Glyn N. Volans

The Epidemiology and Prevention of Paraquat Poisoning

1 In the UK there was an increase in the annual number of deaths associated with paraquat poisoning between 1966 and 1975. Since that time there has been little change in numbers. 2 High mortality is associated commonly with suicidal intent. Serious accidental poisoning from paraquat has never been frequent in the UK and there have been no deaths reported in children since 1977. 3 The National Poisons Information Service has monitored in detail all reports of paraquat poisoning since 1980. Of the 1074 cases recorded there were 209 deaths. In recent years serious poisoning has been more commonly associated with ingestion of concentrated products by males. Local exposure to paraquat has not resulted in systemic poisoning. 4 International data for paraquat poisoning is incomplete and difficult to compare. There is a scarcity of morbidity data at both international and national levels. Information obtained from Poison Control Centres indicates that paraquat poisoning occurs in many countries but detailed comparisons are hindered by lack of standardised methods of recording. 5 Various measures to prevent paraquat poisoning have been introduced. Their effectiveness has not been studied in detail. Some support is provided by the low incidence of serious accidental paraquat poisoning in the UK, but because of the suicidal nature of paraquat poisoning it is unlikely that current preventative measures will influence the number of deaths occurring each year. 6 Preventative measures against paraquat poisoning should be tailored to national needs, based on and assessed by epidemiological studies.

Accidental poisoning in childhood: a multicentre survey. 1. General epidemiology

1 As background to a study of the effectiveness of packaging in preventing childhood poisoning, the National Poisons Information Service coordinated a prospective survey, in which 9 Accident and Emergency (A & E) departments and 5 paediatric departments, between July 1982 and February 1984, recorded 2043 cases of suspected accidental poisoning in children aged 0-60 months. 2 The products implicated were drugs (59%), household products (37%) and plants (3%). The drugs most frequently implicated were analgesics, anxiolytics, cough medicines, oral contraceptives and drugs to supplement diet or treat dietary disorders. The most frequently implicated household products were cleaners such as bleach, detergent and disinfectant, and petroleum distillate. 3 Seventy-five per cent of the children were 2 and 3-year-olds. Fifty-six per cent were male. 4 Only 22% of the children had signs or symptoms on admission. In only 2 cases were these serious. Treatment other than ipecacuanha and/or oral fluids was seldom required. Of the cases where outcome was recorded, 56% were discharged from A & E. The rest were admitted to a ward; only 7 children were admitted to intensive care units. No child died. 5 Comparison with HASS and other epidemiological surveys shows that these results are representative of national trends.

Accidental poisoning in childhood: a multicentre survey. 2. The role of packaging in accidents involving medications

1 To assess the effectiveness of child-resistant closures (CRCs) and unit dose packaging in preventing childhood poisoning with medications, a survey by 14 hospitals of accidental suspected poisoning in children under 5-years-old, was compared with a survey of a representative sample of households with children under 5 living in the catchment areas of the hospitals. 2 Nine hundred and thirty-eight medications thought to have been ingested by 877 children were compared with 5827 medications found in households with children. The relationship between availability of packs or medications in the home and their involvement in accidents was quantified by means of an Accident Association Index (AAI). A low AAI indicated that the involvement of a pack or medication was less than expected from availability and therefore safe. A high AAI indicated that involvement was greater than expected and therefore unsafe. 3 Medications involved in suspected poisoning were most frequently packed in containers without CRCs (63%) or transparent blisters (20%); both had high AAIs. CRCs, strips, sachets and opaque blisters had low AAIs. 4 Analgesics, expectorants and gastrointestinal medications, had low AAIs, while oral contraceptives, hypnotics, sedative/tranquillizers, antidepressants, anticonvulsants, anti-emetics, and anti-infectives had high AAIs. Prescription medications were more frequently involved in accidents than over-the-counter (OTC) medications and had a higher AAI. 5 Comparison of the AAIs of different kinds of medication in each of their various pack types showed that safe packaging reduced the risk from medications which had a high average AAI. 6 Only 40% of medications were in their normal storage place at the time of the accident. Medicine and bathroom cabinets, and kitchen cupboards and drawers were the safest places to store medications. Handbags, fridges, and shelves or ledges in the bathroom were the most unsafe places. No pack had a low AAI when stored on open shelves indicating that safe packaging cannot compensate for unsafe storage. 7 Other factors which influenced the involvement of medications in accidents were the intended user and the duration of storage. 8 The results of the study have important implications for design of packaging for medications and for education of the public.

Acute Poisoning with Ibuprofen

1 Seventy five cases of ibuprofen overdose were recorded during a two year survey. 2 Details of the symptoms, treatment and the eventual outcome are known for 64% of the cases. The majority of the patients had no symptoms or only mild symptoms such as nausea or vomiting. 3 In the three cases where more serious symptoms were reported, the role of ibuprofen was not certain. 4 Laboratory analyses available for 13 cases demonstrated that plasma ibuprofen concentrations of up to 704 mg/l could be associated with no symptoms. 5 The data suggest that ibuprofen is of low toxicity in acute overdose and that therapy used should be supportive only.

Paracetamol Poisoning in Pregnancy: An Analysis of the Outcomes of Cases Referred to the Teratology Information Service of the National Poisons Information Service

A study was carried out to investigate the outcome of pregnancy in 115 women who had been exposed to paracetamol overdose. Follow up was obtained in 48 cases. Exposure occurred in all trimesters, and the most striking feature of this series is that the majority of the pregnancy outcomes were normal. None of the mothers died. There were 39 live born infants with no malformation, 14 of whom had been exposed in the first trimester. Four babies, exposed in the third trimester had neonatal problems, but these seem unrelated to paracetamol. There were two live born infants with gross malformations (spina bifida occulta; and cleft lip and palate). However, as the overdoses occurred at weeks 26 and 28 respectively, long after the structural development of these organs, the malformations could not have been caused by the paracetamol. There were two spontaneous abortions, both in the first trimester, which occurred two weeks after the overdose which may be related to the paracetamol. The overall conclusion is that paracetamol overdose per se is not necessarily an indication for termination of pregnancy.

Self poisoning in diabetic patients.

Recent reports suggest that self-poisoning with insulin in diabetics is more common than previously appreciated (Gale, 1980) whilst little is known of the extent of self-poisoning with other drugs in diabetics. We therefore made a prospective study of the pattern and the complications of deliberate self-poisoning in diabetic patients referrred to the National Poisons Information Service, London (NPIS) during the two years 1978 -1979. For comparison we have also reviewed a small series of reports of drug overdosage with antidiabetic drugs in non-diabetic patients.

An Investigation of the Role of the Specific Opioid Antagonist Naloxone in Clinical Toxicology

1 An assessment of the current role of naloxone in clinical toxicology has been made in a series of three separate epidemiological studies. 2 Through the National Poisons Information Service we found that the role of naloxone in opioid poisoning is often not appreciated by the enquirer and that toxicological screening is often requested before the diagnostic use of naloxone. 3 The recommended dose of naloxone (0.4-1.2 mg i.v.) is not always adequate. In 51 cases where naloxone was effective, doses of up to 3.2 mg were necessary (mean 1.8 ± 0.3 mg SEM i.v.). 4 In 31 cases of non-opioid poisoning, naloxone in doses of 0.4-1.2 mg i.v. caused no deterioration, whilst six patients in whom no opioids were detected showed clinical improvement. 5 In 300 cases of suspected ethanol-induced coma, 49 showed reversal of coma with naloxone, and in 38 cases ethanol was the sole cause of coma (mean plasma concentration 3.54 ± 0.62 g/l SEM). 6 These results suggest that the role of naloxone in clinical toxicology is not fully appreciated. There is a need for further education as to its indications in opioid poisoning, together with additional studies to define more accurately the dose/response relationship. In addition, the role of naloxone in coma induced by ethanol and certain other non-opioids needs to be evaluated further.

Features, Prevention and Management of Acute Overdose Due to Antidiabetic Drugs

SummaryHypoglycaemic 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.

Digoxin and Cimetidine: Investigation of the Potential for a Drug Interaction

1 The potential for a pharmacokinetic interaction between digoxin and cimetidine was investigated in a series of studies. 2 In a single-dose cross-over study in healthy volunteer subjects cimetidine increased the area under the plasma digoxin concentration curve and the peak plasma digoxin concentration. 3 In a repeated-dose study in healthy volunteer subjects taking digoxin 0.25 mg daily, co-administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.15 ng/ml. 4 In a repeated-dose study in healthy volunteer subjects taking digoxin 0.5 mg daily, co-administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.19 ng/ml. 5 In a repeated-dose study in patients receiving long-term digoxin therapy for atrial fibrillation co-administration of cimetidine had no significant effect on plasma digoxin concentrations. 6 We have shown that co-administration of cimetidine and digoxin in volunteer subjects causes a statistically significant but small increase in plasma digoxin concentration but no such increase was found in patients. We conclude that it is doubtful that this interaction is of any clinical significance.

A Survey of Non-Barbiturate Anticonvulsant Drug Overdose Reported to the Poisons Information Service (UK)

Self-poisoning is thought to be a significant complication of epilepsy (Mackay, 1979). Of the commonly prescribed anticonvulsants only phenobarbitone is well documented in overdose. In 1979 the National Poisons Information Service (NIPS) began a three year prospective survey of non-barbiturate anticonvulsant overdoses reported to the service to study the incidence and severity of poisoning with these drugs. Case histories were obtained for 150 cases, 123 adults and 27 children. The most frequently ingested drugs were carbamazepine 48 %, phenytoin 33 % and sodium valproate 16%. Overdoses of other anticonvulsant drugs were also