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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
2
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
3
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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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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sFigure 4 – Odds ratio for hospital mortality of increasing MFI values versus MFI = 0 according to
increasing SOFA scores (y axis in log scale).
17
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)