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.     

Warning! Suctioning. A lung model evaluation of closed suctioning systems

BACKGROUND: Closed system suctioning, CSS, has been advocated to avoid alveolar collapse. However, ventilator manufacturers indicate that extreme negative pressure levels can be obtained during closed system suctioning, impeding the performance of the ventilator. METHODS: Suctioning with a 12 or 14 Fr catheter with a vacuum level of -50 kPa was either performed with an open technology or a CSS, where the catheter is introduced through a tight-fitting connection through the endotracheal tube, EYT. The lung model was ventilated with a Servo 900C or 300 ventilator with an I:E ratio of 1:2, 1:1 and 2:1 and extrinsic positive end-expiratory pressure (PEEP) at 0 or 10 cm H20. Respiratory volumes and alveolar pressure were measured at the lung model alveolus. RESULTS: The initial suctioning flow was >40 l/min with a 14 Fr catheter. When inserting the catheter through a no. 7 ETT, PEEP rose from 11 to 23 cm H2O during volume control ventilation with an I:E ratio 1:1. During suctioning the alveolar pressure fell to 10 cm H2O below the set PEEP level. CSS during pressure control ventilation had fewer effects. Low tidal volumes, inverse I:E ratio and secretions in the tube resulted in pressures down to -92 cm H2O. CONCLUSION: CSS should not be used in volume control ventilation due to risk of high intrinsic PEEP levels at insertion of the catheter and extreme negative pressures during suctioning. Pressure control ventilation produces less intrinsic PEEP effect. The continuous positive airway pressure (CPAP) mode offers the least intrinsic PEEP during insertion of the catheter and least sub-atmospheric pressure during suctioning.     

Visual validation of the mechanical stabilizing effects of positive end-expiratory pressure at the alveolar level

BACKGROUND: Positive end-expiratory pressure (PEEP) reduces ventilator-induced lung injury (VILI), presumably by mechanically stabilizing alveoli and decreasing intrapulmonary shear. Although there is indirect support for this concept in the literature, direct evidence is lacking. In a surfactant depletion model of acute lung injury we observed unstable alveolar mechanics referred to as repeated alveolar collapse and expansion (RACE) as measured by changes in alveolar area from inspiration to expiration (I - E(Delta)). We tested the hypothesis that over a range of tidal volumes PEEP would prevent RACE by mechanically stabilizing alveoli. MATERIALS AND METHODS: Yorkshire pigs were randomized to three groups: control (n = 4), Tween (surfactant-deactivating detergent) (n = 4), and Tween + PEEP (7 cm H(2)O) (n = 4). Using in vivo video microscopy individual alveolar areas were measured with computer image analysis at end inspiration and expiration over consecutive increases in tidal volume (7, 10, 15, 20, and 30 cc/kg.) I - E(Delta) was calculated for each alveolus. RESULTS: Surfactant deactivation significantly increased I - E(Delta) at every tidal volume compared to controls (P < 0.05). PEEP prevented this change, returning I - E(Delta) to control levels over a spectrum of tidal volumes. CONCLUSIONS: RACE occurs in our surfactant deactivation model of acute lung injury. PEEP mechanically stabilizes alveoli and prevents RACE over a range of tidal volumes. This is the first study to visually document the existence of RACE and the mechanical stabilizing effects of PEEP at the alveolar level. The ability of PEEP to stabilize alveoli and reduce shear during mechanical ventilation has important implications for therapeutic strategies directed at VILI and acute respiratory distress syndrome.     

Experimental studies on lung mechanics, gas exchange and oxygen delivery under open lung conditions Mechanical ventilation with decelerating versus constant inspiratory flow

The treatment of patients with acute respiratory failure poses an ever-present clinical challenge since conventional ventilation sometimes causes further impairment of lung function. Thus, it is important to identify characteristics of different ventilatory patterns and ventilatory strategies that affect airway pressures, lung volumes, pulmonary gas exchange and hemodynamics. In order to mimic acute respiratory failure in the patient, we have used an experimental animal injury model, characterized by highly unstable alveoli. The basic prerequisite for this thesis was a positive end-expiratory pressure (PEEP) sufficient to keep the lung open throughout the whole ventilatory cycle. Different inspiratory flow patterns were studied by using a successful recruitment procedure together with ventilation performed using PEEP levels below, at, and above the inflection-point pressure. To elucidate the effect of prolonged inspiration time, sufficient PEEP was supplied to prevent end-expiratory collapse already during the reference mode with an inspiration/expiration ratio (I:E ratio) of 1:1. When an I:E ratio of 2:1 or above was used, both studies (one with mean airway pressure constant and the other with total PEEP constant) showed impaired hemodynamics, but displayed unaffected arterial oxygen tension. Decelerating inspiratory flow delivers the major part of the tidal volume during early inspiration under sustained constant inspiratory pressure. This reduces serial dead space and improves alveolar ventilation. In all studies, decelerating inspiratory flow showed increased carbon dioxide elimination, i.e. improved alveolar ventilation, but decelerating inspiratory flow was found to be no better for alveolar recruitment or in oxygenation. In an attempt to explain radiological observations when studying the relationship of pulmonary radiological appearance to end-expiratory pressure, Staubs' concept of quantal alveolar behavior was used. This states that the individual alveolus fills essentially independently of its neighbors and has a propensity to be either air-filled and expanded, or completely fluid-filled and collapsed. Stepwise sequential deflation of the lung from full expansion, followed by stepwise inflation of the lung, produced a pressure/attenuation loop. This hysteresis phenomenon implies that the attenuation of the lung relates to the set PEEP, but also to the immediately preceding structural status. For identical end-expiratory pressures the attenuation on the hysteresis down-slope invariably had a higher value than that of the up-slope. Thus, the pressure at which alveolar collapse takes place differs from that of expansion. In conclusion, ventilation with decelerating inspiratory flow revealed lower peak inspiratory and higher mean airway pressure than did constant inspiratory flow. No differences in end-inspiratory pressure were seen. Decelerating inspiratory flow delivers the major part of the tidal volume during early inspiration, which reduces serial dead space and improves alveolar ventilation. The decelerating inspiratory flow was found to be no better than constant inspiratory flow for alveolar recruitment or oxygenation. When the lung was ventilated with PEEP sufficient to prevent end-expiratory collapse, an inspiration-to-expiration ratio at and above 2:1 impaired hemodynamics. Our results suggest that, in order to obtain and maintain open lung conditions, the lung must be recruited and PEEP reduced to the level just above the alveolar collapse pressure.     

利用动态肺顺应性设定呼气末正压在胸腔镜肺叶切除术中的运用

目的 探讨单肺通气利用动态肺顺应性设定呼气末正压通气(positive end-expiratory pressure,PEEP)的优势及可行性. 方法 选择预行右侧肺叶切除患者80例,完全随机分为A组和B组,每组40例:A组,单肺通气实施肺膨胀(sustained inflation,SI)复张后加用20 cmH2O(1 cmH2O=0.098 kPa)的PEEP并递减滴定,随后以得到最大肺顺应性的PEEP值通气,直到恢复双肺通气;B组,通气PEEP值固定为5 cmH2O,其他通气方法同A组.记录患者血气、呼吸等参数. 结果 两组设定的PEEP值[A组(9.2±1.2) cmH2O,B组5 cmH2O]差异有统计学意义(P＜0.05);在单肺通气1 h(T3)、手术结束(T4)时,两组动脉血氧分压(partial pressure of oxygen,PaO2)比较,差异有统计学意义(P＜0.05);B组的PaO2在T3～T4逐步降低,差异有统计学意义(P＜0.05),而A组则维持较好(P＞0.05);T3、T4时刻A组的动态肺顺应性[(30.8±5.9)、(30.7±6.4) ml/cmH2O]与B组[(26.6±5.5)、(26.4±5.2) ml/cmH2O]比较,差异有统计学意义(P＜0.05). 结论 胸腔镜肺叶切除术中的单肺通气,利用动态肺顺应性设定的PEEP值通气能够得到更好的氧合及呼吸参数,并且维持较好.     

Differential Lung Ventilation with Unilateral PEEP Following Unilateral Hydrochloric Acid Aspiration in the Dog

Differential lung ventilation with positive end expiratory pressure (PEEP) improves pulmonary gas exchange when used in the supportive care of patients with severe unilateral or asymmetrical lung disease. Once the provision of selective PEEP to the two lungs is accomplished, the best method of partitioning the tidal volume between the two lungs is unknown. Twelve mongrel dogs were given a unilateral hydrochloric acid (HCl) aspiration injury. A computer controlled differential lung ventilation system was used to ventilate four dogs with equal volumes to each lung, four dogs with equal driving pressure (end inspiratory pressure-PEEP) to each lung, and four dogs with equal end-tidal CO₂ fraction from each lung. The respiratory rate was feedback controlled to maintain Paco₂ at 4.67 kPa. The dogs were kept supine and ventilated with 30% O₂. Following injury, the PEEP was set at 0 kPa for 1 h. The dogs were then given 1.36 kPa and 2.72 kPa PEEP to the injured lung for 2 h in a cross-over fashion. The assignment of the tidal volume controller, the side of injury, and the PEEP sequence was random. Oxygen tension fell and pulmonary venous admixture increased after giving the HCl injury. In all three groups considered simultaneously, unilateral PEEP improved Pao₂ and venous admixture. The equal tidal volume distribution was the only group to show a significant improvement in Pao₂ at both PEEP increments (0 to 1.36 kPa and 2.72 kPa). There was a significant difference in tidal volume allocation between the three groups with the equal end-tidal and equal pause pressure groups only minimally ventilating the injured lung. With differential lung ventilation and unilateral PEEP, equal partitioning of tidal volume provides the highest Pao₂, compared to the other two methods of partitioning tidal volume.     

Respiratory and haemodynamic effects of conventional volume controlled PEEP ventilation, pressure regulated volume controlled ventilation and low frequency positive pressure ventilation with extracorporeal carbon dioxide removal in pigs with acute ARDS

The purpose of this study was to evaluate whether any benefit of low frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV–ECCO₂R) existed over either volume controlled ventilation (VCV) with measured best–PEEP or pressure regulated volume controlled ventilation (PRVCV) with an inspiration/expiration (I/E) ratio of 4:1, with respect to arterial oxygenation, lung mechanics and haemodynamics, in acute respiratory failure.
Fifteen adult pigs were used for the study. Respiratory failure was induced by surfactant depletion by repeated lung lavage. The different therapeutic approaches were applied randomly to each pig for 1 h. Measurements of gas exchange, airway pressures and haemodynamics were performed during ventilatory and haemodynamic steady state. Paco₂ was kept constant in all modes.
At almost similar total–PEEP, Pao₂ values were significantly higher with LFPPV–ECCO₂R comared to VCV with best–PEEP. Peak inspiratory pressure (PIP) and intrapulmonary pressure amplitude defined as the difference between PIP and total–PEEP were significantly lower with PRVCV and LFPPV–ECCO₂R compared to VCV with best–PEEP. There was no significant difference between the modes concerning cardiocircu–latory parameters.
PRVCV with I/E ratio of 4:1 and LFPPV–ECCO₂R proved to be better modes to achieve better gas exchange and lower PIP at lower intrapulmonary pressure amplitudes. It is concluded that PRVCV is an adequate form of treatment under these experimental conditions imitating acute respiratory failure, without necessitating other invasive measures.     

Capnography reflects ventilation/perfusion distribution in a model of acute lung injury

Background: Changes in the shape of the capnogram may reflect changes in lung physiology. We studied the effect of different ventilation/perfusion ratios (V/Q) induced by positive end‐expiratory pressures (PEEP) and lung recruitment on phase III slope (S_III) of volumetric capnograms. Methods: Seven lung‐lavaged pigs received volume control ventilation at tidal volumes of 6 ml/kg. After a lung recruitment maneuver, open‐lung PEEP (OL‐PEEP) was defined at 2 cmH₂O above the PEEP at the onset of lung collapse as identified by the maximum respiratory compliance during a decremental PEEP trial. Thereafter, six distinct PEEP levels either at OL‐PEEP, 4 cmH₂O above or below this level were applied in a random order, either with or without a prior lung recruitment maneuver. Ventilation–perfusion distribution (using multiple inert gas elimination technique), hemodynamics, blood gases and volumetric capnography data were recorded at the end of each condition (minute 40). Results: S _III showed the lowest value whenever lung recruitment and OL‐PEEP were jointly applied and was associated with the lowest dispersion of ventilation and perfusion (Disp_R?E), the lowest ratio of alveolar dead space to alveolar tidal volume (VD_alv/VT_alv) and the lowest difference between arterial and end‐tidal pCO₂ (Pa?ETCO₂). Spearman's rank correlations between S_III and Disp_R?E showed a ρ=0.85 with 95% CI for ρ (Fisher's Z‐transformation) of 0.74–0.91, P<0.0001. Conclusion: In this experimental model of lung injury, changes in the phase III slope of the capnograms were directly correlated with the degree of ventilation/perfusion dispersion.     

One-lung ventilation with high tidal volumes and zero positive end-expiratory pressure is injurious in the isolated rabbit lung model

We tested the hypothesis that one-lung ventilation (OLV) with high tidal volumes (VT) and zero positive end-expiratory pressure (PEEP) may lead to ventilator-induced lung injury. In an isolated, perfused rabbit lung model, VT and PEEP were set to avoid lung collapse and overdistension in both lungs, resulting in a straight pressure-time (P-vs-t) curve during constant flow. Animals were randomized to (a) nonprotective OLV (left lung) (n = 6), with VT values as high as before randomization and zero PEEP; (b) protective OLV (left lung) (n = 6), with 50% reduction of VT and maintenance of PEEP as before randomization; and (c) control group (n = 6), with ventilation of two lungs as before randomization. The nonprotective OLV was associated with significantly smaller degrees of collapse and overdistension in the ventilated lung (P < 0.001). Peak inspiratory pressure values were higher in the nonprotective OLV group (P < 0.001) and increased progressively throughout the observation period (P < 0.01). The mean pulmonary artery pressure and lung weight gain values, as well as the concentration of thromboxane B(2), were comparatively higher in the nonprotective OLV group (P < 0.05). A ventilatory strategy with VT values as high as those used in the clinical setting and zero PEEP leads to ventilator-induced lung injury in this model of OLV, but this can be minimized with VT and PEEP values set to avoid lung overdistension and collapse. IMPLICATIONS: One-lung ventilation with high tidal volumes and zero positive end-expiratory pressure (PEEP) is injurious in the isolated rabbit lung model. A ventilatory strategy with tidal volumes and PEEP set to avoid lung overdistension and collapse minimizes lung injury during one-lung ventilation in this model.     

不同通气方式对小儿心内直视手术期间Crs改变的初步观察

目的 小儿心内直视手术麻醉期间应用ＰＥＥＰ和转流期间肺泡低压,寻找此类手术麻醉中改善肺表面活性物质（ＰＳ）生成和呼吸系统总顺应性（Ｃｒｓ）的途径。方法 ４０例左向右分流型先心病患儿随机分为４组,Ｉ组为ＩＰＰＶ通气组,ＩＩ组ＰＥＥＰ应用组,Ⅲ组为ＩＰＰＶ通气且转流期间肺泡低压组,ＩＶ组为ＰＥＥＰ及转流期间肺泡低压组,测定各组各时点的Ｃｒｓ及ＰＳ生化指标,结果 Ｉ组手术结束时Ｃｒｓ,饱和磷／总磷及饱和     

Oleic acid lung injury: a morphometric analysis using computed tomography

BACKGROUND: The oleic acid-induced lung injury (OAI) model is considered to represent the early phase of acute respiratory distress syndrome (ARDS). Its inherent properties are important for the design and the interpretation of interventional studies. The aim of this study was to describe the evolution of morphometric lung changes during OAI using computed tomography (CT) analysis. Furthermore, the effect of a temporary change in positive end-expiratory pressure (PEEP) was evaluated. METHODS: Fifteen anaesthetized pigs were ventilated in volume-controlled mode with a baseline PEEP of 5 cm H(2)O. Helical CT scans were taken at baseline and 1 h after oleic acid injection. The PEEP was then either increased to 10 cm H(2)O (n = 5), decreased to 0 cm H(2)O (n = 5) or kept constant (n = 5) for 30 min. For the next 30 min, the baseline PEEP level was applied in all animals before the final CT scans 2 h after the induction of OAI. Dimensional and volumetric changes were determined from radiographical attenuation values. RESULTS: There was a major decrease in gas volume and an increase in tissue volume within the first hour. A net increase in total lung volume, with a larger transverse area but no displacement of the diaphragm, was manifest after 2 h. A minor increase in volume of non-aerated lung, located to the caudal region, was observed during the second hour. The tidal volume was redistributed to the middle and apical regions. The temporary change in PEEP did not influence the morphological progress of OAI. CONCLUSION: Decreased gas volume and increased tissue volume are the dominating morphometric characteristics of oleic acid lung injury, occurring mainly within the first hour. With these changes manifest, the course of injury is not affected by a limited period of moderately changed PEEP during the second hour. The net increase of total lung volume suggests a predominance of oedema formation over airway and alveolar collapse.     

Pulmonary effects of body position, PEEP, and surfactant depletion in dogs

The influence of position (sphinx, lateral, supine), surfactant depletion, and different positive end-expiratory pressure (PEEP) on functional residual capacity (FRC), series dead space (VdS) and compliance of the respiratory system (Crs) were evaluated in five dogs. Ventilation homogeneity as measured by an index (multiple breath alveolar mixing efficiency), oxygenation, and cardiovascular hemodynamics were additionally examined. The dogs were anesthetized with halothane, paralyzed, and mechanically ventilated. FRC and VdS were found to be notably large in dogs, 45 +/- 8 ml/kg and 6 +/- 1 ml/kg, respectively. FRC and ventilation homogeneity were improved in the sphinx position (prone position with upright head). Surfactant depletion by lung lavage with 37 degrees C saline caused an immediate and stable decrease in FRC, Crs, and oxygenation (P less than 0.05, respectively) for about 5 h without marked effects on the circulatory system. FRC and VdS increased with increasing PEEP. At the highest PEEP, 10 cmH2O (1 kPa), Crs decreased (P less than 0.05) and ventilation became more uneven, indicating alveolar overdistension.     

Comparison of exogenous surfactant therapy, mechanical ventilation with high end-expiratory pressure and partial liquid ventilation in a model of acute lung injury

We have compared three treatment strategies, that aim to prevent repetitive alveolar collapse, for their effect on gas exchange, lung mechanics, lung injury, protein transfer into the alveoli and surfactant system, in a model of acute lung injury. In adult rats, the lungs were ventilated mechanically with 100% oxygen and a PEEP of 6 cm H2O, and acute lung injury was induced by repeated lung lavage to obtain a PaO2 value < 13 kPa. Animals were then allocated randomly (n = 12 in each group) to receive exogenous surfactant therapy, ventilation with high PEEP (18 cm H2O), partial liquid ventilation or ventilation with low PEEP (8 cm H2O) (ventilated controls). Blood-gas values were measured hourly. At the end of the 4-h study, in six animals per group, pressure-volume curves were constructed and bronchoalveolar lavage (BAL) was performed, whereas in the remaining animals lung injury was assessed. In the ventilated control group, arterial oxygenation did not improve and protein concentration of BAL and conversion of active to non-active surfactant components increased significantly. In the three treatment groups, PaO2 increased rapidly to > 50 kPa and remained stable over the next 4 h. The protein concentration of BAL fluid increased significantly only in the partial liquid ventilation group. Conversion of active to non-active surfactant components increased significantly in the partial liquid ventilation group and in the group ventilated with high PEEP. In the surfactant group and partial liquid ventilation groups, less lung injury was found compared with the ventilated control group and the group ventilated with high PEEP. We conclude that although all three strategies improved PaO2 to > 50 kPa, the impact on protein transfer into the alveoli, surfactant system and lung injury differed markedly.      

Maximal hysteresis: a new method to set positive end‐expiratory pressure in acute lung injury?

Background: No methods are superior when setting positive end-expiratory pressure (PEEP) in acute lung injury (ALI). In ALI, the vertical distance (hysteresis) between the inspiratory and expiratory limbs of a static pressure–volume (PV) loop mainly indicates lung recruitment. We hypothesized that PEEP set at the pressure where hysteresis is 90% of its maximum (90%MH) would give similar oxygenation, but less cardiovascular depression than PEEP set at the pressure at lower inflection point (LIP) on the inspiratory limb or at the point of maximal curvature (PMC) on the expiratory limb in ALI.
Methods: In 12 mechanically ventilated pigs, ALI was induced in a randomized fashion by lung lavage, lung lavage plus injurious ventilation, or by oleic acid. From a static PV loop obtained by an interrupted low-flow method, the pressures at LIP [25 (25, 25) cmH₂O, mean and 25, 75 percentiles], at PMC [24 (20, 24) cmH₂O], and at 90% MH [19 (18, 19) cmH₂O] were determined and used for the PEEP-settings. We measured lung inflation (by computed tomography), end-expiratory lung volume (EELV), airway pressures, compliance of the respiratory system (Crs), blood gases, cardiac output and arterial blood pressure.
Results: There were no differences between the PEEP settings in EELV or oxygenation, but the 90%MH setting gave lower end-inspiratory pause pressure ( P <0.025), higher Crs ( P <0.025), less hyper-aeration ( P <0.025) and better maintained hemodynamics.
Conclusion: In this porcine lung injury model, PEEP set at 90% MH gave better lung mechanics and hemodynamics, than PEEP set at PMC or LIP.     

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.     

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.     

Delayed derecruitment after removal of PEEP in patients with acute lung injury

Background: A step decrease in positive end-expiratory airway pressure (PEEP) is not followed by an instantaneous loss of the PEEP-induced increase in end-expiratory lung volume (EELV). Rather, the reduction of EELV is delayed, while adverse PEEP effects on hemodynamics are immediately attenuated upon the drop in airway pressure. Step PEEP increments were applied to the lungs of patients with acute lung injury. It was investigated retrospectively whether enlargement of end-expiratory lung volume and changes in lung mechanics persist 45 min after removal of the PEEP increment.
Methods: In 14 patients with acute lung injury (LIS score 2.7) EELV and volume-dependent dynamic compliance of the respiratory system (C_dyn,rs) were determined 45 min after removal of an additional PEEP increment (0.64 kPa added to baseline PEEP of 1.0 kPa).
Results: Nine patients kept an EELV gain of 13% (SD 7) and showed improved C_dyn,rs. In 5 patients, EELV was reduced (by 9% (SD 6)) and C_dyn,rs unchanged after removal of the PEEP increment compared to baseline.
Conclusion: A subgroup of patients with acute lung injury, the characteristics of which remain to be defined, benefit from prolonged recruitment effects up to 45 min after removal of a PEEP increment, while sequelae of continuously increased airway pressures are minimised.     

Alveolar Stability during Anaesthesia for Reconstructive Vascular Surgery in the Leg

Alveolar stability was studied during prolonged enflurane anaesthesia by using a multiple inert-gas elimination technique for the assessment of the "continuous" distribution of ventilation-perfusion ratios (_A/). All 10 patients (mean age: 61 years, six smokers) presented with increased _A/ mismatching during anaesthesia, with a redistribution of lung blood flow to regions with low or high _A/. Five patients had perfusion of units with _A/≤0.07 which may cause unstable alveoli with the presently used inspiratory gas mixture. However, only two patients displayed increasing shunting suggestive of alveolar collapse during the 3.5 h observation period. This lower than expected incidence may indicate protective mechanisms against atelectasis, such as mechanical interdependence between lung units, or collateral ventilation.     

Lung and Chest Wall Mechanics during Differential Ventilation with Selective PEEP

Eight patients free from cardio-pulmonary disease and with a mean age of 46 years were studied during general anaesthesia in the lateral position. Measurements of hemithoracic mechanics were made during four different modes of ventilation: 1. Conventional ventilation (free distribution of ventilation) with no positive end-expiratory pressure (PEEP) (CV), 2. differential ventilation (50% of ventilation to each lung) with no PEEP (DV:0), and 3 and 4. DV with selective PEEP of 0.8 and 1.6 kPa, respectively, to the dependent lung only (DV:8, DV:16). During CV, 60% of ventilation was distributed to the non-dependent lung. Non-dependent hemithoracic compliance was 64% greater and inspiratory resistance 39% lower than those of the dependent hemithorax. No significant differences between the two hemithoraces were noted during DV:0, but on application of selective PEEP the compliance of the dependent hemithorax increased and its resistance decreased. With DV:16, the compliances of the two hemithoraces were essentially equal, as were their resistances. Selective PEEP caused a larger volume increase in the dependent lung than general PEEP. Selective PEEP reduced the volume of the non-dependent lung but only by 1/3 of the simultaneous increase in that of the dependent lung. Oesophageal pressure increased only slightly on selective inflation of the dependent lung, and remained negative within the 21 volume range studied. It is suggested that the altered mechanics of the dependent lung during selective PEEP result in a more even distribution of the inspired gas within that lung.     

Differential ventilation in bilateral lung disease

General anaesthesia and many types of acute respiratory failure are accompanied by a decrease in functional residual capacity (FRC). This reduction promotes closure of dependent airways and alveolar collapse, thus impeding ventilation of these regions. Perfusion, on the other hand, is forced towards dependent regions by lowered pulmonary vascular pressure and increased alveolar pressure. Ventilation-perfusion (V/Q) inequality develops, impairing gas exchange and arterial oxygenation. Application of general positive end-expiratory pressure (PEEP) increases FRC and may improve gas exchange but cannot restore V/Q to normal. Differential ventilation, with equal distribution of ventilation between the lungs, and the application of PEEP solely to the dependent lung (selective PEEP) with the patient in the lateral position, improve V/Q matching and gas exchange with less impedance of cardiac output and less danger of barotrauma. This ventilation technique has proved successful in short-term experiments and in a small number of patients treated over several days.