Clarifications Regarding Interference of Hydroxocobalamin With Carboxyhemoglobin Measurements in Victims of Smoke Inhalation
2007; Elsevier BV; Volume: 50; Issue: 5 Linguagem: Inglês
10.1016/j.annemergmed.2007.05.026
ISSN1097-6760
Autores Tópico(s)Neonatal Health and Biochemistry
ResumoI read with great interest the study done by Lee et al regarding interferences of hydroxocobalamin with co-oxymeter measurements.1Lee J. Mukai D. Kreuter D. et al.Potential interference by hydroxocobalamin on cooximetry hemoglobin measurements during cyanide and smoke inhalation treatments.Ann Emerg Med. 2007; 49: 802-805Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Co-oxymeters are highly valuable tools that have improved the frequency of diagnosis of carbon monoxide poisonings.2Duenas-Laita A. Ruiz-Mambrilla M. Gandia F. et al.Epidemiology of acute carbon monoxide poisoning in a Spanish region.J Toxicol Clin Toxicol. 2001; 39: 53-57Crossref PubMed Scopus (42) Google Scholar However, co-oxymetry cannot be considered as a reference method for determination of carboxyhemoglobin.2Duenas-Laita A. Ruiz-Mambrilla M. Gandia F. et al.Epidemiology of acute carbon monoxide poisoning in a Spanish region.J Toxicol Clin Toxicol. 2001; 39: 53-57Crossref PubMed Scopus (42) Google Scholar, 3Allred E.N. Bleecker E.R. Chaitman B.R. et al.Effects of carbon monoxide on myocardial ischemia.Environ Health Perspect. 1991; 91: 89-132Crossref PubMed Scopus (66) Google Scholar A number of interferences have been reported, including lipid-induced turbidity, hyperbilirubinemia, sulfhemoglobin, fetal hemoglobin, and methylene blue.4Gouget B. Gourlain H. Présentation des caractéristiques des CO-oxymètres.Revue Européenne de Technologie Biomédicale. 1995; 17: 243-246Google Scholar The interferences are dependent on the method of measurement, precluding generalization of the results.4Gouget B. Gourlain H. Présentation des caractéristiques des CO-oxymètres.Revue Européenne de Technologie Biomédicale. 1995; 17: 243-246Google ScholarThe authors limited their study to interference with hydroxocobalamin. However, hydroxocobalamin will be immediately transformed into cyanocobalamin. In the future, studies aimed at determining interferences of cobalamins must include not only those caused by hydroxocobalamin but also those caused by cyanocobalamin.The authors spiked 5 ml blood sample with 12 mg hydroxocobalamin to obtain hydroxocobalamin concentrations of 1.784, 0.892, and 0.382 mM in whole blood. However, hydroxocobalamin is measured in plasma. Therefore, assuming a hematocrit of 50%, the addition of 12 mg of hydroxocobalamin to whole blood would result in plasma concentrations 2-fold greater than those expected. Data about plasma hydroxocobalamin concentrations in humans suggest that maximal measured concentrations are about 600 μmol/l (range: 267-1011 μmol/l,5Forsyth J.C. Mueller P.D. Becker C.E. et al.Hydroxocobalamin as a cyanide antidote: safety, efficacy and pharmacokinetics in heavily smoking normal volunteers.J Toxicol Clin Toxicol. 1993; 31: 277-294Crossref PubMed Scopus (116) Google Scholar far less than the range studied by Lee et al.1Lee J. Mukai D. Kreuter D. et al.Potential interference by hydroxocobalamin on cooximetry hemoglobin measurements during cyanide and smoke inhalation treatments.Ann Emerg Med. 2007; 49: 802-805Abstract Full Text Full Text PDF PubMed Scopus (40) Google ScholarThe use of normal carboxyhemoglobin to assess the interferences of hydroxocobalamin is questionable. Co-oxymeters are not sufficiently sensitive for very low carboxyhemoglobin levels.6Gourlain H. Buneaux F. Levillain P. Mesure du CO et de la COHb dans le sang: interférences de l'hydroxocobalamine et du bleu de méthylène en CO-oxymétrie.Revue Française des Laboratoires. 1996; 282: 144-148Crossref Scopus (5) Google Scholar Gourlain et al has shown the interference of hydroxocobalamin with carboxyhemoglobin. They concluded that the interference of hydroxocobalamin with co-oxymeter measurement, while being moderate, should be taken into account. While being statistically significant, the differences are neither of clinical relevancy nor misleading. Indeed, the presence of hydroxocobalamin consistently resulted in slight overestimation of carboxyhemoglobin. The major concern in carbon monoxide poisoning is underdiagnosis rather than mild overestimation. Carboxyhemoglobin may be used to consider hyperbaric oxygen. Values of interest are about 15% and 25%. Assuming the same percentage of interference, the false values would be 15.9% and 26.6%, respectively. It is rather unlikely that such limited interferences would significantly impair the indications of the attending physician. In clinical practice, the 2 major pitfalls we have to face when dealing with the analytical assessment of carbon monoxide poisoning are: 1) any delay in blood sampling, especially if the patient is treated with oxygen, and 2) significant delays between collection of blood and measurement using co-oxymeters.6Gourlain H. Buneaux F. Levillain P. Mesure du CO et de la COHb dans le sang: interférences de l'hydroxocobalamine et du bleu de méthylène en CO-oxymétrie.Revue Française des Laboratoires. 1996; 282: 144-148Crossref Scopus (5) Google Scholar These biases would have a far greater impact on carboxyhemoglobin measurement than the transient presence of high plasma hydroxocobalamin concentrations.In cases of suspected carbon monoxide poisoning, emergency care providers are advised to collect a blood specimen as soon as possible. Smoke inhalation is a setting where carbon monoxide exposure is highly likely. Consequently, emergency care providers should collect a blood specimen on anticoagulant for carboxyhemoglobin measurement while inserting a venous line and before hydroxocobalamin administration in fire victims suspected of smoke-induced cyanide poisoning. I read with great interest the study done by Lee et al regarding interferences of hydroxocobalamin with co-oxymeter measurements.1Lee J. Mukai D. Kreuter D. et al.Potential interference by hydroxocobalamin on cooximetry hemoglobin measurements during cyanide and smoke inhalation treatments.Ann Emerg Med. 2007; 49: 802-805Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Co-oxymeters are highly valuable tools that have improved the frequency of diagnosis of carbon monoxide poisonings.2Duenas-Laita A. Ruiz-Mambrilla M. Gandia F. et al.Epidemiology of acute carbon monoxide poisoning in a Spanish region.J Toxicol Clin Toxicol. 2001; 39: 53-57Crossref PubMed Scopus (42) Google Scholar However, co-oxymetry cannot be considered as a reference method for determination of carboxyhemoglobin.2Duenas-Laita A. Ruiz-Mambrilla M. Gandia F. et al.Epidemiology of acute carbon monoxide poisoning in a Spanish region.J Toxicol Clin Toxicol. 2001; 39: 53-57Crossref PubMed Scopus (42) Google Scholar, 3Allred E.N. Bleecker E.R. Chaitman B.R. et al.Effects of carbon monoxide on myocardial ischemia.Environ Health Perspect. 1991; 91: 89-132Crossref PubMed Scopus (66) Google Scholar A number of interferences have been reported, including lipid-induced turbidity, hyperbilirubinemia, sulfhemoglobin, fetal hemoglobin, and methylene blue.4Gouget B. Gourlain H. Présentation des caractéristiques des CO-oxymètres.Revue Européenne de Technologie Biomédicale. 1995; 17: 243-246Google Scholar The interferences are dependent on the method of measurement, precluding generalization of the results.4Gouget B. Gourlain H. Présentation des caractéristiques des CO-oxymètres.Revue Européenne de Technologie Biomédicale. 1995; 17: 243-246Google Scholar The authors limited their study to interference with hydroxocobalamin. However, hydroxocobalamin will be immediately transformed into cyanocobalamin. In the future, studies aimed at determining interferences of cobalamins must include not only those caused by hydroxocobalamin but also those caused by cyanocobalamin. The authors spiked 5 ml blood sample with 12 mg hydroxocobalamin to obtain hydroxocobalamin concentrations of 1.784, 0.892, and 0.382 mM in whole blood. However, hydroxocobalamin is measured in plasma. Therefore, assuming a hematocrit of 50%, the addition of 12 mg of hydroxocobalamin to whole blood would result in plasma concentrations 2-fold greater than those expected. Data about plasma hydroxocobalamin concentrations in humans suggest that maximal measured concentrations are about 600 μmol/l (range: 267-1011 μmol/l,5Forsyth J.C. Mueller P.D. Becker C.E. et al.Hydroxocobalamin as a cyanide antidote: safety, efficacy and pharmacokinetics in heavily smoking normal volunteers.J Toxicol Clin Toxicol. 1993; 31: 277-294Crossref PubMed Scopus (116) Google Scholar far less than the range studied by Lee et al.1Lee J. Mukai D. Kreuter D. et al.Potential interference by hydroxocobalamin on cooximetry hemoglobin measurements during cyanide and smoke inhalation treatments.Ann Emerg Med. 2007; 49: 802-805Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar The use of normal carboxyhemoglobin to assess the interferences of hydroxocobalamin is questionable. Co-oxymeters are not sufficiently sensitive for very low carboxyhemoglobin levels.6Gourlain H. Buneaux F. Levillain P. Mesure du CO et de la COHb dans le sang: interférences de l'hydroxocobalamine et du bleu de méthylène en CO-oxymétrie.Revue Française des Laboratoires. 1996; 282: 144-148Crossref Scopus (5) Google Scholar Gourlain et al has shown the interference of hydroxocobalamin with carboxyhemoglobin. They concluded that the interference of hydroxocobalamin with co-oxymeter measurement, while being moderate, should be taken into account. While being statistically significant, the differences are neither of clinical relevancy nor misleading. Indeed, the presence of hydroxocobalamin consistently resulted in slight overestimation of carboxyhemoglobin. The major concern in carbon monoxide poisoning is underdiagnosis rather than mild overestimation. Carboxyhemoglobin may be used to consider hyperbaric oxygen. Values of interest are about 15% and 25%. Assuming the same percentage of interference, the false values would be 15.9% and 26.6%, respectively. It is rather unlikely that such limited interferences would significantly impair the indications of the attending physician. In clinical practice, the 2 major pitfalls we have to face when dealing with the analytical assessment of carbon monoxide poisoning are: 1) any delay in blood sampling, especially if the patient is treated with oxygen, and 2) significant delays between collection of blood and measurement using co-oxymeters.6Gourlain H. Buneaux F. Levillain P. Mesure du CO et de la COHb dans le sang: interférences de l'hydroxocobalamine et du bleu de méthylène en CO-oxymétrie.Revue Française des Laboratoires. 1996; 282: 144-148Crossref Scopus (5) Google Scholar These biases would have a far greater impact on carboxyhemoglobin measurement than the transient presence of high plasma hydroxocobalamin concentrations. In cases of suspected carbon monoxide poisoning, emergency care providers are advised to collect a blood specimen as soon as possible. Smoke inhalation is a setting where carbon monoxide exposure is highly likely. Consequently, emergency care providers should collect a blood specimen on anticoagulant for carboxyhemoglobin measurement while inserting a venous line and before hydroxocobalamin administration in fire victims suspected of smoke-induced cyanide poisoning. In reply:Annals of Emergency MedicineVol. 50Issue 5PreviewWe agree that the magnitude of the potential interference in CO hemoglobin level readings caused by hydroxocobalamin is likely to be small and not be clinically significant under normal circumstances. The degree of interference should not limit clinical use of the cyanide antidote hydroxocobalamin in suspected or confirmed cyanide poisoning, or alter decisionmaking with regard to patient management and we do not want to overestate the possible clinical impact. However, co-oximetry and reporting of CO hemoglobin is relatively routine and rapid in many hospitals, particularly burn centers where this situation might be expected to be encountered. Full-Text PDF
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