Suvi T. Vaara

Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study

IntroductionPositive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality.MethodsWe conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality.ResultsWe included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT.ConclusionsPatients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments.

Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study

IntroductionKnowledge of the association of hemodynamics with progression of septic acute kidney injury (AKI) is limited. However, some recent data suggest that mean arterial pressure (MAP) exceeding current guidelines (60–65 mmHg) may be needed to prevent AKI. We hypothesized that higher MAP during the first 24 hours in the intensive care unit (ICU), would be associated with a lower risk of progression of AKI in patients with severe sepsis.MethodsWe identified 423 patients with severe sepsis and electronically recorded continuous hemodynamic data in the prospective observational FINNAKI study. The primary endpoint was progression of AKI within the first 5 days of ICU admission defined as new onset or worsening of AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We evaluated the association of hemodynamic variables with this endpoint. We included 53724 10-minute medians of MAP in the analysis. We analysed the ability of time-adjusted MAP to predict progression of AKI by receiver operating characteristic (ROC) analysis.ResultsOf 423 patients, 153 (36.2%) had progression of AKI. Patients with progression of AKI had significantly lower time-adjusted MAP, 74.4 mmHg [68.3-80.8], than those without progression, 78.6 mmHg [72.9-85.4], P < 0.001. A cut-off value of 73 mmHg for time-adjusted MAP best predicted the progression of AKI. Chronic kidney disease, higher lactate, higher dose of furosemide, use of dobutamine and time-adjusted MAP below 73 mmHg were independent predictors of progression of AKI.ConclusionsThe findings of this large prospective multicenter observational study suggest that hypotensive episodes (MAP under 73 mmHg) are associated with progression of AKI in critically ill patients with severe sepsis.

Acute kidney injury in patients with severe sepsis in Finnish Intensive Care Units.

Severe sepsis is one of the leading causes of acute kidney injury (AKI). Patients with sepsis‐associated AKI demonstrate high‐hospital mortality. We evaluated the incidence of severe sepsis‐associated AKI and its association with outcome in intensive care units (ICUs) in Finland.

Acute kidney injury in sepsis

Acute kidney injury (AKI) and sepsis carry consensus definitions. The simultaneous presence of both identifies septic AKI. Septic AKI is the most common AKI syndrome in ICU and accounts for approximately half of all such AKI. Its pathophysiology remains poorly understood, but animal models and lack of histological changes suggest that, at least initially, septic AKI may be a functional phenomenon with combined microvascular shunting and tubular cell stress. The diagnosis remains based on clinical assessment and measurement of urinary output and serum creatinine. However, multiple biomarkers and especially cell cycle arrest biomarkers are gaining acceptance. Prevention of septic AKI remains based on the treatment of sepsis and on early resuscitation. Such resuscitation relies on the judicious use of both fluids and vasoactive drugs. In particular, there is strong evidence that starch-containing fluids are nephrotoxic and decrease renal function and suggestive evidence that chloride-rich fluid may also adversely affect renal function. Vasoactive drugs have variable effects on renal function in septic AKI. At this time, norepinephrine is the dominant agent, but vasopressin may also have a role. Despite supportive therapies, renal function may be temporarily or completely lost. In such patients, renal replacement therapy (RRT) becomes necessary. The optimal intensity of this therapy has been established, while the timing of when to commence RRT is now a focus of investigation. If sepsis resolves, the majority of patients recover renal function. Yet, even a single episode of septic AKI is associated with increased subsequent risk of chronic kidney disease.

Population-based incidence, mortality and quality of life in critically ill patients treated with renal replacement therapy: a nationwide retrospective cohort study in finnish intensive care units

IntroductionAcute kidney injury (AKI) increases mortality and morbidity of critically ill patients. Mortality of patients treated with renal replacement therapy (RRT) is high. We aimed to evaluate the nationwide incidence of RRT-treated AKI in Finland, hospital and six-month mortality, and health-related quality of life (HRQoL) of these patients.MethodsWe performed a retrospective cohort study including all general intensive care unit (ICU) admissions in Finland in 2007 through 2008. We identified patients who had received RRT due to AKI (RRT patients) and compared these patients to ICU patients who were not treated with RRT (non-RRT patients). The HRQoL was assessed by the EQ-5D index and visual analogue scale (VAS).ResultsWe analysed the final cohort of 24,904 patients, of whom 1,686 received RRT due to AKI. The incidence of RRT-treated AKI was 6.8% (95% confidence interval (CI) 6.5 to 7.1%) among ≥ 15-year-old general ICU patients, which corresponds to a yearly population-based incidence of 19.2 per 100,000 (95% CI 17.9 to 20.5/100,000). According to RIFLE (Risk, Injury, Failure) classification 26.6% (95% CI 26.0 to 27.2%) of patients had AKI (RIFLE R-F). Hospital and six-month mortality of RRT patients were 35.0% and 49.4%. At six-months, RRT patients perceived their health as good as non-RRT patients by VAS.ConclusionsThe population-based incidence of AKI treated with RRT was 19.2 per 100,000 in Finland and 6.8% of all general ICU patients. The hospital and six-month mortality rates were lower than previously reported for ICU-treated RRT patients.

Timing of RRT Based on the Presence of Conventional Indications

BACKGROUND AND OBJECTIVES No data on the development of conventional indications for RRT (refractory acidosis, hyperkalemia, uremia, oliguria/anuria, and volume overload) related to timing of RRT exist. The prevalence of conventional indications among critically ill patients on RRT for AKI was evaluated, and patients manifesting indications versus patients without indications were compared in terms of crude and adjusted 90-day mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this substudy of the Finnish Acute Kidney Injury study conducted in 2011 and 2012 in 17 intensive care units with 2901 patients, patients were classified as pre-emptive (no conventional indications) and classic (one or more indications) RRT recipients. Patients with classic RRT were divided into classic-urgent (RRT initiated ≤ 12 hours from manifesting indications) and classic-delayed (RRT >12 hours from first indication). Additionally, 2450 patients treated without RRT were matched to patients with pre-emptive RRT. RESULTS Of 239 patients treated with RRT, 134 (56.1%; 95% confidence interval [95% CI], 49.8% to 62.4%) fulfilled at least one conventional indication before commencing RRT. Crude 90-day mortality of 134 patients with classic RRT was 48.5% (95% CI, 40.0% to 57.0%), and it was 29.5% (95% CI, 20.8% to 38.2%) for the 105 patients with pre-emptive RRT. Classic RRT was associated with a higher risk for mortality (adjusted odds ratio, 2.05; 95% CI, 1.03 to 4.09). Forty-four patients with classic-delayed RRT showed higher crude mortality (68.2%; 95% CI, 54.4% to 82.0%) compared with patients with classic-urgent RRT, and this association persisted after adjustment for known confounders (odds ratio, 3.85; 95% CI, 1.48 to 10.22). Crude 90-day mortality of 67 1:1 matched patients with pre-emptive RRT was 26.9% (95% CI, 6.3% to 37.5%), and it was 49.3% (95% CI, 37.3% to 61.2%; P=0.01) for their non-RRT matches. CONCLUSIONS Patients on RRT after one or more conventional indications had both higher crude and adjusted 90-day mortality compared with patients without conventional indications. These findings require confirmation in an adequately powered, multicenter, randomized controlled trial.

Six-month survival and quality of life of intensive care patients with acute kidney injury.

IntroductionAcute kidney injury (AKI) has high incidence among the critically ill and associates with dismal outcome. Not only the long-term survival, but also the quality of life (QOL) of patients with AKI is relevant due to substantial burden of care regarding these patients. We aimed to study the long-term outcome and QOL of patients with AKI treated in intensive care units.MethodsWe conducted a predefined six-month follow-up of adult intensive care unit (ICU) patients from the prospective, observational, multi-centre FINNAKI study. We evaluated the QOL of survivors with the EuroQol (EQ-5D) questionnaire. We included all participating sites with at least 70% rate of QOL measurements in the analysis.ResultsOf the 1,568 study patients, 635 (40.5%, 95% confidence interval (CI) 38.0-43.0%) had AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Of the 635 AKI patients, 224 (35.3%), as compared to 154/933 (16.5%) patients without AKI, died within six months. Of the 1,190 survivors, 959 (80.6%) answered the EQ-5D questionnaire at six months. The QOL (median with Interquartile range, IQR) measured with the EQ-5D index and compared to age- and sex-matched general population was: 0.676 (0.520-1.00) versus 0.826 (0.812-0.859) for AKI patients, and 0.690 (0.533-1.00) versus 0.845 (0.812-0.882) for patients without AKI (P <0.001 in both). The EQ-5D at the time of ICU admission was available for 774 (80.7%) of the six-month respondents. We detected a mean increase of 0.017 for non-AKI and of 0.024 for AKI patients in the EQ-5D index (P = 0.728). The EQ-5D visual analogue scores (median with IQR) of patients with AKI (70 (50–83)) and patients without AKI (75 (60–87)) were not different from the age- and sex-matched general population (69 (68–73) and 70 (68–77)).ConclusionsThe health-related quality of life of patients with and without AKI was already lower on ICU admission than that of the age- and sex-matched general population, and did not change significantly during critical illness. Patients with and without AKI rate their subjective health to be as good as age and sex-matched general population despite statistically significantly lower QOL indexes measured by EQ-5D.

The attributable mortality of acute kidney injury: a sequentially matched analysis*.

Objective:Acute kidney injury in the critically ill is an independent risk factor for adverse outcome. The magnitude of the impact of acute kidney injury on outcome, however, is still unclear. This study aimed to estimate the excess mortality attributable to acute kidney injury. Design:We performed a sequentially matched analysis according to the day of acute kidney injury diagnosis after ICU admission. Patients with acute kidney injury and those without acute kidney injury were matched according to age, sex, ICU admission diagnosis, Simplified Acute Physiology Score II without renal and age components, and the propensity to develop acute kidney injury at each of the four matching time points. Setting:Cohort of 16 participating ICUs from the prospective Finnish Acute Kidney Injury study. Patients:Cohort of 2,719 consecutive patients with either emergency admission or elective postsurgical patients with an expected ICU stay greater than 24 hours. Interventions:None. Measurements and Main Results:Of the 2,719 patients included in the study, acute kidney injury developed in 1,081 patients (39.8%) according to the Kidney Disease: Improving Global Outcomes—definition during ICU treatment on days 1–5. Of these, 477 patients were successfully matched to 477 patients who did not develop acute kidney injury. The 90-day mortality of the matched patients with acute kidney injury was 125 of 477 (26.2%) compared with 84 of 477 (17.6%) for their matched controls without acute kidney injury. Thus, the absolute excess 90-day mortality attributable to acute kidney injury was estimated at 8.6 percentage points (95% CI, 2.6–17.6 percentage points). The population attributable risk (95% CI) of 90-day mortality associated with acute kidney injury was 19.6% (10.3–34.1%). Conclusions:In general ICU patients, the absolute excess 90-day mortality statistically attributable to acute kidney injury is substantial (8.6%), and the population attributable risk was nearly 20%. Our findings are useful in planning suitably powered future clinical trials to prevent and treat acute kidney injury in critically ill patients.

Association of oliguria with the development of acute kidney injury in the critically ill

Urine output (UO) criterion may increase the sensitivity of the definition of acute kidney injury (AKI). We determined whether the empirically derived definition for oliguria (<0.5 ml/kg/h) is independently associated with adverse outcome. Data analysis included hourly recorded UO from the prospective, multicenter FINNAKI study conducted in 16 Finnish intensive care units. Confounder-adjusted association of oliguria of different severity and duration primarily with the development of AKI defined by creatinine criterion (Cr-AKI) or renal replacement therapy (RRT) was assessed. Secondarily, we determined the association of oliguria with 90-day mortality. Of the 1966 patients analyzed for the development of AKI, 454 (23.1%) reached this endpoint. Within this AKI cohort, 312 (68.7%) developed Cr-AKI, 21 (4.6%) commenced RRT without Cr-AKI, and 121 (26.7%) commenced RRT with Cr-AKI. Episodes of severe oliguria (<0.1 ml/kg/h) for more than 3 h were independently associated with the development of Cr-AKI or RRT. The shortest periods of consecutive oliguria independently associated with an increased risk for 90-day mortality were 6-12 h of oliguria from 0.3 to <0.5 ml/kg/h, over 6 h of oliguria from 0.1 to <0.3 ml/kg/h, and severe oliguria lasting over 3 h. Thus, our findings underlie the importance of hourly UO measurements.Kidney International advance online publication, 9 September 2015; doi:10.1038/ki.2015.269.

Association of plasma chloride values with acute kidney injury in the critically ill – a prospective observational study

Chloride‐rich fluids have been found to associate with an increased risk for acute kidney injury (AKI) among intensive care unit (ICU) patients. Studies evaluating the association of plasma chloride (Cl) with the development of AKI are few. We hypothesized that higher plasma Cl is associated with an increased risk for the development of AKI.