A review of the experimental evidence on the toxicokinetics of carbon monoxide: the potential role of pathophysiology among susceptible groups.

BACKGROUND

Acute high level carbon monoxide (CO) exposure can cause immediate cardio-respiratory arrest in anyone, but the effects of lower level exposures in susceptible persons are less well known. The percentage of CO-bound hemoglobin in blood (carboxyhemoglobin; COHb) is a marker of exposure and potential health outcomes. Indoor air quality guidelines developed by the World Health Organization and Health Canada, among others, are set so that CO exposure does not lead to COHb levels above 2.0%, a target based on experimental evidence on toxicodynamic relationships between COHb and cardiac performance among persons with cardiovascular disease (CVD). The guidelines do not consider the role of pathophysiological influences on toxicokinetic relationships. Physiological deficits that contribute to increased CO uptake, decreased CO elimination, and increased COHb formation can alter relationships between CO exposures and resulting COHb levels, and consequently, the severity of outcomes. Following three fatalities attributed to CO in a long-term care facility (LTCF), we queried whether pathologies other than CVD could alter CO-COHb relationships. Our primary objective was to inform susceptibility-specific modeling that accounts for physiological deficits that may alter CO-COHb relationships, ultimately to better inform CO management in LTCFs.

METHODS

We reviewed experimental studies investigating relationships between CO, COHb, and outcomes related to health or physiological outcomes among healthy persons, persons with CVD, and six additional physiologically susceptible groups considered relevant to LTCF residents: persons with chronic obstructive pulmonary disease (COPD), anemia, cerebrovascular disease (CBD), heart failure, multiple co-morbidities, and persons of older age (≥ 60 years).

RESULTS

We identified 54 studies published since 1946. Six studies investigated toxicokinetics among healthy persons, and the remaining investigated toxicodynamics, mainly among healthy persons and persons with CVD. We identified one study each of CO dynamics in persons with COPD, anemia and persons of older age, and no studies of persons with CBD, heart failure, or multiple co-morbidities. Considerable heterogeneity existed for exposure scenarios and outcomes investigated.

CONCLUSIONS

Limited experimental human evidence on the effects of physiological deficits relevant to CO kinetics exists to support indoor air CO guidelines. Both experimentation and modeling are needed to assess how physiological deficits influence the CO-COHb relationship, particularly at sub-acute exposures relevant to indoor environments. Such evidence would better inform indoor air quality guidelines and CO management in indoor settings where susceptible groups are housed.