A systematic review of biomarkers multivariately associated with acute respiratory distress syndrome development and mortality

van der Zee, Philip; Rietdijk, Wim; Somhorst, Peter; Endeman, Henrik; Gommers, Diederik

doi:10.1186/s13054-020-02913-7

Critical Care

Table 2 Study characteristics for ARDS mortality

From: A systematic review of biomarkers multivariately associated with acute respiratory distress syndrome development and mortality

Study	Study design	Setting	ARDS definition	Outcome	Total (n)	Non-survivors (n)	Age	Gender, male n (%)	Variables in multivariate analysis	Sample moment
Adamzik 2013 [58]	Prospective cohort	Single centre	AECC	30 days	47	17	44 ± 13	32 (68. 1%)	SAPS II score, gender, lung injury score, ECMO, CVVHD, BMI, CRP, procalcitonin	Within 24 h following ICU admission
Ahasic 2012 [24]	Prospective cohort	Multicentre	AECC	60 days	175	78	60.7 ± 17.6	102 (58.3%)	Gender, BMI, cirrhosis, Diabetes, need for red cell transfusion, sepsis, septic shock, trauma	Within 48 h following ICU admission
Amat 2000 [26]	Prospective cohort	Two centre	AECC ARDS	1 month after ICU discharge	21	11	54 ± 16	15 (71.4%)	Not specified	Day 0 ICU
Bajwa 2008 [59]	Prospective cohort	Single centre	AECC	60 day	177	70	68.3 ± 15.3	99 (55.9%)	APACHE III score	Within 48 h following ARDS onset
Bajwa 2009 [60]	Prospective cohort	Single centre	AECC	60 days	177	70	62.5 (IQR 29.0)	100 (56.5%)	APACHE III score	Within 48 h following ARDS onset
Bajwa 2013 [61]	RCT (FACTT)	Multicentre	AECC	60 days	826	NR	48 (38–59 IQR)	442 (53.5%)	APACHE III score	Days 0 and 3
Calfee 2008 [62]	RCT (ARMA)	Multicentre	AECC	180 days	676	NR	51 ± 17	282 (41.7%)	Age, gender, APACHE III score, sepsis, or trauma	Day 0
Calfee 2009 [63]	RCT (ARMA)	Multicentre	AECC	Hospital	778	272	51 ± 17	459 (59.0%)	Age, PaO₂/FiO₂, APACHE III score, sepsis or trauma	Day 0
Calfee 2011 [64]	RCT (ARMA)	Multicentre	AECC	90 days	547	186	50 ± 16	227 (41.5%)	APACHE III score, tidal volume	Day 0
Calfee 2012 [65]	RCT (FACTT)	Multicentre	AECC	90 days	931	261	50 ± 16	498 (53.5%)	Age, APACHE III score, fluid management strategy	Day 0
Calfee 2015 [66]	Prospective cohort	Single centre	AECC	Hospital	100	31	58 ± 11	52 (52.0%)	APACHE III score	Day 2 following ICU admission
Calfee 2015 [66]	RCT (FACTT)	Multicentre	AECC	90 days	853	259	51 ± 15	444 (52.1%)	APACHE III score	Within 48 h following ARDS onset
Cartin-Ceba 2015 [67]	Prospective cohort	Single centre	AECC	In-hospital	100	36	62.5 (51–75 IQR)	54 (54.0%)	Acute physiology score of APACHE III score, DNR status, McCabe score	Within 24 h following diagnosis
Chen 2009 [68]	Prospective cohort	Single centre	*	28 days	59	26	62 ± 19	35 (59.3%)	APACHE II score, biomarkers	Within 24 h following diagnosis
Clark 1995 [69]	Prospective cohort	Single centre	**	Mortality	117	48	43.4 ± 15.4	75 (64.1%)	Lung injury score, risk factor for ARDS, lavage protein concentration	Day 3 following disease onset
Clark 2013 [70]	RCT (FACTT)	Multicentre	AECC	60 days	400	106	47 (37–57 IQR)	210 (52.5%)	Age, gender, ethnicity, baseline serum creatinine, ARDS risk factor	Day 1 following inclusion
Dolinay 2012 [71]	Prospective cohort	Single centre	AECC	In-hospital	28	17	54 ± 14.5	13 (46.4%)	APACHE II score	Within 48 h following ICU admission
Eisner 2003 [72]	RCT (ARMA)	Multicentre	AECC	180 days	565	195	51 ± 17	332 (58.8%)	Ventilation strategy, APACHE III score, PaO₂/FiO₂, creatinine, platelet count	Day 0 following inclusion
Forel 2015 [73]	Prospective cohort	Multicentrer	Berlin < 200 mmHg	ICU	51	NR (for ICU)	60 ± 13	40 (78.4%)	Lung injury score	Day 3
Forel 2018 [74]	Prospective cohort	Single centre	Berlin < 200 mmHg	60 days	62	21	59 ± 15	47 (75.8%)	Gender, SOFA score, LIS score	Day 3 following onset of ARDS
Guervilly 2011 [75]	Prospective cohort	Single centre	AECC	28 days	52	21	58 ± 17	39 (75.0%)	Not specified	Within 24 h following diagnosis
Kim 2019 [76]	Retrospective cohort	Single centre	Berlin	In-hospital	97	63	67.2 (64.3–70.1)	63 (64.3%)	APACHE II score, SOFA score, SAPS II score	Within 48 h following admission
Lee 2019 [77]	Retrospective cohort	Single centre	Berlin	In-hospital	237	154	69 (61–74 IQR)	166 (70.0%)	Age, diabetes mellitus, non-pulmonary source, APACHE II score, SOFA	Within 24 h following intubation
Lesur 2006 [78]	Prospective cohort	Multicentre	AECC	28 days	78	29	63 ± 16	48 (61.5%)	Age, PaCO₂, APACHE II score	Within 48 h following onset of ARDS
Li 2019 [79]	Retrospective cohort	Single centre	Berlin	28 days	224	70	64 (46–77 IQR)	140 (62.5%)	APACHE II score, age, gender, BMI, smoking status, alcohol abusing status, risk factors, comorbidities	Within 24 h following ICU admission
Lin 2010 [80]	Prospective cohort	Single centre	AECC ARDS	28 days	63	27	75 (57–83 IQR)	38 (60.3%)	Age, lung injury score, SOFA score, APACHE II score, CRP, biomarkers	Within 24 h following ARDS onset
Lin 2012 [81]	Prospective cohort	Single centre	AECC	30 days	87	27	61 (56–70 IQR)	42 (48.3%)	APACHE II, Lung injury score, creatinine, biomarkers	At inclusion
Lin 2013 [82]	Prospective cohort	Single centre	AECC	30 days	78	22	63 (54–68 IQR)	45 (57.7%)	Age, APACHE II score, Lung injury score, PaO₂/FiO₂	Within 10 h following diagnosis
Madtes 1998 [83]	Prospective cohort	Single centre	***	In-hospital	74	33	38 (19–68 Range)	50 (67.6%)	Age, PCP III levels, neutrophils, lung injury score	Day 3 following ARDS onset
McClintock 2006 [84]	RCT (ARMA)	Multicentre	AECC	Mortality	579	NR	51 ± 17	333 (57.5%)	Ventilator group assignment	Day 0 following inclusion
McClintock 2007 [85]	RCT (ARMA)	Multicentre	AECC	Mortality	576	NR	52 ± 17	328 (56.9%)	Gender, ventilator group assignment, eGFR, age, APACHE III score, vasopressor use, sepsis	Day 0 following inclusion
McClintock 2008 [86]	Prospective cohort	Two centre	AECC	In-hospital	50	21	55 ± 16	28 (56.0%)	Age, gender, SAPS II	Within 48 h following diagnosis
Menk 2018 [87]	Retrospective cohort	Single centre	Berlin	ICU	404	182	50 (37–61 IQR)	265 (65.6%)	Age, gender, APACHE II score, SOFA, severe ARDS, peak airway pressure, pulmonary compliance	Within 24 h following admission
Metkus 2017 [88]	RCT (ALVEOLI, FACTT)	Multicentre	AECC	60 days	1057	NR	50.4	549 (51.9%)	Age, gender, trial group assignment	Within 24 h following inclusion
Mrozek 2016 [89]	Prospective cohort	Multicentre	AECC	90 days	119	42	57 ± 17	82 (68.9%)	Age, gender, SAPS II score, PaO₂/FiO_2, sepsis	Within 24 h following inclusion
Ong 2010 [90]	Prospective cohort	Two centre	AECC	28-day in-hospital	24	NR	51 ± 21	30 (53.6%)	Age, gender, PaO₂/FiO₂, tidal volume, plateau pressure, APACHE II score	At inclusion
Parsons 2005 [91]	RCT (ARMA)	Multicentre	AECC	180 days or discharge	562	196	NR	NR	Ventilation strategy, APACHE III score, PaO₂/FiO₂, creatinine, platelet count, vasopressor use	At inclusion
Parsons 2005 [92]	RCT (ARMA)	Multicentre	AECC	In-hospital	781	276	51.6 ± 17.3	319 (40.1%)	Ventilation strategy, APACHE III score, PaO₂/FiO₂, creatinine, platelet count, vasopressor use	Day 0
Quesnel 2012 [93]	Prospective cohort	Single centre	AECC	28 days	92	37	67 (49–74 IQR)	61 (66.3%)	Age, SAPS II score, malignancy, SOFA score, BAL characteristics	NR
Rahmel 2018 [94]	Retrospective cohort	Single centre	AECC	30 days	119	37	43.7 ± 13.3	71 (59.7%)	Age, SOFA score	Within 24 h following admission
Reddy 2019 [95]	Prospective cohort	Single centre	Berlin	30 days	39	19	55 (47.5-61.5)	25 (64.1%)	Not specified	Within 24 h of ARDS diagnosis
Rivara 2012 [96]	Prospective cohort	Single centre	AECC	60 days	177	70	71.5 (59–80 IQR)	98 (55.4%)	APACHE III score	Within 48 h following diagnosis
Rogers 2019 [97]	RCT (SAILS)	Multicentre	AECC	60 days	683	NR	56 (43–65)	335 (49.0%)	Age, race, APACHE III score, GFR, randomization, shock	Within 48 h following ARDS diagnosis
Sapru 2015 [98]	RCT (FACTT)	Multicentre	AECC	60 days	449	109	49.8 ± 15.6	242 (53.9%)	Age, gender, APACHE III score, pulmonary sepsis, fluid management strategy	Upon inclusion
Suratt 2009 [99]	RCT (ARMA)	Multicentre	AECC	In-hospital	645	222	51 ± 17	381 (59.1%)	Ventilation strategy, age, gender	Day 0
Tang 2014 [100]	Prospective cohort	Multicentre	Berlin	In-hospital	42	20	72.5 ± 10.8	27 (64.3%)	APACHE II score, PaO₂/FiO₂, CRP, WBC, procalcitonin	Within 24 h following diagnosis
Tsangaris 2009 [101]	Prospective cohort	Single centre	AECC	28 days	52	27	66.1 ± 16.9	32 (59.6%)	APACHE II score, age, genotype	Within 48 h following admission
Tsangaris 2017 [102]	Prospective cohort	Single centre	NR	28 days	53	28	64.6 ± 16.8	33 (62.3%)	Lung injury score	Within 48 h following diagnosis
Tsantes 2013 [103]	Prospective cohort	Single centre	AECC	28 days	69	34	64.4 ± 17.9	43 (62.3%)	Age, gender, APACHE II score, SOFA score, pulmonary parameters, serum lactate	Within 48 h following diagnosis
Tseng 2014 [104]	Prospective cohort	Single centre	AECC ARDS	ICU	56	16	70.6 ± 9.2	31 (55.4%)	APACHE II score, SOFA score, SAPS II score	Day 1 following ICU admission
Wang 2017 [105]	Prospective cohort	Multicentre	Berlin	60 days	167	62	76.5 (19–95 range)	112 (67.1%)	Age, gender, APACHE II score	Day 1 following diagnosis
Wang 2018 [106]	Retrospective cohort	Single centre	AECC	Mortality	247	146	62 (48–73 IQR)	162 (65.6%)	Age, cirrhosis, creatinine, PaO₂/FiO₂	Within 24 h following diagnosis
Ware 2004 [107]	RCT (ARMA)	Multicentre	AECC	In-hospital	559	193	51 ± 17	332 (59.4%)	Ventilator strategy, APACHE III score, PaO₂/FiO₂, creatinine, platelet count	Day 0 of inclusion
Xu 2017 [108]	Retrospective cohort	Single centre	Berlin	28 days	63	27	54 (42–67 IQR)	37 (58.7%)	APACHE II score, PaO₂/FiO₂, procalcitonin	Within 48 following admission
				Total^†	15,344	3914
						36.0%

*Respiratory failure requiring positive pressure ventilation, PF ratio < 200 mmHg, bilateral pulmonary infiltration on chest X-ray, no clinical evidence of left atrial hypertension
**PF ratio < 150 mmHg, PF < 200 mmHg with 5 PEEP, diffuse parenchymal infiltrates, pulmonary artery wedge pressure < 18 mmHg, no clinical evidence of congestive heart failure
***PF ratio < 150 mmHg, PF ratio < 200 mmHg with 5 cmH2O PEEP, diffuse parenchymal infiltrates, pulmonary artery wedge pressure < 18 mmHg, or no clinical evidence of congestive heart failure
^†Some studies included patients from the same cohort
Abbreviations: AECC American European Consensus Conference definition of ARDS, APACHE acute physiology and chronic health evaluation, ARDS acute respiratory distress syndrome, BAL bronchoalveolar lavage, BMI body mass index, CRP C-reactive protein, CVVHD continuous veno-venous haemodialysis, DNR do not resuscitate, ECMO extra corporeal membrane oxygenation, eGFR estimated glomerular filtration rate, FiO₂ fraction of inspired oxygen, ICU intensive care unit, PCP procollagen, No. number, SAPS simplified acute physiology score, SOFA sequential organ failure assessment, WBC white blood cell count

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