Journal watch: recent studies of note

Recent studies about pre-surgery beta-blockers, sepsis perception##mdash;practice gaps, and other topics.

Pre-surgery beta-blockers reduce mortality in COPD patients

Contrary to common practice, giving beta blockers before surgery may significantly reduce mortality in people with chronic obstructive pulmonary disease (COPD), according to a prospective study. A dosage of more than 25% of the maximum recommended amount was found to be most effective in both the short and long term.

Researchers evaluated outcomes for more than 3,000 consecutive patients who underwent vascular surgery from 1990 to 2006 to determine the relationship between beta blockers and COPD. Of the entire cohort, there were 1,205 with COPD, 462 of whom received beta blockers. In the month after surgery, COPD patients who did not receive beta-blockers were twice as likely to die as those who did (8% vs. 4%). Within the long-term follow-up period, 40% of COPD patients on beta-blockers died, whereas 67% who were not on beta-blockers died.

The study, published in the Oct. 1 issue of the American Journal of Respiratory and Critical Care Medicine, focused on the effect of low dose beta-blockers (less than 25% of the maximum recommended therapeutic dose) vs. an intensified dosage of more than 25% of the maximum recommended therapeutic dose. The intensified dose was associated with both reduced 30- day and long-term mortality in patients with COPD, whereas the low dose was not.

Of the patients evaluated, 31% received cardio-selective beta-blockers, and there were no identifiable clinical differences between the patients with COPD and those without. The researchers also found that the cardio-selective beta-blockers were independently associated with reduced 30-day mortality in both patients with and without COPD.

Sepsis study reveals gap between perception and practice

There is a significant gap between actual practice and perceptions with respect to sepsis treatment in intensive care units (ICU), according to a one-day, country-wide sample study facilitated by the German Sepsis Competence Network (SepNet).

More than 200 randomly selected hospital ICUs in Germany were evaluated for adherence to several recommendations, including low-tidal volume (Vt) ventilation in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and glycemic control. According to the literature, tight glycemic control in ICU patients as a preventive approach results in both decreased frequency of sepsis and reduced overall mortality, and lung protective ventilation reduces absolute mortality in patients with ARDS by 9%.

The cohort comprised 366 patients. Of those, 152 had ALI or ARDS. The mean tidal volume was 10.0 ± 2.4 mL/kg of their predicted body weight. Euglycemia (4.4 to 6.1 mmol/L) was noted in 6.2% of patients; 33.8% of the entire cohort had blood glucose levels less than 8.3 mmol/L and 66.2% were hyperglycemic with blood glucose levels greater than 8.3 mmol/L.

Overall, mean maximal glucose level was 10.0 ± 3.6 mmol/L. The study was published in the October issue of Critical Care Medicine.

While most patients did not receive recommended therapies, a majority of ICU directors reported that they adhered to the recommendations: 79.9% of ICU directors said they adhered to low-Vt ventilation, whereas only 2.6% of patients received Vt ≤6 mL/kg PBW and 65.9% of ICU directors reported adhering to glycemic control, whereas only 6.2% of patients were euglycemic.

Interestingly, perceived adherence was higher in academic and larger hospitals, while actual practice was not significantly different based on hospital size or university affiliation.

Studies support safety and efficacy of extended tPA treatment window

Thrombolysis with alteplase may be safe and effective up to four-and-a-half hours after onset of acute ischemic stroke despite the currently approved three-hour treatment window, according to two new studies.

The potential for increased risk of hemorrhage has been the rationale for limiting use of tissue plasminogen activator (tPA) to within three hours of stroke onset. However, when researchers in an international, observational study compared 11,865 patients treated within three hours of stroke with 644 patients who were treated within three-to-four-and-a-half hours, they found that the risk of hemorrhage complications and death was not significantly higher for the second group. The retrospective analysis was published online by The Lancet on Sept. 15 and based on patient data recorded in Safe Implementation of Treatments in Stroke (SITS), a prospective Internet-based audit of the International Stroke Thrombolysis Registry.

The mortality and hemorrhage rates for those receiving tPA within the standard treatment timeframe were 12.2% and 1.6%, respectively, compared with 12.7% and 2.2%, respectively, in the three-to-four-and-a-half hour group. Patients in both treatment groups also exhibited similar outcomes as far as their ability to perform everyday activities three months after stroke; 56.3% for those in the standard treatment group and 58.0% in the extended timeframe group. However, researchers did find a non-significant increased risk of symptomatic intracranial hemorrhage and mortality at three months in patients treated after three hours.

The trial supports efforts to extend the timeframe for thrombolysis, said an accompanying editorial. However, the goal is to eventually move away from the rigid timeframes associated with tPA to treatment based on imaging that can assess brain pathophysiology and tissue viability.

The second study was an industry-sponsored trial published in the Sept. 25 New England Journal of Medicine. In this randomized, double-blind, placebo-controlled trial, researchers at 130 sites in 19 countries randomized a cohort of approximately 800 subjects to placebo or to alteplase (to 0.9 mg/kg) administered at a median of 3 hours and 59 minutes. They found that those treated with alteplase had a 34% improvement in the odds of having a favorable outcome (52.4% vs. 45.2%) compared with those treated with placebo. Patients who had brain hemorrhage or major infarction were excluded from the study.

The incidence of intracranial hemorrhage was higher with alteplase than placebo at 27.0% vs. 17.6% respectively, as well as for symptomatic intracranial hemorrhage at 2.4% vs. 0.2%, respectively. There was no significant difference in mortality between the two groups, with a rate of 7.7% in the alteplase group and 8.4% in the placebo group.

Together, the results of the two studies provide evidence that “withholding thrombolytic treatment [because the three hour window has closed] engenders greater risk than giving it at up to 4.5 hours after symptom onset,” according to commentary in the Journal Watch Emergency Medicine.

Study says drug-coated stents are better than bare-metal stents

Drug-eluting stents appear to be superior to bare-metal stents in patients undergoing coronary-artery stenting for acute myocardial infarction (MI), according to a prospective observational study in the Sept. 25 New England Journal of Medicine. The overall mortality rate among study subjects was 2% lower for patients with drug-eluting stents compared with patients who received bare-metal stents.

Prior studies had been small or had no more than a year of follow-up, so in an effort to access large numbers of subjects with lengthy follow-up, researchers analyzed a state-mandated quality-of-care database that included all percutateous coronary interventions performed at acute care, nonfederal hospitals in Massachusetts. Based on this review of approximately 7,200 patients who underwent coronary-artery stenting for acute MI, researchers found that drug-eluting stents were associated with decreased mortality rates and a reduced need for repeat revascularization procedures. Drug-eluting stents were used in an estimated 55% of the patients, while bare-metal stents were used in the remainder.

Adjusted analysis of matched pairs was used to compare recipients of drug-eluting stents with recipients of bare-metal stents. Three propensity-matched cohorts—all patients with acute MI, all those with acute MI with ST-segment elevation, and all those with acute MI without ST-segment elevation—were grouped based on clinical, procedural, hospital and insurance information.

The 2-year, risk-adjusted mortality rates were lower for drug-eluting stents than for bare-metal stents among all patients with MI (10.7% vs. 12.8%); among patients with MI with ST-segment elevation (8.5% vs. 11.6%); and among patients with MI without ST-segment elevation (12.8% vs. 15.6%). Mortality rates and repeat target-vessel revascularization rates at 2 years were significantly lower with drug-eluting stents. The rates of reinfarction were reduced in patients with MI without ST-segment elevation who were treated with drug-eluting stents. The authors stressed the need for large, long-term, randomized studies to confirm these observational findings.

ICU patients experience higher rate of PTSD

About one in five, or 20%, of intensive care unit (ICU) patients experiences post-traumatic stress disorder (PTSD) symptoms following discharge, according to a literature review published in the September/October issue of the Journal of General Hospital Psychiatry. Experiencing or witnessing life-threatening events, such as serious accidents, violent personal assaults or natural disasters are typical precursors to PTSD.

The review, which comes out of the Department of Psychiatry and Behavioral Sciences at the University of Washington, School of Medicine in Seattle, analyzed 15 previously published studies that comprised data from 1,745 former ICU patients. Researchers reported that being treated in an ICU can set off PTSD symptoms such as nightmares, flashbacks, irritability, anger and emotional detachment, and have negative effects on the patients and their quality of life.

Patients with a history of anxiety or depression were more likely to develop PTSD after an ICU stay, as were ICU patients sedated with benzodiazepine medications and those who recalled alarming ICU treatment experiences after discharge. Studies based on clinician diagnosis found that 19% of former ICU patients developed PTSD symptoms, whereas studies that relied on patient symptom questionnaires found that 22% of ICU survivors developed PTSD symptoms. PTSD symptoms often extend for months or years after the traumatic event and typically affect about 6.8% of the general U.S. population.

Given that about 4 million people per year spend time as ICU patients in the U.S. alone, the prevalence of ICU-associated PTSD represents a significant public health issue, according to the study's lead author. Health care providers can use the results of this review to prepare families of ICU patients for the possibility that their relatives could have problems with anxiety and PTSD symptoms after an ICU stay.

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