Subcutaneous Naloxone for the Prevention of Intrathecal Morphine-induced Pruritus in Elective Cesarean Delivery

studying 18 rats that were exposed, in cohorts of 6, to 2 different doses of epidural ondansetron (10mcg or 20mcg) or normal saline. The rats showed neither neurologic signs nor histologic evidence of any spinal cord damage. Questions can certainly be raised about the choice of study animal, the dosages of study drug employed when seeking to exclude neurotoxicity, the number of animals studied, and so on. The authors, however, have adroitly forestalled criticism of this aspect of their study by pointing out that ondansetron is stable and possesses an osmolarity of 270mOsm/L with a pH of 4.6 and a pKa of 7.4. These physicochemical characteristics are about the same as lidocaine with epinephrine. The commercial preparation of ondansetron used in the study (Zofran) does not contain preservatives. Although these facts should not lead clinicians to assume that possession of a similar set of physicochemical characteristics obviates the need to undertake animal studies before human exposure, it may limit the need for large-scale animal studies to prove safety. In the clinical portion of the study, subjects in both groups received IV ondansetron (4mg) after delivery of the fetus and immediately before randomization. After the surgery had concluded, the women received a 48-hour IV infusion of a study solution either IV or epidurally.Women in the IV group, received a baseline infusion, over 48 hours, of ondansetron (8mg in 1L of normal saline) at a rate of 21mL/h and a simultaneous epidural infusion ofmorphine sulfate, 7mg diluted in 100-mL ropivacaine 0.3%. Epidural group subjects had the 48-hour IV infusion limited to placebo saline diluted in 1 liter of normal saline administered at the same rate as in the IV group, and the simultaneous epidural infusion of morphine and ropivacaine with the addition of ondansetron 8mg. The investigators thereby evaluated the drug, the route of administration of the drug, the concentration of that drug, and the duration of exposure to the drug. All in all, a welldesigned protocol. All outcome variables (nausea, vomiting, pruritus, pain) were evaluated using 4-point scales. Pruritus was evaluated as: 0 (no pruritus); 1 (mild pruritus not requesting pharmacologic rescue); 2 (moderate pruritus requesting pharmacologic rescue); 3 (severe pruritus resistant to pharmacologic therapy). Interestingly, none of the study subjects rated their pain as a 3 or 4, and only 10% (IV group) to 15% (epidural group) rated their postoperative pain as mild. Is this a validation of the management techniques utilized in the study or a testimony to the stoicism of the Korean study subjects? The results were clear, however. The women who received epidural ondansetron—in addition to the IV ondansetron 4mg administered after delivery of the infant—experienced significantly less nausea and pruritus than those who did not. This result clearly warrants further investigation.