Methanol intoxication including the counterfeit alcoholic beverages is allied to substantial morbidity and mortality that needs eminent health policies to effectively control the increasing rates (1, 2). In Egypt, methanol toxicity is quite common (3). Although methanol itself is not very toxic, it is metabolized by alcohol dehydrogenase into formaldehyde and then into formic acid.
These metabolites cause anion gap metabolic acidosis, blindness, irreversible brain damage, and finally death (4). Methanol intoxication cases cannot be easily identified specially when history is not available and entails a high level of suspicion. Rapid recognition and early treatment with alcohol dehydrogenase inhibitors are decisive, as the irreversible effects caused by formic acid is time-sensitive.
Benzodiazepines are tranquilizing and anxiolytic drugs, known to be safer than barbiturates by causing less respiratory depression in overdose settings. Though cases of serious and fatal benzodiazepine overdoses such as alprazolam intoxication have been reported with significant respiratory depression, it usually occurs in co-ingestion with another central nervous system depressant such as alcohol (5).
Liraglutide is a novel long acting glucagon-like peptide-1 (GLP-1) receptor agonist that mimics incretin and helps to maintain glucose homeostasis through the stimulation of glucose-mediated insulin secretion and inhibition of glucagon release in a glucose-dependent manner. Additional therapeutic effects include increased satiety and weight loss (6). The GLP-1 agonists are not expected to cause hypoglycemia as monotherapy in therapeutic doses for diabetic patients and they are not well studied in overdose and therefore information regarding acute overdose is limited to case reports (7). Prolonged hypoglycemia can lead to unconsciousness, repeated episodes of severe hypoglycemia can cause long term cognitive dysfunction (8).
In the current study, we aimed at presenting a case of combined exposure to these 3 substances in a male patient that ended in persistent coma, metabolic acidosis, and death.
This research explored a case of 43-year-old male who was not diabetic, nor an alcohol consumer, but treated with benzodiazepines for sleep disorders and anxiety. The patient unintentionally took 10 tablets of diazepam 10 mg over a period of 24 hours, aiming to sleep. He also consumed one glass of denatured ethanol containing methanol that he bought from the pharmacy (used for disinfection) that he mixed with a can of soda as a traditional advise from a friend to treat renal stones. The patient was on liraglutide subcutaneous injections for weight loss, with one injection 2 days before the hospital admission.
The family repudiated any history of trauma or major psychiatric disorder as he was a well to do, educated man with a permanent stable job. His medical history is free from any chronic diseases apart from history of renal stones that he tried to ingest alcohol the day before the admission to dissolve it after he had taken its ordinary medications.
The patient was presented to the emergency department with coma, apnea, and shock, his Glasgow Coma Scale score was 3/15, with bilateral constricted pupil, he was hypotensive his blood pressure was 60/40, his heart rate was 112, he was apneic, his oxygen saturation in room air was 80 by pulse oximetry, and his temperature was 37.
The examination showed generalized hypotonia, diminished reflexes, and absent plantar response with no meningeal signs. The patient was immediately intubated and mechanically ventilated on volume control mode. Resuscitation was done to the patient by IV fluid challenge of 1000 ml normal saline 0.9% infused over 30 minute, vasopressors and inotropes (noradrenaline started by 0.01 mic/kg/ min and titrated to reach systolic pressure 90), ABG showed severe mixed metabolic and respiratory acidosis where PH was 6.75, PCO2: 34.8, HCO3: 4.8, PO2: 82.4 (table 1), bicarbonate 150 meq of 8.4 % diluted in 1 liter of dextrose 5% was given IV infusion over one hour.
Random blood sugar showed hypoglycemia (50 mg/dl). 100 ml dextrose 25% was given IV. Urinary toxicology screening was done revealing positive benzodiazepines only for which 5 ampoules of flumazenil 0.5 mg IV sequentially were together with vitamin B 100 mg IV slowly and folinic acid 50 mg IV every 6 hours (table 2) Once blood pressure was stabilized emergency hemodialysis for 2 hours was done.
After the dialysis session the patient’s blood pressure was maintained on 90/60 by noradrenaline 3.3 mic/kg/min and adrenaline 2 mic/kg/min, HR: 110 b/min, GCS: 3/15, RR: 20 on ventilator volume control FiO2: 60%, temp: 37. The GCS did not improve above 3/15 and the pupils were dilated.
Laboratory follow up: repeated ABG showed metabolic acidosis, PH: 7-7.1, Hco3: 8-9 (table 1) and bicarbonate according to deficit was continued. Renal functions showed renal impairment with serum creatinine 2.6-2.8 mg/dl, BUN: 45mg/dl , liver functions were within normal , random blood sugar measurements were in a range of 70-75 mg/dl, Na and K range were (139-147 mmol/L) and (3.2-3.7 mmol/L), respectively, complete blood count with differential count was within normal. ECG showed inferior leads ischemia in a form of inverted T wave in II, III, aVf, and sinus tachycardia (figure 1). CT brain and CXR were done to the patient with no abnormality found.
severe acidosis persisted (table 1 ) along the 37 hours hospital stay, and inaudible blood pressure despite maximum vasopressors and inotropes, patient arrested for 18 minutes followed by return of spontaneous circulation (ROSC) for 5 minutes, with supraventricular tachycardia and 2 DC shock done then returned sinus. Patient arrested again with no ROSC for 40 minutes baseline ECG declared death after 2 hours on ventilator.
awareness about the combined effects of alcohol, benzodiazepines and hypoglycemic agents, had resulted in death of a fairly healthy young male patient.
Acknowledgment: the authors would like to acknowledge the patient’s family for their honesty, cooperation, and patience in detailed history narration.
Funding and support: None.
Conflict of Interest: None to be declared.