Original article
Cardiovascular
Effects of Methylprednisolone and a Biocompatible Copolymer Circuit on Blood Activation During Cardiopulmonary Bypass

https://doi.org/10.1016/j.athoracsur.2004.07.044Get rights and content

Background

Cardiopulmonary bypass (CPB) induces derangements in physiology characterized by activation of blood pathways that may contribute to multiorgan dysfunction. This trial addresses the efficacy of a biocompatible surface alone and in combination with steroids in inhibiting these changes.

Methods

In a factorial design, patients undergoing coronary artery bypass grafting were randomized (four groups; n = 17 per group) to CPB utilizing control circuits or a circuit prepared with a surface modifying active copolymer (SMA-CPB), with or without methylprednisolone (MPSS, 1 g intravenous). Leukocyte and complement activation, cytokine release, and bradykinin generation were measured. Clinical outcomes (blood loss, transfusion, arterial pressure response, and postoperative cardiac and pulmonary functions) were also examined.

Results

The SMA-CPB was associated with a significant inhibition of elastase release (p = 0.026) and bradykinin generation (p = 0.027) during CPB. Terminal complement complex (TCC) generation was inhibited as an effect of SMA-CPB (p = 0.047). There was an interaction of SMA-CPB and MPSS to decrease both TCC (p = 0.042) and bradykinin generation (p = 0.028). There were strong effects of MPSS in inhibiting release of interleukin 6 (IL-6) (p = 0.007) and IL-8 (p < 0.001) and tissue plasminogen activator over time (p = 0.009) as well as decreasing peak day 1 creatine kinase (CK, p = 0.015) levels. Clinical effects of MPSS included decreased atrial fibrillation (p = 0.02), improved cardiac index over time, increased pulmonary compliance, and increased insulin need.

Conclusions

This trial suggests a potential beneficial effect for combined strategies to minimize inflammation after CPB. The specific effect of MPSS in decreasing postoperative atrial fibrillation and CK warrants further investigation of its role as a potential myocardial protective agent.

Section snippets

Material and Methods

This clinical trial was approved by the Human Research Ethics Board of the Ottawa Heart Institute. Informed consent was obtained before participation from eligible patients who were scheduled for coronary artery bypass grafting (CABG) on CPB. Exclusion criteria consisted of those patients on steroids or Coumadin and those undergoing emergency, reoperative surgery or other cardiac procedures in addition to CABG. Patients were also excluded if there was evidence of preoperative coagulopathy,

Results

The demographics and the operative characteristics of the patients in each of the four groups are listed in Table 1. Three patients were excluded after randomization but before intervention due to surgeon request and no sampling was done. All other patients (n = 17 per group) completed the study with full follow-up.

Comment

In the face of an increasing number of high risk patients undergoing cardiac surgery, a new paradigm for cardiopulmonary bypass management must be developed with strategies to limit systemic activation by incorporating the best available biocompatible circuits with complementary pharmacologic agents. We [1] and others [6] have demonstrated the thromboresistant properties of SMA-CPB, however its ability to limit inflammation related to systemic activation was less evident. Therefore, we elected

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