Phenobarbital In Patients Research Articles

Effect of Phenobarbital-Based Alcohol Withdrawal Protocol on Provider Practice and Patient Outcomes-A Quality Improvement Study.

Introduction: Alcohol is the most common substance use disorder in the United States. Despite this prevalence, there remains significant heterogeneity in medical management of alcohol withdrawal syndrome (AWS). While the 2020 American Society of Addition Medicine continues to recommend the use of benzodiazepines as first-line therapy for AWS, there is increasing use of phenobarbital in patients at high risk of severe AWS. Despite phenobarbital's favorable pharmacologic profile, historically, clinical utilization on general medicine services has been low and often restricted. In this project, we have examined practice patterns and associated clinical outcomes in adult patients experiencing AWS on the general medicine service pre and post implementation of a phenobarbital-based protocol for the treatment of severe AWS at our institution. Methods: This quality improvement study evaluated changes in management of AWS on general medicine units associated with implementation of a phenobarbital-based protocol and order set in the electronic medical record (EMR). Our primary outcome measures were receipt of a phenobarbital loading dose, concomitant benzodiazepine administration, and total benzodiazepine dose. Safety outcomes were also explored to assess clinical impacts of this protocol implementation. The project was determined "not research" by our Institutional Review Board. Results: Phenobarbital-protocol implementation was associated with increased frequency of receiving a phenobarbital loading dose (49.5% vs 9.4%; P < .001), decreased use of concomitant benzodiazepine/phenobarbital (4.3% vs 28.9%; P < .001), and decreased total benzodiazepine dose (7.8 vs 15.5 mg; P < .001). Regarding safety, there was no significant pre/post difference in the rate of ICU transfer, but among those transferred there was a trend toward decreased mechanical ventilation rate (100% vs 28.6%; P = .051), and a significantly reduced ICU length of stay (median 11 vs 3 days; P = .04). There were no pre/post differences in seizures, delirium or use of adjunct medications. Conclusions: This quality improvement study demonstrates a marked change in provider prescribing practices for treating AWS after implementation of an institutional phenobarbital-based protocol. We observed no difference in overall clinical outcomes after protocol implementation, although a larger follow-up study is needed to confirm this and to further explore the shorter ICU length of stay for patients with AWS postimplementation.

Autonomic dysregulation and phenobarbital in patients with masked primary hypertension

IntroductionPrimary hypertension can be masked and be responsible of a severe impact on the target bodies. The purpose of this study was to see if Phenobarbital at low dose is able to decrease the sympathetic hyperactivity assessed by cardiovascular autonomic reflexes in patients with masked hypertension. Materials and methodsThis prospective study was conducted on a total of 91 patients with masked hypertension (average age 52.1 ± 10.3 years old). The cardiovascular autonomic tests performed in this group, before and after 3 months of daily oral administration of Phenobarbital, included deep breathing, hand-grip, mental stress and orthostatic tests. Statistical analysis was done using the Student's t-test, Univariate and Multivariate logistic regression analysis; p is significant if < 0.05. ResultsCardiovascular autonomic reflexes responses before and after 3 months of Phenobarbital oral administration were as follows: Vagal response (XDB) obtained on deep breathing test was of 32.6 ± 5.4% VS 30.4 ± 6.1%, (p = 0.08), alpha peripheral sympathetic response (alpha SP) obtained on hand grip test was of 35.6 ± 8.7% VS 12.0 ± 2.5%, (p < 0.001), alpha central sympathetic response (alpha SC), beta central sympathetic response (beta SC) obtained during mental stress were of respectively 29.3 ± 9.2% VS 11.8 ± 2.4%, (p < 0.001) and 11.0 ± 5.3% VS 10.4 ± 6.1%, (p = 0.2), alpha peripheral adrenergic sympathetic (alpha PAS) obtained during orthostatic test was of 25.3 ± 6.0% VS 13.0 ± 3.4%, (p < 0.001). ConclusionThese results demonstrated that Phenobarbital at low dose may have an anti-sympathetic effect in patients with masked hypertension.

Cost-Effectiveness Analysis of Topiramate versus Phenobarbital in the Treatment of Children with Febrile Seizure.

Febrile seizure is common disorder in childhood, with a prevalence of 2% to 5%. There are many drugs for treatment of this disease; however, the most common prescribed medication in Iran is phenobarbital that is cheap, but it has many side effects. We aimed to compare the cost-effectiveness of topiramate versus phenobarbital in patients with febrile seizure in the south of Iran. This econometric cost-effectiveness and cost-utility study were conducted on 91 patients with febrile seizure to assess two strategies of oral drug therapy including phenobarbital and topiramate in 2016-2017. Of all, 51 patients were treated with phenobarbital and 40 patients received topiramate. We followed up the patients for six months, using a randomized and single-blinded approach. A decision tree model was used. The outcomes of the model included febrile seizure and utility. The study was conducted from the perspective of the community; therefore, direct and indirect costs were included in the study. Excel and Tree Age software (2011) were used to analyze the results. Topiramate was cheaper and more effective than phenobarbital. In patients in the phenobarbital and topiramate groups, the mean costs were $740 and $674 per PPP, utility scores were 0.72 and 0.82, and febrile seizure without side effects were 0.3 and 0.6, respectively. Moreover, one-way sensitivity analysis confirmed the robustness of the results of the study. Topiramate in patients with febrile seizure is a fully cost-effective and cost-efficient strategy suggested as a better alternative for children with febrile seizure.

The effectiveness of phenobarbital in patients with refractory status epilepticus undergoing therapeutic plasma exchange.

This study aimed to elucidate the therapeutic concentration range of phenobarbital (PB) for adults, as well as the influence of therapeutic plasma exchange (TPE) on plasma concentration of PB. We retrospectively reviewed consecutive patients diagnosed with refractory status epileptic (RSE) and treated with a bolus injection of PB as well as TPE, admitted to our neurocritical care unit from November 2015 to October 2016. Continuous electroencephalographic monitoring was performed routinely for these patients. TPE was performed using a continuous-flow cell separator. PB concentrations in the plasma and cerebrospinal fluid were measured by gas chromatography-mass spectrometer analysis before and after TPE. A total of seven patients were included; among these, one patient had RSE related to anti-N-methyl-D-aspartate receptor encephalitis, another patient had Hashimoto encephalopathy, and five patients had undetermined etiology. For patients with clinical and electrographic control (n=6), the plasma concentration of PB ranged from 138 to 243.7 μg/ml. In addition, of six paired plasma samples (before and after TPE) obtained from three patients, no significant differences between the concentrations of PB were detected (P=0.6), suggesting that TPE may not significantly affect the plasma concentration of PB. This study confirmed that PB more than 100 µg/ml was effective for adults with RSE. Moreover, TPE may not have an influence on the plasma concentration of PB.Video abstract: http://links.lww.com/WNR/A489.

Serum Total Antioxidant Capacity of Epileptic Children before and after Monotherapy with Sodium Valproate, Carbamazepine, and Phenobarbital.

This case-control study was carried out to compare serum total antioxidant capacity (TAC) in the newly diagnosed children with epilepsy and that of a control group of healthy children at the same age and probable effects of antiepileptic drugs (AEDs) prescription on it. Overall, 130 participants (65 in each group) aged between 1 and 17 yr old were enrolled. The study was conducted in Children's Medical Center, the Pediatrics Center of Excellence, Tehran, Iran in 2010. Serum TAC test was done for both control and patients group before AED therapy and after 3 months of monotherapy with sodium valproate, carbamazepine and phenobarbital in patients. Serum TAC values were measured based on Erel's method using an automated commercial kit. This method is based on the bleaching of the characteristic color of a more stable 2, 2'azinobis (3ethylbenzothiazoline6sulfonicacid) radical cation by antioxidants. The results were expressed in mmol Trolox equivalent/l. Serum TAC values were significantly lower in the patients group before drug administration [mean (SD): 1.31 (0.19) mmol/L] in comparison with the control group [mean (SD): 1.46 (0.21) mmol/L] (P<0.001). In the patient's group, no differences were found in the serum TAC before and 3 months after AED monotherapy. Reduced serum TAC and an increased vulnerability to oxidative stress should be considered as an etiologic factor in the children with epilepsy.

Free-to-Bound Serum Phenobarbital Levels in Dogs

Monitoring phenobarbital levels in dogs has not traditionally taken free-to-bound serum phenobarbital levels into consideration. This study was designed to evaluate free-to-bound phenobarbital in healthy research dogs during the initiation of therapy with phenobarbital. These findings were compared with the levels obtained during routine therapeutic monitoring of phenobarbital in epileptic dogs. This appears to be the first descriptive study which has looked at free-to-bound phenobarbital in clinical canine patients. During the first week of therapy in healthy canine subjects, the free-to-bound ratio was 0.7 due to the high degree of protein-binding of serum phenobarbital. This was in contrast to the level of protein-binding in epileptic patients receiving phenobarbital chronically, with a free-to-bound ratio of 3.0 ± 2.7. Moreover, during the initiation of therapy with phenobarbital, some of the bound fraction could be displaced with sulfadimethoxine indicating that free-to-bound phenobarbital may have significance during this period. On the other hand, chronic therapy in epileptic dogs leads to reduction in the bound fraction for serum phenobarbital. This leads to a strong, direct correlation of total and free phenobarbital in these patients. This relationship is consistent over a wide range of serum concentrations and does not appear to be affected by the age of the patient, the length of chronic therapy or the presence of other anticonvulsant medications. There was an inverse relationship with total plasma proteins and free phenobarbital concentrations, but it was not statistically significant. Routine monitoring of free-to-bound phenobarbital may not be warranted except under specific conditions.

Levetiracetam, lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer’s disease

The objective of the study described here was to evaluate the efficacy, tolerability, and cognitive effects of levetiracetam (LEV) in patients with seizures and Alzheimer’s disease (AD). This was a prospective, randomized, three-arm parallel-group, case–control study of 95 patients taking LEV (n=38), phenobarbital (PB) (n=28), and lamotrigine (LTG) (n=29). A 4-week dose adjustment was followed by a 12-month evaluation period. The three groups were compared to a control group (n=68) to evaluate cognitive effects of the antiepileptic drugs. We examined drug effects cross-sectionally at baseline, 6months, and 12months. There were no significant differences in efficacy among the three AEDs. LEV caused fewer adverse events than the other AEDs. PB produced persistent negative cognitive side effects. LEV was associated with improved cognitive performance, specifically attention level and oral fluency items. LTG had a better effect on mood. LEV had a benign neuropsychological side effect profile, making it a cognitively safe drug to use for controlling established seizures in elderly patients with Alzheimer’s disease.

Phenobarbital Treatment in a Patient with Resistant Alcohol Withdrawal Syndrome

Alcohol withdrawal syndrome (AWS) is a major cause of morbidity and mortality in the acute care setting. We describe a 28-year-old man who was brought to the emergency department with a new-onset seizure and clinical signs and symptoms consistent with advanced delirium tremens. A symptom-triggered intensive care unit treatment protocol consisting of a benzodiazepine and antiadrenergic agents was started. The manifestations of delirium tremens persisted with titration of a lorazepam infusion in excess of 40 mg/hour. Intravenous phenobarbital was administered in escalating doses of 65 mg followed by 130 mg 15 minutes later, resulting in control of severe agitation in the face of benzodiazepine resistance. Subsequent scheduled phenobarbital administration allowed for a successful and orderly weaning of the continuous benzodiazepine infusion and adjunctive agents used in AWS management. With continued clearing of consciousness, the patient was successfully discharged. The administration of phenobarbital in this patient allowed improved symptom control, minimized the potential for propylene glycol toxicity, was not associated with respiratory depression, and facilitated successful weaning of benzodiazepines. Barbiturates offer a mechanism of action that is different from that of benzodiazepines. Although the cornerstone of treatment for AWS remains benzodiazepines, this case highlights the potential utility of phenobarbital in patients with resistant AWS.

Risk factors for status epilepticus in children with symptomatic epilepsy.

The purpose of this study was to determine risk factors for status epilepticus (SE) in children with symptomatic epilepsy through a retrospective case-control study. Patients (44 children with a prior diagnosis of symptomatic epilepsy experiencing one or more episodes of SE between January 1, 1991, and June 1, 1995) were matched for age at follow-up to controls (88 children with symptomatic epilepsy without SE during that interval) and medical records were reviewed. Patients and controls did not differ in etiology or in age at epilepsy onset (1 year 5 months [SD, 2 years 3 months] versus 1 year 3 months [SD, 1 year 5 months]). Univariate analysis revealed significant associations between SE and several factors, including history of a first seizure as SE, partial epilepsy, partial seizures with secondary generalization, focal paroxysmal abnormalities and focal background abnormalities on EEG, and generalized abnormalities on neuroimaging. Groups did not differ in the proportion of patients on polypharmacy or with subtherapeutic serum antiepileptic drug levels, but there was a trend for greater use of phenobarbital in patients (57% versus 38%, odds ratio (OR) = 2.6, p = 0.057). With multiple logistic regression, four factors emerged as independent predictors of SE risk: focal background EEG abnormalities (OR = 6.51, p = 0.0005), partial seizures with secondary generalization (OR = 4.61, p = 0.0021), first seizure as SE (OR = 3.99, p = 0.034), and generalized abnormalities on neuroimaging (OR = 2.85, p = 0.034). These four factors are indicators of a higher risk of SE in children with symptomatic epilepsy.

Diagnosis and treatment of phenobarbital in patients with Gilbert's syndrome

Until now, the diagnosis of unconjugated hyperbilirubinemia presents certain difficulties, which is to a certain extent related to the lack of awareness among doctors of a wide medical network [1, 2, 4, 8].