Massive intoxication with rivaroxaban, phenprocoumon, and diclofenac: A case report.

RATIONALE: Oral anticoagulants and painkillers, some with an additional effect on the coagulation system, are widely used and are therefore prone to abuse and (intentional) overdose. We report the case of a patient with a massive mixed anticoagulant intoxication. PATIENT CONCERNS: The patient had ingested 1960 mg rivaroxaban, 31.5 mg phenprocoumon, 1425 mg diclofenac, and 21,000 mg metamizole in suicidal intention. DIAGNOSES: Massive mixed anticoagulant overdose. INTERVENTIONS: The patient was closely monitored. The phenprocoumon overdose was treated by the administration of vitamin K and PCC. OUTCOMES: Despite the massive inhibition of the coagulation system, the patient did not experience bleeding apart from a slight gross hematuria. LESSONS: Despite the ingestion of a massive amount of rivaroxaban, the plasma levels were not as high as feared, due to the ceiling effect of rivaroxaban absorption. Elimination occurred according to the half-life of rivaroxaban and was not unduly prolonged by the ingested quantity.

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.

Hemodialysis and extracorporeal removal after pediatric and adolescent poisoning reported to a state poison center.

BACKGROUND: There is currently limited literature regarding the use of hemodialysis after acute pediatric and adolescent poisoning. OBJECTIVE: We sought to characterize the use of hemodialysis (HD) and other extracorporeal removal techniques (ECR) in the treatment of acutely poisoned children and adolescents reported to a state poison control system over a 10-year period. METHODS: After institutional review board approval, a state poison control system database was queried for all cases coded for hemodialysis and other ECR after pediatric and adolescent (0-19 years old) poisoning. We also analyzed National Poison System Data to determine national trends. RESULTS: Ninety patients were reviewed after exclusions for errors in coding or incomplete documentation. HD was the principle method of ECR employed. One case of hemoperfusion and hemofiltration was reported. HD was used, on average, nine times per year. ECR was used predominantly in adolescent patients (age ≥ to 12 years) (84 patients, 93%) for intentional ingestions (82 patients, 91%). Fifteen different toxins were encountered, with salicylates (29 patients) and ethylene glycol (23 patients) most commonly encountered. Ethylene glycol and methanol blood levels were not available before initiation of hemodialysis in all but one case. CONCLUSIONS: All salicylate-poisoned patients who underwent HD demonstrated clinical findings indicative of toxicity even in the absence of elevated levels advocated by some as indication for HD. HD and other ECR are rarely used in the management of pediatric and adolescent poisoning.

Coingestion of cyclooxygenase inhibitors can worsen severe paracetamol poisoning by middle-sized and small arteries vasoconstriction.

OBJECTIVE: We report fatal cases of multifocal ischemic injuries occurring in patients awaiting liver transplantation after severe concomitant paracetamol and cyclooygenase inhibitors self-poisoning. DESIGN AND SETTING: Case report in an intensive care unit. PATIENTS: In addition to signs of acute liver failure with a systemic inflammatory response syndrome, these three previously healthy young women demonstrated cutaneous vasoconstriction. One patient displayed a sudden ST-segment elevation with ventricular fibrillation. INTERVENTIONS: Angiography, plasma endothelin concentrations measurements, and autopsy. RESULTS: Radiography showed diffuse vasospasm on mesenteric and renal arteries, transiently reversed by vasodilators. We measured tenfold higher plasma endothelin concentrations than in healthy controls. Autopsy revealed no atherosis (including coronary arteries); organs showed multifocal ischemic injuries without thrombosis. CONCLUSIONS: Such injuries subsequent to dramatic vasoconstriction suggest that cyclooygenase inhibition has specific deleterious vascular side effects once systemic inflammatory response syndrome is in progress during paracetamol poisoning.

Mechanisms involved in the attenuation of intestinal toxicity induced by (S)-(+)-ketoprofen in re-fed rats.

In addition to suppression of prostaglandins synthesis a number of factors have been implicated in nonsteroidal antiinflammatory drugs (NSAIDs) enteropathy, including oxygen radical-dependent microvascular injuries, depletion of glutathione, and food. Inflammatory cytokines such as tumor necrosis factor-alpha regulate endothelial adhesion molecules expression and promote vascular neutrophil adherence. Racemic ketoprofen is a potent NSAID with a chiral structure existing in two enantiomeric forms. Its therapeutic effects reside almost exclusively in the (S)-(+) isomer nevertheless the potential contribution to side effects of the (R)-(-) isomer cannot be ignored. The aims of this study were to explore the role of prostaglandins depletion, tumor necrosis factor-alpha production, and glutathione homeostasis in the comparative pathogenesis of intestinal injury induced by racemic-ketoprofen and its enantiomers in re-fed rats. Racemic ketoprofen and (R)-(-)-ketoprofen dose-dependently caused similar and multiple lesions in the mid-jejunum significantly higher than those observed with (S)-(+)-ketoprofen. All the treatments significantly decreased prostaglandins content. A significant increase of tumor necrosis factor-alpha production and decreases in glutathione levels and glutathione reductase activity after treatment of the racemate and (R)-(-)-ketoprofen, were observed whereas the (S)-(+)-isomer did not change these parameters. In conclusion, (S)-(+)-ketoprofen possesses a better intestinal toxicity profile than the racemate and its (R)-(-)-isomer. Despite inhibiting cyclooxygenase activity, the attenuation of (S)-(+)-ketoprofen-induced intestinal toxicity could be correlated with a reduced oxidative damage characterized not only by a lack of changes in glutathione reductase activity and glutathione levels but also by an absence of up-regulation of tumor necrosis factor-alpha production in intestinal mucosa.

Oxidative damage on lymphocyte membranes is increased in patients suffering from acute carbon monoxide poisoning.

Increased oxidative damage seems to be a relevant mechanism in the pathophysiology of patients with an acute carbon monoxide (CO) poisoning. We have investigated the degree of membrane oxidative damage through the assessment of lipid peroxidation in circulating lymphocytes from five patients acutely intoxicated by CO. Since mitochondria are a major source of reactive oxygen species and mitochondrial cytochrome c oxidase (COX) has been reported to be inhibited after acute CO poisoning, we have also assessed the lymphocyte COX activity and its relationship with the degree of lipid peroxidation. Data were compared with those from 32 non-smoker healthy controls comparable in terms of age, gender and physical activity. In intoxicated patients, we have found a significant increase of lipid peroxidation compared to control individuals (P < 0.05), as well as a marked COX inhibition (P < 0.001). Both parameters showed a positive, nearly significant correlation (r = 0.81, P = 0.09). We conclude that oxidative damage of lymphocyte membranes is increased after acute CO poisoning, and suggest that such increase could be partially mediated by mitochondrial COX inhibition caused by CO.