Alcohol withdrawal syndrome: diagnostic and therapeutic methods.

Alcohol withdrawal syndrome (AWS) is a medical emergency, rare in the general population, but very common among alcoholic individuals, which can lead to severe complications when unrecognized or late treated. It represents a clinical condition which can evolve in few hours or days following an abrupt cessation or reduction of alcohol intake and is characterized by hyperactivity of the autonomic nervous system resulting in the development of typical symptoms. According to DSM-5 criteria, the alcohol withdrawal syndrome is defined as such: if patients present at least two of typical signs and symptoms. The Clinical Institute Withdrawal Assessment of Alcohol Scale, revised version (CIWA-Ar), is the tool for assessing the severity of AWS. The support to patient with AWS includes pharmacological intervention as well as general support, restoration of biochemical imbalances and specific therapy. Regarding the pharmacological treatment, benzodiazepines represent the gold standard, in particular long-acting benzodiazepines, administered with a gradual reduction up to cessation.

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

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

Caspase-cleaved keratin-18 fragments increase during alcohol withdrawal and predict liver-related death in patients with alcoholic liver disease.

Noninvasive assessment of disease activity in patients with nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) is still unsettled, but essential for the evaluation of disease progression. We here studied the association of total (M65) and caspase-cleaved (M30) serum keratin-18 fragments (n = 204) with histological parameters (n = 106) in heavy drinkers primarily admitted for alcohol withdrawal before and after alcohol detoxification. An age-, sex-, and fibrosis-stage matched NAFLD cohort (n = 30) was used for comparison. The prognostic value of M30 and M65 levels were assessed in an additional prospectively followed-up cohort of 230 patients with alcoholic cirrhosis (AC) using competing risk analyses. Among the histological parameters, both M30/65 correlated significantly and better than any other serum marker with apoptosis and liver damage, such as ballooning (r = 0.65; P < 0.001), followed by lobular inflammation (0.48; P < 0.001), steatosis (0.46; P < 0.001), but less with fibrosis (0.24; P < 0.001). Area under the receiver operating characteristics curves to detect ballooning, steatosis, or steatohepatitis (SH) were slightly better for M30 (P < 0.005). Optimal M30 cut-off values for mild and severe ballooning were 330 and 420 U/L, and 290 and 330 U/L for SH grades 1 and 2. No significant differences of M30/65 were found between the matched NAFLD and ALD cohort. In contrast to aspartate-amino-transferase and M65, M30 levels increased significantly from 391 to 518 U/L during alcohol detoxification. Moreover, levels of M30 and M65 predicted non-hepatocellular carcinoma liver-related mortality in patients with AC during a mean observation interval of 67.2 months. CONCLUSION: Our data suggest M30 as highly specific marker of liver apoptosis both in ALD and NAFLD. In addition, hepatocellular apoptosis, as determined by M30 levels, occurs during alcohol withdrawal, and survival data point toward a novel underestimated role of apoptosis in patients with ALD. (Hepatology 2017;66:96-107).

[Dexmedetomidine in the treatment of acute alcohol withdrawal delirium]. / Dexmedetomidin in der Therapie des akuten Alkoholentzugsdelirs.

Alcohol withdrawal syndrome has a high clinical prevalence. Severe cases must be treated in an intensive care unit and are associated with a high mortality rate, depending on patient comorbidities. Clinical requirements include sedation, control of vegetative symptoms, treatment of hallucinations and, when necessary, anticonvulsive therapy. Currently, there is no single substance that fulfills these requirements. National and international guidelines recommend a combination of various substances. The central α2-adrenergic receptor agonist clonidine is used as a therapeutic adjuvant. In consideration of its pharmacological characteristics, dexmedetomidine is assumed to be more advantageous compared to clondine. Case studies with dexmedetomidine in alcohol withdrawal syndrome show the safety of its application and a benzodiazepine-sparing effect. Its incorporation in escalating intensive care therapy of severe cases could be appropriate.

[APPLICATION OF DEXMEDETOMIDIN FOR SEDATION OF PATIENTS IN ALCOHOL WITHDRAWAL STATE IN THE ICU].

The efficacy and safety of sedation on 44 patients in alcohol withdrawal state (AWS) for use of intravenous dexmedetomidine infusion. Dexmedetomidine increased the duration of target sedation level to 20%, decreased the duration of excessive/insufficient sedation to 10%, it was associated with AWS symptoms regression, better communication with the patient, reduced consumption of benzodiazepines (BZD) from 40 to 30 mg per day and antypsihotics for control AWS symptoms. The common complications of dexmedetomidine infusion were bradycardia and hypotension. Dexmedetomidine could be an alternative drug for sedation patients with mild or moderate AWS and applied in addition to BZD and antipsyhotics in patients with severe AWS.

[Alcohol withdrawal syndrome showing various progress: A case report].

We experienced a case showing various psychotic symptoms following cessation of alcohol consumption. The symptoms included depressive state, delusion, confusion, psychomotor excitement and delirium, all of which disappeared in about two months. At first, we regarded all the symptoms as alcoholic hallucinosis, by a clinical standpoint, in spite of no auditory hallucination in this case. However, taking the overall clinical course into consideration, withdrawal syndrome could have been affected by some factors. One of the possibilities is that delusion might have been induced by aripiprazole. There still may be some other unknown influential factors on withdrawal, which are indicated by previous papers.

Acute alcohol toxicity and withdrawal in the emergency room and medical admissions unit.

Alcohol-related hospital attendances and admissions continue to escalate despite a fall in alcohol consumption levels in the UK population overall. People with alcohol-related problems pose a significant and often disproportionate burden on acute medical services as their management is often complex and challenging. This article focuses on the management of alcohol intoxication, with particular emphasis on aggressive and possibly violent behaviour; alcohol withdrawal; fitting; and the prevention and treatment of Wernicke's encephalopathy.

From Antiquity to the N-Methyl-D-Aspartate Receptor: A History of Delirium Tremens.

Delirium associated with excessive alcohol consumption has been known since antiquity. This condition became more common as the supply of distilled fermented liquors increased. Delirium, including delirium associated with excessive alcohol consumption, was for many centuries regarded as a form of brain inflammation - "phrenitis" - and was treated with depletion. At the end of the eighteenth century treatment by depletion of alcohol-related delirium began to be replaced by sedation and led to significantly better outcomes. Thomas Sutton established that alcohol-related delirium was a disease sui generis, distinct from phrenitis, and he named it delirium tremens. Because historical accounts of this disease are rare, brief, and not easily accessible, we offer this account of events that culminated in the discovery of the molecular basis of delirium tremens.

Características clínicas y evolutivas de la alucinosis alcohólica. Estudio de seis casos / Clinical and evolutionary characteristics of alcoholic hallucinosis. Study of six cases

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Identification and management of alcohol withdrawal syndrome.

Symptoms of alcohol withdrawal syndrome (AWS) may develop within 6-24 h after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for AWS is with benzodiazepines (BZDs). Among the BZDs, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed-dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as α2-agonists (clonidine and dexmetedomidine) and ß-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptic agents can help control hallucinations. Finally, other medications for the treatment for AWS have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin and topiramate. The usefulness of these agents are discussed.

Comparison of oxidative DNA damage between alcohol-dependent patients with and without delirium tremens.

BACKGROUND: Chronic and excessive alcohol consumption increases oxidative stress. We previously found that levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, are elevated in alcohol-dependent patients without delirium tremens (DTs). The aim of this study was to compare serum 8-OHdG levels between alcohol-dependent patients with and without DTs. METHODS: We recruited 16 alcohol-dependent patients with DTs (DTs group) and 58 patients without DTs (non-DTs group). Alcohol withdrawal severity was evaluated using the Chinese version of the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar-C) every 8 hours. Serum levels of 8-OHdG and other biological indices were assayed at baseline and after 1 week of detoxification. RESULTS: The mean 8-OHdG level in the DTs group was significantly higher than that in the non-DTs group (0.50 vs. 0.34 ng/ml, p < 0.001). A significant correlation was found between the highest CIWA-Ar-C scores and serum 8-OHdG levels (ß = 0.43, p = 0.001) in the non-DTs group, but not in the DTs group (ß = 0.34, p = 0.19). An area under receiver operating characteristic curve of 0.83 suggests that 8-OHdG levels potentially differentiate patients with DTs from those without DTs. After dividing the patients into quartiles by 8-OHdG level, we found that compared to the patients in the third and fourth quartiles, the patients in the highest quartile had an odds ratio of 24.1 (p < 0.001) to have DTs, while those in the second highest quartile had an odds ratio of 3.5 (p = 0.19). Serum 8-OHdG levels did not significantly change after 1 week of detoxification in either group. CONCLUSIONS: Alcohol-dependent patients with DTs have higher serum 8-OHdG levels than those without DTs, suggesting that higher oxidative stress carries a greater risk of the occurrence of DTs.

[Delirium in patients with neurological diseases: diagnosis, management and prognosis]. / Delir in der Neurologie : Diagnose, Behandlung und Prognose.

Delirium is a common acute neuropsychiatric syndrome. It is characterized by concurrent disturbances of consciousness and attention, perception, reasoning, memory, emotionality, the sleep-wake cycle as well as psychomotor symptoms. Delirium caused by alcohol or medication withdrawal is not the subject of the current review. Specific predisposing and precipitating factors have been identified in delirium which converge in a common final pathway of global brain dysfunction. The major predisposing factors are older age, cognitive impairment or dementia, sensory deficits, multimorbidity and polypharmacy. Delirium is always caused by one or more underlying pathologies which need to be identified. In neurology both primary triggers of delirium, such as stroke or epileptic seizures and also secondary triggers, such as metabolic factors or medication side effects play a major role. Nonpharmacological interventions are important in the prevention of delirium and lead to an improvement in prognosis. Delirium is associated with increased mortality and in the long term the development of cognitive deficits and functional impairment.

Symptom profile and outcome of delirium associated with alcohol withdrawal syndrome: a study from India.

AIM: To study the profile of delirium associated with alcohol withdrawal syndrome (AWS) in a developing country in terms of symptomatology, associated risk factors/physical complications, and outcome. METHODOLOGY: Using a prospective design, 112 patients in whom delirium could be attributed to AWS as either the sole or a contributory cause were assessed by Delirium Rating Scale-Revised-98 and the associated etiological factors were assessed by using delirium etiology checklist. FINDINGS: In all patients, delirium was acute in onset and all patients had disturbance of sleep-wake cycle and inattention. Other common symptoms were: disorientation (99.1%), fluctuation in symptoms (97.3%), motor agitation (94.6%), and short-term memory disturbance (92.9%). In terms of delirium etiology checklist etiological categories, besides alcohol withdrawal, the most common factors were metabolic/endocrine abnormalities (76%), followed by organ insufficiency and infection (37% and 35%, respectively). Most patients (67%) improved or recovered completely from delirium during the short stay of 4 days. During the short stay of mean duration of 4 days 13.4% of the patients died during the hospital stay. CONCLUSION: Delirium associated with alcohol withdrawal is characterized by an acute onset of symptoms with high prevalence of disturbance of sleep-wake cycle, inattention, disorientation, fluctuation in symptoms, motor agitation, and disturbance in short-term memory. There are certain differences in the symptom profile of delirium associated with alcohol withdrawal and that associated with medical-surgical causes. About one-sixth of the patients developing delirium due to alcohol withdrawal die during the short hospital stay of 4 days.

Agrypnia excitata.

Agrypnia (from the Greek: to chase sleep) excitata (AE) is a syndrome characterized by loss of sleep and permanent motor and autonomic hyperactivation (excitata). Disruption of the sleep-wake rhythm consists in the disappearance of spindle-delta activities, and the persistence of stage 1 non-rapid eye movement (NREM) sleep. Rapid eye movement (REM) sleep persists but fails to stabilize, appearing in short recurrent episodes, isolated, or mixed with stage 1 NREM sleep. Diurnal and nocturnal motor, autonomic and hormonal overactivity is the second hallmark of AE. Of particular interest is the finding that norepinephrine secretion is extremely elevated at all hours of the day and night whereas the nocturnal melatonin peak is lacking. Oneiric stupor is probably an exclusive sign of AE and consists in the recurrence of stereotyped gestures mimicking simple daily life activities. Agrypnia excitata aptly defines 3 different clinical conditions, fatal familial insomnia (FFI), an autosomal dominant prion disease, Morvan syndrome (MS), an autoimmune encephalitis, and delirium tremens (DT), the alcohol withdrawal syndrome. Agrypnia excitata is due to an intralimbic disconnection releasing the hypothalamus and brainstem reticular formation from cortico-limbic inhibitory control. This pathogenetic mechanism is visceral thalamus degeneration in FI, whereas it may depend on autoantibodies blocking voltage-gated potassium (VGK) channels within the limbic system in MS, and in the sudden changes in gabaergic synapses down-regulated by chronic alcohol abuse within the limbic system in DT.

Alcohol withdrawal syndrome.

In susceptible patients, alcohol withdrawal syndrome (AWS) is often precipitated by other medical or surgical disorders, and AWS can adversely affect the course of these underlying conditions. Although the mortality rate of AWS has decreased over the past few decades, significant risk for morbidity and death remain if management is complicated by a variety of conditions. This review of AWS focuses on the scope of the clinical problem, historical features, pathophysiology, clinical presentation, and approaches to therapy, with particular emphasis on severe AWS that requires management in the intensive care unit.

Evolution of Wernicke-Korsakoff syndrome in self-neglecting alcoholics: preliminary results of relation with Wernicke-delirium and diabetes mellitus.

We present a descriptive, retrospective study of initial symptoms, comorbidity, and alcohol withdrawal in 73 alcoholic patients with subsequent Korsakoff syndrome. In 25/73 (35%) of the patients the classic triad of Wernicke's encephalopathy with ocular symptoms, ataxia and confusion, was found. In at least 6/35 (17%) of the initial deliria (95% confidence interval: 10-25%) we observed no other underlying causes, thus excluding other somatic causes, medication, (recent) alcohol withdrawal, or intoxication. We suggest that these deliria may have been representing Wernicke's encephalopathy. A high frequency (15%) of diabetics may reflect a contributing factor of diabetes mellitus in the evolution of the Wernicke-Korsakoff syndrome.

Assessment of characteristics of patient with delirium tremens.

Delirium tremens is the severe form of alcohol withdrawal. It carries a certain degree of mortality and there has been and advancement in the understanding of pathophysiology and risk factors for the development of the condition. This prospective study is carried out to study the characteristic of the patient of delirium tremens in our setting using ICD-10 diagnostic criteria. Thirty seven cases of delirium tremens with majority of males and of all hill origin people were identified. Patients with delirium tremens has been using alcohol for average of 24.8 years with an average intake of around 2.2 litres per day. Most of the patient has seizure and similar episodes in past and using alcohol from morning time.