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. 2016 Jul;117(1):87-94.
doi: 10.1093/bja/aew032.

Skeletal muscle and plasma concentrations of cefazolin during complex paediatric spinal surgery

A S Himebauch  1 , W N Sankar  2 , J M Flynn  2 , M T Sisko  3 , G S Moorthy  4 , J S Gerber  5 , A F Zuppa  6 , E Fox  7 , J P Dormans  8 , T J Kilbaugh  3
Affiliations

Skeletal muscle and plasma concentrations of cefazolin during complex paediatric spinal surgery

A S Himebauch et al. Br J Anaesth. 2016 Jul.

Abstract

Background: Surgical site infections (SSIs) can have devastating consequences for children who undergo spinal instrumentation. Prospective evaluations of prophylactic cefazolin in this population are limited. The purpose of this study was to describe the pharmacokinetics and skeletal muscle disposition of prophylactic cefazolin in a paediatric population undergoing complex spinal surgery.

Methods: This prospective pharmacokinetic study included 17 children with adolescent idiopathic scoliosis undergoing posterior spinal fusion, with a median age of 13.8 [interquartile range (IQR) 13.4-15.4] yr and a median weight of 60.6 (IQR 50.8-66.0) kg. A dosing strategy consistent with published guidelines was used. Serial plasma and skeletal muscle microdialysis samples were obtained during the operative procedure and unbound cefazolin concentrations measured. Non-compartmental pharmacokinetic analyses were performed. The amount of time that the concentration of unbound cefazolin exceeded the minimal inhibitory concentration for bacterial growth for selected SSI pathogens was calculated.

Results: Skeletal muscle concentrations peaked at a median of 37.6 (IQR 26.8-40.0) µg ml(-1) within 30-60 min after the first cefazolin 30 mg kg(-1) dose. For patients who received a second 30 mg kg(-1) dose, the peak concentrations reached a median of 40.5 (IQR 30.8-45.7) µg ml(-1) within 30-60 min. The target cefazolin concentrations for SSI prophylaxis for meticillin-sensitive Staphylococcus aureus (MSSA) and Gram-negative pathogens were exceeded in skeletal muscle 98.9 and 58.3% of the intraoperative time, respectively.

Conclusions: For children with adolescent idiopathic scoliosis undergoing posterior spinal fusion, the cefazolin dosing strategy used in this study resulted in skeletal muscle concentrations that were likely not to be effective for intraoperative SSI prophylaxis against Gram-negative pathogens.

Keywords: cefazolin; microdialysis; paediatric; scoliosis; surgery, spinal.

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Figures

Fig 1
Fig 1
Flow diagram describing study participants. MD, microdialysis; OR, operating room.
Fig 2
Fig 2
Semi-logarithmic concentration–time profile for unbound cefazolin in microdialysate and plasma samples of all patients who received one dose of cefazolin. The horizontal lines indicate various concentration targets and associated surgical site infection pathogen(s). The vertical line indicates 240 min, the time when cefazolin was dosed again for those patients receiving two doses. E., Escherichia; K., Klebsiella; MD, microdialysate; MSSA, meticillin-sensitive Staphylococcus aureus.
Fig 3
Fig 3
Semi-logarithmic concentration–time profile for unbound cefazolin in microdialysate and plasma samples of all patients who received two doses of intraoperative cefazolin. The horizontal lines indicate various concentration targets and associated surgical site infection pathogen(s). The vertical line indicates 240 min, the time when cefazolin was dosed again. E., Escherichia; K., Klebsiella; MD, microdialysate; MSSA, meticillin-sensitive Staphylococcus aureus.
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