In this before-and-after study, we examined whether CERTAIN based on sepsis and KDIGO care bundles targeted at prevention of AKI on patients with septic shock. This study showed that the use of CERTAIN as a screening and treating tool reduced the ratio of AKI in patients with septic shock, especially the rate of moderate to severe AKI in the Post-CERTAIN group. Moreover, the patients who were managed with CERTAIN had a lower proportion of mortality and rate of MAKEs within 90 days.
Whether KDIGO care bundles improve the short or long outcomes of critically ill patients is inconsistent due to the heterogeneity of AKI. Previously, Koeze et al. discovered that care bundles focusing on KDIGO 2012 had no beneficial effect on critically ill patients when evaluated the ICU mortality, RRT dependency, and AKI progression.19 However, our data indicated that implementation of CERTAIN focusing on sepsis 3.0 and KDIGO bundles can reduce the occurrence of AKI, mortality, and incidence of MAKEs within 90 days of patients with septic shock. These results are consistent with the studies that evaluated KDIGO care bundles in patients after cardiac surgery and major surgery.14,20,21
It is noteworthy that the implementation of the Surviving Sepsis Campaign and KDIGO care bundles improved the short- and long-term outcomes of sepsis and AKI, respectively.22, 23 However, in clinical practice, these interventions have been shown to have poor performance. Bundle fatigue was one of the main issues affecting their implementation.24 Moreover, in the absence of sufficient support for decision making and the inappropriate selection of medical interventions, medical errors are the leading cause of death in hospitals.25, 26 In this study, CERTAIN was associated with improvement of eight of 10 practices of the KDIGO care bundles. The compliance of the crucial practices may influence the prognosis of the patients, as the higher adherence to active measures has been shown great benefits of care bundles.27 Recently, a multicentre international study showed that CERTAIN improved daily care processes in ICU, especially in low- and middle-income countries.28 Care bundles in the form of a list combined with an electronic warning could improve the compliance of medical staff to evidence-based guidelines, minimize medical errors and improve outcomes in ICU.29 The high adherence of care bundles after CERTAIN training was associated with improvement in the treatment of patients with septic shock.
Fluid resuscitation and vasoactive agents are cornerstones in the treatment of both septic shock and AKI.15, 16 Fluid challenge should be evaluated between the balance of increasing in oxygen delivery to tissues and inhibiting of edema formation.30 In contrast to the Pre-CERTAIN group, all the patients in the Post-CERTAIN group were evaluated for fluid responsiveness, then monitored CVP during the following fluid management. CVP is not an accurate indicator to predict fluid responsiveness, but CVP is the most frequently used and most easily obtained variable to guide fluid resuscitation in ICU.31 Single CVP value cannot differentiate responder from nonresponder. However, the changing of CVP during fluid bolus may predict responsiveness. Thus, patients in the Post-CERTAIN group were given 200-500mL crystalloid fluid within 10–15 minutes. If CO and SV detected by transthoracic Doppler increased by 10%-15% with a rise in CVP < 5mmHg indicates good tolerance to fluids, whereas an increase in CVP ≥ 5mmHg indicates poor tolerance to fluids.31 To inhibit delayed resuscitation and fluid overload, this study used changes in CVP during fluid challenge together with changes in CO to predict fluid responsiveness.31 In addition, CVP maintained to 8-12mmHg as the following target as the majority of patients respond to fluids.32 The increased use of noradrenaline and de-escalation fluid resuscitation in the Post-CERTAIN group maintained a better haemodynamic stabilization and tissue perfusion.
The pathophysiology of SA-AKI is complicated. Surviving Sepsis Campaign care bundles showed no reduction in the incidence of AKI within the first week after the development of sepsis.33 We implemented a bundle of supportive measures which are recommended by sepsis and KDIGO guidelines. The multifactorial measures may reduce the occurrence of AKI after septic shock. SA-AKI is associated with increased morbidity and mortality. Our findings were in line with goal-directed therapy in a reduction of mortality and MAKEs.34 However, the PreAKI study showed that the implementation of the KDIGO guidelines had no impact on mortality and MAKEs at day 90. That might be due to the different eligible patients. We assumed that the positive effect of the CERTAIN checklist on reducing the incidence and severity of AKI, decrease in mortality, and MAKEs at day 90 was caused by optimal fluid resuscitation with de-escalation fluid management and kidney protection.
Our study has several limitations. First, it was a single-center study of patients with septic shock may limit the generalizability of its results. Second, this study was not blinded, which resulted in measurement bias. Third, the Hawthorne effect was the confounding factor in before-after studies. Further trials with a larger multicenter cohort of patients with septic shock are warranted.