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Veterinary euthanasia drugs as suicide agents
CASE REPORTS drugs, veterinary euthanasia, suicide; suicide, drugs, veterinary
Veterinary Euthanasia Drugs as Suicide Agents We report three cases in which pentobarbital and T-61® were used or their use was threatened in suicide attempts. One patient died after IV injection of a pentobarbital solution. Another threatened suicide by the same method. A third patient survived the ingestion of both pentobarbital and T-61®. Supportive care forms the mainstay of therapy when these agents are used in suicide attempts. [Cordell WH, Curry SC, Furbee RB, Mitchell-Flynn DL: Veterinary euthanasia drugs as suicide agents. A n n Emerg Med August 1986;15:939-943.] INTRODUCTION Two commonly used pharmaceutical preparations for the euthanasia of animals are concentrated solutions of pentobarbital and T-61 ®. Concentrated solutions of pentobarbital for parenteral administration are available under a variety of trade names {Table). These solutions produce rapid central nervous system (CNS) depression and cardiovascular collapse. 1 T-61 ® is a commercial product also intended for parenteral administration. Its ingredients include embutramide, a general anesthetic, and mebezonium, a neuromuscular blocking agent with actions similar to those of curare. Rare reports of human beings using veterinary euthanasia agents to comInit suicide have appeared. 2-5 We cared for three patients who attempted or threatened suicide by self-administration of these agents, making us believe that their use in suicides may be more common than the literature reflects. All three were veterinary personnel who had access to pentobarbital and/or T-61 ®. The first patient died from a self-administered injection of pentobarbital; the second threatened suicide by the same method. The third survived a suicide attempt in which both pentobarbital and T-61® were ingested.
William H Cordell, MD, FACEP* Steven C Curry, MD, FACEP, ABMT1R Brent Furbee, MD, FACEP* David L MitchelI-Flynn, MD* Indianapolis, Indiana Phoenix, Arizona Lafayette, Indiana From the Emergency Medicine and Trauma Center, Methodist Hospital of Indiana, Inc, Indianapolis, Indiana;* the Central Arizona Regional Poison Management Center, and the Department of Medical Toxicology, St Luke's Medical Center, Phoenix, Arizona;l and the Department of Emergency Medicine, St Elizabeth Hospital Medical Center, Lafayette, Indiana.* Received for publication August 22, 1985. Accepted for publication September 24, 1985. Address for reprints: William H Cordell, MD, Emergency Medicine and Trauma Center, Methodist Hospital of Indiana, 1604 North Capitol Avenue, Indianapolis, Indiana 46202.
CASE REPORTS Case Number One A 17-year-old man was found pulseless and apneic on the floor of the veterinary clinic where he was employed with a needle attached to a partially emptied syringe still inserted in his right antecubital fossa. A multidose vial of Socumb ® {Figure), a veterinary euthanasia agent containing 360 mg/mL pentobarbital, was found nearby. Bystander CPR was initiated while a basic life support unit was summoned. Bag-valve-mask ventilation and external cardiac complessions were continued during transport to the hospital. On arrival the patient was in asystole. Endotracheal intubation and the administration of IV 1 ampule epinephrine, 3 ampules sodium bicarbonate, and isoproterenol in D5W resulted in the development of sinus tachycardia of 150 beats per minute and a blood pressure of 112/0 m m Hg. The patient was flaccid, made no response to pain, had no respiratory activity, and had pupils in midposition that were unreactive to light. An indwelling urinary catheter was inserted with the return of pink urine that was negative for blood when tested with a dip stick. The patient was transported by helicopter to a pediatric critical care center. Shortly after admission a bedside isotope brain flow study showed normal flow. The day following admission the pupils were slightly reactive. Occasional spontaneous breaths were noted, although there was no gag reflex and no response to painful stimuli. Infusions of both dopamine a n d nor15:8 August 1986
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SUICIDE AGENTS Cordell et al
epinephrine were required to maintain an adequate blood pressure. Urinalysis four hours after the suicide attempt showed numerous red blood cells. A serum pentobarbital level drawn approximately four hours after injection of the drug was 30.7 p,g/mL (therapeutic level, 1 to 5 ~g/mL). On the third day of hospitalization the patient experienced two episodes of fixed and dilated pupils. In both instances, the p u p i l l a r y reflexes returned after the administration of IV mannitol and hyperventilation. Computed tomography scan of the brain showed cerebral edema with lesions in the basal ganglia compatible with severe brain hypoxia. By the ninth day of hospitalization, all cerebral activity had ceased and an isotope cerebral blood flow s t u d y showed no cerebral perfusion. Lifesupport systems were withdrawn.
Case Number Two A 29-year-old w o m a n called her mother and threatened to commit suicide by injecting a drug obtained from the animal clinic where she worked. Minutes later she was found unresponsive by paramedics. An attempt at endotracheal intubation was unsuccessful, but it did result in an increased level of consciousness. A nearly empty bottle of Sleepaway ® conraining 260 mg sodium pentobarbital per milliliter was found nearby. In addition, paramedics found "nine dead cats stacked in a row" in her home. On admission the patient was lethargic, but answered questions appropriately. No needle p u n c t u r e sites were noted. Gastric lavage was performed and was followed by the administration of 30 g activated charcoal. The patient admitted only to drinking wine. She was observed in the emergency department until fully awake and then was transported to the psychiatric unit for further evaluation. The patient stated that she had injected her cats because they had leukemia.
Case Number Three A 39-year-old depressed veterinarian was found unconscious and "barely breathing" by his wife, who telep h o n e d the ED. I n s t r u c t i o n s for m o u t h - t o - m o u t h resuscitation were given by telephone and paramedics were dispatched. T h e y arrived five m i n u t e s after the initial call and found the patient apneic with a pulse 128/940
TABLE. Products commonly used for veterinary euthanasia Brand Name
Beuthanasia-D Special ®
Manufacturer
Ingredients
Burns-Biotec
390 mg/mL Na pentobarbital 50 mg/mL phenytoin 18% propylene glycol 10% alcohol Euthanasia Med-Tech 325 mg/mL Na Solution® pentobarbital Propylene glycol Alcohol Fatal® North American 325 mg/mL Na Pharmacal pentobarbital Propylene glycol Alcohol Lethal ® Eli Lilly 260 mg/mL Na pentobarbital Isopropanol 20% polyethylene glycol-200 Repose ® Diamond 400 mg/mL secobarbital 50 mg mephenesin 10% propylene glycol Sleepaway® Fort Dodge 260 mg/mL Na pentobarbital 10% isopropanol 20% propylene glycol Socumb ® The Butler Company 360 mg/mL Na pentobarbital 31.2% isopropanol 2.38% propylene glycol T-61 ® American Hoechst 200 mg/mL embutramide* 50 mg/mL mebezoniumt 5 mg/mL tetracaine 0.6 mL dimethylformamide/ mL 1--61® *N-[2-(m-methoxy-phenyl)-2-ethyl-butyl-(1)]-garnma-hyd roxy-butyramide. t4,4-methylene-bis (cyclohexyl-trimethyl-ammoniumiodide). of 80 and a blood pressure of 80/50 m m Hg. The pupils were midposition and reactive. There was no cyanosis. The patient's wife stated that she had last seen her husband three hours earlier. She said that in the interim he had ingested 15 mL T-61®and as much as 50 mL of an unknown brand of sodium pentobarbital (65 mg/mL) mixed in a fruit juice. Paramedics performed endotracheal i n t u b a t i o n and ventilated the patient with 100% oxygen using a resuscitator bag. A 16-gauge IV catheter was placed and 1 L normal saline was started at a wide-open rate. On arrival 23 minutes after the call, the patient's blood pressure was 48/0 rnm Hg and his pulse was 42. The cardiac monitor showed sinus bradycarAnnals of Emergency Medicine
dia. The pupils were constricted and nonreactive. The patient was areflexic and apneic, and made no response to pain. Examination of the chest, heart, skin, and abdomen was otherwise unremarkable. Initial treatment included the placement of military antishock trousers, further fluid challenges with 2.5 L crystalloid, and 500 mL hetastarch, sodium bicarbonate, and a phenylephrine drip. With this treatment blood pressure rose to 158/74 m m Hg and the pulse rose to 54. Gastric lavage was p e r f o r m e d and 30 g activated charcoal was placed in the stomach. Foley c a t h e t e r i z a t i o n yielded clear urine. A chest radiograph was normal. A complete blood count, electrolytes,
15:8 August 1986
FIGURE. Needle and syringe containing blood from aspiration and bottle of Socumb ® used in Case 1.
and a SMA12 were all normal except for a white blood cell count of 21,000/ ram3 with a differential of 24 segments, 62 bands, and 6 lymphocytes. A serum pentobarbital level was 6.1 wg/mL. Two hours after arrival, his blood pressure was 106/98 m m Hg while off the phenylephrine and while receiving IV fluids at a keep-open rate. The p u p i l s w e r e m i d p o s i t i o n and responded slowly to light. The patient was moved to the intensive care unit about three hours after admission and was placed on a ventilator. His rectal temperature was 32.7 C. He was actively externally rew a r m e d using a h e a t i n g blanket. Spontaneous movements of the lower extremities and spontaneous respirations were noted about nine hours after admission. The patient was extubated on the third day. On the fourth day he squeezed his wife's hand on command, and his deep tendon reflexes were 2 + and symmetrical. The remainder of his 22-day hospital course included complete neurological recovery, but was complicated by p u l m o n a r y infiltrates and fever thought to be secondary to aspiration and by t r a n s i e n t l y elevated liver enzymes. The patient made a complete recovery and was able to return to work several months later.
DISCUSSION Injectable pentobarbital solutions and T-61 ® are two c o m m o n phar15:8 August 1986
maceutical agents used for killing animals.
Pentobarbital Massive barbiturate poisoning in h u m a n beings is characterized by coma with respiratory depression, cardiovascular collapse, and hypothermia. 6 Because pentobarbital euthanasia solutions are concentrated and have a rapid onset of action w h e n given ~ asystole and death can follow within several seconds after injection into animals (personal c o m m u n i c a tion, Peter Bates, DVM, Phoenix, Arizona). Sodium pentobarbital is well absorbed from the gastrointestinal tract and following parenteral injection. 7 Art oral dose of 100 mg sodium pentobarbital will have a hypnotic effect in an adult human being. 7 Because a parenteral sodium pentobarbital solution used for veterinary euthanasia may contain more than 300 m g / m L sodium pentobarbital, the severe toxicity of small quantities of these solutions following injection or ingestion may be appreciated. Patient 1 was found w i t h an incompletely emptied syringe and needle in an antecubital vein. Although the patient was resuscitated initially, he suffered severe anoxic-ischemic encephalopathy from a prolonged cardiopulmonary arrest, culminating in cerebral death. Two other cases of suicide in which veterinary euthanasia solutions conAnnals of Emergency Medicine
taining barbiturates were used have been reported in the medical literature. Clark and Jones 2 reported the case of a 20-year-old man who committed suicide by the parenteral administration of the veterinary euthanasia agent Lethal ®, which contains both pentobarbital and amobarbital. As in Patient 1, a needle was found in the antecubital fossa, emphasizing the rapid onset of action of these solutions. The p o s t m o r t e m blood pentobarbital concentration was 45 ~g/ mL. Poklis and H a m e l i 3 reported the case of a veterinarian who was found dead after ingesting an u n k n o w n quantity of Toxital ®, which contained sodium pentobarbital as the active ingredient. The postmortem blood pen: tobarbital concentration was 150 txg/ mL. Barbiturate solutions used in veterinary euthanasia frequently contain such glycols as propylene glycol. Toxic doses of propylene glycol can cause hyperosmolality, acidosis, and CNS depression, and may contribute to the t o x i c i t y of these solutions. 8ql In sheep, the IV injection of s o d i u m pentobarbital with propylene glycol r e s u l t s in h e m o l y s i s and h e m o globinuria. 12 Patient 1 did have pink urine on insertion of an indwelling catheter, but it was probably due to hematuria secondary to trauma from the insertion of the Foley catheter because red blood cells were noted on microscopic examination of the urine. T-61 ® T-61 ® has been used for euthanasia of a variety of animal species in Germany since 1962 and in the United States since 1963.1 It is available in multidose vials with each milliliter containing 200 mg embutramide, 50 mg mebezonium, 5 nag tetracaine, and 0.6 mL of the solvent dimethylformamide (DMF). Embutramide, a general anesthetic, produces a rapid loss of consciousness and respiratory arrest after IV injection. In the dog, doses of 25 mg/kg rapidly produce anesthesia that lasts 45 minutes. 12 Embutramide can be absorbed from the gastrointestinal (GI) tract, although the toxic dose is not well defined. Rats can survive an oral dose of 50 mg/kg.12 One dog died after 941/129
SUICIDE AGENTS Cordell et al
the oral administration of 0.5 mL/kg of T-61®; another recovered from anesthesia induced by an oral dose of 0.1 m L / k g T-61 ®. Our patient ingested more than 0.18 mL/kg T-61 ® (3 g embutramide). Mebezonium is a curare derivative that was synthesized in 1954 by the Ciba Company, 4 but was never promoted for experimental and clinical research. It is a muscle relaxant that is a competitive inhibitor of acetylcholine at nicotinic receptors. The action of mebezonium is reversed with such anticholinesterase agents as pyridostigrnine and physostigmine.4, n A dose capable of producing respiratory arrest in dogs varies from 1 to 2 mg/kg IV; 13 in dogs the curare effect lasts at least one hour. Like all curare derivatives, mebezonium is poorly absorbed from the GI tract. Rats have survived oral doses of 50 mg/kg; guinea pigs die in respiratory arrest following 200 rag/ kg. 13 The 15 mL of T-61® our patient ingested contained 750 mg mebezonium. The tetracaine present in T-61® permits complete injection without pain or struggling. Like all local anesthetics, toxic doses of tetracaine can cause CNS stimulation with restlessness, tremors, and convulsions. TM The solvent in T-61®, DMF, is not entirely free from toxicity, although fairly large amounts are required to produce adverse effects. The approximate lethal dose (ALD) orally in rats is 2,250 mg/kg. 13 Repeated doses administered by inhalation, oral ingestion, or dermal exposure have produced multisystem effects with lung, liver, and renal damage. 13 T-61® has been found to induce euthanasia s m o o t h l y w i t h o u t undesirable reactions, and is just as effective as pentobarbital for this purpose.1 When T-61® is administered parenterally in v e t e r i n a r y practice, embutramide alone is present in sufficient quantity to cause euthanasia by CNS depression and respiratory arrest. The addition of the mebezonium ensures that respirations cannot resume. In 1982, Cavaliere and colleagues reported a case in which a mother injected herself and her two children with unknown quantities of T-61 ®in a murder-suicide attempt. 4 An e m p t y 50-mL vial of T-61 ® was found at the scene, indicating that the total volu m e of the drug administered was probably not more than 50 mL. The 7year-old gift was dead on arrival at the 130/942
ED. Her 6-year-old brother was comatose, with respiratory depression and cyanosis of mucous membranes. His blood pressure was 80/50 m m Fig and the pulse was 140. Corneal reflexes were present, and pupils were equal, slightly constricted, and sluggishly reactive to light. Except for decreased deep tendon reflexes, the remainder of the physical examination was unremarkable. Oxygen was administered, and within four hours, the child was awake and alert. On arrival the mother was comatose and suffering from generalized convulsions. The pupils were equal, slightly dilated, and slightly reactive to light. Vital signs were as follows: blood pressure, 100/80 m m Fig; pulse, 110; temperature, 36.5 C; and respirations, 25 to 30 with periods of apnea lasting for 15 seconds. It was during apnea t h a t c o n v u l s i o n s i n v o l v i n g mainly the arms were noted. Auscultation of the chest revealed vesicular breath sounds and tales. Endotracheal intubation was performed, and respiratory assistance using 40% oxygen was given. Convulsions were controlled with diazepam. Within four hours the patient was markedly improved, w i t h a blood pressure of 120/70 m m Hg, pulse of 90, and normal respirations. It is assumed that she regained consciousness, although this was not noted specifically. Kingston and Saxena s reported the case of a 20-year-old woman who injected 12 m L T-61 ® intramuscularly and presented to an ED comatose, seizing, and in respiratory arrest. She recovered quickly after respiratory support and resuscitative measures. Patient 3 did not inject, but ingested, both T-61 e and a pentobarbital solution. No a t t e m p t was made to identify embutramide, mebezonium, or tetracaine in biological fluids. It is not possible to completely separate the effects of pentobarbital, embutramide, and transient cerebral hypoxia. Pentobarbital would not be expected to produce a significant neurological deficit two to three days after admission considering that the original serum pentobarbital concentration was only 6.1 v~g/mL. Cavaliere's two patients who were injected with T-61 ®4 and the 20-year-old woman reported by Kingston and Saxena s were both markedly improved within four hours, making it difficult to attribute a neurological deficit of several days to Annals of Emergency Medicine
the T-61. ® Anesthetic doses of embutramide in the dog last about 45 minutes. The prolonged neurological recovery in our patient was most likely due to slow recovery from cerebral hypoxia that resulted from respiratory depression and/or hypotension induced by T-61® and pentobarbital. The curare-like drug m e b e z o n i u m is not well absorbed from the GI tract, making respiratory failure from skeletal muscle weakness or paralysis unlikely. The etiology of the seizures noted in two of the previously reported cases of T-61 ® poisoning is not clear. Although toxic doses of tetracaine may induce seizures, hypoxia m a y have played a major role.
Treatment The treatment of pentobarbital poisoning consists mainly of supportive care. If the pentobarbital solution is ingested, gastric lavage and the administration of activated charcoal should be undertaken. In massive overdoses in which the patient continues to deteriorate in spite of supportive care, charcoal hemoperfusion may be effective.6 An alkaline diuresis does not enhance the elimination of pentobarbital. 6 Although adequate experience in treating poisoning with T-61~ is lacking, it seems that supportive care is the mainstay of therapy. Seizures have not been difficult to control with adequate oxygenation and diazepam. If musculoskeletal paralysis is present, it can be reversed by such anticholinesterase agents as pyridostigmine. Embutramide itself, however, can produce a respiratory arrest f r o m profound CNS depression. Decontamination of the GI tract with gastric lavage and activated charcoal also would be reasonable following the oral ingestion of T-61®. Our experience, along with reports in the medical literature, indicate that most persons who a t t e m p t suicide with veterinary euthanasia agents are employed in the field of veterinary medicine. SUMMARY When confronted with a comatose patient who has access to veterinary preparations, the emergency physician should consider the possibility that a veterinary euthanasia agent has been used in a suicide attempt. The most commonly used pharmaceutical 15:8 August 1986
agents, p e n t o b a r b i t a l s o l u t i o n s and T-61 ®, can cause rapid and profound C N S d e p r e s s i o n , r e s p i r a t o r y arrest, and cardiovascular collapse. Because no specific a n t i d o t e exists for these agents, supportive care appears to be the m a i n s t a y of therapy.
REFERENCES 1. Lumb W~, Doshi K, Scott RF: A comparative study of T-61 and pentobarbital for euthanasia of dogs. JAVMA 1978; 172:149-152. 2. Clark MA, Jones JW: Suicide by intravenous i n j e c t i o n of a v e t e r i n a r y euthanasia agent: Report of a case and toxicologic studies. J Forensic Sci 1979; 24:762-767. 3. Poklis A, Hameli AZ: Two unusual barbiturate deaths. Arch Toxicol 1975; 34:77-80.
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4. Cavaliere U, Andreano C, Raducci B, et al: Intossicazione da T 61 (Tanax). Minerva Anestesiol 1982;48:861-864. 5. Kingston RL, Saxena K: Intentional poisoning by injection of veterinary euthanasia drug (abstract). Clin Toxicol 1979;15:492. 6. Winchester IF: Barbiturates (including primidone), in Haddad LM, Winchester JF (eds): Poisoning and Drug Overdose, ed 1. Philadelphia, WB Saunders Co, 1983, pp 413-424. 7. Harvey SC: Hypnotics and sedatives, in Gilman AG, Goodman LS, Gilman A (eds): The Pharmacological Basis of Therapeutics, ed 6. New York, Macmillan Publishing Co, 1980, pp 339-375. 8. Glasgow AM, Boickx RL, Miller MK, et al: Hyperosmolality in small infants due to p r o p y l e n e glycol. Pediatrics 1983; 72:353-355. 9. Martin G, Finberg L: Propylene glycol:
Annals of Emergency Medicine
A potentially toxic vehicle in liquid dosage form. I Pediatr 1970;77:877-878. 10. Cate JC, Hedrick R: Propylene glycol intoxication and lactic acidosis (letter). N Engl l Med 1980;303:1237. 11. Arulanantham K, Genel M: Central nervous system toxicity associated with ingestion of propylene glycol. / Pediatr 1978;93:515-516. 12. Potter BJ: Haemoglobinuria caused by propylene glycol in sheep. Brit l Pharmacol 1958;13:385-389. 13. Product information supplied in personal c o m m u n i c a t i o n by RK Muser, DVM, Hoechst-Roussel Agri-Vet Company, 1985. 14. Ritchie JM, Greene NM: Local anesthetics, in Gilman AG, Goodman LS, Gilman A leds): The Pharmacological Basis of Therapeutics, ed 6. New York, M a c m i l l a n P u b l i s h i n g Co, 1980, pp 300-320.
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Veterinary Euthanasia Drugs as Suicide Agents We report three cases in which pentobarbital and T-61® were used or their use was threatened in suicide attempts. One patient died after IV injection of a pentobarbital solution. Another threatened suicide by the same method. A third patient survived the ingestion of both pentobarbital and T-61®. Supportive care forms the mainstay of therapy when these agents are used in suicide attempts. [Cordell WH, Curry SC, Furbee RB, Mitchell-Flynn DL: Veterinary euthanasia drugs as suicide agents. A n n Emerg Med August 1986;15:939-943.] INTRODUCTION Two commonly used pharmaceutical preparations for the euthanasia of animals are concentrated solutions of pentobarbital and T-61 ®. Concentrated solutions of pentobarbital for parenteral administration are available under a variety of trade names {Table). These solutions produce rapid central nervous system (CNS) depression and cardiovascular collapse. 1 T-61 ® is a commercial product also intended for parenteral administration. Its ingredients include embutramide, a general anesthetic, and mebezonium, a neuromuscular blocking agent with actions similar to those of curare. Rare reports of human beings using veterinary euthanasia agents to comInit suicide have appeared. 2-5 We cared for three patients who attempted or threatened suicide by self-administration of these agents, making us believe that their use in suicides may be more common than the literature reflects. All three were veterinary personnel who had access to pentobarbital and/or T-61 ®. The first patient died from a self-administered injection of pentobarbital; the second threatened suicide by the same method. The third survived a suicide attempt in which both pentobarbital and T-61® were ingested.
William H Cordell, MD, FACEP* Steven C Curry, MD, FACEP, ABMT1R Brent Furbee, MD, FACEP* David L MitchelI-Flynn, MD* Indianapolis, Indiana Phoenix, Arizona Lafayette, Indiana From the Emergency Medicine and Trauma Center, Methodist Hospital of Indiana, Inc, Indianapolis, Indiana;* the Central Arizona Regional Poison Management Center, and the Department of Medical Toxicology, St Luke's Medical Center, Phoenix, Arizona;l and the Department of Emergency Medicine, St Elizabeth Hospital Medical Center, Lafayette, Indiana.* Received for publication August 22, 1985. Accepted for publication September 24, 1985. Address for reprints: William H Cordell, MD, Emergency Medicine and Trauma Center, Methodist Hospital of Indiana, 1604 North Capitol Avenue, Indianapolis, Indiana 46202.
CASE REPORTS Case Number One A 17-year-old man was found pulseless and apneic on the floor of the veterinary clinic where he was employed with a needle attached to a partially emptied syringe still inserted in his right antecubital fossa. A multidose vial of Socumb ® {Figure), a veterinary euthanasia agent containing 360 mg/mL pentobarbital, was found nearby. Bystander CPR was initiated while a basic life support unit was summoned. Bag-valve-mask ventilation and external cardiac complessions were continued during transport to the hospital. On arrival the patient was in asystole. Endotracheal intubation and the administration of IV 1 ampule epinephrine, 3 ampules sodium bicarbonate, and isoproterenol in D5W resulted in the development of sinus tachycardia of 150 beats per minute and a blood pressure of 112/0 m m Hg. The patient was flaccid, made no response to pain, had no respiratory activity, and had pupils in midposition that were unreactive to light. An indwelling urinary catheter was inserted with the return of pink urine that was negative for blood when tested with a dip stick. The patient was transported by helicopter to a pediatric critical care center. Shortly after admission a bedside isotope brain flow study showed normal flow. The day following admission the pupils were slightly reactive. Occasional spontaneous breaths were noted, although there was no gag reflex and no response to painful stimuli. Infusions of both dopamine a n d nor15:8 August 1986
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939/127
SUICIDE AGENTS Cordell et al
epinephrine were required to maintain an adequate blood pressure. Urinalysis four hours after the suicide attempt showed numerous red blood cells. A serum pentobarbital level drawn approximately four hours after injection of the drug was 30.7 p,g/mL (therapeutic level, 1 to 5 ~g/mL). On the third day of hospitalization the patient experienced two episodes of fixed and dilated pupils. In both instances, the p u p i l l a r y reflexes returned after the administration of IV mannitol and hyperventilation. Computed tomography scan of the brain showed cerebral edema with lesions in the basal ganglia compatible with severe brain hypoxia. By the ninth day of hospitalization, all cerebral activity had ceased and an isotope cerebral blood flow s t u d y showed no cerebral perfusion. Lifesupport systems were withdrawn.
Case Number Two A 29-year-old w o m a n called her mother and threatened to commit suicide by injecting a drug obtained from the animal clinic where she worked. Minutes later she was found unresponsive by paramedics. An attempt at endotracheal intubation was unsuccessful, but it did result in an increased level of consciousness. A nearly empty bottle of Sleepaway ® conraining 260 mg sodium pentobarbital per milliliter was found nearby. In addition, paramedics found "nine dead cats stacked in a row" in her home. On admission the patient was lethargic, but answered questions appropriately. No needle p u n c t u r e sites were noted. Gastric lavage was performed and was followed by the administration of 30 g activated charcoal. The patient admitted only to drinking wine. She was observed in the emergency department until fully awake and then was transported to the psychiatric unit for further evaluation. The patient stated that she had injected her cats because they had leukemia.
Case Number Three A 39-year-old depressed veterinarian was found unconscious and "barely breathing" by his wife, who telep h o n e d the ED. I n s t r u c t i o n s for m o u t h - t o - m o u t h resuscitation were given by telephone and paramedics were dispatched. T h e y arrived five m i n u t e s after the initial call and found the patient apneic with a pulse 128/940
TABLE. Products commonly used for veterinary euthanasia Brand Name
Beuthanasia-D Special ®
Manufacturer
Ingredients
Burns-Biotec
390 mg/mL Na pentobarbital 50 mg/mL phenytoin 18% propylene glycol 10% alcohol Euthanasia Med-Tech 325 mg/mL Na Solution® pentobarbital Propylene glycol Alcohol Fatal® North American 325 mg/mL Na Pharmacal pentobarbital Propylene glycol Alcohol Lethal ® Eli Lilly 260 mg/mL Na pentobarbital Isopropanol 20% polyethylene glycol-200 Repose ® Diamond 400 mg/mL secobarbital 50 mg mephenesin 10% propylene glycol Sleepaway® Fort Dodge 260 mg/mL Na pentobarbital 10% isopropanol 20% propylene glycol Socumb ® The Butler Company 360 mg/mL Na pentobarbital 31.2% isopropanol 2.38% propylene glycol T-61 ® American Hoechst 200 mg/mL embutramide* 50 mg/mL mebezoniumt 5 mg/mL tetracaine 0.6 mL dimethylformamide/ mL 1--61® *N-[2-(m-methoxy-phenyl)-2-ethyl-butyl-(1)]-garnma-hyd roxy-butyramide. t4,4-methylene-bis (cyclohexyl-trimethyl-ammoniumiodide). of 80 and a blood pressure of 80/50 m m Hg. The pupils were midposition and reactive. There was no cyanosis. The patient's wife stated that she had last seen her husband three hours earlier. She said that in the interim he had ingested 15 mL T-61®and as much as 50 mL of an unknown brand of sodium pentobarbital (65 mg/mL) mixed in a fruit juice. Paramedics performed endotracheal i n t u b a t i o n and ventilated the patient with 100% oxygen using a resuscitator bag. A 16-gauge IV catheter was placed and 1 L normal saline was started at a wide-open rate. On arrival 23 minutes after the call, the patient's blood pressure was 48/0 rnm Hg and his pulse was 42. The cardiac monitor showed sinus bradycarAnnals of Emergency Medicine
dia. The pupils were constricted and nonreactive. The patient was areflexic and apneic, and made no response to pain. Examination of the chest, heart, skin, and abdomen was otherwise unremarkable. Initial treatment included the placement of military antishock trousers, further fluid challenges with 2.5 L crystalloid, and 500 mL hetastarch, sodium bicarbonate, and a phenylephrine drip. With this treatment blood pressure rose to 158/74 m m Hg and the pulse rose to 54. Gastric lavage was p e r f o r m e d and 30 g activated charcoal was placed in the stomach. Foley c a t h e t e r i z a t i o n yielded clear urine. A chest radiograph was normal. A complete blood count, electrolytes,
15:8 August 1986
FIGURE. Needle and syringe containing blood from aspiration and bottle of Socumb ® used in Case 1.
and a SMA12 were all normal except for a white blood cell count of 21,000/ ram3 with a differential of 24 segments, 62 bands, and 6 lymphocytes. A serum pentobarbital level was 6.1 wg/mL. Two hours after arrival, his blood pressure was 106/98 m m Hg while off the phenylephrine and while receiving IV fluids at a keep-open rate. The p u p i l s w e r e m i d p o s i t i o n and responded slowly to light. The patient was moved to the intensive care unit about three hours after admission and was placed on a ventilator. His rectal temperature was 32.7 C. He was actively externally rew a r m e d using a h e a t i n g blanket. Spontaneous movements of the lower extremities and spontaneous respirations were noted about nine hours after admission. The patient was extubated on the third day. On the fourth day he squeezed his wife's hand on command, and his deep tendon reflexes were 2 + and symmetrical. The remainder of his 22-day hospital course included complete neurological recovery, but was complicated by p u l m o n a r y infiltrates and fever thought to be secondary to aspiration and by t r a n s i e n t l y elevated liver enzymes. The patient made a complete recovery and was able to return to work several months later.
DISCUSSION Injectable pentobarbital solutions and T-61 ® are two c o m m o n phar15:8 August 1986
maceutical agents used for killing animals.
Pentobarbital Massive barbiturate poisoning in h u m a n beings is characterized by coma with respiratory depression, cardiovascular collapse, and hypothermia. 6 Because pentobarbital euthanasia solutions are concentrated and have a rapid onset of action w h e n given ~ asystole and death can follow within several seconds after injection into animals (personal c o m m u n i c a tion, Peter Bates, DVM, Phoenix, Arizona). Sodium pentobarbital is well absorbed from the gastrointestinal tract and following parenteral injection. 7 Art oral dose of 100 mg sodium pentobarbital will have a hypnotic effect in an adult human being. 7 Because a parenteral sodium pentobarbital solution used for veterinary euthanasia may contain more than 300 m g / m L sodium pentobarbital, the severe toxicity of small quantities of these solutions following injection or ingestion may be appreciated. Patient 1 was found w i t h an incompletely emptied syringe and needle in an antecubital vein. Although the patient was resuscitated initially, he suffered severe anoxic-ischemic encephalopathy from a prolonged cardiopulmonary arrest, culminating in cerebral death. Two other cases of suicide in which veterinary euthanasia solutions conAnnals of Emergency Medicine
taining barbiturates were used have been reported in the medical literature. Clark and Jones 2 reported the case of a 20-year-old man who committed suicide by the parenteral administration of the veterinary euthanasia agent Lethal ®, which contains both pentobarbital and amobarbital. As in Patient 1, a needle was found in the antecubital fossa, emphasizing the rapid onset of action of these solutions. The p o s t m o r t e m blood pentobarbital concentration was 45 ~g/ mL. Poklis and H a m e l i 3 reported the case of a veterinarian who was found dead after ingesting an u n k n o w n quantity of Toxital ®, which contained sodium pentobarbital as the active ingredient. The postmortem blood pen: tobarbital concentration was 150 txg/ mL. Barbiturate solutions used in veterinary euthanasia frequently contain such glycols as propylene glycol. Toxic doses of propylene glycol can cause hyperosmolality, acidosis, and CNS depression, and may contribute to the t o x i c i t y of these solutions. 8ql In sheep, the IV injection of s o d i u m pentobarbital with propylene glycol r e s u l t s in h e m o l y s i s and h e m o globinuria. 12 Patient 1 did have pink urine on insertion of an indwelling catheter, but it was probably due to hematuria secondary to trauma from the insertion of the Foley catheter because red blood cells were noted on microscopic examination of the urine. T-61 ® T-61 ® has been used for euthanasia of a variety of animal species in Germany since 1962 and in the United States since 1963.1 It is available in multidose vials with each milliliter containing 200 mg embutramide, 50 mg mebezonium, 5 nag tetracaine, and 0.6 mL of the solvent dimethylformamide (DMF). Embutramide, a general anesthetic, produces a rapid loss of consciousness and respiratory arrest after IV injection. In the dog, doses of 25 mg/kg rapidly produce anesthesia that lasts 45 minutes. 12 Embutramide can be absorbed from the gastrointestinal (GI) tract, although the toxic dose is not well defined. Rats can survive an oral dose of 50 mg/kg.12 One dog died after 941/129
SUICIDE AGENTS Cordell et al
the oral administration of 0.5 mL/kg of T-61®; another recovered from anesthesia induced by an oral dose of 0.1 m L / k g T-61 ®. Our patient ingested more than 0.18 mL/kg T-61 ® (3 g embutramide). Mebezonium is a curare derivative that was synthesized in 1954 by the Ciba Company, 4 but was never promoted for experimental and clinical research. It is a muscle relaxant that is a competitive inhibitor of acetylcholine at nicotinic receptors. The action of mebezonium is reversed with such anticholinesterase agents as pyridostigrnine and physostigmine.4, n A dose capable of producing respiratory arrest in dogs varies from 1 to 2 mg/kg IV; 13 in dogs the curare effect lasts at least one hour. Like all curare derivatives, mebezonium is poorly absorbed from the GI tract. Rats have survived oral doses of 50 mg/kg; guinea pigs die in respiratory arrest following 200 rag/ kg. 13 The 15 mL of T-61® our patient ingested contained 750 mg mebezonium. The tetracaine present in T-61® permits complete injection without pain or struggling. Like all local anesthetics, toxic doses of tetracaine can cause CNS stimulation with restlessness, tremors, and convulsions. TM The solvent in T-61®, DMF, is not entirely free from toxicity, although fairly large amounts are required to produce adverse effects. The approximate lethal dose (ALD) orally in rats is 2,250 mg/kg. 13 Repeated doses administered by inhalation, oral ingestion, or dermal exposure have produced multisystem effects with lung, liver, and renal damage. 13 T-61® has been found to induce euthanasia s m o o t h l y w i t h o u t undesirable reactions, and is just as effective as pentobarbital for this purpose.1 When T-61® is administered parenterally in v e t e r i n a r y practice, embutramide alone is present in sufficient quantity to cause euthanasia by CNS depression and respiratory arrest. The addition of the mebezonium ensures that respirations cannot resume. In 1982, Cavaliere and colleagues reported a case in which a mother injected herself and her two children with unknown quantities of T-61 ®in a murder-suicide attempt. 4 An e m p t y 50-mL vial of T-61 ® was found at the scene, indicating that the total volu m e of the drug administered was probably not more than 50 mL. The 7year-old gift was dead on arrival at the 130/942
ED. Her 6-year-old brother was comatose, with respiratory depression and cyanosis of mucous membranes. His blood pressure was 80/50 m m Fig and the pulse was 140. Corneal reflexes were present, and pupils were equal, slightly constricted, and sluggishly reactive to light. Except for decreased deep tendon reflexes, the remainder of the physical examination was unremarkable. Oxygen was administered, and within four hours, the child was awake and alert. On arrival the mother was comatose and suffering from generalized convulsions. The pupils were equal, slightly dilated, and slightly reactive to light. Vital signs were as follows: blood pressure, 100/80 m m Fig; pulse, 110; temperature, 36.5 C; and respirations, 25 to 30 with periods of apnea lasting for 15 seconds. It was during apnea t h a t c o n v u l s i o n s i n v o l v i n g mainly the arms were noted. Auscultation of the chest revealed vesicular breath sounds and tales. Endotracheal intubation was performed, and respiratory assistance using 40% oxygen was given. Convulsions were controlled with diazepam. Within four hours the patient was markedly improved, w i t h a blood pressure of 120/70 m m Hg, pulse of 90, and normal respirations. It is assumed that she regained consciousness, although this was not noted specifically. Kingston and Saxena s reported the case of a 20-year-old woman who injected 12 m L T-61 ® intramuscularly and presented to an ED comatose, seizing, and in respiratory arrest. She recovered quickly after respiratory support and resuscitative measures. Patient 3 did not inject, but ingested, both T-61 e and a pentobarbital solution. No a t t e m p t was made to identify embutramide, mebezonium, or tetracaine in biological fluids. It is not possible to completely separate the effects of pentobarbital, embutramide, and transient cerebral hypoxia. Pentobarbital would not be expected to produce a significant neurological deficit two to three days after admission considering that the original serum pentobarbital concentration was only 6.1 v~g/mL. Cavaliere's two patients who were injected with T-61 ®4 and the 20-year-old woman reported by Kingston and Saxena s were both markedly improved within four hours, making it difficult to attribute a neurological deficit of several days to Annals of Emergency Medicine
the T-61. ® Anesthetic doses of embutramide in the dog last about 45 minutes. The prolonged neurological recovery in our patient was most likely due to slow recovery from cerebral hypoxia that resulted from respiratory depression and/or hypotension induced by T-61® and pentobarbital. The curare-like drug m e b e z o n i u m is not well absorbed from the GI tract, making respiratory failure from skeletal muscle weakness or paralysis unlikely. The etiology of the seizures noted in two of the previously reported cases of T-61 ® poisoning is not clear. Although toxic doses of tetracaine may induce seizures, hypoxia m a y have played a major role.
Treatment The treatment of pentobarbital poisoning consists mainly of supportive care. If the pentobarbital solution is ingested, gastric lavage and the administration of activated charcoal should be undertaken. In massive overdoses in which the patient continues to deteriorate in spite of supportive care, charcoal hemoperfusion may be effective.6 An alkaline diuresis does not enhance the elimination of pentobarbital. 6 Although adequate experience in treating poisoning with T-61~ is lacking, it seems that supportive care is the mainstay of therapy. Seizures have not been difficult to control with adequate oxygenation and diazepam. If musculoskeletal paralysis is present, it can be reversed by such anticholinesterase agents as pyridostigmine. Embutramide itself, however, can produce a respiratory arrest f r o m profound CNS depression. Decontamination of the GI tract with gastric lavage and activated charcoal also would be reasonable following the oral ingestion of T-61®. Our experience, along with reports in the medical literature, indicate that most persons who a t t e m p t suicide with veterinary euthanasia agents are employed in the field of veterinary medicine. SUMMARY When confronted with a comatose patient who has access to veterinary preparations, the emergency physician should consider the possibility that a veterinary euthanasia agent has been used in a suicide attempt. The most commonly used pharmaceutical 15:8 August 1986
agents, p e n t o b a r b i t a l s o l u t i o n s and T-61 ®, can cause rapid and profound C N S d e p r e s s i o n , r e s p i r a t o r y arrest, and cardiovascular collapse. Because no specific a n t i d o t e exists for these agents, supportive care appears to be the m a i n s t a y of therapy.
REFERENCES 1. Lumb W~, Doshi K, Scott RF: A comparative study of T-61 and pentobarbital for euthanasia of dogs. JAVMA 1978; 172:149-152. 2. Clark MA, Jones JW: Suicide by intravenous i n j e c t i o n of a v e t e r i n a r y euthanasia agent: Report of a case and toxicologic studies. J Forensic Sci 1979; 24:762-767. 3. Poklis A, Hameli AZ: Two unusual barbiturate deaths. Arch Toxicol 1975; 34:77-80.
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4. Cavaliere U, Andreano C, Raducci B, et al: Intossicazione da T 61 (Tanax). Minerva Anestesiol 1982;48:861-864. 5. Kingston RL, Saxena K: Intentional poisoning by injection of veterinary euthanasia drug (abstract). Clin Toxicol 1979;15:492. 6. Winchester IF: Barbiturates (including primidone), in Haddad LM, Winchester JF (eds): Poisoning and Drug Overdose, ed 1. Philadelphia, WB Saunders Co, 1983, pp 413-424. 7. Harvey SC: Hypnotics and sedatives, in Gilman AG, Goodman LS, Gilman A (eds): The Pharmacological Basis of Therapeutics, ed 6. New York, Macmillan Publishing Co, 1980, pp 339-375. 8. Glasgow AM, Boickx RL, Miller MK, et al: Hyperosmolality in small infants due to p r o p y l e n e glycol. Pediatrics 1983; 72:353-355. 9. Martin G, Finberg L: Propylene glycol:
Annals of Emergency Medicine
A potentially toxic vehicle in liquid dosage form. I Pediatr 1970;77:877-878. 10. Cate JC, Hedrick R: Propylene glycol intoxication and lactic acidosis (letter). N Engl l Med 1980;303:1237. 11. Arulanantham K, Genel M: Central nervous system toxicity associated with ingestion of propylene glycol. / Pediatr 1978;93:515-516. 12. Potter BJ: Haemoglobinuria caused by propylene glycol in sheep. Brit l Pharmacol 1958;13:385-389. 13. Product information supplied in personal c o m m u n i c a t i o n by RK Muser, DVM, Hoechst-Roussel Agri-Vet Company, 1985. 14. Ritchie JM, Greene NM: Local anesthetics, in Gilman AG, Goodman LS, Gilman A leds): The Pharmacological Basis of Therapeutics, ed 6. New York, M a c m i l l a n P u b l i s h i n g Co, 1980, pp 300-320.
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