ACUTE RESPIRATORY DISTRESS SYNDROME

UNDERSTANDING PATHOPHYSIOLOGY AND MANAGEMENT a historical review

Ubaidur Rahaman Senior Resident, CCM, SGPGIMS Lucknow, India

A Treatise on Diseases of the Chest Laennec, 1821

idiopathic anasarca of the lungs; pulmonary edema without heart failure

PROBABLY FIRST PUBLISHED SCINTIFIC DISCRIPTION

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

What's in a name? That which we call a rose by any other name would smell as sweet.
-William Shakespeare

Double pneumonia - till mid 1900s Post-traumatic massive pulmonary collapse- WW I Traumatic wet lung- WW II Shock lung - Korea early 1950s Da Nang lung / ventilator lung- Vietnam war late 1960s Capillary leak syndrome Acute alveolar syndrome Post perfusion lung Congestive atelectasis Adult hyaline membrane disease
Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

Acute respiratory distress in adults. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. 1967, Lancet 2:319-323
Case series of 12 patients presenting with acute respiratory distress, cyanosis refractory to oxygen therapy, decreased lung compliance and diffuse pulmonary infiltrates on chest x-ray.

AUTOPSY
lungs were heavy (average 2110 g), microscopic examination Revealed areas of alveolar atelectasis, interstitial and alveolar hemorrhage and edema, dilated and congested capillaries

ACUTE RESPIRATORY DISTRESS SYNDROME The adult respiratory distress syndrome: clinical features, factors influencing prognosis and principles of management.
Petty TL, Ashbaugh DG, Chest 1971;60:233239.

An expanded definition of the adult respiratory distress syndrome.

Murray JF, Matthay MA, Luce JM, Flick MR. Am Rev Respir Dis 1988; 138:720723.

lung injury scoring system (LIS)

Oxygenation, Positive end-expiratory pressure Respiratory system compliance Chest radiograph
NO LUNG INJURY-------------0 MILD TO MODERATE INJURY------0.1-2.5 SEVERE LUNG INJURY (ARDS)---- >22.5

Addition of objective criteria- PEEP and Compliance

The American European consensus conference on ARDS: definitions mechanisms, relevant outcomes and clinical trial coordination.
Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R.

Am J Respir Crit Care Med.1994;149:818824.

Acute lung injury ( ALI) ARDS subset of ALI with severe hypoxaemia Acute onset CXR- bilateral infiltrates consistent with pulmonary oedema Ppaw 18 mmHg or absence of clinical evidence of left atrial hypertension, ALI - PaO2/FIO2 300 ; ARDS PaO2/FIO2 200.

Definition was made broad intentionally to encompass different types of AHRF occurring in variety of settings

Problem CXR interpretation subjective P/F affected by level of PEEP Requirement of PAC- interpretation- Ppao may be higher in absence of CHF

Development of a clinical definition for acute respiratory distress syndrome using the delphi technique. Ferguson ND, Davis AM, Slutsky AS, Stewart TE. J Crit Care. 2005;20:147-154

Delphi criteria
1 2 3 4 5 Hypoxaemia Acute onset CXR Non cardiogenic origin Decreased lung compliance Predisposition PaO2/ FiO2 200 mmHg with PEEP 10 Rapid onset 72 hours Bilateral airspace disease 2 quadrants on frontal CXR No clinical e/o CHF including use of PAC and/or echo Cs res syst <50 ml/cmH2O ( with patient sedated, VT= 8 ml/kg IBW, PEEP 10 Direct and or indirect factor associated with lung injury

ARDS- presence of criteria 1-4 + one of 5 or 6

Development of a clinical definition for acute respiratory distress syndrome using the delphi technique. Ferguson ND, Davis AM, Slutsky AS, Stewart TE. J Crit Care. 2005;20:147-154

Airspace disease- presence of one or more of following1. 2. 3. 4. Air bronchogram Acinar shadows- nodular opacities 4-10 mm diam with poor margination Coalescence of acinar shadows Silhouette sign- loss of def of heart border or hemidiaphragm, excluding that caused by lobar collapse

Ubaidur Rahaman, Senior Resident, CCM, SGPGIMS, Lucknow, India Rahaman, Lucknow,

1970 to mid 1980s

Acute respiratory distress in adults. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. 1967, Lancet 2:319-323
Case series of 12 patients presenting with acute respiratory distress, cyanosis refractory to oxygen therapy, decreased lung compliance and diffuse pulmonary infiltrates on chest x-ray. AUTOPSY lungs were heavy (average 2110 g), microscopic examination revealed areas of alveolar atelectasis, interstitial and alveolar hemorrhage and edema, dilated and congested capillaries

ARDS LUNG IS HOMOGENOUSLY HEAVY AND STIFF

requiring high inflation pressure to ventilate

How to treat

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

This Weeks Citation Classic OCTOBER 29, 1979 Ashbaugh D G, Petty T L, Bigelow D B & Harris T M. Continuous positive-pressure breathing (CPPB) in adult respiratory distress syndrome. J. Thorac. Cardiovas. Surg. 57:31-41, 1969
The first patient in which we observed acute respiratory distress was a 29-year-oldman involved in an automobile accident who, despite being placed on a respirator, went on to develop severe and progressive respiratory failure and died within 48 hours. Our failure, in what we felt should have been a salvageable case, stimulated us to look for additional cases. A few weeks after our first case, a 12-year-old boy was admitted with a severe crushing chest injury. He too, began to follow a similar downhill course despite a tracheotomy and being placed on our only volume respirator, an Engstrom. Even with large volumes of air and 100% oxygen he was doing poorly.

In desperation it was decided to try adding

which happened to be a feature of that model of Engstrom respirator

end expiratory pressure,

Dramatic improvement occurred in the patients condition and he eventually went on to make a very good recovery. Several additional patients were then seen and treated with varying results
Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

The first ENLIGHTENMENT

Positive End Expiratory Pressure

Acute respiratory distress in adults.

Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. 1967, Lancet 2:319-323

Mile stone paper- initially rejected by 3 major US journals 12 patients with ARDS of pulmonary and extra- pulmonary origin, some with fluid overload and shock.

PEEP was applied in five of them (three survived) ZEEP was applied in seven (two survived). PEEP was described as a buying time maneuver, preventing alveolar collapse at end-expiration.

The adult respiratory distress syndrome: Clinical features, factors influencing prognosis and principles of management.
Petty TL, Ashbaugh DG, Chest 1971;60:233239. ETIOLOGY diffuse pulmonary injuries, direct or indirect, of lung parenchyma exudation of fluid and loss of surfactant activity impaired gas exchange and reduced pulmonary compliance

Outcome dependent on 1. Degree of original injury 2. Effectiveness of respiratory support 3. Prevention of further pulmonary injury

MANAGEMENT PRINCIPLE

Prevent alveolar collapse and maintain oxygenation

Volume respirator Oxygen control PEEP

Prevent further injury

Oxygen control Fluid restriction Antibiotics for specific infections Corticosteroid drugs

HOW PEEP HELPS IN IMPROVING OXYGENATION? Ventilation with end expiratory pressure in acute lung disease.
Falke KJ, Pontoppidan H, Kumar A, Leith DE, Geffin B, Laver MB. J Clin Invest, 1972, 51:2315-2323

effects of PEEP in 10 patients with severe acute respiratory failure when IPPV with Fio2 up to 0.5 failed to maintain PaO2 70 torr. PEEP of 0, 5, 10 and 15 cm H20 were applied for 30-min Gas exchange, lung volumes, compliance, and hemodynamics- studied at each level of PEEP FRC and PaO2 rose linearly with level of PEEP; Pao2 and FRC showed a close correlation. Lung compliance increased with lower PEEP- RECRUITMENT, decreased with higher PEEP OVERDISTENSION Surprisingly increase in PaO2 may go along with fall in compliance* C.I. fell in some patients and rose in others and there was no correlation with level of PEEP. The most probable explanation for the effect of PEEP on PaO2 and compliance is recruitment of gas exchange airspaces and prevention of terminal airway closure.

*recruitment and overdistension of alveoli may take place simultaneously.

WHAT LEVEL OF PEEP? is their any OPTIMUM PEEP

Optimum end-expiratory airway pressure in patients with acute pulmonary failure. Suter PM, Fairley B, Isenberg. N Engl J Med, 1975; 292:284289

ventilation within the range of pulmonary pressure/ volume range associated with maximum compliance negative effect of PEEP on CO is minimum.

Optimum PEEP- best PaO2 with best oxygen transport ( C.O.) Associated with highest compliance of respiratory system compliance Recruitment prevails over overdistension.

WHAT LEVEL OF PEEP? is their any OPTIMUM PEEP

High level positive end expiratory pressure (PEEP) in acute respiratory insufficiency
Kirby RR, Downs JB, Civetta. Chest;1975; 67:156163

SUPER PEEP concept- pressure that maximally reduces the shunt ( 20% at PaO2 20 torr)

Gas exchange, static pressure volume curve and positive-pressure ventilation at the end of expiration. Study of 16 cases of acute respiratory insufficiency in adults.
Lemaire F, Harf A, Simonneau G. Ann Anesthesiol, 1981, Fr 22:435441

Minimal PEEP- 2 cmH2O above the LIP on inflation limb of PV curve

SUMMARY
ARDS lung is homogenously heavy and stiff Treat with high tidal volume and pressure to tackle high PaCO2 Apply high PEEP- ?optimum PEEP to improve oxygenation Recognize side effects is barotrauma, Beware of hemodynamic impairment due to PEEP

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

Mid 1980s era of computed tomography Concept of baby lung

Preservation of Normal Lung Regions in the Adult Respiratory Distress Syndrome Analysis by Computed Tomography Richard J. Maunder, W P. Shuman, et sl. JAMA 1986;255:2463-2465)

Despite appearance of diffuse, symmetric involvement by standard CXR CT images demonstrate sparing of substantial portion of lung parenchyma, lack of homogeneity and tendency toward posterior involvement on CT images

L Gattinoni, A Presenti et al

22 patients with acute respiratory failure Lung CT and physiological measurement at 5, 10 and 15 cmH2O PEEP Investigated for relationship between morphology and physiology Lung densities were concentrated in dependent regions Average lung weight was increased twofold above normal Excess lung weight correlated with mean Pulmonary artery pressure Venous admixture correlated with non-inflated tissue mass

Increasing PEEP Progressive clearing of densities and increased mass of normally aerated tissue (Recruitment) Reduction of venous admixture

L Gattinoni, A Presenti et al

ARDS: the non-homogeneous lung; facts and hypothesis

Gattinoni L, Pesenti A,Intensive Crit Care Dig. 1987;6:14

ARDS lung is non homogenous with densities concentrated in most dependent regions Amount of normally aerated tissue at end expiration was about 200-500 gm in severe ARDS: dimension of the lung of a 5-6 years old child ARDS LUNG IS A BABY LUNG not STIFF LUNG This baby lung is a healthy anatomical structure, located in the non dependent regions. Respiratory compliance well correlated with the amount of the normally aerated tissue only

The second ENLIGHTENMENT

ARDS lung non homogenous and BABY not STIFF Elasticity of this baby lung is nearly normal

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

We were ventilating the lung of a healthy child with about 1000ml of VT causing more damage then benefit

CAN IT BE PREVENTED & HOW

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

Small healthy aerated tissue in non dependent region with poor perfusion can making it dependent help?

PRONE Ventilation

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

The prone position in ARDS patients. A clinical study.

Langer M, Mascheroni D, Marcolin R, Gattinoni L. Chest, 1988; 94:103107

13 moderate-severe ARDS patients proned for 2 hours.

The gas exchange and hemodynamics were evaluated before, during, and after proning CT was obtained in both the supine and prone positions in two of these patients Responder- Pa02 increase 10 mm Hg after 30 minutes of proning

CT in prone position disappearance of posterobasal densities and appearance of new densities in the anterior regions

..continued

The prone position in ARDS patients. A clinical study.

Langer M, Mascheroni D, Marcolin R, Gattinoni L. Chest, 1988; 94:103107

Baby lung in not healthy anatomical structure but functional concept

Redistribution of densities after proning

Early 90s Concept of sponge lung

Vertical gradient of regional lung inflation in adult respiratory distress syndrome.

Pelosi P, DAndrea L, Vitale G. Am J Respir, 1994; Crit Care Med 149:813

Superimposed pressure

edema fluid is evenly distributed from sternum to vertebra Increased lung weight due to accumulated edema raises hydrostatic pressure through out the lung Gas in dependent lung regions is squeezed out by heavy lung parenchyma above

Generalized, not regional involvement Densities are in fact due to loss of alveolar gases, not due to increase edema

ARDS LUNG IS SPONGE LUNG The ARDS Lung. New insights from compute tomography, Bone; JAMA, 1993, 269 (16): 2134-2135

Sponge lung explains Redistribution of densities in prone position Mechanism of PEEP

ARDS lung is both baby and sponge

SUMMARY

Baby lung is actually small lung open at end expiration

It may become larger during inspiration due to newly recruited tissue Baby lung is not healthy but aerated

Smaller the baby lung the greater the potential for VILI

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

The third ENLIGHTENMENT

Protective lung ventilation

CONCEPT OF

Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome.
Hickling KG, Henderson SJ, Jackson R. Intensive Care Med. 1990;16(6):372-7.

50 patients LIS 2.5, mean PaO2/FiO2 = 94 managed with low tidal volume, disregarding hypercapnia

hospital mortality was significantly lower than predicted. Only one death was due to respiratory failure, caused by pneumocystis pneumonia. 10 patients had a "ventilator score" greater than 80, which has previously predicted 100% mortality from respiratory failure. Only 2 died, neither from respiratory failure.

The true ENLIGHTENMENT was not the use of low tidal volume but the CHANGE OF GOAL

NORMAL OXYGENATION AND VENTILATION ( PaCO2)

ADEQUATE OXYGENATION AND PERMISSIVE HYPERCAPNIA

.The concept of "baby lung". Gattinoni L, Pesenti A. Intensive Care Med. 2005 Jun;31(6):776-84. Epub 2005 Apr 6

Much has been said about end expiratory pressure What happens at end inspiration: concept of recruitment

During inspiration only part of the lung is recruited Opening pressures are widely and normally distributed throughout lung parenchyma Some lung regions usually most dependent may require higher opening pressure If the Pplat is limited, collapsed tissues with higher opening pressure stay closed throughout the respiratory cycle. At end expiration PEEP, if adequate will keep open only the lung regions already opened by applied Pplat

Applied physiology of intensive care medicine. Pinsky, Mancebo, pg 307

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

Recruitment and Derecruitment during Acute Respiratory Failure: A Clinical Study S Crotti, D Mascheroni, P PelosiI, J J. Marini, L Gattinoni. Am J Respir Crit Care Med 2001,Vol 164. pp 131140, 2001

recruitment occurs along entire VP curve of respiratory system, even beyond the UIP derecruitment is also a continuous process, but is most prevalent over a pressure range (010cm H2O) lower than the pressure range over which recruitment occur

Venegas JG, Harris RS, Simon BA. A comprehensive equation for the pulmonary pressure-volume curve. J Appl Physiol 1998;84:389395.

Result of confluence of basic and clinical research

ARDSNET TRIALS

BASIC RESEARCH
Experimental pulmonary oedema due to intermittent positive pressure ventilation with high Inflation pressures: protection by positive end expiratory pressure. Webb HH, Tierney DG. Am Rev Respir Dis 1974; 110: 556 Rats were ventilated with varying level of PIP and PEEP PIP 14 cmH2O 30 cmH2O 45 cmH2O 45 cmH2O PEEP 0 0 0 10 No pathological or physiological changes Perivascular odema; no alveolar odema Alveolar and perivascular odema, decreased compliance, hypoxaemia and gross anatomical changes No alveolar odema

BAROTRAUMA

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

BASIC RESEARCH
High inflation pressure pulmonary odema. Respective effects of high airway pressure, high tidal volume and positive end expiratory pressure. Dreyfuss D, Basset G, Soler P, Saumon G. Am Rev Respir dis, 1988; 137:1159

Ventilated rats with high Paw with and without chest wall strapped

Rats with strapped chest Paw - very high VT modest No lung damage

Rats without strapped chest Paw - very high VT very high Dramatic changes in lung

TRANSPULMONARY PRESSURE- VOLUTRAUMA

PEEP effective in preventing damage in large VT rats

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

BASIC RESEARCH

INFERENCE 1. 2. 3. High tidal volume ventilation causes acute lung injury PEEP exerts a protective effect against this injury

High tidal volume ventilation can result in distant organ injury

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

CLINICAL RESEARCH CT SCAN CORRELATED WITH LUNG MECHANICS

INFERENCE 1. 2. 3. Lung is non- homogenous Lung is small not stiff

Compartment of aerated alveoli ( baby lung) is subject to overdistension

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

HYPOTHESIS
End inspiratory lung volume should be limited to avoid alveolar overdistension (volutrauma)

cycles of end expiratory derecruitment following inspiratory recruitment (avoid biotrauma and atelectotrauma)

Sufficient PEEP should be applied to prevent

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

3 multicenter RCTs

Authers

Year published/ enrollment 1998 (1990-1995) 1998 (1994-1996) 1998 (1995-1996)

No. patient s 53 116 120

Mortality Low VT 38%* 45%** 46.5%^ 50%

Mortality High VT 71%* 71%** 37.9%^ 47%

p Value

Amato et al Brochard et al Stewart et al

<0.000 1 0.39 0.72

*mortality at 28 days **mortality at hospital discharge ^mortality at 60 days mortality at hospital discharge

Amato et al, 1998, NEJM

Open lung approach

Conventional ventilation lowest PEEP for acceptable oxygenation VT - 12 ml/ kg actual bw PaCO2:35-38 mm Hg

Protective ventilation PEEP above LIP on static P/V curve VT < 6 ml/ kg actual bw Pplat < 20 cmH2O above PEEP Permissive hypercapnia,

Brochard et al, 1998, AJRCCM Conventional ventilation PEEP 10 cmH2O Pplat 31 cmH2O VT - 10 ml/ kg actual bw PaCO2:53-60 mm Hg Stewart et al, 1998, NEJM Conventional ventilation PEEP 7-8 cmH2O Pplat 26-28 cmH2O VT - 10 ml/ kg actual bw PaCO2:45 mm Hg Protective ventilation PEEP 8 cmH2O Pplat 22 cmH2O VT - 7 ml/ kg actual bw PaCO2:54 mm Hg
Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,

Protective ventilation PEEP 10 cmH2O Ppat 25 cmH2O VT - 7 ml/ kg actual bw PaCO2:41-44 mm Hg

Acute Respiratory Distress Syndrome Clinical Network (ARDSNet)

NIH-funded, NHLBI sponsored, consortium of 10 centers, 24 hospitals, 75 intensive care units Goal to design large RCTs to determine effective treatments Key ARDSnet studies:
Tidal volume- low vs high - 2000 PEEP- low vs high - 2004 Steroids - 2006 Fluid volume management/PA catheter - 2006

Ventilation with lower tidal volume as compared to traditional tidal volume for acute lung injury and the acute respiratory distress syndrome- ARMA STUDY NEJM 2000, 342;18

861 patients

Conventional ventilation PEEP- 5-24 cm H2O Pplat 50 cm H2O VT 10-12 ml/ kg IBW PaCO2- 35 mm Hg

Protective ventilation PEEP- 5-24 cm H2O Pplat 30 cm H2O VT 6-8 ml/ kg IBW PaCO2- 40 mm Hg Permissive hypercapnia and acidosis

22% relative mortality reduction 9% absolute mortality reduction

Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome- ALVEOLI STUDY NEJM, 2004, 351;4

549 patients HIGHER PEEP PEEP- 133 cm H2O Pplat 267 cm H2O VT 5.81 ml/ kg IBW PaO2/FiO2- 20676 Mortality 27% LOWER PEEP PEEP- 83 cm H2O Pplat 246 cm H2O VT 61 ml/ kg IBW PaO2/FiO2 - 16969 Mortality 24.9%%

similar mortality rate despite significant improvement in PaO2/FiO2 Higher PEEP group had higher Pplat despite lower TV ? Benefit of higher PEEP negated by overdistension

Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome NEJM, 2006, 354;16

180 patients >7days of unresolving ARDS methylprednisolone 2mg/kg iv stat followed by 0.5 mg/kg q6h for 14 days then tapering to 0.5 mg/kg q12h for 7 days

no survival benefit If given 2 weeks after onset of ARDS - significantly increased mortality improved cardiopulmonary physiology within 3-7 days after their initiation and altered the course of ARDS increased number of ventilator-free days, ICU-free days, and shockfree days during the first 28 days

Comparison of Two Fluid-Management Strategies in Acute Lung Injury N EJM, 2006;354:2564-75

1000 patients

no significant difference in 60-day mortality conservative strategy improved lung function and shortened the duration of mechanical ventilation and intensive care without increasing non pulmonary-organ failures

Pulmonary-Artery versus Central Venous Catheter to Guide Treatment of Acute Lung Injury NEJM, 2006,354;21

1000 patients

PAC-guided therapy did not improve survival or organ function but associated with more complications than CVC-guided therapy

I would rather discover a single fact, even a small one, than debate the great issues at length without discovering anything at all.
Galileo Galilei

VENTILATOR SCORE Smith and Gordon-1986

age PA-aO2 mean peak airway pressure

Vertical gradient of regional lung inflation in adult respiratory distress syndrome

P Pelosi, L D'Andrea, G Vitale, A Pesenti and L Gattinoni D'Andrea,

Am. J. Respir. Crit. Care Med., Vol 149, No. 1, 01 1994, 8-13. Respir. Crit. 8-

We obtained chest CT sections in 12 normal subjects (controls) and 17 patients with ARDS to investigate regional lung inflation. A basal CT section (just above the diaphragm) was obtained in the supine position at ZEEP. In each CT section the distance from ventral to dorsal surface (hT) was divided into 10 equal intervals, and 10 lung levels from ventral (no. 1) to dorsal (no. 10) were defined. Knowing the average density and the volume of each level, we computed: (1) the tissue volume; (2) the gas/tissue (g/t) ratio (index of regional inflation); (3) the hydrostatic pressure superimposed on each level (SPL), estimated as density x height. The total volume of the basal CT section was 49 +/- 2.5 ml x m-2 (mean +/- SE) in control subjects and 43 +/- 2.3 ml x m-2 in patients with ARDS (p = not significant [NS]). The tissue volume, however, was 16.7 +/- 0.8 ml x m-2 in control subjects and 31.6 +/- 1.7 ml x m-2 in patients with ARDS (p < 0.01). The g/t ratio in level 1 averaged 4.7 +/- 0.5 in control subjects and 1.2 +/- 0.2 in patients with ARDS (p < 0.01), and this ratio decreased exponentially from level 1 to level 10, both in controls and patients with ARDS. The Kd constant of the exponential decrease was 13.9 +/- 1.3 cm in control subjects and 7.8 +/- 0.8 cm in patients with ARDS (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Ubaidur Rahaman, S.R., CCM, SGPGIMS, Lucknow Rahaman,