Acute kidney injury (AKI) leading to renal replacement therapy (RRT) occurs in 5 % of intensive care unit (ICU) admissions [1–4]. In most North American ICUs, hemodynamically unstable patients with AKI requiring RRT or those with multiorgan failure are offered CRRT [5–10]. However, CRRT is resource intensive [11, 12] and may not improve outcomes for a subset of critically ill patients with AKI [13].
In particular, some patients who enter the ICU and receive CRRT and other invasive therapies such as extracorporeal membrane oxygenation may not survive more than 24 h. Patients and families often question the likelihood of survival and also the likelihood of renal survival while considering escalation of care, including CRRT [14]. Clinicians engaged in care of patients with AKI needing CRRT recognize high rates of hospital mortality and long-term mortality and low rates of complete renal recovery. This leads to challenging conversations with the families especially in the absence of definite clinical and demographic characteristics that predict early (<24 h) mortality. Lack of conclusive evidence leads to “time-limited” trials of escalation of care. Identification of these characteristics can lead to better-shared decision-making with patients and families and help clinicians frame their goals of care and prognostic discussions in the ICU [14]. Identifying predictors of early mortality with routinely measured laboratory and clinical variables would be of great assistance in appropriately identifying patients who are unlikely to benefit from initiation of CRRT.
Objectives
In order to address this evidence gap, we performed a prospective cohort study in patients with AKI admitted to a tertiary care ICU who underwent CRRT. We were interested in both the natural history of AKI requiring CRRT and in identification of risk factors for early mortality. The primary outcome was as follows: early (24 h) mortality after CRRT initiation. Other secondary outcomes included mortality and renal outcomes post discharge for 90 days.
Design
We conducted a prospective study in the three ICUs (12-bed surgical ICU, 10-bed medical ICU, and a 7-bed combined ICU for both medical and surgical patients) of the Regina Qu’Appelle Health Region (RQHR), Saskatchewan, Canada. The decision to initiate CRRT was made by nephrologists in consultation with intensivists, and ICU nurses implemented CRRT. The indications for starting CRRT were diuretic-resistant clinically significant edema (pulmonary edema), oliguria and/or anuria despite being adequately volume-resuscitated and resistant to diuretic use, hyperkalemia (>6.0 mmol/L), and AKI stages 2 and above on inotropic support. There are seven intensivists and six nephrologists at our site, and the decision was based on individuals rather than standardized criteria.
Patients were started on CRRT using a PRISMA dialysis machine (Hospal Gambro, St. Leonard, PQ, Canada) in continuous veno-venous hemodiafiltration (CVVHDF) mode. The initial prescription was blood flow at 150 mL/min; the dose of CRRT based on the effluent flow rates (the sum of ultra filtrate and dialysate) normalized to body weight was 35 ml/kg/h with pre-filter dilution. ST 100 and 150 filters (Hospal Gambro, St. Leonard, PQ, Canada) were based on body weights of less than or greater than 100 kg, respectively. All patients received citrate regional anticoagulation, and if there were contraindications to its use, then systemic heparin was alternatively administered.
Patients
All patients older than 18 years of age with AKI who entered the ICUs and received CRRT were followed prospectively. Data was prospectively collected from April 2013 to September 2014. The ICU staff informed the study co-coordinator about initiation of CRRT. All patients requiring CRRT during the study period were included. Patients receiving conventional intermittent hemodialysis and patients with AKI stage 3 but not initiated on RRT were excluded. Patients with metastatic cancer and a documented evidence of dementia were not offered CRRT. There were six patients who were not on inotropes but received CRRT; they were included in the study population.
Measurements
We created a case report form for the purpose of the study, and demographic and clinical information were obtained prospectively upon initiation of CRRT. It recorded the following: date and time of hospital admission; date and time of transfer to ICU; date and time of starting CRRT; creatinine at admission and at the start of CRRT; weight on admission to ICU and on starting CRRT; duration of oliguria and anuria prior to starting CRRT; pH values on CRRT initiation; demographics (age, sex, ethnicity); site of vascular access (right internal jugular vein, left internal jugular vein, right femoral vein left femoral vein, right subclavian vein, left subclavian vein); complications post insertion of vascular access; exposures (sepsis, critical illness, circulatory shock, burns, trauma, cardiac surgery, major non-cardiac surgery, nephrotoxic medications, and radio contrast agents); chronic disease comorbidities (congestive heart failure [CHF], hypertension, diabetes mellitus); Acute Physiology and Chronic Health Evaluation II (APACHE II) score; vasoactive support (epinephrine dose, norepinephrine dose, vasopressin dose, dopamine dose, dobutamine dose, milrinone dose); positive-end expiratory pressure (PEEP); fraction of inspired oxygen (FiO2); and extra corporeal membrane oxygenation (ECMO) at the initiation of CRRT. Outcomes such as ICU survival, hospital survival, and renal recovery were also recorded.
Creatinine was recorded daily for the duration of inpatient stay for all patients with AKI until discharge. For patients who had AKI, but not receiving CRRT, creatinine on admission and peak creatinine were documented. AKI was defined as per Kidney Disease Improving Global Outcomes (KDIGO) guidelines into three stages based on the increase of serum creatinine from the baseline (stage 1, 1.5 to 1.9 times the baseline; stage 2, 2.0–2.9 times the baseline; stage 3, >3 times the baseline or increase in serum creatinine to >353 μmol/L or initiation of RRT). Chronic kidney disease (CKD) was defined based on the estimated GFR recording in physician charts and pre-hospitalization creatinine values suggesting CKD as per the modified diet in renal disease (MDRD) formula. Oliguria (as defined by the criteria for AKI) was defined as urine volume of less than 0.5 mL/kg/h for 6 h or 0.3 mL/kg/h for 24 h. Renal recovery at hospital discharge was defined as follows: (1) no recovery if patients continued on RRT, (2) complete recovery if creatinine was less than 26.5 μmol/L above the baseline value, and (3) partial recovery if the creatinine level was at least 26.5 μmol/L higher than the baseline value [15]. Renal recovery, i.e., complete or partial, was assessed at time of hospital discharge. For those discharged without complete recovery of baseline renal function, renal recovery was re-evaluated at 9 months following hospital discharge.
The APACHE II scoring system, a hospital mortality prediction tool, was calculated at the point of starting CRRT, and a score of 0–100 was created for each patient. Our institutional review ethics board (REB) approved the study (REB-12-87). The data was collected confidentially and deindentified.