Comparison of four demand oxygen delivery systems at rest and during exercise for chronic obstructive pulmonary disease.

OBJECTIVES: The aim of this study was to assess the performance of four demand oxygen delivery systems (DODS) in improving oxygenation and effort tolerance, at rest and during exercise, in chronic obstructive pulmonary disease (COPD) patients. MATERIALS AND METHODS: Thirteen COPD patients were prospectively included. Four DODS (Oxiclip, Versatile, Venture and Impulse) were compared with continuous-flow oxygen (CFO). Nine of these patients performed 6-min walking tests on room air and on 3 l/min oxygen by DODS and CFO; Oxygen saturation, walking distance and the Borg dyspnea score were recorded. RESULTS: With all four DODS devices arterial oxygenation was improved with lower oxygen flow rates than with CFO. Oxygen economy was best with Impulse, but at a cost of less satisfactory oxygenation. Exercise desaturation was similar with CFO, Oxiclip, Venture, and Impulse but significantly higher with Versatile (P < 0.05). Borg dyspnea scores were similar with CFO, Oxiclip, Venture, and Versatile but worse with Impulse (P < 0.05). There was no significant difference in walking distances. CONCLUSIONS: All four DODS improved oxygen saturation and saved oxygen. However, performance was better with the two devices (Oxiclip and Venture) that deliver a bolus of oxygen at inspiration onset.

Use of glass capillaries avoids the time changes in high blood PO(2) observed with plastic syringes.

STUDY OBJECTIVES: In adults, arterial blood samples are usually drawn using plastic syringes. In contrast to glass syringes, plastic syringes let oxygen diffuse through their wall. This results in PO(2) changes during storage, especially when PO(2) is high. An alternative to glass syringes is the Microsampler (Roche Diagnostics; Schaffhausen, Switzerland), a commercially available device consisting of a heparinized glass capillary fitted with a 26-gauge needle and used to collect arterial blood in the same way as a plastic syringe fitted with a needle. DESIGN: We evaluated the performance of the Roche Microsampler for storing arterial blood in view of PO(2) measurement, comparatively with glass and plastic syringes. Five approximate initial PO(2) levels (650, 400, 200, 130, and 80 mm Hg) and two storage temperatures (ambient temperature and 4 degrees C) were studied. SETTINGS: Bench study. RESULTS: Plastic syringes allowed reliable measurement of PO(2) values when initial PO(2) was too low to ensure complete hemoglobin oxygen saturation, but were associated with time-dependent underestimation of PO(2) at higher initial PO(2) values. No such underestimation occurred with the Roche Microsampler stored at 4 degrees C for up to 1 h for all PO(2) levels studied. CONCLUSION: The Roche Microsamplers appeared to be reliable devices in preventing oxygen diffusion.

Optimal handling of blood samples for routine measurement of lactate and pyruvate.

Blood lactate and pyruvate are of critical importance for the diagnosis of mitochondrial diseases. To determine guidelines for adequate blood pyruvate and lactate determinations, intraindividual studies were carried out on 10 subjects, and the influences of venostasis, delay before deproteinization, and pH in the pyruvate assay were analyzed. Delays of 1 hour or more before deproteinization of samples induced major elevations of lactate-pyruvate ratios. The lactate-pyruvate ratio correlated positively with pH in the pyruvate assay, and inadequate pH appeared as a largely underestimated cause of misleading results, while venostasis was a minor source of errors.

Measurement of gastric intramucosal pH in patients with cirrhosis and portal hypertensive gastropathy.

OBJECTIVES: Patients with cirrhosis often have gastric mucosal lesions associated with portal hypertension. Microvascular changes due to portal hypertension may cause mucosal ischaemia. The decrease in intramucosal pH is used as an index of this condition. In this study we compared the gastric intramucosal pH in patients with cirrhosis and portal hypertension and in control group. METHODS: Estimates of pH were calculated using the Henderson-Hasselbalch equation, assuming that measured concentrations of CO2 in the gastric lumen (pCO2) and of HCO3- in arterial blood represented intramucosal CO2 and intramucosal HCO3- concentrations, respectively. Tonometer measurements of intragastric CO2, validated in vitro, were made in patients treated by famotidine (10 mg.h-1 continuous infusion) to suppress gastric acid secretion and minimize CO2 production from luminal gastric bicarbonate. Intramucosal pH was determined in 19 control patients (mean age: 50.2 years) and in 25 patients with cirrhosis and portal hypertensive gastropathy (mean age: 54.2 years). In the patients with cirrhosis the severity of mucosal and parietal abnormalities induced by portal hypertension were graded according to endoscopic score from 0 to 9 and endoscopic ultrasonography score from 0 to 3. RESULTS: The mean endoscopic and ultrasonographic scores were 5.0 and 1.8 respectively. The median gastric intramucosal pH of patients with cirrhosis (7.42; range: 7.36 to 7.53) was similar to that of the controls (7.42; range: 7.33-7.51). A positive correlation was found between intramucosal pH and severity of portal hypertensive gastropathy, in the antrum, but not in the fundus. CONCLUSION: These findings do not support the hypothesis that gastric mucosal lesions are the consequence of ischaemia in patients with cirrhosis.

Hemodynamic and gas exchange responses to infusion of acetylcholine and inhalation of nitric oxide in patients with chronic obstructive lung disease and pulmonary hypertension.

To investigate endothelium-dependent and endothelium-independent nitric oxide (NO) mediated pulmonary vasodilation in patients with chronic obstructive lung disease (COLD), we examined the responses to incremental infusion rates of acetylcholine (ACh) or inhaled NO on hemodynamic and gas exchange. In 13 patients, ACh (15 mg/min) decreased pulmonary artery pressure (Ppa) from 31 +/- 1 to 28 +/- 1 mm Hg (p < 0.01) and systemic arterial pressure while increasing cardiac index from 3.7 +/- 0.4 to 4.7 +/- 0.4 L/min/m2 (p < 0.01). Inhaling 40 parts per million (ppm) NO decreased Ppa from 32 +/- 1 to 26 +/- 1 mm Hg (p < 0.001) with no associated hemodynamic change. ACh reduced PaO2 from 57 +/- 3 to 48 +/- 2 mm Hg (p < 0.01) and increased venous admixture (QVA/QT) from 35 +/- 3 to 45 +/- 3% (p < 0.01). Inhaling 40 ppm NO increased PaO2 from 57 +/- 3 to 60 +/- 3 mm Hg (p < 0.01) and decreased QVA/QT from 36 +/- 3 to 32 +/- 3% (p < 0.01). Pulmonary vascular resistance changes were similar in response to 40 ppm NO or 15 mg/min ACh. In COLD patients, ACh produces both pulmonary and systemic vasodilation but impairs arterial oxygenation whereas inhaled NO induces selective pulmonary vasodilation while improving gas exchange. The resistance to ACh in some patients could be related to pulmonary endothelial dysfunction.

Mechanisms of impaired arterial oxygenation in patients with liver cirrhosis and severe respiratory insufficiency. Effects of indomethacin.

The mechanisms of impaired arterial oxygenation that occur in certain patients with chronic liver cirrhosis are still debated. In the present study, we investigated nine cirrhotic patients with severe respiratory disability (mean PaO2, 64 +/- 5 mm Hg), using the inert gas elimination technique to assess the distribution of ventilation-perfusion (VA/Q) ratios. We also determined shunt fraction during pure oxygen breathing, both in supine and sitting positions. To test the hypothesis that vasodilating prostaglandins could contribute to alter gas exchange in such patients with cirrhosis, we examined the hemodynamic and gasometric responses to indomethacin, 50 mg IV, in six of them. During baseline conditions, patients had high cardiac index (CI, 4.9 +/- 0.2 L/min/m2), and low pulmonary (PVR, 1.78 +/- 0.37 mm Hg/L/min/m2) or systemic (SVR, 17.7 +/- 1.15 mm Hg/L/min/m2) vascular resistances. Large intrapulmonary shunt fraction was documented in each patient with a mean value of 19.6 +/- 2.7 percent. Small perfusion in low VA/Q areas was associated with shunt in only three patients (2.5 to 5.3 percent of blood flow). Arterial PO2 was negatively related to shunt (p < 0.01) and to the dispersion of blood flow distribution (p < 0.02). There was no difference between measured and predicted PaO2. Shunt estimates from the inert gas and the 100 percent O2 breathing techniques were, respectively, 19.6 +/- 2.7 percent and 21.7 +/- 3.0 percent. During 100 percent oxygen breathing, changing from supine to sitting position decreased PaO2 from 401 +/- 50 to 333 +/- 64 mm Hg (p < 0.02), while O2 shunt remained unchanged, arteriovenous difference widened, and mixed venous PO2 decreased, from 61 +/- 3 to 47 +/- 4 mm Hg (p < 0.001). Indomethacin did not improve gas exchange or VA/Q distribution and did not affect systemic or pulmonary hemodynamics. The results show that in cirrhotic patients with severe respiratory disability, intrapulmonary shunting is the main determinant of impaired gas exchange, with no evidence of a defect in oxygen diffusion or an extrapulmonary shunt. Vasodilating prostaglandins do not appear to contribute to these alterations.

Effects of substance P and calcitonin gene-related peptide on the pulmonary circulation.

To assess the in vivo effects of the neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) on the pulmonary vascular bed, the hemodynamic responses to both CGRP and SP were examined in the in situ-perfused lung lobe of open-chest anesthetized pigs. Peptides were infused into the lobar artery under conditions of elevated pulmonary vascular tone by prostaglandin F2 alpha (PGF2 alpha, 20 micrograms/min). Pulmonary airway lobar dynamic compliance (Cdyn) and airway resistance (Re) were computed from simultaneously measured airway pressure and airflow entering the lobe through a Carlens endobronchial divider. PGF2 alpha infusion slightly reduced Cdyn (-20%) and increased Re (+11%) while lobar arterial pressure rose from 14 +/- 1 to 31 +/- 2 mmHg (n = 12). In these conditions, lobar artery infusion of SP (0.5-50 pmol/min) or CGRP (15-5,000 pmol/min) produced a dose-dependent decrease in the pressor response to PGF2 alpha, reaching -54 +/- 3 and -64 +/- 7%, respectively, without alterations in lung mechanics. On a molar basis, SP was more effective than CGRP; its vasodilatory effect was more rapid and of shorter duration. Higher CGRP infusion rates were not studied because of marked systemic hypotension. SP infused at 150, 500, and 1,000 pmol/min significantly reduced Cdyn by 12 +/- 2, 24 +/- 4, and 62 +/- 7%, respectively, but also induced a rise in lobar arterial pressure and a fall in systemic arterial pressure. The results show that both SP and CGRP are potent pulmonary vasodilators. In contrast to CGRP, which did not affect lung mechanics, high infusion rates of SP decreased Cdyn and increased Re.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of improvement in pulmonary gas exchange during growth in awake piglets.

Previous studies have shown a lower arterial PO2 (PaO2) in infants and young animals than in adults. To investigate the mechanism of this impairment of gas exchange we studied 13 piglets from 12 to 65 days of age. Two days after instrumentation we measured the distribution of ventilation-perfusion ratios (VA/Q) by use of the multiple inert gas technique on awake animals. We showed that PaO2 is lower in young animals, increasing from 72 +/- 11.5 Torr before 2 wk to 102 Torr at 2 mo. This hypoxemia is due to an enlarged alveolar-arterial O2 pressure difference that significantly decreases with age. This impairment in gas exchange is not due to shunting (0.6 +/- 1.3%). Mean dead space (36 +/- 11%) was not related to age. Mean modes of perfusion and ventilation did not differ significantly between age groups. However, the dispersion of perfusion as expressed by its logSD decreased significantly with age, whereas dispersion of ventilation remained constant. Furthermore, in the young animals only, a significant difference was evidenced between measured alveolar-arterial PO2 gradient and the value predicted by the inert gas model. We therefore conclude that the impairment of gas exchange in piglets is due to two mechanisms: VA/Q mismatch and diffusion limitation for O2.

Low VA/Q areas: arterial-alveolar N2 difference and multiple inert gas elimination technique.

In 16 critically ill patients the arterial-alveolar N2 difference and data from the multiple inert gas elimination technique (MIGET) were compared in the evaluation of the contribution of low alveolar ventilation-perfusion ratio (VA/Q) lung regions (0.005 less than VA/Q less than 0.1) to venous admixture (Qva/QT). The arterial-alveolar N2 difference was determined using a manometric technique for the measurement of the arterial N2 partial pressure (PN2). We adopted a two-compartment model of the lung, one compartment having a VA/Q of approximately 1, the other being open, gas filled, unventilated (VA/Q = 0), and in equilibrium with the mixed venous blood. This theoretical single compartment represents all lung regions responsible for the arterial-alveolar N2 difference. The fractional blood flow to this compartment was calculated using an appropriate mixing equation (Q0/QT). There was a weak but significant relationship between Q0/QT and the perfusion fraction to lung regions with low VA/Q (0.005 less than VA/Q less than 0.1) (r = 0.542, P less than 0.05) and a close relationship between Q0/QT and the perfusion fraction to lung regions with VA/Q ratios less than 0.9 (r = 0.862, P less than 0.001) as obtained from MIGET. The difference Qva/QT-Q0/QT yielded a close estimation of the MIGET right-to-left shunt (Qs/QT) (r = 0.962, P less than 0.001). We conclude that the assessment of the arterial-alveolar N2 difference and Q0/QT does not yield a quantitative estimation of the contribution of pathologically low VA/Q areas to QVa/QT because these parameters reflect an unknown combination of pathological and normal (0.1 less than VA/Q less than 0.9) gas exchange units.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement of gas exchange during inhibition of hypoxic pulmonary vasoconstriction by nitrendipine in piglets.

To determine how nitrendipine (N), a calcium antagonist, interferes with haemodynamics and gas exchange during hypoxia, we studied 12 piglets (4-6 weeks, 4.3-9.0 kg) anaesthetized with pentobarbital (20 mg.kg-1 i.p.). Haemodynamics, blood gases and multiple inert gas elimination were measured at the end of three consecutive 30 min periods of spontaneous breathing: room air (RA), 11-12% FIO2 (H) and 11-12% FIO2 with a randomly selected infusion of N (3 micrograms.kg-1.min-1) (HN) or the carrier solution (HP) (6 animals in each group). Pulmonary vascular resistance (Rpv) doubled from 8.7 +/- 2.8 mmHg.min-1.1-1 in RA to 19.5 +/- 10.0 (mean +/- SD) in H while PaO2 fell from 83 +/- 8.3 mmHg to 28.7 +/- 5.2. With N, Rpv fell back to room air value: 8.7 +/- 2.0 (p less than 0.02; comparison H and HN), while PaO2 rose from 29.3 +/- 6.3 mmHg in H to 46.1 +/- 6.1 HN (p less than 0.001) and PaCO2 fell from 33.8 +/- 10 to 23.9 +/- 3.7 mmHg. There was a small non-significant rise in VE. Haemodynamics and blood gases of the placebo group were not statistically different in H and HP. No extrapulmonary shunting was evidenced during any experimental period. The perfusion to lung zones with VA/Q lower than 0.005 rose from 1.1 +/- 2.1% in RA to 8.9 +/- 5.7% in H, but no further increase was obtained with N: 5.1 +/- 2.5%. Overall VA/Q matching did not deteriorate with N during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic sodium cyanate treatment induces "hypoxia-like" effects in rats.

Three weeks of sodium cyanate (NaCNO) intraperitoneal treatment in rats (n = 15) induced high hemoglobin O2 affinity, i.e., low PO2 at 50% hemoglobin saturation (P50), 20.5 +/- 1.4 Torr, in comparison with the mean control values, 34.5 +/- 1.6 Torr (n = 15). NaCNO rats showed a reduction in mean body weight, 376 +/- 27 g, in comparison with controls, 423 +/- 23 g (P less than 0.001). Despite arterial O2 partial pressure (PaO2) within normal limits NaCNO-treated rats had a higher systolic right ventricular pressure (SRVP), 33.7 +/- 3.1 Torr, in comparison with control value, 29.0 +/- 2.5 Torr (P less than 0.001). Right ventricle weights were significantly increased (P less than 0.001). After 60 min of an hypoxic challenge (fractional concentration of inspired O2 = 0.10) NaCNO-treated rats increased SRVP of only 7 +/- 4% compared with 46 +/- 9% in the control animals. Inducing high hemoglobin affinity in rats (n = 10; 6 wk NaCNO treatment) resulted in increases in hematocrit ratio and hemoglobin concentration (P less than 0.001). The characteristics of the red blood cell (RBC) itself changed; values of mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration being significantly increased (P less than 0.001) when compared with mean control values. The count of nucleated RBC's appeared to be significantly higher from the 2nd wk of NaCNO treatment. Chronic NaCNO treatment was demonstrated to exert "hypoxia-like" effects since it induced prevention of normal growth, polycythemia, pulmonary hypertension, right ventricular hypertrophy, and blunted pulmonary pressor response to acute hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological effects of high-P50 erythrocyte transfusion on piglets.

Rightward shifts of the O2 dissociation curve (ODC) were experimentally obtained in lysed and resealed erythrocytes following encapsulation of inositol hexaphosphate (IHP). This continuous lysing and resealing procedure led to in vitro P50 (Po2 at 50% hemoglobin saturation) increases up to 80 Torr (pH, 7.40; Pco2, 40 Torr; temp, 37 degrees C) for both human and pig erythrocytes. The Hill number of the transformed blood decreased when IHP was fixed on the hemoglobin, but the sigmoid shape of the ODC was maintained. The O2 hemoglobin binding capacity and the mean corpuscular hemoglobin content were found unchanged by the experimental procedure in human and pig erythrocytes. Isovolumic exchange transfusion of high-P50 erythrocytes in anesthetized and ambient air-ventilated piglets (n = 6) led to substantial in vivo P50 increases (range, 8-19 Torr). The rightward shift of the ODC was concomitant with an increase of the arterial Po2 and of the arteriovenous O2 content difference, 19 and 59% respectively above their control values. The mixed-venous Po2 (PVO2) remained unchanged. The cardiac output was shown to be inversely related to the P50 value. In spite of the O2-transport reduction (37%), O2 consumption was maintained due to enhanced O2 extraction.

Induced low P50 in anesthetized rats: blood gas, circulatory and metabolic adjustments.

In anesthetized, normoxic or hypoxic rats the hemodynamic, metabolic and O2 transport characteristics following exchange transfusion with human erythrocytes containing a high O2 affinity hemoglobin (Hemoglobin Creteil, beta 89 Ser----Asp) have been studied. The in vivo oxygen partial pressure at 50% oxygen hemoglobin saturation (P50) decreased from 37.4 +/- 2.1 to 12.7 +/- 0.7 mm Hg; the arterial oxygen tension was reduced significantly from 109.9 +/- 7.7 to 87.3 +/- 12.0 mm Hg. There was a decrease in right ventricular partial pressure of oxygen (PvO2), (P less than 0.001), oxygen consumption (VO2), (P less than 0.001), arterio-venous difference, (P less than 0.001), and peripheral vascular resistance index, (P less than 0.01). Exchange transfusion with normal rat blood (P50 = 37.2 +/- 2.4 mm Hg) or with 2,3-diphosphoglycerate-enriched human red blood cells (P50 = 34.7 +/- 2.2 mm Hg), did not modify these variables in normoxic rats. In hypoxia, the reduction in P50 was associated with a further decrease in PvO2 an increase in serum lactate concentration and a VO2 decrease.

Po2 temperature blood factor for blood gas apparatus.

PO2 temperature formulae supplied by manufacturers on automatic blood gas apparatus, PO2 corr. = PO2 37 degrees C X 10F X delta T were studied and compared to the experimental determination of the delta log PO2/delta T ratio (Hérigault et al. [10]). Acid-base status at 37 degrees C appeared to have a measurable influence on the PO2 temperature factor; alkalosis increased the delta log PO2/delta T ratio, and the contrary was found for acidosis in comparison with normal acid-base status at 37 degrees C. For the same PO2, measured at 37 degrees C, all the proposed formulae of commercial blood gas automatic apparatus did not give the same temperature corrected PO2. The observed difference between the corrected PO2 may be important and greater than the precision of the initial measurement. To correct the measured PO2 for temperature, a relationship between delta log PO2/delta T and PO2 is proposed, between PO2 zero and PO2 180 mmHg, which takes into account measured pH and PO2 values at 37 degrees C:delta log PO2/delta T = [(-0.35 pH + 0.658) X 10(-4) X PO2] + 0.035.

Determination of the PO2 temperature blood factor from oxygen dissociation curves.

The variation with saturation of the temperature coefficient of PO2 in human blood (delta log PO2/delta T) was determined by continuous recording of the oxygen dissociation curve (ODC), at 37 degrees C and 25 degrees C, on the same blood samples. PCO2 and pH were held constant through an ODC run, and PCO2 was reduced at 25 degrees C to the value measured by anaerobic cooling of the same sample. delta log PO2/delta T was calculated from isosaturation points on the 37 and 25 degrees C curves. The temperature coefficient was also computed as an independent check on this method by determination of the effects of temperature (25, 30, 37 and 40 degrees C) on hemoglobin ligand interaction: fixed acid Bohr effect (delta log PO2/delta pH), carbamino-formation (delta log PO2/delta log PCO2) and hemoglobin oxygen affinity. The values of delta log PO2/delta T ratio obtained from the two different approaches were found to be in good agreement. The coefficient decreased when [H+] concentration was increased. A linear relationship between the Bohr factor and the temperature was found: delta log PO2/delta pH = 0.00267 T-0.520 (r = 0.85; n = 40) At 25 degrees C, the carbamino-formation was one order of magnitude lower than at 37 degrees C. Acid-base state and saturation value appeared to be major determinant factors for the temperature correction coefficient to be applied to blood PO2 values measured at standard (37 degrees C) temperature.

[Contamination of an oxygen delivery circuit by compressed air]. / Contamination d'un circuit d'oxygène par de l'air comprimé.

Routine checking of the FIO2 of a mixture delivered by a ventilator revealed large discrepancies between the FIO2 assigned and that effectively delivered, the latter being low. Measurements of FIO2 at the wall outlets showed the O2 delivery pipeline to be contaminated by compressed air. By disconnecting all the ventilators supplied by this pipeline one after the other, one ventilator, or rather its blender, was found responsible.

Consequences of an acute increase in P50 in anaesthetized guinea pigs.

In anaesthetized guinea pigs, ventilated with ambient air, the peripheral haemodynamics and oxygen transport characteristics have been studied following a blood exchange transfusion with rat erythrocytes suspended in guinea pig plasma. Since the rat haemoglobin exhibited a lower oxygen affinity than guinea pig haemoglobin, the oxygen partial pressure at 50% of oxygen haemoglobin saturation (P50) increased from 25.2 +/- 1.1 to 37.2 +/- 0.9 mm Hg (n = 10). This increase in P50 was accompanied by a significant increase in arterial oxygen partial pressure (PaO2) and in arterio-venous difference (AVDO2). Cardiac output (Q) was decreased significantly, but oxygen consumption (VO2) remained within control values. The increase in P50 was associated with a venous oxygen partial pressure (P-VO2) which remained constant but an increase in blood lactate concentration was observed. Control exchange transfusion with fresh guinea pig blood had no effect on acid-base status, on oxygen transport, or on peripheral resistance. The sudden reduction in haemoglobin oxygen affinity induced an increase in peripheral resistance with a decrease in cardiac output, the arterial systemic pressure being maintained. These results suggested that an acute decrease in haemoglobin oxygen affinity was compensated for by a simultaneous diminution of overall tissue blood flow and reduction of capillary recruitment.