Recent Research

Reducing MRSA in the ICU, rivaroxaban in heart failure, warfarin bridging during cardiac device surgery, and more.


Universal decolonization beats other strategies for reducing MRSA in ICU

Universal decolonization is more effective than targeted decolonization or screening and isolation, for reducing MRSA and other infections in the ICU, a study found.

Researchers randomly assigned 43 hospitals to one of three strategies, with all adult ICUs in a single hospital given the same strategy. Group 1 did bilateral screening of the nares for methicillin-resistant Staphylococcus aureus (MRSA) on ICU admission, with contact precautions implemented for carriers of MRSA or other multi-drug resistant pathogens. In group 2, screening and contact precautions were similar to group 1, but patients with known MRSA colonization or infection underwent a five-day decolonization regimen of daily chlorhexidine bathing and twice-daily intranasal mupirocin. For group 3, there was no MRSA screening on ICU admission, and contact precautions resembled group 1. All patients received twice-daily intranasal mupirocin for five days, and daily chlorhexidine bathing for the whole ICU stay. The main outcome was ICU-attributable, MRSA-positive clinical cultures, and secondary outcomes were ICU-attributable bloodstream infection caused by MRSA or any pathogen.

Universal decolonization (group 3) led to a significantly greater reduction in the rate of all bloodstream infections than either of the other two groups, with one bloodstream infection prevented per 54 patients who underwent decolonization. For the main outcome of MRSA-positive cultures, hazard ratios (HR) differed significantly among the groups in the baseline vs. intervention period (0.92 for group 1, 0.75 for group 2, 0.63 for group 3; P=0.01). The same was true for bloodstream infection with any pathogens (HR, 0.99, 0.78 and 0.56, respectively; P<0.001). Mild adverse events related to chlorhexidine occurred in seven patients. Results were published in the June 13 New England Journal of Medicine.

Universal decolonization was implemented as part of routine practice, using the existing infrastructure for a given hospital (including community hospitals), so the results should be generalizable, the authors wrote. However, if universal decolonization is implemented widely, there will need to be surveillance programs to watch for mupirocin and chlorhexidine resistance, they warned.

Since active detection and isolation don't appear to work for controlling MRSA, hospitals should discontinue this practice and laws requiring MRSA screening in ICUs should be repealed, editorialists wrote. Health professionals should keep the results of this study in mind when discussing methods of controlling other emerging drug-resistant pathogens, as well, they added.

Troponin monitoring may predict death after non-cardiac surgery

Postoperative monitoring of cardiac troponin may help improve the prognosis of patients who undergo noncardiac surgery, the authors of a study wrote.

In a single-center, observational study, researchers examined records of 2,232 consecutive intermediate- to high-risk noncardiac surgery patients in the Netherlands who were at least 60 years old when they had surgery in 2011. According to hospital protocol, cardiac troponin I (TnI) measurements were ordered for the first three days after surgery. Myocardial injury was defined by researchers as a TnI >0.06 µg/L. The main outcome was all-cause mortality within 30 days after surgery, and secondary outcomes were length of stay and postoperative myocardial infarction (MI). Results were published in the June 11 Circulation.

Postoperative myocardial injury was associated with a higher risk of death: 8.6% of patients with myocardial injury died within 30 days compared to 2.2% of patients with normal TnI levels (P<0.01). The median time of death after TnI elevation was 12 days. The unadjusted relative risk of death was 3.0 with a minor increase in TnI (0.07 to 0.59 µg/L) and 7.9 in case of a 10-fold increase or higher in TnI (≥0.60 µg/L). After adjustment of the association between myocardial injury and death for variables known to predict postoperative cardiovascular events, only emergency surgery and TnI were significantly related to death within 30 days (relative risk, 2.4 with minor TnI increase vs. 4.2 with 10-fold or higher increase; P<0.01). Patients with myocardial injury stayed in the hospital a median of 10 days versus five days for those without such injury (P<0.01). An MI was diagnosed in 10 patients; one of these had an ST-elevation MI.

The association of TnI with death was dependent on the degree of the TnI elevation (relative risk between 2.4 and 4.2), the authors noted, but was independent of preoperative factors known to place one at risk of postoperative death. As such, postoperative troponin monitoring is feasible as the standard of care and could improve risk stratification and classification of patients who are at risk for early postoperative death, they wrote. “The time interval between troponin elevation and death potentially allows physicians to modify prognosis,” they concluded.

An editorialist wrote, however, that it's not clear what actions should be taken in the face of postoperative troponin elevations, and until a specific treatment or strategy is identified, it is unlikely that patients actually will benefit from routine troponin measurement after noncardiac surgery.

Aspirin noninferior to dalteparin for VTE prophylaxis following hip replacement

Aspirin therapy for 28 days may be a reasonable alternative to low-molecular-weight heparin for extended venous thromboembolism (VTE) prophylaxis among hip replacement patients who have already received low-molecular-weight heparin for 10 days, a study found.

Researchers conducted a multicenter, randomized, controlled trial, the EPCAT (Extended Prophylaxis Comparing Low Molecular Weight Heparin to Aspirin in Total Hip Arthroplasty) study, among 778 patients who had elective, unilateral total hip arthroplasty from 2007 to 2010 at 12 tertiary care orthopedic referral centers in Canada.

After an initial 10 days of dalteparin prophylaxis, patients were randomly assigned to 28 days of dalteparin (n=400) or aspirin (n=386). Researchers noted symptomatic VTE confirmed by objective testing (primary efficacy outcome) and bleeding.

Results appeared in the June 4 Annals of Internal Medicine.

The study was halted prematurely because of decreasing enrollment after a major shift in the use of anticoagulant prophylaxis in Canada following the approval of rivaroxaban. This prompted an unplanned interim analysis by the data safety monitoring board, which found that the primary objective of noninferiority of aspirin had been reached.

Of the enrolled patients, five of 398 (1.3%) randomly assigned to dalteparin and one of 380 (0.3%) randomly assigned to aspirin had VTE (absolute difference, 1.0 percentage point; 95% CI, −0.5 to 2.5 percentage points). Aspirin was noninferior (P<0.001) but not superior (P=0.22) to dalteparin. Clinically significant bleeding occurred in five patients (1.3%) receiving dalteparin and two (0.5%) receiving aspirin. The absolute between-group difference in a composite of all VTE and clinically significant bleeding events was 1.7 percentage points (95% CI, −0.3 to 3.8 percentage points; P=0.091) in favor of aspirin.

The researchers noted that given its low cost and greater convenience, aspirin may be considered a reasonable alternative for extended thromboprophylaxis after total hip arthroplasty. They wrote, “We believe our findings are valid and generalizable, given that the demographic and surgical characteristics were similar between the groups and the study was performed in several centers involving many orthopedic surgeons. The study design reflected clinical practice in that no screening tests for VTE were performed and the primary events were symptomatic ones that caused patients to seek medical attention.”

Rivaroxaban safe, effective for patients with heart failure

Rivaroxaban is a safe, effective choice for patients with heart failure (HF), according to a study.

Previously, the ROCKET AF trial had shown that rivaroxaban was noninferior to warfarin in patients with nonvalvular atrial fibrillation (AF) for preventing stroke and systemic embolic events and reducing intracranial bleeding. Researchers in the current study used data from ROCKET AF to examine whether rivaroxaban was an acceptable alternative to warfarin in HF patients. The primary efficacy outcomes were rates of stroke or systemic embolism by intention to treat, while the secondary safety outcomes were major or nonmajor clinically relevant bleeding and hemorrhagic stroke. The study results were published early online on May 30 by Circulation: Heart Failure.

Overall, 9,033 patients (63.7%) in ROCKET AF had HF at randomization, defined as a history of clinical HF or a left ventricular ejection fraction less than 40%. Those with HF were younger than those without and were more likely to have persistent AF (83.0% vs. 77.6%); they also had higher mean CHADS2 scores (3.7 vs. 3.1). A total of 4,530 patients with HF (50.1%) were randomly assigned to rivaroxaban and 4,503 (49.9%) were randomly assigned to warfarin. Rivaroxaban had similar efficacy to warfarin in patients with HF (1.90 [strokes or systemic embolic events per 100 patient-years] vs. 2.09) and those without (2.10 vs. 2.54; P=0.62 for the interaction). Bleeding risk was also similar with rivaroxaban compared to warfarin in patients with HF (14.22 vs. 14.02) and those without (16.12 vs. 15.35; P=0.99 for the interaction). HF patients taking rivaroxaban had decreased risk for hemorrhagic stroke, and rivaroxaban's efficacy did not appear to differ by HF severity.

The authors noted that patients taking warfarin spent less time in the therapeutic international normalized ratio range than in other studies and that all patients enrolled in the current study were at moderate to high embolic risk. However, they concluded that in this population, rivaroxaban led to similar rates of stroke, systemic embolization and bleeding in patients with and without HF. In addition, no treatment-related differences were observed. “In a clinical environment where the prevalence of both HF and AF are increasing, these data suggest that rivaroxaban is an efficacious and safe alternative to [vitamin K antagonists] in the HF population with AF,” they wrote.

Warfarin better than heparin bridging during cardiac device surgery

For certain high-risk patients undergoing pacemaker or implantable-cardioverter defibrillator surgery, continuing warfarin treatment has lower incidence of device-pocket hematomas than heparin bridging therapy.

Researchers randomized almost 700 Canadian patients who had an annual risk of thromboembolic events of 5% or higher to either continued warfarin treatment through device surgery or bridging therapy with heparin. The primary outcome was device-pocket hematoma that necessitated prolonged hospitalization, interruption of anticoagulation, or further surgery. Results were published in the May 30 New England Journal of Medicine.

Patients in the continued warfarin group had such a significantly lower rate of these hematomas that the trial was terminated after the second prespecified interim analysis (3.5% vs. 16%; relative risk, 0.19; 95% CI, 0.10 to 0.36; P<0.001). The groups had similar rates of surgical and thromboembolic complications, and the warfarin therapy (median international normalized ratio of 2.3) was not associated with any major perioperative bleeding events. The heparin group had one episode of cardiac tamponade and one myocardial infarction, and the warfarin group had one stroke and one transient ischemic attack. Warfarin patients had significantly higher patient satisfaction scores.

On the basis of these results, the study authors concluded that continuation of warfarin may be preferable to bridging therapy for patients and procedures like those included in this trial. The results are not applicable to patients with a risk of thromboembolic events less than 5% or those taking new oral anticoagulants, and the safety of continuing warfarin during other surgical procedures needs to be investigated with randomized, controlled trials, the authors said. They noted that major abdominal, cardiothoracic or neurological surgeries are not likely candidates for experimenting with continuation of warfarin.

The authors also speculated on the cause of their findings, offering the “anticoagulant stress test” theory—that warfarin continuation allows excess bleeding to be observed and managed during surgery, while bridging causes the bleeding to appear only postoperatively when full-dose anticoagulation is resumed.

Anticoagulation likely OK for stroke patients undergoing dental procedures

Stroke patients on blood thinners who undergo dental procedures can routinely continue aspirin or warfarin, according to level A recommendations issued by the American Academy of Neurology.

The available evidence on when to stop blood thinners or resort to bridging medications varies from medication to medication and procedure to procedure, the Academy noted in its recommendations. For certain minor procedures, particularly dental ones, the evidence shows that antithrombotics should not be stopped in most stroke patients.

Recommendations appeared in the May 28 Neurology.

Specifically, the Academy's statement states that patients taking aspirin or warfarin should be counseled that they are highly unlikely to increase clinically important bleeding complications with dental procedures (Level A) and it is reasonable to routinely continue the drugs in stroke patients undergoing dental procedures (Level A).

In addition, doctors can tell patients that aspirin probably does not increase clinically important bleeding complications with invasive ocular anesthesia, cataract surgery, dermatologic procedures, transrectal ultrasound-guided prostate biopsy, spinal/epidural procedures and carpal tunnel surgery (Level B), the recommendations stated. Patients taking aspirin should be counseled that it probably increases bleeding risks during orthopedic hip procedures (Level B, not supportive).

Aspirin might not increase clinically important bleeding in vitreoretinal surgery, electromyography (EMG), transbronchial lung biopsy, colonoscopic polypectomy, upper endoscopy with biopsy, sphincterotomy and abdominal ultrasound-guided biopsies, the statement continued. Because of the weaker data, the recommendations stated that it is reasonable that some stroke patients undergoing these procedures should possibly continue aspirin (Level C). Studies of transurethral resection of the prostate could not exclude clinically important bleeding risks with aspirin (Level U).

Physicians can counsel patients that continuing warfarin is probably associated with a 1.2% increased risk for bleeding during dermatologic procedures, based on a meta-analysis of heterogeneous and conflicting studies (Level B), so patients undergoing dermatologic procedures should probably continue it (Level B). Warfarin might be associated with no increase in clinically important bleeding with EMG, prostate procedures, inguinal herniorrhaphy and endothermal ablation of the great saphenous vein; patients undergoing these procedures should possibly continue warfarin (Level C).

Patients should be counseled that continuing warfarin might increase bleeding with colonoscopic polypectomy (Level C, not supportive) so they should possibly temporarily stop it (Level C). Although warfarin is probably not associated with an increased risk of clinically important bleeding with ocular anesthesia (Level B), anticoagulant practices during ophthalmologic procedures may be driven by the postanesthesia procedure, so there was insufficient evidence to make practice recommendations about stopping it (Level U).

Oxandrolone does not appear to help healing in pressure ulcers

Treatment with the anabolic steroid oxandrolone does not appear to improve healing in patients with pressure ulcers, according to a trial.

Researchers recruited inpatients with spinal cord injuries and severe pressure ulcers at 16 Veterans Affairs Medical Centers to determine whether oxandrolone increased healing compared with placebo and whether ulcers that had healed remained closed eight weeks post-treatment. The parallel-group, placebo-controlled, randomized trial was conducted from Aug. 1, 2005, to Nov. 30, 2008. The study's primary outcome was healed pressure ulcers, and the secondary outcome was pressure ulcers that were still healed at eight-week follow-up. The results were published in the May 21 Annals of Internal Medicine.

Two hundred twelve patients with stage III or stage IV pressure ulcers were randomly assigned to treatment, 108 to the oxandrolone group and 104 to the placebo group. The study drug dosage was 20 mg/d, and treatment lasted for 24 weeks or until the pressure ulcer healed. Healing was seen in 24.1% of pressure ulcers in oxandrolone recipients and 29.8% of pressure ulcers in placebo recipients (difference, −5.7 percentage points; P=0.40). A total of 16.7% of patients in the oxandrolone group and 15.4% of those in the placebo group still had a healed pressure ulcer at week eight (difference, 1.3 percentage points; P=0.70). Although oxandrolone was not associated with any adverse events, elevated liver enzyme levels were noted in 32.4% of the oxandrolone group compared with 2.9% of the placebo group (P<0.001). The study was terminated after three years because a futility analysis determined that detecting a significant between-group difference was unlikely.

The authors acknowledged that only severe wounds were selected for the study, which may have decreased treatment response; that the care provided across centers was not uniform; and that rates of patient withdrawal were high, among other limitations. However, based on their results, they concluded that oxandrolone did not improve pressure ulcer healing compared with placebo, calling into question the practice of using anabolic steroids in patients with pressure ulcers that do not heal.

“Use of an anabolic steroid to increase the healing of nonhealing chronic pressure ulcers in patients with [spinal cord injury] is probably not sufficient to hasten wound closure in the absence of identifying and removing other local or systemic factors that impede the complex process of wound repair,” the authors wrote.

Five-day steroid course effective for acute COPD exacerbations

For inpatients with acute exacerbations of chronic obstructive pulmonary disease (COPD), five days of glucocorticoids is as effective as 14 days at preventing re-exacerbations at six months, a study found.

Researchers studied 314 Swiss patients who presented to the emergency department with acute COPD exacerbation between March 2006 and February 2011. Patients received treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo- controlled manner. In addition to prednisone, all patients received a broad-spectrum antibiotic for seven days and an inhaled, nebulized, short-acting bronchodilator four to six times daily as needed while in the hospital. Additional glucocorticoids could be given at the physician's discretion. The main outcome was time to the next exacerbation, within 180 days.

Results were published online May 21 by the Journal of the American Medical Association.

Ninety-two percent (n=289) of randomized patients were admitted to the hospital; 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis. Estimates of re- exacerbation rates were 37.2% in the short-term treatment group and 38.4% in the longer-term (conventional) treatment group. Time to re-exacerbation did not differ between the groups. There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function. In the conventional group, the mean cumulative prednisone dose was significantly higher (793 mg vs. 379 mg; P<0.001), but treatment-associated adverse reactions, including hyperglycemia and hypertension, occurred with equal frequency. There was a non-significant trend toward fewer instances of hypertension in the short-term group. There also was no difference between groups in the requirement for mechanical ventilation while hospitalized.

The findings support the use of a five-day course of glucocorticoid treatment in acute exacerbations of COPD, rather than the current guidelines for a 10- to 14-day course, the researchers and editorialists concluded. About 10% of patients experience two or more exacerbations yearly, and cumulative exposure to corticosteroids can be substantial and lead to long-term toxicity, including weight gain, diabetes, osteoporosis and fractures. As such, it is important to use the minimal effective dose, the editorialists wrote.