Beyond the Liver: Neurologic Manifestations of Alcohol Use.

Alcohol use, while commonly associated with liver damage, also has significant neurologic implications, which often mimic hepatic encephalopathy and complicate diagnosis and management. Alcohol mediates its acute central nervous system effects by altering neurotransmitter balance, notably between gamma-aminobutyric acid and glutamate. Its chronic neurotoxicity, compounded by thiamine deficiency, results in chronic neurologic complications. Clinically, alcohol-related neurologic disorders present a spectrum from acute intoxication and withdrawal to chronic conditions like Korsakoff syndrome, dementia, cerebellar degeneration, and peripheral neuropathy. This review underscores differentiating these conditions from hepatic encephalopathy and highlights the importance of history-taking and physical examination in clinical practice.

The Role of Propofol in Alcohol Withdrawal Syndrome: A Systematic Review.

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.

Dexmedetomidine as Adjunctive Therapy for the Treatment of Alcohol Withdrawal Syndrome: A Systematic Review and Meta-Analysis.

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].

Exploring core symptoms of alcohol withdrawal syndrome in alcohol use disorder patients: a network analysis approach.

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 network were 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.

Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal in the Medical Intensive Care Unit (ICU): A Retrospective Cohort Study.

Background: Phenobarbital (PHB) is a safe and efficacious alternative to benzodiazepines (BZD) for treating severe alcohol withdrawal (AWS). However, the safety of utilizing PHB for patients initially treated with BZD is unknown. Objective: To evaluate the safety and efficacy of PBH compared to BZDs in severe AWS in the medical intensive care unit (ICU). Methods: This was a retrospective cohort study comparing critically ill patients admitted for AWS who received BZDs or PHB. The primary outcome was time to persistent resolution of altered mentation. Secondary outcomes included development and duration of delirium, need for mechanical ventilation, development of withdrawal seizures, and ICU and hospital length of stay. Results: Ninety-five patients were evaluated (53 in PHB group, 42 in BZD group). Before study medication, less BZD patients demonstrated abnormal mentation compared with PHB patients (RASS < -2: 2.39% vsvs. 28.12%, respectively, and RASS > +2: 9.9% vsvs. 48.76%; P <0.001 for both). No difference was seen between groups for the primary outcome (1.8 hours for BZD cohort vsvs. 13.81 hours for PHB cohort; P =0.22). More patients in the BZD cohort developed a seizure after study medication administration (5.67% vs 0%, respectively; P =0.02). No significant difference was seen in other secondary outcomes. Conclusions: This study provides support for use of PHB after BZD if patients remain in uncontrolled withdrawal. Despite significant doses of BZDs before PHB, patients in the PHB cohort demonstrated similar clinical and safety outcomes compared to BZD alone.

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.

Real-world analysis on the use of gamma-hydroxybutyric acid for alcohol withdrawal syndrome in hospitalized patients with diagnosis of cirrhosis.

The present real-world analysis aimed to evaluate and describe the use of gamma-hydroxybutyric acid (GHB) for alcohol withdrawal syndrome (AWS) in hospitalized patients with diagnosis of liver cirrhosis. An 11-year observational retrospective study on patients affected by liver cirrhosis and alcohol use disorder (AUD) was performed using data from the Medical Toxicology Unit of Careggi University Hospital in Florence (Italy). A multivariate logistic regression was performed to estimate the probability of having a CIWA-Ar Max 3-4 during hospitalization, an AWS length > 36 h, a hospitalization > 9 days, and the probability of developing drowsiness. A total of 166 AUD patients were included, of these 77 received GHB (70.13% within the first day of hospitalization) and 89 were treated without GHB. The majority were ≥ 40 years of age (87.35%) and males (80.12%). GHB patients were more likely to have a CIWA-Ar Max 3-4 during hospitalization (OR 3.76 [CI 95% 1.02-13.85]), and a longer hospitalization (OR 3.08 [95% CI 1.23-7.71]). Early GHB administration decreased the probability of CIWA-Ar Max worsening (OR 0.06 [95% CI 0.01-0.49]). GHB dose ≥ 100 mg/kg was not associated with the occurrence of drowsiness. Patients exposed to other sedative agents were more likely to experience drowsiness (OR 7.22 [95% CI 1.46-35.61]). The present real-world analysis underlines that GHB could be a valuable and safe option for the management of AWS in AUD patients affected by liver cirrhosis, also when administered early and even at higher than recommended dosages.

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.

Effects of cannabidiol, with and without ∆9-tetrahydrocannabinol, on anxiety-like behavior following alcohol withdrawal in mice.

Introduction: Alcohol use disorder (AUD) is commonly associated with anxiety disorders and enhanced stress-sensitivity; symptoms that can worsen during withdrawal to perpetuate continued alcohol use. Alcohol increases neuroimmune activity in the brain. Our recent evidence indicates that alcohol directly modulates neuroimmune function in the central amygdala (CeA), a key brain region regulating anxiety and alcohol intake, to alter neurotransmitter signaling. We hypothesized that cannabinoids, such as cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), which are thought to reduce neuroinflammation and anxiety, may have potential utility to alleviate alcohol withdrawal-induced stress-sensitivity and anxiety-like behaviors via modulation of CeA neuroimmune function. Methods: We tested the effects of CBD and CBD:THC (3:1 ratio) on anxiety-like behaviors and neuroimmune function in the CeA of mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure (CIE). We further examined the impact of CBD and CBD:THC on alcohol withdrawal behaviors in the presence of an additional stressor. Results: We found that CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-h withdrawal. At 24-h withdrawal, CBD alone reduced anxiety-like behaviors while CBD:THC had mixed effects, showing increased center time indicating reduced anxiety-like behaviors, but increased immobility time that may indicate increased anxiety-like behaviors. These mixed effects may be due to altered metabolism of CBD and THC during alcohol withdrawal. Immunohistochemical analysis showed decreased S100ß and Iba1 cell counts in the CeA at 4-h withdrawal, but not at 24-h withdrawal, with CBD and CBD:THC reversing alcohol withdrawal effects.. Discussion: These results suggest that the use of cannabinoids during alcohol withdrawal may lead to exacerbated anxiety depending on timing of use, which may be related to neuroimmune cell function in the CeA.

Evaluation of the Use of Phenobarbital and Benzodiazepines in the Management of Alcohol Withdrawal Syndrome in Patients Requiring Neurological/Neurosurgical Critical Care: A Propensity-Matched Analysis.

Objective There is growing interest in the use of phenobarbital for alcohol withdrawal syndrome in critically ill patients, though experience in neurologically injured patients is limited. The purpose of this study was to compare the safety and effectiveness of phenobarbital-containing alcohol withdrawal regimens versus benzodiazepine monotherapy in the neurocritical care unit. Methods We conducted a retrospective cohort study of adult patients admitted to the neurocritical care unit from January 2014 through November 2021 who received pharmacologic treatment for alcohol withdrawal. Treatment groups were defined as benzodiazepine monotherapy versus phenobarbital alone or in combination with benzodiazepines. The primary outcome was the percentage of patients requiring intubation after receiving alcohol withdrawal treatment. Secondary outcomes included all-cause, in-hospital mortality, intensive care unit length of stay, discharge disposition, change in Glasgow Coma Scale (GCS) score, and the use of adjunctive agents. Results We analyzed data from 156 patients, with 77 (49%) in the benzodiazepine group and 79 (51%) in the phenobarbital combination group. The groups were well-balanced for baseline characteristics, though more males (67, 85%) were in the phenobarbital group. Only three (1.9%) patients received phenobarbital monotherapy, and the rest (153, 98.1%) received combination therapy. The percentage of patients requiring mechanical ventilation was significantly higher in the phenobarbital combination group compared to benzodiazepine monotherapy (39% (n=31) versus 13% (n=10); OR: 4.33, 95% CI: 1.94-9.66; p<0.001). The use of adjunctive propofol and dexmedetomidine was higher in the phenobarbital group (propofol 35% (n= 28) versus 9% (n=7) and dexmedetomidine 30% (n=24) versus 5% (n=4), respectively). Patients in the phenobarbital group also had lower GCS scores and higher Clinical Institute Withdrawal Assessment of Alcohol (CIWA-Ar) scores during their intensive care unit admission, possibly suggesting more severe alcohol withdrawal. There was no difference in intensive care unit length of stay, all-cause, in-hospital mortality, discharge disposition, or therapeutic adjuncts. Conclusions Combination therapy of phenobarbital plus benzodiazepines was associated with higher odds of requiring mechanical ventilation. Few patients received phenobarbital monotherapy. Additional studies are needed to better compare the effects of phenobarbital monotherapy versus benzodiazepines in neurocritical patients.

Mental Manifestations and Biomarkers of Alcohol Consumption.

The purpose of this study is to examine healthcare usage, morbidities, and alcohol consumption monitoring in patients before a diagnosis of mental manifestations to assist in the early identification of individuals at risk. Biological markers of alcoholism are separated into two groups: those biological variables that highlight with great confidence and validate the presence of a predisposition to alcoholism, also called trait markers, or those that highlight alcohol consumption, called markers of alcoholism ("status markers"). Biomarkers are the true "gold standard" for the diagnosis of alcoholism. They are valuable for tracking evolution and progress during biological and psychological therapy and for highlighting relapse. This review compiles the existing data from research on healthcare utilization, comorbidities, and alcohol consumption monitoring in patients before a diagnosis of mental manifestations to aid in the early identification of individuals at risk. This documentary study took place over three to four months by searching for terms on the Science Direct platform, PubMed, Web of Science, and Google Scholar such as alcoholism, alcohol use disorders, alcohol abuse, and biomarkers. Studies reporting on the development, characteristics, and utilization of blood biomarkers for alcohol consumption were included in the search. The initial search included a number of 11.019 articles that contained the keywords biomarkers and alcohol. Finally, a total of 50 research articles were considered. I am involved in clinical studies, meta-analyses, reviews, and case studies regarding alcohol consumption detection, as well as potential alcohol markers.

When Consumption Leads to Catastrophe: A Case of Recurrent Alcohol Withdrawal Catatonia in an Adult Patient.

Catatonia is a motor dysregulation syndrome and a multifaceted neuropsychiatric behavioral syndrome distinguished by abnormal movements, immobility, abnormal behavior, and withdrawal, where patients are unable to move normally despite full physical capacity. Catatonia, in the background of alcohol withdrawal, is a fairly rare phenomenon. Therefore, we are reporting a case where the patient has a history of binge alcohol consumption, with catatonia reoccurring with his withdrawal symptoms, and no other illicit drug use in his history. Its rarity, complex presentation, and potential diagnostic pitfalls necessitate heightened awareness among healthcare professionals.

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.

Oral ethanol prescribing for alcohol withdrawal syndrome: initial findings and future directions following implementation within a United Kingdom National Health Service setting.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSIONS: 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.

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

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

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.

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.

Alterations in Neurotrophins in Alcohol-Addicted Patients during Alcohol 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.

Replacing the Clinical Institute Withdrawal Assessment-Alcohol revised with the modified Richmond Agitation and Sedation Scale for alcohol withdrawal to support management of alcohol withdrawal symptoms: potential impact on length of stay and complications.

PURPOSE: We evaluated impact on length of stay and possible complications of replacing the Clinical Institute Withdrawal Assessment-Alcohol Revised (CIWA-Ar) scale with a slightly modified Richmond Agitation and Sedation Scale (mRASS-AW) to support managing patients admitted with alcohol withdrawal symptoms in a community hospital. Since mRASS-AW is viewed as easier and quicker to use than CIWA-Ar, provided use of mRASS-AW does not worsen outcomes, it could be a safe alternative in a busy ED environment and offer an opportunity to release nursing time to care. METHODS: Retrospective time-series analysis of mean quarterly length of stay. All analyses exclusively used our hospital's administrative discharge diagnoses database. During April 1st 2012 to December 14th 2014, the CIWA-Ar was used in the ED and in-patient units to guide benzodiazepine dosing decisions for alcohol withdrawal symptoms. After this point, CIWA-Ar was replaced with mRASS-AW. Data was evaluated until December 31st 2020. PRIMARY OUTCOME: mean quarterly length of stay. SECONDARY OUTCOMES: delirium, intensive care unit (ICU) admission, other post-admission complications, mortality. RESULTS: N = 1073 patients. No association between length of stay and scale switch (slope change 0.3 (95% CI - 0.03 to 0.6), intercept change, 0.06 (- 0.03 to 0.2). CIWA-Ar (n = 317) mean quarterly length of stay, 5.7 days (95% 4.2-7.1), mRASS-AW (n = 756) 5.0 days (95% CI 4.3-5.6). Incidence of delirium, ICU admission or mortality was not different. However, incidence of other post-admission complications was higher with CIWA-Ar (6.6%) than mRASS-AW (3.4%) (p = 0.020). CONCLUSIONS: This was the first study to compare patient outcomes associated with using mRASS-AW for alcohol withdrawal symptoms outside the ICU. Replacing CIWA-Ar with mRASS-AW did not worsen length of stay or complications. These findings provide some evidence that mRASS-AW could be considered an alternative to CIWA-Ar and potentially may provide an opportunity to release nursing time to care.

ABSTRAIT: BUT: Nous avons évalué l'impact sur la durée du séjour et les complications possibles du remplacement de l'échelle Clinical Institute Withdrawal Assessment- Alcohol Revised (CIWA-Ar) par une échelle d'agitation et de sédation de Richmond légèrement modifiée (mRASS-AW) soutenir la prise en charge des patients admis avec des symptômes de sevrage d'alcool dans un hôpital communautaire. Étant donné que le mRASS-AW est considéré comme plus facile et plus rapide à utiliser que le CIWA-Ar, à condition que l'utilisation du mRASS-AW n'aggrave pas les résultats, il pourrait s'agir d'une solution de rechange sécuritaire dans un environnement de SU occupé et offrir une occasion de libérer du temps pour les soins infirmiers. MéTHODES: Analyse rétrospective de séries chronologiques de la durée moyenne trimestrielle du séjour. Toutes les analyses utilisaient exclusivement la base de données des diagnostics de sortie administrative de notre hôpital. Entre le 1er avril 2012 et le 14 décembre 2014, le CIWA-Ar a été utilisé dans les unités de soins intensifs et de soins aux patients hospitalisés pour guider les décisions de dosage des benzodiazépines pour les symptômes de sevrage de l'alcool. Après ce point, CIWA-Ar a été remplacé par mRASS-AW. Les données ont été évaluées jusqu'au 31 décembre 2020. Résultat principal : durée moyenne trimestrielle du séjour. Résultats secondaires : délire, admission en unité de soins intensifs (USI), autres complications post-admission, mortalité. RéSULTATS: N = 1073 patients. Aucune association entre la durée de séjour et le changement d'échelle (changement de pente 0,3 (IC à 95 % -0,03 à 0,6), changement d'interception, 0,06 (-0,03 à 0,2). CIWA-Ar (n = 317) durée moyenne trimestrielle du séjour, 5,7 jours (95 % 4,2 à 7,1), mRASS-AW (n = 756) 5,0 jours (95 % IC 4,3 à 5,6). L'incidence du délire, de l'admission aux soins intensifs ou de la mortalité n'était pas différente. Cependant, l'incidence d'autres complications post-admission était plus élevée avec CIWA-Ar (6,6%) que mRASS-AW (3,4%) (p = 0,020). CONCLUSIONS: Il s'agissait de la première étude à comparer les résultats des patients associés à l'utilisation du mRASS-AW pour les symptômes de sevrage alcoolique en dehors des soins intensifs. Le remplacement de CIWA-Ar par mRASS-AW n'a pas aggravé la durée du séjour ou les complications. Ces résultats fournissent certaines preuves que le mRASS-AW pourrait être considéré comme une alternative au CIWA-Ar et pourrait potentiellement fournir une occasion de libérer du temps de soins infirmiers.

Protein kinase C epsilon-mediated modulation of T-type calcium channels underlies alcohol withdrawal hyperexcitability in the midline thalamus.

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.