Sodium Valproate in the Treatment of the Alcohol Withdrawal Syndrome

1980 ◽  
Vol 14 (3) ◽  
pp. 213-215 ◽  
Author(s):  
D. G. Lambie ◽  
R. H. Johnson ◽  
M. E. Vijayasenan ◽  
E. A. Whiteside
Keyword(s):  
Alcohol Dependence ◽  
Sodium Valproate ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Alcohol Withdrawal Syndrome ◽  
The Other ◽  
Withdrawal Symptoms ◽  
Control Group ◽  
Electrolyte Replacement

The value of sodium valproate in the management of patients during withdrawal from alcohol dependence has been assessed. Alcoholic inpatients were randomly allocated to two groups — one treated with sodium valproate and the other acting as a control. All patients received multivitamins and fluid and electrolyte replacement, and some received chlormethiazole or other tranquillisers. Treatment with sodium valproate (1200 mg daily) was continued for one week. The occurence of seizures and other withdrawal symptoms (tremulousness, nausea, sweating, disorientation) were noted daily. Forty-nine episodes of withdrawal have been included in the trial — 22 in the sodium valproate group and 27 in the control group. Five patients, all in the control group, had seizures. Other withdrawal symptoms disappeared more quickly in the sodium valproate group even though fewer patients were receiving chlormethiazole.

scholarly journals Prevention of alcohol withdrawal seizure recurrence and treatment of other alcohol withdrawal symptoms in the emergency department: a rapid review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Justin Jek-Kahn Koh ◽  
Madeline Malczewska ◽  
Mary M. Doyle ◽  
Jessica Moe
Keyword(s):  
Emergency Department ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Observational Studies ◽  
Alcohol Withdrawal Syndrome ◽  
Withdrawal Symptoms ◽  
Rapid Review ◽  
Controlled Trials ◽  
Seizure Recurrence ◽  
Outpatient Settings

Abstract Background Patients who experience harms from alcohol and other substance use often seek care in the emergency department (ED). ED visits related to alcohol withdrawal have increased across the world during the COVID-19 pandemic. ED clinicians are responsible for risk-stratifying patients under time and resource constraints and must reliably identify those who are safe for outpatient management versus those who require more intensive levels of care. Published guidelines for alcohol withdrawal are largely limited to the primary care and outpatient settings, and do not provide specific guidance for ED use. The purpose of this review was to synthesize published evidence on the treatment of alcohol withdrawal syndrome in the ED. Methods We conducted a rapid review by searching MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (1980 to 2020). We searched for grey literature on Google and hand-searched the conference abstracts of relevant addiction medicine and emergency medicine professional associations (2015 to 2020). We included interventional and observational studies that reported outcomes of clinical interventions aimed at treating alcohol withdrawal syndrome in adults in the ED. Results We identified 13 studies that met inclusion criteria for our review (7 randomized controlled trials and 6 observational studies). Most studies were at high/serious risk of bias. We divided studies based on intervention and summarized evidence narratively. Benzodiazepines decrease alcohol withdrawal seizure recurrence and treat other alcohol withdrawal symptoms, but no clear evidence supports the use of one benzodiazepine over another. It is unclear if symptom-triggered benzodiazepine protocols are effective for use in the ED. More evidence is needed to determine if phenobarbital, with or without benzodiazepines, can be used safely and effectively to treat alcohol withdrawal in the ED. Phenytoin does not have evidence of effectiveness at preventing withdrawal seizures in the ED. Conclusions Few studies have evaluated the safety and efficacy of pharmacotherapies for alcohol withdrawal specifically in the ED setting. Benzodiazepines are the most evidence-based treatment for alcohol withdrawal in the ED. Pharmacotherapies that have demonstrated benefit for treatment of alcohol withdrawal in other inpatient and outpatient settings should be evaluated in the ED setting before routine use.

scholarly journals Efficacy of transcutaneous electrical acupoint stimulation combined with diazepam for acute alcohol withdrawal syndrome: A double-blind randomized sham-controlled trial

2020 ◽  
Vol 48 (4) ◽  
pp. 030006052091005
Author(s):  
Yun Song ◽  
Xiaobin Xue ◽  
Haibin Han ◽  
Cuiluan Li ◽  
Jia Jian ◽  
...  
Keyword(s):  
Sleep Quality ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Pittsburgh Sleep Quality Index ◽  
Controlled Trial ◽  
Alcohol Withdrawal Syndrome ◽  
Control Group ◽  
Double Blind ◽  
Improve Sleep Quality ◽  
Acupoint Stimulation

Objective To compare the efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with diazepam against diazepam alone for treatment of acute alcohol withdrawal syndrome (AWS). Methods In this double-blind randomized sham-controlled trial, men with acute AWS were randomly allocated to either a group treated with TEAS combined with diazepam (n = 57) or a control group treated with sham TEAS combined with diazepam (n = 60). Treatment was performed at four acupoints twice a day for 14 days. The Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar), visual analogue scale (VAS), Pittsburgh Sleep Quality Index (PSQI) and modified Epworth Sleepiness Scale (mESS) were used to evaluate treatment efficacy. Results All scores improved significantly in both groups during the trial. CIWA-Ar scores were lower in the TEAS group than in the control group from day 3 until the end of observation. VAS and mESS scores were also lower in the TEAS group than in the control group on day 7. VAS and PSQI scores were lower in the TEAS group on day 14. Conclusion Combining diazepam with TEAS may result in milder AWS symptoms than diazepam alone, improve sleep quality and reduce sleepiness.

scholarly journals Intraoperative Alcohol Withdrawal Syndrome: A Coincidence or Precipitation?

2013 ◽  
Vol 2013 ◽  
pp. 1-3
Author(s):  
Asish Subedi ◽  
Balkrishna Bhattarai
Keyword(s):  
Alcohol Dependence ◽  
Spinal Anesthesia ◽  
Local Anesthetic ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Alcohol Withdrawal Syndrome ◽  
Spinal Block ◽  
Local Anesthetic Toxicity ◽  
Neck Fracture ◽  
Intraoperative Period

As the prevalence of alcohol dependence is approximately half in surgical patients with an alcohol use disorder, anesthetist often encounters such patients in the perioperative settings. Alcohol withdrawal syndrome (AWS) is one of the most feared complications of alcohol dependence and can be fatal if not managed actively. A 61-year-old man, alcoholic with 50 h of abstinence before surgery, received spinal anesthesia for surgery for femoral neck fracture. To facilitate positioning for spinal anesthesia, fascia iliaca compartmental block with 0.25% bupivacaine (30 mL) was administered 30 min prior to spinal block. Later, in the intraoperative period the patient developed AWS; however, the features were similar to that of local anesthetic toxicity. The case was successfully managed with intravenous midazolam, esmolol, and propofol infusion. Due to similarity of clinical features of AWS and mild local anesthetic toxicity, an anesthetist should be in a position to differentiate the condition promptly and manage it aggressively.

scholarly journals Efficacy of Medications Approved for the Treatment of Alcohol Dependence and Alcohol Withdrawal Syndrome in Female Patients: A Descriptive Review

2015 ◽  
Vol 22 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Roberta Agabio ◽  
Pier Paolo Pani ◽  
Antonio Preti ◽  
Gian Luigi Gessa ◽  
Flavia Franconi
Keyword(s):  
Gender Differences ◽  
Alcohol Dependence ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Alcohol Withdrawal Syndrome ◽  
Female Patients ◽  
Evaluation Of Data ◽  
Different Doses

The aim of this study was to evaluate whether the number of women recruited for studies to establish the efficacy of medications approved for treatment of alcohol dependence (AD) and of alcohol withdrawal syndrome (AWS) is sufficient to reveal possible gender differences in the response to these medications and in suggesting the use of different doses in female patients. Our results show that the rates of women recruited for studies evaluating the efficacy of disulfiram (1%), benzodiazepines (3%), and anticonvulsants (13%) were too low to establish possible gender differences. The rates of women recruited for studies evaluating the efficacy of acamprosate (22%), naltrexone (23%), and nalmefene (30%) were higher and allowed evaluation of data obtained for female patients. Women receive medications for treatment of AD and/or AWS for which efficacy has been demonstrated in studies in which men were more largely represented.

scholarly journals Expirience of implementation of personalized clinical decision support system for dosing of bromdihydrochlorphenylbenzodiazepine in patients with alcohol withdraw syndrome based on the pharmacogenomic markers

2020 ◽  
pp. 13-24
Author(s):  
М.С. Застрожин ◽  
А.С. Сорокин ◽  
Т.В. Агибалова ◽  
И.А. Бедина ◽  
Е.А. Гришина ◽  
...  
Keyword(s):  
Decision Support ◽  
Clinical Decision Support ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Alcohol Withdrawal Syndrome ◽  
Clinical Decision ◽  
Main Group ◽  
Control Group ◽  
Psychometric Scales ◽  
The Difference

Введение: Имплементация систем поддержки принятия решений, способных формировать рекомендации по выбору лекарствен- ного средства и его дозы в соответствии с результатами фармакогенетического тестирования, является актуальной задачей, так как решение ее позволит повысить эффективность терапии и снизить риск развития нежелательных лекарственных реакций.Материалы и методы: В исследовании принимал участие 51 пациент (21 - основная группа, получавшая назначения в соответ- ствии с рекомендациями, основанными на результатах фармакогенетического тестирования, а 30 - группа сравнения, получавшая назначения без них) мужского пола с синдромом отмены алкоголя. Для оценки эффективности и безопасности терапии синдрома отмены алкоголя, которую осуществляли с использованием бензодиазепинового транквилизатора феназепама (бромдигидрохлор- фенилбензодиазепина), а также стандартной дезинтоксикационной и витаминотерапии, применялись международные психоме- трические шкалы и шкалы оценки выраженности нежелательных реакций. Определение полиморфизмов генов CYP2D6*4 (1846G>A, rs3892097), CYP2C19*2 (681G>A, rs4244285), CYP2C19*3 (636G>A, rs4986893), CYP2C19*17 (-806C>T, rs12248560), CYP3A5*3 (6986A>G, rs776746) и ABCB1*6 (3435C>T, rs1045642) осуществлялось методом полимеразной цепной реакции в реальном времени с аллель-специфиче- ской гибридизацией. Интерпретацию результатов фармакогенетического тестирования осуществляли с использованием свободно распространяемого программного обеспечения PharmacoGenomeX2 (www.pgx2.com).Результаты: Получены статистически значимые различия в количестве баллов по всем психометрическим шкалам у пациентов основной группы и группы сравнения. Например, по шкале оценки тяжести синдрома отмены алкоголя к 3-му дню исследования количество баллов в основной группе составляло 13,5 [11,2; 16,0], а в группе контроля - 18,0 [17,0; 22,0] (p < 0,001); к 5-му в основ- ной группе - 6,5 [4,2; 8,0], в группе контроля - 15,0 [14,0; 16,0] (p < 0,001). По шкале безопасности UKU также была получена стати- стически значимая разница. К 3-му дню исследования количество баллов по шкале UKU в основной группе составило 6,0 [5,0; 7,0], а в группе контроля - 7,0 [6,0; 8,0] (p = 0,030); к 5-му дню разница возрастала. В основной группе - 5,5 [3,0; 9,0], в группе контроля - 14,0 [12,0; 19,0] (p < 0,001). Группы были репрезентативны (при включении в исследование разница в количестве баллов отсутствовала). Выводы: Персонализация дозы лекарств в соответствии с фармакогенетическими алгоритмами у пациентов с синдромом отмены алкоголя, способна снизить риск развития нежелательных реакций и фармакорезистентности, что позволяет рекомендовать исполь- зование фармакогенетических систем поддержки принятия решений для подбора дозы лекарств. Introduction: Implementation of the clinical decision support systems capable of forming the recommendations on drug and dose selec- tion according to the results of pharmacogenetic testing is an urgent task. Fulfillment of this task will allow increasing the efficacy of ther- apy and decreasing the risk of undesirable side effects.Materials and methods: The study involved 51 patients (21 - the main group receiving appointments in accordance with the recommenda- tions based on the results of pharamogenetic testing, and 30 - the comparison control group receiving appointments without them) male with alcohol withdrawal syndrome. In order to assess the effectiveness and safety of alcohol withdrawal syndrome, which was performed with the benzodiazepine tranquilizer of phenazepam (bromodihydrochlorophenylbenzodiazepine), as well as standard detoxification and vitamin therapy, international psychometric scales and scales of assessment in expressions of adverse reactions. Genotyping Determination of genetic polymorphisms CYP2D6*4 (1846G>A, rs3892097), CYP2C19*2 (681G>A, rs4244285), CYP2C19*3 (636G>A, rs4986893), CYP2C19*17 (-806C>T, rs12248560), CYP3A5*3 (6986A>G, rs776746) and ABCB1*6 (3435C>T, rs1045642) were realized using real-time polymerase chain reaction with allele specific hybridization. Interpretation of the results of pharmacogenetic testing was carried out with the help of free soft- ware PharmacoGenomeX2 (www.pgx2.com)Results: Statistically significant differences in the number of scores for all psychometric scales in the patients of the main group and the comparison group were obtained. For example, on the scale of assessing the severity of alcohol withdrawal syndrome by the 3rd day of the study, the score in the main group was 13.5 [11.2; 16,0], and in the control group - 18,0 [17,0; 22.0] (p <0.001); to the 5th in the main group - 6.5 [4.2; 8.0], in the control group - 15.0 [14.0; 16.0] (p <0.001). On the UKU security scale, a statistically significant difference was also obtained. By the 3rd day of the study, the UKU score in the main group was 6.0 [5.0; 7,0], and in the control group - 7,0 [6,0; 8.0] (p = 0.030); by the 5th day the difference increased. In the main group, 5.5 [3.0; 9.0], in the control group - 14.0 [12.0; 19.0] (p <0.001). The groups were representative (when included in the study, the difference in the number of points was absent).Conclusion: Personalization of the dose of drugs in accordance with pharmacogenetic algorithms in patients with alcohol withdrawal syn- drome, can reduce the risk of unwanted reactions and pharmacoresistance, which allows to recommend the use of pharmacogenetic deci- sion support systems for drug dosage selection.

scholarly journals Dynamics of neurospecific autoimmune disorders and cognitive functions in patients with polytrauma and alcohol withdrawal syndrome complicated by alcohol delirium

2021 ◽  
Vol 25 (4) ◽  
pp. 605-609
Author(s):  
Y. V. Volkova ◽  
S. S. Dubivska ◽  
A. V. Omelchenko-Seliukova ◽  
O. V. Biletskyi
Keyword(s):  
Cognitive Function ◽  
Healthy Volunteers ◽  
Cognitive Functions ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Alcohol Withdrawal Syndrome ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Group 2 ◽  
Group 1

Annotation. Polytrauma is considered the main cause of death among people younger 45 years. Among trauma patiens 15-20% regularly take alcohol, close to 32% of patients who needed intensive therapy to alcohol withdrawal syndrome (AWS), and 5-20% of the progressed to alcohol delirium. The aim of the study is to analyze the dynamics of autoimmune response to markers of neurodestruction in the blood of patients with moderate polytrauma and alcohol withdrawal, complicated by alcohol delirium and assessment of cognitive functions depending on the method of sedation. The study involved 80 patients with moderate polytrauma with alcohol withdrawal, complicated by alcohol delirium. The median age was 45 years (39-54). Patients in Group 1 (n=40) were given dexmedetomidine as a sedation method, and in Group 2 (n=40) diazepam sedation was used according to the symptom-trigger protocol. The content of antibodies to neuron-specific enolase (NSE), myelin basic protein (MBP), total human brain antigen (THBA), S-100 calcium were determined by enzyme-linked immunosorbent assay on days 1, 3, 7 and 14 after alcohol delirium. Assessment of cognitive function was performed (after withdrawal from sedation if present) on days 4 and 14 using the Montreal Cognitive Assessment Scale (MoCa). Mathematical processing of the obtained results was performed in accordance with the generally accepted methods of statistical analysis. The critical value of the significance level (p) was taken as ≤5%. Signs, the distribution of which differed from normal, are presented in the form of Me (median), the confidence interval within the first and third quarters [QI - QIII]. To assess the causal role of various factors in the development of lesions used χ-square with the inclusion of the Yates correction and the odds ratio. In the first 24 hours after the manifestation of AD, the levels of autoantibodies in the two groups of patients did not differ significantly from the level of healthy volunteers. Estimation of the level of antibodies to the S-100B protein showed that in group 1 this indicator increased by a maximum of 24.4% and amounted to 15.8 [14.7 - 17.6], while in the second group increased by 32.6% and became 17.5 [15.3 - 19.7]. From the 7th day, the number of antibodies began to decrease in both groups and was 15.6 [13.6 - 16.8] in group 1 and 16.3 [14.1-19.2] in group 2 on the 7th day, and 14.0 [11.6 - 15.3] and 15.2 [ 13.1 - 18.3], respectively, on the 14th day after hospitalization in ICU. The level of antibodies to NSE was maximum on the 3rd day of the study and was 29.8 [28.4 - 31.8] in patients of group 1, which is higher than the initial level by 26.8%, and in patients of group 2 was 31.6 [29.5 -33.2], which exceeds baseline by 33.9% (p=0.0114 between groups 1 and 2). Subsequently, there was a decrease in the level of antibodies to NSE on the 7th and 14th day after the onset of AD, while maintaining a significant difference between the comparison groups. Antibodies to MBP did not differ between groups up to and including day 3, but were significantly higher than in healthy volunteers. On the 7th day, the level of antibodies to MBP in group 1 was 26.8 [24.4 - 28.8], which corresponded to the values of the control group, and in group 2 was 29.3 [27.7 - 31.5], which is significantly more than the first group (p = 0.0017). In the study on day 14, this trend was maintained: the level of antibodies to OBM among patients in group 2 was 28.6 [27.0 - 30.8], while in group 1 it was 26.2 [23.7 - 28.2]. Antibody levels to THBA on day 3 were significantly higher than baseline and were 30.8 [28.4 - 34.5] in group 1 and 32.7 [30.6 - 36.1] in group 2 (p=0.0056). On day 7 and day 14, the number of antibodies THBA in patients of group 1 did not differ significantly from the control group, while in patients of group 2 they were significantly higher on day 7 - 31.5 [29.4 - 34.9] and normalized on day 14. When analyzing the results of the MoCa test after eliminating the main manifestations of alcohol withdrawal syndrome (4 days after admission to ICU), the number of points in the study groups was significantly lower than the control values: in group 1 1.3 times (p <0.0001), in group 2 – 1.6 times (p<0.0001). The differences between the studied groups of patients are significant (p = 0.000087). Thus, the use of dexmedetomidine for the sedation of patients with hypertension and polytrauma reduces autumnal neurodestruction, which improves the prognosis for the restoration of cognitive function.

Curative effects of Dhatryadi ghrita bioactive extracts on ethanol withdrawal syndrome in Wistar rats

2020 ◽  
Vol 16 ◽  
Author(s):  
Rashmi Saxena Pal ◽  
Amrita Mishra
Keyword(s):  
Locomotor Activity ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Wistar Rats ◽  
Alcohol Withdrawal Syndrome ◽  
Signs And Symptoms ◽  
Normal Diet ◽  
Ethanol Withdrawal ◽  
Control Group ◽  
Alcoholic Extract

Background: Alcohol withdrawal syndrome leads to irritability, aggressiveness, body posture and motor abnormalities, sensory hyper reactivity and changes in various enzyme levels. Dhatryadi ghrita penetrates the blood- brain barrier to decrease the cravings for alcohol in this syndrome. Objective: To evaluate the effect of alcoholic extract of Dhatryadi ghrita on alcohol withdrawal syndrome in Wistar rats. Material & Methods: A liquid diet with 7.2%, v/v ethanol was administered to the Wistar rats for 21 days. Control group animals received saline and normal diet. After alcohol withdrawal, rats were examined at 6th and 24th hour for anxiety and hyper locomotor activity as major withdrawal signs. Anxiety due to ethanol withdrawal was tested with the help of elevated plus maze, light and dark models. The hyper locomotor activity was assessed using Actophotometer. The hepatic enzymes level was determined with the help of the Bio-chemical Analyzer. Ghrita extract (100, 200,300 mg/kg, oral) were administered to different groups and diazepam as standard (2 mg/kg, i.p) were administered to the treatment group animals 30 minutes before alcohol withdrawal estimation. Drug treatment was administered 30 minutes before the second observation at the 24th hour. Results: Findings from the present study revealed that Ghrita extract treatment at doses 100, 200 and 300 mg/kg, oral in ethanol-dependent rats had a significant protective effect on signs and symptoms of ethanol withdrawal in alcohol-dependent rats. Conclusion: Dhatryadi extract acts effectively for the treatment of alcohol abstinence syndrome. The extract treat¬ment has beneficial effects on ethanol withdrawal depressive-like behavior in rats.

Novel Targets Explored in Treatment of Alcohol Dependence induced Withdrawal Syndrome

2020 ◽  
Vol 19 ◽  
Author(s):  
Antra Gupta ◽  
Heena Khan ◽  
Amarjot Kaur ◽  
Thakur Gurjeet Singh
Keyword(s):  
Alcohol Dependence ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Clinical Status ◽  
Alcohol Withdrawal Syndrome ◽  
Therapeutic Interventions ◽  
Clinical Aspects ◽  
Gamma Aminobutyric Acid ◽  
Novel Targets

: Alcohol withdrawal syndrome (AWS) is characterized as termination of chronic and sustained alcohol use that leads to severe symptoms of distress or loss of daily functions when alcohol consumption is diminished or stopped. It is a debilitating manifestation of alcohol dependence and responds poorly to the available clinical therapies. Globally alcohol drinking is continuously increasing all across the world. It causes 3.3 million deaths every year (5.9% of all deaths), and 5.1% of the global burden of disease. Alcohol Withdrawal syndrome led to various changes in brain neurotransmitters sys-tem such as GABA, glutamate, non-epinephrine, serotonin. These symptoms result from imbalance in brain receptor be-tween gamma aminobutyric acid (GABA) and N methyl aspartate (NMDA) that occurs when the consumption of alcohol stops after long use. Studies from various in vivo and in vitro animal models of alcohol withdrawal have been conducted to explore new targets for treatment of alcohol withdrawal syndrome. Advancements in the elucidation of AWS mechanism have revealed a number of key targets that have been hypothesized to modulate clinical status. The present review discusses the pathophysiology, neurobiology and treatment of alcohol withdrawal syndrome and its novel targets like corticotrophin releasing factor, sigma, melanocortin-4 receptors, opioid, potassium channels, ghrelin, and endocannabinoid receptors and gut microbiota. This review discusses about various clinical and pre- clinical aspects related with alcohol dependence. The exploration of novel pharmacological targets may provide effective therapeutic interventions for the management of alcohol withdrawal syndrome.

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