Paracetamol overdose

Author Information

An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

• * Drug overdose

A 27-year-old woman developed acute liver failure and acute kidney injury following an overdose of paracetamol [time to reactions onsets not stated].

The woman with a remote history of focal segmental glomerular sclerosis, presented at an emergency department due to nausea, vomiting and abdominal pain radiating to the chest for 2 weeks. To manage the pain, she had ingested >50 tablets of paracetamol [acetaminophen; dosage not stated] over 3–4 days prior to the presentation. In the emergency department, she was haemodynamically stable except for mild tachycardia. Her BP was 135/85mm Hg and HR was 104 beats/minute. Her body temperature was found to be normal. She did not have tachypnoea. Her oxygen saturation was 100% on room air. She had generalised abdominal tenderness. Her cardiac and pulmonary examination were found to normal. Her mental status and neurological exam were intact upon presentation. Investigations revealed leukocytosis and elevated aminotransferases (elevated levels of AST and ALT). Her total bilirubin was 2.9 mg/dL, ALP was 97 U/L and INR was 1.7. She had a mild acute kidney injury with a creatinine of 1.04 mg/dL (baseline of 0.8 mg/dL). Lactate was 12.9 mEq/L and D-dimer was 21830 ng/mL. Paracetamol level was found to be elevated. Her chest x-ray was found to be normal. An abdominal and pelvic CT scan demonstrated diffuse colonic wall thickening most pronounced in the cecum, ascending and sigmoid colon. There was no evidence of hepatic steatosis on imaging. A COVID-19 nasopharyngeal swab was obtained in view of diarrhoea and abdominal pain and was found to be positive. Despite positive test, she did not have respiratory symptoms at the time of presentation. She received treatment with N-acetylcysteine. She was shifted to the ICU for further management and close monitoring of acute liver injury secondary to paracetamol overdose and COVID-19. Testing of acute viral hepatitis was found to be negative. Additionally, serological testing for autoimmune and genetic etiologies of liver disease were found to be negative. Two days after the admission, her hepatic synthetic function significantly worsened. Her total bilirubin increased to 4.3 mg/dL and INR increased to 6.3. Additionally, her aminotransferases (AST and ALT levels) were found to be elevated further. Her kidney function worsened, and she became oliguric. Later that day, frequent neurological examinations showed progressive changes in her mental status and she met criteria for acute liver failure which was attributed to paracetamol overdose. Hepatic encephalopathy eventually progressed to grade 3 of West Haven Grading system. An urgent CT brain showed diffusely small cerebral sulci and basal cisterns concerning for brain swelling. Arterial ammonia was 196 µmol/L and she was started on replacement therapy and eventually required intubation for airway protection. Neurology and neurosurgery were consulted, and it was decided to proceed with placement of a right frontal intracranial pressure monitor. Increased intracranial pressure was treated with 3% hypertonic saline for a sodium goal between 145 and 155 mmol/L, and supportive measures [details not stated]. She retained all brainstem reflexes. She required high-dose vasopressors [specific drug not stated] for undifferentiated shock, as she had normal cardiac function (ejection fraction 64%) and negative infectious work-up. An emergent liver transplant was initiated. Her interleukin 6 level was 131.3 pg/L. She was also found to have absolute lymphocytopenia, thrombocytopenia and hypoalbuminaemia. A CT scan of the chest was performed to evaluate the lung parenchyma in the setting of possible COVID-19. While imaging did not demonstrate interstitial lung disease, mild pneumomediastinum predominantly involving the posterior mediastinum was found and was most prominent around the oesophagus and left mainstem bronchus. Of note, imaging was obtained shortly prior to intubation and pneumomediastinum was attributed possibly to an esophageal microperforation secondary to vomiting. She was started on broad-spectrum antimicrobials [specific drug not stated] and further investigations of pneumomediastinum were held as she was eventually intubated and developed brain oedema. Repeat COVID-19 testing 2 days after the initial test was found to be negative. She was evaluated by anaesthesia, psychiatry, pharmacy, nutrition and the transplant social worker in addition to transplant hepatology and surgery. Given her initial high vasopressor requirements making her unsuitable for OLT, she underwent high-volume plasma exchange using 100% plasma replacement and completed two high-volume plasma exchange treatments as a bridge to liver transplantation. Following the first high-volume plasma exchange, her vasopressor requirements improved to minimal doses, and her prothrombin time/INR corrected to 1.2, enabling further evaluation for liver transplant candidacy. After multi-disciplinary discussions including transplant hepatology, transplant surgery, infectious diseases, psychiatry, transplant social worker, pharmacy, nutrition and anesthesia, her initial positive COVID-19 test was thought to be residual viral load. She was considered suitable for an orthotopic liver transplant.

The woman underwent a successful liver transplant. The liver transplant was complicated by hypotension, bradycardia with junctional rhythm and rise in intracranial pressure prior to native liver explantation, leading to significant ST-elevation on ECG concerning for an ST-elevation myocardial infarction. ECG changes largely resolved after reperfusion. Cold ischaemic time was 7 hours 19 minutes and warm ischaemic time was 29 minutes. Intraoperative estimated blood loss was 5L and she received 5 units of packed RBCs, 1 unit of platelets, 10 units of cryoprecipitates and 750mL of autotransfusion via CellSaver. Thromboelastography was used to trend coagulopathy during surgery. Pathology revealed hepatic parenchyma with extensive (>95%) centrilobular necrosis suggestive of paracetamol toxicity. There was no significant steatosis. She was transferred to the surgical intensive care unit following the liver transplant and was started on tacrolimus and a steroid taper [specific drug not stated] for immunosuppression, as she was deemed not to have an active COVID-19 infection. She initially continued to have intermittent spikes in intracranial pressure on postoperative days 1 and 2. The intracranial pressure monitor was removed on day 3 after the liver transplant and vasopressors were stopped. Her neurological status returned to baseline. She received COVID-19 convalescent plasma on postoperative day 1 given the severity of her illness. Her hepatic function tests continued to improve following the liver transplant. Her total bilirubin and INR normalised. An ECG was obtained postoperatively and was normal. A repeat echocardiogram revealed anormal cardiac function. She was extubated 5 days after the operation and transferred to a regular nursing floor. Repeat CT scan of the chest demonstrated resolution of previously observed pneumomediastinum. A third COVID test 6 days after the liver transplant was found to be negative. She underwent closure of fascia 10 days postoperatively. Days later, an abdominal CT revealed abdominal wall haematomas requiring haematoma evacuation in the operating room. She continued to improve and was discharged 27 days post-liver transplant in a good condition.