Enteral absorption and haemodynamic response of clonidine in infants post-cardiac surgery

TY - JOUR

T1 - Enteral absorption and haemodynamic response of clonidine in infants post-cardiac surgery

AU - Arenas-Lopez, S.

AU - Mulla, H.

AU - Manna, S.

AU - Durward, A.

AU - Murdoch, I. A.

AU - Tibby, S. M.

PY - 2014/12

Y1 - 2014/12

N2 - 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 mu g 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 C-max ranging from 0.15 to 1.55 ng ml(-1) (median 0.73), and T-max 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 T-max (interaction effect P=0.03); this was not seen among those receiving inotropes. The haennodynamic 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 V-d 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.

AB - 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 mu g 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 C-max ranging from 0.15 to 1.55 ng ml(-1) (median 0.73), and T-max 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 T-max (interaction effect P=0.03); this was not seen among those receiving inotropes. The haennodynamic 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 V-d 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.

KW - cardiac surgical procedures

KW - clonidine

KW - infants

KW - INTRAVENOUS CLONIDINE

KW - OXYGEN-CONSUMPTION

KW - ORAL CLONIDINE

KW - CHILDREN

KW - PHARMACOKINETICS

KW - SEDATION

U2 - 10.1093/bja/aeu258

DO - 10.1093/bja/aeu258

M3 - Article

SN - 0007-0912

VL - 113

SP - 964

EP - 969

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

IS - 6

ER -