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Topics in Companion Animal Medicine Dec 2014Phenobarbital-responsive sialadenosis (PRS) is a rare idiopathic disease in dogs. Vomiting, retching, and gulping with bilateral enlargement of the submandibular...
Phenobarbital-responsive sialadenosis (PRS) is a rare idiopathic disease in dogs. Vomiting, retching, and gulping with bilateral enlargement of the submandibular salivary glands are the more frequent clinical signs. A thorough diagnostic examination must be performed to rule out the most important systemic etiologies involved with chronic vomiting, as there is no specific test to diagnose PRS. Diagnosis is confirmed clinically by a rapid and dramatic improvement of clinical signs after instauration of phenobarbital treatment. The aim of this article is to describe the clinical presentation, diagnostic findings, and outcome of a case series of 4 dogs with presumptive PRS.
Topics: Animals; Diagnosis, Differential; Dog Diseases; Dogs; Female; GABA Modulators; Male; Phenobarbital; Sialadenitis
PubMed: 25813851
DOI: 10.1053/j.tcam.2015.01.003 -
Epilepsia Sep 2023The Salzburg criteria for nonconvulsive status epilepticus (NCSE) and the American Clinical Neurophysiology Society (ACNS) Standardized Critical Care EEG Terminology...
OBJECTIVE
The Salzburg criteria for nonconvulsive status epilepticus (NCSE) and the American Clinical Neurophysiology Society (ACNS) Standardized Critical Care EEG Terminology 2021 include a diagnostic trial with intravenous (IV) antiseizure medications (ASMs) to assess electroencephalographic (EEG) and clinical response as a diagnostic criterion for definite NCSE and possible NCSE. However, how to perform this diagnostic test and assessing the EEG and clinical responses have not been operationally defined.
METHODS
We performed a Delphi process involving six experts to standardize the diagnostic administration of IV ASM and propose operational criteria for EEG and clinical response.
RESULTS
Either benzodiazepines (BZDs) or non-BZD ASMs can be used as first choice for a diagnostic IV ASM trial. However, non-BZDs should be considered in patients who already have impaired alertness or are at risk of respiratory depression. Levetiracetam, valproate, lacosamide, brivaracetam, or (if the only feasible drug) fosphenytoin or phenobarbital were deemed appropriate for a diagnostic IV trial. The starting dose should be approximately two thirds to three quarters of the full loading dose recommended for treatment of status epilepticus, with an additional smaller dose if needed. ASMs should be administered during EEG recording under supervision. A monitoring time of at least 15 min is recommended. If there is no response, a second trial with another non-BDZ or BDZs may be considered. A positive EEG response is defined as the resolution of the ictal-interictal continuum pattern for at least three times the longest previously observed spontaneous interval of resolution (if any), but minimum of one continuous minute. For a clinical response, physicians should use a standardized examination before and after IV ASM administration. We suggest a definite time-locked improvement in a focal deficit or at least one-step improvement on a new dedicated one-domain 10-level NCSE response scale.
SIGNIFICANCE
The proposed standardized approach of a diagnostic IV ASM trial further refines the ACNS and Salzburg diagnostic criteria for NCSE.
Topics: Humans; Administration, Intravenous; Benzodiazepines; Electroencephalography; Phenobarbital; Status Epilepticus; Clinical Trials as Topic
PubMed: 37350392
DOI: 10.1111/epi.17694 -
Alcohol (Fayetteville, N.Y.) Feb 2020A symptom-triggered lorazepam regimen is the standard for treating alcohol withdrawal syndrome (AWS) in an inpatient setting. However, in severe AWS, lorazepam... (Comparative Study)
Comparative Study
A symptom-triggered lorazepam regimen is the standard for treating alcohol withdrawal syndrome (AWS) in an inpatient setting. However, in severe AWS, lorazepam requirements can reach significant amounts and lead to risk of delirium and propylene glycol toxicity. Phenobarbital has been shown to be an effective adjunctive therapy for AWS, reducing benzodiazepine use, in the emergency department. The purpose of this study is to determine the efficacy and safety of phenobarbital in adjunct to symptom-triggered lorazepam for severe AWS vs. lorazepam alone in the intensive care unit (ICU). A retrospective cohort was conducted at Cleveland Clinic hospitals from 2013 to 2018 of ICU patients with AWS receiving either phenobarbital adjunct to symptom-triggered lorazepam or lorazepam alone. The primary outcome was the total duration of treatment. Secondary outcomes include ICU length of stay, change in CIWA-Ar score at 24 h, incidence of hypotension, mechanical ventilation, and serum osmolar gap. A total of 72 ICU patients were included with 36 patients in each arm. The median duration of treatment in the phenobarbital adjunct arm was 2.7 days (IQR = 1.7-6.4), compared to 3.1 days (IQR = 1.6-4.8) in the lorazepam arm (p = 0.578). The median ICU length of stay was similar between both arms [4.1 days (IQR = 2.4-8.4) vs. 4.5 days (IQR = 2.8-6.1), p = 0.727]. The average change in CIWA-Ar from baseline at 24 h was significantly lower for those who received phenobarbital (1.8 ± 9.0 vs. 6.5 ± 8.5, p = 0.028). Three patients in the phenobarbital-adjunct group received mechanical ventilation after starting phenobarbital treatment. There were no new incidences of hypotension or increased osmol gap >10 mmol/L after starting treatment in both groups. In conclusion, phenobarbital is an effective adjunct to symptom-triggered lorazepam in severe alcohol withdrawal in the ICU with no significant difference in adverse events.
Topics: Adult; Aged; Alcoholism; Central Nervous System Agents; Drug Therapy, Combination; Ethanol; Female; Humans; Hypotension; Intensive Care Units; Length of Stay; Lorazepam; Male; Middle Aged; Phenobarbital; Respiration, Artificial; Retrospective Studies; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome
PubMed: 31326601
DOI: 10.1016/j.alcohol.2019.07.004 -
Journal of Intensive Care Medicine Sep 2020Alcohol withdrawal syndrome (AWS) is a common reason for admission to a medical intensive care unit (MICU) and requires significant hospital resource utilization.... (Observational Study)
Observational Study
BACKGROUND
Alcohol withdrawal syndrome (AWS) is a common reason for admission to a medical intensive care unit (MICU) and requires significant hospital resource utilization. Benzodiazepines are first-line therapy for AWS in many intensive care units. We propose the use of symptom-triggered phenobarbital for the treatment of AWS as a safe alternative to benzodiazepines.
METHODS
This was a retrospective observational study of a 4-year period, 2011 to 2015, of all patients with AWS admitted to the MICU of 1 tertiary care hospital and treated with phenobarbital. A symptom-triggered protocol was used. Resolution of AWS was assessed with the Richmond Agitation Sedation Scale to goal score of 0 to -1. The Charlson Comorbidity Index was used as an index of patient illness severity. Complications associated with phenobarbital use and/or the AWS admission were analyzed.
RESULTS
Data of 86 AWS patient encounters were analyzed. The mean Clinical Institute Withdrawal Assessment for Alcohol-Revised score of patients admitted to the MICU with AWS was 19 ± 9. The mean phenobarbital dose administered during the MICU stay was 1977.5 ± 1531.5 mg. There were a total of 17 (20%) intubations. The most frequent cause of mechanical ventilation in patients with AWS was loss of airway clearance, followed by hemodynamic instability secondary to upper gastrointestinal bleeding and the corresponding need for endoscopy.
CONCLUSIONS
Sole use of phenobarbital use for control of AWS may be a safe alternative to benzodiazepines. Further study is needed to correlate phenobarbital serum levels with clinical control of AWS.
Topics: Adult; Alcohol-Induced Disorders; Critical Care Outcomes; Female; Humans; Hypnotics and Sedatives; Intensive Care Units; Male; Middle Aged; Phenobarbital; Respiration, Artificial; Retrospective Studies; Severity of Illness Index; Substance Withdrawal Syndrome; Treatment Outcome
PubMed: 29925291
DOI: 10.1177/0885066618783947 -
JAMA Neurology May 2024Women with epilepsy (WWE) require treatment with antiseizure medications (ASMs) during pregnancy, which may be associated with an increased risk of major congenital... (Observational Study)
Observational Study
IMPORTANCE
Women with epilepsy (WWE) require treatment with antiseizure medications (ASMs) during pregnancy, which may be associated with an increased risk of major congenital malformations (MCMs) in their offspring.
OBJECTIVE
To investigate the prevalence of MCMs after prenatal exposure to 8 commonly used ASM monotherapies and changes in MCM prevalence over time.
DESIGN, SETTING, AND PARTICIPANTS
This was a prospective, observational, longitudinal cohort study conducted from June 1999 to October 2022. Since 1999, physicians from more than 40 countries enrolled ASM-treated WWE before pregnancy outcome was known and followed up their offspring until 1 year after birth. Participants aged 14 to 55 years who were exposed to 8 of the most frequently used ASMs during pregnancy were included in this study. Data were analyzed from April to September 2023.
EXPOSURE
Maternal use of ASMs at conception.
MAIN OUTCOMES AND MEASURES
MCMs were assessed 1 year after birth by a committee blinded to type of exposure. Teratogenic outcomes across exposures were compared by random-effects logistic regression adjusting for potential confounders and prognostic factors.
RESULTS
A total of 10 121 prospective pregnancies exposed to ASM monotherapy met eligibility criteria. Of those, 9840 were exposed to the 8 most frequently used ASMs. The 9840 pregnancies occurred in 8483 women (mean [range] age, 30.1 [14.1-55.2] years). MCMs occurred in 153 of 1549 pregnancies for valproate (9.9%; 95% CI, 8.5%-11.5%), 9 of 142 for phenytoin (6.3%; 95% CI, 3.4%-11.6%), 21 of 338 for phenobarbital (6.2%; 95% CI, 4.1%-9.3%), 121 of 2255 for carbamazepine (5.4%; 95% CI, 4.5%-6.4%), 10 of 204 for topiramate (4.9%; 95% CI, 2.7%-8.8%), 110 of 3584 for lamotrigine (3.1%; 95% CI, 2.5%-3.7%), 13 of 443 for oxcarbazepine (2.9%; 95% CI, 1.7%-5.0%), and 33 of 1325 for levetiracetam (2.5%; 95% CI, 1.8%-3.5%). For valproate, phenobarbital, and carbamazepine, there was a significant increase in the prevalence of MCMs associated with increasing dose of the ASM. Overall prevalence of MCMs decreased from 6.1% (153 of 2505) during the period 1998 to 2004 to 3.7% (76 of 2054) during the period 2015 to 2022. This decrease over time was significant in univariable logistic analysis but not after adjustment for changes in ASM exposure pattern.
CONCLUSIONS AND RELEVANCE
Of all ASMs with meaningful data, the lowest prevalence of MCMs was observed in offspring exposed to levetiracetam, oxcarbazepine, and lamotrigine. Prevalence of MCMs was higher with phenytoin, valproate, carbamazepine, and phenobarbital, and dose dependent for the latter 3 ASMs. The shift in exposure pattern over time with a declining exposure to valproate and carbamazepine and greater use of lamotrigine and levetiracetam was associated with a 39% decline in prevalence of MCMs, a finding that has major public health implications.
Topics: Humans; Female; Anticonvulsants; Adult; Pregnancy; Young Adult; Adolescent; Epilepsy; Abnormalities, Drug-Induced; Middle Aged; Longitudinal Studies; Pregnancy Complications; Prospective Studies; Valproic Acid; Prenatal Exposure Delayed Effects; Phenytoin; Lamotrigine; Carbamazepine; Phenobarbital; Cohort Studies; Oxcarbazepine; Prevalence
PubMed: 38497990
DOI: 10.1001/jamaneurol.2024.0258 -
Benzodiazepines vs barbiturates for alcohol withdrawal: Analysis of 3 different treatment protocols.The American Journal of Emergency... Apr 2019Alcohol withdrawal treatment varies widely. Benzodiazepines are the standard of care, with rapid onset and long durations of action. Recent drug shortages involving IV... (Observational Study)
Observational Study
INTRODUCTION
Alcohol withdrawal treatment varies widely. Benzodiazepines are the standard of care, with rapid onset and long durations of action. Recent drug shortages involving IV benzodiazepines have required incorporation of alternative agents into treatment protocols. Phenobarbital has similar pharmacokinetics to select benzodiazepines frequently used for alcohol withdrawal. The objective of this study is to describe the effectiveness and safety of our institutional protocols during three time periods utilizing benzodiazepines and barbiturates for the acute treatment of alcohol withdrawal in the emergency department.
METHODS
Adult patients presenting to the ED for acute alcohol withdrawal from April 1st, 2016 to January 31st, 2018 were reviewed. Patients who received at least one dose of treatment were included. Treatments were based on availability of medication and given protocol at time of presentation. The primary outcome was the rate of ICU admission.
RESULTS
300 patient encounters were included. Overall baseline characteristics were equal across groups, except for age. There was no difference in rate of ICU admission from the ED between groups (D:8, L&P:11, P:13 patients, p = 0.99). Rate of mechanical ventilation was no different across all groups (D:1, L&P:3, P:3 patients, p = 0.55).
CONCLUSION
During benzodiazepine shortages, phenobarbital is a safe and effective treatment alternative for alcohol withdrawal. Incorporating phenobarbital into a benzodiazepine based protocol or as sole agent led to similar rates of ICU admission, length of stay, and need for mechanical ventilation in patients treated for alcohol withdrawal in the emergency department.
Topics: Adult; Aged; Alcohol Withdrawal Delirium; Benzodiazepines; Clinical Protocols; Colorado; Drug Therapy, Combination; Emergency Service, Hospital; Female; Humans; Length of Stay; Male; Middle Aged; Phenobarbital; Respiration, Artificial; Retrospective Studies
PubMed: 30685075
DOI: 10.1016/j.ajem.2019.01.002 -
Gastrointestinal Endoscopy Sep 2020
Topics: Esophageal Achalasia; Esophageal Sphincter, Lower; Humans; Phenobarbital; Pyloromyotomy
PubMed: 32838924
DOI: 10.1016/j.gie.2020.04.059 -
The American Journal of Emergency... Jul 2023Alcohol Withdrawal Syndrome (AWS) among patients with chronic and heavy alcohol consumption can range from mild to severe and is associated with high morbidity and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alcohol Withdrawal Syndrome (AWS) among patients with chronic and heavy alcohol consumption can range from mild to severe and is associated with high morbidity and mortality. Currently, treating AWS with benzodiazepines is the standard of care, but phenobarbital has also been hypothesized to be an effective first-line treatment due to its pharmacological properties and mechanism of action. We conducted a meta-analysis to review relevant literature and compare the clinical outcomes for patients diagnosed with AWS in ED and ICU settings.
METHODS
We performed a literature search in in the PubMed, Scopus, and Web of Science databases from inception to June 30, 2022. Randomized trials and observational (prospective or retrospective) studies were eligible if they included adult patients who presented in the ED and were treated in the ED and/or the intensive care unit (ICU) with a diagnosis of AWS. The primary outcome was the rate of intubation among patients who received phenobarbital, compared with benzodiazepines. Secondary outcomes such as rates of seizures, hospital, and ICU length of stay (LOS), also were included. The PROSPERO registration is CRD42022318862.
RESULTS
We included twelve studies (1934 patients) in our analysis. Of the 1934 patients in these studies, 765 (41.7%) were treated with phenobarbital and 1169 (58.3%) were treated with other modalities for alcohol withdrawal. Treating AWS patients with phenobarbital did not affect their risk for intubation, as the risk for intubation was similar between the phenobarbital and the control group (RR 0.70, 95% CI 0.36-1.38, P = 0.31). In addition, patients who were treated with phenobarbital were found to have similar rates of seizures (RR 0.73, 95% CI 0.29-1.89) and length of stay in the hospital (Standardized Mean Difference -0.02, 95% CI -0.26, 0.21) or the ICU (SMD -0.02, 95% CI -0.21, 0.25) when compared with patients receiving benzodiazepines.
CONCLUSIONS
Management of patients with AWS with phenobarbital is associated with similar rates of intubation, length of stay in the ICU, or length of stay in the hospital as treatment with benzodiazepines. However, due to the inclusion of mostly observational studies and a significant level of heterogeneity among the studies assessed in this review, additional trials with strong methodology are needed.
Topics: Adult; Humans; Substance Withdrawal Syndrome; Alcoholism; Retrospective Studies; Prospective Studies; Phenobarbital; Benzodiazepines; Seizures
PubMed: 37060631
DOI: 10.1016/j.ajem.2023.04.002 -
American Journal of Therapeutics
Topics: Humans; Macroglossia; Phenobarbital
PubMed: 33687030
DOI: 10.1097/MJT.0000000000001094 -
Seminars in Fetal & Neonatal Medicine Oct 2017Neonatal seizures constitute the most frequent presenting neurologic sign encountered in the neonatal intensive care unit. Despite limited efficacy and safety data,... (Review)
Review
Neonatal seizures constitute the most frequent presenting neurologic sign encountered in the neonatal intensive care unit. Despite limited efficacy and safety data, phenobarbital continues to be used near-universally as the first-line anti-seizure drug (ASD) in neonates. The choice of second-line ASDs varies by provider and institution, and is still not supported by sufficient scientific evidence. In this review, we discuss the available evidence supporting the efficacy, mechanism of action, potential adverse effects, key pharmacokinetic characteristics such as interaction with therapeutic hypothermia, logistical issues, and rationale for use of neonatal ASDs. We describe the widely used neonatal ASDs, namely phenobarbital, phenytoin, midazolam, and levetiracetam, in addition to potential ASDs, including lidocaine, topiramate, and bumetanide.
Topics: Anticonvulsants; Fructose; Humans; Hypothermia, Induced; Infant, Newborn; Lidocaine; Midazolam; Phenobarbital; Seizures; Topiramate; Treatment Outcome
PubMed: 28811085
DOI: 10.1016/j.siny.2017.07.008