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Clinical Practice and Cases in... May 2023Phantom limb pain (PLP) is a poorly understood phenomenon experienced by amputees. The pain is typically classified as neuropathic, and there is no established...
INTRODUCTION
Phantom limb pain (PLP) is a poorly understood phenomenon experienced by amputees. The pain is typically classified as neuropathic, and there is no established first-line therapy. Droperidol is an antipsychotic with a wide array of pharmacologic activity including gamma-aminobutyric acid-A channel modulation, μ opioid receptor potentiation, dopamine-2-receptor blockade, and alpha-2-receptor agonism. Due to this broad therapeutic activity, droperidol is used for many off-label indications.
CASE REPORT
Our patient was a 25-year-old male with a history of lower limb amputation who presented for evaluation and management of an acute exacerbation of PLP. On arrival, the patient was in 10/10 pain (numeric pain rating scale) described as cramping and burning. He had been previously successfully managed with subdissociative ketamine. However, during a recent exacerbation he experienced an emergence reaction to ketamine. Literature guiding pharmacotherapy in the management of PLP is sparse and of low quality. Based on the prior emergence reaction to subdissociative ketamine we explored other pharmacotherapy options. Droperidol has a wide array of pharmacologic activity and is used off label for the management of some pain syndromes. Therefore, we administered an intravenous dose of droperidol 5 milligrams. Approximately 15 minutes after receiving droperidol the patient's pain was visibly improved, and 30 minutes later he rated his pain at 3/10.
CONCLUSION
The success in treating this patient provides encouragement for future research and bolsters confidence that droperidol could be another tool in the management of complex pain syndromes.
PubMed: 37285490
DOI: 10.5811/cpcem.1405 -
Saudi Journal of Anaesthesia 2019In this review, we evaluate recent literature on use of ER granisetron in clinical practice as compared with current antiemetics and describe its potential uses for... (Review)
Review
In this review, we evaluate recent literature on use of ER granisetron in clinical practice as compared with current antiemetics and describe its potential uses for perioperative PONV prophylaxis and treatment. Recent literature was evaluated on ER granisetron use compared with currently used antiemetic agents ondansetron, droperidol, metoclopramide, promethazine, and dexamethasone with a focus on procedural anti-emesis. Though promising great effect, application of extended release granisetron to clinical use may be limited by it's increased relative cost.
PubMed: 31333369
DOI: 10.4103/sja.SJA_817_18 -
Anesthesia Progress Sep 2020
Topics: Droperidol; Humans; Postoperative Nausea and Vomiting
PubMed: 32992339
DOI: 10.2344/anpr-67-03-14 -
British Journal of Clinical Pharmacology Dec 2016Intramuscular droperidol is used increasingly for sedation of aggressive and violent patients. This study aimed to characterise the pharmacokinetics of intramuscular...
BACKGROUND
Intramuscular droperidol is used increasingly for sedation of aggressive and violent patients. This study aimed to characterise the pharmacokinetics of intramuscular droperidol in these patients to determine how rapidly it is absorbed and the expected duration of measurable drug concentrations.
METHODS
We undertook a population pharmacokinetic analysis of a subgroup of patients from a clinical trial comparing droperidol and midazolam: 17 receiving 5 mg and 24 receiving 10 mg droperidol. Droperidol was measured using high-performance liquid chromatography. Pharmacokinetic modelling was performed under a nonlinear mixed effects modelling framework (NONMEM v7.2). The model was used to simulate concentration time profiles of three typical doses, 5 mg, 10 mg and 10 mg + 10 mg repeated at 15 min.
RESULTS
A two-compartment first-order input with first-order output model fitted the data best. The absorption rate constant was poorly characterised by the data and an estimate of the first order rate constant of absorption when fixed to 10 h provided a stable model and lowest objective function. This represents extremely rapid absorption with a half-life of 5 min. The final model had a clearance of 41.9 l h and volume of distribution of the central compartment of, 73.6 l. Median and interquartile range of initial (alpha) half-life was 0.32 h (0.26-0.37 h) and second (beta) half-life was 3.0 h (2.5-3.6 h). Simulations indicate that 10 mg alone provides an 80% probability of being above the lower limit of quantification (5 μg l ) for 7 h, 2 h longer than for 5 mg. Giving two 10 mg doses increased this duration to 10 h.
CONCLUSIONS
Intramuscular droperidol is rapidly absorbed with high therapeutic concentrations after 5 and 10 mg doses, and supports clinical data in which droperidol sedates rapidly for up to 6 h.
Topics: Absorption, Physiological; Adult; Antipsychotic Agents; Computer Simulation; Droperidol; Female; Half-Life; Humans; Injections, Intramuscular; Male; Models, Biological; Predictive Value of Tests; Psychomotor Agitation; Randomized Controlled Trials as Topic
PubMed: 27530285
DOI: 10.1111/bcp.13093 -
SAGE Open Medicine 2018Droperidol is used parenterally to treat nausea and vomiting, migraine and acute behavioural disturbance. Intranasal use is not reported for droperidol. Intranasal drug...
BACKGROUND
Droperidol is used parenterally to treat nausea and vomiting, migraine and acute behavioural disturbance. Intranasal use is not reported for droperidol. Intranasal drug administration reduces need for intravenous line placement and risk of needle-stick.
OBJECTIVE
To model population pharmacokinetics of intranasal droperidol.
METHOD
Single doses of intranasal and intravenous droperidol (0.02 mg/kg) were studied in an open-label crossover-trial in seven volunteers with a 1-week washout period. Blood samples collected over 10-h were analysed by liquid chromatography tandem mass spectrometer. Droperidol plasma concentrations following intravenous and intranasal administration were subjected to non-compartmental analysis and population pharmacokinetic modelling using S-ADAPT. Monte Carlo simulations were conducted for various potential intranasal dosage regimens.
RESULTS
The droperidol concentration-time profiles following intravenous and intranasal administration were best described by a model with two equilibrating disposition compartments and linear elimination. The apparent elimination clearance for intranasal dosing was 87.9 L/h and apparent central volume of distribution 18.2 L. Monte Carlo simulations of 5 mg droperidol (corresponding to the maximum volume that can be practically administered intranasal at a time) given intranasally at 0 and 5 min or 0 and 10 min indicated peak concentrations would reach those seen at 25 min after single intravenous administration of 1.5 mg. No adverse clinical effects or QT interval prolongation were observed.
CONCLUSION
Given the reduced bioavailability of intranasal droperidol, Monte Carlo simulations suggested that it could potentially be used at a higher dose (2.5-5 mg) than currently used intravenously in clinical trials assessing the effectiveness in treatment of nausea, vomiting and migraine.
PubMed: 30574300
DOI: 10.1177/2050312118813283 -
Archives of Medical Science : AMS Apr 2015Laparoscopic cholecystectomy is associated with a high incidence of postoperative nausea and vomiting. In this study we investigated comparatively the efficacy of...
INTRODUCTION
Laparoscopic cholecystectomy is associated with a high incidence of postoperative nausea and vomiting. In this study we investigated comparatively the efficacy of combination therapy with ondansetron plus droperidol versus monotherapy with each agent alone in preventing postoperative nausea and vomiting following elective laparoscopic cholecystectomy.
MATERIAL AND METHODS
One hundred twenty-seven patients who underwent elective laparoscopic cholecystectomy under general anesthesia were included in the study, and assigned to one of the following three groups according to the antiemetic drug given intravenously at the end of the surgery: droperidol 1.25 mg in group D, ondansetron 4 mg in group O, and a combination of droperidol and ondansetron at the doses mentioned above in group D + O. Incidence of postoperative nausea and vomiting, and doses of given rescue antiemetics were recorded during the first postoperative day. The total drug cost per patient spent for postoperative nausea and vomiting management (including prophylactic antiemetics plus rescue postoperative antiemetics) was calculated.
RESULTS
Combination therapy significantly reduced postoperative nausea and vomiting at 30 min, 3 h and 6 h after surgery compared with group D (p < 0.01 for all time points) and O (p < 0.01 at 30 min, p < 0.05 at 3 h) and required less rescue antiemetic treatment (p < 0.01). Total antiemetic cost analyses revealed no significant differences among the three groups (p > 0.05).
CONCLUSIONS
Pretreatment with ondansetron plus droperidol is more effective than monotherapy in preventing postoperative nausea and vomiting following laparoscopic cholecystectomy, without increasing the cost comparatively.
PubMed: 25995753
DOI: 10.5114/aoms.2015.50968 -
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 -
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