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Combining propofol with morphine in patient-controlled analgesia to prevent postoperative nausea and vomiting
British Journal of Anaesthesia 1998; 80: 152–154
Combining propofol with morphine in patient-controlled analgesia to prevent postoperative nausea and vomiting S. E. BREE, M. J. WEST, P. A. TAYLOR AND I. G. KESTIN
Summary We have studied the antiemetic effects of propofol when mixed with morphine in a patientcontrolled analgesia (PCA) pump after major gynaecological surgery. In a double-blind, randomized, controlled study, 50 women, ASA I or II, received a standardized anaesthetic comprising thiopental, morphine, atracurium, nitrous oxide and oxygen with enflurane, and received postoperative PCA with morphine mixed with either 1% propofol or Ivelip. The PCA bolus was morphine 1 mg with propofol 5 mg or Ivelip 0.5 ml, with a lockout time of 5 min. Postoperative nausea and vomiting (PONV) were assessed by the nursing staff using a four-point ordinal scale and by the patient using a visual analogue scale for 48 h after surgery. The two groups were similar in the potential factors influencing the incidence of PONV. There were no significant differences between the two groups in any of the study measurements of PONV. There were no side effects after propofol. Propofol, when mixed with morphine in this dose combination for PCA, did not decrease the incidence of nausea and vomiting in women undergoing major gynaecological surgery. (Br. J. Anaesth. 1998; 80: 152–154) Keywords: anaesthetics i.v., propofol; analgesics opioid, morphine; vomiting, nausea; vomiting, postoperative; analgesia, patient-controlled
Postoperative nausea and vomiting (PONV) is one of the more common and distressing causes of morbidity after major surgery. There is a decreased incidence of PONV after propofol.1–4 Whether propofol has direct antiemetic properties or is merely less emetogenic than other anaesthetic drugs is not known. There has been interest in using subhypnotic doses of propofol both to treat and prevent nausea and vomiting after cancer chemotherapy and surgery.5–8 Small doses of propofol given in recovery were successful in treating PONV,7 but the results with postoperative infusion for 24–48 h after surgery were conflicting.8–11 We have studied the effects of simultaneous administration of propofol and morphine patient-controlled analgesia (PCA) on the incidence of PONV.
Patients and methods After obtaining approval from the local Ethics Committee, we studied ASA I or II women, aged 30–75
yr, undergoing elective hysterectomy (either abdominal or vaginal). We excluded women weighing more than 100 kg, those who were unable to use patient-controlled analgesia (PCA) and any patient who suffered from epilepsy, ear disease, liver disease, hyperlipidaemia or were receiving drugs with antiemetic properties. After obtaining written informed consent, all patients were premedicated with temazepam 20–30 mg, 1 h before surgery. Anaesthesia was induced with thiopental, atracurium and morphine 0.2 mg kg91, and maintained with enflurane (end-tidal 0.5–2%) and 60% nitrous oxide in oxygen. At the end of surgery residual neuromuscular block was antagonized with neostigmine 2.5 mg and glycopyrrolate 0.5 mg. After extubation of the trachea all patients were transferred to the recovery area where they received a PCA (Graseby 3300) consisting of morphine 100 mg mixed in 50 ml of either 1% propofol or 10% Ivelip (10% soya oil, 2.5% glycerol, Clintec). Derriford Hospital Pharmacy prepared all the study solutions under aseptic conditions and randomized the patients. The stability of morphine, propofol and Ivelip mixtures have been verified previously by HPLC (Dr P. Adams, principal pharmacist, South West Pharmaceutical Quality Control Laboratory, Torbay Hospital, Torquay, personal communication). The patient, anaesthetist, investigators and all nurses were unaware of the contents of the syringe. Another two syringes, each containing 1 ml of either propofol or 10% Ivelip, were supplied by the pharmacy with the appropriate PCA syringe. The first 1-ml bolus was given i.v. by the recovery nurse if the patient complained of nausea or was vomiting. The second syringe was given 5 min later, followed by rescue antiemetic (prochlorperazine 12.5 mg i.m. every 6 h) after another 5 min, as required. The PCA pump was programmed to give morphine 1 mg with either propofol 5 mg or Ivelip 0.5 ml in each successful demand, with a lockout of 5 min. The maximum possible dose of propofol in 1 h was 60 mg. A separate i.v. cannula was used for the PCA. All patients were prescribed oxygen for 24 h and when comfortable were transferred to the ward. S. E. BREE†, FRCA, M. J. WEST‡, FRCA, P. A. TAYLOR, FRCA, I. G. KESTIN*, FRCA, Department of Anaesthesia, Derriford Hospital, Derriford Road, Plymouth PL6 8DH. Accepted for publication: September 27, 1997. *Address for correspondence: Department of Anaesthesia, Western Infirmary, Dumbarton Road, Glasgow G11 6NT. Present addresses: †Department of Anaesthesia, Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH. ‡Department of Anaesthesia, Harefield Hospital, Hillend Road, Harefield, Middlesex UB9 6JH.
Morphine with propofol PCA for prevention of PONV Table 1 Patient characteristics and recovery times (number (%), or mean (SD) [range])
153 System B-7.01), and the level of statistical significance was 5%.
Propofol (n:25) Ivelip (n:24) Age (yr) 45 [30–75] Weight (kg) 70 (12.6) Body mass index 26 [17–33] History of motion sickness 3 (12%) History of PONV 9 (36%) Duration of anaesthesia (min) 100 (23.5) Time in recovery (min) 69 (33.5)
46 [33–67] 68 (14.2) 25 [18–32] 1 (4%) 5 (20%) 96 (20.3) 70 (28.8)
Table 2 Analgesia and sedation in the two groups (mean (95% confidence intervals) or median [range]) Time Morphine (mg)
0–24 h 24–48 h Pain VAS 0–24 h 24–48 h Sedation 0–24 h 24–48 h Propofol (mg h91) 0–24 h 24–48 h
Propofol
Ivelip
47 (36–58) 40 (30–50) 12 (4–20) 5 (2–9) 3.3 [0–8.0] 3.4 [0–9.2] 2.2 [0–8.5] 1.0 [0–8.3] 2.0 [1.3–3.8] 2.0 [1.3–4.3] 1.3 [1.0–2.0] 1.0 [1.0–3.0] 9.8 (7.5–12.1) 2.6 (0.9–4.2)
Table 3 Incidence of PONV and use of antimetics in the two groups (number (%) or median [range])
Nausea
Propofol (n:25)
Ivelip (n:24)
17 3
16 2
(68%) (12%)
(67%) (8%)
1.3 [1–2.3] 1 [1–2]
1.2 [1–1.8] 1 [1–1.7]
2.4 [0–10] 0 [0–9.1] 3 (12%) 3 (12%) 0
2.0 [0–10] 0 [0–6.4] 4 (16%) 2 (8%) 2 (8%)
15 3
(60%) (12%)
16 2
(67%) (8%)
At 4-hourly intervals for the first 24 h, and 8-hourly intervals for the second 24 h, the ward nurses recorded PCA demands and doses, nausea scores, episodes of vomiting, antiemetics given and sedation scores. PONV was recorded as: (1) no nausea or vomiting; (2) nausea alone; (3) nausea with vomiting on one or two occasions; and (4) nausea with vomiting more than twice. Sedation was recorded as: (1) awake; (2) dozing intermittently; (3) mostly sleeping; and (4) only awakens when aroused. Mean nausea scores for each patient were obtained as the mean of the nursing PONV scores during each 24-h period. In addition, at 24 and 48 h, patients completed two 10-cm visual analogue scales (VAS) for pain and nausea, ranging from none to the worst possible. The amount of morphine and rescue antiemetics given by the nurses were also recorded. The sample size was chosen to provide a 75% probability of demonstrating a reduction in the incidence of PONV from 60% to 30% when ␣:0.05. The data were analysed using the Student’s t test, Mann–Whitney U test and Fisher’s exact test, where appropriate (Instat v2.01, GraphPad; Macintosh
Results A total of 50 patients were entered into the study. One patient receiving Ivelip was excluded within the first 24 h because of excessive sedation; 25 patients received propofol and 24 received Ivelip. Patient characteristics, duration of anaesthesia and time spent in recovery were similar in both groups (table 1). The amount of morphine used from the PCA, visual analogue scores for pain and sedation scores were similar in both groups at 24 and 48 h (table 2). There were no significant differences between the two groups in any of the measurements of PONV (table 3).
Discussion Postoperative nausea and vomiting (PONV) after anaesthesia is less likely with propofol than with other anaesthetic agents, and the magnitude of the reduction depends on the method of administration, time of measurement and baseline incidence of PONV.4 PONV is least when propofol is used for maintenance and induction of anaesthesia.4 The action of propofol on dopamine12–14 and 5HT3 receptors15 has been investigated, and it seems unlikely that propofol has important activity at these receptors. There has been interest in using propofol specifically as an antiemetic drug, both as treatment and for prophylaxis.1 Propofol 10 mg given in recovery was effective in 69% of patients with established PONV (compared with 35% responding to placebo).7 Schulman, Rockett and Canada reported that a patient with severe refractory PONV was treated successfully with a propofol infusion for 5 days.16 Gan and colleagues have published their preliminary results using a target-controlled infusion of propofol to treat PONV in recovery.17 Patients with PONV were given infusions of propofol in increasing doses until treatment was successful or the study limit (a target concentration of 800 ng ml91) was reached. They found that a target concentration of 405 ng ml91 reduced the verbal nausea score to less than 3 or by 50%. This blood concentration of propofol would normally be obtained with a bolus dose of 10 mg and an infusion of 1 mg kg91 h91. Details of the patients, anaesthetic techniques and whether a control group were used were not given.17 Postoperative infusions of propofol have been tried as prophylaxis against PONV, with conflicting results.8–11 Patients in the study by Ewalenko and colleagues8 received an infusion of propofol started in recovery after thyroid surgery. The incidence of PONV was reduced from 65% (in the control group) to 10%,8 but patients in two other studies did not benefit from using propofol in this way.9 10 In these three studies,8–10 propofol was not used for anaesthesia, although Scudieri and colleagues10 started the subhypnotic infusion of propofol before anaesthesia and surgery. Modest success has been reported in
154 reducing the severity of PONV after intrathecal morphine using a postoperative infusion of propofol for 24 h.11 Our premise when starting this study was that by coupling the dose of propofol to that of morphine and by using boluses, which have been shown to be effective, propofol with morphine in a PCA may be an effective technique for both analgesia and antiemesis. In addition, continuous infusion of propofol requires an additional i.v. cannula and syringe driver, and we found this a practical disadvantage in our previous study.9 The maximum dose of propofol that could be obtained from the PCA pump was 60 mg in 1 h; in practice, the mean propofol dose was much less than this, and the maximum dose of propofol received during any 4-h period by a patient in this study was 180 mg. This is considerably less than would be delivered using the 1-mg kg91 h91 scheme of previous studies of continuous postoperative infusions of propofol.9 10 The dose of propofol obtained by the patients from the PCA in our study may have been too low if propofol does indeed have antiemetic properties. We chose a propofol bolus dose of 5 mg, which we thought would be safe for the patients to receive on the ward. If we had used a 10-mg bolus, and morphine consumption remained the same, the mean hourly propofol dose would have been 19.6 mg in the first 24 h. This is still less than 1 mg kg91 h91 used previously for prophylaxis of nausea and vomiting after surgery9 10 or cancer chemotherapy.5 6 However, the patient who used the most propofol in any 4-h period in this study would have received a mean of 90 mg per hour if a 10-mg propofol bolus had been chosen. She weighed 68 kg, so the dose would have been more than 1 mg kg91 h91 during this time; this may not be safe on a general ward. In summary, we believe that it is unlikely that propofol will have important postoperative use in treating or avoiding PONV.
Acknowledgement We thank the staff of Derriford Hospital Pharmacy for their help.
References 1. Borgeat A, Wilder-Smith OHG, Suter PM. The nonhypnotic therapeutic applications of propofol. Anesthesiology 1994; 80: 642–656.
British Journal of Anaesthesia 2. McCollum JSC, Milligan KR, Dundee JW. The anti emetic action of propofol. Anaesthesia 1988; 43: 239–240. 3. Gunawardene RD, White DC. Propofol and emesis. Anaesthesia 1988; 43 (Suppl.): 65–67. 4. Tramer M, Moore A, McQuay H. Propofol anaesthesia and postoperative nausea and vomiting: quantitative systematic review of randomised controlled studies. British Journal of Anaesthesia 1997; 78: 247–255. 5. Borgeat A, Wilder-Smith OHG, Wilder-Smith CH, Forni M, Suter PM. Propofol improves patient comfort during cisplatin chemotherapy. A pilot study. Oncology 1993; 50: 456–459. 6. Scher CS, Amar D, McDowall RH, Barst SM. Use of propofol for the prevention of chemotherapy-induced nausea and emesis in oncology patients. Canadian Journal of Anaesthesia 1992; 39: 170–172. 7. Borgeat A, Wilder-Smith OHG, Saiah M, Rifat K. Subhypnotic doses of propofol possess direct anti emetic properties. Anesthesia and Analgesia 1992; 74: 539–541. 8. Ewalenko P, Janny S, Dejonckheere M, Andry G, Wyns C. Antiemetic effect of subhypnotic doses of propofol after thyroidectomy. British Journal of Anaesthesia 1996; 77: 463–467. 9. Montgomery JE, Sutherland CJ, Kestin IG, Sneyd JR. Infusions of subhypnotic doses of propofol for the prevention of post operative nausea and vomiting. Anaesthesia 1996; 51: 554–557. 10. Scuderi PE, D’Angelo R, Harris L, Mims GR, Weeks DB, James RL. Small dose propofol by continuous infusion does not prevent postoperative vomiting in females undergoing outpatient laparoscopy. Anesthesia and Analgesia 1997; 84: 71–75. 11. Torn K, Tuominen M, Tarkkila P, Lindgren L. Effects of subhypnotic doses of propofol on the side effects of intrathecal morphine. British Journal of Anaesthesia 1994; 73: 411–412. 12. Appadu BL, Strange PG, Lambert DG. Does propofol interact with D2 receptors? Anesthesia and Analgesia 1994; 79: 1191–1192. 13. Hvarfner A, Hammas B, Thorn SE, Wattwil M. The influence of propofol on vomiting induced by apomorphine. Anesthesia and Analgesia 1995; 80: 967–969. 14. Borgeat A. Subhypnotic doses of propofol do not possess antidopaminergic properties. Anesthesiology 1997; 84: 196– 198. 15. Machu TK, Harris RA. Alcohols and anaesthetics enhance the function of 5-hydroxytryptamine receptors expressed in Xenopus laevis oocytes. Journal of Pharmacology and Experimental Therapeutics 1994; 271: 898–905. 16. Schulman SR, Rockett CB, Canada AT. Long-term propofol infusion for refractory postoperative nausea: a case report with quantitative propofol analysis. Anesthesia and Analgesia 1995; 80: 636–637. 17. Gan TJ, Glass PSA, Ginsberg B, Canada A, Grant AP, Goodman D. Determination of the plasma concentration of propofol to treat postoperative nausea and vomiting. Anesthesiology 1996; 85: A332.
Combining propofol with morphine in patient-controlled analgesia to prevent postoperative nausea and vomiting S. E. BREE, M. J. WEST, P. A. TAYLOR AND I. G. KESTIN
Summary We have studied the antiemetic effects of propofol when mixed with morphine in a patientcontrolled analgesia (PCA) pump after major gynaecological surgery. In a double-blind, randomized, controlled study, 50 women, ASA I or II, received a standardized anaesthetic comprising thiopental, morphine, atracurium, nitrous oxide and oxygen with enflurane, and received postoperative PCA with morphine mixed with either 1% propofol or Ivelip. The PCA bolus was morphine 1 mg with propofol 5 mg or Ivelip 0.5 ml, with a lockout time of 5 min. Postoperative nausea and vomiting (PONV) were assessed by the nursing staff using a four-point ordinal scale and by the patient using a visual analogue scale for 48 h after surgery. The two groups were similar in the potential factors influencing the incidence of PONV. There were no significant differences between the two groups in any of the study measurements of PONV. There were no side effects after propofol. Propofol, when mixed with morphine in this dose combination for PCA, did not decrease the incidence of nausea and vomiting in women undergoing major gynaecological surgery. (Br. J. Anaesth. 1998; 80: 152–154) Keywords: anaesthetics i.v., propofol; analgesics opioid, morphine; vomiting, nausea; vomiting, postoperative; analgesia, patient-controlled
Postoperative nausea and vomiting (PONV) is one of the more common and distressing causes of morbidity after major surgery. There is a decreased incidence of PONV after propofol.1–4 Whether propofol has direct antiemetic properties or is merely less emetogenic than other anaesthetic drugs is not known. There has been interest in using subhypnotic doses of propofol both to treat and prevent nausea and vomiting after cancer chemotherapy and surgery.5–8 Small doses of propofol given in recovery were successful in treating PONV,7 but the results with postoperative infusion for 24–48 h after surgery were conflicting.8–11 We have studied the effects of simultaneous administration of propofol and morphine patient-controlled analgesia (PCA) on the incidence of PONV.
Patients and methods After obtaining approval from the local Ethics Committee, we studied ASA I or II women, aged 30–75
yr, undergoing elective hysterectomy (either abdominal or vaginal). We excluded women weighing more than 100 kg, those who were unable to use patient-controlled analgesia (PCA) and any patient who suffered from epilepsy, ear disease, liver disease, hyperlipidaemia or were receiving drugs with antiemetic properties. After obtaining written informed consent, all patients were premedicated with temazepam 20–30 mg, 1 h before surgery. Anaesthesia was induced with thiopental, atracurium and morphine 0.2 mg kg91, and maintained with enflurane (end-tidal 0.5–2%) and 60% nitrous oxide in oxygen. At the end of surgery residual neuromuscular block was antagonized with neostigmine 2.5 mg and glycopyrrolate 0.5 mg. After extubation of the trachea all patients were transferred to the recovery area where they received a PCA (Graseby 3300) consisting of morphine 100 mg mixed in 50 ml of either 1% propofol or 10% Ivelip (10% soya oil, 2.5% glycerol, Clintec). Derriford Hospital Pharmacy prepared all the study solutions under aseptic conditions and randomized the patients. The stability of morphine, propofol and Ivelip mixtures have been verified previously by HPLC (Dr P. Adams, principal pharmacist, South West Pharmaceutical Quality Control Laboratory, Torbay Hospital, Torquay, personal communication). The patient, anaesthetist, investigators and all nurses were unaware of the contents of the syringe. Another two syringes, each containing 1 ml of either propofol or 10% Ivelip, were supplied by the pharmacy with the appropriate PCA syringe. The first 1-ml bolus was given i.v. by the recovery nurse if the patient complained of nausea or was vomiting. The second syringe was given 5 min later, followed by rescue antiemetic (prochlorperazine 12.5 mg i.m. every 6 h) after another 5 min, as required. The PCA pump was programmed to give morphine 1 mg with either propofol 5 mg or Ivelip 0.5 ml in each successful demand, with a lockout of 5 min. The maximum possible dose of propofol in 1 h was 60 mg. A separate i.v. cannula was used for the PCA. All patients were prescribed oxygen for 24 h and when comfortable were transferred to the ward. S. E. BREE†, FRCA, M. J. WEST‡, FRCA, P. A. TAYLOR, FRCA, I. G. KESTIN*, FRCA, Department of Anaesthesia, Derriford Hospital, Derriford Road, Plymouth PL6 8DH. Accepted for publication: September 27, 1997. *Address for correspondence: Department of Anaesthesia, Western Infirmary, Dumbarton Road, Glasgow G11 6NT. Present addresses: †Department of Anaesthesia, Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH. ‡Department of Anaesthesia, Harefield Hospital, Hillend Road, Harefield, Middlesex UB9 6JH.
Morphine with propofol PCA for prevention of PONV Table 1 Patient characteristics and recovery times (number (%), or mean (SD) [range])
153 System B-7.01), and the level of statistical significance was 5%.
Propofol (n:25) Ivelip (n:24) Age (yr) 45 [30–75] Weight (kg) 70 (12.6) Body mass index 26 [17–33] History of motion sickness 3 (12%) History of PONV 9 (36%) Duration of anaesthesia (min) 100 (23.5) Time in recovery (min) 69 (33.5)
46 [33–67] 68 (14.2) 25 [18–32] 1 (4%) 5 (20%) 96 (20.3) 70 (28.8)
Table 2 Analgesia and sedation in the two groups (mean (95% confidence intervals) or median [range]) Time Morphine (mg)
0–24 h 24–48 h Pain VAS 0–24 h 24–48 h Sedation 0–24 h 24–48 h Propofol (mg h91) 0–24 h 24–48 h
Propofol
Ivelip
47 (36–58) 40 (30–50) 12 (4–20) 5 (2–9) 3.3 [0–8.0] 3.4 [0–9.2] 2.2 [0–8.5] 1.0 [0–8.3] 2.0 [1.3–3.8] 2.0 [1.3–4.3] 1.3 [1.0–2.0] 1.0 [1.0–3.0] 9.8 (7.5–12.1) 2.6 (0.9–4.2)
Table 3 Incidence of PONV and use of antimetics in the two groups (number (%) or median [range])
Nausea
Propofol (n:25)
Ivelip (n:24)
17 3
16 2
(68%) (12%)
(67%) (8%)
1.3 [1–2.3] 1 [1–2]
1.2 [1–1.8] 1 [1–1.7]
2.4 [0–10] 0 [0–9.1] 3 (12%) 3 (12%) 0
2.0 [0–10] 0 [0–6.4] 4 (16%) 2 (8%) 2 (8%)
15 3
(60%) (12%)
16 2
(67%) (8%)
At 4-hourly intervals for the first 24 h, and 8-hourly intervals for the second 24 h, the ward nurses recorded PCA demands and doses, nausea scores, episodes of vomiting, antiemetics given and sedation scores. PONV was recorded as: (1) no nausea or vomiting; (2) nausea alone; (3) nausea with vomiting on one or two occasions; and (4) nausea with vomiting more than twice. Sedation was recorded as: (1) awake; (2) dozing intermittently; (3) mostly sleeping; and (4) only awakens when aroused. Mean nausea scores for each patient were obtained as the mean of the nursing PONV scores during each 24-h period. In addition, at 24 and 48 h, patients completed two 10-cm visual analogue scales (VAS) for pain and nausea, ranging from none to the worst possible. The amount of morphine and rescue antiemetics given by the nurses were also recorded. The sample size was chosen to provide a 75% probability of demonstrating a reduction in the incidence of PONV from 60% to 30% when ␣:0.05. The data were analysed using the Student’s t test, Mann–Whitney U test and Fisher’s exact test, where appropriate (Instat v2.01, GraphPad; Macintosh
Results A total of 50 patients were entered into the study. One patient receiving Ivelip was excluded within the first 24 h because of excessive sedation; 25 patients received propofol and 24 received Ivelip. Patient characteristics, duration of anaesthesia and time spent in recovery were similar in both groups (table 1). The amount of morphine used from the PCA, visual analogue scores for pain and sedation scores were similar in both groups at 24 and 48 h (table 2). There were no significant differences between the two groups in any of the measurements of PONV (table 3).
Discussion Postoperative nausea and vomiting (PONV) after anaesthesia is less likely with propofol than with other anaesthetic agents, and the magnitude of the reduction depends on the method of administration, time of measurement and baseline incidence of PONV.4 PONV is least when propofol is used for maintenance and induction of anaesthesia.4 The action of propofol on dopamine12–14 and 5HT3 receptors15 has been investigated, and it seems unlikely that propofol has important activity at these receptors. There has been interest in using propofol specifically as an antiemetic drug, both as treatment and for prophylaxis.1 Propofol 10 mg given in recovery was effective in 69% of patients with established PONV (compared with 35% responding to placebo).7 Schulman, Rockett and Canada reported that a patient with severe refractory PONV was treated successfully with a propofol infusion for 5 days.16 Gan and colleagues have published their preliminary results using a target-controlled infusion of propofol to treat PONV in recovery.17 Patients with PONV were given infusions of propofol in increasing doses until treatment was successful or the study limit (a target concentration of 800 ng ml91) was reached. They found that a target concentration of 405 ng ml91 reduced the verbal nausea score to less than 3 or by 50%. This blood concentration of propofol would normally be obtained with a bolus dose of 10 mg and an infusion of 1 mg kg91 h91. Details of the patients, anaesthetic techniques and whether a control group were used were not given.17 Postoperative infusions of propofol have been tried as prophylaxis against PONV, with conflicting results.8–11 Patients in the study by Ewalenko and colleagues8 received an infusion of propofol started in recovery after thyroid surgery. The incidence of PONV was reduced from 65% (in the control group) to 10%,8 but patients in two other studies did not benefit from using propofol in this way.9 10 In these three studies,8–10 propofol was not used for anaesthesia, although Scudieri and colleagues10 started the subhypnotic infusion of propofol before anaesthesia and surgery. Modest success has been reported in
154 reducing the severity of PONV after intrathecal morphine using a postoperative infusion of propofol for 24 h.11 Our premise when starting this study was that by coupling the dose of propofol to that of morphine and by using boluses, which have been shown to be effective, propofol with morphine in a PCA may be an effective technique for both analgesia and antiemesis. In addition, continuous infusion of propofol requires an additional i.v. cannula and syringe driver, and we found this a practical disadvantage in our previous study.9 The maximum dose of propofol that could be obtained from the PCA pump was 60 mg in 1 h; in practice, the mean propofol dose was much less than this, and the maximum dose of propofol received during any 4-h period by a patient in this study was 180 mg. This is considerably less than would be delivered using the 1-mg kg91 h91 scheme of previous studies of continuous postoperative infusions of propofol.9 10 The dose of propofol obtained by the patients from the PCA in our study may have been too low if propofol does indeed have antiemetic properties. We chose a propofol bolus dose of 5 mg, which we thought would be safe for the patients to receive on the ward. If we had used a 10-mg bolus, and morphine consumption remained the same, the mean hourly propofol dose would have been 19.6 mg in the first 24 h. This is still less than 1 mg kg91 h91 used previously for prophylaxis of nausea and vomiting after surgery9 10 or cancer chemotherapy.5 6 However, the patient who used the most propofol in any 4-h period in this study would have received a mean of 90 mg per hour if a 10-mg propofol bolus had been chosen. She weighed 68 kg, so the dose would have been more than 1 mg kg91 h91 during this time; this may not be safe on a general ward. In summary, we believe that it is unlikely that propofol will have important postoperative use in treating or avoiding PONV.
Acknowledgement We thank the staff of Derriford Hospital Pharmacy for their help.
References 1. Borgeat A, Wilder-Smith OHG, Suter PM. The nonhypnotic therapeutic applications of propofol. Anesthesiology 1994; 80: 642–656.
British Journal of Anaesthesia 2. McCollum JSC, Milligan KR, Dundee JW. The anti emetic action of propofol. Anaesthesia 1988; 43: 239–240. 3. Gunawardene RD, White DC. Propofol and emesis. Anaesthesia 1988; 43 (Suppl.): 65–67. 4. Tramer M, Moore A, McQuay H. Propofol anaesthesia and postoperative nausea and vomiting: quantitative systematic review of randomised controlled studies. British Journal of Anaesthesia 1997; 78: 247–255. 5. Borgeat A, Wilder-Smith OHG, Wilder-Smith CH, Forni M, Suter PM. Propofol improves patient comfort during cisplatin chemotherapy. A pilot study. Oncology 1993; 50: 456–459. 6. Scher CS, Amar D, McDowall RH, Barst SM. Use of propofol for the prevention of chemotherapy-induced nausea and emesis in oncology patients. Canadian Journal of Anaesthesia 1992; 39: 170–172. 7. Borgeat A, Wilder-Smith OHG, Saiah M, Rifat K. Subhypnotic doses of propofol possess direct anti emetic properties. Anesthesia and Analgesia 1992; 74: 539–541. 8. Ewalenko P, Janny S, Dejonckheere M, Andry G, Wyns C. Antiemetic effect of subhypnotic doses of propofol after thyroidectomy. British Journal of Anaesthesia 1996; 77: 463–467. 9. Montgomery JE, Sutherland CJ, Kestin IG, Sneyd JR. Infusions of subhypnotic doses of propofol for the prevention of post operative nausea and vomiting. Anaesthesia 1996; 51: 554–557. 10. Scuderi PE, D’Angelo R, Harris L, Mims GR, Weeks DB, James RL. Small dose propofol by continuous infusion does not prevent postoperative vomiting in females undergoing outpatient laparoscopy. Anesthesia and Analgesia 1997; 84: 71–75. 11. Torn K, Tuominen M, Tarkkila P, Lindgren L. Effects of subhypnotic doses of propofol on the side effects of intrathecal morphine. British Journal of Anaesthesia 1994; 73: 411–412. 12. Appadu BL, Strange PG, Lambert DG. Does propofol interact with D2 receptors? Anesthesia and Analgesia 1994; 79: 1191–1192. 13. Hvarfner A, Hammas B, Thorn SE, Wattwil M. The influence of propofol on vomiting induced by apomorphine. Anesthesia and Analgesia 1995; 80: 967–969. 14. Borgeat A. Subhypnotic doses of propofol do not possess antidopaminergic properties. Anesthesiology 1997; 84: 196– 198. 15. Machu TK, Harris RA. Alcohols and anaesthetics enhance the function of 5-hydroxytryptamine receptors expressed in Xenopus laevis oocytes. Journal of Pharmacology and Experimental Therapeutics 1994; 271: 898–905. 16. Schulman SR, Rockett CB, Canada AT. Long-term propofol infusion for refractory postoperative nausea: a case report with quantitative propofol analysis. Anesthesia and Analgesia 1995; 80: 636–637. 17. Gan TJ, Glass PSA, Ginsberg B, Canada A, Grant AP, Goodman D. Determination of the plasma concentration of propofol to treat postoperative nausea and vomiting. Anesthesiology 1996; 85: A332.