Background In patients with the acute respiratory distress syndrome,massive alveolar collapse and cyclic lung reopening and overdistentionduring mechanical ventilation may perpetuate alveolar injury.We determined whether a ventilatory strategy designed to minimizesuch lung injuries could reduce not only pulmonary complicationsbut also mortality at 28 days in patients with the acute respiratorydistress syndrome.
Methods We randomly assigned 53 patients with early acute respiratorydistress syndrome (including 28 described previously), all ofwhom were receiving identical hemodynamic and general support,to conventional or protective mechanical ventilation. Conventionalventilation was based on the strategy of maintaining the lowestpositive end-expiratory pressure (PEEP) for acceptable oxygenation,with a tidal volume of 12 ml per kilogram of body weight andnormal arterial carbon dioxide levels (35 to 38 mm Hg). Protectiveventilation involved end-expiratory pressures above the lowerinflection point on the static pressure–volume curve,a tidal volume of less than 6 ml per kilogram, driving pressuresof less than 20 cm of water above the PEEP value, permissivehypercapnia, and preferential use of pressure-limited ventilatorymodes.
Results After 28 days, 11 of 29 patients (38 percent) in theprotective-ventilation group had died, as compared with 17 of24 (71 percent) in the conventional-ventilation group (P<0.001).The rates of weaning from mechanical ventilation were 66 percentin the protective-ventilation group and 29 percent in the conventional-ventilationgroup (P = 0.005); the rates of clinical barotrauma were 7 percentand 42 percent, respectively (P = 0.02), despite the use ofhigher PEEP and mean airway pressures in the protective-ventilationgroup. The difference in survival to hospital discharge wasnot significant; 13 of 29 patients (45 percent) in the protective-ventilationgroup died in the hospital, as compared with 17 of 24 in theconventional-ventilation group (71 percent, P = 0.37).
Conclusions As compared with conventional ventilation, the protectivestrategy was associated with improved survival at 28 days, ahigher rate of weaning from mechanical ventilation, and a lowerrate of barotrauma in patients with the acute respiratory distresssyndrome. Protective ventilation was not associated with a higherrate of survival to hospital discharge.
Mechanical ventilation can damage the lungs.1,2 Lesions at thealveolar–capillary interface,3 alterations in permeability,4and edema5,6,7 have repeatedly been shown to occur in animalssubjected to adverse patterns of mechanical ventilation.
In clinical practice, however, the "mechanical stretch" causedby conventional ventilation has been found to be detrimentalin only a few uncontrolled studies.8,9,10,11 Large variationsin the susceptibility of individual animal species12 and theapparent success of mechanical ventilation based on a strategyof using the lowest positive end-expiratory pressure (PEEP)that results in acceptable oxygenation13,14 suggest that thedevastating effects observed in animals cannot be easily extrapolatedto humans.
We recently demonstrated that mechanical lung protection canbe provided in patients with the acute respiratory distresssyndrome, resulting in better pulmonary function and higherrates of weaning from the ventilator.15 Briefly, lung protectionwas based on a strategy of maintaining low inspiratory drivingpressures (<20 cm of water above PEEP, with low tidal volumesand preferential use of limited airway pressure over regulationof arterial carbon dioxide levels), with the simultaneous circumventionof alveolar collapse through the use of high PEEP to keep end-expiratorypressures above the lower inflection point (PFLEX) on the staticpressure–volume curve of the respiratory system. The nearlymaximal alveolar recruitment and aeration accomplished withthis strategy were intended to minimize shear stresses in thelung tissue during inspiration.15
We have extended our earlier report15 and evaluated the effectof mechanical lung protection on survival. We hypothesized thatpreventing the persistent collapse of recruitable units (alveolarunits anatomically preserved but requiring high opening pressuresfor aeration) and reducing cyclic lung reopening and stretchduring mechanical breaths would result in lower rates of pulmonarycomplications and mortality at 28 days in patients with theacute respiratory distress syndrome.
Methods
Study Population
Between December 1990 and July 1995, 53 patients with the acuterespiratory distress syndrome were prospectively enrolled inthe trial (including 28 described previously15). The hemodynamicdata in 48 of the patients during the first seven days of thestudy have been reported elsewhere.16 The study was conductedin two intensive care units in Brazil: one in São Pauloand one in Porto Alegre. The protocol was approved by the hospitals'medical-ethics committees, and informed consent was obtainedfrom each patient or the patient's next of kin.
Each year during the study period, a total of about 60 patientswith the acute respiratory distress syndrome were admitted tothe two intensive care units. The criteria for enrollment werean underlying disease process known to be associated with theacute respiratory distress syndrome along with a lung-injuryscore17 of 2.5 or higher (range, 0 [normal] to 4 [most severe])plus a pulmonary arterial wedge pressure of less than 16 mmHg. Confirmation that the tip of the pulmonary arterial catheterwas in the area of the lung zone where capillary vessels werepatent, transmitting left atrial pressures backward, was assessedwith two mechanical maneuvers.5,18 The exclusion criteria (listedin decreasing order of frequency) were previous lung or neuromusculardisease, mechanical ventilation for more than one week, uncontrolledterminal disease, previous barotrauma (pneumothorax, pneumomediastinum,or subcutaneous emphysema), previous lung biopsy or resection,an age of more than 70 years or less than 14 years, uncontrollableand progressive acidosis, signs of intracranial hypertension,and documented coronary insufficiency. The primary diagnosesat enrollment are shown in Table 1.
Table 1. Base-Line Characteristics of the Study Groups.
Stabilizing Procedures and Randomization
After enrollment, all patients underwent a standardized regimenof ventilatory–hemodynamic procedures for at least 30minutes (control period), during which time their initial clinicalcondition was evaluated and stabilized. This regimen consistedof volume-controlled ventilation (tidal volume, 10 ml per kilogramof body weight), a square-wave inspiratory flow of 50 litersper minute, a respiratory rate of 15 cycles per minute, an inspiratorypause of 0.4 second, an inspiratory oxygen fraction of 1.0,PEEP of 5 cm of water or the minimal value necessary to maintainan arterial oxygen saturation of more than 85 percent, 5 percentalbumin administered intravenously until the pulmonary arterialwedge pressure was higher than 9 mm Hg, dobutamine administeredintravenously in a fixed dose of 5 µg per kilogram perminute, and norepinephrine administered intravenously wheneverthe mean arterial pressure remained lower than 60 mm Hg (theminimal dose that kept the pressure at or above 60 mm Hg).
After the patient's condition had been stabilized, respiratory,hemodynamic, and laboratory measurements were performed. Thesedata were used for a base-line comparison of the two groupsand for calculating the risk of death according to the severityof illness (Table 1). The physiologic data for Acute Physiologyand Chronic Health Evaluation (APACHE) II21 scores were collectedduring the 24-hour period starting at this time. The worst valuesduring this interval, including the control-period measurements,were recorded, except for blood gas and heart-rate values. Toavoid the overestimating effects of subsequent permissive hypercapniaon these variables (since respiratory acidosis and tachycardiausually increase the APACHE score), only the control-periodmeasurements of blood gas and heart rate were considered (adjustedAPACHE II score).
Subsequently, a bedside procedure was performed to calculatethe inspiratory and static pressure–volume curve withoutdisconnecting the ventilator, as described previously.15,22A well-defined PFLEX (corresponding to an upward shift in theslope of the curve and signaling an increment in lung compliance)could be determined for 49 patients, but the corresponding valuewas used to adjust PEEP only in the group assigned to protectivemechanical ventilation. Since this was the only curve calculatedduring the protocol, PEEP was then kept constant in this groupuntil the inspiratory oxygen fraction was less than 0.4.15 Afterdetermining the pressure–volume curve, we randomly assignedthe patients to one of the two groups. Randomization was performedwith sealed envelopes and a 1:1 assignment scheme.
General Ventilatory Support
Protective or conventional mechanical ventilation was rigorouslymaintained until the patient was extubated or died. Each patientwas connected to a closed system for aspirating tracheal secretions;the patient remained connected to the ventilator during aspiration,minimizing temporary drops in airway pressure. In both groups,the target partial pressure of arterial oxygen was 80 mm Hg,and the PEEP level was never set below 5 cm of water, even duringweaning from the ventilator. The weaning procedure was the samein the two groups: a gradual decrease in the level of pressuresupport.15 Patients received ventilation exclusively throughendotracheal tubes.
Conventional Approach
We sought to maintain an arterial carbon dioxide level of 35to 38 mm Hg, independent of airway pressures, and an inspiratoryoxygen fraction of less than 0.6 with adequate systemic oxygendelivery. To optimize this compromise, we used a stepwise algorithmfor PEEP increments.15,16 Other ventilatory settings were asfollows: tidal volume, 12 ml per kilogram (volume-cycled assistedor controlled ventilation); square-wave inspiratory flow rate,50 to 80 liters per minute (adjusted to avoid auto-PEEP, orabnormal gas trapping leading to an elevated end-respiratorypressure); inspiratory pause, 0.4 second; and backup respiratoryrate, 10 to 24 cycles per minute (depending on the value forarterial carbon dioxide). In addition to the administrationof sedative drugs to keep the patients comfortable, additionaldoses of sedatives were given to prevent patient-triggered respiratoryrates higher than 24 cycles per minute or arterial carbon dioxidevalues lower than 25 mm Hg.
Protective Approach
The protective approach was intended to prevent alveolar collapseand overdistention, regardless of arterial carbon dioxide levels,and to maintain an "open lung" independently of hemodynamicconditions. The tidal volume was maintained at a level lowerthan 6 ml per kilogram, with a respiratory rate of less than30 cycles per minute, even during pressure support. Permissivehypercapnia and continuous infusions of fentanyl and diazepamwere used to prevent discomfort and signs of increased respiratorydrive. Initial arterial carbon dioxide levels of up to 80 mmHg were allowed, and slow intravenous sodium bicarbonate infusions(<50 mmol per hour) were permitted if the arterial pH wasless than 7.2.
Driving pressures (PPLAT-PEEP, with PPLAT defined as the plateaupressure after the inspiratory pause) and peak airway pressureswere kept below 20 and 40 cm of water, respectively. Only pressure-limitedmodes of ventilation (pressure-controlled inverse-ratio ventilation[ratio of inspiration to expiration, >1] and pressure-supportventilation, both generating constant airway pressure duringinspiration) or combined modes (volume-ensured pressure-supportventilation, in which a constant inspiratory pressure is targetedat the same time that a minimal tidal volume is guaranteed23)were used, according to a stepwise algorithm.15
PEEP was preset at 2 cm of water above PFLEX. When auto-PEEP(defined as the difference between alveolar pressures at endexpiration and airway pressures) was present, the total PEEP(external PEEP plus auto-PEEP) was considered and adjusted toequal PFLEX plus 2 cm of water. Finally, if a sharp PFLEX couldnot be determined on the pressure–volume curve, an empiricaltotal-PEEP value of 16 cm of water was used.15 Recruiting maneuvers— aimed at reaerating alveolar units requiring very highopening pressures — were frequently used, especially afterinadvertent disconnections from the ventilator. Continuous positiveairway pressures of 35 to 40 cm of water were applied for 40seconds, followed by a careful return to previous PEEP levels.Finally, pressure-controlled inverse-ratio ventilation was usedwhenever the inspiratory oxygen fraction was higher than 0.5,in order to decrease minute-volume requirements.24
General Support
All patients were monitored with the Swan–Ganz catheter,and a stepwise algorithm for hemodynamic optimization15,16 wasused. Measurements of plasma lactate and mixed venous saturationwere used to correct imbalances between oxygen transport anddemand. The pulmonary-artery wedge pressure never exceeded 15mm Hg. Procedures for nutritional support, treatment of infections,and renal dialysis (when needed) were the same in both groups.15,16Corticosteroids were given only to patients with Pneumocystiscarinii pneumonia. No patients received immunotherapy. The protocolfor sedation was the same for both groups, with only two sedativesprescribed (fentanyl and diazepam) and only one neuromuscularparalyzing drug (pancuronium). Although larger doses (up to9 mg per day) were used in the protective-ventilation group,continuous infusions of fentanyl were used in both groups tokeep the patients comfortable. All patients received ranitidine(50 mg intravenously every eight hours) as prophylaxis againstbleeding.
Statistical Analysis
The primary end point was survival at 28 days. The effect ofthe protective approach was analyzed with a Cox proportional-hazardsmodel, with the base-line adjusted APACHE II score (adjustedrisk of death) included as a covariate.
After the first block of 28 patients had been enrolled, a beneficialeffect of the protective approach on pulmonary function becameevident,15 and we were concerned about the possibility of subjectingthe patients to an unnecessary continuation of the protocol.25Therefore, we performed an interim analysis after each new blockof five patients. We estimated that a maximal sample of 58 patientswas required, assuming a type I error of 5 percent, a statisticalpower of 85 percent, and a survival rate in the protective-ventilationgroup that would be 2.4 times that in the conventional-ventilationgroup, according to our initial results.15
To counterbalance the increased chance of prematurely stoppingthe study because of a type I error, we used the conservativecorrection for multiplicity proposed by Peto et al.26 and Gellerand Pocock,27 with a nominal significance level of <0.001for an interim analysis, if the study was stopped early, anda significance level of <0.04 for the final analysis, ifthe study was completed.27
The secondary end points were survival to hospital discharge,occurrence of clinically detectable barotrauma, and weaningrate adjusted for APACHE II score (Cox model). Bonferroni'sadjustment for multiple comparisons was performed for each secondaryend point. All other statistical tests are described below.All P values (two-tailed) were calculated with the BMDP softwarepackage (BMDP Statistical Software, version 7.0, Los Angeles).
Results
The study was stopped during the fifth interim analysis, after53 patients had been enrolled, because of a significant survivaldifference between the groups (Table 2 and Table 3 and Figure 1).After 28 days, 11 of 29 patients (38 percent) in the protective-ventilationgroup had died, as compared with 17 of 24 (71 percent) in theconventional-ventilation group (P<0.001). The results weresimilar when the groups were stratified according to the initialseverity of illness or the center where the patient was treated.
Figure 1. Actuarial 28-Day Survival among 53 Patients with the Acute Respiratory Distress Syndrome Assigned to Protective or Conventional Mechanical Ventilation.
The data are based on an intention-to-treat analysis. The P value indicates the effect of ventilatory treatment as estimated by the Cox regression model, with the risk of death associated with the adjusted base-line score on APACHE II included as a covariate.
The difference in weaning rates mirrored the results for survival,with 19 of 29 patients (66 percent) in the protective-ventilationgroup successfully weaned from the ventilator, as compared with7 of 24 (29 percent) in the conventional-ventilation group (P= 0.005 after adjustment for multiple comparisons). The rateof clinical barotrauma was also significantly lower in the protective-ventilationgroup than in the conventional-ventilation group (7 percentvs. 42 percent, P = 0.02 after adjustment for multiple comparisons).The difference in survival to hospital discharge was not significant;13 of 29 patients in the protective-ventilation group (45 percent)died in the hospital, as compared with 17 of 24 patients inthe conventional-ventilation group (71 percent, P = 0.37 afteradjustment for multiple comparisons).
Within the first 28 days, the most frequent causes of deathwere refractory septic shock and progressive respiratory failure(Table 2).15 Fourteen episodes of accidental extubation (usuallyduring repositioning of the patient) occurred in nine patientsin the protective-ventilation group, as compared with 10 episodesin seven patients in the conventional-ventilation group. Intwo of the patients in the protective-ventilation group andone in the conventional-ventilation group, irreversible cardiacevents followed these episodes. Although successfully extubated(at >48 hours), four patients in the protective-ventilationgroup died before hospital discharge: one from massive hemothoraxwith arterial rupture during attempts at central venous cannulation(on day 7), one from diffuse gastrointestinal bleeding (on day23), one from intracerebral nocardiosis with brain edema (onday 11), and one from a new episode of nosocomial pneumoniafollowed by refractory septic shock (on day 68). Except forthe episode of arterial rupture, no iatrogenic event relatedto central lines occurred after study entry.
The values for the respiratory variables measured during thefirst week of the study are shown in Table 4. The objectivesof ventilatory support were achieved in 48 of the 53 patients.Although the mean respiratory values suggest good adherenceto the protocol, there were minor protocol violations in thecare of four patients in the protective-ventilation group andone patient in the conventional-ventilation group. In the patientin the conventional-ventilation group, a tidal volume of 7 mlper kilogram was inadvertently used for 12 hours. Among theviolations in the protective-ventilation group, there was aninadvertent use of a tidal volume higher than 7 ml per kilogramduring a period of eight hours, a PEEP prematurely reduced indisregard of the protocol, use of antibiotics in disregard ofthe protocol, and a previous pneumothorax detected during acareful review of radiographs. The exclusion of these five patientsfrom the analysis of mortality had little effect on the mortalityrate associated with the protective-ventilation approach (relativerisk of death, 0.14 [95 percent confidence interval, 0.05 to0.38], as compared with 0.19 [95 percent confidence interval,0.08 to 0.47]). The protective-ventilation approach had significantbenefits with regard to oxygenation and lung compliance.
Table 4. Respiratory Values during the First Week of Mechanical Ventilation.
Table 3 shows the results of univariate and multivariate analysesof mortality at 28 days according to base-line factors (datacollected during the control period before randomization). TheAPACHE II scores and the ventilatory treatment were the onlysignificant factors. These were the two covariates that hadbeen included a priori in the final multivariate Cox regressionmodel.
Discussion
We found that in a group of patients with severe acute respiratorydistress syndrome, the protective approach to mechanical ventilationimproved the survival rate at 28 days and the weaning rate butnot the rate of survival to hospital discharge. The incidenceof barotrauma was significantly lower in the protective-ventilationgroup than in the conventional-ventilation group, despite theuse of higher PEEP levels and higher mean airway pressures.
The complexity of the procedures in this study precluded theuse of a protocol in which the investigators were unaware ofthe treatment assignments. Nevertheless, we believe that thestringent algorithms used for infectious problems, hemodynamicvalues, nutrition, sedation, dialysis, and general care15 weresufficient to minimize additional bias due to differences inthe management of nonrespiratory problems. We demonstrated ina previous analysis that we were able to accomplish the plannedhemodynamic goals in most patients in both groups.16 Finally,it is difficult to ascribe the better outcome in the protective-ventilationgroup to uncontrolled or unrecognized factors, since our staffwas much more used to the conventional approach. In fact, agreater number of fatal iatrogenic accidents occurred in theprotective-ventilation group than in the conventional-ventilationgroup. Considering the small size of the study, the conservativenature of Bonferroni's statistical adjustment,27 and the severityof base-line disease in the patients (which was responsiblefor many of the late deaths), the failure to detect a significantdifference in survival to hospital discharge was not surprising.
Despite the use of an appropriate rule for early terminationof the study during all interim analyses,26,27 the estimatesof relative risk shown in Table 3 may be imprecise. The correctionsproposed for multiple sequential analysis can properly controlthe overall type I error, but they cannot prevent associateddistortions of the magnitude of the treatment effect causedby early termination or the small sample.28
Since the effect of the protective-ventilation strategy on survivalwas observed in the context of many concomitant maneuvers (permissivehypercapnia, lower peak and driving pressures, higher PEEP,a tidal volume of less than 6 ml per kilogram, and so forth),we performed a pooled "retrospective" analysis to determinethe key combination of ventilatory variables responsible forthe ventilatory treatment effect on mortality at 28 days (datanot shown). When the treatment assignment was removed from theCox mortality model, there were three significant prognosticfactors: the APACHE II score, the mean PEEP used during thefirst 36 hours (with a protective effect indicated by a coefficientof -0.15), and the driving pressures (PPLAT-PEEP) during thefirst 36 hours (with a deleterious effect of high driving pressuresindicated by a coefficient of 0.06). All other respiratory variableswere of secondary importance. Higher PEEP values (preferentiallyabove the PFLEX value) and lower driving pressures were independentlyassociated with better survival. High initial PEEP values appearedto be beneficial, even when the PPLAT value increased, as longas the driving pressure did not change disproportionately.
The strong protective effect associated with a high PEEP valueis consistent with recent experimental data,7,29,30,31,32,33and the benefit seems to be more pronounced than the deleteriouseffect of high distending pressures.7,29,30 Had we not usedhigh PEEP levels (>PFLEX), the results might have been verydifferent, with the isolated reduction in PPLAT potentiallycausing reabsorption atelectasis, loss of alveolar surface,and hypoxemia in some patients.
Recent evidence suggests that the minimization of ventilator-inducedlung injury may have important systemic benefits, decreasingthe release of proinflammatory mediators,34,35,36 the disseminationof infections,37,38,39 and possible complications related toair embolism.40,41 In addition to preventing progressive respiratoryfailure, the protective-ventilation approach may be associatedwith these mechanisms.
Despite the use of higher PEEP values (up to 24 cm of water)and higher mean airway pressures, there was a lower incidenceof barotrauma in the protective-ventilation group. The protective-ventilationapproach may thus not only improve pulmonary function and oxygenationbut also reduce clinically apparent alveolar damage. Anotherstudy suggested a protective effect of PEEP against clinicalbarotrauma.42 The paucity of data in favor of this concept maybe explained by the correlation normally found between PEEPand peak pressures.43,44 In our study, however, the use of highPEEP levels did not necessarily result in high peak or plateaupressures.
Supported by the Laboratório de InvestigaçãoMédica, Hospital das Clínicas, University of SãoPaulo, and Intermed Equipamento Médico Hospitalar.
We are indebted to Drs. Eduardo C. Meyer, Mauro R. Tucci, PedroCaruso, Ivany A.L. Schettino, Cristiane Hoelz, Elnara Negri,Chin An Lin, Eloisa A. Silva, Vasco Moskovitz, Laerte Pastore,Fabio Gomes, Sergio Demarzo, Cristiane Morais, Eduardo de OliveiraFernandes, Marcia Xavier Barreto, Marco Ferreira, Mauro Kaufmann,Luis Alexandre Borges, Jorge Höher, Jairo Othero, LuisA. Azambuja, Gilberto Friedman, Michelle Grunauer, and all theresidents working in our units during the study period for theirdedication and collaboration in providing care to the patients;to Dr. Rosangela Santoro de Souza Amato for her assistance inthe preparation of the manuscript; to Intermed Equipamento MédicoHospitalar and Siemens–Elema for technical support; andespecially to Dr. John J. Marini for his stimulating discussionsand helpful comments.
Source Information
From the Respiratory Intensive Care Unit, Pulmonary Division, Hospital das Clínicas, University of São Paulo (M.B.P.A., C.S.V.B., D.M.M., R.B.M., G.P.P.S., G.L.-F., R.A.K., D.D., T.Y.T., C.R.R.C.); and the General Intensive Care Unit, Santa Casa de Misericórdia, Porto Alegre (C.M., R.O.) — both in Brazil. Presented in part at the International Conference of the American Lung Association and the American Thoracic Society, New Orleans, May 10–15, 1996.
Address reprint requests to Dr. Amato at 135 Rua Dr. Joel Lagos, CEP 05344-000 São Paulo, Brazil.
References
Snyder JV, Froese A. Respirator lung. In: Snyder JV, Pinsky MR, eds. Oxygen transport in the critically ill. Chicago: Year Book Medical Publishers, 1987:358-73.
Marini JJ. Ventilation of the acute respiratory distress syndrome: looking for Mr. Goodmode. Anesthesiology 1994;80:972-975. [Medline]
Fu Z, Costello ML, Tsukimoto K, et al. High lung volume increases stress failure in pulmonary capillaries. J Appl Physiol 1992;73:123-133. [Free Full Text]
Carlton DP, Cummings JJ, Scheerer RG, Poulain FR, Bland RD. Lung overexpansion increases pulmonary microvascular protein permeability in young lambs. J Appl Physiol 1990;69:577-583. [Free Full Text]
Parker JC, Hernandez LA, Longenecker GL, Peevy K, Johnson W. Lung edema caused by high peak inspiratory pressures in dogs: role of increased microvascular filtration pressure and permeability. Am Rev Respir Dis 1990;142:321-328. [Medline]
Tsuno K, Prato P, Kolobow T. Acute lung injury from mechanical ventilation at moderately high airway pressures. J Appl Physiol 1990;69:956-961. [Free Full Text]
Dreyfuss D, Saumon G. Role of tidal volume, FRC, and end-inspiratory volume in the development of pulmonary edema following mechanical ventilation. Am Rev Respir Dis 1993;148:1194-1203. [Medline]
Hickling KG, Henderson SJ, Jackson R. Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med 1990;16:372-377. [CrossRef][Medline]
Hickling KG, Walsh J, Henderson S, Jackson R. Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: a prospective study. Crit Care Med 1994;22:1568-1578. [Medline]
Gattinoni L, Pesenti A, Mascheroni D, et al. Low-frequency positive-pressure ventilation with extracorporeal CO2 removal in severe acute respiratory failure. JAMA 1986;256:881-886. [Free Full Text]
Lee PC, Helsmoortel CM, Cohn SM, Fink MP. Are low tidal volumes safe? Chest 1990;97:430-434. [Free Full Text]
Mathieu-Costello O, Willford DC, Fu Z, Garden RM, West JB. Pulmonary capillaries are more resistant to stress failure in dogs than in rabbits. J Appl Physiol 1995;79:908-917. [Free Full Text]
Albert RK. Least PEEP: primum non nocere. Chest 1985;87:2-4. [Free Full Text]
Petty TL. The use, abuse, and mystique of positive end-expiratory pressure. Am Rev Respir Dis 1988;138:475-478. [Medline]
Amato MBP, Barbas CSV, Medeiros DM, et al. Beneficial effects of the "open lung approach" with low distending pressures in acute respiratory distress syndrome: a prospective randomized study on mechanical ventilation. Am J Respir Crit Care Med 1995;152:1835-1846. [Abstract]
Carvalho CRR, Barbas CSV, Medeiros DM, et al. Temporal hemodynamic effects of permissive hypercapnia associated with ideal PEEP in ARDS. Am J Respir Crit Care Med 1997;156:1458-1466. [Free Full Text]
Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 1988;138:720-723. [Erratum, Rev Respir Dis 1989;139:1065.] [Medline]
Teboul JL, Besbes M, Andrivet P, et al. A bedside index assessing the reliability of pulmonary artery occlusion pressure measurements during mechanical ventilation with positive end-expiratory pressure. J Crit Care 1992;7:22-29. [CrossRef]
Yeung HC, Lu MW, Martinez EG, Puri VK. Critical Care Scoring System -- new concept based on hemodynamic data. Crit Care Med 1990;18:1347-1352. [Medline]
Smith PEM, Gordon IJ. An index to predict outcome in adult respiratory distress syndrome. Intensive Care Med 1986;12:86-89. [Medline]
Knaus WA, Draper EA, Wagner DP, Zimmerman JE. Apache II: a severity of disease classification system. Crit Care Med 1985;13:818-829. [Medline]
Amato MBP, Barbas CSV, Meyer EC, Grunauer MA, Magaldi RB, Carvalho CRR. Setting the "best PEEP" in ARDS: limitations of choosing the PEEP according to the "best compliance." Am J Respir Crit Care Med 1995;151:Suppl:A550-A550.abstract
Amato MBP, Barbas CSV, Bonassa J, Saldiva PHN, Zin WA, Carvalho CRR. Volume-assured pressure support ventilation (VAPSV): a new approach for reducing muscle workload during acute respiratory failure. Chest 1992;102:1225-1234. [Free Full Text]
Gattinoni L, Mascheroni D, Borelli M, Basilico E, Pesenti A. Ventilation in severe ARDS: inverted ratio ventilation and CO2 removal. In: Lemaire F, ed. Mechanical ventilation. Berlin, Germany: Springer-Verlag, 1991:129-45.
Pocock SJ. When to stop a clinical trial. BMJ 1992;305:235-240.
Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. Br J Cancer 1976;34:585-612. [Medline]
Geller NL, Pocock SJ. Interim analysis in randomized clinical trials: ramifications and guidelines for practitioners. Biometrics 1987;43:213-223. [CrossRef][Medline]
Pocock SJ, Hughes MD. Estimation issues in clinical trials and overviews. Stat Med 1990;9:657-671. [Medline]
Muscedere JG, Mullen JBM, Gan K, Slutsky AS. Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med 1994;149:1327-1334. [Abstract]
Bshouty Z, Ali J, Younes M. Effect of tidal volume and PEEP on rate of edema formation in in situ perfused canine lobes. J Appl Physiol 1988;64:1900-1907. [Free Full Text]
Sandhar BK, Niblett DJ, Argiras EP, Dunnill MS, Sykes MK. Effects of positive end-expiratory pressure on hyaline membrane formation in a rabbit model of the neonatal respiratory distress syndrome. Intensive Care Med 1988;14:538-546. [CrossRef][Medline]
Argiras EP, Blakeley CR, Dunnill MS, Otremski S, Sykes MK. High PEEP decreases hyaline membrane formation in surfactant deficient lungs. Br J Anaesth 1987;59:1278-1285. [Free Full Text]
Wyszogrodski I, Kyei-Aboagye K, Taeusch HW Jr, Avery ME. Surfactant inactivation by hyperventilation: conservation by end-expiratory pressure. J Appl Physiol 1975;38:461-466. [Free Full Text]
Edmonds HL Jr, Spohr RW, Finnegan RF, et al. Indomethacin pretreatment in continuous positive-pressure ventilation. Crit Care Med 1981;9:524-529. [Medline]
Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS. Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest 1997;99:944-952. [Medline]
Sugiura M, McCulloch PR, Wren S, Dawson RH, Froese AB. Ventilator pattern influences neutrophil influx and activation in atelectasis-prone rabbit lung. J Appl Physiol 1994;77:1355-1365. [Free Full Text]
Tilson MD, Bunke MC, Smith GJ, et al. Quantitative bacteriology and pathology of the lung in experimental Pseudomonas pneumonia treated with positive end-expiratory pressure (PEEP). Surgery 1977;82:133-140. [Medline]
Johanson WG Jr, Higuchi JH, Woods DE, Gomez P, Coalson JJ. Dissemination of Pseudomonas aeruginosa during lung infection in hamsters: role of oxygen-induced lung injury. Am Rev Respir Dis 1985;132:358-361. [Medline]
Nahum A, Hoyt J, McKibben A, et al. Effect of mechanical ventilation strategy on E. coli pneumonia in dogs. Am J Respir Crit Care Med 1996;153:Suppl:A531-A531.abstract
Marini JJ, Culver BH. Systemic gas embolism complicating mechanical ventilation in the adult respiratory distress syndrome. Ann Intern Med 1989;110:699-703.
Gregory GA, Tooley WH. Gas embolism in hyaline-membrane disease. N Engl J Med 1970;282:1141-1142.
Mathru M, Rao TLK, Venus B. Ventilator-induced barotrauma in controlled mechanical ventilation versus intermittent mandatory ventilation. Crit Care Med 1983;11:359-361. [Medline]
Petersen GW, Baier H. Incidence of pulmonary barotrauma in a medical ICU. Crit Care Med 1983;11:67-69. [Medline]
Zwillich CW, Pierson DJ, Creagh CE, Sutton FD, Schatz E, Petty TL. Complications of assisted ventilation: a prospective study of 354 consecutive episodes. Am J Med 1974;57:161-170. [CrossRef][Medline]
Protective Ventilation for the Acute Respiratory Distress Syndrome
Chiche J.-D., Brunet F., Lamy M., Kacmarek R., Parsons P. E., Matthay M., Manning H. L., Shapira M. Y., Sviri S., Linton D. M., Weg J. G., Anzueto A., Amato M. B.P., Barbas C. S.V., Carvalho C. R.R., Stewart T. E., Meade M. O., Slutsky A. S.
Extract |
Full Text
N Engl J Med 1998;
339:196-199, Jul 16, 1998.
Correspondence
This article has been cited by other articles:
Weingarten, T. N., Whalen, F. X., Warner, D. O., Gajic, O., Schears, G. J., Snyder, M. R., Schroeder, D. R., Sprung, J.
(2009). Comparison of two ventilatory strategies in elderly patients undergoing major abdominal surgery. Br J Anaesth
0: aep319v1-aep319
[Abstract][Full Text]
Kesecioglu, J., Beale, R., Stewart, T. E., Findlay, G. P., Rouby, J.-J., Holzapfel, L., Bruins, P., Steenken, E. J., Jeppesen, O. K., Lachmann, B.
(2009). Exogenous Natural Surfactant for Treatment of Acute Lung Injury and the Acute Respiratory Distress Syndrome. Am. J. Respir. Crit. Care Med.
180: 989-994
[Abstract][Full Text]
Amaral, A. C. K. B.
(2009). Polymyxin B Hemoperfusion and Mortality in Abdominal Septic Shock. JAMA
302: 1968-1969
[Full Text]
Antonelli, M., Giunta, F., Ronco, C.
(2009). Polymyxin B Hemoperfusion and Mortality in Abdominal Septic Shock--Reply. JAMA
302: 1969-1970
[Full Text]
Kwang Joo Park, , Yoon Jung Oh, , Hyuk Jae Chang, , Seung Soo Sheen, , Choi, J., Keu Sung Lee, , Joo Hun Park, , Sung Chul Hwang,
(2009). Acute Hemodynamic Effects of Recruitment Maneuvers in Patients With Acute Respiratory Distress Syndrome. J Intensive Care Med
24: 376-382
[Abstract]
Yalcin, H. C., Hallow, K. M., Wang, J., Wei, M. T., Ou-Yang, H. D., Ghadiali, S. N.
(2009). Influence of cytoskeletal structure and mechanics on epithelial cell injury during cyclic airway reopening. Am. J. Physiol. Lung Cell. Mol. Physiol.
297: L881-L891
[Abstract][Full Text]
Masood, A., Yi, M., Lau, M., Belcastro, R., Shek, S., Pan, J., Kantores, C., McNamara, P. J., Kavanagh, B. P., Belik, J., Jankov, R. P., Tanswell, A. K.
(2009). Therapeutic effects of hypercapnia on chronic lung injury and vascular remodeling in neonatal rats. Am. J. Physiol. Lung Cell. Mol. Physiol.
297: L920-L930
[Abstract][Full Text]
Putensen, C., Theuerkauf, N., Zinserling, J., Wrigge, H., Pelosi, P.
(2009). Meta-analysis: Ventilation Strategies and Outcomes of the Acute Respiratory Distress Syndrome and Acute Lung Injury. ANN INTERN MED
151: 566-576
[Abstract][Full Text]
Bickenbach, J., Zoremba, N., Fries, M., Dembinski, R., Doering, R., Ogawa, E., Rossaint, R., Kuhlen, R.
(2009). Low Tidal Volume Ventilation in a Porcine Model of Acute Lung Injury Improves Cerebral Tissue Oxygenation. Anesth. Analg.
109: 847-855
[Abstract][Full Text]
Brenner, B., Corbridge, T., Kazzi, A.
(2009). Intubation and Mechanical Ventilation of the Asthmatic Patient in Respiratory Failure. Proc Am Thorac Soc
6: 371-379
[Full Text]
Azzam, H. C, Khalsa, S. S, Urbani, R., Shah, C. V, Christie, J. D, Lanken, P. N, Fuchs, B. D
(2009). Validation Study of an Automated Electronic Acute Lung Injury Screening Tool. J Am Med Inform Assoc
16: 503-508
[Abstract][Full Text]
Azzam, H. C., Khalsa, S. S., Urbani, R., Shah, C. V., Christie, J. D., Lanken, P. N., Fuchs, B. D.
(2009). Validation Study of an Automated Electronic Acute Lung Injury Screening Tool. J. Am. Med. Inform. Assoc.
16: 503-508
[Abstract][Full Text]
Stawicki, S.P., Goyal, M., Sarani, B.
(2009). Analytic Reviews: High-Frequency Oscillatory Ventilation (HFOV) and Airway Pressure Release Ventilation (APRV): A Practical Guide. J Intensive Care Med
24: 215-229
[Abstract]
Zimmerman, J. J., Akhtar, S. R., Caldwell, E., Rubenfeld, G. D.
(2009). Incidence and Outcomes of Pediatric Acute Lung Injury. Pediatrics
124: 87-95
[Abstract][Full Text]
Nehra, D., Goldstein, A. M., Doody, D. P., Ryan, D. P., Chang, Y., Masiakos, P. T.
(2009). Extracorporeal Membrane Oxygenation for Nonneonatal Acute Respiratory Failure: The Massachusetts General Hospital Experience From 1990 to 2008. Arch Surg
144: 427-432
[Abstract][Full Text]
Spieth, P. M., Carvalho, A. R., Pelosi, P., Hoehn, C., Meissner, C., Kasper, M., Hubler, M., von Neindorff, M., Dassow, C., Barrenschee, M., Uhlig, S., Koch, T., de Abreu, M. G.
(2009). Variable Tidal Volumes Improve Lung Protective Ventilation Strategies in Experimental Lung Injury. Am. J. Respir. Crit. Care Med.
179: 684-693
[Abstract][Full Text]
Albert, S. P., DiRocco, J., Allen, G. B., Bates, J. H. T., Lafollette, R., Kubiak, B. D., Fischer, J., Maroney, S., Nieman, G. F.
(2009). The role of time and pressure on alveolar recruitment. J. Appl. Physiol.
106: 757-765
[Abstract][Full Text]
Ghadiali, S. N.
(2009). Making "time" for alveolar recruitment. J. Appl. Physiol.
106: 751-752
[Full Text]
Varpula, T., Valta, P., Markkola, A., Pohjanen, K., Halavaara, J., Hynynen, M., Pettila, V.
(2009). The Effects of Ventilatory Mode on Lung Aeration Assessed With Computer Tomography: A Randomized Controlled Study. J Intensive Care Med
24: 122-130
[Abstract]
Gusmao, D., Tanner, A. C., Teles, J. M., Valentini, R., Rodriguez, P., Bonelli, I., Walkey, A. J., Vieillard-Baron, A., Jardin, F., Talmor, D., Malhotra, A., Loring, S. H.
(2009). Esophageal Pressure in Acute Lung Injury. NEJM
360: 831-833
[Full Text]
Kopterides, P., Kapetanakis, T., Siempos, I. I., Magkou, C., Pelekanou, A., Tsaganos, T., Giamarellos-Bourboulis, E., Roussos, C., Armaganidis, A.
(2009). Short-Term Administration of a High Oxygen Concentration Is Not Injurious in an Ex-Vivo Rabbit Model of Ventilator-Induced Lung Injury. Anesth. Analg.
108: 556-564
[Abstract][Full Text]
Schmidt, G. A.
(2009). Mechanical Ventilation. ACCP Crit Care Med Brd Rev
20: 157-170
[Full Text]
Kress, J. P.
(2009). Acute Respiratory Distress Syndrome. ACCP Crit Care Med Brd Rev
20: 279-288
[Full Text]
Hoeper, M. M., Welte, T.
(2008). Extracorporeal lung assist: more than kicking a dead horse?. Eur Respir J
32: 1431-1432
[Full Text]
Diaz, L. A., Mortensen, E. M., Anzueto, A., Restrepo, M. I.
(2008). Review: Novel targets in the management of pneumonia. Ther Adv Respir Dis
2: 387-400
[Abstract]
Fan, E., Wilcox, M. E., Brower, R. G., Stewart, T. E., Mehta, S., Lapinsky, S. E., Meade, M. O., Ferguson, N. D.
(2008). Recruitment Maneuvers for Acute Lung Injury: A Systematic Review. Am. J. Respir. Crit. Care Med.
178: 1156-1163
[Abstract][Full Text]
Bernard, G. R.
(2008). PEEP Guided by Esophageal Pressure -- Any Added Value?. NEJM
359: 2166-2168
[Full Text]
Talmor, D., Sarge, T., Malhotra, A., O'Donnell, C. R., Ritz, R., Lisbon, A., Novack, V., Loring, S. H.
(2008). Mechanical Ventilation Guided by Esophageal Pressure in Acute Lung Injury. NEJM
359: 2095-2104
[Abstract][Full Text]
Yiming, M. T., Lederer, D. J., Sun, L., Huertas, A., Issekutz, A. C., Bhattacharya, S.
(2008). Platelets Enhance Endothelial Adhesiveness in High Tidal Volume Ventilation. Am. J. Respir. Cell Mol. Bio.
39: 569-575
[Abstract][Full Text]
Davis, J L, Morris, A, Kallet, R H, Powell, K, Chi, A S, Bensley, M, Luce, J M, Huang, L
(2008). Low tidal volume ventilation is associated with reduced mortality in HIV-infected patients with acute lung injury. Thorax
63: 988-993
[Abstract][Full Text]
Malhotra, A, Hillman, D
(2008). Obesity and the lung: 3 {middle dot} Obesity, respiration and intensive care. Thorax
63: 925-931
[Abstract][Full Text]
Dongelmans, D. A., Veelo, D. P., Bindels, A., Binnekade, J. M., Koppenol, K., Koopmans, M., Korevaar, J. C., Kuiper, M. A., Schultz, M. J.
(2008). Determinants of Tidal Volumes with Adaptive Support Ventilation: A Multicenter Observational Study. Anesth. Analg.
107: 932-937
[Abstract][Full Text]
Haitsma, J. J., Pelosi, P.
(2008). Ventilation Strategies for Acute Lung Injury and Acute Respiratory Distress Syndrome. JAMA
300: 39-39
[Full Text]
Heunks, L. M. A., van der Hoeven, J. G.
(2008). Ventilation Strategies for Acute Lung Injury and Acute Respiratory Distress Syndrome. JAMA
300: 40-41
[Full Text]
Lytle, F. T., Brown, D. R.
(2008). Appropriate Ventilatory Settings for Thoracic Surgery: Intraoperative and Postoperative. SEMIN CARDIOTHORAC VASC ANESTH
12: 97-108
[Abstract]
Agarwal, R., Srinivas, R., Nath, A., Jindal, S. K.
(2008). Is the Mortality Higher in the Pulmonary vs the Extrapulmonary ARDS?: A Metaanalysis. Chest
133: 1463-1473
[Abstract][Full Text]
Checkley, W., Brower, R., Korpak, A., Thompson, B. T., for the Acute Respiratory Distress Syndrome Networ,
(2008). Effects of a Clinical Trial on Mechanical Ventilation Practices in Patients with Acute Lung Injury. Am. J. Respir. Crit. Care Med.
177: 1215-1222
[Abstract][Full Text]
Otto, C. M., Markstaller, K., Kajikawa, O., Karmrodt, J., Syring, R. S., Pfeiffer, B., Good, V. P., Frevert, C. W., Baumgardner, J. E.
(2008). Spatial and temporal heterogeneity of ventilator-associated lung injury after surfactant depletion. J. Appl. Physiol.
104: 1485-1494
[Abstract][Full Text]
Thammanomai, A., Hueser, L. E., Majumdar, A., Bartolak-Suki, E., Suki, B.
(2008). Design of a new variable-ventilation method optimized for lung recruitment in mice. J. Appl. Physiol.
104: 1329-1340
[Abstract][Full Text]
Fernandez-Perez, E. R., Yilmaz, M., Jenad, H., Daniels, C. E., Ryu, J. H., Hubmayr, R. D., Gajic, O.
(2008). Ventilator Settings and Outcome of Respiratory Failure in Chronic Interstitial Lung Disease. Chest
133: 1113-1119
[Abstract][Full Text]
Jia, X., Malhotra, A., Saeed, M., Mark, R. G., Talmor, D.
(2008). Risk Factors for ARDS in Patients Receiving Mechanical Ventilation for > 48 h. Chest
133: 853-861
[Abstract][Full Text]
Liu, K. D., Matthay, M. A.
(2008). Advances in Critical Care for the Nephrologist: Acute Lung Injury/ARDS. CJASN
3: 578-586
[Abstract][Full Text]
Meade, M. O., Cook, D. J., Guyatt, G. H., Slutsky, A. S., Arabi, Y. M., Cooper, D. J., Davies, A. R., Hand, L. E., Zhou, Q., Thabane, L., Austin, P., Lapinsky, S., Baxter, A., Russell, J., Skrobik, Y., Ronco, J. J., Stewart, T. E., for the Lung Open Ventilation Study Investigators,
(2008). Ventilation Strategy Using Low Tidal Volumes, Recruitment Maneuvers, and High Positive End-Expiratory Pressure for Acute Lung Injury and Acute Respiratory Distress Syndrome: A Randomized Controlled Trial. JAMA
299: 637-645
[Abstract][Full Text]
Mercat, A., Richard, J.-C. M., Vielle, B., Jaber, S., Osman, D., Diehl, J.-L., Lefrant, J.-Y., Prat, G., Richecoeur, J., Nieszkowska, A., Gervais, C., Baudot, J., Bouadma, L., Brochard, L., for the Expiratory Pressure (Express) Study Group,
(2008). Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome: A Randomized Controlled Trial. JAMA
299: 646-655
[Abstract][Full Text]
Determann, R. M., Wolthuis, E. K., Choi, G., Bresser, P., Bernard, A., Lutter, R., Schultz, M. J.
(2008). Lung epithelial injury markers are not influenced by use of lower tidal volumes during elective surgery in patients without preexisting lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol.
294: L344-L350
[Abstract][Full Text]
Bream-Rouwenhorst, H. R., Beltz, E. A., Ross, M. B., Moores, K. G.
(2008). Recent developments in the management of acute respiratory distress syndrome in adults. Am J Health Syst Pharm
65: 29-36
[Abstract][Full Text]
Mukhtar, A. M., Obayah, G. M., Elmasry, A., Dessouky, N. M.
(2008). The Therapeutic Potential of Intraoperative Hypercapnia During Video-Assisted Thoracoscopy in Pediatric Patients. Anesth. Analg.
106: 84-88
[Abstract][Full Text]
Mikhail, A., van der Putten, K., Braam, B., Gaillard, C. A., Eisen, L. A., Cooke, C. R., Rubenfeld, G. D., Corwin, H. L.
(2007). Epoetin Alfa in Critically Ill Patients. NEJM
357: 2515-2517
[Full Text]
Borri, A., Leo, F., Veronesi, G., Solli, P., Galetta, D., Gasparri, R., Petrella, F., Scanagatta, P., Radice, D., Spaggiari, L.
(2007). Extended pneumonectomy for non-small cell lung cancer: morbidity, mortality, and long-term results.. J. Thorac. Cardiovasc. Surg.
134: 1266-1272
[Abstract][Full Text]
Yalcin, H. C., Perry, S. F., Ghadiali, S. N.
(2007). Influence of airway diameter and cell confluence on epithelial cell injury in an in vitro model of airway reopening. J. Appl. Physiol.
103: 1796-1807
[Abstract][Full Text]
Thammanomai, A., Majumdar, A., Bartolak-Suki, E., Suki, B.
(2007). Effects of reduced tidal volume ventilation on pulmonary function in mice before and after acute lung injury. J. Appl. Physiol.
103: 1551-1559
[Abstract][Full Text]
Thompson, B. T., Schoenfeld, D.
(2007). Usual Care as the Control Group in Clinical Trials of Nonpharmacologic Interventions. Proc Am Thorac Soc
4: 577-582
[Abstract][Full Text]
Henzler, D., Hochhausen, N., Dembinski, R., Orfao, S., Rossaint, R., Kuhlen, R.
(2007). Parameters Derived from the Pulmonary Pressure Volume Curve, but Not the Pressure Time Curve, Indicate Recruitment in Experimental Lung Injury. Anesth. Analg.
105: 1072-1078
[Abstract][Full Text]
Malhotra, A.
(2007). Low-Tidal-Volume Ventilation in the Acute Respiratory Distress Syndrome. NEJM
357: 1113-1120
[Full Text]
Desai, L. P., Sinclair, S. E., Chapman, K. E., Hassid, A., Waters, C. M.
(2007). High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesion. Am. J. Physiol. Lung Cell. Mol. Physiol.
293: L769-L778
[Abstract][Full Text]
Girard, T. D., Bernard, G. R.
(2007). Mechanical Ventilation in ARDS: A State-of-the-Art Review. Chest
131: 921-929
[Abstract][Full Text]
Ota, S., Nakamura, K., Yazawa, T., Kawaguchi, Y., Baba, Y., Kitaoka, R., Morimura, N., Goto, T., Yamada, Y., Kurahashi, K.
(2007). High tidal volume ventilation induces lung injury after hepatic ischemia-reperfusion. Am. J. Physiol. Lung Cell. Mol. Physiol.
292: L625-L631
[Abstract][Full Text]
Ozcan, P. E., Cakar, N., Tugrul, S., Akinci, O., Cagatay, A., Yilmazbayhan, D., Esen, F., Telci, L., Akpir, K.
(2007). The Effects of Airway Pressure and Inspiratory Time on Bacterial Translocation. Anesth. Analg.
104: 391-396
[Abstract][Full Text]
Allen, G. B., Suratt, B. T., Rinaldi, L., Petty, J. M., Bates, J. H. T.
(2006). Choosing the frequency of deep inflation in mice: balancing recruitment against ventilator-induced lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol.
291: L710-L717
[Abstract][Full Text]
Riedel, T., Fraser, J. F., Dunster, K., Fitzgibbon, J., Schibler, A.
(2006). Effect of smoke inhalation on viscoelastic properties and ventilation distribution in sheep. J. Appl. Physiol.
101: 763-770
[Abstract][Full Text]
Luecke, T., Meinhardt, J. P., Herrmann, P., Weiss, A., Quintel, M., Pelosi, P.
(2006). Oleic Acid vs Saline Solution Lung Lavage-Induced Acute Lung Injury: Effects on Lung Morphology, Pressure-Volume Relationships, and Response to Positive End-Expiratory Pressure.. Chest
130: 392-401
[Abstract][Full Text]
Borges, J. B., Okamoto, V. N., Matos, G. F. J., Caramez, M. P. R., Arantes, P. R., Barros, F., Souza, C. E., Victorino, J. A., Kacmarek, R. M., Barbas, C. S. V., Carvalho, C. R. R., Amato, M. B. P.
(2006). Reversibility of Lung Collapse and Hypoxemia in Early Acute Respiratory Distress Syndrome. Am. J. Respir. Crit. Care Med.
174: 268-278
[Abstract][Full Text]
Galiatsou, E., Kostanti, E., Svarna, E., Kitsakos, A., Koulouras, V., Efremidis, S. C., Nakos, G.
(2006). Prone Position Augments Recruitment and Prevents Alveolar Overinflation in Acute Lung Injury. Am. J. Respir. Crit. Care Med.
174: 187-197
[Abstract][Full Text]
Cho, M. H., Malhotra, A., Donahue, D. M., Wain, J. C., Harris, R. S., Karmpaliotis, D., Patel, S. R.
(2006). Mechanical ventilation and air leaks after lung biopsy for acute respiratory distress syndrome.. Ann. Thorac. Surg.
82: 261-266
[Abstract][Full Text]
Macnaughton, P. D.
(2006). New ventilators for the ICU--usefulness of lung performance reporting. Br J Anaesth
97: 57-63
[Abstract][Full Text]
Hall, N. G., Liu, Y., Hickman-Davis, J. M., Davis, G. C., Myles, C., Andrews, E. J., Matalon, S., Lang, J. D. Jr.
(2006). Bactericidal Function of Alveolar Macrophages in Mechanically Ventilated Rabbits. Am. J. Respir. Cell Mol. Bio.
34: 719-726
[Abstract][Full Text]
Pfeiffer, B., Syring, R. S., Markstaller, K., Otto, C. M., Baumgardner, J. E.
(2006). The implications of arterial po2 oscillations for conventional arterial blood gas analysis.. Anesth. Analg.
102: 1758-1764
[Abstract][Full Text]
Cepkova, M., Matthay, M. A.
(2006). Pharmacotherapy of Acute Lung Injury and the Acute Respiratory Distress Syndrome. J Intensive Care Med
21: 119-143
[Abstract]
Gattinoni, L., Caironi, P., Cressoni, M., Chiumello, D., Ranieri, V. M., Quintel, M., Russo, S., Patroniti, N., Cornejo, R., Bugedo, G.
(2006). Lung recruitment in patients with the acute respiratory distress syndrome.. NEJM
354: 1775-1786
[Abstract][Full Text]
Kacmarek, R. M., Wiedemann, H. P., Lavin, P. T., Wedel, M. K., Tutuncu, A. S., Slutsky, A. S.
(2006). Partial Liquid Ventilation in Adult Patients with Acute Respiratory Distress Syndrome. Am. J. Respir. Crit. Care Med.
173: 882-889
[Abstract][Full Text]
Ryter, S. W., Alam, J., Choi, A. M. K.
(2006). Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications. Physiol. Rev.
86: 583-650
[Abstract][Full Text]
Chan, A., Jayasuriya, K., Berry, L., Roth-Kleiner, M., Post, M., Belik, J.
(2006). Volutrauma activates the clotting cascade in the newborn but not adult rat. Am. J. Physiol. Lung Cell. Mol. Physiol.
290: L754-L760
[Abstract][Full Text]
Mols, G., Priebe, H.-J., Guttmann, J.
(2006). Alveolar recruitment in acute lung injury. Br J Anaesth
96: 156-166
[Abstract][Full Text]
Fan, E., Needham, D. M., Stewart, T. E.
(2005). Ventilatory Management of Acute Lung Injury and Acute Respiratory Distress Syndrome. JAMA
294: 2889-2896
[Abstract][Full Text]
Hager, D. N., Krishnan, J. A., Hayden, D. L., Brower, R. G., for the ARDS Clinical Trials Network,
(2005). Tidal Volume Reduction in Patients with Acute Lung Injury When Plateau Pressures Are Not High. Am. J. Respir. Crit. Care Med.
172: 1241-1245
[Abstract][Full Text]
Sakr, Y., Vincent, J.-L., Reinhart, K., Groeneveld, J., Michalopoulos, A., Sprung, C. L., Artigas, A., Ranieri, V. M., on behalf of the Sepsis Occurrence in Acutely Ill,
(2005). High Tidal Volume and Positive Fluid Balance Are Associated With Worse Outcome in Acute Lung Injury. Chest
128: 3098-3108
[Abstract][Full Text]
Levy, M. M.
(2005). Pathophysiology of Oxygen Delivery in Respiratory Failure. Chest
128: 547S-553S
[Abstract][Full Text]
MacIntyre, N. R.
(2005). Current Issues in Mechanical Ventilation for Respiratory Failure. Chest
128: 561S-567S
[Abstract][Full Text]
Rubenfeld, G. D., Caldwell, E., Peabody, E., Weaver, J., Martin, D. P., Neff, M., Stern, E. J., Hudson, L. D.
(2005). Incidence and outcomes of acute lung injury.. NEJM
353: 1685-1693
[Abstract][Full Text]
Bernard, G. R.
(2005). Acute Respiratory Distress Syndrome: A Historical Perspective. Am. J. Respir. Crit. Care Med.
172: 798-806
[Abstract][Full Text]
Tsuchida, S., Engelberts, D., Roth, M., McKerlie, C., Post, M., Kavanagh, B. P.
(2005). Continuous positive airway pressure causes lung injury in a model of sepsis. Am. J. Physiol. Lung Cell. Mol. Physiol.
289: L554-L564
[Abstract][Full Text]
Brewster, J. F, Graham, M. R., Mutch, W. A. C
(2005). Convexity, Jensen's inequality and benefits of noisy mechanical ventilation. J R Soc Interface
2: 393-396
[Abstract][Full Text]
Burns, S. M.
(2005). Mechanical Ventilation of Patients With Acute Respiratory Distress Syndrome and Patients Requiring Weaning: The Evidence Guiding Practice. Crit Care Nurse
25: 14-23
[Full Text]
Zupancich, E., Paparella, D., Turani, F., Munch, C., Rossi, A., Massaccesi, S., Ranieri, V. M.
(2005). Mechanical ventilation affects inflammatory mediators in patients undergoing cardiopulmonary bypass for cardiac surgery: A randomized clinical trial. J. Thorac. Cardiovasc. Surg.
130: 378-383
[Abstract][Full Text]
Krenitsky, J.
(2005). Adjusted Body Weight, Pro: Evidence to Support the Use of Adjusted Body Weight in Calculating Calorie Requirements. Nutr Clin Pract
20: 468-473
[Abstract][Full Text]
Trachsel, D., McCrindle, B. W., Nakagawa, S., Bohn, D.
(2005). Oxygenation Index Predicts Outcome in Children with Acute Hypoxemic Respiratory Failure. Am. J. Respir. Crit. Care Med.
172: 206-211
[Abstract][Full Text]
Kavanagh, B. P.
(2005). Prone Positioning in Children With ARDS: Positive Reflections on a Negative Clinical Trial. JAMA
294: 248-250
[Full Text]
Vlahakis, N. E., Hubmayr, R. D.
(2005). Cellular Stress Failure in Ventilator-injured Lungs. Am. J. Respir. Crit. Care Med.
171: 1328-1342
[Abstract][Full Text]
Myrianthefs, P. M., Briva, A., Lecuona, E., Dumasius, V., Rutschman, D. H., Ridge, K. M., Baltopoulos, G. J., Sznajder, J. I.
(2005). Hypocapnic but Not Metabolic Alkalosis Impairs Alveolar Fluid Reabsorption. Am. J. Respir. Crit. Care Med.
171: 1267-1271
[Abstract][Full Text]
Ghosh, S., Wilson, M. R., Choudhury, S., Yamamoto, H., Goddard, M. E., Falusi, B., Marczin, N., Takata, M.
(2005). Effects of inhaled carbon monoxide on acute lung injury in mice. Am. J. Physiol. Lung Cell. Mol. Physiol.
288: L1003-L1009
[Abstract][Full Text]
Stocchetti, N., Maas, A. I.R., Chieregato, A., van der Plas, A. A.
(2005). Hyperventilation in Head Injury: A Review. Chest
127: 1812-1827
[Abstract][Full Text]
Ciesla, D. J., Moore, E. E., Johnson, J. L., Burch, J. M., Cothren, C. C., Sauaia, A.
(2005). A 12-Year Prospective Study of Postinjury Multiple Organ Failure: Has Anything Changed?. Arch Surg
140: 432-440
[Abstract][Full Text]
Grasso, S., Fanelli, V., Cafarelli, A., Anaclerio, R., Amabile, M., Ancona, G., Fiore, T.
(2005). Effects of High versus Low Positive End-Expiratory Pressures in Acute Respiratory Distress Syndrome. Am. J. Respir. Crit. Care Med.
171: 1002-1008
[Abstract][Full Text]
Burleson, B. S., Maki, E. D.
(2005). Acute Respiratory Distress Syndrome. Journal of Pharmacy Practice
18: 118-131
[Abstract]
Wilson, M. R., Choudhury, S., Takata, M.
(2005). Pulmonary inflammation induced by high-stretch ventilation is mediated by tumor necrosis factor signaling in mice. Am. J. Physiol. Lung Cell. Mol. Physiol.
288: L599-L607
[Abstract][Full Text]
Lang, J. D., Figueroa, M., Sanders, K. D., Aslan, M., Liu, Y., Chumley, P., Freeman, B. A.
(2005). Hypercapnia via Reduced Rate and Tidal Volume Contributes to Lipopolysaccharide-induced Lung Injury. Am. J. Respir. Crit. Care Med.
171: 147-157
[Abstract][Full Text]
Hoste, E. A. J., Roosens, C. D. V. K., Bracke, S., Decruyenaere, J. M. A., Benoit, D. D., Vandewoude, K. H. D. K., Colardyn, F. A.
(2005). Acute Effects of Upright Position on Gas Exchange in Patients With Acute Respiratory Distress Syndrome. J Intensive Care Med
20: 43-49
[Abstract]
Previous
