Carboxyhemoglobin Tracks Acute Arterial Desaturation in Healthy Volunteers: a Pooled Analysis of Four Controlled Desaturation Studies

Acute arterial hypoxemia frequently occurs in perioperative and critical care settings; however, the dynamic changes in endogenous biomarkers under these conditions remain poorly characterized. This study aimed to identify which among carboxyhemoglobin (COHb), methemoglobin (MetHb), and lactate best tracks the severity of acute arterial desaturation, and to explore potential ethnic differences in their responses. Data were retrospectively analyzed from four controlled desaturation studies involving 48 healthy volunteers (32 Korean and 16 African). Participants inhaled a hypoxic gas mixture of air and nitrogen to maintain arterial oxygen saturation (SaO₂) between 70% and 100%. Arterial blood samples were collected at each target SaO₂ level to measure COHb, MetHb, and lactate concentrations using CO-oximetry. Linear mixed-effects models (LMMs) were used to quantify the association between SaO₂ and each biomarker while accounting for repeated measurements. A total of 1,194 arterial samples from 48 participants were analyzed. Across SaO₂ ranges of 70-80%, 80-90%, and 90-100%, COHb exhibited the largest relative change among the three biomarkers (P < 0.001). LMM analysis showed a significant association between decreasing SaO₂ and increasing COHb (β₁=-0.0123, P < 0.001). In contrast, no significant associations were observed for MetHb (β₁=0.0003, P = 0.677) or lactate (β₁=-0.0011, P = 0.175). In subgroup analyses, Korean participants demonstrated significantly greater COHb elevations than African participants with increasing severity of arterial desaturation (P < 0.001). Among the evaluated endogenous biomarkers, COHb most closely tracked the severity of acute arterial desaturation. The greater COHb response observed in Korean participants is hypothesis-generating and suggests possible ethnic variability in physiological responses to controlled arterial desaturation.Clinical trial registration: Clinical Research Information Service (CRIS), Republic of Korea (http://cris.nih.go.kr) KCT0008376, KCT0008746, KCT0009938, and KCT0010039.