Severe hypoxemia and liver disease

Severe hypoxemia and orthodeoxia in patients with chronic liver disease is uncommon, but, when present, it is incapacitating. The purpose of this study was to determine the distribution of alveolar ventilation-perfusion (VA/Q) in six patients with mild liver disease and severe hypoxemia (PaO2 at rest in sitting or standing position ranged from 35 to 67 mm Hg). Orthodeoxia was documented with improvement in PaO2 in the supine position in each patient (PaO2 at rest in supine position ranged from 46 to 75 mm Hg). VA/Q distribution was measured by the multiple inert gas elimination technique. The dispersion of VA/Q was increased with small portions of the cardiac output (0.5 to 14.8%) perfusing low VA/Q areas (O less than VA/Q less than 0.1). Another major finding was a large right-to-left shunt (VA/Q less than 0.005) that ranged from 4 to 28%. The VA/Q mismatching and the right-to-left shunt both contributed to the hypoxemia. The predicted PaO2 was 5.5 mm Hg (p less than 0.01) larger than the measured PaO2. In each patient, the mean pulmonary artery pressure was low and the cardiac output was elevated. These results show that the low PaO2 in these patients was due to both increased right-to-left shunt and VA/Q mismatching, but impaired diffusion could not be ruled out.     

Pulmonary and extrapulmonary contributors to hypoxemia in liver cirrhosis

To determine and to quantify the pulmonary and extrapulmonary contributors to hypoxemia in liver cirrhosis, we measured in 10 cirrhotics blood gases, P50, hemodynamics, ventilation, and the distribution of ventilation-perfusion ratios (VA/Q) using the multiple inert gas elimination technique. Seven patients had an arterial hypoxemia (PaO2 = 69 +/- 6 mm Hg, mean +/- SD), and three patients were normoxemic (PaO2 = 89 +/- 6 mm Hg). In each hypoxemic patient, the VA/Q distributions were characterized by the presence of low VA/Q units. A negative logarithmic correlation was found between the dispersion of the blood flow distribution and the arterial PO2. An acute inspiratory hypoxia (FIO2, 0.125) elicited an increase in pulmonary vascular resistance by 58.5% in the hypoxemic group and by 81.6% in the normoxemic one (p = NS between the two groups). The percent change in pulmonary vascular resistance induced by hypoxia was not correlated with the percent change in the dispersion of the blood flow distribution. A theoretical analysis showed that the mean arterial PO2 of 69 mm Hg of the hypoxemic group differed from a normal reference value of 96 mm Hg as a result of the combined effects of reduced hemoglobin (-4 mm Hg), increased P50 (+4 mm Hg), increased ventilation (+10 mm Hg), low VA/Q (-35 mm Hg), and true shunt (-2 mm Hg). These results show that the "hypoxemia of liver cirrhosis" is essentially caused by VA/Q mismatching, which is not explained by an abnormal hypoxic pulmonary vasoconstriction.     

Gas exchange and pulmonary vascular reactivity in patients with liver cirrhosis

To investigate the mechanisms underlying abnormal gas exchange in liver cirrhosis, 15 patients were studied while breathing room air, 11% O2, and 100% O2 in random sequence. Under basal conditions, patients showed mild reductions from normal in systemic and pulmonary vascular resistance, normal PaO2 (mean, 92.5 +/- 2.5 mm Hg), mild hypocapnia (mean, 34 +/- 0.7 mm Hg), and a slightly right-shifted oxyhemoglobin dissociation curve (P50, 27.2 +/- 0.4 mm Hg; 2,3-DPG, 13.1 +/- 0.6 mumol/g). Using the multiple insert gas elimination technique, we found mild to moderate ventilation-perfusion (VA/Q) inequality with a mean of 5% (range, 0 to 20%) of cardiac output (QT) perfusing low VA/Q ratio (less than 0.1) areas but no shunt. Breathing 11% O2, there were significant increases in QT, pulmonary artery pressure, and vascular resistance, whereas no changes occurred in VA/Q distribution, and there was no evidence for alveolar-endcapillary diffusion limitation for O2. In contrast, after 100% O2 shunt developed and VA/Q relationships worsened without significant hemodynamic changes. Furthermore, patients with cutaneous spider nevi (n = 8) showed more hepatocellular dysfunction (lower prothrombin values), lower systemic and pulmonary vascular resistance, less hypoxic pulmonary vasoconstriction (HPV), lower PaO2, and more VA/Q mismatch than did those without spiders. Our results confirm, therefore, that HPV is not fully abolished, as previously described, in hepatic cirrhosis. However, those patients with more advanced hepatic disease exhibit inadequate pulmonary vascular tone, which increases VA/Q inequality and lowers PaO2.     

Mechanisms of hypoxemia in patients with status asthmaticus requiring mechanical ventilation

Eight consecutive patients (mean +/- SD age, 43 +/- 11 yr) with acute severe asthma (status asthmaticus) requiring assisted ventilation were studied within the first 24 to 48 h of admission, at maintenance FIO2 and while breathing 100% O2, using the multiple inert gas elimination technique. Ventilation-perfusion (VA/Q) inequality was characterized by a marked bimodal blood flow distribution (perfusion to normal and low VA/Q populations) in all but two patients, with a mean of 27.6 +/- 12.3% of the total perfusion present in the low VA/Q ratio units (between 0.1 and 0.005). As a result, the dispersion of pulmonary blood flow distribution (log SDQ) was severely abnormal (mean, 1.65 +/- 0.28; normal range, 0.3 to 0.6). No patient had a substantial shunt (VA/Q = 0) (mean value, 1.5 +/- 2.3%). The ventilation distribution was never bimodal, but the dispersion of the ventilation distribution (log SDV) was moderately elevated (1.01 +/- 0.24). High VA/Q areas (ventilation to VA/Q units between 10 and 100) were generally absent. While breathing 100% O2, PaO2, PvO2, and PaCO2 significantly rose, as did shunt and blood flow dispersion. Patients with life-threatening acute severe asthma treated by mechanical ventilation show: (1) the most abnormal gas exchange characteristics of the VA/Q spectrum observed to date in human asthma but essentially the same pattern as in patients with less severe disease; (2) a high level of hypoxic pulmonary vascular response; (3) a significant amount of shunt while breathing 100% O2, suggesting the presence of absorption atelectasis or redistribution of blood flow.     

Ventilation-perfusion relationships during exercise-induced asthma in children

In order to elucidate the mechanisms underlying the hypoxemia associated with exercise-induced asthma (EIA), ventilation-perfusion (VA/Q) relationships were investigated in 11 children with a history of EIA. A virtually continuous distribution of VA/Q ratios was measured by the multiple inert gas technique with the children at rest before and after an exercise test. All children displayed a unimodal distribution before the test. In 4 of the children, the exercise test did not provoke asthma, and the unimodal (VA/Q) distribution was maintained. Of the 7 children who developed asthma, 6 displayed a bimodal distribution. One mode fell within normal VA/Q regions but with increased perfusion to regions with VA/Q ratios of 0.1 to 1, which correlated well to the hypoxemia noted during asthma. The other mode fell within regions with high VA/Q ratios, and the magnitude of the mode correlated to the reduction in FEV1 and PaO2. No one had a shunt or a clearly low VA/Q mode (VA/Q less than 0.1). We hypothesize that the high VA/Q was caused by increased intrathoracic pressure impeding regional blood flow.     

Hemodynamic disturbances and VA/Q matching in hypoxemic cirrhotic patients

Arterial oxygen desaturation is commonly found in patients with cirrhosis of the liver, but severe hypoxemia is unusual. To investigate the mechanism of the impairment in gas exchange, six severely hypoxemic (mean PaO2, 55.9 +/- 5.9 mm Hg) cirrhotic patients (five confirmed by biopsy), without pulmonary or cardiovascular disease and in the absence of acute hepatic disease, were submitted to right heart catheterization. Inequalities of VA/Q were estimated in the respiratory steady state using the multiple inert gas technique. The mean pulmonary arterial pressure was low (7.2 +/- 2.3 mm Hg) and the cardiac output high (Q = 11.0 +/- 2.06 L/min), indicating a low PVR. The VA/Q mismatching of the ventilated and perfused units ranged from mild to moderate, but a large percentage of Q flowed through unventilated areas. Furthermore, there was a significant difference between predicted and measured PaO2 (9.27 +/- 5.9 mm Hg; p less than 0.01), which was attributed to either an unmeasured postpulmonary shunt (between portal and pulmonary vein) or a diffusion defect. The impairment in gas exchange in these patients is thus due primarily to an intrapulmonary, and possibly extrapulmonary, shunt. This was thought to be due mainly to an impaired regulatory mechanism of the microcirculation by the hepatic dysfunction.     

Pulmonary hemodynamics and gas exchange during exercise in liver cirrhosis

We have recently shown that ventilation-perfusion (VA/Q) mismatching at rest in cirrhosis is due to an abnormal pulmonary vascular tone. It has been suggested that in patients with cirrhosis, O2 transfer might become diffusion-limited during exercise. This study examined pulmonary hemodynamics and mechanisms modulating gas exchange during exercise (60 to 70% VO2max) in six patients (41 +/- 5 yr, mean +/- SEM) with cirrhosis but with normal lung function tests. At rest, QT was high (8.4 +/- 0.5 L/min), pulmonary vascular resistance (PVR) was low (0.61 +/- 0.17 mm Hg/L/min), and there was mild to moderate VA/Q mismatching (LogSD Q, 0.79 +/- 0.09; normal range, 0.3 to 0.6). However, hyperventilation (PaCO2, 29 +/- 2 mm Hg) and high QT (thus, high PVO2, 41 +/- 2 mm Hg) contributed to the maintenance of PaO2 within normal values (99 +/- 7 mm Hg). Exercise VO2 (1,278 +/- 122 ml/min) was normal relative to work load, but, contrary to that in normal subjects, QT was higher and PVR did not fall. During exercise, PaO2 showed a trend to decrease (to 90 +/- 5 mm Hg) and PaCO2 to rise (to 35 +/- 2 mm Hg), but the differences failed to reach statistical significance (p = 0.07 each). PVO2 fell significantly with exercise (41 +/- 2 to 33 +/- 0.3 mm Hg, p less than 0.05), but neither AaPO2 (15 +/- 7 to 21 +/- 6 mm Hg) nor VA/Q inequality (LogSD Q, 0.82 +/- 0.11) changed. No systemic difference was noticed between predicted and measured PaO2 values, suggesting no O2 diffusion impairment during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Relationship Between Severity of Liver Cirrhosis and Pulmonary Function Tests

Pulmonary complications, mainly hepatopulmonary syndrome (HPS), are frequently observed in liver cirrhosis. In this study, the aim was to investigate the frequency of hypoxemia and impairment of pulmonary function tests (PFT) in patients with liver cirrhosis and to examine the relationships of these impairments with liver failure. A total of 39 patients with cirrhosis, 24 males and 15 females, were included in our study. The mean age of the patients was 47.5 +/- 17.2 years. Arterial blood gases, PFT, and carbon monoxide diffusion tests (DLCO) were performed in all patients. Out of 39 cirrhotic patients, 21 (53.8%) had ascites, whereas 18 (46.2%) did not. Seven patients were in the Child-Pugh A group, 21 in the Child-Pugh B group, and 11 patients were in the Child-Pugh C group. Hypoxia was found in 33.3% of the patients. Although the PaO2 and SaO2 values of patients with ascites were lower compared to those without ascites (P < 0.05), no statistically significant difference was determined in the comparison of hypoxia between the groups (P > 0.05). Among the PFT parameters, FEV1/FVC and FEF25-75% values were found to be lower in patients with ascites than those without (P < 0.05). No differences were established between these two groups of patients in terms of DLCO (P > 0.05). While no differences were found in comparison of the DLCO values in between the groups (P > 0.05), there was a statistically significant difference in the ratio of DLCO to the alveolar ventilation (DLCO/VA) in between the groups (P < 0.05). On the other hand, a negative correlation was found between the DLCO/VA and Child points when the relationship between the Child-Pugh score and PFT parameters were investigated (r = -0.371, P < 0.05). Consequently, a relationship was established between the severity of liver failure and diffusion tests showing pulmonary complications invasively. We believe diffusions tests should be performed in addition to the PFT in order to determine pulmonary involvements particularly in patients who are candidates for liver transplantation.     

Distribution of ventilation-perfusion ratios in pneumonectomized dogs

In this paper, the distribution of ventilation (VA) and of pulmonary perfusion (Q), gas exchanges, and the single breath CO diffusing capacity are measured in 8 dogs before and after left pneumonectomy. During surgery 4 dogs, in which the left pulmonary artery is clamped, and 4 other dogs in which the left mainstem bronchus is clamped, are studied. A minute ventilation (VE) is adjusted during the initial stage in each dog but it is kept constant for the other stages. For the entire group of dogs, the overall VE/Q varies from 0.8 to 3.0 in the baseline study. In the initial study, the perfusion distribution is unimodal and the ventilation distribution is unimodal or bimodal. The percentage of ventilation of the second mode correlates approximately with the overall VA/Q. After clamping the left pulmonary artery, the correlation between overall VA/Q, capillary shunt, and blood gases data is excellent and the ventilation and perfusion distributions are both bimodal. One perfusion mode is situated in the low VA/Q ratios while one ventilation mode is situated in the high VA/Q ratios. After clamping the left mainstem bronchus, the average anatomical shunt is 27%, the ventilation and perfusion are both bimodal, and the mean PaO2 is 55 mm Hg. Ultimately the ventilation and perfusion distributions tend to return to normal after pneumonectomy.     

Distribution of ventilation and perfusion during positive end-expiratory pressure in the adult respiratory distress syndrome

The response of respiratory gas exchange to incremental increases in positive end-expiratory pressure (PEEP) was studied in patients with the adult respiratory distress syndrome (ARDS). Fifty total changes in PEEP were studied in 19 PEEP trials performed in 16 patients. The initial patterns of ventilation-perfusion distribution as measured by the multiple inert gas elimination technique showed a large shunt flow (32 +/- 14% of total cardiac output), which was accompanied in half of the patients by perfusion to a region of low ventilation-perfusion ratio (VA/Q ratio less than 0.1). In 17 PEEP trials, there was an improvement in PaO2 (increase in PaO2 greater than 10 mmHg over control value) with at least one level of PEEP tested. In the 38 PEEP increments in these trials where PaO2 did improve, there was either a reduction in shunt alone, a reduction in ventilation-perfusion regions alone, or a redistribution in blood flow from shunt to regions of low or normal ventilation-perfusion ratio. In the increments where no increase was observed in PaO2, this reduction in blood flow to shunt or low VA/Q regions did not occur. In some instances, there was an increase in ventilation to unperfused alveoli and evidence of high ventilation-perfusion ratio (VA/Q greater than 10) as the level of PEEP increased. Because patients had an adequate pulmonary artery wedge pressure at the start of the PEEP trial (mean wedge pressure, 12.8 +/- 1.5 mmHg) improvements in oxygenation could usually be attained with only mild decreases in cardiac output.     

The relationship between pulmonary function tests, thorax HRCT, and quantitative ventilation-perfusion scintigraphy in chronic obstructive pulmonary disease

We have evaluated the relationship between pulmonary function tests (PFT), thorax high resolution computed tomography (HRCT) images and quantitative ventilation-perfusion (V/Q) scintigraphic studies in 16 male patients (mean age 65.6 +/- 5.5 years) with chronic obstructive pulmonary disease (COPD). The mean forced vital capacity (FVC) value of the patient group was 2352 +/- 642 mL (65.4 +/- 15.8%), whereas mean forced expiratory volume in one second (FEV(1)) was found to be 1150 +/- 442 mL (40.8 +/- 14.9%). The ratio of carbon monoxide diffusion capacity to alveolar ventilation (DLCO/VA) was 3.17 +/- 0.88 mL/min/mmHg/L, and the mean partial oxygen (PaO(2)) and carbon dioxide (PaCO(2)) pressures were 68.5 +/- 11.04 mmHg and 38.9 +/- 5.8 mmHg respectively. For each patient, thorax HRCT and V/Q scintigraphic images of both lungs were divided into upper, mid and lower zones during examination. Visual scoring for the assessment of emphysema on thorax HRCT were used and images were graded from mild to severe (< or = 25% - > or = 76%). Emphysema scores were found to be higher on upper zones with accompanying lowest V/Q ratios. DLCO/VA, DLCO, total emphysema scores, and individual emphysema scores of the upper, mid and lower zones were found to be correlated. As a conclusion, it can be stated that emphysematous changes in COPD patients are more apparent in the upper lung zones, which also have the lowest V/Q ratios.     

Effect of almitrine on ventilation-perfusion distribution in adult respiratory distress syndrome

Almitrine improves ventilation/perfusion relationships (VA/Q) in COPD, but its effects in ARDS, in which VA/Q mismatching is the cause of severe hypoxemia, are not known. The effects of almitrine on pulmonary gas exchange and circulation were assessed in 9 patients with ARDS who were sedated, paralyzed, and mechanically ventilated at constant FlO2 (range, 0.48 to 0.74). Systemic and pulmonary hemodynamics, conventional gas exchange, and the VA/Q distribution by the multiple inert gas elimination technique (MIGT) were measured before (baseline), during (ALM 15), at the end of (ALM 30), and at 30-min intervals after (POSTALM 30, 60, and 90) the intravenous infusion of 0.5 mg/kg body weight of almitrine over 30 min. Almitrine significantly increased PaO2 from 78 +/- 15 mm Hg to 140 +/- 49 at ALM 15 and 138 +/- 52 at ALM 30. AaPO2 and QS/QT decreased during the administration of the drug. The MIGT showed that almitrine redistributed pulmonary blood flow from shunt areas (reduction from 29 +/- 11 to 17 +/- 11% of QT) to lung units with normal VA/Q ratios (increase from 63 +/- 9 to 73 +/- 6% of QT). The Ppa increased from 26 +/- 5 to 30 +/- 5 mm Hg without changes in QT. Changes were transient, returning toward baseline 30 min after stopping the infusion of the drug. Almitrine significantly reduced the VA/Q inequalities present in ARDS and may be useful in the management of those patients.     

Mechanisms of gas-exchange impairment in idiopathic pulmonary fibrosis

To investigate the mechanisms of pulmonary gas-exchange impairment in idiopathic pulmonary fibrosis (IPF) and to evaluate their potential relationship to the CO diffusing capacity (DLCO), we studied 15 patients with IPF (mean DLCO, 52% of predicted) at rest (breathing room air and pure O2) and during exercise. We measured pulmonary hemodynamics and respiratory gas-exchange variables, and we separated the ventilation-perfusion (VAQ) mismatching and O2 diffusion limitation components of arterial hypoxemia using the multiple inert gas elimination technique. At rest VA/Q mismatching was moderate (2 to 4% of cardiac output perfusing poorly or unventilated lung units), and 19% of AaPO2 was due to O2 diffusion limitation. During exercise VA/Q mismatch did not worsen but the diffusion component of arterial hypoxemia increased markedly (40% AaPO2, p less than 0.005). We observed that those patients with higher pulmonary vascular tone (more release of hypoxic pulmonary vasoconstriction) showed less pulmonary hypertension during exercise (p less than 0.05), less VA/Q mismatching [at rest (p less than 0.005) and during exercise (p less than 0.0025)], and higher arterial PO2 during exercise (p = 0.01). We also found that DLCO corrected for alveolar volume (KCO) correlated with the mechanisms of hypoxemia during exercise [VA/Q mismatching (p less than 0.025) and O2 diffusion limitation (p less than 0.05)] and with the increase in pulmonary vascular resistance elicited by exercise (p less than 0.005). In conclusion, we showed that the abnormalities of the pulmonary vasculature are key to modulate gas exchange in IPF, especially during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gas exchange mechanism of orthodeoxia in hepatopulmonary syndrome

The mechanism of orthodeoxia (OD), or decreased partial pressure of arterial oxygen (PaO2) from supine to upright, a characteristic feature of hepatopulmonary syndrome (HPS), has never been comprehensively elucidated. We therefore investigated the intrapulmonary (shunt and ventilation-perfusion [VA/Q] mismatching) and extrapulmonary factors governing PaO2 in 20 patients with mild to severe HPS (14 males, 6 females; 50 +/- 3 years old SE) at upright and supine, in random order. We set out a cutoff value for OD, namely a PaO2 decrease > or = 5% or > or = 4 mm Hg (area under the receiver operating characteristic curve, 0.96 each). Compared to supine, 5 patients showed OD (PaO2 change, -11% +/- 2%, -7 +/- 1 mm Hg, P < .05) with further VA/Q worsening (shunt + low VA/Q mode increased from 19% +/- 7% to 21% +/- 7% of cardiac output [QT], P < .05), as opposed to 15 patients who did not (+2% +/- 2%, +1+/- 1 mm Hg) with VA/Q improvement (from 20% +/- 4% to 16% +/- 4% of QT, P < .01). Cardiac output was significantly lower in OD patients in both positions. Changes in extrapulmonary factors at upright, such as increased minute ventilation and decreased QT, were of similar magnitude in both subsets of patients. In conclusion, our data suggest that gas exchange response to OD in HPS points to a more altered pulmonary vascular tone inducing heterogeneous blood flow redistribution to lung zones with prominent intrapulmonary vascular dilatations.     

Distributions of VA/Q in dog lungs obtained with the 50 compartment and the log normal approach.

From the lung wash-out ratios of six inert gases that were intravenously administered to 26 anaesthetized normal dogs, 120 distributions of ventilation--perfusion ratios (VA/Q) were determined, using two different techniques: the 50 compartment approach developed by Wagner et al. (1974a) and a least squares curve fitting method, comparing observed and calculated inert gas data corresponding to a single log normal distribution. The latter is defined by three parameters, the (geometric) mean VA/Q, the standard deviation of log VA/Q and a shunt fraction. A unimodal log normal fit was almost always obtained, but in 14 cases the 50 compartment approach yielded a bimodal distribution, which gave a better fit to the data in 7 cases. In most other cases the log normal distribution fitted better; the mean VA/Q's were about equal, but the standard deviations obtained from the log normal fit were often much less. It appears that, whereas in the log normal approach distributions of any sharpness can be fitted, the computer technique used in the 50 compartment approach, involving a smoothing algorithm, shortens and broadens any sharp and narrow peak in them. The effect of different smoothing factors in the 50 compartment approach was investigated. The PaO2 predicted from either distribution was about the same and somewhat less than the actual PaO2, so that one model is not superior to the other in describing oxygen transfer in the lung.     

Pulmonary gas exchange in severe chronic asthma. Response to 100% oxygen and salbutamol

Ventilation-perfusion (VA/Q) inequality has been evaluated using the multiple inert gas technique in nine nonsmoking patients (mean +/- SD, age 56 +/- 10 yr) with stable, severe, chronic asthma (partially reversible airway obstruction; baseline FEV1, 39 +/- 10% predicted) before and during 100% O2 breathing and then 15 min after three puffs (300 micrograms) of inhaled salbutamol. The aim of this study was to investigate whether this type of asthma was associated with a different pattern of VA/Q inequality from that observed in acute episodes and in particular to determine whether the VA/Q pattern was fixed or could be altered by bronchodilator agents or O2 breathing. The predominant pattern of VA/Q distribution was broad and unimodal but without shunt (VA/Q = 0) or low VA/Q areas (VA/Q less than 0.1 to greater than 0.005). The amount of VA/Q inequality as assessed by the dispersion of the distribution of pulmonary bloodflow (log SDQ) was not great (log SDQ, 0.77 +/- 0.09), and no correlation was found with the degree of airway obstruction, PaO2 or AaPO2. During 100% O2 breathing, VA/Q inequality worsened (from log SDQ of 0.77 +/- 0.09 to 1.11 +/- 0.21, p = 0.01) with an increase in the perfusion of low VA/Q units (from 0.43 +/- 0.66% to 6.3 +/- 6.5%, p = 0.02) but still no development of shunt. This suggests the presence of hypoxic pulmonary vasoconstriction breathing air, possibly contributing to the preservation of VA/Q relationships.(ABSTRACT TRUNCATED AT 250 WORDS)     

DLCO/Q and diffusion limitation at rest and on exercise in patients with interstitial fibrosis

Pulmonary diffusing capacity for carbon monoxide (DLCO) and pulmonary capillary blood flow (Qp) were measured on exercise in patients with a low DLCO with the aim of predicting, from the overall DL/Qp ratio, diffusion limitation for oxygen and relating it to the fall in arterial oxygen saturation actually observed. Five patients with cryptogenic fibrosing alveolitis (DLCO ranging from 20-54% predicted normal) exercised for 5 min at a work load equal to 60% of their maximum (45 to 90 watts). At 5 min (and previously at rest) they rebreathed rapidly for 15 sec from a 1.0 L bag containing helium (He), sulphur hexafluoride (SF6) and freon-22, 30% oxygen in argon and less than 1 ppm 11C-labelled carbon monoxide. Pulmonary capillary blood flow (Qp) and diffusing capacity (DLCO) were measured from flow-weighted breath-by-breath concentrations of freon-22 and 11CO, after correction for gas mixing delays (using He and SF6). Oxygen saturation (SaO2) (ear oximetry), MO2 and MCO2 and cardiac frequency were measured. PAO2 (ideal) was derived and mixed venous O2 saturation and content were calculated (Fick); PaO2 and PVO2 were derived from standard dissociation curves. For comparison, DLCO and Qp were measured in a similar fashion in five normal subjects exercising at 60 watts. Mean DLCO in patients with fibrosis was 9.62 (SD 2.88) ml.min-1, mm Hg-1 on exercise and mean Qp was 10.48 (SD 1.79) L.min-1 giving mean DLCO/Q ratios of 0.92 (SD 0.28). At 60 watts mean DLCO/Qp in normal subjects was 2.54 (SD 0.3), 2.76-times greater than in patients. SaO2% fell in patients by 3-15% on exercise. Predictions of alveolar-end capillary PO2 gradients from these overall DL/Q gradients showed that diffusion limitation accounted for 99% of the alveolar-arterial PO2 gradient on exercise in fibrosing alveolitis. Hughes (1991 Respir. Physiol. 83:167-178) [corrected] suggests that this simple approach overestimates the contribution of diffusion limitation by about 30%.     

Chronic obstructive pulmonary disease and anaesthesia: formation of atelectasis and gas exchange impairment.

Gas exchange impairment and the development of atelectasis during enflurane anaesthesia were studied in 10 patients (mean age 70 yrs) with chronic obstructive pulmonary disease (COPD). Awake, no patient displayed atelectasis as assessed by computed X-ray tomography. The ventilation/perfusion distribution (VA/Q), studied by the multiple inert gas elimination technique, displayed an increased dispersion of VA/Q ratios (the logarithmic standard deviation of the perfusion distribution, mean log Q SD 0.99; upper 95% confidence limit of normal subject: 0.60), and increased perfusion of regions with low VA/Q ratios (0.005 less than VA/Q less than 0.1: 5.4% of cardiac output). Shunt was negligible (mean 0.6%). Computed chest tomography showed significantly larger cross-sectional thoracic areas than previously seen in subjects with healthy lungs (p less than 0.01). No atelectasis was seen in any patient. During anaesthesia there was a further worsening of the VA/Q mismatch with significantly increased log Q SD (1.29, p less than 0.05) but no increase in shunt (mean 1%). Minor atelectatic areas were noted in three patients, the others displayed no atelectasis at all. Chest dimensions were reduced by no more than 3% during anaesthesia, suggesting an unchanged or only minimally affected functional residual capacity. These findings contrast with those seen in patients with healthy lungs in whom atelectasis and shunt regularly develop during anaesthesia.     

Mechanical ventilation with 100% oxygen does not increase intrapulmonary shunt in patients with severe bacterial pneumonia

Pure oxygen ventilation has been shown to increase the right to left shunt QS/QT in both normal and diseased lungs. Nitrogen absorption atelectasis, an explanation of the phenomenon, is likely to occur in lung units with low ventilation/perfusion ratio. In 11 patients with severe unilateral or bilateral bacterial pneumonia, we assessed the effects of increasing FlO2 from maintenance level (m = 0.44 +/- 0.11) to 1.0. Venous admixture (QVA/QT) was calculated using the O2 method, and the distribution of the VA/Q ratios were assessed with the 6 inert gas (IG) technique providing the distribution between the true shunt (QS/QT IG) and the low VA/Q units. Although a large part of perfusion was distributed preferentially to low VA/Q units, ranging from 2 to 43% of cardiac output, thus placing large zones of lung parenchyma at risk of absorption atelectasis, QVA/QT decreased from 31 +/- 13% to 25 +/- 10% and IG shunt did not increase after 30 min of O2 ventilation. In addition, QS/QT IG remained unaltered despite PVO2 increased from 32 to 43 mmHg, suggesting a poor level of hypoxic vasoconstriction in human bacterial pneumonia.     

Hypoxemia in acute pulmonary embolism

Most patients with severe, acute pulmonary embolism (PE) have arterial hypoxemia. To further define the respective roles of ventilation to perfusion (VA/Q) mismatch and intrapulmonary shunt in the mechanism of hypoxemia, we used both right heart catheterization and the six inert gas elimination technique in seven patients with severe, acute PE (mean vascular obstruction, 55 percent) and hypoxemia (mean PaO2, 67 +/- 11 mm Hg). None had previous cardiopulmonary disease, and all were studied within the first ten days of initial symptoms. Increased calculated venous admixture (mean QVA/QT 16.6 +/- 5.1 percent) was present in all patients. The relative contributions of VA/Q mismatching and shunt to this venous admixture varied, however, according to pulmonary radiographic abnormalities and the time elapsed from initial symptoms to the gas exchange study. Although all patients had some degree of VA/Q mismatch, the two patients studied early (ie, less than 48 hours following acute PE) had normal chest x-ray film findings and no significant shunt; VA/Q mismatching accounted for most of the hypoxemia. In the others a shunt (3 to 17 percent of cardiac output) was recorded along with radiographic evidence of atelectasis or infiltrates and accounted for most of the venous admixture in one. In all patients, a low mixed venous oxygen tension (27 +/- 5 mm Hg) additionally contributed to the hypoxemia. Our findings suggest that the initial hypoxemia of acute PE is caused by an altered distribution of ventilation to perfusion. Intrapulmonary shunting contributes significantly to hypoxemia only when atelectasis or another cause of lung volume loss develops.