Propofol Is Effective in Chemotherapy-Induced Nausea and Vomiting: A Case Report with Quantitative Analysis (1999)

Nausea and vomiting are the most distressing and unpleasant side effects of cancer chemotherapy during cisplatin-based regimens (1). Selective serotonin antagonists decrease in cisplatin-induced nausea and vomiting (2). However, in some patients, chemotherapy-induced nausea and vomiting are inadequately controlled by antiemetic drugs, including serotonin antagonists, and additional treatment is required. Subhypnotic doses, i.e., 1 mg · kg−1 · h−1, as a continuous IV infusion of propofol, prevent chemotherapy-induced nausea and vomiting (3–5). However, the serum levels of propofol were not measured for quantitative propofol analysis in any of the above reports. We measured the serum propofol level in a patient who had severe chemotherapy-induced nausea and vomiting, who was successfully treated, without a sedative effect, by a continuous infusion of propofol. Case Report A 68-yr-old, 50-kg man with a recurrent carcinoma of the tongue received a 1-day course of cisplatin chemotherapy (50 mg/m2). His history of chemotherapy was consistently complicated by multiple episodes of nausea and vomiting, unrelieved by various antiemetic drugs. A second course of chemotherapy was started 7 wk after the first course. Despite IV administration of granisetron 2 mg, a serotonin antagonist, as antiemetic prophylaxis, the patient complained of severe nausea and vomiting 24 h after initiation of chemotherapy, and he had no appetite. At this stage, we were consulted. Thirty hours after initiation of chemotherapy, a bolus of propofol 0.2 mg/kg followed by a continuous infusion of 1 mg · kg−1 · h−1 resulted in relief of his nausea. Immediately after the administration of propofol, he fell asleep but was easily awakened by verbal command. The infusion rate was decreased by 0.1 mg · kg−1 · h−1 every 30 min. We simulated the predicted blood concentrations of propofol based on the pharmacokinetic variables described by Gepts et al. (6), using a computer simulation program (Propofol Mon 2.2 obtained from M. Nakao, MD, Department of Anesthesiology, Chuden Hospital, Chugoku Electric Power Co. Inc., Hiroshima, Japan). When the predicted concentration was 290 ng/mL at the infusion rate of 0.6 mg · kg−1 · h−1, the patient began complaining of mild nausea. The blood concentration of propofol measured by liquid chromatography was 211 ng/mL. The propofol infusion was continued for about 8 h. During the infusion, the arterial blood pressure and respiratory rate were stable, and noninvasively measured arterial oxygen saturation was 95%–97%. The patient was not sedated and regained his appetite after 2 days. The patient began complaining of severe nausea again within 1 h after the propofol infusion was discontinued. After 24 hours of the first propofol treatment, the patient was given propofol 0.2 mg/kg as an IV bolus followed by a continuous infusion of 0.5 mg · kg−1 · h−1. A decrease in nausea was reported, although mild nausea persisted throughout the infusion. Discussion Subhypnotic doses of propofol exert direct antiemetic effects (7). Schulman et al. (8) showed that a serum propofol level of 197 ng/mL controlled morphine- and fentanyl-induced nausea refractory to various antiemetics. Borgeat et al. (4,5) and Scher et al. (3) reported that propofol in a subanesthetic infusion, i.e., 1 mg · kg−1 · h−1, was effective in preventing chemotherapy-induced nausea and vomiting. However, none of these reports examined the serum propofol levels or attempted to reduce the infusion rate when the patients experienced relief. Our finding that a serum propofol level of 211 ng/mL was effective in relieving chemotherapy-induced nausea and vomiting led to the infusion rate of propofol for the treatment of chemotherapy-induced nausea and vomiting in oncology patients. The mechanism underlying the antiemetic action of propofol is unclear. Nausea and vomiting associated with cisplatin chemotherapy are closely correlated with the peak urinary serotonin metabolite levels (9). Wilder-Smith et al. (10) demonstrated that the urinary serotonin metabolite excretion, after induction of cisplatin chemotherapy, was not inhibited by propofol infusion. Appadu and Lambert (11) showed that propofol was unlikely to interact directly with 5-HT3 receptors in vitro using N1E-115 neuroblastoma cells, and Borgeat (12) explained the synergistic antiemetic effect of propofol with a serotonin antagonist. However, in the patient examined here, propofol did not seem to exert its antiemetic effect by interaction with a serotonin antagonist, because propofol was infused more than 24 h after prophylactic administration of a serotonin antagonist. Perhaps hypnotic drugs exert their antiemetic action primarily via sedation (13). Propofol is a depressant that acts directly on the chemoreceptor trigger zone, vagal nuclei, and other centers implicated in nausea and vomiting (14). However, Borgeat et al. (7) observed that the duration of antiemetic action after the administration of propofol 10 mg in the early postoperative period was much longer than the normal duration of hypnotic action achieved with the 15-fold larger doses of propofol used for induction of anesthesia. Tomioka et al. (15) also observed that propofol at subhypnotic doses was effective in suppressing the severe gagging reaction in dentistry, which is caused by psychogenic factors. The patient described in our report was not sedated while propofol was infused. Therefore, sedation is unlikely to have played an important role in the antiemetic action of propofol.