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Introdução: Quando os consumidores excessivos crónicos de álcool, particularmente os indivíduos com o diagnóstico de perturbação de uso de álcool, suspendem abruptamente o consumo de bebidas alcoólicas, pode surgir um quadro clínico denominado síndrome de abstinência alcoólica. Nestes casos, é necessário muitas vezes instituir tratamento farmacológico para aliviar os sintomas e prevenir as complicações da abstinência. O tratamento farmacológico da síndrome de abstinência alcoólica é utilizado em unidades especializadas no tratamento de perturbação de uso de álcool, mas também pode ser necessário em serviços médico-cirúrgicos, quando esta síndrome se manifesta em doentes com perturbação de uso de álcool internados por patologias orgânicas.Métodos: Revisão de guidelines disponíveis na literatura sobre tratamento da síndrome de abstinência alcoólica com o objetivo de determinar qual o tratamento farmacológico recomendado.Resultados: Foram analisadas as quatro guidelines sobre tratamento farmacológico da síndrome de abstinência alcoólica (National Institute for Health and Care Excellence, American Society of Addiction Medicine, World Federation of Societies of Biological Psychiatry e American Psychiatric Association), em relação às suas recomendações e evidência da eficácia dos fármacos para tratamento da síndrome de abstinência alcoólica. Esta análise foi ainda complementada pela consulta das guidelines de Maudsley.Discussão: As guidelines analisadas recomendam, como tratamento de primeira linha, o uso de benzodiazepinas. A associação de anticonvulsivantes, agonistas adrenérgicos alfa-2, betabloqueantes e antipsicóticos com benzodiazepinas está recomendada para controlo sintomático em quadros de privação mais exuberantes. É recomendado administrar tiamina para profilaxia da encefalopatia de Wernicke-Korsakoff a todos os doentes. Caso existam desequilíbrios hidroelectrolíticos, estes deverão ser corrigidos.Conclusão: É fundamental manter um nível elevado de suspeita para o eventual aparecimento da síndrome de abstinência alcoólica em todos os contextos clínicos. Nesses casos, importa saber intervir precocemente.

The article deals with the provision of medical care to the patients with alcohol withdrawal state. The findings on the effectiveness of Armadin use in the comprehensive treatment of these patients compared to patients who received only basic therapy are presented. It is shown that the drug has vegetostabilizing, tranquilizing effect, significantly reduces the symptoms of alcoholic polyneuropathy, normalizes the levels of liver enzymes in the blood. Armadin in patients with alcohol withdrawal syndrome reduces the appearance of positive symptoms and accelerates the process of its leveling, which can be associated with both a triple mechanism of action of the drug (hepatoprotective, nootropic, antioxidant), and its influence on dopamine levels., В статье рассматривается вопрос оказания медицинской помощи пациентам с состоянием отмены алкоголя. Представлены данные исследования эффективности применения препарата Армадин в комплексном лечении таких больных в сравнении с пациентами, получающими только базисную терапию. Показано, что препарат оказывает вегетостабилизирующее, транквилизирующее действие, существенно снижает проявления алкогольной полинейропатии, нормализует уровень печеночных ферментов в крови. При применении препарата Армадин у пациентов с синдромом отмены алкоголя уменьшаются проявления продуктивной симптоматики и ускоряется процесс ее нивелирования, что может быть связано как с тройным механизмом действия препарата (гепатопротекторное, ноотропное, антиоксидантное), так и с его влиянием на уровень дофамина., У статті розглядається питання надання медичної допомоги пацієнтам зi станом відміни алкоголю. Наведено дані дослідження щодо ефективності застосування препарату Армадин у комплексному лікуванні таких хворих порівняно з пацієнтами, які отримують тільки базисну терапію. Показано, що препарат має вегетостабілізуючу, транквiлiзуючу дію, істотно знижує прояви алкогольної полінейропатії, нормалізує рівень печінкових ферментів у крові. При застосуванні препарату Армадин у пацієнтів iз синдромом відміни алкоголю зменшуються прояви продуктивної симптоматики і прискорюється процес її нівелювання, що може бути пов’язано як iз потрійним механізмом дії препарату (гепатопротекторна, ноотропна, антиоксидантна), так і з його впливом на рівень дофаміну.

Background Alcohol withdrawal syndrome (AWS) is an uncommon occurrence in trauma victims. However, the syndrome can cause a prolonged hospital stay. Therefore, the purpose of this study is to develop and validate the risk factors of AWS so that interventions can be applied to high-risk patients. Methods All adult trauma patients with an injury severity score of ≥1 and greater than one hospital day were included in the study. The Trauma Quality Improvement Program (TQIP) database from 2013-2016 was accessed for the study. Patient demography, injury and comorbidities were compared between the patients who developed AWS and who did not develop AWS. The data were split into 2 datasets: training and testing. Eighty percent (80%) of the data was randomly selected for the training dataset to develop the risk factors. The remaining 20% of the data were used for validation of the risk factors using multivariable analysis. The receiving operating characteristics (ROC) curve and area under the curve (AUC) were generated for model fitness. All P values Results A total of 497,819 patients qualified for the study. Only 6,894 (1.38%) patients developed AWS during their hospitalization. The median age of the patients, who developed AWS, was 54 years. The patients were predominantly male (84% vs. 63.1%) and Caucasian (80.3% vs. 76.1%). The multivariable analysis showed an age range of 45 years to 74 years old, male gender, Caucasian race, a history of chronic alcoholic abuse, hypertension and cirrhosis increased the risk of AWS. The AUC of the model of 0.910, 95% CI; [0.901, 0.918] showed an excellent model for predicting the risk of the development of AWS. Conclusion Approximately 1.4% of the trauma victims developed AWS. Certain patient demographic and comorbidity characteristics, and head injury have a higher risk of developing of AWS.

In the United States, alcohol is the most common substance used and the spectrum of unhealthy alcohol use is highly prevalent. Complications of unhealthy alcohol use affect nearly every organ system. One of the most frequent and potentially life-threatening of these complications is alcohol withdrawal syndrome for which benzodiazepines remain first-line therapy. Pharmacologic treatment of alcohol use disorder, the most severe form of unhealthy alcohol use, is underutilized despite the availability of multiple effective medications. Although behavioral therapies are an important component of treatment, they are overemphasized at the expense of pharmacotherapy.

Funding Information: This study was funded by Fundação Ciência e Tecnologia, IP national support through CHRC (UIDP/04923/2020). Publisher Copyright: Copyright © 2023 Azevedo, Neto, Gama, Subtil, Fuertes, Pereira, Tavares, Medinas, Silva and Dias. Introduction: Alcohol-related problems disproportionally affect people experiencing homelessness. As the first wave of the COVID-2019 pandemic spread in 2020, a number of emergency shelters were opened in Lisbon. Increased difficulties in obtaining alcohol could have led to an increased incidence of alcohol withdrawal. Therefore, a low-threshold harm reduction intervention was introduced to these emergency shelters. This consisted of a fixed medication treatment, made available immediately for those with specific conditions, without the need for a medical evaluation or abstinence from alcohol, together with an offer of subsequent access to specialized addiction centers. The Problemas Ligados ao Álcool em Centros de Emergência (PLACE) study (alcohol-related problems in emergency shelters) is a retrospective mixed-methods observational study. It describes the demographic, health, and social characteristics of shelter users participating in the program and aims to evaluate the intervention as well as the experience of the patients, professionals, and decision-makers involved. Results: A total of 69 people using shelters self-reported alcohol-related problems. Among them, 36.2% of the people accepted a pharmacological intervention, and 23.2% selected an addiction appointment. The take-up of the intervention was associated with better housing outcomes. A description of an individual's trajectory after leaving the shelter is provided. Discussion: This study suggests that non-abstinence-focused interventions can be useful and well-tolerated in treating addiction in this population. publishersversion published

BACKGROUND: Alcohol use disorder (AUD) is a major public health concern in South Africa (SA). Abrupt cessation or reduction of alcohol intake in chronic users can result in withdrawal symptoms. Benzodiazepines are the treatment of choice but need to be used cautiously in patients with a lifetime history of substance abuse given their highly addictive potential. Symptom-triggered prescription of benzodiazepines during alcohol withdrawal using the Revised Clinical Institute Withdrawal for Alcohol Scale (CIWA-Ar) has been associated with improved safety and reduced benzodiazepines use. AIM: To investigate if implementation of the CIWA-Ar during alcohol detoxification impacted the dose of benzodiazepines used and withdrawal-related outcomes. SETTING: Alcohol rehabilitation unit (ARU) at Stikland Psychiatric Hospital. METHODS: A retrospective cohort study of 135 admissions over a six-month period comparing two groups: before (2015) and after (2017) the implementation of the CIWA-Ar. RESULTS: The study noted no differences in sociodemographic and alcohol-associated variables between the two groups, and there were no recorded complications in either group. The 2017 group had a lower percentage of patients that required benzodiazepines (33.8% vs. 51.4%, p = 0.04) and a lower median total amount of benzodiazepines used during alcohol withdrawal (0 mg vs. 5 mg, p = 0.01). CONCLUSIONS: The CIWA-Ar rating scale was an effective alternative to prescribing benzodiazepines pro re nata and decreased the total dose of benzodiazepines used during alcohol withdrawal. CONTRIBUTION: The use of a symptom triggered regime, like the CIWA-Ar rating scale, during withdrawal can be implemented safely in a SA treatment setting for patients with low-risk AUD.

Background: Alcohol use disorder represents a serious health problem worldwide which is increasing in pervasiveness. Alcohol withdrawal syndrome is a common clinical problem encountered in emergency departments and inpatient settings, including intensive care units. While benzodiazepines are the most widely used class of medication for the treatment of alcohol withdrawal, in recent years, there is renewed interest in using phenobarbital, a barbiturate, in the treatment of refractory alcohol withdrawal. Objective: This review provides an overview of phenobarbital in the treatment of alcohol withdrawal, as well as clinical outcomes in patients, while also outlining some of the limitations of existing studies in comparing phenobarbital to benzodiazepines. Methods: PubMed, Ovid MEDLINE, and Cochrane databases were searched using the terms phenobarbital, barbiturates, and alcohol withdrawal syndrome. Prospective and retrospective trials comparing phenobarbital with benzodiazepines to treat alcohol withdrawal in English were included. Results: Two prospective randomized controlled and eleven retrospective cohort trials were identified. Phenobarbital is safe alone and as an adjunct to benzodiazepine in the emergency department, intensive care units, general medical units and acute trauma surgery service. In a randomized controlled trial, one dose of phenobarbital in the emergency department significantly reduced the intensive care admission rate. There is some evidence that phenobarbital may be effective in the treatment of benzodiazepine- refractory alcohol withdrawal. Conclusion: Although existing knowledge and practice regarding phenobarbital for the treatment of alcohol withdrawal are increasing, there currently remains limited evidence in support of phenobarbital over benzodiazepines in superior efficacy and outcomes.

Background Atrial arrhythmias are commonly noted in patients with alcohol withdrawal syndrome (AWS), requiring inpatient admission. Objective The burden of arrhythmias and the association with in-hospital outcomes are incompletely defined in patients hospitalized with AWS. Methods The nationwide inpatient sample database was accessed from September 2015 to December 2018 to identify hospitalizations for AWS. We studied a cohort of patients with arrhythmias noted during hospitalization using the appropriate International Classification of Diseases, Tenth Revision billing codes. We compared patient characteristics, outcomes, and hospitalization costs between alcohol withdrawal hospitalizations with and without documented arrhythmias. Propensity score matching (PSM) and multivariate regression were performed to control confounders and develop odds ratios (OR), respectively. Results Among 1,511,155 hospitalization with AWS, 146,825 (9.72%) had concurrent arrhythmias. After PSM, we identified 135,540 cases in each group. Hospitalizations with AWS and concurrent arrhythmias had higher in-hospital mortality (4.19% vs 1.95%, OR 1.76, confidence interval [CI] 1.67–1.85, P < .0001). The most common arrhythmia was atrial fibrillation (66.7%). Arrhythmias in AWS were also associated with poorer in-hospital outcomes, including a higher risk of acute heart failure (8.40% vs 4.58%, OR 1.97, CI 1.90–2.05, P < .0001), acute kidney injury (21.32% vs 15.27%, OR 1.39, CI 1.36–1.43, P < .0001), and acute respiratory failure (9.19% vs 5.49%, OR 1.70, CI 1.64–1.76, P < .0001) requiring intubation. The length of hospital stay (6 days vs 4 days P < .0001) and cost of hospital care ($12,615 [$6683–$27,330] vs $7860 [$4482–$15,868], P < .0001) were higher in AWS with arrhythmias. Conclusion Arrhythmia in AWS is associated with higher in-hospital mortality and poorer in-hospital outcomes.

The literature review presents modern ideas about the place of neuroleptics in the treatment of mental and behavioural disorders due to the use of alcohol from the standpoint of evidence-based medicine. It has been shown that only few neuroleptics have proven anti-alcohol/antiopioid efficacy, namely tiapride, haloperidol, and chlorprothixen, which are included in clinical guidelines and relevant protocols in the United States and Europe. It has been determined that tiapride has the necessary effects for the treatment of alcohol withdrawal syndrome and for the use as an anti-craving agent in anti-relapse treatment.

Alcohol withdrawal is the most threatening condition encountered in patients with alcohol use disorder. Our study aimed to investigate the association of alcohol withdrawal severity with polymorphic variants in melatonin receptor genes. Methods. The clinical study was carried out on the basis of the Republican Narcological Dispensary №1 in Ufa and the Republican Narcological Dispensary №2 in Sterlitamak. Genetic analysis was performed at the Department of Personalised Psychiatry and Neurology at the V.M. Bekhterev Research Centre, Saint Petersburg. The final sample consisted of 307 subjects. Results. Carriers of the TT genotype of the MTNR1A gene (rs34532313) were found to have less hypertension during alcohol withdrawal than carriers of the other genotypes. In comparison, carriers of the GG genotype of the MTNR1B gene (rs10830963) experienced more symptoms than other genotypes: paroxysmal sweating, visual hallucinations, anxiety, and overall CIWA-Ar score. Conclusions. Thus, it can be concluded that the TT genotype of MTNR1A gene (rs34532313) is associated with a lower risk of hypertension during alcohol withdrawal compared to carriers of other gene genotypes. The GG genotype of MTNR1B gene (rs10830963) is associated with severe withdrawal. In general, it can be concluded that melatonin receptors are involved in the pathogenesis of alcohol withdrawal and the severe of some of its symptoms.

Rationale: Several institutions have implemented phenobarbital-based pathways for the treatment of alcohol withdrawal syndrome (AWS). However, little is known about the care processes, effectivenes...

Objective Pheochromocytoma (PCC) crisis caused by acute catecholamine release from an adrenal PCC or extra-adrenal paraganglioma can be difficult to diagnose and may require an unconventional management strategy to achieve good outcomes. We describe a case of PCC crisis presenting with acute respiratory distress syndrome (ARDS) that resolved with stabilization on veno-venous (VV) extracorporeal membrane oxygenation (ECMO) during adrenalectomy. Case Description A 30-year-old man with a history of severe alcohol use disorder and a prior hospital admission for alcohol withdrawal syndrome presented with sudden-onset hemoptysis, altered mental status, and severe dyspnea that rapidly deteriorated to ARDS requiring ECMO support. He demonstrated hemodynamic collapse after cannulation for VV-ECMO and stabilized after conversion to veno-arterial-ECMO, but ARDS persisted and he developed acute renal failure. Computed tomography without contrast done as part of work-up for a presumed infection revealed a 6.9 × 6.4 cm right adrenal mass suspicious for pheochromocytoma. Plasma and random urine metanephrine levels were markedly elevated. ARDS persisted despite α- and β-adrenoreceptor blockade, and he underwent laparoscopic right adrenalectomy with VV-ECMO support. Pathology confirmed PCC with intermediate risk for malignancy. Postoperatively, he was weaned off respiratory and renal support within 10 days, showed rapid clinical improvement, and was discharged 1 month later. Conclusion This case highlights diagnostic and management challenges associated with patients with PCC crisis presenting with ARDS. A multidisciplinary team approach is critical to identifying appropriate treatment strategies.

Introduction Many patients admitted to hospitals with acute trauma have positive serum blood alcohol levels. Published associations between alcohol use, injury patterns, and outcomes are inconsistent. We sought to further delineate the impact of alcohol use and alcohol withdrawal on hospital outcomes amongst acute trauma patients. Methods We performed a retrospective analysis of adult trauma patients hospitalized at a suburban level 1 trauma center between January 2015 and September 2019 with a blood alcohol level measurement and/or classification as alcohol withdrawal syndrome (AWS). Patients were separated into three groups: BAL ≤10 mg/dL, BAL >10 mg/dL, and alcohol withdrawal syndrome (AWS). Results Overall, 3896 patients met study criteria with 75.6% BAL ≤10, 23.2% BAL >10, and 1.2% AWS. The median age was significantly different (BAL ≤ 10: 59 years, BAL > 10: 44 years, AWS: 53.5 years). Alcohol withdrawal was experienced by patients with BAL ≤10 and BAL >10. While injury severity and mortality were similar across all 3 groups, AWS patients experienced significantly longer hospital and ICU lengths of stay, unplanned ICU admission, need for mechanical ventilation, and higher rates of complications. Patients with AWS had high rates of acute neuropsychiatric symptoms, complicating their management. Conclusions Except for mortality, AWS patients experienced worse outcomes. The complex nature of alcohol withdrawal cases, including the possibility of developing AWS despite a negative BAL on admission, emphasizes the need for early assessment for alcohol withdrawal risk factors and input from specialists.

Introduction and Aim: Management strategies of Alcohol Withdrawal Syndrome could be optimized if patients with greater risk are identified early and treated aggressively. Studying the pattern and predictors of alcohol withdrawal syndrome was the main objective of our study. Materials and Methods: A total of 100 consenting male patients in the age group of 18-60 years diagnosed with alcohol dependence and uncomplicated alcohol withdrawal undergoing in-patient detoxification in tertiary care center in north India were included in the study. A semi structured proforma was used to collect socio-demographic data, Alcohol Use Disorders Identification Test (AUDIT) was used as screening tool and Clinical Institute Withdrawal Assessmentfor Alcohol-revised (CIWA- Ar) was used to assess severity of withdrawal. Results: Symptoms like difficulty in orientation, seizures and hallucinations were relatively specific for severe AWS, while tremors and anxiety were common to all the patients and were non-specific for predicting severity of AWS. The severity of AWS symptoms correlated significantly with increasing age, duration of alcohol use and AUDIT score. Conclusion:We concluded that increasing age, longer duration of alcohol use, higher AUDIT score and symptoms related to hallucinations, orientation and seizure are linked to severe alcohol withdrawal. Prior knowledge of these predictors will help to identify the patients at risk of severe alcohol withdrawal so that individual care can be enhanced.

Diazepam is one of the most widely prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS). However, diazepam therapy often turns out to be ineffective, and some patients experience dose-dependent adverse drug reactions. Previous studies have shown that the metabolism of diazepam involves the CYP2C19 isoenzyme, whose activity is highly dependent on polymorphism of the encoding gene. The objective of our study was to investigate the effects of CYP2C19*2 genetic polymorphisms on plasma and saliva concentrations of diazepam as well as its impact on the efficacy and safety rates of therapy in patients with AWS. The study was conducted on 100 Russian male patients with AWS who received diazepam in injections at a dosage of 30.0 mg/day for 5 days. Genotyping was performed by real-time polymerase chain reaction. The efficacy and safety assessment was performed using psychometric scales. We revealed differences in the efficacy and safety of therapy in patients with different CYP2C19 681G>A genotypes. Therapeutic drug monitoring (TDM) revealed the statistically significant differences in the levels of diazepam plasma concentration: (GG) 199.83 [82.92; 250.58] vs (GA+AA) 313.47 [288.99; 468.33], p=0.040, and diazepam saliva concentration: (GG) 2.80 [0.73; 3.80] vs (GA+AA) 5.33 [5.14; 6.00], p=0.003).

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.

Relevance. To relieve alcohol withdrawal syndrome, intravenous infusion of glucose and antidotes to neutralize ketone bodies is used. But after treatment, the craving for alcohol remains, and relapses of alcohol consumption are observed in 60-90% of patients. It remains unclear if there is a connection between hypoglycemia, ketosis, on the one hand, and the craving for alcohol consumption, on the other hand. Objective: to find out the effect of glycemic level normalization and prolonged maintenance of normal blood glucose concentration on ethanol consumption in alcoholized rats. At the same time, we have chosen two alternative ways to eliminate hypoglycemia: 1) by providing animals with unlimited access to a water trough filled with glucose solution; 2) by forced feeding of animals with a high-carbohydrate diet. Materials and methods. 70 rats were housed in the individual cages. First, two water troughs were placed in each cage for one week: the first one was filled with pure water and another one contained 5% glucose solution. Second, forced alcoholization of rats was performed by leaving one trough filled with 10% ethanol solution in each cage. Duration of alcoholization was different: 3 weeks for the 1st group of rats (n=20), 6 weeks for the 2nd group of animals (n=20), and 16 weeks for the 3rd group of rats (n=20). Animals of the control group (n=10) received pure water. Third, after forced alcoholization, animals of the experimental groups had free access to three different troughs for three weeks: the first trough was filled with pure water, the second one – with 5% glucose solution, and the third one contained 10% ethanol solution. Rats of the control group were able to choose between water and 5% glucose solution. At the third stage, animals of the experimental groups were divided into two subgroups with 10 rats in each one. Animals of one of the subgroups from each experimental group were kept on a high-carbohydrate diet: they were administered 1 ml of 40% starch kissel (2.0 g/kg, in terms of glucose) per os 3 times a day. The volumes of all consumed fluids were recorded daily throughout the experiment. The results were processed using the MedStat program. Results. Healthy rats drank 2.5±0.6 ml of water and 1.6±0.6 ml of glucose solution per 100 g of body weight daily. In the first 7 days of forced alcoholization, the animals drank 3.1±0.7 ml of ethanol solution per 100 g of body weight. By the end of the third week, consumption of ethanol solution increased up to 4.9±0.8 ml per 100 g of body weight (p

Investigation of the pathogenesis of alcoholism in humans using different methodological approaches has facilitated detection of important biological factors of consequent metabolic diseases, endocrine disorders, and other medical conditions, such as alcoholic cardiomyopathy, alcoholic hypertension, heart and vascular lesions, alcoholic liver disease, alcoholic pancreatitis, etc. Alcohol abuse leads to damage to the nervous system, which can result in neurological and mental disorders, including alcoholic polyneuropathy, psychosis, and alcohol dementia. The complexity and versatility of the harmful effects of regular alcohol consumption on the human body can be considered in the perspective of a chronobiological approach, because alcohol is chronotoxic to biological processes. As a rhythm regulator, melatonin exerts a wide range of different effects: circadian rhythm regulation, thermoregulation, sleep induction, antioxidant, immunomodulatory, and anti-stress ones. This review presents from a chronobiological perspective the impact of melatonin on alcohol intoxication in terms of mental disorders, sleep and inflammation, hepatic injury, and mitochondrial function. It discusses the main clinical effects of melatonin on alcohol injury and the main targets as a therapy for alcohol disorders. Chronobiological effects of ethanol are related to melatonin suppression that has been associated with, among others, cancer risk. Exogenous melatonin seems to be a promising hepato- and immune-protector due to its antioxidant and anti-inflammatory properties, which in combination with other medicines makes it useful to prevent alcoholic organ damage. The reason for the scientific interest in melatonin as a treatment for alcoholism is obvious; the number of cases of this pathology that gives rise to metabolic syndrome, and its subsequent transformation into steatohepatitis, liver fibrosis, and cirrhosis, is increasing worldwide. Melatonin not only exerts antioxidant effects but it exerts various other effects contributing to the management of liver conditions. This review discusses the interaction between normal and pathological processes caused by alcohol consumption and the relationship between alcohol and melatonin in these conditions.

Objective: To review the literature describing the use of adjunctive phenobarbital in the treatment of severe alcohol withdrawal syndrome (AWS). Data Sources: PubMed and EMBASE were searched using the following terms: phenobarbital, adjunct, refractory or treatment resistant, severe or complicated, and alcohol withdrawal delirium or alcohol withdrawal seizures. Study Selection and Data Extraction: The search was limited to randomized controlled trials (RCTs) and cohort studies published in English. Data Synthesis: Seven studies were identified in the emergency department (ED; RCT, n = 1; cohort, n = 2), general medicine ward (cohort, n = 1), and intensive care unit (ICU; cohort, n = 3) settings. For all studies set in the ED and general medicine ward and for 1 ICU study, phenobarbital plus symptom-guided benzodiazepine therapy was compared to symptom-guided benzodiazepine monotherapy. The other 2 ICU studies examined adjunctive phenobarbital before and after implementation of a protocol, meaning patients in both arms could have received phenobarbital. Overall risk of bias across all studies was low to moderate. Relevance to Patient Care and Clinical Practice: The specific role of adjunctive phenobarbital in AWS is not clear because a majority of studies are retrospective cohorts with varying primary outcomes in different patient care settings. Conclusions: In the ED and general medicine ward, phenobarbital demonstrated benzodiazepine-sparing effects. In the ICU, when a protocol guides phenobarbital use, the need for mechanical ventilation may be reduced. Adjunctive phenobarbital was well tolerated. Because of study limitations, it is challenging to provide specific recommendations for adjunctive phenobarbital use in severe AWS.

Background The Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) is commonly used in hospitals to titrate medications for alcohol withdrawal syndrome (AWS), but may be difficult to apply to intensive care unit (ICU) patients who are too sick or otherwise unable to communicate. Objectives To evaluate the frequency of CIWA-Ar monitoring among ICU patients with AWS and variation in CIWA-Ar monitoring across patient demographic and clinical characteristics. Methods The study included all adults admitted to an ICU in 2017 after treatment for AWS in the Emergency Department of an academic hospital that standardly uses the CIWA-Ar to assess AWS severity and response to treatment. Demographic and clinical data, including Richmond Agitation-Sedation Scale (RASS) assessments (an alternative measure of agitation/sedation), were obtained via chart review. Associations between patient characteristics and CIWA-Ar monitoring were tested using logistic regression. Results After treatment for AWS, only 56% (n = 54/97) of ICU patients were evaluated using the CIWA-Ar; 94% of patients had a documented RASS assessment (n = 91/97). Patients were significantly less likely to receive CIWA-Ar monitoring if they were intubated or identified as Black. Conclusions CIWA-Ar monitoring was used inconsistently in ICU patients with AWS and completed less often in those who were intubated or identified as Black. These hypothesis-generating findings raise questions about the utility of the CIWA-Ar in ICU settings. Future studies should assess alternative measures for titrating AWS medications in the ICU that do not require verbal responses from patients and further explore the association of race with AWS monitoring.

Background: Diazepam is one of the most commonly prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on the efficacy and safety of diazepam therapy. Objective: The objective of our study was to study the effect of CYP3A isoenzymes activity on the efficacy and safety of diazepam in patients with AWS. Methods: The study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg / day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Results: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP3A4 C>T intron 6 ( rs35599367) genotypes: ( CC) −9.0 [−13.0; −5.0], ( CT+TT) −13.5 [−15.0; −10.0], p = 0.014. The scores on the UKU scale, which was used to evaluate the safety of therapy, were also different: ( CC) 7.5 [6.0; 11.0], ( CT+TT) 11.0 [8.0; 12.0], p = 0.003. Conclusion: Possible relationship between the CYP3A activity, evaluated by the content of the urinary endogenous substrate of the given isoenzyme and its metabolite, the 6-beta-hydroxy cortisol (6-β-HC) / cortisol ratio, and the efficacy of diazepam was demonstrated. This possible relationship was also supported by the genotyping results. This should be taken into consideration when prescribing this drug to such patients in order to reduce the risk of pharmacoresistance.

Alcohol use disorder is one of the main causes of morbidity and mortality in the world. Alcoholic liver disease is a common complication of this disorder, and hepatic encephalopathy is a serious complication of alcoholic cirrhosis. Precipitating factors may be related to infection, gastrointestinal bleeding, dehydration or the effects of psychotropic drugs (e.g. benzodiazepines and non-benzodiazepine hypnotics). We present a case of the hospital management of a patient with a severe alcohol use disorder, cirrhosis and hepatic encephalopathy who developed alcohol withdrawal symptoms while in hospital, and discuss the complexity of the antagonistic management of a GABAergic delirium characteristic of hepatic encephalopathy in the context of a glutamatergic-noradrenergic delirium due to alcohol withdrawal.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Aim There are potential clinical, ethical and legal concerns with overdosing benzodiazepines (or barbiturates) for the treatment of moderate to severe alcohol withdrawal symptoms (AWS) through telemedicine or ambulatory outpatients. A rapid systematic review to (a) qualitatively summarize the non-benzodiazepine treatment alternatives, (b) evaluate the quality of evidence for the same to effectively manage moderate to severe AWS. Methods We conducted searches on PubMed (January 1990 to 31 March 2020), Cochrane Central Register of Controlled Trials, and Google Scholar. We selected the English language randomized controlled trials (RCTs) assessing the efficacy and adverse effects of non-benzodiazepine and non-barbiturate medications among adults with a diagnosis of AWS. Data extraction was done in a predefined format. Risk of bias (RoB) assessment and qualitative synthesis of evidence was done with the RoB2 tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) proGDT. Results Thirty-four RCTs were included. Gabapentin (n = 6), carbamazepine (n = 5), baclofen (n = 5), valproate (n = 3), clonidine/lofexidine (n = 3) and acamprosate (n = 2) had more than one trial with a particular comparison group. Four studies were found to have a low ROB. The GRADE evidence summary showed gabapentin had a ‘moderate’ level of evidence against standard benzodiazepine treatments for reducing the severity of AWS. The level of certainty was ‘low’ for carbamazepine, baclofen and valproate and ‘very low’ for acamprosate and clonidine/lofexidine. Reported adverse events between these alternative medications and benzodiazepines or placebo were generally unremarkable. Conclusions Although benzodiazepines remain the treatment of choice for AWS, during particular circumstances, gabapentin could be an alternative although like benzodiazepines is not without risk when used in the community. Future RCTs must aim to improve upon the quality of evidence.

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3- to 4-year recurring cycle of topics. These topics will be presented at the 2020 International Conference. Below is the adult critical care medicine core including complications of chemotherapy, acute-on-chronic liver failure, alcohol withdrawal syndrome, mechanical circulatory support, direct oral anticoagulants, upper gastrointestinal hemorrhage, and vasopressor selection.

Introduction Caring for patients experiencing alcohol withdrawal syndrome can be challenging. Patients 65 and older are at increased risk for alcohol withdrawal syndrome related complications. The higher prevalence of co-morbidities, including cognitive impairment, longer drinking history and greater sensitivity to alcohol withdrawal syndrome treatment are the result of decreased ability of the brain to adapt to stressors such as illness, trauma, or surgery. Delirium tremens Symptoms may appear earlier from the last drink and present with a wide range of symptoms. The most effective interventions require high-quality nursing care delivery to prevent, decrease the severity and shorten the duration of delirium. Nursing implications Strategies that help minimize these challenges starts with obtaining the patient's selfreport of their alcohol use history. Nurses should be diligent in their monitoring for signs of active alcohol withdrawal. Screening and assessment tools such as the Clinical Institute Withdrawal Assessment for Alcohol-Revised should guide pharmacological management. To support nurses in identifying delirium tremens, this manuscript seek to describe the underlying pathophysiology, key assessment components and nursing management of delirium tremens in the older adult.

Alcohol withdrawal syndrome develops in individuals with alcohol dependence who discontinue or reduce alcohol intake after long-term or binge drinking. Withdrawal symptoms usually occur 6–8 hours after the last alcohol consumption and peak between 24–72 hours. Typical manifestations include tremor, nausea, vomiting, insomnia, agitation, and excess sweating. Complicated withdrawal syndrome may manifest with seizures (including cluster seizures), status epilepticus, acute psychosis and delirium, when hallucinations are accompanied by disorientation in time, place and situation. About 10–15% of patients develop complicated withdrawal syndrome. The seizures in alcohol withdrawal syndrome are triggered in the brain stem and have a mechanism other than that of classic epileptic seizures. Benzodiazepines, which are more effective than other classes of anticonvulsants (they primarily reduce the frequency of convulsions in the first two days after alcohol discontinuation and significantly reduce the risk of death), are the gold standard for the treatment of alcohol withdrawal syndrome. The Clinical Institute of Withdrawal Assessment for Alcohol Scale (CIWA-Ar) is a helpful tool for making decisions on treatment initiation or discontinuation. It should be noted that chronic use of benzodiazepines in the secondary prevention of alcohol withdrawal seizures is not recommended due to the addictive potential of these agents and a more severe course of alcohol withdrawal seizures with benzodiazepine co-dependence.

Aim.Based on the application of methods of normoxic therapeutic compression and hyperbaric oxygenation incombination with pharmacotherapy for the relief of cognitive impairment in alcohol withdrawal syndrome (AWS), to evaluate the effectiveness of their use to optimize the treatment process. Methods.160patients with AWS were examined: 62people underwent hyperbaric oxygenation and 56normoxic therapeutic compression sessions along with symptomatic pharmacotherapy, 42with drugs in accordance with medical care protocols. To assess the severity of the manifestations of AWS, the CIWA-A scale was used. Diagnosis and clinical verification of the diagnosis of alcohol dependence was carried out in accordance with the research criteria of the ICD-10 and AUDIT. To study cognitive impairment, the Schulte table technique was used. Results.The use of the method of normoxic therapeutic compression in the complex treatment of AWS increases the mental performance after the first day of therapy by 4.6times, after the third day of therapy, 3.18times, after the seventh day of therapy, 3.25times, compared with drugs. Conclusion.Oxygen therapy methods in combination with pharmacotherapy should be used when stopping cognitive impairment in alcohol withdrawal syndrome, which will increase the effectiveness of treatment and avoid possible cognitive impairment in pharmacotherapy.

Pseudophakic bullous keratopathy and Fuchs' endothelial dystrophy are the two most common causes of corneal edema after cataract surgery. We report a 61-year-old alcoholic male with bilateral corneal edema that improved after his alcohol abstinence. He had uneventful bilateral cataract surgery 3 years ago and blurred vision in both eyes developed for weeks. As he had no history of endothelial dystrophy, the treatment for viral endotheliitis was used initially yet in vain. We asked him to stop alcohol and adjusted his psychiatric drugs, but he lied about stopping drinking. The corneal edema progressed, and finally, he underwent penetrating keratoplasty in his left eye 1 year later. During hospitalization for surgery, alcohol withdrawal syndrome was noted because he could not drink alcohol in our hospital. After he quit drinking for months, corneal edema in the right eye disappeared. Our case highlights that alcoholism can result in corneal edema, and stopping drinking is necessary in these patients.

Objective To evaluate the efficacy and safety of a fixed-dose gabapentin taper protocol for alcohol withdrawal in hospitalized patients. Patients and Methods We retrospectively identified patients admitted to the hospital from January 1, 2016, to April 30, 2018, for alcohol withdrawal syndrome. Based on the treatment that patients received, they were divided into the gabapentin, benzodiazepine, and combination treatment groups. The primary outcome was length of stay, defined as time from admission to either discharge or 36 hours with Clinical Institute Withdrawal Assessment (CIWA) score less than 10. Inverse probability of treatment weight was used to account for differences in baseline characteristics between groups. Results A total of 443 patients met criteria for inclusion (128, 253, and 62 patients in the gabapentin, benzodiazepine, and combination groups, respectively). Baseline characteristics were similar among all groups. The median gabapentin group length of stay was 4.0 hours shorter than the benzodiazepine group (P=.012). Maximum CIWA score was 2.2 points lower in the gabapentin group (P=.003). No statistical differences were noted among safety outcomes, including incidence of seizure, intensive care unit transfer, or delirium tremens. Results were not statistically altered by inverse probability of treatment weight analysis. Conclusion A fixed-dose gabapentin taper protocol appears to be an effective and safe alternative to CIWA-driven benzodiazepines in patients hospitalized with alcohol withdrawal syndrome, though further research is necessary to define the potential subpopulations that benefit most.

Aims We assessed the relationship between specialist and non-specialist admissions for alcohol withdrawal since the introduction of the UK government Health and Social Care Act in 2012. Methods Using publicly available national data sets from 2009 to 2019, we compared the number of alcohol withdrawal admissions and estimated costs in specialist and non-specialist treatment settings. Results A significant negative correlation providing strong evidence of an association was observed between the fall in specialist and rise in non-specialist admissions. Significant cost reductions within specialist services were displaced to non-specialist settings. Conclusions The shift in demand from specialist to non-specialist alcohol admissions due to policy changes in England should be reversed by specialist workforce investment to improve outcomes. In the meantime, non-specialist services and staff must be resourced and equipped to meet the complex needs of these service users.

Surgical treatment of patients with alcohol use disorder can lead to disturbances (withdrawal syndrome, delirium) which require intensive care treatment. In a surgical ward, the diagnosis of an alcohol related disorder is not always simple. Oftentimes patients conceal or trivialize the issue and as a result are admitted to the hospital in a non-abstinent or unstable state. It is risky to assume that patients with alcohol use disorder will successfully be supplied with alcohol in general hospitals. The risk can be reduced through presurgical identification and alcohol withdrawal of such patients. A literature review concludes that there is no secured evidence for the application of alcohol as prophylaxis or therapy of alcohol withdrawal syndrome in a surgical intensive care unit. The use of intravenous and oral alcohol in intensive care is an unnecessary risk to patients. There are more secure alternatives.

Background Benzodiazepine is first-line therapy for alcohol withdrawal syndrome (AWS), and phenobarbital is an alternative therapy. However, its use has not been well validated in the surgical-trauma patient population. Objective To describe the use of fixed-dose phenobarbital monotherapy for the management of patients at risk for AWS in the surgical-trauma intensive care unit. Methods Surgical-trauma critically ill patients who received phenobarbital monotherapy, loading dose followed by a taper regimen, for the management of AWS were included in this evaluation. The effectiveness of phenobarbital monotherapy to treat AWS and prevent development of AWS-related complications were evaluated. Safety end points assessed included significant hypotension, bradycardia, respiratory depression, and need for invasive mechanical ventilation. Results A total of 31 patients received phenobarbital monotherapy; the majority of patients were at moderate risk for developing AWS (n = 20; 65%) versus high risk (n = 11; 35%). None of the patients developed AWS-related complications; all patients were successfully managed for their AWS. Nine patients (29%) received nonbenzodiazepine adjunct therapy for agitation post–phenobarbital initiation. Three patients (10%) experienced hypotension, and 3 (10%) were intubated. None of the patients had clinically significant bradycardia or respiratory depression. Conclusion and Relevance Fixed-dose phenobarbital monotherapy appears to be well tolerated and effective in the management of AWS. Further evaluation is needed to determine the extent of benefit with the use of phenobarbital monotherapy for management of AWS.

Alcohol withdrawal syndrome (AWS) can range from mild jittery movements, nausea, sweating to more severe symptoms such as seizure and death. Severe AWS can worsen cognitive function, increase hospital length of stay, and in-hospital mortality and morbidity. Due to a lack of reliable history of present illness in many patients with neurological injury as well as similarities in clinical presentation of AWS and some commonly encountered neurological syndromes, the true incidence of AWS in neurocritical care patients remains unknown. This review discusses challenges in the assessment and treatment of AWS in patients with neurological injury, including the utility of different scoring systems such as the Clinical Institute Withdrawal Assessment and the Minnesota Detoxification Scale as well as the reliability of admission alcohol levels in predicting AWS. Treatment strategies such as symptom-based versus fixed dose benzodiazepine therapy and alternative agents such as baclofen, carbamazepine, dexmedetomidine, gabapentin, phenobarbital, ketamine, propofol, and valproic acid are also discussed. Finally, a treatment algorithm considering the neurocritical care patient is proposed to help guide therapy in this setting.

Alcohol withdrawal syndrome (AWS) is a serious medical condition of high variability in alcohol use disorder (AUD) after drinking cessation. Identification of clinical biomarkers capable of detecting severe AWS is needed. While alcohol consumption and withdrawal are linked with lipid profile dysregulation, the relationship between lipid levels (high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) and AWS is unknown. Therefore, this study investigated whether HDL-C, LDL-C, and triglycerides conferred risk for moderate-to-severe AWS symptoms in treatment-seeking individuals (n = 732) admitted to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) alcohol treatment program. Lipid levels were measured upon admission, and the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) assessed AWS severity for generating a three-level AWS typology (none-to-mild, moderate, and severe). Multivariable multinomial logistic regression examined whether lipid levels were associated with risk for moderate-to-severe AWS. We found significant predictive relationships between AWS and HDL-C, LDL-C, and triglycerides. While extremely high HDL-C (≥100 mg/dL) conferred the highest odds for moderate (4.405, 95% CI, 2.572–7.546, p < 0.001) and severe AWS (5.494, 95% CI, 3.541–8.523, p < 0.001), the lowest odds ratios for moderate AWS (0.493, 95% CI, 0.248–0.981, p = 0.044) and severe AWS (0.303, 95% CI, 0.223–0.411, p < 0.001) were associated with high LDL-C (≥160 mg/dL). The present study demonstrates that altered lipid levels, measured upon admission for inpatient AUD treatment, may help to predict which individuals are at risk for medically relevant moderate-to-severe AWS. This suggests that further research into the role of lipid biomarkers in AWS may be beneficial for identifying biologically determined risk profiles in AUD.

Thrombocytopenia is a decrease in the platelet count below 150,000 in a microliter of blood, i.e., below the lower limit of the reference range, which is 150,000-400,000/μL. The phenomenon of thrombocytopenia related to heavy drinking began to arouse interest in the 1960s and 1970s. It was initially described in case reports and clinical studies on small groups. In the following years, the phenomenon itself and the significance of alcohol-induced thrombocytopenia was studied. Many methodological difficulties inhibiting objective conclusions from research were encountered. Model pathological mechanisms of alcohol thrombocytopenia and the effects of alcohol on the structure and function of platelets were described. Furthermore, the phenomenon of rapid normalization of the number of platelets in people who stopped drinking was described. Relationships between alcohol use, its intensity and occurrence, and intensity of thrombocytopenia have been demonstrated. Predictive platelet counts for alcohol withdrawal syndrome complications have been proven and calculated. The risk of occurrence of withdrawal seizures or delirium tremens in alcohol withdrawal syndrome increases significantly when the platelet count is less than 119,000/μL. The knowledge of the nature of the phenomenon of alcohol-induced thrombocytopenia in a clinical environment allows decisions that are more rational. The attention of clinicians should be drawn to the importance of results of blood tests routinely collected on admission.

About 50% of persons with an alcohol use disorder may have symptoms of alcohol withdrawal syndrome (AWS) when they reduce or discontinue their alcohol consumption. Protracted alcohol withdrawal (PAW), an underestimated and not yet clearly defined clinical condition that follows the acute stage of AWS, is characterized by the presence of substance-specific signs and symptoms (i.e. anxiety, irritability, mood instability, insomnia, craving) common to acute AWS, but persisting beyond the generally expected acute AWS time frames. Considering that PAW symptoms are mainly related to the neuro-adaptive changes of gamma-aminobutyric acid (GABA) and N-methyl-d-aspartate (NMDA) systems, naltrexone, nalmefene, and disulfiram may not be able to suppress the symptoms of PAW. After treatment of the acute phase of AWS, a more specifically pharmacological therapy able to suppress PAW symptoms could perhaps be used earlier and may be more helpful in preventing the risk of alcohol relapse, which remains higher during the first months of treatment. In light of this, medications acting on GABA and NMDA neurotransmitter systems to counterbalance the up-regulation of NMDA and the down-regulation of GABA could be employed in combination and started as soon as possible.

Aim The aim of this study was to describe the characteristics and the nutritional approaches implemented with patients undergoing alcohol withdrawal. Methods A retrospective analysis of medical records for patients admitted to a tertiary hospital for alcohol withdrawal was completed over a 5-year period 2013–2017. Data on nutrition-related assessment and management were extracted and descriptively analysed. Results A total of 109 medical records were included (M = 73, F = 36), with the mean age of patients 47.3 years (SD ± 11.2, range 22–70). The average length of stay was 3.7 days (SD ± 3.9, range 0.70–27.8). Approaches towards nutritional care emerged from micronutrient assessment and supplementation and/or dietetic consultation. Nutrition-related biochemistry data was available for most patients, notably serum levels of sodium, urea and creatinine (102 patients; 93.5%) and magnesium and phosphate (66 patients, 60.5%). There was evidence of some electrolyte abnormalities on admission to hospital. Eight patients had serum micronutrient status assessed; no patients had serum thiamine levels assessed. Parenteral thiamine was provided to 96 patients (88.0%) for 1.9 days (SD ± 1.1, range 1.0–6.0) with a mean dose of 2458.7 mg (SD ± 1347.6, range 300–6700 mg). Multivitamin supplementation was provided to 24 patients (22.0%). Only 23 patients (21.2%) were seen by a dietician of whom 16 underwent a comprehensive nutritional assessment and 3 were screened using the malnutrition screening tool. Conclusion Inconsistent nutritional assessment and management practices were identified across a diverse population group, whilst nutritional professionals were underutilized. Future research should benchmark current guidelines and multidisciplinary approaches considering the role of nutritional specialists in the team.

The objective of the study:to study certain parameters of the autonomic nervous system (ANS) and cognitive functions in patients with acute alcohol intoxication of different severity degrees.Subjects and methods.312 patients with acute alcohol intoxication and chronic alcohol abuse were enrolled in the study. Manifestations, medical history, the duration of drinking bout, ethanol blood level were assessed. Blood panel included ALT, AST, LDH, and blood levels of free ammonia, lactate, and medium molecules. The subjects were divided into three groups: Group I - 78 patients with severe alcohol intoxication, Group II – 166 patients with moderate alcohol intoxication, and Group III – 68 patients with mild alcohol intoxication. The state of ANS was assessed according to the following indicators: heart rate, systolic and diastolic blood pressure, Kerdo vegetative index, and results of cardiointervalography by R.M. Baevsky (1986). The severity of intellectual impairment was assessed using the ММSE scale for 10 positions, the FAB scale for 6 positions, as well as the Reitan test in seconds on the 1st day.Results.In patients of Group I, the alcohol level was 1.5 and 1.35 times lower versus patients in Groups II and III. All patients with severe intoxication had symptoms of toxic hepatitis, which was manifested by a significant increase in ALT, AST, LDH and bilirubin, exceeding the normal limits by 5.4, 5.4, 1.8, and 1.7 times, respectively. Ammonia blood levels in patients with severe intoxication exceeded the norm by 5.6 times, in patients with moderate severity of intoxication – by 3 times, and even in patients with a mild degree – by 1.5 times. The lactic acid level in patients of Group I was 3.2 times above the norm, in patients of Groups II and III – 2.0 and 1.4 times, respectively. In patients with severe intoxication, there was an increase in blood levels of medium molecules over 0.6 units of optical density which reflected severe endogenous intoxication. Assessment of ANS parameters in patients of three groups revealed development of hypersympathicotonia due to the increased tone of the sympathetic department of ANS in proportion to intoxication severity. Cognitive functions at admission were inhibited in proportion to the severity of the patient's condition. Intelligence level as per MMSE scale: at admission, patients of Groups III and II demonstrated mild and moderate cognitive impairment (25.8 ± 2.1 and 23.31 ± 1.80 points); in Group I, indicators for all items were 1.5 times lower versus Groups II and III. Intelligence as per the FAB scale: in patients with severe intoxication, deviations in conceptualization and dynamic praxis were noted. The Reitan test results were best in patients from Group III. Subsequently, 63 (80.7%) patients with severe alcohol intoxication developed alcoholic delirium.Conclusion.Patients with alcohol intoxication demonstrated a decrease in cognitive functions and impaired intelligence proportional to the severity of intoxication and levels of lactate and free ammonia. Increased tone of the sympathetic division of the ANS is typical of acute alcohol intoxication during drinking bout. Cardiointervalography parameters can be used to assess the severity of alcohol intoxication.

BACKGROUND AND OBJECTIVES Despite the high incidence of alcohol withdrawal syndrome (AWS) in psychiatric inpatients, standardized methods for assessing and treating AWS have been studied only once before in this population. We evaluated a novel AWS assessment and treatment protocol designed for psychiatric inpatients. METHODS This retrospective cohort study evaluated outcomes before and after implementation of the protocol. We collected consecutive data on patients (N = 138) admitted to inpatient psychiatric units at a single center. Participants were patients admitted for nonsubstance-related psychiatric reasons, who were also at risk for developing AWS. Those who developed AWS were treated with either (a) treatment as usual (TAU) or (b) a novel standardized protocol. The primary outcome was duration of benzodiazepine treatment for symptoms of alcohol withdrawal. Secondary outcomes included cumulative benzodiazepine dose administered, treatment duration, and incidence of complications. RESULTS Of 138 participants, 83 received TAU and 55 were assessed and treated with the novel protocol. Median duration of benzodiazepine treatment following protocol implementation was 19.7 hours (interquartile range [IQR], 0-46) prior to implementation (TAU) and 0 hours (IQR, 0-15) following protocol implementation (protocol group) (P

Background Alcohol withdrawal syndrome (AWS) and traumatic brain injury (TBI) present with similar signs and symptoms, yet their treatment strategies differ greatly. AWS treatment includes the Clinical Institute Withdrawal Assessment (CIWA) protocol, which grades withdrawal signs and symptoms. A major purpose of CIWA is to guide the addition and titration of central nervous system (CNS) depressants, most commonly benzodiazepines. Conversely, best practice is to avoid these same CNS depressants in the setting of TBI. Thus, patients with TBI presenting with AWS risk may receive undesirable interventions that could worsen outcome. Objective To describe the relationship of TBI diagnosis with CIWA protocol scores and intervention implementation. Design Retrospective cohort observational study. Setting Single university-based, level one trauma center. Patients Three hundred seventy-five patients with head trauma or AWS classification, identified through the trauma center's trauma registry. Interventions CIWA protocol and related medication use. Main outcome measures Frequency of elevated CIWA score, length of CIWA administration, and medication administration incidence were abstracted from patients' medical records. Results The percentage of elevated CIWA scores increased significantly with TBI severity, from 4.5%(0-60) in the No TBI group, up to 12.5% (0-36) in the Mild TBI group, 27.1% (0-57) in the Moderate TBI group, and 50.0% (14-77) in the Severe TBI group. Nominally, lorazepam use showed a similar pattern of escalation with TBI severity, but it did not reach statistical significance. Haloperidol use did significantly escalate with higher TBI severity. No group differences were observed for total lorazepam equivalents or length on the CIWA protocol. Conclusions TBI diagnosis and higher TBI severity level correlate with higher CIWA scores, but neither increased nor decreased benzodiazepine usage was observed. Antipsychotic use did escalate with TBI diagnosis and severity. The risks versus benefits of minimizing benzodiazepines in patients with TBI who are at risk for AWS warrant future study.

Phenazepam is a benzodiazepine tranquilizer that is widely used in Russia. The drug is metabolized by cytochrome P450 3A (CYP3A) isozymes. Since their substrates have an affinity for P-glycoprotein, the polymorphic variants in the ABCB1 gene may affect the safety of this drug. Objective: to analyze associations between the CYP3A5, CYP2C9, CYP2C19, CYP2D6 and ABCB1 gene polymorphisms and the safety of phenazepam treatment for alcohol withdrawal syndrome (AWS). Patients and methods. The investigation enrolled 102 patients diagnosed with uncomplicated AWS (IDC-10 code F10.30). All the patients were followed up for 6 days within which they took phenazepam. 5-ml venous blood samples were collected from each patient for genotyping. The carriage of CYP3A4*22, CYP3A5*3, CYP2C19*2, CYP2C19*17, CYP2C9*2, ABCB1 3435C>T, 1236C>T, and 2677G>T/A polymorphic variants was determined by a real-time polymerase chain reaction assay. Therapy safety was evaluated using the UKU Side-Effect Rating Scale on day 6. Statistical analysis was carried out with SPSS Statistics 21.0. Haplotype and combinatorial analyses were performed using SNPStats. Results and discussion. The greater subjective severity of adverse reactions (ARs) was shown for the homozygotes of ABCB1 1236C>T CC (odds ratio (OR), 2.154; 95% confidence interval (CI), 1.271–3.650; p=0.014) and ABCB1 2677G>T GG (OR, 2.154; 95% CI, 1.271–3.650; p=0.014). On the contrary, a combinatorial analysis revealed the role of ABCB1 3435C>T, 1236C>T, and 2677G>T polymorphic alleles as predictors for the greater subjective severity of ARs. The following statistically significant polymorphic variant combinations were ABCB1 3435-1236–2677 and T-T-T-CYP3A5*3 isozymes (OR=5.03; 95% CI, 1.65–15.34; p=0.0056); T-T-T-CYP2C9*1 (OR=3.61; 95% CI, 1.31–9.92; p=0.015); T-T-T-CYP2C19*1 (OR=2.52; 95% CI, 1.05–6.08; p=0.042). Attention disorders were also established to be associated with the carriage of T-T-T-CYP2D6*1 (OR=2.58; 95 CI, 1.08–6.13; p=0.035). Conclusion. The carriage of ABCB1 3435-2677-1236 (T-T-T) haplotype is significantly associated with the greater severity of ARs in phenazepam-treated patients with AWS.

Objectives To assess the evidence and discuss the risks and clinical relevance of ketamine for the treatment of various disease states impacting the adult critically ill population. Data sources A literature review was performed using PubMed evaluating primary literature published until August 2018. Study selection Case reports, observational studies (cohort, case-control), and randomized controlled trials involving patients 18 years and older in a nonperioperative setting using either IV or intramuscular ketamine were included for analysis. Uses of ketamine discussed focused on critically ill patients in the ICU and emergency department settings. Data extraction Included studies were evaluated for dosing, outcomes, and adverse effects of ketamine. For each study, the design, population, intervention, investigated outcomes, and results were assessed. Data synthesis The evidence was organized according to use of ketamine, which included pain, sedation, status asthmaticus, alcohol withdrawal syndrome, status epilepticus, and acute behavioral psychologic disturbances. Evaluation of the evidence was based on the included primary literature along with any related guideline recommendations. Conclusions Ketamine has suggested potential benefit in several disease states impacting critically ill patients including pain, alcohol withdrawal syndrome, status epilepticus, and acute agitation. Further supporting evidence is needed to validate its use in the setting of critical illness.

Gamma-hydroxybutyrate (GHB) is a central nervous system depressant primarily used as a recreational drug of abuse, but also for the treatment of narcolepsy with cataplexy in adult patients and as an adjuvant for control of alcohol withdrawal syndrome. The main aim of this review is to summarise updated knowledge about GHB pharmacokinetics and pharmacodynamics, acute poisoning, and clinical features of GHB withdrawal syndrome, its diagnosis and medical treatment. The most common clinical signs and symptoms of acute poisoning include sleepiness to deep coma, bradycardia, hypotension, and respiratory failure. Therapy is essentially supportive and based on continuous monitoring of vital signs. GHB withdrawal syndrome shares patterns with other withdrawal syndromes such as alcohol withdrawal and is sometimes difficult to distinguish, especially if toxicological tests are GHB-negative or cannot be performed. There are no official detoxification protocols for GHB withdrawal syndrome, but its therapy is based on benzodiazepine. When benzodiazepine alone is not effective, it can be combined with barbiturates or antipsychotics. Information about abuse and distribution of GHB and its precursors/analogues among the general population is still limited. Their prompt identification is therefore crucial in conventional and non-conventional biological matrices, the latter in particular, to clarify all the issues around this complex molecule., Gama-hidroksibutirat (GHB) depresiv je središnjega živčanog sustava koji se ponajviše zlorabi kao rekreativna droga, ali se primjenjuje i za liječenje narkolepsije s katapleksijom u odraslih bolesnika te kao pomoćni lijek u kontroli sindroma odvikavanja od alkohola. Ljudi i endogeno proizvode GHB, budući da je on prekursor gama-aminomaslačne kiseline (GABA), jednoga od glavnih neurotransmitera s inhibicijskim učinkom na živčani sustav. GHB ima ulogu neuromodulatora u GABA sustavu i uglavnom djeluje preko GABAB receptora. Za zloporabu se čestu kupuju GBH prekursori/analozi gama-butirolakton (GBL) i 1,4-butanediol (1,4-BD) u obliku otapala namijenjenih legalnoj industrijskoj uporabi. Oni, međutim, nisu endogeni. Glavni je cilj ovoga preglednog rada bio sažeti najnovije spoznaje o farmakokinetici i farmakodinamici GHB-a, akutnom trovanju i o kliničkim značajkama sindroma odvikavanja od GHB-a, njegovoj dijagnozi i liječenju. Akutno je trovanje GHB-om donekle i dijagnostički izazov jer su znakovi i simptomi uobičajeni i za depresive središnjega živčanog sustava. Najčešći su klinički znakovi akutnoga trovanja pospanost (sve do duboke kome), bradikardija i hipotenzija te respiratorno zatajenje. Liječenje je u osnovi potporno, uz stalno praćenje vitalnih znakova. Sindrom odvikavanja od GHB-a dijeli značajke s drugim sindromima odvikavanja (npr. od alkohola ili benzodiazepina). Ponekad ih je vrlo teško razlikovati, ponajviše kada su testovi na GHB negativni ili nije moguće napraviti toksikološku analizu. Ne postoje službeni protokoli za detoksikaciju od GHB-a ili njegovih prekursora/analoga. Liječenje se temelji na primjeni benzodiazepina te, ovisno o težini simptoma, sekundarno barbituratima ili antipsihoticima.

Background: Drug utilization evaluation is an important parameter for the safe, effective and rational use of medications in medical care. Alcoholism results in abundant cases of alcohol withdrawal which can prove to be life-threatening if untreated, lorazepam is a drug of choice for Alcohol Withdrawal Syndrome and requires close monitoring as its over-dosing or under-dosing is common in case of withdrawal. Objective: ensures the safe and rational use of Lorazepam in the management of Alcohol Withdrawal Syndrome. Materials and Method: This prospective, observational study was conducted among alcoholic patients admitted in the KC General Hospital, Karnataka, India. Baseline data for Clinical Institute Withdrawal Assessment for Alcohol revised scale (CIWA-Ar) was collected on the day of admission and the response to lorazepam treatment was recorded using the same with respect to the baseline data every 12th hourly after the initial administration until withdrawn. Results: Statistical analysis for 72 patients was done using ANOVA to calculate the overall progression of the syndrome with treatment. Among 72 patients 94.44% were male and 5.55% were female. The mean age of patients reported with AWS was found to be 44.90 years. A significant CIWA-Ar score reduction was observed with a p-value of