Pharmacokinetics a>nd Tolerability of Intraperitoneal Chloroprocaine After Fetal Extraction in Women Undergoing Cesarean Delivery

Abstract

BACKGROUND: Intraperitoneal chloroprocaine has been used during cesarean delivery to supplement suboptimal neuraxial anesthesia for decades. The short in vitro half-life of chloroprocaine (11-21 seconds) has been cited to support the safety of this approach. However, there are no data regarding the rate of absorption, representing patient drug exposure, through this route of administration. Accordingly, we designed a study to determine the in vivo half-life of intraperitoneal chloroprocaine and assess clinical tolerability. METHODS: We designed a single-center, prospective, cohort, multiple-dose escalation study of women 18 to 50 years of age undergoing cesarean delivery with spinal anesthesia. Chloroprocaine (40 mL) was administered after delivery of the newborn and before uterine closure. The first cohort (n = 5) received 1%, the second cohort (n = 5) received 2%, and the third cohort (n = 5) received 3% chloroprocaine solution. Maternal blood samples were obtained before administration and 1, 5, 10, 20, and 30 minutes after dosing. The primary objective was to define the pharmacokinetic profile of intraperitoneal chloroprocaine, including in vivo half-life. The secondary objective was to evaluate tolerability through determination of peak plasma concentration and prospective assessment for local anesthetic systemic toxicity. RESULTS: The peak plasma concentration occurred 5 minutes after intraperitoneal administration in all 3 cohorts: 64.8 ng/mL (6.5 µg/kg), 28.7 ng/mL (2.9 µg/kg), and 799.2 ng/mL (79.9 µg/kg) for 1%, 2%, and 3% chloroprocaine, respectively. The in vivo half-life of chloroprocaine after intraperitoneal administration was estimated to be 5.3 minutes (95% confidence interval, 4.0-6.6). We did not detect clinical signs of local anesthetic systemic toxicity in any of the 3 cohorts. CONCLUSIONS: The in vivo half-life of intraperitoneal chloroprocaine (5.3 minutes) is more than an order of magnitude greater than the in vitro half-life (11-21 seconds). However, maximum plasma concentrations of chloroprocaine (C max range, 0.05-79.9 µg/kg) were not associated with local anesthetic systemic toxicity and remain well below our predefined safe level of exposure (970 µg/kg) and levels associated with clinical symptoms (2.6-2.9 mg/kg). Therefore, our study suggests that intraperitoneal chloroprocaine, in a dosage ≤1200 mg, administered after fetal extraction, is well tolerated during cesarean delivery. (Anesth Analg 2022;135:777-86) KEY POINTS• Question: Based on pharmacokinetic and tolerability data, should intraperitoneal chloroprocaine continue to be used to supplement suboptimal neuraxial anesthesia in women undergoing cesarean delivery? • Findings: In this prospective cohort study of 15 women who received intraperitoneal chloroprocaine during cesarean delivery, the peak plasma concentration was 799.2 ng/mL (79.9 µg/kg), the time of maximum concentration was 5 minutes, and the half-life was 5.3 minutes, without clinical signs of local anesthetic systemic toxicity. • Meaning: The pharmacokinetic and tol...