Indomethacin inhibition of intralipid-induced lung dysfunction.

Intralipid-related pulmonary alterations have been attributed to hyperlipemia. To better quantitate and explain these alterations, Intralipid (0.4 gm/kg over one hour) was infused into three groups of rabbits and saline into a fourth group. Group I had normal lung function; Groups II-IV were pretreated with oleic acid and Group III also received indomethacin. Serum triglyceride (TG) levels, arterial (a) and end-tidal (A) PCO2 and PO2 were measured at baseline and then hourly for six hours. There was no ventilatory deterioration in Group I despite a peak TG level of 638 mg/dl. In Group II there was an Intralipid-related PaO2 decrease of 11-13 mmHg (p less than .01) and a delta AaPO2 increase of 16 mmHg (p less than .01); both returned to baseline without significant TG normalization. Since indomethacin prevented these PaO2 and delta AaPO2 changes despite a significant TG increase, the effects of Intralipid appear not to be TG-related but rather to be related to PG-mediated alterations in pulmonary vasomotor tone. Our results are most consistent with a net increase in vasodilating prostaglandins and resultant hypoxemia secondary to unblocking of baseline hypoxic vasoconstriction.

Laboratory monitoring of parenteral nutrition-associated hepatic dysfunction in infants.

Hepatic dysfunction associated with parenteral nutrition (PN) is a well recognized occurrence. In order to define the temporal inter-relationships of direct bilirubin to other laboratory parameters, total and direct bilirubin, serum glutamic-pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), and alkaline phosphatase were measured prior to beginning PN and then weekly throughout the duration of PN in 60 consecutive neonates. Cholestatic jaundice (ChJ), defined as a direct bilirubin greater than or equal to 2.0 mg/dl, developed in 11 (33%) of 33 infants receiving PN for at least 2 weeks. Direct bilirubin was the most sensitive and earliest indicator of ChJ. SGOT and SGPT values in the ChJ group were not statistically different from the non-ChJ group until 2 weeks after the onset of cholestasis. Although there was a progressive increase in alkaline phosphatase during the course of PN, the increase was not greater in the ChJ group. In summary, direct bilirubin is the only laboratory indicator of hepatic status that need be determined serially in parenterally alimented infants. Although SGPT and SGOT may be helpful in characterizing hepatic dysfunction once ChJ has occurred, alkaline phosphatase levels do not reliably assess PN-associated liver injury.

Prospective controlled study of parenteral nutrition-associated cholestatic jaundice: effect of protein intake.

The development of transient cholestatic jaundice is a well-recognized complication of prolonged parenteral nutrition. The etiology and long-term significance have not been established. This report describes a prospective controlled study designed to compare the hepatic effects of two different parenteral protein intakes, a lower protein regimen of 2.3 gm/kg/day and a higher protein regimen of 3.6 gm/kg/day. The minimum criterion for ChJ was a direct bilrubin greater than or equal to 2.0 mg/dl. Eighty-two consecutive infants completed the study. No ChJ occurred in the 39 infants who received PN for less than two weeks. In 43 infants requiring PN for at least two weeks, the incidence of ChJ was similar in the two groups, six infants in the LP and seven in the HP group. However, infants prospectively assigned to the HP group developed ChJ earlier than the LP group, 27 +/- 6 days (P less than 0.01), and achieved a significantly greater peak direct bilrubin level, 8.4 +/- 1.6 versus 3.2 +/- 0.3 mg/dl (P less than 0.001). Retrospective comparison of the 13 ChJ infants to the 30 long-term PN infants without ChJ revealed a significantly greater daily dextrose intake in those developing ChJ, 16.2 +/- 1.1 gm/kg/day versus 13.4 +/- 0.9 in the group without ChJ (P = 0.025). Our results indicate that an increased parenteral protein intake is associated with an earlier and increased magnitude of ChJ and suggest than an increased dextrose intake may be associated with an increased frequency of ChJ.

The effect of overdistention of the lung on pulmonary function in beagle puppies.

The removal of one lung from a beagle puppy results in minimal interference with lung function or the arterial gases. The removal of air from the empty pleural cavity results in a shift of the mediastinum and overdistention of the contralateral lung. An immediate decrease in the PO2 and increase in the PCO2 is seen. Significant increase in the alveolar-arterial CO2 gradient reflected marked increase in dead space ventilation. Biopsies of the overdistended lung demonstrated emphysema and disruption of alveoli. These changes may explain some of the deterioration of lung function and the complication of contralateral pneumothorax following repair of a Bochdalek diaphragmatic hernia. Our study suggests that the mediastinum should be stabilized in the midline after repair of a diaphragmatic hernia or after a pneumonectomy in an infant or small child.

Respiratory and nonrespiratory effects of doxapram in congenital central hypoventilation syndrome.

Doxapram is a respiratory stimulating drug that affects both peripheral chemoreceptors and medullary respiratory and nonrespiratory neurons. We administered doxapram 60 2 infants with congenital central hypoventilation syndrome. In 6 separate trials at a dose range of 0.32 to 2.0 mg per kg of body weight per min, quiet-sleep tidal volume increased from 4.9 +/- 1.0 to 8.5 +/- 0.9 ml per kg of body weight, minute ventilation increased from 140 +/- 38 to 286 +/- 31 ml per kg of body weight per min, and alveolar PCO2 decreased from 60 +/- 5 to 32 +/- 2 mm Hg. In all instances, the maximal quiet-sleep ventilatory response was achieved within 10 min. The ventilatory response to steady-state CO2 breathing was not improved with doxapram. A continuous infusion of doxapram for 5.2 days in one infant successfully maintained normal quiet-sleep ventilation. In both infants, multiple nonrespiratory effects of doxapram occurred; enteral administration was associated only with generalized neuromuscular stimulation, but the 5-day intravenous infusion was also associated with acute hepatotoxicity and a perforated duodenal ulcer. The medullary respiratory neurons in central hypoventilation syndrome may be incapable of responding to doxapram, and the ventilatory responses observed may be due entirely to stimulation of peripheral chemoreceptors. Although quiet-sleep ventilation can be successfully maintained with intravenous and enteral administration of doxapram, and tachyphylaxis has not been observed, we have been unable to avoid at least the neuromuscular manifestations of nonrespiratory medullary stimulation.