Pulmonary Extravascular Water Volume Research Articles

Failure of positive end-expiratory pressure to decrease lung water content in alloxan-induced pulmonary edema.

The effect of 10 cm H2O of positive end-expiratory pressure (PEEP) on pulmonary extravascular water volume (PEWV) was measured in an animal model of noncardiogenic pulmonary edema. Three groups of animals were studied: (1) controls, (2) those given a saline infusion plus alloxan, and (3) those which received saline infusion plus alloxan and PEEP. All animals were ventilated with a constant volume ventilator. Mean PEWV (+/- SEM) in milliliters per gram of dry lung weight was 4.00 +/- 0.21 for group 1, 6.01 +/- 0.70 for group 2, and 5.77 +/- 0.83 for group 3. Mean PEWV increased significantly in both alloxan groups (groups 2 and 3) as compared to the control group (for both, p less than 0.05); however, PEWV did not differ significantly in the group that received PEEP, as compared to the group ventilated without PEEP. Arterial PO2 and airway pressure required to deliver a constant tidal volume did not change significantly in the experimental groups as compared to the control group. It was concluded that PEEP does not decrease lung water content in pulmonary edema caused by damage to fluid-exchanging vessels.

Protective effects of ONO-5046·Na, a specific neutrophil elastase inhibitor, on postperfusion lung injury

Background. Polymorphonuclear neutrophil elastase might contribute to postperfusion lung injury, so we evaluated the protective effect of ONO-5046·Na, a specific inhibitor of polymorphonuclear neutrophil elastase, against such an injury.Methods. The study was done using 8 mongrel dogs that received ONO-5046·Na (15 mg/kg per hour) (group O) and 8 control dogs (group C), all of which had 1 hour of partial bypass and 5 hours of observation.Results. The respiratory index showed no significant changes in group O, but increased significant in group C (1.4 ± 2.0 versus 5.1 ± 4.7, p = 0.0047). Pulmonary extravascular water volume increased markedly in group C but only slightly in group O (group C 20.6 ± 8.7, group O 11.2 ± 2.7 mL/kg; p = 0.0005). Blood concentrations of polymorphonuclear neutrophil elastase and interleukin-6 showed more than a tenfold increase in group C (PMN elastase, group C 12.9 ± 12.8, group O 2.4 ± 1.3 ng/mL; IL-b, group C 11.0 ± 9.3, group O 2.9 ± 3.8 pg/mL; p < 0.05) but were only slightly higher in group O. Histologic examination revealed interstitial and intraalveolar edema in group C, but group O was virtually normal.Conclusions. ONO-5046·Na inhibits polymorphonuclear neutrophil elastase and maintains better pulmonary function, so it should reduce postperfusion lung injury.

Measurement of extravascular lung water by the double indicator dilution method using heat and sodium in horses under general anesthesia.

Rapid infusion is believed to be harmful to the lung, however, the pathological status of pulmonary edema resulting from excessive fluid therapy in horses has not been clarified because the quantitative diagnosis of pulmonary edema is impossible. To evaluate the precision of the double indicator dilution method using heat and sodium in horses, which allows the quantitative diagnosis of pulmonary edema, we compared extravascular lung water volume measured using a lung water computer based on the theory of the double indicator dilution method with that determined by the direct method. The value of extravascular thermal volume (ETV) determined by the double indicator dilution method was 7.82 +/- 0.62 ml/kg and the detection ratio of ETV to the value of pulmonary extravascular water volume (PEWV) by the direct method was 0.996 +/- 0.038. There was a significant correlation between ETV and PEWV (P < 0.05), and the regression line was Y = 1.23 X - 1.73 with a correlation coefficient of 0.953. The value of extravascular lung water determined by the double indicator dilution method was significantly consistent with that obtained by the direct method, indicating the high precision of the double indicator dilution method in normal horse lungs.

Commercial double-indicator-dilution densitometer using heavy water: Evaluation in oleic-acid pulmonary edema

We evaluated a commercially available, double-indicator-dilution densitometric system for the estimation of pulmonary extravascular water volume in oleic acid-induced pulmonary edema. Indocyanine green and heavy water were used as the nondiffusible and diffusible tracers, respectively. Pulmonary extravascular water volume, measured with this system, was 67% of the gravimetric value (r = 0.91), which was consistent with values obtained from the radioisotope methods. The measured volume was not influenced by changes in cardiac index over a range of 1 to 4 L.min.m2. This system is less invasive than the thermal-dye technique and has potential for repeated clinical measurements of pulmonary extravascular lung water and cardiac output.

Impaired pulmonary and cardiac function after maximal exercise.

The cardiopulmonary response to maximal rowing exercise of short duration was studied in six healthy well-trained oarsmen. The lung diffusing capacity for carbon monoxide was significantly decreased below the pre-exercise value for 2.5 days post-exercise (P less than 0.05). Residual volume (RV) showed a significantly increased value at 30 min of recovery (P less than 0.01) with no change in total lung capacity. There was no significant change in transthoracic electrical impedance following exercise but a decrease may have been masked by the increased RV. The changes in the pulmonary parameters may reflect the occurrence of a transient interstitial lung oedema. Exercise-induced bronchoconstriction may be a part of the cardiopulmonary response as peak expiratory flow rate (PEFR) was significantly reduced at 30 min of recovery. The reason for the increase in pulmonary extravascular water volume may be a marked distension of the lung capillaries due to increased blood volume in the lungs and as a consequence increased vascular permeability. The changes may also be caused by impaired myocardial contractility indicated by a split impedance dZ/dt waveform, not previously described in healthy persons, which occurred in all six subjects immediately following exercise.

The effects of unilateral pulmonary artery occlusion on pulmonary extravascular water volume and broncho-alveolar lavage under unilateral pulmonary artery occlusion

The effects of unilateral pulmonary artery occlusion on pulmonary extravascular water volume and broncho-alveolar lavage under unilateral pulmonary artery occlusion

Exponential increases in pulmonary intravascular and extravascular fluid volumes by overperfusion with dextran 70 in anesthetized dogs.

In the lung overperfused by dextran 70, it is not known how intravascular blood volume and extravascular water volume increase as a function of pulmonary microvascular pressure. To determine their characteristics, we produced an overperfusion state (high pressure and high blood flow) by infusing dextran 70 (100 ml/kg over 30 min) into 15 anesthetized dogs. Using the thermal and dye dilution technique, we simultaneously estimated the pulmonary blood volume (PBV) and the extravascular lung thermal volume (EVLTV), and correlated mathematically these variables with pulmonary artery end-diastolic pressure (PAEDP). Here, we defined PAEDP as the pulmonary microvascular pressure. From the values determined before, during and after dextran 70 infusion, we obtained the following exponential relations. PBV(ml/kg) = 30[1-0.902(e-0.021PAEDP(mmHg)) EVLTV(ml/kg) = 5.15(e0.027PAEDP (mmHg)) From these mathematical relations, we conclude that: (1) the pulmonary blood volume increases rapidly at low pressure and slowly at high pressure; and (2) the pulmonary extravascular water volume increases slowly at low pressure and then increases rapidly at high pressure. In addition, this equation indicates that the critical pressure from which the pulmonary extravascular water volume exceeds the upper limit of its normal volume is about 17 mmHg in PAEDP. Infusion of dextran 70 increased plasma macromolecular osmotic pressure from 20.8 +/- 0.6 (mean +/- SD) mmHg before infusion to 43.7 +/- 1.4 mmHg after infusion. Therefore, dextran 70 does not change the critical microvascular pressure against pulmonary edema.

FLUID VOLUME BALANCE BETWEEN PULMONARY INTRAVASCULAR SPACE AND EXTRAVASCULAR SPACE IN DOGS

We aimed to study the agreement of estimates of the pulmonary blood volume by the double indicator dilution method and the direct destructive method and the fluid volume balance between the pulmonary intravascular and extravascular spaces. We employed the double indicator dilution method using heat and indocyanine green, with a single injection (into the right atrium) and double sampling technique, that is from the pulmonary artery trunk (PAT) and the aortic root (Ao). With this method, we simultaneously determined the pulmonary extravascular water volume (PEWV), defined as the extravascular lung thermal volume estimated in Ao (LTVAo), and the pulmonary blood volume (PBV) from PAT to the left atrium (LA) (PBVPAT-LA). Dogs were divided into groups: a group without intervention (n = 16), a group loaded with dextran (n = 12) and a group loaded with alloxan (n = 7). When all groups were included, PBVPAT-LA (ml/kg) = 1.02 X PBVdirect(g/kg) + 0.96, n = 35, r = 0.83 where PBVdirect means the blood contents from the pulmonary artery bifurcation to the pulmonary vein measured by the direct destructive method. We substantiated the validity of the use of the double indicator dilution method. In studying the fluid volume balance, based on the results of the direct destructive method, the pulmonary intravascular-extravascular fluid volume ratio (intra/extra) was 1.3 +/- 0.3 (mean +/- SD) in the control state, implying that the interstitium in the lung is relatively "dry". As overt pulmonary edema developed by dextran infusion, the ratio exponentially decreased to 1.0 +/- 0.1 (p less than 0.01). The behavior of the fluid volume balance in question (intra/extra), studied with the double indicator dilution method, was essentially similar to that analyzed by the direct destructive method.

Pulmonary blood volume and pulmonary extravascular water volume in men.

In order to estimate the pulmonary blood volume between the pulmonary artery trunk and the left atrium (PBV PAT-LA), simultaneously with the pulmonary extravascular water volume (PEWV) in the chronically stable cardiac patients, we employed the double indicator dilution method using heat as a diffusible indicator and indocyanine green as a non-diffusible indicator. The PEWV was obtained as the extravascular lung thermal volume estimated in the aortic root (LTVAo). In the group of hemodynamically normal patients, in spite of ischemic heart disease (G-N, n = 22), the mean pulmonary artery wedge (PAW) pressure was 9.3 +/- 3.9 mmHg (mean +/- SD), PBVPAT-LA was 8.95 +/- 1.71 ml/kg, LTVAo was 5.71 +/- 1.37 ml/kg and PBVPAT-LA/LTVAo ratio was 1.64 +/- 0.44. In the group of hemodynamically slightly compromised patients with mitral stenosis (G-MS, n = 13), the mean PAW pressure was 14.2 +/- 2.6 mmHg, PBVPAT-LA was 11.12 +/- 2.86 ml/kg, LTVAo was 5.68 +/- 1.41 ml/kg and PBVPAT-LA/LTVAo ratio was 2.02 +/- 0.58. Between the two groups, LTVAo was not statistically significant, whereas the mean PAW pressure, PBVPAT-LA and PBVPAT-LA/LTVAo ratio were all significantly increased in G-MS (p less than 0.05). Neither PBVPAT-LA nor LTVAo correlated with the mean PAW pressure in both groups. From PBVPAT-LA/LTVAo ratio, fluid volume in the intravascular space was greater than that in the extravascular space in both groups. From LTVAo, PEWV in G-MS was identical with that in G-N, in spite of the elevated mean PAW pressure. Therefore, even in the patients with mitral stenosis, the interstitium in the lung is kept "dry" under conditions of the mean PAW pressure below 20 mmHg. The safety factors that prevent pulmonary edema, as evidenced in animal studies, seem to operate effectively in man.

A problem intrinsic to the measurements of the pulmonary extravascular water volume by the thermal-dye technic with the sampling site in the bifurcation of the aorta. Thermal equilibrium with the aortic wall.

When estimating the pulmonary extravascular water volume (PEWV) as the lung thermal volume (LTV), by the double indicator dilution technic using heat and indocyanine green (ICG), a part of the left ventricular wall comes to the thermal equilibrium, and this leads to an overestimation of PEWV, when the samplings are made in the aortic root. In a previous study from this laboratory, this overestimation was approximately 10% of the measured LTV in the aortic root. In the present study, we evaluated the extent to which the thermal equilibrium with the aortic wall would cause LTV to slightly overestimate PEWV. For this purpose, we injected a mixture of the indicators into the right atrium, and recorded the indicator dilution curves at the bifurcation of the aorta (AB). We then compared this LTV with the one calculated from the indicator dilution curves recorded simultaneously in the aortic root (Ao). We obtained the following results: Firstly, the values of cardiac output (CO) from the dye dilution curve and from the thermodilution curve at two sites, Ao and AB, were all in agreement. Secondly, LTV estimated in Ao (LTVAo) and LTV estimated in AB (LTVAB) were not the same, and their relationships were: LTVAB = 1.21 X LTVAo + 0.44 (ml/kg), n = 32, (r = 0.98, p less than 0.001) A close agreement of CO determined at two sites indicated that there was virtually no loss of heat between the two sampling sites, Ao and AB. An excess of LTVAB over LTVAo came to about 20%, and this excess appeared to be ascribable to the incorporation of the thermally equilibrated "volume" of the aortic wall. This finding appeared to be a challenge to the validity of estimating LTV when sampling the indicators in the distal abdominal aorta.

Pulmonary extravascular water volume in heart diseases: the effect of isosorbide dinitrate on hemodynamic pulmonary edema

二重指示薬希釈法により肺血管外水分量を心疾患32例,すなわち冠動脈疾患20例,僧帽弁疾患11例,拡張型心筋症1例において測定した.さらに肺血管外水分量に対する硝酸薬の影響も検討した.肺血管外水分量は熱とICG平均循環時間の差と,心拍出量の積により求めた.肺うつ血群の肺血管外水分量は12.6±3.3ml/kgと正常肺血行動態群6.6±2.2ml/kgに比し大であつた(p<0.001).肺血管外水分量は肺動脈楔入圧および肺動脈平均圧と良い相関を示した(p<0.001).硝酸薬舌下後,肺うつ血群では肺動脈平均圧の約10mmHgの低下とともに肺血管外水分量も11.1±2.3から9.1±2.5ml/kgへ減少したが(p<0.01),正常肺血行動態群では変わらなかつた.

High surface tension pulmonary edema induced by detergent aerosol.

The effect of the detergent dioctyl sodium sulfosuccinate on pulmonary extravascular water volume (PEWV) was studied in adult anesthetized mongrel dogs. The detergent was dissolved as a 1% solution in a vehicle of equal volumes of 95% ethanol and normal saline and administered by ultrasonic nebulizer attached to the inspiratory tubing of a piston ventilator. Two hours following detergent aerosol PEWV measured gravimetrically was increased compared with either animals receiving no aerosol or those receiving an aerosol of vehicle alone. Loss of surfactant activity and increased alveolar surface tension were demonstrated by Wilhelmy balance studies of minced lung extracts, by a fall in static compliance, and by evidence of atelectasis and instability noted by gross observation and by in vivo microscopy. No significant changes in colloid oncotic pressure or pulmonary microvascular hydrostatic pressure were observed. These data suggest that pulmonary edema can be induced by increased alveolar surface tension and support the concept that one of the major roles of pulmonary surfactant is to prevent pulmonary edema.

Effect of acute hypoxia on airway and vascular exchangeable lung water spaces in dogs.

To determine if alveolar hypoxia causes subclinical noncardiogenic pulmonary edema, we measured in 8 dogs the rebreathing pulmonary tissue volume (Vt) and the pulmonary extravascular water volume using the single-pass double-indicator dilution method. After baseline measurements, the dogs were ventilated with the lowest concentration of oxygen that would not cause left ventricular failure (9 to 13% O2). One to 6 h of hypoxia had no effect on Vt, but caused a reversible 38% fall in pulmonary extravascular lung water volume by the indicator method (p less than 0.01). The ratio of the extravascular to vascular volumes estimated from the relative peak heights of the 2 indicator dilution curves did not change with hypoxia, which implies that hypoxia caused a derecruitment of pulmonary blood vessels rather than a real decrease in extra-vascular lung water volume. This conclusion is supported by our rebreathing measurement of the airway exchangeable tissue volume, which is virtually independent of tissue perfusion, and which did not fall during hypoxia. To determine if this alteration in the pulmonary circulation can cause pulmonary edema when the cardiac output is increased, we opened a femoral artery to femoral vein shunt in 9 additional dogs during ventilation with 9 to 13% oxygen. Cardiac output increased over 50% but pulmonary edema developed in only 1 dog, the dog that also had the highest mean pulmonary artery pressure of the group (35 mmHg versus group mean of 26 mmHg during hypoxia). We conclude that 1 to 6 h of alveolar hypoxia in dogs consistently decreases the volume of perfused lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

A problem in the measurements of pulmonary extravascular water volume by double indicator dilution method, using heat and dye Thermal diffusion into the left ventricular wall.

Pulmonary extravascular water volume was obtained as the lung thermal volume (LTV) in mongrel dogs (n = 31) by double indicator dilution method, using negative heat and indocyanine green. We used a technic of one injection site (right atrium) and two sampling sites, i.e., pulmonary artery trunk and aortic root. In 13 dogs, cardiac outputs determined simultaneously from thermodilution curves in pulmonary artery trunk, aortic root and from dye dilution curve in aortic root, were in a good agreement with a coefficient of variation of +/- 12%. Lung thermal volume measured twice within a period of 5 minutes in 17 dogs, gave closely similar values with a coefficient of variation of +/- 9%. Lung thermal volume was 5.7 +/- 1.1 ml/kg (mean +/- SD) and corresponding "weighed lung water" (WLW), which was measured by destructive, direct method, was 5.0 +/- 1.0 ml/kg, the ratio of LTV to WLW (LTV/WLW) being 1.2 +/- 0.2 in control state. LTV/WLW ratio was 1.2 +/- 0.2 in 11 dogs loaded with dextran, and 1.1 +/- 0.1 in 6 dogs loaded with alloxan. Thus the lung thermal volume slightly exceeded WLW. In order to evaluate the extent to which the thermal diffusion into the left ventricular wall would cause LTV to slightly overestimate the pulmonary extravascular water volume, dye dilution curves and thermodilution curves were recorded simultaneously in the left atrium (LA) and aortic root (Ao) in a total of 25 runs in 5 dogs. The ratio of LTV obtained in LA to that in Ao was 0.9 +/- 0.1 (mean +/- SD). It was concluded that the pulmonary extravascular water volume was overestimated, by about 10% due to the thermal diffusion into the left ventricular wall.

Effect of Positive End-Expiratory Pressure on Lung Water in Pulmonary Edema Caused by Increased Membrane Permeability

Pulmonary edema caused by increased membrane permeability was created in dogs by alloxan and infusion of saline solution. Pulmonary extravascular water volume was measured gravimetrically using the supernatant hemoglobin concentration to estimate red cell mass in the calculation of residual pulmonary blood volume. Three groups were studied for two hours: a control group, a group given alloxan and mechanical ventilation without positive end-expiratory pressure (PEEP), and a group given alloxan and mechanical ventilation with 10 cm H 2O of PEEP. After two hours, alloxan caused moderately severe pulmonary edema in the two experimental groups, but PEEP had no effect on the accumulation of pulmonary extravascular water volume. No sustained differences in pulmonary or systemic hemodynamics were present throughout two hours of pulmonary edema. The pulmonary shunt was increased in the group without PEEP but was similar in the control group and the group with PEEP. No significant changes in alveolar dead space were noted among the three groups.

High surface tension pulmonary edema

Dogs were anesthetized with pentobarbital and placed on a piston ventilator with room air. Ten animals received an endobronchial lavage of normal saline (3 mg/kg). Ten other animals received an endobronchial lavage of the same volume of a nonionic detergent, Tween 20, 5% in saline. Detergent lavage was shown by Wilhelmy balance to increase surface tension of lung extracts. Saline lavage did not alter the surface tension of lung extracts. No significant differences between the groups were noted in cardiac output, left ventricular end diastolic pressure, mean pulmonary artery pressure, or colloid oncotic pressure. Static compliance and arterial PO 2 were decreased following detergent lavage. Animals were sacrificed 2 hr after lavage and pulmonary extravascular water volume (PEWV) was measured gravimetrically. Saline-lavaged lungs with normal surface tension had a PEWV of 4.3 ml/g dry lung. Tween-lavaged lungs with increased surface tension had a PEWV of 5.3 ml/g dry lung ( P < 0.005). When the estimated volume of residual lavage solution remaining in the lung parenchyma was subtracted from the total wet lung wt, the corrected PEWV was 3.62 ± 0.12 ml/g dry lung for saline-lavaged lung and 4.76 ± 0.19 ml/g dry lung for Tween-lavaged lung. PEWV for 11 control animals ventilated 2 hr without lavage was 3.61 ± 0.13 ml/g dry lung. It is concluded that, experimentally, high alveolar surface tension can induce pulmonary edema even when pulmonary microvascular hydrostatic and colloid oncotic pressures are normal.

Effect of different levels of positive end-expiratory pressure on lung water content.

To compare the effects of 2-, 5-, and 10-cmH2O positive end-expiratory pressure (PEEP) on pulmonary extravascular water volume (PEWV), pulmonary blood volume (PBV), pulmonary dry weight (PDW), and distensibility, we separately ventilated perfused dogs' lungs in situ and produced pulmonary edema with oleic acid (0.06 ml/kg). Three groups were studied: I, PEEP, 5 cmH2O in both lung; II, PEEP, 2 cmH2O in one lung and 10 cmH2O in the other; and III, PEEP, same as II, but the chest was rotated to compensate for differences in heights. The PEWV and distensibility were less (P less than 0.05) in lungs exposed to 10-cmH2O than to either 2- or 5-cmH2O PEEP. After chest rotation, the difference between 10- and 2-cmH2O PEEP on PEWV was eliminated but that on distensibility was not. We conclude that 10-cmH2O PEEP 1) decreased water content because of lung volume-induced effects on intravascular hydrostatic pressure and 2) improved distensibility by recruitment of alveoli, irrespective of PEWV.

Non-hydrostatic pulmonary edema after coronary artery ligation in dogs. Protective effect of indomethacin.

Pulmonary edema which develops during acute myocardial infarction is generally believed to result solely from pulmonary microvascular hypertension. However, patient with myocardial infarction and pulmonary edema occasionally are found to have normal pulmonary wedge pressure. We report data indicating that pulmonary edema develops after coronary artery ligation despite stable microvascular pressure. Four groups of open-chest dogs were studied: (1) nine dogs with left anterior descending coronary artery ligation, (2) seven dogs with sham coronary ligation, (3) seven dogs ligated after beginning an infusion of indomethacin (5 mg/kg per hr), and (4) five dogs ligated after an infusion of the drug's vehicle was begun. Extravascular lung water and pulmonary blood volume were measured at hourly intervals during the 2 hours before and after coronary ligation or sham ligation. Gravimetric lung water was measured immediately thereafter. Changes of net pulmonary intravascular driving force (the difference of microvascular hydrostatic and oncotic pressure) after ligation or sham ligation were small and comparable in all groups. Pulmonary blood volume did not change in any group. Pulmonary extravascular water volume remained constant in the sham group but rose significantly in the ligated group. Gravimetric lung water also was significantly higher in the latter group. We interpret these results to indicate that factors other than microvascular pressure can mediate the formation of these results to indicated that factors other than microvascular pressure can mediate the formation of edema during acute myocardial infarction; increased pulmonary microvascular permeability may be responsible. Indomethacin infusion blocked the formation of edema after coronary ligation, even though net microvascular driving force was highest in this group. Infusion of the vehicle alone did not prevent edema. The mechanism by which indomethacin exerts this protective effect is unclear but is probably a result of its inhibition of cyclo-oxygenase or cyclic nucleotide phosphodiesterase.

Experimental Evaluation of Reexpansion Pulmonary Edema

Reexpansion pulmonary edema following pneumothorax is clinically uncommon but occasionally life threatening. This study documents the functional and anatomical abnormalities that occur when a collapsed lung is reexpanded. Right pneumothorax was created through open tube thoracostomy in 30 goats. The animals were divided into six groups by duration of pneumothorax (24, 48, or 72 hours) and technique of reexpansion (waterseal vs 10 cm H 2O suction). Arterial blood gases and alveolar-arterial oxygen tension difference ( a-aD o 2) were analyzed before pneumothorax and after reexpansion. Each lung was reexpanded for 2 hours, chest roentgenograms were obtained, and both lungs were removed. The left lung served as the control. Both lungs were checked for surfactant activity and pulmonary extravascular water volume (PEWV). Light and electron microscopy were also performed. Anatomical and functional changes were present in the reexpanded lung after relief of pneumothorax. Both increased time of collapse and suction reexpansion tended to correlate with increased PEWV, decreased surfactant and arterial P o 2, and increased a-aD o 2.

Incidence and pathophysiology of pulmonary edema in fulminant hepatic failure

Thirty-seven of 100 consecutive patients with fulminant hepatic failure had clinical and radiological evidence of pulmonary edema. None of them had clinical evidence of left heart failure, and the pulmonary artery wedge pressure measured in 12 patients was normal. Similarly, there was no evidence to incriminate renal failure, endotoxemia, or hypoalbuminemia. However, there was a significantly higher incidence of pulmonary edema in patients with cerebral edema, suggesting either a central origin for the pulmonary edema or common factors predisposing to edema in both sites. An additional local factor may have been the presence of intrapulmonary vasodilatation. Detailed isotope studies in 11 patients showed a significantly increased pulmonary extravascular water volume in the patients with pulmonary edema which was in keeping with the severity of the radiological changes. Although the over-all mortality was higher in those patients with pulmonary edema than in those without, the difference was not significant, and early ventilation with positive and expiratory pressure achieved adequate oxygenation in all but 3 patients.