Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine.
OBJECTIVE
To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients.


METHODS
A multidisciplinary, multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. In addition, international experts in endocrinology were invited to participate.


METHODS
The task force members reviewed published literature and provided expert opinion from which the consensus was derived. The consensus statements were developed using a modified Delphi methodology. The strength of each recommendation was quantified using the Modified GRADE system, which classifies recommendations as strong (grade 1) or weak (grade 2) and the quality of evidence as high (grade A), moderate (grade B), or low (grade C) based on factors that include the study design, the consistency of the results, and the directness of the evidence.


RESULTS
The task force coined the term critical illness-related corticosteroid insufficiency to describe the dysfunction of the hypothalamic-pituitary-adrenal axis that occurs during critical illness. Critical illness-related corticosteroid insufficiency is caused by adrenal insufficiency together with tissue corticosteroid resistance and is characterized by an exaggerated and protracted proinflammatory response. Critical illness-related corticosteroid insufficiency should be suspected in hypotensive patients who have responded poorly to fluids and vasopressor agents, particularly in the setting of sepsis. At this time, the diagnosis of tissue corticosteroid resistance remains problematic. Adrenal insufficiency in critically ill patients is best made by a delta total serum cortisol of < 9 microg/dL after adrenocorticotrophic hormone (250 microg) administration or a random total cortisol of < 10 microg/dL. The benefit of treatment with glucocorticoids at this time seems to be limited to patients with vasopressor-dependent septic shock and patients with early severe acute respiratory distress syndrome (PaO2/FiO2 of < 200 and within 14 days of onset). The adrenocorticotrophic hormone stimulation test should not be used to identify those patients with septic shock or acute respiratory distress syndrome who should receive glucocorticoids. Hydrocortisone in a dose of 200 mg/day in four divided doses or as a continuous infusion in a dose of 240 mg/day (10 mg/hr) for > or = 7 days is recommended for septic shock. Methylprednisolone in a dose of 1 mg x kg(-1) x day(-1) for > or = 14 days is recommended in patients with severe early acute respiratory distress syndrome. Glucocorticoids should be weaned and not stopped abruptly. Reinstitution of treatment should be considered with recurrence of signs of sepsis, hypotension, or worsening oxygenation. Dexamethasone is not recommended to treat critical illness-related corticosteroid insufficiency. The role of glucocorticoids in the management of patients with community-acquired pneumonia, liver failure, pancreatitis, those undergoing cardiac surgery, and other groups of critically ill patients requires further investigation.


CONCLUSIONS
Evidence-linked consensus statements with regard to the diagnosis and management of corticosteroid deficiency in critically ill patients have been developed by a multidisciplinary, multispecialty task force.
Marik
Paul E
PE
Division of Pulmonary and Critical Care Medicine, Thomas Jefferson University, Philadelphia, PA, USA. paul.marik@jefferson.edu
Pastores
Stephen M
SM
Annane
Djillali
D
Meduri
G Umberto
GU
Sprung
Charles L
CL
Arlt
Wiebke
W
Keh
Didier
D
Briegel
Josef
J
Beishuizen
Albertus
A
Dimopoulou
Ioanna
I
Tsagarakis
Stylianos
S
Singer
Mervyn
M
Chrousos
George P
GP
Zaloga
Gary
G
Bokhari
Faran
F
Vogeser
Michael
M
D000305:Adrenal Cortex Hormones / Q000172:deficiency*; D000309:Adrenal Insufficiency / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D000324:Adrenocorticotropic Hormone; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D003422:Critical Care; D003697:Delphi Technique; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019317:Evidence-Based Medicine; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007262:Infusions, Intravenous; D008775:Methylprednisolone / Q000008:administration & dosage; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D008775:Methylprednisolone