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Perioperative Renal Failure: Can we avoid the Gamcath  ? Blair Schwartz January 26 th, 2010.

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Presentation on theme: "Perioperative Renal Failure: Can we avoid the Gamcath  ? Blair Schwartz January 26 th, 2010."— Presentation transcript:

1 Perioperative Renal Failure: Can we avoid the Gamcath  ? Blair Schwartz January 26 th, 2010

2 Objectives 1. Review pathophysiology and diagnostic criteria for perioperative renal failure 2. Review risk factors for the development of perioperative renal failure 3. Discuss potential methods for preventing perioperative renal failure and thus avoid the dreaded (by some) Gamcath .

3 The definition conundrum The major problem in “acute renal failure” research is one of lack of clear definition The major problem in “acute renal failure” research is one of lack of clear definition Over 35 different definitions exist in the literature Over 35 different definitions exist in the literature Thus getting a handle on the problem is difficult Thus getting a handle on the problem is difficult

4 Solving things the Charlton Heston way…

5 The Acute Kidney Injury Network “An abrupt (within 48 hours) reduction in kidney function currently defined as an absolute increase in serum creatinine of more than or equal to 0.3 mg/dl (26.4 mmol/l), a percentage increase in serum creatinine of more than or equal to 50% (1.5-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5 ml/kg per hour for more than six hours).” “An abrupt (within 48 hours) reduction in kidney function currently defined as an absolute increase in serum creatinine of more than or equal to 0.3 mg/dl (26.4 mmol/l), a percentage increase in serum creatinine of more than or equal to 50% (1.5-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5 ml/kg per hour for more than six hours).” Must be in the context of adequate hydration Must be in the context of adequate hydration

6 The new RIFLE Criteria Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network:report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007 Mar 1;11(2):R31. RRT is automatically stage 3

7 Problems with the criteria? Urine output not solely a reflection of renal function Urine output not solely a reflection of renal function Volume status Volume status Serum Creatinine is often slow to respond and thus not an ideal marker Serum Creatinine is often slow to respond and thus not an ideal marker

8

9 Future fixes… Neutrophil Gelatinase- Assoc. Lipocalin (NGAL) Levels in blood and urine rise within a few hours after injury Cystatin C Absorbed by kidney, but not secreted Rises one day before Cr Interleukin 18 Produced by caspase-I which is implicted in pathogenesis of ARF Have been shown to predict AKI severity in post-op hearts

10 Prevalence of perioperative RF Multitude of definitions makes determining the prevalence of RF very difficult Multitude of definitions makes determining the prevalence of RF very difficult Cardiac Surgery Cardiac Surgery AKI 7.7-11.4% AKI 7.7-11.4% CRRT <1 -5% CRRT <1 -5% Gastric Bypass Gastric Bypass AKI 8.5% AKI 8.5% Non-Cardiac Surgery Non-Cardiac Surgery GFR < 50 ml/min 0.8% GFR < 50 ml/min 0.8% AAA AAA AKI 15-46% AKI 15-46% OLT OLT AKI 48-94% AKI 48-94% CRRT 8-17% CRRT 8-17%

11 Prevalence unclear, importance settled. Emerging evidence that AKI, ARF, Renal failure in the perioperative period changes outcomes. Emerging evidence that AKI, ARF, Renal failure in the perioperative period changes outcomes. 7-10 fold increase in risk-adjusted odds of death over patients without AKI 7-10 fold increase in risk-adjusted odds of death over patients without AKI Mortality rates at 30 days, 60 days and 1 year was increased amongst the 15,000 patients followed after non-cardiac surgery amongst those with AKI Mortality rates at 30 days, 60 days and 1 year was increased amongst the 15,000 patients followed after non-cardiac surgery amongst those with AKI 2.7% to 15%, 5.1-17%, 15%-31% 2.7% to 15%, 5.1-17%, 15%-31% Similar numbers for OLT and AAA Similar numbers for OLT and AAA Cardiac Surgery: Cardiac Surgery: Mortality rate 0.8% without renal dysfunction Mortality rate 0.8% without renal dysfunction 9.5% with AKI 9.5% with AKI 44.4% with renal failure and RRT need 44.4% with renal failure and RRT need

12 So… Periop RF is common Periop RF is common Periop RF is associated with poor outcome Periop RF is associated with poor outcome Associated temporally with an identifiable event Associated temporally with an identifiable event In theory…. Perhaps a target for prevention!!! In theory…. Perhaps a target for prevention!!!

13 But… To do so, must be able to identify those at risk and/or risk factors for periop AKI Have a feasible strategy And then question as to whether AKI is the cause of the morbidity/mortality or the result?

14 Assuming we can intervene… Can analyze risk factors: Can analyze risk factors: Preoperative factors Preoperative factors Intraoperative factors Intraoperative factors Postoperative factors Postoperative factors

15 Preoperative Risk Factors Kheterpal Kheterpal 15,000 patients with normal preoperative RF undergoing non-cardiac surgery 15,000 patients with normal preoperative RF undergoing non-cardiac surgery identified the following independent risk factors for post-op RF: identified the following independent risk factors for post-op RF: Age Age Emergency Surgery Emergency Surgery BMI > 33 BMI > 33 Peripheral Vascular Occlusive Disease Peripheral Vascular Occlusive Disease COPD needing bronchodilator therapy COPD needing bronchodilator therapy

16 Always with the hearts

17 Summary… From a patient perspective, the more comorbid illness associated with RF, the more RF postop From a patient perspective, the more comorbid illness associated with RF, the more RF postop Thus we are ALREADY getting the information we need to prognosticate Thus we are ALREADY getting the information we need to prognosticate In fact an RCRI >2 has been shown to be an independent predictor In fact an RCRI >2 has been shown to be an independent predictor Granted, Creat >177 and DM on insulin are included in the RCRI and are known ARF RF Granted, Creat >177 and DM on insulin are included in the RCRI and are known ARF RF

18 More preop things… “Maintenance of adequate intravascular volume” “Maintenance of adequate intravascular volume” Perhaps one of the most loaded statements in all of medicine, but certainly important Perhaps one of the most loaded statements in all of medicine, but certainly important Uncorrected hypovolemia can well lead to pre-renal AKI and in the context of further perioperative stress can lead to ischemic ATN Uncorrected hypovolemia can well lead to pre-renal AKI and in the context of further perioperative stress can lead to ischemic ATN Thus an important part of the perioperative consultation Thus an important part of the perioperative consultation Particularly in emergent surgery, and definitely in hip fractures!!!! Particularly in emergent surgery, and definitely in hip fractures!!!!

19 Volume et al… Unclear what the best way to determine this is… Unclear what the best way to determine this is… History History Physical exam Physical exam Swann? Swann? All methods have their limitations, thus likely a combination of some/all of the above All methods have their limitations, thus likely a combination of some/all of the above

20 Peri-operative Issues Examine for volume status Examine for volume status Be cognizant of NPO duration, frequent cancellations and ensure adequate maintenance fluids Be cognizant of NPO duration, frequent cancellations and ensure adequate maintenance fluids What to do with diuretics, both pre-op, day of the OR… What to do with diuretics, both pre-op, day of the OR… Be alert to patients at risk and the routine prescription of NSAIDs with anaesthesia protocols Be alert to patients at risk and the routine prescription of NSAIDs with anaesthesia protocols Keep a keen eye as well for all other nephrotoxins Keep a keen eye as well for all other nephrotoxins

21 Fluid of choice? The never ending crystalloid/colloid debate The never ending crystalloid/colloid debate Insufficient evidence to suggest one over the other Insufficient evidence to suggest one over the other NB. Pentaspan and some other HES associated with RF (and coagulopathies) over maximum suggested doses…controversial NB. Pentaspan and some other HES associated with RF (and coagulopathies) over maximum suggested doses…controversial Will this be fixed with voluven? Will this be fixed with voluven?

22 What about optimizing renal perfusion? Renal perfusion autoregulates between MAP 80- 160 mmHg to maintain stable GFR Renal perfusion autoregulates between MAP 80- 160 mmHg to maintain stable GFR Unclear what ideal MAP is to “protect” kidneys Unclear what ideal MAP is to “protect” kidneys In septic shock, 85 was NOT better than 65 In septic shock, 85 was NOT better than 65 One study used doppler U/S to assess renal resistive indices to individualize MAP goals One study used doppler U/S to assess renal resistive indices to individualize MAP goals Taking MAP from 65-75 mmHg led to increased UO an decreased resistance Taking MAP from 65-75 mmHg led to increased UO an decreased resistance No improvement when MAP from 75-85 mmHg No improvement when MAP from 75-85 mmHg

23 Perfusion Issues What is the optimal perfusion pressure in people with chronic HTN? RAS? What is the optimal perfusion pressure in people with chronic HTN? RAS? What to do with BP Meds: What to do with BP Meds: HCTZ… addressed earlier HCTZ… addressed earlier ACE/ARB/DRI… ACE/ARB/DRI… Alters renal regulation Alters renal regulation Associated with post-induction hypotension Associated with post-induction hypotension No clear renal outcome data periop No clear renal outcome data periop Individualize periop RAAS agent management Individualize periop RAAS agent management

24 What about the Surgeons? Cardiac Surgery (yes again…) Cardiac Surgery (yes again…) Duration of pump run Duration of pump run Risk increases over 100 minutes Risk increases over 100 minutes ? Lack of pulsatile flow as aetiology ? Lack of pulsatile flow as aetiology More data to come from long term analysis of continuous flow HeartMate 2 VADS More data to come from long term analysis of continuous flow HeartMate 2 VADS What about the role of Off-pump bypass What about the role of Off-pump bypass Lower incidence of AKI (and other CPB complications) Lower incidence of AKI (and other CPB complications) But…recent concerns about cardiac outcomes But…recent concerns about cardiac outcomes

25 Blame the Surgeons AAA AAA Related to duration of cross-clamp Related to duration of cross-clamp Can be technical as well if they “bag” the renals Can be technical as well if they “bag” the renals Suggestion of improved outcomes with endovascular repairs Suggestion of improved outcomes with endovascular repairs Thus to be considered when risk stratifying preoperatively Thus to be considered when risk stratifying preoperatively

26 Can we blame general surgeons too? Laparoscopy Laparoscopy Renal blood flow and function are reduced during pneumoperitoneum Renal blood flow and function are reduced during pneumoperitoneum As intrabdominal pressure increases, U/O decreases…. As intrabdominal pressure increases, U/O decreases…. Form of abdominal compartment syndrome Form of abdominal compartment syndrome Likely safe under 15 Likely safe under 15 Case reports of renal failure post-laparoscopy exist Case reports of renal failure post-laparoscopy exist ? Role of hypovolemia as contributor ? Role of hypovolemia as contributor Can consider gasless laparoscopy in those at high risk!!! Can consider gasless laparoscopy in those at high risk!!! ?RAS ?RAS

27 Yet another hit on transfusion Independently associated with increased risk of post-op AKI in OLT patients. Independently associated with increased risk of post-op AKI in OLT patients. As always… As always… ? Cause/effect ? Cause/effect

28 So now what? If we identify patients at risk… And mitigate all that is controllable… Is there any targeted therapies we can try to decrease the risk of periop RF?

29 Good old fashioned Lasix “inhibition of renal tubular oxygen consumption” “inhibition of renal tubular oxygen consumption” Animal models…?mechanism Animal models…?mechanism Would it prevent ischemia during times of low delivery? Would it prevent ischemia during times of low delivery? Like cross clamping! Like cross clamping! Has NOT been shown to decrease perioperative AKI Has NOT been shown to decrease perioperative AKI Will increase urine output, convert to non-oliguric, which may be useful Will increase urine output, convert to non-oliguric, which may be useful But no change in hard endpoints But no change in hard endpoints

30 “Renal Dose” Dopamine Has been extensively studied… Will increase urine output; which may not be a bad thing Has numerous side effects Does NOT protect patients from AKI

31 What if we’re NOT afraid of the Gamcath  ? Prophylactic Dialysis Prophylactic Dialysis Has been evaluated in extremely high risk surgeries; case control Has been evaluated in extremely high risk surgeries; case control OLT in patients with borderline renal function preop OLT in patients with borderline renal function preop Did not decrease rates of perioperative AKI Did not decrease rates of perioperative AKI But useful to manage complications like hypervolemia, acidosis and hyperkalemia But useful to manage complications like hypervolemia, acidosis and hyperkalemia

32 Is there any hope?

33 Fenoldopam!!! Dopamine-I receptor agonist approved for the treatment of hypertensive emergencies Dopamine-I receptor agonist approved for the treatment of hypertensive emergencies

34 Background Selective short-acting Dopamine-1 agonist Selective short-acting Dopamine-1 agonist Smooth-muscle relaxation Smooth-muscle relaxation Renal vasodilatation Renal vasodilatation Tubular sodium reabsorption Tubular sodium reabsorption Data existing is all over the map Data existing is all over the map Previous large study was negative, but control group was dopamine! Also used lower dose. Previous large study was negative, but control group was dopamine! Also used lower dose. Aim is confirm effectiveness of fenoldopam 0.1  g/kg/min for preserving RF in patients undergoing elective heart surgery who are at high risk for postop AKI Aim is confirm effectiveness of fenoldopam 0.1  g/kg/min for preserving RF in patients undergoing elective heart surgery who are at high risk for postop AKI

35 Methods Inclusion Criteria: Inclusion Criteria: ONE of the following RF (and elective heart surgery) ONE of the following RF (and elective heart surgery) Creat >1.5 mg/dl (132  mol/L) Creat >1.5 mg/dl (132  mol/L) Age >70 Age >70 DM on insulin DM on insulin Repeat sternotomy Repeat sternotomy Exclusion Criteria: Exclusion Criteria: <18 y/o <18 y/o Preop dialysis or inotropes Preop dialysis or inotropes Allergy to fenoldopam Allergy to fenoldopam

36 Methods Usual cardiac surgery technique was used Usual cardiac surgery technique was used No aprotinin given No aprotinin given Standard criteria to give vasopressors, fluid and inotropes defined Standard criteria to give vasopressors, fluid and inotropes defined Computer generated randomization to fenoldopam vs placebo, investigators, clinicians and patients blinded to assignment. Computer generated randomization to fenoldopam vs placebo, investigators, clinicians and patients blinded to assignment. Primary Endpoint: AKI, post-op creat > 2 mg/dl (177  mol/L) on day 1 or 2 Primary Endpoint: AKI, post-op creat > 2 mg/dl (177  mol/L) on day 1 or 2

37 Results

38 Results

39 Results CRRT started in 0/95 patients in the fenoldopam group, compared to 8/98 (8.2%) in placebo CRRT started in 0/95 patients in the fenoldopam group, compared to 8/98 (8.2%) in placebo So maybe we can avoid the Gamcath after all? So maybe we can avoid the Gamcath after all?

40 Other stuff? Anaritide Anaritide recombinant human atrial natriuretic peptide, recombinant human atrial natriuretic peptide, an infusion of 50 ng/kg/min decreased the probability of dialysis in a study of postcardiac surgical heart failure patients with AKI. an infusion of 50 ng/kg/min decreased the probability of dialysis in a study of postcardiac surgical heart failure patients with AKI.

41 Take Home Messages Periop AKI is common and serious Periop AKI is common and serious Judicious management of volume and pressure is important Judicious management of volume and pressure is important Be aware of high risk patients and try to avoid doing silly things to them Be aware of high risk patients and try to avoid doing silly things to them Await further studies on Fenoldopam and anaritide. Await further studies on Fenoldopam and anaritide.

42 Questions?

43 References Zanardo G, Michielon P, Paccagnella A, et al. Acute renal failure in the patient undergoing cardiac operation. Prevalence, mortality rate, and main risk factors. J Thorac Cardiovasc Surg. 1994;107:1489–1495. Zanardo G, Michielon P, Paccagnella A, et al. Acute renal failure in the patient undergoing cardiac operation. Prevalence, mortality rate, and main risk factors. J Thorac Cardiovasc Surg. 1994;107:1489–1495. Thakar CV, Arrigain S, Worley S, et al. A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol. 2005;16:162–168. Thakar CV, Arrigain S, Worley S, et al. A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol. 2005;16:162–168. Kheterpal S, Tremper KK, Englesbe MJ, et al. Predictors of postoperative acute renal failure after noncardiac surgery in patients with previously normal renal function. Anesthesiology. 2007;107:892–902. Kheterpal S, Tremper KK, Englesbe MJ, et al. Predictors of postoperative acute renal failure after noncardiac surgery in patients with previously normal renal function. Anesthesiology. 2007;107:892–902. Thakar CV, Kharat V, Blanck S, et al. Acute kidney injury after gastric bypass surgery. Clin J Am Soc Nephrol. 2007;2:426–430. Thakar CV, Kharat V, Blanck S, et al. Acute kidney injury after gastric bypass surgery. Clin J Am Soc Nephrol. 2007;2:426–430. Barratt J, Parajasingam R, Sayers RD, et al. Outcome of acute renal failure following surgical repair of ruptured abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2000;20:163–168. Barratt J, Parajasingam R, Sayers RD, et al. Outcome of acute renal failure following surgical repair of ruptured abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2000;20:163–168. Sward K, Valsson F, Odencrants P et al. Recombinant human atrial natriuretic peptide in ischemic acute renal failure: a randomized placebo-controlled trial. Critical Care Medicine 2004 Jun; 32(6): 1310–1315. Sward K, Valsson F, Odencrants P et al. Recombinant human atrial natriuretic peptide in ischemic acute renal failure: a randomized placebo-controlled trial. Critical Care Medicine 2004 Jun; 32(6): 1310–1315. Kellum JA & Decker M. Use of dopamine in acute renal failure: a meta-analysis. Critical Care Medicin 2001 Aug; 29(8): 1526–1531 Kellum JA & Decker M. Use of dopamine in acute renal failure: a meta-analysis. Critical Care Medicin 2001 Aug; 29(8): 1526–1531 Deruddre S, Cheisson G, Mazoit JX et al. Renal arterial resistance in septic shock: effects of increasing mean arterial pressure with norepinephrine on the renal resistive index assessed with Doppler ultrasonography. Intensive Care Medicine 2007 May 8 Deruddre S, Cheisson G, Mazoit JX et al. Renal arterial resistance in septic shock: effects of increasing mean arterial pressure with norepinephrine on the renal resistive index assessed with Doppler ultrasonography. Intensive Care Medicine 2007 May 8


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