Phenobarbital Group Research Articles

Efficacy of Levetiracetam vs Phenobarbital as First Line Therapy for the Treatment of Neonatal Seizures

OBJECTIVE Seizures are one of the most common neurologic complications seen in a neonate. Historically, phenobarbital has been the agent of choice, but can lead to adverse neurologic outcomes, which has contributed to the use of other agents. Levetiracetam has proven great efficacy with an excellent safety profile in older patients, causing interest of its use in neonates. The objective of this study was to determine if levetiracetam would provide similar neonatal seizure resolution rates as phenobarbital. METHODS The study was a single-center, retrospective, cohort study from August 1, 2020 to August 31, 2022 investigating the efficacy and safety of using levetiracetam compared with phenobarbital as a first line treatment for neonatal seizures. The primary outcome was to assess overall seizure resolution after administration of levetiracetam or phenobarbital, without addition of a second antiseizure medication. RESULTS There were 87 patients included in the study. Fifteen neonates (27.78%) achieved seizure resolution with phenobarbital compared with 9 neonates (27.27%) who received levetiracetam first line (p = 0.959). Neonates who received phenobarbital had higher rates of adverse effects. Neonates who received a benzodiazepine prior to administration of levetiracetam had lower seizure resolution rates (p = 0.021). CONCLUSIONS These findings suggest there is no difference in using phenobarbital over levetiracetam to achieve complete seizure resolution in a neonate. Higher rates of adverse events were seen in the phenobarbital group. The use of a benzodiazepine prior to administration of levetiracetam may reduce the efficacy of levetiracetam.

Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal in the Medical Intensive Care Unit (ICU): A Retrospective Cohort Study.

Background: Phenobarbital (PHB) is a safe and efficacious alternative to benzodiazepines (BZD) for treating severe alcohol withdrawal (AWS). However, the safety of utilizing PHB for patients initially treated with BZD is unknown. Objective: To evaluate the safety and efficacy of PBH compared to BZDs in severe AWS in the medical intensive care unit (ICU). Methods: This was a retrospective cohort study comparing critically ill patients admitted for AWS who received BZDs or PHB. The primary outcome was time to persistent resolution of altered mentation. Secondary outcomes included development and duration of delirium, need for mechanical ventilation, development of withdrawal seizures, and ICU and hospital length of stay. Results: Ninety-five patients were evaluated (53 in PHB group, 42 in BZD group). Before study medication, less BZD patients demonstrated abnormal mentation compared with PHB patients (RASS < -2: 2.39% vsvs. 28.12%, respectively, and RASS > +2: 9.9% vsvs. 48.76%; P <0.001 for both). No difference was seen between groups for the primary outcome (1.8 hours for BZD cohort vsvs. 13.81 hours for PHB cohort; P =0.22). More patients in the BZD cohort developed a seizure after study medication administration (5.67% vs 0%, respectively; P =0.02). No significant difference was seen in other secondary outcomes. Conclusions: This study provides support for use of PHB after BZD if patients remain in uncontrolled withdrawal. Despite significant doses of BZDs before PHB, patients in the PHB cohort demonstrated similar clinical and safety outcomes compared to BZD alone.

Efficacy and safety of rectal chloral hydrate for pediatric procedural sedation: A systematic review and meta-analysis.

To evaluate the efficacy and safety of rectal chloral hydrate (CH) in pediatric procedural sedation. Seven electronic databases and 3 clinical trials registry platforms were searched, and the deadline was August 2022. Randomized controlled trials evaluating the efficacy and safety of rectal CH in pediatric procedural sedation were included by 2 reviewers. The extracted outcomes included the success rate of sedation, sedation latency, sedation duration, and adverse events. The Cochrane risk of bias tool was used to assess the risk of bias. The outcomes were analyzed using Review Manager 5.3 software. Forty-four randomized controlled trials with 8007 children were included in the meta-analysis. The success rate of sedation in the rectal CH group was significantly higher than that in the placebo group (risk ratio [RR], 2.60 [95% confidence interval [CI], 1.74-3.89]; P < .01; RR, 1.24 [95% CI, 1.01-1.54]; P = .04), oral CH group (RR, 1.12 [95% CI, 1.09-1.14]; I2 = 36%; P < .001; number needed to treat [NNT] = 10), diazepam group (RR, 1.21 [95% CI, 1.10-1.33]; I2 = 0%; P < .001; NNT = 6), phenobarbital group (RR, 1.24 [95% CI, 1.13-1.35]; I2 = 12%; P < .001; NNT = 6), and ketamine group (RR, 1.39 [95% CI, 1.20-1.60]; I2 = 20%; P < .001; NNT = 5). There was no significant difference in the success rate of sedation between the rectal CH group and the midazolam group (RR, 0.98 [95% CI, 0.86-1.11]; I2 = 51%; P > .05). The sedation latency was significantly shorter in rectal CH group than that in the oral CH group (mean difference [MD], -6.36 [95% CI, -7.04 to -5.68]; I2 = 49%; P < .001) and the phenobarbital group (MD, -7.64 [95% CI, -9.12 to -6.16]; P < .00001). The sedation duration in the rectal CH group was significantly longer than in the oral CH group (MD, 6.43 [95% CI, 4.39-8.47]; I2 = 0%; P < .001). The overall incidence of adverse events was significantly lower with rectal CH than with oral CH (RR, 0.21 [95% CI, 0.16-0.29]; I2 = 45%; P < .001) and ketamine (RR, 0.26 [95% CI, 0.12-0.60]; I2 = 0%; P = .001). There was no significant difference in the overall incidence of adverse events with rectal CH compared with intramuscular midazolam (RR, 0.55 [95% CI, 0.23-1.28]; P = .17) and intranasal midazolam (RR, 3.00 [95% CI, 0.66-13.69]; P = .16). The available evidence suggests that rectal CH cloud be an effective and safe sedative agent for pediatric procedural sedation.

Safety of Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal in Critically Ill Patients With Primary Neurologic Injuries.

Alcohol withdrawal syndrome (AWS) is a complication of alcohol use disorder that manifests as a range of symptoms. Symptom-triggered benzodiazepines (BZDs) are often used as first-line treatment of AWS. However, recent literature suggests phenobarbital (PHB) may be safer and more efficacious, but studies are limited by exclusion of patients with neurological injuries. We aimed to evaluate the safety of PHB compared to BZDs for the management of AWS among patients with primary neurologic injuries. Retrospective cohort study of patients with primary neurologic injuries admitted to an ICU who received PHB or symptom-triggered BZD for AWS between December 2013 and February 2020. The primary outcome was incidence of oversedation, defined as Richmond Agitation Sedation Scale (RASS) scores from -5 to -3 within 24 hours of initial PHB or BZD dose. Secondary outcomes included largest decrease in RASS, need for mechanical ventilation, and additional sedative use within 24 hours of initial PHB or BZD dose. A multivariable analysis was performed to evaluate the association of PHB administration with the primary outcome. Among 600 patients treated for AWS, 84 patients were included in our analysis (PHB, n = 56; BZD, n = 28). In the unadjusted analysis, there were no differences between the PHB and BZD groups for the primary outcome of oversedation (21.4 vs. 7.1%, P = 0.13), or secondary outcomes of decrease in RASS (P = 0.34), or new ventilator requirement (P = 0.55). Patients who received PHB had higher rates of additional sedative use (P < 0.01). Multivariable regression revealed an increase in oversedation among intubated patients (P = 0.014), while PHB administration was not independently associated with oversedation (P = 0.516). Phenobarbital did not independently increase the risk of oversedation compared to BZD for AWS in patients with primary neurologic injuries. Future studies should determine optimal dosing of PHB in this population.

The Effect of Antiseizure Medications on Thyroid Functions in Children With Epilepsy

In this study, we aimed to investigate the effects of antiseizure medications on serum thyroid-stimulating hormone (TSH), free thyroxin (fT4) levels, and the frequency of subclinical hypothyroidism in children with epilepsy. One hundred and eighty-one pediatric patients receiving valproate, phenobarbital, carbamazepine, and levetiracetam monotherapy were included. The serum TSH levels were significantly higher at 6th, 12th, and 18th months of the treatment compared with the pre-treatment levels in valproate-treated patients. Serum fT4 levels in carbamazepine group were significantly lower than levetiracetam, valproate, and phenobarbital groups at 12th and 18th months of the treatment. Serum fT4 and TSH levels in levetiracetam group showed no significant changes at any time point. The frequency of subclinical hypothyroidism at 18th month was 16% in valproate, 11% in phenobarbital, 7% in carbamazepine, and 0% in levetiracetam groups. Our data suggest that levetiracetam monotherapy does not cause thyroid dysfunction.

Evaluation of the Use of Phenobarbital and Benzodiazepines in the Management of Alcohol Withdrawal Syndrome in Patients Requiring Neurological/Neurosurgical Critical Care: A Propensity-Matched Analysis.

Objective There is growing interest in the use of phenobarbital for alcohol withdrawal syndrome in critically ill patients, though experience in neurologically injured patients is limited. The purpose of this study was to compare the safety and effectiveness of phenobarbital-containing alcohol withdrawal regimens versus benzodiazepine monotherapy in the neurocritical care unit. Methods We conducted a retrospective cohort study of adult patients admitted to the neurocritical care unit from January 2014 through November 2021 who received pharmacologic treatment for alcohol withdrawal. Treatment groups were defined as benzodiazepine monotherapy versus phenobarbital alone or in combination with benzodiazepines. The primary outcome was the percentage of patients requiring intubation after receiving alcohol withdrawal treatment. Secondary outcomes included all-cause, in-hospital mortality, intensive care unit length of stay, discharge disposition, change in Glasgow Coma Scale (GCS) score, and the use of adjunctive agents. Results We analyzed data from 156 patients, with 77 (49%) in the benzodiazepine group and 79 (51%) in the phenobarbital combination group. The groups were well-balanced for baseline characteristics, though more males (67, 85%) were in the phenobarbital group. Only three (1.9%) patients received phenobarbital monotherapy, and the rest (153, 98.1%) received combination therapy. The percentage of patients requiring mechanical ventilation was significantly higher in the phenobarbital combination group compared to benzodiazepine monotherapy (39% (n=31) versus 13% (n=10); OR: 4.33, 95% CI: 1.94-9.66; p<0.001). The use of adjunctive propofol and dexmedetomidine was higher in the phenobarbital group (propofol 35% (n= 28) versus 9% (n=7) and dexmedetomidine 30% (n=24) versus 5% (n=4), respectively). Patients in the phenobarbital group also had lower GCS scores and higher Clinical Institute Withdrawal Assessment of Alcohol (CIWA-Ar) scores during their intensive care unit admission, possibly suggesting more severe alcohol withdrawal. There was no difference in intensive care unit length of stay, all-cause, in-hospital mortality, discharge disposition, or therapeutic adjuncts. Conclusions Combination therapy of phenobarbital plus benzodiazepines was associated with higher odds of requiring mechanical ventilation. Few patients received phenobarbital monotherapy. Additional studies are needed to better compare the effects of phenobarbital monotherapy versus benzodiazepines in neurocritical patients.

Enhancing Sleep Quantity and Quality with a Novel GABAergic Dietary Supplement

Purpose: The primary objective of this investigation was to evaluate the effects of BH_SLP_01 (Bonafide Health Sleep Product) on sleep quality and brain wave patterns using a caffeine-induced insomnia model, and on sleep duration and latency using a pentobarbital-induced sleep model. Methods: Five male BALB/c mice were allocated per treatment arm (age: 8 weeks, body mass: 180 ± 20 g). Treatment arms included control, caffeine or phenobarbital (active) control, and BH_SLP_01. Caffeine treatment model. To induce sleep disturbance, 7.5 mg/kg caffeine was injected intraperitoneally at the 15th minute (min) of recordings, and second injections (saline or combinations) were performed at the 30th minute. Brain electrical activity was monitored and recorded for a total of two hours using electrocorticography (ECoG) recording. Serum melatonin, serotonin, and dopamine were measured by ELISA. Brain levels of MDA were measured by HPLC, and protein concentrations were determined using Western Blot analysis. Phenobarbital treatment model Groups were administered saline or BH_SLP_01, and then, 45 min later, pentobarbital (42 mg/kg) was injected. After injection, sleep latency and duration were measured. Study treatments were compared using an ANOVA and Student's unpaired t-test. Significance levels were set at p&lt;0.05. Results: Analysis of ECoG recording data revealed notable findings. In the caffeine-pretreated group, a significant increase in amplitude was observed during the 30-45 min interval, compared to control. Caffeine administration also significantly increased frequency at 75-90 and 90-105 min compared to control (p&lt;0.05). Conversely, the group treated with BH_SLP_01 displayed no significant changes in amplitude and frequency, except for a significant change in frequency at 90-105 min compared to control (p&lt;0.05). Both sleep duration and sleep latency were significantly improved for BH_SLP_01 compared to control and phenobarbital control (p&lt;0.05). In addition, serotonin, dopamine, melatonin, GABAA R2, GABAB R1, GABAB R2, 5-HT1A, GluA1, GluN1, GluN2A, Bax, Bcl-2, and Caspase-3 levels were significantly improved by BH_SLP_01 compared to control and caffeine control (p&lt;0.05). Conclusion: The results of these studies provide evidence for the effcacy of BH_SLP_01 to improve impaired sleep, leading to notable enhancements in markers of deep sleep. This conclusion is supported by the significant upregulation of GABA, glutamine receptors, and endogenous melatonin, all of which collectively contribute to the augmentation of both sleep quantity and quality. These findings underscore the potential of BH_SLP_01 as a promising therapeutic intervention for optimizing sleep parameters and promoting overall sleep wellness. This research was supported by Bonafide Health, LLC. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Comparative Outcomes of Levetiracetam and Phenobarbital Usage in the Treatment of Neonatal Seizures: A Retrospective Analysis.

The primary aim of this study was to conduct a comparative analysis of the safety and efficacy of levetiracetam (LEV) and phenobarbital (PB) as first-line treatments for neonatal seizure management. This study was designed to measure and compare the incidence of adverse effects and to determine the discharge and mortality rates associated with the use of these antiseizure medications (ASMs). Through this comparison, this research sought to provide insights to optimise care for neonates experiencing seizures. This retrospective cohort study evaluated 104 neonates treated for seizures at Zeynep Kamil Hospital from 2015 to 2020 after excluding those on non-PB/LEV antiseizure medications. Seizures were characterised using electroencephalogram (EEG) and categorised according to aetiology and frequency. Treatment efficacy was gauged by seizure cessation, as confirmed using EEG. Adverse effects and demographic data were recorded. Statistical analyses were conducted using SPSS, employing the Shapiro-Wilk, independent t-test, Mann-Whitney U test, and chi-square test, with a significance threshold of p < 0.05. Overall, 104 neonates treated with first-line ASM were evaluated for efficacy; PB was administered in 68.26% of the cases, while LEV was utilised in 31.74%. The total complete response rate was 40.38%, with no significant difference between the PB and LEV groups (p = 0.309). The incidence rate ratios (IRRs) demonstrated that seizure frequency profoundly influenced treatment effectiveness, with IRRs of 2.09 for rare seizures, 3.25 for frequent seizures, and 4.01 for status epilepticus, indicating a higher treatment response rate with increasing seizure frequency. For second-line treatment, among a subset of 62 patients, PB had a slight, non-significant advantage over LEV, with an odds ratio of 1.09, suggesting a marginally better response to LEV. Adverse events were significantly more frequent in the PB group, affecting 19 of 67 neonates (28.36%), compared to only 2 of 71 neonates (2.82%) in the LEV group (p < 0.001). No significant difference was observed in the discharge rates between the two groups (PB, 67.61%; LEV, 75.76%; p = 0.674). Interestingly, the mortality rate was significantly higher in the LEV group (45.45%) than that in the PB group (22.54%; p = 0.045). This study underscores LEV's superior safety profile over PB in neonatal seizure management, evidenced by a significantly lower rate of adverse events. PB seems to be more effective in the second-line treatment of neonatal seizures. Despite the lack of significant differences in the discharge rates, the higher mortality rate associated with LEV warrants further investigation. These findings advocate the cautious selection of antiepileptic drugs in neonatal care, with a preference for LEV based on its safety profile.

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.

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

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

Phenobarbital ameliorates hyperglycemia-induced angiogenesis in diabetic nephropathy-possible intervention at the HIF-1α/VEGF axis

Hyperglycemia contributes to a cascade of inflammatory responses in kidneys that result in the development of renal hypoxia and angiogenesis with subsequent chronic renal failure. As the hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) axis is a key pathway for neovascularization, the inhibition of this axis is a target for renal angiogenesis therapy. We speculate that Phenobarbital (PB) which has a potential to reduce vascularization in clinical settings might have an influence on the development of angiogenesis in diabetic kidney. The aim of the study was to explore the effects of PB on the HIF-1α and VEGF expression and angiogenesis in renal tissue of rats with hyperglycemia and diabetic nephropathy. Sixty-four male Wistar rats were devided into 4 groups: control group received a single intraperitoneal saline injection; PB group received 0.05% PB orally in drinking water; diabetic group received a single intra-peritoneal STZ (65 mg/kg) injection; PB-STZ group received 0.05% PB orally two weeks before STZ administration. At the end of the experiment period (8 weeks), the kidneys were removed and used for biochemical analyses. Serum glucose, urea and creatinine levels, IL-6 levels in kidney homogenate and changes in HIF-1α and VEGF gene expression were estimated. Hematoxylin-eosin staining was performed for histopathological exa­mination. The results obtained showed that both HIF-1α and VEGF gene expression and IL6 level in diabetic rat group were significantly elevated compared to that in control group, whereas in PB and PB-STZ groups, these indices were significantly down-regulated compared to the diabetic group. Abundant glomerular congestion and mesangial proliferation were detected in diabetic rat renal tissues. However, in PB-treated diabetic group, newly formed vessels were significantly decreased. These findings confirmed that phenobarbital, affecting the HIF-1α/VEGF signaling pathway, ameliorates angiogenesis after hyperglycemic kidney injury. Keywords: angiogenesis, HIF-1α, hyperglycemia, IL6, kidney injury, VEGF

CAR requires Gadd45β to promote phenobarbital-induced mouse liver tumors in early stage.

Phenobarbital (PB) is an archetypal substance used as a mouse hepatocellular carcinoma (HCC) promotor in established experimental protocols. Our previous results showed CAR is the essential factor for PB induced HCC promotion. Subsequent studies suggested Gadd45β, which is induced by PB through CAR activation, is collaborating with CAR to repress TNF-α induced cell death. Here, we used Gadd45β null mice (Gadd45β KO) treated with N-diethylnitrosamine (DEN) at 5 weeks of age and kept the mice with PB supplemented drinking water from 7 to 57 weeks old. Compared with wild type mice, Gadd45β KO mice developed no HCC in the PB treated group. Increases in liver weight were more prominent in wild type mice than KO mice. Microarray analysis of mRNA derived from mouse livers found multiple genes specifically up or down regulated in wild type mice but not null mice in DEN + PB groups. Further qPCR analysis confirmed two genes, Tgfbr2 and irisin/Fndc5, were up-regulated in PB treated wild type mice but no significant increase was observed in Gadd45β KO mice. We focused on these two genes because previous reports showed that hepatic Irisin/Fndc5 expression was significantly higher in HCC patients and that irisin binds to TGF-β receptor complex that includes TGFBR2 subunit. Our results revealed irisin peptide in cell culture media increased the growth rate of mouse hepatocyte-derived AML12 cells. Microarray analysis revealed that irisin-regulated genes in AML12 cells showed a significant association with the genes in the TGF-β pathway. Expression of irisin/Fndc5 and Tgfbr2 induced growth of human HCC cell line HepG2. Thus, Gadd45β plays an indispensable role in mouse HCC development regulating the irisin/Fndc5 and Tgfbr2 genes.

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

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. 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. 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. A PHB-based protocol for the management of AWS is a safe and effective alternative to BZD-based regimens in trauma patients. Therapeutic/Care Management; Level IV.

Long-term follow-up of phenobarbital versus valproate for generalized convulsive status epilepticus in adults: A randomized clinical trial

ObjectiveIntravenous phenobarbital is frequently offered to patients with generalized convulsive status epilepticus (GCSE) in China, but its long-term benefits are unclear. We aimed to evaluate the long-term effects of intravenous phenobarbital on adult patients with GCSE. MethodsThis randomized clinical trial with a 12-month follow-up was performed in Xuanwu Hospital, Capital Medical University (Beijing, China) between February 2011 and December 2021. After the failure of intravenous diazepam treatment, adult patients with GCSE were randomized to receive either intravenous phenobarbital or valproate. Neurological outcome within 12-month was dichotomized as good (modified Rankin scale, mRS 0–2) or poor (mRS 3–6). Cognitive function was measured by mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA). Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) were tested for mood disorders. ResultsWe consecutively recruited 166 patients with GCSE. After excluding individuals with termination after intravenous diazepam (n = 61), and with other exclusion criteria (n = 7), 98 patients were included and 88.0% (66/75) of survivors achieved seizure freedom at 12-month. Forty-five patients (45.92%) had good outcomes at 3-month and 57 patients (58.16%) had good outcomes at 12-month. And 46.67% (35/75) of survivors showed mRS improvement at 12-month (phenobarbital group, n = 17 vs. valproate group, n = 18, P = 0.321). Despite there was no significant difference with respect to good outcomes at 3-month (54.0% vs. 37.5%, P = 0.101), the rate of good outcomes in phenobarbital group was higher than valproate group at 12-month (68.0% vs. 47.92%, P = 0.044). A total of 43 patients successfully participated cognitive and emotional tests. Mild cognitive impairment was found in 7.14% of phenobarbital group and 50.0% in valproate group (P = 0.026). In addition, there were no significant differences with respect to anxiety (36.36% vs. 38.10%) and depression (31.82% vs. 47.62%) between the phenobarbital and valproate groups. ConclusionsCombined with long term conventional therapy, intravenous phenobarbital group had more good outcomes than intravenous valproate group in Chinese adult patients with GCSE up to 12-month follow-up. This finding may prompt the option of intravenous phenobarbital especially in patients with limited access to new antiseizure drugs.

Comparison of caregivers' assessments of clinical outcome in dogs with idiopathic epilepsy administered levetiracetam, zonisamide, or phenobarbital monotherapy.

To investigate caregivers' assessments of outcome in dogs with idiopathic epilepsy (IE) administered levetiracetam (LEV), zonisamide (ZNS), or phenobarbital (PB) monotherapy. 100 dogs with IE administered LEV (n = 34), ZNS (31), or PB (35) monotherapy between January 1, 2003, and February 6, 2019, and survey responses from their caregivers. Information on duration of therapy, adverse effects (AEs), and outcome was obtained from medical record review and caregiver questionnaire. A significant improvement in mean quality of life score was reported during monotherapy (7.7; SD, 2.14) compared to before treatment (6.25; SD, 2.63; P < .0001), with no difference identified between monotherapy groups. Compared to ZNS monotherapy, dogs prescribed PB monotherapy had a significantly younger median age at seizure onset (2.6 vs 4.3 years; P = .024). A significant relationship was identified between the occurrence of reported AEs and monotherapy group, with a higher prevalence in the PB group (77% [27/35]) and a lower prevalence in the ZNS group (39% [12/31]; P = .0066). Treatment failure rates for PB, LEV, and ZNS monotherapy were 51%, 35%, and 45%, respectively, with failure attributed most commonly to inadequate seizure control. No significant difference was identified between groups with respect to rate of or time to failure. Most caregivers reported a favorable outcome with administration of LEV, ZNS, or PB monotherapy to dogs with IE. Phenobarbital is associated with the highest prevalence of AEs but no difference in quality of life score. Prospective controlled studies are needed to further compare the efficacy and safety of these monotherapies in dogs with IE.

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

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. 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. 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. 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. Therapeutic/Care Management; Level III.

1290: PHENOBARBITAL VERSUS BENZODIAZEPINE-BASED REGIMEN FOR ALCOHOL WITHDRAWAL SYNDROME IN TRAUMA PATIENTS

Introduction: Alcohol withdrawal syndrome (AWS) is associated with increased morbidity and mortality in the trauma population. Benzodiazepines (BZD) 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. Safety and efficacy studies of PHB for AWS in trauma patients are lacking. Our aim is to compare a BZD versus PHB regimen 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 a study medication prior to admission, receiving propofol or dexmedetomidine prior to initiation of the study drug, presenting with delirium tremens or seizures, died, or were 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-, ICU-, and ventilator-free days, and length of stay (LOS). Results: 411 patients were identified; 118 received BZD, and 293 received PHB. The odds of developing complicated AWS with PHB versus BZD-based therapy was not statistically significant (OR 0.62; 95% CI, 0.23-1.69); however, patients in the PHB group were less likely to develop uncomplicated AWS (OR 0.09; 95% CI, 0.05-0.17) or require escalation of therapy (OR 0.47; 95% CI, 0.24-0.9). The PHB group had a LOS 3.26 days shorter than the BZD group (p=0.001). There was no difference in ICU-, ventilator-, or delirium-free days. Conclusions: PHB is a safe and effective alternative to BZD-based regimens in the management of AWS in trauma patients.

1105: PHENOBARBITAL VERSUS LORAZEPAM FOR THE MANAGEMENT OF ALCOHOL WITHDRAWAL IN HOSPITALIZED PATIENTS

Introduction: Alcohol withdrawal syndrome (AWS) is a potentially life-threatening medical condition and even though benzodiazepines (BZDs) are the standard of care in the treatment of AWS, therapy-associated complications like respiratory depression requiring ventilatory support and the use of adjunctive pharmacotherapy persist. Studies have shown promising results with phenobarbital (PB), but have been limited to use in the emergency department or as an agent of choice for refractory AWS in the intensive care unit (ICU). Our study aims to compare the ICU admissions rate between lorazepam versus PB in treating AWS in hospitalized patients. Methods: We conducted a retrospective cohort study on patients hospitalized for AWS from 2019 to 2022. Patients were categorized into those who received lorazepam using the revised Clinical Institute Withdrawal Assessment of alcohol scale (CIWA-Ar) and those who received PB based on the Richmond Agitation- Sedation scale (RASS). The primary outcome was the rate of admission to the ICU. Secondary outcomes included total length of hospital and ICU stay, mechanical ventilation rate, use of adjunctive medications and mortality. Results: 300 patients met the inclusion criteria, of whom 148 received lorazepam and 152 received PB. The mean patient age was 56 years and 51 years in the PB and lorazepam groups, respectively (p=0.001). There were significant differences between lorazepam and PB in terms of ICU admission (13.5% vs 5.3%, p=0.014), mechanical ventilation rate (9.5% vs 0.7%, p=0.0004), need for adjunctive dexmedetomidine (9.5% vs 1.3%, p=0.0016) and mean length of hospital days (6.16 vs 4.89 days, p value =0.004), and ICU days (1.07 vs 0.21 days, respectively, p value=0.003). Conclusions: AWS patients treated with PB per protocol were found to have a significantly decreased rate of ICU admission, need for invasive ventilation and adjunctive dexmedetomidine treatment, along with reduced ICU and total length of hospital stay as compared to those treated with lorazepam. We conclude that our results support the growing evidence of efficacy of PB over lorazepam as the primary treatment for AWS patients, due to its mechanism of action that better targets AWS pathophysiology. Prospective, randomized controlled studies that compare PB vs BDZs for AWS are needed.

1146: EARLY VERSUS LATE ADMINISTRATION OF PHENOBARBITAL IN ACUTE ALCOHOL WITHDRAWAL

Introduction: Alcohol withdrawal syndrome (AWS) is the leading cause of mortality in patients with alcohol use disorder due to complications like seizures and delirium tremens. The current standard of care for management is Clinical Institute Withdrawal Assessment (CIWA)-guided benzodiazepine administration. Phenobarbital in addition to a CIWA protocol is shown to be a safe adjuvant in patients with AWS but optimal timing has not been established. The purpose of this study is to evaluate the effects of early vs. late vs. no administration of phenobarbital for the management of AWS. Methods: A retrospective chart review of adult patients in the emergency department (ED) for AWS who received a benzodiazepine or phenobarbital. Exclusion criteria included: pregnancy, study drug use for an indication other than AWS, left against medical advice/discharged within 48 hours, and primary seizure disorder. Study groups were as follows: early (phenobarbital before receiving >30mg of lorazepam equivalents), late (phenobarbital after receiving >30mg of lorazepam equivalents), and none. The primary outcome was cumulative dose of benzodiazepine per day. Secondary outcomes included ICU admissions, reduction of CIWA score from baseline, need for adjuvant agents, and safety outcomes. Results: Seventy-five patients were included in this study (29 early group, 20 late group, 26 none group). Early phenobarbital patients received less benzodiazepines compared to the late and none groups (11.88 mg vs. 36.21 mg vs. 21.29 mg). Average change from baseline CIWA was greater in the early group than in the late and none groups (12.94 vs. 7.89 vs. 5.25). Early phenobarbital compared to late resulted in lower ICU admissions (67.7% vs. 88.0%) and less need for adjuvant therapy (34.3% vs. 64%). More intubations were seen in the early and late groups compared to the no phenobarbital group, but all intubations were due to severe AWS requiring continuous sedation. Conclusions: Phenobarbital led to decreased benzodiazepine requirements, greater change from baseline CIWA score, and less need for adjuvant therapy without an increased risk of adverse effects. Early phenobarbital administration was associated with decreased benzodiazepine requirements, greater change from baseline CIWA score, less ICU admissions, and less need for adjuvant therapy.

323 Phenobarbital Protocol for Alcohol Withdrawal Syndrome Reduces ICU Length of Stay in Trauma and Burn Patients

323 Phenobarbital Protocol for Alcohol Withdrawal Syndrome Reduces ICU Length of Stay in Trauma and Burn Patients