Mechanical ventilation may increase susceptibility to the development of bacteremia

OBJECTIVE: We examined the hypothesis that mechanical ventilation with a potentially injurious strategy would predispose animals to the detrimental effects of subsequent instillation of bacteria. DESIGN: Interventional animal study. SETTING: A university hospital research laboratory. SUBJECTS: Fifty Sprague-Dawley male rats. INTERVENTIONS: Rats were anesthetized and randomized to receive a protective (tidal volume 7 mL/kg, positive end-expiratory pressure 5 cm H(2)O, n = 25) or an injurious ventilatory strategy (tidal volume 21 mL/kg, zero positive end-expiratory pressure, n = 25). Hemodynamics were similar during the 1-hr ventilation period in the two groups. Animals were then disconnected from the ventilator and Pseudomonas aeruginosa was instilled intratracheally before extubation. Thereafter, animals breathed spontaneously; mortality rate was assessed up to 48 hrs, at which time the animals were killed. MEASUREMENTS AND MAIN RESULTS: The 48-hr mortality rate was 28% in the protective group and 40% in the injurious group (p = not significant). A positive bacterial culture from the lung was obtained in 56% of the surviving rats in the low tidal volume group and 67% in the high tidal volume group (p =.059). A positive blood bacterial culture was found in 11% of the low tidal volume group and 33% in the high tidal volume group (p <.05). The absolute bacterial count in the blood was lower in the low tidal volume group compared with the high tidal volume group (p <.05). Concentrations of blood tumor necrosis factor-alpha and macrophage inflammatory protein-2, and lung macrophage inflammatory protein-2 at 48 hrs were significantly higher in the low tidal volume group than in the high tidal volume group. CONCLUSIONS: An injurious ventilatory strategy predisposes animals to subsequent bacteremia associated with an impaired host defense reflected by cytokine response.     

Protective effects of low tidal volume ventilation in a rabbit model of Pseudomonas aeruginosa-induced acute lung injury

OBJECTIVE: To determine whether low "stretch" mechanical ventilation protects animals from clinical sepsis after direct acute lung injury with Pseudomonas aeruginosa as compared with high "stretch" ventilation. DESIGN: Prospective study. SETTING: Experimental animal laboratory. SUBJECTS: Twenty-seven anesthetized and paralyzed rabbits. INTERVENTIONS: P. aeruginosa (109 colony forming units) was instilled into the right lungs of rabbits that were then ventilated at a tidal volume of either 15 mL/kg (n = 11) or 6 mL/kg (n = 7) for 8 hrs. Control animals were ventilated at a tidal volume of either 15 mL/kg (n = 4) or 6 mL/kg (n = 5) for 8 hrs, but an instillate without bacteria was used. A positive end-expiratory pressure of 3-5 cm H2O was used for all experiments. Radiolabeled albumin was used as a marker of alveolar epithelial permeability. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, arterial blood gas determination, alveolar permeability, wet-to-dry ratios on lungs, and time course of bacteremia were determined. When final values were compared with the values at the beginning of the experiment, there were significant decreases in mean arterial pressure (from 104 +/- 15 to 57 +/- 20 mm Hg), pH (from 7.46 +/- 0.04 to 7.24 +/- 15), Pao2 (from 528 +/- 35 to 129 +/- 104 torr [70.4 +/- 4.7 to 17.2 +/- 13.9 kPa]), and temperature (from 38.2 +/- 1 to 36.2 +/- 1.2 degrees C) in the high tidal volume group, whereas no significant differences were found in the low tidal volume group. Decreased alveolar permeability was shown in the low tidal volume group, as was decreased extravascular lung water in the uninstilled lung in the low tidal volume group (12.7 +/- 2.5 vs. 4.3 +/- 0.45 g H2O/g dry lung). No noteworthy difference was noted in the time course of bacteremia, although there was a trend toward earlier bacteremia in the high tidal volume group. CONCLUSIONS: In our animal model of P. aeruginosa-induced acute lung injury, low tidal volume ventilation was correlated with improved oxygenation, hemodynamic status, and acid-base status as well as decreased alveolar permeability and contralateral extravascular lung water.     

Pumpless extracorporeal lung assist for protective mechanical ventilation in experimental lung injury

OBJECTIVE: To test the hypothesis that ventilation with 3 mL/kg tidal volume combined with extracorporeal CO2 removal by arteriovenous interventional lung assist reduces ventilator-associated organ injury in experimental acute lung injury when compared with ventilation with 6 mL/kg tidal volume without interventional lung assist. DESIGN: Prospective, randomized, controlled trial. SETTING: A university research laboratory. SUBJECTS: A total of 14 pigs weighing 46 +/- 4 kg (mean +/- sd). INTERVENTIONS: Acute lung injury was induced by repeated lung lavages until Pao2 was <100 mm Hg, with Fio2 of 1.0 and positive end-expiratory pressure of 5 cm H2O, for 1 hr without additional lavages. Animals were randomized to an interventional group with a tidal volume of 3 mL/kg with interventional lung assist (n = 7) or to a control group with a tidal volume of 6 mL/kg without interventional lung assist (n = 7) for 24 hrs. Organ function in vivo was determined by laboratory analyses, including calculations of pulmonary ventilation/perfusion distribution. Histologic assessment of organ injury was performed post mortem after 24 hrs. MEASUREMENTS AND MAIN RESULTS: In both groups, gas exchange improved in the course of the study (p < .05). However, in contrast to control animals, animals with lower tidal volumes and interventional lung assist had severe ventilation/perfusion mismatch, as indicated by increased perfusion to lung areas with a low ventilation/perfusion ratio (p < .05). Other variables of organ function in vivo and results of histologic examination post mortem did not reveal any statistical difference between groups. CONCLUSIONS: Combined ventilation with lower tidal volumes and extracorporeal CO2 removal as compared with traditional low tidal volumes without extracorporeal CO2 removal is not associated with differences in organ injury. Obviously, ventilation with tidal volumes of <6 mL/kg may cause pulmonary de-recruitment when positive end-expiratory pressure is not adequately increased.     

Assessment of current methods quantitating extravascular lung water and pulmonary aeration in inhomogeneous lung injury: an experimental study

BACKGROUND: Single transpulmonary thermodilution (STTD) is a widely recognized technique for the quantification of extravascular lung water (EVLW). However, the accuracy of STTD can be substantially reduced in acute lung lesion (ALL) characterized by inhomogeneous distribution of edematous zones and major ventilation-perfusion mismatch. Quantitative computed tomography (CT) may be a helpful clinical adjunct allowing an assessment of pulmonary gas and tissue content. The purpose of the study was to compare the tissue volume index, as estimated by spiral CT (TVICT), with EVLW indices determined with STTD (EVLWISTTD), thermal-dye dilution (EVLWITDD), and postmortem gravimetry (EVLWIG) before and after oleic acid-induced ALL in sheep. MATERIALS: Eleven yearling sheep were randomly assigned to either an oleic acid (OA) group receiving an infusion of OA in a dose of 0.08 ml/kg i.v. or to a control group. The day before and immediately after the experiment, sheep underwent CT examinations. Pulmonary and systemic hemodynamics, oxygenation, EVLWISTTD and EVLWITDD were recorded. Linear regression analysis was used to assess the relationships between EVLWISTTD, EVLWITDD, EVLWIG, and TVICT (syngo PulmpCT, Siemens, Germany). RESULTS: OA caused 5- and 7-fold increments in poorly and nonaerated lung volumes, respectively, and increased total lung volume and TVICT, EVLWISTTD, EVLWITDD, and TVICT demonstrated a close agreement with EVLWIG (r = 0.86, 0.90, and 0.97, respectively; p < 0.001). TVICT overestimated reference EVLWIG values to the greatest extent. CONCLUSION: In a sheep model of OA-induced ALL, pulmonary tissue volume as estimated by quantitative CT closely correlates with EVLWI measured by dilutional methods and postmortem gravimetry.     

Massive brain injury enhances lung damage in an isolated lung model of ventilator-induced lung injury

OBJECTIVE: To assess the influence of massive brain injury on pulmonary susceptibility to injury attending subsequent mechanical or ischemia/reperfusion stress. DESIGN: Prospective experimental study. SETTING: Animal research laboratory. SUBJECTS: Twenty-four anesthetized New Zealand White rabbits randomized to control (n = 12) or induced brain injury (n = 12) group. INTERVENTIONS: After randomization, brain injury was induced by inflation of an intracranial balloon-tipped catheter, and animals were ventilated with a tidal volume of 10 mL/kg and zero end-expiratory pressure for 120 mins. Following heart-lung block extraction, isolated and perfused lungs were subjected to injurious ventilation with peak airway pressure 30 cm H2O and positive end-expiratory pressure 5 cm H2O for 30 mins. MEASUREMENTS AND MAIN RESULTS: No difference was observed between groups in gas exchange, lung mechanics, or hemodynamics during the 2-hr in vivo period following induction of brain injury. However, after 30 mins of ex vivo injurious mechanical ventilation, lungs from the brain injury group showed greater change in ultrafiltration coefficient, weight gain, and alveolar hemorrhage (all p < .05). CONCLUSIONS: Massive brain injury might increase lung vulnerability to subsequent injurious mechanical or ischemia-reperfusion insults, thereby increasing the risk of clinical posttransplant graft failure.     

肺复张后不同潮气量对急性肺损伤大鼠肺血管内皮舒张功能的影响

目的 观察肺复张与肺复张后不同潮气量对ALI大鼠肺内皮舒张功能的影响.方法 内毒素(LPS)静脉注射复制大鼠ALI模型.25只清洁级SD大鼠随机(随机数字法)分成5组,每组5只:对照组、ALI组、小潮气量(VT)组(LV组,VT 6 mL/kg)、SI+小VT组(SI+LV组,VT 6 mL/kg)、SI+常规VT组(SI+MV组,VT12mL/kg),SI(30 cmH2O)维持30 s,进行肺复张.应用不同潮气量联合肺复张监测呼吸功能和血流动力学,实验5 h后放血处死动物.观察肺组织病理形态改变和湿/干重比(W/D);放射免疫法检测肺组织中ET-1;免疫组织化学法半定量分析肺动脉内皮细胞内皮型一氧化氮合酶(eNOS)蛋白表达水平;血管张力实验检测离体肺动脉环对乙酰胆碱(Ach)和硝普钠(SNP)介导的舒张功能的影响;ELISA检测肿瘤坏死因子-α(TNF-α)炎症反应指标.结果 与CON组比较,LPS增加各组内肺水肿,加重肺损伤,增加TNF-α含量,增加ET-1含量,减少肺动脉内皮细胞eNOS蛋白表达,减弱Ach介导的内皮依赖的舒张功能,最终影响内皮功能.SI+LV组ET-1含量为(109.18±15.62)pg/mL,SI+MV组和LV组肺组织ET-1含量分别为(158.78±30.40)pg/mL和(152.35±8.21)pr/mL,较SI+LV组升高(P＜0.05);SI+LV组肺组织eNOS蛋白表达的iOD值为(12663.83±1348.93),SI+MV组和LV组肺组织eNOS蛋白表达的iOD值分别为(9208.12±2773.68)和(9339.53±3366.40),较SI+LV组无统计学差异,但有降低趋势(P＞0.05);与SI+LV组比较,ALI组和SI+MV组在不同浓度Ach作用下内皮依赖的舒张功能降低(P＜0.05),LV组虽然与SI+LV组比较差异无统计学意义,但Ach介导舒张功能有下降的趋势;SI+LV组肺组织TNF-α含量(2374.53±410.60)ng/L,较SI+MV组(3468.86±659.25)ng/L和LV组(3370.75±314.17)ng/L降低(P＜0.05).结论 肺复张联合大潮气量和小潮气量机械通气能够改善ALI大鼠肺血管内皮舒张功能,肺复张联合小潮气量可进一步减轻ALI大鼠肺血管内皮舒张功能的损伤.     

Pulmonary surfactant is altered during mechanical ventilation of isolated rat lung

OBJECTIVE: To test the hypothesis that the lung injury induced by certain mechanical ventilation strategies is associated with changes in the pulmonary surfactant system. DESIGN: Analysis of the pulmonary surfactant system from isolated rat lungs after one of four different ventilatory strategies. SETTING: A research laboratory at a university. SUBJECTS: A total of 45 Sprague-Dawley rats. INTERVENTIONS: Isolated lungs were randomized to either no ventilation (0-TIME) or to ventilation at 40 breaths/min in a humidified 37 degrees C chamber for either 30 mins or 120 mins with one of the following four strategies: a) control (CON, 7 mL/kg, 3 cm H2O positive end-expiratory pressure); b) medium volume, zero end-expiratory pressure (MVZP, 15 mL/kg, 0 cm H2O end-expiratory pressure); c) medium volume, high positive end-expiratory pressure (MVHP, 15 mL/kg, 9 cm H2O positive end-expiratory pressure); and d) high volume, zero end-expiratory pressure (HVZP, 40 mL/kg, 0 cm H2O end-expiratory pressure). MEASUREMENTS: Pressure-volume curves were determined before and after the ventilation period, after which the lungs were lavaged for surfactant analysis. MAIN RESULTS: Compared with 0-TIME, 30 mins of ventilation with the HVZP strategy or 120 mins of ventilation with CON and MVZP strategies caused a significant decrease in compliance. Groups showing a decreased compliance had significant increases in the amount of surfactant, surfactant large aggregates, and total lavage protein compared with 0-TIME. CONCLUSIONS: A short period of injurious mechanical ventilation can cause a decrease in lung compliance that is associated with a large influx of proteins into the alveolar space and with alterations of the pulmonary surfactant system. The changes of surfactant in these experiments are different from those seen in acute lung injury, indicating that they may represent an initial response to mechanical ventilation.     

Effect of post recruitment maneuver ventilation by different tidal volume on lung vascular endothelial diastole function in rats with acute lung injury

BACKGROUND: This study aimed to observe the effect of recruitment maneuver (RM) and post-RM ventilation at different tidal volume on lung vascular diastole endothelial function in rats with acute lung injury (ALI).METHODS: A ALI rat model was produced by intravenous infusion of lipopolysaccharide (6 mg/kg). Twenty-five rats were randomly divided into five groups: control group (n=5), ALI group (n=5), low tidal volume group (LV group, VT 6 mL/kg, n=5), sustained inflation (SI) with low tidal volume group (SI+LV group, VT 6 mL/kg, n=5), and SI with moderate tidal volume group (SI+MV group, VT 12 mL/kg, n=5). RM was performed with SI, airway pressure 30 cmH₂O for 30 seconds, and positive end-expiratory pressure (PEEP) was set to 5 cmH₂O. Lung tissue was taken after 5 hours of mechanical ventilation. Mean arterial blood pressure (MAP) was monitored during the experiment. Endothelin-1 (ET-1), endothelial nitricoxide synthase (eNOS), Ach-induced endothelium-dependent relaxation response of isolated pulmonary artery rings were determined at 5 hours.RESULTS: LPS increased ET-1 level, decreased the expression of eNOS in lung tissue, impaired the Ach-induced endothelium-dependent relaxation response in the pulmonary artery, without obvious effect on systemic hemodynamics. SI+LV significantly reduced LPS-induced elevation of ET-1 level, increased the expression of eNOS, significantly improved endothelial dysfunction, and improved the dysfunction of endothelium-dependent relaxation in the pulmonary artery.CONCLUSIONS: RM with a high or low tidal volume ventilation could improve the lung vascular endothelial function of rats with acute lung injury, and RM with low tidal volume ventilation could lower significantly the injury of lung vascular endothelial diastole function in rats with acute lung injury.     

Augmented lung injury due to interaction between hyperoxia and mechanical ventilation

OBJECTIVE: Mechanical overdistension and hyperoxia can independently cause lung injury, yet little is known about their combined effects. We hypothesized that hyperoxia exacerbates lung injury caused by large tidal volume ventilation. DESIGN: Experimental study. SETTING: University laboratory. SUBJECTS: Anesthetized, paralyzed rabbits. INTERVENTIONS: In experiment 1, 12 rabbits were ventilated with 25 mL/kg tidal volumes at positive end-expiratory pressure of 0 cm H2O for 4 hrs with either hyperoxia (HO; FiO2 = 0.5) or normoxia (NO; FiO2 = 0.21). In experiment 2, a separate group of animals were randomized to one of four groups to assess the interaction of tidal volume and inspired oxygen concentration on potential mediators of injury after 2 hrs of ventilation, before significant injury occurs: a) NO+normal tidal volume (NV; VT = 10 mL/kg); b) HO+NV; c) NO+high tidal volume (HV; VT = 25 mL/kg); d) HO+HV (n = 3 per group). MEASUREMENTS AND MAIN RESULTS:: In the first study, HO compared with the NO group had significantly reduced PaO2/FiO2 ratio (320 +/- 110 vs. 498 +/- 98, p = .014) and increased lung injury scores at 4 hrs. Hyperoxia also significantly increased polymorphonuclear leukocytes, growth-related oncogene-alpha (2073 +/- 535 vs. 463 +/- 236 pg/mL, p = .02), and monocyte chemotactic protein-1 (7517 +/- 1612 vs. 2983 +/- 1289 pg/mL, p = .05) concentrations in bronchoalveolar lavage fluid. The second study showed increased alveolar-capillary permeability to a 70-kD fluorescent-labeled dextran only in response to the combination of both HO and HV. Chemokines and bronchoalveolar lavage fluid neutrophils were elevated in both HV groups; however, hyperoxia did not further increase chemokine or neutrophil counts over normoxia. No difference in lipid peroxidation was seen between groups. CONCLUSIONS: Moderate hyperoxia exacerbates lung injury in a large tidal volume model of ventilator-induced lung injury. The mechanism by which this occurs is not mediated by increased production of CXC chemokines or lipid peroxidation.     

Extravascular lung water determined with single transpulmonary thermodilution correlates with the severity of sepsis-induced acute lung injury

OBJECTIVE: To find out if the extravascular lung water index (EVLWI) and the derived permeability indexes determined by the single transpulmonary thermodilution technique are associated with markers of acute lung injury in human septic shock. DESIGN: Prospective, observational study. SETTING: Mixed intensive care unit of a 900-bed university hospital. PATIENTS: Thirty-eight consecutive adult patients with septic shock and acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The variables were assessed over a 72-hr period and included hemodynamics, EVLWI, and pulmonary vascular permeability indexes determined with the single indicator transpulmonary thermodilution technique, lung compliance, oxygenation ratio (Pao2/Fio2), lung injury score, cell counts, and the plasma concentration of endothelin-1. At day 1, EVLWI was elevated (>or=7 mL/kg) in 28 (74%) patients and correlated with lung compliance (r=-.48, p=.002), Pao2/Fio2 (r=-.50, p=.001), lung injury score (r=.46, p=.004), roentgenogram quadrants (r=.39, p=.02), and platelet count (r=-.43, p=.007). At day 3, EVLWI correlated with compliance (r=-.51, p=.002), Pao2/Fio2 (r=-.49, p = .006), and lung injury score (r=.53, p=.003). At day 3, EVLWI and pulmonary vascular permeability indexes were higher in nonsurvivors (p<.05). The plasma concentration of endothelin-1 (mean+/-sd) was significantly higher in patients with elevated EVLWI (>or=7 mL/kg) (3.85+/-1.40 vs. 2.07+/-0.38 pg/mL, respectively). Twenty-two (59%) patients died before day 28. CONCLUSIONS: In human septic shock, EVLWI demonstrated moderate correlation with markers of acute lung injury, such as lung compliance, oxygenation ratio, roentgenogram quadrants, and lung injury score. In nonsurvivors, EVLWI and permeability indexes were significantly increased at day 3. Thus, EVLWI might be of value as an indicator of prognosis and severity of sepsis-induced acute lung injury.     

Recombinant human activated protein C ameliorates oleic acid-induced lung injury in awake sheep

Introduction

Acute lung injury (ALI) may arise both after sepsis and non-septic inflammatory conditions and is often associated with the release of fatty acids, including oleic acid (OA). Infusion of OA has been used extensively to mimic ALI. Recent research has revealed that intravenously administered recombinant human activated protein C (rhAPC) is able to counteract ALI. Our aim was to find out whether rhAPC dampens OA-induced ALI in sheep.

Methods

Twenty-two yearling sheep underwent instrumentation. After 2 days of recovery, animals were randomly assigned to one of three groups: (a) an OA+rhAPC group (n = 8) receiving OA 0.06 mL/kg infused over the course of 30 minutes in parallel with an intravenous infusion of rhAPC 24 mg/kg per hour over the course of 2 hours, (b) an OA group (n = 8) receiving OA as above, or (c) a sham-operated group (n = 6). After 2 hours, sheep were sacrificed. Hemodynamics was assessed by catheters in the pulmonary artery and the aorta, and extravascular lung water index (EVLWI) was determined with the single transpulmonary thermodilution technique. Gas exchange was evaluated at baseline and at cessation of the experiment. Data were analyzed by analysis of variance; a P value of less than 0.05 was regarded as statistically significant.

Results

OA induced profound hypoxemia, increased right atrial and pulmonary artery pressures and EVLWI markedly, and decreased cardiac index. rhAPC counteracted the OA-induced changes in EVLWI and arterial oxygenation and reduced the OA-induced increments in right atrial and pulmonary artery pressures.

Conclusions

In ovine OA-induced lung injury, rhAPC dampens the increase in pulmonary artery pressure and counteracts the development of lung edema and the derangement of arterial oxygenation.     

Update in ARDS management: recent randomized controlled trials that changed our practice

In the last 7 years, 14 randomized controlled trials in patients with acute respiratory distress syndrome (ARDS) have shown that: Mechanical ventilation with a tidal volume of 6 mL/kg of predicted body weight is better than mechanical ventilation with a tidal volume of 12 mL/kg of predicted body weight. Prone positioning improves oxygenation but poses safety concerns. A high level of positive end-expiratory pressure does not improve survival. High-frequency oscillatory ventilation is in theory the ideal "lung-protective" method, but its benefits have not been proven. No drug therapy has been shown to improve survival in patients with ARDS. Exogenous surfactant may improve oxygenation but has no significant effect on the death rate or length of use of mechanical ventilation. Low-dose inhaled nitric oxide has no substantial impact on the duration of ventilatory support or on the death rate. Partial liquid ventilation may be beneficial in young patients with acute lung injury or ARDS, although further study is needed to confirm this.     

Effects of cyclic opening and closing at low- and high-volume ventilation on bronchoalveolar lavage cytokines

OBJECTIVE: To examine the mechanisms of ventilator-induced lung injury at low and high lung volumes. DESIGN: Prospective, randomized, laboratory study. SETTING: University research laboratory. SUBJECTS: Eighty-eight adult male Sprague-Dawley rats. INTERVENTIONS: Mechanical ventilation using low and high lung volumes. MEASUREMENTS AND MAIN RESULTS: An ex vivo rat lung model was used. In study I (ventilation at low lung volumes), rat lungs (n = 40) were randomly assigned to various modes of ventilation: a) opening and closing with positive end-expiratory pressure (PEEP; control): tidal volume 7 mL/kg and PEEP 5 cm H2O; b) opening and closing from zero end-expiratory pressure (ZEEP): tidal volume 7 mL/kg and PEEP 0; or c) atelectasis. Peak inspiratory pressure was monitored at the beginning and end of 3 hrs of ventilation. At the end of 3 hrs of ventilation, the lungs were lavaged, and the concentrations of tumor necrosis factor-alpha, macrophage inflammatory protein-2, and interleukin-6 cytokines were measured in the lavage. In study II (ventilation at high volumes), rat lungs (n = 45) were randomly assigned to a) cyclic lung stretch: pressure-controlled ventilation, peak inspiratory pressure 50 cm H2O, and PEEP 8 cm H2O; b) continuous positive airway pressure at 50 cm H2O (CPAP50); or c) CPAP at the mean airway pressure of the cyclic stretch group (CPAP 31 cm H2O). Bronchoalveolar lavage cytokine concentrations (tumor necrosis factor-alpha, macrophage inflammatory protein-2, and interleukin-6) were measured at the end of 3 hrs of ventilation. In the low volume study, there was no difference in bronchoalveolar lavage cytokine concentrations between the PEEP group and the atelectatic group. All cytokines were significantly higher in the ZEEP group compared with the atelectasis group. Macrophage inflammatory protein-2 was significantly higher in the ZEEP group compared with the PEEP group. Lung compliance, as reflected by change in peak inspiratory pressure, was also significantly worse in the ZEEP compared with the PEEP group. In the high-volume study, tumor necrosis factor-alpha and interleukin-6 were significantly higher in the cyclic stretch group compared with the CPAP 31 group. There was no significant difference between the cytokine concentrations in the cyclic stretch group compared with the CPAP 50 group. CONCLUSION: We conclude that at low lung volumes, cyclic opening and closing from ZEEP leads to greater increases in bronchoalveolar lavage cytokines than atelectasis. With high-volume ventilation, over time, the degree of overdistension is more associated with increases in bronchoalveolar lavage cytokines than cyclic opening and closing alone.     

Host response to intratracheally instilled bacteria in ventilated and nonventilated rats

OBJECTIVE: Pneumonia occurs in approximately 7% of hospitalized patients. Susceptibility to certain bacteria such as Pseudomonas aeruginosa increases in critically ill patients, particularly those requiring mechanical ventilation. Previous studies investigating this susceptibility have used injurious modes of ventilation. The objective of this study was to evaluate the host's response to intratracheal instillation of P. aeruginosa in the setting of noninjurious mechanical ventilation and compare this with normal, spontaneously breathing animals receiving bacteria. DESIGN: Randomized, controlled in vivo animal study. SETTING: Research laboratory at a university-affiliated institution. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Rats were randomized into four groups: spontaneously breathing given saline, spontaneously breathing given bacteria, mechanically ventilated given saline, and mechanically ventilated given bacteria. The ventilation strategy used involved low stretch (tidal volume of 8 mL/kg) with a positive end-expiratory pressure of 5 cm H2O. MEASUREMENTS AND MAIN RESULTS: Lung compliance, bacterial recovery, surfactant, total cells, and cytokine concentrations in the lung lavage were analyzed after 4 hrs. Results showed that neither ventilation nor bacteria alone altered lung function, although the combination of ventilation and Pseudomonas significantly decreased arterial oxygenation and lung compliance. Increases in lavage cell counts, cytokines, and surfactant were observed in both groups administered bacteria compared with animals given saline. However, there were no significant differences in bacterial recovery, cell counts, cytokines, and surfactant measurements in the groups given bacteria. CONCLUSIONS: These data suggest that bacterial instillation with low-stretch ventilation had a significant effect on lung function but did not alter the inflammatory response to a bacterial challenge over this time course compared with spontaneously breathing animals.     

Positive end-expiratory pressure above lower inflection point minimizes influx of activated neutrophils into lung

OBJECTIVES: To compare the effects of low vs. high tidal volume (Vt) with three positive end-expiratory pressure (PEEP) strategies on activated neutrophil influx into the lung. DESIGN: Prospective, randomized controlled animal study. SETTING: Animal laboratory in a university hospital. SUBJECTS: Newborn piglets. INTERVENTIONS: Surfactant-depleted piglets were randomized in littermate pairs; to PEEP of either 0 (zero end-expiratory pressure [ZEEP]; n = 6), 8 cm H2O (PEEP 8; n = 5), or 1 cm H2O above the lower inflection point (LIP) (PEEP>LIP; n = 6). Within each pair piglets were randomized to a low VT (5-7 mL/kg) or high VT strategy (17-19 mL/kg). After 4 hrs of mechanical ventilation, 18-fluorodeoxyglucose (18FDG) was injected and positron emission tomography scanning was performed. MEASUREMENTS AND MAIN RESULTS: VT and PEEP changes on influx constants of 18FDG were assessed by analysis of variance. A within-litter comparison of Vt was nonsignificant (p = .50). A between-litter comparison, ordered in linear trend rank, from ZEEP, to PEEP 8, to PEEP>LIP, showed a strong effect of PEEP on influx constant (p = .019). CONCLUSIONS: PEEP set above the LIP on the inspiratory limb of the pressure-volume curve affords a stronger lung protection than VT strategy.     

The open lung during small tidal volume ventilation: concepts of recruitment and "optimal" positive end-expiratory pressure.

OBJECTIVES: To test the hypotheses that during small tidal volume ventilation (5 mL/kg) deliberate volume recruitment maneuvers allow expansion of atelectatic lung units and that a high positive end-expiratory pressure (PEEP) above the lower inflection point of the pressure/volume (PV) curve is not necessarily required to maintain recruited lung volume in acute lung injury. DESIGN: Prospective, randomized, controlled animal study. SETTING: An animal laboratory in a university setting. SUBJECTS: Adult New-Zealand rabbits. INTERVENTIONS: We studied a) the relationship of dynamic loops during intermittent positive pressure ventilation to the quasi-static PV curve, and b) the effect of lung recruitment on oxygenation, end-expiratory lung volume (EELV), and dynamic compliance in two groups (n = 4 per group) of lung-injured animals (lung lavage model): 1) the sustained inflation group, which received ventilation after a recruitment maneuver (sustained inflation); and 2) the control group, which received ventilation without any lung recruitment. MEASUREMENTS AND MAIN RESULTS: In the presence of PV hysteresis, a single sustained inflation to 30 cm H2O boosted the ventilatory cycle onto the deflation limb of the PV curve. This resulted in a significant increase in EELV, oxygenation, and dynamic compliance despite equal PEEP levels used before and after the recruitment maneuver. Furthermore, after a single sustained inflation, oxygenation remained high over 4 hrs of ventilation when a PEEP above the critical closing pressure of the lungs, defined as "optimal" PEEP, was used and was significantly higher compared with that in the control group ventilated at equal PEEP without preceding lung recruitment. CONCLUSIONS: The observation that ventilation occurs on the deflation limb of the tidal cycle-specific PV curve allows placement of the ventilatory cycle, by means of a recruitment maneuver, onto the deflation limb of the PV envelope of the optimally recruited lung. This strategy ensures sufficient lung volume recruitment to maintain the lungs during the tidal cycle while using relatively low airway pressures.     

Tidal volume increases do not affect alveolar mechanics in normal lung but cause alveolar overdistension and exacerbate alveolar instability after surfactant deactivation

OBJECTIVE: We utilized microscopy to measure the impact of increasing tidal volume on individual alveolar mechanics (i.e., the dynamic change in alveolar size during tidal ventilation) in the living porcine lung. DESIGN: In three anesthetized, mechanically ventilated pigs, we observed normal alveoli (n = 27) and alveoli after surfactant deactivation by Tween 20 lavage (n = 26) at three different tidal volumes (6, 12, and 15 mL/kg). Alveolar area was measured at peak inspiration (I) and at end expiration (E) by image analysis and I minus E was calculated as an index of alveolar stability (I-Edelta). MEASUREMENTS AND MAIN RESULTS: In normal alveoli, increasing tidal volume did not change alveolar area at I (6 mL/kg = 9726 +/- 848 microm; 15 mL/kg = 9,637 +/- 884 microm ), E (6 mL/kg = 9747 +/- 800 microm; 15 mL/kg = 9742 +/- 853 microm ), or I-Edelta (6 mL/kg = -21 +/- 240 microm; 15 mL/kg = -105 +/- 229 microm ). In contrast, with surfactant deactivation, increasing tidal volume significantly increased alveolar area at I (6 mL/kg = 11,413 +/- 1032 microm; 15 mL/kg = 13,917 +/- 1214 microm ), at E (6 mL/kg = 10,462 +/- 906 microm; 15 mL/kg = 12,000 +/- 1066 microm ), and I-Edelta (6 mL/kg = 825 +/- 276 microm; 15 mL/kg = 1917 +/- 363 microm ). Moreover, alveolar instability (increased I-Edelta) was significantly increased at all tidal volumes with altered surface tension when compared with normal alveoli. CONCLUSIONS: We conclude that high tidal volume ventilation does not alter alveolar mechanics in the normal lung; however, in the surfactant-deactivated lung, it causes alveolar overdistension and exacerbates alveolar instability.     

Factors influencing the estimation of extravascular lung water by transpulmonary thermodilution in critically ill patients

OBJECTIVE: To investigate factors that may influence the estimation of extravascular lung water (EVLW) with a single (cold) indicator compared with assessment using two indicators (thermo-dye dilution). DESIGN: Post hoc analysis of an electronic hemodynamic database. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Forty-eight critically ill patients monitored by the thermo-dye dilution technique in the postoperative period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The EVLW was simultaneously assessed by the thermo-dye dilution technique (EVLWref) and estimated by transpulmonary thermodilution (EVLWest). EVLWref index ranged between 1 and 40 mL/kg (mean 10 +/- 7 mL/kg) and EVLWest between 2 and 39 mL/kg (mean 9 +/- 6 mL/kg). EVLWref was closely correlated (r = .96) with EVLWest. The mean difference (bias) between EVLWref and EVLWest was -0.5 +/- 1.9 mL/kg. The bias was not influenced by the weight, height, body surface area, body mass index, Pao2, intrathoracic blood volume, cardiac output, or dosage of vasoactive agents. In contrast, the bias was slightly but significantly influenced by EVLWref, Pao2/Fio2 ratio, tidal volume, and level of positive end-expiratory pressure. CONCLUSIONS: In our surgical intensive care unit population, the estimation of EVLW by transpulmonary thermodilution was influenced by the amount of EVLW, the Pao2/Fio2 ratio, the tidal volume, and the level of positive end-expiratory pressure. However, compared with the double indicator method, transpulmonary thermodilution estimation remained clinically acceptable even in patients with severe lung disease.     

Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients.

OBJECTIVE: To assess the safety and potential efficacy of a mechanical ventilation strategy designed to reduce stretch-induced lung injury in acute respiratory distress syndrome. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: Eight intensive care units in four teaching hospitals. PATIENTS: Fifty-two patients with acute respiratory distress syndrome. INTERVENTIONS: Traditional tidal volume patients: tidal volume 10-12 mL/kg ideal body weight, reduced if inspiratory plateau pressure was > 55 cm H2O (7.3 kPa). Small tidal volume patients: tidal volume 5-8 mL/kg ideal body weight, to keep plateau pressure < 30 cm H2O (4.0 kPa). MEASUREMENTS AND MAIN RESULTS: Mean tidal volumes during the first 5 days in traditional and small tidal volume patients were 10.2 and 7.3 mL/kg, respectively (p < .001), with mean plateau pressure = 30.6 and 24.9 cm H2O (3.3 kPa), respectively (p < .001). There were no significant differences in requirements for positive end-expiratory pressure or FIO2, fluid intakes/outputs, requirements for vasopressors, sedatives, or neuromuscular blocking agents, percentage of patients that achieved unassisted breathing, ventilator days, or mortality. CONCLUSIONS: The reduced tidal volume strategy used in this study was safe. Failure to observe beneficial effects of small tidal volume ventilation treatment in important clinical outcome variables may have occurred because a) the sample size was too small to discern small treatment effects; b) the differences in tidal volumes and plateau pressures were modest; or c) reduced tidal volume ventilation is not beneficial.