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

NCT ID: NCT02924090

Last Updated: 2016-10-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2018-12-31

Brief Summary

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.

Detailed Description

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:

1. To quantify the effect of hyperventilation and type of anesthetic agent on ECT-induced seizure duration

2. To assess the effect of hyperventilation immediately prior to ECT on cerebral metabolism as measured by cerebral oximetry

3. To determine the effect of hyperventilation and anesthetic agent on the remission of symptoms in Major Depressive Disorder

4. To assess the side effect profile of hyperventilation during ECT on hemodynamics

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

ECT with Etomidate

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.

Group Type: ACTIVE_COMPARATOR

Etomidate

Intervention Type: DRUG

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

Electroconvulsive therapy (ECT)

Intervention Type: PROCEDURE

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.

ECT with Ketamine

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.

Group Type: ACTIVE_COMPARATOR

Ketamine

Intervention Type: DRUG

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.

Electroconvulsive therapy (ECT)

Intervention Type: PROCEDURE

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.

ECT with Etomidate and Hyperventilation

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.

Group Type: ACTIVE_COMPARATOR

Etomidate

Intervention Type: DRUG

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

Hyperventilation

Intervention Type: PROCEDURE

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.

Electroconvulsive therapy (ECT)

Intervention Type: PROCEDURE

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.

ECT with Ketamine and Hyperventilation

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.

Group Type: ACTIVE_COMPARATOR

Ketamine

Intervention Type: DRUG

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

Intervention Type: PROCEDURE

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.

Electroconvulsive therapy (ECT)

Intervention Type: PROCEDURE

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.

Interventions

Etomidate

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

Intervention Type: DRUG

Ketamine

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.

Intervention Type: DRUG

Hyperventilation

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.

Intervention Type: PROCEDURE

Electroconvulsive therapy (ECT)

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.

Intervention Type: PROCEDURE

Other Intervention Names

Amidate; Ketalar

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Manitoba

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ian McIntyre, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

University of Manitoba

Michael Harrington, MD

Role: PRINCIPAL_INVESTIGATOR

University of Manitoba

Locations

Health Sciences Centre

Winnipeg, Manitoba, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Ian McIntyre, MD, MSc

Role: CONTACT

ian.mcintyre@umanitoba.ca

204 787-1414

Facility Contacts

Ian McIntyre, MD, MSc

Role: primary

ian.mcintyre@umanitoba.ca

204 787-2560

References

Loo C, Simpson B, MacPherson R. Augmentation strategies in electroconvulsive therapy. J ECT. 2010 Sep;26(3):202-7. doi: 10.1097/YCT.0b013e3181e48143.

Reference Type: BACKGROUND

PMID: 20562640 (View on PubMed)

Aksay SS, Bumb JM, Janke C, Hoyer C, Kranaster L, Sartorius A. New evidence for seizure quality improvement by hyperoxia and mild hypocapnia. J ECT. 2014 Dec;30(4):287-91. doi: 10.1097/YCT.0000000000000109.

Reference Type: BACKGROUND

PMID: 24625713 (View on PubMed)

Fabbri F, Henry ME, Renshaw PF, Nadgir S, Ehrenberg BL, Franceschini MA, Fantini S. Bilateral near-infrared monitoring of the cerebral concentration and oxygen-saturation of hemoglobin during right unilateral electro-convulsive therapy. Brain Res. 2003 Dec 5;992(2):193-204. doi: 10.1016/j.brainres.2003.08.034.

Reference Type: BACKGROUND

PMID: 14625058 (View on PubMed)

Ghasemi M, Kazemi MH, Yoosefi A, Ghasemi A, Paragomi P, Amini H, Afzali MH. Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder. Psychiatry Res. 2014 Feb 28;215(2):355-61. doi: 10.1016/j.psychres.2013.12.008. Epub 2013 Dec 13.

Reference Type: BACKGROUND

PMID: 24374115 (View on PubMed)

Other Identifiers

B2015050

Identifier Type: -

Identifier Source: org_study_id