Chronic Kidney Disease: Chronic Kidney Disease (CKD) · Hypervolemia Hypovolemia 34 Principles of...

Robert N. Sladen, MBChB, FCCM

Allen Hyman Professor of Critical Care Anesthesiology

Executive Vice-ChairChief, Division of Critical Care

Director, CTICU and SICUDepartment of Anesthesiology

Columbia University Medical CenterNew York, NY

Chronic Kidney Disease:The Silent Killer?

No Disclosures

1

What is Chronic Kidney Disease?

2

Chronic Kidney Disease (CKD)

• Functional or structural kidney damage

- eGFR < 60 mL / min /1.73 m2 x 3 months

• United States: > 20 m affected (7%)

- 47% of individuals > 70 yrs

- End-stage renal disease (RRT): > 500 k

• Risk factors: diabetes; hypertension (90%)

- Risk of dying of CV disease in older patients with CKD is greater than risk of needing RRT!

Drawz P et al. Ann Intern Med 2009;150:ITC2-1-15

3

Modification of Diet in Renal Disease (MDRD)

http://www.nkdep.nih.gov

eGFR = 186 x (Scr)-1.154 x (Age)-0.203

x 0.742 (if female); x 1.212 (if African-American)

National Kidney Disease Education Program

Estimated GFR (eGFR)

4

For example: 64 yr-old woman, baseline SCr 1.9 mg/dL

eGFR = 186 x (1.9)-1.154 x (64)-0.203 x (0.742)

Estimated GFR (MDRD)

eGFR = 26.6 mL / min /1.73m2

http://www.mdcalc.com/mdrd-gfr-equation/

How severe is her CKD?

5

National Kidney Foundation (NKF)

Kidney Disease Outcomes QI Classification

CKDStage

eGFR (mL/min/1.73M2)

Description

1 > 90 Kidney damage with NL GFR

2 60 - 89 Mildly decreased GFR

3a 45 - 59 Moderately decreased GFR

3b 30 - 44 Moderately severe decrease

4 15 - 29 Severely decreased GFR

5 < 15 (or RRT) End-stage kidney disease

Levey AS et al. Ann Intern Med 2003; 139: 137-47

6

National Kidney Foundation (NKF) Kidney Disease Outcomes QI Classification

CKDStage

eGFR (mL/min/1.73M2) Description

1 > 90 Kidney damage with NL GFR

2 60 - 89 Mildly decreased GFR

3 < 60 Moderately decreased GFR

4 < 30 Severely decreased GFR

5 < 15 Kidney failure

Levey AS et al. Ann Intern Med 2003; 139: 137-47

7

For example: 64 yr-old woman, baseline SCr 1.9 mg/dL

eGFR = 186 x (1.9)-1.154 x (64)-0.203 x (0.742)

Estimated GFR (MDRD)

eGFR = 26.6 mL / min /1.73m2

http://www.mdcalc.com/mdrd-gfr-equation/

She has Stage 4 CKD …

8

Go AS et al. N Engl J Med 2004; 351:1296-1305

1.12 m adults without dialysis or transplantation

Risk of CKDCV Events

1, 23a

3b

4

5

HospitalizationDeath

9CKD CRASH 2-16 - January 24, 2016

Sladen, Robert, MBChB, FCCM Chronic Kidney Disease

Renal Risk in CABG SurgeryYeo KK et al. Am J Cardiol 2008; 101:1269-74

N = 37,7350

1

2

3

4

5

> 60 59-30 29-15 < 15

Odds Ratiofor Death

eGFR

10

Limitations of eGFR

• It is an estimated, not actual GFR!

• Provides reliable assessment of eGFR between 20 - 60 mL / min /1.73 m2 only

• GFR > 60 mL / min /1.73 m2 is referred to as “normal”

• Largely dependent on SCr

- affected by depleted muscle mass

- cannot track acute changes in GFR!

Sladen RN. Anesth Analg 2011;112:1277-9

11

How Should We Modify Our Perioperative

Management?

Top Ten Caveats

12

1. Anticipate

cardiovascular disease

13

Cardiorenal Syndrome (CRS)Ronco C. et al. J Am Coll Cardiol 2008; 52:1527-39

Type Primary Disorder

Leading to …

1 Acute CHF CKD

2 Chronic CHF CKD

3 AKI adverse cardiac events

4 CKD adverse cardiac events

5 Sepsis etc. cardiac, renal injury

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Cardiovascular Disease in CKD

• Causes 40% of all deaths in CKD

- LVH, diffuse calcinosis, fibrosis, CAD

- vitamin D deficiency contributes (Ca++)

- high incidence of arrhythmias (worsen CKD)

- increased thromboembolism, bleeding

• Silent ischemia (autonomic neuropathy)

• Risk of sudden cardiac death (20-40%)

- increases with severity of CKD

- reversed by renal transplant, but not by HD

Franczyk-Skora B et al. BMC Nephrol 2012: 13; 162.

15

• Highly protein bound, poorly dialyzed

• Toxic to kidneys and heart

• Induce oxidative stress, endothelial dysfunction

• Vascular smooth muscle cell proliferation

• Fibrogenic, pro-hypertrophic (LVH)

• Promote atherosclerosis, adverse CV events

Lekavanvijit S et al. Circ Res 2012; 111: 1470-83

Protein-Bound Uremic Toxins (PBUT) Cardiorenal Syndrome (Organ Crosstalk)

Indoxyl sulfate, p-cresol, homocysteine, ADMA

16

Indoxyl Sulfate Metabolism

• Indoxyl sulfate (from tryptophan in diet) accumulates in CKD

• Cardiotoxic

• AST-120 (Kremezin), an oral charcoal, absorbs indole in ileum

• Improves cardiac and renal function in animal CKD

Lekavanvijit S et al. Circ Res 2012; 111: 1470-83

OAT = organic anion transporter

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O

Endothelium Smooth muscle

R NOS

L-arginine

L-citrulline

sGC

GTP

cGMP

NO

VASODILATION

*

asymmetric dimethylarginine(ADMA)



Diastolic Dysfunction in CKD

• Common in CKD especially with HTN

- LVH, diffuse calcinosis, fibrosis, CAD

- increases with grade of CKD (85% stage 4-5)

• LV ejection fraction > 50%

- impaired diastolic relaxation

- evaluated by transthoracic echocardiogram

- requires higher filling pressure, slower HR

• Increased risk of cardiac mortality

Farshid A et al. BMC Nephrol 2013: 14; 280.

19

Sudden Cardiac Death (SCD)

• SV, V arrhythmias - 80-90% of patients on HD

- cardiac fibrosis, sympathetic hyperactivity

• Exacerbated during HD and hours afterwards- 50% of all deaths in HD patients

• Prolonged QT - iron overload and deposition

- Torsades des pointes, VF, asystole

- electrolyte shifts - hypokalemia, hypomagnesemia

- catecholamine bursts (hypovolemia, HD)

- drugs: antidepressants, droperidol, ciprofloxacin

Franczyk-Skora B et al. BMC Nephrol 2012: 13; 162.

20

Torsades de Pointes“Twisting of the Points”

Yap YG, Cam AJ. Heart 2003; 89: 1363-72

Multifocal ventricular tachycardia

• Prolonged QT

• Low K, Mg

• Catecholamines

• Drugs

- haloperidol

- droperidol

21

SCD: Prophylaxis

•Beta blockade

•Statins

•RAAS blockade

•AICD

Whitman IR et al. JASN 2012 23; 1929-39

22

Do A Cardiac Workup!

• Careful history (DM, HTN, CAD, arrhythmias)

• Look for anemia (EPO, iron, folate, GIB)

• ECG (QT, conduction problems, arrhythmias)

• TTE (LVH, diastolic dysfunction, CHF)

• Perioperative beta blockade

• Cardioprotective anesthetic, emergence

23

2. Anticipate autonomic neuropathy

24

Autonomic Neuropathy in CKD

• Delayed gastric emptying (aspiration risk)

• Silent myocardial ischemia

• Orthostatic hypotension

Accompanies peripheral neuropathy

25

3. Anticipate Acidosis and Hyperkalemia

26

Metabolic Acidosis in CKD

• Early: hyperchloremic acidosis- tubular HCO3 wasting

• Late: anion gap acidosis- sulfate, phosphate accumulation

• Acute on chronic acidosis- hypercarbia, shock, diarrhea, stress



Acid-Base Management

• Check preoperative HCO3 and Cl

- hyperchloremic vs. anion gap acidosis

• Support ventilatory compensation

- increase minute ventilation in OR

- consider postoperative ventilation

• Recognize relationship to potassium

28

Potassium Balance

∆ pH 0.1 ➜ ∆ K+ 0.5 mEq/L

K+ [160] K+ [4]Na ATPase

H+

K+

β-agonists

insulin

29

Perioperative Acidosis35 yr old diabetic, cadaveric renal transplant

PaCO2 pH HCO3 K+

Preop 32 7.32 17 5

OR 40 7.25 18 5.3

PACU 44 7.21 19 5.6

PACU 48 7.18 19 5.9

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Acute Hyperkalemia in CKD• Acute acidosis• Catabolic stress• Major trauma, surgery, sepsis• Drugs

- NSAIDs, ACE inhibitors- K - sparing diuretics- β-blockers- Cyclosporin A, tacrolimus

31

Hyperkalemia Protocol

Calcium chloride 1-2 g central IV

NaHCO3 50 - 100 mEq

Hyperventilate 0.1 pH = 0.5 K+

Insulin + glucose 5u + 25g (50 mL 50%)

Kayexalate enema 0.5 g/kg

Emergency dialysis If K+ > 6.0 mEq/L

32

4. Anticipate Acute Fluid Overload and Pulmonary Edema

33

Depleted Fluid Reserve

• Anuria- excess Na: edema, HTN- excess H2O: hyponatremia

• Nonoliguric, polyuric- unable to concentrate urine

Hypervolemia Hypovolemia

34

Principles of Fluid Management

• Correct fluid deficits

• Restrict maintenance fluid

• Monitor appropriately

• Be careful post-operatively!- withdrawal of positive pressure - reversal of sympathetic block

35

5. Anticipate Anemia and Bleeding



Hematologic Impact of CKD

• Chronic anemia

- erythropoietin deficiency

- chronic blood loss (HD, GIB)

- iron, folate deficiency

• Uremic thrombocytopathy

- platelet dysfunction (normal count)

- care with regional, axial anesthesia

37

Erythropoietin and CKD

• CKD-induced cardiac dysfunction

- pro-inflammatory cytokines

- anti-erythrocytic circulating factors

• Erythropoietin therapy

- anti-inflammatory, anti-oxidative

- decreased LVH, fibrosis, BNP

- excess: CVA, MI, thrombosis, ESRD, death

Arcasoy M. Br J Haematol 2008; 141:14-31

38

Uremic Thrombocytopathy

vWF

VIII

vWF VIII

platelets

Urea−

endothelium

Acquired von Willebrand’s Disease

39

Uremic Thrombocytopathy

vWF

VIII

vWF VIII

platelets

Urea−

endothelium

Acquired von Willebrand’s Disease

PressorAmines

+

40

Desmopressin (DDAVP)

• Derivative of arginine vasopressin (AVP)

- vasodilator, long-acting

• 0.3 µg/kg IV over 15-20 min (hypotension)

• Improves platelet function for 1-12 hr

• Releases vWF-VIII from endothelium

- tachyphylaxis with repeat doses

- not effective with ongoing pressor therapy

8-deamino D-arginine vasopressin

41

Cryoprecipitate• Patients exposed to amines

- NE, EPI, AVP

• Recent administration of DDAVP

• Contains VWF, Factor VIII

- also fibrinogen, Factor XIII

42

6. Anticipate renal osteodystrophy

43

Vitamin D Deficiency and CKDChonchol M et al. Ann Med 2011; 43:273-82

Vitamin D3 - cholecalciferol

• Decreased intake of dairy products

- phosphate restriction

• Decreased sunlight exposure

• Vitamin D loss with proteinuria

• Vitamin D loss in dialysate

25-OH D < 30 ng/mL

44

Vitamin D Deficiency and CKD

25-OH D 1,25-OH2 D

1-alpha hydroxylase(kidney)

anti-inflammatory innate immunity

healthy bones & joints

Chonchol M et al. Ann Med 2011; 43:273-82

less active more active

CVDinfection

osteoporosis

Vitamin D3 - cholecalciferol

X45

CKD CRASH 2-16 - January 24, 2016


Renal Bone Disease

• Vitamin D deficiency (20-80% of ESRD)

• Hypocalcemia (impaired GI absorption)

• Increased parathyroid hormone (PTH)

- mobilization of calcium from bones- metastatic calcification, osteodystrophy- brittle bones and joints- cardiac fibrosis (increased risk of CVD)

• Careful positioning and pressure protection!

Chonchol M et al. Ann Med 2011; 43:273-82

46

7. Anticipate the Impact of Dialysis

Renal replacement therapy (RRT)

47

Diffusion Convection

Dialysis Ultrafiltration

Renal Replacement Therapy (RRT)

48

Dialysis (diffusion)

Blood

Dialysate

Diffusion along Concentration Gradient

49

Dialysis (diffusion)

Blood

Dialysate

Diffusion along Concentration Gradient

Osmotic Shift

50

Convection (ultrafiltration)

Blood

Dialysate

Hydrostatic Pressure

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Blood

Dialysate

Solvent Drag

Volume Shift

Convection (ultrafiltration)

52

Diffusion Convection

Dialysis Ultrafiltration


Osmotic Shift Volume Shift

53


Peritoneal Dialysis (PD)

Continuous RRT (CRRT)

Intermittent Hemodialysis (IHD)



What Dialysis Does Well

• Pulmonary edema

• Hyperkalemia, acidosis

• Acute uremia:- encephalopathy- enteropathy- serositis- thrombocytopathy

Controls manifestations of acute uremia

55

• Cardiovascular complications (SCD)• Anemia• Renal osteodystrophy• Peripheral neuropathy• Impaired resistance to sepsis• Poor wound healing

What Dialysis Does PoorlyControls manifestations of chronic uremia

56

Timing of Preoperative Dialysis• Ideal: afternoon, the day before surgery!

• Adverse effects of dialysis:

- AV shunt (low SVR)

- hypovolemia, hypotension, SCD

- electrolyte imbalance (K, Mg, Pi)

- myocardial ischemia, arrhythmias

- dysequilibrium syndrome

- residual anticoagulation

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8. Anticipate delayed emergence and persistent neuromuscular blockade

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Renal Drug Disposition• Few drugs are totally renal dependent

- aminoglycosides, digoxin

• Many drugs are partially renal dependent (decrease maintenance doses)

- metformin, cimetidine, penicillin, milrinone

- pancuronium, vecuronium, rocuronium

- atropine, glycopyrrolate, neostigmine

• Some drugs have active metabolites- morphine, meperidine, vecuronium

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Rocuronium

• Elimination is independent of renal function

• Pharmacodynamic data are conflicting

- no difference, prolonged action, variable

• Immediately inactivated by sugammadex

- complex is excreted by kidneys

Robertson EN et al. Eur J Anaesthesiol 2005; 22: 929-32Robertson EN et al. Eur J Anaesthesiol 2005; 22: 4-10

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Morphine

Morphine-3-G

80%

antianalgesic

Morphine-6-G

10%

analgesic (40 x potency)

excreted in urine

John Sear, Oxford

Normorphine

neuroexcitatory

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Drugs Cleared in the Blood

Drug Mechanism

succinylcholine PChE

esmolol RBC esterase

cisatracurium Hoffman

remifentanil esterase

clevidipine esterase

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9. Anticipate nausea, vomiting, aspiration

and perioperative GI bleeding



Gastrointestinal Disease and CKD

• Delayed gastric emptying (aspiration risk)

- autonomic neuropathy

• GI Bleeding (increased risk and mortality):

- peptic ulcer disease (25%)

- erosive esophagitis, gastritis, duodenitis

- ischemic colitis (IHD)

- thrombocytopathy (normal count)

• Risk increases with stage of CKD

Thomas R et al. Ren Fail 2012, Oct 18 (ePub)

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10. Anticipate Postoperative

Complications

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Postop Complications• Acute kidney injury (AKI on CKD)

• Myocardial ischemia, arrhythmias

• Postoperative pneumonia

• Inability to tolerate hemodialysis

• Poor wound healing and wound infection

• Prolonged ICU length of stay

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CKDis a multisystem disease - and can be a silent killer!

Be careful out there!

The Bottom Line

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Good Luck !!

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[email protected]

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CKD CRASH 2-16 - January 24, 2016


Chronic Kidney Disease: Chronic Kidney Disease (CKD) · Hypervolemia Hypovolemia 34 Principles of...

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