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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Phenobarbital is as safe and effective as benzodiazepine-based protocols for the treatment of high-risk alcohol withdrawal, with lower rates of delirium.

Use of Gabapentin for Alcohol Withdrawal Syndrome in the Hospital Setting: A Randomized Open-Label Controlled Trial.

Background/objectives: Patients hospitalized with alcohol withdrawal syndrome (AWS) are typically treated with CIWA-directed benzodiazepines to prevent complications, such as seizures and delirium tremens. Gabapentin is an evidence-based alternative to benzodiazepines in the outpatient setting, but there is limited data for hospitalized patients with AWS. This study compared fixed-dose gabapentin to CIWA-directed benzodiazepines for AWS in the hospital setting. Methods: This open-label, randomized controlled trial enrolled 88 adults from February 1, 2017 to August 16, 2020 with a risk of complicated alcohol withdrawal as defined by the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) ≥4. Patients were randomized within 16 h of admission to either fixed-dose gabapentin taper or continued CIWA-directed benzodiazepine administration. The primary outcome was the length of stay (LOS). Secondary outcomes included seizure, delirium tremens, ICU transfer, and patient-reported symptoms (alcohol cravings, anxiety, sleepiness). Results: LOS was shorter, but not statistically different in the gabapentin group compared to the benzodiazepine group. Because benzodiazepines were received in both gabapentin and benzodiazepine groups before randomization, the mean amount of benzodiazepines received in each group was also not statistically different, although the amount received by the gabapentin group was less than half of that received by the benzodiazepine group (4.3 vs. 10.6 mg, p = 0.146 by per protocol analysis). There were no statistical differences in secondary measures. Conclusions: Fixed-dose gabapentin taper showed similar outcomes compared to CIWA-directed benzodiazepines for the treatment of hospitalized patients with mild/moderate AWS, but the interpretation of the results is limited due to under-enrollment and the use of benzodiazepines in both groups pre-enrollment.Clinical trial registration: NCT03012815.

Delirium Tremens and Central Pontine Myelinolysis in a Patient with Alcohol Use Disorder and Pneumonia: a Case Report and a Narrative Review.

INTRODUCTION: Delirium tremens (DT) is a serious condition occurring in alcohol withdrawal syndrome. Alcohol consumption may also cause additional health problems, such as respiratory infections or neuropsychiatric conditions such as central pontine myelinolysis. In this clinical scenario, managing DT can be expected to be more compelling and complex. Alcohol decreases coughing and mucociliary clearance and disrupts the immunity of the respiratory system. CASE: Here we report on a middle-aged man with alcohol use disorder who had developed DT due to alcohol withdrawal and comorbid pneumonia. DISCUSSION AND CONCLUSION: In this paper, DT, the relation between respiratory infections and alcohol intake, and the correlation of alcohol consumption and central pontine myelinolysis (CPM) are discussed. Also, the literature on alcohol consumption and the additional respiratory and neurologic problems resulting from it are presented.

The Devil Is in the Details: Neurological Diseases Presenting as Religious Hallucinations in Two Literary Works.

Few authors in the Western literature have acquired such a monumental reputation as Thomas Mann and Fyodor Dostoyevsky; although with different backgrounds and aesthetic peculiarities, their writings converge thematically in their frequent relationship with disease. From Dostoyevsky's struggle with epilepsy to Mann's descriptions of tuberculosis and cholera, many are the examples found in their body of work describing medical afflictions. One noteworthy similarity in their works is the presence of hallucinations with Mephistopheles-like devilish entities, possibly caused by neurological diseases: in Mann's case, concerning the main character of Doctor Faustus, caused by neurosyphilis, while for Dostoyevsky, concerning one of the titular Brothers Karamazov, by delirium tremens. In both cases, the authors leave room for ambiguity, with the characters themselves casting doubts on whether their experiences were indeed caused by their disease or by an actual supernatural being. In this, we may find an interesting intersection between neurology and the literature.

[Alcohol withdrawal and its major complications]. / Der komplizierte Alkoholentzug: Grand-Mal-Anfälle, Delir und Wernicke-Enzephalopathie.

Delirium tremens is one of the most common complications of alcohol withdrawal. It is potentially lethal and therefore should be detected as early as possible and be monitored and treated intensively. The assessment of risk factors with the Luebeck Alcohol-Withdrawal Risk Scale short form (LARS-11) can help to predict the risk of severe withdrawal adequately. As delirium cannot be differentiated from Wernicke-Encephalopathy with sufficient certainty high parenteral doses of Vitamin B1 and Magnesium orally should be given in case of any severe withdrawal symptoms. According to guidelines delirium tremens should be treated with benzodiazepines besides adequate electrolyte and fluid substitution. Haloperidol is often additionally given to better control hallucinations. Delirium tremens usually subsides within 10 days of treatment.The article gives an overview of alcohol withdrawal with its different facets, its differential diagnoses, and the treatment options.

Delirium Tremens Leads to Poor Outcomes for Acute Coronary Syndrome.

OBJECTIVES: The mortality rate for patients with delirium tremens (DT) is 5%. As these patients present with elevated cardiac indices, coexisting DT in acute coronary syndrome (ACS) likely worsens outcomes. Our aim was to examine the outcomes of alcohol withdrawal syndrome (AWS) and DT in patients with ACS. METHODS: We used the Nationwide Inpatient Sample (2000-2009) for our study. A multivariable logistic regression model was used to examine the independent association of AWS on inhospital mortality and a multivariable linear regression was used to examine the effect of AWS on inpatient length of stay (LOS). RESULTS: An estimated 2,465,852 admissions with a primary diagnosis of ACS were analyzed. Of these, 4,499 patients had AWS and 3,460 patients had DT. Adjusting for age, gender, race, insurance, hospital characteristics, Charlson's comorbidity index, stent placement and year, the inhospital mortality was significant only for DT (OR 1.56; 95% CI 1.21-2.04). Inpatient LOS was 1.64 (95% CI 1.58-1.73) times higher in those with AWS and 2.33 (95% CI 2.22-2.43) times higher in DT when compared to nonalcoholics. Total hospital charges were higher for patients with AWS and DT when compared to nonalcoholics. CONCLUSIONS: Coexisting DT in ACS admissions is associated with increased mortality along with longer inpatient LOS and higher hospital costs.

Influence of microelement concentration on the intensity of alcohol withdrawal syndrome.

AIMS: To establish a nutritional and constitutional profile concerning the micronutrient plasma concentration of patients who suffer from AWS. METHOD: Observational case control study to determine whether patients who exhibited symptoms of AWS (N = 60) had micronutrient plasmatic concentration deficiencies when compared with healthy controls (N = 34). RESULTS: There were statistically significant differences between the concentrations of nutrients that are correlated with glutamate hyperactivity (zinc, magnesium and folate/vitamin B12/homocysteine). CONCLUSION: Evidence from literature and our experiment suggests that brain activity, especially the glutamatergic system, might be directly involved in micronutrient concentrations. Therefore, their supplementation to the AWS patient might improve symptom evolution.

Resection of the innominate artery to prevent an impending tracheoinnominate fistula and to permit tracheotomy in a patient with subglottic stenosis and high-riding innominate.

OBJECTIVE: This study aimed to determine the long-term viability of innominate artery resection and tracheotomy for a patient at high risk of developing a tracheoinnominate fistula (TIF) in the setting of subglottic stenosis and a high-riding innominate artery. METHODS: Chart review with 2-year follow-up. RESULTS: A 45-year-old diabetic man with obstructive sleep apnea and multiple admissions for coma and delirium tremens associated with alcohol abuse developed subglottic stenosis. He was found to have a palpable supraclavicular pulse during preoperative examination for a tracheotomy. Computed tomography examination revealed a high-riding innominate artery at the level of stenosis along with granulation tissue and disruption of the cartilaginous trachea, suggesting a high risk of impending TIF. The patient underwent a sternotomy-approach resection of the innominate artery with closure of the distal stump with a sternohyoid muscle flap. Intraoperatively, a plane of adhesions between the posterior innominate artery and trachea was dissected. The anterior tracheal wall appeared calcified but without evidence of erosion of either the trachea or the artery. Six weeks later, a tracheotomy was performed. Follow-up at 27 months did not identify complications from the innominate artery resection. CONCLUSION: Resection of the innominate artery is an option for some patients either to address the warning signs of TIF or to permit a tracheotomy to be performed in the presence of a high innominate artery.

Alcohol dependence in the Naval Service.

Alcohol misuse is a significant occupational health issue in the United Kingdom Armed Forces. Dependence associated with alcohol misuse represents the severe end of the clinical and occupational consequences of sustained alcohol misuse. This article aims to explore the diagnosis, management and occupational considerations of alcohol dependence in the Naval Service environment.

Agrypnia excitata.

Agrypnia (from the Greek: to chase sleep) excitata (AE) is a syndrome characterized by loss of sleep and permanent motor and autonomic hyperactivation (excitata). Disruption of the sleep-wake rhythm consists in the disappearance of spindle-delta activities, and the persistence of stage 1 non-rapid eye movement (NREM) sleep. Rapid eye movement (REM) sleep persists but fails to stabilize, appearing in short recurrent episodes, isolated, or mixed with stage 1 NREM sleep. Diurnal and nocturnal motor, autonomic and hormonal overactivity is the second hallmark of AE. Of particular interest is the finding that norepinephrine secretion is extremely elevated at all hours of the day and night whereas the nocturnal melatonin peak is lacking. Oneiric stupor is probably an exclusive sign of AE and consists in the recurrence of stereotyped gestures mimicking simple daily life activities. Agrypnia excitata aptly defines 3 different clinical conditions, fatal familial insomnia (FFI), an autosomal dominant prion disease, Morvan syndrome (MS), an autoimmune encephalitis, and delirium tremens (DT), the alcohol withdrawal syndrome. Agrypnia excitata is due to an intralimbic disconnection releasing the hypothalamus and brainstem reticular formation from cortico-limbic inhibitory control. This pathogenetic mechanism is visceral thalamus degeneration in FI, whereas it may depend on autoantibodies blocking voltage-gated potassium (VGK) channels within the limbic system in MS, and in the sudden changes in gabaergic synapses down-regulated by chronic alcohol abuse within the limbic system in DT.

Symptom profile and outcome of delirium associated with alcohol withdrawal syndrome: a study from India.

AIM: To study the profile of delirium associated with alcohol withdrawal syndrome (AWS) in a developing country in terms of symptomatology, associated risk factors/physical complications, and outcome. METHODOLOGY: Using a prospective design, 112 patients in whom delirium could be attributed to AWS as either the sole or a contributory cause were assessed by Delirium Rating Scale-Revised-98 and the associated etiological factors were assessed by using delirium etiology checklist. FINDINGS: In all patients, delirium was acute in onset and all patients had disturbance of sleep-wake cycle and inattention. Other common symptoms were: disorientation (99.1%), fluctuation in symptoms (97.3%), motor agitation (94.6%), and short-term memory disturbance (92.9%). In terms of delirium etiology checklist etiological categories, besides alcohol withdrawal, the most common factors were metabolic/endocrine abnormalities (76%), followed by organ insufficiency and infection (37% and 35%, respectively). Most patients (67%) improved or recovered completely from delirium during the short stay of 4 days. During the short stay of mean duration of 4 days 13.4% of the patients died during the hospital stay. CONCLUSION: Delirium associated with alcohol withdrawal is characterized by an acute onset of symptoms with high prevalence of disturbance of sleep-wake cycle, inattention, disorientation, fluctuation in symptoms, motor agitation, and disturbance in short-term memory. There are certain differences in the symptom profile of delirium associated with alcohol withdrawal and that associated with medical-surgical causes. About one-sixth of the patients developing delirium due to alcohol withdrawal die during the short hospital stay of 4 days.

A challenging case of lumbar vertebral burst fracture with alcohol withdrawal delirium: A case report.

BACKGROUND: Delirium tremens is a symptom of alcohol withdrawal syndrome that occurs 48 to 96 hours after the last drink in 5% of withdrawing patients. METHODS: This report describes the clinical progression of a case of lumbar vertebral burst fracture with alcohol withdrawal delirium that was difficult to manage. RESULTS: A 47-year-old man was rushed to our hospital complaining of lumbar back pain and numbness in both lower extremities resulting from a 6-m fall during civil engineering work. Computed tomography (CT) revealed a L1 burst fracture with a highly protruding bone fragment in the spinal canal. Magnetic resonance imaging disclosed significant compression of the conus and intramedullary signal changes. We immediately performed posterior spinal fusion and vertebroplasty using instrumentation. On the 4th postoperative day, he became severely agitated, as diagnosed as having delirium tremens related to alcohol withdrawal syndrome, and soon began appropriate medication with diazepam. Although his symptoms persisted until 6 days postoperatively, follow-up CT detected no evidence of screw loosening or breakage. CONCLUSION: We encountered a patient with severe delirium tremens developing several days after thoraco-lumbar fusion surgery. Prompt internal fixation successfully treated the spinal injury and prevented neurological damage. It may also be necessary to consider treatment strategies for patients with a background of heavy alcohol consumption in consideration of delirium tremens and other symptoms of alcohol withdrawal.

Current evidence and clinical utility of phenobarbital for alcohol withdrawal syndrome.

BACKGROUND: Phenobarbital (PB) has been acknowledged among clinicians as a potential alternative to benzodiazepines (BZD) to decrease the need for hospital length of stay and complications associated with alcohol withdrawal syndrome (AWS). However, the level of evidence, including appropriate dosing, is unclear. We aim to summarize the evidence regarding PB used in AWS and provide future agendas for research. METHODS: Following the PRISMA guidelines, we searched MEDLINE, EMBASE, ClinicalTrials.gov, and WHO ICTRP for all peer-reviewed articles and clinical trials using keywords including"alcohol withdrawal", "delirium tremens", "phenobarbital," and "barbiturate" from their inception to September 18, 2022. RESULTS: We included 20 articles, nine in the emergency department (ED) and 11 in the general floors or intensive care units (ICUs). Studies performed in the ED included two RCTs, although both suffered from a considerably small sample size. Six studies done in the general floors or ICUs compared PB and BZD monotherapy, while four compared the utility of adjunct PB in addition to BZD compared with BZD monotherapy and one was a database study without specific dosing information. Overall, there was considerable heterogeneity in PB dosing, measured outcomes, and AWS severity measurement scales. CONCLUSION: This systematic review summarizes the current evidence related to PB use in AWS. While considerable heterogeneity exists among studies available, PB as monotherapy without BZD may be a safe and effective alternative in AWS treatment. Future prospective studies or trials should focus on the standardization of PB dosing and outcomes.

An innovative inpatient protocol for alcohol withdrawal prevention in a 16-year-old adolescent: a case report.

BACKGROUND: Alcohol cessation in youth with daily drinking poses a risk of severe and life-threatening alcohol withdrawal. If unsupervised, alcohol withdrawal in heavy users can cause severe complications, such as seizures, delirium tremens, and death. We present the case of a teenager admitted at our pediatric center for the prevention of alcohol withdrawal using an innovative protocol, including a fixed-dosage benzodiazepine regimen. CASE DESCRIPTION: A 16-year-old Caucasian male, known to have anxiety and an attention deficit disorder, was electively admitted for medical stabilization and surveillance of alcohol withdrawal. He had been previously diagnosed with alcohol use disorder and had a past history of withdrawal symptoms. He was prescribed a course of thiamine, folic acid, as well as a fixed-dosage benzodiazepine taper over 5 days. His withdrawal symptoms were evaluated using a standardized Clinical Institute Withdrawal Assessment for Alcohol scale. During his stay, he reported minimal symptoms, as well as a score on the Clinical Institute Withdrawal Assessment for Alcohol scale consistently lower than 5. His mood, motivation, eating habits and sleeping patterns significantly improved during his stay. He developed no medical complications and demonstrated pride in his successes. He was successfully transferred to a long-term rehabilitation center. CONCLUSIONS: A withdrawal prevention protocol was developed on the basis of existing literature. It included a soothing environment, basic laboratory work evaluating the medical complications of alcohol use, as well as medication aiming to prevent and reduce potential withdrawal symptoms. The patient responded well to the fixed-dosage taper with minimal symptoms and discomfort. Although alcohol use in adolescents is frequent, alcohol withdrawal in this population is rarely seen in a pediatric hospital setting. Nonetheless, given the lack of existing guidelines regarding alcohol withdrawal in adolescents, standardized protocols could be greatly beneficial for the prevention of this condition in this population.

Evaluation of phenobarbital for prevention of alcohol withdrawal in trauma patients.

BACKGROUND: Up to 30% of trauma patients experience alcohol withdrawal syndrome (AWS) during their hospital admission, which is associated with worse outcomes. While benzodiazepines and phenobarbital are the mainstay of AWS management, there are limited data on the prevention of AWS. The objective was to evaluate the safety and efficacy of phenobarbital for the prevention of AWS. METHODS: Adult patients admitted to a level 1 trauma center who received at least one dose of phenobarbital for the prevention of AWS between January 2019 and August 2021 were included. Patients were case matched to a control group managed with symptom-triggered therapy based on risk of AWS. Risk factors included sex, age, history of AWS/delirium tremens or withdrawal seizures, selected laboratory values, and screening questionnaires. The primary endpoint was the need for rescue therapy. Secondary endpoints included the time to rescue therapy, intensive care unit (ICU) length of stay (LOS), and hospital LOS. RESULTS: Overall, 110 patients were included with 55 patients in each group. The phenobarbital group had higher baseline Injury Severity Scores ( p = 0.03) and were more likely to be admitted to the ICU (44% vs. 24%; p = 0.03). The phenobarbital group required less rescue therapy (16% vs. 62%; p < 0.001) with a longer time to rescue therapy administration (26 vs. 11 hours; p = 0.01). The phenobarbital group had a longer hospital LOS (216 vs. 87 hours; p = 0.0001) but no difference in ICU LOS ( p = 0.36). There was no incidence of delirium tremens or seizures and no difference in intubation rates ( p = 0.68). There was no incidence of hypotension associated with phenobarbital. CONCLUSION: Patients managed with phenobarbital had a lower need for rescue therapy for AWS with no increased adverse effects. Further studies should evaluate a protocol to prevent alcohol withdrawal in the trauma population. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Clinical management of the alcohol withdrawal syndrome.

Up to half of individuals with a history of long-term, heavy alcohol consumption will experience the alcohol withdrawal syndrome (AWS) when consumption is significantly decreased or stopped. In its most severe form, AWS can be life-threatening. Medically assisted withdrawal (MAW) often forms the first part of a treatment pathway. This clinical review discusses key elements of the clinical management of MAW, necessary adjustments for pregnancy and older adults, likely outcome of an episode of MAW, factors that might prevent completion of the MAW process and ways of overcoming barriers to ongoing treatment of alcohol use disorder. The review also discusses the use of benzodiazepines in MAW. Although there is clear evidence for their use, benzodiazepines have been associated with abuse liability, blunting of cognition, interactions with depressant drugs, craving, delirium, dementia and disrupted sleep patterns. Because glutamatergic activation and glutamate receptor upregulation contribute to alcohol withdrawal, anti-glutamatergic strategies for MAW and other potential treatment innovations are also considered.

Quantitative electroencephalographic analysis of delirium tremens development following alcohol-withdrawal seizure based on a small number of male cases.

INTRODUCTION: Seizures and delirium tremens (DTs) are recognized as severe alcohol-withdrawal symptoms. Prolonged admission and serious complications associated with alcohol withdrawal are responsible for increased costs and use of medical and social resources. This study investigated the predictive value of quantitative electroencephalography (QEEG) for developing alcohol-related DTs after alcohol-withdrawal seizure (AWS). METHODS: We compared differences in QEEG in patients after AWS (n = 13). QEEG was performed in the intensive care unit within 48 h of admission, including in age- and sex-matched healthy controls. We also investigated the prognostic value of QEEG for the development of alcohol DTs after AWS in a retrospective, case-control study. The spectral power of each band frequency and the ratio of the theta to alpha band (TAR) in the electroencephalogram were analyzed using iSyncBrain® (iMediSync, Inc., Korea). RESULTS: The beta frequency and the alpha frequency band power were significantly higher and lower, respectively, in patients than in age- and sex-matched healthy controls. In AWS patients with DTs, the relative beta-3 power was lower, particularly in the left frontal area, and the TAR was significantly higher in the central channel than in those without DTs. CONCLUSION: Quantitative EEG showed neuronal excitability and decreased cognitive activities characteristic of AWS associated with alcohol-withdrawal state, and we demonstrated that quantitative EEG might be a helpful tool for detecting patients at a high risk of developing DTs during an alcohol-dependence period.

A multifaceted quality improvement intervention to improve management of alcohol withdrawal on a general medicine ward: impact on benzodiazepine use.

OBJECTIVE: To measure the effects of a quality improvement intervention on length of stay and benzodiazepine use among patients admitted for alcohol use disorder. METHODS: This retrospective cohort study was performed at the Salt Lake City Veterans Affairs Medical Center. Patients 18 years and older admitted to a general medical ward with a diagnosis of alcohol related disorders who were treated for alcohol withdrawal were included. The baseline cohort included patients admitted over 12 months. The post-intervention cohort included patients admitted over 12 months. Primary outcomes were total benzodiazepine dose and length of stay. Secondary outcomes included episodes of delirium tremens and seizures. RESULTS: Total benzodiazepine dose decreased significantly over the intervention period. Length of stay also decreased. No episodes of delirium tremens or seizures were observed. CONCLUSIONS: A quality improvement intervention directed at general medicine inpatients admitted for alcohol withdrawal was associated with reductions in total benzodiazepine administration and length of stay.