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Anesth Analg 1999;88:1354
© 1999 International Anesthesia Research Society

GENERAL ARTICLES

Efficacy and Adverse Effects of Prophylactic Antiemetics During Patient-Controlled Analgesia Therapy: A Quantitative Systematic Review

Martin R. Tramèr, MD, DPhil*, and Bernhard Walder, MD{dagger}

Divisions of *Anaesthesiology and {dagger}Anaesthesiological Investigations, Department APSIC, Geneva University Hospital, Geneva, Switzerland

Address correspondence and reprint requests to Martin Tramèr, Division of Anaesthesiology, Department APSIC, Geneva University Hospital, CH-1211 Geneva 14, Switzerland. Address e-mail to martin.tramer{at}hcuge.ch


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Nausea and vomiting are frequent adverse effects of patient-controlled analgesia (PCA) with opioids. To identify the optimal prophylactic antiemetic intervention in this setting, we performed a systematic search for randomized trials (MEDLINE, EMBASE, Cochrane library, reference lists, hand-searching, no language restriction) published up to May 1998 that compared prophylactic antiemetic interventions with placebo or no treatment in the postoperative PCA-setting with opioids. Fourteen placebo-controlled trials (1117 patients) with different regimens of droperidol, ondansetron, hyoscine TTS, tropisetron, metoclopramide, propofol, and promethazine were analyzed. One PCA was with tramadol, all others were with morphine. At 24 h, the cumulative incidence of nausea and vomiting without antiemetics was approximately 50%. Droperidol 0.017–0.17 mg/mg of morphine (0.5–11 mg/d droperidol) was statistically significantly more effective than placebo without evidence of dose-responsiveness; the number needed to treat to prevent nausea compared with placebo was 2.7 (95% confidence interval 1.8–5.2), and that to prevent vomiting was 3.1 (2.3–4.8). Compared with placebo, the incidence of minor adverse effects with droperidol was increased with doses >4 mg/d.

Implications: Of 100 patients treated with droperidol added in a patient-controlled analgesia pump with morphine, 30 who would have vomited or been nauseated had they not received droperidol will not suffer these effects. There is no evidence of dose-responsiveness for efficacy with droperidol, but the risk of adverse effects is dose-dependent. There is a lack of evidence for other antiemetics.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Patient-controlled analgesia (PCA) is a routine technique of pain treatment (1). Opioids are the mainstay of postoperative analgesia with PCA (2). However, postoperative pain control with opioid PCA is often perceived to be highly emetogenic (3). Although there is no evidence that the risk of nausea and vomiting with PCA is more frequent than that with IM opioids (4), patients may refuse to continue PCA treatment because of these side effects.

The best antiemetic prophylaxis for PCA-related emesis is still not known (5). We systematically searched relevant and valid data on antiemetics that are concomitantly used with postoperative opioid PCA. The aim was to search the strongest evidence for the relative efficacy and harm of interventions that are used prophylactically to reduce the incidence of opioid PCA related nausea and vomiting.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
A systematic search for relevant randomized controlled trials was conducted. The search was performed with MEDLINE (from 1966), EMBASE (from 1980), and Cochrane library (1998, issue I) using the free text keywords "nausea," "vomiting," "emesis," "patient-controlled analgesia," and their combination. We performed the last electronic search on April 3, 1998. Reference lists of retrieved reports, relevant review articles, and meta-analyses (1,2,4,5) were checked. Locally available anesthesia journals were hand-searched. No language restriction was applied. We contacted authors by letter when there was uncertainty about the data (for instance, when efficacy data were reported as scores or number of emesis episodes but not in dichotomous form) and requested information on additional unpublished data.

Relevant reports investigated the prophylactic efficacy of antiemetic interventions compared with placebo or no treatment in patients with acute, postoperative pain treated with a PCA device containing an opioid. The antiemetic intervention had to have been given concomitantly with the PCA-opioid. Only studies in which data on efficacy could be extracted in dichotomous form (i.e., presence or absence of emesis with active treatment and control) were included. Only full publications in peer-reviewed journals were considered. Abstracts, letters, and review articles were excluded. Interventions to treat established postoperative nausea and vomiting were not analyzed.

Each report was read independently by both authors to assess the adequacy of randomization and blinding and the description of withdrawals using a validated three-item, five-point scale (6). Reports that were described as "randomized" were given one point, and a further point if the method of randomization was described and adequate (such as a table of random numbers). Randomization was assumed when it was stated as such in the report. There was a pre hoc agreement that trials without randomization or with an inadequate randomization method (i.e., without concealment of treatment allocation, such as randomization according to patient's date of birth or hospital chart number, alternate allocation, etc.) would be excluded from further analysis. One point was given when the trial was described as double-blinded. When the method of double-blinding was described and adequate (identical ampoules, for instance), a further point was given. Finally, reports that described the number and reasons for withdrawals were given one point. Thus, the maximal score of an included randomized controlled trial was 5, and the minimal score was 1. We compared the allocated scores and resolved differences by discussion. Information on patients, surgical settings, dose and regimen of antiemetics, PCA program and opioid doses, study end points, and drug-related adverse effects were extracted from each included report.

Prevention of emetic events was the main end point for efficacy. The incidence of emetic events with active treatments (i.e., experimental event rate) and with placebo or no treatment (i.e., control event rate) was extracted. A maximum of three different events could be extracted from each trial: nausea, vomiting (including retching), and any emetic event (nausea, vomiting, or nausea and vomiting). Events were treated separately. Data on drug-related adverse effects were extracted when they were reported in dichotomous form. Other end points, such as patient satisfaction, cost, or length of hospital stay, were inconsistently reported and therefore were not analyzed.

As in previous similar meta-analyses, we calculated two effect sizes: relative risk and number needed to treat (7,8). Relative risk (i.e., experimental event rate divided by control event rate) was calculated with 95% confidence intervals (9). For combined data, a fixed effect model that considers within-study variation (10) was used when data from no more than two trials were combined or when there was no significant heterogeneity (i.e., P > 0.1). In all other situations, we used a random effects model (11). This statistic incorporates both within- and between-study variance. It yields a more conservative estimate of treatment effect when there is variability of results. A statistically significant difference between active and control conditions was assumed when the 95% confidence interval of the relative risk did not include 1.

The number needed to treat, the reciprocal of the absolute risk reduction, was calculated (12) using data from individual trials and from combined data. A positive number needed to treat indicates how many patients must be treated with a particular antiemetic intervention to find one patient who will not vomit or be nauseated who would have done so had they received the control treatment. Thus, the number needed to treat shows the effort required to achieve a particular therapeutic target (13). A 95% confidence interval around the number needed to treat point estimate was calculated (14).

To estimate the frequency of drug-related adverse effects, we intended to calculate the relative risk and the number needed to harm as for number needed to treat. Adverse events that did not lead to study withdrawal were classified as minor harm. Adverse events that did lead to study withdrawal were classified as major harm.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Twenty-six reports were considered for inclusion. The first was published in 1992, the last in May 1998. We contacted the authors of four reports by letter, and three responded to our inquiry. No relevant unpublished data could be retrieved. Twelve reports were subsequently excluded: eight had no placebo or no treatment control (15–22), one did not report dichotomous efficacy data (23). In one trial, a continuous infusion of morphine rather than a PCA-device, was used (24). In one trial, antiemetic treatment was started 2 h after surgery, when most patients were already symptomatic (25). One report was on treatment of established nausea and vomiting with acupuncture (26).

Fourteen randomized controlled trials including data from 1117 patients met our inclusion criteria (27–40) (Table 1). All trials were in adults. Spinal anesthesia was used in one trial (38), general anesthesia was used in all others. In one trial, PCA was with tramadol (35), and all others were with morphine. The median trial size was 58 (range 30–286). The median quality score was 3 (range 1–4). In most trials, the observation period was >24 h (minimum 18 h , maximum 3 days ).


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  		Table 1. Antiemetics and Patient-Controlled Analgesia-Related Nausea and Vomiting: Analyzed Randomized Controlled Trials with Placebo or No Treatment Controls
 
In the 13 placebo-controlled trials that used PCA with morphine, boluses were 1–2 mg (in one, it was 20 µg/kg) (30), and lockouts ranged from 3–12 min. In four trials, a maximal dose of morphine was set (usually 30 mg per 4 h) (27,28,36,40). In one trial, a background infusion (1 mg/h morphine) was used (31). In the trials that reported the amount of morphine consumption, the average dose of morphine per observation period was between approximately 40 and 90 mg.

Without antiemetic drugs (i.e., opioid PCA plus placebo or no treatment), the incidence of nausea was, on average, 43% (range 22%–80%), of vomiting was 55% (45%–71%), and of any emetic event was 67% (54%–87%). Hyoscine TTS, ondansetron, tropisetron, metoclopramide, propofol, and promethazine were documented in one or two trials with only limited numbers of patients (Table 2).


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  		Table 2. Efficacy of Prophylactic Antiemetic Interventions with Morphine Patient-Controlled Analgesia
 
The most documented antiemetic was droperidol; it was added to morphine PCA in six placebo-controlled trials (27,31–34,38) with data on 642 patients (Table 1). Droperidol was added to tramadol in a further trial (35); these data were not included in the droperidol-morphine analyses.

Relevant droperidol efficacy data for morphine PCA were available from four trials with a 24-h observation period and from one trial each with a 20-h (38) and a 36-h period (33). A wide range of different droperidol regimens was used (Table 1).

Evidence of dose-responsiveness was tested to evaluate the propriety of pooling data. This was done using the number needed to treat as the effect size (7,8). To take account of variations in morphine consumption across trials, we tested evidence for dose-responsiveness with droperidol in placebo-controlled trials fourfold (Fig. 1). First, for each trial, the cumulative droperidol dose per reported observation period was plotted against the respective number needed to treat to prevent nausea and vomiting (Fig. 1A); cumulative droperidol doses per observation period were 1–9 mg (average 5 mg). Second, for each trial, the cumulative droperidol dose was extrapolated to a 24-h observation period (assuming a constant morphine and droperidol consumption between the 20th and 36th postoperative hour) and plotted against the respective number needed to treat to prevent nausea and vomiting (Fig. 1B); doses of droperidol ranged from 1 to 10.6 mg (average 5 mg). Third, for each trial, the droperidol dose per milligram dose of PCA-morphine was plotted against the respective number needed to treat to prevent nausea and vomiting (Fig. 1C); droperidol doses varied between 0.017 and 0.17 mg (average 0.07 mg) per milligram of morphine. Finally, we plotted the dose of droperidol per PCA-bolus against the respective number needed to treat to prevent nausea and vomiting for each trial (Fig. 1D); droperidol doses varied between 0.017 mg and 0.33 mg (average 0.09 mg) per bolus.



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  		Figure 1. Number needed to treat (NNT) to prevent morphine–patient-controlled analgesia related nausea and vomiting with droperidol compared with placebo or no treatment. Each symbol represents one outcome of one trial. All data of trials with multiple active arms (32,34) are shown. {square} = nausea, {diamond} = vomiting, {circ} = any emetic event (nausea and/or vomiting).

 
There was no graphic evidence of any dose-responsiveness (Fig. 1A-D). Most outcomes were between numbers needed to treat two and five. One trial produced an outlier for nausea (27). In this trial, the risk of nausea in control patients was 20% only; the number needed to treat point estimate to prevent nausea with droperidol compared with placebo was 30. In the same trial, the risk of vomiting or any emetic event in controls was 56% and 66%, respectively; the number needed to treat to prevent vomiting or any emetic event with droperidol compared with placebo was approximately three.

Because there was no evidence of dose-responsiveness with the doses of droperidol tested in these trials, we combined efficacy data (Table 2). Droperidol data of multiple arm trials (32,34) were pooled. Compared with placebo or no treatment, the number needed to treat to prevent nausea with any droperidol regimen was 5.1 (95% confidence interval 3.1–15). When the trial with the nausea outlier was excluded (27), the number needed to treat to prevent nausea was 2.7 (1.8–5.2). The number needed to treat to prevent vomiting was 3.1 (2.3–4.8), and the number needed to treat to prevent any emetic event was 2.8 (2.1–3.9).

Data on adverse reactions with droperidol came from two sources. First, relevant data were reported in four placebo-controlled droperidol trials (27,31,33,34). Second, six randomized studies without a placebo or no treatment group that were not included in efficacy analyses reported dichotomous data on adverse reactions with droperidol (15,17,18,20,21,38). One compared droperidol with cyclizine (20), one compared different droperidol regimens (15), and four compared a small, single-bolus dose of droperidol (0.5–2.5 mg) given to all randomized patients (i.e., all patients—control patients included—received droperidol) (17,18,21,38). To increase power and to estimate drug-related risk over a wider range of doses, we included these incidence data from active-controlled trials in the analysis. We took incidence data (i.e., absolute risks) on minor harm of all treatment arms of all 10 droperidol trials (i.e., placebo- and active-controlled) and plotted them against droperidol dose and placebo, respectively (Fig. 2). Thus, incidence data on adverse events from placebo patients, control patients receiving a single bolus of droperidol, and patients treated with droperidol added to PCA-morphine were plotted on the same graph. There was no intention to analyze these data quantitatively.



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  		Figure 2. Absolute risk (incidence) of minor adverse-drug reactions (i.e. not leading to study withdrawal) with placebo, single boluses of droperidol, and cumulative doses of droperidol added to morphine patient-controlled analgesia. Data are from single treatment arms. Squares = drowsiness, sedation, dizziness; diamonds = anxiety, restlessness, agitation.

 
With placebo, the absolute risk of minor adverse events (sedation, drowsiness and dizziness or anxiety, restlessness and agitation) was 0%–20% (Fig. 2). In those trials that reported adverse drug reactions, droperidol doses ranged from 1.2 mg (bolus of 0.02 mg/kg ) to cumulative doses of 7.4 mg (21) (Fig. 2). There was no obvious difference in the incidence of minor adverse effects compared with placebo with droperidol doses <=4 mg. With increasing doses of droperidol, the absolute risk increased. Data on minor adverse events from one report were excluded from this graph because all patients received hyoscine as premedication, plus an initial bolus of droperidol 0.5 mg before the start of the PCA treatment (17). In this trial, the incidence of restlessness, dizziness, or anxiety was extraordinary high: 57% in control patients and 63% with droperidol added to PCA-morphine.

In all droperidol trials (placebo- and active-controlled), 539 patients received any dose of droperidol. Two trials reported adverse effect-related study withdrawal (i.e., major harm) (31,38). In one, a patient who received droperidol felt excessively drowsy; the average droperidol dose in this trial was 8.8 mg/20 h (38). In the other trial, a patient receiving droperidol became lethargic; the average droperidol dose in this trial was 2.8 mg/d (31). No extrapyramidal symptoms were described in any trial.

The two trials that investigated the antiemetic effect of hyoscine reported minor adverse drug reactions (30,39). Both reported a 90% incidence of dry mouth with hyoscine TTS, compared with a 45% and 90% incidence, respectively, with sham TTS. In 107 treated patients, the number needed to harm for a dry mouth with hyoscine TTS compared with not using it was 4.4 (95% confidence interval 2.7–11), relative risk 1.3 (1.09–1.55). Both trials also reported blurred vision; the incidence with active and control was 5% and 0% (30) and 38% and 30% (39). When these data were pooled, the difference between active and control was not statistically significant; the relative risk was 1.36 (0.69–2.69) and the number needed to harm point estimate was 12. The other antiemetic interventions were too poorly tested to allow firm conclusions.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
In these systematically searched trials, the incidence of nausea and vomiting in patients not receiving any antiemetic treatment added to their PCA-morphine was approximately 50%. This high control event rate most likely reflects a high underlying risk and justifies trials that investigate the efficacy of prophylactic antiemetic interventions to reduce PCA-related nausea and vomiting. Indeed, the opioid PCA setting may be regarded as a clinical model to investigate the efficacy of antiemetic interventions on opioid-induced nausea and vomiting.

The large variability in the control event rate for postoperative nausea and vomiting is well know (41). It may be due to variations in the study populations (different surgeries, different patients, etc.), but it may also simply be due to random chance in these relatively small trials (42).

Droperidol was the most frequently reported antiemetic; >370 patients received the drug prophylactically in six placebo-controlled trials. Thus, recommendations can be based on evidence. Six different regimens were tested in six trials. This most likely reflects uncertainty about which droperidol regimen is the most effective and the least harmful. Graphical display did not suggest any relationship between dose and efficacy (Fig. 1). This means that within a wide range of doses (a factor of 10 between the minimal and the maximal dose), droperidol added to morphine PCA has a constant degree of antiemetic efficacy: one in three patients who would have vomited or been nauseated had they received a placebo will not suffer these effects. We do not know whether this is the best result that can be achieved; however, these data suggest that giving a small dose of an antiemetic at the same time as the emetogenic stimulus (i.e., mixing droperidol with morphine) may be the most successful and sensible approach to reducing morphine PCA related nausea and vomiting.

Knowing that droperidol is effective when mixed with morphine PCA, the main questions concern the likelihood of harm of this intervention and whether adverse drug reactions are dose-dependent. Contrary to droperidol's efficacy data, there was evidence for dose-responsiveness when analyzing data on drug-related minor harm. When patients receive >4–6 mg/d droperidol, minor adverse events are likely to occur more often than they would without the drug. Adverse effect-related study withdrawal (i.e., major harm) was rare, but it did happen. In 2 of 539 patients (0.4%) receiving any dose of droperidol, PCA treatment had to be stopped because of excessive drowsiness; in one trial, the cumulative 24-h dose of droperidol was as low as 2.8 mg (31). We do not know whether excessive drowsiness in these patients was caused by the droperidol, the morphine, or a combination. Extrapyramidal reactions were not reported. We may be 95% confident that, in adults, extrapyramidal reactions with droperidol added to morphine PCA will not occur more frequently than 3 in 539 (56 in 10,000 patients) (43).

The second most frequently reported drugs were 5-HT3 receptor antagonists (ondansetron, tropisetron). Their effect on vomiting seemed to be satisfactory with numbers needed to treat of approximately five compared with placebo, but there was no evidence of any antinausea effect (Table 2). Some of the other interventions showed promising results (clonidine, promethazine) but were based on very limited numbers of patients; recommendations cannot be based on the available evidence. The current data do not allow consideration of hyoscine, propofol, and metoclopramide as worthwhile antiemetic treatments in the morphine PCA setting.

A number of trials were designed as placebo-controlled trials (i.e., in the control group, saline was added to morphine PCA), but a closer look revealed that all patients had actually received a dose (albeit small) of the antiemetic. Thus, these trials could not be regarded as truly placebo-controlled (or "no treatment"). These data therefore were of no use in estimating the antiemetics' relative efficacy. Placebo controls may have been omitted for ethical reasons. This, however, is contentious. Contrary to widespread opinion, trials without placebo controls are not likely to further our understanding of the efficacy of antiemetic interventions in the postoperative setting (44).

A pooled effect size estimated by meta-analysis should be considered provisional. Thus, the results of this systematic review must be confirmed. Eight different prophylactic antiemetic interventions were tested in these trials. Droperidol was the best documented drug, and its antiemetic efficacy (one in three patients will benefit) is clinically relevant. It may therefore be argued that we should first obtain more insight into droperidol's prophylactic efficacy in the morphine PCA setting before spending research resources to test alternative interventions. For instance, there was a lack of dose-responsiveness with droperidol. Its optimal dose, the minimal effective dose without untoward adverse effects, for preventing morphine PCA related nausea and vomiting is unknown. In this systematic review, taking droperidol's efficacy and harm data together, it is very likely that Figure 1 shows the upper horizontal plateau of the sigmoid dose-response curve, rather than the lower plateau. Thus, ultrasmall doses of droperidol added to morphine PCA should be tested. We need large, randomized, placebo-controlled trials comparing different doses of droperidol to establish its optimal dose for morphine PCA related nausea and vomiting. In a small, prospective, dose-finding study, the optimal dose of droperidol in adults seemed to be 0.1 mg/mg of morphine (15). Based on this systematic review, however, the optimal dose is likely to be <0.1 mg of droperidol per milligram of morphine (Fig. 1C) or <4 mg/d droperidol (Fig. 1A).


   Acknowledgments
 
This work was supported by a PROSPER research grant from the Swiss National Science Foundation (Grant No 3233–051939.97).

We thank Daniel Haake from the Documentation Service of the Swiss Academy of Medical Sciences for his invaluable help in searching electronic databases.


   References
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 Methods
 Results
 Discussion
 References
 

  1. Lehmann KA. Update of patient-controlled analgesia. Anaesthesiol 1997;10:374–9.
  2. Peacock J, Dale S. Patient-controlled analgesia. Curr Opin Anaesthesiol 1996;9:313–7.
  3. Tuckey J, Marjot R. PCE: patient-controlled emesis [letter]. Anaesthesia 1995;50:180.
  4. Ballantyne JC, Carr DB, Chalmers TC, et al. Postoperative patient-controlled analgesia: meta-analyses of initial randomized control trials. J Clin Anesth 1993;5:182–93.[ISI][Medline]
  5. Woodhouse A, Mather LE. Nausea and vomiting in the postoperative patient-controlled analgesia environment. Anaesthesia 1997;52:770–5.[ISI][Medline]
  6. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1–12.[ISI][Medline]
  7. Tramèr MR, Moore RA, Reynolds DJ, et al. A quantitative systematic review of ondansetron in treatment of established postoperative nausea and vomiting. BMJ 1997;314:1088–92.[Abstract/Free Full Text]
  8. Tramèr MR, Reynolds DJM, Moore RA, et al. Efficacy, dose-response, and safety of ondansetron in prevention of postoperative nausea and vomiting: a quantitative systematic review of randomised placebo-controlled trials. Anesthesiology 1997;87:1277–89.[ISI][Medline]
  9. Morris JA, Gardner MJ. Calculating confidence intervals for relative risk, odds ratios, and statistical guidelines. In: Gardner MJ, Altman DG, eds. Statistics with confidence: confidence intervals and statistical guidelines. London:BMJ, 1995:50–63.
  10. Yusuf S, Peto R, Lewis J, et al. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Res 1985;27:335–71.
  11. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–88.[ISI][Medline]
  12. Laupacis A, Sackett DL, Roberts RS. An assessment of clinically useful measures of the consequences of treatment. N Engl J Med 1988;318:1728–33.[ISI][Medline]
  13. McQuay HJ, Moore RA. Using numerical results from systematic reviews in clinical practice. Ann Intern Med 1997;126:712–20.[Abstract/Free Full Text]
  14. Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect. BMJ 1995;310:452–4.[Free Full Text]
  15. Lamond CT, Robinson DL, Boyd JD, et al. Addition of droperidol to morphine administered by the patient-controlled analgesia method: what is the optimal dose? Eur J Anaesthesiol 1998;15:304–9.[ISI][Medline]
  16. McKenzie R, Tantisira B, Jackson D, et al. Antiemetic efficacy of a droperidol-morphine combination in patient-controlled analgesia. J Clin Anesth 1995;7:141–7.[ISI][Medline]
  17. Roberts CJ, Millar JM, Goat VA. The antiemetic effectiveness of droperidol during morphine patient-controlled analgesia. Anaesthesia 1995;50:559–62.[ISI][Medline]
  18. Sharma SK, Davies MW. Patient-controlled analgesia with a mixture of morphine and droperidol. Br J Anaesth 1993;71:435–6.[Abstract/Free Full Text]
  19. Walder AD, Aitkenhead AR. Antiemetic efficacy of metoclopramide when included in a patient-controlled analgesia infusion. Anaesthesia 1994;49:804–6.[ISI][Medline]
  20. Walder AD, Aitkenhead AR. A comparison of droperidol and cyclizine in the prevention of postoperative nausea and vomiting associated with patient-controlled analgesia. Anaesthesia 1995;50:654–6.[ISI][Medline]
  21. Williams OA, Clarke FL, Harris RW, et al. Addition of droperidol to patient-controlled analgesia: effect on nausea and vomiting. Anaesthesia 1993;48:881–4.[ISI][Medline]
  22. Wrench IJ, Ward JEH, Walder AD, et al. The prevention of postoperative nausea and vomiting using a combination of ondansetron and droperidol. Anaesthesia 1996;51:776–8.[ISI][Medline]
  23. Barrow PM, Hughes DG, Redfern N, et al. Influence of droperidol on nausea and vomiting during patient-controlled analgesia. Br J Anaesth 1994;72:460–1.[Abstract/Free Full Text]
  24. Grebenik CR, Allman C. Nausea and vomiting after cardiac surgery. Br J Anaesth 1996;77:356–9.[Abstract/Free Full Text]
  25. Harris SN, Sevarino FB, Sinatra RS, et al. Nausea prophylaxis using transdermal scopolamine in the setting of patient-controlled analgesia. Obstet Gynecol 1991;78:673–7.[Abstract/Free Full Text]
  26. McConaghy P, Bland D, Swales H. Acupuncture in the management of postoperative nausea and vomiting in patients receiving morphine via a patient-controlled analgesia system. Acupunct Med 1996;14:2–5.
  27. Alexander R, Lovell AT, Seingry D, et al. Comparison of ondansetron and droperidol in reducing postoperative nausea and vomiting associated with patient-controlled analgesia. Anaesthesia 1995;50:1086–8.[ISI][Medline]
  28. Bree SE, West MJ, Taylor PA, et al. Combining propofol with morphine in patient-controlled analgesia to prevent postoperative nausea and vomiting. Br J Anaesth 1998;80:152–4.[Abstract/Free Full Text]
  29. Davies PRF, Warwick P, O'Connor M. Antiemetic efficacy of ondansetron with patient-controlled analgesia. Anaesthesia 1996;51:880–2.[ISI][Medline]
  30. Doyle E, Byers G, McNicol LR, et al. Prevention of postoperative nausea and vomiting with transdermal hyoscine in children using patient-controlled analgesia. Br J Anaesth 1994;72:72–6.[Abstract/Free Full Text]
  31. Freedman GM, Kreitzer JM, Reuben SS, et al. Improving patient-controlled analgesia: adding droperidol to morphine sulfate to reduce nausea and vomiting and potentiate analgesia. Mt Sinai J Med 1995;62:221–5.[Medline]
  32. Gan TJ, Alexander R, Fennelly M, et al. Comparison of different methods of administering droperidol in patient-controlled analgesia in the prevention of postoperative nausea and vomiting. Anesth Analg 1995;80:81–5.[Abstract]
  33. Kaufmann MA, Rosow C, Schnieper P, et al. Prophylactic antiemetic therapy with patient-controlled analgesia: a double-blind, placebo-controlled comparison of droperidol, metoclopramide, and tropisetron. Anesth Analg 1994;78:988–94.[Abstract/Free Full Text]
  34. Klahsen AJ, O'Reilly D, McBride J, et al. Reduction of post-operative nausea and vomiting with the combination of morphine and droperidol in patient-controlled analgesia. Can J Anaesth 1996;43:1100–7.[Abstract/Free Full Text]
  35. Ng KFJ, Tsui SL, Yang JCS, et al. Comparison of tramadol and tramadol/droperidol mixture for patient-controlled analgesia. Can J Anaesth 1997;44:810–5.[Abstract/Free Full Text]
  36. Ozalp G, Kuru N, Guner F, Kadiogullari N. Prophylactic antiemetic therapy with patient-controlled analgesia: ondansetron and tropisetron. Turk Anesteziyol Reanim 1997;25:173–6.
  37. Park J, Forrest J, Kolesar R, et al. Oral clonidine reduces postoperative PCA morphine requirements. Can J Anaesth 1996;43:900–6.[Abstract/Free Full Text]
  38. Russell D, Duncan LA, Frame WT, et al. Patient-controlled analgesia with morphine and droperidol following caesarean section under spinal anaesthesia. Acta Anaesthesiol Scand 1996;40:600–5.[ISI][Medline]
  39. Semple P, Madej TH, Wheatley RG, et al. Transdermal hyoscine with patient-controlled analgesia. Anaesthesia 1992;47:399–401.[ISI][Medline]
  40. Silverman DG, Freilich J, Sevarino FB, et al. Influence of promethazine on symptom-therapy scores for nausea during patient-controlled analgesia with morphine. Anesth Analg 1992;74:735–8.[Abstract/Free Full Text]
  41. Tramèr M, Moore A, McQuay H. Prevention of vomiting after paediatric strabismus surgery: a systematic review using the numbers-needed-to-treat method. Br J Anaesth 1995;75:556–61.[Abstract/Free Full Text]
  42. Moore RA, Gavaghan D, Tramèr MR, et al. Size is everything: large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects. Pain. In press.
  43. Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA 1983;249:1743–5.[ISI][Medline]
  44. Tramèr MR, Reynolds DJM, Moore RA, et al. When placebo controlled trials are essential and equivalence trials are inadequate. BMJ 1998;317:875–80.[Free Full Text]
Accepted for publication October 6, 1998.




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