In this prospective observational study, we demonstrate a high incidence of new-onset AF in septic shock patients. Remarkably, 46% of all patients with septic shock developed new-onset AF. Among surviving septic shock patients, those who developed new-onset AF had a prolonged ICU stay in comparison to septic shock patients with maintained SR. Further, septic shock patients with new-onset AF may have a poorer prognosis. In the present study, we found a trend towards an increased mortality during a two-year follow-up, but the difference was not statistically significant.
Overall, incidence of new-onset AF in our study was 7.8% (49/629), which is in the range of previous studies (1.8 to 10%) performed in noncardiac ICUs [5
]. However, many of these studies did not clearly focus on AF but rather on a broad variety of atrial arrhythmias. Moreover, in older studies, the patients were not continuously monitored [12
]. Seguin and colleagues exclusively looked at AF on a surgical ICU and found an incidence of new-onset AF of 5.3% [5
]. Thus, our study confirms that new-onset AF is a common complication in critically ill patients. In agreement with previous studies, we found that in two-thirds of the patients, new-onset AF occurred within the first three days on the ICU [5
Salman and colleagues retrospectively analysed patients with sepsis and reported an incidence of AF of 31% [15
]. With respect to the incidence of new-onset AF in septic shock, Seguin and colleagues included a subgroup of 23 patients and observed new-onset AF in 30%, which is slightly lower when compared with our finding of 46% [5
]. One reason for this difference might be our restrictive definition of septic shock, in particular the requirement of vasopressor therapy with norepinephrine for more than five hours with a dosage more than 0.1 μg/kg/min.
In the present study, septic shock patients with new-onset AF were older, more frequently revealed a history of hypertension and developed a higher maximal SOFA score during ICU stay in comparison to septic shock patients with maintained SR. Age and a history of hypertension have been identified in previous studies as risk factors for the development of AF in non-selected ICU patients [5
]. The higher SOFA score in septic shock patients with new-onset AF indicates that presumably there is an association between severity of illness and the development of AF.
A variety of further factors including pre-existing heart failure, ischemic heart disease, valvular disease, electrolyte disturbances and use of catecholamines have been addressed as potential co-factors or causes for the development of new-onset AF in critically ill patients [5
]. In the current study, only a small number of patients developing new-onset AF revealed pre-existing heart failure, ischemic heart disease or valvular disease. Furthermore, we did not find apparent electrolyte disturbances when new-onset AF occurred. Also, regarding the treatment with catecholamines there was no significant difference between septic shock patients with new-onset AF in comparison to those with maintained SR. The present data do not support the hypothesis that one of these factors plays a mayor role in the development of AF in critically ill patients.
The pathophysiological mechanism underlying the development of AF in critically ill patients and in particular in septic shock is not known. However, there is increasing evidence that the systemic inflammatory response per se
is a predominant trigger of AF in critically ill patients. The occurrence of AF after cardiac surgery has been shown to be closely related to the complement CRP activation on the postoperative day two or three [16
]. Also, in the non-operative setting, a series of studies has now demonstrated an association of elevated CRP levels with the development and maintenance of AF [17
]. Chung and colleagues found two-fold higher CRP levels in patients with AF than in control subjects. Furthermore, patients with persistent AF had higher CRP levels than those with paroxysmal AF, suggesting that inflammation plays an important role in the maintenance of AF [17
]. In addition, elevated CRP levels have been correlated to a decreased success rate of electrical cardioversion and subsequent maintenance of SR [20
]. The hypothesis, that inflammation may trigger the development of AF in critically ill patients, is supported by our observation of increasing CRP plasma concentrations before the onset of AF in septic shock patients. Also, in AF patients without septic shock, CRP levels were very high when AF occurred. However, maximal CRP levels occurring during ICU stay did not differ between septic shock patients with new-onset AF and septic shock patients who maintained SR, indicating that other factors may contribute to the development of AF in critically ill patients.
Although new-onset of AF, as reemphasized by the present data, is a frequent and major problem in ICU patients, no evidence-based data regarding the treatment of AF for this patient group are available. In the current study, restoration of SR was possible in 85% of the patients. In the majority of patients, amiodarone was used, but was frequently combined with electrical cardioversion or other drugs. On the other hand, in 12 patients, restoration of SR was possible without the use of amiodarone. Although amiodarone seems to be an effective drug for restoration of SR, we do not know whether the outcome is positively affected by this measure. Previous studies on AF in non-critically ill patients have impressively demonstrated that restoration of SR patients does not automatically imply an improvement in clinical outcome [23
]. Furthermore, prophylactic intravenous administration of amiodarone for supraventricular tachyarrhythmias after pulmonary surgery has been associated with an increased risk for the development of acute respiratory distress syndrome [25
]. Therefore, prospective randomized controlled studies are necessary to evaluate the use of amiodarone in critically ill patients.
The present study contains several limitations. Presumably, the number of patients was too low to demonstrate a significant association between new-onset AF and mortality rate in septic shock patients. Further, due to the limited number of patients, it was not possible to perform a multivariate analysis to identify independent risk factors for the development of AF in septic shock patients. Moreover, therapy of AF was not performed according to a fixed protocol. Therefore, the failure rate to restore SR has to be appraised with caution.