Treatment of ibuprofen intoxication in a dog via therapeutic plasma exchange.

OBJECTIVE: To describe the treatment of ibuprofen intoxication with therapeutic plasma exchange in a dog (TPE). SUMMARY: A 13-year-old male neutered mixed breed dog presented after ingesting approximately 200 mg/kg of ibuprofen. Treatment consisted of supportive medical therapy with IV fluids, gastrointestinal protectants, antiemetics and prostaglandin analogs, and TPE. A cycle of TPE was performed over 180 minutes, achieving 1.5 plasma volume exchanges. During therapy, heparinized blood and effluent samples were collected. Ibuprofen concentrations were determined in the samples by high-pressure liquid chromatography. Post TPE, the dog was continued on supportive medical therapy and was discharged 96 hours after the overdose. NEW OR UNIQUE INFORMATION: This report describes the use of TPE as an adjunct for ibuprofen intoxication. An 85% reduction in plasma ibuprofen concentration occurred and recovery from a potentially lethal ingestion of ibuprofen was achieved with TPE and supportive care. TPE should be considered when presented with acute ibuprofen intoxication due to the rapid and efficacious nature of therapy.

Central nervous system toxicity of mefenamic acid overdose compared with other NSAIDs: an analysis of cases reported to the United Kingdom National Poisons Information Service.

AIMS: Case reports and small case series suggest increased central nervous system (CNS) toxicity, especially convulsions, after overdose of mefenamic acid, compared with other nonsteroidal anti-inflammatory drugs (NSAIDs), although comparative epidemiological studies have not been conducted. The current study compared rates of CNS toxicity after overdose between mefenamic acid, ibuprofen, diclofenac and naproxen, as reported in telephone enquiries to the UK National Poisons Information Service (NPIS). METHODS: NPIS telephone enquiries related to the four NSAIDs, received between January 2007 and December 2013, were analysed, comparing the frequency of reported CNS toxicity (convulsions, altered conscious level, agitation or aggression, confusion or disorientation) using multivariable logistic regression. RESULTS: Of 22 937 patient-specific telephone enquiries, 10 398 did not involve co-ingestion of other substances (mefenamic acid 461, ibuprofen 8090, diclofenac 1300, naproxen 547). Patients taking mefenamic acid were younger and more commonly female than those using other NSAIDs. Those ingesting mefenamic acid were more likely to experience CNS toxicity than those ingesting the other NSAIDs combined [adjusted odds ratio (OR) 7.77, 95% confidence interval (CI) 5.68, 10.62], especially convulsions (adjusted OR 81.5, 95% CI 27.8, 238.8). Predictors of CNS toxicity included reported dose and age, but not gender. CONCLUSIONS: Mefenamic acid overdose is associated with a much larger and dose-related risk of CNS toxicity, especially convulsions, compared with overdose of other NSAIDs. The benefit-risk profile of mefenamic acid should now be re-evaluated in light of effective and less toxic alternatives.

Treatment of ibuprofen toxicity with serial charcoal hemoperfusion and hemodialysis in a dog.

OBJECTIVE: To describe the efficacy of serial charcoal hemoperfusion and hemodialysis in removing ibuprofen from a dog with severe clinical signs of toxicity. CASE SUMMARY: A dog ingested a minimum of 2,200 mg/kg of ibuprofen resulting in progressive neurologic dysfunction that progressed to a comatose state by the time of presentation. Extracorporeal charcoal hemoperfusion coupled serially with hemodialysis was performed to remove ibuprofen from this patient. Serial charcoal hemoperfusion and hemodialysis therapy resulted in complete reversal of the neurologic dysfunction in this dog. No evidence of acute kidney or hepatic injury was observed. Serum ibuprofen concentrations confirmed the efficacy of this treatment. NEW INFORMATION PROVIDED: This report details the technique for extracorporeal extraction of ibuprofen, a methodology that could be employed for other toxicities due to substances with similar pharmacokinetics. Complications and limitations (eg, saturation of the charcoal cartridge) of the therapy are discussed.

Massive acetaminophen overdose: effect of hemodialysis on acetaminophen and acetylcysteine kinetics.

CONTEXT: Early onset acidosis from mitochondrial toxicity can be observed in massive acetaminophen poisoning prior to the development of hepatotoxicity. In this context, the efficacy of acetylcysteine to reverse mitochondrial toxicity remains unclear and hemodialysis may offer prompt correction of acidosis. Unfortunately, toxicokinetics of acetaminophen and acetylcysteine during extracorporeal treatments hemodialysis have seldom been described. CASE DETAILS: An 18-year-old woman presented to the emergency department 60 minutes after ingestion of 100 g of acetaminophen, and unknown amounts of ibuprofen and ethanol. Initial assessment revealed an agitated patient. Her mental status worsened and she required intubation for airway protection. Investigations showed metabolic acidosis with lactate peaking at 8.6 mmol/L. Liver and coagulation profiles remained normal. Acetaminophen concentration peaked at 981 µg/ml (6496 µmol/L). Pending hemodialysis, the patient received 100 g of activated charcoal and an acetylcysteine infusion at 150 mg/kg over 1 hour, followed by 12.5 mg/kg/h for 4 hours. During hemodialysis, the infusion was maintained at 12.5 mg/kg/h to compensate for expected removal before it was decreased to 6.25 mg/kg for 20 hours after hemodialysis. The patient rapidly improved during hemodialysis and was discharged 48 hours post-admission. TOXICOKINETICS: The acetaminophen elimination half-life was 5.2 hours prior to hemodialysis, 1.9-hours during hemodialysis and 3.6 hours post hemodialysis. The acetaminophen and acetylcysteine clearances by A-V gradient during hemodialysis were 160.4 ml/min and 190.3 ml/min, respectively. Hemodialysis removed a total of 20.6 g of acetaminophen and 17.9 g of acetylcysteine. CONCLUSION: This study confirms the high dialyzability of both acetaminophen and acetylcysteine. Hemodialysis appears to be a beneficial therapeutic option in cases of massive acetaminophen ingestion with coma and lactic acidosis. Additionally, these results suggest that the infusion rate of acetylcysteine must be more than double during hemodialysis to compensate for its ongoing removal and provide similar plasma concentrations to the usual acetylcysteine regimen.

Medication-induced Takotsubo Cardiomyopathy presenting with cardiogenic shock-utility of extracorporeal membrane oxygenation (ECMO): case report and review of the literature.

Takotsubo cardiomyopathy (TTC) is a transient condition that affects the myocardium and is seen mostly in post-menopausal women secondary to an emotional or physical stressor; however, certain drugs have been described as cause of this syndrome. We report the case of a young female with medication--induced TTC, who presented with cardiogenic shock as initial manifestation, treated successfully with extracorporeal membrane oxygenation (ECMO). To our knowledge, this is the first case in the literature describing the use of ECMO in cardiogenic shock due to medication-induced TTC.

Intentional overdose of azathioprine in a patient with systemic lupus erythematosus.

A 14-year-old girl with systemic lupus erythematosus presented with a mixed overdose of paracetamol, ibuprofen and azathioprine (1500 mg) following a deliberate self-harm attempt. The patient was admitted and monitored. No adverse effects were observed. A review of the literature showed very few reported azathioprine overdoses. Lupus patients are at risk of developing low mood and depression (and related self-harm including overdose of medication). This can be as a consequence of the disease process itself or in reaction to the stresses of living with a chronic disease, which are perhaps particularly acute in some adolescents with the disease. An intentional overdose in a patient with lupus is clearly a cry for help and should be appropriately managed. Counselling of young people and their parents about possible mood disorders is an important part of the management of this chronic disease. Despite the theoretical risk of significant myelosuppression as well as other potential adverse effects, azathioprine in acute overdose seems to be generally well tolerated.

Acute Ibuprofen intoxication: report on a case and review of the literature.

A fatality following the ingestion of ibuprofen is reported. Ibuprofen is a prototypical nonsteroidal anti-inflammatory drug widely prescribed as an analgesic, anti-inflammatory, and antipyretic agent. To date, there are few case reports of fatal overdose with ibuprofen, following ibuprofen self-poisoning or accidental overdose. We report the case of a 51-year-old man with medical history of psychiatric disease, who was brought to the emergency department by ambulance with a chief complaint of having taken large amounts of drugs in a suicide attempt.Multiple empty containers of medications (ibuprofen, meloxicam, celecoxib, risperidone, citalopram, ketorolac, bromazepam) were found at the scene. He died 4 hours after admission to the emergency department, despite vigorous supportive care. Toxicological analyses were performed using a gas chromatography/mass spectrometry technique. The estimated ibuprofen concentration in the plasma was 600 µg/mL; gastric content was 200 µg/mL for this compound. Our report describes results of the forensic investigation and discuss the review of the literature.

Profound hypokalaemia due to Nurofen Plus and Red Bull misuse.

We report an unusual and emerging cause of profound hypokalaemia associated with a severe myopathy, attributable to misuse of Nurofen Plus, a readily available over-the-counter medication containing ibuprofen and codeine, and excessive ingestion of the caffeine-containing energy drink, Red Bull. The mechanism of the hypokalaemia may be ascribed to ibuprofen-mediated type 2 renal tubular acidosis, and caffeine-mediated antagonism of adenosine receptors or intercompartmental shift of potassium into the intracellular space. Practitioners should be aware that patients with codeine addiction who misuse Nurofen Plus may present with severe hypokalaemia complicated by myopathy.

Polyuria, acidosis, and coma following massive ibuprofen ingestion.

Ibuprofen was the first over-the-counter nonsteroidal anti-inflammatory drug available in the United States. Despite being a common agent of ingestion, significant toxicity in overdose is rare. We report a case of a massive ibuprofen ingestion who developed polyuria, acidosis, and coma but survived, despite having a serum ibuprofen concentration greater than previous fatal cases. A 19-year-old man ingested 90 g (1,200 mg/kg) ibuprofen. He was initially awake and alert, but his level of consciousness deteriorated over several hours. Seven hours following the ingestion, he was intubated and mechanically ventilated secondary to loss of airway reflexes. He developed a lactic acidosis and polyuria, which lasted for nearly 24 h. His serum creatinine peaked at 1.12 mg/dL. An ibuprofen level drawn 7 h postingestion was 739.2 mg/L (therapeutic 5-49 mg/L). We describe a case of a massive ibuprofen overdose characterized by metabolic acidosis, coma, and a state of high urine output who survived with aggressive supportive care. This case is unique in several ways. First, ibuprofen levels this high have only rarely been described. Second, polyuria is very poorly described following ibuprofen ingestions.

Is the intra-aortic balloon pump a method of brain protection during cardiogenic shock after drug intoxication?

Cardiovascular medications are ubiquitous and are frequently implicated in accidental or intentional overdose. It is common that combined use of these drugs may lead to hypotension and even shock, followed by metabolic derangements. We report a case in which an intra-aortic balloon pump (IABP) was used in the management of self-poisoning with verapamil, amlodipine, metoprolol, and ibuprofen. In presenting this case of combined massive drug ingestion, we outline early strategy in the Emergency Department and some alternative treatment options. Beyond pharmacological and conservative procedures, we implemented an invasive approach that included temporary pacing, mechanical ventilation, and intra-aortic balloon counterpulsation (IABP). Such intense treatment was necessary due to the critical state of the patient. In our opinion, the use of the IABP contributed to the final recovery of our adolescent patient. Combined mechanical and pharmacological treatment may protect from multi-organ insufficiency, including permanent central nervous system injury. It is hoped that reporting our experience will raise awareness of alternative treatment options for ingestions of cardiovascular medications.