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Literature Review

Impact of Intraoperative Continuous-Infusion Versus Intermittent Dosing of Cefazolin Therapy on the Incidence of Surgical Site Infections After Coronary Artery Bypass Grafting

Shoulders BR, Crow JR, Davis SL, et al. Pharmacotherapy. 2016;36(2):166-173.

Reviewers: David J. Brenneman, MD MBA1; Yong G. Peng, MD PhD FASE1

  1. Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL
Background

Surgical site infection (SSI) status post–coronary artery bypass grafting surgery (CABG) is a low-incidence complication that can be associated with high morbidity. Intermittent (INT) bolus dosing results in lower serum and tissue concentrations of cefazolin than comparable continuous infusion (CI) administrations, but outcomes have not been investigated.

Methods

This study was a retrospective, quasi-experimental cohort study performed between June 2013 and December 2014 at a tertiary care center as they implemented a new CI protocol. INT data was collected from patient encounters between June 2013 and February 2014. CI data was collected between April 2014 and December 2014. The INT protocol was 2 grams for patients weighing fewer than 120 kg and 3 grams for patients weighing more than 120 kg and repeating every 2 hours. The CI protocol was a bolus of 2 or 3 grams based on weight followed by a 1 gram per hour infusion that was to be adjusted for creatinine clearance.

Results

There was no significant difference between the two groups regarding SSI (1.7% vs 4.6%, P=.116). There was a reduction in superficial SSI in the CI group (0.4% vs 2.8%, P=.039) and saphenous vein site infections approached significance (0% vs 1.4%, P=.07).

On the INT arm, 284 patients were included and on the CI arm, 232 patients. Eighty-seven patients were excluded from the CI arm for inadvertent intermittent bolus dosing. Diabetes (P=.001), corticosteroid usage (P=.003), and peripheral arterial disease (PAD) were selected by univariate analysis as risk factors for SSI. PAD was eliminated during stepwise multivariate analysis. This analysis suggested that CI cefazolin decreased odds of SSI by 66%, but this finding was not significant.

There was no difference in safety profile, including postoperative dialysis (1.7% vs 0.7%, P=.598) or seizures (0% vs 1.1%, P=.116). 

Subgroup analysis showed that when protocol nonadherence occurred, INT was usually dosed with reduced frequency and CI was dosed without adjustment for renal impairment.

Conclusion

Cefazolin by CI reduces the risk of superficial SSI after CABG. Diabetes and corticosteroids are risk factors for SSI. CI cefazolin was not associated with increased risk of seizures or dialysis. 

Comments

CABG is a common procedure, and SSI is a complication with a low incidence but potential for high morbidity and mortality. Cardiopulmonary bypass increases SSI through activation of systemic inflammatory response syndrome, exposure of blood to extracorporeal surfaces, and alterations in pharmacokinetics and pharmacodynamics. Tissue cefazolin concentrations may remain more consistently above the minimum inhibitory concentration with continuous administration of cefazolin compared to intermittent bolus dosing during cardiopulmonary bypass. This study investigated the patient-centered impact of CI cefazolin, compared to traditional INT dosing. Continuous infusion cefazolin may reduce the risk of superficial surgical site infections; however, there was no significant reduction in the overall risk of SSI. 

There were limitations in the design of this study. First, the CI cohort systematically received a larger dose of cefazolin per unit time, according dosing protocols for each group. This was corroborated by the investigators’ findings. The effect of CI may be difficult to separate from the effect of increased dose with regard to the impact on SSI. Moreover, the impact of protocol nonadherence in subgroup analysis was identified to cause relative overdosing in the CI group and relative underdosing in INT, further contributing to the disparity in net cefazolin administration between the two cohorts. 

A second limitation of this study is the potential for selection bias inherent to the study design. Eighty-seven patients were excluded from the CI cohort because of inadvertent INT dosing of cefazolin. There also was a higher incidence of congestive heart failure, diabetes, and combined bypass and valve surgery in the CI group, further contributing to incongruity between the two groups.

A third limitation is that the study was underpowered. Had more subjects been included, the authors may have been able to make more robust claims about overall SSI, saphenous vein site infection, odds ratio of CI, and the contribution of PAD to SSI. Further study with a larger population is necessary to elucidate the above-discussed deficiencies. 

A final limitation of this study is the lack of description of important details relevant to SSI that were not recorded by the authors. The authors could not comment on confounding surgical, medical, and infection control interventions at the same time as this study in their institution. The authors did not comment on the impact of unilateral or bilateral internal mammary artery graft usage on wound infection. Moreover, the authors did not comment on anesthesiologists’ and surgeons’ contribution, and if providers contributed proportionally similar care to the INT and CI cohorts.