Hemodialysis for Methanol Intoxication
ANDREW GONDA, M.D.
HENRY GAULT, M.D.
DAVID CHURCHILL, M.D
DAVID HOLLOMBY, MD
Montreal, Quebec, Canada
From the Renal and Electrolyte Division, Depart-
ment of Medicine, Royal Victoria Hospital, McGill
University, Montreal, Quebec, and the Faculty of
Medicine, Memorial University of Newfoundland,
St. John’s, Newfoundland. Requests for reprints
should be addressed to Dr. AndrewGonda,Renal
andElectrolyteDivision,Departmentof Medicine,
Royal Victoria Hospital,Montreal,Quebec, Can-
ada. Manuscriptaccepted September 19, 1977
We describe nine patients with methyl alcohol poisoning who were
treated with hemodialysis. The time from ingestion to dialysis varted
from 4 to 100 hours. Predialysls blood methanol levels ranged from
3 to 570 mg/dl. All patients were acidatlc and had an increased anIon
gap. Two patients died, seven recovered, but three had permanent
visual impairment. There was little correlation between the blood
methanol level or anion gap and visual outcome. The interval from
ingestion to treatment appears to be more important than the initial
biochemical status. We recommend prompt hemodiaiysis if the blood
methanol level is above 50 mg/dl, when an amount of methanol
exceeding the minimal lethal dose (30 ml) is known to have been
ingested, when there Is evidence of acidosis or when an abnormality
has developed In vision, funduscoplc examination or mental state.
Concurrent therapy with alkali and ethanol is vital.
Methanol has a special place among the dialyzable poisons. Symptoms
of methanol poisoning may be delayed for 12 to 18 hours, and this
latent period is thought to correspond to the time required for methanol
to be metabolized to the more toxic formaldehyde and formic acid.
Weakness, headache, nausea, epigastric pain and impaired vision are
the usual presenting symptoms and may rapidly be followed by
blindness, coma and cardiac arrest [ 11. A severe metabolic acidosis
with an increased anion gap is frequently present. Control of acidosis
with bicarbonate administration, and delay of methanol metabolism
by the administration of ethanol, appear to greatly increase the survival
rate and may prevent ocular damage. There are reports of the use of
hemodialysis in the treatment of at least 26 patients with methanol
intoxication [ 2- 141. We wish to review these reports and present our
experience with an additional nine patients treated with hemodialysis,
alkali and ethanol, and advocate indications for this combined ap-
proach which are more liberal than those previously proposed.
METHODS
Blood methanol levels were determined by a calorimetric method [ 151 in the
first eight patients and serum methanol levels by gas-liquid chromatography
in the ninth [ 161 with a sensitivity of approximately 2 mg/liter. Blood gases
were determined using an Instrumentation Laboratory Inc., pH gas analyzer,
Model 113 (Boston, Mass.). Other biochemical parameters were determined
using standard Technicon@ Automated Methodologies (Technicon Corp.,
Tarrytown, N.Y ). Seven patients (Cases 1 through 7) were dialyzed with a
Travenol RSP dialysate delivery system (Travenol Labs Inc., Deerfield, Ill.)
using EX023 coils (Extra Corporeal Medical Specialities Inc., King of Prussia,
Pa.). The remaining two patients (Cases 8 and 9) were dialyzed using a Drake
Willock single pass delivery system (DWS, Inc., Portland, Ore.), and a CDAK
Model 5 hollow fiber dialyzer (Cordis Dow Corp., Miami, Florida).
May 1979 The American Journalof Medicine Volume 64 749
 ~MOi%UYSlS FOR METHANOL INTOXICATION-GONDA ET AL
Methanol dialysance in Case 9 was determined on blood
obtained from the arterial inflow and venous outflow from the
dialyzer at 30,80, 90, 120, 180, 240, 380 and 480 minutes.
Blood flow was calculated by duplicate measurements of
bubble transit time over a measured distance, repeated at the
time of each blood sampling. The dialysance was calculated
by the standard formula D = Q(A - V)/A - B where Q is
blood flow in ml/min, A is the serum methanol concentration
on the arterial side of the dialyzer in mg/dl, V is the serum
methanol concentration on the venous side of the dialyzer
in mg/dl, B is the dialysate concentration of methanol in
mg/dl. In a single pass dialysate delivery system, B is negli-
gible in compa&on to A.
CASE REPORTS
Case 1. A 30 year old man ingested approximately 8 ounces
of methanol in a suicidal attempt. He was found unconscious
5 hours later and was taken to a local hospital where he
suffered cardiac arrest. The arterial blood pH was 8.99, the
carbon dioxide tension (pCO*) 54 mm Hg and the bicarbonate
12.5 meq/liter. He was resuscitated and given sodium bi-
carbonate and hydrocortisone hemisuccinate He was
transferred to the Royal Victoria Hospital and hemodialysis
was started 12 hours after the ingestion of methanol. The
patient was comatose with a blood pressure of 100/80 mm
Hg, the pulse rate was 130/min and rectal temperature 38%
Cornea1 and deep tendon reflexes were absent, the pupils
were dilated and unreactive, and the fundi were normal The
hemoglobin level and white blood cell count were within
normal limits. The arterial blood pH was 7.29, pCO:! 13 mm
Hg and bicarbonate 7 mEq/liter. The serum urea nitrogen was
37 mg/dl and the serum creatinine 1.8 mg/dl. The blood
methanol level before dialysis was 580 mg/dl The patient
was dialyzed for 6 hours but remained unconscious After
dialysis the blood methanol level was 180 mg/dl, arterial
blood pH 7.42, pCO:! 31 mm Hg and bicarbonate 20 meq/liter.
Two hours after dialysis, the patient suffered a cardiac arrest.
He was resuscitated, and the blood pressure was maintained
at 100/80 mm Hg with a noradrenaline infusion, but he be-
came oliguric. Twenty hours after the first dialysis, another
8 hour hemodialysis was performed. Two hours after he-
modialysis, pulmonary edema and hypotension developed,
and the patient died 2 hours later. Postmortem examination
revealed marked cerebral edema with extensive bilateral
cerebellar tonsillar herniation. The lungs showed pulmonary
edema and bronchopneumonia, and the liver showed mod-
erate fatty degeneration.
Case 2. A 43 year old man was found unconscious with an
empty bottle of windshield washer fluid beside him Gastric
lavage was performed at a local hospital and he was trans-
ferred to the Royal Victoria Hospital where hemodialysis was
started 4 hours after the estimated time of methanol ingestion.
The blood pressure was 120140 mm Hg, the pulse rate
96/min and the temperature 37%. The cornea1 reflexes were
sluggish, the pupils reacted to light, and fundi showed hy-
peremic optic discs. The deep tendon reflexes were dimin-
ished. The arterial blood pH was 7.32, the pCO* 40 mm Hg
and the bicarbonate 21 meq/liter. The hemoglobin level was
12 5 g/dl and the white blood cell count 9,800/mm3. Fol-
750 May 1976 The American Journal of Medicine Volume 64
lowing the administration of 70 ml ethanol and 89 meq sodium
bicarbonate intravenously, an infusion of 5 per cent ethanol
was started. Assisted ventilation was required. The methanol
value before dialysis was 570 mg/dl. During hemodialysis,
the patient became hypotensive and suffered a cardiac arrest,
but he was resusciated. A noradrenaline infusion was started,
and dialysis was continued for 4 hours. During dialysis, the
patient became responsive to verbal stimuli. Hemodialysis
was performed daily for four days to further decrease the
serum methanol level and for the complicating acute renal
failure, as evidenced by an increase in serum creatinine
values from 0.9 rng/dl to IO mg/dl. The diuretic phase started
on the seventh hospital day, and the serum creatinine value
returned to normal. Vision in the left eye was markedly de-
creased. Initially, there was only light perception in that eye,
but vision improved until he could count fingers at 3 feet.
During his hospitalization he experienced abdominal pain
associated with an increase in serum amylase to 1.2 12 IU/dl
and bilirubin to 2.8 mg/dl. He was discharged after 27 days
of hospitalization.
Case 3. This 51 year old woman accidentally ingested 4
ounces of methanol-containing fluid. She presented to the
Royal Victoria Hospital, the following day complaining of
dizziness, headache and nausea. There was no abdominal
pain, blurring of vision or dyspnea. Physical examination,
including funduscopic examination, visual fields and acuity,
disclosed no abnormalities. Urinalysis, chest roentgenogram,
hemoglobin value, white blood cell count and electrolytes
were within normal limits. The arterial blood pH was 7.30,
pCOn 30 mm Hg and bicarbonate 14 meq/liter. The blood
methanol level was 53 mg/dl. Sodium bicarbonate and eth-
anol were given intravenously; 24 hours after methanol in-
gestion, hemodialysis was started and continued for 4 hours.
The methanol level after dialysis was 38 mg/dl, and intra-
venous ethanol therapy was continued until the methanol was
undetectable in the blood. The patient was discharged after
four days having fully recovered.
Case 4. This 48 year old woman accidentally ingested ap-
proximately 4 ounces of methanol-containing fluid. The next
morning she presented at the Royal Victoria Hospital com-
plaining of slurred speech. She had no nausea, vomiting,
abdominal pain or visual problems. Physical examination
disclosed no abnormalities except for the fundi which showed
slight hyperemia of the optic discs. The urinalysis, hemoglobin
level and white blood cell count were within normal limits.
The arterial blood pH was 7.28, pCOp 23 mm Hg and bicar-
bonate 13 meq/liter. The blood methanol level was 58 mg/dl.
The patient was initially treated with intravenously adminis-
tered sodium bicarbonate and ethanol. and then, 24 hours
after methanol ingestion, dialysis for 4 hours. After dialysis,
the administration of ethanol was continued until methanol
was undetectable in the blood. She left the hospital four days
later having fully recovered.
Case 5. This 15 year old boy drank an unknown quantity of
methanol about 24 hours prior to admission. He felt well until
12 hours after ingestion, when he experienced severe nausea
and vomiting and was brought to the Royal Victoria Hospital.
The blood pressure was 140/80 mm Hg, pulse rate lOO/min,
respirations 28/min and temperature 37’C. He responded

to painful stimuli and inappropriately to verbal commands.
The fundi, deep tendon reflexes and pupillary reflexes were
normal. The arterial blood pH was 7.15, pCOz 13 mm Hg and
bicarbonate 4 meq/liter. Urinalysis was normal, as were the
hemoglobin level, white blood cell count, serum urea nitrogen
and serum creatinine values. The blood methanol level before
dialysis was 74 mg/dl. Emergency treatment consisted of the
intravenous administration of 600 meq of sodium bicarbonate
and ethanol. Hemodialysis was started 24 hours after meth-
anol ingestion. After 6 hours of hemodialysis, the blood
methanol level was 16 mg/dl, arterial blood pH 7.46, bicar-
bonate 14 meq/liter and pCOz 21 mm Hg. The intravenous
administration of ethanol and bicarbonate was continued until
methanol was not detectable in the blood. The patient was
discharged six days later having fully recovered.
Case 6. A 42 year old male prison inmate was admitted to
Queen Mary Veteran’s Hospital, Montreal, 38 hours after the
ingestion of 6 ounces of windshield cleaning fluid containing
90 to 95 per cent methanol. Vision had become blurred and
green within 24 hours of ingestion. Six months previously,
presbyopia and anisotropia had been diagnosed and visual
acuity documented at 20/300 in the right eye and 20/20 in
the left. On admission, the blood was 130/70 mm Hg, res-
pirations 2O/min, temperature 37’C and pulse rate 88/min.
The pupils were dilated, equal and reacted sluggishly to light.
He was able to count fingers at 4 feet. There were bilaterally
large central scotomas and the disc margins were blurred.
The blood methanol concentration was 25 mg/dl, arterial
blood pH 7.41, pC02 16 mm Hg and bicarbonate 10 meq/liter.
One ounce of rye whisky was administered hourly and he
received 100 meq/sodium bicarbonate intravenously. Forty
hours after methanol ingestion, hemodialysis was started and
continued for 4 hours. The blood methanol value after dialysis
was 12 mg/dl, arterial blood pH 7.50 and bicarbonate 23
meq/liter. Vision improved considerably. Two months later
he continued to have bilateral central scotomas. Vision was
20/300 on the right and 20/30 on the left.
Case 7. A 38 year old male prison inmate was admitted to
Queen Mary Veteran’s Hospital, Montreal. Thirty-eight hours
prior to admission, the patient started to ingest windshield
cleaner fluid containing methanol. Approximately 7 ounces
were ingested in the first 18 hours, and 8 ounces were con-
sumed in the subsequent 20 hours. On the day of admission,
he experienced weakness, photophobla, “spots” before his
eyes and blurred vision. He was somnolent and had Kussmaul
respiration. The blood pressure was 140/ 110 mm Hg, pulse
rate/min 80 and temperature 37’C. His speech was slurred.
Pupillary reflexes, visual fields and the optic fundi were
normal. The blood methanol level was 102 mg/di, arterial
blood pH 7.16, pCOn 13 mm Hg and bicarbonate 5 meq/llter.
Intravenous sodium bicarbonate and oral rye whiskey, 1
ounce hourly, were given. Hemodialysis was commenced
within 3 hours of admission (40 hours after methanol inges-
tion) and continued for 5 hours. The arterial blood pH after
dialysis was 7.49, pC02 25 mm Hg, bicarbonate 18 meq/liter
and blood methanol 11.6 mgldl. Vision began to improve after
2 hours of hemodialysis and approached normal by the end
of dialysis. Ethanol therapy was continued for another 12
hours. Visual fields and fundi were normal 15 hours after di-
May 1978
HEWDIALYSIS FOR METHANOL INTOXICATION-GOWA ET AL.
alysis, and corrected vision in each eye was 20125. Seven-
teen days later, corrected vision was 20130 in each eye.
Case 6. In a 45 year old man weakness, dyspnea, nausea,
vomiting, epigastric pain and visual impairment developed
three days after the ingestion of 2 to 3 ounces of methanol.
During the next 24 hours, vision further deteriorated and he
presented to a local hospital. The clinical diagnosis of
methanol poisoning was made and he was transferred to St.
John’s General Hospital for hemrxfiilysis, which commenced
100 hours after methanol ingestion. His pupils were dilated
and unresponsive to light; there was considerable retinal
edema and edema of the optic nerves. Arterial blood pH
before transfer was 7.22, pCO* 20 mm Hg and bicarbonate
8 meq/liter. He was treated with 300 meq sodium bicarbonate
and dexamethasone therapy was started. The blood methanol
level was only 3 mg/dl, but he appeared to have over 20
meqlliter of unidentified anions (anion gap 35 meq/liter),
some of which were presumably metabolites of methanol.
A drinking companion, who ingested considerably more
methanol than this patient, had died 24 hours previously and
was found to have a blood methanol level of 3 18 mg/dl. After
5 hours of hemodialysis, the arterial blood pH was 7.38, bi-
carbonate 17 meq/liter and the anion gap had been reduced
to 21 meqlliter. After dialysis, the patient was given predni-
sone, 100 mg/day, which was continued for three weeks; the
dose was then tapered and discontinued. Ten days later, vi-
sion was 20/160 in each eye, but when seen three months
and 12 months later, he had only light perception.
Case 9. This 48 year old man with a history of alcohol abuse
had ingested an unknown quantity of windshield washer fluid
24 hours prior to admission to the St. John’s General Hospital.
Twelve hours prior to admission, he had been admitted to
another hospital in a state of mental confusion. The arterial
blood values were pH 6.88, pCOn 17.3, mm Hg, and sodium
bicarbonate 4 meq/liter. He was given a total of 700 meq
sodium bicarbonate intravenously. Eight hours before ad-
mission he had a respiratory arrest. He was promptly intu-
bated and given ventilatoty support. Three grand mal seizures
were controlled with diazepam. On admission to the St.
John’s General Hospital, he was comatose, with a blood
pressure of 100/70 mm Hg, and a pulse rate of 130/min. The
pupils were dilated and unresponsive. Bilateral papilledema
was present. The deep tendon reflexes were absent. The
arterial blood gases were pH 7.27, pCOn 19 mm Hg, bicar-
bonate 10.0 meq/liter. The serum urea nitrogen and serum
creatinine values were 18 and 1.8 mg/di, respectively. The
hemoglobin value was 16.3 and the white blood cell count
16,300/mm3. The serum methanol level 18 hours after in-
gestion was 370 mg/dl; the serum ethanol was 4 mg/dl. The
anion gap was 37 rneq/liter with a serum lactate value of 8.58
meq/liter. Hemodialysis was commenced immediately, using
femoral vein and artery cannulation, and continued for 12
hours. The methanol level decreased to 20 mg/dl after dial-
ysis. A loading dose of 40 ml ethanol before dialysis and an
infusion of 15 ml of absolute alcohol/hour attained a serum
ethanol level of only 16 to 20 mg/dl. After an additional dose
of 40 ml ethanol and 24 ml ethanol/hour a serum ethanol level
of 100 mg/dl was attained during hemodialysis. No recovery
was apparent, and an isoelectric eiectroencephograph was
The American Journalof Yedlclne Volume 64 751
HEWDIALYSIS FOR METHANOL INTOXICATION-GONDA ET AL.

TABLE I Summary of Clinical and LaboratoryData

Time
from
Inges-
Age tion to Blood Predialysis
(yr) Dlaly- Metha- Arterial Blood Serum
Case and Methanol SiS IlO1 (meq/liter) Anion
No. Sex ingested (hr) Clinical (mg/dl) (miHHg) (mz:er) (mf$ier) Na K Cl Gap Therapy outcome

30, Methanol 12 Comatose 560 729 13 7 150 54 100 43 NaHCO, Died

M containing dialysis
fluid 6 oz 2X6
hours
43, Windshield 4 Comatose 570 7 32 40 21 138 31 88 29 Ethanol (IV) Survrved,
M washer fluid NaHCOs eye
several 02 dialysis dam-
5x4 age
hours
5 1, Methanol-cont- 24 Dizzrness, 53 7 30 30 14 142 3.7 96 32 Ethanol (IV) Survived,
F ainrng fluid headache, NaHCOs normal
4 oz nausea dralysis vision
4 hours
46, Methanol-cont- 24 Slurrrng, 56 7.26 23 13 142 32 100 29 Ethanol (IV) Survived,
F ainrng fluid speech NaHCOs normal
4 oz dialysis vision
4 hours
15, Wtndshield 24 Stuporous 74 715 13 4 138 54 102 32 Ethanol (IV) Survived,
M washer flurd NaHC03 normal
unknown dralysrs visron
quantity 6 hours
42, Windshield 40 Greenish, 25 741 16 10 140 33 98 32 Whiskey Survived,
M washer flurd blurred NaHCOs eye
6 oz (90-95 vision dialysis dam-
per cent 4 hours age
methanol)
36, Windshield 40 Profound 102 7 16 13 5 140 47 98 37 Whiskey Survived,
M washer fluid weakness NaHCOs normal
15 oz photophobra dialysis
(90-95 per 5 hours
cent
methanol)
45, Methanol 2-3 100 Weakness, 3 7 22 20 a 134 46 91 35 NaHCOs Survived,
M oz vomiting, dialysis eye
abdominal 5 hours dam-
pain age
46, Windshield 24 Confusron 370 688 22 4 142 5 2 101 37 Ethanol Died
M washer fluid progressing NaHCOs
unknown coma dialysis
quantity 12 hours
Note: NaHCOs = sodrum bicarbonate; Na = sodium; K = potassium; Cl = chlorrde

recorded 24 and 48 hours after hemodialysis at a time when
neither ethanol normethanolwas detectablein the blood. The
patient died 48 hours after hemodialysis Autopsy revealed
marked cerebral edema.
RESULTS
Present Series (Tables I and II). Seven patients were
male and two female with an age range of 15 to 48
years. Two died and three of the seven survivors had
permanent visual defects. All but two patients who did
not receive ethanol (Cases 1 and 8) were treated with
ethanol, sodium bicarbonate and hemodialysis. One
patient (Case 8) did not receive ethanol because the
methanol had been almost entirely metabolized. The
interval between ingestion and dialysis ranged from 4
hours to 100 hours: it was 12 and 24 hours in the pa-
tients who died.
The amount of methanol ingested and resultant blood
levels varied considerably. Ingestion of approximately
6 ounces of methanol-containing fluid caused death in
the first patient whereas the amount ingested by one
patient (Case 9) was unknown. The amount of metha-
nol-containing fluid ingested by the seven survivors was
known in five cases and varied from 2 to 15 ounces.
Two patients were very mildly symptomatic with blood
methanol levels of 53 and 56 mg/dl, respectively, one

752 May 1978 The American Journal of Medicine Volume 84

 HEMODlALYSlS FOR METHANOL INTOXICATION-GONDA ET AL

TABLE II Visual Status

CM8 BeforeDlalysls Result

Absent cornea1 and pupillary reflexes; fundi normal Died

Normal puplllary reflexes; hyperemia of discs Normal right eye; permanent damage left eye
0.0. 20/20, OS. 20120; normal pupil&y reflexes: fundi normal Normal
Some blurring of vision; O.D. 20120, 0 S. 20/20, normal pupillary Normal
reflexes; minimal hyperemia of discs
5 0.0. 20/20, OS. 20120; normal pupillary reflexes; fundi normal Normal
6 Six months before admission 0.0. 20/200, OS 20/20; pupils Permanent bilateral central scotomas 2 mo later
reacted sluggishly to light: bilateral large central scotomas, pale OD 2OI300.0 S 20130
optic discs; counted fingers at 4 ft
7 Slurred vision; normal pupillary reflexes; normal visual field Normal 0 0 20/30, O.S. 20/30
6 Blind, fixes dilated pupils; edema of retina and optic nerve No hght vision 6 days later; 0 D. 201160, 0 S
201160; 10 days later after onset; only able to
distinguish light and shadows after 3 mo
9 Absent cornea1 and pupillary reflexes; bilateral papilledema Died

was stuporous with a concentration of 74 mg/dl, and
three were conscious but symptomatic, with levels of
25, 102, 3 mg/dl. Three patients were comatose with
blood levels of 370, 560, 570 mg/dl; the first two
died.
All patients had metabolic acidosis before dialysis,
and eight of nine had reduced arterial blood pH values
(Table I). There was poor correlation between the blood
methanol value and the initial degree of metabolic ac-
idosis. One patient (Case 2) had a blood methanol level
before dialysis of 570 mg/dl with an arterial blood pH
of 7.32 and a bicarbonate of 20 meq/liter, but the in-
terval was only 4 hours between the time of ingestion
and dialysis; subsequently severe metabolic acidosis
developed. One patient (Case 8) had a blood level of 3
mg/dl with a pH of 7.22 and a bicarbonate of 8 meq/
liter, 100 hours after methanol ingestion. The initial
anion gap was increased in all patients, ranging from
29 to 43 meq/liter.
The visual status before and after therapy is sum-
marized in Table II. In the three patients (Cases, 2, 6 and
8) in whom permanent visual defects occurred, initial
values measured 4, 40 and 100 hours after methanol
ingestion were for blood methanol 570, 25 and 3 mg/dl;
for arterial blood pH 7.32, 7.41 and 7.22, and for the
anion gap 29,32 and 35 meq/liter. These values do not
differ from the values found in the patients who recov-
ered without loss of vision (Table I).
The dialysance of methanol for the CDAK model 5
hollow fiber dialyzer ranged from 56 to 200 ml/min over
a blood flow rate of 72 to 250 ml/min (Table Ill). The
dialysate flow was 400 to 600 ml/min. The dialysance
increased with an increased blood flow rate.
COMMENTS
Detailed reviews of the metabolism and toxicity of
methanol have been published [ 17- 191. Intoxication
can occur with ingestion, inhalation of methanol vapour
or by absorption through the skin. Animal experiments
indicate that a variable (25 to 75 per cent) proportion
of methanol is eliminated unchanged in expired air [ 171
whereas approximately 3 to 10 per cent of an admin-
istered dose is excreted unchanged by the kidney
[ 20,2 11. Methanol is oxidized to formaldehyde and then
quickly oxidized to formic acid both in vitro and in vivo.
Although a catalase pathway has been proposed, most
evidence indicates that oxidation by alcohol dehydro-
genase is the primary route of metabolism [ 181. The
rate of oxidation of methanol appears to be much slower

TABLE Ill Methanol Dialysance (Case 9)

lime from Serum Methanol

Start of Arterial Venous
Hemodlalvsls Blood Flow inllow InflOW A-V Pialysance
(mln)’ (mllmln) Wdl) (m@W (mW) (mllmin)

30 100 250 34 216 86 4

60 72 242 55 187 55 7
90 100 212 45 167 78.8
120 130 187 43 144 100 1
160 250 166 37 129 194 3
240 250 112 33 79 176 3
360 250 54 16 38 175.3
460 250 40 8 32 200 0
-

May 1978 The American Journal of Medicine Volume 64 753

HEMODIALYSIS FOR METHANOL INTOXICATION-GONDA ET AL
than that of ethanol [21]. Studies with C-14-labelled
methanol indicate that highest concentrations occur in
the liver, kidneys and gastrointestinal tract with com-
paratively small concentrations in the brain, muscle and
adipose tissue [21].
Bartlett [21] concluded, from his experience with
labelled methanol in rats, that oxidation proceeded at
a constant rate independent of the concentration of
methanol in the blood, but clinical experience indicates
that symptoms appear earlier in patients who have in-
gested greater amounts of methanol [I]. The sponta-
neous blood methanol half-life varies from 28 to 82
hours in dogs [22].
During methanol poisoning in man, the concentra-
tions of methanol and formic acid in the blood are quite
variable. Lund [23], in 5 fatal cases of methanol poi-
soning, found blood methanol values ranging from 74
to 110 mg/dl and blood formic acid values from 9 to 68
mg/dl. The maximum excretion of formic acid occured
not later than the second or third day after methanol
ingestion [23]. Although in most reported fatal cases
blood methanol levels were greater than 100 mg/dl,
deaths have occurred with concentrations as low as
27.5 mg/dl [2] and this may be related to the time
elapsed from ingestion. In most fatal cases, blood for-
mic acid levels were greater than 10 mg/dl [23] but
fatalities have occurred with values as low as 5.7 mg/dl
[24]. Van Slyke and Palmer [25] noted the excretion
of unidentified organic acids following methanol poi-
soning in addition to an increase in urinary lactic and
formic acid excretion. Thus, the mechanism of the se-
vere metabolic acidosis is not entirely explained by the
production of formic acids. Lactic acid and other un-
identified acids may play a role. The serum lactate value
was increased to 8.58 meq/liter in Case 9, although the
prior respiratory arrest and convulsions may have
contributed to this increase.
Studies in nonprimate animals have added little to
knowledge of methanol toxicity in man. In nonprimates,
the toxicity of methanol is that due to the general an-
esthetic effect. Lethal doses of methanol do not cause
severe acidosis in nonprimates and, usually, no clear
impairment of vision is seen [ 171. However, Marc-
Aurele and Schreiner [22] noted blindness in their se-
verely methanol-intoxicated dogs. Most of the data re-
garding methanol toxicity in man has been obtained
from clinical studies on people and groups of people
who had ingested methanol either accidentally or with
suicidal intent.
The clinical components of the syndrome in man
following methanol ingestion are well known, yet there
is great variability. Bennett and associates [ 1] found that
the lowest fatal dose to be 15 ml of 40 per cent meth-
anol; however, survival had occurred after ingestion of
500 ml. The generally accepted potentially lethal dose
is 30 ml [ 151. The latent period for symptoms ranges
754 May 1978 The American Journal of Medicine Volume 64
from 40 minutes to 72 hours [ 11. There was little rela-
tionship between the dose and either the length of the
latent period or severity of the symptoms. Neither was
there a relationship between the length of the latent
period and the severity of symptoms. Mortality was
found to correlate best with the degree of acidosis [ 11.
The mortality rate for the 323 patients in the 1952 At-
lanta methanol poisoning epidemic was 6.2 per cent
[ 11. The mortality rate was 19 per cent for the 115
patients with values for C02-combining power <20
meq/liter, and 50 per cent for the 30 with COz-com-
bining power values < 10 meq/liter.
Visual complications have also been reported to
correlate with acidosis. Bennett and associates [l]
found that all 115 patients with methanol intoxication
who were acidotic on admission had at least temporary
impairment of vision whereas only 50 per cent of those
without acidosis had visual complaints [ 11. Roe [27]
stated that the visual symptoms will appear only in the
presence of systemic acidemia whereas Beaudry and
associates [lo] concluded that the severity of visual
damage was related to the duration and severity of the
acidosis. Potts [28] studied eight Rhesus monkeys
given double the minimal lethal dose of methanol. Bi-
carbonate administration prevented acidosis; four
monkeys survived, three with retinal edema (transient
in two). Formaldehyde has been shown, in vitro using
ox retinas, to be a potent inhibitor of anaerobic glycol-
ysis and to enhance aerobic glycolysis [29]. Formic
acid was less toxic than formaldehyde and methanol
less toxic again [29].
Autopsy findings in man include cerebral edema and
hemorrhagic pancreatitis [ 11. Fatty infiltration of the
liver is frequently present [ 11. The nuclei of the ganglion
cells of the retina are pushed to the extreme periphery
and the dendrites are difficult to see even with silver
stains [ 171. Orthner [30] described symmetric pu-
tamenal necrosis in 41 of 124 patients with methanol
poisoning, and clinical findings in a 13 year old girl who
had survived severe methanol poisoning were consis-
tent with putamenal damage [31].
Control of acidosis with sodium bicarbonate is vital.
In 1920, Harrop and Benedict [32] demonstrated that
acidosis occurs with methanol poisoning and suggested
treatment with alkali. Of 30 patients treated with alkali
by Branch and Tonning [33] 25 survived and only one
had a visual defect at follow up four months later.
Eighty-two patients with varying degrees of acidosis
were treated with sodium bicarbonate by Roe in 1946:
27 died and 20 had permanent amblyopia [24]. He
found that the severity of the acidosis was closely re-
lated to amblyopia and mortality. Tonning, Brooksand
Harlow used alkali in the therapy of 49 patients in 1955
[34] combined with 5 per cent ethanol in nine: all 49
survived without visual impairment. In contrast, seven
of 25 severely acidotic patients described by Bennett
 HEh4ODlALYSlS FOR h4ETtfANOL INTOXICATION--GONDA ET AL

TABLE IV Patients with Methanol Poisoning Treated with Hemodialysis

No. Permanent
Of OutcOme vishl Viwal
Reference Patients Survived Died Unknown Normal Damage

Austin et al. 1961 [3] 1 1 1

Wieth, Jorgensen 1961 [4] 1 1
Shinaberger 1961 [5] 1 1 1
Felts et al. 1962 [6] 1 1 1
Cowan 1964 [7] 1 1 1
Erlanson et al. 1965 [2] 6 1 3 2 1
Pfister et al. 1966 [8] 1 1 1
Cerny et al 1966 [9] 1 1 7
Maher, Schrerner 1967 [ 1 l] 2 2 7
Beaudry et al. 1967 [lo] 3 3 1 2
Gloss, Solberg 1970 [ 121 1 1 1
Humphrey 1974 [ 131 1 1 1
Keyvan-Larijarni et al 1977 [ 141 8 5 1 4 1
Present series 1977 9 7 2 4 3

Total 35 24 7 4 15 8

and associates [l] died, despite correction of serum
bicarbonate levels by intensive alkali therapy. Five of
the 18 survivors had permanent visual damage.
Roe noted that patients who drank ethanol with
methanol had less severe methanol intoxication and
suggested that use of ethanol in addition to alkali therapy
[24]. Bartlett demonstrated with C14-labeled methanol,
that an ethanol concentration of 46 mg/di caused a 72
per cent inhibition of the oxidation of methanol to
formaldehyde and formic acid in rat liver slices [35].
In two reports in which combined alkali-ethanol therapy
was used, ail 33 patients survived and only two had
permanent visual impairment [36,37]. Ethanol can be
given either orally or intravenously, and it has been
recommended that the blood ethanol concentration be
kept around 100 mg/di [ 21. To attain this level in a 70
kg man, a loading dose of 50 g should be followed by
the infusion or ingestion of 10 to 12 g/hour [2].
As cerebral edema is frequently found at autopsy and
is known to cause respiratory arrest, the use of corti-
costeroids in large doses seems reasonable, although
its value is unsubstantiated.
The small molecular size, distribution in total body
water and the time lag between the ingestion of meth-
anol and its metabolism to more toxic and also diaiy-
zabie substances [2] indicates that early dialysis would
be an appropriate form of therapy for methanol poi-
soning.
in 1960 Steinbaugh [38] used peritoneal dialysis in
three patients with methanol intoxication. Two patients
survived but became blind; the third died during dialysis.
Kane and associates [37] treated four patients with
peritoneal dialysis, ethanol and alkali. Three of four
survived without impairment. In one patient, 66 g of
methanol (equivalent to 80 ml absolute methanol) was
removed in 36 hours. Methanol diaiysance with peri-
toneai dialysis was found to be about one eighth of that
with hemodialysis [39]. Although less efficient than
hemodialysis, it should be used with alkali and ethanol
therapy when hemodialysis is not available.
Marc-Aurele and Schreiner [22] demonstrated an
“in viva” diaiysance in dogs of 75 to 191 ml/min with
blood flow rate dependence using a twin coil artificial
kidney and found that dialysis increased the rate of re-
moval of methanol from blood by a factor of 16 to 22.
Setter and associates [39] reported a methanol di-
alysance of 150 to 200 ml/min at blood flows of 200 to
250 ml/min using a twin coil artificial kidney.
The first report of treatment of methanol intoxication
in man by hemodialysis was published by Austin, Lape
and Burham [3] in 1961. Since then, 35 patients (in-
cluding ours) have been treated for methanol intoxica-
tion by hemodialysis and reported on in the English
language literature (Table IV) [ 2- 141. Considering the
31 patients treated with hemodiaiysis for whom suffi-
cient data are available for analysis, seven died and 24
survived, but eight survivors had permanent visual de-
fects (Table IV).
Blood methanol values were reported in 27 patients
and ranged from 3 mg/dl to 570 mg/dl (mean 142
mg/dl) and bicarbonate values ranged from 3 to 21
meq/iiter (mean 10 meq/iiter). The time from ingestion
to h,emodialysis, recorded for 25 patients, varied from
4 to 100 hours (mean 36 hours).
Values for blood methanol and bicarbonate on .ad-
mission to the hospital, and the time interval between
Ingestion and institution of hemodialysis for (1) patients
who died, (2) survivors with permanent visual defects
and (3) survivors without visual damage, are found in
Table V. Mean blood methanol values are 200, 150 and
109 mg/dl for the 3 groups, and the mean time intervals
from ingestion to hemodialysis were 37, 43 and 28

May 1978 The American Journal of Medicine Volume 64 755

HEMODIALYSIS FOR METHANOL INTOXICATION-GONDA ET AL

TABLE V Outcome and Biochemical Data for Methanol lntoxlcated Patients Treated by Hemodialysis (HD)

Death Survival with Visual Defect Survival with Normal Vision

Pre-HD Pre-HD Pre-HD Pre-HD PresHD Pre-HD
Blood Serum Ingestion Blood Serum Ingestion Blood Serum Ingestion
Ref- Methanol HCOs to HD Ref- Methanol HCOs to HD Ref- Methanol HCOs to HD
erence (mg/dl) (meq/llter) (hr) erence (mg/dl) (mgldi) (hr) erence (mgldl) (meqlliter) (hr)

[41 146 61 30 (31 + 9.4 53 tz 2o 51 48

1:; 28
27 110
8o 52
53 [lo] 63
68 30
73 ’7 171 40
360 14.0
70 30
18
121 ss 14 0 53 t:z + 49 24 l9 83 50
jl41 186 5j 35 [I41 171 13 0 38 1:; 105 16 0 10
l 560 70 12 * 570 21 0 4 [lo] 45 18 2 10
l 370 4.0 24 * 25 10 0 40 ;::I 185 40 27
l 3 80 100 178 55 27

t::; 198
g6 6 O
55 28
38
* 53 140 24
1 56 13 0 24
. 74 40 24
(I 102 13 0 40

Mean 200 37 150 96 109

(27-560) (48184, (12-53) (3-570) (3-21) (4-::o, (19-360) (49 :8) (lO’“,O,
l This report

hours, respectively, with considerable overlap between
groups in each instance. The initial serum bicarbonate
values were similar in all three groups Thus, there
appears to be no clear cut-off in the relationship be-
tween survival and the blood methanol level on ad-
mission, the degree of acidosis or the time to initiation
of therapy. This is true for blood methanol levels even
when zero time values are calculated using an average
rate of disappearance based on a blood methanol half
life of 28 to 62 hours [22].
There is even less correlation between these pa-
rameters and impaired vision. Nevertheless, it is clear
that irreversible brain damage can occur within 12 to
24 hours with massive doses and that subsequent
correction of acidosis, ethanol infusion and hemodial-
ysis can be ineffectual (Case 1 and 9). In contrast, one
patient (Case 2) in our series had a blood methanol
value of 570 mg/dl but survived with visual impairment.
The very short period, which had elapsed (4 hours)
before hemodialysis was started, may have prevented
significant metabolism to toxic metabolites. The critical
time before which dialysis must be instituted may vary
inversely with the dose ingested.
Keyvan-Larijarni and Tannenberg [ 141 described six
patients with methanol intoxication who presented 24
hours after ingestion. Three were treated promptly with
hemodialysis, ethanol and alkali; all three recovered.
Three others were treated initially with peritoneal dial-
ysis, ethanol, alkali and later with hemodialysis. One
patient died and another became permanently blind.
This report suggests that prompt hemodialysis com-
bined with ethanol and alkali therapy is important.
Rapid falls in blood methanol levels during hemodi-
alysis have been reported [2,4,6-8,10,14], and con-
firmation is provided in this study (Table Ill). However,
as the rate of decrease in blood levels is affected by
ethanol administration, methanol metabolism and renal
clearance, it is difficult to use changes in blood levels
to quantitate the amount of methanol removed by a
particular dialyzer. Gibson and associates [40] state
that dialyzer clearances based on the amount recovered
in the dialysate are more accurate than measurement
of dialysance. If one applied the clearance formula used
by Gibson and associates [40] to the data of Erlanson
and associates [2] the methanol clearances for four
patients averaged 90.6 ml/min at a blood flow rate
varying between 150 and 300 ml/min. Application to
the data of Marc-Aurele and Schreiner [22] using a
twin-coil dialyzer yields methanol clearances of 41.4
and 47.8 ml/min. This represented a minimum clear-
ance as no correction could be made for methanol
evaporated from the surface of the dialysate. Marc-
Aurele and Schreiner [22] calculated the dialysance
for methanol by the twin coil kidney in vitro and found
that dialysance increased with blood flow rate. The di-
alysance values were 75, 140, 160 ml/min at blood flow
rates of 100, 250, 300 ml/min. Setter and associates
[39] found that dialysance of methanol by the twin coil
artificial kidney increased with blood flow rate and re-
ported values of 110, 200 and 300 ml/min at blood flow
rates of 150, 200 and 300 ml/min. The P-layer Kiil had
clearance values 90 to 125 ml/min at blood flow rates
200 to 300 ml/min [39].
Clearance measurements for methanol using a large

756 May 1976 The American Journal of Medlclne Volume 64


surface area dialyzer, such as the 2.5 m2 CDAK model
5, have not been reported. In our ninth patient the di-
alysance for methanol increased with increasing blood
flow rates and reached a mean value of 196 ml/min at
250 ml/min (Table Ill).
Although treatment with sodium bicarbonate and
ethanol may improve the prognosis of patients with
methanol poisoning [36,37], rapid removal of methanol
and its dialyzable products [2] is advisable because
complications can occur when acidosis is controlled,
severe acidosis can recur after an initial period of
control, and hospitalization may be shortened with
hemodialysis [ 141.
Exact indications for dialysis in methanol poisoning
are difficult to define as the outcome, particularly for
vision, is not easy to predict on initial evaluation.
Schreiner [41] suggested that hemodialysis be insti-
tuted following methanol ingestion if the methanol blood
levels are above 100 mg/dl, or if severe acidosis or
visual impairment was present. We recommend he-
modialysis in the presence of any of the following: a
blood methanol level exceeding 50 mg/dl, metabolic
acidosis of any degree, mental visual or funduscopic
abnormality attributable to methanol or if there has been
consumption exceeding 30 ml methanol. These indi-
cations will probably require revision as more experi-
ence is reported. The artificial kidney with the largest
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surface area available is preferred and the most rapid
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Our experience in our ninth patient using the CDAK
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758 May 1978 The American Journal of Medlclne Volume 64