm, amiodarone is the only anti-dysrhythmic mentioned for use in patients with VT (class IIb).15 However, the AHA still recommended procainamide in patients who have preserved EF and a normal QT interval (class IIa). Lidocaine was also recommended as a second line agent (class indeterminate). The AHA notes sotalol can be given but only with expert consultation.15 The European resuscitation guidelines also recommend amiodarone for treatment of stable, monomorphic VT.16

 In 2010, further modifications were made by the AHA, where sotalol was given a class IIb recommendation.17 The 2015 update did not change the recommendations for procainamide and amiodarone.18

Despite these recommendations, direct-current cardioversion is the most effective therapy, supported by numerous studies.4,6,18-20  If possible, this should be the first-line treatment.

Management of Unstable VT

The management of patients with unstable monomorphic or polymorphic VT requires immediate synchronized direct-current cardioversion. If recurrent VT occurs, continue to electrically cardiovert. In addition, a patient with shock resistant unstable VT should receive amiodarone 300 mg IV with a second bolus of 150 mg IV.4,6,15,17,18

 Management of Stable VT

Hemodynamically stable patients should be approached by first evaluating whether the VT is monomorphic or polymorphic. If the rhythm is polymorphic with normal QT interval, treatment is the same as monomorphic VT. Prolonged QT with polymorphic VT is concerning for Torsades de pointes. Magnesium sulfate, isoproterenol, pacing, or a combination of these treatments is required. Avoid procainamide and amiodarone in this setting, which can prolong the QT interval further.21

Several medications can be used for the management of stable, monomorphic VT. This post will evaluate several of these medications. Of note, we will not address suppression of stable VT, but rather termination of the dysrhythmia.


Lidocaine is a class Ib antidysrhythmic. The medication antagonizes fast voltage-gated sodium channels, preventing depolarization and action potential transmission. Lidocaine is dosed at 1 to 1.5 mg/kg IV initially and repeated at 0.5 to 0.75 mg/kg every 5 to 10 minutes.  Lidocaine can have numerous side effects that may affect the cardiovascular, gastrointestinal and central nervous systems. Hypotension, thrombophlebitis at the infusion site, tinnitus, dyspnea, bronchospasm, and allergic reactions can also occur from lidocaine therapy.4,6,14-120,22,23


Amiodarone is a class III antidysrhythmic that prolongs phase 3 of the cardiac action potential.  The medication has other antidysrhythmic effects, similar to classes Ia, II, and IV.  The mechanism of this medication is complex: it increases the refractory period of sodium and potassium channels and slows intracardiac action potentials, similar to beta blockers and calcium channel blockers. Dosing is 150 mg IV over 10 minutes, followed by 1 mg/minute for 6 hours and 0.5mg/minute for at least 18 hours. Contraindications include prior hypersensitivity, severe sinus node dysfunction, second and third degree heart block, cardiogenic shock, and syncope from heart block. The medication affects multiple organs and organ systems: pulmonary (interstitial lung disease, pulmonary fibrosis), thyroid (hypothyroidism and hyperthyroidism), ophthalmologic (optic neuropathy, keratopathy, vision changes), liver (jaundice, hepatitis, hepatomegaly), skin (discoloration), neuropathy, gynecomastia, and epididymitis. 4,6,14-18,20,24


Procainamide is a class Ia antidysrhythmic that induces a rapid block of cardiac sodium channels. The blockage of sodium channels occurs intracellularly and extracellularly. Procainamide slows conduction velocity and increases the refractory period.  Classically, the medication is dosed at 15 to 18 mg/kg IV as a slow infusion over 25 to 30 minutes, but the 2015 ACLS guidelines recommend a max dose of 17 mg/kg.18  Other studies have since modified this dosing regimen, which is discussed below. Several options are present for rate of infusion: either 20 to 50 mg/minute or 100 mg every 5 minutes may be given until resolution of VT, hypotension or QRS widening by 50% of its original length occurs. The infusion should also be stopped once a total dose of 17 mg/kg IV is reached.  Several side effects can occur while using procainamide, including worsening dysrhythmia, bradycardia, hypotension, drug fever, allergy, blood dyscrasias, and systemic lupus erythematosus. 4,6,14-20,25


Sotalol is a class III antidysrhythmic that targets potassium channels and delays ventricular relaxation. This increases the amount of time before another signal can be generated in the myocytes. The medication is also a non-selective competitive beta-adrenergic receptor blocker, decreasing production of cyclic AMP and the activation of calcium channels.26,27 Dosing is 1.5 mg/kg IV over 5 minutes. Contraindications include sick sinus syndrome, long QT syndrome, shock, asthma, potassium less than 4 meq/L, and poorly controlled heart failure. Side effects include weakness, dizziness, headache, bradycardia, palpitations, nausea/vomiting, and headache.4,6,27-30

On the horizon? Nifekalant

A medication recently developed and only currently used in Japan is nifekalant, a class III antidysrhythmic that selectively blocks potassium channels, prolonging the refractory period. It has no intrinsic β-blocking capability.31-34 This medication is thought to have rapid onset of action, rapid clearance and rapid reduction of the defibrillation threshold, while having no negative inotropic effects. Nifekalant is dosed at 0.3-0.6 mg/kg IV, followed by an infusion rate of 0.15-0.50 mg/kg/hr IV. This medication has demonstrated efficacy in the termination and suppression of VT in multiple studies.  Rates of successful VT termination with utilization of this medication range from 48.4% to 80%.31-39 This medication may also improve the defibrillation ability of direct current.  Studies have also been conducted for ventricular fibrillation, shock-resistant ventricular fibrillation, and hemodynamically unstable ventricular tachycardia. It has not been evaluated against procainamide. Adverse effects include QT interval prolongation and Torsades de pointes.31-39

Some Literature…

The majority of literature evaluates VT suppression, rather than VT termination. The studies evaluating the use of antidysrhythmic termination of VT suffer from significant heterogeneity in exclusion criteria, medications studied, and outcomes.40-46

Ho et al. 1994:  a randomized prospective trial including 33 patients with VT based on ECG criteria.41

– Investigators compared sotalol 100mg IV over 5 minutes and lignocaine (otherwise known as lidocaine) 100 mg IV over 5 minutes. 41

– Outcome was VT termination in 15 minutes or hemodynamic deterioration.

Sotalol was more effective at VT termination, 69% versus 18% (95% confidence interval for absolute difference of 51%, 22-80%, p = 0.003).

– One patient in each group required electrical cardioversion. The authors concluded sotalol was more effective.40,41

Gorgels et al 1996: a randomized prospective study of 29 patients with VT based on ECG diagnosis.42 Investigators excluded patients with acute myocardial infarction and hemodynamic instability.

– Primary outcome consisted of VT termination in 15 minutes.

– The medications studied were procainamide 10mg/kg IV at 100 mg/min and lidocaine 1.5 mg/kg IV over 2 minutes.

Procainamide resulted in VT termination in 12 of 15 patients, while lidocaine only terminated 3 of 14. Procainamide also stopped VT in 8 of 11 patients in which lidocaine was ineffective.40,42

Manz et al. 1988:  a randomized, prospective trial. VT diagnosis was based on ECG or electrophysiological confirmation of VT.43

– Primary outcome was VT termination.

– Investigators compared ajmaline 50-75 mg IV over 3-5 minutes and lidocaine 100-200 mg IV over 3-5 minutes.43

Ajmaline terminated VT in 10 of 15 patients, but lidocaine only terminated VT in 2 of 16 patients, bringing into question the efficacy of lidocaine.

– Both medications were well tolerated.40,43

 Marill et al 2010:  a retrospective, observational trial, unlike the prior studies. The investigators compared amiodarone and procainamide, with inclusion of 83 patients on ECG criteria.44

– Primary outcome was VT termination within 20 minutes.

– Amiodarone was dosed at 150 mg IV with a minimum rate of 10 mg/min, and procainamide was dosed at 500 mg IV at a minimum rate of 15 mg/min.

Rates of VT termination were 25% and 30% for amiodarone and procainamide, respectively, with an adjusted odds of termination of 1.2 (95% confidence interval [CI] =0.4 to 3.6) when comparing procainamide to amiodarone.

– When comparing the two agents as initial agents alone, termination occurred in 8/34 patients receiving amiodarone (24%, 95% CI = 11% to 41%) and in 4/7 patients with procainamide (57%, 95% CI 18% to 90%).

– Of the patients receiving infusion, 35 of 66 amiodarone patients (53%, 95% CI=40 to 65%) and 13 of 31 procainamide patients (42%, 95% CI=25 to 61%) required electrical therapy.40,44

Komura et al. 2010: included 90 patients based on ECG criteria, comparing procainamide and lidocaine.45 No patients with chest pain or acute myocardial infarction were included.45

– Outcome was termination of VT or hemodynamic deterioration.

– Procainamide was dosed at 100 mg IV every 1 to 2 minutes to a maximum of 800 mg IV versus lidocaine at 50 mg IV to a maximum of 150 mg IV.

– Medications were discontinued if VT was terminated, maximum dosage was reached, or if the patient experienced hemodynamic decompensation.

VT was stopped in 53/70 patients receiving procainamide (75.7%) and in 7/20 patients receiving lidocaine (35.0%).

– Four of the patients who did not convert to normal sinus rhythm with lidocaine did convert with procainamide.

– QRS prolongation was seen with procainamide, but not with lidocaine.40,45

Ortiz et al. PROCAMIO study: just released this year, included 62 patients and compared procainamide with amiodarone.46

– Primary outcome was the presence of major cardiac adverse event (MACE) within 40 minutes after infusion initiation. MACE was defined by clinical signs of hypoperfusion, signs of heart failure, hypotension (systolic blood pressure ≤70 mmHg if the pre-treatment systolic pressure was ≤100 mmHg or systolic blood pressure ≤80 mmHg if the pre-treatment systolic pressure was > 100 mmHg), increase in HR of > 20 bpm with medication, and appearance of fast polymorphic VT.

– Fifteen patients (24%) experienced a MACE within 40 minutes of infusion discontinuation, though fewer events were found in patients receiving procainamide vs. amiodarone (9% vs. 41%, OR 0.1; 95% CI 0.03-0.6). Over a 24-hour period, adverse events occurred in 18% and 31% of the procainamide and amiodarone patients, respectively.

VT termination occurred in 67% of procainamide patients and 38% of amiodarone patients within 20 minutes of infusion initiation.

Among 49 patients with structural heart disease, MACE occurred in 11% procainamide and 43% amiodarone patients.46

These studies are summarized in the table below. If you’re interested in further evaluation of these studies, please see the “Deep Dive” section at the end of this post.

Table 1 – Comparison of Outcomes40-46

Study Sample Size Medications Outcome Relative Risk (95% CI) Number Needed to Treat (NNT) (95% CI)
Ho et al. 33 Lidocaine 100mg IV vs. Sotalol 100 mg IV Lidocaine 18% vs. Sotalol 69% 3.9 (1.3 to 11.5) 2.0 (1.2 to 4.5)
Gorgels et al. 29 Lidocaine 1.5 mg/kg IV vs. Procainamide 10 mg/kg IV Lidocaine 21% vs. Procainamide 80% 3.7 (1.3 to 10.5) 1.7 (1.1 to 3.4)
Manz et al. 31 Lidocaine 100 mg IV vs. Ajmaline 50 mg IV Lidocaine 13% vs. Ajmaline 67% 5.3 (1.4 to 20.5) 1.9 (1.2 to 3.9)
Marill et al. 41 Procainamide 500 mg IV vs. Amiodarone 150 mg IV Procainamide 57% vs. Amiodarone 24% 4.3 (0.8 to 23.6) 3.0 (-17.5 to 1.4)
Komura et al. 90 Lidocaine 50 mg IV up to 150 mg vs. Procainamide in 100 mg IV every 1-2 minutes (up to 800 mg) Lidocaine 35% vs. Procainamide 76% 2.2 (1.2 to 4.0) 2.5 (1.6 to 5.7)
Ortiz et al. 62 Procainamide 10mg/kg IV over 20 minutes vs. Amiodarone 5mg/kg IV over 20 minutes Procainamide 67% vs. Amiodarone 38% 1.8 (1.04 to 3.0) 3.5 (1.9 to 20.4)


VT Management Pearls

If possible, cardioversion should be performed. This is the most effective treatment, supported by guidelines and the literature.  If medications are utilized, physicians should carefully evaluate the patient’s hemodynamic status. If the patient becomes unstable at any point, direct current cardioversion is needed.4,6,18-20,24

In the U.S., if medical management is selected, procainamide provides the greatest efficacy and lowest risk of adverse outcomes.  Guidelines for infusion recommend an infusion rate of 20-50 mg/min IV;13-18 however, infusion time at this rate can take 30 minutes to reach adequate dosing. The results from Gorgels et al. and Komura et al. suggest that rates of 50-100 mg/min IV are efficacious and safe, while decreasing the time for needed monitoring.40,42,45

If the patient is experiencing acute ischemia or myocardial infarction, direct current cardioversion is needed. If medical management is selected, amiodarone or lidocaine may be more efficacious, but the poor literature support prevents the authors of this manuscript to recommend one medication over another.

Figure 1 – Stable Monomorphic VT Algorithm


Procainamide Pearls

Procainamide IV infusion requires monitoring of blood pressure and ECG. The QRS complex duration should be carefully analyzed before and during the infusion. Stop points of infusion include dysrhythmia discontinuation, hypotension, QRS prolongation greater than 50% of the original duration, a total of 1 gram is infused, or acceleration of the tachycardia. The most feasible dosing of procainamide includes a maximum dose of 10 mg/kg (maximum 1 g) IV at 100 mg/min over 10 minutes. This approach allows rapid loading of procainamide, compared to ACLS infusion of 20 mg/min until a maximum dose of 17 mg/kg is provided.

– Stable, monomorphic ventricular tachycardia is defined by a rate faster than 120 beats/min with QRS greater than 120 ms.

– Hemodynamically unstable VT requires immediate synchronized direct current cardioversion.

– Medical management of hemodynamically stable monomorphic VT is controversial. Direct current cardioversion is most efficacious.

– Guidelines for the treatment of VT from the AHA provide a IIa recommendation for procainamide, compared to a IIb recommendation for both amiodarone and sotalol.

– Studies evaluating procainamide, lidocaine, amiodarone, and sotalol suffer from poor design, difference in inclusion and exclusion criteria, small sample size, and outcome determination.

– PROCAMIO demonstrates procainamide’s efficacy.

– Procainamide demonstrates the greatest efficacy. If procainamide is selected, a maximum dose of 10 mg/kg (maximum 1 g IV) at 100 mg/min over 10 minutes should be provided with monitoring of blood pressure and ECG.

Ready for a Deep Dive?

All of the mentioned studies above (Ho et al., Gorgels et al., Manz et al., Marrill et al., Komura et al., and Ortiz et al.) used ECG for initial diagnosis of VT. These studies differed in whether patients with acute myocardial infarction (MI) were included.40-46 Gorgels et al., Ortiz et al., and Komura et al. did not include patients with MI,42,45,46 whereas the others did.41,43,44 All of these studies except one (Manz et al.) limited evaluation to spontaneous VT.40-46

Lidocaine was the most commonly studied medication, with similar dosing. Two of the studies evaluated procainamide and lidocaine,42,45  with two studies comparing procainamide and amiodarone.44  Dosing and rate of infusion of procainamide differed between studies, with Marrill et al. providing procainamide at maximum 500mg infusion.44 Komura et al. and Gorgels et al. used higher dosing ranges with fast infusions.42,45  These two studies found a NNT of approximately two for terminating VT with procainamide compared to lidocaine.42,45  Ortiz et al. utilized 10 mg/kg IV over 20 minutes, with a NNT of 3.5 when procainamide was compared to amiodarone.46 Four studies used a specified time of termination (15 to 20 minutes), and if termination of VT did not occur in this time, the medication was deemed unsuccessful.41,42,44,46 In terms of adverse effects from these studies, death occurred in four patients, one from a large myocardial infarction after termination of VT with sotalol. Hypotension occurred in a wide range, as Ortiz et al. found hypotension occurred in 24% of patients receiving procainamide and 48% of patients receiving amiodarone.46 Neurologic symptoms such as dizziness, paresthesias, headache, visual problems, and hearing changes occurred in approximately 16% of patients receiving lidocaine infusion.40-46

The current literature has few prospective trials with small sample sizes, as well as retrospective observational studies with selection bias and multiple confounders. The PROCAMIO study conducted by Ortiz et al., which is prospective and randomized, provides some of the strongest evidence supporting procainamide.46 A greater amount of literature exists evaluating the use of medications for suppression of VT. This post did not cover these studies. Another important aspect is the inclusion of patients with MI. Studies evaluating lidocaine and procainamide did not evaluate patients with acute MI, where lidocaine may block sodium channels in ischemic myocardium more effectively. These studies also did not calculate sample sizes needed for outcomes, and it is difficult to determine whether patients were properly randomized.40-46

 References/Further Reading:

  1. Chugh SS, Jui J, Gunson K, Stecker EC, John BT, Thompson B, et al. Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community. J Am Coll Cardiol 2004 Sep 15. 44(6):1268-75.
  2. Stewart RB, Bardy GH, Greene HL. Wide complex tachycardia: misdiagnosis and outcome after emergent therapy. Ann Intern Med 1986;104:766.
  3. Akhtar M, Shenasa M, Jazayeri M, et al. Wide QRS complex tachycardia. Reappraisal of a common clinical problem. Ann Intern Med 1988;109:905.
  4. Gupta AK, Thakur RK. Wide QRS complex tachycardias. Med Clin North Am 2001;85:245.
  5. Steinman RT, Herrera C, Schluger CD, et al. Wide QRS tachycardia in the conscious adult: Ventricular tachycardia is the most frequent cause. JAMA 1989;261:1013-1016.
  6. Delbridge TR, Yealy DM. Wide complex tachycardia. Emerg Med Clin North Am 1996;13:902-924.
  7. Herbert ME, Votey SR, Morgan MT, et al. Failure to agree on the electrocardiographic diagnosis of ventricular tachycardia. Ann Emerg Med 1996;271:35-38.
  8. Brugada J, Brugada R, Brugada P. Channelopathies: a new category of diseases causing sudden death. Herz 2007 May;32(3):185-91.
  9. Baerman JM, Morady F, DiCarlo LA, et al. Differentiation of ventricular tachycardia from supraventricular tachycardia with aberration: Value of the clinical history. Ann Emerg Med 1987;16:40-43.
  10. Josephson, ME. Electrophysiology of Ventricular Tachycardia: An Historical Perspective. J Cardiovasc Electrophysiol 2003;14:1134-1148.
  11. Stevenson WG. Catheter ablation of monomorphic ventricular tachycardia. Curr Opin Cardiol 2005;20(1):42-47.
  12. Morady F, Baerman JM, DiCarlo LA Jr, et al. A prevalent misconception regarding wide-complex tachycardias. JAMA 1985;254:2790.
  13. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 6: advanced cardiovascular life support: section 7: algorithm approach to ACLS emergencies: section 7A: principles and practice of ACLS. Circulation 2000;102(8 Suppl):I136–9.
  14. ACC/AHA/ESC. 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Card 2006;48:e247–346.
  15. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 7.3: Management of Symptomatic Bradycardia and Tachycardia. Circulation 2005;112:IV-67–77.
  16. Nolan JP, Soar J, Zideman DA, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 1. Executive summary. Resuscitation 2010;81:1219–76.
  17. Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122(Suppl 3): S729–67.
  18. Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, et al. Part 7: adult advanced cardiovascular life support: 2015 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132(Suppl 2): S444-S464.
  19. Lown B. Electrical reversion of cardiac arrhythmias. Br Heart J 1967;29:469–89.
  20. Atkins DL, Dorian P, Gonzalez ER, et al. Treatment of tachyarrhythmias. Ann Emerg Med 2001;37:S91–109.
  21. Passman R, Kadish A. Polymorphic ventricular tachycardia, long Q-T syndrome, and torsades de pointes. Med Clin North Am 2001;85(2):321-341.
  22. Carterall WA. Molecular mechanisms of gating and drug block of sodium channels” Sodium Channels and Neuronal Hyperexcitability. Novartis Foundation Symposia 2001;241:206–225.
  23. Sheu SS, Lederer WJ. Lidocaine’s negative inotropic and antiarrhythmic actions. Dependence on shortening of action potential duration and reduction of intracellular sodium activity. Circulation Research 1985 Oct;57(4):578–90.
  24. Tomlinson DR, Cherian P, Betts TR, et al. Intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment? Emerg Med J 2008;25:15–18.
  25. Zamponi GW, Sui X, Codding PW, French RJ. Dual actions of procainamide on batrachotoxin-activated sodium channels: open channel block and prevention of inactivation. Biophys J 1993;65(6):2324-2334
  26. Bertrix, Lucien et al. Protection against ventricular and atrial fibrillation by sotalol. Cardiovascular Research 1986;20:358-363.
  27. Edvardsson, N et al. Sotalol-induced delayed ventricular repolarization in man. European Heart Journal 1980;1:335-343.
  28. Antonaccio M, Gomoll A. Pharmacologic basis of the antiarrhythmic and hemodynamic effects of sotalol. Am J Cardiol 1993;72:27A-37A.
  29. Charnet P, et al. cAMP-dependent phosphorylation of the cardiac L-type Ca channel: A missing link? Biochimie 1995;77:957–962.
  30. Kassotis, J et al. Beta receptor blockade potentiates the antiarrhythmic actions of d-sotalol on re-entrant ventricular tachycardia in a canine model of myocardial infarction. Journal of Cardiovascular Electrophysiology 2003;14:1233-1244
  31. Naitoh N, Tagawa M, Yamaura M, Taneda K, Furushima H, Aizawa Y. Comparison of electrophysiologic effects of intravenous E-4031 and MS-551, novel class III antiarrhythmic agents, in patients with ventricular tachyarrhythmias. Jpn Heart J 1998; 39:457–467.
  32. Washizuka T, Chinushi M, Watanabe H, Hosaka Y, Komura S, Sugiura H, et al. Nifekalant hydrochloride suppresses severe electrical storm in patients with malignant ventricular tachyarrhythmias. Circ J 2005;69:1508–1513.
  33. Yusu S, Ikeda T, Mera H, Miyakoshi M, Miwa Y, Abe A, et al. Effects of intravenous nifekalant as a lifesaving drug for severe ventricular tachyarrhythmias complicating acute coronary syndrome. Circ J 2009;73:2021–2028.
  34. Pantazopoulos IN, Troupis GT, Pantazopoulos CN, Xanthos TT. Nifekalant in the treatment of life-threatening ventricular tachyarrhythmias. World Journal of Cardiology 2011;3(6):169-176.
  35. Sakurada H, Kobayashi Y, Sugi K, Katagiri T, Baba T, Enjoji Y, et al. Efficacy of intravenous doses of MS-551 for sustained ventricular tachycardia. J Clin Therap Med 1997;13:1773–1787.
  36. Aonuma K, Hiroe M, Nishimura S, Marumo F. Efficacy of intravenous doses of MS-551 for ventricular tachycardia after myocardial infarction. J Clin Therap Med 1997;13:1789–797.
  37. Katoh T, Tsunoo M, Mitsuhashi T, Atarashi H, Ino T, Kuroki S, et al. Phase I study of MS-551 (1)–A single intravenous injection study. J Clin Therap Med 1997;13:1659 – 1674.
  38. Katoh T, Mitamura H, Matsuda N, Takano T, Ogawa S, Kasanuki H. Emergency treatment with nifekalant, a novel class III anti-arrhythmic agent, for life-threatening refractory ventricular tachyarrhythmias: post-marketing special investigation. Circ J 2005 Oct;69(10):1237-43.
  39. Nakagawa K, Nakamura K, Kusano KF, et al. Use of Intravenous Amiodarone in the Treatment of Nifekalant-Resistant Arrhythmia: A Review of 11 Consecutive Cases with Severe Heart Failure. Pharmaceuticals 2011;4(6):794-803.
  40. deSouza IS, Martindale JL, Sinert R. Antidysrhythmic drug therapy for the termination of stable, monomorphic ventricular tachycardia: a systematic review. Emerg Med J 2015;32: 161–167.
  41. Ho DSW, Zecchin RP, Richards DAB, et al. Double-blind trial of lignocaine versus sotalol for acute termination of spontaneous sustained ventricular tachycardia. Lancet 1994;344:18–23.
  42. Gorgels AP, van den Dool A, Hofs A, et al. Comparison of procainamide and lidocaine in terminating sustained monomorphic ventricular tachycardia. Am J Cardiol Jul 1 1996;78:43–6.
  43. Manz M, Luderitz B. Emergency treatment of ventricular tachycardias: Ajmaline and lidocaine compared. Deutsche Medizinische Wochenschrift 1988;113:1317–21.
  44. Marill KA, deSouza IS, Nishijima DK, et al. Amiodarone or procainamide for the termination of sustained stable ventricular tachycardia: An historical multicenter comparison. Acad Emerg Med 2010;17:297–306.
  45. Komura S, Chinushi M, Furushima H, et al. Efficacy of procainamide and lidocaine in terminating sustained monomorphic ventricular tachycardia. Circ J May 2010;74:864–9.
  46. Ortiz M, Martin A, Arribas F, et a; PROCAMIO Study Investigators. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. Eur Heart J 2016 Jun 28. pii: ehw230. [Epub ahead of print]

The Young Cardiac Arrest Patient

Author: Joshua Bucher, MD (Assistant Professor of Emergency Medicine, Rutgers-RWJMS) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)


A 43-year-old male arrives in cardiac arrest. According to EMS, he was playing basketball when he suddenly clutched his chest. On EMS arrival, he was ashen, in severe respiratory distress and cardiogenic shock. A 12-lead EKG showed an anterior wall STEMI. On the way to the hospital, he went into cardiac arrest. After 10 minutes of chest compressions, intubation, defibrillations, and epinephrine administration, he is still in ventricular fibrillation.


The young cardiac arrest patient presents a difficult situation for the emergency provider. In general, younger patients are healthier than their geriatric counterparts. There are differences in physiology which may contribute to different prognosis and care.

Andersen et al. evaluated out-of-hospital cardiac arrest patients and found that there was no age in which resuscitation was futile; however, there was a progressive decline in good neurologic outcome after the age range of 45 – 64 years. The best age of survival with good neurologic outcome was 25 – 29 (46%).1

Unfortunately, sudden cardiac death (SCD) is possible at any age. Roberts et al. investigated the incidence of SCD in a Minnesota High School athlete population, and found 4 cardiac arrests out of 1,666,509 athletes, calculated to equal 0.24 deaths/100,000 athlete-years.2 They did not discuss the individual cases, but highlighted that sport-related SCD was uncommon, but present, in the high school athletic population.

Chugh et al. reviewed pre-hospital cardiac arrests and found that the proportion of arrests < the age of 65 in their community was only 25%. 50% of their cases over the age of 35 had the cause of death identified as coronary artery disease, on autopsy, of the non-survivors. Coronary artery disease was observed in 76% of all patients greater than the age of 35. The two patients less than 35 years of age suffered from WPW and congenital aortic disease. Unusually, 74% of the sudden cardiac arrests under the age of 35 had no discernible cause of death identified.3

One area of focus is the setting of exercise induced cardiac arrest. Berdowski et al. collected prospective data on their out of hospital cardiac arrest population. They found that exercise-related cardiac arrest was more likely in a younger patient population, male gender, in public, and with higher rates of bystander CPR and AED utilization. They were also more likely to present with shockable rhythms and demonstrated higher survival. They calculated an incidence of 0.3 exercise related SCD per 100,000 patient years in the less than 35 age group and 2.8 per 100,000 in non-exercise related SCD. Interestingly, all of their survivors of exercise related SCD were neurologically intact, regardless of age. Furthermore, they found that survival was higher in the group of 36 – 50-year-old men compared to less than or equal to 35 and greater than or equal to 51, when the arrest occurred in a public location, had bystander CPR, a public AED was used, shorter response time, and a shockable rhythm on EMS arrival. Overall, survival from exercise related SCD was maintained even when controlling for other variables.4

Marijon et al. also investigated sports and exercise related SCD in the out of hospital environment in France. 95% were male with a mean age of 46. Not surprisingly, bystander CPR and use of an AED were the strongest predictors of survival to discharge. Interestingly, 86.5% of the patients with sports-related SCD were reported to regularly exercise, highlighting that routine exercise does not eliminate the possibility of ACS causing SCD in a healthy population. SCD during team-related sports activities occurred at a significantly younger age than patients performing individual activities such as cycling or running (33 v 51, p <0.0001).  There was no correlation between age and survival.5

They also reported on the causes of cardiac arrest. In the young, competitive athlete population, 98% of the causes were related to a cardiac origin. 75% of the patients suffered from acute coronary syndrome. Other causes included hypertrophic cardiomyopathy, congenital cardiac diseases, dilated cardiomyopathy, myocarditis, arrhythmogenic right ventricular dysplasia, commotio cordis, prolonged QT syndrome, mitral valve prolapse, and WPW. There were 4 non cardiac causes identified – epilepsy, cerebral aneurysm rupture, stroke, and ruptured aortic aneurysm. The most common cause was idiopathic.

Marijon et al. investigated a second group of prospective SCD patients in the out of hospital environment in Portland over a 10-year period. They found similar results to the prior study; SCD due to exercise is rare, but an important cause in the younger population. They also found similar causes to the prior study.6

The CASPER study attempted to determine the cause of unexplained cardiac arrest survivors with preserved ejection fraction (with the assumption being that they did not suffer ACS as a cause of the arrest). After adequate testing and follow up, the most common causes were primary electrical disease (65% – Brugada, catecholaminergic ventricular tachycardia, early repolarization, long QT syndrome) and underlying structural issues (35% – ARVD, coronary spasm, dilated cardiomyopathy, myocarditis). The average age of the patients was 48.6; their average age at cardiac arrest was 41.5.7

Farioli et al. investigated SCD rates and causes in firefighters from several available databases. They found that, outside of coronary artery disease, common causes of arrest were hypertrophic cardiomyopathy, dilated cardiomyopathy, left ventricular hypertrophy, myocarditis, and valvular disorders.8

While this is mainly focused on medical causes of death, take care to consider other causes. According to the CDC, unintentional injury is the #1 cause of death in patients aged birth to 44. Suicide is the 2nd most common cause from ages 10 – 34. Homicide is the 3rd most common in ages 15 – 34. Other common causes are malignant neoplasms, and in younger children, congenital anomalies (although this article is focusing on adults). Overall, heart disease is the most common cause of death.9


Case resolution

The patient is defibrillated into sinus tachycardia. He is transferred to the catheterization lab, stented, undergoes therapeutic hypothermia, and walks out of the hospital 5 days later neurologically intact.

Table 1 – Etiologies of young cardiac arrest
Coronary artery disease

Hypertrophic cardiomyopathy

Dilated cardiomyopathy

Electrical conduction disorders (Brugada, catecholaminergic ventricular tachycardia, long QT syndrome, ARVD, WPW)

Congenital aortic disease

Coronary spasm



Screen Shot 2016-08-09 at 11.24.44 PM

Take Home Points

  1. Younger cardiac arrest patients often have different causes than older patients.
  2. Pay strong consideration to congenital abnormalities, conduction disorders, or other cardiac causes outside of coronary artery disease.
  3. Younger patients generally have better prognosis than their older counterparts.

References / Further Reading

  1. Andersen LW, Bivens MJ, Giberson T, et al. The relationship between age and outcome in out-of-hospital cardiac arrest patients. Resuscitation. 2015;94:49-54.
  2. Roberts WO, Stovitz SD. Incidence of sudden cardiac death in Minnesota high school athletes 1993-2012 screened with a standardized pre-participation evaluation. J Am Coll Cardiol. 2013;62(14):1298-1301.
  3. Chugh SS, Jui J, Gunson K, et al. Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community. J Am Coll Cardiol. 2004;44(6):1268-1275.
  4. Berdowski J, de Beus MF, Blom M, et al. Exercise-related out-of-hospital cardiac arrest in the general population: incidence and prognosis. European heart journal. 2013;34(47):3616-3623.
  5. Marijon E, Tafflet M, Celermajer DS, et al. Sports-related sudden death in the general population. Circulation. 2011;124(6):672-681.
  6. Marijon E, Uy-Evanado A, Reinier K, et al. Sudden cardiac arrest during sports activity in middle age. Circulation. 2015;131(16):1384-1391.
  7. Herman AR, Cheung C, Gerull B, et al. Outcome of Apparently Unexplained Cardiac Arrest: Results From Investigation and Follow-Up of the Prospective Cardiac Arrest Survivors With Preserved Ejection Fraction Registry. Circ Arrhythm Electrophysiol. 2016;9(1):e003619.
  8. Farioli A, Christophi CA, Quarta CC, Kales SN. Incidence of sudden cardiac death in a young active population. Journal of the American Heart Association. 2015;4(6):e001818.
  9. CDC. Ten Leading Causes of Death and Injury. 2016; http://www.cdc.gov/injury/wisqars/leadingcauses.html. Accessed 5/31, 2016.