Severe Alcohol Withdrawal Syndrome Research Articles

Characterization of alcohol-related seizures in withdrawal syndrome.

Alcohol-related seizures (ARS) are one of the most important consequences of alcohol withdrawal syndrome (AWS). However, demographic and clinical characteristics, and furthermore, the relationship of ARS with delirium tremens (DT), have not yet been evaluated in detail. Therefore, the aim of the present study was to reveal the correlates of ARS and examine the interaction of ARS with the occurrence of DT and with the severity of AWS. In the retrospective study (Study 1) 2851 medical charts of inpatient admissions characterized by AWS and DT were listed. Demographic and clinical variables of ARS were assessed. In the follow-up study (Study 2), patients admitted with AWS without (N = 28) and with (N = 18) ARS were enrolled. Study 1 was performed between 2008 and 2023, and Study 2 was performed in 2019 in Hungary. To determine the severity of AWS, the Clinical Institute Withdrawal Assessment Scale for Alcohol, Revised (CIWA-Ar) was used. ARS is a provoked, occasional seizure; therefore, patients with epilepsy syndrome were excluded from the two studies. Statistical analyses were performed by the means of chi-square tests, multinomial logistic regressions, mixed ANOVA, and derivation. The occurrence of DT, the history of ARS, and somatic co-morbidities were found to be risk factors for the appearance of ARS. ARS was proved to be a risk factor for the development of DT. In the follow-up study, there was no difference in the decrease of CIWA-Ar scores between the groups. Our present findings support the likelihood of kindling, which is one of the most important mechanisms underlying the development of ARS, but do not directly prove its presence. Additionally, our results revealed that the severity of AWS is not influenced by the presence of ARS. Provoked, occasional seizures during AWS are defined as ARS. In the present study, predictors and interactions of these seizures with DT-the most severe form of withdrawal-and with the severity of withdrawal were examined in retrospective and follow-up studies. The present study shows that a history of withdrawal seizures, the occurrence of DT, and somatic comorbidities are predictors of the development of seizures. Furthermore, our findings suggest that the presence of seizures does not influence the severity of withdrawal.

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.

ZSCAN25 methylation predicts seizures and severe alcohol withdrawal syndrome

ABSTRACT Currently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to hospitals for consideration of withdrawal syndrome (AWS). However, only a fraction of those admitted will experience severe AWS. Previously, we and others have shown that epigenetic indices, such as the Alcohol T-Score (ATS), can quantify recent alcohol consumption. However, whether these or other alcohol biomarkers, such as carbohydrate deficient transferrin (CDT), could identify those at risk for severe AWS is unknown. To determine this, we first conducted genome-wide DNA methylation analyses of subjects entering and exiting alcohol treatment to identify loci whose methylation quickly reverted as a function of abstinence. We then tested whether methylation at a rapidly reverting locus, cg07375256, or other existing metrics including PAWSS scores, CDT levels, or ATS, could predict outcome in 125 subjects admitted for consideration of AWS. We found that PAWSS did not significantly predict severe AWS nor seizures. However, methylation at cg07375256 (ZSCAN25) and CDT strongly predicted severe AWS with ATS (p < 0.007) and cg07375256 (p < 6 × 10–5) methylation also predicting AWS associated seizures. We conclude that epigenetic methods can predict those likely to experience severe AWS and that the use of these or similar Precision Epigenetic approaches could better guide AWS management.

Does phenobarbital reduce the hospital length of stay for patients suffering from severe alcohol withdrawal? A retrospective comparison of phenobarbital to lorazepam infusions

IntroductionData suggest that phenobarbital is as effective as benzodiazepines at managing withdrawal via its direct activation of the gamma-aminobutyric acid receptor and modulating glutamate-mediated stimulation of the N-methyl-D-aspartate receptor. There are little data evaluating the effect of phenobarbital on severe withdrawal syndromes. ObjectiveThe purpose of this study was to evaluate the effect of phenobarbital compared with protocolized, symptom-driven, benzodiazepine administration on hospital length of stay (LOS) in patients experiencing severe withdrawal. MethodsThis is a retrospective chart review of patients evaluated in the emergency department for the treatment of severe alcohol withdrawal syndrome, defined as a Clinical Institute Withdrawal Assessment for Alcohol – Revised score of 20 or greater during their visit. The primary outcome measure was the difference in hospital LOS between those receiving phenobarbital and those receiving continuous lorazepam infusions. Secondary outcomes include intensive care unit (ICU) admission, ICU LOS, need for mechanical ventilation, and incidence of oversedation. ResultsIn all, 298 patients met inclusion, with 131 treated with phenobarbital and 167 initiated on a lorazepam infusion. Hospital LOS was found to be statistically significantly greater in the lorazepam infusion cohort (7.6 ± 5.3 vs. 5.2 ± 4.5 days, P < 0.001) than the phenobarbital cohort. Patients treated with lorazepam were found to have increased admissions to the ICU (risk ratio [RR] 1.79 [95% CI 1.27–2.92]) and higher rates of oversedation (RR 1.71 [95% CI 2.09–4.25]). There were no differences in ICU LOS and need for mechanical ventilation. ConclusionData from this study suggest that phenobarbital may be associated with a decrease in hospital LOS in severe alcohol withdrawal and should be considered as an alternative to benzodiazepine infusions in these patients.

Predictors of Escalation to Intensive Care Unit Level of Care Among Admissions for Alcohol Withdrawal.

According to the 2019 National Survey on Drug Use and Health, 14.5 million people ages 12 and older had alcohol abuse disorder. Alcohol withdrawal syndrome (AWS) can be defined as a collection of physical symptoms experienced due to abrupt cessation of alcohol after long-term dependence. In instances where regular inpatient management fails to control AWS symptoms, patients are shifted to intensive care units (ICUs) for closer monitoring and prevention of life-threatening complications like withdrawal seizures and delirium tremens (DTs), labeled as severe alcohol withdrawal syndrome (SAWS). Although this represents a significant healthcare burden, minimal studies have been conducted to determine objective predictors. In this study, we aim to determine the effect of patient demographics, socio-economic status, biochemical parameters, and clinical factors on the need for escalation to ICU level of care among admissions for AWS. Our study showed that factors such as a history of DTs or alcohol-related seizures, the initial protocol of management, degree of reported alcohol usage, activation of rapid response teams, mean corpuscular value, alcohol level on admission, highest Clinical Institute Withdrawal Assessment Alcohol Revised (CIWA-Ar) scored during the hospital stay, and the total amount of sedatives used were significantly associated with escalation to ICU level of care. Clinicians must use these objective parameters to identify high-risk patients and intervene early. We encourage further studies to establish a scoring algorithm incorporating biochemical parameters to tailor management algorithms that might better suit high-risk patients.

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.

Which assessment tools are most useful for identifying hospitalized patients at risk of developing severe alcohol withdrawal syndrome?

Which assessment tools are most useful for identifying hospitalized patients at risk of developing severe alcohol withdrawal syndrome?

Clinical Impact of the CYP2C19 Gene on Diazepam for the Management of Alcohol Withdrawal Syndrome.

Diazepam is a benzodiazepine widely prescribed for the management of patients with severe alcohol withdrawal syndrome to prevent agitation, withdrawal seizures, and delirium tremens. Despite standard dosing of diazepam, a subset of patients experience refractory withdrawal syndromes or adverse drug reactions, such as impaired motor coordination, dizziness, and slurred speech. The CYP2C19 and CYP3A4 enzymes play a key role in the biotransformation of diazepam. Given the highly polymorphic nature of the CYP2C19 gene, we reviewed the clinical impact of variants in the CYP2C19 gene on both the pharmacokinetics of diazepam and treatment outcomes related to the management of alcohol withdrawal syndrome.

Alcohol Biomarker Phosphatidylethanol as a Predictor of the Severity of Alcohol Withdrawal Syndrome.

to investigate the relationship between phosphatidylethanol (PEth) and withdrawal severity in patients with alcohol use disorder (AUD). in 34 patients with AUD admitted for treatment of acute alcohol withdrawal, data were available for initial blood PEth concentrations and scores throughout detoxification of symptoms of withdrawal assessed by trained medical staff using the alcohol withdrawal syndrome (AWS)-scale, a validated scale consisting of 11 items in the alcohol withdrawal syndrome (two subscales with seven physiological and five psychological symptoms). a significant positive correlation between PEth and the severity of alcohol withdrawal was found. When the sample was divided into two groups, according to whether or not AWS score at some point in the treatment reached 6 or more, the median PEth score was higher in those whose peak score had been 6 or more (score of 6 being the suggested cutoff to start medicating the withdrawal syndrome). Although there was a trend for some aspects of the clinical history to be more 'severe' in those with higher AWS, no differences reached significance. blood PEth on admission could have a role in identifying patients at risk of more severe AWS.

786: IMPACT OF FRONT-LOADING PHENOBARBITAL CUMULATIVE DOSE AND ICU ADMISSION FOR ALCOHOL WITHDRAWAL

Introduction: Alcohol withdrawal syndrome is a common reason for hospitalization and progression to severe alcohol withdrawal is associated with ICU admission. Recent evidence suggests symptom triggered use of phenobarbital in the ED is associated with reductions in ICU admission, duration of mechanical ventilation, and hospital length of stay. The objective of our study is to identify if larger cumulative phenobarbital doses in the ED are associated with ICU admission in the absence of strict ICU admission criteria (e.g. mechanical ventilation, hemodynamically unstable). Methods: This was a single center, retrospective analysis of patients with alcohol withdrawal, given symptom triggered doses of phenobarbital in the ED, and subsequently admitted to ICU or non-ICU care areas. We compared cumulative doses of phenobarbital administered in the ED and if higher doses were associated with ICU admission. Secondary outcomes included occurrence of seizure and hospital length of stay. Risk factors for ICU admission were assessed in univariate analyses and multivariable modeling. Results: 200 patients were included (100 ICU and 100 non-ICU) in the study. There was no significant difference in cumulative phenobarbital doses received in the ED between patients admitted to ICU or non-ICU areas (811 mg vs. 780 mg, p=0.6). Secondary outcomes were similar between the groups except a longer hospital length of stay in the ICU group (5.4 days vs 3.6 days, p=0.04). Multivariable analysis identified higher average ED symptom triggered alcohol withdrawal scores (SEWS, aOR 1.44, 95% CI 1.26-1.64, p< 0.0001) and positive blood alcohol concentration on admission (aOR 2.01, 95% CI 1.04-3.89, p=0.04) as predictors of ICU admission. Conclusions: There was no difference in cumulative phenobarbital requirements in patients who were admitted to ICU or non-ICU areas for alcohol withdrawal. Additional risk factors such as higher alcohol withdrawal score and positive blood alcohol concentration may be predictors of more severe withdrawal needing ICU level of care. Additional prospective studies are needed to identify predictors of severe alcohol withdrawal syndrome.

Correlation Between and Nursing Satisfaction With CIWA-Ar, mMINDS, and SEWS Scoring Tools for the Assessment of Severe Alcohol Withdrawal Syndrome in ICU Patients.

Management of alcohol withdrawal syndrome (AWS) requires bedside assessments of symptom severity to guide therapies. Commonly used assessment tools are the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), the modified Minnesota Detoxification Scale (mMINDS) and the Severity of Ethanol Withdrawal Scale (SEWS). To determine strength of correlation between the CIWA-Ar, mMINDS, and SEWS for bedside assessment of severe AWS and to survey nurses regarding ease of use of each tool. A single-center prospective correlation study of the three assessment tools performed by bedside nurses on patients with AWS followed by a questionnaire assessing ease of use of each tool (1 being the easiest and 9 being the hardest). A total of 66 correlation assessments were performed by 49 nurses in 21 patients with AWS. Bedside CIWA-Ar, mMINDS, and SEWS were 14 ± 8.3, 13.9 ± 6.5, and 10.1 ± 4.5, respectively. The Pearson correlation coefficients were 0.814 (95% CI, 0.714-0.881) between CIWA-Ar and mMINDS; 0.722 (95% CI, 0.585-0.820) between CIWA-Ar and SEWS; and 0.658 (95% CI, 0.498-0.775) between SEWS and mMINDS. Nurse ratings for ease of use were 4 ± 2.3 for CIWA-Ar, 2.9 ± 2 for mMINDS (p=0.0044 vs. CIWA-Ar), and 4.8 ± 2.1 for SEWS (p=0.036 vs. CIWA-Ar, p<0.0001 vs. mMINDS). Forty-six (69.7%) respondents preferred mMINDS versus 14 (21.2%) and 6 (9.1%) respondents favored CIWA-Ar and SEWS, respectively. Correlations between the three scoring tools in severe AWS are robust. Only mMINDS was considered easy to use by nurses. It was the preferred tool.

Front-Loaded Versus Low-Intermittent Phenobarbital Dosing for Benzodiazepine-Resistant Severe Alcohol Withdrawal Syndrome.

Phenobarbital is frequently used to manage severe alcohol withdrawal. The purpose of this study was to compare the incidence of mechanical ventilation in patients with benzodiazepine-resistant alcohol withdrawal between front-loaded and low-intermittent phenobarbital dosing strategies. In this retrospective before-after study, we analyzed patients that received phenobarbital for severe alcohol withdrawal syndrome in a tertiary medical ICU. Patients received low-intermittent phenobarbital doses (260mg intravenous push × 1 followed by 130mg intravenous push every 15min as needed) from January2013 to July 2015, and front-loaded phenobarbital doses (10mg/kg intravenous infusion over 30min) from July 2015 to January 2017. In total, 87 patients met inclusion criteria for this study:41received low-intermittentphenobarbital and 46 receivedfront-loadedphenobarbital). The incidence of mechanical ventilation was 13 (28%) in the front-loaded dosing group vs. 26 (63%) in the low-intermittent dosing group (odds ratio 4.4 [95% CI 1.8-10.9]). The cumulative dose of phenobarbital administered and serum phenobarbital levels were similar between both groups, although the front-loaded group had significantly lower benzodiazepine requirements than the low-intermittent group (median 86mg [IQR 24-197] vs. 228mg [115-298], P < 0.01) and reduced need for any continuous sedative infusion (OR 7.7 [95% CI 1.6-27], P < 0.01). There was no difference in respiratory failure or hypotension. Front-loaded phenobarbital dosing, when compared to low-intermittent phenobarbital dosing, for benzodiazepine-resistant alcohol withdrawal was associated with significantly lower mechanical ventilation incidence and continuous sedative use.

Pneumonia is a common and early complication of the Severe Alcohol Withdrawal Syndrome (SAWS)

BackgroundPneumonia (PNA) may complicate the Severe Alcohol Withdrawal Syndrome (SAWS), with ICU admission, mechanical ventilation (MV), prolonged length of stay (LOS), and adverse events. ObjectivesTo examine the onset, features and courses of PNA in patients with SAWS to aid management. MethodsA 33 month contiguous review of SAWS and PNA was conducted at an urban public hospital. ResultsThere were 279 episodes of Alcohol Withdrawal Syndrome (AWS) among 255 patients. Males predominated (91%) with a mean age of 45.8 years (range 23-73), of whom 31% (87/279) developed SAWS with ICU management. Direct ICU admission occurred for 62 patients; 25 were transferred for delirium, seizures, escalating sedation, PNA or other complications. PNA was identified for 34 ICU direct admissions and 13 ward patients. Ten transfers to the ICU also developed PNA for an ICU total of 44/87 (51%), of whom 82% (36/44) required MV. Another 10 ICU patients without PNA received MV for high dose sedation or respiratory failure. Most ICU patients (72/87 (83%)), including all with MV, required IV infusion of sedation. MV prolonged LOS, but LOS for PNA with MV was similar to all MV. ICU transfers had longer LOS with greater use of MV than direct admits (p<0.05). PNA was identified before ICU admission or transfer for 73% (32/44 (p<0.05)), and usually before intubation. Most PNA was Community Acquired Pneumonia (CAP) with P. Pneumoniae frequently cultured. ConclusionsPNA with SAWS is predominately CAP and occurs early. Focused ICU admission with respiratory support are priorities of initial management.

Pharmacological Treatment of Alcohol Withdrawal

Excessive chronic alcohol users, and particularly patients with alcohol use disorder, may present an alcohol withdrawal syndrome if they abruptly stop drinking. Alcohol withdrawal syndrome requires pharmacological treatment for the treatment of withdrawal symptoms and to prevent withdrawal complications. Medically assisted withdrawal treatment is used in alcohol treatment units, but it is also frequently required in patients admitted to hospital for other conditions. Review of major guidelines covering treatment of withdrawal syndrome with the aim to describe recent evidence and recommendations about the pharmacological treatment for alcohol withdrawal syndrome. Four major guidelines concerning treatment of withdrawal syndrome were selected (National Institute for Health and Care Excellence, American Society of Addiction Medicine, World Federation of Societies of Biological Psychiatry and American Psychiatric Association) and screened for the recommendations and level of evidence on drug prescribing for alcohol withdrawal syndrome. The Maudsley guidelines were also considered in this review. All the four reviewed guidelines recommended benzodiazepines as the first line treatment for alcohol withdrawal syndrome. The association of anticonvulsivants, adrenergic alpha-2 agonists, betablockers and antipsychotics with benzodiazepines is recommended for symptom reduction in severe alcohol withdrawal syndrome. Thiamine should be administered to all patients to prevent Wernicke-Korsakoff encephalopathy. If there is any electrolytic imbalance it should be corrected. Maintaining a high level of suspicion for alcohol withdrawal syndrome is important across all clinical settings, and it should be promptly treated.

Phenobarbital for the management of severe acute alcohol withdrawal (the PHENOMANAL trial): a pilot randomized controlled trial

BackgroundBenzodiazepines are considered first-line treatment for patients experiencing severe acute alcohol withdrawal syndrome (sAAWS). Although several medications have been evaluated as potential adjuvant treatments for sAAWS, barbiturates show particular promise.ObjectiveIn the PHENOMANAL trial, we will assess the feasibility of conducting an allocation-concealed, quadruple-blinded, randomized controlled trial (RCT) comparing symptom-triggered benzodiazepine therapy with either a single dose of adjuvant intravenous (IV) phenobarbital (7.5 mg/kg of ideal body weight) or a single dose of matching IV placebo for patients with sAAWS.MethodsWe will recruit adult patients from the Emergency Department, Intensive Care Unit, or hospital wards with a Clinical Institute of Withdrawal – Adult revised (CIWA-Ar) score of 16 or more after receipt of at least 60 mg of diazepam or equivalent within 16 h of diagnosis of sAAWS, and an anticipated need for hospitalization. We will randomize participants (n=39) in a 2:1 manner to treatment and placebo groups, respectively. The primary objective of the PHENOMANAL pilot trial will be to demonstrate our ability to recruit the desired population over the trial period. As secondary objectives, we will evaluate clinician compliance with the treatment protocols, assess crossover rates from the placebo arm to the treatment arm, and obtain preliminary estimates of treatment effect. All trial participants will be followed for 7 days or until hospital discharge.RelevanceThe PHENOMANAL trial is novel in investigating a new treatment for a common and understudied condition, repurposing an existing medication for a novel indication, and addressing an important evidence gap. Through conduct of the multidisciplinary pilot trial, we aim to advance methodology in acute care research through the use of a hybrid consent model and inform the design of a large-scale trial.Trial registrationClinicalTrials.gov Registration NCT03586089; first registered July 13, 2018.

ВЗАИМОСВЯЗЬ БИОХИМИЧЕСКИХ И ГЕНЕТИЧЕСКИХ ПАРАМЕТРОВ, ХАРАКТЕРИЗУЮЩИХ МОЗГОВОЙ НЕЙРОТРОФИЧЕСКИЙ ФАКТОР (BDNF), С ТЯЖЕСТЬЮ АЛКОГОЛЬНОГО АБСТИНЕНТНОГО СИНДРОМА

The purpose of this work is to determine the level of brain neurotrophic factor (BDNF, brain-derived neurotrophic factor) in the blood serum of individuals with alcohol dependence syndrome in the dynamics of alcohol withdrawal syndrome (COA), as well as to compare the results obtained with the clinical picture and the effectiveness of the therapeutic program. Material and methods. The level of BDNF in the blood serum was determined using ELISA. The dynamics of the severity of alcohol withdrawal syndrome (COA), as well as indicators characterizing the psychoemotional status and cognitive abilities of patients, were evaluated using appropriate psychometric scales. The studies were conducted on the 2nd, 8th and 21st days of abstinence. There were examined 70 patients with alcohol dependence syndrome in the dynamics of COA, who met the inclusion criteria and gave informed voluntary consent to participate in the study. Results and discussion. As the symptoms of COA decreased, there was a significant increase in the level of BDNF in the blood serum: on the 21st day of abstinence, the level of BDNF was significantly higher than the values on the 2nd and 8th day of abstinence. On the 8th day of abstinence, BDNF in the blood serum forms a direct correlation with the level of personal anxiety measured using the H scale Ch. Spielberger in the modification of Y.L. Khanin. According to multiple regression analysis on the 21st day of abstinence, BDNF can predict the severity of attraction to alcohol, established using the Pennsylvania scale of attraction to alcohol. Conclusion. Thus, the content of BDNF in the blood serum can act as an independent prognostic marker of the success of care in the treatment of COA.

Research Needs for Inpatient Management of Severe Alcohol Withdrawal Syndrome: An Official American Thoracic Society Research Statement.

Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum.Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T0–T4 continuum to advance the care of hospitalized patients who experience SAWS.Methods: Clinicians and researchers with unique and complementary expertise in basic, clinical, and implementation research related to unhealthy alcohol consumption and alcohol withdrawal were invited to participate in a workshop at the American Thoracic Society 2019 International Conference. The committee was subdivided into four groups on the basis of interest and expertise: T0–T1 (basic science research with translation to humans), T2 (research translating to patients), T3 (research translating to clinical practice), and T4 (research translating to communities). A medical librarian conducted a pragmatic literature search to facilitate this work, and committee members reviewed and supplemented the resulting evidence, identifying key knowledge gaps.Results: The committee identified several investigative opportunities to advance the care of patients with SAWS in each domain of the translational science spectrum. Major themes included 1) the need to investigate non–γ-aminobutyric acid pathways for alcohol withdrawal syndrome treatment; 2) harnessing retrospective and electronic health record data to identify risk factors and create objective severity scoring systems, particularly for acutely ill patients with SAWS; 3) the need for more robust comparative-effectiveness data to identify optimal SAWS treatment strategies; and 4) recommendations to accelerate implementation of effective treatments into practice.Conclusions: The dearth of evidence supporting management decisions for hospitalized patients with SAWS, many of whom require critical care, represents both a call to action and an opportunity for the American Thoracic Society and larger scientific communities to improve care for a vulnerable patient population. This report highlights basic, clinical, and implementation research that diverse experts agree will have the greatest impact on improving care for hospitalized patients with SAWS.

Efficacy and Safety of Anticonvulsants for the Inpatient Treatment of Alcohol Withdrawal Syndrome: A Systematic Review and Meta-analysis.

To examine the efficacy and safety of antiepileptic drugs (AED) for the inpatient treatment of patients with moderate to severe alcohol withdrawal syndrome (AWS). We searched in databases and gray literature to include randomized controlled clinical trials in adults that compare the use of AED versus placebo or any other medication. Studies that did not specify severity or were performed on an outpatient basis were excluded. The outcomes were improvement of symptoms, delirium tremens, seizures and adverse events. Two researchers independently selected the references, extracted the data and assessed the risk of bias. A qualitative synthesis was made and, when the heterogeneity was mild or moderate, a meta-analysis was performed. The quality of the evidence obtained was evaluated with the Grading of Recommendations Assessment, Development and Evaluation tool. In total, 26 studies with 1709 patients were included. No benefit is described in withdrawal syndrome severity measured by scales or in the development of delirium tremens. The only possible meta-analysis showed that there are no differences in the incidence of seizures (risk ratio [RR] = 1.0; confidence interval (CI) 95% 0.76-1.33), even when compared with placebo (RR = 0.95; CI95% 0.57-1.57). There were also no differences in adverse events, although a higher proportion of some mild cases were described with the use of carbamazepine and valproic acid. The routine use of AED is not suggested in the treatment of patients with moderate or severe AWS unless indicated for comorbidity (weak recommendation against using moderate quality of evidence).

Adjunctive Phenobarbital for Alcohol Withdrawal Syndrome: A Focused Literature Review.

To review the literature describing the use of adjunctive phenobarbital in the treatment of severe alcohol withdrawal syndrome (AWS). PubMed and EMBASE were searched using the following terms: phenobarbital, adjunct, refractory or treatment resistant, severe or complicated, and alcohol withdrawal delirium or alcohol withdrawal seizures. The search was limited to randomized controlled trials (RCTs) and cohort studies published in English. Seven studies were identified in the emergency department (ED; RCT, n = 1; cohort, n = 2), general medicine ward (cohort, n = 1), and intensive care unit (ICU; cohort, n = 3) settings. For all studies set in the ED and general medicine ward and for 1 ICU study, phenobarbital plus symptom-guided benzodiazepine therapy was compared to symptom-guided benzodiazepine monotherapy. The other 2 ICU studies examined adjunctive phenobarbital before and after implementation of a protocol, meaning patients in both arms could have received phenobarbital. Overall risk of bias across all studies was low to moderate. The specific role of adjunctive phenobarbital in AWS is not clear because a majority of studies are retrospective cohorts with varying primary outcomes in different patient care settings. In the ED and general medicine ward, phenobarbital demonstrated benzodiazepine-sparing effects. In the ICU, when a protocol guides phenobarbital use, the need for mechanical ventilation may be reduced. Adjunctive phenobarbital was well tolerated. Because of study limitations, it is challenging to provide specific recommendations for adjunctive phenobarbital use in severe AWS.

Patient experiences of alcohol specialist nurse interventions in a general hospital, and onwards care pathways.

To provide insight into patient experiences of a general hospital-based alcohol specialist nurse intervention during alcohol detoxification, experiences of alcohol specialist nurse hospital-based follow-up appointments (Pathway A) as well as the experiences of patients who did not have access to this additional help post detoxification (Pathway B). A longitudinal qualitative study. A thematic analysis of semi-structured interviews (2016-2017) with 24 patient participants (N=12 in each pathway; purposive selection) 1-4weeks post-detoxification and at 3 and 6months, to identify patient experiences of these interventions. Participants gave accounts of how 'empathic' and 'straight talking' interactions with alcohol specialist nurses during detoxification helped them to 'open up' and orient towards change. After detoxification follow-up, outpatient appointments in the hospital setting were seen as supporting change in early recovery and engagement with a wider range of services. Those with no access to nurse follow-up described experiencing a 'void' in available help. Participants in both groups described barriers to engagement with community alcohol services, peer groups and access to help for mild-moderate mental health problems. Patient accounts indicate alcohol specialist nurse interventions during and after unplanned detoxification in a hospital setting can help orient patients towards change and support early recovery. Providing alcohol specialist nurse interventions in general hospitals offers one route to initiating recovery in alcohol-dependent patients. This has potential to improve the lives of those affected and to reduce related demands on hospital services, but further research is needed.