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Expired carbon monoxide as a marker of CO poisoning and its application in determining treatment End-points

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Smart, DR (2005) Expired carbon monoxide as a marker of CO poisoning and its application in determining treatment End-points. PhD thesis, University of Tasmania.

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Abstract

Carbon monoxide (CO) is a colourless, odourless toxic gas that is able to substitute for oxygen at
many levels in the oxygen cascade. CO poisoning is responsible for nearly a quarter of suicide deaths
in Australia, and hundreds of individuals sustain non-fatal poisoning every year. Up to two thirds of
individuals who survive CO poisoning have long-term neurological or cognitive impairment. Despite
years of study by medical researchers, a reliable marker of acute CO poisoning severity that correlates
with outcome has not been identified. Oxygen is known to be an antidote to CO poisoning, yet there is
significant debate regarding the dose required, and the treatment duration. The end-point of CO
excretion from the body is the lungs. Measurement of expired CO has been documented since the
1980’s, however there has been limited study of ECO in poisoned patients.
In this research ECO was investigated as marker of CO poisoning, and its application in determining
treatment end-point. A low cost, portable and non-invasive apparatus was successfully developed for
measurement of ECO, oxygen concentration and minute volume. The apparatus was then evaluated in
a variety of settings, for adults and children, and to establish baseline ranges for non-smokers, smokers
and poisoned individuals, breathing air, NBO and HBO. The technique of measuring ECO was further
investigated to determine the relationship between ECO and COHb, and for the diagnosis of CO
poisoning. The apparatus was evaluated in the clinical setting to determine pulmonary CO elimination
kinetics. A prospective series of CO poisoned patients was enrolled to determine if acute ECO levels
correlated with clinical outcomes and to assess whether unrecordable ECO was a suitable marker of
treatment end-point. In this research, expired oxygen concentration was also monitored, to ensure that
all individuals received the stated dose of oxygen. Baseline levels of ECO were found to be very low in healthy non-smoking volunteers, and in nonsmoking
divers treated for decompression illness, consistent with the observation that most CO derives
from exogenous sources. Smokers had higher baseline ECO than non-smokers, and smoker ECO
levels correlated positively with the number of cigarettes smoked per day, and negatively with the time
since last cigarette.
Breathing air and NBO, a strong positive linear relationship between the ECO and COHb was
observed for non-poisoned smokers, poisoned individuals and pooled data. Expired CO concentration
increased in proportion with increasing FIO2 for 0.21 (air) to 1.0 (NBO). While breathing 100% oxygen, increasing ambient pressure from 1 ATA to 2.8ATA did not alter the ECO concentration (ppm) in each breath.
However, elimination of CO was greatly enhanced due to the increased density of gas at higher pressures. Each tidal
volume at 2.8ATA actually contains 2.8 times as many molecules of CO compared with the same tidal volume at
1ATA ambient pressure. When poisoned subjects breathed NBO and HBO, significant amounts of ECO
were detectable when the COHb was unrecordable using the biochemical method. This suggested that
ECO more accurately reflected remaining CO in body stores than COHb, however this might have
resulted from the limits of the biochemical method for detecting low levels of COHb (< 2%).
Concurrent measurement of expired oxygen provided useful confirmation that the intended 100%
oxygen dose was delivered to all treated individuals.
ECO was a useful non-invasive test to diagnose acute (< 6 hours) CO poisoning, when ECO values
were > 40 ppm. For ECO values of 7 ppm to 40 ppm, clinical information would be needed to separate
mildly poisoned individuals from smokers. Expired CO and COHb were equally effective in
identifying acutely poisoned individuals, from smokers and non-smokers. Critical values of ECO >40
ppm or COHb > 7% were shown to be highly specific for CO poisoning.
Expired CO demonstrated single stage exponential elimination kinetics in both NBO and HBO
treatment environments. CO elimination in HBO was significantly faster than NBO. There was a seven
to ten-fold variation in CO elimination between individuals in either treatment (NBO or HBO). Based
on these findings, current empirical regimens may over-treat some individuals and under-treat others.
The half-lives determined for ECO elimination were longer than those determined for COHb. This
suggests that elimination of CO via the breath may be slower than elimination from Hb. If
unrecordable ECO proved useful as a treatment endpoint, this would allow treatment to be tailored to
the individual’s acute CO load. In the clinical series of 66 acutely poisoned patients, there were a high number of males sustaining CO
poisoning from deliberate self-harm. These individuals had longer exposures, greater neurological
toxicity, and were more likely to have LOC than accidental exposures. The greater toxic effect and
higher CO body load was most likely due to breathing leaded petrol exhaust containing high CO levels
to attempt suicide. In keeping with their greater neurological toxicity, there was a positive correlation
between ECO, COHb levels, and the severity of poisoning. The ECO measurement breathing oxygen
correlated significantly with the severity of neurological impairment in the ED. This provided support
for ECO levels as useful guide to acute clinical poisoning severity. However, acute ECO and COHb levels measured in the ED were not predictive of outcome at 3 months. This may have been affected
by significant delays in transferring patients for HBO treatment.
Just over 28% of patients had poor outcomes at 3 months, using unrecordable ECO as a treatment endpoint.
At this point, patients who had abnormal neurological or cognitive function remained abnormal
at 3 months. Unfortunately the treatment endpoint using ECO did not prevent cases of DNS, or the
need to provide follow-up for CO poisoned patients. The occurrence of DNS after all CO had been
removed suggests that DNS may result from mechanisms other than direct CO toxicity.
Poor outcomes were associated with delays to study entry, suicide attempts, motor vehicle exhaust as a
source of CO and acidosis measured in the ED. Individuals with LOC did not have a significantly
worse outcome than those remaining conscious during their CO exposure. HBO and NBO treated
patients had similar levels of PNS, however the HBO group had a lower incidence of DNS – an
unexpected finding. Because the study was not randomized, it was not possible to conclude this is a
definite treatment effect. Compared with NBO, HBO treatment led to faster removal of CO, and
shorter treatments.
Measurement of ECO constitutes a novel non-invasive method of monitoring of acute CO poisoning. It
has potential to compliment existing methods of monitoring acute CO poisoning, and may be useful as
a non-invasive test to diagnose CO poisoning. Clinical outcomes in this series compared favourably
with other series of similar severity poisoning in the literature. However, further research using a
randomized controlled trial is required to determine if unrecordable ECO is a useful guide to treatment
endpoint.

Item Type: Thesis (PhD)
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Date Deposited: 24 Mar 2013 22:24
Last Modified: 15 Sep 2017 01:06
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