Course Of Alcohol Withdrawal Research Articles

Alcohol Withdrawal Induced Malignant Catatonia and Response to Bromocriptine: Case Report

Catatonia and malignant catatonia may result in devastating and life-threatening complications like pulmonary embolisms, pneumonia, deep venous thrombosis, rhabdomyolysis, and even death. There have been documented cases implicating alcohol withdrawal as a significant culprit in catatonia. Here, we provide a unique case report of a patient with a complicated medical course, who subsequently developed malignant catatonia secondary to severe alcohol withdrawal, and was successfully treated using both first line treatment of catatonia (lorazepam), and second-line treatment (bromocriptine). Mr. KR is a 32 year-old male with a psychiatric history significant for severe alcohol use disorder, developed fevers, rigidity and dysarthria throughout his admission despite a full negative infectious workup. He was intubated twice, he received his first doses of bromocriptine 2.5mg BID on day 29 of hospitalization. On day 30, he was extubated, and by day 31 he was afebrile, his rigidity and dysarthria had subsided, and he was able to converse coherently. Further titration of bromocriptine (up to 2.5mg every six hours on days 33-37) showed continued improvement, and the patient was eventually transferred out of the ICU. On day 37, a bromocriptine wean was initiated, which KR tolerated and showed continued improvement with return of some baseline activities and resolution of dysarthria. This case report demonstrates the need for increased suspicion for alcohol withdrawal catatonia in patients with a complicated course of alcohol withdrawal, and illustrates a previously undocumented etiology for malignant catatonia.

Assessment and Treatment of Alcohol Withdrawal Syndrome

Alcohol withdrawal syndrome (AWS) is the most common and well-known condition occurring after intentional or unintentional cessation or decreasing heavy drinking. Approximately 5-10% of these people are suffering from serious medical and psychiatric problems, withdrawal seizures, perceptual disturbances, and delirium tremens. Despite acute medical conditions with the high mortality of severe AWS, proper management could decrease the severity and mortality of AWS. The Clinical Institute withdrawal assessment for alcohol-revised version is a valid, reliable, and sensitive instrument for assessing the clinical course and the treatment monitoring of alcohol withdrawal. Benzodiazepine is the pharmacotherapy of choice for alcohol withdrawal. Diazepam or lorazepam treatment is best initiated early in the course of alcohol withdrawal to prevent progression to more severe withdrawal. There are three strategies for the pharmacotherapy of AWS. After the treatment of AWS, most patients should be managed or treated by the continuing care, including the psychosocial treatments, community-based management, and programs for preventing recurrence of AWS.

Alcohol withdrawal hallucinations in the general population, an epidemiological study

Hallucinations are sometimes encountered in the course of alcohol withdrawal; however, both the factors predisposing to alcohol withdrawal hallucinations (AWH) and the implications of AWH with respect to the mechanisms of hallucinations remain unclear. To clarify these issues, we used data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to investigate the demographic correlates, alcohol-use clinical patterns, and psychiatric comorbidities in two groups: drinkers with and without a history of AWH. We estimated the odds ratios for studied factors and used logistic regression analyses to compare the two groups. We found that over 2% of drinkers reported AWH (758 of a sample of 34,533 subjects). Alcohol tolerance and withdrawal seizures were highly associated with AWH, and exposure to alcohol during brain development was associated with a 10-fold increase in AWH compared to exposure during adulthood. African Americans, Native Americans, and unmarried subjects, as well as subjects with lower levels of education and lower levels of income were more likely to experience AWH. Furthermore, those with a history of AWH had higher odds ratios for most psychiatric illnesses than those without such history—yet of anxiety disorders, only panic was associated with AWH. These associations suggest that higher levels of education and of standard of living could protect against AWH; while social isolation, hypervigilance, exposure to alcohol during brain development, and long and severe exposure to alcohol could predispose to AWH.

A Study of Patterns of Platelet Counts in Alcohol Withdrawal.

Aims:This study aimed to evaluate the patterns of platelet counts during the course of alcohol withdrawal and its relationship if any with liver enzymes.Methodology:Forty consecutive patients, with alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-fourth edition, Text Revision criteria, willing for a 10-day inpatient detoxification program and presenting within 12 h of the last consumption of alcohol were recruited in the study. Details about the diagnosis and alcohol consumption patterns were assessed with a detailed psychiatric interview. After admission, routine investigations (complete blood counts [CBCs] and liver function tests) were sent and records were kept. CBC was sent for platelet counts on the 2nd, 4th, 6th, 8th, and the 10th day of alcohol withdrawal.Results:Nearly 40% of the patients developed delirium tremens (DT group) and rest had an uncomplicated alcohol withdrawal (ND group). Platelet counts at baseline and all the 4 days of collection were significantly lower in DT group than the ND group. Platelet counts increased gradually from baseline till 10th day of alcohol withdrawal, mean increase in platelet counts being 88.61 ± 11.60% (median: 61.11%, range [23.41–391.23%]). Platelet counts in 63% of the patients showed a drop on the 4th day of withdrawal before rising till the 10th day of alcohol withdrawal. Platelet counts were not affected by liver enzymes or other alcohol consumption patterns.Conclusions:Transient thrombocytopenia and reverse thrombocytosis during alcohol withdrawal are associated with an initial drop in platelet counts. The synchrony between the drop and the onset of DT needs to be evaluated.

Altered voltage-gated calcium channels in rat inferior colliculus neurons contribute to alcohol withdrawal seizures

We have previously reported that enhanced susceptibility to alcohol withdrawal seizures (AWS) parallels the enhancement of the current density of high-threshold voltage-gated Ca2+ (CaV) channels in rat inferior colliculus (IC) neurons. However, whether this increased current density is a cause or consequence of AWS is unclear. Here, I report changes in the current density of CaV channels in IC neurons during the course of alcohol withdrawal and the potential anticonvulsant effect of intra-IC infusions of L- and P-type CaV channel antagonists. Whole-cell currents were activated by depolarizing pulses using barium as the charge carrier. Currents and seizure susceptibility were evaluated in control animals 3h after alcohol intoxication, as well as 3h (before AWS), 24h (when AWS susceptibility is maximal), and 48h (when AWS susceptibility is no longer present) after alcohol withdrawal. Nifedipine, nimodipine (L-type antagonists) or ω-agatoxin TK (P-type antagonist) were infused intra-IC to probe the role of CaV channels in the pathogenesis of AWS. CaV current density and conductance in IC neurons were significantly increased 3 and 24h after alcohol withdrawal compared with the control group or the group tested 3h following ethanol intoxication. Blockade of L-type CaV channels within the IC completely suppressed AWS, and inhibition of P-type channels reduced AWS severity. These findings suggest that the enhancement of CaV currents in IC neurons occurs prior to AWS onset and that alterations in L- and P-type CaV channels in these neurons may underlie the pathogenesis of AWS.

The toxicologist and delirium: flumazenil as a diagnostic and therapeutic tool for delirium during the course of alcohol withdrawal.

We appreciate the thoughtful comments from Dr Lucyk et al. and the opportunity to clarify and report further details regarding our experience with managing delirium during the course of alcohol withdrawal (AWS). We agree that the treatment of AWS is best managed with symptom-triggered therapy with benzodiazepines, and this is our practice. However, we do not believe that this approach can always limit the occurrence of benzodiazepine-induced delirium, as was demonstrated in our results [1]. In addition, this was not a study of the optimal therapy of alcohol withdrawal, but rather a study of the utility and safety of flumazenil in the delirious patient who has received large doses of benzodiazepines. Flumazenil can improve mental status for patients with hepatic encephalopathy. However, hepatic encephalopathy was highly unlikely as a confounding factor, except possibly in a very few patients. Of the 85 subjects, 45 (53 %) had ammonia levels evaluated during their hospitalization (mean 37, median 33, and range 13–92 mcg/dl). Only 3 of our 85 patients had a clinical diagnosis of hepatic encephalopathy (ammonia levels 43, 64, and 94 mcg/dl). Another four had cirrhosis, but with no evidence of hepatic encephalopathy (ammonia levels 21, 44, 52, 65 mcg/dl). Another patient without change in delirium after flumazenil had Wernicke’s encephalopathy. While alanine transaminase and aspartate transaminase are markers of hepatic inflammation rather than failure, we had transaminase data for every patient, with mean (range) as 66 (10–245 U/L) and 113 (15–665 U/L), respectively. Respectfully, we disagree that paradoxical reactions to benzodiazepines are rare or that “ICU delirium” or persistent AWS were the more likely cause of delirium. Benzodiazepine use, as in our cases, may increase the risk of delirium [2–4]. The fact that 73 % of our total patients improved with flumazenil, most of whom (69 %) had agitated delirium or mixed sedation and agitation, further demonstrates that paradoxical benzodiazepine delirium is not a rare event. ICU delirium is multifactorial and usually has a specific cause such as hypoxia, oversedation or other iatrogenic adverse drug reactions, sepsis, and toxic and metabolic encephalopathies [5]. Regarding AWS, it ordinarily was resolving by the time we gave flumazenil in our cases and was the most common differential diagnosis as the reason to utilize flumazenil. Furthermore, delirium associated with AWS would be unusual to persist beyond 4–5 days of abstinence [6–8], which our data supports. Prolonged AWS was ruled out in the majority of our patients by their improvement with flumazenil in the majority of patients (73 % objective improvement). To further demonstrate that benzodiazepine delirium was the diagnosis in the majority of cases, an average of 8 doses of flumazenil was used with success in the 56 patients who required repetitive dosing. In the other cases, it was useful to exclude benzodiazepine delirium as the etiology. Despite the retrospective and subjective nature of our latest study, the patients were observed at least for the initial flumazenil dose by experienced medical toxicologists, and the result in most cases was unequivocal. Our data could significantly impact the diagnosis and management of patients with delirium during the course of AWS, offering providers an additional diagnostic and therapeutic tool. Further study of the length of stay and costs associated with flumazenil vs placebo (or other therapy) during the course of AWS would be helpful because this could significantly impact patient care and may increase our role as toxicologists in patient care nationwide.

Risk Assessment of Moderate to Severe Alcohol Withdrawal--Predictors for Seizures and Delirium Tremens in the Course of Withdrawal

To develop a prediction model for withdrawal seizures (WS) and delirium tremens (DT) during moderate to severe alcohol withdrawal syndrome (AWS) in a large cohort of inpatients treated for AWS (n = 827). Re-analysis of a cohort study population treated between 2000 and 2009. All patients received a score-guided and symptom-triggered therapy for AWS. Multivariable binary logistic regression models with stepwise variable selection procedures were conducted providing odds ratio (OR) estimates. In the multivariable regression, significant predictors of WS during AWS therapy were a delayed climax of withdrawal severity since admission [OR/10 h: 1.23; 95% confidence interval (CI): 1.1-1.4; P < 0.001)], prevalence of structural brain lesions in the patient's history (OR 6.5; 95% CI: 3.0-14.1; P < 0.001) and WS as the cause of admittance (OR 2.6; 95% CI: 1.4-4.8; P = 0.002). Significant predictors at admission for the occurrence of DT were lower serum potassium (OR/1 mmol/l 0.33; 95% CI: 0.17-0.65; P = 0.001), a lower platelet count (OR/100.000 0.42; 95% CI: 0.26-0.69; P = 0.001) and prevalence of structural brain lesions (OR 5.8; 95% CI: 2.6-12.9; P < 0.001). In this large retrospective cohort, some easily determinable parameters at admission may be useful to predict a complicated course of alcohol withdrawal regarding the occurrence of WS or DT. Using the provided nomograms, clinicians can estimate the percentage likelihood of patients to develop either WS or DT during their course of withdrawal. Prevalence of structural brain lesions in the patient's history does strongly warrant a careful observation of patients.

Elevated adiponectin serum levels in patients with chronic alcohol abuse rapidly decline during alcohol withdrawal

Adiponectin is a circulating protein with hepatoprotective effects. To study the relationship of excessive alcohol consumption and serum adiponectin levels (SAL). The SAL were determined in (i) heavy drinkers without advanced liver damage during the course of alcohol withdrawal, (ii) patients with chronic hepatitis C virus (HCV) infection, (iii) patients with alcohol-associated cirrhosis, and (iv) healthy volunteers that consumed excessive amounts of alcohol for only a short period of time. Further, primary human hepatocytes (PHH) and adipocytes were incubated in vitro with alcohol or serum of patients. Patients with chronic alcohol consumption had significantly higher SAL than HCV-patients with comparable degrees of liver damage. In alcoholics, but not in HCV patients, SAL positively correlated with serum levels of aminotransferases. Further, SAL correlated with the amount of alcohol consumption but declined during the course of alcohol abstinence. After short-term excessive alcohol consumption SAL were not elevated in healthy individuals. Adiponectin mRNA was detectable in adipocytes but not in hepatocytes, and alcohol failed to induce adiponectin in both cell types. In contrast, serum of active drinkers induced adiponectin expression in adipocytes while serum from the same individuals collected after alcohol withdrawal had no effect. Alcohol exhibits a specific effect on SAL that is dose and time dependent, and correlates with the degree of hepatic damage. Alcohol does not seem to affect adiponectin expression directly in adipocytes but potentially via mediators systemically released as a result of the chronic alcohol intake.

Glutamate Decarboxylase Genes and Alcoholism in Han Taiwanese Men

Glutamate decarboxylase (GAD), the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), may be involved in the development of alcoholism. This study examined the possible roles of the genes that code for 2 forms of GAD (GAD1 and GAD2) in the development of alcoholism. An association study was conducted among 140 male alcoholic subjects meeting the DSM-III-R criteria for alcohol dependence and 146 controls recruited from the Han Taiwanese in community and clinical settings. Psychiatric assessment of drinking conditions was conducted using a Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry. The SHEsis and Haploview programs were used in statistical analyses. Nine single-nucleotide polymorphisms (SNPs) at the GAD1 gene were valid for further statistics. Between alcoholic subjects and controls, significant differences were found in genotype distributions of SNP1 (p=0.000), SNP2 (p=0.015), SNP4 (p=0.015), SNP5 (p=0.031), SNP6 (p=0.012), and SNP8 (p=0.004) and in allele distributions of SNP1 (p=0.001), SNP2 (p=0.009), and SNP8 (p=0.009). Permutation tests of SNP1, SNP2, and SNP8 demonstrated significant differences in allele frequencies but not in 2 major haplotype blocks. Three valid SNPs at the GAD2 gene demonstrated no associations with alcoholism. Further permutation tests in the only 1 haplotype block or individual SNPs demonstrated no significant differences. This is the first report indicating a possible significant role of the GAD1 gene in the development of alcohol dependence and/or the course of alcohol withdrawal and outcome of alcoholism.

PROPOSAL OF A COMPREHENSIVE CLINICAL TYPOLOGY OF ALCOHOL WITHDRAWAL—A CLUSTER ANALYSIS APPROACH

To characterize the various courses of alcohol withdrawal. The Alcohol Withdrawal Scale (AWS) was applied to 217 alcohol-dependent patients every 4 h till the symptoms of withdrawal had passed (until each of four consecutive scores were <3). Patients were medicated by a standardized treatment scheme according to AWS-scores. Hierarchical cluster analysis and discriminant analysis were applied. We found five clusters representing increasing severity of alcohol withdrawal. Each cluster is characterized by a combination of the two maximum subscores (vegetative and psychopathological subscore) and three additional psychopathological symptoms (anxiety, disorientation, and hallucination). In 18.4% of the patients, relevant symptoms were not observed (cluster 1), 18.9% developed mild or moderate vegetative symptoms only (cluster 2), and 40.6% additional anxiety (cluster 3). In cluster 4 (11.1%) the most frequent psychopathological symptoms were disorientation and anxiety but no hallucinations, which could be observed only in cluster 5 (11.1%). Discriminant analysis using the maximum subscores at the first day of treatment as independent variables correctly predicted 89.9% of the five clusters. Our findings support a model of alcohol withdrawal clustering along the two dimensions of vegetative and psychopathological severity. Furthermore, the AWS may be useful to predict the course of alcohol withdrawal already at the first day of treatment.

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.

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 > or =10 (OR, 5.1; 95% CI, 2.4-10.6), a serum aspartate aminotransferase > or =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.

Gender and Outpatient Detoxification from Alcohol

Based on gender, we compared demographics, clinical characteristics, and completion rates for outpatient detoxification from alcohol, using oxazepam in conjunction with an intensive day treatment program. Among 64 consecutive patients, nearly half were female. Women were significantly more likely than men to be Medicaid recipients, to have received past mental health treatment, and to have used illicit substances in the four weeks prior to detoxification. Despite these added risk factors, there were no clinical differences noted between men and women in terms of severity of alcohol withdrawal, completion rates for outpatient detoxification, length of detoxification in days, total oxazepam dose in mg/kg, or transition to continued substance abuse treatment. Overall, 89% of patients completed detoxification. These findings suggest that the clinical course of alcohol withdrawal is similar between women and men, and that women can achieve high rates of completion with outpatient detoxification when administer...

Age-related differences in the course of alcohol withdrawal in hospitalized patients.

The aim of this study was to compare the course of alcohol withdrawal (AW) syndromes in different age groups of hospitalized patients. Medical records of 892 patients treated for AW in Nowowiejski Hospital in Warsaw, Poland from 1973 to 1987 were reviewed using a structured questionnaire; a further 321 patients were observed on a prospective basis in the years 1990-1999. We compared severity of the symptoms and the course of AW episodes in five age groups: <30, 30-39, 40-49, 50-59 and > or =60 years old. Although the age groups did not differ in respect of gender, there were significant differences in other demographic variables, such as marital status, education, employment and number of households. We found a greater prevalence of somatic diseases and hypokalaemia in the older age groups. Older patients were hospitalized longer than the younger patients. The amount of alcohol consumed was significantly smaller in the older patients. No significant differences were found between age groups in the duration and severity of AW symptoms. All age groups required comparable doses of medication. The relationship between the duration of AW and the amount of alcohol consumed during the last drinking bout was significant in patients aged >50 years. There was also a significant positive correlation between the occurrence of withdrawal seizures or the severity of AW symptoms and the number of previous AW episodes in patients aged > or =40 years. Although the results did not confirm some previously reported differences in the course of AW between older and younger patients, they point to some new important differences in the conditions and course of AW in the elderly.

Diagnostic and prognostic value of additional neurologic diagnosis in alcohol withdrawal delirium

A severe course of alcohol withdrawal has been observed in 28% of patients in a neurological intensive care unit due to complicating central nerve system (CNS) diseases. In any atypical alcoholic delirium, especially with focal neurological signs, partial seizures, or decreased level of consciousness, CNS diseases like meningoencephalitis, intracranial hemorrhage, or central pontine myelinolysis must be diagnosed by computed tomography (CT) scan and cerebral spinal fluid (CSF) tap. The diagnostic and prognostic value of CT scan and CSF analysis was examined in 32 persons with alcohol withdrawal syndrome or delirium tremens. Neurological complications and cerebral convulsions at the beginning of delirium tremens appear to predispose the patient to a protracted clinical course and necessary mechanical ventilation. Blood-CSF barrier permeability is increased in 70% of alcohol withdrawal patients and that also seems to be a marker of a prolonged clinical course. Cerebral atrophy as shown in CT scan does not play a role in predicting clinical course. In our experience, CT examination or lumbar puncture is not necessarily recommended if clinical signs are typical for alcohol delirium.

Assessment of the Role of Kindling in the Pathogenesis of Alcohol Withdrawal Seizures and Delirium Tremens

The aim of this study was to evaluate the hypothetical role of kindling phenomenon in the development and course of alcohol withdrawal (AW) seizures and delirium tremens (DT). The 2186 medical records of 1179 patients hospitalized in Nowowiejski Hospital in Warsaw from 1973 to 1987 were reviewed using a structured questionnaire. Investigating the role of kindling, a course of consecutive AW episodes of patients hospitalized several times was analyzed. The relationships of withdrawal seizures with the duration of alcohol abuse, the number of prior detoxification episodes, and other variables were also studied. Increasing severity of AW symptoms was observed during the course of consecutive episodes in 22.5% of patients. The first episode of DT was preceded by withdrawal seizures in 11% of cases. First-ever withdrawal seizures occurred more frequently in patients with head injury in the past and with coexisting symptoms of alcohol liver disease. Occurrence of withdrawal seizures and DTs did not correlate with the number of previous withdrawal episodes or with the length of period of intensive drinking. We concluded that the kindling model could be applied only to some cases in the development of AW seizures and DTs. Kindling should be considered as one of the multiple mechanisms involved in the pathogenesis of AW delirium.

Differences in the Course of Alcohol Withdrawal in Women and Men: A Polish Sample

A retrospective study compared the course of alcohol withdrawal, including delirium tremens, in women and men hospitalized in the Nowowiejski Hospital in Warsaw from 1973 to 1987. Medical records pertaining to 1179 patients were analyzed; 13.8% of these patients were women and 86.2% were men. The study showed that women began intensive alcohol drinking later than men (p < 0.0001), but the period between the onset of alcohol abuse and the first occurrence of alcohol withdrawal was shorter in women than in men (p < 0.0001). In the period of heavy drinking before hospitalization, women consumed significantly less alcohol then men (p < 0.0001); moreover, women drank nonbeverage alcohol less frequently than men (p < 0.05). Women were hospitalized substantially longer than men (p < 0.0001), whereas the duration of alcohol withdrawal symptoms at the time of hospitalization was comparable in both groups. Withdrawal seizures were significantly more frequent among men than among women (p < 0.001). Significant differences in the patients' somatic conditions were not noted between the groups, with the exception of anemia and decreased potassium concentration, which were more frequently observed in women (both p < 0.0001), and of increased concentration of ALT and hypoproteinemia, which were more frequent in men (respectively, p < 0.05 and p < 0.01). Co-existing personality disorders, depressive disorders, and anxiety disorders--as well as abuse of benzodiazepines and barbiturates--were more frequently observed in women (p < 0.0001). The period between the first hospitalization due to alcohol withdrawal and the time of death was significantly shorter in men than in women (p < 0.05). The results point to differences in the conditions and the course of alcohol dependence and alcohol withdrawal between women and men.

Differences in the Course of Alcohol Withdrawal in Women and Men

Differences in the Course of Alcohol Withdrawal in Women and Men

The course of alcohol withdrawal in a general hospital.

We conducted an observational study of 539 episodes of alcohol withdrawal in a general hospital, to determine the natural history, the incidences of seizures, hallucinations and delirium, and the risk factors for these events. The reaction began soon after arrival, at a median time of 5 h, and resolved at a median time of 22 h. Patients with a blood alcohol level of zero were in withdrawal on arrival, and only four patients had reactions lasting 120 h or longer. Complications were observed in 113 patients (21%) during the admission. Seizures occurred on arrival, hallucinations usually in the first 24 h and delirium in the first 48 h. No mortality was associated with alcohol withdrawal itself, but complications did extend length of stay by a median of 4 days, with delirium contributing most to the increase. Patients over 70 years of age or admitted with seizures had an increased risk of complication, but the greatest risk was associated with a delay in assessment of > 24 h. We conclude that in general hospitals, the alcohol withdrawal reaction becomes established very early, and detection and monitoring of patients within the first 24 h is the most important element in management.

Neurochemical correlates of sympathetic activation during severe alcohol withdrawal.

Cerebrospinal fluid (CSF) was obtained from 17 patients during acute alcohol withdrawal. Eight of these 17 patients had a second lumbar puncture a mean of 11.9 +/- 8.1 (SD) days later, when the clinical signs of alcohol withdrawal had subsided. CSF 3-methoxy-4-hydroxyphenylglycol concentrations declined significantly (p < 0.05) during the course of alcohol withdrawal from 52.0 +/- 22.1 (SD) to 39.6 +/- 12.6 pM/ml. In early withdrawal, there was a significant positive correlation between CSF norepinephrine (NE) and corticotropin releasing hormone (CRH) concentrations (r = 0.95, p < 0.001). Both NE and CRH concentrations correlated positively with diastolic blood pressure (r = 0.88, p < 0.001 and r = 0.62, p < 0.05, respectively). In all samples, CSF 5-hydroxyindole acetic acid concentrations correlated positively with CSF-homovanillic acid concentrations (r = 0.83, p < 0.001). These findings indicate significant perturbations of the noradrenergic neuronal system and a change in CRH-NE interactions during acute alcohol withdrawal.