Affiliations: Osaka University Graduate School of Medicine
Salt Lake City, UT
Correspondence to: Takeshi Shimazu, MD, Department of Traumatology and Acute Critical Medicine (D-8), Osaka University Graduate School of Medicine, 2–15 Yamadaoka, Suita-shi, Osaka, 565-0871 Japan; e-mail: email@example.com
To the Editor:
I read with interest the article by Weaver et al (March
2000)1on the half-life of blood carboxyhemoglobin (COHb)
in carbon monoxide poisoning patients because we also have analyzed the
elimination process of carbon monoxide in clinical and experimental
settings.2 They retrospectively analyzed 93 patients with
carbon monoxide poisoning and calculated the half-life of COHb based on
single exponential decrease which is described as Ct = C0*
e(− kt), where C0 and Ct are COHb
concentrations at time 0 and at any time, respectively, and k is the
decay constant. They also hypothesized that the COHb half-life of
carbon monoxide-poisoned patients will be longer than that of human
volunteers breathing carbon monoxide under experimental protocol partly
because of greater carbon monoxide burden in patients with carbon
monoxide accumulation in tissue as well as onto hemoglobin. However, I
am afraid there were a couple of misunderstandings and confusion
regarding the physiologic nature of the carbon monoxide absorption and
elimination process, which can be described precisely using physiologic
First, the carbon monoxide elimination process exhibits biphasic
decreases of COHb concentration compatible with a two-compartment
model: an initial rapid decrease (distribution phase), followed by a
slower phase (elimination phase).2 In other words, COHb
elimination should be described by the sum of two exponentials rather
than a commonly accepted single exponential decrease. Such biphasic
shape is more prominent when the duration of exposure to carbon
monoxide is short because of distribution of carbon monoxide from
hemoglobin (COHb) to tissues as well as elimination from the lung.
However, as the half-life of the initial phase is short, it might not
always be clearly noticeable if the peak COHb is low and/or if the
blood samples were not taken early enough. The authors commented that
there were no differences in the COHb half-life calculated using all
COHb measurements compared to the half-life calculated by using either
the first and second or the first and last COHb measurements in the
same patients. The biphasic decrease can still be observed in
carbon monoxide-poisoned patients if measurement of COHb is made more
closely from earlier time (Fig 1
Secondly, the authors did not consider the fact that the half-life of
COHb is affected significantly by the duration of exposure to carbon
monoxide, which determines what they call carbon monoxide burden in
tissues and hemoglobin. It is only after approximately 5 to 6 h
that the blood COHb concentration reaches a plateau after exposure to
carbon monoxide (Fig 2
). So if the exposure time is less than several hours, carbon monoxide
distribution in the body does not reach equilibrium and the elimination
process would not follow the single exponential decay. The apparent
discrepancy between reported COHb half-lives could be explained by
considering the duration of exposure. For example, Peterson and
Stewart3exposed their subjects to 500 parts per million
of carbon monoxide for 2.3 h, yielding the peak COHb of 25%,
while Pace et al4 studied the half-life after the
volunteers rebreathed a mixture of 250 mL of carbon monoxide and 2 L of
air (approximately 11% carbon monoxide) from a rubber bag for 30
s, causing peak COHb of 4%. So it is a matter of course that the
half-life obtained by Pace et al4 is much shorter than
that by Peterson and Stewart.3
The half-life of COHb is affected indeed by various factors, such as
duration of carbon monoxide exposure, time for transport, fraction of
inspired oxygen during transport, minute ventilation,
Pao2, etc, but there is no mystery
that would cause unexplainable differences of COHb half-life between
and within experimental and clinical studies.
We appreciate Dr. Shimazu’s comments regarding our observations
of carboxyhemoglobin half-life (COHb t½) in a series of
patients that were poisoned with carbon monoxide.1Dr.
Shimazu points out that carbon monoxide elimination exhibits a biphasic
decrease of carboxyhemoglobin (COHb) concentration compatible with a
two-compartment model, where there is an initial rapid decrease
(distribution phase) followed by a slower phase (elimination phase).
Dr. Shimazu refers to his own work,2 in which he and his
colleagues measured absorption and elimination of carbon monoxide in
four sheep (short-duration carbon monoxide exposure) in an experimental
protocol. However, the authors provided no information to support the
finding that carbon monoxide absorption and elimination by sheep is
identical to that in humans. Information regarding similarities or
differences between humans and sheep is important in order to draw
inferences and compare it to that of a retrospective
study,1 in which data from 93 carbon monoxide-poisoned
patients treated with oxygen were analyzed. As stated in our
article,1 we inspected the COHb t½
calculated using all COHb measurements compared to the COHb
t½ calculated by using either the first and second, or
the first and last COHb measurements in the same patients and found no
difference in the COHb t½.
Alternatively, it is possible that Dr. Shimazu’s observations from
sheep experiments do extrapolate to humans. In the few patients in
which we had multiple COHb measurements, if the initial COHb
measurement occurred relatively late in the course of COHb elimination,
it is possible that an early rapid fall in COHb may have been missed.
The data from the patient with carbon monoxide poisoning provided by
Dr. Shimazu in Figure 1 may suggest a biphasic COHb t½,
but other explanations of the biphasic appearance of this curve are
possible. The explanations include changes in the patient’s alveolar
ventilation, alterations in gas exchange efficiency, or variability in
cardiac output during the time of the COHb measurements. All of these
factors influence COHb t½, as we noted in our
article.1 Only if all of the above-mentioned factors are
controlled during the time of the COHb measurements, could one conclude
that the COHb t½ of this patient was biphasic.
The second point of Dr. Shimazu is that we did not consider that carbon
monoxide elimination may be affected by the duration of exposure to
carbon monoxide. As we stated in our article,1 our study
was retrospective and in many of the carbon monoxide-poisoned patients
it was impossible to determine the duration of their carbon monoxide
exposure. We accept that the COHb t½ may be affected by
the duration and dose of carbon monoxide exposure. However, in clinical
carbon monoxide poisoning, it is unknown if the duration or dose of
carbon monoxide exposure affects the COHb t½.
Dr. Shimazu appears to have missed the major contribution of our
article.1 Dr. Shimazu states, “ . . . there is no
mystery that would cause unexplainable differences of COHb half-life
between and within experimental and clinical studies.” One of the
main findings of our study is that the COHb t½ of
clinically carbon monoxide-poisoned patients is different than the COHb
t½ measured in humans under controlled experimental
conditions. A second finding of our study is to show that age, gender,
smoking, smoke inhalation, loss of consciousness, initial COHb, or a
metabolic acidosis did not affect the COHb t½.
We appreciate Dr. Shimazu’s interest in our work and his comments and
observations, which are important to further understanding of carbon
monoxide absorption and elimination.
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