Hyperventilation Combined With Etomidate or Ketamine Anesthesia in ECT Treatment of Major Depression

Hyperventilation and ECT Seizure Duration: Effects on Cerebral Oxygen Saturation, and Therapeutic Outcome With Comparisons Between Etomidate and Ketamine in Patients With Major Depressive Disorder

This is a randomized controlled study assessing the effect of pre-emptive hyperventilation on ECT seizure duration, cerebral desaturation and remission of depressive symptoms in patients with Major Depressive Disorder. Comparison of etomidate and ketamine on remission of depressive symptoms with and without pre-emptive hyperventilation will also be studied.

Electroconvulsive therapy (ECT) is an effective treatment for medication-resistant forms of depression, including major depressive disorder and mania. Therapeutic success of ECT is related to the duration and quality of Electroencephalogram (EEG) and motor seizures. Previous studies have demonstrated that deliberate hyperventilation augments seizure duration in anesthetized subjects. It has also been shown that seizure activity significantly increases cerebral metabolic rate, predisposing the patient to potentially severe cerebral desaturation events. These desaturation events are predicted to be exacerbated by pre-emptive hyperventilation which has a potent cerebral vasoconstrictive effect. Despite the widespread use of ECT, little is known about the effect of hyperventilation on cerebral metabolism in this setting. Ketamine has recently been demonstrated to have anti-depressant properties in patients with major depressive disorder, suggesting that patients treated with ketamine anesthesia and then ECT, may benefit clinically from the additive effects of both treatment modalities, compared to ECT alone. The investigators hypothesize that hyperventilation will facilitate prolonged seizure duration and faster remission of depressive symptoms. As well there may be significant cerebral desaturation and cardiovascular side effects of ECT therapy following hyperventilation. Lastly, the effect of hyperventilation on the efficacy of ECT therapy may be improved when ketamine anesthesia is used simultaneously. To test this hypothesis this study will compare ketamine anesthesia to etomidate anesthesia. Etomidate is a short acting anesthetic that is commonly used in these procedures. The study objectives (primary and secondary) are as follows: To quantify the effect of hyperventilation and type of anesthetic agent on ECT-induced seizure duration To assess the effect of hyperventilation immediately prior to ECT on cerebral metabolism as measured by cerebral oximetry To determine the effect of hyperventilation and anesthetic agent on the remission of symptoms in Major Depressive Disorder To assess the side effect profile of hyperventilation during ECT on hemodynamics

Major depressive disorder, Etomidate, Ketamine, Hyperventilation, Electroconvulsive therapy, Depression, Anesthesia, Nervous System Diseases, Mental Disorders, Electroencephalography, Cerebral Metabolism

Immediately prior to ECT study patients will be administered intravenous etomidate for anesthesia at a dose of 0.3 mg/kg given as a bolus dose.

Immediately prior to ECT study patients will be administered intravenous ketamine for anesthesia at a dose of 0.5 -1.0 mg/kg given as a bolus dose.

Immediately prior to ECT study patients will be administered intravenous etomidate for anesthesia at a dose of 0.3 mg/kg given as a bolus dose. Hyperventilation will be administered (20 breaths in 30 seconds) by face mask immediately prior to ECT.

Immediately prior to ECT study patients will be administered intravenous ketamine for anesthesia at a dose of 0.5 -1.0 mg/kg given as a bolus dose. Hyperventilation will be administered (20 breaths in 30 seconds) by face mask immediately prior to ECT.

Etomidate will be administered as a bolus intravenously to induce an adequate depth of anesthesia just prior to ECT at a dose of 0.3 mg/kg

Ketamine will be administered as a bolus intravenously to induce an adequate depth of anesthesia just prior to ECT at a dose of 0.5 to 1.0 mg/kg.

Hyperventilation will be performed in patients after full pre-oxygenation and induction of anesthesia, by administering 20 breaths in 30 seconds using a well-fitting face mask immediately before application of the ECT electrical stimulus.

Bilateral, bitemporal electrode placement will be utilized to elicit a seizure via a SpECTrun 5000Q (MECTA Inc.). The electrical dose required will be determined in advance by the patient's attending psychiatrist.

Duration of seizure spike wave morphology will be assessed by the attending psychiatrist and independently by a second psychiatrist.

Duration of motor seizures will be assessed by timing the onset and offset of appropriate motor twitches in the intrinsic foot muscles and extra-ocular muscles by the attending psychiatrist.

Cerebral metabolism will be assessed by continuous cerebral oximetry measurements using the ForeSight Cerebral Oximeter, from immediately prior to ECT to 5 minutes post ECT

Patients will be assessed using a clinician-administered Hamilton Depression Rating Scale (HAM-D) both prior to, and at intervals of 2, 4 and 8 weeks after completion of the study. The HAM-D is a validated healthcare professional-administered assessments of clinical depressive symptoms including: hopelessness, guilt or depressed mood and physical symptoms such as agitation, restlessness and fatigue.

Patients will be assessed using a clinician-administered Montgomery-Asberg Depression Scale (MADRS) both prior to, and at intervals of 2, 4 and 8 weeks after completion of the study. The MADRS is a validated healthcare professional-administered assessments of clinical depressive symptoms including: hopelessness, guilt or depressed mood and physical symptoms such as agitation, restlessness and fatigue.

Systolic, diastolic and mean blood pressure will be recorded every minute from immediately prior to 7 minutes post ECT.

Inclusion Criteria: Adults patients aged 18 to 85 years Diagnosed with Major Depressive Disorder, unipolar or bipolar depression Undergoing ECT for treatment of their symptoms Currently residing in Manitoba Exclusion Criteria: Relative contraindications to ECT therapy (recent MI or CVA, increased intracranial pressure, intracranial mass lesion, intracranial aneurysm, epilepsy, known cardiac arrhythmia, pheochromocytoma, pregnancy) Contraindications to etomidate (sepsis, primary or secondary adrenal insufficiency, porphyria) DSM-V diagnosis of a lifetime history of psychotic spectrum disorder Drug or alcohol dependence, or abuse within the past 3 months, soy-bean oil allergy

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