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Paracetamol and dextropropoxyphene were implicated on clinical and analytical grounds in 237 poison deaths in England and Wales in 1979. In addition to paracetamol, dextropropoxyphene and ethanol, other agents were detected in 61 of these cases (26%). Analytical evidence suggests that very substantial overdoses of paracetamol and dextropropoxyphene were ingested in the majority of cases; their mean plasma concentrations in those ingesting no other agents were 252 and 8.64 mg/l respectively. Significant quantities of ethanol were ingested in 133 of 237 cases (56%). The mean ethanol concentration in those in whom quantitative estimations of paracetamol, dextropropoxyphene and ethanol were undertaken and who had not ingested other drugs, was 1588 mg/l. There was no analytical support for the diagnosis of paracetamol and dextropropoxyphene poisoning in 74 of 305 cases (24%) of H.M. Coroners' returns to the Office of Population, Censuses and Surveys for the period 1 January-31 December 1979. In addition, dextropropoxyphene was detected analytically in six cases classified as being due to paracetamol alone.

Coroners' files have been examined to ascertain the numbers of deaths involving self-poisoning with analgesic drugs with specific reference to the paracetamol/dextropropoxyphene combination. The period of study was 1976-1980. This report concentrates on cases in England, although reference is made to similar deaths occurring in Scotland and Northern Ireland. Data have been collected extensively on a wide range of issues concerning fatal self-poisonings mainly by visiting coroners' offices in England to make direct investigation of records. The total number of cases where the paracetamol/dextropropoxyphene combination can be considered as ingested in the self-poisoning episode is underestimated. The number of cases involving alcohol and/or other drugs taken together with the combination product is particularly underestimated. Involvement of people aged 30 years and below comprises 32% of all cases. 'Gesture' overdoses comprise an estimated 14% of all cases in England. An analysis of fatalities from cases where quantities in post-mortem blood of dextropropoxyphene less than 1 microgram/ml and paracetamol less than 50 micrograms/ml are found and of cases where death occurs within 2 h of ingestion of the overdose has been carried out. The results are inconclusive. In most cases alcohol and/or other drugs are found to be involved. Critical inspection of coroners' files shows relatively few of these cases where the combination product is ingested on its own. There is wide variability in the data available in coroners' files. In many cases data of value to this research are not recorded. Medical history and quantitative levels of drugs suspected (particularly dextropropoxyphene) are particular examples of factors which may not be recorded. Office of Population, Censuses and Surveys (OPCS) mortality data are based on certified causes of death. Because of the underestimate of the involvement of this combination product and the under-reporting of other drug and/or alcohol ingestion with the combination, care must be exercised in quoting or drawing conclusions from OPCS statistics.

Dextropropoxyphene has been increasingly prescribed as an analgesic in the UK, chiefly in the form of Distalgesic (dextropropoxyphene hydrochloride 32.5 mg and paracetamol 325 mg per tablet). After reports of sudden deaths from the misuse of this combination, prescribing is declining. Distalgesic remains the most common cause of fatal drug overdose in the West Midlands, UK. The 1983 Birmingham inquests are compared with those from the year 1976 to 1979. In comparison with other drug fatalities, death characteristically occurs rapidly, as little as 1 h after ingestion and usually before hospital treatment can be initiated. Toxicity is increased by alcohol which is also extensively abused. The fatal dose may be as small as 15 tablets or possibly less. Many victims are young and some never intended to take their life. Convulsions and respiratory failure precede death. The elderly and respiratory cripples may be more vulnerable to accidental death. Evidence suggests a liability to dependence or even addiction with dextropropoxyphene.

Difficulties in the estimation and interpretation of dextropropoxyphene and norpropoxyphene analyses have added to the controversy concerning the toxicity of these compounds. Poor performance in external proficiency assessment trials reflects the unsatisfactory state of many dextropropoxyphene and norpropoxyphene analyses in general use. There is substantial overlap between blood concentrations of dextropropoxyphene and norpropoxyphene encountered in chronic therapeutic dose and those associated with acute toxicity. As dextropropoxyphene and norpropoxyphene are often taken in overdose with other drugs, their blood concentrations must be interpreted in the context of careful identification and quantitation of such agents. The present availability of accurate methods for measurement of parent drug and metabolite should now make anecdotal reports unsupported by analytical data entirely superfluous.

To determine reasons for the continuing mortality in patients taking a paracetamol overdose, the presentation, drug ingestion history, patient background, use of antidote (N-acetylcysteine and methionine), clinical course and outcome were determined in 247 patients treated at King's College Hospital in 1982 and 1983. Patients (147) were referred from other centres because of severe liver damage and 100 were local patients seen in the accident and emergency department. Survival in the local patients was 100% and, for those with severe liver damage, 49 and 63% (1982 and 1983 values). Delay in initial presentation to hospital was a major factor in determination of an adverse outcome, with a median delay of 30 h in the referred patients and 8 h in the local cases. Such a delay precluded administration of antidote to the majority of patients in the referred group, but in 11 cases where antidote could have been given a full course was not provided and all 11 patients died. Included among these were four patients in whom the serum paracetamol concentration was in the 'non-toxic' range. One patient with a chronic alcohol-drinking history (greater than 200 g/day) received N-acetylcysteine at 12 h but died from liver failure. However, in the complete series prior alcohol consumption was not associated with a significantly worse prognosis and simultaneous ingestion of alcohol with paracetamol had no effect on outcome. The concomitant ingestion of dextropropoxyphene caused an early and marked impairment of consciousness unrelated to any hepatotoxicity but, in three cases where dextropropoxyphene combinations were used, death occurred subsequently from liver failure.

This survey continues and expands earlier studies (Finkle et al., 1976a, b). A total of 27 medical examiner or coroner offices across the USA and Canada were visited. The combined jurisdictional population of these 27 sites is 64.8 million people: 56.5 million people in the USA (27% of the US population) and 8.3 million in Canada (Ontario). Since 1969 through mid-1983, a total of 4412 cases provided information sufficient for inclusion in this study. In each of the cases the presence of propoxyphene, and often its major metabolite, in the blood or tissues of the deceased was confirmed by toxicological analysis at the survey site. The following is a summary of the survey findings: The incidence of propoxyphene-associated deaths reached a peak in 1977, then declined by 22.2% from 1977 to 1978 and by 33.3% from 1978 to 1979, and by a further 10-18% since then. This continuing decline has occurred despite increased interest in propoxyphene misuse and the existence of improved analytical methods for the detection of propoxyphene and its metabolites. The decline is greater than can be accounted for by the decline in propoxyphene prescribing. The most common manner of death was suicide, accounting for about 45% of the cases; it can be safely assumed that the suicides were under-reported. A large majority of the suicides involving propoxyphene were multiple-drug intoxications, including alcohol. Propoxyphene alone was noted in about one-sixth of the suicides. These findings confirm those of the earlier studies, i.e., that a high proportion of the deaths associated with propoxyphene are suicides, and, in most cases, the deceased were victims of multiple-drug toxicity. More than 90% of cases involved persons between the ages of 20 and 40 years. There were very few instances of paediatric, adolescent or older adult deaths associated with propoxyphene. There is no evidence to support the view that the deceased were part of the street drug-abuse population. A history of heroin abuse appeared in less than 5% of the cases. Even fewer people had been known to have abused propoxyphene before their deaths, but 18% of the population had been known to 'self-medicate', using multiple drugs without appropriate medical supervision. The distribution of males to females approximated that of the US population.(ABSTRACT TRUNCATED AT 400 WORDS)

The sale of dextropropoxyphene is rising in Denmark, and the number of both fatal and non-fatal cases of poisoning with dextropropoxyphene is similarly rising. A total of 124 fatal and 297 non-fatal hospitalized cases of poisoning caused by dextropropoxyphene were reported to the National Board of Health in 1984. These figures are judged to be minimum figures. There is an accumulation of cases in the municipality of Copenhagen as compared to the remainder of the country. Cases of poisoning with dextropropoxyphene occur more frequently in socially and mentally encumbered groups. It is often difficult to determine with certainty the method of poisoning, but it is considered that the distribution is roughly one-third suicide or attempted suicide, about the same from accidental or simple over-dosage, while the remainder are uncertain. It is judged that the number of suicides or attempted suicides in normal persons is small, while the numbers in persons not entirely normal or carried out as an impulsive act are considerably higher. Other intoxicants, most frequently alcohol, have in more than one half of the cases been consumed together with dextropropoxyphene. The mortality rate for those cases reaching medical aid has been found to be 3.6% which is lower than the figure reported in other investigations. Very many of the cases of poisoning, however, are fatal at the time of discovery. Serious sequelae after non-fatal cases of poisoning are extremely rare. The steps being taken by the National Board of Health to reduce the number of cases of poisoning are mentioned, and the possibilities of reducing the number of cases are also discussed.