David W. Smith

Ventilatory mechanisms of exercise intolerance in chronic heart failure

Mechanisms that have been suggested to underlie the abnormal ventilatory response to exercise in patients with chronic congestive heart failure (CHF) include high pulmonary pressures, ventilation-perfusion mismatching, early metabolic acidosis, and abnormal respiratory control. To evaluate the role that ventilation and gas exchange play in limiting exercise capacity in patients with CHF, data from 33 patients with CHF and 34 normal subjects of similar age who underwent maximal exercise testing were analyzed. Maximal oxygen uptake was higher among normal subjects (31.7 +/- 6 ml/kg/min) than among patients with CHF (17.7 +/- 4 ml/kg/min; p less than 0.001). The ventilatory equivalent for oxygen, expressed as a percentage of maximal oxygen uptake, was 25% to 35% higher among patients with CHF compared with normal subjects throughout exercise (p less than 0.01). A steeper component effect of ventilation on maximal oxygen uptake was observed among normal subjects compared with patients with CHF, which suggests that a significant portion of ventilation in CHF is wasted. Maximal oxygen uptake was inversely related to the ratio of maximal estimated ventilatory dead space to maximal tidal volume (VD/VT) in both groups (r = -0.73, p less than 0.001). Any given oxygen uptake at high levels of exercise among patients with CHF was accompanied by a higher VD/VT, lower tidal volume, and higher respiratory rate compared with normal subjects (p less than 0.01). Relative hyperventilation in patients with CHF started at the beginning of exercise and was observed both below and above the ventilatory threshold, which suggests that the excess ventilation was not directly related to earlier than normal metabolic acidosis. Thus abnormal ventilatory mechanisms contribute to exercise intolerance in CHF, and excess ventilation is associated with both a higher physiologic dead space and an abnormal breathing pattern. The high dead space is most likely due to ventilation-perfusion mismatching in the lungs, which is related to poor cardiac output, and the abnormal breathing pattern appears to be an effort to reduce the elevated work of breathing that is caused by high pulmonary pressures and poor lung compliance.

Neonatal Bilirubin Production Estimated from “End-Tidal” Carbon Monoxide Concentration

The relationship between the pulmonary excretion rate of carbon monoxide (VECO) and the concentration of CO, in a sample of breath, drawn through a nasopharyngeal catheter at end-expiration, was assessed in 25 studies of nine preterm and 14 term infants. The VECO and this approximate end-tidal sample of CO (ETCO) correlated significantly over a wide range of CO elimination rates: VECO = 10.45 ETCO + 2.25 (n = 25, r = 0.95). The ETCO correctly predicted elevations in VECO > 2 SD of the mean VECO for normal infants (13.9 ± 3.5 μl/kg/h), with 90% sensitivity and 73% specificity (p < 0.01). Three subjects with Rh isoimmune hemolytic disease were easily identified by the ETCO as well as the VECO. The ETco is a simple, noninvasive measurement for rapidly identifying infants with significant hemolytic disease.

Severe metabolic acidosis after acute naproxen sodium ingestion

Naproxen, a nonsteroidal anti-inflammatory drug (NSAID), is a propionic acid derivative that possesses analgesic and antipyretic properties through inhibition of prostaglandin synthesis. The propionic acids have been considered the least toxic of the NSAIDs, and one, ibuprofen, is currently available as an over-the-counter medication. Though acidosis has been reported with ibuprofen, no such occurrence has been reported for naproxen sodium. We report the case of a 15-year-old girl who presented with severe metabolic acidosis and seizures that rapidly followed naproxen sodium ingestion. Serum bicarbonate levels returned to normal 12 hours after admission and correlated with the known pharmacokinetics of naproxen. The pharmacokinetics of naproxen and treatment of its overdose, and possible mechanisms of metabolic acidosis are reviewed.