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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01969227
Other study ID # 2013P001690
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date January 2014
Est. completion date December 2022

Study information

Verified date March 2023
Source Massachusetts General Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

Maintaining the patency of the upper airway in sedated and anesthetized patients is challenging especially when patients are ready to be weaned from mechanical ventilation. Spontaneous breathing trial (SBT) is used to expedite the weaning process, which oftentimes requires the reduction and/or discontinuation of sedatives and analgesics. In some surgical patients, reducing these medications can lead to pain associated agitation and inability to conduct SBTs, which may prolong the need for mechanical ventilation. Using medications with narcotic sparing effects and that do not cause respiratory depression may allow for the reduction or discontinuation of agents that depress respiratory drive and subsequently facilitate extubation. Ketamine has been used for many years in critically ill patients for sedation and analgesia. This noncompetitive antagonist of N-methyl-D-aspartate (NMDA) is used as an anesthetic and analgesic and has been shown to reduce opioid consumption and to prevent the development of opioid tolerance. Unlike other anesthetics, ketamine activates respiratory effort and promotes bronchodilation. At subanesthetic plasma concentration, ketamine reduces both opioid and propofol requirements. The goal of this pharmaco-physiological interaction trial is to evaluate the effects of ketamine at a subanesthetic dose on breathing and electroencephalography. The investigators hypothesize that ketamine drip at a subanesthetic infusion rate (low dose ketamine 5 - 10 mcg/kg/min) is associated with respiratory stimulating effects and does not markedly increase transpulmonary pressure in mechanically ventilated patients. The primary outcome is respiratory function, assessed through peak inspiratory flow, tidal volume,respiratory rate, duty cycle, and minute ventilation measured 15 minutes prior to initiation of ketamine infusion (to serve as baseline), at 60 minutes of ketamine infusion at 5mcg/kg/min, at another 60 minutes of infusion at 10mcg/kg/min, at which point the infusion is stopped for 3 hours for a final set of measurements.


Recruitment information / eligibility

Status Completed
Enrollment 15
Est. completion date December 2022
Est. primary completion date December 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - 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 Exclusion Criteria: - Esophageal injury - Allergic to ketamine - Known neurodegenerative disorders - Major neurologic disorders (elevated ICP)

Study Design


Intervention

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

Locations

Country Name City State
United States Beth Israel Deaconess Medical Center Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
Massachusetts General Hospital Beth Israel Deaconess Medical Center

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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 Transpulmonary pressure Standard nutritional nasogastric tube with an integrated esophageal balloon will be inserted if not already in place by a trained physician or respiratory therapist prior to initiation of ketamine drip and will be used for measurement of transpulmonary pressure. for the study period (approximately 5 hours) Continuously throughout the study until stopping the ketamine infusion.
Secondary Changes in power spectrum densities Electroencephalography (EEG)-based power spectrum densities will be measured using the Sedline brain function monitor (Masimo Corporation, Irvine, CA) Continuously throughout the ketamine infusion until 3 hours after stopping the ketamine infusion.
Secondary Oxygen blood saturation Pulse oxymetry Continuously throughout the ketamine infusion until 3 hours after stopping the ketamine infusion.
Secondary Changes in volumetric capnography Measures through volumetric capnography: NICO© device from Respironics (Hartford, CT). Periods of at least five minutes during steady state breathing before and after administration of ketamine.
Secondary Total narcotic consumption Obtained from the medical record and flow sheets. 3 hours after stopping the ketamine infusion
Secondary Number of days mechanically ventilated Difference in days between intubation and extubation. Obtained from the medical record and flow sheets. 3 hours after stopping the ketamine infusion
Secondary Richmond Agitation Sedation Scale (RASS) Obtained from the medical record and flow sheets. 3 hours after stopping the ketamine infusion
Secondary Critical care pain observation tool (CPOT) Obtained from the medical record and flow sheets. 3 hours after stopping the ketamine infusion
Secondary Confusion Assessment Measurement for the ICU (CAM-ICU) Obtained from the medical record and flow sheets. 3 hours after stopping the ketamine infusion
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