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Role of fluids in Acute Kidney Injury
Rachel Lennon
Consultant Paediatric Nephrologist
IV Fluids Study Day, Manchester 29th January 2016
Overview
• National Patient Safety Alert • AKI epidemiology • Pathophysiology
• Fluids and AKI
• Developments in AKI
– Diagnosis – Intervention
• Take home messages
Acute Kidney Injury
• Common global health care problem
• Increasing incidence
• 20% hospital admissions
• $10 billion in the USA per year
• Increased hospital stay
• Increased morbidity and mortality
• No specific therapy
• Think Kidneys Campaign
• AKI Algorithm
• Electronic AKI alerts
• Patient Safety Alert
• 9th March 2015
National AKI algorithm
• NHS England
• Standardising the early identification of AKI
• AKI 1,2,3
• Paediatrics included
– scale of problem?
Serum creatinine
result exists?
Previous result
Within 0 – 365 days?
Index creatinine value
Defined as
C1
If Result within
0 – 7 days
Then:
If Result within
8 – 365 days
Then:
Find lowest
value
Define as
RV1
Calculate RV ratio
C1 / RV1
Find MEDIAN
of results
Define as
RV2
Calculate RV ratio
C1 / RV2
Is higher RV ratio
≥ 3.0?
Is higher RV ratio
≥ 2.0 and < 3.0?
Is higher RV ratio
≥ 1.5 and < 2.0?
ALERT!
?AKI 3
Alert!
?AKI 2
ALERT!
?AKI 1
Is higher RV ratio
≥ 1.5?
Has change occurred
Within 48hrs?
Is D > 26 umol/L?Report without
alert
Report without alert.
Send to authorisation Q
If creatinine has
Increased > 26 umol/L
In < 7 days.
Consider requesting
repeat If CKD
unlikely.
< RI? Flag low
Within RI? No flag
Flag High
?AKI ?CKD
Suggest
RepeatAlgorithm for detecting Acute
Kidney Injury (AKI) based on
serum creatinine changes with
time
This algorithm relates to the
NHS England patient safety
alert: NHS/PSA/D/2014/010
RI =Population
Reference Interval
(Age and sex
related if available)
RV = Reference value. Defined as:
the creatinine value with which an index
creatinine value is compared
D = difference between
current and lowest
previous result within
48hrs
YES
NO YES
YES
NO
NO
NO YES
YES
YES
YES
YES
NO
NO
NO
NO
ULRI = upper
limit of
reference
interval
Is age < 18 years?Serum creatinine
> x3 ULRI?
Serum creatinine
> 354 umol/L?
YES
YES
YES
YES
NO
NO
NO
www.england.nhs.uk
Is AKI an issue in paediatrics?
• Depends on AKI definition used in studies
• 9-fold increase since between 1980-2005 – Vachvanichsanong P, Pediatrics 2006
• PICU:
– 25% all admissions
– 82% AKI in critically ill children (ventilation, inotropes)
– 49% AKI Royal Manchester Children’s Hospital • McCaffrey J et al, Pediatric Nephrology 2015
Paediatric AKI in England 2015
• 6 month study
• 3x tertiary and 3x DGH centres
• 57,278 creatinine values
• 5325 alerts, n=1112 patients
• 66 notes reviewed
• 18% recognised AKI
62% 16%
22%
% AKI Stage
AKI 1
AKI 2
AKI 3
Aetiology
Goldstein S, Blood Purification 2012
80’s-90’s:Primary renal (eg: HUS), sepsis, burns Shift: Secondary to systemic disease or treatment
Overview
National Patient Safety Alert AKI epidemiology • Pathophysiology
• Fluids and AKI
• Developments in AKI
– Diagnosis – Intervention
• Take home messages
Overview
National Patient Safety Alert AKI epidemiology Pathophysiology
• Fluids and AKI
• Developments
– Diagnosis – Intervention
• Take home messages
Can fluids cause AKI?
• 0.9% saline most common resuscitation fluid
• Associated with AKI and increased mortality
• High chloride contributes to AKI – Hyperchloremia and metabolic acidosis – Renal vasoconstriction – Decreased glomerular GFR
• Buffered/balanced fluids less AKI • Evidence for increased AKI with colloids in sepsis
Fluid management in AKI Concepts:
1. AKI in sepsis results from reduced renal blood flow
2. Fluid resuscitation restores renal perfusion
Legrand • Haemorhagic model
• Rats bled to MAP 30mmHg resuscitated with
normal or hypertonic saline
• Crystalloid did not improve renal microvascular perfusion
• Established AKI not responsive to more fluids
Bellamo • Hyperdynamic animals have
increased renal blood flow
• Kidneys are perfused • BUT glomerular filtration
decreased
• Downstream consequences
2014
Removal Timing and rates Intermittent HD vs CVVH
Maintenance Needs (blood products/medications/nutrition) versus Excretion of volume and solutes
Resuscitation/repletion Restore end-organ perfusion Early goal directed therapy (physiological parameters)
Three phases of fluid management…
Transition between phases unclear…
• 263 Emergency Department patients
• Randomised to 6 hours-goal-directed (CVP/MAP/O2/Hct) or standard fluid therapy
• Reduced mortality (30.5% vs 46.5%) with EGDT
• AKI not assessed
• Issues with patient exclusion and sample size • Paediatric data also support EGDT for improved survival
• 1243 adult patients with AKI Pittsburgh • Protocol versus usual care • AKI: 37.6% vs 38.1% usual care AKI • No difference in AKI duration and RRT rates • No difference in complete and partial recovery from AKI • Fluid overload 8.3% vs 6.3% fluid
• Long term F/U? • AKI common but not influenced by protocol
• Cluster randomised double crossover trail (adults/ICU/New Zealand) • 2278 patients receiving IV fluids • Randomised to 0.9% or buffered crystalloid (PL-148) • Primary outcome 2-fold increase in SCr • Secondary outcome RRT/in-hospital mortality • AKI: 9.6% vs 9.2% in saline group • RRT 3.3% vs 3.4% • Death 7.6 vs 8.6% • Effect in higher risk groups not excluded
Overview
National Patient Safety Alert AKI epidemiology Pathophysiology
Fluids and AKI
• Developments
– Diagnosis – Intervention
• Take home messages
Interventions
• No therapeutic agent for ‘AKI’
– Many failed medicine trials
– Animal models eg: IGF1- too late
– Test drugs with a wider therapeutic window
• Prevention and treatment studies
• Improve current practice
Symons, J Pediatr Nephrol 2013
Future possibilities: Optimisation of volume status Inhibition of apoptosis Adenosine receptor antagonism Immune modulation Ischaemic preconditioning Therapeutic hypothermia Stem cell therapy
AKI trials- registered 2011
• 126 clinical trials – 118 adults, 8 in children – 65% prevention trials (timed insult)
• Many inadequately powered – need 800 per study arm
• Few use agreed criteria
• 21/22 treatment trials – based on ICU and RRT
Faubel, S CJASN 2012
RRT- Trials
• Improve current practice:
• Eg: Improved methods of anticoagulation
– Loss of circuits
• Eg: Early initiation
– Fluid overload
Other interventions
• Detection – Patient alerts
• Prevention of secondary injury
• Medicine dosing to prevent renal injury – What is the correct dose? – Nephrotoxicity/adequate treatment
• Early nephrology consult – Non-ICU based patients – Evidence it helps!
Take home messages
• AKI is a common problem
• Respond to Safety Alerts
• Fluids – A potential cause of AKI – Type, amount, removal
• New biomarkers
• Outcome – High risk of chronic kidney disease
Acknowledgements
Rachael Barber Paediatric Intensivist Beatrice Coupes Clinical Scientist Chris Chaloner Consultant Biochemist Philip Hudnott PICU Research Nurse James McCaffrey MRC clinical fellow Stephen Playfor Paediatric Intensivist Adam Sutherland Senior Clinical Pharmacist Nick Webb Paediatric Nephrologist