Hydrocortisone Versus Hydrocortisone Plus Fludrocortisone for the Treatment of Adrenal Insufficiency in Severe Sepsis

Inclusion Criteria: Males and non-pregnant females > 18 years of age Patients admitted and/or pending admission to the intensive care unit Positive corticotropin stimulation test (Basal cortisol level of ≤ 34 μg/dL with Δ ≤ 9 μg/dL after administration of 250 mg of cosyntropin) Patient satisfies criteria for severe sepsis Infection - one or more of the following criteria Documented or Suspected - positive culture results (from blood, sputum, urine, etc.) Anti-Infective Therapy - patient is receiving antibiotic, antifungal, or other anti-infective therapy Pneumonia - documentation of pneumonia (x-ray, etc.) WBCs - WBCs found in normally sterile .uid (urine, CSF, etc.) Perforated Viscus - perforation of hollow organ (bowel) SIRS - two or more of the following Temperature > 38° or < 36° Heart rate > 90 bpm Respiratory rate above 20 breaths per minute WBC > 14,000/mm3 , < 4000/mm3, or >10% Bands Acute organ dysfunction - one or more of the following Cardiovascular - SBP < 90 mmHg or MAP < 70 mmHg despite 20 mL/kg of fluid resuscitation Respiratory - PaO2/FiO2 ratio < 250, PEEP > 7.5, or require mechanical ventilation Renal - low urine output (eg, <0.5 mL/kg/hr for 1 hour despite 20mL/kg of fluid resuscitation, increased creatinine (>50% increase from baseline) or require acute dialysis Hematologic - low platelet count (< 100,000/mm3) or PT/PTT > upper limit of normal Metabolic - low pH with high lactate (eg, pH < 7.30 and plasma lactate > upper limit of normal Hepatic - liver enzymes > 2x upper limit of normal CNS - altered consciousness or reduced Glasgow Coma Score Exclusion Criteria: Patients who respond to the short cosyntropin stimulation test(Δ > 9mg/dL) Pregnancy or breast-feeding mother Evidence of acute myocardial infarction, meningitis, pulmonary embolism AIDS (CD4 < 200 cells/mL) Contraindications for corticosteroids Formal indication for corticosteroids (specifically including patients with known adrenal insufficiency) Onset of shock > 24 hours Etomidate administration within the 6 hours preceding randomization Cardiac arrest prior to randomization.