A 33-year-old unemployed man was brought to the emergency department after ingesting 60 tablets of an over-the-counter painkiller along with 10 Diclofenac pills (25 mg each) and consuming alcohol. He ingested these substances approximately 9 hours before admission. On arrival, the patient was unconscious and in shock, with a blood pressure of 54/34 mmHg, a heart rate of 122 beats per minute (bpm), and severe metabolic acidosis. He was noted to be in a deep coma, with small pupils and no response to painful stimuli. Arterial blood gases showed a pH of 7.0, pCO₂ of 4 kPa, and severely elevated lactate. His labs were significant for hyperkalemia (K+ 5.9 mmol/L), elevated creatinine (226 μmol/L), and urea (6.3 mmol/L), suggestive of renal impairment. The patient’s serum ethyl alcohol level on admission was 110 mg/dL, and serum. After intubation and administration of activated charcoal, his condition worsened, with the development of bradycardia (30 bpm) and hypotension, necessitating aggressive treatment, including bicarbonate infusion. Eventually, after 24 hours, his condition improved, and he was extubated and discharged after three days, with full recovery of renal function.
Physical Examination:
General appearance: Unconscious, unresponsive male in deep coma.
Vital signs:
Blood pressure: 54/34 mmHg
Heart rate: 122 bpm (initially), later dropped to 30 bpm
Respiratory rate: Assisted ventilation
Temperature: Normal
HEENT: Small, reactive pupils, no spontaneous movements.
Cardiovascular: Tachycardic initially, later developed bradycardia.
Respiratory: Intubated, on ventilator support.
Abdomen: Soft, non-tender, no organomegaly.
Neurological: Deep coma, no response to painful stimuli, absent spontaneous movements.
Course of Treatment:
Initial management: The patient was intubated and administered activated charcoal to reduce the absorption of ingested toxins.
Progression: The patient's condition worsened, developing bradycardia (30 bpm) and hypotension, necessitating aggressive treatment with bicarbonate infusion to manage acidosis and hypotension.
Outcome: After 24 hours of intensive treatment, the patient’s condition stabilized. He was extubated and discharged 3 days later, with full recovery of renal function.
Which of the following best explains the cause of the patient’s severe metabolic acidosis?
a) Alcohol-induced ketoacidosis
b) Diclofenac-induced renal failure
c) Overdose of acidic metabolites from aspirin
d) Inhibition of electron transport by NSAIDs
Reveal the answer
The correct answer to the case of severe metabolic acidosis is (d) Inhibition of electron transport by NSAIDs. This explanation is supported by research showing that non-steroidal anti-inflammatory drugs (NSAIDs), such as Diclofenac, can impair mitochondrial function by inhibiting oxidative phosphorylation. This leads to reduced ATP production and an accumulation of acidic intermediates, particularly lactic acid, which results in lactic acidosis.
Supporting Literature:
NSAIDs and Mitochondrial Dysfunction: Diclofenac and other NSAIDs have been shown to inhibit mitochondrial complex I, a critical component of the electron transport chain. This impairment reduces aerobic respiration, causing lactate build-up and subsequent lactic acidosis (Sandoval-Acuña et al., 2012).
Lactic Acidosis in Drug Toxicity: NSAID-induced mitochondrial dysfunction is a well-known mechanism leading to lactic acidosis. This inhibition results in the accumulation of lactic acid due to blocked lactate transport and impaired cellular respiration (Emoto et al., 2002).
Why the Other Options Are Incorrect:
(a) Alcohol-induced ketoacidosis: While the patient had alcohol in his system, there were no signs of ketonemia or ketonuria. Alcohol-induced ketoacidosis typically presents with ketosis, which was not observed in this case (Palenzuela et al., 2005).
(b) Diclofenac-induced renal failure: While renal impairment was present, it does not fully explain the severe metabolic acidosis. Diclofenac-induced renal toxicity primarily affects kidney function through prerenal mechanisms, not by directly causing acidosis (Choi et al., 2005).
(c) Overdose of acidic metabolites from aspirin: There is no indication that the patient ingested aspirin, and the absence of hyperventilation, a common feature in aspirin toxicity, also rules out this option (Shah et al., 2011).
Conclusion:
The patient’s presentation of severe metabolic acidosis, hypotension, and coma was primarily attributed to the ingestion of a large quantity of Diclofenac, compounded by alcohol consumption. The patient’s severe lactic acidosis was likely caused by inhibition of mitochondrial oxidative phosphorylation due to Diclofenac overdose, which impaired ATP production and led to the accumulation of acidic intermediates, particularly lactate. The patient responded well to aggressive supportive treatment, including intubation, activated charcoal, and bicarbonate infusion, and fully recovered.
Learning Points:
NSAID overdose can cause severe metabolic acidosis by impairing mitochondrial function.
Lactic acidosis is a significant consequence of mitochondrial dysfunction in drug toxicity.
Timely intervention with activated charcoal and bicarbonate therapy can be life-saving in severe cases of drug overdose.
Monitoring and aggressive management of electrolyte imbalances and acid-base disturbances are critical in the treatment of overdose patients.
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Authors:
Bio:
Dr. Omid Mehrpour is a distinguished medical toxicologist known for his extensive clinical and research expertise. He focuses on understanding and treating toxic exposures. Renowned for his ability to diagnose and manage poisoning cases, Dr. Mehrpour has authored numerous impactful publications and is dedicated to educating future medical toxicologists. His innovative approach and commitment to patient care make him a leading figure in medical toxicology.
References:
Sandoval-Acuña, C., López-Alarcón, C., Aliaga, M., & Speisky, H. (2012). Inhibition of mitochondrial complex I by various non-steroidal anti-inflammatory drugs and its protection by quercetin via a coenzyme Q-like action.. Chemico-biological interactions, 199 1, 18-28 https://doi.org/10.1016/j.cbi.2012.05.006.
Emoto, A., Ushigome, F., Koyabu, N., Kajiya, H., Okabe, K., Satoh, S., Tsukimori, K., Nakano, H., Ohtani, H., & Sawada, Y. (2002). H(+)-linked transport of salicylic acid, an NSAID, in the human trophoblast cell line BeWo.. American journal of physiology. Cell physiology, 282 5, C1064-75. https://doi.org/10.1152/AJPCELL.00179.2001.
Shah, A., Wood, D., & Dargan, P. (2011). Understanding lactic acidosis in paracetamol (acetaminophen) poisoning.. British journal of clinical pharmacology, 71 1, 20-8 . https://doi.org/10.1111/j.1365-2125.2010.03765.x.
