Intracarotid Etomidate Is a Safe Alternative to Sodium Amobarbital for the Wada Test

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 hemisphere 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 procedure.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

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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 postoperative 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, language (reading, naming, repetition, spelling, Intracarotid injection of etomidate produced an and counting) and motor functions were sampled re- increase in the interictal epileptiform activity in 70% of peatedly. Once the patient recovered from the drug effect, all the injections (35/50). This increased interictal spikes both clinically and electrophysiologically, a yes-no recog- appeared almost immediately after etomidate injection nition memory test was performed, which consisted of the and was simultaneous with the EEG slowing. In all pa- presentation of the 10 old objects and 10 new (distractor) tients, interictal spiking was seen only after ipsilateral objects. Patients were also tested with the preinjection 5 items to ensure that the testing was valid. Memory was considered adequate (pass) when Z70% of the objects TABLE 1. Demographics shown during the drug effect were recognized and 90% of Total no. patients/hemispheric injections 29/50 the distractors were rejected. If indicated, the second test Age (y) (mean ± SD) 35 ± 11 was then performed in a similar manner on the other side. Sex (male:female) 13:16 Diagnosis (TLE:brain tumor) 28:1 Handedness (right:left) 28:1 Data Analysis Hemispheric dominance (left:right) 27:2 Data from a total of 50 hemispheric injections were Epileptic side (left:right) 18:11 reviewed and analyzed. This included the EEG and motor Injection (unilateral:bilateral) 14:16 effects of etomidate injection and their time course (onset TLE indicates temporal lobe epilepsy. and recovery), eSAM test results (language laterality and

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FIGURE 1. The onset time [mean ± SD (s)] of electroencephalographic (EEG) and motor effects after the first and the second injections.

injection to the epileptogenic side, except in 1 patient who Neuropsychological Assessment had bilateral interictal epileptiform activity after unilat- Neuropsychological assessments were considered to eral injection. be valid in 44 (88%) injections. They were considered to be invalid in 6 injections (5 patients) because of vomiting (n = 1), bilateral EEG effects and poor contact (n = 2, but in the same patient), failure to recognize preinjection Motor Effects After Etomidate Injection items (n = 1), adverse emotional reaction (n = 1), and All patients had contralateral hemiplegia after in- delayed effect of etomidate (n = 1). In 4 patients, the test jection. The onset of motor and EEG effects occurred was repeated and valid data were obtained. simultaneously, but the recovery times were different (Figs. 1, 2). The onset of motor effect was seen at 29.7 ± 15.4 seconds after the bolus and the recovery to Language grade 5 power was seen 558 ± 208 seconds after stopping Language dominance had been established pre- the infusion. The onset (26.75 ± 10.46 s) and recovery viously in most patients using fMRI: 25 were left domi- (543 ± 188 s) of the motor effect was earlier after the nant, 2 were right dominant, and 2 were unable to second injection compared with that of the first injection. complete the fMRI paradigms. The eSAM test results This was not statistically significant. were concordant with fMRI data. Speech arrest followed

FIGURE 2. The recovery time [mean ± SD (s)] of electroencephalographic (EEG) and motor effects after the first and the second injections.

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Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Mariappan et al J Neurosurg Anesthesiol Volume 00, Number 00, ’’ 2013 injection in the dominant hemisphere in 14 patients, with duration of action (5 to 10 min) with minimal hemody- full recovery of language by 438 ± 138 seconds (range 238 namic effects. In our study, intracarotid administration of to 660 s). etomidate produced predictable EEG and motor effects (ipsilateral EEG slowing, contralateral hemiplegia) in all Memory and Outcome patients. The desirable effects were seen with a single In our study, 24 patients passed the test and 5 failed bolus dose of 2 mg followed by an infusion. Successful the test. Currently, 19 patients have undergone standard testing was possible in nearly all patients without any temporal lobe resections. Of 19 patients, 14 have under- major side effects. The “pass rate” of valid tests was in gone a 1-year postoperative neuropsychological testing good accord with our previous experience with the use of (dominant hemisphere resection, n = 8; nondominant, sodium amobarbital. Our findings are also in agreement 9 n = 6). None of the patients developed a severe post- with those of Jones-Gotman et al who pioneered the use operative memory deficit or speech disturbance. of etomidate for IAP. Intracarotid administration of anesthetic agents has Adverse Events a different pharmacokinetic profile compared with the IV No hemodynamic changes were noted with the in- route.13 The ideal pharmacokinetic properties of the drug tracarotid administration of etomidate except in 1 pa- used for the Wada test should have a short duration of tient. This patient had significant nausea and vomiting action (around 15 min) to allow adequate time for lan- immediately after the injection of etomidate accompanied guage and memory testing without multiple dosing. It by tachycardia (110 beats/min) and hypertension (140/ should also have very minimal residual effect on con- 90 mm Hg) that lasted for 3 minutes. This episode was sciousness, to allow multiple tests in a single session. attributed to a possible electrographic seizure and he Finally, it should produce consistent effects both clinically could not complete the test on that day. He successfully and electrophysiologically without any epileptogenic pro- completed the test on another day under antiemetic properties or other side effects. Sodium amobarbital was the phylaxis with 2 mg IV granisetron. Shivering was the most standard drug used in the Wada test for many decades common side effect and was seen in all patients. In 50% of because of its short duration of action and low toxicity, as the patients, the shivering was severe, but oxygen satu- well as clinicians’ extensive experience with its drug ration was maintained (>94%) in all patients without effects. Recently, the supply of sodium amobarbital has supplemental oxygen. In contrast to myoclonic jerks, been disrupted worldwide and has led to exploration of shivering involved predominantly the extremities and was other possible agents. Pentobarbital, methohexital, seco- self-limiting, lasting only for a few minutes. barbital, etomidate, and propofol have all been inves- Mood changes were seen in 23% of the patients and tigated as substitutes.3–9 The summary of anesthetic consisted of both positive and negative mood experience. agents used for the Wada procedure is shown in Table 2. In 3 patients, these were quite extreme, involving agi- The use of propofol as an alternative to sodium tation and/or sobbing that occurred rather late in the amobarbital has been studied extensively. However, the procedure; 2 patients required small doses (20 mg) of IV incidence of adverse reactions reported in the literature propofol to sedate them. were very high with propofol, most patients experiencing significant eye pain, facial and ocular flushing, tonic posturing, and conjugate eye deviation. DISCUSSION The intracarotid administration of drugs has unique Fifty years ago, Wada1 first introduced the concept of pharmacokinetic challenges. All the drugs used for in- intracarotid sodium amytal injection for the purpose of tracarotid injection have been administered as single speech lateralization. Sincethen,numerousefforts have or multiple boluses by hand injection. The intra-arterial been made to identify a minimally invasive method for dose of anesthetic agents is 1/10th of the IV dose,13 and determining language and memory dominance without this usually does not vary with the patient’s weight. sacrificing accuracy.10 For language testing, fMRI has been The volume of the drug used for injection varies from shown to identify language dominance with 95% accu- 3 mL (sodium amobarbital) to 10 mL (pentobarbital). racy.10 Therefore, the use of the Wada procedure for the Etomidate is very unique in that the intra-arterial dose is sole purpose of language lateralization is seldom justified. 2 mg or 1 ml of the standard concentration, and in our The postoperative memory outcome can be predicted by experience, any dilution of the drug failed to produce the standardized neuropsychological testing in most patients desired clinical effects. As the intra-arterial dose of eto- with unilateral temporal lobe epilepsy.11 However, there is midate is 1 mL (2 mg), flushing the catheter dead space no alternative to the Wada procedure to assess the risk of after the bolus will dilute the drug and abolish the clinical severe postoperative memory loss in individuals with evi- effects. Hence, etomidate needs to be injected undiluted as dence of bitemporal disease or dysfunction. a 1 mL (2 mg) bolus using an infusion pump followed by a Etomidate, an imidazole derivative, is a potent maintenance infusion to prevent the dilution of the drug nonbarbiturate hypnotic agent with no analgesic prop- from the flushing of the angiographic catheter. erties.12 Its anesthetic effects are mediated through the The clinical and EEG effects of intracarotid etomidate modulation of g-amino butyric acid (GABA) A re- were comparable to those of sodium amobarbital. The onset ceptors.12 It has a rapid onset (30 to 60 s) and a short of EEG and motor effects after etomidate injection occurred

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TABLE 2. Summary of Anesthetic Agents Used for the Wada Test Agent (Concentration) Dose Comments References Amobarbital (25 mg/mL) 75-125 mg followed by Gold standard. Short duration of action, low toxicity, Wada and colleagues1–4,14 25 mg extensive clinical experience Methohexital (1 mg/mL) 3 mg followed by 2 mg Very short duration of action—need for multiple boluses Buchtel, Andelman, Loddenkemper and Fluctuating levels of drug effect—reliability of the test colleagues6,7,14–16 questionable. Electroencephalographic changes are brief and less obvious—the drug effect is monitored by clinical means (motor and speech) Increased incidence of seizures Propofol (1 mg/mL) 10-20 mg followed by Short duration of action—need for multiple boluses Mikati, Takayama and 10 mg Fluctuating levels of drug effect—reliability of the test colleagues4–6,17 questionable Lipid emulsion—pain and discomfort on injection Severe side effects—confusion, head and eye version and myoclonic movements, ipsilateral facial, and ocular flushing Pentobarbital (2 mg/mL) 20-24 mg followed by Very long duration of action Kim and colleagues3,6 12-16 mg Report of transient respiratory depression needing endotracheal intubation Secobarbital (5 mg/mL) 10-25 mg Effects similar to amobarbital with minimal side effects Yamaguchi et al8 Ideal substitute for amobarbital Not widely available Etomidate (2 mg/mL) 2 mg bolus followed by Effects similar to amobarbital Jones-Gotman and 12 mg/h Small volume of drug—need for an infusion pump to colleagues6,9 deliver the undiluted drug Infusion can maintain the level of anesthesia for longer period Shivering is the major side effect

simultaneously. The onset of EEG slowing was earlier and the injection of cold drug into the brain, activating cold recovery was delayed after the second-side injection (on the responses from the hypothalamus. Because of this, in nonepileptogenic side) comparedwiththeepileptogenicside some centers, sodium amytal was prewarmed routinely (first-side injection). This difference may be due to the var- before injection. However, Shah et al23 have reported that iation in distribution of GABA and benzodiazepine re- shivering was more likely to follow sodium amobarbital ceptors in the epileptogenic and nonepileptogenic cortex.18 It injection if there was no filling of the posterior circulation has been shown that there is a reduction in the number of on a cerebral angiogram. They postulated that a transient these receptors in the epileptogenic area of patients with but selective functional lesion of the anterior hypothal- temporal lobe epilepsy.19–21 As etomidate acts on GABA amus produced by the effects of sodium amobarbital may receptors, delayed onset and early recovery after injecting result in disinhibition of the posterior hypothalamus into the epileptogenic side may be due to the decreased and other brainstem thermoregulatory centers, thereby number and affinity of GABA receptors on this hemisphere inducing transient shivering.23 compared with the normal nonepileptogenic side. Transient mood changes were observed infrequently In the seminal study by Jones-Gotman and col- during the procedure. In our study, 3 patients became very leagues, the contralateral (second) injection was carried restless and agitated, especially after the second injection, out on a separate day to avoid potential interactions with needing sedation to calm them; several others showed less the first injection.9 However, in addition to the time and drastic effects involving sobbing or laughter. Etomidate can cost, each procedure of transfemoral cerebral angio- cause activation of interictal epileptiform activity and also graphy carries a risk of stroke and other morbidity.22 electrographic or clinical seizures.24,25 In our study, in- Thus, our decision was to perform both hemispheric increased interictal activity was seen in 28 injections, but there jections at the same setting. With sodium amobarbital, it were no clinical seizures. Adrenal suppression has been re- has been recommended to wait for 45 minutes between ported even with a single dose of etomidate injection.26,27 injections. In our study, the average time between the first However, this was in settings where the etomidate dose was and second injection was 25 minutes (range, 13 to 39 min). 10 times that used in the eSAM test. Shivering was the most common side effect seen Although the outcome data from postoperative during this procedure. It has also been reported with neuropsychological testing are based on only half of the other anesthetic agents. One study quotes 46% incidence patients who underwent eSAM, it is important to note of transient shivering with amobarbital.23 The exact that the test validity appears good. That is, none of the mechanism of shivering is not known. One of the postu- patients developed a severe postoperative memory deficit lated mechanisms was that shivering may be caused by (thus excellent specificity) and those who did poorly on

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Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Mariappan et al J Neurosurg Anesthesiol Volume 00, Number 00, ’’ 2013 the contralateral injection showed less change after the 11. Pelletier I, Sauerwein HC, Lepore F, et al. Non-invasive alternatives surgery (therefore good sensitivity). to the Wada test in the presurgical evaluation of language and memory functions in epilepsy patients. Epileptic Disord. 2007;9: 111–126. CONCLUSIONS 12. Forman SA. Clinical and molecular pharmacology of etomidate. From our experience, etomidate is a safe alternative Anesthesiology. 2011;114:695–707. 13. Joshi S, Meyers PM, Ornstein E. Intracarotid delivery of drugs: the to sodium amobarbital for the Wada test for determining potential and the pitfalls. Anesthesiology. 2008;109:543–564. the hemispheric dominance for speech and in predicting 14. Loddenkemper T, Mo¨ ddel G, Dinner DS, et al. Language assess- the memory outcome. Intracarotid administration of ment in Wada test: comparison of methohexital and amobarbital. etomidate produced predictable EEG and motor effects Seizure. 2009;18:656–659. (ipsilateral EEG slowing, contralateral hemiplegia) in all 15. Andelman F, Kipervasser S. Reider-Groswasser. Hippocampal memory function as reflected by the intracarotid sodium methohex- patients. Successful testing was possible in nearly all the ital Wada test. Epilepsy Behav. 2006;9:579–586. patients without any major side effects. The “pass rate” of 16. LoddenKemper T, Moddel G, Schuele SU, et al. Seizures during valid tests was in good accord with our previous experi- intracarotid methohexital and amobarbital testing. Epilepsy Behav. ence with the use of sodium amobarbital. 2007;10:49–54. 17. Mikuni N, Takayama M, Satow T, et al. Evaluation of adverse effects in intracarotid propofol injection for Wada test. Neurology. REFERENCES 2005;65:1813–1816. 1. Wada JA. A new method for the determination of the side of 18. Johnson EW, de Lanerolle NC, Kim JH, et al. “Central” and cerebral speech dominance. A preliminary report of the intra-carotid “peripheral” benzodiazepine receptors: Opposite changes in human injection of sodium amobarbital in man. Igaku to Seibutsugaki, epileptogenic tissue. Neurology. 1992;42:811–815. Tokyo. 1949;14:221–222. 19. Mcdonald JW, Garofalo EA, Hood T, et al. Altered excitatory 2. Wada J, Rasmussen T. Intracarotid injection of sodium amobarbital and inhibitory amino acid receptor binding in hippocampus for the lateralization of cerebral speech dominance. J Neurosurg. of patients with temporal lobe epilepsy. Ann Neuro. 1991;29: 1960;17:266–282. 529–541. 3. Kim JH, Joo EY, Han SJ, et al. Can pentobarbital replace 20. Burdette DE, Dakurai SY, Henry TR, et al. Temporal lobe central amobarbital in the Wada test? Epilepsy Behav. 2007;11:378–383. benzodiazepine binding in unilateral mesial temporal lobe epilepsy. 4. Mikati MA, Naasan G, Tarabay H, et al. Intracarotid propofol Neurology. 1995;45:934–941. testing: a comparative study with amobarbital. Epilepsy Behav. 21. Henry TR, Frey KA, Sackellares JC, et al. In vivo cerebral 2009;14:503–507. metabolism and central benzodiazepine-receptor binding in tempo- 5. Takayama M, Miyamoto S, Ikeda A, et al. Intracarotid propofol ral lobe epilepsy. Neurology. 1993;43:1998–2006. test for speech and memory dominance in man. Neurology. 2004;63: 22. Loddenkemper T, Morris HH, Moddel G. Complications during the 510–515. Wada test. Epilepsy Behav. 2008;13:551–553. 6. Patel A, Wordell C, Szarlej D. Alternatives to sodium amobarbital 23. Shah AK, Atkinson MD, Gupta P, et al. Transient shivering during in the Wada test. Ann Pharmacother. 2011;45:395–401. Wada test provides insight into human thermoregulation. Epilepsia. 7. Buchtel HA, Passaro EA, Selwa LM, et al. Sodium methohexital 2010;51:745–751. (brevital) as an anesthetic in the Wada test. Epilepsia.2002;43: 24. Ebrahim ZY, DeBoer GE, Luders H, et al. Effect of etomidate on 1056–1061. the electroencephalogram of patients with epilepsy. Anesth Analg. 8. Yamaguchi T, Shojima M, Delashaw BJ, et al. Wada test using 1986;65:1004–1006. secobarbital sodium (Ional) to determine language dominance. Br J 25. Krieger W, Copperman J, Laxer KD. Seizures with etomidate Neurosurg. 2011;25:203–209. anesthesia. Anesth Analg. 1985;64:1226–1227. 9. Jones-Gotman M, Sziklas V, Djordjevic J, et al. Etomidate speech 26. Wagner RL, White PF, Kan PB, et al. Inhibition of adrenal and memory test (eSAM): a new drug and improved intracarotid steroidogenesis by the anesthetic etomidate. N Engl J Med. 1984;31: procedure. Neurology. 2005;65:1723–1729. 415–1421. 10. Baxendale S, Thompson P, Harkness W, et al. Predicting memory 27. Oglesby AJ. Should etomidate be the induction agent of choice for decline following epilepsy surgery: a multivariate approach. rapid sequence intubation in the emergency department? Emerg Med Epilepsia. 2006;47:1887–1894. J. 2004;21:655–659.

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