The Effects of Ketamine on Respiratory Stimulation and Transpulmonary Pressures

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.

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.

Minute ventilation measured during spontaneous breathing trials without ventilator support using a calibrated pneumotachometer connected to the ventilatory circuit. Minute ventilation represents the total volume of air inhaled or exhaled per minute and is calculated as tidal volume multiplied by respiratory rate. Values are reported in liters per minute (L/min). Higher values indicate greater overall ventilation during spontaneous breathing. Measurements were derived from airflow recordings.

Tidal volume measured during spontaneous breathing trials without ventilator support using a calibrated pneumotachometer connected to the ventilatory circuit. Tidal volume represents the volume that enters the lungs during a single breath and is reported in liters (L). Values were derived from airflow recordings analyzed using spirometry software. Higher values indicate larger breath volumes during spontaneous breathing at the predefined study time points.

Inspiratory work of breathing measured during spontaneous breathing trials using esophageal pressure (Pes) and tidal volume recordings. Work of breathing was calculated from the area under the inspiratory limb of the esophageal pressure-volume loop for each breathing cycle. Values were averaged across breaths during the recording period and normalized to tidal volume. Work of breathing was expressed in joules per liter (J/L). Higher values indicate greater mechanical effort required to inhale.

Inspiratory airway resistance measured during spontaneous breathing trials using airway flow and esophageal pressure recordings. Resistance was estimated using the Mead and Whittenberger method, calculated as (Pes - PesLR)/V̇, where Pes is esophageal pressure, PesLR is the pressure on the lung elastic recoil curve at the same tidal volume, and V̇ is airflow. Measurements were made at an absolute tidal volume of 100 ml and averaged across breathing cycles during the recording period. Values are reported in cmH2O/L/s. Higher values indicate greater resistance to airflow during inspiration.

Lung compliance measured during spontaneous breathing trials using tidal volume and esophageal pressure recordings. Compliance was calculated as the change in tidal volume divided by the change in esophageal pressure (ΔVT/ΔPes) measured between zero-flow states at the beginning and end of inspiration. Values represent respiratory system compliance and are reported in milliliters per centimeter of water pressure (mL/cmH2O). Higher values indicate greater lung compliance, reflecting a larger volume change for a given pressure change.