Treatment Of Alcohol Withdrawal Research Articles

Load and go: Assessing safety outcomes of patients discharged from the emergency department after receiving phenobarbital for alcohol withdrawal.

Phenobarbital (PB) is a long-acting GABA A-agonist with favorable pharmacokinetics (long half-life and duration of effect) that allows effective treatment of alcohol withdrawal (AW) after administration of a single loading dose. Current evidence suggests that in the setting of AW, PB administration may be associated with decreased hospital admissions and hospital length of stay. The aim of this study was to evaluate the safety outcomes of AW patients who were treated and discharged from the emergency department (ED) after receiving PB for AW. This retrospective chart review included a convenience sample of 33 AW patients who presented to four EDs within an 18-month span. Descriptive statistics (frequencies and percentages) were used to describe demographics, distribution of resources and referrals, and the safety outcomes of PB administration for low-risk AW patients. Patients were selected for inclusion in consultation with a medical toxicologist, treated with PB, and discharged from the ED. Electronic medical records were utilized to gather information on the patient cohort. All patients were treated with at least a single loading dose of 5‒10mg/kg (ideal body weight) of intravenous or per os PB during their ED stay. Only one patient had an unanticipated event after discharge, which was related to driving against advice. Two additional patients had ED revisits for recurrent alcohol use within 72h, and 16 patients had recurrent alcohol use within 30 days. All 33 patients were provided with resources for linkage to treatment. None required hospital admission. ED PB "load and go" may be a safe, effective AW treatment that could help treat AW, facilitate linkage to specific rehabilitation treatments, and decrease hospital admissions.

Acupuncture and Massage Techniques Combined to Treat Alcohol Withdrawal Syndrome

During the process of alcohol withdrawal, patients may experience withdrawal symptoms such as anxiety, depression, nausea, vomiting, anorexia, headache, chills, sweating, palpitation, poor sleep, tremors, hallucinations and other withdrawal symptoms. Beneficial effects of acupuncture include reducing the need for alcohol, relieving withdrawal symptoms, and increasing energy and relaxation. In this way, the purpose of quitting drinking can be achieved by regulating the balance of yin and yang in the body and the partial prosperity and partial decline of the internal organs. Acupuncture can reduce a patient's need for alcohol, relieve withdrawal symptoms, reduce anxiety, hostility, stress, insomnia and depression, as well as increase energy and relaxation. After patients quit drinking through acupuncture treatment, alcohol withdrawal symptoms are significantly reduced to a tolerable level or even disappear completely. At the same time, massaging Guanchong point can promote the metabolism of water and alcohol in the body, which has a very good sobering effect.

Reply to Letter to the Editor: Eliminating the Benzos: A Benzodiazepine-Sparing Approach to Preventing and Treating Alcohol Withdrawal Syndrome.

Reply to Letter to the Editor: Eliminating the Benzos: A Benzodiazepine-Sparing Approach to Preventing and Treating Alcohol Withdrawal Syndrome.

Impact of a Divided Phenobarbital Load and Taper Compared With Lorazepam Symptom Triggered Therapy in Hospitalized Patients.

Benzodiazepines are the preferred treatment for alcohol withdrawal. Phenobarbital is an alternative in the setting of prescriber expertise or benzodiazepine contraindication. To evaluate the efficacy and safety of a phenobarbital dosing strategy aimed at treating a spectrum of alcohol withdrawal symptoms across various patient populations. Retrospective review of patients admitted with concerns of alcohol withdrawal between May 2018 and November 2022. Patients were separated into a before-after cohort of lorazepam or phenobarbital. The primary outcome was hospital length of stay (LOS). Secondary outcomes were intensive care unit (ICU) LOS, escalation of respiratory support, increased level of care (LOC), and incidence of delirium tremens and/or seizures. Two hundred and seventy-seven patients received lorazepam and 198 received phenobarbital. Hospital LOS was longer in the phenobarbital cohort compared with the lorazepam cohort (6.9 vs 9.3 days). There was no difference in ICU LOS. Level of care increases were fewer in the phenobarbital cohort (4 events vs 19 events). There were higher rates of non-invasive respiratory interventions in the lorazepam cohort and higher rates of mechanical ventilation in the phenobarbital cohort. Utilization of phenobarbital was attributed to a reduction in delirium tremens and seizures. This study is novel because of the broad application of a phenobarbital order set across multiple levels of care and patient admission diagnoses. A risk targeted split load intravenous phenobarbital order set can safely be administered to patients with fewer escalations of care, seizures, delirium tremens, and respiratory care escalation.

Phenobarbital Versus Benzodiazepines for the Treatment of Severe Alcohol Withdrawal.

Phenobarbital may offer advantages over benzodiazepines for severe alcohol withdrawal syndrome (SAWS), but its impact on clinical outcomes has not been fully elucidated. The purpose of this study was to determine the clinical impact of phenobarbital versus benzodiazepines for SAWS. This retrospective cohort study compared phenobarbital to benzodiazepines for the management of SAWS for patients admitted to progressive or intensive care units (ICUs) between July 2018 and July 2022. Patients included had a history of delirium tremens (DT) or seizures, Clinical Institute Withdrawal Assessment of Alcohol-Revised (CIWA-Ar) >15, or Prediction of Alcohol Withdrawal Severity Scale (PAWSS) score ≥4. The primary outcome was hospital length of stay (LOS). Secondary outcomes included progressive or ICU LOS, incidence of adjunctive pharmacotherapy, and incidence/duration of mechanical ventilation. The final analysis included 126 phenobarbital and 98 benzodiazepine encounters. Patients treated with phenobarbital had shorter median hospital LOS versus those treated with benzodiazepines (2.8 vs 4.7 days; P < 0.0001); a finding corroborated by multivariable analysis. The phenobarbital group also had shorter median progressive/ICU LOS (0.7 vs 1.3 days; P < 0.0001), and lower incidence of dexmedetomidine (P < 0.0001) and antipsychotic initiation (P < 0.0001). Fewer patients in the phenobarbital group compared to the benzodiazepine group received new mechanical ventilation (P = 0.045), but median duration was similar (1.2 vs 1.6 days; P = 1.00). Scheduled phenobarbital was associated with decreased hospital LOS compared to benzodiazepines for SAWS. This was the first study to compare outcomes of fixed-dose, nonoverlapping phenobarbital to benzodiazepines in patients with clearly defined SAWS and details a readily implementable protocol.

Response to: "Eliminating the Benzos: A Benzodiazepine-Sparing Approach to Preventing and Treating Alcohol Withdrawal Syndrome".

Response to: "Eliminating the Benzos: A Benzodiazepine-Sparing Approach to Preventing and Treating Alcohol Withdrawal Syndrome".

Phenobarbital treatment of alcohol withdrawal in the emergency department: A systematic review and meta-analysis.

Despite frequent treatment of alcohol withdrawal syndrome (AWS) in the emergency department (ED), evidence for phenobarbital (PB) as an ED alternative therapy is mixed. We conducted a systematic review and meta-analysis comparing safety and efficacy of PB to benzodiazepines (BZDs) for treatment of AWS in the ED. We searched articles and references published in English in PubMed, Web of Science, and Embase from inception through May 2022. We included randomized trials and cohort studies comparing treatment with PB to BZD controls and excluded studies focused on non-AWS conditions. Review was conducted by two blinded investigators and a third author; eight of 59 (13.6%) abstracts met inclusion criteria for review and meta-analysis using a random-effects model. Treatment superiority was evaluated through utilization, pharmacologic, and clinical outcomes. Primary outcomes for meta-analysis were the proportion of patients (1) admitted to the intensive care unit (ICU), (2) admitted to the hospital, (3) readmitted to the ED after discharge, and (4) who experienced adverse events. Eight studies (two randomized controlled trials, six retrospective cohorts) comprised data from 1507 patients in 2012 treatment encounters for AWS. All studies were included in meta-analysis for adverse events, seven for hospital admission, five for ICU admission, and three for readmission to the ED after discharge. Overall methodological quality was low-moderate, risk of bias moderate-high, and statistical heterogeneity moderate. Pooled relative risk of ICU admission for those treated with PB versus BZD was 0.92 (95% confidence interval [CI] 0.54-1.55). Risk for admission to the hospital was 0.98 (95% CI 0.89-1.07) and for any adverse event was 1.1 (95% CI 0.78-1.57); heterogeneity prevented meta-analysis for ED readmission. The current literature base does not show that treatment with PB significantly reduces ICU admissions, hospital admissions, ED readmissions, or adverse events in ED patients with AWS compared with BZDs alone.

Fixed-Dose Phenobarbital Versus As-Needed Benzodiazepines for the Management of Alcohol Withdrawal in Acute Care General Internal Medicine.

The management of patients at risk of severe alcohol withdrawal is challenging because conventional treatment with as-needed benzodiazepines may be ineffective. We created a fixed-dose phenobarbital protocol and compared patient outcomes using this protocol with an as-needed benzodiazepine protocol. Patients admitted from the emergency department (ED) to General Medicine from January 1 to June 30, 2022 and treated for alcohol withdrawal with a novel phenobarbital protocol were compared with all of the patients admitted from the ED to General Medicine from January 1 to June 30, 2018, and treated with as-needed benzodiazepines. The primary outcome was a composite of intensive care unit (ICU) transfer or mortality. Secondary outcomes included mortality, ICU transfer, seizure, length of stay, excess sedation, delirium, against medical advice discharge, 30-day re-admission, 30-day ED reevaluation, and antipsychotic use. There were 54 patients in the phenobarbital group and 197 in the benzodiazepine group. The phenobarbital group was less medically complex but had more risk factors for severe withdrawal. There was no difference in the primary outcome, although there was a trend toward benefit in the phenobarbital group (3.7 vs 8.1%, P = 0.26), and there was a lower incidence of delirium in the phenobarbital cohort (0 vs 8.6%, P = 0.03). Secondary outcome trends favored phenobarbital, with lower mortality, ICU transfer, seizure, oversedation, against medical advice discharge, and 30-day re-admissions. A subgroup analysis accounting for differences in patient populations in the primary analysis found similar results. Phenobarbital is as safe and effective as benzodiazepine-based protocols for the treatment of high-risk alcohol withdrawal, with lower rates of delirium.

A Retrospective Evaluation of Adjunctive Phenobarbital vs. Benzodiazepine Alone for the Treatment of Moderate Alcohol Withdrawal in the Emergency Department

BackgroundPhenobarbital has been used in the emergency department (ED) as both a primary and adjunctive medication for alcohol withdrawal, but previous studies evaluating its impact on patient outcomes are limited by heterogenous symptom severity. ObjectivesWe compared the clinical outcomes of ED patients with moderate alcohol withdrawal who received phenobarbital, with or without benzodiazepines, with patients who received benzodiazepine treatment alone. MethodsThis is a retrospective cohort study conducted at a single academic medical center utilizing chart review of ED patients with moderate alcohol withdrawal between 2015 and 2020. Patient encounters were classified into two treatment categories based on medication treatment: phenobarbital alone or in combination with benzodiazepines vs. benzodiazepines alone. Chi-square test or Fisher's exact was used to analyze categorical variables and the Student's t-test for continuous data. ResultsAmong the 287 encounters that met inclusion criteria, 100 received phenobarbital, compared with 187 that received benzodiazepines alone. Patients who received phenobarbital were provided significantly more lorazepam equivalents. There was a significant difference in the percentage of patient encounters that required admission to the hospital in the phenobarbital cohort compared with the benzodiazepine cohort (75% vs. 43.3%, p < 0.001). However, there was no difference in admission level of care to the floor (51.2% vs. 52.0%), stepdown (33.8% vs. 28%), or intensive care unit (15% vs. 20%), respectively. ConclusionsPatients who received phenobarbital for moderate alcohol withdrawal were more likely to be admitted to the hospital, but there was no difference in admission level of care when compared with patients who received benzodiazepines alone. Patients who received phenobarbital were provided greater lorazepam equivalents in the ED.

Concurrent opioid and alcohol withdrawal management.

Concurrent alcohol and opioid withdrawal syndrome is a common and challenging clinical scenario with little published evidence or guidance to inform pharmacotherapy strategies. Concurrent use of benzodiazepines and opioid agonists, which are considered first-line agents for management of each withdrawal syndrome independently, is controversial and often avoided in clinical practice. Strategies to provide effective, simultaneous medication treatment of alcohol and opioid withdrawal while optimizing patient safety are demonstrated through 3 patient cases.

Factorial, Construct, and Predictive Validity of the Motivation for Treatment Scale in Alcohol-Use Disorder Withdrawal Treatment

Introduction: The aim of the present study was to examine for the first time the factorial, construct, and predictive validity of the motivation for treatment (MfT) scale in a cohort of patients undergoing inpatient-qualified alcohol withdrawal treatment with the goal of referring patients to further treatment. The MfT scale has previously been evaluated in different settings of substance abuse treatment, revealing factorial ambiguity. To the best of our knowledge, the present study is the first study that conducted comprehensive factor analyses versus separate analyses of the factors conducted in prior studies in order to clarify the aforementioned factorial ambiguity. Methods: A total of 249 patients (mean age 45.2 years (SD = 10.3); 34.4% females) with alcohol dependence were assessed. Data were obtained from four inpatient clinics specialized in qualified alcohol withdrawal treatment in Germany. First, confirmatory factor analyses were carried out to examine the fit of the four models discussed in the literature. Second, an exploratory factor analysis was conducted. Correlations of the new factors with other motivational constructs and referral to a subsequent treatment were investigated as measures of construct and predictive validity. Results: None of the four models showed an acceptable fit to the data in confirmatory analyses. The exploratory analysis suggested to eliminate seven items because of inappropriate factor loadings and resulted in a shortened MfT scale, which consists of three factors based on 17 items. For the latent variables “problem recognition,” “desire for help,” and “treatment readiness,” satisfactory composite reliability was found with 0.82, 0.80, and 0.78, respectively. Evidence for predictive validity was found in the correlation between “treatment readiness” and referral to a subsequent treatment. Discussion/Conclusion: The new shortened MfT scale exhibited remarkable parsimony, which is desirable in settings such as withdrawal treatment, where patients frequently are cognitively or physically impaired. Despite its briefness, construct and predictive validity were better than in the original version of the MfT scale. The factorial validity of the suggested scale needs to be corroborated in further research.

Establishing the safety of phenobarbital treatment of alcohol withdrawal syndrome on general medical wards: A retrospective cohort study

IntroductionConcern about adverse effects from phenobarbital limits its use in treating alcohol withdrawal syndrome (AWS) on general medical wards. Benzodiazepines are the recommended treatment for inpatient management of AWS, yet a subset of patients have an inadequate response or experience complications of AWS despite treatment with benzodiazepines. Data supporting an alternative treatment are needed. We set out to estimate the rate of serious adverse events (SAEs) of phenobarbital treatment for AWS on general medical wards. MethodsRetrospective cohort study of all general medical ward patients hospitalized at a single tertiary urban VA Medical Center from October 2018–May 2021 who received phenobarbital for treatment of AWS. Primary outcomes were SAEs attributed to phenobarbital and treatment failure. SAEs were defined as ICU transfer or intubation for over-sedation, pneumonia, and death. Treatment failure was defined as progression of withdrawal resulting in seizure, ICU transfer, behavioral emergencies, or death. ResultsDuring the study period, phenobarbital was administered in 29% (244) of all AWS hospitalizations. Among them, 93% had a history of AWS hospitalization and 68% had a history of complicated AWS. Fifty-three percent of patients met criteria for moderate, severe, or complicated withdrawal prior to phenobarbital initiation. The mean cumulative dose of phenobarbital per patient was 966.5 mg (13.6 mg/kg). SAEs occurred in 1 of 244 hospitalizations (0.4%): there were no intubations, ICU transfers for oversedation, or deaths due to phenobarbital or AWS. One case of pneumonia was possibly attributable to phenobarbital. Treatment failures (6 ICU transfers, 9 behavioral emergencies) were identified during 12 of 244 hospitalizations (4.9%). ConclusionsSAEs and treatment failures were infrequent among 148 patients treated with phenobarbital across 244 hospitalizations with a mean cumulative dose of 966.5 mg per patient. Our findings suggest that phenobarbital is a safe alternative treatment of AWS in general medical ward patients.

Eliminating the benzos: A benzodiazepine-sparing approach to preventing and treating alcohol withdrawal syndrome.

Alcohol withdrawal syndrome (AWS) represents significant cost to the hospitalized trauma population from a clinical and financial perspective. Historically, AWS has been managed with benzodiazepines. Despite their efficacy, benzodiazepines carry a heavy adverse effect profile. Recently, benzodiazepine-sparing protocols for the prophylaxis and treatment of AWS have been used in medical patient populations. Most existing benzodiazepine-sparing protocols use phenobarbital, while ours primarily uses gabapentin and clonidine, and no such protocol has been developed and examined for safety and efficacy specifically within a trauma population. In December of 2019, we implemented our benzodiazepine-sparing protocol for trauma patients identified at risk for alcohol withdrawal on admission. Trauma patients at risk for AWS admitted to an academic Level 1 trauma center before (conventional) and after (benzodiazepine-sparing [BS]) protocol implementation were compared. Outcomes examined include morphine milligram equivalent dosing rates and lorazepam equivalent dosing rates as well as the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) scores, hospital length of stay, intensive care unit length of stay, and ventilator days. A total of 387 conventional and 134 benzodiazepine sparing patients were compared. Injury Severity Score (13 vs. 16, p = 0.10) and admission alcohol levels (99 vs. 149, p = 0.06) were similar. Patients in the BS pathway had a lower maximum daily CIWA-Ar (2.7 vs. 1.5, p = 0.04). While mean morphine milligram equivalent per day was not different between groups (31.5 vs. 33.6, p = 0.49), mean lorazepam equivalents per day was significantly lower in the BS group (1.1 vs. 0.2, p < 0.01). Length of stay and vent days were not different between the groups. Implementation of a benzodiazepine-sparing pathway that uses primarily clonidine and gabapentin to prevent and treat alcohol withdrawal syndrome in trauma patients is safe, reduces the daily maximum CIWA-Ar, and significantly decreases the need for benzodiazepines. Future studies will focus on outcomes affected by avoiding AWS and benzodiazepines in the trauma population. Therapeutic/Care Management; Level IV.

A Comparison of Injectable Diazepam and Lorazepam in the Goal-Directed Management of Severe Alcohol Withdrawal.

Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies. The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS). Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment. A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01). DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability.

The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene-environment interaction in mood disorders.

Alcohol use disorder (AUD) is a common mental disorder characterized by repeated withdrawal episodes. Negative emotions during withdrawal are the primary factors affecting successful abstinence. Oxytocin is a critical modulator of emotions. OXTR, the oxytocin receptor, may also be a promising candidate for treating alcohol withdrawal symptoms. Previous studies indicated that people with different genotypes of OXTR rs2254298 were reported to suffer from more significant depressive or heightened anxiety symptoms when experiencing early adversity. The present study aims to explore the modulatory role of the polymorphism OXTR rs2254298 on mood disorders during alcohol withdrawal and to help researchers better understand and develop effective relapse prevention and interventions for alcohol use disorders. We recruited 265 adult Chinese Han men with AUD. Anxiety and depressive symptoms were measured using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Alcohol dependence levels were measured using Michigan Alcoholism Screening Test. Genomic DNA extraction and genotyping from participants' peripheral blood samples. First, a multiple linear regression was used to set the alcohol dependence level, OXTR.rs2254298, interaction terms as the primary predictor variable, and depression or anxiety as an outcome; age and educational years were covariates. There was a significant interaction between OXTR rs2254298 and alcohol dependence level on anxiety (B = 0.23, 95% confidence interval [CI]: 0.01-0.45) but not on depression (B = -0.06, 95% CI: -0.30 - 0.18). The significance region test showed that alcohol-dependent men who are GG homozygous were more likely to experience anxiety symptoms than subjects with the A allele (A allele: β = 0.27, p < 0.001; GG homozygote: β = 0.50, p < 0.001). Finally, re-parameterized regression analysis demonstrated that this gene-environment interaction of OXTR rs2254298 and alcohol dependence on anxiety fits the weak differential susceptibility model (R2 = 0.17, F (5,259) = 13.46, p < 0.001). This study reveals a gene-environment interactive effect between OXTR rs2254298 and alcohol withdrawal on anxiety but not depression. From the perspective of gene-environment interactions, this interaction fits the differential susceptibility model; OXTR rs2254298 GG homozygote carriers are susceptible to the environment and are likely to experience anxiety symptoms of alcohol withdrawal.

Digitally Assisted Peer Recovery Coach to Facilitate Linkage to Outpatient Treatment Following Inpatient Alcohol Withdrawal Treatment: Proof-of-Concept Pilot Study.

Alcohol use disorder (AUD), associated with significant morbidity and mortality, continues to be a major public health problem. The COVID-19 pandemic exacerbated the impact of AUD, with a 25% increase in alcohol-related mortality from 2019 to 2020. Thus, innovative treatments for AUD are urgently needed. While inpatient alcohol withdrawal management (detoxification) is often an entry point for recovery, most do not successfully link to ongoing treatment. Transitions between inpatient and outpatient treatment pose many challenges to successful treatment continuation. Peer recovery coaches-individuals with the lived experience of recovery who obtain training to be coaches-are increasingly used to assist individuals with AUD and may provide a degree of continuity during this transition. We aimed to evaluate the feasibility of using an existing care coordination app (Lifeguard) to assist peer recovery coaches in supporting patients after discharge and facilitating linkage to care. This study was conducted on an American Society of Addiction Medicine-Level IV inpatient withdrawal management unit within an academic medical center in Boston, MA. After providing informed consent, participants were contacted by the coach through the app, and after discharge, received daily prompts to complete a modified version of the brief addiction monitor (BAM). The BAM inquired about alcohol use, risky, and protective factors. The coach sent daily motivational texts and appointment reminders and checked in if BAM responses were concerning. Postdischarge follow-up continued for 30 days. The following feasibility outcomes were evaluated: (1) proportion of participants engaging with the coach before discharge, (2) proportion of participants and the number of days engaging with the coach after discharge, (3) proportion of participants and the number of days responding to BAM prompts, and (4) proportion of participants successfully linking with addiction treatment by 30-day follow-up. All 10 participants were men, averaged 50.5 years old, and were mostly White (n=6), non-Hispanic (n=9), and single (n=8). Overall, 8 participants successfully engaged with the coach prior to discharge. Following discharge, 6 participants continued to engage with the coach, doing so on an average of 5.3 days (SD 7.3, range 0-20 days); 5 participants responded to the BAM prompts during the follow-up, doing so on an average of 4.6 days (SD 6.9, range 0-21 days). Half (n=5) successfully linked with ongoing addiction treatment during the follow-up. The participants who engaged with the coach post discharge, compared to those who did not, were significantly more likely to link with treatment (83% vs 0%, χ2=6.67, P=.01). The results demonstrated that a digitally assisted peer recovery coach may be feasible in facilitating linkage to care following discharge from inpatient withdrawal management treatment. Further research is warranted to evaluate the potential role for peer recovery coaches in improving postdischarge outcomes. ClinicalTrials.gov NCT05393544; https://www.clinicaltrials.gov/ct2/show/NCT05393544.

Alcohol perturbed locomotor behavior, metabolism, and pharmacokinetics of gamma-hydroxybutyric acid in rats

Gamma-hydroxybutyric acid (GHB), both a metabolic precursor and product of gamma-aminobutyric acid (GABA), is a central nervous system depressant used for the treatment of narcolepsy-associated cataplexy and alcohol withdrawal. However, administration of GHB with alcohol (ethanol) is a major cause of hospitalizations related to GHB intoxication. In this study, we investigated locomotor behavior as well as metabolic and pharmacokinetic interactions following co-administration of GHB and ethanol in rats. The locomotor behavior of rats was evaluated following the intraperitoneal administration of GHB (sodium salt, 500 mg/kg) and/or ethanol (2 g/kg). Further, time-course urinary metabolic profiling of GHB and its biomarker metabolites glutamic acid, GABA, succinic acid, 2,4-dihydroxybutyric acid (OH-BA), 3,4-OH-BA, and glycolic acid as well as pharmacokinetic analysis were performed. GHB/ethanol co-administration significantly reduced locomotor activity, compared to the individual administration of GHB or ethanol. The urinary and plasma concentrations of GHB and other target compounds, except for 2,4-OH-BA, were significantly higher in the GHB/ethanol co-administration group than the group administered only GHB. The pharmacokinetic analysis results showed that the co-administration of GHB and ethanol significantly increased the half-life of GHB while the total clearance decreased. Moreover, a comparison of the metabolite-to-parent drug area under the curve ratios demonstrated that the metabolic pathways of GHB, such α- and β-oxidation, were inhibited by ethanol. Consequently, the co-administration of GHB and ethanol aggravated the metabolism and elimination of GHB and enhanced its sedative effect. These findings will contribute to clinical interpretation of GHB intoxication.

Risk of prolonged sedation with the use of chlordiazepoxide in alcohol withdrawal treatment

Summary The use of chlordiazepoxide in the treatment of alcohol withdrawal symptoms poses a risk of prolonged sedation with the need of weeks lasting antidote treatment, and extended hospitalization due to active metabolites with very long half-lives. We present four case stories to elucidate this issue. One patient received 800 mg chlordiazepoxide and was treated with flumazenil for 42 days. Another patient was treated with 100 mg chlordiazepoxide. 5 days after administration of chlordiazepoxide, concentrations of chlordiazepoxide and its active metabolite demoxepam, were within therapeutic range, the patient was treated with flumazenil for 6 days. He died after palliative care. The great individual variation in the clinical effect of chlordiazepoxide depends on the activity of the CYP P450 system, especially CYP3A4/A5 and CYPS2C19, which can be impaired in cirrhotic and elderly patients.

520 Use of Phenobarbital for Alcohol Withdrawal in Small Burn Patients: Evaluation of a Pilot Protocol

Abstract Introduction Phenobarbital is a long-acting barbiturate that has primarily been used an antiepileptic in clinical practice. However its use as a sedative has seen a resurgence recently especially for the prevention and/or treatment of alcohol withdrawal. It has several characteristics that make it appealing for this indication, including its long half-life and its distinct binding to GABAA receptors that, unlike benzodiazepines, does not depend on endogenous GABA to produce its effects. Several recent studies have evaluated its use for the treatment of alcohol withdrawal both inside and outside of the ICU setting, however reports of its use in patients with burn injury are sparse. A pilot treatment protocol utilizing phenobarbital for patients with less than 20% TBSA burns at high risk of alcohol withdrawal was formulated and put into practice at our center in January of 2022. We sought to evaluate the safety and efficacy of this protocol for quality improvement. Methods This was a retrospective chart review of patients admitted from January to August 2022 with less than 20% TBSA burns who received treatment with phenobarbital for alcohol withdrawal at a major burn center in North Central Florida. There were no exclusion criteria. This project was registered as a Quality Improvement Project with the institution. Results Ten patients were included in the evaluation. Median age was 63 yo, 90% were male, and 70% were Caucasian. Median % TBSA burn was 6.5% (range 0.5-12%) and median length of stay was 16 days (range 9-50 days). Most patients were injured by Fire/Flame (80%). Most patients had a history of binge drinking (70%), and most reported drinking at least 3-4 alcoholic drinks 4 or more times per week (70%). Of those that had a detectable blood alcohol concentration on admission, the median was 163 mg/dL (range 44-325 mcg/dL). Over half of the patients (60%) received an IV bolus (either 5 or 10 mg/kg based on ideal body weight) of phenobarbital followed by an oral taper, with the remaining 40% having received an oral taper without a bolus dose. Median RASS prior to initiation of the protocol was +1, and the majority of patients remained RASS +1 or less throughout the duration of the protocol (70%). No rescue benzodiazepines were needed, no seizures were identified, and no intubations occurred while patients were on the protocol. Conclusions The phenobarbital protocol was well tolerated and controlled agitation in the majority of the patients who received it. No obvious safety concerns were identified during this review. Although this was a small sample size, these results are encouraging and support continued use of phenobarbital in preventing and controlling symptoms of alcohol withdrawal in patients with less than 20% TBSA burns. Applicability of Research to Practice Phenobarbital may be a safe and effective benzodiazepine-free option for preventing and/or treating alcohol withdrawal in small burn patients.

POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME ASSOCIATED WITH ALCOHOL WITHDRAWAL

Posterior reversible encephalpathy is a neurological condition with clinico- radiological- diagnosis characterized with headache, confusion, seizure, visual disturbance.Clinical and imaging characteristics are usually reversible. 24 year old male patient with a history of consumption of alcohol, last drink 1 day back, presented to department with one episode of seizure,on day 2 complain of loss of vision with BP:166/102 mmhg PR = 114 bpm and other neurological examinations are within the normal limit. Non contrast MRI shows diffuse oedema noted in the bilateral cerebral hemispheres predominantly in the bilateral occipital lobes continued alcohol withdrawal treatment and started on antihypertensive medication improved well and discharged on day 9. Posterior reversible encephalpathy is the clinico- radiological- diagnosis with exact pathophysiology of PRES in alcohol withdrawal is still not clear, treatment is symptomatic with use of antihypertensive