Effect of a catecholamine-induced increase in cardiac output on extravascular lung water

OBJECTIVE: To determine the influence of dopamine- and dobutamine-induced increases in cardiac output on the extravascular lung water in an experimental model of pulmonary edema. DESIGN: Animal experimental study. SETTING: Animal experimental laboratory of a tertiary hospital. SUBJECTS: Mixed-race pigs (n = 20) weighing 28-32 kg. INTERVENTIONS: After the animals were anesthetized and tracheotomized, they were injected with 0.1 mL/kg of oleic acid, producing a pulmonary edema by increased permeability. The animals then were randomized into two groups: Group I (n = 10) received no medication to alter cardiac output and remained on mechanical ventilation during the 240 mins of the experiment; group II (n = 10) received a continuous infusion of dopamine and dobutamine to produce a cardiac output increase of >or=30% the basal value and underwent the same mechanical ventilation regimen as group I. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and respiratory variables were measured at 0 (baseline) and 30, 60, 120, 180, and 240 mins after the infusion of oleic acid. At 30 mins, the cardiac output of group II (5.40 +/- 0.94 L/min) was significantly (p < .005) higher than that of group I (3.65 +/- 1.02 L/min), and a similar significant increase was recorded at all measurement times until the end of the experiment. The mean pulmonary arterial pressure was similar in both groups except that at 240 mins it was significantly higher in group I (normal cardiac output) than in group II (high cardiac output; 34.9 +/- 7.9 mm Hg vs. 27.2 +/- 3.8 mm Hg, p = .01). The extravascular lung water was calculated by gravimetric method after the death of the animal. The extravascular lung water of group I (13.8 +/- 3.6 mL/kg) did not significantly differ from that of group II (11.5 +/- 4.0 mL/kg). CONCLUSIONS: An increase in cardiac output experimentally produced by the infusion of dopamine and dobutamine does not modify the amount of extravascular lung water.     

Atrial natriuretic peptide improves pulmonary gas exchange by reducing extravascular lung water in canine model with oleic acid-induced pulmonary edema

OBJECTIVE: The purpose of this study was to examine and compare the effects of atrial natriuretic peptide and furosemide on pulmonary gas exchange, hemodynamics, extravascular lung water, and renal function in a dog model of oleic acid-induced pulmonary edema. DESIGN: Prospective, comparable, experimental study. SETTING: Laboratory at a university hospital. SUBJECTS: Eighteen male beagle dogs were studied under mechanical ventilation with pentobarbital anesthesia. INTERVENTIONS: Oleic acid (0.08 mL/kg) was injected and allowed for 1 hr to achieve pulmonary edema with hypoxemia at Fio2 of 0.3. After lung injury, dogs were divided into three groups; control group (n = 6) receiving saline (2.5 mL/hr for 5 hrs), atrial natriuretic peptide group (n = 6) receiving atrial natriuretic peptide (1 microg x kg(-1) x min(-1) for 5 hrs), and furosemide group (n = 6) receiving furosemide (1 mg x kg(-1) x hr(-1) for 5 hrs). MEASUREMENTS AND MAIN RESULTS: Hemodynamics, arterial blood gases, extravascular lung water, and renal function were measured hourly for 7 hrs after injury. Oleic acid increased extravascular lung water and induced hypoxemia. In the atrial natriuretic peptide group, extravascular lung water was significantly (p <.05) lower and Pao2 was significantly (p <.05) higher than in the control and furosemide groups, respectively. Pulmonary hypertension induced by oleic acid was attenuated by atrial natriuretic peptide infusion but not by saline or furosemide. Increased natriuresis/diuresis did not significantly differ between the atrial natriuretic peptide and the furosemide group, whereas creatinine clearance in the atrial natriuretic peptide group was significantly higher than that in the furosemide group. CONCLUSIONS: These findings suggest that atrial natriuretic peptide improves pulmonary gas exchange by reducing extravascular lung water and pulmonary arterial pressure, possibly independently from natriuresis/diuresis in oleic acid-induced pulmonary edema.     

Effect of high-dose prednisolone on lung fluid in patients with non-cardiogenic lung edema

The influence of high-dose prednisolone on extravascular lung water (EVLW) was studied in a randomized trial in patients with noncardiac pulmonary edema. The patients were treated every 6 hours for 48 hours with 2 g of prednisolone-hemisuccinate or placebo. In the prednisolone-group (n = 7) EVLW decreased from 16.4 +/- 6.2 before to 11.8 +/- 5.1 ml/kg after treatment (p less than 0.05). Additionally alveolar-arterial oxygen gradient (AaDO2/FiO2), pulmonary vascular resistance and heart rate decreased, while arterial oxygen tension (PaO2/FiO2) and mean arterial pressure increased (p less than 0.05). In the placebo-group (n = 7) EVLW increased slightly from 17.5 +/- 3.1 before to 19.3 +/- 10.3 ml/kg after treatment. Additionally all other parameters did not change significantly in this group. Although no statistical significant difference was found between the two groups of treatment, a decrease in EVLW was observed in all prednisolone-treated patients, whereas a pronounced increase in EVLW was found in 3 placebo-treated patients. Probably, those patients would have benefited from high-dose prednisolone treatment. High-dose prednisolone reduced EVLW and improved hemodynamics and gas exchange in patients with noncardiac pulmonary edema, whereas placebo did not achieve comparable effects. Therefore, high-dose prednisolone appears beneficial in noncardiac pulmonary edema in respect of EVLW, hemodynamics, and gas exchange.     

Accuracy of transpulmonary thermodilution versus gravimetric measurement of extravascular lung water

OBJECTIVE: Pulmonary edema is a severe and often life-threatening condition. The diagnosis of pulmonary edema and its quantification have great clinical significance and yet can be difficult. A new technique based on thermodilution measurement using a single indicator has recently been developed (PiCCO, Pulsion Medical Systems, AG Germany). This method allows the measurement of extravascular lung water and thus can quantify degree of pulmonary edema. The technique has not been compared with a gold standard, gravimetric measurement of extravascular lung water. Therefore, the objective of this study was to determine the ability of extravascular lung water measurement with the PiCCO to reflect the extravascular lung water as measured with a gravimetric technique in a dog model of pulmonary edema. DESIGN: Prospective, randomized animal study. SETTING: A university animal research laboratory. SUBJECTS: Fifteen mongrel dogs (n = 5/group) weighing 20-30 kg. INTERVENTIONS: The dogs were anesthetized and mechanically ventilated. Five dogs served as controls; in five dogs hydrostatic pulmonary edema was induced using inflation of a left atrial balloon combined with fluid administration to maintain a high pulmonary artery occlusion pressure; and in five dogs pulmonary edema was induced by intravenous injection of oleic acid. After a period of stabilization in a state of pulmonary edema, extravascular lung water was measured with the PiCCO monitor. The animals were then killed, and extravascular lung water was measured using a gravimetric technique. MEASUREMENTS AND MAIN RESULTS: There was a very close (r =.967, p <.001) relationship between transpulmonary thermodilution and gravimetric measurements. The measurement with the PiCCO was consistently higher, by 3.01 +/- 1.34 mL/kg, than the gravimetric measurement. CONCLUSIONS: Measurement of extravascular lung water using transpulmonary thermodilution with a single indicator is very closely correlated with gravimetric measurement of lung water in both increased permeability and hydrostatic pulmonary edema.     

Immediate application of positive-end expiratory pressure is more effective than delayed positive-end expiratory pressure to reduce extravascular lung water

OBJECTIVE: To determine by the measurement of extravascular lung water (EVLW) whether the timing of positive-end expiratory pressure (PEEP) application influences the intensity of lung injury. DESIGN: Animal experimental study. SETTING: Animal experimental laboratory. SUBJECTS: Mixed-breed pigs (n = 18), aged 4 to 5 mos, weighing 25 to 30 kg. INTERVENTIONS: The animals were anesthetized and tracheotomized, after which a permeability pulmonary edema was instigated by infusing oleic acid (0.1/kg) into the central vein. All animals were then randomly divided into three groups. In group 1 (n = 5), 10 cm H2O of PEEP was applied immediately after the oleic acid infusion and maintained throughout the 6 hrs of the experiment. Group 2 (n = 7) received the same level of PEEP 120 mins after the insult for 4 hrs. Group 3 (n = 6), the control group, was ventilated without PEEP for the six hrs of the experiment. MEASUREMENTS AND MAIN RESULTS: At the end of the experiment, EVLW was calculated by gravimetric method. EVLW in group 1 (11.46+/-2.00 mL/kg) was significantly less than in group 2 (19.12+/-2.62 mL/kg) and group 3 (25.81+/-1.57 mL/kg), (p<.0001). Oxygenation also showed important differences by the end of the experiment when the Pao2/Fio2 ratio was significantly better in group 1 (467+/-73) than in group 2 (180+/-82) and group 3 (39+/-9), (p<.0001). CONCLUSIONS: The application of 10 cm H2O of PEEP reduces EVLW in a time-dependent manner and maximum protective effect is achieved if it is applied immediately after lung injury production.     

Extravascular lung water after pneumonectomy and one-lung ventilation in sheep

OBJECTIVE: To compare the single thermodilution and the thermal-dye dilution techniques with postmortem gravimetry for assessment of changes in extravascular lung water after pneumonectomy and to explore the evolution of edema after injurious ventilation of the left lung. DESIGN: Experimental study. SETTING: University laboratory. SUBJECTS: A total of 30 sheep weighing 35.6 +/- 4.6 kg. The study included two parts: a pneumonectomy study (n = 18) and an injurious ventilation study (n = 12). METHODS: Sheep were anesthetized and mechanically ventilated with an FiO2 of 0.5, tidal volume of 6 mL/kg, and positive end-expiratory pressure of 2 cm H2O. In the pneumonectomy study, sheep were assigned to right-sided pneumonectomy (n = 7), left-sided pneumonectomy (n = 7), or lateral thoracotomy only (sham operation, n = 4). In the injurious ventilation study, right-sided pneumonectomy was followed by ventilation with a tidal volume of 12 mL/kg and positive end-expiratory pressure of 0 cm H2O (n = 6) or by ventilation with a tidal volume of 6 mL/kg and positive end-expiratory pressure of 2 cm H2O for 4 hrs (n = 6). Volumetric variables, including extravascular lung water index (EVLWI), were measured with single thermodilution (STD; EVLWI(STD)) and thermal-dye dilution (TDD; EVLWI(TDD)) techniques. We monitored pulmonary hemodynamics and respiratory variables. After the sheep were killed, EVLWI was determined for each lung by gravimetry (EVLWI(G)). RESULTS: In total, the study yielded strong correlations of EVLWI(STD) and EVLWI(TDD) with EVLWI(G) (n = 30; r = .83 and .94, respectively; p < .0001). After pneumonectomy, both the left- and the right-sided pneumonectomy groups displayed significant decreases in EVLWI(STD) and EVLWI(TDD). The injuriously ventilated sheep demonstrated significant increases in EVLWI that were detected by both techniques. The mean biases (+/-2 SD) compared with EVLWI(G) were 3.0 +/- 2.6 mL/kg for EVLWI(STD) and 0.4 +/- 1.6 mL/kg for EVLWI(TDD). CONCLUSIONS: After pneumonectomy and injurious ventilation of the left lung, TDD and STD displayed changes in extravascular lung water with acceptable accuracy when compared with postmortem gravimetry. Ventilator-induced lung injury seems to be a crucial mechanism of pulmonary edema after pneumonectomy.     

Measurement of pulmonary edema in patients with acute respiratory distress syndrome

OBJECTIVE: We measured pulmonary edema by thermal indocyanine green-dye double-dilution technique and quantitative computed tomography (CT) in patients with acute respiratory distress syndrome and compared the two techniques. DESIGN AND SETTING: Prospective human study in a university hospital. PATIENTS: Fourteen mechanically ventilated patients with acute respiratory distress syndrome (nine primary; nine with intubation <7 days). INTERVENTIONS: All patients underwent a spiral CT of the thorax. We measured pulmonary thermal volume (PTV) and its components, extravascular lung water and pulmonary blood volume, with an integrated fiberoptic monitoring system (COLD Z-021). MEASUREMENTS AND RESULTS: PTV was tightly correlated with lung weight (LW) measured by CT (PTV = 0.6875 * LW(CT) + 292.77; correlation coefficient = 0.91; p < .0001; bias -11 +/- 8 %). Neither etiology of acute respiratory distress syndrome (primary vs. secondary) nor days of intubation affected the accuracy of thermal dye dilution in comparison with CT. There was no correlation between the extravascular lung water (12.3 +/- 3.4 mL/kg) and CT distribution of lung tissue compartments. Extravascular lung water and pulmonary blood volume showed good reproducibility in 32 pairs of thermal dye dilution measurements. CONCLUSIONS: Measurements of lung edema by thermal indocyanine green-dye double-dilution method show good correlation with those by quantitative computed tomography and good reproducibility in patients with acute respiratory distress syndrome.     

不同容量平衡盐液对初进高原大鼠失血性休克合并肺水肿的复苏效果

目的 :探讨不同容量平衡盐液对初进高原大鼠失血性休克合并肺水肿的复苏效果 ,明确其液体复苏有效量及限量。方法 :初进高原 (西藏拉萨 ) SD大鼠 12 6只 ,戊巴比妥钠麻醉 ,维持血压 5 0 m m Hg( 1mm Hg=0 .133 k Pa) 1h加油酸 ( 5 0μl/ kg)静脉注射复制失血性休克合并肺水肿模型 (正常对照组不放血、不给油酸 )。第一部分实验 6 3只大鼠分为正常对照组、单纯失血性休克不复苏组、失血性休克合并肺水肿不复苏组、失血性休克合并肺水肿输注失血量 0 .5倍、1倍、1.5倍、2倍和 3倍的乳酸林格氏液 ( L R)和 1倍失血量 L R加甘露醇( 10 m l/ kg)组 ,观察液体输注后 15、30、6 0和 12 0 m in的血流动力学指标变化 ,30和 12 0 min的血气指标变化和 12 0 min肺、脑含水量变化 ,每组 7只动物。第二部分实验观察不同容量 L R输注对休克大鼠存活时间的影响。结果 :0 .5倍容量 L R输注可明显改善休克大鼠平均动脉压 ( MAP)、左心室内压 ( L VSP)和左心室内压最大变化速率 (± dp/ dt max)等血流动力学指标 ,延长存活时间 ( P均 <0 .0 1) ,不增加休克动物肺、脑含水量 ,对血气指标无明显影响 ;1倍容量 L R输注可轻度改善休克动物血流动力学指标 ,轻度延长存活时间 ,增加肺含水量 ,对血气指标无显著影响 ;1.5倍、 2倍     

Pulmonary extravascular water in patients with acute respiratory failure

The purpose of the investigation was to study pulmonary extravascular water levels and pulmonary vascular permeability (PVP) in the pathogenesis of acute respiratory failure (ARF)/acute respiratory distress syndrome (ARDS). Twenty-nine patients with ARF/ARDS and 10 healthy volunteers were examined. Central hemodynamics and oxygen transport were explored, by using a Swan-Ganz catheter. Intrathoracic volemic parameters were studied by the transpulmonary thermodilution technique. PVP was assessed by the pulmonary 67Ga-labelled transferrin leakage index. Plasma colloid osmotic pressure (COP) was measured on an osmometer. In most patients with ARF/ARDS, the pulmonary extravascular water index (PEVWI) was found to be higher (mean 16.9 +/- 1.5 ml/kg). At the same time its value was not greater than 10 ml/kg in 7 (24%) of 29 patients. There were no correlations between PEVWI and PaO2/FiO2 and between pulmonary extravascular water and AaDO2. The PVP index (PVPI) measured by transpulmonary thermodilution was 3.2 +/- 0.2, it being normal in 13 (45%) out of 29 patients. The pulmonary 67Ga-transferrin leakage index was higher in all the patients than in healthy individuals (23.2 +/- 2.9 x 10(-3) vs 5.7 +/- 9.9 x 10(-3)) and correlated with PaO2/FiO2 (r = 0.71; p = 0.01). In patients with ARF/ARDS, COP was lower (19.9 +/- 0.7 mm Hg). There were correlations between COP and PEVWI (r = -0.34; p = 0.01), COP and PVPI (r = -0.40; p = 0.044), COP and PaO2/FiO2 (r = 0.35; p = 0.02). PEVWI correlated with the COP-pulmonary wedge pressure gradient (r = -0.45; p = 0.0024). Hypoxemia correlated with intrapulmonary shunt (Qs/Qt). There was no relationship between Qs/Qt and PEVWI in the group as a whole. According to the ratio of Qs/Qt to PEVWI, the patients were divided into 2 groups. Group 1 comprised 11 patients with the ratio < or = 2; Group 2 included 18 patients with the ratio > or = 2, i.e. with an unproportional shunt enlargement as to the severity of pulmonary edema. A correlation between Qs/Qt and PEVWI was found in both groups: r = 0.82; p = 0.001 with the ratio < or = 2 and r = 0.48; p = 0.04 with the ratio > or = 2. Diverse causes of shunt formation were histologically detected. Thus, pulmonary edema was not identified in 24% of patients with ARF/ARDS. Arterial hypoxemia is associated with the increase in the shunt, but, in a portion of patients, the shunt was caused with atelectasis unassociated with pulmonary edema. Increased pulmonary permeability for transferrin is detectable in ARF/ARDS irrespective the severity of pulmonary edema. The pathogenetic features of lung lesions should be taken into account while choosing a treatment for ARF/ARDS.     

HSD is a better resuscitation fluid for hemorrhagic shock with pulmonary edema at high altitude

To investigate the fluid tolerance of hemorrhagic shock with pulmonary edema (HSPE) at high altitude in unacclimated rats and the beneficial effect of 7.5% hypertonic saline/6% dextran (HSD). One hundred seventy-six Sprague-Dawley rats, transported to LaSa, Tibet, 3,760 m above the sea level, were anesthetized with sodium pentobarbital (30 mg/kg, i.p.) within 1 week. Hemorrhagic shock with pulmonary edema was induced by bloodletting (50 mmHg for 1 h) plus intravenous injection of oleic acid (50 microL/kg). Seventy-seven rats were equally divided into 11 groups (n = 7/group) including sham-operated control group; hemorrhagic shock control group; HSPE control group; HSPE plus 0.5-, 1.0-, 1.5-, 2.0-, or 3.0-fold volumes of lactated Ringer's solution (LR) groups; and HSPE plus 4, 6, and 8 mL/kg of HSD groups. Hemodynamic parameters including mean arterial blood pressure, left intraventricular systolic pressure, and the maximal change rate of intraventricular pressure rise or decline (+/-dp/dtmax) were observed at baseline and at 15, 30, 60, and 120 min after infusion; blood gases were measured at 30 and 120 min after infusion, and the water content of lung and brain was determined at 120 min after infusion. Additional 99 rats were used to observe the effect of these treatments on the survival time of HSPE rats; 0.5 volume of LR infusion slightly increased the mean arterial blood pressure, left intraventricular systolic pressure, and +/-dp/dtmax and prolonged the survival time of HSPE animals as compared with the HSPE group (P < 0.05 - 0.01); it did not increase the water content of lung and brain and had no marked influences on blood gases. One volume of LR infusion had somewhat improved the hemodynamic parameters for HSPE animals, but had no apparent effect on the survival time and the water content of lung and brain. Lactate Ringer's solution infusion, 1.5, 2, and 3 volumes, significantly deteriorated the hemodynamic parameters, increased the water content of lung, and decreased the survival time of HSPE animals. Hypertonic saline/6% dextran (4 - 8 mL/kg) significantly increased the hemodynamic parameters, improved the blood gases, decreased the water content of lung and brain, and prolonged the survival time of HSPE rats. Among the three dosages of HSD, 6 mL/kg of HSD had the best effect. The tolerance of fluid infusion for hemorrhagic shock with pulmonary edema at high altitude is significantly decreased. More than one volume of LR infusion would aggravate the pulmonary edema and exacerbate the resuscitation effect, but only one volume of LR cannot reach the effective volume resuscitation. Small volume of HSD could better resuscitate hemorrhagic shock with pulmonary edema at high altitude.     

Lung fluid dynamics and supply dependency of oxygen uptake during experimental endotoxic shock and volume resuscitation

BACKGROUND AND METHODS: We studied the effect of volume resuscitation on lung fluid balance and systemic oxygen extraction during septic shock in eight anesthetized dogs. Sepsis was induced using a 2-hr continuous infusion of Escherichia coli endotoxin at 0.25 micrograms/min.kg. Relationships between oxygen uptake (VO2) and oxygen supply (DO2) were performed acutely during stepwise controlled decrements in cardiac output by progressive inflation of an intracardiac balloon. At each stage, DO2 and corresponding VO2 were measured independently and the individual critical DO2 level was referred to as the point below which the relationship held. The slope of such a constructed relationship was defined as the maximal oxygen extraction ratio. Lung fluid balance was assessed by measurements of extravascular lung water. All values were studied at baseline, after endotoxin insult, and after reversing hypotension by a 10% dextran infusion. RESULTS: Endotoxin infusion led to a shock state that associated hypotension (from 135 to 63 mm Hg) with increases in blood lactate (from 0.53 to 3.9 mmol/L). The mean critical DO2 and maximal oxygen extraction ratio were significantly altered from 7.9 to 17.8 mL/min.kg and from 0.81 to 0.38, respectively. After reversing hypotension by 28 mL/kg colloid infusion, the critical DO2 (11.4 mL/min.kg) and maximal oxygen extraction ratio (0.48) were significantly improved. However, restoration of normal values required a state of fluid overload by further dextran infusion (8 mL/kg). At the end of the fluid challenge, extravascular lung water significantly increased from 6.4 to 17.4 mL/kg. CONCLUSIONS: These data suggest that volume loading may reverse endotoxin-induced peripheral perfusion abnormalities. However, substantial pulmonary edema may occur, possibly jeopardizing the beneficial effects of fluid expansion.     

Intermittent outpatient nesiritide infusion reduces hospital admissions in patients with advanced heart failure

Recombinant B-type natriuretic peptide (BNP) is a therapeutic modality in patients with decompensated congestive heart failure. Retrospectively tested are the effects of intermittent outpatient nesiritide infusion on symptoms, hospital readmission rates, endogenous BNP, and renal function in patients with advanced heart failure. Twenty-four patients in heart failure in New York Heart Association (NYHA) classes III-IV received a 6- to 8-hour intermittent nesiritide outpatient infusion (0.01 mcg/kg/min continuously intravenously) once weekly for a total duration of 3 months in addition to standard medical therapy. Data were analyzed retrospectively to compare hospital readmission rates, endogenous BNP levels, blood urea nitrogen, and creatinine levels 1 year before and up to 12 months after starting treatment. All patients tolerated nesiritide infusions well with no significant adverse events. At the end of the observation period, NYHA classes had improved 1 class in 16 patients and 2 classes in 4 patients and remained unchanged in 4 patients. There was a significant reduction in hospital readmissions within 1 year with nesiritide treatment compared with the year before (0.94 +/- 0.8 vs 3.6 +/- 2.2, P < .005). No significant changes were seen regarding endogenous BNP levels (1002 +/- 870 vs 1092 +/- 978 pg/mL, P = .95), blood urea nitrogen levels (45 +/- 28 vs 45 +/- 26 mg/dL, P = .96), and a tendency of slightly elevated creatinine levels that did not differ significantly compared with prior levels (1.76 +/- 0.85 vs 1.1 +/- 0.56 mg/dL, P = .5). Intermittent outpatient nesiritide treatment resulted in improved symptoms and reduced hospital readmission rates without a significant decline in renal function in patients with advanced heart failure but did not alter endogenous BNP levels.     

Effects of antihistamines on the lung vascular response to histamine in unanesthetized sheep. Diphenhydramine prevention of pulmonary edema and increased permeability.

To see whether antihistamines could prevent and reverse histamine-induced pulmonary edema and increased lung vascular permeability, we compared the effects of a 4-h intravenous infusion of 4 mug/kg per min histamine phosphate on pulmonary hemodynamics, lung lymph flow, lymph and plasma protein content, arterial blood gases, hematocrit, and lung water with the effects of an identical histamine infusion given during an infusion of diphenhydramine or metiamide on the same variables in unanesthetized sheep. Histamine caused lymph flow to increase from 6.0+/-0.5 to 27.0+/-5.5 (SEM) ml/h (P less than 0.05), lymph; plasma globulin concentration ratio to increase from 0.62+/-0.01 to 0.67+/-0.02 (P less than 0.05), left atrial pressure to fall from 1+/-1 to -3+/-1 cm H2O (P less than 0.05), and lung lymph clearance of eight protein fractions ranging from 36 to 96 A molecular radius to increase significantly. Histamine also caused increases in lung water, pulmonary vascular resistance, arterial PCO2, pH, and hematocrit, and decreases in cardiac output and arterial PO2. Diphenhydramine (3 mg/kg before histamine followed by 1.5 mg/kg per h intravenous infusion) completely prevented the histamine effect on hematocrit, lung lymph flow, lymph protein clearance, and lung water content, and reduced histamine effects on arterial blood gases and pH. 6 mg/kg diphenhydramine given at the peak histamine response caused lymph flow and lymph: plasma protein concentration ratios to fall. Metiamide (10 mg/kg per h) did not affect the histamine lymph response. We conclude that diphenhydramine can prevent histamine-induced pulmonary edema and can prevent and reverse increased lung vascular permeability caused by histamine, and that histamine effects on lung vascular permeability are H1 actions.     

Prolonged alveolocapillary barrier damage after acute cardiogenic pulmonary edema

OBJECTIVES: To determine whether acute cardiogenic pulmonary edema is associated with damage to the alveolocapillary barrier, as evidenced by increased leakage of surfactant specific proteins into the circulation, to document the duration of alveolocapillary barrier damage in this setting, and to explore the role of pulmonary parenchymal inflammation by determining if circulating tumor necrosis factor-alpha is increased after acute cardiogenic pulmonary edema. DESIGN: Prospective, observational study. SETTING: Critical care, cardiac intensive care, and cardiology wards of a tertiary-care university teaching hospital. PATIENTS: A total of 28 patients presenting with acute cardiogenic pulmonary edema and 13 age-matched normal volunteers. INTERVENTIONS: Circulating surfactant protein-A and -B and tumor necrosis factor-alpha were measured on days 0 (presentation), 1, 3, 7, and 14. Clinical markers of pulmonary edema were documented at the same times. MEASUREMENTS AND MAIN RESULTS: Surfactant protein-A and -B were elevated on day 0 compared with controls (367 +/- 17 ng/mL vs. 303 +/- 17 and 3821 +/- 266 ng/mL vs. 2747 +/- 157 [mean +/- sem], p <.05), and although clinical, hemodynamic and radiographic variables improved rapidly (p <.001), surfactant protein-A and -B rose further until day 3 (437 +/- 22, p <.001, 4642 +/- 353, p <.01). Tumor necrosis factor-alpha was elevated at presentation (p <.05), doubled by day 1 (6.98 +/- 1.36 pg/mL, p <.05), remained elevated on day 3 (5.72 +/- 0.96 pg/mL, p <.05), and peak levels were related to chest radiograph extravascular lung water score (r(p) = 0.64, p =.003). CONCLUSIONS: Although the initial increase in plasma surfactant protein-A and -B may represent hydrostatic stress failure of the alveolocapillary barrier, the prolonged elevation, when hemodynamic abnormalities have resolved, and the delayed elevation of tumor necrosis factor-alpha are consistent with pulmonary parenchymal inflammation, which may further damage the alveolocapillary barrier. This prolonged physiologic defect at the alveolocapillary barrier after acute cardiogenic pulmonary edema may partly account for the vulnerability of these patients to recurrent pulmonary fluid accumulation.     

Inhaled nitric oxide reduces lung edema during fluid resuscitation in ovine acute lung injury

OBJECTIVE: Fluid resuscitation in sepsis-related lung injury is limited by aggravation of pulmonary edema. Hypovolemia, however, may compromise tissue perfusion and contribute to organ dysfunction. We hypothesized that inhaled nitric oxide would reduce edema formation during fluid therapy. DESIGN AND SETTING: Prospective laboratory investigation in a university research laboratory. PARTICIPANTS: Eighteen chronically instrumented sheep. INTERVENTIONS: The animals were randomly assigned to one of three groups and received endotoxin (S. typhi, 10 ng kg(-1) min(-1)) for 30 h. After 24 h the sheep were anesthetized (ketamine/midazolam), mechanically ventilated with oxygen, and received 0.1 ml kg(-1) oleic acid: oxy group (n=6), an infusion of Ringer's lactate was restricted to 1 ml kg(-1) h(-1); fluid/oxy group (n=6), a bolus of 10 ml kg(-1) Ringer's lactate plus 10 ml kg(-1) h(-1) was given; fluid/NO group (n=6), the sheep were treated as in the fluid/oxy group, except that they inhaled nitric oxide (20 ppm). MEASUREMENTS AND RESULTS: The extravascular lung water index was measured using thermodye dilution. Oleic acid increased extravascular lung water, impaired oxygenation, and reduced cardiac index at 26 h in all groups. After 30 h the extravascular lung water in the fluid/NO group was not higher than in the oxy group and significantly than in the fluid/oxy group. While cardiac index returned to the level of sepsis baseline in fluid/NO and fluid/oxy, it was reduced in the oxy group after 30 h. There were no significant differences in cardiac index between groups. CONCLUSIONS: Inhaled nitric oxide may be an option for reducing edema formation secondary to fluid resuscitation in acute lung injury.     

Effects of inhaled aerosolized iloprost and inhaled NO on pulmonary circulation and edema formation in ovine lung injury

Although inhaled NO (iNO) has been shown to lower pulmonary pressures and edema accumulation in experimental acute lung injury, its clinical use has been questioned because of a lack of improvement in outcome, rebound phenomena, and potential toxicity. We investigated the effects of aerosolized iloprost, a stable prostacyclin analogue, compared with iNO on pulmonary pressures and lung edema in 20 female sheep with oleic acid lung injury. The most effective dose of iloprost was determined in healthy animals before the experiment. Anesthetized and ventilated sheep received a central venous oleic acid infusion and were continuously infused with Ringer lactate to achieve a positive fluid balance (5 mL.kg(-1).h(-1)). In the iNO group (n = 6), iNO (20 ppm) was administered continuously for 8 h. Animals in the iloprost group (n = 6) received aerosolized iloprost (40 microg 2 h(-1)). Animals in the control group (n = 6) had no further intervention. Oleic acid infusion was associated with impaired oxygenation, pulmonary hypertension, and lung edema in all groups. Although iNO significantly decreased pulmonary vascular resistance index, effective pulmonary capillary pressure, and extravascular lung water index, these parameters were unaffected by iloprost. Oxygenation index (Pao2/Fio2) increased significantly both during NO and iloprost inhalation but also tended to improve in the control group over time. In contrast to iNO, the investigated dose of iloprost was ineffective to attenuate acute lung injury-induced changes in pulmonary hemodynamics and lung edema in this experimental model.     

Piretanide in chronic and acute decompensated heart failure. Effect on hemodynamics and vasoactive hormones

Eight patients with chronic heart failure classified as NYHA class II to III (group 1) and nine patients with acute decompensated heart failure classified as NYHA class IV (group 2) were treated with piretanide at a dosage of 12 mg administered intravenously. In both groups the level of prostaglandine PGE2 as well as plasma renine activity significantly increased prior to the onset of diuresis. The percentage increase was more pronounced in group 1 which had lower baseline values. With a time-lag, the norepinephrine plasma level also increased significantly. During the first 30 minutes there was only little effect on blood pressure, pulmonary artery pressure and cardiac output in patients with chronic heart failure (group 1). Only after 60 minutes there was a significant decrease in mean pulmonary artery pressure (from 39 +/- 17 to 33 +/- 18 mm Hg; p less than 0.05). In patients with acute decompensated heart failure (group 2) piretanide led to a significant reduction in mean pulmonary artery pressure (from 42 +/- 13 to 37 +/- 12 mm Hg; p less than 0.05) within 15 minutes after administration, i.e. even prior to the onset of diuresis. Thus, the administration of piretanide had a positive effect on hemodynamics in patients with chronic as well as in patients with acute decompensated heart failure. Significant improvement prior to diuresis onset, however, was only found in patients with acute decompensated heart failure. These effects may be explained by a stimulation of prostaglandines which promote vasodilation. They are increased by the diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Criteria for the safety of transfusion of colloidal solutions in patients with acute lung lesions

The prospective study explored the hemodynamic effects of colloidal solution replacement therapy and the criteria for its safety in patients with acute lung parenchymatous lesions (ALPL) attended by hypoalbuminemia and coagulopathy. There were 68 observations of the effects of colloidal solutions: 20% albumin solution (n=25), freshly frozen plasma (FFP) (n=20), 6% hydroxyethylated starch (HES) 130/0.4 9:1 (n=23). The colloidal solutions were infused at a constant rate; the infusion was stopped until pulmonary wedge pressure (PWP) was 25% greater than its baseline value. Before and after infusion, the parameters of central hemodynamics and oxygen transport, extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and colloid-osmotic pressure (COP) were measured. The infusion volumes were 3.8 +/- 0.4, 13.7 +/- 1.4, and 13.4 +/- 1.3 ml/kg for 20% albumin solution, 6% HES 130/0.4, and FFP, respectively. The PWP-COP gradient increased in all groups. After FFP infusion, there was an increase in ELWI and lung shunt. After 20% albumin solution, there was a delayed increase in ELWI. There was no rise in ELWI after 6% HES administration. In the 20% albumin solution group, the increased ELWI was recorded in patients who had positive baseline PWP-COP gradients (p < 0.05). A combination of higher PVPI and a positive PWP-COP value causes a greater increase in ELWI after 20% albumin solution infusion than in the normal PVPI group. In patients with ALPL, FFP infusion may lead to an increase in the accumulation of extravascular lung water. A negative preinfusion PWP-COP gradient is a safety criterion for the infusion of 20% albumin solution in patients with ALPL. The increased PVPI in combination with a positive PWP-COP gradient is an aggravating factor.     

Accuracy of the double indicator method for measurement of extravascular lung water depends on the type of acute lung injury

OBJECTIVE: The double indicator method is sensitive to alterations in the distribution of pulmonary blood flow. This distribution is influenced by the type of lung injury. The aim of this study was to compare measurements of lung water by the double indicator method with measurements obtained by gravimetry in a direct lung injury model induced by tracheal instillation of hydrochloric acid and in an indirect lung injury model induced by the intravenous injection of oleic acid. DESIGN: Prospective, randomized laboratory study. SETTING: Animal research laboratory. SUBJECTS: Forty-two female pigs (28+/-3 kg). INTERVENTIONS: Pigs were anesthetized and ventilated and were allocated into three groups: control (n = 6), hydrochloric acid (4 mL/kg intratracheally, n = 24), or oleic acid (0.1 mL/kg intravenously, n = 12). MEASUREMENTS AND MAIN RESULTS: Hydrochloric acid instillation or oleic acid injection resulted in a similar hypoxemia and induced a two- to three-fold increase in extravascular lung water (EVLW) by gravimetry (EVLWG) at 3 hrs compared with controls. In the oleic acid group, there was a significant correlation between EVLWG and EVLW by double indicator method (EVLWDI; r =.88, p <.0001). The bias for EVLWDI - EVLWG measurements was -5.2 mL/kg (95% confidence interval, -5.7 to -4.7 mL/kg) with 95% limits of agreement of -7 to -3.4 mL/kg. In the hydrochloric acid group, there was no significant correlation between EVLWDI and EVLWG values, and the double indicator method failed to detect pulmonary edema in 65% of the animals (EVLWDI <8 mL/kg). The bias was -7.9 mL/kg (95% confidence interval, -9.3 to -6.5 mL/kg) with 95% limits of agreement of -14.4 to -1.4 mL/kg. CONCLUSIONS: The double indicator method is useful for evaluation of pulmonary edema in indirect lung injury, as induced by oleic acid, but produces misleading values in direct lung injury, as produced by hydrochloric instillation.     

Tezosentan counteracts endotoxin-induced pulmonary edema and improves gas exchange

Sepsis-induced acute lung injury is still associated with high morbidity and mortality. The pathophysiology is complex, and markers of injury include increased extravascular lung water. To evaluate the effects of the novel dual endothelin receptor antagonist tezosentan on endotoxin-induced changes in extravascular lung water and gas exchange, 16 pigs were anaesthetized and catheterized. Twelve animals were subjected to 5 h of endotoxemia. After 2 h, six of these animals received a bolus of tezosentan 1 mg kg(-1) followed by a continuous infusion of 1 mg kg(-1) h(-1) to the end of the experiment at 5 h. Conventional pulmonary and hemodynamic parameters were measured. Extravascular lung water was determined in these pigs after 5 h of endotoxemia, as well as in the four additional nonendotoxemic sham animals. Tezosentan in the current dosage counteracted the deterioration of lung function caused by endotoxin, as measured by dead space, venous admixture, and compliance. In addition, pulmonary hypertension was attenuated. Tezosentan had a marked effect on the endotoxin-induced increase in extravascular lung water that was reduced to levels observed in nonendotoxemic sham animals. These results suggest that endothelin is involved in endotoxin-induced lung injury and the development of pulmonary edema. Dual endothelin receptor antagonism may be of value in the treatment of sepsis-related acute lung injury.