Karen E. Pape

Postoperative morphine infusion in newborn infants: Assessment of disposition characteristics and safety

Twelve newborn infants were given morphine intravenously for postoperative analgesia. They received a continuous infusion of 6.2 to 40 micrograms/kg/hr for 9 to 105 hours (mean +/- SEM 59.5 +/- 10.2 hours); in four the infusion was preceded by a loading dose of 50 to 100 micrograms/kg. Morphine plasma concentrations correlated with the rate of infusion, but with large variability. There was a tendency for plasma morphine concentrations to decrease in some patients receiving a constant infusion rate, suggesting improvement in morphine clearance rate. Elimination half-life of morphine (13.9 +/- 6.4 hours) was significantly longer than in older children and adults (about 2 hours). Similarly, morphine concentrations in neonates receiving 20 micrograms/kg/hr for 24 hours were three times higher (52 +/- 31 ng/ml) than in older children receiving the same schedule. Two infants who received 32 and 40 micrograms/kg/hr, respectively, developed generalized seizures. Because of the apparently greater sensitivity to morphine and the lower elimination rate in newborn infants, the infused dose should not exceed 15 micrograms/kg/hr.

Periventricular infarction diagnosed by ultrasound: A postmortem correlation†

Ultrasound brain scans sometimes demonstrate increased echogenicity or cysts, or both, in the periventricular white matter, superolateral to the ventricle, in the most common site of periventricular infarction. Over 33 months, 23 preterm infants dying after 20 or more days of life were entered into this study. Superolateral echogenicity or cysts were found in 13 (57%) cases. Periventricular infarction was present at autopsy in 12 (52%) cases. Ultrasound accurately diagnosed the size, site, and extent of periventricular infarction in 78% of scans. Interpretive errors were made with poor-quality scans and with early and late studies. We conclude that sector ultrasound brain scans accurately diagnose major periventricular infarction. Hemorrhage into the site of infarction is not a prerequisite for diagnosis of periventricular infarction by ultrasound.

Intravenous paraldehyde for seizure control in newborn infants

We studied 14 newborn infants with seizures after birth asphyxia or other causes. Paraldehyde was given as a 200 mg/kg IV bolus followed by an infusion of 16 mg/kg/h (10 cases), or as a 400 mg/kg bolus (4 cases). Serum concentrations of paraldehyde were higher in periods of adequate seizure control than in periods of little or no response. Paraldehyde serum concentrations above 10 mg/dl were associated with anticonvulsant effects and were achieved in most neonates with a 2-hour infusion of 200 mg/kg/h. If there is no effect, serum concentrations are probably below 10 mg/dl and an additional 200 mg/kg can be given safely over 1 hour.

Diagnostic accuracy of neonatal brain imaging: A postmortem correlation of computed tomography and ultrasound scans

The aim of this study was to validate brain imaging techniques in the preterm infant. A homogeneous group of very immature (less than 32 week) neonates dying in the neonatal period were sequentially scanned with linear-array real-time ultrasound scans, and after death with compound B static sector ultrasound and high-resolution computed tomography (CT) scans. All three imaging techniques were correlated with the autopsy results. All germinal matrix bleeds greater than 5mm in size and intraventricular hemorrhages associated with ventricular dilation or distortion were accurately diagnosed. In the immature infant it was difficult to distinguish the normal highly vascular germinal matrix and choroid plexus from hemorrhage into the brain or ventricles, respectively. Further studies that address the questions of accurate timing and incidence of bleeds must consider the spatial resolution of the individual scanner, the maturity of the brain, the site and size of the lesion, and the evolution of the lesion. For the diagnosis of major hemorrhagic lesions in the preterm infant, either ultrasound or CT scans may be used with confidence.

Peripheral median nerve damage secondary to brachial arterial blood gas sampling

Examination at 18 months post-term of 139 infants of birth weight ≤1,500 gm revealed 18 instances (13%) of persistent median nerve damage. All affected infants had received frequent percutaneous brachial artery punctures as neonates. Block sections of the cubital fossa done at autopsy on 12 randomly selected very low-birth-weight infants showed perineural hemorrhage, and Wallerian degeneration or traumatic neuroma of the median nerve in eight patients. It is recommended that brachial artery punctures be avoided whenever possible in the neonatal period.

INTRAUTERINE GROWTH RETARDATION (IUGR): AN ADDED RISK TO THE PRETERM INFANT

In order to determine the dual effects of IUGR and premature birth, a prospective study of growth and development was done in a group of preterm small-for-gestational age infants (SGA). All were ≤ 32 weeks gestation with hirth weights more than 2 standard deviations below the mean for gestation. During 1974, 60 infants meeting these criteria were referred to our neonatal intensive care unit. Twenty-six of the 29 survivors were followed to age 18 months post-term. Mean birth weight was 988±152 g, gestation 30.5±1.7 weeks. Each infant was randomly paired with a surviving infant of appropriate weight for gestation (AGA) who matched for birth weight, sex, and type of ventilatory support (birth weight 999±129 g, gestation 27.8±1.5 weeks). The SGA infants were significantly smaller at 18 months post-term than the AGA controls with a mean difference in weight of 0.8 kg, length 2.2 cm, head circumference 1.3 cm (p<0.005). Eight of the 26 SGA children had major neurological defects: 1 with microcephaly, 2-hydrocephaly, 4-cerebral palsy, 1-seizure disorder. None of the controls were so affected (p<0.005). The Bayley developmental indices (corrected for gestation) were significantly lower than those of the controls: mental 88±15, mean difference 10 (p<0.02); motor 79±21, mean difference 11 (p<0.05).The results suggest that the complication of IUGR significantly increases the risk of serious sequelae in the tiny premature Infants.

Perinatal Damage to the Developing Brain

Prevention of perinatal damage to the developing brain is a major problem of modern neonatal intensive care. Our approach to this problem in the 1980s is aided by a considerable body of knowledge that has accumulated from diverse investigations over the past 20 years. Follow—up studies have documented the improvements in survival of infants of varying gestational ages and have identified with increasing accuracy those surviving neonates at highest risk of long—term neuro—developmental defects. Correlations between neonatal disease states and outcome have provided information on the relative importance of each neonatal complication in terms of brain damage. Recently, develop—mental neuroanatomy has given much needed information about the vulnerable areas of the neonatal brain at various stages of gestation. Human adult, neonatal, and experimental animal studies have provided additional valuable insights into the pathophysiology of the cerebral lesions seen in neonates. In the last few years, the development of radionucleotide, computed tomography, and ultrasound scans of the brain have enabled localization of at least some neonatal cerebral lesions in the living infant.

1597 DIAGNOSTIC ACCURACY OF NEONATAL BRAIN IMAGING: A POST-MORTEM CORRELATION

During an 11 month period of a prospective study of < 1250 gm appropriate for gestational age infants, 31/87 (36%) died. Autopsies were performed on 24 and revealed 2 (8%) with germinal layer hemorrhage only, 15 (63%) with intraventricular±germinal layer hemorrhage and 7 (29%)without either hemorrhage. During life all infants were scanned through the skull in coronal and axial planes using real-time linear array ultrasound (U/S). Transfontanelle static sector U/S and CT studies were done after death prior to autopsy. The table shows correlation of autopsy findings with these scans.Although the differences are not statistically significant, the results suggest that greatest accuracy is obtained by ultrasound imaging through the fontanelle. It is noteworthy that no method of brain imaging was 100% accurate in detecting hemorrhage.

HEMORRHAGIC AND ISCHEMIC LESIONS IN THE PRETERM BRAIN

During 1 year, 77 infants of gestation < 37 wks survived severe asphyxia, primary apnea or seizures. Sequential brain ultrasound scans were done to determine the incidence and evolution of hemorrhage in the germinal layer (GLH), ventricles (IVH) or cerebral white matter (ICH) and ischemic periventricular leukomalacia (PVL).Groups 1 and 2 (vs 3) had an increased incidence of GLH (p<0.05) and IVH (p<0.01). ICH and major IVH occurred most frequently in Group 1 (vs 2 & 3, p<0.05). PVL diagnosed by white matter echogenicity or cysts occurred with equal frequency across all gestational ages. All cases of IVH and ICH and all but 2 cases of GLH were diagnosed within 14 days of age. PVL superolateral to the ventricle developed later (up to age 67 days) and would have been missed by early scanning. The data suggest that all high risk cases should have additional scans 3 to 6 wks after the insult.

BRONCHIAL HYPERREACTIVITY IN LONG TERM SURVIVORS OF THE NEONATAL RESPIRATORY DISTRESS SYNDROME (RDS)

Recent reports have shown residual bronchial hyperreactivity in long term survivors of bronchopulmonary dysplasia and Wilson Mikity syndromes. Our aim was to extend these studies to survivors of uncomplicated RDS. The study group consisted of 7 males and 7 females born between 1974 and 1976. Measurements of static and dynamic lung volumes were made and a methacholine challenge (MCH) was performed on each child. Expiratory flow rates for the total group were statistically significantly reduced (p < .01). Pulmonary function was significantly lower in the MCH positive group when compared with the MCH negative group. There was a positive correlation between duration of IPPB and log dose MCH, R = -0.78, p = 0.02. There was no significant differences between either group for age, sex, height, weight or age at onset of mechanical ventilation. The MCH positive group had received a significantly longer duration of IPPB during the course of the neonatal respiratory failure. Thus, even in survivors of RDS without major sequelae, there is evidence of residual airway hyperreactivity and abnormal pulmonary function. We consider this increased airway reactivity and reduced pulmonary function to be one of the risk factors in the development of chronic obstructive pulmonary disease later in life.