|Year : 2013 | Volume
| Issue : 1 | Page : 10-17
Epilepsy and nonepilepsy surgery: Recent advancements in anesthesia management
Sukhminder Jit Singh Bajwa1, Ravi Jindal2
1 Department of Anaesthesiology and Intensive Care, Gian Sagar Medical College and Hospital, Ram Nagar, Banur, Patiala, Punjab, India
2 Department of Anaesthesiology and Intensive Care, Amar Hospital, Patiala, India
|Date of Web Publication||26-Jun-2013|
Sukhminder Jit Singh Bajwa
Department of Anaesthesiology and Intensive Care, Gian Sagar Medical College and Hospital, Ram Nagar, Banur, Punjab, House No-27-A, Ratan Nagar, Tripuri, Patiala, Punjab
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Epilepsy is one of the most common encountered neurological disorders. Surgical procedures in epileptic patient throw numerous challenges to the attending anesthesiologist during the perioperative period. Various anesthetic drug interactions with antiepileptics, intraoperative and postoperative seizures management and management of status epilepticus are few considerations which an anesthesiologist can confront both during emergency or elective surgery. The role of anesthesiologist acquires significant dimensions in management of epilepsy ranging from operative procedure, status epilepticus to the intensive care management of such patients. It requires a skilful and clinically precise handling of such patients during pre-op, peri-op and post-op period. Majority of times these patients present with co-morbidities which makes the prophylactic management of epilepsy extremely difficult during surgical procedures. The responsibilities of anesthesiologist involve management of epileptic patients not only during epilepsy and nonepilepsy surgery but for other diagnostic and therapeutic procedures as well where sedation or anesthesia services are required. Postoperative management of such patients include careful observation for any seizures and/or pseudo-seizures so as to manage appropriately. The knowledge regarding various antiepileptic agents and their potential side effects and interactions with anesthetic agents are of prime concern during surgical procedures for epilepsy and nonepileptic surgeries. The present article discusses the various anesthetic implications and considerations during management of such patients for epilepsy and nonepilepsy surgery.
Keywords: Anesthesia, epilepsy, pseudo-seizures, seizures, status epilepticus
|How to cite this article:|
Bajwa SJ, Jindal R. Epilepsy and nonepilepsy surgery: Recent advancements in anesthesia management. Anesth Essays Res 2013;7:10-7
| Introduction|| |
Epilepsy is the second most common neurological disorder, after stroke. The age-adjusted incidence in developed countries is 24-53 per 1,00, 000 person years. The incidence is higher in males and in lower socioeconomic class. In India the overall prevalence rate of epilepsy is 5.59 per 1000 population. ,, Management of an epileptic patient is a huge challenge for the attending anesthesiologist during the perioperative period. Various drug interactions of anesthetics with antiepileptics, intraoperative and postoperative seizures management and management of status epilepticus are few considerations which an anesthesiologist can confront both during emergency or elective surgery.
Classification of epileptic seizures
Epileptic seizures can be classified as partial, generalized, pseudoseizures, nonepileptic seizures and status epilepticus ,, [Table 1].
|Table 1: Showing the classification pattern of various seizure disorders|
Click here to view
Causes of epilepsy
It is extremely difficult to ascertain the exact cause of epilepsy and only in 25-35% of the patients, one can possibly be sure of the exact aetiology. , Following are few of the known causes of epilepsy:
In the developed countries predominant causes include developmental disorders and idiopathic causes in children and vascular and degenerative causes in adults, in the developing nations infections, parasites and trauma are the leading causes. 
- Genetic: Juvenile myoclonic epilepsy, benign rolandic epilepsy.
- Trauma: Depressed skull fractures or evidence of intracranial hemorrhage.
- Tumor: Epilepsy is more common with slow-growing tumors, anterior hemisphere tumors and may be generalized or focal in nature.
- Infection: Bacterial, fungal or tuberculous meningitis and viral encephalitis.
- Cerebral degeneration: Alzheimer's disease and multi-infarct dementia.
- Cerebrovascular disease: Cerebral infarction or hemorrhage.
- Multiple sclerosis.
- Alcohol: Lowers seizure threshold. Seizures may occur with binge drinking or withdrawal.
- Metabolic disorders: Hypocalcemia, hyper-calcemia, hypomagnesemia, hypoglycemia, hyponatremia and hypernatremia. Hepatic and renal failure can also precipitate seizures.
It is extremely essential to diagnose a case of epilepsy for an appropriate and timely therapeutic management. The diseases which are important for differential diagnosis of epilepsy includes syncope, transient ischemic attack, migraine, hyperventilation, narcolepsy, cataplexy, and nonepileptic seizures. 
Responsibilities of anesthesiologist in managing an epileptic patient
Managing a surgical epileptic patient is a huge challenging task for the attending anesthesiologist and requires a lot of skilful and knowledgeable measures on his part to evaluate completely and conduct safe anesthetic procedure.  The role of the anesthesiologist in case of epileptic patient acquires important dimensions which includes,
- Management of status epilepticus in the intensive care.
- Perioperative management for epilepsy surgery.
- Perioperative management for nonepilepsy surgery.
- Management of postoperative seizures in previously normal patient.
- Management of associated comorbid diseases.
Status epilepticus is one of the most dreaded medical emergencies which an anesthesiologist can encounter during emergency or elective surgery in a case of known epileptic patient. Status epilepticus can be defined as a continuous seizure activity lasting >30 min or intermittent seizure activity lasting >30 min during which consciousness is not regained. 
Status epilepticus should be managed as early as possible, preferably within 30 minutes. 
Management of status epilepticus
The diagnosis of status epilepticus is basically made on clinical grounds and the symptomatology is characterized by tonic-clonic seizures, loss of consciousness, tongue biting, urinary incontinence. ,,,, The management of status epilepticus should be initiated as early as possible and includes the following definite measures.
- ABC (Airway, breathing and circulation). Primary resuscitative measures to manage an attack of epilepsy are extremely important as these patients are at high risk of injury, airway compromise and other potential serious complications. These primary measures involves.
- Airway management.
- Administering 100% oxygen.
- Securing an IV access.
- Sending venous blood sample for biochemical analysis (including RBS).
- Closely monitoring the vital signs, ECG and SpO 2.
- Start IV infusion with normal saline. If hypoglycemia suspected or documented, give glucose. (adults: 100 mg thiamine IV followed by 50 ml of 50% glucose, children: 2 ml/kg of 25% glucose).
- First line therapy: IV Benzodiazipines - Lorazepam (0.1 mg/kg max 2 mg/kg upto 4 mg total dose) or Diazepam (0.1 mg/kg max 5 mg/kg upto 20 mg total dose).
- Second line therapy: IV Phenytoin (20 mg/kg max rate adults: 50 mg/min, children: 1 mg/kg/min) or Fosphenytoin (20 mg/kg Phenytoin equivalent (PE) @ 150 mg/min).
- If seizures persist: Additional phenytoin (5-10 mg/kg) or fosphenytoin (5-10 mg/kg PE).
- If seizures still persist: Phenobarbital 20 mg/kg (max @ 60 mg/min).
- Intubation and ventilation to maintain normal PaO 2 and PaCO 2 .
- Fluid resuscitation should be continued.
- If seizures remain uncontrolled propofol or thiopentone infusion. Taper infusions at 12 hours to observe further seizure activity.
Pharmacological therapy and possible drug interactions with anesthetics
Management of an epileptic patient, whether in operative suite or in intensive care unit always involve dedicated team efforts. However, the various drugs used to control epilepsy are not absolutely free from side effects and have their own complications. The current knowledge of potential interactions between anesthetic drugs and antiepileptic agents is limited to few percentage of medical fraternity. [Table 2] gives an elaborative review of the antiepileptic medications and their possible interactions with other drugs during the perioperative period. ,,,
|Table 2: Showing the indications, side effects and clinical actions/significance of various anti‑epileptic drugs|
Click here to view
Anesthetic management for epilepsy surgery
Surgical management may be indicated for cases with refractory epilepsy. It may be done to resect an epileptogenic focus or to interrupt a seizure pathway and includes 
- Temporal lobectomy.
- Extratemporal cortical excision.
- Corpus callosotomy.
- Vagal stimulation.
- Electrical stimulation of centromedian thalamic nucleus.
Anesthesia for epilepsy surgery may be required either in the form of general anesthesia or local anesthesia supplemented with sedation. The possible roles of an anesthesiologist during epilepsy surgery include: 
Besides the possible role in epilepsy surgery, the responsibilities of anesthesiologist also extend to the preoperative period. During the diagnostic interventions preoperatively the role of anesthesiologists includes 
- Monitored anesthesia care during awake craniotomy.
- Inducing intraoperative seizures for intraoperative electrocorticograhy.
- Brain protection, maintenance of intracranial hemodynamics and preventing rise in intracranial pressure.
- Rapid postoperative recovery to provide for early neurological assessment.
- Management of refractory seizures.
- Providing monitored anesthesia care for radiological procedures like magnetic resonance imaging and positron emission tomography.
- Monitored anesthesia care for stereotactic electrode insertion.
- General anesthesia for epidural electrode and grid placement.
- Thiopentone test for localisation of seizure focus. With gradual increase in thiopentone blood levels, β-activity occurs in normal neural tissue on electroencephalography while seizure focus shows abnormal response.
- Wada test is used to determine dominant cerebral hemisphere using amobarbital injected into carotid artery (to lateralize cerebral speech dominance).
Anesthetic management of patients with epilepsy involves numerous considerations preoperatively, perioperatively and during the postoperative period.
In addition to routine preanesthetic evaluation, one should assess for differential diagnosis of associated seizure disorders which can be attributed to various disease states such as Huntington's chorea, tuberous sclerosis, neurofibromatosis, lesch nyhan sundrome.  Similarly, possible anesthetic and antiepileptic drug interactions should be considered as hepatic enzyme induction can lead to requirement of higher doses of nondepolarizing muscle relaxants and opioids. The clinical history and examination should also include for the possible presence of various side effects of ongoing epileptics such as gingival hypertrophy, megaloblastic anemia and so on.
Premedicate with benzodiazepine, atropine or glycopyrrolate (as patients head and neck are inaccessible during intra-op period) and continue with anticonvulsants on the morning of surgery. 
Intraoperative monitoring includes electrocardiography, noninvasive blood pressure, pulse oximetery, end tidal carbon dioxide, temperature and urine output. Central venous pressure monitoring may be required if significant blood loss is anticipated. ,,
It is performed when epileptogenic focus is close to eloquent areas of the brain,  usually temporal lobe epilepsy. Electrocorticography (ECoG) may be used to identify the epileptogenic focus. However, anesthetics have a depressant effect on ECoG. Neurolept anesthesia (combination of droperidol and fentanyl) was traditionally used for management of anesthesia. However, the side effects include postoperative extrapyramidal excitation, unconsciousness, restlessness and confusion. Propofol is now the preferred agent. Alfentanil, remifentanil or fentanyl are used for intraoperative analgesia. Field block is used to provide local anesthesia.
For other surgeries where general anesthesia is used, induction may be done with thiopentone or propofol. Maintenance is done using nitrous oxide, narcotic and sub-MAC concentrations of isoflurane or sevoflurane.Early awakening allows rapid neurological assessment. Postoperatively pain relief is important. Blood levels of antiepileptics should be obtained to adjust the doses accordingly.
Anesthetic drugs and epilepsy
Numerous drugs used in anesthesia have potential drug interactions with anti-epileptic agents which can be highly detrimental during surgical procedures. ,,,
It is also used as first-line anticonvulsant drugs besides sedation purpose.
its antiepileptic activity is related to inhibition of pre and postsynaptic chloride channels mediated by GABA. It is used for sedation, induction and maintenance of general anesthesia. It can cause abnormal movements as opisthotonus and myoclonia in normal as well as epileptic patients.
It is anticonvulsant at high doses and proconvulsant at clinical doses.
At ususal doses it is epileptogenic and thus should be avoided.
It has no proconvulsant activity.
It has no pro or anticonvulsant activity. Sedation due to dexmeditomidine shows EEG pattern similar to stage II sleep. It is used in autistic children for EEG recording. However, this drug has numerous beneficial effects when used through different routes. It prolongs analgesia of local anesthetics when used in neuraxial blocks, attenuates pressor response when used before induction of anesthesia, reduces requirement of postoperative analgesics and causes reduction of shivering postoperatively after general anesthesia. ,,
It has been used in autistic patients for sedation during EEG recording. Its role is similar to dexmedetomidine when used through all the above mentioned routes but has lesser affinity at α-2 receptors as compared to dexmedetomidine. ,,
All barbiturates, except methohexitol, have significant anticonvulsant activity.
Mepiridine, due to its metabolite normeperidine, has proconvulsant activity. In patients with renal failure, advanced malignancy, sickle cell disease, prolonged use, enzymatic induction with anticonvulsants, normeperidine gets accumulated and can lead to seizures.
Morphine, though devoid of anticonvulsant activity, can cause tonic clonic activity when used in epidural space.
High doses of phenylpiperidine derivatives (fentanyl, alfentanil, sufenanil and remifentanil) should be avoided in epileptic patients.
Its epileptogenic potential is very low and can be safely used in epileptic patients.
Has a potent anticonvulsant activity.
Can cause epileptiform EEG and seizures, is contraindicated in epileptic patients.
Has potent anticonvulsant activity.
Avoid use at concentration above 1.5 MAC and in presence of hypocapnia.
Has no proconvulsant activity.
- Nondepolarizing blockers: Phenytoin and carbamazepine used chronically increases hepatic clearance of rocuronium, pancuronium, vecuronium, cisatracurium, decreasing their duration of action. Atracurium and mivacurium are not metabolised by hepatic enzymes and hence their duration if action is not affected. Acute administration of phenytoin potentiates the neuromuscular blockade of rocuronium. Though laudanosine, an atracurium metabolite has been postulated to be proconvulsant, yet there is no report of such episode in human beings.
- Depolarizing blocker succinylcholine: Its duration of action is slightly increased.
No reported proconvulsant activity.
Atropine, scopolamine and glycopyrrolate can be used in epileptics.
At subtoxic doses they are anticonvulsants, sedatives and analgesics while at higher concentrations can cause seizure activity.
Are of five main classes; dopamine antagonists, anticholinergics, antihistaminics, 5-HT 3 anatgonists, steroids. Dopamine antagonists (phenothiazines-prochlorperazine, butyrophenones-droperidol, benzamides-metoclopramide) can cause extrapyramidal effects and dystonia which can be confused with epileptic activity.
Anesthetic management for nonepilepsy surgery
Seizures occurring as a complication of anesthesia
- Preoperatively a careful review of medical history, factors triggering seizures (fasting, stress, sleep deprivation, alcohol, and drugs), comorbidities, mental retardation, hypotonia, risk factors for aspiration and difficult airway should be assessed. ,, Evaluation by a neurologist preoperatively is preferable. Anticonvulsants should be continued as scheduled on the day of surgery. Midazolam is usually used for premedication. However, some anticonvulsants and ketogenic diet can lead to sedation.
- Intraoperative monitoring depends upon the surgical procedure and the patients clinical condition.
- For induction propofol or thiopentone may be used. Ketamine and etomidate are best avoided. Opioids other than meperidine may be used. Total intravenous anesthesia (TIVA) with propofol and fentanyl can also be used safely in such patients. [Ref ] Neuraxial opioids can also be safely used.
- Avoid intraoperative hypoxia, hypotension, hypocapnia and hyponatremia.
- Regional anesthesia can be safely used. Coagulation profile, however, should be assessed because of propensity of certain anticonvulsants to precipitate coagulation disturbances.
- Postoperatively anticonvulsants should be started as early as possible. If fasting time is 12-14 hours, parenteral replacement for oral drugs may not be required. However, where fasting time exceeds 24 hours parenteral replacement is necessary.
Postoperative seizures, though rare, are a recognized complication of anesthetics. ,, Patients at risk are generally those who already have epilepsy, especially those with poor preoperative control and those undergoing brain surgeries. Rarely seizures can occur as isolated event in previously normal patient. This should prompt search for structural or chemical brain abnormality.
Risk factors for seizures postperatively
Vigil has to be exercised during post-operative period as numerous risk factors listed below can be potential cause of seizures. 
Perioperative seizures, if prolonged, can cause brain damage due to hypoxia, apnea, prolonged postoperative mechanical ventilation, and delayed awakening from anesthesia. Physiological cardiac and respiratory regulation may be impaired. There may be tachycardia and tachypnea, apnea and bradycardia or sudden death due to autonomic instability, which causes cardiac arrhythmias or neurogenic pulmonary edema. 
- Pre-existing epilepsy or seizure disorder, especially if poorly controlled.
- Lengthy surgery or surgery that lasts longer than the effectiveness of the last dose of seizure medication in epileptics.
- Pre-existing brain abnormality such as tumor, aneurysm or scarring.
- Alcoholism and alcohol withdrawal.
- Illicit drug use.
- Local anesthesia in large doses.
- Certain anesthetics in combination with any of the above.
- Chemical or electrolyte abnormality.
Management includes maintaining a patent airway with adequate ventilation and protect the patient from injuries resulting from seizures. Monitoring should be performed using cardioscope, blood pressure and pulse oximetry. 
Should convulsions persist for more than 5 minutes, intravenous benzodiazepine should be used. Preffered drug is lorazepam. Alternatively diazepam (5-20 mg) may be used. If convulsions persist, a second dose of benzodiazepine with phenytoin (20 mg/kg over 30 minutes) may be used. For refractory seizures, phenobarbital (1.5 mg/kg/min or 100 mg/70 kg/min can be used with a maximum dose of 20 mg/kg or 1,000 mg/70 kg), midazolam (0.1-0.3 mg/kg in 2-5 minutes, followed by infusion of 0.05 to 0.4 mg/kg/hour), propofol (1-2 mg/kg followed infusion of 2-10 mg/kg/h), thiopental (5-10 mg/kg in 10 minutes, followed by infusion of 100-400 mg/h), lidocaine (1.5-2 mg/kg in 2-5 minutes, followed by infusion of 2-3 mg/kg/h for 12 hours), isoflurane (0.5-1.5%) and ketamine (50-100 mg followed by infusion of 50-100 mg/h). 
Postoperative pseudo-epileptic seizures
Postoperative shivering is common complication of anesthesia. Various drugs and adjuvants have been successfully used during peri-op period for the prevention of postoperative shivering.  It can be confused with epileptic seizures. Some anesthetic drugs can cause dystonic movements or epileptiform activity, but drug-induced seizures are rare. Postoperative seizures are more common after neurosurgery. Pseudo-epileptic seizures in the postoperative period resemble tonic-clonic seizures but are not associated with abnormal electrical discharges in the brain.  They tend to be associated with a history of convulsions and/or psychosomatic illness. They are characteristically flamboyant, last longer than 90 s and are associated with asynchronous limb movements, side-to-side head movements, closed eyes (including a resistanxce to eye opening) and maintenance of papillary reflexes. There is no cyanosis or postictal period but there may be incontinence or tongue-biting. Seizures may settle with reassurance. Plasma prolactin concentrations tend to be raised after epileptic seizures and normal after pseudo-seizures. However, the diagnosis of pseudo-seizures remains primarily clinical. It is possible for both epileptic and pseudo-epileptic seizures to coexist.
| References|| |
|1.||Bhagat H, Dash HH. Anaestehsiologist's role in the management of an epileptic patient. Indian J Anaesth 2006;50:20-6. |
|2.||Porter RJ. Classification of epileptic seizures and epileptic syndromes. In: Laidlaw J, Richens A, Chadwick D, editors. A textbook of epilepsy. New York: Churchill Livingstone, 1993. p. 1. |
|3.||Hauser WA. Incidence and prevalence. In: Engel Jr J, Pedley TA, editors. Epilepsy: A comprehensive textbook. Philadelphia: Lippincott- Raven; 1997. p. 47-57. |
|4.||Maranhao MV, Gomes EA, Carvalho PE. Epilepsy and Anesthesia. Rev Bras Anestesiol 2011;61:232-41. |
|5.||Gratrix AP, Enright SM. Epilepsy in anaesthesia and intensive care. Continuing Education in Anaesthesia, Critical Care and Pain. 2005;5:118-21. |
|6.||Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010;51:676-85. |
|7.||Kofke WA. Anesthetic management of the patient with epilepsy or prior seizures. Curr Opin Anesthesiol 2010;23:391-9. |
|8.||Meierkord H, Boon P, Engelsen B, Göcke K, Shorvon S, Tinuper P, et al. EFNS guideline on the management of status epilepticus in adults. Eur J Neurol 2010;17:348-55. |
|9.||Mirsattari SM, Sharpe MD, Young R. Treatment of refractory status epilepticus with inhalational anesthetic agents isoflurane and desflurane. Arch Neurol 2004;61:1254-9. |
|10.||Power KN, Flaatten H, Gilhus NE, Engelsen BA. Propofol treatment in adult refractory status epilepticus. Mortality risk and outcome. Epilepsy Res 2011;94:53-60. |
|11.||Mo¨ddel G, Bunten S, Dobis C, Kovac S, Dogan M, Fischera M, et al. Intravenous levetiracetam: A new treatment alternative for refractory status epilepticus. J Neurol Neurosurg Psychiatry 2009;80:689-92. |
|12.||Modica PA, Tempelhoff R, White PF. Pro- and anticonvulsant effects of anesthetics (Part I). Anesth Analg 1990;70:303-15. |
|13.||Saboory E, Derchansky M, Ismaili M, Jahromi SS, Brull R, Carlen PL, et al. Mechanisms of morphine enhancement of spontaneous seizure activity. Anesth Analg 2007;105:1729-35. |
|14.||Ubogu EE, Sagar SM, Lerner AJ, Maddux BN, Suarez JI, Werz MA. Ketamine for refractory status epilepticus: A case of possible ketamine-induced neurotoxicity. Epilepsy Behav 2003;4:70-5. |
|15.||Holtkamp M. The anaesthetic and intensive care of status epilepticus. Curr Opin Neurol 2007;20:188-93. |
|16.||Aylward RL. Epilepsy: A review of reports, guidelines, recommendations and models for the provision of care for patients with epilepsy. Clin Med 2008;8:433-8. |
|17.||Bajwa SJ, Bajwa SK, Kaur J, Singh G, Arora V, Gupta S, et al. Dexmedetomidine and clonidine in epidural anaesthesia: A comparative evaluation. Indian J Anaesth 2011;55:116-21. |
|18.||Bajwa SS, Kaur J, Singh A, Parmar SS, Singh G, Kulshrestha A, et al. Attenuation of pressor response and dose sparing of opioids and anaesthetics with pre-operative dexmedetomidine. Indian J Anaesth 2012;56:123-8. |
|19.||Bajwa SJ, Gupta S, Kaur J, Singh A, Parmar SS. Reduction in the incidence of shivering with perioperative dexmedetomidine: A randomized prospective study. J Anaesthesiol Clin Pharmacol 2012;28:86-91. |
|20.||Bajwa SJ, Kaur J, Bajwa SK, Bakshi G, Singh K, Panda A. Caudal ropivacaine-clonidine: A better post-operative analgesic approach. Indian J Anaesth 2010;54:226-30. |
|21.||Bajwa SJ, Bajwa SK, Kaur J, Singh A, Singh A, Parmar SS. Prevention of hypotension and prolongation of postoperative analgesia in emergency cesarean sections: A randomized study with intrathecal clonidine. Int J Crit Illn Inj Sci 2012;2:63-9. |
|22.||Ng L, Chambers N. Postoperative pseudoepileptic seizures in a known epileptic: Complications in recovery. Br J Anaesth 2003;91:598-600.Ni |
[Table 1], [Table 2]