Perioperative Renal Perioperative Renal Failure: Can we avoid the Failure: Can we avoid the

GamcathGamcath??

Blair SchwartzBlair Schwartz

January 26January 26thth, 2010, 2010

ObjectivesObjectives

1.1. Review pathophysiology and diagnostic Review pathophysiology and diagnostic criteria for perioperative renal failurecriteria for perioperative renal failure

2.2. Review risk factors for the development Review risk factors for the development of perioperative renal failureof perioperative renal failure

3.3. Discuss potential methods for Discuss potential methods for preventing perioperative renal failure preventing perioperative renal failure and thus avoid the dreaded and thus avoid the dreaded (by some)(by some) GamcathGamcath..

The definition The definition conundrumconundrum

The major problem in The major problem in “acute renal failure” “acute renal failure” research is one of research is one of lack of clear lack of clear definitiondefinition

Over 35 different Over 35 different definitions exist in definitions exist in the literaturethe literature

Thus getting a handle Thus getting a handle on the problem is on the problem is difficultdifficult

Solving things the Charlton Solving things the Charlton Heston way…Heston way…

The Acute Kidney Injury The Acute Kidney Injury NetworkNetwork

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

Must be in the context of adequate Must be in the context of adequate hydrationhydration

The new RIFLE CriteriaThe 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

Problems with the Problems with the criteria?criteria?

Urine output not solely a reflection of Urine output not solely a reflection of renal functionrenal function Volume statusVolume status

Serum Creatinine is often slow to respond Serum Creatinine is often slow to respond and thus not an ideal markerand thus not an ideal marker

Future fixes…Future fixes… Neutrophil Neutrophil

Gelatinase-Assoc. Gelatinase-Assoc. Lipocalin (NGAL)Lipocalin (NGAL) Levels in blood and Levels in blood and

urine rise within a urine rise within a few hours after injuryfew hours after injury

Cystatin CCystatin C Absorbed by kidney, Absorbed by kidney,

but not secretedbut not secreted Rises one day before CrRises one day before Cr

Interleukin 18Interleukin 18 Produced by caspase-Produced by caspase-

I which is implicted I which is implicted in pathogenesis of in pathogenesis of ARFARF

Have been shown to predict AKI severity in post-op hearts

Prevalence of Prevalence of perioperative RFperioperative RF

Multitude of definitions makes Multitude of definitions makes determining the prevalence of RF very determining the prevalence of RF very difficultdifficult Cardiac Surgery Cardiac Surgery

AKI 7.7-11.4%AKI 7.7-11.4% CRRT <1 -5%CRRT <1 -5%

Gastric BypassGastric 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%

AAAAAA AKI 15-46%AKI 15-46%

OLTOLT AKI 48-94%AKI 48-94% CRRT 8-17%CRRT 8-17%

Prevalence unclear, Prevalence unclear, importance settled.importance settled.

Emerging evidence that AKI, ARF, Renal Emerging evidence that AKI, ARF, Renal failure in the perioperative period changes failure in the perioperative period changes outcomes.outcomes. 7-10 fold increase in risk-adjusted odds of death 7-10 fold increase in risk-adjusted odds of death

over patients without AKIover patients without AKI Mortality rates at 30 days, 60 days and 1 year was Mortality rates at 30 days, 60 days and 1 year was

increased amongst the 15,000 patients followed increased amongst the 15,000 patients followed after non-cardiac surgery amongst those with AKIafter 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 AAASimilar numbers for OLT and AAA Cardiac Surgery:Cardiac Surgery:

Mortality rate 0.8% without renal dysfunctionMortality rate 0.8% without renal dysfunction 9.5% with AKI9.5% with AKI 44.4% with renal failure and RRT need44.4% with renal failure and RRT need

So…So…

Periop RF is Periop RF is commoncommon

Periop RF is Periop RF is associated with poor associated with poor outcomeoutcome

Associated Associated temporally with an temporally with an identifiable eventidentifiable event

In theory…. In theory…. Perhaps a target Perhaps a target for prevention!!!for prevention!!!

But…But… To do so, must be To do so, must be

able to identify those able to identify those at risk and/or risk at risk and/or risk factors for periop factors for periop AKIAKI

Have a feasible Have a feasible strategystrategy

And then question And then question as to whether AKI as to whether AKI is the cause of the is the cause of the morbidity/mortalitmorbidity/mortality or the result?y or the result?

Assuming we can Assuming we can intervene…intervene…

Can analyze risk Can analyze risk factors:factors: Preoperative Preoperative

factorsfactors Intraoperative Intraoperative

factorsfactors Postoperative Postoperative

factorsfactors

Preoperative Risk Preoperative Risk FactorsFactors

Kheterpal Kheterpal 15,000 patients with normal 15,000 patients with normal

preoperative RF undergoing non-preoperative RF undergoing non-cardiac surgery cardiac surgery

identified the following independent identified the following independent risk factors for post-op RF:risk factors for post-op RF: AgeAge Emergency SurgeryEmergency Surgery BMI > 33BMI > 33 Peripheral Vascular Occlusive DiseasePeripheral Vascular Occlusive Disease COPD needing bronchodilator therapyCOPD needing bronchodilator therapy

Always with the heartsAlways with the hearts

Summary…Summary…

From a patient perspective, the more From a patient perspective, the more comorbid illness associated with RF, comorbid illness associated with RF, the more RF postopthe more RF postop Thus we are ALREADY getting the Thus we are ALREADY getting the

information we need to prognosticateinformation we need to prognosticate In fact an RCRI >2 has been shown to In fact an RCRI >2 has been shown to

be an independent predictorbe an independent predictor Granted, Creat >177 and DM on insulin Granted, Creat >177 and DM on insulin

are included in the RCRI and are known are included in the RCRI and are known ARF RFARF RF

More preop things…More preop things…

““Maintenance of adequate intravascular Maintenance of adequate intravascular volume”volume” Perhaps one of the most loaded statements Perhaps one of the most loaded statements

in all of medicine, but certainly importantin all of medicine, but certainly important Uncorrected hypovolemia can well lead to Uncorrected hypovolemia can well lead to

pre-renal AKI and in the context of further pre-renal AKI and in the context of further perioperative stress can lead to ischemic perioperative stress can lead to ischemic ATNATN

Thus an important part of the perioperative Thus an important part of the perioperative consultationconsultation

Particularly in emergent surgery, and definitely Particularly in emergent surgery, and definitely in hip fractures!!!!in hip fractures!!!!

Volume et al…Volume et al…

Unclear what the best way to Unclear what the best way to determine this is…determine this is… HistoryHistory Physical examPhysical exam Swann?Swann?

All methods have their limitations, All methods have their limitations, thus likely a combination of some/all thus likely a combination of some/all of the above of the above

Peri-operative IssuesPeri-operative Issues

Examine for volume statusExamine for volume status Be cognizant of NPO duration, frequent Be cognizant of NPO duration, frequent

cancellations and ensure adequate cancellations and ensure adequate maintenance fluidsmaintenance fluids

What to do with diuretics, both pre-op, day of What to do with diuretics, both pre-op, day of the OR…the OR…

Be alert to patients at risk and the routine Be alert to patients at risk and the routine prescription of NSAIDs with anaesthesia prescription of NSAIDs with anaesthesia protocolsprotocols Keep a keen eye as well for all other nephrotoxinsKeep a keen eye as well for all other nephrotoxins

Fluid of choice?Fluid of choice?

The never ending crystalloid/colloid The never ending crystalloid/colloid debatedebate Insufficient evidence to suggest one Insufficient evidence to suggest one

over the otherover the other NB. Pentaspan and some other HES NB. Pentaspan and some other HES

associated with RF (and associated with RF (and coagulopathies) over maximum coagulopathies) over maximum suggested doses…controversialsuggested doses…controversial

Will this be fixed with voluven?Will this be fixed with voluven?

What about optimizing What about optimizing renal perfusion?renal perfusion?

Renal perfusion autoregulates between MAP Renal perfusion autoregulates between MAP 80-160 mmHg to maintain stable GFR80-160 mmHg to maintain stable GFR Unclear what ideal MAP is to “protect” kidneysUnclear what ideal MAP is to “protect” kidneys In septic shock, 85 was NOT better than 65In septic shock, 85 was NOT better than 65 One study used doppler U/S to assess renal One study used doppler U/S to assess renal

resistive indices to individualize MAP goalsresistive indices to individualize MAP goals Taking MAP from 65-75 mmHg led to increased UO an Taking MAP from 65-75 mmHg led to increased UO an

decreased resistancedecreased resistance No improvement when MAP from 75-85 mmHgNo improvement when MAP from 75-85 mmHg

Perfusion IssuesPerfusion Issues

What is the optimal perfusion pressure What is the optimal perfusion pressure in people with chronic HTN? RAS?in people with chronic HTN? RAS?

What to do with BP Meds:What to do with BP Meds: HCTZ… addressed earlierHCTZ… addressed earlier ACE/ARB/DRI…ACE/ARB/DRI…

Alters renal regulationAlters renal regulation Associated with post-induction hypotensionAssociated with post-induction hypotension No clear renal outcome data periopNo clear renal outcome data periop Individualize periop RAAS agent managementIndividualize periop RAAS agent management

What about the What about the Surgeons?Surgeons?

Cardiac Surgery (yes again…)Cardiac Surgery (yes again…) Duration of pump runDuration of pump run

Risk increases over 100 minutesRisk 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 More data to come from long term analysis of continuous flow HeartMate 2 VADScontinuous flow HeartMate 2 VADS

What about the role of Off-pump bypassWhat about the role of Off-pump bypass Lower incidence of AKI (and other CPB Lower incidence of AKI (and other CPB

complications)complications) But…recent concerns about cardiac outcomes But…recent concerns about cardiac outcomes

Blame the SurgeonsBlame the Surgeons

AAAAAA Related to duration of cross-clampRelated to duration of cross-clamp Can be technical as well if they “bag” Can be technical as well if they “bag”

the renalsthe renals Suggestion of improved outcomes with Suggestion of improved outcomes with

endovascular repairsendovascular repairs Thus to be considered when risk stratifying Thus to be considered when risk stratifying

preoperativelypreoperatively

Can we blame general Can we blame general surgeons too?surgeons too?

LaparoscopyLaparoscopy Renal blood flow and function are reduced Renal blood flow and function are reduced

during pneumoperitoneum during pneumoperitoneum As intrabdominal pressure increases, U/O As intrabdominal pressure increases, U/O

decreases….decreases…. Form of abdominal compartment syndromeForm of abdominal compartment syndrome Likely safe under 15 Likely safe under 15

Case reports of renal failure post-laparoscopy Case reports of renal failure post-laparoscopy existexist

? Role of hypovolemia as contributor? Role of hypovolemia as contributor Can consider gasless laparoscopy in those at Can consider gasless laparoscopy in those at

high risk!!! high risk!!! ?RAS?RAS

Yet another hit on Yet another hit on transfusiontransfusion

Independently Independently associated with associated with increased risk of increased risk of post-op AKI in OLT post-op AKI in OLT patients.patients.

As always…As always… ? Cause/effect? Cause/effect

So now what?So now what?

If we identify If we identify patients at risk…patients at risk…

And mitigate all And mitigate all that is that is controllable…controllable…

Is there any Is there any targeted therapies targeted therapies we can try to we can try to decrease the risk decrease the risk of periop RF?of periop RF?

Good old fashioned LasixGood old fashioned Lasix ““inhibition of renal tubular inhibition of renal tubular

oxygen consumption”oxygen consumption” Animal models…?mechanismAnimal models…?mechanism

Would it prevent ischemia Would it prevent ischemia during times of low delivery?during times of low delivery? Like cross clamping!Like cross clamping!

Has Has NOT NOT been shown to been shown to decrease perioperative AKIdecrease perioperative AKI

Will increase urine output, Will increase urine output, convert to non-oliguric, which convert to non-oliguric, which may be usefulmay be useful But no change in hard endpointsBut no change in hard endpoints

““Renal Dose” DopamineRenal Dose” Dopamine

Has been Has been extensively extensively studied…studied…

Will increase urine Will increase urine output; which may output; which may not be a bad thingnot be a bad thing

Has numerous side Has numerous side effectseffects

Does NOT protect Does NOT protect patients from AKIpatients from AKI

What if we’re NOT afraid of What if we’re NOT afraid of the Gamcaththe Gamcath??

Prophylactic DialysisProphylactic Dialysis Has been evaluated in extremely high Has been evaluated in extremely high

risk surgeries; case controlrisk surgeries; case control OLT in patients with borderline renal OLT in patients with borderline renal

function preopfunction preop Did not decrease rates of Did not decrease rates of

perioperative AKIperioperative AKI But useful to manage complications like But useful to manage complications like

hypervolemia, acidosis and hyperkalemiahypervolemia, acidosis and hyperkalemia

Is there any hope?Is there any hope?

Fenoldopam!!!Fenoldopam!!!

Dopamine-I receptor agonist Dopamine-I receptor agonist approved for the treatment of approved for the treatment of hypertensive emergencieshypertensive emergencies

BackgroundBackground Selective short-acting Dopamine-1 agonistSelective short-acting Dopamine-1 agonist

Smooth-muscle relaxationSmooth-muscle relaxation Renal vasodilatationRenal vasodilatation Tubular sodium reabsorptionTubular sodium reabsorption

Data existing is all over the mapData existing is all over the map Previous large study was negative, but control Previous large study was negative, but control

group was dopamine! Also used lower dose.group was dopamine! Also used lower dose. Aim is confirm effectiveness of fenoldopam Aim is confirm effectiveness of fenoldopam

0.1 0.1 g/kg/min for preserving RF in g/kg/min for preserving RF in patients undergoing elective heart surgery patients undergoing elective heart surgery who are at high risk for postop AKIwho are at high risk for postop AKI

MethodsMethods

Inclusion Criteria:Inclusion Criteria: ONE of the following RF (and elective heart ONE of the following RF (and elective heart

surgery)surgery) Creat >1.5 mg/dl (132 Creat >1.5 mg/dl (132 mol/L)mol/L) Age >70Age >70 DM on insulinDM on insulin Repeat sternotomyRepeat sternotomy

Exclusion Criteria:Exclusion Criteria: <18 y/o<18 y/o Preop dialysis or inotropesPreop dialysis or inotropes Allergy to fenoldopamAllergy to fenoldopam

MethodsMethods Usual cardiac surgery technique was usedUsual cardiac surgery technique was used No aprotinin givenNo aprotinin given Standard criteria to give vasopressors, Standard criteria to give vasopressors,

fluid and inotropes definedfluid and inotropes defined Computer generated randomization to Computer generated randomization to

fenoldopam vs placebo, investigators, fenoldopam vs placebo, investigators, clinicians and patients blinded to clinicians and patients blinded to assignment.assignment.

Primary Endpoint:Primary Endpoint: AKI, post-op creat > AKI, post-op creat > 2 mg/dl (177 2 mg/dl (177 mol/L) on day 1 or 2mol/L) on day 1 or 2

ResultsResults

ResultsResults

ResultsResults

CRRT started in 0/95 patients in the fenoldopam CRRT started in 0/95 patients in the fenoldopam group, compared to 8/98 (8.2%) in placebogroup, 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?

Other stuff?Other stuff?

AnaritideAnaritide recombinant human atrial natriuretic peptide, recombinant human atrial natriuretic peptide, an infusion of 50 ng/kg/min decreased the an infusion of 50 ng/kg/min decreased the

probability of dialysis in a study of postcardiac probability of dialysis in a study of postcardiac surgical surgical heart failureheart failure patients with AKI. patients with AKI.

Take Home MessagesTake Home Messages

Periop AKI is common and seriousPeriop AKI is common and serious Judicious management of volume Judicious management of volume

and pressure is importantand pressure is important Be aware of high risk patients and Be aware of high risk patients and

try to avoid doing silly things to try to avoid doing silly things to themthem

Await further studies on Fenoldopam Await further studies on Fenoldopam and anaritide.and anaritide.

Questions?Questions?

ReferencesReferences Zanardo G, Michielon P, Paccagnella A, et al. Acute renal failure in the patient 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 undergoing cardiac operation. Prevalence, mortality rate, and main risk factors. J Thorac Cardiovasc Surg. 1994;107:1489–1495.Cardiovasc Surg. 1994;107:1489–1495.

Thakar CV, Arrigain S, Worley S, et al. A clinical score to predict acute renal failure after 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.cardiac surgery. J Am Soc Nephrol. 2005;16:162–168.

Kheterpal S, Tremper KK, Englesbe MJ, et al. Predictors of postoperative acute renal Kheterpal S, Tremper KK, Englesbe MJ, et al. Predictors of postoperative acute renal failure after noncardiac surgery in patients with previously normal renal function. failure after noncardiac surgery in patients with previously normal renal function. Anesthesiology. 2007;107:892–902.Anesthesiology. 2007;107:892–902.

Thakar CV, Kharat V, Blanck S, et al. Acute kidney injury after gastric bypass surgery. Thakar CV, Kharat V, Blanck S, et al. Acute kidney injury after gastric bypass surgery. Clin J Am Soc Nephrol. 2007;2:426–430.Clin J Am Soc Nephrol. 2007;2:426–430.

Barratt J, Parajasingam R, Sayers RD, et al. Outcome of acute renal failure following 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. surgical repair of ruptured abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2000;20:163–168.2000;20:163–168.

Sward K, Valsson F, Odencrants P et al. Recombinant human atrial natriuretic peptide in 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 ischemic acute renal failure: a randomized placebo-controlled trial. Critical Care Medicine 2004 Jun; 32(6): 1310–1315.2004 Jun; 32(6): 1310–1315.

Kellum JA & Decker M. Use of dopamine in acute renal failure: a meta-analysis. Critical Kellum JA & Decker M. Use of dopamine in acute renal failure: a meta-analysis. Critical Care Medicin 2001 Aug; 29(8): 1526–1531Care Medicin 2001 Aug; 29(8): 1526–1531

Deruddre S, Cheisson G, Mazoit JX et al. Renal arterial resistance in septic shock: effects 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 of increasing mean arterial pressure with norepinephrine on the renal resistive index assessed with Doppler ultrasonography. Intensive Care Medicine 2007 May 8assessed with Doppler ultrasonography. Intensive Care Medicine 2007 May 8