Kidney injury after major trauma Traumae John R Prowle MA MSc MD FRCP FFICM AKI & Senior Clinical Lecturer Queen Mary University of London Consultant in Intensive Care and Renal Medicine The Royal London Hospital, Barts Health NHS Trust AKI & Traumae AKI & Traumae Acute Kidney Injury? Kidney Acute • 9449 critically ill trauma patients • AKI 18.1% • Mortality 16.7% v 7.8% Traumae – Older, – female OR 1.6 AKI & – co-morbidities OR 2.7 • AKI as independent risk of mortality – Risk OR 1.68 – Injury OR 1.88 – Failure OR 2.29 London 1940 – 1941 Traumae AKI & Prof. Eric Bywaters (1910-2003) Hammersmith Hospital Bywaters and Beale • Patient had been buried for several hours • On admission …. he looks good apart from swelling of the limb Traumae • His blood pressure falls AKI & • Signs of renal damage soon appear • The urine contains albumin and dark brown granular casts AKI & Traumae Traumatic patients visited in the AE (N=7128) Traumatic patients admitted in the ICU (N=871) Traumae Excluded by Creatinine ≥ 300 µmol/L: 4 patients AKI & Survival less than 24 hours: 9 patients Patients included in the study (N=858) Patient Characteristics Non AKI AKI AKI AKI P value (n=722) Stage I Stage II Stage III (n=79) (n=13) (n=44) Age 41 (27-56) 49 (33-66) 63 (45-78) 47.5 (27-64.5) <0.001 Male (%) 80.9 83.5 84.6 84.1 0.420 NISS 34 (22-50) 34 (22-50) 41 (25-57) 34 (25-50) 0.192 Traumae APACHE II 11 (8-16) 16 (12-19) 16 (13-17) 17 (13-26.5) <0.001 AKI & ICU length of stay (day) 5.5 (3-12) 8 (3-15) 5 (4-8) 8.5 (5.0-23) <0.001 Hospital length of stay 17 (7-37) 21 (8-42) 20 (6-32) 15.5 (6.5-50) 0.630 (day) Mortality 11.8% 20.3% 23.1% 38.6% <0.001 AKI & Traumae Primary Outcome ICU mortality Hospital mortality Predictors Crude OR Adjusted OR Crude OR Adjusted OR Stage I vs Non- 1.56* 1.28 1.95* 1.69 AKI (1.21-2.00) (0.64-2.54) (1.17-3.27) (0.91-3.14) Stage II vs Non- 3.30* 2.42 2.24 1.85 AKI (1.99-5.48) (0.63-9.35) (0.75-6.65) (0.49-7.00) Traumae Stage III vs Non- 5.78* 4.56* 5.41* 3.43* AKI & AKI (4.37-7.64) (2.10-9.92) (2.86-10.22) (1.60-7.34) APACHE II 1.19* 1.05* (1.15-1.23) (1.04-1.06) NISS score 1.06* 1.18* (1.04-1.07) (1.15-1.22) Predicting AKI at admission • Age • Sex • New Injury Severity Score • Admission: Traumae – Creatinine – Lactate AKI & – Phosphate – Creatine Kinease – Blood Pressure – Blood transfusion Predicting AKI 2-3 Traumae AKI & AKI & Traumae RRT Death or AKI-2 Traumae AKI & What causes AKI after trauma? • Hypovolaemic shock • Rhabdomyolysis – Tissue Injury – Iliac Embolisation – Compartment Syndrome • Direct Trauma to the Renal Traumae Tract • Massive Transfusion AKI & • Drugs – Contrast • Abdominal Compartment Syndrome • Sepsis • Surgery AKI & Traumae of AKI of a digressionSepsis: into the mostimportant cause ANNALS OF SURGERY 22(1) · MARCH 2014 Traumae AKI & AKI & Traumae Pathophysiology of Rhabdomyolysis • Rhabdomyolysis – ‘the dissolution of striped (skeletal) muscle’ – Direct sarcolemmic injury • Trauma • Ischaemia reperfusion and inflammation Traumae – Depletion of ATP within the myocyte 2+ AKI & • Unregulated intracellular Ca increase • Destruction of myofibrillar, cytoskeletal and membrane proteins – Release of muscle cell contents • Myoglobin • Conversely fluid loss to muscle compartments – Hypovolaemia – Secondary compartment syndromes Myoglobin and AKI • Myoglobin – Iron and O2 binding protein – 17.8 kDa Traumae – Freely filtered at the glomerulus – Tubular epithelial cells metabolise it AKI & – Appears in urine when concentration is >0.5-1.5mg/dL – Urine becomes red when concentration is >100mg/dL – Myoglobinuria only occurs in the context of rhabdomyolysis Myoglobin and AKI • The toxic effects of myoglobin… – Intra renal vasoconstriction • Tx A2 • Endothelin 1 • TNFα – Direct and tubular injury Traumae • Haem • Catalytic free iron AKI & • Haemoproteins, haemoglobin and myoglobin, once released from cells can cause severe oxidative damage as a consequence of haem redox cycling between ferric and ferryl states that generates radical species that induce lipid peroxidation. – Tubular obstruction – Hypovolaemia Biochemical Markers of Muscle injury and AKI • Serum Creatinine – Cannot predict progression to AKI or its severity on admission – No correlation to CK levels Traumae • Serum Creatine Kinase – Sensitive indicator of muscle AKI & damage • >1000 (>5000) • Severe >10,000 (>15,000) – Peak CK and admission CK correlates to development of AKI* Brancaccio et al Clin Chem Lab Med 2010 de Meijer et al ICM 2003 Serum Myglobin? 2010 Traumae AKI & AKI & Traumae AKI & Traumae Treatment of AKI caused by Rhabdomyolysis • Treat the Cause – Fasciotomy – Remove precipitants • Fluids – Early Traumae – +/-Diuretics AKI & • Alkalisation of the urine – Bicarbonate • Extracorporeal removal of myoglobin – High volume HF – Super high flux HD Fluid Therapy Traumae AKI & 2011 Fluid Therapy • Worse the injury / time spent under rubble, the worse the AKI • The earlier fluids are given (i.e. on scene) the better the outcome– (debatable, but within 24 hours is a must) Traumae • The more fluids per day given the better AKI & the outcome • 6L in severe (CK>15,000) – 3L in moderate (CK >5000) • Alkalisation of the urine Extracorporeal Myoglobin Removal • High volume HF with a large Filter (1.9m2) – Pore size ~50kDa Traumae – Blood flows >300mL/min and high exchange AKI & • Super High Flux Haemodialysis/Filtration 1Ling et al –J of PoreInjury 2010, sizeNaka et al Critical100kDa Care 2005 2Basnayake et al NEJM 2009 (letter) AKI & Traumae My practice • Iv Buffered iv fluid aiming UO>2ml/hr • Diuretics – For FB • Bicarbonate pH 6.5-7 Traumae – Particularly if we’ve given Frusemide AKI & • Oliguria – stop high volume fluids • CVVHF – 60ml/kg/hr 50kDa in vitro cut off membrane – Take care with high clearance – Urea, Na, Ca Probable rhabdomyolysis • Serum CK >5,000 Exclusions: • Requiring renal replacement therapy • Physician decision that risk of fluid overload out weighs benefit of high in /out strategy Traumae Check: AKI & • No compartment syndrome, on-going limb/ muscle ischaemia or other reversible cause that requires specific intervention • Adequate fluid resuscitation and haemodynamic stability Give: • Give 4ml/kg IBW Plasmalyte over 1h • Omit or reduce fluid bolus if clinically fluid overloaded • Commence high out/in protocol below • Measure last hours urine output • 100% Replacement of last hours urine output with plasmalyte Hourly • adjusted as needed to clincian-set fluid balance • Urine Output >2ml/kg/hr? • If not then fluid challenge or Frusemide (start 20-40mg iv) depending on at 2 hrs clinical status & 4hrly • Check urinary pH and arterial pH Traumae • If urine pH<6 start 1.26% sodium Bicarbonate 50ml/hr and reduce replacement fluid (plasmalyte) by 50ml/hr to maintain 100% replacement 4-6 hrly AKI & • Stop Bicarb if arterial pH>7.5 • Check UEs, CK, Ca and Phosphate • Stop protocol if CK<5000 12 hrly Local Audit over 6 months • 71 patients had at least one CK measurement of >5000. • 36 (52%) had a CK of >5000 for 3 or more days. • 39 (55%) developed AKI. • 19 (27%) required renal replacement therapy (RRT). Traumae • Trauma (59%), was the most common diagnostic AKI & category associated with elevated CK. • Trauma was less frequent (42%) in patients requiring RRT. • Need for RRT was strongly associated with risk of death – (Mortality 79% vs. 15%, p< 0.0001). No AKI AKI 1-3 RRT (n=32) No RRT (n=19) (n=20) Age 35 50 53 (Median, Range) (16-69) (17-88) (24-85) Male Sex 81% 70% 74% Trauma 63% 70% 42% Medical 31% 10% 32% Surgical 6% 20% 26% APACHE 2 score 10 11 17 Traumae (Median, Range) (6-30) (7-17) (10-34) AKI & Peak CK (IU/L) 10606 7845 45851 (Median, Range) (5016-212200) (5055-150000) (5003-344300) Iv Fluid (ml) in 24h 1770 2444 2767 after CK>5000 (0-7987) (0-7927) (750-11000) (Median, Range) Hospital 9% 25% 79% Mortality RRT High Volume Conventional Volume Haemofiltration Haemodiafiltration (median prescribed dose 72 (median prescribed dose ml/kg/h) 35ml/kg/h) Traumae • 6/10 received HVHF on • In 7/9 patients, timing of the first day of CK>5000, RRT was not temporarily AKI & and the remainder within related to peak CK 48h • Median peak was CK • Median peak CK was 62 6876 899 • 6 of 9 died • 9 of 10 died AKI & Traumae HVHF Patient Diagnoses Patient HVHF Conclusions • Biochemical evidence of muscle injury in approximately 10% of critical care admissions • Outcomes were good in those not requiring RRT (15%) • Despite prompt application of HVHF in patients with evidence of RM-associated AKI, 90% died with multi- Traumae organ failure AKI & • Prospective assessment of RM-targeted therapy is likely to be hampered by small patient numbers and high risk of death associated with severity of underlying diagnosis Conclusions AKI in Trauma – These are a different epidemiological group to routine AKI patients • though the risk factors remain the same – AKI has an impact on mortality – Serum phosphate on admission may quantify tissue injury Traumae and risk AKI & AKI following rhabdomyolysis (rel. rare) – Early fluid resuscitation • high in / high out and keep the urine pH>6.0 – Long term outcomes are unclear – ? Role for myoglobin removal ? When AKI & Traumae Thank you! Thank .