Washington University Emergency Medicine Journal Club
Determinants of Outcome in Cardiac Arrest – May 2020
You are working a busy shift in TCC when you get a page: cardiac arrest to 4 right, ETA 6 minutes. The paramedics arrive with an approximately 60 year-old-man with unknown past medical history who experienced a witnessed out-of-hospital cardiac arrest (OHCA). He received bystander CPR and 3 doses of epinephrine per EMS. He was initially in ventricular tachycardia and was defibrillated. Ever since that initial rhythm he has been in PEA. The patient is hooked up to the monitors and excellent CPR with minimal interruptions is initiated.
After two more rounds of epinephrine the patient obtains ROSC. His total down time was 42 minutes. A 12-lead ECG is obtained which shows an anterolateral STEMI. He is taken to the cardiac catheterization lab and then admitted to the ICU for further management.
You move on about your shift seeing the remainder of your patients with an accomplished feeling that you have “saved another life”. You decide to look up the patient for a follow-up 2 months later and note that his hospital course included minimal return of neurological function, tracheostomy, gastrostomy tube placement, and discharge to a long term care facility. You think to yourself… Is there something we could have done to improve this patient’s chance at a better neurological outcome?
Not applicable for this review.
Articles were selected by the Critical Care attending and his residents. No formal search strategy was performed.
Article 1: Goto Y, Funada A, Goto Y. Relationship between the duration of cardiopulmonary resuscitation and favorable neurological outcomes after out-of-hospital cardiac arrest: a prospective, nationwide, population-based cohort study. J Am Heart Assoc, 2016 Mar 18;5(3):e002819. Answer Key.
Article 2: Tanaka H, Takyu H, Sagisaka R, et al. Favorable neurological outcomes by early epinephrine administration within 19 minutes after EMS call for out-of hospital cardiac arrest patients. Am J Emerg Med. 2016;34(12):2284-2290. Answer Key.
Article 3: Youn CS, Park KN, Kim SH, et al. The Cumulative Partial Pressure of Arterial Oxygen Is Associated With Neurological Outcomes After Cardiac Arrest Treated With Targeted Temperature Management. Crit Care Med. 2018;46(4):e279- e285. Answer Key.
Article 4: Holmberg MJ, Issa MS, Moskowitz A, et al. Vasopressors during adult cardiac arrest: A systematic review and meta-analysis. Resuscitation. 2019;139:106-121. Answer Key.
Brief Bottom Line
In this review we sought to understand some of the factors influencing outcomes in out of hospital cardiac arrest (OHCA), including hyperoxia and the now controversial use of epinephrine and other vasopressors, and to evaluate the association between duration of CPR and potential for survival.
Consistent with prior reports demonstrating poor outcomes associated with hyperoxia for stroke and sepsis, we reviewed a retrospective study that demonstrated a decreased odds of having a favorable neurologic outcome at 6 months with increasing cumulative PaO2 levels in the 24 hours following cardiac arrest. After adjusting for known confounders, increasing 24-hour cumulative PaO2 cutoffs were associated with increasing odds ratios for poor neurologic outcome, achieving statistical significance at cutoffs of 200 (OR 1.659, 95% CI 1.194-2.305), 250 (OR 2.082, 95% CI 1.204–3.600), and 300 mmHg (OR 3.969, 95% CI 1.450-10.862). This study was limited by its retrospective nature necessitating logistic regression to account for known confounders, but no means of accounting for unknown confounders. Despite its limitations, and in the context of previous evidence, it seems prudent to titrate supplemental oxygen downward following cardiac arrest to maintain normal oxygen saturation and PaO2 levels.
Goto et al undertook a study in Japan to determine the duration of prehospital CPR that would allow cessation of resuscitative efforts without sacrificing survivorship or favorable neurologic outcomes. Using data from a large, nationwide database, they found (not surprisingly) an inverse relationship between CPR duration and good outcomes, such that every additional minute of CPR time was associated with an decreased odds ratio for 1-month survival of 0.95 (95% CI: 0.95–0.96) and a decreased OR for a favorable 1-month neurological outcome of 0.95 (95% CI: 0.94– 0.95). To achieve a cumulative proportion of >99% of favorable neurologic outcomes at one month, CPR durations of 35 minutes for all patients, 35 minutes for PEA and ventricular fibrillation/pulseless ventricular tachycardia, and 42 minutes for asystole were required. While interesting, it remains unclear whether these time- frames should or could be used to terminate resuscitative efforts in prehospital cardiac arrest, and care should be taken before generalizing these results given issues with external validity.
Given controversies with the use of epinephrine in cardiac arrest, two papers regarding its use were reviewed. The first (Tanaka 2016) looked specifically at the timing of epinephrine administration and effects on outcomes. This retrospective observational study used data from a large, nationwide Japanese database of OHCA cases, and found that those patients who received epinephrine were more likely to have return of spontaneous circulation (ROSC) than those who did not (RR 1.92, 95% CI 1.85 to 1.99) but were less likely to have a favorable neurologic outcome at one month (RR 0.56, 95% CI 0.52 to 0.61). When epinephrine was given, there was a notable decline in rates of ROSC and favorable neurologic outcome with increasing time to administration of the first dose.
Based on prior conflicting reports, and specifically given the recent publication of the PARAMEDIC-2 trial (a large randomized controlled trial suggesting epinephrine did not improve rates of favorable neurologic outcome in OHCA), the International Liaison Committee on Resuscitation (ILCOR) commissioned a systematic review and meta-analysis looking at the use of vasopressors during cardiac arrest. This review found an increased rate of ROSC with epinephrine compared to placebo, but no benefit with regards to survival to hospital discharge with a favorable neurologic outcome (RR 1.21, 95% CI 0.90-1.62) or favorable neurologic outcome at 3 months (RR 1.30, 95% CI 0.94-1.80). Additionally, they found no difference in outcomes comparing vasopressin to epinephrine and no benefit to giving vasopressin in addition to epinephrine.