CLINICAL REPORT Intracarotid Etomidate is a Safe Alternative to Sodium Amobarbital for the Wada Test Ramamani Mariappan, MD,* Pirjo Manninen, MD, FRCPC,* Mary P. McAndrews, PhD,w Melanie Cohn, PhD,w Peter Tai, MD, FRCPC, Taufik Valiante, MD, PhD, FRCS(C),y and Lashmi Venkatraghavan,z MD, FRCA, FRCPC* Conclusion: From our experience, etomidate is a safe alternative Background: The Wada procedure (the intracarotid amobarbital to sodium amobarbital for the Wada test for determining the procedure) has been used widely to evaluate the hemispheric hemispheric dominance for speech and in predicting the memory dominance of language and memory before temporal lobe sur- outcome. gery in patients with medically refractory seizures. Because of repeated shortage of sodium amobarbital, attempts have been Key Words: Wada test, sodium amobarbital, intracarotid eto- made to find a suitable alternative to sodium amobarbital. The midate injection, EEG and motor effects, language and speech aim of our study was to review our experience with the use of lateralization etomidate as an alternative to sodium amobarbital for Wada (J Neurosurg Anesthesiol 2013;00:000–000) testing in patients with medically refractory seizures. Methods: After the ethics approval, we retrospectively reviewed the charts of 29 consecutive patients who underwent Wada test he Wada procedure, also known as the intracarotid with etomidate. Data from a total of 50 hemispheric injections Tamobarbital procedure (IAP), has been used for >50 were reviewed and analyzed. This included the electro- years to evaluate language laterality and to predict the encephalographic and motor effects of etomidate injection and postoperative memory outcome in the surgical planning of their time course (onset and recovery), Wada test results (lan- patients with medically refractory temporal lobe epilepsy.1,2 guage laterality and memory performance), and all adverse The basic methodology of IAP is to inject a short-acting events during the procedure. intravenous (IV) anesthetic agent into the carotid artery to Results: Intracarotid administration of etomidate produced a anesthetize ipsilateral hemisphere, allowing one to assess the predictable electroencephalographic and motor effects in all language and memory functions of the contralateral hemi- sphere in isolation. Sodium amobarbital has been the patients. The desirable effect was seen with a single bolus dose of 1,2 2 mg followed by an infusion. Shivering was the most common standard drug used for IAP for >50 years. In most cen- side effect, seen in all the patients. Successful testing was possible ters, anesthesiologists were not usually present during this in nearly all patients without any major side effects. The “pass procedure and the radiologist usually injected the sodium rate” of valid tests was in good accord with our previous amobarbital. Because of frequent interruptions with the experience with the use of sodium amobarbital. supply and limited availability of sodium amobarbital, vari- ous anesthetic agents have been tried for this procedure, and hence, anesthesiologists are now being involved in this pro- cedure.3–9 The use of etomidate in IAP was developed by the Received for publication December 28, 2012; accepted April 11, 2013. Epilepsy Surgical Program at the Montreal Neurological From the Departments of *Anesthesia; wPsychology; Divisions of Institute, in which it was reported to be an effective alter- Neurology; and yNeurosurgery, Toronto Western Hospital, Uni- versityz Health Network, University of Toronto, Toronto, ON, native to sodium amobarbital, referring to the procedure as Canada. the etomidate speech and memory (eSAM) test.9 Intracarotid R.M.: helped with the analysis of the data, to write the manuscript, and administration of anesthetic agents poses unique pharmaco- approved the final manuscript; P.M.: helped to write the manuscript kinetic challenges for anesthesiologists. The purpose of this and approved the final manuscript; M.P.M.: helped to write the manuscript and approved the final manuscript; M.C.: helped with the study was to review our experience with the use of etomidate analysis of the data and approved the final manuscript; P.T.: helped as an alternative to sodium amobarbital for Wada testing in to write the manuscript and approved the final manuscript; T.V.: patients with medically refractory epilepsy. helped to write the manuscript and approved the final manuscript; L.V.: helped to conduct the study, analyze the data, write the manuscript, and approved the final manuscript. METHODS The authors have no funding or conflicts of interest to disclose. Reprints: Lashmi Venkatraghavan, MD, FRCA, FRCPC, Department Subjects of Anesthesia, Toronto Western Hospital, University Health Net- work, University of Toronto, 399 Bathurst Street, Toronto, ON, After the institutional research and ethics board Canada M5T 2S8 (e-mail: [email protected]). approval, we retrospectively reviewed the clinical, electro- Copyright r 2013 by Lippincott Williams & Wilkins encephalographic (EEG), and neuropsychological data of | J Neurosurg Anesthesiol Volume 00, Number 00, ’’ 2013 www.jnsa.com 1 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Mariappan et al J Neurosurg Anesthesiol Volume 00, Number 00, ’’ 2013 29 consecutive patients (one of whom underwent 2 proce- memory performance), and all complications during the dures) who underwent eSAM in our institution from Jan- procedure. Analysis of EEG changes included the time of uary 2007 to December 2011. All patients in our institution onset and recovery of slow wave activity in response to undergo extensive presurgical evaluation, consisting of etomidate infusion, the presence of sharp wave activity, noninvasive and invasive investigations (where required) and the contralateral spread of the slow wave activity. A before the surgical treatment for their medically refractory descriptive statistical analysis was performed using the epilepsy. Language dominance is usually determined by Statistical Package for the Social Sciences version 20. All functional magnetic resonance imaging (fMRI). Generally, values are expressed as mean ± SD. patients who are deemed to be at risk of drastic post- operative memory dysfunction are referred for IAP. RESULTS Procedure Atotalof29patientsunderwent50hemisphericin- jections. The demographic data are as shown in Table 1. All The procedures were performed in the neuro- patients received a 2-mg bolus of etomidate followed by the radiology suite. Patients were monitored with electro- infusion of 12 mg/h. The average duration of infusion was cardiography, noninvasive blood pressure monitoring, 3minutes26seconds(rangefrom2min46sto3min56s) and pulse oximetry. All patients had continuous mon- with a mean dose of 2.68 mg (dose range from 2.55 to itoring of 24-channel EEG. An anesthesiologist ad- 2.78 mg). Sixteen patients also had an injection of the ministered the drug and monitored the patient. A contralateral hemisphere (bilateral injection) to test the neuropsychologist performed the motor, language, and functional adequacy of the to-be-resected temporal lobe. In memory assessments during the procedure. 4patients,thetestwasrepeatedonthesamesidetoconfirm Under local anesthesia, the femoral artery was can- the validity of the first test because of initial poor contact nulated using a 5-F catheter with a dead space of 1.2 mL. with the patient, strong emotional reaction preventing full The catheter was advanced into the internal carotid artery engagement, failure of the preinjection items, and an un- until the tip of the catheter was at the level of the first usual delayed effect of etomidate. In patients who had bi- cervical (C1) vertebral body. A cerebral angiogram was lateral injections (n = 16), the average time between the first performed to confirm the absence of any significant cerebral and the second injections was 26 ± 7 minutes. cross-flow or abnormal vascularcirculation.Inallexcept1 case, the first injection was administered in the hemisphere EEG Effects After Etomidate Injection with the seizure focus to test the contralateral hemisphere, Immediately after the injection of etomidate, all thus mimicking surgery. Before the injection, patients were patients showed EEG slowing with delta and/or theta presented with 5 pictures of objects that they were to re- waves on the ipsilateral side. The onset of EEG slowing member. Etomidate 2 mg (2 mg/mL) was injected as a bolus was at 29.46 ± 12.69 seconds after the bolus, and the over 30 seconds using a syringe driver infusion pump recovery to baseline was 374.26 ± 170.19 seconds after (Medfusion 3500; Smith Medical MD Inc., St. Paul, stopping the infusion. Contralateral hemispheric EEG Minnesota) followed by an infusion of 6 mL/h (12 mg/h) slowing was also noticed in 9 patients. This slowing was etomidate. After the onset of contralateral hemiplegia, ad- observed mainly in the frontal areas (n = 9) and in some equate contact with the patient was verified by the execution patients (n = 5) in the parasagittal and temporal areas. of a simple verbal command or by observing the patient’s After the second injection, the onset of EEG effect was visually orienting or tracking stimuli. Then, all the memory earlier (24.2 ± 8.73 s) and the recovery was delayed items (10 common objects that were to be named) were (454.90 ± 184.39 s) compared with the first injection shown. The infusion was then stopped and from this point (Figs. 1, 2). This was not statistically significant. forward,