UMEM Educational Pearls - Pharmacology & Therapeutics

Category: Pharmacology & Therapeutics

Title: Blood Glucose Response to Rescue Dextrose

Keywords: blood glucose, dextrose, hypoglycemia (PubMed Search)

Posted: 7/26/2015 by Bryan Hayes, PharmD (Emailed: 8/1/2015) (Updated: 8/1/2015)
Click here to contact Bryan Hayes, PharmD

How much does the blood glucose concentration increase when dextrose 50% (D50) is administered?

A new study found a median increase of 4 mg/dL (0.2 mmol/L) per gram of D50 administered.

This retrospective study was conducted in critically ill patients who experienced hypoglycemia while receiving an insulin infusion. While it may not directly apply to all Emergency Department patients, an estimation of the expected blood glucose increase from rescue dextrose is helpful. If the blood glucose doesn't respond as anticipated, it can help us troubleshoot possible issues (eg, line access).

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Category: Pharmacology & Therapeutics

Title: Early Glargine Administration at Start of DKA Treatment

Keywords: diabetic ketoacidosis, insulin, glargine, DKA (PubMed Search)

Posted: 6/29/2015 by Bryan Hayes, PharmD (Emailed: 7/4/2015) (Updated: 7/4/2015)
Click here to contact Bryan Hayes, PharmD

Transitioning Diabetic Ketoacidosis (DKA) patients off an insulin infusion can be challenging. If a long-acting insulin, such as glargine or levemir, is not administered at the correct time to provide extended coverage, patients can revert back into DKA.

Pilot Study

A prospective, randomized, controlled pilot study in 40 patients evaluated administration of glargine within 2 hours of insulin infusion initiation compared to waiting until the anion gap (AG) had closed.

What they did

  • All patients received IV insulin.
  • Experimental: Subcutaneous insulin glargine given within 2 hours of diagnosis.
  • Control: Patients subsequently transitioned to long-acting insulin upon closure of AG.

What they found

Mean time to closure of AG, mean hospital LOS, incidents of hypoglycemia, rates of ICU admission, and ICU LOS were all similar between the groups.

Application to Clinical Practice

Although just a pilot study (using a convenience sample), early glargine administration seemed to be absorbed adequately (based on time to AG closure) and was not associated with increased risk of hypoglycemia. If confirmed in a larger study, this technique could help optimize care of DKA patients in the ED by eliminating the often-mismanaged transition step later on.

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Category: Pharmacology & Therapeutics

Title: Vancomycin Loading in Obese Patients

Keywords: obese, vancomycin, loading dose (PubMed Search)

Posted: 5/22/2015 by Bryan Hayes, PharmD (Emailed: 6/6/2015) (Updated: 6/6/2015)
Click here to contact Bryan Hayes, PharmD

Vancomycin guidelines recommend an initial dose of 15-20 mg/kg based on actual body weight (25-30 mg/kg in critically ill patients). [1] The MRSA guidelines further recommend a max dose of 2 gm. [2]

But, what dose do you give for an obese patient that would require more than 2 gm?

A new study provides some answers to this question. [3] Obese-specific, divided-load dosing achieved trough concentrations of 10 to 20 g/mL for 89% of obese patients within 12 hours of initial dosing and 97% of obese patients within 24 hours of initial dosing.

Application to Clinical Practice

  1. Calculate the total loading dose. At my institution we use actual body weight (the study used IBW).
  2. Divide the total dose to be given every 6 hours until load is complete. We cap each individual dose at 2 gm (the study used 1.5 gm).
  3. Measure a trough level before the third dose.
  4. Change to dosing frequency dictated by renal function once level moves into target range.


The study used some more specific dosing calculations based on renal function and percentage above IBW. If patient's renal function is abnormal, consultation with a pharmacist is recommended.

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Category: Pharmacology & Therapeutics

Title: Sodium Content of Emergency Department Antibiotics

Keywords: sodium, piperacillin/tazobactam, ampicillin, moxifloxacin, metronidazole (PubMed Search)

Posted: 4/13/2015 by Bryan Hayes, PharmD (Emailed: 5/2/2015) (Updated: 5/2/2015)
Click here to contact Bryan Hayes, PharmD

Aside from sodium chloride and sodium bicarbonate, several commonly used emergency department medications (namely IV antibiotics) contain a significant amount of sodium. In patients with heart failure or other conditions requiring sodium restriction, judicious use should be considered.


  • Available references all quote slightly differing sodum contents. Therefore, the daily totals are approximate, but within 100 mg of the various references.
  • To convert mg to mEq or mmoL, divide by 23.

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Category: Pharmacology & Therapeutics

Title: Clindamycin vs. Trimethoprim-Sulfamethoxazole for Uncomplicated Skin Infections

Keywords: clindamycin, SSTI, skin infection, Bactrim, trimethoprim-sulfamethoxazole (PubMed Search)

Posted: 3/20/2015 by Bryan Hayes, PharmD (Emailed: 4/4/2015) (Updated: 4/4/2015)
Click here to contact Bryan Hayes, PharmD

For many institutions, clindamycin is not as good as it used to be for methicillin-resistant Staph aureus (MRSA). When treating skin and soft tissue infections (SSTI), this can be challenging. Clindamycin still covers skin strep species very well, but not always the staph. On the other hand, trimethoprim-sulfamethoxazole (TMP-SMX) covers staph really well, but not so much the strep.

What They Did

A new double-blind, multicenter, randomized study in NEJM compared these two antibiotics in 524 patients with uncomplicated skin infections who had cellulitis, abscess larger than 5 cm, or both. All abscesses underwent incision and drainage. The primary outcome was clinical cure rate 7-10 days after the end of treatment.

What They Found

There was no difference in clinical cure rate between the two groups (80.3% for clindamycin, 77.7% for TMP-SMX).

Problems with the Study

  • Uncomplicated abscess shouldn't require antibiotics.
  • The dose of TMP-SMX was one DS tab equivalent, yet weights weren't reported. That dose may not be sufficient for all patients.
  • Only 12% of the MRSA that grew was resistant to clindamycin, which is less than local patterns at many institutions. This limits generalizability.

Application to Clinical Practice

Unknown. This study seems to suggest TMP-SMX might be ok in uncomplicated cellulitis even though we assume strep species are the causitive organism. However, we already know cephalexin is equivalent to cephalexin + TMP-SMX from the 2013 study by Pallin et al. Why not just use cephalexin which has less adverse effects than TMP-SMX?

With such low clindamycin resistance, even to the staph species, perhaps that is why the two treatments were similar. Also, why did successfully drained abscesses need antibiotics? Finally, there were many exclusion criteria which eliminated many of the patients we see in the ED.

For a different, critical perspective of this NEJM study, Dr. Ryan Radecki gives his thoughts on his EM Lit of Note blog.

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Category: Pharmacology & Therapeutics

Title: Low-Dose Ketamine for Pain Management in the ED

Keywords: ketamine, pain, opioid (PubMed Search)

Posted: 2/24/2015 by Bryan Hayes, PharmD (Emailed: 3/7/2015) (Updated: 3/7/2015)
Click here to contact Bryan Hayes, PharmD

Emergency Departments are increasingly searching for alternatives to opioids for acute pain management.

An urban trauma center in California retrospectively evaluated their use of low-dose ketamine for acute pain over a two-year period. [1]

  • 530 patients
  • Indications were separated in 7 broad categories such as abdominal pain, back pain, and musculoskeletal pain
  • Ketamine dose: 10-15 mg (93% IV, 7% IM)
  • No significant changes in heart rate or blood pressure
  • 30 patients (6%) experienced adverse effects (psychomimetic/dysphoric reactions, transient hypoxia, emesis) - none were classified as severe based on authors' definitions

Application to Clinical Practice

There was no comparison group and there was no mention of what other pain medicines were given. Adverse events are often under-reported in retrospective studies. This study seems to demonstrate that low-dose ketamine administration for acute pain management in the ED is feasible with a low rate of adverse effects.

It's worth noting that a new review of 4 randomized controlled trials evaluating subdissociative-dose ketamine found no convincing evidence to support or refute its use in the ED. The 4 included trials had methodologic limitations. [2]

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Category: Pharmacology & Therapeutics

Title: Vancomycin Loading in the ED Leads to Higher Trough Levels

Keywords: vancomycin, loading dose (PubMed Search)

Posted: 1/26/2015 by Bryan Hayes, PharmD (Emailed: 2/7/2015) (Updated: 2/7/2015)
Click here to contact Bryan Hayes, PharmD

We know vancomycin should be dosed based on weight rather than the default 1 gm dose so many patients receive. A past Academic Life in EM post explores the nuances of proper vancomycin dosing. But do higher loading doses in the ED actually lead to more therapeutic trough levels?

New Data

A new randomized trial compared ED patients receiving 30 mg/kg initial doses vs. 15 mg/kg. [1] There was a significantly greater proportion of patients reaching target trough levels of 15 mg/L at 12 hours among the patients who received a 30 mg/kg loading dose as compared with a traditional 15 mg/kg dose (34% vs 3%, P < 0.01). This study did not use a max dose of 2 gm. They included patients up to 120 kg who received 3.6 gm loading doses! Patients with creatinine clearance < 50 mL/min were excluded. There was no difference in incidence of nephrotoxicity between the groups.

Application to Clinical Practice

  • Advocate for change in your ED's order sets to weight-based dosing of vancomycin and remove 1 gm as a default option. [2, 3]
  • While 34% attaininment of adequate trough levels still isn't great, properly loading vancomycin with up to 30 mg/kg is a step in the right direction. It also takes longer than one dose to reach steady-state levels.
  • This study did not evaluate clinical cure rates, just trough levels.

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Category: Pharmacology & Therapeutics

Title: IV Magnesium for Acute Migraine Headache

Keywords: headache, migraine, metoclopramide, magnesium (PubMed Search)

Posted: 12/31/2014 by Bryan Hayes, PharmD (Emailed: 1/3/2015) (Updated: 1/3/2015)
Click here to contact Bryan Hayes, PharmD

Does IV magnesium have a role in the management of acute migraine headache in the ED? A new study says yes. [1]


  • 35 patients received IV magnesium 1 gm over 15 minutes.
  • 35 patients received IV dexamethasone 8 mg + IV metoclopramide 10 mg over 15 minutes.
  • Each group contained men and women.
  • Initial pain score 8.2 in dexamethasone/metoclopramide group vs. 8.0 in magnesium group.

What They Found

Magnesium sulfate was more effective in decreasing pain severity at 20-min (pain scale 5.2 vs. 7.4) and 1-h (2.3 vs. 6.0) and 2-h (1.3 vs. 2.5) intervals after treatment (p < 0.0001) compared to treatment with dexamethasone/metoclopramide.

Application to Clinical Practice
Two previous studies found mixed results using magnesium. [2, 3] This new study found that IV magnesium may be an additional option. The authors didn't compare magnesium to more common treatments such as prochlorperazine or metoclopramide 20 mg (+/- ketorolac and diphenhydramine), which may limit its generalizability. However, magnesium's pain lowering effect was good regardless of comparator group.
Another possible use for magnesium in the ED?

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Category: Pharmacology & Therapeutics

Title: Is that IV antibiotic dose before ED discharge really necessary?

Keywords: antibiotic, IV, diarrhea (PubMed Search)

Posted: 11/25/2014 by Bryan Hayes, PharmD (Emailed: 12/6/2014) (Updated: 12/6/2014)
Click here to contact Bryan Hayes, PharmD

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. [1] One-time doses of vancomycin for SSTI before ED discharge are also not recommended (see Academic Life in EM post).

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. 

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Category: Pharmacology & Therapeutics

Title: Penicillin-Cephalosporin Cross-Reactivity Made Easy

Keywords: penicillin, cephalosporin, allergy, cross-reactivity (PubMed Search)

Posted: 10/7/2014 by Bryan Hayes, PharmD (Emailed: 11/1/2014) (Updated: 11/4/2014)
Click here to contact Bryan Hayes, PharmD

The cross-reactivity between cephalosporins and penicillins is significantly lower than the 10% figure many of us learned. In fact, the beta-lactam ring is rarely involved. So, when the warning pops up next time you order ceftriaxone in a penicillin-allergic patient, what should you do?

In a patient with a documented penicillin allergy, here is a simple chart to help determine when a cephalosporin is ok to use:


Common penicillins and cephalosporins with similar side chains include ampicillin/amoxicillin and cephalexin, cefaclor, cephadroxil, and cefprozil.

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Category: Pharmacology & Therapeutics

Title: Beta-Lactams in Critically Ill Patients: Current Dosing May be Inadequate

Keywords: beta-lactam, piperacillin/tazobactam, critically ill (PubMed Search)

Posted: 9/27/2014 by Bryan Hayes, PharmD (Emailed: 10/4/2014) (Updated: 10/4/2014)
Click here to contact Bryan Hayes, PharmD

Beta-lactam antimicrobials (penicillins, cephalosporins, and carbapenems) are frequently used for empiric and targeted therapy in critically ill patients. They display time-dependent killing, meaning the time the antibiotic concentration is above the minimin inhibitory concentration (MIC) is associated with improved efficacy.

Two new pharmacodynamic/pharmacokinetic studies suggest that current beta-lactam antimicrobial dosing regimens may be inadequate.

  • In patients from 68 ICUs across 10 countries, use of intermittent infusions (compared to extended and continuous infusions) and increasing creatinine clearance were risk factors for MIC target non-attainment. [1]
  • A second group specifically investigated the pulmonary penetration of piperacillin/tazobactam in critically ill patients and found that intrapulmonary exposure is highly variable and unrelated to plasma exposure and pulmonary permeability. [2]

Antimicrobial dosing in critically ill patients is complex. Current dosing of beta-lactams may be inadequate and needs to be studied further with relation to clinical outcomes.

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Category: Pharmacology & Therapeutics

Title: Pre-Exposure Prophylaxis (PrEP) for Preventing HIV Infection

Keywords: HIV, Pre-Exposure Prophylaxis, PrEP (PubMed Search)

Posted: 8/30/2014 by Bryan Hayes, PharmD (Emailed: 9/6/2014) (Updated: 9/6/2014)
Click here to contact Bryan Hayes, PharmD

In May 2014, the U.S. Public Health Service released the first comprehensive clinical practice guidelines for PrEP.

Pre-Exposure Prophylaxis (PrEP) has been shown to decrease the risk of HIV infection in people who are at high risk by up to 92%, if taken consistently.

How this applies to the ED patient:

  • You may start seeing more patients on only one HIV medication. The PrEP recommendation is once daily emtricitabine/tenofovir (Truvada) 200/300 mg. 
  • This is not a therapy that should generally be initiated in the ED as close outpatient monitioring and follow up is essential.

For more information, the CDC has a comprehensive website dedicated to PrEP.

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Category: Pharmacology & Therapeutics

Title: Is High-Dose Oseltamivir (Tamiflu) Indicated for Critically Ill Patients?

Keywords: oseltamivir, critically ill, high-dose, influenza, Tamiflu (PubMed Search)

Posted: 7/28/2014 by Bryan Hayes, PharmD (Emailed: 8/2/2014) (Updated: 8/2/2014)
Click here to contact Bryan Hayes, PharmD

Despite the lack of strong evidence to support the recommendation, the severity of the 2009 influenza pandemic prompted the World Health Organization (WHO) to advise that higher doses of oseltamivir (150 mg twice daily) and longer treatment regimens (> 5 days) should be considered when treating severe or progressive illness.

So, does the data support higher dosing in critically ill influenza patients?

A new systematic review concluded that "the small body of literature available in humans does not support routine use of high-dose oseltamivir in critically ill patients."

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Category: Pharmacology & Therapeutics

Title: Clindamycin's Role in Skin and Soft Tissue Infections

Keywords: clindamycin, MRSA, SSTI (PubMed Search)

Posted: 7/1/2014 by Bryan Hayes, PharmD (Emailed: 7/5/2014) (Updated: 7/5/2014)
Click here to contact Bryan Hayes, PharmD

Clindamycin used to be a first-line agent for many SSTIs, particularly where MRSA was suspected. With growing resistance to staph species, the 2014 IDSA Guidelines recommend clindamycin as an option only in the following situations:

  • Nonpurulent SSTI (primarily strep species)
    • Mild - oral clindamycin
    • Moderate - IV clindamcyin
    • Severe, necrotizing infections - adjunctive clindamycin only with suspected or culture-confirmed strep pyogenes
  • Purulent SSTI (primarily staph species)
    • Clindamycin only recommended in moderate or severe cases if cultures yield MSSA

* Clindamycin may be used if clindamycin resistance is <10-15% at the institution.

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Category: Pharmacology & Therapeutics

Title: Predictors of Failure of Outpatient Antibiotics for ED Cellulitis Patients

Keywords: cellulitis, antibiotic, outpatient (PubMed Search)

Posted: 5/31/2014 by Bryan Hayes, PharmD (Emailed: 6/7/2014) (Updated: 8/15/2014)
Click here to contact Bryan Hayes, PharmD

In a prospective cohort of 598 ED patients, 5 risk factors were independently associated with uncomplicated cellulitis patients who fail initial antibiotic therapy as outpatients and require a change of antibiotics or admission to hospital

  1. Fever (temperature > 38°C) at triage (OR = 4.3, 95% CI = 1.6 to 11.7)
  2. Chronic leg ulcers (OR = 2.5, 95% CI = 1.1 to 5.2)
  3. Chronic edema or lymphedema (OR = 2.5, 95% CI = 1.5 to 4.2)
  4. Prior cellulitis in the same area (OR = 2.1, 95% CI = 1.3 to 3.5)
  5. Cellulitis at a wound site (OR = 1.9, 95% CI = 1.2 to 3.0)

Patients presenting with uncomplicated cellulitis and any of these risk factors may need to be considered for observation +/- IV antibiotics.

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Category: Pharmacology & Therapeutics

Title: New Data - Dexmedetomidine as Adjunctive Therapy for Ethanol Withdrawal: An RCT

Keywords: dexmedetomidine, alcohol, ethanol, withdrawal (PubMed Search)

Posted: 4/28/2014 by Bryan Hayes, PharmD (Emailed: 5/3/2014) (Updated: 5/3/2014)
Click here to contact Bryan Hayes, PharmD

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 on the Academic Life in EM blog.

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.

Take Home Points

  1. Dexmedetomidine reduced short-term benzodiazepine requirements, but not long-term when using symptom-triggered approach.
  2. Monitor for bradycardia when using dexmedetomidine.

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Category: Pharmacology & Therapeutics

Title: Acetaminophen the villain of 2013

Keywords: Tylenol, liver faliure (PubMed Search)

Posted: 4/6/2014 by Brian Corwell, MD (Emailed: 4/27/2014) (Updated: 4/27/2014)
Click here to contact Brian Corwell, MD

Acetaminophen spent much of 2013 being chased by paparazzi and sharing magazine covers with Miley Cyrus. What a fall from stardom after becoming known as the pain reliever “hospitals use most,” and the one, “recommended by pediatricians.” Slogans we know well based on $100 million/year spent on advertising.

Approximately 150 patients a year die from unintentional acetaminophen poisoning averaged over the past 10 years. From 2001 to 2010, annual acetaminophen-related deaths amounted to about twice the number attributed to all other over-the-counter pain relievers combined, 

The FDA sets the maximum recommended daily dose of acetaminophen at 4 grams, or eight extra strength acetaminophen tablets.

Ingestion of 150 mg/kg or approximately 10g for a 70 mg individual reaches the toxic threshold for a single ingestion. The toxic threshold decreases in cases of chronic ingestion.

Patients who “unintentionally” overdose have been found to take just over 8g per day (almost double the recommended maximum).  This is unlikely due to taking one extra 325mg tablet once or twice.

Before we all go on a mad NSAID prescribing binge, let's all be aware of the dangers, educate our patients and allow Acetaminophen to walk the red carpet again.


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Category: Pharmacology & Therapeutics

Title: New Data: Azithromycin and Levofloxacin and Cardiovascular Risk

Keywords: azithromycin, levofloxacin, cardiovascular risk, mortality, dysrhythmia (PubMed Search)

Posted: 3/24/2014 by Bryan Hayes, PharmD (Emailed: 4/5/2014) (Updated: 4/5/2014)
Click here to contact Bryan Hayes, PharmD

A new study of almost 2 million prescriptions in VA patients compared the risk of cardiovascular death or dysrhythmia in patients receiving azithromcyin, levofloxacin, and amoxicillin.

What they found

Compared with amoxicillin, azithromycin was associated with a significant increase in mortality (HR = 1.48; 95% CI, 1.05-2.09) and dysrhythmia risk (HR = 1.77; 95% CI, 1.20-2.62) on days 1 to 5, but not 6 to 10.

Levofloxacin was associated with an increased risk throughout the 10-day period. Days 1-5 mortality (HR = 2.49, 95% CI, 1.7-3.64) and serious cardiac dysrhythmia (HR = 2.43, 95% CI, 1.56-3.79). Days 6-10 mortality (HR = 1.95, 95% CI, 1.32-2.88) and dysrhythmia (HR = 1.75; 95% CI, 1.09-2.82).

Important limitations

This study did not have a comparator group of patients getting no antibiotics. Previous data suggest patients on any antibiotic (eg, penicillin) have a higher risk of death or dysrhythmia.

The supplemental index shows that patients receiving azithromycin and levofloxacin had more serious infections (eg, PNA, COPD, etc.) which may have put them at higher risk for worse outcome irrespective of antibiotic choice.

What it means

It seems azithromycin and levofloxacin may contribute to a small increase in cardiovascular mortality and dysrhythmia during their use. A previous study found this is more likely in those with existing cardiovascular disease.

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  • Naloxone has technically always been able to be prescribed by physicians to individual patients.
  • New laws however, make it acceptable for prescribers in many states to prescribe naloxone to “third parties,” e.g parents, friends, etc. of patients, with the assumption that the overdosed patient will not be capable of administering the antidote to themselves.
  • Many states are offering short 10-20 minute training sessions on how bystanders can administer the reversal agent to the patient who has overdosed.
  • If prescribed, it should be prescribed to the individual who completed the training, not the intended patient, and may be written for intranasal or intramuscular administration.
  • Intranasal (IN) is “off label” and an approved intranasal preparation is not commercially available, but the intramuscular preparation can be prescribed along with an atomizer device. The usual IN dose is 1 mg per nostril which may be repeated in 3-5 minutes.

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Category: Pharmacology & Therapeutics

Title: Meningitis? Check the medication list!

Keywords: aseptic meningitis,antibiotics,sulfamethoxazole,valacyclovir,antiepileptics,levetiracetam (PubMed Search)

Posted: 3/6/2014 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD


Aseptic meningitis is meningitis with negative bacterial cultures. Overall, viral infections are the most common etiology, however medications can also cause this illness.

Well known causes of aseptic meningitis include: antimicrobials (particularly sulfamethoxazole/trimethoprim), NSAIDS, antivirals (valacyclovir), and antiepileptics.

Recently an abstract was published that suggests that patients on levetiracetam have a higher risk of developing aseptic meningitis than those on topiramate and gabapentin. Lamotrigine has also been implicated, but appears to have a lower risk than levetiracetam, topiramate and gabapentin.

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