Delirium tremens (DT) is the most severe and life-threatening manifestation of alcohol withdrawal. Prompt identification and treatment are crucial in the clinical management of DT, but laboratory markers in this context are still lacking. Neurofilament light chain (NfL) has been proposed as a novel blood marker of neuroaxonal pathology. Therefore, we investigated the association between plasma NfL levels on admission and the occurrence of DT in patients with alcohol use disorder (AUD). NfL levels were measured on admission in 224 patients with AUD undergoing alcohol withdrawal treatment and in 116 healthy individuals. We monitored patients with AUD during the following 2 weeks of hospitalization and categorized them according to the prospective occurrence of DT (n = 25) or not (n = 199). Plasma NfL levels at admission were highest in patients who later developed DT, compared to AUD patients without DT, and healthy individuals (63.1 ± 47.2, 24.0 ± 22.4, 11.8 ± 6.1 pg/mL, respectively, p < 0.001). Receiver operating characteristic analysis revealed that a cut-off NfL level of 27.2 pg/mL could discriminate AUD patients who later developed DT (sensitivity: 80.0 %; specificity: 72.4 %; area under the curve: 0.84, p < 0.001), with an odds ratio of 9.43 (95 % CI 3.26-27.32; p < 0.001) for the risk of developing DT. Our findings suggest that NfL levels at admission may predict DT occurrence in patients with AUD and implicate neuroaxonal pathology in the pathophysiology of DT. Further research is needed to validate these findings and to explore the underlying neurobiological mechanisms.

Background Alcohol withdrawal severity is widely assessed and objectified using the Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) scale. However, the subjective nature of this scale has led to several studies that scrutinized the relationship of various blood parameters to assess withdrawal severity. The aim of this study was to analyze the relationship of various laboratory biomarkers with the severity of alcohol withdrawal. Methods This was a retrospective study of 200 cases admitted to Rashid Hospital, UAE, with the diagnosis of alcohol withdrawal syndrome. Severity was assessed using CIWA-Ar. The average CIWA-Ar score was calculated and analyzed against creatine phosphokinase (CPK) on admission days one, two, and three using a correlation coefficient. Sixteen other blood markers were also analyzed, including hemoglobin, mean corpuscular volume, white blood cell (WBC), platelets, alanine transaminase, aspartate aminotransferase, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, gamma-glutamyl transferase, albumin, international normalized ratio, lactate dehydrogenase, sodium, potassium, magnesium, phosphate, and creatinine. Additionally, the duration of alcohol intake and the timing of the last alcohol intake were also examined in relation to the severity of alcohol withdrawal. Results Average CIWA-Ar exhibited a positive relationship with CPK on admission day one (r=0.2 (p=0.008)); day two (r= 0.25 (p=0.003)), and day three (r=0.42 (p<0.001)). WBC and AST showed a relatively rising trend with higher CIWA scores (average values, however, remain within the normal range). The results were not statistically significant (p>0.01). Serum potassium and magnesium levels followed a decreasing trend with rising CIWA (average values, however, remained within the normal range). These results were also not found to be statistically significant (p>0.1). Conclusion A high CPK level was associated with the severity of alcohol withdrawal syndrome (SAWS). Low serum potassium and magnesium and high WBC and AST can be associated with alcohol withdrawal severity. These routine laboratory tests can serve as objective indicators of severity in addition to using the CIWA-Ar score for AWS, enabling prompt management and prevention of complications.

We conducted a review of all studies comparing clinical aspects of alcohol withdrawal syndrome (AWS) between men and women.

Five databases (PubMed, Cochrane, EMBASE, Scopus and Clinical Trials) were searched for clinical studies using the keywords "alcohol withdrawal syndrome" or "delirium tremens" limited to "sex" or "gender" or "sex difference" or "gender difference." The search was conducted on May 19, 2023. Two reviewers selected studies including both male and female patients with AWS, and they compared males and females in type of AWS symptoms, clinical course, complications, and treatment outcome.

Thirty-five observational studies were included with a total of 318,730 participants of which 75,346 had AWS. In twenty of the studies, the number of patients presenting with or developing AWS was separated by sex, resulting in a total of 8,159 (12.5%) female patients and a total of 56,928 (87.5%) male patients. Despite inconsistent results, males were more likely than females to develop complicated AWS [delirium tremens (DT) and AW seizures, collective DT in Males vs. females: 1,792 (85.4%) vs. 307 (14.6%), and collective seizures in males vs. females: 294 (78%) vs. 82 (22%)]. The rates of ICU admissions and hospital length of stay did not show sex differences. Although variable across studies, compared to females, males received benzodiazepine treatment at higher frequency and dose. One study reported that the time from first hospitalization for AWS to death was approximately 1.5 years shorter for males and males had higher mortality rate [19.5% (197/1,016)] compared to females [16% (26/163)].

Despite the significant heterogeneity of the studies selected and the lack of a focus on investigating potential sex differences, this review of clinical studies on AWS suggests that men and women exhibit different AWS manifestations. Large-scale studies focusing specifically on investigating sex difference in AWS are needed.

Delirium Tremens (DT) is a severe form of alcohol withdrawal that can be fatal if not recognized early and treated appropriately. In our study, we aimed to determine the role of Neutrophil-Lymphocyte ratio (NLR), a marker of systemic inflammation, in predicting the development of DT. This retrospective study was conducted in an alcohol and drug treatment center between March 2017 and March 2020. A total of 212 patients with a diagnosis of alcohol use disorder who were admitted to a special care unit after alcohol withdrawal were included. Blood tests were collected within 24 hours of the patients' admission. Comparisons were made according to whether the patients developed DT during the hospitalization. DT was diagnosed in 24.1% of the patients. It was determined that higher NLR level (odds ratio [OR]: 4.38, 95%CI: 2.58-7.43) and history of DT (OR: 1.33, 95%CI: 1.23-11.73) are independent risk factors for the development of DT in the logistic regression analysis. The optimal cut-off value of NLR in predicting DT was 2.67 (sensitivity: 82.4%, specificity: 88.8%). The ROC curve of NLR showed a larger area under the curve (AUC) than the curves of other systemic inflammation markers. NLR is a simple, practical and inexpensive marker that can predict the development of DT in patients with alcohol withdrawal syndrome.

Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T0-T4 continuum to advance the care of hospitalized patients who experience SAWS. Methods: Clinicians and researchers with unique and complementary expertise in basic, clinical, and implementation research related to unhealthy alcohol consumption and alcohol withdrawal were invited to participate in a workshop at the American Thoracic Society 2019 International Conference. The committee was subdivided into four groups on the basis of interest and expertise: T0-T1 (basic science research with translation to humans), T2 (research translating to patients), T3 (research translating to clinical practice), and T4 (research translating to communities). A medical librarian conducted a pragmatic literature search to facilitate this work, and committee members reviewed and supplemented the resulting evidence, identifying key knowledge gaps. Results: The committee identified several investigative opportunities to advance the care of patients with SAWS in each domain of the translational science spectrum. Major themes included 1) the need to investigate non-γ-aminobutyric acid pathways for alcohol withdrawal syndrome treatment; 2) harnessing retrospective and electronic health record data to identify risk factors and create objective severity scoring systems, particularly for acutely ill patients with SAWS; 3) the need for more robust comparative-effectiveness data to identify optimal SAWS treatment strategies; and 4) recommendations to accelerate implementation of effective treatments into practice. Conclusions: The dearth of evidence supporting management decisions for hospitalized patients with SAWS, many of whom require critical care, represents both a call to action and an opportunity for the American Thoracic Society and larger scientific communities to improve care for a vulnerable patient population. This report highlights basic, clinical, and implementation research that diverse experts agree will have the greatest impact on improving care for hospitalized patients with SAWS.

Alcohol abuse is a major problem worldwide and it affects people's health and economy. There is a relapse in alcohol intake due to alcohol withdrawal. Alcohol withdrawal anxiety-like behavior is a symptom that appears 6-24 h after the last alcohol ingestion.

The present study was designed to explore the protective effect of a standardized polyherbal preparation POL-6 in ethanol withdrawal anxiety in Wistar rats. POL-6 was prepared by mixing the dried extracts of six plants Bacopa monnieri, Hypericum perforatum, Centella asiatica, Withania somnifera, Camellia sinesis, and Ocimum sanctum in the proportion 2:1:2:2:1:2 respectively. POL-6 was subjected to phytochemical profiling through LC-MS, HPLC, and HPTLC. The effect of POL-6 on alcohol withdrawal anxiety was tested using a two-bottle choice drinking paradigm model giving animals' free choice between alcohol and water for 15 days. Alcohol was withdrawn on the 16th day and POL-6 (20, 50, and 100 mg/kg, oral), diazepam (2 mg/kg) treatment was given on the withdrawal days. Behavioral parameters were tested using EPM and LDT. On the 18th day blood was collected from the retro-orbital sinus of the rats and alcohol markers ALT, AST, ALP, and GGT were studied. At end of the study, animals were sacrificed and the brain was isolated for exploring the influences of POL-6 on the mRNA expression of GABAA receptor subunits in the amygdala and hippocampus.

Phytochemical profiling showed that POL-6 contains major phytoconstituents like withaferin A, quercetin, catechin, rutin, caeffic acid, and β-sitosterol. In-vivo studies showed that POL-6 possesses an antianxiety effect in alcohol withdrawal. Gene expression studies on the isolated brain tissues showed that POL-6 normalizes the GABAergic transmission in the amygdala and hippocampus of the rats.

The study concludes that POL-6 may have therapeutic potential for treating ethanol-type dependence.

Inpatient alcohol withdrawal syndrome (AWS) is common and early treatment improves outcomes, but no prior study has used electronic health record (EHR) data, available at admission, to predict the probability of inpatient AWS. This study estimated the probability of inpatient AWS using prior-year EHR data, hypothesizing that documented alcohol use disorder (AUD) and AWS would be strongly associated with inpatient AWS while exploring associations with other patient characteristics.

The study investigated patients hospitalized ≥24 hours on medical services in the Veterans Health Administration during 2013 using EHR data extracted from the Veterans Health Administration Corporate Data Warehouse. ICD-9-CM diagnosis code, demographic, and healthcare utilization data documented in the year before admission defined prior-year AUD, AWS, and other factors associated with inpatient AWS. The primary outcome, inpatient AWS, was defined by inpatient ICD-9-CM codes.

The unadjusted probability of AWS was 5.0% (95% CI 4.5%-5.4%) among 209,151 medical inpatients overall, 26.4% (95% CI 24.4%-28.4%) among those with prior-year AUD, and 62.5% (95% CI 35.2%-39.7%) among those with prior-year AWS. Of those with AWS, 86% had documented prior-year AUD and/or AWS. Other patient characteristics associated with increased probability of inpatient AWS (P < 0.001) were: male sex, single relationship status, homelessness, seizure, and cirrhosis.

Although inpatient providers often use history to predict AWS, this is the first study in hospitalized patients to inform and validate this practice, showing that prior-year diagnosis of AUD and/or AWS in particular, can identify the majority of inpatients who should be monitored for AWS.

Alcohol withdrawal and its consequences are a common concern for the large numbers of patients who present to emergency departments (EDs) with alcohol use disorders. While the majority of patients who go on to develop alcohol withdrawal experience only mild symptoms, a small proportion will experience seizures or delirium tremens. The aim of this study was to develop a tool to predict the need for hospital admission in patients at risk for alcohol withdrawal using only objective criteria that are typically available during the course of an ED visit.

We conducted a retrospective study at an academic medical center. Our primary outcome was severe alcohol withdrawal syndrome (SAWS), which we defined as a composite of delirium tremens, seizure, or use of high benzodiazepine doses. All candidate predictors were abstracted from the electronic health record. A logistic regression model was constructed using the derivation dataset to create the alcohol withdrawal triage tool (AWTT).

Of the 2038 study patients, 408 20.0 %) developed SAWS. We identified eight independent predictors of SAWS. Each of the predictors in the regression model was assigned one point. Summing the points for each predictor generated the AWTT score. An AWTT score of 3 or greater was defined as high risk based on sensitivity of 90 % and specificity of 47 % for predicting SAWS.

We were able to identify a set of objective, timely, independent predictors of SAWS. The predictors were used to create a novel clinical prediction rule, the AWTT.

Benzodiazepines (BDZs) have been the treatment of choice for alcohol withdrawal syndrome (AWS); however, they are associated with several side effects and also have abuse potential. In some studies, the use of baclofen has been effective in reducing symptoms of alcohol withdrawal symptoms.

The objective of this study was to compare the efficacy of baclofen and benzodiazepine (lorazepam) in reducing symptoms of AWS.

It was a single-center, randomized, open-label study. Patients with alcohol dependence syndrome were enrolled in the study and randomized into two groups using computer-generated random table number. Baclofen (experimental group, 10 mg three times a day) and BZDs (control group, lorazepam, 8-12 mg/day in divided doses) were orally administered for reducing symptoms of alcohol withdrawal. Both groups received Vitamin B1 (100 mg/day through intramuscular route) and psychotherapeutic interventions. The severity of alcohol dependence was assessed by using the Severity of Alcohol Dependence Questionnaire, and alcohol withdrawal was assessed with the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar).

Sixty-six patients were randomized (baclofen n = 34, benzodiazepine (BZD) group n = 32). Two patients (one patient in each group) had complicated withdrawal symptoms and were dropped from the final analysis. There was a significant reduction in alcohol withdrawal symptoms in both groups. There were no significant differences in CIWA-Ar scores between the two groups. Both the drugs were well-tolerated.

Baclofen and lorazepam are comparable in efficacy and tolerability in reducing symptoms of AWS.

Although severe alcohol withdrawal syndrome (SAWS) is associated with substantial morbidity and mortality, most at-risk patients will not develop this syndrome. Predicting its occurrence is important because the mortality rate is high when untreated.

To assess the accuracy and predictive value of symptoms and signs for identifying hospitalized patients at risk of SAWS, defined as delirium tremens, withdrawal seizure, or clinically diagnosed severe withdrawal.

MEDLINE and EMBASE (1946-January 2018) were searched for articles investigating symptoms and signs predictive of SAWS in adults. Reference lists of retrieved articles were also searched.

Original studies that were included compared symptoms, signs, and risk assessment tools among patients who developed SAWS and patients who did not.

Data were extracted and used to calculate likelihood ratios (LRs), sensitivity, and specificity. A meta-analysis was performed to calculate summary LR.

Of 530 identified studies, 14 high-quality studies that included 71 295 patients and 1355 relevant cases of SAWS (1051 cases), seizure (53 cases), or delirium tremens (251 cases) were analyzed. A history of delirium tremens (LR, 2.9 [95% CI 1.7-5.2]) and baseline systolic blood pressure 140 mm Hg or higher (LR, 1.7 [95% CI, 1.3-2.3) were associated with an increased likelihood of SAWS. No single symptom or sign was associated with exclusion of SAWS. Six high-quality studies evaluated combinations of clinical findings and were useful for identifying patients in acute care facilities at high risk of developing SAWS. Of these combinations, the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) was most useful, with an LR of 174 (95% CI, 43-696; specificity, 0.93) when patients had 4 or more individual findings and an LR of 0.07 (95% CI, 0.02-0.26; sensitivity, 0.99) when there were 3 or fewer findings.

Assessment tools that use a combination of symptoms and signs are useful for identifying patients at risk of developing severe alcohol withdrawal syndrome. Most studies of these tools were not fully validated, limiting their generalizability.

Baclofen shows potential for rapidly reducing symptoms of severe alcohol withdrawal syndrome (AWS) in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review published in 2015, Issue 4.

To assess the efficacy and safety of baclofen for people with AWS.

We updated our searches of the following databases to March 2017: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language.

We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies.

We used standard methodological procedures expected by Cochrane.

We included three RCTs with 141 randomised participants. We did not perform meta-analyses due to the different control interventions. For the comparison of baclofen and placebo (1 study, 31 participants), there was no significant difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores (very low quality evidence). For the comparison of baclofen and diazepam (1 study, 37 participants), there was no significant difference in CIWA-Ar scores (very low quality evidence), adverse events (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence). For the comparison of baclofen and chlordiazepoxide (1 study, 60 participants), there was no significant difference in CIWA-Ar scores (mean difference (MD) 1.00, 95% CI 0.70 to 1.30; very low quality evidence), global improvement (MD 0.10, 95% CI -0.03 to 0.23; very low quality evidence), adverse events (RD 2.50, 95% CI 0.88 to 7.10; very low quality of evidence), dropouts (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence).

No conclusions can be drawn about the efficacy and safety of baclofen for the management of alcohol withdrawal because we found insufficient and very low quality evidence.

Alcohol withdrawal delirium (AWD) or delirium tremens (DT) is associated with severe complications and high mortality. Prospectively identifying patients with increased risk of developing DT would have important preventive and therapeutic implications. Thus, the present study aimed to identify clinical risk factors predicting the development of DT.

The study was a cross-sectional quasi-experimental one with equivalent control group, conducted at a tertiary hospital from August 2014 to May 2015. Forty adult male inpatients, diagnosed with DT, were compared with forty age- and sex-matched inpatients in alcohol withdrawal state without delirium. Assessments were done using confusion assessment method, Clinical Institute Withdrawal Assessment of Alcohol Scale, and Mini-Mental Status Examination. For group comparisons, Pearson's Chi-square test and independent sample t-test were used; logistic regression was applied to identify predictors followed by receiver operating characteristic curve analysis.

Heavy drinking (P = 0.005; odds ratio [OR]: 1.17, confidence interval [CI]: 1.05-1.31), continuous pattern of drinking (P = 0.027; OR: 4.67, CI: 1.19-18.33), past history of delirium (P = 0.009; OR: 552.8, CI: 4.88-625.7), alcohol-induced psychosis (P = 0.002; OR: 74.6, CI: 4.68-1190), and presence of cognitive deficits (P = 0.044; OR: 12.5, CI: 1.07-147.3) emerged as strong predictors of AWD.

The risk factors found can be easily evaluated in a clinical setting for physicians to readily identify patients at risk for developing DT and plan intensive therapies for them. At a neurobiological level, patients with preexisting brain neurotransmitter disturbances are at greater risk for developing DT.

Severe alcoholic hepatitis is implicated as a costly, worldwide public health issue with high morbidity and mortality. The one-month survival for severe alcoholic hepatitis is low with mortality rates high as 30%-50%. Abstinence from alcohol is the recommended first-line treatment. Although corticosteroids remain as the current evidence based option for selected patients with discriminant function > 32, improvement of short-term survival rate may be the only benefit. Identification of individuals with risk factors for the development of severe alcoholic hepatitis may provide insight to the diverse clinical spectrum and prognosis of the disease. The understanding of the complex pathophysiologic processes of alcoholic hepatitis is the key to elucidating new therapeutic treatments. Newer research describes the use of gut microbiota modification, immune modulation, stimulation of liver regeneration, caspase inhibitors, farnesoid X receptors, and the extracorporeal liver assist device to aid in hepatocellular recovery. Liver transplantation can be considered as the last medical option for patients failing conventional medical interventions. Although the preliminary data is promising in patients with low risk of recividism, controversy remains due to organ scarcity. This review article comprehensively summarizes the epidemiology, pathophysiology, risk factors, and prognostic indicators of severe alcoholic hepatitis with a focus on the current and emerging therapeutics.

Unhealthy alcohol use is common and routine screening is essential to identify patients and initiate appropriate treatment. At-risk or hazardous drinking is best managed with brief interventions, which can be performed by any provider and are designed to enhance patients' motivations and promote behavioral change. Alcohol withdrawal can be managed, preferably with benzodiazepines, using a symptom-triggered approach. Twelve-step programs and provider-driven behavioral therapies have robust data supporting their effectiveness and patients with alcohol use disorder should be referred for these services. Research now support the use of several FDA-approved medications that aid in promoting abstinence and reducing heavy drinking.

The treatment baclofen shows potential for rapidly reducing symptoms of severe alcohol withdrawal syndrome (AWS) in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane review published in Issue 2, 2013.

To assess the efficacy and safety of baclofen for people with AWS.

We searched the Cochrane Drugs and Alcohol Group Specialised Register (searched 13 January 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 1), MEDLINE (1966 to January 2015), EMBASE (1980 to January 2015), and CINAHL (1982 to January 2015). We also searched registers of ongoing trials, including ClinicalTrials.gov, the ISRCTN registry, and the European Clinical Trials Database. At the same time, we handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language.

We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies.

Two review authors independently assessed references retrieved for possible inclusion. Any disagreements were resolved by an independent party. We contacted study authors for additional information where needed. We collected adverse effects information from the trials.

Two RCTs with a total of 81 participants were eligible according to the inclusion criteria. One study suggested that both baclofen and diazepam significantly decreased the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) score, without any significant difference between the two interventions. The other study showed no significant difference in CIWA-Ar score between baclofen and placebo, but a significantly decreased dependence on high-dose benzodiazepines with baclofen compared to placebo. Only one study reported on the safety of baclofen, without any side effects.

The evidence for recommending baclofen for AWS is insufficient. We therefore need more well-designed RCTs to prove its efficacy and safety.

To date, no screening tools for alcohol withdrawal syndromes (AWS) have been validated in the medically ill. Although several tools quantify the severity of AWS (e.g., Clinical Institute Withdrawal Assessment for Alcohol [CIWA]), none identify subjects at risk of AWS, thus missing the opportunity for timely prophylaxis. Moreover, there are no validated tools for the prediction of complicated (i.e., moderate to severe) AWS in the medically ill.

Our goals were (1) to conduct a systematic review of the published literature on AWS to identify clinical factors associated with the development of AWS, (2) to use the identified factors to develop a tool for the prediction of alcohol withdrawal among patients at risk, and (3) to conduct a pilot study to assess the validity of the tool.

For the creation of the Prediction of Alcohol Withdrawal Severity Scale (PAWSS), we conducted a systematic literature search using PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines for clinical factors associated with the development of AWS, using PubMed, PsychInfo, MEDLINE, and Cochrane Databases. Eligibility criteria included: (i) manuscripts dealing with human subjects, age 18 years or older, (ii) manuscripts directly addressing descriptions of AWS or its predisposing factors, including case reports, naturalistic case descriptions, and all types of clinical trials (e.g., randomized, single-blind, or open label studies), (iii) manuscripts describing characteristics of alcohol use disorder (AUD), and (iv) manuscripts dealing with animal data (which were considered only if they directly dealt with variables described in humans). Obtained data were used to develop the Prediction of Alcohol Withdrawal Severity Scale, in order to assist in the identification of patients at risk for complicated AWS. A pilot study was conducted to assess the new tool's psychometric qualities on patients admitted to a general inpatient medicine unit over a 2-week period, who agreed to participate in the study. Blind to PAWSS results, a separate group of researchers retrospectively examined the medical records for evidence of AWS.

The search produced 2802 articles describing factors potentially associated with increased risk for AWS, increased severity of withdrawal symptoms, and potential characteristics differentiating subjects with various forms of AWS. Of these, 446 articles met inclusion criteria and underwent further scrutiny, yielding a total of 233 unique articles describing factors predictive of AWS. A total of 10 items were identified as correlated with complicated AWS (i.e., withdrawal hallucinosis, withdrawal-related seizures, and delirium tremens) and used to construct the PAWSS. During the pilot study, a total of 68 subjects underwent evaluation with PAWSS. In this pilot sample the sensitivity, specificity, and positive and negative predictive values of PAWSS were 100%, using the threshold score of 4.

The results of the literature search identified 10 items which may be correlated with risk for complicated AWS. These items were assembled into a tool to assist in the identification of patients at risk: PAWSS. The results of this pilot study suggest that PAWSS may be useful in identifying risk of complicated AWS in medically ill, hospitalized individuals. PAWSS is the first validated tool for the prediction of severe AWS in the medically ill and its use may aid in the early identification of patients at risk for complicated AWS, allowing for prophylaxis against AWS before severe alcohol withdrawal syndromes develop.

Delirium tremens represents the most severe complication of alcohol withdrawal syndrome and, in its complications, significantly increases the morbidity and mortality of patients. Alcohol withdrawal delirium is characterized by features of alcohol withdrawal itself (tremor, sweating, hypertension, tachycardia etc.) together with general delirious symptoms such as clouded consciousness, disorientation, disturbed circadian rhythms, thought processe and sensory disturbances, all of them fluctuating in time. The treatment combines a supportive and symptomatic approach. Benzodiazepines in supramaximal doses are usually used as drugs of choice but in some countries such as the Czech Republic or Germany, clomethiazole is frequently used as well.

A computer search of the all the literature published between 1966 and December 2012 was accomplished on MEDLINE and Web of Science with the key words "delirium tremens", "alcohol withdrawal", "treatment" and "pharmacotherapy". There were no language or time limits applied.

When not early recognized and treated adequately, delirium tremens may result in death due to malignant arrhythmia, respiratory arrest, sepsis, severe electrolyte disturbance or prolonged seizures and subsequent trauma. Owing to these possible fatalities and other severe unexpected complications, delirium tremens should be managed at an ICU or wards ensuring vital signs monitoring. In symptomatic treatment, high doses of benzodiazepines, especially lorazepam, diazepam and oxazepam are considered the gold standard drugs. Supportive therapy is also of great importance.

The treatment baclofen can rapidly reduce symptoms of severe alcohol withdrawal syndrome (AWS) in alcoholic patients, with a significant reduction in the cost. Baclofen is easy to manage, and rare euphoria, craving and other pleasant effects are reported by patients treated with baclofen.

To assess the efficacy and safety of baclofen for patients with AWS.

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (October 2012), MEDLINE (1966 to October 2012), EMBASE (1980 to October 2012) and CINAHL (1982 to October 2012). We also searched registers of ongoing trials, for example ClinicalTrials.gov, Controlled-trials.com, EUDRACT, etc. At the same time, we handsearched the references quoted in the identified trials, and contacted researchers, pharmaceutical companies and relevant trial authors seeking information about unpublished or uncompleted trials. All searches included the non-English language literature.

All randomized controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for patients with AWS. Uncontrolled, non-randomized or quasi-randomized trials were excluded. Both parallel group and cross-over design were included.

Two review authors independently assessed references retrieved for possible inclusion. All disagreements were resolved by an independent party. Study authors were contacted for additional information. Adverse effects information was collected from the trials.

We identified a total of 113 references from all electronic databases searched excluding duplicates. After screening of titles and abstracts, full papers of 10 studies were obtained and assessed for eligibility. Finally, two RCTs with 81 participants were eligible according to the inclusion criteria. Regarding the efficacy, one study suggested that both baclofen and diazepam significantly decreased the Clinical Institute Withdrawal Assessment of Alcohol Scale Revised (CIWA-Ar) score, without any significant difference between the two interventions. The other study showed no significant difference in CIWA-Ar score between baclofen and placebo but a significantly decreased dependence on high-dose benzodiazepines with baclofen compared to placebo. Meanwhile, only one study reported the safety outcomes and there were no side effects in either the baclofen or diazepam groups.

The evidence for recommending baclofen for AWS is insufficient. More well designed RCTs are needed to prove its efficacy and safety.

Animal studies suggest that in alcohol withdrawal the balance of neurotransmitters gamma aminobutyric acid (GABA) and glutamate is altered. To test this in humans, we aimed to measure plasma levels of glutamate, GABA and glutamate/GABA ratio in alcoholic patients presenting with complicated AWS with the same values in non-alcohol abuser/dependent controls and to determine prognostic factors for severe withdrawal.

88 patients admitted to the emergency room for acute alcohol intoxication (DSM-IV) were prospectively included. Measurements of GABA and glutamate were performed on admission (Time 1, T1) and after 12 ± 2 h (T2). The experimental group (EG) was composed of 23 patients who presented at T2 with a severe AWS. The control group (CG) consisted of healthy subjects paired with the EG (gender and age). Logistic regression was performed in order to compare associated clinical and biological variables that could predict severe withdrawal.

The concentration of GABA in the EG at T1 was significantly lower than that in the CG. The concentration of glutamate in the EG at T1 was significantly higher than that in the CG. The glutamate/GABA ratio in the EG at T1 was significantly higher than the ratio in the CG. With a multivariate logistic regression model, glutamate level at admission remained the only criterion identified as a predictor of AWS at 12 h.

Decreased synthesis of GABA and increased synthesis of glutamate might be related to withdrawal symptoms experienced on brutal cessation of chronic alcohol intake.

The treatment of baclofen can rapidly reduce symptoms of severe alcohol withdrawal syndrome (AWS) in alcoholic patients, with a significant reduction in the cost. Baclofen is easily manageable, what's more, no patient treated with baclofen reported euphoria or other pleasant effects caused by the drug and no subject reported any degree of craving for the drug.

To assess the efficacy and safety of baclofen for patients with alcohol withdrawal syndrome.

We searched the Cochrane Central Register of Controlled Trials (September 2010), MEDLINE (1966 to September 2010), EMBASE (1980 to September 2010), and CINAHL (1982 to September 2010). We also searched the following registers of ongoing trials, e.g. Clinicaltrials.gov, Controlled trials.com, EUDRACT, etc. At the same time, we handsearched the references quoted in the identified trials, contact researchers, pharmaceutical companies and relevant trial authors seeking information about unpublished or incomplete trials. All searches included non-English language literature.

All randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for patients with AWS. Uncontrolled, non-randomised or quasi-randomised trials were excluded. Both parallel group and cross-over design were included.

Two reviewers independently assessed references retrieved for possible inclusion. All disagreements were resolved by an independent party. Study authors were contacted for additional information. Adverse effects information was collected from the trials.

We identified a total of 82 references from all electronic databases searched excluding duplicate. After screening of titles and abstracts, full papers of 7 studies were obtained and assessed for eligibility. Finally, only one study met the inclusion criteria, with 37 participants.

The evidence of recommending baclofen for AWS is insufficient. More well designed RCTs are demanded to further prove its efficacy and safety.

Brain-derived neurotrophic factor (BDNF) is associated with alcohol addiction and withdrawal-related neurotoxicity. Delirium tremens (DT) is the most serious complication of alcohol withdrawal syndrome (AWS). In this study, we explored the differences in serum BDNF levels, measured at baseline and 1 week after alcohol withdrawal among alcoholic patients with and without DT.

Sixty-five inpatients, fulfilling the DSM-IV criteria of alcohol dependence and admitted for alcohol detoxification, as well as 39 healthy control subjects were enrolled. The alcoholic patients were divided by the appearance of DTs into the DT group (n = 25) and non-DT group (n = 40). We collected blood samples of the patient groups on the first and seventh days of alcohol withdrawal and measured serum BDNF levels by sandwich enzyme-linked immunosorbent assay.

Serum BDNF levels differed significantly among the three groups: (i) control group 14.8 ± 4.7 ng/ml; (ii) non-DT group 12.3 ± 3.3 ng/ml; (iii) DT group 6.2 ± 2.6 ng/ml (p < 0.001). One week after alcohol withdrawal, the BDNF levels increased significantly for both alcoholic groups. While non-DT group had comparable BDNF levels (13.4 ± 3.5 ng/ml) with controls, the DT group still exhibited lower levels (8.9 ± 4.4 ng/ml).

This study suggests chronic drinking leads to a reduction in BDNF levels, and patients with more deficient BDNF expression are vulnerable to the development of DTs. Additionally, BDNF levels elevated after prompt alcohol detoxification treatment. These findings indicate that BDNF could involve modifying the phenotypes of AWS as well as the pertinent neuroadaptive processes of alcohol dependence.

The aim of this trial was to compare lorazepam with non-benzodiazepine medications such as pregabalin and tiapride in the treatment of alcohol withdrawal syndrome (AWS). These drugs were chosen for their inhibitorial effects on the hypersecretion of neurotransmitters usually observed in AWS. Craving reduction and improvement of psychiatric symptoms were the secondary end-points.

One hundred and ninety subjects affected by current alcohol dependence were considered consecutively: 111 were enrolled and divided into three groups of 37 subjects each. Within a treatment duration of 14 days, medication was given up to the following maximum doses (pregabalin 450 mg/day; tiapride 800 mg/day; lorazepam 10 mg/day). Withdrawal (CIWA-Ar), craving [visual analogue scale (VAS); Obsessive and Compulsive Drinking Scale (OCDS)], psychiatric symptoms [Symptom Check List 90 Revised (SCL-90-R)] and quality of life (QL-index) rating scales were applied.

On the CIWA-Ar score, all the groups showed a significant reduction between times (P < 0.001) with a higher reduction for the pregabalin group (P < 0.01) on items regarding headache and orientation. Retention in treatment was lower in the tiapride group (P < 0.05), while the number of subjects remaining alcohol free was higher in the pregabalin group (P < 0.05). Significant reduction between baseline and the end of the treatment was found in all the groups at the OCDS and the VAS for craving, at the SCL-90-R and QL-index (P < 0.001).

All the medications in the trial showed evidence of safety and efficacy in the treatment of uncomplicated forms of AWS, with some particular differences. The efficacy of pregabalin was superior to that of tiapride, used largely in research trials and, for some measures, to that of the 'gold standard', lorazepam. Accordingly, pregabalin may be considered as a potentially useful new drug for treatment of AWS, deserving further investigation.

The clinical expressions of alcohol withdrawal syndrome (AWS) may vary and the factors determining these variations are not well-known. It would be useful to have a set of clinical tools capable of predicting which patients are likely to develop the more severe forms of the syndrome.

To analyse the clinical variables associated with the development of delirium tremens (DTs) in patients who were admitted to a general hospital with AWS.

Cohort study of AWS patients admitted to the Xeral Hospital in Lugo, Spain, between 1987 and 2003. The characteristics of patients with the syndrome who did not develop delirium tremens were contrasted with those who did. Cases presenting with DTs at diagnosis were excluded. The different clinical, epidemiological and biochemical variables reflective of alcohol consumption habits, basal health status and presentation features of syndrome were all recorded.

Data from 156 episodes of AWS that coursed without DTs were compared with 147 cases that coursed with it. Three independent variables for development of DTs were identified in a multivariate logistic regression model: number of seizures [1 or 2: OR 2.2 (CI 95% 1.2-3.8), p=0.005; 3 or more: OR 2.6 (CI 95% 1.04-6.8), p=0.04]; systolic blood pressure >150 mm Hg [OR 1.9 (CI 95% 1.1-3.8), p=0.03] and axillary temperature >38 degrees C [OR 1.9 (CI 95% 1.05-3.5), p=0.01]. ROC analysis revealed an area under the curve of 0.679.

Three clinical findings (seizures, blood pressure and temperature) can aid in identifying patients with AWS who are likely to develop DTs. The model's predictive capacity is not high.

Acute alcohol intoxication is a clinically harmful condition that usually follows the ingestion of a large amount of alcohol. Clinical manifestations are heterogeneous and involve different organs and apparatuses, with behavioral, cardiac, gastrointestinal, pulmonary, neurological, and metabolic effects. The management of an intoxicated patient occurs mainly in the emergency department and is aimed at stabilizing the clinical condition of the patient, depending on his/her clinical presentation. One specific drug that is useful in the treatment of acute alcohol intoxication is metadoxine, which is able to accelerate ethanol excretion. In patients presenting an acute alcohol intoxication, alcohol-related disorders should be detected so that the patient can be directed to an alcohol treatment unit, where a personalized, specific treatment can be established.

Alcohol withdrawal syndrome (AWS) can be a life-threatening condition affecting some alcohol-dependent patients who abruptly discontinue or decrease their alcohol consumption. The main objectives of the clinical management of AWS include: to decrease the severity of symptoms, prevent more severe withdrawal clinical manifestations and facilitate entry of the patient into a treatment program in order to attempt to achieve and maintain long-term abstinence from alcohol. At present, benzodiazepines represent the drugs of choice in the treatment of AWS. However, in line with the possible side effects and addictive properties related to benzodiazepine use, there is growing evidence to suggest that non-benzodiazepine GABAergic compounds represent promising medications in the treatment of alcohol-dependent patients. This review focuses on research into non-benzodiazepine GABAergic medications for the treatment of AWS. Among them, carbamazepine, gabapentin and valproic acid are the most studied. The studies on carbamazepine seem to be the most compelling. Preliminary data have also suggested the possible utility of baclofen and topiramate, although further evidence is needed. The promising results in terms of both safety and efficacy are reported. However, we also note the need of more methodologically controlled studies on a greater number of patients, involving more complicated forms of AWS.

Various factors that may influence the severity of the alcohol withdrawal syndrome (AWS) have been identified. We tested the predictive value of these factors compiled in a newly developed scale, LARS (Luebeck alcohol withdrawal risk scale).

A total of 100 individuals (81 males, 19 females, mean age: 47.6 +/- 9.9 years) consecutively transferred to inpatient detoxification were included in this prospective study. All fulfilled the ICD-10 criteria for alcohol dependence. The LARS was applied at the time of admission. The course of the AWS was assessed by AWS-scale at least every 4 h. The maximum AWS-score was taken as indicator of the severity of AWS.

The mean AWS-score(max) was 6.5 +/- 3.3. In all 20% of the patients developed a severe AWS (AWS-score(max) > or =10). The maximum score usually occurred within 36 h after the last drink. A short version, the LARS11, was developed by statistically grounded item reduction. The optimal cut-off of the LARS11 was calculated as 10. The positive predictive value for severe AWS was 76%, while the negative predictive value was 98.7%. The sensitivity and specificity were high (95 or 92.5%, respectively).

LARS11 assessed immediately before detoxification appears to provide a useful estimate of mild/moderate versus severe AWS, and is now ready to be validated in an independent sample.

Recent preclinical and clinical studies have suggested that baclofen, the prototypic gamma-aminobutyric acid B (GABA(B)) receptor agonist, is a promising pharmacological compound for use in the treatment of alcohol dependence. In particular, baclofen has been found to suppress symptoms of alcohol withdrawal syndrome with an efficacy comparable with that of the 'gold standard' diazepam. Moreover, baclofen has proven effective in the prevention of relapse due to its ability to reduce alcohol intake and craving in alcoholic patients. Baclofen proved to be manageable, producing no significant side effects and displaying no addictive properties. The efficacy of the drug in the management of both alcohol withdrawal syndrome and relapse prevention should entail a vastly simplified pharmacotherapy of alcohol dependence.

Benzodiazepines are the drugs of choice in the treatment of alcohol withdrawal syndrome (AWS). Recent data have shown that baclofen may reduce AWS symptoms. At present, no comparative studies between baclofen and any benzodiazepine used in AWS treatment are available. Accordingly, the present study was designed to compare efficacy, tolerability and safety of baclofen versus diazepam in the treatment of AWS.

Thirty-seven patients with AWS were enrolled in the study and randomly divided into 2 groups. Baclofen (30 mg/day for 10 consecutive days) was orally administered to 18 patients (15 males, 3 females; median age: 46.5 years). Diazepam (0.5-0.75 mg/kg/day for 6 consecutive days, tapering the dose by 25% daily from day 7 to day 10) was orally administered to 19 patients (17 men, 2 women; median age: 42.0 years). The Clinical Institute Withdrawal Assessment (CIWA-Ar) was used to evaluate physical symptoms of AWS.

Both baclofen and diazepam significantly decreased CIWA-Ar score, without significant differences between the 2 treatments. When CIWA-Ar subscales for sweating, tremors, anxiety and agitation were evaluated singly, treatment with baclofen and diazepam resulted in a significant decrease in sweating, tremors and anxiety score, without significant differences between the 2 drug treatments. Both treatments decreased the agitation score, although diazepam was slightly more rapid than baclofen.

The efficacy of baclofen in treatment of uncomplicated AWS is comparable to that of the "gold standard" diazepam. These results suggest that baclofen may be considered as a new drug for treatment of uncomplicated AWS.

A retrospective chart review was performed within an inpatient VA hospital setting in an attempt to identify risk factors for delirium tremens (DTs). Cases of delirium tremens were compared to cases where patients' alcohol withdrawal during hospitalization did not progress to DTs. Significant differences were found in regard to prior histories of DTs and laboratory values at admission. The amount and duration of benzodiazepine use during hospitalization, antipsychotic use during hospitalization, and length of hospitalization were also statistically different between the groups. While not reaching statistical significance, there were differences in reason for admission and relapse rate upon follow-up between the groups.