Long-term Dexmedetomidine in Critically Ill Children
The study was approved by the Institutional Review Board of Seattle Children's Hospital, which waived the need for informed consent. We performed a retrospective, observational study of patients in the PICU, cardiac ICU, and neonatal ICU at Seattle Children's between December 1, 2008, and December 1, 2010. Unit protocols at the time of this study included starting dose of 0.2 μg/kg/hr, max dose of 0.7 μg/kg/hr, and use for up to 48 hours unless approved by the unit medical director for longer duration.
We included all patients less than 21 years old who had received a continuous infusion of dexmedetomidine longer than 72 hours. Exclusion criteria include greater than or equal to21 years, inability to obtain clinical information, or discontinuation of dexmedetomidine for any length of time during the first 72 hours. Patients were identified using our information technology database, discern analysis, that enabled us to identify patients with pharmacy charges for dexmedetomidine use longer than 72 hours.
Each patient's record was searched for major diagnosis and surgical procedures. Indication for starting dexmedetomidine, initiation and discontinuation times, initial and maximum dose, duration of use, and the utilization of dexmedetomidine wean were recorded. Blood pressure and heart rate (HR) were recorded for each patient at initiation (considered baseline), 30 minutes and 1, 2, and 72 hours of use, as well as at discontinuation, 30 minutes and 1, 2, 4, 24, and 48 hours after discontinuation. These intervals were chosen given the mean distribution half-life of approximately 10 minutes, duration of action of 4 hours, and the terminal elimination half-life of 2.7 hours.
Given recent work in our institution on sedation protocols by Deeter et al, we used our established Seattle PICU Comfort Score to assess depth of sedation (Table 1). This sedation protocol was used in both the PICU and the cardiac ICU (CICU), whereas the newborn ICU (NICU) had an adjusted regimen. The typical progression of sedation in the PICU and CICU was opioid infusion and as needed intermittent benzodiazepine dosing. If increased sedation was needed, our sedation protocol instructed the addition of a benzodiazepine infusion. After this addition, it was physician preference whether to add a dexmedetomidine infusion or to increase both opioid and benzodiazepine infusion doses. The NICU protocol was similar with the exception that benzodiazepine infusions were not recommended.
Dexmedetomidine infusions were noted to either be weaned off or stopped abruptly. There was not a dexmedetomidine unit protocol or common practice at the time of this study. In regards to opioid and benzodiazepine weaning, it was unit practice to stop the infusions abruptly if on for less than 5 days or wean daily by 20% of the maximum daily dose every day if on for 5–10 days. For those on for greater than 10 days, the opioid and benzodiazepine infusions were typically weaned by 10% on alternating days. However, there was variability based on provider preference and patient tolerance of wean. There was no protocol in place directing which agent should be weaned or discontinued first. However, dexmedetomidine was typically discontinued first, but there was variability among providers. Withdrawal scores were assessed using the Opioid and Benzodiazepine Withdrawal Score. Withdrawal scores were assessed on any patient receiving any form of opioid or benzodiazepine for greater than 5 days or if there was provider concern of withdrawal symptoms during the weaning of sedation.
Daily total opioid and benzodiazepine dose from the day before dexmedetomidine initiation to 48 hours after dexmedetomidine discontinuation was recorded and calculated as intravenous morphine and lorazepam equivalents. To assess significance of hemodynamic variability, vasoactive medication dosing was recorded at initiation, throughout dexmedetomidine administration, and after discontinuation. The use of atropine for bradycardia or saline bolus for hypotension within 4 hours of dexmedetomidine initiation was recorded. The addition of any antihypertensive within 48 hours after dexmedetomidine discontinuation and the addition of clonidine at any time during dexmedetomidine use were also noted.
Basic descriptive statistics for patient characteristics are presented as proportions for categorical variables and median and range for continuous variables. Paired-sample t tests were used to estimate the mean difference in blood pressure, HR, and comfort score after initiation and discontinuation of dexmedetomidine at the various time points noted above. Wilcoxon matched-pairs signed-rank tests were used to compare daily total cumulative opiate and benzodiazepine dosing. Statistical analyses were performed using Excel and Stata software, version 10 (StataCorp LP, College Station, TX).
Materials and Methods
Study Design and Setting
The study was approved by the Institutional Review Board of Seattle Children's Hospital, which waived the need for informed consent. We performed a retrospective, observational study of patients in the PICU, cardiac ICU, and neonatal ICU at Seattle Children's between December 1, 2008, and December 1, 2010. Unit protocols at the time of this study included starting dose of 0.2 μg/kg/hr, max dose of 0.7 μg/kg/hr, and use for up to 48 hours unless approved by the unit medical director for longer duration.
Study Population
We included all patients less than 21 years old who had received a continuous infusion of dexmedetomidine longer than 72 hours. Exclusion criteria include greater than or equal to21 years, inability to obtain clinical information, or discontinuation of dexmedetomidine for any length of time during the first 72 hours. Patients were identified using our information technology database, discern analysis, that enabled us to identify patients with pharmacy charges for dexmedetomidine use longer than 72 hours.
Data Collection
Each patient's record was searched for major diagnosis and surgical procedures. Indication for starting dexmedetomidine, initiation and discontinuation times, initial and maximum dose, duration of use, and the utilization of dexmedetomidine wean were recorded. Blood pressure and heart rate (HR) were recorded for each patient at initiation (considered baseline), 30 minutes and 1, 2, and 72 hours of use, as well as at discontinuation, 30 minutes and 1, 2, 4, 24, and 48 hours after discontinuation. These intervals were chosen given the mean distribution half-life of approximately 10 minutes, duration of action of 4 hours, and the terminal elimination half-life of 2.7 hours.
Given recent work in our institution on sedation protocols by Deeter et al, we used our established Seattle PICU Comfort Score to assess depth of sedation (Table 1). This sedation protocol was used in both the PICU and the cardiac ICU (CICU), whereas the newborn ICU (NICU) had an adjusted regimen. The typical progression of sedation in the PICU and CICU was opioid infusion and as needed intermittent benzodiazepine dosing. If increased sedation was needed, our sedation protocol instructed the addition of a benzodiazepine infusion. After this addition, it was physician preference whether to add a dexmedetomidine infusion or to increase both opioid and benzodiazepine infusion doses. The NICU protocol was similar with the exception that benzodiazepine infusions were not recommended.
Dexmedetomidine infusions were noted to either be weaned off or stopped abruptly. There was not a dexmedetomidine unit protocol or common practice at the time of this study. In regards to opioid and benzodiazepine weaning, it was unit practice to stop the infusions abruptly if on for less than 5 days or wean daily by 20% of the maximum daily dose every day if on for 5–10 days. For those on for greater than 10 days, the opioid and benzodiazepine infusions were typically weaned by 10% on alternating days. However, there was variability based on provider preference and patient tolerance of wean. There was no protocol in place directing which agent should be weaned or discontinued first. However, dexmedetomidine was typically discontinued first, but there was variability among providers. Withdrawal scores were assessed using the Opioid and Benzodiazepine Withdrawal Score. Withdrawal scores were assessed on any patient receiving any form of opioid or benzodiazepine for greater than 5 days or if there was provider concern of withdrawal symptoms during the weaning of sedation.
Daily total opioid and benzodiazepine dose from the day before dexmedetomidine initiation to 48 hours after dexmedetomidine discontinuation was recorded and calculated as intravenous morphine and lorazepam equivalents. To assess significance of hemodynamic variability, vasoactive medication dosing was recorded at initiation, throughout dexmedetomidine administration, and after discontinuation. The use of atropine for bradycardia or saline bolus for hypotension within 4 hours of dexmedetomidine initiation was recorded. The addition of any antihypertensive within 48 hours after dexmedetomidine discontinuation and the addition of clonidine at any time during dexmedetomidine use were also noted.
Statistical Analysis
Basic descriptive statistics for patient characteristics are presented as proportions for categorical variables and median and range for continuous variables. Paired-sample t tests were used to estimate the mean difference in blood pressure, HR, and comfort score after initiation and discontinuation of dexmedetomidine at the various time points noted above. Wilcoxon matched-pairs signed-rank tests were used to compare daily total cumulative opiate and benzodiazepine dosing. Statistical analyses were performed using Excel and Stata software, version 10 (StataCorp LP, College Station, TX).