Postarrest Steroid Use May Improve Outcomes of Cardiac Arrest Survivors

Min-Shan Tsai, MD, PhD; Po-Ya Chuang, MHA; Chien-Hua Huang, MD, PhD; Chao-Hsiun Tang, PhD; Ping-Hsun Yu, MD; Wei-Tien Chang, MD, PhD; Wen-Jone Chen, MD, PhD


Crit Care Med. 2019;47(2):167-175. 

In This Article


The current study evaluated the association between steroids administered during postcardiac arrest care and the outcomes of cardiac arrest survivors by analyzing data from the NHIRD. The NHIRD showed that 22,768 patients had been successfully resuscitated from nontraumatic cardiac arrest during acute hospital care from 2004 to 2011. Our findings demonstrate that steroid use after ROSC may benefit survival to hospital discharge and 1-year survival. To our best knowledge, this study is the first to use nationwide population-based data to assess the independent association between steroid administered during the postcardiac arrest period and the outcomes of cardiac arrest survivors.

The postcardiac arrest syndrome may profit from glucocorticoid administered after ROSC in several aspects in addition to adrenal insufficiency. Glucocorticoids have been reported to decrease oxidative stress,[23] reduce apoptosis,[24] and thus ameliorate postresuscitation myocardial dysfunction[25] and cerebral injury.[26] Glucocorticoid administration following cardiac arrest also attenuates circulating cytokine levels[27] and leukocyte adhesion[28] and ameliorates endotoxin-mediated myocardial dysfunction and hemodynamic instability.[29] Furthermore, glucocorticoids also help to maintain cardiovascular stability by inhibiting catecholamine reuptake, enhancing vascular response to vasopressors[11,30] and decreasing nitric oxide-mediated vasodilation.[31]

However, the question of whether glucocorticoid use during the postcardiac arrest period is beneficial to cardiac arrest survivors has been debated for years. Jastremski et al[12] found that steroid use within 8 hours after ROSC did not improve survival or neurologic recovery in a retrospective study. However, that study was limited by differences in the etiology of cardiac arrest and underlying characteristics between the study groups that potentially favored the nonsteroid group. In another nonrandomized retrospective study of 458 OHCA survivors, no significant differences in survival or neurologic recovery between patients with and without steroid use were identified.[13] Donnino et al[14] conducted a randomized, double-blind, placebo-controlled trial, and found that hydrocortisone did not improve the time to shock reversal or clinical outcomes in patients with refractory shock following cardiac arrest. However, there were only 25 patients in each group, and the timing of first steroid dose was not restricted, which raised the question of whether a therapeutic window may exist. In contrast, two prospective, randomized, double-blind, placebo-controlled, parallel-group trials showed that combination therapy with vasopressors and methylprednisolone during CPR, followed by hydrocortisone after ROSC, improved neurologic outcomes, and the rate of survival to hospital discharge. As previously mentioned, multiple interventions given at the same time and obvious differences in ROSC rates between patient groups make it difficult to identify the isolated benefit of steroid administration after ROSC.[10,11] Different from the limitation of small patient numbers and design features in these clinical studies, the current study investigated the association between postarrest steroid use and outcome of cardiac arrest survivors by analyzing nationwide population-based data. To avoid the influence of steroid use during CPR in the current study, the patients who received steroid during resuscitation were excluded. Also, the variable "steroid use within 1 year prior to cardiac arrest" was matched to attenuate potential observational bias generated by steroid dependence prior to cardiac arrest. Furthermore, after reassessing the effect of postarrest steroid administration in patients with and without steroid use prior to cardiac arrest, all the results showed a consistent benefit of steroids.

In the current study, the dose analysis demonstrated a benefit of steroid administration only on the outcomes of patients who received a low dose of steroid, and this beneficial effect was reversed in patients who received a high dose of steroid. Higher steroid doses were associated with worse outcomes as compared with the nonsteroid group. Some possible reasons for this observation are: 1) steroid usage in some patients with a poor clinical recovery should not be rapidly tapered, 2) some patients in the high steroid group died too soon to be able to taper their steroid use, and 3) increasing steroid dose was associated with decreasing cardiovascular comorbidity burden (CAD, congestive heart failure, CKD) and increasing pulmonary comorbidity burden (COPD and asthma) potentially leading to important confounding in this analysis. Further animal and human studies are required to identify the true effect of a high steroid dose on outcomes of cardiac arrest survivors.

Our current study has several limitations. First, our analysis of the relationship between patient outcomes and the steroid dose administered is limited by the fact that the NHIRD provided the data of the total dose of steroid in a period of hospitalization rather than data on individual doses and their timing. Also, the reason why postarrest steroid was administered was not provided. We attempted to reduce confounding factors by excluding patients who received steroid greater than 1 month and patients receiving pulse steroid therapy. We also standardized the dose equivalent with the duration of hospitalization. Second, we did not adjust therapeutic hypothermia in our outcome analysis, because hypothermia was not covered by the Taiwan NHI system until 2015, and only a few such cases were reported. Besides, the general quality-improvement measures may narrow the difference between groups. Therefore, we attempted to attenuate the potential variance of postcardiac arrest care by matching the steroid and nonsteroid groups for hospital level and the geographic distribution of hospitals. In addition, we also matched epinephrine and shockable rhythm, two important survival-related variables, to reduce the potential confounders. Third, individual patient information, including body weight, smoking history, witnessed collapse, bystander CPR, cause of cardiac arrest, hemodynamics during and after CPR, the reason for steroid use, plasma cortisol and adrenocorticotropic hormone concentrations, causes of death, and neurologic outcomes were not available in the Taiwan NHIRD. Fourth, the effect of unmeasured confounders cannot be controlled using PS matching, such that causality cannot be inferred. Finally, the doses and routes of steroids prior to cardiac arrest were not investigated and worth exploring in the further appropriately designed studies.