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Introduction

  1. Pharmacology. Hydroxocobalamin is an analog of vitamin B12 that is used for the treatment of vitamin B12 deficiency syndromes in small doses and as an antidote for human cyanide poisoning in large doses. Hydroxocobalamin rapidly exchanges its hydroxyl group with free cyanide to produce stable cyanocobalamin. With a molar binding ratio of hydroxocobalamin to cyanide of 1:1, 5 g of hydroxocobalamin will neutralize 97 mg of cyanide. Hydroxocobalamin also scavenges nitric oxide and hydrogen sulfide, mediators of vasodilation. When administered to patients with cyanide poisoning, it rapidly improves the heart rate, systolic blood pressure, and acidemia. Early administration prior to cardiopulmonary arrest is associated with better outcomes. In healthy volunteers, administration of 5 g and 10 g of IV hydroxocobalamin resulted in average plasma half-life values for cobalamin compounds of 26 and 31 hours, respectively. If IV access is unavailable, consider intraosseous administration. Oral and intranasal absorption is poor, and large volumes (5 g/200 mL) preclude IM administration.
  2. Indications
    1. Treatment of acute cyanide poisoning or symptomatic patients suspected to be at high risk for cyanide poisoning (eg, smoke inhalation victims).
    2. Prophylaxis or treatment of cyanide poisoning during nitroprusside infusion (off label).
    3. Some animal studies suggest a benefit in acute hydrogen sulfide poisoning.
    4. Refractory vasoplegia unresponsive to standard treatments (off label).
  3. Contraindications. Use caution when managing patients with known hypersensitivity to hydroxocobalamin or cyanocobalamin and consider alternative treatments.
  4. Adverse effects
    1. Adverse reactions in healthy volunteers include chromaturia (red-colored urine) in 100%, erythema in 94-100%, rash in 20-44%, increased blood pressure in 18-28%, nausea in 6-11%, headache in 6-33%, decreased lymphocyte percentage in 8-17%, infusion site reaction in 6-39%, and oxalate crystalluria in 56-61%. Although red-colored body fluids usually normalize within 2-7 days, erythema can last up to 2 weeks and chromaturia up to 35 days. A self-limiting acneiform rash may occur 7-28 days after infusion.
    2. Oxalate crystal deposition in the kidney has been reported in some burn patients receiving hydroxocobalamin for smoke inhalation with suspected cyanide poisoning. Monitor for crystalluria and renal dysfunction.
    3. Allergic reactions have not been reported with acute intravenous therapy for cyanide poisoning. However, allergic reactions have been reported in patients using chronic IM therapy and in healthy volunteers unexposed to cyanide who were given IV hydroxocobalamin while participating in clinical safety trials.
    4. Use in pregnancy. FDA Category C. The acute, short-term use of hydroxocobalamin for a seriously symptomatic, cyanide-poisoned patient is preferred over nitrite administration. Cobalamin compounds cross the placenta and have been detected in human newborn urine samples.
  5. Drug or laboratory interactions
    1. Laboratory tests. Coloration of bodily fluids caused by cobalamins can interfere with laboratory tests ranging from 12 to 48 hours for blood and serum and up to 8 days for urine. Sampling and storing specimens before antidote administration is recommended, if possible. Test results that are commonly affected include:
      1. Falsely decreased ALT and amylase.
      2. Falsely increased AST, serum creatinine, glucose, alkaline phosphatase, albumin, total protein, bilirubin, triglycerides, cholesterol, hemoglobin, MCH, MCHC, basophils, and most urine chemistry parameters.
      3. Unpredictable effects for carbon monoxide, lactate, CK, CKMB, and PT/INR.
      4. Currently, interference has not been documented in serum tests for Na, K, Cl, Ca, BUN, and GGT (gamma-glutamyl transferase).
    2. Dialysis machines. Hydroxocobalamin has been reported to falsely trigger the automated blood leak detector in some hemodialysis machines, causing them to shut off.
    3. Administration of hydroxocobalamin should be via a separate IV line from other medications. To date, chemical or physical incompatibility has been documented for diazepam, dobutamine, dopamine, fentanyl, nitroglyerin, pentobarbital, propofol, thiopental, sodium thiosulfate, sodium nitrate, and ascorbic acid.
  6. Dosage and method of administration
    1. Acute cyanide poisoning. Give 5 g (children: 70 mg/kg) by IV infusion over 15 minutes; for severe cases, a second 5-g dose may be infused over 15 minutes to 2 hours if needed.
    2. Off-label uses
      1. Prophylaxis during nitroprusside infusion: Administer 25 mg/h IV.
      2. Vasodilatory shock: Optimal dosing is unknown.