Risk for Delirium Tremens in Patients with Alcohol Withdrawal Syndrome

To determine the characteristics associated with an increased risk for delirium tremens (DT) we performed a case-control study at the detoxification units of two hospitals. Cases met DSM-IV criteria for DT. For each case (n = 15), 3 controls (n = 45) were chosen. Eligibility criteria were applied equally to cases and controls. Cases were more likely than controls to report a prior complicated withdrawal (DT or alcohol withdrawal seizure) (53 vs. 27%, OR 3.1, 95% CI 0.94–10.55), have a systolic blood pressure greater than 145 mm Hg on admission (60 vs. 27%, OR 4.1, 95% CI 1.21–14.06), and have comorbidity scores of at least 1 (60 vs. 18%, OR 6.9, 95% CI 1.92–25.08). Zero cases (0%) and 15 (33%) controls had no prior complicated withdrawals and no adverse clinical features (systolic blood pressure >145 or comorbidity score >1). Compared to this group, the odds of being a case and having both prior complicated withdrawal and at least 1 adverse clinical feature was 44.8 (95% CI 4.36–460). Elevated blood pressure, prior complicated alcohol withdrawal and medical comorbidity, alone and in combination, are associated with an increased risk of delirium tremens.     

Independent clinical correlates of severe alcohol withdrawal

This retrospective cohort study sought to identify clinical variables that independently correlate with severe alcohol withdrawal and to quantify risk in a clinically useful manner. The records of 284 inpatients admitted to an acute detoxification unit at a Veterans Affairs teaching hospital were reviewed. Clinical data were recorded on standardized forms at the time of admission and abstracted by a physician reviewer. Alcohol withdrawal severity was prospectively measured with the revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA‐Ar) scale. Seventy‐one patients (25% of cohort) had severe withdrawal. We identified six independent correlates of severe withdrawal: use of a morning eye‐opener (adjusted odds ratio [OR], 5.6; 95% confidence interval [CI], 1.2–25.9), an initial CIWA‐Ar score ≥ 10 (OR, 5.1; 95% CI, 2.4–10.6), a serum aspartate aminotransferase ≥ 80 U/L (OR, 4.2; 95% CI, 2.0–8.8), past benzo‐diazepine use (OR, 3.6; 95% CI, 1.3–9.9), self‐reported history of “delirium tremens”; (OR, 2.9; 95% CI, 1.3–6.2), and prior participation in two or more alcohol treatment programs (OR, 2.6; 95% CI, 1.3–5.6). Significantly higher risk was observed in subjects with three or more independent correlates. In conclusion, several readily available clinical variables correlate with the occurrence of severe alcohol withdrawal. Ascertainment of these variables early in the course of alcohol withdrawal has the potential to improve triage and treatment decisions.     

Intramuscular/oral lorazepam in acute alcohol withdrawal and incipient delirium tremens

Summary

An open study was carried out in 21 chronic alcoholics with severe withdrawal symptoms and incipient delirium tremens to evaluate the efficacy of adjuvant treatment with intramuscular lorazepam (5?mg). All symptoms subsided within 2 hours after a single injection and remained under control with oral lorazepam (mean daily dose 7?mg). No adverse reactions attributable to lorazepam were observed.     

Influence of DRD2 and ANKK1 polymorphisms on the manifestation of withdrawal syndrome symptoms in alcohol addiction

BackgroundWeinvestigated the relationship between withdrawal syndrome symptoms and dopamine receptor 2 DRD2 gene polymorphisms -141 C I/D (rs1799732) exon 8 G/A (rs6276) and ANKK1 (Ankyrin Repeat and Kinase Domain Containing 1) gene polymorphism Taq 1 A (rs1800497).MaterialA total number of 213 patients who met the ICD 10 criteria for given phenotypes were enrolled in the study. Those phenotypes included: dissocial personality disorder, early onset, alcohol withdrawal syndrome with seizures, alcohol withdrawal syndrome with delirium tremens, and alcohol withdrawal syndrome with seizures and delirium tremens.ResultsOur results show statistically significant associations between SNP in exon 8 A/G in the DRD2 gene and alcohol withdrawal syndrome with seizures, and between SNP in promoter -141 C I/D in the DRD2 gene and early onset of alcohol dependence (AD). The A/A genotype in exon 8 A/G polymorphism seems to be a positive predictive factor for the presence or the lack of seizures in alcohol withdrawal syndrome. The A/G genotype is possibly a protective factor for this AD phenotype.ConclusionsThese results suggest that both investigated DRD2 polymorphisms have an impact onthe AD phenotype. The findings of the presented study reconfirm that dopamine receptor 2 gene polymorphisms are associated with alcohol addiction and alcohol withdrawal syndrome.     

Pharmacotherapeutic management of acute alcohol withdrawal syndrome in critically Ill patients

ABSTRACT

Introduction

Alcohol withdrawal syndrome is a common and life-threatening condition in patients suffering from alcohol use disorder. Treatment of this syndrome is challenging, especially in patients that are critically ill, either because of withdrawal symptoms or underlying conditions. For the treatment, several pharmacological agents exist, such as benzodiazepines, barbiturates, or dexmedetomidine. Nonetheless, as alcohol withdrawal syndromes can occur in every clinical setting, it is necessary to provide a guideline for clinicians confronted with this syndrome in varying clinical contexts.     

Independent Clinical Correlates of Severe Alcohol Withdrawal

This retrospective cohort study sought to identify clinical variables that independently correlate with severe alcohol withdrawal and to quantify risk in a clinically useful manner. The records of 284 inpatients admitted to an acute detoxification unit at a Veterans Affairs teaching hospital were reviewed. Clinical data were recorded on standardized forms at the time of admission and abstracted by a physician reviewer. Alcohol withdrawal severity was prospectively measured with the revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale. Seventy-one patients (25% of cohort) had severe withdrawal. We identified six independent correlates of severe withdrawal: use of a morning eye-opener (adjusted odds ratio [OR], 5.6; 95% confidence interval [CI], 1.2–25.9), an initial CIWA-Ar score q 10 (OR, 5.1; 95% CI, 2.4–10.6), a serum aspartate aminotransferase 80 U/L (OR, 4.2; 95% CI, 2.0–8.8), past benzodiazepine use (OR, 3.6; 95% CI, 1.3–9.9), self-reported history of delirium tremens (OR, 2.9; 95% CI, 1.3–6.2), and prior participation in two or more alcohol treatment programs (OR, 2.6; 95% CI, 1.3–5.6). Significantly higher risk was observed in subjects with three or more independent correlates. In conclusion, several readily available clinical variables correlate with the occurrence of severe alcohol withdrawal. Ascertainment of these variables early in the course of alcohol withdrawal has the potential to improve triage and treatment decisions.     

传统与改良地西泮负荷疗法对酒精戒断性震颤谵妄的疗效比较

目的：探讨改良地西泮负荷疗法对酒精戒断性震颤谵妄的临床疗效。方法：将60例酒精戒断性震颤谵妄患者随机分成地西泮改良负荷疗法组（研究组）和传统地西泮负荷疗法治疗组（对照组），每组各30例。采用酒精戒断综合征评定量表、抑郁自评量表（SDS）、焦虑自评量表（SAS）、临床疗效总评量表（CGI）评定其疗效。结果：研究组戒断综合征评定量表和临床疗效总评量表（CGI）在治疗后第3天、第5天、第7天时的评分显著低于对照组，而且抑郁自评量表（SDS）、焦虑自评量表（SAS）在第5天、第7天的评分也显著低于对照组。结论：地西泮改良负荷疗法治疗酒精戒断性震颤谵妄安全有效。     

Management of Acute Alcohol Withdrawal Syndrome in Critically Ill Patients

Approximately 16–31% of patients in the intensive care unit (ICU) have an alcohol use disorder and are at risk for developing alcohol withdrawal syndrome (AWS). Patients admitted to the ICU with AWS have an increased hospital and ICU length of stay, longer duration of mechanical ventilation, higher costs, and increased mortality compared with those admitted without an alcohol‐related disorder. Despite the high prevalence of AWS among ICU patients, no guidelines for the recognition or management of AWS or delirium tremens in the critically ill currently exist, leading to tremendous variability in clinical practice. Goals of care should include immediate management of dehydration, nutritional deficits, and electrolyte derangements; relief of withdrawal symptoms; prevention of progression of symptoms; and treatment of comorbid illnesses. Symptom‐triggered treatment of AWS with γ‐aminobutyric acid receptor agonists is the cornerstone of therapy. Benzodiazepines (BZDs) are most studied and are often the preferred first‐line agents due to their efficacy and safety profile. However, controversy still exists as to who should receive treatment, how to administer BZDs, and which BZD to use. Although most patients with AWS respond to usual doses of BZDs, ICU clinicians are challenged with managing BZD‐resistant patients. Recent literature has shown that using an early multimodal approach to managing BZD‐resistant patients appears beneficial in rapidly improving symptoms. This review highlights the results of recent promising studies published between 2011 and 2015 evaluating adjunctive therapies for BZD‐resistant alcohol withdrawal such as antiepileptics, baclofen, dexmedetomidine, ethanol, ketamine, phenobarbital, propofol, and ketamine. We provide guidance on the places in therapy for select agents for management of critically ill patients in the presence of AWS.     

Development and implementation of an alcohol withdrawal protocol using a 5-item scale,the Brief Alcohol Withdrawal Scale (BAWS)

Background: The standard of care for management of alcohol withdrawal is symptom-triggered treatment using the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). Many items of this 10-question scale rely on subjective assessments of withdrawal symptoms, making it time-consuming and cumbersome to use. Therefore, there is interest in shorter and more objective methods to assess alcohol withdrawal symptoms. Methods: A 6-item withdrawal scale developed at another institution was piloted. Based on comparison with the CIWA-Ar, this was adapted into a 5-item scale named the Brief Alcohol Withdrawal Scale (BAWS). The BAWS was compared with the CIWA-Ar and a withdrawal protocol utilizing the BAWS was developed. The new protocol was implemented on an inpatient unit dedicated to treating substance withdrawal. Data was collected on the first 3 months of implementation and compared with the 3 months prior to that. Results: A BAWS score of 3 or more predicted CIWA-Ar score ≥8 with a sensitivity of 85.3% and specificity of 65.8%. The demographics of the patients in the 2 time periods were similar: the mean age was 45.9; 70.6% were male; 30.9% received concurrent treatment for opioid withdrawal; and 14.2% were receiving methadone maintenance. During the BAWS phase, patients received significantly less diazepam (mean dose 81.4 vs. 60.3 mg, P < .001). There was no significant difference in length of stay. No patients experienced a seizure, delirium, or required transfer to a higher level of care during any of the 664 admissions in either phase. Conclusions: This simple protocol utilizing a 5-item withdrawal scale performed well in this setting. Its use in other settings, particularly with patients with concurrent medical illnesses or more severe withdrawal, needs to be explored further.     

Orem护理系统理论在脑卒中患者并发酒精戒断综合征的应用

目的 探讨Orem护理系统理论在脑卒中并酒精戒断综合征患者中的应用效果.方法 将50例脑卒中并酒精戒断综合征患者随机分为观察组和对照组,各25例,对照组采取常规的护理干预措施,观察组在此基础上应用Orem护理系统模式进行护理干预:ADL能力评分≤40分者,实施①环境及人身安全护理(如上床栏,必要时使用保护性约束或适当的镇静剂);②加强意识、思维、认知观察;③避免激惹因素.ADL能力评分60 ～41分者,行肢体功能训练指导,坐、卧姿势,进食等的指导,干预三周后比较两组患者的日常生活能力( ADL),并观察两组患者在住院期间护理并发症的发生率.结果 观察组ADL得分高于对照组t=4.254.而误吸、肺部感染、压疮较对照组发生率低,t检验值分别为2.257、2.038,2.085.结论 将Orem护理系统理论应用于脑卒中并酒精戒断综合症患者的护理,可调动患者及家属的积极性,提高患者的生活质量,实现患者的自我护理和康复.     

Severe alcohol withdrawal syndrome: Evolution of care and impact of adjunctive therapy on course and complications of 171 intensive care unit patients

This single site retrospective observational study assessed the evolution of sedation therapy for severe alcohol withdrawal syndrome in the intensive care unit. Patient records for 2 intervals were reviewed: Interval 1, which included 87 intensive care unit patients admitted January 2005 through September 2007, for whom benzodiazedpine monotherapy was utilized; and Interval 2, January 2010 through December 2010, for whom 54 of 84 (64.3%) intensive care unit patients, including all those intubated, received adjunctive agents, including dexmedetomidine or propofol. Clinical management was similar for both intervals, as well as prevalence of alcohol withdrawal syndrome versus total adult hospital admissions and comorbid conditions. Overall, respiratory failure (53 versus 39%), seizures (36 versus 18%), and pneumonia (51 versus 38%) were less frequent during Interval 2 (all p < .05), with lower benzodiazedpine basal dose requirements for those given adjunctive therapy. However, if instances of pneumonia or respiratory failure related to seizures prior to intensive care unit admission are excluded, the prevalence of these complications was similar (p = ns) for Interval 1 and Interval 2. Intensive care unit and hospital length of stay were not altered by adjunctive therapy, which was typically employed for more severely affected patients. High intensity sedation with adjunctive drugs led to few cardiovascular adverse events and may have facilitated management, but did not alter intensive care unit course of severe alcohol withdrawal syndrome.     

Nimodipine in human alcohol withdrawal syndrome — an open study

The aim of this study was to evaluate the efficacy and tolerability of the DHP Ca2+ antagonist nimodipine in human AWS and post-AWS. Ten hospitalized alcoholics of both sexes with a diagnosis of AWS according to the DSM-III criteria were treated for 3 weeks in monotherapy with nimodipine p.o. at flexible daily dosages. Evaluation of AWS symptoms was performed at baseline and after 3, 5, 7, 10, 14 and 21 days. A statistically significant improvement of AWS was seen at evaluation on day 3, particularly in neurovegetative and psychopathological symptoms, and lasted up to the end of the study. The treatment was well tolerated and no side effects were observed or reported. In this pilot, open study nimodipine proved effective in the treatment of mild-to-moderate AWS. If these data are confirmed in a double-blind study nimodipine could be a rational alternative to benzodiazepines in the treatment of AWS.     

Monitoring of direct alcohol markers in alcohol use disorder patients during withdrawal treatment and successive rehabilitation

Direct and indirect biomarkers are widely applied for the determination of alcohol consumption. They help to assess past or present alcohol consumption. Depending on the window of detection and sensitivity of the investigated marker, punctual alcohol consumption may remain undetected. In this study, different sampling strategies for the intermediary long‐term marker phosphatidylethanol (PEth) are evaluated and compared to the determination of the short‐term markers ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine. Samples from 19 patients undergoing alcohol use disorder treatment were collected during the withdrawal treatment and successive rehabilitation (33 ± 26 days (range: 3–74 days)). With liquid chromatography–tandem mass spectrometry (LC–MS/MS) EtG and EtS in urine, PEth in blood, PEth in dried blood spot (DBS) from venous blood, and PEth in DBS from capillary blood were quantified and compared. The use of volumetric capillary DBS, prepared from 20 μL of blood, provided the same results as the use of venous DBS (95% ± 10%, R² 0.9899 for PEth 16:0/18:1). Capillary DBS sampling has the advantage that it can be performed without venipuncture. The use of PEth in DBS proved to prevent post‐sampling degradation, providing a longer detection in comparison to PEth in liquid blood, which only showed 67% ± 24% of the PEth DBS 16:0/18:1 concentration. When compared with EtG and EtS in urine, PEth monitoring proved to be advantageous for the detection of relapse situations, as the accumulation of PEth in blood prolongs the detectability. In conclusion, volumetric capillary DBS sampling for PEth is a simple and useful tool for compliance monitoring, and avoids hematocrit issues.     

普奈洛尔对失眠病人苯二氮类药物撤药症状的影响

目的:观察普奈洛尔对失眠症病人苯二氮(?)类药物撤药症状的作用和撤药成功率的影响。方法:69例因失眠症服用苯二氮(?)类药物且失眠症状消失的病人随机分为2组(普奈洛尔组33例和常规撤药组36例),撤药方法为1 wk减少原剂量的1/4,4 wk停用苯二氮(?)类药物。普奈洛尔组在撤药时加用普奈洛尔30 mg·d~(-1),分3次服用,常规撤药组按规定撤药,为期6 wk,观察撤药症状、脱落率和撤药成功率的差异。结果:普奈洛尔组撤药症状中的静坐不能、心悸和震颤明显少于常规撤药组(P<0.05),其余撤药症状无显著差异(P>0.05)。撤药成功率普奈洛尔组(61%)高于常规撤药组(36%,P<0.05)。结论:普奈洛尔用于苯二氮(?)类药物撤药的失眠症病人可减轻部分撤药症状,并提高撤药成功率。     

A pilot trial of quetiapine for the treatment of patients with delirium

Twenty-two Korean inpatients with delirium were administered prospectively a flexible dose of quetiapine. The delirium rating scale-revised-severity 98 (DRS-R-98) and clinical global impression scale-severity (CGI-s) scores were assessed at the time of pre- and post-treatment. The DRS-R-98 and CGI-s scores were significantly reduced by 57.3% and 55.1%, respectively. Quetiapine was effective and safe for the treatment of patients with delirium, and could be a useful alternative agent to classical antipsychotics in the treatment of delirium.     

Wernicke-Korsakoff syndrome (WKS) in Australia: no room for complacency

Australia has made a substantial contribution to the recognition and treatment of the Wernicke-Korsakoff syndrome (WKS). Much of this occurred over a generation ago, and vigilance in identifying this condition needs to be sustained. More recently, treatment protocols have been developed by the Royal College of Physicians (London). These provide guidelines on when and how to treat both patients at risk and those with acute Wernicke's encephalopathy (WE). It is not known how widespread these recommendations have been applied in Australia. We highlight these current treatment guidelines and illustrate management issues with two case reports. A decline in treatment practices in the United Kingdom prompted the development of these guidelines. Current treatment practices in Australia have not been reported. All alcohol and drug workers need to be reminded regularly of this condition and the need for prompt recognition and treatment.     

Reports of withdrawal syndrome with the use of SSRIs: a case/non-case study in the French Pharmacovigilance database

The SSRIs can be associated with withdrawal reactions and the objective of this study is to test the existence of an association between reports of withdrawal syndromes with the selective serotonin re-uptake inhibitors in the French spontaneous reports database. All reactions are coded according to the WHO ART dictionary. Cases are reports of reactions of interest (withdrawal syndrome). Non-cases are all reports of reactions other than those being studied. We calculated the odds ratio (OR) as the ratio of the odds of the association of reports of withdrawal syndrome with SSRIs in cases and non-cases. SSRIs are clearly associated with a higher risk of withdrawal syndrome (OR: 5.05, 95% CI: 3.81-6.68) and in particular with venlafaxine and paroxetine (OR: 12.16, 95% CI: 6.17-23.35 and OR: 8.47, 95% CI: 5.63-12.65, respectively). The risk of withdrawal reactions appears to be greater with short half-life drugs such as paroxetine and venlafaxine. The precise mechanisms have not been identified.     

Simple method for producing an alcohol withdrawal syndrome in rats.

Rats received intragastric intubations of ethanol at 8 hr intervals for 1, 7, 15 or 30 days. The dosage for each animal was one which produced observable signs of intoxication 1 hr after the intubation. All of the rats in the experimental groups developed a tolerance to ethanol as indicated by the increasing dose required to induce intoxication, but the degree of tolerance was related to the duration of the ethanol administration. During the withdrawal period the incidence of hyperreactivity, convulsive symptoms, and the susceptibility to audiogenic seizures was determined for all 4 groups. Although every experimental animal displayed withdrawal symptoms, the incidence of these symptoms was found to be an increasing, negatively accelerated function of the duration of ethanol exposure. For situations where voluntary consumption of alcohol is not necessary this method is a simple, controlled, reliable, way of inducing ethanol tolerance and physical dependence in rats.     

米氮平对海洛因依赖者脱毒后期稽延性戒断症状的疗效观察

目的观察米氮平片对海洛因依赖者脱毒后期稽延性戒断症状的疗效和不良反应。方法 60例自愿戒毒者脱毒后,由患者自愿选择米氮平片口服治疗,观察其稽延性戒断症状及不良反应,同时设对照组30例,仅作对症治疗。结果在控制稽延性戒断症状方面,米氮平组与对照组相比差异有统计学意义（P〈0.01）;不良反应两组差异无统计学意义（P〉0.05）。结论在应用美沙酮替代递减疗法完成脱毒后,加用米氮平片进行后续的巩固康复治疗,能够有效地控制海洛因依赖者的稽延性戒断症状,且副反应少、安全,值得推广使用。