Effect of low-dose propofol combined with dexamethasone on the prevention of postoperative nausea and vomiting in gynaecological day surgery under remimazolam-based general anesthesia.

BACKGROUND: To observe the effect of low-dose propofol combined with dexamethasone on the prevention of postoperative nausea and vomiting (PONV) in gynaecological day surgery under remimazolam-based general anesthesia. METHODS: A total of 120 patients, aged from 18 to 65 years old, American Society of Anesthesiologists grade I or II, were scheduled to undergo hysteroscopy under total intravenous anesthesia. The patients were divided into 3 groups (n = 40 each): dexamethasone plus saline group (DC group), dexamethasone plus droperidol group (DD group) and dexamethasone plus propofol group (DP group). Dexamethasone 5 mg and flurbiprofen axetil 50 mg were given intravenously before induction of general anesthesia. Anesthesia induction: remimazolam 6 mg/kg/hours was continuously pumped until sleep and slow intravenous injection of alfentanil 20 ug/kg and mivacurium chloride 0.2 mg/kg was given. Anesthesia maintenance: remimazolam 1 mg/kg/hour and alfentanil 40 ug/kg/hours were continuously pumped. After the start of surgery, DC group was given 2 mL saline, DD group was given droperidol 1 mg, and DP group was given propofol 20 mg. Primary outcome: incidence of PONV in the postanesthesia care unit (PACU). Secondary outcome: incidence of PONV in patients within 24 hours after surgery, as well as general patient data, duration of anesthesia, the recovery time of patients, dose of remimazolam and alfentanil, etc. RESULTS: In PACU, patients of group DD and DP showed less PONV than those in group DC (P < .05). Within 24 hours after operation, there was no significant difference in the incidence of PONV among the 3 groups (P > .05), but the incidence of vomiting in DD group and DP group was significantly lower than that in DC group (P < .05). There was no significant difference in general data, anesthesia time, the recovery time of patients and dosage of remimazolam and alfentanil among the 3 groups (P > .05). CONCLUSION: The effect of low-dose propofol combined with dexamethasone to prevent PONV under remimazolam-based general anesthesia was similar to that of droperidol combined with dexamethasone, both of which significantly reduced the incidence of PONV in the PACU compared to dexamethasone alone. However, low-dose propofol combined with dexamethasone had little effect on the incidence of PONV within 24 hours compared to dexamethasone alone and only reduced the incidence of postoperative vomiting in patients.

Prevention of postoperative nausea and vomiting after gynaecological day surgery under remimazolam general anesthesia: a randomized double-blind controlled study.

PURPOSE: To observe the effect of different antiemetic drugs for the prevention of postoperative nausea and vomiting (PONV) after gynaecological day surgery under remimazolam general anesthesia. METHODS: One hundred ninety-two patients were selected for gynaecological day surgery and randomly divided into three groups: droperidol group (DD group), tropisetron group (DT group) and control group (DC group). Flurbiprofen axetil 50 mg and dexamethasone 5 mg were given intravenously before induction of anesthesia, and 2 min later droperidol 1 mg was given intravenously to the DD group, tropisetron 5 mg to the DT group and saline (5 ml) to the DC group. Induction of anesthesia: remimazolam 6 mg/kg/h was continuously infused until sleep, mivacurium 0.2 mg/kg and alfentanil 20ug/kg were slowly pushed, 3 min later intubation was performed to control breathing. Maintenance of anesthesia: 40ug/kg/h of alfentanil, 1 mg/kg/h of remimazolam continuous infusion. After awakening and extubation, the patient was transferred to the PACU. PONV were recorded in the PACU and an electronic questionnaire was pushed 24 h after surgery. RESULTS: The incidence of PONV within the PACU was significantly lower in the DD (14.5%)and DT(26.7%) groups than in the DC(50%) group (p < 0.01), there was no significantly difference between the DT and DD groups. There were no significant difference in the incidence of PONV in 24 h after surgery between the three groups(DD:DT:DC = 44.5%:45.1%:63.8%,p > 0.05). CONCLUSIONS: Droperidol or tropisetron combined with dexamethasone is superior to dexamethasone alone for the prevention of PONV in the PACU after remimazolam combined with alfentanil anesthesia, with no significant difference in the incidence of PONV in 24 h after surgery.

Duloxetine overdose causes sympathomimetic and serotonin toxicity without major complications.

OBJECTIVE: Duloxetine is a commonly used antidepressant that is a serotonin and norepinephrine reuptake inhibitor. We aimed to investigate the frequency and severity of clinical effects following duloxetine overdose. METHODS: We undertook a retrospective review of duloxetine overdoses (>120 mg) admitted to two tertiary toxicology units between March 2007 and May 2021. Demographic information, details of ingestion (dose, co-ingestants), clinical effects, investigations (ECG parameters including QT interval), complications (coma [GCS < 9], serotonin toxicity, seizures and cardiovascular effects), length of stay [LOS] and intensive care unit [ICU] admission were extracted from a clinical database. RESULTS: There were 241 duloxetine overdoses (>120 mg), median age 37 years (interquartile range [IQR]: 25-48 years) and there were 156 females (65%). The median dose was 735 mg (IQR: 405-1200 mg). In 177 patients, other medications were co-ingested, most commonly alcohol, paracetamol, quetiapine, diazepam, ibuprofen, pregabalin and oxycodone. These patients were more likely to be admitted to ICU (12 [7%] vs. none; p = 0.040), develop coma (16 [9%] vs. none; p = 0.008) and hypotension [systolic BP < 90 mmHg] (15 [8%] vs. one; p = 0.076). Sixty four patients ingested duloxetine alone with a median dose of 840 mg (180-4200 mg). The median LOS, in the duloxetine only group, was 13 h (IQR:8.3-18 h), which was significantly shorter than those taking coingestants, 19 h (IQR:12-31 h; p = 0.004). None of these patients were intubated. Six patients developed moderate serotonin toxicity, without complications and one had a single seizure. Tachycardia occurred in 31 patients (48%) and mild hypertension (systolic BP > 140 mmHg) in 29 (45%). One patient had persistent sympathomimetic toxicity, and one had hypotension after droperidol. Two patients of 63 with an ECG recorded had an abnormal QT: one QT 500 ms, HR 46 bpm, which resolved over 3.5 h and a second with tachycardia (QT 360 ms, HR 119 bpm). None of the 64 patients had an arrhythmia. CONCLUSION: Duloxetine overdose most commonly caused sympathomimetic effects and serotonin toxicity, consistent with its pharmacology, and did not result in coma, arrhythmias or intensive care admission, when taken alone in overdose.

Patients treated for acute headache with intranasal droperidol spend less time in the emergency department: A retrospective observational study.

OBJECTIVE: Headache is a common presenting complaint to the ED. Using time from the first provider to discharge as a surrogate for effectiveness, we aimed to determine if intranasal (IN) droperidol is as beneficial as usual treatment for acute headache in the ED. METHODS: There were 1213 consecutive presentations of adults with acute headache over a 42-month period. Electronic records for each event were interrogated, 406 events met pre-determined exclusion criteria. Of the remaining 805 eligible patient events, 139 received IN droperidol, whereas 666 were given usual therapy. RESULTS: There was a 20 min reduction of mean and median ED length of stay (LOS) for the group that got treated with IN droperidol. CONCLUSIONS: IN droperidol reduced LOS in the ED. There are potential cost savings of this effective treatment via this novel route. A prospective multi-centre study of the use of IN droperidol for the treatment of acute headache in the ED is recommended.

Prospective study of haloperidol plus lorazepam versus droperidol plus midazolam for the treatment of acute agitation in the emergency department.

STUDY OBJECTIVES: The objective of this study was to compare the combination of intramuscular (IM) droperidol/midazolam to haloperidol/lorazepam regarding time to sedation in patients with acute undifferentiated agitation in the emergency department (ED). METHODS: This was a prospective, unblinded observational study in the ED of a university teaching hospital. Subjects with acute undifferentiated agitation refractory to verbal de-escalation were assigned to receive a combination of either haloperidol 5 mg/lorazepam 2 mg or droperidol 5 mg/midazolam 5 mg IM. The primary outcome was the proportion of patients adequately sedated at 10 min defined as ED Sedation Assessment Tool (SAT) score of 0 or less. Secondary outcomes included change in ED SAT score at 5, 15, 30, and 60 min, the need for oxygen supplementation, and the need for airway intervention. RESULTS: A total of 86 patients were enrolled in the study, with 43 patients receiving droperidol/midazolam and 43 patients receiving haloperidol/lorazepam. Ten minutes after receiving medication, 51.2% of patients in the droperidol/midazolam group were adequately sedated compared to 7% of patients in the haloperidol/lorazepam group (OR: 14; 95% CI: 3.7, 52.1). Median time to adequate sedation was 10 min for the droperidol/midazolam group and 30 min for the haloperidol/lorazepam group. Eleven patients (25.6%) in the droperidol/midazolam group received oxygen supplementation compared to four patients (9.3%) in the haloperidol/lorazepam group. No study patients experienced extrapyramidal symptoms or required endotracheal intubation. CONCLUSION: Intramuscular droperidol/midazolam was superior to intramuscular haloperidol/lorazepam in achieving adequate sedation at 10 min. Patients in the droperidol/midazolam arm may be more likely to receive oxygen supplementation than those in the haloperidol/lorazepam arm.

Predictive factors of postoperative fentanyl consumption in patients with inflammatory bowel disease: a retrospective cohort study.

BACKGROUND: Patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, might present difficulties in achieving postoperative analgesia. Prior studies have suggested that patients with IBD undergoing major abdominal surgery require higher doses of perioperative opioids than do patients without IBD. Considering patients with IBD potentially require high-dose opioids, identifying those requiring higher opioid doses will allow clinicians to optimize the perioperative opioid dose and avoid insufficient pain management or complications of opioid overdose. Therefore, we conducted this study to identify predictive factors that might influence postoperative opioid consumption in patients with IBD. METHODS: This single-center, historical cohort study reviewed the medical records of all patients admitted to the IBD center of our institution for surgery and who used intravenous fentanyl patient-controlled analgesia (PCA) after open abdominal surgery between June 2013 and April 2017. Ultimately, 179 patients were enrolled in the analysis. Variables expected to influence and/or represent pain, analgesia, inflammation, disease condition, and extent of surgery were selected as potential explanatory variables for predicting postoperative opioid consumption. Multivariable linear regression analysis was used to examine the effect of independent variables on postoperative fentanyl consumption. RESULTS: Of the nine predictive variables selected using the stepwise-selection method, eight were significant. Intraoperative fentanyl consumption, current smoking, ulcerative colitis, administration of biologics during the month before surgery, and the use of supplementary analgesics had a significant increasing effect on postoperative fentanyl consumption, whereas droperidol concentration in the PCA solution, age, and diabetes mellitus had a significant decreasing effect. Preoperative use of opioids was a non-significant variable. The adjusted coefficient of determination was 0.302. CONCLUSIONS: Intraoperative fentanyl consumption, current smoking, ulcerative colitis, administration of biologics during the month before surgery, and the use of supplementary analgesics had a significant increasing effect, whereas droperidol concentration in the PCA solution, age, and diabetes mellitus had a significant decreasing effect on postoperative fentanyl consumption. These factors should be considered when adopting postoperative intravenous fentanyl PCA administration for patients with IBD. TRIAL REGISTRATION: Registry: UMIN Clinical Trials Registry. CLINICAL TRIAL NUMBER: UMIN000031198 . Date of registration: February 8, 2018.

Comparative study between S-(+)-ketamine­midazolam and fentanyl­droperidol in black-tufted marmosets (Callithrix penicillata) / Estudo comparativo entre S-(+)cetamina-midazolam e fentanil-droperidol em saguis-de-tufo-preto (Callithrix penicillata)

Sedative and antinociceptive effects of two anesthetic protocols in black-tufted marmosets were compared in this study. Twenty-six marmosets underwent chemical immobilization for physical examination, blood sampling, tattooing, and microchipping. Animals were randomly treated with S-(+)-ketamine (10 mg/kg) and midazolam (1 mg/kg) (KM) or fentanyl (12.5 µg/kg) and droperidol (625 µg/kg) (FD) given by intramuscular injection. Heart and respiratory rates were recorded. Sedation, antinociception, muscle relaxation, posture, auditory, and visual responses were evaluated using a scoring system. Sedation in KM was achieved faster (p < 0.001) and lasted for a shorter period of time (p = 0.0009). KM was similar to FD in its cardiorespiratory effects, auditory and visual responses. Both protocols promoted adequate sedation to allow manipulation. Animals in KM assumed lateral recumbency while animals in FD maintained a quadrupedal posture during evaluation. FD produced less intense sedation and muscle relaxation but a higher degree of antinociception compared to KM and is suitable for procedures that require analgesia in black-tufted marmosets.(AU)

O presente estudo comparou os efeitos cardiorrespiratórios, sedativos e antinociceptivos de dois protocolos anestésicos em saguis-de-tufo-preto (Callithrix penicillata). Vinte e seis saguis foram submetidos à contenção química para exame físico, coleta de sangue, tatuagem de identificação e microchip. Os animais foram tratados aleatoriamente com a associação de S-(+)-cetamina (10 mg/kg) e midazolam (1 mg/kg) (KM) ou fentanil (12,5 µg/kg) e droperidol (625 µg/kg) (FD), administrados por injeção intramuscular. Foram avaliadas frequência cardíaca, frequência respiratória, sedação, antinocicepção, relaxamento muscular, postura e resposta ao estímulo auditivo e visual. A sedação em KM foi alcançada mais rapidamente (p <0,001) e teve um tempo hábil mais curto (p = 0,0009). KM foi semelhante a FD nos efeitos cardiorrespiratórios, respostas auditivas e visuais. Os dois protocolos promoveram sedação adequada para manipulação. Os animais do grupo KM permaneceram em decúbito lateral durante a avaliação, enquanto os animais em FD mantiveram postura quadrupedal. FD resultou em sedação e relaxamento muscular de menor intensidade, porém com maior escore de antinocicepção em comparação com KM, sendo adequada para procedimentos que requerem analgesia em saguis-de-tufo-preto.(AU)

Emergency medicine updates: Droperidol.

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.

Rapid tranquilization of the agitated patient in the emergency department: A systematic review and network 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.

Impact of extending prevention of postoperative nausea and vomiting for cancer surgical patients in the PACU: a before and after retrospective study.

BACKGROUNDS: Procedures for Postoperative Nausea and Vomiting (PONV) prevention are mostly based on identification of the risk factors before administering antiemetic drugs. The purpose of this study was to evaluate the impact of the extended use of antiemetic on the PONV in the Postanesthetic Care Unit (PACU). METHODS: Two separate 4-year periods (2007...2010, P1, and (2015...2018, P2) were evaluated. During P1, the protocol consisted of dexamethasone and droperidol for patients with a locally adapted high PONV score, followed by ondansetron for rescue in the PACU. For Period 2, dexamethasone (8 mg) and ondansetron (4 mg) were administered in patients under general or regional anesthesia, or sedation longer than 30 minutes, while droperidol (1.25 mg) in rescue was injected in cases of PONV in the PACU. An Anesthesia Information Management System was used to evaluate the intensity score of PONV (1 to 5), putative compliance, sedation, and perioperative opioid consumption upon arrival in the PACU. RESULTS: A total of 27,602 patients were assessed in P1 and 36,100 in P2. The administration of dexamethasone and ondansetron increased several fold (p < 0.0001). The high PONV scores were more improved in P2 than in P1, with scores (3+4+5) for P1 vs. P2, p < 0.0001. Overall, 99.7% of the patients in P2 were asymptomatic at discharge. Morphine consumption decreased from 6.9..1.5 mg in P1 to 3.5 .. 1.5 mg in P2 (p < 0.0001). DISCUSSION: The extension of pharmacological prevention of PONV was associated with a decrease in the intensity of severe PONV. However, uncertainty regarding confounding factors should not be ignored. IRB: n.. 92012/33465.

Low-dose Droperidol Reduces the Amplitude of Transcranial Electrical Motor-evoked Potential: A Randomized, Double-blind, Placebo-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.

Prospective real-time evaluation of the QTc interval variation after low-dose droperidol among emergency department patients.

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.

A Prospective Study of Intramuscular Droperidol or Olanzapine for Acute Agitation in the Emergency Department: A Natural Experiment Owing to Drug Shortages.

STUDY OBJECTIVE: Intramuscular medications are commonly used to treat agitation in the emergency department (ED). The purpose of this study is to compare intramuscular droperidol and olanzapine for treating agitation. METHODS: This was a prospective observational study of ED patients receiving intramuscular droperidol or olanzapine for acute agitation. The treating physician determined the medication and dose; however, over time drug shortages made either olanzapine (July to September 2019) or droperidol (November 2019 to March 2020) unavailable, creating a natural experiment. The primary outcome was time to adequate sedation, assessed by the Altered Mental Status Scale (AMSS), defined as time to AMSS score less than or equal to 0. RESULTS: We analyzed 1,257 patients (median age 42 years; 73% men); 538 received droperidol (median dose 5 mg) and 719 received olanzapine (median dose 10 mg). The majority of patients (1,086; 86%) had agitation owing to alcohol intoxication. Time to adequate sedation was 16 minutes (interquartile range 10 to 30 minutes) for droperidol and 17.5 minutes (interquartile range 10 to 30 minutes) for olanzapine (absolute difference -0.7 minutes; 95% confidence interval -2.1 to 0.5 minutes). Adjusted Cox proportional hazard model analysis revealed no difference between groups in time to sedation (hazard ratio for adequate sedation for droperidol compared with olanzapine 1.12; 95% confidence interval 1.00 to 1.25). Patients receiving olanzapine were more likely to receive additional medications for sedation (droperidol 17%; olanzapine 24%; absolute difference -8% [95% confidence interval -12% to -3%]). We observed no difference between drugs regarding adverse effects except for extrapyramidal adverse effects, which were more common with droperidol (n=6; 1%) than olanzapine (n=1; 0.1%). CONCLUSION: We found no difference in time to adequate sedation between intramuscular droperidol and olanzapine.

Safety and effectiveness of olanzapine and droperidol for chemical restraint for non-consenting adults: a systematic review and meta-analysis.

BACKGROUND: Chemical restraint (CR) is emergency drug management for acute behavioural disturbances in people with mental illness, provided with the aim of rapid calming and de-escalating potentially dangerous situations. AIMS: To describe a systematic review of Randomised Controlled Trials (RCTs) reporting on short-term safety and effectiveness of drugs used for CR, administered to non-consenting adults with mental health conditions, who require emergency management of acute behavioural disturbances. A meta-analysis was conducted of those RCTs with comparable interventions, outcome measures and measurement timeframes. METHOD: Academic databases were searched for RCTs published between 1 January 1996 and 20th April 2020. Relevant RCTs were critically appraised using the 13-item JBI checklist. All RCTs were described, and step-wise filters were applied to identify studies suitable for meta-analysis. For these, forest and funnel plots were constructed, and Q and I2 statistics guided interpretation of pooled findings, tested using MedCalc Version 19.1. RESULTS: Of 23 relevant RCTs, 18 (78.2% total) had excellent methodological quality scores (at least 90%). Eight RCTs were potentially relevant for meta-analysis (six of excellent quality), reporting 20 drug arms in total. Adverse events for 6-36% patients were reported in all 20 drug arms. Four drug arms from two homogenous studies of N = 697 people were meta-analysed. These RCTs tested two antipsychotic drugs (droperidol, olanzapine) delivered intravenously in either 5 mgs or 10 mg doses, with outcomes of time to calm, percentage calm within five or 10 min, and adverse events. There were no significant differences between drug arms for either measure of calm. However, 5 mg olanzapine incurred significantly lower risk of adverse events than 10 mg olanzapine (OR 0.4 (95%CI 0.2-0.8)), although no dose differences were found for droperidol. CONCLUSION: 5 mg intravenous olanzapine is recommended for quick, safe emergency management of people with acute behavioural disturbances associated with mental illness.

Ketamine as a rescue treatment for severe acute behavioural disturbance: A prospective prehospital study.

OBJECTIVE: Rapidly and safely managing severe acute behavioural disturbance (ABD) in the prehospital setting is important for the welfare of both patient and prehospital clinician alike. We investigated the safety and effectiveness of ketamine as rescue sedation in patients with severe ABD. METHODS: This prospective observational study investigated ketamine use by a state ambulance service as rescue sedation for patients with severe ABD who remained agitated following droperidol administration. The primary outcome was the proportion of adverse events (vomiting, hypersalivation, emergence, over-sedation, airway obstruction, laryngospasm, hypoxia, bradypnoea and intubation). Secondary outcomes included time to sedation, requirement for additional sedation and rate of successful sedation. RESULTS: There were 105 presentations (males 69/102 [69%]; median age 31 years (16-83 years). The commonest causes of ABD were illicit drug (39%) and alcohol (33%) intoxication. The median total dose of intramuscular ketamine was 200 mg (interquartile range [IQR] 150-200 mg). There were 64 adverse events in 40 (38%) patients. Four had vomiting, two had hypersalivation, two had emergence, 15 were oversedated, four had hypoxia, three had bradypnoea and 16 were intubated. Sedation was achieved in 103 (98%) patients at a median time post-ketamine of 8 min (IQR 5-13 min). Additional sedation was administered to 41 patients (nine prehospital and 37 within 1 h of arriving to hospital). In 44 (42%) patients, ketamine successfully sedated the patient with no adverse effects and no ongoing sedation requirement. CONCLUSION: The use of ketamine as rescue sedation in prehospital patients with severe ABD is effective. Adverse events are common but can be managed supportively.

Randomized Double-blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department.

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 (ETCO2 ), and pulse oximetry (SpO2 ) 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 ETCO2 consistent with respiratory depression or SpO2  < 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.

Low-dose droperidol suppresses transcranial electrical motor-evoked potential amplitude: a retrospective study.

Low-dose droperidol has been widely used as an antiemetic during and after surgery. Although high-dose droperidol affects motor-evoked potential, the effects of low-dose droperidol on motor-evoked potential amplitude are unclear. The aim of this study was to investigate whether low-dose droperidol affects motor-evoked potential amplitude. We retrospectively reviewed the data of patients who underwent spine surgery under general anesthesia with motor-evoked potential monitoring from February 2016 to 2017. The outcome was the motor-evoked potential amplitude of the bilateral abductor pollicis brevis muscle, tibialis anterior muscle, and abductor hallucis muscle within 1 and 1-2 h after droperidol administration, compared with the baseline motor-evoked potential value. Thirty-four patients were analyzed. The median dose of droperidol was 21 µg/kg. The motor-evoked potential amplitudes of all muscles were significantly reduced after droperidol administration and recovered to baseline values within 2 h. The reduction of all motor-evoked potential amplitudes after droperidol administration was 37-45% of baseline values. There were no significant differences in other drugs administered. There were no serious adverse effects of droperidol administration. Motor-evoked potential amplitude was suppressed by low-dose droperidol. During intraoperative motor-evoked potential monitoring in spine surgery, anesthesiologists should pay careful attention to the timing of administration of droperidol, even at low doses. Based on the results of this study, we are conducting a randomized controlled trial.