Summary

Background and objectives: This study was designed to investigate whether single epidural droperidol or continuous epidural droperidol inhibit pruritus and postoperative nausea and vomiting induced by postoperative continuous epidural fentanyl administration, and to identify the optimal method of administering epidural droperidol. Methods: 120 ASA I–II patients undergoing subtotal gastrectomy with general anaesthesia combined with epidural anaesthesia were randomly allocated into three groups: control (no droperidol), single injection (droperidol 2.5 mg) and continuous group (droperidol 2.5 mg 2 day−1). Postoperatively the frequency and severity of pruritus and postoperative nausea and vomiting in all groups were compared during 48 h. Results: The frequency and severity of pruritus was significantly lower in both single injection and continuous groups than control group after epidural fentanyl administration (P < 0.05). The frequency and severity of postoperative nausea and vomiting was significantly lower in single injection group than control group after epidural fentanyl administration (P < 0.05). Conclusion: Epidural continuous droperidol is effective for reducing pruritus, and single epidural droperidol injection is effective for reducing pruritus and postoperative nausea and vomiting induced by postoperative continuous epidural fentanyl analgesia.

Background and objective Numerous drugs have been used to prevent or to treat opioid-induced pruritus in the surgical setting. Their relative efficacy is not well understood.

Methods The methods employed involved the systematic search (MEDLINE, EMBASE, Cochrane library, bibliographies, without language restriction, up to June 2000) for full reports of randomized comparisons of any intervention which is thought to be anti–pruritic (active) compared with placebo or no treatment (control) in surgical (including labour) patients receiving opioids. The number of patients who had no pruritus were analysed using relative risk and number–neededto– treat with 95% confidence interval.

Results Twenty-two trials (1477 patients) were analysed. Two trials (66 patients), both with low-dose propofol, were on treatment of established pruritus; propofol had no anti-pruritic effect compared with Intralipid. In prophylaxis trials, the average incidence of pruritus with control was 59% (range, 10% to 100%). Most mu–receptor antagonists were efficacious: intravenous naloxone 0.25–2.4 μgkg−1 h−1, relative risk 2.31 (95% confidence interval, 1.5 to 3.54), numberneeded– to–treat to prevent pruritus compared with control 3.5; oral naltrexone 9 mg, relative risk 2.80 (1.35–5.80), number-needed-to-treat 1.7; naltrexone 6mg was less effective and 3mg did not work; different intravenous and epidural nalbuphine regimens, relative risk 1.71 (1.12–2.62), number-needed-to-treat 4.2. Intravenous nalmefene 0.5 or 1mg was not antipruritic. Intravenous (but not epidural) droperidol 2.5mg was efficacious, relative risk, 1.71 (1.28–2.29), number-needed-to-treat 4.9. There was a lack of evidence for any anti–pruritic efficacy with prophylactic propofol, epidural or intrathecal epinephrine, epidural clonidine, epidural prednisone, intravenous ondansetron, or intramuscular hydroxyzine.

Conclusion Naloxone, naltrexone, nalbuphine and droperidol are efficacious in the prevention of opioidinduced pruritus; minimal effective doses remain unknown. There is a lack of valid data on the efficacy of interventions for the treatment of established pruritus.

We conducted a prospective, randomized, double-blind clinical trial comparing droperidol 1.25 mg intravenously (i.v.) (group 1, n = 30), ondansetron 4 mg i.v. (group 2, n = 30), or both (group 3, n = 30) in the prevention of postoperative nausea and vomiting (PONV) in the first 24 h following major gynaecological procedures under combined general and epidural anaesthesia. PONV was analysed by a linear nausea/vomiting score, incidence of nausea and vomiting, and the need for antiemetic rescue. Our results showed a similar incidence of nausea and vomiting in all groups (G1 33%, G2 40%, G3 43%). However, when comparisons were made according to the time of assessment, combination therapy resulted in significantly lower PONV than droperidol in the first hour (0% vs. 13%, P < 0.05) and second hour (0% vs. 13%, P < 0.05), and than ondansetron on the first hour (0% vs. 13%, P < 0.05). A trend persisted up to the fourth hour but was not statistically significant in either group. In conclusion, droperidol and ondansetron are effective agents in the prevention of PONV, and their combination seems to provide slightly better results than either drug alone.

Postoperative nausea and vomiting (PONV) is a common adverse phenomenon following breast surgery. The efficacy of ondansetron and droperidol in preventing post–operative nausea and vomiting in women undergoing breast surgery was compared in this randomized, double–blind, placebo–controlled study. Altogether 207 women were randomly assigned to receive either a single intravenous dose of droperidol (1.25 mg) (n = 69), ondansetron (8 mg) (n = 67) or saline (n = 71) immediately after induction of general anaesthesia with thiopental, fentanyl, atracurium, nitrous oxide in oxygen and isoflurane. Complaints of nausea, vomiting and requests for rescue antiemetics were recorded during a 24-h period postoperatively. During the initial 2 h in the postanaesthesia care unit, the incidence of postoperative nausea and vomiting was 15%, 6% and 12% in the placebo, droperidol and ondansetron groups, respectively (NS). The incidence of post–operative nausea and vomiting during the first 24 h was 61%, 48% and 45% in the placebo, droperidol and ondansetron treatment groups, respectively (NS). Postoperative analgesic requirements and the length of stay in the post–anaesthesia care unit were equal in all three treatment groups. It is concluded that the intravenous pretreatment with single doses of ondansetron or droperidol did not substantially prevent postoperative nausea and vomiting after breast surgery.

We investigated the effect of a small dose of midazolam, ketamine, droperidol or lidocaine on the propofol dose required for hypnosis during induction of general anaesthesia. These drugs were randomly administered to 100 patients about to undergo scheduled surgery. Propofol was then infused at a rate of 250 μg kg−1 min−1 and the hypnotic dose to produce hypnosis was evaluated. Midazolam (20 μg kg−1) and droperidol (20 μg kg−1) significantly reduced the mean hypnotic dose of propofol (mean) S.D.) compared with the placebo (43.7 ± 17.8 mg, 61.9 ± 10.6 mg and 72.5 ± 27.7 mg after pretreatment with midazolam, droperidol and placebo, respectively), whereas ketamine (0.1 mg kg−1) and lidocaine (1 mg kg−1) did not significantly affect the hypnotic dose of propofol (63.1 ± 25.6 mg and 65.1 ± 24.8 mg, respectively). Only midazolam when compared with saline administration, (176 ± 66s and 298 ± 126s, respectively), shortened the time to achieve hypnosis. The changes in blood pressure (non-invasive) and heart rate were not significantly different in all groups during the induction of anaesthesia and oro-tracheal intubation. These results raise the possibility that new combinations of central nervous system drugs, such as droperidol and propofol, have a potential to reduce the dose of intravenous anaesthetics, including propofol, that produce hypnosis without significant adverse effects.

The anti-emetic effects of ondansetron and droperidol were evaluated in 134 ASA Grade I and II female patients, scheduled for laparoscopic cholecystectomy and minor gynaecological laparoscopic surgery, who were randomly assigned to receive ondansetron 4 mg or droperidol 75 μg kg−1 intravenously immediately after induction of anaesthesia. The patients were assessed 1, 6, 12 and 24 h after surgery for intensity of nausea and number of vomiting episodes. In the case of the patients undergoing laparoscopy, vomiting episodes occurred in a similar proportion in patients treated with ondansetron or droperidol, with the probability of the Type I error of 0.05 and the Type error II of 0.1. Although there was no difference between the two groups in emetic episodes following all laparoÍscopic procedures and gynaecological laparoscopic surgery, there was a significant difference between these parameters after laparoscopic cholecystectomy. The patients treated with ondansetron experienced a lower intensity of nausea (P=0.04) after laparoscopic cholecystectomy, less frequent severe nausea (P=0.02) and episodes of vomiting (P=0.04) when compared with those in the droperidol group. We conclude, that despite the result the droperidol prophylaxis appears to be an effective alternative to ondansetron in all patients undergoing laparoscopy, the ondansetron prophylaxis is superior to droperidol in patients undergoing laparoscopic cholecystectomy.

We have compared the efficacy and safety of combined granisetron and droperidol with each anti-emetic alone for preventing post-operative nausea and vomiting after thyroidectomy. In a prospective, randomized, double-blind study, 180 women received granisetron 40 μg kg−1, droperidol 20 μg kg−1, or granisetron 40 μg kg−1 plus droperidol 20 μg kg−1 (n=60 of each) intravenously immediately before induction of anaesthesia. A standard general anaesthetic technique and post-operative analgesia were used. A complete response, defined as no post-operative nausea and vomiting and no need for another rescue anti-emetic, during the first 24 h after anaesthesia occurred in 88%, 60% and 98% of patients who had received granisetron, droperidol and granisetron plus droperidol (P< 0.05; overall Fisher's exact probability test). No clinically important adverse events due to the drugs were observed in any of the groups. In summary, prophylactic use of combined granisetron and droperidol is more effective than each drug alone for the prevention of post-operative nausea and vomiting in female patients undergoing thyroidectomy.

Post-operative nausea and vomiting is distressing for patients and can cause dissatisfaction and impaired well-being in the post-operative period. This study examined the question whether the reduced incidence of post-operative nausea and vomiting inevitably translates into improved clinical status and well-being. In this context high doses of droperidol were investigated. On the one hand, droperidol is known to be a powerful anti-emetic, but on the other hand there is concern about psychological effects, both in the pre- and the post-operative period. In this prospective randomized double-blinded study, droperidol (5–7.5 mg) was compared with midazolam (5–7.5 mg) used to supplement fentanyl-N2</O based anaesthesia, with respect to post-operative mood and well-being using a psychological questionnaire (Bf-S-test). Furthermore, the incidence of post-operative nausea and vomiting was recorded. Out of 160 patients undergoing thyroidectomy and laparoscopic cholecystectomy, data from 150 patients were analysed. The administration of droperidol significantly lowered the incidence of post-operative nausea and vomiting from 77.8% to 55.1% compared with midazolam (P=0.0059; χ2-test). Although post-operative nausea and vomiting is an independent risk factor for post-operative discomfort and bad mood, patients receiving droperidol showed impaired well-being 6 h after surgery. Well-being scores returned to pre-operative base-line values and did not differ between the two groups 24 and 48 h post-operatively. The reduced incidence of post-operative nausea and vomiting achieved with high dose droperidol does not equate with increased post-operative well-being. It is an important point at issue to decide whether smaller doses of droperidol that are commonly used for anti-emetic therapy are free of these side effects.

A double-blind randomized study was performed in 100 patients undergoing thyroidectomy to evaluate the effect of positive therapeutic suggestions made during neurolept-anaesthesia. The classic droperidol-fentanyl-N2O technique was used as these drugs preserve the neurophysiological functions required to process the information in the therapeutic suggestions given during general anaesthesia. Patients in the suggestion group heard positive non-affirmative suggestions during the whole operation. An autoreverse tape player was used. The control group listened to an empty tape. Both groups were comparable with respect to demographic variables, anaesthetic technique, drug dosage, duration of anaesthesia and surgery. Patients in the suggestion group suffered significantly less from post-operative nausea or volumiting (suggestion: 47.2% vs. control: 85.7%) and required less anti-emetic treatment (suggestion: 30.6% vs. control: 68.6%). We conclude that therapeutic suggestions heard during neurolept-anaesthesia are processed and decrease post-operative nausea and vomiting in patients after thyroidectomy.

Eighty patients were recruited into a double-blind, randomized trial to find the optimal dose of droperidol for addition to the patient-controlled analgesia (PCA) morphine infusate for female patients undergoing gynaecological surgery. A standardized anaesthetic technique was employed. Post-operative analgesia was provided by PCA morphine. Patients were allocated at random into one of four treatment groups receiving with each PCA morphine bolus: (1) droperidol 0.05 mg; (2) droperidol 0.10 mg; (3) droperidol 0.15 mg; and (4) droperidol 0.20 mg, respectively. The incidence of post-operative nausea and vomiting (PONV), requests for rescue anti-emetic medication, and incidence of side effects were recorded. The number of symptom-free patients in each group increased as the droperidol dose increased, but although there was a significant inverse association between the total dose of droperidol received and the severity of PONV (P<0.05), there were no significant differences between individual groups. In each group, patients were significantly less sedated at 24 h compared with 12 h (P<0.01). However, after 24 h, patients in group 4 were significantly more sedated than patients in groups 1 and 2 (P<0.05). There were no significant differences between the groups in terms of the incidence of anxiety or other side effects attributable to droperidol. The present authors suggest that, although the results demonstrate few statistically significant differences between the four groups, a PCA bolus dose of droperidol of 0.10 mg mL−1 appears to provide the optimal balance between anti-emetic efficacy and an acceptable incidence of side effects.

This study evaluates the prophylactic anti-emetic efficacy of granisetron, droperidol and metoclopramide, for the prevention of post-operative nausea and vomiting in female patients undergoing elective laparoscopic cholecystectomy. The patients were randomly assigned to one of four groups (n=30 for each group): granisetron 3 mg, droperidol 1.25 mg, metoclopramide 10 mg and placebo (saline). These medications were given immediately before the induction of anaesthesia. During the first 24 h after an-aesthesia, the incidence of post-operative nausea and vomiting was 13, 30, 33 and 37% after administration of granisetron, droperidol, metoclopramide and placebo, respectively (P>0.05, overall Fisher's exact probability test). No clinically important adverse effects were observed in either group. Our results suggest that granisetron is a better anti-emetic than droperidol or metoclopramide for the prevention of post-operative nausea and vomiting after laparoscopic cholecystectomy when compared with a placebo.

The molecular effects of droperidol (C22H22FN3O2) on single sodium channels from the human brain were investigated using the electrophysiological planar lipid-bilayer technique. Droperidol (0.05–0.8 mm) induced a concentration dependent and voltage independent reduction in the time averaged single channel conductance by two mechanisms: a reduction in the fractional channel open time (major effect, approximately 90%) and a decrease in the channel amplitude (minor effect). The weighted computer fit of the concentration response for the combined effect curve yielded an EC50 of 0.68 mm droperidol and a maximal conductance block of 77%. These blocking effects of droperidol on CNS sodium channels occurred at a concentration range comparable with other specific anaesthetic compounds but far beyond clinical serum levels (up to 0.002 mm). Therefore in contrast with animal preparations (frog peripheral nerve, sodium channel) the human brain sodium channel is not a major target site for droperidol during clinical anaesthesia.

In this study the antiemetic effects of droperidol, ondansetron and their combination were evaluated in 160 ASA Grade I and II children undergoing surgery for strabismus, who were randomly assigned to one of four groups: Group D received droperidol 75 μg kg−1, group O ondansetron 0.1 mg kg−1, group D + O received both droperidol 75 μg kg−1 and ondansetron 0.1 mg kg−1, and group N NaCl as placebo. Emesis within the first 24 h occurred in 95.0% of the children with placebo medication, compared with 32.5% (D), 40.0% (O) and 45.0% (D + O) in the groups with antiemetic prophylaxis. The differences between group N and all other groups were significant (P < 0.001). However, there were no statistically significant differences between the groups D, O and D + O. It is concluded that droperidol (75 μg kg−1) and ondansetron (0.1 mg kg−1) both significantly reduce PONV in children undergoing surgery for strabismus. Neither ondansetron, nor the combination D+O were superior to droperidol alone.

To compare the efficacy in the treatment of post-operative nausea and/or vomiting (PONV), 75 patients undergoing gynaecological procedures under general anaesthesia using N2O/enflurane who suffered from PONV in the first hour after surgery were randomly allocated to three groups containing 25 patients each to receive either alizapride 100 mg, droperidol 1mg or ondansetron 8mg (i.v.). Patients expressed the severity of their nausea on a Visual Analogue Scale (VAS) ranging from 0 (none) to 10 (as bad as possible). Vomiting was recorded as present or absent, and the number of emetic events was noted. Data were recorded until rescue medication was given or until 4 h after the administration of the study drug. There were no significant differences between the three groups in the average VAS scores and the presence of vomiting at the time of entry into the study. Fifteen and 30 min after the administration of the study drug, VAS decreased notably in all groups. This decrease was similar and statistically significant within each group. However, comparison between the three groups showed no statistically significant differences. There was no statistically significant difference between the three groups in the number of patients receiving rescue medication, the number of emetic events and the time from administration of the study drug until rescue medication was given. It is concluded that alizapride 100 mg, droperidol 1mg and ondansetron 8mg intravenously are equally effective in the treatment of PONV after gynaecological procedures and that the newer drugs alizapride and ondansetron offer no advantage over droperidol.