Executive Summary: Guidelines on Use of Corticosteroids in Critically Ill Patients With Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia Focused Update 2024

Critical illness-related corticosteroid insufficiency (CIRCI) is a state of systemic inflammation with associated dysregulation of the hypothalamus–pituitary–adrenal axis, altered cortisol metabolism, and tissue glucocorticoid resistance (1) that is common in acutely ill patients requiring hospitalization. A multispecialty task force of international experts in critical care medicine and endocrinology from the membership of the Society of Critical Care Medicine and European Society of Intensive Care Medicine previously issued guidelines on the diagnosis of and management of CIRCI across a number of clinical conditions, first in 2008 (2) and then in 2017 (3,4). Since then, multiple new trials examining the use of corticosteroids in the acutely ill have been published, creating a need to update recommendations inclusive of new evidence. This executive summary provides an update on the previous guidelines on CIRCI, with a focus on sepsis and septic shock, acute respiratory distress syndrome (ARDS), and community-acquired pneumonia (CAP), which were prioritized as the most common diagnoses in which corticosteroids are considered and those with sufficient new data that reevaluation was warranted. After development of five focused Population, Intervention, Control, and Outcomes questions for this focused update, the panel conducted systematic reviews to identify the best available evidence addressing each question. We evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach and formulated recommendation using the evidence-to-decision framework. The strength of each recommendation was designated as strong (signified by “we recommend”) or conditional (signified by “we suggest”). The panel sought to provide recommendations in both adult and pediatric patient populations, as appropriate, based on available evidence. A summary of recommendations is provided in Table 1. A full description of the recommendations is provided in the complete guidelines document. TABLE 1. - Summary of Recommendations Recommendations Recommendation Strength, Quality of Evidence Septic shock 1A. We “suggest” administering corticosteroids to adult patients with septic shock Conditional recommendation, low certainty evidence 1B. We “recommend against” administration of high dose/short duration corticosteroids (> 400 mg/d hydrocortisone equivalent for less than 3 d) for adult patients with septic shock (strong recommendation, low certainty) Strong recommendation, moderate certainty evidence Acute respiratory distress syndrome 2A. We “suggest” administering corticosteroids to adult hospitalized patients with acute respiratory distress syndrome Conditional recommendation, moderate certainty evidence Community-acquired bacterial pneumonia 3A. We “recommend” administering corticosteroids to adult patients hospitalized with severe bacterial community acquired pneumonia Strong recommendation, moderate certainty evidence Corticosteroids in Sepsis and Septic Shock Recommendation 1A) We suggest administering corticosteroids to adult patients with septic shock (conditional recommendation, low certainty). 1B) We recommend against administration of high dose/short duration corticosteroids (defined as > 400 mg/d of hydrocortisone equivalent for < 3 d) for adult patients with septic shock (strong recommendation, moderate certainty). Remark: We make no recommendation for corticosteroid use in pediatric patients with sepsis. Rationale Most studies included patients with septic shock and showed small to moderate desirable effects. Although there was only a small reduction in mortality with low to moderate certainty evidence, there was a larger reduction in shock reversal and organ dysfunction with high certainty evidence (3,5–10). The panel felt that given the high prevalence of septic shock worldwide, even a small reduction in mortality can have a large effect and that the reduction in shock reversal and organ dysfunction can have important implications in resource utilization. Undesirable effects were felt to be uncertain but anticipated to be small. Further, the intervention was deemed feasible, equitable and acceptable to healthcare providers. The panel did not make a specific recommendation regarding corticosteroid regimen, but recommended against use of high dose, short duration corticosteroids given the risk of adverse effects. Although the panel did not make a specific recommendation on sepsis without shock, if patients present with sepsis and severe CAP or sepsis with ARDS, we suggest administering corticosteroids. Finally, the recommendation for corticosteroid use in sepsis has uncertain generalizability to the pediatric population due to limited available studies. Corticosteroids in Acute Respiratory Distress Syndrome Recommendations 2A) We “suggest” administering corticosteroids to adult critically ill patients with ARDS (conditional recommendation, moderate certainty). Remark: We make no recommendation for corticosteroid use in pediatric patients with ARDS. Rationale Corticosteroids provide moderate desirable effects, driven primarily by moderate certainty evidence that it reduces hospital mortality (3,11–15). This effect is more pronounced when corticosteroids are given for more than 7 days. However, the ideal corticosteroid dose, timing, and type remains unknown and left up to clinician comfort and other considerations. This is in contrast to the previous recommendation in 2017 that suggested giving methylprednisolone 1 mg/kg within 14 days of diagnosis of ARDS (3). Undesirable effects of corticosteroids and their cost-effectiveness remain unknown. However, corticosteroid use was deemed feasible and acceptable to healthcare providers. Overall, the panel felt that the benefits of corticosteroid use outweighed its risks. The recommendation has uncertain generalizability to pediatric patients as there were no randomized controlled trials in this population. Corticosteroids in Community-Acquired Pneumonia Recommendations 3A) We “recommend” administering corticosteroids for adult patients hospitalized with severe bacterial community-acquired pneumonia (strong recommendation, moderate certainty). Remark: We make no recommendation for corticosteroid use in pediatric patients with CAP. Rationale Corticosteroids provide large desirable effects in severe CAP with moderate certainty evidence indicating a decrease in hospital mortality and need for invasive mechanical ventilation (4,16,17). The same mortality benefit is not seen in patients with less severe CAP (4,18,19). Undesirable effects, while unknown as with ARDS and sepsis, are anticipated to be small. Use of corticosteroids in CAP was felt to be feasible, acceptable and may be associated with cost savings (20). As with sepsis and ARDS, the panel was unable to make recommendations on use of corticosteroids for CAP in pediatric patients due to lack of available literature.

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