October 2016 Featured Articles, Volume 223

CONTINUING MEDICAL EDUCATION PROGRAM

October 2016 Featured Articles, Volume 223

Get credit right away by taking all CME tests online http://jacscme.facs.org Article 1: Burn, Trauma, Critical Care; General Surgery

Timing of pharmacologic venous thromboembolism prophylaxis in severe traumatic brain injury: a propensity-matched cohort study. Byrne JP, Mason SA, Gomez D, et al. J Am Coll Surg 2016;223:621e631 Article 2: General Surgery

Interval appendectomy: finding the breaking point for cost-effectiveness. Senekjian L, Nirula R, Bellows B, Nelson R. J Am Coll Surg 2016;223:632e643

Objectives: After reading the featured articles published in this issue of the Journal of the American College of Surgeons (JACS) participants in this journal-based CME activity should be able to demonstrate increased understanding of the material specific to the article featured and be able to apply relevant information to clinical practice. A score of 75% is required to receive CME and Self-Assessment credit. The JACS Editor-in-Chief does not assign a manuscript for review to any person who discloses a conflict of interest with the content of the manuscript. Two articles are available each month in the print version, and usually 4 are available online for each monthly issue, going back 24 months.

ARTICLE 1 (Please consider how the content of this article may be applied to your practice.)

Timing of pharmacologic venous thromboembolism prophylaxis in severe traumatic brain injury: a propensity-matched cohort study Byrne JP, Mason SA, Gomez D, et al. J Am Coll Surg 2016;223:621e631 Learning Objectives: After study of this article, surgeons should understand the current evidence surrounding venous thromboembolism (VTE) prophylaxis practices in patients with severe traumatic brain injury (TBI), and be better positioned to inform up-to-date thromboprophylaxis guidelines specific to these patients at their institution.

Accreditation: The American College of Surgeons is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Question 1 Which statement summarizes the current recommendations of evidence-based thromboprophylaxis guidelines with respect to the optimal timing for initiation of prophylaxis in patients with severe traumatic brain injury?

Designation: The American College of Surgeons designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit
. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

ª 2016 Published by Elsevier Inc. on behalf of the American College of Surgeons.

a) Prophylaxis with low molecular weight heparin (LMWH) or unfractionated heparin (UH) should be initiated within 48 hours of arrival at the hospital, except in patients who demonstrate change in size of intracranial hemorrhage on repeated head CT scan. b) LMWH or UH should be initiated within the first 72 hours. Where pharmacologic prophylaxis is

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contraindicated, insertion of an inferior vena cava filter should be considered. c) No recommendations are made for the optimal timing of thromboprophylaxis initiation. d) LMWH or UH should be initiated within 24 hours of arrival. Mechanical prophylaxis should be used in all patients. Where pharmacologic prophylaxis is contraindicated, insertion of an inferior vena cava filter should be considered. e) Prophylaxis with LMWH or UH should be initiated early, once repeated head CT demonstrates stability of intracranial hemorrhage. Critique: There is limited high quality evidence to inform the safe and effective initiation of VTE prophylaxis in patients with TBI, and the timing of prophylaxis initiation in this patient population is not addressed in current guidelines. The most recent CHEST guidelines state the following for patients with major trauma, including TBI: “For major trauma patients, we suggest use of low-dose unfractionated heparin (Grade 2C), low molecular weight heparin (Grade 2C), or mechanical prophylaxis, preferably with intermittent pneumatic compression (Grade 2C), over no prophylaxis.” A recent systematic review by Chelladurai et al (2013) concluded that there was insufficient evidence to comment on the effectiveness or optimal timing for initiation of thromboprophylaxis in patients with severe TBI. Our study aimed to address this gap in the literature. Question 2 The most common agents used for thromboprophylaxis are LMWH and UH. Which of the following statements summarizes the current evidence for selecting LMWH or UH for thromboprophylaxis in patients with severe TBI? a) Current evidence suggests that UH is safer for use in patients with severe TBI because shorter half-life and opportunity for reversal with protamine sulfate are associated with lower risk of hemorrhagic complication. b) At present, there is no evidence suggesting that one agent is more effective at preventing thromboembolism or safer in patients with severe TBI. c) Current evidence suggests that LMWH may be more effective than UH at preventing thromboembolism in patients with severe TBI. d) Although LMWH is more effective at preventing thromboembolism in patients with severe TBI, it is more associated with complications related to intracranial hemorrhage compared with UH.

e) UH should be the agent of choice for thromboprophylaxis in patients with severe TBI because UH is more effective at preventing thromboembolism, and is safer, than LMWH. Critique: Both UH and LMWH act via interaction with antithrombin III. Unfractionated heparin is a mixture of molecules varying in molecular size (3e30 kDA) and chemical activity. Low molecular weight heparin contains molecules of smaller size (<8 kDA), which more specifically accelerate inactivation of factor Xa. Longer elimination half-life allows for once-daily dosing of LMWH. Although practitioners may have traditionally favored the use of UH for thromboprophylaxis in patients with severe TBI due to the perception that shorter half-life might be associated with a lower risk of intracranial hemorrhage, there is a lack of evidence to support this practice. At present, there is no evidence to support the notion that one agent is safer than the other. Although there is no level I evidence comparing the use of LMWH vs UH in patients with severe TBI, there is evidence that LMWH is more effective than UH at preventing thromboembolism in patients with major trauma. Geerts et al (1996) demonstrated, in a randomized controlled trial (RCT), that LMWH was associated with lower rates of deep vein thrombosis compared with UH in patients with severe injury. Results from the PROTECT trial, an international multicenter RCT comparing LMWH with UH in critically ill patients, found that LMWH was significantly associated with lower rates of pulmonary embolism. The study examined in this article presented an analysis of patients with severe TBI, showing that LMWH was associated with lower risk of thromboembolism compared with UH (odds ratio 0.60; 95% CI 0.44 to 0.82). Question 3 Which score or set of criteria may be used as an objective assessment of the risk of intracranial hemorrhage (ICH) progression, to guide the timing of initiation of thromboprophylaxis? a) b) c) d)

Glasgow Coma Scale motor component Total Glasgow Coma Scale score Modified Berne-Norwood criteria Venous thromboembolism risk assessment profile (RAP) e) Intracerebral hemorrhage score

Critique: Radiologic and clinical features that have been evaluated to assess the risk of ICH progression

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include presence and size of hemorrhage, cerebral contusion, intraventricular hemorrhage, abnormal CT angiogram, intracranial monitor placement, craniotomy, and evidence of ICH progression on repeated head CT. These features are encompassed in the Modified Berne-Norwood criteria. The Modified BerneNorwood criteria stratify patients into low risk (no moderate- or high-risk criteria), moderate risk (subdural or epidural hematoma > 8 mm, contusion or intraventricular hemorrhage > 2 cm, subarachnoid hemorrhage with abnormal CT angiogram, progression of ICH at 24 hours), or high risk (intracranial pressure monitor placement, craniotomy, evidence of ICH progression at 72 hours) of hemorrhage progression. The American College of Surgeons Trauma Quality Improvement Program has published the “Best Practices in Management of Traumatic Brain Injury,” outlining recommendations for initiation of thromboprophylaxis based on the Berne-Norwood criteria using the limited evidence that exists. The Glasgow Coma Scale cannot be used to estimate risk of hemorrhage progression. The intracerebral hemorrhage score is used to estimate mortality in patients with traumatic brain injury. Question 4 Using the modified Berne-Norwood criteria to stratify risk of intracranial hemorrhage (ICH) progression, which of the following is correct regarding the American College of Surgeons Trauma Quality Improvement Program (ACS TQIP) Best Practices in Management of Traumatic Brain Injury recommendations for initiating thromboprophylaxis? a) In patients who are low-risk, pharmacologic prophylaxis should be initiated at 72 hours if repeated head CT demonstrates stable ICH. b) In patients who meet moderate-risk criteria or demonstrate progression of ICH at 24 hours, prophylaxis can be initiated at 72 hours with low risk of progression if repeated CT head at 72 hours demonstrates no ICH progression. c) In patients who meet moderate- or high-risk criteria, pharmacologic prophylaxis should be deferred indefinitely. Mechanical prophylaxis measures should be used. d) Pharmacologic prophylaxis should be initiated at 72 hours in patients who meet high-risk criteria. e) In patients who meet low-risk criteria, prophylaxis should be initiated at 24 hours. Inferior vena cava filter insertion should be considered in patients who meet moderate- or high-risk criteria.

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Critique: Providing the only level I evidence on this topic, Phelan et al (2012) evaluated the use of a protocol for initiating pharmacologic thromboprophylaxis in patients with TBI. This protocol stratified patients into low-, moderate-, or high-risk groups based on the Modified Berne-Norwood criteria. The study provided initial results for the low-risk subgroup, finding that initiation of prophylaxis could be accomplished without increased risk of ICH progression in patients who were low-risk, without evidence of progression of ICH on repeated CT head at 24 hours. The ACS TQIP Best Practices for Management of TBI recommend that prophylaxis be initiated in patients who are low risk, without progression on head CT, at 24 hours. In patients who meet moderate criteria, pharmacologic prophylaxis should be deferred for 72 hours, at which point prophylaxis should be initiated if repeated head CT demonstrates stable ICH. Patients who meet high-risk criteria are difficult to manage because such patients are often excluded from observational studies. Inferior vena cava filter insertion may be considered in high-risk patients.

ARTICLE 2 (Please consider how the content of this article may be applied to your practice.)

Interval appendectomy: finding the breaking point for cost-effectiveness Senekjian L, Nirula R, Bellows B, Nelson R J Am Coll Surg 2016;223:632e643 Learning Objectives: After study of this article the surgeon should understand that it might be costeffective for some patients to be treated with interval appendectomy after initial nonoperative management. However, there is an age cut-off at which it ceases to be cost-effective. The surgeon should also understand that patient characteristics should continue to dictate patient care, but cost might influence the way that surgeons practice. Additionally, the surgeon should understand that although surgery is a costly event, delay in diagnosis of cancer or inflammatory bowel disease can increase those costs over time. Question 1 What is the probability of recurrence of appendicitis within 1 year after treatment of perforated appendicitis without surgery? a) 0% b) 5% c) 12%

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d) 20% e) 50%

was calculated to determine which strategy was most cost-effective.

Critique: Recurrence of appendicitis is a risk when patients are treated without surgical intervention. There is a range of probabilities of recurrence, but recurrence appears to be the most likely within the first year. In this study, the percent probability of recurrent appendicitis (11.6  5.6) was determined from previous data extraction from a number of previous publications.

Question 3 In which of the following cases is interval appendectomy after nonoperative management cost-effective?

Question 2 When comparing base case analysis and probabilistic sensitivity analysis (PSA), which of the following is true? a) The number of simulations is greater with base case, creating a more accurate model. b) PSA addresses uncertainty by taking model and patient variability into account. c) There is no difference between base case and PSA beyond additional runs of the model itself. d) Base case is a 2-dimensional model, PSA is 1-dimensional. e) Base case analyses take more effort to run and are more labor intensive and are therefore slower. Critique: In a “base case” analysis, clinical parameters are assigned; for example, a patient age and outcomes are assessed under a range of other clinical assumptions, keeping the “base case” assumptions a constant. Base case analysis uses mean values of each parameter as determined in previous trials and databases. Probabilistic sensitivity analysis (PSA) allows numerous parameters to be varied simultaneously to address uncertainty in the estimates of the values. Base case models are faster to run, and this model was run at ages 18, 35, and 50 years. Base case uses mean values, whereas PSA can use ranges. PSA was run at incremental ages to determine if there was a dominant strategy. The dominant strategy was interval appendectomy at ages 18 to 29 years. No interval appendectomy was dominant at ages 46 to 60 years. For patients aged 30 to 45 years, the interval cost-effectiveness ratio

a) In all patients b) It is never cost-effective and should not be performed c) For patients age 33 to 50 years d) For patients age 18 to 33 years e) For patients age 50 to 60 years Critique: Cost-effectiveness depends on willingness to pay. The cost chosen for this model was based on the standard value, generally set at $50,000. Costeffectiveness is based on many factors, but was clearly influenced by patient age. Determining the need for interval appendectomy in this setting is based on cost and utility, but clinical judgment is key when taking care of the individual patient. Using a willingness-to-pay threshold of $50,000/quality-adjusted life year, interval appendectomy remains cost effective for patients aged 18 to 33 years. Question 4 When utilities are discussed in this study: a) They are measured on a scale from 0 to 100. b) Zero represents perfect health. c) They are outcome measurements that adjust for patient preference. d) They do not vary throughout a patient’s life. e) One represents death of the patient. Critique: Utilities are used here as a measure of how patients perceive their own health. Tufts CostEffectiveness Registry has compiled a large number of utilities for various patient health states. Utilities may vary based on patient population, but this registry has determined valid utilities to use in this study. In our evaluation, outcomes were adjusted for patient preference, or utility, which is measured in a 0-to-1 scale. One indicates perfect health and 0 is death.

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October 2016 Featured Articles, Volume 223 Timing of pharmacologic venous thromboembolism prophylaxis in severe traumatic brain injury: a propensity-matched cohort study Byrne JP, Mason SA, Gomez D, et al. J Am Coll Surg 2016;223:621e631 Interval appendectomy: finding the breaking point for cost-effectiveness Senekjian L, Nirula R, Bellows B, Nelson R. J Am Coll Surg 2016;223:632e643