Presently, there are two widely accepted antidotes: sodium thiosulfate and hydroxocobalamin. Here, we present two cases resulting from the same source of cyanide poisoning and the use of both antidotes separately used with differing outcomes. Cyanide has well known adverse effects, some of which are rapidly fatal, documented as early as [ 1 ]. Exposure to cyanide ions can occur through inhalation, skin absorption, and ingestion or even through metabolism.
Most commonly, cyanide is inhaled from the thermal breakdown of synthetic compounds during residential or industrial fires [ 1 , 2 ]. Once internalized, cyanide binds to cytochrome oxidase a 3 , a terminal complex in the electron transport chain [ 3 ].
This process prevents aerobic metabolism, which results in diffuse clinical symptoms such as dizziness, headache, weakness, and tachypnea, with progression to seizures, paralysis, and coma [ 4 , 5 ]. Typically, cyanide toxicity treatment is initiated when there is high clinical suspicion of exposure. There are presently two leading antidote treatments, hydroxocobalamin and sodium thiosulfate, which have been mainly described in case reports and retrospective and prospective studies to demonstrate their functional effectiveness in cyanide poisoning [ 6 , 7 ].
Here, we present two case reports following the same initial cyanide exposure with two distinct antidote treatments. Patient is a year-old male with past medical history of hypertension who presented following cardiac arrest. The patient was found to be unconscious in a metal chrome plating shop for undetermined duration of time near another unconscious male Case 2.
Emergency medical services arrived and found the patient in asystole and started advanced cardiac life support protocol. Intubation occurred on the field. The resuscitation efforts occurred for 45 minutes while the patient was being transported to an outside hospital. Following return to spontaneous circulation, the patient was hypotensive requiring dopamine and norepinephrine.
Due to the work environment, the patient received a cyanide antidote kit sodium thiosulfate Once the patient was hemodynamically stable, he was transported to our hospital for further management. The vital signs were the following: temperature On initial physical exam, pertinent positives include no responsiveness with coarse breaths sounds on ventilator.
White blood cell count was Arterial blood gas included pH 6. Hepatic function panel had total bilirubin 0.
A lactate level of Urine drug screen was positive for cocaine metabolites, benzodiazepines, and cannabinoids. Chest X-ray showed pulmonary edema. Head computed tomography was performed with diffuse cerebral edema, most consistent with anoxic brain injury Figure 1. Brain death protocol was initiated. No neuromuscular or central nervous system medications were administered.
Two neurological examinations showed limited reflexes and failure of the apnea test. The patient was pronounced dead. This patient is a year-old male with a past medical history of spontaneous pneumothorax and urethral stricture who was found unconscious in a metal chrome plating shop for an undetermined duration of time near another unconscious male Case 1.
A bystander discovered the patient and emergency medical services were called. The patient was intubated on the field due to inability to protect airway and decreased mentation. On initial arrival at the emergency department, the patient remained unconscious. Due to the working environment, hydroxocobalamin 5 grams was administered 4 minutes after arrival. On initial physical exam in transfer to the intensive care unit approximately 4 hours after presenting , the patient was awake and responsive to commands.
Pupils were equally round and reactive to light and accommodation with extraocular movements intact. Pulmonary exam had coarse breath sounds on ventilator. Arterial blood gas included pH 7. Urine drug screen was positive for cocaine metabolites. Chest X-ray had mild vascular fullness. Head computed tomography was performed with no acute intracranial abnormality and abnormality of the cervical spine Figure 2.
The patient was given aggressive intravenous fluids. Within 24 hours, the patient was weaned off ventilator settings and extubated. The severe lactic acidosis and metabolic derangements rapidly improved.
On the third day, the patient on exam was completely asymptomatic with no residual neurological findings. The laboratory electrolytes were within normal limits. The patient was discharged home. Cyanide has been observed in toxic exposure for centuries prior to the isolation of the compound [ 6 ].
This substance has many potential sources, most commonly from combustion of silk, wool, and synthetic polymers from residential or industrial fires [ 5 , 8 ]. Cyanide consists of a carbon molecule triple bonded to nitrogen.
This compound is highly reactive to metals such as ferric ions [ 2 ]. Upon absorption, the compound enters the cellular mitochondria and disrupts cytochrome oxidase a 3 by binding to the ferric ion [ 5 ]. By halting the electron transport chain, adenosine triphosphate production is inhibited leading to anaerobic glycolysis [ 5 ].
The absorbed cyanide is primarily metabolized through the liver with an enzyme called rhodanese that catalyzes the conversion of cyanide to thiocyanate. This molecule can be excreted via the kidneys. With large doses of cyanide, this mechanism is overwhelmed largely due to insufficient sulfur donors [ 2 , 5 ]. A high concentration of cyanide exposure causes sudden inhibition of cellular respiration.
Effects can be rapid with possible death resulting within seconds to minutes [ 5 ]. With this inhibition, many diffuse clinical symptoms have been observed including dizziness, headache, weakness, tachypnea, diaphoresis, decreased consciousness, and seizures [ 2 , 5 ].
With no pathognomonic clinical symptom or current rapid cyanide blood test, high clinical suspicion is crucial in the initiation of the cyanide antidote treatments. Antidote therapy remains integral in the rapid therapeutic intervention that has been previously shown to be effective. Currently, there have been multiple treatments that have been largely evaluated by clinical observation and animal studies [ 9 ].
The cyanide antidote kit includes amyl nitrite, sodium nitrite, and sodium thiosulfate [ 5 ]. This combination has been used for decades and was demonstrated in our first case. Amyl nitrite has a rapid onset of action and short half-life. Amyl nitrate primarily works by converting hemoglobin to methemoglobin, which binds to cyanide and allows cytochrome oxidase a 3 to reactivate the electron transport chain [ 5 , 9 ].
Additionally, vasodilation occurs through nitrites which may also provide a protective benefit from cyanide toxicity [ 5 ].
Sodium thiosulfate is given in combination with nitrites and has shown improvement in survival in animal studies [ 9 ].
Additionally, with no clinical trials, the effectiveness has been extrapolated from case reports [ 10 ]. Sodium thiosulfate acts as a sulfur donor in the conversion of cyanide to thiocyanate through rhodanese [ 11 ]. It has poor penetration into the mitochondria, which is the site of action, causing slow onset [ 9 ]. With a short half-life and delay onset, sodium thiosulfate must be given in combination with other therapies [ 5 ]. The primary concern in this administration of the cyanide antidote kit is the side effects, including severe hypotension, methemoglobinemia, and hypersensitivity reactions [ 2 ].
Additionally, although methemoglobin will alleviate the cyanide burden on aerobic metabolism, the resulting methemoglobinemia will decrease the ability of the red blood cells to release oxygen to tissues [ 2 ]. Hydroxocobalamin has been used in treatment of cyanide poisoning for over 30 years, with gradually expanding acceptance of its safety and effectiveness [ 2 ].
Cyanide has a greater affinity to bind with hydroxocobalamin rather than cytochrome oxidase a 3 forming cyanocobalamin [ 2 , 3 ]. This newly formed compound is renally excreted [ 12 ]. The effectiveness has been shown in retrospective and prospective studies. Additionally, animal studies have displayed improved mortality with treatment [ 6 ].
Side effects have been considered more minimal with findings of headaches, hypersensitivity reactions, hypertension, reflex bradycardia, reddening of the skin, and urine discoloration [ 3 , 11 ]. With a history of less severe adverse reactions and acute onset, this cyanide antidote treatment has been gaining acceptance [ 12 ].
The international medical community lacks consensus about the antidote or antidotes with the best risk-benefit ratio. Critical assessment of cyanide antidotes is needed to aid in therapeutic and administrative decisions that will improve care for victims of cyanide poisoning particularly poisoning from enclosed-space fire-smoke inhalation , and enhance readiness for cyanide toxic terrorism and other mass-casualty incidents.
This paper reviews preclinical and clinical data on available cyanide antidotes and considers the profiles of these antidotes relative to properties of a hypothetical ideal cyanide antidote. Each of the antidotes shows evidence of efficacy in animal studies and clinical experience. The data available to date do not suggest obvious differences in efficacy among antidotes, with the exception of a slower onset of action of sodium thiosulfate administered alone than of the other antidotes.
The potential for serious toxicity limits or prevents the use of the Cyanide Antidote Kit, dicobalt edetate, and 4-dimethylaminophenol in prehospital empiric treatment of suspected cyanide poisoning.
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