ITL: Physician Reviews of HM-Relevant Research


In This Edition

Literature At A Glance

A guide to this month’s studies

  1. Acute myocardial infarction risk after hip/knee surgery
  2. Preoperative alcohol cessation minimizes complications in elective surgery
  3. Early laparoscopic cholecystectomy for gallstone pancreatitis
  4. Low-dose steroids in shock patients
  5. Pharmacist intervention did not reduce post-discharge errors
  6. Hyperbaric oxygen therapy and necrotizing soft-tissue infections
  7. Worse stroke outcomes on weekends
  8. Hospital admissions from EDs increasing
  9. Avoiding intensive glucose control in acute stroke
  10. Peri-procedural bleeding with dabigatran versus warfarin

Increased Risk of Acute Myocardial Infarction after Hip/Knee Surgery

Clinical question: How long does the risk of acute myocardial infarction (AMI) last after hip or knee replacement surgery, and what factors affect the risk?

Background: AMI is a morbid, perioperative complication of hip/knee surgery. Previous studies have demonstrated an increased risk of AMI post-surgery; however, this is the first study to assess the timing and modifiers of the risk.

Study design: Retrospective cohort study.

Setting: Data from Danish national registries from 1998 to 2007.

Synopsis: All adult patients who received total hip replacement (THR, n=66,524) or total knee replacement (TKR, n=28,703) surgery, as identified by hospital discharge records during a 10-year period, were matched with three age/sex controls without a history of THR or TKR (n=286,165). Patients with prior AMI within six weeks of the index date were excluded (n=437). The patients were followed until death, THR or TKR revision, migration, or the end of the study period.

Thromboprophylaxis was received by 99.1% of THR and TKR patients. The risk of AMI was significantly elevated for two weeks in TKR patients, and for six weeks in THR patients. Age >60 significantly increased the risk of AMI for both study populations. The risk associated with a previous AMI before THR or TKR diminished with increasing time between the two events.

The study was limited by lack of controlling for some AMI risk factors, such as smoking history or BMI.

Bottom line: AMI risk is substantially elevated for six weeks after THR and for two weeks after TKR. Preoperative risk factors to consider include age >60 and AMI within a year.

Citation: Lalmohamed A, Vestergaard P, Klop C, et al. Timing of acute myocardial infarction in patients undergoing total hip or knee replacement. Arch Intern Med. 2012;172:1229-1235.

Preoperative Alcohol Cessation Minimizes Complications of Elective Surgery in Heavy Alcohol Users

Clinical question: Does preoperative alcohol cessation minimize complication rates, mortality, or length of stay (LOS) in heavy alcohol users?

Background: Alcohol abuse is prevalent worldwide and contributes to 1.8 million deaths per year. Heavy alcohol users have an increased risk of postoperative bleeding, cardiopulmonary complications, and infections. It is unknown if preoperative cessation can reduce the risk of postoperative complications.

Study design: Systematic review.

Setting: Two Danish randomized controlled trials.

Synopsis: A Cochrane review identified 671 potential studies, of which 655 were excluded after abstract review. Of the 16 studies remaining, 14 were not randomized controlled trials with preoperative intervention for alcohol cessation. In the two studies that remained (n=69), patients who received preoperative alcohol cessation had fewer postoperative complications (odds ratio=0.22, 95% CI 0.08-0.61, P=0.004). Interventions included disulfiram and medical supervision of alcohol cessation. Investigators found no significant reductions for in-hospital or 30-day mortality.

Limitations of this review include lack of blinding to the treatments, low numbers of included women, and both studies being conducted by the same author.

Bottom line: Heavy alcohol users might benefit from a preoperative alcohol cessation program, but further studies are needed.

Citation: Oppedal K, Moller AM, Pedersen B, Tonnesen H. Preoperative alcohol cessation prior to elective surgery. Cochrane Database Syst Rev. 2012;7:CD008343.

Early Laparoscopic Cholecystectomy Is Safe and Effective for Gallstone Pancreatitis

Clinical question: Does early laparoscopic cholecystectomy (<48 hours of admission) in mild gallstone pancreatitis decrease LOS without increasing morbidity and mortality?

Background: Time to laparoscopic cholecystectomy (LC) for mild gallstone pancreatitis is greatly debated. Historically, surgeons have waited for normalization of laboratory values and decreased symptoms before performing laparoscopic or open cholecystectomy. Two previous studies demonstrated LC can be performed safely within 48 hours of admission, regardless of symptoms or laboratory values.

Study design: Retrospective cohort.

Setting: Two academic medical centers in California.

Synopsis: This retrospective review of 303 patients who underwent LC for mild gallstone pancreatitis from 2006 to 2011 found 117 (38.6%) underwent early LC and 186 (61.4%) underwent delayed LC (>48 hours after presentation). No significant differences in patient demographics, laboratory values, or admission Ranson scores were found between the groups. The mean LOS was significantly shorter in the early LC group (3.4 days) compared with the delayed LC group (6.3 days), and the delayed LC group had a higher rate of preoperative endoscopic retrograde cholangiopancreatography (ERCP). No differences were found with regard to mortality, complication rates, 30-day readmissions, or conversion to open cholecystectomy.

This study is limited by its retrospective design and potential for uncontrolled confounders. In addition, it did not evaluate preoperative management, postoperative recovery time, or timing of surgical consultation, which could have affected outcomes between the groups. It also is difficult to predict mild gallstone pancreatitis on admission, as some of the Ranson criteria should be calculated at 48 hours, and 5% to 10% of mild gallstone pancreatitis will progress to severe pancreatitis.

Bottom line: Early laparoscopic cholecystectomy (<48 hours of presentation) in mild gallstone pancreatitis is associated with shorter LOS and decreased ERCP use, with no difference in morbidity or mortality.

Citation: Faylor AE, de Virgilio C, Stabile BE, et al. Early laparoscopic cholecystectomy for mild gallstone pancreatitis. Time for a paradigm shift. Arch Surg. 2012;16:1-5.

Low-Dose Steroids in Shock Patients

Clinical question: Do low-dose corticosteroids improve mortality or shock reversal in adults with septic shock?

Background: Several trials have been published to evaluate the efficacy of low-dose corticosteroids in septic shock.

Study design: Systemic review and meta-analysis of randomized controlled trials.

Setting: Not identified.

Synopsis: Seven randomized controlled trials that utilized low-dose corticosteroids and reported either mortality or time-to-shock reversal in adults with septic shock were included in this review. Shock reversal was not consistently defined across trials but included time to withdrawal of vasopressors, proportion of patients on vasopressors on Day 3, or stable systolic blood pressure of >90 mm Hg for at least 24 hours without vasopressor support.

Pooled results found a significant improvement in shock reversal after low-dose corticosteroid administration (300 mg hydrocortisone in 24 hours [relative risk=1.17, 95% CI, 1.07-1.28]). Pooled results from six studies (n=965) did not find a significant difference in

mortality among those receiving low-dose corticosteroids.

Of note, two of the seven studies represented a disproportionate number of included patients, and the search only included the MEDLINE database, so some randomized controlled trials might have been missed.

Bottom line: Low-dose corticosteroids might reverse shock faster, but they do not improve mortality.

Citation: Sherwin RL, Garcia AJ, Bilkovski R. Do low-dose corticosteroids improve mortality or shock reversal in patients with septic shock? A systemic review and position statement prepared for the American Academy of Emergency Medicine. J Emerg Med. 2012;43:7-12.

Pharmacist Intervention Did Not Reduce Medication Errors after Discharge

Clinical question: Does pharmacist intervention reduce clinically important medication errors after hospital discharge for patients with acute coronary syndrome (ACS) or decompensated congestive heart failure?

Background: Research has shown adverse drug events, including discrepancies in medication regimens and nonadherence, affect 11% to 17% of discharged patients. Pharmacist interventions reduce medication errors in hospitalized patients, but their impact on recently discharged patients is unknown.

Study design: Blinded randomized controlled trial.

Setting: Two U.S. tertiary-care academic hospitals.

Synopsis: Investigators randomized 851 patients admitted with ACS or decompensated heart failure to receive pharmacist intervention or usual care. The intervention involved pharmacist medication reconciliation (“med rec”), inpatient pharmacist counseling, low-literacy adherence aids, and post-discharge follow-up phone calls.

The primary outcome of clinically important medication errors within 30 days of discharge occurred in 50.8% of all patients. The intervention and usual-care groups had similar mean number of errors, 0.87 and 0.92 events per patient, respectively. Results by intention-to-treat analysis favored the intervention but did not meet statistical significance (adjusted RR 0.92, CI 0.77-1.09).

Both hospitals had sufficient resources to support med rec and electronic health records. The study population was well-educated, with only a 10% prevalence of inadequate health literacy, compared with 26% noted in prior literature. These factors could help explain the study’s negative findings.

Study limitations include whether the results are generalizable to other settings or noncardiac populations. Further study is needed to determine characteristics of patients and settings that could benefit from pharmacist involvement to decrease medication errors.

Bottom line: A pharmacist intervention did not reduce medication errors in cardiac patients after discharge.

Citation: Kripalani S, Roumie CL, Dalal AK, et al. Effect of a pharmacist intervention on clinically important medication errors after hospital discharge. Ann Int Med. 2012;157:1-10.

Hyperbaric Oxygen Therapy Saves Lives in Necrotizing Soft-Tissue Infections

Clinical question: Is the use of hyperbaric oxygen therapy in necrotizing soft-tissue infections (NSTIs) effective in improving patient outcomes?

Background: Studies evaluating the benefits of hyperbaric oxygen therapy (HBO2 therapy) in NSTIs are limited. The mainstay of management remains early surgical debridement and antibiotics. Given the significant risk of mortality and long-term disability from limb and tissue loss, alternative treatments need to be considered.

Study design: Retrospective analysis.

Setting: The Nationwide Inpatient Sample (NIS) database.

Synopsis: This study evaluated 45,913 patients in the NIS from 1988 to 2009, of which 405 patients received HBO2 therapy. Overall, those receiving HBO2 therapy had a lower mortality rate (4.5% vs. 9.4%). After adjusting for predictors and confounders, those receiving HBO2 therapy had a statistically significant lower risk of mortality, but they did have higher hospital costs and longer LOS.

The NIS database does not capture several predictors and confounders for NSTI patients. Additionally, the lack of data regarding the number of HBO2 therapy sessions received makes it impossible to estimate a dose response.

Bottom line: This retrospective analysis of NSTI patients found HBO2 therapy was associated with significantly lower mortality but higher hospitalization cost and longer LOS.

Citation: Soh CR, Pietrobon R, Freiberger JJ, et al. Hyperbaric oxygen therapy in necrotizing soft tissue infections: a study of patients in the United States Nationwide Inpatient Sample. Intensive Care Med. 2012;38:1143-1151.

Worse Stroke Outcomes on Weekends

Clinical question: Does the day of admission alter the quality and safety of care received by stroke patients?

Background: There is growing concern of disparities in care between weekday and weekend admissions in many health conditions. Recent studies have sought to determine if such a disparity exists for stroke patients.

Study design: Retrospective cohort study.

Setting: National Health Service public hospitals, England.

Synopsis: This study evaluated six quality-safety indicators among 93,621 stroke admits from April 1, 2009, to March 31, 2010. Investigators found performance on five of six indicators was significantly worse on weekends. Specifically, the percent of same-day brain scans was 43.1% on weekends, compared with 47.6% on weekdays, and seven-day in-hospital mortality for Sunday admissions was 11%, compared with an overall mean mortality of 8.9%.

It is possible that some of the observed effect could be due to unmeasured differences in patients admitted on weekends compared to weekdays.

Bottom line: This study suggests that, similar to other clinical conditions, significant disparities might exist between weekend and weekday care of stroke patients.

Citation: Palmer WL, Bottle A, Davie C, Vincent CA, Aylin P. Dying for the weekend: a retrospective cohort study on the association between day of hospital presentation and the quality and safety of stroke care. Arch Neurol. 2012;9:1-7.

Hospital Admissions from Emergency Departments Increasing

Clinical question: What proportion of current hospital admissions use the ED as an admission portal?

Background: Historically, outpatient providers’ offices admitted clinically stable patients with acute problems. From 1997 to 2007, ED visit rates increased by more than a third. Currently, a quarter of all acute-care outpatient visits occur in the ED.

Study design: Retrospective, observational cohort study.

Setting: The Nationwide Inpatient Sample (NIS) database, with approximately 8 million annual hospital stays, weighted to produce national averages.

Synopsis: NIS data from 1993 to 2006 showed the number of hospital admissions increased by 15%, while the proportion of admissions from the ED increased by 50%. The total proportion of inpatients entering from the ED increased to 43.8% from 33.5% (P<0.001). Twelve of the 13 most frequent inpatient clinical conditions also had a proportional increase in admissions from the ED (P<0.0001).

Possible explanations for the increases include difficulty arranging timely outpatient sick visits and overuse of the ED for issues that could be more appropriately addressed by primary-care offices. Furthermore, public education campaigns for heart attack or stroke emphasize early emergency care. Patients and providers expect rapid specialized care and early treatment that is readily available in ED.

More efficient use of inpatient resources is a focus of the Affordable Care Act. To inform health policy, research is needed to determine the drivers of admission trends, as well as the value and cost of emergency care.

Bottom line: The proportion of hospital admissions from the ED is increasing, but the implications for healthcare delivery are inadequately understood.

Citation: Schuur JD, Venkatesh AK. The growing role of emergency departments in hospital admissions. N Engl J Med. 2012;367(5):391-393.

Avoiding Intensive Glucose Control in Acute Stroke

Clinical question: Is intensive insulin treatment beneficial in patients with acute stroke?

Background: Although post-stroke hyperglycemia is associated with worse outcomes in acute stroke patients, it is unknown if intensive insulin treatment improves prognosis or infarct size.

Study design: Unblinded randomized controlled trial.

Setting: Single academic medical center in France.

Synopsis: Study authors randomized acute stroke patients (NIHSS from 5 to 25) to intensive insulin treatment or subcutaneous insulin therapy within 24 hours of admission. Initial median blood sugars were ~120 mg/dL in both groups. Mean blood sugars of <126 mg/dL were achieved at 24 hours in 95% of the intensive group and 67% of the subcutaneous group. The MRI infarct size at follow-up scanning was significantly larger in the intensive insulin group, but there were no differences in functional outcomes, serious adverse events, or mortality between the groups.

The study might have been underpowered to detect meaningful clinical differences between the groups.

Bottom line: Intensive blood sugar control cannot be recommended in acute stroke patients.

Citation: Rosso C, Corvol JC, Pires C, et al. Intensive versus subcutaneous insulin in patients with hyperacute stroke: results from the randomized INSULINFARCT trial. Stroke. 2012;43(9):2343-2349.

Peri-Procedural Bleeding with Dabigatran Versus Warfarin

Clinical question: Is dabigatran more likely to result in periprocedural bleeding when compared to warfarin?

Background: In a randomized clinical trial (RE-LY), dabigatran had a lower risk of major bleeding compared with warfarin. However, given that the anticoagulant effect of dabigatran is difficult to measure and there is not an effective antidote, it is unknown if dabigatran is associated with higher periprocedural rates of bleeding compared with warfarin.

Study design: Post-hoc analysis of the RE-LY trial.

Setting: Multicenter randomized controlled trial.

Synopsis: Patients enrolled in the RE-LY trial all had urgent or elective-invasive procedures recorded. The protocol recommended cessation of warfarin based on local practice, and cessation of dabigatran 24 hours before the procedure; the protocol was amended in 2008 to recommend cessation of dabigatran 24 hours before low-bleeding risk procedures, but two to five hours before high-bleeding-risk procedures (depending on renal function). Periprocedural bleeding was defined as seven days prior and 30 days after the procedure. Dabigatran was interrupted a mean of 49 hours before the procedures, and warfarin for 114 hours. There was no significant difference in major bleeding rates between dabigatran (150-mg dose) and warfarin, which occurred in 5.1% versus 4.6% patients, respectively.

Bottom line: Warfarin and dabigatran have about the same rate of periprocedural bleeding rates, but interruption duration is shorter for dabigatran.

Citation: Healey JS, Eikelboom J, Douketis J, et al. Peri-procedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the randomized evaluation of long-term anticoagulation therapy (RE-LY) randomized trial. Circulation. 2012;126(3):343-348.

Clinical Shorts


The FDA approved a test that detects the dengue virus from a blood sample (as opposed to older antibody tests). It is easy to perform and likely will be readily available in the near future.

Citation: Centers for Disease Control and Prevention. Centers for Disease Control and Prevention briefing. Centers for Disease Control and Prevention website. Available at: Accessed Sept. 3, 2012.


This prospective cohort of critically ill patients on antibiotics and CVVHD found wide variability of trough levels of various antibiotics, necessitating routine checking of levels to avoid under- and overdosing.

Citation: Roberts DM, Roberts JA, Roberts MA, et al. Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: a multicenter pharmacokinetic study. Crit Care Med. 2012;40(5):1523-1528.


This large prospective analysis of patients with gross hematuria found no pathology in ~50% but found cancer in ~20%, necessitating a full workup in these types of patients.

Citation: Mishriki SF, Vint R, Somani BK. Half of visible and half of recurrent visible hematuria cases have underlying pathology: prospective large cohort study with long-term follow-up. J Urol. 2012;187(5):1561-1565.

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