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Is the Coburn-Forster-Kane Prediction Equation Valid at Low or Spiking Levels of Carbon Monoxide or Under Conditions of Rapid Changes in Ventilation?

HISTORY OF VALIDATION OF THE COBURN-FORSTER-KANE EQUATION

The Coburn-Forster-Kane (CFK) equation accurately predicted increases in blood carboxyhemoglobin (COHb) in resting male subjects during carbon monoxide (CO) exposures (constant 8.5 to 1,000 parts per million [ppm]; Peterson and Stewart 1975), during 60-second (sec) exposures to high CO concentrations (Tikuisis et al. 1987a), and during exercise in subjects breathing a constant CO concentration (Tikuisis et al. 1992) (see Appendix B). Tikuisis et al. (1987b) compared measured venous COHb and computed COHb using the CFK equation under conditions in which inspired CO was changed by evoking transient changes in inspired CO concentrations of 500-2,000 ppm and over times as short as 60 sec. Because of slow lung wash-in after CO was added to inspired air and wash-out after CO was discontinued, alveolar CO concentrations were constantly changing, but no sudden changes were studied. Computed COHb, obtained by using a “normalized” alveolar CO concentration that was obtained by integration, closely followed measured values. These investigators also showed that, in subjects exercising at constant different workloads during CO uptake for times as short as 60 sec, measured increases in venous COHb could be precisely computed using the CFK equation. In general, the above studies used inspired CO concentrations in excess of those found in the cabin air of armored vehicles.

NEED FOR VALIDATION OF THE CFK EQUATION UNDER CONDITIONS FOUND IN ARMORED-VEHICLE CABIN AIR

The committee was provided with several examples of CO concentration profiles representing the inside of armored-vehicle cabins during the test firing scenarios. These few examples show spikes in CO concentration lasting several seconds after weapons had been fired. Following multiple firings, there are gradual increases in inter-spike CO concentrations, followed by similarly gradual decreases in CO concentration after firing ceases due to ventilation of cabin air. The small number of examples provided to the committee illustrates considerable variability in CO concentration tracings, where spikes following firings were 25-2,500 ppm and interspike CO concentrations reached 100-500 ppm. These few examples are not necessarily representative of all scenarios, as CO concentrations within the cabin can vary depending on opened or closed hatches, operating ventilation fans, wind conditions, or armored-vehicle movements, as well as the history of weapons firings (M. Bazar, CHPPM, personal commun., September 23, 2008). Although it is established that the CFK equation can be used to predict blood COHb after 60- to 75-sec constant CO exposures or during slow changes in inspired CO concentrations, there are no data in



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3 Is the Coburn-Forster-Kane Prediction Equation Valid at Low or Spiking Levels of Carbon Monoxide or Under Conditions of Rapid Changes in Ventilation? HISTORY OF VALIDATION OF THE COBURN-FORSTER-KANE EQUATION The Coburn-Forster-Kane (CFK) equation accurately predicted increases in blood carboxyhemo- globin (COHb) in resting male subjects during carbon monoxide (CO) exposures (constant 8.5 to 1,000 parts per million [ppm]; Peterson and Stewart 1975), during 60-second (sec) exposures to high CO con- centrations (Tikuisis et al. 1987a), and during exercise in subjects breathing a constant CO concentration (Tikuisis et al. 1992) (see Appendix B). Tikuisis et al. (1987b) compared measured venous COHb and computed COHb using the CFK equation under conditions in which inspired CO was changed by evoking transient changes in inspired CO concentrations of 500-2,000 ppm and over times as short as 60 sec. Be- cause of slow lung wash-in after CO was added to inspired air and wash-out after CO was discontinued, alveolar CO concentrations were constantly changing, but no sudden changes were studied. Computed COHb, obtained by using a “normalized” alveolar CO concentration that was obtained by integration, closely followed measured values. These investigators also showed that, in subjects exercising at constant different workloads during CO uptake for times as short as 60 sec, measured increases in venous COHb could be precisely computed using the CFK equation. In general, the above studies used inspired CO con- centrations in excess of those found in the cabin air of armored vehicles. NEED FOR VALIDATION OF THE CFK EQUATION UNDER CONDITIONS FOUND IN ARMORED-VEHICLE CABIN AIR The committee was provided with several examples of CO concentration profiles representing the inside of armored-vehicle cabins during the test firing scenarios. These few examples show spikes in CO concentration lasting several seconds after weapons had been fired. Following multiple firings, there are gradual increases in inter-spike CO concentrations, followed by similarly gradual decreases in CO con- centration after firing ceases due to ventilation of cabin air. The small number of examples provided to the committee illustrates considerable variability in CO concentration tracings, where spikes following firings were 25-2,500 ppm and interspike CO concentrations reached 100-500 ppm. These few examples are not necessarily representative of all scenarios, as CO concentrations within the cabin can vary depend- ing on opened or closed hatches, operating ventilation fans, wind conditions, or armored-vehicle move- ments, as well as the history of weapons firings (M. Bazar, CHPPM, personal commun., September 23, 2008). Although it is established that the CFK equation can be used to predict blood COHb after 60- to 75-sec constant CO exposures or during slow changes in inspired CO concentrations, there are no data in 14

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CGK Equation at Low or Spiking CO or Under Rapid Changes in Ventilation the literature from experiments that replicate the rapid changes in CO concentrations measured in ar- mored-vehicle cabins, that is, CO spikes of a few seconds durations. There are also no results reported in the literature from experiments that replicate changes in pulmonary ventilation found in armored-vehicle personnel. Two issues need to be addressed: • Do the high CO concentrations found during spikes influence CO uptake, and how can these data be used to obtain a relevant “normalized” inspired CO to plug into the CFK equation? • Do increases in workload and ventilation in armored-vehicle personnel augment CO uptake? Previous studies used inspired CO concentrations in excess of those found in armored-vehicle cabins, and data need to be obtained using lower CO concentrations. The committee recommends that the Army conduct three types of experiments using human sub- jects to address those issues. Details on methods for each experiment are provided in Appendix C. • Experiment 1. Effects of rapid changes in inspired CO concentration at a constant rate of ven- tilation. This experiment will have one part that addresses the relationship of inspired CO concentrations to CO uptake. The other part will evaluate the CFK equation. • Experiment 2. Effects of rapid changes in ventilation at a constant inspired CO concentration. • Experiment 3. Effects of simultaneous increases in inspired CO concentration and ventilation on CO uptake, venous blood COHb, and COHb predicted by the CFK equation. The CFK equation could be evaluated by using animals, such as dogs or cats. However, there are numerous practical arguments against substituting animal data for human data: (1) animal testing would require anesthesia, and the animals could not exercise; (2) animal testing would require development of new approaches. Because experimenters would probably not have previous information in the diffusion capacity and other pertinent variables, they would need to be measured; (3) whereas equipment for con- ducting experiments using human subjects is already present in pulmonary-function laboratories, such equipment would need to be developed and/or procured for a comparable animal study; (4) the study of effects of increases in ventilation could be performed using animals but would be associated with de- creases in arterial oxygen tension and increases in blood pH, which could complicate findings; (5) the results from animal experiments would not be as relevant to the Army’s questions as would results ob- tained using human subjects; and (6) unlike the case for humans, there is no database from previous ani- mal studies to which to relate results. 15