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Fatal methadone intoxication in an infant
Forensic Science International 153 (2005) 71–73 www.elsevier.com/locate/forsciint
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Fatal methadone intoxication in an infant Fiona J. Couper *, Kiran Chopra, Marie Lydie Y. Pierre-Louis Office of the Chief Medical Examiner, 1910 Massachusetts Avenue SE, Building 27, Washington, DC 20003, USA Available online 6 June 2005
Abstract Presented are the case history and toxicological findings of an infant fatality involving methadone. A mother found her 10month-old infant unresponsive in a crib. The infant was taken to a hospital; however, she was cold and stiff on arrival and was pronounced dead. Few details regarding the case history were known at the time, and the autopsy findings were unremarkable. Specimens were submitted for a full toxicological analysis, including an alcohol analysis by headspace gas chromatography with flame ionization detection; a screen for drugs of abuse and several prescription drug classes using an enzyme-linked immunosorbent assay technique (ELISA); and a screen for basic compounds using gas chromatography–mass spectrometry (GC–MS). Positive findings were confirmed and quantitated using GC–MS. Methadone was detected in subclavian blood at a concentration of 0.67 mg/L. The cause of death was determined to be ‘‘methadone intoxication’’, and the manner of death was ‘‘homicide’’. A discussion of the case circumstances, the toxicology findings and methadone pharmacokinetics are presented. # 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Methadone; Infant; Fatality
1. Introduction Methadone is a synthetic narcotic analgesic prescribed for the relief of moderate-to-severe pain. It is also used in the detoxification treatment of opiate dependence, and for maintenance in heroin and narcotic addiction. Recreationally, methadone is abused for its sedative and analgesic effects. Methadone hydrochloride is a schedule II controlled substance available by prescription as an oral solution (1–2 mg/ mL strength), tablets (5–10 mg), dispersible tablets (40 mg) and injectable solutions (10 mg/mL). For the relief of severe acute pain, a typical adult dose is 2.5–10 mg every 3–4 h. For methadone maintenance, the daily dose is generally 60–80 mg, but can vary from 30 to 120 mg.
* Corresponding author. Tel.: +1 202 698 9000; fax: +1 202 698 9104. E-mail address: [email protected] (F.J. Couper).
Methadone is a long acting m opioid receptor agonist with potent central analgesic, sedative and antitussive actions. Methadone inhibits ascending pain pathways, alters perception of and response to pain (dissociative effect) and produces general CNS depression. Respiratory depression also occurs due to complete blockage of respiratory centers to pCO2. The onset of analgesia and other effects occurs 30–60 min after oral administration. Following a single oral dose, effects may last up to 6–8 h; increasing to 22–48 h in cases of chronic administration. The half-life of (R,S)methadone is 15–60 h. The primary effects of methadone include drowsiness, sedation, dizziness, mood swings (euphoria to dysphoria), depressed reflexes, altered sensory perception, stupor and coma. Other physiological effects include strong analgesia, headache, dry mouth, facial flushing, sweating, nausea and vomiting, respiratory depression, muscle flaccidity, pupil constriction (miosis) and decreased heart rate. Sleep disorders and concentration disorders may also occur. Signs and
0379-0738/$ – see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.forsciint.2005.04.014
72
F.J. Couper et al. / Forensic Science International 153 (2005) 71–73
symptoms of overdose may include slow and shallow breathing, clammy skin, convulsions, extreme somnolence, respiratory depression, apnea, circulatory collapse, cardiac arrest, coma and possible death. Upon repeated administration, tolerance may develop to the nauseant, miotic, sedative, respiratory depressant and cardiovascular effects of methadone. Withdrawal symptoms are similar to those of other opioids but are less severe, slower in onset and last longer. Symptoms include watery eyes, runny nose, nausea, loss of appetite, diarrhea, cramps, muscle aches, dysphoria, restlessness, irritability, anxiety, tremors, chills, increased sensitivity to pain, insomnia and tachycardia. Fatal and non-fatal accidental methadone intoxications in children have been previously reported, as have cases of fatal intoxications when methadone doses have commenced or have been increased suddenly during maintenance therapy [1–5]. In this report, we detail the deliberate and continual administration of methadone to an infant for the purpose of sedation, eventually resulting in the infant’s death.
2. Methods Specimens taken during a routine autopsy included subclavian blood, vitreous, liver, brain and gastric contents, and were stored refrigerated (4 8C) until use. Subclavian blood underwent an alcohol analysis for ethanol, methanol, acetone and isopropanol by headspace gas chromatography with flame ionization detection. Extracts of subclavian blood underwent a screen for drugs of abuse and several prescription drug classes using an enzyme-linked immunosorbent assay (ELISA) technique, which screened for the following substances: amphetamines (cut-off limit 50 ng/mL), barbiturates (50 ng/mL), benzodiazepines (100 ng/mL), cannabinoids (25 ng/mL), cocaine metabolites (40 ng/mL), methamphetamines (50 ng/mL), methadone (25 ng/mL), opiates (25 ng/ mL), phencyclidine (10 ng/mL) and propoxyphene (50 ng/ mL). Additionally, an n-butylchloride extract of selected specimens underwent a screen for basic compounds using gas chromatography–mass spectrometry (GC–MS). Positive findings were confirmed and quantitated using GC–MS.
3. Results The post-mortem examination was unremarkable, although congestion of internal organs was noted. Methadone was detected in subclavian blood at a concentration of 0.67 mg/L. Concentrations of methadone in other postmortem fluids and tissues are shown in Table 1.
4. Discussion At 10-months of age, the infant had been a healthy 19 lb baby girl who had recent cold symptoms of coughing and
Table 1 Methadone concentrations in the post-mortem fluids and tissues of a 10-month-old infant Specimen
Methadone concentration
Subclavian blood Vitreous Liver Brain
0.67 mg/L 0.24 mg/L 1.83 mg/kg 0.95 mg/kg
wheezing and a possible previous medical history of asthma. Her pediatrician had last seen her 3 weeks prior to death during a regular scheduled visit. The infant was found unresponsive in her crib at approximately 7:00 a.m., having last been seen alive at 23:00 h, the previous night. The infant was last fed between 19:00 and 20:00 h that evening. When paramedics arrived in the morning, they found the infant cold and stiff, and her pupils non-reactive. The infant was taken to a hospital where she was observed to be cyanotic, in asystole, with lividity present on her face. Vomitus was also observed in her mouth. Few details regarding the case history were known at the time, and the post-mortem examination was unremarkable. The unexpected blood methadone result (0.67 mg/L), in an otherwise healthy infant, immediately initiated a thorough forensic investigation. The infant had been born fullterm (7 lbs, 14 oz); however, she had remained in the hospital for a period of 1 month while being weaned off methadone. The mother had been a heroin addict for over 20 years and had been on a methadone maintenance program throughout her pregnancy. The mother had regularly been given ‘‘take home’’ methadone doses from the methadone clinic she attended. Her other child, now a 2-year-old boy, had also been weaned off methadone following his birth. The police had not observed any methadone bottles at the infant’s house, nor had the mother mentioned finding medication bottles of any sort near the child. Since it was thought unlikely at the time that the infant had accidentally taken the methadone herself, the police sought to question the mother further. The mother admitted to the following details: for several months after the infant’s discharge from the hospital, the mother was coping with caring for her daughter. Increasingly, the mother grew more tired and was managing less with the infant’s crying. On one particular day, she took the infant to a relative’s house for a break. When the infant starting ‘‘fussing’’ again, the mother’s relative suggested dipping a finger into the liquid methadone and then placing the finger in the child’s mouth. This had the desired effect at the time of calming the infant down. Several weeks later, the mother again administered liquid methadone to the infant to stop the child from ‘‘crying and fussing’’. Soon afterwards, the mother started to administer the methadone semi-regularly to sedate the child. For example, she would medicate the child with some methadone before going shopping. This soon began to occur ‘‘one or
F.J. Couper et al. / Forensic Science International 153 (2005) 71–73
two times a week’’. The mother began using a medicine dropper to administer the drug but ‘‘never went over the first line’’. She would either add the methadone to the infant’s formula and feed the child over a period of time, or directly administer the methadone to the infant via the dropper. This occurred for several months leading up to the infant’s death. At the time, the mother did not think what she was doing was wrong and found it was just a way to cope. On the day of the infant’s death, the mother admitted to administering approximately twice the amount of methadone she normally gave her child – up to the second line on the dropper. She stated she had never previously given her child that amount. The infant was found unresponsive in her crib the next morning. The aforementioned circumstances appear to correspond to the pharmacology of methadone. Every time the infant was administered methadone, the drug’s ‘‘sedating’’ effects lasted approximately 48 h. The child would have then experienced methadone withdrawal symptoms, which would appear to the mother as ‘‘fussing’’ and irritability. The mother stated that the ‘‘crying noise’’ her infant made at times was unbearable. This would subsequently prompt the mother to administer another dose of methadone to sedate the child and stop her from crying; and the cycle would begin again.
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5. Conclusion The cause of death was determined to be ‘‘methadone intoxication’’, and the manner of death was ‘‘homicide’’. The infant’s mother was charged with felony murder. She pleaded guilty and is serving a 10-year sentence.
References [1] A. Leblanc, N. Benbrick, M.H. Moreau, Methadone poisoning in a 1-year-old child treated by continuous infusion of naloxone, Arch. Pediatr. 9 (2002) 694–696. [2] L. Li, B. Levine, J.E. Smialek, Fatal methadone poisoning in children: Maryland 1992–1996, Subst. Use Misuse 35 (2000) 1141–1148. [3] A. Lalkin, B.M. Kapur, Z.H. Verjee, G. Koren, Contamination of antibiotics resulting in severe pediatric methadone poisoning, Ann. Pharmacother. 33 (1999) 314–317. [4] J.M. Binchy, E.M. Molyneux, J. Manning, Accidental ingestion of methadone by children in Merseyside, BMJ 308 (1994) 1335–1336. [5] S. Blatman, Narcotic poisoning of children (1) through accidental ingestion of methadone and (2) in utero, Pediatrics 54 (1974) 329–332.
Short communication
Fatal methadone intoxication in an infant Fiona J. Couper *, Kiran Chopra, Marie Lydie Y. Pierre-Louis Office of the Chief Medical Examiner, 1910 Massachusetts Avenue SE, Building 27, Washington, DC 20003, USA Available online 6 June 2005
Abstract Presented are the case history and toxicological findings of an infant fatality involving methadone. A mother found her 10month-old infant unresponsive in a crib. The infant was taken to a hospital; however, she was cold and stiff on arrival and was pronounced dead. Few details regarding the case history were known at the time, and the autopsy findings were unremarkable. Specimens were submitted for a full toxicological analysis, including an alcohol analysis by headspace gas chromatography with flame ionization detection; a screen for drugs of abuse and several prescription drug classes using an enzyme-linked immunosorbent assay technique (ELISA); and a screen for basic compounds using gas chromatography–mass spectrometry (GC–MS). Positive findings were confirmed and quantitated using GC–MS. Methadone was detected in subclavian blood at a concentration of 0.67 mg/L. The cause of death was determined to be ‘‘methadone intoxication’’, and the manner of death was ‘‘homicide’’. A discussion of the case circumstances, the toxicology findings and methadone pharmacokinetics are presented. # 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Methadone; Infant; Fatality
1. Introduction Methadone is a synthetic narcotic analgesic prescribed for the relief of moderate-to-severe pain. It is also used in the detoxification treatment of opiate dependence, and for maintenance in heroin and narcotic addiction. Recreationally, methadone is abused for its sedative and analgesic effects. Methadone hydrochloride is a schedule II controlled substance available by prescription as an oral solution (1–2 mg/ mL strength), tablets (5–10 mg), dispersible tablets (40 mg) and injectable solutions (10 mg/mL). For the relief of severe acute pain, a typical adult dose is 2.5–10 mg every 3–4 h. For methadone maintenance, the daily dose is generally 60–80 mg, but can vary from 30 to 120 mg.
* Corresponding author. Tel.: +1 202 698 9000; fax: +1 202 698 9104. E-mail address: [email protected] (F.J. Couper).
Methadone is a long acting m opioid receptor agonist with potent central analgesic, sedative and antitussive actions. Methadone inhibits ascending pain pathways, alters perception of and response to pain (dissociative effect) and produces general CNS depression. Respiratory depression also occurs due to complete blockage of respiratory centers to pCO2. The onset of analgesia and other effects occurs 30–60 min after oral administration. Following a single oral dose, effects may last up to 6–8 h; increasing to 22–48 h in cases of chronic administration. The half-life of (R,S)methadone is 15–60 h. The primary effects of methadone include drowsiness, sedation, dizziness, mood swings (euphoria to dysphoria), depressed reflexes, altered sensory perception, stupor and coma. Other physiological effects include strong analgesia, headache, dry mouth, facial flushing, sweating, nausea and vomiting, respiratory depression, muscle flaccidity, pupil constriction (miosis) and decreased heart rate. Sleep disorders and concentration disorders may also occur. Signs and
0379-0738/$ – see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.forsciint.2005.04.014
72
F.J. Couper et al. / Forensic Science International 153 (2005) 71–73
symptoms of overdose may include slow and shallow breathing, clammy skin, convulsions, extreme somnolence, respiratory depression, apnea, circulatory collapse, cardiac arrest, coma and possible death. Upon repeated administration, tolerance may develop to the nauseant, miotic, sedative, respiratory depressant and cardiovascular effects of methadone. Withdrawal symptoms are similar to those of other opioids but are less severe, slower in onset and last longer. Symptoms include watery eyes, runny nose, nausea, loss of appetite, diarrhea, cramps, muscle aches, dysphoria, restlessness, irritability, anxiety, tremors, chills, increased sensitivity to pain, insomnia and tachycardia. Fatal and non-fatal accidental methadone intoxications in children have been previously reported, as have cases of fatal intoxications when methadone doses have commenced or have been increased suddenly during maintenance therapy [1–5]. In this report, we detail the deliberate and continual administration of methadone to an infant for the purpose of sedation, eventually resulting in the infant’s death.
2. Methods Specimens taken during a routine autopsy included subclavian blood, vitreous, liver, brain and gastric contents, and were stored refrigerated (4 8C) until use. Subclavian blood underwent an alcohol analysis for ethanol, methanol, acetone and isopropanol by headspace gas chromatography with flame ionization detection. Extracts of subclavian blood underwent a screen for drugs of abuse and several prescription drug classes using an enzyme-linked immunosorbent assay (ELISA) technique, which screened for the following substances: amphetamines (cut-off limit 50 ng/mL), barbiturates (50 ng/mL), benzodiazepines (100 ng/mL), cannabinoids (25 ng/mL), cocaine metabolites (40 ng/mL), methamphetamines (50 ng/mL), methadone (25 ng/mL), opiates (25 ng/ mL), phencyclidine (10 ng/mL) and propoxyphene (50 ng/ mL). Additionally, an n-butylchloride extract of selected specimens underwent a screen for basic compounds using gas chromatography–mass spectrometry (GC–MS). Positive findings were confirmed and quantitated using GC–MS.
3. Results The post-mortem examination was unremarkable, although congestion of internal organs was noted. Methadone was detected in subclavian blood at a concentration of 0.67 mg/L. Concentrations of methadone in other postmortem fluids and tissues are shown in Table 1.
4. Discussion At 10-months of age, the infant had been a healthy 19 lb baby girl who had recent cold symptoms of coughing and
Table 1 Methadone concentrations in the post-mortem fluids and tissues of a 10-month-old infant Specimen
Methadone concentration
Subclavian blood Vitreous Liver Brain
0.67 mg/L 0.24 mg/L 1.83 mg/kg 0.95 mg/kg
wheezing and a possible previous medical history of asthma. Her pediatrician had last seen her 3 weeks prior to death during a regular scheduled visit. The infant was found unresponsive in her crib at approximately 7:00 a.m., having last been seen alive at 23:00 h, the previous night. The infant was last fed between 19:00 and 20:00 h that evening. When paramedics arrived in the morning, they found the infant cold and stiff, and her pupils non-reactive. The infant was taken to a hospital where she was observed to be cyanotic, in asystole, with lividity present on her face. Vomitus was also observed in her mouth. Few details regarding the case history were known at the time, and the post-mortem examination was unremarkable. The unexpected blood methadone result (0.67 mg/L), in an otherwise healthy infant, immediately initiated a thorough forensic investigation. The infant had been born fullterm (7 lbs, 14 oz); however, she had remained in the hospital for a period of 1 month while being weaned off methadone. The mother had been a heroin addict for over 20 years and had been on a methadone maintenance program throughout her pregnancy. The mother had regularly been given ‘‘take home’’ methadone doses from the methadone clinic she attended. Her other child, now a 2-year-old boy, had also been weaned off methadone following his birth. The police had not observed any methadone bottles at the infant’s house, nor had the mother mentioned finding medication bottles of any sort near the child. Since it was thought unlikely at the time that the infant had accidentally taken the methadone herself, the police sought to question the mother further. The mother admitted to the following details: for several months after the infant’s discharge from the hospital, the mother was coping with caring for her daughter. Increasingly, the mother grew more tired and was managing less with the infant’s crying. On one particular day, she took the infant to a relative’s house for a break. When the infant starting ‘‘fussing’’ again, the mother’s relative suggested dipping a finger into the liquid methadone and then placing the finger in the child’s mouth. This had the desired effect at the time of calming the infant down. Several weeks later, the mother again administered liquid methadone to the infant to stop the child from ‘‘crying and fussing’’. Soon afterwards, the mother started to administer the methadone semi-regularly to sedate the child. For example, she would medicate the child with some methadone before going shopping. This soon began to occur ‘‘one or
F.J. Couper et al. / Forensic Science International 153 (2005) 71–73
two times a week’’. The mother began using a medicine dropper to administer the drug but ‘‘never went over the first line’’. She would either add the methadone to the infant’s formula and feed the child over a period of time, or directly administer the methadone to the infant via the dropper. This occurred for several months leading up to the infant’s death. At the time, the mother did not think what she was doing was wrong and found it was just a way to cope. On the day of the infant’s death, the mother admitted to administering approximately twice the amount of methadone she normally gave her child – up to the second line on the dropper. She stated she had never previously given her child that amount. The infant was found unresponsive in her crib the next morning. The aforementioned circumstances appear to correspond to the pharmacology of methadone. Every time the infant was administered methadone, the drug’s ‘‘sedating’’ effects lasted approximately 48 h. The child would have then experienced methadone withdrawal symptoms, which would appear to the mother as ‘‘fussing’’ and irritability. The mother stated that the ‘‘crying noise’’ her infant made at times was unbearable. This would subsequently prompt the mother to administer another dose of methadone to sedate the child and stop her from crying; and the cycle would begin again.
73
5. Conclusion The cause of death was determined to be ‘‘methadone intoxication’’, and the manner of death was ‘‘homicide’’. The infant’s mother was charged with felony murder. She pleaded guilty and is serving a 10-year sentence.
References [1] A. Leblanc, N. Benbrick, M.H. Moreau, Methadone poisoning in a 1-year-old child treated by continuous infusion of naloxone, Arch. Pediatr. 9 (2002) 694–696. [2] L. Li, B. Levine, J.E. Smialek, Fatal methadone poisoning in children: Maryland 1992–1996, Subst. Use Misuse 35 (2000) 1141–1148. [3] A. Lalkin, B.M. Kapur, Z.H. Verjee, G. Koren, Contamination of antibiotics resulting in severe pediatric methadone poisoning, Ann. Pharmacother. 33 (1999) 314–317. [4] J.M. Binchy, E.M. Molyneux, J. Manning, Accidental ingestion of methadone by children in Merseyside, BMJ 308 (1994) 1335–1336. [5] S. Blatman, Narcotic poisoning of children (1) through accidental ingestion of methadone and (2) in utero, Pediatrics 54 (1974) 329–332.