Extravascular lung water volume measurement by a novel lithium-thermal indicator dilution method: Comparison of three techniques to gravimetry

Benjamin Maddison, Riccardo Giudici, Enrico Calzia, Christopher Wolff, Charles Hinds, Peter Radermacher and Rupert M. Pearse.

Supplementary results file

Timepoint / Baseline / 2 / 3 / Final / p
Heart Rate (bpm) / 70 (±18) / 114 (± 36) / 97 (± 46) / 95 (±51) / 0.12
Mean Arterial Pressure (mmHg) / 94 (±11) / 91 (±11) / 87 (± 14) / 76(±17) / <0.05
Cardiac Output
(l min-1) / 4.3 (±1.1) / 5.4 (± 2.1) / 4.4(± 1.4) / 4.0(± 1.2) / 0.18
pH / 7.55 (± 0.04) / 7.45 (± 0.07) / 7.48 (± 0.05) / 7.46 (± 0.07) / <0.01
PaO2 (mmHg) / 163
(± 12) / 124
(± 21) / 117
(± 22) / 102
(± 33) / <0.0001
PaO2:FiO2 (mmHg) / 465 (±35) / 354 (± 60) / 335 (± 64) / 263 (± 129) / <0.0001
Positive End Expiratory Pressure
(cm H2O) / 10 [10-10] / 10 [10-10] / 10 [10-10] / 10 [10-12] / 0.55
Peak PAW
(cm H2O) / 20 (±2) / 23 (± 4) / 25(± 5) / 28 (±7) / <0.05
Cumulative fluid balance (litres) / 3.4 (± 2) / 7.4(± 5.7) / 9.4 (± 7.7) / 13.5(±6.5) / <0.01

Supplementary Table 1 Physiological data (n=10)

Data presented as mean (SD)or median [IQR].

Timepoint / Baseline / 2 / 3 / Final / p
Li-thermal ITBV
(ml kg-1) / 21.8 (± 3.7) / 22.2 (± 7.8) / 20.6 (± 6.0) / 22.4 (± 6.3) / 0.91
ICG-thermal ITBV
(ml kg-1) / 30.7 (± 8.1) / 28.7 (±3.7) / 28.1 (±3.7) / 27.0 (± 4.3) / 0.61
Single-thermal ITBV
(ml kg-1) / 27.1 (± 7.4) / 23.0 (± 5.0) / 22.4 (±5.9) / 26.4 (± 5.3) / 0.24
Gravimetric EVLW volume
(ml kg-1) / - / - / - / 9.2 (±3.0) / n/a
Li-thermal EVLW volume
(ml kg-1) / 5.9 (±5.1) / 7.4 (±9.0) / 6.6 (±6.2) / 8.9 (±5.3) / 0.78
ICG-thermal EVLW volume
(ml kg-1) / 4.7 (± 2.3) / 6.7 (± 3.4) / 5.5 (± 3.3) / 7.7 (± 3.7) / 0.22
Single thermal EVLW volume
(ml kg-1) / 13.3 (± 6.3) / 12.3 (± 2.1) / 11.5 (± 2.5) / 15.5 (± 4.7) / 0.24

Supplementary Table 2Thoracic fluid volumes (n=10)

Data presented as mean (SD. Li-thermal, Lithium thermal double indicator dilution; ICG-thermal, Indocyanine Green-thermal double indicator dilution; Single-thermal, Single-thermal indicator dilution; ITBV, Intrathoracic Blood Volume; EVLW, Extravascular lung water.

Timepoint / Baseline / 12 hours / 18 hours / 24 hours / p
Heart Rate (bpm) / 78 (±17) / 126 (±32) / 125 (±36) / 127 (±40) / <0.05
Mean Arterial Pressure (mmHg) / 97 (±10) / 94 (±13) / 87 (±18) / 71 (±20) / <0.05
Cardiac Output
(l min-1) / 4.8 (±1.1) / 4.4 (±0.8) / 4.6 (±1.4) / 4.5 (±1.4) / 0.94
pH / 7.54 (± 0.03) / 7.50 (± 0.03) / 7.48 (± 0.05) / 7.44 (± 0.06) / <0.002
PaO2 (mmHg) / 167
(± 15) / 125
(± 27) / 108
(± 14) / 91.5
(± 16) / <0.0001
PaO2:FiO2 (mmHg) / 477 (± 42) / 358 (± 78) / 310 (± 39) / 234 (± 79) / <0.0001
Positive End Expiratory Pressure
(cm H2O) / 10 [10-10] / 10 [10-10] / 10 [10-10] / 12 [10.5-12] / 0.55
Peak PAW
(cm H2O) / 21 (± 2) / 19 (± 1) / 27 (± 4) / 31 (± 7) / <0.01
Cumulative fluid balance (litres) / 4.8 (± 0.9) / 11.5 (± 3.0) / 14.8 (± 4.3) / 17.8 (± 4.6) / <0.0001

Supplementary Table 3Physiological variables for the sepsismodel (n=6)

Data presented as mean (SD)or median [IQR].

Timepoint / Baseline / 1 hour / 4 hours / 8 hours / p
Heart Rate (bpm) / 59 (±17) / 95 (±38) / 55 (±18) / 47 (±7) / <0.05
Mean Arterial Pressure (mmHg) / 89 (±12) / 86 (±8) / 88 (±7) / 84 (±9) / 0.87
Cardiac Output
(l min-1) / 3.7 (±1.1) / 5.5 (±1.1) / 5.1 (±3.8) / 3.9 (±1.5) / 0.61
pH / 7.55 (± 0.05) / 7.38 (± 0.06) / 7.48 (± 0.08) / 7.49 (± 0.08) / <0.05
PaO2 (mmHg) / 157
(± 2) / 122
(± 7) / 131
(± 28) / 119
(± 48) / 0.26
PaO2:FiO2 (mmHg) / 448 (± 7) / 347 (± 22) / 374 (± 80) / 305 (± 187) / 0.3
Positive End Expiratory Pressure
(cm H2O) / 10 [10-10] / 10 [10-10] / 10 [10-10] / 10 [10-10] / 0.55
Peak PAW
(cm H2O) / 19 (±2) / 19 (± 1) / 20 (± 1) / 22(±4) / 0.1
Cumulative fluid balance (litres) / 1.2 (± 0.2) / 1.2 (± 0.2) / 1.2 (± 0.2) / 7.2 (± 1.2) / P<0.0001

Supplementary Table 4Physiological variables for the visceral organ ischaemiamodel (n=4)

Data presented as mean (SD)or median [IQR].

Timepoint / Baseline / 12 hours / 18 hours / 24 hours / p
Li-thermal ITBV
(ml kg-1) / 20.0 (± 3.7) / 17.7 (± 3.5) / 17.0 (± 4.4) / 19.8 (± 5.5) / 0.52
ICG-thermal ITBV
(ml kg-1) / 32.8 (± 8.4) / 30.8 (± 8.6) / 28.8 (± 4.4) / 28.2 (± 4.1) / 0.66
Single-thermal ITBV
(ml kg-1) / 28.5 (± 8.4) / 20.3 (± 2.7) / 20.8 (± 3.2) / 24.6 (± 4.8) / 0.05
Gravimetric EVLW volume
(ml kg-1) / - / - / - / 9.8 (± 3.6) / n/a
Li-thermal EVLW volume
(ml kg-1) / 8.8 (± 4.0) / 12.0 (± 8.4) / 8.5 (± 6.3) / 9.1 (± 6.7) / 0.77
ICG-thermal EVLW volume
(ml kg-1) / 4.9 (± 2.7) / 6.7 (± 3.1) / 5.6 (± 3.5) / 7.9 (± 4.3) / 0.49
Single thermal EVLW volume
(ml kg-1) / 14.0 (± 8.3) / 11.3 (± 1.8) / 10.0 (± 1.3) / 13.5 (± 3.3) / 0.42

Supplementary Table 5Thoracic fluid volumes for the sepsis model (n=6)

Data presented as mean (SD). Li-thermal, Lithium thermal double indicator dilution; ICG-thermal, Indocyanine Green-thermal double indicator dilution; Single-thermal, Single-thermal indicator dilution; ITBV, Intrathoracic Blood Volume; EVLW, Extravascular lung water.

Timepoint / Baseline / 1 hour / 4 hours / 8 hours / p
Li-thermal ITBV
(ml kg-1) / 24.5 (± 3.3) / 29.0 (± 7.6) / 26.0 (± 3.6) / 25.7 (±6.2) / 0.7
ICG-thermal ITBV
(ml kg-1) / 27.5 (± 7.5) / 25.5 (± 1.7) / 27.0 (± 2.4) / 25.5 (±4.7) / 0.9
Single-thermal ITBV
(ml kg-1) / 25.0 (± 6.2) / 27.1 (± 5.1) / 24.7 (± 8.7) / 29.3 (± 5.7) / 0.78
Gravimetric EVLW volume
(ml kg-1) / - / - / - / 8.3 (± 3.1) / n/a
Li-thermal EVLW volume
(ml kg-1) / 1.6 (± 3.1) / 0.4 (± 4.4) / 3.7 (± 5.5) / 8.7 (± 3.9) / 0.07
ICG-thermal EVLW volume
(ml kg-1) / 4.5 (± 2.0) / 6.7 (± 4.5) / 5.4 (± 3.5) / 7.4 (± 3.5) / 0.65
Single thermal EVLW volume
(ml kg-1) / 12.1 (± 1.9) / 13.8 (± 1.8) / 13.8 (± 2.1) / 18.8 (± 5.3) / 0.06

Supplementary Table 6Thoracic fluid volumes for the visceral organ ischaemia model (n=4)

Data presented as mean (SD). Li-thermal, Lithium thermal double indicator dilution; ICG-thermal, Indocyanine Green-thermal double indicator dilution; Single-thermal, Single-thermal indicator dilution; ITBV, Intrathoracic Blood Volume; EVLW, Extravascular lung water.

Supplementary Figure 1 Linear Regression analysis of Li-thermal, ICG-thermal and Single-thermal EVLW versus gravimetric EVLW

Data used from last measurement point (n=10). Dotted lines indicate 95% confidence intervals for gradient. EVLW, extravascular lung water volume; Li-Thermal, lithium thermal double indicator dilution; ICG-thermal, indocyanine green-thermal double indicator dilution; Single-thermal, single thermal indicator dilution.

Supplementary Figure 2 Bland-Altman analysis of single-thermalversus ICG-thermal EVLW.

Bias 7.0 ml kg-1 (±5.5), LOA ±10.5 ml kg-1

Data from all measurement points (n=40). Data presented as bias (±SD) and 95% limits of agreement (LOA). Dotted lines indicate bias and 95% LOA.

EVLW, extravascular lung water volume; Li-Thermal, lithium thermal double indicator dilution; ICG-thermal, indocyanine green-thermal double indicator dilution.

Supplementary Figure 3 Bland-Altman analysis of Li-thermaland single-thermal versus ICG-thermal measurement of ITBV.

Data from all measurement points (n=40). Data presented as bias (±SD) and 95% limits of agreement (LOA). Dotted lines indicate bias and 95% LOA. ITBV, intrathoracic blood volume; Li-thermal, lithium thermal double indicator dilution; ICG-thermal, indocyanine green-thermal double indicator dilution; Single thermal, single thermal indicator dilution