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

The need for sedation and analgesia and treatment of iatrogenic drug withdrawal is common in critically ill children. First-line therapy typically includes opioid agonists. However, clonidine, a central alpha(2) agonist, has been suggested as a treatment option for sedation and analgesia and iatrogenic drug withdrawal. Therefore, we conducted a literature search to identify articles evaluating the use of enteral (PO) and trans-dermal clonidine in critically ill infants and children for sedation and analgesia and treatment of iatrogenic drug withdrawal. The literature search was limited to English-language articles in Medline (1946-May 2016), Embase (1988-May 2016), and International Pharmaceutical Abstracts (1970-May 2016). Reference citations from relevant articles were also reviewed. Ten case reports and studies, representing a total of 114 children receiving clonidine, were included. Fifty patients (43.9%) received clonidine for sedation and analgesia while mechanically ventilated, and 33 (29.0%) received clonidine for treatment or prevention of drug withdrawal. The remaining 31 patients (27.1%) were included in a pharmacokinetic study that did not evaluate clinical outcomes. Seventy-nine patients (69.3%) received PO clonidine, with a dosage range of 2-15 mu g/kg/day divided every 6-8 hours. Thirty-five patients (30.7%) received transdermal clonidine, with a dosage range of 2.3-20 mu g/kg/day. Whole, cut, and occluded transdermal patches were used in the reports. Patients receiving cut patches had more variable and significantly higher serum clonidine concentrations than those receiving whole patches. Only three studies reported that the PO clonidine dose was tapered at the end of therapy; however, no report specifically described the process. The two most common adverse events reported with PO and transdermal clonidine were bradycardia and hypotension. PO and transdermal clonidine have a potential role for sedation and analgesia and drug withdrawal in critically ill infants and children. The use of cut transdermal patches should be avoided. Future prospective studies are needed to further define clonidine's role as adjunct therapy or monotherapy.