http://www.cinda.org/support/articles/MCS-CMP.html
BMJ 1999;319:1082-1083 ( 23 October )
Editorials
Carbon monoxide poisoning
Is still an underrecognised problem The onset of autumn and cooler weather
traditionally heralds the start of another season in the northern hemisphere
the peak incidence of unintentional deaths from carbon monoxide. Each year
around 50 people in the United Kingdom die from carbon monoxide poisoning, and
a year ago the chief medical officer warned again of the dangers.1 As yet there
is no evidence that the population is at any lesser risk.
Humans have been poisoned by carbon monoxide since they first discovered
hydrocarbon fuels, incomplete combustion of which is the usual cause of
poisoning. Napoleon's surgeon, Larrey, saw soldiers with carbon monoxide
induced myonecrosis
when billeted in huts heated by woodburning stoves. And over 60 years ago
American
physicians were warned that chronic carbon monoxide exposure could mimic many
neurological conditions, such as "cerebral haemorrhage, encephalitis, multiple
sclerosis, spastic paraplegia, chorea and tetany."2 Throughout the world people
continue to die unnecessarily from carbon monoxide exposure or to survive their
encounter with disabling symptoms whose cause is misdiagnosed.
Carbon monoxide famously binds to haemoglobin over 200 times more strongly than
oxygen, a strange evolutionary quirk explained by the tiny amounts of carbon
monoxide produced naturally in the body by haem oxygenase and the need to have
an efficient scavenging system for such a toxic substance.3 Although the
carboxyhaemoglobin which results from inhaling the gas is an indicator of
exposure, clinical features may persist or begin long after the disappearance
of measurable carboxyhaemoglobin, which has a half life of only four to five
hours when clean air is breathed. Displacement of oxygen
from haemoglobin is merely the best known property of carbon monoxide, which
poisons the body in many more subtle and complex ways.
Carbon monoxide interferes with other ferroproteins such as myoglobin and
various enzymes including members of the cytochrome family.4 Studies suggest
that endogenous carbon monoxide may share properties with nitric oxide, such as
smooth muscle relaxation and altered platelet aggregation, and be intimately
linked with nitric oxide dependent reactions, which if unregulated can lead to
cellular death. Oxidative damage to neurovascularepithelium produced by carbon
monoxide causes increased leucocyte adherence and subsequent peroxidation of
brain lipid. 5 6
The central nervous system is thus especially vulnerable, with areas at
arterial "watersheds" such as the medulla and basal gangliaat particular risk.1
The damage can be shown radiologically.7 Isolated neurological symptoms such as
gesture apraxia and single seizures have been ascribed to carbon monoxide
poisoning, as has "winter headache." A delayed neurological syndrome,8 which
may mimic almost any neuropsychiatric complaint, though impaired motor control
is usually a prominent feature, has been reported up to 80 days after carbon
monoxide exposure. Yet this syndrome is both preventable and treatable if the
true cause is recognised.9
Economics and geography, as much as pathology and biochemistry, determine
someone's susceptibility to carbon monoxide poisoning. Korea's population is
slightly smaller the United Kingdom's, yet 20 years ago there were around 3000
deaths and a million admissions a year,10 and by 1982, 300 hospitals were
equipped with hyperbaric oxygen facilities. Korean houses are still commonly
heated by a large coal brick dropped into a space beneath the living area.
Horizontal "chimneys" pass under other rooms in the house to provide heat, and
several dwellings often share a final common flue.
In Chesterfield recently a family of four and their elderly neighbour died
because the common chimney to their housesbuilt of porous material became
blocked, venting fumes from a gas boiler into both homes.11 All five deaths
would almost certainly have been prevented by a domestic carbon monoxide alarm.
More modern house design brings its own problems, however. In a well insulated
home the negative pressure created by a bathroom extractor fan can be enough to
cause retrograde flow in an otherwise normal chimney. Most people think of
engine exhaust as a means of deliberate self poisoning, but in Quebec it is the
commonest cause of unintentional carbon monoxide deaths, when engines are left
running in enclosed spaces, for warmth or when being repaired.
Numbers of cases sublethal exposure to carbon monoxide in Britain are
traditionally quoted as 200 a year, but up 250,000 gas appliances are condemned
annually. Even assuming that as few as 10% of these appliances were giving off
significant amounts of carbon monoxide, and discounting exposure from other
domestic sources, this suggests that as many as 25 000 people every year may be
exposed to the effects of carbon monoxide within the home. Whatever the actual
number, the overwhelming majority of cases go unrecognised, unreported, and
untreated. Chronic carbon monoxide exposure is
misdiagnosed. A survey carried out by the charity Carbon Monoxide Support
showed that in only one case out of 77 was exposure correctly identified on the
basis of symptoms alone.12
The early symptoms of carbon monoxide poisoning are usually said to be flu
like, which, though arguably true, also encourages the wrong diagnosis. As a
result a doctor's most likely response when faced with more than one member of
a household exhibiting similar symptoms is to think of a vague microbial cause
(a diagnosis never tested) when in reality a far more prosaic cause may exist.
Symptoms may initially be mild, often include gastrointestinal upset more in
children, and usually bear a temporal relation to occupancy of a particular
building or room. Classically, several family members (including pets) are
affected. Testing for carboxyhaemoglobin is straightforward and will pick up
exposure in its early stages. Oximetry on a sample of blood has long been the
only useful immediate
investigation, but breath meters, originally developed as smoking cessation
aids, are now available.13 Most of the time no one thinks to do the test.
Perhaps the most tragic consequence of a missed diagnosis is that patients may
be discharged to the very environment that is poisoning them. When deaths are
investigated it is not uncommon to find that the victim sometimes even several
members of the same family had visited a doctor with symptoms of carbon
monoxide toxicity in the days before death. With a simple, non-invasive testing
device the chances of such tragedies could be dramatically lessened. But to
achieve this we must also see increased awareness of the problem, among both
patients and their doctors.
Ed Walker, staff grade practitioner.
Accident and Emergency Department, Dewsbury District Hospital, Dewsbury WF13
4HS
([email hidden])
Alastair Hay, reader in chemical pathology.
Molecular Epidemiology Unit, University of Leeds LS2 9JT
Acknowledgments
We acknowledge the help of Debbie Davis at Carbon Monoxide Support.
1.
Department of Health. Letter from the Chief Medical Officer. London: DoH, 1998
(PL/CMO/98/5).
http://www.doh.gov.uk/cmo/cmo98_5.htm
2.
Beck H. Slow carbon monoxide asphyxiation: a neglected clinical problem. JAMA
1936; 17: 1025-1028.
3.
Torrance RW. Haldane and indifferent gases: O2 secretion or CO excretion.
Respir Physiol 1996; 106:
109-113[Medline].
4.
Miro O, Casademont J, Barrientos A, Urbano-Marquez A, Cardellach F.
Mitochondrial cytochrome c oxidase
inhibition during acute carbon monoxide poisoning. Pharmacol Toxicol 1998; 82:
199-202[Medline].
5.
Thom SR. Leukocytes in carbon monoxide-mediated brain oxidative injury.
Toxicol Appl Pharmacol 1993; 123:
234-237[Medline].
6.
Ischiropoulos H, Beers MF, Ohnishi ST, Fisher D, Garner SE, Thom SR. Nitric
oxide production and perivascular
tyrosine nitration in brain following carbon monoxide poisoning in the rat. J
Clin Invest 1996; 97:
2260-2267[Abstract/Full Text].
7.
Tom T, Abedon S, Clark RI, Wong W. Neuroimaging characteristics in carbon
monoxide toxicity. J Neuroimaging
1996; 6: 161-166[Medline].
8.
Plum F, Posner JB, Hain RF. Delayed neurological deterioration after anoxia.
Arch Intern Med 1962; 110: 18-25.
9.
Thom SR, Taber R, Mendiguren I, Clark J, Hardy K, Fisher A. Delayed
Neuropsychologic sequelae after carbon
monoxide poisoning: prevention by treatment with hyperbaric oxygen. Ann Emerg
Med 1995; 25: 535-537[Medline].
10.
Song DB. Epidemiology of carbon monoxide poisoning in Korea. J Korean Med
Assoc 1985; 28: 1059-1063.
11.
Wainwright M. UK news. Guardian 1999; 22 Feb:5.
12.
Carbon Monoxide Support. The effects of chronic exposure to CO. Leeds: Carbon
Monoxide Support, 1997.
13.
Wallace W. The use of exhaled carbon monoxide for the diagnosis of carbon
monoxide poisoning; a case report. Alaska
Med 1998;40: Apr-Jun:33-5.
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And see the associated article too.
http://www.bmj.com/cgi/content/full/319/7217/1083
BMJ 1999;319:1083-1084 ( 23 October )
Editorials
Hyperbaric oxygen in carbon monoxide poisoning.
Conflicting evidence that it works
There is little dispute that carbon monoxide poisoning is common: in the United
States
it produces an estimated 40 000 emergency department visits each year,1 and the
accompanying editorial outlines the difficulties in diagnosing poisoning caused
by this "silent killer" There is disagreement, however, about how best to treat
carbon monoxide poisoning, and in particular about the role of hyperbaric
oxygen.
Carbon monoxide is produced endogenously in small amounts and as a byproduct of
incomplete combustion. It is colourless, odourless, and undetectable by human
senses. It binds to haemoglobin, displacing oxygen; causes a leftward shift of
the oxyhaemoglobin dissociation curve; binds to many intracellular proteins;
and may interfere with ATP production at the cytochrome level.2 It can also
activate neutrophils pathologically, leading to a reperfusion injury manifested
by lipid peroxidation.3 Low levels of carbon monoxide produce evidence of
oxidative stress.4
Recently, apoptosis in brain tissue has been observed after carbon monoxide
poisoning.5
Supplemental oxygen was found helpful in treating carbon monoxide poisoning in
1868,6 and hyperbaric oxygen was first used for clinical poisoning in 1942.7
The theoretica benefits of hyperbaric oxygen include a faster reduction in
carboxyhaemoglobin levels, increased intracellular delivery of oxygen, and
reduced neutrophil activation and adherence, thereby reducing lipid
peroxidation.8
Despite anecdotal reports on the beneficial effects of hyperbaric oxygen for
acute carbon monoxide poisoning,8 its role in such poisoning has been
questioned. 9 10 Four randomised clinical trials have studied the issue in
humans. Raphael et al treated non-comatose acutely poisoned patients with
hyperbaric or normobaric oxygen and found no difference in subjective outcome
at one month.11
In a small trial in conscious patients Ducasse observed that hyperbaric oxygen
preserved vascular responsiveness to acetazolamide and that treated patients
had better quantitative electroencephalograms than those treated with
normobaric oxygen.12 Thom et al randomised conscious poisoned patients to
hyperbaric or normobaric oxygen and found no delayed neurological sequelae in
those receiving hyperbaric oxygen.13 Only limited inferences can be drawn from
these trials, however, because of methodological problems, including lack of
blinding,11-13 possible ineffective hyperbaric oxygen dosing,11 delays in
giving hyperbaric oxygen,11 inconsistent and incomplete follow up, 11 13 lack
of functional (neuropsychological) outcome measures, 11 12 and failure to
enroll unconscious patients.11-13
A recent Australian double blind randomised trial addresses some of these
limitations.10 Scheinkestel et al showed that hyperbaric oxygen did not improve
cognitive outcome in acute carbon monoxide poisoning, including in severe
poisoning; indeed, they found that it might worsen outcome, in that more of the
severely poisoned patients in the hyperbaric oxygen group had a poor outcome at
completion of treatment. Most of their 191 patients (73%) had severe poisoning
and most had attempted suicide (76%).
Concomitant depression and use of psychoactive drugs might have influenced the
results. The delay before most patients received hyperbaric oxygen (about seven
hours) might have reduced its effectiveness.8 Scheinkestel et al used high
concentrations of oxygen continuously in both groups for three days, and more
in patients who remained abnormal at three days. This dose of normobaric oxygen
is generally not used in carbon monoxide poisoning, so the controls might not
have represent a true control group for testing whether hyperbaric oxygen
improves or worsens outcome. Cluster
randomisation was necessary for practical purposes, but this might have caused
differences between the two arms of the trial. All patients were admitted to
hospital, and Scheinkestel et al's report would have been strengthened if it
had included detailed outcome information at hospital discharge. Also the study
is weakened by the fact that one month follow up was low (46%).
Nevertheless, this study reminds us of how damaging carbon monoxide poisoning
can be: hospital mortality was 3%, and neuropsychological sequelae were present
in 71% of patients at hospital discharge, and 62% at one month. Even with
hyperbaric oxygen, neuropsychological sequelae occur,14 and without hyperbaric
oxygen, including in severe carbon monoxide poisoning, a normal functional
recovery is possible.15 Unfortunately, no
marker exists that will predict which patients will develop neurocognitive
sequelae. In carbon monoxide poisoning treatment of many of the pathological
processes that occur is probably time dependent, and if patients are not
treated promptly with hyperbaric oxygen one can reason that hyperbaric oxygen
might be ineffective. However, the time window for
hyperbaric oxygen in human carbon monoxide poisoning is unknown.
Thom has shown in rats that lipid peroxidation can be prevented if hyperbaric
oxygen is
used within 90 minutes of carbon monoxide exposure.16 Obviously, prevention of
carbon monoxide poisoning remains paramount. Households with attached garages
or with any flame source should have regular inspections of their furnaces as
well as carbon monoxide alarms. Those people who do suffer acute carbon
monoxide poisoning deserve, at the minimum, several hours of high
concentrations of oxygen (preferably
100% oxygen) and follow up after the poisoning. And if cognitive and affective
problems are detected after carbon monoxide poisoning these patients should be
referred to neuropsychologists and occasionally psychiatrists. However,
although both 100% normobaric oxygen and hyperbaric oxygen are accepted
treatments for carbon monoxide poisoning, it remains unclear on present
evidence whether hyperbaric oxygen offers a substantial advantage in clinical
poisoning.
For now clinicians must balance the costs and risks of transport of hyperbaric
treatment against its theoretical benefits. We still need a well designed,
multicentre, prospective, randomised controlled trial to answer the question of
when, if at all, to refer patients with acute carbon monoxide poisoning
..
Lindell K Weaver, medical director, hyperbaric medicine.
LDS Hospital, University of Utah School of Medicine, Salt Lake City, Utah
84143,
USA
Acknowledgments
The carbon monoxide research conducted by LKW's department has been funded by
the
Deseret Foundation, LDS Hospital,
and he has received honorariums to speak on carbon monoxide poisoning. 1.
Hampson NB. Emergency department visits for carbon monoxide poisoning in the
pacific northwest. J Emerg Med
1998; 16: 695-698[Medline].
2.
Piantadosi CA. Toxicity of carbon monoxide: hemoglobin vs histotoxic
mechanisms. In: Penney DG, ed. Carbon
monoxide. Boca Raton: CRC Press, 1996:163-186.
3.
Thom SR. Carbon monoxide mediated brain lipid peroxidation in the rat. J Appl
Physiol 1990; 68: 997-1003[Medline].
4.
Thom SR, Ischiropoulos H. Mechanism of oxidative stress from low levels of
carbon monoxide. Health Effects
Institute 1997; 80: 1-19[Medline].
5.
Piantadosi CA, Zhang J, Levin ED, Folz RJ, Schmechel DE. Apoptosis and delayed
neuronal damage after carbon
monoxide poisoning in the rat. Exp Neurol 1997; 147: 103-104[Medline].
6.
Linas AJ. [Meeting of July 17, 1868.] Bulletins et Memoires de la Societe de
Therapeutique. 1868; 2: 32-37.
7.
End E, Long CW. Oxygen under pressure in carbon monoxide poisoning. J Ind Hyg
Toxicol 1942; 24: 302-306.
8.
Carbon monoxide poisoning. In: Hampson NB, chairman. Hyperbaric oxygen
therapy: a committee report. Bethesda,
Maryland: Undersea and Hyperbaric Medical Society, 1999:9-12.
9.
Tibbles PM, Perrotta PL. Treatment of carbon monoxide poisoning: a critical
review of human outcome studies
comparing normobaric oxygen with hyperbaric oxygen. Ann Emerg Med 1994; 24:
269-276[Medline].
10.
Scheinkestel CD, Bailey M, Myles PS, Jones K, Cooper DJ, Millar IL, et al.
Hyperbaric or normobaric oxygen for
acute carbon monoxide poisoning: a randomized controlled clinical trial. Med J
Australia 1999; 170:
203-210[Medline].
11.
Raphael JD, Elkharrat D, Jars-Guincestre MC. Trial of normobaric and
hyperbaric oxygen for acute carbon monoxide
intoxication. Lancet 1989; 2: 414-419[Medline].
12.
Ducasse JL, Celsis P, Marc-Vergnes JP. Non-comatose patients with acute carbon
monoxide poisoning: hyperbaric or
normobaric oxygenation? Undersea Hyperbaric Med 1995; 22: 9-15[Medline].
13.
Thom SR, Taber RL, Mendiguren II, Clark JM, Hardy KR, Fisher AB. Delayed
neurologic sequelae after carbon
monoxide poisoning: Prevention by treatment with hyperbaric oxygen. Ann Emerg
Med 1995; 24: 474-480.
14.
Weaver LK. Carbon monoxide poisoning. In: Guntupalli KK, Hanania NA, eds.
Environmental emergencies. Critical
care clinics. Philadelphia: Saunders, 1999:297-317.
15.
Weaver LK, Hopkins RO, Larson-Lohr V. Neuropsychologic and functional recovery
from severe carbon monoxide
poisoning without hyperbaric oxygen therapy. Ann Emerg Med 1996; 27:
736-740[Medline].
16.
Thom SR. Antagonism of carbon monoxide-mediated brain lipid peroxidation by
hyperbaric oxygen. Toxicol Appl
Physiol 1990; 105: 340-344.