Randomised controlled trial of low dose fentanyl infusion in preterm infants with hyaline membrane disease.

AIM: To evaluate the effects of low dose fentanyl infusion analgesia on behavioural and neuroendocrine stress response and short term outcome in premature infants ventilated for hyaline membrane disease. METHODS: Twenty seven ventilated preterm infants were randomly assigned to receive a mean fentanyl infusion of 1.1 (0.08 SE) micrograms/kg/h for 75 (5) hours, and 28 untreated infants were considered a control group. A behavioural sedation score was used to assess the infants' behaviour. Urinary metanephrine and the normetanephrine:creatinine molar ratio were determined at 0, 24, 48 and 72 hours. Outcome data and ventilatory indexes were recorded for each infant. RESULTS: The fentanyl group showed significantly lower behavioural stress scores and O2 desaturations than controls and lower urinary concentrations of metanephrine and normetanephrine at 24, 48, 72 hours. The two groups showed no significant difference in ventilatory variables or short term outcome. CONCLUSIONS: A short course of low dose fentanyl infusion reduces behavioural sedation scores, O2 desaturations and neuroendocrine stress response in preterm ventilated infants.

Urinary arginine vasopressin: pattern of excretion in the neonatal period.

The pattern of arginine vasopressin (AVP) secretion in the immediate neonatal period is unclear. Plasma concentrations of AVP are reflected by its urinary excretion, thus providing a noninvasive method for studying the pattern of AVP release in the neonate. In these studies, we determined the pattern of urinary AVP excretion (microU/mg creatinine) during the first 2-4 days after birth in 78 neonates, 53 of whom had various prenatal and/or neonatal complications. In well term (n = 12) and preterm (n = 13) infants mean urinary AVP excretion decreased gradually during the first 24-36 h after birth. Although term and preterm infants with perinatal asphyxia had highest initial levels of urinary AVP (greater than 200 microU/mg creatinine) and a significant negative correlation with the 1-min Apgar score was obtained, their pattern of excretion was similar to respective controls. After delivery, elevated values for urinary AVP excretion were found among infants with neonatal courses complicated by intracranial hemorrhage, hypoxic encephalopathy, and pneumothorax. Urine osmolality did not correlate linearly with urinary AVP levels, but rather attained a maximum value of approximately 400 mosmol/kg at urinary AVP levels less than 200 microU/mg creatinine and then plateaued. It is concluded that the decrease in urinary AVP excretion observed soon after birth generally reflects diminution of the hypersecretion of AVP during parturition; neonates with evidence of intrapartum asphyxia initially have increased urinary AVP excretion; however, the pattern of excretion is similar to normal infants. During the neonatal period insults such as pneumothorax and intracranial hemorrhage may cause hypersecretion of this hormone.

Urinary catecholamine levels in the newborn infant.

The urinary concentrations of dopamine, noradrenaline and adrenaline were measured by a radioenzymatic method in 212 full-term and premature newborns. The ranges, means and standard deviations from birth to 4 days + are presented. The excretion of dopamine was ten times that of noradrenaline or adrenaline. The absolute concentrations of each catecholamine were reduced as birth weight decreased. The values were increased in babies with fetal distress. Any changes found in hypoglycaemic or jaundiced infants were attributable to prematurity. Very high levels were found in a few infants given tolazoline. We speculate that the role of dopamine production and excretion in the newborn has been underestimated. Dopamine may have an important role to play in the homeostatic mechanisms of the newborn.

Hyponatraemia in the first week of life in preterm infants. Part I. Arginine vasopressin secretion.

Continuous sequential urinary arginine vasopressin measurements in 14 preterm, ventilated infants suggest that both osmoreceptor and volume receptor systems are able to stimulate the prolonged secretion of arginine vasopressin from 26 weeks' gestation. The kidney is able to respond to arginine vasopressin stimulation from the first day of life and from 26 weeks' gestation. A maximum urine osmolality not exceeding 550 mOsm/kg was reached which varied with hydration of the infant. Excretion of arginine vasopressin and urine osmolality increased during deterioration of respiratory illness, mask ventilation, bilateral pneumothoraces, and severe intraventricular haemorrhage. The data show that inappropriate arginine vasopressin secretion is common during illness in the first week of life in preterm infants and that strict attention must be paid to water balance during this time.

Urinary excretion of prostaglandin E and F 2 alpha in healthy newborn infants and in infants with hyaline membrane disease.

Urinary PGE and PGF 2 alpha excretion was estimated in 11 healthy full-term (mean birth weight, 3327 g; mean gestational age, 39.2 weeks). 15 healthy preterm (mean birth weight, 1722 g; mean gestational age, 32.1 weeks) and in 9 preterm infants suffering from hyaline membrane disease (HMD) (mean birth weight: 1454 g, mean gestational age: 31 weeks). Measurements were carried out on the 1st, 3rd and 5th days of life by radioimmunoassay, using Clinical Assays Inc. RIA kits. Urinary PGE excretion on the first day of life was 3.76 +/- 0.41 ng/day, 2.43 +/- 0.65 ng/day and 1.19 +/- 0.27 ng/day for healthy full-term, healthy premature and premature infants with HMD, respectively. The differences were significant at the level of p less than 0.05. With advancing postnatal age urinary PGE excretion markedly increased in each group (p less than 0.05). Urinary PGF 2 alpha excretion on the first day was 10.8 +/- 2.0 ng/day in full-term, 6.6 +/- 2.2 ng/day in healthy premature and 4.35 +/- 1.9 ng/day in premature infants with HMD. Then an inconsistent rise could be observed without statistically significant difference between the individual groups of various postnatal age and between the different groups of the same postnatal age. The decreased renal PGE production is suggested to be involved in the pathomechanism of HMD.

Furosemide in hyaline membrane disease.

In a randomized clinical trial designed to evaluate the effect of diuresis on infants with hyaline membrane disease, seven infants were treated with furosemide (2 mg/kg intravenously) and five received 5% dextrose water in 0.225% sodium chloride (control group). Arterial blood gas analyses performed before and during the six hours after treatment showed no significant difference between control and treated infants. Urine output and urine sodium and calcium loss were significantly increased (P less than .05) in the infants receiving furosemide. The diuresis seemed to have no effect on left atrial size determined echocardiographically, whereas measurements of dynamic skinfold thickness suggested mobilization of subcutaneous water. One infant became seriously dehydrated and hypotensive secondary to a massive diuresis. We concluded that furosemide had a potent diuretic effect in infants with hyaline membrane disease but does not improve cardiorespiratory function acutely. This may be because of failure to mobilize pulmonary interstitial fluid in the time period tested. It may also be possible that the presence of pulmonary interstitial fluid does not play an important role in the impairment of gas exchange in the acute stage of hyaline membrane disease.

Urinary excretion of prostaglandin E following the administration of furosemide and indomethacin to sick low-birth-weight infants.

Urinary excretion of prostaglandin E was measured in seven sick low-birth-weight infants. Four had severe hyaline membrane disease and one had chronic bronchopulmonary dysplasia; all received furosemide. Two infants had patent ductus arteriosus and received indomethacin. Following administration of furosemide, urine volume and the excretion rates of sodium and calcium were significantly increased; such changes were not seen following the administration of indomethacin. Prostaglandin E excretion rate was increased from 0.4 +/- 0.04 to 1.3 +/- 0.2 ng/mg Cr (mean +/- SEM) following administration of furosemide, but decreased in two patients following administration of indomethacin. The present results demonstrate that furosemide enhances urinary excretion of prostaglandin E by mechanisms which may reflect an increase in prostaglandin synthesis, a decrease in prostaglandin renal metabolism, or both. Indomethacin, which is a prostaglandin synthetase inhibitor, decreases the urinary excretion of prostaglandin E. These observations suggest that furosemide therapy in patients receiving indomethacin may be ineffective.