Lactic acidosis and multisystem organ failure following ibuprofen overdose requiring haemodialysis

Background

Over 50 years ago, Stewart Adams and his colleagues discovered the anti-inflammatory effects of ibuprofen.1 Initially identified to aid in rheumatoid arthritis, it is now ubiquitous, sed for many aches and ailments. Ibuprofen was approved as a non-prescription over the counter drug in the USA in 1984.1 However, it did not come without caution; there were identified risks of gastrointestinal events (eg, ulcerations and/or bleeding) and cardiovascular events (eg, fatal and non-fatal myocardial infarctions), although primarily seen in rheumatological high doses (3–4 g/day) rather than standard therapeutic doses (<2400 mg/day).1

When ingested at supratherapeutic doses, the outcome of ibuprofen overdose can be fatal due to circulatory collapse and further multisystem organ failure (MSOF).2 3 We present a case of intentional drug ingestion of ibuprofen resulting in severe metabolic acidosis and MSOF. The use of continuous renal replacement therapy (CRRT) achieved metabolic stabilisation and reversal of severe haemodynamic instability.

Case presentation

A 17-year-old, 65 kg male patient, with a medical history significant for major depressive disorder, generalised anxiety and recent suicidal ideation, presented to the emergency department with altered mental status. He was found at home, lying on the floor with four open pill bottles on the counter. The bottles consisted of ibuprofen, naproxen and acetaminophen, which were partially consumed, and total amount taken could not be estimated. The fourth bottle was acetaminophen/hydrocodone, and was reported to only contained a few tablets which were presumed to have been consumed. He had also taken his prescribed medication at the recommended dose; trazodone and melatonin. The patient was last visualised in normal state of health 2 hours prior to being found.

The patient was transported by ambulance to the emergency department. On arrival, he was somnolent with dilated, but reactive pupils. Vital signs were temperature 36.3°C, heart rate 110 beats per minute, respiratory rate of 20 breaths per minute, blood pressure 107/57 mm Hg, with oxyhaemoglobin saturation measured via pulse oximetry of 97% in room air. Reflexes were intact, with normal muscle tone and no clonus. There was no evidence of self-induced trauma.

Investigations

A peripheral intravenous catheter was placed and standard labs, plasma drug levels and a urine drug screen, were obtained. Venous blood gas showed pH 7.23, Partial pressure carbon dioxide (PCO₂) 50 mm Hg, Bicarbonate (HCO₃) 21 mm Hg, lactate 1.4 mmol/L (reference range: pH 7.32–7.42, PCO₂ 41–51 mm Hg, HCO₃ 22–26 mm Hg, lactate 0.5–1.6 mmol/L). The presenting acetaminophen level was 34 ug/mL (therapeutic reference range: 10–30 µg/mL), and salicylate level was less than 3 mg/dL (therapeutic reference range: 2–30 mg/dL). His blood serum ethanol level was below the detectable limit. A urine drug screen and gas chromatography were evaluated and detected acetaminophen, ibuprofen and sertraline. All other laboratory findings were within normal limits including electrolytes, liver function tests and coagulation panel; specifically, urea nitrogen of 13 mg/dL and creatinine 1 mg/dL (reference range: urea nitrogen 8–20 mg/dL, creatinine 0.7–1.3 mg/dL). ECG showed sinus tachycardia, with a normal corrected QT interval.

Poison control was contacted and recommended a 4-hour acetaminophen level, which was 32 µg/mL and below the treatment nomogram. He received famotidine for gastrointestinal prophylaxis. A total of 2 L of normal saline were administered for resuscitation in the setting of intermittent hypotension. Due to his somnolence, a non-contrast head CT was completed, without evidence of intracranial bleeding or other acute intracranial processes. He did not receive activated charcoal as part of his treatment.

The patient was admitted to the paediatric intensive care unit for somnolence and close monitoring. In the first 23 hours of his hospitalisation (up to 25 hours following ingestion), his Glasgow Coma Scale (GCS) was 10. He opened his eyes spontaneously, did not follow commands, was lethargic and non-verbal. However, the patient maintained adequate respiratory effort, oxygenation and ventilation. During this time, his lactate levels remained between 2–4 mmol/L, creatinine between 1.0 and 1.06 mg/dL, and he maintained adequate urine output of 2.5 mL/kg/hour.

Treatment

Twenty-four hours following hospitalisation (26 hours following ingestion), the patient became less responsive, and lactate quickly increased from 4 to 12 mmol/L. His neurological status declined to a GCS of 7; eyes did not open to painful stimuli, he was confused, and had abnormal extension of his extremities. Additionally, no longer had a gag reflex, was not protecting his airway, subsequently his trachea was orally intubated. He developed persistent hypotension with systolic blood pressures of 80s mmHg, and a metabolic acidosis (pH 7.15, PCO2 28.5 mm Hg, HCO₃ 9.5 mm Hg). He received multiple doses of sodium bicarbonate without improvement in acidosis and hypotension. The patient required epinephrine (maximum dose 0.15 mcg/kg/min) and norepinephrine (maximum dose 0.1 mcg/kg/min) infusions for haemodynamic support. Central and arterial access was obtained for close monitoring, medication administration, and continued resuscitation. Another urine drug screen and gas chromatography obtained and this one detected acetaminophen, ibuprofen and naproxen.

Due to refractory metabolic acidosis (lactate level >24 mmol/L, definitive number not reportable by our lab) and MSOF, an acute dialysis catheter was inserted, with intent to gain metabolic stabilisation. He was initiated on CRRT in the 29th hour of hospitalisation (31 hours following ingestion). CRRT was started using a Prismaflex HF1000 filter, with a blood flow rate of 200 mL/min, and dialysate rate of 4000 mL/hour, roughly 4000 mL/1.73 m². Sodium bicarbonate infusion at 500 mL/hour (around 1 mEq/kg/hour) was used as a postfilter fluid replacement. Volume status was not altered, as CRRT provided clearance only and no fluid removal. Acidosis resolved over 10 hours following CRRT initiation, with a corresponding decrease in vasoactive support (figure 1). His creatinine remained stable at 0.96–1.15 mg/dL. After 28 hours of CRRT, the patient’s neurological status returned to baseline, and his trachea was extubated. CRRT was discontinued 43 hours after initiation. The patient had no further CRRT or intermittent haemodialysis requirements during hospitalisation.

Outcome and follow-up

On initial lab collection in the emergency department a serum ibuprofen level was obtained, and subsequently resulted 2 weeks following presentation at 841 µg/mL (therapeutic reference range: 10–50 µg/mL). Following medical stabilisation, approximately 157 hours (6.5 days) after admission, he was further treated at an inpatient psychiatric care centre.

Due to his acute kidney injury with need for CRRT, he continued to follow with outpatient nephrology. Blood pressure remained within normal limits for height and age and kidney function returned to his predialysis baseline. Following recovery, patient and guardian provided written informed consent for publication of this case review.