What Drip to Use After the Drop - Post-Cardiac Arrest Hypotension

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Bougouin W, Slimani K, Renaudier M, et al. Epinephrine versus norepinephrine in cardiac arrest patients with post-resuscitation shock. Intens Care Med 2022;48(3):300–10. 10.1007/s00134-021-06608-7

Introduction 

During a cardiac arrest resuscitation, finally palpating a pulsatile flow beneath your gloved fingertips brings a sense of satisfaction like no other. But just as you go to finally breathe a sigh of relief and wipe the beading sweat off your brow, your now widening pupils focus on the patient’s steadily plummeting blood pressure. As you begin to sense your own heart palpitating, you think about medications to utilize in hopes of staving off another round of chest compressions. Since you’ve already given four doses of code-dose epinephrine, maybe an epinephrine infusion is best? You also recall that norepinephrine seems to be a popular choice in patients with shock, so maybe you should start that instead? 

Unfortunately, this is all too common dilemma for providers, as 50-75% of patients will experience shock following a successful cardiac arrest resuscitation.(1) Furthermore, the pathophysiology of post-cardiac arrest syndrome is complicated. It not only involves arrest-related myocardial dysfunction, but also a closely associated reperfusion injury and a subsequent systemic inflammatory response similar to that seen in patients with sepsis.(2) Therefore, it’s logical to wonder if providers should avoid administering additional pro-arrhythmogenic agents, and instead shift focus to address the post-ROSC vasoplegia with other agents instead. In a study published in Intensive Care Medicine in 2022, Bougouin and colleagues set out to answer this question.(3) Specifically, they compared the association of epinephrine versus norepinephrine use with outcomes of patients admitted to the ICU with post-resuscitation shock, following a successfully resuscitated out-of-hospital cardiac arrest.  

Design 

  • Retrospective multicenter observational study  

  • Primary outcome was all-cause mortality 

  • Secondary outcomes focused on:  

    • Neurological status at discharge defined using Cerebral Performance Category (CPC) scores 

    • Cardiovascular-specific mortality defined as occurrence of recurrent cardiac arrest or presence of refractory shock  

Subjects 

  • Total of 766 patients 

    • Utilized the Sudden Death Expertise Center registry in France 

    • Patients from five large university hospitals 

  • All of whom needed vasopressors following ROSC for more than 6 hours, despite receiving adequate fluids 

  • Exclusion criteria 

    • Obvious extra-cardiac cause of cardiac arrest such as trauma, drowning, drug overdose, electrocution, or asphyxia due to an external cause 

    • Refractory cardiac arrest without ROSC 

    • Refractory shock requiring ECMO  

    • Continuous treatment with both epinephrine and norepinephrine 

Results 

  • Of the 766 patients, 63% received norepinephrine and the remaining 37% received epinephrine  

  • Overall, about 1/3 of patients survived to hospital discharge 

  • Primary outcomes: 

    • Patients receiving the epinephrine infusion had a higher all-cause mortality during their hospital stay: 

      • 83% compared to 61% mortality rate in the norepinephrine infusion group (p<0.001) 

    • Even after adjusting for specific factors that are known to affect out-of-hospital arrest outcomes, epinephrine administration was independently associated with all-cause mortality: 

      • Logistic regression adjusted for sex, age, bystander CPR, initial shockable rhythm, time to CPR, time to ROSC, initial pH, etc.  

      • OR 2.6, 95%CI 1.4–4.7, p=0.002 

  • Secondary outcomes: 

    • Epinephrine group had more deaths from cardiovascular-specific mortality: 

      • 44% compared to 11% mortality rate in the norepinephrine infusion group (p<0.001) 

      • includes higher rates of death from refractory shock in the epinephrine group (35% vs. 9%, p<0.001) 

      • more deaths from recurrent cardiac arrest in the epinephrine group (9% vs. 3%, p<0.001) 

    • Epinephrine group had a lower frequency of favorable neurologic outcomes: 

      • defined as CPC scores of 3-5 

      • 15% compared to 37% in those treated with norepinephrine (p<0.001) 

Limitations 

  • The group of patients receiving the epinephrine infusion seemed to be sicker at baseline 

    • Epinephrine group had a longer mean time to ROSC 

      • 25 vs 20 minutes in the norepinephrine group (p<0.001) 

    •  Epinephrine group had lower incidence of an initial shockable rhythm 

      • 44% compared to 57% in the norepinephrine group (p<0.001) 

    • Epinephrine group also had higher lactate levels (7.6 vs 4.8, p<0.001), lower arterial pH (7.17 vs 7.23, p<0.001), and lower mean arterial blood pressure (86 vs 89mmHg, p=0.03) at admission  

  • The authors did acknowledge these differences between the two groups and performed propensity scoring analysis to adjust for confounders  

    • After adjustment on the propensity score, epinephrine infusion was still associated with higher overall mortality (OR 2.1, 95%CI 1.1–4.0, p=0.02) and cardiovascular-specific mortality (aOR 4.3, 95%CI 2.2–8.3, p<0.001) 

Discussion 

This was a large cohort study that found an increase in all-cause mortality, as well as cardiovascular-specific mortality and poorer neurological outcomes, amongst post-ROSC patients receiving an epinephrine infusion for post-resuscitation shock. Physiologically, this can likely be explained by the pro-arrhythmogenic properties of a beta-adrenergic medication acting on a stunned myocardium. Furthermore, the alpha-adrenergic properties of norepinephrine likely mitigate the sepsis-like vasoplegic state seen in the post-ROSC period, without irritating the already dysfunctional heart tissue. Nonetheless, it is difficult to generalize these results to US population where survival of OHCA to hospital discharge is approximately 7%, compared to 30% reported in this European study.(4) Furthermore, despite the propensity analysis, it is difficult to ignore the glaring characteristic differences between the epinephrine and norepinephrine groups and question the presence of underlying confounders. Overall, this study certainly makes one think twice before reflexively reaching for an epinephrine infusion in a patient who recently achieved ROSC and is now exhibiting signs of shock. Yet more definitive data, and especially a randomized control trial, is needed before this ongoing debate is settled. Until then, clinicians will likely continue to rely on the clinical data available to them, including vital signs, EKG, and bedside ultrasound, when choosing the ideal vasopressor for combating post-ROSC shock. 

References  

  1. Jozwiak M, Bougouin W, Geri G, Grimaldi D, Cariou A. Post-resuscitation shock: Recent advances in pathophysiology and treatment. Annals of Intensive Care. 2020;10(1):170. 

  2. Stub D, Bernard S, Duffy SJ, Kaye DM. Post cardiac arrest syndrome. Circulation. 2011;123(13):1428-1435. 

  3. Bougouin W, Slimani K, Renaudier M, et al. Epinephrine versus norepinephrine in cardiac arrest patients with post-resuscitation shock. Intensive Care Med. 2022;48(3):300-310. 

  4. 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;3(1):63-81. 

Authorship

  • Written by - Max Kletsel, MD, PGY-3 University of Cincinnati Department of Emergency Medicine

  • Peer Review, Editing, Posting - Jeffery Hill, MD MEd, Associate Professor, University of Cincinnati Department of Emergency Medicine

Cite As

Kletsel, M. Hill, J. (November 18, 2022) What Drip to Use After the Drop - Post-Cardiac Arrest Hypotension. TamingtheSRU. https://www.tamingthesru.com/blog/journal-club/what-drip-to-use-after-the-drop