Effect of mechanical ventilation on cytokine response to intratracheal lipopolysaccharide

BACKGROUND: Mechanical ventilation may cause lung injury through the excitation of an inflammatory response and the release of mediators, such as cytokines. The authors tested the hypothesis that intratracheal lipopolysaccharide amplifies the cytokine response to mechanical ventilation. METHODS: Rat lungs were intratracheally instilled with lipopolysaccharide followed by ex vivo mechanical ventilation for 2 h with low tidal volume of 7 ml/kg with 3 cm H2O positive end-expiratory pressure (PEEP), high tidal volume of 40 ml/kg with zero PEEP, medium tidal volume of 15 ml/kg with 3 cm H2O PEEP, or medium tidal volume and zero PEEP. RESULTS: In the absence of lipopolysaccharide, lung lavage concentrations of tumor necrosis factor and interleukin 1 beta but not macrophage inflammatory protein 2 were significantly higher in lungs ventilated at high tidal volume/zero PEEP than at low tidal volume. There was a marked increase in lavage tumor necrosis factor and macrophage inflammatory protein 2 concentrations in lungs ventilated at low tidal volume after exposure to intratracheal lipopolysaccharide at doses of 100 ng/ml or greater. However, in lungs ventilated at high tidal volume, this response to lipopolysaccharide was markedly reduced. In addition, the number of alveolar macrophages recovered in the lavage was significantly lower in lungs ventilated at high tidal volume. CONCLUSION: Ventilation strategy can modify lung cytokine responses to lipopolysaccharide, likely through an effect on the alveolar macrophage population.     

Mechanical Ventilation with Lower Tidal Volumes and Positive End-expiratory Pressure Prevents Pulmonary Inflammation in Patients without Preexisting Lung Injury

Background: Mechanical ventilation with high tidal volumes aggravates lung injury in patients with acute lung injury or acute respiratory distress syndrome. The authors sought to determine the effects of short-term mechanical ventilation on local inflammatory responses in patients without preexisting lung injury.

Methods: Patients scheduled to undergo an elective surgical procedure (lasting >=5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h thereafter, bronchoalveolar lavage fluid and/or blood was investigated for polymorphonuclear cell influx, changes in levels of inflammatory markers, and nucleosomes.

Results: Mechanical ventilation with lower tidal volumes and PEEP (n = 21) attenuated the increase of pulmonary levels of interleukin (IL)-8, myeloperoxidase, and elastase as seen with higher tidal volumes and no PEEP (n = 19). Only for myeloperoxidase, a difference was found between the two ventilation strategies after 5 h of mechanical ventilation (P < 0.01). Levels of tumor necrosis factor [alpha], IL-1[alpha], IL-1[beta], IL-6, macrophage inflammatory protein 1[alpha], and macrophage inflammatory protein 1[beta] in the bronchoalveolar lavage fluid were not affected by mechanical ventilation. Plasma levels of IL-6 and IL-8 increased with mechanical ventilation, but there were no differences between the two ventilation groups.     

Mechanical ventilation affects lung function and cytokine production in an experimental model of endotoxemia

BACKGROUND: Mechanical ventilation using tidal volumes around 10 ml/kg and zero positive end-expiratory pressure is still commonly used in anesthesia. This strategy has been shown to aggravate lung injury and inflammation in preinjured lungs but not in healthy lungs. In this study, the authors investigated whether this strategy would result in lung injury during transient endotoxemia in the lungs of healthy animals. METHODS: Volume-controlled ventilation with a tidal volume of 10 ml/kg and zero positive end-expiratory pressure was applied in two groups of anesthetized-paralyzed rabbits receiving either intravenous injection of 5 mug/kg Escherichia coli lipopolysaccharide (n = 10) or saline (n = 10) 2 h after the start of mechanical ventilation. The third group consisted of 10 spontaneously breathing anesthetized animals receiving lipopolysaccharide. Anesthesia was then continued for 4 h in the three groups while the ventilatory modes were maintained unchanged. Lung injury was studied using blood gases, respiratory physiologic variables, analysis of the bronchoalveolar lavage cell counts, and cytokine concentrations and lung pathologic examination. RESULTS: Significant histologic lung alterations, hypoxemia, and altered lung mechanics were observed in rabbits treated with mechanical ventilation and intravenous lipopolysaccharide but not in the mechanically ventilated animals injected with saline or in spontaneously breathing animals treated with lipopolysaccharide. Endotoxemic ventilated animals also had significantly more lung inflammation as assessed by the alveolar concentration of neutrophils, and the concentrations of the chemokines interleukin 8 and growth-related oncogen alpha. CONCLUSIONS: These results showed that positive-pressure mechanical ventilation using a tidal volume of 10 ml/kg and zero positive end-expiratory pressure was harmful in the setting of endotoxemia, suggesting that the use of this ventilator strategy in the operating room may predispose to lung injury when endotoxemia occurs.     

Mechanical Ventilation Affects Lung Function and Cytokine Production in an Experimental Model of Endotoxemia

Background: Mechanical ventilation using tidal volumes around 10 ml/kg and zero positive end-expiratory pressure is still commonly used in anesthesia. This strategy has been shown to aggravate lung injury and inflammation in preinjured lungs but not in healthy lungs. In this study, the authors investigated whether this strategy would result in lung injury during transient endotoxemia in the lungs of healthy animals.

Methods: Volume-controlled ventilation with a tidal volume of 10 ml/kg and zero positive end-expiratory pressure was applied in two groups of anesthetized-paralyzed rabbits receiving either intravenous injection of 5 [mu]g/kg Escherichia coli lipopolysaccharide (n = 10) or saline (n = 10) 2 h after the start of mechanical ventilation. The third group consisted of 10 spontaneously breathing anesthetized animals receiving lipopolysaccharide. Anesthesia was then continued for 4 h in the three groups while the ventilatory modes were maintained unchanged. Lung injury was studied using blood gases, respiratory physiologic variables, analysis of the bronchoalveolar lavage cell counts, and cytokine concentrations and lung pathologic examination.

Results: Significant histologic lung alterations, hypoxemia, and altered lung mechanics were observed in rabbits treated with mechanical ventilation and intravenous lipopolysaccharide but not in the mechanically ventilated animals injected with saline or in spontaneously breathing animals treated with lipopolysaccharide. Endotoxemic ventilated animals also had significantly more lung inflammation as assessed by the alveolar concentration of neutrophils, and the concentrations of the chemokines interleukin 8 and growth-related oncogen [alpha].     

Mechanical ventilation affects inflammatory mediators in patients undergoing cardiopulmonary bypass for cardiac surgery: a randomized clinical trial

OBJECTIVES: Respiratory support for patients recovering from cardiopulmonary bypass and cardiac surgery uses large tidal volumes and a minimal level of positive end-expiratory pressure. Recent data indicate that these ventilator settings might cause pulmonary and systemic inflammation in patients with acute lung injury. We examined the hypothesis that high tidal volumes and low levels of positive end-expiratory pressure might worsen the inflammatory response associated to cardiopulmonary bypass. METHODS: Forty patients undergoing elective coronary artery bypass were randomized to be ventilated after cardiopulmonary bypass disconnection with high tidal volume/low positive end-expiratory pressure (10-12 mL/kg and 2-3 cm H2O, respectively) or low tidal volume/high positive end-expiratory pressure (8 mL/kg and 10 cm H2O, respectively). Interleukin 6 and interleukin 8 levels were measured in the bronchoalveolar lavage fluid and plasma. Samples were taken before sternotomy (time 0), immediately after cardiopulmonary bypass separation (time 1), and after 6 hours of mechanical ventilation (time 2). RESULTS: Interleukin 6 and interleukin 8 levels in the bronchoalveolar lavage fluid and plasma significantly increased at time 1 in both groups but further increased at time 2 only in patients ventilated with high tidal volume/low positive end-expiratory pressure. Interleukin 6 and interleukin 8 levels in the bronchoalveolar lavage fluid and in the plasma at time 2 were higher with high tidal volume/low positive end-expiratory pressure than with low tidal volume/high positive end-expiratory pressure. CONCLUSION: Mechanical ventilation might be a cofactor able to influence the inflammatory response after cardiac surgery.     

Inhibition of Poly(Adenosine Diphosphate-Ribose) Polymerase Attenuates Ventilator-induced Lung Injury

Background: Mechanical ventilation can induce organ injury associated with overwhelming inflammatory responses. Excessive activation of poly(adenosine diphosphate-ribose) polymerase enzyme after massive DNA damage may aggravate inflammatory responses. Therefore, the authors hypothesized that the pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase by PJ-34 would attenuate ventilator-induced lung injury.

Methods: Anesthetized rats were subjected to intratracheal instillation of lipopolysaccharide at a dose of 6 mg/kg. The animals were then randomly assigned to receive mechanical ventilation at either low tidal volume (6 ml/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (15 ml/kg) with zero positive end-expiratory pressure, in the presence and absence of intravenous administration of PJ-34.

Results: The high-tidal-volume ventilation resulted in an increase in poly(adenosine diphosphate-ribose) polymerase activity in the lung. The treatment with PJ-34 maintained a greater oxygenation and a lower airway plateau pressure than the vehicle control group. This was associated with a decreased level of interleukin 6, active plasminogen activator inhibitor 1 in the lung, attenuated leukocyte lung transmigration, and reduced pulmonary edema and apoptosis. The administration of PJ-34 also decreased the systemic levels of tumor necrosis factor [alpha] and interleukin 6, and attenuated the degree of apoptosis in the kidney.     

不同机械通气模式对老年腹部手术患者细胞因子的影响

目的探讨不同机械通气模式对于老年腹部手术患者细胞因子的影响。方法 72例择期进行腹部手术全麻机械通气的老年患者(年龄65岁)分为6组,每组12例。A组:VCV(Vt 6 m L/kg)+PEEP 8 mm Hg+auto-flow模式;B组:VCV(Vt 6 m L/kg)+PEEP 8 mm Hg+const-flow模式;C组:VCV(Vt 6 m L/kg)+PEEP 12 mm Hg+auto-flow模式;D组:VCV(Vt 6 m L/kg)+PEEP 12mm Hg+const-flow模式;E组:VCV(Vt 10 m L/kg)+auto-flow模式;F组:VCV(Vt 10 m L/kg)+const-flow模式。6组患者全身麻醉气管插管后,均予以VCV(Vt 6 m L/kg)+const-flow模式通气60 min,再按分组的通气模式进行通气,总通气时间大于5 h。在通气1 h及5 h两个时间点,抽取静脉血和支气管肺泡灌洗液检测IL-8、IL-10、MMP-9、SP-A以及SF浓度。结果大潮气量组(E、F两组)较小潮气量四组(A、B、C、D四组)通气5 h后,血与BALF中测定的IL-8、MMP-9浓度以及血中测定的SP-A、SF浓度明显升高(P0.05),血与BALF中测定的IL-10浓度以及BALF中测定的SP-A浓度明显降低(P0.05)。通气5 h后F组较E组,血及BALF中IL-8以及MMP-9、血SF、血SP-A更高(P0.05),而BALF中SP-A则更低(P0.05)。结论 (1)大潮气量机械通气较小潮气量机械通气而言,更有利于促进IL-8、MMP-9、SF的分泌,抑制IL-10的释放,BALF中SP-A下降,血中SP-A升高,进一步加剧了VILI的程度。(2)就老年(年龄65岁)腹部手术患者而言,围手术期以VCV(Vt6 m L/kg)+PEEP 12 mm Hg+auto-flow模式机械通气较其他五种通气模式,更有利于减轻肺组织急性炎症反应及氧化应激反应的激活,减轻机械通气所致生物伤,从而减轻VILI的程度。     

Intraoperative changes in arterial oxygenation during volume-controlled mechanical ventilation in modestly obese patients undergoing laparotomies with general anesthesia

BACKGROUND: In obese patients, arterial oxygenation can be greatly impaired during general anesthesia. Both avoidance of denitrogenation and application of positive end-expiratory pressure (PEEP) during mechanical ventilation may be effective in preventing such impairment of arterial oxygenation. METHODS: We studied 28 obese/overweight and seven non-obese (BMI < 25 kg x m-2) patients who underwent laparotomies with general anesthesia (i.e. isoflurane with or without nitrous oxide). During anesthesia, their lungs were mechanically ventilated at a rate of 10 breaths x min-1 with a constant flow, inspiratory-to-expiratory ratio 1 : 2, and tidal volume approximately 10 ml x kg-1. The obese/overweight patients were allocated to four different groups in terms of denitrogenation and application of PEEP (7 cm H2O) during the ventilation (n = 7 each). In the non-obese patients, their denitrogenated lungs were ventilated without application of PEEP. Arterial gas analyses were performed before induction of anesthesia, and 30, 90, 150 and 210 min after tracheal intubation. The ratio of PaO2 to FiO2 was calculated as an index of arterial oxygenation. RESULTS: No significant changes in the PaO2/FiO2 ratio were observed throughout the study in the non-obese patients and in the obese/overweight patients whose non-denitrogenated lungs were ventilated with PEEP. In the obese/overweight patients whose lungs were ventilated after denitrogenation or without application of PEEP, significant decreases in the PaO2/FiO2 ratio were observed 30 and 90 min after tracheal intubation. CONCLUSIONS: In obese or overweight patients under general anesthesia, it may be advisable to avoid denitrogenation and apply PEEP during mechanical ventilation in order to minimize the impairment of arterial oxygenation.     

Pressure controlled-inverse ratio ventilation and pulmonary gas exchange during lower abdominal surgery

Although pressure controlled-inverse ratio ventilation (PC-IRV) has been used successfully in the treatment of respiratory failure, it has not been applied to the treatment of respiratory dysfunction during anaesthesia. With PC-IRV the inspiratory wave form is fundamentally altered so that inspiratory time is prolonged (inverse I:E), inspiratory flow rate is low, and the peak inspiratory pressure is limited. Positive end-expiratory pressure (PEEP) can be applied and the mean airway pressure is higher than with conventional ventilation. To assess the clinical efficacy of this new mode of ventilation we studied ten patients having lower abdominal gynaecologic surgery in the Trendelenburg position under general anaesthesia. Pulmonary O2 exchange was determined during four steady states: awake control (AC), after 30 and 60 min of PC-IRV during surgery, and at the end of surgery. Patients' lungs were ventilated with air/O2 by a Siemens 900C servo ventilator in the PC-IRV mode with an I:E ratio of 2:1 and 5 cm H2O of PEEP. The FIO2 was controlled at 0.5 and arterial blood gases were used to calculate the oxygen tension-based indices of gas exchange. There were significant increases of (A-a) DO2 at 30 and 60 min (41 and 43%). These changes were less than those reported in a previous study using conventional tidal volume ventilation (7.5 ml.kg-1) and were similar to those in patients whose lungs were ventilated with high tidal volumes (12.7 ml.kg-1). Thus, in this clinical model of compromised gas exchange, arterial oxygenation was better with PC-IRV than with conventional ventilation, but not better than with large tidal volume ventilation.     

Different Ventilation Strategies Affect Lung Function but Do Not Increase Tumor Necrosis Factor-α and Prostacyclin Production in Lavaged Rat Lungs In Vivo

Background: Using an in vivo animal model of surfactant deficiency, the authors compared the effect of different ventilation strategies on oxygenation and inflammatory mediator release from the lung parenchyma.

Methods: In adult rats that were mechanically ventilated with 100% oxygen, acute lung injury was induced by repeated lung lavage to obtain an arterial oxygen partial pressure < 85 mmHg (peak pressure/positive end-expiratory pressure [PEEP] = 26/6 cm H2O). Animals were then randomly assigned to receive either exogenous surfactant therapy, partial liquid ventilation, ventilation with high PEEP (16 cm H2O), ventilation with low PEEP (8 cm H2O), or ventilation with an increase in peak inspiratory pressure (to 32 cm H2O; PEEP = 6 cm H2O). Two groups of healthy nonlavaged rats were ventilated at a peak pressure/PEEP of 32/6 and 32/0 cm H2O, respectively. Blood gases were measured. Prostacyclin (PGI2) and tumor necrosis factor-[alpha] (TNF-[alpha]) concentrations in serum and bronchoalveolar lavage fluid (BALF) as well as protein concentration in BALF were determined after 90 and 240 min and compared with mechanically ventilated and spontaneously breathing controls.

Results: Surfactant, partial liquid ventilation, and high PEEP improved oxygenation and reduced BALF protein levels. Ventilation with high PEEP at high mean airway pressure levels increased BALF PGI2 levels, whereas there was no difference in BALF TNF-[alpha] levels between groups. Serum PGI2 and TNF-[alpha] levels did not increase as a result of mechanical ventilation when compared with those of spontaneously breathing controls.     

Immediate effects of positive end-expiratory pressure and low and high tidal volume ventilation upon gas exchange and compliance in patients with acute lung injury.

BACKGROUND: Protective ventilation, in general, includes low tidal volume ventilation and maintaining end-inspiratory plateau pressures less than 35 cmH2O. Recent clinical studies have determined that such an approach results in improved survival in patients with moderate to severe acute lung injury and acute respiratory distress syndrome. However, experimental evidence suggests that repeated end-expiratory collapse and reexpansion contributes to ventilator-induced lung injury. We sought to determine the immediate effects of specific tidal volume-PEEP combinations upon oxygenation and static compliance in patients with moderate to severe acute lung injury. METHODS: Fourteen patients were prospectively studied and were treated with each of 10 tidal volume-PEEP combinations, applied in random order. After 5 minutes at each tidal volume-PEEP combination, PaO2/FIO2 and static compliance were recorded. Comparisons were made between low and high tidal volume ventilation as well as across five PEEP levels. RESULTS: At both low (6 mL/kg) and high (10 mL/kg) tidal volume ventilation, PaO2/FIO2 increased with increasing PEEP, up to 20 cmH2O. Similar changes in static compliance were not evident. Static compliance was highest at PEEP of 10 and 15 cmH2O, regardless of tidal volume. With PEEP set at 5 cmH2O, static compliance was significantly lower with 6 mL/kg than with 10 mL/kg tidal volumes. Overall, static compliance was lowest for both tidal volume conditions with PEEP set at 25 cmH2O. CONCLUSION: Low tidal volume ventilation with PEEP set at 5 cmH2O results in poor oxygenation and compliance in patients with moderate to severe acute lung injury. Similarly, PEEP set at 25 cmH2O did not improve oxygenation or compliance.     

全麻中低潮气量机械通气对病人肺泡不张发生的影响

目的 探讨全麻中低潮气量（VT）机械通气对病人肺泡不张发生的影响。方法 择期全麻下行开颅手术病人16例。ASAⅠ级或Ⅱ级，心功能Ⅰ级或Ⅱ级，年龄20-50岁，随机分为2组，每组8例，常规VT（10 ml／kg）组（TV组）和低VT（6 ml／kg）组（LV组）。分别于气管插管后10 min和手术结束后10min采用移动CT行全肺扫描，计算膈上1 cm层面肺不张面积和百分比，同时行动脉血气分析，记录动脉血二氧化碳分压（PaCO2），并计算肺泡．动脉血氧分压差[P（A-a），O2]、氧合指数（PaO2／FiO2）及呼吸指数（RI）。结果 气管插管后10 min和手术结束后10 min时2组病人肺泡不张的发生率、面积、百分比、P（A-a）O2、PaCO2、PaO2／FiO2及RI组内、组间差异均无统计学意义（P〉0．05）。结论 低VT （6 ml／kg）机械通气不增加全麻下开颅手术病人肺泡不张的发生。     

Different ventilation strategies affect lung function but do not increase tumor necrosis factor-alpha and prostacyclin production in lavaged rat lungs in vivo

BACKGROUND: Using an in vivo animal model of surfactant deficiency, the authors compared the effect of different ventilation strategies on oxygenation and inflammatory mediator release from the lung parenchyma. METHODS: In adult rats that were mechanically ventilated with 100% oxygen, acute lung injury was induced by repeated lung lavage to obtain an arterial oxygen partial pressure < 85 mmHg (peak pressure/positive end-expiratory pressure [PEEP] = 26/6 cm H2O). Animals were then randomly assigned to receive either exogenous surfactant therapy, partial liquid ventilation, ventilation with high PEEP (16 cm H2O), ventilation with low PEEP (8 cm H2O), or ventilation with an increase in peak inspiratory pressure (to 32 cm H2O; PEEP = 6 cm H2O). Two groups of healthy nonlavaged rats were ventilated at a peak pressure/PEEP of 32/6 and 32/0 cm H2O, respectively. Blood gases were measured. Prostacyclin (PGI2) and tumor necrosis factor-alpha (TNF-alpha) concentrations in serum and bronchoalveolar lavage fluid (BALF) as well as protein concentration in BALF were determined after 90 and 240 min and compared with mechanically ventilated and spontaneously breathing controls. RESULTS: Surfactant, partial liquid ventilation, and high PEEP improved oxygenation and reduced BALF protein levels. Ventilation with high PEEP at high mean airway pressure levels increased BALF PGI2 levels, whereas there was no difference in BALF TNF-alpha levels between groups. Serum PGI2 and TNF-alpha levels did not increase as a result of mechanical ventilation when compared with those of spontaneously breathing controls. CONCLUSIONS: Although alveolar protein concentration and oxygenation markedly differed with different ventilation strategies in this model of acute lung injury, there were no indications of ventilation-induced systemic PGI2 and TNF-alpha release, nor of pulmonary TNF-alpha release. Mechanical ventilation at high mean airway pressure levels increased PGI2 levels in the bronchoalveolar lavage-accessible space.     

Ventilation with negative airway pressure induces a cytokine response in isolated mouse lung

We tested the hypothesis that, under relatively low tidal volume (VT) mechanical ventilation, continuing lung decruitment induced by negative end-expiratory pressure (NEEP) would increase the lung cytokine response, potentially contributing to lung injury. Mouse lungs were excised and randomly assigned to one of 3 different ventilatory strategies: 1) the zero end-expiratory pressure group served as a control, 2) the NEEP7 group received a NEEP of -7.5 cm H(2)O, and 3) the NEEP15 group received a NEEP of -15 cm H(2)O. In all 3 groups, a VT of 7 mL/kg was used. After 2 h of ventilation, lung lavage fluid was collected for measurements of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and lactate dehydrogenase. Increases in plateau pressure before and after mechanical ventilation were significantly greater in the NEEP15 group compared with the zero end-expiratory pressure group or NEEP7 group. Lung compliance was decreased in the NEEP15 compared with the other two groups. Concentrations of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and lactate dehydrogenase in lung lavage were larger in the NEEP15 group than in the other groups. Atelectatic lung during repeated collapse and reopening of lung units accentuates the lung cytokine response that may contribute to lung injury even during relatively low VT mechanical ventilation. IMPLICATIONS: Repeated closing and reopening of lung units induced by negative end-expiratory pressure resulted in lung inflammation and cell injury even under mechanical ventilation using a normal tidal volume. This finding may have clinical relevance in certain patients who are prone to atelectasis during mechanical ventilation.     

不同机械通气方式对冠状动脉旁路移植术后机体炎症介质浓度的影响

目的 观察大潮气量低呼吸终末压力(H.Vt/L-PEEP)和低潮气量高呼吸终末压力(LwH_PEEP)两种不同机械通气方式对冠状动脉旁路移植术后机体炎症介质IL--6和IL-8浓度的影响,寻找冠状动脉旁路移植术后更为合理的机械通气方式.方法 40例择期行冠状动脉旁路移植术者在相同的麻醉和体外循环条件下,按大潮气量低呼吸终末压力和低潮气量高呼吸终末压力机械通气方式随机分为两组,分别于开胸前(TO)、体外循环结束(T1)、体外循环停止机械通气6 h(r12)采集支气管灌洗液和中心静脉血样本,观察3个时点两组Ⅱ,6及IL-8在支气管灌洗液和血浆中的浓度变化.结果 两组支气管灌洗液及血浆炎症介质IL-6、IL-8浓度在Tl时显著增高.机械通气6 h后(12)L-VdH.PEEP组支气管灌洗液及血浆Ⅱ,6、IL-8浓度无明显改变,而H-VdL-PEEP组则显著升高(P相似文献   

Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents alveolar coagulation in patients without lung injury

BACKGROUND: Alveolar fibrin deposition is a hallmark of acute lung injury, resulting from activation of coagulation and inhibition of fibrinolysis. Previous studies have shown that mechanical ventilation with high tidal volumes may aggravate lung injury in patients with sepsis and acute lung injury. The authors sought to determine the effects of mechanical ventilation on the alveolar hemostatic balance in patients without preexistent lung injury. METHODS: Patients scheduled for an elective surgical procedure (lasting > or = 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h later bronchoalveolar lavage fluid and blood samples were obtained, and markers of coagulation and fibrinolysis were measured. RESULTS: In contrast to mechanical ventilation with lower tidal volumes and PEEP (n = 21), the use of higher tidal volumes without PEEP (n = 19) caused activation of bronchoalveolar coagulation, as reflected by a marked increase in thrombin-antithrombin complexes, soluble tissue factor, and factor VIIa after 5 h of mechanical ventilation. Mechanical ventilation with higher tidal volumes without PEEP caused an increase in soluble thrombomodulin in lavage fluids and lower levels of bronchoalveolar activated protein C in comparison with lower tidal volumes and PEEP. Bronchoalveolar fibrinolytic activity did not change by either ventilation strategy. CONCLUSIONS: Mechanical ventilation with higher tidal volumes and no PEEP promotes procoagulant changes, which are largely prevented by the use of lower tidal volumes and PEEP.     

Effects of end-inspiratory and end-expiratory pressures on alveolar recruitment and derecruitment in saline-washout-induced lung injury -- a computed tomography study

BACKGROUND: Lung protective ventilation using low end-inspiratory pressures and tidal volumes (VT) has been shown to impair alveolar recruitment and to promote derecruitment in acute lung injury. The aim of the present study was to compare the effects of two different end-inspiratory pressure levels on alveolar recruitment, alveolar derecruitment and potential overdistention at incremental levels of positive end-expiratory pressure. METHODS: Sixteen adult sheep were randomized to be ventilated with a peak inspiratory pressure of either 35 cm H2O (P35, low VT) or 45 cm H2O (P45, high VT) after saline washout-induced lung injury. Positive end-expiratory pressure (PEEP) was increased in a stepwise manner from zero (ZEEP) to 7, 14 and 21 cm of H2O in hourly intervals. Tidal volume, initially set to 12 ml kg(-1), was reduced according to the pressure limits. Computed tomographic scans during end-expiratory and end-inspiratory hold were performed along with hemodynamic and respiratory measurements at each level of PEEP. RESULTS: Tidal volumes for the two groups (P35/P45) were: 7.7 +/- 0.9/11.2 +/- 1.3 ml kg(-1) (ZEEP), 7.9 +/- 2.1/11.3 +/- 1.3 ml kg(-1) (PEEP 7 cm H2O), 8.3 +/- 2.5/11.6 +/- 1.4 ml kg(-1) (PEEP 14 cm H2O) and 6.5 +/- 1.7/11.0 +/- 1.6 ml kg(-1) (PEEP 21 cm H2O); P < 0.001 for differences between the two groups. Absolute nonaerated lung volumes during end-expiration and end-inspiration showed no difference between the two groups for given levels of PEEP, while tidal-induced changes in nonaerated lung volume (termed cyclic alveolar instability, CAI) were larger in the P45 group at low levels of PEEP. The decrease in nonaerated lung volume was significant for PEEP 14 and 21 cm H2O in both groups compared with ZEEP (P < 0.005). Over-inflated lung volumes, although small, were significantly higher in the P45 group. Significant respiratory acidosis was noted in the P35 group despite increases in the respiratory rate. CONCLUSION: Limiting peak inspiratory pressure and VT does not impair alveolar recruitment or promote derecruitment when using sufficient levels of PEEP.     

The pulmonary immune effects of mechanical ventilation in patients undergoing thoracic surgery

Mechanical ventilation (MV) may induce an inflammatory alveolar response. One-lung ventilation (OLV) with tidal volumes (Vt) as used during two-lung ventilation is a suggested algorithm but may impose mechanical stress of the dependent lung and potentially aggravate alveolar mediator release. We studied whether ventilation with different Vt modifies pulmonary immune function, hemodynamics, and gas exchange. Thirty-two patients undergoing open thoracic surgery were randomized to receive either MV with Vt = 10 mL/kg (n = 16) or Vt = 5 mL/kg (n = 16) adjusted to normal Pa(CO2) during and after OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed, and cells, protein, tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, soluble intercellular adhesion molecule (sICAM)-1, IL-10, and elastase were determined in the bronchoalveolar lavage. Data were analyzed by parametric or nonparametric tests, as indicated. In all patients, an increase of proinflammatory variables was found. The time courses of intra-alveolar cells, protein, albumin, IL-8, elastase, and IL-10 did not differ between the groups after OLV and postoperatively. TNF-alpha (8.4 versus 5.0 microg/mL) and sICAM-1 (52.7 versus 27.5 microg/mL) concentrations were significantly smaller after OLV with Vt = 5 mL/kg. These results indicate that MV may induce epithelial damage and a proinflammatory response in the ventilated lung. Reduction of tidal volume during OLV may reduce alveolar concentrations of TNF-alpha and of sICAM-1. IMPLICATIONS: Reductions of tidal volume, with subsequently decreased peak airway pressures, may reduce some alveolar inflammatory responses seen with mechanical ventilation.     

Mechanical Ventilation with Lower Tidal Volumes and Positive End-expiratory Pressure Prevents Alveolar Coagulation in Patients without Lung Injury

Background: Alveolar fibrin deposition is a hallmark of acute lung injury, resulting from activation of coagulation and inhibition of fibrinolysis. Previous studies have shown that mechanical ventilation with high tidal volumes may aggravate lung injury in patients with sepsis and acute lung injury. The authors sought to determine the effects of mechanical ventilation on the alveolar hemostatic balance in patients without preexistent lung injury.

Methods: Patients scheduled for an elective surgical procedure (lasting >= 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h later bronchoalveolar lavage fluid and blood samples were obtained, and markers of coagulation and fibrinolysis were measured.

Results: In contrast to mechanical ventilation with lower tidal volumes and PEEP (n = 21), the use of higher tidal volumes without PEEP (n = 19) caused activation of bronchoalveolar coagulation, as reflected by a marked increase in thrombin-antithrombin complexes, soluble tissue factor, and factor VIIa after 5 h of mechanical ventilation. Mechanical ventilation with higher tidal volumes without PEEP caused an increase in soluble thrombomodulin in lavage fluids and lower levels of bronchoalveolar activated protein C in comparison with lower tidal volumes and PEEP. Bronchoalveolar fibrinolytic activity did not change by either ventilation strategy.     

Partial liquid ventilation with perfluorocarbons for treatment of ARDS in burns

Pulmonary failure remains the major determinant of mortality and morbidity following burn injury. We hypothesized that intratracheal instillation of perfluorocarbon liquids could be a therapeutic measure in combination with conventional mechanical ventilation to improve pulmonary gas exchange in acute respiratory distress syndrome with thermal injury. Forty-five New Zealand rabbits were used for this prospective and randomized experimental study. The animals were burned by scald to reach full-thickness 40% burn surface area. After inducing respiratory distress by repeated lung lavage with saline, animals were divided randomly into three groups of 15 rabbits each. First group (control group) received conventional treatment (continuous positive-pressure ventilation) using a FiO(2) of 1.0, tidal volume of 12 ml/kg, respiratory frequency of 30 cycles/min and PEEP of 6 cm H(2)O. Second group was treated with 9 ml/kg of intratracheal perfluorocarbon. Third group was treated with 15 ml/kg of intratracheal perfluorocarbon. All groups were ventilated for 6 h. In the perfluorocarbon groups, PaO(2) increased significantly (P<0.05) from 46+/-4 to 439+/-10 mmHg compared to the control group in a dose-related manner. In pulmonary parameters we observed significant (P<0.05) decrease in mean airway pressures from the pre-treatment value of 11.44+/-0.15 cm H(2)O to the post treatment 10.22+/-0.12 cm H(2)O and increase (P<0.05) in respiratory system compliance from 1.8+/-0.02 to 2.46+/-0.07 ml/cm H(2)O with the perfluorocarbon. Perfluorocarbon instillation did not result in statistically significant changes in arterial pressure, heart rate and central venous pressure. In conclusion, partial liquid ventilation with perfluorocarbon is a new technique leading to a marked and sustained improvement in oxygenation and pulmonary function in an experimental model of ARDS in burns.