Clinical Toxicology (2007) 45, 717–720 Copyright © Informa Healthcare USA, Inc.ISSN: 1556-3650 print / 1556-9519 onlineDOI: 10.1080/15563650701502600

LCLTCASE REPORT

Methanol poisoning in Tunisia: Report of 16 cases

Methanol poisoning in TunisiaNOZHA BRAHMI, M.D.1, YOUSSEF BLEL, M.D.1, NOUR ABIDI, M.D.1, NADIA KOURAICHI, M.D.1, HAFEDH THABET, M.D.1, ABDERRAZEK HEDHILI, PH.D.2, and MOULDI AMAMOU, M.D.1

1Department of Intensive Care Medicine and Clinical Toxicology, (CAMU), Tunis, Tunisia2Toxicological Laboratory, Centre d’Assistance Médicale Urgente (CAMU), Tunis, Tunisia

Methanol poisoning continues to be a public health problem in Tunisia in spite of the different legislative measures. We report aseries of 16 cases of methanol poisoning admitted to our Intensive Care Unit between December 2003 and April 2004. The patients’median age was 21.5 years (range 16 to 53 years) with a median SAPS II of 14 (range 12 to 84) and an APACHE II of 8 (range 6 to36). The median latent period was 9.5 hours (range 4 to 24 hours) with a delay to medical consultation of 36 hours (range 6 to 48hours), and a median serum methanol concentration of 1.4 g/L (range 0.19 to 3.62 g/L). Clinical signs included central nervoussystem symptoms (69%), gastrointestinal complaints (87%), visual disturbances (69%) and metabolic acidosis (94%). Three patients(19%) required mechanical ventilation because of deep coma or shock and died within 6 hours. Hemodialysis was performed ineleven patients (69%) because of visual disturbances and/or metabolic acidosis. One patient developed irreversible bilateralblindness and another unilateral blindness secondary to optic neuropathy. Statistical significant risk factors for the developing ofvisual disturbances were found to be the ingested quantity of methanol, the latent period, acidosis and serum methanol concentrationon admission.

Keywords Methanol poisoning; Spirits; Cologne; Blindness; Optic neuropathy; Hemodialysis

Introduction

Methanol poisoning is an important public health problembecause of its severe consequences (metabolic disturbances,permanent neurological dysfunction, and serious visualimpairment). Also known as wood alcohol, methanol is acomponent of washing fluids, antifreeze formulations, photo-copying fluids, perfumes, and paint removers. Toxicity canoccur from dermal application, inhalation, or ingestion (1,2).Legislation supported by the Tunisian Ministries of Healthand the Environment was enacted in 2000 to control alcoholproduction. Despite this legislation, methanol exists illegallyin products such as spirits and cologne. The aim of this caseseries report is to emphasize the severity of acute methanolpoisoning in Tunisia.

Methods

All patients admitted for acute methanol poisoning after twofestival periods (December 2003 and April 2004) wereincluded. Demographic data, sources and amount of methanol,

circumstances, latent period, clinical features, management,and outcomes were collected from the medical register.Severity was assessed by the Simplified Acute PhysiologyScore (SAPS II) and the Acute Physiology and ChronicHealth Evaluation (APACHE II). The serum methanol levelwas measured by gas chromatography. An analysis of metha-nol elimination kinetics was performed in each patient.

Data were statistically analyzed with SPSS 11.0. Resultswere expressed as means ± standard deviation (SD), medians(range) and proportions. The Student t test was used for com-parisons; a p of <0.05 was considered significant. This studywas approved by the Hospital’s institutional review board.

Results

The study population consisted of 16 patients (15 men and onewoman). The study population had a median age of 21.5 years(range 16 to 53), a median SAPS II of 14 (range 12 to 84), anda median APACHE II of 8 (range 6 to 36). No patient had aprior history of neurological or visual disturbances. The mainsource of acute poisoning was a mixed preparation of cologneand coca (65% methanol concentration) in 15 patients andspirits in one case (patient 8). The methanol was consumed infestival context because of its low cost. The median ingestedquantity was 250 ml (range 30 to 1000) what was equivalentto 162 g of methanol (range 19.5 to 650).

Received 17 March 2006; accepted 28 November 2006.Address correspondence to Nozha Brahmi, M.D., Department of

Intensive Care Medicine and Clinical Toxicology, 2 Rue Raspail -1008 Montfleury, Tunis, Tunisia. E-mail: nozha_brahmi@yahoo.fr

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After a median latent period of 9.5 hours (range 4 to 24),patients developed headache and gastrointestinal symptoms;the median delay to medical consultation was 36 hours (range6 to 48). At admission, central nervous system (CNS) effectswere present in 69% (11 cases) including vertigo, headache,and coma; visual symptoms were present in 62.5% (10 cases)with blurred vision (4 cases), visual impairment (4 cases),dyschromatopsia (1 case) and bilateral blindness (1 case);gastrointestinal effects were present in 87% (14 cases), andhemodynamic failure and shock in 3 patients who requiredmechanical ventilation and hemodynamic support (Table 1).Funduscopic visualization was normal in 13 patients,including those with visual impairment. Pseudopapillitis waspresent in two severely poisoned patients. Evoked cortical

potentials (ECP) performed in seven patients suffering fromvisual impairment were abnormal in two patients. ECP andvisual field testing showed bilateral optic neuropathy in onepatient suffering from blurred vision and unilateral optic neu-ropathy in the patient suffering from dyschromatopsia andscotoma. There was no information about the electroretino-gram (ERG).

The median serum methanol level upon admission was 1.4g/L (range 0.19 to 3.62). Arterial blood gases showed meta-bolic acidosis in 15 patients with a median pH of 7.22 (range6.80 to 7.42) and median of 10 mmol/L (range 4 to18). Laboratory tests showed renal failure in 4 cases (meanserum urea of 9.7 ± 3.1 mmol/L [27.2 ± 8.7 mg/dL] andcreatinine of 155 ± 38 μmol/L [1.75 ± 0.43 mg/dL]),

Table 1. Clinical features and laboratory chemistry at admission

Case Sex/Age SAPS II APACHE IILatent

period (h)Medical delay (h) Symptoms

Ingested quantity (mL)

MeOH serumLevel (g/L) pH Outcome

1 M/16 14 8 8 26 Vertigo, headache, GI, VI

200 0.9 7.32 18 Survivor

2 M/17 12 8 6 36 Drowsiness, vertigo, GI

300 3.62 7.17 7 Survivor

3 M/24 12 9 4 6 Vertigo, VI, GI

500 3.56 7.14 7 Survivor

4 M/23 12 6 11 45 Headache, GI, VI

200 0.76 7.25 7.5 Survivor

5 M/29 84 36 – 36 Coma, BV, GI, shock

– 1.4 6.80 3.3 Died

6 M/20 14 8 7 12 Drowsiness, BV, GI

300 3.6 7.16 4 Survivor

7 M/20 81 35 – 30 Coma, BV, shock

– 2.5 6.99 6.9 Died

8 F/53 14 7 – 40 Vertigo, headache, VI

1000 1.3 7.42 22 Survivor

9 M/27 78 30 – 48 Coma, shock, BV, GI

1000 1.9 6.61 4 Died

10 M/23 11 6 – 36 Vertigo, blindness, chest tightness

300 1.9 7.19 15 Survivor

11 M/21 14 8 18 36 Nausea, dyschromatopsia

100 1.15 7.28 10 Survivor

12 M/17 12 8 – 36 None 70 0.24 7.34 15 Survivor13 M/23 10 3 – 36 Vertigo,

bradycrdia30 3.56 7.14 7 Survivor

14 M/19 20 10 – 48 None 150 1.3 7.18 10.2 Survivor15 M/21 12 7 18 36 Nausea,

vomiting80 0.19 7.35 16.8 Survivor

16 M/22 16 9 24 36 Nausea 100 1.6 7.26 10 Survivor

GI: gastrointestinal signs; VI: visual impairment; BV: blurred vision.

HCO (mmol/L)

3-

HCO3-

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Methanol poisoning in Tunisia 719

rhabdomyolysis in three patients (mean creatine phosphokinase1113 ± 716 UI/L), and hyperglycemia in seven patients (meanblood glucose 15.6 ± 9.8 mmol/L [280.8 ± 176.4 mg/dL]).

Intravenous sodium bicarbonate was administered to 15patients in whom the serum pH level was under 7.35. Thir-teen patients (81%) received intravenous ethanol therapy(bolus of 0.6 g/kg followed by continuous administration at130 mg/kg/h) until methanol blood levels were undetectableor until the patients were asymptomatic with a normal serumpH. Folic acid was given as a 50 mg intravenous dose every 4hours for 24 hours in 15 patients (94 %). Hemodialysis (for 3to 6 hours at a blood flow rate of 300 ml/ min) was performedin 11 patients because of visual disturbances or metabolic aci-dosis. The first dialysis run resulted in a mean reduction inserum methanol concentraion of 79.4% (range 66.3 and100%), a normalization of the arterial blood pH mean 7.38 ±0.03 (range 7.35 to 7.41), and a resolution of visual impair-ment in seven patient. Three patients received two hemodial-ysis runs because of persisting visual disturbances (see Table1). Three patients (19%) died within six hours of admissionfrom refractory shock.

Statistically significant risk factors for the developing ofvisual disturbances were found to be the quantity of ingestedmethanol, the latent period, the acidosis, and the serum meth-anol level at admission (see Table 2).

Discussion

Methanol poisoning can cause severe toxicity that is attrib-uted to the metabolite formic acid, which inhibits the cyto-chrome oxidase system necessary for ATP production,causing tissue hypoxia and lactate formation (1,3,4). Sourcesof methanol differ from one country to another (1–3,5). Inour series, the main source of methanol was ingested acologne with a methanol concentration of 65%. In Turkey(1), sources of methanol were cologne (72.6%), spirits(10.6%) and antifreeze (2.7%).

The time needed to accumulate methanol metabolitesaccounts for the latent period between methanol ingestionand clinical manifestations. Serious symptoms observed inour series were coma in 19% of cases, and visual effects(impairment, blurred vision, and dyschromatopsia) in 69% ofcases who didn’t suffer from any visual disturbances previ-ously. The occurrence of unilateral blindness in one patient isunusual. Ocular toxicity depends on the severity of exposureand may be related to selective accumulation of formate inthe retina and vitreous humor compared with other regions ofthe CNS. Blindness appears to be associated with formateproduction, acidosis, and local ischemia (1–3,5). Ophthalmicelectrophysiological tests such as ERG and ECP have beenreported to be more sensitive indicators of retinotoxicity(2,5,7) so their use, even if the funduscopic examination isnormal, should be considered. In our series both ECP andvisual fields detected abnormalities in three patients despitenormal funduscopy.

Intravenous ethanol infusion was given to 13 patients(81%) instead of fomepizole, which is not available in Tun-sia. The first line recommended antidote is fomepizole (7); ithas an affinity for alcohol dehydrogenase (ADH) 500-1,000times higher than of ethanol and has been shown to reduceand reverse visual impairment despite its potential to inhibitretinol dehydrogense (an ADH isoenzyme that is essential tovision) after methanol poisoning (4,8–12). Recent recom-mendations limit hemodialysis indications to elevated serummethanol concentration in addition to prolonged fomepizoleadministration (4,13). In our series, the ingested quantity ofmethanol, severe metabolic acidosis, and the serum methanolconcentration on admission were found to be statisticallyassociated with the presence of visual disturbances. Mathieuet al found that serum methanol concentration was not corre-lated with visual damages or mortality (14–16). However,formic acid concentrations in blood and urine correlated wellwith the severity of effects. This makes formic acid a betterindicator of methanol toxicity, when measured 48 h aftermethanol ingestion and after therapeutic intervention (17,18).

Table 2. Risk factors of visual disturbances

Risk factorsPresence of visual

disturbances (n = 11)Absence of visual

disturbances (n = 5) P

Latent period (h) 9.2 ± 5.5 16.6 ± 8.08 0.04Recovery time (h) 32 ± 13.5 36 ± 6.9 NSIngested quantity of methanol (g) 462 ± 350 105 ± 60 0.0001GCS 11.2 ± 5.7 14.8 ± 0.4 NSSBP 12.1 ± 4.1 12.5 ± 1.2 NSpH 7.10 ± 0.2 7.30 ± 0.07 0.04HCO3− (mmol/L) 8.7± 5.8 14 ± 3.7 NSMethanol serum level (g/L) 2.2 ± 1.1 0.84 ± 0.62 0.01Urea (mmol/L) 6.6 ± 3.7 5.45 ± 1.8 NS

GCS: Glasgow Coma Scale; SBP: systolic blood pressure.

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Conclusion

Acute methanol poisoning is a potentially fatal public healthproblem in developing countries. For this reason, public edu-cation about the consequences of methanol consumption andlegislative control should be emphasized. In addition, govern-ment authorities should be encouraged to include fomepizolein the list of necessary antidotes.

Acknowlegment

For their collaboration and invaluable support in this investi-gation, we thank the staff at the Toxicological Laboratory andthe School of Pharmacy.

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