Single center experience of managing methanol poisoning in the hilly state of Uttarakhand: A cross sectional study.

BACKGROUND: In this article, we describe our experience in managing one of the worst tragedies of an outbreak of methanol poisoning in the state of Uttarakhand in February 2019. It was reported that more than 100 people of Uttarakhand and neighboring districts of Uttar Pradesh succumbed to death after consuming this toxic alcohol laced with methanol.
MATERIALS AND METHODS: Demographic, clinical, and biochemical data were collected retrospectively from the hospital record section of the tertiary care hospital in the state of Uttarakhand.
RESULTS: Ninety-three patients of methanol poisoning were attended by the emergency medicine department of our hospital. The mean age of the patients was 38.9 ± 10.3 years. Majority of the patients were males (92/93). The most common clinical symptoms were gastrointestinal (56; 60.2%) followed by neurological (21; 22.6%) and respiratory (18; 19.3%). Most of the patients presented within 12-24 h after consumption of methanol. The mean of latent time of presentation was 4.8 ± 2.6 h. The mean values of pH, bicarbonate levels, lactate, and base deficit were 7.13 ± 0.6, 12.3 ± 6.4, 2.6 ± 0.8, and 15.6 ± 3.8 mmol/l, respectively. Acute kidney injury (26; 27.9%), blurring of vision (9; 9.6%), and sepsis (6, 6.4%) were common complications. Seven patients (7.5%) succumbed to death. Intensive alkali therapy was the main modality of treatment. Ethanol therapy was useful in patients resistant to alkali therapy. Sixteen (17.2%) patients with acute methanol poisoning were dialyzed once.
CONCLUSION: Patients with acute methanol poisoning have varied presentations. Gastrointestinal symptoms are the most common presentation. Such outbreaks account for the heavy toll of mortality and morbidity in the society. Prompt diagnosis and a protocol based treatment can have a significant impact on the outcome of these patients. Thus, public health warning should be immediately issued with initial presentation of the casualties. Copyright:

INTRODUCTION

Acute methanol poisoning is a global crisis. Many such outbreaks have been reported in the past not only from India but also from all over the world. These outbreaks mainly affect poor and vulnerable strata of the society. Many a time, if not reported, these outbreaks go unnoticed.[12345] Methanol, an organic solvent, has been used for industrial purposes and is prepared from wood by the destructive distillation process. The minimal reported lethal dose of methanol is 15 ml of 40% methanol. The highest recorded dose of methanol is 500–600 ml.[6] In suspected cases of methanol poisoning, it is prudent to obtain the blood methanol levels to estimate the severity of signs and symptoms of methanol poisoning. However, methanol levels cannot be obtained immediately, and the treatment should be initiated as soon as possible based on the point-of-care markers such as bicarbonate and lactate levels and base deficit.[4] The metabolism of methanol is caused by enzymatic degradation by dehydrogenase into formaldehyde and formic acid. These byproducts are highly reactive and bind to tissue proteins, leading to oxidative damage to the cells.[7]

It has been observed now that formic acid is mainly responsible for most of the symptoms of methanol poisoning. Usually, there is a time lag of 12–24 h between exposure of methyl alcohol and presentation of signs and symptoms of toxicity. However, this time lag is variable. A thorough examination and extensive workup is required in these patients on arrival to the emergency department.[8] In this study, we present our experience in managing the outbreak of hooch tragedy in the hilly state of Uttarakhand.

MATERIALS AND METHODS

This described outbreak of methanol poisoning took place at Uttarakhand and neighboring districts of Uttar Pradesh in the month of February 2019. More than 100 people succumbed to death before receiving medical care. All India Institute of Medical Sciences, Rishikesh, received around 93 patients of methanol poisoning over a period of 4 days. A detailed history was obtained from the patients, relatives, and prehospital personnel. Clearly, the clinical history was suggestive of accidental intake of toxic illicit liquor. Detailed clinical examination including vital signs, mental status, and ophthalmological screening was done for all the patients. After immediate primary assessment airway, breathing and circulation were taken care of in all the patients. Intubation was done in indicated patients. Hypotension was treated with intravenous crystalloid fluids. Ophthalmological screening was done to assess ocular injury signs such as sluggish reaction to light, hyperemia of discs, congested and edematous retina, blurred disc margins, and optic atrophy. All the patients received intravenous pyridoxine (50 mg), thiamine (100 mg), methylcobalamine, and oral folic acid. Arterial blood gas analysis was done in all the patients. In patients with pH <7.3, intravenous sodium bicarbonate 1 meq/kg was given as bolus dose followed by intravenous infusion (as per calculated dosage). Intravenous isotonic saline and diuretics were given to promote forced diuresis. Sixth hourly arterial blood gas analysis was done. The treatment was modified by the values of pH, bicarbonate levels, base deficit, and anion gap. Patients with pH <7.30 and bicarbonate <20 meq/dl received ethanol (4–8 ml per kg of 10% ethanol solution followed by 0.5–1 ml/kg of 10% ethanol). Patients who did not improve with intravenous bicarbonate therapy and ethanol underwent hemodialysis in the intensive care unit. The above treatment was continued until arterial pH, bicarbonate levels, and serum sodium levels were normalized. A standard treatment protocol was followed in all the patients.

The demographic, clinical, and biochemical data were collected retrospectively from the hospital record section. It was analyzed, and an attempt was made to know the prognostic factors of methanol poisoning. The authors of this manuscript declare that this scientific work complies with reporting quality, formatting, and reproducibility guidelines set forth by the EQUATOR Network.

RESULTS

A total of 93 patients of methanol poisoning, 92 (98.9%) males and one female patient, were admitted in a tertiary care hospital of Uttarakhand. The mean age of the patients was 38.9 ± 10.3 years. Of 93 patients, 64 (68.8%) patients were poor laborers, 20 (21.5%) sweepers, whereas 9 (9.6%) patients were unemployed. The mean latency period of presentation (time interval of first symptom of presentation) was around 4.8 ± 2.6 h; however, most of the patients were brought to the hospital between 12–24 h of methanol intake [Table 1].

Table 1

Demographic and clinical characteristics of acute methanol poisoning (n=93)

General charcteristics	Number (%)
Age (maximum-minimum)	38.9±10.3 (70-19)
Sex
Male	92 (98.9)
Latency of presentation in hours	4.8±2.6
Admitted in ICU (%)	21 (22.6)
Clinical profile (%)
Gastrointestinal symptoms	56 (60.2)
Chest pain	15 (16.1)
Visual symptoms	12 (12.9)
neurological symptoms	21 (22.6)
Breathlessness	18 (19.3)

ICU: Intensive care unit

Gastrointestinal symptoms in the form of nausea, vomiting, and abdominal pain were observed in 56 (60.2%) cases followed by neurological symptoms in 21 patients (22.6%). Visual symptoms in the form of blurred vision were seen in 12 (12.9%) patients. Of 12 patients, 7 (58.3%) patients had normal fundus, 2 (16.6%) patients had bilateral disc pallor, and two (16.6%) patients had bilateral hyperemia of disc whereas only one patient had evidence of papilledema on fundoscopy.

The mean values of arterial pH and bicarbonate levels were 7.13 ± 0.6 and 12.3 ± 6.4 mmol/l, respectively. The mean value of hematocrit was 47.8 ± 3.9 [Table 2]. More than 90% of the patients received the intensive alkali therapy. Ethanol was given in 24 (25.8%) patients. Sixteen patients (17.2%) were dialyzed once [Table 3].

Table 2

Laboratory profile of patients with acute methanol poisoning

Biochemical variable	Mean SD
Arterial pH	7.13±0.6 (lowest pH - 6.7)
HCO3(mEq/l)	12.3±6.4
Lactate	2.6±0.8
Base deficit (mmol/l)	15.6±3.8
Serum creatinine (mg/dl)	1.3±0.4
Serum potassium (mEq/l)	3.4±0.9
Hb (G/dl)	13.3±0.8
PCV (%)	47.8±3.9

PCV: Packed cell volume, Hb: Hemoglobin

Table 3

Treatment characteristics of patients with acute methanol poisoning (n=93)

Treatment	Number of patients (%)
Ethanol	24 (25.8)
Hemodialyzed once	16 (17.2)
Hemodialyzed twice	9 (9.6)
Intensive alkali therapy	90 (96.7)

Acute kidney injury (26; 27.9%), blurring of vision (9; 9.6%), and sepsis (6; 6.4%) were common complications in patients with acute methanol poisoning during hospital stay [Table 4]. Seven patients (7.5%) succumbed to death.

Table 4

Complications profile during hospital stay of acute methanol poisoning (n=93)

Complication	Number of patients (%)
Blurring of vision	9 (9.6)
Vision loss	3 (3.2)
Acute kidney injury	26 (27.9)
Sepsis	6 (6.4)
Intracranial bleed	3 (3.2)
Death	7 (7.5)

Comparison between the clinical and laboratory parameters of survivors and nonsurvivors of patients with methanol poisoning was mentioned in Table 5. Visual and neurological symptoms were more common in nonsurviving patients with methanol poisoning than in survivors. All the patients who succumbed to death were in altered sensorium at the time of admission to the intensive care unit and underwent hemodialysis.

Table 5

Clinical and biochemical parameters of survivors and nonsurvivors patients

S No	Clinical and biochemical parameters	Expired (n=7)	Survived (n=86)	P
1	Abdominal pain, n (%)	2 (28.5)	78 (90.7)	Not significant
2	Vomiting, n (%)	4 (57.1)	67 (77.9)	Not significant
3	Visual blurring, n (%)	5 (71.4)	4 (4.6)	<0.05
4	Altered sensorium, n (%)	7 (100)	14 (66.6)	<0.05
5	Coma, n (%)	4 (57.1)	0	<0.05
6	Sepsis, n (%)	3 (42.8)	3 (3.4)	<0.05
7	Hemodialysis, n (%)	7 (100)	9 (10.4)	<0.05
8	Mean pH	7.01±0.04	7.13±0.06	<0.05
9	Mean bicarbonate levels	6.2±5.7	12.3±6.4	<0.05
10	ICU admission, n (%)	7 (100)	14 (16.2)	<0.05

ICU: Intensive care unit

DISCUSSION

Methanol poisoning is one of the common poisoning outbreaks in India, affecting mainly lower and uneducated strata of society. It is a cheap substitute used as an adulterant in the locally sourced liquors. Provisionally, many such outbreaks of hooch tragedy have been reported not only from India but also from other parts of the world such as Kenya and Libya in 2013 and 2014, respectively.[12345] The outbreak highlighted multiple health challenges such as delay in onset of symptoms, variation in presentation and symptom profile, management difficulties including diagnosis and treatment, increased burden (economic and workforce) on health-care system, and high mortality and morbidity rates. Thus, collaborative efforts of both public health departments and emergency medical services of the hospital to raise awareness of such outbreaks and for timely treatment of these patients are pivotal to prevent mortality and morbidity.[5]

Demography, clinical, and biochemical parameters

The mean age of presentation of patients with methyl alcohol poisoning was 38.9 ± 10.3 years. This signified that such outbreaks are affecting the earning members of society. The age of presentation is comparable to a study done by Jarwani et al. from Gujarat. Usually, there will be a delay in between exposure of methanol to presentation. This delay occurs as a result of a conversion of methanol to formaldehyde and then to formic acid by enzyme alcohol dehydrogenase.[4] Gastrointestinal symptoms such as pain abdominal, nausea, and vomiting are the most common symptoms in patients with methyl alcohol poisoning. When consumed in large amounts, these patients present commonly with altered sensorium and coma in the later stages. Characteristic visual symptoms and signs clinch the diagnosis. Previous studies have also highlighted similar observations.[23]

In our study, visual symptoms were seen in 12 (12.9%) patients, of which 9 (9.6%) patients had complaints of blurred vision, while 3 (3.2%) patients suffered from visual loss. A study by Dethlefs and Naraqi described ocular manifestations of methanol poisoning. It described that seven patients of methanol poisoning had transient ocular abnormalities, such as papilledema, optic disc hyperemia, and decreased pupillary reactions to light, whereas eight patients had permanent ophthalmic lesions.[9] Thus, these patients should undergo a detailed ophthalmic examination. The underlying pathogenesis is optic nerve demyelination caused by the destruction of myelin by formic acid.[10] Even though 30 ml of 40% methanol is considered as a minimum lethal dose, as minimum as of 10 ml also can cause blindness. This variability is explained due to various factors such as methanol susceptibility variation among individuals, associated ethanol ingestion (that will dilute the effects of methanol), and unreliability of amount of methanol ingested.[1112]

The role of formic acid is confirmed by previous studies in the toxic syndrome of methanol poisoning. Formic acid results in metabolic acidosis in these patients. Thus, formic acid level is used as a sensitive and specific method to confirm methanol poisoning in these patients.[12] In our study, metabolic acidosis was present in more than 90% of cases of methanol poisoning. The mean values of arterial pH and sodium bicarbonate levels were 7.13 ± 0.6 and 12.3 ± 6.4 mmol/dl, respectively. In our study, we observed neurological symptoms in 21 (22.6%) patients, and intracranial bleed was seen in 3 (3.2%) patients. All the three patients succumbed to death and had severe metabolic acidosis at the time of admission. Hemorrhagic brain lesions are common complications of methanol poisoning. The most common site affected is the putamen. The known risk factors of developing brain lesions are severe degree of academia, higher base deficit, serum lactate levels, and formic acid concentrations.[13141516] Increased PCV and lower potassium levels were observed in our study. Similar findings were studied by a previous study by Zadeh et al. as prognostic factors of lethality in methanol poisoning.[17]

In our study, acute kidney injury observed in 26 patients (27.9%). The incidence of acute kidney injury is variable among different studies. Chang et al. study on 50 methanol patients showed acute kidney injury in 33 patients (66%) and concluded as a useful predictor of hospital mortality.[18] In a study by Verhelst et al., acute renal injury was found in 15 of 25 (60%) patients.[19] Salek et al. study showed acute renal injury in 15.4% of cases. However, nephrotoxic effect of methanol is still uncertain.[20] Various factors such as blood methanol levels, formate concentrations, age, and comorbidities such as hypertension, diabetes, cardiovascular status, and preexisting chronic kidney disease will account for acute kidney injury. However, further clinical studies required for conclusive evidence in this topic.[17]

Triggers

More than 60% of the patients in our study belong to lower socioeconomic strata of society and were laborers by occupation. In developing countries, methanol is used as a cheap and readily available substitute for ethanol and is used in illicit liquors.[5]

Causes of delayed diagnosis

The outbreaks previously confirmed a generalized delay in the intake of methanol, appearance of symptoms, and recognition of symptoms and initiation of treatment. This has been attributed to inadequate knowledge of profile of symptoms of methanol poisoning. If adequate and reliable history is unavailable, these patients are generally missed. Usually, these patients are recognized and treated adequately if a mass casualty is notified. This poses a major challenge to the health-care system of India.[21]

Solutions suggested

Spreading awareness about methanol poisoning among medical officers at periphery and emergency care physicians at tertiary care hospitals is required for better coordination and improved management of these patients. A protocol should be formulated for the early recognition and treatment of these patients. This should also include the use of point-of-care markers such as arterial blood gas analysis, detection of formate using dipstick methods, and electrolyte levels.[22] Mass media and community leaders should aim for active case finding to limit such outbreaks.

CONCLUSION

Patients with methanol poisoning present with gastrointestinal, neurological, and visual symptoms. Prompt diagnosis and treatment can prevent morbidity and mortality. Collaborative efforts of local leaders, media, and emergency physicians are required not only to timely manage these cases but also to limit the spread of such outbreaks.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethical conduct of research

This study was approved by the Institutional Review Board / Ethics Committee. The authors followed applicable EQUATOR Network (http://www.equator-network.org/) guidelines during the conduct of this research project.