Cerebral oxygenation during exercise in patients with terminal lung disease

STUDY OBJECTIVES: In patients with terminal lung disease who were exercising, we assessed whether improved arterial O2 saturation with an increased fraction of inspired oxygen (FIO2) affects cerebral oxygenation. DESIGN: Randomized, crossover. PATIENTS AND METHODS: The cerebral changes in oxyhemoglobin (DeltaHbO2) and changes in deoxyhemoglobin (DeltaHb) levels were evaluated using near-infrared spectrophotometry and the middle cerebral artery (MCA) mean velocity (V(mean)) was determined by transcranial Doppler ultrasonography in 13 patients with terminal lung disease (New York Heart Association class III-IV). Patients were allocated to an FIO2 of either 0.21 or 0.35 during incremental exercise with 15 min between trials. RESULTS: Peak exercise intensity (mean [+/- SE], 26 +/- 4 W) reduced the arterial O2 pressure (at rest, 64 +/- 3 mm Hg; during exercise, 56 +/- 3 mm Hg) and the arterial oxygen saturation (SaO2) [at rest, 92 +/- 2%; 87 +/- 2%; p < 0.05], while the arterial CO2 pressure was not significantly affected. The MCA V(mean) increased from 49 +/- 5 to 63 +/- 7 cm/s (p < 0.05) as did the DeltaHb, while the DeltaHbO2 remained unaffected by exercise. With an elevated FIO2, the SaO2 level (at rest, 95.8 +/- 0.7%; during exercise, 96.0 +/- 1.0%) and arterial O2 pressure (at rest, 102 +/- 11 mm Hg; during exercise, 100 +/- 8 mm Hg) were not significantly affected by exercise, and the levels of blood oxygenation remained higher than the values established at normoxia (p < 0.05). The MCA V(mean) increased to a level similar to that achieved during control exercise (ie, to 70 +/- 11 cm/s). In contrast to control exercise, DeltaHb decreased while DeltaHbO2 increased during exercise with 35% O2 (p < 0.05). CONCLUSION: An O2-enriched atmosphere enabled patients with terminal lung disease to maintain arterial O2 saturation during exercise. An exercise-induced increase in cerebral perfusion was not affected by hyperoxia, whereby the enhanced availability of oxygenated hemoglobin increases cerebral oxygenation. The clinical implication of the study is that during physical activity patients with terminal lung disease are recommended to use an elevated FIO2 to protect cerebral oxygenation.     

Influence of hypercapnia and/or hypoxemia and metabolic acidosis on theophylline kinetics in the conscious rabbit

This study investigated the effect of acute changes in blood gases and pH on theophylline kinetics. Groups of 6 conscious rabbits were exposed to air (control) or to a high CO2 and/or low O2 atmosphere for 570 minutes, or received 47 ml/kg of 0.3N HCl by gavage. Once blood gases or pH were stabilized, they received 2.5 mg/kg theophylline intravenously. Urine, blood samples, and cerebrospinal fluid were collected. Metabolic acidosis did not modify theophylline kinetics. Theophylline serum concentrations increased with hypercapnia (p less than 0.05), hypoxemia (p less than 0.01), and hypercapnia combined with hypoxemia (p less than 0.001), compared with those in control animals. These increases were related to a decrease in theophylline nonrenal clearance (Clnr). Thus, Clnr decreased from 1.52 +/- 0.05 ml/min/kg in control animals to 1.13 +/- 0.13 in hypercapnia (p less than 0.01), 1.09 +/- 0.09 in hypoxemia (p less than 0.001), and 1.02 +/- 0.02 in hypoxemia combined with hypercapnia (p less than 0.001). Theophylline protein binding was not affected by any of the experimental conditions. The ratio of central nervous system to serum theophylline concentration was increased by 16% (p less than 0.05) with hypercapnia combined with hypoxemia. It was concluded that both hypercapnia and/or hypoxemia decreased theophylline biotransformation. Such a decrease may be the cause of toxicity.     

A comparative study of the effects of almitrine bismesylate and lateral position during unilateral bacterial pneumonia with severe hypoxemia.

The management of patients with unilateral pneumonia and severe hypoxemia often represents a therapeutic challenge. Mechanical ventilation with the diseased lung uppermost may improve gas exchange, but it is not devoid of adverse effects. No hemodynamic measurements have been reported in patients ventilated in this manner; therefore, whether or not the improvement in PaO2 is counterbalanced by hemodynamic deterioration remains unknown. Almitrine bismesylate is a drug that seems able to improve gas exchange in patients with chronic obstructive pulmonary disease or the adult respiratory distress syndrome. The increase in PaO2 after its administration has been attributed to an improvement in ventilation-perfusion relationships. Its use has never been reported during unilateral pneumonia with severe hypoxemia. We therefore compared its effects with those of lateral position in eight consecutive mechanically ventilated patients with unilateral pneumonia. Blood gas and hemodynamic measurements were performed both at maintenance FIO2 and at an FIO2 of 1.0. Almitrine (1 mg/kg over 1 h) had no effect on PaO2 under either FIO2 condition. Cardiac output remained unchanged, but mean pulmonary artery pressure increased from 22.5 +/- 1.2 to 26.5 +/- 1.3 mm Hg (p < 0.02). By contrast, lateral position had striking effects on PaO2, which increased from 100 +/- 14 mm Hg in supine position to 156 +/- 23 mm Hg (p < 0.01) when the abnormal lung was placed uppermost at maintenance FIO2 and from 207 +/- 21 (supine) to 300 +/- 28 mm Hg (lateral) (p < 0.01) at FIO2 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of propranolol on arterial oxygenation and oxygen transport to tissues in patients with cirrhosis

Patients with cirrhosis may show ventilation-perfusion (VA/Q) inequality in the absence of any intrinsic heart or lung disease. However, the high cardiac output of cirrhosis generally prevents or minimizes the appearance of a severe degree of arterial hypoxemia. Propranolol has been used to reduce cardiac output and portal pressure in these patients. We wondered whether it might alter arterial oxygenation and reduce O2 transport to tissues. We studied eight patients (three women) 54 +/- 3 (SEM) yr of age before and after intravenous propranolol (0.1 mg/kg followed by 2 mg/h). Cardiac output (QT) fell from 7.8 +/- 0.7 to 6.0 +/- 0.7 L/min (p less than 0.05), and portal pressure was reduced (22 +/- 2 to 19 +/- 2 mm Hg, p less than 0.01). Arterial PO2 did not change (88 +/- 4 to 89 +/- 5 mm Hg) because the fall in mixed venous PO2 (43 +/- 1 to 40 +/- 1 mm Hg, p less than 0.01) that followed the lower QT was counterbalanced by a lower intrapulmonary shunt (multiple inert gas technique) (4 +/- 2 to 2 +/- 1%, p less than 0.05) and a shift of the VA/Q distributions toward a higher VA/Q ratio. Paralleling the fall in QT, oxygen transport to tissues (QO2) was reduced (19 +/- 2 to 14 +/- 1 ml/min/kg, p less than 0.01). However, O2 uptake (VO2) remained constant (3.4 +/- 0.2 to 3.6 +/- 0.2 ml/min/kg) because O2 extraction by the tissues increased appropriately (22 +/- 2 to 28 +/- 1%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of almitrine bismesylate on hypoxemia in chronic obstructive pulmonary disease

Almitrine bismesylate was studied for its effects on hypoxemia in 67 patients with chronic obstructive lung disease in a placebo-controlled, double-blind study. Arterial Po2 rose by 11.2 mm Hg (p less than 0.05) in 21 patients receiving 100 mg twice daily and by 6.0 mm Hg (p less than 0.05) in 22 patients receiving 50 mg twice daily. Arterial Pco2 decreased by 3.8 mm Hg (p less than 0.05) in the group receiving 100 mg twice daily but was unchanged in patients receiving 50 mg twice daily. Lung function was unaltered except for a slight increase in forced mid-expiratory flow in both dosage groups (p less than 0.05). The major side effect was the unexplained worsening of dyspnea, which occurred in 4 patients (19%) receiving 100 mg twice daily, 2 (9%) receiving 50 mg twice daily group, and 1 (4%) receiving placebo. Almitrine bismesylate improves arterial blood gas values in patients with chronic obstructive lung disease, apparently by reducing intrapulmonary ventilation-perfusion mismatching, and appears to be useful in the long-term management of these patients.     

Noninvasive positive-pressure ventilation vs. conventional oxygen supplementation in hypoxemic patients undergoing diagnostic bronchoscopy

OBJECTIVE: We have reported previously on the use of noninvasive positive-pressure ventilation (NPPV) to assist spontaneous breathing in high-risk hypoxemic patients (i.e., PaO(2)/fraction of inspired oxygen [FIO(2)] ratio, < or = 100) who are undergoing diagnostic fiberoptic bronchoscopy (FOB). The efficacy of this intervention in patients with less severe forms of hypoxemia (i.e., PaO(2)/FIO(2) ratio, < 200) is unknown. PATIENTS AND METHODS: Twenty-six patients with PaO(2)/FIO(2) ratios < or = 200 who required bronchoscopic BAL for suspected nosocomial pneumonia were entered into the study. Thirteen patients were randomized during FOB to receive NPPV, and 13 patients were randomized to receive conventional oxygen supplementation by Venturi mask. The primary end points were changes in the PaO(2)/FIO(2) ratio during FOB and within 60 min of terminating the procedure. RESULTS AND OUTCOME: At study entry, the two groups were similar in terms of age, simplified acute physiologic score II values, and cardiorespiratory parameters. During FOB, the mean (+/- SD) PaO(2)/FIO(2) ratio increased by 82% in the NPPV group (261 +/- 100 vs 139 +/- 38; p < 0.001) and decreased by 10% in the conventional oxygen supplementation group (155 +/- 24 to 139 +/- 38; p = 0.23). Sixty minutes after undergoing FOB, the NPPV group had a higher mean PaO(2)/FIO(2) ratio (176 +/- 62 vs 140 +/- 38; p = 0.09), a lower mean heart rate (91 +/- 18 vs. 108 +/- 15 beats/min; p = 0.02), and no reduction in mean arterial pressure in comparison to a 15% decrease from the baseline in the control group. One patient in the NPPV group and two patients in the control group required nonemergent intubation. Major bacterial isolates included Staphylococcus aureus (7 of 30 isolates; 23%) and Pseudomonas aeruginosa (12 of 30 isolates; 40%). CONCLUSION: In patients with severe hypoxemia, NPPV is superior to conventional oxygen supplementation in preventing gas-exchange deterioration during FOB with better hemodynamic tolerance.     

Effect of naloxone on the pulmonary vascular responses to graded levels of intracranial hypertension in anesthetized sheep

We increased intracranial pressure (ICP) in anesthetized sheep for 3 h by connecting the cisterna magna to an elevated reservoir of buffered saline. We monitored systemic and pulmonary vascular pressures, pulmonary blood flow, and the flow of lymph from the lungs. The volume and protein concentration of the lymph were used to assess changes in lung vascular permeability-surface area. Extravascular lung water was measured postmortem, and in vivo indicator dilution studies were used to measure permeability-surface area product (PS urea) of the lung circulation for a small hydrophillic molecule (14C-urea) and extravascular water volume (VH2O). These studies were done in 16 sheep with ICP raised to 0, 60, or 100 mmHg. Thirteen other sheep received naloxone before and during elevation of ICP to 0, 60, or 100 mmHg. Elevation of ICP increased pulmonary artery pressure (Control: 16 +/- 3 cmH2O; ICP: 60 mmHg = 16 +/- 2 cmH2O; ICP: 100 mmHg = 23 +/- 2 cmH2O), cardiac output (Control: 2.7 +/- 0.1 L/min; ICP: 60 mmHg = 3.3 +/- 0.05, p less than 0.05; ICP: 100 mmHg = 5.3 +/- 1.0, p less than 0.05), lung lymph flow (Control: 94 +/- 8% baseline; ICP: 60 mmHg = 193 +/- 25% baseline, p less than 0.05; ICP: 100 mmHg = 285 +/- 38% baseline, p less than 0.05), PS urea (Control: 7.0 +/- 0.5 ml/s; ICP: 60 mmHg = 11.0 +/- 3.7 ml/s; ICP: 100 mmHg = 12.4 +/- 1.3 ml/s, p less than 0.05), and VH2O (Control: 93 +/- 8% baseline; ICP: 60 mmHg = 112 +/- 6% of baseline; ICP: 100 mmHg = 129 +/- 13% of baseline, p less than 0.05) proportional to the level of ICP. Sheep with ICP raised to 100 mmHg had modestly increased lung water (pulmonary edema).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary gas exchange response to oxygen breathing in acute lung injury

The mechanisms and time course of the pulmonary gas exchange response to 100% O(2) breathing in acute respiratory failure needing mechanical ventilation were studied in eight patients with acute lung injury (ALI) (48 +/- 18 yr [mean +/- SD]) and in four patients (66 +/- 2 yr) with chronic obstructive pulmonary disease (COPD). We postulated that, in patients with ALI while breathing 100% O(2), the primary mechanism of hypoxemia, i.e., increased intrapulmonary shunt, would further worsen (increase) as a result of reabsorption atelectasis. Respiratory and inert gases, and systemic and pulmonary hemodynamics were measured at maintenance fraction of inspired oxygen (FI(O(2))-m), at 30 and 60 min while breathing 100% O(2), and then at 30 min of resuming FI(O(2))-m. During 100% O(2) breathing, in patients with ALI, Pa(O(2)) (by 207 and 204 mm Hg; p < 0.01 each), Pa(CO(2)) (by 4 mm Hg each) (p < 0.05 each), and intrapulmonary shunt (from 16 +/- 10% to 22 +/- 11% and 23 +/- 11%) (p < 0.05 each) increased respectively. By contrast, in patients with COPD, Pa(O(2)) (by 387 and 393 mm Hg; p < 0.001 each), Pa(CO(2)) (by 4 and 5 mm Hg) and the dispersion of pulmonary blood flow (log SDQ) (from 1.33 +/- 0.10 to 1.60 +/- 0.20 and 1.80 +/- 0.30 [p < 0.05]) increased, respectively. In patients with ALI, the breathing of 100% O(2) deteriorates intrapulmonary shunt owing to collapse of unstable alveolar units with very low ventilation-perfusion (V A/Q) ratios, as opposed to patients with COPD, in whom only the dispersion of the blood flow distribution is disturbed, suggesting release of hypoxic pulmonary vasoconstriction.     

Mild isocapnic hypoxia enhances the bronchial response to methacholine in asthmatic subjects

We studied the effect of mild isocapnic hypoxia (FIO2 = 15.5%) on lung mechanics, heart rate, circulating plasma catecholamines, and bronchial responsiveness to methacholine in ten asthmatic adults. Hypoxia did not alter lung mechanics (i.e., dynamic pulmonary compliance [CLdyn], pulmonary resistance [RL]) nor did it increase plasma catecholamines, but it significantly increased bronchial responsiveness to aerosolized methacholine, as assessed by the fall in forced expiratory volume in one second (FEV1: 1.2 +/- 0.18 versus 0.9 +/- 0.14 L/s, p less than 0.05), the rise in RL (RL: 19.1 +/- 1.4 versus 8.4 +/- 1 cm H2O/L/s, p less than 0.05), and the steeper slope of the dose-response curve to methacholine. We concluded that the hypoxic characteristic of asthmatic attacks may aggravate airflow obstruction.     

Total respiratory system compliance in asymptomatic infants with cystic fibrosis

Total respiratory system compliance (Crs) was assessed by the weighted spirometer method in 11 asymptomatic infants (mean age, 11.1 months) with cystic fibrosis (CF) who had normal chest radiographs. In addition to Crs, functional residual capacity (FRC), respiratory rate (RR), and mixing index (MI) were measured. There was no significant difference in FRC between normal controls (n = 36) and CF infants (190 +/- 69 versus 186 +/- 63 ml; p less than 0.8), although the CF group had a higher RR (32 +/- 7 versus 37 +/- 7 BPM; p less than 0.05) and a lower MI (45 +/- 7 versus 40 +/- 8%; p less than 0.05), reflecting an abnormal distribution of ventilation. The lower Crs (9.0 +/- 3.4 versus 5.7 +/- 2.8 ml/cm H2O; p less than 0.01) and the lower specific compliance, Crs/FRC (0.049 +/- 0.013 versus 0.029 +/- 0.007 1/cm H2O; p less than 0.0001), in the CF group were the parameters that best distinguished the normal control and CF infants. We conclude that the measurement of Crs represents a noninvasive method for detecting early pulmonary function abnormalities in CF infants.     

Altered urinary excretion of elastin cross-links in premature infants who develop bronchopulmonary dysplasia

In order to determine whether elastin degradation is increased in infants whose respiratory insufficiency requires ventilation with high concentrations of O2, we quantitated, by amino acid analysis, the elastin degradation products (desmosines) excreted in the urine of 14 premature male infants during the first 3 wk of life. Eight of these infants, the "low-O2" infants, did not have severe lung disease and did not require more than 40% O2 beyond the first 8 h of life. The other 6 infants, selected retrospectively because they developed bronchopulmonary dysplasia (BPD), were ventilated with more than 60% O2 for at least the first 72 h of life. The pattern of desmosine excretion observed in infants who developed BPD differed significantly (p less than 0.05) from the excretion pattern seen in "low-O2" infants during the first 3 wk of life. At the end of the first week of life, desmosine excretion was significantly greater (p less than 0.05) in the infants who later developed BPD than in the "low-O2" infants without severe lung disease. From Days 7-9 to 20-22, desmosine excretion increased in the "low-O2" infants from 6.9 +/- 1.7 micrograms/kg to 9.0 +/- 3.5 micrograms/kg. In contrast, desmosine excretion did not remain elevated in the BPD infants, decreasing from 10.6 +/- 2.2 micrograms/kg to 6.1 +/- 2.9 micrograms/kg during the same period. In the BPD infants, elevated desmosine excretion through Day 9 is likely to reflect lung injury, whereas decreased desmosine excretion beyond Day 9 suggests that elastin synthesis and turnover is impaired, possibly as a result of nutritional deficiencies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lung mechanics and oxygen consumption during spontaneous ventilation and severe heart failure.

The effects of acute heart failure on lung mechanics and oxygen consumption (VO2) during normocarbic spontaneous ventilation were studied in 21 anesthetized pigs. Heart failure severe enough to double oxygen extraction (O2ex) was induced with intravenous esmolol boluses and infusion. Compared to normal, the inspiratory elastic work of breathing (Wel) increased from 335 +/- 371 (mean +/- SD) to 559 +/- 48 mm Hg.ml (p less than 0.003) during heart failure, lung compliance (CL) fell from 121 +/- 144 to 22 +/- 15 ml/mm Hg (p less than 0.05), and respiratory power climbed from 140 +/- 200 to 245 +/- 214 mm Hg.ml.min-1 (p less than 0.002). These mechanical changes were accompanied by a decrease in both VO2 (221 +/- 61 to 191 +/- 50 mlO2/min, p less than 0.05) and oxygen delivery (DO2) (680 +/- 240 to 260 +/- 90 mlO2/min, p less than 0.004). The VO2/DO2 ratio doubled (p less than 0.0002), confirming increased O2ex. In conclusion, severe acute heart failure decreased CL, and increased Wel and respiratory power significantly. The depressed cardiac output limits both DO2, and to some extent, VO2. However, a greater proportion of the delivered O2 is consumed, supplying indirect evidence which suggests that the respiratory muscles' VO2 increases as a consequence of increased power expenditure.     

Oxygen consumption during spontaneous ventilation with acute lung injury in anesthetized pigs

Acute lung injury causes a restrictive pulmonary defect, decreases lung compliance, and increases the work of breathing. We wished to determine the oxygen cost of the increased elastic work of breathing associated with acute lung injury. Extracorporeal venous circulation with a membrane lung was used to extract CO2 and to induce apnea in 14 anesthetized pigs. Data were collected during 4 experimental states: during spontaneous ventilation and apnea when the animals' lungs were normal, and after acute lung injury developed because of oleic acid administration. Acute lung injury decreased lung compliance from 101 +/- 79 (mean +/- SD) to 52 +/- 25 ml/cm H2O (p less than 0.04), and increased the elastic work of breathing from 700 +/- 590 to 1,060 +/- 630 ml.cm H2O (p = 0.01). During spontaneous ventilation, the increases in total O2 consumption and the O2 cost of breathing caused by acute lung injury were sufficiently small as to be undetectable, and, therefore, less than 3 to 4% of basal O2 consumption despite markedly increased elastic work and ventilatory power requirements. The increase in O2 consumption imposed by acute lung injury was small enough (less than 3 to 4% of total O2 consumption) that it appears to be clinically insignificant.     

Mechanical properties of the rabbit upper airway during hypoxia and hypercapnia

It has been suggested that the response of upper airway muscles to hypoxia may be different from the response of these muscles to hypercapnia. We therefore measured pulmonary ventilation and the mechanical properties of the isolated upper airway in 9 anesthetised rabbits during respiration of hypoxic and hypercapnic gas mixtures. Each animal was exposed to several levels of elevated inspiratory CO2 fraction, FICO2 (0.03 to 0.17) and depressed inspiratory O2 fraction, FIO2 (0.19 to 0.09). The steady-state ventilatory response, the tidal pressure in the upper airway (PTUA) and the upper airway elastance were measured under each condition. Straight lines were calculated by least squares regression relating pulmonary VT to FICO2 and FIO2 and PTUA to FICO2 and FIO2. The PTUA was estimated graphically at two levels of hypoxia and hypercapnia producing equal augmentation of VT. The ratio of PTUA during hypoxia to PTUA during hypercapnia was 1.06 +/- 0.21 (mean +/- 95% C.I.) at low VT and 1.15 +/- 0.25 at high VT. Elastance of the upper airway rose from 6.25 +/- 1.13 cmH2O/ml under control conditions to a maximum of 7.95 +/- 1.24 cmH2O/ml (P less than 0.05) during hypercapnia and to a maximum of 8.02 +/- 1.17 cmH2O/ml (P less than 0.05) during hypoxia. There was no difference between the mean (+/- 95% C.I.) change associated with hypercapnia (1.64 +/- 1.08 cmH2O/ml) and the mean change associated with hypoxia (1.77 +/- 1.26 cmH2O/ml). We concluded that hypoxia did not result in a greater change in upper airway mechanical properties than hypercapnia.     

Effects of indomethacin on pulmonary hemodynamics and gas exchange in patients with pulmonary artery hypertension, interference with hydralazine

To assess the ability of indomethacin (Indo) to influence pulmonary vascular tone in patients with chronic lung disease, we studied the hemodynamic and gas exchange alterations induced by a 50-mg indomethacin infusion in 10 patients suffering from varying degrees of pulmonary artery hypertension and hypoxemia. The most pronounced effects were observed 3 h after Indo administration. Mean systemic arterial pressure (Psa) increased from 76 +/- 4 to 86 +/- 4 mm Hg (p less than 0.01), whereas mean pulmonary arterial pressure (Ppa) was unchanged. The cardiac index (CI) decreased from 3.1 +/- 0.2 to 2.8 +/- 0.2 L/min/m2 (p less than 0.02) because of the reduced heart rate, which decreased from 86 +/- 5 to 80 +/- 4 beats/min (p less than 0.05). Systemic and pulmonary vascular resistance indexes increased, respectively, from 22 +/- 2 to 27.5 +/- 2 U/m2 (p less than 0.001) and from 11.9 +/- 2 to 13.4 +/- 2 U/m2 (p less than 0.05). We measured an increase in PaO2, from 49.5 +/- 4 to 57.5 +/- 4 mm Hg (p less than 0.001) simultaneously with a reduced venous admixture, from 39.5 +/- 4 to 30.5 +/- 3% (p less than 0.001). The calculated PO2 uptake was unchanged, but mixed venous O2 tension increased from 30.5 to 33.5 mm Hg (p less than 0.01). Because Indo may interfere with the hypotensive effect of hydralazine and because hydralazine has been proposed in the treatment of patients with pulmonary hypertension, 7 of these patients also received 0.35 mg/kg hydralazine and Indo plus hydralazine (Indo + H) injected simultaneously.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spontaneous desaturations in intubated very low birth weight infants with acute and chronic lung disease.

Patients with chronic lung disease (CLD) have frequent episodes of spontaneous desaturations. Utilizing computerized pulse oximetry (CPO) we quantified the frequency and severity of spontaneous desaturations in very low birth weight (VLBW) infants with CLD. Thirty-four studies by CPO were performed in intubated infants for 4 hours; 17 patients (birth weight, 550-980 g; postnatal age 28-85 days) had CLD, and 17 (birth weight, 520-980 g; postnatal age, 1-7 days) had acute lung disease. Oxygen saturation (SaO2) was measured with the Nellcor N-200 oximeter, its serial output (updated once a second) captured by a computer. Pulse rate, pulse amplitude, and heart rate were also monitored continuously. We measured respiratory system mechanics in 23 patients. Tidal volume (VT), respiratory system compliance (Crs), and resistance (Rrs) were obtained by the PeDS system. Spontaneous desaturation to SaO2 less than 90% occurred for 4.5% of the time in acute patients vs. 27.1% of the time in chronic patients (P less than 0.0001); to SaO2 less than 85%, 0.7% vs. 7.6% of the time in acute vs. chronic patients (P less than 0.002); and to SaO2 less than 80%, 0.4% vs. 2.6% of the time in acute vs. CLD patients (P less than 0.05). Rrs was significantly higher in the ventilated patients with CLD (174 cmH2O/L/s) than in the ventilated patients with acute lung disease (94 cmH2O/L/s, P less than 0.0001). The mean Crs values of the two groups were comparable. Our preliminary data indicate that VLBW infants with CLD receiving assisted ventilation have a greater number of spontaneous desaturation episodes, as compared to patients with acute lung disease.     

Compliance measurement in respiratory distress syndrome: the prediction of outcome

Dynamic compliance (Cdyn) measurements within the first three days of life predicted survival in 60 preterm infants suffering from respiratory distress syndrome. Cdyn was measured in 47 survivors at 2.3 +/- 1.4 days of life and in 13 nonsurvivors on 2.7 +/- 1.7 days. All nonsurvivors died from respiratory failure within the first two weeks of life. Mean Cdyn of the survivors was 0.83 +/- 0.33 ml/cm H2O and of the nonsurvivors 0.35 +/- 0.19 ml/cm H2O (p less than 0.001). Cdyn values below 0.45 ml/cm H2O predicted 11 of 13 deaths in infants, and Cdyn measurements above this value predicted 45 of 47 survivals, with a specificity of 81% and a sensitivity of 89%. Eleven of the survivors, who subsequently developed bronchopulmonary dysplasia (BPD), had a mean Cdyn of 0.56 +/- 0.23 ml/cm H2O. When these infants were matched with infants of comparable weight without evidence of BPD, the BPD group had a significantly lower Cdyn (p less than 0.05). Cdyn measurements during the first three days of life are useful in predicting outcome of respiratory failure secondary to respiratory distress syndrome.     

Hypoxia and hypercarbia increase bronchial blood flow through bronchopulmonary anastomoses in anesthetized dogs

We studied the effect of systemic hypoxemia and hypercarbia on the bronchial blood flow in open-chested, anesthetized dogs. The pulmonary artery and vein of the left lower lobe (LLL) were isolated with cannulas and connected to reservoirs set at atmospheric pressure relative to the base of the LLL. That fraction of the bronchial arterial flow (Qbr) to the LLL, which flowed through the bronchopulmonary anastomoses into these reservoirs, was continuously measured. The LLL was inflated continuously with 6% CO2 and air at a constant alveolar pressure of 10 cm H2O. Systemic arterial O2 tension (PaO2) and arterial CO2 tension (PaCO2) were varied by separately ventilating the right lung through a bifurcated endotracheal tube. A 10-min period was allowed for stabilization after each change in experimental condition. Anastomotic Qbr was measured for 5 min during each experiment. In separate animals, similar studies were performed before and 30 min after intravenously administered indomethacin (6 mg/kg body weight). During normoxic conditions when PaO2 was 79 +/- 8 torr (mean +/- SEM), the mean anastomotic Qbr was 5.7 +/- 2.0 ml/min (n = 9). This flow increased to 8.3 +/- 2.5 ml/min (p less than 0.05) during hypoxemic conditions (PaO2, 38 +/- 3). The anastomotic Qbr increased from 5.8 +/- 1 to 9.0 +/- 2 ml/min (p less than 0.005) when PaCO2 was increased from 23 +/- 1 to 47 +/- 2 torr (n = 11). Pretreatment with intravenously administered indomethacin blocked both the hypoxemia-induced (n = 4) and hypercarbia-induced (n = 4) increases in anastomotic Qbr. We conclude that both hypoxemia and hypercarbia increased the anastomotic Qbr through a mechanism involving cyclooxygenase products of arachidonic acid.     

Serial measurement of pulmonary mechanics assists in weaning from extracorporeal membrane oxygenation in neonates with respiratory failure

Extracorporeal membrane oxygenation (ECMO) is a highly invasive therapy for intractable neonatal respiratory failure, and serious complications may occur with increasing duration of bypass. Weaning from bypass is empirical at present. Thus, there is a need to accurately predict when infants can be successfully decannulated. We hypothesized that pulmonary mechanics would reflect lung recovery and, therefore, predict successful weaning from ECMO. We measured pulmonary mechanics daily in 22 neonates, at gestational age of 37.8 +/- 0.6 weeks (SE) requiring ECMO for severe respiratory failure (oxygen index 66 +/- 6). Pulmonary resistance (Rpul), dynamic compliance (Cdyn), and tidal volume (VT) were measured. Rpul did not predict lung recovery. Cdyn within 24 hours of starting ECMO was 0.3 +/- 0.04 ml/cm H2O. Cdyn within 24 hours of weaning from ECMO was 1.2 +/- 0.09 ml/cm H2O (p less than 0.001). All 22 infants had Cdyn greater than 0.6 ml/cm H2O at the time of decannulation, but four infants (20 percent) with Cdyn less than 0.6 ml/cm H2O could not be weaned from ECMO within 20 hours (p less than 0.01). Thus, a minimum Cdyn of 0.6 ml/cm H2O is associated with successful weaning from ECMO. Cdyn of 0.8 ml/cm H2O provided better overall discrimination between those who could be successfully weaned from ECMO. We conclude that serial measurement of dynamic pulmonary compliance predicts successful weaning from ECMO.     

Cardiopulmonary effects of enprofylline. A xanthine with weak adenosine receptor antagonism in patients with severe chronic lung disease

The acute cardiovascular effects of a new xanthine, enprofylline, were studied in patients with chronic lung disease. The studies were done during cardiac catheterization (n = 12) and by radionuclide ventriculography (n = 6). Enprofylline was given intravenously, 2 mg/kg, and measurements were done after ten and 30 min. Enprofylline reduced the mean pulmonary artery pressure from 30 +/- 10 to 26 +/- 7 mm Hg (p less than 0.05) and the mean systemic arterial pressure from 92 +/- 17 to 83 +/- 15 mm Hg (p less than 0.01), increased the heart rate from 89 +/- 15 to 100 +/- 18 beats/min (p less than 0.01) and reduced the stroke volume from 55 +/- 12 to 48 +/- 12 ml (p less than 0.05) after 30 min. Radionuclide ventriculography revealed unchanged ejection fraction of left and right ventricles after enprofylline. None of the patients experienced serious side effects of the drug. Thus, enprofylline induced modest acute cardiovascular effects with a chronotropic response together with a small vasodilation in pulmonary and systemic circulation.