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

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.

Identification of ferroptosis-associated genes exhibiting altered expression in response to cardiopulmonary bypass during corrective surgery for pediatric tetralogy of fallot

“…26 Therefore, limiting the inflammatory response has been an important myocardioprotective intervention during CPB. 26 Clearly, an improved understanding of the molecular mechanism underlying CPB-associated ferroptosis is key to improving myocardioprotective strategies.…”

“…Indeed, it has previously been demonstrated that CPB induces a systemic inflammatory response 24,25 linked to adverse clinical outcomes ranging from mild adverse effects to severe complications and death. 26 Therefore, limiting the inflammatory response has been an important myocardioprotective intervention during CPB. 26 Clearly, an improved understanding of the molecular mechanism underlying CPB-associated ferroptosis is key to improving myocardioprotective strategies.…”

The gut microbiome and cardiac surgery an unusual symphony

“…52 Previous reviews have concluded that no one single intervention used in isolation shows strong evidence in preventing inflammation. Landis et al 82 have proposed a “multiple hit” hypothesis whereby to achieve clinically effective suppression of the immune system required hitting multiple inflammatory targets. 82…”

“…Landis et al 82 have proposed a “multiple hit” hypothesis whereby to achieve clinically effective suppression of the immune system required hitting multiple inflammatory targets. 82…”

Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study

“…It is well recognized that a dysregulated systemic inflammatory response is associated with organ dysfunction (5, 6), as exemplified by the relationship between cytokine levels and the occurrence and severity of acute kidney injury (AKI) (7–9). To date, no pharmacologic interventions are licensed to limit systemic inflammation or protect renal function (10–13).…”