The Effects of Ketamine on Respiratory Stimulation and Transpulmonary Pressures

NCT01969227 | Completed Results

• 1 other identifier: 2013P001690
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

Impairment of airway patency is a common cause of extubation failure and opioids and hypnotics can adversely affect airway patency. Ketamine, a noncompetitive antagonist of N-methyl-D-aspartate (NMDA), unlike other anesthetics activates respiratory effort and promotes bronchodilation. At subanesthetic plasma concentration, ketamine reduces both opioid and propofol requirements. The purpose of this pharmaco-physiological interaction trial is to evaluate the effects of ketamine on breathing and electroencephalography in mechanically ventilated patients.

Conditions

Mechanical Ventilation; Airway Patency; Respiratory Depression

Keywords

Subanesthetic ketamine; Mechanical ventilation; Transpulmonary pressure; Spontaneous breathing trial; Extubation

Outcome Measures

Primary Outcomes (1)

• Inspiratory Airflow

  Inspiratory airflow measured during spontaneous breathing trials without ventilator support using a calibrated pneumotachometer connected to the ventilatory circuit. Airflow signals were recorded along with airway and esophageal pressures and analyzed. Inspiratory airflow represents the rate of air entering the lungs during inspiration and is reported in liters per second (L/s). Higher values indicate greater inspiratory airflow during spontaneous breathing. Measurements were obtained during brief spontaneous breathing trials performed at predefined study time points.

  During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min

Secondary Outcomes (6)

• EEG Beta-gamma Power

  Baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.

• Minute Ventilation

  During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.

• Tidal Volume

  During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.

• Work of Breathing

  During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.

• Inspiratory Airway Resistance

  During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.

Study Arms (1)

Cohort

EXPERIMENTAL

Adult mechanically ventilated patients who are deemed eligible for a spontaneous breathing trial and are candidates to receive subanesthetic ketamine by the primary critical care team.

Drug: Subanesthetic ketamine

Interventions

Subanesthetic ketamine DRUG

Ketamine drip at a subanesthetic infusion rate (low dose ketamine 5 - 10 mcg/kg/min)

Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years admitted to ICU requiring mechanical ventilation
• Suitable for spontaneous breathing trial
• Candidate to received low dose ketamine by the primary critical care team

You may not qualify if:

• Esophageal injury
• Allergic to ketamine
• Known neurodegenerative disorders
• Major neurologic disorders (elevated ICP)

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Beth Israel Deaconess Medical Center: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (6)

• Eikermann M, Grosse-Sundrup M, Zaremba S, Henry ME, Bittner EA, Hoffmann U, Chamberlin NL. Ketamine activates breathing and abolishes the coupling between loss of consciousness and upper airway dilator muscle dysfunction. Anesthesiology. 2012 Jan;116(1):35-46. doi: 10.1097/ALN.0b013e31823d010a.

  PMID: 22108392 BACKGROUND

• Esteban A, Frutos F, Tobin MJ, Alia I, Solsona JF, Valverdu I, Fernandez R, de la Cal MA, Benito S, Tomas R, et al. A comparison of four methods of weaning patients from mechanical ventilation. Spanish Lung Failure Collaborative Group. N Engl J Med. 1995 Feb 9;332(6):345-50. doi: 10.1056/NEJM199502093320601.

  PMID: 7823995 BACKGROUND

• Menigaux C, Fletcher D, Dupont X, Guignard B, Guirimand F, Chauvin M. The benefits of intraoperative small-dose ketamine on postoperative pain after anterior cruciate ligament repair. Anesth Analg. 2000 Jan;90(1):129-35. doi: 10.1097/00000539-200001000-00029.

  PMID: 10624993 BACKGROUND

• Hirota K, Hashimoto Y, Sakai T, Sato T, Ishihara H, Matsuki A. In vivo spasmolytic effect of ketamine and adrenaline on histamine-induced airway constriction. Direct visualization method with a superfine fibreoptic bronchoscope. Acta Anaesthesiol Scand. 1998 Feb;42(2):184-8. doi: 10.1111/j.1399-6576.1998.tb05106.x.

  PMID: 9509200 BACKGROUND

• Morel DR, Forster A, Gemperle M. Noninvasive evaluation of breathing pattern and thoraco-abdominal motion following the infusion of ketamine or droperidol in humans. Anesthesiology. 1986 Oct;65(4):392-8. doi: 10.1097/00000542-198610000-00008.

  PMID: 3767037 BACKGROUND

• Kissin I, Bright CA, Bradley EL Jr. The effect of ketamine on opioid-induced acute tolerance: can it explain reduction of opioid consumption with ketamine-opioid analgesic combinations? Anesth Analg. 2000 Dec;91(6):1483-8. doi: 10.1097/00000539-200012000-00035.

  PMID: 11094005 BACKGROUND

MeSH Terms

Conditions

Respiratory Insufficiency

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Results Point of Contact

• Title: Lorenzo Berra, MD
• Organization: Massachusetts General Hospital

lberra@mgh.harvard.edu

617-726-3030

Study Officials

• Lorenzo Berra, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Matthias Eikermann, MD, PhD

  Beth Israel Deaconess Medical Center

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Respiratory Care

Study Record Dates

• First Submitted: October 8, 2013
• First Posted: October 25, 2013
• Study Start: January 1, 2014
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: May 19, 2026
• Results First Posted: May 19, 2026

Record last verified: 2026-04

Locations

US (2)