Plasma Concentrations Following Application of Whole versus Cut Transdermal Clonidine Patches To Critically Ill Children

Abstract

Clonidine is used for hypertension and narcotic withdrawal prophylaxis in adults and children. This study described plasma absorption of clonidine from whole and cut transdermal clonidine patches. This was a retrospective descriptive study in an 18 bed multidisciplinary pediatric intensive care unit, evaluating 15 critically ill children with a median age of 1.1 years (range 0.3-11 years) treated with transdermal clonidine for narcotic withdrawal prophylaxis, and who had plasma clonidine concentrations measured. An assessment of the relationship between clonidine dose and patch integrity (whole vs. cut) with plasma concentrations was performed, with further analysis by Spearman Correlation Coefficient. Clonidine doses averaged 7.5±4.2 µg/kg/day (range 2.3-20 µg/kg/day) for 9.8±4.3 days (range 4-20 days). There were 9 cut patches and 6 whole patches. The average prescribed dose delivered by cut patches was 6.4±3 µg/kg/day, resulting in a mean plasma concentration of 1±1.1 ng/ mL (range <0.05-3.3 ng/mL). The average prescribed dose delivered by whole patches was 7±1.7 µg/kg/day, resulting in a mean plasma concentration of 0.55±0.3 ng/mL (range 0.13-1.5 ng/mL). The Spearman Correlation Coefficient was calculated to evaluate the correlation between dose and concentration. For whole and cut patches the correlation coefficient was 0.94 (P=0.005) and 0.72 (P=0.002), respectively. Doses ranging from 1.7 to 20 µg/kg/day using whole patches resulted in no plasma concentrations >2 ng/mL. However, a plasma concentration >2 ng/mL was achieved with a dose of 8.8 µg/kg/day delivered by a cut patch. In addition, the 2 samples that resulted in undetectable concentrations were taken from patients who were treated with cut patches. The results from this pilot study suggest that critically ill children absorb clonidine from transdermal patches, but the rate and extent of absorption appears to be more predictable with the use of whole patches compared to patches that have been cut.

Clonidine for Sedation and Analgesia and Withdrawal in Critically Ill Infants and Children

“…Based on a review of the published data, clonidine may provide beneficial effects as an adjunct therapy for sedation and analgesia and drug withdrawal. Thirty‐one patients (27.1%) included in this review received clonidine as part of a pharmacokinetic study that did not focus on clinical outcomes . Fifty (43.9%) received clonidine for sedation and analgesia while mechanically ventilated .…”

“…Some reports have described utilizing transparent film dressing to occlude part of the patch or cutting the patch into quarters (e.g., 0.025 mg/day) or halves (e.g., 0.05 mg/day). These practices should be discouraged because it was reported that the patients receiving cut patches had significantly higher concentrations of clonidine than those with whole patches. No pharmacokinetic data have evaluated occlusion of a clonidine patch with transparent film dressings.…”

“…Five case reports or case series and five studies including 114 children receiving clonidine were included in the review. [7][8][9][15][16][17][18][19][20][21] Tables 1-3 provide a summary of the type of report, clonidine dosing regimen, and main results.…”

“…The population estimate of half‐life is 44–72 hours in neonates and 8–12 hours in children who are not critically ill. However, there is a paucity of data evaluating the pharmacokinetic profile of transdermal and enteral (PO) clonidine in critically ill neonates and children …”

“…However, there is a paucity of data evaluating the pharmacokinetic profile of transdermal and enteral (PO) clonidine in critically ill neonates and children. [7][8][9][10] Clonidine has been used off label in the pediatric intensive care unit (PICU) and neonatal intensive care unit (NICU) for a number of different indications including sedation and analgesia, drug withdrawal, and neonatal abstinence syndrome (NAS). Recent data suggest that opioids and benzodiazepines have negative effects on the developing brain, whereas dexmedetomidine may have neuroprotective effects according to preliminary data from animal studies with dexmedetomidine.…”