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A dose-response study of dexmedetomidine administered as the primary sedative in infants following open heart surgery
Felice Su1, Susan C Nicolson, Athena F Zuppa
1Department of Pediatrics, Stanford University, Palo Alto, CA, USA. felicesu@stanford.edu
Insights
Dexmedetomidine effectively sedated infants after heart surgery, reducing the need for other medications and enabling successful extubation. Hemodynamic changes were minimal and not clinically significant.
Area of Science:
- Pediatric critical care medicine
- Pharmacology
- Cardiovascular surgery
Background:
- Infants undergoing open-heart surgery often require mechanical ventilation and sedation.
- Optimizing sedation and analgesia is crucial for patient recovery and extubation success.
- Dexmedetomidine is an alpha-2 adrenergic agonist used for sedation, but its dose-response in this specific population requires further elucidation.
Purpose of the Study:
- To determine the dose-response relationship of dexmedetomidine in sedating infants post-open-heart surgery.
- To evaluate the impact of varying dexmedetomidine doses on sedation levels, supplemental medication use, and extubation outcomes.
- To assess the pharmacokinetic-pharmacodynamic effects of dexmedetomidine in this vulnerable patient group.
Main Methods:
- A prospective, open-label, dose-escalation study was conducted in a tertiary pediatric cardiac intensive care unit.
- Thirty-six infants (1-24 months) received escalating doses of intravenous dexmedetomidine (loading doses: 0.35, 0.7, 1 mcg/kg; continuous infusions: 0.25, 0.5, 0.75 mcg/kg/hr).
- Pharmacodynamic endpoints included sedation scores, supplemental medication use, time to extubation, respiratory function, and hemodynamic parameters.
Main Results:
- Infants receiving dexmedetomidine achieved deeper sedation (University of Michigan Sedation Scale 2.6 vs. 1) with significantly less supplemental sedation and analgesia.
- Thirty-one out of thirty-six infants were successfully extubated while on dexmedetomidine infusion; only one patient required prolonged intubation due to oversedation.
- A transient decrease in heart rate was observed during dexmedetomidine infusion compared to baseline (132 vs. 161 bpm), but it was not clinically significant and heart rate increased post-infusion (132 vs. 128 bpm). No significant changes in mean arterial blood pressure were noted.
Conclusions:
- Dexmedetomidine administration provides effective sedation in infants following open-heart surgery, reducing the need for additional sedatives and analgesics.
- The use of dexmedetomidine facilitates successful tracheal extubation in this population while on continuous infusion.
- While dexmedetomidine may transiently decrease heart rate postoperatively, these changes are not clinically significant and do not impede recovery.
Objective:
To evaluate the dose-response relationship of dexmedetomidine in infants with congenital heart disease postoperative from open heart surgery.
Design:
Prospective open-label dose-escalation pharmacokinetic-pharmacodynamic study.
Setting:
Tertiary pediatric cardiac ICU.
Patients:
Thirty-six evaluable infants, 1-24 months old, postoperative from open heart surgery requiring mechanical ventilation.
Interventions:
Cohorts of 12 infants were enrolled sequentially to one of the three IV loading doses of dexmedetomidine (0.35, 0.7, and 1 mcg/kg) over 10 minutes followed by respective continuous infusions (0.25, 0.5, and 0.75 mcg/kg/hr) for up to 24 hours.
Measurements And Main Results:
Dexmedetomidine plasma concentrations were obtained at timed intervals during and following discontinuation of infusion. Pharmacodynamic variables evaluated included sedation scores, supplemental sedation and analgesia medication administration, time to tracheal extubation, respiratory function, and hemodynamic parameters. Infants achieved a deeper sedation measured by the University of Michigan Sedation Scale score (2.6 vs 1) despite requiring minimal supplemental sedation (0 unit doses/hr) and fewer analgesic medications (0.07 vs 0.15 unit doses/hr) while receiving dexmedetomidine compared with the 12-hour follow-up period. Thirty-one patients were successfully extubated while receiving the dexmedetomidine infusion. Only one patient remained intubated due to oversedation during the infusion. While receiving dexmedetomidine, there was a decrease in heart rate compared with baseline, 132 versus 161 bpm, but there was an increase in heart rate compared with postinfusion values, 132 versus 128 bpm. There was no statistically or clinically significant change in mean arterial blood pressure.
Conclusions:
Dexmedetomidine administration in infants following open heart surgery can provide improved sedation with reduction in supplemental medication requirements, leading to successful extubation while receiving a continuous infusion. The postoperative hemodynamic changes that occur in infants postoperative from open heart surgery are multifactorial. Although dexmedetomidine may play a role in decreasing heart rate immediately postoperative, the changes were not clinically significant and did not fall below postinfusion heart rates.
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