Carbon monoxide inhalation poisoning

Abstract

Carbon monoxide (CO) inhalation is a relatively common cause of toxicity, often unnoticed due to non specific clinical
presentation. Central nervous system and heart are mainly involved
by mechanisms that come from the high affinity of hemo-proteins
for CO, leading to hypoxic and peroxidation damage. Diagnosis may
require a high grade of suspicion, oxygen supplemental therapy is
the main pillar of therapy but supportive measures may be needed,
as hemodynamic, respiratory and mental complications can occur.
Late neuropsychiatric disorders are possible, for which early hyperbaric oxygen treatment may be of benefit. Pneumon 2014, 27(1):21-24.

Full text

Nikolaos Chavouzis, MD, MSc
Ioannis Pneumatikos MD, PhD, FCCP
Department of Critical Care Medicine,
University Hospital of, Alexandroupoli Greece
Key words:
- Carbon monoxide (CO)
- Carboxyhemoglobin (COHB)
- Hyperbaric oxygen (HBO)
Correspondence
Ioannis Pneumatikos
Professor of Critical Care Medicine
Head, Department of Intensive Care Unit
University Hospital of Alexandroupolis
Tel.: +302551075081, Fax: +302551030423
E-mail: ipnevmat@med.duth.gr
Carbon monoxide inhalation poisoning
SUMMARY. Carbon monoxide (CO) inhalation is a relatively com-
mon cause of toxicity, often unnoticed due to non specific clinical
presentation. Central nervous system and heart are mainly involved
by mechanisms that come from the high affinity of hemo-proteins
for CO, leading to hypoxic and peroxidation damage. Diagnosis may
require a high grade of suspicion, oxygen supplemental therapy is
the main pillar of therapy but supportive measures may be needed,
as hemodynamic, respiratory and mental complications can occur.
Late neuropsychiatric disorders are possible, for which early hyper-
baric oxygen treatment may be of benefit. Pneumon 2014, 27(1):21-24.
INTRODUCTION
Carbon monoxide (CO) poisoning is the reason for up to 45.000 emer-
gencies per year in the US and is considered responsible for 5.000-6.000
deaths.
1
Fire incidents and combustion exhaust in inadequately venti-
lated spaces are the most common situations of serious CO intoxication
and death, while some lower level of exposure, leading to milder clinical
symptoms, usually is the result of increased atmospheric CO (heavy traffic
– industrialized urban environment, occupational exposure).2 CO poisoning
recently enjoys an unwelcome popularity in Greece during the economic
crisis, due to the increasing household use of combustion-based heaters
(sometimes even improvised), instead of central heating installments or
electricity-powered devices.
PATHOGENESIS
The mechanisms of action of CO intoxication involve the classical tis-
sue hypoxia and the, more recently discovered, direct cellular damage of
immunological and inflammatory etiology. The hypoxemic effect is the
result of hemoglobin’s (Hgb) approximately 210–fold higher affinity for CO,
compared to O2. Carbon monoxide lowers blood’s O2 capacity by displacing
it from Hgb to form carboxyhemoglobin (COHgb), but also induces an O2
dissociation curve left shift the of the unaffected oxyhemoglobin (O2Hgb),
thus decreasing further the ability of unloading O
2
to the tissues
3
(Figure 1).
This “relative anemia” reduces the oxygen delivery and could cause direct
Editorial

22 PNEUMON Number 1, Vol. 27, January - March 2014
hypoxic injury to sensitive organs (i.e., heart and brain).
Cellular toxicity from CO poisoning is directly associated
with its affinity for other heme-containing proteins, includ-
ing cytochromes, myoglobin and guanylyl cyclase.4 As CO
binds to cytochromes it compromises energy production
at mitochondrial level by free radical mediated mecha-
nisms.5 Myoglobin binding of CO inhibits the transport
of O2 to the mitochondria that may lead to myocardial
and skeletal muscle hypoxia, direct cellular necrosis and
rhabdomyolysis.
6
The CNS is affected by CO release at
neuronal level, which initiates glutamate over-release,
influx of calcium into the cells, free-radical-mediated in-
jury and additional neutrophil activation, with final result
lipid peroxidation, neuronal death and demyelination.7
CLINICAL PRESENTATION
Brain and myocardium are more sensitive to the ef-
fects of CO due to their higher metabolic and oxygen
demands. Despite the multiplicity of novel mechanisms
proposed to explain the damage made by CO, the direct
hypoxemic effect should not be overlooked, mainly in
cases of brain injury in subjects with underlying heart
and / or lung co-morbidities. Therefore, certain popula-
tions (i.e., coronary artery disease, chronic obstructive
pulmonary disease) are more vulnerable to the effects
of CO and could present symptoms of hypoxia and even
death at lower levels of COHgb than generally expected.
The symptoms associated with CO poisoning usually
begin with headache (>80%), and follow a climax, as the
concentration of COHgb rises, that includes dyspnea,
chest pain, nausea, vomiting, impaired judgment, visual
disturbances, fatigue, confusion, coma, seizures, circulatory
and respiratory failure and death. The main symptoms
come from the CNS, probably by the hypoxemic effect
that leads to increased intracranial pressure and cerebral
edema. Although symptoms generally follow the above
order in relation to COHgb levels, there is no clear cor-
relation, probably due to the influence of other factors,
like co-morbidities, age, duration of exposure and genetic
susceptibility.2
Besides the acute presentation, a delayed neuropsy-
chiatric syndrome may occur in patients, from 3 up to
240 days after the CO exposure. This happens grossly
in unpredicted manner, and although some risk factors
have been identified, there is no secure predictive crite-
rion, including the COHgb levels and the seriousness of
the acute event. Even those victims without immediate
neuropsychological symptoms may demonstrate delayed
impairment, ranging from subtle personality changes
or mild cognitive deficit to severe dementia, psychosis,
parkinsonism, incontinence. Behavioral impairments re-
ported include alterations in attention, executive function,
verbal fluency, motor abilities, visual-spatial skills, learning,
short-term memory and mood/social adjustment. The late
neuropsychiatric sequelae have been shown to occur in
up to 50% of the patients with >10% COHgb, they have
a mean onset latency of 3 weeks and, generally, have a
relatively good prognosis (50-70% remission in one year).
1
DIAGNOSIS
Carbon monoxide poisoning diagnosis is based on the
triad of: 1) recent history of a situation compatible with
CO exposure, 2) symptoms consistent of CO poisoning
and 3) laboratory finding of elevated COHgb level. There
FIGURE 1. The solid line depicts the normal dissociation curve,
the dashed line shows the impact of reducing the hemoglo-
bin content by half (anemia) and one (small dotted line) the
impact of 50% COHgb. The left shift associated with COHgb
demonstrates the extra adverse effect of CO versus merely
loss of hemoglobin O2 carrying capacity. The partial pressure
of O2 when hemoglobin gives up 50% of its available O2 is at
~16 mm Hg (Pv1O2) when COHgb is 50%, versus ~26 mm Hg
(Pv2O2) when there is a 50% anemia.

23PNEUMON Number 1, Vol. 27, January - March 2014
ing the oxygenation of a CO poisoned patient. First, when
interpreting the blood gas analysis, a physician should be
able to rule out if the oxygen saturation value reported is
a measured or a calculated one. Modern ABG machines
typically perform spectrophotometry on injected sample,
thus directly measuring the concentrations of oxy-, de-
oxy-, carboxy- and methemoglobin and they report the
corresponding values labeled as measured. Some older
models calculate oxygen saturation based upon algo-
rithms that use the dissociation curve and pH, reporting
a calculated Sat% value, irrespective of the real amount
of COHgb present on the sample. Second, standard two
wavelength (660 – 990 nm) pulse oxymeters cannot
differentiate oxy- and carboxyhemoglobin, because the
two molecules share similar wavelength absorbances.
No clinically important difference in the value reported
by an ordinary pulse oxymeter will be noted, unless
COHgb levels rise to more than 40%, which makes this
method unacceptable. Special CO pulse oxymeters are
available commercially since 2005 but substitution of
blood sampling with non invasive measurement is not
recommended for clinical decisions.8
MANAGEMENT
The first-line treatment in all cases of CO poisoning
is the administration of high fraction of inspired oxygen,
using a high-flow non-rebreathing mask, or by mechani-
cal ventilation when the endotracheal intubation criteria
are met.11 The eventuality of intubation and ICU transfer
should be assessed, if mental status suggests unprotected
upper airway or there is prominent hemodynamic and /
or respiratory compromise. Supplemental oxygen acceler-
ates the elimination of CO from the related hemoproteins
and alleviates tissue hypoxia. There are no clinical trials in
favor of this practice, although, it is reasonable to recom-
mend the administration of high-flow oxygen the sooner
possible, even as a pre-hospital care in case of suspected
CO poisoning, and until COHgb level normalizes (<3%)
and the symptoms are weaned, usually for 6 h.
The use of hyperbaric oxygen (HBO) is a valid alterna-
tive to normobaric 100% oxygen (NBO), but the relative
inconvenience, limited availability, high cost and logistical
problems, practically tend to limit its use. Several studies
have addressed the comparison between HBO and NBO,
there is no evidence that HBO influences the mortality
rate, but there are studies in favor of a better outcome
in terms of late cognitive sequelae up to one year after
treatment.8 Risk factors for long-term cognitive impair-
is no single symptom or a combination of symptoms that
may confirm or exclude the diagnosis, the most frequent
ones include headache, nausea, vomiting, confusion, fa-
tigue, chest pain, dyspnea, loss of consciousness. “Cherry
red” skin or mucous membranes coloring, caused by the
brighter shade of red that capillary COHgb has, compared
to O2Hgb, requires a lethal exposure to become evident
and therefore should rather be considered a necropsy
finding than a valid clinical sign.
8
Clinical suspicion should
be raised upon awareness of various, non strictly medical,
factors (eg. socioeconomical status, eventual suicide at-
tempt, occupation, seasonal incidence during cold days) as
well as frequently related medical situations, such as acute
coronary syndrome and arrhythmias. Clinical investigation
should include other eventual members of a household
that may be in risk of exposure. If the suspected source
of a CO poisoning victim is an occupational or residential
setting that may endanger public health, civil protection
services should be urgently notified.
Clinical diagnosis of CO poisoning should be con-
firmed by an elevated level of COHgb, either in arterial
or venous blood sample. Carboxyhemoglobin levels vary
with smoking habit, inhaled air concentration and dura-
tion of exposure, time gap from exposure termination
to blood sampling, supplemental O2 therapy before the
time of measurement. Normal value of COHgb for non
smokers is <2% and for smokers 3-12%. Smokers are
usually in the 3-5% range, can rarely exceed 10% and a
general rule of 2,5% increase for every pack / day may be
used.
8
Environmental air exposure levels considered safe
according to WHO range from 87 ppm (100 mg/m3) for 15
min, to 8,7 ppm (10 mg/m
3
) for 8 h, while exposure of any
duration to air containing more than 100 ppm is danger-
ous to human health.
9
The COHgb levels measured at the
time of clinical investigation must be interpreted with
respect to the half life of CO in blood. Normobaric O2 at
100% speeds up the displacement of CO from circulating
hemoglobin, reducing the T1/2 to approximately 75 min,
compared to 320 min when breathing room air10, and it
may be furthered lowered to 20 min using hyperbaric O2
(HBO
2
) treatment
2
. A poisoned patient with initial COHgb
concentration of 30% breathing normobaric 100% O
2
during a 2 h transportation to emergency department
could present a modest 10% or less of COHgb when
measured, therefore, obtaining a blood sample early,
possibly at the site of poisoning, could be of use when
CO poisoning is suspected.
A short comment is necessary regarding the confusion
that may arise from measuring COHgb levels and assess-

24 PNEUMON Number 1, Vol. 27, January - March 2014
ment in patients not treated with HBO are considered
age >36 years, exposure duration >24 h, loss of con-
sciousness and COHgb level >25%.12 It is recommended
to consider HBO within the first 24 h in patients with risk
factors, even if they are clinically stable and seem not
likely to die because of the CO poisoning.11 Hyperbaric
oxygen treatment is considered safe during pregnancy
and is recommended in pregnant women, irrespective
of poisoning severity. Optimum dose and frequency of
treatment are unknown, in practice these decisions are
left to the attending hyperbaric physician, usually patients
are treated at 3 atm for up to 3 treatments, if they remain
symptomatic.13
If the CO exposure is suspected to be an attempted
suicide, toxicology exams should be made to screen for
eventual use of drugs, chemicals or alcohol. Impaired
mental status that is not explained by the CO expo-
sure and / or insists after several hours of supplemental
oxygen treatment is highly indicative of co-poisoning.14
Severe metabolic acidosis (pH <7,20 or plasma lactate
>10 mmol/L) is positively correlated with high short-term
mortality (30-50%) and, in these cases, concomitant cya-
nide poisoning is likely, especially when the CO source
is a fire incident. Empiric treatment with the antidote
hydroxycobalamin is recommended.15
Patients with heart disorders are more likely to pres-
ent features of cardiac ischemia, such as angina, infarc-
tion, conduction abnormalities and sudden death. Car-
diologic evaluation and monitoring, including work up
for myocardial ischemia should be offered to selected
patients.
2
All patients surviving a CO poisoning should
be scheduled at least one follow up visit 1-2 months
after the event to screen for late cognitive impairments.
Memory disturbance, depression, anxiety, inability to
calculate and motor dysfunction rarely may develop,
but studies suggest that mortality rate after an episode
of CO poisoning is higher compared with the normal
population, fact that may be explained by accidental
deaths due to these symptoms. Patients with evidence
of cardiac damage should be scheduled for cardiology
follow-up and patients with intended exposure should
have mandatory psychiatric care.8
PREVENTION
It is thought that public education programs designed
to increase awareness of CO poisoning and placement of
warning labels on commercially used fuels and devices
emitting CO could have some effect in reducing the in-
cidence. It should be noted that many of the candidate
victims may not be native speakers, so warning signs
instead of verbal notes could be more effective. The install-
ment and use of CO alarms in residential or occupational
closed spaces could be a valid preventive measure.
REFERENCES
1. Huzar TF, George T, Cross JM. Carbon monoxide and cyanide
toxicity: etiology, pathophysiology and treatment in inhalation
injury. Expert Rev Respir Med 2013; 7:159-170.
2. Prockop LD, Chichkova RI. Carbon monoxide intoxication: an
updated review. J Neurol Sci 2007; 262:122-130.
3. Roughton FJW, Darling RC. The effect of carbon monoxide on
oxyhemoglobin dissociation curve. Am J Physiol 1944; 141:17-31.
4.
Kao LW, Nanagas KA. Toxicity associated with carbon monoxide.
Clin Lab Med 2006; 26:99-125.
5.
Hardy KR, Thom SR. Pathophysiology and treatment of carbon
monoxide poisoning. J Toxicol Clin Toxicol 1994; 32:613-629.
6.
Finely J, VanBeck A, Glover JL. Myonecrosis complicating carbon
monoxide poisoning. J. Trauma 1977;17:536-540.
7.
Thom SR. Dehydrogenase conversion to oxidase and lipid
peroxidation in brain after carbon monoxide poisoning. J Appl
Physiol 1992; 73:1584-1589.
8.
Hampson NB, Piantadosi CA, Thom SR, Weaver LK. Practice
recommendations in the diagnosis, management, and preven-
tion of carbon monoxide poisoning. Am J Respir Crit Care Med
2012; 186:1095-1101.
9.
Department of the Enviroment. Expert panel on air quality
standard. London: HMSO; 1994.
10. Weaver LK, Howe S, Hopkins RO, Chan K. Carboxyhemoglobin
half-life in carbon monoxide poisoned patients treated with
100% oxygen at atmospheric pressure. Chest 2000; 117:801-808.
11.
Weaver LK. Clinical practice: carbon monoxide poisoning. N
Eng J Med 2009; 369:1217-1225.
12.
Weaver LK, Valentine KJ, Hopkins RO. Carbon monoxide poison-
ing: risk factors for cognitive sequelae and the role of hyperbaric
oxygen. Am J Respir Crit Care Med 2007; 176:491-497.
13. Hampson NB, Mathieu D, Piantadosi CA, Thom SR, Weaver L.
Carbon monoxide poisoning: Interpretation of randomized
clinical trials and unresolved treatment issues. Undersea Hyperb
Med 2001; 28:157-164.
14. Hampson NB, Bodwin D. Frequency of toxic co-ingestions in
intentional carbon monoxide poisoning. J Emerg Med 2013;
44:625-630.
15.
Lawson-Smith P, Jansen EC, Hyldegaard O. Cyanide intoxication
as part of smoke inhalation: a review on diagnosis and treat-
ment from the emergency perspective. Scand J Traum Resusc
Emerg Med 2011; 19:14.