The Case

A 54-year-old man is admitted to the observation unit to rule out an acute coronary syndrome. While waiting for further testing, he has a cardiac arrest, and a code blue is called. CPR and advanced cardiac life support protocols are initiated. The resident asks if we should be administering corticosteroids because of an old trial she remembers reading.

Clinical Question

Is there better survival with a good neurological outcome in patients with cardiac arrest who are treated with corticosteroids?

Background

There are high morbidity and mortality rates with both in-hospital cardiac arrests (IHCAs) and out-of-hospital cardiac arrests (OHCAs). Improving outcomes for patients with cardiac arrest has been challenging. Various treatment modalities, such as therapeutic hypothermia, intravenous versus intraosseous access, supraglottic airways, crowdsourcing CPR, and mechanical CPR, have been tried with mixed results.^1–6

A randomized controlled trial (RCT) published in 2013 investigated a protocol of vasopressin, steroids, and epinephrine (VSE) for IHCAs.⁷ It reported a better odds ratio for return of spontaneous circulation (ROSC) and survival to discharge, with good neurological outcome with the protocol. This was an interesting finding, but a validation study replicating the results has apparently not been published.

An older RCT looked at the role of the corticosteroid dexamethasone in OHCA.⁸ That trial failed to demonstrate improvement in survival to hospital discharge. Liu et al performed a systematic review and meta-analysis on the use of corticosteroids after cardiac arrest.⁹ They found there was an increase in ROSC and survival to discharge but were limited by the availability of adequately powered high-quality RCTs.

Reference: Shah K, Mitra AR. Use of corticosteroids in cardiac arrest-a systematic review and meta-analysis. Crit Care Med. 2021;49(6):e642-e650.

• Population: RCTs and observational studies of patients with IHCA or OHCA
  • Exclusions: 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 who did not receive corticosteroids in cardiac arrest
• Outcomes:
  • Primary Outcomes: Good neurological outcome (measured using the Glasgow-Pittsburgh Cerebral Performance Category score), survival to hospital discharge, and survival at equal to or greater than one year
  • Secondary Outcomes: ROSC, ICU and hospital length of stay (LOS), duration of vasopressor and inotropic treatment, and blood pressure including mean arterial pressure during CPR and after ROSC

Authors’ Conclusions

“Our 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. We did find that corticosteroids given as part of a vasopressin, steroids, and epinephrine regimen in in-hospital cardiac arrest patients and for postresuscitation shock did improve neurologic outcomes, survival to hospital discharge, and surrogate outcomes that include return of spontaneous circulation and hemodynamics. We 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.”

Results

There were five RCTs and two observational studies included in this systematic review and meta-analysis (see Table 1). The total cohort consisted of 6,199 patients with a cardiac arrest (90 percent of the cohort came from one retrospective observational study conducted in Taiwan).

• Secondary Outcomes:
  • ROSC: Four RCTs, relative risk 1.32 (95% CI, 1.16–1.50)
  • ICU and hospital LOS: One RCT, no statistical difference
  • Duration of vasopressor and inotropic treatment: No studies
  • Hemodynamic: Two studies in supplemental material
  • Safety: Three studies with no statistical differences

Table 1: Trial Characteristics

Evidence-Based Medicine Commentary

1. Few Studies: There were only five RCTs with a total of 530 patients included in this systematic review and meta-analysis, despite cardiac arrest being a common event with high morbidity and mortality.
2. High Risk of Bias: Only four of the five RCTs could be assessed for bias using the Cochrane Risk of Bias Assessment 2 Tool. Three of those four were at high risk of bias. The lack of high-quality studies weakens any conclusions that can be drawn from these data.
3. Single Research Group: The vast majority of the RCT data for IHCA (92 percent) came from two trials by the same group of authors in Greece. One trial was published in 2008 and the other in 2013. This raises the issue of external validity to 2021 and other health care systems.
4. VSE Protocol: The largest RCT (n=268) assessing corticosteroids for cardiac arrest was part of a VSE protocol for IHCA. The protocol included vasopressin, corticosteroids, and epinephrine rather than corticosteroids alone. This means there has not yet been an RCT that addresses corticosteroids alone for IHCA, though equipoise would be difficult to justify in many care settings. The one RCT for OHCA was from 1984 and failed to show a patient-oriented benefit for dexamethasone when given in addition to standard American Heart Association protocols.
5. Replication: The RCT from Greece assessing VSE in IHCA has, to my knowledge, not been replicated. The lack of replication is a common problem in science.¹⁰

Bottom Line

There is weak direct evidence to support the use of corticosteroids in IHCA as part of a VSE protocol and no evidence to support the use in OHCA.

Case Resolution

ROSC is achieved, and the patient is transferred to the ICU. The patient eventually goes for an angiogram where a stent is place in his left anterior descending coronary artery. The patient makes a full recovery and is discharged home within a week. You decide to do a journal club with your EM residents to discuss the use of corticosteroids for IHCAs and consider whether your hospital should add a VSE protocol.

Thank you to Dr. Ryan Stanton, who is a community emergency physician with Central Emergency Physicians in Lexington, Kentucky, a member of the ACEP Board of Directors, and host of the ACEP Frontline Podcast.

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

References

1. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369(23):2197-2206.
2. Kawano T, Grunau B, Scheuermeyer FX, et al. Intraosseous vascular access is associated with lower survival and neurologic recovery among patients with out-of-hospital cardiac arrest. Ann Emerg Med. 2018;71(5):588-596.
3. Benger JR, Kirby K, Black S, et al. Effect of a strategy of a supraglottic airway device vs tracheal intubation during out-of-hospital cardiac arrest on functional outcome: the AIRWAYS-2 randomized clinical trial. JAMA. 2018;320(8):779-791.
4. Wang HE, Schmicker RH, Daya MR, et al. Effect of a strategy of initial laryngeal tube insertion vs endotracheal intubation on 72-hour survival in adults with out-of-hospital cardiac arrest: a randomized clinical trial. JAMA. 2018;320(8):769-778.
5. Derkenne C, Jost D, Roquet F, et al. Mobile smartphone technology is associated with out-of-hospital cardiac arrest survival improvement: the first year “Greater Paris Fire Brigade” experience. Acad Emerg Med. 2020;27(10):951-962.
6. Gates S, Quinn T, Deakin CD, et al. Mechanical chest compression for out of hospital cardiac arrest: systematic review and meta-analysis. Resuscitation. 2015;94:91-97.
7. 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;310(3):270-279.
8. Paris PM, Stewart RD, Deggler F. Prehospital use of dexamethasone in pulseless idioventricular rhythm. Ann Emerg Med. 1984;13(11):1008-1010.
9. Liu B, Zhang Q, Li C. Steroid use after cardiac arrest is associated with favourable outcomes: a systematic review and meta-analysis. J Int Med Res. 2020;48(5):300060520921670.
10. Baker M. 1,500 scientists lift the lid on reproducibility. Nature. 2016;533(7604):452-454.