Anesth Analg 1999;89:798
© 1999 International Anesthesia Research Society
CASE REPORTS
Propofol Is Effective in Chemotherapy-Induced Nausea and Vomiting: A Case Report with Quantitative Analysis
Shigemasa Tomioka, DDS, PhD,
Tomiko Kurio, DDS,
Kazumi Takaishi, DDS, and
Nobuyoshi Nakajo, DDS, PhD
Department of Dental Anesthesiology, Tokushima University, School of Dentistry, Tokushima, Japan
Address correspondence and reprint requests to Shigemasa Tomioka, DDS, PhD, Department of Dental Anesthesiology, Tokushima University, School of Dentistry, 3 Kuramoto-cho, Tokushima City, Tokushima 770-8504, Japan.
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Introduction
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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.
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Case Report
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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.
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Discussion
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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.
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References
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Gralla RJ, Itri LM, Pisko SE, et al. Antiemetic efficacy of high-dose metoclopramide randomized trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting. N Engl J Med 1981;305:905–9.[Abstract]
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Marty M, Pouillart P, Scholl S, et al. Comparison of the 5-hydroxytryptamine 3 (serotonin) antagonist ondansetron (GR 38032F) with high-dose metoclopramide in the control of cisplatin- induced emesis. Engl J Med 1990;322:816–21.[Abstract]
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Scher CS, Amar D, McDowall RH, Barst SM. Use of propofol for the prevention of chemotherapy-induced nausea and emesis in oncology patients. Can J Anaesth 1992;39:170–2.[Abstract/Free Full Text]
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Borgeat A, Wilder-Smith OHG, Wilder-Smith CH, et al. Propofol improves patient comfort during cisplatin chemotherapy. Oncology 1993;50:456–9.[ISI][Medline]
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Borgeat A, Wilder-Smith O, Forni M, Suter PM. Adjuvant propofol enables better control of nausea and emesis secondary to chemotherapy for breast cancer. Can J Anaesth 1994;41:1117–9.[Abstract/Free Full Text]
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Gepts E, Camu F, Cockshott ID, Douglas EJ. Disposition of propofol administered as constant rate intravenous infusions in humans. Anesth Analg 1987;66:1256–63.[Abstract/Free Full Text]
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Borgeat A, Wilder-Smith OHG, Saiah M, Rifat K. Subhypnotic doses of propofol possess direct antiemetic properties. Anesth Analg 1992;74:539–41.[Abstract/Free Full Text]
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Schulman SR, Rockett CB, Canada AT, Glass PSA. Long-term propofol infusion for refractory postoperative nausea a case report with quantitative propofol analysis. Anesth Analg 1995;80:636–7.[ISI][Medline]
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Cubeddu LX, Hoffmann IS, Fuenmayor NT, Finn AL. Efficacy of ondansetron (GR 38032F) and the role of serotonin in cisplatin- induced nausea and vomiting. N Engl J Med 1990;322:810–6.[Abstract]
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Wilder-Smith OHG, Borgeat A, Chappuis P, et al. Urinary serotonin metabolite excretion during cisplatin chemotherapy. Cancer 1993;72:2239–41.[ISI][Medline]
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Appadu BL, Lambert DG. Interaction of i.v. anaesthetic agents with 5-HT3 receptors. Anaesth 1996;76:271–3.
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Borgeat A. Subhypnotic doses of propofol do not possess antidopaminergic properties. Anesth Analg 1997;84:196–8.[Abstract]
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Moyer JH. Effective antiemetic agents. Med Clin North Am 1957;41:405–32.
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Appadu BL, Strange PG, Lambert DG. Does propofol interact with D2 dopamine receptor? Anesth Analg 1994;79:1191–2.[Free Full Text]
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Tomioka S, Uchida D, Eguchi S, Nakajo N. Elimination of hypersensitive gagging reaction to dentistry by propofol at subhypnotic doses. Oral Dis 1998;4:279–80.[Medline]
Accepted for publication May 21, 1999.
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Introduction
Case Report
