An evidence-based emergency medicine podcast. The Washington University Emergency Medicine Journal Club podcast provides an excellent way to keep up with the medical literature, improve patient care, and increase understanding of evidence-based medicine. Each month we ask a clinical or operational question pertinent to the practice of emergency medicine. We then discuss the four articles most relevant to that question in an attempt to determine the most evidence-based approach to patient care.
Working in TCC can be draining, and on one particularly busy afternoon, you begin to suspect your own sanity. After back-to-back cardiac arrest patients, you wonder if perhaps you should have done something less stressful with your life, like maybe become a lobster boat captain or an ice road trucker.
Your first code is a middle-aged female who suffered cardiac arrest while watching Alabama beat Clemson during the Sugar Bowl (yeah...that's right!!!). She was initially noted to be in ventricular fibrillation (VF), and remained so after three rounds of defibrillation. As she arrives in the trauma room, you immediately continue CPR and set up to shock her again. Your attending orders amiodarone, and even though you remember hearing that this may not be very effective, you realize it's not the time to argue. The patient ends up with ROSC and goes to the cath lab when her ECG reveals an anterior STEMI.
Your second patient is an elderly male who was initially found to be in PEA by EMS, but then later developed fine VF after three rounds of epinephrine en route. You shock him three times in the trauma room without effect, and once again your attending calls for amiodarone. After twenty more minutes of CPR, the patient reverts to asystole and the code is soon called.
You end up giving amiodarone twice more in your shift, once to a patient with new-onset a-fib who ends up getting admitted after not converting to a sinus rhythm, and later to a patient with stable, wide-complex tachycardia (which you're pretty sure was ventricular tachycardia [VT]), and you start to wonder if your attending owns stock in the company that makes it. You search online after your shift and find an excellent rundown on the limits of amiodarone on RebelEM, which prompts you to perform your own literature search.
PICO Question:
Population: Adults patients with either new-onset atrial fibrillation, hemodynamically stable ventricular tachycardia (VT), or cardiac arrest due to ventricular fibrillation (VF) or VT
Intervention: IV Amiodarone
Comparison: Placebo or any alternative antiarrhythmic
Outcome: Conversion to normal sinus rhythm, need for hospital admission, survival, functional neurologic outcome, hypotension.
Amiodarone, which was first approved by the FDA in 1985, became a mainstay of arrhythmia management after being added to the ACLS guidelines in 2000. At that time, amiodarone was recommended ahead of lidocaine for management of hemodynamically stable wide-complex tachycardia but was only included as a consideration for refractory VF and pulseless VT. In the 2010 update, amiodarone was recommended as a “first line anti arrhythmic agent” in refractory VF/pulseless VT, based on limited evidence for improved rates of ROSC and hospital admission. In addition, amiodarone been recommended for use in recent-onset AF for over twenty years (Hou 1995). Given the rise in prominence of procainamide use in AF (see Ottawa Aggressive Protocol by Stiell et al), and an increased focus on longer term outcomes in cardiac arrest, we decided to review evidence for a variety of amiodarone indications frequently seen in the ED.
Stable Ventricular Tachycardia
PROCAMIO, a small, multicenter randomized controlled trial conducted at several hospitals in Spain enrolled 74 patients with hemodynamically stable, wide-complex tachycardia and randomized them to receive either IV amiodarone or IV procainamide over twenty minutes. Major cardiac events (clinical signs of hypoperfusion, dyspnea, hypotension, or acceleration of heart rate) occurred less frequently among patients receiving procainamide (OR 0.1; 95% CI 0.03 to 0.6). These patients also had a much higher rate of cardioversion (OR 3.3; 95% CI 1.2 to 9.3). Unfortunately, this was a very small study in which only a fifth of the number of planned patients was actually enrolled. Despite this limitation, it seems reasonable to use procainamide as a first line agent for hemodynamically stable wide-complex tachycardia rather than amiodarone.
Recent Onset Atrial Fibrillation
Procainamide has been used successfully in the management of recent-onset AF, with a previously documented conversion rate of around 60%, occurring at a median of 3 hours following drug infusion (Stiell 2010). In one systematic review and meta-analysis comparing IV amiodarone to placebo and class Ic antiarrhythmics (Chevalier 2003), amiodarone did not have a significantly higher rate of cardioversion compared to placebo at 1 to 2 hours, but did have a higher rate at 6 to 8 and 24 hours. Compared to class Ic antiarrhythmics, amiodarone was less effective at 1 to 2 and 6 to 8 hours, but had similar efficacy at 24 hours. Cardioversion with amiodarone by 6 to 8 hours occurred in 48-62% patients (depending on the individual study), which is fairly comparable to previously reported rates for procainamide. Given the lack of studies comparing procainamide to amiodarone head-to-head, it seems reasonable to consider either drug, though concerns regarding hypotension with amiodarone may sway many to use procainamide instead.
Refractory VF or Pulseless VT
A recent multicenter, randomized controlled trial conducted at 55 EMS services in North America sought to compare the effectiveness of amiodarone, lidocaine, and placebo in patients with out of hospital cardiac arrest (OHCA) due to refractory VF/pulseless VT. After excluding patients whose initial rhythm was not VF or VT, 3026 patients were enrolled and evenly split between groups. The authors found no significant difference in survival to hospital discharge between patients receiving amiodarone and placebo (ARR 3.2%; 95% CI -0.4% to 7.0%) and no difference between those receiving lidocaine and placebo (ARR 2.6%; 95% CI -1.0% to 6.3%). Unfortunately, despite the large number of patients enrolled, the outcome was fairly rare, which resulted in relatively wide 95% CIs. As a result, a potentially clinically meaningful survival improvement (3.2% for amiodarone and 2.6% for lidocaine) could not be shown to be statistically significant.
In a follow-up study, the authors of the previous study also looked at those patients initially enrolled but excluded because VF/pulseless VT was not their initial rhythm (i.e. those patients with an initially non-shockable rhythm). Again, they did not observe any statistically significant difference in survival to discharge between the three groups (1.9% for the placebo group, 3.1% for the lidocaine group, and 4.1% for the amiodarone group). Also, despite not finding a statistically significant difference, the study was not sufficiently powered to detect a potentially clinically significant improvement in mortality of 2% with amiodarone. Given this limitation for the last two studies, and the lack of any downside in this subset of patients, it seems reasonable to continue amiodarone use for patients with refractory VF/pulseless VT for both OHCA and in-hospital arrest.
NG Lavage for GI Bleeds
Dec 08, 2017
Show notes
Journal Club Podcast #39: October 2017
A discussion of the controversial practice of shoving a tube down someone's nose and sucking out stomach contents...
It is a typical Saturday afternoon in TCC when you are roomed a patient with a history of COPD and GERD who appears short of breath. When they bring him back from triage in a wheelchair, you watch him shakily stand and transition to the stretcher, appearing dizzy when he does so. As you go in to greet the patient, you ask the nurse to get him started on the monitor. You can hear wheezing on your exam.
HR 116 RR 24 BP 88/54 Sat 100% Temp 36.3
During the review of systems, your patients embarrassedly admits to having several large bowel movements over the past two days that appeared dark and have progressively gotten more tarry throughout the day. He has had smaller episodes in the past, but nothing so large or frequent. He denies any vomiting, and specifically has had no hematemesis. DRE reveals black, heme positive stool.
His respiratory rate improves a little with a nebulizer, but he still appears short of breath. His labs are significant for a hemoglobin of 6.8, so you initiate your resuscitation. The patient’s vital signs improve slightly but do not normalize. When you hear back from your GI consult, he asks you to admit the patient for serial CBCs overnight after performing a nasogastric lavage.
However, you remember reading an editorial about NG lavage in evaluating GI bleeds in patients without hematemesis that was not entirely flattering. On top of that, you are concerned about worsening your patient’s already existing respiratory distress (or risk aspiration) if it is unnecessary. You decide to perform a quick search to see if there are any articles that might help you weight the pros and cons...
PICO Question:
Population: Adult patients with potential upper GI bleeding
Intervention: NG tube lavage
Comparison: No NG tube placement
Outcome: Mortality, transfusion requirement, need for surgery, gastric visualization at endoscopy, triage of patients
Search Strategy:
No formal search strategy was used. Two emergency medicine residents used multiple sources to identify articles that evaluated the use of NG lavage in potential upper GI bleeding with regards to any outcome.
Bottom Line
Considered to be one of the more painful procedures performed in the ED, nasogastric tube (NG) insertion is also associated with complication rates of 0.3% to 0.8% (Pillai 2005). NG tubes are often placed in patients with a known or suspected upper GI bleed, with potential goals of determining if the source is upper or lower, improving endoscopic visualization of the gastric fundus by lavage, and potentially triaging patients to urgent vs. non urgent endoscopy (particularly off hours). Unfortunately, very little evidence exists to support routine NG tube placement or lavage in these patients. We therefore sought to broadly evaluate the potential benefits of NG tube placement in patients with suspected or known upper GI bleeds.
One of the earlier studies performed sought to evaluate the predictive ability of NG lavage (NGL) in predicting the presence of a high risk lesion (spurting, oozing of blood, or a visible non-bleeding vessel) at endoscopy (Aljebreen 2005). A total of 520 patients with known upper GI bleeding were enrolled from the Canadian Registry of patients with Upper Gastrointestinal Bleeding undergoing Endoscopy (RUGBE). When considering a bloody NGL as a positive test (and coffee-ground, clear, or “other” aspirate as negative), the positive likelihood ratio (LR) was 2.00 and the negative LR was 0.68. When bloody or coffee-ground NGL was considered positive, the positive LR decreased to 1.20 and the negative LR decreased to 0.63. Overall, these likelihood ratios are quite poor, and would do very little to alter the probability of the disease, no matter the results.
Another study, conducted in Paris, France, compared NGL and erythromycin in terms of ability to clear the stomach and improve gastric visualization during endoscopy (Pateron 2011). In this randomized, controlled trial, 253 patients were randomized to either NGL until clear, a dose of IV erythromycin, or both NGL and erythromycin. The mean visualization score at the time of endoscopy was similar between all 3 groups, with no difference in duration of endoscopy, need for hemostasis, ability to identify the source of bleeding, or need for a second endoscopy.
A third study, undertaken in the West Los Angeles VA system, attempted to compare outcomes between patients with GI bleed who underwent NGL and those who did not (Huang 2011). This retrospective study included 632 patients, of whom 378 patients underwent NGL. The authors used propensity score matching to try and achieve prognostic balance between the two groups by balancing for several known confounding factors. Following propensity matching, two groups with 193 patients in each were compared. There was no significant difference in mortality (OR 0.84, 95% CI 0.37 to 1.92), mean length of stay (difference 0.80 days, 95% CI -1.4 to 3.0), need for emergency surgery (OR 1.51, 95% CI 0.42 to 5.43), or mean blood transfusion requirement (difference -0.18 units, 95% CI -0.98 to 0.62). Of note, significantly more patients in the NGL group underwent endoscopy (OR 1.71, 95% CI 1.12 to 2.62) and were more likely to undergo earlier endoscopy, suggesting that significant imbalance remained between the groups in spite of propensity matching. This finding significantly limits the internal validity of the study.
Finally, a systematic review was identified from 2010 that attempted to determine the accuracy of NGL in differentiating upper from lower GI bleeds in patients with hematochezia or melena without hematemesis (Palamidessi 2010). The authors identified 3 articles; unfortunately, one of these (Aljebreen 2005) did not actually address the question being asked, as it only included patients with upper GI bleeds. For the remaining two article, positive LRs were 4.74 and 4.44, while negative LRs were 0.2 and 0.65. As before, these likelihood ratios (with the exception of the negative LR of 0.2) suggest that the results of the test would do little to change the probability of an upper (or lower) GI hemorrhage.
In all, there is very little evidence to support the routine use of NG lavage in patients presenting to the ED with suspected upper GI hemorrhage. The only potential benefit not explored was the triage of patients to emergent, urgent, or non-urgent endoscopy, which would likely only be helpful during off hours. Given the poor ability of lavage to identify patients with high risk lesions, and given the significant discomfort associated with the procedure, this seems like a fairly soft reason to place an NG tube. Additional factors associated with poor outcomes in upper GI hemorrhage, such as older age, presence of upper GI malignancy, and variceal disease (Roberts 2012), in addition to signs of clinical instability may provide better triage of these patients, and should be considered prior to NG tube placement.
Contrast-Induced Nephropathy: Myth or Monster
Sep 30, 2017
Show notes
Journal Club Podcast #38: August 2017
A brief discussion on contrast-induced nephropathy and some of the evidence that suggests it may be as real as Sasquatch himself...
It was a clear black night, a clear white moon...and you're stuck working in EM-2 instead of out regulatin'! One of your patients is Ms. Z, a 52-year old woman with left lower quadrant abdominal pain. She's quite tender and has some localized guarding, but no rebound. Her WBC is 14.5. You're worried about diverticulitis, possibly with rupture and an abscess, and would like to get a CT scan, but her creatinine is 1.7, which is her baseline. Additionally, she has a history of diabetes and hypertension, and you worry about causing contrast-induced nephropathy (CIN) if you give contrast for the CT.
Your attending assures you that there's no such a thing as CIN, that it's as made up as Santa Claus and the Easter Bunny (EmLitofNote: The Latest Myth: Contrast-Induced Nephropathy; EMCrit: Do CT Scans Cause Contrast Nephropathy). As you fight back the tears, your childhood fantasies destroyed, you call the radiologist to discuss what to do. The radiologist shares your concerns and suggests that in this "not overly skinny" woman, contrast shouldn't be necessary.
Lo and behold, the CT shows uncomplicated diverticulitis, and Ms. Z goes home on oral antibiotics, her remaining nephrons safe and secure. But as you end your shift, eyes heavy with fatigue, you wonder: was your attending right about CIN (and the poor little Easter Bunny), or was the radiologist right to be concerned? You head home, crash, wake up refreshed, and begin to search the literature…
Intervention: Administration of intravenous contrast for enhancement of CT scan
Comparison: No contrast administration for enhancement of CT scan
Outcome: Acute kidney injury, chronic kidney disease, need for dialysis, mortality
Search Strategy:
An article published in a recent issue of Annals of Emergency Medicine (Hinson 2017) was chosen as the impetus for this journal club. A meta-analysis referenced in this article, along with two primary research studies, were chosen for inclusion as well.
Bottom Line:
Iodinated contrast media was once cited as the third most common cause of iatrogenic acute kidney injury (Hou 1983). Previous research on the incidence of contrast-induced nephropathy (CIN) associated with intravenous contrast for CT scans in the ED has found the rate to be around 11%, with much lower rates of severe renal failure (1%) and death due to renal failure (0.6%) (McDonald 2014). Other studies have reported similar rates (Mitchell 2007, Mitchell 2012).
The problem with these cohort studies is that while they demonstrate the incidence of AKI in patients receiving IV contrast, they do not necessarily establish contrast as the cause of the AKI. Patients receiving IV contrast typically have some issue requiring them to undergo CT scanning or angiographgy, and some percentage of these patients would develop AKI independent of contrast administration. As a result, several observational studies have been undertaken to compare the incidence of AKI and other outcomes in patients receiving contrast to the incidence in patients not receiving contrast.
While some older studies have demonstrated an increased incidence of AKI among patients receiving IV contrast when compared with controls (Heller 1991, Polena 2005) these studies have failed to control for potential confounders. Studies that have controlled for such confounder, typically using propensity score matching, have found no increased incidence of AKI, severe kidney failure, or death due to renal failure compared to patients not receiving contrast (McDonald 2014, Hinson 2017). A meta-analysis of all such studies, performed in 2013, similarly failed to demonstrate a statistically significant increase in the incidence of AKI (McDonald 2013).
While the bulk of data thus far does not suggest a clear association between IV contrast administration and acute kidney injury (AKA CIN), no randomized controlled studies have performed up to this point. While more recent studies have used methods such as propensity matching to help control for known confounding factors, these studies are not able to control for unknown confounders, and similarly have not controlled for potentially renal protective interventions undertaken after contrast administration (e.g. IV fluid administration and bicarbonate administration, withholding of potentially nephrotoxic drugs). It would therefore be difficult to advocate for a change in clinical practice without such randomized controlled trials.
There have been several barriers to performing such studies, including the assumption that IV contrast is harmful. The current evidence may help break that barrier, establishing that there is clinical equipoise regarding this issue, but other issues remain. Perhaps the most significant is the potential harm in withholding IV contrast in patients undergoing CT who would benefit from contrast enhancement, making it unethical to randomize patients to a non-contrast arm in such a study. Unfortunately, until further evidence is available, it seems prudent to consider withholding IV contrast in patients felt to be at high risk of developing AKI, with the caveat that in some emergent cases (i.e. possible aortic dissection), the risks of withholding contrast may outweigh the risks of developing kidney injury.
Controversies in the Diagnosis and Management of Cellulitis
Aug 02, 2017
Show notes
Journal Club Podcast #37: July 2017
A brief discussion of several of the controversies that have popped up in the last few years regarding the diagnosis and management of cellulitis...
You're moonlighting in a local ED one afternoon, when you encounter Mrs. X, a 40-year-old woman with rheumatoid arthritis, for which she takes Methotrexate. She was gardening three days prior to presentation when she suffered a small cut to her left ankle from a misplaced spade. The following day, there was some mild erythema around the wound, which has progressed. She now has redness, warmth, and mild swelling to the lateral ankle and distal calf, with no signs of lymphangitis and no fluctuance. The ankle joint moves easily and without pain. As she is afebrile and well appearing, you discuss with her PMD and send her out on Bactrim and Keflex, to cover both Strep species and MRSA.
The very next patient you meet is Mr. Y, a 50-year-old obese male with CHF. He has had swelling in both his legs for quite some time, chalked up in the past to chronic lymphedema and CHF, but now has redness and pain to both ankles and lower legs. Given the severity of the redness and swelling, you elect to treat the patient for cellulitis and order vancomycin, then place an admission order. The hospitalist muses that perhaps the patient has venous stasis dermatitis, but admits that it's probably worth treating for potential cellulitis.
Thinking back to both patients later in the day, you begin to worry about your treatment plans. Should the immunosuppressed woman have been admitted for her cellulitis? What factors make patients more prone to treatment failure? Do you always need to prescribe both Bactrim and Keflex for cellulitis (see IDSA guidelines for SSTIs)? And finally, could the second patient have had stasis dermatitis, and if so, did he really need antibiotics and admission? You decide to look into the evidence to try to answer these questions, and dive right into the literature...
PICO Question:
Given the nature of the journal club this month, no specific PICO questions was devised. Instead, we looked at several controversial issues surrounding the management of cellulitis, including diagnostic accuracy, antibiotic selection, risk factors for treatment failure, and prescribing practices.
Search Strategy:
Again, due to the nature of the journal club, no specific search strategy was undertaken. Recent high-impact articles were selected from the medical literature, some due to their highly controversial nature.
Bottom Line:
Cellulitis, a common skin infection, results in around 2.3 million ED visits in the US annually. This number has risen over the years with the increasing prevalence of community-acquired MRSA (CA-MRSA) (Pallin 2008). Despite these rising numbers, there remains significant controversy regarding the diagnosis and management of this common condition, in part due to the lack of objective diagnostic criteria, the presence of several hard to distinguish mimics (Weng 2016), and difficulties in determining the bacterial etiology in the majority of cases (Jeng 2010).
The most recent guidelines from the Infectious Diseases Society of America (IDSA) do not recommend adding MRSA coverage for the management of mild or moderate non-purulent skin and soft-tissue infections (i.e. cellulitis and erysipelas). The PGY-4 paper (Moran 2017) found that among patients treated as an outpatient for cellulitis, cephalexin alone resulted in similar cure rates to cephalexin plus trimethroprim-sulfamethoxazole, supporting the IDSA recommendations. However, it should be noted that this recommendation does not apply to patients with fever or leukocytosis, or in immunocompromised patients. In our PGY-2 paper (Pallin 2014), the authors determined, among other things, that 63% of patients with cellulitis were given antibiotic regimens that included CA-MRSA coverage. Unfortunately, they did not attempt to determine how many of these patients had criteria that would exclude them from the IDSA recommendation, but instead insinuate that nearly all of them were being treated inappropriately. They even go so far as to recommend using this as a reported quality measure for Medicare’s Physician Quality Reporting System, a suggestion that is both premature and potentially dangerous.
Our PGY-3 article (Weng 2016) went a step further, attempting to determine the costs associated with misdiagnosis of lower extremity cellulitis in the US. They report that 30.5% of patients admitted to the hospital with lower extremity cellulitis in their study were misdiagnosed, and that the majority of these patients did not require hospital admission. Using a literature review, they therefore determined that such misdiagnoses cost between $195 and $515 million dollars annually throughout the US. Unfortunately, all of these conclusion are based on a highly methodologically flawed retrospective study in which final diagnosis was determined by chart review out to thirty days post-discharge. It is quite likely that the retrospective conclusion of misdiagnosis was, in many cases, itself a misdiagnosis. Additionally, the authors offer no direction on how to avoid such proposed misdiagnosis, failing to consider the amount of data available 30 days after presentation that would not be available to the ED physician at the time of presentation (e.g. response to treatment), and fail to note that among misdiagnosed patients who were deemed not to require hospital admission at all (determined retrospectively by dermatologists), the mean length of stay was over 4 days! This information suggests that either these patients did, in fact, need to be admitted, or that the ability to differentiate cellulitis from “pseudocellulitis” did not become evident until several days of observation had passed. An editorial written in response to this review notes many of these issues, but also calls for improved diagnostic capabilities and discussion between the ED and admitting physicians (Moran 2017), which seems more than reasonable.
Our PGY-1 paper (Peterson 2014) found that fever (odds ratio [OR] 4.3), chronic leg ulcers (OR 2.5), chronic edema or lymphedema (OR 2.5), prior cellulitis in the same area (OR 2.1), and cellulitis at a wound site (OR 1.9) were all predictors failure of outpatient management of cellulitis.
All of this evidence suggests that cellulitis can be a difficult diagnosis fraught with controversy. Care should be taken when diagnosing lower extremity cellulitis, as there are many mimics that do not require antibiotics. Care should also be taken in those patients with risk factors for failed outpatient therapy, with close follow-up and good return precautions given to such patients. Additionally, improved adherence to current IDSA guidelines would likely result in use of fewer antibiotics with fewer adverse effects.
Diagnosis of Atraumatic Subarachnoid Hemorrhage
Jul 17, 2017
Show notes
Journal Club Podcast #36: June 2017 Dr. Chris Carpenter and Marco Sivilotti bridge the US-Canada border to bring us a new podcast on the diagnostic approach to atraumatic SAH... Click Tabs Below to Expand Articles: Article 1: Sensitivity of early brain computed tomography to exclude aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis, Stroke 2016; 47: 750-755). (http://pmid.us/26797666) Answer Key. Article 2: False-negative interpretations of cranial computed tomography in aneurysmal subarachnoid hemorrhage, Acad Emerg Med 2016; 23: 591-598. (http://pmid.us/26918885) Answer Key. Article 3: Spontaneous subarachnoid hemorrhage: A systematic review and meta-analysis describing the diagnostic accuracy of history, physical examination, imaging, and lumbar puncture with an exploration of test thresholds, Acad Emerg Med 2016; 23: 963-1003. (http://pmid.us/27306497) Answer Key. Article 4: Determination of a testing threshold for lumbar puncture in the diagnosis of subarachnoid hemorrhage after a negative head computed tomography: A decision analysis, Acad Emerg Med 2016; 23: 1119-1127. (http://pmid.us/27378053) Answer Key. Vignette: Mrs. Z. is a healthy 30-year-old female who presents to your emergency department 2-hours after onset of “the worst headache of my life” which peaked within 1 minute of onset but was not “thunderclap”. She describes the headache as diffuse with associated nausea, but no photophobia, neck stiffness, vomiting, focal motor-sensory deficits, or fever. She reports no recent viral or febrile illness, blunt trauma, travel history, or sick contacts. Nobody else at home or work has had a headache recently. Her immunizations are up-to-date and she denies any significant PMH including no history of migraine (or other) headache disorders, cerebral aneurysm, stroke, HIV or other immunocompromising disorder, pseudotumor cerebri, malignancy, bleeding diatheses, or meningitis. She denies recent alcohol use or any history of intravenous or illicit substance abuse. She has not tried any medications for her headache. She is a secretary and lives at home with her husband and 3 year old child. In the ED, her vitals are BP 106/55, P 58, RR 18, T 37.2°C, and 100% oxygen saturation on room air. She is in no acute distress, and her exam is unremarkable. As you consider the diagnosis of subarachnoid hemorrhage and await her CT, you weigh the value of a post-CT lumbar puncture. You recall a recent meta-analysis discussed on your favorite “podcast” Emergency Medical Abstracts (listen here) as well as an episode of McMaster’s Textbook of Internal Medicine (watch here) and wonder how other researchers and specialties interpret the best evidence. Realizing that there are two distinct questions for the ED diagnosis of SAH, you develop two PICO questions. PICO Question: PICO Question #1 Population: ED patients with sudden onset severe headache concerning for aneurysmal SAH (aSAH) Intervention: Computed tomography within 6 hours of symptom onset Comparison: No comparator Outcome: CT sensitivity, specificity, positive/negative likelihood ratio for aSAH PICO Question #2 Population: ED patients with sudden onset severe headache concerning for aneurysmal SAH (aSAH) Intervention: Lumbar puncture following unremarkable CT Comparison:No comparator Outcome: LP sensitivity, specificity, positive/negative likelihood ratio for aSAH Search Strategy: Using these PICO questions, you devise a PubMed search using Clinical Queries (diagnosis/broad) and the search term “aneurysmal subarachnoid hemorrhage” which identifies 2891 studies (see http://tinyurl.com/zrvgc3s) from which you select the 4 studies below from last year. Bottom Line: Needle in a Haystack Headaches represent about 2% of emergency department (ED) visits annually. While severe headache patients presenting with altered mental status, fevers, or associated trauma usually generate sufficient concern to justify further diagnostic evaluations, most other sudden onset headache cases ultimately prove to result from benign, non-life threatening causes like migraine headache. The myriad causes of sudden onset headaches include cough, exertion, and post-coital, but can also include potentially life-threatening conditions like sinus thrombosis, vascular dissection, intracerebral hemorrhage, vasospasm, and aneurysmal subarachnoid hemorrhage. [Landtblom 2002, Delasobera 2012, de Bruijn 1996, Pascual 1996, Dodick 1999] Observational studies indicate that migraine headaches are at least 50-times more common than SAH amongst ED headache patients, so SAH represents a needle in a haystack for a very common chief complaint. [Edlow 2003] Missed SAH diagnosis occurs between 12%-53% of cases with ED providers estimated to miss 5% of them. [Edlow 2000, Vermeulen 2007] Up to 80% of SAH cases result from a ruptured cerebral aneurysm. Other causes of SAH include low-pressure perimesencephalic bleeds, cerebral amyloid angiopathy, vasculitis, sickle cell disease, and cocaine or amphetamine abuse. [Carpenter 2016] One-fourth of aneurysmal SAH victims die within one-day and 50% of SAH survivors never return to work. Correctly identifying SAH early can reduce these adverse outcomes if subsequent neurosurgical interventions (coiling or clipping) occur emergently. [Schievink 1997] Therefore, the possibility of aneurysmal SAH must be considered in ED patients presenting with severe headaches. Understanding the SAH diagnostic evidence available for bedside evaluation, advanced imaging, and the role for lumbar puncture (LP) is therefore essential and the landscape is shifting. Non-Contrast Cranial CT Computed tomography (CT) became widely available for the evaluation of headache patients about 30 years ago. Early CTs were 4-slice and radiologists’ interpretative learning curves were steep. These early CTs were imperfect (sensitivity ~90%) for identifying small amounts of blood in the subarachnoid space, so textbooks, guidelines, and several generations of emergency medicine trainees advised against a CT-only approach to rule-out aneurysmal SAH. Instead, SAH could only be ruled out when a negative CT was followed immediately by a LP demonstrating cerebrospinal fluid (CSF) without either red blood cells or (at least 12 hours post-headache onset) xanthochromia. However, in 2017 there are three problems with that approach: (1) contemporary CTs are far better at identifying blood in the subarachnoid space; (2) LP’s frequently identify blood that is not in the subarachnoid space (traumatic LPs); and (3) CSF xanthochromia is not an accurate diagnostic test for SAH. A rule of thumb to define sufficient diagnostic accuracy to rule-in a disease as positive is likelihood ratio (LR+) > 10 or negative likelihood ratio (LR-) < 0.1 to rule-out a disease. Both Perry 2011 and Backes 2012 demonstrate acceptably safe CT accuracy for SAH when imaging is obtained within 6-hours of headache onset (summary LR+ 235, summary LR- 0.01). Beyond 6-hours CT is still accurate to rule-in SAH (summary LR+ 223) but less impressive to rule out SAH (summary LR- 0.07, 95% CI 0.01-0.61). These studies used neuro-radiologists to interpret the CT, which opens the question as to whether general radiologists’ accuracy would equate these studies. Recent studies indicate that general radiologists’ are just as accurate for the diagnosis of SAH as neuro-radiologists. Post-CT LP– Quantifying Benefits and Harms Most European hospitals use spectrophotometry to evaluate the presence or absence of xanthochromia, whereas 99% of North American hospitals use visible inspection. Recent meta-analyses indicate that visible xanthochromia can rule-in SAH (LR+ 25) but is less accurate to rule it out (LR- 0.22). At least four spectrophotometric methods to evaluate xanthochromia exist and most ED headache studies report different methods, but spectrophometry using any method doesn’t appear to be significantly better than visible xanthochromia to rule-in or rule-out SAH. [Carpenter 2016, Chu 2014] At a threshold of 2000 x 106 red blood cells per liter in the final tube of CSF collected, the LR+ is 10.3 and the LR- is 0.07 (95% CI 0.01-0.49). [Perry 2015] Importantly, up to 30% of patients experience worsening post-LP headache, in addition to the risks of post-LP back pain, epidural bleeding, and introduction of skin flora into the central nervous system. [Seupaul 2005] Patients are not the only reluctant participants in this exercise; physician barriers to routine post-CT LP include inadequate time in the busy ED and expectation of normal or non-diagnostic results in most patients (low diagnostic yield). In fact, up to 1 in 6 LPs are traumatic (blood detected from skin or superficial soft tissue, not from the subarachnoid space). Consequently, LP is not performed in over half of acute headache patients in whom a CT is obtained. [Perry 2010, Perry 2013] The ultimate objective is not to understand test accuracy; instead, the goal is to deliver the appropriate care to the right patients. How is a busy ED physician supposed to interpret all of these numbers and communicate with patients meaningfully to allow shared decision making? One approach to balance the harms and benefits of post-CT LP is to hypothesize test- and treatment-thresholds. The test-threshold describes the probability of a diagnosis (aneurysmal SAH) below which continuing to test for the diagnosis will harm more patients than it will help, whereas above the threshold additional testing will benefit more patients than will be harmed. This threshold is derived from the test accuracy (CSF xanthochromia or RBC), risk of the test (post-LP headache, infection, or epidural bleed), benefit of the treatment for those with disease, and harms of the treatment for those without disease (since false-positives will receive the treatment and have no possibility of benefit since they don’t actually have the disease). Based upon one recent diagnostic meta-analysis, the threshold at which post-CT LP would benefit patients is quite narrow (2-4% for CSF RBC or 2%-7% for visible xanthochromia). Doubling the risk of benefit and halving the risk of harm was used to further evaluate these thresholds and the thresholds didn’t change significantly. Still not convinced? Thinking about the benefit of LP alone (and neglecting the potential for harms associated with LP), the Number Needed to LP (NNLP) to identify one CNS infection in acute onset headache patients is 227 [Brunell 2013] while the NNLP to identify one additional aneurysmal SAH upon which neurosurgical intervention occurs and which was missed by CT within 6 hours ranges from 250 [Perry 2011, Sayer 2015] to 15200! [Blok 2015] Journal Club Discussion Between Neurosurgery & Emergency Medicine Here is the synopsis of the Journal Club discussion between Neurosurgery and Emergency Medicine, including Dr. Sivilotti the senior author of the PGY-III meta-analysis. PGY-I CT within 6 hours of thunderclap headache onset is sufficiently sensitive to rule out SAH without LP, if the CT is 16 slice or greater with cuts < 5mm. PGY-II Non-contrast head CT is an excellent test for ED headache patients in whom SAH is a concern, but like every other test that exists it is not 100% sensitive. Scenarios in which false negative CTs occur include imaging more than 6 hours after the onset of the headache, less severe bleeds (as measured by Hunt-Hess classification), anemia (Hg <10), and non-neuro-radiologists readers. In those scenarios, patient shared decision making about additional testing (CTA or LP) is warranted but should include informed consent about anticipated benefits and potential harms. PGY-III Less than one in 10 headache patients concerning for SAH are ultimately diagnosed with SAH in recent studies. While certain symptoms and signs increase or decrease the likelihood of SAH, no single characteristic on history/physical exam is sufficient to rule in or rule out SAH. Within 6 hours of symptom onset, noncontrast cranial CT is highly accurate, while a negative CT beyond 6 hours substantially reduces the likelihood of SAH. Based on anticipated treatment benefit of 80% with immediate aneurysmal SAH (aSAH) diagnosis, LP risk of 1% (including significant post dural headache, discomfort, and infection), and total (cancer + other) risk for angiography of 2%, LP would only be helpful in a pre-LP probability of aSAH range of 2-7% (if using visible xanthochromia) or 2-4% (if using CSF RBC > 1000). Therefore, LP appears to benefit relatively few patients within a narrow pretest probability range. Scenarios in which false negative CTs occur include imaging more than 6 hours after the onset of the headache, less severe bleeds (as measured by Hunt-Hess classification), anemia (Hg <10), and non-neuro-radiologists readers. In those scenarios, patient shared decision making about additional testing (CTA or LP) is warranted but should include informed consent about anticipated benefits and potential harms. With improvements in CT technology and an expanding body of evidence, test thresholds for LP may become more precise, obviating the need for a post-CT LP in more acute headache patients. Existing SAH clinical decision rules await external validation, but offer the potential to identify subsets most likely to benefit from post-CT LP, angiography, or no further testing. PGY-IV Decision analysis using accepted methods but sparse, low quality evidence-basis demonstrates post-CT LP test threshold that is significantly higher than the majority of ED headache patients in whom SAH is considered. Nonetheless, the similar test-threshold point-estimate for post-CT LP in comparison to Carpenter et al (which used very different methods to derive a test-threshold), indicates that current textbook and guideline recommendations (which advocate post-CT for everyone) merit revision. The discussion amongst the Journal Club attendees focused around two issues. 1) Some neurosurgeons expressed concerns about the risk of aneurysmal re-bleeding within 24 hours, which has been recognized to be about a 6% risk since observational studies were conducted in the 1950’s. Some of the neurosurgeons also noted that no test is perfect, so their traditional approach has been that more testing is generally better for patients and providers. Dr. Sivilotti made the point that attempts to attain diagnostic perfection (0% miss rate) leads to operational inefficiencies for the hospital and at eventually harms some patients. 2) Some noted uncertainty about how to derive the initial pre-test probability estimate by which to guide post-CT decision-making about the benefits vs. harms of LP. It was noted that the PGY-III meta-analysis included weighted average prevalence of SAH of 7.5% in recent prospective studies of headache patients in whom SAH is a concern. This meta-analysis prevalence is one evidence-based estimate of pre-test probability. The point was then made that the 7.5% probability of SAH falls within the 2%-7% range for which LP benefits outweigh risks, but the meta-analysis authors noted that the 7.5% prevalence estimate is pre-CT. Whether a CT is obtained less than 6-hours post-headache onset (summary LR- = 0.01 so post-CT probability of SAH = 0.1%) or later than 6-hours (summary LR- = 0.07 so post-CT probability of SAH = 0.6%). Either way, the post-CT probability of SAH is far below the lower margin of benefit (2%). The issue with CT diagnostic accuracy beyond 6-hours is the 95% Confidence Interval which extends to 0.61, so these situations require more careful contemplation and perhaps offer a role for CT angiography – a proposal to which neurosurgery eagerly agreed requires additional research at Washington University. Future Research Priorities Carpenter et al. was grounds for practice-change for many ED diagnosticians, but has also received criticism – mainly based on philosophical grounds. Is the role of emergency medicine to definitively rule-in or rule-out parti…
Risk of Delayed Traumatic ICH in Patients on Anticoagulation
Jun 27, 2017
Show notes
Journal Club Podcast #35: May 2017
After a brief interlude where I shamelessly self-promote my new novel, I talk about the risks of delayed bleeding in head injury patients on warfarin...
You are working a moonlighting shift at a local level II trauma center when you meet Mr. X, a 68 year old gentleman with a history of atrial fibrillation, for which he takes diltiazem for rate control and warfarin for anticoagulation. He sees his primary care physician on a regular basis and has his international normalized ratio (INR) checked once a week. It has been between 2.0 and 3.0 consistently for the last 6 months. This morning, while walking his dog, a rare crossbreed known as a great doodle (a cross between a great Dane and a poodle), he was tripped up by the leash and fell forward, striking his forehead on the concrete. He suffered no loss of consciousness, has a mild headache, and has had no nausea or vomiting. His wife states that he has had no altered mental status since the fall.
On exam he has a GCS of 15, a superficial abrasion to his forehead with a small 4 cm hematoma, no cervical spine pain or tenderness, and a normal neurologic examination. His INR today is 3.2. Being an astute reader of the literature, you remember that the studies on the Canadian Head CT rules excluded patients on anticoagulation, and proceed to order a head CT, which is read as normal by the attending radiologist (not a neuroradiologist).
After updating the patient’s tetanus booster you discharge him home in the care of his wife. That night after your shift, you begin to worry about your patient and his risk of delayed intracranial hemorrhage given his anticoagulant use. You also wonder if his risk would be higher if he were on one of the novel anticoagulants (rivaroxaban, apixaban, etc). Unable to sleep, you head online and begin to search the literature for answers.
PICO Question:
Population: Patients on anticoagulation therapy suffering minor head injury
Intervention: Observation and/or repeat CT scan of the head CT
Comparison: Discharge after normal initial head CT
Outcome: Risk of delayed intracranial hemorrhage leading to a change in management
Search Strategy:
A previous journal club covering delayed intracranial bleeding in the setting of anticoagulation was conducted in 2012 (http://emed.wustl.edu/Journal-Club/Archive/August-2012). The online archive was searched and two of the articles were chosen for inclusion. PubMed was searched using the terms anticoagulation AND “delayed intracranial hemorrhage”, resulting in 7 articles (http://tinyurl.com/y9yjn3go). Among these, a systematic review and meta-analysis was chosen as well as one of the articles included in the systematic review.
Bottom Line:
Traumatic brain injury results in just over 1.3 million emergency department (ED) visits, 275,000 hospitalizations, and 52,000 deaths annually in the United States alone, with an increase in the combined rate of ED visits, hospitalization, and death from 521 per 100,000 in 2001 to 823.7 per 100,000 in 2010 (CDC TBI Report). In elderly patients suffering a fall, long-term anticoagulation has been shown to increase not only the incidence of intracranial hemorrhage (ICH) compared to those not on anticoagulation (8.0% vs. 5.3%, p < 0.0001), but to also increase mortality in those with ICH (21.9% vs. 15.2%, p = 0.04) (Pieracci 2007). Additionally, the use of warfarin prior to blunt head trauma has been shown to increase mortality compared to those not taking anticoagulants, with an odds ratio of 2.008 (95% CI 1.634-2.467) (Batchelor 2012). Unfortunately, the rate of pre-injury warfarin use has been increasing in trauma patients in the US, from 2.3% in 2002 to 4.0% in 2006 (P < .001); in patients older than 65 years, use increased from 7.3% in 2002 to 12.8% in 2006 (P < .001) (Dossett 2011).
Given the increasing number of head injury patients seen in the ED, and the increase in concomitant anticoagulant use, the clinical dilemmas surrounding these patients have become more and more relevant. Studies in patients taking warfarin who suffer minor head injury have shown incidences of ICH ranging from 6.2%-29% (Li 2001, Gittleman 2005, Brewer 2011), leading some authors to conclude that most, if not all, such patients should undergo routine cranial CT scanning on presentation (Brewer 2011, Cohen 2006, Fabbri 2004). One important question surrounds the prognostic implications of a normal cranial CT in head injury patients on anticoagulant therapy. While some European guidelines suggest that all anticoagulated patients with head injury should be admitted for a period of routine observation (Vos 2002, Ingebrigtsen 2000), these recommendations are not based on studies of the prevalence of delayed ICH.
In the three primary studies reviewed, the incidence of delayed ICH following normal CT scan in patients taking warfarin ranged from 0.6% to 6%; the meta-analysis revealed a pooled risk of 0.6%. However, if a diagnosed ICH has no affect on the patient’s outcome or treatment, then it would be considered a surrogate outcome, which is often “used as a substitute for a clinically meaningful endpoint that measures directly how a patient feels, functions or survives (Thomas 1995).” As such outcomes are often found to be clinically insignificant, their use has been questioned in the literature (Guyatt 2011, Fleming 1996), and the incidence of patient important outcomes should be considered instead. In these studies, the majority of patients found to have delayed ICH required no neurosurgical intervention and had no adverse outcome documented. The incidence of death or neurosurgical intervention ranged from 0 to 1.1%, with a pooled incidence of 0.13% in the meta-analysis.
The authors of one of the articles reviewed suggest that “our data support the general effectiveness of the European Federation of Neurological Society’s recommendations for 24-hour observation followed by a repeated head CT scan for anticoagulated patients with a minor head injury” (Menditto 2012). However, this conclusion is based on the incidence of delayed ICH (6%) rather than the incidence of clinically important outcomes (1.1%). In this study, only one patient out of 87 suffered clinically significant delayed ICH. It is mentioned in the study that one patient showed signs of neurologic deterioration, however they do not say if this was the same patient who required neurosurgical intervention. If so, this would suggest that observation alone would suffice to detect any clinically significant delayed ICH.
Additionally, the authors do not perform a cost-effectiveness analysis to support their conclusion. In a subsequent editorial appearing in the same journal, it is suggested that a protocol of 24-hour observation and routine repeat CT scanning would cost an average of just over $1 million per patient saved (Li 2012). The author of the editorial suggests that home observation and phone call follow-up would be more cost-effective, and likely as safe, though this has not been studied.
While the current literature does not support routine hospital observation for 24 hours or repeat cranial CT scans in all anticoagulated patients with head injury, this may be warranted in those at increased risk of delayed bleeding, such as those with supratherapeutic INR levels or concomitant antiplatelet therapy. Further studies are needed to identify these higher risk patients for delayed bleeding to determine appropriate management. Furthermore, as newer anticoagulants enter the market and begin to replace warfarin, such as apixaban, dabigatran, and rivaroxaban, further studies on the risk of delayed hemorrhage may be necessary to determine the best management strategy for patients on these medications.
Blood Pressure Management in Spontaneous Intracerebral Hemorrhage
Nov 23, 2016
Show notes
Journal Club Podcast #34: October 2016
A short discussion of optimal blood pressure management in ICH, looking at intensive BP control vs. guideline-based control...
It's a slow Sunday morning in TCC when you get a page that a fifty-year-old patient with a sudden onset of confusion is en route. Per the page, the patient's BP is 210/110, with a heart rate of 85. The patient arrives to the ED awake, alert, but clearly confused. He answers all questions inappropriately and only follows commands with repeated questioning. His BP is still elevated (208/113).
After getting a finger-stick blood sugar, which is 105, a normal ECG, and sending off labs, you rush the patient for a head CT. The CT shows an intraparenchymal hemorrhage in the left basal ganglia without intraventricular extension. The volume of blood is about 30 mL.
You immediately place a consult to neurology while the patient is transported back to the room. The nurse rechecks the patient's BP, which is now 218/115, and asks what you would like to do to treat this hypertension. You remember learning that when managing BP in intracerebral hemorrhage (ICH) there is a balance between reducing further bleeding and perfusing the rest of the brain, but you aren't sure what the optimal goal BP is or how quickly you should try and achieve this goal. After discussing this with the neurologist, you decide to do a quick literature search and see what the evidence shows...
PICO Question:
Population: Adult patients with spontaneous ICH and elevated BP
Intervention: Aggressive lowering of blood pressure
Comparison: Standard lowering of blood pressure (i.e. SBP below ~180 mmHg)
Outcome: Death, functional status, quality of life, cost, length of stay
Search Strategy:
A PubMed “Clinical Queries” search was performed using the terms “intracerebral hemorrhage” AND “blood pressure” with category set to Therapy and scope to Broad. The search was then limited to studies published in the last 5 years using human subjects (http://tinyurl.com/zhj7zgs). This strategy resulted in 143 articles, of which 3 randomized controlled trials and 1 meta-analysis were chosen. The Cochrane database of systematic reviews was also searched, but did not identify an additional meta-analysis.
Bottom Line:
Optimal blood pressure management in patients with spontaneous intracerebral hemorrhage (ICH) is complicated by the balance between hematoma size and cerebral perfusion. An association between maximum systolic blood pressure and hematoma enlargement has been shown (Ohwaki 2004), but must be tempered by the opposing risk of reduced cerebral blood flow with overly aggressive reductions in blood pressure (Butcher 2003). A small study published in 2013, however, found no difference in relative perihematoma blood flow in patients treated with more aggressive BP goals (SBP < 150 mmHg) compared to traditional goals (SBP < 180 mmHg). This finding opened the door to further clinical research on the effects of aggressive BP lowering in ICH.
In 2010, the AHA guidelines for management of ICH suggested that in patients with significantly elevated blood pressure (SBP > 180 or MAP > 130), a “modest reduction” in BP should be considered (SBP < 160, MAP < 110). This arbitrary BP goal was challenged in 2013 by the publication of the INTERACT2 trial. This seminal trial compared traditional BP management to more intensive BP lowering (goal SBP < 140 mm Hg within one hour), and found no statistically significant improvement in the primary outcome of functional status. The authors performed a post hoc analysis of the data, however, and did find an improvement in functional status using the newly popularized “ordinal analysis” of the data. This finding spurred further debate, resulting in additional studies on this subject.
A meta-analysis published in 2014 sought to shed further light on this subject, pooling the results of the INTERACT2 trial with its pilot study (INTERACT1), the ICH ADAPT study, and one additional study that lacked the funding to devise a kickass acronym. This meta-analysis confirmed the results of the INTERACT2 trial, which is far from surprising when you consider that the vast majority of patients (~85) came from that particular study.
Earlier this year, the ATACH-2 trial was published. Using similar methodology to the INTERACT2 trial investigators, the authors of this international, multi-center trial also found no statistically significant improvement in functional outcomes with more aggressive BP reduction, thereby confirming the prior results of INTERACT2 and the pursuant meta-analysis.
Medical Expulsive Therapy (Tamsulosin) for Ureteral Colic
Oct 27, 2016
Show notes
Journal Club Podcast #33: September 2016
A brief discussion of the growing literature on the use of tamsulosin (and sometimes nifedipine) in ureteral colic...
You are working in TCC one busy evening, kicking ass and saving lives. In the middle of the primary survey of a critically ill level one trauma, you are suddenly hit by a sharp, 10 out of 10 pain in your right side. Thinking that Doug Schueurer might have punched you, you turn around swiftly and see that he is on the other side of the room. After the patient is stabilized, you run to bathroom and begin vomiting. Dr. Wagner knocks on the door and tells you to quit being dramatic and get back to work, which you faithfully do.
The pain continues though to the end of your shift, at which time you check yourself in as a patient. You vitals are stable, with a heart rate of 105. You have some improvement in your pain with IV morphine and toradol. Your creatinine is normal and your UA shows a moderate amount of blood, with no signs of infection. An ultrasound (which you remember from a previous journal club is useful for diagnosing ureteral stones) reveals a 4 mm stone in the right distal ureter with mild hydronephrosis.
After tolerating a PO challenge (and yes, eating one of our turkey sandwiches is a challenge), you are ready to home. You leave with prescriptions for zofran, vicodin, and Flomax. Having heard horror stories about people developing orthostatic hypotension while taking Flomax, you wonder if there is any real efficacy. When you get home, you decide to do a literature search and see what the evidence shows.
PICO Question:
Population:Adult patients with ureteral stones not requiring urgent surgical intervention
Outcome: Time to stone passage, pain level, need for surgical intervention, quality of life, patient satisfaction
Search Strategy:
The articles chosen for the 2008 journal club were reviewed, and the meta-analysis used at that time was chosen as one of the articles. PubMed was then searched using the terms “tamsulosin AND (stones or colic)” limited to the last 10 years (http://tinyurl.com/jj8qysm). This results in 167 studies, of which 3 relevant randomized controlled trials were selected.
Bottom Line:
In 2008, the Washington University emergency medicine journal club looked at the efficacy of medical expulsive therapy in the management of ureteral stones. The conclusion at that time, based largely on a systematic review and meta-analysis from the Annals of EM the year before, was that tamsulosin and nifedipine may “improve moderate sized (more than 5mm) distal kidney stone expulsion rates compared with standard medical therapy.” This review did suggest the need for further large randomized controlled trials to further evaluate this topic, given that the results were based largely on “Low-quality RCT’s.”
Since then, several larger RCT’s have been performed. One study with mostly small stones (70% being 2-3 mm in diameter) found that tamsulosin did not improve time to stone expulsion or need for urgent intervention (Vincendeau 2010). This finding was supported by a subsequent trial in which ~75% of stones were < 5 mm in diameter (Pickard 2015). Despite a trend toward improved spontaneous stone passage at 4 weeks (the primary outcome) in patients with stones > 5 mm in size receiving tamsulosin, the authors of this paper haughtily conclude that “further trials involving these agents for increasing spontaneous stone passage rates will be futile.” Ignoring this advice, an additional study was recently published in Annals of EM (Furyk 2016). While this study also did not demonstrate improved stone passage when considering all patients (absolute risk reduction 5.1%; 95% CI -3.0% to 13.0%), a prespecified subset analysis of patients with stones 5-10 mm in diameter resulted in a significant improvement in this outcome (ARR 22.4%; 95% CI 3.1% to 41.6%; NNT = 4.5.)
This body of data, overall, suggests that tamsulosin likely provides no benefit to patients with small kidney stones (i.e. those smaller than 5 to 6 mm in diameter), but does seem to provide benefit in larger stones. A recent meta-analysis that includes all of these studies came to a similar conclusion (Wang 2016). For patients with stones 5-10 mm in diameter, this meta-analysis found an ARR of 22% (95% confidence interval 12% to 33%) with a NNT of 5.
Anticoagulation of Isolated Calf DVTs
Oct 03, 2016
Show notes
Journal Club Podcast #32: August 2016
A quick review of the literature on anticoagulation in isolated below the knee DVTs, and why we still don't have an answer...
Mr. M is a 53-year-old patient with a history of high blood pressure and high cholesterol who flew back to St. Louis from Shanghai five days ago. Two days after getting back he noted pain and swelling in his left calf, which he thought was due to a muscle strain while getting off of the airplane. Since then, the swelling has remained constant while the pain has worsened slightly. He reports a dull ache that is worse with ambulation and improves with rest. He denies shortness of breath or chest pain.
On physical exam his vitals are normal, his lungs are clear, and he has a normal S1 and S2 without a cardiac murmur or gallop. He has mild swelling noted to the left calf with focal calf tenderness. There is no erythema, warmth, or induration, and his pulses are symmetric bilaterally.
Concerned for a possible DVT given his recent long flight, you obtain lower extremity dopplers which reveal echogenic material in the peroneal and soleal veins consistent with acute DVT, but no signs of DVT proximal to the calf.
You call the patients PMD to discuss management, and she recommends sending the patient home with no therapy because, "It's just a calf DVT. You don't treat those." While you understand that has been the classic teaching, you also remember listening to an ERCAST Podcast in the last couple of years that spoke about the controversy surrounding this dogma. You send Mr. P home and recommend repeat dopplers in 5-7 days, but later decide to search the literature in order to make your own evidence-based decision...
PICO Question:
Population: Adult patients with isolated calf DVT distal to the popliteal veins
Intervention: Therapeutic anticoagulation (heparin, low molecular weight heparin, factor Xa inhibitor, direct thrombin inhibitor, or vitamin K antagonist)
Comparison: No anticoagulation.
Outcome: Propagation of clot to the popliteal veins or beyond, PE, bleeding, death, cost, patient satisfaction, quality of life.
Search Strategy:
An advanced PubMed search was conducted using the strategy “calf AND (thrombosis OR DVT) AND anticoagulation” (http://tinyurl.com/hx4onng) with 180 articles resulting. From these, the four most relevant articles were chosen.
Bottom Line:
The management of DVTs isolated to the calf veins has remained a controversial topic for many years. The 2008 guidelines produced by the American College of Chest Physicians (ACCP) recommended long-term (3 month) anticoagulation for all patients with DVT, regardless of proximal extension. Updated ACCP guidelines produced this year, on the other hand, make no specific recommendation, offering options of either treating or not treating isolated calf DVTs, as long as surveillance ultrasounds are performed. This lack of a firm recommendation seems based less on actual evidence, as it is on the low quality of evidence, which we will review.
This clinical conundrum has persisted for decades, with research extending at least into the 1980s. In 1985, Lancet published a randomized, controlled trial from Sweden (Lagerstedt 1985), in which patients with DVT isolated to the calf vein (as detected by phlebography) received either warfarin or no further anticoagulation (following a 5-day course of IV heparin in both groups). With 52 patients randomized, the authors found that the risk of recurrent clot was significantly lower in the warfarin group, with a NNT of 3.5 (95% CI 2.2 to 8.5). Unfortunately, this does not seem to be a very patient-centered outcome, and no patient in either group developed a PE.
In 2010, an article published in the Journal of Vascular Surgery (Schwarz 2010) randomized patients with isolated calf muscle vein (soleal or gastrocnemius) DVT to naroparin or compression therapy alone. They found no difference in progression of clot into either deep calf veins (peroneal or posterior tibial) or proximal veins, with a RR of 0.98 (95% CI 0.14 to 6.7). Unfortunately, this small study was poorly reported and failed to adhere to CONSORT guidelines, making assessment of internal validity nearly impossible. Additionally, the inclusion of calf muscle veins only, which may be less likely to propagate or result in PE, would not detect benefit in patients with deep calf vein clot.
A recent pilot randomized, controlled trial conducted in the UK (Horner 2014) randomized patients with any isolated calf DVT to either warfarin or anti-inflammatory medication. Seventy patients were analyzed, and for the composite outcome of proximal propagation, symptomatic PE, VTE-related sudden death, or major bleeding, they found a statistically nonsignificant trend towards benefit with anticoagulation (absolute risk reduction 11.4%, 95% CI -1.5% to 26.7%). Although the study was small, it was designed to demonstrate the feasibility of a much larger study, which is currently underway. Such a study will provide the best evidence to date regarding this treatment.
The most recent evidence on this subject was a retrospective observational study conducted at UC Davis. Outcomes of patients with isolated calf DVT were assessed based on whether or not there was an intention for them to receive any form of anticoagulation. The composite outcome of proximal DVT or PE was less likely in those treated with anticoagulation (RR 0.36, 95% CI 0.15 to 0.84). This benefit persisted after adjustment was made for several confounders. Unfortunately, observational studies are never able to control for the unknown confounders, and such evidence does little to inform us of whether anticoagulation provides any actual benefit. Also, less than half the patients in the study underwent repeat testing to assess for propagation of DVT, and such testing was more likely to occur in the control group, biasing the results in favor of the treatment group. The study also included primarily inpatients, and less than 4% were from the ED.
The evidence reviewed here is notably lacking in large, randomized controlled trials of good methodology, making it difficult to make firm recommendations. The current Chest guidelines make sense given this lack of evidence, and the decision to treat or not treat isolated calf DVTs should be based on several factors, including location (muscle vs. deep veins), need for ongoing immobilization, and bleeding risk. Emergency physicians will have to work closely with primary care physicians and admitting teams when making such decisions, given the controversy surrounding this topic.
High Sensitivity Troponins
Aug 10, 2016
Show notes
Journal Club Podcast #31: July 2016
A short monologue on the advantages and disadvantages of high sensitivity troponins and a 0/1 hour algorithm to rule-out and rule-in MI...
You are working your first ever shift as an intern in the Barnes-Jewish Emergency Department on July 1st when you encounter Mrs. P, a forty-year old woman whose chief complaint is chest pain. She reports that 1 hour prior to arrival, while sitting at her desk at work, she developed a sharp, stabbing pain in the left side of her chest. The pain was not worse with deep inspiration or with exertion, but has continued since then. It is currently rated a 7 out of 10 and has not radiated or migrated. She notes mild subjective shortness of breath and denies diaphoresis or lightheadedness.
Mrs. P tells you she a history of hypertension and high cholesterol and takes amlodipine and atorvastatin. She has never had any cardiac issues, but her father had his first MI in his early seventies. Her ROS is negative except as noted above and physical exam is completely normal, including no tenderness to palpation of the chest, no leg swelling, and no calf tenderness. Her ECG has already been performed and is normal, and her initial troponin (ordered in triage) is < 0.03.
After discussion with your attending, you decide she is low risk enough that you can forego a stress test, but your attending does think you should keep her for a repeat troponin to rule out MI. Since her pain began so recently, your attending suggests waiting the prerequisite 6 hours before doing so. As you explain this to the patient, she is baffled at why she has to wait so long. As you explain that it takes time for troponin to reach detectable levels in the bloodstream, you remember that the sensitivity of troponin has increased with newer assays, and that in Europe they use an ultra-high sensitive troponin. You wonder if using such an assay would allow you to rule out MI more quickly without adding the risk of missed disease. After your shift, you head to Google and being your search...
PICO Question:
Population: Adult patients presenting to the ED with chest pain
Intervention: One-hour serial troponin using a high sensitivity assay
Comparison: Traditional 6-hour (or 4-hour or 3-hour or 2-hour) serial cardiac enzymes
Outcome: Missed MI, major adverse cardiac event (MACE), or death
Search Strategy:
An advances PubMed search was performed using the terms troponin AND high-sensitivity AND myocardial infarction, all limited to article title (http://tinyurl.com/zluqok8). This resulted in 106 articles, from which the following four were chosen.
Bottom Line:
Chest pain is a one of the most common chief complaints among patients presenting to emergency department (ED) in the US, representing around 5% of all ED visits. Despite widespread testing, around 2-3% of patients with myocardial ischemia or infarction are discharged home from the ED, and missed MI accounts for more malpractice dollar awarded than any other single diagnosis. It is likely that risk of malpractice lawsuits has at least in part led to the high admission rates for chest pain seen in the US, which ranges from around 40% to as high as 80% in some institutions according to data from medicare beneficiaries. This is in spite of data suggesting that only 13-23% of patients presenting to the ED will ultimately have a diagnosis of acute coronary syndrome.
The most recent AHA guidelines suggest that patients with symptoms suggestive of myocardial infarction should have serial cardiac troponin I or T levels drawn at presentation AND 3 to 6 hours after symptom onset to detect any rise in the level over that time. However, high-sensitivity troponin assays used in Europe have shown the potential to allow a more rapid rule-out/rule-in approach in which serial enzymes are checked only 1 hour apart. This approach could potentially lead to more rapid disposition of patients from our already overcrowded EDs. The European Society for Cardiology (ESC) has already embraced these newer troponin assays, incorporating a 0/1 hour algorithm into their recommended diagnostic approach. We sought, therefore, to review the evidence supporting these high-sensitivity troponin assays and their use in 0/1 hour algorithms.
The four studies identified were all very similar in design. Two of the studies assessed troponin I assays (Jaeger 2016, Neumann 2016) while two assessed troponin T assays (Mueller 2016, Reichlin 2015). All four studies used some kind of algorithm with specific cut-offs for the assay as well as cut-offs for the change in value between 0 and 1 hour. Using the cut-offs, patients were either assigned a “rule-in” status, a “rule-out” status, or were considered to be in a gray zone if could not be placed in either of these groups. For example, the two studies evaluating high-sensitivity troponin T used the following definitions:
• Patients with initial hs-cTnT < 12 ng/L and Δ1 hour < 3 ng/L were assigned to rule out status.
• Patients with initial hs-cTnT ≥ 52 ng/L and Δ1 hour ≥ 5 ng/L were assigned to rule in status.
• All other patients were considered to be in the observation group.
Use of this algorithm (and similar algorithms in the articles evaluating high-sensitivity troponin I) resulted in high negative predictive values for ruling out patients in all 4 studies, ranging from 98.9% to 100%, and allowed anywhere from 39% to 63.4% of patients to be ruled out within one hour. The positive predictive values for ruling patients in were significantly lower, ranging from 70.4% to 87.1%.
While this evidence suggests that use of high-sensitivity troponin assays would allow the rapid rule-out of many patients presenting to the ED with chest pain, there are some valid concerns remaining. These include the relatively low positive predictive values of the algorithms (which may lead to unnecessary procedures such as cardiac catheterization), and the lack of a clear plan for patients in the observation or gray zones (which may again lead to inappropriate testing in these patients). Additionally, the articles themselves are prone to significant bias, in part because of the heavy use of industry funding in all four studies (Ioannidis 2016). In all of the studies, for example, the adjudicated final diagnosis was based primarily on the results of the serial high-sensitivity cardiac troponin assays themselves, raising the specter of incorporation bias.
Most importantly, the current evidence is limited to providing negative and positive predictive values for the various algorithms. Future studies will need to assess the clinical impact of using the algorithms on decision making, disposition times, and patient outcomes in order to demonstrate efficacy and safety. It likely the lack of such studies that has kept these algorithms out of our practice in the US, and out of the AHA guidelines.
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