Each year, approximately 300,000 people suffer out-of-hospital cardiac arrest (OHCA) in the United States.1 About one-third of these will have return of spontaneous circulation (ROSC), either en route to the hospital or in the emergency department (ED). Unfortunately, more than two-thirds of those with ROSC will not leave the hospital alive.
From optimizing tissue oxygen delivery to preventing hyperthermia, an in-depth look at the care of the post-arrest patient
Each year, approximately 300,000 people suffer out-of-hospital cardiac arrest (OHCA) in the United States.(1) About one-third of these will have return of spontaneous circulation (ROSC), either en route to the hospital or in the emergency department (ED). Unfortunately, more than two-thirds of those with ROSC will not leave the hospital alive.(2) During the arrest, care is algorithmic and is rarely aided by the expertise of the physician. Patient care technicians or paramedics perform chest compressions, the respiratory therapist administers breaths with a bag-valve mask, and the nurses administer medications and keep track of time. The physicians are all but superfluous during this period. It is after ROSC when the real challenge begins, and the physician’s training truly comes into play. Care of the post-arrest patient requires careful thought and vigilance to ensure optimal hemodynamics, correct reversible causes of arrest, and ultimately preserve neurologic funciton. The American Heart Association (AHA) has released guidelines to assist the physician in this process,(3) and this article will serve to summarize and update these guidelines.
Sedation and Paralysis
Patients resuscitated from cardiac arrest are frequently comatose or obtunded, and hence require intubation for both airway protection and ventilatory support. Endotracheal intubation is associated with discomfort and anxiety, and adequate analgesia and sedation are required. There is little evidence to guide pharmacology in this area, though it is most reasonable to use short-acting agents (such as midazolam and fentanyl) administered either as intermittent boluses or via continuous infusion, titrated to the desired level of sedation. It is also prudent to avoid drugs with significant cardiovascular depressant effects, such as propofol.
Paralysis may be necessary to control shivering in patients undergoing induced hypothermia, though the routine use of neuromuscular blockers is controversial. One study demonstrated improved survival (78% vs. 41%) among patients receiving 24 hours of continuous neuromuscular blockade, with an adjusted odds ratio for survival of 7.23 (95% CI 1.56-33.38).(4) Unfortunately, this was a post-hoc analysis of a small observational dataset likely subject to selection bias, and its results, while hypothesis-generating, are far from definitive. At least one randomized trial is underway to evaluate the role of routine neuromuscular blockade in therapeutic hypothermia(18), and may provide more robust evidence. The guidelines recommend that if neuromuscular blockade is used, continuous electroencephalographic monitoring should be considered in patients at risk for seizures, and the duration of paralysis should be kept to a minimum.
Hemodynamic collapse can, unfortunately, be rapid and profound, occurring within minutes to hours of ROSC. A deadly interplay of acidosis, reperfusion injury, proinflammatory mediators, and myocardial dysfunction make the post-arrest patient a veritable ticking time bomb. The prolonged tissue hypoperfusion associated with cardiac arrest leads to the release of multiple inflammatory mediators, including endotoxin, cytokines, and interleukins. A severe acidosis is also frequently present due to anaerobic metabolism, cell death, and hypoventilation. Arterial vasodilation occurs as a direct effect of proinflammatory mediators, while acidosis results in an attenuated response to endogenous and exogenous catecholamines. A combination of reperfusion injury, acidosis, and decreased calcium responsiveness lead to myocardial dysfunction in many cases, with an impairment in both contractility and relaxation. Hypotension is quite common, occurring in up to 65% of patients within 6 hours of ROSC,(5) and not surprisingly leads to a significant increase in mortality. Impaired left ventricular systolic function is observed in nearly half of survivors who become hypotensive, but also in nearly one-third of normotensive patients.(6)
The AHA guidelines recommend treating hypotension (systolic blood pressure < 90 mmHg) with an initial fluid bolus of 1-2 liters of crystalloid, though much larger volumes may be needed over the first 24 hours. Following crystalloid infusion, hypotension should be treated with IV vasopressors. Epinephrine, norepinephrine, and dopamine are all reasonable initial choices. Norepinephrine, which predominantly causes vasoconstriction via α1-agonist activity, seems a reasonable first choice. Given the high frequency of cardiac dysfunction associated with the post-arrest state, initiation of an agent with ß1 activity (epinephrine, dobutamine) should be considered either initially, or in response to continued hypotension following norepinephrine infusion. While studies have not established an optimal blood pressure following cardiac arrest, the guidelines note that a goal mean arterial pressure of 65 mmHg seems reasonable. Mechanical circulatory support, via intra-aortic balloon counterpulsation or placement of a left-ventricular assist device, can be considered in select cases of refractory hypotension, though there is little evidence that their use improves outcome.
Following cardiac arrest, many patients remain comatose and require invasive positive pressure ventilation. Vent settings must be considered carefully following ROSC, and must be adjusted based on the patient’s clinical condition. While it is important that oxygenation be maintained in the post-arrest period to promote aerobic metabolism, the deleterious effects of hyperoxia must be considered. Excess oxygen can lead to the increased production of oxygen free radicals, leading to lipid peroxidation and potentially resulting in worse neurologic outcomes. One large observational trial demonstrated increased mortality among patients with hyperoxia (PaO2 ≥ 300 mmHg) on arrival to the ICU, compared to both those with hypoxia (PaO2 < 60 mmHg) and those with a partial pressure of oxygen between 60 and 300 mmHg.(7) While it is reasonable to set a FiO2 of 100% initially following ROSC, it is important to monitor arterial oxygen content, and rapidly titrate the FiO2 to maintain an oxygen saturation of ≥ 94%.
Adequate ventilation is as important as adequate oxygenation. Patients are frequently acidotic following cardiac arrest, with a combined metabolic and respiratory etiology. A mean pH of 6.9 and mean PaCO2 of 78.3 were observed in one series of post-arrest patients.(8) Correction of this respiratory acidosis is critical, as persistent acidosis leads to both cardiac dysfunction and arterial vasodilation. There is often an impulse, therefore, to hyperventilate the post-arrest patient in order to compensate for the metabolic component of the acidosis. It is important, however, to consider the effect that PaCO2 has on cerebral perfusion. While cerebral blood flow increases with improvements in mean arterial pressure, it also falls with decreases in PaCO2. This occurs as a result of increasing cerebral vascular resistance, which varies inversely with PaCO2 (Figure 1). Therefore hyperventilation can lead to decreased cerebral blood flow, and theoretically worsen neurologic outcomes. Hyperventilation can also increase intra-thoracic pressure by prohibiting adequate time for exhalation between breaths. This increased pressure leads to decreased venous return to the heart, and therefore decreased cardiac output. For these reasons, the guidelines recommend that ventilation be titrated to generate a high-normal PaCO2 of 40-45 mmHg, or an end-tidal CO2 of 35-40 mmHg.
While not universally adopted, therapeutic hypothermia came into vogue after the publication of two trials in The New England Journal of Medicine in February of 2002. These two trials comprised a total of 350 patients randomized to either normothermia, or to a hypothermia protocol with a goal temperature of 33°C for 12 hours in the smaller study(9), and 32-34°C for 24 hours in the larger study.(10) Both studies demonstrated significant increases in both survival and favorable neurologic outcome. The AHA guidelines recommend cooling patients to a temperature of 32°C to 34°C for 12-24 hours following ROSC, based largely on the results of these two studies. However, these recommendations predate the release of the results of a much larger trial published last December, also in The New England Journal, that called these results into question.(11) In this study, 939 patients were randomized to hypothermia protocols with targeted temperatures of either 33°C or 36°C. No difference in survival or favorable neurologic outcome was observed, leading some to dismiss therapeutic hypothermia entirely.
The more likely explanation for this disparity is that the prevention of hyperthermia, rather than the degree of hypothermia, led to improved outcomes in the initial studies. In the larger 2002 study, a significant proportion of the “normothermia” patients were actually hyperthermic for a significant portion of the 48 hours following ROSC: over a quarter of these patients had temperatures above 38°C for the final 24 hours of this period. While not designed to show causality, at least one study has demonstrated an association between hyperthermia and poor neurologic outcomes.(12) The median highest temperature in those patients who survived with a good neurologic outcome was 37.7°C, compared to a median highest temperature of 38.3°C in those who died or had a poor neurologic outcome. While targeted temperature management is recommended, the optimal temperature remains uncertain, and the primary goal should be prevention of hyperthermia. It should be noted that targeted temperature management is recommended only for patients who remain comatose following ROSC.
Patients with ST-elevation myocardial infarction (STEMI) should receive aggressive care, with all attempts made to ensure reperfusion. While percutaneous coronary intervention (PCI) is considered front-line therapy, thrombolytics have been shown to be safe and effective following cardiac arrest,(13) and should be employed when PCI is not available. It should be noted that the combination of therapeutic hypothermia and thrombolysis has not been well-studied.
The use of cardiac catheterization following cardiac arrest in patients without STEMI is highly dependent on both location and availability. In the Parisian healthcare system, all patients successfully resuscitated from OHCA without a clear non-cardiac cause are transported immediately for coronary angiography, regardless of ECG findings. Data from this region indicate that significant coronary stenosis is present in around 60% of patients following cardiac arrest(14,15). However, only about one quarter of these patients undergo PCI. While successful PCI has been shown to correlate with improved survival among these patients, this does not provide evidence of benefit from routine catheterization, as there is no control group for comparison.
A single controlled, observational study of patients resuscitated from arrest due to ventricular dysrhythmias has demonstrated an overall survival benefit with early catheterization (survival of 65.6% vs. 48.6%).(16) However, among those who underwent catheterization, successful PCI itself was not associated with improvement in survival rates, suggesting that factors other than catheterization were responsible for the improved mortality. As this was not a randomized trial, it is likely that patients suspected of having a better prognosis may have been referred for catheterization, whereas those in whom aggressive care was felt to be futile would be treated more conservatively. While there is little evidence to support routine cardiac catheterization, the guidelines state that “consideration of emergent coronary angiography may be reasonable even in the absence of STEMI,” and such consideration should be given when the suspicion for acute coronary syndrome (ACS) is high.
Given the pro-inflammatory state associated with survivors of cardiac arrest, some have proposed the use of corticosteroids in this patient population. The guidelines note a paucity of evidence in this regard, and make no recommendation either for, or against, their use. In July of 2013, a study was reported out of Greece in which patients were randomized to either standard care, or to receive a combination of vasopressin, steroids, and epinephrine during arrest, followed by high-dose steroids following ROSC.(17) This methodologically rigorous randomized, blinded trial revealed a nearly 3-fold increase in neurologically favorable survival among patients receiving the intervention compared to controls (13.9% vs. 5.1%). Two primary barriers to implementation of this protocol remain: first, this trial included only patients suffering in-hospital cardiac arrest, and the protocol has not been studied in OHCA patients; second, the results of this trial have not been validated in cohorts outside of this single healthcare system. For these reasons, few institutions have adopted this intervention, and its use in OHCA cannot yet be recommended.
Care of the post-cardiac arrest patient requires careful attention to an ever-changing clinical condition. Given the increasing prevalence of ED boarding, much of the initial phase of post-arrest care is now conducted in the ED, and emergency physicians should be familiar with the latest evidence and guidelines. Optimization of tissue oxygen delivery (while avoiding hyperoxia), prevention of hyperthermia, and an aggressive search for the underlying cause of the arrest should be our greatest priorities. While these strategies do not ensure long-term neurologic recovery, they remain our best treatment strategies in this devastating condition.
Dr. Cohn is an Assistant Professor of Emergency Medicine at Washington University in St. Louis where he is the residency Journal Club director. He is also the voice of the EMJClub podcast.
- McNally B, Robb R, Mehta M, et al; Centers for Disease Control and Prevention. Out-of-hospital cardiac arrest surveillance — Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005–December 31, 2010. MMWR Surveill Summ. 2011 Jul 29;60(8):1-19.
- 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.
- Peberdy MA, Callaway CW, Neumar RW, et al; American Heart Association. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010 Nov 2;122(18 Suppl 3):S768-86.
- Salciccioli JD, Cocchi MN, Rittenberger JC, et al. Continuous neuromuscular blockade is associated with decreased mortality in post-cardiac arrest patients. Resuscitation. 2013 Dec;84(12):1728-33.
- Kilgannon JH, Roberts BW, Reihl LR, et al. Early arterial hypotension is common in the post-cardiac arrest syndrome and associated with increased in-hospital mortality. Resuscitation. 2008 Dec;79(3):410-6.
- Laurent I, Monchi M, Chiche JD, et al. Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest. J Am Coll Cardiol. 2002 Dec 18;40(12):2110-6.
- Kilgannon JH, Jones AE, Shapiro NI, et al; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Association between arterial hyperoxia following resuscitation from cardiac arrest and in-hospital mortality. JAMA. 2010 Jun 2;303(21):2165-71.
- Makino J, Uchino S, Morimatsu H, et al. A quantitative analysis of the acidosis of cardiac arrest: a prospective observational study. Crit Care. 2005 Aug;9(4):R357-62.
- Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002 Feb 21;346(8):557-63.
- Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002 Feb 21;346(8):549-56. Erratum in: N Engl J Med 2002 May 30;346(22):1756.
- Nielsen N, Wetterslev J, Cronberg T, et al; TTM Trial Investigators. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013 Dec 5;369(23):2197-206.
- Zeiner A, Holzer M, Sterz F, et al. Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome. Arch Intern Med. 2001 Sep 10;161(16):2007-12.
- Voipio V, Kuisma M, Alaspaa A, et al. Thrombolytic treatment of acute myocardial infarction after out-of-hospital cardiac arrest. Resuscitation. 2001;49:251–258.
- Chelly J, Mongardon N, Dumas F, et al. Benefit of an early and systematic imaging procedure after cardiac arrest: insights from the PROCAT (Parisian Region Out of Hospital Cardiac Arrest) registry. Resuscitation. 2012 Dec;83(12):1444-50.
- Dumas F, Cariou A, Manzo-Silberman S, et al. Immediate percutaneous coronary intervention is associated with better survival after out-of-hospital cardiac arrest: insights from the PROCAT (Parisian Region Out of hospital Cardiac ArresT) registry. Circ Cardiovasc Interv. 2010 Jun 1;3(3):200-7.
- Hollenbeck RD, McPherson JA, Mooney MR, et al. Early cardiac catheterization is associated with improved survival in comatose survivors of cardiac arrest without STEMI. Resuscitation. 2013 Aug 6.
- Mentzelopoulos SD, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013 Jul 17;310(3):270-9.