Loading Dose Of Phenobarbital 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.

Phenobarbital as Anticonvulsant Prophylaxis in Patients With Traumatic Brain Injury at Risk for Alcohol Withdrawal Syndrome.

Background: Anticonvulsant prophylaxis (ACP) for early post-traumatic seizures (PTS) is recommended in patients with traumatic brain injury (TBI). Phenobarbital (PB) may be used to prevent alcohol withdrawal syndrome (AWS) in at-risk patients. The dual-purpose use of PB in the TBI population would allow for consolidation of pharmacotherapy. Objective: The primary objective of this study was to determine the frequency of early PTS in TBI patients at risk of AWS treated with PB as ACP. Secondary objectives included determining rates of over sedation and endotracheal intubation. Methods: Patients received an intravenous (IV) loading dose of PB at 15-20mg/kg followed by 1mg/kg every 12hours for 7days with a goal level of 15-20mcg/mL. Medication data, seizure frequency, and episodes of over sedation and endotracheal intubation were collected. Results: Eighty patients were treated with PB over a 1-year period. Thirty-nine patients were analyzed. Median loading dose was 19.9 (Interquartile Range 19.1-20.0) mg/kg with a median post load level of 21.7mcg/mL (IQR 18.3-25.8) mcg/mL. One patient (2.6%) had electrographic evidence for early PTS. PB was discontinued in 4 (10.3%) patients out of concern for over sedation. One patient required endotracheal intubation after rapid PB loading. Conclusion: The frequency of early PTS was low when PB was used as primary ACP in patients with TBI at risk for AWS. Over sedation is a potential adverse effect that should be considered in the choice of ACP. No conclusions can be drawn as to the effectiveness of PB in preventing AWS.

Oral Loading of Phenobarbital to Achieve Therapeutic Effects in Pediatric Patients with Acute Repetitive Seizures

Purpose: Intravenous phenobarbital has not been available at our institution since 2019. This study aimed to determine the effectiveness of oral phenobarbital loading at a dose of 15 to 20 mg/kg to achieve therapeutic serum levels and clinical seizure control in pediatric patients with acute repetitive seizures.Methods: This is a retrospective single-center review of the medical records of pediatric patients admitted for acute repetitive seizures (from January 2019 to June 2022) at the Philippine Children’s Medical Center who were given an oral phenobarbital loading dose of 15 to 20 mg/kg with serum level measurements taken within 48 hours after oral loading. Results: Eleven patients were given a single oral phenobarbital loading dose of 15 to 20 mg/kg, while 14 were given two doses of 10 mg/kg 12 hours apart. All 25 patients achieved therapeutic serum levels within 48 hours post-loading. Higher serum levels were seen at 48 hours (median, 19.8 μg/mL at 24 hours vs. 24.4 μg/mL at 48 hours). This difference was statistically significant at 5% (P=0.023), and the majority achieved adequate seizure control without requiring additional anti-seizure medications (76%). Transient drowsiness was the most commonly documented adverse effect. Conclusion: Oral loading of phenobarbital at a dose of 15 to 20 mg/kg given as a single dose or in two divided doses is an effective and safe alternative to achieve therapeutic serum levels and adequate clinical seizure control at 24 hours post-loading. This may be a promising and useful intervention at centers without available intravenous phenobarbital.

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

The Use of a Single Dose of Phenobarbital for Inpatient Management of Benzodiazepine Withdrawal: A Case Report.

The current standard of care for physiological dependence to benzodiazepines requires prolonged outpatient tapers, which present challenges for patients and providers. Novel protocols for accelerated benzodiazepine tapers are needed. We describe a case of successful management of benzodiazepine withdrawal in the inpatient setting using a single, loading dose of phenobarbital with adjunctive valproate therapy. A 61-year-old woman with benzodiazepine use disorder using 3 to 4 mg of alprazolam daily presented to an inpatient medically supervised withdrawal unit requesting discontinuation of all benzodiazepines and other recreational substances by the time of discharge. Benzodiazepine withdrawal was treated with a single, loading dose of intravenous phenobarbital in line with an approved protocol for the treatment of alcohol withdrawal, as well as adjunctive valproate therapy. The patient experienced resolution of withdrawal symptoms, had no complications, and ongoing abstinence at 60 days of follow-up. A single loading dose of phenobarbital in the inpatient setting is a viable alternative to prolonged outpatient tapers for the management of benzodiazepine withdrawal. Although this strategy requires further optimization, the prospect of a single-dose treatment for benzodiazepine withdrawal creates exciting opportunities for alternative management options and settings. This case describes the successful management of benzodiazepine withdrawal syndrome using a single loading dose of intravenous phenobarbital derived from an approved protocol for alcohol withdrawal syndrome.

Case 3: Refractory Seizures Continuing into Infancy in a Term Neonate with Definite History of Perinatal Asphyxia

A 7-day-old neonate presents to our NICU with multiple jerky movements of both upper and lower limbs and floppiness. He is the product of a third-degree consanguineous marriage and is born in a peripheral institution. He has a sister who is 6 years old and is healthy. ### Birth to 7 Days after Birth The neonate is born vaginally and requires bag and mask ventilation for 5 minutes. He is transferred to a level II NICU, where he stays for 5 days. He exhibits features of encephalopathy and also has a multifocal clonic seizure 2 hours after birth; he receives a single loading dose of phenobarbital. He is diagnosed as having hypoxic-ischemic encephalopathy (HIE) grade 2. Subsequently, his sensorium improves and he is discharged while breastfeeding exclusively. Since day 6, he has been having multiple episodes of multifocal clonic seizures and is brought to our NICU on day 7. ### Day 7 to Day 23 A strong suspicion of neurometabolic disorder arises in view of consanguinity and refractory seizures. He is nil per os. He requires full loading doses of antiepileptic drugs (AEDs) phenytoin and phenobarbital, after which his seizures stop. Testing for blood glucose, arterial lactate, pH, serum ammonia, urine ketones, and urine-reducing substances and tandem mass spectroscopy …

Phenobarbital pharmacokinetics in neonates and infants during extracorporeal membrane oxygenation.

The disposition of drugs is potentially changed due to extracorporeal membrane oxygenation (ECMO) in neonates and infants. The aim of the study was to evaluate the individual pharmacokinetics (PK) of phenobarbital and the effect of PK covariates in neonates and infants undergoing ECMO. Sixteen patients (7 neonates, 9 infants) treated with phenobarbital during ECMO (centrifugal-flow pump circuits) were enrolled in the PK study. Phenobarbital serum concentrations were measured using a fluorescence polarization immunoassay. Individual PK parameters - volume of distribution (Vd) and clearance (CL) were calculated in a one-compartmental pharmacokinetic model. The mean (SD) Vd and CL values in neonates were 0.46 (0.24) L/kg and 8.0 (4.5) mL/h/kg, respectively. Respective values in infants were 0.56 (0.23) L/kg and 8.5 (3.1) mL/h/kg. PK parameters in neonates and infants were not significantly different. We observed high inter-individual variability in PK parameters (coefficients of variation [CV] were 52% and 53% for CL and Vd, respectively). Doses were adjusted based on therapeutic drug monitoring (TDM) in 87.5% patients. Only 50% of the first measured phenobarbital serum concentrations in each patient were within the therapeutic range of 10-40 mg/L, in comparison with 88.6% concentration measured after TDM implementation. Linear regression models showed that both Vd and CL are significantly related with body weight (BW) and length. Median optimal phenobarbital loading dose (LD) and maintenance dose (MD), calculated from pharmacokinetic data, were 15 mg/kg and 4 mg/kg/day, respectively. Body weight was shown to be the main PK covariate of phenobarbital disposition. Subsequent dosing nomograms are provided for phenobarbital dosing during ECMO.

Clinical Pharmacology of Phenobarbital in Neonates: Effects, Metabolism and Pharmacokinetics.

Phenobarbital is an effective and safe anticonvulsant drug introduced in clinical use in 1904. Its mechanism of action is the synaptic inhibition through an action on GABAA. The loading dose of phenobarbital is 20 mg/kg intravenously and the maintenance dose is 3 to 4 mg/kg by mouth. The serum concentration of phenobarbital is up to 40 µg/ml. Nonresponders should receive additional doses of 5 to 10 mg/kg until seizures stop. Infants with refractory seizures may have a serum concentration of phenobarbital of 100 µg/ml. Phenobarbital is metabolized in the liver by CYP2C9 with minor metabolism by CYP2C19 and CYP2E1. A quarter of the dose of phenobarbital is excreted unchanged in the urine. In adults, the half-life of phenobarbital is 100 hours and in term and preterm infants is 103 and 141 hours, respectively. The half-life of phenobarbital decreases 4.6 hours per day and it is 67 hours in infants 4 week old.

Phenobarbital versus morphine in the management of neonatal abstinence syndrome, a randomized control trial.

BackgroundsEvaluating the efficacy of the loading and tapering dose of Phenobarbital versus oral Morphine in the management of NAS.MethodsThis randomized, open-label, controlled trial was conducted on 60 neonates born to illicit drugs dependent mothers at Vali-Asr and Akbar-Abadi hospitals, Tehran, Iran, who exhibited NAS requiring medical therapy. The neonates were randomized to receive either: Oral Morphine Sulfate or a loading dose of Phenobarbital followed by a tapering dose. The duration of treatment required for NAS resolution, the total hospital stay and the requirement for additional second line treatment were compared between the treatment groups.ResultsThe Mean ± Standard Deviation for the duration of treatment required for the resolution of NAS was 8.5 ± 5 days in the Morphine group and 8.5 ± 4 days in the Phenobarbital group (P = 0.9). The duration of total hospital stay was 12.6 ± 5.6 days in the Morphine group and 12.5 ± 5.3 days in the Phenobarbital group (P = 0.7). 3.3 % in the Morphine group versus 6.6 % in the Phenobarbital group required adjunctive treatment (P = 0.5).ConclusionsThere were no significant differences in the duration of treatment, duration of hospital stay, and the requirement for adjunctive treatment, between the neonates with NAS who received Morphine Sulfate and neonates who received a loading and tapering dose of Phenobarbital.Trial registrationThis study is registered at the Iranian Registry of Clinical Trials (www.irct.ir) which is a Primary Registry in the WHO Registry Network. (Registration Number = IRCT201406239568N8)

Can we safely administer the recommended dose of phenobarbital in very low birth weight infants?

We investigated whether the recommended phenobarbital loading dose of 15-20 mg/kg with maintenance of 3-4 mg/kg/day can safely be administered to very low birth weight preterm newborns with seizures. Twenty-four convulsive preterms of <1,500 g were enrolled in the study. Phenobarbital was administered intravenously with a loading dose of 15 mg/kg in approximately 10-15 min. After 24 h, the maintenance dose of 3 mg/kg/day was administered as a single injection. Blood samples were obtained 2, 24, 48, 72, and 96 h after the phenobarbital loading dose was administered, immediately before the next phenobarbital dose was injected. None of the cases had plasma phenobarbital concentrations above the therapeutic upper limit of 40 μg/mL on the 2nd hour; one case (4.7%), on the 24th; 11 cases (45.8%), on the 48th; 15 cases (62.5%), on the 72nd; and 17 cases (70.8%), on the 96th hour. A negative correlation was detected between the serum concentrations of phenobarbital and gestational age on the 72th (p, 0.036; r, -0.608) and 96th hour (p, 0.043; r, -0.769). We suggest that particular attention should be done while administering phenobarbital in preterms, as blood levels of phenobarbital are higher than the reference ranges that those are often reached with the recommended doses in these groups of babies.

Seizure-like Symptoms in a 2-day-old Term Female

A 2-day-old term female infant was noted to have lip smacking, eye twitching, and abnormal “jerking” left arm and leg movements. A loading dose of phenobarbital was given, but the episodes progressed to generalized clonic movements associated with apneas and desaturations requiring intermittent bag mask ventilation. A repeat dose of phenobarbital and a loading dose of phenytoin were given. A sepsis workup including complete blood cell count and blood culture was performed. A lumbar puncture was planned but was deferred because of the infant’s acutely deteriorating status. She was started on empiric antibiotics and acyclovir before ventilation for transfer to a tertiary referral hospital for further evaluation and management. Soon after arrival, a confluent erythematous rash presenting in a linear pattern was noted on the legs and lower trunk (Figs 1 and 2). Figure 1. Development of rash at 44 hours after birth. Figure 2. Leg rash presents in a linear pattern. ### Prenatal History: ### Birth History: Initial examination revealed a nondysmorphic, appropriate-for-gestational-age infant intubated and sedated on a ventilator. Anterior fontanelle noted to be full but soft. On neurological examination, infant was noted to have generalized hypertonia, increased deep tendon reflexes, and bilateral ankle clonus. Rash, as seen in figures, was nonvesicular in nature. Infant continued to have intermittent seizure activity associated with vital sign …

Index of Suspicion in the Nursery

Twins are born at 37-5/7 weeks gestation to a 41-year-old G4P2 woman who had unremarkable serology results. The delivery is via cesarean section because of a nonreassuring fetal heart rate. Twin B appears to be acrocyanotic and initially requires positive-pressure ventilation for 30 seconds before being able to maintain her oxygen saturation on her own. Apgar scores are 7 and 8 at 1 and 5 minutes, respectively. She also appears to be “jittery,” and her screening glucose concentration is 24 mg/dL (1.3 mmol/L). She consumes 20 mL of infant formula and a 10% dextrose (D10) infusion is begun at a rate of 60 mL/kg per day. Three hours after birth, a follow-up glucose evaluation measures 30 mg/dL (1.7 mmol/L), prompting administration of a 4-mL/kg bolus of D10 over 20 minutes and increase of the maintenance infusion rate to 100 mL/kg per day. Six hours after birth, glucose measures 80 mg/dL (4.4 mmol/L), and the infusion rate is decreased to 60 mL/kg per day. She is transferred to a hospital that has a neonatal intensive care unit (NICU) for close monitoring. On transfer, the oxygen saturation dips into the upper 80s/lower 90s, and nasal cannula administration of oxygen is initiated. Furthermore, during transfer (8 to 9 hours after birth), the blood glucose value is 44 mg/dL (2.4 mmol/l), so the D10 infusion rate is increased back to 100 mL/kg per day. On arrival at the second hospital, her oxygen saturation is about 85% and glucose is 50 mg/dL (2.8 mmol/L). In the NICU, she receives noninvasive respiratory support as well as 15% dextrose (D15) at a rate of 70 mL/kg per day. Twin A remains stable and continues to receive routine newborn care in the newborn nursery of the first hospital. Two days after birth, twin B continues to have glucose …

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.

Lorazepam Toxicity in a Premature Infant

To report a case of lorazepam toxicity in a premature infant and discuss the importance of altered pharmacodynamics and pharmacokinetics in the neonatal population. A 2025-g, 33-weeks' gestation infant was born with respiratory distress syndrome that required mechanical ventilation. Lorazepam was used to establish sedation and prevent asynchronous breathing while the infant was on the ventilator. Shortly after the first dose of lorazepam, the infant experienced a seizure and was subsequently given a loading dose of phenobarbital. Lorazepam therapy was continued for sedation. The patient was transferred to our tertiary care center on day 2 of life for evaluation of possible cardiac disease. Upon arrival, the infant was extremely hypotonic and unresponsive; therefore, all sedative medications were discontinued. Two days after admission, the infant continued to exhibit very little spontaneous activity and a lorazepam serum concentration was obtained (63 h after the last dose). Analysis revealed a toxic lorazepam serum concentration of 4453 nmol/L. The patient eventually was weaned to room air and was transported back to the referring hospital. Lorazepam is commonly prescribed in the pediatric population for sedative, anticonvulsant, anxiolytic, antiemetic, and amnestic activity. Few data exist regarding the safety of long-term lorazepam therapy in the neonatal subpopulation. There have been some reports of neurologic toxicity secondary to lorazepam in preterm infants. Its metabolism depends on glucuronidation, an enzymatic process that is very depressed in the premature infant. Accumulation of the drug in the neonate accompanied by clinical toxicity is highly likely. The inability to establish a clear pharmacokinetic-pharmacodynamic relationship, along with the increased incidence of reported adverse events of lorazepam in neonates, is concerning. Clinicians should be aware of the altered metabolism and elimination of lorazepam in the premature infant.

Safety of a Higher Loading Dose of Phenobarbital in the Term Newborn

The conventional loading dose of phenobarbital for newborn infants with hypoxic-ischemic seizures, 20 mg/kg, often fails to control convulsive activity. To determine the safety of a higher loading dose and to establish the pharmacokinetic parameters of a higher loading dose, ten severely asphyxiated term newborns were given 30 mg/kg of phenobarbital intravenously over 15 minutes. The mean serum concentration of phenobarbital two hours after loading was 30.0 +/- 3.2 micrograms/mL, the apparent volume of distribution was 0.97 +/- 0.18 L/kg, total clearance was 0.08 +/- 0.03 mL/min/kg, and mean serum half-life was 148 +/- 55 hours. The higher loading dose was not associated with any short-term adverse effects on cardiorespiratory function, even in spontaneously breathing infants.

420 THE COURSE OF HYPERBILIRUBINEMIA IN THE VERY LOW BIRTHWEIGHT INFANT TREATED WITH PHENOBARBITAL

We examined the effect of early phenobarbital therapy on the course of jaundice in 58 infants below 1500g. The study group of 28 infants (BW 1149+/-251g, GA 29.5+7-2.7wks), was treated with a phenobarbital loading dose of 20mg/kg/day at 4.2+/7-3.6 hrs of age, followed by a maintenance dose of 5mg/kg/day for one week. Thirty infants served as controls. Seventeen study and 20 control infants suffered from intraventricular hemorrhage. The results of the comparison showed that treated infants had lower peak serum bilirubin concentrations (7.9+/-1.7 vs 8.6+/7-2.2mg/dl), reached peak SBC levels earlier (92.5+/-50.7 vs 138.0+7-101.1 hrs) and spent less time on phototherapy (5.5+7-2.9 vs 7.5+/-3.S days). In the study group, although peak SBC was similar to that of no IVH infants, the IVH subgroup reached peak SBC later (112.8+/-53.0 vs 61.2+7-25.6 hrs) and spent more time on phototherapy (6.9+7-2.3 vs 3.2+/-2.4 days). Control IVH infants showed similar results with an age at peak of 150.0+7-100.3 vs 114.1+/-101.4 hrs and a duration of phototherapy of 8.8+7-3.7 vs 4.8+7-2.5 days when compared to control infants without IVH. In this group of infants P was effective in reducing the severity of hyperbilirubinemia as indicated by the decreased need for therapy. In addition, the presence of IVH contributed to the hyperbilirubinemia in both treated and control infants.

Induction effect of phenobarbital on carbamazepine-10,11-epoxide kinetics in the rhesus monkey.

A previous study showed that coadministration of phenobarbital (PB) and carbamazepine (CBZ) to the rhesus monkey resulted in an increase in the steady-state ratio of carbamazepine-10,11-epoxide (EPO) to CBZ. Several postulates were proposed suggesting in induction in the formation pathway of EPO. This study was undertaken to determine whether PB can also modify the elimination kinetics of EPO in monkey. Five rhesus monkeys received an intravenous bolus dose of EPO on day 1, day 5, and day 15. In addition, the animals received an acute loading dose (110 mg) of PB on day 5 followed by 10 daily maintenance doses (35 mg/day). Plasma samples were assayed for PB and EPO by GC/CI/MS. The mean (+/- SD) of plasma clearance (CL), volume of distribution (V), and half-life (t 1/2) during the control period for EPO were 5.57 +/- 2.15 liters/hr, 7.48 +/- 2.50 liters and 0.95 +/- 0.16 hr, respectively. An acute loading dose of PB had no significant effect on any of these pharmacokinetic parameters at p = 0.05. Subchronic administration of PB caused an increase in CL (8.23 +/- 2.03 liters/hr, p less than 0.05), a decrease in t 1/2 (0.67 +/- 0.09, p larger than 0.05 but less than 0.10), and no change in V. This study suggests that PB produces an increase in systemic and intrinsic hepatic clearance of EPO. Therefore, the reported increase in the EPO-CBZ steady-state ratio after PB administration could occur only if the formation clearance of EPO is increased to a greater extent than its elimination clearance.

Barbiturate and hypnosedative withdrawal by a multiple oral phenobarbital loading dose technique.

Although intravenous phenobarbital loading is effective in barbiturate withdrawal, controlled infusions of a drug are inconvenient. To develop a practical and more widely applicable method, oral loading doses of phenobarbital were given to 21 barbiturate addicts, whose estimated mean daily intake of barbiturates was 1 gm (range 0.5 to 4 gm). Twelve had a past or present history of barbiturate withdrawal seizures. Phenobarbital was given orally at a rate of 120 mg/hr until a predetermined clinical end point of phenobarbital effect was achieved. This end point was the presence of at least three of the following: nystagmus, drowsiness, ataxia, dysarthria, or emotional lability. The total phenobarbital loading dose (mean +/- SD) was 23.4 +/- 7.1 mg/kg, median phenobarbital concentration after loading was 35.9 mg/l (range 13.2 to 71.6 mg/l), and median half-life (t 1/2) of phenobarbital was 90 hr (range 38 to 240 hr). One patient with t 1/2 = 38 hr was given supplemental doses of phenobarbital. None developed seizures or other evidence of barbiturate withdrawal.

261 RAPID CONTROL OF NEONATAL NARCOTIC ABSTINENCE UTILIZING A PHENOBARBITAL LOADING DOSE METHOD

Phenobarbital has long been the drug of choice in controlling seizures and narcotic abstinence syndrome (NAS) in newborns. This report describes the relationship between dosage and serum concentration using a high oral loading dose of phenobarbital followed by maintenance dosing to provide therapeutic serum levels more rapidly than with previous methods. Twenty neonates born to narcotic dependent mothers were studied; all had NAS and were evaluated by an abstinence scoring system. When high abstinence scores were reported (>8), all received a loading dose of 16 mg/kg of phenobarbital orally to rapidly achieve an expected therapeutic serum level of 18 mcg/ml. Results showed a serum level of 16 mcg/ml ± 2.6 at 3 hours after the loading dose as determined by the EMIT technique. Serum levels (mcg/ml) at 12 and 24 hours after the loading dose were 18.9 ± 3 and 18.6 ± 3.4. If the infant responded with the expected therapeutic serum level, and if the abstinence score decreased to <8 (defined as control of symptoms), maintenance doses were begun. Daily maintenance dosing of 2 mg/kg/day allowed serum levels to decline at a desirable rate of 20% per day. These infants were more easily controlled and detoxified with the phenobarbital loading dose method than with previously accepted dosing regimens. Supported by NIDA Grant #DA01807 and Commonwealth of Pa. Contract #1674.