title: Enteral absorption and haemodynamic response of clonidine in infants post-cardiac surgery.
abstract: BACKGROUND
  Clonidine is a useful analgesic-sedative agent; however, few data exist regarding its use in infants after congenital heart disease surgery. We thus aimed to assess the absorption and safety of enterally administered clonidine in this setting.
  
  
  METHODS
  Sixteen infants (median age 6.7 months) received a single nasogastric dose of 3 μg kg(-1) clonidine 2-6 h after surgery. Blood samples were obtained at seven time intervals (up to 480 min). Plasma concentration profiles were obtained, and then pooled with a previous study (137 samples, 30 infants) for estimation of population pharmacokinetic parameters (NONMEM version 7.2).
  
  
  RESULTS
  Enteral absorption showed considerable inter-individual variability, with clonidine Cmax ranging from 0.15 to 1.55 ng ml(-1) (median 0.73), and Tmax from 12 to 478 min (median 190). Although therapeutic sedative plasma concentrations were achieved in 94% of patients, only half had attained this by 70 min post-dose. Patients who did not receive inotropes exhibited a positive association between cumulative morphine dose and Tmax (interaction effect P=0.03); this was not seen among those receiving inotropes. The haemodynamic profile was favourable; few patients required fluid boluses, and this bore no relationship to plasma clonidine concentration. Population pharmacokinetic parameter estimation yielded results similar to previous paediatric studies: clearance 13.7 litre h(-1) 70 kg(-1) and Vd 181 litre 70 kg(-1).
  
  
  CONCLUSIONS
  Early postoperative enteral clonidine produces favourable haemodynamic profiles and therapeutic plasma concentrations in the majority of cardiac surgical infants; however, the time to achieve this can be erratic. Thus, parenteral administration may be preferable if rapid analgo-sedative effects are needed.
authors: Department of Pharmacy, Evelina London Children's Hospital, Guy's & St Thomas' NHS Foundation Trust, King's Health Partners, Westminster Bridge Road, London SE1 7EH, UK.
authors: S
authors: S
authors: Arenas-Lopez
authors: Department of Pharmacy, University Hospitals of Leicester, Groby Road, Leicester, UK.
authors: H
authors: H
authors: Mulla
authors: Department of Paediatric Intensive Care, Evelina London Children's Hospital, Guy's & St Thomas' NHS Foundation Trust, King's Health Partners, Westminster Bridge Road, London SE1 7EH, UK.
authors: S
authors: S
authors: Manna
authors: Department of Paediatric Intensive Care, Evelina London Children's Hospital, Guy's & St Thomas' NHS Foundation Trust, King's Health Partners, Westminster Bridge Road, London SE1 7EH, UK.
authors: A
authors: A
authors: Durward
authors: Department of Paediatric Intensive Care, Evelina London Children's Hospital, Guy's & St Thomas' NHS Foundation Trust, King's Health Partners, Westminster Bridge Road, London SE1 7EH, UK.
authors: I A
authors: IA
authors: Murdoch
authors: Department of Paediatric Intensive Care, Evelina London Children's Hospital, Guy's & St Thomas' NHS Foundation Trust, King's Health Partners, Westminster Bridge Road, London SE1 7EH, UK shane.tibby@gstt.nhs.uk.
authors: S M
authors: SM
authors: Tibby
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000008:administration & dosage; D003000:Clonidine / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D004334:Drug Administration Schedule; D006330:Heart Defects, Congenital / Q000601:surgery*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D007223:Infant; D007408:Intestinal Absorption; D007441:Intubation, Gastrointestinal; D008954:Models, Biological; D009020:Morphine / Q000008:administration & dosage; D010149:Postoperative Pain / Q000097:blood / Q000517:prevention & control; D011182:Postoperative Care / Q000379:methods; D011184:Postoperative Period
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D009020:Morphine; D003000:Clonidine
keywords: cardiac surgical procedures; clonidine; infants