Symptoms Of Alcohol Withdrawal Syndrome Research Articles

Chronic Intermittent Ethanol-Induced Switch of Ethanol Actions from Extrasynaptic to Synaptic Hippocampal GABAAReceptors

Alcohol withdrawal syndrome (AWS) symptoms include hyperexcitability, anxiety, and sleep disorders. Chronic intermittent ethanol (CIE) treatment of rats with subsequent withdrawal of ethanol (EtOH) reproduced AWS symptoms in behavioral assays, which included tolerance to the sleep-inducing effect of acute EtOH and its maintained anxiolytic effect. Electrophysiological assays demonstrated a CIE-induced long-term loss of extrasynaptic GABAA receptor (GABAAR) responsiveness and a gain of synaptic GABAAR responsiveness of CA1 pyramidal and dentate granule neurons to EtOH that we were able to relate to behavioral effects. After CIE treatment, the alpha4 subunit-preferring GABAAR ligands 4,5,6,7 tetrahydroisoxazolo[5,4-c]pyridin-3-ol, La3+, and Ro15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5alpha][1,4]benzodiazepine-3-carboxylate) exerted decreased effects on extrasynaptic currents but had increased effects on synaptic currents. Electron microscopy revealed an increase in central synaptic localization of alpha4 but not delta subunits within GABAergic synapses on the dentate granule cells of CIE rats. Recordings in dentate granule cells from delta subunit-deficient mice revealed that this subunit is not required for synaptic GABAAR sensitivity to low [EtOH]. The profound alterations in EtOH sensitivity and alpha4 subunit localization at hippocampal GABAARs of CIE rats suggest that such changes in these and other relevant brain circuits may contribute to the development of tolerance to the sleep-inducing effects and long-term dependence on alcohol.

Experience with an adult alcohol withdrawal syndrome practice guideline in internal medicine patients.

To standardize treatment of alcohol withdrawal syndrome (AWS) in internal medicine patients using an adult AWS practice guideline with a symptom-triggered management approach. Prospective interventional (pilot group) and retrospective (control group). University teaching hospital. Thirty-two internal medicine patients identified as being at risk for AWS and treated according to the AWS practice guideline who were compared with 49 internal medicine patients managed with nonstandardized approaches. Patients in the pilot group were assessed using the AWS type indicator. They received lorazepam, clonidine, or haloperidol, based on AWS type indicator assessment and adult AWS practice guideline criteria. Data collected and analyzed were drugs administered to control AWS symptoms, use of sitters and physical restraints, length of hospital stay, and discharge from hospital receiving tapered drug therapy. Pilot patients received 46.6% less benzodiazepine (p=0.001), 20% more clonidine (p=0.01), and 18.2% more haloperidol (p=0.002) than control patients. No drug therapy was required in 19% of pilot patients compared with 2% of controls (p=0.01). Significantly more control (71.4%) than pilot patients (18.8%) were discharged with tapered benzodiazepine therapy (p<or=0.01). No significant differences were found between groups for sitters, restraints, or hospital length of stay. This pilot project suggests that internal medicine patients at risk for AWS can be managed with a standardized, symptom-triggered approach using decreased amounts of benzodiazepine in combination with adjunctive agents to treat adrenergic hyperactivity and delirium. Further data are necessary to determine the impact of the practice guideline on patient outcome measurements.

Alcohol withdrawal severity is decreased by symptom-orientated adjusted bolus therapy in the ICU

To examine the effect of bolus vs. continuous infusion adjustment on severity and duration of alcohol withdrawal syndrome (AWS), the medication requirements for AWS treatment, and the effect on ICU stay in surgical intensive care unit (ICU) patients. Prospective randomized, double-blind controlled trial in a surgical ICU. 44 patients who developed AWS after admission to the ICU. Patients were randomized to either (a). a continuous infusion course of intravenous flunitrazepam (agitation), intravenous clonidine (sympathetic hyperactivity), and intravenous haloperidol (productive psychotic symptoms) if needed (infusion-titrated group), or (b). the same medication (flunitrazepam, clonidine, or haloperidol) bolus adjusted in response to the development of the signs and symptoms of AWS (bolus-titrated group). The administration of "as-needed" medication was determined using a validated measure of the severity of AWS (Clinical Institute of Withdrawal Assessment). Although the severity of AWS did not differ between groups initially, it significantly worsened over time in the infusion-titrated group. This required a higher amount of flunitrazepam, clonidine, and haloperidol. ICU treatment was significantly shorter in the bolus-titrated group (median difference 6 days) due to a lower incidence of pneumonia (26% vs. 43%). We conclude that symptom-orientated bolus-titrated therapy decreases the severity and duration of AWS and of medication requirements, with clinically relevant benefits such as fewer days of ventilation, lower incidence of pneumonia, and shorter ICU stay.

L-type Ca 2+ channels mediate cardiovascular symptoms of alcohol withdrawal in humans

The cardiovascular effects and plasma concentrations after intravenous verapamil injection (5 mg) were compared in seven alcohol dependents during alcohol withdrawal syndrome (AWS) to those after resolution of these symptoms. At the onset of AWS, verapamil caused a bradycardiac response, which was absent after resolution of AWS. At the same period, a hypotensive effect of verapamil was weakened. No differences in verapamil plasma concentrations were observed between different periods. These results suggest that L-type Ca 2+ channels are involved in mediating cardiovascular symptoms of AWS.

Long‐Term Effects of and Physiological Responses to Nitrous Oxide Gas Treatment During Alcohol Withdrawal: A Double‐Blind, Placebo‐Controlled Trial

Background Nitrous oxide gas (N2O) has been proposed to be effective in the treatment of the alcohol withdrawal syndrome (AWS). This has not been proved, however, in studies performed according to good clinical practice guidelines. Moreover, previous studies have not measured end tidal N2O concentrations or physiologic responses during N2O treatment. We have recently reported that in a double‐blind, randomized, controlled setting, N2O was not superior to placebo in relieving AWS symptoms. In this previous study, we did not find significant differences between the treatments either in the Clinical Institute Withdrawal Assessment of Alcohol scores or in the total use of benzodiazepines (diazepam and temazepam). The aim of the present study was to characterize other effects and side effects of the N2O treatment using several objective measures and to study the possible long‐term efficacy of the treatment.Methods A total of 105 inpatients who had AWS and were admitted to the A‐Clinic detoxification center were included in the study. The subjects were randomly assigned to one of the following three treatments: (1) N2O/oxygen (from 30 to 70% in oxygen), (2) air/oxygen (30%/70%), and (3) medical (normal) air. During the single 45‐min treatment period, end‐tidal N2O, carbon dioxide, and oxygen concentrations were measured. The physiologic responses were studied by measuring heart rate, blood pressure, pulse oximetric saturation, frontal muscle electromyographic activity, and plethysmographic pulse amplitude. Long‐term effects were studied by measuring craving with the Obsessive‐Compulsive Drinking Scale; severity of dependency with Severity of Alcohol Dependence Data; and liver enzymes with aspartate aminotransferase, alanine aminotransferase, and γ‐glutamyltransferase 3 and 6 months after the treatment.Results Patients in the N2O group demonstrated significantly higher facial muscle electromyographic activity and higher pulse amplitude than the air‐treated subjects. Self‐reported side effects between the gas treatments, however, did not differ between the groups. Regarding long‐term effects of the treatments, there were no differences between the groups.Conclusions Contrary to previously published data, N2O treatment did not decrease craving or liver enzymes during the 6‐month follow‐up. At the concentration used, N2O treatment produced signs of arousal instead of strong sedation.