J Forensic Sci, May 2015, Vol. 60, No. 3 doi: 10.1111/1556-4029.12706 Available online at: onlinelibrary.wiley.com
CASE REPORT PATHOLOGY/BIOLOGY; TOXICOLOGY
Sebastien Prat,1,2,3 M.D.; Guillaume Hoizey,3 Ph.D.; Thierry Lefrancq,4 M.D.; and Pauline Saint-Martin,5,6,7 M.D., Ph.D.
An Unusual Case of Strychnine Poisoning*
ABSTRACT: Strychnine-related death has been described since the 19th century. This alkaloid was discovered in 1818. Historically, strych-
nine was used by the South-East Asian autochthones on their arrows. However, its production was modified by legislation, which was used to protect people against accidental intoxications. Here, we present the case of a 69-year-old man who was found dead at home. During the autopsy, we found a blue substance in the stomach. Toxicological analysis measured strychnine at 0.29 lg/mL in the blood sample, which is a relatively low level in comparison with the results given in the literature. However, histologic examination and toxicological findings permitted the conclusion of strychnine poisoning.
KEYWORDS: forensic medicine, forensic pathology, strychnine, poisoning, Strychnos nux vomica, rodenticide Deaths linked to strychnine have been described in the literature since the 19th century. Strychnine is an alkaloid which was discovered in 1818 by two pharmacists, Dr Pelletier and Dr Caventou (1,2). It is obtained from various plants. The best known is Strychnos nux vomica, but it can also be found in Saint-Ignatius’ bean and snake-wood (Lignum colubrinum). These plants are found in South-East Asia, where natives have used the fruit to poison their arrow heads for years (1). It was first synthesized by Robert Woodward in 1954 (2). Its use has been regulated several times due to its high toxicity in various countries (3). For example, in France, in 1949, a ministerial order authorized the use of strychnine for the sole purpose of bait to destroy rodents, predatory birds, and small vermin. Its use was authorized for all periods of the year; however, a bright coloring agent must be added (4). In 1982, a new ministerial order was passed to modify the use of strychnine (5), which stipulated that it could only be used to kill moles. The bait could only be used by local authorities and under supervision. The bait had to be placed in the moles’ burrows, and public warning signs had to be put up. In 1999, a final ministerial order was passed, banning the use of strychnine completely (6). Since this definitive ban, deaths linked to strychnine have
1 Forensic Psychiatry Department, St Joseph’s Healthcare, Hamilton, ON, Canada. 2 Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada. 3 E.A. 2114 Psychologie des ^ages de la vie, Universite Francßois Rabelais de Tours, Tours, France. 4 Toxlab, Paris, France. 5 Centre de Pathologie, Nevers, France. 6 Institut Medico-legal, Centre Hospitalo-Universitaire de Tours, Tours, France. 7 Faculte de Medecine, Universite Francßois Rabelais de Tours, Tours, France. *Presented at the 65th Annual Meeting of the American Academy of Forensic Sciences, February 18–23, 2013, in Washington, DC. Received 5 Dec. 2013; accepted 29 April 2014.
816
become very rare. In cases where they do occur, the main question is to discover the origin of the product. Case Report We present the case of a 60-year-old man, who was found dead at home, lying on the sofa. We were not called to the scene. The investigators informed us that there was no evidence of any particular disorder. The photos we were given showed the body of a man on a sofa in supine position, with no remarkable features. On the coffee table, close to the sofa, there was a glass containing the remains of a bluish liquid. The circumstances of the discovery were unusual. The body was discovered by the police, who had come with bailiffs. There was a family dispute regarding inheritance, and the bailiffs had come to make an inventory of the goods claimed by the brothers of the deceased. The police had come because the deceased had told the bailiffs that he would be armed. We learned that a few hours before the body was discovered, the deceased had spoken to his sister on the phone and expressed his displeasure about the sheriff’s visit, but had not given any indication that he was suicidal. A note was found near the body, on which it was written, “This is a homicide – they have stolen everything from me.” External examination of the body did not reveal any traumatic injury or bruising indicating a violent attack or self-defense. We found no sign of intravenous injection. No other abnormalities were detected. The autopsy revealed nonspecific acute signs, in the form of blood stasis and pulmonary edema. Gastric contents were liquid, abundant, and blue in color. Gastric mucosa presented diffuse hemorrhagic stippling. Histopathological examination of major organs was normal, particularly kidneys and lungs. Toxicological analyses were carried out using gas chromatography with mass spectrometry, and liquid chromatography with diode array detection. Strychnine was found in the blood samples and gastric contents, with concentrations of 0.29 lg/mL and 12.2 lg/mL, respectively. The blue color suggested Taupicineâ, © 2015 American Academy of Forensic Sciences
PRAT ET AL.
a mole poison containing 10% strychnine with methylene blue added to avoid domestic accidents. Taken together, the evidence suggested death due to acute strychnine poisoning. When we had collated all of the results, we advised the investigators. The original container was not found. Discussion Strychnine poisoning is unusual, but frequently fatal without suitable early intervention. In a study of 73 cases of poisoning, 73% of the subjects suffered cardiorespiratory arrest before reaching hospital and died; 80% of these cases lived in rural areas (7). Accidental cases are rare. Poisoning is generally fatal without immediate treatment. The usual clinical signs are convulsions with normal consciousness and risus sardonicus after death (8). It has been described many times in the scientific literature since the nineteenth century. Strychnine poisoning is generally accidental in children and as a result of suicide in adults (9,10). The blue coloring of the product comes from methylene blue which is added to the preparation, as stipulated since the law of 1949, which made it compulsory to add a bright red, black, green, or blue coloring agent (4). Several cases have been described in the literature where poisoning occurred while taking cocaine, which is sometimes adulterated with strychnine (2,3,11–13). Most cases of poisoning are due to ingestion or inhalation. However, rare cases of poisoning by topical exposure have been reported (3). There are some historic and episodic cases of criminal strychnine poisoning. The most notable is the case of the serial killer Dr. Thomas Neill Cream, a Scottish doctor who lived in the second half of the 19th century, whose victims were women, particularly prostitutes, in Great Britain, Canada, and the USA. He used strychnine on several occasions. The story states that just before he was hung, he said that he was Jack the Ripper (14). There was also a case of mass poisoning in 1851 in Fort Jones, resulting in the death of nearly four thousand Indians (15). According to Makarovsky et al. (15), strychnine could be used for terrorist purposes. It is also said that strychnine was used at the beginning of the 20th century as a doping substance during the marathons of 1904 and 1908, when the runner was given an injection halfway through the race (16,17). This is because, in addition to its hyperexcitability action, strychnine also increases lung compliance (7,18). Different analytical methods have been developed to obtain rapid and reliable results. In 1899, Haw published a case in which strychnine was detected in organs 10 months after the body had been buried; however, there was no description of the method that was used (19). In 1960, strychnine was detected by coloration using Mandelin’s reagent (20). Since the 1970s, chromatography techniques using TLC and GC/NPD have been applied (20). More recently, GC/MS and HPLC techniques have been used (12,13,21). Techniques to extract the product have been developed to avoid the use of organic solvents (21). The blood concentration in our case was lower than that described in the literature. There is a published safe threshold serum concentration of 0.8 lg/mL, but this is contested; however, below this limit, the outcome of treatment is almost always successful (2,7,13). In our case, the blood dose was 0.29 lg/mL, which is well below the apparently safe serum concentration level. Rapid and appropriate treatment can ensure survival. As shown by our case, the circumstances of death are essential elements. Indeed, few people have access to this substance. In our case, the inquest
.
STRYCHNINE POISONING
817
returned a verdict of suicide based on the results of the toxicological analyses, even though the container was not found, a fact that we continue to find disturbing, in spite of the specific context. References 1. Simon J. Naming and toxicity: a history of strychnine. Stud Hist Philos Biol Biomed Sci 1999;30(4):505–25. 2. Philippe G, Angenot L, Tits M, Frederich M. About the toxicity of some Strychnos species and their alkaloids. Toxicon 2004;44(4):405–16. 3. Katz J, Prescott K, Woolf AD. Strychnine poisoning from a cambodian traditional remedy. Am J Emerg Med 1996;14(5):475–7. 4. Arr^ete du 15 juillet 1949 relatif a la condition de commerce et de l’emploi de la noix vomique, de la strychnine et de ses sels pour la destruction des animaux nuisibles. JOFR Juillet 1949;7275. 5. Arr^ete du 24 fevrier 1982 relatif a l’emploi de la strychnine et de ses sels en agriculture. JOFR Mar 10 1982;2549. 6. Arr^ete du 15 avril 1999 modifiant l’arr^ete du 26 avril 1988 relatif aux conditions generales de delivrance et d’emploi des preparations destiniees a la lutte contre les souris et les rats (rats noirs et surmulots) et abrogeant l’arr^ete du 24 fevrier 1982 concernant l’emploi de la strychnine en agriculture. JOFR mai 1999;7878. 7. Francßois B, Cailloce D, Marquet P, Billy V, Lachatre G, Dumont D, et al. Intoxication a la strychnine. Reanim. urgences 1996;5(4):395– 400. 8. Anderson CL. A case of strychnine poisoning. Can Med Assoc J 1935;33(3):307. 9. Starretz-Hacham O, Sofer S, Lifshitz M. Strychnine intoxication in a child. Isr Med Assoc J 2003;5(7):531–2. 10. Dasari S, Naha K. A rare case of strychnine poisoning by consumption of Strychnos nux-vomica leaves. Asian Pac J Trop Biomed 2011;1(2): S303–4. 11. Wijesekera ARL, Henry KD, Ranasinghe P. The detection and estimation of (A) arsenic in opium, and (B) strychnine in opium and heroin, as a means of identification of their respective sources. Forensic Sci Int 1988;36(3–4):193–209. 12. Duverneuil C, de la Grandmaison GL, de Mazancourt P, Alvarez J-C. Liquid chromatography/photodiode array detection for determination of strychnine in blood: a fatal case report. Forensic Sci Int 2004;141(1):17– 21. 13. Van Eenoo P, Deventer K, Roels K, Delbeke FT. Quantitative LC–MS determination of strychnine in urine after ingestion of a Strychnos nuxvomica preparation and its consequences in doping control. Forensic Sci Int 2006;164(2–3):159–63. 14. McLaren A. A prescription for murder: the Victorian serial killings of Dr. Thomas Neill Cream. Chicago, IL: University of Chicago Press, 1995. 15. Makarovsky I, Markel G, Hoffman A, Schein O, Brosh-Nissimov T, Tashma Z, et al. Strychnine – a killer from the past. Isr Med Assoc J 2008;10(2):142–5. 16. Polley M. From Windsor Castle to White City: the 1908 Olympic marathon route. Lond J 2009;34(2):163–78. 17. Hoberman J. History and prevalence of doping in the marathon. Sports Med 2007;37(4):386–8. 18. Ethyl strychnine as a respiratory stimulant. Lancet 1937;229(5930):1000. 19. Haw W. Strycnine poisoning and its detection in exhumed bodies. Lancet 1899;154(3969):835–7. 20. Marques EP, Gil F, Proencßa P, Monsanto P, Oliveira MF, Castanheira A, et al. Analytical method for the determination of strychnine in tissues by gas chromatography/mass spectrometry: two case reports. Forensic Sci Int 2000;110(2):145–52. 21. Barroso M, Gallardo E, Margalho C, Avila S, Marques EP, Vieira DN, et al. Application of solid phase microextraction to the determination of strychnine in blood. J Chromatogr B 2005;816(1–2):29–34. Additional information and reprints requests: Sebastien Prat, M.D. Forensic Psychiatry Department St Joseph’s Healthcare Centre for Mountain Health Services 100 West 5th Street Hamilton, ON L8N 3K7, Canada E-mail: [email protected]
Copyright of Journal of Forensic Sciences (Wiley-Blackwell) is the property of WileyBlackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
CASE REPORT PATHOLOGY/BIOLOGY; TOXICOLOGY
Sebastien Prat,1,2,3 M.D.; Guillaume Hoizey,3 Ph.D.; Thierry Lefrancq,4 M.D.; and Pauline Saint-Martin,5,6,7 M.D., Ph.D.
An Unusual Case of Strychnine Poisoning*
ABSTRACT: Strychnine-related death has been described since the 19th century. This alkaloid was discovered in 1818. Historically, strych-
nine was used by the South-East Asian autochthones on their arrows. However, its production was modified by legislation, which was used to protect people against accidental intoxications. Here, we present the case of a 69-year-old man who was found dead at home. During the autopsy, we found a blue substance in the stomach. Toxicological analysis measured strychnine at 0.29 lg/mL in the blood sample, which is a relatively low level in comparison with the results given in the literature. However, histologic examination and toxicological findings permitted the conclusion of strychnine poisoning.
KEYWORDS: forensic medicine, forensic pathology, strychnine, poisoning, Strychnos nux vomica, rodenticide Deaths linked to strychnine have been described in the literature since the 19th century. Strychnine is an alkaloid which was discovered in 1818 by two pharmacists, Dr Pelletier and Dr Caventou (1,2). It is obtained from various plants. The best known is Strychnos nux vomica, but it can also be found in Saint-Ignatius’ bean and snake-wood (Lignum colubrinum). These plants are found in South-East Asia, where natives have used the fruit to poison their arrow heads for years (1). It was first synthesized by Robert Woodward in 1954 (2). Its use has been regulated several times due to its high toxicity in various countries (3). For example, in France, in 1949, a ministerial order authorized the use of strychnine for the sole purpose of bait to destroy rodents, predatory birds, and small vermin. Its use was authorized for all periods of the year; however, a bright coloring agent must be added (4). In 1982, a new ministerial order was passed to modify the use of strychnine (5), which stipulated that it could only be used to kill moles. The bait could only be used by local authorities and under supervision. The bait had to be placed in the moles’ burrows, and public warning signs had to be put up. In 1999, a final ministerial order was passed, banning the use of strychnine completely (6). Since this definitive ban, deaths linked to strychnine have
1 Forensic Psychiatry Department, St Joseph’s Healthcare, Hamilton, ON, Canada. 2 Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada. 3 E.A. 2114 Psychologie des ^ages de la vie, Universite Francßois Rabelais de Tours, Tours, France. 4 Toxlab, Paris, France. 5 Centre de Pathologie, Nevers, France. 6 Institut Medico-legal, Centre Hospitalo-Universitaire de Tours, Tours, France. 7 Faculte de Medecine, Universite Francßois Rabelais de Tours, Tours, France. *Presented at the 65th Annual Meeting of the American Academy of Forensic Sciences, February 18–23, 2013, in Washington, DC. Received 5 Dec. 2013; accepted 29 April 2014.
816
become very rare. In cases where they do occur, the main question is to discover the origin of the product. Case Report We present the case of a 60-year-old man, who was found dead at home, lying on the sofa. We were not called to the scene. The investigators informed us that there was no evidence of any particular disorder. The photos we were given showed the body of a man on a sofa in supine position, with no remarkable features. On the coffee table, close to the sofa, there was a glass containing the remains of a bluish liquid. The circumstances of the discovery were unusual. The body was discovered by the police, who had come with bailiffs. There was a family dispute regarding inheritance, and the bailiffs had come to make an inventory of the goods claimed by the brothers of the deceased. The police had come because the deceased had told the bailiffs that he would be armed. We learned that a few hours before the body was discovered, the deceased had spoken to his sister on the phone and expressed his displeasure about the sheriff’s visit, but had not given any indication that he was suicidal. A note was found near the body, on which it was written, “This is a homicide – they have stolen everything from me.” External examination of the body did not reveal any traumatic injury or bruising indicating a violent attack or self-defense. We found no sign of intravenous injection. No other abnormalities were detected. The autopsy revealed nonspecific acute signs, in the form of blood stasis and pulmonary edema. Gastric contents were liquid, abundant, and blue in color. Gastric mucosa presented diffuse hemorrhagic stippling. Histopathological examination of major organs was normal, particularly kidneys and lungs. Toxicological analyses were carried out using gas chromatography with mass spectrometry, and liquid chromatography with diode array detection. Strychnine was found in the blood samples and gastric contents, with concentrations of 0.29 lg/mL and 12.2 lg/mL, respectively. The blue color suggested Taupicineâ, © 2015 American Academy of Forensic Sciences
PRAT ET AL.
a mole poison containing 10% strychnine with methylene blue added to avoid domestic accidents. Taken together, the evidence suggested death due to acute strychnine poisoning. When we had collated all of the results, we advised the investigators. The original container was not found. Discussion Strychnine poisoning is unusual, but frequently fatal without suitable early intervention. In a study of 73 cases of poisoning, 73% of the subjects suffered cardiorespiratory arrest before reaching hospital and died; 80% of these cases lived in rural areas (7). Accidental cases are rare. Poisoning is generally fatal without immediate treatment. The usual clinical signs are convulsions with normal consciousness and risus sardonicus after death (8). It has been described many times in the scientific literature since the nineteenth century. Strychnine poisoning is generally accidental in children and as a result of suicide in adults (9,10). The blue coloring of the product comes from methylene blue which is added to the preparation, as stipulated since the law of 1949, which made it compulsory to add a bright red, black, green, or blue coloring agent (4). Several cases have been described in the literature where poisoning occurred while taking cocaine, which is sometimes adulterated with strychnine (2,3,11–13). Most cases of poisoning are due to ingestion or inhalation. However, rare cases of poisoning by topical exposure have been reported (3). There are some historic and episodic cases of criminal strychnine poisoning. The most notable is the case of the serial killer Dr. Thomas Neill Cream, a Scottish doctor who lived in the second half of the 19th century, whose victims were women, particularly prostitutes, in Great Britain, Canada, and the USA. He used strychnine on several occasions. The story states that just before he was hung, he said that he was Jack the Ripper (14). There was also a case of mass poisoning in 1851 in Fort Jones, resulting in the death of nearly four thousand Indians (15). According to Makarovsky et al. (15), strychnine could be used for terrorist purposes. It is also said that strychnine was used at the beginning of the 20th century as a doping substance during the marathons of 1904 and 1908, when the runner was given an injection halfway through the race (16,17). This is because, in addition to its hyperexcitability action, strychnine also increases lung compliance (7,18). Different analytical methods have been developed to obtain rapid and reliable results. In 1899, Haw published a case in which strychnine was detected in organs 10 months after the body had been buried; however, there was no description of the method that was used (19). In 1960, strychnine was detected by coloration using Mandelin’s reagent (20). Since the 1970s, chromatography techniques using TLC and GC/NPD have been applied (20). More recently, GC/MS and HPLC techniques have been used (12,13,21). Techniques to extract the product have been developed to avoid the use of organic solvents (21). The blood concentration in our case was lower than that described in the literature. There is a published safe threshold serum concentration of 0.8 lg/mL, but this is contested; however, below this limit, the outcome of treatment is almost always successful (2,7,13). In our case, the blood dose was 0.29 lg/mL, which is well below the apparently safe serum concentration level. Rapid and appropriate treatment can ensure survival. As shown by our case, the circumstances of death are essential elements. Indeed, few people have access to this substance. In our case, the inquest
.
STRYCHNINE POISONING
817
returned a verdict of suicide based on the results of the toxicological analyses, even though the container was not found, a fact that we continue to find disturbing, in spite of the specific context. References 1. Simon J. Naming and toxicity: a history of strychnine. Stud Hist Philos Biol Biomed Sci 1999;30(4):505–25. 2. Philippe G, Angenot L, Tits M, Frederich M. About the toxicity of some Strychnos species and their alkaloids. Toxicon 2004;44(4):405–16. 3. Katz J, Prescott K, Woolf AD. Strychnine poisoning from a cambodian traditional remedy. Am J Emerg Med 1996;14(5):475–7. 4. Arr^ete du 15 juillet 1949 relatif a la condition de commerce et de l’emploi de la noix vomique, de la strychnine et de ses sels pour la destruction des animaux nuisibles. JOFR Juillet 1949;7275. 5. Arr^ete du 24 fevrier 1982 relatif a l’emploi de la strychnine et de ses sels en agriculture. JOFR Mar 10 1982;2549. 6. Arr^ete du 15 avril 1999 modifiant l’arr^ete du 26 avril 1988 relatif aux conditions generales de delivrance et d’emploi des preparations destiniees a la lutte contre les souris et les rats (rats noirs et surmulots) et abrogeant l’arr^ete du 24 fevrier 1982 concernant l’emploi de la strychnine en agriculture. JOFR mai 1999;7878. 7. Francßois B, Cailloce D, Marquet P, Billy V, Lachatre G, Dumont D, et al. Intoxication a la strychnine. Reanim. urgences 1996;5(4):395– 400. 8. Anderson CL. A case of strychnine poisoning. Can Med Assoc J 1935;33(3):307. 9. Starretz-Hacham O, Sofer S, Lifshitz M. Strychnine intoxication in a child. Isr Med Assoc J 2003;5(7):531–2. 10. Dasari S, Naha K. A rare case of strychnine poisoning by consumption of Strychnos nux-vomica leaves. Asian Pac J Trop Biomed 2011;1(2): S303–4. 11. Wijesekera ARL, Henry KD, Ranasinghe P. The detection and estimation of (A) arsenic in opium, and (B) strychnine in opium and heroin, as a means of identification of their respective sources. Forensic Sci Int 1988;36(3–4):193–209. 12. Duverneuil C, de la Grandmaison GL, de Mazancourt P, Alvarez J-C. Liquid chromatography/photodiode array detection for determination of strychnine in blood: a fatal case report. Forensic Sci Int 2004;141(1):17– 21. 13. Van Eenoo P, Deventer K, Roels K, Delbeke FT. Quantitative LC–MS determination of strychnine in urine after ingestion of a Strychnos nuxvomica preparation and its consequences in doping control. Forensic Sci Int 2006;164(2–3):159–63. 14. McLaren A. A prescription for murder: the Victorian serial killings of Dr. Thomas Neill Cream. Chicago, IL: University of Chicago Press, 1995. 15. Makarovsky I, Markel G, Hoffman A, Schein O, Brosh-Nissimov T, Tashma Z, et al. Strychnine – a killer from the past. Isr Med Assoc J 2008;10(2):142–5. 16. Polley M. From Windsor Castle to White City: the 1908 Olympic marathon route. Lond J 2009;34(2):163–78. 17. Hoberman J. History and prevalence of doping in the marathon. Sports Med 2007;37(4):386–8. 18. Ethyl strychnine as a respiratory stimulant. Lancet 1937;229(5930):1000. 19. Haw W. Strycnine poisoning and its detection in exhumed bodies. Lancet 1899;154(3969):835–7. 20. Marques EP, Gil F, Proencßa P, Monsanto P, Oliveira MF, Castanheira A, et al. Analytical method for the determination of strychnine in tissues by gas chromatography/mass spectrometry: two case reports. Forensic Sci Int 2000;110(2):145–52. 21. Barroso M, Gallardo E, Margalho C, Avila S, Marques EP, Vieira DN, et al. Application of solid phase microextraction to the determination of strychnine in blood. J Chromatogr B 2005;816(1–2):29–34. Additional information and reprints requests: Sebastien Prat, M.D. Forensic Psychiatry Department St Joseph’s Healthcare Centre for Mountain Health Services 100 West 5th Street Hamilton, ON L8N 3K7, Canada E-mail: [email protected]
Copyright of Journal of Forensic Sciences (Wiley-Blackwell) is the property of WileyBlackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
