Methanol poisoning in Tunisia: Report of 16 cases

Abstract

Methanol poisoning continues to be a public health problem in Tunisia in spite of the different legislative measures. We report a series 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 to 36). 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 48 hours), and a median serum methanol concentration of 1.4 g/L (range 0.19 to 3.62 g/L). Clinical signs included central nervous system 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 in eleven patients (69%) because of visual disturbances and/or metabolic acidosis. One patient developed irreversible bilateral blindness and another unilateral blindness secondary to optic neuropathy. Statistical significant risk factors for the developing of visual disturbances were found to be the ingested quantity of methanol, the latent period, acidosis and serum methanol concentration on admission.

Keywords:

• Methanol poisoning
• Spirits
• Cologne
• Blindness
• Optic neuropathy
• Hemodialysis

Introduction

Methanol poisoning is an important public health problem because of its severe consequences (metabolic disturbances, permanent neurological dysfunction, and serious visual impairment). Also known as wood alcohol, methanol is a component of washing fluids, antifreeze formulations, photocopying fluids, perfumes, and paint removers. Toxicity can occur from dermal application, inhalation, or ingestion (1,2). Legislation supported by the Tunisian Ministries of Health and the Environment was enacted in 2000 to control alcohol production. Despite this legislation, methanol exists illegally in products such as spirits and cologne. The aim of this case series report is to emphasize the severity of acute methanol poisoning in Tunisia.

Methods

All patients admitted for acute methanol poisoning after two festival periods (December 2003 and April 2004) were included. 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 Physiology Score (SAPS II) and the Acute Physiology and Chronic Health Evaluation (APACHE II). The serum methanol level was measured by gas chromatography. An analysis of methanol elimination kinetics was performed in each patient.

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

Results

The study population consisted of 16 patients (15 men and one woman). 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), and a median APACHE II of 8 (range 6 to 36). No patient had a prior history of neurological or visual disturbances. The main source of acute poisoning was a mixed preparation of cologne and coca (65% methanol concentration) in 15 patients and spirits in one case (patient 8). The methanol was consumed in festival context because of its low cost. The median ingested quantity was 250 ml (range 30 to 1000) what was equivalent to 162 g of methanol (range 19.5 to 650).

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 (range 6 to 48). At admission, central nervous system (CNS) effects were 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), and hemodynamic failure and shock in 3 patients who required mechanical ventilation and hemodynamic support (Table 1). Funduscopic visualization was normal in 13 patients, including those with visual impairment. Pseudopapillitis was present in two severely poisoned patients. Evoked cortical potentials (ECP) performed in seven patients suffering from visual impairment were abnormal in two patients. ECP and visual field testing showed bilateral optic neuropathy in one patient suffering from blurred vision and unilateral optic neuropathy in the patient suffering from dyschromatopsia and scotoma. There was no information about the electroretinogram (ERG).

Table 1. Clinical features and laboratory chemistry at admission

Case	Sex/Age	SAPS II	APACHE II	Latent period (h)	Medical delay (h)	Symptoms	Ingested quantity (mL)	MeOH serumLevel (g/L)	pH	HCO3^−	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	Survivor
13	M/23	10	3	–	36	Vertigo, bradycrdia	30	3.56	7.14	7	Survivor
14	M/19	20	10	–	48	None	150	1.3	7.18	10.2	Survivor
15	M/21	12	7	18	36	Nausea, vomiting	80	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.

The median serum methanol level upon admission was 1.4 g/L (range 0.19 to 3.62). Arterial blood gases showed metabolic acidosis in 15 patients with a median pH of 7.22 (range 6.80 to 7.42) and median HCO₃⁻ of 10 mmol/L (range 4 to 18). Laboratory tests showed renal failure in 4 cases (mean serum urea of 9.7 ± 3.1 mmol/L [27.2 ± 8.7 mg/dL] and creatinine of 155 ± 38 μmol/L [1.75 ± 0.43 mg/dL]), rhabdomyolysis in three patients (mean creatine phosphokinase 1113 ± 716 UI/L), and hyperglycemia in seven patients (mean blood glucose 15.6 ± 9.8 mmol/L [280.8 ± 176.4 mg/dL]).

Intravenous sodium bicarbonate was administered to 15 patients in whom the serum pH level was under 7.35. Thirteen patients (81%) received intravenous ethanol therapy (bolus of 0.6 g/kg followed by continuous administration at 130 mg/kg/h) until methanol blood levels were undetectable or until the patients were asymptomatic with a normal serum pH. Folic acid was given as a 50 mg intravenous dose every 4 hours for 24 hours in 15 patients (94 %). Hemodialysis (for 3 to 6 hours at a blood flow rate of 300 ml/ min) was performed in 11 patients because of visual disturbances or metabolic acidosis. The first dialysis run resulted in a mean reduction in serum methanol concentraion of 79.4% (range 66.3 and 100%), a normalization of the arterial blood pH mean 7.38 ± 0.03 (range 7.35 to 7.41), and a resolution of visual impairment in seven patient. Three patients received two hemodialysis runs because of persisting visual disturbances (see Table 1). Three patients (19%) died within six hours of admission from refractory shock.

Statistically significant risk factors for the developing of visual disturbances were found to be the quantity of ingested methanol, the latent period, the acidosis, and the serum methanol level at admission (see Table 2).

Table 2. Risk factors of visual disturbances

Risk factors	Presence of visual disturbances (n = 11)	Absence of visual disturbances (n = 5)	P
Latent period (h)	9.2 ± 5.5	16.6 ± 8.08	0.04
Recovery time (h)	32 ± 13.5	36 ± 6.9	NS
Ingested quantity of methanol (g)	462 ± 350	105 ± 60	0.0001
GCS	11.2 ± 5.7	14.8 ± 0.4	NS
SBP	12.1 ± 4.1	12.5 ± 1.2	NS
pH	7.10 ± 0.2	7.30 ± 0.07	0.04
HCO3−(mmol/L)	8.7± 5.8	14 ± 3.7	NS
Methanol serum level (g/L)	2.2 ± 1.1	0.84 ± 0.62	0.01
Urea (mmol/L)	6.6 ± 3.7	5.45 ± 1.8	NS

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

Discussion

Methanol poisoning can cause severe toxicity that is attributed to the metabolite formic acid, which inhibits the cytochrome oxidase system necessary for ATP production, causing tissue hypoxia and lactate formation (1,3,4). Sources of methanol differ from one country to another (1–3,5). In our series, the main source of methanol was ingested a cologne 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 metabolites accounts for the latent period between methanol ingestion and clinical manifestations. Serious symptoms observed in our series were coma in 19% of cases, and visual effects (impairment, blurred vision, and dyschromatopsia) in 69% of cases who didn't suffer from any visual disturbances previously. The occurrence of unilateral blindness in one patient is unusual. Ocular toxicity depends on the severity of exposure and may be related to selective accumulation of formate in the retina and vitreous humor compared with other regions of the CNS. Blindness appears to be associated with formate production, acidosis, and local ischemia (1–3,5). Ophthalmic electrophysiological tests such as ERG and ECP have been reported to be more sensitive indicators of retinotoxicity (2,5,7) so their use, even if the funduscopic examination is normal, should be considered. In our series both ECP and visual fields detected abnormalities in three patients despite normal funduscopy.

Intravenous ethanol infusion was given to 13 patients (81%) instead of fomepizole, which is not available in Tunsia. The first line recommended antidote is fomepizole (7); it has an affinity for alcohol dehydrogenase (ADH) 500-1,000 times higher than of ethanol and has been shown to reduce and reverse visual impairment despite its potential to inhibit retinol dehydrogense (an ADH isoenzyme that is essential to vision) after methanol poisoning (4,8–12). Recent recommendations limit hemodialysis indications to elevated serum methanol concentration in addition to prolonged fomepizole administration (4,13). In our series, the ingested quantity of methanol, severe metabolic acidosis, and the serum methanol concentration on admission were found to be statistically associated with the presence of visual disturbances. Mathieu et al found that serum methanol concentration was not correlated with visual damages or mortality (14–16). However, formic acid concentrations in blood and urine correlated well with the severity of effects. This makes formic acid a better indicator of methanol toxicity, when measured 48 h after methanol ingestion and after therapeutic intervention (17,18).

Conclusion

Acute methanol poisoning is a potentially fatal public health problem in developing countries. For this reason, public education about the consequences of methanol consumption and legislative control should be emphasized. In addition, government authorities should be encouraged to include fomepizole in the list of necessary antidotes.

Acknowlegment

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