What Is Acute Lung Injury?
1995; Elsevier BV; Volume: 107; Issue: 6 Linguagem: Inglês
10.1378/chest.107.6.1721
ISSN1931-3543
Autores Tópico(s)Neonatal Respiratory Health Research
Resumoacute lung injury diffuse alveolar damage The American Thoracic Society and the European Society of Intensive Care Medicine sponsored a meeting of leading investigators in 1992 to discuss key issues about ARDS. A summary of this group's deliberations was recently published in several principal journals relevant to pulmonary and critical care medicine.1Bernard GR Artigas A Brigham KL et al.The American-European Consensus conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination.Am J Respir Crit Care Med. 1994; 149: 818-824Crossref PubMed Scopus (5254) Google Scholar, 2Bernard GR Artigas A Brigham KL et al.Report of the American-European Consensus Conference on acute respiratory distress syndrome: definitions, mechanisms, relevant outcomes, and clinical trial coordination.J Crit Care. 1994; 9: 72-81Abstract Full Text PDF PubMed Scopus (326) Google ScholarBy its very nature, a consensus conference will produce compromise on controversial topics—why else is such a conference needed? A good example in this case was the “definition” of ARDS finally agreed on by the Consensus Committee. The Committee report declared that “the difficulty in determining the incidence and outcome of ARDS is largely due to the heterogeneity and lack of definitions for the underlying disease processes [and] the lack of definition for ARDS …” Accordingly, one of the explicitly stated goals of the Consensus Conference was to “bring clarity and uniformity to the definition of acute lung injury and ARDS.” Despite controversy (or maybe because of it), the Committee ultimately recommended that “acute lung injury” (ALI) be defined as “a syndrome of inflammation and increasing permeability that is associated with a constellation of clinical, radiologic, and physiologic abnormalities that cannot be explained by, but may coexist with, left atrial or pulmonary capillary hypertension,”1Bernard GR Artigas A Brigham KL et al.The American-European Consensus conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination.Am J Respir Crit Care Med. 1994; 149: 818-824Crossref PubMed Scopus (5254) Google Scholar, 2Bernard GR Artigas A Brigham KL et al.Report of the American-European Consensus Conference on acute respiratory distress syndrome: definitions, mechanisms, relevant outcomes, and clinical trial coordination.J Crit Care. 1994; 9: 72-81Abstract Full Text PDF PubMed Scopus (326) Google Scholar and that ARDS be defined simply as a more severe form of ALI.The rationale for this distinction seems obvious and reasonable: (1) not all patients with ALI are equally ill; ergo, some kind of stratification is needed to avoid focusing just on the most severely ill patients, on the one hand, or grouping patients with widely different degrees of illness on the other, and (2) patients with lesser degrees of injury might actually comprise a group that could be more responsive to new supportive or specific therapies.While no one could rationally argue against the intended benefits of clarity and uniformity, neither the definition offered by the Consensus Committee nor the criteria given for establishing the diagnosis (Fig 1) will achieve these ends. What follows is my attempt to justify this view.The Definitions of Ali and ARDSA “definition” should impart the “meaning or significance” of a phrase.3Random House Dictionary of the American Language. 2nd. Random House Publishers, New York1987: 983Google Scholar If we wish to define “acute lung injury,” we should first ask, what indeed is “injury”? One dictionary defines “injury” as “harm or damage that is done or sustained.”3Random House Dictionary of the American Language. 2nd. Random House Publishers, New York1987: 983Google Scholar Fortunately, in the context of acute lung injury, we already have a well-described set of observations (termed “diffuse alveolar damage” [DAD]) that are widely accepted as the histopathologic correlate of ARDS (Table 1).4Crouch E Pathobiology of pulmonary fibrosis.Am J Physiol. 1990; 3: L159-L184Google Scholar, 5Katzenstein ALA Askin FB Surgical pathology of non-neoplastic lung disease. WB Saunders, Philadelphia1990: 9-57Google Scholar The “harm,” however, that is done by some form of damage to the lung is simply a deterioration in lung function.Table 1Pathology of Diffuse Alveolar DamageAbnormal FindingsAlveolar epithelial cell necrosisInflammatory cell infiltrationProteinaceous alveolar and interstitial edemaAlveolar hyaline membranesType II pneumocyte proliferation (later)Varying degrees of intra-alveolar and interstitial fibrosis (occurs late in course, if at all) Open table in a new tab Since the lungs’ principal function is gas exchange, measures of oxygenation (or even CO2 elimination) are certainly valid markers of dysfunction. Unfortunately, these are nonspecific markers; disturbances in gas exchange usually represent the sum total effect of numerous processes (Fig 2). They are not just the manifestation of alveolar damage per se. There is an important link, of course, between the development of DAD and the disturbance in gas exchange, namely the development of proteinaceous alveolar edema, which itself is principally the result of increased vascular permeability to plasma solutes and water (Fig 2).Figure 2Schematic development of hypoxemia (↓ PaO2) and reduced respiratory system compliance (Crs) as a result of acute lung injury. The bold arrows indicate the principal pathway. At each step, however, other processes—directly related, indirectly related, or unrelated—can mimic or exacerbate the changes due to lung injury per se. PMB=vascular permeability; EVLW=extravascular lung water; Pc, Pv, Pw=hydrostatic pulmonary capillary, venous, or wedge pressures, respectively; πc=oncotic pressure; △rPBF=change in regional pulmonary blood flow pattern. “Lymph” refers to lymphatic drainage as well as all other modes of EVLW resolution.View Large Image Figure ViewerDownload (PPT)So here we now have the necessary ingredients for a meaningful definition of ALI and ARDS (Table 2): Lung injury is present when characteristic pathologic abnormalities in the lungs’ normal underlying structure result in a deterioration of normal lung function, and, ARDS is a specific form of lung injury with diverse causes, characterized pathologically by diffuse alveolar damage, and pathophysiologically by a breakdown in both the barrier and gas exchange functions of the lung, resulting in proteinaceous alveolar edema and hypoxemia.Table 2Proposed Definitions of ALI and ARDSAcute Lung Injury:Any significant deterioration in lung function due to characteristic pathologic abnormalities in the lungs’ normal underlying structure or architecture.ARDS:A specific form of injury with diverse causes, characterized pathologically by diffuse alveolar damage, and pathophysiologically by a breakdown in both the barrier and gas exchange functions of the lung, resulting in proteinaceous alveolar edema and hypoxemia. Open table in a new tab This definition of lung injury links structural changes with functional abnormalities; the exact nature of the structural or functional defect can vary depending on the condition being examined. In the case of ARDS, the structural problem is manifested as DAD, while the functional problem is the breakdown in the normal endothelial barrier.Note that with this definition of ALI and ARDS, we do not need (yet) to consider any particular criteria for diagnosis: not the PaO2/FIo2 threshold that must be breached, not the level of PEEP that may or may not be allowed, and not whether patients with heart failure or volume overload should be arbitrarily excluded. Further, there is no need to appropriate the term “lung injury” only for patients with ARDS or even “mild” ARDS. And there is no need to create distinctions about lung injury and ARDS based on arbitrary thresholds of supposed severity.Some might argue that since pulmonary edema can resolve quickly in some patients, eg, heroin-induced pulmonary edema, near-drowning, tocolytic associated pulmonary edema, it is unlikely that they have the same abnormality, ie, DAD, as those who develop ARDS in association with sepsis or aspiration. I would counter that not only are these cases uncommon, but we do not really know the pathology of these rapidly resolving examples of ALI. So, we also do not know whether they are examples of “mild” DAD or of no DAD at all. My position would be that if such syndromes did not involve DAD, they should not be classified as ARDS. Instead, they should be classified as some alternative form of ALI (with its own expected natural history) or even more nonspecifically, as simply a form of noncardiogenic pulmonary edema.Criteria for ALI/ARDSThe definitions proposed in Table 2 are meaningful, I believe, because they tell us what we must demonstrate, ie, what criteria are necessary, for a definitive diagnosis of ARDS: (1) diffuse, ie, bilateral, nonfocally distributed, alveolar edema; (2) significantly increased pulmonary vascular permeability; and (3) “diffuse alveolar damage” pathologically.These criteria, while definitive, are admittedly impractical (obviously, obtaining lung tissue for microscopic examination in every case of suspected ARDS is out of the question). However, if alternative criteria are to be used, the standard for accepting them should be how well they predict the presence of any or all of these definitive criteria (Table 3).Table 3Proposed “Definitive” Criteria for the Diagnosis of ARDS •diffuse (bilateral) alveolar edema•increased lung vascular permeability•diffuse alveolar damage pathologically Open table in a new tab How do the suggested criteria of the Consensus Conference (Fig 1) stack up against this standard? Not very well. With the Consensus Conference criteria, the onset of the syndrome must be acute. Therefore, patients who develop proteinaceous alveolar edema and diffuse alveolar damage over several days (2?, 3?, longer?) should be excluded. I suspect that in some studies and in some centers they are, while in others they are not. Further, patients with pulmonary inflammation and increased vascular permeability (the Consensus Conference “definition” of ALI) who also have a wedge pressure >18 mm Hg will be excluded. Why? And where are the data that link a particular PaO2/FIo2 to predictable structural changes in the alveolo-capillary membrane, to the development of permeability edema, or to the amount of edema that accumulates as a result of increased vascular permeability? It does not exist; nor would we expect it to, given the physiology schematized by Figure 2.In the experimental laboratory, a measure of vascular permeability is probably the most commonly used method of identifying lung injury. For this discussion, noninvasive nuclear medicine techniques are now available for such evaluations at the bedside of patients with ARDS.6Byrne K Sugerman HJ Experimental and clinical assessment of lung injury by measurement of extravascular lung water and transcapillary protein flux in ARDS: a review of current techniques.J Surg Res. 1988; 44: 185-203Abstract Full Text PDF PubMed Scopus (24) Google Scholar, 7Kaplan JD Calandrino FS Schuster DP A positron emission tomographic comparison of pulmonary vascular permeability during the adult respiratory distress syndrome and pneumonia.Am Rev Respir Dis. 1991; 143: 150-154Crossref PubMed Scopus (41) Google Scholar, 8Putensen C Mutz N Himmer G et al.Gamma scintigraphic imaging of lung microvascular permeability in adult respiratory distress syndrome.Crit Care Med. 1990; 18: 807-812Crossref PubMed Scopus (9) Google Scholar The theory, mathematics, and limitations of such methods are well understood.9Roselli RJ Harris TR Lung fluid and macromolecular transport.in: Chang HK Respiratory physiology: an analytical approach. Marcel Dekker, New York1989: 633-735Google Scholar, 10Peterson BT Permeability: theory vs practice in lung research.Am J Physiol. 1992; 262: L243-L256PubMed Google Scholar, 11Mintun MA Warfel TE Schuster DP Evaluating pulmonary vascular permeability with radiolabeled proteins: an error analysis.J Appl Physiol. 1990; 68: 1696-1706PubMed Google Scholar, 12Roselli JR Riddle WR Analysis of noninvasive macromolecular transport measurements in the lung.J Appl Physiol. 1989; 67: 2343-2350PubMed Google Scholar When used in clinical studies, these methods consistently differentiate high-pressure pulmonary edema from that associated with ALI.6Byrne K Sugerman HJ Experimental and clinical assessment of lung injury by measurement of extravascular lung water and transcapillary protein flux in ARDS: a review of current techniques.J Surg Res. 1988; 44: 185-203Abstract Full Text PDF PubMed Scopus (24) Google Scholar, 7Kaplan JD Calandrino FS Schuster DP A positron emission tomographic comparison of pulmonary vascular permeability during the adult respiratory distress syndrome and pneumonia.Am Rev Respir Dis. 1991; 143: 150-154Crossref PubMed Scopus (41) Google Scholar, 13Spicer KM Reines DH Frey GD Diagnosis of adult respiratory distress syndrome with Tc-99m human serum albumin and portable probe.Crit Care Med. 1986; 14: 669-676Crossref PubMed Scopus (15) Google Scholar A limited set of data indicates that they can track the natural history of lung injury.8Putensen C Mutz N Himmer G et al.Gamma scintigraphic imaging of lung microvascular permeability in adult respiratory distress syndrome.Crit Care Med. 1990; 18: 807-812Crossref PubMed Scopus (9) Google Scholar, 14Calandrino JS Anderson DJ Mintun MA et al.Pulmonary vascular permeability during the adult respiratory distress syndrome.Am Rev Respir Dis. 1988; 138: 421-428Crossref PubMed Scopus (53) Google Scholar, 15Byrne K Tatum JL Henry DA et al.Increased morbidity with increased pulmonary albumin flux in sepsis-related adult respiratory distress syndrome.Crit Care Med. 1992; 20: 28-32Crossref PubMed Scopus (26) Google Scholar And a critical point, I think, is that there is at least some evidence that such measures are predictive of the underlying pathologic alveolar damage that is their cause,16Velazquez M Weibel ER Kuhn C et al.PET evaluation of pulmonary vascular permeability: a structure-function correlation.J Appl Physiol. 1991; 70: 2206-2216PubMed Google Scholar unlike any other proposed index of injury (gas exchange, mechanics, lung water accumulation, etc).If measures of vascular permeability do indeed correlate with the severity of pathologic damage (and additional study is needed to verify this inference), then a more “practical” set of criteria can be proposed for the diagnosis of ARDS (Table 4): (1) bilateral, nonfocally distributed radiographic infiltrates consistent with alveolar edema; (2) significantly increased vascular permeability (until more complete information is available, a fourfold to fivefold increase over normal values; alternatively, >2 SD from the normal population mean), and (3) an appropriate clinical setting, ie, the classic clinical “risk factors” for the development of ARDS. The reason for the addition of the third criterion is that increased vascular permeability is itself a nonspecific marker of inflammatory damage to the alveolo-capillary interface (Fig 3).7Kaplan JD Calandrino FS Schuster DP A positron emission tomographic comparison of pulmonary vascular permeability during the adult respiratory distress syndrome and pneumonia.Am Rev Respir Dis. 1991; 143: 150-154Crossref PubMed Scopus (41) Google ScholarTable 4Proposed “Practical” Criteria for the Diagnosis of ARDS •radiographic infiltrates consistent with diffuse (bilateral) alveolar edema•significantly increased vascular permeability*Until more complete information is available, a four- to fivefold increase over normal values; alternatively >2 S.D. from the normal population mean.•appropriate clinical setting* Until more complete information is available, a four- to fivefold increase over normal values; alternatively >2 S.D. from the normal population mean. Open table in a new tab Figure 3The pulmonary transcapillary escape rate (PTCER), an index of vascular permeability, in a variety of patient groups, as previously reported.7Kaplan JD Calandrino FS Schuster DP A positron emission tomographic comparison of pulmonary vascular permeability during the adult respiratory distress syndrome and pneumonia.Am Rev Respir Dis. 1991; 143: 150-154Crossref PubMed Scopus (41) Google Scholar, 14Calandrino JS Anderson DJ Mintun MA et al.Pulmonary vascular permeability during the adult respiratory distress syndrome.Am Rev Respir Dis. 1988; 138: 421-428Crossref PubMed Scopus (53) Google Scholar,34Kaplan JD Trulock EP Anderson DJ et al.Pulmonary vascular permeability in interstitial lung disease: a positron emission tomography.Am Rev Respir Dis. 1992; 145: 1495-1498Crossref PubMed Scopus (20) Google Scholar, 35Kaplan JD Trulock EP Cooper JD et al.Pulmonary vascular permeability after lung transplantation: a positron emission tomographic study.Am Rev Respir Dis. 1992; 145: 954-957Crossref PubMed Google Scholar, 36Kaplan JD Calandrino FS Schuster DP Effect of smoking on pulmonary vascular permeability: a positron emission study.Am Rev Respir Dis. 1992; 145: 712-715Crossref PubMed Scopus (6) Google Scholar Note that PTCER is in the same range of values as measured in normal subjects in the following groups of subjects: in smokers without acute illness; clinically inactive interstitial lung disease; in lung allografts (alio) in patients without clinical rejection (Rej) postlung transplantation (LT). PTCER is not significantly different from normal in patients with congestive heart failure (CHF). It is highest in patients with ARDS and in lung regions with lobar pneumonia. Other patient populations have intermediate values.View Large Image Figure ViewerDownload (PPT)How abnormal must pulmonary vascular permeability be before it reliably predicts the presence of DAD in the appropriate clinical setting? The answer is not known. Based on data presented in Figure 3 and reference 16, I think values four to five times the mean population norm would be a reasonable place to start—but this is basically a guess. Again, more direct information is needed.Must a clinician obtain a measurement of vascular permeability to make the diagnosis of ARDS or to treat suspected patients accordingly? Of course not. As long as treatment remains “supportive,” the need for a definitive diagnosis is reduced. But for investigators participating in clinical trials, the need for definitive diagnosis is another matter. Except for cost, I see no reason to avoid making these measurements in clinical studies. Unless and until some other index is shown to satisfactorily predict the presence of DAD (see below), the standard must be a measure of abnormal vascular permeability associated with alveolar edema in the appropriate clinical setting. I hope that the newly formed National Institutes of Health-sponsored network of clinical centers to study new therapies for ARDS will seriously consider including such measurements in any of their contemplated trials.Does it Matter?This squabbling about definitions and criteria might seem largely irrelevant to many since no specific therapy exists for ARDS. An intriguing problem has recently emerged, however, and it can only be resolved once such issues are finally settled. In Figure 4, I have plotted the reported mortality in most of the major large epidemiologic or therapeutic trials of ARDS during the past 25 years.17Suchyta MR Clemmer TP Elliott CG et al.The adult respiratory distress syndrome: a report of survival and modifying factors.Chest. 1992; 101: 1074-1079Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar, 18Suchyta MR Clemmer TP Orme JF et al.Increased survival of ARDS patients with severe hypoxemia (ECMO criteria).Chest. 1991; 99: 951-955Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar, 19Bell RC Coalson JJ Smith JD et al.Multiple organ system failure and infection in adult respiratory distress syndrome.Ann Intern Med. 1983; 99: 293-298Crossref PubMed Scopus (436) Google Scholar, 20Montgomery AB Stager MA Carrico CJ et al.Causes of mortality in patients with the adult respiratory distress syndrome.Am Rev Respir Dis. 1985; 132: 485-489PubMed Google Scholar, 21Sloane PJ Gee MH Gottlieb JE et al.A multicenter registry of patients with acute respiratory distress syndrome: physiology and outcome.Am Rev Respir Dis. 1992; 146: 419-426Crossref PubMed Scopus (239) Google Scholar, 22Fowler AA Hamman RF Zerbe GO et al.Adult respiratory distress syndrome: prognosis after onset.Am Rev Respir Dis. 1985; 132: 472-478PubMed Google Scholar, 23Villar J Slutsky AS The incidence of the adult respiratory distress syndrome.Am Rev Respir Dis. 1989; 140: 814-816Crossref PubMed Scopus (162) Google Scholar, 24Morris AH Wallace CJ Menlove RL et al.Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome.Am J Respir Crit Care Med. 1994; 149: 295-305Crossref PubMed Scopus (749) Google Scholar, 25Bone RC Fisher CJ Clemmer TP et al.Early methylprednisolone treatment for septic syndrome and the adult respiratory distress syndrome.Chest. 1987; 92: 1032-1036Crossref PubMed Scopus (288) Google Scholar, 26Bone RC Slotman G Maunder R et al.Randomized double-blind, multicenter study of prostaglandin E1 in patients with the adult respiratory distress syndrome.Chest. 1989; 96: 114-119Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar, 27Bernard GR Luce JM Sprung CL et al.High-dose corticosteroids in patient with the adult respiratory distress syndrome.N Engl J Med. 1987; 317: 1565-1570Crossref PubMed Scopus (710) Google Scholar, 28Zapol WM Snider MT Hill JD et al.Extracorporeal membrane oxygenation in severe acute respiratory failure.JAMA. 1979; 242: 2193-2196Crossref PubMed Scopus (1167) Google Scholar, 29Anzueto A Baughman R Guntupalli K et al.An interventional, randomized, placebo-controlled trial evaluating the safety and efficacy of aerosolized surfactant in patients with sepsis-induced ARDS.Am Rev Respir Dis. 1994; 149: A567Crossref Scopus (42) Google Scholar Note that for much of this period, mortality was indeed in the oft-quoted 50 to 70% range for ARDS. Yet, as Figure 4 implies, the mortality of ARDS has been steadily decreasing, a trend first noted by Utah investigators.17Suchyta MR Clemmer TP Elliott CG et al.The adult respiratory distress syndrome: a report of survival and modifying factors.Chest. 1992; 101: 1074-1079Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar, 18Suchyta MR Clemmer TP Orme JF et al.Increased survival of ARDS patients with severe hypoxemia (ECMO criteria).Chest. 1991; 99: 951-955Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar The current bench mark, it seems, should be nearer to 40%29Anzueto A Baughman R Guntupalli K et al.An interventional, randomized, placebo-controlled trial evaluating the safety and efficacy of aerosolized surfactant in patients with sepsis-induced ARDS.Am Rev Respir Dis. 1994; 149: A567Crossref Scopus (42) Google Scholar than 70%.Figure 4Reported mortalities for ARDS in the following studies: 1 is reference 28; 2 is reference 37; 3 is reference 19; 4 is reference 20; 5 is reference 22; 6 is reference 27; 7 is reference 25; 8 is reference 26; 9 is reference 23; 10 is reference 18; 11 is reference 17; 12 is reference 21; 13 is reference 29; 14 is reference 24.View Large Image Figure ViewerDownload (PPT)What could account for such a dramatic drop in mortality? Only three possibilities seem viable: (1) the “virulence” of ARDS itself has decreased (unlikely); (2) the patient populations are different in the different studies (obviously possible); or (3) numerous changes in supportive therapy have had small but additive effects, finally culminating in measurable differences in survival. Which therapies might have made a difference? No one can say since none have been formally tested, but consider this list of possibilities: better and more aggressive management of shock, better fluid management, more aggressive nutritional management, improved ventilator support with reduced airway pressures, virtual elimination of high-dose steroid use in the first few days of the syndrome, greater use of steroids in patients with ventilator dependence during the fibroproliferative phase, more aggressive surveillance, and treatment of associated nosocomial infection, and so on.The trend in Figure 4 could, of course, be an artifact of different patient populations. If all the studies shown in Figure 4 had used the Consensus Conference criteria (Fig 1) as inclusion criteria, would we know the answer? Apparently not, since analyses by the University of Utah group17Suchyta MR Clemmer TP Elliott CG et al.The adult respiratory distress syndrome: a report of survival and modifying factors.Chest. 1992; 101: 1074-1079Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar, 18Suchyta MR Clemmer TP Orme JF et al.Increased survival of ARDS patients with severe hypoxemia (ECMO criteria).Chest. 1991; 99: 951-955Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar clearly suggest that mortality has decreased despite similar “criteria.”To know if these patient populations are similar (or different), one must have not only a well-defined set of threshold inclusion criteria, but also a set of clinically appropriate tests that quantify the severity of ARDS. Indeed, in this case, we need not one, but two indexes of severity: one that would measure the severity of ALI per se, and one that would measure the overall severity of the patient's illness. The latter should quantify the patient's response to the injury and should incorporate in some meaningful way the context within which the illness develops, ie, comorbidities and underlying illnesses.The rationale for two severity indexes is clear: to answer a question about whether a new treatment for lung injury is effective, one needs a measure that quantifies the severity of the injury itself; to resolve whether a new treatment is worth whatever costs are associated with it, one needs a more global marker, such as mortality.Most indexes of lung injury are, not surprisingly, poor predictors of mortality; there are just too many associated problems, comorbidities, associated illness, premorbid health, etc, in such patients for any lung injury index to be held to such a standard. Rather, the standard should not be whether these indexes can accurately predict mortality, but whether they can accurately quantify lung injury. To predict mortality, more generalized systems, such as APACHE III, the Simplified Acute Physiology Score, the Mortality Prediction Model, or even a simple organ-system failure score, may be more appropriate.30Kollef MH Schuster DP Predicting intensive care unit outcome with scoring systems.Crit Care Clin. 1994; 10: 1-18PubMed Google Scholar, 31Knaus WA Wagner DP Draper EA et al.The APACHE III prognostic system: risk prediction of hospital mortality for critically ill hospitalized adults.Chest. 1991; 100: 1619-1636Abstract Full Text Full Text PDF PubMed Scopus (3028) Google Scholar However, the direct and proximate link between the development of diffuse alveolar damage and the severity of changes in vascular permeability (Fig 2)16Velazquez M Weibel ER Kuhn C et al.PET evaluation of pulmonary vascular permeability: a structure-function correlation.J Appl Physiol. 1991; 70: 2206-2216PubMed Google Scholar make it at least credible that a measure of vascular permeability might not only be useful in some threshold sense as a criterion for ARDS, but could also be used to quantify its severity as well.Until now, the most common method to quantify lung injury has been the lung injury score of Murray et al,32Murray VF Mathay MA Luce JM et al.Pulmonary perspectives: an expanded definition of the adult respiratory distress syndrome.Am Rev Respir Dis. 1988; 138: 720-723Crossref PubMed Scopus (2028) Google Scholar even though there are virtually no independent data to support its validity for this purpose. Interestingly, in a very recent report involving only 14 patients, Sinclair et al33Sinclair DG Braude S Haslam PL et al.Pulmonary endothelial permeability in patients with severe lung injury: clinical correlates and natural history.Chest. 1994; 106: 535-539Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar showed a significant correlation between the lung injury score and bedside measurements of lung vascular permeability (albeit, with very wide 95% confidence intervals). While they concluded that their data suggest that “increased permeability of the alveolar capillary membrane is the fundamental abnormality … affecting the four variables that make up the clinically derived [lung injury score],” their data—if corroborated in a much larger group of patients—also suggest that the easily obtained lung injury score could eventually be used instead of direct measurements of vascular permeability as an index of injury.To summarize, the definition of ARDS should not depend on any single arbitrary dichotomizing measurement, whether it be oxygenation, vascular permeability, or any other scaler. Rather, ARDS should be defined as a specific form of lung injury, characterized pathologically by diffuse alveolar damage, and
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