Effects of ketamine infusion on breathing and encephalography in spontaneously breathing ICU patients

Background: Preclinical studies suggest that ketamine stimulates breathing. We investigated whether adding a ketamine infusion at low and high doses to propofol sedation improves inspiratory flow and enhances sedation in spontaneously breathing critically ill patients. Methods: : In this prospective interventional study, twelve intubated, spontaneously breathing patients received ketamine infusions at 5 mcg/kg/min, followed by 10 mcg/kg/min for 1 hour each. Airway flow, pressure, and esophageal pressure were recorded during a spontaneous breathing trial (SBT) at baseline, and during the SBT conducted at the end of each ketamine infusion regimen. SBT consisted of one-minute breathing with zero end-expiratory pressure and no pressure support. Changes in inspiratory flow at the pre-specified time points were assessed as the primary outcome. Ketamine-induced changes in gamma electroencephalogram power was the key secondary endpoint. We also analyzed changes in other ventilatory parameters respiratory timing, and resistive and elastic inspiratory work of breathing. Results: : Ketamine infusion of 5 and 10 mcg/kg/min increased inspiratory flow (median, IQR) from 0.36 (0.29-0.46) L/s at baseline to 0.47 (0.32-0.57) L/s and 0.44 (0.33-0.58) L/s, respectively (p=0.013). Resistive work of breathing decreased from 0.4 (0.1–0.6) J/l at baseline to 0.2 (0.1–0.3) J/l after ketamine 10 mcg/kg/min (p=0.042), while elastic work of breathing remained unchanged. Electroencephalogram gamma power (19–44 Hz) increased compared to baseline (p<0.01). Conclusions: : In intubated, spontaneously breathing patients receiving low-dose propofol, ketamine increased inspiratory flow, reduced inspiratory work of breathing, and was associated with an “activated” electroencephalographic pattern. These characteristics might facilitate weaning from mechanical ventilation.