Dr. Cumming's research has found no significant cardiovascular side effects in continuous sedation of dexmedetomidine without a loading dose in critically ill children for infusions up to 24 hours.
Research of Brian Cummings, MD
Brian Cummings, MD, Assistant in Pediatrics, MassGeneral Hospital for Children; Instructor in Pediatrics, Harvard Medical School
Cardiovascular safety of dexmedetomidine infusions without a loading dose in the pediatric intensive care unit
Finding the ideal sedation regimen in children undergoing mechanical ventilation is challenging. On the one hand, the less sedation you receive, the less likelihood you are to obtain hospital acquired infections, and the earlier you are likely to be free from mechanical ventilation. At the same time, young children will not tolerate a tube in their throat and will quickly try to remove the offending agent. One of the goals of our work in the Pediatric Intensive Care (PICU) is to find the right balance of sedation with the least amount of side effects.
Under the direction of Natan Noviski in the MGHfC PICU, Allison Cowl and Brian Cummings conducted a prospective study using the drug dexmedetomidine for sedation for mechanically ventilated pediatric critically ill patients.
Dexmedetomidine is being used more often in children due to its minimal effect on respiration, possibly allowing patients to extubate sooner without side effects from typical opiates and benzodiazepines. One of its side effects however is lower heart rates and blood pressure, which has limited its use. Prior adult and pediatric studies have examined heart rate and cardiovascular effects in the setting of a loading dose followed by short term infusions of dexmedetomidine. In recent research we sought to describe these parameters in critically ill children related to continuous infusion of dexmedetomidine without a loading dose for up to 24 hours of infusion to demonstrate its safety in our population.
Hemodynamically stable intubated patients in the pediatric critical care unit were infused at a rate of 0.7mcg/kg/hour of dexmedetomidine for sedation prior to an anticipated extubation attempt within 24 hours. Patients received a minimum of 6 hours of infusion of drug and cardiovascular effects were monitored until infusion discontinuation. EKG was monitored continuously and HR, SBP, DBP, MAP, RR, and O2 sat were recorded at baseline, at 5, 10, 15, 25, 35, 45, 55, and 65 minutes and then hourly thereafter up to 24 hours. Patients were predetermined to exit from study by HR and BP set-points <5% for age. Changes in hemodynamic variables were compared to baseline by paired t-test and repeated measures ANOVA analysis.
A total of 17 intubated patients, mean age of 3 ± 4.6 years, mean weight 20 ± 22.7 kg received a dexmedetomidine infusion for a mean of 16 ± 7.2 hours. There were no conduction abnormalities. 1 patient required discontinuation of infusion for predetermined low HR limits at hour 13 (baseline HR 64, discontinued at HR 57) coinciding with planned extubation. Mean HR decreased by 9 bpm at 65 minutes but HR changes were not statistically significant at any frame. 35% of patients had a decline in heart rate >15% from baseline at 6 hours (similar frequency at 8 and 12 hours) without clinical intervention required. See Figure 1. Similarly, there was no significant change in SBP, MAP and DBP during the observed time periods.
We have found no significant cardiovascular side effects in continuous sedation of dexmedetomidine without a loading dose in critically ill children for infusions up to 24 hours. Withholding dexmedetomidine loading dose may result in more patient tolerability and provider comfort with managing infusions in the pediatric intensive care unit. Based on this reassuring research, we currently routinely use sedation infusions even longer then 24 hours when indicated for children, and will further characterize this safety in future work.
Figure 1. Heart rate values during continuous infusion of dexmedetomidine over time. Boxes represent interquartile range with median, circles represent mean, and whickers represent minimum and maximum values.