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Pharmacokinetics of an intravenous constant rate infusion of a morphine-lidocaine-ketamine combination in Holstein calves undergoing umbilical herniorrhaphy

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  • 1 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 2 2Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.
  • | 3 3Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

Abstract

OBJECTIVE

To describe the pharmacokinetics of morphine, lidocaine, and ketamine associated with IV administration of a constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination to calves undergoing umbilical herniorrhaphy.

ANIMALS

20 weaned Holstein calves with umbilical hernias.

PROCEDURES

Calves were randomly assigned to receive a CRI of an MLK solution (0.11 mL/kg/h; morphine, 4.8 μg/kg/h; lidocaine, 2.1 mg/kg/h; and ketamine, 0.42 mg/kg/h) for 24 hours (MLK group) or 2 doses of flunixin meglumine (1.1 mg/kg, IV, q 24 h) and a CRI of saline (0.9% NaCl) solution (0.11 mL/kg/h) for 24 hours (control group). For all calves, the CRI was begun after anesthesia induction. Blood samples were obtained immediately before and at predetermined times for 120 hours after initiation of the assigned treatment. Noncompartmental analysis was used to estimate pharmacokinetic parameters for the MLK group.

RESULTS

During the CRI, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine. Mean terminal half-life was 4.1, 0.98, and 1.55 hours and area under the concentration-time curve was 41, 14,494, and 7,426 h•μg/mL for morphine, lidocaine, and ketamine, respectively. After the CRI, the mean serum drug concentration at steady state was 6.3, 616.7, and 328 ng/mL for morphine, lidocaine, and ketamine, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE

During the CRI of the MLK solution, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine, likely owing to the fairly long half-life of morphine. Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols.

Abstract

OBJECTIVE

To describe the pharmacokinetics of morphine, lidocaine, and ketamine associated with IV administration of a constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination to calves undergoing umbilical herniorrhaphy.

ANIMALS

20 weaned Holstein calves with umbilical hernias.

PROCEDURES

Calves were randomly assigned to receive a CRI of an MLK solution (0.11 mL/kg/h; morphine, 4.8 μg/kg/h; lidocaine, 2.1 mg/kg/h; and ketamine, 0.42 mg/kg/h) for 24 hours (MLK group) or 2 doses of flunixin meglumine (1.1 mg/kg, IV, q 24 h) and a CRI of saline (0.9% NaCl) solution (0.11 mL/kg/h) for 24 hours (control group). For all calves, the CRI was begun after anesthesia induction. Blood samples were obtained immediately before and at predetermined times for 120 hours after initiation of the assigned treatment. Noncompartmental analysis was used to estimate pharmacokinetic parameters for the MLK group.

RESULTS

During the CRI, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine. Mean terminal half-life was 4.1, 0.98, and 1.55 hours and area under the concentration-time curve was 41, 14,494, and 7,426 h•μg/mL for morphine, lidocaine, and ketamine, respectively. After the CRI, the mean serum drug concentration at steady state was 6.3, 616.7, and 328 ng/mL for morphine, lidocaine, and ketamine, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE

During the CRI of the MLK solution, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine, likely owing to the fairly long half-life of morphine. Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols.

Contributor Notes

Dr. Hartnack's present address is Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843.

Dr. Coetzee's present address is Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

Dr. Kleinhenz's present address is Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

Address correspondence to Dr. Hartnack (ahartnack@tamu.edu).