First Description of Delirium Tremens was Made by Diego de Torres Villarroel in 1737.

No abstract present.

Successful treatment of severe alcohol withdrawal delirium with very high-dose diazepam (260-480 mg) administration.

INTRODUCTION: Alcohol withdrawal delirium, commonly known as "delirium tremens (DT)", is the most severe clinical condition of alcohol withdrawal syndrome (AWS). Symptoms of DT include changes in consciousness and cognitive and perceptual impairments that fluctuate during the day. Treatment includes general support, such as helping the patient to re-orientate, close monitoring of vital signs and adequate hydration, and symptomatic treatment for agitation, autonomic instability, and hallucinations. In symptomatic treatment of DT, benzodiazepines are most commonly preferred due to their GABA-ergic effects. Diazepam, a benzodiazepine, has a faster onset of action than other benzodiazepines when administered intravenously (iv) and effectively controls symptoms. Although low doses of diazepam usually relieve DT symptoms, very high doses may be required in some patients. This case series discusses patients receiving high doses of diazepam to relieve DT symptoms. CASE REPORT: Four male patients aged from 43 to 57 years who regularly consumed alcohol with a daily average of 20-100 standard drinks and developed DT afterwards and were followed up in the intensive care unit are presented. In these patients, the symptoms of DT were relieved, and somnolence was achieved with the administration of very high-dose IV diazepam (260-480 mg/day), contrary to routine treatment doses. All patients were successfully treated and discharged without any morbidity. CONCLUSION: Severe AWS can potentially result in death otherwise managed quickly and adequately. Diazepam is a suitable agent for severe AWS or DT treatment. Clinicians should keep in mind that high-dose diazepam treatment may be required in the treatment of DT that develops after a long-term and high amount of alcohol consumption. Publications reporting the need for very high doses of diazepam in DT are limited and usually published long ago; in this context, our findings are significant. The evidence is often based on case reports and uncontrolled studies, so controlled trials are needed to determine optimal treatment doses in severe DT.

Characterization of alcohol-related seizures in withdrawal syndrome.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. SIGNIFICANCE: 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. PLAIN LANGUAGE SUMMARY: 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.

Comparison of phenobarbital monotherapy to a benzodiazepine-based regimen for management of alcohol withdrawal syndrome in trauma patients.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is associated with increased morbidity and mortality in the trauma population. Benzodiazepines (BZDs) are standard of care for AWS; however, given the risk of delirium with BZDs and reports of BZD-refractory withdrawal, phenobarbital (PHB) has emerged as an alternative therapy for AWS. Safety and efficacy studies of PHB for AWS in trauma patients are lacking. Our aim was to compare a BZD versus PHB protocol in the management of AWS in trauma patients. METHODS: We performed a retrospective cohort study at a level 1 trauma center of patients at risk for AWS managed with either a BZD or a low-dose oral PHB regimen. Patients were excluded if they were taking BZDs or barbiturates before admission, received propofol or dexmedetomidine before initiation of the study drug, presented with delirium tremens or seizures, or died or discharged within 24 hours of presentation. The primary outcome was complicated AWS (seizures or alcohol withdrawal delirium/delirium tremens). Secondary outcomes included uncomplicated AWS; therapy escalation; oversedation; delirium-, intensive care unit-, and ventilator-free days; and length of stay. RESULTS: A total of 411 patients were identified; 118 received BZD, and 293 received PHB. The odds of developing complicated AWS with PHB versus BZD-based therapy were not statistically significant (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.21-1.39); however, patients receiving PHB were less likely to develop uncomplicated AWS (OR, 0.08; 95% CI, 0.04-0.14) and less likely to require escalation of therapy (OR, 0.45; 95% CI, 0.24-0.84). The PHB group had a length of stay 3.1 days shorter than the BZD group ( p = 0.002). There was no difference in intensive care unit-, ventilator-, or delirium-free days. CONCLUSION: A PHB-based protocol for the management of AWS is a safe and effective alternative to BZD-based regimens in trauma patients. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

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.

Relationship of the 1846G > A Polymorphism of the CYP2D6 Gene to the Equilibrium Concentration Levels of Haloperidol in Patients with Acute Alcoholic Hallucinosis.

Haloperidol is currently used in addictology for the treatment of acute psychotic disorders, including acute alcoholic hallucinosis. The use of haloperidol is often accompanied by the occurrence of adverse drug reactions (ADRs). There is evidence that CYP2D6 isoenzyme is involved in the biotransformation of haloperidol. Aim: The study aimed to evaluate the relationship of 1846G > A polymorphism of the CYP2D6 gene to the equilibrium concentration levels of haloperidol in patients with acute alcoholic hallucinosis. Material and Methods: The study was conducted on 100 male patients with acute alcoholic hallucinosis (mean age 41.4 ± 14.4 years). The efficacy profile was evaluated using the PANSS (Positive and Negative Syndrome Scale) scale. The safety of therapy was assessed using the UKU Side-Effect Rating Scale and the SAS (Simpson-Angus Scale for Extrapyramidal Symptoms) scale. Genotyping was performed using the real-time polymerase chain reaction (Real-time PCR). Equilibrium plasma concentration levels of haloperidol were investigated using the high-performance liquid chromatography with mass spectrometry (HPLC with MS/MS). Results: No statistically significant results were obtained during the therapy efficacy assessment (dynamics of the PANSS score: GG genotype (-13.00 [-16.00; -16.00; -11.00]), GA genotype (-15.00 [-16.75; -13.00], p = 0.728). There was a statistically significant difference in safety assessment scores (dynamics of the UKU score: GG genotype (8.00 [7.00; 10.00]), GA genotype (15.00 [9.25; 18.00], p < 0.001); dynamics of the SAS score: GG genotype (11.00 [9.00; 14.00]), GA genotype (14.50 [12.00; 18.00], p < 0.001). The pharmacokinetic study results showed a statistically significant difference: GG (3.13 [2.32; 3.95]), GA (3.89 [2.92; 5.26], p = 0.010). Thus, a study conducted on a group of 100 patients with acute alcoholic hallucinosis demonstrated an association between the 1846G > A polymorphism of the CYP2D6 gene (rs3892097) and the safety profile of haloperidol therapy. We also revealed the presence of statistically significant difference in the equilibrium concentration levels of haloperidol in patients with the GG and AG genotypes. Conclusion: It can be concluded that patients with the GA genotype have a higher risk of ADRs compared to patients carrying the GG genotype. It is shown that 1846G > A polymorphism of the CYP2D6 gene (rs3892097) has a statistically significant effect on the equilibrium concentration levels of haloperidol.

[Assessment of alcohol withdrawal syndrome: new perspectives]. / Az alkoholmegvonásos szindróma ellátása: új perspektívák.

Alcohol withdrawal syndrome is one of the most important consequences of alcohol use disorder, a complex neuropsychiatric disorder, which is firstly treated in non-specific and secondly in psychiatric/addictive in- or outpatient units. On the other hand, alcohol withdrawal syndrome is one of the most important outcomes of the severity of alcohol use disorder, further, it can lead to the development of alcohol-related seizure and delirium tremens. Hence, early recognition and optimal treatment of alcohol withdrawal syndrome have a critical importance. Therefore, the main goal of the present review was - by systematically summarizing the scientific data published during the past two decades - to form a unique diagnostic and therapeutic algorithm. During the recognition and the course of alcohol withdrawal syndrome, the Clinical Institute Withdrawal Assessment for Alcohol, Revised scale, while in the risk assessment the Prediction of Alcohol Withdrawal Severity Scale are the recommended psychometric tools. Benzodiazepines are the key elements of the pharmacotherapy of alcohol withdrawal syndrome. Many studies have evaluated that diazepam, chlordiazepoxide, lorazepam and oxazepam with distinct indications have sufficient evidence in the treatment of alcohol withdrawal syndrome. However, in the past few years some authors have recommended the importance of non-benzodiazepine medications. The efficacy of propofol, phenobarbital, carbamazepin, oxcarbamazepin and alpha-2 receptor agonists in the treatment of alcohol withdrawal syndrome have been revealed. Furthermore, it has been evaluated that benzodiazepines are recommended in the treatment of alcohol-related seizure and delirium tremens. In the present review, our aim was to construct a unique, up-to-date diagnostic and therapeutic algorithm by summarizing the related papers published during the past two decades. Hence this scheme may be useful in the optimal treatment of patients diagnosed with alcohol use disorder and it could help to conduct further clinical researches. Orv Hetil. 2023; 164(38): 1487-1496.

Assessment of a modified MINDS-based protocol for management of alcohol withdrawal syndrome on an inpatient medical service.

OBJECTIVE: To determine if a novel symptom-based alcohol withdrawal syndrome (AWS) protocol in a US Veterans cohort leads to significant clinical improvements in patient outcomes and safety. BACKGROUND: Prior studies of AWS management, oftentimes using the revised version of the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) index, have demonstrated the effectiveness of symptom-triggered therapy for AWS. The Minnesota Detoxification Scale (MINDS) is an alternative to the CIWA-Ar index but remains unevaluated outside of the intensive care unit (ICU) setting. This study assesses outcomes in AWS management prior to and after the implementation of a novel MINDS-based AWS protocol (SDAWP) utilizing a revised MINDS index (MINDS-rev) in an inpatient medical ward setting. METHODS: Retrospective cohort study including encounters prior to (n = 342) and after (n = 338) the implementation of the protocol. Pre- and post-protocol encounters were selected by combinations of diagnostic codes and charting elements. Outcome measures of AWS management were obtained in both groups. The primary endpoint was median total benzodiazepine exposure. Secondary outcomes included median length of hospitalization, median duration of benzodiazepine administration, and the incidence of complications. RESULTS: The median total benzodiazepine exposure in the post-SDAWP group was significantly lower than the pre-SDAWP group (21.2 vs. 12.0 mg, p < 0.0001) and for a significantly shorter median duration of time (4.0 vs. 3.0 days, p < 0.0001). There was no significant difference in the median length of stay (4.0 vs. 4.0 days, p = 0.50). The incidence of delirium tremens (21 vs. 7, p = 0.01) and need for transfer to a higher level of care (33 vs. 12, p = 0.002) was significantly lower in the post-SDAWP group. CONCLUSION: The SDAWP has provided significant improvements in AWS management in our institution and may potentially serve as a template for wider use in other inpatient settings.

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.

Mortality and alcohol-related morbidity in patients with delirium tremens, alcohol withdrawal state or alcohol dependence in Norway: A register-based prospective cohort study.

BACKGROUND AND AIMS: Little is known about long-term consequences of delirium tremens (DT). This study aimed to compare all-cause and cause-specific mortality and alcohol-related morbidity between patients with: (i) DT, (ii) alcohol withdrawal state (AWS) and (iii) alcohol dependence (AD). DESIGN: A national longitudinal health registry study with linked data from the Norwegian Patient Registry and the Norwegian Cause of Death Registry. SETTING: Norway. PARTICIPANTS: All patients registered in the Norwegian Patient Registry between 2009 and 2015 with a diagnosis of AD (ICD-10 code F10.2), AWS (F10.3) or DT (F10.4) and aged 20-79 years were included (n = 36 287). MEASUREMENTS: Patients were categorized into three mutually exclusive groups; those with DT diagnosis were categorized as DT patients regardless of whether or not they had received another alcohol use disorder diagnosis during the observation period or not. Outcome measures were: annual mortality rate, standardized mortality ratios (SMR) for all-cause and cause-specific mortality and proportion of alcohol-related morbidities which were registered in the period from 2 years before to 1 year after the index diagnosis. FINDINGS: DT patients had higher annual mortality rate (8.0%) than AWS (5.0%) and AD (3.6%) patients, respectively. DT patients had higher mortality [SMR = 9.8, 95% confidence interval (CI) = 8.9-10.7] than AD patients (SMR = 7.0, 95% CI = 6.8-7.2) and AWS patients (SMR = 7.8, 95% CI = 7.2-8.4). SMR was particularly elevated for unnatural causes of death, and more so for DT patients (SMR = 26.9, 95% CI = 21.7-33.4) than for AD patients (SMR = 15.2, 95% CI = 14.2-16.3) or AWS patients (SMR = 20.1, 95% CI = 16.9-23.9). For all comorbidities, we observed a higher proportion among DT patients than among AWS or AD patients (P < 0.001). CONCLUSIONS: People treated for delirium tremens appear to have higher rates of mortality and comorbidity than people with other alcohol use disorders.

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.

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.

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.

Seasonality and Delirium Tremens in Hospitalized Patients with Alcohol Dependence Syndrome.

INTRODUCTION: Due to the high rate of mortality, recognizing the contributing factors of alcohol-related delirium tremens (DT), which is the most severe form of alcohol withdrawal state (AWS) is pivotal in clinical settings. Previous studies suggested relationship between seasonality and other types of delirium; however, to our knowledge, this is the first empirical study which examined the role of seasonality in DT in alcohol dependence syndrome (ADS). METHODS: A retrospective study was undertaken between 2008 and 2015; medical records of 1,591 patients were included, which yielded 2,900 hospital appearances. Three groups were formed based on the ICD-10 diagnoses: ADS, AWS, and DT. The characteristics of the groups were analysed with one-way ANOVA and χ2 tests. Multinomial logistic regression was used to explore the potential predictors of DT, including seasonality. RESULTS: The highest incidence of DT was in spring (36.8%; χ2 (3) = 27.666; p < 0.001), especially in March (13.9%; χ2 (11) = 33.168; p < 0.001). Spring, higher mean age, higher presence of comorbid somatic disorders, and lower occurrence of comorbid psychiatric disorders were significant predictive variables for DT with the control of socio-demographic and clinical variables. CONCLUSIONS: The present study revealed that spring, especially March is a critical period in temperate climate zone regarding DT. This can be interpreted as a late winter effect since the temperature is lower in this month compared to other spring months. Furthermore, higher age and the occurrence of comorbid somatic disorders can be considered as risk factors in case of DT. These results support the need of further clinical studies to better understand the impact of seasonality on DT.

Acute Alcoholic Hallucinosis: A Review.

Acute alcoholic hallucinosis is a psychotic disorder characterized by a predominance of auditory hallucinations with delusions and affective symptoms in the clinical picture. Classically, it develops as part of the alcohol withdrawal syndrome. The prevalence of acute alcoholic hallucinosis ranks second among alcohol-related psychoses after alcohol delirium. The study aimed to systematize the scientific data on the history of alcoholic hallucinosis, its pathogenesis, clinical presentation, and treatment approaches. A literature search was performed in PubMed, Scopus, Google Scholar, and eLibrary. The following words and combinations were used as search strings: (alcoholic hallucinosis OR alcoholic psychosis OR alcohol-related psychosis OR alcohol-induced psychosis OR alcohol-induced psychotic disorder OR complicated alcohol withdrawal syndrome) NOT (animal OR rat OR mouse). The relevant information concerning the history of acute alcoholic hallucinosis, its pathogenesis, clinical picture, and treatment approaches was systematized and summarized. This review presents relevant findings regarding acute alcoholic hallucinosis. Limitations of the review include the use of heterogeneous and mostly descriptive studies and studies on small cohorts of patients.

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.

Neutrophil-lymphocyte ratio as a predictor of delirium tremens in hospitalized patients with alcohol withdrawal.

Delirium tremens (DT) is a severe form of alcohol withdrawal that can be fatal if not recognized early and treated appropriately. In our study, we aimed to determine the role of neutrophil-lymphocyte ratio (NLR), a marker of systemic inflammation, in predicting the development of DT. This retrospective study was conducted in an alcohol and drug treatment center between March 2017 and March 2020. A total of 212 patients with a diagnosis of alcohol use disorder who were admitted to a special care unit after alcohol withdrawal were included. Blood tests were collected within 24 h of the patients' admission. Comparisons were made according to whether the patients developed DT during the hospitalization. DT was diagnosed in 24.1% of the patients. It was determined that higher NLR level (odds ratio [OR]: 4.38, 95% CI: 2.58-7.43) and history of DT (OR: 1.33, 95% CI: 1.23-11.73) are independent risk factors for the development of DT in the logistic regression analysis. The optimal cut-off value of NLR in predicting DT was 2.67 (sensitivity: 82.4%; specificity: 88.8%). The receiver operating characteristic (ROC) curve of NLR showed a larger area under the curve (AUC) than the curves of other systemic inflammation markers. NLR is a simple, practical, and inexpensive marker that can predict the development of DT in patients with alcohol withdrawal syndrome (AWS).

The Use of a Single Dose of Phenobarbital for Inpatient Management of Benzodiazepine Withdrawal: A Case Report.

INTRODUCTION: The current standard of care for physiological dependence to benzodiazepines requires prolonged outpatient tapers, which present challenges for patients and providers. Novel protocols for accelerated benzodiazepine tapers are needed. We describe a case of successful management of benzodiazepine withdrawal in the inpatient setting using a single, loading dose of phenobarbital with adjunctive valproate therapy. CASE REPORT: A 61-year-old woman with benzodiazepine use disorder using 3 to 4 mg of alprazolam daily presented to an inpatient medically supervised withdrawal unit requesting discontinuation of all benzodiazepines and other recreational substances by the time of discharge. Benzodiazepine withdrawal was treated with a single, loading dose of intravenous phenobarbital in line with an approved protocol for the treatment of alcohol withdrawal, as well as adjunctive valproate therapy. The patient experienced resolution of withdrawal symptoms, had no complications, and ongoing abstinence at 60 days of follow-up. DISCUSSION: A single loading dose of phenobarbital in the inpatient setting is a viable alternative to prolonged outpatient tapers for the management of benzodiazepine withdrawal. Although this strategy requires further optimization, the prospect of a single-dose treatment for benzodiazepine withdrawal creates exciting opportunities for alternative management options and settings. CONCLUSIONS: This case describes the successful management of benzodiazepine withdrawal syndrome using a single loading dose of intravenous phenobarbital derived from an approved protocol for alcohol withdrawal syndrome.