Trial Outcomes & Findings for The Effects of Ketamine on Respiratory Stimulation and Transpulmonary Pressures (NCT NCT01969227)

NCT ID: NCT01969227

Last Updated: 2026-05-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

15 participants

Primary outcome timeframe

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

Results posted on

2026-05-19

Participant Flow

Participants were recruited in the surgical ICUs of two Boston academic medical centers (Massachusetts General Hospital and Beth Israel Deaconess Medical Center). Study personnel screened ICU censuses daily (7:30am-10:00pm) and through clinician referral. Eligible intubated adults suitable for SBT and on stable sedation ≥3 hours were approached via a clinician, with surrogate written consent obtained.

No specific pre-assignment run-in or washout period occurred. After enrollment and confirmation of eligibility, participants proceeded directly to the study intervention and measurements according to the protocol.

Participant milestones

Participant milestones
Measure	Ketamine Infusion (5 Then 10 mcg/kg/Min) During Propofol Sedation Participants received a continuous infusion of ketamine at 5 mcg/kg/min for 1 hour followed by 10 mcg/kg/min for another hour while maintained on a constant propofol sedation rate. Spontaneous breathing trials (SBT) with zero end-expiratory pressure and no pressure support were performed for 1 minute at baseline (before ketamine), after 1 hour of low-dose ketamine, and after 1 hour of high-dose ketamine. During these trials, inspiratory flow, tidal volume, minute ventilation, respiratory rate, esophageal pressure, and work of breathing were measured. Continuous EEG monitoring was performed throughout the study period. After 2 hours, ketamine infusion was discontinued and routine ICU care continued.
Overall Study STARTED	15
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Ketamine Infusion (5 Then 10 mcg/kg/Min) During Propofol Sedation Participants received a continuous infusion of ketamine at 5 mcg/kg/min for 1 hour followed by 10 mcg/kg/min for another hour while maintained on a constant propofol sedation rate. Spontaneous breathing trials (SBT) with zero end-expiratory pressure and no pressure support were performed for 1 minute at baseline (before ketamine), after 1 hour of low-dose ketamine, and after 1 hour of high-dose ketamine. During these trials, inspiratory flow, tidal volume, minute ventilation, respiratory rate, esophageal pressure, and work of breathing were measured. Continuous EEG monitoring was performed throughout the study period. After 2 hours, ketamine infusion was discontinued and routine ICU care continued.
Overall Study ICU intervention (fentanyl bolus causing apnea)	1
Overall Study ICU interventions limiting data acquisition	2

Baseline Characteristics

Sex was reported for all participants included in the analysis population. No participants were excluded from this baseline measure.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ketamine Infusion (5 Then 10 mcg/kg/Min) During Propofol Sedation n=12 Participants Participants received a continuous ketamine infusion of 5 mcg/kg/min for 1 hour followed by 10 mcg/kg/min for another hour while maintained on a constant propofol sedation infusion. Spontaneous breathing trials with PEEP 0 and no pressure support were performed at baseline, after 1 hour of low-dose ketamine, and after 1 hour of high-dose ketamine. Respiratory variables, work of breathing, esophageal pressure, and EEG activity were recorded during these trials.
RASS (Richmond Agitation-Sedation Scale) at study start	-1 score n=12 Participants
Primary ICU admission diagnosis / reason for mechanical ventilation Respiratory	4 Participants n=12 Participants
Age, Continuous	62 years STANDARD_DEVIATION 20 • n=12 Participants
Sex: Female, Male Female	7 Participants n=12 Participants • Sex was reported for all participants included in the analysis population. No participants were excluded from this baseline measure.
Sex: Female, Male Male	5 Participants n=12 Participants • Sex was reported for all participants included in the analysis population. No participants were excluded from this baseline measure.
Body Mass Index (BMI)	26 kg/m^2 n=12 Participants • BMI was reported for all participants included in the analysis population. No participants were excluded from this baseline measure analysis.
APACHE II (Acute Physiology and Chronic Health Evaluation II) score	15 points n=12 Participants • APACHE II was reported for all participants included in the analysis population. No participants were excluded from this baseline measure analysis.
SOFA (Sequential Organ Failure Assessment) score	5 points n=12 Participants
Primary ICU admission diagnosis / reason for mechanical ventilation Trauma	3 Participants n=12 Participants
Primary ICU admission diagnosis / reason for mechanical ventilation Infection	3 Participants n=12 Participants
Primary ICU admission diagnosis / reason for mechanical ventilation Cardiovascular	1 Participants n=12 Participants
Primary ICU admission diagnosis / reason for mechanical ventilation Postoperative	1 Participants n=12 Participants
History of pulmonary disease	6 Participants n=12 Participants

PRIMARY outcome

Timeframe: 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

Population: The analysis population included the 12 participants who completed the study measurements. Three enrolled participants were excluded from analysis because study measurements could not be completed due to clinical events during the study period.

Outcome measures

Outcome measures
Measure	Ketamine Infusion (5 Then 10 mcg/kg/Min) During Propofol Sedation n=12 Participants Participants received a continuous infusion of ketamine at 5 mcg/kg/min for 1 hour followed by 10 mcg/kg/min for another hour while maintained on a constant propofol sedation rate. Spontaneous breathing trials (SBT) with zero end-expiratory pressure and no pressure support were performed for 1 minute at baseline (before ketamine), after 1 hour of low-dose ketamine, and after 1 hour of high-dose ketamine. During these trials, inspiratory flow, tidal volume, minute ventilation, respiratory rate, esophageal pressure, and work of breathing were measured. Continuous EEG monitoring was performed throughout the study period. After 2 hours, ketamine infusion was discontinued and routine ICU care continued.
Inspiratory Airflow After 60 min ketamine 10 mcg/kg/min	0.44 L/s Interval 0.33 to 0.58
Inspiratory Airflow Baseline (before ketamine infusion)	0.36 L/s Interval 0.29 to 0.46
Inspiratory Airflow After 60 min ketamine 5 mcg/kg/min	0.47 L/s Interval 0.32 to 0.57

SECONDARY outcome

Timeframe: 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.

Population: The analysis population included the 12 participants who completed the study measurements and had analyzable EEG recordings.

Electroencephalogram (EEG) power spectrum density was measured using four frontal electrodes with the SedLine monitor and analyzed using multitaper spectral methods. Changes in beta-gamma power (19-44 Hz) were expressed in decibels (dB) relative to baseline using artifact-free \~3-minute segments at predefined time points. The reported value represents the maximum increase in spectral power across the frequency range, capturing the strongest frequency-specific effect, which may be diluted by averaging across the band if central tendency is used. This approach is standard in spectral analyses to detect peak effects and potential frequency shifts. Power spectra are continuous functions and peak values are the dominant signal components because they represent the strongest oscillatory activity the brain could achieve in a predefined frequency range.