The Effects of Ketamine on Respiratory Stimulation and Transpulmonary Pressures

NCT01969227 | Completed

• 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 (5)

• Change in peak inspiratory flow

  Measured using a pneumotach (Hans Rudolph Inc., Shawnee, KS) connected to the ventilation tubing of the patient during the spontaneous breathing trials.

  Measured 15 minutes prior to initiation of ketamine infusion, at 60 minutes of ketamine infusion at 5mcg/kg/min, at another 60 minutes of infusion at 10mcg/kg/min, and at 2 hours after stopping the infusion

• Change in tidal volume

  Measured using a pneumotach (Hans Rudolph Inc., Shawnee, KS) connected to the ventilation tubing of the patient during the spontaneous breathing trials.

  Measured 15 minutes prior to initiation of ketamine infusion, at 60 minutes of ketamine infusion at 5mcg/kg/min, at another 60 minutes of infusion at 10mcg/kg/min, and at 2 hours after stopping the infusion

• Change in duty cycle

  Measured using a pneumotach (Hans Rudolph Inc., Shawnee, KS) connected to the ventilation tubing of the patient during the spontaneous breathing trials.

  Measured 15 minutes prior to initiation of ketamine infusion, at 60 minutes of ketamine infusion at 5mcg/kg/min, at another 60 minutes of infusion at 10mcg/kg/min, and at 2 hours after stopping the infusion

• Change in respiratory rate

  Measured using a pneumotach (Hans Rudolph Inc., Shawnee, KS) connected to the ventilation tubing of the patient during the spontaneous breathing trials.

  Measured 15 minutes prior to initiation of ketamine infusion, at 60 minutes of ketamine infusion at 5mcg/kg/min, at another 60 minutes of infusion at 10mcg/kg/min, and at 2 hours after stopping the infusion

• Change in minute ventilation

  Measured using a pneumotach (Hans Rudolph Inc., Shawnee, KS) connected to the ventilation tubing of the patient during the spontaneous breathing trials.

  Measured 15 minutes prior to initiation of ketamine infusion, at 60 minutes of ketamine infusion at 5mcg/kg/min, at another 60 minutes of infusion at 10mcg/kg/min, and at 2 hours after stopping the infusion

Secondary Outcomes (9)

• Transpulmonary pressure

  Continuously throughout the study until stopping the ketamine infusion.

• Changes in power spectrum densities

  Continuously throughout the ketamine infusion until 3 hours after stopping the ketamine infusion.

• Oxygen blood saturation

  Continuously throughout the ketamine infusion until 3 hours after stopping the ketamine infusion.

• Changes in volumetric capnography

  Periods of at least five minutes during steady state breathing before and after administration of ketamine.

• Total narcotic consumption

  3 hours after stopping the ketamine infusion

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

Study Officials

• Lorenzo Berra, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Matthias Eikermann, MD, PhD

  Beth Israel Deaconess Medical Center

  STUDY DIRECTOR

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: March 15, 2023

Record last verified: 2023-03

Locations

US (2)