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ITL: Physician Reviews of HM-Relevant Research


In This Edition

Literature At A Glance

A guide to this month’s studies

  1. Neutral head position safe for internal jugular vein cannulation
  2. Thrombolysis decreases mortality in unstable patients with acute PE
  3. Rectal indomethacin decreases incidence of post-ERCP pancreatitis
  4. CHADS2-VASc and HAS-BLED as predictors in afib patients
  5. No readmission, mortality decreases with self-supported COPD management
  6. Medicare Premier P4P initiatives do not decrease mortality
  7. In-hospital rate of DVT/PE after hip and knee arthroplasty
  8. Sodium chloride prevents contrast-induced nephropathy

Neutral Head Position Is Safe for Internal Jugular Vein Cannulation

Clinical question: Is there a difference in the complication rate between neutral head position and 45-degree neck rotation during ultrasound-guided internal jugular vein cannulation?

Background: Cannulation of the internal jugular vein using ultrasound decreases the rate of major complications (carotid artery puncture, pneumothorax, and hemothorax). The relative positions of the internal jugular vein and the carotid artery change based on degree of neck rotation. The optimal position for ultrasound-guided vein puncture has not been shown.

Study design: Prospective, randomized, controlled, non-blinded study.

Setting: Tertiary neurosurgical center in Milan, Italy.

Synopsis: One thousand, three hundred thirty-two patients undergoing major neurosurgical procedures who needed central venous catheter placement were randomized to a neutral head position (NH) or a 45-degree neck rotation (HT) during ultrasound-guided internal jugular vein cannulation. Exclusion criteria were consent refusal, age <12 years, and coagulopathy. Six experienced anesthesiologists performed the procedures; blinding was not possible.

There was no difference in the rate of major complications (carotid artery puncture, pneumothorax, or hemothorax) based on head position (0.9% in NH vs. 0.6% in HT). Minor complications (multiple skin punctures, multiple vein punctures, difficulty inserting the guidewire) were similar in the two groups (13.2% in NG vs. 12.6% in HT). Neck rotation was not associated with operator-reported difficulty or vascular access time.

Limitations of the study include the inability to blind the operator. Additionally, the study involved six experienced anesthesiologists at one center who performed the procedure on patients needing an elective central line. The ability to generalize the findings to other settings, less experienced providers, and patients who need an emergency line is not certain.

Bottom line: Neutral head position is as safe as 45-degree neck rotation for elective ultrasound-guided internal jugular vein cannulation.

Citation: Lamperti M, Subert M, Cortellazzi P, et al. Is a neutral head position safer than 45-degree neck rotation during ultrasound-guided internal jugular vein cannulation? Results of a randomized controlled clinical trial. Anesth Analg. 2012;114:777-784.

Thrombolysis Decreases Mortality in Unstable Patients with Acute Pulmonary Embolism

Clinical question: Does thrombolytic therapy decrease mortality in unstable patients with acute pulmonary embolism (PE)?

Background: PE is a common problem; associated mortality is high. Despite this fact, the data supporting thrombolytic therapy in hemodynamically unstable patients are not robust, and randomized, controlled trials are unlikely to be performed.

Study design: Retrospective cohort study.

Setting: One thousand nonfederal, short-term U.S. hospitals.

Synopsis: Using data from the Nationwide Inpatient Sample database from 1999-2008, investigators found that thrombolysis decreased both all-cause and PE-specific mortality for unstable patients, defined as those either in shock or on a ventilator. Specifically for all-cause mortality, 15% of patients who received thrombolysis died vs. 47% of those who did not (RR 0.31, 95% CI 0.30-0.32). Placement of an inferior vena cava (IVC) filter further reduced mortality, to only 7.6% in patients who received both IVC filter and thrombolysis.

For PE-specific mortality, patients who received thrombolysis also had decreased rates, from 42% to 8.4% (RR 0.20; 95% CI 0.19-0.22). Across all age groups, patients who received thrombolysis had decreased all-cause and PE-specific mortality. Patients who did not receive thrombolysis had additional comorbidities.

As this study is retrospective, it might be affected by unknown confounding. In addition, it relies on coding data to identify patient stability and treatment. Despite this limitation, a randomized, controlled trial is unlikely to be performed at this stage. This study provides evidence to support use of thrombolysis in unstable patients.

Bottom line: Thrombolysis might reduce mortality in unstable patients with acute PE. In combination with IVC filters, the mortality reduction might be even greater.

Citation: Stein PD, Matta F. Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused. Am J Med. 2012;125(5):465-470.

Rectal Indomethacin Decreases Incidence of Post-ERCP Pancreatitis

Clinical question: Does rectal indomethacin reduce the incidence of pancreatitis after ERCP?

Background: Acute pancreatitis is the most common complication from endoscopic retrograde cholangiopancreatography (ERCP). No pharmacologic treatment has proven to reduce the incidence of pancreatitis. Preliminary studies, including a meta-analysis, suggest that the use of NSAIDs might reduce the incidence of post-ERCP pancreatitis.

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

Setting: Multicenter trial at four university-affiliated medical centers in the U.S.

Synopsis: More than 600 patients at high risk for post-ERCP pancreatitis were randomized to receive either two 50-mg indomethacin suppositories or two identical-appearing placebo suppositories. Patients were considered at high risk for pancreatitis based on previously identified patient- and procedure-related risk factors. Most of the participants had sphincter of Oddi dysfunction (84.4% of the indomethacin group and 80.5% of the placebo group). Exclusion criteria included elevated creatinine and active peptic ulcer disease. The indomethacin or placebo suppositories were given immediately following the ERCP.

Post-ERCP pancreatitis, defined by upper abdominal pain, elevation of pancreatic enzymes, and hospitalization for at least two nights, was significantly higher in the placebo group compared with the indomethacin group (16.9% vs. 9.2%, P=0.005). Moderate or severe post-ERCP pancreatitis was significantly higher in the placebo group compared with the indomethacin group (8.8% vs. 4.4%, P=0.03).

There were no significant differences in the rates of clinically significant bleeding or acute renal failure between the two groups. The ability to generalize these findings to patients without risk factors for post-ERCP pancreatitis is not clear.

Bottom line: Rectal indomethacin decreases the rate of post-ERCP pancreatitis in patients who are at high risk for this complication.

Citation: Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. 2012;366(15):1414-1422.

CHADS2-VASc and HAS-BLED Can Predict Thromboembolism and Bleeding Risk in Afib Patients

Clinical question: What are the risk factors for stroke/thromboembolism and bleeding from atrial fibrillation (afib), and how well do the CHADS2-VASc and HAS-BLED stroke and bleeding risk-assessment tools perform against other published stroke and bleeding risk-assessment tools (CHADS2 and HEMORR2HAGES) for patients with afib?

Background: In afib patients, the CHADS2-VASc tool might offer more comprehensive stroke assessment over the CHADS2 by identifying truly-low-risk patients with afib who might not even need antiplatelet therapy. HAS-BLED, a newer bleeding-risk-assessment tool, has been validated in previous trials and is more user-friendly than others. Use of CHADS2-VASc and HAS-BLED are recommended by the European Society of Cardiology to assess stroke and bleeding risks for patients with afib.

Study design: Prospective cohort study.

Setting: All hospitals in Sweden.

Synopsis: Investigators identified 182,678 afib patients via ICD-10 data from Sweden’s National Hospital Discharge Registry ICD-10 from 2005 to 2008. Approximately half the patients were not taking anticoagulants. Analysis assessed risk factors for stroke and bleeding and the performance of CHADS2-VASc and HAS-BLED against CHADS2 and HEMORR2HAGES stroke and bleeding risk-assessment tools.

Risk of composite thromboembolism (unspecified stroke, TIA, systemic embolism) was significantly higher in patients with increased age, peripheral arterial disease, prior myocardial infarction (MI), prior coronary artery bypass grafting (CABG), female gender, renal failure, and aspirin use, as well as hypertension, diabetes, prior thromboembolic event, or prior intracranial hemorrhage (ICH). Interestingly, a statistically increased risk was seen with aspirin use.

Conversely, history of heart failure, thyroid disease, and obesity were not associated with increased composite thromboembolic risk. The use of CHADS2-VASc was marginally better than CHADS2 in predicting stroke risk.

ICH risk was increased in patients with older age, prior ischemic stroke, prior ICH, and hypertension. Risk of composite bleeding (from ICH or other major bleeding) was significantly higher in patients with these risk factors, as well as renal failure, liver disease, anemia, dysfunctional platelets, alcohol use, and cancer. Ischemic heart disease was associated with a statistically significant lower risk of ICH, but not of composite bleeding risk.

HAS-BLED usage was as good as, and easier to use than, HEMORR2HAGES in predicting bleeding risk.

Bottom line: CHADS2-VASc might be better than CHADS2 in predicting truly-low-risk patients with nonvalvular afib; HAS-BLED is just as good as, and easier to use than, HEMORR2HAGES in predicting bleeding risk for patients with nonvalvular afib who are to receive antithrombotic therapy.

Citation: Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182,678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33(12):1500-10 [Epub 2012 Jan 13].

Supported Self-Management of COPD Does Not Decrease Readmission or Mortality Rates

Clinical question: Does supported self-management of patients with chronic obstructive pulmonary disease (COPD) decrease COPD-related hospital readmission or death?

Clinical background: Supported self-management has benefited patients with such chronic diseases as heart failure and asthma. Evidence to support such a strategy for patients with COPD is relatively lacking.

Study design: Randomized, controlled trial.

Setting: Community-based care following urban hospitalization in western Scotland.

Synopsis: From June 2007 to May 2009, and following hospitalization for COPD exacerbation, 464 patients were randomized to receive routine community-based care with or without 12 months of support and training to detect, and promptly treat, recurrent exacerbations. Independent of disease severity or demographics, investigators found no difference in combined readmission (48% vs. 47%, 95% confidence interval [CI] 0.80-1.38) or death (10% vs. 7%, 95% CI 0.71-2.61).

Based on review of appropriateness of self-management strategies used by the intervention group, unplanned exploratory subgroup analysis classified a minority of the intervention group as “successful” (42%) supported self-managers, and demonstrated decreased COPD readmissions and death (27% vs. 49%, 95% CI 0.25-0.76, P=0.003) vs. “unsuccessful” self-managers. This successful group was younger and tended to live with others. Further research to define characteristics of patients who benefit from self-management is needed.

Bottom line: Supported self-management of COPD does not reduce COPD-related readmission or death in a large population.

Citation: Bucknall CE, Miller G, Lloyd SM, et al. Glasgow supported self-management trial (GSuST) for patients with moderate to severe COPD: randomised controlled trial. BMJ. 2012;344:e1060 [Epub ahead of print].

Medicare Premier P4P Initiatives Do Not Decrease Mortality

Clinical question: Has the Medicare Premier Hospital Quality Incentive Demonstration (HQID) resulted in lower mortality?

Background: The Centers for Medicare & Medicaid Services’ (CMS) value-based purchasing program will expand to include 30-day mortality in 2013, but do pay-for-performance (P4P) initiatives result in improved mortality? Studies have demonstrated improvement in process of care but have not demonstrated mortality benefit thus far.

Study design: Cohort study.

Setting: Two hundred fifty-two hospitals participating in the Premier HQID compared with 3,363 control hospitals participating in the Hospital Compare program.

Synopsis: Researchers examined 30-day mortality for patients admitted with acute myocardial infarction, congestive heart failure, pneumonia, and for coronary artery bypass grafting (CABG) from 2003 to 2009. Results showed no difference in 30-day mortality rates over the six-year span of the program for any of the conditions studied in the Premier hospitals (participating in the voluntary pay-for-performance program) vs. non-Premier hospitals (11.82% vs. 11.74%). This held true for each condition measured individually, with a higher mortality rate for patients undergoing CABG at the Premier hospitals.

In addition, in the hospitals that underperformed initially, there was no difference with respect to rate of improvement when comparing Premier vs. non-Premier hospitals. Furthermore, mortality rate trends did not differ between those conditions that were incentivized (acute MI and CABG) compared with those that were not (congestive heart failure and pneumonia).

The authors concluded that there was “little evidence” that the Premier HQID pay-for-performance program resulted in reduced 30-day mortality.

Bottom line: Programs participating in the Medicare Premier HQID pay-for-performance program had similar 30-day mortality compared with nonparticipating programs.

Citation: Jha AK, Joynt KE, Orav EJ, Epstein AM. The long-term effect of premier pay for performance on patient outcomes. N Engl J Med. 2012;366:1606-1615.

In-Hospital Rate of DVT/PE After Hip and Knee Arthroplasty with Guideline-Recommended Prophylaxis

Clinical question: What is the rate of symptomatic DVT/PE after total or partial hip (TPHA) or knee (TPKA) arthroplasty using currently recommended prophylaxis?

Background: The rate of postoperative DVT/PE after TPHA/TPKA has dropped dramatically with use of pharmacologic prophylaxis. However, the current rate of symptomatic DVT/PE using current pharmacologic prophylaxis is not known. Such rates are needed for informed patient consent and development of patient safety benchmarks.

Study design: Systematic review.

Setting: Randomized clinical trials (RCTs) and observational studies worldwide of adult inpatients undergoing TPHA and/or TPKA from 1996 to 2011.

Synopsis: Forty-seven studies were included, of which 41 were RCTs and six were observational studies. Twenty-one studies evaluated rates after TPHA, 20 after TPKA, and six after both. More than 44,000 patients were included, with ages ranging from 58 to 74 years. The mean duration of prophylaxis was eight days, with a mean follow-up of 13 days.

In-hospital rates of symptomatic venous thromboembolism (VTE) were higher in patients undergoing TPKA than TPHA (1.09% vs. 0.53% for VTE, 0.63% vs. 0.26% for DVT, and 0.27% vs. 0.14% for PE). This is in contrast to the higher rates of VTE observed after TPHA when the post-discharge period is included. The pooled incidence of VTE was lower with use of direct inhibitors of Factors Xa or IIa when compared to low-molecular-weight heparin, although a direct efficacy comparison could not be made.

Because the majority of studies were RCTs with restrictive inclusion criteria, rates of DVT/PE in actual practice might be higher.

Bottom line: When informing patients of postoperative VTE risk, or establishing benchmarks to evaluate patient safety, one can anticipate an in-hospital VTE rate of 0.5% following TPHA and 1% following TPKA.

Citation: Januel JM, Chen G, Ruffieux C, et al. Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip and knee arthroplasty among patients receiving recommended prophylaxis: a systematic review. JAMA. 2012;307(3):294-303.

Sodium Chloride Prevents Contrast-Induced Nephropathy

Clinical question: Is sodium chloride more effective than sodium bicarbonate for preventing contrast-induced nephropathy?

Background: Contrast-induced nephropathy can be prevented with precontrast hydration. Study authors sought to compare sodium chloride administered over 24 hours with sodium bicarbonate administered over seven hours, and with sodium bicarbonate administered orally.

Study design: Randomized, open-label, controlled trial.

Setting: Three European medical centers.

Synopsis: The study examined 258 patients with an estimated glomerular filtration rate <60mL/min/1.73m2 undergoing intravenous or intra-arterial contrast procedure. Patients with Class III or IV heart failure were excluded. The remaining patients were randomized to receive one of three regimens: sodium chloride at 1 ml/kg/hr for 12 hours prior to and 12 hours following the procedure; intravenous sodium bicarbonate for one hour prior to and six hours following the procedure; or intravenous and oral sodium bicarbonate 20 minutes prior to the procedure.

The group that received saline had a lower incidence of contrast-induced nephropathy than the bicarbonate groups (1% vs. 9% vs. 10%). The oral bicarbonate strategy was noninferior to the seven-hour intravenous bicarbonate strategy.

The authors postulated that saline should be used for high-risk patients, but that given the overall low incidence of contrast-induced nephropathy, the short-term bicarbonate strategy (intravenous followed by oral) is a viable alternative for low-risk patients.

Bottom line: Sodium chloride is more effective than sodium bicarbonate for preventing contrast-induced nephropathy, but in light of the low incidence, a short course of sodium bicarbonate is a possible convenient alternative for low-risk patients.

Citation: Klima T, Christ A, Marana I, et al. Sodium chloride vs. sodium bicarbonate for the prevention of contrast medium-induced nephropathy: a randomized controlled trial. Eur Heart J. 2012 Jan 19 [Epub ahead of print].

Clinical Shorts


In high-risk patients with elevated bilirubin or BUN and diagnosed with SBP, albumin infusion might improve mortality but is not necessary in low-risk patients.

Citation: Poca M, Concepción M, Casas M, et al. Role of albumin treatment in patients with spontaneous bacterial peritonitis. Clin Gastroenterol Hepatol. 2012;10:309-315.


An observational population-based cohort study in Ontario revealed that elderly patients prescribed fibrates were more likely to be hospitalized for increased serum creatinine and undergo nephrology consultation than those prescribed ezetimibe.

Citation: Zhao YY, Weir MA, Manno M, et. al. New fibrate use and acute renal outcomes in elderly adults: a population-based study. Ann Intern Med. 2012;156(8):560-569.

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