In this section only specific treatment regimens will be discussed. The general principles of management of selfpoisoning will always be required.
Analgesic poisoning is common in some areas, accounting for one-third of all cases of self-poisoning admitted to hospital. Salicylate poisoning has decreased over the past decade, while paracetamol poisoning has increased. Combinations of aspirin or paracetamol and narcotic analgesics such as codeine or dextropropoxyphene are frequently taken. Co-proxamol, a combination of paracetamol and dextropropoxyphene can cause severe respiratory depression and is a major cause of death. Accidental poisoning with analgesics has decreased since the introduction of child-resistant bottles.
Salicylates are well absorbed from the stomach and small intestine. They are metabolized to form salicyluric acid and salicyl phenolic glucuronides, a process that is saturated at therapeutic dosage. At high doses, renal excretion becomes important. Overdosage stimulates the respiratory centre, directly increasing the depth and rate of respiration and thereby producing a respiratory alkalosis. Compensatory mechanisms include renal excretion of bicarbonate and potassium, which results in a metabolic acidosis. Salicylates also interfere with carbohydrate, fat and protein metabolism, as well as with oxidative phosphorylation. This gives rise to increased lactate, pyruvate and ketone bodies, all of which contribute to the acidosis. Symptoms and signs of salicylate poisoning include tinnitus, nausea and vomiting, overbreathing, hyperpyrexia and sweating with a tachycardia. Alternatively, the patient may appear completely well, even with high blood levels of salicylate. The ingestion of 10-20 g of aspirin by an adult (or one-tenth of this amount for a child) is likely to cause moderate or severe toxicity.With severe intoxication (salicylate levels 800- 1000 mg litre:”: 5.6-7.2 mmol litre “), confusion delirium, convulsions and coma result. Coma is common in children. It should be remembered that consciousness is not impaired unless the blood salicylate level is very high or, more commonly, another drug has been taken. Cerebral and pulmonary oedema are serious complications, and may be exacerbated by forced diuresis.
Aspirin delays gastric emptying and gastric lavage should be performed up to 12 hours after the ingestion in all but the mildest cases and in severe cases up to 24 hours. Activated charcoal in repeated doses should be given. Intravenous fluids may be necessary to correct dehy dration and hypokalaemia. Occasionally intramuscular vitamin K is required to correct hypoprothrombinaemia. Making the urine alkaline is also effective in increasing urine salicylate excretion.
Forced alkaline diuresis is used if the blood level exceeds 500 mg litre-1 (3.6 mmol Iitre”) in adults, 300 mg litre”! (2.2 mmol litre “) in children. Increasing the pH of the urine from 7 to 8 increases the renal excretion of salicylic acid by about a factor of 10. In the first hour, 1500 ml of fluid should be given as 500 rnl 5% dextrose, 500 ml 1.4% sodium bicarbonate and then 500 ml 5% dextrose again. Sufficient potassium should be mixed with each 500 mI bag to keep the serum potassium level above 3.5 mmol litre “. If less than 200 rnl of urine is produced in the first hour, diuresis should be discontinued. The urine pH should be measured regularly every 15 or 30 min) and kept at between 7.5 and 8.5. The plasma pH and arterial blood gases should be monitored at least 2-hourly to ensure that pH does not rise above 7.6; the plasma electrolytes should also be measured. If facilities are not available for constant observation by medical and nursing staff, alkaline diuresis may be more dangerous than the salicylate poisoning itself and should not be used.
Self-poisoning with paracetamol is common and the outcome can often be fatal. Paracetamol is converted to a toxic metabolite, N-acetyl-p-benzoquinonimine, which is normally inactivated by conjugation with reduced glutathione. After a large overdose, glutathione is depleted and the toxic metabolite binds covalently with sulphydryl groups on liver cell membranes causing necrosis. Marked liver necrosis can occur with as little as 10 g (20 tablets), and death with 15 g. The prothrombin time (the The International Normalized Ratio, INR) is the best guide to the severity of the damage.
The clinical features in the first 24 hours include nausea and vomiting, but the patient is fully conscious. Most patients recover within 48 hours, but some develop liver failure, which usually becomes apparent in 72-96 hours. Acute renal failure can occur, sometimes in the absence of severe liver damage.
Treatment depends on the interval between overdose and presentation and on the plasma concentration of paracetamol. Blood for paracetamol level should be taken immediately.
Within 4 hours of ingestion, gastric lavage should be considered in adults who have taken a single dose of 7.5 g or more, and in children after a single dose of 150 mg kg-lor more. The antidote of choice is acetylcysteine given intravenously; it provides sulphydryl groups that increase the availability of hepatic glutathione. The decision to give treatment is based on the plasma paracetamol concentration, measured 4 hours after the overdose, or later by referring to a graph of log concentration against time, with a line joining 200 mg litre”! (1.32 mmol litre “) at 4 hours and 50 mg Iitre ” (0.33 rnmol litre “) at 12 hours (Fig. 14.5). If the concentration is above, on, or even slightly below, the line, treatment should be given. Care must be taken concerning the units in which the results of estimations are reported.
Some patients, including chronic alcoholics and those taking enzyme-inducing drugs such as phenytoin and carbamazepine, are at greater risk of liver damage and should be treated at concentrations of paracetamol half as great as those indicated by the standard treatment graph. For maximum protective action, treatment should be started within 8 hours. If a potentially toxic dose of paracetamol has been taken, treatment must be given at once. Therapy with acetylcysteine can be stopped if the concentration of paracetamol is subsequently found to be below the treatment line.
Acetylcysteine is given as an intravenous infusion diluted with 5% glucose solution with an initial dose of 150 mg kg’ in 200 rnl over 15 min followed by 50 mg kg:’ in 500 ml in 4 hours, and then 100 mg kg-l in 1 litre in the following 16 hours. Occasionally, patients develop a pseudoallergic reaction with wheezing, flushing and hypotension, and if this occurs the infusion should be suspended. Intravenous hydrocortisone and chlorpheniramine should be injected and the infusion restarted at a lower rate when the reaction has subsided.
Oral methionine is an alternative and is significantly cheaper than acetylcysteine but absorption and efficacy is unreliable if the patient is vomiting. The benefit of methionine in patients presenting late has not been determined. The dose is 2.5 g by mouth every 4 hours for a total of four doses.
Pregnant women should be treated in the same way as other patients and there is no evidence that either acetylcysteine or methionine are teratogenic or fetotoxic. Concentrations of paracetamol are not a reliable guide to the value of treatment in patients who present more than 16 hours after ingestion of the drug. The benefit of treatment with acetylcysteine after 24 hours has been established only in patients who have evidence of encephalopathy but it is worth treating all patients who have taken a potentially dangerous overdose (more than 150 mg kg:’) and who present 16-24 hours later. Treatment can be stopped 24 hours after ingestion if the patient is asymptomatic, if the plasma paracetamol level is below 10 mg litre’? and if the INR is normal. The risk of severe liver damage is assessed from measurement of the INR, serum creatinine concentration and blood pH. A poor prognosis is indicated by an INR above 3, raised serum creatinine concentration or a blood pH below 7.3 recorded more than 24 hours after overdose. If any of these abnormalities are present, advice should be sought from a specialist liver or poisons treatment unit.
In patients who present within 8 hours of the overdose, the INR and serum creatinine should be measured about 24 hours after the overdose or when treatment with the antidote is complete. Patients with normal values can be discharged. For patients presenting after 8 hours, the INR and serum creatinine should be measured after completion of treatment and at 48 hours after overdose. Patients should remain in hospital until it is clear that the tests are not dangerously abnormal and the values are returning towards normal.
If a combination of paracetamol and dextropropoxyphene has been ingested, naloxone should be given intravenously in an initial dose of 0.8-2 mg and repeated at 2-3 min intervals up to a total of 10 mg if necessary. If this combination is taken with alcohol, then death from respiratory depression may occur rapidly.
In patients who present after 16 hours it is important to monitor and maintain fluid and electrolyte balance and glucose levels and to monitor for signals of encephalopathy. Haemorrhage should be treated with fresh frozen plasma. Patients with incipient or established hepatic failure may be candidates for haemoperfusion or liver transplantation. Those who develop severe hepatic damage and then recover do not develop long-term sequelae and can be treated with normal therapeutic doses of paracetamol. Non-steroidal anti-inflammatory
Self-poisoning with NSAIDs has increased, particularly as ibuprofen is available without prescription. Overdoses will produce a variety of effects including nausea, vomiting, headache, tinnitus and gastrointestinal bleeding. Severe poisoning causes widespread metabolic abnormalities, hepatic and renal damage, and convulsions occur with mefenamic acid. Treatment is with gastric lavage leaving 50 g activated charcoal in the stomach, oral activated charcoal 50 g every 4 hours, intravenous cimetidine 200- 600 mg 6-hourly and diazepam for convulsions.
Opiates produce respiratory depression leading to coma. Pin-point pupils are seen. Naloxone 0.8-2 mg i.v. is a competitive antagonist but, as it is short -acting, repeated injections may be required.