Protective effect of stroma-free methemoglobin during cyanide poisoning in dogs

Abstract

Background: During fire exposure, cyanide toxicity can block aerobic metabolism. Oxygen and sodium thiosulfate are accepted therapy. However, nitrite-induced methemoglobinemia, which avidly binds cyanide, decreases oxygen-carrying capacity that is already reduced by the presence of carboxyhemoglobin (inhalation of carbon monoxide in smoke). This study tested whether exogenous stroma-free methemoglobin (SFmetHb) can prevent depression of hemodynamics and metabolism during canine cyanide poisoning. Methods: In 10 dogs (weighing 18.8 ± 3.5 kg) anesthetized with chloralose-urethane and mechanically ventilated with air, baseline hemodynamic and metabolic measurements were made. Then, 137 ± 31 ml of 12 g% SFmetHb was infused into five dogs (SFmetHb group). Finally, the SFmetHb group and the control group (n = 5, no SFmetHb) received an intravenous potassium cyanide infusion (0.072 mg · kg-1 · min-1) for 20 min. Oxygen consumption (V̇(O2)) was measured with a Datex Deltatrac (Datex Instruments, Helsinki, Finland) metabolic monitor and cardiac output (Q̇T) was measured by pulmonary artery thermodilution. Results: From baseline to cyanide infusion in the control group, Q̇T decreased significantly (p < 0.05) from 2.9 ± 0.8 to1.5 ± 0.4 1/min, mixed venous P(CO2) (Pv̄(CO2)) tended to decrease from 35 ± 4 to 23 ± 2 mmHg, Pv̄(O2) increased from 43 ± 4 to 62 ± 8 mmHg, V̇(O2) decreased from 93 ± 8 to 64 ± 19 ml/min, and lactate increased from 2.3 ± 0.5 to 7.1 ± 0.7 mM. In the SFmetHb group, cyanide infusion did not significantly change these variables. From baseline to infused cyanide, the increases in blood cyanide (4.8 ± 1.0 to 452 ± 97 μM) and plasma thiocyanate cyanide (18 ± 5 to 65 ± 22 μM) in the SFmetHb group were significantly greater than those increases in the control group. SFmetHb itself caused no physiologic changes, except small decreases in heart rate and Pv̄(O2). Peak SFmetHb reached 7.7 ± 1.0% of total hemoglobin. Conclusions: Prophylactic intravenous SFmetHb preserved cardiovascular and metabolic function in dogs exposed to significant intravenous cyanide. Blood concentrations of cyanide, and its metabolite, thiocyanate, revealed that SFmetHb trapped significant cyanide in blood before tissue penetration.