Acute Effects of Ketamine on Intracranial Pressure in Children With Severe Traumatic Brain Injury

Abstract

Objectives: The acute cerebral physiologic effects of ketamine in children have been incompletely described. We assessed the acute effects of ketamine on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in children with severe traumatic brain injury (TBI).

Design: In this retrospective observational study, patients received bolus doses of ketamine for sedation or as a treatment for ICP crisis (ICP > 20 mm Hg for > 5 min). Administration times were synchronized with ICP and CPP recordings at 1-minute intervals logged in an automated database within the electronic health record. ICP and CPP were each averaged in epochs following drug administration and compared with baseline values. Age-based CPP thresholds were subtracted from CPP recordings and compared with baseline values. Trends in ICP and CPP over time were assessed using generalized least squares regression.

Setting: A 30-bed tertiary care children's hospital PICU.

Patients: Children with severe TBI who underwent ICP monitoring.

Interventions: None.

Measurements and main results: We analyzed data from 33 patients, ages 1 month to 16 years, 22 of whom received bolus doses of ketamine, with 127 doses analyzed. Demographics, patient, and injury characteristics were similar between patients who did versus did not receive ketamine boluses. In analysis of the subset of ketamine doses used only for sedation, there was no significant difference in ICP or CPP from baseline. Eighteen ketamine doses were given during ICP crises in 11 patients. ICP decreased following these doses and threshold-subtracted CPP rose.

Conclusions: In this retrospective, exploratory study, ICP did not increase following ketamine administration. In the setting of a guidelines-based protocol, ketamine was associated with a reduction in ICP during ICP crises. If these findings are reproduced in a larger study, ketamine may warrant consideration as a treatment for intracranial hypertension in children with severe TBI.

Figure 1.. ICP and CPP before and after non-ICP-targeted ketamine administration.

For each ketamine administration, mean ICP (Figure A) and CPP (Figure B) were calculated for each epoch. Median values for all administrations are shown. Error bars denote interquartile ranges. No values were significantly different from baseline (−5 to −1 minute before ketamine doses) by multiple t tests with the Bonferroni correction.

Figure 2.. ICP and CPP before and after ICP-targeted ketamine administration.

ICP-targeted ketamine administrations were identified as those preceded by ICP > 20 mmHg for ≥ 5 minutes. For each ketamine administration, mean ICP and CPP were calculated for each epoch. Figures A and B display restricted cubic splines modeling ICP and CPP, respectively. Dotted lines indicate 95% confidence intervals. Asterisks denote significant trends over time by generalized least squares analysis ‘NS’ denotes ‘not significant.’ A shows ICP, and B shows the difference between CPP and age-based CPP threshold. Figures C and D show ICP and CPP, respectively, for individual epochs. Median values are displayed. Error bars denote interquartile range. Asterisks denote values significantly different from baseline (−5 to −1 minute before ketamine doses) by multiple t tests with the Bonferroni correction.

Figure 3.. ICP Difference between baseline and 5 minutes.

Change in ICP from baseline to 5 minutes after ICP-targeted ketamine doses are displayed in a Tukey box-and-whiskers plot. Data are censored, excluding all measurements taken after any additional ICP-targeted medication. The box represents the 25^th and 75^th percentiles, with the median denoted by the horizontal line. Error bars denote the minimum and maximum values lying within 1.5 times the interquartile range, and dots represent values lying outside that range. Mean difference is indicated by “+.” The asterisk indicates that the mean is significantly different from zero (p < 0.05).

Figure 4.. Examples of ICP-targeted drug administration.

ICP (mmHg) is displayed in one-minute intervals for two example patients. Medication administrations are denoted by symbols depicted in the keys below each graph. Figure A shows an ICP crisis treated with ketamine and hypertonic saline prior to resolution of intracranial hypertension. ICP rose again 110 minutes following resolution of the initial crisis. Figure B shows a period with prolonged intracranial hypertension in a patient who received multiple ICP-targeted drugs, including ketamine.