Intravenous Administration Of Phenytoin Research Articles

A Rare Complication of Intravenous Phenytoin Induced Purple Glove Syndrome

Purple Glove Syndrome is a relatively uncommon complication of intravenous phenytoin administration withclinical manifestations of pain, edema, and purple-blue discoloration at the injection site. Here we report a caseof Purple Glove syndrome induced by intravenous administration of phenytoin. The case report describes about a75-year-old male, who presented to the Emergency Department with chief complaints of generalized tonic - clonicseizures for which he was managed with Inj. Phenytoin. Later patient sensorium improved and 4 hours later thepatient had pain and swelling over the left hand and wrist distal to the IV cannula site followed by reddish-purplediscoloration over the edematous site. Left upper limb Doppler was done & it showed left-hand cellulitis with noevidence of thrombus. Then the patient was reassured and treated with removal of IV cannula, left-hand elevation,warmth application, analgesics and change of antiepileptics. Such medications like phenytoin should be handledcarefully to avoid difficulties in the future. Early detection, rapid monitoring, and management are essential.

Purple Glove Syndrome- A Catastrophic Complication of Phenytoin Injection

Purple Glove Syndrome (PGS) is a rare complication of intravenous phenytoin administration which is illustrated by delayed soft tissue injury of the skin conterminous to the point or distal to the site of intravenous phenytoin infusion. The clinical features of PGS include pain, oedema, and bluish discolouration over the extremity. The present case report describes about a 60-year-old male, who presented to the Emergency Department with the chief complaints of generalised tonic clonic seizures, lasting for 10 mins, for which he was managed with inj. phenytoin sodium. The computed tomography scan of brain revealed right-sided subdural haematoma. After 24 hours of hospital stay, the patient started complaining of severe pain in the arm and forearm. There was purple-bluish discolouration around the intravenous site, peripheral oedema and pain. The various risk factors linked to PGS, include old age and large and multiple doses of phenytoin.

Efficacy of intravenous levetiracetam versus phenytoin in convulsive status epilepticus and acute repetitive seizures in children.

Phenytoin is one of the most used antiepileptic drugs (AEDs), but it has serious potential side effects and drug interactions. Although studies have shown levetiracetam to have a much lower side-effect profile, its efficacy when compared with phenytoin is debatable. In our study, we aimed to determine the factors that cause seizure recurrence and to compare the efficacy of levetiracetam and phenytoin in the treatment of convulsive status epilepticus (CSE) and acute repetitive seizures (ARS). In this study, 185 patients diagnosed with CSE or ARS and aged between 1month and 18years who received intravenous levetiracetam or phenytoin as a second-line AED were retrospectively evaluated. A total of 185 patients were included in the study, 85 (45.9%) girls and 100 (54.1%) boys.While 54.1% (n = 100) of the patients were given phenytoin, levetiracetam was administered to 45.9% (n = 85) of them. The rates of cessation of seizure and prevention of seizure recurrence for 24h were 84% for phenytoin and 78.8% for levetiracetam, without a significant difference (p > 0.05). Having active seizures on admission to the emergency department and an age of < 36months were significantly related to seizure recurrence (p < 0.01). Our results support that the intravenous administration of levetiracetam as the second-line treatment for CSE and ARS in children is as effective as the intravenous administration of phenytoin.

Rapid infusion of excessive phenytoin: A newborn autopsy case.

The patient was a two-day-old female infant. The patient's mother was a primigravid in her 20s who developed premature abruption of the normal placenta on the first day of the 33rd week of gestation. The infant was born by emergency cesarean section with severe neonatal asphyxia with a birth weight of 1928g. Spontaneous circulation was returned 11min after birth. The infant was treated under mechanical ventilation in the neonatal intensive care unit, and phenobarbital was administered for repeated seizures. On day 2, spontaneous respiration was observed; however, the patient developed seizures repeatedly. The dose of phenobarbital reached the maximum and was switched to midazolam. In the early morning of day 3, while midazolam was administered up to the maximum dose, the infant developed status epilepticus, and the anticonvulsant drug was changed to phenytoin. Due to a calculation error, the intravenous administration of phenytoin was started at 400mg/30min, which is 10-fold of the normal dose. Six minutes later, after 80mg was administered, the administration was stopped due to a drop in blood pressure; however, the infant died of cardiac arrest. An autopsy, which was performed approximately 25h after death, revealed the blood phenytoin concentration in the heart was 63.85μg/mL. The cause of death was determined to be acute phenytoin toxicity. This is the first fatal case reported of the blood concentration of phenytoin caused by rapid intravenous administration.

1059: A Survey of Intravenous Phenytoin Administration and Monitoring Practices in Adult Patients

1059: A Survey of Intravenous Phenytoin Administration and Monitoring Practices in Adult Patients

A Junctional Rhythm Caused by Administration of Intravenous Phenytoin

Introduction: We present the case of a patient with symptomatic junctional rhythm caused by administration of intravenous phenytoin. However, bradycardia and hypotension are more commonly associated with rapid infusion of intravenous phenytoin. In our patient, the rate of intravenous phenytoin administration was <50 mg/min.Case Report: A 79-year-old woman presented to the emergency department with altered mental status for 2 h and focal seizure. After phenytoin was intravenously infused over 45 min, junctional rhythm, unresponsiveness, and hypotension developed. Atropine, dopamine, and transcutaneous pacing were initiated. After the intervention, a normal sinus rhythm with a normal heart rate was maintained. The patient was admitted to the neurological intensive care unit. Conclusion: Emergency physicians should monitor patients for possible arrhythmic effects of intravenous phenytoin therapy. In addition to geriatric patients and patients with a history of cardiac disease, there may be an increased risk of cardiotoxicity for phenytoin even at the recommended dose and infusion rate in patients with end-stage renal disease

An anaesthesiologist's encounter with purple glove syndrome.

Purple glove syndrome (PGS) is a devastating complication of intravenous (IV) phenytoin administration. Anaesthetic management during the amputation of the limb for such patients is very challenging due to limited clinical experience. A 65-year-old woman developed PGS of left upper extremity after IV administration of phenytoin following generalised tonic-clonic seizures. The condition progressed rapidly leading to gangrene of left hand extending to the mid arm. Amputation was carried out under general anaesthesia with a supraglottic airway device. We discuss the prevention and alternate managements in PGS, which is a rare clinical entity with limited data in the literature.

Phenytoin Removal by Continuous Venovenous Hemofiltration

To describe 2 cases of clinically significant phenytoin removal during continuous venovenous hemofiltration (CVVH) and review the relevant literature regarding phenytoin removal by renal replacement modalities. A 64-year-old female with chronic kidney disease and cirrhosis was admitted to the intensive care unit (ICU) with a traumatic subdural hematoma and seizures. The patient received a loading dose of intravenous phenytoin 1000 mg, followed by maintenance intravenous administration of phenytoin 100 mg and levetiracetam 250 mg every 12 hours. CVVH was initiated for acidosis. A 63-year-old male was admitted to the ICU after cardiac surgery complicated by hypotension. CVVH was initiated for fluid overload, and phenytoin was initiated 3 days later for seizures. A loading dose of intravenous phenytoin 2700 mg was administered, followed by maintenance dosing of intravenous phenytoin 150 mg every 8 hours. Concentrations of unbound phenytoin in serum and CVVH effluent samples were measured during concomitant treatment in each patient. In both patients, serum and effluent concentrations of unbound phenytoin fell steadily while they were on CVVH. Clearance of phenytoin by CVVH was calculated, as was the daily removal of phenytoin, as a percentage of total daily phenytoin dosage during each sampling period. Phenytoin clearance by CVVH ranged from 11 to 13 mL/min in these patients. The clearance of phenytoin with CVVH in these 2 patients was much higher than the renal clearance of phenytoin reported in healthy volunteers with normal renal function. Previous case reports have demonstrated that only small, clinically insignificant amounts of phenytoin are removed by hemodialysis, and the only published report of phenytoin removal by continuous renal replacement therapy used hemofiltration rates much lower than those used in the 2 cases described here. These cases demonstrate that a substantial amount-approximately 30%-of total daily phenytoin dose may be removed by CVVH, and patients may require higher than expected empiric doses. Phenytoin concentrations should be closely monitored in critically ill patients receiving CVVH.

Compartment syndrome as a spectrum of purple glove syndrome following intravenous phenytoin administration in a young male: A case report and review of literature

Compartment syndrome is a rare complication of spectrum of purple glove syndrome, seen as a side effect of intravenous phenytoin. This involves rapid discolouration of the involved limb along with edema and sometimes blistering of the skin also. Treatment is usually conservative and rarely requires surgery. We present a case of compartment syndrome following intravenous phenytoin administration and review of literature related to the case.

Purple Glove Syndrome after Intravenous Phenytoin Administration Presenting in the Emergency Department

Purple Glove Syndrome after Intravenous Phenytoin Administration Presenting in the Emergency Department

Cough and Bronchospasm After Rapid Intravenous Administration of Phenytoin

Department of Neuroanaesthesiology All India Institute of Medical Sciences New Delhi, India The authors have no funding or conflicts of interest to disclose.

Low-concentration, continuous brachial plexus block in the management of Purple Glove Syndrome: a case report.

IntroductionPurple Glove Syndrome is a devastating complication of intravenous phenytoin administration. Adequate analgesia and preservation of limb movement for physiotherapy are the two essential components of management.Case presentationA 26-year-old Tamil woman from India developed Purple Glove Syndrome after intravenous administration of phenytoin. She was managed conservatively by limb elevation, physiotherapy and oral antibiotics. A 20G intravenous cannula was inserted into the sheath of her brachial plexus and a continuous infusion of bupivacaine at a low concentration (0.1%) with fentanyl (2 μg/ml) at a rate of 1 to 2 ml/hr was given. She had adequate analgesia with preserved motor function which helped in physiotherapy and functional recovery of the hand in a month.ConclusionA continuous blockade of the brachial plexus with a low concentration of bupivacaine and fentanyl helps to alleviate the vasospasm and the pain while preserving the motor function for the patient to perform active movements of the finger and hand.

Purple Glove Syndrom nach peripherer venöser Phenytoin Gabe – Ein Fallbericht

The purple glove syndrome (PGS) is a soft tissue injury after peripheral intravenous phenytoin administration or oral overdosage. The incidence of PGS is described with 0-6%. Typical symptoms are purple discoloration, oedema, pain, and a decrease of range of motion. In severe cases PGS may lead to abscess, skin loss and compartment syndrome. The established treatment of PGS is immediate interruption of phenytoin injections, splinting, elevation, and close observation. In cases of severe complications (e. g., compartment syndrome), surgical intervention is necessary. The case of a 40-year-old female patient is reported who was transferred to our department 4 days after intravenous phenytoin administration and who underwent successful surgical revision.

Cyclic hyperammoniemic encephalopathy and epileptiform triphasic waves: problems in differential diagnosis with nonconvulsive status epilepticus

Dear Editor, We would like to make three points about the case of cycling hyperammoniemic encephalopathy in an old women with a past history of uterosigmidostomy discussed by Tremolizzo et al. [1]. The first point concerns diagnosis of nonconvulsive status epilepticus (NCSE). De novo NCSE is not infrequent in elderly patients but as emphasized by Walker et al. [2] the diagnosis is often made with significant delay because the clinical picture of NCSE is difficult to differentiate from that of a metabolic encephalopathy unless an EEG is obtained. NCSE is under-recognized in clinical practice and a high level of suspicion is essential. There is the low awareness among physicians of the diagnostic utility of emergent EEG [3]. The second point is that a large spectrum of EEG ictal abnormalities may be observed in NCSE, including triphasic wave (TWs) with epileptiform characteristics. In particular, Kaplan (1999) [4] stressed that ‘‘when TWs appear with a frequency exceeding 1/s the distinction between encephalopathy and NCSE is difficult’’ and reported an EEG tracing showing flurries of triphasic waves (TWs) in a waxing and waning pattern in a patient with hyperammonemia. These EEG abnormalities are very similar to EEG pattern reported by Tremolizzo et al. Differential diagnosis between TWs of metabolic encephalopathy versus spike wave stupor was previously discussed [4]. In these cases it is mandatory to search a risk factor of mental status impairment (toxic-metabolic encephalopathy, as electrolytic imbalance, drugs toxicity, renal or liver failure, etc.) [5]. Finally, the immediate administration of benzodiazepines (lorazepam, diazepam) is the unequivocal first step for the treatment of NCSE. Bolus administration of intravenous valproic acid or phenytoin may be tried beyond benzodiazepines, but phenytoin should be used only in focal NCSE as it may cause aggravation of absence status [5].

Pharmacokinetics of phenytoin and its metabolite, 4′‐HPPH, after intravenous and oral administration of phenytoin to diabetic rats induced by alloxan or streptozotocin

It has been reported that diabetic patients have an increased risk of developing epileptic convulsions compared with the non-diabetic population, and phenytoin has widely been used for neuralgia in diabetic neuropathy. It has also been reported that in both diabetic rats induced by alloxan (DMIA rats) and by streptozotocin (DMIS rats), the protein expression and mRNA level of 2C11 decreased, but in DMIS rats, the protein expression of CYP2C6 increased. Thus, the pharmacokinetics of phenytoin and 4'-HPPH were investigated after intravenous or oral administration of phenytoin at a dose of 25 mg/kg to DMIA and DMIS rats. After intravenous or oral administration of phenytoin, the AUC (or AUC(0-12 h)) values of both phenytoin and 4'-HPPH were comparable (not significantly different) between each diabetic and the respective control rats. Although the exact reason is not clear, this could have been due to opposite protein expression (and/or mRNA levels) of CYP2C6 and 2C11 in diabetic rats.

Purple glove syndrome following intravenous phenytoin administration

Purple glove syndrome (PGS) is a rare complication of intravenous phenytoin use that typically presents with pain, edema, and discoloration at the injection site that spreads to the distal limb. Several risk factors have been associated with the development of PGS; however, the etiology remains unknown. We present a case of PGS and briefly review the current understanding of this syndrome.

Fosphenytoin for the treatment of status epilepticus: an evidence-based assessment of its clinical and economic outcomes

Status epilepticus (SE) is a life-threatening condition requiring prompt treatment in the emergency department to control seizures and limit potential neurologic damage. Fosphenytoin is a water-soluble prodrug of phenytoin (an established treatment option for SE) that has been developed to overcome the often severe venous adverse events that can occur following the intravenous administration of phenytoin. The objective of this article is to review the evidence for the use of fosphenytoin in the treatment of SE. Fosphenytoin can be infused more rapidly than phenytoin and there is evidence that therapeutic drug levels are achieved at least at a similar rate. Although few studies have been conducted in SE patients, there is evidence that fosphenytoin is at least as effective as phenytoin in terms of response and control of SE. There is also moderate evidence that there are fewer vascular adverse events following intravenous fosphenytoin compared with phenytoin administration when both drugs are infused at the recommended dosage and rate. Evidence from pharmacoeconomic studies indicates that a reduction in the incidence of adverse events and their subsequent management are critical factors for cost-effectiveness with fosphenytoin. In conclusion, fosphenytoin is a valuable treatment option for the rapid treatment of SE; the risk of venous adverse events is lower than with phenytoin when administered at the recommended rate.

Síndrome opercular anterior como manifestación de estado epiléptico no convulsivo

Foix-Chavany-Marie syndrome, or bilateral anterior opercular syndrome, is characterised by facio-pharyngo-glosso-masticatory diplegia with 'automatic-voluntary dissociation', which consists in the abolition of voluntary movements while involuntary movements and reflexes are preserved. It is produced by bilateral involvement of the anterior or frontal opercular region. In adults it is related to ischemic lesions. In childhood it presents congenitally in perisylvian dysplasias and as an acquired disorder in encephalitis or can be episodic in symptomatic or idiopathic epilepsies such as benign rolandic epilepsy. A 13-year-old patient who presented, over five straight days, four episodes of facial dysplegia, anarthria, dysphagia, drooling, paralysis of the upper limbs, while involuntary facial expression was normal and the corneal, cough and gag reflexes were preserved. The first three come to an end spontaneously at 2, 4 and 20 hours, respectively; the fourth episode concluded an hour and a half after onset, following administration of intravenous phenytoin for 5 minutes. Computerised axial tomography and magnetic resonance images of the brain, as well as the interictal electroencephalograms (EEG), were normal. Administration of oxcarbazepine was started but at 8 months was stopped after a normal EEG during nocturnal sleep was obtained. After 15 months, the patient has not presented any more episodes. The paroxysmal character of the disorder together with normal interictal periods, the normality of the neuroimages, and the speedy recovery achieved after the administration of phenytoin support the notion of an epileptic origin. We believe that we are dealing with a bilateral anterior opercular syndrome due to a non-convulsive epileptic state, compatible with the presentation of benign rolandic epilepsy.

Effects of cysteine on the pharmacokinetics of intravenous phenytoin in rats with protein–calorie malnutrition

The effects of cysteine on the pharmacokinetics of phenytoin and one of its metabolites, 5-( p-hydroxyphenyl)-5-phenylhydantoin ( pHPPH) were investigated after intravenous administration of phenytoin, 25 mg/kg, to control rats (4-week fed on 23% casein diet) and rats with PCM (protein–calorie malnutrition, 4-week fed on 5% casein diet) and PCMC (PCM with oral cysteine supplementation, 250 mg/kg, twice daily starting from the fourth week). In rats with PCM and PCMC, the phenytoin hydroxylation (to form pHPPH) activities were significantly smaller (164, 103 and 95.3 pmol/min per mg protein for the control rats, and rats with PCM and PCMC, respectively) than that in control rats. In rats with PCMC, the intrinsic clearance of phenytoin, CL int was significantly slower than those in control rats and rats with PCM (0.175, 0.131 and 0.044 ml/min). The above data suggested that the formation of pHPPH could be reduced in rats with PCM and PCMC. This was supported by significantly smaller 24-h urinary excretion of pHPPH (54.7, 35.6 and 32.5% of intravenous dose of phenytoin) in rats with PCM and PCMC than that in control rats. In rats with PCM, the maximum velocity (0.344, 0.203 and 0.196 μg/min), apparent volume of distribution in central compartment (44.4, 65.4 and 72.2 ml/kg) of phenytoin, and total area under the plasma concentration–time curve from time zero to time infinity (609, 714 and 1210 μg min/ml), renal clearance (20.5, 13.4 and 4.67 ml/min per kg) and 24-h urinary excretion (54.7, 35.6 and 32.5% of intravenous dose of phenytoin) of pHPPH were not returned to control levels by cysteine supplementation (rats with PCMC). This could be mainly due to the fact that the phenytoin hydroxylation activity in rats with PCMC was not returned to control level.

Comparison of plasma levels and pharmacodynamics after intraosseous and intravenous administration of fosphenytoin and phenytoin in piglets.

OBJECTIVE: To compare plasma drug levels and pharmacodynamics of fosphenytoin or phenytoin when given intraosseously or intravenously in doses relevant to children. DESIGN: Prospective controlled randomized study. SETTING: University hospital animal laboratory. SUBJECTS: A total of 40 mixed-breed piglets (age, 4-6 months; weight, 20-40 kg). INTERVENTIONS: The animals were anesthetized, after which they underwent intubation, instrumentation, and mechanical ventilation. A central venous catheter and an arterial catheter were placed for monitoring and blood sampling. A peripheral intravenous catheter with a 15-gauge intraosseous needle was inserted for drug infusion. A total of 40 animals (ten per group) were randomly assigned to receive intravenous or intraosseous phenytoin or fosphenytoin infusions. Phenytoin (20 mg/kg) was infused over 20 mins, and fosphenytoin (20 mg phenytoin equivalent kg) was infused over 7 mins. All infusions were followed by the administration of a 5-mL normal saline flush. MEASUREMENTS AND MAIN RESULTS: Blood samples (3 mL) were drawn for use in determining drug levels before infusions (baseline) and 0, 5, 10, 15, 20, 30, 40, 50, 60, and 75 mins after the infusion had been completed. Repeated measures of analysis of variance were used to evaluate statistical significance (p <.05). Phenytoin levels were undetected at baseline. Free (10 to 20 &mgr;g/mL) and total (80 to 110 &mgr;g/mL) phenytoin levels were well above the therapeutic range (free, 1 to 2 &mgr;g/mL; total, 10 to 20 &mgr;g/mL) after infusion in the animals that received fosphenytoin. Significant differences in values were seen in free phenytoin levels at 0 to 10 mins (p <.05) and in total phenytoin levels at 0 to 20 mins (p <.05) between intraosseous phenytoin or fosphenytoin administration. Similar differences were also seen when piglets that received intravenous phenytoin were compared with those that received intravenous fosphenytoin. From 20 to 75 mins, all groups had free and total levels within the therapeutic range. There were no significant differences among heart rate and blood pressure in the groups. CONCLUSION: There is no need to adjust standard drug doses of phenytoin when given intraosseously. The initial high levels of phenytoin in the fosphenytoin groups are of concern because neurologic toxic effects may occur in humans at those levels. Slower infusion rates of fosphenytoin may be needed to avoid toxic levels.