Mohammad Hossein Nikoo, Alireza Estedal, Maryam Pakfetrat, Firoozeh Abtahi, Seyed Taghi Heydari

1 Non-communicable Diseases Research Center, Shiraz University of Medical Sciences, Shiraz 71345-1877, Iran

2 Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz 71345-1877, Iran

3 Department of Internal Medicine, Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz 71345-1877, Iran

4 Departement of Cardiology, Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz 71345-1877, Iran

Iran experienced one of the largest methanol poisoning outbreaks shortly after the coronavirus pandemic due to misinformation about the beneficial effects of alcohol in preventing and treating this viral infection.According to the Iran Legal Medicine Organization (LMO), over 3,100 methanol toxicity cases and 728 deaths were reported across the country, resulting in a syndemic of methanol poisoning.There is very little literature on the electrographic predictors of cardiovascular mortality in methanol poisoned patients.Furthermore, there are only a few published studies on the electrocardiogram (ECG)manifestations in methanol poisoned patients.

However, it has yet to be determined whether the ECG findings can predict mortality. Our previous studyand Paasma et aldescribed the most common ECG findings in patients with methanol toxicity and investigated their relationship with the severity of intoxication, particularly in patients with blood levels of methanol exceeding the median lethal dose (LD). Following that, the purpose of this study was to re-examine possible prognostic factors associated with mortality risk and investigate the ECG findings associated with mortality in methanol toxicity.

METHODS

From March to April 2020, 356 patients with methanol toxicity were admitted to tertiary hospitals affiliated with Shiraz University of Medical Sciences for this retrospective cross-sectional study. We included all patients who drank a known alcoholic beverage with proven methanol impurity and developed clinical findings attributed to it. Previous myocardial infarction, supraventricular or ventricular arrhythmias, coronary artery bypass grafting (CABG), any known genetic cardiac disease such as Brugada, long QT syndrome, or short QT syndrome were all exclusion criteria.Albert et aldescribed the definitions of ECG parameters.Data on arterial blood gas measurements were collected (pH,bicarbonate [meq/L], and partial pressure of carbon dioxide[PCO]). A pH < 7.2 was def ined as severe acidosis.Based on Winter’s formula (PaCO=1.5×[HCO]+8±2), mixed metabolic and respiratory acidosis was identified in our patients as a lack of hyperventilation.As a result, in this study, a group with PaCO>1.5×[HCO]+10 was chosen as a lack of hyperventilation group.In addition, we calculated an angle known as the T slope in the following manner. First,we drew the T-wave symmetry line in all pericardial leads,which divided the T-wave into left and right sides. Then, for the right side of the T-wave, a tangent line was drawn. These two lines intersected at an angle. The complementary angle of this angle was named as T slope.

The Chi-square test was used to examine the relationships between mortality, acidosis, and ECG variables.Univariate logistic regression was used to calculate the odds ratio () and corresponding confidence interval (95%). The independent relationship between death, acidosis,and ECG variables was determined using multiple logistic regression, adjusted for sex and age. The-value <0.05 was considered to be statistically signif icant.

RESULTS

A total of 328 (92.1%) participants were male, and 162(45.5%) were under 30 years. In the univariate analysis,patients with corrected QT (QTc) ≥500 ms, QT dispersion(QTd) ≥40 ms, atrioventricular conduction block, Brugada pattern, J-point elevation, ST-segment elevation myocardial infarction (STEMI), bundle branch block, Osborn wave, severe metabolic acidosis, and a lack of hyperventilation with severe acidosis had higher mortality rates (Table 1). There was no correlation between severe acidosis and T slope, poor R-wave discovered that pH was the most important predictor of poor outcome and mortality in methanol poisoning. According to our f indings, higher levels of acidosis, higher partial pressures of carbon dioxide, and lower oxygen saturation were associated with increased mortality in these patients. These findings corroborate a multicenter study by Paasma et aland support the notion that these patients have difficulty in compensating for metabolic acidosis by inducing hyperventilation.

The most commonly reported ECG changes in methanol poisoning patients are sinus tachycardia, longer QTc, and T-wave changes. Other ECG findings include the Brugada pattern, QRS complex widening, and the induction of atrial fibrillation (AF).Furthermore, our recent publication on this topic revealed that J-point elevation, the presence of a U-wave, a fragmented QRS, and STEMI were the most common ECG changes in methanol poisoning patients.However, none of these studies found an ECG f inding to be a reliable predictor of mortality. This study revealed some progression, notch QRS, or low QRS voltage (>0.05).

After adjusting for age and sex, multiple logistic regression revealed an independent relationship between mortality rate and T slope, Brugada pattern, low QRS voltage, severe metabolic acidosis (pH<7.2), and a lack of hyperventilation with severe acidosis (Table 1).

DISCUSSION

Figures of coronavirus disease 2019 (COVID-19) cases,deaths, and mortality rates vary significantly from country to country.The pandemic has necessitated extraordinary actions by governments and the global medical community to maintain medical supplies and prevent rapid transmission. These responses have had an untoward impact on economies and fundamentally changed the practice of medicine and delivery of health care. The mortality rate in this study was 16.6%, which was comparable to other published data.Iranpour et alpreviously unknown ECG findings in methanol toxicity and suggested a link between the findings in this sample of deceased patients and mortality in cardiac electrical conduction disorders known as Brugada phenocopy. A study in Spain recently reported on the latter.This similarity can be based on ionic channel blockage by formaldehyde or other metabolites, and it can be convenient because of its potential to predict mortality.

Table 1. Association between death, ECG variables and acidosis evaluation in methanol toxicity with univariate and multiple logistic regression, n (%)

There was a case report on STEMI in methanol toxicity in the literature.However, due to the scarcity of cases, they could not determine the infarction rate and mortality hazard ratio in methanol poisoning. This ratio was calculated in our previous articleand was explained further in this one.

T slope showed a strong correlation with death when equal to or greater than 70°.Although a review of the literature reveals a few reports on repolarization abnormalities measured by T slope, such as the work of Strebel et alin myocardial infarction and Heijman et alin drug-induced ventricular arrhythmias, the signif icance of it remains to be determined in future studies.

Low QRS voltage was another remarkable ECG finding for death. This finding was reported for tamponade and severe heart failure patients, indicating a potentially dangerous situation.Damaged myocytes may be unable to produce enough electrical voltage gradient to be exposed as prominent electrical waves.

CONCLUSIONS

The study indicates that ECG can be a useful paraclinical tool in managing patients with methanol toxicity,potentially predicting critical outcomes such as mortality.Apart from the previously mentioned parameters such as acidosis, QTc prolongation, and a prominent U-wave, the Brugada pattern, low QRS voltage, and a steeply terminal T slope greater than 70° are all warning signs and predictors of mortality in methanol poisoning patients.

ACKNOWLEDGEMENTS

The authors would also like to show our great appreciation for help by Mohammadali Nikoo in scientif ic writing.

The study was supported by a grant from Research Deputy of Shiraz University of Medical Sciences (98-01-01-22074).

This study was approved by the ethics committee of Shiraz University of Medical Sciences (IR.SUMS.REC.1399.059).

They have no competing interests.

MHN and STH designed the study, analyzed the data, interpreted the results, and drafted the manuscript. ARE, MP,and FA contributed to data analysis and result interpretation. All authors have read and approved the manuscript.