Abstract

Abstract BACKGROUND AND AIMS In the early stages of sepsis, the renin–angiotensin–aldosteron system (RAAS) is activated despite adequate volume resuscitation. Overactivity of RAAS might contribute to an inferior outcome in patients with severe sepsis, therefore modulation of RAAS could be beneficial in preventing organ failure and reducing mortality. Recommendation to discontinue angiotensin convertase enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) for the prevention of acute kidney injury (AKI) in these patients is currently controversial. In this retrospective cohort study, we aimed to study the potential effect of pre-hospital ACEI or ARB use on the incidence of AKI and mortality in patients admitted to the intensive care unit (ICU) with septic shock. METHOD A total of 536 patients admitted to a single ICU for septic shock during a 5-year period were selected for inclusion in the study. Pre-admission ACEi/ARB exposure was extracted from the admission documents. Propensity score matching based on age, gender, diabetes, hypertension and cardiovascular disease (CVD) was used to control for baseline differences between ACEi/ARB treated and control patients. Stages of AKI were defined according to the KDIGO criteria, using the first available creatinine level as a baseline. Since ACEi/ARB therapy was discontinued after admission, AKI was only considered within the first 3 days of admission. The incidence of AKI stages was compared between treated and control patients. In addition, multivariate logistic regression models were used to assess the association between ACEi/ARB use and mortality in the ICU. RESULTS A total of 241 treated and 274 control patients were identified after matching. The mean age was 71 ± 9 years, 42% were female, the prevalence of diabetes and CVD were 36% and 72%, respectively. As expected, baseline GFR on admission in the treated group was lower compared with control: 37 mL/min versus 49 mL/min; P = .005. The incidence of AKI was similar in both groups: 25 versus 28%; P = .593. The somewhat higher proportion of patients with AKI stage 1 in the treated group (6.6% versus 3.3%) did not reach statistical significance (P = .170). This most likely reflects the glomerular hemodynamic effect of RAS inhibition. The incidence of stage 2 and 3 AKI was comparable in treated (19.1%) and control groups (25.4%, P = .233). Patient survival was similar in both groups: 63.1% versus 58.6%; P = .461. In the whole cohort of 536 patients, only baseline GFR remained an independent predictor of AKI stage 2 or 3 (OR 1.6 for 10 mL/min decline; P < .001) in the multivariate analysis. AKI stage 2 and 3 (OR 3.324; P < .001) and cardiovascular disease (OR 2.288; P = 0.003) were independent predictors of mortality. ACEi/ARB exposure was not associated with patient outcome in our cohort. CONCLUSION In this retrospective cohort study, we confirmed that pre-admission ACEi/ARB use was not associated with a higher risk of AKI in patients with septic shock admitted to the ICU. Our results suggest that ACEi/ARB treatment could be continued until the patient's blood pressure allows in early stages of sepsis.

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