“Incidence, predictors, and outcomes of new-onset atrial fibrillation in critically ill patients with sepsis,” AJRCCM, 2017, Netherlands

Question: What is the incidence of new-onset atrial fibrillation/atrial flutter (AF) in ICU patients with sepsis and is the development of AF associated with mortality?

Study Type: Sub-study of a prospective cohort study at two hospitals in the Netherlands

Study Population: Adults admitted to the ICU with sepsis over a two-year period were included.  Exclusion criteria included a history of AF, recent cardiotomy, or cardiac arrest.

Study Groups: AF detection based on hourly recordings of the rhythm observed by the bedside nurse.  AF needed to be sustained for 1 hour or require pharmacologic treatment or cardioversion to be included.

Primary Outcome: Incidence of new-onset AF

Results: 1,782 patients included in analysis.  Notable patient characteristics: Age (»62), immunosuppression (26%), malignancy (10%), lung as source of infection (62%), mechanical ventilation (83%), surgical admission (23%), 90-day mortality (34%).  The overall incidence of AF was 23%.  For patients with septic shock, the risk of AF was 40%.  The most common treatments administered were amiodarone (71%), magnesium (69%), electrical cardioversion (11%), and sotalol (8%).  After multivariable regression, AF remained associated with ICU mortality (HR 2.10; 95% CI, 1.61-2.73).  An AF risk score was developed (the “SAFE” score) and validated in an independent cohort.  The score can be accessed here: https://safescore.shinyapps.io/safe/.

Caveats: Unmeasured confounding a concern in observational studies, unable to prove AF has causal role in poor outcomes, relied on identification and classification of arrhythmia by bedside nurse so possible missed or misclassified episodes, data collected from only two centers.

Take-home Point: New-onset AF is common in ICU patients with sepsis and may lead to increased mortality.

Commentary 

–        Part of a growing body of literature helping to describe the incidence and significance of new-onset AF in critical illness.  Certainly notable that the incidence of AF in septic shock approaches 50%

–        The SAFE score still needs to be independently validated, but it is an interesting attempt by the authors to come up with a way to predict the development of sepsis-induced AF (and, in doing so, potentially identify a group of septic patients to enroll in trials of AF prophylaxis).​

“The timing of early antibiotics and hospital mortality in sepsis” AJRCCM, 2017, USA

Question: Does the timing of antibiotic administration in patients presenting with sepsis impact mortality?

Study Type: Retrospective study of a large healthcare database

Study Population: Adult patients presenting with sepsis (defined by ICD 9 codes + the receipt of abx within 6 hours of ED registration) to any of the 21 hospitals in the Kaiser Permanente Northern California system between 7/2010 and 12/2013.

Study Groups: Septic shock defined as need for vasopressors or initial serum lactate ³4; severe sepsis as a lactate ³2, ³1 instance of hypotension, need for invasive or non-invasive ventilation, or laboratory-determined organ dysfunction; all other patients classified as having sepsis. All vital signs obtained during the first hour were recorded and averaged. Abx administration calculated from the time of ED registration to the administration of the first abx in hours. Logistic regression was used to estimate the odds of hospital mortality based on abx timing and patient factors.

Primary Outcome: Hospital mortality

Results: 35,000 patients randomly selected. Notable patient characteristics: sepsis (35%), severe sepsis (52%), septic shock (13%), median age (73), mean first lactate (1.8), mechanical ventilation (1.4%), mortality of entire group (9.4%), mortality of patients with sepsis (3.9%), mortality of patients with severe sepsis (8.8%), mortality of patients with septic shock (26%). The fully adjusted odds ratio for hospital mortality based on abx timing was 1.09 (95% CI, 1.05-1.13) per elapsed hour after ED presentation. The absolute increase in mortality associated with a 1-hr delay in abx administration was 0.3% (95% CI, 0.01%-0.6%) for sepsis, 0.4% (95% CI, 0.1%-0.8%) for severe sepsis, and 1.8% (95% CI, 0.8%-3%) for shock.

Caveats: Retrospective, only able to describe an association not prove causation, no data provided on other aspects of early resuscitation which may impact outcome (IVF, did abx given cover causative pathogen, etc), only included patients presenting to the ED not patients who develop sepsis while hospitalized, relied upon ICD 9 codes to identify patients with sepsis.

Take-home Point: Among patients presenting to the ED with sepsis, severe sepsis, and septic shock, delays in abx administration are associated with increased mortality.

Commentary 

–        The most frequently cited paper on this subject is by Kumar (CCM, 2006) which retrospectively analyzed 2,731 patients with septic shock and found that for each hour delay in appropriate abx therapy after the onset of hypotension, mortality increased by 7.6%.

–        The result is less dramatic here (1.8% increase for each hour delay in patients with shock) and the authors highlight several methodological differences which may account for their findings.

–        The study has flaws, but it perhaps provides a more accurate look at the true mortality benefit of early abx in the modern era of sepsis management.