Interaction of acute heart failure and acute kidney injury on in-hospital mortality of critically ill patients with sepsis: A retrospective observational study
Type of article: Clinical Research Summary
MedED Catalogue Reference: MPECS010
Category: Critical Care | Acute Renal Failure | Acute Heart Failure
Category Tags: ICU, Critical Care, Sepsis, AKI, kidney, AHF, heart failure, mortality
Source: PlosOne
Key Take Aways
1. Concomitant AHF in patients with severe sepsis or septic shock and had a 75% death rate 1-year post-discharge
2. AKI occurs in 40–50% of septic patients and increases mortality six-fold
3. Patients with both AHF and AKI in the ICU setting, displayed an elevated risk of in-hospital mortality as compared to those patients who had only one complication
5. The risks of two complications exceeded the sum risk of AKI only and AHF only
6. AHF and AKI had a strong synergic impact on in-hospital mortality in critically ill patients with sepsis
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Overview | Objectives | Study Design,Method & Management | Findings | In Summary | Conclusion
This is a summary of an original research article, reproduced under Creative Commons Attribution-NonCommercial 4.0 International License. It in no way replaces the original work, which has been linked below.
Overview
In this retrospective, observational analysis by researchers Hu et al., the effects of acute kidney injury (AKI) and acute heart failure (AHF) on in-hospital mortality in critically ill patients with sepsis were examined. The major cause of death and morbidity in critically ill patients is sepsis and septic shock, with as many as half of all affected patients dying.
Preexisting heart failure (HF) in patients with sepsis is associated with a 75% death rate 1-year after discharge, whilst sepsis-induced AKI occurs in 40-50% of sepsis patients, resulting in a 6-fold increased mortality rate.
While both AKI and AHF increase the risk of death in severe sepsis patients, it is unclear whether both act synergistically to increase the risk of in-hospital mortality.
Objectives
The researcher’s stated objective was as follows:
“The present study intended to obtain data extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and eICU Collaborative Research Database (eICU-CRD), two large public databases to clarify the interaction effect of AHF and AKI on in-hospital mortality in critically ill patients with sepsis
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Study Design, Methods & Measurements
Key Endpoints
In-hospital mortality was the primary end-point for the study.
Investigative subgroup analyses were done in various subgroups to further validate the interaction effect of AKI and AHF on in-hospital mortality.
Methods
The study used data extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and eICU Collaborative Research Database (eICU-CRD). A Cox proportional hazards model was used to assess the effects of AKI and AHF on in-hospital mortality.
Participant Selection
All patients older than 16 years who were diagnosed at their first admission to ICU with sepsis were included.
The following patients were excluded from the sample group:
- Those younger than 16 years old.
- ICU stay less than 24 hours.
- Repeated ICU hospitalizations.
A total of 33,184 critically ill sepsis patients were included in the study:
- 20,626 patients from the MIMIC-IV database were allocated to the training cohort.
- 12,588 patients from the eICU database were assigned to the validation cohort.
Data Selection
The patients were divided into four groups: those who had neither AKI nor AHF; those who had AKI only; those who had AHF only, or those who had both AKI and AHF.
The AHF diagnosis was based on the International Classification of Diseases (ICD) code and AKI is according to KDIGO-AKI criteria.
In addition to admission and baseline information, length of hospital stay and the following severity scores were collected:
- Sequential Organ Failure Assessment (SOFA)
- Oxford Acute Severity of Illness Score (OASIS)
- Acute Physiology Score III (APSIII)
Related Content | Learn More
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. (2016) 315(8):801–10. https://doi.org/10.1001/jama.2016.0287
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Findings
Hu et al, reported that the overall in-hospital mortality was 14.4% in the training cohort and 17.9% in the validation cohort. Specifically, they noted the following:
Of the 20,626 sepsis patients in the training cohort:
- 5,187 (25.1%) patients had AKI, with in-hospital mortality of 23.5%
- 1,706 (8.3%) patients had AHF, with in-hospital mortality of 11.5%
- 1,452 (7.0%) patients had both AKI and AHF, with in-hospital mortality of 48.3%
- 12,281 (59.6%) patients had neither AKI nor AHF with in-hospital mortality of 7.0%
Of the 12,558 sepsis patients in the validation cohort:
- 2,964 (23.6%) patients had AKI, with in-hospital mortality of 31.0%
- 946 (7.5%) patients had AHF, with in-hospital mortality of 19.3%
- 504 (4.0%) patients had both AKI and AHF, with in-hospital mortality of 59.5%
- 8,144 (64.9%) patients had neither AKI nor AHF, with in-hospital mortality of 9.2%
Those critically ill sepsis patients complicated with both AKI or AHF had the worst overall survival rate and prognosis - 39% chance of in-hospital death - when compared with those complicated with only one complication or neither, as seen in both the training cohort and the validation cohort. The subgroup analysis further validated the impact of AKI and AHF on in-hospital mortality.
In Summary
Both AKI and AHF are often seen as consequences of sepsis in critically ill patients, either complication increasing the risk of death. Many cases were included from the two databases, in addition to a subgroup analysis to validate the interactive effects of AKI and AHF on in-hospital mortality in critically ill patients with sepsis.
The findings indicated that a single condition was related to an increased risk of in-hospital mortality; the addition of a second difficulty exhibited substantial positive additive effects, giving evidence for interactions between these conditions.
Researchers have previously studied the synergistic effects of various complications, such as acute respiratory failure (ARF), which have shown that an extra complication would synergistically increase the mortality risk.
The underlying processes driving the synergistic combination of AKI and AHF may be due to the interaction between kidney and heart in sepsis-induced cytokine release syndrome (CRS). Elevated inflammatory markers and free radicals produce endothelial calcification and dysfunction in a sepsis state, resulting in poor perfusion of the heart and kidneys and therefore more prone to chronic renal and cardiac damage.
Intravenous fluids used during resuscitation may lead to excessive fluid, causing visceral oedema and abdominal or kidney intra-capsular compartment syndrome, with renal blood flow declining and fluid overload having a direct influence on the deteriorating cardiac function by raised cardiac filling pressures.
Hu et al., note that more than half of the patients in this study did not have brain natriuretic peptide (BNP) values which are important for the diagnosis of AHF, and this is an important limitation of the study. Furthermore, the research was a retrospective analysis based on two public databases, future prospective studies or randomized controlled trials should further validate these findings.
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Conclusion
The authors conclude that their results validate the hypothesis that AKI and AHF increase the risk of in-hospital mortality in critically ill patients with sepsis, but when a patient has both conditions together, the mortality risk surpasses the total risk of each individual complication indicating a synergistic relationship of AHF and AKI.
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