Respiratory Depression in Young Prader Willi Syndrome Patients following Clonidine Provocation for Growth Hormone Secretion Testing

Abstract

Objectives. To determine the sedative and respiratory effects of clonidine when used to evaluate growth hormone (GH) secretion in children with Prader Willi Syndrome (PWS). Methods. The study prospectively evaluated children with PWS who received clonidine (0.15 mg/m2) to assess GH responsiveness. Patients were studied up to four times over three years. Vital signs, oxygen saturation, and sedation level were recorded at baseline and every five minutes following clonidine. Changes between baseline and post-clonidine were evaluated using a repeated measurement analysis. Results. Sixty studies were performed on 17 patients, mean age 30.4 ± 15.0 months. The mean ± SD dose of clonidine was 0.074 ± 0.027 mg (5.3 ± 1.72 mcg/kg). All patients achieved a sedation score of 4 to 5 (drowsy to asleep). Mean declines in respiratory rate (7.5 ± 6.1 breaths/min; P < .001), and oxygen saturation (2.2 ± 2.0%; P < .001) occurred following clonidine. Five patients (29%) experienced oxygen saturations ≤94% on nine occasions. Three oxygen desaturations were accompanied by partial airway obstruction. Conclusions. Clonidine doses to assess GH secretion often exceed doses used for sedation and result in significant respiratory depression in some children with PWS. There was no association between oxygen desaturation and BMI.

Effect of body mass index on the growth hormone response to clonidine stimulation testing in children with short stature

“…Various stimulation tests for GH secretion have been proposed over the years, each with its own advantages and limitations. 31 Hollmann et al 32 have recently shown that clonidine administration caused respiratory depression in some children with Prader-Willi syndrome. Of note is the fact that the usefulness of the clonidine test is limited to the paediatric age, because in adult subjects, the GH response to the drug was not different from that after placebo.…”

“…2 Clonidine is an alpha-receptor agonist that stimulates GH secretion by a central mechanism probably by inducing endogenous GHRH release 26,27 and, among the various GH provocative tests, is one of the most widely used 28,29 in children. 32 However, respiratory dysfunction is a common finding in patients with Prader-Willi syndrome, contributing significantly to morbidity and early mortality in this population. 30 In our centre, the clonidine test is routinely used to evaluate GH secretion in children with short stature and/or poor growth velocity.…”

“…30 In our centre, the clonidine test is routinely used to evaluate GH secretion in children with short stature and/or poor growth velocity. 31 Hollmann et al 32 have recently shown that clonidine administration caused respiratory depression in some children with Prader-Willi syndrome. 32 However, respiratory dysfunction is a common finding in patients with Prader-Willi syndrome, contributing significantly to morbidity and early mortality in this population.…”

“…31 Hollmann et al 32 have recently shown that clonidine administration caused respiratory depression in some children with Prader-Willi syndrome. 32 However, respiratory dysfunction is a common finding in patients with Prader-Willi syndrome, contributing significantly to morbidity and early mortality in this population. Although the respiratory system was never specifically studied in our subjects during clonidine testing, our children are closely monitored throughout the test, and none had ever experienced respiratory problems.…”