Severe poisoning with naproxen causing coagulopathy.

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known for their most frequent side effects (digestive, renal and metabolic disorders) but are lesser known for other effects, such as coagulation disturbances. In this issue, we report the case of a 58-year-old woman who ingested 26 g of naproxen in a suicidal attempt and developed cardiovascular shock, hypocoagulability and thrombopenia. Her outcome was positive (extubation 3 days after admission [D3], correction of haemostatic disruptions on D5 and of thrombopenia on D6). Naproxen plasma concentration was at a toxic concentration of 1320 mg/L at 6 hours after drug ingestion. Only few cases of hypocoagulopathy are reported with the NSAIDs, and this is the first case that can be attributed to naproxen. A possible explanation of this phenomenon following naproxen ingestion is an inhibition of thromboxane A2, usually attributed to NSAIDs, combined with an inhibition of activation of downstream the cascade.

Refractory Hypotension Caused by Prazosin Overdose Combined With Acetaminophen and Naproxen Toxicity: A Case Report and Review of the Literature.

BACKGROUND: Pediatric exposure to prazosin is unusual because it is most commonly indicated for the treatment of hypertension. Prazosin's increase in popularity as a treatment for posttraumatic stress disorder makes it important for emergency physicians to be aware of how to manage potential toxic ingestion because of prazosin overdose. CASE REPORT: A 16-year-old, 76-kg female presented after ingesting 110 mg of prazosin, 209.3 g of acetaminophen, and 55 g of naproxen. She was admitted to the pediatric intensive care unit for rapidly deteriorating hypotension (lowest blood pressure 47/19 mm Hg) refractory to aggressive fluid resuscitation and infusions of epinephrine and norepinephrine each at 0.5 mcg/kg/min. Stabilization of blood pressure was eventually achieved, and associated with use of a vasopressin infusion of 0.004 units/kg/min. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Because of the increasing exposure of children to prazosin, clinicians should be aware of the pharmacology behind alpha-1 antagonist overdose and consider treatment options, such as vasopressin, when hypotension is resistant to standard fluid and catecholamine 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.

Massive naproxen overdose with serial serum levels.

CONTEXT: Massive naproxen overdose is not commonly reported. Severe metabolic acidosis and seizure have been described, but the use of renal replacement therapy has not been studied in the context of overdose. CASE DETAILS: A 28-year-old man ingested 70 g of naproxen along with an unknown amount of alcohol in a suicidal attempt. On examination in the emergency department 90 min later, he was drowsy but had normal vital signs apart from sinus tachycardia. Serum naproxen level 90 min after ingestion was 1,580 mg/L (therapeutic range 25-75 mg/L). He developed metabolic acidosis requiring renal replacement therapy using sustained low efficiency dialysis (SLED) and continuous venovenous hemofiltration (CVVH) and had recurrent seizure activity requiring intubation within 4 h from ingestion. He recovered after 48 h. DISCUSSION: Massive naproxen overdose can present with serious toxicity including seizures, altered mental status, and metabolic acidosis. CONCLUSION: Hemodialysis and renal replacement therapy may correct the acid base disturbance and provide support in cases of renal impairment in context of naproxen overdose, but further studies are needed to determine the extraction of naproxen.

Acute pancreatitis following naproxen intake.

Pancreatitis is a very rare complication of a few nonsteroidal anti-inflammatory drugs. In this paper, we report a 20-year-old male as a case of acute pancreatitis following a suicidal attempt with naproxen sodium. We believe that, in this case, the pancreatitis was another example of a rare adverse reaction to the intake of nonsteroidal anti-inflammatory drugs.

[Severe toxic liver failure after acute poisoning with paracetamol, ferrous sulphate and naproxen]. / Ciezkie toksyczne uszkodzenie watroby w zatruciu lekami mieszanymi--paracetamolem, siarczanem zelaza i naproksenem.

We present the case of 20-year-old woman intoxicated with mixed drugs, composed of paracetamol (acetaminophen), ferrous sulphate, naproxen and benzodiazepines. Acute toxic liver damage with clinical symptoms of coma resolved at the patient. Lack of the past history doesn't let to specific therapy and systemic complications. In this data we confirm, that past history, clinical symptoms and laboratory results are needed in designing a treatment strategy.

[Two complex suicidal poisonings with drugs and their medicolegal aspects]. / Dwa kompleksowe samobójcze zatrucia lekami w aspekcie orzecznictwa sadowo-lekarskiego.

The main subject of the study was a toxicological investigation of biological specimens coming from two cases of intoxication with mixture of drugs. Two young people decided to commit suicide by the use of mixture of drugs mainly analgesic in approximately equal doses. For one person the dose of drugs administered turned out to be fatal while second person survived with the symptoms of acute intoxication. The analysis carried out with the use of liquid chromatographic method with mass detection (HPLC/MS) confirmed the presence of mixture of drugs in blood of living person and in postmortem specimens of the victim in significant concentrations. The toxicological findings have delivered information for discussion in medico-legal and ethical aspects.

Pseudomethemoglobinemia: a case report and review of sulfhemoglobinemia.

OBJECTIVES: To see if methemoglobin could potentially be misdiagnosed and the limitation of present cooximeters. PATIENT: A 17-year-old girl who overingested a combination of cimetidine, acetaminophen, ibuprofen, and naproxen in a suicide attempt. METHOD: Use of pulse co-oximeters to aid in the diagnosis of suspected sulfhemoglobinemia. RESULTS: Diagnosis of sulfhemoglobinemia achieved with final confirmation made with gas chromatography. Patient steadily improved with supportive care. CONCLUSIONS: There is a potential for the diagnosis of methemoglobin with some of the limitations of present co-oximeters. The laboratory diagnosis of sulfhemoglobinemia can be difficult to make.

Triphasic waves associated with acute naproxen overdose: a case report.

Triphasic waves (TWs) can be recorded on EEG in the course of several metabolic disorders, mainly hepatic encephalopathy. A case of acute encephalopathy due to naproxen intoxication is reported, in the course of which diffuse, bilateral and symmetrical TWs were recorded. Biochemical mechanisms that might determine both a complex encephalopathy and TWs are discussed.

Acute nonoliguric renal failure in children associated with nonsteroidal antiinflammatory agents.

OBJECTIVE: Acute renal failure is commonly seen in adults after treatment with nonsteroidal antiinflammatory agents. This complication has rarely been reported in children. DESIGN: Four consecutive patients admitted with acute nonoliguric renal failure associated with ingestion of nonsteroidal antiinflammatory agents. SETTING: The emergency department and ward units at The Children's Hospital of Philadelphia. PATIENTS: Four patients, ages 3.5 to 19 years. INTERVENTIONS: Appropriate evaluations including measurement of serum creatinine concentrations in the emergency department and careful histories of drug ingestion. MAIN OUTCOME MEASURE: Rapid return to normal serum creatinine concentrations. RESULTS: Four patients were admitted to The Children's Hospital of Philadelphia between May 1996 and June 1997 with a diagnosis of acute, nonoliguric renal failure following ingestion of nonsteroidal antiinflammatory agents. None of the patients had features of hemolytic uremic syndrome, systemic lupus, dehydration, obstructive uropathy or sickle cell disease. Each patient had ingested nonsteroidal antiinflammatory agents before the onset of acute renal failure. None had oliguria or anuria, dehydration, abnormal serum electrolyte concentrations, or evidence of glomerulonephritis. One patient also had a urinary tract infection that was treated with antibiotics. Another patient was treated with methylprednisolone and prednisone. None was biopsied. Three recovered completely. CONCLUSION: With the increasing use of over-the-counter nonsteroidal antiinflammatory agents, this association may become more prevalent.

Naproxen toxicosis in a puppy.

Naproxen toxicosis is described in a puppy that had been given 220 mg of naproxen (ALLEVE) over a 4-d period. Clinical signs included melena, lethargy and vomiting. The puppy recovered with a blood transfusion (due to anemia), gastroprotective medications, and supportive care.

Renal impairment after acute diclofenac, naproxen, and sulindac overdoses.

Acute renal dysfunction has been described as a feature of acute overdoses of the nonsteroidal anti-inflammatory drugs benoxaprofen, fenoprofen, ibuprofen, mefenamic acid, piroxicam, suprofen, and zomepirac. The cases reported here include renal impairment after acute overdoses of another three nonsteroidal anti-inflammatory drugs: diclofenac (one case), naproxen (two cases), and sulindac (five cases). The eight patients presented with lumbar pain and oliguria and had protein and erythrocytes in the urine. Serum creatinine was increased to a maximum of 190-932 mumol/L. Renal impairment was generally transient but in one case was treated by hemodialysis and one by continuous arterio-venous hemofiltration dialysis. In all cases of significant acute overdose of nonsteroidal anti-inflammatory drugs, the risk of acute renal dysfunction must be considered.

Delayed toxic acetaminophen level after initial four hour nontoxic level.

Antidotal therapy for acetaminophen poisoning is routinely based on a single acetaminophen level obtained four or more hours after ingestion. Some experts recommend additional acetaminophen levels if there are coingestants. This case report describes a 20-year-old woman who ingested acetaminophen 13 g, propoxyphene napsylate 2 g and naproxen sodium 3.75 g. A 4.5 h acetaminophen level was 83.5 mg/L (nontoxic). A 6.75 h acetaminophen level was 124.6 mg/L (toxic). The patient was treated with N-acetylcysteine and recovered without sequelae. This is the first published report of a delayed toxic acetaminophen level occurring after an initial nontoxic level. Although rare, the possibility of a delayed peak acetaminophen level merits consideration, particularly with coingestions that delay gastric emptying.

[Fulminating hepatitis after treatment with naproxen and/or disulfiram?]. / Fulminant hepatitt etter behandling med naproxen og/eller disulfiram?

A 49 year old female was started on disulfiram. Six weeks later she was given naproxen because of epicondylitis. After 5 days' treatment with naproxen she complained of nausea, anorexia and jaundice. At admission, bilirubin was 452 mumol/l, aspartate aminotransferase (ASAT) 1925 U/I, alanine aminotransferase (ALAT) 2815 U/I and prothrombin time measured as Normotest was 27%. The patient developed a fulminant hepatitis and died in hepatic coma almost four weeks after the introduction of naproxen. Postmortem examination disclosed a small liver (1,100 g) and histological examination showed massive necrosis and collapse of the lobules. The naproxen was the most probable cause of death, but it is impossible to exclude disulfiram as causative agent.

Severe metabolic acidosis after acute naproxen sodium ingestion.

Naproxen, a nonsteroidal anti-inflammatory drug (NSAID), is a propionic acid derivative that possesses analgesic and antipyretic properties through inhibition of prostaglandin synthesis. The propionic acids have been considered the least toxic of the NSAIDs, and one, ibuprofen, is currently available as an over-the-counter medication. Though acidosis has been reported with ibuprofen, no such occurrence has been reported for naproxen sodium. We report the case of a 15-year-old girl who presented with severe metabolic acidosis and seizures that rapidly followed naproxen sodium ingestion. Serum bicarbonate levels returned to normal 12 hours after admission and correlated with the known pharmacokinetics of naproxen. The pharmacokinetics of naproxen and treatment of its overdose, and possible mechanisms of metabolic acidosis are reviewed.

Naproxen-induced toxicosis in a dog.

Naproxen, a nonsteroidal anti-inflammatory drug, induced gastric ulceration and bleeding in a dog. Clinical signs included vomiting, anemia, melena, and weakness. The dog responded to a blood transfusion and supportive treatment (lactated Ringer's solution with added K+ and B vitamins, an antacid, and cimetidine). Naproxen had been given to the dog by the owner, as treatment for shoulder stiffness.

Hypoprothrombinemia in naproxen overdose.

Transient prolongation of the prothrombin time was observed in the setting of a 10-g overdose of naproxen. The patient reported was previously healthy, without chronic liver disease, bleeding disorders, or malnutrition. The most likely mechanism for this effect is direct inhibition of the synthesis of vitamin-K-dependent clotting factors, possibly via production of "abnormal" prothrombin.