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The Cochrane Database of Systematic... Oct 2004People suffering from acute psychotic illnesses, especially those associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or... (Review)
Review
BACKGROUND
People suffering from acute psychotic illnesses, especially those associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or sedation. Droperidol, a butyrophenone neuroleptic, has been used for this purpose in several countries.
OBJECTIVES
To estimate the effects of droperidol compared to other treatments for controlling disturbed behaviour and reducing psychotic symptoms for people with suspected acute psychotic illnesses.
SEARCH STRATEGY
We updated previous searches by searching the Cochrane Schizophrenia Group Register (September 2003). References of all identified studies were searched for further trial citations and authors of trials were contacted. Twenty-one other databases were also searched as part of a broader project and this composite database was searched for this review. This was supplemented by hand searching reference lists and contacting both the pharmacological industry and relevant authors.
SELECTION CRITERIA
The review included randomised controlled trials comparing droperidol to any other treatment for people with suspected acute psychotic illnesses, including schizophrenia, schizoaffective disorder, mixed affective disorders, the manic phase of bipolar disorder or a brief psychotic episode.
DATA COLLECTION AND ANALYSIS
Relevant studies were selected for inclusion, their quality was assessed and data extracted. Data were excluded when more than 50% of participants were lost to follow up. For binary outcomes, standard estimates of risk ratio (RR) and the corresponding 95% confidence intervals (CI) were calculated. Where possible, weighted number needed to treat or harm statistics (NNT, NNH), and the corresponding 95% confidence intervals (CI), were calculated.
MAIN RESULTS
We identified only two relevant trials. One additional study focused on outcomes at 30 days rather than at a few hours. One small (n = 41) randomised trial compared intravenous (iv) droperidol (10 mg) with iv placebo and found that people allocated to droperidol were significantly less likely to need additional injections of another drug, haloperidol, in the first few minutes (n = 41, RR 0.37 CI 0.2 to 0.7, NNT 2 CI 1 to 10) compared to those given placebo. By 90 minutes this difference was still evident but not statistically significant (RR 0.46 CI 0.2 to 1.2). When 5 mg intramuscular (im) droperidol was compared with 5 mg im haloperidol, those given droperidol were also less likely to need additional injections by 30 minutes, than those given haloperidol, but this result was not statistically significant (n = 27, RR 0.45 CI 0.2 to 1.01). One person out of the 16 given haloperidol experienced a mild dystonic reaction (muscle spasms or abnormal contractions), while none of the 11 people allocated to droperidol were reported to have experienced adverse effects.
REVIEWERS' CONCLUSIONS
This is an important, and surprisingly under-researched, area. To date, use of droperidol for emergency situations has been justified by experience rather than evidence from well conducted and reported randomised trials, but, as world reserves diminish, droperidol will no longer be a treatment option.
Topics: Acute Disease; Antipsychotic Agents; Droperidol; Humans; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 15495037
DOI: 10.1002/14651858.CD002830.pub2 -
CJEM Mar 2011Butyrophenones have been reported to provide effective migraine relief in the emergency department (ED). We conducted a systematic review of the evidence for their use... (Review)
Review
OBJECTIVES
Butyrophenones have been reported to provide effective migraine relief in the emergency department (ED). We conducted a systematic review of the evidence for their use in the ED.
DATA SOURCE
We searched the Cochrane, Medline, Embase, and CINAHL databases.
STUDY SELECTION
Included studies were randomized trials of a parenteral butyrophenone (droperidol, haloperidol) versus placebo or a comparator in migraine or benign headache with results available in English. Study quality was determined using the Jadad score. Six articles were included.
DATA EXTRACTION
Primary outcomes were subjective or objective headache relief (>50% improvement in visual analogue scale scores). Secondary outcomes included side effects. We reported pooled odds ratios (ORs) with their 95% confidence intervals (CIs) for subjective or objective headache relief for butyrophenones versus placebo or comparator agents.
DATA SYNTHESIS
Three studies reported subjective headache relief with a butyrophenone versus placebo or meperidine in migraine. Two studies reported objective headache relief with droperidol versus prochlorperazine, whereas one study compared droperidol versus olanzapine in benign headache. The pooled OR for subjective headache relief was 8.08 (95% CI 1.54-42.30) for a butyrophenone versus placebo, whereas it was 1.50 (95% CI 0.33-6.77) for droperidol versus meperidine in migraine. The pooled OR for objective headache relief was 2.96 (95% CI 1.36-6.43) for droperidol versus prochlorperazine in benign headache. Rates of side effects were 10 to 45%; akathesia and sedation were the most common.
CONCLUSIONS
Butyrophenones are effective for the relief of migraine or benign headache. However, adverse effects make it difficult to recommend butyrophenones above agents with similar effectiveness and fewer problems.
Topics: Butyrophenones; Droperidol; Emergency Service, Hospital; Haloperidol; Headache; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 21435315
DOI: 10.2310/8000.2011.100301 -
Anaesthesia Oct 2012The population sampling in randomised controlled trials by Fujii et al. have been shown to exhibit unusual distributions. This systematic review analysed the... (Meta-Analysis)
Meta-Analysis Review
The population sampling in randomised controlled trials by Fujii et al. have been shown to exhibit unusual distributions. This systematic review analysed the effectiveness of prophylactic antiemetics in trials by Fujii et al. compared with other authors. Granisetron was more effective in trials by Fujii et al., relative risk ratios (RRR (95% CI)): nausea 0.53 (0.42-0.67), p=0.00021; vomiting 0.60 (0.50-0.73), p=0.00094. Ramosetron was also more effective in studies by Fujii et al.: vomiting 0.60 (0.39-0.91), p=0.02; nausea or vomiting 0.71 (0.56-0.91); p=0.006. In comparison with granisetron, droperidol was less effective in trials by Fujii et al. than others: nausea 2.41 (1.72-3.36), p=2.5×10(-7); vomiting 1.73 (1.26-2.38), p=6.4×10(-4). Postoperative nausea and vomiting was less likely to trigger rescue antiemesis after granisetron and metoclopramide in studies by Fujii et al., 0.40 (0.27-0.60), p=9.7×10(-6). Triggered rates of rescue were not different in studies by others for droperidol, granisetron and metoclopramide, but were less common after granisetron than droperidol and metoclopramide in studies by Fujii et al., 0.50 (0.38-0.66), p=1.7×10(-6) and 0.47 (0.34-0.64), p=2.6×10(-6), respectively. There was no synergism between antiemetics in trials by other authors. In contrast, in studies by Fujii et al., postoperative nausea and vomiting was more likely if granisetron was administered alone: nausea 4.20 (1.94-9.08), p=2.6×10(-4) ; vomiting 4.50 (2.55-7.97), p=2.3×10(-7); nausea or vomiting 5.00 (2.84-8.81), p=2.5×10(-8). Similarly, droperidol was less effective in studies by Fujii et al. if administered alone: vomiting 2.76 (1.25-6.11), p=0.01; nausea or vomiting 2.96 (1.46-6.00), p=2.7×10(-3). The conclusion is that if, as recommended, data with unusual distributions are removed from meta-analysis and articles by Fujii et al. excluded, then the antiemetic effects of granisetron and ramosetron are greatly reduced; further, there is no evidence of synergism between antiemetics and indeed, some evidence of antagonism between antiemetic agents.
Topics: Antiemetics; Benzimidazoles; Data Interpretation, Statistical; Droperidol; Drug Interactions; Drug Therapy, Combination; Granisetron; Humans; Meta-Analysis as Topic; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome
PubMed: 22734848
DOI: 10.1111/j.1365-2044.2012.07232.x -
British Journal of Anaesthesia Nov 1995Randomized controlled studies were reviewed to assess the effectiveness and safety of antiemetics used for prophylaxis in paediatric strabismus surgery. Early and late... (Review)
Review
Randomized controlled studies were reviewed to assess the effectiveness and safety of antiemetics used for prophylaxis in paediatric strabismus surgery. Early and late vomiting (6 and 48 h after operation, respectively), and adverse effects were evaluated using the numbers-needed-to-treat method. In 27 reports with information on 2033 children, the mean incidence of early vomiting was 54% and of late vomiting 59%, without prophylaxis. Only three drugs were studied sufficiently for firm conclusions to be drawn. In the best documented regimen (droperidol 75 micrograms kg-1), four children have to be given the drug to prevent one vomiting; of the three others, one may vomit and two would not have vomited anyway; fewer than one child in 100 may have an extrapyramidal reaction and 16 may have minor adverse effects. Metoclopramide 0.15 and 0.25 mg kg-1 was significantly better than control only for early vomiting. Propofol had a high incidence of oculocardiac reflex without conferring any significant antiemetic effect: it should not be used. The benefits of prophylactic antiemetic therapy are not proven.
Topics: Antiemetics; Child; Droperidol; Humans; Postoperative Complications; Propofol; Randomized Controlled Trials as Topic; Strabismus; Vomiting
PubMed: 7577280
DOI: 10.1093/bja/75.5.556 -
Journal of Evidence-based Medicine Sep 2021In this abridged version of the recently published Cochrane review on antiemetic drugs, we summarize its most important findings and discuss the challenges and the time... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
In this abridged version of the recently published Cochrane review on antiemetic drugs, we summarize its most important findings and discuss the challenges and the time needed to prepare what is now the largest Cochrane review with network meta-analysis in terms of the number of included studies and pages in its full printed form.
METHODS
We conducted a systematic review with network meta-analyses to compare and rank single antiemetic drugs and their combinations belonging to 5HT₃-, D₂-, NK₁-receptor antagonists, corticosteroids, antihistamines, and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anesthesia.
RESULTS
585 studies (97 516 participants) testing 44 single drugs and 51 drug combinations were included. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 studies, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared to placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single NK receptor antagonists were as effective as other drug combinations. Of the 10 effective single drugs, certainty of evidence was high for aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron, while moderate for fosaprepitant and droperidol. For serious adverse events (SAEs), any adverse event (AE), and drug-class specific side effects evidence for intervention effects was mostly not convincing.
CONCLUSIONS
There is high or moderate evidence for at least seven single drugs preventing postoperative vomiting. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.
Topics: Adult; Anesthesia, General; Antiemetics; Humans; Network Meta-Analysis; Pharmaceutical Preparations; Postoperative Nausea and Vomiting
PubMed: 34043870
DOI: 10.1111/jebm.12429 -
Basic & Clinical Pharmacology &... Jan 2021Opioid poisoning is a frequent cause of death in drug addicts and occurs with opioid treatment. Quetiapine is often found in forensic autopsies and may increase the risk...
Opioid poisoning is a frequent cause of death in drug addicts and occurs with opioid treatment. Quetiapine is often found in forensic autopsies and may increase the risk of fatal opioid poisoning by enhancing sedation, respiratory depression, hypotension and QT prolongation. We systematically searched for studies of acute toxicity of quetiapine or other antipsychotics combined with morphine or methadone. Case reports describing toxicity of quetiapine combined with morphine or methadone were also included. We retrieved one human study that observed pharmacokinetic interaction between quetiapine and methadone, and 16 other human studies. Fourteen investigated the combination of droperidol and morphine in treatment doses, and some indicated an additive sedative effect. Five animal studies with acepromazine in combination with morphine or methadone were located and indicated an additive effect on sedation and hypotension. Six forensic case reports in which death could have been caused solely by quetiapine, the opioid, or other drugs were found. Thus, acute toxicity of quetiapine combined with morphine or methadone has not been studied. Because of quetiapine's effects on alpha-adrenoceptors, muscarinic and histamine receptors, human ether-a-go-go-channels and methadone kinetics, we suggest further research to clarify if the indicated additive effects of opioids and droperidol or acepromazine are also true for quetiapine.
Topics: Adolescent; Adult; Analgesics, Opioid; Animals; Antipsychotic Agents; Arrhythmias, Cardiac; Autopsy; Cause of Death; Consciousness; Drug Interactions; Drug Overdose; Female; Forensic Toxicology; Humans; Hypotension; Male; Methadone; Middle Aged; Morphine; Opioid-Related Disorders; Quetiapine Fumarate; Respiratory Insufficiency; Risk Assessment; Risk Factors
PubMed: 33245632
DOI: 10.1111/bcpt.13480 -
The Cochrane Database of Systematic... Sep 2012Nausea and vomiting are distressing symptoms which are experienced commonly during caesarean section under regional anaesthesia and can also occur in the period... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nausea and vomiting are distressing symptoms which are experienced commonly during caesarean section under regional anaesthesia and can also occur in the period following the procedure.
OBJECTIVES
To assess the efficacy of pharmacological and non-pharmacological interventions given prophylactically to prevent nausea and vomiting in women undergoing regional anaesthesia for caesarean section.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (27 February 2012) and reference lists of identified studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and excluded quasi-RCTs and cross-over studies.
DATA COLLECTION AND ANALYSIS
Review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked.
MAIN RESULTS
Fifty-two studies met the inclusion criteria but only 41 studies, involving 5046 women, provided useable data for the review involving women having caesareans under regional anaesthesia. The majority of the studies involved women undergoing elective caesarean section. Only two studies included emergency surgery, however, they did not stratify data according to type of surgery. The studies covered numerous comparisons, but the majority of studies involved 5-HT(3) receptor antagonists, dopamine receptor antagonists, corticosteroids or acupressure. Studies were mainly small and of unclear quality.Three classes of intervention were found to be effective in at least three out of four of our primary outcomes (intraoperative nausea, intraoperative vomiting, postoperative nausea and postoperative vomiting). These interventions were 5-HT(3) antagonists, dopamine antagonists and sedatives. Other classes of intervention were effective for fewer than three of our primary outcomes.With 5-HT antagonists, we found a reduction in intraoperative nausea (average risk ratio (RR) 0.64, 95% confidence interval (CI) 0.46 to 0.88, eight studies, 720 women). There were also reductions in postoperative nausea (average RR 0.40, 95% CI 0.25 to 0.64, four studies, 405 women) and vomiting (average RR 0.50, 95% CI 0.32 to 0.77, five studies, 565 women). We did not detect a significant reduction in intraoperative vomiting (average RR 0.56, 95% CI 0.31 to 1.00, seven studies, 668 women).Dopamine antagonists demonstrated a reduction in intraoperative nausea (average RR 0.38, 95% CI 0.25 to 0.57, nine studies, 636 women) and intraoperative vomiting (average 0.39, 95% CI 0.24 to 0.64, eight studies, 536 women), with similar reductions in postoperative nausea (average RR 0.60, 95% CI 0.40 to 0.91, five studies, 412 women) and vomiting (average RR 0.57, 95% CI 0.36 to 0.91, six studies, 472 women). These differences were observed with both metoclopramide and droperidol.Sedatives (most commonly propofol) demonstrated a reduction in intraoperative nausea (average RR 0.71, 95% CI 0.52 to 0.96, four studies, 285 women) and intraoperative vomiting (average RR 0.42, 95% CI 0.26 to 0.68, four studies, 285 women), also with a reduction in postoperative nausea (average RR 0.25, 95% CI 0.09 to 0.71, two studies 145 women) and vomiting (average RR 0.09, 95% CI 0.03 to 0.28, two studies, 145 women).Acupressure was found to be effective for intraoperative nausea (average RR 0.59, 95% CI 0.38 to 0.90, six studies, 649 women) but not postoperative nausea (average RR 0.83, 95% CI 0.68 to 1.00, three studies, 429 women). Acupressure was not effective at reducing vomiting either intraoperatively (average RR 0.74, 95% CI 0.46 to 1.18, six studies, 649 women) or postoperatively (average RR 0.69, 95% CI 0.45 to 1.06, three studies, 429 women).Other effective intervention classes included corticosteroids, antihistamines, and anticholinergics.There were insufficient data to demonstrate any class of intervention was superior to another. There were no significant differences observed in the comparison of combined versus single interventions.Few studies assessed our secondary outcomes or the incidence of adverse effects. However, one study showed an increase in respiratory depression with sedation (midazolam) compared with dopamine antagonists.
AUTHORS' CONCLUSIONS
This review indicates that many different interventions have efficacy in preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section. There is little evidence that combinations of treatment are better than single agents.
Topics: Acupressure; Adrenal Cortex Hormones; Anesthesia, Conduction; Cesarean Section; Dopamine Antagonists; Female; Humans; Hypnotics and Sedatives; Intraoperative Complications; Nausea; Postoperative Nausea and Vomiting; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Serotonin Antagonists; Vomiting
PubMed: 22972112
DOI: 10.1002/14651858.CD007579.pub2 -
The Annals of Pharmacotherapy Nov 2006To determine which antipsychotic is associated with the greatest efficacy and safety when used for the pharmacotherapeutic management of delirium in medically or... (Comparative Study)
Comparative Study Review
OBJECTIVE
To determine which antipsychotic is associated with the greatest efficacy and safety when used for the pharmacotherapeutic management of delirium in medically or surgically ill patients.
DATA SOURCES
MEDLINE, Current Contents, Cumulative Index of Nursing and Allied Health Literature, PsycINFO, Biological Abstracts, Cochrane Central Register of Controlled Trials, and EMBASE databases (all to July 2006) were searched for trials evaluating the pharmacologic treatment of delirium in medically or surgically ill patients. The key terms used included delirium, agitation, or acute confusion, and antipsychotics, phenothiazine, butyrophenone, perphenazine, fluphenazine, clozapine, trifluorophenazine, loxapine, thioridazine, pimozide, molindone, haloperidol, methotrimeprazine, chlorpromazine, prochlorperazine, droperidol, risperidone, quetiapine, ziprasidone, amisulpride, or olanzapine.
STUDY SELECTION AND DATA EXTRACTION
Prospective, randomized, controlled trials comparing the clinical effects of antipsychotic therapy with placebo or comparing 2 antipsychotic treatments in an acute care setting were selected. Studies involving dementia-associated delirium, Alzheimer's disease-associated delirium, emergency department-associated acute agitation, acute brain trauma-associated agitation, or agitation secondary to underlying psychiatric afflictions such as depression or schizophrenia were excluded. All studies were evaluated independently by the 3 authors using a validated evaluation tool. Outcomes related to both efficacy and safety were collected. Four prospective trials were included in this systematic review.
DATA SYNTHESIS
Antipsychotic agents, either atypical or typical, were effective compared with baseline for the treatment of delirium in medically or surgically ill patients without underlying cognitive disorders. Oral haloperidol was associated with more frequent extrapyramidal side effects, but overall, all agents were well tolerated. Interpretation of the published evidence is limited by the small sample sizes, varied patient populations, and comparative agents of the studies reviewed.
CONCLUSIONS
The comparative studies evaluated here suggest that antipsychotic drugs are efficacious, when compared with baseline, and safe for the treatment of delirium. Haloperidol remains the most studied agent. Recommendation of one antipsychotic over another as a first-line pharmacologic intervention in the treatment of hospital-associated delirium is limited by the quality and quantity of data available. Better designed and larger studies evaluating the addition of antipsychotic agents to nonpharmacologic treatments are needed to measure the true effect of pharmacologic treatment.
Topics: Antipsychotic Agents; Delirium; Haloperidol; Hospital Departments; Hospitalization; Humans; Surgery Department, Hospital
PubMed: 17047137
DOI: 10.1345/aph.1H241 -
International Journal of Mental Health... Apr 2020One approach to manage people with behaviours of concern including agitated or aggressive behaviours in health care settings is through the use of fast-acting...
One approach to manage people with behaviours of concern including agitated or aggressive behaviours in health care settings is through the use of fast-acting medication, called chemical restraint. Such management often needs to be delivered in crisis situations to patients who are at risk of harm to themselves or others. This paper summarizes the available evidence on the effectiveness and safety of chemical restraint from 21 randomized controlled trials (RCTs) involving 3788 patients. The RCTs were of moderate to high quality and were conducted in pre-hospital, hospital emergency department, or ward settings. Drugs used in chemical restraint included olanzapine, haloperidol, droperidol, risperidol, flunitrazepam, midazolam, promethazine, ziprasidone, sodium valproate, or lorazepam. There was limited comparability between studies in drug choice, combination, dose, method of administration (oral, intramuscular, or intravenous drip), or timing of repeat administrations. There were 31 outcome measures, which were inconsistently reported. They included subjective measures of behaviours, direct measures of treatment effect (time to calm; time to sleep), indirect measures of agitation (staff or patient injuries, duration of agitative or aggressive episodes, subsequent violent episodes), and adverse events. The most common were time to calm and adverse events. There was little clarity about the superiority of any chemical method of managing behaviours of concern exhibited by patients in Emergency Departments or acute mental health settings. Not only is more targeted research essential, but best practice recommendations for such situations requires integrating expert input into the current evidence base.
Topics: Aggression; Conscious Sedation; Humans; Hypnotics and Sedatives; Psychomotor Agitation; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31498960
DOI: 10.1111/inm.12654 -
Anesthesia and Analgesia Jun 1999Nausea and vomiting are frequent adverse effects of patient-controlled analgesia (PCA) with opioids. To identify the optimal prophylactic antiemetic intervention in this... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Nausea and vomiting are frequent adverse effects of patient-controlled analgesia (PCA) with opioids. To identify the optimal prophylactic antiemetic intervention in this setting, we performed a systematic search for randomized trials (MEDLINE, EMBASE, Cochrane library, reference lists, hand-searching, no language restriction) published up to May 1998 that compared prophylactic antiemetic interventions with placebo or no treatment in the postoperative PCA-setting with opioids. Fourteen placebo-controlled trials (1117 patients) with different regimens of droperidol, ondansetron, hyoscine TTS, tropisetron, metoclopramide, propofol, and promethazine were analyzed. One PCA was with tramadol, all others were with morphine. At 24 h, the cumulative incidence of nausea and vomiting without antiemetics was approximately 50%. Droperidol 0.017-0.17 mg/mg of morphine (0.5-11 mg/d droperidol) was statistically significantly more effective than placebo without evidence of dose-responsiveness; the number needed to treat to prevent nausea compared with placebo was 2.7 (95% confidence interval 1.8-5.2), and that to prevent vomiting was 3.1 (2.3-4.8). Compared with placebo, the incidence of minor adverse effects with droperidol was increased with doses >4 mg/d.
IMPLICATIONS
Of 100 patients treated with droperidol added in a patient-controlled analgesia pump with morphine, 30 who would have vomited or been nauseated had they not received droperidol will not suffer these effects. There is no evidence of dose-responsiveness for efficacy with droperidol, but the risk of adverse effects is dose-dependent. There is a lack of evidence for other antiemetics.
Topics: Analgesia, Patient-Controlled; Analgesics, Opioid; Antiemetics; Droperidol; Humans; Morphine; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 10357345
DOI: 10.1097/00000539-199906000-00030