Intoxicación por ácido acetilsalicílico, fisiopatología y manejo / Physiopathology and management of acetylsalicylic acid intoxication

Acetylsalicylic acid (ASA) intoxication is potentially lethal. After ingestion, AAS is rapidly transformed into salicylic acid that dissociates into an hydrogen ion plus salicylate. Salicylate is the main form of AAS in the body and produces multiple alterations. Initially, the stimulation of the ventilatory center promotes a respiratory alkalosis. Then, the mitochondrial dysfunction induced by salicylate, will generate a progressive metabolic acidosis due to the accumulation of ketoacids, lactic acid and dicarboxylic acids among others. Another alterations include hydro electrolytic disorders, gastrointestinal lesions, neurological involvement, ototoxicity and coagulopathy. The correct handling of acetylsalicylic acid intoxication requires an thorough knowledge of its pharmacokinetics and pharmacodynamics. Treatment consists in life support measures, gastric lavage, activated charcoal and urinary alkalization to promote the excretion of salicylates. In some occasions, it will be necessary to start renal replacement therapy as soon as possible.

Intentional overdose with tinzaparin: management dilemmas.

BACKGROUND: Low-molecular-weight heparin (LMWH) is increasingly being prescribed for prophylaxis and treatment of thromboembolic diseases. Despite the fact that its therapeutic use is considered to be safe, it can be complicated by major hemorrhage and, in contrast to unfractionated heparin, it can only partially be neutralized by protamine. Recent reports of LMWH overdose illustrate the need for a consensus on its management. OBJECTIVES: To describe a case of self-poisoning with a very large dose of tinzaparin and discuss management options in patients with LMWH overdose. CASE REPORT: A 69-year-old woman was brought to the Emergency Department 2 h after injecting herself with 280,000 IU of tinzaparin subcutaneously in an attempt to commit suicide. Despite an unrecordable activated partial thromboplastin time (APTT > 180 s) and prolonged prothrombin time, there was no evidence of active bleeding. She was given an intravenous infusion of 100 mg protamine sulfate and was admitted to the intensive care unit, where further infusions of protamine were administered. Normalization of the APTT occurred 40-50 h post admission, reflecting normal tinzaparin clearance rather than neutralization by protamine. No hemorrhagic complications occurred during her hospitalization except for prolonged bleeding from venipuncture sites. CONCLUSION: In this case of massive tinzaparin overdose, conventional doses of protamine failed to rapidly normalize the deranged coagulation parameters. The favorable clinical outcome suggests that, regardless of the LMWH amount injected, no active treatment is needed in the absence of hemorrhage. This is in accordance with the limited published data concerning cases of overdose with other LMWHs.