Mureen Schlueter

Surfactant apoprotein A modifies the inhibitory effect of plasma proteins on surfactant activity in vivo.

ABSTRACT: Surfactant apoprotein A (SP-A) reduces the inhibitory effects of plasma proteins on the surface tension lowering properties of pulmonary surfactant in vitro. To test the effects of SP-A in vivo we administered a complete natural dog lung surfactant (DLS) containing apoproteins SP-A, SP-B, and SP-C, a butanol extract of DLS (DLSE) containing only apoproteins SP-B and SP-C, and DLSE supplemented with SP-A intratracheally to prematurely delivered rabbit pups in the presence of increasing amounts of human plasma. In the absence of plasma DLS and DLSE (100 mg/kg phospholipid) had comparable effects on lung mechanics (compliance during ventilation with a tidal volume of 6–7 mL/kg and quasi-static pressure-volume behavior) in this surfactant deficiency model. Plasma proteins in increasing amounts to a maximum protein concentration of 62.5 mg/mL had no effect on the response of the pups to DLS. In contrast, plasma added to DLSE in concentrations above 20 mg/mL significantly increased the peak inspiratory pressure (PIP) required to ventilate the pups with a tidal volume of 6–7 mL/kg, reduced the calculated total lung compliance, and decreased the deflation lung volumes. The inhibitory effects of plasma on DLSE were significantly less when SP-A was added to DLSE (5:1, phospholipid:SP-A, wt:wt). The addition of SP-A to DLSE in plasma restored the activity of the extract to levels comparable to complete DLS. These results suggest that plasma can interfere with surfactant function and that SP-A has a significant protective effect for surfactant against the inhibitory effects of plasma in vivo.

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

Effects of arterial carbon dioxide tension on the newborn lamb's cardiovascular responses to rapid hemorrhage.

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

Incidence and outcome of a 10-fold indomethacin overdose in premature infants☆☆☆★

450 to

Sleep state and arterial blood gases and pH, in human newborn and young infants

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

RIGHT-TO-LEFT SHUNT THROUGH THE DUCTUS ARTERIOSUS IN NEWBORN INFANTS

71,500. CONCLUSIONS Single-dose rescue surfactant therapy is probably a cost-effective therapy because it produced a lower mortality rate for the same (and probably lower) expenditure. Single-dose prophylactic therapy for smaller infants (< or = 1350 gm) appeared to yield a reduction in mortality rate for a small additional cost. The use of multiple-dose therapy in infants who do not respond to initial therapy may alter the effects described above to either increase or decrease the observed cost-effectiveness of surfactant therapy. Regardless, surfactant therapy will remain a cost-effective method of reducing mortality rates, relative to other commonly used health care interventions.

HOSPITAL COSTS PER SURVIVOR FOR INBORN INFANTS AT 24-26 WEEKS OF GESTATION.• 1443

Summary: Nineteen newborn lambs, spontaneously breathing room air, were hemorrhaged of 50% of their measured blood volume over a 30-min period. They were then observed for the following 90 min. No fluid or blood was reinfused during the study. Eight of the 19 lambs survived beyond the study period, the other 11 died at the end of the hemorrhage or during the recovery period. All lambs became hypotensive and bradycardic during the hemorrhage. All became tachycardic after the hemorrhage. Blood pressure of the survivors returned towards baseline levels whereas it continued to fall in the non-survivors. All animals became anemic, acidotic, and hypocarbic but remained normoxemic.Myocardial blood flow fell to approximately 50% of baseline levels in both survivors and non-survivors during, and at the end of the hemorrhage. It returned to near baseline levels in the survivors by 90 min posthemorrhage. Cerebral blood flow remained at baseline levels during the hemorrhage in the survivors but cerebral oxygen delivery decreased. Flow rose 10% above baseline levels 90 min after hemorrhage but oxygen delivery remained low. In the non-survivors, cerebral blood flow fell to 60% of baseline and cerebral oxygen delivery was 50% of baseline by the end of the hemorrhage.A group of five lambs was hemorrhaged and studied in the same fashion as the 19, except that they breathed 4.5% CO2 beginning 15 min before the hemorrhage, during the hemorrhage and 90 min recovery period. Four of these five survived the study period. They remained normocarbic and became more acidotic than the animals that breathed room air. Blood pressure and heart rate fell during hemorrhage but these decreases were less than in either group of room air breathing animals. During recovery they became tachycardic and blood pressure returned to baseline levels. Myocardial blood flow increased 20% above baseline by the end of hemorrhage and 40% above baseline by 90 min posthemorrhage. Cerebral blood flow increased 40% above baseline during the hemorrhage and remained at that level at the end of hemorrhage and 90 min afterwards. The increase in brain blood flow was sufficient to maintain oxygen delivery to the brain at baseline levels throughout the experiment.Speculation: We speculate that the normal response for the normocarbic lambs is to increase cerebral and myocardial blood flow in response to anemia and hypotension. Spontaneous hyperventilation with hypocarbia tends to interfere with this response both in the brain and in the myocardium. The effect of hypocarbia is greater in the myocardium. The net result is a decrease in oxygen delivery to these tissues. If the same responses were to occur in the human infant it might be important to maintain normocarbia during resuscitation of infants suffering from hemorrhagic shock.

PERINATAL OUTCOME OF INBORN INFANTS BORN AT 24 TO 26 WEEKS GESTATION BETWEEN 1/1990 & 12/1994. † 1312

We reviewed the incidence and morbidity of a 10-fold medication error among all premature infants treated with indomethacin. We detected 4 incidents among 1059 indomethacin doses given to infants weighing less than 1000 g. None of the infants had intracranial hemorrhage, necrotizing enterocolitis, or significant deterioration of renal function.

NEURODEVELOPMENTAL OUTCOME OF PREMATURE INFANTS INBORN AT 24, 25, AND 26 WEEKS GESTATION. † 1636

Sleep state influences the respiratory pattern in adults and infants. Most normal infants between 35 and 46 weeks post-conceptional age have 2 distinct sleep states: Quiet and active. These are analogous to the non-rapid eye movement (NREM) and rapid eye movement (REM) sleep of older subjects. Active sleep is associated with greater respiratory frequency, minute Ventilation [3,8,11, 12] oxygen consumption [18] and frequency of respiratory pauses [3, 5, 6, 7, 10, 20] and with a more irregulär respiratory pattern than quiet sleep. ASERINSKY [2] has shown that in adults there is an association between REM and fall in arterial oxygen Saturation. If this occurred in prematurely born infants it might depress the respiratory center and lead to long periods of apnea and increasing respiratory irregularity [16]. The purpose of this study was to determine whether there was arterial hypoxeniia or hypercarbia associated with active sleep in infants with mild chronic lung dieease.

EFFECT OF ATKOPINE ON THE RESPONSE OF NEWBORN LAMBS TO MASSIVE HEMORRHAGE

In newborn infants if there is a large right-to-left (R-L) shunt through the ductus arteriosus (DA), the oxygen tension (PO2) of umbilical artery (UA) blood could be substantially lower than that going to the head. To explore this, we cannulated a temporal artery (TA) and obtained blood simultaneously from TA and UA for measurement or PO2 (PTAO2 and PUAO2) on 241 occasions in 110 infants (ages 2 hrs to 22 days, birth weights (BW) 510 to 4260 gms) who were breathing O2 concentrations between room air and 100%. Their diagnoses included idiopathic respiratory distress syndrome (90), persistent pulmonary hypertension (4), meconium aspiration (5) and other conditions (11). They were breathing without assistance (WA), with continuous positive airway pressure (CPAP) or were being mechanically ventilated (MV). We calculated R-L shunt using PUAO2 and PTAO2 and estimated R-L through the DA which averaged 2.8% (SD 3.6). PUAO2 was ≤ 80 mmHg in 185 samples and average PTAO2-PUAO2 (T-U) was 3.7 mm Hg (SD 6.2); T-U was ≥20mm Hg in 5 infants who were in profound shock. When PUAO2 was ≥80mm Hg, T-U was 4.3 mm Hg (SD 7.0) for infants ≤ 2000 gms and 2.6mm Hg (SD 4. 1)for those >2000 gms, T-U was 4.2 mm Hg (SD 6.3) for WA, 2.3 mm Hg (SD 3.3) for CPAP and 7.5 mm Hg (SD 10.2) for MV. Clinically important T-U differences are rare regardless of BW or ventilatory status except in severe shock. When PUAO2 is ≤80mm Hg, it can be used safely to approximate the PO2 of blood going to the head.