Preven'ng AKI. Lessons from Contrast-associated AKI It s all about urine output

Transcription

1 Preven'ng AKI Lessons from Contrast-associated AKI It s all about urine output

2 CASE A 76 y/o male comes to the ED complaining of substernal crushing chest pain. The pain started a few hours ago while he was removing snow from his driveway. He says that he has had similar pain with exer'on in the past but it never lasted this long or was as severe. He has not had any rou'ne medical care and takes no medica'ons. Exam: slightly diaphore'c 80 kg man, BP 160/90, HR 88, O 2 sat 95%, lungs without rales, RR, no murmur/rub, abdomen sow, NT, extremi'es with 2+ pulses, no edema. Lab: Hgb 11.0, WBC 8,800, Na 140, K 3.9, TCO2 24, Cl 98, crea'nine 1.5, BUN 20, glucose (non fas'ng) 120, Troponin I 1.0, EKG T wave inversions in I,L and lateral limb leads, no ST wave changes. He is given ASA and nitroglycerin in ED and started on heparin qb. His pain subsides temporarily but returns by the next morning. Cycling of troponins are consistent with ongoing ischemia. He is diagnosed with unstable angina and a lew heart cath is planned.

3 Contrast-associated acute kidney injury (CA-AKI? CA-AKI, regardless of defini'on, is associated with: Acute: mortality, need for dialysis Medium: MACE Long term: mortality, deteriora'on in kidney func'on, dialysis Fear of CA-AKI deprives many pa'ents with chronic kidney disease life preserving interven'ons. CA-AKI once established is not reversible by medical therapy. It is likely that complete recovery never occurs despite return of crea'nine to baseline levels. Preven'on of CA-AKI is our best approach. We have not got a reliable strategy to prevent CI-AKI.

4 Modeling Risk of AKI in Angiography and Surgery Clinical Applica'ons Therapeu'c Measures Research Applica'ons Informed Decision-Making Plan resource u'liza'on Assess quality of care Plan follow-up care Ins'tute preventa've strategies Early treatment Compare efficacy of treatments Safer techniques Surgical Contrast Biomarker discovery/ valida'on Novel therapies Early dialy'c interven'on Study recovery from injury Adopted from Thakar, Am J Kid Dis 2010

5 Guidelines in Cardiology 1. Iden'fy risk by calcula'on of GFR and risk models. 2. Give adequate preparatory hydra'on. 3. Minimize the amount of contrast used: suggested upper limit based upon baseline GFR JACC 2011

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7 Predic'on Models in Contrast Induced At least 12 models AKI Some use variables from the procedure itself such as the amount of contrast administered

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9 MEHRAN RISK MODEL %

10 What is adequate preparatory hydra'on? Considered the standard of care for high risk pa'ents exposed to contrast. [Perhaps all high risk pa'ents for any AKI.] Ques'ons remaining: Timing of fluids: 12h before and awer, 6h before and awer, 1h before and 4h awer. Type of fluid: oral vs IV; water vs salt containing. Type of salt solu'on: sodium chloride vs sodium bicarbonate. Poseidon Trial: rate of IV fluids based on LVEDP 1 Brar et al. Lancet 2014

11 Mechanisms of contrast Ischemia/hypoxemia nephrotoxicity CM reduce renal blood flow, par'cularly in the medulla of the kidney. Inhibi'on of NO synthesis à vasoconstric'on How? does Viscosity adequate > osmolality of preparatory contrast media hydra'on Cell toxicity affect these pathologic mechanisms? CM are taken up by renal tubule cells and interfere with mitochondria, leading to the release of s'muli for the cell to undergo apoptosis. Increased genera'on of ROS.

12 Hypothesis: it is about urine flow rate Volume reten'on Reduce vasoconstric've elements SNS, RAS,?endothelin that exacerbate contrast induced renal ischemia. A high urine flow rate will: Dilute the concentra'on of contrast within the tubule lumen. Decrease contact 'me between contrast media and renal tubule cell. Other mechanisms? Increase an'-oxidant mechanisms within the kidney Increase in medullary blood flow and medullary po2 Prostaglandin mediated Impaired in those with endothelial dysfunc'on (aged, diabetes)

13 Yoshioka et al, Kidney Int 1992

14 Water diuresis induces an increase in medullary po2 TIME COURSE Prasad and Epstein, Kidney Int 1999 Tumkur et al, Kidney Int 2006

15 Fluid is beber than no fluid?

16 Saline vs No Saline in STEMI/PCI 0.9% NS at 1 ml/kg/h x 12 post PCI Luo et al. Intern Med 2014

17 Saline vs No Saline in STEMI/PCI 0.9% 1 ml/kg/h x Saline No Saline Incidence % AKI Dialysis Mortality Jurado-Roman et al. Am J Cardiology 2015

18 30 Circ Cardiovas Interv 2011 Incidence of CIN % < >1081 Volume of 0.9% Saline

19 PRINCE Study Furosemide 1 mg/kg up to 100 mg Stevens et al, JACC 1999

20 Matched Hydra'on Study Protocol Pre-procedure Procedure Post- procedure 600 Urine flow rate (ml/h) Foley Catheter Prime ( 250 ml) Furosemide (0.25 mg/kg) 100 Con'nuous, real 'me replacement of urine output with NS PaHent ready for Time (minutes) procedure when urine flow rate is 300 ml/h

21 CI-AKI Incidence in Prospec've Studies Standard of Care 39.0% Matched hydra'on -74% 18.0% -79% -72% -78% 25.0% 25.0% -88% 13.0% 4.6% 2.7% 7.0% 5.0% 5.0% MYTHOS REMEDIAL II AKIGUARD PROTECT-TAVI CI-AKI & TAVI 77% Weighted Average Decrease of CI-AKI using matched hydra'on in Prospec've Studies Marenzi. MYTHOS JACC Cardiovasc Interv BarbanH PROTECT-TAVI JACC: Cardiovascular Interven9ons Briguori. REMEDIAL II Circula9on VisconH EuroInterven9on Usmiani. AKIGUARD. J Cardiovasc Med 2015.

22 Comparison of urine outputs in PRINCE vs. MYTHOS Marenzi et al. JACC Cardiovasc Interv. 2012;5(1):90-7. Stevens MA et al. J Am Coll Cardiol :

23 Matched hydra'on in High-Risk Pa'ents for Contrast-Induced Acute Kidney Injury Briguori followed 400 highrisk pa'ents treated with matched hydra'on. Reported rela'onship between urine output profile and the development of AKI. High urine output key (>450 ml/hr at peak) = no CIAKI In the few pa'ents with low urine output response, clinicians may consider being more cau'ous with contrast usage. Failure to increase urine output a@er a bolus of NS and furosemide is a pre-emp9ve Furosemide Stress Test Briguori C, et al.. Am Heart J

24 Prophylaxis Induce a high urine flow rate. Load with volume (isotonic) = suppress vasopressin and other vasoac've mediators Remove diure'cs Excep'on: matched hydra'on therapy Limit dura'on of NPO status Encourages oral water before and awer contrast exposure = suppress vasopressin

25 What addi'onal interven'ons might have reduced likelihood of AKI? An'oxidant: N-acetylcysteine: most large trials found no benefit Bicarbonate: meta-analysis suggest benefit but the largest trials with the most power found no benefit. Both are being studied in PRESERVE, a 2x2 randomized trial of 8600 high risk pa'ents undergoing coronary and non-coronary arteriographyw.

26 Prophylaxis Sta'n therapy Con'nue if already on therapy Start if not on therapy Remote ischemic precondi'oning (RIPC) Equivocal results. No apparent harm. Adds minutes to procedure.

27 CASE Started on 0.9% sodium chloride at 1 ml/kg/h and taken to the cath lab 3 hours later. Found to have 95% stenosis in distal LAD. DES stent placed with good flow. Total amount of contrast 110 ml 0.9% sodium chloride con'nued for 6 hours at 1 ml/kg/h. Crea'nine awer 6 hours 1.62 mg/dl (baseline 1.51 mg/dl) Pa'ent discharged home.

28 Does he have AKI? No Doesn t meet 0.3 mg/dl criteria Urine output? Not recorded Yes But it hasn t been 48 hours Crea'nine increasing despite volume load. Is he in posi've balance?

29 When to Measure? Most pa'ents discharged on the day following angiography. CI-AKI = 0.5 mg/dl increase Davidson et al, (unpublished)

30 How to Address Short Term Admission Status A 5% rela've increase in crea'nine at 12 hours was predic've of CI-AKI with an AUC of High risk pa'ents with CKD Hydra'on with 12 h NS before and awer CM CI-AKI = 25% increase at 48 hr Ribichini et al Am J Med 2010

31 Post contrast exposure Look for AKI Measure kidney func'on Biomarkers (NGAL, KIM-1, Nephrocheck, etc) not sensi've/specific enough In most trials with pre PCI volume administra'on, crea'nine falls or stays the same at 24 hours. Evidence supports a 12 h serum crea'nine with a 5-10% increase may be predic've of AKI.

32 Protocol for Preven'on of CA-AKI ACC/AHA/SCAI > Guidelines

33 PREVENTION OF AKI Or, an'cipa'ng an episode of acute kidney injury? So, planning on roaming the neighborhood with some of your buddies today?