Alcohol withdrawal syndrome in ICU patients: Clinical features, management, and outcome predictors

Background Alcohol withdrawal syndrome (AWS) is a common condition in hospitalized patients, yet its epidemiology in the ICU remains poorly characterized. Methods Retrospective cohort of patients admitted to the Nantes University Hospital ICU between January 1, 2017, and December 31, 2019, and coded for AWS using ICD-10 criteria. The objective of the study was to identify factors associated with complicated hospital stay defined as ICU length of stay ≥7 days or hospital mortality. Results Among 5,641 patients admitted to the ICU during the study period, 246 (4.4%) were coded as having AWS. Among them, 42 had exclusion criteria and 204 were included in the study. The three main reasons for ICU admission were sepsis (29.9%), altered consciousness (29.4%), and seizures (24%). At ICU admission, median Cushman’s score was 6 [4–9] and median SOFA score was 3 [2–6]. Delirium tremens occurred in half the patients, seizures in one fifth and pneumonia in one third. Overall, 48% of patients developed complicated hospital stay, of whom 92.8% stayed in the ICU for ≥7 days, 36.7% received MV for ≥7 days, and 16.3% died during hospital stay. By multivariable analysis, two factors were associated with complicated hospital stay: a higher number of organ dysfunctions at ICU admission was associated with a higher risk of complicated hospital stay (OR, 1.18; 95CI, 1.05–1.32, P = 0.005), whereas ICU admission for seizures was associated with a lower risk of complicated hospital stay (OR, 0.14; 95%CI, 0.026–0.80; P = 0.026). Conclusions AWS in ICU patients chiefly affects young adults and is often associated with additional factors such as sepsis, trauma, or surgery. Half the patients experienced an extended ICU stay or death during the hospital stay. The likelihood of developing complicated hospital stay relied on the reason for ICU admission and the number of organ dysfunctions at ICU admission.

Barbiturates Versus Benzodiazepine for the Treatment of Severe Alcohol Withdrawal Syndrome: A Systematic Review and Meta-Analysis of Clinical Trials

Context: The utility of phenobarbital in the treatment of severe alcohol withdrawal is contentious. Objective: The aim was to conduct a meta-analysis of existing observational and randomized controlled trials investigating the efficacy and safety of phenobarbital versus commonly used benzodiazepine in the setting of severe alcohol withdrawal. Data Sources: A search of PubMed, Medline, Embase, and the Cochrane Central Register of Controlled Trials published between 1976 and September 2021 was performed using medical subject headings: “severe alcohol withdrawal”, “delirium tremens” (DT), “phenobarbital” (PB), “barbiturate”, “critical care”, “ICU”, “Trial”, “human” and “English”. We selected English-language clinical trials (observational and randomized controlled trials (RCT)) evaluating the efficacy and safety of phenobarbital (PB) compared to benzodiazepine (BZD) for the treatment of severe alcohol withdrawal syndrome (AWS) in the acute care setting. Study Appraisal and synthesis methods: Data extraction and critical appraisal were carried out independently by two authors (EC and YM) using predefined data fields. The outcome variables analyzed included (a) history of DT; (b) initial CIWA-AR score; (c) drug dosages delivered; (d) duration of medical treatment of severe AWS; (e) other adjunct medication use; (f) intensive care unit (ICU) length of stay (LOS); (g) hospital LOS; (h) readmission rate; (i) DT or seizures; (j) other complications including endotracheal intubation and mechanical ventilation. These outcomes were unanimously decided to be important as they influence the practical management of severe AWS within hospitals and institutions. Heterogeneity amongst the outcome variables of these trials was determined by Cochran’s Q statistics and I² index. The meta-analysis was prepared in accordance with PRISMA guidelines. Results: Seven studies consisting of 1 prospective RCT and 6 retrospective trials were identified. Results from all the included studies show similar variables between BZD and PB group: mean age, percentage of patients with previous DT, and median Clinical Institute Withdrawal Assessment for Alcohol Revised (CIWA-AR) scores. There were no statistically significant differences in ICU and hospital LOS when comparing the BZD and PB groups. The prevalence of DT and adjunct medication usage was higher in the BZD group; however, statistically insignificant in the meta-analysis. The pooled prevalence of intubation was similar between the two treatment groups. Lastly, Hawa et al. reported higher alcohol-related re-admission in the BZD group. Conclusions: Based on our findings, the use of PB as the primary treatment, or when used in addition/as adjunct to BZD, offers several advantages in the treatment of severe AWS. These include trend toward improved DT and seizures in severe AWS, shortened ICU and hospital LOS, and less use of adjunct medications. Further RCTs are needed to investigate PB as the primary treatment of AWS that presents with severe features.

Chronopharmacology of alcoholism

В статье представлен анализ информации из литературных источников, посвященной изучению хронофармакологии алкоголизма. Для лечения алкоголизма используется комплексный подход, определяющийся тяжестью состояния больного и индивидуальными особенностями симптоматики. В связи со способностью фармакологических соединений вмешиваться в течение ритмических процессов на всех уровнях организации биосистемы хронофармакологический эффект лекарственных средств может быть полезным или нежелательным. Высокой степенью осложнений со стороны сердечно-сосудистой и нервной систем, а также печени и желудочно-кишечного тракта характеризуется хроническая алкогольная интоксикация. Надежного средства патогенетической фармакотерапии алкоголизма до настоящего времени не разработано. При этом лекарственные препараты используют в основном для купирования явлений абстиненции. Одно из первых мест в терапии алкогольного абстинентного синдрома, сопровождающегося тревогой, страхом и беспокойством, занимают депримирующие средства. Однако расширение их применения в Российской Федерации для лечения алкоголизма остается необоснованным. Так как алкоголизм вызывает крайне разнообразные по своим клиническим проявлениям и по степени тяжести психические расстройства, то для их лечения используется широкий спектр психотропных препаратов. Для проведения противогипоксической и детоксифицирующей терапии используются энергокорригирующие средства. Алкогольный абстинентный синдром с преобладанием неврозоподобных и вегетативнососудистых расстройств является показанием к применению препаратов из класса антиоксидантов. Они сочетают в себе свойства транквилизаторов и ноотропов, не оказывая токсического воздействия на сердце и защищая миокард в условиях гипоксии. Однако на данный момент существует дефицит информации об эффективности их применения при алкогольной абстиненции. The article presents an analysis of information from literary sources devoted to the study of the chronopharmacology of alcoholism. For the treatment of alcoholism, an integrated approach is used, which is determined by the severity of the patient's condition and the individual characteristics of the symptoms. Due to the ability of pharmacological compounds to interfere during rhythmic processes at all levels of the organization of the biosystem, the chronopharmacological effect of drugs may be useful or undesirable. Chronic alcohol intoxication is characterized by a high degree of complications from the cardiovascular, nervous systems, liver and gastrointestinal tract. A reliable means of pathogenetic pharmacotherapy of alcoholism has not yet been developed. At the same time, medications are used mainly for the relief of withdrawal symptoms. One of the first places in the treatment of alcohol withdrawal syndrome, accompanied by anxiety, fear and anxiety, is occupied by depressants. However, the expansion of their use in the Russian Federation for the treatment of alcoholism remains unfounded. Since alcoholism causes extremely diverse mental disorders in their clinical manifestations and severity, a wide range of psychotropic drugs is used for their treatment. For antihypoxic and detoxifying therapy, energy-correcting agents are also used. Alcohol withdrawal syndrome with a predominance of neurosis-like and vegetative-vascular disorders is an indication for the use of drugs from the class of antioxidants. They combine the properties of tranquilizers and nootropics, without having a toxic effect on the heart and protecting the myocardium in hypoxia. However, at the moment there is a lack of information about the effectiveness of their use in alcohol withdrawal.

Comparative efficacy of various pharmacologic treatments of alcohol withdrawal syndrome: A systematic review and network meta-analysis

Review question / Objective: Lorazepam and other benzodiazepines (BZDs) are considered the first choice for treatment of Alcohol withdrawal syndrome (AWS). But they have significant addiction potential and can cause fatal respiratory depression if used in large doses. The aim of our study is to conduct a network meta-analysis to provide some data support for the clinical treatment of AWS. The patients were persons with alcohol withdrawal. The intervention being studied must be a comparison of the efficacy of the two pharmacologic treatments. The study should not be included if two pharmacologic treatments belonging to the same category were compared. All studies must include one of the following outcomes: Clinical Institute Withdrawal Assessment, revised (CIWA-Ar) score, length of hospital stay, length of intensive care unit (ICU) stay, and the incidence of delirium or seizures. Condition being studied: Side effects and safety of eleven types of agents currently used to treat alcohol withdrawal syndrome.