A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial

OBJECTIVE: It has been shown in a two-center study that high positive end-expiratory pressure (PEEP) and low tidal volume (LTV) improved outcome in ARDS. However, that study involved patients with underlying diseases unique to the study area, was conducted at only two centers, and enrolled a small number of patients. We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system (Pflex) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome (ARDS). DESIGN: Randomized, controlled clinical trial. SETTING: Network of eight Spanish multidisciplinary intensive care units (ICUs) under the acronym of ARIES (Acute Respiratory Insufficiency: Espa?a Study). PATIENTS: All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study. If 24 hrs after meeting ARDS criteria, the Pao2/Fio2 remained < or =200 mm Hg on standard ventilator settings, patients were randomized into two groups: control and Pflex/LTV. INTERVENTIONS: In the control group, tidal volume was 9-11 mL/kg of predicted body weight (PBW) and PEEP > or =5 cm H2O. In the Pflex/LTV group, tidal volume was 5-8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O. In both groups, Fio2 was set to maintain arterial oxygen saturation >90% and Pao2 70-100 mm Hg, and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg. MEASUREMENTS AND MAIN RESULTS: The study was stopped early based on an efficacy stopping rule as described in the methods. Of 103 patients who were enrolled (50 control and 53 Pflex), eight patients (five in control, three in Pflex) were excluded from the final evaluation because the random group assignment was not performed in one center according to protocol. Main outcome measures were ICU and hospital mortality, ventilator-free days, and nonpulmonary organ dysfunction. ICU mortality (24 of 45 [53.3%] vs. 16 of 50 [32%], p = .040), hospital mortality (25 of 45 [55.5%] vs. 17 of 50 [34%], p = .041), and ventilator-free days at day 28 (6.02 +/- 7.95 in control and 10.90 +/- 9.45 in Pflex/LTV, p = .008) all favored Pflex/LTV. The mean difference in the number of additional organ failures postrandomization was higher in the control group (p < .001). CONCLUSIONS: A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS.     

Respective effects of end-expiratory and end-inspiratory pressures on alveolar recruitment in acute lung injury

OBJECTIVE: A low tidal volume can induce alveolar derecruitment in patients with acute lung injury. This study was undertaken to evaluate whether this resulted mainly from the decrease in tidal volume or from the reduction in end-inspiratory plateau pressure and whether there is any benefit in raising the level of positive end-expiratory pressure (PEEP) while plateau pressure is kept constant. DESIGN: Prospective crossover study. SETTING: Medical intensive care unit of a university teaching hospital. PATIENTS: Fifteen adult patients ventilated for acute lung injury (PaO2/FiO2, 158 +/- 34 mm Hg; lung injury score, 2.7 +/- 0.6). INTERVENTIONS: Three combinations were tested: PEEP at the lower inflection point with 6 mL/kg tidal volume, PEEP at the lower inflection point with 10 mL/kg tidal volume, and high PEEP with tidal volume at 6 mL/kg, keeping the plateau pressure similar to the preceding condition. MEASUREMENTS AND MAIN RESULTS: Pressure-volume curves at zero PEEP and at set PEEP were recorded, and recruitment was calculated as the volume difference between both curves for pressures ranging from 15 to 30 cm H2O. Arterial blood gases were measured for all patients. For a similar PEEP at the lower inflection point (10 +/- 3 cm H2O), tidal volume reduction (10 to 6 mL/kg) led to a significant derecruitment. A low tidal volume (6 mL/kg) with high PEEP (14 +/- 3 cm H2O), however, induced a significantly greater recruitment and a higher Pao than the two other strategies. CONCLUSION: At a given plateau pressure (i.e., similar end-inspiratory distension), lowering tidal volume and increasing PEEP increase recruitment and PaO2.     

Effects of positive end-expiratory pressure on gas exchange and expiratory flow limitation in adult respiratory distress syndrome

OBJECTIVE: To assess the effects of different positive end-expiratory pressure (PEEP) levels (0, 5, 10, and 15 cm H2O) on tidal expiratory flow limitation (FL), regional intrinsic positive end-expiratory pressure (PEEPi) inhomogeneity, alveolar recruited volume (Vrec), respiratory mechanics, and arterial blood gases in mechanically ventilated patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS: Thirteen sedated, mechanically ventilated patients during the first 2 days of ARDS. INTERVENTIONS: Detection of tidal FL and evaluation of total dynamic PEEP (PEEPt,dyn), total static PEEP (PEEPt,st), respiratory mechanics, and Vrec from pressure, flow, and volume traces provided by the ventilator. The average (+/-sd) tidal volume was 7.1 +/- 1.5 mL/kg, the total cycle duration was 2.9 +/- 0.45 secs, and the duty cycle was 0.35 +/- 0.05. MEASUREMENTS: Tidal FL was assessed using the negative expiratory pressure technique. Regional PEEPi inhomogeneity was assessed as the ratio of PEEPt,dyn to PEEPt,st (PEEPi inequality index), and Vrec was quantified as the difference in lung volume at the same airway pressure between quasi-static inflation volume-pressure curves on zero end-expiratory pressure (ZEEP) and PEEP. RESULTS: On ZEEP, seven patients exhibited FL amounting to 31 +/- 8% of tidal volume. They had higher PEEPt,st and PEEPi,st ( p<.001) and lower PEEPi inequality index ( p<.001) than the six nonflow-limited (NFL) patients. Two FL patients became NFL with PEEP of 5 cm H2O and five with PEEP of 10 cm H2O. In both groups, PaO2 increased progressively with PEEP. In the FL group, there was a significant correlation of PaO2 to PEEPi inequality index ( p=.002). For a given PEEP, Vrec was greater in NFL than FL patients, and a significant correlation of Pao to Vrec ( p<.001) was found only in the NFL group. CONCLUSIONS: We conclude that on ZEEP, tidal FL is common in ARDS patients and is associated with greater regional PEEPi inhomogeneity than in NFL patients. With PEEP of 10 cm H2O, flow limitation with concurrent cyclic dynamic airway compression and re-expansion and the risk of "low lung volume injury" were absent in all patients. In FL patients, PEEP induced a significant increase in PaO2, mainly because of the reduction of regional PEEPi inequality, whereas in the NFL group, arterial oxygenation was improved satisfactorily because of alveolar recruitment.     

Lung collapse during low tidal volume ventilation in acute respiratory distress syndrome

BACKGROUND: Current ventilator management for acute respiratory distress syndrome (ARDS) incorporates low tidal volume (V(T)) ventilation in order to limit ventilator-induced lung injury. Low V(T) ventilation in supine patients, without the use of intermittent hyperinflations, may cause small airway closure, progressive atelectasis, and secretion retention. Use of high positive end-expiratory pressure (PEEP) levels with low V(T) ventilation may not counter this effect, because regional differences in intra-abdominal hydrostatic pressure may diminish the volume-stabilizing effects of PEEP. CASE SUMMARY: A 35-year-old man with abdominal compartment syndrome (intra-abdominal pressure > 48 cm H2O developed ARDS and was treated with V(T) of 4.5 mL/kg and PEEP of 20 cm H2O. Despite aggressive fluid therapy, appropriate airway humidification and tracheal suctioning, the patient developed complete bronchial obstruction, involving the entire right lung and left upper lobe. After bronchoscopy the patient was placed on a higher V(T) (7.0 mL/kg). Intermittent PEEP was instituted at 30 cm H2O for 2 breaths every 3 minutes. This intermittently raised the end-inspiratory plateau pressure from 38 cm H2O to 50 cm H2O. With the same airway humidity and tracheal suctioning practices bronchial obstruction did not reoccur. CONCLUSION: Low V(T) ventilation in ARDS may increase the risk of small airway closure and retained secretions. This adverse effect highlights the importance of pulmonary hygiene measures in ARDS during lung-protective ventilation.     

Clinical implementation of the ARDS network protocol is associated with reduced hospital mortality compared with historical controls

OBJECTIVE: To assess the impact of implementing a low tidal volume ventilation strategy on hospital mortality for patients with acute lung injury or acute respiratory distress syndrome. DESIGN: Retrospective, uncontrolled study. SETTING: Adult medical-surgical and trauma intensive care units at a major inner city, university-affiliated hospital. PATIENTS: A total of 292 patients with acute lung injury or acute respiratory distress syndrome. INTERVENTIONS: Between the years 2000 and 2003, 200 prospectively identified patients with acute lung injury/acute respiratory distress syndrome were managed by the ARDS Network low tidal volume protocol. A historical control group of 92 acute respiratory distress syndrome patients managed by routine practice from 1998 to 1999 was used for comparison. MEASUREMENTS AND MAIN RESULTS: Patients managed with the ARDS Network protocol had a lower hospital mortality compared with historical controls (32% vs. 51%, respectively; p = .004). Multivariate logistic regression estimated an odds ratio of 0.32 (95% CI, 0.17-0.59; p = .0003) for mortality risk with use of the ARDS Network protocol. Protocol-managed patients had a lower tidal volume (6.2 +/- 1.1 vs. 9.8 +/- 1.5 mL/kg; p < .0001) and plateau pressure (27.5 +/- 6.4 vs. 33.8 +/- 8.9 cm H2O; p < .0001) than historical controls. CONCLUSION: Adoption of the ARDS Network protocol for routine ventilator management of acute lung injury/acute respiratory distress syndrome patients was associated with a lower mortality compared with recent historical controls.     

Effect of alveolar recruitment maneuver in early acute respiratory distress syndrome according to antiderecruitment strategy,etiological category of diffuse lung injury,and body position of the patient

OBJECTIVE: To assess how the level of positive end-expiratory pressure (PEEP) (antiderecruitment strategy), etiological category of diffuse lung injury, and body position of the patient modify the effect of the alveolar recruitment maneuver (ARM) in acute respiratory distress syndrome (ARDS). DESIGN: Prospective clinical trial. SETTING: Medical intensive care unit at a tertiary hospital. PATIENTS: Forty-seven patients with early ARDS, including 19 patients from our preliminary study. INTERVENTION: From baseline ventilation at a tidal volume of 8 mL/kg and PEEP of 10 cm H2O, the ARM (a stepwise increase in the level of PEEP up to 30 cm H2O with a concomitant decrease in the magnitude of tidal volume down to 2 mL/kg) was given with (ARM + PEEP, n = 20) or without (ARM only, n = 19) subsequent increase of PEEP to 15 cm H2O. In eight other patients, PEEP was increased to 15 cm H2O without a preceding ARM (PEEP only). MEASUREMENTS AND RESULTS: In all three groups, Pao2 was increased by the respective intervention (all p<.05). In the ARM-only group, Pao2 at 15 mins after intervention was lower than Pao2 immediate after intervention (p =.046). In the ARM + PEEP group, no such decrease in Pao2 was observed, and Pao2 at 15, 30, 45, and 60 mins after intervention was higher than in the ARM-only group (all p<.05). Compared with the PEEP-only group, Pao2 of the ARM + PEEP group was higher immediately after intervention and at the later time points (all p <.05). Compared with patients with ARDS associated with direct lung injury (pulmonary ARDS), patients with ARDS associated with indirect lung injury (extrapulmonary ARDS) showed a greater increase in Pao2 (27 +/- 21% vs. 130 +/- 112%; p=.002) and a greater decrease in radiologic scores (1.0 +/- 2.4 vs. 3.4 +/- 1.5; p=.005) after the ARM. The increase in Pao2 induced by the ARM was greater for patients in the supine position than for patients in the prone position (61 +/- 82% vs. 21 +/- 14%; p=.028). Consequently, Pao immediately after the ARM was similar in the two groups of patients in different positions. CONCLUSIONS: After the ARM, a sufficient level of PEEP is required as an antiderecruitment strategy. Pulmonary ARDS and extrapulmonary ARDS may be different pathophysiologic entities. An effective ARM may obviate the need for the prone position in ARDS at least in terms of oxygenation.     

Experimental results of using the "open lung concept"

Several elements of the "open lung concept", like ventilation with small tidal volumes, were incorporated into various ventilatory strategies. Our study demonstrates how the whole concept can be applied in an animal model using a standardized protocol with the following possible results. Eighteen pigs weighing between 30 and 45 kg were anaesthetized, tracheotomized and ventilated. Acute lung injury was induced by surfactant washout. Blood gases were monitored via a continuous arterial sensor system (Trendcare system). After washout, the ventilatory pattern of the American "ARDS Network study" was applied (PEEP = 9 cmH2O, volume controlled mode with a tidal volume of 6 ml/kg body weight and a respiratory rate of 25 breaths per minute). Afterwards, the opening pressure and the pressure at which the lung collapses were titrated. Both levels were used as the basis for adjusting the recruitment pressure and PEEP, which was necessary to keep the lung open. The respiratory rate was chosen in such a way that at a low intrapulmonary pressure difference between inspiration and expiration as well as normocapnia was reached. After induction of an acute lung injury by surfactant washout, the oxygenation index (OI) dropped from 556 +/- 54 to 176 +/- 89 mmHg. In the "ARDS Network" mode, OI increased to 285 +/- 49 mmHg. After alveolar recruitment with a peak pressure of 53 +/- 7 cmH2O and application of a median PEEP of 17 +/- 3 cmH2O, oxygenation returned close to baseline. A pCO2 of 33 +/- 4 mmHg resulted after using a respiratory rate of 39 breaths per minute. The median tidal volume was 8 ml/kg body weight. Despite a short arterial systolic blood pressure drop of 23 +/- 11 mmHg during recruitment, no significant difference was detectable afterwards compared to the baseline. Using low tidal volumes alone, complete reopening was not achieved in an experimentally induced acute lung injury. After recruitment manoeuvres, it was possible to reopen the lung and keep it open by application of a sufficient PEEP.     

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     

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.     

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.     

Volume-dependent compliance and ventilation-perfusion mismatch in surfactant-depleted isolated rabbit lungs

OBJECTIVE: Volume-dependent alterations of lung compliance are usually studied over a very large volume range. However, the course of compliance within the comparably small tidal volume (intratidal compliance-volume curve) may also provide relevant information about the impact of mechanical ventilation on pulmonary gas exchange. Consequently, we determined the association of the distribution of ventilation and perfusion with the intratidal compliance-volume curve after modification of positive end-expiratory pressure (PEEP). DESIGN: Repeated measurements in randomized order. SETTING: An animal laboratory. SUBJECTS: Isolated perfused rabbit lungs (n = 14). INTERVENTIONS: Surfactant was removed by bronchoalveolar lavage. The lungs were ventilated thereafter with a constant tidal volume (10 mL/kg body weight). Five levels of PEEP (0-4 cm H2O) were applied in random order for 20 mins each. MEASUREMENTS AND MAIN RESULTS: The intratidal compliance-volume curve was determined with the slice method for each PEEP level. Concurrently, pulmonary gas exchange was assessed by the multiple inert gas elimination technique. At a PEEP of 0-1 cm H2O, the intratidal compliance-volume curve was formed a bow with downward concavity. At a PEEP of 2 cm H2O, concavity was minimal or compliance was almost constant, whereas higher PEEP levels (3-4 cm H2O) resulted in a decrease of compliance within tidal inflation. Pulmonary gas exchange did not differ between PEEP levels of of 0, 1, and 2 cm H2O. Pulmonary shunt was lowest and perfusion of alveoli with a normal ventilation-perfusion was highest at a PEEP of 3-4 cm H2O. Deadspace ventilation did not change significantly but tended to increase with PEEP. CONCLUSIONS: An increase of compliance at the very beginning of tidal inflation was associated with impaired pulmonary gas exchange, indicating insufficient alveolar recruitment by the PEEP level. Consequently, the lowest PEEP level preventing alveolar atelectasis could be detected by analyzing the course of compliance within tidal volume without the need for total lung inflation.     

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.     

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

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

Acute effects of tidal volume strategy on hemodynamics, fluid balance, and sedation in acute lung injury

OBJECTIVE: To examine the effects of mechanical ventilation with a tidal volume of 6 mL/kg compared with 12 mL/kg predicted body weight on hemodynamics, vasopressor use, fluid balance, diuretics, sedation, and neuromuscular blockade within 48 hrs in patients with acute lung injury and acute respiratory distress syndrome. DESIGN: Retrospective analysis of a previously conducted randomized, clinical trial. SETTING: Two adult intensive care units at a tertiary university medical center and a large county hospital. PATIENTS: One hundred eleven patients who were enrolled in the National Institutes of Health ARDS Network trial at the University of California, San Francisco. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compared with 12 mL/kg predicted body weight, treatment with a tidal volume of 6 mL/kg predicted body weight had no adverse effects on hemodynamics. There were also no differences in the need for supportive therapies, including vasopressors, intravenous fluids, or diuretics. In addition, there were no differences in body weight, urine output, and fluid balance. Finally, there was no difference in the need for sedation or neuromuscular blockade between the two tidal volume protocols. CONCLUSIONS: When compared with ventilation with 12 mL/kg predicted body weight, patients treated with the lung-protective 6 mL/kg predicted body weight tidal volume protocol had no difference in their supportive care requirements. Therefore, concerns regarding potential adverse effects of this protocol should not preclude its use in patients with acute lung injury or the acute respiratory distress syndrome.     

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

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

Alveolar recruitment in combination with sufficient positive end-expiratory pressure increases oxygenation and lung aeration in patients with severe chest trauma

OBJECTIVE: Investigation of oxygenation and lung aeration during mechanical ventilation according to the open lung concept in patients with acute lung injury or acute respiratory distress syndrome. DESIGN: Retrospective analysis. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: We retrospectively identified 17 patients with acute lung injury/acute respiratory distress syndrome due to pulmonary contusion who had thoracic helical computed tomography scans before and after ventilation with the open lung concept. INTERVENTIONS: Baseline ventilation consisted of low tidal volumes (< or =6 mL/kg) and positive end-expiratory pressure (PEEP; 5-17 cm H2O). We briefly applied high inspiratory pressures for opening up collapsed alveoli. External PEEP and intrinsic PEEP were combined to keep recruited lung units open. We generated intrinsic PEEP by pressure-cycled high-frequency inverse ratio ventilation (80 min, inspiratory/expiratory ratio 2:1) and maintained our ventilatory strategy for 24 hrs. Then, after reducing total PEEP by decreasing respiratory rate, Pao2/Fio2 ratio was reevaluated. If it remained >300 mm Hg, weaning was started. If not, previous ventilator settings were resumed for another 24 hrs after recruiting the lungs once again. MEASUREMENTS AND MAIN RESULTS: Physiologic variables and ventilator settings were obtained from routine charts. Data from computed tomography before and after the open lung concept were analyzed for volumetric quantification of lung aeration and collapse. All results are presented as median and range. During baseline ventilation, PEEP was 10 (range, 5-17) cm H2O and after recruitment 21 (range, 18-26) cm H2O. Opening pressures were 65 (range, 50-80) cm H2O. After recruitment, Pao2/Fio2 ratio was higher in all patients. Total lung volume increased from 2915 (range, 1952-4941) to 4247 (range, 2285-6355) mL and normally aerated volume from 1742 (range, 774-2941) to 2971 (range, 1270-5232) mL. Atelectasis decreased significantly from 604 (range, 147-1538) to 106 (range, 0-736) mL. Hyperinflation increased significantly from 5 (range, 0-188) to 62 (range, 1-424) mL, whereas poor aeration did not change substantially from 649 (range, 302-1292) to 757 (range, 350-1613) mL. No hemodynamic problems occurred. CONCLUSIONS: Lung recruitment increased arterial oxygenation, normally aerated lung volume, and total lung volume while decreasing the amount of collapsed tissue. These results indicate that the open lung concept is a reasonable mode of ventilation for patients with severe chest trauma.     

Approaches to conventional mechanical ventilation of the patient with acute respiratory distress syndrome

To minimize ventilator-induced lung injury, attention should be directed toward avoidance of alveolar over-distention and cyclical opening and closure of alveoli. The most impressive study of mechanical ventilation to date is the Acute Respiratory Distress Syndrome (ARDS) Network study of higher versus lower tidal volume (V(T)), which reported a reduction in mortality from 39.8% to 31.0% with 6 mL/kg ideal body weight rather than 12 mL/kg ideal body weight (number-needed-to-treat of 12 patients). To achieve optimal lung protection, the lowest plateau pressure and V(T) possible should be selected. What is most important is limitation of V(T) and alveolar distending pressure, regardless of the mode set on the ventilator. Accumulating observational evidence suggests that V(T) should be limited in all mechanically ventilated patients-even those who do not have ALI/ARDS. Evidence does not support the use of pressure controlled inverse-ratio ventilation. Although zero PEEP is probably injurious, an area of considerable controversy is the optimal setting of PEEP. Available evidence does not support the use of higher PEEP, compared to lower PEEP, in unselected patients with acute lung injury (ALI)/ARDS. However, results of a meta-analysis using individual patients from 3 randomized controlled trials suggest that higher PEEP should be used for ARDS, whereas lower PEEP may be more appropriate in patients with ALI. PEEP should be set to maximize alveolar recruitment while avoiding over-distention. Many approaches for setting PEEP have been described, but evidence is lacking that any one approach is superior to any other. In most, if not all, cases of ALI/ARDS, conventional ventilation strategies can be used effectively to provide lung-protective ventilation strategies.     

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.     

Setting the frequency-tidal volume pattern

Alveolar (and thus arterial) P(O2) and P(CO2) clearly depend on minute ventilation. However, we need to balance gas exchange goals against the risk of overstretching, especially of the healthier regions of the lung. The plateau pressure is probably the best easily-obtained marker of the risk of stretch in the lung, and a commonly quoted threshold is 30--35 cm H(2)O, the normal maximum transalveolar pressure at total lung capacity. In establishing the proper balance of stretch versus gas exchange, we need to address what levels of pH and P(aO2) we consider acceptable. There are no good data to guide us on the lowest tolerable pH, but 7.2 is commonly quoted in the literature, and 7.15 was the lower limit of acceptability in the ARDS (acute respiratory distress syndrome) Network trial. P(O2) levels as low as 55 mm Hg may be well tolerated, provided there is reasonable oxygen delivery. In distributing the desired minute volume between respiratory frequency and tidal volume (V(T)), a V(T) of 6 mL/kg ideal body weight has been shown to improve ARDS outcome, compared to 12 mL/kg. Thus, 6 mL/kg should be the "start point." Adjustments upward could be considered the plateau pressure is acceptable, in order to improve gas exchange or comfort. Conversely, downward adjustments should be considered if the plateau pressure is high and the gas exchange is acceptable. Frequency is adjusted for the desired minute ventilation. It must be recognized, however, that as frequency (and minute ventilation) increases, the risk of air trapping and intrinsic positive end-expiratory pressure (PEEP) increases. Just like applied PEEP, intrinsic PEEP increases the baseline pressure and stretch upon which the V(T) is delivered. The end-inspiratory stretch increases accordingly. The shape and duration of the flow pattern may affect gas mixing, recruitment, cardiac function, intrinsic PEEP buildup, and patient comfort. It is also conceivable that certain flow patterns can produce an acceleration injury. Although small clinical trials using physiologic end points espouse certain flow patterns, there are no good outcome data at present supporting any particular approach. Some authors suggest that high-frequency ventilation (HFV) might be considered an "ultimate" lung-protective strategy. HFV creates considerable intrinsic PEEP, which, when coupled with sustained inflation maneuvers, can provide substantial alveolar recruitment. In addition, the small V(T) of HFV prevents excessive end-inspiratory distention. Although considerable clinical data support the use of HFV in pediatric patients at risk for ventilator-induced lung injury, there are few data from adults. Whether HFV will prove valuable in well-designed open lung strategies in the adult population still has to be determined.     

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.