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What are the limitations of methods to measure carbon monoxide in biological samples?

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Abstract

Purpose

Carbon monoxide (CO) is one of the most important toxic gases in the atmosphere. Its high affinity for hemoglobin has made carboxyhemoglobin (COHb) the most appropriate biomarker for CO poisoning. COHb is measured using spectrophotometric (ultraviolet-spectrophotometry, CO-oximetry) or gas chromatographic (GC) methods combined with flame ionization or mass spectrometry (MS) detectors. However, inconsistencies in many cases have been reported between measured values and reported symptoms, raising doubts as to the suitability of COHb as a biomarker and the accuracy and reliability of its measurement methods. Therefore, we aimed to review the accuracy of current methods used to measure CO and to determine their sources of error and their effects on the interpretation process.

Methods

A detailed search of PubMed was performed in November 2018 using relevant keywords. After exclusion criteria were applied, 46 articles out of 191 initial hits were carefully reviewed.

Results

While optical methods are highly influenced by changes in blood quality due to degradation of samples during storage, GC methods are less affected. However, measurement of COHb does not quantify free CO, which is mainly responsible for toxicity mechanisms other than hypoxia, such as inhibition of hemoproteins, thus underestimating the true CO burden. Therefore, measurement of COHb is not sufficiently accurate for diagnosis of CO poisoning.

Conclusions

An alternative biomarker is needed, such as determining the total amount of CO in blood. Although further research is required, we recommend that toxicologists consider all sources of error that can alter COHb concentrations, and in more challenging cases, they should use GC–MS methods to confirm the results obtained by spectrophotometry.

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Acknowledgements

The authors are grateful to Dr Ariana Zeka from Brunel University London for providing assistance in reviewing the manuscript and Dr Giovanni Leonardi from Public Health England for fruitful discussion on the topic as part of a collaborative project on carbon monoxide measurement error. This research received funding from the Gas Safety Trust, a UK-based grant-giving charity, grant number 2015-GST-01.

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  1. Forensic Toxicology and Chemistry Unit, University Centre of Legal Medicine Lausanne-Geneva, Chemin de la Vulliette 4, 1000, Lausanne, Switzerland

    Stefania Oliverio

  2. Department of Environmental Sciences, College of Health and Life Sciences, Brunel University London, London, UK

    Stefania Oliverio

  3. Swiss Human Institute of Forensic Taphonomy, University Center of Legal Medicine Lausanne-Geneva, Lausanne, Switzerland

    Vincent Varlet

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Oliverio, S., Varlet, V. What are the limitations of methods to measure carbon monoxide in biological samples?. Forensic Toxicol 38, 1–14 (2020). https://doi.org/10.1007/s11419-019-00490-1

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