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Hypotension and cardiac arrhythmias associated with widened QRS intervals on the ECG in a patient with thioridazine poisoning may respond to intravenous sodium bicarbonate as used for tricyclic antidepressants Prolongation of the QT interval and torsades de pointes is usually treated with intravenous magnesium or overdrive pacing For extrapyramidal signs, give diphenhydramine, 05 1 mg/kg intravenously, or benztropine mesylate, 001 002 mg/ kg intramuscularly Treatment with oral doses of these agents should be continued for 24 48 hours Bromocriptine (25 75 mg orally daily) may be effective for mild or moderate neuroleptic malignant syndrome Dantrolene (2 5 mg/kg intravenously) has also been used for muscle contractions but is not a true antidote
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Davis LE et al Persistent choreoathetosis in a fatal olanzapine overdose: drug kinetics, neuroimaging, and neuropathology Am J Psychiatry 2005 Jan;162(1):28 33 [PMID: 15625197]
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Salicylates (aspirin, methyl salicylate, etc) are found in a variety of over-the-counter and prescription medications Salicylates uncouple cellular oxidative phosphorylation, resulting in anaerobic metabolism and excessive production of lactic acid and heat, and they also interfere with several Krebs cycle enzymes A single ingestion of more than 200 mg/kg of salicylate is likely to produce significant acute intoxication Poisoning may also occur as a result of chronic excessive dosing over several days Although the half-life of salicylate is 2 3 hours after small doses, it may increase to 20 hours or more in patients with intoxication
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Acute ingestion often causes nausea and vomiting, occasionally with gastritis Moderate intoxication is characterized by hyperpnea (deep and rapid breathing), tachycardia, tinnitus, and elevated anion gap metabolic acidosis Serious intoxication may result in agitation, confusion, coma, seizures, cardiovascular collapse, pulmonary edema, hyperthermia, and death The prothrombin time is often elevated owing to salicylate-induced hypoprothrombinemia Diagnosis is suspected in any patient with metabolic acidosis and is confirmed by measuring the serum salicylate level Patients with levels greater than 100 mg/dL (1000 mg/L) after an acute overdose are more likely to have severe poisoning On the other hand, patients with subacute or chronic intoxication may suffer severe symptoms with levels of only 60 70 mg/dL The arterial blood gas typically reveals a respiratory alkalosis with an underlying metabolic acidosis
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Alkalinization of the urine enhances renal salicylate excretion by trapping the salicylate anion in the urine Add 100 mEq (two ampules) of sodium bicarbonate to 1 L of 5% dextrose in 02% saline, and infuse this solution intravenously at a rate of about 150 200 mL/h Unless the patient is oliguric, add 20 30 mEq of potassium chloride to each liter of intravenous fluid Patients who are volume-depleted often fail to produce an alkaline urine (paradoxical aciduria) unless potassium is given Hemodialysis may be lifesaving and is indicated for patients with severe metabolic acidosis, markedly altered mental status, or significantly elevated salicylate levels (eg, > 100 120 mg/dL [1000 1200 mg/L] after acute overdose or > 60 70 mg/dL [600 700 mg/L] with subacute or chronic intoxication)
Davis JE Are one or two dangerous Methyl salicylate exposure in toddlers J Emerg Med 2007 Jan;32(1):63 9 [PMID: 17239735] Graham CA et al Paracetamol and salicylate testing: routinely required for all overdose patients Eur J Emerg Med 2006 Feb;13(1):26 8 [PMID: 16374244] Rivera W et al Delayed salicylate toxicity at 35 hours without early manifestations following a single salicylate ingestion Ann Pharmacother 2004 Jul Aug;38(7 8):1186 8 [PMID: 15173556]
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Administer activated charcoal (see p 1362) Gastric lavage followed by administration of extra doses of activated charcoal may be needed in patients who ingest more than 10 g of aspirin (see p 1362) The desired ratio of charcoal to aspirin is about 10:1 by weight; while this cannot always be given as a single dose, it may be administered over the first 24 hours in divided doses every 2 4 hours Treat metabolic acidosis with intravenous sodium bicarbonate This is critical because acidosis (especially acidemia, pH < 740) promotes greater entry of salicylate into cells, worsening toxicity Brief hypoventilation during rapid sequence intubation may cause sudden and severe deterioration if the pH is allowed to fall
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