Cyanide Toxicity Distilled

Public service announcement: Don’t drink the Koolaid® (google Jonestown mass suicide)  Cyanide Toxicity

After a lecture today with our fantastic Maimo paramedics today, Dr. Lobel had insightful and nuanced feedback regarding treatment of cyanide toxicity and the current REMAC protocol.

Exposure: 

Typically, it is due to combustion of nitrogen containing polymers (think couches and kevlar)

Metallurgists, jewelers, and those working with electrolysis may have vats of liquid cyanide laying around; so, be wary. 

IV nitroprusside can also cause cyanide toxicity, even when administered in therapeutic doses. 

Also, apparently the hydrolysis of Amygdalin, which is present in cassava beans, peach pits, and apples seeds produces cyanide. So, depending on the quantity ingested, toxicity may become apparent. For the purposes of this POD, we will not go into the details of chronic CN toxicity. 

Mechanism: 

Cyanide inhibits: superoxide dismutase, carbonic anydrase, CYTOCHROME OXIDASE, succinic acid dehydrogenase.

Obviously, this causes inhibition of cellular metabolism, specifically the-critical-to-cellullar-survival Mitochondrion. 

Syptoms: 

Unfortunately they are non-specific, and overlap with CO toxicity. 

They can include:

Headache, anxiety, ams, lethargy

Cardiovascular collapse

Progressing to the seizure, coma, death pathway

Any unexplained lactic acidosis > 8 mmol/dL, CN toxicity should be considered. 

Treatment: 

As per Goldfrank’s Emergency Toxicology, 74% of confirmed cyanide cases did not receive an appropriate antidote. 

Past treatments included amyl nitrites (aka the “popper”), but this induces methemoglobinemia; therefore this should be avoided at all costs in a patient whose presumed exposure to cyanide gas could also be a concomitant carbon monoxide exposure. 

Hydroxycobalamin is probably the best go to if you only have one antidote available because when administered IV, it directly binds CN with high avidity. Therefore, when CN concentration in the plasma decreases, the CN inside the cells equilibrates down the gradient and shifts CN out of the cells, restoring the mitochondrial electron transport chain. 

This is where LOBEL’S ADVICE was really helpful:

Sodium thiosulfate is a useful adjunct because it recycles Cyano-met-Hgb to met-Hgb. It does not create more met-Hgb like the amyl-nitrites do. So, sodium thiosulfate can be safely administered along with cyanokit to create an additive effect. 

Of note, there are numerous case reports of patients being pulled from fires in cardiac arrest who achieve ROSC only after cyanokit has been administered. 

With that being said, I have a attached a case report from 1970 he gave me. It is a fantastic read and quite hilarious regarding the description of the patient’s tragic tattoos, so definitely give it 2 minutes. 

Local IV contrast infiltration

Just imagine this scenario: you are concerned that your patient has a pulmonary embolus. They are tachycardic, hypoxic on room air, but BP’s are stable (for now). They were a tough stick and 2 nurses tried for 5 minutes, so under real time ultrasound guidance you place what you think is an expert 20g x 48mm angiocath in their right cephalic vein. You dial 6308 and ask the radiology technologist to scan the patient next, then you are off to see the next patient on a busy north side shift.

15 minutes later, you get a call: “Ummmm… Doc, patient x…. that line blew. They got the hole load in the right arm. Can you come take a look?”

This can happen about 0.24% of patients who receive IV contrast in the upper extremity (or about 1/400 studies).

UNDERSTANDING CONTRAST:

The Omnipaque™ we use for our IV contrast CT studies is Iohexol:

Here is its structure:

The concentration we use is 350 mg/mL, this results in a total osmolality of 844 mOsm/kg water. This is approximately 3 times the osmolality of serum. However, given the fact it is non-ionic, it does not cause a significant osmolar effect. Nonetheless, infiltration will lead to fluid shift of H2O down its gradient into the tissue compartment the infiltrated contrast material occupies, which is typically the interstitial space. This has been shown experimentally in a renal model: after contrast load urine output increases because the iohexol is renally excreted.

The most danger for infiltration occurs with high flow rates achieved during CT angiography studies. As per our technologist on our Siemens machine, the auto injector we use has a flow rate 4-5 mL/s achieved with a pressure gradient anywhere from 50-100 psi. If the IV has poor flow due high intracatheter or intravenous resistance, then the pressure can increase to upward of 400 PSI to achieve flow. When this high pressure occurs, the IV can become dislodged. Remember Newtonian mechanics: Pressure exerts a force, and for each force there is an equal and opposite reaction.

MANAGEMENT OF IV INFILTRATION OF A CONTRAST LOAD:

####first and foremost, you need to inform the patient what happened. Explain why this happened. Apologize for the complication. Address any pain issues. Tell them how you and the team will care for their likely painful upper extremity. Finally, you can reassure them for the reasons below.

*Gradually, the infiltrated contrast will diffuse out of the tissue compartment and back into the serum. This diffusion can be enhanced with gentle warm compresses.

**Plastic surgery recommendations for this complication are elevation of the extremity, local massage, and frequent neuromuscular checks.

***In a study of 102 cases of IV contrast extravasation in the upper extermity, surgical intervention was required in 0. The surgeons behind this study recommend surgical consultation if there obvious signs of skin compromise or compartment syndrome.

****compartment syndrome has been reported in the case literature, so please, please, please, watch for that. The incidence is on case report level, so it is likely very, very low.

SOME TIPS PREVENTION OF IV INFILTRATION OF US GUIDED PIV’s:

*Always use the 48 mm angiocath

**The more of the catheter that is in the lumen of the vein, the less likely it is to become dislodged. So a good rule of thumb is at least 1 cm of the catheter within the lumen of the vein. So any target >2cm deep to the skin will be difficult to properly position using a 45 degree angle of approach.

One fun final fact: non-ionic iodinate contrast materials are procoagulants and as per the FDA they should be avoided at all cost patients with homocystinuria.

References:

https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/018956s095,020608s031lbl.pdf

https://www.sigmaaldrich.com/catalog/substance/iohexol821146610895011?lang=en®ion=US

Jonas Pologe’s US PIV POD

Belzunegui T, Louis CJ, Torrededia L, Oteiza J. Extravasation of radiographic contrast material and compartment syndrome in the hand: a case report. Scand J Trauma Resusc Emerg Med. 2011;19:9.

Sbitany H, Koltz PF, Mays C, Girotto JA, Langstein HN. CT contrast extravasation in the upper extremity: strategies for management. Int J Surg. 2010;8(5):384-6.

Solomon R. Contrast media: are there differences in nephrotoxicity among contrast media?. Biomed Res Int. 2014;2014:934947.

Iohexol image curtesy wikipedia public domain, no limitations.

Local Anesthetic Toxicity

LOCAL ANESTHETIC TOXICITY, as available in our ED (4% cocaine and street cocaine will be addressed in a different post; tetracaine omitted). There are definitely more “caines”, but I want to address the “caines” that we use on a daily basis.

Toxic doses by drug (there are other “caines”, but these are most commonly used in our ED):

Lidocaine 1%: 4.5 mg/kg, max off-the-cuff dose is 300 mg. 1 vial is 50 mL and 500 mg, so try not to give a full vial, please.

Lidocaine 1% w/ epi: 7 mg/kg. Max dose is 500 mg or 50 mL.

Lidocaine 2% Viscous: special note that in children, as little as 5 mL can cause seizure

#paindosing Lidocaine IV dosing is 1.5 mg/kg, with a max of 200 mg, please note this is significantly below toxic dosing for local infiltration. The literature suggests 800 mg is the lower end of IV toxic dosing in adults.

Benzocaine 20% (aka hurricane spray), indicated doses are two 1 second sprays into the oropharynx (methemoglobinemia has been induced with these indicated doseages).

Bupivacaine 0.25%: 2 mg/kg, max total dose is 175 mg, or 70 mL.

Bupivacaine 0.25% w/ epi is 3 mg/kg, max total dose is 225 mg or 90 mL.

Mechanism of toxicity:

Na+ channel blockade, causing cardiac and central nervous system effects.

Methemoglobinemia is a risk for both ester and amide anesthetics, but it is more commonly associated with benzocaine and lidocaine.

Clinical effects of toxicity:

***first effects classically involve peri-oral paresthesias

Hypotension

Motor Paralysis

QRS prolongation

Tachydysrhythmia

Bradycardia -> asystole

Respiratory paralysis

Seizures

Prilocaine and Benzocaine are associated with methemoglobinemia (neither of which are used in our ED, but may be encountered OTC), so get a cooximetry.

Treatment of local anesthetic toxicity:

*Hypotension: give fluids, pressors, avoid calcium channel blockers, avoid beta blockers, avoid lidocaine.

**If systemic effects with cardiac involvement: give Intralipid 20%: This is available in room 22 (nerve block cart) and Resus 4; Dosing is 1.5 mL/kg as an IV bolus; Then make a drip of 0.25 mL/kg/min. (max 10 mL/kg/min)

***Treat seizures with Benzodiazepenes.

****If you cause methemoglobinemia, give methylene blue 1 mg/kg over 30 minutes with a repeat dose if MetHGb is >30% after 1 hour, or symptoms persist (eg, end organ damage), BUT PLEASE DRAW LABS PRIOR TO ADMINISTRATION because the dye may affect future laboratory tests that depend on photometric assay.

#intralipidspecialnote: if QRS acutely widens to greater than 120 ms, this is an indication of impending clinical decompensation and intralipid should be administered.

Final Side Note:

If a patient is allergic to any of the “caines” (cocaine included), you can always put together a 1% diphenhydramine solution, which has been shown to be non-inferior to lidocaine when infiltrated locally for anesthetic purposes. One caveat is that the time to onset of anesthesia is slightly longer.

Final, final aside: how to make 1% diphenhydramine solution

1 Get 50 mg vial of diphenhydramine, which comes in a 1 mL at our shop.

2 Get 4 mL NS in a sterile syringe, put 1 mL of 50 mg /mL and draw diphenhydramine solution into the syringe.

3 This will bring your total solution volume to 5 mL.

4 Thats 50 mg in 5 mL, or 10 mg/mL

5 Remember 1 mL weighs 1 gram, or 1000 mg.

6 Therefore 10 mg diphenhydramine to 1000 mg NS, which is a 1% solution.

7 Keep in mind some of this will eventually redistribute to the vascular compartment and eventually other tissues (eg CNS), so I would not dose more than 50 mg total for an adult-sized human.