Serum Levels Of Phenobarbital Research Articles

Caracterização da conduta clínica no atendimento e tratamento de cães com crises epilépticas

ABSTRACT: This survey analyzed data obtained through a questionnaire on the clinical approaches used by veterinarians to treat dogs with epileptic seizures. We found that neurological examinations were performed by 12% of the respondents, blood tests by 85%, and computed tomography by 72%. In addition, serology for infectious disease detection was mentioned by 30% of the respondents, and 72% did not classify epileptic seizures. According to the answers, the treatment of choice was phenobarbital in 100% of cases which was combined with potassium bromide in 19%. Moreover, 51% of the respondents mentioned that they monitored the serum phenobarbital levels. The study results showed disagreements on the conduct and care recommended by the International Veterinary Epilepsy Task Force consensus.

Front-Loaded Versus Low-Intermittent Phenobarbital Dosing for Benzodiazepine-Resistant Severe Alcohol Withdrawal Syndrome.

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. 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 (260mg intravenous push × 1 followed by 130mg intravenous push every 15min as needed) from January2013 to July 2015, and front-loaded phenobarbital doses (10mg/kg intravenous infusion over 30min) from July 2015 to January 2017. In total, 87 patients met inclusion criteria for this study:41received low-intermittentphenobarbital and 46 receivedfront-loadedphenobarbital). 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 86mg [IQR 24-197] vs. 228mg [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. 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.

Laboratory Evaluation and Serum Level of Phenobarbital Administered by Different Pathways in Dogs

Background: Anticonvulsants are widely used in the treatment of small animals for the remission of isolated seizures and recurrent seizures in epilepsy, including tonic-clonic seizures and in status epileticus. Phenobarbital is the drug of choice for the management of epileptic seizures, it is considered very effective, safe, low cost and with few side effects. Several routes of administration may be used, with the oral, intravenous and intramuscular routes being the most common, with rectal and nasal routes being the least common. Materials, Methods &amp; Results: Twenty mongrel dogs were used in the present study (aged 1 to 6-year-old, males and females, weighing 6.0 to 17.0 kg). The patients were previously evaluated via physical examination, temperature, respiratory and heart rate, laboratory tests (erythrogram and leukogram), and serum biochemistry by analyzing the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (FA), and gamma-glutamyltransferase (GGT). Four experimental groups were established with five animals in each group: animals receiving intramuscular injections of phenobarbital (VIM), animals receiving nasal administration of phenobarbital (VN), animals receiving rectal administration of phenobarbital (VR), and animals receiving oral administration of phenobarbital (VO). Phenobarbital was administered every 12 h for 15 days. To determine the serum level of phenobarbital, 5 mL of jugular vein blood was collected in vacuum tubes for evaluation via hemogram. The serum level was determined after 15 days of continuous administration of phenobarbital, as stable phenobarbital serum levels can only be achieved from 10 to 15 days after the first administration. For the serum biochemistry evaluation, 10 mL of blood from the jugular vein was collected using vacuum syringes for assessing ALT, AST, GGT, and FA levels. Statistical analyses were performed with contrasted variation analysis using the Tukey method and paired t-test for comparison of time points. The level of significance was determined to be 5%. There was a significant difference (P &lt; 0.05) among drug administration routes, and among the levels of AST and AF enzymes after the first administration of phenobarbital via the nasal and intramuscular routes. Based on the results, it was concluded that hepatic alterations secondary to the use of phenobarbital for 15 days may occur with a low incidence. The phenobarbital serum concentration in dogs varied when administered via nasal, rectal, and intramuscular routes, but was stable when administered orally.Discussion: The current results are consistent with those of previous studies, indicating that the chronic use of phenobarbital causes an increase in the serum levels of ALT and FA enzymes. It was found that phenobarbital serum levels varied greatly, particularly following nasal, rectal, and intramuscular administration. In the present study, serum phenobarbital levels were within the normal range when administered via the intramuscular, nasal, rectal, and oral routes. This result is inconsistent with that of previous studies where the serum levels were below the normal range following oral administration of phenobarbital. The serum concentration, rather than clinical criteria, should be used as a guide for treatment modification, as the distribution of this drug varies greatly among animals.

The Safety and Utility of Phenobarbital Use for the Treatment of Severe Alcohol Withdrawal Syndrome in the Medical Intensive Care Unit.

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. 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. 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. 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.

Phenobarbital – a beneficial eight-hourly dosing option?

IDIOPATHIC epilepsy is the most common neurological medical condition in dogs with an estimated prevalence of 0.6 per cent presenting to first-opinion practice in the UK (Kearsley-Fleet and others 2013)....

Phenobarbital administration every eight hours: improvement of seizure management in idiopathic epileptic dogs with decreased phenobarbital elimination half-life

Estimated prevalence of canine idiopathic epilepsy is 0.6 per cent in the first-opinion canine population in the UK. Phenobarbital monotherapy has been reported to reduce/eradicate seizure activity in 60–93 per...

Diagnostic evaluation and treatment of a Chinese crocodile lizard (Shinisaurus crocodilurus) with seizures

An 11-year-old female Chinese crocodile lizard (Shinisaurus crocodilurus) with presumed seizures was examined. Complete blood count, plasma biochemistry and MRI did not identify a cause of seizures and thus cryptogenic...

Mega-dose phenobarbital therapy for super-refractory status epilepticus.

To evaluate the efficacy and safety of mega-dose phenobarbital (MDPB; enteral or parenteral phenobarbital >10 mg/kg/day) for treating super-refractory status epilepticus (SRSE; continuous or recurrent status epilepticus for ≥24 hours after the onset of continuous anaesthetic treatment) in adult patients. Adult patients with SRSE who were treated with MDPB in our institution from March 2005 to September 2014 were reviewed. We collected data on basic demographics, clinical features, functional status, anticonvulsant treatment, and possible adverse events. SRSE outcome was divided into six categories: successful therapy, initial failure, breakthrough seizures, withdrawal seizures, intolerable side effects, and death during treatment. Ten adult patients with SRSE received MDPB. Median age at seizure onset was 38 years (range: 18-59), and half were male. All patients had no history of seizures and had symptoms suggestive of viral encephalitis. Median duration of status epilepticus was 17.5 days (range: 6-60) and anaesthetics were used for a median of 14.0 days (range: 2-54) before MDPB. Successful control of SRSE was achieved in half of the patients, however, only one of ten patients was able to fully recover at discharge. Median duration of the MDPB was 45.5 days and the maximum serum phenobarbital level reached a median of 151.5 μg/ml. Patients with successful MDPB therapy had normal brain imaging (80% vs. 0%; p=0.048) and better functional outcome at discharge and after three months of follow-up. Infection was the most critical complication, along with cardiorespiratory depression. MDPB is a therapeutic option for control of SRSE when other choices are exhausted.

Efficacy and tolerability of high-dose phenobarbital in children with focal seizures

ObjectiveWe retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. MethodsWe reviewed data on children (aged<15years) with focal seizures treated with high-dose phenobarbital (>5mg/kg/day to maintain a target serum level >40μg/mL) for at least 6months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. ResultsSeven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30months. The maximal serum phenobarbital level ranged from 36.5 to 62.9μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. ConclusionOral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult.

Safety of Phenobarbital Use for Alcohol Withdrawal Syndrome in the Medical Intensive Care Unit

SESSION TITLE: Critical Care Posters I SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: 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 a first line therapy for AWS in many intensive care units. We propose that the use of symptom triggered phenobarbital for the treatment of AWS is a safe alternative to benzodiazepines. METHODS: This was a retrospective chart review of a three year period, 2011 to 2014, of all MICU alcohol withdrawal syndrome admissions in whom phenobarbital levels were drawn. Hospital and MICU length of stay, total phenobarbital dose administered, and phenobarbital serum levels were analyzed. Resolution of alcohol withdrawal syndrome was assessed with the Richmond Agitation Sedation Scale (RASS) to goal score of 0 to -1. Severe AWS was defined as a CIWA score greater than 15 prior to MICU assessment and consideration for admission. Complications associated with the AWS admission were recorded. The Charlson Comorbidity Index (CCI) was used as an index of patient illness severity. RESULTS: Data of 40 patients with 45 MICU admissions for AWS was analyzed. The average total phenobarbital dose during the MICU stay was 2131 milligrams. The average CCI was 1.14. The average hospital length of stay was 8.4 days and the average length of MICU stay was 3.89 days. The average phenobarbital serum level was 33.71. There were 4 intubations out of the 45 separate admissions secondary to benzodiazepines administered prior to MICU admission. No patients were intubated secondary to phenobarbital use. One patient was treated for a urinary tract infection; 1 was treated for alcohol associated pancreatitis; 1 was treated for aspiration pneumonia. None of the analyzed patients required an alternative agent for AWS control post MICU stay when phenobarbital was used. CONCLUSIONS: Sole use of phenobarbital use for control of alcohol withdrawal syndrome may be a safe alternative to benzodiazepines. Further study is needed to correlate phenobarbital serum levels and clinical control of AWS. CLINICAL IMPLICATIONS: Phenobarbital may be a suitable substitute in the treatment of severe alcohol withdrawal syndrome necessitating intensive care unit admission. DISCLOSURE: The following authors have nothing to disclose: Krystal Cleven, lauren healy, Mabel Wei, Seth Koenig, Paul Mayo, Mangala Narasimhan, Margarita Oks No Product/Research Disclosure Information

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.

Urine Phenobarbital Drug Screening

This study was done to determine if urine phenobarbital measurements provide a reliable indicator of presence of the drug in neonates. Urine was collected from neonates treated with phenobarbital for clinical indications within 4 to 6 hours of clinically indicated collection of serum phenobarbital levels. Urine samples were also collected from control neonates not treated with phenobarbital. One aliquot was assayed fresh, another frozen at -30°C and assayed 1 to 3 months later. Phenobarbital was assayed using the ONLINE TDM Roche/Hitachi automated clinical chemistry analyzer. Serum and urine concentrations were compared as were fresh and frozen urine measurements. Serum phenobarbital ranged from 5.6 to 52.7 μg/mL. Matched urine samples were 56.6 ± 12.5% of the serum level. Frozen samples were 98.3 ± 8.0% of the fresh samples. Urine phenobarbital concentrations, either fresh or frozen, can be used in neonates as a noninvasive estimate of drug levels.

English

To investigate the safety and side effects of prolonged treatment with high-dose phenobarbital in patients suffering from acute encephalitis with refractory, repetitive partial seizures (AERRPS), 5 AERRPS patients meeting the Sakuma&rsquo;s criteria were recruited from July 2003 to September 2008. During the treatment with high-dose phenobarbital, the blood pressure, heart rate, cardiac rhythm, respiratory rate, blood gas, skin conditions, state of consciousness, pupil size, seizures and long-range electroencephalogram were monitored. After intravenous bolus injection of phenobarbital (200 mg) or intramuscular infection of phenobarbital for induction, and then phenobarbital was intravenously administrated at 1 to 1.5 mg/kg/h or intramuscularly given (200 mg) (or intravenous bolus injection) q 2 to 4 h to maintain plasma concentrations. The daily overall dose of phenobarbital was 1.2 to 2.4 g. The serum level of phenobarbital reached 100 &mu;g/ml within 24 h and remained for 24 d to 100 d. Follow up was carried out for at least 6 months. During the treatment of high dose phenobarbital, these 5 patients were in coma and the scores of Glasgow coma scale were 3 to 5. The brainstem reflex was mostly preserved and the spontaneous breathing was absent. The side effects in the circulation system included arrhythmia and hypotension. Sinus tachycardia (n = 3) and ventricular/supraventricular tachycardia (n = 2) were controlled by amiodarone, and the blood pressure was decreased by 40 to 55/64 to 86 mmHg (n = 2) which resolved after dopamine treatment (5 to 10 &mu;g/kg/min). Liver injury was evident and observed in all 5 patients. The serum levels of alanine aminotransferase, aspartate aminotransferase and &gamma; glutamyl transferase was 57 to 385 IU/L, 38 to 365 IU/L and 54 to 542 IU/L, respectively. The maximal level of serum ammonia was 187 &mu;g/dl. No yellow skin was observed, and the serum levels of direct and indirect bilirubin were normal. Skin reaction was mild and kidney function almost intact. When the serum level of phenobarbital was decreased to 50 &mu;g/ml, the consciousness and spontaneous breathing recovered and side effects were nearly absent. It is indicated that severe side effects may occur during prolonged treatment with high-dose phenobarbital. When this strategy is necessary, assisted ventilation is recommended and side effects should be closely monitored. &nbsp; Key words:&nbsp;Encephalitis, status epilepticus, phenobarbital, side effect. safety.

Infants born to mothers under phenobarbital treatment: correlation between serum levels and clinical features of neonates

ObjectivePhenobarbital crosses the placenta quickly, and the balance between maternal and fetal blood is achieved in a few minutes. Data on the clinical outcomes of infants born to mothers under phenobarbital treatment during pregnancy show that they are at risk of adverse events, such as sedation and abstinence syndrome. The aim of this study was to analyse the correlation between serum levels of phenobarbital and clinical features of neonates. Study designTwenty-three infants born between 2001 and 2008 were studied. Maternal, neonatal and pharmacological variables were considered. ResultsEleven infants displayed symptoms related to phenobarbital. Withdrawal syndrome was seen in seven infants and sedation syndrome was seen in four infants. One infant had severe cardiorespiratory depression at birth. None of the infants had severe neonatal abstinence syndrome. No statistically significant differences were found between symptomatic and asymptomatic infants. At birth, the mean serum level of phenobarbital of the 23 infants was 15.4 [standard deviation (SD) 6.2]μg/ml. A peak (16.1μg/ml, SD 5.5) was seen on Day 3, followed by a gradual decrease to non-therapeutic levels (<10μg/ml) by Day 8 (9.3μg/ml, SD 1.0). Phenobarbital levels were higher in symptomatic infants than asymptomatic infants, although the difference was not statistically significant. ConclusionsSerum levels of phenobarbital remained in the therapeutic range for both mothers and infants, and reduced gradually in infants. However, some infants displayed symptoms related to phenobarbital. As such, a clinical pharmacological surveillance protocol is necessary.

小児におけるPhenobarbitalとCarbamazepineの血中濃度, ならびに, 熱性痙攣と全身痙攣型てんかんにおける有効血中濃度の検討

小児におけるPhenobarbitalとCarbamazepineの血中濃度, ならびに, 熱性痙攣と全身痙攣型てんかんにおける有効血中濃度の検討

Single Enteral Loading Dose of Phenobarbital for Achieving Its Therapeutic Serum Levels in Neonates

To investigate whether therapeutic serum drug levels may be achieved with a single enteral loading dose of phenobarbital. The study was performed at the Mersin University Hospital in Turkey between April 2004 and August 2006, and included 29 newborn babies with seizure. After the acute treatment of the seizure with midazolam at a dose of 0.1 mg/kg, phenobarbital was administered by orogastric route at a loading dose of 20 mg/kg. Serum phenobarbital concentrations were measured at 0.5, 3, 6, and 12 hours after the loading. Serum phenobarbital levels between 10-30 microg/mL were considered as the therapeutic range. The serum phenobarbital levels reached therapeutic values in 9 (31%), 19 (66%), 21 (72%), and 23 (79%) patients at 0.5, 3, 6, and 12 hours after loading, respectively, while they did not reach therapeutic values in 6 patients (21%) after 12 hours. Four of the patients in whom there was no increase in serum phenobarbital levels had hypoxic-ischemic encephalopathy. Enteral loading of phenobarbital can achieve therapeutic serum levels in the large majority of newborn babies with seizure and may be safely used in babies with the intact gastrointestinal tract.

Transient leucopenia, thrombocytopenia and anaemia associated with severe acute phenobarbital intoxication in a dog

A nine-year-old Labrador retriever dog was admitted to the emergency unit of the Hebrew University Veterinary Teaching Hospital with acute-onset tremors and coma. It had recently ingested a large quantity of phenobarbital and had a high serum phenobarbital concentration. On this basis, a diagnosis of acute phenobarbital intoxication was made. Significant leucopenia, thrombocytopenia and mild anaemia developed on the third day after admission. The leucopenia resolved on day 6 and the thrombocytopenia on day 13. The red blood cell count remained low for the next month. The dog was discharged on day 13 at which time it was ambulatory but weak. It was completely recovered clinically eight days later. In summary, high levels of serum phenobarbital as a result of acute intoxication induced pancytopenia, which improved when the serum phenobarbital level was normalised.

Neonatal Seizures: Multicenter Variability in Current Treatment Practices

Standardized approaches to the treatment of neonatal seizures remain undeveloped. We assessed the type and number of anticonvulsants selected, blood levels attained, and postdischarge anticonvulsant treatment of neonatal seizures among five neonatal intensive care units in the United States between 2000-2003. Almost all of the 480 neonates (94%) with seizures were treated, initially with phenobarbital (82%), lorazepam (9%), phenytoin (2%), other anticonvulsants (1%), or a combination of the first two drugs (6%). While the majority of neonates were treated with one drug (59%), the number of anticonvulsants varied (P<0.0001), as did the peak serum phenobarbital levels (P<0.0001). The majority (75%) of survivors received anticonvulsant treatment after discharge. These neonates were more likely to have had abnormal electroencephalography or brain imaging, or to have needed a second anticonvulsant, compared with neonates whose drug therapy was discontinued. Anticonvulsant therapy is used in the majority of neonates with seizures, mostly with phenobarbital, and treatment is continued beyond discharge. The observed wide therapeutic variability may reflect a lack of standardized diagnostic and treatment approaches, particularly for seizures refractory to initial phenobarbital therapy. Trials of anticonvulsants with long-term neurodevelopmental follow-up are needed to develop evidence-based treatment guidelines.

Evaluation of therapeutic drug level monitoring of phenobarbital, phenytoin and carbamazepine in Iranian epileptic patients

The antiepileptic drugs phenobarbital, phenytoin and carbamazepine are widely used for the treatment of partial and tonic-clonic seizures. Large inter-individual differences in pharmacokinetics of these drugs, and the intermittent nature of epileptic attacks, increase the need for therapeutic drug level monitoring of these drugs. In this study, data from the therapeutic drug monitoring of phenobarbital, carbamazepine and phenytoin in 328 epileptic patients were evaluated. Serum levels of drugs were determined in a University Department of Pharmacology by high-performance liquid chromatography. In this study, approximately 56% of patients were treated with 1; 30% with 2; and 14% with 3 antiepileptic drugs. In patients receiving 1 antiepileptic drug, the percentages treated with phenobarbital, carbamazepine and phenytoin were 41, 38 and 21%, respectively. In patients who received carbamazepine, serum levels in 40% of the patients were in the range of 4-8 microg/ml and more than in the range 4-12 microg/ml in 74% of the patients. In phenobarbital-treated patients, serum levels in 73% of the patients were in therapeutic range of 10-40 microg/ml, and about 44% of phenytoin-treated patients had serum levels in therapeutic range of 10-20 microg/ml. Approximately 50% of carbamazepine- and phenytoin-treated patients and approximately 70% of phenobarbital-treated patients were completely controlled. The frequency of concentrations within the therapeutic ranges decreased in patients using more than 1 antiepileptic drug. In patients who received both phenobarbital and sodium valproate, serum levels of phenobarbital were significantly (p < 0.05) greater than in patients who were taking this drug in combination with carbamazepine or phenytoin. Our results indicate that serum levels of antiepileptic drugs, and the percentage of patients with complete seizure control are comparable with results obtained in other populations in previous studies.

Oral high-dose phenobarbital therapy for early infantile epileptic encephalopathy

We report oral high-dose phenobarbital therapy for a patient with early infantile epileptic encephalopathy with suppression bursts (Ohtahara syndrome). At 1 month of age, many series of tonic spasms, with raising limbs and crying lasting for a few minutes, developed and increased up to approximately 300 times per day. Initially intravenous midazolam (0.5 mg/kg/hour) slightly decreased the seizures, although oral vitamin B6, valproic acid, clonazepam, and zonisamide had little effect. Oral high-dose phenobarbital therapy was begun at a dosage of 15 mg/kg/day, and the seizures markedly decreased to 5–10 times per day and the epileptic discharges on electroencephalogram greatly decreased. Serum phenobarbital levels ranged between 60 and 100 mg/dL. High-dose phenobarbital therapy should be considered for the treatment of early infantile epileptic encephalopathy with suppression bursts.