The thermal-dye method of lung water measurement is reliable at a low cardiac output

The measurement of lung water by the thermal-dye double indicator dilution technique was evaluated in dogs with normal and edematous lungs during a state of reduced cardiac output. The technique used cold indocyanine green dye to measure extravascular thermal volume (EVTV) as an estimate of extravascular lung water (EVLW). Anesthesia was maintained with pentobarbital. In 15 of 21 animals, pulmonary edema was first induced with oleic acid (0.75 to 0.18 ml/kg). Cardiac output (CO) was then decreased by a combination of propranolol and slow exsanguination (mean CO reduction to 36% of baseline). Extravascular lung water produced in this model ranged from 1.4 to 30.2 ml/kg. Predetermination measurements of EVTV correlated closely with EVLW as determined by gravimetric analysis (EVTV = 1.1 EVLW + 4.7 ml/kg, n = 21, r = 0.93, P less than 0.001). Thermodilution cardiac output measured in the abdominal aorta (used in the calculation of the EVTV) correlated well with simultaneous measurements of cardiac output by both indocyanine green dye dilution and pulmonary artery thermodilution (r = 0.86 and r = 0.88, respectively, pretermination). The thermal-dye technique appears to provide an accurate reflection of lung water in normal and edematous lungs, even in the presence of a low cardiac output.     

Effects of negative extra-thoracic pressure ventilation on extravascular lung water volume and central blood volume in normal dogs

In negative extra-thoracic pressure ventilation (NETPV), lung water volume and central blood volume (CBV) could increase because of increased venous return and intensified negative interstitial pressure. The effects of NETPV on the extravascular lung water and CBV were examined in ten normal dogs by the double-indicator method using Na and cold water. The lung water volume measured by the method (EVTV) was compared with the lung water volume measured by the gravimetric method (EVLW) in 17 dogs. EVTV did not show any significant change in any ventilation modes compared with IPPV. CBV decreased from 21.9 ml.kg-1 to 19.2 ml.kg-1 in CPPV compared with IPPV (P less than 0.05). EVTV correlated well (r = 0.91, P less than 0.001) with EVLW. In normal dogs, NETPV did not change the lung water volume and CBV. NETPV dogs do not seem to have any disadvantage in respect of lung water volume compared with conventional positive pressure ventilations.     

Cardiovascular and blood gas responses to ketanserin in canine pulmonary edema induced by oleic acid

This study was performed to determine the cardiovascular and respiratory effects of ketanserin, a specific 5-HT2 antagonist, following oleic acid lung injury in anesthetized dogs. Following intravenous administration of oleic acid (0.1 ml/kg) to a control group (N = 7), systemic blood pressure decreased significantly. This lowered level of systemic blood pressure was maintained throughout the experiment. Cardiac output gradually decreased following oleic acid administration, while total peripheral resistance, pulmonary vascular resistance, and pulmonary arterial pressure were increased significantly. In a group treated with intravenous ketanserin (0.16 mg/kg, N = 7) 60 min after the injection of oleic acid, no decrease in cardiac output was seen. The increased total peripheral resistance, pulmonary vascular resistance, and pulmonary arterial pressure following injection of oleic acid also were returned toward preoleic acid levels. However systemic blood pressure showed no significant improvement after treatment with ketanserin nor did ketanserin protect against progressive hypoxemia following pulmonary injury with oleic acid. A progressive increase in hemoglobin concentration was seen after oleic acid in the control group. This recovered toward the preoleic acid level following treatment with ketanserin. The postmortem lung wet-dry weight ratio was significantly lower in the treated group compared with the control group. In conclusion, these data suggest that serotonin may have a role in including cardiopulmonary hemodynamic disturbances and in producing increases in extravascular lung water when pulmonary edema is induced by oleic acid injection in anesthetized dogs.     

Thermal dye double indicator dilution measurement of lung water in man: comparison with gravimetric measurements.

The thermal dye double indicator dilution technique for estimating lung water was compared with gravimetric analyses in nine human subjects who were organ donors. As observed in animal studies, the thermal dye measurement of extravascular thermal volume (EVTV) consistently overestimated gravimetric extravascular lung water (EVLW), the mean (SEM) difference being 3.43 (0.59) ml/kg. In eight of the nine subjects the EVTV -3.43 ml/kg would yield an estimate of EVLW that would be from 3.23 ml/kg under to 3.37 ml/kg over the actual value EVLW at the 95% confidence limits. Reproducibility, assessed with the standard error of the mean percentage, suggested that a 15% change in EVTV can be reliably detected with repeated measurements. One subject was excluded from analysis because the EVTV measurement grossly underestimated its actual EVLW. This error was associated with regional injury observed on gross examination of the lung. Experimental and clinical evidence suggest that the thermal dye measurement provides a reliable estimate of lung water in diffuse pulmonary oedema states.     

Mechanisms involved in acute lung edema induced in dogs by oleic acid

We investigated mechanisms related to the development of acute lung edema, as induced by oleic acid in adult mongrel dogs. The intravenous injection of oleic acid (0.04 ml/kg) was considered to induce a permeability edema, as an enhancement of transvascular protein clearance was observed after the injection. The effects of oleic acid injection on systemic blood pressure (SBP), pulmonary arterial pressure (PAP), pulmonary arterial wedge pressure (PAWP), cardiac output (CO) and airway pressure (AWP) were measured. A significant decrease in CO and increase in AWP were evident after the injection, but there were no changes in SBP, PAP and PAWP. Treatment of the animals with prostaglandin I2 (PGI2) did not alter the induction of edema by oleic acid. However, the decrease in CO and increase in AWP were normalized by treatment with PGI2. Blood platelet count was not affected by oleic acid given in a dose of 0.04 ml/kg. To determine the direct effect of oleic acid on the vascular endothelium, the agent was injected through a catheter placed in the pulmonary artery. Electron microscopic examination revealed severe vacuolation on the endothelium of the pulmonary artery after only 1 min of exposure to oleic acid. Increased permeation of Evans blue into the subendothelial tissue was also observed with oleic acid treatment, compared with findings in the controls. These results indicate that the lung edema induced by oleic acid is due to an increased protein clearance, probably through a direct toxic effect on the vascular endothelium rather than an indirect toxic effect of chemical mediators released from the aggregated platelets.     

Prevention of pulmonary edema developing in autoperfusing heart-lung preparation by leukocyte depletion

We investigated the preventive effect of leukocyte depletion on the development of pulmonary edema in a 12 h autoperfusing heart-lung preparation (AHLP). Sixteen mongrel dogs were divided into two groups: control group (group C, n = 9) and leukocyte depleted group (group L, n = 7). In group L, leukocytes were depleted with a leukocyte removal filter prior to the preservation. Extravascular thermal volume (EVTV) was measured by thermal-dye dilution technique as a parameter of pulmonary edema during preservation. The white blood cell (WBC) count was measured before and during preservation. After the procedure, extravascular lung water (EVLW) was measured by a gravimetric technique. In group C, the WBC count significantly decreased soon after the start of preservation, and subsequently remained without significant changes. In group L, the WBC count was maintained at a low level during the entire course of preservation. In group C, EVTV increased significantly with the preservation time. In group L, a significant increase in EVTV was only found at 12 h to a smaller extent than in group C. EVLW was significantly smaller in group L than in group C. In conclusion, the development of pulmonary edema was apparently prevented in the 12 h canine AHLP model by leukocyte depletion, and pulmonary leukocyte sequestration was considered as a cause of pulmonary edema in AHLP.     

The effect of nitroprusside on pulmonary edema, oxygen exchange, and blood flow in hydrochloric acid aspiration

In canine pulmonary capillary leak induced by intravenous oleic acid, reducing pulmonary wedge pressure (Ppw) reduces pulmonary edema, venous admixture (Qva/Qt), and cardiac output (Qt). The authors tested the possibility that in another canine model of pulmonary capillary leak, that induced by endobronchial instillation of hydrochloric acid, nitroprusside would reduce Ppw and edema without reducing Qt or oxygen delivery (QO2). In 18 dogs, the authors measured extravascular lung water (EVLW) by thermal-dye dilution and the hemodynamic and gas exchange variables before and at intervals (1, 1.5, 3, and 5 h) after .1 N HCl bronchial infusion. By 1 h, HCl increased EVLW from 175 to 250 ml and Qva/Qt from 11 to 21%. Immediately after the 1-h measurements, the dogs were divided into three equal groups: six controls (C) were maintained with a Ppw of 12 mmHg, while plasmapheresis (P) or nitroprusside (NP) reduced Ppw to 5 mmHg for the next 4 h. EVLW continued to increase to 548 ml in C, but did not increase further in P and NP. Weights of lungs excised at 5 h confirmed that P and NP reduced edema by 50% in 4 h. In C, Qva/Qt increased, but there was no reduction in Qt or QO2. In contrast, plasmapheresis reduced Qva/Qt, Qt, and QO2. With nitroprusside, Qt and QO2 were maintained despite reduced Ppw at 1.5 and 3 h, and Qva/Qt did not decrease as in Group P. We conclude that plasmapheresis-induced reduction in Ppw reduces the pulmonary capillary leak and venous admixture following acid aspiration, but this has the potentially adverse effect of reducing cardiac output and oxygen delivery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary edema: reversal by ultrafiltration

Ultrafiltration, the process by which plasma water is removed from the blood was utilized to determine its effect on lowering lung water in pulmonary edema produced by fluid overload, steam inhalation, and endotoxin. Lung water was measured by the thermal-dye indicator dilution technique which correlated well with lung water measured gravimetrically over a wide range (r = 0.95). Edema was produced by fluid overload in five mongrel dogs (Group I), by steam inhalation (Group II), and by endotoxin (Group III). Extravascular lung water (EVLW) rose significantly (P = less than 0.05) from control levels with the production of the edematous states (Group I: 8.0 ml/kg (mean) +/- 1.9 (SD) to 13.1 +/- 1.9); (Group II: 8.1 +/- 1.0 to 10.7 +/- 0.7); (Group III: 7.4 +/- 0.9 to 10.3 +/- 1.2). EVLW then fell significantly (P = less than 0.05) after ultrafiltration in all three groups (Group I: 8.9 +/- 2.4; Group II: 7.8 +/- 1.9; Group III: 7.7 +/- 1.4). Ultrafiltration was effective in reversing pulmonary edema and may have clinical application when excess lung water interferes with cardiac or pulmonary function.     

Effect of cardiac output on extravascular lung water estimates made with the Edwards lung water computer

The Edwards lung water computer system uses the thermal-dye indicator technique to estimate the lung extravascular fluid volume (EVLW). The authors tested the effect of changes in cardiac output (CO) on EVLW estimates made with the lung water computer in six dogs anesthetized with halothane. Baseline CO was 2.5 +/- 1.3 l/min (mean +/- SD); CO subsequently was increased either by 220% or decreased by 70% by either giving 0.5 mg/kg of isoproterenol or increasing the inspired halothane (1-4%), respectively. There was a significant correlation between the estimated EVLW and CO in each animal (P less than 0.05) such that a 50% decrease in CO from baseline caused an approximately 40% increase in estimated EVLW. Postmortem examination showed that the lungs were not edematous, even though the lung water computer data indicated that severe pulmonary edema had developed at reduced COs. At increased COs, estimated EVLW decreased. The authors conclude that the Edwards lung water computer overestimates lung water, possibly because the thermal indicator diffuses into nonpulmonary as well as pulmonary tissue. The overestimate is greatest at low cardiac outputs.     

Reduktion der Aggressivität der Beatmung nach Therapie eines Ölsäure-induzierten Lungenversagens durch Inhalation von Perfluorhexan

INTRODUCTION: The application of perfluorohexane (PFH) vapor led to an improvement of oxygenation and mechanical lung function in a model of oleic acid-induced ARDS in sheep. The aim of this study was to investigate the effects of PFH on gas exchange over an extended time period and to reduce the invasiveness of ventilation. METHOD: ARDS was induced in sheep ( n=12) by injecting 0.1 ml/kg body weight oleic acid intravenously. Six sheep were treated for 30 min with 18 vol.% PFH (PFH-Tx) and followed up over a time period of 240 min while untreated sheep ( n=6) served as controls. Subsequently the F(I)O(2) was reduced to generate a p(a)O(2) between 100-140 mmHg. Gas exchange, respiratory and hemodynamic data were collected at regular intervals. Data were analysed using covariance analysis. RESULTS: PFH treatment led to an improvement in oxygenation ( p<0.01) and in mechanical lung function ( p<0.01). Furthermore, mean pulmonary artery pressure ( p<0.01) and shunt ( p<0.01) were lower in PFH-Tx. F(I)O(2) could be reduced in all PFH-treated animals ( p<0.01). CONCLUSION: Treatment of oleic acid-induced lung injury with PFH vapor improved oxygenation and mechanical lung function over a extended time period allowing a reduction in the invasiveness of ventilation.     

Effects of oleic acid on pulmonary capillary leak and thromboxanes

The role of arachidonic acid metabolites in oleic acid-induced lung injury in anesthetized dogs was investigated. Oleic acid was administered as a bolus injection into the pulmonary artery in the following dose sequence: 0.05, 0.10, and 0.20 ml/kg at 30, 60, and 120 min, respectively, after either indomethacin (10 mg/kg iv) or vehicle. A control group (n = 3) received normal saline instead of oleic acid. Measurements of hemodynamic parameters, mean systemic (MAP), pulmonary capillary wedge, and pulmonary artery pressures (PAP), cardiac output, arterial blood gases, extravascular lung waters (EVLW) by thermaldye double indicator dilution techniques and plasma immunoreactive thromboxane B2 ( iTxB2 ), by radioimmunoassay were obtained at zero time (baseline) and 20 min following each oleic acid injection. A new noninvasive technique was employed to measure pulmonary capillary protein leak by the scintigraphic analysis of intravenously administered technetium-99m radiolabeled human serum albumin ( 99mTc -HSA) in the cardiac and lung regions. Oleic acid injection caused a significant dose related fall in MAP (P less than 0.0002), arterial pO2 (P less than 0.0001), and cardiac output (P less than 0.001), and increases in EVLW (P less than 0.003) and plasma iTxB2 (P less than 0.02) in the vehicle pretreated animals, while mean PAP remained unchanged. In contrast, in the indomethacin pretreated dogs, MAP, EVLW, cardiac output, and plasma iTxB2 levels did not change from baseline values and there was an increase in mean PAP. Pulmonary vascular resistance was significantly elevated (P less than 0.05) in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of pulmonary artery pressure on extravascular lung water in an experimental model of acute lung injury

BACKGROUND: Lung edema can be influenced by hemodynamic changes in pulmonary circulation. The aim of this study was to evaluate, in an experimental model of acute lung injury, the effect on extravascular lung water (EVLW) of an increase in pulmonary artery pressure (Ppa) without changes in cardiac output and wedge pressure. METHODS: Lung edema was produced by an intravenous oleic acid infusion in mixed-breed pigs weighing 25-31 kg, which, after 20 min, were randomly assigned to a control group (100% FiO(2)) (n = 6) or a high Ppa group (21% FiO(2)) (n = 7). An increase in pulmonary artery pressure of at least 40% over baseline was produced in the high Ppa group by alveolar hypoxia. Hemodynamic, ventilatory and gas exchange parameters were collected at regular intervals. Pulmonary, wedge and capillary pressures were measured with a pulmonary artery catheter and the occlusion technique. EVLW was calculated gravimetrically. RESULTS: At 240 min, both gravimetric-measured EVLW and mean pulmonary artery pressures were significantly higher (P < 0.05) in high Ppa animals vs. controls (12.06 +/- 4.21 vs. 7.98 +/- 2.46 ml/kg and 39.0 +/- 1.3 vs. 26.6 +/- 4.7 mmHg, respectively). Cardiac output (6.8 +/- 2.5 vs. 7.3 +/- 1.3) and pulmonary wedge pressures (9.2 +/- 1.7 vs. 9.4 +/- 2.8 mmHg) were similar. A difference was detected in pulmonary capillary pressures [17.0 +/- 3.3 (high Ppa) vs. 13.8 +/- 2.7 mmHg (controls)] but did not reach statistical significance. CONCLUSIONS: In this model, an increase in pulmonary artery pressure by alveolar hypoxia produces an increase in extravascular lung water, probably related to changes in pulmonary capillary pressures.     

Effect of furosemide on fully established low pressure pulmonary edema

It has been shown that furosemide, via nondiuretic vascular effects, reduces pulmonary shunt and lung water during the development of oleic acid permeability edema. We studied this effect in a fully established stable model of oleic acid permeability edema. Sixteen anesthetized mongrel dogs, mechanically ventilated with a FIO2 of 0.5, were studied 24 hr after induction of pulmonary capillary leak by intravenous oleic acid (0.06 cc/kg). After stabilization of pulmonary capillary wedge pressure (PCWP) in the range of 0.5-3 mm Hg, bilateral ureteral ligation was performed. Furosemide (2 mg/kg) was then administered intravenously to eight dogs (treated group). An equivalent volume of saline was given to eight control dogs (control group). Pulmonary artery (PAP) and capillary wedge pressures (PCWP), thermodilution cardiac output (Qt), thermal dye lung water (LW), venous admixture (Qva/Qt), arterial and mixed venous blood gases (PaO2, MVO2) were then measured at hourly intervals for 4 hr. During this period of time, central hemodynamics (PCWP, PAP, Qt) remained stable in both groups. Indices of gas exchange and edema formation (Qva/Qt, LW, PaO2) did not change significantly in either control or treated animals. We conclude that furosemide, previously shown to reduce pulmonary shunt and lung water in the early phase of oleic acid permeability edema, does not have any effect once the pulmonary injury is well-established.     

Effects of prolonged surgical trauma on the extravascular lung water and central blood volume in the dog

Extravascular lung water (EVLW) and central blood volume (CBV) were measured in 13 dogs with a double-indicator dilution technique (dye-cold), the indicators being detected intravascularly. Animals in a control group (n = 5) were mechanically ventilated for 8-15 h after baseline measurements. Another group of animals (n = 8) were subjected to extensive lymph duct cannulations, including a thoracoabdominal incision, and the dogs were followed for 8 to 18 h postoperatively. All dogs (n = 13) then received a dose of oleic acid intravenously in order to create lung damage. A positive fluid balance was maintained throughout the experiment. Basal EVLW was 8.8 ml/kg (n = 13) (similar in both groups), and did not change significantly in either group before oleic acid. Basal CBV was 18.5 ml/kg (n = 13); it increased (P less than 0.05) in the control group and decreased (P less than 0.05) in the surgery group during a 8-15-h period. EVLW was doubled (P less than 0.001) and CBV decreased slightly 2 h after oleic acid administration. The lung damage was similar in both groups, and was accompanied by increased pulmonary vascular pressures and marked reductions in arterial oxygen tension and thoracic compliance. The findings suggest that an earlier proposed dog model for the simultaneous measurement of EVLW and lymph flow can be used in long-term studies on lung fluid balance.     

Assessment of cardiac output,intravascular volume status,and extravascular lung water by transpulmonary indicator dilution in critically ill neonates and infants

OBJECTIVE: To assess cardiac output, intrathoracic blood volume, global end-diastolic volume, and extravascular lung water in critically ill neonates and small infants using transpulmonary indicator dilution. DESIGN: Prospective, observational, clinical study. SETTING: Pediatric intensive care unit in a university hospital. PARTICIPANTS: Critically ill neonates and small infants suffering from severe heart failure, respiratory failure, or sepsis (n = 10). INTERVENTIONS: A total of 194 transpulmonary indicator dilution measurements were done. Global end-diastolic volume, intrathoracic blood volume, and stroke volume were measured and compared with standard hemodynamic parameters during the clinical course and before and after volume loading (16 +/- 3.7 mL/kg of 10% albumin solution) in 8 of 10 patients. MEASUREMENTS AND MAIN RESULTS: A positive correlation was found for stroke volume index versus global end-diastolic volume (r = 0.76, p < 0.001) and intrathoracic blood volume (r = 0.56, p < 0.001). In contrast, no correlation was observed for stroke volume index versus central venous pressure. Volume loading resulted in significant increases in stroke volume index (p < 0.01), global end-diastolic volume (p < 0.01), and intrathoracic blood volume (p < 0.01); whereas central venous pressure, heart rate, mean arterial pressure, and extravascular lung water remained unchanged. CONCLUSION: Transpulmonary indicator dilution enables measurement of cardiac output and intravascular volume status in critically ill neonates and infants at the bedside. The effects of volume loading on cardiac preload and effective change in stroke volume can be monitored by this technique, whereas central venous pressure was not indicative of changes in intravascular volume status.     

Effect of ventilatory settings on accuracy of cardiac output measurement using partial CO(2) rebreathing.

BACKGROUND: Recently, a new device has been developed to measure cardiac output noninvasively using partial carbon dioxide (CO(2)) rebreathing. Because this technique uses CO(2) rebreathing, the authors suspected that ventilatory settings, such as tidal volume and ventilatory mode, would affect its accuracy: they conducted this study to investigate which parameters affect the accuracy of the measurement. METHODS: The authors enrolled 25 pharmacologically paralyzed adult post-cardiac surgery patients. They applied six ventilatory settings in random order: (1) volume-controlled ventilation with inspired tidal volume (V(T)) of 12 ml/kg; (2) volume-controlled ventilation with V(T) of 6 ml/kg; (3) pressure-controlled ventilation with V(T) of 12 ml/kg; (4) pressure-controlled ventilation with V(T) of 6 ml/kg; (5) inspired oxygen fraction of 1.0; and (6) high positive end-expiratory pressure. Then, they changed the maximum or minimum length of rebreathing loop with V(T) set at 12 ml/kg. After establishing steady-state conditions (15 min), they measured cardiac output using CO(2) rebreathing and thermodilution via a pulmonary artery catheter. Finally, they repeated the measurements during pressure support ventilation, when the patients had restored spontaneous breathing. The correlation between two methods was evaluated with linear regression and Bland-Altman analysis. RESULTS: When VT was set at 12 ml/kg, cardiac output with the CO(2) rebreathing technique correlated moderately with that measured by thermodilution (y = 1.02x, R = 0.63; bias, 0.28 l/min; limits of agreement, -1.78 to +2.34 l/min), regardless of ventilatory mode, oxygen concentration, or positive end-expiratory pressure. However, at a lower VT of 6 ml/kg, the CO(2) rebreathing technique underestimated cardiac out-put compared with thermodilution (y = 0.70x; R = 0.70; bias, -1.66 l/min; limits of agreement, -3.90 to +0.58 l/min). When the loop was fully retracted, the CO(2) rebreathing technique overestimated cardiac output. CONCLUSIONS: Although cardiac output was underreported at small VT values, cardiac output measured by the CO(2) rebreathing technique correlates fairly with that measured by the thermodilution method.     

Furosemide, when used in combination with positive end-expiratory pressure, facilitates the resorption of extravascular lung water in experimental hydrostatic pulmonary oedema

The study aimed to establish whether furosemide given intravenously improved resorption of hydrostatic pulmonary oedema in 14 dogs mechanically ventilated with positive end-expiratory pressure (PEEP). Hydrostatic pulmonary oedema was created by simultaneous inflation of a left atrial balloon and rapid intravenous infusion of isotonic saline. The hydrostatic process was terminated by deflating the balloon and reducing the infusion rate. A PEEP of 10 cmH2O (1.0 kPa) was applied in all animals; in seven, furosemide was administered (diuretic group), 1 mg/kg intravenously as a bolus followed by an infusion of 0.5 mg/kg per hour, while the remaining seven dogs served as a control group. All dogs were studied for a period of 4 h. The extravascular lung water measured with the double indicator dilution technique was 28.3 +/- 3.8 (diuretic group) and 28.2 +/- 6.8 ml/kg (control group) during maximum oedema. It was reduced to 16.4 +/- 2.2 (diuretic group) vs 19.8 +/- 3.7 ml/kg (control group) after 4 h of resorption, P less than 0.05. Postmortem gravimetric values of extravascular lung water were 9.1 +/- 3.4 (diuretic group) vs 12.6 +/- 5.0 g/kg (control group). In the diuretic group the urinary output increased threefold, and haemoglobin and serum protein concentrations were higher than in the control group. There was a significantly greater decrease in cardiac output and central blood volume in the diuretic group. In conclusion, furosemide given intravenously improved lung fluid resorption in hydrostatic pulmonary oedema, probably by increasing the plasma colloid osmotic pressure.     

雾化吸入和静脉注射米力农对大鼠急性肺损伤疗效的比较

目的 比较雾化吸入和静脉注射米力农对大鼠急性肺损伤(ALI)的疗效.方法 SD大鼠40只,体重300～350 g,随机分为4组(n=10):对照组(Ⅰ组)、ALI组(Ⅱ组)、米力农雾化吸入组(Ⅲ组)和米力农静脉注射组(Ⅳ组).Ⅰ组经右颈外静脉插管注入0.1%BSA溶液2 ml/kg;Ⅱ组经20 min注入油酸混悬液2 ml/kg;Ⅲ组注入油酸后30 min雾化吸入1 mg/ml米力农10 min,每60分钟重复一次,共4次;Ⅳ组注入油酸后30 min经右颈外静脉注射米力农10 μg/kg,然后静脉输注米力农1 μg·kg-1·min-1 10min,每60分钟重复一次,共4次.各组于第4次治疗结束后放血处死大鼠.于治疗开始即刻、第1次治疗时、第2次治疗时、第3次治疗时和第4次治疗时,记录平均动脉压(MAP)和肺动脉压(PAP),测定动脉血气和混合静脉血气,计算氧合指数(PaO2/FiO2)和肺内分流率(Qs/Qt).回收支气管肺泡灌洗液(BALF),进行中性粒细胞计数,采用Bradford法测定蛋白浓度;测定肺组织湿,干重比(W/D)和髓过氧化物酶(MPO)活性;观察肺组织超微结构.结果 与Ⅲ组比较,Ⅳ组第3次治疗和第4次治疗时MAP和Pa02/FiO2降低,第4次治疗时PAP和Qs/Qt升高,BALF蛋白浓度、中性粒细胞计数和肺组织W/D、MPO活性均升高(P＜0.05).结论 雾化吸入米力农减轻大鼠ALI的作用优于静脉注射米力农,对血液动力学影响小.     

Noninvasive cardiac output measurement using partial carbon dioxide rebreathing is less accurate at settings of reduced minute ventilation and when spontaneous breathing is present

BACKGROUND: Although evaluation of cardiac output by the partial carbon dioxide rebreathing technique is as accurate as thermodilution techniques under controlled mechanical ventilation, it is less accurate at low tidal volume. It is not clear whether reduced accuracy is due to low tidal volume or low minute ventilation. The effect of spontaneous breathing on the accuracy of partial carbon dioxide rebreathing measurement has not been fully investigated. The objectives of the current study were to investigate whether tidal volume or minute ventilation is the dominant factor for the accuracy, and the accuracy of the technique when spontaneous breathing effort is present. METHODS: The authors enrolled 25 post-cardiac surgery patients in two serial protocols. First, the authors applied three settings of controlled mechanical ventilation in random order: large tidal volume (12 ml/kg), the same minute ventilation with a small tidal volume (6 ml/kg), and 50% decreased minute ventilation with a small tidal volume (6 ml/kg). Second, when the patient recovered spontaneous breathing, the authors applied three conditions of partial ventilatory support in random order: synchronized intermittent mandatory ventilation-pressure support ventilation, pressure support ventilation with an appropriately adjusted rebreathing loop, and pressure support ventilation with the shortest available loop. After establishing steady state conditions, the authors measured cardiac output using both partial carbon dioxide rebreathing and thermodilution methods. The correlation between the data yielded by the two methods was determined by Bland-Altman analysis and linear regression. RESULTS: Cardiac output with the carbon dioxide rebreathing technique correlated moderately with that measured by thermodilution when minute ventilation was set to maintain normocapnia, regardless of tidal volumes. However, when minute ventilation was set low, the carbon dioxide rebreathing technique underreported cardiac output (y = 0.70x; correlation coefficient, 0.34; bias, -1.73 l/min; precision, 1.27 l/min; limits of agreement, -4.27 to +0.81 l/min). When there was spontaneous breathing, the correlation between the two cardiac output measurements became worse. Carbon dioxide rebreathing increased spontaneous tidal volume and respiratory rate (20% and 30%, respectively, during pressure support ventilation) when the rebreathing loop was adjusted for large tidal volume. CONCLUSIONS: During controlled mechanical ventilation, minute ventilation rather than tidal volume affected the accuracy of cardiac output measurement using the partial carbon dioxide rebreathing technique. When spontaneous breathing is present, the carbon dioxide rebreathing technique is less accurate and increases spontaneous tidal volume and respiratory rate.     

Effect of Ventilatory Settings on Accuracy of Cardiac Output Measurement Using Partial CO2 Rebreathing

Background: Recently, a new device has been developed to measure cardiac output noninvasively using partial carbon dioxide (CO2) rebreathing. Because this technique uses CO2 rebreathing, the authors suspected that ventilatory settings, such as tidal volume and ventilatory mode, would affect its accuracy: they conducted this study to investigate which parameters affect the accuracy of the measurement.

Methods: The authors enrolled 25 pharmacologically paralyzed adult post-cardiac surgery patients. They applied six ventilatory settings in random order: (1) volume-controlled ventilation with inspired tidal volume (VT) of 12 ml/kg; (2) volume-controlled ventilation with VT of 6 ml/kg; (3) pressure-controlled ventilation with VT of 12 ml/kg; (4) pressure-controlled ventilation with VT of 6 ml/kg; (5) inspired oxygen fraction of 1.0; and (6) high positive end-expiratory pressure. Then, they changed the maximum or minimum length of rebreathing loop with VT set at 12 ml/kg. After establishing steady-state conditions (15 min), they measured cardiac output using CO2 rebreathing and thermodilution via a pulmonary artery catheter. Finally, they repeated the measurements during pressure support ventilation, when the patients had restored spontaneous breathing. The correlation between two methods was evaluated with linear regression and Bland-Altman analysis.

Results: When VT was set at 12 ml/kg, cardiac output with the CO2 rebreathing technique correlated moderately with that measured by thermodilution (y = 1.02x, R = 0.63; bias, 0.28 l/min; limits of agreement, -1.78 to +2.34 l/min), regardless of ventilatory mode, oxygen concentration, or positive end-expiratory pressure. However, at a lower VT of 6 ml/kg, the CO2 rebreathing technique underestimated cardiac out-put compared with thermodilution (y = 0.70x; R = 0.70; bias, -1.66 l/min; limits of agreement, -3.90 to +0.58 l/min). When the loop was fully retracted, the CO2 rebreathing technique overestimated cardiac output.