Playing With Fire - Cyanokit Logistics


My EMT partner and I were hanging around on scene waiting for the funeral home staff to show up on our welfare check gone bad. The medical examiner had departed after performing his preliminary exam, now it was just a waiting game.


---Over the Radios---



*** ALERT RESIDENTIAL STRUCTURE FIRE WITH SOMEONE TRAPPED***.

The funeral home finally shows up just as the call is going out and we pass the scene off promptly and head to the fire.


We arrived on scene to care for a patient who had been pulled from the home by a deputy and police officer. The patient has singed hair, soot in her nose and between her teeth, and is coughing. The patient reports "My throat feels like it got sunburned." Patient is groggy and confused, with a GCS of 12. Further assessment revealed tachycardia, tachypnea, and a WNL SpO2. Our monitor was not capable of recognizing Carbon Monoxide


I did opt for elective intubation to secure a potentially crashing airway, and all goes smoothly. It was my very first RSI and I was thrilled with how it went. I realize that I do not have enough medications to keep a patient down for what potentially could be an hour and a half trip to the city, (thanks to the ongoing winter storm) nor a ventilator. Our critical access hospital did not have the means to care for this type of patient and air transport was not an option due to weather, a Snownado if I recall correctly-probably.


Thinking outside the box, I have my partner call the transfer center and see if one of the ambulances that does the CCT for the Metro area would rendezvous with us half way, confident that I had enough medication to manage for that long.


Once we met with the Metro CCT service, we got the patient swapped over to their ambulance, on the vent, and a report was given. Overall, I felt pretty good about my first RSI and was happy with the solution we came up with to get the patient to definitive care. Then, first question asked after I gave report was, “What time did you administer the Cyanokit?"

My heart sank as I was served a big ole’ dose of humble pie. I will never forget the sinking feeling of missing a HUGE step in this patient's care. Not being super familiar with Cyanide poisoning or the Cyanokit, it made me think about what steps I should have taken with this patient, while trying to remember what was taught in paramedic school over the topic. What management options are available? Would I have even of been able to rapidly determine what was needed, or even known how to do what was needed? Today we are going to answer those questions. We will touch on what Cyanide is and how it affects the body. The Cyanokit including: mechanism of actions, indications, side effects and how to administer the Cyanokit.


The Cyanokit is generally used when there is a high suspicion of Cyanide (CN) poisoning after being trapped in an enclosed area during a fire. The setup to infusion time is about 2-3min and the sooner you administer, the better. Luckily, this CCT service carried it and was able to get it going.....but not without some difficulty.


When do you decide to utilize Cyanokit?

The most common instance of CN poisoning in the US is smoke inhalation from structure fires, followed by suicide attempts and lastly, industrial exposure. CN poisoning can be obtained by inhalation, topical exposure, or ingestion.

In 2013, a nightclub fire in Brazil killed hundreds, up to 150 suspected deaths from CN poisoning, many even after escaping the building. The US sent 140 Cyanokits to aid in the treatment of victims, however, for many it was too late.

Houston Fire was the first in the nation to use a Cyanokit and was able to revive a downed Firefighter after the administration of their first kit. HFD routinely uses the Cyanokits for fireground personnel and patients involved in housefires with great success.



How does Cyanide kill?

CN will bind with Fe3+(Ferric) in the Cytochrome C Oxidase in the Mitochondria, causing an enzyme inhibition and leading to a complex IV failure in the Electron Transport Chain. (ETC)

You likely remember from A&P, the ETC is the energy producing part of cellular respiration and ATP production.


When Complex IV is out of the picture, the cell cannot utilize oxygen as an electron acceptor (Complex V), causing the cells to resort to an anaerobic cellular metabolism.


During anaerobic metabolism, ATP cannot be produced in high quantities, thus cells become energy deficient and rely on the anaerobic state. Increased Lactic Acid levels are also a result in an anaerobic cellular state and you will see a profound High Anion Gap Metabolic Acidosis (HAGMA). When the cells cannot utilize the Oxygen that is attached to the Hemoglobin, the Hemoglobin has no reason to offload the Oxygen.

---What will labs look like?---

***CYANOKIT ADMINISTRATION SHOULD NOT BE DELAYED IF SUSPICION OF CN POISIONING EXISTS, EVEN FOR LABS***

In the field there will be no reason to withhold Cyanokit administration to wait for labs. However, if you do find yourself in a situation where you are caring for a patient with suspected CN poisoning and they have not been treated yet, what labs should you expect to see?

ABG and VBG's will Have a <10% A-V O2 difference, meaning that the PaO2 and the PvO2 will be nearly the same.

pH will be LOW, and your HCO3 will be LOW, after all, we did say it was a HAGMA - the "M" meaning METABOLIC.

If you care to calculate an anion gap with the labs you have, more power to you, you'll likely see a >12 anion gap and a Lactate levels of >10.

Cyanokit: Evolution and Mechanism of Action

Originally there was a CN antidote kit that was mostly used in hospital settings. The Cyanide antidote kit consists of three medications given in sequence: Amyl Nitrite, Sodium Nitrite, and Sodium Thiosulfate. The Amyl Nitrite is given by inhalation for 15 to 30 seconds, while Sodium Nitrite is administered intravenously over three to five minutes. Intravenous Sodium Thiosulfate is administered for about 30 minutes. Now, the frontline treatment around the world is almost exclusively the Cyanokit. There are some instances that other medications will be needed, however, in a pre-hospital setting or acute care phase of a CN poisoning you will likely not see these.


The Cyanokit is much easier to use and consists of 5g of Hydroxocobalamin (a form of vitamin B12) that enables the body to excrete the Cyanide through the urine. Hydroxocobalamin, the active ingredient in Cyanokit, binds with the Cyanide and makes Cyanocobalamin. Cyanocobalamin hangs on to the Cyanide and takes it for a ride all the way to the toilet!


Cyanokit Indications

According to Meridian Medical Technologies, the manufacturer of Cyanokit, patients with any of the following S/S that were in an environment likely to have CN should be treated as if they have CN poisoning until proven otherwise.

The patient I spoke of above, met many of these criteria. This patient did in fact benefit from the administration, and got another infusion at the receiving facility with an overall great outcome.

In the field, we likely will not have means to confirm CN poisoning -(Blood lactate <10 mmol/L) Instead, we will have to suspect exposure based on the high index of suspicion that the contents burning would off gas CN. (Virtually any material that is burned under high temperature and in a low oxygen environment)


Inhalation injury patients can be hard to manage due to airway compromise, CO, CN, and thermal burn injuries. CO and CN are both highly toxic and pose a significant threat when patients are exposed to their own singular compounds, let alone, both simultaneously. Many cardiac monitors' SpO2 sensors are able to differentiate between CO and O2 molecules attached to Hb, thus being able to confirm CO poisoning in the field with a diagnostic tool. Luckily, your basic management of a fire victim will likely resolve the CO exposure and is all you can do in the field.


How to administer Cyanokit

I took a poll on multiple social media platforms asking if providers were confident in when to administer Cyanokit and how to administer the Cyanokit. Out of the 480 responses, (I don’t have a huge following- @tonyhenry2012) about 70 percent of providers voted that they did not feel comfortable with the process of administering a Cyanokit. I understand it is not our most common intervention, but when you do need to perform it, time is critical. Services often shy away from the Cyanokit due to the high price and rather short shelf life, as well as the fact that it is a rather infrequently used medication, however, that doesn’t mean it’s not important.

We’ve covered quite a bit of info about how CN and the Cyanokit works, and that brings us to how to set up and administer.


Set up and administration

Included in the kit you have:

· 1 Vial containing Hydroxocobalamin lyophilized powder

· 1 VENTED IV drip set

· 1 Transfer spike (not a Quicktrach)

· Reference guide

· Package insert

The kit comes all together in a box and looks like this.

If storing the contents of the kit in any way besides the box it comes in, be sure that all the contents of the kit are kept together. It is very easy to lose the transfer spike or the vented tubing that are included.

When opening the box, it may appear as though there is many steps to set up a Cyanokit. If you have had a hospital setting job, you are likely familiar with how Alteplase is reconstituted and administered. The Cyanokit is very similar to set up and should be something that can be rapidly accomplished.

Take the included transfer spike and insert one end into the vial and the other into a bag of NS. Once 200ML of NS is transferred to the vial, or to the fill line, rock and invert the vial for at least 60 seconds to mix adequately. -DO NOT SHAKE- The Hydroxocobalamin is stored in a lyophilized powder form, which increases its shelf life to 36 months. After Reconstitution, the product lasts for 6 hours.


After the product is adequately mixed you can attach the included vented tubing and prime the dripset. The finished product will be bright red and should be infused over 15 min for adults. Refer to your local guidelines for peds/K9 dosing.

You may administer another dose with a max dose of 10g. According to the manufacturer, a physician should be consulted prior to 2nd dose.


Side effects and considerations

According to Meridian, they do not list any specific contraindications for this product, only a consideration of “Known allergy to Hydroxocobalamin” and recommends managing symptoms of a reaction during and after administration if no other alternative therapies are available.

It is recommended that you administer Cyanokit through a designated line, as there are multiple incompatibilities with other drugs.

18 percent of patients had an increase of blood pressure >180 systolic after a 5g administration, and 28 percent after 10g were reported during medication studies. Other possible side effects include: red urine, dry throat, headache, infusion site reaction, eye redness, cardiac rhythm disturbance, and flash pulmonary edema. Be sure to monitor respiratory status and cardiac rhythm during and after administration. Don’t be alarmed if the patient becomes RED, like worse than Doug from the Hangover red, after administration. Patient may be flushed/red due to the CN poisoning alone, but the Cyanokit will likely make it appear worse. Patient’s urine will likely be red post infusion as well. Both side effects generally resolve in 7-10 days.

For pregnant patients, it is classified as a Category C infusion and should be used if the potential benefit outweighs the risk in pregnant patients.


Overall, the process of setting up and administering the Cyanokit is pretty simple if you take the time beforehand to open up the kit and familiarize yourself with the contents. Knowing the indications puts you one step closer to delivering a life-saving intervention. Time matters when administering the kit and you owe it to that patient to be ready. This can be said about many of the products we use at our jobs. Don’t become complacent and be ready to do your job! Oh, and learn from my mistake, I sure did.


Strive to better yourself every day, even if it is 1% better than yesterday. This will make you become the person you want to be and others will follow your lead.



Tony Henry


References


-Cyanide poisoning diagnosis and treatment. (2019, January 22). Retrieved April 06, 2021, from https://youtu.be/FMMsSzGXJ9A


-CYANOKIT administration Video. (2017, February 27). Retrieved April 06, 2021, from https://youtu.be/bJEtw-4M-cE


-Nickson, C. (2020, November 03). Cyanide poisoning • litfl • ccc toxicology. Retrieved April 06, 2021, from https://litfl.com/cyanide-poisoning-ccc/


-Technologies, M. (n.d.). Time is of the essence. Retrieved April 15, 2021, from https://www.cyanokit.com/treatment-with-cyanokit#time-is-of-the-essence


-JEM-JOURNAL, E. (2011, April 29). Retrieved April 15, 2021, from https://www.jem-journal.com/article/S0736-4679%2811%2900287-3/abstract


-U. (2009, November 12). UMEM educational pearls. Retrieved April 15, 2021, from https://umem.org/educational_pearls/922/Uhl W, Nolting A,

Golor G, Rost KL, Kovar A. Safety of hydroxocobalamin in healthy volunteers in a randomized, placebo-controlled study.


-Clin Toxicol 2006;44:S17-S28.

Winter, B., & Simões, E. (2013, February 02). U.S. rushing treatment for Brazil fire victims. Retrieved April 15, 2021, from https://www.reuters.com/article/us-brazil-nightclub-deaths-idUSBRE9100ZF20130202


-ABC13, H. (2009, August 13). Houston fire department was the first nationally to utilize a cyanide Antidote kit for carbon


-Monoxide POISONING: ABC13 Houston. Retrieved April 15, 2021, from https://abc13.com/archive/6964290/


*All non-original photos/illustrations were used with permission and/or cited. *



P.S. Special thanks to Brittany Michelle, Michael Kaduce, my wife Nicole, and Taylor Soltau for their constructive criticism through the peer review process. Brittany even said it was pretty good for a “FireMedic.” Participating in something like this is a new adventure for me and I appreciate FOAMfrat’s willingness to share what I came up with. I hope everyone enjoyed.



Tony Henry