Pharmacological interventions to reduce edema following cardiopulmonary bypass: A systematic review and meta-analysis

Abstract

Purpose: To compare the effectiveness of different types of pharmacological agents to reduce organ specific edema following cardiopulmonary bypass (CPB).

Methods: Pubmed, Embase.com and Cochrane were searched for studies administrating a pharmacological agent before CPB. Primary outcome was postoperative edema.

Results: Forty-four studies (clinical n = 6, preclinical n = 38) fulfilled eligibility criteria. Steroids were used in most clinical studies (n = 5, 83%) and reduced postoperative edema in 4 studies, however heterogeneity precluded meta-analysis. In preclinical studies, a total of 31 different drugs were tested of which 20 (65%) reduced edema in at least one organ. Particularly neutrophil inhibitors, and modulators of coagulation or endothelial barrier reduced pulmonary edema (SMD -2.77 [-3.93, -1.61]; -1.29 [-2.12, -0.46], -2.33 [-4.69, 0.03], respectively) compared to no treatment. Reducing renal (SMD -0.91 [CI -1.65 to -0.18]), intestinal (SMD -1.98 [CI -3.92 to -0.04]) or myocardial (SMD -1.95 [CI -3.91 to -0.01]) edema following CPB required specific modulators of endothelial barrier.

Conclusion: Overall, neutrophil inhibitors and direct modulators of endothelial barrier (PAR1, Tie2 signaling) most effectively reduced edema following CPB, in particular pulmonary edema. Future research should focus on a combination of these strategies to reduce edema and assess the effect on organ function and outcome following CPB.

Keywords: Capillary permeability; Cardiac surgery; Cardiopulmonary bypass; Edema; Endothelium; Vascular leakage.