Roderic H. Phibbs

Treatment of the Idiopathic Respiratory-Distress Syndrome with Continuous Positive Airway Pressure

Abstract We applied a continuous positive airway pressure to 20 infants (birth weight 930 to 3800 g) severely ill with the idiopathic respiratory-distress syndrome. They breathed spontaneously. Pressure, up to 12 mm of mercury, was delivered through an endotracheal tube to 18 infants and via a pressure chamber around the infants head to two. Arterial oxygen tension rose in all, permitting us to lower the inspired oxygen an average of 37.5 per cent within 12 hours. Minute ventilation decreased with increased continuous positive airway pressure, but this had little effect on arterial carbon dioxide tension, pH, arterial blood pressure and lung compliance. Sixteen infants survived, including seven of 10 weighing less than 1500 g at birth.

Persistent pulmonary hypertension of the newborn infant

Persistent pulmonary hypertension of the newborn infant can be difficult to distinguish from other cardiopulmonary causes of cyanosis during the newborn period. Infants with PPHN have cyanosis, tachypnea, acidemia, normal pulmonary parenchymal markings on the chest radiography, and anatomically normal hearts. We have identified and treated 11 infants and have noted several signs and symptoms not previously emphasized. These are cineangiocardiographic evidence of atrioventricular valve insufficiency in association with systolic murmurs and slow ventricular emptying, apnea, hypocalcemia, only a small rise in abdominal aortic blood oxygen tension during breathing of 100% oxygen, and no response to continuous positive airway pressure. Right-to-left shunting through the patent ductus arteriosus was documented in nine infants: in all six of those in whom simultaneous temporal and abdominal aortic blood oxygen tension measurements were made; in three by means of cardiac catheterization. Ten infants survived after variable courses and treatments which makes it difficult to ascribe improvement to any one therapy. The distinct increase in blood oxygen tension with tolazoline HCl and curare in some instances is discussed.

Recombinant human erythropoietin in the anemia of prematurity: Results of a placebo-controlled pilot study

Experimental and clinical data implicate inadequate erythropoietin production as an important reason that infants acquire this anemia and suggest that recombinant human erythropoietin (r-HuEPO) might be used to treat or prevent it. We therefore randomly assigned 20 small premature infants (birth weight less than or equal to 1250 gm) who were highly likely to require erythrocyte transfusions for anemia of prematurity to receive 6 weeks of treatment with either intravenously administered r-HuEPO (at a dose of 100 units/kg twice each week) or a placebo. Hematologic measurements, transfusion requirements, and growth were followed during therapy and for 6 months thereafter. Treated (EPO) and control babies did not differ with respect to weight, hematocrit, overall mean absolute reticulocyte count, calculated erythrocyte mass, or rate of growth. However, reticulocyte counts increased earlier in patients given r-HuEPO. Six of ten babies in the EPO group, and 8 of 10 assigned to the control group, received at least one erythrocyte transfusion during treatment. For all infants the amount of blood sampled for laboratory tests was strongly predictive of the volume of packed erythrocytes transfused (r = 0.890; p = 0.0001). Of nine infants who had less than 20 ml packed erythrocytes removed for laboratory tests, none of four given r-HuEPO received a transfusion, whereas three of five infants assigned to the placebo group received one. No toxic effects were attributable to r-HuEPO, and no significant changes in leukocyte or platelet counts occurred during treatment. Reticulocyte counts were correlated with simultaneous platelet counts and were inversely related to absolute neutrophil counts in both study groups. We conclude that r-HuEPO administration is safe and feasible at the dose studied. Additional controlled trials utilizing higher doses of r-HuEPO and larger numbers of patients are justified.

Postnatal changes in erythropoietin levels in untransfused premature infants

The purpose of this study was to determine whether an inappropriately low erythropoietin response in premature infants might be a basis for the anemia of prematurity. Erythropoietin was measured by radioimmunoassay in conjunction with hemoglobin and reticulocyte count in untransfused premature infants between birth and 60 days of age. The 27 infants had a mean gestational age of 31 weeks and a mean birth weight of 1378 gm. Between 2 and 30 days, mean erythropoietin concentration was 9.7 mU/ml, significantly and substantially lower than 15.2 mU/ml in 15 concurrently studied healthy adults (P less than 0.01). Subsequently, from 30 to 60 days, values rose gradually to a mean of 17.2 mU/ml, which did not differ significantly from the mean value in adults. Hemoglobin values fell from a mean of 12.9 gm/dl during the first month to 9.0 gm/dl between 30 and 60 days. Thus, during the second postnatal month, preterm infants had essentially the same erythropoietin values as in adults despite a mean hemoglobin concentration that averaged less than two thirds the adult value. This failure to mount a greater erythropoietin response may help to explain why hemoglobin declines to such low values at 2 months of age.

Enhancement of erythropoiesis by recombinant human erythropoietin in low birth weight infants: a pilot study.

We randomly assigned eight concurrently symptom-free premature infants (birth weight less than or equal to 1250 gm) at high risk of requiring erythrocyte transfusions for anemia of prematurity to 6 weeks of intensive treatment with either subcutaneous recombinant human erythropoietin (r-HuEPO group) or a placebo (control group). Treatment with r-HuEPO was initiated at a dose of 100 units/kg per day 5 days a week, and was increased to 200 units/kg per day after 2 or 3 weeks if target reticulocyte counts were not achieved. All patients were given supplemental oral iron therapy at a dose of 6 mg/kg per day, as tolerated. Mean reticulocyte counts in r-HuEPO-treated and control infants were 64,600 versus 67,500 cells/mm3 at entry; were 245,600 versus 78,000 cells/mm3 after 1 week; and averaged 262,600 versus 136,400 cells/mm3 during the study. Mean reticulocyte counts in r-HuEPO-treated infants were 251,200 cells/mm3 during the week when r-HuEPO, 100 units/kg per day, was given, and were 269,500 cells/mm3 after the dose was increased to 200 units/kg per day. Mean hematocrit values at entry were 33.4% in babies who received r-HuEPO versus 33.6% in the control subjects, and were 31.4% in r-HuEPO-treated and 25.2% in the control subjects at the end of treatment. One r-HuEPO-treated and three control babies received transfusions during the study; the total volume of blood given was 17 ml in the r-HuEPO group and 101 ml in the control subjects. The percentage of hemoglobin F increased in infants not given transfusions. We conclude that r-HuEPO stimulates endogenous erythropoiesis in small premature babies who are receiving supplemental oral iron therapy. A controlled multicenter trial has been undertaken to confirm these promising preliminary observations.

Cesarean delivery rates and Neonatal morbidity in a low-risk population

OBJECTIVE: To estimate the relationship between case-mix adjusted cesarean delivery rates and neonatal morbidity and mortality in infants born to low-risk mothers. METHODS: This retrospective cohort study used vital and administrative data for 748,604 California singletons born without congenital abnormalities in 1998–2000. A total of 282 institutions was classified as average-, low-, or high-cesarean delivery hospitals based on their cesarean delivery rate for mothers without a previous cesarean delivery, in labor at term, with no evidence of maternal, fetal, or placental complications. Neonatal mortality, diagnoses, and therapeutic interventions determined by International Classification of Diseases, 9th Revision, Clinical Modification codes, and neonatal length of stay were compared across these hospital groupings. RESULTS: Compared with average-cesarean delivery-rate hospitals, infants born to low-risk mothers at low-cesarean delivery hospitals had increased fetal hemorrhage, birth asphyxia, meconium aspiration syndrome, feeding problems, and electrolyte abnormalities (P < .02). Infused medication, pressors, transfusion for shock, mechanical ventilation, and length of stay were also increased (P < .001). This suggests that some infants born in low-cesarean delivery hospitals might have benefited from cesarean delivery. Infants delivered at high-cesarean delivery hospitals demonstrated increased fetal hemorrhage, asphyxia, birth trauma, electrolyte abnormalities, and use of mechanical ventilation (P < .001), suggesting that high cesarean delivery rates themselves are not protective. CONCLUSION: Neonatal morbidity is increased in infants born to low-risk women who deliver at both low- and high-cesarean delivery-rate hospitals. The quality of perinatal care should be assessed in these outlier hospitals. LEVEL OF EVIDENCE: III

Cost effects of surfactant therapy for neonatal respiratory distress syndrome

OBJECTIVE To examine the cost effects of a single dose (5 ml/kg) of a protein-free synthetic surfactant (Exosurf) as therapy for neonatal respiratory distress syndrome, for both rescue and prophylactic therapy. RESEARCH DESIGN Nonblinded, randomized clinical trials of both rescue and prophylactic therapy. Regression analyses were used to control for the independent effects of sex, multiple birth, delivery method, birth weight, and surfactant therapy. SETTING The prophylactic trial was conducted at a university medical center only; the rescue trial also included a tertiary community hospital. PATIENTS Prophylaxis was administered immediately after birth to 36 infants (38 control subjects) with birth weights between 700 and 1350 gm. Rescue therapy was administered at 4 to 24 hours of age to 53 infants (51 control subjects) with established respiratory distress syndrome and birth weights > or = 650 gm (no upper limit). Infants in the prophylactic trial were not eligible for the rescue trial. RESULTS For the rescue trial, there was a

Age-related differences in erythropoietic response to recombinant human erythropoietin: comparison in adult and infant rhesus monkeys.

16,600 reduction in average hospital costs (p = 0.18), which was larger than the cost of the surfactant (

Continuous positive airway pressure and pulmonary and circulatory function after cardiac surgery in infants less than three months of age.

450 to

Plasma Thyroid Hormones in Premature Infants: Effect of Gestational Age and Antenatal Thyrotropin-Releasing Hormone Treatment

900), yielding a probable net savings. For the prophylactic trial, hospital costs were larger for treated infants versus control subjects who weighed less than about 1100 gm at birth and lower for treated infants versus control subjects who weighed more than 1100 gm at birth (p < 0.05). For the prophylactic sample, the result was an average cost per life saved of