*6.2.5 Anticoagulation therapy*

While many clinical trials have shown that warfarin therapy reduces the risk of thromboembolic complications in patients with AF, it has not been unequivocally proved that oral anticoagulants provide similar benefits in critically ill septic patients with AF without carrying a significant bleeding risk. So, a common dilemma arises when deciding which septic patients with AF should receive anticoagulation therapy [71]. Walkey et al. [72] studied the practice patterns of anticoagulation in 38,582 septic patients with AF. They found that more than a third (35.3%) of the patients were anticoagulated with intravenous heparin or subcutaneous enoxaparin, while the rest of the patients did not receive anticoagulants. In those who did, significant bleeding was more frequently observed (8.6% vs. 7,2%, RR 1.21). Interestingly, there was no significant difference in the risk of ischemic stroke between anticoagulated and non-anticoagulated patients (1.4% vs. 1.3%, RR 0.94, CI 0.78–1.12). Furthermore, there was no difference in the risk of ischemic stroke between patients with preexistent AF and those with NOAF (RR, 1,12).

In a retrospective observational study to assess the incidence of stroke and anticoagulation-related complications (e.g., bleeding, heparin-induced thrombocytopenia) in AF patients with severe sepsis (n = 115), Darwish et al. [71] found no statistically significant difference in survival rates during their hospitalization (66.2% [53/80] in the non-anticoagulated group versus 74.3% (26/35) in the anticoagulated group, P = 0.392). There were no reports of strokes in either arm of the study, but this finding is at least in part explained by the small number of patients and the short period of time used for assessment. Up to date, prospective, comparative robust evidence for anticoagulation in septic shock patients is lacking.

## *6.2.6 Corticosteroid therapy*

Due to its anti-inflammatory properties, low-dose hydrocortisone has been frequently used to achieve shock reversal and better outcomes in patients with septic shock [73]. However, after extensive review of the available evidence, the Surviving Sepsis Campaign's guidelines restricted the use hydrocortisone in shock septic patients only when fluid resuscitation and vasopressor drugs failed to restore hemodynamic stability [74]. In a recent multicenter, prospective nonrandomized observational study in 261 septic shock patients, Launey et al. [75], a atrial fibrillation developed in 33 (24%) and 24 (19%) of no-hydrocortisone patients and hydrocortisone patients, respectively. In the weighted sample, the proportion of patients who developed AF was 28.8% in the nohydrocortisone group and 16.8% in the hydrocortisone group (difference: 11.9%; 95% confidence interval: 23.4% to 0.5%; p = 0.04), noting that patients who received hydrocortisone were more severely ill than those who did not receive hydrocortisone. Investigators conclude that low-dose hydrocortisone was associated with a lower risk of developing AF during the acute phase, although serious risk of bias due to missing covariates in the propensity score matching has to be taken into account.
