Abstract 2505: Hydroxocobalamin and Epinephrine Improve Survival in a Swine Model of Cyanide-Induced Cardiac Arrest: A Randomized Trial
Introduction: Hydroxocobalamin (HOCB) is a cyanide (CN) antidote, but it has not been studied in CN-induced cardiac arrest. In addition a clinically relevant model for drug or chemical induced cardiac arrest has not been described.
Hypothesis: Our primary hypothesis was that HOCB will improve survival compared to controls in a CN-induced cardiac arrest swine model. Our secondary outcomes were improvement of blood pressure, lactate, and coronary perfusion pressure with HOCB compared to epinephrine (EPI).
Methods: 45 swine (38 – 42 kg) were intubated, anesthetized, and instrumented (continuous arterial and right atrial pressure monitoring with Millar catheters) and then cyanide was infused (0.2 mg/kg/min) until cardiac arrest (MAP <30 mm Hg). Animals were randomly assigned to intravenous bolus of HOCB (150 mg/kg), EPI (0.02 mg/kg), or saline bolus (control). CPR was performed with a chest compression device (Thumper) and animals were monitored for 60 min after cardiac arrest. Vasopressor infusion (epinephrine 0.1 mcg/kg/min) was used in all arms after ROSC for SBP <90 mm Hg. Forty-five animals were needed for a power of 80% (alpha 0.05). RMANCOVA, chi-square, and post hoc t-test were used to determine significance.
Results: Baseline weight, time to arrest, and cyanide dose at arrest (5.07 mg/kg±0.364 SEM, 4.32 mg/kg±0.257, 4.29±0.314 mg/kg) were similar. All (15) animals in the control group, 4/15 in the HOCB group, and 4/15 in the EPI group died during the study (p<0.001). ROSC at 5 min and 10 min was similar in treatment groups (p >0.9). Vasopressor infusion after ROSC was required for hypotension in 2/11 HOCB animals and in 11/11 EPI animals (p<0.001). At 2 and 4 min after arrest, coronary perfusion pressures were greater than 15 mm Hg in treatment groups. At arrest, mean serum cyanide (4.26, 3.88, 4.1 mcg/ml, p=0.71) and lactate levels (7.5, 6.86, 7.07 mmol/L, p=0.69) were similar in all groups. At 60 min, mean serum lactate (4.9 vs. 12.1 and 14.9 mmol/L, p<0.0001) and pH (7.34 vs. 7.153 and 7.154, p<0.0001) improved in the HOCB group. Serial serum CN levels in the HOCB group were lower than control and EPI groups after arrest until study end (p<0.004).
Conclusions: HOCB and EPI both improved survival compared to controls in this swine model of cyanide induced cardiac arrest.