murray casestudiesinnephrology

8/10/2019 Murray CaseStudiesInNephrology

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Case Studies in NephrologySHM 2005

Patrick Murray, M.D.

Associate Professor of Medicine,Anesthesia & Critical Care, and Clinical

Pharmacology

University of Chicago

[email protected]


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Outline

Acute Renal Failure (ARF) Prevention

Renal Function Monitoring

Diagnostic Approach to ARF

Medical Management of ARF Acute Renal Replacement Therapy (RRT)


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Acute Renal/Kidney Failure

A rapid decrement in renalfunction, occurring over days to

weeks, resulting in accumulation ofnitrogenous wastes (azotemia)


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Case #1: Radiocontrast Nephropathy?


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Case Presentation

66 yo AA female with 5 month history of low back pain,admitted for tumor embolization

Nephrology consultation requested regarding increasedcreatinine

HPI: PMHx notable only for glaucoma. Meds: Vicodin, Elavil, occ. Advil

Developed LBP 5 months prior to admission, assoc. with weight loss and

fatigue Infused CT of abdomen/pelvis 2 months PTA revealed a destructive soft

tissue mass with bone erosion at L-1, with extension through the rightforamen in dumbbell fashion

MRI, LSS plain films were confirmatory CT-guided bx 2 months PTA: malignant hemangiopericytoma

Negative infused chest and head CT scans 1 month PTA

Admitted for preoperative tumor embolization and resection: received

100-150ml nonionic, low osmolar dye prior to admission


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Malignant Hemangiopericytoma


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Malignant Hemangiopericytoma


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Examination 70kg woman Temp 36.9

P 92 reg BP 158/80

UOP ~30ml/hour IVF D5.45 60ml/hour HEENT: unremarkable, JVD 5-6 cm H2O

Cor- 2/6 pansystolic murmur LLSB, no gallop

Lungs- clear Abdomen- soft, NT, ND, no masses or organomegaly. Foley

catheter

Extremities: warm, brisk capillary refill, minimal edema Back- minimal lumbar tenderness

Neurologically intact


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Laboratory Data

Na 137 / K 4.8 / Cl 97 / HCO3 24 / BUN 48 / Cr 4.5

Glucose 120 / AG 16 / Ca 9.6 / PO4 5 / Mg 1.9

WBC 6.1 / Hb 6.2 (NC, NC) / Hct 18.2 / Plts 120K

PTT 20 / INR 0.9 / Albumin 4.4 / LFTs wnl

Urinalysis: Dipstick- SpG 1.016, 1+ protein, 1+ heme, o/w negative

Microscopy- occ. RBC, occ. granular casts, no crystals

U/S: normal kidney sizes (11.4cm), slight increased

echogenicity, no hydronephrosis

CXR: clear


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Renal Function Trend

101-150CT scan271.22

101-150Embolization484.50

101-150CT scan3821

N/AN/A210.98

Radiocontrast

volume(nonionic,

ml)

ProcedureBUN

(mg/dl)

Serum

Creatinine(mg/dl)

Date (Months

Prior ToAdmission)

Estimated GFR = 13 ml/min/1.73m2


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Hematocrit Levels Fall asKidney Function Declines

Adapted from Radtke et al. Blood. 1979;54:877-884.

* 25%-40% of kidney function. 10%-15% of kidney function.

91 40-90 30-39 20-29 10-19

10

CCr (mL/min/1.73 m2)

0

10

20

30

40

50

MeanHc

t(vol%)

n=18n=59 n=18 n=34 n=18n=29

*


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Initial Hospital Course

Volume expansion: NS 150ml/hour

Serum creatinine trend: increased by maximum of 0.3mg/dl

within 72 hours

24 hour urine: 3.86 grams proteinuria, creatinine clearance

13ml/minute

Peripheral smear: numerous atypical plasma cells noted SPEP: TP 7.1 g/dl, 0.1g/dl monoclonal kappa light chain spike

UIEP: 3.94 grams/24 hour proteinuria, with monoclonal free

kappa lights chains accounting for 44% of urine protein Skeletal survey: lytic lesions in skull, vertebrae (T10, T12, L1),

right femur, bilateral tibias


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Light Chain Immunostaining

KAPPA LAMBDA


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Subsequent Course

Tumor pathology:

Original stains for keratins, synaptophysins, and lymphoid

differentiation negative Additional immunohistochemical stains positive for kappa

light chains, negative lambda = Plasmacytoma

BMBx: Markedly hypercellular, 85% plasma cells, 10-20% immature

Rx with XRT, melphalan, and dexamethasone Developed ESRD and initiated HD 1.5 years later

Expired 2.5 years after diagnosis


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Renal Manifestations of Multiple Myeloma Renal tubular acidosis

Proximal, with Fanconi syndrome

Myeloma kidney

Presents with ARF or CRI

Tubular injury and Cast Nephropathy (obstruction)

Amyloidosis (primary, AL) and Light Chain Deposition Disease

Whole light chains (LDDD) or Light chain fragments (amyloid)deposited; typical presentation is nephrotic syndrome

Hypercalcemia

Uric acid nephropathy Plasma cell renal infiltration

Drug-induced ARF: hypovolemia + radiocontrast, NSAIDs,ACE inhibitors


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Myeloma & Radiocontrast Nephropathy

Myeloma reportedly predisposes to radiocontrastnephropathy

McCarthy CS, et al: Radiology 1992;183:519 Volume depletion promotes intratubular light chain

precipitation to form casts

Exacerbated by hypercalcemia Smolens P, et al: J Lab Clin Med 1987;110:460

? Charge interaction between light chains and

radiocontrast promoting precipitation Worse with ionic dyes, acid urine

Holland MD, et al: Kidney International 1985;27:46


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Radiocontrast Nephropathy (RCN)

Definition: acute decrement in renal function followingradiocontrast administration

Usually defined as serum creatinine increase of 0.5mg/dl or

25% within 48 (-96) hours of dye

3rd commonest cause of hospital-acquired ARF

Usually acute-on-chronic renal failure, superimposedon CKD (not normal renal function)

Typically, serum creatinine increases within 24-48

hours, reaches peak and plateau in 3-5 days, decreases Increases morbidity, cost, and mortality

Adjusted odds ratio 5.5 for in-hospital mortality (vs no RCN)

Levy EM, et al: JAMA 1996;275:1489-94


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Mortality Rates for Patients with

Radiocontrast Nephropathy

McCullough et.al Am. J. Med. 1997


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Pathogenesis of RCN

Oxidant Injury

Hyperosmolar contrast triggers generation ofreactive oxygen species

Other Cytotoxic effects

Renal vasoconstriction Aggravating in medullary hypoxia

Intratubular precipitation of dye crystals


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PaO2

10-20

PaO2+ 50

Blood Flow and Interstitial O2 Content: Regional

Distribution in Cortex/Medulla

1.9 ml/gm/min

4.2 ml/

gm/min

Brezis M, Rosen S: N Engl J Med 1995;332:647-655


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Mechanism


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RCN Risk Factors

Confirmed Suspected

Serum Cr > 1.5 mg/dl

Diabetic Nephropathy

Class III/IV NYHC CHF

Multiple Myeloma

Volume contrast media

Repeat dye < 48 hours

Hypertension

Abnormal LFT

Age

Gender

Concomitant useloop diuretics

Porter G.A. Invest. Rad. 1993


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RCN risk after Primary PCI in AMI

Marenzi G, et al: JACC 2004;44:1780-5

Variables (Odds Ratio):

Age 75 (5.28)

Anterior MI (2.17)

Time-to-reperfusion 6h (2.5)

Contrast 300ml (2.8)

IABP (15.51)


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RCN IncidenceStudy No. Patients Entry Cr Incidence

Fenoldopam 1999 50 2.61 29.0%

Multicenter trial

P.R.I.N.C.E. 1999 98 2.46 36.7%

Endothelin Receptor 158 2.76 29.0%

Antagonist Trial 1999

ANP Multicenter Trial 247 1.5-1.8 19.0%

1998

Iohexol Cooperative 1196/509 1.5 11.6%

Study 1995

Solomon 1993 78 2.1 11.0%

Harvard University


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Incidence Doubles In Patients With Diabetic

Nephropathy

27 %2 4

81 %> 4

3.6 %< 2

IncidencePre-ProcedureCreatinine Level

Berns AS.Kidney Int. 1989


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Radiocontrast Nephropathy Prevention:

General Measures Estimate GFR

ARF: ? reversible

CRI: stratify risk, counselling, prophylaxis Consider alternatives

Eg. MRA with gadolinium contrast

Adjust Medications Stop NSAIDs

Hold diuretics

Consider holding ACE inhibitors or ARBs if for HTN, CKD, not CHF?(opinion)

Hold metformin

Radiocontrast selection Smallest volume of nonionic, isoosmolar dye preferred for high risk

patients


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Clarifying the Nomenclature

120180 75 55 25 15 5

GFR (mL/min/1.73 m2)

Disease

Severity

AtAt

riskrisk

CKD Continuum

ESRDESRDCRICRI

United States Renal Database System. 2000 Atlas of ESRD in the United States.


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The Incidence of ESRD Is

Increasing

United States Renal Database System. 2000 Atlas of ESRD in the United States.

Greatest Increase Seen in Diabetic ESRD

0

20,000

40,000

60,000

80,000

100,000

1989 1990 1991 1992 1993 1994 1995 1996 1997 1998

All ESRD

Diabetes

Hypertension

Glomerulonephritis

InIncidenceofNew

Patien

ts


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Estimates of CRI in the United States

Based on NHANES III Data

Jones et al.Am J Kidney Dis. 1998;32:992-999 (published correction inAm J Kidney Dis.

2000;35:178). United States Renal Database System. 2000 Atlas of ESRD in the United States.

Unknown

0.26

0.8

2.5

6.2

RRT

SCr 2.0 mg/dL

SCr

1.7 mg/dL

SCr 1.5 mg/dL

SCr

1.4 mg/dL

Millions of individuals


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JNC VII: CKD is a Major CV Risk Factor

Major Risk Factors include: Estimated GFR


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Detection and Management Issues

in Patients at RiskGFR

Serum creatinine

BUN

Creatinine clearance

measured calculated (CG)

GFR

measured

calculated (MDRD)

BUN = blood urea nitrogen; CG = Cockcroft-Gault; GFR = glomerular filtration rate; MDRD = Modification of

Diet in Renal Disease Study; Ca/PO4 = calcium and phosphate; iPTH = intact parathyroid hormone.

Kidney Damage

Microalbuminuria

Clinical proteinuria

Metabolic Aspects

Hemoglobin/hematocrit

Total cholesterol

Triglycerides

Ca/PO4

iPTH

Serum bicarbonate

Serum electrolytes


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Plasma Creatinine

Directly proportional to muscle mass (Kasiske & Keane, 1999)

Inversely proportional to GFR

Equations relating age, sex, race, size (muscle mass) to plasma

creatinine to estimate GFR all depend on steady-state conditions

If serum creatinine and GFR are unstable, these equations

(Cockroft-Gault, MDRD) are invalid

Serial plasma creatinine elevations of 0.5-1mg/dl/day signify the

absence of significant GFR (Moran SM, et al: Kidney Int 1985)

Creatinine clearance (24-hour collection) overestimates GFRbecause of tubular secretion, increasingly inaccurate with

declining GFR in chronic glomerular disease (Shemesh O, et al:

Kidney International 1985;28:830-838)


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CreatinineExcretion(m

g/d)

2000

1600

1200

800

400

0

Men (n=149) Women (n=219)

Creatinine

Excretion(mg/kg

/d)

25

20

15

10

5

0

Men (n=149) Women (n=219)

Age (y) Age (y)

| | | | | | | |

25 35 45 55 65 75 85 95| | | | | | | |

25 35 45 55 65 75 85 95

| | | | | | | | | | | | | | | |

Kasiske &Keane,

In: Brenner

& Rector,

1996

24 hour Creatinine

Excretion (mg/day)

24 hour Creatinine

Excretion (mg/kg)

Relationship of

Age andSex to Creatinine

Excretion


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20

16

8.0

4.0

2.0 1.0

SERUM

CRE

ATININE

(mg

/dL)

NEPHRON LOSS62,500 125,000

LOSS OF250,000 NEPHRONS

| | | | | | |

50 100

LOSS OF 500,000 NEPHRONS LOSS OF 1,000,000 NEPHRONS

1.5

6

3.1

35

6.2

5

12.5 2

5

Rudnick, et al, In: Brenner & Lazarus, 1988

Serum

Creatinine

(mg%)

Non-Linear SCr-GFR relationship in CKD


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Creatinine Clearance versus GFR (inulin CL)

in Chronic Glomerular Disease

Shemesh O, et al: Kidney International 1985;28:830-838


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GFR,mL/min per 1.73 m2

| | | | | | | |

0 30 60 90 120 150 180 210

210

180

150

120

90

60

30

0

21

18

15

12

9

6

3

A

GFR,mL/min per 1.73 m2

| | | | | | | |

0 30 60 90 120 150 180 210

210

180

150

120

90

60

30

0

21

18

15

12

9

6

3

B

Levey, et al., Ann Int Med 1999;130:461-70

Creatinine CL (A) & Urea CL (B) vs. GFR

Creatinine CL (ml/min/1.73m2) Urea CL (ml/min/1.73m2)


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GFR, mL/min per 1.73 m2

| | | | | | | |

0 30 60 90 120 150 180 210

210

180

150

120

90

60

30

0

210

180

150

120

90

60

30

0

C


Mean of Creatinine CL & Urea CL vs GFR

Mean of Creatinine CL

& Urea CL (ml/min/1.73m2

)


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24-Hour Creatinine

Clearance210

180

150

120

90

60

30

00 30 60 90 120 150 180

Cr

eatinineClearance,mL/min/1.7

3m2

GFR, mL/min/1.73 m2 GFR, mL/min/1.73 m2

GFRPredictedbyUsingEq

uation7,

mL

/min/1.7

3m2

R2=86.6% R2=90.3%

No bias

Better precision

180

150

120

90

60

30

00 30 60 90 120 150 180

MDRD Study

Equation



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GFR Estimation

Abbreviated MDRD Study equation:GFR (ml/min/1.73m2) =

186 x (SCr)-1.154 x (Age)-0.203 x (0.742 iffemale) x (1.21if black)


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Stages of

Chronic Kidney DiseaseStage Description GFR

(mL/min/1.73 m2)

1 Kidney Damage withNormal or GFR

> 90

2 Kidney Damage with Mild

GFR60-89

3 Moderate GFR 30-59

4 Severe GFR 15-29

5 Kidney Failure


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Choice of Radiocontrast Agent

Sandler NEJM 2003;348:551

Na-Diatrizoate

Ionic Monomer

Iohexol

Nonionic Monomer

Nonionic Dimer

Iodixanol

1


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Types of Radiocontrast Agents

Iso-Osmolal

290

Low Osmolality

600-850

High Osmolality

1500- 1800

Osmolality

(mosm/kg)

Iohexol,

Iopamidol

Second Generation

Non-Ionic Monomers

IodixanolNewest Generation

Non-Ionic Dimers

Renografin, HypaqueFirst Generation

Ionic Monomers

ExamplesClass

Slide 42


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C1 Carmella Blankstein, 10/10/2004


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Nephrotoxicity in High-Risk Patients Study of Iso-Osmolar

and Low-Osmolar Non-Ionic Contrast Media

Aspelin P, et al: NEJM 2003; 348:491-499

Background: Prior investigations comparing iodixanol and

low-osmolar contrast in low-risk, nondiabetic patients foundno difference in incidence of CIN.

Design: Prospective, randomized, double-blind, multi-center

study to compare nephrotoxic effects of iohexol vs. iodixanol

in patients with diabetes undergoing coronary or aorto-

femoral angiography.

Inclusion: DM (type 1 or 2) and Cr 1.5-3.5 (M) and 1.3-3.5 (F)

Exclusion: Severe concomitant disease, HD, Renal Transplant


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Radiocontrast Nephropath Proph la is


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Radiocontrast Nephropathy Prophylaxis

Fluids

Diuretics

Vasodilators

Antioxidants Prophylactic renal replacement therapy

Comparative Efficacy of Saline Mannitol and


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R. Solomon, et al: NEJM 1994

Comparative Efficacy of Saline, Mannitol and

Furosemide in RCN Prophylaxis


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Mueller C, et al: Arch Int Med 162:329-36, 2002


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Oral vs Intravenous (0 45%) Pre Hydration


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Oral vs. Intravenous (0.45%) Pre-Hydration

36 patient RCT

Serum Creatinine 1.4mg/dl

(mean ~1.75mg/dl)

0.45% saline 75ml/hr for 12hrs pre-and post-cath vs.

outpatient 1liter clear liquids

po over 10hr pre- & 0.45%

saline 300ml/hr for 6hrs

during/after cath.

Max. creatinine 0.210.38

(inpatient) vs. 0.120.23(outpatient), p = NS

Taylor A, et al: Chest

1998;114:1570-74

O l I t (0 9%) P H d ti


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Oral vs. Intravenous (0.9%) Pre-Hydration

53 patient RCT

Serum creatinine ~1.2mg/dl

(80ml/min) Group 1 (0.9% saline 1ml/kg/hr

for 24hrs, beginning 12 hours

pre-cath) vs. Group 2(unrestricted oral fluids)

RCN rate:

Grp 1: 1/27 (3.7%) vs. Grp 2: 9/26(34.6%), p = 0.005

Trivedi H, et al: Nephron

2003;93:c29-c34

p = 0.02

p = 0.17

Prevention of Contrast - Induced Nephropathy


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p p y

With Sodium BicarbonateDesign:

A prospective, single-center, randomized trial in 119 patients

from 2002-2003.

Participants:

Patients with stable Cr 1.1mg/dl scheduled to

undergo either cardiac cath / IR procedure / CT

Intervention:

154 mEq/L of either NaCl or Bicarbonate. Bolus 3 mL/kg X 1 hr before iopamidol contrast then 1

mL/kg/hr during procedure and 6 hrs after.

Merten GJ, et al: JAMA 2004;291:2328-34



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p p y

With Sodium Bicarbonate




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Study Termination:

Midway through accumulation of patients, studyhalted because of ethical concern about continuingto expose the control group to the substantiallyhigher risk of contrast nephropathy.




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With Sodium Bicarbonateesults:


11.9 %(CI = 2.9 21.2)

1.7 %(1)

13.6 %(8)

Incidence ofnephropathy (No.of pts)

MeanDifference

BicarbonateNaCl(P = 0.02)



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Registry Phase:

191 patients with baseline Cr = 1.7mg/dl

Mean change in Cr = 0 % CIN in 3 of 191 patients. (1.6%)



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Leon I. Goldberg, M.D., Ph.D.

(1927-1989)


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Weisberg et.al., Renal Failure, 1993

(n = 15)

(n = 15)

Dopaminergic Agonists


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Dopamine

p g g


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Murphy MB et al: NEJM 2001; 345: 1548-56

Pilot Study of Fenoldopam Mesylate in Radiocontrast

N h h I id f RCN 48 H


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Nephropathy: Incidence of RCN at 48 Hours

Tumlin J, et al: AmHeart J 2002;143:894-

903

CONTRAST Trial: Algorithm


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315 patients at 28 U.S. centerscardiac procedures with calculated CrCl


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P=0.42P=0.42

P=0.54P=0.54P=0.27P=0.27

0.32

0.26

Mean Delta SCr

33.6% 30.1%

0%

10%

20%

30%

40%

50%

SCr increase

by > 25%

28.5%

24.0%

SCr increase

by > 50%

Stone GA, et al: JAMA 2003;290:2284-91

N-Acetylcysteine (NAC) Protocol


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N Acetylcysteine (NAC) ProtocolTepel M, et al: NEJM 343:180-4, 2000

Randomized

All received 0.45% saline 1ml/kg/hr 12 hours pre-

and post-contrast for CT

All received 75ml iopromide (Ultravist-300:nonionic, low osmolality)

Placebo-controlled

N-acetylcysteine 600mg po bid for two days,

before & after contrast.

Effects on Renal Function Tepel, NEJM 2000


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Variable Acet lc steine

(n=41)

Control

(n=42)

P Value

Baseline SCr

(mg/dl)2.5 1.3 2.4 1.3 0.55

48hr SCr (mg/dl)

-0.4 0.4 +0.2 0.6 < 0.001

ARF # (%) 1 (17) 9 (21) 0.01

Acetylcysteine for prevention of contrast


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nephropathy: meta-analysis

(Birck et al., Lancet 2003)

GFR-independent effects of NAC on Serum


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Creatinine Concentration

Hoffman U, et al: J Am Soc Nephrol 2004;15:407-410

Are there effects of NAC on serum creatinine that are

independent of GFR ?

Protocol: 50 healthy volunteers with normal renal function

administered NAC 600mg po bid

Serum Cystatin C used as alternate marker of GFR

Cystatin C is a 13 kDa basic protein; a cysteine protease inhibitor,

produced at a constant rate by nucleated cells

Completely cleared by unrestricted glomerular filtration, proximal

tubular reabsorption, and catabolism

Concentration independent of age, gender, and muscle mass.

GFR-independent effects of NAC on Serum


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Creatinine Concentration

Hoffman U, et al: J Am Soc Nephrol 2004;15:407-410

eGFR

Serum Creatinine

Serum Cystatin C


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Effect of NAC on CPK Activity

Molecular and Cellular Biochemistry 2000;210:23-28

Prophylactic Hemodialysis


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Simultaneous HD: 17 patients with SCr3mg/dl

undergoing coronary angiography

RCT, 4 hours HD (+ saline) vs.control (saline alone)

Radiocontrast clearance augmented

in HD grp (n = 7) vs control (n =

10)

No effect on creatinine clearance at

1 and 8 weeks, c/w baseline

2 patients per group started HD in8 weeks

Frank H, et al: Clin Nephrol

2003;60:176Vogt et al: Am J Med 2001;111:692

Post-contrast HD:ARF 16 vs 24%; Week 1 HD 5 vs 15%

HD grp; n = 44

Non-HD grp; n = 50

Non-HD grp; n = 25

HD grp; n = 24

Hemofiltration AccessAccess


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HemofiltrationHemofiltration

CVVHCVVH

ContinuousContinuous

VenoVeno--VenousVenous


ReturnReturn

ReplacementReplacement

EffluentEffluent

The Prevention of Radiocontrast-Agent-Induced


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Nephropathy by Hemofiltration

Participants: 114 patients with CRI scheduled to

undergo coronary angiography or elective PCI.

Inclusion: Cr 2 or CrCl 50

Exclusion: ACS, Cardiogenic shock, Overt

CHF, Chronic Dialysis.

Marenzi G, et al: NEJM 2003;349:1333-40



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Nephropathy by HemofiltrationStudy Desing:

HemofiltrationHemofiltrationHemofiltration

RandomizeRandomize

IV HydrationIV HydrationIV Hydration

Setting: ICU

CVVH via Femoral Vein

Start: 4-6 hrs pre procedure

Finish: 18-24 hrs post procedure

Used isotonic replacementfluid at rate of 1000 ml / hour with an

equal ultrafiltrate rate

Heparin 5,000 U bolus

Setting: Step-down unit

IV Normal Saline @ 1mL/kg/hr

Start: 6-8 hrs pre procedure

Finish: 24 hrs post procedure




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Nephropathy by Hemofiltration

Marenzi G, et al: NEJ

2003;349:1333-40



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Nephropathy by Hemofiltrationesults:

30%10%One year

mortality

(p=0.01)

14%2%

In-hospital

mortallity

(p=0.02)

25%3%RRT

50%5%CIN

(p


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Nephropathy by HemofiltrationLimitations:

Flawed primary endpoint: HF lowers serum creatinine

independent of native renal function, radiocontrast effect

Different level of care for each group

ICU vs. floor

Heparin vs. No Heparin

Mechanism of benefit unclear: ? bicarbonate

High cost


Radiocontrast Nephropathy Prevention


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Estimate GFR ARF: ? reversible CRI: stratify risk, counselling, prophylaxis

Consider alternatives Eg. MRA with gadolinium contrast

Adjust Medications Stop NSAIDs

Hold diuretics

Consider holding ACE inhibitors or ARBs if for HTN, CKD, not CHF? (opinion)

Hold metformin

Radiocontrast selection Smallest volume of nonionic, isoosmolar dye preferred for high risk patients

Volume expansion Normal saline 1ml/kg/hour for 12 hours before and 12 hours after dye

Oral volume expansion prior if same-day/outpatient

Sodium bicarbonate 150mEq/l is preferred same-day therapy: 3ml/kg over 1 hour, then1ml/kg/hr during and for 6 hours after procedure [CAVEAT: hypokalemia]

Consider N-acetyl cysteine (600mg po bid pre- and post-dye; IV option also)

No proven role for prophylactic renal replacement therapy, vasodilators


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Case #2: Does this Patient Need Dialysis?

Case Presentation #2


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43 yo white female, transferred from a communityhospital following 2 week hospitalization withbacteremic pneumococcal pneumonia, progressing toseptic shock, ARDS, acute hypoxemic respiratory

failure Previously healthy, no medications apart from oral

contraceptive, family history of fatal post-partum TTP

in sister Right ventricular mass noted on echocardiogram,

systemic heparin initiated, transferred to UofC for

further evaluation and surgery Helical CT and repeat echo obtained

Renal Consult for oliguric ARF

Examination


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70kg woman Temp 36.9 P 102 ST BP 100/60, on NE infusion

CVP 22 ScvO2 70%

UOP 10ml/hour IVF 40ml/hour Lasix 20mg/hour

Vent: A/C 60% O2, 10 PEEP, VT 400ml, RR 36, Ppeak 39,Pplat 20

ABG 7.39 / 52 / 62 / 31, 91% Extremities: warm, brisk capillary refill, minimal edema

Cor- loud P2; Lungs- bilateral rales; no other remarkable

findings CXR: bilateral diffuse alveolar infiltrates

CT: multiple pulmonary emboli, diffuse consolidation


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How bad is the renal dysfunction?

Urine output: what is adequate?......


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..to maintain Fluid balance? Oliguria may be appropriate in patients with hypovolemia

and prerenal azotemia

Adequate volume expansion reverses oliguria Oliguria is maladaptive in patients with congestive heartfailure, cirrhosis, and acute tubular necrosis

Positive fluid balance causes volume overload

Diuretics dont increase renal blood flow, GFR, or non-electrolyte solute excretion

Only electrolytes and associated water are excreted in the

extra urine output (UOP) Diuretics can prevent volume overload in ARF, but notnitrogenous waste accumulation (azotemia), and may beassociated with worse outcome (Mehta, JAMA Nov 2002)

Urine output: what is adequate?......

i i S l E i ?


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..to maintain Solute Excretion? Traditional oliguria definition of 400ml/day assumes

maximal urine concentrating ability (1200mOsm/kg), and

solute production of 480mOsm/day (6mOsm/kg, in an 80kgpatient)

This corresponds to UOP of only 16ml/hour ( 0.2ml/kg/hour)

This UOP is clearly inadequate to maintain fluid balance inthe face of large obligate intakes in ICU patients

This UOP is also inadequate for solute clearance in thosewith submaximal urinary concentrating ability (age, renaldisease), increased solute production/appearance(hypercatabolism, parenteral nutrition), or both

RIFLE Criteria for Acute Renal DysfunctionGFR Criteria* Urine Output Criteria


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Risk

Injury

Failure

Loss

ESRD

Increase creat x1.5 or GFR

decrease > 25%

End Stage Renal Disease * *

UO < .3ml/kg/hx 24 hr or

Anuria x 12 hrs

UO < .5ml/kg/h

x 12 hr

UO < .5ml/kg/h

x 6 hr

Increase creat x2or GFR decrease

>50%

Increase creat x3or GFR decrease

> 75%

High

Sensitivity

High

Specificity

Persistent ARF = RRT > 4 weeks* Abrupt (1-7 days)Sustained (>24 hrs)

** RRT > 3months

www.ADQI.netKellum JA, et al: Curr Opin in Crit Care 2003;8:509-14

GFR assessment

E ti ti b k


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Estimation by serum markers

Plasma creatinine

Plasma urea nitrogen

Plasma cystatin C

Estimation by clearance measurements

Endogenous markers Creatinine clearance, Urea clearance, Combination techniques

Exogenous markers

Aminoglycoside clearance (clinical use)

Hot radionuclides

Cold radiocontrast agents

120

100

80l/

min

Surgery, MI, sepsisMoran SM, Myers BD: Kidney International1985;27:928-37

GFR

(ml/min)


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Time, days

80

60

40

20

0 7

6

5

4

3

2

1

0

GFR,

ml/

C

rea

tin

ine

,

mg

%

Reversal of ischemia

| | | | |

0 7 14 21 28

(ml/min)

Serum

Creatinine

(mg%)

Abbreviated Creatinine Clearance

G d l ti ( 0 95) b t 2 h d 22


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Good correlation (r = 0.95) between 2-hour and 22-hour creatinine clearance in ICU patients

Sladen RN, et al: Anesthesiology 1987;67:1013-6

Good correlation between repeated 2-hour creatinine

clearances in ICU patients

Mean difference 0.8ml/min Herget-Rosenthal S, et al: Clin Nephrol 1999;51:348-54

Acute GFR changes are detectable by 4-hour

creatinine clearances Patel BM, et al: Anesthesiology 2002;96:576-82

I th ARF A t l R ibl ?


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Is the ARF Acutely Reversible?


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Thadhani R, et al: NEJM 334:1448-60, 1996

Synergy & ATN Pathogenesis


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SEPSIS

R. Zager, Am J Kid Dis 1992

Renal hypoperfusion/

ischemia

Aminoglycosides

EndotoxemiaFever

Pharmacologic Approach to

Optimization of Renal Perfusion


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Optimization of Renal Perfusion

1) MAP: fluids, inotropes, pressors targeting MAP 60-

80mmHg

2) CO: fluids, inotropes to achieve adequate cardiac

output

3) Renovascular resistance: renal vasodilators

4) Corticomedullary blood flow distribution: renal

vasodilators

5) Renal tubular oxygen consumption: diuretics

(furosemide, mannitol)

ARF DDX: Prenal Azotemia vs ATN

Parameter Prerenal ATN


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Parameter Prerenal ATN

BUN/Cr ratio >20 1.018 500 mOsm /k 40 1.5 1.0Sediment H aline rare

ran casts

RTC m an

ran casts

ARF & Fractional Excretion of Urea (FEUN)


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FEUrea (%) = Uurea x Pcr x 100

Purea x Ucr

Normal, well-hydrated value: 50-65%

In ARF:

50% suggests ATN or other intrinsic renal disease

Valid even with diuretics (unlike high FENa)

Carvounis CP, et al: Kidney Int 2002;62:2223-29

PR

PR-D

ATN


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PR D

ATN

PR

PR

PR

PR-DPR-D

PR-D

ATN

ATN

Sensitivity: FENa (


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Test performance: ROC curves

U/PCr FEUN


100/179


FENaFENa

Renal Tubular KIM-1: ATN vs Normal

NORMAL ATN


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Han WK, et al: Kidney International 2002; 62:237-44

Urinary KIM-1: ATN & other Renal Diseases


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Han WK, et al: Kidney International

2002; 62:237-44

Assessing Renal Function in the Hospital

Real-time markers of renal blood flow, GFR, and injury arenot yet clinically available in the ICU


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y y

Monitoring of renal perfusion and function in ICU shouldcombine clinical assessment of several indices:

Urine output and fluid balance GFR estimates

Blood markers (creatinine, urea, cystatin C, aminoglycosides)

Changes in plasma cystatin C are probably more sensitive than otherserum markers to detect acute renal dysfunction

Abbreviated urinary clearance measurements (creatinine, urea) Tubular function indices (urine chemistries)

FEUN improves assessment of tubular function is diuretic-treated ARFpatients

Tubular injury indices (urine sediment microscopy, emerging markers)

Other plasma electrolytes which become dysregulated in the presence of renaldysfunction (particularly potassium, phosphate, bicarbonate)

Dynamic changes in these parameters should be used to assesseffects of events or interventions on renal perfusion and function

Case #2: Laboratory Data

Transthoracic contrast echocardiogram: Large multilobulated mass in the RV apex


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Large multilobulated mass in the RV apex

Severely dilated RV, severely decreased performance, septalflattening

Severe tricuspid regurgitation No valvular vegetations or interatrial shunting. Severe tricuspidregurgitation was also noted.

Na 134 / K 5 / Cl 101 / HCO3 13 / BUN 60 (52 prev. day) / Cr 3 (2.6

prev. day) / FENa 2% / FEUN 48% / U:P creatinine ratio 6:1 Glucose 104 / AG 20 / Ca 7.2 / PO4 5.9 / Mg 1.9

WBC 37.2 / Hct 31 / Plts 435K

PTT 70 / Albumin 2.3 / amylase 468 / lipase 398 TBili 0.7 / AlkP 107 / AST 919 / ALT 526 / CPK 79

U/S: normal kidneys, biliary tree, liver

ARF Interventions: Whats Available?


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Phase: primary prevention (prophylaxis) vs secondary

prevention (therapy)

Etiology: ischemic vs. nephrotoxic vs. mixed

Setting: ICU vs. Perioperative vs. Radiocontrast vs.

Other (Renal transplant, Cirrhosis, Nephrotoxins-endogenous or exogenous)

Mechanism: perfusion vs. cytoprotection vs.

regeneration vs. other

Phases of Ischemic ARF


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Molitoris BA: J Am Soc Nephrol 2003;14:265-267

Pharmacologic Approach to Optimization

of Renal Perfusion


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of Renal Perfusion 1) MAP: fluids, inotropes, pressors targeting

MAP 60-80mmHg

2) CO: fluids, inotropes, vasodilators to achieve

adequate cardiac output

3) Renovascular resistance: renal vasodilators

4) Corticomedullary blood flow distribution: renal

vasodilators

5) Renal tubular oxygen consumption: diuretics

(other effects: loop diuretics, mannitol)

Acute Right Heart Syndromes

Acute pressure overload( h b i f i i )


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p PE (thrombus, air, fat, amniotic, tumor)

ARDS

Post-cardiac surgery

Acute-on-chronic pulmonary hypertension

Chronic pulmonary diseases

Chronic thromboembolism

Primary pulmonary hypertension

Sleep-disordered breathing

RV systolic dysfunction

RV infarction

Acute Right Heart Syndromes


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Schmidt GA, Wood LDH, Principles of Critical Care 1998

Acute RV Failure Management

1. Preserve Systemic Blood PressureV


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Vasopressors

Inotropes

2. Optimize RV Preload CRRT > IHD

3. Reduce RV Afterload

High FIO2 Pulmonary Vasodilators

4. Specific Therapies Thrombolysis for P.E.

Mechanical support (RVAD) for failing ventricle

ARF Prevention: Fluids

Effect of Fluids for ARF PreventionR di t t h th 0 45% li


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Radiocontrast nephropathy: 0.45% saline

Solomon R, et al: NEJM 1994;331:1414-1416

Higher PAP improved early renal allograft function Carlier M, et al: Transplantation 1982;34:201-204

Gelatin-based colloid not hetastarch prevents * septic ARF

Schortgen F, et al: Lancet 357:911-16, 2001

Albumin prevents ARF in cirrhotics with SBP

Sort P, et al: NEJM 341:403-9, 1999

No difference in RRT Days (0.52.3 vs 0.42), new organ

dysfunction, survival with saline vs albumin in 6997 pts

SAFE Study Investigators: NEJM 2004;350:2247-56

FACTT Trial

ARDSNetwork trial


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Fluids and Catheters Treatment Trial

2 X 2 factorial design in Acute Lung Injury patients

CVC vs PAC

Fluid Conservative vs Fluid Liberal CVP


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No difference in mortality or renal function (creatinine, urine output)

with either supranormal CO/DO2 or maintenance of SVO2 70% with

dobutamine versus control in 762 ICU patients

Gattinoni L, et al: NEJM 1995;333:1025-32

Increased mortality with supranormal oxygen delivery (dobutamine)

versus control in 100 ICU patients (54% vs 34% mortality)

Hayes MA, et al: NEJM 1994;330:1717-22

Early Goal-Directed Therapy

Improved survival in septic shock pts. randomized to E.R. resuscitation

titrated to normalize SCVO2 (

70%, using dobutamine, transfusion) vsstandard care (CVP >8-12; MAP>65mmHg; UOP >0.5ml/kg/hr)

Rivers E, et al: NEJM 345:1368-77, 2001

Rivers E, et al:

NEJM 345:1368-77, 2001


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Normal Autoregulation


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RBFRBF

GFRGFR

MAP (mm Hg)

0 100 200

1.0

0.1Flowrate(L/min)

g

Renal Effects of NE in Human Septic Shock

No adequate clinical trialsI UOP ith BP i ft l i


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Increase UOP with BP increase after replacingdopamine

[Martin C:Chest;1993;103:1826-31; DesjarsP:CCM:1987;15:134-7]

Increased UOP (23ml/hr to 66ml/hr) and CrCl

(29ml/min to 71ml/min) after 24 hours NE therapy [Desjars P: CCM 1989;17:426-29]

Increased CrCl (75ml/min baseline, 89ml/min 24hrs,102ml/min 48hrs)

[Redl-Wenzl, Int Care Med 1993;19:151-4]

Pressor effect of NE vs DopamineParam eter N E

Baseline

N E E ffect D O PA

Baseline

D O P A

25 /k /

m in

D O P A +

N E


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m in

M A P

m m H

5410 8913a

538 5910 888a

C I

L/m/m2

5 .31 .3 5 .51.2 5 .41 .1 5 .51 .0 5 .91.6

S V R I

d n .sec/cm

5.m

2

659221 1150350a

647197 659217 1092337a

U O P

ml/hour

227 15351a

246 8 .210 106100a

Lactate

mmol /L

4 .81 .6 4 .41.8 4 .83 .2 4 .22 .0 3 .82.0

M artin et a l: Chest 1993 ;103:1826-31


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Patel BM, et al: Anesthesiology 2002;96:576-82


119/179

Patel BM, et al: Anesthesiology 2002;96:576-82


120/179

Patel, BM, et al: Anesthesiology 2002;96:576-82

ARF Prevention/Therapy: Vasodilators Renal vasodilators have no proven benefit in ARF

Dopamine


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Dopamine has not been proven to prevent or ameliorate ARF in any

setting

Kellum, JA & M. Decker J: Crit Care Med 29:1526-1531, 2001

ANZICS Group: Lancet 2000; 356: 2139-43

ANP

Large trials failed to demonstrate a benefit of ANP for..

RCN prophylaxis

Kurnik BR, et al: Am J Kid Dis 1998;31:674-80

ATN therapy Allgren RL, et al: NEJM 1997;336:828-34

Lewis J, et al: Am J Kid Dis 2000;36:767-74


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Kellum, JA & M. Decker J: Crit Care Med 2001;29:1526-1531

ANZICS Trial of Low-Dose Dopamine in ICU

Patients with Early Renal Dysfunction (Lancet, 12/00)

328 ti t t i l i 23 A t li d N Z l d


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328 patient trial in 23 Australian and New Zealand

intensive care units

Randomized, double-blind, placebo-controlled trial

ICU patients with SIRS (systemic inflammatory

response syndrome) and acute renal dysfunction

Dopamine 2g/kg/min versus placebo infusion until:

1) RRT; 2) Death; 3) SAE judged related to trial

infusion; 4) SIRS and renal dysfunction resolved for

24 hrs; 5) ICU discharge

ANZICS Dopamine Trial Design(ANZICS Trial, Lancet 2000)

Primary outcome: peak serum creatinine reached


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during trial infusion

13 Secondary outcomes: to be discussed

Initial sample size of 115 per group for 80% power to

detect 20% decrease in peak SCr with dopamine

(=0.05) Based on pretrial 6 center observational study

Two blinded interim analyses increased size to >300patients for 90% power to detect a 25% difference in

peak SCr

Baseline Characteristics (ANZICS Trial, Lancet 2000)

61 1763 15Age (yrs)

Placebo (n=163)Dopamine (n=161)Characteristic


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40.34 19.8940 21S. Urea (mg/dl)

2.06 0.922.07 0.96S.Cr (mg/dl)

69 %68 %Oliguria

86 %86 %Mech. Ventilation

63 %58 %Shock

13 714 8CVP (mmHg)

80 1680 15MAP (mmHg)21 821 6APACHE II

61 1763 15Age (yrs)


126/179

ANZICS Group, Lancet, Dec 2000

200

250

(ml/hr)


127/179

DP PL DP PL DP PL DP PL0

50

100

150

Baseline >1hr >24hr >48hr

U

rineOutput(



128/179


Blood Flow and Interstitial O2 Content: Regional

Distribution in Cortex/Medulla

4 2 ml/


129/179

PaO2

10-20

PaO2

+ 50

1.9 ml/

gm/min

4.2 ml/

gm/min

Brezis M, Rosen S: N Engl J Med 1995;332:647-655

ARF Prevention/Therapy: Vasodilators

Fenoldopam DA-1-specific dopaminergic agonist Small pilot trials suggested that fenoldopam improves RBF +/or GFR


130/179

Small pilot trials suggested that fenoldopam improves RBF +/or GFRduring and after.

CABG: Halpenny M, et al: Anaesthesia 2001;56:953-60 AAA repair: Halpenny M, et al: Eur J Anaesthesiol 2002;19:32-9

Radiocontrast: Tumlin JA, et al: Am Heart J 2002;143:894-903

The CONTRAST trial in 315 patients found no effect of fenoldopam

vs placebo for RCN prevention Stone GA, et al: JAMA 2003;290:2284-91

In another pilot study, Tumlin and colleagues found a 10% absoluteincrease in dialysis-free survival (63% vs 73%, p=0.22) in 155

patients with early ARF in the ICU, treated with fenoldopam vsplacebo

ASN abstract, 2003; Am J Kidney Disease, in press 2005.

ANP for post-cardiac surgery ARF


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Sward K, et al: Crit Care Med 2004 32:1310-5

ANP for post-cardiac surgery ARF


132/179

Sward K, et al: Crit Care Med 2004 32:1310-5

ARF Prevention/Therapy: Diuretics

Loop Diuretics Prophylactic furosemide infusion increases rate of ARF after CABG


133/179

(Lassnigg, JASN), or radiocontrast (Solomon, NEJM; Weinstein,

Nephron) Small trials have failed to demonstrate a benefit of loop diuretics for

ARF prevention or therapy

Mannitol Mannitol does not prevent perioperative ARF, except before renaltransplant reperfusion

Van Valenberg PL, et al: Transplantation 1987;44:784-88

Weimar W, et al: Transplantation 1983;35:99-101

Increased RCN rate c/w 0.45% saline alone (Solomon)

Common use in myoglobinuria not based on RCT data

Comparative Efficacy of Saline, Mannitol and

Furosemide in RCN Prophylaxis


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R. Solomon, et al: NEJM 1994


135/179


136/179

A Lassnigg, et al: JASN 11: 97-104, 2000

Diuretic Cocktail for post-cardiac surg. ARF


137/179

Sirivella, et al: Ann Thorac Surg 69:501-6

ICU/Perioperative ARF Prevention

Nephrotoxins/Insults

Endogenous

Rhabdomyolysis Tumor lysis Sepsis


138/179

Rhabdomyolysis, Tumor lysis, Sepsis

Mechanical ventilation: lung-protective ventilation is alsorenoprotective

ARDSNet: NEJM 2000;342:1301-08

Ranieri VM, et al: JAMA 2000;284:43-44

Glycemic control: decreased ARF and RRT with tight control Van Den Berghe G, et al: NEJM 2001;345:1359-1367

Krinsley JS: Mayo Clinic Proc 2004;79:992-1000

Exogenous

Aminoglycosides: daily dosing

Amphotericin: liposomal

Chemotherapies, Radiocontrast, NSAIDs

Kidney-Lung Protective Ventilation?

ARDSNET Tidal Volume Trial In addition to improved survival and ventilator-free days,

low V group had more days without circulatory


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low VT group had more days without circulatory,

coagulation, and renal failure (renal: 2011 vs. 1811 days,p=0.005)

ARDSNet: NEJM 2000;342:1301-08

Lung-Protective Mechanical Ventilation Strategy Less inflammation in Lung Protective Strategy group Ranieri VM, et al: JAMA 1999;282:54-61

Fewer pts. with organ system failure, and markedly fewerwith renal failure (p


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IGF-1 Clinical Studies in ARF

54 patient double-blind RCT of IGF-1 SQ q12h X 72h,beginning in ICU post-aortic surgery Fewer patients had post-op decline in renal function within 72 hours

(22% IGF-1 vs 33% placebo p


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(22% IGF 1 vs 33% placebo, p


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vasoactive drug strategies should be used to prevent or reverse

ARF There are no definitive studies supporting the use of renalvasodilators or diuretics for ARF prophylaxis or therapy

Several evolving aspects of ICU management apparently alter

the risk of ARF (ventilator management, glycemic control) Cytoprotective, antiinflammatory, regenerative therapies have

not been adequately studied

Combination therapies (eg. vasodilator plus antiinflammatory)or management protocols (eg. goal-directed therapy of ARF),are also largely untested

Indications for RRT

Uremia Encephalopathy

P i diti

Prevention of uremiccomplications

Pre ention of


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Pericarditis

Bleeding diathesis

Volume Overload

Hyperkalemia Metabolic Acidosis

Severehyperphosphatemia

Intoxications

Prevention of

uncontrolled positivefluid balance

Non-renalindications

100% -

80%

60%

100% -

80%


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60%

40%

20%

0%

60%

40%

20%

0% 0 1 2 3 4

Number of failed organs

Simple ANP ICUARF trial setting

RA Star, Kidney Int, 1998

DiffusionDiffusion


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Diffusion:Diffusion: The movement of solutes from a higher to aThe movement of solutes from a higher to a

lower solute concentration area.lower solute concentration area.

HemodialysisHemodialysis

to waste


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Blood InBlood In(from(from

patient)patient)

Blood OutBlood Out

(topatient)

DialysateDialysate OutOut

DialysateDialysate InIn

LOW PRESS

LOW CONC

HIGH PRESS

HIGH CONC

100

80

% Survival


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80

60

40

20

0 || | | | | | | | | | | | | | | | | | | |

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

CCF ICU ARF Score

LOW Kt/V urea

HIGH Kt/V urea

CCF ScoreOutcome


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Schiffl H, Lang S, Fischer R: NEJM 346:305-310, 2002


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150/179


HD Hypotension Hemodialysis-associated

Osmolality Rapid/excessive solute loss

Low sodium dialysis solution

Hemodialysis-independent

Hypovolemic: excessivedecreases in blood volume

Non-dialytic volume loss


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Cardiovascular Reflexes Bezold-Jarisch Reflex

Dialysate Temperature

Dialysate Calcium Vasodilators

NO, Adenosine, Acetate

Membrane Reaction Rare complications:

Hemolysis, Air Embolism

Rapid or excessive UF Cardiogenic: cardiac dysfunction

Arrhythmia

Systolic

Diastolic: including ischemia,

LVH, tamponade

Valvular: aortic stenosis

Impaired Vasoconstriction

Autonomic dysfunction,

Sepsis, Anaphylaxis, Meds

Standard Hemodialysis

Intracellular fluid Extracellular fluid Dialyzer


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Golper, TA 1999

Osmolality320 mosmol/kg Osmolality320 mosmol/kgfalling to 290mosmol/kg asdiffusion occurs

Step 3Water movement Step 1

Step 2

Isosmoticloss ofsolutesand water

Isolated Ultrafiltration

Intracellular fluid Extracellular fluid Dialyzer


153/179

Golper, TA 1999

Osmolality320 mosmol/kg Osmolality320 mosmol/kgwith rising plasmaoncotic pressure

Step 3Water movement Step 1

Step 2

Isosmoticloss ofsolutesand water

Approach to HD Hypotension Protocol for standard crystalloid, mannitol, albumin doses

(= empiric fluid challenge)

Vasopressor titration may be anticipated


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Consider Hypovolemia incorrect volume status assessment

consider hemorrhage (GI, retroperitoneal, hemothorax)

Consider Cardiac dysfunction

Arrhythmia / Systolic / Diastolic / Valvular

Consider Sepsis, Anaphylaxis, Addisons RRT Rx: transfusion, sodium modeling, high calcium

bath, cool dialysate, IUF or sequential IUF-HD, CRRT

UltrafiltrationUltrafiltration


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UltrafiltrationUltrafiltration:: The movement of fluid through a membraneThe movement of fluid through a membrane

caused by a pressure gradient.caused by a pressure gradient.


Blood InBlood In


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(from patient)(from patient)

Blood OutBlood Out

to waste (to patient)

LOW PRESSLOW PRESS HIGH PRESSHIGH PRESS

Fluid VolumeFluid Volume

ReductionReduction

Therapy OptionsTherapy Options

SCUFSCUF

AccessAccess

ReturnReturn


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SlowSlow



EffluentEffluent

Solute Removal by ConvectionSolute Removal by Convection


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Convection:Convection: The movement of solutes with a waterThe movement of solutes with a water--flow,flow,

solventsolvent--dragdrag, e.g, e.g the movement of membranethe movement of membrane--permeablepermeable

solutes withsolutes with ultrafilteredultrafiltered water.water.


Blood In


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to waste

Repl.

Solution

Blood In

(from patient)

Blood Out

(to patient)

LOW PRESSLOW PRESS HIGH PRESSHIGH PRESS

Clearance

Therapy OptionsTherapy Options

CVVHCVVH

AccessAccess

ReturnReturn

ReplacementReplacement


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VenoVeno--VenousVenousHemofiltrationHemofiltration

EffluentEffluent

CRRT (vs. IHD) Indications

Vasodilatory Shock Cardiogenic Shock

Right heart syndromes


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ARDS Fluid balance, Buffering, ? Antiinflammatory therapy

Cerebral Edema

Severe Hyperphosphatemia

Prevention of Post-dialytic Rebound Intoxication

Lithium

Tumor Lysis, Rhabdomyolysis, Tissue Necrosis

Septic Shock ?

HD vs. CRRT: Hemodynamic Stability

2 0H D

H D


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0 1 2 3 4 5- 3 0

- 2 0

- 1 0

0

1 0 C A V H

P D

Change

inDO2

%

D u r a t io n o f t r ea t m e n t (h o u r s )

CRRT: Intracranial Pressure

MeanICP

%

1 5 0

2 0 0

2 5 0

H D H D

C A V H

P D


163/179

0 1 2 3 4 56 0

8 0

1 0 0

1 2 0

MeanCP

P

%

D u r a t i o n o f t r e a t m e n t ( h o u r s )

0 1 2 3 4 55 0

1 0 0

Phosphate Clearance

1 4

1.6

1.8

2.0H i g h - fl u x H D (p o l y s u l fo n e )

4 h p o s t-H D

P r e - H D

16

20

C A V H D 4 L / h (p o l y a c r i lo n i tr il e )

dl)


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0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

P i c h e tte e t a l : A J K D , 1 9 9 4

D e S o i & U m a n s : A J K D , 1 9 9 3

4 h p o s t H D

E n d - H DN a d i r

SerumP

hosphate(mM)

0 8 16 24 32 40 48 56 64

0

4

8

12

C h e m o t h e r a p y

Serum

Phosphorus(mg/d

T i m e (H o u r s )

Post-dialysis Rebound

4

5

H D s ta r t

L)

4

5

C A V H D F

L)


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0 6 12 18 24 30 36 420

1

2

3

E n d - H D

H D r e s ta r t

T im e (h o u rs )

E n d - H D

Ser

umL

ithium(

mEq/L

0 8 16 24 32 40 48 56 640

1

2

3

Ser

umL

ithium(

mEq/L

T im e ( H o u rs )

Case #2: CRRT Initiation

Femoral dual-lumen 16.5cm catheter

Pre-filter CVVH mode, BFR 250ml/min

UFR 3000ml/hour (~ 42 ml/kg/hour)


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No additional anticoagulation (on IV heparin) Fluid balance: 100ml/hour net fluid removal

Pre-filter Replacement fluid: prepared by Pharmacy from base

NaCl 100mEq/L, KCl 2mEq/L, Na Bicarbonate 50mEq/l,MgSO4 3mEq/L, dextrose 1g/L

Calcium drip via central vein

50ml of 10% CaCl2 in 100ml NS

Start at 20 ml/hour


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Ronco et al, Lancet, July 2000


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Ronco et al, Lancet, July 2000

Alveolus

Pulmonary edemagenesis


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Edema Flow =[(Pmv-Pis) - ( mv - is) ] Kf

Alveolus LVEDP

Pmv mv

Pisv is

CRRT Fluid Balance Management

CRRT was initiatied to control fluid


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balance and azotemia..removingfluid to achieve the lowest filling

pressures and PEEP compatible withadequate systemic oxygenation and

perfusion on a non-toxic FIO2 .

(ml)

2750

2250

1750

*P


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Mitchell, et al., Am Rev Respir Dis 1992

EVLW

| | | | | | |

0 12 24 36 48 60 72

1250

750

250

TIME (hours)

* * * *

ityof

entilation

1.0

0.8

0.6

Routine (n=42)

Protocol (n=40)


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Probabil

Mec

hanicalV

| | | | |

0 10 20 30 40

0.4

0.2

0.0

Days of Mechanical Ventilation

einginIC

U

1.0

0.8

0.6

Routine (n=49)

Protocol (n=52)


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Probabilityofb

| | | | |

0 10 20 30 40

0.4

0.2

0.0

Days in ICU


HD vs. CRRT: Fluid Balance

6 4

6 5

H D

C A V H


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0 4 8 1 2 1 6 2 0 2 46 0

6 1

6 2

6 3

6 4 C A V H

Bodyw

eight(kg)

T i m e ( h o u r s )

Supportive Therapy Issues in Septic

CRRT Patients High glucose PD solution

adversely effects glycemiccontrol

CRRT i d d h th i


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CRRT-induced hypothermiahas mixed effects

Increases SVR and BP

Possible cerebral protection Masks fever

Antibiotic clearance by CRRT(>30ml/min CrCL, higher fluxmembranes) differs from,often exceeds intermittent HD

Van den Berghe G, et al. N Eng J Med 2001;345:1359-1367

Calgary Sun Thu July 8, 2004Alberta's chief adviser on health quality has released new recommendations for

the handling of potassium chloride in hospitals. Dr. John Cowell, CEO of theHealth Quality Council of Alberta released his findings after the deaths of two

patients at the Foothills Medical Centre earlier this year.

"The recommendations released today result from an ongoing review of the best

practices and safety guidelines for the handling of potassium chloride containing

products from five of the leading countries in terms of patient safety initiatives "


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products from five of the leading countries in terms of patient safety initiatives,Cowell said.

Among the recommendations, the health regions are being asked to immediately

implement system safeguards as outlined by the the Institute for Safe Medication

Practices' potassium chloride safety recommendations.The recommendations also say the regions should use commercially pre-

mixed dialysis solutions wherever possible.

In instances where they aren't available commercially,the dialysis solutions

must be prepared only in the hospital pharmacy under rigorous quality

assurance conditions.

Calgary Health Region officials declined to comment yesterday, saying they had justreceived the report and would comment on it later in the week.

An outside report into the deaths released last week cleared the Calgary Health

Region of any wrongdoing, citing unavoidable human errorand listed 66

recommendations which the CHR has vowed to implement

Calgary Sun Thu July 8, 2004


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recommendations which the CHR has vowed to implement.

On March 25, 83-year-old Kathleen Prowse died after being inadvertently injected with

a dialysis mixture containing potassium chloride rather than sodium chloride.

It was later discovered 53-year-old Bart Wassing had died from the same error a

week earlier.

"More remains to be done, and the Council will be promoting the development of

overall guidelines for the reporting, disclosure and review of any medication incident in

Alberta's health system," Cowell said.

The HQCA will issue further recommendations on medication safety practices in the

fall.

Case #2: Subsequent Hospital Course POD #1: Postoperative pulmonary hypertension and fluid

overload managed with nesiritide, 150-200ml/hour negative

balance, withdrawal of vasopressin POD #2: Reexplored for Hb drop from 8g/dl to 6g/dl, no

bleeding source found, heparin held

POD #3:


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POD #3: UOP continued 10-15ml/hour

Citrate anticoagulation added on CRRT Day 8

PA catheter and dobutamine discontinued CRRT Day 9

CRRT stopped Day 10, with UOP 15-45/hour, BP 123/70, CVP7

Next day: UOP 35ml/hour, BUN/Cr 26/1.1

Extubated, transferred to floor, and discharged home duringsubsequent week

Last BUN / Creatinine 10 / 0.5

Summary: Approach to ARF Incidence: at least 10% to 30% in ICU

Mortality: >50% in ICU Etiology:

Prerenal azotemia > acute tubular necrosis (ATN) >> others in hospital-acquired cases

Acute glomerulonephritis and vasculitides are more common causes ofARF de eloping o tside the hospital tho gh still less common than


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Acute glomerulonephritis and vasculitides are more common causes ofARF developing outside the hospital, though still less common thanprerenal, ATN.

Differential diagnosis: based on site of lesion (pre-, intra-, or post-renal).

Prophylaxis and careful monitoring of high-risk patients is important Care of ARF patients is supportive; the nondialytic measures includemaintenance of nutritional, volume, and electrolyte homeostasis

Emergent RRT: indicated when pulmonary edema, hyperkalemia, refractoryacidosis, or symptomatic uremia develops

Prophylactic RRT: considered with sustained anuria, persistent oliguriawith progressive azotemia and GFR

murray casestudiesinnephrology

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