Sunday, May 20, 2018

Lit Bits: May 20, 2018

From the recent medical literature...

1. New Stroke Literature

A. Tenecteplase better than Alteplase before Thrombectomy for Ischemic Stroke

Campbell BCV, et al. N Engl J Med. 2018 Apr 26;378(17):1573-1582.

BACKGROUND: Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion.

METHODS: We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage.

RESULTS: Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group.

CONCLUSIONS: Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset.

B. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset

Thomalla G, et al. N Engl J Med 2018 May 16 [Epub ahead of print]

Intravenous thrombolysis with alteplase, a recombinant tissue plasminogen activator, is the standard medical treatment for acute ischemic stroke within 4.5 hours after the onset of symptoms. In 14 to 27% of strokes, the time of symptom onset is not known, frequently because stroke symptoms are recognized when the patient awakes from sleeping. Such patients are generally excluded from treatment with intravenous alteplase, and only some of them are candidates for mechanical thrombectomy.

A substantial proportion of strokes that are evident after sleep probably occur in the last few hours before awakening, which would be within the approved time window for the use of intravenous thrombolysis. Magnetic resonance imaging (MRI) in patients with stroke with a known time of symptom onset has identified the presence of a visible ischemic lesion on diffusion-weighted imaging, combined with the absence of a clearly visible hyperintense signal in the same region on fluid-attenuated inversion recovery (FLAIR), as predictive of symptom onset within 4.5 hours before imaging. We conducted the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial to determine whether treatment with alteplase would improve functional outcomes in patients with an unknown time of stroke onset and a mismatch between diffusion-weighted imaging and FLAIR findings on MRI.

Under current guidelines, intravenous thrombolysis is used to treat acute stroke only if it can be ascertained that the time since the onset of symptoms was less than 4.5 hours. We sought to determine whether patients with stroke with an unknown time of onset and features suggesting recent cerebral infarction on magnetic resonance imaging (MRI) would benefit from thrombolysis with the use of intravenous alteplase.

In a multicenter trial, we randomly assigned patients who had an unknown time of onset of stroke to receive either intravenous alteplase or placebo. All the patients had an ischemic lesion that was visible on MRI diffusion-weighted imaging but no parenchymal hyperintensity on fluid-attenuated inversion recovery (FLAIR), which indicated that the stroke had occurred approximately within the previous 4.5 hours. We excluded patients for whom thrombectomy was planned. The primary end point was favorable outcome, as defined by a score of 0 or 1 on the modified Rankin scale of neurologic disability (which ranges from 0 [no symptoms] to 6 [death]) at 90 days. A secondary outcome was the likelihood that alteplase would lead to lower ordinal scores on the modified Rankin scale than would placebo (shift analysis).

The trial was stopped early owing to cessation of funding after the enrollment of 503 of an anticipated 800 patients. Of these patients, 254 were randomly assigned to receive alteplase and 249 to receive placebo. A favorable outcome at 90 days was reported in 131 of 246 patients (53.3%) in the alteplase group and in 102 of 244 patients (41.8%) in the placebo group (adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P=0.02). The median score on the modified Rankin scale at 90 days was 1 in the alteplase group and 2 in the placebo group (adjusted common odds ratio, 1.62; 95% CI, 1.17 to 2.23; P=0.003). There were 10 deaths (4.1%) in the alteplase group and 3 (1.2%) in the placebo group (odds ratio, 3.38; 95% CI, 0.92 to 12.52; P=0.07). The rate of symptomatic intracranial hemorrhage was 2.0% in the alteplase group and 0.4% in the placebo group (odds ratio, 4.95; 95% CI, 0.57 to 42.87; P=0.15).

In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days.

C. AHA Rescinds Large Sections of New Stroke Guidelines

Sue Hughes. Medscape. April 27, 2018

In a somewhat bizarre turn of events, the American Heart Association (AHA)/American Stroke Association (ASA) has rescinded its recently released stroke guidelines, publishing a "correction" in which large parts of the document have been deleted.

A new paper, published online in Stroke on April 18, states: "Based on recent feedback received from the clinical stroke community…the American Heart Association/American Stroke Association has reviewed the guideline and is preparing clarifications, modifications, and/or updates to several sections in it. Currently, those sections, listed here, have been deleted from the guideline while this clarifying work is in process."

The AHA/ASA adds: "After review, a revised guideline, with consideration given to the clarifications, modifications, and/or updates of the sections noted above, will be posted over the coming weeks."

The sections that have been deleted are the following:

Section 1.3: EMS Systems Recommendation 4
Section 1.4: Hospital Stroke Capabilities Recommendation 1
Section 1.6: Telemedicine Recommendation 3
Section 2.2: Brain Imaging Recommendation 11
Section 3.2: Blood Pressure Recommendation 3
Section 4.3: Blood Pressure Recommendation 2
Section 4.6: Dysphagia Recommendation 1
Section 6.0: All subsections

The rescinding of the guidelines was done without the agreement of the Guideline Writing Committee. 

Chair of the Guideline Writing Committee, William J Powers, MD, H Houston Merritt Distinguished Professor and Chair, Department of Neurology, University of North Carolina at Chapel Hill, told Medscape Medical News: "This action by the AHA was carried out against the strongly voiced opposition and without the agreement of the majority of the 2018 Acute Ischemic Stroke Writing Group."

He added that he was "surprised and disappointed" by the way the AHA/ASA had handled the situation.

Commenting for Medscape Medical News, Mark Alberts, MD, chief of neurology, Hartford Hospital, Connecticut, said, "I don't think this has ever happened before. This is a challenging and unfortunate situation.  It's not good for anyone — the AHA, the guidelines writing committee, or the patients." 

The remainder of the essay:

The corrected AHA/ASA guidelines are here:
Powers WJ, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018;49:e46-e99

2. Children Who Receive Sedation Despite Not Meeting Fasting Guidelines Do Not Experience Increased Adverse Events

Key Points
Question  Does the duration of preprocedural fasting alter the risk pulmonary aspiration and associated adverse outcomes in children undergoing emergency department procedural sedation?

Findings  In this study of 6183 healthy patients undergoing sedation in 1 of 6 geographically separate and nationally representative Canadian emergency departments, 2974 (48.1%) did not meet fasting guidelines prior to sedation. Data analysis failed to identify an association between preprocedural fasting of any duration and any type of adverse event, and there were no cases of clinically apparent pulmonary aspiration.

Meaning  Delaying sedation to meet established fasting guidelines appears not to improve sedation outcomes for children in the emergency department.

Importance  It is not clear whether adherence to preprocedural fasting guidelines prevent pulmonary aspiration and associated adverse outcomes during emergency department (ED) sedation of children.

Objective  To examine the association between preprocedural fasting duration and the incidence of sedation-related adverse outcomes in a large sample of children.

Design, Setting, and Participants  We conducted a planned secondary analysis of a multicenter prospective cohort study of children aged 0 to 18 years who received procedural sedation for a painful procedure in 6 Canadian pediatric EDs from July 2010 to February 2015. The primary risk factor was preprocedural fasting duration. Secondary risk factors were age, sex, American Society of Anesthesiologists classification, preprocedural and sedation medications, and procedure type.

Main Outcomes and Measures  Four outcomes were examined: (1) pulmonary aspiration, (2) the occurrence of any adverse event, (3) serious adverse events, and (4) vomiting.

Results  A total of 6183 children with a median age of 8.0 years (interquartile range, 4.0-12.0 years), of whom 6166 (99.7%) had healthy or mild systemic disease (American Society of Anesthesiologists levels I or II), were included in the analysis. Of these, 2974 (48.1%) and 310 (5.0%) children did not meet American Society of Anesthesiologists fasting guidelines for solids and liquids, respectively. There were no cases of pulmonary aspiration. There were 717 adverse events (11.6%; 95% CI, 10.8%-12.4%), of which 68 (1.1%; 95% CI, 0.9%-1.3%) were serious adverse events and 315 (5.1%; 95% CI, 4.6%-5.7%) were vomiting. The odds ratio (OR) of occurrence of any adverse event, serious adverse events, and vomiting did not change significantly with each additional hour of fasting duration for both solids (any adverse event: OR, 1.00; 95% CI, 0.98 to 1.02; serious adverse events, OR, 1.01; 95% CI, 0.95-1.07; vomiting: OR, 1.00; 95% CI, 0.97-1.03) and liquids (any adverse event: OR, 1.00; 95% CI, 0.98-1.02; serious adverse events: 1.01, 95% CI, 0.95-1.07; vomiting: OR, 1.00; 95% CI, 0.96-1.03).

Conclusions and Relevance  In this study, there was no association between fasting duration and any type of adverse event. These findings do not support delaying sedation to meet established fasting guidelines.

3. The Two-Bag Method for Treatment of Diabetic Ketoacidosis in Adults

A. Comparison of a 'two-bag system' versus conventional treatment protocol ('one-bag system') in the management of DKA

Munir I, et al. BMJ Open Diabetes Res Care. 2017 Aug 11;5(1):e000395.

The ‘two-bag system’ was first described in the early 1990s in pediatric patients. As opposed to the conventional protocol (one-bag system), the two-bag system uses two bags of fluids with identical electrolyte content but different dextrose concentrations, 0% and 10%.20 21 The two bags are connected in a ‘Y’ fashion and by adjusting the infusion rates from each bag, the concentration of dextrose can be customized to prevent unpredictable excursions in blood glucose. The two-bag system has been more commonly used and exclusively studied in the pediatric population and has been found to be cost effective.21 22 It has also been shown to result in more rapid improvement in bicarbonate and ketone correction and a trend toward faster improvement of hyperglycemia in DKA.22 In one study, the two-bag system was well received by nursing and house staff because it was less labor intensive than the traditional one-bag system.23

We compared the conventional 'one-bag protocol' of management of diabetic ketoacidosis (DKA) with the 'two-bag protocol' which utilizes two bags of fluids, one containing saline and supplemental electrolytes and the other containing the same solution with the addition of 10% dextrose.

A retrospective chart review and analysis was done on adult patients admitted for DKA to the Riverside University Health System Medical Center from 2008 to 2015. There were 249 cases of DKA managed by the one-bag system and 134 cases managed by the two-bag system.

The baseline patient characteristics were similar in both groups. The anion gap closed in 13.56 hours in the one-bag group versus 10.94 hours in the two-bag group (p value less than 0.0002). None of the individual factors significantly influenced the anion gap closure time; only the two-bag system favored earlier closure of the anion gap. Plasma glucose levels improved to less than 250 mg/dL earlier with two-bag protocol (9.14 vs 7.82 hours, p=0.0241). The incidence of hypoglycemic events was significantly less frequent with the two-bag protocol compared with the standard one-bag system (1.49% vs 8.43%, p=0.0064). Neither the time to improve serum HCO3 level over 18 mg/dL nor the hospital length of stay differed between the two groups.

Our study indicates that the two-bag protocol closes the anion gap earlier than the one-bag protocol in adult patients with DKA. Blood glucose levels improved faster with the two-bag protocol compared with the one-bag protocol with fewer associated episodes of hypoglycemia. Prospective studies are needed to evaluate the clinical significance of these findings.

B. The Two-Bag Method for Treatment of DKA in Adults.

Haas NL, et al. J Emerg Med. 2018;54(5):593–599.

The "two-bag method" of management of diabetic ketoacidosis (DKA) allows for titration of dextrose delivery by adjusting the infusions of two i.v. fluid bags of varying dextrose concentrations while keeping fluid, electrolyte, and insulin infusion rates constant.

We aimed to evaluate the feasibility and potential benefits of this strategy in adult emergency department (ED) patients with DKA.

This is a before-and-after comparison of a protocol using the two-bag method operationalized in our adult ED in 2015. A retrospective electronic medical record search identified adult ED patients presenting with DKA from January 1, 2013 to June 30, 2016. Clinical and laboratory data, timing of medical therapies, and safety outcomes were collected and analyzed.

Sixty-eight patients managed with the two-bag method (2B) and 107 patients managed with the one-bag method (1B) were identified. The 2B and 1B groups were similar in demographics and baseline metabolic derangements, though significantly more patients in the 2B group received care in a hybrid ED and intensive care unit setting (94.1% vs. 51.4%; p less than 0.01). 2B patients experienced a shorter interval to first serum bicarbonate ≥ 18 mEq/L (13.4 vs. 20.0 h; p less than 0.05), shorter duration of insulin infusion (14.1 vs. 21.8 h; p less than 0.05), and fewer fluid bags were charged to the patient (5.2 vs. 29.7; p less than 0.01). Frequency of any measured hypoglycemia or hypokalemia trended in favor of the 2B group (2.9% vs. 10.3%; p = 0.07; 16.2% vs. 27.1%; p = 0.09; respectively), though did not reach significance.

The 2B method appears feasible for management of adult ED patients with DKA, and use was associated with earlier correction of acidosis, earlier discontinuation of insulin infusion, and fewer i.v. fluid bags charged than traditional 1B methods, while no safety concerns were observed.

4. Mortality Risk Seen from Liberal Oxygen Delivery in MI, Stroke, Other Acute Illnesses

Steve Stiles. Medscape Medical News. May 04, 2018

Short- and long-term mortality goes up after liberal use of supplemental oxygen, compared with a more conservative oxygen delivery approach, in patients with any of a range of acute illnesses, a meta-analysis of randomized trials shows.

The analysis, based on patient-level data from 25 trials, also saw the mortality risk from liberal oxygen as dose-dependent, in that in-hospital and long-term mortality rates climbed with oxygen saturations rising above the threshold of 94% to 96%.

No apparent gains were associated with the liberal approach; the two groups didn't differ in prevalence of hospital-acquired pneumonia, hospital length of stay, or subsequent patient disability.

The findings are "distinct" from "the current notion that at worst, liberal oxygen is not beneficial for acute illnesses," note the authors, led by Derek K. Chu, MD, and Lisa H.-Y. Kim, MD, both from McMaster University, Hamilton, Ontario, Canada.

The current analysis, she said, shows about a 20% increase in hospital mortality when oxygen is given to nonhypoxic critically ill patients, "which is quite significant considering how many patients get exposed to supplemental oxygen in the hospital setting."

Across the studies, she said, there was one death for about every 71 patients given liberal oxygen, a number needed to harm that rose to about 100 in the studies limited to patients with acute coronary syndromes.

"Oxygen shouldn't be treated as a harmless intervention," Kim said. "Now that we have high-quality data that too much oxygen is harmful, we should be really cautious in administering supplemental oxygen. We should really be, frankly, treating it as any prescribed drug, recognizing that it has both benefits and adverse effects."

Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis

Chu DK. Et al. Lancet 2018 Apr 28 [Epub ahead of print]

Supplemental oxygen is often administered liberally to acutely ill adults, but the credibility of the evidence for this practice is unclear. We systematically reviewed the efficacy and safety of liberal versus conservative oxygen therapy in acutely ill adults.

In the Improving Oxygen Therapy in Acute-illness (IOTA) systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, HealthSTAR, LILACS, PapersFirst, and the WHO International Clinical Trials Registry from inception to Oct 25, 2017, for randomised controlled trials comparing liberal and conservative oxygen therapy in acutely ill adults (aged ≥18 years). Studies limited to patients with chronic respiratory diseases or psychiatric disease, patients on extracorporeal life support, or patients treated with hyperbaric oxygen therapy or elective surgery were excluded. We screened studies and extracted summary estimates independently and in duplicate. We also extracted individual patient-level data from survival curves. The main outcomes were mortality (in-hospital, at 30 days, and at longest follow-up) and morbidity (disability at longest follow-up, risk of hospital-acquired pneumonia, any hospital-acquired infection, and length of hospital stay) assessed by random-effects meta-analyses. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study is registered with PROSPERO, number CRD42017065697.

25 randomised controlled trials enrolled 16 037 patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery. Compared with a conservative oxygen strategy, a liberal oxygen strategy (median baseline saturation of peripheral oxygen [SpO2] across trials, 96% [range 94–99%, IQR 96–98]) increased mortality in-hospital (relative risk [RR] 1·21, 95% CI 1·03–1·43, I2=0%, high quality), at 30 days (RR 1·14, 95% CI 1·01–1·29, I2=0%, high quality), and at longest follow-up (RR 1·10, 95% CI 1·00–1·20, I2=0%, high quality). Morbidity outcomes were similar between groups. Findings were robust to trial sequential, subgroup, and sensitivity analyses.

In acutely ill adults, high-quality evidence shows that liberal oxygen therapy increases mortality without improving other patient-important outcomes. Supplemental oxygen might become unfavourable above an SpO2 range of 94–96%. These results support the conservative administration of oxygen therapy.

5. The Surviving Sepsis Campaign Bundle: 2018 update.

Levy MM, et al. Intensive Care Med. 2018 Apr 19 [Epub ahead of print].

The “sepsis bundle” has been central to the implementation of the Surviving Sepsis Campaign (SSC) from the first publication of its evidence-based guidelines in 2004 through subsequent editions [1, 2, 3, 4, 5, 6]. Developed separately from the guidelines publication by the SSC, the bundles have been the cornerstone of sepsis quality improvement since 2005 [7, 8, 9, 10, 11]. As noted when they were introduced, the bundle elements were designed to be updated as indicated by new evidence and have evolved accordingly. In response to the publication of “Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016” [12, 13], a revised “hour-1 bundle” has been developed and is presented below (Fig. 1).

Fig. 1. Hour-1 Surviving Sepsis Campaign Bundle of Care

The compelling nature of the evidence in the literature, which has demonstrated an association between compliance with bundles and improved survival in patients with sepsis and septic shock, led to the adoption of the SSC measures by the National Quality Forum (NQF) and subsequently both by the New York State (NYS) Department of Health [14] and the Centers for Medicare and Medicaid Services (CMS) [15] in the USA for mandated public reporting. The important relationship between the bundles and survival was confirmed in a publication from this NYS initiative [16].

Paramount in the management of patients with sepsis is the concept that sepsis is a medical emergency. As with polytrauma, acute myocardial infarction, and stroke, early identification and appropriate immediate management in the initial hours after development of sepsis improves outcomes…

See the link above for the full-text (free).

6. A Systematic Review and Meta-Analysis of the Management and Outcomes of Isolated Skull Fractures in Children

Bressen S, et al. PECARN. Ann Emerg Med. 2018;71(6):714–724.e2.

STUDY OBJECTIVE: Most studies of children with isolated skull fractures have been relatively small, and rare adverse outcomes may have been missed. Our aim is to quantify the frequency of short-term adverse outcomes of children with isolated skull fractures.

METHODS: PubMed, EMBASE, the Cochrane Library, Scopus, Web of Science, and gray literature were systematically searched to identify studies reporting on short-term adverse outcomes of children aged 18 years or younger with linear, nondisplaced, isolated skull fractures (ie, without traumatic intracranial injury on neuroimaging). Two investigators independently reviewed identified articles for inclusion, assessed quality, and extracted relevant data. Our primary outcome was emergency neurosurgery or death. Secondary outcomes were hospitalization and new intracranial hemorrhage on repeated neuroimaging. Meta-analyses of pooled estimate of each outcome were conducted with random-effects models, and heterogeneity across studies was assessed.

RESULTS: Of the 587 studies screened, the 21 that met our inclusion criteria included 6,646 children with isolated skull fractures. One child needed emergency neurosurgery and no children died (pooled estimate 0.0%; 95% confidence interval [CI] 0.0% to 0.0%; I2=0%). Of the 6,280 children with known emergency department disposition, 4,914 (83%; 95% CI 71% to 92%; I2=99%) were hospitalized. Of the 569 children who underwent repeated neuroimaging, 6 had new evidence of intracranial hemorrhage (0.0%; 95% CI 0.0% to 9.0%; I2=77%); none required operative intervention.

CONCLUSION: Children with isolated skull fractures were at extremely low risk for emergency neurosurgery or death, but were frequently hospitalized. Clinically stable children with an isolated skull fracture may be considered for outpatient management in the absence of other clinical concerns.

7. Clinical Aspects of Anticoagulation

A. Safety of Lumbar Puncture Performed on Dual Antiplatelet Therapy.

Carabenciov ID, et al. Mayo Clin Proc. 2018.

Practice guidelines generally recommend delaying lumbar puncture (LP) in patients on dual antiplatelet therapy, with these recommendations often citing an increased risk of hemorrhagic complications, specifically the development of epidural hematomas. However, no data exist about the risks of performing an LP in the setting of dual antiplatelet therapy and conclusions are often based on data from spinal anesthesia literature. We reviewed the medical records of 100 patients who underwent LP while taking dual antiplatelet therapy. We recorded the number of traumatic and bloody cerebrospinal fluid results as well as the presence of any complications occurring within 3 months of the procedure. Complications requiring imaging or hospitalization were considered serious.

The most common complication was back pain, which was reported by 2 patients, only 1 of which was ultimately found to be attributable to the procedure. No serious complications occurred. Cerebrospinal fluid analysis was consistent with a traumatic LP, defined as having at least 100 red blood cells per microliter, in 8% of cases. Bloody LP, defined as having 1000 red blood cells per microliter, occurred in 4% of cases. The percentage of traumatic or bloody LPs was within the range reported previously for LPs performed in any setting. Although this is a small study and additional review is necessary, performing LPs in the setting of dual antiplatelet therapy may not pose an increased risk of serious complications.

B. Management of Bleeding in Patients Taking Oral Anticoagulants: ACC Guidelines

Anderson I, et al. JAMA. 2018;319(19):2032-2033.

Summary of the Clinical Problem
More than 6 million people in the United States take OACs.1 The most common indications for OACs are atrial fibrillation and treatment or prevention of venothromboembolism.1 Hemorrhage and its related morbidity and mortality are the primary risks associated with these agents.2 A meta-analysis of 13 randomized clinical trials involving 102 707 adults showed major bleeding case-fatality rates of 7.57% with DOACs and 11.05% with warfarin.2 With the approval of 4 DOACs since 2010, management of OAC-associated bleeding has become more complex.

Guideline title: American College of Cardiology Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants

Developer: ACC Foundation

Release date: December 1, 2017

Target population: Patients treated with direct oral anticoagulants (DOACs) or warfarin for any indication who have acute bleeding

Major recommendations: For patients treated with an oral anticoagulant (OAC) who experience either life-threatening bleeding or major bleeding at a critical site, management should include at least temporarily discontinuing the OAC, local therapy, supportive measures, and, when appropriate, administering a reversal agent.

•For warfarin, 5 to 10 mg of intravenous vitamin K and intravenous 4-factor prothrombin complex concentrate (4F-PCC)

•For dabigatran, intravenous idarucizumab or intravenous 4F-PCC/activated prothrombin complex concentrate (aPCC)

•For apixaban, edoxaban, and rivaroxaban, intravenous 4F-PCC or intravenous aPCC

Laboratory testing may be useful to determine reversal strategy for life-threatening bleeding or bleeding at a critical site or prior to urgent unplanned procedures.

For dabigatran
•Normal levels of any of the following probably indicate that drug levels are insignificant: dilute thrombin time (TT); ecarin clotting time (ECT); ecarin chromogenic assay (ECA).
•Normal activated partial thromboplastin time (aPTT) usually indicates that drug levels are insignificant. Prolonged aPTT suggests that a patient has a significant drug level (either therapeutic or supratherapeutic).

For apixaban, edoxaban, and rivaroxaban
•Negative anti–factor Xa assay activity usually indicates that drug levels are insignificant.
•Normal prothrombin time/aPTT does not exclude a significant drug level. Prolonged prothrombin time suggests that a patient has a clinically significant drug level (either therapeutic or supratherapeutic).

C. FDA Approves First Factor Xa Inhibitor Antidote, Andexxa

Patrice Wendling. Medscape. May 04, 2018

The US Food and Drug Administration (FDA) has approved Andexxa (coagulation factor Xa [recombinant] inactivated-zhzo) to reverse the anticoagulation effects of factor Xa inhibitors when needed due to life-threatening or uncontrolled bleeding, Portola Pharmaceuticals has announced.

An estimated 4 million people are taking factor Xa inhibitors, such as rivaroxaban (Xarelto, Bayer/Janssen Pharmaceuticals) and apixaban (Eliquis, Bristol-Myers Squibb), but until now, there has been no approved reversal agent.

Last month, the FDA gave full approval to idarucizumab (Praxbind, Boehringer Ingelheim) to reverse the anticoagulant effect of dabigatran (Pradaxa, Boehringer Ingelheim), a direct thrombin inhibitor, in the event of urgent surgery or life-threatening or uncontrolled bleeding.

In the United States alone, there were approximately 117,000 hospital admissions attributable to factor Xa inhibitor-related bleeding and nearly 2000 bleeding related deaths per month, according to the company's news release, posted May 3.

"The expansion of available reversal agents for people prescribed newer oral anticoagulant therapies is crucial," Randy Fenninger, chief executive officer of the National Blood Clot Alliance, said in the release. "The availability now of a reversal agent specific to rivaroxaban and apixaban expands choice and enables patients and providers to consider these treatment options with greater confidence."

Andexxa was approved under the FDA's accelerated approval pathway based on effects in healthy volunteers, and continued approval may be contingent on postmarketing studies to demonstrate an improvement in hemostasis in patients. A clinical trial comparing this agent or usual care is scheduled to start in 2019 and to be reported in 2023.

Andexxa was approved with a boxed warning for thromboembolic risks, ischemic risks, cardiac arrest, and sudden death. Treatment with the agent has been associated with serious and life-threatening adverse events, including arterial and venous thromboembolic events, cardiac arrest, sudden deaths, and ischemic events, such as myocardial infarction and ischemic stroke.

The most common adverse reactions in at least 5% of patients receiving Andexxa were urinary tract infections and pneumonia.

8. ED Intubation Success with Succinylcholine Versus Rocuronium: A National Emergency Airway Registry Study

April MD, et al. Ann Emerg Med 2018 May 7 [Epub ahead of print]

Study objective
Although both succinylcholine and rocuronium are used to facilitate emergency department (ED) rapid sequence intubation, the difference in intubation success rate between them is unknown. We compare first-pass intubation success between ED rapid sequence intubation facilitated by succinylcholine versus rocuronium.

We analyzed prospectively collected data from the National Emergency Airway Registry, a multicenter registry collecting data on all intubations performed in 22 EDs. We included intubations of patients older than 14 years who received succinylcholine or rocuronium during 2016. We compared the first-pass intubation success between patients receiving succinylcholine and those receiving rocuronium. We also compared the incidence of adverse events (cardiac arrest, dental trauma, direct airway injury, dysrhythmias, epistaxis, esophageal intubation, hypotension, hypoxia, iatrogenic bleeding, laryngoscope failure, laryngospasm, lip laceration, main-stem bronchus intubation, malignant hyperthermia, medication error, pharyngeal laceration, pneumothorax, endotracheal tube cuff failure, and vomiting). We conducted subgroup analyses stratified by paralytic weight-based dose.

There were 2,275 rapid sequence intubations facilitated by succinylcholine and 1,800 by rocuronium. Patients receiving succinylcholine were younger and more likely to undergo intubation with video laryngoscopy and by more experienced providers. First-pass intubation success rate was 87.0% with succinylcholine versus 87.5% with rocuronium (adjusted odds ratio 0.9; 95% confidence interval 0.6 to 1.3). The incidence of any adverse event was also comparable between these agents: 14.7% for succinylcholine versus 14.8% for rocuronium (adjusted odds ratio 1.1; 95% confidence interval 0.9 to 1.3). We observed similar results when they were stratified by paralytic weight-based dose.

In this large observational series, we did not detect an association between paralytic choice and first-pass rapid sequence intubation success or peri-intubation adverse events.

9. Ultrasound Corner

A. Introducing the CASA Exam: A New Protocol to Guide Point-Of-Care Ultrasound in Cardiac Arrest

Gardner K, et al. ACEP Now, May 1, 2018

The CASA exam is a three-step protocol that evaluates for:

Pericardial effusion
Right heart strain indicative of a pulmonary embolus
Cardiac activity

All three steps can be rapidly performed with a cardiac (phased array) transducer.

Tamponade and pulmonary embolism (PE) are potentially reversible causes if identified quickly, and the presence or absence of cardiac activity provides information regarding prognosis.5 This step-wise approach allows for the integration of POCUS in the resuscitation of the critically ill patient while maintaining the evidence-based principles of continuous, high-quality CPR. If and when return of spontaneous circulation (ROSC) is achieved, a more comprehensive ultrasound assessment should be performed.

B. Lung ultrasound better than CXR for diagnosis of pediatric pneumonia: A meta‐analysis

Balk DS, et al. Pediatr Pulmonol 2018 April 26

OBJECTIVE: Although a clinical diagnosis, the standard initial imaging modality for patients with concern for pediatric community acquired pneumonia (pCAP) is a chest x-ray (CXR), which has a relatively high false negative rate, exposes patients to ionizing radiation, and may not be available in resource limited settings. The primary objective of this meta-analysis is to evaluate the accuracy of lung ultrasound (LUS) compared to CXR for the diagnosis of pCAP.

METHODS: Data were collected via a systematic review of PubMed, EMBASE, and Web of Science with dates up to August 2017. Keywords and search terms were generated for pneumonia, lung ultrasound, and pediatric population. Two independent investigators screened abstracts for inclusion. PRISMA was used for selecting appropriate studies. QUADAS was applied to these studies to assess quality for inclusion into the meta-analysis. We collected data from included studies and calculated sensitivity, specificity, positive predictive value, and negative predictive values of CXR and LUS for the diagnosis of pCAP.

RESULTS: Twelve studies including 1510 patients were selected for data extraction. LUS had a sensitivity of 95.5% (93.6-97.1) and specificity of 95.3% (91.1-98.3). CXR had a sensitivity of 86.8% (83.3-90.0) and specificity of 98.2% (95.7-99.6). Variations between the studies included ultrasound findings diagnostic of pneumonia, study setting (inpatient vs emergency department) and inclusion of CXR in the reference standard for pneumonia.

CONCLUSIONS: In our meta-analysis, lung ultrasound had significantly better sensitivity with similar specificity when compared to chest x-ray for the diagnosis of pediatric community acquired pneumonia.

C. Bedside ultrasound to detect CVC misplacement and associated iatrogenic complications: a systematic review and meta-analysis.

Smit JM, et al. Crit Care. 2018 Mar 13;22(1):65.

BACKGROUND: Insertion of a central venous catheter (CVC) is common practice in critical care medicine. Complications arising from CVC placement are mostly due to a pneumothorax or malposition. Correct position is currently confirmed by chest x-ray, while ultrasonography might be a more suitable option. We performed a meta-analysis of the available studies with the primary aim of synthesizing information regarding detection of CVC-related complications and misplacement using ultrasound (US).

METHODS: This is a systematic review and meta-analysis registered at PROSPERO (CRD42016050698). PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched. Articles which reported the diagnostic accuracy of US in detecting the position of CVCs and the mechanical complications associated with insertion were included. Primary outcomes were specificity and sensitivity of US. Secondary outcomes included prevalence of malposition and pneumothorax, feasibility of US examination, and time to perform and interpret both US and chest x-ray. A qualitative assessment was performed using the QUADAS-2 tool.

RESULTS: We included 25 studies with a total of 2548 patients and 2602 CVC placements. Analysis yielded a pooled specificity of 98.9 (95% confidence interval (CI): 97.8-99.5) and sensitivity of 68.2 (95% CI: 54.4-79.4). US examination was feasible in 96.8% of the cases. The prevalence of CVC malposition and pneumothorax was 6.8% and 1.1%, respectively. The mean time for US performance was 2.83 min (95% CI: 2.77-2.89 min) min, while chest x-ray performance took 34.7 min (95% CI: 32.6-36.7 min). US was feasible in 97%. Further analyses were performed by defining subgroups based on the different utilized US protocols and on intra-atrial and extra-atrial misplacement. Vascular US combined with transthoracic echocardiography was most accurate.

CONCLUSIONS: US is an accurate and feasible diagnostic modality to detect CVC malposition and iatrogenic pneumothorax. Advantages of US over chest x-ray are that it can be performed faster and does not subject patients to radiation. Vascular US combined with transthoracic echocardiography is advised. However, the results need to be interpreted with caution since included studies were often underpowered and had methodological limitations. A large multicenter study investigating optimal US protocol, among other things, is needed.

D. Prehospital Ultrasound: Ready for Prime Time?

Michael T. Hilton, MD, MPH. Medscape. May 03, 2018

Commonly used by physicians in emergency departments and intensive care units as a physical examination adjunct for rapid bedside diagnostic testing and for procedural guidance,[1] portable ultrasound has been making its way into the hands of emergency medical technicians (EMTs) and paramedics on ambulances and helicopters in the United States and abroad.[2]

In North America, 4% of emergency medical services (EMS) systems use ultrasound and 20% are considering implementing ultrasound within their systems.[3] The most common uses for prehospital ultrasound are the Focused Assessment with Sonography for Trauma (FAST) and assessment of pulseless electrical activity arrest.[3] With education and training, paramedics and EMTs can obtain images of sufficient quality.[4,5] However, whether this improves outcomes for patients is unclear.

There is no standardized training for paramedics or EMTs in the use of ultrasound, leading to great variability in curricula published in the literature. For specific ultrasound skills, such as image acquisition for abdominal trauma (FAST), a 1-day training course may be sufficient.[6] A 6-hour FAST training program has been published.[7] Alternatively, a comprehensive multimodal 2-month training course has also been proposed to train paramedics to perform the Extended Focused Assessment with Sonography for Trauma (eFAST).[8] For identification of pericardial effusion, pneuomothorax, and cardiac standstill, a 1-hour lecture has been trialed among EMT and paramedic students, and a 2-hour program has also been used to train paramedics for these indications.[9,10] A systematic review of training courses for paramedic prehospital ultrasound has shown that FAST ultrasound examination can be taught in 6-8 hours and that pleural ultrasound can be taught in 25 minutes.[11] For the other uses of ultrasound in the field, training programs have not been published in the literature.

The remainder of the essay (registration required):

10. Images in Clinical Practice

A Woman With Stridor and Respiratory Failure

A Woman With a Click in Her Throat

Young Woman With a Sore Throat and Neck Mass

Young Man With Wrist Pain

Adult Male With Scrotal Swelling and Pain

Woman With Hand Pain and Swelling

Adolescent Female With Right Ear Redness

Infant With Episodes of Bilious Vomiting

Young Woman With Postpartum Chest and Abdominal Pain

Colon Cutoff Sign

Orbital Apex Syndrome

Aspiration of a Chicken Bone

Relapsing Polychondritis

Trypanosoma cruzi Reactivation in the Brain

Xanthoma Striatum Palmare

Raindrop Skull

Tuberculous Pericarditis

11. Helpful Reviews from Ann Emerg Med

A. Does Bed Rest or Fluid Supplementation Prevent Post–Dural Puncture Headache?

Take-Home Message
Neither bed rest nor fluid supplementation decreases the incidence of headache after dural puncture.

B. Managing Peripheral Facial Palsy

Patients with acute-onset peripheral facial palsy commonly present to the ED for evaluation and treatment. ED clinicians should promptly initiate appropriate therapy to improve long-term recovery. For patients with high risk for Lyme disease facial palsy, we recommend empiric antibiotics while awaiting Lyme disease test results. All other patients should be treated with corticosteroids, and those with severe facial palsy should also be treated with antivirals.

C. Diagnosing Patients With Acute-Onset Persistent Dizziness

Three percent of emergency department (ED) patients present with dizziness, vertigo, lightheadedness, or imbalance.1 These words are not diagnostically meaningful.2 Rather, it is the timing and the factors that trigger the dizziness that best inform the differential diagnosis.3 Asking a patient, “What do you mean by ‘dizzy’?” is less important than defining the rapidity of onset, the context, presence of associated symptoms, the intermittent or persistent nature of the dizziness, and triggers of intermittent symptoms.2, 4, 5, 6

Approximately 50% of dizzy patients have general medical conditions.1 Associated symptoms (eg, gastrointestinal bleeding) or context (eg, new antihypertensive medications) usually suggest these diagnoses. Some patients endorse brief episodes of dizziness triggered by head or body movement, suggesting benign paroxysmal positional vertigo or orthostatic hypotension. Other patients have short spontaneous episodes of dizziness that are not triggered by anything consistent with posterior circulation transient ischemic attacks or vestibular migraine.

This article focuses on a different group of patients: those with the acute onset of severe persistent and continuous dizziness or vertigo often associated with nausea or vomiting and postural instability that remains present in the ED without an obvious medical cause. Classically, nystagmus is included as a component of the acute vestibular syndrome.7 However, not all patients with acute-onset severe persistent dizziness have nystagmus.

To be clear about this distinction, I use the terms “acute vestibular syndrome with nystagmus” and “acute vestibular syndrome without nystagmus.” The distinction is important because the diagnostic approach differs somewhat between these 2 groups. The word vestibular refers to the symptoms, not to any anatomic localization. The major differential diagnosis is vestibular neuritis versus posterior circulation stroke. This article focuses on distinguishing these 2 entities in the ED and uses the term dizziness in the general sense…

E. How Reliable Are Signs and Symptoms for Diagnosing Pneumonia in Pediatric Patients?

Take-Home Message
In children younger than 5 years, no single historical features or findings can reliably differentiate pneumonia from other pediatric respiratory illnesses.

Full-text (free):

12. Impact of Emergency Physician–Provided Patient Education About Alternative Care Venues

Patel PB, et al. Am J Manag Care. 2018;24(5):225-231.

Objectives: Interventions that focus on educating patients appear to be the most effective in directing healthcare utilization to more appropriate venues. We sought to evaluate the effects of mailed information and a brief scripted educational phone call from an emergency physician (EP) on subsequent emergency department (ED) utilization by low-risk adults with a recent treat-and-release ED visit.

Study Design: Patients were randomized into 3 groups for post-ED follow-up: EP phone call with mailed information, mailed information only, and no educational intervention. Each intervention group was compared with a set of matched controls.

Methods: We undertook this study in 6 EDs within an integrated healthcare delivery system. Overall, 9093 patients were identified; the final groups were the phone group (n = 609), mail group (n = 771), and matched control groups for each (n = 1827 and n = 1542, respectively). Analysis was stratified by age (less than 65 and 65 years or older). Patients were educated about available venues of care delivery for their future medical needs. The primary outcome was the rate of 6-month ED utilization after the intervention compared with the 6-month utilization rate preceding the intervention.

Results: Compared with matched controls, subsequent ED utilization decreased by 22% for patients 65 years or older in the phone group (P = .04) and by 27% for patients younger than 65 years in the mail group (P = .03).

Conclusions: ED utilization subsequent to a low-acuity ED visit decreased after a brief post-ED education intervention by an EP explaining alternative venues of care for future medical needs. Response to the method of communication (phone vs mail) varied significantly by patient age.

Editorial: Delivery of acute unscheduled healthcare: who should judge whether a visit is appropriate (or not)?

Press release: Can Patients Be Taught to Avoid Unnecessary Trips to the ER? A Study in AJMC® Suggests Some Can

13. Aromatherapy Versus Oral Ondansetron for Antiemetic Therapy Among Adult ED Patients: A RCT

April MD, et al. Ann Emerg Med 2018 Feb 17 [Epub ahead of print]

Study Objective
We compare aromatherapy with inhaled isopropyl alcohol versus oral ondansetron for treating nausea among emergency department (ED) patients not requiring immediate intravenous access.

In a randomized, blinded, placebo-controlled trial, we enrolled a convenience sample of adults presenting to an urban tertiary care ED with chief complaints including nausea or vomiting. We randomized subjects to 1 of 3 arms: inhaled isopropyl alcohol and 4 mg oral ondansetron, inhaled isopropyl alcohol and oral placebo, and inhaled saline solution placebo and 4 mg oral ondansetron. The primary outcome was mean nausea reduction measured by a 0- to 100-mm visual analog scale from enrollment to 30 minutes postintervention. Secondary outcomes included receipt of rescue antiemetic medications and adverse events.

We enrolled 122 subjects, of whom 120 (98.3%) completed the study. Of randomized subjects, 40 received inhaled isopropyl alcohol and oral ondansetron, 41 received inhaled isopropyl alcohol and oral placebo, and 41 received inhaled saline solution placebo and oral ondansetron. The mean decrease in nausea visual analog scale score in each arm was 30 mm (95% confidence interval [CI] 22 to 37 mm), 32 mm (95% CI 25 to 39 mm), and 9 mm (95% CI 5 to 14 mm), respectively. The proportions of subjects who received rescue antiemetic therapy in each arm were 27.5% (95% CI 14.6% to 43.9%), 25.0% (95% CI 12.7% to 41.2%), and 45.0% (95% CI 29.3% to 61.5%), respectively. There were no adverse events.

Among ED patients with acute nausea and not requiring immediate intravenous access, aromatherapy with or without oral ondansetron provides greater nausea relief than oral ondansetron alone.

14. Towards a Better Understanding of Our Patients

A. ‘How Were You Hoping I Could Help You Today?’

Walker G. Emerg Med News. 2018;40(5):19

It is obvious why many of our patients come to the ED: Something happened to them (they were hit by a car) or they developed some acute symptom (six hours of right lower abdominal pain), and they're seeking answers—diagnosis, treatment, or both. Because we emergency physicians know our resources and our scope, it's easy for us to understand their motivations, and we work them up and treat them as needed.

But it is not readily obvious to us why some of our patients presented: “Six months of abdominal pain,” “URI symptoms; has two siblings with the same,” “rash times seven years.” These patients always confuse and bewilder me. More often than not, they seem just as dissatisfied after the ED visit as they did before. I've tried all kinds of questions to sort them out:

In residency, I would sometimes smarmily ask patients, “What is your emergency today?” It felt vindicating, especially when the patient's chief complaint was “sore throat for 20 minutes,” and she's in the exam room eating a toasted Quizno's sub.

I've also tried asking people, “Oh, what has your primary care physician said about this?” (when I know they have a primary care physician). They usually look back at me perplexed, confused by the suggestion that their primary care physician could handle most of these issues.
And adults, I find, don't like the questions that typically work in pediatrics: “What's your biggest concern today?” or “What are you worried about?” I imagine that these patients don't respond well to “concern” or “worry” because they're not really worried about the rash on their side; they just want it gone.

As I matured, I tried asking people, “What made you come in today if it's been going on for three years? Did it get worse? Did something change? Did you have a new symptom? Or were you just tired of it?” The vast majority of patients typically shrug and choose the last answer, almost to the point of suggesting that it was pure fate, and they had no free will or choice in deciding to register in the ED.

None of these questions really ever seemed to get the answers I was seeking: What did the patient expect from me,what did the patient want from me (they're not always the same thing), and what would it take to satisfy him? Then I came across the phrase that seemed to sum up all of this: How were you hoping I could help you today?

A Dose of Reassurance
This is best used with patients who have chronic complaints, but it works quite well with the patients who have already correctly self-diagnosed: “I think I have a cold;” “I think I sprained my ankle;” “I scraped my knee;” “I want an abortion.” The magic of this phrase is that it also engages the patient, revealing any hidden anxieties he may have and letting you reassure him.

It also lets you instantly know how realistic or delusional they are about what will or won't or can or can't happen in the emergency department. You immediately know, “OK, this is going to be an easy one,” or “Oof, this is going to take some teamwork to set expectations and come up with a plan, and even after that, it may not go smoothly.”

Take any one of the many patients I saw last week with the three to four days of the flu, many of which stated outright, “I think I have the flu.” Ask the magic question, and you'll get a variety of responses, most of which require a variety of solutions. “How were you hoping I could help you today?”

“I've been sick all week, and I have midterms on Monday.” Ta-da, here's your school/work note.

“I'm worried it's not the flu. I take Tylenol, but then my fever comes back.” Ta-da, education about fever and a recommendation to add ibuprofen.

“I've seen my doctor for this twice already this week, and I'm still not feeling better. I only have one kidney, so I'm worried I'm dehydrated.” Shared decision-making about other testing like a chest x-ray and labs (which, of course, turned out totally normal; diagnosis: flu).

“I have a newborn at home, so I'm worried I might give this to him.” Education about hand washing, masks, and lots of new parenting advice, as well as gathering information about the infant's age, taking an infant's temperature, etc. Discussion about risks/benefits of oseltamivir.

You'll notice that only one of these four scenarios required much in the way of medical workup or even medical care; it's much more about targeted education and reassurance (because you've already taken a history, examined the patient, and deemed his condition not to require any testing).

It's far better to spend an extra five minutes with the patient doing a thorough physical exam and answering all of his questions and then being able to discharge him than to order unnecessary testing, come back an hour later, announce, “Good news. The x-ray is normal!” and then have him leave annoyed. Even worse is then having him ask you or the nurse five minutes of additional questions. And the ultimate fail is having the patient re-triage an hour later for the same complaint, already worked up and annoyed for your colleague to see. (That being said, sometimes you don't have five minutes to spare for patients with minor complaints, or tests have already been ordered in triage.)

Give the phrase a try. I promise you at least a patient a day will be easier for you to handle, understand, empathize with, and disposition.

B. Uncertainty Commonly Leads To Repeat ED Visits

New tool may clarify the reasons, point to solutions

Jennifer Thew RN, HealthLeaders Media. April 29, 2018

Until now, the reasons why patients return to the emergency department after an initial visit have been anyone's guess.

"We don't do a good job of predicting which patients will come back to the emergency department, which means we don't have a good understanding of why patients are coming back and how we could be assisting them in having a safer transition home from the first emergency department visit," Kristin Rising, MD, director of acute care transitions and associate professor of emergency medicine at Thomas Jefferson University in Philadelphia, said in a news release.

However, through interview-based studies, Rising identified a common theme among these patients -- uncertainty.

To better understand, document, and create effective solutions to address uncertainty -- whether it be about managing symptoms or a disease process -- Rising and a team of Jefferson researchers developed the Uncertainty Scale.

"As a field, we've had difficulty finding an approach that consistently works to identify and address individual patient needs. The Uncertainty Scale we developed gives us a tool to help do that," Rising said.

Reasons for Uncertainty
The researchers took a patient-centered approach and developed the U-Scale based on direct patient input and listening sessions. The team spent two 6-hour days with two groups, each of about 20 patients, who had recently been patients in the ED. The patients brainstormed the types of uncertainty people have when they experience symptoms that may trigger an ED visit. They then worked with the research team to map the ideas into categories.

Some of the categories were: 
  • Concern over treatment quality, which may lead a patient to return in hopes of a second opinion
  • Concern about lack of a diagnosis, thus leaving a patient with no satisfying explanation for their symptoms
  • Lack of clarity regarding self-management, such that patients are unsure how to deal with symptoms at home
  • Lack of self-efficacy, manifesting as patients not knowing where to go for help for certain symptoms
  • Lack of clarity about the decision to seek care, meaning that patients do not know which symptoms are serious enough to warrant seeing a health professional
  • Psychosocial factors, including worries that getting medical care might interfere with home and work commitments
  • General worries and concerns 

Improve Provider-Patient Conversations
Rising advocates for training healthcare professionals about patient struggles related to uncertainty. She is working to develop a curriculum to teach physician residents to have more effective discharge conversations with patients when testing has not identified a definitive cause of their symptoms.

“As emergency physicians, we focus primarily on acute care, fixing the most immediate life-threatening problems. Facilitating a safe and effective transition home for patients who do not appear to have a life-threatening problem is also a really critical part of our job that is often overlooked,” Rising says.

The research has changed how Rising delivers news to her patients. She realized what she considers good news – that tests are normal and a patient’s symptoms do not appear to be life threatening – could actually be experienced as bad news from the patient perspective. She now takes time to acknowledge and validate potential patient struggles related to ongoing uncertainty.

“If a patient comes in with a problem and I tell him that testing is normal and I haven’t found a cause of his symptoms, it might give momentary relief, but that patient still is no closer to understanding what is causing his distress. It’s not all good news, and we have to acknowledge that we have not improved patients’ sense of uncertainty about their disease with this news,” she says.

The team of researchers plans to continue to refine and validate the U-Scale, and use it to test interventions to alleviate different categories of uncertainty.

15. ALiEM Highlights

A. Ketamine for Severe Ethanol Withdrawal: A New Hope?

By Bryan D Hayes. ALiEM. May 16, 2018

Ethanol withdrawal is a complex disease state. Two of the main players are GABA (an inhibitory neurotransmitter) and glutamate (an excitatory transmitter that can act on NMDA receptors). Chronic ethanol use leads to a down-regulation of GABA receptors and an up-regulation in glutaminergic receptors, such as NMDA. When ethanol is abruptly discontinued, we are left with a largely excitatory state with less ability for GABA-mediated inhibition and more capacity for NMDA/glutamate-mediated excitation. While much of the treatment of severe ethanol withdrawal is focused on GABA, there are agents, such as phenobarbital and propofol, that can suppress the glutaminergic response. Ketamine seems like it would confer benefit as well due to its NMDA antagonist properties. Until now there was only one clinical study using ketamine for severe ethanol withdrawal.1 Now there are two.2

In this post, we will review the body of evidence for ketamine in severe ethanol withdrawal and explain its potential application to clinical practice…

B. A Can’t Miss ED Diagnosis: Euglycemic DKA

Theresa Kim, MD. March 19th, 2018

A middle-aged man with a history of diabetes and hypertension presents with nausea, vomiting, and shortness of breath. His laboratory testing is remarkable for a leukocytosis, ketonemia, and an anion gap acidosis (pH of 7.13). The EM resident caring for this patient is surprised to find that the blood glucose is 121 mg/dL.

Which home medication is likely responsible for this presentation? 
  • Metformin
  • Glipizide
  • Liraglutide
  • Canagliflozin 

16. Only 5.5 Percent of Emergency Visits Are Nonurgent and Wait Times Continue to Improve, CDC Says

WASHINGTON, April 23, 2018 /PRNewswire-USNewswire/ -- New data from the Centers for Disease Control and Prevention (CDC) show that 136.9 million people visited the emergency department in 2015 and only 5.5 percent of these visits were considered "nonurgent," according to the latest CDC National Hospital Ambulatory Medical Care (NHAMC) survey.

"Emergency care is a unique success story," said Paul Kivela, MD, MBA, FACEP, president of ACEP. "No other medical specialty is the safety net for millions of patients with such a broad range of symptoms and conditions. The nation's emergency physicians care for any patient, any time, regardless of ability to pay — and we play an increasingly integral role in our health system."

Wait times continued to improve, according to the report. Typically, about 35 percent of patients waited less than 15 minutes to see a provider and 68 percent were seen in less than one hour. The median wait time to see a physician or advanced practice provider is 18 minutes, and the median time spent in the emergency department was around 180 minutes, which includes time with the physician and other members of the care team and other clinical services.

Injuries, stomach pain and chest pain top the list of conditions bringing patients to the emergency department. Various injuries accounted for about 28 percent of visits. Illness accounted for about 65 percent of visits, and mental health related conditions or other reasons made up the remaining 7 percent or so…

17. Opioid Corner

A. ED Makes Only Small Contribution to the Prescription Opioid Epidemic.

Axeen S, Seabury SA, Menchine M. Ann Emerg Med. 2018;71(6):659–667.e3.

Study objective
We characterize the relative contribution of emergency departments (EDs) to national opioid prescribing, estimate trends in opioid prescribing by site of care (ED, office-based, and inpatient), and examine whether higher-risk opioid users receive a disproportionate quantity of their opioids from ED settings.

This was a retrospective analysis of the nationally representative Medical Expenditure Panel Survey from 1996 to 2012. Individuals younger than 18 years and with malignancy diagnoses were excluded. All prescriptions were standardized through conversion to milligrams of morphine equivalents. Reported estimates are adjusted with multivariable regression analysis.

From 1996 to 2012, 47,081 patient-years (survey-weighted population of 483,654,902 patient-years) surveyed by the Medical Expenditure Panel Survey received at least 1 opioid prescription. During the same period, we observed a 471% increase in the total quantity of opioids (measured by total milligrams of morphine equivalents) prescribed in the United States. The proportion of opioids from office-based prescriptions was high and increased throughout the study period (71% of the total in 1996 to 83% in 2012). The amount of opioids originating from the ED was modest and declined throughout the study period (7.4% in 1996 versus 4.4% in 2012). For people in the top 5% of opioid consumption, ED prescriptions accounted for only 2.4% of their total milligrams of morphine equivalents compared with 87.8% from office visits.

Between 1996 and 2012, opioid prescribing for noncancer patients in the United States significantly increased. The majority of this growth was attributable to office visits and refills of previously prescribed opioids. The relative contribution of EDs to the prescription opioid problem was modest and declining. Thus, further efforts to reduce the quantity of opioids prescribed may have limited effect in the ED and should focus on office-based settings. EDs could instead focus on developing and disseminating tools to help providers identify high-risk individuals and refer them to treatment.

B. The Supply of Prescription Opioids: Contributions of Episodic-Care Prescribers and High-Quantity Prescribers

Schneberk T, Raffetto B, Kim D, Schriger DL. Ann Emerg Med 2018;71(6):668–673.e3.

We determine episodic and high-quantity prescribers' contribution to opioid prescriptions and total morphine milligram equivalents in California, especially among individuals prescribed large amounts of opioids.

This was a cross-sectional descriptive analysis of opioid prescribing patterns during an 8-year period using the de-identified Controlled Substance Utilization Review and Evaluation System (CURES) database, the California subsection of the prescription drug monitoring program. We took a 10% random sample of all patients and stratified them by the amount of prescription opioids obtained during their maximal 90-day period. We identified "episodic prescribers" as those whose prescribing pattern included short-acting opioids on greater than 95% of all prescriptions, fewer than or equal to 31 pills on 95% of all prescriptions, only 1 prescription in the database for greater than 90% of all patients to whom they gave opioids, fewer than 6 prescriptions in the database to greater than 99% of patients given opioids, and fewer than 540 prescriptions per year. We identified top 5% prescribers by their morphine milligram equivalents per day in the database. We examined the relationship between patient opioid prescriptions and provider type, with the primary analysis performed on the patient cohort who received only short-acting opioids in an attempt to avoid guideline-concordant palliative, oncologic, and addiction care, and a secondary analysis performed on all patients.

Among patients with short-acting opioid only, episodic prescribers (14.6% of 173,000 prescribers) wrote at least one prescription to 25% of 2.7 million individuals but were responsible for less than 9% of the 10.5 million opioid prescriptions and less than 3% of the 3.9 billion morphine milligram equivalents in our sample. Among individuals with high morphine milligram equivalents use, episodic prescribers were responsible for 2.8% of prescriptions and 0.6% of total morphine milligram equivalents. Conversely, the top 5% of prescribers prescribed at least 29.8% of prescriptions and 48.8% of total morphine milligram equivalents, with a greater contribution in patients with high morphine milligram equivalents.

Episodic prescribers contribute minimally to total opioid prescriptions, especially among individuals categorized as using high morphine milligram equivalents. Interventions focused on reducing opioid prescriptions in the episodic care setting are unlikely to yield important reductions in the prescription opioid supply; conversely, targeting high-quantity prescribers has the potential to create substantial reductions.

C. Looking Ahead: The Role of Emergency Physicians in the Opioid Epidemic

Lynch MJ, Yealy DM. Ann Emerg Med. 2018:71(6):676-678.

Excerpts from the editorial accompanying the two studies above:

…Despite the common narrative implicating EDs as a high-frequency site instigating or sustaining a cascade of events leading to nonmedical opioid use, addiction, and death, the data by Axeen et al8 and Schneberk et al9 indicate that EDs play a small role in the overall supply of prescription opioids, particularly to individuals at highest risk. These findings are consistent with previously published work. Barnett et al10 found that the rate of 1-year opioid use after opioid-naive patients obtained an initial prescription obtained from an ED was no greater than 1.5%. The authors were not able to distinguish whether successive opioid prescriptions were related to nonmedical use, ongoing pain, or recurrent acutely painful conditions. Their finding of a maximum incidence of 1-year post-ED opioid use of 1.5% contrasts with the 6% of patients prescribed at least 1 day of opioid therapy from any site, as reported by Shah et al.11 Jeffery et al12 found that opioid prescriptions originating from EDs were more likely to be compliant with Centers for Disease Control and Prevention guidelines and significantly less likely to result in long-term use than prescriptions provided to opioid-naive patients in other health care settings.

Despite the small ED role, we believe it is incumbent on all physicians—including ED providers—to critically review analgesic options, both pharmacologic and behavioral, to adequately treat pain and mitigate the very small but present risk of developing an opioid use disorder. The observation that 80% of injection drug users “started” with nonmedical use of prescription opioids14 may mischaracterize addiction as a de novo development resulting from a single, short-term prescription. Such a causal conclusion ignores preexisting risk factors and indicators, including nonopioid substance use and psychological trauma unrecognized by the provider and patient.

Finally, the ED remains ground zero for interfacing with the tragedy of opioid addiction; in our roles as emergency physicians or other care providers, we see the effect of addiction and the death or near-death experience, often in otherwise young and healthy patients. Our ability to recognize and address the addiction, withhold opioids in this select group, and prepare for any re-exposure by teaching and easing delivery of reversal therapy for home use (naloxone) is key and likely more influential than any regulation limiting ED prescribing to “X tablets or days” for all. Starting acute detoxification, advocating and working to create accessible addiction treatment after an ED visit, and other steps are needed and sorely missing in most settings; we should lead these efforts to create and fund solutions if we seek to stem the opioid overdose tide. Advocating for these steps—harder and more expensive steps—is more likely to alter the opioid epidemic than ED prescribing regulations, and recognizing patients who achieve these interventions is more worthy than “going opioid free.”

Across the United States, EDs care for many patients with acutely painful conditions, making these sites attractive targets for policy interventions. We think multimodal analgesic education, coupled with easy prescription monitoring access, is a better ED option, followed by accessible addiction and long-term pain management options. Although we think seeking to match ED opioid prescribing optimally for need is important and an ongoing opportunity, we also think ceilings or other restrictive approaches through regulation will be more influential in office-based settings and longer-term care, curbing individual risk and the opioid pool more effectively. We see the harms and know the real ED role; let’s join others to educate governmental and health care leaders and advocate smart actions.

D. Prescription Opioid Shopping Does Not Increase Overdose Rates in Medicaid Beneficiaries

Sun BC, et al. Ann Emerg Med. 2018;71(6):679–687.e3

Study objective
The link between prescription opioid shopping and overdose events is poorly understood. We test the hypothesis that a history of prescription opioid shopping is associated with increased risk of overdose events.

This is a secondary analysis of a linked claims and controlled substance dispense database. We studied adult Medicaid beneficiaries in 2014 with prescription opioid use in the 6 months before an ambulatory care or emergency department visit with a pain-related diagnosis. The primary outcome was a nonfatal overdose event within 6 months of the cohort entry date. The exposure of interest (opioid shopping) was defined as having opioid prescriptions by different prescribers with greater than or equal to 1-day overlap and filled at 3 or more pharmacies in the 6 months before cohort entry. We used a propensity score to match shoppers with nonshoppers in a 1:1 ratio. We calculated the absolute difference in outcome rates between shoppers and nonshoppers.

We studied 66,328 patients, including 2,571 opioid shoppers (3.9%). There were 290 patients (0.4%) in the overall cohort who experienced a nonfatal overdose. In unadjusted analyses, shoppers had higher event rates than nonshoppers (rate difference of 4.4 events per 1,000; 95% confidence interval 0.8 to 7.9). After propensity score matching, there were no outcome differences between shoppers and nonshoppers (rate difference of 0.4 events per 1,000; 95% confidence interval –4.7 to 5.5). These findings were robust to various definitions of opioid shoppers and look-back periods.

Prescription opioid shopping is not independently associated with increased risk of overdose events.

E. Association of an Opioid Standard of Practice Intervention with IV Opioid Exposure in Hospitalized Patients

Ackerman AL, et al. JAMA Intern Med. 2018 May 14 [Epub ahead of print]

Key Points
Question  Can adopting a new standard of inpatient opioid prescribing that prefers oral and subcutaneous over intravenous administration result in reduced intravenous opioid exposure?

Findings  In this pilot study of 127 patients and 2459 patient-days on an adult medical unit, intravenous opioid dosing was reduced by 84% after adopting an opioid standard of practice, with mean pain scores similar to those before implementation of the new standard.

Meaning  This intervention may be associated with significant reduction in inpatient intravenous opioid exposure in adult medical patients; further investigation is warranted.

Importance  Opioids are commonly used to treat pain in hospitalized patients; however, intravenous administration carries an increased risk of adverse effects compared with oral administration. The subcutaneous route is an effective method of opioid delivery with favorable pharmacokinetics.

Objective  To assess an intervention to reduce intravenous opioid use, total parenteral opioid exposure, and the rate of patients administered parenteral opioids.

Design, Setting, and Participants  A pilot study was conducted in an adult general medical unit in an urban academic medical center. Attending physicians, nurse practitioners, and physician assistants who prescribed drugs were the participants. Use of opioids was compared between a 6-month control period and 3 months following education for the prescribers on opioid routes of administration.

Interventions  Adoption of a local opioid standard of practice, preferring the oral and subcutaneous routes over intravenous administration, and education for prescribers and nursing staff on awareness of the subcutaneous route was implemented.

Main Outcomes and Measures  The primary outcome was a reduction in intravenous doses administered per patient-day. Secondary measures included total parenteral and overall opioid doses per patient-day, parenteral and overall opioid exposure per patient-day, and daily rate of patients receiving parenteral opioids. Pain scores were measured on a standard 0- to 10-point Likert scale over the first 5 days of hospitalization.

Results  The control period included 4500 patient-days, and the intervention period included 2459 patient-days. Of 127 patients in the intervention group, 59 (46.5%) were men; mean (SD) age was 57.6 (18.5) years. Intravenous opioid doses were reduced by 84% (0.06 vs 0.39 doses per patient-day, P less than  .001), and doses of all parenteral opioids were reduced by 55% (0.18 vs 0.39 doses per patient-day, P  less than  .001). In addition, mean (SD) daily parenteral opioid exposure decreased by 49% (2.88 [0.72] vs 5.67 [1.14] morphine-milligram equivalents [MMEs] per patient-day). The daily rate of patients administered any parenteral opioid decreased by 57% (6% vs 14%; P less than  .001). Doses of opioids given by oral or parenteral route were reduced by 23% (0.73 vs 0.95 doses per patient-day, P = .02), and mean daily overall opioid exposure decreased by 31% (6.30 [4.12] vs 9.11 [7.34] MMEs per patient-day). For hospital days 1 through 3, there were no significant postintervention vs preintervention differences in mean reported pain score for patients receiving opioid therapy: day 1, –0.19 (95% CI, −0.94 to 0.56); day 2, −0.49 (95% CI, −1.01 to 0.03); and day 3, −0.54 (95% CI, −1.18 to 0.09). However, significant improvement was seen in the intervention group on days 4 (−1.07; 95% CI, −1.80 to −0.34) and 5 (−1.06; 95% CI, −1.84 to −0.27).

Conclusions and Relevance  An intervention targeting the use of intravenous opioids may be associated with reduced opioid exposure while providing effective pain control to hospitalized adults.

F. Opportunities for Prevention and Intervention of Opioid Overdose in the ED

Houry DE, et al. Ann Emerg Med. 2018;71(6):688-690.

Consider “Jane,” a 30-year-old female patient brought in by emergency medical services (EMS) to the emergency department (ED), reflecting just one of more than 100,000 opioid overdose patients treated in EDs each year. Naloxone, an opioid antagonist and overdose reversal drug, was administered in the field by EMS; however, additional rounds of naloxone were required in the ED because of high opioid potency. Once she was stabilized, a quick review of her chart revealed several recent visits for opioid-related overdoses. A review of her history revealed that she was prescribed opioids initially in the ED 5 years earlier after sustaining minor injuries in a motor vehicle crash. She began misusing prescription opioids during the following year, receiving prescriptions from multiple providers in primary care clinics and EDs. Yet, because a check of the state’s prescription drug monitoring program was not completed before any prescription, her use of multiple providers and high dosages was not identified, and opioids continued to be prescribed in different clinical settings for pain management. Soon thereafter, Jane initiated heroin use and presented to the ED several times with cellulitis from injection drug use, as well as after an overdose of prescription and illicit opioids. Each time, she was discharged without a referral to substance use treatment or without a naloxone kit.

Jane’s hypothetical story, although based on actual cases treated in the ED, reflects just one of many cases that continue to be on the increase. Emergency physicians, as front-line providers, without question save lives by reversing opioid overdoses, but they also have a unique opportunity to engage in prevention of a future overdose, particularly for patients who may not have other contact with the health care system. A Centers for Disease Control and Prevention (CDC) Vital Signs report has revealed that from July 2016 to September 2017, across 52 jurisdictions in 45 states, there were more than 140,000 suspected opioid-involved overdose ED visits, with a nearly 30% increase during the period.1 Increases were observed across both sexes (30% in men and 24% in women) and all age groups, with those aged 35 to 54 years representing the largest increase (36%). All regions across the United States experienced increases, but the largest increases were observed in the Midwest (70%), West (40%), and the Northeast (21%). Across 16 states with more geographically specific data available, there was a 35% increase, with continued worsening of overdose morbidity through 2017. All urbanization levels experienced increases over the time period, with significant increases in the largest cities (54%). The report relied on syndromic surveillance; that is, an approach in which near real-time data from EDs were shared and analyzed. Syndromic surveillance offers rapid data that can be used to facilitate public health action more quickly. The CDC Vital Signs report highlighted the need to better detect and respond to spikes in overdoses and to coordinate a systems-level response in communities, such as health alerts and advisories to address the ongoing opioid overdose epidemic…

G. Distribution of take-home opioid antagonist kits during a synthetic opioid epidemic in British Columbia, Canada

Irvine MA, et al. Lancet Public Health. 2018 May;3(5):e218-e225

BACKGROUND: Illicit use of high-potency synthetic opioids has become a global issue over the past decade. This misuse is particularly pronounced in British Columbia, Canada, where a rapid increase in availability of fentanyl and other synthetic opioids in the local illicit drug supply during 2016 led to a substantial increase in overdoses and deaths. In response, distribution of take-home naloxone (THN) overdose prevention kits was scaled up (6·4-fold increase) throughout the province. The aim of this study was to estimate the impact of the THN programme in terms of the number of deaths averted over the study period.

METHODS: We estimated the impact of THN kits on the ongoing epidemic among people who use illicit opioids in British Columbia and explored counterfactual scenarios for the provincial response. A Markov chain model was constructed explicitly including opioid-related deaths, fentanyl-related deaths, ambulance-attended overdoses, and uses of THN kits. The model was calibrated in a Bayesian framework incorporating population data between Jan 1, 2012, and Oct 31, 2016.

FINDINGS: 22 499 ambulance-attended overdoses and 2121 illicit drug-related deaths (677 [32%] deaths related to fentanyl) were recorded in the study period, mostly since January, 2016. In the same period, 19 074 THN kits were distributed. We estimate that 298 deaths (95% credible interval [CrI] 91-474) were averted by the THN programme. Of these deaths, 226 (95% CrI 125-340) were averted in 2016, following a rapid scale-up in distribution of kits. We infer a rapid increase in fentanyl adulterant at the beginning of 2016, with an estimated 2·3 times (95% CrI 2·0-2·9) increase from 2015 to 2016. Counterfactual modelling indicated that an earlier scale-up of the programme would have averted an additional 118 deaths (95% CrI 64-207). Our model also indicated that the increase in deaths could parsimoniously be explained through a change in the fentanyl-related overdose rate alone.

INTERPRETATION: The THN programme substantially reduced the number of overdose deaths during a period of rapid increase in the number of illicit drug overdoses due to fentanyl in British Columbia. However, earlier adoption and distribution of the THN intervention might have had an even greater impact on overdose deaths. Our findings show the value of a fast and effective response at the start of a synthetic opioid epidemic. We also believe that multiple interventions are needed to achieve an optimal impact.

H. Association of Medical and Adult-Use Marijuana Laws with Opioid Prescribing for Medicaid Enrollees

Wen H, et al. JAMA Intern Med. 2018;178(5):673-679.

Key Points
Question  Are medical and adult-use marijuana laws passed after 2010 associated with lower rates of opioid prescribing for Medicaid enrollees?

Findings  In this population-based, cross-sectional study using the all-capture Medicaid prescription data for 2011 to 2016, medical marijuana laws and adult-use marijuana laws were associated with lower opioid prescribing rates (5.88% and 6.38% lower, respectively).

Meaning  Medical and adult-use marijuana laws have the potential to lower opioid prescribing for Medicaid enrollees, a high-risk population for chronic pain, opioid use disorder, and opioid overdose, and marijuana liberalization may serve as a component of a comprehensive package to tackle the opioid epidemic.

Importance  Overprescribing of opioids is considered a major driving force behind the opioid epidemic in the United States. Marijuana is one of the potential nonopioid alternatives that can relieve pain at a relatively lower risk of addiction and virtually no risk of overdose. Marijuana liberalization, including medical and adult-use marijuana laws, has made marijuana available to more Americans.

Objective  To examine the association of state implementation of medical and adult-use marijuana laws with opioid prescribing rates and spending among Medicaid enrollees.

Design, Setting, and Participants  This cross-sectional study used a quasi-experimental difference-in-differences design comparing opioid prescribing trends between states that started to implement medical and adult-use marijuana laws between 2011 and 2016 and the remaining states. This population-based study across the United States included all Medicaid fee-for-service and managed care enrollees, a high-risk population for chronic pain, opioid use disorder, and opioid overdose.

Exposures  State implementation of medical and adult-use marijuana laws from 2011 to 2016.

Main Outcomes and Measures  Opioid prescribing rate, measured as the number of opioid prescriptions covered by Medicaid on a quarterly, per-1000-Medicaid-enrollee basis.

Results  State implementation of medical marijuana laws was associated with a 5.88% lower rate of opioid prescribing (95% CI, −11.55% to approximately −0.21%). Moreover, the implementation of adult-use marijuana laws, which all occurred in states with existing medical marijuana laws, was associated with a 6.38% lower rate of opioid prescribing (95% CI, −12.20% to approximately −0.56%).

Conclusions and Relevance  The potential of marijuana liberalization to reduce the use and consequences of prescription opioids among Medicaid enrollees deserves consideration during the policy discussions about marijuana reform and the opioid epidemic.

I. FDA Approves First Treatment For Opioid Withdrawal Symptoms

18.  ACEP Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the ED with Suspected Acute VTE Disease

Wolf SJ, et al. Ann Emerg Med. 2018;71(5):e59–e109

The 2011 American College of Emergency Physicians (ACEP) clinical policy on this topic focused on 6 critical questions: pretest probability and clinical assessment, utility of the PERC, the diagnostic role of highly sensitive D-dimer assays, computed tomography (CT) pulmonary angiogram, CT venogram, and the therapeutic role of thrombolysis in hemodynamically stable and unstable patients with PE.9

This revision will focus on 5 areas of interest or controversy that have developed or still exist since the 2011 policy was formulated. The first 2 critical questions address the role of unique clinical prediction rules and age-adjusted D-dimer testing in the diagnosis of PE, whereas the remaining 3 questions focus on optimal treatment and disposition for individuals receiving a diagnosis of venous thromboembolic disease.

The 5 Questions and Recommendations
1. In adult patients with suspected acute PE, can a clinical prediction rule be used to identify a group of patients at very low risk for the diagnosis of PE for whom no additional diagnostic workup is required?

Level B recommendation: For patients who are at low risk for acute PE, use the PERC to exclude the diagnosis without further diagnostic testing

2. In adult patients with low to intermediate pretest probability for acute PE, does a negative age-adjusted D-dimer result identify a group of patients at very low risk for the diagnosis of PE for whom no additional diagnostic workup is required?

Level B recommendation: In patients older than 50 years deemed to be low or intermediate risk for acute PE, clinicians may use a negative age-adjusted D-dimer result to exclude the diagnosis of PE.

3. In adult patients with subsegmental PE, is it safe to withhold anticoagulation?

Level C recommendations: Given the lack of evidence, anticoagulation treatment decisions for patients with subsegmental PE without associated DVT should be guided by individual patient risk profiles and preferences. [Consensus recommendation]

4. In adult patients diagnosed with acute PE, is initiation of anticoagulation and discharge from the ED safe?

Level C recommendations: Selected patients with acute PE who are at low risk for adverse outcomes as determined by PESI, simplified PESI (sPESI), or the Hestia criteria may be safely discharged from the ED on anticoagulation, with close outpatient follow-up.

5. In adult patients diagnosed with acute lower-extremity DVT who are discharged from the ED, is treatment with a NOAC safe and effective compared with treatment with LMWH and VKA?

Level B recommendations: In selected patients diagnosed with acute DVT, a NOAC may be used as a safe and effective treatment alternative to LMWH/VKA.

19. Effect of Systematic Physician Cross-checking on Reducing Adverse Events in the ED: The CHARMED Cluster Randomized Trial

Freund Y, et al. JAMA Intern Med. 2018 Apr 23 [Epub ahead of print]

Emergency departments (ED) are environments that are at high risk for medical errors. Previous studies suggested that the proportion of medical errors may decrease when more than 1 physician is involved.

To reduce the proportion of medical errors by implementing systematic cross-checking between emergency physicians.

This cluster randomized crossover trial includes a random sample of 14 adult patients (age ≥18 years) per day during two 10-day period in 6 EDs (n = 1680 patients) in France.

Systematic cross-checking between emergency physicians, 3 times a day, which included a brief presentation of one physician's case to another, followed by the second physician's feedback to the first.

Medical error in the ED, defined as an adverse event (either a near miss or a serious adverse event). The primary end point was identified using a 2-level error detection surveillance system, blinded to the strategy allocation.

Among the 1680 included patients (mean [SD] age, 57.5 [21.7] years), 144 (8.6%) had an adverse event. There were 54 adverse events among 840 patients (6.4%) in the cross-check group compared with 90 adverse events among 840 patients (10.7%) in the standard care group (relative risk reduction [RRR], 40% [95% CI, 12% to 59%]; absolute risk reduction [ARR], 4.3%; number needed to treat [NNT], 24). There was also a significant reduction rate of near misses (RRR, 47% [95% CI, 15% to 67%]; ARR, 2.7%; NNT, 37) but not of the rate of preventable serious adverse events (RRR, 29% [95% CI, -18% to 57%]; ARR, 1.2%; NNT, 83).

The implementation of systematic cross-checking between emergency physicians was associated with a significant reduction in adverse events, mainly driven by a reduction in near misses.

20. Comparative Trends in Heart Disease, Stroke, and All-Cause Mortality in the United States and a Large Integrated Healthcare Delivery System

Sidney S, et al. Am J Med. 2018 Apr 2 [Epub ahead of print].

Heart disease and stroke remain among the leading causes of death nationally. We examined whether differences in recent trends in heart disease, stroke, and total mortality exist in the United States and Kaiser Permanente Northern California (KPNC), a large integrated healthcare delivery system.

The main outcome measures were comparisons of US and KPNC total, age-specific, and sex-specific changes from 2000 to 2015 in mortality rates from heart disease, coronary heart disease, stroke, and all causes. The Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data system was used to determine US mortality rates. Mortality rates for KPNC were determined from health system, Social Security vital status, and state death certificate databases.

Declines in age-adjusted mortality rates were noted in KPNC and the United States for heart disease (36.3% in KPNC vs 34.6% in the United States), coronary heart disease (51.0% vs 47.9%), stroke (45.5% vs 38.2%), and all-cause mortality (16.8% vs 15.6%). However, steeper declines were noted in KPNC than the United States among those aged 45 to 65 years for heart disease (48.3% KPNC vs 23.6% United States), coronary heart disease (55.6% vs 35.9%), stroke (55.8% vs 26.0%), and all-cause mortality (31.5% vs 9.1%). Sex-specific changes were generally similar.

Despite significant declines in heart disease and stroke mortality, there remains an improvement gap nationally among those aged less than 65 years when compared with a large integrated healthcare delivery system. Interventions to improve cardiovascular mortality in the vulnerable middle-aged population may play a key role in closing this gap.

21. IV Fluids

A. The Association of Prehospital IV Fluids and Mortality in Patients with Penetrating Trauma

Bores SA, et al. Am J Emerg Med 2018;54(4):487–499.e6.

BACKGROUND: The optimal approach to prehospital care of trauma patients is controversial, and thought to require balancing advanced field interventions with rapid transport to definitive care.

OBJECTIVE: We sought principally to examine any association between the amount of prehospital IV fluid (IVF) administered and mortality.

METHODS: We conducted a retrospective cohort analysis of trauma registry data patients who sustained penetrating trauma between January 2008 and February 2011, as identified in the Pennsylvania Trauma Systems Foundation registry with corresponding prehospital records from the Philadelphia Fire Department. Analyses were conducted with logistic regression models and instrumental variable analysis, adjusted for injury severity using scene vital signs before the intervention was delivered.

RESULTS: There were 1966 patients identified. Overall mortality was 22.60%. Approximately two-thirds received fluids and one-third did not. Both cohorts had similar Trauma and Injury Severity Score-predicted mortality. Mortality was similar in those who received IVF (23.43%) and those who did not (21.30%) (p = 0.212). Patients who received IVF had longer mean scene times (10.82 min) than those who did not (9.18 min) (p less than 0.0001), although call times were similar in those who received IVF (24.14 min) and those who did not (23.83 min) (p = 0.637). Adjusted analysis of 1722 patients demonstrated no benefit or harm associated with prehospital fluid (odds ratio [OR] 0.905, 95% confidence interval [CI] 0.47-1.75). Instrumental variable analysis utilizing variations in use of IVF across different Emergency Medical Services (EMS) units also found no association between the unit's percentage of patients that were provided fluids and mortality (OR 1.02, 95% CI 0.96-1.08).

CONCLUSIONS: We found no significant difference in mortality or EMS call time between patients who did or did not receive prehospital IVF after penetrating trauma.

B. Are three ports better than one? An evaluation of flow rates using all ports of a triple lumen central venous catheter in volume resuscitation.

Traylor S, et al. Am J Emerg Med. 2018 May;36(5):739-740.

Poiseuille's law states flow rates are directly proportional to the radius to the 4th power and indirectly proportional to the length of a tube. Because of this property, large bore catheters are commonly used in the resuscitation of the critically ill patient. However, there are no studies comparing simultaneous use of all three lumens of a triple lumen (TL) central venous catheter (CVC) with other catheter types. Our objective was to compare the flow rates of normal saline (NS) through various resuscitation catheters against a TL CVC using all 3 ports.

We performed a blinded prospective observational study of flow rates utilizing multiple resuscitation catheters. Each catheter type was attached to a 1l bag of NS using standard saline tubing and mean time to infuse 1l of normal saline was determined. Three trials each were completed with and without pressure bags.

Simultaneous infusion of NS through all ports of a TL CVC demonstrated no statistically significant difference compared to the following catheters: 16ga peripheral venous catheter (PVC) and 6 Fr CVC with pressure bag. The 14 g PVC and 8.5Fr CVC had statistically significant faster flow rates than the TL CVC both with and without a pressure bag. The 6Fr CVC showed significantly faster flow rates than the TL CVC without a pressure bag.

Simultaneous use of all 3 ports of a TL CVC generates flow rates comparable to many other commonly used resuscitation catheters.

22. Suffering in Silence: Medical Error and its Impact on Health Care Providers.

Robertson JJ, Long B. J Emerg Med. 2018 Apr;54(4):402-409.

BACKGROUND: All humans are fallible. Because physicians are human, unintentional errors unfortunately occur. While unintentional medical errors have an impact on patients and their families, they may also contribute to adverse mental and emotional effects on the involved provider(s). These may include burnout, lack of concentration, poor work performance, posttraumatic stress disorder, depression, and even suicidality.

OBJECTIVES: The objectives of this article are to 1) discuss the impact medical error has on involved provider(s), 2) provide potential reasons why medical error can have a negative impact on provider mental health, and 3) suggest solutions for providers and health care organizations to recognize and mitigate the adverse effects medical error has on providers.

DISCUSSION: Physicians and other providers may feel a variety of adverse emotions after medical error, including guilt, shame, anxiety, fear, and depression. It is thought that the pervasive culture of perfectionism and individual blame in medicine plays a considerable role toward these negative effects. In addition, studies have found that despite physicians' desire for support after medical error, many physicians feel a lack of personal and administrative support. This may further contribute to poor emotional well-being. Potential solutions in the literature are proposed, including provider counseling, learning from mistakes without fear of punishment, discussing mistakes with others, focusing on the system versus the individual, and emphasizing provider wellness. Much of the reviewed literature is limited in terms of an emergency medicine focus or even regarding physicians in general. In addition, most studies are survey- or interview-based, which limits objectivity. While additional, more objective research is needed in terms of mitigating the effects of error on physicians, this review may help provide insight and support for those who feel alone in their attempt to heal after being involved in an adverse medical event.

CONCLUSIONS: Unintentional medical error will likely always be a part of the medical system. However, by focusing on provider as well as patient health, we may be able to foster resilience in providers and improve care for patients in healthy, safe, and constructive environments.

23. Reduction in Lactate Levels After Hemodialysis in Patients with End-Stage Renal Disease.

Hourmozdi JJ, et al. Ann Emerg Med. 2018;71(6):737-742.

Patients with end-stage renal disease commonly visit the emergency department (ED). The purpose of this investigation is to examine the prevalence of baseline abnormal lactate levels and to evaluate the effects of hemodialysis on serum lactate levels.

This was a prospective observational cohort study performed at an outpatient dialysis facility at an urban tertiary care hospital. The study consisted of 226 patients with end-stage renal disease who were receiving long-term hemodialysis and were enrolled during a 2-day period at the beginning of December 2015. Blood drawn for lactate levels was immediately analyzed before and after hemodialysis sessions. All patients completed their hemodialysis sessions.

The prevalence of an abnormal lactate level (greater than 1.8 mmol/L) before hemodialysis was 17.7% (n=40). Overall, lactate levels decreased by 27% (SD 35%) after hemodialysis, with a decrease of 37% (SD 31%) for subgroups with a lactate level of 1.9 to 2.4 mmol/L, and 62% (SD 14%) with a lactate of 2.5 to 3.9 mmol/L.


The data presented help providers understand the prevalence of abnormal lactate values in an outpatient end-stage renal disease population. After hemodialysis, lactate levels decreased significantly. This information may help medical providers interpret lactate values when patients with end-stage renal disease present to the ED.

24. Micro Bits

A. Vertebroplasty no better than sham procedure for painful acute osteoporotic vertebral compression fractures (VERTOS IV): randomised sham controlled clinical trial

B. Satirical post: Ortho Consults Medicine to See if It’s Spelled Orthopedics or Orthopaedics

C. MRI Glove Gives Doctors a Deeper Look at the Hand

A new kind of MRI component in the shape of a glove delivers the first clear images of bones, tendons and ligaments moving together, a new study finds.

Led by NYU School of Medicine and just published in Nature Biomedical Engineering, the study shows how a new MRI element design woven into garment-like detectors can capture high-quality images of moving joints for the first time.

D. Some oral antibiotics tied to kidney stone risk

Children and adults who took sulfas, cephalosporins, fluoroquinolones, nitrofurantoin/methenamine or broad-spectrum penicillins -- all oral antibiotics -- three to 12 months prior to an index date were more likely to develop nephrolithiasis, according to a study in the Journal of the American Society of Nephrology. Researchers found the strongest risk relationship between antibiotics and risk of kidney stones among those younger than 18 and those exposed three to six months before the index date.

E. First-Ever Suicide Prevention Recommendations Released

Guidelines can be found here:

F. Myocardial Infarction with Nonobstructive Coronary Arteries: The Importance of Achieving Secondary Prevention Targets

G. Nationwide Trends in Mortality Following Penetrating Trauma: Are We Up for the Challenge?

H. Alcohol consumption may impair sleep quality

A study reported in JMIR Mental Health found alcohol intake, even at low or moderate levels, was associated with less restorative sleep. The findings, based on data from 4,098 men and women ages 18 to 65, showed the effect of alcohol intake was more apparent among younger individuals than older ones.

I. Bacterial treatment may benefit youths, adults with eczema

Four in 5 children and 6 in 10 adults with eczema who sprayed their skin with sugar water containing increasing doses of live Roseomonas mucosa bacteria taken from individuals without eczema had their symptoms improve by more than 50%, according to a study in JCI Insight. The findings also showed no complications from the bacterial treatment.

J. Single-Dose Packaging May Reduce Kids’ Unintentional Exposure To Narcotic Medicines, Research Suggests.

K. Palliative care reduces hospital costs, stays, study finds

Adding a palliative care consultation within three days of hospital admission reduced per-patient costs by an average of $3,237, compared with not providing the consult, according to a study in JAMA Internal Medicine. Palliative care's effect on the length and cost of a hospital stay was greater for patients with four or more comorbidities than it was for those with two or fewer comorbidities.

L. No Radiographic Safe Margin Found in the “Easy IJ” Internal Jugular Vein Procedure

M. Who Should Perform REBOA Technique? Guideline Limiting Emergency Physician Use Draws Fire

N. New Rabies Test May Transform Animal-Bite Treatment: Molecular assay quickly and accurately determines if animals are infected

O. Will Posting Nutritional Information on Menus Prod Diners to Make Healthier Choices?