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The American Journal of Emergency... Mar 2022Droperidol is a butyrophenone that has recently been reintroduced after a United States Food and Drug Administration (US FDA) black box warning in 2001. Evidence...
INTRODUCTION
Droperidol is a butyrophenone that has recently been reintroduced after a United States Food and Drug Administration (US FDA) black box warning in 2001. Evidence demonstrates utility in a variety of clinical conditions.
OBJECTIVE
This paper provides evidence-based updates concerning the use of droperidol for the emergency clinician.
DISCUSSION
Droperidol received a black box warning by the US FDA in 2001 due to concerns for QT prolongation and torsades de pointes; however, reevaluation of the available data suggests droperidol is a safe and efficacious medication. It can be used in the emergency department (ED) setting for many conditions, including acute agitation, headaches, vertigo, nausea, and vomiting. Extensive literature supports that the QT-prolonging effects are transient and that the risk of torsades de pointes is rare with doses utilized in the ED. An electrocardiogram does not need to be routinely obtained before droperidol use but should be considered in patients at high risk for QT prolongation.
CONCLUSIONS
Current evidence suggests that droperidol is a safe and effective medication for treating nausea and vomiting, headache, vertigo, and agitation in the ED setting.
Topics: Droperidol; Emergency Medicine; Headache; Humans; Long QT Syndrome; Nausea; Torsades de Pointes; United States; Vertigo; Vomiting
PubMed: 35063889
DOI: 10.1016/j.ajem.2022.01.011 -
The American Journal of Emergency... Feb 2022To assess the QTc interval variation after low-dose droperidol in a population of undifferentiated, stable, and non-agitated patients receiving droperidol in the... (Observational Study)
Observational Study
OBJECTIVE
To assess the QTc interval variation after low-dose droperidol in a population of undifferentiated, stable, and non-agitated patients receiving droperidol in the emergency department.
METHODS
Prospective cohort study of patients aged ≥12 years of age who received low-dose droperidol (≤ 2.5 mg) for indications other than acute behavioral disturbances. QTc intervals were monitored in real-time during pre-specified observation periods in the ED. Primary outcome was variation of QTc interval after droperidol administration, defined as the maximum delta (change) of QTc interval. Other outcomes included proportion of patients with a QTc ≥ 500 ms after droperidol, delta ≥ +60 ms, and incidence of clinical adverse events. Patients were monitored up to 30 min after IV bolus and up to 46 min after infusion.
RESULTS
A total of 68 patients were included (mean age 42.1 years, 66.2% females). The median dose of droperidol was 1.875 mg (range 0.625 mg, 2.5 mg) and 94.1% received droperidol for headache management. Most patients received droperidol as a 2-min bolus (n = 41, 60.3%). The mean maximum delta of QTc interval after droperidol across all 68 patients was +29.9 ms (SD 15). A total of 12 patients (17.6%) experienced a QTc interval ≥ 500 ms during the observation period after droperidol, and 3 patients (4.4%) had a delta QTc ≥ +60 ms. There were no serious arrhythmias, such as TdP, or deaths among the 68 participants in this study (0/68). However, 13.2% (n = 9) had at least one non-serious adverse event including restlessness and/or anxiety.
CONCLUSION
The QTc interval slightly increased after droperidol administration, but these prolongations were brief, mostly below 500 msec and did not lead to serious arrhythmias. The yield of continuous cardiac monitoring in patients receiving low doses of droperidol is likely low.
Topics: Adjuvants, Anesthesia; Adult; Antiemetics; Dose-Response Relationship, Drug; Droperidol; Emergency Service, Hospital; Female; Humans; Long QT Syndrome; Male; Prospective Studies; Young Adult
PubMed: 34959024
DOI: 10.1016/j.ajem.2021.12.039 -
RSC Medicinal Chemistry Nov 2021Tuberculosis (TB), caused by (), is a deadly bacterial disease. Drug-resistant strains of make eradication of TB a daunting task. Overexpression of the enhanced...
Tuberculosis (TB), caused by (), is a deadly bacterial disease. Drug-resistant strains of make eradication of TB a daunting task. Overexpression of the enhanced intracellular survival (Eis) protein by confers resistance to the second-line antibiotic kanamycin (KAN). Eis is an acetyltransferase that acetylates KAN, inactivating its antimicrobial function. Development of Eis inhibitors as KAN adjuvant therapeutics is an attractive path to forestall and overcome KAN resistance. We discovered that an antipsychotic drug, haloperidol (HPD, ), was a potent Eis inhibitor with IC = 0.39 ± 0.08 μM. We determined the crystal structure of the Eis-haloperidol () complex, which guided synthesis of 34 analogues. The structure-activity relationship study showed that in addition to haloperidol (), eight analogues, some of which were smaller than , potently inhibited Eis (IC ≤ 1 μM). Crystal structures of Eis in complexes with three potent analogues and droperidol (DPD), an antiemetic and antipsychotic, were determined. Three compounds partially restored KAN sensitivity of a KAN-resistant strain K204 overexpressing Eis. The Eis inhibitors generally did not exhibit cytotoxicity against mammalian cells. All tested compounds were modestly metabolically stable in human liver microsomes, exhibiting 30-60% metabolism over the course of the assay. While direct repurposing of haloperidol as an anti-TB agent is unlikely due to its neurotoxicity, this study reveals potential approaches to modifying this chemical scaffold to minimize toxicity and improve metabolic stability, while preserving potent Eis inhibition.
PubMed: 34825186
DOI: 10.1039/d1md00239b -
The American Journal of Emergency... Jan 2022Safe and effective tranquilization of the acutely agitated patient is challenging, and head-to-head comparisons of medications are limited. We aimed to identify the most... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Safe and effective tranquilization of the acutely agitated patient is challenging, and head-to-head comparisons of medications are limited. We aimed to identify the most optimal agent(s) for rapid tranquilization of the severely agitated patient in the emergency department (ED).
METHODS
The protocol for systematic review was registered (PROSPERO; CRD42020212534). We searched MEDLINE, Embase, PsycINFO, and Cochrane Database/CENTRAL from inception to June 2, 2021. We limited studies to randomized controlled trials that enrolled adult ED patients with severe agitation and compared drugs for rapid tranquilization. Predetermined outcomes were: 1) Adequate sedation within 30 min (effectiveness), 2) Immediate, serious adverse event - cardiac arrest, ventricular tachydysrhythmia, endotracheal intubation, laryngospasm, hypoxemia, hypotension (safety), and 3) Time to adequate sedation (effect onset). We extracted data according to PRISMA-NMA and appraised trials using Cochrane RoB 2 tool. We performed Bayesian network meta-analysis (NMA) using a Markov Chain Monte Carlo method with random-effects model and vague prior distribution to calculate odds ratios with 95% credible intervals for dichotomous outcomes and frequentist NMA to calculate mean differences with 95% confidence intervals for continuous outcomes. We assessed confidence in results using CINeMA. We used surface under the cumulative ranking (SUCRA) curves to rank agent(s) for each outcome.
RESULTS
Eleven studies provided data for effectiveness (1142 patients) and safety (1147 patients). Data was insufficient for effect onset. The NMA found that ketamine (SUCRA = 93.0%) is most likely to have superior effectiveness; droperidol-midazolam (SUCRA = 78.8%) is most likely to be safest. There are concerns with study quality and imprecision. Quality of the point estimates varied for effectiveness but mostly rated "very low" for safety.
CONCLUSIONS
Available evidence suggests that ketamine and droperidol have intermediate effectiveness for rapid tranquilization of the severely agitated patient in the ED. There is insufficient evidence to definitively determine which agent(s) may be safest or fastest-acting. Further, direct-comparison study of ketamine and droperidol is recommended.
Topics: Adult; Droperidol; Emergence Delirium; Emergency Service, Hospital; Humans; Ketamine; Network Meta-Analysis; Psychomotor Agitation; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 34823192
DOI: 10.1016/j.ajem.2021.11.011 -
Medical Principles and Practice :... 2022Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among...
INTRODUCTION
Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among adults and older patients have been reported named cannabis hyperemesis syndrome (CHS). CHS is a condition that leads to repeated and severe N/V in long-term users of cannabinoids.
OBJECTIVE
The aim of this study was to outline current treatments for the management of CHS.
METHODS
A systematic review was conducted using PubMed, Ovid MEDLINE, Cochrane Central, EMBASE, and Google Scholar. Databases were used to search for articles on CHS published from January 2009 to June 2021, yielding 225 results of which 17 were deemed relevant and underwent review by 2 separate reviewers.
RESULTS
The duration of cannabis administration ranged between 6 months to 11 years may precipitate symptoms of CHS. The Rome IV diagnostic criteria of CHS require cannabinoid use and persistence of N/V symptoms for at least the past 6 months. Cannabis cessation is noted to be the most successful management, but other treatments also demonstrated symptom relief; these include hot water hydrotherapy, topical capsaicin cream, haloperidol, droperidol, benzodiazepines, propranolol, and aprepitant administration.
CONCLUSION
More research on CHS is needed to enhance knowledge translation, education, and create awareness in the medical community on the side effects of cannabinoids and to propose the best treatment options.
Topics: Adult; Analgesics; Cannabinoids; Cannabis; Humans; Marijuana Abuse; Syndrome; Vomiting
PubMed: 34724666
DOI: 10.1159/000520417 -
Microsystems & Nanoengineering 2021Cardiovascular disease (CVD) is the number one cause of death in humans. Arrhythmia induced by gene mutations, heart disease, or hERG K channel inhibitors is a serious...
Cardiovascular disease (CVD) is the number one cause of death in humans. Arrhythmia induced by gene mutations, heart disease, or hERG K channel inhibitors is a serious CVD that can lead to sudden death or heart failure. Conventional cardiomyocyte-based biosensors can record extracellular potentials and mechanical beating signals. However, parameter extraction and examination by the naked eye are the traditional methods for analyzing arrhythmic beats, and it is difficult to achieve automated and efficient arrhythmic recognition with these methods. In this work, we developed a unique automated template matching (ATM) cardiomyocyte beating model to achieve arrhythmic recognition at the single beat level with an interdigitated electrode impedance detection system. The ATM model was established based on a rhythmic template with a data length that was dynamically adjusted to match the data length of the target beat by spline interpolation. The performance of the ATM model under long-term astemizole, droperidol, and sertindole treatment at different doses was determined. The results indicated that the ATM model based on a random rhythmic template of a signal segment obtained after astemizole treatment presented a higher recognition accuracy (100% for astemizole treatment and 99.14% for droperidol and sertindole treatment) than the ATM model based on arrhythmic multitemplates. We believe this highly specific ATM method based on a cardiomyocyte beating model has the potential to be used for arrhythmia screening in the fields of cardiology and pharmacology.
PubMed: 34567738
DOI: 10.1038/s41378-021-00251-4 -
Current Medical Research and Opinion Dec 2021Inhalative anesthesia is of common use, but is generally known to potentiate postoperative nausea and vomiting (PONV). With an internal change of anesthesia regimen from... (Observational Study)
Observational Study
OBJECTIVES
Inhalative anesthesia is of common use, but is generally known to potentiate postoperative nausea and vomiting (PONV). With an internal change of anesthesia regimen from total intravenous anesthesia (TIVA) to isoflurane (in terms of myocardial protection) in cardiac anesthesia a higher incidence of PONV was to be expected. Therefore, we evaluated the incidence of PONV after the simultaneous implementation of PONV prophylaxis.
METHODS
The incidence of PONV, prospectively assessed in 197 cardiac surgery patients (68 ± 10.4, 66.5% male) having isoflurane plus dual PONV prophylaxis with dexamethasone and droperidol, was compared with previous data of 190 controls (67 ± 9.6, 71% male) having TIVA without and with single or dual PONV prophylaxis ( = 64 dexamethasone and droperidol, = 25 dexamethasone, = 101 only TIVA), and the Apfel-scoring (0-4 depending on PONV-risk). DRKS00014275. Statistics: Chi-test, < .05 (Bonferroni).
RESULTS
The incidence of PONV under isoflurane with antiemetic prophylaxis was 20.8% (95% confidence interval (CI) 15.4; 27.4) compared to 30.5% (95%CI 24; 37.6) under TIVA ( = .029; dexamethasone and droperidol 23.4% (95%CI 13.8; 35.7); dexamethasone 32% (95%CI 14.9; 53.5); only TIVA 34.7% (95%CI 25.5; 44.8)), but was not lower in high-risk patients than predicted according to Apfel-scoring 4 (71.4 vs. 78%).
CONCLUSION
In cardiac anesthesia, the use of isoflurane is not at the expense of PONV when using a risk-independent two-drug-prophylaxis. It is even beneficial resulting surprisingly in a lower incidence of PONV than under TIVA unless with and without prophylaxis. Patients with the highest risk for PONV and receiving isoflurane should receive a third antiemetic prophylactic drug.
Topics: Anesthesia, Cardiac Procedures; Anesthesia, General; Antiemetics; Female; Humans; Isoflurane; Male; Postoperative Nausea and Vomiting; Propofol
PubMed: 34515599
DOI: 10.1080/03007995.2021.1980776 -
Journal of Neurosurgical Anesthesiology Oct 2022Low-dose droperidol has been reported to suppress the amplitude of transcranial electrical motor-evoked potentials (TCE-MEPs), but no randomized controlled trials have... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Low-dose droperidol has been reported to suppress the amplitude of transcranial electrical motor-evoked potentials (TCE-MEPs), but no randomized controlled trials have been conducted to assess this. This randomized, double-blinded, placebo-controlled trial aimed to test the hypothesis that low-dose droperidol reduced TCE-MEP amplitudes.
METHODS
Twenty female patients with adolescent idiopathic scoliosis, aged between 12 and 20 years, and scheduled to undergo corrective surgery were randomly allocated to receive droperidol (20 µg/kg) or 0.9% saline. After recording baseline TCE-MEPs, the test drug was administered, following which TCE-MEP recordings were carried out every 2 minutes for up to 10 minutes. The primary outcome was the minimum relative TCE-MEP amplitude (peak-to-peak amplitude, percentage of baseline value) recorded in the left tibialis anterior muscle. Secondary outcomes included minimum relative MEP amplitudes recorded from all other muscle groups monitored in the study. Data are expressed as medians (interquartile range).
RESULTS
The TCE-MEP amplitude of the left tibialis anterior muscle was significantly reduced following droperidol administration compared with saline (37% [30% to 55%] vs. 76% [58% to 93%], respectively, P <0.01). In the other muscles, the amplitudes were reduced in the droperidol group, except for the bilateral abductor pollicis brevis and the left quadriceps femoris muscles. The relative amplitude of the bilateral F waves recorded from the gastrocnemius was decreased in the droperidol group.
CONCLUSIONS
Low-dose droperidol (20 µg/kg) reduced TCE-MEP amplitudes. Anesthesiologists should pay attention to the timing of droperidol administration during intraoperative TCE-MEP recordings, even if used in a low dose.
Topics: Adolescent; Adult; Child; Droperidol; Evoked Potentials, Motor; Female; Humans; Monitoring, Intraoperative; Muscle, Skeletal; Young Adult
PubMed: 34411060
DOI: 10.1097/ANA.0000000000000784 -
Journal of Paediatrics and Child Health Jan 2022Studies reporting factors associated with paediatric/adolescent acute behavioural disturbance (ABD) in the Emergency Department (ED) are lacking. The aim of this study...
AIM
Studies reporting factors associated with paediatric/adolescent acute behavioural disturbance (ABD) in the Emergency Department (ED) are lacking. The aim of this study is to describe paediatric/adolescent ED presentations involving ABD events.
METHODS
A retrospective chart review of presentations involving ABD events, identified via hospital security log, to a tertiary referral paediatric ED during the 2017 calendar year. Data reported included: cause of presentation, use of sedation/physical restraint, ED/inpatient length of stay (LOS) and time requiring security staff presence.
RESULTS
From 280 reported ABD episodes 26 were excluded leaving 254 events involving 150 patients across 233 presentations of whom 38 (25.3%) presented on multiple occasions. Median age was 14 years (interquartile range (IQR): 13-16), 132/233 (56.7%) were female, 167/233 (71.7%) primary mental health complaints, 30/233 (12.9%) deliberate self-harm, 18/233 (7.7%) deliberate self-poisoning, 11/233 (4.7%) acute intoxication and 7/233 (3.0%) other. Transport to hospital involved police and ambulance in 124/233 (53.2%), ambulance only 71/233 (30.5%), police only 16/233 (6.9%), relative or carer 20/233 (8.6%), with self-presentation in 2/233 (0.9%). Sedation or physical restraint was used in 81/233 (34.8%), both 38/233 (16.3%), restraint only 26/233 (11.2%) and sedation only 17/234 (7.3%). Intra-muscular droperidol accounted for 57/96 (59.4%) sedations, IM/IV benzodiazepines 15/96 (15.6%), IM/IV ketamine 5/96 (5.2%) and 19/96 (19.8%) other. Discharge from ED occurred in 171/233 (73.1%) with median ED LOS 5.1 h (IQR: 3.5-7.7) and median hospital LOS 92.4 h (IQR: 47.5-273.4) for those admitted. The Mental Health Act was utilised in 183/233 (78.5%) presentations. Median security staff time requirement per presentation was 2.4 h (IQR: 1.0-3.9).
CONCLUSIONS
Paediatric/adolescent ED presentations involving ABD are primarily due to mental health complaints. Less than half require the use of sedation/physical restraint. Time requiring security staff involvement is a significant resource consumption.
Topics: Adolescent; Child; Emergency Service, Hospital; Female; Humans; Length of Stay; Patient Discharge; Police; Retrospective Studies
PubMed: 34375471
DOI: 10.1111/jpc.15668 -
Cureus Jun 2021Prophylactic doses of droperidol are effective in preventing postoperative nausea and vomiting (PONV). However, due to concerns of QT interval prolongation and...
Prophylactic doses of droperidol are effective in preventing postoperative nausea and vomiting (PONV). However, due to concerns of QT interval prolongation and ventricular arrhythmias, the safety of droperidol for PONV prophylaxis has been debated. A 70-year-old woman was scheduled for total knee arthroplasty. She had a history of aortic valve replacement. Oral aprindine (40 mg/day) was prescribed. Preoperative electrocardiogram showed mild QT interval prolongation (QTc = 475 ms). Anesthesia was induced using propofol, remifentanil, and rocuronium, and maintained using desflurane, remifentanil, and a bolus dose of rocuronium. The surgery was uneventful. At the time of skin closure, droperidol (1.25 mg) was administered intravenously for PONV prophylaxis. Twenty-three minutes after administration of droperidol, a sudden onset of premature cardiac contraction was observed, which progressed directly to ventricular tachycardia and atrioventricular block. Arrhythmia due to droperidol-induced QT interval prolongation was strongly suspected. Intravenous magnesium sulfate (2 g) and atropine (0.5 mg) were administered immediately. The ventricular tachycardia resolved quickly after the magnesium injection. Following the resolution of the arrhythmia, the patient was extubated. The patient experienced ventricular tachycardia after a prophylactic dose of droperidol that resulted from QT interval prolongation due to the preoperative medication. It may be prudent to avoid even low-dose droperidol in the background of already present QT prolongation, especially when multiple putative QT-prolonging drugs are used.
PubMed: 34277183
DOI: 10.7759/cureus.15560