the effects of ketamine on respiratory stimulation and transpulmonary pressures

Conditions: Mechanical Ventilation; Airway Patency; Respiratory Depression

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.

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.

Eligibility criteria:
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)

Keywords: subanesthetic ketamine mechanical ventilation transpulmonary pressure spontaneous breathing trial extubation