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BACKGROUND: Alcohol withdrawal syndrome (AWS) presents with a complex spectrum of clinical manifestations that complicate postoperative management. In trauma setting, subjective screening for AWS remains challenging due to the criticality of injury in these patients. We thus identified several patient characteristics and perioperative outcomes associated AWS development. METHODS: The 2016-2020 National Inpatient Sample was queried to identify all non-elective adult (≥18 years) hospitalizations for blunt or penetrating trauma undergoing operative management with a diagnosis of AWS. Patients with traumatic brain injury or with a hospital duration of stay

The article focuses on alcohol withdrawal syndrome (AWS), a potentially life-threatening condition that occurs when individuals with alcohol use disorder (AUD) abruptly reduce or cease alcohol consumption. Topics include the clinical symptoms and pathophysiology of AWS, the importance of early recognition and assessment by healthcare professionals, and the role of neurotransmitters like glutamate and GABA in the development of withdrawal symptoms.

Background: Phenobarbital (PHB) has been shown to be an effective treatment of alcohol withdrawal syndrome (AWS), with multiple dosing strategies used (e.g., single-dose and symptom-triggered). Studies have often used tapered doses, typically following a front-loaded dose, despite PHB's long half-life which should lead to an ability to auto-taper. Objective: The purpose of this study was to compare clinical outcomes associated with two PHB dosing strategies (taper [T], no taper [NT]) for AWS. Methods: This retrospective cohort study compared adult patients admitted to the ICU from October 2017 to May 2019 who received an initial loading dose of PHB for AWS. The use of PHB was at the discretion of the clinician per our institutional guidelines. Prior to November 2018, patients were prescribed a PHB taper, while after this period, the taper was no longer recommended. The primary outcome was the proportion of patients requiring rescue PHB or adjunctive medications for AWS. Secondary outcomes included number of adjunctive agents used, prevalence of severe manifestations of AWS, ICU and hospital lengths of stay, and incidence of potentially significant drug interactions. Results: A total of 172 patients were included (T: n = 81, NT: n = 91). Baseline characteristics were similar between groups, including history of severe AWS and cumulative benzodiazepine dose pre-PHB. There was no difference in the primary outcome between groups (T: 70.4% vs NT: 59.3%, P = 0.152). The median number of adjunctive agents per patient, severe manifestations, and ICU and hospital length of stay did not differ between groups. Twenty-five patients (14.5%) had potentially significant drug interactions. Conclusion and Relevance: The use of a PHB loading dose without a taper may be comparable to a taper strategy on clinical outcomes. Prospective studies are needed to further delineate the optimal dose of PHB for AWS. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsDiscussionConclusionsAlcohol withdrawal is typically managed using benzodiazepines. However, modulation of both γ-aminobutyric acid-A and N-methyl-d-aspartate-receptors through ethanol provision may provide an alternative management strategy. This systematic review critically analyses the evidence surrounding the use of oral or intravenous ethanol for the management of alcohol withdrawal syndrome.Systematic searches of ProQuest – American Psychological Association, PsycInfo, MEDLINE and PubMed Central, Web of Science and Embase were performed (Prospero registration number: CRD42023425224). Search criteria were: Population = Patients receiving pharmacological interventions to treat or prevent alcohol withdrawal in a healthcare setting. Intervention = intravenous or enteral ethanol. Comparator = standard care, benzodiazepines, carbamazepine, adjunct medications including sedatives, or no comparator. Outcomes = complication rates, symptom scores, length of stay in healthcare settings. Exclusions were: preclinical studies, participants less than 18 years old, non-peer reviewed literature, poor study design or poor data quality. Study quality was assessed using an adapted National Institute for Health and Care Research quality tool. A narrative data synthesis approach was adopted.Eight thousand two hundred and four studies were retrieved. Ten were included in the final analysis. Overall study quality was poor. Seven studies reported treatment outcomes that were comparable to a control arm or in which ethanol conferred no detrimental effect. Three studies reported positive outcomes, and one study reported worse outcomes following ethanol administration.The review identified heterogeneity in study design and limited reporting surrounding patient demographics, patient alcohol use history and the practicalities of ethanol administration. As such, implementation of ethanol prescribing for the management of alcohol withdrawal is currently limited due to the quality and translatability of existing data surrounding its use.Further studies are required with more transparent and complete outcome reporting and practical implementation recommendations in order to facilitate the translation of ethanol prescribing for the management of alcohol withdrawal syndrome. [ABSTRACT FROM AUTHOR]

Background: Alcohol withdrawal is widely recognized as a trigger for acute symptomatic seizures among individuals with chronic alcohol consumption. While most alcohol withdrawal seizures occur shortly after cessation, chronic alcohol consumption can be associated with the development of epilepsy, necessitating anti‐epileptic drug (AED) therapy. This study aimed to investigate the clinical characteristics, seizure recurrence, and epilepsy development in patients with alcohol‐related seizures and to identify prognostic factors for epilepsy. Methods: In a retrospective analysis at Ewha Womans University Mokdong Hospital, 206 patients with alcohol‐related seizures were examined and 15 were excluded due to preexisting epilepsy. Demographic and clinical data, including alcohol withdrawal duration, seizure recurrence, types, and comorbidities, were investigated. Logistic regression models were used to analyze the risk factors for seizure recurrence and epilepsy development. The performance of the final models was evaluated based on the area under the receiver operating characteristic curve (AUC) and validated using calibration plots and leave‐one‐out cross‐validation. Results: Of the 191 patients (146 males; mean age 48.3 ± 12.1 years) with alcohol‐related seizures, 99 patients (51.8%) experienced seizure recurrence and 79 patients (41.4%) developed epilepsy. Factors associated with seizure recurrence included alcohol consumption levels, occurrence of focal impaired awareness seizure, anxiety, and headache. The number of recurrent seizures, semiology, status epilepticus, electroencephalogram findings, and brain imaging findings was associated with epilepsy development. The predictive models showed strong diagnostic performance, with AUCs of 0.833 for seizure recurrence and 0.939 for epilepsy development. Conclusion: High alcohol consumption and specific clinical and diagnostic features are significant predictors of seizure recurrence and the development of epilepsy among patients with alcohol‐related seizures. These findings underscore the importance of early identification and intervention to prevent seizure recurrence and the onset of epilepsy, emphasizing the importance of AED treatment in managing these conditions. [ABSTRACT FROM AUTHOR]

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. Is phenobarbital an effective treatment for AWS? 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. 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. [ABSTRACT FROM AUTHOR]

Background: Alcohol withdrawal syndrome (AWS) is highly prevalent in hospital inpatients. Recent evidence supports use of phenobarbital and gabapentin in certain patients, and screening tools for severe withdrawal risk can be used to guide care. Inpatients with AWS should also be considered for evidence-based treatment for alcohol use disorder (AUD). Purpose: The purpose of this quality improvement study was to monitor clinical outcomes and prescribing habits after updating an electronic order set for inpatient AWS management at a large, academic hospital. Methods: Protocol updates included use of the Prediction of Alcohol Withdrawal Severity Scale, phenobarbital and gabapentin protocols, and linkage to treatment resources. Data were collected for 10 months before and 14 months after implementation. Results: Intensive care unit (ICU) transfer rate decreased by 2.3%, whereas length of stay and readmissions were not significantly different. In patients treated with the order set, ICU transfer and length of stay outcomes were superior. Patients treated through the order set were more likely to receive evidence-based treatment for AWS and AUD. Conclusions: Electronic order sets can promote evidence-based practice for AWS. The updated protocol will remain in place at the study institution, with future efforts focused on education and ease of use to increase order set utilization. [ABSTRACT FROM AUTHOR]

The objective of this review was to evaluate the efficacy and safety of propofol in the treatment of critically ill patients diagnosed with alcohol withdrawal syndrome (AWS). A review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) criteria, and Embase, MEDLINE (PubMed), Cochrane CENTRAL, and Web of Science were queried for results through June 2024. Studies providing efficacy or safety data associated with propofol with a reported diagnosis of AWS in critically ill patients were included. Studies evaluating pediatric patients, those without quantitative and qualitative outcome data, and those not readily translatable to English were excluded. Five retrospective cohort analyses of 218 patients were included in this systematic review. Patients were found to have both significant and non‐significant increases in time to resolution of AWS symptoms when treated with propofol versus the AWS standard of care. Adjunct treatment with propofol was generally associated with reductions in total benzodiazepine use and increases in both ICU length of stay and duration of mechanical ventilation. The results of this systematic review provide the evidence necessary to support the use of propofol as an efficacious and safe medication in the management of severe and refractory AWS. Further investigation is required to determine optimal dosing strategies and durations of therapy. The results of this systematic review demonstrate the clinical utility of propofol as part of the management strategy for severe and refractory AWS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Patient-initiated discharges, also known as against medical advice discharges, are a common occurrence in inpatient withdrawal management settings. The purpose of this qualitative descriptive study was to gain an understanding of patient perspectives of their reasons for and experiences of patient-initiated discharge from an inpatient withdrawal management service. Methods: A consecutive sample of patients were recruited from an inpatient withdrawal management service. Qualitative descriptive methodology was used with semi-structured telephone interviews as the method of data collection. Interviews were transcribed and then analyzed following the principles of conventional content analysis. Results: Interviews were conducted with 13 participants. Factors that precipitated patient-initiated discharge were related to external pressures experienced by the patient, dissatisfaction with treatment or the hospital environment, and difficulties related to the COVID-19 pandemic. Participants often experienced strong emotions prior to leaving early and found conversations with staff about patient-initiated discharge difficult. Overall, participants had mixed perceptions of their discharge experience. Conclusions: This study is an important addition to the literature as the first to qualitatively examine patient perspectives of patient-initiated discharge from an inpatient withdrawal management service. Future studies should explore interventions to mitigate patient-initiated discharges or improve the associated processes when they cannot be avoided. [ABSTRACT FROM AUTHOR]

Background: Understanding the interplay between psychopathology of alcohol withdrawal syndrome (AWS) in alcohol use disorder (AUD) patients may improve the effectiveness of relapse interventions for AUD. Network theory of mental disorders assumes that mental disorders persist not of a common functional disorder, but from a sustained feedback loop between symptoms, thereby explaining the persistence of AWS and the high relapse rate of AUD. The current study aims to establish a network of AWS, identify its core symptoms and find the bridges between the symptoms which are intervention target to relieve the AWS and break the self-maintaining cycle of AUD. Methods: Graphical lasso networkwere constructed using psychological symptoms of 553 AUD patients. Global network structure, centrality indices, cluster coefficient, and bridge symptom were used to identify the core symptoms of the AWS network and the transmission pathways between different symptom clusters. Results: The results revealed that: (1) AWS constitutes a stable symptom network with a stability coefficient (CS) of 0.21-0.75. (2) Anger (Strength = 1.52) and hostility (Strength = 0.84) emerged as the core symptom in the AWS network with the highest centrality and low clustering coefficient. (3) Hostility mediates aggression and anxiety; anger mediates aggression and impulsivity in AWS network respectively. Conclusions: Anger and hostility may be considered the best intervention targets for researching and treating AWS. Hostility and anxiety, anger and impulsiveness are independent but related dimensions, suggesting that different neurobiological bases may be involved in withdrawal symptoms, which play a similar role in withdrawal syndrome. [ABSTRACT FROM AUTHOR]

Background: Risk factors for alcohol withdrawal delirium include heavy drinking, prior alcohol withdrawal delirium or convulsions, nondrug sedative use, and a history of tachycardia, withdrawal, and infections. Case Presentation: A 76‐year‐old man with a history of heavy drinking and type 2 diabetes was hospitalized for hypothermia, rhabdomyolysis, and acute renal failure after a typhoon. He developed alcohol withdrawal symptoms 24 h after his last drink, leading to severe withdrawal delirium characterized by restlessness, delusions, and altered consciousness. Treatment included lorazepam, in addition to comprehensive care for his physical condition. His condition fluctuated, especially at night, with his psychiatric symptoms exacerbated by his physical illnesses, suggesting delirium due to the coexistence of severe and multiple physical illnesses. After 44 days, following substantial improvements in both mental and physical health with perospirone, the patient was discharged. Conclusion: This case emphasizes the need for multidisciplinary collaboration in the treatment of such patients, especially during disasters, and the importance of long‐term monitoring for elderly patients with alcohol dependence syndrome after a disaster. [ABSTRACT FROM AUTHOR]

Alcohol withdrawal syndrome (AWS) is defined as the cessation or reduction in heavy and prolonged alcohol use within several hours to a few days of cessation. The recommended first-line therapy for AWS ranging from mild to severe or complicated remains benzodiazepines; in cases where benzodiazepines are not adequate in controlling persistent autonomic hyperactivity or anxiety, dexmedetomidine could be utilized. The possible advantage of dexmedetomidine compared to benzodiazepines is that it does not cause respiratory depression, thus reducing the risk of intubation and hospitalization in the ICUs, with the potential reduction in healthcare costs. The purpose of this systematic review and meta-analysis (PROSPERO CRD42018084370) is to evaluate the effectiveness and safety of dexmedetomidine as adjunctive therapy to the standard of care for the treatment of AWS. We retrieved literature from PubMed, EMBASE, and CENTRAL until 10 January 2024. Eligible studies were both randomized trials and nonrandomised studies with a control group, published in the English language and peer-reviewed journals. The primary outcome was tracheal intubation; secondary outcomes were (i) bradycardia and (ii) hypotension. A total of 3585 papers were retrieved: 2635 from EMBASE, 930 from Medline, and 20 from CENTRAL. After eliminating duplicates, 2960 papers were screened by title and abstract; 75 out of the 2960 papers were read in full text. The qualitative synthesis included nine of all manuscripts read in full text. The quantitative synthesis included eight studies for the primary outcome (tracheal intubation), seven for the secondary outcome bradycardia, and six for the secondary outcome hypotension. The meta-analysis showed that Dexmedetomidine, as adjunctive therapy, is not more effective than standard therapy in reducing the risk of tracheal intubation in AWS [RR: 0.57, 95% CI: 0.25–1.3, p = 0.15]. It also appears to be less safe than sedative therapy as it significantly increases the risk of bradycardia [RR: 2.68, 95% CI: 1.79–4.16, p = 0.0016]. Hypotension was not significantly different in patients who received dexmedetomidine [RR: 1.5, 95% CI: 0.69–3.49, p = 0.21]. [ABSTRACT FROM AUTHOR]

Alcohol consumption is an important risk factor for illness, disability, and mortality. Alcohol withdrawal symptoms have a significant health concern for individuals with alcohol dependence. This study aims to investigate the prevalence of withdrawal symptoms and liver function test abnormalities in this population and also to identify the factors associated with the severity of withdrawal symptoms. This cross-sectional study was conducted at a tertiary care facility involving 100 patients seeking treatment for alcohol dependence. Data collection included structured interviews and assessments using standardized scales and biochemical tests. Descriptive statistics, t-tests, and chi-square tests were employed to analyse the data. Individuals exhibiting mild/moderate alcohol withdrawal symptoms in this study displayed several distinctive features. They were more likely to have attained at least a high school education, their average alcohol consumption was notably lower, Importantly, their blood parameters, including RBC count, platelet count, total bilirubin levels, and liver enzyme levels (AST and ALT), generally exhibited fewer deviations from normal ranges. Family history of alcohol dependence and nicotine dependence was common among the participants. This research highlights the need for a holistic approach to address alcohol dependence, taking into consideration sociodemographic factors, clinical markers, and the diverse nature of this condition. The findings provide important insights for healthcare professionals to identify individuals at higher risk and guide treatment decisions. [ABSTRACT FROM AUTHOR]

The rising elderly population and the concomitant increase in alcohol consumption can result in a ground level fall (GLF). The purpose of this study is to evaluate the in-hospital mortality, hospital length of stay, and discharge disposition of elderly patients who sustained a ground level fall (GLF) and tested positive for an elevated blood alcohol concentration (BAC). The data of patients who were 65 years and older, had an injury after a GLF, and tested for BAC were accessed from the American College of Surgeon – Trauma Quality Improvement Program (ACS-TQIP) from the calendar years of 2011–2016. Patients' demography, injury, comorbidities, and outcomes were compared between the groups who tested positive (>0.08 g/dL) and negative (0 mg/dL) for BAC. Univariate, followed by matched analyses were performed. All p values are two-sided, and a p value < 0.05 is considered statistically significant. Out of 20,163 patients who satisfied the inclusion criteria, 2398 patients (∼12%) tested positive for an elevated BAC. There were significant differences found between the two groups, BAC-positive vs. BAC-negative, in univariate analysis for age and sex with p values < 0.001. Propensity score matching balanced demographic characteristics; however, differences remained in certain comorbidities. Exact matching balanced patient demography, injury, and comorbidities. The paired-matched analysis showed no significant differences between the two groups for in-hospital mortality (2.1% vs. 2.1%, p = 1) and median hospital length of stay (5[4–5] vs. 5[5–5], p = 0.307). A higher proportion of patients in the BAC group suffered from alcohol withdrawal syndrome (AWS) and deep vein thrombosis (DVT) complications (9.5% vs. 1.4%, p < 0.001 and 1.5% vs. 0.5%, p = 0.018) compared to BAC-negative patients. A slightly higher percentage of patients in the BAC-positive group were discharged home without any additional services (39.6% vs. 36.9%, p = 0.009). Of the elderly patients who sustained a GLF and tested for BAC, approximately 12% tested positive for BAC. The overall in-hospital mortality was 2.1%. The BAC-positive group suffered from higher complications of AWS and DVT, and more than 60% of patients required additional services at the time of discharge. • Of all elderly patients who had fallen from a ground level height and were tested for BAC, 12% of them tested positive. • Approximately 2% died and 43% of the patients were discharged to a skilled nursing facility. • Patients who tested positive for elevated BAC had significantly higher incidence of alcohol withdrawal syndrome and deep vein thrombosis complications. • Implementation of preventive measures can reduce mortality, morbidity, and the health care costs associated with an alcohol-related fall. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop clinical predictor tools for guiding the use of computed tomography (CT) head scans in non-traumatic Thai patients presented with seizure. A prediction model using a retrospective cross-sectional design was conducted. We recruited adult patients (aged ≥ 18 years) who had been diagnosed with seizures by their physicians and had undergone CT head scans for further investigation. Positive CT head defined as the presence of any new lesion that related to the patient's presented seizure officially reported by radiologist. A total of 9 candidate predictors were preselected. The prediction model was developed using a full multivariable logistic regression with backward stepwise elimination. We evaluated the model's predictive performance in terms of its discriminative ability and calibration via AuROC and calibration plot. The application was then constructed based on final model. A total of 362 patients were included into the analysis which comprising of 71 patients with positive CT head findings and 291 patients with normal results. Six final predictors were identified including: Glasgow coma scale, the presence of focal neurological deficit, history of malignancy, history of CVA, Epilepsy, and the presence of alcohol withdrawal symptom. In terms of discriminative ability, the final model demonstrated excellent performance (AuROC of 0.82 (95% CI: 0.76–0.87)). The calibration plot illustrated a good agreement between observed and predicted risks. This prediction model offers a reliable tool for effectively reduce unnecessary use and instill confidence in supporting physicians in determining the need for CT head scans in non-traumatic patients with seizures. [ABSTRACT FROM AUTHOR]

Prescribing of ethanol may be an alternative to benzodiazepines for managing alcohol withdrawal syndrome. We present our experience of oral ethanol prescribing within an acute United Kingdom National Health Service setting. A retrospective review of patients presenting with alcohol withdrawal who were managed with oral ethanol or benzodiazepines was performed from data collected across two acute care settings. Ethanol prescribing inclusion: high risk of delirium tremens, or a history of harmful alcohol consumption (typically ≥30 units/day; in which 1 unit = 8 grams of alcohol; one standard United States drink = 14 grams of alcohol) or known to have a history of severe alcohol withdrawal, alcohol-related seizures or delirium tremens. Inverse propensity score weighting was used to partially account for variance between the two patient populations. Fifty (82 per cent male; average age 50.9 years) and 93 (84 per cent male; average age 46.5 years) patients in receipt of benzodiazepines or ethanol, respectively, were included. The likelihood of hospital admission was significantly reduced when individuals were managed with ethanol (odds ratio 0.206 (95 per cent confidence interval; 0.066-0.641), Wald chi-square P = 0.006). In those not admitted, the treatment type had no significant impact on length of stay or the number of occasions a pharmacological agent was required. In those admitted, treatment had no significant effect on length of stay. We offer preliminary evidence to support a role of oral ethanol in the management of patients with alcohol withdrawal. We have implemented a robust and translatable guideline. Despite limitations in the data set the impact of ethanol in reducing the likelihood of admission remained significant. In individuals at significant risk of severe alcohol withdrawal, prescribing ethanol as part of a comprehensive care plan, may reduce unplanned admissions. The preliminary findings presented here warrant further assessment through prospective studies. [ABSTRACT FROM AUTHOR]

Antipsychotics are frequently used for inpatients with alcohol withdrawal syndromes (AWS). While there is evidence on the effects of these medications in other settings there is little data on the mortality rate associated with these drugs for the treatment of AWS) We utilized the national COSMOS Epic database to identify inpatients with AWS. We then assessed the mortality rate for adult patients with or without the use of anti-psychotics along with subsets of patients based on age, gender, race, and ethnicity. We identified 233,821 patients of whom 26% received antipsychotic agents. The mortality rate was 1.5%. Patients aged 60 or over and those who received typical antipsychotic agents had a higher mortality rate. The use of typical antipsychotic agents is associated with a higher mortality rate. The use of any antipsychotic agent in patients aged 60 or over is associated with an increased mortality rate. Further study of this effect is warranted. [ABSTRACT FROM AUTHOR]

Background: Millions of people struggle with alcohol use disorder (AUD). Abrupt abstinence after a period of chronic alcohol use can precipitate the alcohol withdrawal syndrome (AWS), which includes hyperexcitability and, potentially, seizures. We have shown that T‐type Ca2+ channels are novel, sensitive targets of alcohol, an effect that is dependent upon protein kinase C (PKC). The purpose of this study was to (1) understand midline thalamic neuronal hyperexcitability during alcohol withdrawal and its dependence on PKC; (2) characterize T channel functional changes using both current clamp and voltage clamp methods; and (3) determine which PKC isoform may be responsible for alcohol withdrawal (WD) effects. Methods: Whole‐cell patch clamp recordings were performed in midline thalamic neurons in brain slices prepared from C57bl/6 mice that underwent chronic intermittent alcohol exposure in a standard vapor chamber model. The recordings were compared to those from air‐exposed controls. T‐channel inactivation curves and burst responses were acquired through voltage‐clamp and current‐clamp recordings, respectively. Results: Whole‐cell voltage clamp recordings of native T‐type current exhibited a depolarizing shift in the voltage‐dependency of inactivation during alcohol withdrawal compared to air‐exposed controls. A PKCε translocation inhibitor peptide mitigated this change. Current clamp recordings demonstrated more spikes per burst during alcohol withdrawal. Consistent with voltage clamp findings, the PKCɛ translocation inhibitor peptide reduced the number of spikes per burst after WD. Conclusion: We found that alcohol WD produces T channel‐mediated hyperexcitability in the midline thalamus, produced in part by a shift in the inactivation curve consistent with greater availability of T current. WD effects on T current inactivation were reduced to control levels by blocking PKCε translocation. Our results demonstrate that PKCε translocation plays an important role in the regulation of alcohol withdrawal‐induced hyperexcitability in midline thalamic circuitry. [ABSTRACT FROM AUTHOR]

Background: Patients experiencing alcohol withdrawal often receive care on inpatient mental health units. Registered nurses on one such unit had several concerns and questions about the existing alcohol withdrawal symptom management order set. To address these issues, a multidisciplinary team including nurses, psychiatrists, and pharmacists was formed. Objectives: The aims for this project were to review and revise the existing order set, educate staff, implement the changes, and evaluate outcomes. Methods: The Plan–Do–Study–Act quality improvement framework guided the project. Five phases were completed to revise the order set and implement: a survey of nurses on the unit, community practice evaluation, and order set revisions. A simulation escape room facilitated nursing education. Patient records were reviewed to identify adverse events. Results: Diazepam replaced lorazepam as the primary medication choice, and a front-loading protocol was added. Order set clarity was improved, education increased nursing staff confidence to competently complete a patient assessment with the Clinical Institute Withdrawal Assessment Alcohol Scale Revised, and no adverse patient events occurred after implementation. Conclusion: A revised order set for symptom management of patients experiencing alcohol withdrawal reflected up-to-date evidence while maintaining patient safety. All nurses agreed the revised order set was clear and easy to follow; pharmacists and physicians were satisfied with the revisions. Implications for leaders include having a multidisciplinary team, sufficient resources to answer clinical questions, and regular discussions by all involved disciplines to review any adverse events as well as newly published evidence. Close monitoring of patients early in implementation is recommended to detect adverse events [ABSTRACT FROM AUTHOR]

ABSTRACTCurrently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to hospitals for consideration of withdrawal syndrome (AWS). However, only a fraction of those admitted will experience severe AWS. Previously, we and others have shown that epigenetic indices, such as the Alcohol T-Score (ATS), can quantify recent alcohol consumption. However, whether these or other alcohol biomarkers, such as carbohydrate deficient transferrin (CDT), could identify those at risk for severe AWS is unknown. To determine this, we first conducted genome-wide DNA methylation analyses of subjects entering and exiting alcohol treatment to identify loci whose methylation quickly reverted as a function of abstinence. We then tested whether methylation at a rapidly reverting locus, cg07375256, or other existing metrics including PAWSS scores, CDT levels, or ATS, could predict outcome in 125 subjects admitted for consideration of AWS. We found that PAWSS did not significantly predict severe AWS nor seizures. However, methylation at cg07375256 (ZSCAN25) and CDT strongly predicted severe AWS with ATS (p

Background: Alcohol withdrawal syndrome (AWS) presents with a complex spectrum of clinical manifestations that complicate postoperative management. In trauma setting, subjective screening for AWS remains challenging due to the criticality of injury in these patients. We thus identified several patient characteristics and perioperative outcomes associated AWS development. Methods: The 2016–2020 National Inpatient Sample was queried to identify all non-elective adult (≥18 years) hospitalizations for blunt or penetrating trauma undergoing operative management with a diagnosis of AWS. Patients with traumatic brain injury or with a hospital duration of stay

Abstract 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.

Abstract Objective Alcohol‐related seizures (ARS) are one of the most important consequences of alcohol withdrawal syndrome (AWS). However, demographic and clinical characteristics, and furthermore, the relationship of ARS with delirium tremens (DT), have not yet been evaluated in detail. Therefore, the aim of the present study was to reveal the correlates of ARS and examine the interaction of ARS with the occurrence of DT and with the severity of AWS. Methods In the retrospective study (Study 1) 2851 medical charts of inpatient admissions characterized by AWS and DT were listed. Demographic and clinical variables of ARS were assessed. In the follow‐up study (Study 2), patients admitted with AWS without (N = 28) and with (N = 18) ARS were enrolled. Study 1 was performed between 2008 and 2023, and Study 2 was performed in 2019 in Hungary. To determine the severity of AWS, the Clinical Institute Withdrawal Assessment Scale for Alcohol, Revised (CIWA‐Ar) was used. ARS is a provoked, occasional seizure; therefore, patients with epilepsy syndrome were excluded from the two studies. Statistical analyses were performed by the means of chi‐square tests, multinomial logistic regressions, mixed ANOVA, and derivation. Results The occurrence of DT, the history of ARS, and somatic co‐morbidities were found to be risk factors for the appearance of ARS. ARS was proved to be a risk factor for the development of DT. In the follow‐up study, there was no difference in the decrease of CIWA‐Ar scores between the groups. Significance Our present findings support the likelihood of kindling, which is one of the most important mechanisms underlying the development of ARS, but do not directly prove its presence. Additionally, our results revealed that the severity of AWS is not influenced by the presence of ARS. Plain Language Summary Provoked, occasional seizures during AWS are defined as ARS. In the present study, predictors and interactions of these seizures with DT—the most severe form of withdrawal—and with the severity of withdrawal were examined in retrospective and follow‐up studies. The present study shows that a history of withdrawal seizures, the occurrence of DT, and somatic comorbidities are predictors of the development of seizures. Furthermore, our findings suggest that the presence of seizures does not influence the severity of withdrawal.

Background: Alcohol use disorder (AUD) is related to mental and somatic disorders that result in alcohol withdrawal syndrome (AWS), with 30% of AWS cases leading to life-threatening delirium tremens (DTs). Currently, studies do not support using any one biomarker in DTs. Neurotrophins affect neuromodulation, playing a role in the pathogenesis of AUD, AWS, and DTs. Methods: This review aims to summarize experimental and clinical data related to neurotrophins and S100B in neuroplasticity, as well as neurodegeneration in the context of AUD, AWS, and DTs. This work used publications that were selected based on the protocol consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Results: The BDNF level could be a good candidate biomarker for relapse susceptibility, as it is significantly reduced during consumption and gradually increases during abstinence. GDNF influences AUD through its integral role in the function of dopaminergic neurons and ablates the return to alcohol-drinking behavior. NGF protects neurons from ethanol-induced cytotoxic damage and affects recovery from cognitive deficits after brain damage. The NT-3 level is decreased after alcohol exposure and is involved in compensatory mechanisms for cognitive decline in AUD. NT-4 affects oxidative stress, which is associated with chronic alcohol consumption. S100B is used as a biomarker of brain damage, with elevated levels in serum in AUD, and can protect 5-HT neurons from the damage caused by alcohol. Conclusions: BDNF, GDNF, NT-3, NT-4, NGF, and S100B may be valuable markers for withdrawal syndrome. In particular, the most relevant is their association with the development of delirium complications. However, there are few data concerning some neurotrophins in AWS and DTs, suggesting the need for further research. [ABSTRACT FROM AUTHOR]

Background: Alcohol use is frequent in trauma patients and alcohol withdrawal syndrome (AWS) is associated with significant morbidity. Benzodiazepines are commonly used for AWS, but may cause neurologic and respiratory adverse events (AEs). The objective was to evaluate the effectiveness and safety of a phenobarbital-based protocol for the treatment of AWS in non-intensive care unit (ICU) trauma patients. Methods: Adult non-ICU trauma patients at high risk of or experiencing AWS PRE and POST implementation of a phenobarbital-based protocol were included. Outcomes were AWS-related complications (AWS-RC), benzodiazepine use, adjunctive medication use, hospital length of stay (HLOS), and medication-related AEs. Subgroup analyses were performed on patients with traumatic brain injury (TBI), rib fractures, and at high risk of severe AWS. Results: Overall, 110 patients were included (51 PRE, 59 POST). AWS-RC developed in 17 PRE patients compared to 10 POST patients (33% vs 17%; P =.05). PRE patients were more likely to receive benzodiazepines (88% vs 42%, P <.0001) and higher total dose (11 vs 4 mg lorazepam equivalent; P =.001). No difference noted in HLOS (8 vs 8 days, P =.27), adjunctive medication use (49% vs 54%, P =.60), or AEs (57% vs 39%, P =.06). There was no difference in AWS-RC in the TBI subgroup (P =.19), less AEs in the rib fracture POST subgroup (P =.04), and less AWS-RC in the high risk of severe AWS POST subgroup (P =.03). Discussion: A phenobarbital-based protocol in trauma patients is effective in preventing AWS-RC and decreasing benzodiazepine use without increasing AEs. [ABSTRACT FROM AUTHOR]

Background: Anticonvulsant prophylaxis (ACP) for early post-traumatic seizures (PTS) is recommended in patients with traumatic brain injury (TBI). Phenobarbital (PB) may be used to prevent alcohol withdrawal syndrome (AWS) in at-risk patients. The dual-purpose use of PB in the TBI population would allow for consolidation of pharmacotherapy. Objective: The primary objective of this study was to determine the frequency of early PTS in TBI patients at risk of AWS treated with PB as ACP. Secondary objectives included determining rates of over sedation and endotracheal intubation. Methods: Patients received an intravenous (IV) loading dose of PB at 15-20 mg/kg followed by 1 mg/kg every 12 hours for 7 days with a goal level of 15-20 mcg/mL. Medication data, seizure frequency, and episodes of over sedation and endotracheal intubation were collected. Results: Eighty patients were treated with PB over a 1-year period. Thirty-nine patients were analyzed. Median loading dose was 19.9 (Interquartile Range 19.1-20.0) mg/kg with a median post load level of 21.7 mcg/mL (IQR 18.3-25.8) mcg/mL. One patient (2.6%) had electrographic evidence for early PTS. PB was discontinued in 4 (10.3%) patients out of concern for over sedation. One patient required endotracheal intubation after rapid PB loading. Conclusion: The frequency of early PTS was low when PB was used as primary ACP in patients with TBI at risk for AWS. Over sedation is a potential adverse effect that should be considered in the choice of ACP. No conclusions can be drawn as to the effectiveness of PB in preventing AWS. [ABSTRACT FROM AUTHOR]

Alcoholism presents a significant health concern with notable socioeconomic implications. Alcohol withdrawal syndrome (AWS) can manifest when individuals cease or drastically reduce their alcohol consumption after prolonged use. Non-alcoholic fatty liver disease (NAFLD) is characterized by substantial lipid accumulation in the liver cells of individuals with no history of alcohol consumption. There is evidence suggesting an association between cognitive impairment and both conditions. This study aimed to evaluate cognitive impairment in patients with NAFLD and AWS using the Mini-Mental State Examination (MMSE). This study involved 120 patients admitted to two hospitals in Craiova, Romania. Results indicated that patients with NAFLD did not exhibit cognitive impairment as measured by MMSE (Mean = 29.27, SD = 0.785). Conversely, patients with AWS showed more pronounced cognitive dysfunction, with a mean MMSE score at admission of 16.60 ± 4.097 and 24.60 ± 2.832 after 2 weeks under treatment with Vitamins B1 and B6 and Cerebrolysin. Additionally, our findings suggested that cognitive dysfunction among alcohol consumers was correlated with the severity of clinical symptoms, as demonstrated by the severity of tremors in our study. The two-week period under treatment and alcohol withdrawal was insufficient for cognitive function to return to normal levels. Observational studies on longer periods of time are advised. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Delirium Tremens (DT) is known to be a serious complication of alcohol withdrawal syndrome (AWS). Neurotransmitter abnormalities, inflammation, and increased permeability are associated with the pathogenesis of AWS and DT. However, the biomarkers of these conditions are still poorly understood. Methods: In this work, biochemical, hematologic, inflammatory, and gut permeability biomarkers were investigated in the following three groups: healthy controls (n = 75), severe AWS patients with DT (n = 28), and mild/moderate AWS without DT (n = 97). Blood sampling was performed after resolution of the acute condition (on 5 ± 1 day after admission) to collect clinical information from patients and to investigate associations with clinical scales. Biomarker analysis was performed using automated analyzers and ELISA. Inflammatory biomarkers included the erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), and platelet-to-lymphocyte ratio (PLR). Results: Among the biochemical biomarkers, only glucose, total cholesterol, and alanine aminotransferase (ALT) changed significantly in the analyzed groups. A multiple regression analysis showed that age and ALT were independent predictors of the CIWA-Ar score. Hematologic biomarker analysis showed an increased white blood cell count, and the elevated size and greater size variability of red blood cells and platelets (MCV, RDWc, and PDWc) in two groups of patients. Gut permeability biomarkers (FABP2, LBP, and zonulin) did not change, but were associated with comorbid pathologies (alcohol liver disease and pancreatitis). The increase in inflammatory biomarkers (ESR and PLR) was more evident in AWS patients with DT. Cluster analysis confirmed the existence of a subgroup of patients with evidence of high inflammation, and such a subgroup was more frequent in DT patients. Conclusions: These findings contribute to the understanding of biomarker variability in AWS patients with and without DT and support the heterogeneity of patients by the level of inflammation. [ABSTRACT FROM AUTHOR]

Our aim was to adapt the Clinical Institute of Withdrawal Assessment for Alcohol scale (CIWA-Ar) into Estonian and test its reliability and validity. 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. 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. Our study provides confirmation that the CIWA-Ar tool is well applicable in the Estonian language and culture setting. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) and chronic pain disorders are pervasive, multifaceted medical conditions that often co-occur. However, their comorbidity is often overlooked, despite its prevalence and clinical relevance. Individuals with AUD are more likely to experience chronic pain than the general population. Conversely, individuals with chronic pain commonly alleviate their pain with alcohol, which may escalate into AUD. This narrative review discusses the intricate relationship between AUD and chronic pain. Based on the literature available, the authors present a theoretical model explaining the reciprocal relationship between AUD and chronic pain across alcohol intoxication and withdrawal. They propose that the use of alcohol for analgesia rapidly gives way to acute tolerance, triggering the need for higher levels of alcohol consumption. Attempts at abstinence lead to alcohol withdrawal syndrome and hyperalgesia, increasing the risk of relapse. Chronic neurobiological changes lead to preoccupation with pain and cravings for alcohol, further entrenching both conditions. To stimulate research in this area, the authors review methodologies to improve the assessment of pain in AUD studies, including self-report and psychophysical methods. Further, they discuss pharmacotherapies and psychotherapies that may target both conditions, potentially improving both AUD and chronic pain outcomes simultaneously. Finally, the authors emphasize the need to manage both conditions concurrently, and encourage both the scientific community and clinicians to ensure that these intertwined conditions are not overlooked given their clinical significance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Studies on early abstinence suggest that cognitive function is significantly reduced in the first year of abstinence, which raises the question of whether it is relevant to early relapse in patients with substance use disorders. This study investigates the extent to which impairments in executive function and memory predict alcohol relapse in patients with alcohol use disorder (AUD). Understanding these relationships is crucial for improving therapeutic approaches to prevent relapse in patients with AUD. Methods: We selected 116 adult patients (79 male and 37 female) diagnosed with AUD based on DSM‐5 criteria, all of whom were undergoing alcohol detoxification treatment. A comprehensive array of neuropsychological tests was administered to assess global cognition, memory, and executive functions. Patients' alcohol use was monitored monthly during a 6‐month follow‐up period. Logistic regression and Cox regression were used to explore the relationship between cognitive function and the likelihood of alcohol relapse. Results: Impairments in global cognition, semantic and phonemic fluency, cognitive flexibility, and learning ability during detoxification were significant predictors of relapse in AUD patients, showing similar predictive values at both 3 and 6 months post‐treatment. An abnormal Montreal Cognitive Assessment (MoCA) score increased the risk of relapse by 123% (HR: 2.227), and impairments in both semantic and phonemic fluency each increased the risk by 142% (HR: 2.423). Additionally, abnormal performance on the MoCA, Trail Making Test Part B (TMT‐B), and California Verbal Learning Test (CVLT) was associated with a higher number of drinking days at 3 months (IRR: 3.764; IRR: 2.237; IRR: 2.738, respectively) and abnormal MoCA and TMT‐B scores at 6 months (IRR: 2.451; IRR: 1.859, respectively). Conclusions: The MoCA test is a valuable tool for predicting relapse risk in AUD patients undergoing detoxification treatment, with similar predictive value for relapse at 3 or 6 months. Learning ability needs to be assessed and their impairments considered in the treatment of AUD patients. Future research should explore strategies for managing patients with impairments in memory and learning ability to enhance treatment effectiveness and prevent relapse. [ABSTRACT FROM AUTHOR]

Concern about adverse effects from phenobarbital limits its use in treating alcohol withdrawal syndrome (AWS) on general medical wards. Benzodiazepines are the recommended treatment for inpatient management of AWS, yet a subset of patients have an inadequate response or experience complications of AWS despite treatment with benzodiazepines. Data supporting an alternative treatment are needed. We set out to estimate the rate of serious adverse events (SAEs) of phenobarbital treatment for AWS on general medical wards. Retrospective cohort study of all general medical ward patients hospitalized at a single tertiary urban VA Medical Center from October 2018–May 2021 who received phenobarbital for treatment of AWS. Primary outcomes were SAEs attributed to phenobarbital and treatment failure. SAEs were defined as ICU transfer or intubation for over-sedation, pneumonia, and death. Treatment failure was defined as progression of withdrawal resulting in seizure, ICU transfer, behavioral emergencies, or death. During the study period, phenobarbital was administered in 29% (244) of all AWS hospitalizations. Among them, 93% had a history of AWS hospitalization and 68% had a history of complicated AWS. Fifty-three percent of patients met criteria for moderate, severe, or complicated withdrawal prior to phenobarbital initiation. The mean cumulative dose of phenobarbital per patient was 966.5 mg (13.6 mg/kg). SAEs occurred in 1 of 244 hospitalizations (0.4%): there were no intubations, ICU transfers for oversedation, or deaths due to phenobarbital or AWS. One case of pneumonia was possibly attributable to phenobarbital. Treatment failures (6 ICU transfers, 9 behavioral emergencies) were identified during 12 of 244 hospitalizations (4.9%). SAEs and treatment failures were infrequent among 148 patients treated with phenobarbital across 244 hospitalizations with a mean cumulative dose of 966.5 mg per patient. Our findings suggest that phenobarbital is a safe alternative treatment of AWS in general medical ward patients. • There were no seizures, deaths, or intubations in patients treated with phenobarbital for alcohol withdrawal. • Nearly 70% of the cohort had a history of severe, complicated alcohol withdrawal. • Transfer to the ICU occurred in only 2.5% of hospitalizations treated with phenobarbital. • Adjunctive medication use for symptom management was high (53% of cohort). [ABSTRACT FROM AUTHOR]

The fourth Society for Academic Emergency Medicine (SAEM) Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE‐4) is on the topic of the emergency department (ED) management of nonopioid use disorders and focuses on alcohol withdrawal syndrome (AWS), alcohol use disorder (AUD), and cannabinoid hyperemesis syndrome (CHS). The SAEM GRACE‐4 Writing Team, composed of emergency physicians and experts in addiction medicine and patients with lived experience, applied the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach to assess the certainty of evidence and strength of recommendations regarding six priority questions for adult ED patients with AWS, AUD, and CHS. The SAEM GRACE‐4 Writing Team reached the following recommendations: (1) in adult ED patients (over the age of 18) with moderate to severe AWS who are being admitted to hospital, we suggest using phenobarbital in addition to benzodiazepines compared to using benzodiazepines alone [low to very low certainty of evidence]; (2) in adult ED patients (over the age of 18) with AUD who desire alcohol cessation, we suggest a prescription for one anticraving medication [very low certainty of evidence]; (2a) in adult ED patients (over the age of 18) with AUD, we suggest naltrexone (compared to no prescription) to prevent return to heavy drinking [low certainty of evidence]; (2b) in adult ED patients (over the age of 18) with AUD and contraindications to naltrexone, we suggest acamprosate (compared to no prescription) to prevent return to heavy drinking and/or to reduce heavy drinking [low certainty of evidence]; (2c) in adult ED patients (over the age of 18) with AUD, we suggest gabapentin (compared to no prescription) for the management of AUD to reduce heavy drinking days and improve alcohol withdrawal symptoms [very low certainty of evidence]; (3a) in adult ED patients (over the age of 18) presenting to the ED with CHS we suggest the use of haloperidol or droperidol (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence]; and (3b) in adult ED patients (over the age of 18) presenting to the ED with CHS, we also suggest offering the use of topical capsaicin (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence]. [ABSTRACT FROM AUTHOR]

Objective: Despite frequent treatment of alcohol withdrawal syndrome (AWS) in the emergency department (ED), evidence for phenobarbital (PB) as an ED alternative therapy is mixed. We conducted a systematic review and meta‐analysis comparing safety and efficacy of PB to benzodiazepines (BZDs) for treatment of AWS in the ED. Methods: We searched articles and references published in English in PubMed, Web of Science, and Embase from inception through May 2022. We included randomized trials and cohort studies comparing treatment with PB to BZD controls and excluded studies focused on non‐AWS conditions. Review was conducted by two blinded investigators and a third author; eight of 59 (13.6%) abstracts met inclusion criteria for review and meta‐analysis using a random‐effects model. Treatment superiority was evaluated through utilization, pharmacologic, and clinical outcomes. Primary outcomes for meta‐analysis were the proportion of patients (1) admitted to the intensive care unit (ICU), (2) admitted to the hospital, (3) readmitted to the ED after discharge, and (4) who experienced adverse events. Results: Eight studies (two randomized controlled trials, six retrospective cohorts) comprised data from 1507 patients in 2012 treatment encounters for AWS. All studies were included in meta‐analysis for adverse events, seven for hospital admission, five for ICU admission, and three for readmission to the ED after discharge. Overall methodological quality was low‐moderate, risk of bias moderate‐high, and statistical heterogeneity moderate. Pooled relative risk of ICU admission for those treated with PB versus BZD was 0.92 (95% confidence interval [CI] 0.54–1.55). Risk for admission to the hospital was 0.98 (95% CI 0.89–1.07) and for any adverse event was 1.1 (95% CI 0.78–1.57); heterogeneity prevented meta‐analysis for ED readmission. Conclusions: The current literature base does not show that treatment with PB significantly reduces ICU admissions, hospital admissions, ED readmissions, or adverse events in ED patients with AWS compared with BZDs alone. [ABSTRACT FROM AUTHOR]

Objectives: Alcohol withdrawal syndrome (AWS) is a commonly presenting condition in the emergency department (ED) and can have severe complications, including mortality. Benzodiazepines are first‐line medications for treating AWS but may be unavailable or insufficient. This systematic review evaluates the direct evidence assessing the utility of phenobarbital for treating AWS in the ED. Methods: A systematic search was conducted and designed according to the patient–intervention–comparator–outcome (PICO) question: (P) adults (≥18 years old) presenting to the ED with alcohol withdrawal; (I) phenobarbital (including adjunctive); (C) benzodiazepines or no intervention; and (O) AWS complications, admission to a monitored setting, control of symptoms, adverse effects, and adjunctive medications. Two reviewers independently assessed articles for inclusion and conducted risk of bias assessments for included studies. Results: From 70 potentially relevant articles, seven studies met inclusion criteria: three retrospective cohort studies, two retrospective chart reviews, and two randomized controlled trials (RCTs), one examining phenobarbital monotherapy and one examining adjunctive phenobarbital. Across the retrospective cohort studies, treatment of AWS with phenobarbital resulted in lower odds of a subsequent ED visit. The retrospective chart reviews indicated that phenobarbital was associated with higher discharge rate compared to benzodiazepine‐only treatments. For the two RCTs, phenobarbital did not differ significantly from benzodiazepine for most outcomes, although concomitant treatment with phenobarbital was associated with lower benzodiazepine use and intensive care unit admission. The heterogeneous designs and small number of studies prevented quantitative synthesis. Conclusions: Relatively few studies provide direct evidence on the utility of phenobarbital for AWS in the ED, but the evidence that exists generally suggests that it is a reasonable and appropriate approach. Additional RCTs and other methodologically rigorous investigations are needed for more definitive direct evidence. [ABSTRACT FROM AUTHOR]

Background: Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies. Objectives: The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS). Methods: Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment. Results: A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01). Conclusion and Relevance: DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability. [ABSTRACT FROM AUTHOR]

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Objective: Alcohol‐related seizures (ARS) are one of the most important consequences of alcohol withdrawal syndrome (AWS). However, demographic and clinical characteristics, and furthermore, the relationship of ARS with delirium tremens (DT), have not yet been evaluated in detail. Therefore, the aim of the present study was to reveal the correlates of ARS and examine the interaction of ARS with the occurrence of DT and with the severity of AWS. Methods: In the retrospective study (Study 1) 2851 medical charts of inpatient admissions characterized by AWS and DT were listed. Demographic and clinical variables of ARS were assessed. In the follow‐up study (Study 2), patients admitted with AWS without (N = 28) and with (N = 18) ARS were enrolled. Study 1 was performed between 2008 and 2023, and Study 2 was performed in 2019 in Hungary. To determine the severity of AWS, the Clinical Institute Withdrawal Assessment Scale for Alcohol, Revised (CIWA‐Ar) was used. ARS is a provoked, occasional seizure; therefore, patients with epilepsy syndrome were excluded from the two studies. Statistical analyses were performed by the means of chi‐square tests, multinomial logistic regressions, mixed ANOVA, and derivation. Results: The occurrence of DT, the history of ARS, and somatic co‐morbidities were found to be risk factors for the appearance of ARS. ARS was proved to be a risk factor for the development of DT. In the follow‐up study, there was no difference in the decrease of CIWA‐Ar scores between the groups. Significance: Our present findings support the likelihood of kindling, which is one of the most important mechanisms underlying the development of ARS, but do not directly prove its presence. Additionally, our results revealed that the severity of AWS is not influenced by the presence of ARS. Plain Language Summary: Provoked, occasional seizures during AWS are defined as ARS. In the present study, predictors and interactions of these seizures with DT—the most severe form of withdrawal—and with the severity of withdrawal were examined in retrospective and follow‐up studies. The present study shows that a history of withdrawal seizures, the occurrence of DT, and somatic comorbidities are predictors of the development of seizures. Furthermore, our findings suggest that the presence of seizures does not influence the severity of withdrawal. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol Use Disorder (AUD) is a significant medical condition characterized by an inability to control alcohol use despite adverse consequences, ranging from occasional excessive drinking to daily dependency. Treatment for AUD involves a combination of pharmacological and behavioral approaches. Common medications include Disulfiram, Naltrexone, and Acamprosate, with newer therapies like gabapentin providing additional options. This review aims to systematically evaluate and synthesize available research concerning the use of gabapentin in the treatment of AUD. Methods: This review was created based on 4 articles found in PubMed and Pubmed database based on keywords: "alcohol use disorder", "gabapentine in alcohol use disorder" and "gabapentine". State of knowledge: Gabapentin was originally developed for its anticonvulsant properties and tts primary use was to treat epilepsy by reducing the frequency of seizures in patients with refractory epilepsy. Gabapentin’s effectiveness in treating Alcohol Use Disorder is founded on its ability to modulate neuronal excitability. Recent RCTs have demonstrated the efficacy of gabapentin in alcohol use disorder, especially for patients with a history of significant alcohol withdrawal symptoms, though the extended-release formulation of gabapentin proved ineffective. Conculsions: The overall findings suggest gabapentin holds promise as a treatment for AUD, particularly in individuals with significant withdrawal symptoms, but additional studies are required to fully establish its efficacy and optimal use.

Alcohol withdrawal syndrome (AWS) is a complex set of symptoms that occur in alcohol-dependent individuals after sudden withdrawal or a significant reduction in alcohol consumption. AWS symptoms occur in about 50% of alcohol abusers. These symptoms may include restlessness, tremor, nausea, nervousness, tachycardia, elevated blood pressure, hyperhidrosis, insomnia, hyperactivity, and hallucinations. In some cases, seizures may occur and delirium tremens may develop, which is life-threatening and an absolute indication for hospitalization of the patient. Effective treatment of AWS is the key to prevent complications and to reduce the risk of death. Treatment of alcohol withdrawal syndrome requires a complex approach that combines properly performed diagnosis, careful monitoring of the patient's condition, pharmacotherapy, equalization of electrolyte disorders, adequate hydration of the patient, supplementation of thiamine deficiencies and, in the case of symptoms of alcoholic delirium, intensive medical care. Pharmacological treatment plays a key role, with the first line of treatment being benzodiazepines, which reduce the risk of epileptic seizures and delirium tremens, and reduce mortality in the course of AWS. Individualized therapy adjustment and patient monitoring are crucial to ensure effective and safe treatment.

There is research using craving reduction as a measure of recovery from drug addiction, as recently reported at the College on Problems of Drug Dependence (CPDD) from National Institute on Drug Abuse (NIDA) researchers. We wanted to find out whether craving reduction can also be used as a measure of recovery from alcohol use disorder (AUD). So, we asked George F. Koob, Ph.D., director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), who, with Laura E. Kwako, Ph.D., chief of NIAAA's treatment, health services, and recovery branch, responded to our questions. [ABSTRACT FROM AUTHOR]

Background and Objectives Methods Results Discussion and Conclusions Scientific Significance Benzodiazepines are the primary method of treatment of alcohol withdrawal, though the American Society of Addiction Medicine guidelines also include alternative agents for consideration. Observations in a Department of Veterans Affairs (VA) psychiatric emergency room noted consistent benzodiazepine use with an overall lack of use of alternative agents, even with low Clinical Institute Withdrawal Assessment for Alcohol (CIWA) scores and in the absence of other concerning symptoms. Due to concerns of potential more‐than‐necessary benzodiazepine use, we analyzed adjunctive clonidine use for elevated blood pressure/pulse in alcohol withdrawal among this Veteran population.This is a single‐site VA retrospective chart review of the psychiatric emergency room from July 1, 2022, to June 30, 2023, focused on patients with alcohol withdrawal managed on a CIWA protocol. Excluding concurrent opioid withdrawal and clonidine as home medication, 167 patient charts were analyzed for this study.Among 167 patients, 99 (59.3%) had comorbid hypertension. A total of 614 medication doses were given for elevated CIWA (373, 60.8%) and elevated blood pressure/pulse (241, 39.2%). Of the 241 doses for elevated blood pressure/pulse, only 2.5% were clonidine. Among all benzodiazepine doses, 75.3% were given to patients with comorbid hypertension. Clonidine was administered to 3.0% of patients, making up 2.5% of total dosing.Alcohol withdrawal management lacks optimization. Integrating adjunctive medications could reduce potential benzodiazepine overuse effectively addressing elevated blood pressure/pulse.This study sheds light on the potential underutilization of clonidine and its potential role in improving alcohol withdrawal syndrome management. By addressing elevated blood pressure/pulse and curbing potential overuse of benzodiazepines, it may contribute to further optimizing patient care. [ABSTRACT FROM AUTHOR]