HYMR1

Wednesday, January 27, 2016

Trick of the Trade: Diphenhydramine for Local Anesthesia

Say you have any one of the following three scenarios in a patient who requires local anesthesia for repairing a minor wound laceration in the emergency department:

1 – Documented allergy to “-caine” agents (now, before you grumble…the patient assures you that this is a true allergy; yes, the whole nine yards with full-blown anaphylaxis that occurred years ago with some “-caine”).

2 – Shortage of all forms of parenteral lidocaine 1% and 2% (not a surprise, given the current climate of drug shortages that we routinely encounter in the emergency department).

3 – Close to nearing the toxic dose of your local anesthetic agent of choice…and in the rare circumstance, you have not yet achieved local anesthesia.

What is one to do to? You consult with one of your colleagues, who mentions that there has been some literature published related to the use of parenteral diphenhydramine as a local anesthetic.

Wait a minute…we’re talking Benadryl®? The same stuff that we prescribe to our patients here in the emergency department for all sorts of maladies on a daily basis?

Mind = blown.

Diphenhydramine (DPH) has been utilized as a local anesthetic for several decades. The earliest documentation of the evaluation of antihistamines in this capacity dates back to the 1940s, and with DPH specifically, its use as a local anesthetic in minor skin surgery was first described in 1956 (1). Other clinical applications of the use of DPH as a local anesthetic includes minor dental procedures and podiatric surgery. In terms of its mechanism of action in exertion of this effect, DPH and other H1 receptor antagonists will selectively bind to inactivated sodium channels, leading to stabilization of nerve cell membranes and inhibition of downstream depolarization. This has been hypothesized to be dependent upon the physical structure of DPH; for those readers interested in medicinal chemistry, the interaction of the compound with the inactivated sodium channel leading to the local anesthetic effect exhibited by DPH is attributed to the spatial configuration of the two phenyl moieties in close conjunction with the tertiary amine (2).

In terms of evidence of the use of DPH as a local anesthetic specific to emergency medicine, a number of case reports and clinical studies have been published evaluating its utility relative to other local anesthetics, including lidocaine and benzyl alcohol. In one validation study for its use as a dermal anesthetic, a prospective, randomized, double-blind, placebo-controlled study was conducted to assess both the degree of anesthesia (in square millimeters) and pain associated with injection in 24 subjects who received 0.5-mL injections of 1% DPH, 2% DPH, 1% lidocaine, and 0.9% sodium chloride placebo (3). Subjects who received 1% DPH achieved equivalent level of anesthesia relative to 1% lidocaine (p = 0.889); in addition, 1% DPH more effective in this outcome compared to 2% DPH. However, subjects did experience greater perception of pain at injection with both concentrations of DPH relative to 1% lidocaine (more pain perceived with 2% DPH), with some subjects experiencing persistent discomfort in the injected area for up to three days following injection. In another study evaluating other concentrations of DPH for local anesthesia, although a concentration of 0.5% DPH was deemed similar in perception of pain by patients upon injection compared to 1% lidocaine and a viable alternative to 1% lidocaine in maintaining local anesthesia, it was less effective than lidocaine when used for repairing minor skin lacerations in the face (4). In other head-to-head comparisons of 1% DPH and 1% lidocaine, similar levels and depths of local anesthesia were achieved (5-6).

With all of this mention of pain upon injection, it may be worth noting that the following statement can be found in the package insert for parenteral diphenhydramine (7):

“Use as a Local Anesthetic: Because of the risk of local necrosis, this drug should not be used as a local anesthetic.” 

However, most of the data related to this cautionary warning arose as a result of its properties as an irritant to the skin, and reactions observed such as local tissue ischemia and hyperemia have been associated with parenteral administration of high concentrations of DPH. In one of the earliest studies evaluating the use of lower concentrations of antihistamines to determine properties associated with local anesthesia, 1% DPH was generally well tolerated and this was the very basis for utilizing the lower specific concentrations in several of the studies discussed above (8). In fact, in one study, the tolerance associated with injection of 1% DPH was demonstrated to be even more so compared to 2% procaine (1).

The following recipe can be utilized to create a 1% DPH (10 mg/mL) solution using commercially available vials of 50 mg/mL (5%) parenteral DPH (9):

Ingredients:

One vial containing 50 mg/mL diphenhydramine for parenteral injection
0.9% sodium chloride
Needle and 10-mL syringe
Medication label

Steps:
  1. Draw up entire contents of vial containing 50 mg/mL diphenhydramine into the syringe. This should measure to a volume of 1 mL. 
  2. Dilute the contents of the syringe with 4 mL of 0.9% sodium chloride to yield a final volume of 5 mL. 
  3. Clearly label the contents of the syringe with the medication label as “Diphenhydramine 1% (10 mg/mL).”
Depending on the location and depth of the wound, the amount of 1% DPH necessary to induce local anesthesia may vary, and can range from 1 mL to 10 mL (9). One adverse effect to monitor for with administration and dose escalation of 1% DPH is the potential for sedation, which has been noted to occur in some patients (3).

Going back to our case above, you follow the recipe and prepare a 1% DPH solution for your wound lac, and you administer via injection a total of 2 mL of 1% DPH to your patient for the procedure. Your patient appears to be comfortable and you are able to seamlessly (pun intended) repair the wound lac without any untoward issues.

Done and done.

References:
  1. Steffen CG, Zimmerman M, Mihan R. Diphenhydramine hydrochloride as a local anesthetic agent. AMA Arch Derm 1956; 74:76-9. 
  2. Kuo CC, Huang RC, Lou BS. Inhibition of Na(+) current by diphenhydramine and other diphenyl compounds: molecular determinants of selective binding to the inactivated channels. Mol Pharmacol 2000; 57:135-43. 
  3. Green SM, Rothrock SG, Gorchynski J: Validation of diphenhydramine as a dermal local anesthetic. Ann Emerg Med 1994; 23:1284-1289. 
  4. Ernst AA, Marvez-Valls E, Mall G, et al. 1% Lidocaine versus 0.5% diphenhydramine for local anesthesia in minor laceration repair. Ann Emerg Med 1994; 23:1328-1332. 
  5. Dire DJ, Hogan DE. Double-blinded comparison of diphenhydramine versus lidocaine as a local anesthetic. Ann Emerg Med 1993; 22:1419-22. 
  6. Ernst AA, Anand P, Nick T, et al. Lidocaine versus diphenhydramine for anesthesia in the repair of minor lacerations. J Trauma 1993; 34:354-7. 
  7. Diphenhydramine hydrochloride injection. [package insert]. Franklin Lakes, NJ: BD Simplist; 2012. 
  8. Steffen CG, Mihan R, Zimmerman M. The evaluation of various antihistamines as local anesthetic agents. J Invest Dermatol 1957; 29:7-8. 
  9. Pollack CV, Swindle GM. Use of diphenhydramine for local anesthesia in "caine"-sensitive patients. J Emerg Med 1989; 7:611-4.

Friday, January 15, 2016

No More Epinephrine Ratios!

So long ratios!

We've covered epinephrine use and misadventures on this blog numerous times. (Megan's post here, Nadia's heremine here). One thing that they all have in common is brining up the risk of dosing errors as a result of it unique ratio expression format for its concentration. But those days are numbered.


Starting in May 2016, the ratio expression format for drug concentrations will no longer be permitted according to the December 2015 ISMP Acute Care report.1 This new development will apply to epinephrine, isoproterenol and neostigmine. Unaffected by this are the lidocaine and epinephrine combination solutions for local anesthesia.


The new labeling concentration notation will be a welcome change to pharmacist and patients alike. Confusion relating to the ratio concentrations of epinephrine (1:10,000 vs 1:1000) has been associated with numerous medication errors over the years, some leading to serious patient harm.2-8 In fact, in a controlled, non-patient care setting (classroom), physicians were more likely to cause an error in administration when epinephrine was labeled with ratio strengths compared to mass concentrations (OR 13.4, 95% CI 2.2 to 81.7).9


The new labeling for epinephrine will only be displayed as the mass concentration format used in virtually every other medication. For example, epinephrine 1:1000 will now be labeled as 1 mg/mL, and for the 1:10,000 as 0.1 mg/mL. Certainly this change will not prevent all medication errors. But as seen above, decimal points are involved, and however it may help reduce the incidence tremendously.



1. Intistute for Safe Medication Practices. Acute Care Medication Safety Alert Newsletter, December 2015. Available at https://www.ismp.org/Newsletters/acutecare/issue.aspx?id=1111, Accessed 1/15/2016
2. Dybvik T, Halvorsen P, Steen PA. Accidental intravenous administration of 50 mg of racemic adrenaline in a 2-year-old boy. Eur J Anesthesiol 1995; 12:181-183.
3. Karch S. Coronary artery spasm induced by intravenous epinephrine overdose. Am J Emerg Med 1989; 7:485-488.
4. Novey HS, Meleyco LN. Alarming reaction after intravenous administration of 30 mL epinephrine. JAMA 1969; 207:243-246.
5. Horek A, Raine R, Opie LH, et al. Severe myocardial ischemia induced by intravenous adrenaline. BMJ 1983; 268:519.
6. Hall AH, Kulig KW, Rumack BH. Intravenous epinephrine abuse. Am J Emerg Med 1987; 5:64-65.
7. Ferry DR, Henry RL, Kern MJ. Epinephrine-induced myocardial infarction in a patient with angiographically normal coronary arterias. Am Heart J 1986; 111:193-195.
8. Kanwar M, Irvin CB, Frank JJ, et al. Confusion about epinephrine dosing leading to iatrogenic overdose: a life-threatening problem with a potential solution. Ann Emerg Med 2010; 55:341-344.
9. Wheeler DW, Carter JJ, Murray LJ, et al. The effect of drug concentration expression on epinephrine dosing errors: a randomized trial. Ann Intern Med 2008; 148:11-14
.

Saturday, January 2, 2016

Goog Guy Rocuronium

As if you needed another reason to like rocuronium. I'm certain many of you are aware of this neat trick but I just discovered it while restocking the RSI kit.


Good guy rocuronium wants you to reduce medication errors by labeling your syringes!


Take a look: on this particular manufacturer's vial the label has an arrow in the top right corner of the orange area. Until literally 5 minutes ago, I thought it was nothing. But it actually peals off to be used as a label for a syringe!





Other medications have similar labels (like fentanyl), but few paralytics have these labels affixed to the vial itself. Certainly in the natural environment of the ED in a RSI setting, having appropriate labeling isn't always a priority (as much as it should be). However, this can serve as a handy identifier to remove confusion and prevent errors.

Happy new year!

Keep
calm
and
med safety



Featured Post

Giapreza - A Closer Look at the Pharmacology of Ang2

Angiotensin-II (Ang2) is now an FDA approved vasopressor. With this new addition to the available options, experts are combing over the ...