Total Dose Of Benzodiazepines Research Articles

Morbidity Associated with Deviation from Pediatric Status Epilepticus Guidelines

Treatment guidelines for the management of pediatric status epilepticus (PSE) are often institution-specific. We aim to characterize deviation from our hospital-based PSE treatment guidelines, the total dosage of benzodiazepines administered, and the need for intubation. The study population included all patients with an ICD −10 code for PSE who required admission to the Pediatric Intensive Care Unit (PICU) from April 2019 to April 2022. There were 66 PICU admissions. All patients with concern for PSE and altered mental status are admitted to the PICU. The cohort was divided between those treated according to the PSE protocol (benzodiazepine dose (0.05 mg/kg- 0.2 mg/kg) versus those who had low dose (≤0.05 mg/kg) and high-dose benzodiazepine (> 0.2 mg/kg) totals. The dosage was calculated as the total dose of benzodiazepines received pre-hospital and in the ED before intubation or transport. Forty-one (62 %) of patients received high-dose benzodiazepines (median 0.34 mg/kg [IQR 0.29–0.56], 19 (29 %) received recommended-dose benzodiazepines (median 0.13 mg/kg [IQR 0.09,0.15] and 6 (9 %) received low-dose (median 0.05 mg/kg [IQR 0.03,0.05]. The high-dose group was 15.9 (95 % CI = 3.7, 99.9) times more likely to be intubated controlling for the location of care (tertiary versus community hospital), and the age of the patient. The recommended-dose and low-dose groups required intubation with much less frequency.

Impact of an alcohol withdrawal screening and treatment protocol for hospitalized patients

IntroductionAlcohol Withdrawal Syndrome (AWS) is a potentially life-threatening complication of alcohol use disorder (AUD) that can be challenging to recognize in hospitalized patients. Our institution implemented universal AUD screening for all patients admitted to a non-critical care venue using the Prediction of Alcohol Withdrawal Severity Scale (PAWSS). At risk patients were then further assessed, utilizing the Glasgow Modified Alcohol Withdrawal Scale (GMAWS), and medicated according to a predetermined protocol. This study sought to determine whether this protocol decreased hospital length of stay, lowered the total benzodiazepine dose administered, and decreased adverse events attributable to AWS. MethodsThis retrospective cohort study was conducted over a 6-year period from 2014 to 2020. The study included patients with an ICD-10 code diagnosis of AWS and subsequently divided them into two groups: pre- and post-protocol introduction. Outcome measures were compared pre- versus post-protocol introduction. ResultsThere were 181 patient encounters pre- and 265 patient encounters post-protocol. There was no statistically significant difference in median length of stay between the two groups (2.956 days pre and 3.250 days post-protocol, p = 0.058). Post-protocol, there was a statistically significant reduction in median total benzodiazepine dose (13.5 mg and 9 mg lorazepam equivalents pre- and post-protocol, p < 0.001) and in occurrence of delirium tremens (7.7 % pre and 2.3 % post-protocol, p = 0.006). ConclusionProtocol implementation did not reduce length of stay in patients with AUD but was associated with a significant reduction in total benzodiazepine dose and, when adjusted, a non-statistically significant decrease in progression to delirium tremens in hospitalized patients, after applying Bonferroni adjustment.

33. Ceftriaxone Administration for Concomitant Infection During Alcohol Withdrawal is Associated With Lower Total Benzodiazepine Dose

33. Ceftriaxone Administration for Concomitant Infection During Alcohol Withdrawal is Associated With Lower Total Benzodiazepine Dose

Effect of Phenobarbital-Based Alcohol Withdrawal Protocol on Provider Practice and Patient Outcomes—A Quality Improvement Study

Introduction: Alcohol is the most common substance use disorder in the United States. Despite this prevalence, there remains significant heterogeneity in medical management of alcohol withdrawal syndrome (AWS). While the 2020 American Society of Addition Medicine continues to recommend the use of benzodiazepines as first-line therapy for AWS, there is increasing use of phenobarbital in patients at high risk of severe AWS. Despite phenobarbital’s favorable pharmacologic profile, historically, clinical utilization on general medicine services has been low and often restricted. In this project, we have examined practice patterns and associated clinical outcomes in adult patients experiencing AWS on the general medicine service pre and post implementation of a phenobarbital-based protocol for the treatment of severe AWS at our institution. Methods: This quality improvement study evaluated changes in management of AWS on general medicine units associated with implementation of a phenobarbital-based protocol and order set in the electronic medical record (EMR). Our primary outcome measures were receipt of a phenobarbital loading dose, concomitant benzodiazepine administration, and total benzodiazepine dose. Safety outcomes were also explored to assess clinical impacts of this protocol implementation. The project was determined “not research” by our Institutional Review Board. Results: Phenobarbital-protocol implementation was associated with increased frequency of receiving a phenobarbital loading dose (49.5% vs 9.4%; P &lt; .001), decreased use of concomitant benzodiazepine/phenobarbital (4.3% vs 28.9%; P &lt; .001), and decreased total benzodiazepine dose (7.8 vs 15.5 mg; P &lt; .001). Regarding safety, there was no significant pre/post difference in the rate of ICU transfer, but among those transferred there was a trend toward decreased mechanical ventilation rate (100% vs 28.6%; P = .051), and a significantly reduced ICU length of stay (median 11 vs 3 days; P = .04). There were no pre/post differences in seizures, delirium or use of adjunct medications. Conclusions: This quality improvement study demonstrates a marked change in provider prescribing practices for treating AWS after implementation of an institutional phenobarbital-based protocol. We observed no difference in overall clinical outcomes after protocol implementation, although a larger follow-up study is needed to confirm this and to further explore the shorter ICU length of stay for patients with AWS postimplementation.

Evaluation of phenobarbital dosing strategies for hospitalized patients with alcohol withdrawal syndrome

ObjectiveAlcohol remains the fourth‑leading preventable cause of death in the U.S. The objective of this study was to compare the incidence of phenobarbital (PHB)-resistant withdrawal and determine risk factors for PHB-resistant alcohol withdrawal syndrome (AWS). MethodsThis retrospective cohort study included adults admitted to an academic center with AWS who received PHB as part of an institution-specific treatment protocol. The primary outcome was incidence of AWS resistant to initial protocolized PHB load across two cohorts (standard-dose, 10 mg/kg vs. low-dose, 6 mg/kg). ResultsAmong 176 included patients, there was no difference in the incidence of PHB-resistant AWS based on initial PHB load [low-dose load, 21 (18.3%) vs. standard-dose load, 12 (19.7%), p = 0.82]. There were also no differences in observed PHB-related ADEs between the groups. Total benzodiazepine dose received (mg) in the 24 h prior to initial PHB load was the only risk factor significantly associated with AWS resistant to initial protocolized PHB load [adjusted OR 1.79 (95% CI 1.24, 2.60)]. PHB-resistant withdrawal occurred in 33 (18.8%) patients with a median cumulative PHB dose of approximately 20 mg/kg during hospitalization. Conclusion(s)There were no differences in the incidence of PHB-resistant AWS or PHB-related ADEs based on initial PHB loading dose.

Symptoms-triggered approach versus fixed-scheduled approach of benzodiazepines for management of alcohol withdrawal syndrome: Non-randomized controlled trial.

Alcohol withdrawal syndrome, if untreated, can lead to potentially life-threatening complications. Benzodiazepines are the drugs of choice for the treatment of alcohol withdrawal syndrome. We aimed to compare the symptoms-triggered approach and fixed-dose approach of benzodiazepine administration for treatment of alcohol withdrawal syndrome in regard to the health care utilization measured by the total dose of benzodiazepines, length of hospital stays, and 90-day readmissions rate. A single-center prospective non-randomized controlled trial included all patients diagnosed with alcohol withdrawal syndrome. The group of patients admitted between October 1, 2019, and September 30, 2020, were treated with the fixed-scheduled approach (n=150), while all patients admitted between November 1, 2020, to October 31, 2021, were treated with the symptoms-trigger approach (n=50). The fixed-dose approach group showed a significant higher 90-day readmissions rate (HR: 2.61; 95% CI=1.18, 6.84; p=0.01). Kaplan-Meier survival analysis showed a significantly shorter duration to the first readmission in the fixed-scheduled approach group (HR: 2.3; 95% CI=5.6, 1.16; p=0.02). The symptoms-triggered approach group required a significantly lower dose of diazepam (40mg vs. 10mg; p<0.01) and a higher dose of thiamine (800mg vs. 600mg; p<0.01). Length of hospital stay was significantly increased in the symptoms-triggered approach group (3.9 vs. 2.2 days; p<0.01). The use of a symptoms-triggered approach to treat alcohol withdrawal syndrome was associated with a lower 90-day readmission rate, prolonged period to the first readmission, and reduced total dose of benzodiazepines, but longer length of hospital stays. The symptoms-triggered approach is safe, cost-effective, and associated with reduced alcohol dependence relapse.

Assessing the revised Clinical Institute Withdrawal for Alcohol Scale use at Stikland Hospital.

Alcohol use disorder (AUD) is a major public health concern in South Africa (SA). Abrupt cessation or reduction of alcohol intake in chronic users can result in withdrawal symptoms. Benzodiazepines are the treatment of choice but need to be used cautiously in patients with a lifetime history of substance abuse given their highly addictive potential. Symptom-triggered prescription of benzodiazepines during alcohol withdrawal using the Revised Clinical Institute Withdrawal for Alcohol Scale (CIWA-Ar) has been associated with improved safety and reduced benzodiazepines use. To investigate if implementation of the CIWA-Ar during alcohol detoxification impacted the dose of benzodiazepines used and withdrawal-related outcomes. Alcohol rehabilitation unit (ARU) at Stikland Psychiatric Hospital. A retrospective cohort study of 135 admissions over a six-month period comparing two groups: before (2015) and after (2017) the implementation of the CIWA-Ar. The study noted no differences in sociodemographic and alcohol-associated variables between the two groups, and there were no recorded complications in either group. The 2017 group had a lower percentage of patients that required benzodiazepines (33.8% vs. 51.4%, p = 0.04) and a lower median total amount of benzodiazepines used during alcohol withdrawal (0 mg vs. 5 mg, p = 0.01). The CIWA-Ar rating scale was an effective alternative to prescribing benzodiazepines pro re nata and decreased the total dose of benzodiazepines used during alcohol withdrawal. The use of a symptom triggered regime, like the CIWA-Ar rating scale, during withdrawal can be implemented safely in a SA treatment setting for patients with low-risk AUD.

Post-operative sleep and activity patterns in critically ill children after cardiac surgery

BackgroundChildren with congenital heart disease often have medical and surgical complexity and prolonged and complicated recovery time in the intensive care unit. Limited data are published describing sleep duration, timing, and quality in this population. ObjectivesThis study was performed to describe sleep and activity patterns of children with congenital heart disease in the immediate post-operative period. MethodsThis was a secondary analysis of an observational trial of children (0-18 years) who underwent cardiac surgery and had accelerometer data. The primary outcome was the daytime activity ratio estimate (DARE), defined as the proportion of activity that occurred during the daytime hours. Secondary outcomes were sleep quality, including sleep fragmentation index and sleep duration. ResultsIn total, 130 subjects with 794 hospital days of sleep data were included. Median age was 2.9 years (IQR 0.6-9.9). 83 (63.8%) were males, and 51 (39%) had cyanotic lesions. 35 subjects (26.9%) underwent single ventricle repairs. Average nighttime activity levels were higher than normal in all subjects with an average DARE of 61.1% (±5), normal 75%. Variables independently associated with DARE were total daily sleep time (p=0.005) and total benzodiazepine dose in mcg/kg (p=0.006). Almost half of the subjects had inadequate total sleep time (60, 46%). There was a significant decrease in total sleep time and proportion of subjects with adequate sleep duration in the lower age categories. For every year increase in age, the odds of adequate sleep increased by 27%, p<0.001. ConclusionChildren post cardiac surgery have higher than normal levels of nighttime activity and almost half do not meet the recommended daily hours of sleep. Infants under 1 year of age may be at a higher risk of inadequate sleep. Exposure to benzodiazepines may also affect the balance between daytime and nighttime sleep patterns after cardiac surgery.

Study: Use symptoms for benzo dosing in alcohol withdrawal

Alcohol withdrawal symptoms are traditionally treated by benzodiazepines, often using a fixed‐dose protocol. A new study has found that using a symptoms‐triggered approach resulted in a lower rate of readmissions within 90 days and a reduced total dose of benzodiazepines. The study found that using a symptoms‐triggered approach does result in a longer length of hospital stay, but that this pays off for the patient and the payer in the long run. Using a symptoms‐triggered approach results in a reduced relapse to alcohol dependence, the study found.

Pediatric Ventilation Liberation: Bundled Extubation Readiness and Analgosedation Pathways Decrease Mechanical Ventilation Duration and Benzodiazepine Exposure.

Recent studies reported that children on mechanical ventilation who were managed with an analgosedation approach and standardized extubation readiness testing experienced better outcomes, including decreased delirium and invasive mechanical ventilation duration. This was a quality improvement project in a 24-bed pediatric ICU within a single center, including subjects ≤ 18 years old who required invasive mechanical ventilation via an oral or nasal endotracheal tube. The aim was to decrease the invasive mechanical ventilation duration for all the subjects by 25% within 9 months through the development and implementation of bundled benzodiazepine-sparing analgosedation and extubation readiness testing clinical pathways. In the pre-implementation cohort, there were 274 encounters, with 253 (92.3%) that met inclusion for ending in an extubation attempt. In the implementation cohort, there were 367 encounters with 332 (90.5%) that ended in an extubation attempt. The mean invasive mechanical ventilation duration decreased by 23% (Pre 3.95 d vs Post 3.1 d; P = .039) after the implementation without a change in the mean pediatric ICU length of stay (Pre 7.5 d vs Post 6.5 d; P = .42). No difference in unplanned extubation (P > .99) or extubation failure rates (P = .67) were demonstrated. Sedation levels as evaluated by the mean State Behavioral Scale were similar (Pre -1.0 vs Post -1.1; P = .09). The median total benzodiazepine dose administered decreased by 75% (Pre 0.4 vs Post 0.1 mg/kg/ventilated day; P < .001). No difference in narcotic withdrawal (Pre 17.8% vs Post 16.4%; P = .65) or with delirium treatment (Pre 5.5% vs Post 8.7%; P = .14) was demonstrated. A multidisciplinary, bundled benzodiazepine-sparing analgosedation and extubation readiness testing approach resulted in a reduction in mechanical ventilation duration and benzodiazepine exposure without impacting key balancing measures. External validity needs to be evaluated in similar centers and consensus on best practices developed.

A multifaceted quality improvement intervention to improve management of alcohol withdrawal on a general medicine ward: impact on benzodiazepine use

Objective: To measure the effects of a quality improvement intervention on length of stay and benzodiazepine use among patients admitted for alcohol use disorder. Methods: This retrospective cohort study was performed at the Salt Lake City Veterans Affairs Medical Center. Patients 18 years and older admitted to a general medical ward with a diagnosis of alcohol related disorders who were treated for alcohol withdrawal were included. The baseline cohort included patients admitted over 12 months. The post-intervention cohort included patients admitted over 12 months. Primary outcomes were total benzodiazepine dose and length of stay. Secondary outcomes included episodes of delirium tremens and seizures. Results: Total benzodiazepine dose decreased significantly over the intervention period. Length of stay also decreased. No episodes of delirium tremens or seizures were observed. Conclusions: A quality improvement intervention directed at general medicine inpatients admitted for alcohol withdrawal was associated with reductions in total benzodiazepine administration and length of stay.

Association of neurocognitive functioning with sleep stage dissociation and REM sleep instability in medicated patients with schizophrenia

Many patients with schizophrenia present with impaired cognitive functioning and sleep disturbances. Dissociated stages of sleep represent instability within distinct sleep regulatory cerebral networks. Previous studies found increased rates of rapid eye movement (REM) sleep abnormalities in patients with schizophrenia and a positive association with psychopathology. In this study, we examined if sleep stage dissociation and REM sleep instability was associated with neurocognitive functioning in a sample of medicated patients with schizophrenia. The analyses were performed on 31 baseline polysomnographic recordings as well as baseline data on neurocognitive performance. Regression models were built with the cognitive composite score as primary dependent variable and measures of sleep stage dissociation, including REM sleep without atonia (RSWA), REM sleep without eye movements, non-REM sleep with eye movements, REM sleep percentage in REM periods and REM sleep stability as independent variables. Analyses were adjusted for age, gender, total antipsychotic dose, total benzodiazepine dose, and symptom severity. After correction for multiple testing, we found that the neurocognitive composite score was inversely associated with the degree of RSWA. Exploratory analyses with the cognitive sub scores as dependent variables showed that RSWA was associated with cognitive performance across several sub domains. Dissociated sleep stages, specifically the RSWA feature, might represent a new treatment target for improving cognitive impairment in patients with schizophrenia.

First-line medication dosing in pediatric refractory status epilepticus.

To identify factors associated with low benzodiazepine (BZD) dosing in patients with refractory status epilepticus (RSE) and to assess the impact of BZD treatment variability on seizure cessation. This was a retrospective study with prospectively collected data of children with convulsive RSE admitted between June 2011 and January 2019. We analyzed the initial and total BZD dose within 10 minutes of treatment initiation. We used logistic regression modeling to evaluate predictors of low BZD dosing and multivariate Cox regression analysis to assess the impact of low BZD dosing on time to seizure cessation. We included 289 patients (55.7% male) with a median age of 4.3 (1.3-9.5) years. BZDs were the initial medication in 278 (96.2%). Of those, 161 patients (57.9%) received a low initial dose. Low initial BZD doses occurred in both out-of-hospital (57 of 106; 53.8%) and in-hospital (104 of 172; 60.5%) settings. One hundred three patients (37.1%) received low total BZD dose. Male sex (odds ratio [OR] 2, 95% confidence interval [CI] 1.18-3.49; p = 0.012), older age (OR 1.1, 95% CI 1.05-1.17; p < 0.001), no prior diagnosis of epilepsy (OR 2.1, 95% CI 1.23-3.69; p = 0.008), and delayed BZD treatment (OR 2.2, 95% CI 1.24-3.94; p = 0.007) were associated with low total BZD dose. Patients who received low total BZD dosing were less likely to achieve seizure cessation (hazard ratio 0.7, 95% CI 0.57-0.95). BZD doses were lower than recommended in both out-of-hospital and in-hospital settings. Factors associated with low total BZD dose included male sex, older age, no prior epilepsy diagnosis, and delayed BZD treatment. Low total BZD dosing was associated with decreased likelihood of Seizure cessation. This study provides Class III evidence that patients with RSE who present with male sex, older age, no prior diagnosis of epilepsy, and delayed BZD treatment are more likely to receive low total BZD doses. This study provides Class III evidence that in pediatric RSE low total BZD dose decreases the likelihood of seizure cessation.

Symptom-Triggered Therapy for Alcohol Withdrawal Syndrome: a Systematic Review and Meta-analysis of Randomized Controlled Trials.

Benzodiazepines are the standard medication class for treating alcohol withdrawal. Guidelines recommend dosing based on objectively measured symptoms (symptom-triggered therapy) rather than fixed dose regimens. However, the superiority of symptom-triggered therapy has been questioned, and concerns have been raised about its inappropriate use and safety. We aimed to assess whether symptom-triggered therapy is superior to fixed dose schedules in terms of mortality, delirium, seizures, total benzodiazepine dose, and duration of therapy. A systematic literature search using Medline, Embase, and the Cochrane Registry through February 2018 was conducted for randomized controlled trials of patients with alcohol withdrawal syndrome comparing fixed dose benzodiazepine schedules to symptom-triggered therapy. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Outcomes were pooled using random effects meta-analysis. Heterogeneity was estimated using the I2 statistic. Strength of evidence was assessed using methods outlined by the Agency for Healthcare Research and Quality. Six studies involving 664 patients were included. There were no deaths and only one seizure in each group. Four studies reported delirium, which occurred in 4 out of 164 patients randomized to symptom-triggered therapy compared to 6 out of 164 randomized to fixed dose therapy (odds ratio, 0.64 [95% CI, 0.17-2.47]). Three studies reported duration of therapy, which was 60.4h less with symptom-triggered therapy (95% CI, 39.7-81.1h; p < 0.001). Six studies reported total benzodiazepine dosage, which was 10.5mg in lorazepam-equivalent dosing less with symptom-triggered therapy (95% CI, 7.1-13.9mg; p = 0.011). Moderate strength evidence suggests that symptom-triggered therapy improved duration of therapy and total benzodiazepine dose in specialized detoxification settings of low-risk patients but the applicability of this evidence in general hospital settings is low. There was insufficient evidence for any conclusions about symptom-triggered therapy for the major outcomes of mortality, seizure, and delirium in any setting. CRD42017073426.

Deprescribing in the Pharmacologic Management of Delirium: A Randomized Trial in the Intensive Care Unit.

Benzodiazepines and anticholinergics are risk factors for delirium in the intensive care unit (ICU). We tested the impact of a deprescribing intervention on short-term delirium outcomes. Multisite randomized clinical trial. ICUs of three large hospitals. Two hundred adults aged 18 years or older and admitted to an ICU with delirium, according to the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the ICU (CAM-ICU). Participants had a contraindication to haloperidol (seizure disorder or prolonged QT interval) or preference against haloperidol as a treatment for delirium, and were excluded for serious mental illness, stroke, pregnancy, or alcohol withdrawal. Participants were randomized to a deprescribing intervention or usual care. The intervention included electronic alerts combined with pharmacist support to deprescribe anticholinergics and benzodiazepines. Primary outcomes were delirium duration measured by the CAM-ICU and severity measured by the Delirium Rating Scale Revised-98 (DRS-R-98) and the CAM-ICU-7; secondary outcomes included adverse events and mortality. Participants had a mean age of 61.8 (SD = 14.3) years, 59% were female, and 52% were African American, with no significant differences in baseline characteristics between groups. No differences between groups were identified in the number exposed to anticholinergics (P = .219) or benzodiazepines (P = .566), the median total anticholinergic score (P = .282), or the median total benzodiazepine dose in lorazepam equivalents (P = .501). Neither median delirium/coma-free days (P = .361) nor median change in delirium severity scores (P = .582 for DRS-R-98; P = .333 for CAM-ICU-7) were different between groups. No differences in adverse events or mortality were identified. When added to state-of-the-art clinical services, this deprescribing intervention had no impact on medication use in ICU participants. Given the age of the population, results of clinical outcomes may not be easily extrapolated to older adults. Nonetheless, improved approaches for deprescribing or preventing anticholinergics and benzodiazepines should be developed to determine the impact on delirium outcomes. J Am Geriatr Soc 67:695-702, 2019.

Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2x2 factorial trial.

Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial no blinded studies have been performed. The objective of this study is to establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus. Secondary objectives: to determine whether the addition of intrathecal tetanus antitoxin reduces autonomic nervous system dysfunction and length of hospital/ intensive care unit stay; whether the addition of intrathecal tetanus antitoxin in the treatment of tetanus is safe and cost-effective; to provide data to inform recommendation of human rather than equine antitoxin. This study will enroll adult patients (≥16 years old) with tetanus admitted to the Hospital for Tropical Diseases, Ho Chi Minh City. The study is a 2x2 factorial blinded randomized controlled trial. Eligible patients will be randomized in a 1:1:1:1 manner to the four treatment arms (intrathecal treatment and human intramuscular treatment, intrathecal treatment and equine intramuscular treatment, sham procedure and human intramuscular treatment, sham procedure and equine intramuscular treatment). Primary outcome measure will be requirement for mechanical ventilation. Secondary outcome measures: duration of hospital/ intensive care unit stay, duration of mechanical ventilation, in-hospital and 240-day mortality and disability, new antibiotic prescription, incidence of ventilator associated pneumonia and autonomic nervous system dysfunction, total dose of benzodiazepines and pipecuronium, and incidence of adverse events. Trial registration: ClinicalTrials.gov NCT02999815 Registration date: 21 December 2016.

Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2x2 factorial trial

Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial no blinded studies have been performed. The objective of this study is to establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus. Secondary objectives: to determine whether the addition of intrathecal tetanus antitoxin reduces autonomic nervous system dysfunction and length of hospital/ intensive care unit stay; whether the addition of intrathecal tetanus antitoxin in the treatment of tetanus is safe and cost-effective; to provide data to inform recommendation of human rather than equine antitoxin. This study will enroll adult patients (≥16 years old) with tetanus admitted to the Hospital for Tropical Diseases, Ho Chi Minh City. The study is a 2x2 factorial blinded randomized controlled trial. Eligible patients will be randomized in a 1:1:1:1 manner to the four treatment arms (intrathecal treatment and human intramuscular treatment, intrathecal treatment and equine intramuscular treatment, sham procedure and human intramuscular treatment, sham procedure and equine intramuscular treatment). Primary outcome measure will be requirement for mechanical ventilation. Secondary outcome measures: duration of hospital/ intensive care unit stay, duration of mechanical ventilation, in-hospital and 240-day mortality and disability, new antibiotic prescription, incidence of ventilator associated pneumonia and autonomic nervous system dysfunction, total dose of benzodiazepines and pipecuronium, and incidence of adverse events. Trial registration: ClinicalTrials.gov NCT02999815 Registration date: 21 December 2016

Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2x2 factorial trial

Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial no blinded studies have been performed. The objective of this study is to establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus. Secondary objectives: to determine whether the addition of intrathecal tetanus antitoxin reduces autonomic nervous system dysfunction and length of hospital/ intensive care unit stay; whether the addition of intrathecal tetanus antitoxin in the treatment of tetanus is safe and cost-effective; to provide data to inform recommendation of human rather than equine antitoxin. This study will enroll adult patients (≥16 years old) with tetanus admitted to the Hospital for Tropical Diseases, Ho Chi Minh City. The study is a 2x2 factorial blinded randomized controlled trial. Eligible patients will be randomized in a 1:1:1:1 manner to the four treatment arms (intrathecal treatment and human intramuscular treatment, intrathecal treatment and equine intramuscular treatment, sham procedure and human intramuscular treatment, sham procedure and equine intramuscular treatment). Primary outcome measure will be requirement for mechanical ventilation. Secondary outcome measures: duration of hospital/ intensive care unit stay, duration of mechanical ventilation, in-hospital and 240-day mortality and disability, new antibiotic prescription, incidence of ventilator associated pneumonia and autonomic nervous system dysfunction, total dose of benzodiazepines and pipecuronium, and incidence of adverse events. Trial registration: ClinicalTrials.gov NCT02999815 Registration date: 21 December 2016

MP43: Evaluation of an innovative web-based educational program to teach the management of alcohol withdrawal

Introduction: Ideal management of alcohol withdrawal syndrome (AWS) incorporates a symptom driven approach, whereby patients are regularly assessed using a standardized scoring system (Clinical Institute Withdrawal Assessment for Alcohol-Revised; CIWA-Ar) and treated according to severity. Accurate administration of the CIWA-Ar requires experience, yet there is no training program to teach this competency. The objective of this study was to develop and evaluate a web-based curriculum to teach clinicians how to accurately assess and treat AWS. Methods: This was a three-phase educational program consisting of a series of 3 e-learning modules of core competency material, in-person seminar to orient learners to high fidelity simulation, and summative evaluation in an OSCE setting using a standardized patient. To determine the ED impact of the AWS curriculum, we recorded how often the CIWA-Ar was appropriately applied in the ED pre and post training. ED length of stay, total dose of benzodiazepines administered in the ED, and number of prescriptions and unit benzodiazepine doses given upon discharge were also recorded. Results: 74 nurses from an academic ED completed the AWS curriculum. There were 130 and 126 patients in the pre and post AWS training periods, respectively. Management of AWS was not compliant with CIWA-Ar protocol in 78 (60.0%) and 46 (36.5%) patients pre and post AWS training, respectively ( 23.5%; 95% CI: 11.3%, 34.7%), resulting in administration of benzodiazepine when it was not required, or not giving benzodiazepines with a CIWA-Ar score of 10. There was an average of 4 CIWA-Ar scores per patient in both the pre and post implementation periods. Prior to AWS training, 144/560 (25.5%) CIWA-Ar scores resulted in a breach of protocol, compared to 64/547 (11.7%) following AWS training ( 13.8%; 95% CI: 9.3%, 18.3%). Median total dose of benzodiazepines administered in the ED was lower after the implementation of the AWS curriculum (40mg vs 30mg; 10 mg; 95% CI: 0mg, 20mg). ED length of stay and the amount of benzodiazepines given to patients at discharge were similar between groups. Conclusion: This AWS curriculum appears to be an effective way to train ED clinicians on the proper administration of the CIWA-Ar protocol, and results in improved patient care.

Use of antipsychotics and benzodiazepines in connection to minimising coercion and mechanical restraint in a general psychiatric ward.

Decrease in coercive measures can lead to increased exposure to antipsychotics and benzodiazepines. This is not desirable as these drugs are associated with harmful side effects and reduced life expectancy. To quantify and compare the use of antipsychotic and anxiolytic medications in connection with the implementation of a programme to reduce coercion and restraint. Observational study in a general psychiatric ward comparing psychopharmacological treatment after implementation of non-pharmacological interventions to reduce coercion and mechanical restraint with a historical reference cohort from the same ward. Data from 101 admissions after implementation of interventions were compared with data from 85 admissions in a historical reference cohort. Mean defined daily doses of antipsychotics, benzodiazepines or the total amount of both showed no difference before and after implementation of the programme. Standardised regression coefficients (β) from a mixed effects linear regression model, adjusted for age, gender, length of admission, involuntary admission and history of substance abuse showed that neither total dose of antipsychotics (adjusted β: .05, 95% confidence interval (CI): -0.20 to 0.31), total dose of benzodiazepines (adjusted β: -.13, 95%CI: -.42 to 0.16) nor total amount of both drugs (adjusted β: .00, 95%CI: -.26 to 0.21) increased after implementation. Decrease in coercive measures from 2013 to 2016 has not lead to significant increases in the use of antipsychotic medication or benzodiazepines. The interventions are useful in establishing restraint-free wards, and careful monitoring of the psychopharmacological treatment is important for patient safety.