The strength of the recommendations (1A,1B, 1C, 2A, 2B, 2C) are defined at the end of the "Major Recommendations" field.
Critical Illness-Related Corticosteroid Insufficiency
Recommendation 1: Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis in critical illness is best described by the term critical illness–related corticosteroid insufficiency (CIRCI).
Recommendation 2: The terms absolute or relative adrenal insufficiency are best avoided in the context of critical illness.
Diagnosis of Adrenal Insufficiency
Recommendation 3: At this time, adrenal insufficiency in critical illness is best diagnosed by a delta cortisol (after 250 micrograms cosyntropin) of <9 micrograms/dL or a random total cortisol of <10 micrograms/dL.
Strength of Recommendation: 2B
Recommendation 4: The use of free cortisol measurements cannot be recommended for routine use at this time. Although the free cortisol assay has advantages over the total serum cortisol, this test is not readily available. Furthermore, the normal range of the free cortisol in critically ill patients is currently unclear.
Strength of Recommendation: 2B
Recommendation 5: The adrenocorticotrophic hormone (ACTH) stimulation test should not be used to identify those patients with septic shock or acute respiratory distress syndrome (ARDS) who should receive glucocorticoids (GCs).
Strength of Recommendation: 2B
Who to Treat with Glucocorticoids
Recommendation 6: Hydrocortisone should be considered in the management strategy of patients with septic shock, particularly those patients who have responded poorly to fluid resuscitation and vasopressor agents.
Strength of Recommendations: 2B
Recommendation 7: Moderate-dose GC should be considered in the management strategy of patients with early severe ARDS (partial pressure of arterial oxygen/fraction of inspired oxygen [PaO2/FIO2] of <200) and before day 14 in patients with unresolving ARDS. The role of GC treatment in acute lung injury and less severe ARDS (PaO2/FIO2 of >200) is less clear.
Strength of Recommendations: 2B
How to Treat
Recommendation 8: In patients with septic shock, intravenous hydrocortisone should be given in a dose of 200 mg/day in four divided doses or as a bolus of 100 mg followed by a continuous infusion at 10 mg/hr (240 mg/day). The optimal initial dosing regimen in patients with early severe ARDS is 1 mg/kg/day methylprednisolone as a continuous infusion.
Strength of Recommendation: 1B
Recommendation 9: The optimal duration of GC treatment in patients with septic shock and early ARDS is unclear. However, based on published studies and pathophysiological data, patients with septic shock should be treated for ≥7 days before tapering, assuming that there is no recurrence of signs of sepsis or shock. Patients with early ARDS should be treated for ≥14 days before tapering.
Strength of Recommendation: 2B
Recommendation 10: GC treatment should be tapered slowly and not stopped abruptly.
Strength of Recommendation: 2B
Recommendation 11: Treatment with fludrocortisone (50 micrograms orally once daily) is considered optional.
Strength of Recommendation: 2B
Recommendation 12: Dexamethasone is not recommended for the treatment of septic shock or ARDS.
Strength of Recommendation: 1B
Definitions:
Grade of Recommendation/Description |
Benefits vs. Risk and Burdens |
Methodological Quality of Supporting Evidence |
Implications |
1A: Strong recommendation, high quality evidence |
Benefits clearly outweigh risk and burdens or vice versa |
Randomized controlled trials (RCTs) without important limitations or overwhelming evidence from observational studies |
Strong recommendation can apply to most patients in most circumstances without reservation |
1B: Strong recommendation, moderate quality evidence |
Benefits clearly outweigh risk and burdens or vice versa |
RCTs with important limitations or exceptionally strong evidence from observational studies |
Strong recommendation can apply to most patients in most circumstances without reservation |
1C: Strong recommendation, low quality or very low quality evidence |
Benefits clearly outweigh risk and burdens or vice versa |
Observational studies or case series |
Strong recommendation but may change when higher quality evidence becomes available |
2A: Weak recommendation, high quality evidence |
Benefits closely balanced with risk and burden |
RCTs without important limitations or overwhelming evidence from observational studies |
Weak recommendation, best action may differ depending on circumstances or patients or societal values |
2B: Weak recommendation, moderate quality evidence |
Benefits closely balanced with risk and burden |
RCTs with important limitations or exceptionally strong evidence from observational studies |
Weak recommendation, best action may differ depending on circumstances or patients or societal values |
2C: Weak recommendation, low quality or very low quality evidence |
Uncertainty in the estimates of benefits, risks, and burdens; benefits risk and burden may be closely balanced |
Observational studies or case series |
Very weak recommendations; other alternatives may be equally reasonable |