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The Primary Care Companion For CNS... Dec 2023To assess the efficacy and safety of loxapine in acute agitation. PubMed, Cochrane database, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify...
To assess the efficacy and safety of loxapine in acute agitation. PubMed, Cochrane database, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify relevant articles published in English or French from inception to March 15, 2022. The term "Loxap*" was searched in titles and abstracts. Interventional studies that compared the effectiveness of loxapine to any other intervention (including another administration route or dosage of loxapine, other drugs, and placebo) in acute agitation were included. From the 1,435 articles initially identified, and after the assessment of 73 full texts, 7 articles were selected, encompassing 1,276 participants. Two reviewers independently extracted data of interest using a predefined form. Among included studies, 5 were double-blind, 2 were open-label, and all were randomized. The risk of bias was low for 2 studies, involving 658 participants. Four articles compared loxapine to placebo, and 3 compared it with haloperidol, aripiprazole, and droperidol. Loxapine was found to be more effective and faster regarding acute agitation control. Also, across included studies, loxapine was well-tolerated, with mildly or moderately severe adverse effects. Notwithstanding methodological limitations of the included studies, this systematic review provides reassuring results regarding the use of loxapine in acute agitation. However, further studies with methodological optimizations might be of interest. .
Topics: Humans; Loxapine; Antipsychotic Agents; Administration, Inhalation; Psychomotor Agitation; Aripiprazole; Randomized Controlled Trials as Topic
PubMed: 38134395
DOI: 10.4088/PCC.23r03552 -
Frontiers in Pharmacology 2023Despite advances in antiemetics and protocolized postoperative nausea vomiting (PONV) management, it remains one of the most common postoperative adverse events. In... (Review)
Review
Despite advances in antiemetics and protocolized postoperative nausea vomiting (PONV) management, it remains one of the most common postoperative adverse events. In patients who developed PONV despite antiemetic prophylaxis, giving a rescue treatment from the same class of medication is known to be of limited efficacy. Given the widespread use of 5-HT3 antagonists as PONV prophylaxis, another class of effective intravenous rescue antiemetic is in dire need, especially when prophylaxis fails, and rescue medication is utilized. Dopamine antagonists were widely used for the treatment of PONV but have fallen out of favor due to some of their side effect profiles. Amisulpride was first designed as an antipsychotic medication but was found to have antiemetic properties. Here we will review the historical perspective on the use of dopamine receptor antagonist antiemetics, as well as the evidence on the efficacy and safety of amisulpride.
PubMed: 38026950
DOI: 10.3389/fphar.2023.1274214 -
BMC Anesthesiology Oct 2023There are limited real-world data regarding the use of droperidol for antiemetic prophylaxis in intravenous patient-controlled analgesia (IV-PCA). This study aimed to...
BACKGROUND
There are limited real-world data regarding the use of droperidol for antiemetic prophylaxis in intravenous patient-controlled analgesia (IV-PCA). This study aimed to evaluate the antiemetic benefits and sedation effects of droperidol in morphine-based IV-PCA.
METHODS
Patients who underwent major surgery and used morphine-based IV-PCA at a medical center from January 2020 to November 2022 were retrospectively analyzed. The primary outcome was the rate of any postoperative nausea and/or vomiting (PONV) within 72 h after surgery. Propensity score matching was used to match patients with and without the addition of droperidol to IV-PCA infusate in a 1:1 ratio. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs).
RESULTS
After matching, 1,104 subjects were included for analysis. The addition of droperidol to IV-PCA reduced the risk of PONV (aOR: 0.49, 95% CI: 0.35-0.67, p < 0.0001). The antiemetic effect of droperidol was significant within 36 h after surgery and attenuated thereafter. Droperidol was significantly associated with a lower risk of antiemetic uses (aOR: 0.58, 95% CI: 0.41-0.80, p = 0.0011). The rate of unintentional sedation was comparable between the patients with (9.1%) and without (7.8%; p = 0.4481) the addition of droperidol. Postoperative opioid consumption and numeric rating scale acute pain scores were similar between groups.
CONCLUSIONS
The addition of droperidol to IV-PCA reduced the risk of PONV without increasing opiate consumption or influencing the level of sedation. However, additional prophylactic therapies are needed to prevent late-onset PONV.
Topics: Humans; Antiemetics; Droperidol; Postoperative Nausea and Vomiting; Morphine; Cohort Studies; Retrospective Studies; Analgesia, Patient-Controlled; Propensity Score; Double-Blind Method
PubMed: 37898746
DOI: 10.1186/s12871-023-02319-2 -
The American Journal of Emergency... Jan 2024Gastroparesis is a syndrome of delayed gastric emptying without obstruction. There are high rates of Emergency Department (ED) visits due to gastroparesis, and this...
BACKGROUND/PURPOSE
Gastroparesis is a syndrome of delayed gastric emptying without obstruction. There are high rates of Emergency Department (ED) visits due to gastroparesis, and this chronic disease is difficult to treat which often leads to hospital admissions. This study aimed to evaluate the impact droperidol administration has on opioid therapy, symptom relief, co-administration of antiemetic and prokinetic medications, disposition, cost, and length of stay (LOS) of patients presenting to the ED.
RESULTS
A total of 431 patients were identified and 233 met the inclusion criteria. Droperidol administration reduced the number of patients requiring opioid therapy (108/233 [46%] vs 139/233 [60%], P-value 0.0040), reduced patient-reported pain scales by 4 points, and reduced antiemetic therapy requirement (140/233 [60%] vs 169/233 [73%], P-value 0.0045). No differences were found in terms of ED LOS (Median 6 h [IQR 4-8] vs 5 h [IQR 4-9], P-value 0.3638), hospital LOS (Median 6 h [IQR 4-30 vs 7 h [IQR 4-40], P-value 0.8888), hospital admission rates (67/233 [29%] vs 71/233 [31%], P-value 0.6101), ED cost to the facility (Median $1462 [IQR $1114 - $1986] vs $1481 [IQR $1034 - $2235], P-value 0.0943), or hospital cost (Median $4412 [IQR $2359 - $9826] vs $4672 [IQR $2075 - $9911], P-value 0.3136).
CONCLUSION
In patients with gastroparesis presenting to the ED, droperidol reduced opioid use, improved pain control, and decreased antiemetic use without any differences in MME per dose, length of stay, hospital admission rate, or cost.
Topics: Humans; Droperidol; Antiemetics; Analgesics, Opioid; Gastroparesis; Length of Stay; Emergency Service, Hospital; Pain; Retrospective Studies
PubMed: 37897920
DOI: 10.1016/j.ajem.2023.10.030 -
Journal of Anesthesia Dec 2023Perioperative shivering is common and can occur as a result of hypothermia or changes in the threshold of thermoregulation. Droperidol usage for anesthesia is currently...
PURPOSE
Perioperative shivering is common and can occur as a result of hypothermia or changes in the threshold of thermoregulation. Droperidol usage for anesthesia is currently limited to its sedative and antiemetic effects. We investigated the effects of high and low doses of droperidol on the shivering threshold in rabbits.
METHODS
Forty-two male Japanese white rabbits were anesthetized with isoflurane and randomly assigned to the control, high-dose, or low-dose group. Rabbits in the high-dose group received a 5 mg/kg droperidol bolus followed by continuous infusion at 5 mg/kg/h, those in the low-dose group received a 0.5 mg/kg droperidol bolus, and those in the control group received the same volume of saline as the high-dose group. Body temperature was reduced at a rate of 2-3 °C/h, and the shivering threshold was defined as the subject's core temperature (°C) at the onset of shivering.
RESULTS
The shivering thresholds in the control, high-dose, and low-dose groups were 38.1 °C ± 1.1 °C, 36.7 °C ± 1.2 °C, and 36.9 °C ± 1.0 °C, respectively. The shivering thresholds were significantly lower in the high-dose and low-dose groups than in the control group (P < 0.01). The thresholds were comparable between the high-dose and low-dose groups.
CONCLUSIONS
Droperidol in high and low doses effectively reduced the shivering threshold in rabbits. Droperidol has been used in low doses as an antiemetic. Low doses of droperidol can reduce the incidence of shivering perioperatively and during the induction of therapeutic hypothermia.
Topics: Animals; Rabbits; Male; Shivering; Droperidol; Body Temperature; Isoflurane; Hypothermia
PubMed: 37566231
DOI: 10.1007/s00540-023-03240-1 -
Journal of Molecular Graphics &... Dec 2023The complex nature of Alzheimer's disease (AD) makes it difficult to understand the exact molecular processes leading to neuron death. However, two molecular factors -... (Meta-Analysis)
Meta-Analysis
Ab initio and comparative 3D modeling of FAM222A-encoded protein and target-driven-based virtual screening for the identification of novel therapeutics against Alzheimer's disease.
The complex nature of Alzheimer's disease (AD) makes it difficult to understand the exact molecular processes leading to neuron death. However, two molecular factors - the production of amyloid-beta plaques and tau tangles - are considered to be linked to AD. A genetic marker for brain atrophy, FAM222A, has been identified by the unique cross-phenotype meta-analysis of genetics imaging and the molecular features show an interaction between the protein aggregatin encoded by FAM222A and amyloid beta (Aβ)-peptide (1-42) via its N-terminal Aβ binding domain, thus increasing Aβ aggregation. Function of Aggregatin protein is unclear, and its 3D structure has not been investigated in experimental analysis, so far. Hence, in the present study, first time in literature, 3D models of FAM222A-encoded Aggregatin were systematically constructed by applying diverse homology modeling approaches and they were used as target structures at the virtual screening of FDA-approved drugs and drugs currently under research in clinical trials. Then, the identified hit molecules were chosen for further molecular dynamics (MD) simulations and post-MD analyses. Our integrated ligand-based and protein-driven-based virtual screening results show that Cefpiramide, Diniprofylline, Fostriecin, and Droperidol may target Aggregatin.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Molecular Dynamics Simulation
PubMed: 37552909
DOI: 10.1016/j.jmgm.2023.108575 -
Academic Emergency Medicine : Official... May 2024Adults with cannabis hyperemesis syndrome (CHS) are increasingly presenting to the emergency department (ED), and this systematic review will evaluate the direct... (Review)
Review
BACKGROUND
Adults with cannabis hyperemesis syndrome (CHS) are increasingly presenting to the emergency department (ED), and this systematic review will evaluate the direct evidence on the effectiveness of capsaicin and dopamine antagonists in its clinical management.
METHODS
A bibliographic search was conducted to address the following population-intervention-control-outcome (PICO) question: (P) adults >18 years old with a diagnosis of acute CHS presenting to the ED; (I) dopamine antagonists (e.g., haloperidol, droperidol) and topical capsaicin; (C) usual care or no active comparator; and (O) symptoms improvement/resolution in ED, ED length of stay, admission rate, ED recidivism, need for rescue medication, and adverse events. This systematic review was conducted in accordance with PRISMA reporting recommendations.
RESULTS
From 53 potentially relevant articles, seven articles were included: five observational studies and two randomized controlled trials, including a total of 492 patients. Five of these studies evaluated the efficacy of capsaicin cream (n = 386), and two examined dopamine antagonists (haloperidol, droperidol; n = 106). There was mixed evidence for the efficacy of capsaicin for reducing nausea and emesis. Both studies evaluating dopamine antagonists detected clinical benefit to usual care or no active comparator.
CONCLUSIONS
There is limited direct evidence on the efficacy of dopamine antagonists or capsaicin for treating CHS in the ED. Current evidence is mixed for capsaicin and potentially beneficial for dopamine antagonists. Because of the small number of studies, small number of participants, lack of standardization of treatment administration, and risk of bias of the included studies, methodologically rigorous trials on both types of intervention are needed to directly inform ED management of CHS.
Topics: Humans; Vomiting; Emergency Service, Hospital; Capsaicin; Dopamine Antagonists; Administration, Topical; Adult; Antiemetics; Syndrome; Female; Male; Cannabinoid Hyperemesis Syndrome
PubMed: 37391387
DOI: 10.1111/acem.14770 -
International Immunopharmacology Aug 2023Postoperative cognitive dysfunction (POCD) is a decline in cognitive function affecting the mental health of aged patients after surgery. The pathological mechanisms...
Postoperative cognitive dysfunction (POCD) is a decline in cognitive function affecting the mental health of aged patients after surgery. The pathological mechanisms underlying POCD have not yet been clarified. The overexpression of the P2X4 receptor in the central nervous system (CNS) was reported to be associated with the onset of POCD. Fast green FCF (FGF), a widely used food dye, could decrease the expression of the P2X4 receptor in the CNS. This study aimed to explore whether FGF could prevent POCD via the down-regulation of CNS P2X4 receptor. Exploratory laparotomy under the anesthesia of fentanyl and droperidol was carried to establish an animal model of POCD in 10-12-months-olds mice. FGF significantly attenuated cognitive impairments and down-regulated the expression of the P2X4 receptor induced by surgery in mice. Moreover, the blockade of CNS P2X4 receptor by intrahippocampal injection of 5-BDBD induced cognitive-enhancing effects on POCD mice. In addition, the effects of FGF were abolished by ivermectin, which is a positive allosteric modulator of the P2X4 receptor. FGF also inhibited M1 polarization of microglia cells, decreased the phosphorylation of nuclear factor-κB (NF-κB), and reduced the production of pro-inflammatory cytokines. These results suggested that FGF produced anti-POCD cognitive-enhancing effects via down-regulation of the P2X4 receptor-associated neuroinflammation, providing a support that FGF might be a potential treatment for POCD.
Topics: Mice; Animals; Postoperative Cognitive Complications; Down-Regulation; Receptors, Purinergic P2X4; Cognitive Dysfunction
PubMed: 37301120
DOI: 10.1016/j.intimp.2023.110462 -
Journal of Oral and Maxillofacial... Sep 2023In the fall of 2021, granisetron was approved for postoperative nausea and vomiting (PONV) management in Japan. However, the comparative efficacy of droperidol and...
BACKGROUND
In the fall of 2021, granisetron was approved for postoperative nausea and vomiting (PONV) management in Japan. However, the comparative efficacy of droperidol and granisetron in the field of orthognathic surgery has not been determined.
PURPOSE
We compare the efficacy of droperidol and granisetron for PONV prophylaxis following orthognathic surgery.
STUDY DESIGN, SETTING, SAMPLE
We performed a retrospective cohort study of patients who underwent orthognathic surgery at a single institution from September 2020 to December 2022. Patients who had undergone Le Fort I osteotomy with sagittal split ramus osteotomy or isolated sagittal split ramus osteotomy were included. Patients were divided into three groups; the isolated droperidol (D), isolated granisetron (G), and droperidol with granisetron (DG) groups. General anesthesia was performed using total intravenous anesthesia for all patients; however, droperidol and granisetron were administered at the anesthesiologist's discretion.
PREDICTOR VARIABLE
PONV prophylactic therapy included isolated droperidol, isolated granisetron, and droperidol with granisetron administration.
OUTCOME VARIABLES
Postoperative nausea (PON) and postoperative vomiting (POV) were determined through medical examination within 48 hours following surgery. Secondary outcomes included complications due to droperidol and/or granisetron administration.
COVARIATES
Age, sex, body mass index, Apfel's score, duration of surgery, duration of anesthesia, intraoperative blood loss, and type of surgery.
ANALYSES
Statistical analysis was conducted using Fisher exact test, Mann-Whitney U test with Bonferroni correction for univariate comparison, and modified Poisson regression for comparison of PON and POV prophylactic efficacy for multivariate analyses. P values <.05 were considered statistically significant.
RESULTS
Our study included 218 participants. There were no significant differences in covariates between groups D (n = 111), G (n = 52), and DG (n = 55). No significant difference in PON incidence was observed between groups. However, POV incidence was significantly lower in group DG than group D (relative risk, 0.21; 95% confidence interval, 0.05 to 0.86; P = .03). No significant difference in complication incidence was observed between groups.
CONCLUSIONS AND RELEVANCE
Granisetron was as effective as droperidol for PONV management, while droperidol combined with granisetron was more effective than isolated droperidol for POV management. As compared to the use of each drug separately, their combination was considered safe, with no increase in complication rates.
Topics: Humans; Droperidol; Granisetron; Postoperative Nausea and Vomiting; Retrospective Studies; Antiemetics; Orthognathic Surgery; Vomiting; Double-Blind Method
PubMed: 37277099
DOI: 10.1016/j.joms.2023.05.010 -
Journal of Anesthesia Aug 2023Anesthesia maintenance using propofol and a propofol bolus dose at the end of surgery have been shown to prevent emergence agitation (EA). However, the preventive...
PURPOSE
Anesthesia maintenance using propofol and a propofol bolus dose at the end of surgery have been shown to prevent emergence agitation (EA). However, the preventive effect of subanesthetic propofol infusion during sevoflurane anesthesia on EA remains unknown. We aimed to evaluate the effect of subanesthetic propofol infusion on EA in children.
METHODS
We retrospectively compared the incidences of severe EA requiring pharmacological intervention in children who underwent adenoidectomy, tonsillectomy with or without adenoidectomy, or strabismus surgery between maintenance with sevoflurane alone (sevoflurane group) and maintenance with subanesthetic propofol with sevoflurane (combination group). A multivariable logistic regression model adjusted for confounders was used to assess the association between anesthesia methods and the occurrence of EA. Additionally, we estimated the direct effect of anesthesia methods by a mediation analysis, excluding the indirect effects of intraoperative fentanyl and droperidol administration.
RESULTS
Among 244 eligible patients, 132 and 112 were in the sevoflurane and combination groups, respectively. The crude incidence of EA was significantly lower in the combination group (17.0% [n = 19]) than in the sevoflurane group (33.3% [n = 44]) (P = 0.005). After adjusting for confounders, the incidence of EA was still significantly lower in the combination group (adjusted odds ratio [aOR]: 0.48, 95% confidence interval [CI] 0.25-0.91). The mediation analysis revealed a direct association of anesthesia methods with a lower EA incidence in the combination group (aOR: 0.48, 95% CI 0.24-0.93) than in the sevoflurane group.
CONCLUSION
Subanesthetic propofol infusion may effectively prevent severe EA requiring the administration of opioids or sedatives.
PubMed: 37188963
DOI: 10.1007/s00540-023-03201-8