Review Article

Attenuating the Systemic Inflammatory Response to Adult Cardiopulmonary Bypass: A Critical Review of the Evidence Base

^* Edmund Cohen Laboratory for Vascular Research, The University of the West Indies, Bridgetown, Barbados
^† The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
^‡ INOVA Heart and Vascular Institute, Indiana OVA Fairfax Hospital for Children, Falls Church, Virginia
^§ Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan
^‖ Department of Anesthesiology, Hofstra Northshore-LIJ Medical School, New Hyde Park, New York
^¶ Cardiac Surgery Research and Perfusion, Flinders University and Flinders Medical Centre, Adelaide, South Australia
^** Department of Cardiothoracic Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Address correspondence to: R. Clive Landis, PhD, Edmund Cohen Laboratory for Vascular Research, Chronic Disease Research Centre, University of the West Indies, Barbados BB11115. E-mail: clive.landis@cavehill.uwi.edu

Received: 19 August 2014
Accepted: 20 August 2014

Abstract

A wide range of pharmacological, surgical, and mechanical pump approaches have been studied to attenuate the systemic inflammatory response to cardiopulmonary bypass, yet no systematically based review exists to cover the scope of anti-inflammatory interventions deployed. We therefore conducted an evidence-based review to capture “self-identified” anti-inflammatory interventions among adult cardiopulmonary bypass procedures. To be included, trials had to measure at least one inflammatory mediator and one clinical outcome, specified in the “Outcomes 2010” consensus statement. Ninety-eight papers satisfied inclusion criteria and formed the basis of the review. The review identified 33 different interventions and approaches to attenuate the systemic inflammatory response. However, only a minority of papers (35 of 98 [35.7%]) demonstrated any clinical improvement to one or more of the predefined outcome measures (most frequently myocardial protection or length of intensive care unit stay). No single intervention was supported by strong level A evidence (multiple randomized controlled trials [RCTs] or meta-analysis) for clinical benefit. Interventions at level A evidence included off-pump surgery, minimized circuits, biocompatible circuit coatings, leukocyte filtration, complement C5 inhibition, preoperative aspirin, and corticosteroid prophylaxis. Interventions at level B evidence (single RCT) for minimizing inflammation included nitric oxide donors, C1 esterase inhibition, neutrophil elastase inhibition, propofol, propionyl-L-carnitine, and intensive insulin therapy. A secondary analysis revealed that suppression of at least one inflammatory marker was necessary but not sufficient to confer clinical benefit. The most effective interventions were those that targeted multiple inflammatory pathways. These observations are consistent with a “multiple hit” hypothesis, whereby clinically effective suppression of the systemic inflammatory response requires hitting multiple inflammatory targets simultaneously. Further research is warranted to evaluate if combinations of interventions that target multiple inflammatory pathways are capable of synergistically reducing inflammation and improving outcomes after cardiopulmonary bypass.