Pearls & Oy-sters: Soft-tissue necrosis as a result of intravenous leakage of phenytoin
C. A. Twardowschy, MD,
L. De Paola, MD,
F.M.B. Germiniani, MD,
L. C. Werneck, MD and
C. Silvado, MD
From the Epilepsy Surgery Program, Hospital de Clínicas, Universidade Federal do Paraná, Brazil.
Address correspondence and reprint requests to Dr. Carlos Silvado, Hospital de Clinicas UFPR, Rua General Carneiro, 181 3° andar, Curitiba, Paraná, Brazil CEP 80.060-900 silvado{at}hc.ufpr.br
Phenytoin leakage can cause potentially serious side effectsrangingfrom mild edema to soft-tissue necrosis.
To avoid such events,one should consider using:
a dedicated IV catheter insertedin a large peripheral veintoinfuse phenytoin;
administrationrate 50 mg/min;
periodicflushing with saline after each bolus;
continuousmonitoringfor signs of extravasation, hypotension,and bradycardia.
Theease of administration, rapid onset of action, minimal morbidity,andIV solution compatibility are potential advantages of someofthe second-line anticonvulsant agents, like valproate.
In the past 70 years, phenytoin (PHT) has been used in the managementof seizures and remains, despite the advent of newer antiepilepticdrugs,1 one of the preferred long-acting antiepileptic drugsin the treatment of convulsive status epilepticus.2 Injury dueto PHT leakage may result in damage ranging from simple, mildphlebitis to severe lesions such as soft tissue necrosis.3,4Up to 20% of IV administration of all drugs results in recognizedepisodes of extravasation.5 Nevertheless, few studies addressthe adverse events associated with the IV use of PHT.2,6 Factorsbelieved to affect the extent of injury include the chemicalproperties of the drug, health status of the patient, and postextravasationcare.3 We report the case of a 52-year-old woman who developedskin necrosis following IV administration of PHT as treatmentof generalized convulsive status epilepticus (GCSE) and suggestsome recommendations.
A 52-year-old woman was admitted for presurgical evaluationof refractory epilepsy. During video-EEG monitoring, the patientdeveloped GCSE lasting 18 minutes, not responsive to diazepam10 mg IV. Undiluted 1,250 mg of PHT (20 mg/kg) was infused inthe same peripheral venous line over 9 minutes, during whichthere were no symptoms or physical signs of extravasation. Approximately6 minutes after onset of PHT infusion, the seizure and electrographicstatus epilepticus ceased. Within 2 hours, the patient was alertand started to complain of a burning sensation in the area ofinfusion. An erythematous lesion could be seen in that region.Four hours later, a new examination disclosed a large area ofswelling and hyperemia with a central area of skin necrosiswith a typical black coloration (figure, A). Radial and ulnararterial pulses were preserved. She had mild pain at the lesionsite. Tissue and blood samples were collected for culture, whichturned out to be negative. Other laboratory examination resultswere also normal. A plastic surgery consultation suggested localdebridement as the appropriate treatment (figure, B).
(A) Four hours after phenytoin infusion: erythema, edema, and central soft tissue necrosis. (B) Two weeks after infusion: signs of wound healing with adequate scar tissue.
Along with phenobarbital, PHT remains one of the most widelyused antiepileptic drugs in the acute treatment of GCSE.1,2The introduction of oral PHT in 1938 and its subsequent parenteralformulation represented a significant advance in anticonvulsanttherapy.
PHT is a highly alkaline (pH 12), poorly water soluble compound.Because of the risk of systemic adverse effects, like hypotensionand cardiac arrhythmias, administration is usually carried outat no more than 50 mg/min. Mixing PHT with 5% dextrose may resultin lack of solubility and precipitation, but it can be dissolvedin no more than 20 mg/mL in normal saline without such problems.2The parenteral formulation of IV PHT produces pain at the injectionsite and is irritating to soft tissue, sometimes resulting inphlebitis. In order to reduce this complication, injection ofsterile saline is recommended during and after the administrationof IV PHT.2
Local complications like edema, phlebitis, tissue necrosis,and the "purple glove" syndrome7 may occur. In a prospectivestudy that assessed the adverse side effects following the useof IV PHT,4 6 patients (27%) experienced one or more side effects,including extravasation of the drug, hypotension, and cardiacarrhythmia.
PHT can be associated with potentially serious side effectsranging from mild edema to soft-tissue necrosis.8 Therefore,one should follow patients closely after IV PHT infusion andconsider the following recommendations: 1) use a dedicated IVcatheter in a large peripheral vein to infuse phenytoin; 2)administration must be carried out at no more than 50 mg/min(in children and elderly no more than 25 mg/min); 3) periodicallyflush the IV access with saline bolus during the PHT infusion;4) systematically monitor for signs of extravasation, hypotension,and bradycardia; 5) closely follow neurologic and circulatorystatus of the patient.
Fosphenytoin is an alternative to PHT, as it can be administeredmore quickly and safely.9 Likewise, other newer antiepilepticdrugs are emerging as potential options for treatment of GCSE.1IV valproate has several potential advantages: it can be easilyadministered at faster infusion rates, is effective in all agegroups, has a rapid onset of action, has proven broad-spectrumefficacy, and has minimal side effects, all of which may warrantits inclusion in status epilepticus treatment protocols. Levetiracetam,despite somewhat mixed results in animal studies, has been reportedto be successful in case reports in human GCSE.10 These preliminaryreports suggest a possible role of levetiracetam in the initialmanagement of status epilepticus, especially due to its easeof use, administration, and limited side effects. Recently,IV lacosamide was reported as a successful treatment optionfor nonconvulsive status epilepticus.11 Prospective randomizedtrials with the new anticonvulsants are encouraged.
Dr. Twardowschy reports no disclosures. Dr. De Paola servesas Editor of the Journal of Epilepsy and Clinical Neurophysiology.Dr. Germiniani, Dr. Werneck, and Dr. Silvado report no disclosures.
Disclosure: Author disclosures are provided at the end of thearticle.
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