1Department of Anaesthesiology, Soonchunhyang University Hospital, 657 Hannam-Dong, Yongsan-Ku, Seoul, Korea. 2Department of Anaesthesiology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, 50 Ilwon-Dong, Kangnam-Ku, Seoul, Korea. 3Department of Anaesthesiology, Hallym University Hospital, 445 Gil-Dong, Kangdong-Ku, Seoul, Korea*Corresponding author
Accepted for publication: June 29, 2000
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Abstract |
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Br J Anaesth 2000; 85: 898900
Keywords: vomiting, nausea, postoperative; vomiting, antiemetics; anaesthetics i.v., propofol; analgesia, patient-controlled; analgesics opioid, fentanyl
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Introduction |
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The direct and indirect antiemetic effects of propofol are well known. As an anaesthetic, propofol has been associated with a lower incidence of PONV.1 Propofol infusion in subhypnotic doses has been used successfully to manage chemotherapy-induced emesis.2 Its efficacy for the prevention of PONV, however, has not been proven conclusively.3,4
This prospective, randomized, double-blind, placebo-controlled study was undertaken to investigate whether continuous subhypnotic propofol infusion would prevent PONV in female patients receiving fentanyl i.v. PCA and to determine the optimal infusion rates of propofol.
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Methods and results |
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Patients who had significant systemic diseases, those who had vomited or received antiemetics within 24 h before surgery, and those with known allergy to propofol or a history of epilepsy were not included. Also excluded were those with high risk factors such as a previous history of PONV or migraine, or women who were menstruating.
On the day before surgery, patients and their care-givers were instructed in the use of an APII PCA pump (Baxter Healthcare Co., Deerfield, IL, USA) and in the use of the nausea/vomiting and sedation score card. They were told to ask for rescue antiemetics when PONV occurred. One hour before surgery, midazolam 35 mg and glycopyrrolate 0.2 mg were given intramuscularly. Anaesthesia was induced with thiopental 5 mg kg1 i.v. and fentanyl 23 µg kg1, and maintained with enflurane, 50% nitrous oxide and oxygen. All received vecuronium 0.1 mg kg1 to facilitate tracheal intubation and for subsequent intra-operative neuromuscular blockade. At the end of surgery, this was reversed with pyridostigmine 10 mg and glycopyrrolate 0.2 mg i.v.
Medication was blinded and randomized by our pharmacy, which delivered covered and coded vials of propofol or Intralipid. After patients had regained consciousness in the recovery room, a bolus of Intralipid 1 ml or propofol (Pofol; Je-Il Pharmaceutical Co., Seoul, Korea) 10 mg was given intravenously followed by continuous infusion of intralipid as a placebo or propofol using an infusion pump. Those given propofol boluses were randomly allocated to receive one of four infusion regimens for 24 h: continuous propofol infusion at 5, 10, 15 or 20 µg kg1 min1.
All patients received fentanyl i.v. as postoperative analgesia via another PCA pump. The fentanyl concentration was 20 µg ml1, total volume 100 ml and bolus dose 20 µg; there was no basal infusion. The lockout interval was 6 min.
Droperidol 1.25 mg i.v. was to be administered promptly as a rescue antiemetic when requested. Patients and their care-givers were given score cards and asked to record the occurrence of nausea and vomiting. The investigator, blinded to the study drugs, verified the PONV episodes 4, 8 and 24 h after surgery and recorded sedation scores and other adverse side effects. Total fentanyl consumption during the first 24 h after surgery was recorded at the end of the study period. Pain scores were not measured in this investigation.
PONV was assessed on a three-point scale: 0=no symptoms, 1=only nausea, 2=vomiting. The highest score reported during the study determined the category to which a patient was allocated. Thus, patients who experienced both nausea and vomiting were included in the vomiting category. Sedation was evaluated on a five-point scale: 0=awake, 1=drowsy, 2=asleep but responds to verbal commands, 3=asleep but responds to physical stimulus, 4=unrousable.
Statistical analysis was performed with SPSS version 7.5 (SPSS Inc., Chicago, IL, USA). Discontinuous data were analysed using the chi-square test, and continuous data by one-way analysis of variance with Bonferroni correction for multiple comparisons between the study groups. A P-value of <0.05 was considered significant.
The results are presented in Table 1. All groups were comparable with regard to patient characteristics and type and duration of surgical procedures. Patients in the placebo group used significantly less fentanyl than those who received propofol 20 µg kg1 min1 (P<0.05). Sixty-five per cent of the patients who received propofol 15 µg kg1 min1 and 70% of those who received propofol 20 µg kg1 min1 experienced no nausea or vomiting, compared with 25% of those who received placebo (P<0.05). Power analysis indicated that the sample size used here, 20 patients in each group, would be adequate to detect a 40% decrease in PONV with 90% power and an error of 0.05.
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Discussion |
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Studies investigating the use of continuous subhypnotic propofol infusion for the prevention of PONV have produced conflicting results. Ewalenko and colleagues reported that subhypnotic propofol infusion at 1 mg kg1 h1 effectively reduced the incidence of PONV from 65% to 10% without untoward sedative or cardiovascular effects after thyroidectomy.3 Montgomery and colleagues4 used a similar propofol infusion regimen but were unable to demonstrate any specific antiemetic effect over placebo. Our study showed that propofol infusion significantly reduced the incidence of PONV from 75% to 30%, similar to the results of Ewalenko and colleagues.3
There might be a therapeutic range of propofol concentration that prevents PONV. It has been shown that propofol for anaesthesia is associated with less PONV than volatile agents, but that it reduced only early PONV.1 In previous studies on the management of chemotherapy-induced emesis and prophylaxis of PONV, 1 mg kg1 min1 (17 µg kg1 min1) has been used as the continuous subhypnotic dose of propofol infusion.2 Recently, Gan and colleagues demonstrated that a plasma concentration of propofol at 343 ng ml1 was associated with 50% reduction in postoperative nausea.6 Simulations indicated that a bolus dose of 10 mg followed by an infusion at approximately 10 µg kg1 min1 are necessary to achieve this plasma concentration. Based on these reports, propofol infusion rates of 520 µg kg1 min1 were selected for this study.
In our study, the patients who received propofol 20 µg kg1 min1 were more sedated than those receiving placebo 4 h after surgery, even though none developed respiratory depression. This might have been related to residual sedative effects of inhalational anaesthetics and the concurrent use of fentanyl by PCA. Thus, continuous infusion of high dose propofol combined with opioids such as fentanyl should be carried out cautiously.
Fentanyl consumption in the placebo group was significantly less than that in the propofol 20 µg kg1 min1 group. We feel that this was mainly because patients resisted pressing the button on the PCA pump, being afraid of aggravating PONV induced by PCA use.
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Acknowledgements |
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References |
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