Recent Research

Transfusion strategies, hyponatremia at admission, follow-up timing and medication adherence, and more.


Liberal transfusion strategies may be preferred in patients with cardiovascular disease

Liberal blood transfusion strategies may be preferred to restrictive strategies in anemic patients with cardiovascular disease (CVD), a recent study suggests.

Researchers performed a systematic review and meta-analysis of trials published through Nov. 2, 2015, to compare outcomes of restrictive and liberal blood transfusion strategies in patients who had CVD but were not having cardiac surgery. The main outcome measures were 30-day mortality and cardiovascular events. Results were published online March 29 by The BMJ.

Eleven trials involving 3,033 patients with CVD were included in the meta-analysis. Three trials involved orthopedics, 1 involved upper gastrointestinal bleeding, 2 involved acute coronary syndrome or myocardial infarction, 4 involved critical care, and 1 involved elective aortic and infrainguinal revascularization. Restrictive transfusion was used in 1,514 patients, and liberal transfusion was used in 1,519 patients. Restrictive strategies used hemoglobin levels ranging from 7.0 to 9.7 g/dL, while liberal strategies used hemoglobin levels ranging from 9.0 to 11.3 g/dL.

One hundred forty-four patients (9.5%) managed with a restrictive transfusion strategy died at 30 days versus 126 (8%) managed with a liberal transfusion strategy (pooled risk ratio, 1.15; 95% CI, 0.88 to 1.50; P=0.50). Acute coronary syndrome incidence ranged from 0% to 20.4% in the restrictive arms and 0% to 11.1% in the liberal arms (risk ratio, 1.78; 95% CI, 1.18 to 2.70; P=0.01).

In addition to other limitations of the study, the authors noted that the patient populations in the included trials exhibited significant clinical diversity and that the thresholds for restrictive and liberal transfusion strategies also varied, with overlapping cutoff values. However, they concluded that based on their review, restrictive transfusion thresholds, which are usually defined as a hemoglobin level of 7.0 to 8.0 g/dL, are associated with higher acute coronary syndrome rates than liberal thresholds, typically defined as a hemoglobin level of 9.0 to 10.0 g/dL. The authors noted that mortality and other important outcomes did not appear to be affected and that the quality of evidence was low. Still, they suggested that a more liberal transfusion threshold be used in patients with acute and chronic CVD until more high-quality data are available.

Study finds no difference between N95 masks, surgical masks in clinical settings

A meta-analysis found insufficient evidence to determine if there is a difference between N95 respirators and surgical masks for associated risk of laboratory-confirmed respiratory infection, influenza-like illness, or reported workplace absenteeism in health care workers.

Researchers performed a systematic review of studies published from January 1990 to December 2014 for clinical and surrogate exposure data comparing N95 respirators and surgical masks for prevention of transmissible acute respiratory infections. There were 6 clinical studies (3 randomized controlled trials [RCTs], 1 cohort study, and 2 case-control studies) that included data on health care workers wearing N95 respirators and surgical masks to prevent acute respiratory infections. There were also 23 surrogate exposure studies comparing N95 respirators and surgical masks using mannequins or adult volunteers under simulated conditions.

Outcomes from clinical studies were laboratory-confirmed respiratory infection, influenza-like illness, and workplace absenteeism. Outcomes from surrogate exposure studies were filter penetration, face-seal leakage, and total inward leakage. Results were published by CMAJ on March 7.

There was no significant difference between N95 respirators and surgical masks in associated risk of:

  • laboratory-confirmed respiratory infection (RCTs: odds ratio [OR], 0.89 [95% CI, 0.64 to 1.24]; cohort study: OR, 0.43 [95% CI, 0.03 to 6.41]; case-control studies: OR, 0.91 [95% CI, 0.25 to 3.36]);
  • influenza-like illness (RCTs: OR, 0.51 [95% CI, 0.19 to 1.41]); or
  • reported workplace absenteeism (RCT: OR, 0.92 [95% CI, 0.57 to 1.50]).

In the surrogate exposure studies, N95 respirators were associated with less filter penetration, less face-seal leakage, and less total inward leakage under laboratory experimental conditions compared with surgical masks. “However, transmission of acute respiratory infections is a complex process that may not be appropriately replicated by surrogate exposure studies,” the authors wrote. “Because the face seal is important for the efficiency of the N95 respirator, fit-testing is recommended for health care workers. N95 respirators are often considered uncomfortable for regular use, and improper wearing or adjustment of the respirator because of discomfort could lead to inadvertent face contamination, thus negating the potential protective benefit.”

The authors concluded that N95 respirators appeared to have a protective advantage over surgical masks in laboratory settings but that there were insufficient data to determine definitively whether they are superior in clinical settings. They called for additional large RCTs to be performed in this area.

Hyponatremia at admission predicts mortality, study finds

Hyponatremia that is present on admission or worsens during hospitalization predicts mortality in hospitalized heart failure patients, a recent study found.

The observational study included 2,556 Taiwanese patients hospitalized for acute heart failure. Their average age was 76.4 years, and 67% were men. The primary outcomes of the study were all-cause and cardiovascular mortality, with a follow-up of up to 4 years. Results were published by the Journal of the American Heart Association on March 23.

Hyponatremia was defined as a serum sodium level <135 mEq/L, and 360 studied patients met this criteria on the first day of hospitalization. Compared to those without hyponatremia, they had a significantly higher risk of all-cause mortality (hazard ratio [HR], 1.43; 95% CI, 1.11 to 1.83) and cardiovascular mortality (HR, 1.50; 95% CI, 1.04 to 2.17), independent of age, sex, hematocrit, estimated glomerular filtration rate, left ventricular ejection fraction, and prescribed medications.

The investigators found a dose-response relationship, with patients having severe hyponatremia (serum sodium level <125 mEq/L) having even higher mortality risk. Worsening of sodium levels during hospitalization (defined as a drop >3 mEq/L) was also associated with increased mortality risk, both in patients with hyponatremia on admission and those without. The associations between hyponatremia and mortality held true in the study's subgroup analyses.

Hyponatremia on admission has been previously associated with mortality in heart failure patients, the authors noted. The key question now is whether hyponatremia contributes to or just predicts outcomes. This study's finding that more severe hyponatremia was associated with worse outcomes “may support that patients with severe hyponatremia would be more likely to get benefits by correcting serum sodium levels,” the authors said. They concluded that both admission hyponatremia and changes in sodium levels during hospitalization could potentially be used in risk assessment of hospitalized heart failure patients.

Follow-up within 6 weeks of discharge for acute MI linked to greater medication adherence

Timely outpatient follow-up in older patients discharged after acute myocardial infarction (MI) is associated with greater long-term adherence to secondary risk prevention medications, a recent study found.

Researchers used the Acute Coronary Treatment and Intervention Outcomes Network Registry and longitudinal Medicare Part D prescription fill data to examine medication adherence among 20,976 acute MI patients (49.5% men; mean age, 75.8 years) discharged between Jan. 2, 2007, and Oct. 1, 2010, from 461 U.S. hospitals. Results of the retrospective analysis were published online March 23 by JAMA Cardiology.

Overall, 5,542 (26.4%) patients attended a follow-up visit within 1 week of discharge; 5,246 (25.0%) followed up between 1 and 2 weeks of discharge; 6,830 (32.6%) followed up between 2 and 6 weeks of discharge; and 3,358 (16.0%) had not followed up within 6 weeks of discharge.

Overall adherence rates at 90 days and 1 year postdischarge were 68.7% and 61.1% for beta-blockers, 63.8% and 54.4% for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, 63.4% and 55.8% for statins, and 64.2% and 63.5% for platelet P2Y12 receptor inhibitors, respectively.

Compared to patients who had follow-up visits within 1 week, medication adherence rates among those who followed up within 1 to 2 weeks and 2 to 6 weeks were not significantly different. However, patients who took longer than 6 weeks to follow up had lower composite medication adherence (P<0.001; adjusted odds ratio, 0.74 [95% CI, 0.70 to 0.77]).

Compared with patients with earlier follow-up, those with longer times between discharge and their first appointment were more likely to be men, to be black, and to live in communities with lower median household income, lower median home value, and lower rates of high school and college educational levels. They were also more likely to have been transferred from another hospital, less likely to have undergone percutaneous coronary intervention, and more likely to have undergone coronary artery bypass graft surgery. Overall morbidity and in-hospital complications did not differ significantly between groups.

The authors noted limitations to their study, such as its retrospective design and the likelihood of residual confounders. In addition, its data source was based on prescriptions filled, not taken, and did not allow for distinguishing appropriate medication discontinuation from plain nonadherence.

Adding midodrine to vasopressor reduced duration of therapy, ICU stay

For recovering septic shock patients, treatment with midodrine may reduce duration of vasopressors, a recent study found.

The retrospective observational study included 275 patients in a single medical ICU. All of the patients had a diagnosis of septic shock and had required at least 24 hours of IV vasopressors before demonstrating clinical stability with stable or decreasing vasopressor doses. One hundred forty of them received only an IV vasopressor, while 135 took oral midodrine along with the vasopressor. Results were published in the March CHEST.

The midodrine group had a significantly shorter duration of IV vasopressor therapy (2.9 days vs. 3.8 days; P<0.001), as well as a lower rate of reinstitution of vasopressors after discontinuation (5.2% vs. 15%; P=0.007). ICU length of stay was 7.5 days in the midodrine group compared to 9.4 days in the vasopressor-only group (P=0.017). The only complication of midodrine was 1 patient who developed transient bradycardia, which resolved upon discontinuation of midodrine.

The results indicate that midodrine “is a safe and effective method” to reduce the duration of IV vasopressors and ICU length of stay in patients recovering from septic shock, the authors said. They noted that because their hospital policy does not permit IV vasopressor use outside the ICU, midodrine therapy allowed patients to be transferred off the critical care unit sooner. Although the studied groups were similar in age, gender, and severity of illness scores, unmeasured variables could have confounded the results, they cautioned.

“This preliminary study demonstrates the safety of this practice and lays the groundwork for a prospective randomized controlled trial which will examine efficacy, starting dose, escalation, tapering, and appropriate patient selection for midodrine use during recovery from septic shock,” the authors concluded.