Society of Cardiovascular Anesthesiologists

Literature Reviews

Combined steroid treatment for congenital heart surgery improves oxygen delivery and reduces postbypass inflammatory mediator expression.

Schroeder VA, Pearl JM, Schwartz SM, Shanley TP, Manning PB, Nelson DP. Circulation 107:2823-2828, 2003.

Reviewer: Mark A. Chaney, MD
University of Chicago

Abstract Excerpt: Steroid administration during cardiopulmonary bypass is thought to improve cardiopulmonary function by modulating bypass-related inflammation. This investigation compared preoperative and intraoperative methylprednisolone (MP) to intraoperative MP alone with respect to postbypass inflammation and clinical outcome. Twenty-nine pediatric patients undergoing bypass procedures were randomly assigned to receive preoperative and intraoperative MP (30 mg/kg four hours before bypass and in bypass prime, n=14) or intraoperative MP only (30 mg/kg, n=15). Myocardial inflammatory mediator mRNA expression was determined in paired atrial biopsies (before and after bypass) by ribonuclease protection. Before and after bypass, serum IL-6 and IL-10 were measured by ELISA. Postoperative outcome was assessed by intubation time, CICU length of stay, fluid balance, arterio-venous oxygen difference, and inotrope requirements. Compared with intraoperative MP alone, combined preoperative and intraoperative MP was associated with reduced myocardial mRNA expression for IL-6, MCP-1, and ICAM-1 both before and after bypass (p < 0.05). Patients who received combined steroids had lower serum IL-6 and increased IL-10 at end-bypass (p < 0.05), although differences were negligible by twenty-four hours. Combined MP treatment was associated with reduced fluid requirements, lower body temperature, and lower arterio-venous oxygen difference for the first twenty-four hours after surgery (p < 0.05), along with trends toward improvement in other clinical outcomes. The investigators conclude that, compared with intraoperative steroid treatment, combined preoperative and intraoperative steroid administration attenuates inflammatory mediator expression more effectively and is associated with improved indexes of oxygen delivery in the first twenty-four hours after congenital heart surgery.

Reviewer's Comments: Cardiopulmonary bypass exposes blood to large areas of synthetic materials that trigger the production and release of numerous chemotactic and vasoactive substances. This ensuing abnormal whole-body inflammatory response can complicate the postoperative period by causing major organ dysfunction. Traditionally, corticosteroids have been administered to patients undergoing cardiac surgery to ward off these detrimental physiologic alterations. In the late 1960s, MP became the steroid of choice because of its antiinflammatory potency and minimal tendency to induce sodium and water retention. However, few well-controlled investigations exist, and use of the drug in this setting remains controversial. Previous clinical investigations suggest that MP reliably alters favorably the balance of proinflammatory and antiinflammatory mediators in the blood of patients subjected to cardiopulmonary bypass, indicating that the drug decreases the systemic inflammatory response associated with bypass. Specific hemodynamic benefits such as increased cardiac index and decreased systemic vascular resistance wasto be associated with use of the drug in this setting, yet these alterations may increase the need for postoperative vasoconstrictors. From a pulmonary perspective, the use of MP in this setting does not appear to offer any clinical benefits and may be detrimental. The drug was unable to reliably prevent postoperative decreases in pulmonary compliance and increases in alveolar-arterial oxygen difference and may hinder early postoperative tracheal extubation for undetermined reasons. Lastly, while MP was unable to beneficially affect perioperative fluid balance , it was clear that the drug increased perioperative blood glucose levels.

Although steroids have been used for many years to attenuate postbypass inflammation, data to support this application stem almost entirely from trials in adults with coronary artery disease and clinical studies have chiefly compared placebo with steroid administration during or immediately preceding bypass. Recent data from animal models suggest that combined preoperative and intraoperative steroid administration may provide superior anti-inflammatory benefits. The rationale for combined preoperative and intraoperative steroid therapy is that this may inhibit activation of bypass-mediated inflammatory cascades more effectively than intraoperative treatment alone. To test whether combined preoperative and intraoperative MP is superior to intraoperative MP alone, this small, prospective, randomized clinical trial was performed to compare inflammatory mediator induction and clinical outcome. The investigators found that pediatric patients treated with combined preoperative and intraoperative MP had lower myocardial and systemic inflammatory mediator expression, which corresponded to enhanced indices of oxygen delivery, lower body temperature, reduced fluid requirements, and a trend toward shorter intensive care unit length of stay. Novel observations from this investigation include that combined steroid treatment reduced inflammatory mediator expression in the heart directly and that steroid pretreatment reduced myocardial inflammatory mediator expression before bypass, thus indicating that antiinflammatory effects of preoperative steroid treatment preceded both myocardial ischemia and activation of blood elements by the extracorporeal circuit. In sum, the data support the hypothesis that combined preoperative and intraoperative steroid administration reduces bypass-related inflammation more effectively than intraoperative treatment alone.

Additional well-designed clinical investigations with large numbers of patients involving corticosteroids and patients undergoing cardiac surgery with cardiopulmonary bypass need to be done. Whether or not suppression of the systemic inflammatory response associated with cardiopulmonary bypass with corticosteroids is clinically desirable and beneficial remains to be determined. This small clinical investigation adds additional data to support the contention that corticosteroids are beneficial to patients undergoing cardiac surgery associated with cardiopulmonary bypass. However, this debate remains unsettled, and will likely remain so for quite some time.

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