ACMT Toxicology Visual Pearl – Along Comes a Spider

Spider

What is this pictured spider that can inflict a deadly bite?

  1. Black Widow Spider (Latrodectus mactans)
  2. Brown Recluse Spider (Loxosceles reclusa)
  3. Redback Spider (Latrodectus hasselti)
  4. Sydney Funnel Web Spider (Atrax robustus)

[Image from thebeachcomber, CC BY 4.0 https://creativecommons.org/licenses/by/4.0, via Wikimedia]

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Trick of the Trade: Ultrarapid adenosine push for SVT with a pressure bag

With some things in life, speed is everything. Adenosine is one of those things. With an ultrafast half-life estimated to be between 0.6 to 10 seconds [1], parenterally administered adenosine needs to reach the cells of the AV-node and cardiac pacemaker cells in an expedited fashion to facilitate the termination of supraventricular tachycardias (SVTs).

Known Techniques of Adenosine Administration

Currently, there are 2-syringe and 1-syringe methods that are widely accepted for the administration of adenosine. Recent data suggests that they are non-inferior to each other [2].

Adenosine flush 2 syringe method

Classic 2-syringe method: Benefit = undiluted adenosine to the heart; Limitation = limited by the syringe flush volume [3]

adenosine single syringe method

1-syringe method: Benefit = large volume; Limitation = dilution of adenosine with IV fluid. Read more about the single syringe trick of the trade.

Trick of the Trade: Pressure bag setup

We propose administering undiluted adenosine in an ultra-rapid fashion via an in-line, primed saline tubing with a pressure bag setup.

adenosine iv tubing in y-injection site port

The unique aspect of the trick is to incorporate a high-pressure, unidirectional IV fluid administration system. It is similar to the 2-syringe system except that the flush syringe is replaced with high-pressure IV fluids.

How to set-up

  1. Setup a pressure bag with a primed saline line in the standard fashion.
  2. Close the roller clamp so that no IV fluid is flowing through the tubing.
  3. Attach the IV line to the patient’s angiocatheter.
  4. Attach a syringe with undiluted adenosine to the Y-site port as close to the patient’s IV as possible.
  5. Open the roller clamp to start the high-pressure IV fluid administration.
  6. Rapidly push the adenosine into the tubing.

Video demonstration

In this video, adenosine is the colored fluid for demonstration purposes. Notice how quickly the adenosine reaches the patient.

References

  1. Parker RB, McCollam PL. Adenosine in the episodic treatment of paroxysmal supraventricular tachycardia. Clin Pharm. 1990 Apr;9(4):261-71. PMID: 2184971.
  2. Miyawaki IA, Gomes C, Caporal S Moreira V, et al. The Single-Syringe Versus the Double-Syringe Techniques of Adenosine Administration for Supraventricular Tachycardia: A Systematic Review and Meta-Analysis. Am J Cardiovasc Drugs. 2023;23(4):341-353. doi:10.1007/s40256-023-00581-w. PMID 37162718
  3. Kotruchin P, Chaiyakhan I, Kamonsri P, et al. Abstract 10470: Comparison between the double-syringe technique and the single-syringe diluted with normal saline technique of adenosine for a termination of supraventricular tachycardia: A pilot, randomized, single-blind controlled trial (DO-single trial). Circulation. 2021;144(Suppl_1). doi:10.1161/circ.144.suppl_1.10470

Cocaine for Epistaxis: What was old is new again

cocaine for epistaxis

Droperidol is back! Routine use of calcium for cardiac arrest is out? TPA is… well, we won’t go there. The landscape of medicine is continuously being reshaped. New research may question the effectiveness of an existing medication or promote the arrival of a novel treatment. Once beloved medications sit dust-laden in the back of a hospital pharmacy. But sometimes, just sometimes, an old medicine arises from that dust. Phenobarbital for alcohol withdrawal comes to mind.

Could cocaine hydrochloride be one of those medications to be resurrected?

Cocaine is effective in the treatment of epistaxis. Epistaxis is an exceedingly common complaint, accounting for approximately one in 200 emergency department (ED) visits in the United States [1, 2]. If you ask any seasoned emergency physician their ideal approach to epistaxis management, chances are high that it used to include cocaine. They will exclaim how superior it was to anything used today and claim, “Not only did it vasoconstrict, but it anesthetized, as well!” If this is the case, why is cocaine hydrochloride no longer used?

This post will chronicle cocaine’s fascinating yet troubled history in medicine and expose you to another tool for your arsenal in the ED management of epistaxis.

History

The coca plant, native to South America, Mexico, Indonesia, and the West Indies, derives its name from the Aymaran word Khoka meaning “the tree” [3]. Coca leaves contain approximately 0.25 to 0.9% cocaine. Their use medicinally dates as far back as 1000 BC by the indigenous people of South America. The leaves were chewed for energy supplementation and altitude sickness relief. During the Incan Empire of the 13th to 16th century, the leaves were revered as sacred and served as a panacea or cure-all. Coca was used to aid in digestion, pain relief, mitigation of hunger, wound healing, and even as a local anesthetic for invasive procedures, such as cranial trephination [3, 4].

It was not until the mid-1800s that cocaine’s journey began in Europe with the German chemist, Albert Nieman. Neiman isolated the alkaloid cocaine from the coca leaf and noted its numbing properties when placed on the tongue [5]. Its anesthetic and vasoconstricting properties were soon recognized by Austrian Professor C.D. Schroff and Peruvian physician, Dr. Thomas Mareno y Maiz [4]. Its popularity in medicine, however, had yet to catch on [4–6].

1884 marked a pivotal year for cocaine use in medicine. Austrian ophthalmologist, Dr. Carl Koller, introduced cocaine as a local anesthetic for cataract and other eye surgeries, which was a groundbreaking advancement. He additionally suggested its use for additional procedures of the nose, pharynx, and larynx [4, 5, 7]. Simultaneously, Sigmund Freud, the famed Austrian neurologist, became fascinated with cocaine’s various applications and wrote Uber Coca, the first of his 5 papers on the subject. He touted it as a “magical substance” without addictive properties. Ironically – and unfortunately – Freud later realized his misjudgment and spent years grappling with cocaine addiction [4, 5, 7].

Cocaine’s use as a local and regional anesthetic spread widely across Europe and to America from there. Influential American surgeons like Dr. William Halstead, a founder of Johns Hopkins School of Medicine, and his student, Dr. James Corning, further advanced its clinical applications by using cocaine as the first agent for regional nerve blocks and spinal anesthesia [8]. Like Freud, Dr. Halsted became addicted to cocaine and later morphine, which he used to wean his cocaine addiction.

In the early 1900s the medical use of cocaine declined due to increased reports of side effects, the development of safer alternatives such as procaine, and strict regulatory measures such as the 1914 Harrison Narcotics Tax Act [9].

Today’s Use in Medicine

Most of today’s medical use of cocaine is by the Ear, Nose and Throat (ENT) community. In fact, the American Academy of Otolaryngology-Head and Neck Surgery has had a position statement on cocaine since 1886 that reads [10]:

The American Academy of Otolaryngology-Head and Neck Surgery considers cocaine to be a valuable anesthetic and vasoconstricting agent when used as part of the treatment of a patient by a physician. No other single drug combines the anesthetic and vasoconstricting properties of cocaine.

FDA Approval

Cocaine hydrochloride is FDA-approved for local anesthesia for adult nasal procedures. Though not FDA-approved, it is also commonly used by ENT physicians as a hemostatic agent to prevent post-procedure bleeding and as a decongestant to promote a clearer view of the nasal passageways during surgery [11–14]. In the ED, it has been used off-label to treat epistaxis [11, 13, 15, 16] and as an anesthetic and analgesic before fiberoptic nasotracheal intubation [8].

Mechanism of Action

Cocaine is an alkaloid ester with weak basic properties. The addition of hydrochloride salt forms cocaine hydrochloride. In this form, cocaine is soluble in aqueous solution and can be used for ENT procedures. Its anesthetic properties occur via blockage of voltage-gated sodium channels. Vasoconstriction and hemostasis occur due to inhibition of catecholamine reuptake, including norepinephrine [9, 11].

Pharmacokinetics

  • Intranasal absorption: 4-33% [17–19]
  • Onset: 2-5 minutes [8]
  • Duration: 30-45 minutes [8]

Preparations

Cocaine hydrochloride is a clear, green solution. It comes in a single-unit bottle with concentrations ranging from 4-10%. Only the 4% solution is currently recommended as it has similar efficacy to higher concentrations with fewer side effects [11, 22]. The 10% solution should be avoided as it has been associated with toxicity and adverse events [8, 17, 20, 23]. Typically the 4% solution is dispensed in 1 mL or 4 mL single-use bottles.

Efficacy

There is limited research available on the use of intranasal cocaine in the ED for epistaxis management, or any other condition. Studies from the ENT literature have shown that cocaine has similar efficacy to most vasoconstrictors including epinephrine and phenylephrine for preventing bleeding after intranasal procedures [26–30]. The literature is mixed on oxymetazoline (Afrin) in epistaxis with some studies showing it may have superior efficacy in preventing post-procedure epistaxis [31, 32]. However, oxymetazoline lacks any anesthetic properties.

Safety

Concerns about cocaine hydrochloride’s intranasal use primarily revolve around its potential for systemic cardiovascular toxicity. Historical case reports of varying quality have documented significant adverse events including myocardial infarction (MI) and cardiac arrhythmias following intranasal use during ENT procedures and epistaxis management [21, 33, 34]. A dive into these reports, however, shows that a concentration and dose over the accepted 4% concentration and 200 mg maximum dose was frequently used in these cases. Many confounders also existed, such as a history of cardiac disease and concomitant medication administration (including general anesthesia) [34, 35]. There have been many contemporary studies comparing cocaine to other vasoconstricting/anesthetic agents in the ENT literature. In these studies, cocaine has not been shown to cause serious adverse CNS or cardiac events including MI, dangerous arrhythmias, or death [28, 32, 36–41].

It is important to note that most of the randomized control studies excluded patients with cardiac disease. It is therefore recommended to avoid the use of cocaine in patients with a history of MI, CAD, congenital heart disease, or uncontrolled hypertension [18, 34]. Cocaine should also be avoided in patients on beta-blocker therapy, from limited studies demonstrating increased coronary vasoconstriction with concomitant administration [20, 42].

Side Effects

The most common side effects are mild blood pressure elevation, mild tachycardia, non-emergent headache, and anxiety [18, 43]. Although rare, signs to watch for that could indicate severe CNS or cardiovascular toxicity include: agitation, seizure activity, hyperthermia, significant hypertension, significant tachycardia or arrhythmias, chest pain, and MI [25, 34].

It is recommended that patients receiving intranasal cocaine should have continuous cardiac monitoring and frequent vital sign checks, assessing for hypertension and tachycardia [21].

Contraindications [11, 24, 25]

Absolute

  • History of allergy to cocaine or substitutes of topical solution

Relative

  • History of cardiovascular disease (uncontrolled hypertension, unstable angina, MI, coronary artery disease, congestive heart disease, congenital heart disease): Increased risk of cardiac adverse event
  • Seizure/epilepsy history: May decrease seizure threshold
  • Active asthma exacerbation: May cause bronchoconstriction
  • Drug interactions:
    • Beta-blockers: May lead to hypertensive crisis through unopposed alpha-adrenergic vasoconstriction
    • Lidocaine/category 1A & 1C antiarrhythmics: Concurrent sodium channel blockade
    • Epinephrine or phenylephrine: Historical reports of MI and ventricular arrhythmia
    • Succinylcholine: Co-metabolism by plasma cholinesterase may lead to increased toxicity
    • Selective Serotonin Reuptake Inhibitors (SSRIs): Increased risk of seizures
    • Monoamine Oxidase Inhibitors (MAOIs): Prevent breakdown of catecholamines and can lead to toxicity
    • Disulfiram: Increases plasma cocaine and could lead to toxicity

Special Populations

  1. Pregnancy: Category C (may cause fetal harm). Avoid use during pregnancy [24, 25].
  2. Lactation: Avoid use during lactation [25].
  3. Pediatric: Not well studied

Barriers to Use

  1. Regulations
    • Schedule II drug (high potential for abuse with potentially severe psychological or physical dependence)
    • Requires storage in a locked cabinet and maintenance of separate written records of use
  2. Time to treatment: May take longer to obtain from the pharmacy compared to alternatives, given storage considerations and whether dispensed from the hospital (rather than ED) pharmacy
  3. Drug testing: Discuss with patients before use that cocaine may be detected up to 1 week in blood and even longer in urine [25].

Applying Cocaine in Epistaxis (24, 25)

  1. You will need at least 80 mg of 4% cocaine hydrochloride.
    • If your hospital stocks the 1 mL bottle of 40 mg/mL cocaine hydrochloride, you should obtain 2 vials (80 mg total). Use 2 separate pledgets, immersing each one in its own bottle.
    • Alternatively, if your hospital stocks the 160 mg/4 mL solution, soak 4 pledgets in the entire 4 mL solution.
    • Each pledget will absorb approximately 1 mL of the 4% solution.
  2. Once fully adsorbed, place 1-2 pledgets in the nasal cavity with epistaxis, positioned against the septum.
  3. Leave the pledgets in place for up to 20 minutes.
  4. Assess for hemostasis.
  5. If needed, you can use a maximum of 2 additional pledgets, if epistaxis does not resolve. The maximum dose should be the lower dose of 200 mg or 2 mg/kg.

Proposed ED Epistaxis Algorithm [16, 44]

Takeaways

  1. In the right patient, cocaine may have a place in the management of epistaxis. Avoid in patients with cardiovascular disease.
  2. Cocaine is the only single agent that both vasoconstricts and anesthetizes.
  3. Insert 1-2 pledgets soaked each with 40 mg of cocaine hydrochloride into the affected nare for 20 minutes.
  4. The maximum dose is 2 mg/kg or 200 mg, whichever is lower.

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  2. Pallin DJ, Chng YM, McKay MP, Emond JA, Pelletier AJ, Camargo CA. Epidemiology of epistaxis in US emergency departments, 1992 to 2001. Ann Emerg Med. 2005;46(1):77-81. doi:10.1016/j.annemergmed.2004.12.014. PMID: 15988431
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  20. Lange RA, Cigarroa RG, Yancy CW, et al. Cocaine-induced coronary-artery vasoconstriction. N Engl J Med. 1989;321(23):1557-1562. doi:10.1056/NEJM198912073212301. PMID: 2573838
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  40. Alhaddad ST, Khanna AK, Mascha EJ, Abdelmalak BB. Phenylephrine as an alternative to cocaine for nasal vasoconstriction before nasal surgery: A randomised trial. Indian J Anaesth. 2013;57(2):163-169. doi:10.4103/0019-5049.111844. PMID: 23825816
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  42. Lange RA, Cigarroa RG, Flores ED, et al. Potentiation of cocaine-induced coronary vasoconstriction by beta-adrenergic blockade. Ann Intern Med. 1990;112(12):897-903. doi:10.7326/0003-4819-112-12-897. PMID: 1971166
  43. Drivas EI, Hajiioannou JK, Lachanas VA, Bizaki AJ, Kyrmizakis DE, Bizakis JG. Cocaine versus tetracaine in septoplasty: a prospective, randomized, controlled trial. J Laryngol Otol. 2007;121(2):130-133. doi:10.1017/S0022215106002386. PMID: 17274862.
  44. Gottlieb M, Long B. Managing Epistaxis. Ann Emerg Med. 2023;81(2):234-240. doi:10.1016/j.annemergmed.2022.07.002. PMID: 36117013

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