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

Abstract

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.

Keywords: acute kidney injury; coma; critical illness; delirium.

Figure 1.

Patient selection flow diagram. BRAIN-ICU = Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors; eGFR = estimated glomerular filtration rate.

Figure 2.

Predicted probabilities of normal mental status versus delirium versus coma according to acute kidney injury by Kidney Disease Improving Global Outcomes (KDIGO) stage, stratified by mental status on the previous day. After adjusting for demographic factors, nonrenal organ failure, severe sepsis, and the previous day’s mental status and sedative exposure, KDIGO stage was a significant risk factor for delirium and coma. The boxes show that as KDIGO stage rises (i.e., acute kidney injury severity increases), the predicted probability of normal mental status (green) falls, whereas the probabilities of delirium (blue) and coma (red) rise, with the overall probabilities of each mental state also depending on the mental state the previous day. Dashed lines indicate 95% confidence interval boundaries. (A–C) Excludes days where patients were receiving renal replacement therapy (RRT) from stage 3 acute kidney injury. (D–F) Includes all days with and without RRT in stage 3 acute kidney injury.

Figure 3.

Predicted probabilities of normal mental status versus delirium versus coma according to change from baseline in serum creatinine, stratified by mental status on the previous day and by renal replacement therapy (RRT). After adjusting for demographic factors, baseline serum creatinine, nonrenal organ failure, severe sepsis, and the previous day’s mental status and sedative exposure, an increase in serum creatinine was a significant risk factor for delirium and coma. The solid lines show that as daily peak serum creatinine increases among patients not on RRT (A–C), the predicted probability of normal mental status (green) falls, whereas the probabilities of delirium (blue) and coma (red) rise, with the overall probabilities of each mental state also depending on the mental state the previous day. Alternatively, change in daily peak serum creatinine among patients on RRT (D–F) has no significant association with the predicted probability of mental status. Dashed lines indicate 95% confidence interval boundaries, and box plots on the x-axis indicate the distribution of peak serum creatinine (medians with interquartile range) according to previous day’s mental status and use of RRT.