Does a Single Intravenous Dose of Ketamine Reduce the Need for Supplemental Opioids in Post-Cesarean Section Patients?

Eligible women for elective cesarean section admitted to the Labor and Delivery Unit of Prentice Women's Hospital will be approached for study participation immediately after the routine preanesthetic evaluation. This occurs shortly after admission to the Labor and Delivery Unit. Women who agree to participate will give written, informed consent at this time.

Subjects will be prepared preoperatively in the usual fashion with intravenous (IV) access, aspiration prophylaxis and intraoperative monitoring. Preincision antibiotics will be given and uterotonic medications will be used as per usual practice after delivery.

The anesthesiologist will perform a spinal anesthetic per routine with the subject in the sitting position using sterile technique at the L3-4 interspace (± one vertebral interspace). The spinal anesthetic will consist of 12 mg of hyperbaric bupivacaine + 15 μg fentanyl + 150 μg of morphine. The subject will be placed supine with left lateral tilt to alleviate aortocaval compression. Cesarean section will commence after adequate anesthesia is assured to a T4 sensory level to pinprick. Vasopressors and IV fluids will be administered at the anesthesiologist's discretion per usual practice.

At the time of delivery, subjects will be randomized to one of two groups using a computer generated random number table. Randomization will be blocked based on whether the cesarean procedure is a primary or a repeat procedure. Randomization assignments will be kept in sequentially numbered opaque envelopes. The envelope will be opened by a research nurse who will prepare a 20 mL syringe labeled "study drug". The syringe will be given to the anesthesiologist blinded to the treatment group who will subsequently administer the study drug. Subjects randomized to the treatment group will receive ketamine 10 mg (ketamine 10 mg/mL) diluted to 20 mL with 0.9% preservative free saline. Subjects randomized to the placebo group will receive 20 mL preservative free saline.

The study drug will be administered into the intravenous line via an infusion pump over 10 minutes. Five minutes after placebo or drug administration, the anesthesiologist will ask the subject if she has nausea, vomiting and pruritus. Nausea and pruritus will be graded as none, mild, moderate or severe; and vomiting as present or absent. Any spontaneous complaints of psychedelic effects will be noted at this time. Sedation will be assessed via the Richmond agitation-sedation scale (RASS \[see Appendix 1\]).

Upon completion of the cesarean section, the subject will be transported to the post anesthesia recovery unit. Patients will receive ketorolac 30 mg every 6 hours time 4 doses beginning shortly after admission to the PACU.

At 1 h, 4 h, 8 h, 12 h and at 24 h after administration of the study drug, the subject's pain will be assessed using the numeric rating scale for pain NRS 0-10 (see Appendix 2). Patients may request rescue analgesia if they are experiencing discomfort. The time of first rescue analgesia request will be noted, and the NRS will be determined at the time of request for rescue analgesia.

Rescue medication will consist of hydrocodone 10 mg plus acetaminophen 325 mg per os. An additional dose of hydrocodone 10 mg plus acetaminophen 325 mg will be provided after 1 hour if the pain is not relieved to the subject's satisfaction. These are routine oral analgesic medications for postoperative cesarean delivery analgesia. Standard orders will be written for monitoring sedation and respiratory rate, and treatment of side effects (nausea, vomiting, pruritus and respiratory depression). The total amount of rescue medication will be determined for each subject after 24, 48 and 72 hours.

The presence of nausea, vomiting, and pruritus will be assessed at the same time intervals as the NRS for pain: 1 h, 4 h, 8 h, 12 h and 24 h after IV infusion of ketamine or placebo. The subjective psychedelic effects of ketamine and morphine will be assessed using a set of true/false questions from the LSD and morphine short form of the Addiction Research Center Inventory, ARCI (Appendix 3). These questions will be administered verbally by the anesthesiologist or researcher blinded to the treatment group upon admission to the PACU and at 4 h.

The following data will be collected in addition to the primary and secondary outcome data: maternal age, height, weight, prepregnancy weight, gestational age and IV fluids administered during cesarean section. In addition, all intraoperative and postoperative medications will be recorded, including those administered for the treatment of side effects listed above.

Protocol specific analgesia assessment ends 24 hours after administration of the study drug. At 72 hours the subject will be asked about her satisfaction with postoperative analgesia (100 mm scale, 0 mm = not satisfied at all, 100 mm = very satisfied). One telephone follow-up evaluation 2 weeks after delivery will again, assess for satisfaction with analgesia and average pain (NRS) since the procedure.