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P Holmgren

Publications and source records attributed to P Holmgren.

At least 19 recordsLinked to original sources

Fatal poisoning in Nordic drug addicts in 2002.

The present study from 2002 includes medicolegally examined fatal poisonings among drug addicts in the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. A common definition "drug addict" is applied by the participating countries. The number of deaths, age, sex, place of death, main intoxicant and other drugs present in the blood are recorded in order to obtain national data, as well as comparable Nordic data and data comparable to earlier studies from 1997 and 1991. The Icelandic results are commented on separately due to the low number of cases. The most fatal overdoses are seen in Norway, in both the death rate (number per 100,000 inhabitants=8.44) and in absolute number (n=232). The comparable figures for the other four countries are Denmark 5.43 (n=175), Iceland 3.6 (n=6), Finland 2.93 (n=94) and Sweden 2.56 (n=136). In earlier studies from 1991 and 1997, the highest death rate is seen in Denmark, with Norway as number two. Denmark is the only country where the death rate decreases from 1997 to 2002. A relatively large increase in deaths in the younger age groups (<30 years) is noted from 1997 to 2002, except in Denmark, where only a small increase in overdose deaths in very young people (15-19 years) is observed. Females account for 12-20% of the overdoses (three out of six deaths in Iceland). Relatively fewer deaths are recorded in the capital areas in 2002 than in 1997 and 1991, suggesting more geographically widespread drug use in the Nordic countries. Heroin/morphine is the single most frequently encountered main intoxicant, varying from 10% of the cases in Finland to 72% of the cases in Norway. Finland differs from the other countries in that a high percentage of the fatal overdoses in Finland are not caused by an illicit drug; buprenorphine overdoses are seen, and relatively few deaths resulting from heroin are seen. Methadone is the main intoxicant in 41% of the Danish overdose cases, 15% of the Norwegian cases, 4% of the Swedish cases and none of the Finnish overdose cases, an observation probably linked to different national prescription rules for methadone. The analytical screening reveals extended polydrug use. Frequently seen substances, in addition to the main intoxicant are amphetamine, tetrahydrocannabinol (THC), benzodiazepines and ethanol.

Adolescent↗

Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: a controlled forensic database study of 14,857 suicides.

OBJECTIVE: To test the hypothesis that selective serotonin reuptake inhibitor (SSRI) antidepressants may have a suicide emergent effect, particularly in children and adolescents. METHOD: Detections of different antidepressants in the forensic toxicological screening of 14 857 suicides were compared with those in 26,422 cases of deaths by accident or natural causes in Sweden 1992-2000. RESULTS: There were 3411 detections of antidepressants in the suicides and 1538 in the controls. SSRIs had lower odds ratios than the other antidepressants. In the 52 suicides under 15 years, no SSRIs were detected. In 15-19-year age group, SSRIs had lower relative risk in suicides compared with non-SSRIs. CONCLUSION: The hypothesis that treatment of depressed individuals with SSRIs leads to an increased risk of suicide was not supported by this analysis of the total suicidal outcome of the nationwide use of SSRIs in Sweden over a period of 9 years, either in adults or in children or adolescents.

Adolescent↗

High concentrations of diazepam and nordiazepam in blood of impaired drivers: association with age, gender and spectrum of other drugs present.

A zero-concentration limit for controlled scheduled drugs in the blood of motorists was introduced in Sweden in 1999 and the annual number of arrests for driving under the influence of drugs (DUID) has since increased eight-fold. However, for prescription drugs that might cause impairment (e.g. benzodiazepines) additional proof is needed to justify prosecution, such as whether the medication was being misused. Over a 2-year period, we found 94 cases of DUID in which the concentrations of diazepam in blood was 1.1 microg/g or more. Diazepam (D) and nordiazepam (ND) were determined in whole blood by capillary gas chromatography with a limit of quantitation of 0.05 microg/g for each compound. The mean (median) and maximum concentrations of D were 2.0 microg/g (1.7 microg/g) and 7.8 microg/g and the corresponding ND concentrations were 1.5 microg/g (1.0 microg/g) and 7.6 microg/g, respectively. The concentration of D in blood exceeded 2 microg/g in 21% of cases and was over 3.0 microg/g in 11% of cases. D and ND were the only drugs present in eight cases (seven men and one women) and in another five cases ethanol was present at concentrations ranging from 0.81 to 1.98 mg/g. Polydrug use was very common in these DUID suspects and D and ND coexisted with amphetamine in 20% of cases, tetrahydrocannabinol in 18% of cases and with both these illicit drugs in 12% of cases. The next most prevalent drug combination was D, ND and morphine (mostly derived from heroin), seen in 13% of cases. Other psychoactive prescription drugs were identified in blood including alprazolam, flunitrazepam, oxazepam, zolpidem and zopiclone. This case series of DUID suspects demonstrate the high frequency of polydrug use showing preference for illicit drugs like amphetamine, cannabis and heroin, in that order. Furthermore, Swedish traffic delinquents frequently overdose with prescription drugs as exemplified here by unusually high concentrations of D and its active metabolite ND.

Adolescent↗

Fatal intoxication cases: cytochrome P450 2D6 and 2C19 genotype distributions.

OBJECTIVE: Many commonly used pharmaceuticals, such as antidepressants and neuroleptics as well as some illegal drugs, are metabolised by the cytochrome P450 enzyme debrisoquine 4-hydroxylase (CYP2D6). Of Caucasians, 7-10% lack this enzyme, which can, upon administration of drugs in normal therapeutic doses, lead to adverse reactions and unexpected intoxication, leading in turn even to a fatal outcome in some cases. METHODS: Individuals (n=242) who had died due to intoxication by pharmaceuticals were genotyped for CYP2D6 and CYP2C19 and compared with a reference group of 281 blood donors. A single nucleotide polymorphism (SNP) method was used to identify five CYP2D6 alleles: *1 (wt), *2, *3, *4 and *6. The allele *5, a complete gene deletion, was identified by a multiplex amplification of long DNA fragments. Four CYP2C19 alleles *1 (wt), *2, *3 and *4 were also identified by SNP analysis. RESULTS: The prevalence of the CYP2D6 poor metaboliser (PM) genotypes in individuals with fatal intoxication was lower (4.7%) than expected from the frequencies of these genotypes in the blood donors (8.5%). A significantly lower frequency P<0.005 (0.03 with correction according to Bonferroni) was found for the CYP2D6*4 allele among the fatal intoxication cases. The CYP2C19 genotype analyses showed the same results for the fatal intoxication cases and for the blood donors. CONCLUSIONS: The findings in this study confirm our earlier observations of a lower frequency of CYP2D6 PM genotypes in cases of fatal intoxication. To our knowledge, it has not been shown previously that intoxication victims might have a lower frequency of PMs than the general population.

Aryl Hydrocarbon Hydroxylases↗

Urine/blood ratios of ethanol in deaths attributed to acute alcohol poisoning and chronic alcoholism.

The concentrations of ethanol were determined in femoral venous blood (BAC) and urine (UAC) and the UAC/BAC ratios were evaluated for a large case series of forensic autopsies in which the primary cause of death was either acute alcohol poisoning (N=628) or chronic alcoholism (N=647). In alcohol poisoning deaths both UAC and BAC were higher by about 2g/l compared with chronic alcoholism deaths. In acute alcohol poisoning deaths the minimum BAC was 0.74 g/l and the distribution of UAC/BAC ratios agreed well with the shape of a Gaussian curve with mean+/-standard deviation (S.D.) and median (2.5th and 97.5th centiles) of 1.18+/-0.182 and 1.18 (0.87 and 1.53), respectively. In alcoholism deaths, when the BAC was above 0.74 g/l (N=457) the mean+/-S.D. and median (2.5th and 97.5th centiles) UAC/BAC ratios were 1.30+/-0.29 and 1.26 (0.87 and 2.1), respectively. When the BAC was below 0.74 g/l (N=190), the mean and median UAC/BAC ratios were considerably higher, being 2.24 and 1.58, respectively. BAC and UAC were highly correlated in acute alcohol poisoning deaths (r=0.84, residual S.D.=0.47 g/l) and in chronic alcoholism deaths (r=0.95, residual S.D.=0.41 g/l). For both causes of death (N=1275), the correlation between BAC and UAC was r=0.95 and the residual S.D. was 0.46 g/l. The lower UAC/BAC ratio observed in acute alcohol poisoning deaths (mean and median 1.18:1) suggests that these individuals died before absorption and distribution of ethanol in all body fluids were complete. The higher UAC/BAC ratio in chronic alcoholism (median 1.30:1) is closer to the value expected for complete absorption and distribution of ethanol in all body fluids.

Alcoholism↗

Comparison of blood-ethanol concentration in deaths attributed to acute alcohol poisoning and chronic alcoholism.

Ethanol concentrations were measured in femoral venous blood in deaths attributed to acute alcohol poisoning (N = 693) or chronic alcoholism (N = 825), according to the forensic pathology report. Among acute alcohol poisonings were 529 men (76%) with mean age 53 years and 164 women (24%) with mean age 53 years. In the chronic alcoholism deaths were 705 men (85%) with mean age 55 years and 120 women (15%) with mean age 57 years. The blood-ethanol concentrations were not related to the person's age (r = -0.17 in acute poisonings and r = -0.09 in chronic alcoholism). The distribution of blood-ethanol concentrations in acute poisoning cases agreed with a normal or Gaussian curve with mean, median, standard deviation, coefficient of variation, and spread of 0.36 g/100 mL, 0.36 g/100 mL, 0.086 g/100 mL, 24% and 0.074 to 0.68 g/100 mL, respectively. The corresponding concentrations of ethanol in chronic alcoholism deaths were not normally distributed and showed a mode between 0.01 and 0.05 g/100 mL and mean, median, and spread of 0.172 g/100 mL, 0.150 g/100 mL, and 0.01 to 0.56 g/100 mL, respectively. The 5th and 95th percentiles for blood-ethanol concentration in acute poisoning deaths were 0.22 and 0.50 g/100 mL, respectively. However, these values are probably conservative estimates of the highest blood-ethanol concentrations before death owing to metabolism of ethanol until the time of death. In 98 chronic alcoholism deaths (12%) there was an elevated concentration of acetone in the blood (>0.01 g/100 mL), and 50 of these (6%) also had elevated isopropanol (>0.01 g/100 mL). This compares with 28 cases (4%) with elevated blood-acetone in the acute poisoning deaths and 22 (3%) with elevated blood-isopropanol. We offer various explanations for the differences in blood-ethanol and blood-acetone in acute poisoning and alcoholism deaths such as chronic tolerance, alcohol-related organ and tissue damage (cirrhosis, pancreatitis), positional asphyxia or suffocation by inhalation of vomit, exposure to cold coupled with alcohol-induced hypothermia, as well as various metabolic disturbances such as hypoglycemia and ketoacidosis.

2-Propanol↗

Coexistence and concentrations of ethanol and diazepam in postmortem blood specimens: risk for enhanced toxicity?

Both ethanol and diazepam are classified as depressants of the central nervous system and exert their effects via the GABAA receptor complex. We report the coexistence and concentrations of ethanol, diazepam, and its primary metabolite nordiazepam in a case series of 234 forensic autopsies collected over a ten-year period. Diazepam, nordiazepam, and ethanol were determined in femoral venous blood by highly selective gas chromatographic methods. The mean (median) femoral blood concentrations were ethanol 0.24 g/100 mL (0.25 g/100 mL), diazepam (D) 0.23 microg/g (0.10 microg/g), nordiazepam (ND) 0.24 micro/g (0.20 microg/g), sum (D + ND) 0.43 microg/g (0.30 microg/g), and the ratio D/ND was 1.19 (1.0). When cause of death was attributed to alcohol and/or drug intoxication (N = 50), the mean and median blood-ethanol concentration was higher, being 0.36 g/100 mL and 0.38 g/100 mL, respectively, whereas the mean (median) and range of blood-diazepam concentrations were about the same, 0.23 microg/g (0.10 microg/g) and 0.05 to 1.2 microg/g. The femoral-blood concentrations of diazepam and nordiazepam were highly correlated (r = 0.73), but there was no correlation between the concentrations of ethanol and diazepam (r = -0.15). In another 114 fatalities (all causes of death) with diazepam and/or nordiazepam as the only drugs present, the mean (median) and range of blood-diazepam concentrations were 0.22 microg/g (0.10 microg/g) and 0.03 to 3.5 microg/g. The pathologists report showed that none of these deaths were classed as drug intoxications. The impression gleaned from this study of ethanol-diazepam deaths is that high blood-ethanol concentration is the major causative factor. We found no evidence that concurrent use of diazepam enhanced the acute toxicity of ethanol, although interpretation is complicated by the high blood-ethanol concentration (median 0.38 g/100 mL), making it difficult to discern an added effect of diazepam.

Central Nervous System Depressants↗

Fatal poisoning in drug addicts in the Nordic countries.

The study includes medicolegally examined fatal poisonings among drug addicts in 1997 in the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden, and the results are compared to a similar investigation from 1991. A common definition of "drug addict" was applied by the participating countries. The highest death rate by poisoning in drug addicts was observed in Denmark, where it was 6.54 per 10(5)inhabitants, followed by Norway with 6.35, Sweden with 2.21, Finland with 1.63 and Iceland with 1.20 per 10(5)inhabitants. All countries showed a higher death rate in 1997 than in 1991. For all countries the distribution of deaths according to geographical regions showed a decreasing number of drug deaths in the metropolitan area and an increasing number in other cities. Heroin/morphine dominated as the cause of death and was responsible for about 90% of the cases in Norway. In Sweden and Denmark, however, heroin/morphine caused only about 70% of the fatal poisonings. About 30% of the fatal poisonings in Denmark and Sweden were caused by other group I drugs, in Denmark mainly methadone and in Sweden mainly propoxyphene. Apart from two cases in Sweden methadone deaths were not seen in the other Nordic countries. In Finland heroin/morphine deaths have increased from about 10% in 1991 to about 40% in 1997. Forty-four percent of the fatal poisonings in Finland were caused by other group I drugs, mainly codeine and propoxyphene. The two fatal poisonings in Iceland were caused by carbon monoxide. Only few deaths in this investigation were caused by amphetamine and cocaine. A widespread use of alcohol, cannabis and benzodiazepines, especially diazepam, was seen in all the countries.

Adolescent↗

Flunitrazepam: an evaluation of use, abuse and toxicity.

The benzodiazepine flunitrazepam is extensively prescribed to patients with insomnia in many countries, but has also become popular among alcohol- and drug abusers. Several reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. Furthermore, flunitrazepam is involved in many fatal intoxications in Sweden. This study was designed and conducted to explore the negative consequences of flunitrazepam abuse in Sweden, and to assess the trends in its use and abuse. The occurrence of flunitrazepam in cases referred to the Department of Forensic Chemistry in Linköping, Sweden 1992-1998, was investigated in detail. The detections were studied separately for different groups; medicolegal death investigations, drug abuse cases, driving under influence cases, and other medicolegal cases. These data were further compared with the sales, and seizures by the Swedish Customs and the Swedish Police. During 1992-1998, 641 fatalities occurred, where the cause of death was attributed to intoxication with flunitrazepam solely (130) or in combination with other drugs, or concomitant conditions (511). In 78% of all driving under influence cases, where flunitrazepam was detected, the analyses also disclosed the presence of illicit drugs. A similar association was seen in drug abuse cases. The seizures reported by the Swedish Customs revealed a substantial and increasing illegal trade. Cases, where flunitrazepam seemingly induced violent behavior were identified, and one of these is described in some detail. It is concluded that the abuse pattern and the toxicity of flunitrazepam should be kept in mind by forensic investigators and that this panorama also should be considered when decisions about the registration and classification of flunitrazepam are made in different countries.

Anti-Anxiety Agents↗

Postmortem measurements of thyroid hormones in blood and vitreous humor combined with histology.

The aim of this study was to investigate whether clinical reference premortem values can be used to assess postmortem concentrations of thyroxine, triiodothyronine, and thyroid stimulating hormone (TSH), to compare the postmortem concentrations in blood and vitreous humor, and to study the possibility of diagnosing hyperthyroidism by comparing thyroid histologic appearance and postmortem hormone values. Biochemical analyses of free thyroxine (FT4), free triiodothyronine (FT3), and TSH in femoral blood and vitreous humor were made in 38 cases. In 40 cases, the hormones and thyroid histologic appearance were studied; 22 had no significant pathologic changes, and 18 showed focal hyperplasia of the follicular epithelium. A positive correlation was seen between the femoral blood and vitreous humor concentrations of FT4 (R = 0.66) but not between the corresponding concentrations of FT3 and TSH. A positive correlation was also seen between FT3 and FT4 in femoral blood (R = 0.74). In cases with normal thyroid histologic appearance, 58% were found to have FT4 values >24 pmol/L (clinical reference interval 9-24 pmol/L), mean value 27.5 +/- 9.4 pmol/L), which did not differ from the FT4 values in the cases with hyperplasia, 31.6 +/- 15 pmol/L. Only 5% of the T3 measurements in the group with normal histologic appearance were >9 pmol/L (clinical reference interval 3-9 pmol/L). The mean value of FT3 in cases with normal histologic appearance was 3.4 +/- 1.3 pmol/L, and in the group with hyperplasia 8.6 +/- 6.1 pmol/L. The difference was statistically significant P < .005). It is concluded that postmortem values of FT3 and FT4 in femoral blood are fairly comparable to premortem clinical reference values, but the upper normal limit, especially for T4, has to be adjusted upward. Analysis of vitreous humor cannot be used post mortem to assess thyroid function. Histologically, hyperplastic changes correlate well with elevated FT3 in femoral blood.

Adult↗

Uncertainty in estimating blood ethanol concentrations by analysis of vitreous humour.

AIMS: To determine the concentrations of ethanol in femoral venous blood (FVB) and vitreous humour (VH) obtained during forensic necropsies. The ratios of ethanol concentrations in VH and FVB, the reference interval, and the associated confidence limits were calculated to provide information about the uncertainty in estimating FVB ethanol concentrations indirectly from that measured in VH. METHODS: Ethanol concentrations were determined in specimens of FVB and VH obtained from 706 forensic necropsies. The specimens were analysed in duplicate by headspace gas chromatography (HS-GC), with a precision (coefficient of variation) of 1.5% at a mean ethanol concentration of 500 mg/litre. The limit of detection of ethanol in body fluids by HS-GC in routine casework was 100 mg/litre. RESULTS: In 34 instances, ethanol was present in VH at a mean concentration of 154 mg/litre, whereas the FVB ethanol concentration was reported as negative (< 100 mg/litre). These cases were excluded from the statistical analysis. The concentration of ethanol in FVB was higher than in VH in 93 instances, with a mean difference of 160 mg/litre (range 0 to 900). The mean concentration of ethanol in FVB (n = 672) was 1340 mg/litre (SD, 990) compared with 1580 mg/litre (SD, 1190) in VH. The arithmetic mean VH/FVB ratio of ethanol was 1.19 (SD, 0.285) and the 95% range was 0.63 to 1.75. The mean and SD of the differences (log VH - log FVB) was 0.063 (SD, 0.109), which gives 95% limits of agreement (LOA) from -0.149 to 0.276. Transforming back to the original scale of measurement gives a geometric mean VH/FVB ratio of 1.16 and 95% LOA from 0.71 to 1.89. These parametric estimates are in good agreement, with a median VH/FVB ratio of 1.18 and 2.5th and 97.5th centiles of 0.63 and 1.92. CONCLUSIONS: The ethanol distribution ratios (VH/FVB) show wide variation and this calls for caution when results of analysing VH at necropsy are used to estimate the concentration in FVB. Dividing the ethanol concentration in VH by 2.0 would provide a very conservative estimate of the ethanol content in FVB, being less than the true value, with a high degree of confidence.

Autopsy↗

Cytochrome P450 2D6 (CYP2D6) genotyping on postmortem blood as a supplementary tool for interpretation of forensic toxicological results.

Debrisoquine hydroxylase (CYP2D6) is involved in the metabolism of many toxicologically important drugs. The gene encoding for this enzyme displays a polymorphic distribution in all populations examined. We report a study on 46 cases, where analyses of the CYP2D6 gene were conducted on postmortem femoral blood in order to investigate the occurrence of poor metabolizers (PM). A polymerase chain reaction (PCR) method, designed and routinely used for therapeutic drug monitoring, was employed, only slightly modified. Samples from 22 cases, where the parent drug to metabolite ratio was unexpectedly high were analyzed as well as samples from 24 control cases. Genotyping could be carried out in all but one case. Previous freezing or addition of potassium fluoride as preservative did not prevent analysis. Only one PM (from the control group) was discovered, implying an occurrence of only 2.2% as compared to the reported frequency of approx. 7% in Sweden. Among the extensive metabolizers (EM), however, a number of individuals with mutated genes were identified. Although it seems reasonable to suspect a PM genotype in cases with a high concentration of a drug metabolized by CYP2D6, but without suspicion of acute overdose, our study does not support the opinion that this interpretation pitfall is particularly common. This study rather indicates that drug interactions in EMs constitute a more frequent and important problem.

Adult↗

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.

Adult↗

Psychotropics and suicide prevention. Implications from toxicological screening of 5281 suicides in Sweden 1992-1994.

BACKGROUND: Systematic clinical investigations of consecutive suicides have found psychiatric disorders in 90-95% of subjects (depressive disorder 30-87%). AIMS: To investigate use of psychotropics in men and women of different ages who commit suicide. METHOD: Results of toxicological screening in 5281 suicides in Sweden 1992-94 were studied. RESULTS: Psychotropics were detected in 45.3% of the suicides. Antidepressants were detected in 12.4% of the men and 26.2% of the women (7.2% and 14.2%, respectively, of those under 30 years of age). Neuroleptics or antiepileptics (in the absence of antidepressants) were detected in 8.3%, and anxiolytics/hypnotics alone in 20.5% of the subjects. Overdose by an antidepressant was the probable cause of death in 2.1% of the men and 7.9% of the women. CONCLUSIONS: The pattern of psychotropics detected in toxicology was incongruent with the pattern of diagnoses found in the clinical investigations of suicides mentioned above. Depression appears to be under treated in individuals committing suicide, especially in men and in subjects under 30 years of age.

Adolescent↗

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.

Acetaminophen↗

Fatal injections of heroin. Interpretation of toxicological findings in multiple specimens.

We report two fatalities due to injection of heroin. The first case was witnessed but during the early phase of the police investigation the question was raised whether the injection was self-administered. Multiple samples were collected from different sites and analysed in order to establish drug distribution and to determine the site of injection. Fresh injection marks were found in both antecubital fossae but histological examination failed to settle which one was the last. However, toxicological analysis of the tissues at the injection sites indicated that the injection in the right arm was the last one. This was consistent with the suspicion that the victim was given the injection by another person although probably in agreement with the deceased. In the second case, a similar toxicological procedure was used. This fatality was not witnessed, however ample evidence indicated that it was an isolated event in a former intravenous heroin addict and there was only one fresh injection mark. Even in this case, the concentration of morphine was much higher in the tissue sample from the injection mark than in any of the blood samples.

Adult↗

A cluster of fentanyl-related deaths among drug addicts in Sweden.

During a 16-month period, nine fatalities occurred among white male drug-addicts, where fentanyl was detected at postmortem toxicological analysis. The street samples associated with these cases confirmed the presence of fentanyl as an additive in low-concentration amphetamine powders with caffeine, phenazone and sugar as cutting agents. In seven of the cases, an acute intoxication by fentanyl was considered to be the immediate cause of death, and in one case, it was likely, but no analysis of fentanyl was performed in blood, and in another case the death was suicide by hanging. This appears to be the first report of a cluster of fentanyl-related deaths outside the United States, and the occurrence of fentanyl in combination with amphetamine has not previously been reported. In addition, in all cases, femoral blood was collected, and samples were handled and analysed according to standardized, quality-controlled procedures. The previous history, circumstances surrounding the death, autopsy findings, histology and toxicology examination of each case are presented. The gas chromatographic-mass spectrometric method for fentanyl is also described. Fentanyl concentrations ranged from 0.5 to 17 ng g-1 blood, and from 5 to 160 ng ml-1 urine. Other drugs found were amphetamine (8 cases), ethanol (5 cases) and benzodiazepines (5 cases). Morphine was found in only one case. The average age of men was 33.9 years (range 22-44); six were found in their own of friend's apartment, two inside buildings (stairways) and one was found outdoors. We conclude that fentanyl is a dangerous substance that should be considered in drug-addict deaths even outside the United States, particularly when the remaining toxicology is unremarkable, and the cause of death cannot be ascertained

Adult↗