Perioperative Renal Failure: Can
we avoid the Gamcath?
Blair Schwartz
January 26th, 2010
Objectives
1.
2.
3.
Review pathophysiology and diagnostic criteria
for perioperative renal failure
Review risk factors for the development of
perioperative renal failure
Discuss potential methods for preventing
perioperative renal failure and thus avoid the
dreaded (by some) Gamcath.
The definition conundrum



The major problem in
“acute renal failure”
research is one of lack of
clear definition
Over 35 different definitions
exist in the literature
Thus getting a handle on the
problem is difficult
Solving things the Charlton Heston
way…
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).”

Must be in the context of adequate hydration
The new RIFLE Criteria
RRT is automatically stage 3
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.
Problems with the criteria?

Urine output not solely a reflection of renal function


Volume status
Serum Creatinine is often slow to respond and thus not
an ideal marker
Future fixes…

Neutrophil GelatinaseAssoc. Lipocalin (NGAL)


Cystatin C



Levels in blood and urine
rise within a few hours after
injury
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
Prevalence of perioperative RF

Multitude of definitions makes determining the
prevalence of RF very difficult

Cardiac Surgery



Gastric Bypass


GFR < 50 ml/min 0.8%
AAA


AKI 8.5%
Non-Cardiac Surgery


AKI 7.7-11.4%
CRRT <1 -5%
AKI 15-46%
OLT


AKI 48-94%
CRRT 8-17%
Prevalence unclear, importance
settled.

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
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%
Similar numbers for OLT and AAA
Cardiac Surgery:



Mortality rate 0.8% without renal dysfunction
9.5% with AKI
44.4% with renal failure and RRT need
So…




Periop RF is common
Periop RF is associated
with poor outcome
Associated temporally
with an identifiable event
In theory…. Perhaps a
target for prevention!!!
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?
Assuming we can intervene…

Can analyze risk factors:



Preoperative factors
Intraoperative factors
Postoperative factors
Preoperative Risk Factors

Kheterpal
15,000 patients with normal preoperative RF
undergoing non-cardiac surgery
 identified the following independent risk factors for
post-op RF:

Age
 Emergency Surgery
 BMI > 33
 Peripheral Vascular Occlusive Disease
 COPD needing bronchodilator therapy

Always with the hearts
Summary…

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
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
More preop things…

“Maintenance of adequate intravascular
volume”
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
 Thus an important part of the perioperative
consultation


Particularly in emergent surgery, and definitely in hip
fractures!!!!
Volume et al…

Unclear what the best way to determine this is…
History
 Physical exam
 Swann?


All methods have their limitations, thus likely a
combination of some/all of the above
Peri-operative Issues




Examine for volume status
Be cognizant of NPO duration, frequent cancellations
and ensure adequate maintenance fluids
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

Keep a keen eye as well for all other nephrotoxins
Fluid of choice?

The never ending crystalloid/colloid debate
Insufficient evidence to suggest one over the other
 NB. Pentaspan and some other HES associated with
RF (and coagulopathies) over maximum suggested
doses…controversial
 Will this be fixed with voluven?

What about optimizing renal
perfusion?

Renal perfusion autoregulates between MAP 80160 mmHg to maintain stable GFR
Unclear what ideal MAP is to “protect” kidneys
 In septic shock, 85 was NOT better than 65
 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
 No improvement when MAP from 75-85 mmHg

Perfusion Issues


What is the optimal perfusion pressure in people
with chronic HTN? RAS?
What to do with BP Meds:
HCTZ… addressed earlier
 ACE/ARB/DRI…

Alters renal regulation
 Associated with post-induction hypotension
 No clear renal outcome data periop
 Individualize periop RAAS agent management

What about the Surgeons?

Cardiac Surgery (yes again…)

Duration of pump run


? Lack of pulsatile flow as aetiology


Risk increases over 100 minutes
More data to come from long term analysis of continuous
flow HeartMate 2 VADS
What about the role of Off-pump bypass
Lower incidence of AKI (and other CPB complications)
 But…recent concerns about cardiac outcomes

Blame the Surgeons

AAA
Related to duration of cross-clamp
 Can be technical as well if they “bag” the renals
 Suggestion of improved outcomes with
endovascular repairs


Thus to be considered when risk stratifying preoperatively
Can we blame general surgeons too?

Laparoscopy


Renal blood flow and function are reduced during
pneumoperitoneum
As intrabdominal pressure increases, U/O decreases….





Form of abdominal compartment syndrome
Likely safe under 15
Case reports of renal failure post-laparoscopy exist
? Role of hypovolemia as contributor
Can consider gasless laparoscopy in those at high risk!!!

?RAS
Yet another hit on transfusion


Independently associated
with increased risk of
post-op AKI in OLT
patients.
As always…

? Cause/effect
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?
Good old fashioned Lasix

“inhibition of renal tubular oxygen
consumption”


Would it prevent ischemia during times
of low delivery?



Animal models…?mechanism
Like cross clamping!
Has NOT been shown to decrease
perioperative AKI
Will increase urine output, convert to
non-oliguric, which may be useful

But no change in hard endpoints
“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
What if we’re NOT afraid of the
Gamcath?


Prophylactic Dialysis
Has been evaluated in extremely high risk
surgeries; case control


OLT in patients with borderline renal function preop
Did not decrease rates of perioperative AKI

But useful to manage complications like
hypervolemia, acidosis and hyperkalemia
Is there any hope?
Fenoldopam!!!

Dopamine-I receptor agonist approved for the
treatment of hypertensive emergencies
Background

Selective short-acting Dopamine-1 agonist




Data existing is all over the map


Smooth-muscle relaxation
Renal vasodilatation
Tubular sodium reabsorption
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
Methods

Inclusion Criteria:

ONE of the following RF (and elective heart surgery)





Creat >1.5 mg/dl (132 mol/L)
Age >70
DM on insulin
Repeat sternotomy
Exclusion Criteria:



<18 y/o
Preop dialysis or inotropes
Allergy to fenoldopam
Methods





Usual cardiac surgery technique was used
No aprotinin given
Standard criteria to give vasopressors, fluid and
inotropes defined
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
Results
Results
Results

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?
Other stuff ?

Anaritide


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.
Take Home Messages




Periop AKI is common and serious
Judicious management of volume and pressure
is important
Be aware of high risk patients and try to avoid
doing silly things to them
Await further studies on Fenoldopam and
anaritide.
Questions?
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.
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.
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.
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
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