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Early Clinical Trials Suggests Hydroxocobalamin Beneficial for Hemorrhagic Shock

Issue 5 and Volume 40.

Avoiding Shock

Bebarta VS, Garrett N, Boudreau S, et al. A prospective, randomized trial of intravenous hydroxocobalamin versus whole blood transfusion compared to no treatment for class III hemorrhagic shock resuscitation in a prehospital swine model. Acad Emerg Med. 2015;22(3):321–330.

Hypovolemia and shock in trauma remains one of the leading causes of death from traumatic injuries. To combat hypovolemia and hemorrhage, we’ve seen repeated attempts at synthetic blood replacements and certain services carrying actual blood products. Unfortunately, synthetics have had mixed results and blood itself is very difficult to stock. With that in mind, researchers from the San Antonio Military Medical Center are considering an alternative use for a medication that may already be in some of our ambulances.

Hydroxocobalamin, also known as Cyanokit, was approved for use in the U.S. as a treatment for cyanide poisoning in 2007. Also a member of the vitamin B12 family, hydroxocobalamin’s effect on nitric oxide (NO) has been linked to improved blood pressure in previous studies. NO is a signaling molecule in the body that can be used by the vasculature and cardiovascular system to cause vasodilation and decrease blood pressure. Hydroxocobalamin scavenges for NO in the bloodstream, leading to an increase in blood pressure and systemic vascular resistance.

Study Set-up: The authors studied the effects of hydroxocobalamin in pigs with significant blood loss. Thirty swine were sedated, intubated and had invasive blood pressure monitoring lines placed before having 20 mL/kg of blood removed over a 20-minute period to create class 3 shock. The pigs were then randomly assigned to three groups–10 pigs received 150 mg/kg of hydroxocobalamin, 10 received 500 mL of whole blood (positive control) and 10 received no treatment (negative control). All treatments were administered five minutes after blood removal. This is important for study purposes because it shows a comparison between a medically accepted treatment, the new therapy and no intervention at all.

Five minutes after the administration of treatments, animals in the no treatment group had an average heart rate of 129.5 bpm, compared to 95.2 bpm in the whole blood group and 97.3 bpm in the hydroxocobalamin group. Serum lactate was 1.4 mmol/L in both the hydroxocobalamin group and the whole blood group, compared to 3.1 mmol/L in pigs receiving no treatment. Systolic blood pressures in the two treatment groups were 15–20 mmHg higher as well.

At 60 minutes from time of hemorrhage–55 minutes from administration of treatments–serum lactate levels in the no treatment group averaged 3.8 mmol/L, compared to 1.1 mmol/L in the whole blood group and 1.4 mmol/L in the hydroxocobalamin group. Systolic blood pressures averaged 80.9 mmHg in the whole blood group, 75.1 mmHg in the hydroxocobalamin group and 55.3 mmHg in the no treatment group. All results listed were statistically significant.

Discussion: Hydroxocobalamin doesn’t stop or control bleeding; its use in trauma would be limited to hypotensive states when hemorrhage has been stopped, or relative hypovolemia is due to a loss of vascular tone (larger container but same amount of fluid). With the exception of a dramatically increased systemic vascular resistance in the hydroxocobalamin group, the administration of hydroxocobalamin closely mirrored the effects of whole blood administration in terms of effects on vital signs. Hydroxocobalamin also didn’t affect coagulation pathways negatively. The other interesting thing is that the administration of it bought researchers about 60 minutes of hemodynamic stability, introducing the idea that this medication could be helpful in rural areas or combat zones to buy time before the administration of blood products and surgical intervention.

We’d like to thank Bebarta and his associates for such a well-designed animal study. This type of research is an essential precursor to human trials. We must weigh the risks and benefits of this therapy before trying it on humans. The cardiovascular physiology of pigs is quite similar to humans and this type of laboratory setting allows researchers to carefully control variables.

What does this all mean? Should we all start stocking hydroxocobalamin in our ambulances tomorrow? The answer is absolutely not (yet). This is early in the research process. The fact of the matter is that hydroxocobalamin is expensive, has a short half-life, is useful only in certain types of shock where bleeding is controlled, and this is just one animal study. It would be prudent to wait for at least one, if not several, prehospital randomized controlled and double-blinded trials before recommending its use.  

Bottom Line

What we know: Hypotension and hypovolemia in trauma can be fatal when not rapidly addressed in the prehospital setting.

What this study adds: The possibility that the use of hydroxocobalamin, a medication that already has some practical uses in the EMS world, may be a viable option for traumatic hypotension.