Administration Of Benzodiazepines Research Articles

Characterization of post-ictal clinical signs in dogs with idiopathic epilepsy: A questionnaire-based study.

Post-ictal (PI) clinical signs are a key defining stage of seizure manifestation in dogs. However, this phase remains poorly understood. To further characterize PI signs and their relation to other parts of a seizure, and understand the owner's perception of how PI signs affect the quality of life (QOL) of the dog. Eight-seven dogs with a diagnosis of idiopathic epilepsy from a single institution. The prospective questionnaire-based study surveying owners of dogs previously and newly diagnosed with idiopathic epilepsy. Post-ictal signs were identified in 79/87 dogs, 5/5 of dogs with focal seizures and 74/82 of dogs with generalized seizures. Median duration of PI signs was 30 minutes (range, 5-4320 minutes). The most common PI signs reported were disorientation (50/79) and wobbliness or clumsiness (49/79). Within a year, a change in PI signs was seen in 18/79 dogs. The administration of benzodiazepines was significantly associated with an increase in duration of PI signs (P = .04). Post-ictal signs had more impact on dogs' quality of life compared with ictal signs (P < .01). Groupings of co-existing PI signs identified included disorientation, blindness and deafness. Post-ictal signs are a commonly reported aspect of seizures in dogs with idiopathic epilepsy, both in focal as well as generalized seizures. Co-existence of signs could provide some valuable insight into the relevance of this particular phase of a seizure. Owner-reported signs and documentation emphasize the need for a better understanding of PI signs in dogs with idiopathic epilepsy.

Prevalence and Incidence of Oral Benzodiazepine Use in Hospitalized Surgical Patients: A Retrospective Cohort Study.

To determine the prevalence of intrahospital oral benzodiazepine use in the surgical population of a tertiary care centre. Oral benzodiazepines used for treating sleep disturbances and anxiety are widely used in the general population. Information regarding benzodiazepine use during hospitalization is scarce. A retrospective cohort study was conducted using routinely collected healthcare data in a university hospital in Rotterdam, the Netherlands. 10,896 patients representing 14,928 admissions were included in this cohort, corresponding to all adult surgical patients admitted between September 2018 and September 2022. Median age was 62 (50-72) and 8,761 out of 14928 (58.9%) were male. Main outcome measures were prevalence and incidence of oral benzodiazepines usage during hospitalization. Prevalence of benzodiazepine administrations in the surgical department was 21.6% out of 14,928 admissions. Median number of tablets given during hospital stay was 3 (1-7). Temazepam (33%), oxazepam (24%) and zopiclone (19%) were prescribed most. Female patients were more likely to have been administered a benzodiazepine, with an adjusted odds ratio of 1.09 (95% confidence interval 1.002 to 1.19). Benzodiazepine administration during admission was positively associated with higher 30-day surgical readmission, with an adjusted odds ratio of 1.37 (1.22 to 1.54). In this study, one fifth of patients admitted to surgical departments were administered oral benzodiazepines for sleep disturbances and anxiety. Future research and policies should focus on finding and implementing effective non-pharmacological methods for perioperative sleep disturbances and anxiety.

Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium

Delirium is common after cardiac surgery and associated with adverse outcomes. Intraoperative benzodiazepines may increase postoperative delirium but restricting intraoperative benzodiazepines has not yet been evaluated in a randomized trial. To determine whether an institutional policy of restricted intraoperative benzodiazepine administration reduced the incidence of postoperative delirium. This pragmatic, multiperiod, patient- and assessor-blinded, cluster randomized crossover trial took place at 20 North American cardiac surgical centers. All adults undergoing open cardiac surgery at participating centers during the trial period were included through a waiver of individual patient consent between November 2019 and December 2022. Institutional policies of restrictive vs liberal intraoperative benzodiazepine administration were compared. Hospitals (clusters) were randomized to cross between the restricted and liberal benzodiazepine policies 12 to 18 times over 4-week periods. The primary outcome was the incidence of delirium within 72 hours of surgery as detected in routine clinical care, using either the Confusion Assessment Method-Intensive Care Unit or the Intensive Care Delirium Screening Checklist. Intraoperative awareness by patient report was assessed as an adverse event. During the trial, 19 768 patients (mean [SD] age, 65 [12] years; 14 528 [73.5%] male) underwent cardiac surgery, 9827 during restricted benzodiazepine periods and 9941 during liberal benzodiazepine periods. During restricted periods, clinicians adhered to assigned policy in 8928 patients (90.9%), compared to 9268 patients (93.2%) during liberal periods. Delirium occurred in 1373 patients (14.0%) during restricted periods and 1485 (14.9%) during liberal periods (adjusted odds ratio [aOR], 0.92; 95% CI, 0.84-1.01; P = .07). No patient spontaneously reported intraoperative awareness. In intention-to-treat analyses, restricting benzodiazepines during cardiac surgery did not reduce delirium incidence but was also not associated with an increase in the incidence of patient-reported intraoperative awareness. Given that smaller effect sizes cannot be ruled out, restriction of benzodiazepines during cardiac surgery may be considered. Research is required to determine whether restricting intraoperative benzodiazepines at the patient level can reduce the incidence of postoperative delirium. ClinicalTrials.gov Identifier: NCT03928236.

The impact of remimazolam compared to propofol on postoperative delirium: a systematic review and meta-analysis.

The administration of benzodiazepines has been linked to the occurrence of postoperative delirium (POD) among patients undergoing surgery. In this review, we aim to appraise the current controversy regarding the role of remimazolam in POD. A systematic review and meta-analysis of randomized controlled trials was conducted to examine the effects of remimazolam administration on postoperative delirium compared to propofol from inception to April 2024. We conducted a comprehensive search of PubMed, EMBASE, Cochrane Library, Web of Science, Wanfang, and ZhiWang Chinese databases. In the fixed-effects and random-effects statistical models, pooled risk ratios (RRs) or mean differences, 95% CIs, and P values were estimated for endpoints. The trial sequential analysis was used for sensitivity analysis. Among the 479 records screened, 11 randomized controlled trials with 1682 patients were eligible for inclusion. POD did not differ between groups (RR,0.82; 95% CI 0.53-1.26; P=0.36; df=10; I2=42%). There were no statistically significant differences between groups in the incidence of nausea and vomiting, hypoxemia, and length of stay. However, remimazolam had a lower incidence of hypotension and bradycardia than propofol. Analyses of subgroups did not reveal a difference in delirium based on the type of surgery, assessment timing, or definition of cognitive impairment. This result has been supported by the trial sequential analysis. Based on the available evidence, perioperative remimazolam administration is not associated with a significant rise in the incidence of POD.

Nurses' attitudes, beliefs and knowledge of sleep health in residential aged care: An integrative literature review.

To identify, synthesize and evaluate primary research on registered nurses' (RN) knowledge, attitudes and beliefs about sleep health and sleep health management of older adults living in residential aged care. Integrative review. Medline, Embase and CINAHL databases from inception to September 2023. Databases were searched using a combination of key words, subject heading terms. All abstracts and full-text articles were screened by two researchers. Qualitative synthesis of the included articles was conducted. Inductive content analysis was used to identify themes and analyse data. A total of 923 abstracts were screened resulting in a final yield of 13 articles. Three themes were identified: (i) RN experience with sleep-disturbed residents, (ii) the emotional burden of sleep disturbances on RN and, (iii) organizational barriers to promoting resident's healthy sleep. Inappropriate administration of benzodiazepines and psychotropic drugs to manage residents' sleep disturbances was a major issue and lack of resources in residential aged care to facilitate sleep. There were concerns on nursing activity that disturbed residents' sleep and striking a balance between facilitating sleep and meeting managerial expectations was challenging. This review identified that nurses' decision-making has an integral role in the management of sleep health in residents in aged care. Whilst evidence-based guidelines for managing sleep in residential aged care are available, there is a lack of translation to practice. Understanding RN perspectives is critical to improving sleep health models of care in residential aged care. This review found that RN are attuned to the implications of sleep disturbance in residential aged care but are constrained by current sleep health models of care. Not applicable.

Delirium Management Quality Improvement Project to Improve Awareness and Screening in a Medical ICU.

Background/Objectives: Although delirium is common during critical illness, standard-of-care detection and prevention practices in real-world intensive care unit (ICU) settings remain inconsistent, often due to a lack of provider education. Despite availability for over 20 years of validated delirium screening tools such as the Confusion Assessment Method in the ICU (CAM-ICU), feasible and rigorous educational efforts continue to be needed to address persistent delirium standard-of-care practice gaps. Methods: Spanning an 8-month quality improvement project period, our single-ICU interdisciplinary effort involved delivery of CAM-ICU pocket cards to bedside nurses, and lectures by experienced champions that included a live delirium detection demonstration using the CAM-ICU, and a comprehensive discussion of evidence-based delirium prevention strategies (e.g., benzodiazepine avoidance). Subsequent engagement by health system leadership motivated the development of an electronic health record dataset to evaluate unit-level outcomes, including CAM-ICU documentation and benzodiazepine administration. Results: Using a dataset that spanned 9 pre- and 37 post-project months and included 3612 patients, 4470 admissions, and 33,913 patient days, we observed that delirium education was followed by a dramatic rise in CAM-ICU documentation, from <1% for daytime and nighttime shifts to peaks of 73% and 71%, respectively (p < 0.0001 for trend), and a fall in the proportion of mechanically ventilated patients ever receiving benzodiazepine infusions (69% to 41%; p < 0.0001). Conclusions: An interdisciplinary delirium project comprising rigorous lectures on standard-of-care practices can yield significant improvements in documentation and sedative administration. This approach can help ICUs jumpstart efforts to build awareness and address longstanding gaps in standard-of-care delirium practices.

Leading symptom: motor manifestations with impaired consciousnes : Management of epileptic seizures and status epilepticus

Epileptic seizures, which are often accompanied by areduction in vigilance, are acommon emergency. Every first-time epileptic seizure should be investigated further. Particular attention should be paid to whether it is an acute symptomatic seizure, which is an acute event characterized by ametabolic disorder or acute cerebral damage within acertain period of time, or possibly epilepsy. In terms of differential diagnosis, psychogenic nonepileptic seizures also pose achallenge, as they are often not easy to distinguish from epileptic seizures, but require adifferent therapeutic approach. Persistent epileptic seizures in the sense of status epilepticus (duration: > 5 min) are also common in the (pre)clinical emergency situation and require immediate initiation of adequate therapy, which consists of rapid and sufficient administration of benzodiazepines. Nasal administration is aquick and simple option here, particularly in the prehospital setting. Furthermore, persistent reductions in vigilance are anot infrequently occurring phenomenon in the (pre)clinical setting, which is, however, based on numerous differential diagnoses. Here, nonconvulsive status epilepticus should be considered as apossible cause and rapid diagnosis using EEG should be sought in order to begin early treatment, which improves patient outcomes.

Intranasal midazolam as an alternative to rectal diazepam for management of canine status epilepticus

Question In canine patients in status epilepticus, is intranasal midazolam as effective as rectal diazepam for controlling seizures? Clinical bottom line The category of research question was: Treatment. The number and type of study designs that were critically appraised were: One study was found—a multicentre randomised open-label clinical trial comparing intranasal midazolam and rectal diazepam in canine patients. Critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero/weak/moderate/strong evidence in terms of their experimental design and implementation: Weak. The outcomes reported are summarised as follows… The study critically appraised in this summary indicated that intranasal midazolam is effective in achieving seizure control in canine patients, with tolerable safety margins. Mild adverse effects associated with benzodiazepine administration such as sedation and drowsiness were noted, but there were no reports of serious adverse events related to the use of intranasal midazolam. In view of the strength of evidence and the outcomes from the studies the following conclusion is made… Intranasal midazolam appears to be safe and effective for achieving seizure control in canine patients, both in terms of efficacy and speed of onset, and is a suitable first-line treatment option for status epilepticus, especially when intravenous access is not rapidly available. Patients should be monitored after drug administration for development of adverse effects, including sedation, sneezing, and nasal irritation. A nasal mucosal atomisation device may be used to enhance bioavailability of the drug, improving efficacy.

Strategies to Limit Benzodiazepine Use in Anesthesia for Older Adults

Despite guidelines recommending avoidance of benzodiazepine administration to older patients, many of them now receive benzodiazepines as a part of anesthesia care. The effectiveness of clinician- and patient-facing interventions to discourage such use remains insufficiently characterized. To evaluate the effect of clinician peer comparison, patient informational mail, or a combination of these interventions compared with usual care on the rate of perioperative benzodiazepine administration to older patients. This 2 × 2 factorial, stepped-wedge, cluster randomized clinical trial of a corporate quality improvement initiative was conducted between August 8, 2022, and May 28, 2023, across 415 hospitals, surgery centers, and physician offices in 8 US states served by anesthesia clinicians from a national anesthesia practice. Participants were adults aged 65 years or older who underwent an elective surgical or endoscopic procedure with general anesthesia. Data analyses followed the intention-to-treat principle. Patients were randomly assigned to 1 of 4 groups-clinician peer comparison (wherein clinicians received feedback regarding their performance compared with other clinicians in the practice), patient informational mail (wherein patients received an informational letter encouraging them to have a discussion regarding medication selection with their clinician on the day of surgery), both interventions, or usual care (no intervention). Rate of benzodiazepine administration during anesthesia care and patient satisfaction with anesthesia care (measured by the Anesthesia Patient Satisfaction Questionnaire, version 2). Among the 509 269 enrolled participants (255 871 females [50.2%]; mean [SD] age, 74 [7] years), 81 363 (16.0%) were assigned to clinician peer comparison, 98 520 (19.3%) to patient informational mail, 169 712 (33.3%) to both interventions, and 159 674 (31.4%) to usual care. Among patients who received benzodiazepine during anesthesia care, 24.5% were in the usual care group compared with 19.7% in the clinician peer comparison group, 20.0% in the patient informational mail group, and 19.7% in the combination group. After adjustment for time, none of the study interventions were associated with lower odds of benzodiazepine administration compared with usual care (odds ratio [OR], 1.02 [95% CI, 0.98-1.07]; P = .35 for clinician peer comparison; OR, 1.01 [95% CI, 0.96-1.05]; P = .81 for patient informational mail; and OR, 1.11 [95% CI, 1.05-1.16]; P < .001 for combined interventions). Satisfaction scores were high in all groups and did not vary by treatment assignment. This randomized clinical trial found that clinician peer comparison, patient informational mail, or a combination of both interventions did not reduce benzodiazepine administration to older patients compared with usual care; patient satisfaction remained high throughout the study. Overall, the findings suggest a need to explore other patient-targeted interventions to improve anesthesia care. Clinicaltrials.gov Identifier: NCT05436392.

Effects of lorazepam on saccadic eye movements – evidence from prosaccade and free viewing tasks

RationalePeak velocities of saccadic eye movements are reduced after benzodiazepine administration. Even though this is an established effect, past research has only examined it in horizontal prosaccade tasks.ObjectivesThe spectrum of saccadic eye movements, however, is much larger. Therefore, we aimed to make a first attempt at filling this research gap by testing benzodiazepine effects on saccades under different experimental task conditions.Methods1 mg lorazepam or placebo was administered (within-subjects, double-blind, in randomised order) to n = 30 healthy adults. Participants performed an extended version of the prosaccade task, including vertical saccade directions and different stimulus eccentricities, as well as a free viewing task.ResultsResults from the prosaccade task confirmed established effects of benzodiazepines as well as saccade direction on saccadic parameters but additionally showed that the drug effect on peak velocity was independent of saccade direction. Remarkably, in the free viewing task peak velocities as well as other saccade parameters were unaffected by lorazepam. Furthermore, exploration patterns during free viewing did not change under lorazepam.ConclusionsOverall, our findings further consolidate the peak velocity of prosaccades as a biomarker of sedation. Additionally, we suggest that sedative effects of low doses of benzodiazepines may be compensated in tasks that more closely resemble natural eye movement behaviour, possibly due to the lack of time constraints or via neurophysiological processes related to volition.

Patient, Practice, and Organizational Factors Associated With Early Mobility Performance in Critically Ill Adults.

Adoption of early mobility interventions into intensive care unit (ICU) practice has been slow and varied. To examine factors associated with early mobility performance in critically ill adults and evaluate factors' effects on predicting next-day early mobility performance. A secondary analysis of 66 ICUs' data from patients admitted for at least 24 hours. Mixed-effects logistic regression modeling was done, with area under the receiver operating characteristic curve (AUC) calculated. In 12 489 patients, factors independently associated with higher odds of next-day mobility included significant pain (adjusted odds ratio [AOR], 1.16; 95% CI, 1.09-1.23), documented sedation target (AOR, 1.09; 95% CI, 1.01-1.18), performance of spontaneous awakening trials (AOR, 1.77; 95% CI, 1.59-1.96), spontaneous breathing trials (AOR, 2.35; 95% CI, 2.14-2.58), mobility safety screening (AOR, 2.26; 95% CI, 2.04-2.49), and prior-day physical/occupational therapy (AOR, 1.44; 95% CI, 1.30-1.59). Factors independently associated with lower odds of next-day mobility included deep sedation (AOR, 0.44; 95% CI, 0.39-0.49), delirium (AOR, 0.63; 95% CI, 0.59-0.69), benzodiazepine administration (AOR, 0.85; 95% CI, 0.79-0.92), physical restraints (AOR, 0.74; 95% CI, 0.68-0.80), and mechanical ventilation (AOR, 0.73; 95% CI, 0.68-0.78). Black and Hispanic patients had lower odds of next-day mobility than other patients. Models incorporating patient, practice, and between-unit variations displayed high discriminant accuracy (AUC, 0.853) in predicting next-day early mobility performance. Collectively, several modifiable and nonmodifiable factors provide excellent prediction of next-day early mobility performance.

Efficiency and safety of high-dose undiluted intravenous push levetiracetam loading doses compared to intravenous infusion in seizing patients: A retrospective cohort study.

Intravenous (IV) push (IVP) is an alternative administration method for levetiracetam, but evidence evaluating it compared to IV piggyback (IVPB) for loading doses in acutely seizing patients is limited, particularly in patients with status epilepticus (SE). This study aimed to compare the efficiency and safety of IVP versus IVPB levetiracetam loading doses. This was a single-center sequential retrospective study conducted in adult (≥18 years) patients who received an IV levetiracetam loading dose (>2000 mg or ≥20 mg/kg) for acute or suspected seizure. The primary outcome was time to administration, compared between doses given as IVP versus IVPB. Secondary outcomes included rates of adverse events (AEs), rescue benzodiazepine or antiseizure medication administration, intubation, and intensive care unit (ICU) admission between groups. A total of 246 patients were included; 116 received IVP and 130 received IVPB loading doses. Median age was 56 years; most patients were male (62%) and White (60%) and had witnessed seizures (67%). Doses were administered for SE in 32 (27.5%) and 46 (35.4%) patients in the IVP and IVPB arms, respectively. Median time to administration was shorter in the IVP group (12 vs. 38 min, p < .001). Bradycardia (1.7% vs. 2.3%, p = .99), hypotension (7.8% vs. 12%, p = .30), sedation (6% vs. 12.3%, p = .09), intubation (10% vs. 8%, p = .37), ICU admission (32% vs. 39%, p = .31), and rescue medication administration (8.6% vs. 14.6% p = .10) were similar between groups. In SE patients, IVP was associated with shorter time to administration (12 vs. 44 min, p = .003) and lower odds of ICU admission after adjustment for age, dose, Status Epilepticus Severity Score, and seizure history (adjusted odds ratio = .23, 95% confidence interval = .06-.81). IVP reduced time to levetiracetam administration versus IVPB and was not associated with more AEs. Rescue agent use, intubation, and ICU admission were similar between arms, but IVP may reduce ICU admissions in SE patients. Prospective studies should assess the effectiveness of IVP versus IVPB.

Challenges of status epilepticus management in a resource-limited setting: A review

Status epilepticus (SE) is a life-threatening neurological condition with significant mortality. Rapid management is essential to minimize the mortality and disability of SE. Two recent trials provided evidence to guide SE management in early and established stages. The Rapid Anticonvulsant Medication Prior To Arrival Trial (RAMPART, 2011) showed that intramuscular midazolam is a better alternative for early convulsive SE in prehospital settings. The Established Status Epilepticus Treatment Trial (ESETT, 2020) supported the use of sodium valproate and levetiracetam as second-line treatment for its efficacy and shorter administration time. However, there are challenges to revising the status epilepticus management in resource-limited settings, in pre-hospital, first- and second-line treatment, as well as management of refractory and super-refractory SE. These challenges included restrictions or lack of training in the administration of benzodiazepine in the prehospital setting, limited availability and accessibility of newer antiseizure medications (ASMs) in emergency departments and smaller hospitals, and low clinicians’ awareness of the latest evidence. A collaborative effort to educate, improve awareness, and make certain ASMs more readily available is recommended to achieve a better clinical outcome in SE.

Status epilepticus management in patients with brain tumors. A cohort study

PurposeStatus epilepticus (SE) represents a neurological emergency with significant morbidity and mortality. SE in patients with primary brain tumors received only limited attention to date; detailed analysis of treatment flow is lacking, especially as compared to other SE causes. This study aims to describe the frequency and treatment flow of tumor-related SE and compare it to other SE etiologies. MethodsRetrospective cohort study based on an institutional SE registry (SERCH) comprising adult SE (excluding post-anoxic causes), treated between January 2013 and December 2022, comparing SE management, frequency of refractory SE, and clinical outcome, among four patients’ groups stratified by SE etiology: Non-neoplastic, Gliomas, Brain metastases, Other brain tumors. ResultsWe analyzed 961 episodes in 831 patients (Non-neoplastic: 649, Gliomas: 85, Metastases: 77, Other brain tumors: 20). Although tumor-patients presented more often with focal episodes and less consciousness impairment than non-neoplastic patients, administration of benzodiazepines as first-line treatment (>75% across all groups), and utilization of second-line ASM were similar across groups. Treatment adequacy was marginally higher in glioma patients compared to the non-neoplastic population (p: 0.049), while refractory SE was comparable in all groups (p: 0.269). No significant differences in clinical outcomes were observed (mortality: non-neoplastic (89/649, 13.7%), glioma (8/85, 9.4%), metastases (14/77, 18.2%), other tumors (5/20, 25.0%), p: 0.198; non-neoplastic vs. glioma, p: 0.271) ConclusionTumor-associated SE represents 1/5 of all SE episodes, and is managed similarly to other SE causes. Treatment responsiveness and short-term clinical outcomes also exhibit comparable results.

Respiratory Effects of Benzodiazepine in Patients with Advanced-Stage Cancer Receiving Opioid Analgesics: A Prospective Observational Study.

Despite the risk of respiratory depression, benzodiazepines are often prescribed to patients receiving palliative care owing to their efficacy in symptom control. Opioids, which also cause respiratory depression, are often administered to patients with advanced-stage cancer. However, the additive effect of the two drugs has not been systematically analyzed. This prospective observational study aimed to determine the respiratory effects of coadministration of benzodiazepines and opioids in terminally ill patients with cancer. The respiratory variables (primary endpoint) and activity index (ACI) (secondary endpoint) of 24 patients were assessed using a continuous noncontact, nonrestraining vital sign monitor placed under the legs of the bed. The respiratory rate (RR) changed from 12.0 ± 3.9/min to 10.3 ± 3.3/min (n = 24, p = 0.0005) following administration of the first dose of benzodiazepine in addition to regular opioid treatment, indicating no difference (p > 0.83) from the decrease in the RR observed on the previous day at the same time (12.1 ± 3.3/min to 10.3 ± 3.4/min). No increase in apnea-hypopnea frequency and respiratory irregularity or no decrease in respiratory size was observed. The ACI showed a significant decrease following the administration of benzodiazepine, suggesting remission of the symptoms. The effect of five repeated doses of benzodiazepines in nine patients showed no significant change in the respiratory variables compared with the first dose. Addition of single or consecutive benzodiazepine-type drugs at clinically useful dose in patients receiving palliative care for cancer with opioid analgesics, readily exposed to respiratory depression, was observed with a decreased RR similar to the decrease observed during sleep with opioid alone.

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 < .001), decreased use of concomitant benzodiazepine/phenobarbital (4.3% vs 28.9%; P < .001), and decreased total benzodiazepine dose (7.8 vs 15.5 mg; P < .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.

Management of alcohol withdrawal syndrome in patients with alcohol-associated liver disease.

Alcohol-associated liver disease is a common and severe sequela of excessive alcohol use; effective treatment requires attention to both liver disease and underlying alcohol use disorder (AUD). Alcohol withdrawal syndrome (AWS) can be dangerous, is a common barrier to AUD recovery, and may complicate inpatient admissions for liver-related complications. Hepatologists can address these comorbid conditions by learning to accurately stage alcohol-associated liver disease, identify AUD using standardized screening tools (eg, Alcohol Use Disorder Identification Test), and assess risk for and symptoms of AWS. Depending on the severity, alcohol withdrawal often merits admission to a monitored setting, where symptom-triggered administration of benzodiazepines based on standardized scoring protocols is often the most effective approach to management. For patients with severe liver disease, selection of benzodiazepines with less dependence on hepatic metabolism (eg, lorazepam) is advisable. Severe alcohol withdrawal often requires a "front-loaded" approach with higher dosing, as well as intensive monitoring. Distinguishing between alcohol withdrawal delirium and HE is important, though it can be difficult, and can be guided by differentiating clinical characteristics, including time to onset and activity level. There is little data on the use of adjuvant medications, including anticonvulsants, dexmedetomidine, or propofol, in this patient population. Beyond the treatment of AWS, inpatient admission and outpatient hepatology visits offer opportunities to engage in planning for ongoing management of AUD, including initiation of medications for AUD and referral to additional recovery supports. Hepatologists trained to identify AUD, alcohol-associated liver disease, and risk for AWS can proactively address these issues, ensuring that patients' AWS is managed safely and effectively and supporting planning for long-term recovery.

Screening for Alcohol Use Disorder and Management of Alcohol Withdrawal Syndrome in Critical Care Patients.

Evidence-based research indicates that subjective questionnaires should be eliminated in screening for alcohol use disorder and management of alcohol withdrawal syndrome in critical care patients. However, transitioning clinicians away from these screening tools remains challenging. To improve screening for alcohol use disorder and management of alcohol withdrawal syndrome in the critical care setting by implementing an evidence-based alcohol use disorder screening tool and alcohol withdrawal syndrome protocol for critical care patients. The project site was a 17-bed adult medical intensive care unit in a large, southeastern US teaching hospital. Interventions consisted of the elimination of previously used tools such as the Clinical Institute Withdrawal Assessment for Alcohol-Revised and implementation of the Prediction of Alcohol Withdrawal Severity Scale for alcohol use disorder screening and the Richmond Agitation-Sedation Scale and symptom-triggered benzodiazepine administration for alcohol withdrawal syndrome management. Alcohol use disorder screening among the critical care patient population increased by 49% from before to after the intervention. Of the patients at risk for withdrawal, 79% had an order for monitoring with the new intensive care unit alcohol withdrawal protocol in the postintervention group, compared with 35% who had an order for monitoring with the Clinical Institute Withdrawal Assessment for Alcohol-Revised in the preintervention group. The elimination of previously used tools and the implementation of the Prediction of Alcohol Withdrawal Severity Scale and the new intensive care unit alcohol withdrawal protocol improved alcohol use disorder screening and alcohol withdrawal syndrome management among critical care patients.

Incidence of Adverse Events Using Flumazenil in Patients With Iatrogenic Benzodiazepine Delirium: A Retrospective Study.

Flumazenil is a competitive benzodiazepine (BZD) antagonist most used for treating delirium in BZD overdoses. Since its introduction, many have expressed concerns about its safety secondary to the risk of inducing BZD withdrawal and refractory seizures. What is the incidence of adverse drug events after the administration of flumazenil in patients with suspected iatrogenic BZD delirium? This is a retrospective cross-sectional study of patients from a single center from 2010 to 2013. Patients experiencing delirium after receiving BZDs in the hospital were included if they had a bedside toxicology consult and were administered flumazenil. Patients were excluded if they were given BZDs for ethanol withdrawal or if they did not have mental status documentation before and after flumazenil administration. Descriptive statistics were calculated. The primary outcome was the incidence of adverse drug events after flumazenil administration. The secondary outcome was the efficacy of flumazenil determined by the patient's mental status. A total of 501 patient records were reviewed, and 206 patients were included in the final analysis. Of those patients, 172 (83.5%) experienced an objective improvement in their mental status within 1 hour after flumazenil administration. A total of 5 patients experienced adverse events (2.4%), 95% confidence interval (0.78, 5.54). Of these, 3 patients experienced minor agitation or restlessness without pharmacologic intervention. Two patients experienced moderate agitation or restlessness that resolved with haloperidol or physostigmine administration. No patients had a reported seizure, 95% confidence interval (0.0, 1.77). Flumazenil seems to be a safe and effective intervention for the reversal of delirium secondary to iatrogenic BZD administration.

Protracted respiratory failure in a case of global spinal syringomyelia and Chiari malformation following administration of diazepam: illustrative case.

Syringomyelia is defined as dilation of the spinal cord's central canal and is often precipitated by skull base herniation disorders. Although respiratory failure (RF) can be associated with skull base abnormalities due to brainstem compression, most cases occur in pediatric patients and quickly resolve. The authors report the case of an adult patient with global spinal syringomyelia and Chiari malformation who developed refractory RF after routine administration of diazepam. A 31-year-old female presented with malnutrition, a 1-month history of right-sided weakness, and normal respiratory dynamics. After administration of diazepam prior to magnetic resonance imaging (MRI), she suddenly developed hypercapnic RF followed MRI and required intubation. MRI disclosed a Chiari malformation type I and syrinx extending from C1 to the conus medullaris. After decompressive surgery, her respiratory function progressively returned to baseline status, although 22 months after initial benzodiazepine administration, the patient continues to require nocturnal ventilation. Administration of central nervous system depressants should be closely monitored in patients with extensive syrinx formation given the potential to exacerbate diminished central respiratory drive. Early identification of syrinx in the context of Chiari malformation and hemiplegia should prompt clinical suspicion of underlying respiratory compromise and early involvement of intensive care consultants.