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

Prader Willi Syndrome (PWS) is a complex genetic disorder associated with abnormalities of respiratory control [1–6]. Respiratory dysfunction contributes to significant morbidity and early mortality in this population [7–9]. Pulmonary problems include decreased respiratory muscle function and a propensity for upper airway obstruction due to pharyngeal hypotonia and narrowness [6, 8]. Abnormalities in respiratory function are particularly common during sleep and are characterized by impaired ventilatory and arousal responses to hypoxia and hypercapnia in both adult and pediatric patients with PWS [5]. Sleep disordered breathing is one of the minor diagnostic criteria for PWS [10] and encompasses the entire spectrum of sleep-related disturbances from alveolar hypoventilation and hypoxemia to obstructive sleep apnea [11–13].Clonidine is a central alpha2-adrenergic receptor agonist used as a provocative agent to assess growth hormone (GH) secretion but also has analgesic and sedative properties and is used as a preanesthetic medication in adults and children [14]. Unlike most sedatives clonidine has minimal clinically significant respiratory depressant effects (decrease in oxygen saturation of ≤1%) in healthy adults when used at oral doses of 3 to 4？g/kg [15]. Similarly, in healthy children no oxygen saturations <95% were observed at oral clonidine doses of 4？g/kg as a preanesthetic [16]. However, studies specifically assessing respiratory drive demonstrate reductions in minute ventilation and carbon dioxide responsiveness in otherwise healthy subjects following clonidine administration [15, 17]. The respiratory depressant effects are more evident and even life threatening when large doses of clonidine are given, particularly in cases of clonidine overdose [17–21].The aim of this study was to assess the respiratory and sedative effects of clonidine in children with PWS when used as a provocative test for GH stimulation. We hypothesized that PWS patients, a patient popul