Guidelines for the Diagnosis and Management of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) in Critically Ill Patients (Part I)

Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017

Djillali Annane, MD, PhD; Stephen M. Pastores, MD, FCCM; Bram Rochwerg, MD; Wiebke Arlt, MD, DSc, FRCP; Robert A. Balk, MD, MCCM; Albertus Beishuizen, MD, PhD; Josef Briegel, MD, PhD; Joseph Carcillo, MD, FCCM; Mirjam Christ-Crain, MD, PhD; Mark S. Cooper, MD; Paul E. Marik, MD, FCCM; Gianfranco Umberto Meduri, MD; Keith M. Olsen, PharmD, FCCM; Sophia C. Rodgers, RN, MSN, ACNP, FCCM; James A. Russell, MD; Greet Van den Berghe, MD, PhD


Crit Care Med. 2017;45(12):2078-2088. 

In This Article

Abstract and Introduction


Objective: To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients.

Participants: A multispecialty task force of 16 international experts in critical care medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine.

Design/Methods: The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members.

Results: The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of < 9 μg/dL) after cosyntropin (250 μg) administration and a random plasma cortisol of < 10 μg/dL may be used by clinicians. We suggest against using plasma-free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using IV hydrocortisone < 400 mg/day for ≥ 3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO2/FiO2 < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence).

Conclusions: Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.


Critical illness-related corticosteroid insufficiency (CIRCI) is a concept that was first introduced in 2008 by an international multidisciplinary task force convened by the Society of Critical Care Medicine (SCCM) to describe impairment of the hypothalamic pituitary axis (stress response) during critical illness.[1] CIRCI is characterized by dysregulated systemic inflammation resulting from inadequate intracellular glucocorticoid-mediated anti-inflammatory activity for the severity of the patient's critical illness. The putative symptoms of CIRCI are listed in Table 1. CIRCI is associated with increased circulating levels of biological markers of inflammation and coagulation over time, morbidity, length of ICU stay, and mortality. Given the growing body of evidence that CIRCI occurs across a broad spectrum of critical illness, an understanding of the pathogenesis and treatment of CIRCI is important to all critical care providers.

Two emerging themes made it necessary to revisit the concept, diagnosis, and management of CIRCI:[1] the recognition of the importance of evidence-based approaches to patient care to enhance quality, improve safety, and establish a clear and transparent framework for service development and healthcare provision;[2] the widespread use of corticosteroids in critically ill patients, highlighting the need for a valid, reliable, and transparent process of evaluation to support key decisions.

Against this background, the SCCM and the European Society of Intensive Care Medicine (ESICM) have updated the 2008 guidelines for the diagnosis and treatment of CIRCI. In addition to rigorous application of GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology, the recommendations in this document focus on patient-important outcomes and utility to clinicians in everyday practice. It was not intended to define a standard of care, and should not be interpreted as such. As with any clinical practice guideline, it should not be interpreted as prescribing an exclusive course of management. The guideline covers CIRCI in critically ill children and adults. It does not cover chronic adrenal insufficiency and does not apply to neonates, because the guideline panel felt these areas represented separate fields of expertise. This guideline focuses on the three disorders that most clinicians associate with CIRCI: sepsis/septic shock, acute respiratory distress syndrome, and major trauma.