A total number of 356 patients were included in this study and most of the subjects were men, which can be explained by the cultural background and related social stigma of alcohol usage for women in Iran.
Compared to previous outbreaks [15, 16], the age distribution of the population was wider and included teenagers as well as the senior patients, sometimes in their 70’s. The involvement of the youths may be a matter of concern for social activists in Iran.
Different mortality rates have been reported for methanol intoxication, mostly because of definitions. Taiwan nationwide survey showed 40% long term mortality [17], while a study from UK reported a rate of 11% [8]. There is another Iranian research with the rate of 40% by Sanaie-Zade [9]. The mortality rate in our series was slightly less than 17%, which seems to be more than comparable articles6 by Zardasht Jaff [8], however, this mortality is in-hospital mortality in a referral center and those who managed on outpatient basis were not included. This mortality and ocular and brain damage rate are in agreement with some previous outbreaks reports [16, 18–20].
Although in previous report from the UK [8] the most common finding was sinus tachycardia, most cases in this study occurred to have normal heart rate; however, the tachycardia proved to be an index of severity in our research and the lesser prevalence may be due to less severe intoxication in our patients. The heart rate above 100 was present in 25.3% of the sample, which was nearly six times as great as bradycardia (rate below 60). That is to say, roughly three quarter of our cases’ rate was in normal range.
Although there are few case reports for myocardial infarction in methanol toxicity [19], our survey is the first which could determine the prevalence of this complication (Fig. 1), however, the exact pathophysiologic mechanism yet remains to be explained. We propose following hypotheses: 1) this infarction noted in relatively young patients without usual risk factors for atherosclerosis [20]. 2) severe acidosis cause bleeding tendency due to reduction of fibrinogen level. Sometimes in situ thrombosis may occur, with ongoing disseminated intravascular coagulation and possible myocardial infarction [21]. 3) possible pathophysiologic mechanism may be endothelial dysfunction, a known entity in reduced extracellular PH, such a dysfunction will end in vasodilation however, frustratingly [22]. 4) acidosis causes vasodilatation and therefore spasm cannot be responsible for the occurrence [23]. This warrants further investigation and research.
J point elevation was the most prevalent finding in our survey; therefore, repolarization abnormalities were tried to be categorized as early repolarization, Brugada, QT prolongation syndrome. The only consistently correlated variable with the severity of disease was QTc prolongation more than 500. The QT prolongation was reported in nearly all of the previous studies, as well [3, 24, 25]. However, its significance could not be emphasized due to the lower volume in older reports. Prolongation of repolarization, measured in many ways, is a hallmark of electrical instability and predictor of cardiac arrest and sudden cardiac death. QTc prolongation is the most commonly used indicator, however, prolongation less than 500 msec. may be interpreted doubtfully. Accordingly, we approached to values above 500 as an independent marker of severity [26, 27].
We noted two type 1 Brugada ECG pattern in two brain-dead patients as terminal event before their arrest which bears similarity with the pattern in some head injured patients before their death in Neurosurgery Intensive care unit, during Propofol infusion [28, 29].
The best independent ECG indicators of methanol toxicity severity were QTc > 500 and heart rate more than 100. Interestingly, severe poisoning was strongly associated with myocardial infarction and atrioventricular block in our survey. (Table 2)
Table 2. Association between PH and ECG variables in methanol toxicity with univariate and multiple logistic regression.
| PH | P-value | Odds ratio (95% CI) Univariate | P-value | Odds ratio (95% CI) Multiple | P-value |
> 7 | <=7 |
QTC | < 500 | 233 (85.3) | 40 (14.7) | < 0.001 | 1 | - | 1 | - |
>=500 | 41 (60.3) | 27 (39.7) | 3.836 (2.126–6.922) | < 0.001 | 3.247 (1.605–6.569) | 0.001 |
QT dispersion | < 40 | 148 (84.6) | 27 (15.4) | 0.044 | 1 | - | 1 | - |
>=40 | 126 (75.9) | 40 (24.1) | 1.740 (1.011–2.995) | 0.046 | 1.177 (0.620–2.237) | 0.618 |
T slope | < 69 | 184 (81.1) | 43 (18.9) | 0.700 | 1 | - | 1 | - |
>=70 | 96 (79.3) | 25 (20.70 | 1.114 (0.642–1.934) | 0.700 | 1.291 (0.656–2.543) | 0.460 |
AVB | No | 270 (82.3) | 58 (17.7) | < 0.001 | 1 | - | 1 | - |
Yes | 10 (47.6) | 11 (52.4) | 5.121 (2.077–12.622) | < 0.001 | 5.981 (1.476–24.227) | 0.012 |
Rate | 60–100 | 208 (84.2) | 39 (15.8) | 0.026 | 1 | - | 1 | - |
< 59 | 8 (66.7) | 4 (33.3) | 2.667 (0.766–9.289) | 0.123 | 1.634 (0.328–8.148) | 0.549 |
> 100 | 63 (72.4) | 24 (27.6) | 2.032 (1.136–3.634) | 0.017 | 2.262 (1.152–4.442) | 0.018 |
Brugada | No | 264 (81.5) | 60 (18.5) | 0.034 | 1 | - | 1 | - |
Yes | 16 (64.0) | 9 (36.0) | 2.475 (1.044–5.869) | 0.04 | 3.190 (0.979–10.386) | 0.054 |
J elevation | No | 85 (85.0) | 15 (15.0) | 0.164 | 1 | - | 1 | - |
Yes | 189 (78.4) | 52 (21.6) | 1.599 (0.831–2.924) | 0.166 | 1.128 (0.526–2.418) | 0.757 |
STEMI* | No | 268 (83.0) | 57 (18.2) | < 0.001 | 1 | - | 1 | - |
Yes | 24 (66.7) | 12 (33.3) | 9.745 (3.507–27.081) | < 0.001 | 12.386 (3.681–41.682) | < 0.001 |
BBB* | No | 256 (81.8) | 57 (18.2) | 0.031 | 1 | - | 1 | - |
Yes | 24 (66.7) | 12 (33.3) | 2.246 (1.061–4.754) | 0.035 | 2.316 (0.857–6.259) | 0.098 |
poor progression | No | 256 (81.3) | 59 (18.7) | 0.083 | 1 | - | 1 | - |
Yes | 16 (66.7) | 8 (33.3) | 2.139 (0.887–5.308) | 0.090 | 2.549 (0.936–6.937) | 0.067 |
low voltage | No | 262 (80.6) | 63 (19.4) | 0.398 | 1 | - | 1 | - |
Yes | 10 (71.4) | 4 (28.4) | 1.663 (0.505–5.477) | 0.403 | 1.905 (0.489–7.418) | 0.353 |
*BBB=bundle branch block, STEMI=ST segment elevation myocardial infarction, AVB=atrioventricular conduction block, P value less than 0.05 considered significant