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.     

Effects of sustained inflation and postinflation positive end-expiratory pressure in acute respiratory distress syndrome: focusing on pulmonary and extrapulmonary forms

OBJECTIVE: To investigate whether the response to sustained inflation and postinflation positive end-expiratory pressure varies between acute respiratory distress syndrome with pulmonary (ARDS(exp)) and extrapulmonary origin (ARDS(exp)). DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit in a university hospital. PATIENTS: A total of 11 patients with ARDS and 13 patients with ARDS. INTERVENTIONS: A 7 ml/kg tidal volume, 12-15 breaths/min respiratory rate, and an inspiratory/expiratory ratio of 1:2 was used during baseline ventilation. Positive end-expiratory pressure levels were set according to the decision of the primary physician. Sustained inflation was performed by 45 cm H2O continuous positive airway pressure for 30 secs. Postinflation positive end-expiratory pressure was titrated decrementally, starting from a level of 20 cm H2O to keep the peripheral oxygen saturation between 92% and 95%. Fio2 was decreased, and baseline tidal volume, respiratory rate, inspiratory/expiratory ratio were maintained unchanged throughout the study period. MEASUREMENTS AND MAIN RESULTS: Blood gas, airway pressure, and hemodynamic measurements were performed at the following time points: at baseline and at 15 mins, 1 hr, 4 hrs, and 6 hrs after sustained inflation. After sustained inflation, the Pao2/Fio2 ratio improved in all of the patients both in ARDS(p) and ARDS(exp). However, the Pao2/Fio2 ratio increased to >200 in four ARDS(p) patients (36%) and in seven ARDS(p) patients (54%). In two of those ARDS patients, the Pao2/Fio2 ratio was found to be <200, whereas none of the ARDS(p) patients revealed Pao2/Fio2 ratios of <200 at the 6-hr measurement. Postinflation positive end-expiratory pressure levels were set at 16.7 +/- 2.3 cm H O in ARDS(p) and 15.6 +/- 2.5 cm H2O in ARDS. The change in Pao /Fio ratios was found statistically significant in patients with ARDS(p) (p =.0001) and with ARDS(p) (p =.008). Respiratory system compliance increased in ARDS patients (p =.02), whereas the change in ARDS was not statistically significant. CONCLUSIONS: Sustained inflation followed by high levels of postinflation positive end-expiratory pressure provided an increase in respiratory system compliance in ARDS; however, arterial oxygenation improved in both ARDS forms.     

Hemodynamic and respiratory changes during lung recruitment and descending optimal positive end-expiratory pressure titration in patients with acute respiratory distress syndrome

OBJECTIVES: To investigate respiratory and hemodynamic changes during lung recruitment and descending optimal positive end-expiratory pressure (PEEP) titration. DESIGN: Prospective auto-control clinical trial. SETTING: Adult general intensive care unit in a university hospital. PATIENTS: Eighteen patients with acute respiratory distress syndrome. INTERVENTIONS: Following baseline measurements (T0), PEEP was set at 26 cm H2O and lung recruitment was performed (40/40-maneuver). Then tidal volume was set at 4 mL/kg (T26R) and PEEP was lowered by 2 cm H2O in every 4 mins. Optimal PEEP was defined at 2 cm H2O above the PEEP where Pao2 dropped by > 10%. After setting the optimal PEEP, the 40/40-maneuver was repeated and tidal volume set at 6 mL/kg (T(end)). MEASUREMENTS AND MAIN RESULTS: Arterial blood gas analysis was done every 4 mins and hemodynamic measurements every 8 mins until T(end), then in 30 (T30) and 60 (T60) mins. The Pao2 increased from T0 to T(end) (203 +/- 108 vs. 322 +/- 101 mm Hg, p < .001), but the extravascular lung water (EVLW) did not change significantly. Cardiac index (CI) and the intrathoracic blood volume (ITBV) decreased from T0 to T26R (CI, 3.90 +/- 1.04 vs. 3.62 +/- 0.91 L/min/m2, p < .05; ITBVI, 832 +/- 205 vs. 795 +/- 188 m/m2, p < .05). There was a positive correlation between CI and ITBVI (r = .699, p < .01), a negative correlation between CI and central venous pressure (r = -.294, p < .01), and no correlation between CI and mean arterial pressure (MAP). CONCLUSIONS: Following lung recruitment and descending optimal PEEP titration, the Pao2 improves significantly, without any change in the EVLW up to 1 hr. This suggests a decrease in atelectasis as a result of recruitment rather than a reduction of EVLW. There is a significant change in CI during the maneuver, but neither central venous pressure, heart rate, nor MAP can reflect these changes.     

Adapting prognostic respiratory variables of ARDS in children to small-scale community needs

PURPOSE: The clinical literature on the incidence and subsequent mortality of adult respiratory distress syndrome (ARDS) has come primarily from the experiences of large tertiary referral centers, particularly in Western Europe and North America. Consequently, very little has been published on the incidence, management, and outcome of ARDS in smaller community-based intensive care units. We aimed to delineate early clinical respiratory predictors of death in children with ARDS on the modest scale of a community hospital. MATERIALS AND METHODS: A retrospective chart review of children with ARDS needing conventional mechanical ventilation admitted to our pediatric intensive care unit from 1984 to 1997. The diagnosis of ARDS was based on acute onset of diffuse, bilateral pulmonary infiltrates of noncardiac origin and severe hypoxemia defined by partial pressure of oxygen <200 mm Hg during positive end-expiratory pressure (PEEP) of 6 cm H2O or greater for a minimum of 24 hours. Demographic, clinical, and physiological data including PaO2/ FIO2, A-aDo2, and ventilation index were retrieved. RESULTS: Fifty-six children with ARDS aged 8 +/- 5.5 years (range, 50 days to 21 years) were identified. The mortality rate was 50%. Early predictors of death included the peak inspiratory pressure (PIP), ventilation index, and PEEP on the third day after diagnosis: Nonsurvivors had significantly higher PIP (35.3 +/- 10.5 cm H2O vs 44.4 +/- 10.7 cm H2O, P < .001), PEEP (8 +/- 2.8 cm H2O vs 10.7.0 +/- 3.5 cm H2O, P < .01), and ventilation index (49.14 +/- 20.4 mm Hg x cm H2O/minute vs 61.6 +/- 51.1 mm Hg cm H2O/minute) than survivors. In contrast, PAO2/FIO2 and A-a DO2 were capable of predicting outcome by day 5 and thereafter. CONCLUSIONS: A small-scale mortality outcome for ARDS is comparable to large tertiary referral institutions. The PIP, PEEP, and ventilation index are valuable for predicting outcome in ARDS by the third day of conventional therapy. The development of a local risk profile may assist in decision-making of early application of supportive therapies in this population.     

Prone position and positive end-expiratory pressure in acute respiratory distress syndrome

OBJECTIVE: To determine whether positive end-expiratory pressure (PEEP) and prone position present a synergistic effect on oxygenation and if the effect of PEEP is related to computed tomography scan lung characteristic. DESIGN: Prospective randomized study. SETTING: French medical intensive care unit. PATIENTS: Twenty-five patients with acute respiratory distress syndrome. INTERVENTIONS: After a computed tomography scan was obtained, measurements were performed in all patients at four different PEEP levels (0, 5, 10, and 15 cm H2O) applied in random order in both supine and prone positions. MEASUREMENTS AND MAIN RESULTS: Analysis of variance showed that PEEP (p <.001) and prone position (p <.001) improved oxygenation, whereas the type of infiltrates did not influence oxygenation. PEEP and prone position presented an additive effect on oxygenation. Patients presenting diffuse infiltrates exhibited an increase of Pao2/Fio2 related to PEEP whatever the position, whereas patients presenting localized infiltrates did not have improved oxygenation status when PEEP was increased in both positions. Prone position (p <.001) and PEEP (p <.001) reduced the true pulmonary shunt. Analysis of variance showed that prone position (p <.001) and PEEP (p <.001) reduced the true pulmonary shunt. The decrease of the shunt related to PEEP was more pronounced in patients presenting diffuse infiltrates. A lower inflection point was identified in 22 patients (88%) in both supine and prone positions. There was no difference in mean lower inflection point value between the supine and the prone positions (8.8 +/- 2.7 cm H2O vs. 8.4 +/- 3.4 cm H2O, respectively). CONCLUSIONS: PEEP and prone positioning present additive effects. The prone position, not PEEP, improves oxygenation in patients with acute respiratory distress syndrome with localized infiltrates.     

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.     

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.     

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.     

Effects of recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome ventilated with high positive end-expiratory pressure

Objective: Positive end-expiratory pressure (PEEP) and recruitment maneuvers (RMs) may partially reverse atelectasis and reduce ventilation-associated lung injury. The purposes of this study were to assess a) magnitude and duration of RM effects on arterial oxygenation and on requirements for oxygenation support (Fio2/PEEP) in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) receiving ventilation with low tidal volumes and high levels of PEEP; and b) frequency of adverse respiratory and circulatory events attributable to RMs. Design: Prospective, randomized, crossover study. Setting: Thirty-four intensive care units at 19 hospitals. Patients: Seventy-two patients with early ALI/ARDS. Baseline PEEP and Fio2 were 13.8 +/- 3.0 cm H2O and 0.39 +/- 0.10, respectively (mean +/- sd). Interventions: We conducted RMs by applying continuous positive airway pressure of 35-40 cm H2O for 30 secs. We conducted sham RMs on alternate days. We monitored oxyhemoglobin saturation by pulse oximetry (SpO2), Fio2/PEEP, blood pressure, and heart rate for 8 hrs after RMs and sham RMs. We examined chest radiographs for barotrauma. Measurements and Main Results: Responses to RMs were variable. Greatest increments from baseline SpO2 within 10 mins after RMs were larger than after sham RMs (1.7 +/- 0.2 vs. 0.6 +/- 0.3 %, mean +/- SEM, p < .01). Systolic blood pressure decreased more +/- 1.1 mm Hg, p < .01). Changes in Fio2/PEEP requirements were not significantly different at any time after RMs vs. sham RMs. Barotrauma was apparent on first radiographs after one RM and one sham RM.Conclusions: In ALI/ARDS patients receiving mechanical ventilation with low tidal volumes and high PEEP, short-term effects of RMs as conducted in this study are variable. Beneficial effects on gas exchange in responders appear to be of brief duration. More information is needed to determine the role of recruitment maneuvers in the management of ALI/ARDS.     

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     

Recruitment maneuver: does it promote bacterial translocation?

OBJECTIVE: High peak airway opening pressures (Pao) are used routinely during recruitment maneuvers to open collapsed lung units. High peak Pao, however, can cause lung injury as evidenced by translocation of intratracheally inoculated bacteria. In this study we explored whether recruitment maneuvers that used high Pao could cause translocation of the intratracheally inoculated from the alveoli into the systemic circulation. DESIGN: Prospective, randomized, animal study. SETTING: Experimental animal care laboratory. SUBJECTS: Eighteen male Sprague Dawley rats.INTERVENTIONS Rats were anesthetized, tracheostomized, and ventilated with 14 cm H2O peak Pao and 0 cm H2O positive end-expiratory pressure (PEEP) in pressure-controlled ventilation (frequency, 30 bpm; inspiratory/expiratory ratio, 1:2; Fio, 1). Intratracheal inoculation of 500 microL of saline containing 1 x 10 colony forming units/mL was performed before randomization into three groups (n = 6 in each): a low-pressure group (14 cm H2O peak Pao, 0 cm H2O PEEP), a high-pressure group (45 cm H2O peak Pao, 0 cm H2O PEEP), and a recruitment maneuver group (14 cm H2O peak Pao, 0 cm H2O PEEP, and a recruitment maneuver sustained inflation of 45 cm H2O continuous positive airway pressure for 30 secs every 15 mins). Blood samples for blood gas analysis were obtained before intratracheal instillation of bacteria and at the end of the experimental protocol (2 hrs). Blood cultures were obtained before and after bacterial instillation at 30-min intervals during the experiment. Blood samples were cultured directly in sheep blood, MacConkey, and Iso-Sensitest agars and were observed on the second day. Bacteremia was defined as the presence of one or more colonies of in 1 mL of blood. MEASUREMENTS AND MAIN RESULTS: The blood cultures were positive for in only six rats in the high-pressure group and remained negative throughout the study period in the low-pressure and recruitment maneuver groups. Oxygenation deteriorated in all groups after intratracheal instillation of bacteria. In the high-pressure group, oxygenation decreased from 417 +/- 67 mm Hg to 79 +/- 20 mm Hg ( p=.004), whereas in the low-pressure and recruitment maneuver groups PaO2 decreased from 410 +/- 98 mm Hg and 383 +/- 78 mm Hg to 287 +/- 105 mm Hg ( p=.031) and 249 +/- 59 mm Hg (p =.11), respectively. CONCLUSION: Intermittent recruitment maneuvers applied as a sustained inflation superimposed on low-pressure ventilation with 0 cm H2O PEEP did not cause translocation of intratracheally inoculated.     

Repeated derecruitments accentuate lung injury during mechanical ventilation

OBJECTIVE: This study was performed to test the hypothesis that derecruitment itself might accentuate lung injury during mechanical ventilation. SETTING: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: New Zealand White rabbits (2.8-3.5 kg). INTERVENTION: Twenty-four rabbits were ventilated in pressure-controlled mode with constant tidal volume (10 mL/kg). After lung injury was induced by repeated saline lavage (PaO2 <100 torr, 13.3 kPa), a pressure-volume curve was drawn to calculate the lower inflection point (Pflex), and randomization was done. The control group (n = 8) received ventilation with positive end-expiratory pressure (PEEP) fixed at Pflex for 3 hrs. The nonderecruitment group (n = 8) was ventilated at PEEP of 2 mm Hg (2.7 cm H2O) for the initial hour and then PEEP of Pflex for the remaining 2 hrs. The derecruitment group (n = 8) was ventilated for 3 hrs with six 30-min cycles consisting of 10 mins at PEEP of 2 mm Hg (2.7 cm H2O) and 20 mins at PEEP of Pflex to induce repeated derecruitments. MEASUREMENTS AND MAIN RESULTS: Variables of gas exchange, mechanics, and hemodynamics were measured, and histologic evaluation was done. In the control group, Pao2 remained >500 torr (66.7 kPa) for 3 hrs. In the nonderecruitment group, PaO2 was 40 +/- 16 (mean +/- SD) torr (5.3 +/- 2.1 kPa) at 1 hr but increased to >500 torr (66.7 kPa) for the remaining 2 hrs after increase in PEEP to Pflex. In the derecruitment group, there was progressive decline in Pao2 with each derecruitment to 220 +/- 130 torr (29.3 +/- 17.3 kPa) at 3 hrs (p <.05 compared with other groups). Histologically there was more hyaline membrane formation in the derecruitment group compared with control (p <.05) and significantly higher mean bronchiolar injury score in the derecruitment group (1.92 +/- 0.78) than both control (0.50 +/- 0.50) and nonderecruitment (0.78 +/- 0.42) groups (p <.05). CONCLUSION: Repeated derecruitments can accentuate lung injury during mechanical ventilation.     

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.     

Alterations in regional blood flow during positive end-expiratory pressure ventilation

PEEP improves the gas-exchange abnormalities that accompany adult respiratory distress syndrome (ARDS). However, since PEEP decreases cardiac output, it may also alter regional blood flow and therefore, substrate delivery to specific organs. To test this hypothesis, radiolabeled 15-mu microspheres were used to directly quantify the effects of mechanical ventilation with PEEP on regional blood flow to individual organs in animals. Mechanical ventilation alone produced a -21.2 +/- 3.6% and a -28.1 +/- 5.2% decrease in cardiac output at 30 and 60 min, respectively. The addition of 14 cm H2O PEEP resulted in little further reduction in cardiac output at 30 and 60 min (-28 +/- 2.3% and -36.4 +/- 4.9%, respectively). However, 25 cm H2O PEEP reduced markedly (p less than .01) cardiac output (-59.2 +/- 6.1% at 30 min and -55.1 +/- 4.0% at 60 min). Although blood flows to the kidney and brain were maintained, decreases in cardiac output were invariably accompanied by proportional decreases in blood flow to the heart. Intravascular volume expansion with saline (20 ml/kg) during 14 cm H2O PEEP significantly improved cardiac output (3.23 +/- 0.34 to 4.22 +/- 0.13 L/min; p less than .01) and proportionately increased blood flow to several regional vascular beds, including the heart. These data suggest that PEEP decreases cardiac output to produce reversible alterations in blood flow to a number of regional vascular beds. These PEEP-induced alterations in regional blood flow may have important implications for the development of multiple-organ failure in ARDS patients.     

Conventional ventilation modes with small pressure amplitudes and high positive end-expiratory pressure levels optimize surfactant therapy

OBJECTIVE: High-frequency oscillation studies have shown that ventilation at high end-expiratory lung volumes combined with small volume cycles at high rates best preserves exogenous surfactant and gas exchange in lavaged lungs. We investigated whether surfactant composition and gas exchange can also be preserved by conventional modes of mechanical ventilation, which combine high levels of positive end-expiratory pressure (PEEP) with small pressure amplitudes. DESIGN: Prospective, randomized, nonblinded, controlled study. SETTING: Research laboratory. SUBJECTS: Thirty male Sprague-Dawley rats. INTERVENTIONS: Rats were lung-lavaged and treated with exogenous surfactant (100 mg/kg). After 5 mins, four different ventilator settings (F(IO)2 = 1.0) were applied for 3 hrs in four groups of rats [peak inspiratory pressure (cm H2O); static PEEP (cm H2O); inspiratory/expiratory ratio; frequency], as follows: 26/2/1:2/30 (group 26/2), 26/6/1:2/30 (group 26/6), 20/10/1:2/30 (group 20/ 10-static), and 20/6/7:3/130, creating an auto PEEP of 4 cm H2O (group 20/10-auto). MEASUREMENTS AND MAIN RESULTS: In all groups, Pao2 increased immediately to prelavage values after surfactant therapy. In group 26/2, Pao2 deteriorated to postlavage values within 30 mins when PEEP was decreased to 2 cm H2O, whereas Pao2 remained stable for 3 hrs in the other groups. The Paco2 increased in groups 26/2 and 20/10-static; Paco2 could not be reduced by increasing ventilation frequency to 130 in group 20/10-static. Groups 26/6 and 20/10-auto remained normocapnic. Bronchoalveolar lavage protein concentration was higher in groups 26/2 and 26/6 compared with groups 20/10-static and 20/10-auto. There was significantly more conversion of surface active large aggregates into nonactive small aggregates in group 26/2 compared with groups 20/10-static and 20/10-auto. CONCLUSIONS: We conclude that exogenous surfactant composition is preserved by conventional modes of mechanical ventilation that use small pressure amplitudes, and adequate oxygenation is maintained by high end-expiratory pressure levels. Effective carbon dioxide removal can be achieved by applying a ventilation mode that creates auto PEEP and not by a mode that applies the same level of PEEP by static PEEP only.     

Comparison of prone positioning and high-frequency oscillatory ventilation in patients with acute respiratory distress syndrome

OBJECTIVE: Both prone position and high-frequency oscillatory ventilation (HFOV) have the potential to facilitate lung recruitment, and their combined use could thus be synergetic on gas exchange. Keeping the lung open could also potentially be lung protective. The aim of this study was to compare physiologic and proinflammatory effects of HFOV, prone positioning, or their combination in severe acute respiratory distress syndrome (ARDS). DESIGN:: Prospective, comparative randomized study. SETTING: A medical intensive care unit. PATIENTS: Thirty-nine ARDS patients with a Pao2/Fio2 ratio <150 mm Hg at positive end-expiratory pressure > or =5 cm H2O. INTERVENTIONS: After 12 hrs on conventional lung-protective mechanical ventilation (tidal volume 6 mL/kg of ideal body weight, plateau pressure not exceeding the upper inflection point, and a maximum of 35 cm H2O; supine-CV), 39 patients were randomized to receive one of the following 12-hr periods: conventional lung-protective mechanical ventilation in prone position (prone-CV), HFOV in supine position (supine-HFOV), or HFOV in prone position (prone-HFOV). MEASUREMENTS AND MAIN RESULTS: Prone-CV (from 138 +/- 58 mm Hg to 217 +/- 110 mm Hg, p < .0001) and prone-HFOV (from 126 +/- 40 mm Hg to 227 +/- 64 mm Hg, p < 0.0001) improved the Pao2/Fio2 ratio whereas supine-HFOV did not alter the Pao2/Fio2 ratio (from 134 +/- 57 mm Hg to 138 +/- 48 mm Hg). The oxygenation index ({mean airway pressure x Fio2 x 100}/Pao2) decreased in the prone-CV and prone-HFOV groups and was lower than in the supine-HFOV group. Interleukin-8 increased significantly in the bronchoalveolar lavage fluid (BALF) in supine-HFOV and prone-HFOV groups compared with prone-CV and supine-CV. Neutrophil counts were higher in the supine-HFOV group than in the prone-CV group. CONCLUSIONS: Although HFOV in the supine position does not improve oxygenation or lung inflammation, the prone position increases oxygenation and reduces lung inflammation in ARDS patients. Prone-HFOV produced similar improvement in oxygenation like prone-CV but was associated with higher BALF indexes of inflammation. In contrast, supine-HFOV did not improve gas exchange and was associated with enhanced lung inflammation.     

Lung computed tomography during a lung recruitment maneuver in patients with acute lung injury

OBJECTIVE: To assess the acute effect of a lung recruitment maneuver (LRM) on lung morphology in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). PATIENTS: Ten patients with ALI/ARDS on mechanical ventilation. DESIGN: Prospective clinical study. SETTING: Computed tomography (CT) scan facility in a teaching hospital. INTERVENTIONS: An LRM performed by stepwise increases in positive end-expiratory pressure (PEEP) of up to 30-40 cm H(2)O. Lung basal CT sections were taken at end-expiration (patients 1 to 5), and at end-expiration and end-inspiration (patients 6 to 10). Arterial blood gases and static compliance (C(st)) were measured before, during and after the LRM. MEASUREMENTS AND MAIN RESULTS: Poorly aerated and non-aerated tissue at PEEP 10 cm H(2)O accounted for 60.0+/-29.1% of lung parenchyma, while only 1.1+/-1.8% was hyperinflated. Increasing PEEP to 20 and 30 cm H(2)O, compared to PEEP 10 cm H(2)O, decreased poorly aerated and non-aerated tissue by 16.2+/-28.0% and 33.4+/-13.8%, respectively ( p<0.05). This was associated with an increase in PaO(2) and a decrease in total static compliance. Inspiration increased alveolar recruitment at all PEEP levels. Hyperinflated tissue increased up to 2.9+/-4.0% with PEEP 30 cm H(2)O, and to a lesser degree with inspiration. No barotrauma or severe hypotension occurred. CONCLUSIONS: Lung recruitment maneuvers improve oxygenation by expanding collapsed alveoli without inducing too much hyperinflation in ALI/ARDS patients. An LRM during the CT scan gives morphologic and functional information that could be useful in setting ventilatory parameters.     

Recruitment maneuver and high positive end-expiratory pressure improve hypoxemia in patients after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism

OBJECTIVES: To investigate the effects of a recruitment maneuver and high positive end-expiratory pressure (PEEP) on oxygenation and hemodynamics in hypoxemic patients with pulmonary hypertension after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism. DESIGN: Prospective, observational, clinical study. SETTING: A surgical intensive care unit in a national heart institute. PATIENTS: Fourteen consecutively admitted patients who developed acute lung injury (Pa(O2) <300 torr at F(IO2) 1.0) and pulmonary hypertension (mean pulmonary artery pressure >25 mm Hg) after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism. INTERVENTIONS: The recruitment maneuver was an increase of PEEP to 30 cm H2O in one step for 1 min at F(IO2) 1.0. The level of pressure control ventilation during the recruitment maneuver was the same as before the maneuver. Subsequently, PEEP was decreased in 15-min intervals from 15 to 10, 5, and 0 cm H2O. MEASUREMENTS AND MAIN RESULTS: Hemodynamics and respiratory variables were analyzed before and during the recruitment maneuver and at each PEEP level. At F(IO2) 1.0, Pa(O2) increased from 240 +/- 62 torr to 470 +/- 83 torr at 15 cm H2O of PEEP and 469 +/- 75 torr at 10 cm H2O of PEEP after the recruitment maneuver (p < .001). At 15 cm H2O of PEEP, cardiac index decreased (from 2.7 +/- 0.6 at baseline to 2.2 +/- 0.3 L.min(-1).m(-2), p < .01) and mean blood pressure decreased (from 86 +/- 8 at baseline to 74 +/- 11 mm Hg, p < .05), but they returned to the baseline levels at 10 cm H2O of PEEP (2.5 +/- 0.4 L.min(-1).m(-2) and 83 +/- 9 mm Hg). There were no differences in mean pulmonary artery pressure at different levels of PEEP. CONCLUSIONS: In hypoxemic patients with pulmonary hypertension after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism, oxygenation was improved by the recruitment maneuver followed by high PEEP. However, hemodynamics were transiently suppressed and overall oxygen delivery did not change.     

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.     

Mechanical ventilation in acute respiratory failure: recruitment and high positive end-expiratory pressure are necessary

PURPOSE OF REVIEW: To review as best the critical care clinicians can recruit the acute respiratory distress syndrome (ARDS) lungs and keep the lungs opened, assuring homogeneous ventilation, and to present the experimental and clinical results of these mechanical ventilation strategies, along with possible improvements in patient outcome based on selected published medical literature from 1972 to 2004 (highlighting the period from June 2003 to June 2004 and recent results of the authors' group research). RECENT FINDINGS: In the experimental setting, repeated derecruitments accentuate lung injury during mechanical ventilation, whereas open lung concept strategies can attenuate lung injury. In the clinical setting, recruitment maneuvers improve short-term oxygenation in ARDS patients. A recent prospective clinical trial showed that low versus intermediate positive end-expiratory pressure (PEEP) levels (8 vs 13 cm H2O) associated with low tidal ventilation had the same effect on ARDS patient survival. Nevertheless, both conventional and electrical impedance thoracic tomography studies indicate that stepwise PEEP recruitment maneuvers increase lung volume and the recruitment percentage of lung tissue, and higher levels of PEEP (18-26 cm H2O) are necessary to keep the ARDS lungs opened and assure a more homogeneous low tidal ventilation. SUMMARY: Stepwise PEEP recruitment maneuvers can open collapsed ARDS lungs. Higher levels of PEEP are necessary to maintain the lungs open and assure homogenous ventilation in ARDS. In the near future, thoracic CT associated with high-performance monitoring of regional ventilation (electrical impedance tomography) may be used at the bedside to determine the optimal mechanical ventilation of ARDS patients.