Patient Care

In the Literature: HM-Related Research You Need to Know


In This Edition

Literature at a Glance

A guide to this month’s studies

Clinical Shorts


Pooled analysis of 10 randomized trials showed oral anticoagulation with or without aspirin does not reduce mortality or reinfarction, and it reduces stroke but is associated with significantly more major bleeding.

Citation: Haq SA, Heitner JF, Sacchi TJ, Brener SJ. Long-term effect of chronic oral anticoagulation with warfarin after acute myocardial infarction. Am J Med. 2010;123(3):250-258.


Observational study revealed that junior neurointensivists are better in predicting poor outcomes than good outcomes at six months in neurologic patients requiring mechanical ventilation for ≥72 hours.

Citation: Caulfield AF, Gabler L, Lansberg MG, et al. Outcome prediction in mechanically ventilated neurologic patients by junior neurointensivists. Neurology. 2010;74:1096-1101.

Arterial and Central Venous Catheters Have Similar Rates of Colonization and Blood Stream Infections

Clinical question: Are arterial catheters (ACs) safer than central venous catheters (CVCs) in terms of colonization and catheter-related infections?

Background: Unlike CVCs, only a few studies have addressed blood-stream infections (BSI) related to AC usage, probably due to the traditional perception that ACs pose a lesser risk of colonization and BSI than CVC.

Study design: Randomized, controlled trial.

Setting: Three university hospitals and two general hospitals in France.

Synopsis: The study included 3,532 catheters (1,915 CVC and 1,617 AC) with 27,541 catheter-days from seven ICU settings. The same standard procedures were followed for catheter insertion and site dressing change at the various centers. Catheters were removed when they no longer were needed or when catheter-related infection (CRI) was suspected.

Colonization and CRI rates were similar in both arterial and venous catheters: 7.9% vs. 9.6% and 0.68% vs. 0.94%, respectively. The daily risk of colonization over time was stable for CVC, but appeared to increase for AC.

One important limitation to this study is that many patients had both arterial and venous catheters, leading to difficulty attributing infection to either one. Hospitalists caring for ICU patients should weigh the risks and benefits of prolonged use of AC due to similar rates of colonization and CRI as CVC.

Bottom line: Arterial and central venous catheters are equally prone to colonization and cause similar rates of CRI, but AC daily risk tends to increase with time; thus, AC should receive the same precautions as CVC.

Citation: Lucet JC, Bouadma L, Zahar JR, et. al. Infectious risk associated with arterial catheters compared with central venous catheters. Crit Care Med. 2010;38(4):1030-1005.

Rifaximin Prevents Recurrence of Hepatic Encephalopathy Episodes and Reduces Associated Risk for Hospitalization

Clinical question: What is the efficacy of rifaximin for the prevention of hepatic encephalopathy?

Background: Hepatic encephalopathy is a chronic, debilitating complication of liver cirrhosis. The efficacy of treatment of acute episodes with rifaximin is well documented in the literature; however, prevention of such episodes using rifaximin is poorly studied.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Seventy centers in the U.S., Canada, and Russia.

Synopsis: A total of 299 chronic liver disease patients, in remission from recurrent hepatic encephalopathy, randomly were assigned to receive either oral rifaximin (140 patients) or placebo (159 patients) for six months.

When compared to placebo, rifaximin reduced the risk of breakthrough episodes of hepatic encephalopathy over a six-month treatment period (22.1% vs 45.9%, HR 0.42; 95% confidence interval, 0.28-0.64, P<0.001), as well as risk of hospitalization involving hepatic encephalopathy (13.6% vs 22.6%, HR 0.50; 95% CI, 0.29-0.87, P=0.01).

The incidence of adverse effects was similar in both groups. More than 90% of patients received concomitant lactulose therapy.

Bottom line: Rifaximin treatment delays the first breakthrough episode of hepatic encephalopathy during a six-month period; moreover, it significantly reduces the associated risk for hospitalization.

Citation: Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362:1071-1081.

Clinical Shorts


Epidemiological data indicate that aerosolization of C. diff occurs commonly but sporadically in patients with symptomatic C. diff infection—and it is prudent to have single-room isolation to limit its spread.

Citation: Best EL, Fawley WN, Parnell P, Wilcox MH. The potential for airborne dispersal of Clostridium difficile from symptomatic patients. CID. 2010;50(11):1450-1457.


Matched, case-control study shows that ≥2 years use of PPIs and H2-receptor antagonist was associated with 30% and 18% higher risk of hip fracture, respectively.

Citation: Corley DA, Kubo A, Zhao W, et al. Proton pump inhibitor and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology. 2010;139:93-96.

Early Tracheotomy Does Not Decrease the Incidence of Ventilator-Associated Pneumonia in ICU Patients

Clinical question: Does early tracheotomy decrease the incidence of ventilator-associated pneumonia (VAP) in mechanically ventilated adult ICU patients without existing lung infection?

Background: There is considerable variation in timing and incidence of tracheotomy across ICUs. Observational studies have reported that tracheotomy performed earlier might be associated with quicker weaning from mechanical ventilation; however, randomized, controlled trials have failed to confirm this finding.

Study design: Multicenter randomized controlled trial.

Setting: Adult ICU in Italy.

Synopsis: Between 2004 and 2008, 600 mechanically ventilated patients without lung infection were enrolled from 12 adult ICUs in Italy. Of these patients, 419 were randomized to early tracheotomy performed six to eight days after intubation (N=209) or to late tracheotomy performed 13-15 days after intubation (N=210).

VAP was diagnosed in 14% of patients in the early tracheotomy group, compared with 21% in the late tracheotomy group (P=0.07). Although the number of ventilator-free and ICU-free days was higher in the early tracheotomy group, long-term outcomes did not differ between the two groups.

Only 69% of patients in the early tracheotomy group and 57% of patients in the late tracheotomy group received tracheotomy, but all the patients were included in the final analysis due to the intention-to-treat design of the study, which might have diluted the effect of the intervention. In addition, the smaller sample size may have prevented the study from reaching statistical significance.

Bottom line: Early tracheotomy does not significantly decrease the incidence of VAP as compared to late tracheotomy.

Citation: Terragni PP, Antonelli M, Fumagalli R, et al. Early vs. late tracheotomy for prevention of pneumonia in mechanically ventilated adult ICU patients. JAMA. 2010;303(15): 1483-1489.

Coagulopathy in Cirrhotic Patients Is Not Protective against VTE

Clinical question: Does the degree of INR elevation affect the incidence of VTE in hospitalized patients with cirrhosis?

Background: Chronic liver disease (CLD) and subsequent development of cirrhosis renders patients coagulopathic. Historically, this has provided a sense of security to clinicians that these patients inherently possess a decreased VTE risk.

Study design: Retrospective cohort study.

Setting: University of Missouri Medical Center in Columbia.

Synopsis: Chart review of patients admitted with CLD and cirrhosis from Jan. 1, 2000, and Jan. 31, 2007, demonstrated an incidence rate of VTE of 6.3%, which is much higher than previous reports.

Most patients with CLD received no thrombosis prophylaxis; notably, there was no difference in VTE incidence between subgroups who received prophylaxis and those who did not. Five percent of VTE cases occurred in patients with an INR exceeding 1.6, with Child-Pugh class C patients having the highest thromboembolism incidence.

This retrospective chart review was limited by information and reporting bias and the inability to control confounding variables. Less than half of the patients were screened for VTE, which means that the true incidence of thrombus could actually be higher. Further studies are needed to provide proper risk assessment.

Bottom line: Patients with CLD and cirrhosis are at risk for VTE, even in the setting of coagulopathy, and might require VTE prophylaxis.

Citation: Dabbagh O, Oza A, Prakash S, Sunna R, Saettele TM. Coagulopathy does not protect against venous thromboembolism in hospitalized patients with chronic liver disease. Chest. 2010;137(5):1145-1149.

Clinical Shorts


Randomized, placebo-controlled, double-blind trial showed that patients with advanced cirrhosis experienced fewer complications at two and six months while on pentoxifylline therapy, without decrease in short-term mortality.

Citation: Lebrec D, Thabut D, Oberti F, et al. Pentoxifylline does not decrease short-term mortality but does reduce complications in patients with advanced cirrhosis. Gastroenterology. 2010;138:1755-1762.

Pulmonary Embolism Can Be Safely Excluded Using Age-Adjusted D-dimer Cut-off Value

Clinical question: Does the new age-adjusted D-dimer cutoff value in older patients safely exclude pulmonary embolism (PE)?

Background: D-dimer is a useful blood test to exclude PE; however, D-dimer concentration increases with age, and hence the current cutoff of 500µg/l used in excluding a PE becomes less specific in older patients.

Study design: Retrospective multicenter cohort study.

Setting: General and teaching hospitals in Belgium, Switzerland, France, and Netherlands.

Synopsis: The study included 5,132 consecutive patients with clinically suspected PE. Patients were distributed into a derivation set (N=1,331) and two independent validation sets (N1=2,151 and N2=1,643). For patients older than 50, the use of the new age-adjusted D-dimer cutoff (patient age multiplied by 10µg/l) resulted in a combined 11% increase in the number of patients with negative results. This increase was more prominent in patients aged older than 70 (13% to 16%).

The new age-adjusted D-dimer cutoff point failed to detect PE in 0.2% of cases in the derivation set and in 0.6% and 0.3% of cases in the two validation sets, respectively. However, despite external validation, prospective studies are needed before implementing such criteria into clinical practice.

Bottom line: The age-adjusted D-dimer combined with clinical probability greatly increases the proportion of older patients in whom PE can be safely excluded.

Citation: Douma RA, Le Gal G, Söhne M, et al. Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts. BMJ. 2010;340:c1475.

Antihypertensive Drugs After Stroke Does Not Impact Cardiovascular Event Rate or Mortality at Six Months

Clinical question: Should antihypertensive medications be continued during the immediate post-stroke period in patients who previously were on such therapy?

Background: More than 50% of patients suffering from acute stroke are on antihypertensive therapy prior to admission. However, efficacy of such therapy in reducing cardiovascular event rates and mortality in the immediate post-stroke period is not well studied.

Study design: Prospective, randomized, open-blinded-endpoint trial.

Setting: Forty-nine UK National Institute for Health Research Stroke Centers.

Synopsis: From January 2003 and March 2009, 763 patients with pre-existing hypertension and diagnosis of mild to moderate acute stroke were recruited and assigned to continue or stop antihypertension drugs. The time limit for inclusion into the study was within 48 hours of the stroke and the endpoint was death or dependency (modified Rankin Scale >3) at the end of two weeks.

There was a statistically significant difference in the two groups at two weeks in both systolic and diastolic pressures, 13 mmHg and 8mmHg, respectively (P<0.0001). Seventy-two of 379 patients in the continuation group and 82 of 384 patients in the stop group reached the primary endpoint (P=0.3). The latter point is a major limitation to this trial, since it was underpowered because of early termination to detect differences in outcomes.

Bottom line: Antihypertensive therapy during the immediate post-stroke period did not reduce two-week death or dependency, cardiovascular event rate, or mortality at six months.

Citation: Robinson TG, Potter JF, Ford GA, et al. Effects of antihypertensive treatment after acute stroke in the continue or stop post-stroke antihypertensives collaborative study (COSSACS): a prospective, randomized, open, blinded-endpoint trial. Lancet Neurol. 2010;9:767-775.

Clinical Shorts


Retrospective study demonstrated no effect of prolonged preoperative steroid therapy on intraoperative blood transfusion or postoperative thromboembolic complications in noncardiac surgical patients; however, authors noted a 24% and 21% increased risk of systemic and wound infections, respectively.

Citation: Turan A, Dalton JE, Turner PL, Sessler DI, Kurz A, Saager L. Preoperative prolonged steroid use is not associated with intraoperative blood transfusion in noncardiac surgical patients. Anesthesiology. 2010;113:285-291.

All Lumens from Multi-Lumen Catheters Should Be Cultured to Diagnose Catheter-Related Bloodstream Infections

Clinical question: Do all lumens from multi-lumen catheters need to be cultured to best diagnose catheter-related bloodstream infections (CRBSIs)?

Background: The recent Infectious Diseases Society of America’s “Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infections” has not conclusively established the number of lumens to culture from multi-lumen catheters when attempting to diagnose CRBSIs.

Study design: Retrospective cohort study.

Setting: Large teaching institution in Spain.

Synopsis: From January 2003 until May 2009, 154 patients, mostly men, with a mean age of 58.1 years, were recruited to participate in the study. Of these, 171 episodes of proven CRBSIs were detected in 154 subjects. Of the 171 tested catheters (112 double lumen and 59 triple lumen), testing only one lumen from double catheters would have led to 27.2% of missed cases for CRBSIs. Additionally, testing only two or one lumen from triple lumen catheters would have led to 15.8% and 37.3% of missed cases for CRBSIs, respectively.

The study was limited by being conducted at a single test site and the need to withdraw catheters to perform endoluminal brushing and semi-quantitative techniques. Though diagnostic yield might significantly improve by culturing all multi-lumen sites, hospitalists should consider the time and cost expenditure for testing from more than one lumen.

Bottom line: Culturing all lumens from multi-lumen catheters could greatly increase diagnostic yield in CRBSIs.

Citation: Guembe M, Rodríguez-Créixems M, Sánchez-Carrillo C, Pérez-Parra A, Martín-Rabadán P, Bouza E. How many lumens should be cultured in the conservative diagnosis of catheter-related bloodstream infections? CID. 2010;50(12):1575-1579.

Early Anticoagulation Improves Survival after Acute PE

Clinical question: Does the timing of initial heparinization reduce mortality in patients with acute symptomatic PE?

Background: Acute PE is rapidly fatal if not diagnosed and treated. Studies have shown that intravenous heparin improves overall survival for patients with PE, and therapeutic anticoagulation reduces rates of recurrent VTE. However, studies investigating the relation between time to achieve therapeutic anticoagulation and mortality or PE recurrence are limited.

Study design: Retrospective cohort study.

Setting: Mayo Clinic, Rochester, Minn.

Synopsis: From June 2002 and September 2005, 400 patients were identified with PE using retrospective data from Mayo Clinic’s electronic medical records. Patients who received heparin in the ED had lower in-hospital mortality (OR 0.20, 95% CI, 0.06-0.69) and 30-day mortality (OR 0.25, 95% CI, 0.12-0.55) compared with patients who received heparin after admission. Similarly, patients who achieved a therapeutic aPTT within 24 hours also had lower 30-day mortality (OR 0.34, 95% CI, 0.14-0.84). Patients with COPD and malignancies had higher in-hospital and 30-day mortality, respectively.

Bottom line: It is difficult to draw a causal relationship from a retrospective review, but hospitalists should start immediate anticoagulation therapy when a PE is suspected.

Citation: Smith SB, Geske JB, Maguire JM, Zane NA, Carter RE, Morgenthaler TI. Early anticoagulation is associated with reduced mortality for acute pulmonary embolism. Chest. 2010;137(6): 1382-1390. TH


Ibuprofen Use Associated with Complicated Pneumonia

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: What baseline characteristics are associated with suppurative complications in children hospitalized with community-acquired pneumonia?

Background: The prevalence of suppurative complications of community-acquired pneumonia (CAP) appears to be on the rise. Reasons for this increase remain unclear, although etiologic organism, older age, prior antibiotic, and nonsteroidal anti-inflammatory drug use have been implicated in a single prior retrospective study.

Study design: Retrospective cohort study.

Setting: Two hospitals in France.

Synopsis: Two physicians reviewed 1,184 charts based on ICD-10 discharge codes for pneumonia from 1995 to 2003. Children younger than 28 days and older than 15 years were excluded. Additionally, children with underlying or cardiorespiratory pathology were excluded. After applying predefined clinical criteria for pneumonia and suppurative complications, 677 children with CAP were compared to 90 with suppurative complications of pneumonia.

The incidence of suppurative complications increased to 13 per 100,000 from 0.5 per 100,000 over the time period. A minority of patients had etiologic microbes isolated, primarily Streptococcus pneumoniae, in both groups. Complicated pneumonia was more frequently seen in older children, and in children with prior antibiotic and anti-inflammatory medication use. After multivariable analysis, only ibuprofen use remained with an increased odds ratio (2.57, 95% confidence interval, 1.51-4.35) of complicated pneumonia.

The clear drawback of this study is an inability to draw a causal connection between ibuprofen use and the development of suppurative complications of pneumonia. The retrospective nature of the analysis further limits hypothesis generation. Nevertheless, it is notable that the results corroborate findings from a prior study in the U.S., in which ibuprofen was found to significantly increase the likelihood of parapneumonic empyema.

Bottom line: Ibuprofen use is associated with the development of suppurative complications of pneumonia.

Citation: François P, Desrumaux A, Cans C, Pin I, Pavese P, Labarère J. Prevalence and risk factors of suppurative complications in children with pneumonia. Acta Paediatr. 2010;99(6):861-866.

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