Intramuscular Midazolam Research Articles

Some cardiopulmonary effects of capnoperitoneum in anesthetized guinea pigs (Cavia porcellus): spontaneous ventilation versus intubation and mechanical ventilation

ObjectiveTo compare cardiopulmonary variables and blood gas analytes in guinea pigs (Cavia porcellus) during anesthesia with and without abdominal carbon dioxide (CO2) insufflation at intra-abdominal pressures (IAPs) 4 and 6 mmHg, with and without endotracheal intubation. Study designProspective experimental trial. AnimalsA total of six intact female Hartley guinea pigs. MethodsA crossover study with sequence randomization for IAP and intubation status was used. The animals were sedated with intramuscular midazolam (1.5 mg kg–1) and buprenorphine (0.2 mg kg–1) and anesthetized with isoflurane, and an abdominal catheter was inserted for CO2 insufflation. Animals with endotracheal intubation were mechanically ventilated and animals maintained using a facemask breathed spontaneously. After 15 minutes of insufflation, the following variables were obtained at each IAP: pulse rate, respiratory rate, rectal temperature, oxygen saturation, end-tidal CO2 (intubated only), peak inspiratory pressure (intubated only), noninvasive blood pressure and blood gas and electrolyte values, with a rest period of 5 minutes between consecutive IAPs. After 4 weeks, the procedure was repeated with the guinea pigs assigned the opposite intubation status. ResultsIntubated guinea pigs had significantly higher pH and lower partial pressure of CO2 in cranial vena cava blood (PvCO2) than nonintubated guinea pigs. An IAP of 6 mmHg resulted in a significantly higher PvCO2 (65.9 ± 19.0 mmHg; 8.8 ± 2.5 kPa) than at 0 (53.2 ± 17.2 mmHg; 7.1 ± 2.3 kPa) and 4 mmHg (52.6 ± 10.8 mmHg; 7.01 ± 1.4 kPa), mean ± standard deviation, with intubated and nonintubated animals combined. Conclusions and clinical relevanceAlthough the oral anatomy of guinea pigs makes endotracheal intubation difficult, capnoperitoneum during anesthesia induces marked hypercapnia in the absence of mechanical ventilation. An IAP of 4 mmHg should be further evaluated for laparoscopic procedures in guinea pigs because hypercapnia may be less severe than with 6 mmHg.

The IN-MIDAZ study – Intranasal midazolam in aborting seizures – An epilepsy monitoring unit based randomized controlled trial for efficacy

ObjectiveTo compare efficacy and safety of Intranasal and Intramuscular routes of midazolam administration in terminating seizures. MethodThis was an open label Randomized controlled trial (RCT). People with drug resistant epilepsy (DRE) undergoing Video Electroencephalogram (VEEG) monitoring, were randomized in a 1:1 ratio to receive either Intranasal (IN) or Intramuscular (IM) midazolam, for prolonged seizures: longer than 5 min for focal, and longer than 2 min for focal to bilateral tonic-clonic. Outcome assessor was blinded to the allocation arm. Primary outcome was time to electrographic seizure termination after administration of midazolam. All adverse events in both the groups were noted. ResultA total of 1108 seizures were recorded in 130 subjects, of which 110 (65 seizures in 23 subjects in IN group; 45 seizures in 18 subjects in IM group) seizures required midazolam administration and were included in final analysis. Mean time to electrographic seizure termination after midazolam administration was 45.1 ± 23.8 s in the IM group and 90.4 ± 59.0 s in the IN group (p = 0.0014); mean time to clinical seizure termination was 53.9 ± 25.8 s in IM group and 104.3 ± 66.4 s in the IN group (p = 0.002). Local side effects were more in IN group; hypotension as serious adverse event was noted in the IM group. SignificanceThough mean time to electrographic and clinical seizure termination was significantly lesser in Intramuscular group for both adults and pediatric population, it was still under 2 min in the Intranasal midazolam group.IN midazolam is a useful option for terminating seizures.

Comparison of two injectable anaesthetic protocols in Egyptian fruit bats (Rousettus aegyptiacus) undergoing gonadectomy

Egyptian fruit bats have gained increasing interest being a natural reservoir for emerging zoonotic viruses. Anaesthesia is often required to allow safe handling of bats. We aimed to compare the sedative and cardiopulmonary effects of two balanced anaesthetic protocols in bats undergoing gonadectomy. Group DK (n = 10) received intramuscular dexmedetomidine (40 µg/kg) and ketamine (7 mg/kg), whereas group DBM (n = 10) received intramuscular dexmedetomidine (40 µg/kg), butorphanol (0.3 mg/kg) and midazolam (0.3 mg/kg). Induction time and cardiopulmonary parameters were recorded. If anaesthetic plan was inadequate, isoflurane was titrated-to-effect. At the end of surgery venous blood gas analysis was performed and atipamezole or atipamezole-flumazenil was administered for timed and scored recovery. In DBM group heart rate and peripheral oxygen saturation were significantly higher (p = 0.001; p = 0.003 respectively), while respiratory rate was significantly lower (p = 0.001). All bats required isoflurane supplementation with no significant differences between groups. Induction and recovery times showed no significant differences. In group DK a better recovery was scored (p = 0.034). Sodium and chloride were significantly higher in DBM group (p = 0.001; p = 0.002 respectively). Both anaesthetic protocols were comparable and can be recommended for minor procedures in bats.

Optimal Management of Status Epilepticus in Children in the Emergency Setting: A Review of Recent Advances.

Convulsive status epilepticus (CSE) is the most common neurological emergency in children and the second most common neurological emergency in adults. Mortality is low, but morbidity, including neuro-disability, learning difficulties, and a de-novo epilepsy, may be as high as 22%. The longer the duration of CSE, the more difficult it is to terminate, and the greater the risk of morbidity. Convulsive status epilepticus is usually managed using specific national or local algorithms. The first-line treatment is administered when a tonic-clonic or focal motor clonic seizure has lasted five minutes (impending or premonitory CSE). Second-line treatment is administered when the CSE has persisted after two doses of a first-line treatment (established CSE). Randomised clinical trial (RCT) evidence supports the use of benzodiazepines as a first-line treatment of which the most common are buccal or intra-nasal midazolam, rectal diazepam and intravenous lorazepam. Alternative drugs, for which there are considerably less RCT data, are intra-muscular midazolam and intravenous clonazepam. Up until 2019, phenobarbital and phenytoin (or fosphenytoin) were the preferred second-line treatments but with no good supporting RCT evidence. Robust RCT data are now available which has provided important information on second-line treatments, specifically phenytoin (or fosphenytoin), levetiracetam and sodium valproate. Lacosamide is an alternative second-line treatment but with no supporting RCT evidence. Current evidence indicates that first, buccal or intranasal midazolam or intravenous lorazepam are the most effective and the most patient and carer-friendly first-line anti-seizure medications to treat impending or premonitory CSE and second, that there is no difference in efficacy between levetiracetam, phenytoin (or fosphenytoin) or sodium valproate for the treatment of established CSE. Pragmatically, levetiracetam or sodium valproate are preferred to phenytoin (or fosphenytoin) because of their ease of administration and lack of serious adverse side-effects, including potentially fatal cardiac arrhythmias. Sodium valproate must be used with caution in children aged three and under because of the rare risk of hepatotoxicity and particularly if there is an underlying mitochondrial disorder.

Intramuscular Alfaxalone-Butorphanol-Midazolam Compared with Ketamine-Butorphanol- Midazolam in New Zealand White Rabbits.

Rabbits are a common companion animal and research subject and frequently require sedation to facilitate procedures. The objective of this study was to compare the effects of intramuscular butorphanol and midazolam combined with either alfaxalone or ketamine in rabbits. In a complete crossover study, healthy New Zealand white rabbits (n = 9; age, 6 mo) randomly received midazolam (1 mg/kg IM) and butorphanol (1 mg/kg IM) combined with either alfaxalone (2 mg/kg IM; ABM) or ketamine (5 mg/kg IM; KBM). Time to first effects, recumbency, and standing (recovery) were recorded. Every 5 min during recumbency, an investigator who was blind to treatment group collected serial physiologic parameters and sedation scores. At 5 min after rabbits became recumbent, manipulations were performed to mimic 2-view radiography and a cephalic intravenous catheter was placed. At 30 min after drug injection, flumazenil (0.05 mg/kg IM) was administered for reversal. Food consumption and fecal output were measured for 3 d after each study day. Time to standing and duration of recumbency differed significantly between groups. The median (range) of the total sedation score for ABM was 10 (8 to 10) and for KBM was 10 (6 to 10). Sham radiographs were successful in all rabbits in both groups. Physiologic parameters were not significantly different between groups over time. At 24 h after drug treatment, KBM-treated rabbits showed reduced food intake and both groups showed reduced fecal output. Total sedation scores decreased significantly over time in KBM rabbits ( P < 0.001) but not in ABM rabbits (P = 1). The duration of recumbency was significantly longer in ABM rabbits than in KBM rabbits. Both protocols produced sufficient sedation for radiograph acquisition without clinically significant adverse effects.

The Midazolam RAMPART Study Medical Records Project: A Unique Use of Real-World Data in a Complex Collaborative Partnership to Support a New Drug Application

IntroductionThis project aimed to retrospectively obtain, review, and extract key safety data from medical records of participants enrolled in RAMPART, the NIH-supported Rapid Anticonvulsant Medication Prior to ARrival Trial of intramuscular midazolam versus intravenous lorazepam for pre-hospital treatment of status epilepticus, to support a US new drug application (NDA) for intramuscular midazolam.MethodsA collaborative partnership was established between the NDA sponsor, the RAMPART trial lead academic institution, US government agencies, and contract research organizations to retrieve, review, and extract relevant safety data from the medical records of RAMPART participants and summarize those data to include in an NDA submitted to the US Food and Drug Administration (FDA).ResultsKey data in the medical records of 890 RAMPART trial participants (1020 enrollments, including 130 repeat enrollments) were reviewed and extracted into a project database. Safety events occurred in 771 (86.6%) participants, and included additional information not collected in the RAMPART trial. This database also enabled subgroup analyses based on medical history and prior/concurrent medications, building upon previous analyses according to age, sex, and race. No previously unrecognized safety patterns were identified, and no association was observed between efficacy and medical history or medication usage.ConclusionsThe use of unstructured real-world retrospective medical record data can effectively support an NDA submission in place of conducting another interventional clinical trial. This retrospective medical records review and extraction of additional safety data contributed to the FDA approval of intramuscular midazolam for the pre-hospital treatment of status epilepticus in 2018.ClinicalTrials.govNCT00809146.

Real-World Midazolam Use and Outcomes With Out-of-Hospital Treatment of Status Epilepticus in the United States

Guidelines recommend 10-mg intramuscular midazolam as the first-line treatment option for status epilepticus. However, in real-world practice, it is frequently administered intranasally or intravenously and is dosed lower. Therefore, we used conventional and instrumental variable approaches to examine the effectiveness of midazolam in a national out-of-hospital cohort. This retrospective cohort study of adults with status epilepticus used the ESO Data Collaborative research dataset (January 1, 2019, to December 31, 2019). The exposures were the route and dose of midazolam. We performed hierarchical logistic regression and 2-stage least squares regression using agency treatment patterns as an instrument to examine our outcomes, rescue therapy, and ventilatory support. There were 7,634 out-of-hospital encounters from 657 EMS agencies. Midazolam was administered intranasally in 20%, intravenously in 46%, and intramuscularly in 35% of the encounters. Compared with intramuscular administration, intranasal midazolam increased (risk difference [RD], 6.5%; 95% confidence interval [CI], 2.4% to 10.5%) and intravenous midazolam decreased (RD,-11.1%; 95% CI,-14.7% to-7.5%) the risk of rescue therapy. The differences in ventilatory support were not statistically significant (intranasal RD,-1.5%; 95% CI,-3.2% to 0.3%; intravenous RD,-0.3%; 95% CI,-1.9% to 1.2%). Higher doses were associated with a lower risk of rescue therapy (RD,-2.6%; 95% CI,-3.3% to-1.9%) and increased ventilatory support (RD, 0.4%; 95% CI, 0.1% to 0.7%). The instrumental variable analysis yielded similar results, except that dose was not associated with ventilatory support. The route and dose of midazolam affect clinical outcomes. Compared with intramuscular administration, intranasal administration may be less effective and intravenous administration more effective in terminating status epilepticus, although the differences between these and previous results may reflect the nature of real-world data as opposed to randomized data.

Termination of seizures in the paediatric age group, best benzodiazepine and route of administration: A network meta-analysis.

This network meta-analysis aims to compare various benzodiazepines and their route of administration using the data published exclusively in randomized controlled trials (RCTs). Two thousand two hundred sixty-three children presenting with an episode of seizure to ER or to a paramedic where they were administered a benzodiazepine as the first-line treatment were included. All the outcomes were measured for their mean with 95% CI and rank probability. The primary outcome was the number of successful seizure cessation. Secondary outcomes were the time interval between drug administration and seizure cessation, the time interval between patient arrival and seizure cessation and the number of episodes of seizure recurrence after drug administration. For the number of successful cessations, intramuscular midazolam showed the highest mean and best rank probability with a value of .881 (.065) and 57.9%, respectively. For the time of cessation, both intravenous lorazepam (IVL) and intravenous diazepam showed a mean of 3.30 (1.30) with IVL having the highest rank probability of 32%. For total time for cessation, intranasal midazolam showed the best mean and rank probability with a value of 4.3 (1.1) and 55%, respectively. Buccal midazolam showed the lowest mean with a value of .106 (.084) for rate of recurrence. Although there was no significant difference between the treatments, but based on the rank probability, IVL shows more promising results for patients who already have an established intravenous line, and for patients presenting in the ER without an intravenous line, the first line of treatment should be INM as it shows the highest rank probability in total time with second-highest successful cessation rate.

Effect of intramuscular midazolam premedication on patient satisfaction in women undergoing general anaesthesia: a randomised control trial

ObjectiveTo determine the effect of premedication with intramuscular midazolam on patient satisfaction in women undergoing general anaesthesia.Trial design, setting and participantsDouble-blind, parallel randomised control trial at a tertiary care medical...

Feasibility of non-invasive recording of somatosensory evoked potential in pigs

BackgroundNon-invasive measurement of somatosensory-evoked potentials (SEP) in a large animal model is important to translational cognitive research. We sought to develop a methodology for neurophysiological recording via a transcranial electroencephalography (EEG) cap under an effective sedative regimen with dexmedetomidine, midazolam, and butorphanol that will produce sedation instead of anesthesia while not compromising data quality.ResultsPigs received intramuscular dexmedetomidine, midazolam, and butorphanol for SEP assessment with peroneal nerve stimulation. Semi-quantitative sedation assessment was performed after the animal was sufficiently sedated and 30 min later, during the transcranial SEP recording. SEP data were analyzed with commercial software. Binary qualitative analysis of the recording was categorized by an experienced neurophysiologist. All four animals had adequate surface SEP recordings. Animals received 43 [21–47] mcg/kg of dexmedetomidine, 0.3 [0.2–0.3] mg/kg of midazolam, and 0.3 [0.3–0.3] mg/kg of butorphanol IM. All treatments resulted in moderate to deep sedation (Baseline median sedation score 11.5 [11–12]; median score at 30 min: 11.5 [10.5–12]). Heart rate (median [range]) (55 [49–71] beats per minute), respiratory rate (24 [21–30] breaths per minute), and hemoglobin oxygen saturation (99 [98–100]%) and body temperature (37.7 [37.4–37.9] °C) remained within clinically acceptable ranges. There were no undesirable recovery incidents.ConclusionsIn this pilot study, we demonstrate the feasibility of SEP recording via a transcranial EEG cap under an effective sedative regimen in pigs. Our approach will expand the use of a large animal model in neurotranslational research.

Pre-hospital and emergency department treatment of convulsive status epilepticus in adults: an evidence synthesis.

Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded as an emergency condition that requires prompt treatment to avoid hospitalisation and to reduce morbidity and mortality. Rapid pre-hospital first-line treatment of convulsive status epilepticus is currently benzodiazepines, administered either by trained caregivers in the community (e.g. buccal midazolam, rectal diazepam) or by trained health professionals via intramuscular or intravenous routes (e.g. midazolam, lorazepam). There is a lack of clarity about the optimal treatment for convulsive status epilepticus in the pre-hospital setting. To assess the current evidence on the clinical effectiveness and cost-effectiveness of treatments for adults with convulsive status epilepticus in the pre-hospital setting. We searched major electronic databases, including MEDLINE, EMBASE, PsycInfo®, CINAHL, CENTRAL, NHS Economic Evaluation Database, Health Technology Assessment Database, Research Papers in Economics, and the ISPOR Scientific Presentations Database, with no restrictions on publication date or language of publication. Final searches were carried out on 21 July 2020. Systematic review of randomised controlled trials assessing adults with convulsive status epilepticus who received treatment before or on arrival at the emergency department. Eligible treatments were any antiepileptic drugs offered as first-line treatments, regardless of their route of administration. Primary outcomes were seizure cessation, seizure recurrence and adverse events. Two reviewers independently screened all citations identified by the search strategy, retrieved full-text articles, extracted data and assessed the risk of bias of the included trials. Results were described narratively. Four trials (1345 randomised participants, of whom 1234 were adults) assessed the intravenous or intramuscular use of benzodiazepines or other antiepileptic drugs for the pre-hospital treatment of convulsive status epilepticus in adults. Three trials at a low risk of bias showed that benzodiazepines were effective in stopping seizures. In particular, intramuscular midazolam was non-inferior to intravenous lorazepam. The addition of levetiracetam to clonazepam did not show clear advantages over clonazepam alone. One trial at a high risk of bias showed that phenobarbital plus optional phenytoin was more effective in terminating seizures than diazepam plus phenytoin. The median time to seizure cessation from drug administration varied from 1.6 minutes to 15 minutes. The proportion of people with recurrence of seizures ranged from 10.4% to 19.1% in two trials reporting this outcome. Across trials, the rates of respiratory depression among participants receiving active treatments were generally low (from 6.4% to 10.6%). The mortality rate ranged from 2% to 7.6% in active treatment groups and from 6.2% to 15.5% in control groups. Only one study based on retrospective observational data met the criteria for economic evaluation; therefore, it was not possible to draw any robust conclusions on cost-effectiveness. The limited number of identified trials and their differences in terms of treatment comparisons and outcomes hindered any meaningful pooling of data. None of the included trials was conducted in the UK and none assessed the use of buccal midazolam or rectal diazepam. The review of economic evaluations was hampered by lack of suitable data. Both intravenous lorazepam and intravenous diazepam administered by paramedics are more effective than a placebo in the treatments of adults with convulsive status epilepticus, and intramuscular midazolam is non-inferior to intravenous lorazepam. Large well-designed clinical trials are needed to establish which benzodiazepines are more effective and preferable in the pre-hospital setting. This study is registered as PROSPERO CRD42020201953. This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 26, No. 20. See the NIHR Journals Library website for further project information.

Case Analysis of Sprint Interval Training for Adolescents With Severe Mental Illness

Case Analysis of Sprint Interval Training for Adolescents With Severe Mental Illness

Cost-Effectiveness of Midazolam Versus Haloperidol Versus Olanzapine for the Management of Acute Agitation in the Accident and Emergency Department

ObjectivesA multicenter randomized clinical trial in Hong Kong Accident and Emergency (A&E) departments concluded that intramuscular (IM) olanzapine is noninferior to haloperidol and midazolam, in terms of efficacy and safety, for the management of acutely agitated patients in A&E setting. Determining their comparative cost-effectiveness will further provide an economic perspective to inform the choice of sedative in this setting. MethodsThis analysis used data from a randomized clinical trial conducted in Hong Kong A&E departments between December 2014 and September 2019. A within-trial cost-effectiveness analysis comparing the 3 sedatives was conducted, from the A&E perspective and a within-trial time horizon, using a decision-analytic model. Sensitivity analyses were also undertaken. ResultsIn the base-case analysis, median total management costs associated with IM midazolam, haloperidol, and olanzapine were Hong Kong dollar (HKD) 1958.9 (US dollar [USD] 251.1), HKD 2504.5 (USD 321.1), and HKD 2467.6 (USD 316.4), respectively. Agitation management labor cost was the main cost driver, whereas drug costs contributed the least. Midazolam dominated over haloperidol and olanzapine. Probabilistic sensitivity analyses supported that midazolam remains dominant > 95% of the time and revealed no clear difference in the cost-effectiveness of IM olanzapine versus haloperidol (incremental cost-effectiveness ratio 667.16; 95% confidence interval −770.89, 685.90). ConclusionsIM midazolam is the dominant cost-effective treatment for the management of acute agitation in the A&E setting. IM olanzapine could be considered as an alternative to IM haloperidol given that there is no clear difference in cost-effectiveness, and their adverse effect profile should be considered when choosing between them.

Hemodynamic Effects of Different Combinations of Midazolam and Opioids in Healthy Dogs

The purpose of this study was to compare the hemodynamic effects of four different combinations of midazolam and opioids in healthy dogs. Twenty-four healthy dogs were divided in four groups (n = 6) using intramuscular midazolam 0.3 mg/kg and morphine 0.3 mg/kg (GMOR), methadone 0.3 mg/kg (GMET), butorphanol 0.2 mg/kg (GBUT) or fentanyl 5 ug/kg (GFEN). Cardiovascular variables were recorded before (TB) and 20 minutes following drug administration (T20) and comprised arterial blood pressure, heart rate and cardiac index. Subsequently, left ventricular work index and total peripheral resistance index were calculated using the previous variables. At the end of the study, data were compared using analysis of variance followed by Tukey test and Friedman followed by Dunn test, all under 5% significance. No differences were found on cardiovascular variables at all times among the groups, which indicates that all combinations provide hemodynamic stability for clinical sedation of healthy dogs. However, a few animals showed paradoxical excitation in GBUT. In conclusion, the association of midazolam with morphine, methadone, butorphanol or fentanyl provides cardiovascular stability and can be used to sedate dogs undergoing cardiovascular examination, although caution is warranted with the use of midazolam with butorphanol due to possible paradoxical excitation.

Time is Brain

Status epilepticus (SE) is a serious complication of epilepsy that warrants both rapid and appropriate emergency management for better outcomes in terms of mortality and morbidity. The initial management of SE in emergency department (ED) involves a rapid neurological assessment and initiation of supportive therapy. Benzodiazepines are the recommended first-line treatment based on high-quality evidence, among them intramuscular (IM) midazolam IM was found to be as effective as intravenous lorazepam. However, it is important to understand that speedy drug delivery and adequate initial dose are of prime importance than selection of drug. Recent evidence shows all three second-line drugs, namely, valproate, fosphenytoin, and levetiracetam are alike in cessation of SE with similar incidence of adverse events. In refractory SE, the therapeutic options include the use of bolus dose followed by infusion of propofol, midazolam, ketamine, lacosamide, and phenobarbital. Magnesium sulfate is safe and superior in the management of eclamptic SE prompt and appropriate management in ED is the key to early cessation of SE, leading to better outcomes.

Rapid Agitation Control With Ketamine in the Emergency Department: A Blinded, Randomized Controlled Trial

We hypothesized that the use of intramuscular ketamine would result in a clinically relevant shorter time to target sedation. We conducted a randomized clinical trial comparing the rapidity of onset, level of sedation, and adverse effect profile of ketamine compared to a combination of midazolam and haloperidol for behavioral control of emergency department patients with severe psychomotor agitation. We included patients with severe psychomotor agitation measured by a Richmond Agitation Score (RASS) ≥+3. Patients in the ketamine group were treated with a 5 mg/kg intramuscular injection. Patients in the midazolam and haloperidol group were treated with a single intramuscular injection of 5 mg midazolam and 5 mg haloperidol. The primary outcome was the time, in minutes, from study medication administration to adequate sedation, defined as RASS ≤-1. Secondary outcomes included the need for rescue medications and serious adverse events. Between June 30, 2018, and March 13, 2020, we screened 308 patients and enrolled 80. The median time to sedation was 14.7 minutes for midazolam and haloperidol versus 5.8 minutes for ketamine (difference 8.8 minutes [95% confidence interval (CI) 3.0 to 14.5]). Adjusted Cox proportional model analysis favored the ketamine arm (hazard ratio 2.43, 95% CI 1.43 to 4.12). Five (12.5%) patients in the ketamine arm and 2 (5.0%) patients in the midazolam and haloperidol arm experienced serious adverse events (difference 7.5% [95% CI -4.8% to 19.8%]). In ED patients with severe agitation, intramuscular ketamine provided significantly shorter time to adequate sedation than a combination of intramuscular midazolam and haloperidol.

Echocardiographic Assessment of Healthy Midazolam/Butorphanol or Midazolam/Morphine-Sedated Dogs

The purpose of this study was to assess the effects of midazolam combined with morphine or butorphanol on echocardiographic variables of healthy dogs. Twenty-four dogs of various breeds aged 34.33 ± 23.41 months and weighing 8.1 ± 4.7 kg were enrolled in the study. Subjects were randomly allocated in one of two experimental groups of sedation with intramuscular midazolam (0.3 mg/kg) combined with butorphanol (0.2 mg/kg) (GB, n = 12) or morphine (0.3 mg/kg) (GM, n = 12). Transthoracic echocardiographic examinations comprised B-Mode, M-Mode, spectral Doppler and pulsed tissue Doppler assessment. Data were recorded before sedation (TB) and 20 minutes following intramuscular administration of either sedation protocol (TS). Data were analyzed using repeated measures ANOVA followed by Tukey's posthoc test. Shortening fraction, ejection fraction, left ventricular diameter and volume did not differ among groups and time points. The A and E′ waves were decreased in GM at TS compared to TB. Isovolumic relaxation time, Ae/Ao ratio, aortic and pulmonary flows and S′ wave did not differ among time points and groups. These sedation protocols did not cause clinically relevant changes in echocardiographic variables, therefore can be used for sedation of uncooperative dogs during echocardiographic evaluation.

A retrospective study on the safety and effectiveness of olanzapine versus midazolam for pre-hospital management of excited delirium syndrome

Objective: To evaluate the safety and effectiveness of olanzapine compared to midazolam for the pre-hospital management of excited delirium syndrome. Methods: A retrospective review of patients who were treated by ambulance crew for excited delirium syndrome from 2016 to 2019 was performed. The drug of choice was given per Fire Service Department’s paramedic protocol (intramuscular midazolam January 2016 to October 2018 and intramuscular olanzapine October 2018 to December 2019). The primary outcome was the proportion of patients experienced at least one adverse event. The secondary outcome was the successful sedation rate. Results: A total of 201 patients were included in the study. Ninety-nine patients had pre-hospital midazolam and 102 received olanzapine. Thirty-one patients experienced adverse event after arrival to A&amp;E, including a drop of Glasgow Coma Scale score to below 8 (90%), hypotension (6%), and airway obstruction (3%): 17 (17% patients; 1 airway obstruction and 16 Glasgow Coma Scale score below 8) in midazolam group and 14 (14% patients; 2 hypotension and 12 Glasgow Coma Scale score below 8) in olanzapine group (p = 0.41). Sixty-eight patients (69%) in midazolam group achieved successful sedation, compared with 79 (77%) in olanzapine group (p = 0.20). More adverse events were seen with midazolam than olanzapine in alcohol intoxication subgroup with statistical significance (12 vs 2, p = 0.03). Conclusion: Both midazolam and olanzapine can achieve a satisfactory success rate of sedation. More adverse events are associated with midazolam use in patients with acute alcohol intoxication, especially over-sedation and airway compromise. Olanzapine would be a safer choice in the pre-hospital setting where the resource is limited, and differentiation of underlying causes is not always possible.

The Effectiveness of Intranasal Midazolam for the Treatment of Prehospital Pediatric Seizures: A Non-inferiority Study

Background: Intranasal (IN) midazolam allows for rapid, painless treatment of pediatric seizures in the prehospital setting and may be a preferred administration route if determined to be non-inferior to intravenous (IV) or intramuscular (IM) routes. We sought to evaluate the effectiveness of IN midazolam for terminating prehospital pediatric seizures compared to midazolam administered by alternate routes. Methods: We performed a retrospective, non-inferiority analysis using data from a regional Emergency Medical Services (EMS) database. We included pediatric patients ≤ 14 years treated with midazolam (0.1 mg/kg) by EMS for non-traumatic seizures. The primary outcome was the proportion of patients requiring redosing of midazolam after initial treatment with IN midazolam compared to those that received IV or IM midazolam. We established a priori a risk difference of 6.5% as the non-inferiority margin. Results: We evaluated outcomes from 2,034 patients (median age 6 years [interquartile range 3 − 10 years], 55% male). Initial administration routes were 461 (23%) IN, 547 (27%) IM, 1024 (50%) IV, and 2 (0.1%) intraosseous (IO). Midazolam redosing occurred in 116 patients (25%) who received IN midazolam versus 222 patients (14%) treated initially with midazolam via alternate routes (risk difference 11% [95%CI 7 − 15%]). The age-adjusted odds ratio for redosing midazolam after intranasal administration compared to alternate route administration was 2.0 (95% CI 1.6 − 2.6). Conclusion: Prehospital treatment of pediatric seizure with intranasal midazolam was associated with increased frequency of redosing compared to midazolam administered by other routes, suggesting that 0.1 mg/kg is a subtherapeutic dose for intranasal midazolam administration.

Intramuscular midazolam, olanzapine, or haloperidol for the management of acute agitation: A multi-centre, double-blind, randomised clinical trial.

BackgroundThe safety and effectiveness of intramuscular olanzapine or haloperidol compared to midazolam as the initial pharmacological treatment for acute agitation in emergency departments (EDs) has not been evaluated.MethodsA pragmatic, randomised, double-blind, active-controlled trial was conducted from December 2014 to September 2019, in six Hong Kong EDs. Patients (aged 18–75 years) with undifferentiated acute agitation requiring parenteral sedation were randomised to 5 mg intramuscular midazolam (n = 56), olanzapine (n = 54), or haloperidol (n = 57). Primary outcomes were time to adequate sedation and proportion of patients who achieved adequate sedation at each follow-up interval. Sedation levels were measured on a 6-level validated scale (ClinicalTrials.gov Identifier: NCT02380118).FindingsOf 206 patients randomised, 167 (mean age, 42 years; 98 [58·7%] male) were analysed. Median time to sedation for IM midazolam, olanzapine, and haloperidol was 8·5 (IQR 8·0), 11·5 (IQR 30·0), and 23·0 (IQR 21·0) min, respectively. At 60 min, similar proportions of patients were adequately sedated (98%, 87%, and 97%). There were statistically significant differences for time to sedation with midazolam compared to olanzapine (p = 0·03) and haloperidol (p = 0·002). Adverse event rates were similar across the three arms. Dystonia (n = 1) and cardiac arrest (n = 1) were reported in the haloperidol group.InterpretationMidazolam resulted in faster sedation in patients with undifferentiated agitation in the emergency setting compared to olanzapine and haloperidol. Midazolam and olanzapine are preferred over haloperidol's slower time to sedation and potential for cardiovascular and extrapyramidal side effects.FundingResearch Grants Council, Hong Kong.