Measured using a pneumotach (Hans Rudolph Inc., Shawnee, KS) connected to the ventilation tubing of the patient during the spontaneous breathing trials.
The Effects of Ketamine on Respiratory Stimulation and Transpulmonary Pressures
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.
Intervention / Treatment
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Subanesthetic ketamine (DRUG)Ketamine drip at a subanesthetic infusion rate (low dose ketamine 5 - 10 mcg/kg/min)
Condition or Disease
- Mechanical Ventilation
- Airway Patency
- Respiratory Depression
Phase
Study Design
| Study type: | INTERVENTIONAL |
|---|---|
| Status: | Completed |
| Study results: | No Results Available |
| Age: | 18 Years and older (Adult, Older Adult) |
| Enrollment: | 15 (ACTUAL) |
| Funded by: | Other |
| Allocation: | N/A |
| Primary Purpose: | Treatment |
Masking |
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Clinical Trial Dates
| Start date: | Jan 01, 2014 | |
|---|---|---|
| Primary Completion: | Dec 01, 2022 | ACTUAL |
| Completion Date: | Dec 01, 2022 | ACTUAL |
| Study First Posted: | Oct 25, 2013 | ESTIMATED |
| Results First Posted: | Aug 31, 2020 | |
| Last Updated: | Mar 13, 2023 |
Sponsors / Collaborators
Lead Sponsor:
Massachusetts General Hospital
Responsible Party:
N/A
Location
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.
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.
Participant Groups
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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.
Eligibility Criteria
| Sex: | All |
|---|---|
| Minimum Age: | 18 |
| Age Groups: | Adult / Older Adult |
| Healthy Volunteers: | Yes |
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)
* 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)
Primary Outcomes
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Measured using a pneumotach (Hans Rudolph Inc., Shawnee, KS) connected to the ventilation tubing of the patient during the spontaneous breathing trials.
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Measured using a pneumotach (Hans Rudolph Inc., Shawnee, KS) connected to the ventilation tubing of the patient during the spontaneous breathing trials.
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Measured using a pneumotach (Hans Rudolph Inc., Shawnee, KS) connected to the ventilation tubing of the patient during the spontaneous breathing trials.
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Measured using a pneumotach (Hans Rudolph Inc., Shawnee, KS) connected to the ventilation tubing of the patient during the spontaneous breathing trials.
Secondary Outcomes
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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)
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Electroencephalography (EEG)-based power spectrum densities will be measured using the Sedline brain function monitor (Masimo Corporation, Irvine, CA)
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Pulse oxymetry
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Measures through volumetric capnography: NICO© device from Respironics (Hartford, CT).
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Obtained from the medical record and flow sheets.
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Difference in days between intubation and extubation. Obtained from the medical record and flow sheets.
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Obtained from the medical record and flow sheets.
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Obtained from the medical record and flow sheets.
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Obtained from the medical record and flow sheets.
More Details
| NCT Number: | NCT01969227 |
|---|---|
| Other IDs: | 2013P001690 |
| Study URL: | https://clinicaltrials.gov/study/NCT01969227 |
Last updated: Sep 29, 2023