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Skeletal muscle and plasma concentrations of cefazolin during cardiac surgery in infants
Adam S Himebauch1, Susan C Nicolson2, Martha Sisko2
1Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa; Center for Clinical Pharmacology, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa.
Insights
Cefazolin dosing in pediatric cardiac surgery achieved muscle concentrations effective against Staphylococcus aureus but not gram-negative pathogens. Deep hypothermic circulatory arrest impacted cefazolin levels, reducing effectiveness.
Area of Science:
- Pharmacology
- Pediatric Surgery
- Infectious Disease
Background:
- Skeletal muscle drug concentrations are crucial for surgical site infection prophylaxis.
- Cefazolin is a common prophylactic antibiotic in cardiac surgery.
- Understanding cefazolin pharmacokinetics in pediatric cardiac surgery is essential for optimizing dosing.
Purpose of the Study:
- To determine cefazolin pharmacokinetics and tissue disposition in pediatric patients undergoing cardiac surgery.
- To evaluate cefazolin skeletal muscle concentrations in relation to prophylactic goals.
Main Methods:
- 12 pediatric patients undergoing cardiac surgery were studied.
- Cefazolin was administered at standard doses (25 mg/kg).
- Plasma and skeletal muscle microdialysis samples were collected for unbound cefazolin concentration analysis.
Main Results:
- Skeletal muscle cefazolin concentrations peaked within 30-38.5 minutes after the initial dose.
- Deep hypothermic circulatory arrest delayed peak concentrations and reduced overall skeletal muscle exposure.
- Concentrations exceeded targets for methicillin-sensitive Staphylococcus aureus but were insufficient for gram-negative pathogens.
Conclusions:
- The standard cefazolin dosing strategy provides adequate skeletal muscle concentrations against methicillin-sensitive Staphylococcus aureus in infants.
- This strategy is likely ineffective for prophylaxis against gram-negative pathogens in this population.
- Deep hypothermic circulatory arrest significantly alters cefazolin tissue disposition.
Objective:
To describe the pharmacokinetics and tissue disposition of prophylactic cefazolin into skeletal muscle in a pediatric population undergoing cardiac surgery.
Methods:
The subjects included 12 children, with a median age of 146 days (interquartile range, 136-174) and median weight of 5.5 kg (interquartile range, 5.2-7.3) undergoing cardiac surgery and requiring cardiopulmonary bypass with or without deep hypothermic circulatory arrest. Institutional cefazolin at standard doses of 25 mg/kg before incision and 25 mg/kg in the bypass prime solution were administered. Serial plasma and skeletal muscle microdialysis samples were obtained intraoperatively and the unbound cefazolin concentrations measured. Noncompartmental pharmacokinetic analyses were performed and the tissue disposition evaluated.
Results:
After the first dose of cefazolin, the skeletal muscle concentrations peaked at a median microdialysis collection interval of 30 to 38.5 minutes. After the second dose, the peak concentrations were delayed a median of 94 minutes in subjects undergoing deep hypothermic circulatory arrest. Skeletal muscle exposure to cefazolin measured by the area under concentration time curve 0-last measurement was less in the subjects who underwent deep hypothermic circulatory arrest than in those who received cardiopulmonary bypass alone (P = .04). The skeletal muscle concentrations of cefazolin exceeded the goal concentrations for methicillin-sensitive Staphylococcus aureus prophylaxis; however, the goal concentrations for gram-negative pathogens associated with surgical site infections were achieved only 42.1% to 84.2% and 0% to 11.2% of the intraoperative time in subjects undergoing cardiopulmonary bypass alone or deep hypothermic circulatory arrest, respectively.
Conclusions:
This cefazolin dosing strategy resulted in skeletal muscle concentrations that are likely not effective for surgical prophylaxis against gram-negative pathogens but are effective against methicillin-sensitive S aureus in infants undergoing cardiac surgery.
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