A machine learning approach to risk assessment for alcohol withdrawal syndrome.

At present, risk assessment for alcohol withdrawal syndrome relies on clinical judgment. Our aim was to develop accurate machine learning tools to predict alcohol withdrawal outcomes at the individual subject level using information easily attainable at patients' admission. An observational machine learning analysis using nested cross-validation and out-of-sample validation was applied to alcohol-dependent patients at two major detoxification wards (LMU, n = 389; TU, n = 805). 121 retrospectively derived clinical, blood-derived, and sociodemographic measures were used to predict 1) moderate to severe withdrawal defined by the alcohol withdrawal scale, 2) delirium tremens, and 3) withdrawal seizures. Mild and more severe withdrawal cases could be separated with significant, although highly variable accuracy in both samples (LMU, balanced accuracy [BAC] = 69.4%; TU, BAC = 55.9%). Poor outcome predictions were associated with higher cumulative clomethiazole doses during the withdrawal course. Delirium tremens was predicted in the TU cohort with BAC of 75%. No significant model predicting withdrawal seizures could be found. Our models were unique to each treatment site and thus did not generalize. For both treatment sites and withdrawal outcome different variable sets informed our models' decisions. Besides previously described variables (most notably, thrombocytopenia), we identified new predictors (history of blood pressure abnormalities, urine screening for benzodiazepines and educational attainment). In conclusion, machine learning approaches may facilitate generalizable, individualized predictions for alcohol withdrawal severity. Since predictive patterns highly vary for different outcomes of withdrawal severity and across treatment sites, prediction tools should not be recommended for clinical practice unless adequately validated in specific cohorts.

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.

Alcohol withdrawal upregulates mRNA encoding for CaV2.1-α1 subunit in the rat inferior colliculus.

We previously reported increased current density through P-type voltage-gated Ca2+ channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased P-type channel current is currently unknown. Here, we probe changes in mRNA and protein expression of the pore-forming CaV2.1-α1 (P/Q-type) subunits in IC neurons during the course of alcohol withdrawal-induced seizures (AWSs). Rats received three daily doses of ethanol or the vehicle every 8 h for 4 consecutive days. The IC was dissected at various time intervals following alcohol withdrawal, and the mRNA and protein levels of the CaV2.1-α1 subunits were measured. In separate experiments, rats were tested for acoustically evoked seizure susceptibility 3, 24, and 48 h after alcohol withdrawal. AWSs were observed 24 h after withdrawal; no seizures were observed at 3 or 48 h or in the control-treated rats. Compared to control-treated rats, the mRNA levels of the CaV2.1-α1 subunit were increased 1.9-fold and 2.1-fold at 3 and 24 h, respectively; change in mRNA expression was nonsignificant at 48 h following alcohol withdrawal. Western blot analyses revealed that protein levels of the CaV2.1-α1 subunits were not altered in IC neurons following alcohol withdrawal. We conclude that expression of the Cacna1a mRNA increased before the onset of AWS susceptibility, suggesting that altered CaV2.1 channel expression may play a role in AWS pathogenesis.

Convulsões relacionadas ao alcoolismo: atualização / Seizures related to alcoholism: update

OBJETIVO: Revisão sobre crises convulsivas relacionadas ao alcoolismo,discutindo sua classificação, fisiopatologia, investigação diagnóstica e seu tratamento. MÉTODO: Revisão não sistemática de artigos utilizando-se os unitermos: "alcoholism", "alcohol", "seizures" e "withdrawal". Priorizou-se a utilização de artigos que apresentassem associação desses unitermos no título. Foram utilizadas as bases de dados do PubMed, Lilacs e Google Scholar. RESULTADOS: Foram encontrados 2.362 artigos associando os unitermos no título, tendo sido escolhidos 26 artigos em inglês, 3 em português, 1 manual e 1 tese em inglês para a elaboração desta revisão. CONCLUSÃO: As crises convulsivas relacionadas ao álcool representam uma das mais graves complicações do alcoolismo. O diagnóstico e o tratamento corretos melhoram o prognóstico desses indivíduos, diminuindo o risco de complicações, a recorrência de crises, a ocorrência de status epilepticus ou a evolução para um quadro de delirium tremens.

OBJECTIVE: Review alcoholism related seizures, discussing classification,pathophysiology, diagnosis and treatment. METHOD: A non-systematic review was performed of articles using the keywords: "alcoholism", "alcohol", "seizures", and "withdrawal". Articles with the combination of these keywords in the title were favored. The search was performed on PubMed, Lilacs database and Google Scholar. RESULTS: Using these search terms 2,362 articles were found, being selected 26 articles in English, 3 articles in Portuguese, 1 English manual, and 1 thesis in English to elaborate this review. CONCLUSION: Seizures related to alcohol are one of the most serious complications of alcoholism. The correct diagnosis and treatment improves the prognosis of these individuals, decreasing the risk of complications,seizure recurrence, status epilepticus and the progression to delirium tremens.

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 Ca(2+) (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.

Predictive value of the bispectral index for burst suppression on diagnostic electroencephalogram during drug-induced coma.

STUDY PURPOSE: To determine correlation and predictive value between data obtained with the bispectral index (BIS) and diagnostic electroencephalogram (EEG) in determining degree of burst suppression during drug-induced coma. This study seeks to answer the question: "To what degree can EEG suppression and burst count as measured by diagnostic EEG during drug-induced coma be predicted from data obtained from the BIS such as BIS value, suppression ratio (SR), and burst count?" BACKGROUND/SIGNIFICANCE: During drug-induced coma, cortical EEG is the gold standard for real-time monitoring and drug titration. Diagnostic EEG is, from setup through data analysis, labor intensive, costly, and difficult to maintain uniform clinician competency. BIS monitoring is less expensive, less labor-intensive, and easier to interpret data and establish/maintain competency. Validating BIS data versus diagnostic EEG facilitates effective brain monitoring during drug-induced coma at lower cost with similar outcomes. METHOD: This is a prospective, observational cohort study. Four consecutive patients receiving drug-induced coma/EEG monitoring were enrolled. BIS was initiated after informed consent. Variables recorded per minute included presence or absence of EEG burst suppression, burst count, BIS value over time, burst count, and SR. Pearson's product-moment and Spearman rank coefficient for BIS value and SR versus burst count were performed. Regression analysis was utilized to plot BIS values versus bursts/minute on EEG as well as SR versus burst count on EEG. EEG/BIS data were collected from digital data files and transcribed onto data sheets for corresponding time indices. RESULTS: Four patients yielded 1,972 data sets over 33 hours of EEG/BIS monitoring. Regression coefficient of 0.6673 shows robust predictive value between EEG burst count and BIS SR. Spearman rank coefficient of -0.8727 indicates strong inverse correlation between EEG burst count and BIS SR. Pearson's correlation coefficient between EEG versus BIS burst count was .8256 indicating strong positive correlation. Spearman's rank coefficient of 0.8810 and Pearson's correlation coefficient of .6819 showed strong correlation between BIS value versus EEG burst count. Number of patients (4) limits available statistics and ability to generalize results. Graphs and statistics show strong correlation/predictive value for BIS parameters to EEG suppression. CONCLUSIONS: This study is the first to measure correlation and predictive value between BIS monitoring and diagnostic EEG for degree of EEG suppression and burst count in the adult population. Available statistic tests and graphing of variables from BIS and diagnostic EEG show strong correlation and predictive value between both monitoring technologies during drug-induced coma. These support using BIS value, SR, and burst count to predict degree of EEG suppression in real time for titrating metabolic suppression therapy.

Understanding the addiction cycle: a complex biology with distinct contributions of genotype vs. sex at each stage.

Ethanol abuse can lead to addiction, brain damage and premature death. The cycle of alcohol addiction has been described as a composite consisting of three stages: intoxication, withdrawal and craving/abstinence. There is evidence for contributions of both genotype and sex to alcoholism, but an understanding of the biological underpinnings is limited. Utilizing both sexes of genetic animal models with highly divergent alcohol withdrawal severity, Withdrawal Seizure-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) mice, the distinct contributions of genotype/phenotype and of sex during addiction stages on neuroadaptation were characterized. Transcriptional profiling was performed to identify expression changes as a consequence of chronic intoxication in the medial prefrontal cortex. Significant expression differences were identified on a single platform and tracked over a behaviorally relevant time course that covered each stage of alcohol addiction; i.e., after chronic intoxication, during peak withdrawal, and after a defined period of abstinence. Females were more sensitive to ethanol with higher fold expression differences. Bioinformatics showed a strong effect of sex on the data structure of expression profiles during chronic intoxication and at peak withdrawal irrespective of genetic background. However, during abstinence, differences were observed instead between the lines/phenotypes irrespective of sex. Confirmation of identified pathways showed distinct inflammatory signaling following intoxication at peak withdrawal, with a pro-inflammatory phenotype in females but overall suppression of immune signaling in males. Combined, these results suggest that each stage of the addiction cycle is influenced differentially by sex vs. genetic background and support the development of stage- and sex-specific therapies for alcohol withdrawal and the maintenance of sobriety.

Alcohol and drugs in epilepsy: pathophysiology, presentation, possibilities, and prevention.

The potentially serious outcomes from ingestion of and dependence on toxins make this an important topic for epileptologists. We must be aware of the potential for harm from compounds that may be freely available, yet patients may try to conceal their use. Problematic compounds may cause seizures either acutely or on withdrawal: Their use may reduce effectiveness of antiepileptic drugs, or may simply promote and enhance chaotic lifestyles. Any or all of these factors may worsen seizure control or even directly cause seizures. This article highlights the pathophysiology behind provoked seizures, provides clues to diagnosis, and then outlines the steps that clinicians should take to reduce the deleterious effects of toxic compounds.

Indicators for elevated risk factors for alcohol-withdrawal seizures: an analysis using a random forest algorithm.

Alcohol-withdrawal seizures (AWS) are an important and relevant complication during detoxification in alcohol-dependent patients. Therefore, it is important to evaluate the individual risk for AWS. We apply a random forest algorithm to assess possible predictive markers in a large sample of 200 alcohol-dependent patients undergoing alcohol withdrawal. This analysis showed that the combination of homocysteine, prolactin, blood alcohol concentration on admission, number of preceding withdrawals, age and the number of cigarettes smoked may successfully predict AWS. In conclusion, the results of this analysis allow for origination of further research, which should include additional biological and psychosocial parameters as well as consumption behaviour.

Running wheel activity protects against increased seizure susceptibility in ethanol withdrawn male rats.

Ethanol withdrawal is a dysphoric condition that arises from termination of ethanol intake by dependent individuals. Common withdrawal symptoms include anxiety, increased reactivity to stimuli and increased seizure susceptibility as well as the risk of increased seizure severity. We use an animal model of dependence and withdrawal to study withdrawal behaviors and potential underlying neurobiological mechanisms. For a number of years, we have quantified pentylenetetrazol seizure thresholds as an assessment of ethanol withdrawal at both one day and three days of withdrawal. Typically, we see a significant decrease in seizure threshold (increased sensitivity to seizure induction) that persists through three days of withdrawal for male rats. Increasing evidence indicates that voluntary exercise affords protection against various challenges to physical and psychological health, including ethanol-related challenges. Therefore, the current study investigated the effect of voluntary wheel running on seizure susceptibility following chronic ethanol administration and withdrawal. We found that voluntary wheel running attenuated the increased sensitivity to pentylenetetrazol-induced seizures observed with ethanol withdrawal, at both the one-day and three-day time points. This result was especially interesting as animals with access to the running wheels consumed more of the ethanol-containing diet. These findings showed that chronic voluntary wheel running reduces the severity of ethanol withdrawal in our animal model and suggest that exercise-based interventions may have some utility in the clinical management of heavy drinking and alcohol withdrawal.

[Treatment of alcohol withdrawal symptoms]. / Alkoholivieroitusoireiden hoito.

In the summer, alcohol consumption increases and the number of those requiring rehabilitation peaks at the end of the holiday season. Treatment of alcohol withdrawal symptoms early enough helps the patient to break the drinking cycle. Treatment of alcohol withdrawal symptoms will also prevent complications, such as convulsions and alcoholic delirium. Untreated alcoholic delirium is a life-threatening condition. Treatment aims to calm down the hyperactivity state of the autonomous nervous system, and correct electrolyte and fluid balance disturbances. Initiation of rehabilitation is determined by the severity of the patient's withdrawal symptoms. Benzodiazepines are the first-line drugs.

Persistent escalation of alcohol drinking in C57BL/6J mice with intermittent access to 20% ethanol.

BACKGROUND: Intermittent access (IA) to drugs of abuse, as opposed to continuous access, is hypothesized to induce a kindling-type transition from moderate to escalated use, leading to dependence. Intermittent 24-hour cycles of ethanol access and deprivation can generate high levels of voluntary ethanol drinking in rats. METHODS: The current study uses C57BL/6J mice (B6) in an IA to 20% ethanol protocol to escalate ethanol drinking levels. Adult male and female B6 mice were given IA to 20% ethanol on alternating days of the week with water available ad libitum. Ethanol consumption during the initial 2 hours of access was compared with a short-term, limited access "binge" drinking procedure, similar to drinking-in-the-dark (DID). B6 mice were also assessed for ethanol dependence with handling-induced convulsion, a reliable measure of withdrawal severity. RESULTS: After 3 weeks, male mice given IA to ethanol achieved high stable levels of ethanol drinking in excess of 20 g/kg/24 h, reaching above 100 mg/dl blood ethanol concentrations, and showed a significantly higher ethanol preference than mice given continuous access to ethanol. Also, mice given IA drank about twice as much as DID mice in the initial 2-hour access period. B6 mice that underwent the IA protocol for longer periods of time displayed more severe signs of alcohol withdrawal. Additionally, female B6 mice were given IA to ethanol and drank significantly more than males (ca. 30 g/kg/24 h). DISCUSSION: The IA method in B6 mice is advantageous because it induces escalated, voluntary, and preferential per os ethanol intake, behavior that may mimic a cardinal feature of human alcohol dependence, though the exact nature and site of ethanol acting in the brain and blood as a result of IA has yet to be determined.

Subacute encephalopathy and seizures in alcoholics (SESA) presenting with non-convulsive status epilepticus.

Subacute encephalopathy with seizures in chronic alcoholism (SESA) was first described in 1981 by Niedermeyer who reported alcoholic patients presenting with confusion, seizures and focal neurological deficits and is quite distinct from patients presenting with typical alcohol withdrawal seizures. EEG often reveals periodic discharges and spikes, but SESA presenting with non-convulsive status epilepticus has rarely been described. We report a case of SESA with non-convulsive status epilepticus in a patient who was initially suspected of having a typical alcohol withdrawal seizure. A 61 year old woman with a history of chronic alcoholism was admitted at an outside hospital for confusion thought to be secondary to an alcohol withdrawal seizure. She had right hemiparesis and later developed right facial twitching that did not respond to intravenous fosphenytoin and levetiracetam. She was transferred for further management. Upon arrival, lorazepam and fosphenytoin were given and right face clonic movements resolved. However, continuous EEG monitoring revealed ongoing non-convulsive status epilepticus (NCSE). Following treatment with IV valproate and lacosamide, there was resolution of NCSE. SESA is likely an under recognized clinical syndrome that is quite distinct from typical alcohol withdrawal seizures and requires a different diagnostic and management approach. NCSE is likely to account for the encephalopathy and focal neurological deficits seen in patients presenting with the clinical syndrome of SESA. Therefore, a high degree of suspicion is warranted and continuous EEG monitoring is recommended for alcoholic patients with encephalopathy and focal neurological deficits.

Quantitative EEG in patients with alcohol-related seizures.

BACKGROUND: To investigate whether quantitative electroencephalography (QEEG) recorded within a few days after a generalized seizure can improve the discrimination between alcohol-related seizures (ARSs), seizures in epilepsy and other seizures. In addition, we wanted to evaluate the influence of various external factors on QEEG, e.g., drug use, time from seizure occurrence, and alcohol intake. METHODS: An ARS was defined by (i) scores ≥8 in the Alcohol Use Disorders Identification Test (AUDIT) and (ii) no history of epilepsy. Twenty-two ARS patients, 21 epileptic patients with seizures (ES), 30 AUDIT-negative patients with seizures (OS), and 37 well-controlled epileptic outpatients (EPO) were included. EEG from 79 sciatica patients (SC) served as an additional control group. EEG was recorded in relaxed wakefulness with eyes closed. Spectral analysis of ongoing resting EEG activity was performed. For the main analysis, spectral band amplitudes were averaged across 14 electrodes. RESULTS: Major quantitative EEG abnormalities were mainly seen in the ES group. AUDIT score correlated negatively with QEEG band amplitudes in patients with seizures unrelated to alcohol, but not in the ARS group. Recent alcohol intake correlated negatively with delta and theta amplitude. We could not confirm that beta activity is increased in ARS subjects. CONCLUSIONS: A QEEG with slightly reduced alpha amplitude supports a clinical diagnosis of ARS. An abnormally slow QEEG profile and asymmetry in the temporal regions indicates ES. QEEG predicted the clinical diagnosis better than standard EEG.

The EEG response to photic stimulation is not increased in alcohol-related seizures.

OBJECTIVE: To investigate the occipital EEG response to 18 and 24Hz photic stimulation (the H-response) in alcohol-related seizures (ARS). METHOD: Twenty-two ARS patients, 15 of whom had a withdrawal seizure (WS) were compared with patients with recent seizures of other causes: 21 patients with epilepsy, and 30 Alcohol Use Disorders Identification Test (AUDIT) negative patients with other seizures. EEG from 37 out-patients with epilepsy and 79 sciatica patents served as patient-controls. The spectral amplitude around 18 and 24Hz and a new photic H-ratio (24/18Hz relative amplitude) was calculated. RESULTS: The H-ratio was significantly reduced in the ARS group compared to the sciatica group. H-ratio reduction correlated with the AUDIT score in ARS patients (p=0.02). No differences between WS and non-WS patients were found for H-response variables. CONCLUSION: A dose-response relationship between AUDIT and the photic response H-ratio was observed in ARS patients. The EEG-driving response to 24Hz flashes was not increased in ARS. SIGNIFICANCE: The relative decrease in 24Hz photic response in ARS reflected drinking severity. The H-ratio is a candidate biomarker for ARS on the group level, although the moderate effect size precludes its use in individual patients.

Sex differences in acoustic startle responses and seizure thresholds between ethanol-withdrawn male and female rats.

AIMS: We have found consistent and significant sex differences in recovery from the increased seizure susceptibility observed during ethanol withdrawal (EW) in our rat model system. The main objective of the present study was to determine if sex differences in EW generalized to an additional behavioral measure startle reactivity. METHODS: Acoustic startle or seizure threshold responses were measured in separate groups of rats at 1 day or 3 days of EW. RESULTS: Both pair-fed control and EW males showed greater increases in acoustic startle responses than either the female or ovariectomized female (OVX) counterparts. There was a selective effect of pregnanolone on acoustic startle in that it reduced peak force of response only at 3 days EW in male rats. Unexpectedly, it modestly increased startle reactivity in control female and OVX rats. Acute treatment with low-dose ethanol trended toward reducing startle responses in control animals, as expected, while generally enhancing startle responses during EW. All sex conditions showed an enhanced startle response during EW following administration of the higher dose of estradiol compared to control animals. Estradiol did not alter seizure thresholds in control animals. However, it was anticonvulsant for males at 3 days EW, females and OVX at 1 day EW. CONCLUSIONS: Observed sex differences in the startle reactivity during EW were consistent with earlier findings comparing EW seizure risk in male and female rats. Responses of OVX suggested that both hormones and differences in brain structures between males and females have a role in these sex differences. Our findings add weight to recommendations that treatment of alcohol withdrawal in humans should consider hormonal status as well as withdrawal time.

Sex differences in acute ethanol withdrawal severity after adrenalectomy and gonadectomy in Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant mice.

Recent findings suggest that the ability of ethanol (EtOH) to increase the levels of neurosteroids with potent gamma-aminobutyric acid (GABA)ergic properties can influence measures of EtOH sensitivity. Earlier studies determined that removal of the adrenals and gonads diminished the steroidogenic effect of EtOH and significantly increased acute EtOH withdrawal severity in two inbred mouse strains that differed in withdrawal severity, suggesting the contribution of anticonvulsant GABAergic steroids to acute withdrawal in intact animals. Thus, the goal of the present study was to investigate the consequence of steroid removal on acute EtOH withdrawal through excision of the adrenals and gonads, in another genetic animal model of EtOH withdrawal differences, the Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) selected lines. Male and female WSP and WSR mice underwent surgical removal of the adrenals and gonads or no organ removal (SHAM). One to 2 weeks later, baseline handling-induced convulsions (HICs) were assessed, mice were given a 4 g/kg dose of EtOH, and HICs were measured hourly for 12 h and then at 24 h. The combination surgery significantly increased EtOH withdrawal in WSP and WSR female mice, as measured by area under the curve (AUC) and peak HIC scores. The AUC was significantly positively correlated with plasma corticosterone levels and significantly negatively correlated with progesterone levels. In contrast, surgical status did not alter withdrawal severity in male WSP and WSR mice. Overall, the increase in acute EtOH withdrawal severity in female WSP and WSR mice after adrenalectomy and gonadectomy corroborate our recent evidence that withdrawal from a high dose of EtOH can be modulated by anticonvulsant steroids produced in the periphery.

Preclinical evaluation of riluzole: assessments of ethanol self-administration and ethanol withdrawal symptoms.

BACKGROUND: Many of the neurobehavioral effects of ethanol are mediated by inhibition of excitatory N-methyl-D-aspartate (NMDA) and enhancement of inhibitory gamma-amino-butyric-acid (GABA) receptor systems. There is growing interest in drugs that alter these systems as potential medications for problems associated with alcoholism. The drug riluzole, approved for treatment of amyotrophic lateral sclerosis (ALS), inhibits NMDA and enhances GABA(A) receptor system activity. This study was designed to determine the preclinical efficacy of riluzole to modulate ethanol self-administration and withdrawal. METHODS: Male C57BL/6J mice were trained to lever press on a concurrent fixed-ratio 1 schedule of ethanol (10% v/v) versus water reinforcement during daily 16-hour sessions. Riluzole (1 to 40 mg/kg, IP) was evaluated on ethanol self-administration after acute and chronic (2 week) treatment. To determine if riluzole influences ethanol withdrawal-associated seizures, mice were fed an ethanol-containing or control liquid diet for 18 days. The effects of a single injection of riluzole (30 mg/kg) were examined on handling-induced convulsions after ethanol withdrawal. RESULTS: Acute riluzole (30 and 40 mg/kg) reduced ethanol self-administration during the first 4 hours of the session, which corresponds to the known pharmacokinetics of this drug. Ethanol self-administration was also reduced by riluzole after chronic treatment. Riluzole (30 mg/kg) significantly decreased the severity of ethanol-induced convulsions 2 hours after ethanol withdrawal. CONCLUSIONS: These results demonstrate that riluzole decreases ethanol self-administration and may reduce ethanol withdrawal severity in mice. Thus, riluzole may have utility in the treatment of problems associated with alcoholism.

Substance abuse and withdrawal in the critical care setting.

Substance use is common among individuals admitted to the critical care setting and may complicate treatment of underlying disorders. It is imperative for the critical care team to have a high index of suspicion for substance intoxication and withdrawal. This article reviews the epidemiology of substance use in this population and the treatment of common withdrawal syndromes. General principles regarding the management of substance withdrawal syndromes include general resuscitative measures, use of a symptom-triggered approach, and substitution of a long-acting replacement for the abused drug in gradual tapering dose. The authors stress the importance of long-term planning as part of the overall treatment protocol beyond the acute presentation.