Pharmacokinetics of 2 mg/kg Bupivacaine in a Rectus Abdominis Sheath Block in Horses.

Overview

• This study investigated how a dose of 2 mg/kg of bupivacaine behaves in the body (pharmacokinetics) when used in a rectus abdominis sheath (RAS) block in horses, focusing on the risk of local anesthetic toxicity.

Background

• Bupivacaine is a local anesthetic commonly used to block pain.
• In horses, the rectus abdominis sheath (RAS) block is a regional anesthesia technique aimed at numbing the abdominal wall area.
• Administering large volumes of bupivacaine can pose a risk of toxicity, manifesting in dangerous neurological or cardiac effects.
• Understanding the pharmacokinetics of bupivacaine in this context helps determine safe dosing and guide clinical use.

Study Design and Methods

• Subjects: Six healthy adult horses were used for the experiment.
• Intervention: Each horse was sedated with xylazine, a sedative drug.
• Bupivacaine Dose: 2 mg per kg of body weight was administered via an ultrasound-guided bilateral 2-point RAS block.
• Sampling: Blood plasma samples were taken before injection (baseline) and then repeatedly from 5 minutes up to 24 hours after injection.
• Analysis was conducted using liquid chromatography-tandem mass spectrometry, a sensitive method to quantify drug levels in plasma.
• Pharmacokinetic parameters were calculated using noncompartmental analysis including:
  • Cmax (maximum plasma concentration observed)
  • Tmax (time to reach the maximum concentration)
  • Terminal half-life (time for plasma concentration to reduce by half in the terminal phase)
  • Area under the plasma concentration-time curve (AUC), representing overall drug exposure
  • Percentage of AUC extrapolated beyond the 24-hour sampling period

Key Findings

• Maximum concentration (Cmax) of bupivacaine in plasma ranged from 38.4 to 151.8 ng/mL across horses.
• The time to reach maximum concentration (Tmax) ranged between 1.5 to 4 hours after injection.
• The terminal half-life varied widely from 9.2 to 46 hours, indicating prolonged drug presence in the blood for some horses.
• AUC values ranged from 1351.9 to 2463.3 h·ng/mL, which represent the total systemic exposure to the drug.
• The percentage of AUC extrapolated (due to sampling stopping at 24 hours) was quite variable, from 8.6% up to 61.4%, suggesting incomplete capture of the drug elimination phase within the sampling timeframe.
• One plasma sample showed bupivacaine levels similar to those known to cause neurotoxicity in humans; however, this was considered an outlier and not typical of the group.

Interpretation and Implications

• The pharmacokinetic profile showed significant inter-horse variability in absorption and elimination.
• The relatively high percentage of extrapolated AUC suggests the 24-hour monitoring period was insufficient to accurately estimate terminal half-life and total drug exposure for some horses.
• Although generally safe at the 2 mg/kg dose in this study, the presence of a neurotoxic level outlier signals the importance of caution.
• Further studies, especially in anesthetized horses undergoing abdominal surgery (e.g., colic surgery), are necessary to fully assess safety and toxicity risks under more clinically relevant conditions.
• This study informs veterinary anesthesiologists about the pharmacokinetics of bupivacaine delivered via RAS block and highlights the need for extended monitoring or alternative dosing adjustments before routine clinical application.