Medicolegal Issues

ITL: Physician Reviews of HM-Relevant Research


In This Edition

Literature At A Glance

A guide to this month’s studies

  1. Online calculator helps prevent post-op respiratory failure
  2. New drug for long-term treatment of PE
  3. Benefits of triple therapy for COPD
  4. Knee-length compression stockings as good as thigh-length for PTS
  5. Video monitoring improves hand hygiene
  6. Asymptomatic bacteriuria often misdiagnosed as UTI
  7. CT accurate for lower GI bleeding diagnosis
  8. Switch from albuterol to lavalbuterol to reduce tachycardia not recommended

Preoperative Risk Calculator Can Help Predict Postoperative Respiratory Failure

Clinical question: Can preoperative factors identify patients at risk for postoperative respiratory failure (PRF)?

Background: PRF—when a patient requires mechanical ventilation >48 hours after surgery or needs unplanned intubation within 30 days of surgery—is associated with high mortality, with 30-day mortality rates of 26%.

Study design: Analysis of multicenter, prospective databases of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP).

Setting: Analysis of NSQIP data from 2007 (training set) and 2008 (validation set).

Synopsis: PRF was seen in 3.1% of patients in the 2007 data set and 2.6% in the 2008 data set. Those with PRF had significantly higher mortality rates than those without PRF (25.62% vs. 0.98%; P<0.0001). Preoperative risk factors associated with significantly increased risk of PRF were American Society of Anesthesiologists’ class, functional status, emergent nature of procedure, type of surgery, and preoperative sepsis.

The 2007 data set was used to develop the model, and the 2008 data set was used as a validation set. The selected risk model showed similar results in both sets with a c-statistic of 0.91 in the training set and 0.90 in the validation set. This selected model was then used to develop an interactive calculator predicting PRF (available at

Bottom line: The PRF risk calculator can identify patients at high risk for PRF, which can aid in tailoring preventive strategies for patients prior to surgery.

Citation: Gupta H, Gupta PK, Fang X, et al. Development and validation of a risk calculator predicting postoperative respiratory failure. Chest. 2011;140:1207-1215.

New Drug for Treatment of Acute Symptomatic Pulmonary Embolism

Clinical question: Is the incidence of recurrent venous thromboembolism (VTE) or bleeding with use of idrabiotaparinux comparable to warfarin for treatment of acute symptomatic pulmonary embolism (PE)?

Background: Warfarin is an effective treatment for PE; however, maintenance of effective and safe levels of anticoagulation is difficult to achieve. A straightforward treatment option would be an attractive alternative. Idrabiotaparinux, a factor Xa inhibitor bound with a biotin moiety, is a weekly subcutaneous injection proposed as an alternative to warfarin for treatment of PE.

Study design: Industry-sponsored double-blind, randomized controlled trial.

Setting: 291 centers in 37 countries.

Synopsis: A group of 3,202 patients aged 18 to 96 years were randomly assigned to receive enoxaparin, followed by idrabiotaparinux or enoxaparin, then overlapped and followed by warfarin for three or six months. The incidence of recurrent VTE (including fatal and nonfatal PE or deep vein thrombosis) did not differ between the two treatment arms.

Of the 1,599 patients treated with idrabiotaparinux, 48 (3%) had a recurrence; of the 1,603 treated with warfarin, 97 (6%) had a recurrence (odds ratio, 0.49). The rate of clinically relevant bleeding was also similar, with 72 (5%) in the idrabiotaparinux group versus 106 (7%) in the warfarin group. Much like warfarin, idrabiotaparinux requires bridging therapy with initial low-molecular-weight heparin.

Bottom line: Use of enoxaparin followed by weekly subcutaneous injection of idrabiotaparinux was as effective as enoxaparin followed by warfarin for preventing recurrent VTE, and may provide a suitable option for treatment of acute symptomatic PE.

Citation: Buller HR, Gallus AS, Pillion G, Prins MH, Raskob GE. Enoxaparin followed by once-weekly idrabiotaparinux versus enoxaparin plus warfarin for patients with acute symptomatic pulmonary embolism: a randomised, double-blind, double-dummy, non-inferiority trial. Lancet. 2012;379:123-129.

Triple Therapy Better than Double for COPD

Clinical question: Does addition of tiotropium to inhaled corticosteroids and long-acting beta-agonists (LABA) have an additive benefit in reducing mortality, hospital admissions, and exacerbations in COPD?

Background: Triple therapy in COPD involves adding LABA and long-acting antimuscarinics (LAMA), such as tiotropium, to inhaled corticosteroids (ICS). Despite the guidelines recommending triple therapy for severe COPD, most studies have evaluated either LAMA or LABA plus ICS, but not all three together.

Study design: Retrospective cohort.

Setting: Tayside, Scotland’s National Health Services database.

Synopsis: Patients with severe COPD were divided into two groups: 1,857 patients had received ICS+LABA (double therapy) and 996 had received ICS+LABA+tiotropium (triple therapy), with follow-up of 4.65 years.

All-cause mortality was 35% lower in the triple therapy group (HR 0.65, 95% CI 0.57-0.75). Corticosteroid use was 29% lower (HR 0.71, 95% CI 0.63-0.80), and hospital admissions were 15% lower (HR 0.85, 95% CI 0.73-0.99) in the triple-therapy group. These results were adjusted for smoking, age, sex, socioeconomic status, and history of diabetes, cardiovascular, and respiratory disease.

This study is limited by its observational retrospective design but provides good evidence of the need for randomized controlled trials to validate the clinical benefits of triple therapy.

Bottom line: Adding tiotropium to ICS plus LABA is associated with lower all-cause mortality, hospitalizations, and corticosteroid use when compared with ICS plus LABA, validating its current use in management of severe COPD.

Citation: Short PM, Williamson PA, Elder DHJ, Lipworth SIW, Schembi S, Lipworth BJ. The impact of tiotropium on mortality and exacerbations when added to inhaled corticosteroids and long-acting β-agonist therapy in COPD. Chest. 2012;141:81-86.

Above-Knee Compression Stockings Not Better than Below-Knee Stockings for Protection Against Post-Thrombotic Syndrome

Clinical question: Do above-knee compression elastic stockings prevent post-thrombotic syndrome (PTS) better than below-knee stockings?

Background: PTS—characterized by leg pain, cramps, edema, and hyperpigmentation—occurs in 25% to 50% of patients after an episode of deep venous thrombosis (DVT). Previous studies demonstrated a 50% reduction in the incidence of PTS when patients used below-knee stockings.

Study design: Open-label, randomized clinical trial.

Setting: Eight hospitals in Italy.

Synopsis: A total of 267 patients with their first episode of DVT were randomized to thigh-length or below-knee compression elastic stockings, as well as therapeutic anticoagulation, with a primary endpoint of three-year incidence of PTS. Assessment was done by study personnel who were blinded to the type of stocking the patients had been prescribed. Severity of PTS was graded by a scoring system incorporating objective and subjective criteria with an independent adjudicator.

The intention-to-treat analysis showed no significant difference in the three-year incidence of PTS between thigh- and knee-length stockings (32.6% vs. 35.6%, respectively). Compliance was better in the knee-length (82.6%) than in the thigh-length (66.7%) group due to the significantly lower rate of stockings-related side effects.

The study is limited by a lack of blinding in the study participants.

Bottom line: Knee-length stockings offer equal similar protection against PTS with better compliance when compared with thigh-length stockings.

Citation: Prandoni P, Noventa F, Quintavalla R, et al. Thigh-length versus below-knee compression elastic stockings for prevention of the post-thrombotic syndrome in patients with proximal-venous thrombosis: a randomized trial. Blood. 2012;119:1561-1565.

Video Auditing With Near- Real-Time Feedback Improves Hand Hygiene Practices

Clinical question: Does the use of direct video monitoring with continuous, multi-modal feedback promote improvement in healthcare workers’ compliance with hand hygiene?

Background: Appropriate hand hygiene is an effective means of infection control. Direct human observation of hand hygiene compliance does little more than provide a biased, temporary, and often overestimated assessment of compliance. The use of video-based monitoring technology in other aspects of society (e.g. traffic signal cameras) has been well demonstrated to modify behavior.

Study design: Prospective cohort study.

Setting: Tertiary-care hospital’s 17-bed medical ICU in the northeastern U.S.

Synopsis: Through the use of 21 motion-activated video cameras with continuous third-party auditing, the provision of near real-time feedback improved hand hygiene rates of healthcare workers from 6.5% to 81.6%. In the four months preceding feedback, only 3,933 hand-washing events out of 60,542 (6.5%) were considered “passing.” During the active feedback period, 59,627 events out of 73,080 (81.6%) passed.

The improvement was sustained in the maintenance period of the study with an average rate of hand hygiene compliance of 87.9%. The improvement in hand hygiene compliance required active provision of feedback as well as the presence of monitoring equipment, making the applicability of this study limited, based on the cost of the technology and the manpower to provide feedback.

Bottom line: Hand hygiene practices improve when healthcare workers are given immediate feedback on their compliance.

Citation: Rebellion D, Husain E, Schilling ME, et al. Using high-technology to enforce low-technology safety measures: the use of third-party remote video auditing and real-time feedback in healthcare. Clin Infect Dis. 2012:54(1):1-7.

Mismanagement of Enterococcal Bacteriuria

Clinical question: Are clinical providers following appropriate guidelines to identify and manage enterococcal bacteriuria?

Background: There are specific evidence-based guidelines for the diagnosis and treatment of urinary tract infections (UTI) and asymptomatic bacteriuria (ABU). ABU is often mistaken for a UTI, and incorrectly treated as one.

Study design: Retrospective cohort.

Setting: Two academic teaching hospitals in Houston, Texas.

Synopsis: Using the current Infectious Disease Society of America (IDSA) guidelines, 375 Enterococcus urine cultures were reviewed and determined to be either UTI or ABU. The cultures were initially reviewed for appropriate treatment and again 30 days later for complications. UTI was defined as bacteriuria with one or more sign or symptom (urgency, frequency, dysuria, suprapubic tenderness, flank pain, rigors, visible hematuria, delirium, or fevers) without another identifiable cause. ABU was defined as bacteriuria without any of the signs or symptoms, or a clear nonurinary source.

Of the 339 cultures matching inclusion criteria, 156 were classified as UTI and 183 classified as ABU. Sixty of the 183 ABU (32.8%) were inappropriately treated with antibiotics, while antibiotics were withheld in 23 of the 156 UTI (14.7%). Eighty-three of 339 cultures (24.5%) were incorrectly treated. The most common reason for ABU being inappropriately treated was the presence of pyuria, associated with a threefold higher use of antibiotics.

There was no significant difference in subsequent infections or infectious complications between UTI and ABU.

Bottom line: Enterococcal ABU is frequently treated with antibiotics, even though guidelines recommend against it; providers should resist overtreating enterococcal ABU.

Citation: Lin E, Bhusal Y, Horwitz D, Shelburne SA, Trautner BW. Overtreatment of enterococcal bacteriuria. Arch Intern Med. 2012;172:33-38.

CT Angiography for the Diagnosis of Acute Lower GI Bleeding in an Emergency Setting

Clinical question: Is CT angiography a reliable initial diagnostic procedure to identify the presence and location of an acute lower gastrointestinal (GI) bleed in the ED setting?

Background: CT angiography has been identified as a potentially useful procedure to identify acute GI bleeds; however, the specific role and timing of the procedure has not been clearly identified.

Study design: Prospective study.

Setting: ED of a university-based hospital in Madrid.

Synopsis: CT angiography was performed on 47 ED patients (27 men, 20 women, with a mean age of 68 years) with an acute lower GI bleed. Study protocol included a preliminary unenhanced CT scan followed by CT angiogram prior to the standard clinical protocol, which included colonoscopy, angiography, or laparotomy.

Images were reviewed by two different ED radiologists, who were blinded to the diagnosis, and compared with the standard protocol findings. CT angiography correctly identified active acute or recent GI bleeding in 46 of the 47 patients, with a sensitivity of 100% (19 of 19), NPV of 100% (27 of 27), specificity of 96% (27 of 28), and PPV of 95% (19 of 20). CT angiography also was 93% accurate in identifying the cause of the GI bleed when compared with the standard reference.

Limitations of the study include its small size and the lack of a control group.

Bottom line: CT angiography is an accurate and more readily available modality for the diagnosis of acute lower GI bleeding, though it does not provide a therapeutic option.

Citation: Martí M, Artigas JM, Garzón G, Alvarez-Sala R, Soto JA. Acute lower intestinal bleeding: feasibility and diagnostic performance of CT angiography. Radiology. 2012;262:109-116.

Substitution of Levalbuterol to Avoid Tachyarrhythmia Not Supported

Clinical question: Does substitution of levalbuterol for albuterol in critically ill adult patients result in decreased incidence of tachyarrhythmias?

Background: Studies have indicated an increased risk of mortality from tachycardia and tachyarrhythmias in ICU patients. Levalbuterol is the R-isomer of albuterol, and it has been proposed that it may mitigate cardiac side effects seen with beta-2 agonists. For this reason, some clinicians have advocated using nebulized levalbuterol in critically ill patients.

Study design: Prospective randomized controlled trial with patient crossover.

Setting: Single academic medical center.

Synopsis: All ICU patients in a single teaching hospital were screened, and 70 patients were included. Patients were randomly crossed over between albuterol and levalbuterol every four to six hours. This resulted in a total of 836 measurements of heart rate, the primary outcome measurement. The study showed no clinically significant differences in average heart rate when using levalbuterol versus albuterol. This was a small study of ICU patients, using a surrogate endpoint of heart rate rather than mortality. Furthermore, the assessment of tachyarrhythmias was limited given the study size and relative rarity of these events. Despite these limitations, the study casts significant doubt on the theory and practice of switching from albuterol to levalbuterol solely for the purpose of reducing or avoiding tachycardia or tachyarrhythmias.

Bottom line: Substitution of levalbuterol for albuterol to avert tachycardia in critically ill patients is not warranted.

Citation: Khorfan FM, Smith P, Watt S, Barber KR. Effects of nebulized bronchodilator therapy on heart rate and arrhythmias in critically ill adult patients. Chest. 2011;140:1466-1472.

Clinical Shorts


A survey demonstrated that trainees are exposed to defensive medicine practices, including decision-making guided by perceived malpractice risk and intentionally failing to report medical errors.

Citation: O’Leary KJ, Choi J, Watson K, Williams MV. Medical students’ and residents’ clinical and educational experiences with defensive medicine. Acad Med. 2012:87:142-148.


Meta-analysis of 10 randomized controlled trials demonstrated that therapy with aliskiren and an ACEI or ARB increases the relative risk of hyperkalemia by approximately 50%.

Citation: Harel Z, Gilbert C, Wald R, et. al. The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalemia and acute kidney injury: systematic review and meta-analysis. BMJ. 2012;344:1-13.


A meta-analysis of randomized controlled trials of dabigatran showed an association between dabigatran use and an increased risk of acute coronary events, suggesting the need for further study.

Citation: Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials. Arch Intern Med. 2012.172:397-402.


In a head-to-head clinical trial, patients taking Bydureon (extended-release exenatide) were found to have a statistically significant reduction in hemoglobin A1C when compared with Byetta (twice-daily exenatide).

Citation: Amylin Pharmaceuticals Inc. FDA approves Bydureon—the first and only once-weekly treatment for Type 2 diabetes. PR Newswire website. Available at: Accessed April 1, 2012.

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