ยินดีต้อนรับ

สถาบันนิติเวชวิทยา มีเจตจำนงแน่วแน่ที่จะพัฒนาองค์กรให้ทันกับความต้องการเทคโนโลยีทาง นิติเวชศาสตร์ เพื่อสนองตอบต่อความต้องการของกระบวนการยุติธรรม ในการป้องกันและตรวจจับการกระทำผิดต่อร่างกายและชีวิต

  • header1.jpg
  • header2.jpg
  • header3.jpg

You are here:

Toxicological and Pathological patterns of Caucasians died for heroin in Thailand

Toxicological and Pathological patterns of Caucasians died for heroin in Thailand 

Abstract

This purpose of this study is to determine the toxicological and pathological patterns of Caucasians died from heroin in Thailand. Retrospective review of 22 heroin-related Caucasian deaths from reports obtained from pathology division of Institute of Forensic Medicine, Police Hospital, Bangkok, from January 2007 to May 2010. The finding patterns are compared with patterns from 14 Caucasian cases in which morphine are incidental found and also 36 control Caucasian deaths in which toxicology screening is negative. Results; the mean age of heroin-related Caucasian deaths is 15.71 years younger than patient group. The heroin related group whose brain and lung weights are significantly more than those of patient and control group. The prominent toxicological pattern is concomitant consumption of other drugs (especially alcohol and benzodiazepine).Conclusions: Systemic diseases play significant roles in these heroin-related deaths. On the other hand, some pathological patterns are consequences of  heroin toxicity and complications of infection and contaminated substances induced by injection.

 

INTRODUCTION

          Opiate abusers have an increased mortality rate of approximately 13 times compared with non-abusing peers, it has been estimated that heroin abusers lose about 18 years of potential life due to premature death before the age of 65.1)

            In the EU, opiate abuse results in approximately 8,000 deaths each year. Forensic records estimate that 300 to 400 drug related deaths occur each year in Sweden and that half of them are attributed to opiates.2)

            Most people who died from Opiate toxicity in Thailand at the present are Caucasian (white foreigners) who stays in Thailand, while Thai people rarely died from this cause.

            The primary mechanism of death is opioid-induced respiratory depression, although hypoxia-induced cardiac arrest and arrhythmia may also occur 3–5).

            The characteristics of opiate overdose can be explained partially in terms of poly-drugs use. The overwhelming majority of opiate overdoses involve the concomitant consumption of other drugs, particularly alcohol, benzodiazepines, tricyclic antidepressants and cocaine 6). Alcohol and benzodiazepines, the most commonly detected drugs, are central nervous system (CNS) depressants, as are opiates. It is likely that  the respiratory depressant effect of these drugs increases when taken with an opiate, which may partially explain the low morphine concentrations seen in many cases.

            Morphine is an opiate analgesic which itself is abused, but is more frequently found as a metabolite of heroin (diacetylmorphine). After administration, heroin rapidly hydrolyses in whole blood to 6-monoacetylmorphine (6-MAM), which in turn is further metabolized to morphine and a few of codeine. In this study, addiction cases were restricted to the heroin deaths where both morphine and 6-monoacetylmorphine (6-MAM) were presented in specimen. The presence of 6-MAM was selected as an inclusion criterion, as its presence confirms the intake of heroin prior to death.7)

                Recent research has demonstrated high levels of systemic disease amongst fatal opiates overdose cases 8). There are good reasons to suppose that disease may play a significant role in such deaths. Cardiac damage, for instance, may increase susceptibility to the effects of opiates induced hypoxia, whilst liver disease may increase overdose risk due to poorer metabolism. As with toxicology, no study has directly compared the systemic disease of heroin-related overdose cases.

The current study aimed to determine the differences in the toxicological and pathological patterns of deaths involving heroin toxicity in fatal Caucasian cases who travel to Thailand.

MATERIALS AND METHODS

Autopsy reports of Caucasians were obtained from pathology division of Institute of Forensic Medicine, Police Hospital, The Royal Thai Police Headquarter, Bangkok (IFM) and toxicological reports were obtained from toxicology division of IFM, from January 2007 to May 2010. Screening Urine analysis for Opiates constituents with Dimension PxL (™) screening equipments (cut-off 300 ng/ml). Positive screenings were confirmed by using liquid chromatography - electrospray ionization - time of flight mass spectrometry (LC-ESI-TOF-MS).

The cause and manner of death were reviewed to determine whether death was related to opiates (heroin, morphine) and toxicity (drug related or addict group) or whether opiates was merely an incidental finding (patient group). Drug-related deaths were defined as those in which a direct toxic effect of opiates caused or contributed to death.

Findings in cases classed as being drug related were compared with findings from cases in which morphine was incidental and also with findings from a group of 36 controls in which toxicology screening was negative. Furthermore, gender and age (±5 years) are used as the criteria for selected controls.

RESULTS

Demographic findings

          A total of 36 Caucasians cases in which morphine had been detected were identified out of 945 cases processed by our medical examination during that period. Frequency of gender difference and mean age of case-control samples are shown in Table 1.

            The decedents were predominantly male (35/36, or 97.2%). The mean age of the 22 cases whose deaths were deemed to have been drug related was 42.50 years. The mean age of the 14 cases whose deaths were deemed not to have been drug related was 58.21 years. By one way ANOVA test, finding that these three groups have significant mean difference (p = 0.000) From Scheffe Post Hoc Tests, the mean difference between addict cases and patient cases are significantly different (15.71, standard error 3.62, p=0.000). This test also found that the mean difference between addict cases and control are significantly different too, while the mean difference between patient cases and control are not significantly different (7.49, standard error 3.37, p=0.093)

Table 1 Gender and age difference in samples

 

n

Gender

 

Age

Female (%)

Male (%)

 

Mean

S.D.

Minimum

Maximum

Patient Cases

14

2 (14.3%)

14 (85.7%)

 

58.21

9.40

38

69

Addict Cases

22

0

22 (100.0%)

 

42.50

8.30

26

58

Controls

36

1 (2.8%)

35 (97.2%)

 

50.73

12.23

26

72

Anatomical and medical findings

          Table 2 shows the mean weight of the Brain, Right Lung, Left Lung, Heart, Liver, Spleen, Right Kidney and Left Kidney of the 36 cases in which opiates (morphine) was detected and in 36 controls. The weight of each organ of addict cases were seemingly increased in all cases compare with another groups. When used one way ANOVA testing data of each organ, finding that brain, right lung and left lung are significant difference (p=0.006,p=0.009 and p=0.008 respectively)

Table 2 Weight of organs at postmortem examination in 36 cases in which morphine was detected and in 36 controls in which toxicology screening was negative

Group

Mean and (Standard Deviation) weight (g)

Brain

Right Lung

Left Lung

Heart

Liver

Spleen

Right Kidney

Left Kidney

Controls  

n = 36

1430.61

(136.24)

753.33

(167.12)

659.70

(155.65)

468.79

(99.40)

1901.21

(511.23)

208.79

(96.66)

198.79

(57.16)

195.94

(43.69)

Patient Cases

n = 14

1406.43

(130.72)

758.57

(231.91)

635.71

(186.82)

421.43

(127.82)

2013.57

(649.20)

208.57

(130.14)

177.86

(69.08)

181.43

(74.61)

Addict Cases

n = 22

1533.18*

(115.57)

911.82*

(198.03)

779.09*

(176.98)

456.36

(88.67)

2188.18

(510.14)

242.27

(164.03)

186.36

(51.13)

186.36

(59.81)

Patient Cases : Cases in which morphine was incidental,  Addict Cases : Cases in which death was morphine related, *P < 0.05 for comparison with controls.

         

          The pathological finding details of 22 Addict cases are shown in Table 3.    

Table 3 Pathological finding on postmortem examination in 22 addict cases.

Pathological finding

Organs

Findings

cases

Organs

Findings

cases

Brain

Neuronal necrosis

3

Hepatic

Lymphocytic infiltrate

6

Infraction

2

Steatosis

7

Cardiac

Ventricular hypertrophy

10

Fibrosis

3

Myocardial fibrosis

2

Cirrhosis

2

Myocarditis&Endocarditis

2

Necrosis

1

Atherosclerosis

10

Renal

Nephrosclerosis

9

Pulmonary

Bronchopneumonia

4

Fibrosis

1

Lobarpneumonia

2

Others

Skin lesion

4

Pulmonary granuloma

1

Angiitis

1

Emphysema & Empyema

1

Body packer syndrome

1

Toxicological findings

            From the toxicological analysis, founding that one of 22 addict cases use only heroin, but the others were a cocktail use of many drugs, as shown in table 4.  

Table 4.  Other drugs detected in postmortem urine samples in 22 addict cases.

Other drugs

Type of Drugs

cases

0 drug

No other drug

1

1 drug

Alcohol

6

Benzodiazepines

3

Sildenafil

1

2 drugs

Alcohol + Benzodiazepines

1

Alcohol + Cocaine

1

Alcohol + Paracetamol

1

Tricyclic Antidepressants + Paracetamol

1

Methamphetamine + Benzodiazepine

1

Methadone + Benzodiazepine

1

3 drugs

Alcohol + Methamphetamine + Benzodiazepines

1

Methadone + Cocaine + Sildenafil

1

Methadone + Benzodiazepines + Tricyclic Antidepressants

1

4 drugs

Methadone + Benzodiazepines + Tricyclic Antidepressants + Tramadol

1

Methamphetamine + MDMA + Ketamine + Benzodiazepines

1

Discussion

Heroin purity is an aetiological factor in heroin overdose.[9] The classical depiction of a fatal ‘overdose’, as the result of a quantity or quality (purity) of heroin in excess of the person’s current tolerance to the drug, is the most long-standing and widely accepted explanation for death due to heroin. A natural consequence of this view is that fluctuations in heroin purity (the diacetylmorphine content of the drug) are seen as a major cause of heroin-related deaths. Furthermore, heroin users themselves believe that variations in purity are the major cause of non-fatal and fatal overdoses 10).

            Nowaday, Thailand was still used as a transit country in smuggling heroin from the Golden Triangle and the Golden Crescent to other countries. Some was retailed for the European and American tourists. Heroin which obtained from Thailand was high purity (purity range 78.1 - 85.5%) compared with 31.0 - 53.0% of United Kingdom heroin’s purity and 0.1 - 89.0% of United State heroin’ purity. 11) Thus if heroin abuser take in the same quantity, it will get high content of diacetylmorphine, and  overdose of taking can be the cause of death.

In this study finding that 95.5% of fatal addict cases are poly-drugs use, 45.5% are positive alcohol and benzodiazepines. The concomitant use of heroin with the central nervous system depressants alcohol 12-14), and benzodiazepines 14,15) is associated with the majority of ‘heroin’ overdoses. 

Alcohol was the only accompanying substance associated with lower heroin blood levels. Where alcohol was detected, levels were between 20 - 50 percent lower, suggesting that concurrent alcohol use reduces the lethal heroin overdose threshold by as much as half. In another hand, other substances frequently detected in cases of heroin overdose do not appear to show this effect. If benzodiazepines have a causative role in fatal heroin overdoses, it is not through this mechanism. 16)

Phillip et al. 2007 17) finding that the high prevalence of concurrent benzodiazepine detections in opiates-related fatalities represents a genuine risk factor for opiates overdose rather than simply being a feature of these deaths and as such implicates benzodiazepines in the causal pathway of fatal opiates overdose. However, in order to validate this finding it is necessary to impose more rigorous criteria than simply association alone. In addition to association, two of the main criteria for causality are biological plausibility and a dose-response relationship. Although these are not essential for causality to be demonstrated, they provide a useful guide for us to assess the role of benzodiazepines within the context of the present findings and the existing knowledge base. Furthermore, Philip et al. indicate that opiates users who also use benzodiazepines have an increased risk of fatal overdose (OR = 10.27: 95% Cl 5.53–19.08, χ2 = 97.61 (P<0.001)). Heroin metabolites or methadone are potent respiratory depressants, exerting their effects at various sites within both the central and peripheral nervous systems. While pulmonary edema is frequently observed in opiates overdose, it is the depression of respiration that is thought to be the most common cause of death 18).

             Cocaine use may be associated with an increased risk of non-fatal opiates overdose. One study for example, found that cocaine user had a 1.8 times greater risk of experiencing a nonfatal overdose than those without evidence of cocaine use (Taylor et al., 1996). But, Phillip et al. finding that cocaine dose not play a role in this study, the estimated relative risk of heroin fatal overdose for those with evidence of recent use of cocaine was 0.26.

In this study, concomitant with cocaine 2 cases, the first take cocaine with heroin and alcohol, another one take heroin, methadone and cocaine. The other substances which are increase the action of drug which can cause the death may obtain from alcohol and methadone.

Brain Pathology

This study exibits less to mark nonspecific hypoxic brain injury(hypoxic encephalopathy) as brain edema or/and vascular congestion to necrosis. Most cases should die so rapidly that no morphologic evidence become apparent even with the use of immunohistochemical staining. The injury seen are not so much from a result of  hypoxia but rather a result of ischemia caused by hypotension that ensues due to hypoxia. Only visible two infarct cases and three cases of definite neuronal necrosis are reported. There have been several suggested mechanisms for acute ischemia in heroin users, including vasospasm, vasculitis, hypersensitivity reaction, hypoventilation and embolic ischemia. Vasospasm might be related to constrictor effect of the ų receptor on vascular smooth muscle. While vasculitis might be attributed to immune response and direct vascular injury.19) In some studies, hypersensitivity  reaction is found in reexposed heroin patients after a long-time abstinence.[19] Some cases with border zone infarcts are thought to be associated with hypoventilation and poor perfusion during acute heroin intoxication 6,16-18). Embolization might be related to insoluble particle in the intravenous injection. Except perivascular pigment deposition within macrophages, which  is probably  the result of repeated intravenous injection of foreign materials. No one lesion is diagnostic for narcotic abuse, at least not at the light microscopic level. When abnormalities are visible, they are almost always consequence of  some infection process acquired during the process of heroin infection.4) Except only one case of cerebral angiitis, which is not diagnostic for morphinism is reported. Other better known neuropathologic complications of narcotic abuse, for example, spongioform leucoencephalopathy, complication of endocarditis, complication of HIV infection, rhabdomyolysis and parkinsonism are not reported in this review.

Pulmonary Pathology

This study reveals that both lungs of most cases apparently gain more weights than those of patients and control cases due to pulmonary edema. By clinical study, pulmonary edema complicating heroin-overdose is a well recognized entity and regarded as a major mechanism contributing to death in heroin abuser. The onset of clinically apparent pulmonary edema occurs  during 12-24 hours following recovering from the heroin-induced coma.20)

            Narcotic related pulmonary edema was first observed by a DR Lee in New York in the 1950s. Until now, the definite mechanism remains unclear. Many studies attribute pulmonary to hypoxia-induced increase in pulmonary capillary permeability 20),although there is arguing notion suggesting that this is related to hypersensitivity to heroin or adulterants especially in non-overdose fatal cases. Since the edema fluid associated with narcotic overdose is rich in protein, foaming may first be seen at  mouth and nostrils of the dead body. This foaming occurs when the obvious pulmonary edema fluid looking like beaten egg whites exudes from the upper airway and even out of the mouth and nares during agonal respiratory effort.

            Six cases diagnosed as pneumonia from this study are microscopically identified as four cases of acute bronchopneumonia and 2 cases of lobar pneumonia. Three from four cases of bronchopneumonia have aspirated contents mixed with marked secretion. In addition, moderate degrees of blood alcohol are found in these cases. Aspiraton pneumonia has straightforwardly more tendency to occur when cough reflex and level of consciousness are depressed by intoxication of narcotic and alcohol. One case of lobar pneumonia complicated with empyema encouters emphysema and septisemia. Emphysema changes are occasionally seen in the subset of intravenous abusers who inject medications meant for oral use, and are more common in stimulant drug abuser. Typically, these changes mostly damage the upper lobe, however all lobes affected in this case should be due to smoking. [19] In the standpoint of septicemia, many studies indicate that the cause of higher rate of septisemia in intravenous drug users than normal population is unsterilied materials through contaminated syringes, while empyema which may even be the first evidence of infection in such individual is more likely to be developed in HIV infected heroin abuser. 

            Pulmonary granuloma including right heart hypertrophy, cerebral angiitis and many tract marks sites is found  in one case. Metabolites of midazolam and codeine which are prevalent non-prescription illegally distributed in Thailand street incidentally exist in these urine samples as well. Repeat injections of oral particulate material used as pharmaceutical filler to magnify drug size will trap at the branch points small arteries. Organization and recanalization of thrombi at this pulmonary arteries look like plexiform lesions of primary pulmonary and lead to right ventricular hypertrophy. Besides magnesium triciliate used in pharmaceutical industry as a filler, there are many foreign substances which are the culprits such as cotton, starch or cellulose.         

Cardiac Pathology

            It is not certain that the heart disease more frequently occurs among opiate abusers than control cases 4). Some underlying and induced cardiac disease found with opiate abuse in this review will be discussed as follow.             

            First, why ventricular hypertrophy in intravenous heroin abusers is a common concomitants finding can be due to contaminating pulmonary vascular bed-laden substances and potentiating sympathetic effect of simultaneous stimulant drugs injected, in addition to habitual cigarette smoking.

            Second, in this study, coronary artery atherosclerosis is the other prominent pathologic cardiac findings besides ventricular hypertrophy. Whether the incidence of coronary artery disease in heroin addicts is different from that in aged-matched controls is still in doubt. Previous hypotheses explain that heroin might have a direct effect on the coronary artery and induces acute coronary occlusion, either by provoking a local coronary artery spasm or inflammation. Some studies have suggested that heroin act directly on the vasomotor center to increase parasympathetic activity and stimulate the release of histamine from mast cells, thus resulting in bradycardia and hypotension. Both mechanisms might have contributed to acute myocardial infarction. On the other hand, other some studies attribute relative scarcity of heart diseases (excluding endocarditis in intravenous drug users) comparing to those of nonaddicts may be due to the cardioprotective effects of heroin/morphine. The mechanism involves the process known as “preconditioning”. If the heart exposed to sublethal myocardial ischemia, it is actually protected from later, severe ischemia insults for up to 72 hours. During the first 24 hours myocardial protection is conferred by the increased production of inducible nitric oxide. During longer phase, protection is the result of increased cyclooxygenase-2(COX2) production

            Third, two myocardial infarction cases are presented in this study. Ones are 35 and 54 years old. The older 54-year-old whose causes of atherosclerotic may be smoking, hypertension and even direct effect of opiate.

Fourth, in the standpoint of endocarditis ,the younger  case of myocardial infarction(focal fibrosis) which  apparently presented with endocarditis and focal myocarditis exhibits common causative skin lesion  producing these conditions such as some fresh and recent needle punctures on both antecubital fossas and track mark on left wrist . In addition to vegetations on tricuspid and pulmonic valve which are more often involved more than in addicts than in the general population, probable hepatitis-C induced generalized hepatic lymphatic infiltration also presented in this case. After HIV pandermic in the last two decades, infective endocarditis is the only other cardiovascular disease of which the incidence is clearly higher among intravenous drug users. 

Hepatic Pathology

This study finds prominently pulmonary edema, cardiac disease, and liver disease, to be common among cases of fatal opiates toxicity.8) Both most prominent pathologic hepatic findings as lymphocyte infiltrate and steatosis are reported like  previous ubiquitous studies.  While some types of liver disease such as fibrosis and cirrhosis are particularly pronounced among elder cases. Findings of lymphocytic infiltrate in the portal tracts of addicts are in the preponderance of younger group (particularly long-term intravenous drug users) . In spite of serostatus unproved in this study, Hepatitis C virus significantly plays role in causing addicts’ hepatic findings due to high rate of nationwide infection among intravenous opiate users.  Different demographic pattern among any population  may be explained by how difference risk of elder hepatic injury due to poor hepatic metabolism, and repeat drug effect of chronic elderly abusers, and prolong time which chronic hepatitis C take to culminate in fibrosis, cirrhosis and even carcinoma is. Beside long-term effects of HCV that can result in specific types of liver disease presented in this review. Liver damage in the addict population has always been attributed to the combination of lifestyle (e.g. smoking, alcohol consumption and malnutrition) and possibly some toxic effects exerted by drug injected. Evidence of hepatic fibrosis, fatty change and mixed cellular lobular infiltrate may be seen in the early stage of HCV infection. Cirrhosis found in 2 elderly cases is late stage derived from any varied causes. Only one case of uncommon scattered hepatic cell necrosis is as uncommonly found as other previous studies. Whatever the cause, reduced opiate metabolism among liver-damaged opiates user renders more susceptibility to overdose toxicity.

Renal Pathology

Levels of renal disease are low comparing with other pathological systems. Five cases

older than 54 years old are notably diagnosed with nephrosclerosis and/or fibrotic scarring which are the general pictures of poor health among the older opiate users. The factors determining individual susceptibility to renal diseases remain poorly understood, and it is not always clear whether the drugs injected or some other factors are responsible or not. The disease may, however, be relevant to overdose risk due to resultant strain upon the cardiovascular system. Once(in the early 1970s),the relentless progressive nephritic syndrome that was unresponsive to therapy and terminated in renal failure within a few months to a few years frequently occurred in heroin abusers in U.S. 4) The predominant histologic alteration in this individual  is focal segmental glomerulosclerosis which is believably caused by immune-mediated process. However, FSGS can also be in conjunction with many difference disorders; immune-complex mediated injury, hypertension, obesity, diabetes, reflux nephropathy, chronic interstitial nephritis and human immunodeficiency virus.[4] Once the clinical diagnosis of FSGS has been made among narcotic abusers, the pattern presented must be distinguished from other possible disease types. These diseases are membranoproliferative glomerulonephritis, renal amyloidosis necrotizing angiitis with renal involvement interstitial nephritis and acute tubular necrosis due to rhabdomyolysis. In this review, except 3 nephrosclerotic cases and only one case of cerebral with renal angiitis. Other diseases are not diagnosed due to difficulty of glomerulonephritis diagnosis with the light microscope, and lack of clinical and laboratory data for making diagnosis of rhabdomyolysis.     

Other pathologic findings

Skin lesion

Four cases of dermatologic lesions are presented as sequalae of injection, i.e., one with fresh needle punctures, two cases with fresh punctures and sclerotic cutaneous veins (track mark),and one case with atrophic scars. Only one case whose endocarditis is a questionable consequence of fresh and previous lesions is found.  Others show no serious intravenous complications such as abscess, puffy hand, fasciitis, vein thrombosis and even septicemia. The minority of dermatologic lesion and complication may be explained by reasons as examples; 1. Some of them changes administration from intravenous route to intranasal or seldom oral route. The reasons for changing include concern about social stigmatas, preference for effective intranasal route, lack of additional paraphernalia, lower risk of drug dependence and sudden death. Avoidance of serious infections i.e., HIV and hepatitis is their considerable awareness as well. 2. Evidences of previous injection wound are uncommonly found in novice users especially when they sophisticatedly take great pains to conceal evidence of injection.

Angiitis

According to this study,there is one case of angiitis accidentally found in cerebrum in addition to pulmonary granuloma, cardiac ventricular hypertrophy, track marks and evidences of punctuate on both wrists. A polyarteritis-like syndrome in intravenous drug abuser was first described by Citron et al (1970).4) Since there is rarely case reported, having been reported cases are exclusively in amphetamine abusers and apparent declining in the number of case of necrotizing angiitis even among methamphetamine abusers. He suggests they may have been the result of some toxic contaminants mixed with heroin. As often as not, angiographic studies in heroin-abusing stroke victims will be normal. If any change is in evidence at all, it is likely to be spasm.4)

Body Packer Syndromes

                Leakage of ‘body packer’ was diagnosed in one case of 45-year-old Pakistani male decedent. Autopsy revealed mark edematous lungs and generalized congested organs including 5 poorly wrapped condoms in stomach and 2 leaky condoms in sigmoid colon. Each condom measuring 5 cm. in length and 3 cm. in width contain heroin powder. Heroin intoxication is confirmed by bile and urine examination.

            ‘Body packer syndrome’ first described as ingestion of balloons filled with cocaine by  Mebane s Devito in 1975,4) is early experienced in U.S. and often reported in Europe and North America, but this particular method of smuggling is becoming important means throughout the world.[21] Cocaine and heroin are nowadays popular drugs to conceal. Most of reported cases occurred in the destination country, where the markets were to be incidentally  found, as did this report. Departure point of this decedent is unknown. The packaging used in this case is not so sophisticated that leakage out of the condoms is prone to be. He does immediately not die after the onset of leakage due to insidious manner of only 2 leaky condoms that are distantly demonstrated near rectum. However, the constipation that is resulted from anticholinergic effect of heroin will lengthen transit time. So the time that absorption takes is enough for him to die.   

Reference

  1. Darke S. and Ross J. (2002) Suicide among heroin users: rates, risk factors and methods, Addiction, 97(1383-94).
  2. EMCDDA (2002) Mortality of drug users in the EU: coordination of implementation of new cohort studies, follow-up and analysis of existing cohorts and development of new methods and outputs. Project CT.OO.EP.13, European Monitoring Centre for Drugs and Drug Addiction, Lisbon.
  3. Ghuran A. and Nolan J. (2000) Recreational drug misuse.issues for the cardiologist. Heart,83 (627–33)
  4. Karch S. B. (2008) Karch’s pathology of drug abuse, 4th edn. Boca Raton: CRC Press.
  5. White J.and Irvine R. (1999) Mechanisms of fatal opioid overdose. Addiction,95(961–972).
  6. Bryant W.K., Galea S., Tracy M., Piper T.M., Tardiff K.J. and Vlahov D. (2003) Overdose deaths attributed to methadone and heroin in New York City,1990–98. Addiction,99 (846–54).
  7. Aderjan R.E. and Skopp G. (1998) Formation and clearance of active and inactive metabolites of opiates in humans, Ther Drug Monit,20,(561-569).
  8. Darke S., Kaye, S. and Duflou, J., 2006. Systemic disease among cases of fatal opioid toxicity. Addiction 101, (1299–1305).
  9. Darke S., Hall W., Weatherburn D. and Lind B. (1999) Fluctuations in heroin purity and the incidence of fatal heroin Overdose. Drug and Alcohol Dependence. 54, (155–161)
  10. Darke S. and Zador, D. (1996) Fatal heroin overdose: A review. Addiction 91(1757–1764).
  11. World Drug Report 2008. Opiates: Wholesale, street prices and purity levels (257 – 259).
  12. Ruttenber A.J., Kalter, H.O. and Santinga, P. (1990) The role of ethanol abuse in the etiology of heroin-related death. J. Forensic Sci. 35 (891–900).
  13. Levine B., Green D. and Smialek J.E. (1995) The role of ethanol in heroin deaths. J. Forensic Sci. 40,(808–810).
  14. Zador D., Sunjic S. and Darke S. (1996) Heroin-related deaths in New South Wales, 1992: Toxicological findings and  circumstances. Med. J. Aust. 164 (204–207).
  15. Sanchez J., Rodriguez B., De Al Fuente L., Barrio G., Vincente J., Roca, J., et al., (1995) Opiates or cocaine: mortality from acute reactions in six major Spanish cities. J. Epid. Pub. Health 49 (54–60).
  16. Phillip O., Robert F. and Jenny K. (2007) Does the combined use of heroin or methadone and other substances increase the risk of overdose? Drug related death Publications.
  17. Phillip O., Robert F. and Jenny K. (2007) Benzodiazepines and cocaine as risk factors in fatal opioid overdoses. rug related death Publications.
  18. White J.M. and Irvine R.J. (1999). Mechanisms of Fatal Opioid Overdose. Addiction, 94 (961-972).
  19. Hsu W.Y., Chiu Y.C. and Liao Y.C. (2009) Rhabdomyolysis and brain ischemic stroke in a heroin-dependent male under methadone maintenance therapy. Acta Psychiatr Scand, 120(76-81)
  20. Addingtion WW, Cugell DW and Bazley ES. (1972) The pulmonary edema of heroin toxicity-an example of the stiff lung syndrome. CHEST, 62(199-205).
  21. Leo P.J.,Sachter J.J. and Melrose M. (1995) Heroin bodypacking. J. Accid and Emer Med, 12(43-48).

งานพิษวิทยา

Promedical

คู่มือการเก็บตัวอย่างและส่งตรวจของกลุ่มงานพิษวิทยา [อ่านต่อ]

งานนิติพยาธิ

Promedical

ทำหน้าที่ชันสูตรพลิกศพ ณ สถานที่เกิดเหตุ  [บทความทั้งหมด]

งานตรวจเลือดชีวเคมีและเขม่าดินปืน

Promedical

คู่มือการเก็บและนำสิ่งส่งตรวจห้องปฏิบัติการของกลุ่มงาน...[อ่านต่อ]

งานพิสูจน์เอกลักษณ์บุคคล

ภาพถ่ายทางการแพทย์

Promedical

งานถ่ายภาพ เพื่อตรวจพิสูจน์ทราบทางนิติเวช และเพื่อเป็นหลักฐานในชั้นศาล โดยน้นความถูกต้องตามสรีระ [อ่านต่อ]

กลุ่มงานพิเศษ

Promedical

ทำหน้าที่ดูแลรักษาสถานที่พบศพและสภาพศพ เป็นศูนย์รวมข่าวและรับแจ้งเหตุ ประสานงานกำกับดูแลการเก็บศพ