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Journal of the Academy of... 2024Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available... (Review)
Review
Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies.
Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available management options include de-escalation techniques and rapid tranquilization, mostly via parenteral formulations of medication. While the intramuscular route has been extensively studied in a range of clinical settings, the same cannot be said for intravenous (IV); this is despite potential benefits, including rapid absorption and complete bioavailability. This systematic review analyzed existing evidence for effectiveness and safety of IV medication for management of acute disturbances. It followed a preregistered protocol (PROSPERO identification CRD42020216456) and is reported following the guidelines set by Preferred Reporting Items for Systematic Review and Meta-Analysis. APA PsycINFO, MEDLINE, and EMBASE databases were searched for eligible interventional studies up until May 30th, 2023. Data analysis was limited to narrative synthesis since primary outcome measures varied significantly. Results showed mixed but positive results for the effectiveness of IV dexmedetomidine, lorazepam, droperidol, and olanzapine. Evidence was more limited for IV haloperidol, ketamine, midazolam, chlorpromazine, and valproate. There was no eligible data on the use of IV clonazepam, clonidine, diazepam, diphenhydramine, propranolol, ziprasidone, fluphenazine, carbamazepine, or promethazine. Most studies reported favorable adverse event profiles, though they are unlikely to have been sufficiently powered to pick up rare serious events. In most cases, evidence was of low or mixed quality, accentuating the need for further standardized, large-scale, multi-arm randomized controlled trials with homogeneous outcome measures. Overall, this review suggests that IV medications may offer an effective alternative parenteral route of administration in acute disturbance, particularly in general hospital settings.
Topics: Humans; Administration, Intravenous; Psychomotor Agitation; Aggression; Antipsychotic Agents; Prospective Studies
PubMed: 38309683
DOI: 10.1016/j.jaclp.2024.01.004 -
Australasian Emergency Care Jun 2021Chemical restraint (CR) is emergency drug management for acute behavioural disturbances in people with mental illness, provided with the aim of rapid calming and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chemical restraint (CR) is emergency drug management for acute behavioural disturbances in people with mental illness, provided with the aim of rapid calming and de-escalating potentially dangerous situations.
AIMS
To describe a systematic review of Randomised Controlled Trials (RCTs) reporting on short-term safety and effectiveness of drugs used for CR, administered to non-consenting adults with mental health conditions, who require emergency management of acute behavioural disturbances. A meta-analysis was conducted of those RCTs with comparable interventions, outcome measures and measurement timeframes.
METHOD
Academic databases were searched for RCTs published between 1 January 1996 and 20th April 2020. Relevant RCTs were critically appraised using the 13-item JBI checklist. All RCTs were described, and step-wise filters were applied to identify studies suitable for meta-analysis. For these, forest and funnel plots were constructed, and Q and I statistics guided interpretation of pooled findings, tested using MedCalc Version 19.1.
RESULTS
Of 23 relevant RCTs, 18 (78.2% total) had excellent methodological quality scores (at least 90%). Eight RCTs were potentially relevant for meta-analysis (six of excellent quality), reporting 20 drug arms in total. Adverse events for 6-36% patients were reported in all 20 drug arms. Four drug arms from two homogenous studies of N = 697 people were meta-analysed. These RCTs tested two antipsychotic drugs (droperidol, olanzapine) delivered intravenously in either 5 mgs or 10 mg doses, with outcomes of time to calm, percentage calm within five or 10 min, and adverse events. There were no significant differences between drug arms for either measure of calm. However, 5 mg olanzapine incurred significantly lower risk of adverse events than 10 mg olanzapine (OR 0.4 (95%CI 0.2-0.8)), although no dose differences were found for droperidol.
CONCLUSION
5 mg intravenous olanzapine is recommended for quick, safe emergency management of people with acute behavioural disturbances associated with mental illness.
Topics: Antipsychotic Agents; Droperidol; Humans; Olanzapine; Tranquilizing Agents
PubMed: 33046432
DOI: 10.1016/j.auec.2020.08.004 -
Academic Emergency Medicine : Official... Dec 2022Agitation in children in acute care settings poses significant patient and staff safety concerns. While behavioral approaches are central to reducing agitation and oral... (Review)
Review
OBJECTIVE
Agitation in children in acute care settings poses significant patient and staff safety concerns. While behavioral approaches are central to reducing agitation and oral medications are preferred, parenteral medications are used when necessary to promote safety. The goal of this systematic review was to evaluate the effectiveness and safety of an ultra-short-acting parenteral medication, droperidol, for the management of acute, severe agitation in children in acute care settings.
METHODS
A systematic review of randomized controlled trials, observational studies, and case series/reports examined the effectiveness and safety of parenteral droperidol for management of acute agitation in patients ≤21 years old in acute care settings. Effectiveness outcomes included time to sedation and need for a subsequent dose of medication. Safety outcomes were adverse effects such as QTc prolongation, hypotension, respiratory depression, and dystonic reactions.
RESULTS
A total of 431 unique articles were identified. Six articles met inclusion criteria: two in the prehospital setting, one in the emergency department, and three in the inpatient hospital setting. The articles included a prospective observational study, three retrospective observational studies, and two case reports. The largest study reported a median time to sedation of 14 min (interquartile range 10-20 min); other studies reported a time to sedation of 15 min or less. Across studies, 8%-22% of patients required a second dose of medication for ongoing agitation. The most frequent adverse effects were dystonic reactions and transient hypotension. One patient had QTc prolongation and another developed respiratory depression, but both had significant comorbidities that may have contributed. The risk of bias in included studies ranged from moderate to critical.
CONCLUSIONS
Existing data on droperidol for management of acute agitation in children suggest that droperidol is both effective and safe for acute, severe agitation in children. Data are limited by study designs that may introduce bias.
Topics: Humans; Child; Young Adult; Adult; Droperidol; Retrospective Studies; Emergency Service, Hospital; Prospective Studies; Respiratory Insufficiency; Psychomotor Agitation; Observational Studies as Topic
PubMed: 35490341
DOI: 10.1111/acem.14515 -
International Journal of Surgery... Sep 2019Different categories of drugs are used to reduce the incidence of post-operative nausea and vomiting (PONV) following laparoscopic cholecystectomy (LC). This study is a... (Review)
Review
Drugs for preventing post-operative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: Network meta-analysis of randomized clinical trials and trial sequential analysis.
BACKGROUND
Different categories of drugs are used to reduce the incidence of post-operative nausea and vomiting (PONV) following laparoscopic cholecystectomy (LC). This study is a network meta-analysis of randomized clinical trials with such drugs.
METHODS
Electronic databases were searched for appropriate randomized clinical trials evaluating drugs reducing PONV in LC. Number of patients without PONV at 24 h was the primary outcome; and incidence of nausea and/or vomiting at 6 h and 24 h, and adverse events were the secondary outcome measures. Risk of bias was evaluated for each study. Mixed treatment comparison estimates were derived by random-effects modelling. Trial sequential analysis was carried out to assess the adequacy of evidence; and surface area under cumulative ranking curve was generated to identify the best intervention in the pool. Grading of the evidence for key comparisons was done.
RESULTS
Ninety clinical trials were included. Metoclopramide, gabapentin, dixyrazine, ondansetron, granisetron, dexamethasone, tropisetron, droperidol, droperidol/dexamethasone, droperidol/metoclopramide, granisetron/droperidol and granisetron/dexamethasone, haloperidol, dexmedetomidine, palonosetron, droperidol/ondansetron, metoclopramide/dexamethasone, haloperidol/ondansetron, haloperidol/dexamethasone, palonosetron/dexamethasone and ramosetron/dexamethasone were observed with significant benefits compared to placebo. Corticosteroid/serotonin receptor antagonists was observed with the highest probability of being the 'best' in this pool. However, the moderate quality of evidence obtained was adequate to confirm the benefits of dexamethasone and ondansetron only.
CONCLUSION
The relative effect sizes for various prophylactic anti-emetics for LC was modelled using the principles of network meta-analysis. Dexamethasone and ondansetron have the best evidence as stand-alone options and the combination is preferred in high-risk category. Caution should be exercised while interpreting the evidence as the estimates might change with head-to-head clinical trial data.
Topics: Antiemetics; Cholecystectomy, Laparoscopic; Dexamethasone; Drug Therapy, Combination; Humans; Network Meta-Analysis; Ondansetron; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic
PubMed: 31299429
DOI: 10.1016/j.ijsu.2019.07.002 -
The Medical Letter on Drugs and... Dec 2022
Topics: Humans; Dexmedetomidine; Antipsychotic Agents; Benzodiazepines; Psychomotor Agitation
PubMed: 36542347
DOI: No ID Found -
Addiction (Abingdon, England) Jul 2017To examine the efficacy and safety of (1) midazolam-droperidol versus droperidol and (2) midazolam-droperidol versus olanzapine for methamphetamine-related acute... (Randomized Controlled Trial)
Randomized Controlled Trial
Intravenous midazolam-droperidol combination, droperidol or olanzapine monotherapy for methamphetamine-related acute agitation: subgroup analysis of a randomized controlled trial.
AIM
To examine the efficacy and safety of (1) midazolam-droperidol versus droperidol and (2) midazolam-droperidol versus olanzapine for methamphetamine-related acute agitation.
DESIGN AND SETTING
A multi-centre, randomized, double-blind, controlled, clinical trial was conducted in two Australian emergency departments, between October 2014 and September 2015.
PARTICIPANTS
Three hundred and sixty-one patients, aged 18-65 years, requiring intravenous medication sedation for acute agitation, were enrolled into this study. We report the results of a subgroup of 92 methamphetamine-affected patients.
INTERVENTION AND COMPARATOR
Patients were assigned randomly to receive either an intravenous bolus of midazolam 5 mg-droperidol 5 mg combined, droperidol 10 mg or olanzapine 10 mg. Two additional doses were administered, if required: midazolam 5 mg, droperidol 5 mg or olanzapine 5 mg, respectively.
MEASUREMENTS
The primary outcome was the proportion of patients sedated adequately at 10 minutes. Odds ratios with 95% confidence intervals (ORs, 95% CI) were estimated.
FINDINGS
The baseline characteristics of patients in the three groups were similar. At 10 minutes, significantly more patients in the midazolam-droperidol group [29 of 34 (85.3%)] were sedated adequately compared with the droperidol group [14 of 30 (46.7%), OR = 6.63, 95% CI = 2.02-21.78] or with the olanzapine group [14 of 28 (50.0%), OR 5.80, 95% CI = 1.74-19.33]. The number of patients who experienced an adverse event (AE) in the midazolam-droperidol, droperidol and olanzapine groups was seven of 34, two of 30 and six of 28, respectively. The most common AE was oxygen desaturation.
CONCLUSION
A midazolam-droperidol combination appears to provide more rapid sedation of patients with methamphetamine-related acute agitation than droperidol or olanzapine alone.
Topics: Acute Disease; Adolescent; Adult; Aged; Akathisia, Drug-Induced; Australia; Benzodiazepines; Dopamine D2 Receptor Antagonists; Double-Blind Method; Droperidol; Drug Therapy, Combination; Female; Humans; Hypnotics and Sedatives; Injections, Intravenous; Male; Methamphetamine; Midazolam; Middle Aged; Olanzapine; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Young Adult
PubMed: 28160494
DOI: 10.1111/add.13780 -
Fujita Medical Journal 2019This study aimed to evaluate the effect of preventive administration of the combination of droperidol and dexamethasone on lowering the risk for postoperative nausea and...
Clinical evaluation of postoperative nausea and vomiting after cleft lip and/or palate surgery in pediatric patients. Part 2: evaluation of preventive administration of droperidol in combination with dexamethasone.
OBJECTIVES
This study aimed to evaluate the effect of preventive administration of the combination of droperidol and dexamethasone on lowering the risk for postoperative nausea and vomiting (PONV) after cleft-related surgery in pediatric patients.
METHODS
Preventive care consisted of a single dose of droperidol (0.025 mg/kg) and dexamethasone (0.06 mg/kg), which were administered at the end of surgery. The effect of preventive administration was evaluated in a sample group of 58 patients aged ≥3 years who underwent cleft-related surgery. Thirty patients received preventive administration (prevention group) and 28 patients did not (comparative group). The following outcome variables were evaluated between the groups: sex, age, body weight at the time of surgery, and duration of anesthesia. The presence or absence of PONV was the primary outcome and other variables were considered as explanatory variables.
RESULTS
The incidence rate of PONV was 20% (6/30) in the prevention group and 28.6% (8/28) in the comparative group, with no significant difference between the groups (p=0.45). In multiple logistic regression analysis, sex was the only explanatory factor of PONV, with a higher risk in girls than in boys (odds ratio, 6.20; 95% confidence interval, 1.65-27.63; p=0.01).
CONCLUSIONS
The incidence rate of PONV is 20% with preventive care of droperidol and dexamethasone administration, but this rate is not different from that without this combination. Sex is a risk factor for PONV. Further studies are required to validate our results.
PubMed: 35111502
DOI: 10.20407/fmj.2018-008 -
Reproductive Toxicology (Elmsford, N.Y.) Aug 2019Nausea and vomiting of pregnancy (NVP) is the most common medical complaint during pregnancy affecting up to 70% of pregnant women worldwide. Some antiemetic medications...
Nausea and vomiting of pregnancy (NVP) is the most common medical complaint during pregnancy affecting up to 70% of pregnant women worldwide. Some antiemetic medications (AEM) (droperidol, domperidone, granisetron, metoclopramide and trifluoperazine) used to treat NVP have the unwanted side effect of hERG blockade. The hERG potassium channel is essential for normal heart rhythm in both the adult human and the human and rat embryo. Animal studies show hERG blockade in the embryo causes bradycardia and arrhythmia leading to cardiovascular malformations and other birth defects. Whole rat embryo in vitro culture was used to determine the effect of the above listed AEM and meclizine on the heart rate of Gestational day 13 rat embryos. These embryos are similar in size and heart development to 5-6-week human embryo. The results showed that all of the AEMs caused a concentration-dependent bradycardia. Droperidol had the lowest margin of safety.
Topics: Animals; Antiemetics; Bradycardia; Domperidone; Droperidol; Embryo, Mammalian; Granisetron; Heart; Heart Rate; Meclizine; Metoclopramide; Rats, Sprague-Dawley; Trifluoperazine
PubMed: 31199962
DOI: 10.1016/j.reprotox.2019.06.002 -
PharmacoEconomics - Open Jun 2018The combination of midazolam and droperidol has proven superior to droperidol or olanzapine monotherapy in the management of acute agitation in emergency departments...
Economic Evaluation of Midazolam-Droperidol Combination, Versus Droperidol or Olanzapine for the Management of Acute Agitation in the Emergency Department: A Within-Trial Analysis.
BACKGROUND
The combination of midazolam and droperidol has proven superior to droperidol or olanzapine monotherapy in the management of acute agitation in emergency departments (EDs).
OBJECTIVE
This is the first economic analysis to evaluate the cost-benefit and cost effectiveness of the midazolam-droperidol combination compared with droperidol or olanzapine for the management of acute agitation in EDs.
METHODS
This analysis used data derived from a randomised, controlled, double-blind clinical trial conducted in two metropolitan Australian EDs between October 2014 and August 2015. The economic evaluation was from the perspective of Australian public hospital EDs. The main outcomes included agitation management time and the agitation-free time gained. Sensitivity analyses were undertaken.
RESULTS
The midazolam-droperidol combination was the least costly regimen (Australian dollars [AU$]46.25 per patient) compared with the droperidol and olanzapine groups (AU$92.18 and AU$110.45 per patient, respectively). The main cost driver for all groups was the cost of the labour required during the initial adequate sedation. The combination afforded an additional 10-13 min of mean agitation-free time gained, which can be translated to additional savings of AU$31.24-42.60 per patient compared with the droperidol and olanzapine groups. The benefit-cost ratio for the midazolam-droperidol combination was 12.2:1.0, or AU$122,000 in total benefit for every AU$10,000 spent on management of acute agitation. Sensitivity analyses over key variables indicated these results were robust.
CONCLUSIONS
The midazolam-droperidol combination may be a cost-saving and dominant cost-effective regimen for the treatment of acute agitation in EDs as it is more effective and less costly than either droperidol or olanzapine monotherapy.
PubMed: 29623620
DOI: 10.1007/s41669-017-0047-y -
European Journal of Clinical... May 2021Most psychiatric drugs, such as antidepressants (AD) and antipsychotics (AP), may cause cardiac adverse events (CAE). We used summaries of product characteristics (SmPC)...
PURPOSE
Most psychiatric drugs, such as antidepressants (AD) and antipsychotics (AP), may cause cardiac adverse events (CAE). We used summaries of product characteristics (SmPC) for assessing the likelihood of AD and AP to cause CAE.
METHODS
We identified all original medicinal products (OMP) of AD and AP approved in Germany. We searched for their SmPCs using the online services of PharmaNet.Bund, Gelbe liste®, Rote Liste®, Fachinfo-Service®, and via manufacturer contact. We extracted frequencies of reported CAE (QT prolongation, Torsade de Pointes tachycardia, and ventricular arrhythmia) and performed a risk assessment.
RESULTS
We obtained the SmPCs of 24 AD and 26 AP identified as OMP. Comparably high reported frequencies regarding QT prolongation were found for Invega® (paliperidone), Serdolect® (sertindole) (≥ 1/100 and < 1/10), and Zoloft® (sertraline) (≥ 1/10.000 and < 1/1000); regarding Torsade de Pointes tachycardia were found for Serdolect® (≥ 1/1000 to < 1/100), Zoloft®, and Trevilor® (venlafaxine) (≥ 1/10.000 and < 1/1000); regarding ventricular tachycardia for Solian® (amisulpride), Xomolix® (droperidol), Zyprexa® (olanzapine), and Trevilor® (≥ 1/10.000 and < 1/1000).
CONCLUSION
The risk and frequency of CAE, as reported in the SmPCs, varied significantly among substances and between groups. There are more reports for AP than AD. The AP with the most frequently reported CAE (QT prolongation and Torsade de Pointes tachycardia) was Serdolect®; for AD, Zoloft® (QT prolongation, Torsade de Pointes tachycardia) and Trevilor® (Torsade de Pointes tachycardia and ventricular tachycardia) carried a higher cardiac risk.
Topics: Antidepressive Agents; Antipsychotic Agents; Arrhythmias, Cardiac; Germany; Humans; Long QT Syndrome; Tachycardia, Ventricular; Torsades de Pointes
PubMed: 33230596
DOI: 10.1007/s00228-020-03049-x