Contentious Use of Corticosteroids in The Critically Ill

 

There is a long-drawn-out history with the use of corticosteroids in septic shock. In the 1980s, methylprednisolone was used in industrial strengths as a short course treatment, with predictably poor results.[1]After several studies that suggested poor outcomes in septic shock, the use of corticosteroids slowly faded away. However, in the 1990s, there was a rekindling of interest with the use of corticosteroids in lower, more physiological doses, as replacement therapy, considering the possibility of “relative adrenal insufficiency” in septic shock. Three adequately powered randomized controlled trials have been published with the use of “physiological” dose corticosteroids in septic shock (Annane et al.[2], Corticus[3], and ADRENAL[4]). A pooled analysis of these three studies does not demonstrate improved survival with the use of corticosteroids in septic shock.

 

Fig 1. A pooled analysis of studies on mortality with the use of corticosteroids in septic shock 

However, earlier shock reversal seems likely with the use of corticosteroids, as evidenced in most of the studies. The ADRENAL trial also revealed marginally lower ventilation days with corticosteroid use (6 vs. 7 days) with the initial episode of mechanical ventilation; however, there was no difference between groups with days alive and free of ventilation.

Severe acute respiratory distress syndrome (ARDS) may follow several acute illnesses, including sepsis, trauma, and acute pancreatitis. Corticosteroids are often used in patients who continue to remain hypoxic after optimization of mechanical ventilation. Meduri et al. carried out two RCTs,[5],[6]with 1:2 randomization. Both studies seemed to favor the use of corticosteroids, with improved lung injury scores, improved oxygenation, and less time on ventilation. However, the results of the ARDSnet study of 180 patients with ARDS was different.[7] Although steroid use was associated with improved P/F ratios and other parameters of respiratory physiology, there was no difference in the 60 or 180-day mortality. A pooled analysis of these three trials and a recent RCT does not show any survival advantage with the use of corticosteroids in ARDS

fig 2.jpg

Fig 2. A pooled analysis of studies on mortality with the use of corticosteroids in ARDS

Are corticosteroids beneficial in community-acquired pneumonia (CAP)? One of the early studies on critically ill patients revealed improved P/F ratios, earlier resolution of shock, shorter hospital stay, and improved mortality.[8]Subsequently, there have been several small RCTs that evaluated the possible beneficial effect of corticosteroids in CAP[9],[10],[11],[12],[13],[14]. Most of these studies have been performed on patients with a low severity of illness, and low mortality. A pooled analysis of all studies carried out after 2005 suggests a mortality benefit with the use of corticosteroids (Fig 3). 

fig 3

Fig 3. A pooled analysis of studies on mortality with the use of corticosteroids in community-acquired pneumonia 

However, several questions remain unanswered. Viral pneumonias are notorious to lead to a severe disease with profound impairment of oxygenation on occasions. We are seeing a resurgence of severe H1N1 pneumonia after several years in India. Would corticosteroids be of benefit in these patients? There are no robust data available to guide us in this situation. The limited evidence available so far seems to suggest that corticosteroids may have either have no effect or even be harmful in viral pneumonias.

References

[1] Veterans Administration Systemic Sepsis Cooperative Study Group, Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis.  N Engl J Med (1987);317659- 665

[2] Annane D1Sébille VCharpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.JAMA. 2002 Aug 21;288(7):862-71.

[3] Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. New England Journal of Medicine. 2008 Jan 10;358(2):111.

[4] Venkatesh B, Finfer S, Cohen J, Rajbhandari D, Arabi Y, Bellomo R, Billot L, Correa M, Glass P, Harward M, Joyce C. Adjunctive glucocorticoid therapy in patients with septic shock. New England Journal of Medicine. 2018 Mar 1;378(9):797-808.

[5] Meduri GU, Headley AS, Golden E, Carson SJ, Umberger RA, Kelso T, Tolley EA. Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. Jama. 1998 Jul 8;280(2):159-65.

[6] Meduri GU, Golden E, Freire AX, et al. Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest. 2007 Apr 1;131(4):954-63.

[7] National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. New England Journal of Medicine. 2006 Apr 20;354(16):1671-84.

[8] Confalonieri M, Urbino R, Potena A, et al.  Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit Care Med. 2005 Feb 1;171(3):242-8.

[9] Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. The Lancet. 2015 Apr 18;385(9977):1511-8.

[10] Fernández-Serrano S, Dorca J, Garcia-Vidal C, et al. Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial. Critical Care. 2011 Apr;15(2):R96.

[11] Meijvis SC, Hardeman H, Remmelts HH, et al. Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial. The Lancet. 2011 Jun 11;377(9782):2023-30.

[12] Sabry NA, Omar EE. Corticosteroids and ICU course of community acquired pneumonia in Egyptian settings. Pharmacology & Pharmacy. 2011 Apr 25;2(02):73.

[13] Snijders D, Daniels JM, de Graaff CS, et al. Efficacy of corticosteroids in community-acquired pneumonia: a randomized double-blinded clinical trial. American journal of respiratory and critical care medicine. 2010 May 1;181(9):975-82.

[14] Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. Jama. 2015 Feb 17;313(7):677-86.

 

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