from the journal of Forensic Toxicology, 2018:
Dear Editor
We recently had a case with interesting toxicology results that we felt merited publication in the literature to bring attention to what could become a trend. While a similar case has been published recently [1], ours presented some unique learning points not otherwise covered.
The decedent was a 37-year-old white male, who was found unresponsive in his locked apartment in a moderate state of decomposition with skin discoloration, bloating, bullae formation, and skin slippage. He was seated and leaning over the back of a chair at a desk. The desk had a handwritten last will and testament and a bottle which contained a clear liquid. Autopsy did not reveal any signs of trauma, foul play, or obvious cause of death. Toxicology was sent; however, due to the state of decomposition, only liver, spleen, and cavity fluid were able to be sent to NMS Labs. The liver was positive for pentobarbital (190 µg/g) and metoclopramide (which could not be quantitated due to sample matrix issues); the spleen was positive for both pentobarbital (170 µg/g) and metoclopramide (56 μg/g). Directed analysis of the cavity fluid revealed a pentobarbital concentration of 670 µg/mL. Metoclopramide was detected in the cavity fluid as well, but there was insufficient sample for quantitation. The liquid found within the bottle by the decedent had evaporated in the postmortem interval, and was unable to be tested. A conversation with the family of the decedent revealed that he had often talked about suicide, but there were no known previous attempts. This case was ultimately signed out as pentobarbital toxicity, with suicide as the manner of death.
Pentobarbital belongs to the barbiturate class of medications and works via the GABA-A receptor to hyperpolarize neurons and cause generalized central nervous system depression. Barbiturates do this by acting as an agonist and are capable of directly opening the GABA-A receptor, keeping it open for a longer time. This is in contrast to benzodiazepines, which, while they work on the same receptor, have a different binding site and are unable to directly open the channel. Rather, they increase the potential for the channel to be opened by GABA. Having an effective antidote, fewer side effects, and more forgiving withdrawal are all reasons why benzodiazepines are preferred today [2]. Barbiturates in general are rarely used in the United States, although some indications, such as second or third line therapies for seizures or migraines still exist. Pentobarbital is used almost exclusively in this country for euthanizing animals, raising the concern that most people who commit suicide using it are in veterinary medicine [3].
Lethal levels for pentobarbital are considered to be about ten times the usual oral dose. Potential lethal blood concentrations are those in excess of 80 µg/mL [4]. Metoclopramide is an antiemetic drug that is generally considered to be fairly nontoxic and safe to use, even in patient populations such as elderly individuals who would be more prone to adverse events. When used in suicides, such as in this case, it is used with a lethal drug to prevent emesis and ensure a complete suicide.
This method is commonly advocated by various so-called "Exit" organizations that seek to educate people with terminal illnesses how to commit suicide in as painless a way as possible [5]. In addition to providing a how-to guide on the actual act of suicide, these organizations provide logistical support in the form of helping suicidal people place their affairs in order, as well as how to contend with local laws. Suicide is de-criminalized in the United States. However, assistance from others in most forms remains controversial and has the potential of legal consequences for those involved, depending on the state. Many of the methods in these guides, such as asphyxiation with helium, are not routinely tested for, and if the apparatus is removed prior to the arrival of medical examiners, could easily be ascribed to natural causes. It is in the best interests of medical examiners to become familiar with these sources of information and the methods they advocate, as they are shockingly easy to find both in print [6] and online [7]. While these organizations tout themselves as being for people who have a painful disease or severe degradation of their physical condition, there is no apparent "check" or validation, such as proof of diagnosis, to obtain the information. It is therefore simple for people suffering clinical depression to use this information as well. This is what happened in the above case, as the decedent was young, apparently healthy, and had no severe medical problems to speak of.
Our case presents two final learning points. First, in the case of decomposition, both pentobarbital and metoclopramide can be detected with samples of liver or spleen. However, it is advised that both be sent if possible, to ensure both detection and quantitation of the drugs responsible for death. Second, in cases where a "mystery liquid" is present at the scene, it is important to try and secure it in an airtight container as soon as possible to allow for future testing, if it becomes needed.
~*~
Journal of Forensic Science International 2017
The authors present an unusual fatal pentobarbital intoxication case, in a 37 years-old male salesperson, with no known connection with the veterinary field, being more difficult to obtain this compound.
Toxicological results in cardiac blood revealed the presence of pentobarbital (111 mg/L), ethanol (0.94 g/L), diazepam (33 ng/mL), nordiazepam (50 ng/mL), oxazepam (3.3 ng/mL), temazepam (5.3 ng/mL), and metoclopramide. No illicit drugs were detected.
Pentobarbital analysis in urine and gastric content was also positive, as well as its presence in the glass powder and in the bottle residue sent to the laboratory.
In the present case, it was possible to conclude that the death was a suicide due to pentobarbital intoxication in association with other depressants of the CNS (benzodiazepines and ethanol).
It is important to search pentobarbital in routine toxicological analyses, since it is one of the drugs most frequently mentioned by entities defending "painless death", advising the simultaneous use of metoclopramide for emesis avoidance.
~*~
Journal of Clinical Toxicology 2017
Sir,
In a previous edition, we described a regional phenomenon in which individuals were obtaining veterinary pentobarbital from Mexico for the purpose of committing suicide ("suicide tourism") [1]. Over the last two years, we have noticed an alarming increase in suicides involving pentobarbital within our county. This motivated us to retrospectively review Medical Examiner investigative and toxicology reports dating back to the year following our previous case series.
From January 2011 to June 2016, we identified 1, 2, 2, 2, 6 and 7 pentobarbital-related suicides, respectively. Peripheral pentobarbital blood concentrations ranged from 20 to >1000 mg/L. Ethanol and/or other medications were detected in 14 cases (70%) with an antiemetic being involved in 8 (40%). This is relevant given that pro-euthanasia resources often advocate taking an antiemetic prior to ingesting a lethal dose of a toxin [2]. The route of exposure was ingestion in 19 cases (95%) and intravenous in 1 case (veterinarian in his office). The decedents were found in: their homes 10 cases (50%), a hotel/motel 8 cases (40%), a car 1 case, and a veterinarian 1 case. Unfortunately, the source/type of pentobarbital was only documented in the case of the veterinarian (euthanasia solution from his practice).
~*~
Journal of Forensic Sciences 2018
In 11 cases, there was clear evidence (i.e., packaging and/or documentation) of mail order pentobarbital via internet purchase; in nine cases from Mexico and in two cases from China. In two additional cases, there was Spanish labeling on the pentobarbital vials. In the majority of cases where vials of liquid pentobarbital were present, there were one or two vials with a concentration of 6.3 g/100 mL.
In four cases a bag was found, with some remaining white powder that was either labeled as "fumaric acid" (3/4) or "potassium formate" (1/4). Two of the four powders, both labeled as "fumaric acid," were tested by Health Canada and found to contain pentobarbital instead of the labeled chemical. The drugs in these two cases appear to have been imported from China. In the other two cases, the bags were destroyed without being tested, and it was unclear whether they were imported.
Among the decedents, there was no trend in age; however, all individuals in the observed cases were over the age of 20. The decedents ranged from 21 to 90 years of age. In all of the cases, the manner of death was determined to be suicide. A suicide note or communication of the intent to die was documented in 14 of the 20 cases.
Depression or other mental illness was considered to be a factor in 13 cases (11: depression and six "other": bipolar mood disorder, schizoaffective disorder, schizophrenia, and anorexia nervosa). Some of the "other" mental health conditions were also present in cases where depression was noted. Physical illness was documented as a factor in eight cases. In three of these cases, the medical history documents both a mental health illness and a physical illness.
Reading materials on suicide methods were found in 6 cases. The Peaceful Pill was specifically mentioned in 3 cases and Final Exit was mentioned in one case. In the noted histories for two other cases, only generic references were made to reading material on suicide, but specific details were not provided.
Drugs with antiemetic properties were detected in 12 cases; however, not all cases were tested for all drugs. These drugs included diphenhydramine (8/12), ondansetron (1/12), and metoclopramide (3/12).
~*~
Pentobarbital (published by StatPearls on PubMed)
Toxic doses of pentobarbital occur at approximately 1 gram in most adults, with death occurring at 2 to 10 grams.
Treatment of pentobarbital toxicity involves supportive care, as there is no antidote. Overdose can lead to airway compromise, cardiovascular collapse, coma, and death. Treatment often requires intubation, hemodynamic support with vasopressors, and maintaining body temperature with warmers, commonly in an ICU setting. In mild or early cases of toxicity, activated charcoal and alkaline diuresis have been added but show minimal benefits. Always contact poison control if poisoning or overdose is suspected.
Dear Editor
We recently had a case with interesting toxicology results that we felt merited publication in the literature to bring attention to what could become a trend. While a similar case has been published recently [1], ours presented some unique learning points not otherwise covered.
The decedent was a 37-year-old white male, who was found unresponsive in his locked apartment in a moderate state of decomposition with skin discoloration, bloating, bullae formation, and skin slippage. He was seated and leaning over the back of a chair at a desk. The desk had a handwritten last will and testament and a bottle which contained a clear liquid. Autopsy did not reveal any signs of trauma, foul play, or obvious cause of death. Toxicology was sent; however, due to the state of decomposition, only liver, spleen, and cavity fluid were able to be sent to NMS Labs. The liver was positive for pentobarbital (190 µg/g) and metoclopramide (which could not be quantitated due to sample matrix issues); the spleen was positive for both pentobarbital (170 µg/g) and metoclopramide (56 μg/g). Directed analysis of the cavity fluid revealed a pentobarbital concentration of 670 µg/mL. Metoclopramide was detected in the cavity fluid as well, but there was insufficient sample for quantitation. The liquid found within the bottle by the decedent had evaporated in the postmortem interval, and was unable to be tested. A conversation with the family of the decedent revealed that he had often talked about suicide, but there were no known previous attempts. This case was ultimately signed out as pentobarbital toxicity, with suicide as the manner of death.
Pentobarbital belongs to the barbiturate class of medications and works via the GABA-A receptor to hyperpolarize neurons and cause generalized central nervous system depression. Barbiturates do this by acting as an agonist and are capable of directly opening the GABA-A receptor, keeping it open for a longer time. This is in contrast to benzodiazepines, which, while they work on the same receptor, have a different binding site and are unable to directly open the channel. Rather, they increase the potential for the channel to be opened by GABA. Having an effective antidote, fewer side effects, and more forgiving withdrawal are all reasons why benzodiazepines are preferred today [2]. Barbiturates in general are rarely used in the United States, although some indications, such as second or third line therapies for seizures or migraines still exist. Pentobarbital is used almost exclusively in this country for euthanizing animals, raising the concern that most people who commit suicide using it are in veterinary medicine [3].
Lethal levels for pentobarbital are considered to be about ten times the usual oral dose. Potential lethal blood concentrations are those in excess of 80 µg/mL [4]. Metoclopramide is an antiemetic drug that is generally considered to be fairly nontoxic and safe to use, even in patient populations such as elderly individuals who would be more prone to adverse events. When used in suicides, such as in this case, it is used with a lethal drug to prevent emesis and ensure a complete suicide.
This method is commonly advocated by various so-called "Exit" organizations that seek to educate people with terminal illnesses how to commit suicide in as painless a way as possible [5]. In addition to providing a how-to guide on the actual act of suicide, these organizations provide logistical support in the form of helping suicidal people place their affairs in order, as well as how to contend with local laws. Suicide is de-criminalized in the United States. However, assistance from others in most forms remains controversial and has the potential of legal consequences for those involved, depending on the state. Many of the methods in these guides, such as asphyxiation with helium, are not routinely tested for, and if the apparatus is removed prior to the arrival of medical examiners, could easily be ascribed to natural causes. It is in the best interests of medical examiners to become familiar with these sources of information and the methods they advocate, as they are shockingly easy to find both in print [6] and online [7]. While these organizations tout themselves as being for people who have a painful disease or severe degradation of their physical condition, there is no apparent "check" or validation, such as proof of diagnosis, to obtain the information. It is therefore simple for people suffering clinical depression to use this information as well. This is what happened in the above case, as the decedent was young, apparently healthy, and had no severe medical problems to speak of.
Our case presents two final learning points. First, in the case of decomposition, both pentobarbital and metoclopramide can be detected with samples of liver or spleen. However, it is advised that both be sent if possible, to ensure both detection and quantitation of the drugs responsible for death. Second, in cases where a "mystery liquid" is present at the scene, it is important to try and secure it in an airtight container as soon as possible to allow for future testing, if it becomes needed.
~*~
Journal of Forensic Science International 2017
The authors present an unusual fatal pentobarbital intoxication case, in a 37 years-old male salesperson, with no known connection with the veterinary field, being more difficult to obtain this compound.
Toxicological results in cardiac blood revealed the presence of pentobarbital (111 mg/L), ethanol (0.94 g/L), diazepam (33 ng/mL), nordiazepam (50 ng/mL), oxazepam (3.3 ng/mL), temazepam (5.3 ng/mL), and metoclopramide. No illicit drugs were detected.
Pentobarbital analysis in urine and gastric content was also positive, as well as its presence in the glass powder and in the bottle residue sent to the laboratory.
In the present case, it was possible to conclude that the death was a suicide due to pentobarbital intoxication in association with other depressants of the CNS (benzodiazepines and ethanol).
It is important to search pentobarbital in routine toxicological analyses, since it is one of the drugs most frequently mentioned by entities defending "painless death", advising the simultaneous use of metoclopramide for emesis avoidance.
~*~
Journal of Clinical Toxicology 2017
Sir,
In a previous edition, we described a regional phenomenon in which individuals were obtaining veterinary pentobarbital from Mexico for the purpose of committing suicide ("suicide tourism") [1]. Over the last two years, we have noticed an alarming increase in suicides involving pentobarbital within our county. This motivated us to retrospectively review Medical Examiner investigative and toxicology reports dating back to the year following our previous case series.
From January 2011 to June 2016, we identified 1, 2, 2, 2, 6 and 7 pentobarbital-related suicides, respectively. Peripheral pentobarbital blood concentrations ranged from 20 to >1000 mg/L. Ethanol and/or other medications were detected in 14 cases (70%) with an antiemetic being involved in 8 (40%). This is relevant given that pro-euthanasia resources often advocate taking an antiemetic prior to ingesting a lethal dose of a toxin [2]. The route of exposure was ingestion in 19 cases (95%) and intravenous in 1 case (veterinarian in his office). The decedents were found in: their homes 10 cases (50%), a hotel/motel 8 cases (40%), a car 1 case, and a veterinarian 1 case. Unfortunately, the source/type of pentobarbital was only documented in the case of the veterinarian (euthanasia solution from his practice).
~*~
Journal of Forensic Sciences 2018
In 11 cases, there was clear evidence (i.e., packaging and/or documentation) of mail order pentobarbital via internet purchase; in nine cases from Mexico and in two cases from China. In two additional cases, there was Spanish labeling on the pentobarbital vials. In the majority of cases where vials of liquid pentobarbital were present, there were one or two vials with a concentration of 6.3 g/100 mL.
In four cases a bag was found, with some remaining white powder that was either labeled as "fumaric acid" (3/4) or "potassium formate" (1/4). Two of the four powders, both labeled as "fumaric acid," were tested by Health Canada and found to contain pentobarbital instead of the labeled chemical. The drugs in these two cases appear to have been imported from China. In the other two cases, the bags were destroyed without being tested, and it was unclear whether they were imported.
Among the decedents, there was no trend in age; however, all individuals in the observed cases were over the age of 20. The decedents ranged from 21 to 90 years of age. In all of the cases, the manner of death was determined to be suicide. A suicide note or communication of the intent to die was documented in 14 of the 20 cases.
Depression or other mental illness was considered to be a factor in 13 cases (11: depression and six "other": bipolar mood disorder, schizoaffective disorder, schizophrenia, and anorexia nervosa). Some of the "other" mental health conditions were also present in cases where depression was noted. Physical illness was documented as a factor in eight cases. In three of these cases, the medical history documents both a mental health illness and a physical illness.
Reading materials on suicide methods were found in 6 cases. The Peaceful Pill was specifically mentioned in 3 cases and Final Exit was mentioned in one case. In the noted histories for two other cases, only generic references were made to reading material on suicide, but specific details were not provided.
Drugs with antiemetic properties were detected in 12 cases; however, not all cases were tested for all drugs. These drugs included diphenhydramine (8/12), ondansetron (1/12), and metoclopramide (3/12).
~*~
Pentobarbital (published by StatPearls on PubMed)
Toxic doses of pentobarbital occur at approximately 1 gram in most adults, with death occurring at 2 to 10 grams.
Treatment of pentobarbital toxicity involves supportive care, as there is no antidote. Overdose can lead to airway compromise, cardiovascular collapse, coma, and death. Treatment often requires intubation, hemodynamic support with vasopressors, and maintaining body temperature with warmers, commonly in an ICU setting. In mild or early cases of toxicity, activated charcoal and alkaline diuresis have been added but show minimal benefits. Always contact poison control if poisoning or overdose is suspected.
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