Corticosteroids in Pediatric Septic Shock Are Helpful

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Initially, the prospect of explaining why clinicians should consider administering corticosteroids in pediatric septic shock seems daunting. Why? As those that follow this literature are aware, there is no large randomized controlled trial (RCT) to cite in support. We state this up front as it is important and will (rightfully) be one of the primary justifications cited in the accompanying “con” piece. There is no denying this, and no denying that a large trial is warranted. However, it is equally important to recognize that the absence of a large trial alone cannot be used as proof of lack of benefit, and until such a trial has been completed, pediatric intensivists have a decision to make regarding the administration of a cheap, simple, safe, and widely available intervention. In truth, the “pro” side has the easy task. Recent studies have shown that 90% of clinicians already agree that there are certain septic pediatric patients (e.g., fluid and catecholamine resistant) may benefit from corticosteroid administration (1, 2). The problem is that we do not currently have a reliable mechanism by which to identify such patients. So the question really is, until we can reliably identify specific patients who may benefit from adjunctive corticosteroid administration, what is the harm in administering empiric corticosteroids to all children with severe septic shock? The remainder of this article will provide the basic science and epidemiologic literature justifying the crowd’s decision and why we feel that they should continue to consider corticosteroids pending a large RCT.
The supportive evidence for the potential benefits of corticosteroids in pediatric septic shock include physiologic rationale, animal and adult studies, guideline recommendations, and studies of steroid use in other pediatric critical care conditions. Cortisol is a pleotropic hormone that contributes significantly to hemodynamic stability via several mechanisms. It exerts immediate nongenomic effects by decreasing reuptake of norepinephrine (3), augmenting β-adrenergic receptor sensitivity in the heart, and increasing calcium availability in myocardial and vascular smooth muscle cells (4) leading to increased myocardial contractility and vasoconstriction. Cortisol also exerts delayed effects (several hours) through its genomic actions (5), which include inhibition of prostacyclin production and nitric oxide synthetase leading to increased vascular tone (6), stimulation of intercellular adhesion factor from vascular smooth muscle with a resulting decrease in capillary leak (6), and increase in the number of β-adrenergic receptors in the heart resulting in increased myocardial contractility (5). Lack of sufficient cortisol at the cellular level may contribute to significant hemodynamic instability from decreased myocardial contractility, increased vasodilatation, and/or capillary leak syndrome (7, 8). It therefore follows that administration of corticosteroids may improve hemodynamic stability.
In fact, animal- and adult-based studies have demonstrated that corticosteroid administration in septic shock is associated with a rapid stabilization of blood pressure (9) as well as a reduction in time to cessation of vasopressor support (10). In addition, there have been two large RCTs in critically ill adults (11, 12) in the last 10 years, one of which demonstrated benefit that treatment with steroids reduced the risk of death in patients with septic shock and relative adrenal insufficiency without increasing adverse events (11). The other trial found that hydrocortisone did not improve survival or reversal of shock (12) and that use of steroids was associated with an increased risk of infection. The study demonstrating benefit (11) enrolled patients earlier (8 vs 72 hr), limited corticosteroid exposure (7 vs 11 d), and recruited from a higher risk population (61% vs 31.5% baseline mortality) suggesting that a targeted approach to corticosteroid administration in adult patients with septic shock may be beneficial.

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