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Prophylactic antiemetics for laparoscopic cholecystectomy: a comparison of perphenazine, droperidol plus ondansetron, and droperidol plus metoclopramide
Original Contributions Prophylactic Antiemetics for Laparoscopic Cholecystectomy: A Comparison of Perphenazine, Droperidol Plus Ondansetron, and Droperidol Plus Metoclopramide Richard A. Steinbrook, MD,* James L. Gosnell, RN,† Dubravka Freiberger, MD‡ Department of Anesthesia, Brigham and Women’s Hospital, and Department of Anaesthesia, Harvard Medical School, Boston, MA
Address correspondence to Dr. Steinbrook at the Department of Anesthesia, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115, USA.
Study Objective: To compare the prophylactic administration of ondansetron plus droperidol, droperidol plus metoclopramide, and perphenazine to determine effects on postoperative nausea, vomiting, and sedation after laparoscopic cholecystectomy. Design: Prospective, randomized, double-blind study. Setting: University medical center. Patients: 212 ASA physical status I and II adults presenting for laparoscopic cholecystectomy. Interventions: Patients were randomly assigned to receive one of three prophylactic antiemetic drug combinations: ondansetron 4 mg plus droperidol 0.625 mg (Group OD), droperidol 0.625 mg plus metoclopramide 10 mg (Group DM), or perphenazine 5 mg (Group P). Study drugs were administered intravenously after induction of general anesthesia. Measurements and Main Results: The groups were similar with respect to gender, age, weight, duration of surgery, numbers of patients receiving intraoperative atropine or ephedrine, number admitted overnight, and time to discharge home. Patients in Group P used lower total doses of opioids than did patients in Group OD. There were no significant differences in postoperative nausea, pain, or sedation scores, in numbers of patients requiring antiemetics (Group OD, 13 of 66; Group DM, 15 of 66; Group P, 14 of 68), or in numbers of patients vomiting, either in hospital or during the first postoperative day. Conclusions: These three drug regimens are equivalent for antiemetic prophylaxis before laparoscopic cholecystectomy. © 1998 by Elsevier Science Inc.
Received for publication February 4, 1998; revised manuscript accepted for publication July 1, 1998.
Keywords: Cholecystectomy; postoperative complications (nausea, vomiting); surgery, laparoscopic.
*Assistant Professor †Research Nurse ‡Instructor in Anaesthesia
Journal of Clinical Anesthesia 10:494 – 498, 1998 © 1998 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
0952-8180/98/$19.00 PII S0952-8180(98)00077-4
Antiemetics for laparoscopic cholecystectomy: Steinbrook et al.
Introduction Postoperative nausea and vomiting (PONV) remain significant problems after laparoscopic surgery.1 Even with prophylactic antiemetics, we have observed an incidence of PONV of 25% to 50% after laparoscopic cholecystectomy.2 Two recent studies have shown that the combination of two antiemetics with different mechanisms of action, ondansetron and droperidol, may be efficacious in preventing PONV. Pueyo et al.3 found the combination of ondansetron and droperidol to be more effective than either drug alone as antiemetic prophylaxis in women undergoing abdominal surgery. In women having laparoscopic tubal banding, McKenzie et al.4 found the ondansetron– droperidol combination to be superior to droperidol alone. In the present study of PONV after laparoscopic cholecystectomy, we compared the combination of ondansetron and droperidol with the combination of metoclopramide and droperidol, which we had previously found to be effective antiemetic prophylaxis for laparoscopic cholecystectomy.2 We also evaluated the efficacy of perphenazine, which Desilva et al.5 recently found to be the best prophylactic antiemetic for abdominal hysterectomy.
Materials and Methods With approval of the Brigham and Women’s Hospital’s Human Subjects Committee and written, informed consent, 212 patients scheduled for laparoscopic cholecystectomy were enrolled in a randomized, double-blind study. Patients were sedated preoperatively with intravenous (IV) midazolam (1 to 2 mg) and fentanyl [50 to 100 mg administered intravenously (IV)]. General anesthesia was induced with propofol (1.5 to 2.5 mg/kg IV) and cisatracurium (0.1 to 0.2 mg/kg IV). Immediately after tracheal intubation, patients received two 50 ml antiemetic drug infusions, either ondansetron 4 mg plus droperidol 0.625 mg (Group OD), droperidol 0.625 mg plus metoclopramide 10 mg (Group DM), or perphenazine 5 mg plus saline (Group P). Antiemetic drug preparation and randomization were performed by an unblinded research pharmacist, using a computer program to assign patient treatment blocks of six from a published table of random numbers;6 patients were stratified by gender-adjusted percent ideal body weight. Physicians, nurses, and patients were blinded to the identity of the antiemetics. Anesthesia was maintained with desflurane-air-oxygen and additional fentanyl and cisatracurium. Intraoperative bradycardia [heart rate ,50 beats per minute (bpm)] or hypotension (systolic blood pressure ,90 mmHg) were treated with atropine 0.4 mg IV or ephedrine 5 to 10 mg IV, respectively, at the discretion of the anesthesiologist. Ketorolac 30 mg IV was administered during skin closure. Neuromuscular block was antagonized with glycopyrrolate 0.6 to 1.0 mg and neostigmine 3.0 to 5.0 mg IV prior to extubation of the trachea. Postoperative pain was treated with IV fentanyl or IV morphine, as needed.
Patients were asked to rate their degree of nausea, pain, and sedation on a 10 cm visual analog scale (VAS) every 30 minutes while in the postanesthesia care unit (PACU). Postoperative antiemetics and opioids were administered at the discretion of the PACU nurse. Morphine 10 mg was considered equivalent to fentanyl 100 mcg. Patients were considered to be ready for discharge home when they were alert and oriented, had stable vital signs, were free of significant pain or nausea, were tolerating oral fluids, and were able to ambulate. All patients were contacted on the first postoperative day and questioned as to PONV after discharge. We anticipated that the rate of PONV would be decreased to approximately 20% with effective treatment. Power calculations were performed to determine whether the sample size was adequate to detect a situation in which the true rate of PONV associated with one of the treatments was as high as 40%, whereas that of the others was consistent with the 20% target. These calculations revealed that the study design provided 90% power to provide statistically significant results under these conditions. Statistical analyses were performed using StatView 4.01 (Abacus Concepts, Inc., Berkeley CA). Analysis of variance (ANOVA) and Chi-square tests were employed as appropriate. A p-value less than 0.05 was considered significant.
Results Twelve patients required conversion to open cholecystectomy and therefore were eliminated from the study; thus, 200 patients completed the protocol and are included in the analysis. The groups were similar with respect to gender, age, weight, duration of surgery, intraoperative fentanyl dose, and numbers receiving intraoperative atropine or ephedrine (Table 1). Postoperative nausea and vomiting data are shown in Figure 1. Numbers of patients receiving postoperative antiemetics were similar for all three groups. There were no significant differences in numbers who vomited, either in the PACU or during the first 24 hours after discharge. Mean VAS nausea scores were similar for patients in each group (Table 2). Pain and sedation data are presented in Table 3. Similar numbers of patients in each group received postoperative opioids; total doses were lower for patients in Group P than for patients in Group OD (p , 0.05, by ANOVA). Visual analog scale pain and sedation scores were similar. There were no significant differences in the number of patients admitted to hospital overnight, or in time to discharge home (for patients not admitted overnight). One patient from Group OD complained of feeling depressed immediately postoperatively; by the next day, she felt fine.
Discussion Prophylactic antiemetics are frequently administered before laparoscopic surgery because of the particularly high J. Clin. Anesth., vol. 10, September 1998
495
Original Contributions
Table 1. Patient Demographics and Intraoperative Data
n (M/F) Age (yrs) Weight (kg) Surgery time (min) Intraoperative fentanyl (mcg) atropine (n) ephedrine (n)
Group OD
Group DM
Group P
66 (12/54) 44 6 13 74 6 17 67 6 24
66 (12/54) 44 6 14 77 6 15 68 6 27
68 (15/53) 46 6 13 74 6 16 68 6 24
225 6 87 3 14
244 6 91 8 7
230 6 83 5 16
Note: Data are means 6 SD. There are no significant differences among the groups. Group OD 5 ondansetron plus droperidol; Group DM 5 droperidol plus metoclopramide; Group P 5 perphenazine.
incidence of PONV associated with this procedure.1,7 Nevertheless, PONV remains common8 and costly.9 Despite initial enthusiasm,10,11 ondansetron has not proved to be effective as prophylaxis against PONV following laparoscopic cholecystectomy2,12 or other abdominal surgical procedures.13–15 In our previous study, we found the combination of droperidol 0.625 mg IV with metoclopramide 10 mg IV to be more effective in preventing PONV than was ondansetron 4 mg IV in patients undergoing laparoscopic cholecystectomy.2 Recent studies by Pueyo et al.,3 McKenzie et al.,4 and Desilva et al.5 suggest that the combination of ondansetron and droperidol, or the administration of perphenazine alone, may be effective for antiemetic prophylaxis. In 360 women undergoing total abdominal hysterectomy, Desilva et al.5 compared ondansetron 4 mg, droperidol 1.25 mg, perphenazine 5 mg, metoclopramide 10 mg, and placebo. Although ondansetron, droperidol, and perphenazine all were effective antiemetics in this study,
ondansetron was associated with hypotension in 4 of 58 patients while 22% of droperidol treated patients were sedated. These authors concluded that perphenazine was the best choice for antiemetic prophylaxis. Because ondansetron and droperidol have different mechanisms of antiemetic activity, and because each alone is efficacious, the combination of the two is potentially advantageous. Pueyo et al.3 found the combination of ondansetron 4 mg and droperidol (2.5 mg followed by 1.25 mg 12 hours later) to be more effective than either drug alone or placebo in the prevention of PONV in women undergoing elective abdominal surgery. A similar conclusion was reached by McKenzie et al.,4 who compared droperidol 1.25 mg with ondansetron 4 mg to the same dose of droperidol with saline, in 120 healthy women undergoing laparoscopic tubal banding; the combination of droperidol and ondansetron was associated with a higher rate of complete response, fewer emetic episodes,
Figure 1. Postoperative nausea and vomiting. There were no significant differences in the numbers of patients receiving antiemetics in the postanesthesia care unit (PACU), or in the numbers who vomited, either in the PACU or up to 24 hours postoperatively. Group OD 5 ondansetron plus droperidol; Group DM 5 droperidol plus metoclopramide; Group P 5 perphenazine. 496
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Antiemetics for laparoscopic cholecystectomy: Steinbrook et al.
Table 2. Postoperative Nausea Scores (visual analog scale)
30 min 60 min 90 min 120 min 150 min 180 min 210 min 240 min
Group OD (n 5 66)
Group DM (n 5 66)
Group P (n 5 68)
0.3 6 0.9 0.5 6 1.6 0.4 6 1.3 0.3 6 1.1 0.2 6 0.9 0.3 6 1.5 0.2 6 0.9 0.1 6 0.6
0.6 6 1.9 0.4 6 1.4 0.3 6 1.2 0.4 6 1.2 0.4 6 1.5 0.4 6 1.6 0.2 6 0.6 0.1 6 0.3
0.3 6 1.2 0.3 6 0.9 0.1 6 0.3 0.3 6 1.2 0.1 6 0.7 0.1 6 0.6 0.1 6 0.6 0.2 6 0.6
Note: Data are means 6 SD. There are no significant differences among the groups. Group OD 5 ondansetron plus droperidol; Group DM 5 droperidol plus metoclopramide, Group P 5 perphenazine.
the prevention of PONV in 150 patients having major gynecologic surgery. The three antiemetic drug regimens we employed— ondansetron 4 mg plus droperidol 0.625, droperidol 0.625 mg plus metoclopramide 10 mg, and perphenazine 5 mg—were equivalent in terms of postoperative nausea, need for antiemetics, vomiting, sedation, and time to discharge. We cannot exclude the possibility that a larger study would find a significant difference between these drugs; however, even a statistically significant decrease in a larger study is unlikely to be of much clinical significance in view of our results. Pharmacy acquisition costs at the authors’ institution at the time of this writing for the antiemetics used in this study were as follows: ondansetron 4 mg, $14.51; droperidol 5 mg, $0.37; metoclopramide 10 mg, $0.27; perphenazine 5 mg, $4.40. Under the conditions of this study, with no apparent differences in terms of patient outcome, the cost advantage of droperidol plus metoclopramide makes this combination the best option for antiemetic prophylaxis before laparoscopic cholecystectomy.
and lower nausea scores. Belo and Koutsoukos,* however, found no differences between the combination of droperidol 1.25 mg plus ondansetron 4 mg and the same doses given alone in 80 women undergoing major gynecologic surgery. In a recent study by Fujii et al.,16 the combination of granisetron (a new 5-HT3 receptor antagonist) and droperidol was more effective than either drug alone for
Acknowledgments
*Belo S, Koutsoukos G: Combination of ondansetron and droperidol for antiemetic prophylaxis [Abstract]. Anesth Analg 1994;78:S30.
The authors wish to thank Terence Fenton, PhD, who provided assistance with the statistical analyses.
Table 3. Postoperative Pain and Sedation Group OD (n 5 66) Opioid in PACU (n) 55 Postoperative opioid 71 6 73 (fentanyl equivalents, mcg) Postoperative pain scores (visual analog scale) 30 min 4.2 6 2.6 60 min 4.3 6 2.1 90 min 3.7 6 1.8 120 min 3.4 6 1.9 150 min 3.2 6 1.9 180 min 2.7 6 1.8 210 min 2.8 6 1.8 240 min 2.6 6 2.0 Discharge time (min) (same 289 6 72 day only) Admitted overnight (n) 23 Postoperative sedation scores (visual analog scale) 30 min 6.6 6 1.7 60 min 5.3 6 1.7 90 min 4.6 6 1.7 120 min 4.1 6 1.9 150 min 3.6 6 1.9 180 min 2.9 6 1.8 210 min 2.6 6 1.9 240 min 1.9 6 2.0
Group DM (n 5 66)
Group P (n 5 68)
54 66 6 64
51 47 6 47*
4.5 6 2.5 3.8 6 2.1 3.7 6 2.0 3.3 6 2.0 3.1 6 2.1 3.3 6 2.2 3.1 6 2.2 2.8 6 1.9 283 6 87
4.3 6 2.6 4.2 6 2.0 3.8 6 1.8 3.4 6 1.7 3.1 6 1.7 2.8 6 1.4 2.6 6 1.5 2.7 6 1.6 295 6 93
16
25
6.7 6 1.6 5.6 6 1.7 4.7 6 1.9 4.2 6 2.1 3.5 6 2.0 3.3 6 2.3 2.5 6 1.8 2.3 6 1.9
7.0 6 1.4 6.1 6 1.6 5.4 6 1.7 4.6 6 1.8 4.1 6 1.7 3.5 6 1.8 3.1 6 1.9 2.9 6 1.9
Note: Data are means 6 SD. Group OD 5 ondansetron plus droperidol; Group DM 5 droperidol plus metoclopramide; Group P 5 perphenazine; PACU 5 postanesthesia care unit. *p , 0.05 compared with Group OD (ANOVA). J. Clin. Anesth., vol. 10, September 1998
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Original Contributions
References 1. Shankar KB, Steinbrook RA: Anesthetic considerations for minimally invasive surgery. In: Brooks DC (ed): Current Review of Minimally Invasive Surgery. Philadelphia: Current Science, 1998: 29 – 40. 2. Steinbrook RA, Freiberger D, Gosnell JL, Brooks DC: Prophylactic antiemetics for laparoscopic cholecystectomy: ondansetron versus droperidol plus metoclopramide. Anesth Analg 1996;83: 1081–3. 3. Pueyo FJ, Carrascosa F, Lopez L, Iribarren MJ, Garcia-Pedrajas F, Saez A: Combination of ondansetron and droperidol in the prophylaxis of postoperative nausea and vomiting. Anesth Analg 1996;83:117–22. 4. McKenzie R, Uy NT, Riley TJ, Hamilton DL: Droperidol/ondansetron combination controls nausea and vomiting after tubal banding. Anesth Analg 1996;83:1218 –22. 5. Desilva PH, Darvish AH, McDonald SM, Cronin MK, Clark K: The efficacy of prophylactic ondansetron, droperidol, perphenazine, and metoclopramide in the prevention of nausea and vomiting after major gynecologic surgery. Anesth Analg 1995;81:139 – 43. 6. Diem K, Lentner C (eds): Documenta Geigy, scientific tables, 7th ed. Basel, Switzerland: Ciba-Geigy, 1970:131. 7. Watcha MF, White PF: Postoperative nausea and vomiting. Its etiology, treatment, and prevention. Anesthesiology 1992;77:162– 84. 8. Kapur PA: The big “little problem.” Anesth Analg 1991;73:243–5. 9. Carroll NV, Miederhoff PA, Cox FM, Hirsch JD: Costs incurred by
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outpatient surgical centers in managing postoperative nausea and vomiting. J Clin Anesth 1994;6:364 –9. Leeser J, Lip H: Prevention of postoperative nausea and vomiting using ondansetron, a new, selective, 5-HT3 receptor antagonist. Anesth Analg 1991;72:751–5. McKenzie R, Kovac A, O’Connor T, et al: Comparison of ondansetron versus placebo to prevent postoperative nausea and vomiting in women undergoing ambulatory gynecologic surgery. Anesthesiology 1993;78:21– 8. Koivuranta MK, La¨a¨ra¨ E, Ryha¨nen PT: Antiemetic efficacy of prophylactic ondansetron in laparoscopic cholecystectomy. A randomized, double-blind, placebo-controlled trial. Anaesthesia 1996;51:52–5. Grond S, Lynch J, Diefenbach C, Altrock K, Lehmann KA: Comparison of ondansetron and droperidol in the prevention of nausea and vomiting after inpatient minor gynecologic surgery. Anesth Analg 1995;81:603–7. Tang J, Watcha MF, White PF: A comparison of costs and efficacy of ondansetron and droperidol as prophylactic antiemetic therapy for elective outpatient gynecologic procedures. Anesth Analg 1996;83:304 –13. Campbell C, Miller DD: Failure of ondansetron to control postoperative nausea and vomiting in ambulatory surgical patients. Am J Anesthesiol 1995;22:81– 6. Fujii Y, Toyooka H, Tanaka H: Prevention of postoperative nausea and vomiting with a combination of granisetron and droperidol. Anesth Analg 1998;86:613– 6.
Address correspondence to Dr. Steinbrook at the Department of Anesthesia, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115, USA.
Study Objective: To compare the prophylactic administration of ondansetron plus droperidol, droperidol plus metoclopramide, and perphenazine to determine effects on postoperative nausea, vomiting, and sedation after laparoscopic cholecystectomy. Design: Prospective, randomized, double-blind study. Setting: University medical center. Patients: 212 ASA physical status I and II adults presenting for laparoscopic cholecystectomy. Interventions: Patients were randomly assigned to receive one of three prophylactic antiemetic drug combinations: ondansetron 4 mg plus droperidol 0.625 mg (Group OD), droperidol 0.625 mg plus metoclopramide 10 mg (Group DM), or perphenazine 5 mg (Group P). Study drugs were administered intravenously after induction of general anesthesia. Measurements and Main Results: The groups were similar with respect to gender, age, weight, duration of surgery, numbers of patients receiving intraoperative atropine or ephedrine, number admitted overnight, and time to discharge home. Patients in Group P used lower total doses of opioids than did patients in Group OD. There were no significant differences in postoperative nausea, pain, or sedation scores, in numbers of patients requiring antiemetics (Group OD, 13 of 66; Group DM, 15 of 66; Group P, 14 of 68), or in numbers of patients vomiting, either in hospital or during the first postoperative day. Conclusions: These three drug regimens are equivalent for antiemetic prophylaxis before laparoscopic cholecystectomy. © 1998 by Elsevier Science Inc.
Received for publication February 4, 1998; revised manuscript accepted for publication July 1, 1998.
Keywords: Cholecystectomy; postoperative complications (nausea, vomiting); surgery, laparoscopic.
*Assistant Professor †Research Nurse ‡Instructor in Anaesthesia
Journal of Clinical Anesthesia 10:494 – 498, 1998 © 1998 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
0952-8180/98/$19.00 PII S0952-8180(98)00077-4
Antiemetics for laparoscopic cholecystectomy: Steinbrook et al.
Introduction Postoperative nausea and vomiting (PONV) remain significant problems after laparoscopic surgery.1 Even with prophylactic antiemetics, we have observed an incidence of PONV of 25% to 50% after laparoscopic cholecystectomy.2 Two recent studies have shown that the combination of two antiemetics with different mechanisms of action, ondansetron and droperidol, may be efficacious in preventing PONV. Pueyo et al.3 found the combination of ondansetron and droperidol to be more effective than either drug alone as antiemetic prophylaxis in women undergoing abdominal surgery. In women having laparoscopic tubal banding, McKenzie et al.4 found the ondansetron– droperidol combination to be superior to droperidol alone. In the present study of PONV after laparoscopic cholecystectomy, we compared the combination of ondansetron and droperidol with the combination of metoclopramide and droperidol, which we had previously found to be effective antiemetic prophylaxis for laparoscopic cholecystectomy.2 We also evaluated the efficacy of perphenazine, which Desilva et al.5 recently found to be the best prophylactic antiemetic for abdominal hysterectomy.
Materials and Methods With approval of the Brigham and Women’s Hospital’s Human Subjects Committee and written, informed consent, 212 patients scheduled for laparoscopic cholecystectomy were enrolled in a randomized, double-blind study. Patients were sedated preoperatively with intravenous (IV) midazolam (1 to 2 mg) and fentanyl [50 to 100 mg administered intravenously (IV)]. General anesthesia was induced with propofol (1.5 to 2.5 mg/kg IV) and cisatracurium (0.1 to 0.2 mg/kg IV). Immediately after tracheal intubation, patients received two 50 ml antiemetic drug infusions, either ondansetron 4 mg plus droperidol 0.625 mg (Group OD), droperidol 0.625 mg plus metoclopramide 10 mg (Group DM), or perphenazine 5 mg plus saline (Group P). Antiemetic drug preparation and randomization were performed by an unblinded research pharmacist, using a computer program to assign patient treatment blocks of six from a published table of random numbers;6 patients were stratified by gender-adjusted percent ideal body weight. Physicians, nurses, and patients were blinded to the identity of the antiemetics. Anesthesia was maintained with desflurane-air-oxygen and additional fentanyl and cisatracurium. Intraoperative bradycardia [heart rate ,50 beats per minute (bpm)] or hypotension (systolic blood pressure ,90 mmHg) were treated with atropine 0.4 mg IV or ephedrine 5 to 10 mg IV, respectively, at the discretion of the anesthesiologist. Ketorolac 30 mg IV was administered during skin closure. Neuromuscular block was antagonized with glycopyrrolate 0.6 to 1.0 mg and neostigmine 3.0 to 5.0 mg IV prior to extubation of the trachea. Postoperative pain was treated with IV fentanyl or IV morphine, as needed.
Patients were asked to rate their degree of nausea, pain, and sedation on a 10 cm visual analog scale (VAS) every 30 minutes while in the postanesthesia care unit (PACU). Postoperative antiemetics and opioids were administered at the discretion of the PACU nurse. Morphine 10 mg was considered equivalent to fentanyl 100 mcg. Patients were considered to be ready for discharge home when they were alert and oriented, had stable vital signs, were free of significant pain or nausea, were tolerating oral fluids, and were able to ambulate. All patients were contacted on the first postoperative day and questioned as to PONV after discharge. We anticipated that the rate of PONV would be decreased to approximately 20% with effective treatment. Power calculations were performed to determine whether the sample size was adequate to detect a situation in which the true rate of PONV associated with one of the treatments was as high as 40%, whereas that of the others was consistent with the 20% target. These calculations revealed that the study design provided 90% power to provide statistically significant results under these conditions. Statistical analyses were performed using StatView 4.01 (Abacus Concepts, Inc., Berkeley CA). Analysis of variance (ANOVA) and Chi-square tests were employed as appropriate. A p-value less than 0.05 was considered significant.
Results Twelve patients required conversion to open cholecystectomy and therefore were eliminated from the study; thus, 200 patients completed the protocol and are included in the analysis. The groups were similar with respect to gender, age, weight, duration of surgery, intraoperative fentanyl dose, and numbers receiving intraoperative atropine or ephedrine (Table 1). Postoperative nausea and vomiting data are shown in Figure 1. Numbers of patients receiving postoperative antiemetics were similar for all three groups. There were no significant differences in numbers who vomited, either in the PACU or during the first 24 hours after discharge. Mean VAS nausea scores were similar for patients in each group (Table 2). Pain and sedation data are presented in Table 3. Similar numbers of patients in each group received postoperative opioids; total doses were lower for patients in Group P than for patients in Group OD (p , 0.05, by ANOVA). Visual analog scale pain and sedation scores were similar. There were no significant differences in the number of patients admitted to hospital overnight, or in time to discharge home (for patients not admitted overnight). One patient from Group OD complained of feeling depressed immediately postoperatively; by the next day, she felt fine.
Discussion Prophylactic antiemetics are frequently administered before laparoscopic surgery because of the particularly high J. Clin. Anesth., vol. 10, September 1998
495
Original Contributions
Table 1. Patient Demographics and Intraoperative Data
n (M/F) Age (yrs) Weight (kg) Surgery time (min) Intraoperative fentanyl (mcg) atropine (n) ephedrine (n)
Group OD
Group DM
Group P
66 (12/54) 44 6 13 74 6 17 67 6 24
66 (12/54) 44 6 14 77 6 15 68 6 27
68 (15/53) 46 6 13 74 6 16 68 6 24
225 6 87 3 14
244 6 91 8 7
230 6 83 5 16
Note: Data are means 6 SD. There are no significant differences among the groups. Group OD 5 ondansetron plus droperidol; Group DM 5 droperidol plus metoclopramide; Group P 5 perphenazine.
incidence of PONV associated with this procedure.1,7 Nevertheless, PONV remains common8 and costly.9 Despite initial enthusiasm,10,11 ondansetron has not proved to be effective as prophylaxis against PONV following laparoscopic cholecystectomy2,12 or other abdominal surgical procedures.13–15 In our previous study, we found the combination of droperidol 0.625 mg IV with metoclopramide 10 mg IV to be more effective in preventing PONV than was ondansetron 4 mg IV in patients undergoing laparoscopic cholecystectomy.2 Recent studies by Pueyo et al.,3 McKenzie et al.,4 and Desilva et al.5 suggest that the combination of ondansetron and droperidol, or the administration of perphenazine alone, may be effective for antiemetic prophylaxis. In 360 women undergoing total abdominal hysterectomy, Desilva et al.5 compared ondansetron 4 mg, droperidol 1.25 mg, perphenazine 5 mg, metoclopramide 10 mg, and placebo. Although ondansetron, droperidol, and perphenazine all were effective antiemetics in this study,
ondansetron was associated with hypotension in 4 of 58 patients while 22% of droperidol treated patients were sedated. These authors concluded that perphenazine was the best choice for antiemetic prophylaxis. Because ondansetron and droperidol have different mechanisms of antiemetic activity, and because each alone is efficacious, the combination of the two is potentially advantageous. Pueyo et al.3 found the combination of ondansetron 4 mg and droperidol (2.5 mg followed by 1.25 mg 12 hours later) to be more effective than either drug alone or placebo in the prevention of PONV in women undergoing elective abdominal surgery. A similar conclusion was reached by McKenzie et al.,4 who compared droperidol 1.25 mg with ondansetron 4 mg to the same dose of droperidol with saline, in 120 healthy women undergoing laparoscopic tubal banding; the combination of droperidol and ondansetron was associated with a higher rate of complete response, fewer emetic episodes,
Figure 1. Postoperative nausea and vomiting. There were no significant differences in the numbers of patients receiving antiemetics in the postanesthesia care unit (PACU), or in the numbers who vomited, either in the PACU or up to 24 hours postoperatively. Group OD 5 ondansetron plus droperidol; Group DM 5 droperidol plus metoclopramide; Group P 5 perphenazine. 496
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Antiemetics for laparoscopic cholecystectomy: Steinbrook et al.
Table 2. Postoperative Nausea Scores (visual analog scale)
30 min 60 min 90 min 120 min 150 min 180 min 210 min 240 min
Group OD (n 5 66)
Group DM (n 5 66)
Group P (n 5 68)
0.3 6 0.9 0.5 6 1.6 0.4 6 1.3 0.3 6 1.1 0.2 6 0.9 0.3 6 1.5 0.2 6 0.9 0.1 6 0.6
0.6 6 1.9 0.4 6 1.4 0.3 6 1.2 0.4 6 1.2 0.4 6 1.5 0.4 6 1.6 0.2 6 0.6 0.1 6 0.3
0.3 6 1.2 0.3 6 0.9 0.1 6 0.3 0.3 6 1.2 0.1 6 0.7 0.1 6 0.6 0.1 6 0.6 0.2 6 0.6
Note: Data are means 6 SD. There are no significant differences among the groups. Group OD 5 ondansetron plus droperidol; Group DM 5 droperidol plus metoclopramide, Group P 5 perphenazine.
the prevention of PONV in 150 patients having major gynecologic surgery. The three antiemetic drug regimens we employed— ondansetron 4 mg plus droperidol 0.625, droperidol 0.625 mg plus metoclopramide 10 mg, and perphenazine 5 mg—were equivalent in terms of postoperative nausea, need for antiemetics, vomiting, sedation, and time to discharge. We cannot exclude the possibility that a larger study would find a significant difference between these drugs; however, even a statistically significant decrease in a larger study is unlikely to be of much clinical significance in view of our results. Pharmacy acquisition costs at the authors’ institution at the time of this writing for the antiemetics used in this study were as follows: ondansetron 4 mg, $14.51; droperidol 5 mg, $0.37; metoclopramide 10 mg, $0.27; perphenazine 5 mg, $4.40. Under the conditions of this study, with no apparent differences in terms of patient outcome, the cost advantage of droperidol plus metoclopramide makes this combination the best option for antiemetic prophylaxis before laparoscopic cholecystectomy.
and lower nausea scores. Belo and Koutsoukos,* however, found no differences between the combination of droperidol 1.25 mg plus ondansetron 4 mg and the same doses given alone in 80 women undergoing major gynecologic surgery. In a recent study by Fujii et al.,16 the combination of granisetron (a new 5-HT3 receptor antagonist) and droperidol was more effective than either drug alone for
Acknowledgments
*Belo S, Koutsoukos G: Combination of ondansetron and droperidol for antiemetic prophylaxis [Abstract]. Anesth Analg 1994;78:S30.
The authors wish to thank Terence Fenton, PhD, who provided assistance with the statistical analyses.
Table 3. Postoperative Pain and Sedation Group OD (n 5 66) Opioid in PACU (n) 55 Postoperative opioid 71 6 73 (fentanyl equivalents, mcg) Postoperative pain scores (visual analog scale) 30 min 4.2 6 2.6 60 min 4.3 6 2.1 90 min 3.7 6 1.8 120 min 3.4 6 1.9 150 min 3.2 6 1.9 180 min 2.7 6 1.8 210 min 2.8 6 1.8 240 min 2.6 6 2.0 Discharge time (min) (same 289 6 72 day only) Admitted overnight (n) 23 Postoperative sedation scores (visual analog scale) 30 min 6.6 6 1.7 60 min 5.3 6 1.7 90 min 4.6 6 1.7 120 min 4.1 6 1.9 150 min 3.6 6 1.9 180 min 2.9 6 1.8 210 min 2.6 6 1.9 240 min 1.9 6 2.0
Group DM (n 5 66)
Group P (n 5 68)
54 66 6 64
51 47 6 47*
4.5 6 2.5 3.8 6 2.1 3.7 6 2.0 3.3 6 2.0 3.1 6 2.1 3.3 6 2.2 3.1 6 2.2 2.8 6 1.9 283 6 87
4.3 6 2.6 4.2 6 2.0 3.8 6 1.8 3.4 6 1.7 3.1 6 1.7 2.8 6 1.4 2.6 6 1.5 2.7 6 1.6 295 6 93
16
25
6.7 6 1.6 5.6 6 1.7 4.7 6 1.9 4.2 6 2.1 3.5 6 2.0 3.3 6 2.3 2.5 6 1.8 2.3 6 1.9
7.0 6 1.4 6.1 6 1.6 5.4 6 1.7 4.6 6 1.8 4.1 6 1.7 3.5 6 1.8 3.1 6 1.9 2.9 6 1.9
Note: Data are means 6 SD. Group OD 5 ondansetron plus droperidol; Group DM 5 droperidol plus metoclopramide; Group P 5 perphenazine; PACU 5 postanesthesia care unit. *p , 0.05 compared with Group OD (ANOVA). J. Clin. Anesth., vol. 10, September 1998
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Original Contributions
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