Category: Pharmacology & Therapeutics
Keywords: Tranexamic acid, trauma, CRASH-2 (PubMed Search)
Posted: 1/2/2014 by Ellen Lemkin, MD, PharmD
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Tranexamic acid (TXA) is an antifibrinolytic that prevents clot breakdown by inhibiting plasminogen activation and plasmin activity
The CRASH-2 trial enrolled 20,211 adult trauma patients with significant hemorrhage (SBP <90 or HR 110) or at significant risk of hemorrhage
Patients were randomized to 1 gram TXA over 10 minutes followed by an infusion of 1 gm over 8 hours vs placebo
There was a significant reduction in the relative risk off all cause mortality of 9% (14.5% vs 16%, RR 0.91, CI 0.85-0.97, p = 0.0035)
The patients that benefited most were those most severely injured, and in those treated in less than 3 hours of injury.
1. CRASH-2 Trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomized, placebo controlled trial. The Lancet. 2010; 376:23-32.
2. Cap AP, Baer DG, Orman JA, Aden J, Ryan K, Blackbourne LH, Ryan K. Tranexemic Acid for Trauma Patients: A Critical Review of the Literature. Journal of Trauma, Injury, Infection and Critical Care. July 2011 Vol 71(1):S9-S14.
Category: Pharmacology & Therapeutics
Keywords: Hypertension, treatment (PubMed Search)
Posted: 12/21/2013 by Michael Bond, MD
(Updated: 2/17/2025)
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JNC8 (the Eigth Joint National Commission) released their recommendations for blood pressure management this week. The full article as published in JAMA can be found at http://jama.jamanetwork.com/article.aspx?articleid=1791497
Highlights from this report are
General Pearl: Remember to be cautious in acutely lowering the blood pressure in asymptomatic patients. Acute lowerings can cause watershed ischemia leading to strokes.
Category: Pharmacology & Therapeutics
Keywords: healthcare-associated pneumonia, HCAP, atypical, macrolide, fluoroquinolone (PubMed Search)
Posted: 12/2/2013 by Bryan Hayes, PharmD
(Updated: 12/7/2013)
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In a potentially ground breaking study of healthcare-associated pneumonia (HCAP) patients, atypical pathogens were identified in 10% of cases!
Application to clinical practice: Add atypical coverage with a macrolide or respiratory fluoroquinolone for HCAP patients who have been in the community for any length of time.
The study also identified HCAP patients who may not require 3 'big gun' broad-spectrum antibiotics. This is a practice changing article for ED providers. For more analysis of the study, please note the bonus reading links below.
Bonus reading:
Dr. Emily Heil (@emilylheil) analyzes the full study in more depth at Academic Life in Emergency Medicine: http://academiclifeinem.com/new-treatment-strategy-not-so-sick-health-care-associated-pneumonia/
Dr. Ryan Radecki (@emlitofnote) critiques the study at Emergency Medicine Literature of Note: http://www.emlitofnote.com/2013/10/down-titrating-antibiotics-for-hcap.html
Maruyama T, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective mulitcenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis 2013;57(10):1373-83. [PMID 23999080]
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Category: Pharmacology & Therapeutics
Keywords: oral anticoagulant,edoxaban,atrial fibrillation,stroke,Xa (PubMed Search)
Posted: 12/5/2013 by Ellen Lemkin, MD, PharmD
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It has linear, predictable pharmacokinetics, achieves maximal concentration within 1-2 hours, is 50% renally excreted, and has a half life is 9-11 hours.
Edoxaban was evaluated in a recent trial comparing warfarin in patients with atrial fibrillation.
The primary end point or first stroke or systemic pulmonary embolic event occurred in 1.5% with warfarin, compared with 1.18% in the high dose edoxaban (HR 0.79; 97.5% CI 0.63-0.99, P<0.001). In the intention to treat there were trends favoring high dose edoxaban and unfavorable trends with the lower dose.
The principal safety end point of major bleeding occurred in 3.43% with warfarin versus 2.75% with high dose edoxaban (HR 0.86; 95% CI 0.71-0.91, P<0.001).
Bottom line: Both high dose (60 mg) and low dose (30 mg) edoxaban were non-inferior to warfarin with prevention of stroke or systemic emboli, and were associated with significantly lower rates of bleeding and death from cardiovascular causes.
Currently it is approved for use in Japan.
Edoxaban versus Warfarin in Patients with Atrial Fibrillation. Giuliano, RP et al. NEJM Nov 28, 2013; 369(22):2093-2104.
Category: Pharmacology & Therapeutics
Keywords: Cephalosporin,penicillin,anaphylaxis,urticaria,cross sensitivity (PubMed Search)
Posted: 11/7/2013 by Ellen Lemkin, MD, PharmD
(Updated: 2/17/2025)
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When patients with severe allergies to penicillin (urticarial, bronchospasm, anaphylaxis, angioedema) are excluded, the cross reactivity to cephalosporins is very low (approximately 0.1%)
The reaction is related to structures in the side chain, not the cyclical structure as thought in the past.
There are several cephalosporins with IDENTICAL side chains that should not be given to patients with allergies to specific penicillins, namely:
The Medical Letter on Drugs and Therapeutics • December 24, 2012 (Issue 1406) p. 101.
Category: Pharmacology & Therapeutics
Keywords: contrast-induced nephropathy, n-acetylcysteine, NAC (PubMed Search)
Posted: 10/31/2013 by Bryan Hayes, PharmD
(Updated: 11/2/2013)
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A recent meta-analysis has called into question whether contrast-induced AKI even occurs after an IV dye load for radiologic imaging. [1] This conclusion is most certainly up for debate.
Irrespective of that conclusion, prevention of contrast-induced nephropathy is still important. Is there any benefit to using N-acetylcysteine over normal saline in the ED? Probably not according to a new study. [2]
Conclusions
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Category: Pharmacology & Therapeutics
Keywords: cryptococcal, meningitis, amphotericin, flucytosine (PubMed Search)
Posted: 9/25/2013 by Bryan Hayes, PharmD
(Updated: 10/5/2013)
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Treatment of patients with HIV/AIDS can frequently mean consideration for, and need to treat cryptoccocal meningitis.
Since 1997, studies have demonstrated that high-dose Amphotericin B combined with flucytosine has improved outcomes compared to low dose treatment or monotherapy.
A recent 2013 study reiterated this approach, showing significant decrease in deaths at 70 days post-treatment and increased rates of yeast clearance with combination therapy of Amphotericin B plus flucytosine.
Recommendation:
Antifungal treatment of cryptococcal meningitis should start with Amphotericin B at 0.7-1 mg/kg IV daily plus concurrent flucytosine 25 mg/kg orally q6 hours. Fluconazole can be substituted in place of flucytosine if it is not available or not tolerated.
Category: Pharmacology & Therapeutics
Keywords: procainamide,atrial fibrillation,prolonged QT,monomorphic VT (PubMed Search)
Posted: 10/3/2013 by Ellen Lemkin, MD, PharmD
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ACLS recommendation for procainamide in tachycardic rhythms is:
Loading dose 20 mg/minute (up to 50 mg/minute for more urgent situations) until:
Maintenance infusion is 1 to 4 mg/min.
An easier method for dosing acute onset atrial fibrillation in stable patients was used in the Ottawa Aggressive Protocol, in which they administered 1 gm over 60 min, which was interrupted if BP < 100 mmHg; if corrected by a 250 ml IV bolus, the infusion was resumed. This was not used, however if the patient was to be admitted.
A strategy for treating stable monomorphic VT with procainamide used:
100 mg IV over 1-2 minutes, repeat as necessary until an endpoint of
If no slowing of the tachycardia occurred with a dose of 400 mg, the administration was ceased.
1. Steil IG, Clement CM, Perry JJ et al. Association of the Ottawa Aggressive Protocol with rapid discharge of emergency department patients with recent-onset atrial fibrillation or flutter. CJEM 2010;12(3):181-91.
2. Komura S, Chinushi M, Furushima H. et al. Efficacy of Procainamide and Lidocaine in Terminating Sustained Monomorphic Ventricular Tachycardia. Circulation May 2010 Vol 72
Category: Pharmacology & Therapeutics
Keywords: antibiotic, obese, obesity, critically ill, antimicrobial (PubMed Search)
Posted: 8/31/2013 by Bryan Hayes, PharmD
(Updated: 9/7/2013)
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Although there is a paucity of data to guide dosing of antimicrobials in the critically ill obese patient, we can draw some conclusions from existing kinetic studies. Assuming normal renal and hepatic function, here's what to do:
Penicillins: Use the high end of dosing range. For example, if the plan is to use piperacillin/tazobactam 3.375 gm IV every 6 hours for a complicated intra-abdominal infection, use 4.5 gm instead.
Cephalosporins: Use the high end of the dosing range.
Carbapenems: Use the high end of the dosing range.
Quinolones: Use the high end of the dosing range.
Aminoglycosides: Dose using adjusted body weight. ABW (kg) = IBW + 0.4 X (actual body weight - IBW)
Vancomycin: 15-20 mg/kg actual body weight every 8 to 12 hours. Adjust based on trough level.
When dosing most antibiotics in critically ill obese patients, use the high end of the dosing range (if not more).
Erstad BL. Dosing of medications in morbidly obese patients in the intensive care unit setting. Intensive Care Med 2004;30(1):18-32. [PMID 14625670]
Medico CJ, Walsh P. Pharmacotherapy in the critical ill obese patient. Crit Care Clin 2010;26(4):679-88. [PMID 20970057]
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Category: Pharmacology & Therapeutics
Keywords: fluid, saline, chloride (PubMed Search)
Posted: 7/22/2013 by Bryan Hayes, PharmD
(Updated: 8/2/2013)
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A recent review identified 5 key points to consider when prescribing fluids.
Raghunathan K, et al. Fluids are drugs: type, dose and toxicity. Curr Opin Crit Care 2013;19(4):290-8. [PMID 23817025]
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Category: Pharmacology & Therapeutics
Keywords: pain, hydromorphone (PubMed Search)
Posted: 7/3/2013 by Bryan Hayes, PharmD
(Updated: 7/6/2013)
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A recent, randomized study evaluated two approaches for treating acute pain in an inner-city ED.
Application to clinical practice: For most patients with acute, severe pain in the ED, start with hydromorphone 1 mg. It may be all the patient needs and can potentially avoid giving them extra opioid they don't need.
Chang AK, et al. Randomized clinical trial of the 2 mg hydromorphone bolus protocol versus the "1 + 1" hydromorphone titration protocol in treatment of acute, severe pain in the first hour of emergency department presentation. Ann Emerg Med. 2013 May 16. [Epub ahead of print]. PMID 23694801
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Category: Pharmacology & Therapeutics
Keywords: insulin, metformin, sulfonylureas, repaglinide (PubMed Search)
Posted: 7/4/2013 by Ellen Lemkin, MD, PharmD
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Diabetes. Pharmacist's Letter March 2013;29(3):13-4.
Category: Pharmacology & Therapeutics
Keywords: cellulitis, cephalexin, sulfamethoxazole/trimethoprim, Bactrim, streptococcus (PubMed Search)
Posted: 5/20/2013 by Bryan Hayes, PharmD
(Updated: 5/31/2013)
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Background
In the current era of community-acquired MRSA (CA-MRSA), most of our outpatient treatment options for cellulitis aim to cover MRSA. Choices include sulfamethoxazole/trimethoprim (SMZ-TMP), doxycycline, linezolid, and clindamycin (depending on local susceptibility patterns).
A New Study
Take Home Clinical Points
Pallin DJ, et al. Clinical Trial: Comparative Effectiveness of Cephalexin Plus Trimethoprim-Sulfamethoxazole Versus Cephalexin Alone for Treatment of Uncomplicated Cellulitis: A Randomized Controlled Trial. Clinical Infectious Diseases 2013;56(12):1754-62. [PMID 23457080]
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Category: Pharmacology & Therapeutics
Keywords: phosphate, fosphenytoin, phenytoin, hyperphosphatemia (PubMed Search)
Posted: 4/29/2013 by Bryan Hayes, PharmD
(Updated: 5/2/2013)
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Introduction
Fosphenytoin is a prodrug and is metabolized quickly to phenytoin after administration. The conversion of fosphenytoin to phenytoin involves the release of phosphate. In fact, each mmol of fosphenytoin releases 1 mmol of phosphate.
Clinical Question
Are patients at risk for hyperphosphatemia after fosphenytoin loading?
Data
There are only two cases of reported hyperphosphatemia.
Bottom Line
Despite the phosphate load from fosphenytoin administration, hyperphosphatemia is very rare and probably associated with renal insufficiency and dosing errors.
McBryde KD, et al. Hyperphosphatemia due to fosphenytoin in a pediatric ESRD patient. Pediatr Nephrol. 2005;20(8):1182-5. [PMID 15965770]
Rose R, et al. Fosphenytoin-induced bradyasystole arrest in an infant treated with charcoal hemofiltration [abstract]. J Toxicol Clin Toxicol. 1998;36:473.
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Category: Pharmacology & Therapeutics
Keywords: Prothrombin Complex Concentrate, warfarin, coumadin, vitamin K antagonist, anticoagulant, PCC (PubMed Search)
Posted: 5/2/2013 by Ellen Lemkin, MD, PharmD
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Approval of Kcentra™ may open the door for studying treatment of the bleeding patient on newer oral anticoagulants.
Category: Pharmacology & Therapeutics
Keywords: alteplase, tPA, dabigatran, anticoagulant, apixaban, rivaroxaban (PubMed Search)
Posted: 4/3/2013 by Bryan Hayes, PharmD
(Updated: 4/5/2013)
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A new recommendation in the 2013 Ischemic Stroke Guidelines provides guidance on what to do in patients taking new oral anticoagulants who are deemed eligible for IV fibrinolysis. Here is what the guidelines say:
Until further data are available, a history consistent with recent use of new oral anticoagulants generally precludes use of IV tPA.
Jauch EC, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44(3):870-947. PMID 23370205
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Category: Pharmacology & Therapeutics
Keywords: Status epilepticus, Keppra, seizures, valproic acid, levetiracetam (PubMed Search)
Posted: 4/4/2013 by Ellen Lemkin, MD, PharmD
(Updated: 2/17/2025)
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Trinka E. What is the evidence to use new intravenous AED in status epilepticus? Epilepsia 2011 52(Suppl 8):35-8.
Zelano J, Kumlien E. Levetiracetam as alternative stage two antiepileptic drug in status epilepticus: A systematic review. Seizure 2012. 21:233-6.
Category: Pharmacology & Therapeutics
Keywords: Statins, Acute Coronary Syndrome, Myocardial Infarction (PubMed Search)
Posted: 3/7/2013 by Ellen Lemkin, MD, PharmD
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Statins for acute coronary syndrome. Cochrane Database of Systemic Reviews. Volume 9, 2011.
Category: Pharmacology & Therapeutics
Keywords: ischemic stroke, hypertension, blood pressure (PubMed Search)
Posted: 2/25/2013 by Bryan Hayes, PharmD
(Updated: 3/2/2013)
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The newest iteration of 'Guidelines for the Early Management of Patients with Acute Ischemic Stroke' was recently published. Here are the key revisions specific to blood pressure management:
If administering rtPA, blood pressure needs to be <185/110 mm Hg. That recommendation didn't change.
Jauch EC, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013 Jan 31 [Epub ahead of print]. PMID 23370205.
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Category: Pharmacology & Therapeutics
Keywords: lidocaine, intraosseus, IO (PubMed Search)
Posted: 1/2/2013 by Bryan Hayes, PharmD
(Updated: 2/2/2013)
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Intraosseus (IO) access has become quite popular in critically ill patients requiring immediate resuscitation. In a patient responsive to pain, however, pain and discomfort is associated with the force of high-volume infusion through the established line.
Before flushing the line, consider administering preservative-free 2% lidocaine (without epinephrine) for patients responsive to pain prior to flush.
The suggested dose is 20-40 mg (1-2 mL) of the 2% lidocaine, followed by the 10 mL saline flush.
If preservative-free 2% lidocaine is not stocked in your ED, now is the time to consider adding it.
Fowler RL, Pierce, Nazeer S, et al. Powered intraosseous insertion provides safe and effective vascular access for emergency patients. Ann Emerg Med 2008;52(4):S152.
Ong MEH, Chan YH, Oh JJ, et al. An observational, prospective study comparing tibial and humeral intraosseus access using EZ-IO. Am J Emerg Med 2009;27(1):8-15. [PMID 19041528]
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