For salicylate overdose

Treatment. Serial measurements of plasma salicylate are necessary to monitor the course of the overdose, for the concentration may rise over the early hours after ingestion. The general management measures described in Chapter 9 apply, but the following are relevant for salicylate overdose. 

Alkallnizatlon is commonly used for salicylate overdose, but forced diuresis (producing urine volumes of up to 1 L/h) Is generally not used because of the risk of fluid overload. 

Screening for salicylates Overdoses of aspirin and other mild analgesics are extremely common. Salicylate is commonly detected in urine by the classical violet iron(III)-salicylate chelate formation. 

Sodium bicarbonate administration for cardiac arrest is controversial because there are few clinical data supporting its use, and it may have some detrimental effects. Sodium bicarbonate can be used in special circumstances (i.e., underlying metabolic acidosis, hyperkalemia, salicylate overdose, or tricyclic antidepressant overdose). The dosage should be guided by laboratory analysis if possible. 

Previously popular but of unproved value, forced diuresis may cause volume overload and electrolyte abnormalities and is not recommended. Renal elimination of a few toxins can be enhanced by alteration of urinary pH. For example, urinary alkalinization is useful in cases of salicylate overdose. Acidification may increase the urine concentration of drugs such as phencyclidine and amphetamines but is not advised because it may worsen renal complications from rhabdomyolysis, which often accompanies the intoxication. 

Brubacher JR, Pursseh R, Kent DA. Salty broth for salicylate poisoning Adequacy of overdose management... 

In salicylate poisoning, failure lo dclccl a large overdose early leads lo severe melabolic acidosis from which the patient may not recover. It is therefore important to exclude this common drug if there is any likelihood that it has been taken. A simple ijualitative lest is available in all hospitals with acute admissions. The treatment for salicylate poisttning is sodium bicarbonate, which both enhances excretion and helps correct the acidosis (Fig. 2). 

Certain cases of overdosage or iJoisoning. The mechanism common to all of these is the production of acid metabolites, for example in. salicylate overdose where build-up of lactate occurs, or methanol poisoning when formate accumulates, or ethylene glycol poisoning where oxalate is formed. 

Forced diuresis is occasionally useful. It may cause volume overload or electrolyte disturbances. Forced diuresis is useful for phenobarbital, bromides, lithium, salicylate, or amphetamines overdoses. Do not use for tricyclic antidepressants, sedative-hypnotics, or highly protein-bound medications. The most common agents employed are furosemide and osmotic diuretics with mannitol. 

Changes in plasma pH may also affect the distribution of toxic compounds by altering the proportion of the substance in the nonionized form, which will cause movement of the compound into or out of tissues. This may be of particular importance in the treatment of salicylate poisoning (see chap. 7) and barbiturate poisoning, for instance. Thus, the distribution of phenobarbital, a weak acid (pKa 7.2), shifts between the brain and other tissues and the plasma, with changes in plasma pH (Fig. 3.22). Consequently, the depth of anesthesia varies depending on the amount of phenobarbital in the brain. Alkalosis, which increases plasma pH, causes plasma phenobarbital to become more ionized, alters the equilibrium between plasma and brain, and causes phenobarbital to diffuse back into the plasma (Fig. 3.22). Acidosis will cause the opposite shift in distribution. Administration of bicarbonate is therefore used to treat overdoses of phenobarbital. This treatment will also cause alkaline diuresis and therefore facilitate excretion of phenobarbital into the urine (see below). 

Both accidental and intentional overdose are relatively frequent and pose difficult management problems. Particular concern has been expressed for children, either because they gain access to parents tablets or have been treated for enuresis. During one year a Melbourne hospital admitted 35 children poisoned with tricyclic antidepressants (147). In 1979 it was reported that tricyclic antidepressants had replaced salicylates as the most common cause of accidental death in English children under the age of five. Concern was expressed about this (148), and Swiss federal statistics raised similar worries (149). 

Such information is clinically useful. Consider drug overdose. Removing a drug by haemodialysis is likely to be a beneficial exercise oifly if a major proportion of the total body load is in the plasma, e.g. with salicylate which has a small distribution volume but haemodialysis is an inappropriate treatment for overdose with dothiepin which has a large distribution volume. These, however, are generalisations and if the knowledge of distribution volume is to be of practical value it must be quantified more precisely. 

Aspirin absorption may be delayed when overdose quantities are consumed, especially of enteric-coated or slow-release preparations. This must be considered when interpreting serum salicylate values, especially for specimens obtained earlier than 6 hours after ingestion. Repeat testing within 2 to 3 hours is recommended to ensure that absorption is complete subsequent testing provides an indication of effectiveness of therapeutic intervention. Because of the aforementioned complications, proper assessment of salicylate intoxication requires sound clinical evaluation in combination with serum salicylate levels. 

Drugs for which concentration assays are clearly unsuited include acute therapies (i.e. not used at steady state), those with extraordinarily short half-times (e.g. injected or intranasal polypeptides) and those for which either treatment is indicated regardless (late acetaminophen/parace-tamol overdoses, see above), or when adverse events are almost automatic and should be monitored in other ways, for example CNS toxicity with salicylates (see above) or liability to bone marrow suppression with cytotoxic agents. Furthermore, the efficacy and tolerability of some drugs are known to be unrelated to circulating concentrations (e.g. penicillin anaphylaxis),... 

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