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Severe Sepsis Increases Risks for Atrial Fibrillation, Stroke

Publish date: November 18, 2011

Author(s):

Major Finding: Among patients with severe sepsis, those with new-onset AF are at increased risk of in-hospital stroke and mortality.

Data Source: Retrospective population-based cohort of California State Inpatient Database administrative claims for 2007.

Disclosures: The authors had no conflicts to disclose. This study was funded by grants from the Boston University Clinical Translational Research Institute; the Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University; the National Heart, Lung, and Blood Institute; the National Cancer Institute; and the U.S. Department of Veterans Affairs.

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Sepsis and AF: Is Intervention Needed?

Severe sepsis is a major worldwide health problem, with mortality rates of 18%-50%. Severe sepsis occurs in an estimated 50-300 cases per 100,000 individuals annually. Studies about the mortality rate conflict.

When treating a patient with severe sepsis and new-onset AF, the short-term goals are to control the patient’s heart rate and perform cardioversion if the patient is hemodynamically unstable.

Dr. Walkey and colleagues report that patients with severe sepsis and new-onset AF had increased odds of in-hospital stroke and increased hospital mortality

An important question is whether the findings of this study should lead clinicians to intervene with stroke prevention therapy, such as acute cardioversion (a method to restore an abnormal heart rhythm back to normal), or anticoagulation, or both.

However, it is difficult to maintain successful cardioversion as long as severe sepsis persists, perhaps because acute risk factors such as high catecholamine states have not yet resolved. Anticoagulation presents additional risks for patients with severe sepsis resulting from coagulation abnormalities and frequent invasive procedures.

Given the limitations of these observational data, current practice should not change in favor of interventions that could involve additional risk. Further observational studies with large databases are needed to assess how interventions might modify the risk of stroke.

Christopher H. Goss, M.D., of the University of Washington, Seattle, receives grants from Transave Inc., Vertex Pharmaceuticals, the National Institutes of Health, the Food and Drug Administration, and the Cystic Fibrosis Foundation; he receives lecture fees from Roche and Johns Hopkins University; and he participates in advisory board activities for Transave Inc. and KaloBios Pharmaceuticals. Shannon S. Carson, M.D., of the University of North Carolina at Chapel Hill receives consulting fees from Research Triangle Institute. This work was supported by grants from the National Institutes of Health, the Food and Drug Administration, and the Cystic Fibrosis Foundation. These remarks were adapted from an editorial that accompanied the study (JAMA doi:10.1001/jama.2011.1730).

FROM JAMA

Patients who are hospitalized with severe sepsis and experience new-onset atrial fibrillation are at increased risk of in-hospital stroke and death, according to a study published online Nov. 13 in JAMA.

New-onset AF develops in an estimated 6%-20% of patients with severe sepsis (that is, sepsis that occurs during the hospital stay rather than existing at admission), according to Dr. Allan J. Walkey of Boston University and colleagues. This suggests that severe sepsis may be a predisposing factor for new AF, they wrote.

They found that in patients with severe sepsis, in-hospital ischemic stroke occurred in 2.6% of those with new-onset AF, compared with 0.57% of those with preexisting AF. It occurred in 0.69% of patients without AF, the researchers found.

This is meaningful because an estimated 60,000 patients with severe sepsis will likely experience new-onset AF in 2011, the authors calculated. Chronic AF is a known risk factor for stroke and death, but the clinical significance of new-onset AF in patients with severe sepsis is as yet uncertain, they wrote (JAMA 2011 Nov. 13 [doi:10.1001/jama.2011.1615]).

The researchers defined new-onset AF as AF or atrial flutter that occurred during the hospital stay but that was not present at the time of admission. They also defined in-hospital ischemic stroke as not being present at the time of admission. They said there had previously been no population-based assessment of the adverse outcomes associated with the new-onset AF that occurs in those patients who have severe sepsis.

"New-onset AF that occurs during severe sepsis is an underrecognized public health problem."

For their retrospective population-based cohort study, the investigators identified 49,082 cases of severe sepsis identified by the ICD-9-CM code 995.92). In-hospital ischemic stroke occurred in a total of 3,310 adult hospitalizations with and without sepsis.

Overall, inpatients with severe sepsis were nearly seven times more likely than those without to have new-onset AF, the investigators found.

And severe sepsis patients with new-onset AF also had a 17% greater risk of in-hospital mortality than did those without new-onset AF (56% vs. 39%, respectively).

"Current guidelines do not address AF that occurs in the setting of severe sepsis or acute infection, suggesting that new-onset AF that occurs during severe sepsis is an underrecognized public health problem. If our findings of increased stroke and death in the setting of AF and severe sepsis are replicated in other data sets, then it will be important to examine management strategies that might diminish the risk of adverse outcomes associated with AF during severe sepsis," they wrote.

Factors that were associated with increased risk of new-onset AF during severe sepsis include demographics (increasing age, male sex, and white race), comorbidities (history of heart failure, obesity, malignancy, and stroke), and various acute factors (such as increasing number of organ failures, respiratory failure, and renal failure).

Potential mechanisms that might explain the increased ischemic stroke risk in patients with severe sepsis and new-onset AF include hemodynamic collapse, increased systemic inflammation, and coagulopathy. Or, new-onset AF "may simply be a market for greater severity of illness and, thus, greater stroke risk," the researchers wrote.

The mean age of patients studied was 69, 48% were women, and the racial/ethnic composition was 56% white, 20% Hispanic, 9% black, and 15% other/missing. The cohort was drawn from the 2007 California State Inpatient Database of 3,144,787 hospitalized adults for all of that year.

This study has several limitations, its authors wrote. The 5.9% incidence of new-onset AF associated with severe sepsis is on the lower end of the 6%-20% reported rates. And clinicians may not report episodes of AF that they consider to be clinically insignificant. Also, an "immortal time" bias may have occurred, meaning that patients had to survive long enough to be diagnosed with AF. Finally, the administrative data used for this study are limited in ascertaining the timing of clinical events.

The study authors reported having no financial conflicts of interest. This study was funded by grants from the Boston University Clinical Translational Research Institute; the Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University; the National Heart, Lung, and Blood Institute; the National Cancer Institute; and the U.S. Department of Veterans Affairs.