Must-Know EM Pharmacotherapy Articles of 2014


canstockphoto23105821There is so much literature to sift through each year, it becomes nearly impossible to stay abreast of it. Here is a quick summary of the 6 must-know Emergency Medicine pharmacotherapy articles from 2014, in my humble opinion.



1. High-Dose Droperidol and Risk of QT Prolongation2. Dexmedetomidine As Adjunct Therapy for EtOH Withdrawal - RCT3. A Simpler Dosing Regimen for Digoxin-Specific Antibody Fragments4. Treatment for Calcium-Channel Blocker Overdose: A Systematic Review5. Bactrim + ACE-Inhibitor (or ARB) + Older Adult = Increased Sudden Death6. Is That IV Antibiotic Before ED Discharge Really Necessary?
46 patients treated with high-dose droperidol (10-40 mg) were studied prospectively with continuous holter recording.

What they did

Patients initially received 10 mg droperidol as part of a standardized sedation protocol (for aggression). An additional 10 mg dose was given after 15 min if required and further doses at the clinical toxicologist’s discretion.

Continuous 12-lead holter recordings were obtained for 2-24 hours. QTc > 500 msec was defined as abnormal (with heart rate correction – QTcF).

What they found

Only 4 patients had abnormal QT measurements, three given 10 mg and one 20 mg. All 4 had other reasons for QT prolongation. No patient given > 30 mg had a prolonged QT. There were no dysrhythmias.

What it means

There was little evidence supporting droperidol being the cause and QT prolongation was more likely due to pre-existing conditions or other drugs.

Calver L, et al. High dose droperidol and QT prolongation: analysis of continuous 12-lead recordings. Br J Clin Pharmacol 2014;77(5):880-6. [PMID 24168079]

Originally posted Jan 4, 2014 as University of Maryland (UMEM, @UMEmergencyMed) pearl.

Four small case series (one prospective, 3 retrospective) have concluded that dexmedetomidine (Precedex) may be a useful adjunct therapy to benzodiazepines for ethanol withdrawal in the ED or ICU. They are summarized in a previous ALiEM post.

A new randomized, double-blind trial evaluated 24 ICU patients with severe ethanol withdrawal.

Group 1: Lorazepam + placebo

Group 2: Lorazepam + dexmedetomidine (doses of 0.4 mcg/kg/hr and 1.2 mcg/kg/hr).

  • 24-hour lorazepam requirements were reduced from 56 mg to 8 mg in the dexmedetomidine group (p=0.037).
  • 7-day cumulative lorazepam requirements were similar.
  • Clinical Institute Withdrawal Assessment or Riker sedation-agitation scale scores were similar within 24 hours.
  • Bradycardia occurred more frequently in the dexmedetomidine group.

In my opinion, a major limitation of this study is that patients had more than 24 hours of treatment before randomization. Eleven of the 24 patients were already intubated when the trial started. The best place to use dexmedetomidine is probably in the early treatment course to help avoid intubation altogether. I’m not sure this very exclusive trial (24 patients included/209 excluded over 4 years) provides any answers for the patients who may benefit most from this therapy. A reduction in benzodiazepines is not even the correct outcome to measure. That may lead to the erroneous notion that we don’t need benzodiazepines (as has happened in some of the other studies). We should be looking at reduction in intubations and ICU length of stay.

Mueller SW, et al. A randomized, double-blind, placebo-controlled, dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal. Crit Care Med 2014;42(5):1131-9. [PMID 24351375]

Originally posted May 3, 2014 as UMEM pearl.

Digoxin-specific antibody fragments (Fab) are safe and indicated in all patients with life-threatening dysrhythmias and an elevated digoxin concentration. However, full neutralizing doses of digoxin-Fab are expensive and may not be required (not to mention cumbersome to calculate).

Based on pharmacokinetic modeling and published data, a new review suggests a simpler, more stream-lined dosing scheme as follows:

  • In imminent cardiac arrest, it may be justified to give a full neutralizing dose of digoxin-Fab.
  • In acute poisoning, a bolus of 80 mg (2 vials), repeat if necessary, titrated against clinical effect, is likely to achieve equivalent benefits with much lower total doses.
  • With chronic poisoning, it may be simplest to give 40 mg (1 vial) at a time and repeat after 60 min if there is no response.

Chan BS, et al. Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Clin Toxicol 2014;52:824-36. [PMID 25089630]

In a precursor to a forthcoming international guideline on the management of calcium channel blocker poisoning, a new systematic review has been published assessing the available evidence.

A few findings from the systematic review:

  • The majority of literature on calcium channel blocker overdose management is heterogenous, biased, and low-quality evidence.
  • Interventions with the strongest evidence are high-dose insulin and extracorporeal life support.
  • Interventions with less evidence, but still possibly beneficial, include calcium, dopamine, norepinephrine, 4-aminopyridine (where available), and lipid emulsion therapy.

Stay tuned for the international guideline coming out soon. One treatment recommendation from the new guideline, reported at the 8th European Congress on Emergency Medicine September 2014, is not to use glucagon.

St-Onge M, et al. Treatment for calcium channel blocker poisoning: a systematic review. Clin Toxicol 2014;52:926-44. [free full-text PDF]

Originally posted October 9, 2014 as UMEM pearl.

A new population-based case-control study in older adults has linked the administration of trimethoprim-sulfamethoxazole (Bactrim, TMP-SMX) to increased risk of sudden death in patients also receiving angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB).

Hyperkalemia is the suspected cause. Compared to amoxicillin, TMP-SMX was associated with an increased risk of sudden death (adjusted odds ratio 1.38, 95% confidence interval 1.09 to 1.76) within 7 days of exposure to the antibiotic.

Practice Change

In older patients receiving ACE-Is or ARBs, TMP-SMX is associated with an increased risk of sudden death. When appropriate, alternative antibiotics should be considered.

Fralick M, et al. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population-based study. BMJ 2014;349:g6196. [Free open access link]

Many of the oral antibiotics prescribed in the ED have good bioavailability. So, a one-time IV dose before discharge generally won’t provide much benefit.

In fact, a new prospective study found that a one-time IV antibiotic dose before ED discharge was associated with higher rates of antibiotic-associated diarrhea and Clostridium difficile infection. One-time doses of vancomycin for SSTI before ED discharge are also not recommended (see Academic Life in EM post by Zlatan Coralic).

Bottom Line

Though there are a few exceptions, if a patient has a working gut, an IV dose of antibiotics before ED discharge is generally not recommended and may cause increased adverse effects. An oral dose is just fine.

Haran JP, et al. Factors influencing the development of antibiotic associated diarrhea in ED discharged patients home: risk of administering IV antibiotics. Am J Emerg Med 2014;32(10):1195-9. [PMID 25149599]

Originally posted December 6, 2014 as UMEM pearl.

Image credit: (c) Can Stock Photo

Bryan D. Hayes, PharmD, FAACT, FASHP

Bryan D. Hayes, PharmD, FAACT, FASHP

Chief Science Officer, ALiEM
Creator and Lead Editor, Capsules series, ALiEMU
Attending Pharmacist, EM and Toxicology, MGH
Assistant Professor of EM, Harvard Medical School
  • Mark Culver

    Great humble opinions. Saved our hospital $6,000 (and who knows how much for the patient) on DigiFab a few days ago with #3. Sure would be nice if we could get #1 back from national back order, I think it has been over 2 years now.

  • Kyle S.

    Following up on Article 6, do you have good reference table that provides comparison of bioavailability of IV vs oral formulations of antibiotics? I would live to have complete confidence in the oral-route-suffices rationale for outpatient (and ability to effectively summarize my with ED patients). Thanks

  • Jason West

    Bryan, this list is great!

    Article 1). Great that we can add evidence against Droperidol’s “black box” warning and help bring it back to the Pyxis med station (all 3 hospitals I’ve worked at don’t carry it).

    Article 6). I loved the article on not throwing a dose of Vanc at someone before they’re discharged to home. But one of our common practices in my ED residency is to give a gram of Ceftriaxone prior to discharging a patient with pyelo home with Cipro. Both drugs are bacteriocidal. In your opinion, is one dose of Ceftriaxone useful if you’re gonna discharge home with a fluoroquinolone? What the patient is sent home with Cefpodoxime or Keflex?

    • Bryan D. Hayes

      Jason, thanks for the kind words and the question.

      Treatment of pyelo can be tricky, and I think the guidelines only complicate the matter. They recommend a dose of a long-acting IV antibiotic (eg, ceftriaxone) if the FQ resistance rate is > 10% at your institution. Then the patient can go home with an oral FQ. To me, this makes little sense as I always try and give an equivalent version PO as was given IV. This received a class B-III recommendation and there were no references provided to support it. To me, if you’re not confident in your FQ (or Bactrim), don’t give it at all. There is some thought that even a one-time dose of ceftriaxone may be enough for some patients, but this has never been proven in the literature. We have an article in press right now that shows in otherwise healthy females with uncomplicated cystitis or pyelonephritis, the resistance to FQ is significantly lower than our ED antibiogram. In fact the resistance for cipro/levo to E. Coli was 2%. So, we’re more ok giving a dose of FQ in the ED and then sending them home on the oral version. If we choose ceftriaxone, we generally send the patient home on a cephalosporin such as cefpodoxime, cefuroxime, or even cephalexin on occasion.

      • Kyle S.

        If you’ve made the decision, prior to ED administration of antibiotic, that the pyelo patient WILL be discharged, is it necessary to give an initial dose of IV ABx? Why not oral from get-go?

        • Bryan D. Hayes

          An IV does is not always necessary. The guidelines say that for women with pyelonephritis requiring hospitalization, IV antibiotics should be used. They also say that a one-time IV dose of a long-acting antibiotic should be used (as above) in cases where FQs will be used but the local resistance exceeds 10%.

      • CJ

        Whoa, did you just say your paper shows that I can ignore the 40% resistance rate of fq, as reported by my institutions antibiogram and keep using fq for pyelo?? Life would be much easier!

        • Bryan D. Hayes

          At least in our ED, uncomplicated UTI/pyelonephritis in otherwise healthy females had 2% resistance to FQ for E. Coli vs 42% resistance in our ED antibiogram. It’s possible FQ may still be a viable option for some cases of pyelo. Paper is under review, so full results not available yet.

  • Steve G

    Have also a look at this article: Isbister GK, Calver LA, Page CB, Stokes B, Bryant JL, Downes MA. Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Ann. Emerg. Med. 2010; 56: 392-401.e1.
    Also should be using a QT nomogram rather than simply checking the QTc. See from the same author: Chan A, Isbister GK, Kirkpatrick CM, Dufful SB. Drug-induced QT prolongation and torsades de pointes: evaluation of a QT nomogram. QJM. 2007; 100: 609-15.
    We use droperidol in our department (Australia) for chemical restraint and will always check the QT on a nomogram if concerned about any overdose prolonging the QT. I highly recommend these if you haven’t read them or covered them previously.

  • TheSGem

    Hey Bryan, we covered your suggested must know EM Pharm article on antibiotic associated diarrhea on the Skeptics’ Guide to Emergency Medicine. #FOAMed #diarrhea