"Nov. 2, 2012 -- Safety steps taken in the wake of the fungal meningitis outbreak have worsened drug shortages, raising questions about whether the U.S. must choose between the safety and the availability of crucial medicines.
Severe intoxication, caused by overdose of aspirin and codeine, may produce: skin eruptions, dyspnea, vertigo, double vision, delusions, hallucinations, garbled speech, excitability, restlessness, delirium, constricted pupils, a positive Babinski sign, respiratory depression (slow and shallow breathing; Cheyne-Stokes respiration), cyanosis, clammy skin, muscle flaccidity, circulatory collapse, stupor and coma. In children, difficulty in hearing, tinnitus, dim vision, headache, dizziness, drowsiness, confusion, rapid breathing, sweating, thirst, nausea, vomiting, hyperpyrexia, dehydration and convulsions are prominent signs. The most severe manifestations from aspirin result from cardiovascular and respiratory insufficiency secondary to acid-base and electrolyte disturbances, complicated by hyperthermia and dehydration. The most severe manifestations from codeine are associated with respiratory depression.
Respiratory alkalosis is characteristic of the early phase of intoxication with aspirin while hyperventilation is occurring, but is quickly followed by metabolic acidosis in most people with severe intoxication. This occurs more readily in children. Hypoglycemia may occur in children who have taken large overdoses. Other laboratory findings associated with aspirin intoxication include ketonuria, hyponatremia, hypokalemia, and occasionally, proteinuria. A slight rise in lactic dehydrogenase and hydroxybutyric dehydrogenase may occur.
Concentrations of aspirin in plasma above 30 mg/100 mL are associated with toxicity. (See CLINICAL PHARMACOLOGY section for information on factors influencing aspirin blood levels.) The single lethal dose of aspirin in adults is probably about 25-30 g, but is not known with certainty.
The toxic plasma concentration of codeine is not known with certainty. Experimental production of mild to moderate CNS depression in healthy, nontolerant subjects occurred at plasma concentrations of 0.05-0.19 mg/100 mL when codeine was given by intravenous infusion. The single lethal dose of codeine in adults is estimated to be from 0.5-1.0 g. It is also estimated that 5 mg/kg could be fatal in children. Hemodialysis and peritoneal dialysis can be performed to reduce the body aspirin content. Codeine is theoretically dialyzable but the procedure has not been clinically established.
Treatment of overdosage consists primarily of support of vital functions, management of codeine-induced respiratory depression, increasing salicylate elimination, and correcting the acid-base imbalance due primarily to salicylism.
In a comatose patient, primary attention should be given to establishment of adequate respiratory exchange through provisions of a patent airway and the institution of assisted or controlled ventilation. The narcotic antagonist naloxone is a specific antidote for respiratory depression which may result from Overdose or unusual sensitivity to narcotics. Therefore, an appropriate dose of an antagonist should be administered, preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation. Since the duration of action of aspirin and codeine (aspirin and codeine (aspirin and codeine) ) may exceed that of the antagonist, the patient should be kept under continued surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. A narcotic antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.
Gastric emptying (Syrup of Ipecac) and/or lavage is recommended as soon as possible after ingestion, even if the patient has vomited spontaneously. (Apomorphine should not be used as an emetic for aspirin and codeine (aspirin and codeine (aspirin and codeine) ) , since it may potentiate hypotension and respiratory depression.) Administration of activated charcoal as a slurry is beneficial after lavage and or emesis, if less than three hours have passed since ingestion. Charcoal adsorption should not be employed prior to emesis or lavage.
Severity of aspirin intoxication is determined by measuring the blood salicylate level. Acid-base status should be closely followed with serial blood gas and serum pH measurements. Fluid and electrolyte balance should also be regularly monitored.
A serum salicylate level of 30 mg/100 mL or higher indicates a need for enhanced salicylate excretion that can be achieved through body-fluid supplementation and urine alkalinization if renal function is normal. In mild intoxication, urine flow can be increased by forcing oral fluids and giving potassium citrate capsules. (DO NOT GIVE BICARBONATE BY MOUTH SINCE IT INCREASES THE R.T. OF SALICYLATE ABSORPTION.)
In severe cases, hyperthermia and hypovolemia, as well as respiratory depression are the major immediate threats to life. Children should be sponged with tepid water. Replacement fluid should be administered intravenously and augmented with sufficient bicarbonate to correct acidosis, with monitoring of plasma electrolytes and pH, to promote alkaline diuresis of salicylate if renal function is normal. Complete control may also require infusion of glucose to control hypoglycemia. Potassium deficiency may also be corrected through the infusion, once adequate urinary output is assured. Plasma or plasma expanders may be needed if fluid replacement is insufficient to maintain normal blood pressure or adequate urinary output.
In patients with renal insufficiency or in cases of life-threatening intoxication, dialysis is usually required. Peritoneal dialysis or exchange-transfusion is indicated in infants and young children, and hemodialysis in older patients. Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as needed.
Aspirin and codeine (aspirin and codeine (aspirin and codeine) ) phosphate is contraindicated under the following conditions:
- (1) hypersensitivity or intolerance to aspirin or codeine,
- (2) severe bleeding, disorders of coagulation or primary hemostasis, including hemophilia, hypoprothrombinemia, von Willebrand†s disease, the thrombocytopenias, thrombasthenia and other ill-defined hereditary platelet dysfunctions, as well as such associated conditions as severe vitamin K deficiency and severe liver damage,
- (3) anticoagulant therapy, and
- (4) peptic ulcer, or other serious gastrointestinal lesions.
Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.
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