Chloroprocaine Lavage to Improve Outcomes Related to Operative Cesarean Delivery

Study Overview
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Brief Summary
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The long term objective is to show that intraperitoneal chloroprocaine can be used an alternative option to avoid general anesthesia during cesarean delivery, to alleviate mother's discomfort from surgical pain, reduce complications, and improve the birth experience. The objectives in this study are to determine the amount of chloroprocaine that is absorbed into the blood in order to create a plasma concentration time profile and to determine the incidence of side effects to help guide selection of an appropriate concentration for future study.

Detailed Description
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Compared to general anesthesia, neuraxial anesthesia (spinals and epidurals) is associated with a lower risk for maternal aspiration and airway compromise, exposes the baby to less anesthetic, and allows for greater maternal involvement in the birth process. For these reasons, it has become the preferred method of anesthesia for cesarean delivery. Spinals that are placed to facilitate cesarean delivery have a duration of one to two hours. Currently, if that duration is exceeded patients must have general endotracheal anesthesia. In addition, suboptimal neuraxial anesthesia for cesarean delivery is not uncommon with an incidence of 2-9%, depending upon the urgency of surgery and the type of neuraxial block. Providing less than adequate anesthesia for cesarean delivery may increase the risk of legal liability. For this reason, some patients with suboptimal neuraxial anesthesia have intraoperative conversion to general endotracheal anesthesia. The first known description of the use of intraperitoneal local anesthetic to provide anesthesia for cesarean delivery was published in 1975. In this article Ranney et al. described how to use up to 100 mL of 1% procaine to provide anesthesia for cesarean delivery under local field block alone. Some of this was injected into the skin and fascia, and the remainder was diluted to 0.5% and spilled into the peritoneum. Multiple publications have shown that intraperitoneal local anesthetic can be used to treat intraoperative and postoperative pain, prevent postoperative nausea, and shorten hospital length of stay. A recently published 40-month case series showed that chloroprocaine lavage can be used as part of a multimodal approach to treating intraoperative pain. In this case series, the technique of chloroprocaine lavage helped investigators to avoid general endotracheal anesthesia in 32 women having a cesarean delivery. In this case series, no patients exhibited clinical signs of systemic local anesthetic toxicity. It is believed that chloroprocaine has a limited potential for toxicity because of its short plasma half-life, which is only 11-21 seconds. The purpose of this study is to determine the amount of chloroprocaine that is taken up into the blood stream after intraperitoneal administration to ensure that blood levels are low and do not raise a safety concern. Data obtained from this study will help to define a safe dose of chloroprocaine for intraperitoneal administration.

Official Title
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Chloroprocaine Lavage to Improve Outcomes Related to Operative Cesarean Delivery

Conditions
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Cesarean Section

Intervention / Treatment
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* Drug: Preservative free 1% Chloroprocaine
* Drug: Preservative free 2% Chloroprocaine
* Drug: Preservative free 3% Chloroprocaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects ≥ 18 to 50 years of age having scheduled cesarean sections on 12C (Labor and Delivery) within Oregon Health & Science University (OHSU). Only subjects having spinal anesthesia will be eligible. Only subjects that can have a Pfannenstiel incision will be enrolled. Exclusion Criteria: Subjects with chronic narcotic usage Subjects that are deemed to need a combined spinal epidural for any reason. Subjects who are unable to successfully get a spinal block Subjects with known atypical cholinesterase activity American Society of Anesthesiologist physical status IV or higher Subjects with contraindication to neuraxial anesthesia (coagulopathy, infection) Subjects with stage 4 chronic kidney disease or worse (eGFR < 30 ml/min) Subjects with significant hepatic dysfunction (AST or ALT > 2x the upper limit of normal) Subjects with allergies to drugs required for this protocol. Subjects with multifetal gestations Subjects with a BMI > 40 kg/m2

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Preservative free Chloroprocaine Group 1<br>40 ml of preservative-free 1% chloroprocaine | Drug: Preservative free 1% Chloroprocaine<br>* 40 ml of preservative-free 1% chloroprocaine is planned for administration into the peritoneal cavity after delivery of the baby.<br>* Other names: Nesacaine;|
| Active Comparator: Preservative free Chloroprocaine Group 2<br>40 ml of preservative-free 2% chloroprocaine | Drug: Preservative free 2% Chloroprocaine<br>* 40 ml of preservative-free 2% chloroprocaine is planned for administration into the peritoneal cavity after delivery of the baby.<br>* Other names: Nesacaine;|
| Active Comparator: Preservative free Chloroprocaine Group 3<br>40 ml of preservative-free 3% chloroprocaine | Drug: Preservative free 3% Chloroprocaine<br>* 40 ml of preservative-free 3% chloroprocaine is planned for administration into the peritoneal cavity after delivery of the baby.<br>* Other names: Nesacaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chloroprocaine plasma concentration at 1 minute | The chloroprocaine plasma concentration obtained from a venous sample 1 minute after intraperitoneal chloroprocaine administration. | 1 minute after intraperitoneal chloroprocaine administration | 
| Chloroprocaine plasma concentration at 5 minutes | The chloroprocaine plasma concentration obtained from a venous sample 5 minutes after intraperitoneal chloroprocaine administration. | 5 minutes after intraperitoneal chloroprocaine administration | 
| Chloroprocaine plasma concentration at 10 minutes | The chloroprocaine plasma concentration obtained from a venous sample 10 minutes after intraperitoneal chloroprocaine administration. | 10 minutes after intraperitoneal chloroprocaine administration | 
| Chloroprocaine plasma concentration at 20 minutes | The chloroprocaine plasma concentration obtained from a venous sample 20 minutes after intraperitoneal chloroprocaine administration. | 20 minutes after intraperitoneal chloroprocaine administration | 
| Chloroprocaine plasma concentration at 30 minutes | The chloroprocaine plasma concentration obtained from a venous sample 30 minutes after intraperitoneal chloroprocaine administration. | 30 minutes after intraperitoneal chloroprocaine administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Adverse experience reporting will include the following: seizures, tinnitus, metallic taste, anxiety, agitation, muscle twitching, drowsiness, respiratory depression, dizziness, nausea, vomiting, vision changes, paresthesias, perioral numbness, hypotension, arrhythmias, and cardiac arrest. | Within 4 hours of intraperitoneal chloroprocaine administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chloroprocaine, cesarean delivery, lavage