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Citation: Alqurashi, G.I.; Alqurashi,
F.S.; Alhusayni, K.M.; Falemban,
A.H.; Alhindi, Y.Z.; Alsanosi, S.M.;
Alzahrani, A.R.; Al-Ghamdi, S.S.;
Ayoub, N. Case Reports Study on
Methanol Poisoning in King Abdul
Aziz Specialist Hospital, Taif, Saudi
Arabia. J. Clin. Med. 2023,12, 4282.
https://doi.org/10.3390/
jcm12134282
Academic Editor: Umberto Aguglia
Received: 5 February 2023
Revised: 28 May 2023
Accepted: 19 June 2023
Published: 26 June 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Journal of
Clinical Medicine
Article
Case Reports Study on Methanol Poisoning in King Abdul Aziz
Specialist Hospital, Taif, Saudi Arabia
Ghadi I. Alqurashi 1,2, Fahad S. Alqurashi 1, Khalid M. Alhusayni 1, Alaa H. Falemban 2,3, Yosra Z. Alhindi 3,
Safaa M. Alsanosi 3, Abdullah R. Alzahrani 2,3 , Saeed S. Al-Ghamdi 2,3 and Nahla Ayoub 2,3,*
1Pharmacy Department, King Abdulaziz Hospital, Taif 26521, Saudi Arabia
2Saudi Toxicology Society, Umm Al-Qura University (UQU), Makkah 21955, Saudi Arabia
3Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University (UQU),
Makkah 21955, Saudi Arabia
*Correspondence: naayoub@uqu.edu.sa; Tel.: +966-5-3219-0083
Abstract:
Methanol poisoning is a challenging issue due to its inducing acute multiple organ failures,
and especially due to a lack of preparedness, available antidotes, and management protocols. The
current study presents six cases of methanol poisoning that attended the emergency department
of King Abdul Aziz Specialist Hospital, Taif, Saudi Arabia, between March and November 2022.
All of the patients suffered from severe metabolic acidosis and visual impairment following the
ingestion of homemade alcoholic beverages and colonia. Three patients were comatose, suffered
from post-cardiac pulmonary arrest, and, finally, died, while the other three were non-comatose and
discharged from the ICU after improvement. Management was based on clinical symptoms and
other laboratory findings due to a shortage of methanol level measurement resources. The antidote,
fomepizole, was not given to all of the cases due to its deficiency, and ethanol was given only to
one patient due to difficulties in administering it without monitoring its concentration. Methanol
poisoning and its outbreak provide insights into the dangers of hazardous homemade alcohol and
other pharmaceutical preparations that might be adulterated with methanol, particularly to the
shortage of suitable diagnostic testing and antidotes in addition to poor resources for management of
intoxicated patients in some regions of Saudi Arabia.
Keywords:
methanol poisoning; case reports; metabolic acidosis; visual loss; multi-organ failures;
Saudi Arabia
1. Introduction
Methanol (colonial spirit) belongs to the alkyl alcohols family, which is the simplest
form of this family, and its toxicity occurs through exposure via inhalation, ingestion,
or dermal contact with methanol-containing formulations. Methanol is considered most
dangerous when ingested. Unfortunately, only 10 mL of pure methanol can be lethal or
can cause life-threatening poisoning and permanent vision loss [
1
]. Methanol is similar
to ethanol and is used for many industrial purposes such as airplane fuel, antifreeze,
and wiper fluids, in addition to its use as a solvent in cologne, the perfume industry,
and homemade formulations [
2
,
3
]. Ingestion of methanol may occur accidentally, due to
suicide attempts, or adulterated wine [
3
,
4
]. Alcohol dehydrogenase (ADH) and aldehyde
dehydrogenase (ALDH) are the enzymes responsible for the metabolism of methanol. ADH
degrades methanol into formaldehyde, which in turn is converted to the highly toxic formic
acid by the action of ALDH [
5
]. The accumulation of formic acid triggers metabolic acidosis
by its self-deposition and inhibition of mitochondrial cytochrome c in addition to multiple
organ failures [
6
]. Furthermore, formic acid accumulation in the eye causes blurred vision
and finally visual loss due to the lack of retinal mechanisms of formic acid detoxification [
7
].
It has been reported that death from methanol poisoning may range between 8 and 36% [
8
],
and patients who still survive after acute methanol poisoning showed permanent vision
J. Clin. Med. 2023,12, 4282. https://doi.org/10.3390/jcm12134282 https://www.mdpi.com/journal/jcm
J. Clin. Med. 2023,12, 4282 2 of 11
loss in about 20–40% of cases [
2
,
3
,
9
]. Methanol displays acute toxicity rather than chronic
toxicity, which is manifested by gastrointestinal symptoms, central nervous system (CNS)
suppression, confusion, coma, and cardiopulmonary arrest, in addition to vision loss and
severe metabolic acidosis, the main cause of mortality [
10
,
11
]. Fomepizole or ethanol is the
standard antidote for methanol poisoning, acting as ADH inhibitors, preventing end-organ
damage by inhibiting the formation of formaldehyde and formic acid, in addition to renal
replacement therapy [12].
Many social and cultural factors influence the lack of reporting of methanol poisoning
cases in Saudi Arabia. Some presentations were delayed because patients feared legal
consequences and deferred their visit to a healthcare facility until symptoms worsened and
became unbearable, or until they feared permanent vision loss [11,13].
This study clearly points out the limitations of the treatment options in Saudi Ara-
bia (i.e., availability of ethanol/methanol testing in blood in hospitals and antidotes
(ethanol/fomepizole infusions)), in addition to showing laboratory test limitations and
time constraints. Further, the lack of national treatment guideline protocols and diagnostic
criteria of methanol poisoning result in treatment variation. Herein, we report six cases of
methanol poisoning in the period between March and November 2022 in King Abdul Aziz
Specialist Hospital, Taif, KSA, and discuss the different challenging procedures and issues
facing these cases from the public health perspective.
2. Material and Method
Six middle-aged patients were admitted to the emergency department, King Abdul
Aziz Specialist Hospital, Taif, Saudi Arabia, after alcohol consumption from March 2022 to
November 2022. Ethical approval from the Directorate of Health Affairs, Taif, Research and
Studies Department, IRB registration number with KACST, KSA: HAP-02-T-067, approval
number: 517, date: 12 February 2021 was documented. In this report, the demographic
characteristics, laboratory parameters, clinical symptoms, management procedures, and
outcome of methanol poisoning was recorded for each case. Written informed consent was
obtained from the patients to publish these case reports in accordance with the journal’s
patient consent policy. For patients who were unable to give written consent or deceased, it
was obtained from the patients’ next of kin.
2.1. Cases Presentation
Six methanol poisoning cases were transferred by ambulance to the emergency de-
partment of King Abdul Aziz Specialist Hospital, Taif, KSA. Three of them were admitted
on 16 November 2022 (two Saudi and one Indian). Another three intoxicated patients
were admitted on 4 March 2022 (two Indian, and one Nepalese). The first three patients
were comatose, suffered from severe metabolic acidosis, vision loss, and pulmonary car-
diac arrest. One of them was hypothermic and another one had acute renal failure and
anorexic brain damage. The management of the three comatose intoxicated patients failed
and they died. The other three came in together and were non-comatose, drowsy with
metabolic acidosis, had toxic optic nerve damage, and one of them was feverish. They
were discharged from the hospital after the appropriate management, where they were
administered with the antidote fomepizole and hemodialysis in addition to correcting
their metabolic acidosis with sodium bicarbonate. Detailed histories were taken from the
patients and their companions. All of the cases had failed to buy alcoholic beverages.
Instead, they ingested a homemade alcoholic beverage containing 70% ethanol and colonia.
They drank several glasses of this alcoholic beverage the day before they were referred to
the emergency department. All of the patients were promptly admitted to the intensive
care unit (ICU). The demographic and admission profile data for the six cases are presented
in Table 1, while their vital signs and clinical laboratory parameters data are presented
in Table 2. In addition, the methanol poisoning symptoms and management course data
are presented in Tables 3and 4, respectively. Plasma osmolality is determined mainly by
sodium (Na), its counter ions, and uncharged species such as glucose (GLU) and urea (UN).
J. Clin. Med. 2023,12, 4282 3 of 11
Knowledge of the plasma concentration of these species allows calculation of the plasma
osmolality quite accurately. The difference between the measured osmolality (MO) and cal-
culated osmolality (CO) is known as the osmolar gap (OG). A large positive (>15) osmolar
gap can help to identify the presence in plasma of substances such as ethanol, methanol,
isopropanol, ethylene glycol, propylene glycol, and acetone. The proper interpretation
of the OG also requires knowledge of the anion gap (AG = Na
−
HCO
3−
Cl), the blood
pH, and qualitative testing of the plasma ketone bodies (KETO). When the OG is com-
bined with the blood pH and AG, poisoning with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly elevated OG (>15) is a medical
emergency that requires prompt treatment [
14
]. Based on this, the anion gap (AG) was
calculated from the following equation: AG = (Na
+
+ K
+
)
−
(Cl
−
+ HCO
3−
) in mmol/L,
where a normal range of AG should be 13
±
8 mmol/L [
14
]. The osmolal gap (OG) was
calculated from the following equation: Serum osmolality–calculated osmolality ((2
×
[Na])
+ (glucose, in mg/dL)/18 + (blood urea nitrogen, in mg/dL)/2.8) in Mosmol/kg, where
normal individuals should have a value between 10 and
−
10 [
15
], as illustrated in Table 5.
Further, outcome data for the six cases are presented in Table 6.
Table 1. Demographic and admission profiles for the six cases.
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6
Gender Male Male Male Male Male Male
Age in years 43 26 44 41 32 30
Nationality Saudi Indian Saudi Nepalese Indian Indian
Hospital
admission date
16 November 2022 16 November 2022 16 November 2022
4 March 2022 4 March 2022 4 March 2022
Hospital
duration 10 h 12 h 10 h 5 d 3 d 3 d
Exposure Alcohol history Alcohol history Colonia ingestion
Alcohol
ingestion
(colonia)
Alcohol
ingestion
Alcohol
ingestion
(colonia)
Methanol
poisoning Yes Yes Yes Yes Yes Yes
Methanol level
(mg/dL) NA 275 NA NA NA NA
NA: data not available.
Table 2. Vital signs and clinical laboratory parameters for the six cases.
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6
Pulse (beats/min) 101 80 138 62 96 82
RR (respirations/min) 20 20 22 20 20 20
BP (mm.Hg) 79/64 98/48 170/116 133/90 143/87 145/95
Temp (◦C) 37 37 34.7 36.6 36.6 38.2
SPO2(%) 100 100 99 90 96 95
PCO2(mm.Hg) 45.9 54.2 19 36.4 28 25
Arterial pH 6.56 6.8 7 7.19 7.1 7.1
HCO3(mmol/L) 1.7 1 4 10 11.2 8.5
TLC 18.8 8.47 NA NA NA NA
Hgb (g/dL) 14.8 16 16.4 13 17.1 16
WBC (g/L) 18.8 12.24 11.9 6.34 14.1 17
PLT (g/L) 206 151 342 355 307 389
INR 1.1 NA 1.1 1.14 1.08 NA
AST (U/L) 173 446 48 41 35 19
ALT (U/L) 82 116 81 59 29 12
ALP (U/L) 106 61 109 NA 103 109
Direct bilirubin (mg/dL) 0.16 0.46 0.14 0.2 0.2 0.3
T.protein (g/dL) 5.9 5 NA 6.3 6.6 6.6
Albumin (g/dL) 3.6 2.6 3.7 3.5 3.5 3.6
J. Clin. Med. 2023,12, 4282 4 of 11
Table 2. Cont.
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6
T.bilirubin (mg/dL) 0.2 0.6 0.3 0.7 0.7 0.7
λGT (U/L) 111 155 NA 137 30 58
RBS (mg/dL) 151 207 261 117 (FBS) 64 81
LDH (U/L) 510 NA 250 NA NA NA
Mg (mg/dL) NA 2.55 1.59 NA NA 1.7
Ca (mg/dL) 7.8 9.4 9.1 8.4 5.8 8.6
Na (mmol/L) 142 160 143 139 134 142
K (mmol/L) 4.4 1.4 3.2 3.4 3.2 3.2
Cl (mmol/L) 111 122 109 107 103 113
Osmolality serum (Mosmol/kg) 283.5 312 329 274.85 260.7 283.9
Cr (mg/dL) 1.36 1.38 1.11 0.7 0.73 0.77
Urea (mg/dL) 27.82 27.8 26.2 14.98 34 23.54
NA: data not available. RR: respiratory rate, BP: blood pressure, Temp: temperature, SPO
2
: oxygen saturation,
PCO
2
: partial pressure of carbon dioxide, HCO
3
: bicarbonate, TLC: total leukocyte count, Hgb: hemoglobin,
WBC: white blood cell, PLT: platelet thrombocyte count, INR: international normalized ratio, AST: aspartate
aminotransferase, ALT: alanine transaminase, ALP: alkaline phosphatase,
λ
GT:
λ
glutamyl transferase, RBS:
random blood sugar, LDH: lactate dehydrogenase, Mg: magnesium, Ca: calcium, Na: sodium, K: potassium, Cl:
chloride, Cr: creatinine.
Table 3. Clinical symptoms of methanol poisoning for the six cases.
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6
Eye:
- Pupil Dilated Dilated Dilated
Dilated with
sluggish
response
Dilated Dilated
- Vision Visual loss Non-reactive
to light Lost left eye Toxic optic
nerve damage
Toxic optic
nerve damage
Toxic optic
nerve damage
and blurred
vision
Heart Arrest Arrest Tachycardia,
arrest Normal Normal Normal
Respiratory Normal Mechanical
ventilation
Gasping
breath, arrest Normal Normal Normal
Temp Normal Normal Hypothermic Normal Normal Fever
Metabolic acidosis Yes Yes Yes Yes Yes Yes
Abdomen Normal Soft, no
megally
Pain, soft,
coffee vomit Soft lax
Soft lax,
epigastric
pain,
vomiting
Soft lax
Kidney Acute renal
failure NA NA NA NA NA
CNS:
- CT scan
Diffused
edema,
anorexic
damage
Normal Normal Normal Normal Normal
- Confusion Yes Yes Yes Yes Yes Yes
- Repeated seizures NA Yes Yes NA NA NA
- Coma Yes Yes Yes No, drowsy No No, drowsy
NA: data not available.
J. Clin. Med. 2023,12, 4282 5 of 11
Table 4. Management courses of the six cases in the emergency department and hospital.
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6
IV normal saline (D5NS 100 mL/h) + + + + + +
Sodium bicarbonate infusion + + + + + +
Plasma protein fraction infusion + - - - - -
Hemodialysis - - - + + +
Mechanical ventilation + + + - - -
40 mEq KCl IV Intravenous infusion in
500 mL NSS over 4 or 6 h + + + + + +
Fomepizole 15 mg/kg IV as loading sode - - - + + +
Fomepizole 10 mg/kg IV 4 doses/2 days - - - + + +
Thiamine 100 mg IV/stat - - - + + +
Ethanol 600 mg/kg IV infusion - - +- - - -
Omeprazole 40 mg IV daily + + + + + +
Ranitidine 50 mg IV/stat - - + - - -
Diazepam 3 mg IV/stat - + + - - -
sc enoxaparin 4000 iu once a day + + - - + +
Vasopressor noradrenaline + + + - - -
Dopamine HCL 40 mcg/kg every 1 h + - - - - -
Potassium phosphate 21 mmol/day IV - + + - - -
Magnesium sulphate 2 g/day IV - + + - - -
KCl 600 mg tab tid PO - - - - + +
IV: Intra venous, KCl: Potassium chloride.
Table 5. Anion and osmolal gaps for the six cases.
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6
AG (mmol/L) 33.7 38.4 33.2 25.4 23 23.7
Mean ±SD 33.7 ±2.87 (died) 23.7 ±1.23 (survived)
p-value 0.037 (sig)
OG (mmol/kg) −18.8 −29.4 19.1 −15.0 −23.31 −13
Mean ±SD 19.10 ±6.04 (died) 15 ±5.47 (survived)
p-value 0.024 (sig)
AG: anion gap, OG: osmolal gap. Data are expressed as mean
±
SD. p-value was calculated to compare between
died and surviving cases regarding AG, and OG using independent ttest, where signifcance was set at p< 0.05.
Table 6. Outcomes for the six cases.
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6
Outcome Dead Dead Dead Improved Improved Improved
Causes of death
Post-cardiac arrest Post-cardiac arrest Post-cardiac arrest No No No
Anorexic brain
damage Pulmonary arrest Pulmonary arrest
2.2. Final Diagnosis
Methanol poisoning was confirmed in the six cases based on the signs of metabolic
acidosis, vision loss, optic nerve damage, and the drink brought by their relatives. The
methanol level was measured only for patient 2, while patients 1 and 3 died before sending
the samples to the toxicology center in Makkah (methanol was measured by GC/MS
Shimadzu, Poison Control Center Makkah, Saudi Arabia). The methanol levels of patients
4, 5, and 6 were not measured and treatment started with the empirical treatment of
methanol intoxication.
Treatment
Not all of the patients were treated with the appropriate antidotes, such as fomepizole,
due to the shortage of its availability in addition to the lack of efficient blood methanol
J. Clin. Med. 2023,12, 4282 6 of 11
measurement in the hospital’s laboratory. Treatment with ethanol was applied to patient
3, due to the unavailability of fomepizole, and because of the difficulty of administering
it without monitoring its concentration, the treatment with ethanol of patients 1 and 2
could not be applied or even continued for patient 3. Most of the patients were treated
with supportive care, inotropic support, vitamins (thiamin), and hemodialysis if possible.
Hemodialysis was performed on patients 4, 5, and 6 while failing in patients 1, 2, and 3 due
to their circulatory collapse.
2.3. Follow-Up and Outcome
Three patients died from post-cardiac pulmonary arrest after ICU admission. In
addition, patients number one and three rapidly died from multi-organ failure 10 h after
ICU admission. Patient number one showed diffused brain edema and anorexic brain
damage in the CT scan in addition to acute renal failure and other symptoms of methanol
poisoning, while patient number two died two days after ICU admission. The other three
patients survived and were discharged five days (patient 4), and 3 days (patients 5 and 6)
after ICU admission but with permanent optic nerve damage.
3. Discussion
Outbreaks of methanol poisoning have been described in the medical literature in
different regions around the world, in particular in Arab countries [
3
,
7
,
16
–
19
]. Even though
in Saudi Arabia a few outbreaks of methanol poisoning have occurred [
20
], they remain
undocumented. Herein, this article describes six cases of methanol poisoning in Saudi
Arabia with the goal of increasing awareness about the dangers of methanol poisoning
among healthcare staff.
In this study, we described the clinical symptoms, management procedures, and
outcomes of six methanol-intoxicated patients managed in Taif, providing an insight into
the limitations that have affected the treatment strategy and reviewing fundamental public
health issues in KSA that remain unresolved to date.
All six patients developed severe metabolic acidosis, the most common finding of
methanol poisoning, due to formic acid and formaldehyde accumulation [
6
,
7
]. In addition,
each patient had visual disturbances, the only specific characteristic of methanol poisoning.
Metabolic acidosis coupled with visual disturbances from methanol poisoning had been
reported in several studies, with a prevalence of approximately 30–60% on hospital admis-
sion [
21
–
23
]. In this study, all cases reported visual loss and toxic optic nerve damage. This
is in agreement with a previous case series study in KSA at the King Khaled Eye Specialist
Hospital and King Saud University Hospitals in Riyadh, that reported that 100% of cases
showed visual loss due to bilateral optic nerve damage, which is a late complication of
methanol poisoning, while other symptoms reported in the current study were not as-
sessed [
3
]. Formic acid accumulation in the eye causes blurred vision and finally vision loss
due to the lack of retinal mechanisms of formic acid detoxification [
5
,
7
]. Brain damage was
also present in our cases, where only patient 1 reported diffused brain edema and anorexic
brain damage, as seen in the CT scan. This patient with brain damage had shown more
severe methanol poisoning and more severe metabolic acidosis than the other patients,
without brain damage. A previous study supported this finding, where brain damage and
lesions were present in severe methanol poisoning cases with in patients with the highest
metabolic acidosis [24].
All cases were suspected to have methanol poisoning based on their symptoms and
history of alcohol and colonia ingestion. After ingestion, methanol may persist in the
body for as long as a week. It is water-miscible and distributes in total body water,
therefore, higher levels are attained in the aqueous and vitreous humors of the eye, CSF,
and gastric secretions than in blood [
16
,
25
]. Its volume of distribution ranges between
0.60 and
0.77 L/kg
[
16
,
26
]. The first indicators of methanol intoxication are difficult to
distinguish from normal ethyl alcohol effects within an hour, with mild symptoms such as
nausea, vomiting, and abdominal discomfort being similar to ethanol poisoning. Following
J. Clin. Med. 2023,12, 4282 7 of 11
a latent period of approximately 12–24 h, depending on the methanol dose consumed,
metabolic acidosis develops, and visual function deteriorates, ranging from blurred vision
and impaired visual fields to full blindness, side by side with symptoms such as headache,
dizziness, and vertigo. Worst of all, it takes 12–24 h to distinguish between methanol and
ethanol poisoning, and people are frequently heavily intoxicated and unconscious [
16
,
26
].
Once methanol poisoning is suspected, based on their symptoms and alcohol ingestion
history, their serum methanol must be measured, and this was not available for all six cases.
Hence, the osmolality gap and anion gap metabolic acidosis should be evaluated as soon as
possible to confirm methanol poisoning. The anion gap (AG) and osmolal gap (OG) have
been reported as necessary tools in the evaluation of methanol poisoning and for guiding
treatment procedures [
14
,
19
]. It has been reported that a high AG and OG are correlated
with severe and non-specific metabolic acidosis, with secondary respiratory dyspnea as a
result [
26
]. The AGs and OGs for the six cases were not calculated in the hospital. However,
in the present study the authors used the available data to calculate the AG and OG for the
purpose of evaluating the poisoning by methanol and the treatment procedures, which did
not follow a specific protocol (Table 5). The current study reports that those patients who
died had higher AGs and OGs, compared to those who survived (p-value = 0.037 for AG
and 0.024 for OG).
Metabolic acidosis is the main symptom of methanol poisoning and leads to other
symptoms and complications of methanol poisoning. However, rapid correction of metabolic
acidosis and elimination of formate is necessary and a cornerstone of methanol poisoning
management procedures [12,27].
Different antidotes have been reported to be used in the management of methanol
poisoning, trying to lower levels of formate, released from methanol metabolism, including
ethanol and fomepizole [
28
]. Fomepizole, is an ADH inhibitor, with a longer duration
of action; it prevents the conversion of methanol to its toxic metabolite formic acid [
28
].
It is given intravenously at a loading dose of 15 mg/kg within 30 min, then 10 mg/kg
every 12 h until the methanol level drops below 30 mg/dL. To overcome p450 enzyme
clearance, the dose of fomepizole should be raised after 48 h. Because hemodialysis also
removes fomepizole, the dosage should be adjusted during the hemodialysis procedure [
28
].
Fomepizole is recommended to be given when patients show severe metabolic acidosis
with high AG, OG, visual defects, and serum methanol > 20 mg/dL [
5
,
29
,
30
]. In this study,
it is noted that only three patients received fomepizole, while the other three did not meet
the aforementioned criteria for the use of fomepizole.
Ethanol, another antidote for methanol poisoning, acts by competing with methanol
for ADH; it is used in case of the unavailability of fomepizole and it has been reported to be
sufficient in preventing formate formation [
1
,
31
]. Every 1–2 h during methanol poisoning
treatment, serum levels of ethanol must be monitored. The level of ethanol in the blood
should be controlled within the range of 100–150 mg/dL to accomplish the therapeutic
aims [
32
]. A loading dose of 600 mg/kg (13 mmol/kg) is initially given to attain this goal.
The maintenance dose (66–154 mg/kg or 1.4–3.3 mmol/kg) is then administered orally or
intravenously to keep the blood ethanol level within the prescribed range [28,33].
Fomepizole is easier to dose, does not cause drunkenness, and inhibits alcohol de-
hydrogenase substantially, but it is also more expensive. Ethanol is less expensive, but it
is more challenging to dose precisely, necessitates close monitoring of the serum ethanol
content, and induces drunkenness that may require acute care monitoring [
34
,
35
]. Fur-
thermore, ethanol therapy may result in major problems such as hypoglycemia, changes
in awareness level, liver toxicity, or pancreatitis [
28
,
36
]. In our cases, it is noted that the
patients who survived, patients 4, 5, and 6, were administered with fomepizole in contrast
to those who died, while ethanol was given only to patient 3. The fomepizole-treated
patients also showed fewer complications and the best outcome when compared with
the non-fomepizole-treated patients. In agreement, a case report study had reported that
the use of fomepizole prevented vision defects and stabilized vital signs of a 1 year old
who ingested alcohol paste with 80% methanol [
37
]. In contrast, Holzman, Larsen (2021),
J. Clin. Med. 2023,12, 4282 8 of 11
reported that all cases of methanol poisoning died despite administering fomepizole and
hemodialysis [29].
Hemodialysis, including extracorporeal therapy, is another successful treatment for
methanol intoxication to correct acidosis and remove methanol from the blood [
38
]. Af-
ter being transferred to the ICU department, three of the patients (4, 5, and 6) received
hemodialysis while the others did not, due to circulatory collapse. Coma, seizures, early
signs of visual impairment, blood pH < 7.15, severe metabolic acidosis, AG > 24 mmol/L,
and high serum methanol concentrations are all reasons for hemodialysis [
12
]. Hemodialy-
sis was not administered to the patients who died (patients 1, 2, and 3) although they met all
these criteria, with pH < 7.15, AG > 24 mmol/L, coma, and visual impairment. In contrast,
hemodialysis was administered to the patients who survived (cases 4, 5, and 6) although
they did not meet all the criteria of hemodialysis. Patients 4, 5, and 6 had vision defects
but were conscious. Patient 4 had pH > 7.15, while patients 5 and 6 still had pH < 7.15.
Patients 5 and 6 had AG < 24 mmol/L, while patient 4 had AG > 24 mmol/L. However,
the patients who survived received hemodialysis sessions while those who died did not
and this, side-by-side with the use of fomepizole, enhanced the outcome of those who
survived over those who died and showed multi-organ failure. It has been noted that blood
pressure increased after the hemodialysis sessions, which is in agreement with a previous
case report study [
38
]. Another retrospective study has reported the beneficial effect of
hemodialysis and its rapid effect on the removal of methanol and its toxic metabolites. In
this study, 91 patients received hemodialysis and only 3 of them died, in agreement with
our study, while all of the surviving patients had hemodialysis sessions and all of those
who died did not receive hemodialysis [39].
To treat and correct severe metabolic acidosis, all six patients were given sodium
bicarbonates to reverse acidosis, which may also have had a good impact on the conversion
of formic acid to formate and the removal of formate, in agreement with other previous
studies [
26
,
29
,
35
,
38
,
40
]. Inotropic support including noradrenaline, dopamine, and potas-
sium chloride, in addition to mechanical ventilation, were given to the patients who died,
trying to overcome circulatory collapse and pulmonary cardiac arrest, but unfortunately,
they failed and the patients died from pulmonary cardiac arrest in addition to anorexic
brain damage in patient 1 [
41
–
43
]. Thiamine was used in patients 3, 4, 5, and 6 but we
criticize its role as it has very little beneficial effect on methanol poisoning. Its action is
beneficial in ethylene glycol poisoning but not methanol, as it promotes the conversion of
the toxic metabolite of ethylene glycol, glycolic acid, to α-hydroxy-βketoadipate [2].
Regarding the outcome of methanol intoxicated patients, it has been noted that three
of the patients died while the other three survived. The dead patients have been shown
to have had more severe metabolic acidosis with higher AG, electrolytes disturbance, and
inappropriate treatments as compared to the surviving patients. The deaths of patients 1–3
were due to pulmonary cardiac arrest, in addition to anorexic brain damage and renal failure
in patient 1. All of the cases suffered from visual impairment, but with severe symptoms in
the patients who died. On admission, low pH (pH
≤
7.00), coma, and insufficient ventilation
(PCO
2≥
23 mmHg) were found to be the biggest predictors of a poor prognosis after
methanol poisoning; these symptoms were present strongly in the cases of the patients who
died [
44
,
45
], which is in agreement with a study performed by Gouda, Khattab (2020) [
7
].
Gouda, Khattab (2020) reported that patients administered ethanol outside of hospital had
improved clinical outcomes [
7
,
44
]. The previous finding is consistent with the current study
where patients who were administered fomepizole survived. Methanol-induced vision loss
appears to have a less predictable outcome. However, it has been reported that more than
80% of patients showed an improvement in optic nerve conductivity during the first years
of follow-up [
45
]. In addition, no link has been found between visual sequelae and the
type of antidote used, or the mode of hemodialysis used, while only out of hospital ethanol
administration appeared to be beneficial, based on follow-up as seen in a recent methanol
poisoning outbreak in the Czech Republic [46].
J. Clin. Med. 2023,12, 4282 9 of 11
Furthermore, it has been noticed that patients who survived spent more time in the
hospital as compared to those who died, which may provide an insight into the correlation
between a poor prognosis and inappropriate treatment protocols, where a good prognosis
was noticed in patients who followed treatment protocols, including suitable antidotes, in
addition to extracorporeal therapy [29,38].
The current study was concerned about the fatal consequences of personnel shortages,
testing, and treatment availability (appropriate antidotes and extracorporeal treatments) in
KSA, which may become a problem in the event of a large methanol poisoning outbreak
based on the findings of this study. A high case fatality rate may stem from a lack of
awareness about methanol poisoning treatment among health professionals, as well as late
diagnosis of suspicious cases.
4. Limitations and Conclusions
One of the major limitations of this study was the inability to confirm methanol poi-
soning in the blood samples because, despite its importance, it is not a routinely requested
test. In all cases, empirical treatment was started based on the patient’s medical history or a
high clinical suspicion of methanol poisoning. The lack of awareness about the importance
of requesting a concomitant ethanol level measurement as part of the management plan
needs to be addressed.
In conclusion, in KSA hospitals with few resources, mass methanol poisoning poses a
serious threat. The lack of diagnostic testing and antidotes in the cases presented herein
was overcome by an urgent supply of supportive care, antidotes for some cases, and
hemodialysis. This study highlights the dangers of items that are sold without any warnings
or ingredients information. The dramatic consequences of methanol poisoning outbreaks
are not impossible to predict with the available resources. Awareness programs must
be provided for health care staff regarding treatment guideline protocols and diagnostic
criteria of methanol poisoning to be able to overcome methanol poisoning outbreaks.
Author Contributions:
Conceptualization, N.A. and G.I.A.; methodology, G.I.A., F.S.A. and K.M.A.;
validation, S.M.A., A.H.F. and Y.Z.A.; investigation, A.R.A.; resources, S.S.A.-G.; data curation, A.R.A.;
writing—original draft preparation; G.I.A. writing—review and editing, N.A., A.R.A., S.M.A., A.H.F.
and Y.Z.A.; visualization, S.S.A.-G.; supervision, A.R.A.; project administration, N.A. All authors
have read and agreed to the published version of the manuscript.
Funding: This study was funded by Umm Al-Qura University (Project number 43509006).
Institutional Review Board Statement:
The study was conducted in accordance with the Declaration
of Helsinki, and approved by the Institutional Review Board of Directorate of Health Affairs, Taif,
Research and Studies Department. IRB registration number with KACST, KSA: HAP-02-T-067,
approval number: 517, date: 12 February 2021.
Informed Consent Statement:
Written informed consent was obtained from the patients to publish
these case reports in accordance with the journal’s patient consent policy. For patients who were
unable to give written consent or deceased, it was obtained from the patients’ next of kin.
Data Availability Statement:
The data that support the findings of this study are available in
the manuscript.
Acknowledgments:
The authors would like to thank the Deanship of Scientific Research at Umm
Al-Qura University for supporting this work (Project number 43509006).
Conflicts of Interest: The authors declare no conflict of interest.
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