Evaluating muscle mass in survivors of ARDS:
a 1-year multi-center longitudinal study
Kitty S. Chan, PhD1*, Marina Mourtzakis, PhD2*, Lisa Aronson Friedman, ScM3,4, Victor D. Dinglas, MPH3,4, Catherine L. Hough, MD, MSc5,
E. Wesley Ely, MD, MPH6,7, Peter E. Morris, MD8,
Ramona O. Hopkins, PhD9,10,11, Dale M. Needham, FCPA, MD, PhD3,4,12
with the National Institutes of Health National Heart, Lung, and Blood Institute (NHLBI) Acute Respiratory Distress Syndrome (ARDS) Network
Online Methods Supplement
Investigators and research staff from the National Institutes of Health National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network sites: University of Washington, Harborview (*L. Hudson, S. Gundel, C. Hough, M. Neff, K. Sims, A. Ungar, T. Watkins); Providence-Everett Medical Center (S. Lubatti, T. Ziedalski); Baystate Medical Center (*J. Steingrub, M. Tidswell, E. Braden, L.
DeSouza, C. Kardos, L. Kozikowski, S. Ouellette); Baylor College of Medicine (K.
Guntupalli, V. Bandi, C. Pope, C. Ross); Johns Hopkins University (*R. Brower, H.
Fessler, D. Hager, P. Mendez-Tellez, D. Needham, K. Oakjones); Johns Hopkins Bayview Medical Center (J. Sevransky, A. Workneh); University of Maryland (C.
Shanholtz, D. Herr, H. Howes, G. Netzer, P. Rock, A. Sampaio, J. Titus); Union Memorial Hospital (P. Sloane, T. Beck, D. Highfield, S. King); Washington Hospital Center (B. Lee, N. Bolouri); Franklin Memorial Hospital Center (S. Selinger, S. King); St Josephs Hospital of Baltimore (L. Barr); Cleveland Clinic Foundation (*H.P.
Wiedemann, R.W. Ashton, D.A. Culver, T. Frederick, J.A. Guzman, J.J. Komara Jr, A.J.
Reddy); University Hospitals of Cleveland (R. Hejal, M. Andrews, D. Haney);
MetroHealth Medical Center (A.F. Connors, S. Lasalvia, J.D. Thornton, E.L. Warren);
University of Colorado Hospital, Aurora (*M. Moss, E.L. Burnham, L. Gray, J. Maloney, M. Mealer); Denver Health Medical Center (I. Douglas, K. Overdier, K. Thompson, R.
Wolken); Rose Medical Center (S. Frankel, J. McKeehan); Swedish Medical Center (M.L. Warner); Saint Anthony's Hospital (T. Bost, C. Higgins, K. Hodgin); Duke University (*N. MacIntyre, L. Brown, C. Cox, M. Gentile, J. Govert, N. Knudsen);
University of North Carolina (S. Carson, L. Chang, S. Choudhury, W. Hall, J. Lanier);
Vanderbilt University (*A.P. Wheeler, G.R. Bernard, M. Hays, S. Mogan, T.W. Rice);
Wake Forest University (*R.D. Hite, A. Harvey, P.E. Morris, Mary Ragusky); Moses Cone Memorial Hospital (P. Wright, S. Groce, J. McLean, A. Overton); University of Virginia (J. Truwit, K. Enfield, M. Marshall); Intermountain Medical Center (*A. Morris,
*C. Grissom, A. Austin, S. Barney, S. Brown, J. Ferguson, H. Gallo, T. Graydon, E.
Hirshberg, A. Jephson, N. Kumar, M. Lanspa, R. Miller, D. Murphy, J. Orme, A. Stowe, L. Struck, F. Thomas, D. Ward); LDS Hospital (P. Bailey, W. Beninati, L. Bezdjian, T.
Clemmer, S. Rimkus, R. Tanaka, L. Weaver); McKay Dee Hospital (C. Lawton, D.
Hanselman); Utah Valley Regional Medical Center (K. Sundar, W. Alward, C. Bishop, D.
Eckley, D. Harris, T. Hill, B. Jensen, K. Ludwig, D. Nielsen, M. Pearce); University of California, San Francisco (*M.A. Matthay, C. Calfee, B. Daniel, M. Eisner, O. Garcia, K.
Kordesch, K. Liu, N. Shum, H. Zhou); University of California, San Francisco, Fresno (M.W. Peterson, J. Blaauw, K. Van Gundy); San Francisco General Hospital (R. Kallet, E. Johnson); University of California, Davis (T. Albertson, B. Morrissey, E. Vlastelin);
Stanford (J. Levitt, E. Kovoor, R. Vojnik); Louisiana State University Health Sciences Center-New Orleans (*B. deBoisblanc, A. Antoine, D. Charbonnet, J. Hunt, P. Lauto, A.
Marr, G. Meyaski, C. Romaine); Earl K. Long Medical Center (S. Brierre, J. Byrne, T.
Jagneaux, C. LeBlanc, K. Moreau, C. Thomas); Ochsner Clinic Foundation (S. Jain, D.
Taylor, L. Seoane); Our Lady of the Lake Medical Center (C. Hebert, J. Thompson);
Tulane Medical Center (F. Simeone, J. Fearon). Clinical Coordinating Center:
Massachusetts General Hospital and Harvard Medical School (*D. Schoenfeld, N.
Dong, M. Guha, E. Hammond, P. Lazar, R. Morse, C. Oldmixon, N. Ringwood, E.
Smoot, B.T. Thompson, R. Wilson). National Heart, Lung, and Blood Institute: A.
Harabin, S. Bredow, M. Waclawiw, G. Weinmann. Data and Safety Monitoring Board: R.
G. Spragg (chair), A. Slutsky, M. Levy, B. Markovitz, E. Petkova, C. Weijer. Protocol Review Committee: J. Sznajder (chair), M. Begg, L. Gilbert-McClain, E. Israel, J. Lewis, S. McClave, P. Parsons. *Principal investigator.
I. Inclusion/Exclusion Criteria for Parent ARDSNet Clinical Trials of DXA Study Participants
Trial Inclusion Criteria Exclusion Criteria
(Most commonly used) ALTA Patients with ALI
Intubated and receiving mechanical ventilation
A ratio of PaO2 to FIO2 (fraction of inspired oxygen) ≤ 300 (adjusted for altitude as appropriate)
Bilateral pulmonary infiltrates consistent with edema on frontal chest radiograph
No clinical evidence of left atrial hypertension.
ALI >48 h
Chronic lung disease
Acute MI
High 6 month mortality
Chronic liver disease
Neuromuscular disease
Unable to obtain consent
Physician refusal
Not committed to full support
OMEGA Patients with ALI
mechanical ventilation
Physicians intend to administer enteral nutrition
A ratio of PaO2 to FIO2 ≤ 300 (adjusted if altitude exceeded 1000 m)
Bilateral pulmonary infiltrates consistent with edema on chest radiograph
No clinical evidence of left atrial hypertension
ALI >48 h or >72 h mechanical ventilation
Severe chronic lung disease
Likely fatal underlying disease
Recent intracranial hemorrhage
Severe liver disease
Refractory shock
Coagulopathy
Moribund
Inability to obtain consent
Refused consent EDEN Patients with ALI
mechanical ventilation
Physician intend to administer enteral nutrition
A ratio of PaO2 to FIO2 ≤ 300 (adjusted if altitude exceeded 1000 m)
Bilateral pulmonary infiltrates consistent with edema on chest radiograph
No clinical evidence of left atrial hypertension
ALI >48 h or >72 h mechanical ventilation
Chronic lung disease
Fatal underlying disease
Severe liver disease
Refractory shock
Intracranial hemorrhage
Total parenteral nutrition
Severe neuromuscular disease
Severe malnutrition
Moribund
Unable to provide consent
Physician refusal
Refused consent
Not committed to full support
SAILS Patients with ALI from sepsis:
Positive-pressure mechanical ventilation through an endotracheal tube
A ratio of PaO2 to FIO2 ≤ 300 (adjusted if altitude exceeded 1000 m)
Bilateral infiltrates on chest radiography consistent with pulmonary edema
No evidence of left atrial hypertension.
Additional criteria:
A known or suspected infection
Systemic inflammatory response, defined as at least 1 of following 3 criteria; one criteria must be either WBC or body temperature criteria:
o white-cell count >12,000 or <4000 or differential count with >10%
band forms
o body temperature of >38°C or
<36°C
o heart rate (>90 beats/min) or receiving medications that slow heart rate or paced rhythm
ALI >48 h
>7 days mechanical ventilation time window
Had CK, ALT, or AST level
>5x ULN
Severe chronic liver disease
Chronic respiratory failure
Interstitial lung disease
Moribund
Received statin in previous 48 hr
Physician insist on statin use
Unable to absorb study drug
Did not have central venous access
Withdrawn by physician
Were unable to provide consent
Declined to provide consent
Not committed to continuing ICU procedures
DXA-related exclusions:
We also had exclusions related to DXA measurement for the 6- and 12-m follow-up, including:
height/weight outside of machine limits
being pregnant
non-consent for DXA References
National Heart Lung Blood Institute ARDS Clinical Trials Network. Randomized Placebo- controlled Clinical Trial of an Aerosolized b2-Agonist for Treatment of Acute Lung Injury. Am J Respir Crit Care Med 2011;184:561–568. (ALTA)
Rice TW, Wheeler AP, Thompson BT, deBoisblanc BP, Steingrub J, Rock P, for the NHLBI ARDS Clinical Trials Network. Enteral Omega-3 Fatty Acid gamma-Linolenic Acid and
Antioxidant Supplementation in Acute Lung Injury. JAMA 2011;306(14):1574-1581. (OMEGA) National Heart Lung Blood Institute ARDS Clinical Trials Network. Initial tropic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial JAMA 2012;307(8):795- 803. (EDEN)
National Heart Lung Blood Institute ARDS Clinical Trials Network. Rosuvastatin for Sepsis- Associated
Acute Respiratory Distress Syndrome. N Engl J Med 2014;370:2191-2200 (SAILS)
II. Study Flowchart
III. Missing Data on Baseline, Hospital and Physical Outcomes
Variable Group Missing Level
0%
(N variables)
<5%
(N variables)
≥ 5%
(N variables) 6m DXA analyses
Baseline characteristics (N=10) 8 1 1 (43.8%)*
Hospital/ICU exposures (N=16) 14 1 1 (7.9%)
Physical outcomes (16) 3 13 0
12m DXA analyses
Baseline characteristics (N=10) 8 1 1 (40.0%)*
Hospital/ICU exposures (N=16) 14 1 1 (5.9%)
Physical outcomes (16) 7 9 0
*Rheumatologic comorbid data not collected in one trial (SAILS)
IV. Step by Step Process to Standardize DXA Output for ALTOS Study Centers (1 machine per center)
(see reference list at end of document for sources used in creating this document) Step 1: Determine which machine was used based on data below:
Study Center Machine Software Version & Dates Calibration Method
Center A Hologic N/A NHANES Pre-Apex 3.4
Center B (8 sites) Hologic Software version 12.6:5. Classic
Center C Hologic 4/14/10: Discovery 3.01
8/13/10: Discovery 3.1.1APEX
3/10/11: Physician Viewer 6.2 9/13/11: Discovery 3.3 Apex
NHANES Pre-Apex 3.4
Center D (4 sites) Hologic GE software, Version 11.4 NHANES Pre-Apex 3.4
Center E GE IDXA N/A
Step 2: Standardize the Hologic values among sites Hologic devices
The older software (V 12.6) underestimates fat mass and overestimates lean tissue mass.
Therefore, in the newer software versions (QDR and Apex) there is a feature called “NHANES BCA”. When NHANES BCA is turned on, % fat is calculated 3-4% higher than it would be calculated in Classic mode. Hence, “Classic” calculations must be converted to “NHANES Pre- Apex 3.4.” calculations.
Step A: Convert each of the Classic Fat Masses (Center B) to NHANES Pre-Apex 3.4 Fat Masses using the following equation:
FATMassNHANES_PreAPEX3.4= FATClassic+ 0.054*(LeanSoftTissueMassClassic + BMCClassic) Step B: Convert each of the Lean Tissues Masses to NHANES Pre-Apex 3.4 Lean Tissue Masses using the following equation:
LeanSoftTissueMassNHANES_PreAPEX3.4= Total MassClassic – BMCClassic - FATMASSNHANES_PreAPEX3.4 (From A bove)
Step C: Calculate a new Lean+BMC Value using the following equation:
Lean+BMCNHANES_PreAPEX3.4= LeanSoftTissueMassNHANES_PreAPEX3.4 + BMCClassic
Step D: Convert each of the new NHANES Pre-Apex 3.4 Fat Values to % Fat using the following equation:
% FatNHANES_PreAPEX3.4 = (FatNHANES_PreAPEX3.4)/(Total MassNHANES_PreAPEX3.4)
Step 3: For Center E, since GE IDEXA DXA machine was used, only the following DXA measurements can be converted and merged with the rest of the ALTOS centers DXA datasets
1. Total bone mineral content (BMC) 2. Subtotal BMC (trunk + all 4 limbs) 3. Total percent fat
4. Appendicular lean soft tissue mass (lean mass of 4 limbs) 5. Trunk percent fat
6. Leg percent fat
Convert GE IDexa to Hologic Values for the following measures 1. Total bone mineral content (BMC)
For patients weight≤40kg.
Total BMCHologic= 134.166 + 1.035*Total BMCGE– 0.010*Total Lean MassGE – 0.009*Total FatGE
For patients weight>40kg.
Total BMCHologic= 3.741 + 1.085 Total BMCGE – 0.009Total Lean MassGE + 0.001Total FatGE
2. Subtotal BMC (trunk + all 4 limbs) For patients weight≤40kg.
Subtotal BMCHologic= 164.144 + 1.038*Subtotal BMCGE– 0.009*Total Lean MassGE – 0.008*Total FatGE
For patients weight>40kg.
Subtotal BMCHologic= 13.428 + 1.016*Subtotal BMCGE – 0.006 *Total Lean MassGE + 0.001*Total FatGE
3. Total percent fat
Total Percent FatHologic = 1.943 + 0.894*Total Percent FatGE
4. Appendicular lean soft tissue mass (ALSTM) (lean mass of 4 limbs) ALSTMHologic = 818.24 + 0.989*ALSTNMGE
5. Trunk percent fat
Trunk Percent FatHologic = 2.623 + 0.801*Trunk Percent FatGE
6. Leg percent fat (both legs)
Legs Percent FatHologic = -1.576 + 1.063* Legs Percent FatGE
Hologic. (2013) Hologic Advanced Body Composition Analysis and NHANES Calibration.
Bedford, MA
Shepherd J, Fan B, Lu Y, Xiao W, Wacker W, Ergun D, Levine, M. (2012) A Multinational Study to Develop Universal Standardization of Whole-Body Bone Density and Composition Using GE Healthcare Lunar and Hologic Systems. Journal of Bone and Mineral Research, 27(10), 2208-2216.
