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PubMed2007

Transdermal scopolamine: an alternative to ondansetron and droperidol for the prevention of postoperative and postdischarge emetic symptoms.

BACKGROUND: Given the controversy regarding the use of droperidol and the high cost of the 5-HT3 antagonists, a cost-effective alternative for routine use as a prophylactic antiemetic would be desirable. We designed two parallel, randomized, double-blind sham and placebo-controlled studies to compare the early and late antiemetic efficacy and adverse event profile of transdermal scopolamine (TDS) 1.5 mg, to ondansetron 4 mg IV, and droperidol 1.25 mg IV for antiemetic prophylaxis as part of a multimodal regimen in "at risk" surgical populations. METHODS: A total of 150 patients undergoing major laparoscopic (n = 80) or plastic (n = 70) surgery procedures received either an active TDS patch (containing scopolamine 1.5 mg) or a similar appearing sham patch 60 min before entering the operating room. All patients received a standardized general anesthetic technique. A second study medication was administered in a 2-mL numbered syringe containing either saline (for the two active TDS groups), droperidol, 1.25 mg, or ondansetron, 4 mg (for the sham patch groups), and was administered IV near the end of the procedure. The occurrence of postoperative nausea and vomiting/retching, need for rescue antiemetics, and the complete response rates (i.e., absence of protracted nausea or repeated episodes of emesis requiring antiemetic rescue medication) was reported. In addition, complaints of visual disturbances, dry mouth, drowsiness, and restlessness were noted up to 72 h after surgery. RESULTS: There were no significant differences in any of the emetic outcomes or need for rescue antiemetics among the TDS, droperidol, and ondansetron groups in the first 72 h after surgery. The complete response rates varied from 41% to 51%, and did not significantly differ among the treatment groups. The overall incidence of dry mouth was significantly more frequent in the TDS groups than in the droperidol and ondansetron groups (21% vs 3%). CONCLUSIONS: Premedication with TDS was as effective as droperidol (1.25 mg) or ondansetron (4 mg) in preventing nausea and vomiting in the early and late postoperative periods. However, the use of a TDS patch is more likely to produce a dry mouth.

Adjuvants, Anesthesia↗
PubMed2006

Meta-analysis of the safety of 5-HT3 antagonists with dexamethasone or droperidol for prevention of PONV.

BACKGROUND: Antiemetic guidelines recommend a combination of serotonin (5-HT3) with a second agent such as droperidol or dexamethasone. Physicians have been reluctant to employ these guidelines due to concerns over the black-box warning of droperidol and safety concerns with a steroid. OBJECTIVE: To assess the safety profiles of 5-HT3 receptor antagonist (5-HT3RA) monotherapy and combination therapy with a steroid or droperidol for prophylaxis of postoperative nausea and vomiting (PONV). METHODS: A MEDLINE search of English-language reports of randomized controlled trials (RCTs) was conducted (1966-September 2005) using the key terms 5-HT3, granisetron, ondansetron, dolasetron, tropisetron, PONV, postoperative, vomiting, emesis, and nausea. RCTs with treatment arms comparing 5-HT3RA monotherapy (granisetron, ondansetron, dolasetron, or tropisetron) with dexamethasone or droperidol or 5-HT3RA combinations and providing incidence data on adverse events were identified and reviewed. Within-study odds ratios with 95% confidence intervals were calculated to determine the incidence rates of all adverse events in RCTs using 5-HT3RA monotherapy and combination therapies. Overall effect sizes for frequently reported adverse events were estimated by pooling ORs using fixed- and random-effect models. RESULTS: Pooled ORs (OR(pooled)) for adverse events with 5-HT3RA/dexamethasone versus 5-HT3RA for PONV prophylaxis were not significant for any reported adverse events or the overall incidence of adverse events; 5-HT3RA/droperidol versus 5-HT3RA was significant only for decreased headache incidence (fixed model: OR(pooled) 0.35; 95% CI 0.18 to 0.69). The OR(pooled) for 5-HT3RA/dexamethasone versus dexamethasone was not significant for any reported adverse events except headaches (fixed model OR(pooled) 1.75; 95% CI 1.01 to 3.03), none of which was serious. OR(pooled) for 5-HT3RA/droperidol versus droperidol was not significant for any reported adverse events. Avascular necrosis, occult infection, and delayed wound healing were not observed with either combination therapy. Cardiac abnormalities were observed with 5-HT3RA/droperidol therapy. CONCLUSIONS: This meta-analysis indicates that either therapy has a safety profile similar to that of dexamethasone, droperidol, or 5-HT3RA.

Antiemetics↗
PubMed2004

Safety of droperidol in behavioural emergencies.

By the year 2000, droperidol had become a standard drug for the treatment of behavioural emergencies in both psychiatric and medical settings. In 2001, the US FDA issued a 'black box' warning, citing cases of QT prolongation and/or torsades de pointes. As a result, the use of droperidol has been sharply circumscribed. The authors will review the literature on antipsychotic medications in general, focusing on droperidol in particular, with regard to QT interval prolongation, dysrhythmia, and sudden death. In addition, the mechanism of drug-induced QT interval prolongation will be discussed. The authors will then review their extensive experience with droperidol. The authors conclude that, while in theory droperidol may prolong the QT interval to an extent similar to thioridazine, its long history of clinical use has shown no pattern of sudden deaths analogous to those that provoked the FDA warning. Although the numbers presented by the FDA initially appear alarming, after further evaluation it is clear that more definitive studies should have been carried out. Droperidol is safe, extremely effective, and now underused as a treatment for severely agitated or violent patients.

Adjuvants, Anesthesia↗
PubMed1975

[Action of droperidol on the ionic currents and the contraction of the sino-auricular fiber of frogs. Study of its anti-arrhythmic properties].

1. The effects of Droperidol on ionic currents were studied in frog atrial fibres by means of double sucrose-gap technique associated with an optical method for recording contraction. 2. Droperidol (5-10(-5) M) caused a significant reduction in the amplitude of the inward currents and slowed their inactivation kinetics. The decrease in the sodium and calcium current intensity may be related to the reduction in the maximum conductance for these ions. 3. A decrease in the amplitude of the first component of contractile response was shown to depend upon a reduction of the intensity of the calcium current. 4. Droperidol affected neither the potassium outward current nor the second component of the contractile response. 5. Repetitive activity induced by long-lasting depolarizing current pulses was suppressed by Droperidol. This suppression may be related to the decrease in the maximum conductance for sodium and calcium ions. 6. Droperidol increased the delay of the reactivation of the inward currents and prolonged the refractory period. 7. These results suggest that the cardiac properties of Droperidol are mainly due to a decreased conductance to Na and Ca ions.

Animals↗
PubMed2006

[Prophylactic use of droperidol for postoperative nausea and vomiting following gynecological laparoscopic surgery under total intravenous anesthesia].

BACKGROUND: Propofol and droperidol decrease the incidence of postoperative nausea and vomiting (PONV). We investigated the incidence of PONV after total intravenous anesthesia (TIVA) with propofol alone versus combined use of droperidol and propofol. METHODS: Eighty three patients, who had undergone laparoscopic gynecologic surgery with TIVA using propofol and fentanyl, were retrospectively evaluated whether droperidol had affected the incidence of early (up to six hours postoperatively) and late (6-24 hours postoperatively) PONV. Group D (46 patients) received droperidol intravenously at the end of surgery. Group N (37 patients) received no droperidol. RESULTS: The incidences of early nausea were 27% in Group N and 4% in Group D (P<0.01). The incidences of early vomiting were 0% in Group N and 8% in Group D. The incidences of late nausea were 14% in Group N and 13% in Group D. The incidences of late vomiting were 3% in Group N and 7% in Group D. CONCLUSIONS: Droperidol was useful in reducing the incidence of early nausea and vomiting after total intravenous anesthesia with propofol and fentanyl in the patients undergoing laparoscopic surgery.

Adult↗
PubMed1985

A combination of oral diazepam and droperidol for premedication. A double blind comparison with diazepam alone.

Oral diazepam is commonly used as a premedicant. For a given dose there is considerable between patient variation in clinical effect and plasma levels. The addition of droperidol may improve consistency and contribute antiemesis whilst avoiding the undesirable effects of droperidol alone. Ninety patients undergoing minor gynecological or minor urological surgery were given as an oral premedicant either diazepam (0.185 mg/kg) or one of two combinations of diazepam and droperidol (diazepam, 0.185 mg/kg plus droperidol, 0.09 mg/kg; or diazepam, 0.135 mg/kg plus droperidol, 0.09 mg/kg). There was no significant difference between the groups in altering mean anxiety measurements or improving consistency of action as judged by the number of patients having reduced anxiety measurements. Side effects, including nausea and vomiting, were not significantly different between the three groups. In the doses used there was no practical advantage in adding droperidol to diazepam for oral premedication.

Administration, Oral↗
PubMed1984

Stimulation of hypoxic ventilatory drive by droperidol.

Carotid body chemosensitivity is modulated by the neurotransmitter dopamine. Because droperidol has potent dopamine receptor blocking capability, we studied its effects on hypoxic ventilatory response. Droperidol (2.5 mg) was administered intravenously to four volunteers and their hypoxic drive was assessed by a sudden decrease in end-tidal O2 from 106 to 53 torr. End-tidal CO2 was held constant at 41 torr throughout all experiments. Droperidol caused an increase in the slope of the hypoxia-induced ventilatory response from 0.98 +/- 0.23 to 1.87 +/- 0.31 L/min per 1% decrease in saturation (mean +/- SEM, P less than 0.05). A dopamine infusion (3 micrograms X kg-1 X min-1), which depressed hypoxic drive before the administration of droperidol, did not depress the hypoxic drive after droperidol. Droperidol potentiates the hypoxic ventilatory response, presumably by blocking the action of endogenously released dopamine.

Adult↗
PubMed1982

Dissimilarities between droperidol and phentolamine on vascular tone and dopamine and norepinephrine vasoconstriction.

Droperidol has been found to have an alpha-adrenoceptor blocking potency comparable to phentolamine in in vitro studies where norepinephrine was used as the alpha agonist. Because dopamine also stimulates alpha receptors, its vasoconstrictor effects should be similarly inhibited by droperidol and phentolamine. Because the aforementioned comparisons have not been examined in vivo, we continuously infused either droperidol or phentolamine into a denervated canine hindlimb, perfused at a constant rate of blood flow, and measured changes in the basal perfusion pressure and its response to intra-arterial injections of dopamine and norepinephrine. It was found that 1) droperidol was much less potent than phentolamine in blocking the vasoconstrictor response to dopamine and norepinephrine. 2) Phentolamine's inhibition of dopamine was similar to its effect on norepinephrine whereas droperidol had the opposite effect, producing a greater inhibitory effect on norepinephrine than on dopamine. 3) The initial decrease in vascular resistance at the onset of steady state plasma levels of droperidol was quite transient while with phentolamine a corresponding decrease in vascular tone was more prolonged.

Animals↗
PubMed1995

Improving patient-controlled analgesia: adding droperidol to morphine sulfate to reduce nausea and vomiting and potentiate analgesia.

Opioid-related side effects, including nausea and vomiting, are common in patients using morphine in patient-controlled analgesia for postoperative pain relief. The purpose of this study was to determine if the addition of droperidol to a morphine sulfate delivery system could decrease the incidences of nausea and vomiting without increasing droperidol-related side effects. Forty ASA 1 and 2 patients scheduled to undergo peripheral orthopedic surgery were randomized to receive either morphine sulfate (2 mg/mL), or morphine sulfate (1.9 mg/mL) plus droperidol (0.125 mg/mL) for postoperative self-controlled analgesia. Visual analogue scores for pain, nausea, and sedation were obtained from each patient immediately after surgery and each morning and evening until patient-controlled analgesia was discontinued approximately 48 hours later. Total patient-controlled use of morphine sulfate was recorded at each visual analogue rating. The patients who used morphine sulfate plus droperidol had significantly less nausea and vomiting and used significantly less morphine. No patient experienced droperidol-related side effects. We conclude that the routine addition of droperidol to morphine sulfate in self-controlled analgesia improves the comfort of patients following peripheral orthopedic surgery.

Analgesia, Patient-Controlled↗
PubMed1995

Nitrous oxide with fentanyl and droperidol minimizes lipid peroxidation in the liver.

We have studied the level of lipid peroxidation in the liver of rats exposed to nitrous oxide plus oxygen or injected with droperidol of fentanyl. The effect of nitrous oxide used in combination with droperidol and fentanyl was also investigated. All the tested anaesthetics caused lipid peroxidation in the rat liver. It seems likely, however, that the mechanism by which droperidol and fentanyl initiate lipid peroxidation differs from that which nitrous oxide uses. Free radical products and/or activated oxygen species are produced during fentanyl and droperidol metabolism in the liver. However, nitrous oxide is not metabolized in the liver and probably undergoes one electron reduction outside the liver thus producing free radical products and/or activated oxygen species which are able to diffuse and initiate lipid peroxidation in the liver. It was also found that the level of lipid peroxidation in the liver of rats injected with droperidol and fentanyl and then exposed to nitrous oxide was low and close to that of the control animals. We suggest that, when used in combination, the products generated outside the liver as a result of nitrous oxide metabolism are transported to the liver and take part in reactions with the products of the metabolism of droperidol and fentanyl, thus decreasing the concentration of the species able to initiate lipid peroxidation.

Animals↗
PubMedDate not supplied

Droperidol interacts with vascular serotonin receptors and alpha-adrenoceptors.

This investigation was performed to determine whether droperidol interacts with 5-hydroxytryptamine (serotonin) receptors in the rat aorta. Droperidol caused concentration-dependent vasorelaxation in endothelium-intact and endothelium-denuded aortic rings precontracted with noradrenaline or 5-hydroxytryptamine. Conversely, the contractile effect of prostaglandin F2 alpha was not affected by droperidol. Pretreatment with propranolol, brompheniramine and atropine (10(-6) M each) did not alter the relaxant effects of droperidol. In addition, droperidol shifted the 5-hydroxytryptamine and noradrenaline concentration-response curves to the right in an apparently competitive manner. However, prazosin did not modify the concentration-response curve to 5-hydroxytryptamine, which is consistent with the hypothesis that the latter has an intrinsic efficacy for non-alpha 1-adrenoceptors. These results strongly suggest that a direct arterial endothelium-independent relaxant action of droperidol can be attributed to a 5-hydroxytryptamine receptor-blocking property and support its vascular alpha-adrenoceptor-blocking effect.

Animals↗
PubMed1997

Effect of low dose fentanyl-droperidol administration on respiratory drive, respiratory pattern and gas exchange in ASA 1 spontaneously breathing patients.

The aim of this study was to investigate the short term effects of low doses of fentanyl and droperidol on central respiratory drive, gas exchanges, respiratory pattern and inspiratory impedance of the respiratory system in a group of ASA 1 patients. Fourteen ASA 1 patients scheduled for minor surgery or endoscopic procedures were enrolled in the study, thirty minutes before the intervention. During spontaneous breathing of air we evaluated, by recording airflow, airway opening pressure and volume, the following variables: Respiratory Rate (RR), Tidal Volume (TV), Total respiratory cycle, Inspiratory and Expiratory Time (Ti, Te), mean inspiratory flow, P0.1, pH, PaO2 and PaCO2. After obtaining basal measurements, droperidol and fentanyl were injected and the above mentioned variables evaluated at 5 min (T1), 10 min (T2), 15 min (T3) intervals. Arterial blood was age, sampled at T3 for blood gas evaluation. The administration of droperidol (0.1 mg/kg) and fentanyl (0.002 mg/kg) significantly reduced P0.1 and Tidal Volume comparing basal with T1 and, T2 values. The other variables did not significantly modify. Two patients showed transient respiratory rhythm abnormalities in the first 180 sec following the administration of droperidol+fentanyl. Our results suggest that, in ASA 1 patients, droperidol+fentanyl preoperative administration, has no significant effects on respiratory pattern, respiratory impedance and gas exchanges: however also at low doses, the association of droperidol+fentanyl can reduce the respiratory center activity, expressed as P0.1, with a consequent reduction in Tidal Volume.

Adjuvants, Anesthesia↗
PubMed1997

Determination of a sedative dose and influence of droperidol and midazolam on cardiovascular function in pigs.

Twelve pigs were randomly assigned to 1 of 2 groups, droperidol or midazolam, to determine a sedative dose of each drug that would facilitate handling of the pigs. Each pig in the group received all of the test doses with 5-7 d between treatments (droperidol--0.1, 0.3, 0.6 mg/kg, or midazolam--0.25, 0.5, 1.0 mg/kg) and saline (3 mL), i.m. One investigator, unaware of the treatment administered, assessed the time of onset, degree, and duration of sedation. The 0.3 mg/kg dose of droperidol and 0.5 mg/kg dose of midazolam were judged to be the most suitable for sedation and produced similar degrees of sedation, although the onset and duration of sedation was significantly longer for the droperidol group. The effects of these 2 doses on heart rate, respiratory rate, systolic blood pressure, and rectal temperature were assessed in 12 pigs randomly assigned to 1 of the 2 treatments. Respiratory rate decreased significantly with droperidol at 10, 15, and 30 min. Temperature was significantly decreased at 60 min following midazolam. This study demonstrates that 0.3 mg/kg i.m. of droperidol and 0.5 mg/kg i.m. of midazolam induce adequate sedation in pigs with minimal cardiorespiratory changes.

Animals↗
PubMed1976

The magnitude and duration of respiratory depression produced by fentanyl and fentanyl plus droperidol in man.

In 10 healthy male volunteers breathing 100% oxygen, we determined the effect of four intravenous dose levels of fentanyl (0.0015, 0.003, 0.006 and 0.009 mg/kg) and two of fentanyl plus droperidol (i.e., Innovar, 0.003 and 0.006 mg/kg of fentanyl with 2.5 mg of droperidol for each 0.05 mg of fentanyl) on PECO2 and the slope of the ventilatory response to imposed increases in PECO2. All doses of fentanyl and fentanyl plus droperidol depressed the slope and shifted the curve to the right. Depression was dose related and was maximum 5 minutes after administration. The slope returned to control by 2 hours postinjection even at the highest narcotic dose. However, the rightward shift of the CO2 response curve require 4 hours to return to control. Droperidol added to fentanyl did not increase or prolong the respiratory depression seen with fentanyl alone at equivalent dose levels. Nausea and emesis occurred more frequently with fentanyl alone and orthostatic hypotension occurred more frequently with droperidol plus fentanyl. Dysphoria was a prominent consequence of fentanyl plus droperidol administration.

Adult↗
PubMedDate not supplied

Droperidol in the interim management of severe mania: case reports and literature review.

There is little information in the literature concerning the use of droperidol in psychiatry. This article presents three cases in which extremely agitated and treatment-refractory persons with mixed mania derived benefit from droperidol administered orally. Symptomatic improvement, including decreased agitation and intrusiveness, improved sleep, and decreased rates of sleep, was observed with the use of oral droperidol at doses ranging from 10-80 mg daily. The only adverse reaction was a dystonia in one patient. This article also reviews the limited available literature on the use of droperidol in psychiatry. Only eight English language articles describing the use of droperidol for psychosis or agitation were found. Future controlled studies to examine the usefulness of oral dosing of droperidol in mania are suggested.

Administration, Oral↗
PubMed1998

Epidural administration of droperidol suppresses cisplatin-induced emesis: preliminary findings.

To evaluate the antiemetic effect of the epidural administration of droperidol on cisplatin-induced emesis, nine adult gastric cancer patients receiving intraoperative cisplatin chemotherapy were studied. After removal of the stomach, 0.05 mg/kg droperidol with 5 ml saline was injected into the epidural space through the epidural catheter. Thirty minutes later, 60 mg/m2 cisplatin was administered intravenously over 1h. Subsequently, the same dose of droperidol was also injected epidurally every 6 h for 18 h. Postoperatively, the antiemetic effect was evaluated until 30 h after the first epidural droperidol. As a result, all patients expressed almost complete antiemesis until 25 h. After 26 h, some patients complained of mild emesis. No potential side effects, such as hypotension, consciousness disturbance, and extrapyramidal signs, were noticed. Therefore, the present pilot study implies that a sole epidural administration of droperidol remarkably suppresses cisplatin-induced emesis.

Adult↗
PubMed1979

Antagonism by droperidol of dopamine-induced relaxation in isolated dog arteries.

Dopamine caused a dose-related relaxation in helically cut strips of dog coronary and renal arteries treated with phenoxybenzamine andcontracted with prostaglandin F2 alpha. The dose-response curve to dopamine was shifted to the right by droperidol in concentrations above 3 X 10(-5) M. Adenosine-induced relaxations were not attenuated by droperidol. The dose--relaxation curve to isoproterenol was also shifted to the right by droperidol. Propranolol (10(-6) M) failed to significantly alter the dose response curve to dopamine, and in propranolol-treated preparations the antagonism by droperidol of dopamine actions was practically identical with that in control preparations. Droperidol appears to act as a reversible, surmountable antagonist to dopamine actions on dog arterial smooth muscles, and such evidence supports the hypothesis of specific dopamine receptors in dog arteries.

Animals↗
PubMedDate not supplied

Intravenous droperidol decreases nausea and vomiting after alfentanil anesthesia without increasing recovery time.

The frequency rate of nausea and vomiting after an alfentanil-based anesthetic is high, with reported frequencies of 38% to 68%. This study was undertaken to evaluate the efficacy of low-dose and moderate-dose droperidol in decreasing the frequency of postoperative nausea and vomiting and to evaluate whether droperidol has any effect on slowing recovery after a standard alfentanil-based anesthetic. Sixty normal adults who were scheduled to undergo short surgical procedures requiring general anesthesia were assigned randomly in a double-blind manner to one of three groups of 20: (1) control--normal saline; (2) droperidol 10 micrograms/kg; or (3) droperidol 20 micrograms/kg. A standard alfentanil-based anesthetic was used, and the study drug was given immediately after induction of anesthesia. In the post-anesthesia recovery room, all patients were evaluated according to the Aldrete score, noting the time to achieve a score of 10. Presence or absence and severity of nausea and vomiting were noted. To assess psychomotor recovery, a Trieger dot test was performed by every patient preoperatively, at the time of an Aldrete score of 10, and upon discharge from the recovery room. There was no statistical difference between the groups in age, sex, type of procedure, weight, total dose of alfentanil, or duration of anesthetic. The frequency of nausea and vomiting was significantly less (p less than 0.05) for the 20 micrograms/kg group (5%) than for the 10 micrograms/kg group (25%) or the control group (40%). A dose-response relationship was evident for the antiemetic effect of droperidol. An analog scale for severity of nausea and vomiting also demonstrated a dose response effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗