MD (Res)There is evidence to suggest that therapy targeted at normalising extravascular lung water
volume (EVLW) can improve outcomes from critical illness. Indocyanine green-thermal
double indicator dilution (ICG-thermal) is considered the clinical reference standard of
EVLW volume measurement but is no longer commercially available. The accuracy and
reliability of the only clinically available technology (single-thermal indicator dilution) has
been questioned in several studies. This thesis incorporates two clinical studies and one
laboratory study designed to assess the measurement of EVLW and intrathoracic blood
volumes using a prototype lithium-thermal double indicator dilution technique.
The proof of concept study suggested our hypothesis that intrathoracic blood volume
(ITBV), which is required for the calculation of EVLW volume, could be determined using
lithium indicator dilution, was valid. Peri-operative trends and absolute values of ITBV
were consistent with those obtained using ICG-thermal in a similar patient study group.
The median absolute value of ITBV measured at baseline using indocyanine green (1417
[±208] ml) was similar to that obtained using lithium indicator dilution 1542 (±601) ml.
EVLW volume measured by three indicator dilution techniques was then compared to postmortem
gravimetry in porcine models of acute lung injury. Sepsis and acute lung injury
were associated with increased EVLW volume, (9.2 [±3.0] ml kg-1), compared to sham
operated animals (6.6 [±0.45] ml kg-1) in keeping with previous studies. The Li-thermal
(Bias-1.8 [±13.1] ml kg-1) and ICG-thermal (Bias-1.0 [±6.6] ml kg-1) techniques
demonstrated acceptable accuracy, but wide limits of agreement suggested poor reliability.
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The single-thermal technique systematically over-estimated EVLW, with unacceptably
wide limits of agreement (Bias +8.5 [±14.5] ml kg-1). In this laboratory investigation, the
double indicator methods appeared more reliable than the single-thermal technique.
However none could be considered ideal.
Results of the final clinical study suggested EVLW volume measurement in man with the
Li-thermal method was clearly erroneous (Bias -7.6 [±7.4] ml kg-1) and compared poorly to
simultaneous measurements made using the ICG-thermal method (Bias +13.2 [±14.4] ml
kg-1). A considerable over-estimation of mean transit time (MTT) when compared to the
ICG-thermal technique (Bias 12.8 [±13] sec) was observed, a likely consequence of using
an external lithium ion electrode instead of an intra-arterial catheter. Manual analysis of the
dilution curves suggested considerable variability when compared to the automated
analysis. The poor accuracy of MTT, and consequently ITBV measurements in the clinical
study, may partly be due to software analysis of the lithium dilution curves. Thoracic blood
volumes derived from measurement of ICG transit time are reliable. However, EVLW
calculations based on the thermal indicator transit time are likely to be inaccurate.
The findings of these clinical and laboratory investigations demonstrate poor agreement
between both the prototype Li-thermal and the single thermal measurements of EVLW
volume and the ICG-thermal method. Trans-pulmonary lithium indicator dilution
measurements of ITBV and EVLW volume using an external lithium ion electrode are not
sufficiently accurate to safely guide clinical interventions in individual patients.
Consequently we decided not to further develop the lithium-thermal technique of EVLW
volume measurement
