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1 Dicle University, Faculty of Medicine, Department of Neurology, Diyarbakır, Turkey  2 Dicle University, Faculty of Medicine, Department of Anesthesiology and Reanimaon, Diyarbakır, Turkey  

3 Dicle University, Faculty of Medicine, Department of Neurosurgery, Diyarbakır, Turkey 

Correspondence: Eşref Akıl,Dicle University, Faculty of Medicine, Department of Neurology, Diyarbakır, Turkey Email: esrefakil@gmail.com

Received: 02.10.2013, Accepted: 04.12.2013

Copyright © JCEI / Journal of Clinical and Experimental Invesgaons 2014, All rights reserved

JCEI / 2014; 5 (1): 108-111

Journal of Clinical and Experimental Invesgaons doi: 10.5799/ahinjs.01.2014.01.0371

CASE REPORT / OLGU SUNUMU

Status epilepcus induced by intrathecal bupivacaine use: A case report

İntratekal bupivakain kullanımına bağlı status epilepkus: Olgu sunumu

Eşref Akıl1, Sefer Varol1, Abdulmenaf Güzel2, Cüneyt Göçmez3

ÖZET

Lokal anestezkler anestezk ve postoperatf analjezk ola-rak sıkça kullanılmaktadırlar. Bupvakan en sık kullanı-lan amd grubu lokal anestezk maddelerden brdr. Amdgrubu lokal anestezklern santral snr sstem(SSS)’dedepresyon, nöbet ve blnç değşklğne neden olurkenkardyovaskuler sstem (KVS)’de artmlere yol açmakta-

dır. Spnal lokal anestezklern nörolojk komplkasyonla-rın nedenler lacın yüksek dozda verlmes, hızla sstemkdolaşıma geçmes, yanlışlıkla İV verlmes ya da lacınsefale doğru yayılmasıdır. Bzm olgumuzda ntratekal bu-pvakan kullanıldı. İntratekal bupvakan kullanımına bağlı jeneralze myoklonk nöbet bldrlmştr. Ancak araştırma-larımıza göre ntratekal bupvakan kullanıma bağlı Jene-ralze tonk klonk (JTK) tarzda status epleptkus olgusubldrlmemştr. Olgumuz ntratekal bupvakan kullanımsonrası gelşen JTK tarzda status epleptkus vakası ol-ması neden le sunuldu.

Anahtar kelimeler: Lokal anestezkler, status epleptkus,

bupvakan

ABSTRACT

Local anesthetics are commonly used as analgesics andanesthetics. Local anesthetics from the amide group maylead to symptoms of the central nervous system (CNS)such as depression, seizures or altered mental state,while they may lead to arrhythmia in the cardiovascularsystem (CVS). The causes of the neurologic complica-

tions observed with spinal local anesthetics are the ad-ministration of high doses, rapid entry into the systemiccirculation, erroneous administration through the IV route,or the diffusion of the drug towards the cephalic region.Bupivacaine is among the most commonly used localanesthetics from the amide group. However rare, neuro-logical injury after administered bupivacaine can be dis-tressing to patients and their families. In our patient, wehave administered bupivacaine through the intrathecalroute. Thus, we would like to present a case where statusepilepticus in the form of generalised tonic-clonic seizures(GTC) has developed subsequent to the intrathecal ad-ministration of bupivacaine. J Clin Exp Invest 2014; 5 (1):108-111

Key words: Local anesthetics, status epilepticus, bupi-vacaine

INTRODUCTION

Local anesthetics are commonly used as analgesicsand anesthetics. Bupivacaine is among the mostcommonly used local anesthetics from the amidegroup. Bupivacaine is considered to be more tox-ic than levobupivacaine or ropivacaine, which are

also from the amide group[1]. Anesthetics from theamide group affect both the central nervous system(CNS) and the cardiovascular system (CVS) andmay cause serious complications [2]. Generalisedtonic-clonic seizures (GTCS), myoclonus and sud-den death have been reported subsequent to theepidural administration, use for plexus block, and

erroneous intravenous (IV) administration of localanesthetics.

In our patient, we have administered bupiva-caine through the intrathecal route. Although gen-eralised myoclonic seizures have been reported inrelation with the intrathecal administration of bupi-

vacaine [3], according to our literature research, nostatus epilepticus in the form of GTC has yet beenreported in association with the intrathecal use ofbupivacaine. Thus, we would like to present a casewhere status epilepticus in the form of GTC has de-veloped subsequent to the intrathecal administra-tion of bupivacaine.

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CASE REPORT

In a 23-year old male patient who presented with ahistory of varicoceles, surgery under spinal anes-thesia was planned. The preoperative hemogram,biochemistry (glucose, creatinine, sodium, potas-

sium, calcium, urea, creatinine, aspartate amino-transferase (AST), alanine aminotransferase (ALT),electrocardiography (ECG), and chest X-ray werewithin normal limits. The systemic and neurologicexams of the patient were normal. The patient andfamily history included no evidence of epilepsy orany other chronic diseases. The spinal anesthe-sia was performed under routine monitorizationand through the insertion of a spinal catheter intothe vertebral space. The aspirated cerebro-spinaluid (CSF) was observed to be clear and withoutany trace of blood. Bupivacaine 12.5mg (marcaineheavy) was administered into the vertebral space inthe appropriate dose and duration. Soon after theinfusion of the medication, the patient complainedabout pain and contractions in the perineal region.The neurological examination of the patient carriedout 10-15 minutes later revealed that he was mildlyconfused and stereotypic and involuntary myoclonicmovements were occurring in his legs. In order toresolve the contractions in the perineal region andto achieve full anesthesia, 15 ml of 1% plirocaine(citanest) was injected into the incision area. Al-

though the contractions and the pain were relieved,since the patient was still slightly confused, he wasadministered 1mg/kg of propofol in order to achievefull anesthesia and to start the surgery. The op-eration was completed successfully. As the patientregained consciousness, just before he was fullyawake, he had a generalised tonic-clonic (GTC)epileptic seizure that continued for 2-3 minutes. Theseizure was stopped through the administration of10mg of intravenous (IV) diazepam (diazem). How-ever, about 6-8 minutes later, the GTC seizure re-started. Another 10mg dose of (IV) diazepam was

injected; but as the seizure continued, the patientwas given a 20mg/kg loading dose of valproatefollowed by a dose of 3mg/kg/min for 10 minutes.When the seizure still did not recede, the patientwas administered 1mg/kg of propofol. He was in-tubated and the infusion of propofol continued at adose of 1mg/kg/h. After 8 hours without seizures,the propofol dose was tapered and discontinued,and the patient was extubated. He was prescribed amaintenance dose of valproate and was followed upfor one month in terms of seizures and through elec-troencephalography (EEG). Since no seizure activ-

ity in the EEG or any clinical seizure was observed,the medication was discontinued. The patient was

followed up for ve months without medication andno seizures occurred during this period.

The patient’s blood test during the seizure wasas follows: WBC: 13.000 K/UL; creatinine: 1.6mg/dl; creatine kinase: >4000U/L. Other biochemi-

cal values were within normal limits. No cells weredetected in the cerebro-spinal uid and the proteinglucose was normal. The contrast cranial magneticresonance imaging (MRI), and the MRI venogra-phy and arteriography were also normal. The EEGtaken within the rst 24 hours showed a slow waveactivity originating from the bilateral frontal areas.The follow up EEGs were normal.

DISCUSSION

Our knowledge about the neurotoxicity of spinal lo-

cal anesthetics, which are being used in humans for100 years, is either based on personal experienceor a few small-scale studies. There is no large-scaleneurotoxicity study on spinal local anesthetics [4]. Ina study by Moen et al., the frequency of severe neu-rological complications with spinal local anestheticshas been found to be approximately 0.4/10000 [5]. Although this ratio does not constitute a high indi-vidual risk, it should not be overlooked that thesemedications may lead to severe neurological com-plications. Such a severe neurological complicationthat occurs subsequent to spinal local anesthesiacauses great stress for the patient and his/her fam-ily. Bupivacaine is one of the most frequently usedspinal local anesthetics from the amide group. Lo-cal anesthetics from the amide group may lead tosymptoms of the CNS such as depression, seizuresor altered mental state, while they may lead to ar -rhythmia in the CVS [6]. The relatively new levobu-pivacaine and ropivacaine have also been report-ed to induce GTC type of seizures when used forplexus blockage or epidural anesthesia [7, 8]. In ourcase, the altered mental state was observed a veryshort while after the administration of bupivacaineinto the vertebral space, followed by myoclonus inthe legs and stereotypical involuntary movements.Plirocaine was injected into the incision site of thepatient. In the wake of the surgery, status epilepti-cus in the form of a generalised tonic-clonic seizuredeveloped. Considering the timing and form of theevent, it can be inferred that the local anesthetic wasresponsible for the epileptic seizure. The causesof the neurologic complications observed with spi-nal local anesthetics are the administration of highdoses, rapid entry into the systemic circulation, er -

roneous administration through the IV route, or thediffusion of the drug towards the cephalic region [2].In our patient, the rapid entry of bupivacaine into

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the systemic circulation or a diffusion towards thecephalic region seem to be plausible explanationsfor the status epilepticus in the form of generalisedtonic-clonic seizures.

Case reports involving the loss of conscious-

ness, aphasia and automatism induced by theintrathecal administration of combined spinal an-esthetics that include fentanyl–bupivacaine orsunfentanyl-bupivacaine have been published.Loss of consciousness and aphasia that developedsubsequent to the intrathecal administration of sun-fentanyl-bupivacaine in an article by Franeto andFisher were found to be associated with opioids [9].However, a later article by Barbara M. reported of acase where the altered mental state and focal sei-zures with automatism observed subsequent to theadministration of fentanyl-bupivacaine could not be

stopped in spite of the twice I.V. administration of atotal dose of 160 μg naloxone, and thus the alteredmental state and focal seizures with automatismwere associated with bupivacaine [10]. In anotherstudy conducted on two volunteers, complicationsof the CNS including a transient loss of conscious-ness, muscle twitches, confusion, dysarthria andtinnitus developed after the I.V. infusion of bupiva-caine [11]. These reports show us that bupivacainemay cause epileptic seizures as well as variousneurological complications.

Since our patient was in a confused state andhad stereotypic and myoclonic movements in hislegs until he was sedated with propofol, the posi-tion of his head was changing rapidly. These posi-tion changes may have caused the drug to diffuse tothe cephalic region. The probability of the drugs todiffuse into the cephalic region has also been men-tioned in a study and it has been recommended toelevate the head to a 10° angle in order to reducethe diffusion [12].In our patient, the stereotypicaland myoclonic movements in the legs followed bythe GTC seizure that occurred soon after the infu-

sion of the bupivacaine into the vertebral space maypoint out that the drug may have spread towards thecephalic region and caused a GTC type of statusepilepticus.

Bupivacaine has been reported to cause myoc-lonus in the legs when used as a spinal anesthetic[3]. It is already known that, when injected into thevertebral space, local anesthetics may cause sub-acute spinal neuritis or myoclonus that occurs dueto the irritation of the inhibitor neurons in the mo-tor neurons. In a study conducted in animals, it hasbeen demonstrated that the small moderate thorn-like complexes in the amygdaloid nucleus, broughtabout by local anesthetics from the amide group de-

pending on the dose, may lead to generalised clon-ic seizures [13]. Our patient has also experiencedspasms in the perineal region, myoclonic twitches/ jerks and stereotypical movements in the legs justbefore the seizure started. Later, 15 ml of 1% pliro-

caine, which isalso a local anesthetic from the amide group,was injected to the incision site. We are of the opin-ion that the bupivacaine injected into the vertebralspace irritated the inhibitor neurons in the motorneurons and the plirocaine injected into the incisionsite entered the circulation and suppressed the ce-rebral cortex. Thus, the synergic effect of bupiva-caine and plirocaine has led to the status epilepti-cus.

In our patient, it is also possible that the bu-pivacaine may have entered the blood circulationto cause the GTC seizure. Although CSF has beenaspirated from the vertebral space and it was con-rmed that the injection was made into the vertebralspace and not intravenously, it is also known thatbupivacaine leads to vasodilatation when adminis-tered through the spinal route and thus increasesthe blood ow to the spinal cord [14]. Therefore, webelieve that bupivacaine increased the blood owto the spinal cord and thus entered the circulation.There are also case reports where bupivacainehas led to GTC seizures when accidentally injected

through the I.V. route [15]In conclusion, we would like to present this

case where the intrathecal administration of bupiva-caine led to a status epilepticus. In cases of statusepilepticus resistant to classical antiepileptics, toxiccauses must be investigated. Especially frequentlyused drugs affecting the central nervous systemmust be taken into consideration. It must also bekept in regard that a frequently used local anesthet-ic such as bupivacaine may lead to a status epilep-ticus when administered intrathecally.

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