Intratidal compliance-volume curve as an alternative basis to adjust positive end-expiratory pressure: a study in isolated perfused rabbit lungs

OBJECTIVE: Repeated collapse and reopening of alveoli have been shown to aggravate lung injury, which could be prevented by positive end-expiratory pressure (PEEP). Yet, how to adjust optimum PEEP is a matter of debate. We suggest a new strategy to adjust PEEP, which is based on the analysis of the intratidal compliance-volume curve. This approach was compared with a strategy based on the static pressure-volume curve. Furthermore, two other ventilator settings were investigated. One served as a negative control likely to provoke atelectasis, and the other was expected to induce overdistension. DESIGN: Prospective, randomized block design. SETTING: Laboratory. SUBJECTS: Isolated, perfused, and ventilated rabbit lungs. INTERVENTIONS: Tidal volumes of 8 mL/kg of body weight were used throughout. After stabilization, the lungs were randomized to one of four protocols (lasting 120 mins; n = 6 per group). Group 1 was ventilated at zero end-expiratory pressure. In group 2, PEEP was set above the lower inflection point of the static pressure-volume curve. In group 3, adjustment of PEEP was based on the intratidal compliance-volume curve, as determined by the slice method. In group 4, increasing PEEP levels ensured a plateau airway pressure of 20-25 cm H2O likely to provoke overdistension. MEASUREMENTS AND MAIN RESULTS: The ventilation/perfusion (VA/Q) distribution was analyzed by the multiple inert gas elimination technique. Alveolar derecruitment was indicated by shunt and low VA/Q areas as observed in group 1. In groups 2 and 3, VA/Q data initially indicated full recruitment. In contrast to group 3, shunt increased in group 2 near completion of the experiments. Group 4 showed complete recruitment, but the VA/Q distribution included high VA/Q areas. CONCLUSIONS: The intratidal compliance-volume curve represents a rational basis for adjusting PEEP in the isolated lung model. Because this strategy does not require invasive measures and facilitates continuous assessment of ventilator settings, it may be of clinical interest.     

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.     

Functional residual capacity and lung mechanics at different levels of mechanical ventilation

We assessed the effects of rapid ventilatory rates (60 to 120 breath/min) and high mechanical ventilation pressures (30/5 to 40/10 cm H2O) on lung mechanics and intravascular pressures in 9 paralyzed, sedated rabbits ventilated with a time-cycled, pressure-limited flow generator (Baby bird). Measurements of tidal volume, ventilator line pressure, tracheal pressure, functional residual capacity (FRC), and arterial and venous blood pressures showed that: 68% of the peak pressure developed by the ventilator was transmitted to the trachea at 60 breath/min, 74% at 120 breath/min, and 87% when ventilation pressures were increased to 40/10 cm H2O; when the ventilatory rate and the PEEP were increased, the end-expiratory pressure in the trachea became progressively greater than that indicated on the ventilator pressure gauge; FRC increased when the PEEP and mean tracheal pressure increased; tidal volume and dynamic compliance decreased and minute ventilation increased as ventilatory rate increased; compliance decreased whenever FRC increased, and increased whenever FRC decreased; and there was little effect on mean central venous or arterial pressure. These data indicate that increasing ventilator rates cause gas trapping within the lung. In normal animals, this may interfere with gas exchange and pulmonary blood flow. In abnormal lungs, the gas trapping may increase FRC and improve gas exchange within the lung.     

Different strategies to keep the lung open: a study in isolated perfused rabbit lungs

OBJECTIVE: Atelectatic alveoli can be recruited or kept open either by sustained inflation maneuvers or by positive end-expiratory pressure (PEEP). Little is known about potential interactions between both approaches. Especially, it is not known whether the recruiting effect of sustained inflation maneuvers is maintained in combination with a low PEEP, as suggested recently. In an attempt to answer this question, we combined sustained inflation maneuvers with either high or low PEEP. Both approaches were compared with a strategy likely to result in alveolar atelectasis and with another ensuring adequate alveolar recruitment by adjustment of PEEP alone. DESIGN: Randomized block design. SETTING: Laboratory. SUBJECTS: Isolated perfused rabbit lungs (n = 28). INTERVENTIONS: The lungs were ventilated with a tidal volume of 8 mL/kg. After stabilization, the lungs were randomized to one of four ventilatory strategies, which then were followed for 120 mins: a) PEEP 1 cm H2O (PEEP1, negative control); b) PEEP 1 cm H2O and 30 sec-sustained inflations (20 cm H2O) every 30 mins (SI-1); c) PEEP 3 cm H2O combined with sustained inflations (SI-3); and d) PEEP repeatedly adjusted following a previously established strategy ensuring full alveolar recruitment (DYN, positive control). MEASUREMENTS AND MAIN RESULTS: Distribution of ventilation and perfusion (Va/Q distribution) was analyzed by the multiple inert gas elimination technique. Volume-dependent compliance within the tidal volume was determined by using the slice method. Shunt and Va/Q mismatch significantly differed between SI-1 and SI-3, indicating full alveolar recruitment only in the latter. Data of SI-1 did not differ substantially from those of PEEP1, and data obtained in SI-3 were similar to those of DYN. CONCLUSIONS: First, enduring alveolar recruitment by sustained inflation maneuvers is only possible when the alveoli are stabilized thereafter by sufficient PEEP. Second, a ventilation strategy that uses repeated sustained inflations on a comparably high PEEP may not be superior to adequate adjustment of PEEP alone.     

呼气末正压对急性呼吸窘迫综合征肺复张容积及氧合影响的临床研究

目的　评价呼气末正压 (PEEP)对急性呼吸窘迫综合征 (ARDS)肺复张容积的影响 ,探讨ARDS患者 PEEP的选择方法。方法　以 11例血流动力学稳定、接受机械通气的 ARDS患者为研究对象 ,采用压力容积曲线法分别测定 PEEP为 5、10、15 cm H2 O(1cm H2 O=0 .0 98k Pa)时的肺复张容积 ,观察患者动脉血气、肺机械力学和血流动力学变化。结果　 PEEP分别 5、10和 15 cm H2 O时肺复张容积分别为 (4 0 .2±15 .3) ml、 (12 3.8± 4 3.1) ml和 (178.9± 4 3.5 ) m l,随着 PEEP水平的增加 ,肺复张容积亦明显增加 (P均 <0 .0 5 )。动脉氧合指数也随着 PEEP水平增加而增加 ,且其变化与肺复张容积呈正相关 (r=0 .4 83,P<0 .0 1)。不同 PEEP条件下 ,患者的肺静态顺应性无明显变化 (P>0 .0 5 )。将患者按有无低位转折点 (L IP)分为有 L IP组与无 L IP组 ,两组患者的肺复张容积都随着 PEEP水平的增加而增加 ,其中 PEEP15 cm H2 O时 L IP组患者的肺复张容积大于无 L IP组 (P<0 .0 5 )。结论　 PEEP水平越高 ,肺复张容积越大 ,肺复张容积增加与动脉氧合指数的变化呈正相关     

The effect of positive end-expiratory pressure during partial liquid ventilation in acute lung injury in piglets.

OBJECTIVES: To investigate the effects of positive end-expiratory pressure (PEEP) application during partial liquid ventilation (PLV) on gas exchange, lung mechanics, and hemodynamics in acute lung injury. DESIGN: Prospective, randomized, experimental study. SETTING: University research laboratory. SUBJECTS: Six piglets weighing 7 to 12 kg. INTERVENTIONS: After induction of anesthesia, tracheostomy, and controlled mechanical ventilation, animals were instrumented with two central venous catheters, a pulmonary artery catheter and two arterial catheters, and an ultrasonic flow probe around the pulmonary artery. Acute lung injury was induced by the infusion of oleic acid (0.08 mL/kg) and repeated lung lavage procedures with 0.9% sodium chloride (20 mL/kg). The protocol consisted of four different PEEP levels (0, 5, 10, and 15 cm H2O) randomly applied during PLV. The oxygenated and warmed perfluorocarbon liquid (30 mL/kg) was instilled into the trachea over 5 mins without changing the ventilator settings. MEASUREMENTS AND MAIN RESULTS: Airway pressures, tidal volumes, dynamic and static pulmonary compliance, mean and expiratory airway resistances, and arterial blood gases were measured. In addition, dynamic pressure/volume loops were recorded. Hemodynamic monitoring included right atrial, mean pulmonary artery, pulmonary capillary wedge, and mean systemic arterial pressures and continuous flow recording at the pulmonary artery. The infusion of oleic acid combined with two to five lung lavage procedures induced a significant reduction in PaO2/FI(O2) from 485 +/- 28 torr (64 +/- 3.6 kPa) to 68 +/- 3.2 torr (9.0 +/- 0.4 kPa) (p < .01) and in static pulmonary compliance from 1.3 +/- 0.06 to 0.67 +/- 0.04 mL/cm H2O/kg (p < .01). During PLV, PaO2/FI(O2) increased significantly from 68 +/- 3.2 torr (8.9 +/- 0.4 kPa) to >200 torr (>26 kPa) (p < .01). The highest PaO2 values were observed during PLV with PEEP of 15 cm H2O. Deadspace ventilation was lower during PLV when PEEP levels of 10 to 15 cm H2O were applied. There were no differences in hemodynamic data during PLV with PEEP levels up to 10 cm H2O. However, PEEP levels of 15 cm H2O resulted in a significant decrease in cardiac output. Dynamic pressure/volume loops showed early inspiratory pressure spikes during PLV with PEEP levels of 0 and 5 cm H2O. CONCLUSIONS: Partial liquid ventilation is a useful technique to improve oxygenation in severe acute lung injury. The application of PEEP during PLV further improves oxygenation and lung mechanics. PEEP levels of 10 cm H2O seem to be optimal to improve oxygenation and lung mechanics.     

Static and dynamic pressure-volume curves reflect different aspects of respiratory system mechanics in experimental acute respiratory distress syndrome.

INTRODUCTION: A lower inflection point, an upper inflection (or deflection) point, and respiratory system compliance can be estimated from an inspiratory static pressure-volume (SPV) curve of the respiratory system. Such data are often used to guide selection of positive end-expiratory pressure (PEEP)/tidal volume combinations. Dynamic pressure-volume (DPV) curves obtained during tidal ventilation are effortlessly displayed on modern mechanical ventilator monitors and bear a theoretical but unproven relationship to the more labor-intensive SPV curves. OBJECTIVE: Attempting to relate the SPV and DPV curves, we assessed both curves under a range of conditions in a canine oleic acid lung injury model. METHODS: Five mongrel dogs were anesthetized, paralyzed, and monitored to assure a stable preparation. Acute lung injury was induced by infusing oleic acid. SPV curves were constructed by the super-syringe method. DPV curves were constructed for a range of PEEP and inspiratory constant flow settings while ventilating at a frequency of 15 breaths/min and tidal volume of 350 mL. Functional residual capacity at PEEP = 0 cm H2O was measured by helium dilution. The change in lung volume by PEEP at 8, 16, and 24 cm H2O was measured by respiratory inductance plethysmography. RESULTS: The slope of the second portion of the DPV curve did not parallel the corresponding slope of the SPV curve. The mean lower inflection point of the SPV curve was 13.2 cm H2O, whereas the lower inflection point of the DPV curve was related to the prevailing flow and PEEP settings. The absolute lung volume during the DPV recordings exceeded (p < 0.05) that anticipated from the SPV curves by (values are mean +/- SEM) 267 +/- 86 mL, 425 +/- 129 mL, and 494 +/- 129 mL at end expiration for PEEP = 8, 16, and 24 cm H2O, respectively. CONCLUSIONS: The contours of the SPV curve are not reflected by those of the DPV curve in this model of acute lung injury. Therefore, this study indicates that DPV curve should not be used to guide the selection of PEEP/tidal volume combinations. Furthermore, an increase in end-expiratory lung volume occurs during tidal ventilation that is not reflected by the classical SPV curve, suggesting a stable component of lung volume recruitment attributable to tidal ventilation, independent of PEEP.     

Dynamic versus static respiratory mechanics in acute lung injury and acute respiratory distress syndrome

OBJECTIVES: It is not clear whether the mechanical properties of the respiratory system assessed under the dynamic condition of mechanical ventilation are equivalent to those assessed under static conditions. We hypothesized that the analyses of dynamic and static respiratory mechanics provide different information in acute respiratory failure. DESIGN: Prospective multiple-center study. SETTING: Intensive care units of eight German university hospitals. PATIENTS: A total of 28 patients with acute lung injury and acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS: Dynamic respiratory mechanics were determined during ongoing mechanical ventilation with an incremental positive end-expiratory pressure (PEEP) protocol with PEEP steps of 2 cm H2O every ten breaths. Static respiratory mechanics were determined using a low-flow inflation. MAIN RESULTS: The dynamic compliance was lower than the static compliance. The difference between dynamic and static compliance was dependent on alveolar pressure. At an alveolar pressure of 25 cm H2O, dynamic compliance was 29.8 (17.1) mL/cm H2O and static compliance was 59.6 (39.8) mL/cm H2O (median [interquartile range], p < .05). End-inspiratory volumes during the incremental PEEP trial coincided with the static pressure-volume curve, whereas end-expiratory volumes significantly exceeded the static pressure-volume curve. The differences could be attributed to PEEP-related recruitment, accounting for 40.8% (10.3%) of the total volume gain of 1964 (1449) mL during the incremental PEEP trial. Recruited volume per PEEP step increased from 6.4 (46) mL at zero end-expiratory pressure to 145 (91) mL at a PEEP of 20 cm H2O (p < .001). Dynamic compliance decreased at low alveolar pressure while recruitment simultaneously increased. Static mechanics did not allow this differentiation. The decrease in static compliance occurred at higher alveolar pressures compared with the dynamic analysis. CONCLUSIONS: Exploiting dynamic respiratory mechanics during incremental PEEP, both compliance and recruitment can be assessed simultaneously. Based on these findings, application of dynamic respiratory mechanics as a diagnostic tool in ventilated patients should be more appropriate than using static pressure-volume curves.     

Use of recruitment maneuvers and high-positive end-expiratory pressure in a patient with acute respiratory distress syndrome

OBJECTIVE: To present the use of a novel high-pressure recruitment maneuver followed by high levels of positive end-expiratory pressure in a patient with the acute respiratory distress syndrome (ARDS). DESIGN: Observations in one patient. SETTING: The medical intensive care unit at a tertiary care university teaching hospital. PATIENT: A 32-yr-old woman with severe ARDS secondary to streptococcal sepsis. INTERVENTIONS: The patient had severe gas exchange abnormalities because of acute lung injury and marked lung collapse. Attempts to optimize recruitment based on the inflation pressure-volume (PV) curve were not sufficient to avoid dependent lung collapse. We used a recruitment maneuver using 40 cm H2O of positive end-expiratory pressure (PEEP) and 20 cm H2O of pressure controlled ventilation above PEEP for 2 mins to successfully recruit the lung. The recruitment was maintained with 25 cm H2O of PEEP, which was much higher than the PEEP predicted by the lower inflection point (P(Flex)) of the PV curve. MEASUREMENTS AND MAIN RESULTS: Recruitment was assessed by improvements in oxygenation and by computed tomography of the chest. With the recruitment maneuvers, the patient had a dramatic improvement in gas exchange and we were able to demonstrate nearly complete recruitment of the lung by computed tomography. A PV curve was measured that demonstrated a P(Flex) of 16-18 cm H2O. CONCLUSION: Accumulating data suggest that the maximization and maintenance of lung recruitment may reduce lung parenchymal injury from positive pressure ventilation in ARDS. We demonstrate that in this case PEEP alone was not adequate to recruit the injured lung and that a high-pressure recruitment maneuver was required. After recruitment, high-level PEEP was needed to prevent derecruitment and this level of PEEP was not adequately predicted by the P(Flex) of the PV curve.     

Detection of ‘best’ positive end-expiratory pressure derived from electrical impedance tomography parameters during a decremental positive end-expiratory pressure trial

Introduction

This study compares different parameters derived from electrical impedance tomography (EIT) data to define ‘best’ positive end-expiratory pressure (PEEP) during a decremental PEEP trial in mechanically-ventilated patients. ‘Best’ PEEP is regarded as minimal lung collapse and overdistention in order to prevent ventilator-induced lung injury.

Methods

A decremental PEEP trial (from 15 to 0 cm H₂O PEEP in 4 steps) was performed in 12 post-cardiac surgery patients on the ICU. At each PEEP step, EIT measurements were performed and from this data the following were calculated: tidal impedance variation (TIV), regional compliance, ventilation surface area (VSA), center of ventilation (COV), regional ventilation delay (RVD index), global inhomogeneity (GI index), and intratidal gas distribution. From the latter parameter we developed the ITV index as a new homogeneity parameter. The EIT parameters were compared with dynamic compliance and the PaO₂/FiO₂ ratio.

Results

Dynamic compliance and the PaO₂/FiO₂ ratio had the highest value at 10 and 15 cm H₂O PEEP, respectively. TIV, regional compliance and VSA had a maximum value at 5 cm H₂O PEEP for the non-dependent lung region and a maximal value at 15 cm H₂O PEEP for the dependent lung region. GI index showed the lowest value at 10 cm H₂O PEEP, whereas for COV and the RVD index this was at 15 cm H₂O PEEP. The intratidal gas distribution showed an equal contribution of both lung regions at a specific PEEP level in each patient.

Conclusion

In post-cardiac surgery patients, the ITV index was comparable with dynamic compliance to indicate ‘best’ PEEP. The ITV index can visualize the PEEP level at which ventilation of the non-dependent region is diminished, indicating overdistention. Additional studies should test whether application of this specific PEEP level leads to better outcome and also confirm these results in patients with acute respiratory distress syndrome.     

Efficacy of partial liquid ventilation in improving acute lung injury induced by intratracheal acidified infant formula: determination of optimal dose and positive end-expiratory pressure level

OBJECTIVES: Partial liquid ventilation with fluorocarbon was successfully used for acute lung injury induced by oleic acid or lung lavage. Positive end-expiratory pressure (PEEP) during partial liquid ventilation enhances the efficacy of fluorocarbon. The aim of the current study was to assess whether partial liquid ventilation can repair lung damage induced by intratracheal acidified infant formula and to determine the optimal fluorocarbon dose and PEEP level. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SETTING AND SUBJECTS: Seventy-six male anesthetized rabbits. INTERVENTIONS: For study 1, acute lung injury was induced by intratracheal acidified infant formula in four groups. Next, three groups received 10, 15, or 20 mL/kg fluorocarbon, and the fourth group was conventionally gas ventilated. For study 2, acute lung injury was induced in five groups. One group was gas ventilated at a PEEP of 5 cm H2O, whereas the other four groups received fluorocarbon (15 mL/kg) and were assigned to one of four PEEP levels (5, 7.5, 10, or 12.5 cm H2O). The lungs were ventilated with 100% oxygen for 4 hrs after acute lung injury. MEASUREMENTS AND MAIN RESULTS: In study 1, fluorocarbon at doses of 15 and 20 mL/kg attenuated lung leukosequestration and edema and superoxide production of neutrophils, resulting in similar improvements in oxygenation, lung mechanics, and pathologic changes. The highest fluorocarbon dose caused mortality from pneumothorax. In study 2, the combination of PEEP with partial liquid ventilation improved gas exchange, lung compliance, pulmonary edema, and histologically observed damage. The beneficial effects of PEEP at 10 and 12.5 cm H2O were similar. Adverse side effects of 12.5 cm H2O PEEP included pneumothorax and hemodynamic instability. CONCLUSIONS: The combination of fluorocarbon and PEEP improved the physiologic, biochemical, and histologic lung injury induced by acidified infant formula. The beneficial effects of partial liquid ventilation are due, in part, to inhibition of pulmonary neutrophil accumulation and activation with fluorocarbon. The optimal fluorocarbon dose and PEEP level in our model were 15 mL/kg and 10 cm H2O, respectively.     

Partial liquid ventilation in severely surfactant-depleted, spontaneously breathing rabbits supported by proportional assist ventilation

OBJECTIVE: We hypothesized that partial liquid ventilation (PLV) would improve oxygenation in nonparalyzed, surfactant-deficient rabbits breathing spontaneously while supported by proportional assist ventilation (PAV). This ventilation mode compensates for low pulmonary compliance and high resistance and thereby facilitates spontaneous breathing. DESIGN: Randomized trial. SETTING: University animal research facility. SUBJECTS: Twenty-six anesthetized New Zealand white rabbits weighing 2592 +/- 237g (mean +/- sd). INTERVENTIONS: After pulmonary lavage (target Pao2 <100 mm Hg on mechanical ventilation with 6 cm H2O of positive end-expiratory pressure [PEEP] and an Fio2 of 1.0), rabbits were randomized to PAV (PEEP of 8 cm H2O) with or without PLV. PLV rabbits received 25 mL/kg of perfluorocarbon by intratracheal infusion (1 mL/kg/min). Pao2, Paco2, tidal volume, respiratory rate, minute ventilation, mean airway pressure, arterial blood pressure, heart rate, pulmonary compliance, and airway resistance were measured. Evaporated perfluorocarbon was refilled every 30 mins in PLV animals. After 5 hrs, animals were killed and lungs were removed. Lung injury was evaluated using a histologic score. MAIN RESULTS: Pao2 and compliance were significantly higher in PLV rabbits compared with controls (p <.05, analysis of variance for repeated measures). All other parameters were similar in both groups. CONCLUSIONS: PLV improved oxygenation and pulmonary compliance in spontaneously breathing, severely surfactant-depleted rabbits supported by PAV. The severity of lung injury by histology was unaffected.     

Partial liquid ventilation shows dose-dependent increase in oxygenation with PEEP and decreases lung injury associated with mechanical ventilation

PURPOSE: The purpose of this article is to evaluate the effect of positive end-expiratory pressure (PEEP) during partial liquid ventilation (PLV) and to investigate if lung damage associated with mechanical ventilation can be reduced by PLV. MATERIALS AND METHODS: Twenty-two New-Zealand white rabbits were ventilated in pressure-controlled mode maintaining constant tidal volume (10 mL/kg). Lung injury was induced by repeated saline lavage (PaO2 < 100 mm Hg).Two incremental PEEP steps maneuvers (IPSMs) from 2 to 10 cm H2O in 2 cm H2O steps were performed sequentially. The control group received the first IPSM in the supine position and were turned prone for the second IPSM. In the PLV group (n = 7), 12 mL/kg of perfluorodecalin was instilled after lung injury before the two IPSMs. The early prone group (n = 7) received both IPSMs in the prone position. Parameters of gas exchange, lung mechanics, and hemodynamics as well as pathology were examined. RESULTS: During the first IPSM, the PLV group showed a significant increase in PaO2 after instillation of perfluorodecalin (P < .05) and then showed a dose-dependent increase in PaO2 with PEER. The control and EP groups showed improvement in PaO2 only at higher PEEP, eventually showing no intergroup differences at PEEP of 10 cm H2O. During the second IPSM only the PLV group retained its ability to increase PaO2 to the level obtained during the first IPSM (P < .05 compared with control and EP groups). During the first IPSM all three groups showed increasing trend in static compliance (Cst) with PEEP peaking at PEEP of 8 cm H2O. During the second IPSM, only the PLV group showed increase in static compliance with PEEP (P < .05 compared with other groups). Lung histology revealed significantly less hyaline membrane formation in the PLV group (P < .05). CONCLUSION: PLV shows dose-dependent increase in oxygenation with PEEP and may reduce lung damage associated with mechanical ventilation.     

Time required for equilibration of arterial oxygen pressure after setting optimal positive end-expiratory pressure in acute respiratory distress syndrome

OBJECTIVE: To evaluate the time course of Pao2 change following the setting of optimal positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS: Twenty-five consecutive patients with ARDS. INTERVENTIONS: ARDS was diagnosed during pressure-regulated volume control ventilation with tidal volume of 7 mL/kg actual body weight, respiratory rate of 12 breaths/min, inspiratory/expiratory ratio of 1:2, Fio2 of 1, and PEEP of 5 cm H2O. A critical care attending physician obtained pressure volume curves and determined the lower inflection point. Following a rest period of 30 mins with initial ventilation variables, PEEP was set at 2 cm H2O above the lower inflection point, and serial blood samples were collected during 1-hr ventilation with optimal PEEP. Arterial blood gas analyses were performed at 1, 3, 5, 7, 9, 11, 15, 20, 30, 45, and 60 mins. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients were found eligible for the study. Three patients were excluded due to deterioration of oxygen saturation and hemodynamic instability following the initiation of optimal PEEP. Eight cases (36%) were considered to be of pulmonary origin and 14 cases (64%) of extrapulmonary origin. Optimal PEEP levels were 14 +/- 3 cm H2O and 14 +/- 4 cm H2O in pulmonary and extrapulmonary ARDS, respectively. Pao2 demonstrated a 130 +/- 101% increase at the end of 1-hr period in total study population. This improvement did not differ significantly between pulmonary and extrapulmonary forms of ARDS (135 +/- 118% vs. 127 +/- 95%, p = .8). Mean 90% oxygenation time was found to be 20 +/- 19 mins. In the subset of patients with ARDS of pulmonary origin, 90% oxygenation time was 25 +/- 26 mins, whereas it was 17 +/- 15 mins in patients with ARDS of extrapulmonary origin (p = .8). CONCLUSIONS: Our data showed that 20 mins would be adequate for obtaining a blood gas sample in ARDS patients with pulmonary and extrapulmonary origin after application of optimal PEEP 2 cm H2O above the lower inflection point.     

Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury.

OBJECTIVE: To determine the impact of different protective and nonprotective mechanical ventilation strategies on the degree of pulmonary inflammation, oxidative damage, and hemodynamic stability in a saline lavage model of acute lung injury. DESIGN: A prospective, randomized, controlled, in vivo animal laboratory study. SETTING: Animal research facility of a health sciences university. SUBJECTS: Forty-six New Zealand White rabbits. INTERVENTIONS: Mature rabbits were instrumented with a tracheostomy and vascular catheters. Lavage-injured rabbits were randomized to receive conventional ventilation with either a) low peak end-expiratory pressure (PEEP; tidal volume of 10 mL/kg, PEEP of 2 cm H2O); b) high PEEP (tidal volume of 10 mL/kg, PEEP of 10 cm H2O); c) low tidal volume with PEEP above Pflex (open lung strategy, tidal volume of 6 mL/kg, PEEP set 2 cm H2O > Pflex); or d) high-frequency oscillatory ventilation. Animals were ventilated for 4 hrs. Lung lavage fluid and tissue samples were obtained immediately after animals were killed. Lung lavage fluid was assayed for measurements of total protein, elastase activity, tumor necrosis factor-alpha, and malondialdehyde. Lung tissue homogenates were assayed for measurements of myeloperoxidase activity and malondialdehyde. The need for inotropic support was recorded. MEASUREMENTS AND MAIN RESULTS: Animals that received a lung protective strategy (open lung or high-frequency oscillatory ventilation) exhibited more favorable oxygenation and lung mechanics compared with the low PEEP and high PEEP groups. Animals ventilated by a lung protective strategy also showed attenuation of inflammation (reduced tracheal fluid protein, tracheal fluid elastase, tracheal fluid tumor necrosis factor-alpha, and pulmonary leukostasis). Animals treated with high-frequency oscillatory ventilation had attenuated oxidative injury to the lung and greater hemodynamic stability compared with the other experimental groups. CONCLUSIONS: Both lung protective strategies were associated with improved oxygenation, attenuated inflammation, and decreased lung damage. However, in this small-animal model of acute lung injury, an open lung strategy with deliberate hypercapnia was associated with significant hemodynamic instability.     

Lung recruitment during small tidal volume ventilation allows minimal positive end-expiratory pressure without augmenting lung injury.

OBJECTIVES: Ventilation with positive end-expiratory pressure (PEEP) above the inflection point (P(inf)) has been shown to reduce lung injury by recruiting previously closed alveolar regions; however, it carries the risk of hyperinflating the lungs. The present study examined the hypothesis that a new strategy of recruiting the lung with a sustained inflation (SI), followed by ventilation with small tidal volumes, would allow the maintenance of low PEEP levels ( P(inf). MEASUREMENTS AND MAIN RESULTS: In groups 2 and 4, static compliance decreased after ventilation (p < .01). Histologically, group 2 (PEEP < P(inf) without SI) showed significantly greater injury of small airways, but not of terminal respiratory units, compared with group 1. Group 3 (PEEP < P(inf) after a SI), but not group 4, showed significantly less injury of small airways and terminal respiratory units compared with group 2. CONCLUSIONS: We conclude that small tidal volume ventilation after a recruitment maneuver allows ventilation on the deflation limb of the pressure/volume curve of the lungs at a PEEP < P(inf). This strategy a) minimizes lung injury as well as, or better than, use of PEEP > P(inf), and b) ensures a lower PEEP, which may minimize the detrimental consequences of high lung volume ventilation.     

压力-容积曲线指导个体化保护性单肺通气在开胸术中的应用

目的:应用动态压力-容积曲线设定全身麻醉单肺通气时个体化的潮气量和呼气末正压(PEEP)。方法:42例ASAⅠ～Ⅱ级择期行肺叶切除术患者,常规双肺通气30min后(T0)行单肺通气,按照患者单肺通气即刻动态压力-容积曲线低位拐点对应的压力(PLIP)+0.196kPa设定PEEP值,依次按照100%、80%、60%高位拐点对应的容量(VUIP)设定潮气量,分别通气30min(T1、T2、T3)。记录各时点血流动力学和呼吸力学参数,并采集动脉和混合静脉血行血气分析,根据公式计算肺内分流率。结果:T1、T2、T3的PEEP值均为(0.64±0.13)kPa,潮气量分别为(10.1±1.2)mL/kg、(7.2±1.1)mL/kg、(5.6±0.7)mL/kg,与T1相比,T2的气道峰压、气道阻力、分流率降低;动脉氧分压、胸肺顺应性增加;T3的平均动脉压、动脉二氧化碳分压增高,差异有统计学意义(P<0.05)。结论:根据动态压力-容积曲线,80%VUIP联合PLIP+0.196kPa水平的PEEP有助于改善单肺通气氧合,降低分流,对血流动力学影响轻微。     

Intrinsic positive end-expiratory pressure in Acute Respiratory Distress Syndrome (ARDS) Network subjects

OBJECTIVE: We tested the hypothesis that subjects randomized to the 6 mL/kg predicted body weight tidal volume study group of the National Institutes of Health Acute Respiratory Distress Syndrome (ARDS) Network study had higher levels of intrinsic positive end-expiratory pressure (PEEP) than subjects randomized to the 12 mL/kg predicted body weight tidal volume study group. DESIGN: Secondary analysis of a subgroup from a randomized controlled trial. SETTING: Hospitals located in San Francisco, CA, and Seattle, WA. PATIENTS: Eighty-four patients enrolled in the ARDS Network tidal volume trial in San Francisco, CA, and Seattle, WA, with records of measurement of intrinsic PEEP. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intrinsic PEEP was assessed a median of six times over the first 48 hrs of ARDS Network protocol ventilation in study subjects, with no significant difference in number of measurements between subjects randomized to the tidal volume protocol of 6 mL/kg compared with 12 mL/kg. We found that intrinsic PEEP was higher among subjects randomized to the 6 mL/kg protocol, with a median intrinsic PEEP of 1.3 cm H2O (interquartile range, 0-3.1 cm H2O), compared with a median intrinsic PEEP of 0.5 cm H2O (interquartile range, 0-1.5 cm H2O) among subjects randomized to 12 mL/kg (p = .029). There was no difference in total PEEP between the study groups. CONCLUSIONS: In a subgroup of ARDS Network subjects, intrinsic PEEP was statistically significantly higher in subjects randomized to the 6 mL/kg protocol than those in the 12 mL/kg study group. The amount of intrinsic PEEP was very low in both study groups, and difference of median intrinsic PEEP between the groups was <1 cm H2O. It is unlikely that the difference in intrinsic PEEP between the study groups was clinically important in the ARDS Network study of low tidal volume ventilation.     

Ventilation with end-expiratory pressure in acute lung disease

In 10 patients with severe, acute respiratory failure we studied the effects of positive end-expiratory pressure when intermittent positive pressure ventilation (IPPV) with inspired oxygen (F(IO2)) up to 0.5 failed to maintain arterial oxygen tension (P(aO2)) above 70 torr.Positive end-expiratory pressures (PEEP) of 0, 5, 10, and 15 cm H(2)O were applied for 30-min periods each and in random order. Blood gas exchange, lung volumes, compliance, and hemodynamics were studied at each level of PEEP. P(aO2) (F(IO2) = 1.0) rose linearly with elevation of PEEP, the mean increase being from 152 to 347 torr, or 13 torr/cm H(2)O PEEP. Mean functional residual capacity (FRC) was 1.48+/-0.78 liters at zero PEEP (i.e., IPPV) and the increase was essentially linear, reaching 2.37 liters at 15 cm H(2)O PEEP. P(aO2) and FRC showed a close correlation. Total and lung static compliance were greater during ventilation with high than with low levels of PEEP. The increase in P(aO2) correlated with the specific lung compliance. Dynamic lung compliance decreased progressively with rising levels of PEEP except for an increase with 5 and 10 cm H(2)O PEEP in patients with initial values of 0.06 liter/cm H(2)O or higher. Cardiac index fell in some patients and rose in others and there was no correlation of mean cardiac index, systemic blood pressure, or peripheral vascular resistance with level of PEEP. The most probable explanation for the effect of PEEP on P(aO2) and compliance is recruitment of gas exchange airspaces and prevention of terminal airway closure.     

Effects of ventilatory pattern on experimental lung injury caused by high airway pressure

OBJECTIVE: To determine the influence of clinician-adjustable ventilator settings on the development of ventilator-induced lung injury, as assessed by changes in gas exchange (Pao2), compliance, functional residual capacity, and wet weight to dry weight ratio. DESIGN: Randomized in vivo rabbit study. SETTING: Hospital research laboratory. SUBJECTS: Forty-four anesthetized, mechanically ventilated adult rabbits. INTERVENTIONS: Ventilation for 2 hrs with pressure control ventilation at 45 cm H2O, Fio2 = 0.6, and randomization to one of five ventilatory strategies using combinations of positive end-expiratory pressure (3 or 12 cm H2O), inspiratory time (0.45, 1.0, or 2.0 secs), and frequency (9 or 23/min). MEASUREMENTS AND MAIN RESULTS: Among the ventilator strategies applied, PEEP at 12 cm H2O (elevated positive end-expiratory pressure) and inspiratory time at 0.45 secs (reduced inspiratory time) best preserved Pao2 (p <.003) and compliance (p <.035). During injury development, two consistent changes were observed: Tidal volume increased, and airway pressure waveform was transformed by extending the time to attain target pressure. CONCLUSIONS: In this preclinical model, lung injury was attenuated by decreasing inspiratory time. As lung injury occurred, tidal volume increased and airway pressure waveform changed.