Association between Simulated Ketamine Exposures and Oxygen Saturations in Children

Figures & data

Table 1. Extracted clinical data of children exposed to ketamine.

Clinical data extracted	n = 2022
Postnatal age (years)	3.1 (0.8–8.9)
Weight (kg)	14 (8–28)
Female sex	904 (45%)
Supported with ECMO	25 (1%)
Ketamine dosing (mg/kg)	1 (0.5–1.12)
Number of doses per subject	2 (1–3)
Simulated plasma concentration (ng/ml)	218.2 (69.3–682.3)
Simulated cumulative plasma AUC (ng*h/ml)	1800 (1000–3300)
Baseline oxygen saturation	98 (89–100)
Baseline respiratory support:   None/room air   Nasal cannula, face mask, tent or oxyhood   High-flow nasal cannula   Other noninvasive ventilation   Invasive mechanical ventilation	1859 (92%) 38 (2%) 10 (<1%) 37 (2%) 78 (4%)
Saturation shift from normal baseline:   Remain normal   To mild desaturation   To significant desaturation	1221 (61%) 53 (3%) 139 (7%)

Data shown are median (range) or counts (%).

AUC: Area under the curve; ECMO: Extracorporeal membrane oxygenation.

Figure 1. Relationship between simulated plasma ketamine exposure and oxygen saturation.

Relationship between simulated plasma ketamine exposure and oxygen saturation according to: (A) all simulated ketamine concentrations versus concomitant oxygen saturation; (B) maximum plasma concentration of ketamine per subject versus concomitant oxygen saturation; (C) all simulated ketamine concentrations versus concomitant absolute change in oxygen saturation from baseline; and (D) cumulative area under the ketamine concentration-time profile versus concomitant oxygen saturation. Oxygen saturation cutoff values of 92, 88 and 85% are depicted with horizontal red dashed lines. Ketamine plasma concentrations cutoffs previously associated with efficacy are shown with horizontal grey dashed lines.

Figure 2. Relationship between simulated ketamine exposure and systemic oxygen saturations by postnatal age.

Relationship between simulated ketamine exposure and systemic oxygen saturations by postnatal age according to: (A) ≤1 month of age; (B) >1 month to 2 years of age; (C) >2 years to 6 years of age; (D) >6 years to 12 years of age; and (E) >12 years of age. Oxygen saturation cutoff values of 92, 88 and 85% are depicted with horizontal red dashed lines. Ketamine plasma concentrations cutoffs previously associated with efficacy are shown with vertical grey dashed lines.

Figure 3. Relationship between simulated ketamine exposure and systemic oxygen saturations stratified by time after first dose.

Relationship between simulated ketamine exposure and systemic oxygen saturations stratified by time after first dose according to: (A) ≤5 min after first dose; (B) >5–15 min after first dose; (C) >15–30 min after first dose; (D) >30–60 min after first dose; and (E) >60 min after first dose. Oxygen saturation cutoff values of 92, 88 and 85% are depicted with horizontal red dashed lines. Ketamine plasma concentrations cutoffs previously associated with efficacy are shown with vertical grey dashed lines.

Table 2. Adjusted association between the highest simulated plasma ketamine concentration or the simulated cumulative area under the concentration versus time curve and drop in oxygen saturation from normal at baseline to <85% during the observational period, controlling for postnatal age and baseline level of respiratory support.

Ketamine exposures	OR (95% CI)
Maximum plasma ketamine concentration (ng/ml)	1.00 (0.99–1.01)
Cumulative AUC over the study period (ng*h/ml)	1.07 (1.02–1.12)

AUC: Area under curve; OR: Odds ratio.