Homicide with intramuscular cyanide injection: a case report

Abstract Cyanide poisoning most commonly occurs from smoke inhalation, less commonly by oral ingestion for suicide or homicide. There are rare cases of intravenous or subcutaneous parenteral cyanide. We report a fatal case of intramuscular cyanide used as a homicidal agent. A 35-year-old female was assaulted and injected with an unknown substance in her left buttock using a syringe. She was unresponsive at ED arrival and underwent immediate endotracheal intubation. After near normal vital signs at arrival (BP 130/83 mmHg, HR 102 bpm), she rapidly became hypotensive and bradycardic with worsening acidosis (pH 6.95, lactate 7.7 mmol/L). Despite vasopressors, hydroxocobalamin, and sodium thiosulfate, she succumbed. Plasma cyanide concentrations from blood drawn 1 and 4 h post exposure were both in the lethal range (3.4 and 4.1 mg/L, respectively). Our case demonstrates that intramuscular injection can result in fatal cyanide poisoning, resulting in rapid absorption, severe toxicity, and death.


Introduction
Cyanide poisoning most commonly occurs from smoke inhalation, less commonly by oral ingestion for suicide or homicide. There are rare cases of intravenous or subcutaneous parenteral cyanide [1][2][3]. In accordance with the CARE guideline (https://www. care-statement.org), we present a completed homicide by intramuscular injection of cyanide.

Case report
An assailant jumped out of the bushes and injected a 35-year-old female in her left buttock using a syringe as she was walking from her car to her front door. She immediately summoned her mother from inside the house and called 911. She complained of pain and numbness at the site of injection. The patient was awake and talking when emergency medical services arrived on the scene. No prehospital treatment was given.
On arrival to the emergency department one hour after injection, the patient was unresponsive and flaccid with pupils dilated to 7 mm. Given low Glasgow Coma Scale and concerns for airway protection, she underwent immediate endotracheal intubation and mechanical ventilation. Initial assessment revealed a BP 130/83 mmHg and HR 102 bpm, which rapidly deteriorated two hours later to SBP 72 mmHg and HR in the 40 s bpm. Subsequent laboratory studies revealed a blood pH of 6.95 and serum lactate of 7.7 mmol/L. She received epinephrine boluses to treat hemodynamic instability. Three hours after the injection, with no significant clinical improvement, consultation with a medical toxicologist via poison center raised concern for cyanide toxicity. Hydroxocobalamin 5 g and sodium thiosulfate 12.5 g were administered intravenously, with subsequent improvement of blood pH to 7.37 and lactate to 3.3 mmol/L. The patient also received norepinephrine at 20 mcg/min and vasopressin at 0.4 units/min IV to maintain blood pressure. The following day the patient remained unresponsive and absence of cerebral perfusion on nuclear medicine scan confirmed brain death. A post-mortem exam revealed hypoxic encephalopathy and cerebral edema with bilateral uncal herniation.
Blood cyanide concentrations obtained approximately one-hour post-exposure was 3.4 mcg/L and four-hours post-exposure from initial presentation to the emergency department was 4.1 mcg/L (reference range cyanide <0.2 mcg/mL). Cyanide was analyzed using high performance liquid chromatography/tandem mass spectroscopy (HPLC-MS/MS) by National Medical Services on autopsy. For reference, cyanide concentrations >2.5 mcg/mL may cause coma and respiratory depression while cyanide concentrations >3 mcg/mL are generally fatal [4]. Additionally, comprehensive toxicology screening using GC/MS for a large library of pharmaceuticals and drugs of abuse revealed only caffeine.
The assailant was later identified as a former boyfriend of the victim. The incident was captured on surveillance video which was installed because the assailant had recently broken into her home. From the subsequent news report, it was reported that he ordered an antique stainless-steel syringe ( Figure 1) and cyanide on the internet. It is unclear what form of cyanide was ordered or the materials that were used to solubilize the cyanide. The contents of syringe were never analyzed. The assailant was found guilty of first-degree murder and received a life sentence in prison.

Discussion
Injection of solubilized cyanide appears to be very rare, with fatalities reported following intravenous and subcutaneous exposures [1][2][3]. The pharmacokinetics of cyanide following intramuscular administration are unknown. In our case, intramuscular injection of cyanide likely resulted in rapid and continued absorption and severe toxicity. This would explain the rising cyanide concentration despite antidotal therapy.
Hydroxocobalamin use was delayed due to multiple factors. The patient arrived in extremis without a clear history to guide the treating physicians. Also, the clinical suspicion for cyanide poisoning was not apparent until acidemia, elevated lactate and hypotension were apparent. As in this case, clinical presentation, blood pH, and serum lactate may guide diagnosis and treatment of cyanide poisoning since blood cyanide concentrations are not readily available.
Cyanide is a potent inhibitor of multiple enzymes including the a 3 portion of cytochrome oxidase producing intracellular hypoxia [5]. This leads to inhibition of cellular respiration resulting in elevated lactate concentrations [5]. Initial signs and symptoms may be non-specific, moderate toxicity may include syncope, hypotension, dysrhythmias, seizures, and coma [6]. Severe cyanide exposures result in rapid unconsciousness, shock, and severe lactic acidosis [6]. Laboratory studies often reveal a high anion gap metabolic acidosis with an elevated serum lactate, often greater than 8 mmol/L [6]. In this case, absorption was likely slower secondary to route of administration which could have delayed cardiovascular toxicity.

Conclusion
Intramuscular injection of cyanide resulted in rapid and continued absorption with severe toxicity. Serial cyanide concentrations demonstrated continuing absorption at four hours post-injection.

Disclosure statement
No potential conflict of interest was reported by the authors.

Funding
The author(s) reported there is no funding associated with the work featured in this article.