Metabolic response of preterm infants to variable degrees of respiratory illness.

In older children and adults, physiologic instability associated with severe illness causes increased cellular oxygen consumption (VO2), increased serum lactate and cortisol levels, and more negative nitrogen balance. To determine the metabolic response of preterm infants to severity of respiratory illness, we analyzed VO2, nitrogen balance, urinary 3-methyl-histidine and norepinephrine concentrations, and serum levels of lactate and cortisol as a function of ventilatory index (VI). Twelve 2-day-old premature infants who were appropriate in size for gestational age (mean +/- SEM birth weight: 1460 +/- 251 gm) and who required mechanical ventilation for respiratory distress syndrome had VO2 and carbon dioxide production measured by indirect calorimetry and blood and urine samples obtained concurrently. All infants received amino acids, 1.0 gm/kg per day, and a mean energy intake of 27 +/- 3 kcal/kg per day, provided as a parenteral dextrose solution. The resting energy expenditure exceeded energy intake in all infants. The VO2 value ranged from 5.5 to 9.2 ml/kg per minute and was directly correlated with VI (r = 0.79; p = 0.002). Nitrogen balance ranged from -160 to 53 mg/kg per day (mean: -33 +/- 21 mg/kg per day) but was not dependent on VI (r = 0.04) or VO2 (r = 0.01). The serum lactate level correlated directly with VI (r = 0.82; p = 0.002) and VO2 (r = 0.60; p = 0.05), but cortisol and urinary norepinephrine levels did not. We conclude that preterm infants with respiratory distress syndrome have increased VO2 rates and serum lactate concentrations directly related to the degree of respiratory illness. They are generally in a state of mildly negative nitrogen balance, the degree of which is not related to severity of illness. Although these infants may require increased energy delivery during illness, they do not appear to require excessive amounts of amino acids.

Effect of spontaneous and mechanical breathing on dynamic lung mechanics in hyaline membrane disease.

We measured then compared the dynamic lung mechanics of spontaneous breaths and mechanical breaths in 9 mechanically ventilated neonates with hyaline membrane disease. All were receiving intermittent mandatory ventilation. All breathed spontaneously between ventilator breaths. Tidal volume, transpulmonary pressure, dynamic lung compliance, airways resistance, and peak inspiratory and peak expiratory gas flows were determined for both the mechanical and the spontaneous breaths. The mechanical breaths consistently had larger tidal volumes, higher transpulmonary pressures, higher airway resistance, and lower lung compliance values (P less than 0.05). Peak inspiratory and expiratory gas flows were also higher (P less than 0.01) during mechanical breathing. The spontaneous breaths generated by patients and the mechanical breaths generated by mechanical ventilators are different. The lung mechanics measurements of these two different types of breathing should be collected, analyzed, and reported separately.

Transvascular flux and tissue accrual of Evans blue: effects of endotoxin and histamine.

We investigated the relationship between the pharmacokinetics of exogenous molecules and transcapillary flux by studying the intravascular and tissue content and the histologic distribution of Evans blue in guinea pigs. Pharmacokinetic analysis demonstrated that 87% of the decline in intravascular Evans blue during the first 3 hours after administration was a result of transvascular flux to tissue compartments. Rapidly and slowly equilibrating compartments were identified. Greater than 90% of the clearances in lung and heart were rapid compartment clearances. Histologically, the distribution of Evans blue in these tissues was predominantly extracellular and similar to the distribution of fluorescein-labeled dextran. By contrast, the accumulation in kidney and liver was kinetically similar to characteristics of the slowly equilibrating compartment. This corresponded histologically to the predominant intracellular uptake of Evans blue in these tissues. Generalized increases in capillary permeability were produced by endotoxin or histamine infusion. Both treatments were associated with a more rapid initial decline in intravascular content of Evans blue than was found in control animals. Although the histologic distribution of Evans blue in tissues was not altered, endotoxin was associated with a more rapid appearance of Evans blue in the lung and heart than was seen in controls. We conclude that the initial decline in intravascular content of Evans blue corresponds to the intercompartmental clearance and to transcapillary macromolecular flux. The initial decline in serum concentrations may therefore be useful in studying disorders of generalized capillary permeability. Furthermore, the initial accrual of Evans blue in the lung and heart may be used as a marker of transcapillary macromolecular flux in those tissues.