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

Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02924090
• Other study ID #: B2015050
• Status: Recruiting
• Phase: Phase 4
• First received: September 30, 2016
• Last updated: October 20, 2016
• Start date: September 2016
• Est. completion date: December 2018

Study information

• Verified date: September 2016
• Source: University of Manitoba
• Contact: Ian McIntyre, MD, MSc
• Phone: 204 787-1414
• Email: ian.mcintyre[@]umanitoba.ca
• Is FDA regulated: No
• Health authority: Canada: Health CanadaCanada: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: December 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Hyperventilation

Intervention

Drug:
• 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
• 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.

Procedure:
• 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.
• 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.

Locations

Country	Name	City	State
Canada	Health Sciences Centre	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
University of Manitoba

Country where clinical trial is conducted

Canada, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	EEG seizure duration (seconds)	Duration of seizure spike wave morphology will be assessed by the attending psychiatrist and independently by a second psychiatrist.	Up to 3 minutes post ECT	No
Primary	ECT-induced seizure duration (seconds)	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.	Up to 3 minutes post ECT	No
Secondary	Changes in cerebral metabolism assessed by cerebral saturation (%)	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	Up to 5 minutes post ECT	No
Secondary	Remission of depressive symptoms assessed by HAM-D	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.	Approximately one week prior to, and at 2, 4 and 8 weeks post ECT	No
Secondary	Remission of depressive symptoms assessed by MADRS	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.	Approximately one week prior to, and at 2, 4 and 8 weeks post ECT	No
Secondary	Effect on blood pressure	Systolic, diastolic and mean blood pressure will be recorded every minute from immediately prior to 7 minutes post ECT.	Up to 7 minutes post ECT	No
Secondary	Effect on heart rate	Heart rate (bpm) will be continuously recorded from immediately prior to 7 minutes post ECT.	Up to 7 minutes post ECT	No
Secondary	Duration of stay in post-anesthesia care unit (hours)		Up to 2 hours post arrival in post-anesthesia care unit (PACU).	No
Secondary	Incidence of nausea in post-anesthesia care unit (%)	The number of instances of nausea while in PACU will be recorded.	Up to 2 hours post arrival in PACU.	No
Secondary	Incidence of vomiting in post-anesthesia care unit (%)	The number of instances of vomiting while in PACU will be recorded.	Up to 2 hours post arrival in PACU.	No