CRITICAL Care – End of Life in the ED

The Gist: Palliative care is an emerging field in Emergency Medicine and most of us are inadequately equipped to discuss end of life issues, death and dying, which are all quite common in the Emergency Department (ED) [1].  We often feel uncomfortable in these situations as our instinct remains - resuscitate first, ask questions later. In a community that values cutting edge, critical care medicine, I was stunned when I realized that Free Open Access Medical education (FOAM) has engendered me to think twice about a procedure and take the time to ascertain what a patient actually wants.

These FOAM resources changed my course as a budding Emergency Physician and made me realize how ill equipped I was to handle dying patients, despite the frequency with which I encounter them.  As such, I felt compelled to use my slot at our residency conference dedicated to critical care to discuss end of life issues with my colleagues.  Here it is as FOAM, since I hassle others to share their talks.


The FOAM
SMACC GOLD (iTunes)
EMCrit with Dr. Ashley Shreves "Critical Care Palliation"
The Geripal Blog - The Importance of Language

The Take Home
Run these ABCD's in tandem with our typical ABCs (Airway, Breathing, Circulation) because the trajectory that we launch patients on matters - whether it's to the ICU with an endotracheal tube, to dialysis with a line, or a palliative care consult [1, 6-9,15].

Advance Care Directives (does the patient have one?), Ask the patient/caregivers what they want.
  • Identify if a patient has a health care proxy or physician order for life sustaining treatment (POLST).  
  • Use appropriate language, avoid jargon.  The phrase, "Do Not Resuscitate (DNR)," is falling out of favor and major societies are now using the language "Allow Natural Death"[3]. Try replacing DNR with "It sounds like she would want a natural death."  
  • Dying patients, even those with DNR orders, Comfort Measure Only orders, or those with Do Not Hospitalize directives come to the hospital because dying is hard, uncomfortable, and stressful.  Figure out what they want and need, it's not always a tube or a line.
Better - Make the patient feel better
  • Turn off monitors or beeping pumps (especially if they're beeping), generously dole out opioids for dyspnea/pain, offer various means of respiratory relief (non-rebreather, nasal cannula, non-invasive ventilation).
Caregivers - identify the patient's caregivers and Communicate with all parties in appropriate language
  • As above, use appropriate language, avoid jargon.  My favorite phrase, effective on nearly all patients, "What is most important right now?"
Decisions - offer medically appropriate decisions in ways patients and caregivers can understand.  Aggressive resuscitation and cardiopulmonary resuscitation (CPR) are appropriate in many situations, but not all.  Think about the downstream consequences, positive and negative, of various courses of action.
  • The publics perception of CPR is largely misinformed and studies show that most people overestimate the success of CPR to hospital discharge.  One study of patients over 70 years of age found over half believed survival after CPR was >50% and 23% believed survival to discharge was >90% after CPR [2].  Furthermore, people may not understand that CPR does reverse the underlying process and a patient is typically sicker after CPR than they were before.  Let patients know the implications of these decisions.  For example, once someone dies, CPR involves chest compressions which often result in broken ribs but sometimes restart the heart.  There's no guarantee that if we restart the heart that we will get his/her brain function back.
  • If appropriate, offer more than one option and recognize the power and responsibility that comes with the entrusted title of physician.  People do listen to provider recommendations [5].  For example, some patients may want aggressive testing and treatment for etiologies of dyspnea, some may want oral antibiotics for a pneumonia if it may improve their shortness of breath, and some may opt solely for opioids. 
References:
1. Members of the Emergency Medicine Practice Committee.  Emergency Department Palliative Care Information Paper June 2012.   ACEP 
2. Adams DH, Snedden DP. How misconceptions among elderly patients regarding survival outcomes of inpatient cardiopulmonary resuscitation affect do-not-resuscitate orders. J Am Osteopath Assoc. 2006;106(7):402–4. 
3. Breault JL. DNR, DNAR, or AND? Is Language Important? Ochsner J. 2011;11(4):302–6. 
4. Cassel JB, Kerr K, Pantilat S, Smith TJ. Palliative care consultation and hospital length of stay. J Palliat Med. 2010;13(6):761–7. doi:10.1089/jpm.2009.0379.
5. Cook D, Rocker G. Dying with Dignity in the Intensive Care Unit. N Engl J Med. 2014;370(26):2506–2514. doi:10.1056/NEJMra1208795.
6. DeVader TE, Albrecht R, Reiter M. Initiating palliative care in the emergency department. J Emerg Med. 2012;43(5):803–10. doi:10.1016/j.jemermed.2010.11.035.
7. DeVader TE, Jeanmonod R. The effect of education in hospice and palliative care on emergency medicine residents’ knowledge and referral patterns. J Palliat Med. 2012;15(5):510–5. doi:10.1089/jpm.2011.0381.
8. Lamba S, Mosenthal AC. Hospice and palliative medicine: a novel subspecialty of emergency medicine. J Emerg Med. 2012;43(5):849–53. doi:10.1016/j.jemermed.2010.04.010.
9. Lamba S, Quest TE. Hospice care and the emergency department: rules, regulations, and referrals. Ann Emerg Med. 2011;57(3):282–90. doi:10.1016/j.annemergmed.2010.06.569.
10. Schmidt TA, Zive D, Fromme EK, Cook JNB, Tolle SW. Physician orders for life-sustaining treatment (POLST): lessons learned from analysis of the Oregon POLST Registry. Resuscitation. 2014;85(4):480–5. doi:10.1016/j.resuscitation.2013.11.027.
11. Wright A a, Keating NL, Balboni T a, Matulonis U a, Block SD, Prigerson HG. Place of death: correlations with quality of life of patients with cancer and predictors of bereaved caregivers’ mental health. J Clin Oncol. 2010;28(29):4457–64. doi:10.1200/JCO.2009.26.3863.
12. Wu FM, Newman JM, Lasher A, Brody A a. Effects of initiating palliative care consultation in the emergency department on inpatient length of stay. J Palliat Med. 2013;16(11):1362–7. doi:10.1089/jpm.2012.0352.

Dip the Tap? – Diagnosis of Spontaneous Bacterial Peritonitis at the Bedside

The Gist:  Study results of urine reagent strips for the bedside diagnosis of spontaneous bacterial peritonitis (SBP) are highly variable with sensitivities from 45-100%.  Some suggest that certain dipsticks, if at least Grade 3 positive, have a great positive predictive value and positive likelihood ratio; thus, initiating treatment for SBP is likely a good idea.  A negative result, however, cannot rule out SBP, and this test is subject to limitations such as which reagent strip one has, what qualifies as "positive," and the prevalence of SBP at that location.  Suspect SBP or sick patient? Give antibiotics.

Why the enthusiasm in the Emergency Department (ED)?
A bedside test for diagnosis of SBP is neat and could potentially help identify an infective source earlier than standard laboratory tests (ascitic fluid cell count of >1000 WBCs or >250 polymorphonuclear neutrophils (PMNs) [1].  This laboratory endeavor takes time and reagent test strips commonly referred to as "urine dipsticks" have surfaced as a candidate.  Some studies cite a time "savings" of 2-3 hours using these strips as one may start targeted antibiotics after the bedside test [6].  In an era of source control and "time to antibiotics" measures in sepsis, early diagnosis of SBP has potential benefit.
Photo: Nottingham Vet School
Typical reagent strips, like the one above, demonstrate different grades of positivity, indicated by the color of the individual block.  Here, the leukocytes are indicated by the box on the far left of the image in which presence of leukocytes is quantified by reaction via leukocyte esterase.  These are read at the bedside after a certain period of time elapses (often 1-2 minutes), either by a person or machine. The pictured stick has a negative (off white), Grade 1 (slightly less off white), Grade 2 (lavender), Grade 3 (darker lavender/purple).

One important lesson that Free Open Access Medical education (FOAM) has hammered home, however, is the importance of understanding how to use a test prior to adoption.  On a recent episode of FOAMcast, we discovered that the core text, Rosen's Emergency Medicine references the positive correlation between SBP and a "positive" dipstick [1].  Unfortunately, the text doesn't go into how specifically to use the test or limitations, which could potentially lead to misapplication.  As an excited resident, I might opt to test this trick of the trade out without investigating exactly how it could or should change my practice. Furthermore, major societies currently recommend against the use of these test strips [2,3].

The Early Literature Hype
The initial studies were promising and cited sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Values (NPV) of 100% [4].  These studies also had relatively small numbers (n=31-257) and were conducted in a variety of settings with limited ED patients [4].  A positive test, in the majority of studies, was any result other than negative.  Some authors, including Gaya et al, called for the ability to rule out SBP based on a negative dipstick (Multistix 10SG) [5].

The Shifting Tide:  The many studies that subsequently followed had varied results and few were conducted in the Emergency Department (ED).  These studies used a variety of strips (Multistix - most commonly tested, Nephur, Combur, Uriscan, Aution Combina, and Choiceline) and demonstrated widely variable predictive scores with sensitivities of approximately 65% in nearly half of the studies and one study with a sensitivity of merely ~45%.  The specificity in these studies, however, remained quite high at >90% [4].  This literature is summarized nicely in a meta-analysis by Nguyen-Khac et al.
  • Multistix (n=12 studies): Sensitivities ranged from 45.3-100%, with higher sensitivities when a lower grade was used as "positive" (64.7-100%) [4].
A more recent study that was not included in this analysis posed a head-to-head ED based comparison between Uri-Quick Clini 10SG and MultistixSG10 in a population with a relative high incidence of SBP - 21.9% (49/223 samples).  Both strips had comparable specificities in the ~98% range.  This study more accurately depicts the way in which one might use reagent test strips, the importance of understanding which strip one has access to and its test characteristics, and the authors emphasize that the test does not rule out or replace the cell count [7].
  • Uri-Quick Clini 10SG Sensitivity 79.6% (64-87); + LR 33.7 (13-90); - LR 0.22 (0.13-0.38)
  • MultistixSG10: Sensitivity 77.5% (64-88%); + LR 33.6 (12.66-89.91); -LR 0.23 (0.14-0.39)
Why the variation?
  • Strips calibrated for urine so they don't match up to the PMN threshold for SBP.  As a result, what qualifies as a "positive" test varies - some studies used any level of positivity as "positive" and some specified a particular "Grade." 
  • Reading times of reagent strips varies and may impact results.
  • Different types of strips - the matrix and enzymes in strips varies based on manufacturer which may affect performance.  The strips used (ex: Aution sticks with high sensitivity) are not universally available [4,7].
  • Subjective interpretation of strips - This is a potential problem; however, the interrater reliability (kappa) was 0.8-0.94 (excellent!) in the studies in which it was calculated [6,7].  This is also dependent on whether the stick is read by a human or a machine (spectrophotometry).  
  • Varying prevalence of SBP in studied population (7-20%) [4,6].
What Now?
  • A 2012 study out of Mexico by Uribe et al demonstrates the utility of reagent strip testing as a rapid rule in diagnosis for SBP in low resource settings, with the caution that it is not a "rule out" test [7].  
  • SBP is associated with great mortality indicative of a very sick population, with an estimated survival after a patient's first episode of 68.1% at 1 month and 30.8% at 6 months [8].  As a result, it's probably best to suspect SBP in any sick cirrhotic, understand the limitations of the clinical exam, and administer antibiotics early in these patients.  Even if these patients get a non-targeted dose of piperacillin-tazobactam, this antibiotic still covers most SBP (although agents of choice are typically cefotaxime 2 grams IV Q4-8 hours or ceftriaxone 2 grams IV Q24 hours) [8].
  • Look for use of reagent strips at the bedside in the future for SBP but, like any test, understand the variability, the limitations, and the ways that the test is usable in one's own ED. 
References
1.  Oyama L.  Chapter 90:  Disorders of the Liver and Biliary Tract.  Rosen's Emergency Medicine, 8e (2014).  pp 1186-1204.
2.  European Association for the Study of the Liver.  EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010 Sep;53(3):397-417.
3.  Runyon BA.  Management of Adult Patients with Ascites  Due to Cirrhosis: Update 2012.  (2013) doi: 10.1002/hep.00000
4.  Nguyen-Khac E1, Cadranel JF, Thevenot T, Nousbaum JB. Review article: the utility of reagent strips in the diagnosis of infected ascites in cirrhotic patients. Aliment Pharmacol Ther. 2008 Aug 1;28(3):282-8.
5. Gaya Dr, Lyon DB, Clarke J et al. Bedside leucocyte esterase reagent strips with spectrophotometric analysis to rapidly exclude spontaneous bacterial peritonitis: a pilot study. Eur J Gastroenterol Hepatol. 2007 Apr;19(4):289-95.
6.  Nousbaum JB, Cadranel JF, Nahon P, et al. Diagnostic accuracy of the Multistix? 8 SG reagent strip in diagnosis of spontaneous bacterial peritonitis. Hepatology 2007; 45: 1275–81.
7.  Uribe M, Vargas-vorackova F. Rapid diagnosis of spontaneous bacterial peritonitis using leukocyte esterase reagent strips in Emergency. 2012;11(5):696–699.
8.  O’Mara SR, Gebreyes K.  Chapter 83. Hpeatic Disorders, Jaundice, and Hepatic Failure. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7e. New York, NY: McGraw-Hill; 2011. p 566-574

TRIMming Transfusions

The Gist:  Transfusions aren't benign and Transfusion Related Immunomodulation (TRIM) may play a role in complications associated with transfusions.  Data suggest that allogenic blood transfusions (ABTs) may have immunosuppressive properties [1-6]. Yet, TRIM is a vague controversial entity without easily identifiable clinical markers or pathogenesis and is predominantly based on observational and animal data [3,8].   Keep this entity in mind, not withholding blood products when indicated, but when contemplating the risks and benefits for those patients with borderline indications.  Give the patient all the blood they need, but not one drop more.

Free Open Access Medical education (FOAM) sources have increasingly mentioned this entity, TRIM, over the past few years, including this recent Maryland Critical Care Project podcast.  On a recent FOAMcastwe reviewed the core content associated with adverse effects of transfusions; yet, we did not encounter TRIM overtly in the review of Rosen's and Tintinalli.  Thus, I needed to find out more about this entity I had only learned about through podcasts.

TRIM has not made its way into many classrooms, likely secondary to the lack of understanding of the clinical significance and etiology of TRIM.  The development of pneumonia in the weeks following a transfusion is more difficult to attribute to a single etiology than a hemolytic reaction occurring during the transfusion.  Furthermore, much of the data are observational are observational and animal based with uncertain clinical implications.  As we see transfusion triggers decrease with equivalent or superior outcomes, it may be helpful to keep an eye on TRIM and, when we are tempted to transfuse individuals who are just above the transfusion threshold or give 2 units of red cells empirically, recall that blood product transfusions are actually transplants.  Perhaps we should have the same obsession with transfusions as we do fluid responsiveness summed up eloquently in the words of Dr. Paul Marik, "give that patient all the fluid they need, but not one drop more."

Clinical effects attributed to TRIM

Increased risk of infection
  • Contamination of blood products with infectious particles is not common and ranges from 1 in 1-3 million for HIV and hepatitis C, to 1 in 2000 for bacteria in platelets [11].  Studies, including the recent JAMA meta-analysis by Rhode et al, demonstrate more infections in individuals with higher transfusion targets.  Thus, some postulate that the increase in infections is a result of the immunomodulatory effects of transfusions. 
Tumor growth/Cancer - The roots of this notion, particularly an association with lymphoma, lie in retrospective and observational studies [6]
  • Randomized controlled trials (RCTs) looking at leukoreduced blood products did not demonstrate an increase in cancer  [1,2,6]
Multi-organ failure - this is one of the effects we care about most clinically and studies of various quality demonstrate an association between multi-organ failure/short-term mortality and transfusion [1].
  • Studies confounded by the underlying severity of illness of the patients, which itself predisposes the patients to multiorgan failure. 
  • The most consistent effects of TRIM are in RCTs involving cardiac surgery patients [1]
Improved survival in renal transplants - In the 1970's, patients awaiting renal transplants were given one or more ABT, leading to increased graft survival [1].
  • Immunosuppressive pharmaceuticals such as cyclosporine have replaced this practice.
Decreased spontaneous abortions [2]

Pathophysiology of TRIM -   These are postulated theories and associations since the exact etiology isn't clear.  Texts tend to agree that TRIM is the result of a complex inflammatory and immunosuppressive happenings that may result from downregulation of cellular immunity, induction of humoral immunity, and altered inflammatory responses. TRIM may depend on:

Degree of contamination of transfused blood with leukocytes - this is one of the reasons the FDA recommends leukoreduction of all blood [12].  Transfusions with leukoreduced blood have demonstrated varying results.
  • The beneficial effects of TRIM have been attributed to donor dendritic cells (or Allogeneic Mononuclear Cells - AMCs), which may invoke a tolerance among recipient cells and downregulate T cells.
  • Leukocytes release reactive oxygen species and proteolytic chemicals that may cause an inflammatory cascade and tissue injury [1].
  • Not the the sole culprit as trials in which one group received leukoreduced blood do not consistently demonstrate a difference [2].
Soluble components or "mediators" - This includes things like histamine, cytokines, and proteins in the plasma or released from the white cell membranes and granules are released upon degradation.  Also, there's some thought that plasma contains soluble class I HLA molecules, which may be partially responsible.
  • These "soluble mediators" may inhibit proper T cell function and ability of neutrophils to work properly [1].  
  • Higher levels of cytokines such as IL-10 have been demonstrated in patients receiving more blood in the peri-operative period.  It's theorized that these cytokines, whether they're generated by the recipient in response to a stimulus or from the donor, play an immunosuppressive effect [7].
  • However, filtration of these products before storage has not demonstrate a difference in "TRIM effects" (OR 1.06 (0.91-1.24)p>0.05), indicating that these are not the sole mediator of TRIM [2]. 
Storage time - This is not an exact etiology but may amplify the effects of the above proposed mediators.  This is purported secondary to the release of soluble mediators during storage of blood products.  Some studies have found increased infection, morbidity, or mortality with older red blood cells (RBCs) but the totality of the literature is inconclusive. Most of the studies have small numbers, have differing definitions of "old" RBCs, and are retrospective or observational in nature; however, results from the RCTs ABLE and RECESS may clarify [13].
  • Leukocytes degrade during the first two weeks of storage and release chemicals called soluble mediators.  RCTs that filtered leukoreduced and non-leukoreduced blood still demonstrated an increased incidence of infection in the non-leukoreduced blood (OR 2.25 (1.12-4.25) p<0.05) [2]
  • Free Iron - blood undergoes a degree of hemolysis during prolonged storage, freeing iron which is biologically reactive.   
So, we're not sure precisely what TRIM is, whether TRIM is clinically significant, or what may cause TRIM.  The bottom line is that transfusions likely have effects beyond what we currently understand, so it is prudent to treat this type of transplant with respect.

References:
1. Vamvakas EC, Blajchman MA. Transfusion-related immunomodulation (TRIM): an update. Blood Rev. 2007;21(6):327–48. 
2. Blajchman MA, Vamvakas EC.  (2009).  Transfusion-related immunomodulation In Pamphilon DH (ed). Practical Transfusion Medicine (pp. 98-106).  Blackwell Publishing
3. Zimring JC, Nester T.  (2013). Transfusion Related Immunomodulation In Shaz BH (ed.) Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects, Elsevier Science, Chapter 69.
4.  Chen W, Lee S, Colby J, et al.The impact of pre-transplant red blood cell transfusions in renal allograft rejection. Rockville, MD, USA: Agency for Healthcare Research and Quality. Technology Assessment Report; Project ID RENT0610; 2012.
5. Scornik JC, Bromberg JS, Norman DJ et al. An update on the impact of pre-transplant transfusions and allosensitization on time to renal transplant and on allograft survivalBMC Nephrology 2013, 14:217 
6. Gilliss BM, Looney MR, Gropper MA. Reducing noninfectious risks of blood transfusion. Anesthesiology. 2011;115(3):635–49. 
7. Theodoraki K, Markatou M, Rizos D, et al. The impact of two different transfusion strategies on patient immune response during major abdominal surgery: a preliminary report. J Immunol Res. 2014;2014:945829. 
8.  Geiger T. Transfusion-associated immune modulation: a reason to TRIM platelet transfusions? Transfusion. 2008 Sep;48(9):1772-3.  doi: 10.1111/j.1537-2995.2008.01860.x.
9. Rohde JM, Dimcheff DE, Blumberg N et al. Health care-associated infection after red blood cell transfusion: a systematic review and meta-analysis. JAMA. 2014 Apr 2;311(13):1317-26. 
10. Sparrow RL. Red blood cell storage and transfusion-related immunomodulation. Blood Transfus. 2010;8 Suppl 3:s26–30.
11.Hillyer CD, Josephson CD, Blajchman CJ et al.  Bacterial Contamination of Blood Components: Risks, Strategies, and Regulation.  ASH Education Book January 1, 2003 vol. 2003 no. 1 575-589
12. Food and Drug Administration.   Guidance for Industry: Pre-Storage Leukocyte Reduction of Whole Blood and Blood Components Intended for Transfusion. U.S. Department of Health and Human Services, Center for Biologics Evaluation and Research.  September 2012
13.Aubron et al. Age of red blood cells and transfusion in critically ill patients.  Annals of Intensive Care 2013, 3:2

"I heard it on a podcast once.."

The Gist:  In the medical and clinical arenas, it may often be unwise to simply quote an expert as justification, whether it's an expert on a podcast or something heard at a national conference lecture.  Use Free Open Access Medical education (FOAM) as a springboard for deeper learning and consider eliminating the phrase "I heard this on a podcast.." from one's arsenal.
  • Note: This is not an evidence based post, rather it's entirely opinion from the powerful experiences I've had failing at using FOAM (and other traditional, peer reviewed sources) juxtaposed with successes.  
The Case:  A trainee at Janus General took care of a patient with hyperkalemia secondary to polypharmacy (spironolactone, ibuprofen, and TMP-SMX).  When admitting the patient, the attending asked why sodium polystyrene (kayexalate) had not been administered and requested it be given in the emergency department.  The trainee replied, with a smug voice, "Well, I heard on a podcast that we don't need to give this, so I'm not going to."

Issues:  Repeating an authority figure's opinion without due diligence can be dangerous, whether it's in a podcast, on a blog, or in a lecture hall.


Eminence versus evidence.  The post, The Matthew Effect, demonstrates examples of how sometimes things that are quoted, both in FOAM and the literature, aren't always as .

Local standard of care.  Practice patterns vary for a myriad of reasons including: health care delivery models, availability of resources, geography, the practice of consultants, the legal system, and patient expectations.  As a result, things heard from experts may not apply, may not work within the framework of the local system, or may take time to implement.  Thus, it's important to keep this in mind while simultaneously pushing for the best, evidence based care for our patients.

A Few Fixes
:
Effective learning involves hard work.  As such, these "fixes" relegate slightly more responsibility on the learner, or whomever is process and potentially using the information.  

Read.  Good podcasts and blogs cite the references for their assertions.  When one encounters a controversial or innovative bit of information from a podcast or blog, spend extra time processing the information as quality and an author's spin may vary.  Furthermore, the "cutting edge" components of podcasts are often rooted in core texts and these can be used for both perspective and leverage.  This post delves more into establishing our thresholds to change our clinical practice.
  • Example:  "As you're aware, literature such as the 2010 Cochrane review and the American College of Gastroenterology guidelines on proton pump inhibitors (PPIs)  in patients with upper gastrointestinal bleeds didn't show any patient oriented benefit.  So, while I think this patient needs admission for endoscopy and further management, I feel comfortable holding off on this intervention at this time."   
Pose a question.  It is fun to bust myths and “lyse dogma” yet this can be off-putting and interventions may not work or be appropriate within the local system or standards of care.  It’s often helpful to generate a discussion on the subject under investigation, regardless of the medium - a new article, blog, or heard on a podcast or conference.
  • Example:  "Some physicians, including some in the nephrology literature, question the efficacy and utility of sodium polystyrene compared with the other interventions we have - with some potential for harm.  How does that fit in here?" Or, "What do you think of this study by Sterns et al in the Journal of the American Society of Nephrology?" 
Disclaimer.  Often, the tacit information shared on podcasts precedes supporting literature, if it exists.  For example, in January 2011, Dr. Scott Weingart published a podcast on delayed sequence intubation (DSI).  In the podcast and lectures on DSI at national conferences, Dr. Weingart has given a clear disclaimer regarding the paucity of peer reviewed evidence on this topic.  Weingart's paper addressing DSI was published online in 2010, yet the print version surfaced over a year later in June 2011, with cases published by Lollgen et al and Schneider et al in 2013-2014.
  • Example:  "I think we should maximize pre-oxygenation in this patient and, while it's not an evidence based technique, some people such as Dr. Scott Weingart, suggest that there may be times when procedural sedation can help with pre-oxygenation as we prepare to intubate."  
The Real World:  Now, it is impossible to perform individual deep dives on every clinical topic.  We do need filters and reliable, trustworthy sources.  Sometimes it can be difficult to parse these out.   There are potential solutions in the FOAM world.  For example, Dr. Seth Trueger offers the following in jest, but it may be helpful to approach information that one counters with the assumption that the accuracy isn't always what it seems.

Also, an excellent new FOAM search-engine, iClickEM (still in beta-testing; however, I recommend getting on the waitlist), pairs peer-reviewed sources alongside a set of curated FOAM sources.  The engine also uses fancy algorithms to create relevant and trusted results.

Engage in dialogue with colleagues, mentors in training programs, or content experts.  Reference FOAM resources such as podcasts and blogs and cite these works appropriately.  Yet please, consider refraining from prefacing a statement with, "I read it on a blog" or "I heard it on a podcast once."  

Breadth and Length – Antibiotics in Uncomplicated Cellulitis

The Gist:  Many cases of uncomplicated, non-purulent* cellulitis can be treated with a five day course of oral antibiotics, such as cephalexin or dicloxacillin, without covering for MRSA.  The Infectious Disease Society of America (IDSA) and core emergency medicine texts support this recommendation, with provisions for extended coverage (duration and/or MRSA antibiotics) in high-risk or sicker patients [1-3]. Despite these recommendations, providers often prescribe lengthier courses with broader spectrum coverage, which may have lead to adverse effects, increased cost, or resistant microbes [4-6,8].

The Case:  A 38 year old female presents to the emergency department (ED) with right lower extremity erythema and warmth, progressing over the past four days.  She has no known trauma, no prior history of cellulitis or abscesses, and her history was remarkable for "borderline" diabetes, hypertension, and depression.  Vital signs are within normal limits and examination reveal a diffusely erythematous area of approximately 7 x 4 cm, warm to touch, with some edema but no induration or drainage.  This patient seems to be an ideal candidate for outpatient therapy.  Should the provider write for cephalexin for 5 days? 7 days? Does the patient also need TMP-SMX or clindamycin?

Despite revolutionizing medical care, antibiotics prescribed for skin and soft tissue infections are not benign as patients incur costs and may develop allergic reactions, yeast infections, antibiotic associated diarrhea, or provoke resistant pathogens.  In national survey data, antibiotics have been associated with nearly 1 in 5 ED visits for adverse drug events and more than 1 in 4 similar events in the pediatric population [5,6].  Antibiotics prescribed for skin and soft tissue infections have been associated with a large proportion of these events, at least in children [7].  As a result, there's an increasing emphasis on using appropriate antibiotics for the minimum duration needed to treat the infection.

Duration of therapy: In 2005, the IDSA issued a recommendation a 5 day course of treatment for uncomplicated cellulitis and this is offered up as an option in core EM texts [1,3,6].  However, many practitioners prescribe an initial 7-10 day course of treatment. Interestingly, the most recent iterations of both Tintinalli and Rosen's do not hazard a suggestion for antibiotic duration for any skin and soft tissue infections [2,3].

The five day recommendation** is based on study by Hepburn et al.  Outpatients presenting to the clinic or ED (n=121) with uncomplicated cellulitis were treated with levofloxacin for 5 days and then randomized (n=87), at a 5 day visit, to receive either 5 additional days of antibiotics or placebo. Patients were reevaluated at an appointment between days 10-14 and then at 28 days by telephone.  Treatment success was not different between groups, with 98% resolution in both arms [8].
  • Diabetes was not an exclusion criteria and was present in 5% (n=12) and 7% (n=16) in the treatment and placebo groups, respectively.
  • At the time of randomization (day 5), patients were allowed to have persistent erythema and warmth, as long as it had not worsened and seemed marginally improved.  This was somewhat subjective.  
  • Patients were enrolled within 24 hours of diagnosis and treatment so some patients received different antibiotics during the first 24 hours.  
  • Levofloxacin isn't routinely used for cellulitis in most populations. 
Choice of antibiotics:  Most non-purulent cellulitis is caused by streptococcus (strep), even in areas with a high prevalence of MRSA.  As such, the IDSA and core texts recommend targeting strep only for most uncomplicated, non-purulent cellulitis [1].  Literature suggests these low risk patients do no better on coverage for both strep and staph [9].  In higher risk patients or those with purulence that do require staph coverage, it is recommended that providers use anti-MRSA antibiotics in areas with high prevalence of MRSA [1-4].  Use of anti-MRSA antibiotics in high risk groups including those with history of MRSA, diabetic ulcers, systemic illness, IVDU, and other higher risk patients is less controversial and more broadly supported [1-4].

A study comparing monotherapy with cephalexin versus TMP-SMX have demonstrated that in systemically well, uncomplicated patients, cephalexin monotherapy suffices [9]. Review of the study. A trial comparing TMP-SMX, placebo, cephalexin, or combination was completed in July 2013, with no posted results at this time [11].

Of note, studies examining the microbiology of cellulitis may be skewed by selection bias, as staph and MRSA tend to cause more purulent infections which may be more likely to be cultured [12]. Furthermore, cultures are only indicated and, theoretically obtained, in the sicker patients and in those with comorbidities which may further also skew the results.

Do we prescribe antibiotics appropriately? Not commonly.
Hurley et al conducted a retrospective cohort study in Denver of ED patients and outpatients in 2010-2011 that measured the frequency of "avoidable antibiotic exposure." The authors defined "avoidable" antibiotics with a broad spectrum of gram-negative activity (beta-lactam/beta-lactamase inhibitor combinations, second, third, or fourth-generation cephalosporins, fluoroquinolones, carbapenems, or aminoglycosides); combination therapy (2 antibiotics or more); or treatment for more than 10 days.
    • n=364 of whom 155 had cellulitis
    • Only 7% (n=8) of patients with cellulitis received 5 days of antibiotics and 47% (n=54) received 10 or more days of antibiotics
    • 61% of patients with cellulitis received MRSA coverage [9]
Also, there's no benefit to a single dose of IV antibiotics in the ED and blood cultures aren't helpful in these patients.  On a more controversial note, a recent retrospective chart review by Paolo et al found that blood cultures may not significantly alter management in cases of complicated cellulitis as the contaminant rate (3%) was roughly equivalent to our true positive rate (4%).

*Complicated - varies by reference, but typically includes immunocompromised, those with signs of systemic illness, extremes of age, or diabetes.
Purulent - drainage or signs of abscess. History of abscess and eschar are also associated with staphylococcus (staph).  
**It's difficult to determine what, precisely, the 7 and 10 day historical attachments are based on other than history and familiarity.
    References:
    1.  Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis. 2005;41(10):1373–406. 
    2.  Kelly EW, Magilner D.  "Soft Tissue Infections."  Tintinalli's Emergency Medicine: A Comprehensive Study Guide.  7th ed. p 1017-1018.
    3 .Marx JA, Hockberger RS, Walls RM.  Rosen's Emergency Medicine , Eighth Edition. Chapter 137, 1851-1863.e1
    4. Meislin HW, Giusto G.  Rosen's Emergency Medicine , Seventh Edition. Chapter 135, 1836-1838. 
    5.  Shehab N1, Patel PR, Srinivasan A, Budnitz DS. Emergency department visits for antibiotic-associated adverse eventsClin Infect Dis. 2008 Sep 15;47(6):735-43. 
    6.  Bourgois FT, Mandl KD, Valim C et al.  Pediatric Adverse Drug Events in the Outpatient Setting: An 11-Year National AnalysisPediatrics. Oct 2009; 124(4): e744–e750.
    7. Goldman JL, Jackson MA, Herigon JC et al.  Trends in Adverse Reactions to Trimethoprim-Sulfamethoxazole.  Pediatrics. Jan 2013; 131(1): e103–e108.
    8. Hepburn MJ, et al. Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis.  Arch Intern med 2004; 164, 1669-1674
    9. Hurley HJ, Knepper BC, Price CS, et al. Avoidable antibiotic exposure for uncomplicated skin and soft tissue infections in the ambulatory care setting. Am J Med. 2013;126(12):1099–106. 
    10. Pallin DJ, Binder WD, Allen MB et al.  Clinical Trial: Comparative Effectiveness of Cephalexin Plus Trimethoprim-Sulfamethoxazole Versus Cephalexin Alone for Treatment of Uncomplicated Cellulitis: A Randomized Controlled Trial.  Clin Infect Dis. (2013) 56 (12): 1754-1762.
    11.  ClinicalTrials.gov: A Service of the U.S. National Institutes of Health (NCT00729937). 
    12.  Ray GT1, Suaya JA, Baxter R. Microbiology of skin and soft tissue infections in the age of community-acquired methicillin-resistant Staphylococcus aureus. Diagn Microbiol Infect Dis. 2013 May;76(1):24-30.

    We Don’t Know What We Don’t Know

    The Gist:  Overestimation of our level of mastery is common and is referred to as the Dunning-Kruger effect [1-3].  This effect persists in medicine and may have deleterious effects both at the bedside and in the training process [4-6].  Use of practice testing or simulation, metacognition, and the push of information to an individual may mitigate the dangers of unconscious incompetence by identifying areas of weakness and keeping the practitioner skilled.

    "Ignorance more frequently begets confidence than does knowledge" - Charles Darwin [6]

    The Case:  A 48 year old female with hypertension presented to Janus General with the sensation of the room spinning and feeling off balance for the past day.  The resident performed a head impulse, nystagmus type, test of skew (HINTS) exam, which demonstrated the presence of a saccade during the head impulse component. and determined that the patient likely had a central cause.  The patient was admitted to the hospital for questionable TIA/CVA workup, which was negative.
    • The problem: a saccade during the head impulse component is suggestive of a peripheral cause of vertigo.  While use of the HINTS exam by emergency providers has not been validated and is outside the bounds of this discussion, this example demonstrates the overconfidence of the resident in their skills and interpretation and the potential for perpetuation of this misunderstanding.  
    The Dunning-Kruger Effect - These researchers demonstrated a large discrepancy between the way incompetent people actually perform and the way they perceive their own performance level.  This discrepancy appears smaller for highly skilled individuals, who may underestimate their mastery. The studies demonstrating this effect often result in a graph akin to the one below.


    The Danger in Medicine - A little knowledge is a dangerous thing.  In medicine, a balance exists between the confidence to commit and act and the insight to see that we have uncertainty or lack the appropriate skill set.  In emergency medicine this line may be particularly difficult to walk as patients often require immediate intervention at times when data is limited, clouding certainty.
    • Diagnostic Error -  Overconfidence may result in premature closure, confirmation bias, or failure to use clinical aids such as practice guidelines or decision aids.  It turns out that compared with tempered attendings and insecure medical students, residents may be most susceptible to diagnostic overconfidence [8]. 
    • Unsafe Procedures - An attending once told me, "Procedures in emergency medicine exist to keep us humble."  After a novice learner's first string of successful intubations, it's tempting to believe we've become "good" at intubations.  However, this hubris may cause us to expose patients to harm if we take short cuts in preparation or fail to continue to maintain contingency plans.  Furthermore, in emergency medicine, we must be able to cue up live saving procedures at any moment that we may only see or perform once in a career.  Without accurate awareness of our competence, we may we fail to recognize that our skillsets are weak or a procedure/tools/kits have changed leading to suboptimal outcomes.  
    “Real knowledge is to know the extent of one's ignorance” – Confucius

    Mitigating the Effect
    • Practice Testing (or retrieval practice) - While the quality of the evidence is poor, Davis et al write that physicians are particularly not keen at assessing themselves [6].  As a result, we are unlikely to identify our areas of incompetence ourselves.  Assessment through practice testing, however, may identify weak areas in our knowledge base or skill set that we may otherwise not identify. In this way, we may decrease the discrepancy between what we think we know and what we actually know.
    • Simulation - Practice and rehearsal can identify weak areas in procedures or situations we may not often encounter or, conversely, give us the confidence in our ability to act when needed.  This doesn't require mannequins and computers - simply rehearsing procedures and scenarios in our minds works quite well.  Dr. Cliff Reid eloquently stated, “We have the most powerful, 3D, high-fidelity simulator in the known universe," reference the mental simulator.
    • Information Push - Most of us only review topics we believe we have previously mastered when we discover a weak spot in our understanding or make a mistake.  However, when information is pushed to the us, we encounter a wider array of information.  
      • Free Open Access Medical education (FOAM) serves as a prime example of the concept of information push, as topics collated in RSS aggregators such as Feedly and delivered by subscriptions to podcasts or twitter feeds cover information not intentionally sought by the learner.  So, while some find FOAM overwhelming, it can be used in an interesting way to strengthen the areas that we don’t know that we don’t know.
    • Metacognition - Awareness of weak points in our reasoning or systemic traps may help us overcome overconfidence, particularly with regard to diagnostics.  The post, Metacognition For the Pragmatist, discusses ways in which we can overcome our cognitive biases.  
    • Remain skeptical of the feeling of complete ease and mastery, which may cause to stop working and striving to improve.  In his talk “The Path to Insanity” at SMACC 2013, Dr. Scott Weingart advises that we "never assume your own excellence" [9]. 
    What's the underpinning of the Dunning-Kruger effect?
    • It's difficult to estimate the quality of one's performance.
    • Self-enhancement bias - We tend to think we're better than we actually are.  For example, very few bad drivers actually recognize the fact that they, in fact, are the poor drivers.
    • Regression to the mean - This explanation exists as one of the primary criticisms of the Dunning-Kruger Effect and argues that the effect may be, in part, statistical artifact.  When people are asked to evaluate themselves, incompetent people may simply regress toward the mean when asked to evaluate their own performance. On the other hand, people who have extremely high levels of performance, those who have mastery in a given area, are also less likely to underestimate their skills to the degree that those who are incompetent.
    “I know that I know nothing” – Socrates
    References:
    1. Dunning D, Heath C, Suls JM. Flawed Self-Assessment: Implications for Health, Education, and the Workplace. Psychol Sci Public Interes. 2004;5(3):69–106. doi:10.1111/j.1529-1006.2004.00018.x.
    2. Kruger J, Dunning D. Unskilled and unaware of it: how difficulties in recognizing one’s own incompetence lead to inflated self-assessments. J Pers Soc Psychol. 1999;77(6):1121–34. 
    3. Dunning D, Johnson K, Ehrlinger J, Kruger J. Why people fail to recognize their own incompetence. Curr Dir Psychol Sci. 2003;12(3):83–87. doi:10.1111/1467-8721.01235.
    4. Edwards RK, Kellner KR, Sistrom CL, Magyari EJ. Medical student self-assessment of performance on an obstetrics and gynecology clerkship. Am J Obstet Gynecol. 2003;188(4):1078–1082. 
    5. Hodges B, Regehr G, Martin D. Difficulties in recognizing one’s own incompetence: novice physicians who are unskilled and unaware of it. Acad Med. 2001;76(10 Suppl):S87–9.
    6.  Davis DA, Mazmanian PE, Fordis M, Harrison R Van, Thorpe KE, Perrier L. CLINICIAN ’ S CORNER Accuracy of Physician Self-assessment Compared A Systematic Review. 2006;296(9).
    7. Darwin C. 1871. The Descent of Man, and Selection in Relation to Sex, 1st edition. London: John Murray.
    8. Berner ES, Graber ML. Overconfidence as a cause of diagnostic error in medicine. Am J Med. 2008 May;121(5 Suppl):S2-23. doi: 10.1016/j.amjmed.2008.01.001.
    9. Weingart S.  EMCrit.  Podcast 105.  August 20, 2013.  Available at: emcrit.org/podcasts/path-to-insanity/