Critical Care Bulletin: July 2025

 

Association of hospital-level continuous kidney replacement therapy use and mortality in critically ill patients with acute kidney injury

Intensive Care Medicine, Published: 30 June 2025

Purpose

In numerous high-risk medical and surgical conditions, an increased volume of patients and procedures is associated with improved processes and survival. This study examined the association of hospital-level continuous kidney replacement therapy (CKRT) utilization rates with all-cause hospital mortality in critically ill patients with acute kidney injury (AKI).

Methods

This multicenter cohort study used data from patients admitted to the intensive care unit (ICU) within the Premier Incorporated AI (PINC-AI) database. Patients were critically ill adults with AKI receiving kidney replacement therapy (KRT) in U.S. hospitals that offered both CKRT and intermittent hemodialysis. Hospitals were characterized according to their CKRT utilization in the ICU, and risk-adjusted association with all-cause hospital mortality by day 90 was estimated.

Results

Among 49,685 patients with AKI admitted to 426 acute care U.S. hospitals and treated with KRT in the ICU, a higher hospital-level CKRT utilization rate was associated with lower patient-level risk-adjusted hospital mortality. Hospitals with higher CKRT utilization rates (CKRT use in ≥ 31.5% of KRT patients per year) had a 15% lower adjusted probability of death compared with hospitals with lower CKRT utilization rates (CKRT use in < 8% of KRT patients per year). When compared with the first quartile of hospital-level CKRT use, the third (adjusted hazard ratio [aHR], 0.93, 95%CI: 0.89–0.98) and fourth (aHR, 0.85, 95%CI: 0.81–0.89) quartiles were associated with lower risk-adjusted hospital mortality. Findings were consistent in several sensitivity analyses.

Conclusions

Among critically ill adults with AKI requiring KRT, treatment in hospitals with higher CKRT utilization rates was associated with reduced hospital mortality.

 

Sex Differences in Treatment of Adult Intensive Care Patients: A Systematic Review and Meta-Analysis

 

by Modra, Lucy J.; Higgins, Alisa M.; Abeygunawardana, Vihangi S.; Vithanage, Ruvini N.; Bailey, Michael J.; Bellomo, Rinaldo 

 

Critical Care Medicine: June 2022 - Volume 50 - Issue 6 - p 913-923

 

OBJECTIVES: 

To evaluate and synthesize the available literature on sex differences in the treatment of adult ICU patients.

DATA SOURCES: 

MEDLINE and EMBASE.

STUDY SELECTION: 

Two reviewers independently screened publications to identify observational studies of adult ICU patients that explicitly examined the association between sex and ICU treatment—specifically, mechanical ventilation, renal replacement therapy, and length of stay.

DATA EXTRACTION: 

We extracted data independently and in duplicate: mean age, illness severity, use of mechanical ventilation and renal replacement therapy, and length of stay in ICU and hospital. We assessed risk of bias using the Newcastle-Ottawa Scale. We used a DerSimonian-Laird random-effects model to calculate pooled odds ratios (ORs) and mean differences between women and men.

DATA SYNTHESIS: 

We screened 4,098 publications, identifying 21 eligible studies with 545,538 participants (42.7% women). The study populations ranged from 246 to 261,255 participants (median 4,420). Most studies (76.2%) were at high risk of bias in at least one domain, most commonly representativeness or comparability. Women were less likely than men to receive invasive mechanical ventilation (OR, 0.83; 95% CI, 0.77–0.89; I2 = 90.4%) or renal replacement therapy (OR, 0.79; 95% CI, 0.70–0.90; I2 = 76.2%). ICU length of stay was shorter in women than men (mean difference, –0.24 d; 95% CI, –0.37 to –0.12; I2 = 89.9%). These findings persisted in meta-analysis of data adjusted for illness severity and other confounders and also in sensitivity analysis excluding studies at high risk of bias. There was no significant sex difference in duration of mechanical ventilation or hospital length of stay.

CONCLUSIONS: 

Women were less likely than men to receive mechanical ventilation or renal replacement therapy and had shorter ICU length of stay than men. There is substantial heterogeneity and risk of bias in the literature; however, these findings persisted in sensitivity analyses.

 

Accelerated versus standard initiation of renal replacement therapy for critically ill patients with acute kidney injury: a systematic review and meta-analysis of RCT studies

 

Accelerated versus standard initiation of renal replacement therapy for critically ill patients with acute kidney injury: a systematic review and meta-analysis of RCT studies

 

by Heng-Chih Pan, Ying-Ying Chen, I-Jung Tsai, Chih-Chung Shiao, Tao-Min Huang, Chieh-Kai Chan, Hung-Wei Liao, Tai-Shuan Lai, Yvonne Chueh, Vin-Cent Wu and Yung-Ming Chen 

 

Critical Care volume 25, Article number: 5 (2021)

 

Background

Acute kidney injury (AKI) is a common yet possibly fatal complication among critically ill patients in intensive care units (ICU). Although renal replacement therapy (RRT) is an important supportive management for severe AKI patients, the optimal timing of RRT initiation for these patients is still unclear.

Methods

In this systematic review, we searched all relevant randomized controlled trials (RCTs) that directly compared accelerated with standard initiation of RRT from PUBMED, MEDLINE, EMBASE, and Cnki.net published prior to July, 20, 2020. We extracted study characteristics and outcomes of being free of dialysis, dialysis dependence and mortality. We rated the certainty of evidence according to Cochrane methods and the GRADE approach.

Results

We identified 56 published relevant studies from 1071 screened abstracts. Ten RCTs with 4753 critically ill AKI patients in intensive care unit (ICU) were included in this meta-analysis. In our study, accelerated and standard RRT group were not associated with all-cause mortality (log odds-ratio [OR]: − 0.04, 95% confidence intervals [CI] − 0.16 to 0.07, p = 0.46) and free of dialysis (log OR: − 0.03, 95% CI − 0.14 to 0.09, p = 0.65). In the subgroup analyses, accelerated RRT group was significantly associated with lower risk of all-cause mortality in the surgical ICU and for those who received continuous renal replacement therapy (CRRT). In addition, patients in these two subgroups had higher chances of being eventually dialysis-free. However, accelerated initiation of RRT augmented the risk of dialysis dependence in the subgroups of patients treated with non-CRRT modality and whose Sequential Organ Failure Assessment (SOFA) score were more than 11.

Conclusions

In this meta-analysis, critically ill patients with severe AKI would benefit from accelerated RRT initiation regarding all-cause mortality and being eventually free of dialysis only if they were surgical ICU patients or if they underwent CRRT treatment. However, the risk of dialysis dependence was increased in the accelerated RRT group when those patients used non-CRRT modality or had high SOFA scores. All the literatures reviewed in this study were highly heterogeneous and potentially subject to biases.

Continuous Renal Replacement Therapy in Pediatric Severe Sepsis: A Propensity Score-Matched Prospective Multicenter Cohort Study in the PICU

Continuous Renal Replacement Therapy in Pediatric Severe Sepsis: A Propensity Score-Matched Prospective Multicenter Cohort Study in the PICU

by Miao, Huijie; Shi, Jingyi; Wang, Chunxia; Lu, Guoping; Zhu, Xiaodong; Wang, Ying; Cui, Yun; Zhang, Yucai 

Critical Care Medicine: October 2019 - Volume 47 - Issue 10 - p e806-e813

Objectives: Continuous renal replacement therapy becomes available utilization for pediatric critically ill, but the impact of mortality rate in severe sepsis remains no consistent conclusion. The aim of the study is to assess the effect of continuous renal replacement therapy in pediatric patients with severe sepsis and the impact this therapy may have on their mortality.

Design: Propensity score-matched cohort study analyzing data prospectively collected by the PICUs over 2 years (2016–2018).

Setting: Four PICUs of tertiary university children’s hospital in China. Patients: The consecutive patients with severe sepsis admitted to study PICUs were enrolled from July 2016 to June 2018. Interventions: The patients were divided into the continuous renal replacement therapy group and the conventional (noncontinuous renal replacement therapy) group.

Measurements and Main Results: A total of 324 patients with severe sepsis were enrolled. The hospital mortality rate was 35.6% (64/180) in the continuous renal replacement therapy group and 47.9% (69/144) in the noncontinuous renal replacement therapy group. After propensity score adjustment, the hospital mortality rate was 21.3% (29/136) in the continuous renal replacement therapy group and 32.4% (44/136) in the noncontinuous renal replacement therapy group. In subgroup analysis, the relative risk of dying was 0.447 (95% CI, 0.208–0.961) only in patients complicated by acute respiratory distress syndrome (p = 0.037), but not in patients with shock, acute kidney injury, acute liver dysfunction, encephalopathy, and fluid overload greater than 10%. The mean duration of continuous renal replacement therapy was 45 hours (26–83 hr) with an ultrafiltration rate of 50 mL/kg/hr. The level of interleukin-6 was decreased, and the percent of natural killer cells (%) was improved in the continuous renal replacement therapy group compared with the noncontinuous renal replacement therapy group. Furthermore, continuous renal replacement therapy was an independently significant risk factor for hospital mortality in pediatric patients with severe sepsis, and the interval between continuous renal replacement therapy initiation and PICU admission was an independent risk factor for hospital mortality in patients receiving continuous renal replacement therapy.

Conclusions: Continuous renal replacement therapy with an ultrafiltration rate of 50 mL/kg/hr decreases hospital mortality rate in pediatric severe sepsis, especially in patients with acute respiratory distress syndrome.

Renin as a Marker of Tissue-Perfusion and Prognosis in Critically Ill Patients*

Renin as a Marker of Tissue-Perfusion and Prognosis in Critically Ill Patients*

by Gleeson, Patrick J.; Crippa, Ilaria Alice; Mongkolpun, Wasineenart; Cavicchi, Federica Zama; Van Meerhaeghe, Tess; Brimioulle, Serge; Taccone, Fabio Silvio; Vincent, Jean-Louis; Creteur, Jacques

Critical Care Medicine: February 2019 - Volume 47 - Issue 2 - p 152–158

Objectives: To characterize renin in critically ill patients. Renin is fundamental to circulatory homeostasis and could be a useful marker of tissue-perfusion. However, diurnal variation, continuous renal replacement therapy and drug-interference could confound its use in critical care practice.

Design: Prospective observational study. Setting: Single-center, mixed medical-surgical ICU in Europe. Patients: Patients over 18 years old with a baseline estimated glomerular filtration rate greater than 30 mL/min/1.73 m2 and anticipated ICU stay greater than 24 hours. Informed consent was obtained from the patient or next-of-kin. Interventions: Direct plasma renin was measured in samples drawn 6-hourly from arterial catheters in recumbent patients and from extracorporeal continuous renal replacement therapy circuits. Physiologic variables and use of drugs that act on the renin-angiotensin-aldosterone system were recorded prospectively. Routine lactate measurements were used for comparison.

Measurements and Main Results: One-hundred twelve arterial samples (n = 112) were drawn from 20 patients (65% male; mean ± SD, 60 ± 14 yr old) with septic shock (30%), hemorrhagic shock (15%), cardiogenic shock (20%), or no circulatory shock (35%). The ICU mortality rate was 30%. Renin correlated significantly with urine output (repeated-measures correlation coefficient = –0.29; p = 0.015) and mean arterial blood pressure (repeated-measures correlation coefficient = –0.35; p < 0.001). There was no diurnal variation of renin or significant interaction of renin-angiotensin-aldosterone system drugs with renin in this population. Continuous renal replacement therapy renin removal was negligible (mass clearance ± SD 4% ± 4.3%). There was a significant difference in the rate of change of renin over time between survivors and nonsurvivors (–32 ± 26 μU/timepoint vs +92 ± 57 μU/timepoint p = 0.03; mean ± SEM), but not for lactate (–0.14 ± 0.04 mM/timepoint vs +0.15 ± 0.21 mM/timepoint; p = 0.07). Maximum renin achieved significant prognostic value for ICU mortality (receiver operator curve area under the curve 0.80; p = 0.04), whereas maximum lactate did not (receiver operator curve area under the curve, 0.70; p = 0.17).

Conclusions: In an heterogeneous ICU population, renin measurement was not significantly affected by diurnal variation, continuous renal replacement therapy, or drugs. Renin served as a marker of tissue-perfusion and outperformed lactate as a predictor of ICU mortality.

Deresuscitation of Patients With Iatrogenic Fluid Overload Is Associated With Reduced Mortality in Critical Illness*

Deresuscitation of Patients With Iatrogenic Fluid Overload Is Associated With Reduced Mortality in Critical Illness*

by Silversides, Jonathan A.; Fitzgerald, Emma; Manickavasagam, Uma S.; Lapinsky, Stephen E.; Nisenbaum, Rosane; Hemmings, Noel; Nutt, Christopher; Trinder, T. John; Pogson, David G.; Fan, Eddy; Ferguson, Andrew J.; McAuley, Daniel F.; Marshall, John C.; for the Role of Active Deresuscitation After Resuscitation (RADAR) Investigators  

Critical Care Medicine: October 2018 - Volume 46 - Issue 10 - p 1600–1607

Objectives: To characterize current practice in fluid administration and deresuscitation (removal of fluid using diuretics or renal replacement therapy), the relationship between fluid balance, deresuscitative measures, and outcomes and to identify risk factors for positive fluid balance in critical illness.

Design: Retrospective cohort study. Setting: Ten ICUs in the United Kingdom and Canada. Patients: Adults receiving invasive mechanical ventilation for a minimum of 24 hours. Interventions: None. Measurements and Main Results: Four-hundred patients were included. Positive cumulative fluid balance (fluid input greater than output) occurred in 87.3%: the largest contributions to fluid input were from medications and maintenance fluids rather than resuscitative IV fluids. In a multivariate logistic regression model, fluid balance on day 3 was an independent risk factor for 30-day mortality (odds ratio 1.26/L [95% CI, 1.07–1.46]), whereas negative fluid balance achieved in the context of deresuscitative measures was associated with lower mortality. Independent predictors of greater fluid balance included treatment in a Canadian site.

Conclusions: Fluid balance is a practice-dependent and potentially modifiable risk factor for adverse outcomes in critical illness. Negative fluid balance achieved with deresuscitation on day 3 of ICU stay is associated with improved patient outcomes. Minimization of day 3 fluid balance by limiting maintenance fluid intake and drug diluents, and using deresuscitative measures, represents a potentially beneficial therapeutic strategy which merits investigation in randomized trials.

Safety and Efficacy of Combined Extracorporeal CO2 Removal and Renal Replacement Therapy in Patients With Acute Respiratory Distress Syndrome and Acute Kidney Injury: The Pulmonary and Renal Support in Acute Respiratory Distress Syndrome Study

Safetyand Efficacy of Combined Extracorporeal CO2 Removal and Renal Replacement Therapy in Patients With Acute Respiratory Distress Syndrome and Acute Kidney Injury: The Pulmonary and Renal Support in Acute Respiratory Distress Syndrome Study
Allardet-Servent, J et al.
Critical Care Medicine: December 2015 - Volume 43 - Issue 12 - p 2570–2581


Objective: To assess the safety and efficacy of combining extracorporeal CO2 removal with continuous renal replacement therapy in patients presenting with acute respiratory distress syndrome and acute kidney injury. Design: Prospective human observational study.
Settings: Patients received volume-controlled mechanical ventilation according to the acute respiratory distress syndrome net protocol. Continuous venovenous hemofiltration therapy was titrated to maintain maximum blood flow and an effluent flow of 45 mL/kg/h with 33% predilution.
Patients: Eleven patients presenting with both acute respiratory distress syndrome and acute kidney injury required renal replacement therapy. Interventions: A membrane oxygenator (0.65 m2) was inserted within the hemofiltration circuit, either upstream (n = 7) or downstream (n = 5) of the hemofilter. Baseline corresponded to tidal volume 6 mL/kg of predicted body weight without extracorporeal CO2 removal. The primary endpoint was 20% reduction in PaCO2 at 20 minutes after extracorporeal CO2 removal initiation. Tidal volume was subsequently reduced to 4 mL/kg for the remaining 72 hours. Measurements and Main Results: Twelve combined therapies were conducted in the 11 patients. Age was 70 ± 9 years, Simplified Acute Physiology Score II was 69 ± 13, Sequential Organ Failure Assessment score was 14 ± 4, lung injury score was 3 ± 0.5, and PaO2/FIO2 was 135 ± 41. Adding extracorporeal CO2 removal at tidal volume 6 mL/kg decreased PaCO2 by 21% (95% CI, 17–25%), from 47 ± 11 to 37 ± 8 Torr (p < 0.001). Lowering tidal volume to 4 mL/kg reduced minute ventilation from 7.8 ± 1.5 to 5.2 ± 1.1 L/min and plateau pressure from 25 ± 4 to 21 ± 3 cm H2O and raised PaCO2 from 37 ± 8 to 48 ± 10 Torr (all p < 0.001). On an average of both positions, the oxygenator’s blood flow was 410 ± 30 mL/min and the CO2 removal rate was 83 ± 20 mL/min. The oxygenator blood flow (p <0 .001="" and="" br="" co2="" concern.="" hemofilter.="" higher="" membrane="" no="" of="" oxygenator="" p="0.083)" placed="" rate="" removal="" safety="" the="" there="" upstream="" was="" were="" when="">Conclusions: Combining extracorporeal CO2 removal and continuous venovenous hemofiltration in patients with acute respiratory distress syndrome and acute kidney injury is safe and allows efficient blood purification together with enhanced lung protective ventilation.

Argatroban v Lepirudin in critically ill patients

Argatroban versus Lepirudin in critically ill patients: A randomized controlled trial. Critical Care, Oct. 2014, 18:588

Treschan, T.A., et al.

http://ccforum.com/content/pdf/s13054-014-0588-8.pdf

Critically ill patients often require renal replacement therapy accompanied by thrombocytopenia. Thrombocytopenia during heparin anticoagulation may be due to heparin-induced thrombocytopenia with need for alternative anticoagulation. Therefore, we compared argatroban and lepirudin in critically ill surgical patients. Following institutional review board approval and written informed consent, critically ill surgical patients more than or equal to 18 years with suspected heparin-induced thrombocytopenia, were randomly assigned to receive double-blind argatroban or lepirudin anticoagulation targeting an activated Partial Thromboplastin Time (aPTT) of 1.5 to 2 times baseline. In patients requiring continuous renal replacement therapy we compared the life-time of hemodialysis filters. We evaluated in all patients the incidence of bleeding and thrombembolic events. Conclusions: This first randomized controlled double-blind trial comparing two direct thrombin inhibitors showed comparable effectiveness for renal replacement therapy, but suggests fewer bleeds in surgical patients with argatroban anticoagulation.