Microcirculatory perfusion disturbances following cardiopulmonary bypass: a systematic review

Abstract

Background: Microcirculatory perfusion disturbances are associated with increased morbidity and mortality in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Technological advancements made it possible to monitor sublingual microcirculatory perfusion over time. The goal of this review is to provide an overview of the course of alterations in sublingual microcirculatory perfusion following CPB. The secondary goal is to identify which parameter of sublingual microcirculatory perfusion is most profoundly affected by CPB.

Methods: PubMed and Embase databases were systematically searched according to PRISMA guidelines and as registered in PROSPERO. Studies that reported sublingual microcirculatory perfusion measurements before and after onset of CPB in adult patients undergoing cardiac surgery were included. The primary outcome was sublingual microcirculatory perfusion, represented by functional capillary density (FCD), perfused vessel density (PVD), total vessel density (TVD), proportion of perfused vessels (PPV), and microvascular flow index (MFI).

Results: The search identified 277 studies, of which 19 fulfilled all eligibility criteria. Initiation of CPB had a profound effect on FCD, PVD, or PPV. Seventeen studies (89%) reported one or more of these parameters, and in 11 of those studies (65%), there was a significant decrease in these parameters during cardiac surgery; the other 6 studies (35%) reported no effect. In 29% of the studies, FCD, PVD, or PPV normalized by the end of cardiac surgery, and in 24% percent of the studies, this effect lasted at least 24 h. There was no clear effect of CPB on TVD and a mixed effect on MFI.

Conclusion: CPB during cardiac surgery impaired sublingual microcirculatory perfusion as reflected by reduced FCD, PVD, and PPV. Four studies reported this effect at least 24 h after surgery. Further research is warranted to conclude on the duration of CPB-induced microcirculatory perfusion disturbances and the relationship with clinical outcome.

Trial registration: PROSPERO, CRD42019127798.

Keywords: Capillary perfusion; Cardiac surgery; Cardiopulmonary bypass; Microcirculation; Microcirculatory perfusion; Sublingual.

Fig. 1

PRISMA flow diagram representing the flowchart of study selection. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Fig. 2

Summary figure. Cardiac surgery with cardiopulmonary bypass impairs microcirculatory perfusion, which is monitored sublingually in patients in the perioperative period. Onset of cardiopulmonary bypass reduces sublingual microcirculatory perfusion reflected by functional capillary density (FCD), proportion of perfused vessels (PPV), and perfused vessel density (PVD) compared to baseline, whereas total vessel density (TVD) remained unaltered. The effect of cardiopulmonary bypass on microvascular flow index (MFI) differed between studies. Pathophysiological mechanisms include systemic inflammation, and activation of complement and coagulation, which causes shedding of the endothelial protective glycocalyx layer leading to endothelial injury. In addition, release of barrier disruptive mediators induce endothelial barrier disruptive signaling, resulting in capillary leakage and edema formation. Activation of the endothelium stimulates the release of nitric oxide (NO), affecting vascular tone and systemic blood pressure. Moreover, induction of endothelial adhesion molecule expression increases leucocyte rolling and extravasation. Also, activation of polymorphonuclear neutrophils causes the release of reactive oxygen species (ROS), contributing to tissue injury. Activation of platelets and coagulation are associated with the formation of microthrombi and microvascular occlusion. Collectively, these mechanisms impair microcirculatory perfusion and contribute to organ injury following cardiac surgery with cardiopulmonary bypass, with clinical and experimental treatment strategies presented in italic in white boxes. IL, interleukin; IFNy, interferon gamma; TNFα, tumor necrosis factor alpha