G.N. Volans

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.

Pharmacokinetics and Toxic Effects of Diltiazem in Massive Overdose

A 50-year-old man with ischaemic heart disease took 98 tablets of diltiazem 60 mg with alcohol. He developed a junctional bradycardia, hypotension and reduced cardiac function refractory to intravenous calcium gluconate. He survived with temporary cardiac pacing and infusion of dopamine. As much as half the dose was vomited back, but nonetheless the plasma diltiazem concentration reached 6090 μg/l before falling mono-exponentially with a half-life of 8.6 h. Sinus rhythm returned when the plasma concentration of diltiazem was around 750 μg/l. Standard resuscitative procedures sufficed to treat massive diltiazem overdosage.

Ibuprofen Overdose: The First Two Years of Over-the-Counter Sales:

Experience during 14 years of prescription only use indicates that the non-steroidal anti-inflammatory drug (NSAID) ibuprofen is of low toxicity in acute overdose. In August 1983 ibuprofen was licensed for over-the-counter (OTC) use in the UK and it was recognised that this change could have an impact upon the epidemiology of analgesic overdose in this country. The London centre of the National Poisons Information Service (NPIS) began a new prospective survey of ibuprofen overdose at the time of OTC release. The first 2 years of this survey detected a marked increase in enquiries concerning ibuprofen overdose but there was no evidence to contradict the former claims of low toxicity. The importance of continued monitoring is stressed.

Haemoperfusion: a useful therapy for a severely poisoned patient?

Although it is many years since a haemodialysis and haemoperfusion over uncoated and later coated charcoal columns have been used for the treatment of intoxicated patients, the clinical efficacy of these extracorporeal techniques in the treatment of severely poisoned patients remains a matter of debate. Some of the reasons for this controversy may be the indiscriminate use of haemoperfusion in any form of intoxication, the lack of well-controlled studies and the wrong interpretation of the high haemoperfusion clearance values sometimes obtained. Simple pharmacokinetic principles are applied to this type of treatment and some practical guidelines as to how and when haemoperfusion should be applied or presented are reviewed. The limited place of haemoperfusion in the treatment of severe poisoning, its further declining use in the future, at least in its present design, and some promising new treatments are emphasized.

Activated Charcoal in Tricyclic Antidepressant Poisoning

Tricyclic antidepressants (TCA) bind to activated charcoal both in vitro and in vivo in healthy volunteers after a therapeutic dose of TCA. These findings provide a basis for the routine use of activated charcoal in TCA poisoning. The object of this study was to examine the effect of a single dose of 20 g of activated charcoal in overdose patients. Ninety-one patients from four centres with suspected TCA overdose were entered into a randomized study. Gastric lavage was performed on all patients. Thirty-four received 20 g of activated charcoal and 43 served as controls. Fourteen patients were excluded. Plasma drug concentrations were taken on admission and at 1, 2, 4, 8 and 24 h. The incidence of toxic symptoms was registered during 24 h. There was no significant difference in the area under the plasma drug concentration versus time curve, the peak plasma concentrations or plasma half-lives between the two groups. Toxic symptoms were more frequent in the non-treated groups although this difference was not statistically significant. In patients with TCA overdose initially treated with gastric lavage, a single dose of 20 g of activated charcoal had no effect on the systemic absorption or elimination of TCA.

The Relationship between Plasma Ibuprofen Concentrations and Toxicity in Acute Ibuprofen Overdose

1 The information available from the literature and from a prospective survey of ibuprofen overdose being undertaken by the London centre of the National Poisons Information Service (NPIS) was examined utilizing the Generalized Linear Interactive Modelling (GLIM) statistical computing package. 2 This confirmed that timed ibuprofen plasma concentrations were related to the symptoms of tachycardia, dizziness, tinnitus, ocular symptoms and coma/stupor as well as to reversible renal impairment and plasma hepatic enzyme elevation. 3 The best model of the relationship between symptomatic toxicity and timed ibuprofen plasma concentrations, was an exponential equation in time. Because of the lack of specificity or sensitivity in this model, and absence of demonstrable clinical advantages from its application, we do not recommend its use as a guide to predict toxicity. 4 However analysis of a larger information base utilizing similar methodology could, by increasing the statistical power of the resultant model, provide a useful means of predicting ibuprofen toxicity. 5 A previously postulated relationship between post-ingestion ibuprofen plasma concentrations and toxicity was not confirmed.

A Study of Self Poisoning with Oral Salbutamol - Laboratory and Clinical Features

1 The recent increase in asthma mortality coupledwith 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 attendedthe emergency departments of hospitalsthroughout the United Kingdom having recently ingested an overdose of salbutamol. 3 Clinical, laboratory, ECG data, plasma and urine samples were obtained from each patient. Plasmawas assayed for salbutamol concentration using ahigh 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 potassium was 2.9 (s.d.±0.6) mM (n=16). None of-1. The mean plasma 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 ofsalbutamol were tolerated without serious cardiac arrhythmias or any fatalities.

Hazards of Household Cleaning Products

1 All enquiries received by the London Centre of the National Poisons Information Service [NPIS(L)] relating to household cleaning products were followed up by questionnaire for a 4-month period from November 1978 to February 1979. 2 130 reports (43% of total followed-up) were received. 3 The incidence of misuse of household cleaning products has remained largely unchanged since a less detailed survey was performed in 1974-1975. 4 The source of enquiries, age groups and products involved were similar to the earlier survey. 5 Sixty-two per cent of cases were asymptomatic and no serious or life-threatening reactions were reported. 6 Although an increasing number of patients were admitted to hospital, little treatment was needed and the use of gastric lavage and aspiration had declined markedly. 7 Household cleaning products in the UK still cause no serious poisoning when misused or accidentally ingested.

Toxicity Data Derived from Man

Whilst man may be ‘the ultimate experimental animal’, there are very definite ethical limitations on the experiments to which he can be subjected (1). There is thus a need to consider the human toxicity data derived in real life from various surveillance schemes, as well as any advances in the study of human volunteers.

Ibuprofen overdose — the first year following over-the-counter release

The National Poisons Information Service (NPIS) has been monitoring overdose with NSAIDs since 1980. On the basis of the results to date it has been reported that most of these drugs appear safer in overdose than do aspirin or paracetamol1. Ibuprofen, however, is the only member of the group where sufficient data have been collected to substantiate this claim.