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Date: May 7th, 2021

Guest Skeptic: Dr. Ryan Stanton is a community emergency physician with Central Emergency Physicians in Lexington, KY. He is on the Board of Directors for the American College of Emergency Physicians and host of the ACEP Frontline Podcast. He is an EMS medical director with Lexington Fire/EMS as well as the AMR/NASCAR Safety Team.

Reference: Shah and Mitra. Use of Corticosteroids in Cardiac Arrest – A Systematic Review and Meta-Analysis. Crit Care Med Feb 2021

Case: A 58-year-old male has a witnessed cardiac arrest while admitted to the observation unit for a chest pain evaluation. CPR is initiated and a hospital rapid response team is called. The resuscitation team arrives and ACLS protocols are continued. The issue of whether corticosteroids should be administered is brought up during the code.

Background: Cardiac arrests have  high morbidity and mortality rates both in-hospital cardiac arrests (IHCAs) and out of hospital cardiac arrests (OHCAs). It is estimated that the survival to discharge for an IHCA is approximately 18% with only 10% for OHCAs.

This contrasts with what the public sees watching CPR being done on TV. Survival on screen is four to five times higher than reality, according to one study (see graphic).

Improving outcomes for patients with cardiac arrests has been an ongoing challenge in pre-hospital and in hospital medicine. We have discussed many aspects of such care on the SGEM including:

We understand more physiologic changes that take place following cardiac arrest and there have been several studies looking at the potential role of corticosteroids in the intra-arrest timeframe. SGEM#50 looked at a RCT published in JAMA 2013 looking to see if a vasopressin, steroids, and epinephrine (VSE) protocol for IHCAs could improve survival with favorable neurologic outcome compared to epinephrine alone.

That RCT had 268 patients and demonstrated a better odds ratio for ROSC and survival to discharge with good neurologic outcome. The SGEM bottom line at the time was that the results were very interesting, but a validation study should be done to try and replicate the results. I have not seen a validation study published.

We know that epinephrine can increase ROSC, survival to hospital, and even survival to hospital discharge based on the Paramedic 2 Trial. Unfortunately, epinephrine was not superior to placebo for the patient-oriented outcome of survival with good neurologic outcome.

Corticosteroids have been suggested as a possible therapy in these clinical situations. However, there is an old RCT that looked at dexamethasone in OHCA and it failed to demonstrate an improvement in survival to hospital discharge (Paris et al AEM 1984). A SRMA published in 2020 on the use of steroids after cardiac arrest reported an increase in ROSC and survival to discharge but was limited by the availability of adequately powered high-quality RCTs (Liu et al JIMR 2020).

Clinical Question: Does the use of corticosteroids impact neurologic outcomes and mortality in patients with a cardiac arrest?

Reference: Shah and Mitra. Use of Corticosteroids in Cardiac Arrest – A Systematic Review and Meta-Analysis. Crit Care Med Feb 2021

  • Population: Randomized controlled trials and comparative observational studies of patients with in or out of hospital cardiac arrests
    • Exclusions: Any single arm studies, case reports/ series, narrative reviews, and studies irrelevant to the focus of this article.
  • Intervention: Corticosteroids as adjunct therapy in cardiac arrest
  • Comparison: Patients that did not receive corticosteroids in cardiac arrest
  • Outcome:
    • Primary Outcomes: Good neurologic outcome (measured using the Glasgow-Pittsburgh Cerebral Performance Category score), survival to hospital discharge, and survival at greater than or equal to 1 year
    • Secondary Outcomes: Return of spontaneous circulation (ROSC), Intensive Care Unit (ICU) and hospital length of stay (LOS), duration of vasopressor and inotropic treatment, and blood pressure (systolic blood pressure, diastolic blood pressure, and mean arterial pressure [MAP]) during CPR and after ROSC.

Authors’ Conclusions: “The study found that there are limited high-quality data to analyze the association between corticosteroids and reducing mortality in cardiac arrest, but the available data do support future randomized controlled trials. They did find that corticosteroids given as part of a vasopressin, steroids, and epinephrine regimen in in-hospital cardiac arrest patients and for post resuscitation shock did improve neurologic outcomes, survival to hospital discharge, and surrogate outcomes that include return of spontaneous circulation and hemodynamics. They found no benefit in in-hospital cardiac arrest or out-of-hospital cardiac arrest patients receiving corticosteroids only; however, a difference cannot be ruled out due to imprecision and lack of available data.”

Quality Checklist for Therapeutic Systematic Reviews:

  1. The clinical question is sensible and answerable. Yes
  2. The search for studies was detailed and exhaustive. Yes
  3. The primary studies were of high methodological quality. No
  4. The assessment of studies were reproducible. Yes
  5. The outcomes were clinically relevant. Yes
  6. There was low statistical heterogeneity for the primary outcomes. No
  7. The treatment effect was large enough and precise enough to be clinically significant. No

Results: Seven studies were included in this SRMA (5 RCTs and 2 observational studies). Total cohort was 6,199 with 90% coming from one retrospective study from Taiwan.

Key Result: Statistical difference in good neurologic outcome and survival to hospital discharge with steroids but not survival at 1 year or longer.

  • Primary Outcomes: 
    • Good neurologic outcome: 4 RCTs RR 2.85 (95% CI; 1.39-5.84)
    • Survival to hospital discharge: 4 RCTs RR 2.58 (95% CI; 1.36-4.91)
    • Survival at greater than or equal to 1 year: 1 RCT RR 2.34 (95% CI; 0.83–6.54)
  • Secondary Outcomes:
    • ROSC: 4 RCTs RR 1.32 (95% CI; 1.16–1.50)
    • ICU and Hospital LOS: 1 RCT No statistical difference
    • Duration of vasopressor and inotropic treatment: No studies
    • Hemodynamic: 2 studies in supplemental material
    • Safety: 3 studies with no statistical differences

1. Few Studies – Despite cardiac arrest being a common event with high morbidity and mortality only five RCTs with a total of 530 patients could be found searching the world’s literature on this topic that met the inclusion and exclusion criteria. You would think that there would be much more data to help inform our care.

2. High Risk of Bias – Of the five trials that they could find to include only four could be assessed for bias using the Cochrane Risk of Bias Assessment 2 Tool. Three out of the four were at high-risk of bias. This further threatens the validity of the findings and the strength of the conclusions that can be drawn.

3. Single Research Group – When you drill down into this SRMA you find that 92% of the RCT data for IHCA comes from two trials by the same author group in Greece. One trial was published in 2008 and the other in 2013. This can raise the issue of external validity to other healthcare systems in 2021.

4. VSE Protocol – We can drill down even farther into the data and say that the largest RCT (n=268) was the multi-centered trial from Greece. This is the trial we reviewed on SGEM#50 that used vasopressin, steroids, and epinephrine not steroids alone. In addition, it was only for IHCA not for OHCA. So, we don’t have any RCTs to answer the question of whether steroid alone used during cardiac arrest (IHCA or OHCA) result in an improved patient-oriented outcome (POO).

5. Reproducibility Crisis – Nature published a survey by Baker in 2016 asking more than 1,500 scientists if there was a reproducibility crisis in science and 90% said yes and only 3% said no. The Greek study from 2013 has not been replicated in over eight years as far as we know. There are too many examples of one and done in medicine. Think of tPA for stroke. There is only one placebo-controlled trial in <3hours (NINDS-I 1995) that claims efficacy for its primary outcome and only one in 3-4.5hrs (ECASS-III 2008). Neither of these trials has been replicated and look at the debates were are still having due to a lack of high-quality evidence.

Comment on Authors’ Conclusion Compared to SGEM Conclusion:  Overall, we agree with the findings of the authors and feel they made a realistic evaluation and conclusions, based on the available data.

SGEM Bottom Line: We have no evidence to support the use of corticosteroid in OHCA and only very weak evidence for corticosteroids in IHCA as part of a VSE protocol.

Case Resolution: ROSC is achieved, and the patient is transferred to the ICU. The patient eventually went to the cath lab where an LAD stent was placed. Resuscitation care included targeted temperature management and a newly established VSE protocol. The patient full-recovered and was discharged home a few days later to continue cardiac rehab.

Clinical Application: Physicians will have different levels of evidence to adopt a new treatment into their clinical practice. It would be reasonable to consider using corticosteroids as part of a VSE protocol in patients with IHCA but certainly should not be mandated or made into a quality metric.  This is because we only have one relatively small RCT from Greece that was of low risk of bias but has never been replicated.

What Do I Tell the  Patient? Your loved one experienced cardiac arrest. We got his heart going again and he is doing better. Our hospital has a protocol that gives three medicines we hope will help him pull through in good condition. He is being admitted ot the ICU. The heart doctors plan to take him to cath lab soon see if he has a blockage in his heart that cause it to stop.

Keener Kontest: Last weeks’ winner was Arne Jensen a Paramedic from Denmark. He knew droperidol was discovered by Janssen Pharmaceutica.

Listen to the podcast this week to hear the trivia question. Email your answer to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.