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Carbon Treatment BY

ROY

Monoxide

Encephalopathy:

GINSBURG,

M.D..

AND

JOHN

Need

ROMANO,

ofa

OBSERVATION

ide poisoning neurological

patient

with

drew our attention to the and psychiatric symptoms

carbon

monox-

great variety of in this disorder

and to the lack of clarity concerning and treatment. This paper describes ofa patient with carbon monoxide

its clinical the clinical encephalopathy,

views

from

and

some

of the

major

suggests

some

new

CASE

the

course course re-

literature,

to treatment.

a 59-year-old

depressed

in June

housewife of 1973

of Italian

and

tried

extraction,

to commit

sui-

When this work

was done the authors were with the Department of Strong Memorial Hospital, University of Rochester School of Medicine and Dentistry, Rochester, N.Y. , where Dr. Ginsburg was Associate Resident and U.S. Public Health Service Psychiatry,

Fellow

in Psychiatry,

and Dr. Romano

is currently

Distinguished

University Professor of Psychiatry. Dr. Ginsburg is now a Grant Foundation Fellow in Psychopharmacology, Department of Psychiatry and Behavioral Science, Stanford University, Palo Alto, Calif. Address reprint requests to Dr. Romano at the Department of Psychiatry, University of Rochester, Rochester, N.Y. 14620. The authors would like to thank Drs. Robert and John Strauss for reviewing the manuscript.

Joynt,

Lowell

cide

by car

tered

nurse

exhaust

Lapham,

inhalation.

investigated

A neighbor

within

an hour

who

was

and found

a regis-

the patient

cyanotic and unresponsive. She was taken to the nearest hospital emergency room, where she was stuporous but not cornatose, and was not “cherry red.” Neurological examination was unremarkable, and a carboxyhernoglobin level was not obtained. An EEG and brain scan were within normal limits.

There was no history of neurological or psychiatric illness. After admission the patient became more alert but appeared depressed and could not concentrate. She was given three electroconvulsive treatments within a week. At first the patient seemed less depressed, but then she became increasingly

veloped

confused

and

stereotyped

withdrawn,

picking

refused

movements.

to eat,

Three

and

more

treatments were given 3 weeks after admission, patient’s confusion increased. Because of the unclear ofher illness, she was transferred to Strong Memorial tal for further evaluation.

A physical cooperative

examination patient

on admission

with

intermittent

revealed posturing.

de-

ECT

but the nature Hospi-

a mute, She

un-

respond-

ed with body movements to some commands but would not open her eyes or talk. The only positive physical or neurological finding was a bizarre gait; the patient would place and make small shuffling movements with while moving her body in a clockwise rotation.

Laboratory

REPORT

The patient, became

findings

approaches

Appropriate

M.D.

The authors describe severe psychiatric and neurological sequelae in a patient who suffered carbon monoxide poisoning as a result ofa suicide attempt. A review ofthe literature revealed that 15 to 40% of survivors ofcarbon monoxide poisoning develop neuropsychiatric symptoms, oftenfollowing a period ofapparent recovery. The authors advocate an aggressive treatment approach to carbon monoxide poisoning, emphasize the diagnostic value of extensive laboratory testing, and suggest that 2 to 4 weeks ofbedrest may prevent delayed neuropsychiatric sequelae.

RECENT

for

tests

revealed

that

the

patient’s

stand in her feet

hematocrit

was 35% and the hemoglobin revealed beta-thalassemia. Electrolyte levels, calcium, phosphorous, blood urea nitrogen, serum glutamic oxalacetic transaminase, lactic dehydrogenase, alkaline phosphatase, creatinine, total protein, albumin, glucose, uric acid, urinalysis, serology for syphilis,

T-4 by Murphy

Pattee,

within

limits.

opening

normal

and

fluid protein

closing

during

The patient

scan,

pressures

and glucose

Electroencephalogram since to the present rhythmic three-cycle

present

brain

A lumbar

levels

and

skull

X-rays

puncture

and

no cells;

were

within

spent

second

activity

most of her 4 months

all

normal

cerebrospinal

normal

on admission and repeated revealed persistent symmetrical

per drowsiness.

were

revealed

which

five

limits. times mono-

was

in the hospital

only

on

the floor, sitting, rocking, and staring blankly. She occasionally responded by giving her name in a faint whisper but otherwise would not talk to the nurses or her physicians. She often defecated in bed, and was sometimes physically aggres-

Am

J Psychiatry

133:3,

March

1976

317

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sive.

An interview

with

that the patient that she could

intravenous

behavior as being like ‘ ‘something first amytal interview, the patient ing staff, dress herself, and come

However, in bed. frequent

amytal

work

revealed

out of a book. ‘ ‘ After the was able to talk to the nursto the dining room to eat.

by the next morning she was again mute and lying For a period of 3 months the patient was given amytal interviews and these were, with some ex-

ceptions, fluoperazine

the

only and

tried without

times then

she would chlorpromazine

talk.

Treatment in high

with tndoses was

effect and then discontinued.

After 4 months transferred to the

term

sodium

was oriented for time, place, and person, and talk about her depression and of her bizarre

care.

Since

without Rochester

then

improvement, Psychiatric

the patient’s

the patient Center for

clinical

course

was long-

has not

changed significantly. She has generally remained mute, but when she does speak she confabulates. It became clear to the staff that she had considerable difficulty remembering recent events. Repeated neurological examination revealed bilateral tendon hyperreflexia, mask-like facies, and a parkinsonia

gait.

LITERATURE

REVIEW

The toxic been known containing

effects of carbon monoxide (CO) for centuries. In the past, household CO

was

the

dental and suicidal of natural gas and posune

has

principal

ingestion. electrical

diminished.

source

have gas

of both

acci-

With the increasing use heating this type of ex-

However,

the

development

of

(10),

carbon

However,

have

sociation

curve

to the

signs

10-30%

of patients

I to 3 weeks

after

ex-

oxygen from the hemoglobin the oxygen-hemoglobin disleft,

thus

increasing

the

binding

The

toris

(18).

the of

318

Am

tissues

(8).

J Psychiatry

133:3,

Marc/i

1976

die

per

mentation (8). usually fatal to a working man produces light Children, who

more

rapidly

than

of focal

and

general

neurological

first

competence, may acidosis, and angina

neurological

symptom

also pec-

to appear

is

fluctuating

symptoms

psychotic

depression

becomes

from

in-

CO

mimic

of

hys-

on

6, 12, 20). In particular the rapid changing of apraxias, agnosias, astasia-abasia, and the amnesticconfabulatory state often contributes to a false diag(5,

nosis of hysteria. It is also reasonable to assume that “hysterical” defense mechanisms may be used by patients who realize that they are damaged. Weinstein and Kahn (21) have described many patients with se-

illness

who

used

rather

bizarre

denial

mechanisms

rather than face the overwhelming task of confronting their disability. Recovery rates of those patients who do not relapse vary from several days to as long as 8 months (5). As would be expected, the highest cerebral functions relast.

Delayed ide

Patients nc

neurological

poisoning

often

examinations

between

to the

range

The

Often those tenia

the

of neurological signs has not been clinically (1, 6, 9) or in experimental

as 50 parts

of oxygen before the headache usually abolishes the pain (19).

tal or ciates patients within ties in

supply

between

frontal headache (19). The headache is often a delayed phenomenon; thus, lethal concentrations of CO may not produce any warning symptoms. Prompt adminis-

on arterial oxygen tension (P02). For example, a carboxyhemoglobin concentration of 9% may be equivalent to a 30% reduction of hemoglobin or a 46% reduction of arterial P02 (7). This shift substantially decreases tension

rate,

the degree of cardiovascular have hypotension, metabolic

nal exposure

oxygen

correlation

as low

respiratory

entire

nificance centration

The development correlated, either

be a gross

to level.

and psychiatric syndromes has been reproduced by carbon monoxide (2, 5, 6, 9, 12-17). The “cherry red” colon traditionally associated with CO poisoning is actually uncommon; in one series it was found in only 6% of patients (3). Patients presenting in the emengency room will often have nausea and, depending on

cover

conthis has

of exposure

(9).

of oxygen and hemoglobin. It displaces oxygen because the affinity of hemoglobin is 200 to 290 times greater for CO than for oxygen. A small quantity of CO can reversibly inactivate a substantial percentage of the oxygen-carrying capacity of the blood. The sigof a small amount of carboxyhemoglobin is seen in the tremendous reduction

length

canboxyhemoglobin

in concentrations

a higher

adults

vere

Approximately

may

and

the

million can produce notable effects on The inhalation of a 1% concentration is a nesting man in 30 to 40 minutes and to in 10 minutes. A concentration ofO.01% headache and 0.2% produces coma.

nc

(4-6).

or

there

ed (1 1). CO

tration tense

sequelae

the amount

the patient’s level of responsiveness on admission to the hospital and development of neuropsychiatnic sequelae (4, 5). The half-time of excretion for low concentrations is from 2 to 4 hours (8); higher concentrations may take 7 to 10 days to be completely eliminat-

the gasoline-burning internal combustion engine, which produces exhaust gases containing between 5 and 9% CO, stimulated an increased use of this gas as a suicidal agent (1). The incidence of nervous and mental sequelae following CO poisoning was first reported to be 0.8% in 1936 (2). More recent reports describe a remarkable increase in the incidence of aftereffects to between 1030% (3-6). Between 60 and 75% of patients with carbon monoxide poisoning survive the initial trauma, and 15-40% of those who survive have neuropsychiatdevelop neuropsychiatric posune (2, 6). CO acts by displacing molecule and shifting

with

monoxide

spectrum tenioration

reactions

have

have

been

of

negative within

after

carbon

increasing

neurological

several

and are either

days

and psychiatafter

discharged

monoxconcern.

from

their

onigi-

the hospi-

allow to become ambulatory. Plum and asso(20) stated that “anoxia is usually severe; most are in deep coma when found but awaken 24 hours. Nearly all patients resume full activi4 or 5 days.” The patient usually does well for

2 to 21 days

and

then

of neuropsychiatric may either progress

can

develop

signs and to coma

the whole

symptoms. or death

Deor be-

BRIEF

come arrested at any point. Some patients have a second recovery period which can lead to full health (20). There is no way to distinguish those patients who will recover from those who will relapse. Laboratory tests can be of some value in cases of CO poisoning. Initial screening for toxic agents can rule out the presence ofcentnal nervous system depressants, which have been found in as many as 20% of CO ingestions

(3).

Electrocardiograms

can

reveal

inverted

T-waves and ST wave depression (6, 8). Cenebrospinal fluid pressure may occasionally be elevated on a few lymphocytes may be seen (22). Pneumoencephalogram (in patients with marked damage) shows enlarged ventricles and cortical atrophy. Over 90% of patients have electroencephalogram abnormalities, consisting ofslow waves (2 to 5 cycles pen second) oflow voltage, frequently with a frontal preponderance (10, 23-26). In general, the severer the EEG changes, the severer are the sequelae. Patients with frontal dominance most often show general and focal neurological signs and dementia. Improvements in EEG findings parallel the patient’s clinical condition (26). Sleep EEGs may predict improvement; patients who have the most REM sleep usually have the best clinical course (27). The pathological effects of CO poisoning are present in almost

all organs

of patients

who

die

from

acute

in-

toxication. However, the most important changes occur in the brain, where edema, capillary and venous dilatation, and hemorrhagic necrosis are acute (6, 9, 20,

28).

These

lesions

are

similar

to

those

resulting

from cardiac or respiratory arrest, hypoglycemia, or cyanide poisoning (5, 1 1). Later pathological changes include demyelination of the white matter (anoxic leucoencephalopathy) in contrast to the usual predominance of lesions in the gray matter during the early stages (6, 9). The demyelination is often speckled and gives a “moth-eaten” appeanance. The gray matter regions of the brain most commonly involved are Ammon’s Horn; the part of the cortex situated below the cerebral sulci, particularly levels II, III, and IV; the pallidum; the thalamus; and the Purkinje cells of the cerebellan cortex. This predictable distribution ofanoxic lesions is not consistent with the tremendously varied and unpredictable clinical

Three

constellation.

factors have been persistently identified in the production of anoxic lesions from carbon monoxide: hypoxidosis, edema, and circulatory disorders (10, 28, 29). The edema is thought to occur as a result of anoxic lesions to the vascular wall, and it brings about not only changes in the nerve and glial cells but also intracranial hypertension and compression of various vessels. Circulatory disorders are thought to arise from hypotension because of decreased output from the left ventricle (10), increased yenous pressure with poor venous drainage because of right ventricular malfunction (29), and possible obstruction of small blood vessels by swelling of the endothelium on vasospasm (30). The need of white matter for oxygen is five times less than that of gray matter

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and may been

therefore it is remarkable that the white matter show the more extensive lesions (30). This has explained by the hypothesis that white matter may be more susceptible to anoxia and edema because ofa less redundant arterial supply. Lesions may occur more frequently in the subcortical white matter because there are fewer small vessel anastomoses than in deeper cerebral white matter (10). The size of the white matter lesions and the neurological signs have been correlated in experiments with the degree of metabolic acidosis and systolic hypertension but not with the extent of hypoxia (10).

CASE

DISCUSSION

AND

TREATMENT

RECOMMENDATIONS

Our patient presented a very confusing clinical pictune. Although carbon monoxide poisoning remained the primary diagnosis, hysterical psychosis, schizophnenia, and psychotic depression were also considened as possible diagnoses. The diagnosis was difficult because ofthe patient’s bizarre behavior, the wide and frequent clinical fluctuations, and her apparent lack of dementia under amytal sedation. However, the course of severe dementia oven several years, the amnesticconfabulatory state, mutism, parkinsonian facies and gait, hyperreflexia, and the slowing on the EEG have implicated carbon monoxide poisoning as the diagnosis. We suspect that some realization of her damaged state led the patient to increase her bizarre behavior to assure herself that she still had some control over hen actions. This bizarre behavior, which disappeared duning amytal interviews, is consistent with both the hysterical and denying defense mechanisms discussed by Weinstein and Kahn (21). Consequently, amytal interviews, which eliminated the hysterical aspects, were not helpful in diagnosis. A severe depression led to our patient’s carbon monoxide ingestion. Her hematocrit of 35% secondary to beta-thalassemia may have added to her susceptibility to CO. She initially improved, and was given six ECT treatments for depression. We cannot predict what hen subsequent course would have been without ECT, but the increased metabolic demands of convulsive activity on the central nervous system may be related to the delayed onset of anoxic leucoencephalopathy (20, 28, 31). Because many physicians are unfamiliar with this disorder, patients with carbon monoxide poisoning are often not treated as the data above indicate they should be. We recommend the following regimen: I When the patient is first seen, blood should be drawn for a carboxyhemoglobin level. Although the canboxyhemoglobin level does not correlate consistently with eventual neuropsychiatnic deficits, it is useful as a guide to determine the extent of exposure be.

cause

clearing

2. Because

is relatively

of the

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of other drugs, blood and urine should be studied to determine if central nervous system depressants are present. 3. Since acidosis frequently accompanies carbon monoxide poisoning, arterial blood gases should be determined. The metabolic state of the central nervous system lags several hours behind that of the circulatony system; thus, acidosis that is not severe in the periphenal vascular system may be significant in the central nervous system, and treatment with bicarbonate may be indicated. 4. Electrocardiograms should be obtained, and patients with abnormal EKGs should be monitored for several days. The incidence of neunopsychiatric complications is higher in olden patients with decreased cardiac reserve. Consequently hypotension and anrhythmias should be actively treated. 5. All patients should be treated with hyperbaric oxygenation if possible. 6. Tranquilizing drugs that decrease REM sleep should be avoided. 7. Because of the occurrence of edema, treatment with an agent such as dexamethasone or mannitol should be considered (26). Normal cenebrospinal fluid pressures cannot rule out central nervous system edema in CO poisoning. 8. Bedrest for 2 to 4 weeks seems necessary to avoid delayed onset of neunopsychiatnic symptoms. Although the exact etiology of this delayed onset is not known, there is a clear correlation between the onset of delayed symptoms and increased patient activity. Any activity that involves decreased perfusion of the central nervous system on increased central nervous system metabolic activity should be avoided (28). ECT should be particularly avoided following exposure to carbon monoxide (31). Although these measures are more extensive than those currently used in most hospitals, we think they are medically indicated and economically feasible. The cost of long-term psychiatric hospitalization for patients with permanent neuropsychiatric sequelae of CO damage is much greater than the cost of prompt and appropriate management of patients exposed to carbon monoxide. Because the pathology and pathophysiology of all types of anoxic encephalopathy appear to be similar to carbon monoxide poisoning, it may be worth considering extending this treatment regimen to all patients who have experienced anoxic episodes.

REFERENCES I . Beard RR, Grandstaff bra] function. Ann 2. Shillito FH, Drinker vous and mental JAMA 106:669-674, 3. Smith iS, Brandon years’ experience 46:65-70. 1970 4. Smith JS, Brandon

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N: Carbon monoxide exposure and cereNY Acad Sci 174:385-395, 1970 CK, Shaughnessy TJ: The problem of nersequelae in carbon monoxide poisoning. 1936 5: Acute carbon monoxide poisoning-3 in a defined population. Postgrad Med J S: Morbidity

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