Long-Term Propofol Infusion for Refractory Postoperative Nausea

Abstract

Propofol possesses direct antiemetic properties at subanesthetic doses. Low-dose infusions of propofol have been successfully used to treat chemotherapy-induced nausea and vomiting refractory to conventional therapies [1]. Bolus doses of propofol have been effective in treating postoperative nausea and vomiting in the recovery room [2]. Serum samples were not obtained for quantitative propofol analysis in either of these reports. The authors obtained a serum propofol level in a patient with severe postoperative nausea and vomiting who was treated with a subanesthetic propofol infusion for 5 days. Case Report A 43-yr-old woman with metastatic squamous cell carcinoma of the vagina underwent total pelvic exenteration. Her postoperative course was characterized by severe pain that was difficult to manage. Pain relief was ultimately achieved with morphine delivered via patient-controlled analgesia device and transdermal fentanyl. On this analgesic regimen the patient complained of relentless nausea which was refractory to diphenhydramine, promethazine, prochlorperazine, metoclopramide, scopolamine, and ondansetron therapy. These drugs were administered in maximum recommended doses over 3 wk. On postoperative day 21, a therapeutic trial of propofol was begun in the patient's room on the gynecologic oncology ward. A bolus of propofol 0.1 mg/kg followed by a continuous infusion of 1 mg centered dot kg-1 centered dot h-1 resulted in dramatic relief of her nausea without any subjective report of sedation. The propofol infusion was continued for 5 days. Forty-eight hours after propofol infusion was begun, her serum level of propofol was 197 ng/mL. Propofol was prepared as a 0.2% solution in 5% dextrose as per instructions provided in the product package insert. The dilution was made in a 250-mL glass bottle and administered via a locked infusion pump (Abbott Lifecare, North Chicago, IL). Noninvasive arterial oxygen saturation was 97%-99% throughout the duration of the infusion. Arterial blood pressure and respiratory rate were normal while propofol was infused. The patient was not sedated and tolerated enteral feedings during her treatment with propofol. When the propofol infusion was discontinued, nausea and vomiting returned. This was treated with intravenous ondansetron 30 mg every morning and promethazine 25 mg by intramuscular injection every 6 h. Emesis ceased when she was weaned off opiate therapy on the 34th postoperative day. The patient was discharged from the hospital on the 38th postoperative day. Discussion The incidence of nausea and emesis is as high as 46% when morphine is administered via a patient-controlled analgesia system [3]. Conventional antiemetic drugs are usually effective at controlling nausea. When these drugs are not sufficient, more aggressive pharmacologic therapies are warranted. The decision to use propofol in this patient was based on work by Scher et al. [1]. These investigators infused propofol at a dose of 1.0 mg centered dot kg-1 centered dot h-1, after an initial bolus of 0.1 mg/kg, to three young adults with nausea and vomiting associated with chemotherapy of osteogenic sarcoma. All three reported dramatic relief of their nausea. In a randomized, blinded, clinical trial comparing a small bolus dose of propofol to a placebo for the treatment of postoperative nausea and vomiting in the recovery room, Borgeat et al. [2] found propofol significantly more effective that placebo. Neither of these groups reported serum propofol levels as part of their work. Pavlin et al. [4] infused propofol to achieve target levels of 150, 300, and 600 ng/mL and reported all three levels were effective in attenuating alfentanil-induced nausea. These investigators infused propofol for only 1 h at each level. Our observation that a serum propofol level of 197 ng/mL after 48 h of infusion was effective in controlling morphine- and fentanyl-induced nausea corroborates their findings and extends their observations to include long-term propofol infusion. The Cp50 is the plasma drug concentration at which 50% of patients will not respond to a given stimulus. The Cp50 for hypnosis with propofol is 3400 ng/mL [5]. When used for operative anesthesia, there is a marked reduction in the Cp50 for propofol when fentanyl is concommittantly administered [6]. A fentanyl concentration of 3 ng/mL reduces the propofol Cp50 for hypnosis by 40% [6]. At the low propofol levels that appear to be necessary for the treatment of nausea and vomiting, this interaction is unlikely to be clinically significant. We did not observe any increase in sedation in this patient when the propofol infusion was started. Propofol is less expensive than the 5-HT3 antagonist ondansetron. The recommended dose of ondansetron for postoperative nausea and vomiting is 4 mg every 4 h. At $171.19 per 20-mg vial, the cost of one day's therapy with odansetron is $205.43. Propofol costs $82.74 per day at the doses used in the patient described above. The ratio of the cost of ondansetron to that of propofol in 2.48:1. Ondansetron costs over 40% more than propofol. We have described a patient with severe postoperative nausea successfully treated with a subanesthetic infusion of propofol. Propofol is a cost-effective alternative to newer antiemetic drugs for the treatment of refractory postoperative nausea and vomiting.