Journal watch: Recent studies of note

Recent studies about norepinephrine use in septic shock, desmoteplase vs. placebo use in stroke, and other topics.


Norepinephrine may worsen outcome in septic shock

Norepinephrine may lead to worse outcomes in patients with septic shock, a study has reported.

Portuguese researchers performed a multicenter observational study to determine how the choice of a vasopressor agent affected mortality in patients with septic shock. Eight hundred ninety-seven patients with sepsis from 17 Portuguese ICUs were studied, 458 of whom had septic shock. The results appeared in the February Critical Care Medicine.

Seventy-three percent of patients with septic shock received norepinephrine and 50.5% received dopamine. Mortality rates were higher in the former group (52% vs. 38.5%; P= 0.002), as was the risk for death (adjusted hazard ratio, 2.501 [95% CI, 1.413 to 4.425]; P= 0.002). A trend toward increased 28-day mortality was observed in the norepinephrine group while a trend toward decreased 28-day mortality was seen in the dopamine group.

The study had several limitations, including its nonrandomized design. However, the authors concluded that norepinephrine may be associated with worse outcome in patients with septic shock and suggested that dopamine may be a better first-line choice. They called for a randomized, controlled trial to further evaluate this question.

Desmoteplase, placebo no different three to nine hours after stroke

Acute ischemic stroke patients who were given desmoteplase three to nine hours after stroke onset had no better response rates than patients given placebo, a study in the February Lancet Neurology found.

While alteplase within three hours of onset is the only approved treatment for acute ischemic stroke, two previous studies suggested desmoteplase may work up to nine hours after onset. To confirm the earlier results, researchers randomly assigned 186 acute ischemic stroke patients to 90 µg of desmoteplase per kg, 125 µg of desmoteplase per kg, or placebo within three to nine hours after onset of stroke symptoms. The primary endpoint was clinical response rate at day 90, defined by a composite of scores on several stroke scales.

The clinical response rates at day 90 were 47% for patients who got 90 µg of desmoteplase per kg, 36% for those who got 125 µg of desmoteplase per kg, and 46% for those who got placebo. As for secondary endpoints, the median change in lesion volume between baseline and day 30 was 14% for those in the 90-µg group, 11% for those in the 125-µg group, and 10% for those in the placebo group. The rates of symptomatic intracranial hemorrhage were 3.5% for the 90-µg group, 4.5% for the 125-µg group, and 0% for the placebo group. Overall mortality was 11% for the 90-µg group, 21% for the 125-µg group, and 6% for the placebo group.

Results showed no benefit of giving desmoteplase three to nine hours after stroke onset. The placebo group may have showed a high response rate due to the mild strokes that were recorded, which may also have reduced the potential to detect an effect from desmoteplase, the study's authors said.

Tool helps assess pneumonia severity in the ICU

A new prediction rule may help in assessing ICU patients with pneumonia, a study has reported. Researchers aimed to develop a new scoring tool to assess disease severity and mortality risk in patients with community- acquired pneumonia (CAP) admitted to the ICU. Five hundred twenty-nine patients at 33 ICUs were used to develop the score. A detailed report appeared in the February Critical Care Medicine.

Researchers used the PIRO concept (predisposition, insult, response and organ dysfunction) to develop the score. Within 24 hours of ICU admission, patients were given one point for the presence of each of the following:

  • comorbid conditions (chronic obstructive pulmonary disease, immunocompromise),
  • age older than 70 years,
  • multilobar opacities on chest radiography,
  • shock,
  • severe hypoxemia,
  • acute renal failure,
  • bacteremia, and
  • acute respiratory distress syndrome.

Zero to two points was considered low risk, three points was considered mild risk, four points was considered high risk, and five to eight points was considered very high risk. Higher PIRO scores were associated with higher mortality rates, longer ICU stay, and days of mechanical ventilation (P<0.001 for all). PIRO score predicted 28-day mortality better than APACHE II score and American Thoracic Society/Infectious Diseases Society of America criteria (area under the receiver-operating characteristic curve, 0.88, 0.75, and 0.80, respectively).

The authors concluded that the PIRO score offers a simple and effective way to predict disease severity and health care utilization in patients with CAP in the ICU. They called for additional studies to validate the score in different populations and for other outcomes, such as 90-day mortality rate.

Acute geriatric units may improve functional outcomes, study finds

Elderly patients cared for in acute geriatric units functioned better after their hospital stay than those who received conventional care, according to a recent study.

Spanish researchers performed a meta-analysis to determine whether acute geriatric units could improve outcomes in elderly patients admitted to the hospital. The authors assessed functional decline, living at home and case fatality both at hospital discharge and three months. The results were published in the February 7 BMJ.

Of 11 trials reviewed, five were randomized. Meta-analysis of these trials showed that elderly patients in acute geriatric units were less likely to have functional decline at hospital discharge (combined odds ratio, 0.82 [95% CI, 0.68 to 0.99]) and more likely to be discharged home (combined odds ratio, 1.30 [CI, 1.11 to 1.52]) than elderly patients receiving conventional care. Patients cared for in acute geriatric units were also more likely to be living at home three months after hospital discharge. Case fatality rates, meanwhile, were similar between the two groups (combined odds ratio, 0.83 [CI, 0.60 to 1.14]).

The authors acknowledged the limitations of their trial, including the small number of studies analyzed, but concluded that acute geriatric units offer benefit to elderly hospitalized patients. “Research should focus on the impact of acute geriatric units on functional decline in the medium term and should try to identify the specific activities associated with this effect,” they wrote.

Quick stroke therapy reduces cost and disability

Urgent assessment and treatment of transient ischemic attack (TIA) or minor stroke can reduce hospital admissions, costs and disability, according to recent study data.

The EXPRESS study, a prospective population-based sequential comparison conducted in England, had already found that early treatment reduced the 90-day risk of recurrent stroke. The study had two phases, one in which patients with TIA were referred by their primary care physicians to appointment-based outpatient clinics that sent treatment recommendations back to the physicians. In the second phase, patients received immediate assessment and treatment at the clinic. The study was published online by The Lancet Neurology on February 5.

Patients treated in the second phase had fewer hospital admissions for recurrent stroke (5 vs. 25) and fewer inpatient days due to vascular causes (427 vs. 1,365). They also had shorter overall length of stay and were less likely to be disabled six months after the event. Based on the data, researchers concluded that urgentcare clinics offering treatment for TIA and minor stroke could be cost-effective, reducing hospital and disability costs.

However, the trial did not include the cost of setting up such clinics, and study authors recommended that follow-up be done to determine the long-term cost-effectiveness. Despite that concern, the authors of an accompanying editorial argued that the study provides sufficient evidence to put the research into practice and treat TIA urgently.

Model helps predict rare cause of community-acquired bacteremia

Researchers developed a model that may help hospitalists predict and treat a rare bacterial infection that can cause community-acquired bacteremia in patients with severe immunodeficiency.

In the retrospective study at four tertiary care hospitals, researchers examined data from 151 patients with P. aeruginosa bacteremia and 152 randomly selected patients with bacteremia due to Enterobacteriaceae. P. aeruginosa, which caused 6.8% of 4,114 unique patient episodes of gram-negative bacteremia upon admission, had several independent predictors, including severe immunodeficiency, age more than 90 years, receipt of antimicrobial therapy within the last 30 days, and presence of a central venous catheter or a urinary device.

Researchers found that the risk of having P. aeruginosa bacteremia went up if patients had at least two predictors. If no predictors existed, the risk of having P. aeruginosa was 1:42 but the risk increased to 1:3 if two predictors existed. The study is in the March 1 issue of Clinical Infectious Diseases.

Researchers concluded that empirical anti-pseudomonal treatment is warranted for immunocompetent patients with suspected gram-negative bacteremia and at least two predictors. The findings may help physicians limit unnecessary use of anti-pseudomonal agents without delaying appropriate therapy.