The oxyhemoglobin dissociation curve in liver cirrhosis.

STUDY OBJECTIVES: To trace the entire oxyhemoglobin dissociation curve (ODC) in a cohort of cirrhotic patients in stable condition who were candidates for orthotopic liver transplantation (OLT). DESIGN: Prospective cohort study. SETTING: A large academic hospital. PATIENTS AND METHODS: We traced the entire ODC in whole blood in standard conditions (pH 7.4; PCO2, 40 mm Hg; temperature, 37 degrees C) for 50 cirrhotic candidates for OLT (27 men and 23 women) and 50 age- and height-matched healthy subjects (27 men and 23 women). All subjects were nonsmokers or ex-smokers for at least 5 years. We also measured 2,3 diphosphoglycerate (2,3 DPG) in RBCs, plasma ions, and arterial blood gases in all subjects according to standard methods. Mixed venous blood was also obtained from the 50 cirrhotic patients. RESULTS: Mean ODC was the same in the two groups. However, for the cirrhotic patients, the dispersion of the PO2 values of oxygen saturation percentage (SO2%) from 20 to 80% was significantly larger (p < 0.01 to p < 0.0001). In the cirrhotic patients, the mean PO2 for half-saturation of hemoglobin (P50) was 7.11 + 0.14 mEq/L chloride (p < 0.001) plus 0.36 mEq/L inorganic phosphate (p < 0.05) plus 0.25 micromol/gram of hemoglobin (gHb) 2,3 DPG (p < 0.00002) in absolute numerical values. Sodium, potassium, and calcium, three plasma ions disturbed in cirrhotic patients, did not contribute to determine the mean P50. DISCUSSION: In patients with cirrhosis, increased dispersion of PO2 values for a given level of SO2% may be related to four factors: (1) an observed alteration of the enzymes controlling the phosphoglycerate shunt; (2) hypothyroidism, which may affect 7 to 20% of patients with primary biliary cirrhosis; (3) the type of ongoing treatment, eg, diuretics and/or propranolol; and (4) plasma ion disturbances. CONCLUSIONS: We describe the ODC by three indexes: shape, position, and an index of dispersion of the PO2 values for a given level of SO2%. In addition, when the latter is increased, we suggest that other factors than pH, temperature, carbon dioxide, and inorganic phosphates are acting on the position of the ODC.

Comparative effects of helium-oxygen and external positive end-expiratory pressure on respiratory mechanics, gas exchange, and ventilation-perfusion relationships in mechanically ventilated patients with chronic obstructive pulmonary disease.

OBJECTIVE: To compare the effects of He/O(2) and external PEEP (PEEPe) on intrinsic PEEP (PEEPi), respiratory mechanics, gas exchange, and ventilation/perfusion (V(A)/Q) in mechanically ventilated COPD patients. DESIGN AND SETTING: Prospective, interventional study in the intensive care unit of a university hospital. INTERVENTIONS: Ten intubated, sedated, paralyzed, mechanically ventilated COPD patients studied in the following conditions: (a) baseline settings made by clinician in charge, air/O(2), ZEEP; (b) He/O(2), ZEEP; (c) air/O(2), ZEEP; (d) air/O(2), PEEPe 80% of PEEPi. Measurements at each condition included V(A)/Q by the multiple inert gas elimination technique (MIGET). RESULTS: PEEPi and trapped gas volume were comparably reduced by He/O(2) (4.2+/-4 vs. 7.7+/-4 cmH(2)O and 98+/-82 vs. 217+/-124 ml, respectively) and PEEPe (4.4+/-1.3 vs. 7.8+/-3.6 cmH(2)O and 120+/-107 vs. 216+/-115 ml, respectively). He/O(2) reduced inspiratory and expiratory respiratory system resistance (15.5+/-4.4 vs. 20.7+/-6.9 and 19+/-9 vs. 28.8+/-15 cmH(2)O l(-1)s(-1), respectively) and plateau pressure (13+/-4 vs. 17+/-6 cmH(2)O). PEEPe increased airway pressures, including total PEEP, and elastance. PaO(2)/FIO(2) was slightly reduced by He/O(2) (225+/-83 vs. 245+/-82) without significant V(A)/Q change. CONCLUSIONS: He/O(2) and PEEPe comparably reduced PEEPi and trapped gas volume. However, He/O(2) decreased airway resistance and intrathoracic pressures, at a small cost in arterial oxygenation. He/O(2) could offer an attractive option in COPD patients with PEEPi/dynamic hyperinflation.

Effects of helium-oxygen on respiratory mechanics, gas exchange, and ventilation-perfusion relationships in a porcine model of stable methacholine-induced bronchospasm.

OBJECTIVE: To explore the consequences of helium/oxygen (He/O(2)) inhalation on respiratory mechanics, gas exchange, and ventilation-perfusion (VA/Q) relationships in an animal model of severe induced bronchospasm during mechanical ventilation. DESIGN: Prospective, interventional study. SETTING: Experimental animal laboratory, university hospital. INTERVENTIONS: Seven piglets were anesthetized, paralyzed, and mechanically ventilated, with all ventilator settings remaining constant throughout the protocol. Acute stable bronchospasm was obtained through continuous aerosolization of methacholine. Once steady-state was achieved, the animals successively breathed air/O(2) and He/O(2) (FIO(2) 0.3), or inversely, in random order. Measurements were taken at baseline, during bronchospasm, and after 30 min of He/O(2) inhalation. RESULTS: Bronchospasm increased lung peak inspiratory pressure (49+/-6.9 vs 18+/-1 cm H(2)O, P<0.001), lung resistance (22.7+/-1.5 vs 6.8+/-1.5 cm H(2)O x l(-1).s, P<0.001), dynamic elastance (76+/-11.2 vs 22.8+/-4.1 cm H(2)O x l(-1), P<0.001), and work of breathing (1.51+/-0.26 vs 0.47+/-0.08, P<0.001). Arterial pH decreased (7.47+/-0.06 vs 7.32+/-0.06, P<0.001), PaCO(2) increased, and PaO(2) decreased. Multiple inert gas elimination showed an absence of shunt, substantial increases in perfusion to low VA/Q regions, and dispersion of VA/Q distribution. He/O(2) reduced lung resistance and work of breathing, and worsened hypercapnia and respiratory acidosis. CONCLUSIONS: In this model, while He/O(2) improved respiratory mechanics and reduced work of breathing, hypercapnia and respiratory acidosis increased. Close attention should be paid to monitoring arterial blood gases when He/O(2) is used in mechanically ventilated acute severe asthma.

An improved porcine model of stable methacholine-induced bronchospasm.

OBJECTIVE: To validate an animal model replicating the pathophysiological characteristics of severe induced bronchospasm observed in humans, with a high level of stability permitting measurements such as the assessment of ventilation-perfusion relationships with the multiple inert gas elimination technique. DESIGN AND SETTING: Experimental study in an animal research laboratory. SUBJECTS: 13 piglets (age 3-4 months) were studied and 7 underwent the complete protocol INTERVENTIONS: The animals were anesthetized and paralyzed. Mechanical ventilation was initiated in a volume-controlled mode. Ventilatory parameters were adjusted to obtain normocapnia and were maintained constant during the bronchospasm. Methacholine was administered via a synchronized nebulizer and progressively adjusted to obtain a stable twofold increase in peak inspiratory pressure. MEASUREMENTS AND RESULTS: Cardiopulmonary physiological data including assessment of lung mechanics and measurement of ventilation-perfusion relationships were obtained before and during the bronchospasm. Peak inspiratory pressure increased from 19.7+/-2.9 to 44.4+/-7.1 cmH(2)O during the bronchospasm. The latter remained stable over 2 h. Respiratory mechanics, gas exchange, and ventilation-perfusion distribution changes typical of those observed in severe bronchospasm in humans were observed in all animals. CONCLUSIONS: The present experimental model replicates some of the physiopathological characteristics of severe human bronchospasm, and its stability should facilitate studies of the effects of different ventilatory modes in the setting of acute severe asthma.

Mechanisms controlling the oxygen consumption in experimentally induced hypochloremic alkalosis in calves.

The study was carried out on healthy Friesian calves (n = 10) aged between 10 and 30 days. Hypochloremia and alkalosis were induced by intravenous administration of furosemide and isotonic sodium bicarbonate. The venous and arterial blood samples were collected repeatedly. 2,3-diphosphoglycerate (2,3-DPG), hemoglobin and plasmatic chloride concentrations were determined. The red blood cell chloride concentration was also calculated. pH, PCO2 and PO2 were measured in arterial and mixed venous blood. The oxygen equilibrium curve (OEC) was measured in standard conditions. The correspondence of the OEC to the arterial and mixed venous compartments was calculated, taking blood temperature, pH and PCO2 values into account. The oxygen exchange fraction (OEF%), corresponding to the degree of blood desaturation between the arterial and mixed venous compartments and the amount of oxygen released at the tissue level by 100 mL of blood (OEF Vol%) were calculated from the arterial and mixed venous OEC, combined with PO2 and hemoglobin concentration. Oxygen delivery (DO2) was calculated using the arterial oxygen content, the cardiac output measured by thermodilution, and the body weight of the animal. The oxygen consumption (VO2) was derived from the cardiac output, OEF Vol% and body weight values. Despite the plasma hypochloremia, the erythrocyte chloride concentration was not influenced by furosemide and sodium bicarbonate infusion. Due to the alkalosis-induced increase in the 2,3-DPG, the standard OEC was shifted to the right, allowing oxygen to dissociate from hemoglobin more rapidly. These changes opposed the increased affinity of hemoglobin for oxygen induced by alkalosis. Moreover, respiratory acidosis, hemoconcentration, and the slight decrease in the partial oxygen pressure in mixed venous blood (Pvo2) tended to improve the OEF Vol% and maintain the oxygen consumption in a physiological range while the cardiac output, and the oxygen delivery were significantly decreased. It may be concluded that, despite reduced oxygen delivery, oxygen consumption is maintained during experimentally induced hypochloremic alkalosis in healthy 10-30 day old calves.

Blood oxygen binding in hypoxaemic calves.

Blood oxygen transport and tissue oxygenation were studied in 28 calves from the Belgian White and Blue breed (20 healthy and 8 hypoxaemic ones). Hypoxaemic calves were selected according to their high respiratory frequency and to their low partial oxygen pressure (PaO2) in the arterial blood. Venous and arterial blood samples were collected, and 2,3-diphosphoglycerate, adenosine triphosphate, chloride, inorganic phosphate and hemoglobin concentrations, and pH, PCO, and PO2 were determined. An oxygen equilibrium curve (OEC) was measured in standard conditions, for each animal. The arterial and venous OEC were calculated, taking body temperature, pH and PCO2 values in arterial and venous blood into account. The oxygen exchange fraction (OEF%), corresponding to the degree of blood desaturation between the arterial and the venous compartments, and the amount of oxygen released at the tissue level by 100 mL of blood (OEF Vol%) were calculated from the arterial and venous OEC combined with the PO2 and hemoglobin concentration. In hypoxaemic calves investigated in this study, the hemoglobin oxygen affinity, measured under standard conditions, was not modified. On the contrary, in vivo acidosis and hypercapnia induced a decrease in the hemoglobin oxygen affinity in arterial blood, which combined to the decrease in PaO2 led to a reduced hemoglobin saturation degree in the arterial compartment. However, this did not impair the oxygen exchange fraction (OEF%), since the hemoglobin saturation degree in venous blood was also diminished.