While working the overnight shift a child is brought in to your emergency department from a house fire. His burns are minor, but he was found in the house and likely had a significant smoke inhalation. The paramedics have started oxygen therapy, and as an astute emergency physician you add a blood gas with cooximetry, lactate and cyanide level to your initial orders. You are preparing to administer the CYANOKIT (hydroxocobalamin) but you pause for a moment to ask, “Should I be sending additional labs before I give this medications? Will this affect management in the next 24 hours? Are there other options?”
Cyanide Toxicity Treatments
Cyanide toxicity is a rare but dangerous exposure that can rapidly result in cardiac arrest. In Western countries, emergency physicians primarily see cyanide exposure in smoke inhalation patients, however there continue to be reported cases of cyanide toxicity in suicide/homicide victims and concern for cyanide as a chemical terrorism weapon.1,2 Worldwide there are multiple therapies used for cyanide poisoning including nitrites, thiosulfates, hydroxocobalamin and 4-dimethylaminophenol (4-DMAP).3,4 Historically, in the United States the standard of care for the treatment of suspected cyanide toxicity had been the Cyanide Antidote Kit (amyl nitrite, sodium nitrite and sodium thiosulfate).5 However, in 2006 the CYANOKIT (hydroxocobalamin) was approved for use in the United States and has largely replaced the Cyanide Antidote Kit in the emergency setting.6 Studies have demonstrated the superiority of hydroxocobalamin compared to sodium nitrite and sodium thiosulfate in overall survival, lack of hypotensive effects and lack of methemoglobinemia. 4,7,8 The reported adverse events associated with hydroxocobalamin include chromaturia, erythematous rash, and elevated heart rate and elevated blood pressure. 8-10
Considerations with Hydroxocobalamin
With the widespread use of hydroxocobalamin, there exist several clinical care considerations that the emergency physician must keep in mind while administering this medication. First, multiple laboratory values depend on colorimetric methods, which are affected by the plasma discoloration caused by hydroxocobalamin. Though dependent on the analyzer, hydroxocobalamin can affect the reported values of multiple labs including aspartate aminontransferase (AST), alanine aminotransferase (ALT), bilirubin, albumin, alkaline phosphatase cholesterol, triglycerides, total protein, creatinine, magnesium, phosphate, glucose, creatine kinase, lactate dehydrogenase, and hemoglobin.10 Further, cooximetry measurements of carboxyhemoglobin, methemoglobin and oxyhemoglobin are affected by the plasma discoloration, most notably resulting in falsely elevated carbon monoxide levels.11 The second consideration is the need for dialysis, as the plasma discoloration can trigger the photodetector in a hemodialysis machine to spuriously detect a “blood Leak.”12 Given the often profound metabolic acidosis associated with cyanide toxicity that can require dialysis, the nephrology team should be made aware of this effect prior to the initiation of dialysis.
Future Therapies for Cyanide Toxicity
In recent years, cobinamide has been proposed as a therapy for cyanide toxicity. It carries with it the benefit of binding two molecules of cyanide with a higher affinity than hydroxocobalamin, and in mouse models has demonstrated a more rapid and complete reversal of the toxic effects of cyanide.13 The benefit of cobinamide has not been borne out in a swine model, however there is speculation that this was related to the dosing of cobinamide vs. hydroxocobalamin and further investigation is needed.14,15 Currently, an intramuscular version of cobalimide combined with sodium nitrite, nitrocobinamide, has shown promise in animal models and is in the process of FDA approval for human trials.16 Once approved, this medication would be easily administered and potentially be more efficacious than intravenous hydroxocobalamin.17
Hydroxocobalamin is an effective and safe medication to administer in cyanide poisoning. It should not be delayed when there is clinical suspicion for exposure, however consider drawing additional laboratory studies that may be useful in the next several hours and warning your pediatric intensivist that future lab values and dialysis may be affected by this medication. And be on the look-out for new therapies that are right around the corner.
Jessica Wall, MD, MPH, NRP
Pediatric Emergency Medicine Fellow
Children’s Hospital of Philadelphia
- Eckstein M. Cyanide as a chemical terrorism weapon. JEMS. April 2014:22–31.
- Dart RC. Hydroxocobalamin for Acute Cyanide Poisoning: New Data from Preclinical and Clinical Studies; New Results from the Prehospital Emergency Setting. Clinical Toxicology. 2008;44(sup1):1–3. doi:10.1080/15563650600811607.
- Nagler J, Provoost RA, Parizel G. Hydrogen cyanide poisoning: treatment with cobalt EDTA. J Occup Med. 1978;20(6):414–416.
- Hall AH, Dart R, Bogdan G. Sodium Thiosulfate or Hydroxocobalamin for the Empiric Treatment of Cyanide Poisoning? Annals of Emergency medicine. 2007;49(6):806–813. doi:10.1016/j.annemergmed.2006.09.021.
- ABO Pharmaceuticals. http://www.abopharmaceuticals.com/products/cyanide-antidote-kits/. Accessed April 24, 2016.
- Cyanokit. http://www.cyanokit.com/faqs. Accessed April 24, 2016.
- Bebarta VS, Pitotti RL, Dixon P, Lairet JR, Bush A, Tanen DA. Hydroxocobalamin Versus Sodium Thiosulfate for the Treatment of Acute Cyanide Toxicity in a Swine (Sus scrofa) Model. YMEM. 2012;59(6):532–539. doi:10.1016/j.annemergmed.2012.01.022.
- Borron SW, Baud FJ, Mégarbane B, Bismuth C. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. The American journal of emergency medicine. 2007;25(5):551–558. doi:10.1016/j.ajem.2006.10.010.
- Borron SW, Baud FJ, Barriot P, Imbert M, Bismuth C. Prospective Study of Hydroxocobalamin for Acute Cyanide Poisoning in Smoke Inhalation. Annals of Emergency medicine. 2007;49(6):794–801.e2. doi:10.1016/j.annemergmed.2007.01.026.
- Cyanokit Package Insert. Meridian Medical Technologies http://www.cyanokit.com/files/Single_5-g_Vial_PI.pdf.
- Lee J, Mukai D, Kreuter K, Mahon S, Tromberg B, Brenner M. Potential Interference by Hydroxocobalamin on Cooximetry Hemoglobin Measurements During Cyanide and Smoke Inhalation Treatments. Annals of Emergency medicine. 2007;49(6):802–805. doi:10.1016/j.annemergmed.2006.11.016.
- Sutter M, Tereshchenko N, Rafii R, Daubert GP. Hemodialysis Complications of Hydroxocobalamin: A Case Report. J Med Toxicol. 2010;6(2):165–167. doi:10.1007/s13181-010-0067-9.
- Brenner M, Mahon SB, Lee J, et al. Comparison of cobinamide to hydroxocobalamin in reversing cyanide physiologic effects in rabbits using diffuse optical spectroscopy monitoring. J Biomed Opt. 2010;15(1):017001. doi:10.1117/1.3290816.
- Bebarta VS, Tanen DA, Boudreau S, et al. Intravenous cobinamide versus hydroxocobalamin for acute treatment of severe cyanide poisoning in a swine (Sus scrofa) model. Ann Emerg Med. 2014;64(6):612–619. doi:10.1016/j.annemergmed.2014.02.009.
- Schapira K, Kessler BD, Howland MA, Su M. Intravenous cobinamide versus hydroxocobalamin for acute treatment of severe cyanide poisoning in a swine (Sus scrofa) model. Ann Emerg Med. 2015;65(2):234–235. doi:10.1016/j.annemergmed.2014.10.013.
- Chan A, Jiang J, Fridman A, et al. Nitrocobinamide, a New Cyanide Antidote That Can Be Administered by Intramuscular Injection. J Med Chem. 2015;58(4):1750–1759. doi:10.1021/jm501565k.
- Petrikovics I, Budai M, Kovacs K, Thompson DE. Past, present and future of cyanide antagonism research: From the early remedies to the current therapies. World J Methodol. 2015;5(2):88–100. doi:10.5662/wjm.v5.i2.88.