Distributions of Ventilation-Perfusion Ratios in Acute Respiratory Failure

Analysis of V/Q-matching—a safety “biomarker” in pulmonary drug development?

“…As tracer gases, oxygen, carbon dioxide, or nitrogen can serve (Hope et al, 1995;de Gray et al, 1997). The most advanced method to determine V/Qratios is the multiple inert gas elimination technique (MIGET; Wagner et al, 1974), which employs six tracer gases with different blood solubility. A saline solution equilibrated with the tracer gases is infused and arterial and alveolar gas concentrations are measured.…”

“…This does not hold true for severe forms of V/Q-mismatch (e.g. in ARDS) where arterial oxygen levels can remain low despite mechanical ventilation with 100% inspired oxygen (Wagner et al, 1974(Wagner et al, , 1977West, 1995).…”

“…Similar findings could be observed in ARDS (Cornet et al, 2010), in ILD (Augusti, 1994, and especially with different vasoactive interventions (Barberá and Blanco, 2009). The degree of VQM and its relation is not equal in all conditions: for example, while being prominent in ARDS (Wagner et al, 1974) and COPD (Augusti, 1994), in ILD; on the other hand, it was less clear and vasodilator effects on VQM in ILD are less prevalent (Günther et al, 2007).…”

“…As pointed out above despite its relevance for oxygen delivery to the organism the measurement of V′/Q′-mismatch is not trivial and the current gold standard method MIGET (Wagner et al, 1974(Wagner et al, , 1977, which has provided a better understanding of the V′/Q′-physiology, is only used in a few centers worldwide and certainly could not serve as a biomarker in large clinical trials.…”

“…This gas-exchange impairment leads to a decrease in arterial oxygen partial pressure (paO 2 ), arterial oxygen saturation of hemoglobin (SaO 2 ; hypoxemia) with decreased tissue O 2 delivery. In patients with pneumonia, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), VQM is most relevant for the respective degree of impaired gas exchange and resulting hypoxemia (Figure 2; Wagner et al, 1974Wagner et al, , 1977West, 1995West, , 1996Preston, 2007;Tunnicliffe and Shah, 2008;Blanco et al, 2010;Cornet et al, 2010).These lung diseases have in common that in certain regions of the lung Q′ will be higher compared with V′ (V′/Q′ < 1) because…”