Selective Blockade of T-Type Ca2+ Channels is Protective Against Alcohol-Withdrawal Induced Seizure and Mortality.

AIMS: We have previously demonstrated that blockade of T-type calcium channels by the non-selective antagonist, ethosuximide (ETX), is effective at reducing electrographical and behavioral correlates of alcohol-withdrawal (WD) seizure. Here, we investigated whether blockade of these calcium channels with the selective antagonist TTA-P2 also reduces alcohol-WD seizure. SHORT SUMMARY: The non-specific T-type calcium channel antagonist, ETX, is protective against alcohol-WD seizure. However, the mechanism of this effect is unclear. Here, we provide evidence that further suggests selective blockade of T-type calcium channels are protective against alcohol-WD seizure and WD-related mortality. METHODS: We used an intermittent ethanol exposure model to produce WD-induced hyperexcitability in DBA/2 J mice. Seizure severity was intensified with the chemoconvulsant pentylenetetrazole (PTZ). RESULTS: TTA-P2 (10 mg/kg) reduced seizure severity in mice undergoing alcohol WD with concurrent PTZ treatment (20 mg/kg). Moreover, TTA-P2 (20 and 40 mg/kg) was also protective against PTZ-induced (40 mg/kg) seizure and mortality. CONCLUSIONS: These results are consistent with prior results using ETX, and suggest that the protective effects of ETX and TTA-P2 against EtOH WD seizures are mediated by T-type calcium channels.

Mortality of subjects with alcohol-related seizures increased after alcohol cheapening.

OBJECTIVE: To investigate whether the reduction of alcohol prices in Finland (March 1, 2004) associated with an increase in mortality of subjects with alcohol-related seizures. PATIENTS AND METHODS: All subjects with head trauma in Oulu University Hospital during 1999 (n = 827) were identified and thereafter followed up until death or the end of 2009. We used National Hospital Discharge Register, hospital charts, and death records from Official Cause-of-Death Statistics to identify seizure visits and alcohol-related deaths. Kaplan-Meier survival curves were used to characterize the effect of alcohol price reduction on risk of death. Cox proportional hazards model was used to identify independent predictors of death. RESULTS: Twenty-five subjects had alcohol-related seizures before the alcohol price reduction. Their cumulative mortality rate was significantly higher (P = 0.015) than that of other head trauma subjects during the follow-up and it clearly increased after the price reduction. Age (HR 1.06 per year, 95% CI 1.05-1.07, P < 0.001), moderate-to-severe traumatic brain injury (HR 2.04 95% CI 1.37-3.04, P < 0.001), and alcohol-related seizure (HR 3.02, 95% CI 1.48-6.16, P = 0.002) were independent predictors of death after adjustment for confounding factors. CONCLUSION: We conclude that the political decision to lower alcohol price associated with a significant increase in the mortality rate of subjects with alcohol-related seizures.

Analysis of the factors determining survival of alcoholic withdrawal syndrome patients in a general hospital.

AIM: To investigate the clinical variables associated with the risk of dying and the causes of death during the course of alcoholic withdrawal syndrome (AWS) in a general hospital. METHODS: Cohort study of AWS patients admitted to Xeral Hospital in Lugo, Spain between 1987 and 2003. The characteristics of patients who died were contrasted with those who survived. The different clinical, epidemiological and biochemical variables reflective of alcohol consumption habits, basal health status and presentation features of the syndrome and its complications were all recorded. RESULTS: There were 539 episodes of hospitalization for AWS in 436 patients (mean age 45.0, SD 12.0, 91.3% males), 71.1% of whom presented with delirium tremens. A total of 29 patients died, yielding a 6.6% mortality rate (95% confidence interval, CI: 4.2-9.1%). Eighteen patients (62%) died after being admitted to the intensive care unit (ICU). The following independent variables were associated with the risk of dying in a multivariate logistic regression model: cirrhosis [odds ratio (OR) 4.8 (95% CI 1.5-14.6), P = 0.006]; presenting with delirium tremens at diagnosis [OR 3.5 (95% CI 1.3-8.9), P = 0.008]; the existence of an underlying chronic pathology other than liver disease [OR 2.5 (95% CI 1-6.1), P = 0.01]; and the need for orotracheal intubation [OR 2.9 (95% CI 1.1-7.9), P = 0.03], especially if pneumonia requiring ICU is added [OR 8 (95% CI 3-21.3), P < 0.001]. Receiver operating characteristic analysis revealed an area under the curve of 0.818 (95% CI 0.742-0.894). CONCLUSIONS: The factors determining survival after admission to a general hospital for alcoholic withdrawal syndrome depend on the intensity of clinical manifestations (delirium tremens, ICU, orotracheal intubation) and the presence of associated comorbidity.