Long-term outcome of alcohol withdrawal seizures.

BACKGROUND AND PURPOSE: Alcohol withdrawal seizures (AWS) are a well-known complication of chronic alcohol abuse, but there is currently little knowledge of their long-term relapse rate and prognosis. The aims of this study were to identify risk factors for AWS recurrence and to study the overall outcome of patients after AWS. METHODS: In this retrospective single-center study, we included patients who were admitted to the Emergency Department after an AWS between January 1, 2013 and August 10, 2021 and for whom an electroencephalogram (EEG) was requested. AWS relapses up until April 29, 2022 were researched. We compared history, treatment with benzodiazepines or antiseizure medications (ASMs), laboratory, EEG and computed tomography findings between patients with AWS relapse (r-AWS) and patients with no AWS relapse (nr-AWS). RESULTS: A total of 199 patients were enrolled (mean age 53 ± 12 years; 78.9% men). AWS relapses occurred in 11% of patients, after a median time of 470.5 days. Brain computed tomography (n = 182) showed pathological findings in 35.7%. Risk factors for relapses were history of previous AWS (p = 0.013), skull fractures (p = 0.004) at the index AWS, and possibly epileptiform EEG abnormalities (p = 0.07). Benzodiazepines or other ASMs, taken before or after the index event, did not differ between the r-AWS and the nr-AWS group. The mortality rate was 2.9%/year of follow-up, which was 13 times higher compared to the general population. Risk factors for death were history of AWS (p < 0.001) and encephalopathic EEG (p = 0.043). CONCLUSIONS: Delayed AWS relapses occur in 11% of patients and are associated with risk factors (previous AWS >24 h apart, skull fractures, and pathological EEG findings) that also increase the epilepsy risk, that is, predisposition for seizures, if not treated. Future prospective studies are mandatory to determine appropriate long-term diagnostic and therapeutic strategies, in order to reduce the risk of relapse and mortality associated with AWS.

Phenobarbital Versus Benzodiazepines for the Treatment of Severe Alcohol Withdrawal.

BACKGROUND: Phenobarbital may offer advantages over benzodiazepines for severe alcohol withdrawal syndrome (SAWS), but its impact on clinical outcomes has not been fully elucidated. OBJECTIVE: The purpose of this study was to determine the clinical impact of phenobarbital versus benzodiazepines for SAWS. METHODS: This retrospective cohort study compared phenobarbital to benzodiazepines for the management of SAWS for patients admitted to progressive or intensive care units (ICUs) between July 2018 and July 2022. Patients included had a history of delirium tremens (DT) or seizures, Clinical Institute Withdrawal Assessment of Alcohol-Revised (CIWA-Ar) >15, or Prediction of Alcohol Withdrawal Severity Scale (PAWSS) score ≥4. The primary outcome was hospital length of stay (LOS). Secondary outcomes included progressive or ICU LOS, incidence of adjunctive pharmacotherapy, and incidence/duration of mechanical ventilation. RESULTS: The final analysis included 126 phenobarbital and 98 benzodiazepine encounters. Patients treated with phenobarbital had shorter median hospital LOS versus those treated with benzodiazepines (2.8 vs 4.7 days; P < 0.0001); a finding corroborated by multivariable analysis. The phenobarbital group also had shorter median progressive/ICU LOS (0.7 vs 1.3 days; P < 0.0001), and lower incidence of dexmedetomidine (P < 0.0001) and antipsychotic initiation (P < 0.0001). Fewer patients in the phenobarbital group compared to the benzodiazepine group received new mechanical ventilation (P = 0.045), but median duration was similar (1.2 vs 1.6 days; P = 1.00). CONCLUSION AND RELEVANCE: Scheduled phenobarbital was associated with decreased hospital LOS compared to benzodiazepines for SAWS. This was the first study to compare outcomes of fixed-dose, nonoverlapping phenobarbital to benzodiazepines in patients with clearly defined SAWS and details a readily implementable protocol.

Safety of Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal in Critically Ill Patients With Primary Neurologic Injuries.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is a complication of alcohol use disorder that manifests as a range of symptoms. Symptom-triggered benzodiazepines (BZDs) are often used as first-line treatment of AWS. However, recent literature suggests phenobarbital (PHB) may be safer and more efficacious, but studies are limited by exclusion of patients with neurological injuries. OBJECTIVE: We aimed to evaluate the safety of PHB compared to BZDs for the management of AWS among patients with primary neurologic injuries. METHODS: Retrospective cohort study of patients with primary neurologic injuries admitted to an ICU who received PHB or symptom-triggered BZD for AWS between December 2013 and February 2020. The primary outcome was incidence of oversedation, defined as Richmond Agitation Sedation Scale (RASS) scores from -5 to -3 within 24 hours of initial PHB or BZD dose. Secondary outcomes included largest decrease in RASS, need for mechanical ventilation, and additional sedative use within 24 hours of initial PHB or BZD dose. A multivariable analysis was performed to evaluate the association of PHB administration with the primary outcome. RESULTS: Among 600 patients treated for AWS, 84 patients were included in our analysis (PHB, n = 56; BZD, n = 28). In the unadjusted analysis, there were no differences between the PHB and BZD groups for the primary outcome of oversedation (21.4 vs. 7.1%, P = 0.13), or secondary outcomes of decrease in RASS (P = 0.34), or new ventilator requirement (P = 0.55). Patients who received PHB had higher rates of additional sedative use (P < 0.01). Multivariable regression revealed an increase in oversedation among intubated patients (P = 0.014), while PHB administration was not independently associated with oversedation (P = 0.516). CONCLUSION AND RELEVANCE: Phenobarbital did not independently increase the risk of oversedation compared to BZD for AWS in patients with primary neurologic injuries. Future studies should determine optimal dosing of PHB in this population.

Impact of a Divided Phenobarbital Load and Taper Compared With Lorazepam Symptom Triggered Therapy in Hospitalized Patients.

BACKGROUND: Benzodiazepines are the preferred treatment for alcohol withdrawal. Phenobarbital is an alternative in the setting of prescriber expertise or benzodiazepine contraindication. OBJECTIVE: To evaluate the efficacy and safety of a phenobarbital dosing strategy aimed at treating a spectrum of alcohol withdrawal symptoms across various patient populations. METHODS: Retrospective review of patients admitted with concerns of alcohol withdrawal between May 2018 and November 2022. Patients were separated into a before-after cohort of lorazepam or phenobarbital. The primary outcome was hospital length of stay (LOS). Secondary outcomes were intensive care unit (ICU) LOS, escalation of respiratory support, increased level of care (LOC), and incidence of delirium tremens and/or seizures. RESULTS: Two hundred and seventy-seven patients received lorazepam and 198 received phenobarbital. Hospital LOS was longer in the phenobarbital cohort compared with the lorazepam cohort (6.9 vs 9.3 days). There was no difference in ICU LOS. Level of care increases were fewer in the phenobarbital cohort (4 events vs 19 events). There were higher rates of non-invasive respiratory interventions in the lorazepam cohort and higher rates of mechanical ventilation in the phenobarbital cohort. Utilization of phenobarbital was attributed to a reduction in delirium tremens and seizures. CONCLUSION AND RELEVANCE: This study is novel because of the broad application of a phenobarbital order set across multiple levels of care and patient admission diagnoses. A risk targeted split load intravenous phenobarbital order set can safely be administered to patients with fewer escalations of care, seizures, delirium tremens, and respiratory care escalation.

Naturalistic comparison of clomethiazole and Diazepam treatment in alcohol withdrawal: effects on oxidative stress, inflammatory cytokines and hepatic biomarkers.

Ethanol is metabolized by alcohol dehydrogenase to acetaldehyde and induces cytochrome P450 2E1 (CYP2E1), which generates reactive oxygen species that cause inflammatory liver damage. Clomethiazole, a drug approved for alcohol withdrawal treatment (AWT) in some European countries, inhibits CYP2E1. We hypothesized that clomethiazole would lead to a faster reduction in oxidative stress, inflammatory cytokines, and liver enzymes compared to diazepam treatment. We analysed respective biomarkers in 50 patients undergoing AWT and 25 healthy individuals but found no statistical difference between the two medication groups over 3-5 days. Hence, our hypothesis was not confirmed during this observation period.

ANK3 rs10994336 and ZNF804A rs7597593 polymorphisms: genetic interaction for emotional and behavioral symptoms of alcohol withdrawal syndrome.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a complex condition associated with alcohol use disorder (AUD), characterized by significant variations in symptom severity among patients. The psychological and emotional symptoms accompanying AWS significantly contribute to withdrawal distress and relapse risk. Despite the importance of neural adaptation processes in AWS, limited genetic investigations have been conducted. This study primarily focuses on exploring the single and interaction effects of single-nucleotide polymorphisms in the ANK3 and ZNF804A genes on anxiety and aggression severity manifested in AWS. By examining genetic associations with withdrawal-related psychopathology, we ultimately aim to advance understanding the genetic underpinnings that modulate AWS severity. METHODS: The study involved 449 male patients diagnosed with alcohol use disorder. The Self-Rating Anxiety Scale (SAS) and Buss-Perry Aggression Questionnaire (BPAQ) were used to assess emotional and behavioral symptoms related to AWS. Genomic DNA was extracted from peripheral blood, and genotyping was performed using PCR. RESULTS: Single-gene analysis revealed that naturally occurring allelic variants in ANK3 rs10994336 (CC homozygous vs. T allele carriers) were associated with mood and behavioral symptoms related to AWS. Furthermore, the interaction between ANK3 and ZNF804A was significantly associated with the severity of psychiatric symptoms related to AWS, as indicated by MANOVA. Two-way ANOVA further demonstrated a significant interaction effect between ANK3 rs10994336 and ZNF804A rs7597593 on anxiety, physical aggression, verbal aggression, anger, and hostility. Hierarchical regression analyses confirmed these findings. Additionally, simple effects analysis and multiple comparisons revealed that carriers of the ANK3 rs10994336 T allele experienced more severe AWS, while the ZNF804A rs7597593 T allele appeared to provide protection against the risk associated with the ANK3 rs10994336 mutation. CONCLUSION: This study highlights the gene-gene interaction between ANK3 and ZNF804A, which plays a crucial role in modulating emotional and behavioral symptoms related to AWS. The ANK3 rs10994336 T allele is identified as a risk allele, while the ZNF804A rs7597593 T allele offers protection against the risk associated with the ANK3 rs10994336 mutation. These findings provide initial support for gene-gene interactions as an explanation for psychiatric risk, offering valuable insights into the pathophysiological mechanisms involved in AWS.

Polygenic influences on the behavioral effects of alcohol withdrawal in a mixed-ancestry population from the collaborative study on the genetics of alcoholism (COGA).

Alcohol withdrawal (AW) is a feature of alcohol use disorder that may occur in up to half of individuals with chronic, heavy alcohol consumption whenever alcohol use is abruptly stopped or significantly reduced. To date, few genes have been robustly associated with AW; this may be partly due to most studies defining AW as a binary construct despite the multiple symptoms and their range in severity from mild to severe. The current study examined the effects of genome-wide loci on a factor score for AW in high risk and community family samples in the Collaborative Study for the Genetics of Alcoholism (COGA). In addition, we tested whether differentially expressed genes associated with alcohol withdrawal in model organisms are enriched in human genome-wide association study (GWAS) effects. Analyses employed roughly equal numbers of males and females (mean age 35, standard deviation = 15; total N = 8009) and included individuals from multiple ancestral backgrounds. Genomic data were imputed to the HRC reference panel and underwent strict quality control procedures using Plink2. Analyses controlled for age, sex, and population stratification effects using ancestral principal components. We found support that AW is a polygenic disease (SNP-heritability = 0.08 [95 % CI = 0.01, 0.15; pedigree-based heritability = 0.12 [0.08,0.16]. We identified five single nucleotide variants that met genomewide significance, some of which have previously been associated with alcohol phenotypes. Gene-level analyses suggest a role for COL19A1 in AW; H-MAGMA analyses implicated 12 genes associated with AW. Cross-species enrichment analyses indicated that variation within genes identified in model organism studies explained <1 % of the phenotypic variability in human AW. Notably, the surrounding regulatory regions of model organism genes explained more variance than expected by chance, indicating that these regulatory regions and gene sets may be important for human AW. Lastly, when comparing the overlap in genes identified from the human GWAS and H-MAGMA analyses with the genes identified from the animal studies, there was modest overlap, indicating some convergence between the methods and organisms.

Alcohol withdrawal and amphetamine co-use in an animal model for attention deficit hyperactivity disorder.

Background: Non-medical use of amphetamine and other stimulants prescribed for treatment of attention deficit/hyperactivity disorder (ADHD) is of special concern when combined with alcohol consumption. In a previous study, we modeled chronic ethanol-amphetamine co-use in adolescent Long-Evans (LE) rats and provided evidence that amphetamine attenuates alcohol withdrawal symptoms.Objectives: This project modeled co-use of amphetamine with alcohol in adolescents with ADHD-like symptoms by examining ethanol-amphetamine administration in adolescent Spontaneously Hypertensive Rats (SHR), an experimental model for the study of ADHD. Withdrawal symptoms were compared among SHR and two control rat strains, LE and Wistar Kyoto (WKY).Methods: At postnatal day 32, parallel groups of 12-24 male SHR, WKY and LE rats were administered a liquid diet containing ethanol (3.6%) and/or amphetamine (20 mg/L). Following administration periods up to 26 days, rats were withdrawn from their treatment and tested for overall severity of alcohol withdrawal symptoms, general locomotor activity, and anxiety-like behavior.Results: Overall withdrawal severity was lower for SHR than for LE (p < .001) or WKY (p = .027). Co-consumption of amphetamine decreased withdrawal severity for LE (p = .033) and WKY (p = .011) but not SHR (p = .600). Only WKY showed increased anxiety-like behavior during withdrawal (p = .031), but not after amphetamine co-administration (p = .832).Conclusion: Alcohol withdrawal severity may be attenuated when co-used with amphetamine. However, as a model for ADHD, SHR adolescents appeared resistant to developing significant signs of alcohol withdrawal following alcohol consumption. Whether alcohol withdrawal symptoms are attenuated or absent, potential consequences could include a decreased awareness of an emerging problem with alcohol use.

A Retrospective Evaluation of Adjunctive Phenobarbital vs. Benzodiazepine Alone for the Treatment of Moderate Alcohol Withdrawal in the Emergency Department.

BACKGROUND: Phenobarbital has been used in the emergency department (ED) as both a primary and adjunctive medication for alcohol withdrawal, but previous studies evaluating its impact on patient outcomes are limited by heterogenous symptom severity. OBJECTIVES: We compared the clinical outcomes of ED patients with moderate alcohol withdrawal who received phenobarbital, with or without benzodiazepines, with patients who received benzodiazepine treatment alone. METHODS: This is a retrospective cohort study conducted at a single academic medical center utilizing chart review of ED patients with moderate alcohol withdrawal between 2015 and 2020. Patient encounters were classified into two treatment categories based on medication treatment: phenobarbital alone or in combination with benzodiazepines vs. benzodiazepines alone. Chi-square test or Fisher's exact was used to analyze categorical variables and the Student's t-test for continuous data. RESULTS: Among the 287 encounters that met inclusion criteria, 100 received phenobarbital, compared with 187 that received benzodiazepines alone. Patients who received phenobarbital were provided significantly more lorazepam equivalents. There was a significant difference in the percentage of patient encounters that required admission to the hospital in the phenobarbital cohort compared with the benzodiazepine cohort (75% vs. 43.3%, p < 0.001). However, there was no difference in admission level of care to the floor (51.2% vs. 52.0%), stepdown (33.8% vs. 28%), or intensive care unit (15% vs. 20%), respectively. CONCLUSIONS: Patients who received phenobarbital for moderate alcohol withdrawal were more likely to be admitted to the hospital, but there was no difference in admission level of care when compared with patients who received benzodiazepines alone. Patients who received phenobarbital were provided greater lorazepam equivalents in the ED.

Is Phenobarbital an Effective Treatment for Alcohol Withdrawal Syndrome?

BACKGROUND: Alcohol use disorder is associated with a variety of complications, including alcohol withdrawal syndrome (AWS), which may occur in those who decrease or stop alcohol consumption suddenly. AWS is associated with a range of signs and symptoms, which are most commonly treated with GABAergic medications. CLINICAL QUESTION: Is phenobarbital an effective treatment for AWS? EVIDENCE REVIEW: Studies retrieved included two prospective, randomized, double-blind studies and three systematic reviews. These studies provided estimates of the effectiveness and safety of phenobarbital for treatment of AWS. CONCLUSIONS: Based on the available literature, phenobarbital is reasonable to consider for treatment of AWS. Clinicians must consider the individual patient, clinical situation, and comorbidities when selecting a medication for treatment of AWS.

Reliability and validity of the Estonian version of the Clinical Institute of Withdrawal Assessment for Alcohol scale.

AIMS: Our aim was to adapt the Clinical Institute of Withdrawal Assessment for Alcohol scale (CIWA-Ar) into Estonian and test its reliability and validity. METHODS: A total of 72 patients with alcohol withdrawal syndrome participated in the study. In order to assess the interrater reliability, at first assessment the CIWA-Ar was simultaneously completed by two nurses. In order to assess the sensitivity of the CIWA-Ar to the changes in the severity of the withdrawal syndrome, as well as its correlations to several indices characterizing the subjects' current condition, the CIWA-Ar, the Clinical Global Impression Severity subscale (CGI-S), the visual analogue scales for the assessment of the general feeling of malaise, anxiety and depression were filled in and the vital signs were measured at inclusion, in 4 h and after the withdrawal syndrome had been resolved. RESULTS: The intraclass correlation coefficient (ICC) for the Estonian version of the CIWA-Ar total score, used as an indicator of interrater reliability, was excellent. The CIWA-Ar had significant correlations with the psychiatrists' CGI-S ratings of the severity of the patient's condition at all assessment points. Significant correlations were also found between CIWA-Ar and patients' self-ratings, the highest correlations found with self-rated anxiety and general feeling of malaise. CIWA-Ar total score did not correlate with simultaneously measured heart rate, systolic and diastolic blood pressure at the first assessment. At the second assessment, heart rate had a significant correlation with the CIWA-Ar total score. CONCLUSION: Our study provides confirmation that the CIWA-Ar tool is well applicable in the Estonian language and culture setting.

Effectiveness of Gabapentin as a Benzodiazepine-Sparing Agent in Alcohol Withdrawal Syndrome.

Background and Objectives: Gabapentin has shown promise as a potential agent for the treatment of alcohol withdrawal syndrome. We aimed to evaluate the effectiveness of gabapentin as a benzodiazepine-sparing agent in patients undergoing alcohol withdrawal treatment in all the hospitals of a large tertiary healthcare system. Materials and Methods: Medical records of patients admitted to the hospital for alcohol withdrawal management between 1 January 2020 and 31 August 2022 were reviewed. Patients were divided into two cohorts: benzodiazepine-only treatment who received benzodiazepines as the primary pharmacotherapy and gabapentin adjunctive treatment who received gabapentin in addition to benzodiazepines. The outcomes assessed included the total benzodiazepine dosage administered during the treatment and the length of hospital stay. The statistical models were calibrated to account for various factors. Results: A total of 4364 patients were included in the final analysis. Among these, 79 patients (1.8%) received gabapentin in addition to benzodiazepines, and 4285 patients (98.2%) received benzodiazepines only. Patients administered gabapentin required significantly lower average cumulative benzodiazepine dosages, approximately 17.9% less, compared to those not receiving gabapentin (median 2 mg vs. 4 mg of lorazepam equivalent dose (p < 0.01)). However, there were no significant differences in outcomes between the two groups. Conclusions: Our findings demonstrate that using gabapentin with benzodiazepine was associated with a reduction in the cumulative benzodiazepine dosage for alcohol withdrawal. Considering gabapentin as an adjunctive therapy holds promise for patients with comorbidities who could benefit from reducing benzodiazepine dose. This strategy warrants further investigation.

Phenobarbital for the Management of Alcohol Withdrawal Syndrome in Critically Ill, Surgical-Trauma Patients.

INTRODUCTION: While benzodiazepines (BZD) are the standard of care therapy for the management alcohol withdrawal syndrome (AWS), phenobarbital (PHB) is often used as an alternative agent. The objective of this study is to assess the use of PHB therapy for the management of AWS in trauma-surgical intensive care unit (TSCU) patients. MATERIALS AND METHODS: This is an institutional review board-approved single-center, retrospective study conducted at a large academic medical center. Patients aged ≥ 18 y admitted to the TSCU receiving PHB therapy for primary management of AWS were included. The primary outcome evaluated was the incidence of AWS-related complications (AWSRC) defined as severe agitation, delirium tremens, or seizures following initiation of PHB. Secondary outcomes included the incidence of oversedation and duration of mechanical ventilation. RESULTS: Sixty patients were included in this study. AWSRC following initiation of PHB occurred in 65% of patients. Median time to initiation of PHB (42 versus 18 h, P = 0.001) and rates of oversedation (79.5% versus 28.6%, P < 0.001) were significantly greater among patients who experienced AWSRC compared to those who did not. Univariate analysis revealed use of BZD therapy for ≥ 24 h prior to PHB initiation, time from hospital admission to PHB initiation ≥ 24 h, presence of AWS symptoms at baseline, and baseline MINDS score > 6 were risk factors for AWSRC. CONCLUSIONS: Delays in initiation of PHB appear to be associated with an increased risk for developing AWSRC. Further research is needed to identify an optimal dosing strategy for TSCU patients at high risk for severe AWS.

Niche Roles for Dexmedetomidine in the Intensive Care Unit.

OBJECTIVE: Review dexmedetomidine use in critically ill patients for niche indications including sleep, delirium, alcohol withdrawal, sepsis, and immunomodulation. DATA SOURCES: Literature was sought using PubMed (February 2012-November 2022). Search terms included dexmedetomidine AND (hypnotics OR sedatives OR sleep OR delirium OR immunomodulation OR sepsis OR alcohol withdrawal). STUDY SELECTION AND DATA EXTRACTION: Relevant studies conducted in humans ≥18 years published in English were included. Exclusion criteria included systematic reviews, meta-analyses, and studies evaluating oral dexmedetomidine or other alpha-2 agonists. DATA SYNTHESIS: A total of 231 articles were retrieved. After removal of duplicates, title and abstract screening, and application of inclusion criteria, 35 articles were included. Across the clinical conditions included in this review, varying clinical outcomes were seen. Dexmedetomidine may improve morbidity outcomes in delirium, sleep, and alcohol withdrawal syndrome. Due to limited human studies and poor quality of evidence, no conclusions can be drawn regarding the role of dexmedetomidine in immunomodulation or sepsis. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review presents data for potential niche roles of dexmedetomidine aside from sedation in critically ill patients. This may serve as a guide for sedation selection in critically ill patients who may also benefit from the pleiotropic effects of dexmedetomidine due to a clinical condition discussed in this review. CONCLUSION: While further studies are needed, dexmedetomidine may provide benefit in other indications in critically ill patients including delirium, sleep, and alcohol withdrawal. Given the poor quality of evidence of dexmedetomidine use in immunomodulation and sepsis, no conclusions can be drawn.

Correlation Between and Nursing Satisfaction With CIWA-Ar, mMINDS, and SEWS Scoring Tools for the Assessment of Severe Alcohol Withdrawal Syndrome in ICU Patients.

BACKGROUND: Management of alcohol withdrawal syndrome (AWS) requires bedside assessments of symptom severity to guide therapies. Commonly used assessment tools are the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), the modified Minnesota Detoxification Scale (mMINDS) and the Severity of Ethanol Withdrawal Scale (SEWS). OBJECTIVE: To determine strength of correlation between the CIWA-Ar, mMINDS, and SEWS for bedside assessment of severe AWS and to survey nurses regarding ease of use of each tool. METHODS: A single-center prospective correlation study of the three assessment tools performed by bedside nurses on patients with AWS followed by a questionnaire assessing ease of use of each tool (1 being the easiest and 9 being the hardest). RESULTS: A total of 66 correlation assessments were performed by 49 nurses in 21 patients with AWS. Bedside CIWA-Ar, mMINDS, and SEWS were 14 ± 8.3, 13.9 ± 6.5, and 10.1 ± 4.5, respectively. The Pearson correlation coefficients were 0.814 (95% CI, 0.714-0.881) between CIWA-Ar and mMINDS; 0.722 (95% CI, 0.585-0.820) between CIWA-Ar and SEWS; and 0.658 (95% CI, 0.498-0.775) between SEWS and mMINDS. Nurse ratings for ease of use were 4 ± 2.3 for CIWA-Ar, 2.9 ± 2 for mMINDS (p=0.0044 vs. CIWA-Ar), and 4.8 ± 2.1 for SEWS (p=0.036 vs. CIWA-Ar, p<0.0001 vs. mMINDS). Forty-six (69.7%) respondents preferred mMINDS versus 14 (21.2%) and 6 (9.1%) respondents favored CIWA-Ar and SEWS, respectively. CONCLUSION: Correlations between the three scoring tools in severe AWS are robust. Only mMINDS was considered easy to use by nurses. It was the preferred tool.

Alcohol-related posterior reversible encephalopathy syndrome: a case report of a patient managed with a benzodiazepine-sparing regimen for alcohol withdrawal.

We report a case of posterior reversible encephalopathy syndrome (PRES) during treatment for alcohol withdrawal syndrome with gabapentin and clonidine. The patient developed severe hypertension, confusion and tremor, culminating in bilateral vision loss and a seizure. Imaging revealed posterior cerebral edema. Treatment with benzodiazepines, antihypertensives, and anti-seizure medications led to resolution. One year later, imaging showed resolution of the findings. We review the associated literature and propose the recognition of a PRES sub-entity, Alcohol-Related PRES (ARPRES), which can appear in the setting of alcohol withdrawal syndrome, chronic alcohol use, and acute alcohol intoxication, with or without hypertension.

Beyond benzodiazepines: a meta-analysis and narrative synthesis of the efficacy and safety of alternative options for alcohol withdrawal syndrome management.

PURPOSE: To compare the efficacy and safety of non-benzodiazepines (non-BZDs) to benzodiazepines (BZDs) in the treatment of alcohol withdrawal syndrome (AWS). METHODS: For relevant literature, Google Scholar, PubMed, Embase, OVID MEDLINE, EBSCO, Cochrane Central Registry of Controlled Trials, Web of Science, and Scopus were searched. Randomized control trials (RCTs) were included, omitted were nonblinded trials, blinded trials that were not randomized, and open-label studies. The Effective Public Health Practice Project Quality Assessment was used to assess the trial's quality. A meta-analysis and a narrative synthesis were carried out. RESULTS: Twenty non-BZDs and five BZDs were investigated in thirty RCTs. Meta-analysis favored gabapentin over chlordiazepoxide and lorazepam (d = 0.563, p < 0.001) and carbamazepine over oxazepam and lorazepam (d = 0.376, p = 0.029), for reducing Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale scores. Eleven non-BZDs fared better than BZDs for reducing CIWA-Ar, Total Severity Assessment, Selective Severity Assessment, Borg and Weinholdt, and Gross Rating Scale for Alcohol Withdrawal scores. Eight non-BZDs outmatched BZDs regarding autonomic, motor, awareness, and psychiatric symptoms. Sedation and fatigue were prevalent in BZDs, while seizures were prevalent in non-BZDs. CONCLUSION: For AWS treatments, non-BZDs are superior to or equally effective as BZDs. Non-BZD adverse events warrant further investigation. Agents that inhibit gated ion channels are promising candidates. PROTOCOL REGISTRATION: PROSPERO CRD42022384875.

Evaluation of Dexmedetomidine as an Adjunct to Phenobarbital for Alcohol Withdrawal in Critically Ill Patients.

INTRODUCTION: Dexmedetomidine (DEX) is commonly used with benzodiazepines for the management of alcohol withdrawal syndrome (AWS), but limited data exist regarding its use with phenobarbital (PHB). This analysis evaluated the utility of DEX in addition to PHB for AWS in adult patients admitted to the intensive care unit (ICU). METHODS: This was a single-center, retrospective cohort analysis of critically ill adult patients who received PHB plus either DEX or different adjunctive therapies (NO-DEX) for AWS between 2018 and 2021. Patients were excluded if they had underlying altered mental status or seizure disorder unrelated to AWS or received PHB at outside hospitals. Coarsened exact matching (CEM) was performed to match patients on baseline characteristics in a 1:1 ratio. The primary outcome was ICU length of stay (LOS). A multivariate linear regression analysis was performed to assess the effects of DEX on ICU LOS when accounting for confounders. Secondary outcomes included days with delirium and incidence of mechanical ventilation after PHB administration. RESULTS: Of the 606 encounters evaluated, 197 met criteria for inclusion. After CEM, 56 encounters remained in each group for analysis. The median ICU LOS was 97.2 [50.1:139.5] hours for the DEX group and 47.5 [28.8:88.1] hours for the NO-DEX group (P = .002). The multivariate linear regression analysis showed the use of DEX (P = .008) was independently associated with an increased ICU LOS by 49.8 h. The DEX group had higher rates of total delirium days (208 vs 143 days, P < .001) and a higher incidence of mechanical ventilation after PHB administration (32% vs 9%, P < .001). CONCLUSION: This analysis suggests the use of adjunctive DEX with PHB for AWS was associated with a prolonged ICU LOS. Additional studies are needed to further understand the role of adjunctive DEX in the treatment of AWS in critically ill patients.

Factors associated with discharge against medical advice in alcohol withdrawal patients.

This study aimed to examine characteristics associated with discharge against medical advice from the hospital in alcohol withdrawal patients, supporting the work of hospital staff and Alcohol Care Teams and identifying characteristics that may help target patients most likely to discharge against medical advice. We used Hospital Episode Statistics Data to identify demographic and clinical variables and compare these in alcohol withdrawal patients who discharged against medical advice from hospital, compared with those who were discharged by the clinical team. Factors significantly associated with alcohol withdrawal patients discharging against medical advice from hospital were: being admitted as an emergency; discharged on a weekend; living with no fixed abode; being male; being younger and having a shorter length of stay. This study identifies characteristics that can be used to support acute hospitals and Alcohol Care Teams, particularly in the allocation of resources to reduce discharges against medical advice and subsequent readmissions to the hospital. Particular consideration should be given to clinical provision in hospitals in emergency departments and on weekends, and also those patients who are admitted and are of no fixed abode.

Baclofen during alcohol detoxification reduces the need for additional diazepam: a randomized placebo-controlled trial.

Baclofen may reduce the symptoms of alcohol withdrawal, as an alternative or as an adjuvant for benzodiazepines, but the available data are insufficient to support baclofen-assisted alcohol withdrawal. This study investigated the need for diazepam during acute alcohol withdrawal in patients receiving baclofen. In a single-blind, dose-dependent randomized controlled trial with three study arms, 63 patients with alcohol use disorder, starting in-patient benzodiazepine-assisted alcohol detoxification, were randomly assigned to receive placebo (n = 18), baclofen 30 mg/day (N = 20), or baclofen 60 mg/day (N = 25) for 7 days. Diazepam was provided as needed based on the withdrawal symptoms stated by Clinical Institute Withdrawal Assessment for Alcohol-revised. The primary outcome measure was the number of patients in need of diazepam during alcohol detoxification. Secondary outcome measure included the between-group difference in the amount of diazepam needed during alcohol detoxification. Using baclofen 60 mg/day, 32% of patients needed additional diazepam compared to 35% on baclofen 30 mg/day and compared to 72% on placebo (P = .013). The median total amount of diazepam needed was significantly lower in patients receiving baclofen 60 mg/day (0 ± 10 mg diazepam) and baclofen 30 mg/day (0 ± 10 mg diazepam) compared to placebo (10 ± 43 mg diazepam; P = .017). Adverse events were comparable between patients on baclofen and placebo. Baclofen can reduce the withdrawal symptoms during alcohol detoxification. Baclofen was well tolerated and may be considered for the management of alcohol withdrawal syndrome, especially useful in situations where benzodiazepines should be withheld, such as patients with liver impairment.