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PAIN MEDICINE

The Antiemetic Efficacy of Droperidol Added to Morphine Patient-Controlled Analgesia: A Randomized, Controlled, Multicenter Dose-Finding Study

Xavier Culebras, MD^*, Jean-Baptiste Corpataux, MD, Giovanni Gaggero, MD, and Martin R. Tramèr, MD DPhil^*

*Division d’Anesthésie, Département APSIC (Anesthéie, Pharmacologie et Soins Intensif de Chirurgie), Hôpitaux Universitaires de Genève, Genève, Switzerland; Service d’Anesthésie, Hôpital de La Chaux-de-Fonds, La Chaux-de-Fonds, Switzerland; and Service d’Anesthésie, Hôpital Sud Fribourgeois, Riaz, Switzerland

Address correspondence and reprint requests to X. Culebras, MD, Division of Anaesthesiology, Rue Micheli du Crest 24, Geneva University Hospitals, CH-1211 Geneva 14, Switzerland. Address e-mail to xavier.culebras{at}hcuge.ch

	Abstract

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The antiemetic dose response of droperidol when it is added to patient-controlled analgesia with morphine is not well known. We randomly allocated adults who received postoperative morphine patient-controlled analgesia (1-mg bolus, 5-min lockout) to one of four regimens: no droperidol (control) or 5, 15, or 50 µg of droperidol per milligram of morphine. Efficacy and adverse effects were recorded during 24 h and were analyzed with number needed to treat (NNT) and number needed to harm with 95% confidence intervals. Data from 82 controls, 82 patients receiving droperidol 5 µg, 82 receiving droperidol 15 µg, and 83 receiving droperidol 50 µg were analyzed. Average consumption of droperidol per 24 h was 0.2 mg with the 5-µg regimen, 0.61 mg with the 15-µg regimen, and 2.04 mg with the 50-µg regimen. In controls, the incidence of nausea was 48.8%; with droperidol 5 µg, it was 42.7% (NNT compared with control, 16 [95% confidence interval, 4.7 to -11]); with 15 µg, it was 32.9% (NNT, 6.3 [3.3–100]); and with 50 µg, it was 21.7% (NNT, 3.7 [2.4 to 7.6]). In controls, the incidence of vomiting was 24.4%; with droperidol 5 µg, it was 23.2% (NNT compared with control, 82 [7 to -8.5]); with 15 µg, it was 22.0% (NNT, 41 [6.5 to -9.6]); and with 50 µg, it was 12% (NNT, 8.1 [4.2–142]). In controls, the incidence of pruritus was 12.2%; with droperidol 5 µg, it was 6.1% (NNT compared with control, 16 [6.7 to -37]); and with 15 and 50 µg, it was 2.4% (NNT, 10 [5.7–52]). In controls, the incidence of sedation was 2.4%; with droperidol 5 µg, it was 8.5% (number needed to harm (NNH) compared with control, 16 [7.7 to -123]); with 15 µg, it was 6.1% (NNH, 27 [10 to -40]); and with 50 µg, it was 18.1% (NNH, 6.4 [4.1–15]). There were no extrapyramidal symptoms and no cardiac adverse events. There was no difference in patient satisfaction. The optimal antiemetic dose of droperidol is 15–50 µg/mg of morphine. Larger doses may have more antivomiting efficacy but are likely to be unacceptably sedating.

IMPLICATIONS: In a patient-controlled analgesia (PCA) pump, droperidol 5 µg/mg of morphine is not antiemetic, antipruritic, or sedative. Droperidol 15 µg shows some antiemetic efficacy, is antipruritic, and is not sedative. Droperidol 50 µg is clearly antiemetic, is no more antipruritic than 15 µg, and is clearly sedative. In a PCA pump with morphine, the optimal dose of droperidol is 15–50 µg/mg of morphine.

	Introduction

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Patient-controlled analgesia (PCA) with morphine has become an integral part of postoperative pain control. However, one of the limiting factors of analgesia with morphine is nausea and vomiting (1). To reduce the incidence of this unpleasant adverse drug reaction, numerous antiemetic interventions that are given concomitantly with opioid PCA have been tested. A systematic review that compared the relative efficacy of antiemetic interventions in this setting reported on three main results (2). First, the only antiemetic that was examined in several randomized trials and that showed consistent antiemetic efficacy when added to morphine in a PCA pump was the butyrophenone droperidol. Second, there was a lack of evidence of dose responsiveness for antiemetic efficacy with droperidol; doses as small as 17 µg/mg of morphine (i.e., 1.7 mg of droperidol per 100 mg of morphine) seemed to be as effective as 170 µg (i.e., 17 mg of droperidol per 100 mg of morphine). Third, droperidol-related minor adverse effects (drowsiness, sedation, and restlessness) increased in a dose-dependent fashion. The authors concluded that the optimal dose of droperidol was less than 10 mg/100 mg of morphine, mainly because of an increased risk of adverse drug reactions with larger doses (2). A randomized study provided further important information on the role of droperidol in a PCA pump with morphine (3). This trial was conducted in female patients undergoing gynecological surgeries and compared 4 droperidol regimens that were added to morphine PCA: 50, 100, 150, and 200 µg of droperidol per milligram of morphine. Again, there was no clear evidence of dose responsiveness despite a large range of doses studied. In that trial, the incidence of nausea was approximately 30% with all 4 regimens; the incidence of vomiting was between 0% and 20% and was independent of the dose. However, with all four doses, half of the patients were drowsy or asleep. The authors concluded that droperidol 100 µg/mg of morphine (i.e., 10 mg of droperidol per 100 mg of morphine) was the optimal dose in this setting (3). The aim of this prospective, randomized, observer-blinded, multicenter study was to identify the dose responsiveness of the antiemetic efficacy and of the harm of droperidol when it is added to morphine PCA. On the basis of data from all relevant randomized, controlled trials (2), our prior hypothesis was that to find a dose response, doses less than 5 mg of droperidol per 100 mg of morphine needed to be tested.

	Methods

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This study was approved by the institutional research advisory board and the ethics committee. Written, informed consent was obtained from all patients. Elective surgical patients, ASA physical status I–III, aged 18–80 yr, scheduled for postoperative analgesia with a PCA device with morphine were included. Patients who received neuroleptic therapy or spinal opioids, those with an extrapyramidal syndrome, those with a history of allergy or adverse reaction to butyrophenones, and those with renal insufficiency or an inability to understand the requirements of the protocol were not included. Before surgery, the PCA device (Abbott, North Chicago, IL) was explained to the patients. The anesthesiologist who was in charge of the patient had free choice of drugs used for premedication and for anesthesia and was not further involved in postoperative patient care or data collection. Preoperative or intraoperative antiemetics were not allowed. A standard PCA program was used throughout the study period: morphine solution 100 mg/100 mL of physiological saline; morphine bolus 1 mL (i.e., 1 mg); lockout 5 min; and maximal dose of morphine during 4 h, 40 mg, with no background infusion.

According to a computer-generated random sequence, patients were allocated to one of four groups. Randomization was performed in three separate blocks (according to the three participating centers). Treatment allocation was kept concealed in numbered, opaque envelopes; these were opened consecutively and only after the patients had entered the study. Patients of the first group did not receive any droperidol (controls). A placebo group was not feasible because at the time of setting up the trial, our hospital pharmacy was unable to ensure the chemical stability of preprepared morphine-droperidol mixtures over several weeks. Patients of the second group received droperidol 5 µg/mg of morphine (0.5 mg added to 100 mg of morphine). Patients of the third group received droperidol 15 µg/mg of morphine (1.5 mg added to 100 mg of morphine). Patients of the fourth group received droperidol 50 µg/mg of morphine (5 mg added to 100 mg of morphine).

In the recovery room, PCA bags with morphine, physiological saline, and droperidol were prepared according to treatment allocation by nurses who were not further involved in observation or data collection. Morphine was titrated by using the prepared morphine-droperidol solution; 1-mL boluses were given every 5 min until the patients rated their pain <3 on a 0 (no pain) to 10 (worst imaginable pain) numerical verbal scale. This was performed by an anesthesiologist or an anesthesia nurse who was unaware of treatment allocation. The bag was then placed into the PCA device, and the patient was encouraged to activate the PCA pump when analgesia was deemed necessary.

Data recording up to 24 h after the start of the PCA was performed by one of three investigators, who were unaware of treatment allocation. The primary end-point was the absence of nausea and vomiting (including retching); incidences of nausea and retching or vomiting were separately recorded and analyzed. Secondary end-points were patient satisfaction and adverse effects (respiratory depression, sedation, pruritus, and extrapyramidal symptoms). At the end of the study period, patients were asked to rate their global satisfaction concerning the PCA treatment on a 0–100 visual analog scale (VAS) (0 = not at all satisfied to 100 = very much satisfied). If they felt unsatisfied (arbitrarily defined as VAS_satisfaction <50), they were asked why. Respiratory depression was defined as a respiratory rate <8 breaths/min; according to the study protocol, PCA was stopped in these patients, and naloxone 40 µg was given IV if deemed necessary. Sedation was estimated in the recovery room and on the ward by using a five-point scale as previously described (0 = awake and alert; 1 = drowsy and oriented; 2 = drowsy and disoriented; 3 = asleep but rousable; 4 = asleep and unrousable) (3). A sedation score 2 was regarded as unacceptable in this context. Patients were asked if they felt bothered by any itching. Patients were also observed for any symptoms of akinesia, dyskinesia, agitation, restlessness, or fear. During the stay in the recovery room, patients were continuously monitored with a three-lead electrocardiogram, digital pulse oximetry, and noninvasive blood pressure. Finally, total morphine consumption, including the initial titration dose, was recorded after 24 h. Antiemetic rescue treatment (IV ondansetron) was available at any time.

To ensure the sensitivity of our assay, we analyzed data only from patients who had consumed at least 5 mg of morphine. Data from patients who dropped out of the study because of adverse events were taken into account until withdrawal. All droperidol regimens were separately compared with the no-treatment control. Dichotomous data were analyzed with the inverse of the absolute risk difference, the number needed to treat (NNT) for efficacy, and the number needed to harm (NNH) for adverse events with 95% confidence interval (CI) (4). The NNT/NNH indicated how many patients have to be treated with a given droperidol regimen for one to show a particular end-point (efficacy or harm) who would not have shown this end-point had they all received PCA morphine without droperidol (i.e., control). The 95% CI around the NNT/NNH includes only positive or only negative values if the difference between droperidol and control is statistically significant (i.e., P < 0.05). Accordingly, for a nonsignificant result, the 95% CI around the NNT/NNH expands from a positive value to a negative value (i.e., from a reduction to an increase in the risk difference) (5). To compare means or medians, we used the unpaired Student’s t-test. A two-tailed P value <0.05 was considered statistically significant.

We tested for dose responsiveness by using three a priori definitions. First, if one dose of droperidol was not different from control and if larger doses consistently were, we regarded this as evidence of dose responsiveness. Second, as in previous analyses for antiemetic efficacy, we considered a decrease in the NNT by >20% when increasing the dose as a clinically relevant improvement (6). This would justify the use of the larger dose. Third, the optimal dose of droperidol was the dose with which we regarded the adverse-effect profile to be acceptable and with which any further increase in the dose would not lead to a worthwhile improvement in the antiemetic efficacy (i.e., a decrease in the NNT by >20%).

On the basis of the results of a previously published metaanalysis (2), we expected an incidence of nausea and vomiting without antiemetic prophylaxis of approximately 50% and with an effective dose of droperidol of approximately 20%. Thus, we needed 40 patients per group to show a statistically significant difference between droperidol and control ( = 0.05; ß = 0.2). We doubled that number to study with more confidence the dose responsiveness and adverse-effect profile of droperidol, and we added five patients per group to allow for dropouts.

	Results

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We randomized 340 patients (85 per group). After exclusion of 11 patients, we eventually analyzed data from 329 (Geneva, n = 214; La Chaux-de-Fonds, n = 75; La Riaz, n = 40) (Fig. 1). There were 82 patients in the control group, 82 received droperidol 5 µg/mg of morphine, 82 received droperidol 15 µg/mg of morphine, and 83 received droperidol 50 µg/mg of morphine. There were no statistically significant differences in demographic data among groups (Table 1). The average morphine consumption per 24 h was between 39.5 mg (with droperidol 5 µg) and 49.3 mg (in controls) (P > 0.05). The maximum morphine consumption per 24 h was 130 mg in a control patient. The average droperidol dose per 24 h was 0.2 mg in the droperidol 5 µg group, was 0.62 mg in the droperidol 15 µg group, and was 2.04 mg in the droperidol 50 µg group (Table 1). The maximum dose of droperidol per 24 h was 5.4 mg in a patient of the droperidol 50 µg group.

View larger version (13K): [in this window] [in a new window]   Figure 1. Flowchart. PCA = patient-controlled analgesia; IT = intrathecal.

View larger version (31K): [in this window] [in a new window]   Figure 2. Antiemetic efficacy of three droperidol patient-controlled analgesia regimens (5, 15, and 50 µg/mg of morphine) compared with no treatment (control). Horizontal bars are 95% confidence intervals.

With control, the cumulative incidence of any emetic event (i.e., nausea, retching, vomiting) after 24 h was 52.4%; with droperidol 5 µg, it was 46.3%; with 15 µg, it was 34.1%; and with 50 µg, it was 25.3%. The smallest dose was not statistically significantly different from control; the NNT was 16 (95% CI, 4.7 to -11). With increasing doses, the differences became statistically significant, and the NNTs decreased; with 15 µg, the NNT compared with control was 5.5 (95% CI, 3–30), and with 50 µg it was 3.7 (95% CI, 2.4 to 7.8) (Fig. 2).

With control, the incidence of pruritus was 12.2%; with droperidol 5 µg, it was 6.1%; and with 15 or 50 µg, it was 2.4%. The smallest dose was not statistically significantly different from control; the NNT was 16 (95% CI, 6.7 to -37). With both 15 and 50 µg, the difference was statistically significant, and the NNT was 10 (95% CI, 5.7–52) (Fig. 3).

View larger version (15K): [in this window] [in a new window]   Figure 3. Pruritus with three droperidol patient-controlled analgesia regimens (5, 15, and 50 µg/mg of morphine) compared with no treatment (control). Horizontal bars are 95% confidence intervals.

View larger version (16K): [in this window] [in a new window]   Figure 4. Sedation (score 2 = drowsy and disoriented or 3 = asleep but rousable) with three droperidol PCA regimens (5, 15, and 50 µg/mg of morphine) compared with no treatment (control). Horizontal bars are 95% confidence intervals.

With control, the median VAS_satisfaction was 80 (range, 20–100); with droperidol 5 µg, it was 80 (range, 0–100); with 15 µg, it was 80 (range, 40–100); and with 50 µg, it was 80 (range, 40–100) (P > 0.05). Fifteen patients (4.6%) were unsatisfied (VAS_satisfaction <50) because of nausea and vomiting: these included 7 controls, 4 patients with droperidol 5 µg, and 2 each with droperidol 15 and 50 µg (P > 0.05). Seven patients (2.1%) were unsatisfied because they felt somnolent or sedated: 1 each with control and droperidol 5 µg and 5 with droperidol 50 µg (P > 0.05). Twenty patients (6.1%) were unsatisfied because of insufficient pain relief: these included 2 controls, 7 patients with droperidol 5 µg, 4 patients with 15 µg, and 7 patients with 50 µg (P > 0.05).

	Discussion

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This randomized trial produced five main results. First, there was a dose response for the antiemetic efficacy of droperidol when it was added to morphine PCA. The smallest dose tested, 5 µg, did not show any worthwhile antiemetic efficacy. The medium dose, 15 µg, was effective against nausea but not against vomiting. The largest dose, 50 µg, was effective against both nausea and vomiting. When the dose was increased from 15 to 50 µg, the NNT for the antinausea effect decreased (i.e., the efficacy increased) by >40%. According to our a priori definition, this is a worthwhile increase in efficacy. Previous studies were unable to show this dose response because they did not test similar dose ranges (2,3). Second, droperidol’s antinausea effect was more pronounced compared with its antivomiting effect. Of 100 patients treated with the 50-µg droperidol regimen, approximately 27 will not have nausea within 24 hours of use of the morphine PCA, but only half as many (12 patients) will not vomit who would have done so had they all received a morphine PCA without droperidol. We do not know whether this weaker antivomiting effect was related to the decreased risk of vomiting in our study; only approximately 25% of the controls who did not receive any droperidol vomited, but almost 50% of the controls felt nauseated. These data on a different effect of droperidol on nausea and vomiting, however, are in agreement with the results of a previously published systematic review that evaluated the efficacy of droperidol as a prophylaxis for postoperative nausea and vomiting (7). Thus, droperidol seems to have a stronger antinausea effect and a weaker antivomiting effect for both postoperative nausea and vomiting and for sickness related to morphine PCA. Third, droperidol was antipruritic. Again, the smallest dose tested, 5 µg, did not show efficacy. With 15 and 50 µg, approximately 10 of 100 treated patients will not be bothered by itching who would have been had they received the morphine alone. The beneficial effect of droperidol on opioid-induced pruritus has been described previously (8); the biological basis for this effect remains unclear. Fourth, droperidol was sedative in a dose-dependent manner. With the 2 smaller doses, 5 and 15 µg, there was no significant increase in the number of patients who felt drowsy or were asleep. With the largest doses tested, however, sedation was obvious; of 100 patients receiving 50 µg of droperidol per milligram of morphine, 16 will have a sedation score of 2 or 3 on a 4-point scale. These patients will feel drowsy or disoriented or will be asleep (although rousable). According to our a priori definition, this degree of sedation was unacceptable. Finally, among the 255 patients who were randomized to receive one of the droperidol regimens, there were no observations of extrapyramidal symptoms or cardiac arrhythmia. Although we did not actively search for cardiac abnormalities (for instance, QT prolongation), it is unlikely that we missed a torsade de pointe arrhythmia. However, if there were no serious neurological or cardiac adverse events among 255 patients, we may be 95% confident that with these droperidol regimens, extrapyramidal symptoms or cardiac arrhythmia will not occur more often than in 0.012% (9).

This study was designed to establish dose responsiveness for the antiemetic efficacy of droperidol in a morphine PCA pump. We could not expect to identify in the same study the optimal dose of droperidol for this setting; many more doses would have to be tested. The choice of our study groups was driven by two rationales. First, on the basis of the results of two previously published studies, there was a lack of evidence for dose responsiveness of antiemetic efficacy for droperidol regimens between 17 and 200 µg (i.e., 1.7–20 mg of droperidol per 100 mg of morphine) (2,3). Because there was some evidence that doses as small as 17 µg of droperidol per milligram of morphine were antiemetic (2), we aimed to test even smaller doses. Indeed, the smallest dose in our study, 5 µg of droperidol per milligram of morphine, has not been investigated before; that dose did not show any antiemetic efficacy, and this lack of efficacy was eventually crucial to establish dose responsiveness. There was no reasoning to test regimens more than 50 µg (i.e., 5 mg of droperidol per 100 mg of morphine) because there was evidence that >50% of the patients became drowsy or sedated with larger doses (3). Further, we wanted to test doses that were clearly distinct to increase the likelihood of establishing dose responsiveness with droperidol. Second, the no-treatment control group was chosen to estimate the emetic baseline risk in our study cohort and to identify with more confidence adverse events that were attributable to droperidol rather than to the morphine itself (for instance, sedation). From an ethical point of view, the no-treatment control was deemed acceptable because it corresponded to the usual clinical practice of most anesthesiologists in our institutions, because patients were free to withdraw from the trial at any time, and because antiemetic rescue treatment was available.

Droperidol may be regarded as the first-choice antiemetic for postoperative PCA with morphine; it is the only drug that has been tested in several randomized trials in the acute-pain PCA setting and that has shown consistent and clinically relevant antiemetic efficacy (2). The concern about potential droperidol-related cardiac toxicity (10) has to be taken seriously. These accusations, however, are controversial (11). There is evidence that similar symptoms (i.e., QT prolongation) may occur with many drugs that are currently used in anesthetic practice (12). Also, these accusations are likely to lead to an unjustified cessation of droperidol and a subsequent uncritical use of more expensive and perhaps less effective modern antiemetics (13). Many clinicians are certainly interested in the continued use of this inexpensive and effective antiemetic. Doses, however, should be kept to a minimum to decrease the likelihood of the occurrence of adverse drug reactions, both psychogenic and cardiac. The average morphine consumption was approximately 40 mg/24 hours; one patient consumed 130 mg. These data are in agreement with results from other PCA studies (1). Assuming that a regimen with droperidol 2.5 mg/100 mg of morphine was adopted, the average patient would receive 1 mg of droperidol per 24 hours, and the exceptional patient who consumed 130 mg of morphine per 24 hours would receive 3.25 mg of droperidol per 24 hours.

In conclusion, the smallest droperidol regimen tested in our trial, 5 µg per milligram of morphine, was neither antiemetic nor antipruritic and was not sedative. The medium dose, 15 µg, was not sedative, showed some antinausea efficacy, and was antipruritic. The largest dose tested, 50 µg, was clearly antiemetic; this dose, however, was no more antipruritic than 15 µg and was definitely sedative. Thus, we may assume that the optimal dose of droperidol, when added to a morphine PCA, is between 15 and 50 µg/mg of morphine (i.e., between 1.5 and 5 mg/100 mg of morphine). It may be that larger doses of droperidol would have a better antivomiting effect, but very likely at the price of even more sedation and perhaps further adverse drug effects.

	Acknowledgments

 
Dr. Tramèr is a recipient of a PROSPER grant (3233-051939.97/2) from the Swiss National Science Foundation.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Walder B, Schafer M, Henzi I, Tramèr MR. Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain: a quantitative systematic review. Acta Anaesthesiol Scand 2001; 45: 795–804.[ISI][Medline]
2. Tramèr MR, Walder B. Efficacy and adverse effects of prophylactic antiemetics during PCA therapy: a quantitative systematic review. Anesth Analg 1999; 88: 1354–61.[Abstract/Free Full Text]
3. Lamond CT, Robinson DL, Boyd JD, Cashman JN. 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]
4. Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect. BMJ 1995; 310: 452–4.[Free Full Text]
5. Altman D. Confidence intervals for the number needed to treat. BMJ 1998; 317: 1309–12.[Free Full Text]
6. Tramèr MR, Reynolds DJM, Moore RA, McQuay HJ. Efficacy, dose-response, and safety of ondansetron in prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized placebo-controlled trials. Anesthesiology 1997; 87: 1277–89.[ISI][Medline]
7. Henzi I, Sonderegger J, Tramèr MR. Efficacy, dose-response, and adverse effects of droperidol for prevention of postoperative nausea and vomiting. Can J Anaesth 2000; 47: 537–51.[Abstract/Free Full Text]
8. Kjellberg F, Tramèr MR. Pharmacological control of opioid-induced pruritus: a quantitative systematic review of randomized trials. Eur J Anaesthesiol 2001; 18: 346–57.[ISI][Medline]
9. Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA 1983; 249: 1743–5.[ISI][Medline]
10. Reilly JG, Ayis SA, Ferrier IN, et al. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet 2000; 355: 1048–52.[ISI][Medline]
11. White PF. Droperidol: a cost-effective antiemetic for over thirty years [editorial]. Anesth Analg 2002; 95: 789–90.[Free Full Text]
12. Wisely NA, Shipton EA. Long QT syndrome and anaesthesia. Eur J Anaesthesiol 2002; 19: 853–9.[ISI][Medline]
13. Tramèr MR, Reynolds DJ, Goodman NW. Whose drug is it anyway? Lancet 2001; 358: 1275.

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This Article Abstract Full Text (PDF) An erratum has been published Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Culebras, X. Articles by Tramèr, M. R. Search for Related Content PubMed PubMed Citation Articles by Culebras, X. Articles by Tramèr, M. R. Related Collections Pain Pharmacology

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999