Anthony Lazzara

Pulmonary effects of furosemide in preterm infants with lung disease

Twenty preterm infants recovering from respiratory distress syndrome at 1 week of age were randomized in this study either to a control or a treatment group. Those treated received a single daily dose of furosemide (1 mg/kg) intravenously. Pulmonary compliance was observed to improve significantly at two hours in the treated group, as compared with that in the controls. The calculated alveolar-arterial oxygen gradient was noted to decrease two hours after furosemide and to remain decreased over the four-day period in the treated group. This improvement in lung function was not secondary to diuresis in the infants treated with furosemide. We conclude that furosemide may have a direct pulmonary effect and improve lung function acutely as well as with chronic administration.

Behavioral and Neurological Characteristics of a Hydranencephalic Infant

A modified Prechtl neurological examination and the Brazelton Neonatal Assessment Scale were serially administered to a hydranencephalic infant over the first eight weeks of life. Clinical, roentgenographic, neurological and behavioral findings are reported. In contrast to earlier reports, visual tracking of a moving field and auditory and visual habituation were observed. Further, in addition to previously reported reflex automatisms, the infant also possessed what are termed ‘socially relevant behavioral automatisms’. The implications of these findings are discussed.

Range-gated pulsed Doppler ultrasonographic evaluation of carotid arterial blood flow in small preterm infants with patent ductus arteriosus

Range-gated pulsed Doppler (RGPD) ultrasonography was utilized to study the effect of a patent ductus arteriosus (PDA) on carotid arterial blood flow in small preterm infants. Carotid arterial flow velocity studies were performed on 23 preterm infants, sampling right and left carotid arteries. Studies on seven infants after PDA ligation and on seven who developed no evidence of PDA were used as controls. A strong relationship was demonstrated between diastolic reversal in the carotid arteries and PDA. The results of this study indicate that the RGPD flow velocity curve from the carotid artery is more sensitive than M-mode echocardiography or clinical examination in detecting PDA, and that PDA in small preterm infants is associated with a distinct abnormality in the carotid arterial flow pattern.

1607 PROSPECTIVE LONG-TERM FOLLOW-UP OF PREMATURES WITH SUBEPENDYMAL/INTRAVENTRICULAR HEMORRHAGE (SEH/IVH)

Since 1977, an ongoing study has assessed neurodevelopmental outcome of CT-documented SEH/IVH in infants <35 weeks gestation requiring intensive care. Scans were graded: normal, SEH, mild, moderate, or marked IVH. Follow-up status, at mean corrected age of 34 months, was assessed by neurologic exams, Bayley and Stanford-Binet tests. Outcome was designated: Good-no neurologic deficit and Developmental Index (D.I.) > 90. Intermediate-no or minor neurologic deficit and D.I. = 70-90: Poor-significant neurologic deficit or D.I.<70. The following groups were compared: a) 33/41 surviving SEH/IVH infants with 30/49 non-IVH; b)22 SEH/IVH infants paired with controls, matched for Apgar, gestation and birth weight c) intragroup, according to degree of hemorrhage. Of the 33 SEH/IVH infants, 21 had good outcomes, 8 intermediate, 4 poor. Of controls, outcome was good in 19, intermediate in 8, poor in 3. Among match-control pairs, there was a balanced distribution in outcome. Intragroup comparison showed: 13 had marked IVH with 8 good outcomes, 3 intermediate, 2 poor; 10 had moderate IVH with 5 good, 3 intermediate, 2 poor, 10 had mild IVH or SEH with 8 good, 2 intermediate, 0 poor. By all methods of comparison, outcome in SEH/IVH infants was not significantly different from controls. Marked IVH did not preclude good outcome (60% good). Other neonatal disease may affect outcome more than hemorrhage.

1384 PULMONARY EFFECTS OF FUROSEMIDE IN PREMATURES WITH LUNG DISEASE

20 consecutive prematures with hyaline membrane disease (HMD) were randomized into 10 controls (CG) and 10 treated patients(TG) at 7 days of age if they still required ventilator assistance or oxygen (F1O2 < 0.21). The TG received a single bolus IV dose of furosemide (F) lmgm/k/day for 4 days and the CG received no diuretic. Mean gestational age of TG was 29 weeks (range 26-31) and of CG was 30 weeks(range 27-36). Birth weight of TG was 1024 gm (range 740-1200) and of CG was 1260gm(range 840-2360). All 20 infants had arterial blood gases and lung compliance (CL) measured at 2 hours, diuresis, natriuresis, F excretion and serum F levels monitored for 6 hours. At 2 hours after F dose, the TG demonstrated improved lung compliance(p <.01). This improvement was not sustained over the 72 hour study period. The mean A-a DO2 in the TG tended to decrease over 2 hours after the F dose(p=0.05) with improvement at 72 hours. Mean urine volume during 6 hours in TG was 33.9±21 ml and in CG was 25.3± 13 ml(p=.35NS). 6 hour sodium excretion was 1.76 mEq(TG) anf 1.45 mEq(CG). There was no correlation between 2 hour serum F levels and 2 hour percent CL change. Urine was collected between time 0-2 hours after F dose. On day 4, the 2 hour CL change correlated with this 2 hour urine volume(r=0.82, p<0.05) the 2 hour urinary sodium(r=0.94, < 0.05) and the 2 hour urine F(p=0.07). Despite poor renal clearance of F the pulmonary effects are related to its diuretic effect. The lack of sustained pulmonary effect is explained by the brief diuresis.

Resuscitation of the newborn

Effective resuscitation of the newborn requires knowledge of the cause of depression. Four major causes are trauma, asphyxia, medication, and malformation. More than one of these may contribute to depression in a single infant. The first principles of resuscitation are to avoid cooling the infant and to establish an airway. Infants with an Apgar score of 3 to 4 at one minute usually need bag-and-mask ventilation, while those with scores of 0 to 2 require immediate ventilation, preferably by means of endotracheal intubation. Severely depressed infants may also require chemical resuscitation and closed cardiac massage. Fetal depression caused by narcotic analgesics given to the mother can be reversed with the use of naloxone hydrochloride (Narcan). Infants asphyxiated on the basis of malformations may benefit from expeditious diagnostic and therapeutic procedures performed in the delivery room.

1571 DETECTION OF INTRACRANIAL CALCIFICATIONS IN NEONATES WITH CRANIAL ULTRASONOGRAPHY

Intracranial calcifications comprise one of the hallmarks of congenital intrauterine infection. Rapid detection of such lesions could lead to earlier documentation of diagnosis with appropriate isolation, evaluation and treatment.In a series of nine infants with signs and symptoms of congenital intrauterine infection and/or microcephaly, bedside cranial ultrasonography was performed prior to routine skull radiograph and CT brain scan with a linear array B-mode scanner. Presence of intraparenchymal and periventricular calcification ascertained by ultrasound in all nine infants was corroborated by CT brain scan. Skull x-rays were interpreted as normal in 3/5 infants.Cranial ultrasound provides a sensitive reliable bedside alternative to x-ray studies for diagnosis of intracranial calcifications in newborns.

1588 PROGRESSIVE POSTHEMORRHAGIC HYDROCEPHALUS: FACTORS PREDICTING RESPONSE TO LUMBAR PUNCTURE MANAGEMENT

Eighteen preterm infants with severe progressive post-hemorrhagic hydrocephalus (PPH) following IVH were managed with serial lumbar punctures (LP) according to the following protocol. Daily serial LP with measurement of opening and closing pressure (OP,CP) were performed for no more than four weeks. Sufficient CSF was removed with each LP to lower OP by half. If OP became normal (≤ 80 mm H2O) and remained so for two successive days, LP was deferred for 48 hours and then repeated. If OP remained ≤ 80 mm H2O LP management was discontinued and the patient observed. If hydrocephalus progressed after discontinuation of LP or symptoms of increased intracranial pressure developed during LP management, shunt was effected.Of the 18 infants thus far studied, 11 responded to LP management. OP in 10 of the 11 was ≤ 80 mm H2O by three weeks; none of the non-responders demonstrated OP ≤ 80 mm H2O prior to three weeks of therapy (p=0.0002). Initial CSF protein and sugar and response of CSF protein and sugar to LP were not predictive of response.In conclusion, attainment of OP of ≤ 80 mm H2O for 3 successive days within a 21 day period of serial LP management is highly predictive of PPH response to LP management.

351 FUROSEMIDE PHARMACOKINETICS AND DRUG RENAL EXCRETION IN PREMATURE INFANTS ON CHRONIC THERAPY

During the treatment of 12 normally hydrated prematures with furosemide (F) for chronic lung disease (BPD) F serum levels and urine excretion were measured using gas chromatography. Six hours post drug administration the diuretic responsewas monitored in treated group (TG) and compared to the control group (CG) of 10 premature infants. The mean gestational age of TG was 29 weeks (range 26-31) and of CG was 30 weeks (range 27-36). The TG received a single bolus IV dose of F (1mgm/kg/day) daily for 4 to 7 days. Eight patients entered the study on day 7, and 4 patients were 9-11 days old on entry. Duration of the study was 4-7 days. The mean renal clearance of F on day 1(D1) of the study was 0.04 cc/min (range 0.003cc/min to 0.13cc/min). The mean renal clearance after 4(D4) or 7(D7) days of therapy was 0.05cc/min (range 0.003cc/min to 0.12cc/min). On D1 mean serum F levels were 4.6 ugm/m1 at 2 hours and 3.66 ugm/m1 at 6 hours after F. On D4 and D7 the mean serum levels were 10.33 ugm/m1 (2 hrs) and 6.67 ugm/m1 (6 hrs). This is a significant increase in mean serum levels (P ≤ .01) from first day of treatment. 6 hour plasma half life (T½) in these patients changed from mean of 5.2 hours (D1) to 10 hours (D4 or D7). In 2 patients mean T½ over 12 to 24 hours was 7.15 hours (D1) and increased to 26.15 hours. Mean urine volume during 6 hours in TG was 33.9+21 ml and in CG was 25.3±13 m1 (p=.35NS). Six hour sodium excretion was 1.76 mEq (TG) and 1.45 mEq (CG). During daily F administration, there is serum drug accumulation due to the very low renal clearance.

1293 INTRAVENTRICULAR HEMORRHAGE AND THE PRETERM SGA NEWBORN

151 consecutive newborn infants < 35 weeks gestation requiring intensive care for more than 24 hours were studied regarding occurrence of subependymal and/or intraventricular hemorrhage(SEH/IVH) with CT scans, ventricular tap or autopsy in 1977 and 1978. SEH/IVH occurred more frequently in the SGA group (36/71) than in the AGA group (28/80). 22/42 SGA infants and 26/61 AGA infants with hyaline membrane disease (HMD) had SEH/IVH. Factors significantly related (p < 0.02) to SEH/IVH in AGA infants were alveolar rupture, bicarbonate administration after 1st 24 hours, mechanical ventilation, PCO2 > 50, peak inflation pressure >25 cm H2O and 1:E ratio > 1:1. The only factor significantly related to SEH/IVH in SGA infants was the occurrence of alveolar rupture. 14/20 AGA infants and 16/20 SGA infants with alveolar rupture had SEH/IVH. SGA infants appear to be at higher risk of SEH/IVH than AGA infants. The occurrence of SEH/IVH in the preterm SGA infant may be on a different basis than in the AGA infant and related to prenatal nutritional status rather than postnatal iatrogenic events. Prenatal or intrapartum events superimposed upon decreased supportive tissue in the germinal matrix of the SGA infant may play an important role in the evolution of SEH/IVH in the preterm SGA infant.