Recent Research

Criteria for cardiac catheterization, subclinical hyperthyroidism and CHD risk, and more.

Two common arousal/sedation tools are interchangeable for CAM-ICU eligibility

Two commonly used arousal/sedation tools perform similarly in assessing ICU patients' eligibility for delirium screening, a study found.

Researchers sought to determine the concordance of the Richmond Agitation Sedation Scale (RASS) and the Riker Sedation-Agitation Scale (SAS) for determining eligibility of screening with the Confusion Assessment Method for the ICU (CAM-ICU). They performed a prospective cohort study in the adult medical, surgical and step-down ICUs of an academic hospital in Indianapolis with a cohort of 975 consecutive ICU admissions. Two pharmacists performed the assessments 48 hours after ICU admission and then daily afterward until a patient became delirious died, or was discharged. The SAS was applied first, then the RASS, by the same assessor. A RASS cutoff of >−4 and a SAS cutoff of >2 were used to identify patients eligible for the CAM-ICU. Results were published in the July Chest.

The prevalence of delirium in all ICU patients was 13%; it was 50.6% in mechanically ventilated patients. Thirty percent of RASS scores were −5 and −4 (coma), 7% were −3 to −1 (sedated), 62.6% were 0 (calm) and 0.4% were +1 to +3 (restless, agitated). For the SAS, 66.5% indicated a calm state (score of 4), 32.8% a sedated state (score of 1 to 3) and 0.6% an anxious or agitated state (score of 5 to 6). The Spearman rank correlation between the scores was estimated as 0.91. Seventy percent of screens were eligible for CAM-ICU assessment using a RASS score of −3 or higher versus 72% using a SAS score of 3 or higher. The agreement between the tools via kappa coefficient was 0.93.

The RASS and SAS can be used interchangeably to assess level of consciousness and eligibility for the CAM-ICU, the authors concluded. Study strengths include its relatively large sample size and diverse patient population, with a high proportion of minority patients and inclusion of medical and surgical patients. The study's main limitation was its inclusion of step-down patients, most of whom weren't mechanically ventilated. This resulted in a large number of RASS scores of 0 and SAS scores of 4 “which could have resulted in an artificially inflated correlation coefficient,” the authors wrote.

Criteria describe appropriate use of cardiac catheterization

New criteria provide guidance on when cardiac catheterization is appropriate to evaluate patients for heart disease. The appropriate use criteria were released by the American College of Cardiology Foundation and the Society for Cardiovascular Angiography and Interventions.

The expert panel that developed the criteria identified 166 possible clinical scenarios in which diagnostic catheterization might be considered and then divided them into appropriate, inappropriate and uncertain uses. Cardiac catheterization was determined to be appropriate in 75 of the situations, uncertain in 49 and inappropriate in 42. The authors noted that use of catheterization is still reasonable in the uncertain situations, so that designation should not be used as grounds for denial of reimbursement.

The criteria primarily focus on the use of catheterization to detect blockages in the arteries that are indicative of coronary artery disease (CAD), but the panel also considered a number of other areas, including arrhythmia workup, preoperative testing and possible valve disease or pulmonary hypertension.

Among other situations, the panel advised that cardiac catheterization is appropriate in patients:

  • without prior stress testing but who report symptoms and have a high pretest probability of heart disease, or high likelihood of disease in the physician's judgment;
  • with definite or suspected acute coronary syndrome;
  • with typical symptoms and intermediate- or high-risk findings on prior diagnostic testing.

The panel noted certain situations in which individuals should not be referred directly to cardiac catheterization. Among others, these include:

  • asymptomatic patients at low risk for CAD or without significant symptoms suggestive of heart disease;
  • patients preparing for non-cardiac surgery who have good functional or exercise capacity and/or
  • patients undergoing low-risk surgeries (If a patient has significant risk factors or is undergoing transplantation or heart valve surgery, diagnostic catheterization is warranted, the experts said).

These criteria will be translated into order sheets and decision support tools by the writing organizations. They were developed in collaboration with the American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography and Society for Cardiovascular Magnetic Resonance and the Society of Thoracic Surgeons. The criteria were published in the May 29 Journal of the American College of Cardiology as well as in Catheterization and Cardiovascular Interventions and the Journal of Thoracic and Cardiovascular Surgery.

Subclinical hyperthyroidism associated with CHD risk, mortality, study indicates

Subclinical hyperthyroidism is associated with increased risk for total mortality, coronary heart disease (CHD) mortality, and incident atrial fibrillation, according to a recent study.

Researchers examined pooled individual data from 52,674 participants in 10 large, prospective cohorts to determine the association between endogenous subclinical hyperthyroidism and risks of total and CHD death, CHD events, and atrial fibrillation. Six cohorts had data available on CHD events in 22,437 participants, and five cohorts had data available on incident atrial fibrillation in 8,711 participants. The median age of participants was 59 years, and 58.5% were women. The authors defined euthyroidism as a thyrotropin level of 0.45 mIU/L to 4.49 mIU/L and endogenous subclinical hyperthyroidism as a thyrotropin level below 0.45 mIU/L with normal free thyroxine levels when participants taking thyroid-altering medications were excluded. The study results were published in the May 28 Archives of Internal Medicine.

A total of 2,188 (4.2%) of the 52,674 participants had endogenous subclinical hyperthyroidism. Overall, 8,527 participants died during follow-up, 1,896 from CHD. CHD events occurred in 3,653 of 22,437 participants and atrial fibrillation developed in 785 of 8,711 participants. Subclinical hyperthyroidism was found to be associated with increased total mortality, CHD mortality, CHD events and atrial fibrillation in analyses adjusted for age and sex. No differences in risk were seen by age, sex or preexisting cardiovascular disease, and risk remained similar after adjustment for cardiovascular risk factors. Participants with a thyrotropin level below 0.10 mIU/L had a higher risk for CHD death and atrial fibrillation than those with a thyrotropin level between 0.10 and 0.44 mIU/L.

The authors acknowledged that their study involved mainly white participants, that thyroid function was tested only at baseline, and that other conditions that could have affected mortality were not assessed, among other limitations. However, they concluded that an association exists between endogenous subclinical hyperthyroidism and risk for total mortality, CHD mortality and incident AF. Risks for CHD mortality and atrial fibrillation are highest with a thyrotropin level below 0.10 mIU/L, they noted.

An accompanying editorial also noted the study's limitations but said it provides important information about the importance of subclinical hyperthyroidism in clinical practice. “Until further data are available, the relationship between subclinical hyperthyroidism and increased mortality, CHD mortality and atrial fibrillation presently provides sufficient evidence to consider treatment of subclinical hyperthyroidism, especially in elderly patients with cardiac risks, hyperthyroid symptoms, or osteoporosis,” the editorialist wrote.

Fluoroquinolones associated with retinal detachment

Current users of oral fluoroquinolones are nearly five times more likely to have a retinal detachment than nonusers, although the absolute risk was small, a study found.

To examine the association between use of oral fluoroquinolones and the risk of developing a retinal detachment, researchers conducted a nested case-control study of patients in British Columbia, Canada, who had visited an ophthalmologist between January 2000 and December 2007.

Current users were those with a prescription that overlapped the index date. A recent user was defined as having a prescription 1 to 7 days prior to the index date, and a past user was defined as having a prescription 8 to 365 days before the index date.

As an additional control, researchers also examined the risk of retinal detachment against two drug classes not associated with retinal detachment: oral β-lactam antibiotics (all oral penicillins and cephalosporins) and short-acting β-agonists.

Results appeared in the April 4 Journal of the American Medical Association.

Among 989,591 patients, 4,384 cases of retinal detachment and 43,840 controls were identified. Current use of fluoroquinolones was associated with a higher risk of developing a retinal detachment (3.3% of cases vs. 0.6% of controls; adjusted rate ratio [ARR], 4.50). Neither recent use (0.3% of cases vs. 0.2% of controls; ARR, 0.92) nor past use (6.6% of cases vs. 6.1% of controls; ARR, 1.03) was associated with a retinal detachment. There was no evidence of an association between retinal detachments and β-lactam antibiotics (ARR, 0.74) or short-acting β-agonists (ARR, 0.95).

The absolute increase in the risk of a retinal detachment associated with fluoroquinolones was 4 per 10,000 person-years. The number needed to harm was 2,500 for any use of fluoroquinolones.

The retina is attached to the cortical vitreous by collagen fibers, and fluoroquinolones have been shown to interfere with collagen synthesis. Just two doses of oral ciprofloxacin can reach antibacterial concentration in the vitreous, the authors noted. Although the absolute risk is small, fluoroquinolones are a commonly prescribed drug and 40% of people who experience a detachment could permanently lose at least some visual acuity, they noted.

No compelling reason for warfarin over aspirin for LVEF, study indicates

There was no significant overall difference in the primary outcome between warfarin and aspirin among patients with reduced left ventricular ejection fraction (LVEF) who were in sinus rhythm, researchers reported.

A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage, among other tradeoffs noted in the study.

Researchers designed a cooperative, double-blind, multicenter clinical trial at 168 centers in 11 countries looking at warfarin use with a target international normalized ratio of 2.0 to 3.5 or 325 mg of aspirin per day. The trial was sponsored by the National Institutes of Health (NIH). Researchers followed 2,305 patients for up to six years and looked for the primary outcome of time to ischemic stroke, intracerebral hemorrhage or death from any cause. Results appeared in the May 17 New England Journal of Medicine.

Overall, 622 patients (27%) had one of the three primary outcomes (531 deaths [85.4%], 84 ischemic strokes [13.5%], and 7 intracerebral hemorrhages [1.1%]). There were 7.47 events per 100 patient-years in the warfarin group and 7.93 events per 100 patient-years in the aspirin group (hazard ratio with warfarin, 0.93; 95% CI, 0.79 to 1.10; P=0.40).

There was a constant and significant benefit with warfarin compared to aspirin for the rate of ischemic stroke (HR, 0.52; 95% CI, 0.33 to 0.82; P=0.005). There was no significant difference between the groups for the first event in the composite of death, ischemic stroke, intracerebral hemorrhage, myocardial infarction, or hospitalization for heart failure (HR with warfarin, 1.07; 95% CI, 0.93 to 1.23; P=0.33). Rates of myocardial infarction and hospitalization for heart failure did not differ significantly between the two groups.

The rate of major hemorrhage was significantly higher with warfarin than with aspirin (1.78 events per 100 patient-years with warfarin vs. 0.87 event per 100 patient-years with aspirin; adjusted rate ratio, 2.05; 95% CI, 1.36 to 3.12; P<0.001). However, the rates of intracerebral and intracranial hemorrhages combined did not differ significantly according to treatment group (0.27 event per 100 patient-years in the warfarin group and 0.22 event per 100 patient-years in the aspirin group; P=0.82). Major gastrointestinal bleeding occurred more frequently in the warfarin group (0.94 event per 100 patient-years vs. 0.45 event per 100 patient-years in the aspirin group; P=0.01).

The authors wrote, “Given the finding that warfarin did not provide an overall benefit and was associated with an increased risk of bleeding, there is no compelling reason to use warfarin rather than aspirin in patients with a reduced LVEF who are in sinus rhythm.”

Editorialists commented that “The careful conduct of this blinded trial, in which patients in the warfarin group had good control of INR levels (mean time in the therapeutic range after a 6-week period of dose adjustment, 62.6%) and which included more than 600 primary outcome events, has provided clinicians with clear answers. ... The lack of an effect of warfarin on mortality suggests that most of the deaths in these patients with heart failure, who had severe impairment of left ventricular function, are unrelated to thromboembolism and, instead, are most likely due to pump failure or ventricular arrhythmias.”

Thrombolytic therapy effective, underused in unstable patients with acute PE

Thrombolytic therapy improves mortality in unstable patients with acute pulmonary embolism (PE) but is underused, according to a recent study.

Researchers used 1999-2008 data from the U.S. National Inpatient Sample to determine the in-hospital all-cause mortality rate by treatment in unstable patients with acute PE who were discharged from short-stay hospitals. “Unstable” was defined as being in shock or ventilator-dependent. The study results appeared in the May American Journal of Medicine.

The study included data on 72,230 unstable patients with acute PE, 21,390 of whom (30%) received thrombolytic therapy. Patients who received thrombolytic therapy had an in-hospital all-cause case fatality rate of 15% (3,105 of 21,390) versus 47% (23,820 of 50,840) among patients who did not (P<0.0001), while patients who received thrombolytic therapy plus a vena cava filter had an all-cause case fatality rate of 7.6% (505 of 6,630) versus 33% (4,260 of 12,850) in patients who received a filter alone. PE-specific case fatality rate was 8.4% (820 of 9,810) in patients with thrombolytic therapy versus 42% (1,080 of 2,600) in those without, and 2.7% (70 of 2,590) in patients who received thrombolytic therapy plus a vena cava filter versus 27% (160 of 600) in patients who received a filter alone (P<0.0001). The percentage of unstable patients receiving thrombolytic therapy decreased linearly from 40% in 1999 to 23% in 2008.

The authors noted that patients who received thrombolytic therapy were younger and had fewer comorbid conditions, but they did not feel these factors were enough to explain the large differences in case fatality rates. They concluded that both in-hospital all-cause case fatality rate and case fatality rate due to PE alone were significantly better in patients who received thrombolytic therapy. Thrombolytic therapy led to better case fatality rates than vena cava filters alone, and both therapies combined decreased case fatality rates even further.

The author of an accompanying editorial called the findings “dramatic” and said that “thrombolytic therapy (in those without contraindications) plus vena cava filters are the appropriate therapy for hemodynamically unstable patients with pulmonary embolism who face an approximately 50% mortality with standard anticoagulant therapy without vena cava filters.”

Score predicts hemorrhage risk in ischemic stroke patients treated with thrombolysis

Researchers developed a score to predict risk of symptomatic intracerebral hemorrhage in acute ischemic stroke patients who receive intravenous thrombolysis, a recent study reported.

Researchers analyzed data from 31,627 patients from the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register who presented with stroke symptoms and were given intravenous alteplase. The outcome, symptomatic intracerebral hemorrhage (SICH), was defined as a Type 2 parenchymal hemorrhage, with deterioration in National Institutes of Health Stroke Scale (NIHSS) score of ≥4 points or death. Risk factors associated with the outcome were entered into a logistic regression model. Adjusted odds ratios for independent risk factors were converted into points that were added together to create a risk score between 0 and 12.

Overall rate of SICH was 1.8%. Researchers found 10 independent risk factors for SICH. By order of importance, they were: use of combined aspirin and clopidogrel; use of aspirin monotherapy; baseline NIHSS score ≥13 or between 7 and 12; serum glucose level ≥180 mg/dL; age ≥72 years; systolic blood pressure ≥146 mm Hg; weight ≥95 kilograms; onset-to-treatment time ≥180 minutes; and history of hypertension. The risk score showed a >70-fold graded increase in the rate of SICH for patients with a score of ≥10 points (14.3% of patients) compared with a score of 0 (0.2% of patients). Eleven percent of patients scored ≥7 points, showing a rate of SICH of ≥3.7%, or at least double the population average. Results appeared in the May Stroke.

A method of identifying patients at low risk of SICH may encourage use of thrombolysis by reluctant nonspecialists, the authors wrote. In general, the risk score can aid clinicians, patients and family members in making decisions about using thrombolysis in acute stroke, they added. It could also be used in conjunction with biomarkers and neuroimaging, as these evolve in their ability to predict SICH, they said. External validation of the score is needed, as is a study of the clinical effect of thrombolysis across risk score categories, to assess whether patients at high risk of SICH may still be better off with treatment, they noted.

UFH, LMWH similar in cost, efficacy for VTE prophylaxis

Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) have similar costs and effectiveness for venous thromboembolism (VTE) prophylaxis, but LMWH is associated with fewer complications, a recent study found.

In a retrospective cohort study using a national sample of hospitals, researchers compared the risk of VTE, bleeding, heparin-induced thrombocytopenia (HIT), and death associated with UFH and LMWH. Patients in the study had been discharged between Jan. 1, 2004 and June 30, 2005 from 333 acute care facilities that participated in Premier's Perspective database. All 32,104 patients had an ICD-9-CM diagnosis code that put them at moderate-to-high risk of VTE (congestive heart failure, stroke, pneumonia, or urinary tract infection), and received daily prophylactic dosages of either 40 mg LMWH or 10,000-15,000 units of UFH by hospital day 2. Patients received medication until discharge or until they developed a VTE or a complication related to heparin. Hospital-acquired VTE was defined as a secondary diagnosis of VTE combined with a diagnostic test for VTE after hospital day two, followed by treatment for VTE for at least half of remaining hospital days, or until warfarin was started or a complication occurred (like transfusion). Patients readmitted within 30 days with a primary diagnosis of VTE were also considered to have hospital-acquired VTE.

Fifty-five percent of patients received LMWH and 45% received UFH. VTE occurred in 163 (0.51%) patients, and complications that led to stopping therapy were rare (<0.2%). In propensity-adjusted analysis, patients treated with UFH had a non-significant odds ratio for VTE of 1.04 compared to LMWH. In a grouped treatment model, the odds of VTE with UFH was non-significant at 1.14. Adjusted odds of bleeding with UFH compared to LMWH were 1.64 (95% confidence interval [CI], 0.50-5.33); adjusted odds of complications that halted prophylaxis were 2.84 (95% CI, 1.43-45.66); and adjusted cost ratio was 0.97 (95% CI, 0.90-1.05). Hospitals that mostly used UFH had a transfusion rate of 0.60% versus 0.76% at hospitals that mostly used LMWH (P=0.54), indicating that the higher risk of major bleeding associated with UFH was not confounded by local transfusion practices. Results were published online April 2 by the Journal of Hospital Medicine.

Previous randomized controlled trials comparing LMWH and UFH have been small, industry-funded and “used endpoints of uncertain significance” (like asymptomatic DVT assessed by ultrasound), the authors noted. While the current study found no difference in effectiveness or cost of the two treatments, LMWH was less likely to be associated with bleeding. “In addition, LMWH is more convenient since it can be dosed once daily, and for that reason may be more acceptable to patients,” the authors wrote. “For these reasons, LMWH may be the drug of choice for inpatient prophylaxis of general medical patients.”

Low-dose CT scan noninferior for appendicitis diagnosis

For young adults with suspected appendicitis, scanning with low-dose computed tomography (CT) resulted in the same rate of unnecessary appendectomies as the standard dose, according to a recent study.

In the single-center noninferiority trial conducted in Korea, 891 patients with suspected appendicitis were randomized to either low-dose CT or standard-dose CT. The median radiation dose was 116 mGY · cm in the low-dose group and 521 mGY · cm in the standard group. Results were published in the April 26 New England Journal of Medicine.

The low- and high-dose groups did not differ significantly in their rates of negative appendectomy (3.5% with low-dose vs. 3.2% with high-dose) or appendiceal perforation (26.5% vs. 23.3%, P=0.46). Patients in the low-dose group had a nonsignificantly greater need for additional imaging (3.2% vs. 1.6%, P=0.09) and had a longer median interval between CT and appendectomy (7.1 hours vs. 5.6 hours), which researchers suggested could be due to physicians' hesitation to base their decisions on low-dose CT results.

However, based on the results of the study, the authors concluded that low-dose CT is noninferior to high-dose with regard to negative appendectomies and may be used for first-line imaging of suspected appendicitis. They did note, however, that in the center where the study was conducted, few of the patients were obese and the radiologists were expert in interpretation of low-dose CT, so generalizability may be limited.

And while the purpose of the study (which was sponsored by a CT scanner manufacturer) was to find a less potentially carcinogenic method of diagnosing appendicitis for young adults, the authors added a caveat on that question as well, writing “it is highly debatable whether the radiation levels used in our two groups can actually induce cancer.”