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Electronic Supplementary Material (ESM)

Association of frailty with short-term outcomes, organ support and resource use in

critically ill patients

Zampieri FG et al., for the ORCHESTRA Study Investigators

The ORCHESTRA (ORganizational CHaractEeriSTics in cRitcal cAre) Study

Steering Committee: Marcio Soares (PI), Jorge I. F. Salluh, Fernando A. Bozza (Instituto D’Or de Pesquisa

e Ensino, Rio de Janeiro); Derek C. Angus, Jeremy M. Kahn (CHRISMA, University of Pittsburgh Medical

Center, Pittsburgh); Luciano C. P. Azevedo (Hospital Sírio Libanês, São Paulo); Fernando G. Zampieri

(Hospital do Coração - HCor, São Paulo); Thiago Lisboa (Santa Casa de Misericórdia de Porto Alegre,

Porto Alegre); Thiago D. Corrêa (Hospital Israelita Albert Einstein, São Paulo); Bruno F. Mazza (Hospital

Samaritano, São Paulo); William N. Viana (Hospital Copa D’Or, Rio de Janeiro); Theodore J. Iwashyna

(Department of Internal Medicine, University of Michigan; Veterans Affairs Center for Clinical

Management Research, Ann Arbor).

Data Management and Secretariat: Grazielle V. Ramos, Aline R. Silva (Instituto D’Or de Pesquisa e

Ensino, Rio de Janeiro).

Statistical analyses: Fernando G. Zampieri (Hospital do Coração- HCor, São Paulo); Lunna P. Borges

(Epimed Solutions, Rio de Janeiro).

Investigators and Participating Centers

Bahia: Hospital Agenor Paiva, Salvador (UTI: Maristela Medeiros Machado); Hospital Santa Helena,

Camaçari (UTI Geral: Luciano Ferreira de Souza, Maristela Medeiros Machado); Distrito Federal:

Hospital Anchieta Distrito Federal, Taguatinga (UTI A: Rubens Antônio Bento Ribeiro, Eduardo Cesar

Guimarães Lessa); Hospital Brasília, Brasília (UTIs 1 and 2: Clayton Barbieri de Carvalho, Tullio Xavier

Leirias); Hospital Santa Luzia Rede D'Or São Luiz DF, Brasília (UTIs 1, 2, T and C: Marcelo de Oliveira

Maia, Edmilson Leal Bastos, Rebeca Martins da Silva Barros, Cintya M.V. Oliveira, Jose Aires A Neto);

Espírito Santo: Hospital Unimed Vitória, Vitória (UTI Adulto Geral: Eliana Bernadete Caser, Silvane

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Damasceno); Goiás: Hospital Geral de Goiânia, Goiânia (UTIs Alas A, B and C: Marcelo Rabahi Fouad,

Marco Antônio Mendes Castilho; Durval Ferreira Fonseca Pedroso; Humberto Borges Barbosa);

Maranhão: Hospital de Câncer do Maranhão Tarquínio Lopes Filho, São Luís (UTI Geral: Ana Paula

Pierre de Moraes); UDI Hospital, São Luís (UTI: Ana Cláudia Pinho de Carvalho, Alexandre Guilherme

Ribeiro de Carvalho, Akemy Carvalho do Rosário); Minas Gerais: Santa Casa de Caridade de Diamantina,

Diamantina (UTI Dr Jose Aristeu de Andrade: Marcelo Ferreira Sousa, Marcia Maria Ferreira de Souza);

Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte (UTI PS: Saulo Fernandes

Saturnino); Paraíba: Hospital Universitário Lauro Wanderley, João Pessoa (UTI Adulto: Ciro Leite

Mendes, Paulo César Gottardo, Igor Mendonça do Nascimento); Pernambuco: Hospital Esperança, Recife

(UTI Geral: Mariza da Fonte Andrade Lima, Marçal Paiva); Hospital Esperança Olinda, Olinda (UTIs 1, 2,

3 and 4: Carlos Eduardo Ferraz Freitas, Lanecley Gouveia Neves Fulco); Hospital São Marcos, Recife (UTI

Geral: Maurício Magalhães Cabral, Luciane Ishiy, Renato Fábio Alberto Della Santa Neto); Rio de Janeiro:

Hospital Estadual Getúlio Vargas, Rio de Janeiro (Giulliana Martines Moralez; UTI 1: Giulliana Martines

Moralez, Flavio Callil; UTI 2: Claudio Eduardo Calife Chagas, Eliane Casanova; UPO: Antonio Carlos

Babo Rodrigues, Bruno Vidal); Clínica São Vicente, Rio de Janeiro (CTI 1: Arthur O. A. Vianna, Patrícia

Soares D'Alessandro); Hospital Estadual Adão Pereira Nunes, Duque de Caxias (UTI Geral and UPO:

Robson Correa Santos, Ricardo Pessoa Martelo); Hospital Estadual Carlos Chagas, Rio de Janeiro (UTI

Geral: Rodrigo Barros, Luisa Chuairi); Hospital Quinta D'Or, Rio de Janeiro (Roberto Costa; UTI A:

Cristiane Belo, Giulia P. C. Lima; UTI C: Cristiane Cariús, Eduardo Xavier; UCV-1: Claudia Lourenço de

Almeida, Rafael Sibanto; UHB: Alessandra Longo, Joyce Roma; UHO: Juliana Gurgel da Silveira, Laura

Brasil Herranz; UNI: Gustavo Vaz, Bruno Cartelo Branco; UPO: Leonardo Campioni, Alexandre Coscia);

Hospital Barra D'Or, Rio de Janeiro (UPO: Walter Homena; CTI 1, CTI 2 and UTI Neurointensiva: Marcelo

de Sousa Santino, Juan Carlos Verdeal); Hospital Copa D'Or, Rio de Janeiro (William Nascimento Viana

e Lígia Sarmet Farah Cunha Rabello; UTI Neurointensiva: Janaína Oliveira; UTIs Amarela and Azul:

Cecília Magno; UTI Lilás: Alex Gaspar; UTI Verde: Guilherme Feres; UPO: Maria Teresa Saint-Martin);

Hospital Caxias D'Or, Duque de Caxias (UTI Sarapuí: Eric Perecmanis); Hospital Norte D'Or, Rio de

Janeiro (UTI Geral: Jorge Eduardo da Silva Soares Pinto, Sergio Teixeira Sant'Anna Junior); Hospital Oeste

D'Or, Rio de Janeiro (UTI 2º ANDAR: Guilherme Brenande Alves Faria, Alcino Márcio Toledo de

Medeiros; UTI 5º ANDAR: Márcia Adélia de Magalhães Menezes, Rosa Imaculada Stancato; Joyce

Andrade); Hospital Rios D'Or, Rio de Janeiro (UTI 1: Alessandra Alves); Hospital Badim, Rio de Janeiro

(CTIs A and B: Alexandre Vaz Scotti); Hospital Municipal Souza Aguiar, Rio de Janeiro (CTIs ADULTO

1 and 2: Roberto Seabra Lannes, Sion Divan Filho, Andrea Ludovico); Hospital São Lucas, Rio de Janeiro

(Marcos Knibel; UTI 1º Andar: Emir Oliveira; UTI 2º Andar: Pedro Azambuja; UTI 4º Andar: Aline

Affonso); Hospital Unimed Costa do Sol, Campos dos Goytacazes (UTIs Adulto I and II: Joel Tavares

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Passos); Hospital Niterói D'Or, Niterói (UTI Geral: Carlos Cesar Hortala Junior); Hospital Israelita Albert

Sabin, Rio de Janeiro (UTI: Edmundo de Oliveira Tommasi, Patricia Frascari Litrento, Alexandra

Gonçalves da Silva); SAMER Hospital, Resende (UTI 1: Henrique Miller Balieiro, Fellipe de Freitas

Pereira); Hospital Estadual Alberto Torres, São Gonçalo (Ulisses de Oliveira Melo; UTI Trauma: Edson

Tristão, Kelsey Sampaio, Rogerio Silveira; UTI Adulto: Antonio Carlos, Felipe Mafort, Jose Hipólito,

Valquíria Queiroz); Instituto Nacional de Câncer - HC II, Rio de Janeiro (CTI: Bruno Azevedo da Cruz,

Karla Biancha Silva de Andrade); Rio Grande do Sul: Hospital Santa Rita, Santa Casa de Misericórdia de

Porto Alegre, Porto Alegre (UTI: Thiago Lisboa, André P. Torelly); Pavilhão Pereira Filho, Santa Casa de

Misericórdia de Porto Alegre, Porto Alegre (UTI: Daniella Birriel); Hospital Dom Vicente Scherer, Santa

Casa de Misericórdia de Porto Alegre, Porto Alegre(UTI de Transplantes: Edison Moraes Rodrigues Filho);

Hospital Montenegro, Montenegro (UTI: José Pettine, Moreno Calcagnotto dos Santos, Tiago Almeida

Ramos, Fernando Bourscheit, Ana Flávia Gallas Leivas); São Paulo: Hospital São Francisco, Ribeirão

Preto (UTI Geral: Marcus Antonio Ferez, Edson Antonio Nicolini); Hospital Vivalle, São José dos Campos

(UTI Geral: Fernando Vinicius Cesar De Marco, Guilherme Paro de Toledo); Fundação Pio XII - Hospital

de Câncer de Barretos, Barretos (UTI: Ulysses V. Andrade e Silva, Cristina Prata Amendola); Hospital

Alemão Oswaldo Cruz, São Paulo (UTI Adulto: Fernando Colombari); Hospital Israelita Albert Einstein,

São Paulo (UTI Adulto: Thiago Domingos Corrêa, Eliézer Silva); Hospital Sírio-Libanês, São Paulo (UTI

Geral: José Mauro Vieira Jr, Luciano Azevedo, Fernando Ramos); Hospital São Luiz - Unidade Assunção,

São Bernardo do Campo (UTI: Silvia Regina Ramos, Lilian Mara Perroud Miilher); Hospital Sepaco, São

Paulo (UTI Adulto: Flávio Geraldo Rezende de Freitas, Antônio Tonete Bafi, Eduardo Souza Pacheco);

Hospital Santa Paula, São Paulo (UTIs A, B and Neuro: Dieter Eduardo Siefeld Araya, Ronaldo Escudeiro

Borba, Moacyr Fogolin Junior, Pedro Ivo Buainain, Mariza Luciana Pregun); Hospital do Rim, São Paulo

(UTI: Flávio Geraldo Rezende de Freitas, Antônio Tonete Bafi); Rede Dor São Luiz – Unidade Morumbi,

São Paulo (UTI 2º Andar: José Albani Carvalho Jr); Rede Dor São Luiz – Unidade Itaim, São Paulo (UTI:

José Albani Carvalho Jr, Mariza Silva Ramos Loesch, Kassia Pinho); Hospital Samaritano, São Paulo

(Bruno Franco Mazza; UTIs Oeste e Neuro: Samantha Longhi de Almeida; UTI Geral: Rosa Goldstein

Alheira Rocha); Hospital do Coração – HCor, São Paulo (UTI Geral: Edson Romano, Fernando Zampieri);

Hospital Nove de Julho, São Paulo (UTIs 2C, 3C, 4D and D: Carlos Eduardo Nassif Moreira); Hospital da

Luz - Vila Mariana, São Paulo (UTI Adulto: Bruno Adler Maccagnan Pinheiro Besen, Carlos Eduardo

Brandão)

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Box 1 – Modified Frailty Index

Variable, 1 point for each

History of diabetes mellitus

Functional status 2 (not independent)

History of COPD or pneumonia*

History of congestive heart failure

History of myocardial infarction

History of percutaneous coronary intervention, angina or stenting

History of hypertension requiring medication

History of peripheral vascular disease or ischemic rest pain

History of impaired sensorium

History of transient ischemic attack or cerebrovascular accident

History of cerebrovascular accident with neurologic deficit

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Box 2 – Frequency of each Modified Frailty Index criteria in the sample

Variable Number of patients (%)

History of diabetes mellitus 30823 (23.8)

Functional status 2 (not independent) 36384 (28.1)

History of COPD or pneumonia* 7542 (5.8)

History of congestive heart failure 7289 (5.6)

History of myocardial infarction 7772 (6.0)

History of percutaneous coronary

intervention, angina or stenting 1799 (1.4)

History of hypertension requiring

medication 67241 (51.9)

History of peripheral vascular disease

or ischemic rest pain 2340 (1.8)

History of impaired sensorium 7913 (6.1)

History of transient ischemic attack or

cerebrovascular accident 3793 (2.9)

History of cerebrovascular accident

with neurologic deficit 5067 (3.9)

MFI is calculated as the simple sum of all present variables. The only variable unavailable in the database

was the presence/absence of previous pneumonia (ref: Farhat JS, Velanovich V, Falvo AJ, Horst HM,

Swartz A, Patton JH Jr, Rubinfeld IS. Are the frail destined to fail? Frailty index as predictor of surgical

morbidity and mortality in the elderly. J Trauma Acute Care Surg 2012; 72:1526-1530)

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Supplementary Tables

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sTable 1 – Characteristics and Outcomes of included patients stratified according to MFI

Modified Frailty Index

0 1 2 3 4 >5 p

Number of patients 40,779 36,175 28,232 15,475 6,606 2,413

Age (years) (mean (sd)) 48·55

(19·07) 61·97

(17·92) 69·81

(14·89) 74·71

(12·94) 77·10

(11·83) 77·95

(11·00) <0·001

SOFA Score (points) (mean (sd)) 2·72

(3·53) 3·04

(3·55) 3·37

(3·61) 3·87

(3·74) 4·26

(3·84) 4·60

(3·85) <0·001

SAPS 3 (points) (mean (sd)) 39·76

(15·06) 44·45

(15·76) 47·80

(15·41) 51·84

(15·62) 54·78

(15·27) 56·53

(15·67) <0·001

Admission type, n (%) <0·001

Elective surgery 11,766

(28·9) 10,506

(29·0) 6714

(23·8) 2517

(16·3) 676

(10·2) 199

(8·2)

Medical 25,055

(61·4) 23,236

(64·2) 19,913

(70·5) 12,150

(78·5) 5590

(84·6) 2090

(86·6)

Urgent surgery 3958 (9·7)

2433 (6·7)

1605 (5·7)

808 (5·2)

340 (5·1)

124 (5·1)

LOS before ICU (days) (median

[IQR]) 0

[0 1] 0

[0 1] 0

[0-1] 0

[0-1] 0

[0-2] 0

[0-3] <0·001

Comorbidities

CCI (points) (mean (sd)) 0·80 (1·65) 1·14 (1·76) 1·73 (1·72) 2·39 (1·76) 3·17 (1·80) 4·28 (2·17) <0·001

Performance status impairment,

n (%) <0·001

Absent / minor 40,779

(100·0) 28,256

(78·1) 17,573

(62·2) 5292

(34·2) 1164

(17·6) 232

(9·6)

Moderate 0

(0·0) 5825

(16·1) 7758

(27·5) 7233

(46·7) 3534

(53·5) 1395

(57·8)

Severe 0

(0·0) 2094 (5·8)

2901

(10·3) 2950

(19·1) 1908

(28·9) 786

(32·6)

Solid locoregional tumor 5505

(13·5) 5386

(14·9) 3763

(13·3) 1844

(11·9) 636

(9·6) 253

(10·5) <0·001

Solid metastatic tumor 1970 (4·8)

2096 (5·8)

1310 (4·6)

565 (3·7)

182 (2·8)

58 (2·4)

<0·001

Hematological malignancy 916

(2·2) 709

(2·0) 470

(1·7) 279

(1·8) 71

(1·1) 28

(1·2) <0·001

Cirrhosis Child A-B 391

(1·0) 473

(1·3) 303

(1·1) 121

(0·8) 40

(0·6) 10

(0·4) <0·001

Cirrhosis Child C 379

(0·9) 370

(1·0) 257

(0·9) 90

(0·6) 23

(0·3) 13

(0·5) <0·001

COPD 0

(0·0) 1052 (2·9)

2094 (7·4)

2151

(13·9) 1387

(21·0) 858

(35·6) <0·001

Heart failure NYHA classes II-

III 0

(0·0) 489

(1·4) 1312 (4·6)

1813

(11·7) 1345

(20·4) 835

(34·6) <0·001

Heart failure NYHA class IV 0

(0·0) 120

(0·3) 334

(1·2) 426

(2·8) 358

(5·4) 257

(10·7) <0·001

Diabetes, uncomplicated 0

(0·0) 2517 (7·0)

9604

(34·0) 5976

(38·6) 2893

(43·8) 1092

(45·3) <0·001

Diabetes, complicated 0

(0·0) 833

(2·3) 2685 (9·5)

2706

(17·5) 1753

(26·5) 877

(36·3) <0·001

Outcomes

ICU length of stay (days)

(median [IQR]) 2

[1-4] 2

[1-5] 3

[1-6] 3

[2-7] 4

[2-8] 4

[2-9] <0·001

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Hospital length of stay (days)

(median [IQR]) 7

[4-14] 8

[4-16] 9

[5-19] 11

[6-24] 14

[7-32] 17

[8- 39] <0·001

Hospital mortality, n (%) 5095

(12·5) 5914

(16·3) 5505

(19·5) 4054

(26·2) 2108

(31·9) 887

(36·8) <0·001

Destination at discharge, n (%) <0·001

Home without nursing

support 34,263

(96) 28,917

(96) 21,594

(95) 10,726

(94) 4,165 (93)

1,383 (91)

Other 1,421

(4) 1,344

(4) 1,133

(5) 695 (6)

333 (7)

143 (9)

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sTable 2 – Use of support according to MFI

Modified Frailty Index

0 1 2 3 4 >5 p

Organ Support at Admission

Vasopressors, n (%) 4082

(10·0)

3775

(10·4)

3175

(11·2)

2071

(13·4)

986

(14·9)

409

(16·9) <0·001

Mechanical ventilation, n (%) 6221

(15·3)

5142

(14·2)

4092

(14·5)

2679

(17·3)

1208

(18·3)

494

(20·5) <0·001

Non-invasive

Ventilation , n (%)

1694

(4·2)

1989

(5·5)

1977

(7·0)

1434

(9·3)

797

(12·1)

420

(17·4) <0·001

Renal replacement

Therapy , n (%)

294

(0·7)

470

(1·3)

553

(2·0)

405

(2·6)

190

(2·9)

73

(3·0) <0·001

Organ support at 24 hours

Vasopressors , n (%) 5249

(12·9)

5070

(14·0)

4272

(15·1)

2740

(17·7)

1310

(19·8)

537

(22·3) <0·001

Mechanical ventilation, n (%) 6845

(16·8)

5902

(16·3)

4738

(16·8)

3091

(20·0)

1438

(21·8)

594

(24·6) <0·001

Non-invasive

ventilation, n (%)

2129

(5·2)

2470

(6·8)

2554

(9·0)

1870

(12·1)

1026

(15·5)

535

(22·2) <0·001

Renal replacement

therapy, n (%)

753

(1·8)

1185

(3·3)

1192

(4·2)

773

(5·0)

346

(5·2)

145

(6·0) <0·001

Organ Support During ICU stay

Vasopressors, n (%) 5508

(13·5)

5654

(15·6)

4936

(17·5)

3186

(20·6)

1561

(23·6)

622

(25·8) <0·001

Mechanical ventilation, n (%) 8227

(20·2)

7520

(20·8)

6246

(22·1)

4121

(26·6)

1904

(28·8)

790

(32·7) <0·001

Length of MV, days

(median , [IQR])

4

[2-11]

5

[2-11]

5

[2-12]

6

[2-13]

6

[3-15]

7

[2-14] <0·001

Non-invasive

ventilation, n (%)

3182

(7·8)

3584

(9·9)

3601

(12·8)

2565

(16·6)

1406

(21·3)

723

(30·0) <0·001

Renal replacement

therapy, n (%)

1473

(3·6)

2132

(5·9)

2189

(7·8)

1363

(8·8)

692

(10·5)

280

(11·6) <0·001

Transfusional Support during ICU Stay

Reb blood cells, n (%) 3756

(9·2)

3478

(9·6)

2840

(10·1)

1717

(11·1)

838

(12·7)

345

(14·3) <0·001

Fresh frozen plasma, n (%) 857

(2·1)

745

(2·1)

564

(2·0)

317

(2·0)

169

(2·6)

63

(2·6) 0·038

Platelets, n (%) 789

(1·9)

673

(1·9)

535

(1·9)

292

(1·9)

149

(2·3)

58

(2·4) 0·166

Any transfusion, n (%) 4093

(10·0)

3810

(10·5)

3122

(11·1)

1878

(12·1)

924

(14·0)

368

(15·3) <0·001

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sTable 3 – Results for multivariate regression for mortality

OR Lower Upper

Age 1·029 1·028 1·030

Frailty

Not frail ref ref ref

Pre-frail 1·015 0·832 1·237

Frail 2·415 1·894 3·078

SOFA score (each point) 1·347 1·311 1·384

Admission type

Elective surgery ref ref ref

Medical 3·700 3·109 4·402

Urgent surgery 2·569 2·003 3·295

sTable 4 – Results for multivariate regression for discharge not for home without support

OR Lower Upper Age 0·995 0·997 0·999 Frailty

Not frail ref ref ref Pre-frail 0·534 0·704 0·929 Frail 0·363 0·538 0·795 SOFA score (each point) 0·901 0·959 1·020 Admission type

Elective surgery ref ref ref Medical 0·244 0·310 0·393 Urgent surgery 0·277 0·375 0·508

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sTable 5 – Results for Cox regression for ICU and hospital discharge

HR Lower Upper ICU Discharge

Age 0·995 0·994 0·995

Frailty

Not frail ref ref ref

Pre-frail 0·999 0·986 1·012

Frail 0·942 0·925 0·959

SOFA score (each point) 0·833 0·847 0·850

Admission type

Elective surgery ref ref ref

Medical 0·546 0·539 0·553

Urgent surgery 0·607 0·582 0·612

Hospital Discharge Age 0·991 0·990 0·991

Frailty

Not frail ref ref ref

Pre-frail 0·987 0·972 1·002

Frail 0·792 0·776 0·809

SOFA score (each point) 0·833 0·831 0·835

Admission type

Elective surgery ref ref ref

Medical 0·663 0·654 0·673

Urgent surgery 0·596 0·581 0·611

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Supplementary Figures

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sFigure 1. Study flowchart.

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sFigure 2 – Distribution of MFI in the whole sample

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sFigure 3 – Predicted probability for death according to admission type (age fixed at 40 years)

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sFigure 4 – Odds ratio for hospital mortality of increasing MFI values versus MFI = 0 according to

increasing SOFA scores (y axis in log scale).

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sFigure 5: Probability of being discharged home without nursing care for medically admitted patients

according to frailty status [non-frail (gray), pre-frail (orange) and frail (dark blue)]. Gray areas represent

95% confidence intervals.

18

sFigure 6 – Predicted probability for discharge home without support adjusted for SOFA, with fixed age

of 40 years and stratified according to admission type.

19

sFigure 7 – LOS according to MFI value stratified according to hospital discharge status (alive versus

dead)

20

sFigure 8 – Odds ratio of receiving support with increasing MFI values (y axis in log scale)