George A. Gregory

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.

The independent effects of hyperventilation, tolazoline, and dopamine on infants with persistent pulmonary hypertension

We studied the separate and combined effects of hyperventilation and administration of dopamine and tolazoline in five infants with pulmonary hypertension managed with indwelling pulmonary artery catheters. In five infants the right-to-left shunt reversed during ventilator-induced respiratory alkalosis (pH greater than 7.6). Response to drugs was variable and unpredictable. One infant could be oxygenated at normal pH during combined dopamine and tolazoline infusion. Other infants showed no response to drugs, or became worse during infusion. The ratio of pulmonary artery to systemic artery pressure averaged 1.14 with standard therapy, but decreased to 0.98 following respiratory alkalosis alone, to 0.87 following drug infusions, and to 0.70 following the combination of alkalosis and drug infusion. These changes were significant by analysis of variance at P less than 0.02, P less 0.001, and P less than 0.001, respectively. Systemic oxygenation was satisfactory in all cases when the pulmonary to systemic pressure ratio was less than 1.0.

The Relationship between Age and Halothane Requirement in Man

The minimum alveolar concentration (MAC) values for halothane in eight age groups were determined. MAC was found to be highest in newborns and lowest in the elderly. These changes in anesthetic requirement with age parallel changes in cerebral oxygen consumption, cerebral blood flow and neuronal density.

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.

Patent ductus arteriosus in premature infants.

Abstract Patent ductus arteriosus (PDA) developed in 17 of 111 premature infants (birth weight 1750 g or less) born during a four-year period (15.3 per cent incidence). During that time we treated 29 such infants, 17 born at our own institution and 12 similar infants transferred from other hospitals. Sixteen of the 29 had cardiac catheterization, 10 had operative closure of the PDA, and 24 survived. When the PDA became evident, 23 infants had no pulmonary disease, were recovering from the idiopathic respiratory-distress syndrome (IRDS) or had chronic lung disease; all survived. In six infants with severe IRDS, onset of PDA was associated with a worsening of the pulmonary status; only one survived. We recommend cardiac catheterization and operative closure of the PDA in neonates when heart failure cannot be controlled medically. The prognosis is good in infants in whom onset of PDA is not associated with progressively worsening IRDS.

Hypoxia-Induced Dysfunctions and Injury of Astrocytes in Primary Cell Cultures

The effects of severe hypoxia were studied in a primary culture of astrocytes prepared from newborn rat cerebral cortex. Hypoxia was created by placing cultures in an airtight chamber that was flushed with 95% N2/5% CO2 for 15 min before being sealed. The hypoxic environment was maintained constant for up to 24 h. During the first 12 h of hypoxia, astrocytes showed no morphological changes by phase-contrast microscopy. After 18 h of hypoxia, some astrocytes in culture became swollen and started to detach from the culture dish. All cells in the culture were destroyed after 24 h of hypoxia. The lactate dehydrogenase level in the culture medium increased more than tenfold between 12 and 24 h of hypoxia. Glutamate uptake was inhibited 80% by similar hypoxic conditions. The cell volume of astrocytes, as measured by 3-O-methyl-[14C]-D-glucose uptake, was increased. These observations suggested cell membrane dysfunction. The malondialdehyde level of hypoxic cultures increased twofold after 24 h of hypoxia. Verapamil (0.5 mM), furosemide (1 mM), indomethacin (1 mM), MgCl2 (10 mM), and mannitol (10 mM) reduced but never completely abolished the release of lactate dehydrogenase from hypoxic astrocytes. These data suggest multifactorial causes for severe injury in hypoxic astrocytes.

Pharmacokinetics and Pharmacodynamics of d-Tubocurarine in Infants, Children, and Adults

&NA; The pharmacokinetics and pharmacodynamics of d‐tubocurarine (dTc) were determined in neonates (0–2 months, n = 7), infants (212 months, a = 7), children (1–12 years, n = 9), and adults (12–30 years, n = 8) during 70% nitrous oxide, 0.58 MAC halothane anesthesia. dTc was administered by infusion, while blood for determination of plasma dTc concentrations was obtained, and the EMG of the adductor pollicis recorded. The plasma dTc concentration at which 50% depression of EMG twitch height occurs (Cpss(50)) was 0.18 ± 0.09 &mgr;g/ml in neonates, and 0.27 ± 0.06 &mgr;g/ml in infants, both significantly lower than the values of 0.42 ± 0.14 and 0.53 ± 0.14 &mgr;g/ml for children and adults, respectively. The steady‐state distribution volume (Vdss) was 0.74 ± 0.33 l/kg in neonates, significantly greater than the values of 0.52 ± 0.22, 0.41 ± 0.12, and 0.30 ± 0.10 1/kg in infants, children, and adults, respectively. The elimination half‐life (t&bgr;1/2) was 174 ± 60 min in neonates, significantly longer than the values of 90 ± 23 and 89 ± 18 min in children and adults, respectively. Plasma clearance did not differ with age. We also determined D50, the product of Vdss and Cpss(50). D50, the quantity of drug present at steady‐state to produce 50% paralysis, did not differ between groups. The authors conclude that during comparable nitrous oxide‐halothane anesthesia, neonates and infants have an increased sensitivity to dTc, as determined by Cpss(50). However, because of he larger Vdss in younger patients, dose size should not differ with age. In addition, because of the longer t&bgr;1/2 in neonates, second and subsequent doses should be required at less frequent intervals.

Anesthetic Requirements for Halothane in Young Children 0–1 Month and 1–6 Months of Age

In a previous study, the authors found that infants, in the first 6 months of life, required the highest minimum alveolar concentration (MAC) of any age group (1.09% halothane). Because only two neonates (0-31 days of age) were included in the original study and because profound depression of blood pressure and heart rate have been reported in neonates, the authors determined 1) whether the MAC of halothane in neonates (n = 12) differs from that in infants (1-6 months of age) (n = 12) and 2) whether the blood pressure and heart rate responses in neonates differ from those in infants at approximately 1 MAC. The authors found that the MAC of halothane in neonates, 0.87% +/- 0.03 SEM, was significantly lower (P less than 0.01) than that in infants, 1.20% +/- 0.06 SEM. With induction of anesthesia, the systolic blood pressure decreased 23% in neonates (P less than 0.05) and 34% in infants (P less than 0.005) from awake values. Similarly, the heart rate decreased 12% in neonates and 22% in infants (P less than 0.05). The incidence of hypotension (greater than 30% decrease in systolic blood pressure from awake) in neonates, 33%, was not significantly different from that in infants, 44%. The authors conclude that the MAC of halothane in neonates is 25% less than that in infants and significantly less than was thought previously. The MAC in infants is the highest of any age group. The decrease in blood pressure and the incidence of hypotension in neonates are similar to those in infants at approximately 1 MAC of halothane.

Fentanyl-air-oxygen anesthesia for ligation of patent ductus arteriosus in preterm infants.

In 10 premature infants (1123 ± 263 g), fentanyl citrate (30 to 50 μg/kg) was used in conjunction with pancuronium (0.1 mg/kg) as the sole anesthetic for transthoracic ligation of patent ductus arteriosus. Ventilation was controlled with air and oxygen in concentrations sufficient to maintain transcutaneous Po2 between 50 and 70 torr. Circulatory stability was easily maintained throughout the procedure. “Stiff chest” was avoided by the use of muscle relaxants, and the infants were awake within 1 hour after the procedure.

Evolution of Brain Injury After Transient Middle Cerebral Artery Occlusion in Neonatal Rats

BACKGROUND AND PURPOSE Stroke in preterm and term babies is common and results in significant morbidity. The vulnerability and pathophysiological mechanisms of neonatal cerebral ischemia-reperfusion may differ from those in the mature cerebral nervous system because of the immaturity of many receptor systems and differences in metabolism in neonatal brain. This study details the neuropathological sequelae of reperfusion-induced brain injury after transient middle cerebral artery (MCA) occlusion in the postnatal day 7 (P7) rat. METHODS P7 rats were subjected to 3 hours of MCA occlusion followed by reperfusion or sham surgery. Diffusion-weighted MRI was performed during MCA occlusion, and maps of the apparent diffusion coefficient (ADC) were constructed. Contrast-enhanced MRI was performed in a subset of animals before and 20 minutes after reperfusion. Triphenyltetrazolium chloride (TTC) staining of the brain was performed 24 hours after reperfusion. Immunohistochemistry to identify astrocytes (glial fibrillary acidic protein), reactive microglia (ED-1), and neurons (microtubule-associated protein 2) and cresyl violet staining were done 4, 8, 24, and 72 hours after reperfusion. RESULTS On contrast-enhanced MRI, nearly complete disruption of cerebral blood flow was evident in the vascular territory of the MCA during occlusion. Partial restoration of blood flow occurred after removal of the suture. A significant decrease of the ADC, indicative of early cytotoxic edema, occurred in anatomic regions with a disrupted blood supply. The decline in ADC was associated with TTC- and cresyl violet-determined brain injury in these regions 24 hours later. The ischemic core was rapidly infiltrated with reactive microglia and was surrounded by reactive astroglia. CONCLUSIONS In P7 rats, transient MCA occlusion causes acute cytotoxic edema and severe unilateral brain injury. The presence of a prominent inflammatory response suggests that both the ischemic episode and the reperfusion contribute to the neuropathological outcome.