-
Journal of Medical Toxicology :... Jul 2022Phenobarbital is frequently used to manage severe alcohol withdrawal. The purpose of this study was to compare the incidence of mechanical ventilation in patients with...
INTRODUCTION
Phenobarbital is frequently used to manage severe alcohol withdrawal. The purpose of this study was to compare the incidence of mechanical ventilation in patients with benzodiazepine-resistant alcohol withdrawal between front-loaded and low-intermittent phenobarbital dosing strategies.
METHODS
In this retrospective before-after study, we analyzed patients that received phenobarbital for severe alcohol withdrawal syndrome in a tertiary medical ICU. Patients received low-intermittent phenobarbital doses (260 mg intravenous push × 1 followed by 130 mg intravenous push every 15 min as needed) from January 2013 to July 2015, and front-loaded phenobarbital doses (10 mg/kg intravenous infusion over 30 min) from July 2015 to January 2017.
RESULTS
In total, 87 patients met inclusion criteria for this study: 41 received low-intermittent phenobarbital and 46 received front-loaded phenobarbital). The incidence of mechanical ventilation was 13 (28%) in the front-loaded dosing group vs. 26 (63%) in the low-intermittent dosing group (odds ratio 4.4 [95% CI 1.8-10.9]). The cumulative dose of phenobarbital administered and serum phenobarbital levels were similar between both groups, although the front-loaded group had significantly lower benzodiazepine requirements than the low-intermittent group (median 86 mg [IQR 24-197] vs. 228 mg [115-298], P < 0.01) and reduced need for any continuous sedative infusion (OR 7.7 [95% CI 1.6-27], P < 0.01). There was no difference in respiratory failure or hypotension.
CONCLUSIONS
Front-loaded phenobarbital dosing, when compared to low-intermittent phenobarbital dosing, for benzodiazepine-resistant alcohol withdrawal was associated with significantly lower mechanical ventilation incidence and continuous sedative use.
Topics: Alcohol Withdrawal Delirium; Alcoholism; Benzodiazepines; Ethanol; Humans; Hypnotics and Sedatives; Length of Stay; Phenobarbital; Retrospective Studies; Substance Withdrawal Syndrome
PubMed: 35668289
DOI: 10.1007/s13181-022-00900-8 -
Seizure Nov 2022Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available evidence and provide estimates of comparative effectiveness and ranking of treatment effects.
METHODS
All randomized controlled trials studying patients (>1 month of age) with benzodiazepine-resistant SE were included. Outcomes including seizure cessation within 60 min, seizure freedom for 24 h, death, respiratory depression warranting intubation and cardiovascular instability were studied. Conventional and network meta-analyses (NMA) were done.
RESULTS
Seventeen studies were included (16 in NMA). Phenobarbital and high-dose levetiracetam were significantly superior to phenytoin with respect to seizure cessation within 60 min. Network ranking demonstrated that phenobarbital had the highest probability of being the best among the studied interventions followed by high-dose levetiracetam and high-dose valproate. Network meta-analysis was limited by predominant indirect evidence and high heterogeneity.On pairwise comparisons, phenobarbital was found to be associated with a higher risk of need for intubation and cardiovascular instability. Levetiracetam had a better safety profile than fosphenytoin.
CONCLUSIONS
Based on low quality evidence, phenobarbital appears to be the most effective agent for seizure cessation within 60 min of administration in patients with benzodiazepine resistant status epilepticus. High-dose levetiracetam, high-dose valproate and fosphenytoin are probably equally effective. Choice of medication may be guided by effectiveness, safety concerns, availability, cost and systemic co-morbidities.
Topics: Adult; Child; Humans; Anticonvulsants; Benzodiazepines; Levetiracetam; Network Meta-Analysis; Phenobarbital; Phenytoin; Seizures; Status Epilepticus; Valproic Acid; Drug Resistance; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36209676
DOI: 10.1016/j.seizure.2022.09.017 -
Indian Journal of Critical Care... Dec 2019Antiepileptics include various groups of drugs that have different mechanisms of actions and adverse effects. They are often also used to treat other disorders such as...
UNLABELLED
Antiepileptics include various groups of drugs that have different mechanisms of actions and adverse effects. They are often also used to treat other disorders such as psychosis, chronic pain, and migraine. The most common drugs implicated in overdose include phenytoin, sodium valproate, carbamazepine, and phenobarbital. Common signs of toxicity of these drugs are central nervous system manifestations such as altered sensorium, lethargy, ataxia, and nystagmus. Some ingestions can paradoxically precipitate seizures and even status epilepticus. Sodium valproate can cause hyperammonemic encephalopathy and cerebral edema. Carbamazepine is implicated in cardiac arrhythmias and hyponatremia. Phenobarbital causes sedation, respiratory depression, and hypotension. In suspected overdose, apart from the routine laboratory tests, serum levels of the drug should be sent. Serial levels should be measured, as drug toxicity can be prolonged. Treatment of all these overdoses begins with stabilization of airway, breathing, and circulation, and endotracheal intubation being performed to protect the airway in patients with altered mental status. For decontamination, a single dose of activated charcoal should be given. Multidose of activated charcoal may be useful in phenytoin, carbamazepine, and phenobarbital overdose. Naloxone and carnitine are indicated in valproate overdose. Carbamazepine overdose can cause a widened QRS complex and arrhythmias, which can be treated with sodium bicarbonate. Forced alkaline diuresis is no longer advocated for phenobarbital poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup have formulated guidelines for extracorporeal removal of all these drugs. In most cases, hemodialysis is preferred. Other modalities include charcoal hemoperfusion (especially for carbamazepine) or continuous venovenous hemodialysis. Patients who ingest long-acting preparations should be monitored for longer periods.
HOW TO CITE THIS ARTICLE
Murty S. Antiepileptic Overdose. Indian J Crit Care Med 2019;23(Suppl 4):S290-S295.
PubMed: 32021007
DOI: 10.5005/jp-journals-10071-23301 -
Nature Sep 2020Most general anaesthetics and classical benzodiazepine drugs act through positive modulation of γ-aminobutyric acid type A (GABA) receptors to dampen neuronal activity...
Most general anaesthetics and classical benzodiazepine drugs act through positive modulation of γ-aminobutyric acid type A (GABA) receptors to dampen neuronal activity in the brain. However, direct structural information on the mechanisms of general anaesthetics at their physiological receptor sites is lacking. Here we present cryo-electron microscopy structures of GABA receptors bound to intravenous anaesthetics, benzodiazepines and inhibitory modulators. These structures were solved in a lipidic environment and are complemented by electrophysiology and molecular dynamics simulations. Structures of GABA receptors in complex with the anaesthetics phenobarbital, etomidate and propofol reveal both distinct and common transmembrane binding sites, which are shared in part by the benzodiazepine drug diazepam. Structures in which GABA receptors are bound by benzodiazepine-site ligands identify an additional membrane binding site for diazepam and suggest an allosteric mechanism for anaesthetic reversal by flumazenil. This study provides a foundation for understanding how pharmacologically diverse and clinically essential drugs act through overlapping and distinct mechanisms to potentiate inhibitory signalling in the brain.
Topics: Allosteric Regulation; Anesthetics, General; Barbiturates; Benzodiazepines; Bicuculline; Binding Sites; Binding, Competitive; Cryoelectron Microscopy; Diazepam; Electrophysiology; Etomidate; Flumazenil; GABA-A Receptor Antagonists; Humans; Ligands; Models, Molecular; Molecular Conformation; Molecular Dynamics Simulation; Phenobarbital; Picrotoxin; Propofol; Receptors, GABA-A; gamma-Aminobutyric Acid
PubMed: 32879488
DOI: 10.1038/s41586-020-2654-5 -
The Annals of Pharmacotherapy Mar 2021Benzodiazepine is first-line therapy for alcohol withdrawal syndrome (AWS), and phenobarbital is an alternative therapy. However, its use has not been well validated in...
BACKGROUND
Benzodiazepine is first-line therapy for alcohol withdrawal syndrome (AWS), and phenobarbital is an alternative therapy. However, its use has not been well validated in the surgical-trauma patient population.
OBJECTIVE
To describe the use of fixed-dose phenobarbital monotherapy for the management of patients at risk for AWS in the surgical-trauma intensive care unit.
METHODS
Surgical-trauma critically ill patients who received phenobarbital monotherapy, loading dose followed by a taper regimen, for the management of AWS were included in this evaluation. The effectiveness of phenobarbital monotherapy to treat AWS and prevent development of AWS-related complications were evaluated. Safety end points assessed included significant hypotension, bradycardia, respiratory depression, and need for invasive mechanical ventilation.
RESULTS
A total of 31 patients received phenobarbital monotherapy; the majority of patients were at moderate risk for developing AWS (n = 20; 65%) versus high risk (n = 11; 35%). None of the patients developed AWS-related complications; all patients were successfully managed for their AWS. Nine patients (29%) received nonbenzodiazepine adjunct therapy for agitation post-phenobarbital initiation. Three patients (10%) experienced hypotension, and 3 (10%) were intubated. None of the patients had clinically significant bradycardia or respiratory depression.
CONCLUSION AND RELEVANCE
Fixed-dose phenobarbital monotherapy appears to be well tolerated and effective in the management of AWS. Further evaluation is needed to determine the extent of benefit with the use of phenobarbital monotherapy for management of AWS.
Topics: Benzodiazepines; Female; Humans; Hypnotics and Sedatives; Male; Phenobarbital; Retrospective Studies; Substance Withdrawal Syndrome; Wounds and Injuries
PubMed: 32830517
DOI: 10.1177/1060028020949137 -
Clinics in Perinatology Dec 2019The incidence of neonatal abstinence syndrome owing to prenatal opioid exposure has grown rapidly in recent decades and it disproportionately affects rural, non-white,... (Review)
Review
The incidence of neonatal abstinence syndrome owing to prenatal opioid exposure has grown rapidly in recent decades and it disproportionately affects rural, non-white, and public insurance-dependent populations. Treatment consists of pharmacologic and nonpharmacologic interventions with wide variability in approaches across the United States. Standardizing clinical assessment, minimizing unnecessary interruptions, and prioritizing nonpharmacologic and family-centered care seems to improve hospital outcomes. Neonatal abstinence syndrome may have long-term developmental and biological effects, but understanding is limited owing in part confounding biosocial factors. Early intervention and longitudinal support of the infant and family promote better outcomes.
Topics: Analgesics, Opioid; Breast Feeding; Buprenorphine; Female; Humans; Hypnotics and Sedatives; Infant, Newborn; Intensive Care Units, Neonatal; Length of Stay; Methadone; Morphine; Neonatal Abstinence Syndrome; Nurseries, Hospital; Opiate Substitution Treatment; Opioid-Related Disorders; Parents; Phenobarbital; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Rooming-in Care; Severity of Illness Index; Treatment Outcome
PubMed: 31653310
DOI: 10.1016/j.clp.2019.08.012 -
Sleep Medicine Reviews Dec 2021Anti-seizure medications (ASMs) may improve or be detrimental to sleep. A literature review (as an update to the 2014 review by Jain and Glauser... (Review)
Review
Anti-seizure medications (ASMs) may improve or be detrimental to sleep. A literature review (as an update to the 2014 review by Jain and Glauser [https://doi.org/10.1111/epi.12478]) of 25 ASMs of interest (articles from 12 ASMs included) on the effect of ASMs/non-drug treatments on sleep in patients with epilepsy was conducted. The most common objective instrument was polysomnography, and the most common subjective measures were the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index. Eslicarbazepine acetate, lacosamide, and perampanel improved or had no effect on sleep. Perampanel was associated with low incidence of insomnia, and lacosamide with low incidence of daytime sleepiness adverse events. Clonazepam, felbamate, lamotrigine, oxcarbazepine, and phenobarbital worsened or had no effect on sleep. Lamotrigine may be associated with insomnia risk and phenobarbital with daytime sleepiness. Data for valproic acid were mixed. Overall, cannabidiol, carbamazepine, and levetiracetam had no effect on sleep. Epilepsy surgery may benefit sleep in patients with a good surgical outcome. Some ASMs, and, possibly, epilepsy surgery, may have positive effects on sleep, possibly linked to achieving seizure control. Nonetheless, other ASMs may worsen sleep in some settings. Clinicians should consider such observations when making treatment decisions, particularly for patients with comorbid sleep disorders.
Topics: Anticonvulsants; Disorders of Excessive Somnolence; Epilepsy; Humans; Lamotrigine; Sleep
PubMed: 34710770
DOI: 10.1016/j.smrv.2021.101559