The Effects of Ketamine on Respiratory Stimulation and Transpulmonary Pressures

Maintaining the patency of upper airway in sedated and anesthetized patients is challenging
especially when patients are ready to be weaned from mechanical ventilation. 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. Recent animal
data suggests that when added to propofol in a sedation regimen, ketamine decreased
hypoventilation when compared to propofol alone because ketamine can increase genioglossus
phasic activity while abolishing the coupling between loss of consciousness and upper airway
dilator muscle activity. However, this relationship has not been examined in human in
combination of other drugs.

The purpose of this pharmaco-physiological interaction trial is to evaluate the effects of
ketamine on breathing and electroencephalography in mechanical ventilated patients.
Spirometry will be utilized to evaluate upper airway patency. Polysomnography (PSG- Alice
PDx) will be used to evaluate the effects of ketamine on EEG during wakefulness and sleep.
An esophageal balloon will be inserted to measure esophageal pressure, which enables us to
measure the effects of ketamine on transpulmonary pressure. A volumetric capnography, NICO
noninvasive device from Respironics will be used to measure anatomical dead space, CO2
production, mean expiratory CO2 and slope of the alveolar plateau of the volumetric
capnogram