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

The purpose of this study is to determine if the combination of hydrocortisone plus fludrocortisone is more efficacious than hydrocortisone alone in treating 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, \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.