Endotracheal instillation of prostacyclin in preterm infants with persistent pulmonary hypertension

Does endotracheal instilled prostacyclin (epoprostenol) improve oxygenation in preterm infants with persistent pulmonary hypertension? Four preterm infants were studied. Prostacyclin (50 ng x kg(-1)) was injected as an endotracheal bolus. In two patients the prostacyclin bolus was repeated and in one patient prostacyclin was administered continuously. Oxygenation was evaluated through the oxygenation index and the ratio of arterial oxygen tension to the fraction of inspired oxygen. The mean arterial blood pressure was used to evaluate systemic circulation. The oxygenation index (+/-SD) decreased significantly from 39 (+/-13.3) to 7 (+/-2.5) and the ratio of arterial oxygen tension to the fraction of inspired oxygen (+/-SD) increased significantly from 47 (+/-13) to 218 (+/-67), most likely related to a reduction of the pulmonary vascular resistance with a reversal of the extrapulmonary shunting at the ductus arteriosus and atrial level. The blood pressure did not change. All effects were reversed on drug withdrawal. Repeated or continuous endotracheal administration of prostacyclin in three children demonstrated a sustained response without tachyphylaxis, and without overt side-effects. Endotracheal instillation of prostacyclin resulted in an improved oxygenation without systemic vascular repercussions in four preterm infants with persistent pulmonary hypertension. Repeated or continuous administration showed a sustained response and no overt side-effects were noticed

CYP3A5 variant allele frequencies in Dutch Caucasians

BACKGROUND: Enzymes of the cytochrome P450 3A (CYP3A) family are responsible for the metabolism of >50% of currently prescribed drugs. CYP3A5 is expressed in a limited number of individuals. The absence of CYP3A5 expression in approximately 70% of Caucasians was recently correlated to a genetic polymorphism (CYP3A5*3). Because CYP3A5 may represent up to 50% of total CYP3A protein in individuals polymorphically expressing CYP3A5, it may have a major role in variation of CYP3A-mediated drug metabolism. Using sequencing, have been identified (Hustert et al. Pharmacogenetics 2001;11:773-9; Kuehl et al. Nat Genet 2001;27:383-91) variant alleles *2 through *7 for CYP3A5. Detection of CYP3A5 variant alleles, and knowledge about their allelic frequency in specific ethnic groups, is important to establish the clinical relevance of screening for these polymorphisms to optimize pharmacotherapy. METHODS: In a group of 500 healthy Dutch Caucasian blood donors, we determined the allelic frequency of the CYP3A5*2, *3, *4, *5, *6, and *7 alleles by use of newly developed PCR-restriction fragment length polymorphism assays. RESULTS: The frequency of the defective CYP3A5*3 allele in the Dutch Caucasian population was 91%, followed by the CYP3A5*2 (1%) and CYP3A5*6 (0.1%) alleles. The CYP3A5*4, *5, and *7 alleles were not detected. CONCLUSIONS: On the basis of its allelic frequency, screening for the CYP3A5*3 allele in the Caucasian population is extremely relevant. In addition, screening for the CYP3A5*2 allele may be taken into consideration in individuals heterozygous for the CYP3A5*3 allele. The CYP3A5*4, *5, *6, and *7 alleles have low allelic frequencies that do not support initial screening

Age- and therapy-related effects on morphine requirements and plasma concentrations of morphine and its metabolites in postoperative infants

BACKGROUND: To investigate clinical variables such as gestational age, sex, weight, the therapeutic regimens used and mechanical ventilation that might affect morphine requirements and plasma concentrations of morphine and its metabolites. METHODS: In a double-blind study, neonates and infants stratified for age [group I 0-4 weeks (neonates), group II > or =4-26 weeks, group III > or =26-52 weeks, group IV > or =1-3 yr] admitted to the paediatric intensive care unit after abdominal or thoracic surgery received morphine 100 micro g kg(-1) after surgery, and were randomly assigned to either continuous morphine 10 micro g kg(-1) h(-1) or intermittent morphine boluses 30 micro g kg(-1) every 3 h. Pain was measured using the COMFORT behavioural scale and a visual analogue scale. Additional morphine was adm

Unlicensed and off-label prescription of respiratory drugs to children

Many respiratory drugs are not available in formulations suitable for infants and toddlers. Efficacy and safety research is mostly restricted to older children. However, respiratory drugs are frequently used in children for common diseases like asthma, upper and lower respiratory tract infections, rhinitis and sinusitis. The unlicensed and off-label use of respiratory drugs in children were studied. A population-based cohor

Waiting 2 minutes after sucrose administration-unnecessary?

Background Worldwide, oral sucrose is standard of care in many neonatal intensive care units to relieve procedural pain in neonates. This study aims to determine if time interval between sucrose administration and heelstick correlates with pain scores. Methods Neonates were prospectively studied with variable time intervals and assessed with the Premature Infant Pain Profile-Revised (PIPP-R). Results 150 neonates were included with a median gestational age of 30+6 (IQR 27+6-33+2) weeks and a median time interval of 72 (IQR 39-115) seconds between sucrose administration and heelstick. In multiple regression analysis, this time interval was not significantly related to the PIPP-R (B=0.004, 95% CI -0.005 to 0.013, p=0.37). Providing non-nutritive sucking combined with sucrose was significantly related to lower PIPP-R scores (B=-3.50, 95% CI -4.7 to -2.3, p<0.001). Conclusions Our study suggests that there is no need to wait 2 min after sucrose administration before a painful procedure. Sucrose-induced non-nutritive sucking shows a fast pain-relieving effect in neonates