AKI & Traumae Kidney after major trauma major after injury Kidney The Royal London Hospital, John RProwle Consultant Consultant in Intensive Care and Renal Medicine Queen Queen Mary University of London Senior Lecturer Clinical MA MSc MA MSc MD FRCPFFICM

Barts

Health Health NHS Trust

AKI & Traumae AKI & Traumae Acute Kidney Injury?

AKI & Traumae • • • • 9449illtrauma criticallypatients AKI mortality risk of as independent Mortality AKI 18.1 – – – – – – Failure Failure Injury Risk co female Older, - morbidities

%

16.7% v 7.8% 16.7% v

OR OR 1.88 OR OR 2.7 OR 1.6 2.29 1.68

AKI & Traumae Hammersmith Hospital (1910 Prof. Eric 1940 London - 2003) Bywaters –

1941

AKI & Traumae Bywaters • • • • • albumin and dark dark and albumin contains urine The appear soon damage renal Signs of falls pressure His blood limb of the swelling from apart good he looks …. On admission hours several for buried been had casts granular brown

and Beale

AKI & Traumae AKI & Traumae included in the Patients included admitted in the ICUin the admitted Traumaticpatients Traumaticpatients visited inthe visited AE (N=7128) (N=858) (N=871) study

patients 9 Survival lessthan24hours: 4 patients ≥ 300µmol/L:Creatinine by Excluded

AKI & Traumae Male (%) Age Characteristics Patient Mortality (day) stay of length Hospital (day) stayICU of length APACHE II NISS

34 34 (22 41 (27 5.5 5.5 (3 Non Non AKI 17 17 (7 11 (8 (n=722) 11.8% 80.9 - - - - - 16) 37) 12) 50) 56)

16 16 (12 34 (22 49 (33 21 21 (8 8 8 (3 Stage I Stage (n=79) 20.3% AKI 83.5 - - 15) - - - 42) 19) 50) 66)

16 16 (13 41 (25 63 (45 20 20 (6 Stage II Stage (n=13) 5 5 (4 23.1% AKI 84.6 - - - - - 32) 8) 17) 57) 78)

47.5 47.5 (27 15.5 15.5 (6.5 17 17 (13 8.5 8.5 (5.0 34 34 (25 Stage III Stage (n=44) 38.6% AKI 84.1 - 26.5) - - - 50) 64.5)

- 23) 50)

P value <0.001 <0.001 <0.001 <0.001 0.630 0.192 0.420

AKI & Traumae AKI & Traumae NISS NISS score APACHEII AKI Stage Non vs III AKI Stage Non vs II AKI Stage Non vs I Predictors

- - - (4.37 (1.99 (1.21 Crude OR 5.78* 5.78* 3.30* 1.56* - - -

5.48) 2.00) 7.64) ICU

mortality Adjusted OR Adjusted (1.04 (1.15 (2.10 (0.63 (0.64

1.06* 1.19* 4.56* 2.42 2.42 1.28 - - - - - 1.07) 1.23) 9.92) 9.35) 2.54)

Primary Outcome

(2.86 (0.75 (1.17 Crude OR 5.41* 5.41* 1.95* 2.24 2.24 -

- -

Hospital Hospital 10.22)

6.65) 3.27)

mortality Adjusted OR Adjusted (1.15 (1.04 (1.60 (0.49 (0.91

1.18* 1.05* 3.43* 1.85 1.69 - - - - - 1.22) 1.06) 7.34) 7.00) 3.14)

AKI & Traumae Predicting Predicting AKI at admission • • • • Admission: Score Severity New Injury Sex Age – – – – – – Bloodtransfusion BloodPressure Creatine Phosphate Lactate Creatinine

Kinease

AKI & Traumae Predicting Predicting AKI 2 - 3

AKI & Traumae RRT

AKI & Traumae or AKI - 2

AKI & Traumae What causes AKIafter trauma? • • • • • • • • Syndrome AbdominalCompartment Drugs Massive Transfusion Tract Direct Traumato the Renal Hypovolaemic – – – – Contrast Iliac Tissue Injury

Embolisation

AKI & Traumae of AKI cause important most the into Sepsis: a digression

AKI & Traumae ANNALS SURGERY OF 22(1)

·

MARCH 2014MARCH

AKI & Traumae AKI & Traumae Pathophysiology Pathophysiology of Rhabdomyolysis • muscle’ Rhabdomyolysis – – – Release Release of muscle cell contents Depletion of ATPwithin the Direct • • • • • • Converselyfluidto losscompartmentsmuscle Myoglobin Destruction of UnregulatedCa intracellular Ischaemia reperfusionand Trauma – –

sarcolemmic Secondary compartment syndromes Hypovolaemia

myofibrillar –

‘the dissolution of striped(skeletal) ‘the dissolution injury

, cytoskeletalandmembrane proteins , myocyte 2+

increase

AKI & Traumae Myoglobin Myoglobin and AKI • Myoglobin – – – – – – – rhabdomyolysis Myoglobinuria Urine becomes red when concentration is >100mg/ Appears in urine when concentration is >0.5 Tubular cells epithelial metabolise it Freely filtered at the glomerulus 17.8 Iron and O kDa

2

binding binding protein only occurs only occurs in the context of

- 1.5mg/ dL dL

AKI & Traumae Myoglobin Myoglobin and AKI • The toxic effects of myoglobin – – – – Hypovolaemia Tubular obstruction Direct Intra • • • • • • peroxidation. states that generatesradicalspeciesthatinduce lipid consequenceof from cellscause can severeoxidative asadamage Haemoproteins Catalyticfree iron Haem TNFα Endothelin Tx renal renal

A2 and

vasoconstriction tubular injury

1

, haem haemoglobin

redoxcyclingferric andbetween

andmyoglobin, oncereleased …

ferryl

AKI & Traumae and AKI Biochemical Markers ofMuscleinjury de Brancaccio et al • • Meijer 2003 al et ICM Serum Creatine Creatine Serum Creatinine Serum – – – – AKI* correlates to development of Peak CK and admission CK damage Sensitive indicator of muscle No correlation to CK levels AKI or its severity on admission Cannot predict progression to • • Clin Severe >10,000(>15,000) >1000 (>5000)

Chem

Lab Med Med Kinase 2010

AKI & Traumae Serum 2010

Myglobin ?

AKI & Traumae AKI & Traumae AKI & Traumae Rhabdomyolysis Rhabdomyolysis Treatment of AKI caused by • • • • Extracorporeal removal of myoglobin removal of Extracorporeal urine Alkalisation the of Fluids Cause the Treat – – – – – – – Super high flux HD flux high Super HF High volume Bicarbonate +/ Early precipitants Remove Fasciotomy - Diuretics

AKI & Traumae Fluid Fluid Therapy 2011

AKI & Traumae Fluid Fluid Therapy • • • • • Alkalisation of the urine 6L in severe (CK>15,000) the outcome The more fluids per day given the better within 24 hours is amust) the better theoutcome The earlier fluids are given on (i.e.scene) rubble, the worse the AKI Worse the injury time spent/ under – 3L 3L in moderate (CK >5000)

–

(debatable, but

AKI & Traumae Extracorporeal Extracorporeal Myoglobin 2 1 Basnayake Basnayake al et NEJM 2009 (letter) Ling al et J of Injury 2010, Naka et al Critical Care 2005 • • Haemodialysis Super High Flux (1.9m High volume HF with a large Filter – – – Pore size 100kDa 100kDa Pore size exchange high and Blood >300mL/min flows ~50kDa Pore size 2 )

/Filtration

R emoval

AKI & Traumae AKI & Traumae My practice • • • • • CVVHF Oliguria pH Bicarbonate Diuretics UO>2ml/ aiming iv fluid Iv Buffered – – – – – Urea, Na, clearanceTake care withhigh 60ml/kg/ givenParticularlyif we’ve For FB

–

hr stop high volume fluids fluids volume high stop Ca

50kDa in cutoff 50kDa vitro membrane

6.5 - 7

Frusemide

hr

AKI & Traumae • Probable rhabdomyolysis Serum CK >5,000 • • Exclusions: benefit benefit of high /out in strategy Physician decision that risk of fluid overload weighs out Requiring renal replacement therapy • • Check: Adequate intervention ischaemia or other reversible cause that requires specific No compartment syndrome, on

• • • Give: Commence high out/in protocol below Omit or reduce fluid bolus if clinically fluid overloaded Give 4ml/kg IBW

fluid fluid resuscitation and haemodynamic stability

Plasmalyte

- going limb/ muscle

over1h

AKI & Traumae 4 at & 4hrly 12 Hourly - 6 2 hrly hrly hrs

• • • • • • • • • Stop protocol if if CK<5000 Stop protocol and Phosphate CK, Ca Check UEs, pH>7.5 ifarterial Stop Bicarb ( fluid replacement 50ml/ Bicarbonate sodium 1.26% start pH<6 If urine arterialCheck pH and pH urinary clinical status or challenge then fluid If not >2ml/kg/ Urine Output • with output urine hours of last 100% Replacement urine last hours Measure adjusted as needed to needed adjusted as

plasmalyte hr clincian

output ?

Frusemide

) by 50ml/ by )

-

set balance set fluid

hr ( start 20 start

to maintain 100% replacement 100% maintain to - 40mg iv) depending on iv) depending 40mg

plasmalyte hr

and reduce reduce and

AKI & Traumae • • • • • • Local Audit over 6 months with deathNeedrisk of RRT for was strongly associated CK.elevatedcategory associatedwith Trauma (59%), was the common diagnosticmost therapy (RRT). replacementrenal 19 required (27%) AKI. 39 developed(55%) 36 for hadaCKof>5000(52%) days. 3ormore 71 CK >5000.at least of patientshad measurement one • – (Mortality 79% vs. 15%, p< 0.0001). Trauma was less frequent (42%) in patients requiring RRT.

AKI & Traumae Mortality Hospital (Median, Range) CK>5000 after 24h in Fluid (ml) Iv Range) (Median, Peak CK (IU/L) (Median, Range) APACHE score 2 Surgical Medical Trauma Male Sex Range) (Median, Age

(5016 (0 No AKI (n=32) (16 10606 (6 1770 - 31% 63% 81% 9% - 6% 7987) 10 35 - 212200) - 30) 69)

(5055 No RRT

AKI1 (0 (n=20) (17 (7 25% 2444 7845 20% 10% 70% 70% - - 50 7927) 11 - 150000) - 17) 88)

-

3

(5003

(750

(n=19) (24 (10 45851 RRT 79% 2767 26% 32% 42% 74% - 17 53 - 344300) 11000) - - 85) 34)

AKI & Traumae RRT • • • 48h and within the remainder the first of day CK>5000, 6/10 HVHFon received 9 of 10 899 62 CKMedian was peak ( median prescribed dose 72

H

High aemofiltration aemofiltration died ml/kg/h) V

olume

• • • 6 of 9 died 6876 M related topeak CK RRT wasnottemporarily In 7/9 patients, timingof Conventional Volume (median (median Haemodiafiltration Haemodiafiltration edian

35ml/kg/h) peak prescribed prescribed dose

was CKwas

AKI & Traumae HVHF Patient Diagnoses

AKI & Traumae Conclusions • • • • of death associated with severity of underlying diagnosisof with underlyingseverity of deathassociated to beby smallpatient hampered numbers Prospectiveof RM assessment organ failure evidenceof RM of HVHFwithin Despite patients applicationprompt RRTOutcomes those notrequiringinwere good 10% care admissionsof critical in approximatelyof muscle injury evidenceBiochemical

- associated AKI,associated with 90% multi died

- targeted therapy istargeted likely

and highrisk

(15%) -

AKI & Traumae Conclusions AKI following AKI Trauma in – – – – – – and risk Serum phosphate on admission may quantify tissue injury AKI has an impact on mortality patients These are a different epidemiological group to routine AKI ? Role for myoglobin removal ? When Long term outcomes are unclear Early fluid resuscitation • • high in / high out and keep the urine pH>6.0 the and keep out high high in / same the remain risk factors though the

r habdomyolysis

(rel. (rel. rare)

AKI & Traumae Thank you!