Pulse Low Dose Steroids Attenuate Post-Cardiopulmonary Bypass SIRS; SIRS I

doi:10.1016/j.jss.2006.02.013

Journal of Surgical Research

Volume 132, Issue 2, 15 May 2006, Pages 188-194

https://doi.org/10.1016/j.jss.2006.02.013 Get rights and content

Background

Cardiopulmonary bypass (CPB) initiates inflammation that contributes to multiorgan dysfunction (SIRS). Steroids have been demonstrated to attenuate this response; however, resistance to use steroids remains because of potential adverse effects of the high doses used. This study examines a lower dose steroid protocol for safety and attenuation of SIRS.

Methods

Sixty patients undergoing CPB were randomized to pulse low doses of methylprednisolone (250 mg given twice IV) or placebo in this RCT. Outcomes pertaining to hemodynamics, ventilator requirement, arrhythmia, and metabolic derangements were recorded. Post-operative glucose control and gastrointestinal prohylaxis was instituted in all patients.

Results

IL-6 concentrations were lower in the steroid group at 4 and 8 h post-operatively (P < 0.0001). The steroid group demonstrated more normothermia (37.2°C versus 37.6°C, P = 0.002), better hemodynamic stability with less requirement for inotropes or vasopressors (0% versus 27.6%, P = 0.005), higher SVRIs (1840 versus 1340 DSm²/cm⁵, P = 0.002), and higher mean arterial pressures (79 versus 74 mmHg, P = 0.03). The steroid group had a shorter duration of intubation (7.7 versus 10.7 h, P = 0.02), a shorter length of ICU stay (1.0 versus 2.0 days, P = 0.03), and less blood loss (505 versus 690 ml, P = 0.04) with no difference in post-operative blood glucose levels or complications.

Conclusions

Patients undergoing cardiopulmonary bypass receiving low pulse dose steroids had better hemodynamics, shorter mechanical ventilation times, less blood loss, and required less time in the ICU compared to those receiving placebo. Therefore, this study demonstrates that prophylactic low dose steroids attenuate the SIRS response to CPB without resulting in any untoward side-effects.

Introduction

Cardiopulmonary bypass (CPB) initiates a systemic inflammatory response characterized by both cell and protein activation [1, 2, 3]. Platelets, neutrophils, monocytes, macrophages, coagulation, fibrinolytic, and kallikrein cascades all take part in what results in increased endothelial permeability, vascular, and parenchymal damage [4, 5, 6, 7]. The inflammatory reaction may contribute to the development of post-operative complications including myocardial dysfunction, respiratory failure, renal and neurological dysfunction, bleeding disorders, altered liver function and ultimately, multiple organ failure. Although most patients convalesce normally post cardiac surgery, all patients are thought to experience these effects to some degree. In an attempt to minimize the deleterious effects of CPB, investigators have attempted a variety of strategies in cardiac surgery ranging from the complete avoidance of CPB [8, 9, 10], to the use of biocompatible circuits [11] and pharmacologic agents to abrogate the systemic response [5, 12, 13, 14, 15, 16, 17]. Investigators have consistently demonstrated the efficacy of steroids as the most potent anti-inflammatory agent for use during CPB [5, 6, 12, 13, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47]. This literature has been well summarized in several reviews [4, 48]. From the available evidence, the 2004 AHA guidelines for coronary artery bypass grafting (CABG) “support liberal prophylactic use in patients undergoing extracorporeal circulation” [49].

However, surgeons remain resistant to adopt the routine use of pulse dose steroids before cardiopulmonary bypass. This stems from the absence of a sufficiently powered randomized controlled trial (RCT) demonstrating clinical benefit. Furthermore, the doses of steroid used in this field have traditionally been very high (30 mg/kg methylprednisolone) and there is concern of wound, infectious, or gastrointestinal (GI) complications.

Complications of steroids are known to be dose dependant. Our 1995 study was the first prospective trial to demonstrate effectiveness of a low dose pulse steroid protocol in suppression of cytokine release and post-operative vasodilation and pyrexia in CABG patients [5]. We propose a study of low pulse dose protocol of methylprednisolone in all on-pump patients undergoing any cardiac surgery including those with diabetes. We further propose that the addition of a strict insulin protocol as well as GI prophylaxis will enhance the safety of this treatment. This study, entitled Steroids In caRdiac Surgery (SIRS I), prospectively examines the effect of low pulse dose methylprednisolone on the release of IL-6 and relevant clinical outcomes after CPB.

Does the relatively low dose of 250 mg Methylprednisolone administered preoperatively and on CPB alter the expression of inflammatory mediators?

We hypothesize that low dose of methylprednisolone suppresses pro-inflammatory mediators in patients undergoing cardiac surgical procedures with CPB.

A randomized, controlled, single-center, blinded trial of 250 mg IV methylprednisolone given twice against placebo.

Section snippets

Methods

This RCT was approved by our local Research Ethics Board. From April 1, 2004, to February 28, 2005, 60 patients were screened and randomized into the study. Inclusion criteria were the provision of informed consent, age greater than 18 years, and a cardiac surgical procedure requiring CPB. Exclusion included the use of systemic steroids, history of bacterial or fungal infection in the last 30 days, or steroid intolerance.

Block randomization via a computer-generated sequence was performed on the

Results

Sixty patients were successfully randomized into the two study groups with no withdrawals. A single patient was unblinded at the request of the family after a poor surgical outcome (paraplegia). This patient was in the steroid group and died of sepsis after 243 days in the ICU. Table 3 summarizes the patient characteristics by study group for which no statistically significant difference was found.

Discussion

The SIRS I trial demonstrates that low dose pulse steroids attenuates the post-operative inflammatory response to cardiopulmonary bypass. This resulted in better hemodynamics, shorter duration of ventilation, less blood loss, more normothermia, and ultimately shorter ICU length of stay. Furthermore, the results suggest that the addition of GI prophylaxis and a rigorous glucose control protocol may abrogate potential adverse effects of steroids. To our knowledge, this is the first RCT to examine

Acknowledgments

The authors would like to acknowledge: Cardiac surgeons of HHSC, Department of anesthesia and perfusion of HHSC, ICU staff of HHSC, and Kim Hall of Clinical Research and Clinical Trials Laboratory.