Calculation of O2 content, CO2 content, O2 transfer and CO2 transfer

• O2 content (mL O2/dL dl blood) = 1.34 * (Hb) * SaO2 + 0.0031 * PO2. The factor

1.34 is specified in ml*g-1 and the factor 0.0031 is specified in ml*dLl-1*mmHg-1.

- • CO2 content (mL CO2/dL dl blood) = 22.4 * (HCO3 ) + 0.030 * PCO2. The factor

22.4 (molecular volume of a gas) is specified in Ll*mol-1, and the factor 0.030 is

specified in mM*mmHg-1.

• O2 transfer (ml/min) = ((O2 content)out – (O2 content)in) * blood flow * 10;

• CO2 transfer (ml/min) = ((CO2 content)in – (CO2 content)out) * blood flow * 10.

• The respective values were collected at the inlet (in) and outlet (out) of the

MO.

3-dimensional curve fitting model

O2 transfer and CO2 elimination in relation to blood flow and sweep gas flow were put into a 3-dimensional (3d) curve-fitting model and depicted accordingly. TableCurve 3D (3D v4.0) automated surface fitting analysis software (SYSTAT Software Inc, Systat Software

Inc, San Jose, CA) was used to find equations to describe the three dimensional empirical data. Equation 531 belongs to the x-y polynomial equations and is a Cosine

Series Bivariante Polynominal where Z = a+ b*cos(x) + c*cos(y) + d*cos(2x) + e*cos(x)*col(y) + f*col(2y) with x = BF, y = GF, Z = CO2 transfer adjusted to gas exchange surface.

Statistical analysis

Intergroup differences (comparing 4 different ECMO-systems) were analysed by linear mixed models, while the correlation structure between repeated measurements was specified as unstructured. All models are controlled for type of system, type of system*time, blood flow and gas flow. These analyses were done with SAS 9.3 procedure PROC MIXED (SAS Institute, Cary, NC, USA). Post-hoc pairwise comparisons were adjusted by the Tukey-Kramer method. Statistical significance was assumed if p<0.05.

ESM tables

Table S1 Overview of cannulation modes

ECMO-system All PLS CH HL ECC

Patients (n) 317 163 59 56 39

Direction of blood flow (n, %) outflow > inflow

Femoral vein 213 (67) 106 (65) 48 (81) 40 (71) 19 (49) > jugular vein

Femoral vein 38 (12) 28 (17) 4 (7) 3 (5) 3 (8) > subclavian vein

Femoral vein 7 (2) 5 (3) 1 (2) 0 (0) 1 (3) > Femoral vein

Jugular vein, Bicaval Dual Lumen 49 (15) 22 (13) 6 (10) 11 (20) 10 (26) catheter

Femoral vein, 10 (3) 2 (1) 0 (0) 2 (4) 6 (15) Dual Lumen catheter

PLS = PLS -system, CH = Cardiohelp -system, HL = Hilite 7000 LT –system and

ECC = ECC.05 –system. Table S2: Overview of cannula sizes

ECMO-system All PLS CH HL ECC

Diameter of cannula (Fr) outflow > inflow

Femoral vein 19-25 19-25 21-23 21-23 21-23 > jugular vein >15-23 > 15-23 > 15-21 > 15-19 > 15-21

Femoral vein 21-23 21-23 21 21-22 21-23 > subclavian vein >15-21 > 15-17 > 17-21 > 17 > 17

Femoral vein 21-23 21-23 23 23 -- > Femoral vein >17-23 > 17-23 > 21 > 21

Jugular vein, 23-31 23-31 27 23-27 23-31 Dual Lumen catheter

Femoral vein, 24 24 -- 24 24 Dual Lumen catheter

PLS = PLS -system, CH = Cardiohelp -system, HL = Hilite 7000 LT –system and

ECC = ECC.05 –system. Table S3: CO2 transfer and O2 transfer during study period

Day CO2 transfer CO2 transfer norm O2 transfer O2 transfer norm

(p=0.014) (p=0.002) (p=0.885) (p=0.881)

1 180.6 (174.8, 186.3) 111.1 (107.7, 114.5) 140.5 (136.4, 144.6) 86.4 (84.0, 88.8)

2 173.6 (167.7, 179.4) 106.3 (102.9, 109.7) 141.9 (137.7, 146.0) 86.9 (84.4, 89.3)

3 170.0 (164.0, 176.1) 103.5 (100.0, 107.1) 142.4 (138.1, 146.7) 87.5 (85.0, 90.0)

4 169.2 (162.7, 175.6) 103.0 (99.2, 106.8) 142.2 (137.7, 146.8) 87.2 (84.5, 89.8)

5 170.8 (163.9, 177.7) 104.7 (100.6, 108.7) 140.9 (136.1, 145.7) 86.2 (83.5, 89.0)

Data show least squares means (95%-CI) estimated by linear mixed models. All models are controlled for type of system, type of system*time, blood flow and gas flow. CO2/O2 transfer norm: CO2/O2 transfer adjusted for exchange surface of the

MO. Table S4: CO2 transfer and O2 transfer of 4 different ECMO systems

System PLS CH HL ECC

200.6 (195.6, 167.1 (158.5, 169.7 (161.3, 154.0 (143.6, CO2 TF 205.7) a 175.6) 178.0) 164.3)

CO2 TF 111.4 (108.5, 128.7 (122.8, 92.9 (88.0, 97.8) 89.9 (85.1, 94.6) norm 114.3) c 134.6) b

149.4 (145.4, 142.6 (135.9, 141.3 (134.7, 133.0 (124.9, O2 TF 153.4) 149.3) 147.9) 141.2) d

O2 TF 110.4 (105.7, 83.0 (80.7, 85.3) f 79.2 (75.3, 83.1) 74.7 (70.8, 78.5) norm 115.2) e

CO2/O2 TF = CO2/O2 transfer. CO2/O2 TF norm: CO2/O2 transfer adjusted for exchange surface of the MO. PLS = PLS -system, CH = Cardiohelp -system, HL =

Hilite 7000 LT –system and ECC = ECC.05 –system. Data show least squares means (95%-CI) estimated by linear mixed models. All models are controlled for time, type of system*time, blood flow and gas flow. Pairwise comparisons showed: a =

PLS > ECC/CH/HL (p≤0.001 each); b = ECC > PLS/CH/HL (p<0.001); c = PLS >

CH/HL (P<0.001 each); d = ECC < PLS (p=0.002); e = ECC > PLS/CH/HL (p<0.001 each); f = PLS > HL (p=0.002); no significant differences in the remaining comparisons. Table S5: Parameters at the inlet of the oxygenator

ECMO-system All PLS CH HL ECC

b,c pvO2 (mmHg), 38 (34/41) 37 (34/41) 39 (35/42) 39 (35/42) 38 (35/42) day 1-5

b,d pvCO2 45 (40/50) 45 (40/50) 47 (42/52) 45 (40/48) 45 (41/50)

(mmHg), day1-5 vpH, 7.40 7.39 7.40 7.39 7.41 day 1-5 (7.35/7.44) (7.35/7.43) (7.37/7.45) (7.35/7.43) (7.37/7.45)

e,b

Hb (g/dl), 9.3 9.2 9.5 9.4 9.0 day 1-5 (8.6/10.2) (8.6/10.2) (8.7/10.8) a,b (8.6/10.1) (8.4/9.8)

Parameters displayed as median and interquartile range. PLS = PLS -system, CH =

Cardiohelp -system, HL = Hilite 7000 LT –system and ECC = ECC.05 –system. pvO2

= venous oxygen tension before ECMO; pvCO2 = venous carbon dioxide tension before ECMO; vpH = venous pH before ECMO; Hb = hemoglobin. p ≤ 0.05: a = CH vs ECC; b = CH vs PLS; c = HL vs PLS; d = CH vs HL; e = ECC vs PLS. Legends for ESM figures

Figure S1

CO2 transfer adjusted to the MO exchange surface of different membrane oxygenators

(PLS-system (n = 163; 681 measurements), Cardiohelp (CH) –system (n = 58; 234 measurements), Hilite 7000 LT (HL) -system (n = 56; 255 measurements) and ECC.05- system (n = 40; 161 measurements), 1st to 5th day after ECMO implantation) as fitted

3d-curve (equation 531, Cosine Series Bivariate Order 2, see ESM). Adjusted to the exchange surface of the oxygenator the ECC.05-system was the most effective in terms of CO2 transfer elimination.

Figure S2

Platelet count for each device and the study period in days. PLS = PLS -system, CH

= Cardiohelp -system, HL = Hilite 7000 LT –system and ECC = ECC.05 –system. p < 0.05 (*, CH system; §, ECC system; #, HL system; &, PLS system) compared to values before ECMO (time 0).