ORIGINAL ARTICLE

Year : 2022  |  Volume : 39  |  Issue : 1  |  Page : 48-52

Evaluation of brain death due to methanol intoxication

Tugce Mengi¹, Hüseyin Özkök², Özlem Öner³, Erdem Yaka¹, Bilgin Cömert², Ali Necati Gökmen^3
1 Departments of Neurology, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey
² Department of Internal Medicine, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey
³ Department of Anesthesiology and Reanimation, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey

Correspondence Address:
Tugce Mengi
Adult Intensive Care Unit, Niğde Training and Research Hospital, Niğde, Turkey.
Turkey

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/nsn.nsn_128_21

Objective: Intoxication may mimic brain death and cause brain death. In the literature, brain death due to methanol intoxication is limited to case reports. In this report, patients with methanol intoxication who had findings of imminent brain death were evaluated. Materials and Methods: The study population consisted of patients with methanol intoxication treated in the adult intensive care unit (ICU) between October 2014 and October 2020. The records in the hospital automation system of patients with methanol intoxication were evaluated retrospectively. According to the outcomes, the patients were divided into two groups: survivors and patients who had imminent brain death. Results: Eighteen patients with methanol intoxication were investigated. The brainstem reflexes disappeared in seven patients who were in a coma. The imminent brain death rate of patients with methanol intoxication was 39%. Patients who had imminent brain death had lower Glasgow Coma Scale scores during ICU admission and a higher ratio of pathologic neuroimaging findings due to methanol intoxication (P < 0.05). According to the clinical criteria and ancillary tests, four patients were declared brain dead. The brain death rate of patients with methanol intoxication was 22%. One of four patients with brain death was an organ donor. The liver was transplanted from our donor. Conclusion: Treatment should be initiated immediately in cases of methanol intoxication. Patients who do not respond well to treatment should be followed closely in terms of brain death. Based on published data and our personal experience, organ donations can be performed after appropriate investigations in brain death cases due to methanol intoxication.

Keywords: Brain death, intensive care, intoxication, methanol, organ donation

How to cite this article: Mengi T, Özkök H, Öner &, Yaka E, Cömert B, Gökmen AN. Evaluation of brain death due to methanol intoxication. Neurol Sci Neurophysiol 2022;39:48-52

How to cite this URL: Mengi T, Özkök H, Öner &, Yaka E, Cömert B, Gökmen AN. Evaluation of brain death due to methanol intoxication. Neurol Sci Neurophysiol [serial online] 2022 [cited 2022 May 16];39:48-52. Available from: http://www.nsnjournal.org/text.asp?2022/39/1/48/342361

Introduction

Brain death is the irreversible loss of activities in all areas of the brain, including the brainstem and cerebellum. The essential findings of brain death are coma, lack of brainstem reflexes, and apnea.^[1] Despite a careful neurologic examination, the process of determining brain death can be prone to misinterpretation. Fulminant Guillain–Barré syndrome, high cervical spinal cord injury, locked-in syndrome, hypothermia, and intoxications may mimic brain death.^[2],[3] Furthermore, intoxication may cause brain death.^[4] In the literature, brain death due to methanol intoxication is limited to case reports.^{[5],[6],[7],[8],[9],[10],[11],[12],[13],[14]}

In this report, patients with methanol intoxication who had findings of imminent brain death were evaluated.

Materials and Methods

The institutional research ethics board approved this study. The study population consisted of patients with methanol intoxication treated in the adult intensive care unit (ICU) between October 2014 and October 2020.

The diagnosis of methanol intoxication was based on patient history, methanol source, neurological signs and symptoms, increased anion gap, low bicarbonate level, and metabolic acidosis. According to the gas chromatography method, the absence of a history of illicit alcohol ingestion and the detection of toxic blood methanol levels (>20 mg/dL) was diagnostic.

The records in the hospital automation system of patients with methanol intoxication were evaluated retrospectively. Age, sex, source of methanol, methanol level, serum pH and anion gap at the time of hospital admission, Glasgow Coma Scale (GCS) scores, and brain stem reflexes (pupillary light reflex, corneal reflex, oculocephalic and oculovestibular responses, and gag and cough reflex) at the time of ICU admission, cranial computed tomography (CT) pathologic findings due to methanol intoxication, GCS and brain stem reflexes during follow-up in the ICU, apnea test, ancillary test, and outcomes were recorded on data collection forms. According to the outcomes, the patients were divided into two groups: survivors and patients who had imminent brain death.

Statistical analyses were performed using the SPSS 24.0 statistics package software. Categorical variables are expressed as frequency and percentage values. All variables are expressed as median (minimum–maximum). Continuous variables were compared using Student's t-test or the Mann–Whitney U test, and categorical variables were compared using the Chi-square or Fisher's exact test. P < 0.05 was accepted as statistically significant.

Results

Eighteen patients with methanol intoxication were investigated. Blood methanol concentrations were analyzed in a patient with dermal spirit use and in a patient whose history of illicit alcohol consumption was learned late. Blood samples of two patients were analyzed in another health institution because methanol levels could not be measured in our hospital. In 18 patients, the diagnosis of methanol intoxication was based on patient history, methanol source, neurological signs and symptoms, increased anion gap, low bicarbonate levels, and metabolic acidosis. The neurological signs and symptoms were blurred vision in six patients, reduced visual acuity in three, epileptic seizures in five, confusion in two, and coma in nine patients. The clinical characteristics of the patients with methanol intoxication on ICU admission are presented in [Table 1].

Table 1: The clinical characteristics of the patients with methanol intoxication at the time of intensive care unit admission Click here to view

All patients received the treatment protocol of methanol intoxication including ethanol or fomepizole bicarbonate and hemodialysis. Fomepizole or ethanol was used to decrease the conversion of methanol into formic acid. Hemodialysis and sodium bicarbonate were used to remove both parent and toxic metabolites from the blood and to correct metabolic acidosis. During the follow-up in ICU, GCS and brain stem reflexes, apnea test, ancillary tests, and death/discharge status are presented in [Table 2].

Table 2: Outcomes of patients with methanol intoxication Click here to view

The brainstem reflexes disappeared in seven patients who were in a coma. The imminent brain death rate of patients with methanol intoxication was 38.9% (7/18). Apnea tests were conducted and documented by an intensivist. Five patients did not tolerate the apnea test, becoming hypoxic or hemodynamically unstable, and the apnea test was aborted. Apnea tests were considered positive in two patients.

Ancillary tests were determined after evaluating the prerequisites and neurologic examinations. CT angiography was included in our brain death diagnosis protocol. CT angiography was performed in four patients. However, CT cerebral angiography could not be performed in the other three patients who were hemodynamically unstable. These three patients died before ancillary tests could be performed. CT cerebral angiographies showed absent cerebrovascular circulation in four patients. According to the clinical criteria and ancillary tests, four patients were declared brain dead. The brain death rate of patients with methanol intoxication in the ICU was 22.2% (4/18). The possibility of organ donation was offered to the families. One of four patients with brain death (25%) was an organ donor. The liver was transplanted from the donor. The relatives of the other three patients did not give permission for organ donation.

Probable predictors of outcome were compared between survivors and patients who had imminent brain death [Table 3]. The patients who had imminent brain death had significantly lower GCS scores during ICU admission and a significantly higher ratio of pathologic neuroimaging findings due to methanol intoxication (P = 0.002 and P = 0.004, respectively). Putaminal involvement (putaminal hypodensities and/or hyperdensities) was detected in 10 patients at the acute phase of methanol intoxication in cranial CT. The other pathologic findings were bilateral frontal lobe subcortical hypodensities, diffuse cerebral subcortical hypodensity, subarachnoid hemorrhage and/or pseudosubarachnoid hemorrhage, diffuse cerebral edema, and intraventricular hemorrhage in cranial CT.

Table 3: Probable predictors of prognosis in the acute phase of intoxication Click here to view

Discussion

In our study, the brain death rate of patients with methanol intoxication in the ICU was 22%. The first question to be asked is why methanol intoxication causes brain death. The central nervous system-depressing effects are due to organic solvent and toxic properties of formaldehyde and formic acid. In addition, the increased oxidative stress contributes to these effects as possible mechanisms.^[15]

The increasing demand for organs to be transplanted has made it possible to evaluate marginal donors necessary.^[16],[17] Thus, the standard criteria for the acceptance of organ donors have extended.^[18] Previously published reports showed that patients who died because of intoxication, including methanol, might form another significant pool of organ donors.^{[6],[9],[10],[11],[12],[13],[14],[16],[17],[18],[19],[20]} Despite this knowledge, they represent less than 1% of all organ donors.^[6]

There are doubts about organ donation in donors who die from intoxication. First, toxic substances, particularly liposoluble ones, are suspected to be present in the organs of the donor subject and cause intoxication in the recipients of these grafts.^[18] Second, there are concerns about the damage of the organs to be transplanted due to toxic substances.^[6] The reports of intoxication and organ donation have reduced these doubts. Successful organ transplant from donors with acute methanol intoxication has been reported.^{[6],[9],[10],[11],[12],[13],[16],[17],[18],[19],[20]} No complications or damage due to methanol and its products on transplanted organs have been noted.^[6] In our study, only one of the four patients (25%) became a utilized donor. The liver was transplanted from our donor. Successful liver transplantations have also been reported from patients with methanol intoxication.^{[9],[10],[12],[16],[18],[19],[20]}

Patients with methanol intoxication in the ICU should be followed closely for brain death. In our study, the imminent brain death rate of patients with methanol intoxication was 39%. “Imminent brain death” is defined as a state of deep coma (GCS 3/15), with irreversible catastrophic brain injury of known etiology, and the absence of three or more brainstem reflexes in patients requiring mechanical ventilation who are admitted to the ICU. The concept of imminent brain death enables recognizing patients who are likely to deteriorate to brain death.^[21] In our study, one of the two patients diagnosed as having imminent brain death progressed to brain death.

Various predictors may be used to describe imminent brain death in methanol intoxication. In our study, the patients who had imminent brain death had lower GCS scores during ICU admission and a higher ratio of pathologic neuroimaging findings due to methanol intoxication (P < 0.05). Previous reports about the predictors of prognosis in methanol intoxication have shown that poor prognosis was associated with coma at the time of hospital admission, serum pH below 7, and anion gap.^[22],[23] A limited number of studies evaluated the relationship between neuroimaging findings and prognosis.^[24],[25] In a study of 42 patients with methanol intoxication, pathologic findings in cranial CT were shown in 28 patients.^[25] It was detected that putaminal hemorrhage and insular subcortical necrosis were more common in patients who died.^[25] In a study conducted by Sefidbakht et al.,^[24] two of the nine patients with the most severe radiologic abnormalities due to methanol intoxication died. In our study, all patients with methanol intoxication who died in the ICU were diagnosed as having imminent brain death and/or brain death before they died. In other words, if patients with methanol intoxication do not respond well to treatment, they may progress to irreversible catastrophic brain injury and be candidates for brain death.

Brain death may be diagnosed by evaluating the prerequisites, neurologic examinations, and if necessary, ancillary tests.^[1],[2],[3] We evaluated these three items for the diagnosis of brain death in methanol intoxication. In cases of intoxication, a quantitative level of drug or toxin should be obtained before determining brain death.^[3] Unfortunately, many hospitals in Turkey are unable to analyze methanol. Therefore, the diagnosis of methanol intoxication is based on patient history, clinical findings, and neuroradiologic findings.^[26],[27] In the study by Kurtas et al., the blood methyl alcohol concentration was not analyzed at first or during hospitalization in 57% of cases of methanol intoxication.^[28] However, blood levels of methanol do not reflect concentrations in the brain, which may be lower.^[6]

The clinical examination of brain death is based on three main findings: coma, absence of brainstem reflexes, and apnea.^[3] Intoxication may cause brain death and also mimic brain death.^[2],[3],[4] When intoxication mimics brain death, brain stem reflexes generally remain intact, so a complete examination is essential.^[3] If the patient is in doubt under the influence of consciousness-changing drugs or toxins, physicians are wise to either prolong the period of delay in performing clinical brain death examinations or proceed with ancillary testing.^[1],[3] In previous reports, electrophysiologic tests, especially electroencephalography, were preferred as ancillary tests in patients with methanol intoxication who had findings of brain death.^{[10],[12],[16],[17]} In more recent reports, transcranial Doppler ultrasonography and technetium-99m cerebral perfusion testing were used as the ancillary tests.^[5],[14] We used CT angiography because CT angiography was included in our brain death diagnosis protocol.

In our study, the brain death rate of patients with methanol intoxication in the ICU was 22%. This rate provides valuable data because there are no reported data about the incidence of brain death, to the best of our knowledge. Treatment should be initiated immediately in cases of methanol intoxication. Patients who do not respond well to treatment should be followed closely in terms of brain death. Based on published data and our personal experience, organ donation can be performed after appropriate investigations in patients with brain death due to methanol intoxication.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 

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Tables

  [Table 1], [Table 2], [Table 3]