UMEM Educational Pearls - Pharmacology & Therapeutics

A new guideline for convulsive status epilepticus in adults AND children was recently published. [1] An insightful commentary was published alongside it (both are open access). [2] The proposed algorithm is below. Here are a few additional points to note:

  • The guideline applies to convulsive status epilepticus.
  • A new level of evidence rating of "U" is utilized. It means "data inadequate or insufficient; give current knowledge, treatment is unproven."
  • It addresses 5 specific questions:
    • Which anticonvulsants are efficacious as initial and subsequent therapy?
    • What adverse events are associated with anticonvulsant therapy?
    • Which is the most effective benzodiazepine?
    • Is IV fosphenytoin more effective than IV phenytoin?
    • When does anticonvulsant efficacy drop significantly?
  • IM midazolam is incorporated as one of the recommended 1st choices of treatment.
  • One of the second phase therapy recommendations is levetiracetam 60 mg/kg! It is a level U recommendation. Be prepared for neurology to request this dose. There is no data in adults to support this high of a dose.

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Category: Pharmacology & Therapeutics

Title: Does Succinylcholine Increase Mortality in Severe TBI Patients?

Keywords: succinylcholine, rocuronium, mortality, traumatic brain injury, RSI (PubMed Search)

Posted: 2/4/2016 by Bryan Hayes, PharmD (Emailed: 2/6/2016) (Updated: 2/6/2016)
Click here to contact Bryan Hayes, PharmD

An interesting new study was published looking at in-hospital mortality in TBI patients who received succinylcholine or rocuronium for RSI in the ED.

What They Did

  • Retrospective cohort study
  • 233 patients (149 received succinylcholine, 84 received rocuronium)
  • Groups were well matched overall (roc group was older, more hypotension in sux group)
  • Within the two groups, patients were separated based on head Abbreviated Injury Score (scores of 4 or 5 were considered severe)
  • The authors controlled for a lot of confounding factors

What They Found

  • Overall, mortality was the same in each group (23%)
    • Mortality within the roc group was the same irrespective of head AIS
    • Mortality within the sux group was significantly higher in the subset of patients with higher head AIS (OR 4.1, 95% CI 1.18-14.12, p = 0.026)

Application to Clinical Practice

  • Succonylcholine may increase mortality in severe TBI patients undergoing RSI in the ED compared to rocuronium
  • The confidence interval was wide and these findings need to be confirmed in a prospective study
  • Though the patients were well matched and the authors controlled for many variables, it still is difficult to pinpoint one intervention as the cause for mortality in critically ill patients (eg, etomidate + sepsis)
  • With proper rocuronium dosing, intubating conditions are similar to succinylcholine. So if there is a potential for increased mortality in severe TBI patients with sux, rocuronium seems to provide a safer alternative.

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Category: Pharmacology & Therapeutics

Title: Sugammadex for Reversal of Non-Depolarizing Neuromuscular Blockers

Keywords: sugammadex, rocuronium, NMBA, vecuronium (PubMed Search)

Posted: 12/29/2015 by Bryan Hayes, PharmD (Emailed: 1/2/2016) (Updated: 1/2/2016)
Click here to contact Bryan Hayes, PharmD

After three failed attempts, the FDA finally granted approval for Merck's non-depolarizing neuromuscular blocker reversal agent sugammadex (Bridion). Though the product has been used in Europe and Asia for several years, hypersensitivity concerns led to the delayed approval in the U.S.

Important points

  1. Reverses rocuronium, vecuronium, and to a lesser degree, pancuronium
  2. Full reversal obtained about 3 minutes after administration
  3. Eliminated entirely by the kidneys in about 8 hours (6 times longer in patients with CrCl < 30 mL/min)
  4. Dosing is generally 2-4 mg/kg. Total body weight should be used in obese patients

Application to Clinical Practice

  1. Potential for use in situations where a neuro exam is needed shortly after intubation (eg, status epilepticus, ICH)
  2. The risk of serious hypersensitivity appears to be < 1% in published literature
  3. Cost will most assuredly be high
  4. Long duration in patients with reduced kidney function means further attempts to re-paralyze with roc, vec, or pancuronium may be unsuccessful

The EM PharmD blog discusses sugammadex's approval in more detail.

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Category: Pharmacology & Therapeutics

Title: Therapeutic Tramadol Use Significantly Increases Seizure Risk

Keywords: tramadol, seizure (PubMed Search)

Posted: 12/3/2015 by Bryan Hayes, PharmD (Emailed: 12/5/2015) (Updated: 7/6/2016)
Click here to contact Bryan Hayes, PharmD

Tramadol has a reputation for being a safe, non-opioid alternative to opioids. Nothing could be further from the truth. Several blogs have published about the dangers of tramadol:

But what about seizure risk? Previous studies have been unable to confirm an increased seizure risk with therapeutic doses of tramadol (Seizure Risk Associated with Tramadol Use from EM PharmD blog). However, a new study refutes that premise.

22% of first-seizure patients had recent tramadol use!

  1. Mean total tramadol dose in last 24 hours (reported): 140 mg
  2. Duration of tramadol use less than 10 days: 84.5%
  3. Seizure within 6 hours of tramadol consumption: 74%

This was a retrospecitve study without laboratory confirmation of tramadol intake. Nevertheless, it behooves us not to think of tramadol as a safer alternative to opioids. It is an opioid after all, and it comes with significant adverse effects.

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Category: Pharmacology & Therapeutics

Title: Avoid Opioids for Low Back Pain

Keywords: low back pain, opioids, naproxen, oxycodone, cyclobenzaprine (PubMed Search)

Posted: 10/21/2015 by Bryan Hayes, PharmD (Emailed: 11/7/2015) (Updated: 11/7/2015)
Click here to contact Bryan Hayes, PharmD

If there weren't enough reasons to avoid opioids, here is another: opioids don't work for low back pain (LBP).

Objective

A well-done, double-blind, randomized controlled trial from JAMA set out to compare functional outcomes and pain at 1 week and 3 months after an ED visit for acute LBP among patients randomized to a 10-day course of (1) naproxen + placebo; (2) naproxen + cyclobenzaprine; or (3) naproxen + oxycodone/acetaminophen.

Intervention

  • Nontraumatic, nonradicular LBP of 2 weeks’ duration or less
  • All patients were given 20 tablets of naproxen, 500 mg, to be taken twice a day.
    • They were randomized to receive either 60 tablets of placebo; cyclobenzaprine, 5 mg; or oxycodone, 5 mg/acetaminophen, 325 mg. Participants were instructed to take 1 or 2 of these tablets every 8 hours, as needed for LBP.
  • Patients received a standardized 10-minute LBP educational session prior to discharge.

Outcome

Neither oxycodone/acetaminophen nor cyclobenzaprine improved pain or functional outcomes at 1 week compared to placebo, and more adverse effects were noted.

Application to Clinical Practice

Among patients with acute, nontraumatic, nonradicular LBP presenting to the ED, avoid adding opioids or cyclobenzaprine to the standard NSAID therapy.

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Category: Pharmacology & Therapeutics

Title: Targeted Temperature Management's Effect on Drugs

Keywords: targeted temperature management, drug (PubMed Search)

Posted: 9/27/2015 by Bryan Hayes, PharmD (Emailed: 10/3/2015) (Updated: 10/3/2015)
Click here to contact Bryan Hayes, PharmD

An excellent new review article provides a detailed look at how the drugs we give are affected by targeted temperature management. Here is a helpful chart of drug alterations that have data in reduced body temperature states:

Other Important Points:

  1. Lingering effects of sedatives may confound prognostication and may even mimic brain death. Concentrations of remifentanil, propofol, and midazolam decrease during rewarming, whereas no change has been demonstrated for fentanyl, indicating that the pharmacokinetic alterations fentanyl incurs during induction and maintenance of hypothermia persist during and following the rewarming phase.
  2. Continuous infusions of analgesics, sedatives, and hemodynamic support agents may require closer monitoring and smaller incremental changes compared to normothermic states.
  3. The QTc interval is increased in TTM, though it has not been associated with an increased risk of torsades de pointes or in-hospital mortality.

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Category: Pharmacology & Therapeutics

Title: Ketamine vs. Morphine for Analgesia in the ED

Keywords: ketamine, analgesia, morphine, pain (PubMed Search)

Posted: 8/30/2015 by Bryan Hayes, PharmD (Emailed: 9/5/2015) (Updated: 9/5/2015)
Click here to contact Bryan Hayes, PharmD

A new prospective, randomized, double-blind trial compared subdissociative ketamine to morphine for acute pain in the ED.

What they did

  • 45 patients received IV ketamine 0.3 mg/kg (mean baseline pain score 8.6)
  • 45 patients received IV morphine 0.1 mg/kg (mean baseline pain score 8.5)
  • Source of pain was abdominal for ~70% in each group
  • Exclusion criteria was pretty standard

What they found

  • Pain score at 30 minutes: 4.1 for ketamine vs. 3.9 for morphine (p = 0.97)
  • No difference in the incidence of rescue fentanyl analgesia at 30 or 60 minutes
  • No serious adverse events occurred in either group
  • Patients in the ketamine group reported increased minor adverse effects at 15 minutes post-drug administration
Application to clinical practice
  1. In an effort to reduce opioid use in the ED, low-dose ketamine may be a reasonable alternative to opioids for acute analgesia.
  2. State nursing regulations govern who can administer IV ketamine in the ED.
  3. What to prescribe on discharge? Lead author Dr. Motov recommends a "pain syndrome targeted" approach with "patient-specific opioid and non-opioid analgesics."

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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.

Caveats

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.

Notes:

  • 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]

Intervention

  • 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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