Effects of Ketamine Infusion on Breathing and Encephalography in Spontaneously Breathing ICU Patients

Abstract

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 h 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 change in beta-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 = .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 = .042), while elastic work of breathing remained unchanged. Electroencephalogram beta-gamma power (19-44 Hz) increased compared to baseline ( p < .01). Conclusions In intubated, spontaneously breathing patients receiving a constant rate of 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.

Continuous infusion ketamine for sedation of mechanically ventilated adults in the intensive care unit: A scoping review

“…Of the 27 articles relating to the use of continuous ketamine infusions for sedation or analgesia during MV, there were nine prospective randomised studies [29][30][31][32][33][34][35][36][37] , one prospective cohort study, 38 , 11 retrospective cohort [39][40][41][42][43][44] or observational studies, [45][46][47][48][49] and six case reports or case series (Figure 2). [50][51][52][53][54][55] A total of 987 participants received continuous ketamine infusions whilst undergoing MV.…”

“…Mechanically ventilated patients were included from the following ICUs: Medical ICU (40.7%), 36,41,45,47,50,54,55 Mixed, general, or unspecified ICU (39.0%), 29,34,39,43,44,46,48,53 Neurosurgical ICU (8.2%), 30,37,49,51 Cardiac ICU (6.7%), 31,33 Surgical ICU (2.8%), 32,38,40 Obstetric ICU, 35 and Trauma ICU (2.6%). 42,52 The most frequent country of origin was the USA (55.5%), other countries included France, Germany, India, and Saudi Arabia, with only one case report coming from the United Kingdom.…”

“…49 Duration of continuous ketamine infusions also varied significantly across studies (Table 1), with some study designs stipulating a maximum duration, and others continuing until cessation of MV (or death of patient). The minimum reported duration was 2h 38 and the maximum was 36 days (864 h). 49 Six studies reported durations of infusions under 24 h, nine reported durations between 24 and 72 h, and ten studies reported durations over 72 h.…”

“…Whilst Bourgoin et al 30 reported no significant difference in MAP, they found significantly less fluid was administered in the ketamine group (429 ± 405ml vs 992 ± 703ml; p = 0.02). 38 demonstrated improved respiratory dynamics including inspiratory airflow, increased minute ventilation, and tidal volumes, as well as improved work of breathing. Achar et al 50 reported improved gas exchange and bronchodilation following the addition of ketamine for refractory asthma.…”

“…33,34,40,42,[46][47][48] Other primary outcomes included sedation efficacy, 32,35,41,53 safety of ketamine infusions, 44,49 effects on neurological parameters e.g. intra-cerebral pressure, 30,37 cardiovascular effects for example, blood pressure and vasopressor requirements, 31,36,39,47 respiratory parameters for example, gas exchange and airway pressures, 38,50 feasibility data, 29 and effect on delirium. 43 Commonly reported secondary outcomes included cardiovascular parameters, vasopressor requirements, ICU length of stay, ventilator free days/ duration of MV, adverse events, and mortality.…”