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Swiss Medical Weekly Aug 2019Drug-drug interaction (DDI) screening programmes aim to increase the safety of medication by issuing alerts based on the severity of DDIs, since an increased risk of...
AIMS OF THE STUDY
Drug-drug interaction (DDI) screening programmes aim to increase the safety of medication by issuing alerts based on the severity of DDIs, since an increased risk of adverse drug events has been reported for some DDIs (clinically relevant alerts). However, not all DDI alerts may be clinically relevant, depending on the clinical decision support system (CDSS) interaction tool used and the target population. There are few data about the frequency and relevance of DDIs in the paediatric population. The objective of this study was to evaluate the prevalence and appropriateness of high-risk DDI alerts (drug combinations that are rated as “contraindicated” or “contraindicated by precaution” according to the Swiss CDSS interaction tool Pharmavista® (HCI Solutions AG, Bern, Switzerland)) in paediatric inpatients.
METHODS
We carried out a retrospective, single-centre study examining a cohort of paediatric cases hospitalised between January and May 2017 on the surgery/orthopaedic and oncology wards at the University of Basel Children’s Hospital (UKBB), Switzerland. Drugs administered to the patients concomitantly were obtained from the medical records. DDI screening was performed using Pharmavista®. All DDIs detected were documented with their severity grading for each hospital day per case. The clinical relevance of DDI alerts for drug combinations rated as contraindicated or contraindicated by precaution was critically evaluated by a literature review.
RESULTS
A total of 300 patient cases were assessed for “contraindicated” or “contraindicated by precaution” DDI alerts. Of these, none had “contraindicated” and five had DDI alerts rated as “contraindicated by precaution” (1.7%, 95% CI 0.6–4.1%). The corresponding drug combinations were tramadol/fentanyl/morphine-nalbuphine (n = 3), droperidol-ondansetron (n = 1) and methotrexate-metamizole (n = 1), given for a duration of 1–2 days. Adverse drug events (ADEs) due to these three combinations (QT prolongation with the combination droperidol-ondansetron, reduced effect of opioid agonists with nalbuphine and increased haematotoxicity with methotrexate-metamizole) were not documented in the patients’ medical records.
CONCLUSIONS
The low prevalence of contraindicated DDIs suggests that Pharmavista® has a low risk of over-alerting when used in a Swiss paediatric hospital. However, the current literature suggests that the severity rating of established contraindicated DDIs could be partially downgraded, and that patient/population-specific evaluations of DDI alerts are needed.
Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Decision Support Systems, Clinical; Drug Interactions; Female; Hospitalization; Hospitals, Pediatric; Humans; Male; Medication Systems, Hospital; Prevalence; Retrospective Studies; Switzerland
PubMed: 31422575
DOI: 10.4414/smw.2019.20103 -
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 -
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 -
Anaesthesia Oct 2019We randomly allocated 50 women scheduled for radical mastectomy to pectoral nerves-2 (PECS-2) block (n = 25) or no block (n = 25), 20 and 22 of whom we analysed for... (Randomized Controlled Trial)
Randomized Controlled Trial
We randomly allocated 50 women scheduled for radical mastectomy to pectoral nerves-2 (PECS-2) block (n = 25) or no block (n = 25), 20 and 22 of whom we analysed for the primary outcome of a cumulative 24-h postoperative morphine dose. We gave intra-operative sufentanil, magnesium, dexamethasone and droperidol. Participants received regular postoperative paracetamol, ibuprofen and patient-controlled intravenous morphine. Pectoral nerves-2 block reduced mean (SD) cumulative 24 h postoperative morphine dose from 9.7 (8.9) mg to 5.0 (5.4) mg and 48 h morphine dose from 12.8 (12.5) mg to 6.0 (6.5) mg, p = 0.04 for both. The mean (SD) pain scores 24 h and 48 h after surgery were similar with or without block: 0.8 (1.4) vs. 1.2 (1.9), p = 0.39; and 0.2 (0.4) vs. 0.9 (1.8), p = 0.09, respectively. Rates of postoperative nausea, vomiting and pruritus were unaffected. Rates of chronic pain at six postoperative months were 2/19 and 2/18 after block and no block, respectively, p = 0.95.
Topics: Aged; Analgesics, Opioid; Breast Neoplasms; Female; Humans; Mastectomy, Radical; Middle Aged; Morphine; Nerve Block; Pain Measurement; Pain, Postoperative; Postoperative Nausea and Vomiting; Prospective Studies; Pruritus; Thoracic Nerves; Treatment Outcome
PubMed: 31273773
DOI: 10.1111/anae.14769 -
International Journal of Molecular... Apr 2019Dopamine D₂ receptors (D₂R) are known to form transient homodimer complexes, of which the increased formation has already been associated with development of...
Dopamine D₂ receptors (D₂R) are known to form transient homodimer complexes, of which the increased formation has already been associated with development of schizophrenia. Pharmacological targeting and modulation of the equilibrium of these receptor homodimers might lead to a better understanding of the critical role played by these complexes in physiological and pathological conditions. Whereas agonist addition has shown to prolong the D₂R dimer lifetime and increase the level of dimer formation, the possible influence of D₂R antagonists on dimerization has remained rather unexplored. Here, using a live-cell reporter assay based on the functional complementation of a split Nanoluciferase, a panel of six D₂R antagonists were screened for their ability to modulate the level of DR dimer formation. Incubation with the D₂R antagonist spiperone decreased the level of DR dimer formation significantly by 40-60% in real-time and after long-term (≥16 h) incubations. The fact that dimer formation of the well-studied A-DR dimer was not altered following incubation with spiperone supports the specificity of this observation. Other D₂R antagonists, such as clozapine, risperidone, and droperidol did not significantly evoke this dissociation event. Furthermore, molecular modeling reveals that spiperone presents specific Tyr199 and Phe390 conformations, compared to clozapine, which may determine D₂R homodimerization.
Topics: Clozapine; Dimerization; Dopamine D2 Receptor Antagonists; Humans; Protein Binding; Receptors, Dopamine D2; Receptors, G-Protein-Coupled; Spiperone
PubMed: 30987329
DOI: 10.3390/ijms20071686 -
The Journal of Veterinary Medical... Aug 2019The present study used data from anesthetic records to analyze variables of intracranial pressure (ICP) during brain tumor surgery or in the early postoperative period...
The present study used data from anesthetic records to analyze variables of intracranial pressure (ICP) during brain tumor surgery or in the early postoperative period as prognostic indicators in dogs. Data from 17 dogs which were scheduled to undergo elective craniotomy for brain tumor surgery from 2009 to 2012 were included. Of these, five (29.4%) died during 14 days after the surgery because of respiratory failure following pneumonia (n=2), euthanasia due to difficulty in treatment of status epilepticus (n=1), tumor-bed hematoma (n=1), and unknown reason (n=1). In the 12 surviving dogs, neurological signs were improved or resolved at discharge. All dogs were administered midazolam and droperidol-fentanyl as premedication. General anesthesia was induced using propofol maintained on isoflurane and oxygen. Direct ICP was obtained via a Codman Microsensor strain gauge transducer. ICP hypertension (>13 mmHg) measured after 15 min of recovery from the moment after discontinuation of anesthesia by turning off the vaporizer dial was associated with poor prognosis (odds ratio, 20.00; 95% confidence interval, 1.39-287.60, P=0.028). This suggests that intracranial pressure influences the postoperative mortality rate in dogs undergoing brain tumor surgery.
Topics: Anesthesia, General; Animals; Brain Neoplasms; Craniotomy; Dog Diseases; Dogs; Intracranial Hypertension; Postoperative Period; Prognosis
PubMed: 30982789
DOI: 10.1292/jvms.18-0475 -
Journal of Pain Research 2019Acute abdominal pain (AAP) comprises up to 10% of all emergency department (ED) visits. Current pain management practice is moving toward multi-modal analgesia regimens... (Review)
Review
BACKGROUND
Acute abdominal pain (AAP) comprises up to 10% of all emergency department (ED) visits. Current pain management practice is moving toward multi-modal analgesia regimens that decrease opioid use.
OBJECTIVE
This project sought to determine whether, in patients with AAP (population), does administration of butyrophenone antipsychotics (intervention) compared to placebo, usual care, or opiates alone (comparisons) improve analgesia or decrease opiate consumption (outcomes)?
METHODS
A structured search was performed in Cochrane CENTRAL, CINAHL, Database of Abstracts of Reviews of Effects, Directory of Open Access Journals, Embase, IEEE-Xplorer, Latin American and Caribbean Health Sciences Literature, Magiran, PubMed, Scientific Information Database, Scopus, TÜBİTAK ULAKBİM, and Web of Science. Clinical trial registries (ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and Australian New Zealand Clinical Trials Registry), relevant bibliographies, and conference proceedings were also searched. Searches were not limited by date, language, or publication status. Studies eligible for inclusion were prospective randomized clinical trials enrolling patients (age ≥18 years) with AAP treated in acute care environments (ED, intensive care unit, postoperative). The butyrophenone must have been administered either intravenously or intra-muscularly. Comparison groups included placebo, opiate only, corticosteroids, non-steroidal anti-inflammatory drugs, or acetaminophen.
RESULTS
We identified 7,217 references. Six studies met inclusion criteria. One study assessed ED patients with AAP associated with gastroparesis, whereas five studies assessed patients with postoperative AAP: abdominal hysterectomy (n=4), sleeve gastrectomy (n=1). Three of four studies found improvements in pain intensity with butyrophenone use. Three of five studies reported no change in postoperative opiate consumption, while two reported a decrease. One ED study reported no change in patient satisfaction, while one postoperative study reported improved satisfaction scores. Both extrapyramidal side effects (n=3) and sedation (n=3) were reported as unchanged.
CONCLUSION
Based on available evidence, we cannot draw a conclusion on the efficacy or benefit of neuroleptanalgesia in the management of patients with AAP. However, preliminary data suggest that it may improve analgesia and decrease opiate consumption.
PubMed: 30881092
DOI: 10.2147/JPR.S187798 -
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 -
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 -
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