The use of analgesics in patients with asthma.

Aspirin (acetylsalicylic acid) and other nonsteroidal anti-inflammatory drugs (NSAIDs) cause deterioration in respiratory function in approximately 10% of adults with asthma and a smaller proportion of children with asthma. We propose evidence-based guidelines for the safe use of NSAIDs in individuals with asthma following systematic review of data from the last 10 years relevant to the use of these drugs in such patients. We would currently recommend that patients with asthma who are known to be intolerant of NSAIDs or who exhibit any of the high risk clinical features for intolerance to these drugs (severe asthma, nasal polyps or chronic rhinosinusitis) should use NSAIDs only under close medical supervision. In those with high risk features formal aspirin provocation testing would be recommended prior to the therapeutic use of NSAIDs. Those individuals with asthma who regularly use NSAIDs can continue to do so but should be warned that intolerance to NSAIDs can develop late in life. Lack of relevant experimental evidence precludes the production of evidence-based guidelines for the group of patients with asthma who do not exhibit high risk clinical features and who have never before used NSAIDs. We would currently recommend that this group be treated as potentially intolerant to NSAIDs and use of these drugs can only be recommended under medical supervision but note that further studies and clinical experience could be expected to relax this restriction for many patients. Recent data have suggested that frequent use of paracetamol (acetaminophen) may contribute to a deterioration of respiratory function in asthma. A small proportion of patients with asthma who are NSAID-intolerant experience short-lived deterioration in respiratory function with the use of high doses of paracetamol but this is uncommon and has not been implicated in life-threatening reactions. Routine warnings about paracetamol use in asthma are, therefore, not warranted. Medical personnel, however, should be aware of the potential for worsening of symptoms in some individuals with asthma using paracetamol and institute formal investigation or withdrawal of the drug if they suspect such a reaction.

Apparent poisoning by wood preservatives: an attributional syndrome.

Recent reports have pointed to an increased number of patients presenting with multisystem symptoms which they attribute to chemical exposures or to heightened chemical sensitivity. Twenty patients exposed to wood preservative products, who attended a joint toxicology and psychiatric clinic, were reviewed by a retrospective case note analysis. Thirteen patients attributed their symptoms to the wood preservative soon after the exposure, and seven patients developed the attribution only at a later date. Reported symptoms referred to all body systems, but there were few physical signs. Clinical findings suggest that the acute symptoms were consistent with the expected toxic effects, but the chronic symptoms could not be explained physically. Patient's beliefs about chemical poisoning could be understood as arising in the context of an attributional process, representing a sociopsychosomatic syndrome precipitated by wood preservative exposure. Patient management included a discussion of findings from assessments, published information, along with counseling where appropriate. Follow-up information from their general practitioners indicated a possible improvement in 50% of patients.

Paracetamol overdose in pregnancy analysis of the outcomes of 300 cases referred to the Teratology Information Service.

A prospective study was carried out to investigate the outcome of pregnancy in 300 women who had self-administered an overdose of paracetamol, either alone, or as part of a combined preparation. Exposure occurred in all trimesters. The most striking feature of this study is that the majority of the pregnancies had normal outcomes. Over half of the mothers (160 = 53%) required treatment for the overdose, and 49 of these had specific antidotes (33 mothers had acetylcysteine and 16 mothers had methionine). The rest of the mothers were given nonspecific treatments including ipecacuanha (52), gastric lavage (42), and charcoal (16). None of the mothers died. There were 219 liveborn infants with no malformations, 61 of whom had been exposed in the first trimester. Eleven liveborn infants had malformations; none was exposed in the first trimester. On other infant exposed at 18 weeks had a diaphragmatic hernia; this pregnancy was terminated at 22 weeks. In none of these 12 infants can the malformations be directly associated with paracetamol exposure. There were no apparent differences either in the sex ratio or the body weights of term infants. There were seven full-term infants with neonatal problems that seem unrelated to paracetamol exposure. Six premature infants also had neonatal problems, which were more likely to be related to their degree of prematurity rather than paracetamol exposure. There was no obvious relationship between the time of exposure and the time of delivery. The overall conclusion is that paracetamol overdose per se is not an indication for termination of pregnancy.

Features, prevention and management of acute overdose due to antidiabetic drugs.

Hypoglycaemic medication forms a disparate group of therapeutic compounds including insulin, the sulphonylureas and biguanides. They are all designed to prevent hyperglycaemia and in general are well tolerated. Careful prescribing practice and patient education by the physician can do much to reduce the risk of adverse effects from diabetic therapy. However, the presentation of adverse effects, together with accidental and non-accidental overdose, is a frequent clinical problem. Furthermore, the possible impairment of hypoglycaemic awareness in patients prescribed human insulin has added complexity to diabetic management. The cardinal features of insulin overdose are hypoglycaemia and hypokalaemia. The sulphonylureas predominantly cause hypoglycaemia, while the biguanides may precipitate lactataemia and acidosis. Recognition of hypoglycaemia is therefore crucial in avoidance of toxicity. Intravenous dextrose is the mainstay of therapy following gut decontamination (for the oral agents). The efficacy of glucagon is dependent on hepatic glycogen stores and should therefore be used with caution. Diazoxide is not recommended. More recently, octreotide has been shown to be effective in sulphonylurea overdose. Patients should be admitted and monitored with serial blood sugar measurements for a minimum of 1 to 2 days as clinically warranted.

A study of self poisoning with oral salbutamol--laboratory and clinical features.

1. The recent increase in asthma mortality coupled with reports of fatal asthma associated with beta-2-agonist therapy, has stimulated interest in the plasma concentrations of beta-2-agonists that produce systemic toxicity. 2. We prospectively studied 17 patients (9 male), mean age 23 years (range 2-72), who attended the emergency departments of hospitals throughout the United Kingdom having recently ingested an overdose of salbutamol. 3. Clinical, laboratory, ECG data, plasma and urine samples were obtained from each patient. Plasma was assayed for salbutamol concentration using a high performance TLC-photodensitometric method. 4. The mean (+/- s.d.) salbutamol dose reported to have been ingested was 89(+83)mg and the mean plasma salbutamol concentration was 166 (range 18-449) ng ml-1. The mean plasma potassium was 2.9 (s.d. +/- 0.6) mM (n = 16). None of the patients in this study developed serious cardiac dysrrhythmias. 5. There were significant correlations between the plasma salbutamol concentration and plasma potassium concentration (r = -0.85; P < 0.00005) and between plasma salbutamol concentration and pulse rate (r = 0.66; P < 0.005). 6. We conclude that in these patients, without respiratory decompensation, suprapharmacological plasma concentrations of salbutamol were tolerated without serious cardiac arrhythmias or any fatalities.

Predicting severity of tricyclic antidepressant overdose.

The measurement of plasma concentration, a prolonged QRS interval, and level of consciousness have all been recommended as useful indicators of toxicity following tricyclic antidepressant overdose. The aims of this study were firstly, to determine the relative prognostic value of each of these indicators and secondly, to assess when a patient can be discharged safely from the intensive care unit. Data were evaluated on 67 patients with tricyclic antidepressant overdose from four centers. Plasma tricyclic antidepressant concentrations were measured, coma grade was evaluated using the Matthew-Lawson Coma Scale and a ECG was obtained from 23 patients on admission. Complications such as convulsions, hypotension, arrhythmias, and need for intubation and ventilation were recorded. Thirty patients developed complications and no patient died. Coma grade was the best predictor of outcome. The development of serious complications is unlikely in patients whose level of consciousness is grade II or less and who are admitted to hospital more than 6 h after overdose. Plasma tricyclic antidepressant concentration was of no additional value in predicting toxic complications or deciding when the patient could leave the intensive care unit. Our study suggests that an alert and orientated patient with a QRS duration less than 100 ms is the best indicator for safe transfer to a medical or psychiatric ward.