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June - 2017


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Acute Kidney Injury as a Risk Factor for Delirium and Coma during Critical Illness

E Siew, W Fissell, C Tripp, J Blume, et al Am J Resp Crit Care Med, 2017, 195(12);1597-1607


We know acute kidney injury and acute brain dysfunction are associated with both short and long term morbidity and mortality. Is it possible that AKI can contribute to brain dysfunction, i.e. delirium and coma?

This study examined the relationship between AKI and cognitive dysfunction as a secondary analysis of the BRAIN-ICU (Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors) study, a multicenter, prospective cohort study of critically ill adults with daily assessments of both kidney and neurologic function.

What did they do and find;

  • Analysed 466 patients with acute respiratory failure and/or shock (cardiogenic or septic), and classified by KDIGO acute kidney injury Stages. Baseline renal function was normal for most patients
  • Overall incidence of AKI during the 30 days after enrollment was 65% with;
    • >50% of patients having moderate-to-severe kidney injury
    • 10% received renal replacement therapy. Of these 68% received their initial renal replacement therapy during the study period, 62% CRRT or SLED, 38% IHD
  • Delirium and coma as outcomes were assessed twice daily in ICU, then daily until discharge;
    • 75% experienced delirium at least once
    • 60% experienced coma at least once
    • 47% both
    • Mental status was normal for 2672 (53%) of 5056 patient-days, 32% delirium, 15% comatose
  • Association between AKI and delirium/coma
    • AKI present 37% study days when patient had normal mental status, 50% days when patient delirious, 65% days when patient comatose
    • After adjusting for demographic factors, non-renal organ failure, severe sepsis, previous day’s mental status and sedative exposure, acute kidney injury was a risk factor for both delirium and coma during non–renal replacement therapy days.  Specifically, compared with no acute kidney injury;
      • Odds of delirium increased in the setting of KDIGO stage 2 (OR, 1.6; 95% CI, 1.1–2.3) and KDIGO stage 3 (OR, 2.6; 95% CI, 1.6–4.2).
      • Odds of coma increase in stage 2 (OR 2.0, 95% CI 1.3-3.3) and 3 (OR 3.3, 95% CI 1.9-6.0)
      • RRT attenuated this relationship. This included the finding that AKI as measured by peak serum creatinine was a risk factor for delirium and coma in patients not receiving RRT (OR 1.35, OR 1.44), but not in patients receiving RRT (OR 1.07, 1.16).

This prospective cohort reports an association between moderate to severe AKI and delirium and coma, a relationship that was modified by RRT. This is a plausible finding, although it is single centre, and a cohort study, so residual confounding and external validity are issues. However it is interesting, and raises the need for future studies to explore mechanisms, validate findings, and test the relationship of modifying delirium and coma through the use of interventions such as RRT.



Rationale: Acute kidney injury may contribute to distant organ dysfunction. Few studies have examined kidney injury as a risk factor for delirium and coma.

Objectives: To examine whether acute kidney injury is associated with delirium and coma in critically ill adults.

Methods: In a prospective cohort study of intensive care unit patients with respiratory failure and/or shock, we examined the association between acute kidney injury and daily mental status using multinomial transition models adjusting for demographics, nonrenal organ failure, sepsis, prior mental status, and sedative exposure. Acute kidney injury was characterized daily using the difference between baseline and peak serum creatinine and staged according to Kidney Disease Improving Global Outcomes criteria. Mental status (normal vs. delirium vs. coma) was assessed daily with the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale.

Measurements and Main Results: Among 466 patients, stage 2 acute kidney injury was a risk factor for delirium (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.07–2.26) and coma (OR, 2.04; 95% CI, 1.25–3.34) as was stage 3 injury (OR for delirium, 2.56; 95% CI, 1.57–4.16) (OR for coma, 3.34; 95% CI, 1.85–6.03). Daily peak serum creatinine (adjusted for baseline) values were also associated with delirium (OR, 1.35; 95% CI, 1.18–1.55) and coma (OR, 1.44; 95% CI, 1.20–1.74). Renal replacement therapy modified the association between stage 3 acute kidney injury and daily peak serum creatinine and both delirium and coma.

Conclusions: Acute kidney injury is a risk factor for delirium and coma during critical illness.


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