Monday, December 31, 2012

Who, Pharm.D.

Over the holiday, I began reading one of the William Osler biographies. While reading his inspiring and influential journey, which to this day continues to guide and lead others, I paused to reflect on my own profession. Although I’m searching for the pharmacy equivalent to such influential figures in medicine, our education methods are far more interesting.

Though books and lectures were a component of late 19th century and early 20th century medical education, Osler saw them more as tools opposed to staples.  Introducing “clerkships” to medical education in America, students were thrust into practice to study “…individuals – not diseases.”  No doubt, a reflection of the existing education of physicians in other countries during that time, but paving the way for todays education model and future directions (ie, Khan Academy, flipping the classroom, etc).

Pharmacy education on the other hand, lags behind. Specifically, in the amount of practical experience the average pharmacy student accumulates before graduation and the over reliance on lectures and textbooks. Just recently, more focus on pharmacy clerkships was implemented by increasing the required hours of practical experience.  Unfortunately, there are few teachers out there that can accommodate the vast class sizes of today’s schools of pharmacy.  Speaking from personal experience, one is left to either sit in the back of a pharmacy to ‘observe’ inappropriate habits of overwhelmed community pharmacists or be put to work counting and labeling.  Certainly, students with initiative can create their own learning opportunities, seeking volunteer clerkship with faculty, pursuing PGY1 and PGY2 residency, but similarly, the deficiency of opportunities lags behind the need of the students, and the profession.  The figure is in the neighborhood of 1 residency position for every 2 to 3 pharmacy students seeking a residency. Mind you, only about 20% of graduating pharmacists seek residency/post graduate training.

Pharmacy education needs to change, both prior to graduation and post graduation. Through the evolution of medical education led by pioneering figures, medicine itself has advanced remarkably over the past 120 years. Pharmacy education can do the same.  Pharmacy education must do the same. 

Since Doctor Who saved the universe from oblivion on Dec 21st (…cough, cough…), 2013 provides us, and the years to come, an opportunity to make a difference.  For me it is, among other things, the need for an evolution (perhaps a revolution) of pharmacy education.

“A difference, to be a difference, must make a difference.” –Gertrude Stein

Monday, December 24, 2012

Thursday, December 20, 2012

Tale of the Comeback Kid: Procainamide in the ED

It seems as though the traditional "go-to" management of atrial fibrillation in the setting of rapid ventricular response in the emergency department involves rate control and anticoagulation.

Can we break this tradition and consider alternative therapeutic management in certain subpopulations of patients with dysrhythmias?

Recently, there has been some discussion regarding the use of rhythm control for new-onset atrial fibrillation, particularly procainamide, which used to be used back in the day and has started to make a comeback.

You may ask why. Here's the story of the revived interest in the emergent use of procainamide in recent-onset atrial fibrillation as well as other dysrhythmias:

The Procainamide Comeback: Blasts from the Past and Hints for the Future
Conversion of recent-onset atrial fibrillation
Class Ia recommendation for our northern neighbors in Canada
·         One study demonstrated conversion rate of new-onset atrial fibrillation with the use of IV procainamide in nearly 52% of all patients.
·         Another study demonstrated 59.9% conversion rate in patients treated with IV procainamide using the Ottawa Protocol.
Wide-complex atrial fibrillation associated with Wolff-Parkinson-White (WPW) syndrome
Class I recommendation for management of atrial fibrillation in the setting of WPW as of 2011 ACCF/AHA/HRS guidelines
·         A review of various studies show amiodarone to not be the preferred treatment option for atrial fibrillation associated with WPW due to inducible proarrhythmias
·         Incidence was less with procainamide.
Stable monomorphic ventricular tachycardia
Class IIa recommendation (preferred over amiodarone [Class IIb]) based on 2010 AHA guidelines
·         One study demonstrated superiority of IV procainamide over IV lidocaine in terminating episodes of stable monomorphic ventricular tachycardia (79% versus 19%).

Interestingly enough, the Canadians seem to have a lot more to offer in terms of evidence surrounding the use of procainamide in the emergency department; perhaps we can adopt this practice more routinely when the situation arises.

To complete the preparation for the comeback of procainamide, let us now retrieve that vial sitting all the way in the back corner of the top shelf in your pharmacy and review the dosing just for kicks:

The loading dose of procainamide can be administered in a number of ways:
  • 20 to 50 mg/min IV OR 100 mg IV at a rate not exceeding 50 mg/min repeated every five minutes as needed to a total dose of 1 g
    • When a total of 500 mg has been given, one should wait ten minutes before continuing with administration to prevent profound hypotension.
  • Infusion of 17 mg/kg IV over one hour
    • In patients with renal dysfunction or congestive heart failure, loading dose should not exceed 12 mg/kg.
The maintenance dose of procainamide typically ranges between 1 and 4 mg/min administered via continuous IV infusion.

Procainamide is looking to redeem itself for use in the ED...are you up to the challenge?

Monday, December 17, 2012


Here is my attempt at a trick of the trade. This one is focused at the intubated STEMI patient in whom the EMS crew couldn’t get the 324mg of aspirin on board, and the cardiologist wants to load with clopidogrel 600mg as well as atorvastatin 80mg. Provided we can drop an OG tube before the patient gets sent to the cath-lab, this is how we get the meds into the patient:

Grab a Toomey Tip 60mL syringe, the meds, some water and something to crush the tablets (In our ED, commercial pill crushers disappear within a day, so we often use a blunt object located nearest t0 the pharmacy).

First, crush the tablets while still in the blister pack so fragments don’t go flying everywhere (easy to do with chewable aspirin, not so much with clopidogrel and atorvastatin).

Draw up about 25 mL of water into the syringe from the cup. While plugging the end of the Toomey tip with your thumb, remove the plunger of the syringe.

Dump the contents of the crushed tablet blister packs into the syringe through the opening created by the missing plunger.

Return the plunger into the syringe, and shake (Don’t take your thumb of the Toomey tip unless you want aspirin/Plavix/Lipitor shake all over the place).
Draw up some extra water (to a total of about 45-50mL).

If there are still some tablet fragments after administering, draw up an extra 25-30mL of water to flush.

Done and done.

Thursday, December 13, 2012

Mama Knows Best: Thrombolytic Therapy for MPE in the Pregnant Patient

My residency program director once made the following statement:

"Pregnancy is the worst STD that anyone can get."

At the time, I laughed when he said this, and I asked him to clarify this somewhat startling observation. We then had a brief discussion and came to the conclusion that pregnancy is associated with many comorbidities that otherwise would not typically occur in the non-pregnant patient. These include conditions of pregnancy that we commonly think of such as morning sickness and acid reflux disease. Diseases that are concerning for us clinicians practicing in the emergency department that pregnant patients may present with include diabetic ketoacidosis, preeclampsia and eclampsia, and thromboembolism.

This led me to wonder about the treatment of life-threatening thromboembolism, particularly massive pulmonary embolism (MPE), in the pregnant patient. We are familiar with the fact that pregnancy in and of it itself is a hypercoaguable state that puts patients at increased risk of thromboembolism. One of the worst-case scenarios I can envision is a young pregnant patient at 32 weeks' gestation presenting to the emergency department after a syncopal episode with the classical picture of MPE: acute dyspnea, sudden chest pain, and signs of hemodynamic instability with a blood pressure of 83/46 mmHg, respiratory rate of 33 bpm, heart rate of 120 bpm, and 80% oxygen saturation upon room air. EKG reveals sinus tachycardia and evidence of right ventricular strain. An emergent transthoracic 2D echocardiogram is performed, which reveals a grossly enlarged right ventricle with severe tricuspid regurgitation and impaired right ventricular function. A VQ scan is highly suspicious for MPE, and a CT scan of the thorax shows a large saddle embolus that extends from the right to the left pulmonary arteries, confirming the diagnosis of MPE.

The ED attending physician orders alteplase 100 mg IV to be infused over 2 hours for this patient. Upon seeing this order, you state something to the following effect:

"You want to use THAT in HER?? That's preposterous!!"

But is it?

We are aware that one of the relative contraindications of thrombolytic therapy is indeed pregnancy. You are faced with the fact that you now have two lives at stake here (mother and baby) in the setting of an MPE, with the caveat that the risk associated with the administration of thrombolytic therapy is bleeding that could be potentially life-threatening. So what is the best option here?

Much of the literature that exists regarding the use of thrombolytic therapy for the treatment of MPE in pregnancy originates primarily from case reports. In many of these studies, thrombolytic therapy has been shown to be successful in rapidly lysing pulmonary emboli with minimal maternal and/or fetal complications. The risk of maternal hemorrhage has been determined to be approximately 8%, occurring from the genitourinary tract and not secondary to intracranial hemorrhage. Any of the bleeding complications experienced by pregnant patients in these case reports were mostly associated with the administration of streptokinase, and there has been no reported evidence of maternal death. Fetal deaths and preterm deliveries that reportedly occurred in pregnant patients treated with thrombolytic therapy for MPE were secondary to the course of the disease itself and not deemed to be associated with treatment. In addition, an interesting case series demonstrated that both patients and their offspring did not have long-term complications associated with therapy at a two-year follow up period.

In terms of the choice of thrombolytic agent, it seems that alteplase would be the most ideal agent to use in this setting for now. Unlike urokinase, alteplase does not cross the placenta (although it is not clear whether this has any implications in inducing coagulopathy of the fetus). In addition, the "claim-to-fame" for alteplase when compared to streptokinase is the idea that the proposed incidence of immunogenic reactions is minimized (which has been previously discussed here). Perhaps there may be some interest in investigating the use of tenecteplase in pregnancy first, and then for the treatment of MPE in the setting of pregnancy, due to the fact that it can be given as an IV bolus with the added potential benefit of possessing a lower risk of bleeding compared to alteplase.

Although MPE is a difficult situation to manage, and even more so in the setting of pregnancy, there is no evidence to support the withholding of thrombolytic therapy in these patients. With two lives to potentially care for in this scenario, a rapid turnaround time can be expected with the administration of thrombolytic therapy that can salvage both the mother and baby. And as the saying goes, "Mama knows best."

Monday, December 10, 2012

Beware the Antibiogram

As I was preparing a post discussing antimicrobial double coverage, I was describing the utility of a hospital antibiogram in aiding in the selection empiric therapy.  Let’s just say I’m glad I have had teachers and mentors whose favorite question was “why.”  While trying to answer that simple question, I came across this article from 2007 [1] that did an excellent job describing the limitations of antibiograms. Although I was aware of certain limitations of antibiograms, I wasn’t aware they are essentially useless in the ED.

Generally, antibiograms are annually reported collections of antimicrobial susceptibilities of local pathogens for a given institution.  Guidance on the standardization and construction of antibiograms is provided by CLSI (things like not reporting duplicate isolates, not reporting data for fewer than 10 isolates of a single bacterial species, providing subgroup analyses of patient populations, etc). But despite these published guidelines, data outlined in this review describe few hospitals are actually following these recommendations. 

Unfortunately, this translates into most antibiograms being an aggregate of all pathogens isolated by the microbiology lab in a given year. As a result, several limitations to the broad utilization of the antibiogram emerge (particularly its usefulness as a guide to empiric antimicrobial selection).

Antibiograms do not take into consideration a patient’s infection history, past antimicrobial use and comorbidities. For instance, for Pseudomonas specifically, antibiograms do not describe differing susceptibility patters with FQs and AGs in patients with and without cystic fibrosis.  Likewise, it cannot be determined whether the Pseudomonas isolate was from lung, urine or skin.

Since the collection of pathogen susceptibilities is often reported as aggregate, specific pathogen data should not be generalized across an entire hospital and between different patient care units.   Trends in specific hospital units tend to be hidden (Acinetobacter outbreak in the ICU).

Data reported in antibiograms does not provide information concerning the timing of the isolate in relation to infection (community vs hospital acquired).  Similarly, it cannot be deciphered whether the pathogen reported in the antibiogram was causing infection or colonization nor can they reveal trends in cross-resistance to multiple antimicrobials. This may be the biggest limitation preventing utilization of this tool in the ED.  It’s great to know my institutions’ antibiogram reports 72% susceptibility of levofloxacin to E. coli, but should that prevent prescribing an effective short course of antibiotics? It wouldn’t make sense to lump this suspected E.coli stain in with the one that was isolated from the chronically catheterized 85 year old patient who’s on day ICU day 10. In the antibiogram, it is.

What’s most interesting to me as a pharmacist is that these reports represent an aggregate proportion of susceptibility data for a given isolate-antimicrobial combination.  Similar to the above example, consider a 20-something year old UTI.  If the E.coli is likely to be resistant to levofloxacin, the antibiogram cannot help predict what this antimicrobial will be appropriate. Sure the susceptibility to nitrofurantoin is 99%, but does that change when the isolate is resistant to levofloxacin? No idea.

Antibiograms may still have a place when tailoring therapy for nosocomial infections. Certainly, if other institutions provide more detailed information on antibiograms, follow the standardization of construction recommendations or antibiograms evolve with new technology, their use could help guide empiric antimicrobial therapy. But in the ED, the current limitations prevent the broad utilization of antibiograms.

Pakyz AL. The utility of hospital antibiograms as tools for guiding empiric therapy and tracking resistance. Insights from the society of infectious disease pharmacists. Pharmacotherapy 2007;27(9):1306-12 

Thursday, December 6, 2012

Cessation of the SOB: Glucagon for Asthma Exacerbation

Let us say you have a patient, SH, who presents to the emergency department with the following chief complaint:

"It's happening again- I just need to be intubated."

This seems to be more than a little interesting and you think to yourself, "What the heck? Let me check this out."

You then begin to recall that the patient looks a little familiar to you. In fact, SH has been to the ER more than a dozen times within the past three months. Her previous visits have all been related to asthma exacerbation secondary to ethanol abuse, and unfortunately, she has been non-compliant with her asthma medications. She has been intubated several times in the past and has required admission to the ICU.

She currently presents with tachypnea and acute shortness of breath. Physical exam reveals HR of 115 bpm, RR of 42 bpm with signs of accessory muscle use, and 88% oxygen saturation upon room air. SH also has decreased breath sound bilaterally with inspiratory and expiratory wheezing. In addition, readings from the peak flow meter are consistently in the red zone between 150 and 160 L/min.

Run of the mill treatment is started with oxygen therapy and nebulized solution of albuterol 2.5 mg and ipratropium 0.5 mg every 20 minutes times 3 doses. In addition, IV access is obtained, and a one-time dose of methylprednisolone 125 mg IV is ordered. SH does not show any improvement, and the decision is made to initiate a continuous solution of nebulized albuterol at a rate of 10 mg/hr.

Despite all these therapies, SH still shows no signs of improvement, and so "kitchen sink" therapy is started with a one-time dose of terbutaline 0.25 mg SQ and magnesium sulfate 2 g IV infusion. Even a loading dose of aminophylline 400 mg is ordered; after all, what harm can it do? With all these therapies being initiated, SH still is profoundly wheezing, and her oxygen saturation drops to 85% on room air. The ED attending physician looks to you and asks, "Can we try glucagon in this patient?"

You are stunned by this request. Theoretically, this makes sense. We know that glucagon is a 29-amino acid polypeptide hormone produced by the α-cells of the islets of Langerhans in the pancreas. It acts by stimulating adenyl cyclase to activate the synthesis of cyclic adenosine monophosphate (cAMP). So the next question you ask yourself is: are there any studies to support the use of glucagon in the management of asthma exacerbation?

A quick literature search on PubMed only reveals about a handful of studies related to this. One study demonstrated that approximately 60% of patients experienced a mean increase in peak expiratory flow rate by at least 60 L/min ten minutes after the administration of 1 mg of IV glucagon for patients with asthma exacerbation. However, in a randomized, double-blind, placebo-controlled trial simulated to evaluate the same study outcome, the administration of weight-based IV glucagon (0.03 mg/kg) showed no real benefit in improving bronchodilation in asthmatic patients who presented to the ED with bronchospasm. Interestingly enough, a study was conducted that evaluated the effect of nebulized glucagon in the management of bronchospasm in patients with a history of chronic stable asthma, which showed greater improvement in FEV1 compared to nebulized normal saline. Administration of glucagon through this route may be a reasonable option, especially in patients where IV access may be difficult to obtain.

Anecdotally, we have administered IV glucagon at a dose of 2 mg to select patients (including SH) at our institution for the management of bronchospasm associated with asthma exacerbation. Glucagon may be considered as a last-line option if patients with bronchospasm secondary to asthma do not show improvement with standard therapies.

Monday, December 3, 2012

Low vs Standard Dose Diltiazem

A few days ago I read a few tweets about evidence versus eminence-based medicine and the ensuing discussions.  I started to think of a number of examples of eminence based medicine I practice; but not out of old habits, or limited knowledge – but because there’s simply a lack of evidence.

Diltiazem dosing for AFIB rate control was one of them.  So sayeth the drug reference; the initial weight based diltiazem dose for rate control is 0.25mg/kg. If that didn’t control a patients rate, you could repeat a dose of 0.35mg/kg. Those large doses could drop a patient’s blood pressure, and a particular concern for patients with borderline blood pressure in the neighborhood of 90-100 systolic. Clinically, the dose could be empirically lowered in this case to say 0.15mg/kg to try to minimize the drop in SBP. But what’s the evidence?

Old data existed comparing standard dose diltiazem to various other rate control treatments: digoxin, amiodarone, metoprolol, etc. But until recently, evidence to suggest the effects of using a normal vs low dose diltiazem did not exist.

Now, I’m certain this article has been reviewed elsewhere, so I’ll try to summarize the meat of it briefly. The tagline of the study was low-dose diltiazem (0.14mg/kg ± 0.04) was as good as standard dose diltiazem (0.24mg/kg ± 0.02) and high dose (0.34 mg/kg ± 0.02) at achieving a positive therapeutic response (30 min post administration - reduction of the ventricular response rate to < 100 OR > 20% reduction from baseline).  Not surprisingly, there was a lower incidence of hypotension (but no clinically significant events as a result of the hypotension) in the low dose arm compared to standard and high dose.[1]

Although it wasn’t the most robust study, and no slam-dunk, it did finally provide some evidence to support using a lower dose in situations. More importantly, the ethos of this study was what I enjoyed the most – challenging what we think we know and putting our clinical habits to the test. Hopefully, this will inspire others to challenge their eminence-based practices. I know it has for me.

[1] J. Lee et al. Low-dose diltiazem in atrial fibrillation with rapid ventricular response. American Journal of Emergency Medicine (2011) 29, 849–854

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