Stress Doses of Hydrocortisone Reduce Severe Systemic Inflammatory Response Syndrome and Improve Early Outcome in a Risk

Objective: Severe systemic inflammation with a vasodilatory syndrome occurs in about one third of all patients after cardiac surgery with cardiopulmonary bypass. Hydrocortisone has been used successfully to reverse vasodilation in septic patients. We evaluated if stress doses of hydrocortisone attenuate severe systemic inflammatory response syndrome in a predefined risk group of patients after cardiac surgery with cardiopulmonary bypass.


Design: Randomized, nonblinded, controlled trial.
Setting: Anesthesiologic intensive care unit for cardiac surgical patients of an university hospital.
Patients: After a risk analysis, we enrolled 91 patients into a prospective randomized trial. Patients were included according to the evaluated criteria (preoperative ejection fraction, duration of cardiopulmonary bypass, type of surgery).


Interventions: The treatment group received stress doses of hydrocortisone perioperatively: 100 mg before induction of anesthesia, then 10 mg/hr for 24 hrs, 5 mg/hr for 24 hrs, 3 20 mg/day, and 3 10 mg/day.


Measurements and Main Results: We measured various laboratory (e.g., lactate) and clinical variables (e.g., duration of ventilation and length of stay in the intensive care unit), characterizing the patients’ outcome. The two study groups did not differ regarding age, preoperative medication, duration of the cardiopulmonary bypass, and type of surgery. The patients in the treatment group had significantly lower concentrations of IL-6 and lactate, higher antithrombin III concentration, lower need for circulatory and ventilatory support and for transfusions, lower Therapeutic Intervention Scoring System values, and shorter length of stay in the intensive care unit and in the hospital. The mortality rate did not differ significantly between the groups.


Conclusions: Although we acknowledge the limitations of a nonblinded interventional trial, stress doses of hydrocortisone seem to attenuate systemic inflammation in a predefined risk group of patients after cardiac surgery with cardiopulmonary bypass and improve early outcome.

Introduction
Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) may develop systemic inflammatory response syndrome (SIRS) in the postoperative period, which increases perioperative morbidity and might increase mortality rate. SIRS is considered to be the result of a complex immunologic reaction consisting of humoral, cellular, and hemostatic factors,Ä1Å caused by an imbalance of pro- and anti-inflammatory mechanisms.Ä2Å The majority of patients recover without any lasting sequelae from cardiac surgery. However, a subgroup of patients develop severe systemic inflammation, associated with significant hypotension due to vasodilation, called vasodilatory syndrome (VDS).Ä3Å Several risk factors have been proposed to be associated with severe SIRS with VDS after CPB (i.e., duration of CPB, poor preoperative left ventricular performance, and preoperative medication with angiotensin-converting enzyme inhibitors). The incidence of complicationsÄ4Å is very high, ranging from prolonged catecholamine dependency to multiple-organ failure. Various technical (e.g., heparin-bonded circuitry, membrane oxygenator, leukocyte depletion) and pharmacologic (e.g., aprotinin) strategies have been suggestedÄ5-7Å to counterbalance the organism’s inflammatory reaction. Corticosteroids have been studied extensively in recent years, but no study could reveal a definitive clinical benefit regarding patients’ outcome.Ä8Å

To our knowledge, no study has yet been published that investigated the effect of an anti-inflammatory prophylaxis in a predefined high-risk group of patients.


Hydrocortisone has been shown to accelerate reversal from septic shock and may even reduce mortality rate from septic shock.Ä9Å Based on the assumption that the pathophysiologies of sepsis and severe SIRS caused by CPB share several immunologic mechanisms, patients with severe inflammation also should benefit especially from prophylactic treatment. Thus, we performed a prospective, randomized interventional trial to test the hypothesis that stress doses of hydrocortisoneÄ10Å attenuate severe inflammatory response in a predefined risk group of patients after cardiac surgery with CPB.