Therapy For Alcohol Withdrawal Syndrome Research Articles

Effects of CYP2C19*17 genetic polymorphisms on plasma and saliva concentrations of diazepam in patients with alcohol withdrawal syndrome.

Diazepam is one of the most commonly prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS). However, diazepam therapy often turns out to be ineffective, and some patients experience dose-dependent adverse drug reactions. Previous studies have shown that the metabolism of diazepam involves the CYP2C19 isoenzyme, whose activity is highly dependent on polymorphism of the encoding gene. The study aimed to investigate the effects of CYP2C19*17 genetic polymorphisms on plasma and saliva concentrations of diazepam as well as its impact on the efficacy and safety rates of therapy in patients with AWS. The study was conducted on 100 Russian male patients suffering from the AWS who received diazepam injections at a dosage of 30.0 mg/day for 5 days. Genotyping was performed by real-time PCR with allele-specific hybridization. The efficacy and safety assessment was performed using psychometric scales. Based on the results of the study, we revealed differences in the efficacy and safety of therapy in patients with different CYP2C19 -806C>T genotypes. Therapeutic drug monitoring revealed the statistically significant difference in the levels of diazepam plasma concentration: (CC) 251.76 (214.43; 310.61) vs. (CT+TT) 89.74 (54.18; 179.13); P = 0.003, and diazepam saliva concentration: (CC) 3.86 (3.22; 5.12) vs. (CT+TT) 0.79 (0.44; 1.56); P = 0.003. Our study showed the effects of CYP2C19*17 genetic polymorphisms on the efficacy and safety rates of diazepam. Furthermore, we revealed the statistically significant differences in plasma and saliva concentration levels of diazepam in patients carrying different genotypes.

Relations of CYP2C19*2 genetic polymorphisms to plasma and saliva concentrations of diazepam in patients hospitalized for alcohol withdrawal

Diazepam is one of the most widely prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS). However, diazepam therapy often turns out to be ineffective, and some patients experience dose-dependent adverse drug reactions. Previous studies have shown that the metabolism of diazepam involves the CYP2C19 isoenzyme, whose activity is highly dependent on polymorphism of the encoding gene. The objective of our study was to investigate the effects of CYP2C19*2 genetic polymorphisms on plasma and saliva concentrations of diazepam as well as its impact on the efficacy and safety rates of therapy in patients with AWS. The study was conducted on 100 Russian male patients with AWS who received diazepam in injections at a dosage of 30.0 mg/day for 5 days. Genotyping was performed by real-time polymerase chain reaction. The efficacy and safety assessment was performed using psychometric scales. We revealed differences in the efficacy and safety of therapy in patients with different CYP2C19 681G>A genotypes. Therapeutic drug monitoring (TDM) revealed the statistically significant differences in the levels of diazepam plasma concentration: (GG) 199.83 [82.92; 250.58] vs (GA+AA) 313.47 [288.99; 468.33], p=0.040, and diazepam saliva concentration: (GG) 2.80 [0.73; 3.80] vs (GA+AA) 5.33 [5.14; 6.00], p=0.003).

Using the CYP3A Activity Evaluation to Predict the Efficacy and Safety of Diazepam in Patients With Alcohol Withdrawal Syndrome

Background: Diazepam is one of the most commonly prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on the efficacy and safety of diazepam therapy. Objective: The objective of our study was to study the effect of CYP3A isoenzymes activity on the efficacy and safety of diazepam in patients with AWS. Methods: The study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg / day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Results: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP3A4 C>T intron 6 (rs35599367) genotypes: (CC) −9.0 [−13.0; −5.0], (CT+TT) −13.5 [−15.0; −10.0], p = 0.014. The scores on the UKU scale, which was used to evaluate the safety of therapy, were also different: (CC) 7.5 [6.0; 11.0], (CT+TT) 11.0 [8.0; 12.0], p = 0.003. Conclusion: Possible relationship between the CYP3A activity, evaluated by the content of the urinary endogenous substrate of the given isoenzyme and its metabolite, the 6-beta-hydroxy cortisol (6-β-HC) / cortisol ratio, and the efficacy of diazepam was demonstrated. This possible relationship was also supported by the genotyping results. This should be taken into consideration when prescribing this drug to such patients in order to reduce the risk of pharmacoresistance.

Alcohol as a Means for the Prevention of Disturbances in Surgical Intensive Care Medicine

Surgical treatment of patients with alcohol use disorder can lead to disturbances (withdrawal syndrome, delirium) which require intensive care treatment. In a surgical ward, the diagnosis of an alcohol related disorder is not always simple. Oftentimes patients conceal or trivialize the issue and as a result are admitted to the hospital in a non-abstinent or unstable state. It is risky to assume that patients with alcohol use disorder will successfully be supplied with alcohol in general hospitals. The risk can be reduced through presurgical identification and alcohol withdrawal of such patients. A literature review concludes that there is no secured evidence for the application of alcohol as prophylaxis or therapy of alcohol withdrawal syndrome in a surgical intensive care unit. The use of intravenous and oral alcohol in intensive care is an unnecessary risk to patients. There are more secure alternatives.

Phenobarbital Monotherapy for the Management of Alcohol Withdrawal Syndrome in Surgical-Trauma Patients.

Benzodiazepine is first-line therapy for alcohol withdrawal syndrome (AWS), and phenobarbital is an alternative therapy. However, its use has not been well validated in the surgical-trauma patient population. To describe the use of fixed-dose phenobarbital monotherapy for the management of patients at risk for AWS in the surgical-trauma intensive care unit. Surgical-trauma critically ill patients who received phenobarbital monotherapy, loading dose followed by a taper regimen, for the management of AWS were included in this evaluation. The effectiveness of phenobarbital monotherapy to treat AWS and prevent development of AWS-related complications were evaluated. Safety end points assessed included significant hypotension, bradycardia, respiratory depression, and need for invasive mechanical ventilation. A total of 31 patients received phenobarbital monotherapy; the majority of patients were at moderate risk for developing AWS (n = 20; 65%) versus high risk (n = 11; 35%). None of the patients developed AWS-related complications; all patients were successfully managed for their AWS. Nine patients (29%) received nonbenzodiazepine adjunct therapy for agitation post-phenobarbital initiation. Three patients (10%) experienced hypotension, and 3 (10%) were intubated. None of the patients had clinically significant bradycardia or respiratory depression. Fixed-dose phenobarbital monotherapy appears to be well tolerated and effective in the management of AWS. Further evaluation is needed to determine the extent of benefit with the use of phenobarbital monotherapy for management of AWS.

Effects of CYP2C19*17 Genetic Polymorphisms on the Steady-State Concentration of Diazepam in Patients With Alcohol Withdrawal Syndrome.

Background: Diazepam is one of the most widely prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS), which includes the symptoms of anxiety, fear, and emotional tension. However, diazepam therapy often turns out to be ineffective, and some patients experience dose-dependent adverse drug reactions, reducing the efficacy of therapy. Aim: The purpose of our study was to investigate the effects of CYP2C19*17 genetic polymorphisms on the steady-state concentration of diazepam in patients with AWS. Materials and Methods: The study was conducted on 50 Russian male patients suffering from the AWS. For the therapy of psychomotor agitation, anxiety, fear, and emotional tension, patients received diazepam in injections at a dosage of 30.0 mg/day for 5 days. Genotyping was performed by real-time polymerase chain reaction. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Therapeutic drug monitoring (TDM) was performed using the high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. Results: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 -806C>T genotypes: (*1/*1) -12.0 [-15.0; -8.0], (*1/*17+*17/*17) -7.0 [-14.0; -5.0], P < .001, as well as the results of TDM: (CC) 250.70 [213.34; 308.53] ng/mL (*1/*17+*17/*17) 89.12 [53.26; 178.07] ng/mL, P < .001. Conclusion: Thus, our study enrolling 50 patients with AWS, showed the effects of CYP2C19*17 genetic polymorphisms on the efficacy and safety rates of diazepam. Furthermore, we revealed the statistically significant difference in the levels of plasma steady-state concentrations of diazepam in patients carrying different genotypes.

How do CYP2C19*2 and CYP2C19*17 genetic polymorphisms affect the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome?

Background Diazepam is one of the most commonly prescribed tranquilizers for therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on its efficacy and safety. The objective of our study was to investigate the effect of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy and safety of diazepam in patients with AWS. Methods The study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg/day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Results Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 681G>A (CYP2C19*2, rs4244285) genotypes: (CYP2C19*1/*1) -8.5 [-15.0; -5.0], (CYP2C19*1/*2 and CYP2C19*2/*2) -12.0 [-13.0; -9.0], p = 0.021. The UKU scale scores, which were used to evaluate the safety of therapy, were also different: (CYP2C19*1/*1) 7.0 [6.0; 12.0], (CYP2C19*1/*2 and CYP2C19*2/*2) 9.5 [8.0; 11.0], p = 0.009. Patients carrying different CYP2C19 -806C>T (CYP2C19*17, rs12248560) genotypes also demonstrated differences in therapy efficacy and safety rates. Conclusions Thus, the effects of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy of diazepam were demonstrated.

Symptom-Triggered Therapy for Alcohol Withdrawal Syndrome: a Systematic Review and Meta-analysis of Randomized Controlled Trials.

Benzodiazepines are the standard medication class for treating alcohol withdrawal. Guidelines recommend dosing based on objectively measured symptoms (symptom-triggered therapy) rather than fixed dose regimens. However, the superiority of symptom-triggered therapy has been questioned, and concerns have been raised about its inappropriate use and safety. We aimed to assess whether symptom-triggered therapy is superior to fixed dose schedules in terms of mortality, delirium, seizures, total benzodiazepine dose, and duration of therapy. A systematic literature search using Medline, Embase, and the Cochrane Registry through February 2018 was conducted for randomized controlled trials of patients with alcohol withdrawal syndrome comparing fixed dose benzodiazepine schedules to symptom-triggered therapy. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Outcomes were pooled using random effects meta-analysis. Heterogeneity was estimated using the I2 statistic. Strength of evidence was assessed using methods outlined by the Agency for Healthcare Research and Quality. Six studies involving 664 patients were included. There were no deaths and only one seizure in each group. Four studies reported delirium, which occurred in 4 out of 164 patients randomized to symptom-triggered therapy compared to 6 out of 164 randomized to fixed dose therapy (odds ratio, 0.64 [95% CI, 0.17-2.47]). Three studies reported duration of therapy, which was 60.4h less with symptom-triggered therapy (95% CI, 39.7-81.1h; p < 0.001). Six studies reported total benzodiazepine dosage, which was 10.5mg in lorazepam-equivalent dosing less with symptom-triggered therapy (95% CI, 7.1-13.9mg; p = 0.011). Moderate strength evidence suggests that symptom-triggered therapy improved duration of therapy and total benzodiazepine dose in specialized detoxification settings of low-risk patients but the applicability of this evidence in general hospital settings is low. There was insufficient evidence for any conclusions about symptom-triggered therapy for the major outcomes of mortality, seizure, and delirium in any setting. CRD42017073426.

Effect of early and focused benzodiazepine therapy on length of stay in severe alcohol withdrawal syndrome

Objective: Current evidence supports symptom-triggered therapy for alcohol withdrawal syndrome (AWS). Early, escalating therapy with benzodiazepines (BZD) appears to decrease ICU length of stay (LOS); however, the effect on hospital LOS remains unknown. The hypothesis of this study is that focused BZD treatment in the first 24 h will decrease hospital LOS.Design: Pre–post cohort study.Setting: Academic medical center.Patients: This study included patients with severe AWS. The pre-intervention cohort (PRE) was admitted between January and November 2015. The post-intervention cohort (POST) was admitted between April 2016 and March 2017. Severe AWS was defined as patients requiring diazepam doses of >30 mg. Focused treatment was defined as >50% of total diazepam usage within the first 24 h of recognition of AWS.Intervention: In the PRE group, patients received symptom-triggered, escalating doses of diazepam and phenobarbital based on their Richmond Agitation-Sedation Scale (RASS). In the POST group, patients received a revised, time-limited course of therapy: escalating doses of BZD and phenobarbital were given during a 24-h loading phase, and all therapy was discontinued after a 72-h tapering phase. The SHOT scale was used as an adjunct to RASS to assess non-agitation symptoms of AWS and guide additional diazepam doses.Measurements and main results: The primary outcome was hospital LOS; secondary outcomes included ICU LOS, BZD use, and ventilator-free days. Five hundred thirty-two patients were treated using the AWS protocol; 113 experienced severe AWS. The PRE (n = 75) and POST (n = 38) groups were evenly matched in age, sex, history of AWS, and severity of illness. There was a substantial difference in POST patients who received focused treatment (51.3% vs. 73.7%, p = .03). The POST group had a significant decrease in hospital LOS (14.0 vs. 9.8 days, p = .03) and ICU LOS (7.4 vs. 4.4 days, p = .03).Conclusion: Early, focused management of severe AWS was associated with a decrease in ICU and hospital LOS.

Sodium Oxybate Therapy for Alcohol Withdrawal Syndrome and Keeping of Alcohol Abstinence.

Gamma-hydroxybutyrate (GHB or sodium oxybate) is both an exogenous and endogenous molecule with neuromodulator properties. In the United States, GHB is an approved drug for the treatment of narcolepsy and narcolepsy with cataplexy in adults. In some European Union countries, sodium oxybate is applied for the treatment of opioid and alcohol withdrawal. The aim of the present review was to describe the state of art of the pre-clinical research and the clinical evidence related to GHB used alone or in combination with other treatments in alcohol withdrawal syndrome and alcohol abstinence maintenance. Internationally published pre-clinical findings and clinical studies investigating the effects of GHB on alcohol withdrawal syndrome and alcohol abstinence maintenance were collected and described considering seven clinical studies involving GHB in the treatment of alcohol withdrawal abstinence and five clinical studies involving GHB in the treatment of alcohol abstinence maintenance. Furthermore, GHB pharmacology and characteristics of abuse were briefly detailed. Clinical evidence indicates that GHB is effective in reducing symptoms of alcohol withdrawal syndrome and produces beneficial effects comparable to those of benzodiazepines or chlometiazole. GHB proved effective in increasing alcohol abstinence maintenance and in reducing alcohol craving, but it did not show any influence in relapses of heavy drinkers when given alone. Conversely, it seems to be effective in reducing relapses in alcohol dependent patients when given in combination with naltrexone and escitalopram. Despite this bunch of evidence, studies are still limited and investigations including a larger number of patients are needed. In addition, some safety concerns, such as insufficiency against hallucinations in alcohol withdrawal and potential development of GHB dependence have to be more investigated.

Systematic Review of Acupuncture for the Treatment of Alcohol Withdrawal Syndrome

BackgroundAcupuncture has been used as a potential therapy for alcohol withdrawal syndrome (AWS), but evidence for its effects on this condition is limited.ObjectiveTo assess the effects and safety of acupuncture for AWS.Data sourcesCentral Register of Controlled Trials (CENTRAL), PubMed, Embase, the Cochrane Library, PsycINFO, Chinese Biomedicine Literature (CBM), China National Knowledge Infrastructure (CNKI) and Wan-Fang Database were searched from their inception to August 2016.Study eligibility criteriaRandomised controlled trials (RCTs) of drug plus acupuncture or acupuncture alone for the treatment of AWS were included.Data collection and analysisContinuous data were expressed as mean difference (MD) with 95% confidence intervals (95% CI). Dichotomous data were expressed as risk ratio (RR) with 95% CI.ResultsEleven RCTs with 875 participants were included. In the acute phase, two trials reported no difference between drug plus acupuncture and drug plus sham acupuncture in the reduction of craving for alcohol; however, two positive trials reported that drug plus acupuncture was superior to drug alone in the alleviation of psychological symptoms. In the protracted phase, one trial reported acupuncture was superior to sham acupuncture in reducing the craving for alcohol, one trial reported no difference between acupuncture and drug (disulfiram), and one trial reported acupuncture was superior to sham acupuncture for the alleviation of psychological symptoms. Adverse effects were tolerable and not severe.ConclusionThere was nosignificant difference between acupuncture (plus drug) and sham acupuncture (plus drug) with respect to the primary outcome measure of craving for alcohol among participants with AWS, and no difference in completion rates (pooled results). There was limited evidence from individual trials that acupuncture may reduce alcohol craving in the protracted phase and help alleviate psychological symptoms; however, given concerns about the quantity and quality of included studies, further large-scale and well-conducted RCTs are needed.Protocol registrationPROSPERO CRD42016039862.

Perioperative Management Of Patients With Alcohol Dependence

The review article covers the issues of perioperative management of patients with alcohol dependence. Particular attention is paid to the most common methods of diagnosing alcohol dependence: the collection of anamnesis and the detection of the amount of alcohol consumed, the use of special questionnaires, direct and indirect laboratory criteria, prevention of development and therapy of alcohol withdrawal syndrome and alcoholic delirium, and infectious complications.

A Symptom-Triggered Benzodiazepine Protocol Utilizing SAS and CIWA-Ar Scoring for the Treatment of Alcohol Withdrawal Syndrome in the Critically Ill.

There are limited data on the efficacy of symptom-triggered therapy for alcohol withdrawal syndrome (AWS) in the intensive care unit (ICU). To evaluate the safety and efficacy of a symptom-triggered benzodiazepine protocol utilizing Riker Sedation Agitation Scale (SAS) scoring for the treatment of AWS in the ICU. We performed a before-and-after study in a medical ICU. A protocol incorporating SAS scoring and symptom-triggered benzodiazepine dosing was implemented in place of a protocol that utilized the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale and fixed benzodiazepine dosing. We enrolled 167 patients (135 in the preintervention and 32 in the postintervention group). The median duration of AWS was shorter in the postintervention (5, interquartile range [IQR] = 4-8 days) than in the preintervention group (8, IQR = 5-12 days; P < 0.01). Need for mechanical ventilation (31% vs 57%, P = 0.01), median ICU length of stay (LOS; 4, IQR = 2-7, vs 7, IQR = 4-11 days, P = 0.02), and hospital LOS (9, IQR = 6-13, vs 13, IQR = 9-18 days; P = 0.01) were less in the postintervention group. There was a reduction in mean total benzodiazepine exposure (74 ± 159 vs 450 ± 701 mg lorazepam; P < 0.01) in the postintervention group. A symptom-triggered benzodiazepine protocol utilizing SAS in critically ill patients is associated with a reduction in the duration of AWS treatment, benzodiazepine exposure, need for mechanical ventilation, and ICU and hospital LOS compared with a CIWA-Ar-based protocol using fixed benzodiazepine dosing.

Symptom-triggered benzodiazepine therapy for alcohol withdrawal syndrome in the emergency department: a comparison with the standard fixed dose benzodiazepine regimen

The aim of the study was to compare symptom-triggered and standard benzodiazepine regimens for the treatment of alcohol withdrawal syndrome in an emergency department clinical decision unit. The authors found...

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.

Poor Care, Not Poor Protocols, for Alcohol Withdrawal–Reply–I

Poor Care, Not Poor Protocols, for Alcohol Withdrawal–Reply–I

Symptom-Triggered Therapy for Alcohol Withdrawal Syndrome in Medical Inpatients

To assess the efficacy of symptom-triggered therapy vs usual care for alcohol withdrawal syndrome (AWS) in medical inpatients. This study was a retrospective analysis of patients admitted to general medical services between January 1, 1995, and December 31, 1998, who experienced AWS during the admission. This study was conducted at Saint Marys Hospital, Rochester, Minn. Patients were identified from hospital discharge diagnoses and pharmacy data. Symptom-triggered therapy for AWS was initiated in 1997. Patients were divided into preimplementation (1995-1996) and postimplementation (1997-1998) cohorts. Age, sex, medical comorbid conditions, previous AWS (including seizures and delirium tremens), duration of treatment for AWS, benzodiazepine use and dose, complications of AWS, and adverse outcomes of treatment during the incident admission were abstracted from the medical records of eligible patients. Comorbid conditions were classified according to the Charlson comorbidity index. Differences between the cohorts were assessed with use of logistic regression models and analysis of covariance. Review of medical records from 638 admissions (536 patients) yielded 216 admissions eligible for this study. After adjustment for age, sex, Charlson comorbidity index, previous AWS, previous alcohol withdrawal seizures, and previous delirium tremens, we found no significant difference between cohorts for duration of treatment (P=.16), benzodiazepine use (P=.21), total dose of benzodiazepine (P=.38), or total complication rate (P=.053). We did observe a significant difference in the occurrence of delirium tremens between the 2 treatment groups (P=.04). This was especially apparent for patients with no history of delirium tremens. Symptom-triggered therapy is effective treatment for AWS in medical inpatients. In this retrospective study, it did not result in shorter duration of treatment but was associated with a decreased occurrence of delirium tremens, the most severe and life-threatening complication of AWS. This result was most apparent in patients with no history of delirium tremens.

β-Carbolines in alcohol-dependent intensive care patients during prophylactics and therapy of alcohol withdrawal syndrome.

The primary aim of this study was to investigate whether the naturally occurring beta-carbolines norharman and harman differed between alcohol-dependent patients who developed alcohol withdrawal syndrome (AWS) and those who did not. The secondary aim was to determine whether different treatment regimens influenced the levels of the beta-carbolines. Thirty chronic alcoholics with carcinoma of the upper digestive tract were included in this study. They were prophylactically treated by two different medical regimens: flunitrazepam and clonidine (FNZ regimen) and gamma-hydroxybutyrate and clonidine (GHB regimen). Patients exceeding the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) score of 20 were assigned to the AWS therapy group and received haloperidol in addition to their prevous prophylactic treatment. Patients without AWS remained in the prophylactic group. From days 1-4 of the intensive care unit (ICU) stay norharman, but not harman, was increased in the AWS therapy group. In the FNZ regimen, six of 16 patients (38%) and in the GHB regimen, nine of 14 patients (64%) developed AWS (p= 0.14). Norharman levels did not differ between the two regimens. However, harman levels were increased in the GHB treated regimen on days 1, 2 and 4 following admission to the ICU and correlated with the severity of alcohol withdrawal syndrome. As norharman was elevated in the therapeutically treated ICU patients, this marker appears to be involved in the pathogenesis of AWS. As harman was elevated before and during hallucinations on the GHB regimen, it seems reasonable to carry out further investigations into the potential role of harman as a hallucinatory substance.

Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma

To assess the effect of three different alcohol withdrawal therapy regimens in traumatized chronic alcoholic patients with respect to the duration of mechanical ventilation and the frequency of pneumonia and cardiac disorders during their intensive care unit (ICU) stay. A prospective, randomized, blinded, controlled clinical trial. A university hospital ICU. Multiple-injured alcohol-dependent patients (n=180) transferred to the ICU after admission to the emergency room and operative management. A total of 180 patients were included in the study; however, 21 patients were excluded from the study after assignment. Patients who developed actual alcohol withdrawal syndrome were randomized to one of the following treatment regimens: flunitrazepam/clonidine (n=54); chlormethiazole/haloperidol (n=50); or flunitrazepam/haloperidol (n=55). The need for administration of medication was determined, using a validated measure of the severity of alcohol withdrawal (Revised Clinical Institute Withdrawal Assessment for Alcohol Scale). The duration of mechanical ventilation and major intercurrent complications, such as pneumonia, sepsis, cardiac disorders, bleeding disorders, and death, were documented. Patients did not differ significantly between groups regarding age, Revised Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II score on admission. In all except four patients in the flunitrazepam/clonidine group, who continued to hallucinate, the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale decreased to <20 after initiation of therapy. ICU stay did not significantly differ between groups (p=.1669). However, mechanical ventilation was significantly prolonged in the chlormethiazole/haloperidol group (p=.0315) due to an increased frequency of pneumonia (p=.0414). Cardiac complications were significantly (p=.0047) increased in the flunitrazepam/clonidine group. There was some advantage in the flunitrazepam/clonidine regimen with respect to pneumonia and the necessity for mechanical ventilation. However, four (7%) patients had to be excluded from the study due to ongoing hallucinations during therapy. Also, cardiac complications were increased in this group. Thus, flunitrazepam/haloperidol should be preferred in patients with cardiac or pulmonary risk. Further studies are required to determine which therapy should be considered.