ABSTRACT
BACKGROUND AND OBJECTIVES: Thiopentone, a short-acting barbiturate, has been introduced as premedication for intubation in newborn infants. The objectives of this study were to assess the pharmacokinetics of thiopentone in newborn infants, and to unravel whether placental transfer of the drug should be taken into account if administered to infants exposed to it during delivery. METHODS: Plasma concentrations were assessed with high-pressure liquid chromatography in samples from delivering mothers (n=27) receiving a median dose of 5.5 mg/kg (range 3.8-7.7) thiopentone for Caesarean section in gestational week 37.6 (range 25.7-41.4) and from corresponding umbilical cord blood (n=28). In infants (n=30) born at 35.4 weeks gestation (range 27.9-42.0) undergoing surgery at a median postnatal age of 24.5 h (range 4-521), repeated blood levels were assessed after administering a dose of 3 mg/kg thiopentone on clinical indication before intubation (seven samples per infant from 5 min to 48 h after administration). RESULTS: The umbilical/maternal concentration ratio was 0.7, the mean concentration of thiopentone was 55.7 micromol/l (SD+/-15.3) in mothers and 39.3 micromol/l (SD+/-12.5) in venous cord blood. In newborn infants undergoing surgery, the terminal half-life of thiopentone was 8 h (interquartile range (IQR) 2.5-10.8), and clearance 0.092 l/min per kg/postnatal age in days (IQR 0.02-0.1). CONCLUSIONS: Thiopentone might be used as premedication for short-lasting intubation after birth, for example, for surfactant administration. During the first 4 h after birth the dose needs to be adjusted for maternal dosage as well as for the weight of the infant.
Subject(s)
Hypnotics and Sedatives/blood , Infant, Newborn/blood , Placenta/metabolism , Thiopental/blood , Anesthesia, General/methods , Anesthesia, Obstetrical/methods , Body Weight , Cesarean Section , Chromatography, High Pressure Liquid/methods , Congenital Abnormalities/surgery , Drug Administration Schedule , Female , Fetal Blood/metabolism , Half-Life , Humans , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/pharmacokinetics , Male , Maternal-Fetal Exchange , Pregnancy , Premedication/methods , Prospective Studies , Thiopental/administration & dosage , Thiopental/pharmacokineticsABSTRACT
UNLABELLED: Thiopental may be used for sedation before intubation in newborn infants. A boy, born at 33 weeks of gestation (gw); birth weight 2435 g, was prescribed thiopental 3 mg/kg before intubation. He developed temporary hypotension and oxygen desaturation, and remained unconscious for longer than expected with a suppressed electroencephalography for 48 h. Serum thiopental concentration was 82, 59, 42 and 32 micromol/L after 20 min and 6, 24 and 68 h respectively. Serum concentrations from five newborn infants at the same time points after intubation with the same thiopental dose were used as reference values, and indicated a 10-fold overdose in the index case. The cause of the overdose could not be identified. The infant recovered; cerebral magnetic resonance imaging at the age of 42 gw and psychomotor development at 2 years were normal. These results show that thiopental concentrations are variable in neonates and there is a high risk of dosage error as no specific paediatric formulation is available. CONCLUSION: Well-designed procedures and continuous education are required to prevent errors and adverse events during drug delivery to newborn infants. To develop a safe method of administration for thiopental, an extended pharmacokinetic and pharmacodynamic study in neonates is warranted.
Subject(s)
Thiopental/adverse effects , Thiopental/pharmacokinetics , Dose-Response Relationship, Drug , Drug Overdose , Erythrocyte Transfusion , Humans , Infant, Newborn , Infant, Premature , Male , Oxygen Inhalation Therapy , Reference Values , Thiopental/blood , Unconsciousness/chemically inducedABSTRACT
We have intentionally performed heart transplantation in a 5-year-old child, despite the most unfavourable risk factors for patient survival; the presence of high level of antibodies against donor's human leucocyte antigen (HLA) class I/II and blood group antigens. Pretransplant treatment by mycophenolate mofetil, prednisolone, tacrolimus, intravenous immunoglobulin, rituximab, protein-A immunoadsorption (IA) and plasma exchange reduced antibody titres against the donor's lymphocytes from 128 to 16 and against the donor's blood group antigen from 256 to 0. The patient was urgently transplanted with a heart from an ABO incompatible donor (A(1) to O). A standard triple-drug immunosuppressive protocol was used. No hyperacute rejection was seen. Antibodies against the donor's HLA antigens remained at a low level despite three acute rejections. Rising anti-A(1) blood group antibodies preceded the second rejection and were reduced by two blood group-specific IAs and remained at a low level. The patient is doing well despite the persistence of donor-reactive antibodies.
