Hydroxocobalamin and sodium thiosulfate versus sodium nitrite and sodium thiosulfate in the treatment of acute cyanide toxicity in a swine (Sus scrofa) model.
OBJECTIVE
Cyanide can cause severe hypotension with acute toxicity. To our knowledge, no study has directly compared hydroxocobalamin and sodium nitrite with sodium thiosulfate in an acute cyanide toxicity model. Our objective is to compare the return to baseline of mean arterial blood pressure between 2 groups of swine with acute cyanide toxicity and treated with hydroxocobalamin with sodium thiosulfate or sodium nitrite with sodium thiosulfate.


METHODS
Twenty-four swine were intubated, anesthetized, and instrumented (continuous arterial and cardiac output monitoring) and then intoxicated with a continuous cyanide infusion until severe hypotension. The animals were divided into 2 arms of 12 each and then randomly assigned to intravenous hydroxocobalamin (150 mg/kg)+sodium thiosulfate (413 mg/kg) or sodium nitrite (10 mg/kg)+sodium thiosulfate (413 mg/kg) and monitored for 40 minutes after start of antidotal infusion. Twenty animals were needed for 80% power to detect a significant difference in outcomes (alpha 0.05). Repeated measures of analysis of covariance and post hoc t test were used for determining significance.


RESULTS
Baseline mean weights, time to hypotension (31 minutes 3 seconds versus 28 minutes 6 seconds), and cyanide dose at hypotension (5.6 versus 5.9 mg/kg) were similar. One animal in the hydroxocobalamin group and 2 animals in the sodium nitrite group died during antidote infusion and were excluded from analysis. Hydroxocobalamin resulted in a faster return to baseline mean arterial pressure, with improvement beginning at 5 minutes and lasting through the conclusion of the study (P<.05). No statistically significant difference was detected between groups for cardiac output, pulse rate, systemic vascular resistance, or mortality at 40 minutes post intoxication. Mean cyanide blood levels (4.03 versus 4.05 microg/mL) and lactate levels (peak 7.9 versus 8.1 mmol/L) at hypotension were similar. Lactate levels (5.1 versus 4.48 mmol/L), pH (7.40 versus 7.37), and base excess (-0.75 versus 1.27) at 40 minutes were also similar.


CONCLUSIONS
Hydroxocobalamin with sodium thiosulfate led to a faster return to baseline mean arterial pressure compared with sodium nitrite with sodium thiosulfate; however, there was no difference between the antidote combinations in mortality, serum acidosis, or serum lactate.
Bebarta
Vikhyat S
VS
Medical Toxicology, University of Texas Health Sciences Center, San Antonio, TX, USA. vikbebarta@yahoo.com
Tanen
David A
DA
Lairet
Julio
J
Dixon
Patricia S
PS
Valtier
Sandra
S
Bush
Anneke
A
D000138:Acidosis / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003486:Cyanides / Q000506:poisoning*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006879:Hydroxocobalamin / Q000627:therapeutic use*; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy; D007773:Lactates / Q000097:blood; D008297:Male; D008991:Monitoring, Physiologic; D012977:Sodium Nitrite / Q000627:therapeutic use*; D034421:Sus scrofa; D013885:Thiosulfates / Q000627:therapeutic use*; D013997:Time Factors
D000931:Antidotes; D003486:Cyanides; D007773:Lactates; D013885:Thiosulfates; C017717:sodium thiosulfate; D012977:Sodium Nitrite; D006879:Hydroxocobalamin