The pharmacokinetics of morphine was studied in 27 infants receiving a single intravenous dose of 0.1 mg/kg morphine after surgery (n = 23) or during mechanical ventilation (n = 4). The pharmacokinetics of morphine varied greatly between the subjects, especially in the neonates. The clearance and half-life varied distinctly with postnatal age. The mean (+/- SD) half-life was 8.1 +/- 8.1 h in 10 neonates younger than 1 week, 5.4 +/- 3.4 h in 10 infants aged from 1 week to 2 months and 2.6 +/- 1.7 h in 7 infants aged from 2 to 6 months. Mean clearance increased significantly with age, being 8.7 +/- 5.8 ml/min/kg in the youngest age group, 11.9 +/- 5.1 ml/min/kg in those aged 1 week to 2 months and 28.0 +/- 8.9 ml/min/kg in those aged 2-6 months, and was also significantly lower in the critically ill infants. The clearance and half-life of morphine begin to approach adult values after the age of 1 month, but great individual variability exists even after that. In order to reduce the risk of overdosing or underdosing, the dose of morphine should be titrated individually.
The authors evaluated whether alfentanil could be given before treatment procedures in critically ill mechanically ventilated neonates without adverse effects. Alfentanil (mean dose 11.7 micrograms/kg, range 9-15) was given intravenously to 20 mechanically ventilated critically ill newborn infants (mean birth weight 2510 g, range 1490-3990) during the first 3 days of life before treatment procedures. Heart rate, arterial blood pressure, transcutaneous partial pressure of O2, respiratory rate, and general activity were observed continuously from 10 min before the administration of alfentanil until 1 h after it. Plasma alfentanil concentrations were measured in 15 subjects. The pharmacokinetics of alfentanil varied greatly among the subjects. The hemodynamic changes were not clinically significant, and the most important side effect was muscle rigidity. Nine infants had mild or moderate rigidity, which had little or no effect on ventilation. Four infants had severe rigidity and jerking comparable to convulsive activity, transiently impairing ventilation and oxygenation for approximately 5-10 min. Increased inspired oxygen and increased pressure by manual ventilation were needed to prevent hypoxemia. Electroencephalographic recordings for three infants during alfentanil administration showed no evidence of increased seizure activity. We conclude that alfentanil should not be used for newborn infants without simultaneous muscle relaxation because of the danger of rigidity.
AIM: To evaluate the trends in the incidence, clinical course and outcome of respiratory distress syndrome (RDS) in the newborn in the Oulu University Hospital region in northern Finland. METHODS: In the population of 58 990 infants, the incidence rates of RDS specific to gestational age and birthweight in two consecutive periods, 1990-95 and 1996-99, were calculated. Clinical course and other neonatal morbidities were reported. All surviving infants were followed up until 1 y of corrected age. RESULTS: The overall incidence of RDS did not change significantly (8.7/1000 livebirths in 1990-95 vs 7.6 in 1996-99; p = 0.15), but the gestational age-adjusted incidence decreased between the two consecutive periods (p = 0.005). The frequency of infants with gestational age below 28 wk tended to increase towards the late 1990s, while their RDS incidence remained unchanged. RDS-related neonatal mortality decreased in parallel with neonatal mortality, accounting for 15% of all neonatal deaths. The duration of oxygen therapy shortened (8.0 vs 5.5 d) and the incidence of pneumothorax decreased (9.7 vs 4.1%), whereas the rate of chronic lung disease at 36 wk of postconceptional age (16.4 vs 16.7%) and at 1 y of corrected age (9.2 vs 8.2%) remained unchanged, as did also associated neurosensory morbidity (8.8 vs 9.5%). CONCLUSION: During the 1990s, the incidence of RDS shifted towards more immature infants and the gestational-age specific incidence decreased. The course of the disease shortened and acute complications decreased. The frequency of chronic pulmonary sequelae (and associated neurosensory morbidity) at the age of 1 y did not change significantly.
OBJECTIVE: Fulminant early-onset neonatal pneumonia is associated with ascending intrauterine infection (IUI), prematurity, persistent pulmonary hypertension (PPHN), and septicemia. Nitric oxide (NO) as an inflammatory mediator is included in antimicrobial defense and has a role in pathogenesis of septic shock. The aim was to study the role of inflammatory NO in neonatal pneumonia. METHODS: Lungs from 36 autopsies were studied: 12 had fulminant early-onset neonatal pneumonia, 5 pneumonia of later onset, and 19 controls had similar gestational and postnatal age. In addition, airway specimens from 21 intubated newborns were analyzed: 7 with fulminant early-onset pneumonia, 7 apparently noninfected infants born prematurely attributable to IUI, and 7 premature infants of similar gestation. Specimens were analyzed for inducible NO synthase (NOS2) and nitrotyrosine, an indicator of NO toxicity. The degree of staining was analyzed. RESULTS: In fulminant pneumonia, alveolar macrophages (AM) showed significantly less NOS2 immunoactivity than the controls. In the airway specimens, the infants with fulminant pneumonia 0 to 2 days after birth had significantly lower intracellular NOS2 and nitrotyrosine and significantly lower interleukin-1beta and surfactant protein-A than apparently noninfected IUI infants. NOS2 and the other indices increased significantly during the recovery. CONCLUSIONS: For the first time, we report NOS2 expression by macrophages from human neonates. In fulminant early-onset neonatal pneumonia, delayed production rather than excess of pulmonary inflammatory NO is associated with severe symptoms.
The effects of analgesia on plasma beta-endorphin (beta-E), serum cortisol and blood glucose responses were investigated in 20 distressed, mechanically ventilated neonates during the first 3 days of life. Morphine 0.1 mg/kg, meperidine 1 mg/kg or alfentanil 10 micrograms/kg were used for analgesia as clinically indicated. Plasma beta-E, serum cortisol and blood glucose were recorded before analgesia and 1 and/or 2, 12 and 24 h afterwards in the distress group and once in 20 healthy neonates (control group). beta-E, cortisol, and blood glucose before analgesia were significantly higher in the distress group than in the control group. Cortisol values had decreased significantly 2 h after analgesia and blood glucose within 12 h. Plasma beta-E values had decreased to the same level as in the controls 24 h after the start of analgesia. The results indicate that the stress response in the distressed neonates with cardiorespiratory problems, as assessed by beta-E, cortisol, and blood glucose, is attenuated by opioid medication, and it is concluded that these patients should be given adequate analgesia.
AIM: Nitric oxide (NO) is an important mediator required for neonatal pulmonary circulatory adaptation and for pulmonary defence. Both deficient and excessive NO production have been proposed to play a role in neonatal lung disease. This study aimed to establish a method that allows direct measurement of exhaled and nasal NO concentrations in newborn infants who require intubation and ventilation. METHODS: A rapid-response chemiluminescence NO analyser was used. Gas was sampled from the endotracheal intubation tube, and tidal volumes and flow rates were measured. The nasal NO was sampled from the non-intubated nostril. The accuracy of the method was validated using a lung model. NO levels from six preterm and six term/near-term newborns were studied. Measurements were performed on a daily basis during the first week. RESULTS: An expiration >0.2 s in duration with a flow rate >1.7 ml s(-1) could be accurately analysed for the presence of >1 parts per billion of NO. The very preterm infants with neonatal lung disease had a different postnatal NO output pattern from the lower and upper airways compared with the ventilated term/near-term infants. CONCLUSION: A novel method for measurement of exhaled NO of an intubated newborn is presented. The possible association of exhaled NO concentration with the development of chronic lung disease remains to be studied.
The aims of this prospective nationwide investigation were to establish the birth rate, mortality, and morbidity of extremely low birth weight (ELBW) infants in Finland in 1996-1997, and to analyze risk factors associated with poor outcome.
The study population included all stillborn and live-born ELBW infants (birth weight: 12 hours, the overall incidence of respiratory distress syndrome (RDS) was 76%; of blood culture-positive septicemia, 22%; of IVH grades II through IV, 20%; and of necrotizing enterocolitis (NEC) with bowel perforation, 9%. The rate of IVH grades II through IV and NEC with bowel perforation decreased with increasing gestational age, but the incidence of RDS did not differ significantly between GWs 24 to 29. A total of 5 infants (2%) needed a shunt operation because of posthemorrhagic ventricular dilatation. Two hundred eleven ELBW infants (40% of all and 60% of live-born infants) survived until discharge or to the age corresponding with 40 GWs. The oxygen dependency rate at the age corresponding to 36 GWs was 39%, and 9% had ROP stage III-V. Neurological status was considered completely normal in 74% of the surviving infants. The proportions of infants born at 22 to 23, 24 to 25, 26 to 27, and 28 to 29 GWs with at least one disability (ROP, oxygen dependency, or abnormal neurological status) at the age corresponding to 36 GWs were 100%, 62%, 51%, and 45%, respectively. Birth weight
To study neurodevelopmental outcome in a two year cohort of extremely low birthweight (ELBW) infants at 18 months corrected age, to compare the development of the ELBW infant subcohort with that of control children, and to find risk factors associated with unfavourable outcome.
All 211 surviving ELBW infants (birth weight
Notes
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AIM: Premature infants with respiratory failure and early-onset pneumonia have low inducible nitric oxide synthase (NOS2) and no evidence of nitric oxide (NO) toxicity. However, inhalation of NO may not be indicated in sepsis because excessive NO generation has been reported. This prospective study was designed to test the hypothesis that inhaled NO is effective in a select group of small premature infants and that the responsiveness to NO is associated with low NOS2 enzyme. METHODS: 246 very low birthweight infants (birthweight 40, arterial-alveolar ratio for oxygen tension
This paper reports two mechanically ventilated preterm babies who received overdoses of pethidine in the neonatal period. One of the neonates (gestational age 26 weeks, birthweight 1040 g) received repeated appropriate doses, which resulted in central nervous system irritability and convulsion due to accumulation of the drug and its metabolite, norpethidine. The other neonate (gestational age 27 weeks, birthweight 980 g) received a major (10-fold) overdose with little clinical effect. These two cases indicate notable individual variability in the responses of babies to pethidine. This is typical of other opioids, too. Therefore, the dosing of opioids to neonates should be titrated individually, and the patients should be observed carefully.
