Methyl alcohol poisoning: an autopsy study of 28 cases.

BV Mittal, AP Desai, KR Khade 
 Department of Pathology, Seth G.S. Medical College, Parel, Bombay, Maharashtra.

Correspondence Address:
B V Mittal
Department of Pathology, Seth G.S. Medical College, Parel, Bombay, Maharashtra.

Full Text

::   Introduction

Methyl alcohol (MA) is a cheap and potent adulterant of illicit liquor. Many outbreaks of methyl alcohol poisoning have occurred in different parts of India, taking a heavy toll of mortality and morbidity. In spite of this, there is a paucity of documented autopsy data. This has prompted us to report the autopsy data from 28 fatal cases of methyl alcohol poisoning at the King Edward Memorial Hospital, Mumbai in a single outbreak in August, 1988.

::   Material and method

Ninety-seven cases with suspected methyl alcohol poisoning were admitted to K. E. M. Hospital in August 1988. They were aggressively treated with 7.5% sodium bicarbonate with a loading of 180 meq/L followed by 18 meq/L. Absolute alcohol (in 2% dextrose) at 9 gms/hour was also administered. There were 28 fatal cases, who were brought for post-mortcm. Stomach contents, slices of liver, spleen, kidneys along with blood were sent to the Government Forensic Laboratory for the detection of methyl alcohol. Gross findings from all the organs were noted. 6? thick paraffin sections from all the organs were studied for histopathology. Routine H. E. stain was done on all sections and PAS on all renal tissues. Clinical details were recorded from the medical records.

::   Results

Of the 28 fatal cases of methyl alcohol poisoning, 21 were males and 7 females. Maximum number of cases (67.85%) was in the 4th and 5th decade. There were 5 cases (17.8%) in the 3rd decade and 2 cases each in the 6th and 7th decade. The interval between the consumption of the adulterated drink and presenting to the hospital with symptoms was variable, minimum being 7 ½ hours whereas the maximum interval was 5 days in one case. Majority of the cases reported to the hospital within 12-24 hours.



Clinical symptoms [Table:1]

Central nervous systcm (CNS) involvcment in the form of unconsciousness, scmi-consciousness, giddiness and visual symptoms were the predominant presenting features. Shock either on admission or as a late event was noted in 89% of the cases. Minimum fatal period was 7 ½ hours, but in majority of the cases, death occurred within 48 hours from the time of consumption of the adulterated alcohol. Four cases survived for 5 to 12 days (death occurred after five days in two cases, 6 days and 12 days in one case each). In 2 cases, the exact time of consumption of alcohol was not available but these patients died within 15 minutes and 3 hours after admission respectively.

Autopsy data

CNS involvcment [Table:2] and renal changes were the most consistent findings and were seen to a variable extent in all cases. Shrinkage and degeneration of parietal cortical neurons were the commonest findings (85.70%) whereas tcmporal cortex (28.5%), cerebellar granular layer (32.1%) and Purkinje cells (28.5%) were affected less often. Putamental degeneration and necrosis were seen in 1 case each. Changes in the optic nerve and retina could not be studied as eye balls were not available for study but significant changes of sponginess (2 cases) and Haemorrhage (one case) were observed in the optic chiasma.

Renal changes [Table:3] such as varying degrees of renal tubular degeneration (severe cloudy or vacuolar change) with patchy necrosis were seen in all the cases. Severe congestion of peritubular capillaries (71.42%), moderate glomerular capillary dilatation and congestion (78.57%), mild endothelial swelling (35.7%) and mild mesangial proliferation (35.7%) was the other significant renal findings.

Variable affection of other organs was observed; the chief findings were as follows: mild pulmonary oedema (64.28%), cloudy changes in the myocardium (42.5%), congestion and patchy Haemorrhage in stomach mucosa (21.3%), acute pancreatitis (3.5%), fatty change in the liver (67.88%) and micro vesicular fat in hepatocytes (42.55%).

Methyl alcohol (MA) levels in blood, stomach and viscera [Table:2]

Methanol levels in blood as well as in the viscera were variable. Average methyl alcohol level was 155.87 mg % and maximum 420.4 mg %. No methyl alcohol was detected in the blood of 7 cases; however, in all these cases, viscera and stomach contents revealed presence of methyl alcohol.

Stomach contents obtained from stomach washes on admission as well as post-mortcm samples were sent for chcmical analysis. The minimum methyl alcohol level in the stomach washes was 11.0 mg % and maximum was 112.3 tug (mean 67.5 mg %). Values in the post-mortcm samples were also variable. Trace amounts of methyl alcohol were detected in 4 cases. One case was negative for methyl alcohol. Maximum level was 42.8 mg/100 gm, of tissue with the mean value of 22.4 mg/100 gm. In 7 cases, it was less than 10 mg/100 gm. In 4 cases who died 5 to 12 days after consumption of the drink methyl alcohol levels varying from 5 mg % to 20.8 mg % were noted in the post-mortcm stomach contents. These levels were however lower than the methyl alcohol levels in the stomach washes on admission. (Methyl alcohol level between 18.6 mg % and 54.7 mg %).

Methyl alcohol was detected in the viscera of all but one case. Trace values were noted in 7 cases and in 5 cases methyl alcohol levels were less than 10 mg %. Maximum level of methyl alcohol in the viscera was 43.5%.

::   Discussion

Adulteration of cheap liquor by methyl alcohol is common in India. In 1971, 90 deaths were reported from Khopoli due to methanol poisoning. Subsequently, 100 deaths from Hyderabad, 20 from Madras and more than 300 deaths from Bangalore have been reported[1]. There was a similar outbreak in 1983, when 47 cases were admitted to King Edward Memorial Hospital, Bombay. Two cases died before starting the treatments[8]. The present episode took comparatively a high toll of mortality with 28 fatal cases (28.86%) of the 97 cases admitted.

Intoxication with methyl alcohol can occur with ingestion, inhalation of methanol vapour or by absorption through the skin. Methanol is oxidised to formaldehyde and then quickly further oxidised to formic acid, both in vivo and in vitro[4]. It is these metabolic products, which have a toxic action. The time interval between the ingestion of the adulterated drink and the presentation with symptomatology is due to the time taken for the metabolism of methanol. In our series, the minimum time interval was 7 1/2 hours, whereas the maximum latent period was 120 hours. Bonnets et al[3] reported a latent period of 40-72 hours while Ravichandran et a1[8] 4-60 hours. Death occurred in less than 48 hours after symptoms appeared in 75% of the cases. In 25% cases, death was a late event, occurring 5-10 days after the consumption of the drink.

During methanol poisoning in man, the concentration of methanol and formic acid in the blood are quite variable. Lunds in 5 fatal cases of methyl alcohol poisoning, found blood methyl alcohol and formic acid values varying from 9-68mg/dl. Although, in most of the reported cases, blood methanol levels were greater than 100 mg/dl, deaths have occurred with methyl alcohol level as low as 5.7 mg/dl. In our study of 28 fatal cases too, the methyl alcohol levels were variable with an average methyl alcohol value of 155.87 mg %. In 7 cases no methyl alcohol was detected, 3 of these cases had died 5 days or more after the consumption of the adulterated drink, and methyl alcohol could have been metabolised to formaldehyde or formic acid or resecreted in the stomach (methyl alcohol was detected in the post-mortcm stomach contents in all these three cases). However, in one additional fatal case where death was a late event (after 12 days), 72.5 mg % of methyl alcohol was detected in the blood. This is difficult to explain. The fact that methyl alcohol was detected in the post-mortcm stomach contents 5 days after admission in 4 cases, raises the question as to whether these cases who survive longer should be given repeat stomach washes to clear the resecreted methanol in the stomach to reduce the prolonged toxic effects.

Symptomatology noted in most of our cases was very similar to the reported series[3],[4],[6],[8]. However, the incidence of shock and unconsciousness was higher, since this series refers only to the fatal cases. Besides the direct toxic effects of metabolic products of methyl alcohol, main effects are because of the metabolic acidosis, as is reflected by the decreased scrum bicarbonate levels and pH of the blood. Neuronal degeneration and shrinkage as well as cerebral oedema were noted in most of the cases, however, no direct relationship between the degree of these changes and levels of methanol could be obtained. Serum bicarbonate levels were available in only seven cases and these too showed no direct correlation with the CNS changes. These changes in the neurons rescmble anoxic changes and could be related to the terminal event of respiratory arrest in most of these cases. Orthner [7] described putamental necrosis in 41 out of the 124 patients with methyl alcohol poisoning. In our series, putamental degeneration and necrosis was noted in one case each.

Ocular lesion consists of destruction of ganglion cells of retina probably due to locally formed formaldehyde. In none of our cases, however, eyeballs were available for study.

Microvesicular fat in the hepatocytes was seen in 42.7% of the cases. Such steatosis is known for ethionine, arotic acid, tetracycline and puromycine toxicity, and is due to either ATP depletion or prevention of protein synthesis by binding to RNA or blocking ribiosomes. Interference in synthesis of apoprotein moiety leads to defective synthesis of I required to rcmove rapids from liver [9]. Though the exact mechanism in the cases of methyl alcohol poisoning is unknown, one can deduce that microvesicular steatosis could be toxic in origin.

Approximately 3-10% of administered dose of methanol is excreted unchanged by the kidneys[2]. Highest concentration of formaldehyde has been found in the kidney, liver and gastro-intestinal tract by studies using C[14] labelled methanol. Considering that both methanol and its toxic metabolises are concentrated in the kidneys it is not difficult to explain the severe degenerative changes in the renal tubules and peritubular capillaries. Glomerular changes too rescmble the early changes seen in cases of viper bites, Haemolytic uracmic syndrome and toxacmia of pregnancy, all of which have a known toxic aetiology.

Thus changes in the various organs were probably of toxic aetiology, either mediated through the direct toxic action of the metabolite formaldehyde or the metabolic acidosis due to formic acid production.

References