Glucocorticoids as an Emerging Pharmacologic Agent for Cardiopulmonary Resuscitation

Abstract

Although cardiac arrest (CA) constitutes a major health problem with dismal prognosis, no specific drug therapy has been shown to improve survival to hospital discharge. CA causes adrenal insufficiency which is associated with poor outcome and increased mortality. Adrenal insufficiency may manifest as an inability to increase cortisol secretion during and after cardiopulmonary resuscitation (CPR). Several studies suggest that glucocorticoids during and after CPR seem to confer benefits with respect to return of spontaneous circulation (ROSC) rates and long term survival. They have beneficial hemodynamic effects that may favor their use during CPR and in the early post-resuscitation period. Moreover, they have anti-inflammatory and anti-apoptotic properties that improve organ function by reducing ischemia/reperfusion (I/R) injury. However, glucocorticoid supplementation has shown conflicting results with regard to survival to hospital discharge and neurological outcome. The purpose of this article is to review the pathophysiology of hypothalamic-pituitary-adrenal (HPA) axis during CPR. Furthermore, this article reviews the effects of glucocorticoids use during CRP and the post-resuscitation phase.

Clinical benefits of corticosteroid administration during adult cardiopulmonary resuscitation: A systemic review and meta-analysis

“…The administration of corticosteroids during cardiac arrest has been proposed for decades; however, there is no strong evidence to support the efficacy of steroids to improve the outcomes of resuscitation[ 7 , 19 ]. Recent studies have described cardiac arrest-related adrenal insufficiency, finding that the condition was associated with increased mortality[ 19 , 20 ]. Ito et al [ 20 ] reported that cortisol levels were moderately low during and after cardiac arrest and CPR, which suggests impairment of adrenal function.…”

Expression of Glucocorticoid Receptors in the Early Period After the Return of Spontaneous Circulation Among Patients Who Experienced Cardiac Arrest : A Retrospective Observational Study

“…In this study, we also found that the total plasma cortisol levels were signi cantly higher in patients who experienced CA but ACTH levels were not. High levels of in ammatory cytokines inhibit ACTH release [19]. During critical illness, the body does not su ciently metabolize cortisol [31].…”

“…However, the use of GC during resuscitation improves the survival rate of patients who experienced CA due to its direct anti-in ammatory, immunosuppressive effects, hemodynamic, and positive inotropic effects. All of this ultimately leads to increased stress capacity of the body [19,20]. GC can activate GRs in cells when the body is under stress, thereby increasing both the effectiveness of resuscitation and the discharge survival rate.…”

“…GCs combine with intracellular glucocorticoid receptors (GRs) to exert anti-in ammatory and immunosuppressive effects, and reduce the production as well as the release of in ammatory cytokines [19,20]. The a nity of GRs to GC in circulating monocytes is decreased in patients with acquired immunode ciency syndrome [21].…”

Intra-Arrest Administration of Cyclosporine and Methylprednisolone Does Not Reduce Postarrest Myocardial Dysfunction

“…CCY blocks the mitochondrial permeability transition pore thereby preventing apoptosis and cell death [10] and improving contractility [11, 12], while MP decreases macrophage and leukocyte activation [13]. Both agents also decrease inflammatory cytokine production [10, 14–19].…”