Online Supplement. Safety and Outcomes of Prolonged Usual-Care Prone Position Mechanical Ventilation to Treat Acute COVID-19 Hypoxemic Respiratory Failure.

Setting and Care standards.........................................................................................................................2

Supplementary Box: The Best Practice of Proning Project (B-POP / MICU) at Denver Health..............4

Supplementary Figure Legends.................................................................................................................5

Table S1. Concomitantly administered medications.................................................................................6

Table S2. Laboratory values in COVID-19 patients treated with prolonged PPV....................................7

Table S3: Ventilation Duration, Lung Mechanics and Arterial Blood Gases at Time of Initial PPV Episode.......................................................................................................................................................9

Figure S1. PaO2:FiO2 ratios on day 0 and day 3 of mechanical ventilation...........................................10

Figure S2. Oxygenation and Applied PEEP level at Time of Initial Prone Positioning..........................11

Figure S3. Change in oxygenation after prone-to-supine repositioning..................................................12

Figure S4. Complications of prolonged PPV; Maximum Edema Score by Site.....................................13

Table S4: Pressure Wounds.....................................................................................................................14

Table S5. Serious Adverse Events...........................................................................................................15

Table S6. Rates of PPV and hospital mortality amongst published cohorts of mechanically ventilated patients with COVID-19 ARDS..............................................................................................................16

Table S7a. Predictors of hospital mortality, Unit OR (95% CI), SOFA scores.......................................17

Table S7b. Predictors of hospital mortality, Unit OR (95% CI), PF Ratio.............................................17

Table S7c. Predictors of time to hospital death, Cox Proportional Model, SOFA scores.......................18

Table S7d. Predictors of time to hospital death, Cox Proportional Model, PF Ratios............................18

Table S7e. Predictors of anterior pressure wounds, Unit OR (95% CI), Logistic regression.................19

Table S7f. Predictors of posterior pressure wounds, Unit OR (95% CI), Logistic regression................19

Supplementary Appendix References......................................................................................................20

Authors: Ivor S. Douglas, Chester A. Rosenthal, Diandra Reed, Terra Hiller, Judy Oakes, Jamie Bach,

Christopher Whelchel, Jennifer Pickering, Tobias George, Mark Kearns, Michael Hanley, Kara Mould,

Sarah Roark, Jason Mansoori, Anuj Mehta, Eric P. Schmidt and Anna Neumeier.

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Setting and Care standards.

Denver Health Medical Center is a 500-bed Level One trauma and acute care community academic

hospital serving the urban under-served of Denver City and County. Intensive Care is delivered using a

closed-management academic, multi-disciplinary model. Consideration for and practice of PPV is

according to an institution-specific ‘Best Practice of Proning (B-POP)” multi-stakeholder policy. The core

components include Identifying Proning Clinical Triggers, Contraindications, Considerations and

Complications of Proning, Communication and Chain of Command, Supplies and Equipment Preparation,

Proning Methods and Care of the Prone Patient including Cardiopulmonary Resuscitation (CPR). The

protocol was developed by a multidisciplinary team and is supported by a robust mandatory on-line

training program. A listing of the training program modules are listed in the Box below. Selected training

videos (chapters 7 and 8) are provided as supplementary online materials

(http://links.lww.com/CCM/G123; and http://links.lww.com/CCM/G124). The complete protocol and

materials are available for individual review on email request to the authors.

A decision to initiate PPV is triggered when a mechanically ventilated patient has persistent severe

hypoxemia (PF Ratio < 150 at sea level, FiO2 > 60% and PEEP > 10cmH2O) despite 2-6 hours

stabilization with conventional LPV in the assist-control mode and with application of PEEP according to

the ARDS Network PEEP:FiO2 table. Volume-cycle ventilation without ATC, Richmond Sedation

Agitation Scale (RASS)-targeted sedation and delirium management, daily SAT and SBT and readiness

for liberation are administered according to a standardized unit-specific protocol and adherence is

overseen by the lead RT each shift. Extra-corporeal life support (ECLS) options were not available at

DHMC during the period of this study. 1 patient was transferred during this period for intractable

hypoxemia and consideration for ECLS.

Prone positioning was performed according to a unit standard and with trained provider teams.

Repositioning to the prone or supine position was performed manually and positioning was achieved with

S2

foam wedges and pillows. Alternating arm repositioning in the “swimming position” was performed

every 2 hours as tolerated. Return to the supine position was only performed in the event of an invasive or

imaging procedure, cardiopulmonary arrest necessitating chest compressions or when the patient was

determined to have stable gas exchange while ventilated with FiO2 <60% and with PEEP <10cmH20 for

at least 4 hours. Sedation, analgesia and neuromuscular blockade were administered according an

evidence-based protocol and was titrated to achieve deep sedation (Richmond Sedation Agitation Scale

score of 4-5). Sedation awakening, spontaneous breathing trials and ventilator liberation were similarly

performed per protocolized usual care standard and progress was reviewed twice daily by the

multidisciplinary ICU team. Pressure wounds were recorded daily by bedside staff according to the

National Pressure Ulcer Advisory Panel’s Updated Pressure Ulcer Staging System (NPUAP).(1)

Usual care practices require daily assessment of risk for VTE and stress ulceration with appropriate

prophylaxis when indicated. Daily assessment for readiness to wean and liberate from mechanical

ventilation are also performed in a protocol-supervised fashion with monthly reporting on performance

and compliance.

COVID-19 specific therapies were administered either per institutional consensus care-standard or as

proscribed in clinical research protocols to which patients were randomized (Supplementary Appendix,

Table S1.)

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Supplementary Box: The Best Practice of Proning Project (B-POP / MICU) at Denver Health

S4

This Educational Curriculum from the Best Practice of Proning Project on the Medical ICU at Denver Health is intended to help our staff, especially in times like the pandemic, to truly refine our proning skills. We aim to give our staff a support platform based on sound research and collaborative work to help care for our patients who make this all possible.

Chapter 1: Introduction to the Best Practices in Proning Project Training Hours: 11 min

Chapter 2: Standard Method - Making a Proning Kit Training Hours: 1 min

Chapter 3: Standard Method - Supply Preparation Training Hours: 3 min

Chapter 4: Target Method - Making a Proning Kit Training Hours: 1 min

Chapter 5: Target Method - Supply Preparation Training Hours: 5 min

Chapter 6: Bed Preparation Stryker Isolibrium In-Touch ICU Beds Training Hours: 4 min

Chapter 7: Patient Preparation Training Hours: 7 min ONLINE VIDEO 1 (http://links.lww.com/CCM/G123).

Chapter 8: Standard Method of Proning Training Hours: 7 min ONLINE VIDEO 2 (http://links.lww.com/CCM/G124).

Chapter 9: Standard Method Swimming Training Hours: 4 min

Chapter 10: Standard Method - SupiningTraining Hours: 3 min

Chapter 11: Standard Method - Morbid Obese Prone Training Hours: 4 min

Chapter 12: PLACE and S.E.T. The Mölnlycke Tortoise Turning and Positioning System Training Hours: 5 min

Chapter 13: "S.E.T." the Tortoise at Denver Health Training Hours: 2 min

Chapter 14: How to prone with Mölnlycke® Tortoise®Turning and positioning

Training Hours: 11 min

Chapter 15: Target Method - Tortoise Proning at Denver Health Training Hours: 5 min

Chapter 16: Target Method - Lateral Rotation Training Hours: 5 min

Chapter 17: Target Method - Final Adjustments Training Hours: 2 min

Chapter 18: Target Method - Swimming Training Hours: 6 min

Chapter 19: Hill-Rom Viking Mobile Lift - Operating the Lift Training Hours: 4 min

Chapter 20: Tortoise with Portable Lifts Training Hours: 6 min

Supplementary Figure Legends

Figure S1. PaO2:FiO2 ratios on day 0 and day 3 of mechanical ventilation.

Figure S2. Oxygenation and Applied PEEP level at Time of Initial Prone Positioning

Figure S3. Change in oxygenation after prone-to-supine repositioning

Figure S4. Complications of prolonged PPV; Maximum Edema Score by Site

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Table S1. Concomitantly administered medications

Survived (42) Died (19) All (61)Azithromycin, n (%) 28 (45.9%) 9 (14.8%) 37 (60.7%)Hydroxychloroquine/Placebo (Orchid RCT),n (%) NCT04332991 3 (4.9%) 0 (0%) 3 (4.9%)Hydroxychloroquine Open Label, n (%) 27 (44.3%) 10 (16.4%) 37 (60.7%)Tocilizumab/Placebo (Covacta RCT), n (%) NCT04320615 8 (13.1%) 3 (4.9%) 11 (18%)Tocilizumab Open Label, n (%) 10 (16.4%) 4 (6.6%) 14 (23%)Remdesivir/Placebo (ACTT1 RCT) , n (%)NCT04280705 10 (16.4%) 0 (0%) 10 (16.4%)Baricitinib/Placebo + Remdesivir Open label (ACTT2 RCT) , n (%)NCT04401579 2 (3.3%) 0 (0%) 2 (3.3%)Remdesivir Open Label, n (%) 7 (11.5%) 4 (6.6%) 11 (18%)Alteplase 50mg (STARS RCT) , n (%)NCT04357730 1 (1.6%) 0 (0%) 1 (1.6%)COVID-19 convalescent plasma EUA, n (%) 3 (4.9%) 3 (4.9%) 6 (9.8%)High dose Glucocorticoids

DexamethasonePrednisone

Methylprednisolone

7 (11.5%)3 (4.9%)3 (4.9%)1 (1.6%)

1 (1.6%)0 (0%)

1 (1.6%)0 (0%)

8 (13.1%)3 (4.9%)4 (6.6%)1 (1.6%)

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Table S2. Laboratory values in COVID-19 patients treated with prolonged PPV.

Initial Value Minimum Value Maximum ValueSurvived

(42)Died (19) All (61) Survived (42) Died (19) All (61) Survived

(42)Died (19) All (61)

Sodium 138 (4.4) 138.3 (7) 138.1 (5.3) 132.6 (3.4) 130.9 (5.6) 132 (4.3) 147 (3) 147.8 (4) 147.3 (3.4)Potassium 3.8 (0.4) 4.1 (0.7) 3.9 (0.5) 3.1 (0.3) 3.3 (0.3) 3.2 (0.3) 5 (0.9) 5.6 (0.8) 5.2 (0.9)Chloride 104.3 (4.7) 104.6 (7.4) 104.4 (5.7) 97.1 (4) 96.1 (7.3) 96.8 (5.3) 112.8 (3) 113.9 (3.8) 113.1 (3.3)BUN 15.8 (7.5) 24 (16.3) 18.5 (11.7) 8.5 (3.6) 16.3 (9.4) 11.1 (7.1) 44.2 (28.9) 87.3 (41.7) 58.3 (39)CO2 23 (3.8) 23.1 (2.4) 23 (3.4) 19.3 (2.9) 17 (4.6) 18.5 (3.7) 32.6 (3.5) 29.9 (3.8) 31.7 (3.8)Creatinine 0.9 (0.3) 1.6 (2) 1.2 (1.2) 0.5 (0.2) 1 (0.9) 0.7 (0.6) 1.8 (1.8) 4.3 (5.6) 2.6 (3.7)Anion Gap 10.7 (4.1) 10.6 (3.4) 10.7 (3.9) 4.1 (1.9) 4.4 (2.1) 4.2 (2) 15.1 (3.6) 16.9 (5.4) 15.7 (4.3)Calcium 8.6 (0.7) 8.7 (0.7) 8.6 (0.7) 7.2 (0.5) 6.9 (0.5) 7.1 (0.5) 9.3 (0.6) 9.4 (1.1) 9.3 (0.8)Phosphorus 3.4 (1.8) 3.8 (2) 3.5 (1.8) 2.3 (0.7) 2.6 (0.9) 2.4 (0.8) 5.7 (3.4) 6.2 (3) 5.8 (3.2)Albumin 3.7 (0.6) 3.7 (0.3) 3.7 (0.5) 2.7 (0.4) 2.5 (0.4) 2.6 (0.4) 4.2 (0.4) 4 (0.5) 4.1 (0.4)ALP 96.9 (39.8) 102.4 (32.7) 98.7 (37.4) 71.7 (26.3) 73.8 (22) 72.3 (24.8) 205.8

(131.1)208.9 (124) 206.8

(127.8)ALT 50.2 (33.9) 53.4 (41.9) 51.2 (36.4) 22.8 (12.1) 25.3 (13.8) 23.6 (12.6) 122 (96.2) 124 (127.9) 122.6

(106.6)AST 53.9 (44.3) 51.7 (35.7) 53.2 (41.4) 24 (15.5) 29.9 (19.6) 25.9 (17) 129.7 (80.7) 267.6

(436.2)174.9

(262.4)Bilirubin, Direct

0.5 (1) 0.3 (0.2) 0.4 (0.8) 0.3 (0.4) 0.2 (0.2) 0.3 (0.3) 1.2 (1.3) 2.5 (4.5) 1.6 (2.8)

Bilirubin, Total 0.8 (1.2) 0.7 (0.5) 0.8 (1) 0.4 (0.4) 0.5 (0.4) 0.4 (0.4) 1.8 (1.6) 4.4 (8.9) 2.6 (5.3)LDH 440.6 (140.9) 596.2

(388.8)484.6

(244.6)350.4 (131.8) 536.8 (385) 403.2

(243.8)471.6

(138.3)668.9

(433.7)527.4

(268.9)

Auto WBC 9.4 (3.9) 8 (3) 8.9 (3.7) 5.4 (1.6) 5 (2.1) 5.3 (1.8) 18.9 (9.3) 25.8 (14.7) 21.1 (11.7)Hematocrit 44.1 (5.1) 44.4 (6.7) 44.2 (5.6) 28.4 (5.6) 30.1 (6.5) 29 (5.9) 46.4 (3.4) 47.1 (5.2) 46.6 (4.1)MCV 90.5 (5.9) 91.6 (5.9) 90.9 (5.9) 87.7 (5.5) 88.4 (4.8) 88 (5.2) 98.3 (6.3) 100 (7) 98.9 (6.5)Platelets 242 (84.1) 213.4 (84.9) 232.6 (84.7) 165 (57.5) 135.3 (55.9) 155.3 (58.2) 547.5

(159.8)396.1

(207.9)497.9

(189.4)Abs. Lymphs 1.6 (0.8) 1.3 (0.7) 1.5 (0.8) 0.8 (0.3) 0.9 (0.4) 0.8 (0.4) 2.1 (0.6) 1.7 (1.1) 2 (0.9)Abs. PMN 6.7 (3.3) 5.9 (2.6) 6.5 (3.1) 4.4 (2.1) 5 (2.8) 4.6 (2.4) 11.1 (5) 13.5 (7.4) 11.9 (6)Granulocytes 1 (1.2) 1 (0.7) 1 (1.1) 0.6 (0.7) 0.8 (0.7) 0.7 (0.7) 2.8 (1.4) 2.7 (1.6) 2.7 (1.5)

FIO2 79.6 (28.5) 92.3 (19.6) 83.8 (26.4) 32.4 (12.1) 46.3 (15.8) 37 (14.8) 96.1 (8.6) 98 (6.2) 96.7 (7.9)SaO2 93.8 (3.9) 92.1 (5.5) 93.2 (4.6) 84.8 (5.7) 79.7 (11.8) 83.1 (8.5) 99 (1.1) 98.8 (1.1) 98.9 (1.1)PaCO2 38 (7.7) 39.7 (8.6) 38.6 (8) 31.8 (4.8) 32.8 (4.9) 32.2 (4.8) 69.5 (30.2) 68.5 (22.6) 69.2 (27.7)

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PaO2 81.4 (32.7) 75.9 (24.4) 79.6 (30.1) 51.8 (8.4) 48.5 (8.1) 50.7 (8.4) 166.3 (61.3) 147 (48.5) 160 (57.7)Base Excess -0.2 (5.4) -2.6 (5) -1 (5.3) -3.5 (3.6) -8.3 (6.6) -5 (5.3) 8.4 (4.4) 4.2 (4.8) 7 (4.9)Lactate 2.8 (3.3) 3.1 (3.5) 2.9 (3.3) 1.2 (0.3) 1.4 (0.6) 1.2 (0.4) 3.2 (3.3) 4.9 (4.1) 3.8 (3.7)

CRP 151.4 (99.3) 141.4 (116.9)

148.1 (104.5)

100.7 (93.8) 121 (101.8) 107.3 (96.1) 250.6 (86.5) 261.1 (105.4)

254.1 (92.4)

D-Dimer 3.2 (5) 4.4 (6.2) 3.6 (5.4) 2.7 (4.7) 2.6 (2.5) 2.7 (4.1) 7.5 (6.5) 6.4 (4.7) 7.2 (5.9)Ferritin 943.7 (753) 1050

(1124.6)977.3 (879) 601.9 (497.2) 816.7

(820.3)669.9

(618.9)1379.5

(1066.7)1505.1

(1103.2)1419.2

(1070.6)Triglycerides 263.4 (219.7) 205.1 (81.5) 246 (190.4) 166.3 (92.8) 176.7 (70.8) 169.4 (86.3) 401.4

(259.8)358.8

(220.9)388.7

(247.6)aPTT 56.9 (54.5) 38.9 (15.8) 50.4 (45) 40.5 (33.5) 35.1 (7.2) 38.5 (27) 116.5 (71.5) 87.9 (47.9) 106.1 (64.9)

Glucose POC 181.4 (133.6) 199 (115.6) 187.9 (126.4)

81.6 (27.1) 93.8 (35.3) 86.1 (30.6) 267.4 (131.5)

293.4 (146.2)

276.9 (136.2)

Glucose, lab 141.4 (119.7) 150.3 (62.6) 144.3 (103.9)

79.6 (17) 90.6 (35.1) 83.2 (24.7) 279.9 (153.8)

322.5 (139.5)

293.8 (149.4)

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Table S3: Ventilation Duration, Lung Mechanics and Arterial Blood Gases at Time of Initial PPV Episode.

Pre PPV Post PPVMedian (IQR) Survived (42) Died (19) All (61) Survived Died AllTime to PPV (d) 0.25 (0.09, 0.79) 0.35 (0.15, 0.89) 0.28 (0.11, 0.80)1st PPV episode duration (d) 2.95 (1.8, 5.0) 3.3 (2.4, 6.6) 2.95 (1.9, 5.1)FiO2 (%) 80 (60, 97.5) 80 (72.5, 100) 80 (70, 100)MAP (cmH2O) 18 (16, 21.5) 22 (16.3, 24) 19 (16, 22)Min Ventilation (L/min) 10.6 (9.1, 12.3) 10.2 (9.1, 12.7) 10.4 (9.1, 12.4)PIP (cmH2O) 31 (27, 35) 34.5 (29.3, 39.8) 32 (27.5, 36)PPlateau (cmH2O) 27 (23, 29.5) 28.5 (21.3, 30.8) 27 (22, 30)PEEP/CPAP (cmq22) 14 (12, 18) 16 (14, 18) 14 (12, 18)Pdrive (Ppl-PEEP) 12 (9.5, 14) 10.5 (9, 13.8) 11 (9, 14)Resp Rate 26 (20, 32) 27.5 (22.5, 30) 26 (22, 31.8)Vt (Set, mL) 400 (350, 420) 400 (342.5, 435.3) 400 (350, 420)pH 7.39 (7.34, 7.42) 7.36 (7.32, 7.41) 7.38 (7.33, 7.42) 7.36 (7.33, 7.4) 7.34 (7.24, 7.39) 7.36 (7.31, 7.39)PaCO2 43 (39, 51.5) 43 (36, 49.3) 43 (37, 50.5) 47 (42.5, 52) 43 (37, 48.8) 46 (41, 51.5)PaO2 73 (65, 89) 92 (66, 107) 76 (65, 97) 99 (83.5, 140) 88 (74.8, 118.8) 96 (79, 128)FiO2 90 (70, 100) 100 (73, 100) 100 (70, 100) 90 (70, 100) 80 (63, 100) 80 (70, 100)P/F ratio 95.6 (72, 131.3) 102.9 (84.6, 116.6) 99 (73, 128) 144 (104.6,

167.9)129 (101.9,

146.9)135.7 (104.6,

163.8)SaO2 94 (90, 97) 96 (92, 98) 95 (91, 98) 97 (96, 99) 95 (94, 98) 97 (95, 99)

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Figure S1. PaO2:FiO2 ratios on day 0 and day 3 of mechanical ventilation.

* Mean difference -9.632 (95%CI: -48.3,0.0, P=0.05) vs. Survived d3 † Mean difference 17.5952 (95%CI: 16.6, 54.1, P=0.05) vs. Survived d0

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*

†

Figure S2. Oxygenation and Applied PEEP level at Time of Initial Prone Positioning

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Figure S3. Change in oxygenation after prone-to-supine repositioning

SaO2:FiO2 (SF) ratio immediately prior to and within 90 min of prone-to-supine repositioning (69 repositioning episodes amongst 50 patients). Box and whisker plots indicate median, 25th and 75th percentiles. Prone: 196 (186, 238) to Supine: 186 (152, 213), P = 0.008. Black pairs: SF ratio increased or a decreased < 50; Red pairs: SF ratio decrease of ≥ 50.

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Figure S4. Complications of prolonged PPV; Maximum Edema Score by Site

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Table S4: Pressure Wounds

Wound location N (%)Any Wounds 43 (70.49%)Scattered 4 (6.56%)

Ventral wounds from PPV 40 (65.6)%Chest 3 (4.92%)Abdomen 9 (14.75%)Perineum, groin and scrotum 15 (24.59%)

Dorsal Wounds 12 (19.67%)Back 4 (6.56%)Sacrum/buttocks 9 (14.75%)Posterior neck 2 (3.28%)

Head and NeckEars 17 (27.87%)Face, Chin, Nose and Neck 27 (44.26%)Axilla 2 (3.28%)

ExtremitiesLower extremities 12 (19.67%)Upper extremities 16 (26.23%)

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Table S5. Serious Adverse Events

N % of TotalInfections

CAUTI 5 8.2%CLABSI 3 4.9%HA-CDI 1 1.6%VTE 4 6.6%

Airway/ventilation complicationsThick mucus plugs 17 27.9%Emergent escalation +/- bronch for mucus plug

11 18.0%

Reintubation 8 13.1%ETT Repositioned 39 63.9%

CardiovascularMAP < 65 > 10 times 27 44.3%

Integument and neuromuscular4 extremity weakness 58 95.1%Grade IV Pressure Wound 2 3.3%Brachial Plexus Injury 5 8.2%

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Table S6. Rates of PPV and hospital mortality amongst published cohorts of mechanically ventilated patients with COVID-19 ARDS

PPV No PPV Initial SOFA Hospital Mortality*

NY city(2) 35 168 11 (8, 13) > 39.0%Lombardy Italy(3)

240 635 > 26.0%

Brescia, Italy(4) 3 30 3.5 (3, 7) >3.0%Milan(5) 46 27 >23.3%Vitoria-Gasteiz, Spain(6)

22 26 7 (3) >15.0%

San Francisco. (7)

13 6 7.5 (3.5, 7.5) >12.0%

Boston(8) 31 35 >16.7%Seattle(9) 8 7 >52.0%Wuhan1(10) 6 31 5 (4, 6) > 61·5%Wuhan2(11) 7 12Atlanta, Emory(12)

41 176 7 (5, 11) >35.7%

ICNARC UK(13) Not reported >49.0%Denver Health, CO

61 0 4 (3.5, 5.5) >31.1%

*Reported hospital mortality includes only patients who had died at time of the report.SFO Duration 5 (2–10), APII 15 (12, 18) correlates with initial SOFA score of 7.5MGH Duration 18 hours (IQR, 16–22 h) Emory U. Mortality amongst PPV was 59% (Personal communication, S Auld)

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Table S7a. Predictors of hospital mortality, Unit OR (95% CI), SOFA scores

Term Unit Odds Ratio

Lower 95%

Upper 95%

P-Value

1st SOFA Score 2.294 1.442 4.282 0.0004Delta SOFA d0-3 1.702 1.184 2.654 0.003Age 1.100 1.025 1.201 0.007Max Value Ferritin 1.000 0.999 1.000 NSMin Abs. Lymphs 2.381 0.273 24.319 NSPdrive (Ppl-PEEP) 1.060 0.882 1.267 NSAdmission BMI 1.017 0.912 1.121 NS1st SOFA Score 2.294 1.442 4.282 NSDelta SOFA d0-3 1.702 1.184 2.654 NSModel Performance: BIC 77.37; Pearson χ2 27.83; R2 0.38; P 0.0002.

Table S7b. Predictors of hospital mortality, Unit OR (95% CI), PF Ratio

Term Unit Odds Ratio

Lower 95%

Upper 95%

P-Value

Age 1.116 1.040 1.220 0.0012d3 PFR 0.981 0.962 0.999 0.0379Min Abs. Lymphs 5.715 0.902 44.530 NS1st PFR 0.983 0.960 1.003 NSMax Value Ferritin 1.000 0.999 1.000 NSPdrive (Ppl-PEEP) 1.091 0.920 1.300 NSAdmission BMI 1.020 0.915 1.125 NSAge 1.116 1.040 1.220 NSd3 PFR 0.981 0.962 0.999 NSModel Performance: BIC 84.78; Pearson χ2 20.43; R2 0.28; P 0. 0047.

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Table S7c. Predictors of time to hospital death, Cox Proportional Model, SOFA scores

Term Risk Ratio Lower 95%

Upper 95%

P-Value

Age 1.069 1.014 1.133 0.0131st SOFA Score 1.478 1.165 1.855 0.002Delta SOFA d0-3 1.281 1.026 1.613 0.029Min Abs. Lymphs 1.837 0.449 7.631 NSPdrive (Ppl-PEEP) 1.088 0.994 1.190 NSAdmission BMI 1.012 0.931 1.084 NSMax Value Ferritin 1.000 0.999 1.000 NSModel Performance: BIC 135.84; Pearson χ2 21.74; P 0. 0028.

Table S7d. Predictors of time to hospital death, Cox Proportional Model, PF Ratios

Term Risk Ratio Lower 95%

Upper 95%

P-Value

Age 1.122 1.045 1.205 0.0002Pdrive (Ppl-PEEP) 1.202 1.041 1.389 0.0069d3 PFR 0.974 0.954 0.994 0.00771st PFR 0.978 0.959 0.996 0.0094Min Abs. Lymphs 4.380 1.249 15.363 0.0271Max Value Ferritin 1.000 0.999 1.000 NSAdmission BMI 1.025 0.952 1.105 NSModel Performance: BIC 133.71; Pearson χ2 27.95; P 0. 0005.

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Table S7e. Predictors of anterior pressure wounds, Unit OR (95% CI), Logistic regression

Term Unit Odds Ratio

Lower 95%

Upper 95%

PValue

PPV time (d) 1.349 1.091 1.666 <0.001d3 SOFA Score 0.727 0.510 1.036 0.0671st SOFA Score 1.210 0.866 1.692 NSAdmission BMI 0.957 0.883 1.036 NSAge 0.972 0.919 1.027 NSMV time total (d) 0.973 0.921 1.029 NSBraden Scale (Min) 1.093 0.640 1.864 NSModel Performance: BIC 94.96; Pearson χ2 16.48; R2 0.21; P 0. 021.

Table S7f. Predictors of posterior pressure wounds, Unit OR (95% CI), Logistic regression

Term Unit Odds Ratio

Lower 95%

Upper 95%

PValue

d3 SOFA Score 0.553 0.304 1.004 0.015Braden Scale (Min) 0.655 0.374 1.149 NSAdmission BMI 0.927 0.819 1.049 NS1st SOFA Score 1.150 0.826 1.601 NSMV time total (d) 1.013 0.948 1.083 NSAge 1.014 0.942 1.093 NSPPV time (d) 1.015 0.869 1.185 NSModel Performance: BIC 78.75; Pearson χ2 14.63; R2 0.24; P 0. 041.

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