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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 -
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 -
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 -
Federal Practitioner : For the Health... Apr 2024Acute agitation frequently occurs in the emergency department. Appropriate management is critical for the safety of all parties involved. Benzodiazepines and...
BACKGROUND
Acute agitation frequently occurs in the emergency department. Appropriate management is critical for the safety of all parties involved. Benzodiazepines and antipsychotics are commonly used for agitation, but safety concerns exist with these medications in older adults, even with acute use. The purpose of this study was to compare prescribing practices of anti-agitation medications between adults aged 18 to 64 years and those aged ≥ 65 years.
METHODS
This study was a retrospective chart review of patients who presented to the Veteran Affairs Southern Nevada Healthcare System emergency department and received haloperidol, droperidol, lorazepam, olanzapine, or ziprasidone from August 1, 2019, to July 31, 2022. Veterans were excluded if they had alcohol intoxication, alcohol withdrawal, benzodiazepine withdrawal, or medication administration unrelated to agitation. Safety outcomes included oxygen saturation < 95%, supplemental oxygen use, intubation, QTc prolongation, and new hypotension within 1 hour of medication administration.
RESULTS
For the 232 patients who met inclusion criteria, baseline characteristics differed significantly. When comparing patients aged 18 to 64 years and those aged ≥ 65 years, the younger cohort had higher rates of substance use disorder diagnosis (55.3% vs 27.5%, < .001), positive urine drug screen (69.7% vs 22.5%, < .001), and 72-hour legal hold (59.9% vs 32.5%, < .001), and lower rates of cognitive impairment or dementia (0.7% vs 48.8%, < .001), and altered mental status-related diagnosis (2.0% vs 18.8%, < .001). Anti-agitation medication selection significantly differed based on age ( = .02). Other than lorazepam ( = .007), no significant differences were noted in the dose ordered. No significant differences were observed for safety outcomes or additional anti-agitation doses.
CONCLUSIONS
Anti-agitation prescribing practices may differ between adults aged 18 to 64 years and those aged ≥ 65 years. The findings of this study also suggest that the most common agitation etiologies may differ based on patient age. Additional higher-quality studies are needed to further explore acute agitation in older adults.
PubMed: 38813266
DOI: 10.12788/fp.0456 -
Academic Emergency Medicine : Official... Aug 2019The objective was to separately compare effectiveness of 1.25 mg of intravenous (IV) droperidol and 8 mg of IV ondansetron with 0.9% saline placebo for adult emergency... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The objective was to separately compare effectiveness of 1.25 mg of intravenous (IV) droperidol and 8 mg of IV ondansetron with 0.9% saline placebo for adult emergency department (ED) patients with nausea. A novel primary outcome measure, expected to aid clinical interpretation of reported results, was employed.
METHODS
A randomized controlled trial was conducted at the three EDs of Monash Health, Melbourne, Australia. The design was to demonstrate superiority of the active drugs over placebo. The primary outcome measure of symptom improvement was defined as a visual analog scale (VAS) rating change of -8 mm or more from baseline at 30 minutes posttreatment. Mean VAS changes per group and percentages experiencing the desired treatment effect were also compared. The study was concluded after recruitment of 215 of the planned 378 patients, as interim analysis confirmed that continuation could not result in a finding of superiority.
RESULTS
Of 215 patients, 73 (34%), 71 (33%), and 71 (33%) received droperidol, ondansetron, and placebo. Symptom improvement occurred in 75% (95% confidence interval [CI] = 64% to 85%), 80% (95% CI = 69% to 89%), and 76% (95% CI = 64% to 85%), respectively. Mean VAS changes were -29 mm (95% CI = -36 to -23 mm), -34 mm (95% CI = -41 to -28 mm), and -24 mm (95% CI = -29 to -19 mm), respectively. Desired treatment effects were experienced by 77% (95% CI = 65% to 86%), 73% (95% CI = 61% to 83%), and 59% (95% CI = 47% to 71%), respectively.
CONCLUSION
For adult ED patients with nausea, superiority was not demonstrated for droperidol or ondansetron over placebo.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Australia; Double-Blind Method; Droperidol; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Nausea; Ondansetron; Visual Analog Scale; Young Adult
PubMed: 30368981
DOI: 10.1111/acem.13650 -
Nature Jul 2017The cannabinoid receptor 1 (CB) is the principal target of the psychoactive constituent of marijuana, the partial agonist Δ-tetrahydrocannabinol (Δ-THC). Here we...
The cannabinoid receptor 1 (CB) is the principal target of the psychoactive constituent of marijuana, the partial agonist Δ-tetrahydrocannabinol (Δ-THC). Here we report two agonist-bound crystal structures of human CB in complex with a tetrahydrocannabinol (AM11542) and a hexahydrocannabinol (AM841) at 2.80 Å and 2.95 Å resolution, respectively. The two CB-agonist complexes reveal important conformational changes in the overall structure, relative to the antagonist-bound state, including a 53% reduction in the volume of the ligand-binding pocket and an increase in the surface area of the G-protein-binding region. In addition, a 'twin toggle switch' of Phe200 and Trp356 (superscripts denote Ballesteros-Weinstein numbering) is experimentally observed and appears to be essential for receptor activation. The structures reveal important insights into the activation mechanism of CB and provide a molecular basis for predicting the binding modes of Δ-THC, and endogenous and synthetic cannabinoids. The plasticity of the binding pocket of CB seems to be a common feature among certain class A G-protein-coupled receptors. These findings should inspire the design of chemically diverse ligands with distinct pharmacological properties.
Topics: Binding Sites; Cannabinoid Receptor Agonists; Crystallography, X-Ray; Dronabinol; Droperidol; Heterotrimeric GTP-Binding Proteins; Humans; Ligands; Molecular Docking Simulation; Protein Binding; Protein Conformation; Receptor, Cannabinoid, CB1
PubMed: 28678776
DOI: 10.1038/nature23272 -
Brazilian Journal of Anesthesiology... 2015The prophylactic effect of ondansetron on subarachnoid morphine-induced pruritus is controversial, while evidence suggests that droperidol prevents pruritus. The aim of... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
The prophylactic effect of ondansetron on subarachnoid morphine-induced pruritus is controversial, while evidence suggests that droperidol prevents pruritus. The aim of this study is to compare the effects of droperidol and ondansetron on subarachnoid morphine-induced pruritus.
METHODS
180 ASA I or II patients scheduled to undergo cesarean sections under subarachnoid anesthesia combined with morphine 0.2mg were randomized to receive, after the child's birth, metoclopramide 10mg (Group I - control), droperidol 2.5mg (Group II) or ondansetron 8mg (Group III). Postoperatively, the patients were assessed for pruritus (absent, mild, moderate or severe) or other side effects by blinded investigators. Patients were also blinded to their group allocation. The tendency to present more severe forms of pruritus was compared between groups. NNT was also determined.
RESULTS
Patients assigned to receive droperidol [Proportional odds ratio: 0.45 (95% confidence interval 0.23-0.88)] reported less pruritus than those who received metoclopramide. Ondansetron effect was similar to metoclopramide [Proportional odds ratio: 0.95 (95% confidence interval 0.49-1.83)]. The NNT for droperidol and ondansetron was 4.0 and 14.7, respectively.
CONCLUSIONS
Ondansetron does not inhibit subarachnoid morphine-induced pruritus.
Topics: Adult; Analgesics, Opioid; Anesthesia, Obstetrical; Cesarean Section; Double-Blind Method; Droperidol; Female; Humans; Metoclopramide; Morphine; Ondansetron; Pregnancy; Pruritus
PubMed: 26123142
DOI: 10.1016/j.bjane.2013.11.005 -
Academic Emergency Medicine : Official... Apr 2021The optimal agent to treat acute agitation in the emergency department (ED) has not been determined. The objective of this study was to compare the effectiveness and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The optimal agent to treat acute agitation in the emergency department (ED) has not been determined. The objective of this study was to compare the effectiveness and safety of intramuscular droperidol, ziprasidone, and lorazepam for acute agitation in the ED.
METHODS
This was a randomized, double-blind trial of ED patients with acute agitation requiring parenteral sedation. The study was conducted under exception from informed consent (21 CFR 50.24) from July 2004 to March 2005. Patients were randomized to receive 5 mg of droperidol, 10 mg of ziprasidone, 20 mg of ziprasidone, or 2 mg of lorazepam intramuscularly. We recorded Altered Mental Status Scale (AMSS) scores, nasal end-tidal carbon dioxide (ETCO ), and pulse oximetry (SpO ) at 0, 15, 30, 45, 60, 90, and 120 minutes as well as QTc durations and dysrhythmias. Respiratory depression was defined as a change in ETCO consistent with respiratory depression or SpO < 90%. The primary outcome was the proportion of patients adequately sedated (AMSS ≤ 0) at 15 minutes.
RESULTS
We enrolled 115 patients. Baseline AMSS scores were similar between groups. For the primary outcome, adequate sedation at 15 minutes, droperidol administration was effective in 16 of 25 (64%) patients, compared to seven of 28 (25%) for 10 mg of ziprasidone, 11 of 31 (35%) for 20 mg of ziprasidone, and nine of 31 (29%) for lorazepam. Pairwise comparisons revealed that droperidol was more effective that the other medications, with 39% (95% confidence interval [CI] = 3% to 54%) more compared to 20 mg of ziprasidone and 33% (95% CI = 8% to 58%) more compared to lorazepam. There was no significant difference between groups in need of additional rescue sedation. Numerically, respiratory depression was lower with droperidol (3/25 [12%]) compared to 10 mg of ziprasidone (10/28 [36%]), 20 mg of ziprasidone (12/31 [39%]), or lorazepam (15/31 [48%]). One patient receiving 20 mg of ziprasidone required intubation to manage an acute subdural hematoma. No patients had ventricular dysrhythmias. QTc durations were similar in all groups.
CONCLUSIONS
Droperidol was more effective than lorazepam or either dose of ziprasidone for the treatment of acute agitation in the ED and caused fewer episodes of respiratory depression.
Topics: Antipsychotic Agents; Droperidol; Emergency Service, Hospital; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Lorazepam; Piperazines; Psychomotor Agitation; Thiazoles
PubMed: 32888340
DOI: 10.1111/acem.14124