Friday, May 30, 2014

My EpiPen expired! Can I still use it?

EpiPenThe above question is common from patients with a history of an allergic reaction seen for a repeat emergency department visit. The manufacturers of EpiPen caution not to use the pen beyond the expiration date, and if the drug solution becomes discolored (oxidation). But EpiPens are expensive! Is there harm in using the pen beyond the expiration date? What should we tell our patients?

Article Citation on Expired EpiPen

Simons FE, et al. Outdated EpiPen and EpiPen Jr autoinjectors: Past their prime? J Allergy Clin Immunol 2000; 105:1025-30. PMID 10808086

PICO Analysis

PICO Analysis
Finding
Population• Rabbits
Intervention• 34 EpiPens past their expiration date (1-90 months)
• Most were not discolored and did not contain precipitate
Comparison• Non-outdated EpiPens
Outcomes• Adult EpiPen epinephrine bioavailability in rabbits’ blood after IM injection
   - Maximum Blood Concentration in expired EpiPens 10.8 ± 0.9 ng/ml
   - Maximum Blood Concentration in non-expired EpiPens 26.2 ± 6.9 ng/ml
   - Obvious significant difference in bioavailability (p<0.05)

• Epinephrine content in outdated pens (%)
   - EpiPens (n=28): 51-102 vs. 105-111 in-date pens
   - EpiPen Jr (n=6): 55-93 vs. 86-114 in-date pens

Bottom Line

  1. Outdated Epipens start losing epinephrine once expired.
  2. A significant amount of epinephrine may still be present up to 90 months after the expiration date.
  3. We should always recommend in-date pens to be used and provide a new prescription or a refill if needed; however, as advocated by the publication article’s authors, if an expired, non-discolored EpiPen is the only out-of-hospital intervention available for an anaphylactic reaction, it should be used as the risk of harm is minimal with significant benefit.

Friday, May 23, 2014

Bookclub: How We Die

DNR/DNI, Code Blue, Cardiac Arrest, Traumatic Brain Injury, Exsanguination, Septic Shock, Respiratory Arrest…  and the list goes on. As healthcare providers, we are well versed in the medical and emergency resuscitations that can spiral into these dangerous arenas. Even if we don’t always know the exact cause, we know the mantra of ABCs and we stick to it until the end. The very last end… But the end of what? Where is the dignity in resuscitating a body that has already died? Ultimately the question becomes, are we as practitioners as well versed in letting go, in letting the body die, and then ultimately explaining that process to the family?

How We Die

This book originally was published in 1994 by Dr. Sherwin Nuland with the goal to “demythologize the process of dying”. He wrote this book to address a quandary that he had noticed between the death people stated that they wanted full of peace, love, and calmness and the death that they instead had which was clinical, chaotic, and sterile, also known as “modern dying” according to the author. Dr. Nuland also noticed that with the advent of hospitals and hospitalizations of the ill, people had become quite distanced not only from death, but also the process of dying. Whereupon prior generations lived with their grandparents until their passing, modern death happened in another location with actual physical separation. This only led to a lack of familiarity of the process of dying and, naturally a development of fear in this process.

Clinical Application

ALiEM Bookclub chose this book because of the daily reality of how much death affects our clinical practices not, especially in the emergency setting with patients that we know little to nothing about. Although this book is written for a non-medical person or someone with little to no medical training or understanding, we believed that the book has value for practitioners. This book can serve well as a foundation to develop palliative care skills. Chapters are broken up into diseases processes that explain the process of heart failure and the devastation of HIV. A particularly beautifully written chapter details the life and slow dying process the author’s own grandmother went through as she ultimately passed away at an elderly age.
Most of all, this book attempts to address head on, without shying away from any graphic details about the process of dying. This even went so far as to include the tragic story of a young girl who was murdered in front of her mother with Nuland detailing the exact process of how knife wounds can lead to vascular injury and ultimately to exsanguination. This role models for the readers how to approach these difficult discussions with patients and their patient families – using methods that are honest but frank, not afraid of the hard questions that patients may have.

Bookclub

Members of the book club convened and discussed the following questions. Please add your own questions, thoughts, and comments below.
  1. The author talks about realistically understanding goals of care, especially regarding terminal illnesses such as cancer, and potentially addressing these goals outside of medicine. What are your thoughts on this?
  2. How do you think the author felt about medical researchers and their general approach to medical problems?
  3. Would you suggest this book to medical students or nursing students? Would you suggest this book to a dying patient or to a family of a dying patient?
  4. What are challenges to providing effective palliative care in the ED setting?

Conclusion

Ultimately this is a great book for anyone interested in palliative care, ethics of dying, and challenges to modern healthcare. Most of all, this book is a reminder to stop during hectic ED shifts and consider those patients who may not be acutely at the brink of dying, but perhaps are suffering terribly from chronic illness. Consider having a personal conversation with them about their own thoughts of dying, concerns that they may have, medical or otherwise. The direction of the conversation may surprise you. Five minutes — we can all spare that much time to help someone regain their dignity and control over their own dying process.

Thursday, May 22, 2014

Article: Hypotonic maintenance IV fluids in pediatrics

IVbags2 copyA 6-month-old male presents to the emergency department with diarrhea and vomiting. Despite antiemetic therapy, the the child is unable to tolerate oral intake in the ED and so you opt to admit him to the hospital for IV fluids.  The pediatric hospitalist requests that you write maintenance fluids prior to admission to the floor. Utilizing the 4-2-1 rule you calculate maintenance needs and choose D5 ½NS as your fluid. This is what you had been taught to utilize in children. It seems appropriate… but is it?

Background

Holliday and Segar published their seminal work on the maintenance caloric and fluid needs of children in Pediatrics in 1957 [1]. As the paper utilized hypotonic solution to match presumed solute needs, subsequent generations of emergency physicians and pediatricians have relied upon hypotonic solutions to serve as the primary vehicle for which to deliver caloric and electrolyte needs. The original calculations recommended 0.2% saline however this has largely been supplanted by 0.45% saline with dextrose as a primary intravenous maintenance fluid. Though D5 0.45% saline is chemically hypertonic, in vivo it is an effective hypotonic solution due to the rapid uptake and metabolism of dextrose.
Recently there have been a few trials (reviewed in the systematic review we are discussing) that question the wisdom of using hypotonic solutions as maintenance fluid. It is theorized that hospitalized and critically ill children may have a non-osmotic stimulus for anti-diuretic hormone secretion potentially leading to hyponatremia and/or cerebral edema.   

Article Citation

Foster BA, Tom D, Hill V. Hypotonic versus Isotonic Fluids in Hospitalized Children: A Systematic Review and Meta-Analysis. J Pediatr. 2014 Feb 27.

Objective 

  • Systematic review of all studies comparing isotonic to hypotonic maintenance fluids in chilren assessing for hyponatremia

Study Methods 

  • Cochrane style systematic review in which a total of 10 studies met inclusion criteria and were included in the final analysis
  • 5 ICU studies, 4 ward studies, 1 mixed study
  • Patients had variety of illness (many were very sick) 
    • Large representation of PICU and post-operative patients 
  • Multiple different hypotonic fluids included across studies including 0.18%, 0.3%, and 0.45% saline
  • Primary outcome: hyponatremia (Na <135 mmol/L)
  • Secondary outcomes: 
    • Change in serum sodium from baseline
      • Moderate (<130 mml/L)
      • Severe (< 125 mmol/L)
    • Adverse events of hypernatremia (> 145 mmol/L)
    • Mortality

Results 

  • 11 RCTs included
  • Primary outcome
    • Relative risk for hyponatremia = 2.37 (1.72-3.26)
    • Assuming an estimated control event rate(CER) for hyponatremia of 5%, the Number Needed to Harm (NNH) = 15 (9-28)
    • Assuming an estimated CER for hyponatremia of 20%, the NNH = 4 (3-7)
      • The calculations of these NNHs are based upon the varying CER found in the various studies.
        • The control event rate describes how often an event in study occurs within the control group
        • To determine the NNH (as the NNT) we utilize the control event rate and the experimental event rate (EER—how often the event in study occurs in the treatment group).
          • NNH= 1/(EER-CER)
      • The authors utilized both the high and low end of the CER to give a range of NNH (4-15) with corresponding confidence intervals (3-28) depending upon the CER 
  • Secondary outcome
    • Change in serum sodium (5/11 studies described this statistic) = -2.46 (-3.11 to -1.81)
    • Mortality: none identified
    • Relative risk for hypernatremia (8/11 studies described this statistic) = 0.81 (0.32-2.04)
      • Reported about 0-6% incidence of hypernatremia using isotonic fluids
      • NNH not calculated due to nonsignificant findings 

Analysis

The studied population, that which the systematic review included, was heterogeneous and included disparate disease states lumping together floor patients admitted for various reasons with post-operative patients admitted to the PICU setting.  Though the underlying question of hyponatremia in the entire cohort may be equivalent (the I2 statistic did not demonstrate significant statistical heterogeneity) it may also be the case that sicker and post-operative patients have altered physiology from increased disease burden and represent the primary population in which ADH excess is triggered by non-osmotic stimuli (the actual at risk cohort).   
Due to the few studies included with routine pediatric EM admissions (e.g. dehydrated gastroenteritis) it is difficult to secondarily generalize these findings into the ED setting. It is also worth noting that there were no disease oriented outcomes delineated in either group from shifts in serum sodium concentrations. Though hyponatremia may predict subsequent neurological deterioration and cerebral edema, this systematic review did not find deleterious patient responses either because they do not occur or they are rare enough to not be found in the final analysis.

Future Directions

This article forces us to reassess conventional wisdom in the light of new experimental evidence. Hypotonic maintenance fluids were originally established using a now 60 year old study on the basis of presumed rather than clinically confirmed patient physiology. While this particular systematic review failed to find patient oriented harm associated with hypotonic maintenance fluids it did show an absolute alterations in serum sodium potentially predictive of poor patient outcomes.
The next step will be to verify the study results and make it more applicable to our ED patient population. A prospective study of pediatric ED patients admitted for disease entities requiring maintenance fluids could be undertaken comparing the two intravenous fluid tonicities, using laboratory and clinically relevant outcome measures. 

Wednesday, May 21, 2014

Cellulitis: Do Not Get Blood Cultures

BloodCultureBottle
You are treating a patient with left lower leg cellulitis. The nurse is going to establish IV access, draw blood work, and give analgesia and antibiotics. Before walking into the room, the nurse asks, “Do you need me to grab a set of blood cultures?” Additionally the hospitalist had asked you to order a “set of cultures” on your most recent cellulitis admission. Should you proceed?

Background

Cellulitis is one of the ten most common complaints in the ambulatory care setting which includes the emergency department (1-3). Patients are subclassifed into either complex or simple cellulitis depending upon their comorbidity.
  • Complicated cellulitis is defined as the presence of an immune-compromised status (HIV/AIDS, in active chemotherapy, status post organ transplantation), diabetes, or peripheral vascular insufficiency. Due to the extensive comorbidity, it typically requires treatment in the inpatient setting and blood cultures have been routinely recommended.
  • Uncomplicated (simple) cellulitis is most often treated with oral antibiotics that cover for Staphylococcus and Streptococcus species based on local antibiograms.

Utility of Blood Cultures in Uncomplicated Cellulitis

In 2005, Mills et al (4) performed a search of the best available evidence on blood cultures in patients with cellulitis. Five articles were identified:
Authors
Positive cultures
Contaminated cultures
Perl et al11/553 (2%)20/553 (3.6%)
Kulthanan et al20/150 (17.2%)
Lutomski et al4/25 (16%)4/25 (16%)
Ho et al1/130 (0.77%)0/130 (0%)
Hook et al2/13 (4%)No mention
The authors conclude:
“On the basis of the evidence available, blood cultures do not significantly alter treatment or aid in diagnosing the microbial organism in acute adult cellulitis in normal immunocompetent hosts. Therefore, it would be within the standard of care not to obtain blood cultures in immunocompetent patients who present with apparently uncomplicated cellulitis.”

Utility of Blood Cultures in Complicated Cellulitis

In a retrospective chart review by Paolo et al (5) in 2013, patients were classified by the authors as having complicated or uncomplicated cellulitis. All of the study participants had blood cultures drawn and a comparison was made between the two groups to determine the utility of cultures in this setting. The results were:
Cellulitis Type
Positive blood cultures
Contaminated blood cultures
Complicated29/314 (9%)13/314 (4%)
Uncomplicated17/325 (5%)10/325 (3%)
The authors stated, “A clinically significant change in management (a change in the class of antibiotic) was found in 6 of 314 cases vs. 4 of 325 controls (p =0.578; OR=1.5525; 95% CI 0.434–5.5541)… This group of clinically significant change in management was about 2% of the entire cohort and most would have been changed to a narrowed antibiotic. “
Patient #
Initial Antibiotic
Second Antibiotic
Blood Culture
Comorbidity
1KeflexZosyn, VancomycinCornebacteriumDiabetes
2NoneAugmentinStapylococcus saccharolyticusDiabetes
3VancomycinPenicillin GGroup B StrepDiabetes
4Zosyn, FlagylCephalexinStreptococcus salivariusChemotherapy
5ClindamycinOxacillinGroup B StrepChemotherapy
6KeflexLinezolidMRSAAsplenia
Additionally, out of their entire cohort, only 7 cultures were shown to have gram-negative bacteria. Due to the study time period (2005-2009), MRSA was not as prevalent in their community and is likely more common presently.

Conclusion

In both uncomplicated and complicated cellulitis, blood cultures have a low yield of becoming positive and when they are found to be non-contaminated, they are unlikely to significantly change management. The cases in which non-skin flora grow in the blood, the history from the patient usually has given the provider some cause to suspect bacteria other than routine skin flora.
 

References

Expert Peer Review

March 15, 2014
It is important to utilize diagnostic tests with the greatest likelihood of influencing the management of the presenting patient.  Each particular test that we use will demonstrate differential clinical utility based upon their underlying performance characteristics particularly in the form of sensitivity and specificity.  The combination of the intrinsic testing parameters develops the diagnostic threshold of the test; the point of clinical possibility in which the test should be appropriately applied.  An example is depicted below:
Pretest ProbabilityIn this scenario, we are looking at the changes in pre-test probability (to posterior probability) of a test given a presumptively high specificity and low sensitivity. As is known from basic EBM, specificity is the needed parameter to rule in disease whereas sensitivity rules out disease. This is evidenced by the steep slope of the maroon lines indicating a potentially relevant change in probability to discover disease whereas the green lines have a softer slope demonstrating the poor performance of the test to change what we initially thought given negative results. The combination of these attributes forms a diagnostic threshold (the horizontal dashed line)—the pre-test probability at which testing should or should not be performed. If we define a patient as likely to have disease (say 40% likely) and we are using a test with the parameters depicted above then our results are ultimately useless and we should not have tested in the first place. A positive and negative result still ends up as likely to have disease rendering the test moot.
Rates of positive blood cultures (pre-test probability) in cellulitis are estimated to be approximately 2% (1). In addition the rate of contamination (false positives) are either equal to or exceed the actual yield making the test a difficult one to recommend. In order for the test to be efficacious given a presumed 2% pre-test probability the testing parameters for clinical relevance would have to be astronomically good—unfortunately they are far from useful. A best estimate demonstrates a 4% sensitivity and an equally poor specificity making it difficult if not impossible to budge the 2% we started with prior to encountering the patient.
Our study (2) sought to determine if these same testing parameters held true in the complicated cellulitis group, a mostly unstudied and expertly defined subcomponent of all patients with cellulitis. As was to be expected the rates of contamination equaled the rates of positive yield for the entire retrospective cohort rendering the test as primarily useless. It is important to note however that two findings had high prediction of positive blood cultures—fever and diabetes. Fever is a parameter that may in fact not predict simple cellulitis but underlying bacteremia from the initial infection. Speculatively this may hold true not just for complicated cellulitis but may be true across all manifestations of disease—this study was not designed to answer this question. Given the retrospective nature of the study it can neither endorse nor exclude the discovered association between fever and positive cultures and therefore the totality of the clinical picture in these complicated patients should be taken into account prior to the ordering of cultures. The yield was also higher in diabetics rather than the rest of the cohort but as with the rest of this study this rarely resulted in a change of management. The argument has been made that bacteremia is a distinct disease from cellulitis that is clinically relevant though it may not result in change in antimicrobial coverage from empiric management. While this may be true it is not clear that the blood culture as opposed to the clinical parameters of the patient would matter in terms of the care for these individuals.

Bottom Line

Our study found little clinically relevant information gained by the addition of blood cultures to complicated cellulitis in a retrospective study. Further prospective studies should be undertaken to confirm these findings and determine if a subgroup of these patients (i.e. fever and diabetes) would benefit from cultures.

Tuesday, May 20, 2014

Beware of fluoroquinolones: You, your patient, and the FDA

Levofloxacin
Fluoroquinolones are a widely used class of antibiotic that are effective in treating a wide variety of infections. Despite their popularity there is increasing concern regarding to the potential complications associated with these agents. In 2008, the U.S. Food and Drug Administration (FDA) issued a black box warning involving fluoroquinolone use and an increased risk of tendon rupture. More recently in 2013 the FDA released another warning regarding the risk of peripheral neuropathy and required additional warnings to be added to the drug labels [1].

Tendinopathy: How it became a black-box warning

Starting in the early 1980s, case reports began to emerge that attempted to connect fluoroquinolone use to the increased risk of Achilles tendinopathy [2]. In 2003, a WHO survey performed in Australia reported an increase in tendon rupture in patients taking fluoroquinolones and found ciprofloxacin to be the culprit in ~90% of cases [3-4]. Since then similar reports of tendon rupture have emerged involving a wide range of fluoroquinolones [5]. In 2008, the FDA issued a black-box warning for all fluoroquinolone products that indicated an increased risk of tendon rupture in patients taking these agents [6].

Peripheral Neuropathy: How it became a warning

Fluoroquinolones have carried a warning regarding the risk of peripheral neuropathy since 2004. In 2013, after reviewing several years of reports from the Adverse Events Reporting System, this warning was enhanced. While the exact incidence of these events is somewhat unclear, often peripheral neuropathy developed after only a few days of treatment and at times could continue chronically [1].

What exactly is the risk for the patient?

When compared to the general population, patients taking fluoroquinolones have a 4.1 fold increased rate of Achilles tendon rupture. This risk is increased in:
  • Men
  • Age > 60 years
  • Chronic renal disease
  • Taking corticosteroids - there is a 46 fold increase in the rate of tendon rupture when compared to age-matched controls [7] 
  • Recipients of solid organ transplants
Typically symptoms of tendinopathy will start about 6 days after the onset of treatment, yet the risk of tendon rupture remains elevated for up to 90 days, with over 50% of patients experiencing symptoms that began after their treatment was completed [8].
The risk factors associated with fluoroquinolone use and peripheral neuropathy are still somewhat unclear. Providers are advised to monitor all patients for any signs of nerve damage including pain, numbness, weakness, or changes in sensitivity to pain or temperature [1].

What is the risk to the provider?

Lawsuits related to complications from fluoroquinolones are increasing. In recent years, levofloxacin has come under particular scrutiny as its popularity has increased. In 2010 a jury awarded $1.8 million to an 82 year old man who experienced bilateral calcaneal tendon ruptures after taking levofloxacin. As of 2011 there were over 2,500 lawsuits pending with regards to tendon rupture in the setting of fluoroquinolone use [9]. As FDA warnings in regards to neuropathy are published, there will likely be a rise in related lawsuits.

So should we stop prescribing fluoroquinolones?

Fluoroquinolones remain an effective antibiotic that can be used to treat a wide variety of conditions. In patients with community acquired pneumonia, there is growing resistance to macrolide therapy and several guidelines now recommend respiratory fluoroquinolones as the first line agent of choice [10]. Additionally, fluoroquinolones are suitable for patients who are allergic to penicillin, and are also available in once daily dosing [11]. While the risk of complication from these antibiotics cannot be ignored, they are arguably the drug of choice to treat a variety of infections.

How to limit your risk

Provider risk is increased any time medications are used that carry significant FDA warnings. Despite this risk, in certain clinical situations, the relatively minor risk of tendinopathy is vastly outweighed by the benefit offered by this class of antibiotics. The FDA warning advises providers to avoid using fluoroquinolones in patients who have a high risk of tendon rupture. When prescribing these medications, providers should have a discussion with the patient involving the associated potential risks and benefits. In addition providers should advise patients to limit high impact physical activity and should discuss signs and symptoms of tendon injury that should prompt an immediate return to the ED. If a patient presents with any signs of tendon injury after taking fluoroquinoloes, the medication should be stopped immediately and an alternative class of antibiotics should be used.
Documenting a clear discussion of potential risk and benefits of using fluoroquinolones is a crucial step to minimize risk in the event of a bad outcome. Given the fairly substantial FDA warnings associated with this class of drug, some emergency departments have developed standardized warnings to place in the chart anytime a patient is prescribed a fluoroquinolone.
I am prescribing a fluoroquinolone for the patient to treat their pneumonia. I have discussed the risks associated with this medication including risk of tendon rupture and neuropathy. I have considered other classes of antibiotics and I think this is the most appropriate choice of medication.The patient has verbalized an understanding of these risks, has been advised to limit strenuous exercised while taking these medications, and will return immediately for any pain, swelling or if they develop any new or concerning symptoms.  With the increasing number of cases being filed in response to fluoroquinolone-associated complications, providers should be aware of the significant medicolegal risk that can accompany the use of these medications. While fluoroquinolones remain an effective and reasonable choice of antibiotics, when using these medications providers should discuss and clearly document potential risks and benefits with all patients.
This post belong’s to Dr. Matthew DeLaney’s series on Everyday Risk in Emergency Medicine (EREM).

Monday, May 19, 2014

New Antibiotic Dalbavancin: Should we use this in the ED?

antibiotic iv new antibiotic will soon be approved for skin and soft tissue infections (SSTIs): dalbavancin. The company behind the drug will likely begin marketing heavily to emergency physicians as many patients with SSTIs seek care in the Emergency Department (ED). However, should we seriously consider dalbavancin as an addition to an ED’s arsenal against SSTIs and should it change our practice?
Since we are talking about a new medication, my disclaimer: I have no conflicts of interest to disclose.

Dalbavancin: About the Drug

  • Bacterial coverage: Think of it as vancomycin – great at covering gram + bacteria (including MRSA)
  • Dosing: Two-dose regimen given once weekly as a 30 minute infusion
  • Adverse events: Similar to any antibiotic (nausea, vomiting, diarrhea, rash)

Evidence Thus Far*

Two  phase III trials were just completed (DISCOVER 1 and DISCOVER 2), where DISCOVER stands for “Dalbavancin for Infections of the Skin COmpared to Vancomycin at an Early Response.”
These non-inferiority trials have not been published in a peer reviewed journal at the time of writing this, but the data has been submitted to the FDA for approval.
PopulationMostly white patients (~90%) needing at least 3 days of IV antibiotic therapy for SSTI (locations: North America, Europe, South Africa, Asia)
InterventionRandomized double-blind once weekly dalbavancin x 2 weeks
ComparisonIV vancomycin for at least 3 days with an option to switch to linezolid PO to complete 10-14 days of therapy
Outcome (primary)Halt of lesion spread and resolution of fever at 72 hours
ConclusionsDalbavancin is non-inferior to IV vancomycin +/- linezolid

Should we use dalbavancin in the ED?

The patients in DISCOVER 1 and 2 trials were all deemed to need 3 days of intravenous antibiotics. From an ED perspective, these patients are sick enough to be admitted. It is unlikely that emergency physicians will discharge a potentially septic patient with an obvious skin source regardless of the antibiotic’s week-long pharmacokinetics. We might be tempted to treat less sick SSTIs with dalbavancin – even those we would treat with POs and discharge home. However, in a patient with a stable SSTI we really shouldn’t be using ANY IV  antibiotics , as I posted on ALiEM earlier.
Once weekly dosing of dalbavancin is attractive and could potentially eliminate some compliance issues with 10-14 days of BID-QID oral antibiotic therapy that we currently use. However, dalbavancin will require a second ED visit for a second infusion. It could be argued that patients with very poor compliance are just as unlikely to return to the ED for a follow up second infusion-visit as they are to take their oral antibiotics, especially if they defervesced and are feeling much better after three days.
One of the biggest factors, especially for county hospitals taking care of underserved or uninsured patients, is the cost. Pricing is still a secret; however, my colleagues and I have been quoted different prices, ranging from $1,000-2,500 per infusion, not accounting for costs of two ED visits and other non-medication related charges. The DISCOVER 1 and 2 trials have only shown that dalbavancin is non-inferior to standard care for admitted SSTIs: much less expensive IV vancomycin followed by an oral antibiotic. Although linezolid was the subsequent oral antibiotic studied in these trials, there is no reason why using bug susceptibilities to choose another inexpensive oral antibiotic (like trimethoprim/sulfamethoxazole) would be inferior.
There may be a place for dalbavancin in the treatment of gram positive infections, but just not in the ED. Although no data exists yet on osteomyelitis, dalbavancin could theoretically spare patients from central line placements and prolonged home antibiotic infusions.

Final Thoughts

Antibiotics are not high-profit medications. Any company who invests resources to study a new antibiotic in the age of multi-drug-resistant bugs should be commended. That being said: Dalbavancin is not an antibiotic that should be first or second line treatment for SSTIs in the ED. Even if the company adjusts the price to <$100 per dose, hospital antimicrobial stewardship programs need to rationalize and limit the use of this new antibiotic for cases when cheaper non-inferior treatments have failed. Advertisers’ persuasion of better compliance for “high-risk patients,” convenience, and non-inferiority, are not enough to challenge the standard care of SSTIs in the ED.
Would love to hear your thoughts.

Saturday, May 17, 2014

Clinician Educator: The agent for change in medical education

Socrates_and_PlatoSome people consider teaching and learning much more difficult than rocket science [1]. Teaching and learning is such a complex process that researchers are still having debates in different areas including: how it works, how to assess it, and how to research it. For the most part it is safe to presume that different people have different learning philosophies and this is, most likely, how they teach [2]. Because we are a product of our past and form strong habits, these might inadvertently impede the search of more effective and efficient educational activities. Research in education, just like research medical practice, may challenge our most held beliefs and bring to light better educational practices.

Does educational research make a difference?

Conducting and implementing educational research findings in and outside of the learning environments is quite challenging. Learning is very complex with numerous variables and confounding factors. Although we can theorize and hypothesize how learning occurs we don’t have direct evidence of this complex process. We can only predict that learning might occur under certain situations or infer it has occurred via evidence from certain assessments. The reliability and validity of assessments as evidence of learning is another complex topic widely covered in education and beyond the scope of this post. Most people, formally trained in education or not, might base their teaching and assessment practices on how they were taught or common beliefs. However, sometimes these practices may be outdated, misunderstood, and even erroneous [3].
Educational research plays an important role in improving practice, dispelling misbeliefs, and debate different points of views. For instance, in a manuscript by Kirschner et al advocate why direct instruction works as an approach to learning, while stating that minimally-guided instruction does not [4]. In reply Schmidt et al. defended minimally-guided problem based learning as an effective instructional method [5]. In contrast, Billett has done extensive work on community of practice and how apprenticeship leads to construction of knowledge in a situated learning environment [6]. These studies and opinions demonstrate the existence of different points of views and evidence when it comes to teaching and learning.

One size does not fit all

One of the principles of competency medical based education (CBME) is recognizing that education is not one-size-fits-all. It is recognized that students learn differently and at different rates. The model of CBME is based on individualized learning and differentiation of students’ learning. As stated by Gruppen et al [7]:
“Competency-based education promotes a necessary flexibility in the time and sequence of what is to be learned that is regulated by the needs of the learner. Therefore, CBE allows for a highly individualized learning process rather than the traditional, lock-step, one-size-fits-all curriculum.”
This suggests that educators should be more skilled in fostering a professional practice that benefits every learner in his/her own development. Individualized learning should be supplemented with differentiated teaching practice to foster long-term, self-regulated learning habits. In addition, new emerging pedagogical practices and learning environments might pose a great challenge in if learning conditions are not optimized.

Pedagogical practices in how we teach are not standardized

McLeod et al found a discrepancy in opinion between clinical teachers and educator experts on the importance of which pedagogical practices should have priority in medical education [8]. Differences in practice have been categorized into several factors such as location and years of practice, indicating that clinical teaching is not standardized [9]. Unfortunately, even at the professional level, practitioners do not see eye to eye when it comes to pedagogical practices. Wide variations exist, maybe even at the local level.
That being said, the basics in pedagogical knowledge may be taught [10]. Teachers can learn pedagogical practices and integrate it in their daily teaching routines. For instance, teachers can practice in an informed way if they practice in a scholarly manner [11]:
  • Implement evidence-based teaching practices
  • Make observations and reflect on their practices
  • Discuss their practice with others and obtain peer evaluations

Scholarship of Teaching and Learning

Scholarly educational practices are important, because it dispels bias, myths, misconceptions, or not optimized practices. Furthermore, the scolarship of teaching and learning (So TL) takes scholarly teaching to a higher level where the practitioner conducts research while educating and publishes the results adding to the existing body of knowledge and for others’ consideration. In this video, education experts explain what scholarship of teaching and learning means to them and the key characteristics of its practice:

The Clinician Educator

Although the practice of SoTL has been around for some time, its recognition and implementation have not been as successful as other practices delineated in Boyer’s scholarship framework. Sherbino et al identified key roles and competencies of the Clinician Educator which expand beyond bedside teaching [12]. These role and competencies may be able to help implement the principles behind the SoTL and disseminate its practice. The table below is extracted from the study and identifies important competencies of the Clinician Educator which support important aspects of teaching and learning.
Clinical Educator Competencies

Conclusion

We all have beliefs, evidenced or not, about how we learn, we are also under the influence of tradition (“we have always done it this way”). Tradition and tradition of “new” discourse might be reasons why some might find it difficult to “get off the carousel” [13]. It is very easy to think of teaching and learning as just “transferring” knowledge from a textbook or from one person to another, but we have come to understand that the process is much more complex than a simple word or theory can describe [5]. Educational research, scholarly teaching, and the scholarship of teaching and learning can bring a better informed, effective, and efficient practice to the world of medical education. We also have to keep in mind that not everything discovered in research is practical, which again brings into play the importance of context and professional judgement. The Clinician Educator can be the agent who connects the whole in medical education.

Neuraminidase Inhibitors for Influenza – The Truth, The Whole Truth, and Nothing But the Truth Finally

Influenza
ver the last 5 years, the use of neuraminidase inhibitors for the treatment of influenza has skyrocketed. Emergency physicians have been pushed to prescribe these medications under the belief that they reduced symptoms, the risk of complications, hospitalizations, and transmission. However, the recommendation for the use of these drugs has never sat on firm evidence-based ground. So what did we know then, and what do we know now?

Background

A prior Cochrane review published in 2012 noted that much of the data was unavailable for them to review as it was not released by Roche pharmaceuticals [1]. The available data only supported a reduction in symptoms but marketing focused on reduction in complications and transmission. Many physicians have remained skeptical of the utility of these drugs. Why? Well, what we’ve always known is that the complete set of data and studies was never released.

What’s New?

Last week the BMJ published two systematic reviews on these drugs (via the Cochrane Acute Respiratory Infections Group) along with a number of editorials on the topic. With full access to the data, the blinders are off. We have a full picture of the data, and it doesn’t look good… at least not for oseltamivir (Tamiflu) and zanamivir (Relenza). Let’s take a look at each systematic review.

Article #1: Oseltamivir (Tamiflu)

Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ. BMJ 2014; 348: g2545. [2]
Design: Systematic review of RCTs on adults and children
Main outcome measure: Time to alleviation of symptoms, complications, hospital admissions and adverse events
Outcome measure
Finding
Alleviation of symptomsShortened by 16.8 hours with oseltamivir
Admission to hospitalNo difference
Reduction in confirmed pneumoniaNo difference
Other complicationsNo difference
Transmission in prophylaxis groupNo reduction
Side Effect
Results
NauseaIncreased (NNH 28)
VomitingIncreased (NNH 22)
Psychiatric eventsIncreased (NNH 94)
HeadacheIncreased (NNH 32)
* NNH = Number needed to harm 
Summary: Oseltamivir led to a minor decrease in time to symptom alleviation with no benefit for complications, hospitalization or transmission. Side effects were common.

Article #2: Zanamivir (Relenza)

Heneghan CJ, Onakpoya I, Thopson M, Spencer EA, Jones M, Jefferson T. [3]
Design: Systematic review of RCTs on adults and children
Main outcome measure: Time to alleviation of symptoms, complications, hospital admissions and adverse events
Outcome Measure
Finding
Alleviation of symptomsShortened by 14.4 hours with zanamivir
Admission to hospitalNo data
Reduction in confirmed pneumoniaNo difference
Other complicationsNo difference
Prophylaxis1.98% reduction in symptomatic influenza (NNT 51)
  Summary: Zanamivir led to a minor decrease in time to symptom alleviation with no benefit for complications or hospitalizations. There was a small decreased in transmission. Zanamivir was well tolerated without any major side effects seen in this data set.

Conclusions from these articles

Oseltamivir and zanamivir treatment showed modest decreases in time to symptom alleviation in comparison to placebo. However, there was no comparison made to standard supportive therapy for reduction of symptoms. A little acetaminophen or NSAID may be just as effective. Additionally, neither medication reduced the risk of complications or any other clinically important outcomes. Oseltamivir frequently led to side effects that may be worse than influenza itself. Lastly, prophylaxis was ineffective with oseltamivir and showed only modest benefits with zanamivir.

Editorial

In addition to the two Cochrane Acute Respiratory Infections Group publications, the BMJ published an accompanying. The authors discuss a number of issues but focus on the fact that despite this drug being approved for use for the last 15 years, we’ve never had access to the full data set. Roche pharmaceuticals left scores of data unpublished and, more insidiously, selectively published the studies that supported the use of the drug. The result is that billions have been spent on these drugs for treatment of influenza, prevention in close contacts of patients with influenza, and in creating stockpiles of medications in the event of an epidemic or pandemic. These issues have been picked up in the mainstream media  as well.
We, as clinicians should demand more transparency. It would seem reasonable for regulatory organizations to require the disclosure of all data, not just published data, before approving a drug.

Friday, May 16, 2014

PEITHO Trial: Fibrinolysis for Intermediate-Risk Pulmonary Embolism

What-is-a-Pulmonary-Embolism
Most of us would agree that massive PE is treated with fibrinolysis and non-massive PE is treated with anticoagulation. The area of great debate has been the optimal treatment for sub-massive PE. The MOPETT Trial was published in January 2013 and although the patient population was small, it did show a huge benefit in pulmonary pressures at 28 months with fibrinolysis. The next study we have all been waiting for is the Pulmonary Embolism Thrombolysis (PEITHO) trial, which was just published yesterday in the NEJM, evaluating fibrinolysis for patients with intermediate-risk PE.

Background

Half of the cases of pulmonary embolism (PE) in the United States are diagnosed in the Emergency Department and follow ACS as the second most common cause of sudden unexpected death in outpatients. PE is typically broken down into three major categories:
  • Massive PE: Hemodynamic compromise with a systolic blood pressure of <90 mmHg
  • Sub-Massive PE: No hypotension but right ventricular strain or myocardial necrosis
  • Non-Massive PE: No hemodynamic compromise and no RV strain

Article Citation

Meyer G, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. New Engl J Med. 2014 Apr 10.

Article Overview

The purpose of this study was to determine the clinical efficacy and safety of fibrinolytic therapy with a single-bolus injection of tenecteplase, in addition to standard anticoagulation therapy in normotensive patients with an intermediate-risk PE.
Intermediate-risk PE was defined as acute RV dysfunction and myocardial injury without overt hemodynamic compromise.
What they did:
  • Randomized, double-blind, placebo-controlled trial of 1,005 patients with “intermediate-risk” PE
  • 76 sites in 13 countries
  • Tenecteplase plus heparin vs placebo plus heparin
  • Patients were eligible if they had ALL of the following:
    • Age ≥ 18 years
    • Confirmed PE with onset within 15 days
    • RV dysfunction (diagnosed on echocardiography and/or CT)
    • Myocardial injury (diagnosed with positive cardiac troponin I or T)
Treatment regimens:
  • Treatment arm: Weight-based tenecteplase (range: 30 – 50 mg) given as an IV bolus + standard anticoagulation
  • Control arm: Placebo + standard anticoagulation
Primary outcomes:
  • Death or hemodynamic decompensation within 7 days after randomization
Safety outcomes:
  • Extracranial major bleeding within 7 days after randomization
  • Ischemic or hemorrhagic stroke within 7 days 
  • Serious adverse events within 30 days
Results:
Outcome
Tenecteplase Group
Placebo Group
P Value
Death at 7 days1.2%1.8%0.42
Hemodynamic compromise at 7 days1.6%5.0%0.002
Extracranial bleeding at 7 days6.3%1.2%<0.001
Stroke at 7 days2.4%0.2%0.003
Death at 30 days2.4%3.2%0.42
Limitations:
  • There is no mention of pulmonary pressures in the results 
Conclusion:
In normotensive patients with intermediate-risk PE, death and hemodynamic decompensation are reduced with treatment of tenecteplase, but there is also a significant associated risk for intracranial and other major bleeding.

My thoughts

  • Fewer patients in the tenecteplase group developed persistent hypotension (1.5% vs 3.6%), required catecholamines (0.59% vs 2.8%), mechanical ventilation (1.6% vs 3.0%), or cardiopulmonary resuscitation (0.19% vs 1.0%).
  • The paper states that the risk of bleeding in younger patients is lower compared to older patients; however, patient subgroup analysis used an arbitrary pre-specified age (≤ 75 years vs > 75 years) showing a slightly greater risk for major extracranial bleeding in older patients. This risk, however, was not statistically significant (p=0.09).
  • Although the risk of EXTRAcranial bleeding was lower in the ≤ 75 years group, there was no mention of decreased INTRAcranial hemorrhage in this group as well. So it is unclear if there was a difference in overall bleeding complications between the age groups.
  • Would have liked to see a “safe dose” or “reduced dose” strategy studied here.

Clinical Bottom Line

Per these PEITHO results, there was a significant increase in hemorrhagic complications with full dose tenecteplase in intermediate-risk PEs. The treatment, however, was also associated with a slight clinical benefit.
We concur with the accompanying NEJM editorial [1]. In brief, the results suggest that acute PE patients WITHOUT overt hemodynamic compromise should be carefully monitored and receive standard anticoagulation only (despite demonstrating RV dysfunction and myocardial injury) given the low mortality rate of 1.8% in the placebo group. Rescue thrombolytics can be considered once patients demonstrate hemodynamic instability. The risk of GIVING thrombolytics may be lower than NOT GIVING thrombolytics at this point.

Thursday, May 15, 2014

Understanding Phenytoin Equivalents

fosphenytoin image 1 (1)Sometimes, in an effort to make things simpler, we actually make them more confusing. Such is the case with phenytoin equivalents. 
Fosphenytoin is a water-soluble prodrug of phenytoin. After IV administration, much of the fosphenytoin is metabolized to phenytoin within 15 minutes. Advantages over phenytoin include the option for IM administration and less cardiotoxicity allowing for faster infusion rates. Even the potential for hyperphosphatemia from the release of phosphate is generally inconsequential.

So, where is the confusion? 

If you want the patient to receive 500 mg of phenytoin, then you simply order fosphenytoin 500 mg PE (where PE stands for phenytoin sodium equivalents).
But… if you turn the vial around and look at the side, you’ll notice it says that each 10 mL vial contains fosphenytoin sodium 750 mg. Wait, so do we need to order fosphenytoin 750 mg to make sure the patient receives phenytoin 500 mg?
fosphenytoin image 2 (1)

Phenytoin Equivalent: Keeping it simple

Most, if not all, institutions have the process set up so that fosphenytoin is ordered as phenytoin equivalents. So, keep it simple.
  1. Choose your favorite phenytoin dosing calculator
  2. Calculate a dose
  3. Order that amount of fosphenytoin in PE units
I would have preferred to just learn a new weight-based dose for fosphenytoin, completely separate from phenytoin. But, this is what we have. Don’t over-think it. That’s where the confusion sets in.

Trick of the Trade: Making your own homemade ultrasound gel

You are spending a month in rural Kenya, doing an ultrasound teaching course. Your enthusiastic participants have been ultrasounding every chance they get. Unfortunately, this has caused your ultrasound gel supplies to dwindle. It will be a month before a new shipment of gel arrives from Nairobi. This gel will cost about $5 per bottle, which is a considerable expense for the local hospital’s budget.

Trick of the Trade: Homemade ultrasound gel

With a few simple and ubiquitous ingredients, you can make your own ultrasound gel to use.

PIC1

Equipment Needed 

  • Corn starch
  • Water
  • Pot or pan
  • Heat source
  • Empty and clean bottle 

PIC2

Technique

  1. Combine 1 part corn starch to 10 parts water in a pan. Here, we use ¼ cup corn starch to 2 ½ cups water to make about 2 gel bottles full.
  2. Heat this mixture while stirring constantly at medium heat for 5-10 minutes.
  3. When the substance begins to boil, turn off the heat and allow the mixture to cool.
  4. Pour the mixture into a clean, preferably sterilized, container. Here, we use an old commercial ultrasound gel bottle which we placed in boiling water for 10 minutes first.
  5. Ultrasound away! Note that the gel should be used within 48-72 hours for best results. After that, it may begin to separate a bit.
PIC3

Word of Caution

This homemade gel does not have the same bacteriostatic ingredients that are in commercial ultrasound gel. Therefore we do no recommend its use for skin and soft tissue infections.

Tuesday, May 13, 2014

What makes a good clinical educator?

appleIn this constantly evolving world of learner competencies, assessments, and milestones often is forgotten the important role of clinical teachers. We can all remember clinical instructors that stand out despite the grueling years of medical school and residency training. We admired them for various reasons and remember the insights and teaching pearls they bestowed upon us. But what exactly were the qualities that they possessed that other instructors did not have? What exactly did they have that made them a good clinical teacher in medicine?

Good Clinical Educator

The authors of the 2008 Academic Medicine paper “What makes a good clinical teacher?” wanted to know exactly that [1]. And so they did a qualitative analysis of 68 articles, essays, and public addresses published from 1909-2006 . Surprisingly, they found that those qualities listed more often were noncognitive skills although cognitive skills were definitely highly considered.
Noncognitive skills were defined as relationship skills, emotional states, and personality types. Examples of this included those instructors who were inspiring and motivating – encouraging learners to be the best that they could be. Cognitive skills were defined as those involving perception, memory, judgment, reasoning, and procedural skills. An example would be good medical decision making for patients with chest pain.
The most common themes the authors found to be present in good clinical teachers in medicine included:
  1. Medical / clinical knowledge
  2. Clinical and technical skills / competence, clinical reasoning
  3. Positive relationships with students and supportive learning environment
  4. Communication skills
  5. Enthusiasm
The authors best summarized their findings as
“excellent teaching, although multifactorial, transcends ordinary teaching and is characterized by inspiring, supporting, actively involving, and communicating with students”.
The authors conclude there must be a recognition of the importance of noncognitive skills in those who want to improve as clinical educators. Although the medical knowledge is important, that is merely the standard by which all educators must have. But to excel requires inspiring and motivating.
What are your thoughts regarding this paper? Think back to those educators that you had that made a lasting impact? What was it about them that made them so special? Do you agree with this list of attributes above? Or do you have anything that you would add or detract?
“I’ve learned that people will forget what you said, people will forget what you did, but people will never forget how you made them feel.”
- Maya Angelou

Expert Peer Review


Outstanding clinical instruction is vital to a learner’s growth and development. Many qualities of outstanding instructors, identified in Sutkin’s article [1] and elsewhere [2-4], help educators in or outside the emergency department be successful. Didactic sessions and lectures in a conference room or auditorium, simulation, journal club, or podcasts are better with great instructors. Bedside teaching offers one venue for emergency physician educators. Despite knowing that good clinicians aren’t always great instructors, Niki labeled Sutkin’s as “Good clinician”
Where teaching takes place, its purpose and the audience matter. Formal teaching rounds by internal medicine faculty in a conference room to a team of learners at various levels without interruption rarely matches the style of, and opportunities for, teaching in the ED. Mandatory morning lectures to tired, hungry, distracted, or disinterested residents provide teaching opportunities without interruption, but infrequently deliver content in a manner that fosters integration and retention [5-10].
Bedside teaching is not without problems too. One example occurs when a learner presents a patient and the instructor focuses on the neurologic examination rather than the organ system responsible for the patient’s condition. The instructor may be an expert in neurology, therefore preferring to direct all learning towards his strength. This affords him comfort, and allows him to demonstrate his expertise. If you were to ask the instructor whether or not his teaching was effective, his answer would be an emphatic “yes.” Sadly, however, what the learner needed was teaching about the GI and cardiac systems responsible for the patient’s symptoms. The learner likely didn’t appreciate the instructor’s neurology expertise at that moment. Consequently, the learner considers the teaching to be poor.
As instructors, we must pay attention to our lesson, its appropriateness for the situation, and to the learner (and therefore, the patient). Furthermore, learners are better able to apply material that is relevant to their current educational demands, and are therefore more likely to retain this knowledge over time. Focused teaching creates a better “result” from their perspective.
Outstanding instruction requires practice. It requires a strong (not encyclopedic) fund of knowledge. Often individuals who know “everything” about a topic are not good teachers because they fail to translate their knowledge in a manner that allows learners to integrate new facts, skills, and reasoning abilities into something they not only can recall, but also apply. These shape the competencies, proficiencies, and milestones getting so much attention.
The key is to approach teaching in ways that acknowledge both the learner and the context. Most agree that poor teaching is better than no teaching. Yet outstanding instruction requires passion, commitment, integrity, and strong noncognitive skills. It should go without saying that making stuff up is never a good idea, may be dangerous, and can result in a teacher losing credibility rather than impressing learners.
Good listening skills are important to good clinical teaching because they allow an instructor to discover what learners desire to learn, how they think, and how much they truly understand. As instructors, we can engage learners by asking questions, soliciting input, and identifying whether or not they understand our message. It always helps me to remember that the success of learners equates to successful instruction.
Good teachers remember to teach to learners, not at them. They make their content interesting and teach with enthusiasm. They don’t focus only on their own strengths, but also on their learners’ needs. Our patients provide plenty of wonderful material for teaching. All patients have a story. These stories (some more interesting than others) offer instructors “teachable moments.”
Many terrific resources exist about clinical teaching [11-19].Here are a few pearls:

  • Adapt teaching to your audience, the environment, and the context
  • Teach to (or with) your learners, not at them
  • Be patient
  • Have a plan
  • Listen well and ask questions to engage your learners
  • Be as prepared as possible whenever possible
  • Limit the number of key messages
  • Admit what you don’t know and be comfortable looking things up
  • Demonstrate sensitivity to, and respect for, your learners and their time
  • Take advantage of a teachable moment
These pearls should help teachers be better. You know what? These qualities are similar to the qualities that make a good clinician. Maybe Niki was right.

Gus Garmel, MD FACEP FAAEM, Clinical Professor (Affiliate) of Surgery (EM), Stanford University School of Medicine, Former Co-Director, Stanford/Kaiser EM Residency Program, Senior EM Faculty, TPMG, Kaiser Santa Clara, CA, Consultant to Regional GME, Kaiser Northern CA, Oakland, CA, Senior Editor, The Permanente Journal, Portland, OR

References

  1. Sutkin G, Wagner E, Harris I, Schiffer R. What Makes a Good Clinical Teacher in Medicine? A Review of the Literature. Acad Med 2008;83:452-66.
  2. Wright SM, Kern DE, Kolodner K, et al. Attributes of Excellent Attending-Physician Role Models. New Engl J Med 1998;339:1986-93.
  3. Avegno J, DeBlieux PMC. Characteristics of Great Teachers. In Practical Teaching in Emergency Medicine. Rogers RL (ed). Wiley-Blackwell. UK. 2013:285-94.
  4. Bandiera G, Lee S, Tiberius R. Creating Effective Learning in Today’s Emergency Departments: How Accomplished Teachers Get it Done. Ann Emerg Med 2005;45:253-61.
  5. Kerr C. Death by Powerpoint: How to Avoid Killing your Presentation and Sucking the Life out of your Audience. ExecuProv Press. Santa Ana, CA. 2001.
  6. Skeff KM, Stratos GA, Mygdal W, et al. Faculty Development: A Resource for Clinical Teachers. J Gen Intern Med 1997; 12(Suppl 2):S56-S63.
  7. Skeff KM, Stratos GA. Methods for Teaching Medicine. ACP Press. Philadelphia, PA. 2010.
  8. Shulman LS, Hutchings P. The Wisdom of Practice: Essays on Teaching, Learning, and Learning to Teach. Wilson SM (ed). Jossey-Bass. San Francisco, CA. 2004.
  9. Ende J. Theory and Practice of Teaching Medicine. ACP Press. Philadelphia, PA. 2010.
  10. Guth TA. Resident as Educator: A Guidebook Written by Residents for Residents. EMRA. Irving, TX. 2013.
  11. Cooke M, Irby DM, O’Brien BC. Educating Physicians: A Call for Reform in Medical School and Residency. Jossey-Bass, San Francisco, CA. 2010.
  12. Kelly SP, Shapiro H, Woodruff M, et al. The Effects of Clinical Workload on Teaching in the Emergency Department. Acad Emerg Med 2007;14:526-31.
  13. Thurgur L, Bandiera G, Lee S, Tiberius R. What do Emergency Medicine Learners Want from their Teachers? A Multicenter Focus Group Analysis. Acad Emerg Med 2005;12:856-61.
  14. Whitman N, Schwenk TL. The Physician as Teacher, 2nd ed. Whitman Associates. 2007.

MEdIC Series: Case of the Unexpected Outcome

CryEmergency medicine is a specialty that requires a level of comfort with uncertainty. No matter how good of a clinician you are, at the end of the day there will be patients that, despite solid medical care, will have an unexpected outcome. In addition to being potentially emotionally devastating, a serious miss can make us question our competence and shift our practice patterns from evidence- to anecdote-based. Dealing with these issues productively will be the topic of discussion in this months MEdIC.

MEdIC Series: The Concept

Inspired by theand led by Dr. Teresa Chan and Dr. Brent Thoma , the Medical Education In Cases (MEdIC) series puts difficult medical education cases under a microscope. On the fourth Friday of the month, we pose a challenging hypothetical dilemma, moderate a discussion on potential approaches, and recruit medical education experts to provide “Gold Standard” responses. Cases and responses are be made available for download in pdf format – feel free to use them! If you’re a medical educator with a pedagogical problem, we want to get you a MEdIC. Send us your most difficult dilemmas and help the rest of us bring our teaching to the next level.

The Case of the Unexpected Outcome

by Drs. Justin Hensley  & Teresa Chan
Melissa Armstrong walked into the Emergency Department, readying herself to take on her third evening shift in a row. It’d been a long week so far, and she felt a bit tired, but that’s because she’d seen more than 60 patients in the past 2 shifts. But this was the curse of being a newly minted attending at a busy urban hospital. You took the shifts that were given to you.
Walking by the Physician’s station, she noted Mike gesticulating wildly at her.
“Hey!  Melissa!” he said, as Melissa walked over to him. “Remember that lady with chest pain from yesterday that you sent home?”
Melissa felt that niggling sensation in the pit of her stomach. Those were NEVER good words.
“Well, she came back in a this morning, and she was pretty sick. We had to intubate her and send her to the unit. It looked like she had a giant pulmonary embolism.”
Melissa thought for a second and said, “Wait, the 34 year old?”
Mike nodded.
“But she didn’t have any risk factors!”
Melissa quickly rushed to the office, and pulled up the chart. She found her note and read it.  She had outlined her diagnostic reasoning. She had thought the patient was low risk according to the Well’s PE score, PE rule out criteria (PERC) was negative, so she hadn’t ordered a D-Dimer.
Diagnosis: viral syndrome.
What had she missed?
Her stomach turned and she was hit by a wave of nausea.
“Hey… you’re looking pale,” stated Mike, escorting Melissa to a chair. “Sit.”
He disappeared momentarily, and returned with a glass of ice water.
“Drink.”
“But….She had a cough and a fever. Others in the family were sick. After meds, pt was feeling fine!” she sputtered. “Her vitals normal. Look, she’s Well’s low risk and PERC negative! What could I have done differently?”
“Well, all I know was what I saw this morning – tachycardic, hypotensive, D-Dimer of 6,400. Her CT-Pulmonary Angiogram showed a saddle embolism. If she didn’t have a PE yesterday, she definitely did this morning.”
“Dr. Armstrong… to Trauma bay 1. Dr. Armstrong…”
“Well, I guess it’s time to get to work, Melissa. They’re calling for you in Trauma. Come on, Melissa, shake it off!”
Melissa shook her head, trying to shake off the daze and walked over to the Trauma bay.
For the next 8 hours, went by quickly – but Melissa couldn’t shake that uneasy feeling in the pit of her stomach. Luckily, there were fewer patients than the day before. The major care patients weren’t an issue, but every viral illness in the quick care area, however, she found herself diligently documenting the Well’s, PERC and even ordered a few D-dimers in very low risk patients. Luckily, they all were negative.
At the end of her shift, she went upstairs to the intensive care unit to check on her patient from the day before.  The intensivist explained that the patient as doing better now that they had given her thrombolysis.

The next morning, Melissa awoke with that queasy feeling still in the pit of her stomach.  Her thoughts immediately jumped back to the case from two nights ago. What had she missed?
Picking up the phone, she called Kyle, her best friend from residency. Explaining the situation briefly over the phone, Kyle immediately insisted that he would be right over with coffee from her favorite neighborhood coffee shop.
Over a latte, Kyle had Melissa recount the story.
“I just don’t know what else to do. I feel like I can’t go back to work without people judging me, but to keep from missing things I feel like I have to over-investigate everyone so I don’t miss anything. Yesterday, I ordered 7 D-Dimers. I’m seeing PE everywhere. My confidence is just…. shot.”

Key Questions

Imagine you are in Kyle’s shoes.  How would you handle this?
  1. Melissa is obviously very upset about the case. How would you advise her to address her emotions?
  2. When applying evidence-based medicine, there are still times when there will be exceptions.  How do you handle those exceptions?
  3. Confidence plays a large role in our jobs as physicians.  How do you suggest Melissa proceed now that she is feeling very uncomfortable and second guessing herself?

Weekly Wrap Up

As always, we will post the expert responses and a curated commentary derived from the community responses one week after the case was published. This month the two experts are:
  • Dr. David Marcus  is the Chief Resident at the combined Emergency/Internal Medicine program at LIJ Medical Center in New York. He teaches Ethics, Professionalism, and Emergency Medicine at the Hofstra-North Shore LIJ School of Medicine. Dr. Marcus is a strong advocate of FOAM and other open educational resources. When not stalking the resuscitation rooms he can usually be found on Twitter or sailing Long Island Sound. Check out, which includes a list of international EM, Critical Care and Medical Education conferences.
  • Dr. Ryan Radecki is a board-certified Emergency Physician and Assistant Professor of Emergency Medicine at the University of Texas Medical School at Houston.  He blogs at  and is the principal of .  He practices Clinical Informatics, and develops tools to improve patient safety and support personalized medicine.  He is a member of the editorial staff of the Emergency Medicine Journal, and his work can be found in ACEP Now, and Emergency Physician’s Monthly.
Next week, you’ll be able to click here to go to the Expert Responses and Curated Community Commentary for the Case of the Unexpected Outcome (to be posted on May 24, 2014).
All characters in this case are fictitious. Any resemblance to real persons, living or dead, is purely coincidental.  Also, as always, we will generate a curated community commentary based on your participation below and on Twitter.  We will try to attribute names, but if you choose to comment anonymously, you will be referred to as your pseudonym in our writing.

Monday, May 12, 2014

Atypical Antipsychotic Medication Re-initiation in the Emergency Department

PillsThe acute episode of intoxication and agitation has subsided and your patient is calm. She has been medically cleared and is ready to be moved to a less acute, less monitored portion of the ED to await further assessment and treatment for her underlying psychiatric conditions. As a well-intentioned emergency medicine practitioner, you wish to give your patient the tools she needs to maintain this calm status by restarting her home atypical antipsychotic medication. What is the best way to go about doing this?
While the atypical antipsychotics have generally been considered safer than the first generation agents due to the decreased risk of extrapyramidal side effects at therapeutic doses, this class is not without adverse effects. All of the medications in this class are capable of causing sedation due to their antihistaminergic effects and some of these agents also have an alpha-blockade effect possibly leading to orthostatic hypotension [1].

Re-Initiation Strategy: Atypical Antipsychotic Medication

When faced with the prospect of re-initiation of atypical antipsychotics, it is necessary to determine how long the patient has been without medication if possible. While there is a lack of literature regarding this topic, select medications make reference to re-initiation in their package inserts [4,8,9].These recommendations range from “an interval off” to “more than one week”, possibly indicating that a few missed doses may not have an impact on the re-initiation dose. However, when it is determined that a patient has been without their atypical antipsychotic for a few days to a week or the period of nonadherence is unknown, caution with re-initiation is justified and some package inserts call for restarting the initial dosing titration.
Medication
Package insert: Day 1 dosing
Re-initiation recommendation
Aripiprazole (Abilify)Schizophrenia: 10-15 mg PO Q 24 hours
Bipolar mania: 15 mg PO Q 24 hours
Bipolar mania (adjunctive therapy): 10-15 mg PO Q 24 hours
No recommendations
Asenapine (Saphris)Schizophrenia: 5 mg PO Q 12 hours
Bipolar mania (monotherapy): 10 mg PO Q 12 hours
Bipolar mania (adjunctive therapy): 5 mg PO Q 12 hours
No recommendations
Iloperidone (Fanapt)Schizophrenia: 1 mg PO Q 12 hoursWhen off > 3 days, the initial dosing titration schedule should be followed
Lurasidone (Latuda)Schizophrenia: 40 mg PO Q 24 hours
Bipolar depression: 20 mg PO Q 24 hours
No recommendations
Olanzapine (Zyprexa)Schizophrenia: 5-10 mg PO Q 24 hours
Bipolar disorder: 10-15 mg PO Q 24 hours
No recommendations
Paliperidone (Invega)Schizophrenia: 6 mg PO Q 24 hours
Schizoaffective disorder: 6 mg PO Q 24 hours
No recommendations
Quetiapine (Seroquel)Schizophrenia: 25 mg PO Q 12 hours
Bipolar mania: 50 mg PO Q 12 hours
Bipolar depression: 50 mg PO Q HS
When off ≥ 1 week, the initial dosing titration schedule should be followed
Risperidone (Risperdal)Schizophrenia: 2 mg PO Q 24 hours
Bipolar mania: 2-3 mg PO Q 24 hours
When off for an interval, the initial titration schedule should be followed
Ziprasidone (Geodon)Schizophrenia: 20 mg PO Q 12 hours
Bipolar I disorder: 40 mg PO Q12 hours
No recommendations
*Dosing above is not adjusted for renal or hepatic dysfunction or concomitantly administered interacting medications

Clozapine

Due to the risk of agranulocytosis for which there is a black box warning, all patients prescribed clozapine must be enrolled in a registry which monitors the patient’s white blood cell count and absolute neutrophil count.  As a result, clozapine dosing must be made in collaboration with the patient’s clozapine registry. In addition, clozapine also carries a black box warning for cardiovascular and respiratory effects and states that for patients who have been without clozapine for 2 or more days, they are to start with 12.5 mg once or twice daily [11].

Other Agents

For other agents, the course of action is less clear. Dosing decisions should ideally be made in conjunction with a psychiatric care provider; however this is not always feasible in the ED setting. For patients on atypical antipsychotics without clear re-initiation instructions in the prescribing information and doses higher than initial dosing (see table), consider a dose reduction. Anecdotally, re-initiating the dose at 50-80% of the maintenance dose seems reasonable in hemodynamically stable patients; however, there are not identified data to support this strategy. Regardless of the strategy implored, vigilance is important when re-initiating atypical antipsychotics. This is especially noteworthy in patients who will be in a less monitored area of the department.

Take Home Points

  • Determine how long the patient has been without their atypical antipsychotic if possible.
  • Use caution when re-initiating home doses of atypical antipsychotic agents and consider dosing reductions in patients who have been without their medications for more than a few doses.
  • Clozapine must be ordered in conjunction with the patient’s clozapine registry and when off for 2 or more days usually requires restarting initial dosing.
  • When the maintenance dose is above the initial dosing and re-initiation instructions are not within the package insert, consider a dose reduction (such as restarting  50-80% of the patient’s stabilized dose, depending on the clinical picture) to avoid adverse events, especially in less monitored patients
Reviewer: Clayton English, PharmD, BCPP
Associate Editor: Bryan Hayes, PharmD, DABAT

References

  1. Minns AB, Clark RF. Toxicology and overdose of atypical antipsychotic. J Emerg Med. 2012;43:906-13.
  2. Abilify® [package insert]. Tokyo, Japan. Otsuka Pharmaceutical Co; 8/2013.
  3. Saphris® [package insert]. Whitehouse Station, NJ. Merk & Co; 2009. Rev. 3/2013.
  4. Fanapt® [package insert]. East Hanover, NH. Novartis Pharmaceutical Corporation; 1/2013.
  5. Latuda® [package insert]. Marlborough, MA. Sunovion Pharmaceuticals; 7/2013.
  6. Zyprexa® [package insert]. Indianapolis, IN. Eli Lilly & Company. 1997. Rev. 2013.
  7. Invega® [package insert]. Titusville, NJ. Janssen Pharmaceutical, Inc; 2007. Rev 1/2014.
  8. Seroquel® [package insert]. Wilmington, DE. AstraZenica; 2013.
  9. Risperdal® [package insert].  Titusville, NJ. Janssen Pharmaceutical, Inc; 2007. Rev 11/2013.
  10. Geodon® [package insert]. New York, NY. Pfizer; Rev. 1/2014.
  11. Clozapine [package insert]. Morgantown, WV. Mylan Pharmaceuticals Inc. 5/2013

Sunday, May 11, 2014

Deep Vein Thrombosis (DVT): Wells criteria and D-dimers happy together


DVTYou are evaluating a 45-year-old male who is complaining of calf pain. He has a history of cancer however he has never had a clot in the past.   The leg is neither swollen nor warm but he notes a cramping sensation in the posterior portion of his calf.  You are concerned for a deep vein thrombosis (DVT) and consider the multiple means to reliable exclude the diagnosis: Wells score, D-dimers, ultrasound? What works?

Deep Vein Thrombosis: Background

The concern when approaching a patient with potential DVT is for the downstream embolic complications particularly pulmonary embolism (PE).  In patients evaluated with a suspected DVT, the prevalence of thrombosis has been estimated to be 10-15% (1) demonstrating the low testing threshold of many physicians when encountering this diagnosis for fear of future morbidity. The role for peripheral testing, if it is to be useful particularly to exclude thrombosis, is to lower the 10-15% pre-test probability further to a reliable and predictable percentage conventionally considered to be safe. Currently a 2% miss rate is considered acceptable (2) and is therefore utilized as a safety metric by which to measure the usefulness of ancillary clinical and/or laboratory tests.

Wells Criteria

The Wells rule has been utilized as a clinical decision instrument to help physicians adjust patient risk based upon assessed clinical parameters. As a reminder, the criteria are as follows:
  • Active cancer (+1 point)
  • Bedridden recently >3 days or major surgery within four weeks (+1 point)
  • Calf swelling >3 cm compared to the other leg (+1 point)
  • Collateral (nonvaricose) superficial veins present (+1 point)
  • Entire leg swollen (+1 point)
  • Localized tenderness along the deep venous system (+1 point)
  • Pitting edema, greater in the symptomatic leg (+1 point)
  • Paralysis, paresis, or recent plaster immobilization of the lower extremity (+1 point)
  • Previously documented DVT (+1 point)
  • Alternative diagnosis to DVT as likely or more likely (-1 points)
Those with 0-1 points are deemed “low risk.” Combining the D-dimer with a Wells score seems to impart a low enough risk to not require further testing or the risk of empiric anticoagulation. However, there have been recent studies that question this strategy arguing that the risk is unacceptably high in this group and further that this strategy is useless in particular higher-risk subgroups (e.g. males, active malignancy, recurrent DVT).

Article Citation

Geersing GJ, Zuithoff NP, Kearon C, et al. Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis. BMJ. 2014 Mar 10;348:g1340. PMID: . [Free385 kb]
Objective
  • Meta-analysis of individual patient data from 13 diagnostic studies of patients with suspected DVT to determine the diagnostic safety of utilizing Wells criteria and D-dimers, specifically as they apply to different patient subgroups
Study Methods
  • Authors contacted principle investigators of included primary studies to obtain original patient data
  • Inclusion criteria for studies
    • Consecutive patients with suspected DVT
    • Dataset with Wells parameters
    • D-dimer results (if performed)
    • Reference standard for DVT
      • Compression ultrasonography or venography
      • Uneventful follow-up in 3 months
Results
  • 13 included studies: Canada, the Netherlands, U.S., Sweden
  • In the new constructed dataset: n=10,002 patients
    • Missing data
      • Five studies did not record D-dimer levels
      • <1% presence/absence of DVT
      • 5% “Alternative diagnosis as likely as or more possible than DVT”
    • 864 (19%) had proximal DVT
    • Median age: 59 years
    • Female: 62%
  • Lowest possible Wells score in isolation = -2 points
    • DVT rate = 5% (range 2.0-5.9%)
  • Wells score in isolation = 0 points
    • DVT rate = 7.9% (range 6.1-10.2%)
  • Low Wells score (≤1) + negative D-dimer test
    • DVT rate (a.k.a failure rate) = 1.2% (0.7-1.8%)
    • Worked for all subgroups EXCEPT those with a history of cancer
    • Excluding cancer, this approach would exclude DVT in 1 in every 3 patients with suspected DVTs

The Bottom Line

The study demonstrates that the strategy of combining a Well score + D-dimer was superior to Wells alone and would allow the exclusion of DVT in 1/3 of patients who presented with this scenario. Importantly, it was found that patients with a history of active malignancy continued to have an unacceptably high risk of DVT and were not able to be safely excluded utilizing this strategy. It has been demonstrated (3) that a targeted D-dimer strategy (that is risk-based D-dimer testing) is useful in the work-up in DVT and may preclude the need for ultrasonography. In the pooled data above 1 out of every 3 individuals who presented with a low risk Wells score (≤1) combined with a negative D-dimer would not require further testing.

Words of Caution

A few important points regarding the interpretation of this study must be raised however when analyzing the clinical implications.
  1. An extraordinarily low risk (<2%) was defined as a baseline safety metric in order to deem the testing strategy efficacious. Though the Wells+ D-dimer approach allows the reduction of risk amongst the cohort to <2%, the range of probabilities for low risk Wells scores alone (-2 to 1 point) were 2.8% to 12.8% respectively. In spite of the fact that safety was a priori defined as <2%, it is not clear that the reduction of risk from say 5% pre-test probability to less than 2% has any real clinical benefit.
  2. Interpreting the results in reverse, it will require that 2/3 patients undergo further testing in order to reduce the probability of one patient to < 2%.
  3. Intrinsic to the Wells score is a clinical assessment of the patient— if a singular assessment of “alternative diagnosis more likely” by a physician (with no other Wells findings) is associated with an at best 5% risk of DVT, then one could add a D-dimer in the hopes of reducing risk to <2% or be comfortable with what should be considered an extraordinarily low risk of disease based upon a more specific test (history and physical) than D-dimer. Phrased in a different fashion, clinical judgement alone (alternative diagnosis is more likely) risk stratifies individuals to such a reasonably low level that the net gains of additional testing would seem to be offset by the amount of false positives generated by further testing to reduce 3 percentage points. Though the current medical fashion suggests that we need to drastically reduce the risk of all patients at the expense of specificity it is not clear that in the aggregate we are doing more good than harm.

Future Directions

The study is intriguing both from its findings and its reflections of the current medical diagnostic quandaries. It would seem that the culture of diagnostic medicine, at least in the U.S., continues to be one of extraordinary discomfort with uncertainty, necessitating testing strategies that require unrealistic levels of performance. The trend of diagnostics continues to be a movement towards perfection finding every disease no matter how small the risk or trivial the disease at the expense of unnecessary work-ups and a multitude of false positives. A study like this, while helpful in some respects, demonstrates quite well our generation’s approach to diagnostic uncertainty. Clinically this study is intriguing and should be reproduced prospectively in order to confirm the findings of a pooled group of disparate studies.  The meta-analysis was extraordinarily well done but still subject to the statistical vicissitudes of lumped data from various studies pooled into one comprehensive dataset.