^y o ^ c N^uro - TheTruthAboutStuff.com

N^uro0CAhd ^^d/C o ^" C 1
c)

^y

CHAPTER 14

Methyl, alcohol

STUART A. SCHNECK

Department of Neurology, University of Colorado Medical Center, Denver, Colo.

The clinical presentation of methyl alcohol intoxi- ingestion (methylated Jamaica ginger, lemon ex-

cation in humans may vary from one extreme tract, essence of peppermint and lemon, and va-

which mimics an intracranial catastrophe to a rious patent medicines)._ Despite occasional re

more subtle picture which may consist only of -portsfeiuhmanxctowiehyl

vague constitutional symptoms and a mild visual alcohol as early as 1855 (MacFarland 1855) y-L-

disturbance. When many patients with similar gorous denial of the ,poisonous character of this

complaints and physical findings arrive at a hos- substance persisted until the second decade of this

pital emergency room within a short space of _ century. A prime reason for this was economic. In_

time, it is not difficult to infer that an intoxicant 1904 untaxed methanol cost 50c. a gallon, while

might be the responsible etiologic agent. Such a taxed ethanol cost $ 2.60 per gallon (Wood and

diagnosis is, however, much more difficult when Buller 1904). Ignorance of, or ignoring, the

one deals only with a single case. Consequently, hazardous properties of this agent, abetted by in-

the broad spectrum of methanol poisoning deser- adequate product-warning labels, finally was dis-

ves the attention of neurologists. pelled by Wood and Buller, who in 1904 docu-

Methyl alcohol (CH3OH, methanol, wood al- mented 275 cases of blindness or death related to
cohol) was produced initially by wood distillation methyl alcohol usage.

and fractionation, yielding a liquid with a ter rible At the present time, methanol-containing li-

taste and odor (Wood 1912). By 189'). production quids still are used by alcoholics as cheap intoxi-

refinements had resulted in inexpecsive methods cants or as a temporary alternative when ethanol

of deodorizing methanol. Consequently, the al- is not available for consumption. Disasters occur

cohol rapidl became used in industry as a sol- when higher than expected proportions of methyl
vent, as welly in the manufacture of paint, rub- to ethyl alcohol are ingested. For example, in

ber, synthetic textiles, linoleum, shoes and dyes. Kentucky an alcoholic drink called `heads' was

It was utilized also as a cheap substitute for eth 1 made from a brand of shellac thinner costing

(grain) alcohol for external purposes such as lini- $1.95 per gallon and which contained 51.4-

ments and toiletries (Columbian spirits, bay rum, 61.5% ethanol and 2.45-2.84% methanol, by

cologne water, witch hazel, standard wood spirits), volume (Kane et al. 1968). This was diluted 1-2

as one of many adulterants used to denature times, put into half-pint bottles and sold for a

(make unfit to drink) products containing ethanol, profit of 100-200%. Little apparent injury result-

and even as an additive to products designed for ed from this practice but when a shellac solvent

References, P. 853 351

352 S. A. SCHNECK

containing 74% methanol and 0.5% ethanol, by 26 mg/I and another has 40-55 mg/l (Murphre e .x
volume, was used inadvertently, 18 people were et al. I966; Majchrowicz and Mendelson 1971).
poisoned, eight of whom died. Other outbreaks Six Russians were noted to drink 4 liters of 40%
have been reported in groups or individuals that methanol without sequelae (Rae 1946), while, by
ingested antifreeze, adulterated vodka (Tonka- contrast, blindness has resulted from the intake_
bony 1975) and sake, mixtures of inflammable of as little as 4 ml in one instance (Rae 1943;
liquids and carbonated beverages, duplicating Bennett et al. 1953) and two teaspoonsfull in
fluid (Tonning et al. 1956), etc. The largest num- another. In the Atlanta epidemic, 15 ml caused a
ber of individuals reported affected at any one fatality, while another person drank 500 ml and
time has been 323, of whom 41 died, in an out- survived (Bennett et al. 1953). The reason for this
break in Atlanta in 1953 (Bennett et al. 1953). individual susceptibility is not known, although in
Many persons were affected during Prohibition in some cases the concomitant ingestion of ethyl al-
the United States when the use of ethyl alcohol as cohol may be protective, as noted below. Recently
a beverage was illegal and substitutes were sought. the endogenous production of methyl alcohol has
For example, 400 fatalities_ were recorded during been described. An enzyme which forms methanol
one 7-month period at that time (Cooper and from adenosylmethionine is present in the pituit-
Kini 1962. Similar restraints on the use of ethyl ary gland of several mammals, including man, and
alcohol in the military have resulted in many in- can be used as a marker denoting the tissue of
stances of poisoning with methyl alcohol. It has origin of certain tumors (Snyder et al. 1967).
been estimated that 6% of all cases of blindness
in the U.S. Armed Forces during World War II SYMPTOMS AND SIGNS
resulted from methanol (Potts and Johnson
1952; Cooper and Kini 1962). Lately, methyl al- From the many cases described in the literature a
cohol largely has been removed from a number of fairly complete clinical picture of intoxication has
products, such as antifreeze and synthetic fuels, emerged (Bennett et al.1953; Roe 1955; Krishna-
and it is to be hoped that the incidence of poison- murthi et al. 1968). However, the course in any
ing will be reduced significantly_ one patient may be highly individualized and
there is no good correlation between the severity
Ingestion is not the only method of methanol of the symptoms and the quantity of methyl alco-
poisoning, for inhalation of fumes in concentra- hol consumed. Following ingestion, an asympto-
tions exceeding 200 p.p.m. in air (Bennett et al. matic latent period of 12-24 hours usually occurs,
1953; Walsh and Hoyt 1969; Dreisbach 1974) or although transient symptoms may be noted in as
absorption through the skin can cause serious or short a period as 1 hour, or illness may be deferred
fatal intoxication. Blindness has been reported in for more than 48 hours (Cooper and Kini 1962).
a factory worker who accidentally spilled a gallon When symptoms and signs do appear, characteris-
of methanol on a trouser leg (Cooper and Kini tically they involve the visual apparatus. the cen -
1962). The possibility of intoxication in infants in tral nervous system_(grs),.the.gastrointestinalsys-
Argentina whose skin was rubbed with a metha- tem and the respiratory tract.
nol contaminated rubbing alcohol has been r e-
ported recently (Wenger 1975). Visual disturbances are noted by most patientl
and vary from initial complaints of a diminished
There appears to be a wide variation in the sensation of light and mild photophobia to blur-
ability of individuals to tolerate the ingestion of red or indistinct vision, often .described as the
methanol without developing toxic signs (Chew perception of dancing spots, the presence of skin
et al. 1946). Varying amounts of the alcohol are over the eves, or flashes of grayish, whitish or
imbibed frequently by many alcoholics during the yellow vision as in a snow storm (Chew et al.
course of almost daily drinking, without evident 1946; Benton and Calhoun 1952; Benton and
consequences. Even so-called `social' drinkers con- Calhoun 1953; Bennett et al. 1953). Characteris-
sume small amounts of methanol, for in one popu- tically, the sensorium is clear at this time . Blind-
lar brand of vodka there is 3.9 mg/l of methanol, ness, either partial or complete, develops in many
while one particular brand of bourbon has

References. p. 358

MEFHYL ALCOHOL 353

patients who are poisoned severely and may come the severity of the visual symptoms and signs. (/)r I
on within hours or develop gradually over several Conversely, some patients without symptoms have
days or weeks. One patient developed blindness had objective changes in the fundi. Rarely, chronic
-0 minutes after ingesting half a pint of liquid drinkers of small amounts of methyl alcohol who
containing 35-4O% methanol (Bennett et al. then acutely consume a large amount may have a
:953). low incidence of early visual complaints, perhaps
due to an acquired tolerance to the agent (Kane
Examination of the visual apparatus often dis- et al. 1968). This may happen despite the presence
:loses pupils that react sluggishly or not at all to of blood levels of methanol that would be toxic or
:fight. Even in the absence of objective evidence of fatal for previous nondrinkers. Discovery of such
visual loss, the pupils may be dilated and react patients allows the institution of therapy before
,00rly (Bennett et al. 1953 ). Accurate early assess- the establishment of significant levels of the
:neat of visual acuity may be difficult because of breakdown products of methyl alcohol, thus pre-
the patient's mental state, the presence of - venting many visual complications.
sure keratitis and myd riasis (Krolman and Pidde
1968), but in severe cases acuity may be diminish- Common central nervous symptoms (Bennett
ed significantly. Total bilateral blindness may be et al. 1953) include headache in approximately
present within a few hours or days. The optic two-thirds of patients, dizziness in about a third
nerve may be severely hyperemic but occasionally and feelings of generalized weakness and malaise.
it may appear normal in a patient with severe Severely intoxicated patients may rapidly develop
visual loss, indicating the presence of retrobulbar seizures, stupor and coma. Unconsciousness may
neuritis (Duke-Eider 1954) . Mild or severe edema sometimes develop extraordinarily rapidly in pre-
of the optic disc and the surrounding retina may viously relatively asymptomatic individuals. Pos-
be noted within 6-24 hours, with the retinal ode- sible involvement of the peripheral nervous sys-
ma being most extensive along the course of t he tent is suggested by the histories of some patients
major retinal vessels (Benton and Calhoun 195 2). who complain of tingling and paresthesiae in the
In the peripapillary region, the retinal edema is extremities. The muscular system may be involved
chiefly in the nerve fiber layer (Krolman and since severe muscle aching and tenderness in the
Pidde 1968). Arterial spasm is sometimes present back and legs may be prominent complaints.
and the retinal veins usually are engorged. A neurological signs include varying degrees of
cherry-red spot in the foveal area may be present, mental confusion, memory loss and amnesia. Sev-
presumably related to retinal ischemia (Cerasoli ere apprehension, maniacal behavior and deli -
1971). The earliest visual field defect u«lly is_a rium may occur. Reports of focal weakness are
cecocentral or central scotoma, while later on rare and rio case of permanent paralysis has been
more complex types gf_field_defects.jnay_appear. reported. A syndrome of `pseudomeningitis' has
Infrequently, the shapes of the initial scotomata been described (Bennett et al. 1953) consisting of
may differ between the two eyes despite similar headache, vomiting, coma, bradycardia, hyper-
ophthalmoscopic appearances. Further examina- tension, dilated nonreactive pupils, rigid neck and
tion eventually may disclose optic atrophy of the generalized hyperreflexia. Such patients may die
primary type, while occasional deep cupping of the in as short a time as 15 minutes from the onset of
nerve head may simu ate glaucomatous atrophy symptoms.
(Fridenberg 1911). Discrete retinal hemorrhages
and decreased intraocular tension have been Gastrointestinal complaints are frequent (Ben-
- noted in some eyes. Other ocular abnormalities nett eta . 1953), with anorexia and severe ab-
found occasionally have been vtosis. extraocular dominal pain being outstanding manifestations of
muscle palsies and nystagmus. - the disorder. The pain may simulate that of an
acute abdominal crisis and be accompanied by
In mild cases, and even in some with a fatal out- deep tenderness and abdominal wall rigidity. At
come, the fundi have appeared normal (Krolman times renal colic has been suggested by the des-
and Pidde 1968). Often poor correlation has been criptions of the pain. Nausea is frequent and vo-
noted between the funduscopic appearance and miting may occur.

References, p. 358

354 S. A. SCHNECK

Some patients may notice dyspnea, but often in the few patients in which it has been utilized,

the respirations are slow (Bennett et a]. 1953). for all parameters of stimuli fail to elicit a normal

Despite the presence of severe acidosis (see below), beta wave (Praglin et al. 1955; Ruedemann 1961;

Kussmaul respirations are rare (Goodman and Cooper and Kini 1962).

Gilman 1975). Some patients exhibit a rapid and Electrocardiograms have on occasion disclosed

shallow breathing pattern and severely affected diminished T wave voltages in leads I and II wit h

patients may develop both cyanosis and rubeosis. reversion to normal after therapy of the acidosis

A few patients may have hypertension. Despite (Weisberger and MacLaughlin 1947). It is un-

t e appearance of systemic shocT m some indi- likely that this is a change specific for methyl alco-

viduals, hypotension is rare. hol poisoning . A more recent report azra et al .

1974?suggestsE methyl alcohol as a c

LABORATORY DATA deleterious a ect on the right h ea , Inducingan

electrocardiographic pattern of right ventricular

The most important laboratory finding in pa- strain. This was evidenced by right atrial over-

tients with methyl alcohol intoxication is that of load, clockwise rotation and in some cases, right

acidosis, for the severity of visual and general axis deviation.

symptoms relate more directly to this than to the Rarely gas has been noted in the entire portal
level of methanol itself in blood or tissue (Ree
1943). The pH of the blood is low (in severe cases /venous system on abdominal X-rays (after anti- .^ ?C

freeze in stion), secondary to an acute necrotiz

approaching 7.0), as is that of urine (pH may -ingastroeiwchausedArtionf

reach 5). Serum bicarbonate also is reduced mar- ` v se1 wau1cFink and Boyden 1966).

kedly and in desperate cases CO 2 combining METHANOL METABOLISM AND
power is often less than 20 mEq/l. When this has DISEASE MECHANISMS
occurred, approximately 25% of such patients
have died and in some of these the CO 2 combin-

ing power fell to zero. Moderate ketonemia and Degradation of methanol in humans is slow and

acetonuria also may occur. one-third of an ingested dose can remain in the

Sodium and potassium levels in the blood body unaltered for 48 hours, with some remaining

usually are normal, but vigorous bicarbonate for as long as a week. Approximately 2-10% is

therapy for the acidosis may result in hypokale- excreted unaltered through the kidneys and most

mia if care is not taken. Serum amylase elevations authors indicate that a similar small amount exits

related to the presence of pancreatitis have been unchanged through the lungs (Leaf and Zatman

found in many cases (Bennett et al. 1952). Hyper- 1952; First et al. 1970). Some investigators, how-

glycemia and elevations of lactate and pyruvate ever, indicate that amounts greater than 20% may

levels of blood may also occur, but likely are relat- leave via this portal (Keeney and Mellinkoff 1951;

ed to the presence of shock and acidosis (Crook Cooper and Kini 1962). The vast majority of me-

and McLaughlin 1966). Albuminuria sometimes thyl alcohol in primates and man is oxidized to

has been found in severe cases. formaldehyde by an alcohol dehydrogenase in the

Some reports have indicated that csr pressures liver and kidney. This same enzyme then breaks

are elevated, probably related to the presence and formaldehyde down to formic acid (Abeles and

degree of cerebral edema, but this is not an in- Lee 1960). Formic acid is six times and formalde-

variable finding (Reiner 1950). csF protein and hyde 33 times as toxic as methanol (Fink 1943). It

glucose content and cell counts have been normal. is likely .that the asymptomatic latent period

Electroencephalograms have been diffusely noted above is terminated when these substances

slow in severely poisoned patients, again correlat- rise to significant levels and then exert their toxi-

ing more with the degree of acidosis than with city. About 40% of ingested methanol is excreted

blood or csF levels of methanol (Jameson and via the kidneys as formic acid (Keeney and Mellin-

Kane 1969). koff 1951), reaching an amount 100 times normal

The electroretinogram also has been abnormal (Morgan and Cogan 1974). Some of the formic

Ref-races. p. 358

METHYL ALCOHOL 355

acid in the body is further oxidized to CO2 and centration of methanol in gastric juice is 5-12
H20. Maximum values of formic acid in the times greater than that in blood, even 10 days
urine are achieved 1-2 days after ingestion, but after ingestion (Cooper and Kini 1962). Absorp-
excretion continues for from 4-10 days (Morgan tion is rapid from the gastrointestinal tract, and
and Ccgan 1974). The use of alcohol dehydrogen- the alcohol is thought to be re-excreted into the
ase to metabolize methanol is not universal in all stomach for many days during the course of
species. A catalase system is active in most other severe poisoning (Bennett et al. 1953).
animas and the failure to recognize this different
route of metabolism caused considerable confu- Methanol levels in blood and urine may be
sion in the literature until recently (Mannering measured by gas chromatographic methods (Ba-
et al. 1965; Kane et al. 1968). ker et al. 1968). The breakdown product formic
acid is a normal constituent of urine (Closs and
It is generally agreed that the severe and inju- Solberg 1970), but in poisoning cases it may also
rious metabolic acidosis associated with methyl be found in the blood. Sometimes formaldehyde
alcohcl poisoning is from the process of meta- appears in the urine as well. The amounts of these
bolism and not from the alcohol itself (Rae 1969). two substances found in blood or urine are direct-
Form'.: acid is thought to be the major cause of ly related to the amount of methanol consumed.
decrease in the pH and CO 2 content of the blood Measurement of serum osmolality can be a guide
(Roe :943; Clay et al. 1975), while formaldehyde to the identification of the amount of methanol
is thought by many to be the agent specifically in- ingested in cases of poisoning (Glasser et al. 1973;
juriou to the retina. Roe (1943) believes that Stern 1974).
acidosis in general and hypoxia also play a role in
the re_inal injury. Consequently, substances which The lethal amount of ingested methanol is
delay the oxidation of methyl alcohol are of assis- quite variable. One reason for this may ba the
tance in the treatment of poisoning. One such lack of correct historical data from the involved
agent is ethyl alcohol since it too uses the alcohol alcoholics. The usual fatal dose is between 30-
dehydrogenase system for oxidation (Roe 1943; 250 ml (First et al. 1970), but as much as 540 ml
Li and Vallee 1969). The enzyme will metabolize has been swallowed without irreversible toxicity.
ethanol preferentially if the two drugs are both The alcohol itself infrequently causes death due to
present in the body. Methanol metabolism is also cNs depression (Potts et al. 1955), whereas the
5-7 times less rapid than that of et anol an acidosis is the major reason for fatalities.
proceeds independently of the concentration of
methanol in the blood. Therefore, if the oxidative Mean cerebral blood flow and cerebral oxygen
enzyae is tied up by ethanol, more methanol can consumption have been reduced by as much as
be excreted unchanged from the body with less 30% in acute cases of poisoning, and these levals
resu::ant toxicity (Rae 1950). This fact is taken rise towards normal with recovery (Battey et al.
advantage ofjn treatment, as will be noted below. 1956). It appears likely that cerebral edema and
$ec twC4-methylpyrazol has bee n found to vessel wall swelling cause increased vascular resis-
inhicit alcohol e y rogenase specifically and may tance to blood flow, and that acidosis itself has a
possibly prove useful in the treatment of methanol direct toxic effect on the brain, thus diminishing
intoxication (Blomstrand and Theorell 1970; oxidative processes.
Lester and Benson 1970; Murphy an Watkins
197:: Salaspuro et al. 1975). The specific retinal cell toxicity of one of the
degradation products, formaldehyde, is the ac-
When methanol enters the body it is distributed cepted cause of the visual symptoms and signs in
throughout the tissues in relation to their water primates. The retina has a greater oxygen con-
content (Cooper and Kini 1962). The aqueous and sumption via aerobic glycolysis in proportion to
especially the vitreous humors of the eye thus its iron content than any other tissue. Formalde-
acquire the highest concentration of the alcohol hyde has been found to interfere with ATP gen-
(Benton and Calhoun 1952), while it is also quite eration, to uncouple oxidative phosphorylation
elevated in gastric juices and csr. Indeed, the con- and possibly also to inhibit anaerobiclvcolvsis
(Potts and Johnson 1952; Cooper and Marchesi
1959; Cooper and Kini 1962; Kini and Cooper

Rejmraces, p. 358

356 S. A. SCHNECK

1962). Thus, as a result of its toxicity to retinal years after the ingestion of methanol. Recently a
glycolysis and respiration, formaldehyde has been case has been reported involving a 13-year-old
the substance postulated to cause the degenera- girl who drank antifreeze (Guggenheim et al.
tion of retinal cells, with resultant blindness. 1971). Rigidity, spasticity, and hypokinesis

PROGNOSIS developed 4 weeks after ingestion, with the rigid-
ity being improved by levodopa.

The outlook for survival is dependent mainly on
the degree of severity of the metabolic acidosis PATHOLOGICAL FFIINNDDIINGS

and the effectiveness with which it is treated. In most fatal cases, congestion, edema and some

Only in unusual cases does the narcotic effect of minor hemorrhages have been found in many or-

very high levels of methanol itself influence mor- gans (Menne 1938). Hemorrhagic pancreatic ne-

tality (Goodman and Gilman 1975). Coma and crosis is particularly common (Burhans 1930;

seizures are not always indicative of a hopeless Bennett et al. 1952). The brain has been variably

prognosis. Death from acidosis may be associated edematous with meninge al and subaracnoid

with a peculiar cessation of respiration, which petechiae being prominent (Burhans 1930; Branch

sometimes occurs within minutes. Breathing be- TdnningT945). Pet cch ae have been especially

comes slow and shallow, after which tonic con- numerous in the region of t he Ilyd ventricle, ague-

traction of the limbs and opisthotonos may occur, duct of Sylvius and beneath the floor of the

followed by a great gasp and respiratory cessation _IVth ventricle. Ischemic necrosis of all three lavers

with the chest locked in inspiration. The heart of the cerebellar cortex also has been noted. Bi-

may continue to beat for a few minutes before lateral necrosis of the putamen _i nvolving both +t om

failing (Roe 1955). neurons and glia with cyst formation has been

With regard to vision, the absence of a pupillary regarded by some as specific forhte^ oxis effect 9

light reflex is generally a poor prognostic sign for methanol on the brain (Orthner99SO; Potts et al. /

life, and for eventual restoration of visual acuity 1955). Experimentally, primates poisoned with ^^

(Benton and Calhoun 1952). Those who die are methanol have been shown to develop edema and

almost always blind or nearly so (Roe 1950). All nuclear pyknosis in the putamen and caudat e

patients with severe retinal edema usually are left nuclei. One patient has been reported who had

with some degree of permanent visual loss. slits-haped cysts in the lateral parts of the p tame-
Fortunately, however, most patiel is do make a na at autopsy 1 year after methanol intoxication

partial or complete recovery from their initially while another who died acutely had hemorrhages

diminished visual acuity. Some even do so within in -the putamina and adjacent tissue (Erlanson

the first hour after treatment of the acidosis. If et al. 1965).

vision does not return fully to normal within Some conflict appears in the literature with re-

6 days after the onset of therap y, it usually will _ gard to the ocular pathology of methanol. Some

decrease again to a low level. The longer the initial reports indicate that no retinal changes are spe-

visual loss is present prior to the onset of therapy, cific for methyl alcohol (McGregor 1943), es-

the less likely it is that full vision will be regained, pecially in patients who die early. Others would

because of arterial attenuation and primary dismiss any changes found as being related to

optic atrophy (Roe 1953; Krolman and Pidde post mortem degeneration. Most authors, how-
1968). The latter is usually well established in ever, indicate that ante mortem degeneration of

1-.2 months. retinal ganglion cells is common (Fink 1943; Rage

Until recently only the German literature con- 1955; Cooper and Kini 1962). These cells may

tained a few references to persistent focal neuro- show evidence of central chromatolysis, and the

logical defects other than optic atrophy (Riegel degeneration extends into the inner and outer re-

and Wolf 1966). These involved the development tinal granular layers. Choroidal vessels are con-

of focal cranial nerve defects and a Parkinsonian- gested and the rod and cone nuclei appear irregu-

like extrapyramidal syndrome coming on many lar. Secondary degeneration occurs in the optic

References, p. 358

MUNYL ALCOHOL 357

nerves, which also may exhibit edema, hyperemia and glucose must be given in the intravenous solu-
and associated gliosis. tion to prevent hypoglycemia. Therapy may be
stopped after a few days when blood methanol
The possibility of lateral geniculate body ne- levels are below 20 mg/% and no acidosis is pres-
crosis has been raised in one patient with a typical ent.
clinical course for methyl alcohol intoxication,
but in whom laboratory substantiation of this Massive alkalinization is another mainstay of
agent could not be made (Messen 1972). therapy (Chew et al.1946; Roe 1969). 1.5 liters or
more of 5% NaHCO 3 in 5% glucose should be
THERAPY given rapidly and frequently enough to correct
acidosis (Roe 1969) which is monitored by
A tripartite approach to treatment involving the serum HCO 3 and CO 2 levels and blood pH, and/
we of ethanol and bicarbonate and, in severe or by arterial blood gases. Another authority re-
cases, dialysis has been developed to deal with commends giving 3 mEq of bicarbonate/kg of
s'.gnificant instances of methyl alcohol poisoning. body weight (Rumack 1976a). In one major
Rational therapy depends on frequent monitoring epidemic, when commercially prepared solutions
cf methanol, CO2, bicarbonate and pH levels in of bicarbonate were not available, 50 g of com-
the blood. mon baking soda for kitchen use was put into a
liter of 5% dextrose in water and given intra-
The first parameter of treatment is the use of venously, with only one pyrogenic reaction oc-
et y a cohol to saturate the alco of dehydrogen- curring with every 200 liters used (Bennett et al.
.se enzyme and thus avoid a build-up of the toxic 1953). Rapid alleviation of symptoms has been
products of metabolism (formaldehyde and formic noted frequently as the serum bicarbonate rises
acid) (Roe 1946; Gilger et at. 1956; Gilger et al. toward normal.
1959; Gervais 1966; Li and Vallee 1969). This
allows for an increase in excretion of unchanged Inasmuch as methanol is present in gastric
methyl alcohol through the lungs and kidneys, juice and is reexcreted over a period of time into
also aided by giving high volumes of fluid to the stomach, some advocate giving syrup of
force diuresis (Kane et al. 1968). One schedule ipecac to induce vomiting if the patient is seen
suggests giving 1 ml of ethanol (100 proof)_p r within two hours of the ingestion (Dreisbach
kilogram of body weight at once and 0.5 ml/kg 1974). Gastric lavage, though not used by all be-
of boyiwijli every 2-4 hours, o maintain a cause of fear of perforation of the stomach, has
blood level of 100 mg% or higher for 1-4 days been advocated by many as another way ofremov-
(Lawrence and Haggerty 1971). Another schedule ing methanol in comatose patients, in those hav-
indicates that the attainment of an initial blood ing seizures or when the gag reflex has been lost
level of 100 mg% of ethanol requires that I g of (First et al. 1970). Two to four liters of 3% solu-
this alcohol should be given for each liter of total tion of NaHCO 3 is used for lavage.
body water (total body water is 60°x, in liters, o f
the kilogram weight) (Rumack 1976a). The appro- It is important to realize that the metabolism of
priate amount of ethanol should be given intra- methanol is slow and that treatment with bi-
venously over a 10-15 minute period. Fifty per- carbonate should be carried out for 3-5 days
cent ethanol solutions contain 400 mg/ml on a to avoid relapses. Cases have been reported of
weight/volume basis, 420 mg/ml on a weight/ premature cessation of treatment with resultant
weight basis and 480 mg/ml on a volume/volume relapse as late as the fourth day after ingestion.
basis. For maintenance, at least 7-10 g of ethanol Attention must also be paid to the level of serum
should be given per hour (which is the excretion potassium, which tends to drop with bicarbonate
rate for this substance by a normal adult) but
chronic alcoholics may require replacement of as therapy.
much as 20-30 g/hr (Rumack 1976b). Frequent
blood level determinations for ethanol are neces- The last therapeutic measure recommended is
sary to accurately monitor this form of treatment dialysis. Hemodialysis, first used in 1961.(Marc-
Aurele and Schreiner 1960; Austin et al. 1961;
Shinaberger 1961; Wieth and Jorgenson 1961) is
usually employed when the blood methanol con-

References, p. 358 Jc x l.}- ^f } r+

Z ()

358 S. A. SCHNECK

centration is over 50 mg% in an acidotic, clinically CHEW, W.B., E.H.BERGER, O. A. BRINES and M.J.CAPRON:
ill patient (Cowan 1964). Therapy with ethanol Alkali treatment of methyl alcohol poisoning. J.
and bicarbonate is pushed while the dialysis is
being set up. The procedure produces a rapid fall Amer. med. Ass. 130 (1946) 61-64.
in serum methanol levels and results in a speedier
CLAY, K. L., R. C. MURPHY and w. D. WATKINS: Experi-
mental methanol toxicity in the primate: Analysis of
metabolic acidosis. Toxicol. appl. Pharmacol. 34

recovery with fewer sequelae than is achieved with (1975) 49-61.
alkalinization and ethanol treatment alone
(Keyvan-Larijarni and Tannenberg 1974). Peri- CLOSS, K. and c.o.soLBERG: Methanol poisoning. J.
toneal dialysis is also successful but is slower than Amer. med. Ass. 211 (1970) 497- 499.

COOPER, J.R. and M.M.Knvu: Biochemical aspects of
methanol poisoning. Biochem. Pharmacol. 11

hemodialysis in correcting the metabolic abnor- (1962) 405-416.
malities (Wenzl et al. 1968).
COOPER, J.R. and V. T. MARCHES!: The possible bio-
chemical lesion in blindness due to methanol poison-

REFERENCES ing. Biochem. Pharmacol. 2 (1959) 313-315.
COWEN, D.L.: Extracorporeal dialysis in methanol

ABELES, R.H. and H. A. LEE, JR.: The dismutation of for- poisoning. Ann. intern. Med. 61 (1964) 134-135.
maldehyde by liver alcohol dehydrogenase. J. biol. CROOK, J.E. and J.S. MCLAUGHLIN: Methyl alcohol
Chem. 235 (1960) 1499-1503.
poisoning. J. occup. Med. 8 (1966) 467-470.
AUSTIN, W.H., C. P. LAPE and H. N. BURNHAM: Treatment DREISBACH, R.H.: Handbook of Poisoning, 8th Ed.
of methanol intoxication by hemodialysis. New
Engi. J. Med. 265 (1961) 334. Los Altos, Lange Med. Publ. (1974) 145-147.
DUKE-ELDER, s.: Textbook of Ophthalmology. VI. In-`
BAKER, R. N., A. L. ALENTY and J. F. ZACK, JR.: Toxic
volatiles in alcoholic coma. A report of simultane- juries. Saint Louis, Mo., C.V. Mosby (1954) 6816-

6821.

ous determination of blood methanol, ethanol, iso- ERLANSON,P., H.FRITZ, K.E.HAGSTAM, B.LILJENBERG,

propanol, acetaldehyde and acetone by gas chro- N. TRYDING and G. VOIGHT: Severe methanol intoxi-
matography. Bull. Los Angeles neurol. Soc. 33 cation. Acta med. scand. 177 (1965) 393-408.

(1968) 140-144. *FINK, D.w. and F.M.BOYDEN: Gas in the portal veins.

BATTEY, L. L., J. L. PATTERSON, JR. and A. HEYMAN: Ef- 'i A report of two cases due to ingestion of corrosive =- J

fects of methyl alcohol on cerebral blood flow and substances. Radiology 87 (1966) 741-743. ^^H

metabolism. Observations du ring and after acute A PINK, w.H.: The ocular pathology of methyl-alcohol

intoxication. Arch. Neurol. Psychiat. (Chic.) 76 poisoning. Amer. J. Ophthal. 26 (1943) 694-709.

(1956) 242-256. 802-815.

Ill BENNETT, I. L., JR., T. C. NATION and J. F. OLLEY: Pan- FIRST, M.R., R.JACOBSON, A. R. GOLDEN and H.C.SEFTEL:
Y1 creatitis in methyl alcohol poisoning. J. Lab. clin. Acute methyl alcohol poisoning. S. Air. med. J. 44
Med. 40 (1952) 405-409. (1970) 503-505.
;(7L05
BENNETT, I.L., JR., F. H. CARY, G.L. MITCHELL and M.N. FRIDENBERG, P.: The nerve-head in wood-alcohol
1:• COOPER: Acute methyl alcohol poisoning: A review amaurosis. Trans. Amer. oohthal. Soc. 12 (1911).

1 based on experiences in an outbreak of 323 cases.

t Medicine (Baltimore) 32 (1953) 431-463.

BENTON, C.D., JR. and F. P. CALHOUN, JR.: The ocular

effects of methyl alcohol poisoning: Report of a

catastrophe involving three hundred and twenty GILGER, A.P., A.M.POTTS ana I.S.FARKAS: Jtuates On
persons. Trans. Amer. Acad. Ophthal. Otolaryng.
56 (1952) 875-885. the visual toxicity of methanol. IX. The effect of
BENTON, C.D., JR. and F. P.CALHOUN, JR.: The ocular ethanol on methanol poisoning in the Rhesus mon-
key. Amer. J. Ophthal. 52 (1956) 244-253.

effects of methyl alcohol poisoning. Report of a GILGER,A.P., Ls.FARKAS and A.M.POTTS: Studies on

catastrophe involving 320 persons. Amer. J. Oph- the visual toxicity of methanol. X. Further observa-
thal. 36 (1953) 1677-1685. tions on the ethanol therapy of acute methanol

BLOMSTRAND, R. and H.THEORELL: Inhibitory effect on poisoning in monkeys. Amer. J. Ophthal. 48 (1959)

ethanol oxidation in man after administration of 153-161.

4-methylpyrazole. Life Sci. 9 (1970) 631-640. GLASSER, L., P.D.STERNGI.ANZ, J.COMBIE and A.ROBIN-

BRANCH, A. and D.I.TONNING: Acute methyl alcohol SON: Serum osmolality and its applicability to drug
overdose. Amer. J. clin. Path. 60 (1973) 695-699.
poisoning. Observations in some thirty cases. Ca- GOODMAN, L.s. and A.GILMAN: The Pharmacological.
Basis of Therapeutics. 5th Ed. New York, N.Y.,
nad. J. publ. Hlth. 36 (1945) 147-151. Macmillan (1975) 146-148.
BURHANS, E. c.: Methyl alcohol poisoning (A clinical

and pathological study of 1I fatal cases). Illinois

med. J. 57 (1930) 260-263. GUGGENHEIM, M.A., J.R.COUCH and W.WEINDERG:
caRASOLu, J.R.: Effects of drugs on the retina. Int.
Motor dysfunction as a permanent complication of
ophthal. Clin. 11(1971)121-135. methanol ingestion. Presentation of a case with a.

METHYL ALCOHOL 359

beneficial response to levodopa treatment. Arch. of twenty-two instances with postmortem examina-

Neurol. (Chic.) 24 (1971) 550-554. lions. Arch. Path. 26 (1938) 77-92. a
t
HAZRA, D. K., H. C. SETH, K. s. MATHUR, P.K. WAH AL, kMESSEN, M.D.: Bilateral lateral geniculate body necrosis
9C)
V.PRAKASH, B. B.MAHESHWARI and s.TANDON: Elec- as a cause of amblyopia. Neurology (Minneap.) 22

trocardiographic changes in acute methanol poison- (1972) 263-268.

ing. J. Ass. Phycns. India 22 (1974) 409-413. MORGAN, R. and E. J.COGAN: Methyl alcohol intoxica-

J.4WESON, H.D. and R.KANE: EEG records during an tion. In: B.Kissin and H.Begleiter, eds.: Clinical

epidemic of methanol intoxication. Electroenceph. Pathology. New York, N.Y., Plenum Press (1974)
clip. Neurophysiol. 26 (1969) 112.
176-189.

KANE,R.L., W.TALBERT, J.HARLAN, G.SIZEMORE and MURPHREE,H.B., L.M.PRICE and L.A.GREENBERG: Ef

s.CATALAND: A methanol poisoning outbreak in fect of congenes in alcoholic beverages on the

Kentucky. A clinical epidemiological study. Arch. incidence of nystagmus. Quart. J. Stud. Alcohol 27

environm. Hlth. 17 (1968) 119-129. (1966) 201-213.

KEENEY,A.H. and S.M.MELLINKOFF: Methyl alcohol MURPHY, R.c. and W.D.WATKINS: Pharmacology of

poisoning. Ann. intern. Med. 34 (1951) 331-338. Pyrazoles. I. Structure elucidation of metabolites of

KEYVAN-LARIJARNI, H. and A.M.TANNENBERG: Metha- 4-methylpyrazole. Biochem. biophys. Res. Coin-
nol intoxication. Comparison of peritoneal dialysis mun. 49 (1972) 283-291.

and hemodialysis treatment. Arch. intern. Med. 134 k O RTHNER, H.: Die Methylalkoholvergiftung. Berlin,

(1974) 293-296. Springer (1950).

KINI, H. M. and J. R. COOPER: Biochemist ry of methanol PLUM, F. and J. B. POSNER: Diagnosis of Stupor and

poisoning. 4. The effect of methanol and its metabo- Coma. 2nd Ed. Philadelphia, Pa., F. A. Davis ( ( 972)
lites on retinal metabolism. Biochem. J. 82 (1962) 197-198.

164-172. Porrs, A. at. and L. V. JOHNSON: Studies on the visual

KRISHNAMURTHI, N.V., A.R.HATARATAN, K.SHANMUGA- toxicity of methanol. I. The effect of methanol and

SUNDARAM, K. FADMANABHAN and K. NITYANANDAN: its degradation products on retinal metabolism.

Acute methyl alcohol poisoning. (A review of an Amer. J. Ophthal. 35 (1952) 107-113.

outbreak of 89 cases). J. Ass. Phycns. India 16 11POTns,A.M., J.PRAGLIN, J.FARKAS, L.ORBISON and

(1968) 801-805. D.CHICKERING: Studies on the visual toxicity of

KROLMAN, G.H. and W.J.PIDDE: Acute methyl alcohol methanol. VIII. Additional observations on metha-

poisoning. Canad. J. Ophthal. 3 (1968) 270-278. nol poisoning in the primate test object. Amer. J.

LAWRENCE, R. A. and R. i. HAGGERTY: Household agents Ophthal. 40 (1955) 76-83.

and their potential toxicity. Mod. Treatm. 8 (1971) PRAGLIN, J., R.SPURNEY and A.N.POTTS: An experi.

511-527. mental study of electroretinography. I. The electro-

LEAF, G. and L.J. ZATMAN: A study of the conditions retinogram in expe rimental animals under the in-

under which methanol may exert a toxic hazard in fluence of methanol and its oxidation products.

industry. Brit. J. industr. Med. 9 (1952) 19-31. Amer. J. Ophthal. 39 (1955) 52-62.
LESTER, D. and c.D.BENSON: Alcohol oxidation in rats )CREINER, E.R.: The cerebrospinal fluid in methyl alcohol

inhibited by pyrazole, oximes and amides. Science • poisoning. Arch. Neurol. Psychiat. (Chic.) 64(1950)

169 (1970) 282-284. 528-535. f1r 7

LI, T.-K. and B. L. VALLEE: Alcohol dehydrogenase and RIEGEL, H. and G. WOLF: Schwere neurologische Aus-

^O ethanol metabolism. Surg. Clin. N. Amer. 49 (1969) fille als Folge einer Methylaikoholvergiftung.

(^ 577-582. Fortschr. Neurol. Psychiat. 34 (1966) 346-351.
v1 MAC FARLAND, J. F.: The methylated spirit and some of ROE, o.: Clinical investigations of methyl alcohol

its preparations. Pharm. J. Trans. 15 (1855) 310. poisoning with special reference to the pathogenesis

MA JCHROwtcz, E. and J. H. MENDELSON: Blood metha- and treatment of amblyopia. Acta med. scand. 113

nol concentrations during experimentally induced ( ( 943) 558-608.

ethanol intoxication in alcoholics. J. Pharmacol. ROE, 0.: Methanol poisoning. Its clinical course, pa-

exp. Ther. 179 (1971) 293-300. thogenesis and treatment. Acta med. scand. Supp.

MANNERING, G.J., A.MAKAR, D.A. VAN HORKEN and 182 (1946) U-253.

T.R.TEPHLY: A species difference in the oxidation of ROE, O.: The roles of alkali salts and ethyl alcohol in

methanol. Toxicol. appl. Pharmacol. 7 (1965) 490. the treatment of methanol poisoning. Quart. J.

MARC-AURELE, J. and G. E.SCHREINER: The dialysance Stud. Alcohol 11(1950)107-112.

of ethanol and methanol: A proposed method of ROE, G.: The metabolism and toxicity of methanol.

the treatment of massive intoxication by ethyl or Pharmacol. Rev. 7 (1955) 399-412.

methyl alcohol. J. clin. Invest. 39 (1960) 802-807. ROE, o.: Past, present and future fight against methanol

MCGREGOR, I.S.: A study of the histopathological blindness and death. Trans. ophthal. Soc..U.K. 89

changes in the retina and late changes in the visual (1969) 235-242.

field in acute methyl alcohol poisoning. Brit. J. RUEDEMANN, A.D., JR.: The electroretinogram in chro-

Ophthal. 27 (1943) 523-543. nic methanol poisoning in human beings. Trans.

MENNE, P.R.: Acute methyl alcohol poisoning. A report Amer. ophthal. Soc. 59 (1961) 480-529.

360 S. A. SCHNECK

RUMACK, B.3.: Methanol. In: B.H.Rumack, ed.: WALSH, F.B. and W. F.HOYT: Clinical Neuroophthal-

Poisindez. Denver, Colo., Micromedex (1967a) M9. mology, Vol. 3. Baltimore, Md. Williams and Wil-

RuMACK, B.a.: Personal communication (1976b). kins (1969) 2582-2586.

SALASPURO.M.P., K.O.LINDR09 and P.PIKKARAINEN: WEISBERGER,A.S, and J.A.MACLAUGHLIN: Electro-

Ethanol :.nd galactose metabolism as Influenced by cardiographic changes associated with methyl aloe.

4-methylbyrazole in alcoholics with and without hol poisoning. Amer. Heart J. 33 (1947) 27-33.

nutritioc_l deficiencies. Ann. clin. Res. 7 (1975) 269-p, ` WENGER, A.J.: Methanol poisoning. J. Amer. med.

272. ' Ass. 232 (1975) 906-907.

SHINABERGZ,J.H.: Treatment of methanol poisoning WENZL, J.E., S.D.MILLS and J.T.MCCALL: Methanol

by extra-:orporeal dialysis. Arch. intern. Med. 108 poisoning in an infant. Successful treatment with

(1961) 9:7-939. peritoneal dialysis. Amer. J. Dis. Child. 116 (1968)

SNYDER, S.=., J. ALEXROD, 0.0. SMITH and C. L. PIERCE: 445-447.

Formati:n of methanol by an enzyme in an ecto- WIETH, J.o. and H. E.JORGENSEN: Treatment of metha-

pic pine=-loma. Nature (London) 215 (1967) 773- not and ethanol poisoning with hemodialysis. Dan.

774. med. Bull. 8 (1961) 103-106.

STERN, E.L.: Serum osmolality in cases of poisoning. WOOD, C.A.: Death and blindness from methyl or

New Ecll. J. Med. 290 (1974) 1026. wood-alcohol poisoning with means of prevention.

TONKABONY. S. E. H.: Post-mortem blood concentra- J. Amer. med. Ass. 59 (1912) 1962-1966.

tion of=ethanol in 17 cases of fatal poisoning from WOOD, C. A. and F. BULLER: Poisoning by wood alcohol.

contraband vodka. Forensic Sci. 6(1975)1-3. Cases of death and blindness from Columbian spirits

^^ TONNING, 7.J., D. W. BROOKS and C.M. HARLOW: Acute and other methylated preparations. J. Amer. med.

methyl _cohol poisoning in 49 naval ratings. Canad. Ass. 43 (1904) 972-977; 1058-1062; 1117-1123;

med. A. J. 74(1956)20-27. 1213-1221; 1289-1296.