Characterization of alcohol-related seizures in withdrawal syndrome.

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.

Mortality and alcohol-related morbidity in patients with delirium tremens, alcohol withdrawal state or alcohol dependence in Norway: A register-based prospective cohort study.

BACKGROUND AND AIMS: Little is known about long-term consequences of delirium tremens (DT). This study aimed to compare all-cause and cause-specific mortality and alcohol-related morbidity between patients with: (i) DT, (ii) alcohol withdrawal state (AWS) and (iii) alcohol dependence (AD). DESIGN: A national longitudinal health registry study with linked data from the Norwegian Patient Registry and the Norwegian Cause of Death Registry. SETTING: Norway. PARTICIPANTS: All patients registered in the Norwegian Patient Registry between 2009 and 2015 with a diagnosis of AD (ICD-10 code F10.2), AWS (F10.3) or DT (F10.4) and aged 20-79 years were included (n = 36 287). MEASUREMENTS: Patients were categorized into three mutually exclusive groups; those with DT diagnosis were categorized as DT patients regardless of whether or not they had received another alcohol use disorder diagnosis during the observation period or not. Outcome measures were: annual mortality rate, standardized mortality ratios (SMR) for all-cause and cause-specific mortality and proportion of alcohol-related morbidities which were registered in the period from 2 years before to 1 year after the index diagnosis. FINDINGS: DT patients had higher annual mortality rate (8.0%) than AWS (5.0%) and AD (3.6%) patients, respectively. DT patients had higher mortality [SMR = 9.8, 95% confidence interval (CI) = 8.9-10.7] than AD patients (SMR = 7.0, 95% CI = 6.8-7.2) and AWS patients (SMR = 7.8, 95% CI = 7.2-8.4). SMR was particularly elevated for unnatural causes of death, and more so for DT patients (SMR = 26.9, 95% CI = 21.7-33.4) than for AD patients (SMR = 15.2, 95% CI = 14.2-16.3) or AWS patients (SMR = 20.1, 95% CI = 16.9-23.9). For all comorbidities, we observed a higher proportion among DT patients than among AWS or AD patients (P < 0.001). CONCLUSIONS: People treated for delirium tremens appear to have higher rates of mortality and comorbidity than people with other alcohol use disorders.

Seasonality and Delirium Tremens in Hospitalized Patients with Alcohol Dependence Syndrome.

INTRODUCTION: Due to the high rate of mortality, recognizing the contributing factors of alcohol-related delirium tremens (DT), which is the most severe form of alcohol withdrawal state (AWS) is pivotal in clinical settings. Previous studies suggested relationship between seasonality and other types of delirium; however, to our knowledge, this is the first empirical study which examined the role of seasonality in DT in alcohol dependence syndrome (ADS). METHODS: A retrospective study was undertaken between 2008 and 2015; medical records of 1,591 patients were included, which yielded 2,900 hospital appearances. Three groups were formed based on the ICD-10 diagnoses: ADS, AWS, and DT. The characteristics of the groups were analysed with one-way ANOVA and χ2 tests. Multinomial logistic regression was used to explore the potential predictors of DT, including seasonality. RESULTS: The highest incidence of DT was in spring (36.8%; χ2 (3) = 27.666; p < 0.001), especially in March (13.9%; χ2 (11) = 33.168; p < 0.001). Spring, higher mean age, higher presence of comorbid somatic disorders, and lower occurrence of comorbid psychiatric disorders were significant predictive variables for DT with the control of socio-demographic and clinical variables. CONCLUSIONS: The present study revealed that spring, especially March is a critical period in temperate climate zone regarding DT. This can be interpreted as a late winter effect since the temperature is lower in this month compared to other spring months. Furthermore, higher age and the occurrence of comorbid somatic disorders can be considered as risk factors in case of DT. These results support the need of further clinical studies to better understand the impact of seasonality on DT.

[Alcohol withdrawal delirium: What's new for an old disease?] / Delirium tremens : quoi de neuf pour une vieille maladie ?

The management of alcohol withdrawal syndrome is a frequent work in both community medicine and hospital wards. One of the most severe complications of alcohol withdrawal is Delirium Tremens (DT). The purpose of this development is to update knowledge on this complication in terms of diagnosis, evaluation and therapeutic approaches. It also proposes a reflection on the trajectory of care during and after DT.

Derivation and validation of a multivariable model, the alcohol withdrawal triage tool (AWTT), for predicting severe alcohol withdrawal syndrome.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Phenomenology and Course of Alcoholic Hallucinosis.

Objective: The objective of the study was to examine the correlates, phenomenology, and short-term treatment response to benzodiazepines and antipsychotics in an inpatient sample with alcohol-induced psychotic disorder, predominant hallucinations i.e., F10.52. Methods: We reviewed the charts of the patients admitted in a tertiary care addiction treatment center between 2010 and 2016 with the diagnosis of alcoholic hallucinosis. Results: Among 6,493 patients admitted with alcohol dependence during the study period, 61 patients (0.9%) had alcoholic hallucinosis. Among them, 41 (67.2%) had alcoholic hallucinosis in the past; 26 (42.6%) had a family history of psychosis. Only auditory hallucinations were found in 46 patients (75.4%), only visual hallucinations in 3 patients (5%), and both auditory and visual hallucinations in 12 (19.7%). Thirty-four (55.7%) had delusions, which were secondary to hallucinations. Suicidality which includes suicidal ideas and attempts was noted in 12 (19.7%) patients. Fifty-three (86.9%) patients had hallucinations exclusively during alcohol withdrawal, while 8 (13.1%) had them during withdrawal as well as while consuming alcohol. At the end of six months, 13.1% of the patients had an independent psychotic disorder diagnosed. The primary mode of management was treatment with only benzodiazepines (n = 37, 60.7%) or benzodiazepines and antipsychotics (n = 24, 39.3%). The reasons for starting antipsychotics were the presence of florid psychotic symptoms (26.2%) and incomplete symptom resolution with benzodiazepines (9.8%). The median duration of response was four days, with 25th to 75th quartile range at two to seven days. Conclusions: Alcoholic hallucinosis is an acute short-lasting psychotic disorder which lasts for less than a week when treated. Suicidality is high in this group, which needs attention. Benzodiazepines as part of withdrawal management may be sufficient for a majority of cases. Antipsychotics may be required in selected cases. A high degree of recurrence and morbidity indicates a need to intervene early with an abstinence-oriented management goal.

Pellagra and Alcohol Dependence Syndrome: Findings From a Tertiary Care Addiction Treatment Centre in India.

AIM: To define the prevalence and clinical presentation of pellagra, a multi-systemic disease caused by the deficiency of niacin, in patients admitted to a tertiary addiction treatment centre in southern India, with alcohol dependence syndrome (ADS)-(ICD10). METHODS: Review of the health records of 2947 patients who received inpatient care for ADS between 2015 and 2017. RESULTS: Out of 2947, 31 (1%) were diagnosed with pellagra. Nearly two-thirds (64.5%) of those with pellagra were from a low-income group. Of the clinical-triad of pellagra, all patients had dermatitis, more than half (58%) had delirium, a minority (19%) had diarrhoea. Nearly two-thirds (61%) had presented in a complicated-withdrawal state. Associated conditions included peripheral neuropathy (32%); Wernicke's encephalopathy (26%); seizures (16%).Seventeen (54%) had BMI <18.5 kg/m2. Treatment was a high dose of parenteral vitamins including niacin (mean dose: 1500 mg/day) for an average of 7.5 days followed by oral multivitamin supplements. All had complete resolution of pellagrous symptoms by the end of the three weeks of inpatient care. CONCLUSIONS: Pellagra is an acute medical condition, frequently encountered in the context of alcohol dependence and poverty. It often presents with other disabling and life-threatening comorbidities like delirium tremens and Wernicke's encephalopathy. The classical triad of pellagra is only seen in a minority of cases. Thus a high index of suspicion is required lest pellagra may remain undiagnosed. Prompt identification and treatment with a high dose of niacin in combination with other vitamins result in complete recovery.

Alcohol and delirium tremens: effects of average number of drinks per day and beverage type.

OBJECTIVE: Associations of amount of alcohol intake and beverage type with the risk of delirium tremens (DT) have not been studied. This longitudinal study investigated if the average number of drinks per day and beverage type predict DT. METHODS: A cohort of 3 582 alcohol-dependent men and women aged 19-82 without previous DT were interviewed about alcohol intake and beverage type at baseline in 1994-2005 and followed through record linkage in Danish nationwide registers to identify incident DT. Data were analyzed by means of Cox regression models. RESULTS: An average number of drinks per day of 20-30 or >30 was associated with hazard ratios (HRs) of 1.38 (95% CI 1.03-1.84) and 1.64 (95% CI 1.19-2.27) relative to the reference category (1-9 drinks). Independently of amount consumed and covariates (age, gender, civil status and work status), beverage type (spirits vs. mixed alcohol) was associated with a HR of 1.63 (95% CI 1.08-2.46). Male gender was robustly associated with increased risk (HR = 1.62 (95% CI 1.25-2.08). CONCLUSIONS: In alcohol-dependent men and women, daily alcohol intake above a threshold of 20 beverages or 240 g alcohol and a preference for spirits increase the risk of developing DT.

Election bans and alcohol banes: The impact of elections on treatment referrals at a tertiary addiction treatment facility in India.

Pattern of alcohol use and its related complications is determined by multiple factors. We studied the effects of sudden ban of alcohol during elections in a state of India. We found that unexpected election bans could lead to severe complications in alcohol dependent individuals. Impact of sudden policy changes needs to be thought prior to implementation.

Incidence rates of admissions associated with alcohol withdrawal syndrome in Spain: Analysis of minimum basic data set 1999-2010. / Tasas de incidencia de ingresos asociados a síndrome de abstinencia alcohólica en España: análisis del conjunto mínimo básico de datos 1999-2010.

BACKGROUND: There are no data on the incidence of admissions associated with alcohol withdrawal syndrome (AWS) or about its trend over time in Spain. OBJECTIVE: To analyze the characteristics, incidence rates and trends over time of hospital admissions associated with AWS in Spanish public hospitals. MATERIAL AND METHOD: Analysis from the Spanish public hospitals minimum basic data set of hospital admissions with AWS (CIE9-MC 291.81), alcohol withdrawal delirium (CIE9-MC 291.0) and alcohol withdrawal hallucinosis (CIE9-MC 291.3), since 1999 to 2010. RESULTS: We identified 56,395 admissions associated with AWS. Mean age was 50.9 (SD 12.5) and 88% were male. The most frequent admission department was Internal Medicine (24.9%). The mean hospital stay was 12.6 days (SD 14.4) and mortality was 4.7%; 62.6% of cases developed AWS during an admission for another reason, mostly due to alcohol-related pathologies. Secondary diagnoses in patients hospitalized for AWS were related to alcohol consumption in more than half of the cases. The incidence rate of admissions associated with AWS in Spain remained stable from 1999 to 2010, with a small decline in the last 3 years of the period. The communities with the highest incidence were the Canary Islands, the Balearic Islands and Galicia. CONCLUSIONS: The incidence rate of admissions associated with AWS in Spanish public hospitals in the period 1999-2010 has remained stable with slight changes. There are differences in the incidence of AWS among the different autonomous communities.

Delirium tremens and alcohol withdrawal nationally in the Veterans Health Administration.

BACKGROUND AND OBJECTIVES: Alcohol withdrawal-especially delirium tremens (DT)-is a potentially life-threatening condition. While short-term treatment regimens and factors that predispose to more severe symptomatology have been extensively studied, little attention has been paid to the clinical epidemiology and long-term care of the chronic medical, addictive, psychiatric, and psychosocial problems faced by these patients. METHODS: National Veterans Health Administration data from fiscal year 2012 were examined to identify veterans diagnosed with DT; with withdrawal but not DT (WNDT); and with Alcohol Use Disorder (AUD) but neither DT nor WNDT. They were compared on sociodemographic characteristics, psychiatric and medical co-morbidities, and health service and psychotropic medication use, first with bivariate analyses and then multiple logistic regression. RESULTS: Among the 345,297 veterans diagnosed with AUD, 2,341 (0.7%) were diagnosed with DT and 6,738 (2.0%) with WNDT. Veterans diagnosed with either WNDT or DT were more likely to have been homeless, had more comorbid medical and psychiatric disorders, were more likely to be diagnosed with drug use disorders, utilized more health services, received more psychotropic medications, and were more likely to receive naltrexone. They were more likely to receive specialized legal, housing, vocational, and psychosocial rehabilitation services, as well as intensive case management. CONCLUSIONS: Adults with WNDT and DT suffer from multiple chronic conditions and long-term service models are needed to coordinate the work of multiple specialists and to assure continuity of care. SCIENTIFIC SIGNIFICANCE: This national study identifies sociodemographic characteristics, comorbidities, and service utilization patterns associated with WNDT and DT.(Am J Addict 2017;26:722-730).

Occurrence, Predictors, and Prognosis of Alcohol Withdrawal Syndrome and Delirium Tremens Following Traumatic Injury.

OBJECTIVES: We sought to determine occurrence, predictors, and prognosis of alcohol withdrawal syndrome and delirium tremens in patients with traumatic injury. DESIGN: Retrospective multicenter cohort study. SETTING: Three U.S. trauma centers. PATIENTS: Twenty-eight thousand one hundred one trauma patients admitted from 2010-2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures included occurrence of alcohol withdrawal syndrome and delirium tremens, injury characteristics, risk factors for alcohol withdrawal syndrome, clinical outcomes, pharmacologic treatment for alcohol withdrawal syndrome, and Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar) scores. Alcohol withdrawal syndrome severity was defined by CIWA-Ar score as minimal (< 10), moderate (10-20), and severe (> 20). Alcohol withdrawal syndrome developed in 0.88% (n = 246), including 12% minimal, 36% moderate, and 53% severe. Alcohol withdrawal syndrome progressed to delirium tremens in 11%. Before adjustment, alcohol withdrawal syndrome severity was associated with injury severity, hypokalemia, baseline CIWA-Ar score, and established alcohol withdrawal syndrome risk factors. Logistic regression identified the following predictors of delirium tremens: baseline CIWA-Ar score greater than or equal to 10 (odds ratio, 6.05; p = 0.02) and age greater than or equal to 55 (odds ratio, 3.24; p = 0.03). In patients with severe alcohol withdrawal syndrome, severe head injury also predicted progression to delirium tremens (odds ratio, 6.08; p = 0.01), and hypokalemia was borderline significant (odds ratio, 3.23; p = 0.07). Clinical outcomes of hospital length of stay, ICU length of stay, and alcohol withdrawal syndrome complications differed significantly by alcohol withdrawal syndrome severity and were worse with more severe manifestations of alcohol withdrawal syndrome. Mortality also significantly differed by alcohol withdrawal syndrome severity but was only greater in patients who progressed to delirium tremens (11.1%; p = 0.02); otherwise, there were no differences in mortality by severity (4%, 4%, and 0% by minimal, moderate, and severe alcohol withdrawal syndrome). CONCLUSIONS: Trauma patients with alcohol withdrawal syndrome experience a high occurrence of delirium tremens that is associated with significant mortality. These data demonstrate the predictive ability of baseline CIWA-Ar score, age, and severe head injury for developing delirium tremens.

[Alcoholism at the end of 1980-s and beginning of 2010-s]. / Alkogolizm v kontse 1980-kh i nachale 2010-kh godov.

AIM: To study the 20-years' clinical alteration and alcoholism basing on the changes in its clinical symptoms and course. MATERIAL AND METHODS: The study included 527 alcoholics with formed alcohol withdrawal syndrome: 181 alcoholics were examined in 1988-1990 (Group 1) and 346 alcoholics in 2011-2012 (Group 2). RESULTS AND CONCLUSION: In Group 1, vodka consumption dominated at all stages of alcoholism. Group 2 included 172 alcoholics with the domination of vodka consumption and 174 alcoholics with mixed consumption. It was shown that in comparison with Group 1 (1988-1990 patients) patients from Group 2 (2011-2012) had slower and mild development of alcoholism, especially those in the mixed consumption group. The authors suggest that the change of the clinical pattern in Group 2 was due to the change in the composition of consumed alcoholic beverages.

Assessment of Withdrawal and Hangover is Confounded in the Alcohol Use Disorder and Associated Disabilities Interview Schedule: Withdrawal Prevalence is Likely Inflated.

BACKGROUND: The Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV (AUDADIS-IV) and AUDADIS-5 are diagnostic interviews used in major epidemiological and other studies of alcohol use disorder (AUD). Much of what we know regarding the prevalence of AUD in the United States is based upon this interview. However, past research and meta-analytic evidence suggest that differential operationalization of the AUD criteria across instruments can lead to differential endorsement of symptoms and resulting AUD diagnosis rates. In particular, studies employing the AUDADIS are observed to have markedly higher endorsement rates of withdrawal than other large epidemiological studies. One explanation for this is that when assessing withdrawal, the AUDADIS combines effects from the morning after drinking with those from the days following, thereby conflating hangover and withdrawal. METHODS: This study addresses whether this operationalization confounds rates of endorsement when compared to simpler, less ambiguous hangover or withdrawal stems. To this aim, 497 college student drinkers were randomized into 1 of 3 stem conditions: (i) hangover (n = 164), (ii) withdrawal (n = 167), or (iii) combined AUDADIS-IV (n = 166). RESULTS: Across conditions, participants were more likely to report the occurrence of each withdrawal symptom in the combined stem condition than in the explicit withdrawal stem condition, but not in the explicit hangover stem condition. Within the combined stem condition, probed symptoms were more likely to be reported as a result of a hangover. CONCLUSIONS: The AUDADIS potentially results in false positives for withdrawal, arguably a pathognomonic symptom of alcoholism and, in turn, likely affects rates of the diagnosis of AUD.

[Comparison of Two Symptom-Triggered Treatments for Alcohol Withdrawal: HAES vs. SAB-P]. / Zwei Alkoholentzugsscores im Vergleich: Hamburger Alkoholentzugs-Skala (HAES) vs. Scoregesteuerte Alkoholentzugsbehandlung nach Rating durch das Pflegepersonal (SAB-P).

INTRODUCTION: For alcohol withdrawal during hospitalization, often a medication as means for withdrawal needs to be chosen. Modern, score-controlled processes that can be used by the nursing staff after instruction by physicians are frequently not used and even unknown in hospitals. One reason for this is that some of the scores require checking several criteria and are therefore more time-consuming and complicated than use of a fixed-dosage strategy. The SAB-P and HAES are short with only 6 items that can be checked by the nursing staff. METHODS: Safety of the Hamburg Alcohol Withdrawal Scale (Hamburger Alkoholentzugs-Skala (HAES)) was analyzed retrospectively and prospectively with regard to score-controlled alcohol-withdrawal treatment after rating by the nurse staff (Scoregesteuerte Alkoholentzugsbehandlung nach Rating durch das Pflegepersonal (SAB-P)). RESULTS: Incidence of complications in patients treated with SAB-P and HAES was nearly similar with 1% start of delirium and 3% seizures (SAB-P) and 0.5 to 1.5% start of delirium and 0 to 0.5% seizures in the HAES group. With both scales it was possible to start medical treatment while still under falling alcohol levels (0.93 and 0.91%, respectively). Medication dosage was initially higher using the HAES, so that the time needed to monitor withdrawal symptoms could be reduced (3.8 vs. 3.1 days). DISCUSSION: Using a score-controlled strategy for alcohol withdrawal leads to a lower complication rate than found in literature. The structured procedure was helpful for the nursing staff as well as for the physicians. SAB-P as well as HAES made withdrawal for the patients more comfortable and led to fewer complaints. Because of rapid reaction and faster symptom reduction of HAES, there was less time necessary for monitoring. Simple handling, clomethiazol, oxazepam or diazepam as applicable medication and clear documentation are the advantages of HAES.

[Combination of DAT and DBH gene polymorphisms with a family history of alcohol use disorders increases the risk of withdrawal seizures and delirium tremens during alcohol withdrawal in alcohol-dependent men]. / Sochetanie polimorfizma genov DAT i DBH s semeinoi otyagoshchennost'yu po alkogol'noi zavisimosti uvelichivaet risk razvitiya sudorozhnykh pristupov i alkogol'nykh psikhozov u muzhchin.

AIM: To explore the genetic influence of a family history of alcohol use disorders and the dopamine transporter SLC6A3 (DAT1) and dopamine beta-hydroxylase (DBH) gene polymorphisms on the risk of severe complications (withdrawal seizures (AWS) and delirium tremens (DT)) during alcohol withdrawal in alcohol-dependent men. MATERIAL AND METHODS: We investigated the effects of 3 previously reported candidate genetic variations: 40-bp variable number tandem repeat (VNTR) polymorphism and C/T exon 15 (rs27072) in the 3' untranslated region (3' UTR) of the SLC6A3(DAT1) gene, and -1021 C/T (rs1611115) of DBH gene in 266 alcohol-dependent Russian male inpatients in two groups by presence (SC group: AWS, DT, AWS+DT, n=130) or absence (n=136) of severe complications diagnosed by ICD-10 during current alcohol withdrawal. Clinically important information and a family history of alcohol use disorders (FH) were obtained by semi-structured interview. RESULTS: Patients in SC group more often have positive FH (54.6% vs. 33%, p=0.001) and their age at first alcohol use (FAU) was lower (16±3.53y.o vs. 17±1.66 y.o, p=0.001). Logistic regression revealed that FH predicts severe complications in total (р=0.001) and DT (р=0.003), FAU independently predicts severe complications in total (р=0.008), AWS (р=0.04), DT (р=0.032), AWS+DT (р=0.048) and every year of delay alcohol use decreases the risk by 18-30%. The gene polymorphisms interact with FAU to decrease the FAU influence on the risk of AWS (T variant of DAT (rs27072), р=0.04), (AWS+DT) and DT (T variant of DBH (rs1611115), р=0.023 and р=0.06). The T variant of DAT (rs27072) is associated with FAU (p=0.007) and increases the risk of (AWS+DT) (р=0.036), but decreases the risk of AWS (р=0.038) and of DT (р=0.021) too, but only in interaction with positive FH. The 9 repeat variant (9R) of DAT VNTR is associated with AWS (p=0.009), but the risk of AWS (р=0.004) and of SC in total (р=0.001) are elevated only in 9R carriers with positive FH. The 9R independently increases the risk of DT (р=0.048) and the effect become more robust in 9R carriers with high density of FH (р=0.014). The gene x gene interaction decreases the risk of DT (р=0.055). According to an analysis of total cohort of patients, the T variant of DBH (rs1611115) is associated with any kind of manifestation of delirium in alcohol-dependent men (p=0.039). CONCLUSION: This study demonstrate the genetic influence of a family history of alcohol use disorders and DAT and DBH gene polymorphisms on the risk of withdrawal seizures and delirium tremens. The interaction of genetic variations with positive family history provides the most robust effect, the interaction of genetic variations with the age at first alcohol use may «protect¼ their carriers from negative influence of this «behavioral¼ risk factor. Replication in large cohorts of patients is necessary to verify these findings for subsequent use in prevention programs.

Multicenter evaluation of pharmacologic management and outcomes associated with severe resistant alcohol withdrawal.

INTRODUCTION: A subset of patients with alcohol withdrawal syndrome does not respond to benzodiazepine treatment despite escalating doses. Resistant alcohol withdrawal (RAW) is associated with higher incidences of mechanical ventilation and nosocomial pneumonia and longer intensive care unit (ICU) stay. The objective of this study is to characterize pharmacologic management of RAW and outcomes. METHODS: Adult patients were identified retrospectively via International Classification of Diseases, Ninth Revision codes for severe alcohol withdrawal from 2009 to 2012 at 3 hospitals. Data collected included pharmacologic management and clinical outcomes. RESULTS: A total of 184 patients met inclusion criteria. Sixteen medications and 74 combinations of medications were used for management. Propofol was the most common adjunct agent, with dexmedetomidine and antipsychotics also used. One hundred seventy-five patients (96.2%) were admitted to the ICU, with 149 patients (81.9%) requiring ventilator support. Median time to resolution of alcohol withdrawal syndrome from RAW designation was 6.0 days. Median ICU and hospital length of stay were 9.0 and 12.7 days, respectively. CONCLUSION: Diverse patterns exist in the management of patients meeting RAW criteria, indicating lack of refined approach to treatment. High doses of sedatives used for these patients may result in a high level of care, illustrating a need for evidence-based clinical guidelines to optimize outcomes.