An Evaluation of Intraabdominal Chloroprocaine During Cesarean Delivery and Its Effect on Postoperative Pain and Nausea; a Randomized Controlled Trial & Pharmacokinetic-pharmacodynamics (PKPD) Analysis.

Postoperative pain relief is an important consideration during and after cesarean section. Although many different methods have been described for proper pain relief, it remains not sufficient and satisfactory in some patients.1,2 The overprescribing of opioids has reached a critical level worldwide, and cesarean section may be the trigger for long-term opioid use in many patients.1,2,3 The optimal strategy for perioperative pain control consists of multimodal therapy to minimize the need for opioids, with the goals of perioperative pain management being to relieve suffering, achieve early mobilization after surgery, reduce length of hospital stay, and achieve patient satisfaction. Currently, most obstetricians use a combination of opioids and NSAIDs for pain control postpartum. These pain control regimens take into account medical, psychological, and physical condition of women, age, level of fear or anxiety, allergies and personal preference at the time of cesarean section. Due to several aspects such as maternal and neonatal wellbeing, postoperative pain relief in cesarean delivery is crucial. Therefore, providing a proper regimen with very quick onset of action, devoid of renal or gastrointestinal complications, and devoid of complications of neonatal abstinence syndrome (NAS) becomes necessary.

Local anesthetics have been extensively used at the time of cesarean section. Chloroprocaine (Nesacaine) is an ester-type local anesthetic (active ingredient - benzoic acid, 4-amino-2-chloro-2-(diethylamino) ethyl ester, monohydrochloride that has been used as an anesthetic and analgesic in obstetrics & gynecology. It has a rapid onset time of action (usually within 6 to 12 minutes; 9.6 min ± 7.3 min at 40 mg dose; 7.9 min ± 6.0 min at 50 mg dose) and a motor block action lasting for 40 minutes to 2 hours.4 Chloroprocaine, like other local anesthetics, blocks the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers.

The rate of intra-abdominal chloroprocaine absorption is dependent upon the total dose and concentration administered and the presence or absence of epinephrine in the anesthetic injection. Epinephrine usually reduces the rate of absorption and plasma concentration of local anesthetics and is sometimes added to local anesthetic injections in order to prolong the duration of action. Various pharmacokinetic parameters of chloroprocaine can be significantly altered by the presence of hepatic or renal disease, addition of epinephrine, factors affecting urinary pH, renal blood flow, and the age of the patient. Chloroprocaine is rapidly metabolized in plasma by hydrolysis of the ester linkage by pseudocholinesterase. The hydrolysis of chloroprocaine results in the production of ß-diethylaminoethanol and 2-chloro-4-aminobenzoic acid, which inhibits the action of the sulfonamides. The kidney is the main excretory organ for chloroprocaine and its metabolites. Urinary excretion is affected by urinary perfusion and factors affecting urinary pH. Due to its short duration of action, favorable safety profile, and very low toxicity, it has been used extensively for spinal anesthesia at the time of cesarean section.5,6 It has also been used for skin infiltration to reduce pain post cesarean section in patients who cannot receive spinal analgesia due to contraindications.7 However, despite its advantages as an analgesic and anesthetic, it has never clinically evaluated to be used intra-abdominally at the time of cesarean section. Although its occasional use has been considered and employed in certain clinical circumstances, clinical evaluation has not been attempted.

The goal of this study is to employ a well-designed randomized controlled clinical trial to compare the efficacy of intraabdominal chloroprocaine administration versus placebo (sterile saline) for pain control at the time of cesarean section. The investigators hypothesize that intra-abdominal chloroprocaine administration at the time of cesarean delivery is associated with decreased postoperative pain and nausea compared to non-administration of chloroprocaine. Patients admitted for cesarean section and meeting inclusion criteria will be approached for consent. Consented patients will then be randomized into two groups.

Group 1: (intraabdominal chloroprocaine administration): These participants will have intraabdominal chloroprocaine administration at the time of cesarean section before fascial closure.