Intravenous Administration Of Phenytoin Research Articles

Phenytoin administration in the newborn and infant.

To evaluate the efficacy and safety of phenytoin (PHT) in the treatment of situation-related seizures and epilepsies in the newborn and infant; the clinical histories of 82 patients were retrospectively reviewed. Sixty patients received for status epilepticus (SE), intravenous PHT followed by long-term oral administration for 27 of them. The other 22 patients had oral treatment only. Intravenous administration made 55% of these patients seizure-free, whereas oral administration produced lasting seizure control in only 9.1%. During chronic oral treatment, it was most difficult to obtain adequate plasma concentrations in 69.1% of the patients, and 43.6% had side effects, most of which were related to very high plasma concentrations. In conclusion, in the first 2 years of life, intravenous administration of PHT is useful for SE, but oral treatment is poorly effective with difficulty to achieve appropriate and stable therapeutic plasma concentrations, and with frequent side effects.

Neuro-ophthalmological signs during rapid intravenous administration of phenytoin

We prospectively studied eye movement after rapid intravenous administration of phenytoin. Nineteen healthy young adults participated in a study of i.v. phenytoin pharmacokinetics. Subjects received a standard dose of 15 mg/kg at a rate of 25 mg/min, and were examined neuro-ophthalmologically before and at the end of the infusion. All patients had horizontal gaze-evoked nystagmus (HGN), and impairment of horizontal smooth pursuit (SP). Other signs were present in the following percentages: vertical gaze-evoked nystagmus ( 16 19 ,84%), and impairment of vertical SP ( 15 19 , 79%). Total and free phenytoin levels did not directly correlate with the degree of any of the neurological signs tested. By review of the past studies of nystagmus during phenytoin therapy, we propose that nystagmus is present consistently during toxicity with initial phenytoin therapy, but occurs less consistently during ongoing phenytoin use or chronic toxicity.

Comparison of Plasma Levels and Pharmacodynamics after Intraosseous and Intravenous Administration of Fosphenytoin and Phenytoin in Piglets

Comparison of Plasma Levels and Pharmacodynamics after Intraosseous and Intravenous Administration of Fosphenytoin and Phenytoin in Piglets

Pediatric use of intravenous and intramuscular phenytoin: lessons learned.

First developed in 1950, parenterally administered phenytoin offered substantial advantages over parenterally administered phenobarbital and paraldehyde, which were the treatments for status epilepticus until the 1960s. During the 1950s, clinical research established the pediatric dosage of parenteral phenytoin for the treatment of seizures, which was based on the adult dosage adjusted to each child's weight. Studies in the late 1970s and early 1980s established more appropriate dosing for neonates and children on a milligram-per-kilogram basis. Scientifically derived dosing guidelines have been available only for the past 12 years. Side effects associated with parenteral phenytoin, caused primarily by its high pH level and the propylene glycol content needed to increase its solubility, were frequently reported during the 1970s and 1980s, after 25 years of clinical use. Intravenous administration of phenytoin caused burning at the infusion site and was associated with severe local cutaneous reactions following infiltration into surrounding tissue, leading to a recommendation that intravenous phenytoin be avoided in young children and the elderly. The propylene glycol solvent was linked to seizures, arrhythmia, asystole, and hepatic and renal damage. When administered intramuscularly, phenytoin is poorly absorbed and can cause hemorrhagic necrosis of the soft tissues at the injection site. Many of these side effects can be avoided in children with the use of fosphenytoin.

Practice of Pentobarbital Therapy in Convulsive Status Epilepticus in Children with Epilepsy

Purpose: We studied the detailed practical procedures and management of the complications of pentobarbital (PTB) therapy for convulsive status epilepticus (C‐SE) in children with epilepsy. Methods: Eighty‐six episodes of C‐SE in 24 children with epilepsy that could not be abolished by intravenous administration (i.v.) of diazepam (DZP) and phenytoin (PHT) were given i.v. PTB. If C‐SE continued, lidocaine was given i.v. followed by drip infusion (d.i.v.). When C‐SE still continued, d.i.v. PTB was started under continuous EEG monitoring, and the dosages were increased until a burst suppression pattern (BSP) on the EEG, consisting of one burst per 10 s of suppression, or complete EEG suppression (CS) was obtained. The subjects included diagnoses of frontal lobe epilepsy (15 cases). other localization‐related epilepsies (two cases), Lennox‐Gastaut syndrome (four cases), and other symptomatic generalized epilepsies (three cases). Results: Seventy‐one episodes were terminated with i.v. PTB alone. C‐SE was completely abolished by one or more doses of PTB. 2.5–12.0 (mean, 4.6) mg/kg. during 61 episodes, and incompletely terminated by one or more doses of PTB, 1.5–10.0 (4.5) mg/kg, during 10 episodes. Mild respiratory depression developed during one episode with i.v. PTB, 5.4 mg/kg; however, this seemed to he caused by the previous administration of high doses of DZP, PHT, and phenobarbital (PB). Fifteen episodes required div. PTB. C‐SE was completely abolished by one d.i.v. course in 10 episodes and by two d.i.v. courses in two episodes; however, three episodes in three patients could not be stopped by two to four d.i.v. courses. The initial and maximal d.i.v. dosages were 0.5–2.0 (1.1) mg/kg/h and 0.5–4.0 (2.4) mg/kg/h in the successful cases, and 1.0–3.0 (1.8) mg/kg/h and 2.0–5.0 (3.4) mg/kg/h in the unsuccessful cases. Among 14 trials of d.i.v in 12 successful episodes, attempt of PTB discontinuation started based on BSP for 13–45 (30) h in nine trials, CS for 3348 (40) h in two trials, cessation of C‐SE for 9–17 (13) h in two trials, and hypotension in one trial. Among nine trials of PTB in three unsuccessful episodes, PTB could not be discontinued despite BSP for 17–82 (39) h in four trials and CS for 37–81 (56) h in three trials, and PTB was discontinued owing to poor general condition, administration of prednisolone, and surgical intervention. During PTB discontinuation, 10 of 15 episodes needed supportive therapy including i.v. PHT, DZP, or PTB, intramuscular PB. or rectal DZP or PB. Complications with d.i.v. PTB included respiratory depression requiring mechanical ventilation in 13 of 15 episodes, hypotension treated with vasopressors in 11 of 15, PTB precipitation and occlusion of the d.i.v. line in 10 of 15, markedly increased the C‐reactive protein (CRP) value in 13 of 15, decreased bowel movement or ileus in six of 15, and vasculitis in five of 15. Mechanical ventilation and vasopressors were not required until >1.5 mg/kg/h and >2.0 mg/ kg/h of PTB. PTB precipitation could be prevented by undiluted PTB or >10 times diluted PTB. Central venous line placement or highly diluted PTB solution could prevent vasculitis. Conclusions: PTB was effective and safe even by i.v., and d.i.v. was not mandatory in the treatment of C‐SE. Tapering of PTB in d.i.v. could be started after 30–40 h of BSP or CS. Mechanical ventilation and vasopressors were not needed until >1.5 mg/kg/h and >2.0 mg/kg/h of PTB. PTB precipitation could be prevented by using >I0 times diluted PTB or undiluted PTB. Caution must be paid to increased CRP, vasculitis, and ileus.

Recent advances in the pharmacotherapy of epilepsy

The therapeutic options for the treatment of epilepsy have expanded during the 1990s. Since 1993, four novel agents (felbamate, gabapentin, lamotrigine, and topiramate) have been approved by the US Food and Drug Administration, primarily for adjunctive treatment of partial seizures. In addition, a water-soluble pro-drug of phenytoin, fosphenytoin, and a sustained-release preparation of carbamazepine have been introduced. The novel anticonvulsants represent a potential improvement for patients whose seizures are incompletely controlled or who experience significant adverse effects with older anticonvulsants. Felbamate, lamotrigine, and topiramate appear to have a broad spectrum of action in seizure control, but felbamate use is limited by the potential for serious adverse effects. Gabapentin, lamotrigine, and topiramate are all well tolerated. Gabapentin has no known drug interactions, whereas lamotrigine and topiramate have limited interactions compared with older agents. The sustained-release preparation of carbamazepine may decrease the incidence of adverse effects and increase patient compliance. Fosphenytoin offers a safer method for intravenous administration of phenytoin and the added flexibility of intramuscular administration. Taken together, these recent advances in treatment may bring about improved efficacy and decreased adverse effects for many patients with epilepsy.

Association of intravenous phenytoin toxicity with demographic, clinical, and dosing parameters

Previous studies investigating intravenous phenytoin toxicity have been largely anecdotal, and have inferred an association with older patients, cardiovascular disease, and higher doses, concentrations, and infusion rates of phenytoin. This investigation sought to elucidate both the incidence and nature of acute intravenous phenytoin toxicity in emergency department patients, and to identify any demographic, clinical, or dosing associations with toxicity, by analyzing a retrospective case series over 3 years in a municipal teaching hospital. A consecutive series of 164 patients who received intravenous phenytoin loading in the emergency department following acute seizure presentation was identified. Demographic, clinical, and dosing data were collected, and the nature of toxicity was noted. Data were then analyzed statistically for potential associations with toxicity. Eight cases of hypotension and no apnea or arrhythmias were noted in the 164 patients (4.9% incidence). Analysis of demographic, clinical, and dosing data found statistically significant associations between hypotension and both a lower phenytoin dose administered (537 mg in hypotensive patients v 787 mg in normotensive patients, P = .00046) and the presence of abnormal neurological signs at initial presentation (20% incidence when abnormal signs present v 3.5% incidence when absent, P = .026). No other associations were found between toxicity and other variables. This sample size could detect differences ranging from 4% to 11% in complication rate (hypotension) for the various demographic, clinical, and dosing parameters with a statistical power of 80%. It was concluded that the incidence of hypotension from intravenous phenytoin administration in this study population was approximately 5%, and the incidence of apnea and cardiac arrhythmia in this series was 0%. No associations with age, comorbidities, or infusion rates were found, in contrast to other studies. Association of intravenous phenytoin toxicity with lower phenytoin dose is likely related to prompt cessation of the drug once signs of toxicity occur. The possible association of toxicity with abnormal initial neurological signs has not previously been reported and may possibly define a population at risk if validated by prospective research in additional populations.

Pentobarbital therapy for status epilepticus in children: Timing of tapering

Three children with refractory status epilepticus, unresponsive to intravenous administration of diazepam, phenytoin, and lidocaine, received pentobarbital therapy and were monitored by electroencephalography (EEG). They required mechanical ventilation and vasopressor therapy. Intravenous pentobarbital therapy was successful and without distinct sequelae in all 3 patients, and could be incrementally discontinued without breakthrough seizures after 12–65 hours of a burst-suppression or complete suppression pattern on EEG. Obtaining a suppression pattern was important for controlling status epilepticus in children as well as adults. We suggest that 12 hours after a burst-suppression pattern is obtained, tapering of pentobarbital should be attempted to avoid serious complications of extended pentobarbital anesthesia (e.g., respiratory depression, hypotension, pneumonia).

Complete atrioventricular block with ventricular asystole following infusion of intravenous phenytoin

A case of complete atrioventricular block with ventricular asystole in a patient receiving intravenous phenytoin is presented. Although the potential for hypotension is generally recognized with the intravenous administration of phenytoin, conduction abnormalities are rarely reported. The differential diagnosis of atrioventricular block and the effects of phenytoin on cardiac conduction are discussed.

Effect of phenytoin on acute lung injuries in unanesthetized sheep.

To determine if the intravenous administration of phenytoin attenuates or prevents acute experimental lung injury. Placebo-controlled, longitudinal animal investigative study. University research laboratory. Sixteen yearling female lambs weighing 30 +/- 3 kg. After administration of anesthesia, the animals were endotracheally intubated and mechanically ventilated. Using sterile techniques, four thoracotomies were performed. Through the left fourth intercostal space, cannulas for pressure measurements were inserted directly into the main pulmonary artery and left atrium. An ultrasound flow cuff for determination of cardiac output was placed around the main pulmonary artery. Through the left tenth intercostal space, the diaphragmatic and mediastinal parietal pleura were widely cauterized. Through the right tenth intercostal space, the caudal mediastinal lymph node was identified and divided at the caudal margin of the right pulmonary ligament, and a 1- to 2-cm portion of the node distal to the ligament was resected. The diaphragmatic and mediastinal parietal pleura were widely cauterized. Through the right sixth intercostal space, the efferent duct (or ducts) was identified, ligated at the site of entry into the thoracic duct, and cannulated. The lymph cannula was brought to the outside of the thorax through a separate stab wound. Unanesthetized sheep were studied 7 to 10 days after surgery. Hemodynamic, lung fluid balance, and arterial blood variables were measured in uninjured sheep and in sheep injured by intravenous infusions of Escherichia coli endotoxin (1 microgram/kg iv over 30 mins), air bubbles (0.056 to 0.074 mL/kg/min over 4 hrs), or oleic acid (0.06 mL/kg over 1 hr). The sheep were studied when untreated and after pretreatment with phenytoin. We found that the expected increase in protein-rich lung lymph flow with injuries, resulting from increased microvascular permeability in the lungs, was attenuated by phenytoin when the lungs were injured by endotoxin or air bubbles. In contrast, phenytoin had no effect on oleic acid-induced lung injury or on uninjured lungs. Phenytoin attenuates acute lung injuries in sheep that are thought to be caused by stimulation of host inflammatory responses (e.g., endotoxin and air bubbles), but has no effect on direct injuries to the lungs (e.g., oleic acid). A plausible mechanism for this finding is phenytoin inhibition of polymorphonuclear leukocyte function.

Cardiovascular side effects of emergency intravenous phenytoin administration

Cardiovascular side effects of emergency intravenous phenytoin administration

Phenytoin sodium solubility in three intravenous solutions

The solubility of phenytoin sodium injection of two manufacturer's was studied in three intravenous fluids, 0.9% sodium chloride, lactated Ringer's, and four manufacturers 5% dextrose injections. Phenytoin sodium for injection was added to 250 ml of an intravenous fluid to give calculated initial concentrations of 0.40, 0.98, 2.38, and 4.55 mg/ml. The pH of each solution was determined before and after the addition of phenytoin. Visual examination and nephelometric measurements for crystals were performed at various times between 5 and 1440 minutes after mixing. Phenytoin concentration was determined by spectrophotometry at these times; nephelometric measurements were done on unfiltered samples. The concentration of phenytoin declined rapidly in all dextrose solutions but at different rates for each brand. A greater stability was demonstrated when phenytoin was diluted in 0.9% sodium chloride and lactated Ringer's injections. Mean concentrations in excess of 95% of initial concentration were maintained for eight hours in those fluids. The two brands of phenytoin sodium injection did not differ consistently with respect to solubility. Crystals were observed in all dextrose solutions; nephelometric measurements indicated crystals were present in all solutions. The pH of all solutions increased sharply upon addition of phenytoin sodium injection. It is concluded that 0.9% sodium chloride and lactated Ringer's injections are suitable diluents for the intravenous administration of phenytoin. Factors other than pH and cosolvent concentration may affect phenytoin stability in dextrose solutions.

Correlation of serum phenytoin (diphenylhydantoin) with the administration of oral and intravenous phenytoin in dogs

The concentration of serum phenytoin was determined in normal dogs following the administration of phenytoin by either the intravenous or oral route. An intravenous dose of 11 and 33 mg/kg of body weight was given to six dogs and a further dose of 44 mg/kg was given to two dogs. Serial blood samples were taken following the three doses for determination of pharmacokinetic parameters. The mean half‐life was 3.35, 3.84 and 4.57 h as the dose was increased. Signs of toxicity occurred immediately following the infusion of phenytoin (emesis, ataxia and seizures). In the first oral studies, serial blood samples were taken for 2 consecutive days following a dose of 11 and 88 mg/kg, t.i.d. The time—concentration profiles of phenytoin varied significantly from one day to the next in the same dog. In the second oral study, blood samples were taken at 3 and 7 h following a dose of 11, 22, 44, 66 and 88 mg/kg, t.i.d. There was a poor correlation between the size of the oral dose and the concentration of serum phenytoin. Due to the short half‐life and poor absorption of phenytoin in dogs, it was concluded that the oral administration of phenytoin in dogs produces sub‐therapeutic and erratic serum concentrations of phenytoin which makes its efficacy as an anti‐convulsant questionable.

Intravenous administration of phenytoin

Intravenous administration of phenytoin

Intravenous Administration of Phenytoin

Intravenous Administration of Phenytoin