crrt: what are (some of) the unsolved issues...feature elain akiki ideal-icu starrt-aki country...

RRT: What Are (Some of) the Unsolved IssuesSean M Bagshaw, MD, MSc

Department of Critical Care Medicine, University of Alberta, Edmonton,

Canada

37th Vicenza Course on AKI & CRRT

Vicenza, Italy

Wednesday, May 29, 2019 ~ 10:00 – 10:20

2019 Disclosures

•Salary: Canada/Alberta government

•Grant: Canada/Alberta government, Baxter

•Consulting: Baxter, CNA Diagnostics, Spectral Medical

•Data Safety Monitoring: CytoPherx

•Co-PI: STARRT-AKI trial

Unsolved Issue # 1: KDIGO Severity Staging To Start RRT

KDIGO CPG for AKI_KI (suppl) 2012

KDIGO AKI Staging As Thresholds for Starting RRT

In patients with AKI RIFLE-F ~ 14% treated with RRT (only 1% with AKI RIFLE-I)1

In patients with AKI KDIGO Stage 3 ~ 66% received RRT (n=272/410; 9% overall)2

In patients with AKI KDIGO Stage 3 ~ 45% received RRT (n=243/540; 13.5% overall)3

1. Hoste E et al Crit Care 2006; 2. Nisula S et al ICM 2013; 3. Hoste E et al ICM 2015

Feature ELAIN AKIKI IDEAL-ICU STARRT-AKI

Country Germany France France Multiple (15+)

No. of Sites 1 31 29 >135

Participants 231 620 488 3,000*

Case-mix Mostly surgical Mostly medical Septic Mixed

Sample calculation (ARR) 18% 15% 10% 6%

Clinician Equipoise No No No Yes

Interventions:

EARLY KDIGO stage 2 KDIGO stage 3 KDIGO stage 3 KDIGO stage 2

DELAYED KDIGO stage 3 Specific criteria* 48 hours Specific criteria*

Primary Endpoint 90-day mortality 60-day mortality 90-day mortality 90-day mortality

DELAYED Death Rate 54.7% 49.7% 54% 37.0%*

Iwashyna et al AJRCCM 2017

Prowle et al KI 2015

Gaudry et al NEJM 2016

•HYPOTHESIS: A strategy of delayed RRT initiation would confer greater survival benefit when compared to a strategy of early RRT initiation among critically ill patients with severe AKI (KDIGO stage 3)

Gaudry et al NEJM 2016

•Death modified by acuity + RRT:•Early: 48.5%•Delayed – NO RRT: 37.1%•Delayed – RRT: 61.8%

Unsolved Issue # 2: Kidney Biomarkers for Starting RRT

Klein SJ et al ICM 2018

ELAIN Trial (n=231) applied plasma NGAL >150 ng/mL as “inclusion” criteria

Plasma NGAL >150 ng/mL as “inclusion” criteria

604 patients screened; only 3 patients excluded for pNGAL <150 ng/mL

Zarbock et al ELAIN JAMA 2016

STARRT-AKI (Pilot) Trial (n=101) applied blood NGAL >400 ng/mL for “inclusion”

While Blood NGAL ≥400 ng/mL as “inclusion” criteria

Median >1,300 ng/mL (lower quartile 774)

Wald et al KI 2015

Prevention of CSA-AKI by Implementing the “KDIGO” Bundle (n=276) applied urine NephroCheck®

Patients undergoing cardiac surgery with [TIMP-2*IGFBP-7] ≥0.3 at 4 hours post-operatively

Application of [TIMP-2*IGFBP-7] provided “predictive enrichment” for risk of AKI

882 screened – 495 (56%) excluded

↑ incidence of post-op AKI

Zarbock et al PrevAKI ICM 2017

Pilot trial of Early vs. Delayed RRT allocated by baseline plasma NGAL (n=40)

Single centre pilot trial of when to start RRT in AKI (Stage 2)

Threshold pNGAL >400 ng/mL to randomize

RRT received by 100% in Early and 40% in Delayed

Srisawat et al J Crit Care 2017

Unsolved Issue # 3: FST For Starting RRT

Chawla LS et al Crit Care 2014

Furosemide Stress Test for Predicting KDIGO AKI Stage 3

FST: furosemide 1-1.5 mg/kg IV bolus

Urine output ≥ 200 mL in 2 hours

Chawla LS et al Crit Care 2014

Furosemide Stress Test for Predicting KDIGO AKI Stage 3

Sensitivity: 87%

Specificity: 84%

AUC: 0.87Chawla LS et al Crit Care 2014

Furosemide Stress Test for KDIGO AKI Stage 3

Rewa O et al J Crit Care 2019

Largely confirmed in prospective observational cohort study

RRT (11%); Sensitivity 70%; Specificity 77%

Furosemide Stress Test as Decision Support for Starting RRT

Lumlertgul et al Crit Care 2018

Furosemide Stress Test To Triage for A Trial of When to Start RRT

Eligible patients received furosemide stress test

FST responsive patients (n=44; 27%) excluded

Fewer FST responsive patients received RRT (n=6; 14%)

Lumlertgul et al Crit Care 2018

Furosemide Stress Test To Triage for A Trial of When to Start RRT

Patients allocated to “standard” RRT ~ 75% received RRT

No difference in mortality (62% vs. 58%) or any other secondary endpoints

Lumlertgul et al Crit Care 2018

Unsolved Issue # 4: Quality of Care in RRT

ADQI 22 - Kashani et al CJASN 2019

ADQI 22 - Kashani et al CJASN 2019

What aspects of your CRRT care do you measure?

Quality CRRT Care

•What is your average filter lifespan?

•What is your average treatment downtime?

•What is your average time to restart after treatment interruption?

•What is your average delivered dose per day?

•What is your average fluid removal per day?

Clark WR et al. Int J Artif Organs 2016

•Seldom routine monitoring/reporting of quality indicators for CRRT

•Paucity of evidence-informed performance standards for CRRT

ADQI 22 - Kashani et al CJASN 2019

MACHINE

CIS

CRRT Quality ManagementDATA INFORMATION

StructureProcess

Outcome

CDSCQI

Performance(Benchmarks)

KNOWLEDGE

Striving for Quality CRRT Care

•Implement and evaluate the feasibility of these QIs into your clinical practice ~ understand your data

•Evaluate the association of these QIs with care processes and patient and health system-related outcomes ~ understand your culture

•Evaluate performance, generate CRRT quality reports ~ generate your own benchmarks

Thank You For Your Attention!

bagshaw@ualberta.ca

@drseanbagshaw