Middle-aged men--a risk category regarding fatal poisoning due to dextropropoxyphene and alcohol in combination.

BACKGROUND: Dextropropoxyphene (DXP) toxicity is highly potentiated by alcohol and the aim of this study was to determine the characteristics of non-suicidal deceased with simultaneous occurrence of alcohol and DXP in the blood. METHODS: The investigated population was based on the total medico-legal autopsy material in Sweden during the years 1992-1996. Toxicological analyses and death certificates were examined. RESULTS: Simultaneous occurrence of DXP and alcohol was detected in 425 cases. The mean blood alcohol concentration was 0.14%. One-third had a blood alcohol concentration >;0.20% and 42%, <0.1%. The majority of the cases were found between the ages 30 and 59 years;, 71% were male and 29% were female. Notes on alcoholism were found in 16% of the cases. CONCLUSION: Middle-aged, habitual or social-drinking men, on medication for pain, are most prone to combine DXP and alcohol and are most vulnerable to be victims of accidental poisoning due to the combination of DXP and alcohol. We propose strict regulations in prescription, or even a ban on prescription of DXP, and that physicians in the meantime pay extra attention to this risk category of patients and make sure that the patient is well informed of the life-threatening risks of simultaneous use of DXP and alcohol.

The prevalence of analgesics containing dextropropoxyphene or codeine in individuals suspected of driving under the influence of drugs.

To investigate the prevalence of analgesics containing dextropropoxyphene (DXP) or codeine in individuals suspected of driving under the influence of drugs, we analysed all blood samples in which drugs were screened for in cases of suspected drunken driving in Sweden during the years 1992-1997. DXP was found in 130 (2.7%) and codeine in 388 (7.9%) of the 4896 drug-screened cases. The ratio between the number of DXP and of codeine cases and prescription of defined daily dose/1000 inhabitants during a 12-month period (DDD) was determined. The quotient for DXP was trebled from 1992 (0.99) to 1997 (2.89), while the codeine quotient decreased by 9% (from 6 to 5.5). The blood samples showed polydrug use in all but 28 cases of the 486 cases where DXP and/or codeine was found. In 71% of the 486 cases benzodiazepines were also present and in 38% of the cases amphetamine and/or cannabis were present. It was concluded that analgesics containing DXP or codeine are not drugs of primary interest in this specific population. Nevertheless, because of the high toxicity of DXP, especially when combined with alcohol or other drugs, the increase in the DXP prevalence gives reason for concern, since the studied population represents a group of individuals who use large doses of therapeutic or illegal drugs.

Among fatal poisonings dextropropoxyphene predominates in younger people, antidepressants in the middle aged and sedatives in the elderly.

To compare the characteristics of dextropropoxyphene (DXP) poisoning victims with those of victims of poisonings by antidepressants and sedatives, we examined all fatal poisonings due to DXP, antidepressants or sedatives among autopsies performed at one department of forensic medicine in Sweden during the six-year period from 1992 to 1997. In 202 cases, death was classified as fatal poisonings by DXP, antidepressants or sedatives. DXP caused death in 78 cases (39%), antidepressants in 49 (24%), and sedatives in 75 (37%). DXP as a single preparation was predominant in causing death. The second compound, flunitrazepam, caused death in 30 cases (15%). The victims of poisonings by DXP, antidepressants, or sedatives shared a similar history of alcohol/drug abuse, depression and somatic illness. They were mostly living alone at the time of death (>60%), the majority died at home (81%), and suicide was the most frequent manner of death (73%). Age seemed to be an important characteristic regarding the choice of drug. Younger people predominantly died of DXP (mean age 43 years, 95% confidence interval, CI 39-47), and elderly people of sedatives (mean age 59 years, CI 55-63). Antidepressants were found mainly in middle-aged victims (mean age 51 years, CI 48-54). The predominance of sedatives among the elderly might be explained by a very high prescription rate of such drugs in older age groups, but prescription rate could not explain the DXP predominance among younger people. We hypothesize that younger people are more prone to abuse therapeutic drugs for euphoric reasons than elderly people, and that because of its high toxicity, DXP leads to accidental deaths more often than sedatives.

Correlation between prescription of various dextropropoxyphene preparations and their involvement in fatal poisonings.

In Sweden, the frequency of fatal poisoning by dextropropoxyphene (DXP) ingestion is constantly high. There are seven preparations containing DXP on the Swedish market; in three of them DXP is the sole analgesic ingredient, while four of them are combinations of analgesics. In an attempt to assess the death rate attributable to each DXP preparation on the basis of toxicological analyses, altogether 834 cases of dextropropoxyphene-related death over a 5-year period (1992-1996) in Sweden have been reviewed. The ratio between number of fatal poisonings and prescription of defined daily dose/1000 inhabitants during a 12-month period (DDD) was determined. The highest ratio, 27, was attributed to unmixed preparations. The ratio for DXP + paracetamol-related deaths was 6.3, and for DXP + phenazone, 6.4, while the lowest ratio, 2, was found among the DXP + chlorzoxazone cases. The unmixed preparations, representing 26% of all DXP prescriptions during the study years, were implicated in 62% of the DXP fatalities, a considerable over-representation. Unmixed preparations, with their higher content of DXP, may be more attractive for many consumers because of their narcotic (euphoric) effects rather than for any analgetic superiority. Another possibility is that unmixed preparations may erroneously have been regarded as safer than when combined with paracetamol, as reports of poisoning with compounds containing DXP + paracetamol have been most frequently reported, probably due to their predominance on the market.

Fatal poisonings where ethylmorphine from antitussive medications contributed to death.

The hypothesis that antitussives containing ethylmorphine are abused by alcoholics and drug addicts and that this may lead to fatal poisonings where ethylmorphine causes or contributes to death was investigated. For this purpose 14 cases were analysed where a blood ethylmorphine concentration above the therapeutic level of >/= 0.3 microg/g was found in autopsy blood samples. Alcohol was found in 8 of the 14 cases and alcoholism or drug addiction was noted on 8 of the 14 death certificates. Other drugs, mostly benzodiazepines, were found in all 14 cases. The cause of death was fatal poisoning in 8 of the 14 cases and although there were no mono-intoxications, the cause of death was specified as fatal ethylmorphine poisoning in 2 cases. Among the unspecified medicinal drug poisonings there were five cases with very high blood levels of ethylmorphine, indicating that this drug played an important contribution to the cause of death. The results indicate that deaths due to ethylmorphine in antitussive medicines may occur among drug addicts and alcoholics taking it in overdose. Physicians should therefore be restrictive in prescribing cough mixtures containing ethylmorphine to these categories of patients. Prescription of large amounts of the drug should be avoided.

Suicides may be overreported and accidents underreported among fatalities due to dextropropoxyphene.

Among prescribed drugs in Sweden dextropropoxyphene (DXP) is the medical compound most frequently responsible for self-inflicted fatal poisonings. To analyze the process leading to the classification of the manner of death in cases of fatalities where DXP caused or contributed to death, a set of explicit and implicit operational criteria was applied retrospectively to fatal DXP poisonings among autopsy cases performed at one department of forensic medicine in Sweden during the six-year period from 1992 to 1997. DXP fatality was found in 113 (2.6%) of the total 4306 autopsy cases. Suicide was recorded in 84 (74%) of these cases, and an undetermined manner of death in 24 (21%). Explicit unambiguous expressions of the intent of the decedent were found in 29 (26%) of the 109 analyzed cases. (In four cases no analysis could be performed). In 46 cases only implicit and no explicit criteria were found. The total number of implicit criteria in individual cases without explicit criteria never exceeded three and in 34 cases no criteria of any type were documented. It is concluded that the classification of the manner of death at DXP fatalities was often based on very limited grounds when the operational criteria were used as a standard for comparison. Information from relatives, friends and others concerning the decedent was rarely accessible. The shortage of information probably led to deficiencies in the death statistics concerning DXP fatalities. Considerable underreporting of accidents and probable overreporting of suicides were found. Failure to report DXP deaths as accidents may delay discovery of the high toxicity of this drug. This might be one of the reasons why the DXP fatality rate is still constantly high in Sweden, while both Denmark and Norway have managed to decrease their DXP death rates by vast restrictions, based on alarming reports of accidental DXP fatalities. In order to guarantee valid death statistics concerning self-inflicted poisoning, the information base leading to classification of the manner of death has to be enlarged. This requires implementation of new routines, including interviews of relatives, acquaintances and significant others to get the information needed to assess the decedent's intention to die. Operational criteria may facilitate the difficult classification process by providing a structured standard, and the set of explicit and implicit criteria applied in this study is recommended.

The prevalence of dextropropoxyphene in autopsy blood samples.

The prevalence of dextroproxyphene (DXP) in the total medico-legal autopsy material in Sweden during 1992 to 1996 was examined. Simultaneous findings of paracetamol and alcohol in the blood were considered in the analyses. DXP in peripheral blood was found in 1782 (7.5%) of the 23,691 cases analysed during 1992-1996. The autopsy prevalence of DXP increased by 25% from 1992 to 1996. The mean blood DXP concentration was 1.62 micrograms/g (the blood level of DXP after a therapeutic dose is 0.05-0.75 microgram/g). The blood DXP level was < 0.75 microgram/g in 947 cases and > or = 0.75 microgram/g in 835 cases. The cases < 50 years of age had a significantly higher mean concentration (2.36 micrograms/g) than those > or = 50 years (1.04 micrograms/g). Paracetamol in the blood was found in 53% of the DXP cases (mean 75.0 micrograms/g; therapeutic level 2.5-25 micrograms/g) and alcohol in 43% (mean level 0.14%). According to the death certificates 54% (956) died from fatal poisoning. Among these, 74% (707) showed a blood DXP concentration > or = 0.75 microgram/g. Other Scandinavian countries, Denmark and Norway have reduced the rate of fatal DXP poisonings through government regulations for prescription. As the defined daily dose/1000 inhabitants during a 12-month period (DDD) of DXP preparations in Sweden (14.4 in 1996) is six times as high as in Denmark and nine times as high as in Norway, introduction of similar regulations in Sweden should be considered.

The manner of death among fatalities where dextropropoxyphene caused or contributed to death.

Dextropropoxyphene (DXP) is one of the most prescribed analgesic compounds in Sweden. To investigate the manner of death among fatalities where DXP caused or contributed to death all medico-legal autopsies performed in Sweden in 1992-1996 were analysed on the bases of toxicological analyses and death certificates. DXP in peripheral blood was found in 1782 (7.5%) of the total 23,691 blood samples. According to the death certificates 956 (54%) of the 1782 cases were classified as fatal DXP poisoning. Among these, the manner of death was classified as accidental in 49 cases (5%), suicidal in 542 cases (57%) and undetermined in 365 cases (38%). The reported manner of death differed between the six forensic medicine districts in Sweden. The accident rate differed significantly between the district with the highest rate (9%) and the districts with the lowest rate (1%). One district had a significantly higher incidence of suicide (73%) than four of the other districts, while another district had a significantly lower incidence of suicide (33%) than all the other districts. The accident classification rate among the physicians performing ten or more autopsies varied from 0% to 17%, the suicide classification rate from 25% to 83% and the rate of undetermined manner of death from 8% to 71%. A major conclusion drawn from this study is that accidental DXP fatalities may be underestimated. This may have serious consequences, as under-reporting of accidental DXP fatalities will increase the risk that knowledge of the high toxicity of DXP will not reach the population consuming this drug. Since valid death statistics concerning the manner of death at DXP fatalities are needed to provide the base for preventive actions, special attention should be paid to the classification process, in order to increase the uniformity of the assessments among the different physicians, and to avoid under-reporting of accidents.

Analgesic use disorders among orthopedic and chronic pain patients at a rehabilitation clinic.

Interviews were conducted with 265 orthopedic and chronic pain patients, using a structured diagnostic instrument (ADDIS/SUDDS) concerning their use of analgesics. Twenty-two percent of the patients met criteria for analgesic use disorders in accordance with DSM-III-R; 18.5% fulfilled DSM-IV criteria. Dextropropoxyphene was the most common analgesic prescribed and was used by 47% of the patients who met criteria for analgesic use disorders. It is concluded that patients with chronic pain using narcotic analgesics are at considerable risk of developing analgesic use disorders. Assessment of the use of analgesics should be offered to pain patients taking narcotic drugs.

The feasibility of a new intake routine to assess substance use disorders by means of a structured interview.

A structured interview, ADDIS (Alkohol Drog Diagnos InStrument), designed to assess substance use disorders, was included as a part of the intake protocol in a department of orthopedics at a general hospital. To evaluate both the effectiveness and feasibility of the new procedure, the attitudes of 29 staff members were sampled during follow-up interviews. In addition, a questionnaire was sent to 254 patients to examine their opinions about the interview. The staff made a global evaluation of the new routine on a 10-point scale, ranging from completely negative (1) to completely positive (10). The mean rating was 8.2 (range 5-10). The evaluations made by the staff members in the interviews were very positive. Of the 254 patients, 177 (70%) returned the questionnaire. More than 90% of the patients appreciated being asked about their use of analgesics and sedatives, and 77% felt it was positive to be asked about their alcohol use. The result of the patient questionnaire supports the feasibility of the routine, suggesting that a structured interview can be included in the intake protocol in order to improve the assessment of substance use disorders.