powerpoint presentation vanmassenhove-rrt i… · · 2018-03-2323/03/2018 1 rrt in the critically...

23/03/2018

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RRT in the critically illJill Vanmassenhove

28-03-2015

Expensive

Care

“ I hate to tell you this, but that

should be INTENSIVE Care”

When to

start?Techniques Efficiency

and doseAnticoagulation Drug

dosingComplications Conclusion

When to




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When to

start?General1 Intoxications2 Specific clinical

conditions3

When to


conditions3

Epidemiology

Wald/AJKD/2015

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When to


conditions3

WHEN TO START= OBVIOUS?

“We’re al little concerned about your

potassium levels”

Factors influencing the decision to start RRT

Clinical symptoms

Solute level

BUN

sCr

Interval between ICU/hospital admission and RRT initiation

Days between biochemical diagnosis of AKI and RRT

Severity of AKI

AKIN/RIFLE classification

Prognostic scores

Number of organ failure

Availability of equipment and personnelMacedo/Seminars in Dialysis/2011

When to


conditions3

Advantages and shortcomings of earlier RRT initiation in AKI

Advantages ShortcomingsMore effective reversal of volume expansion, particularly in diuretic-resistant patients

Better control of electrolyte and acid base status

Pro active clearance of toxic low andmiddle molecular weight solutes

Avoidance of AKI-related emergencies, (eg cardiac dysrhythmias related tohyperkalemia

Exposure to complications associated withsupplemental vascular access (both at time of insertion and therafter- infections, thrombosis, emboli,…)

Exposure to complications associated withRRT (e.g. intradialytic hypotension, dysrhythmias, clearance of antibiotics-hypokalemia, hypoglycemia…..)

Higher cost, especially if patient was destined to recover kidney function

Adapted from Wald, Bagshaw, Semin Nephrol 36:78-84, 2016

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When to


conditions3

DO WE START TOO LATE?

…BUT HOW DO WE DEFINE

EARLY VS LATE?

When to


conditions3

Karvellas/CC/2011

Early initiation of RRT may have a

beneficial effect on survival

ELAIN AND AKIKI TRIALS: COMPARISON OF “early” VERSUS

“delayed” RRT

ELAIN AKIKI

Gaudry/NEJM/2016Zarbock/JAMA/2016

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Differences in design and methods between ELAIN AND

AKIKI

Bagshaw/Nat Rev Nephrol/2016

Mendu/CJASN/2017

Hemodialysis Hemofiltration Hemoperfusion

Solubility water water Water or lipid

Molecular

weigth

<500 Da <40.000 Da < 40.000 Da

Protein

binding

Low (<80%) low Low or high

Volume of

distribution

<1L/kg <1L/kg <1L/kg

Endogenous

clearance

<4ml/min/kg <4ml/min/kg <4ml/min/kg

Distribution

time

short longer short

When to


conditions3

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De Pont/Curr Opin Crit Care/2007

When to


conditions3

Mégarbane/Open Access Emergency Medicine/2010

Fomepizole-

CH2OH

AldDH

ADH

HCHO

HCOO-

CO2 + H2O

Methanol

Formaldehyde

Formate

Folate

Metabolic

acidosis

Blindness

Coma

When to


conditions3

Fomepizole dosing in adult patients

1.Patients not requiring hemodialysis

Initial dose: 15mg/kg IV followed by 4 doses of 10mg/kg every 12 hours

Maintenance dose: 15mg/kg IV every 12 hours thereafter until levels of methanol (or ethylene

glycol) are reduced below 20 mg/dl, and the patient is asymptomatic with normal pH

2. Patients requring hemodialysis

-Dose at the beginning of dialysis

<6 hours since last fomepizole dose: do not administer dose, ≥6 hours: administer next scheduled

dose, during dialysis: administer every 4 hours or as a continuous infusion 1 to 1.5 mg/kg/h

-Dose at the time hemodialysis is completed

<1h between last dose and the end of hemodialysis: do not administer dose at the end of

hemodialysis

1-3h between last dose and the end of hemodialysis: administer half of next scheduled dose

>3h between last dose and end of hemodialysis: administer next scheduled dose

Maintenance dose off hemodialysis: give next scheduled dose 12 hours from last dose

administered

When to


conditions3

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Recommendations for hemodialysis in ethylene glycol and

methanol poisoning

Arterial pH<7.10

Drop in arterial pH >0.05 resulting in a pH outside the normal

range despite bicarbonate infusion

Inability to maintain arterial pH > 7.3 despite bicarbonate therapy

Decrease in bicarbonate concentration >5mmol/l, despite

bicarbonate therapy

Renal failure (sCr > 265 µmol/l or rise in the sCr by > 90 µmol/l)

Deteriorating vital signs despite intensive supportive care

Visual or neurological impairment in case of methanol poisoning

Initial plasma methanol concentration > 50 mg/dl

Rate of methanol decline < 10 mg/dl per 24 hours

When to


conditions3

When to


conditions3

When to


conditions3

CRUSH Pathogenesis of ATN in

rhabdomyolysis

Toxic effect of urinary myoglobin

Hypotension (renal ischemia)

Myoglobin and urate crystal

formation at low urine pH

Protease release from injured

muscle

Lipid peroxidation

? Free radical formation

? Release of renal

vasoconstrictor substances

Warren/Muscle and Nerve/2002

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When to


conditions3

Zeng/Cochrane database of systematic reviews/2014

When to


conditions3

Dialysate circuit

Dialysate circuit

Blood circulation

Albumin circuit

diaFLUX Dialysor

diaMARS® AC250

Adsorber (charcoal)

diaMARS® IE250

Adsorber

(Ion exchanger)

MARS®FLUXDialysor

When to


conditions3

Albumin

bound

Water soluble

Bilirubin Ammonia

Bile acids Aromatic

amino acids

Indoxylsulfate Creatinine

Middle chain

and short

chain fatty

acids

IL-6

Para cresol Tryptophan

Protoporphyrin GABA

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When to


conditions3

When to


conditions3

HELIOS

(Prometheus)

and RELIEF

(MARS) trials:

no difference in

outcome

When to


conditions3

Glycogen

AminoacidsG6P

Pyruvate + H+

NADH + H+

Glucose

Protein

Urea

+

NAD+

Lactate + H+

+LDH

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When to


conditions3

Salpeter/Cochrane database of systematic reviews/2010;Heaf/Clin Diab/2011

When to


conditions3

De Vriese/JASN/1998

Cytokine Removal during CVVH in sepsis

Inflammatory

cytokines

Anti-

Inflammatory

cytokines

When to


conditions3

Borthwick/Cochrane Database of Systematic Reviews/2013

High-volume haemofiltration for sepsis

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When to




When to




General

concepts1 Duration and time

interval2Techniques

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General


interval2Techniques

General


interval2Techniques

General


interval2Techniques

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General


interval2Techniques

General


interval2

MW

SC

β2MG

12000

0,5

0,6

Ureum

60

vitB12

1230

1

High FluxLow flux

Techniques

General


interval2Techniques

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General


interval2

SCUF

Qb=100-250 ml/min

Quf=5-15 ml/min

Techniques

Costanzo/JACC/2007

Bart/NEJM/2012

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General


interval2

CVVH

Qb=100-250 ml/min

Qf=15-60 ml/min

Techniques

Cerebral oedema in

acute (<48 h)

hyponatremia

Osmotic demyelinsation in

chronic (<48 h)

hyponatremia

Osmotic demyelinisation

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General


interval2

CVVHD

Qb=50-250 ml/min

Qf=1-5 ml/min

Qd=15-30 ml/min

Techniques

General


interval2

Qb=50-200

ml/min

Qf=10-30 ml/min

Qd=15-30 ml/min

CVVHDF

Techniques

General


interval2Techniques

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General


interval2Techniques

General


interval2

Advantages Disadvantages

No need for anticoagulation Less efficient for treating acute

problems such as hyperK or flash

pulmonary edema

IP administration of drugs Not an option after abdominal and

mostly also not after cardiac surgery

Technically simpler Protein losses

No risk of vascular acces related

problems such as air embolism or

thrombus

Potential leakage

Less hemodynamic instability-

potentially better renal recovery

Not suitable for treating acute

intoxications

Can be an option for patients with

diuretic resistant heart failure

Not a good option for extremely

catabolic patients

Can allow for ascites removal in liver

cirrhosis patients

Can be problematic in case of

underlying respiratory failure

Techniques

Gabriel/KI/2008

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General


interval2

CONTINUOUS=SUPERIOR?

Techniques

Wald/AJKD/2015

Epidemiology

General


interval2

Rabindranath/Cochrane database of systematic reviews/2007

Techniques

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General


interval2Techniques

General


interval2

Schefold/CC/2013

Techniques

General


interval2Techniques

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Wald/Crit Care Med/2014

Renal recovery in Continuous versus intermittent therapies

Liang/CJASN/2016

Renal recovery in Continuous versus intermittent therapies

General


interval2

HYBRID techniques?

EDD

SLED

SLEDDf

IHD CRRT

Techniques

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Author Kumar

et al

Marshall

et al

Marshall

et al

Berbece

et al

Treatment name EDD SLED SLEDD-f SLED

Hours/day 7.5 12 8 8

Days/week 6-7 6-7 4-7 6

Qb (ml/min) 200 100 300 200

Qd (ml/min) 300 200 200 350

Replacement fluid

(ml/min)

- - 100 17

General


interval2

Berbece/KI/2006

Techniques

EDD versus CRRT

Zhang/AJKD/2015

Ricci/2008/CCM

General


interval2Techniques

A B

C D

Increase

frequency!

Increase

duration!

Increase

duration and

increase

clearance!

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General


interval2

CRRT SLED p value

Morning sCr after

day 3 (µmol/l)

136±49 120±55 0.06

Time averaged sCr 136±49 95±49 0.03

Weekly Kt/V 7.1±2.1 8.4±1.8 <0.001

EKRj (ml/min) 31±10 31±7 NS

EKRjc (ml/min) 28±9 29±6 NS

Berbece/KI/2006

Techniques

Kumar/AJKD/2000

General


interval2

COMPARISON OF MAP DURING EDD VS. CVVH.

0

10

20

30

40

50

60

70

80

90

100

preMAP midMAP endMAP

CVVH

EDDP=NS P=NS P=NS

Techniques

Kumar/AJKD/2000

General


interval2Techniques

PERCENTAGE OF TREATMENT DAYS

REQUIRING INOTROPIC SUPPORT

0

10

20

30

40

50

60

70

80

90

100

1 Inotrope 2 Inotropes 3+ Inotropes

CVVH

EDD

% o

f tr

ea

tme

nt d

ays

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When to




When to




Clearance21 Dose in acute

RRT 3DialyzerEfficiency

and dose

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RRT 3Dialyzer

Un

mo

dif

ied

ce

llu

los

e

Syn

theti

ca

lly

mo

dif

ied

ce

llu

los

eS

yn

the

tic

Efficiency

and dose



and dose

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RRT 3Dialyzer

Classification of clearance and dialysance

Dialyzer clearance

Instantaneous (cross-dialyzer) clearance

Integrated time-averaged clearance, kt/V

Single-pool clearance

Double-pool clearance

Patient clearance and eKt/V

Ionic (conductivity) dialysance

Continuous equivalance of clearance

Efficiency

and dose


RRT 3Dialyzer

Bi B0

K= (Cbi – Cbo)/Cbi)xQb + (Cbo/Cbi)xQuf

Instantaneous clearance ≠ solute removal

Efficiency

and dose

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RRT 3Dialyzer

Integrated time-averaged clearance=Kt/V

Efficiency

and dose


RRT 3Dialyzer

V x C

V= total body water

KRC

KDC

G

d(VxC) = G- KxC

dt

SINGLE POOL Kt/V

Efficiency

and dose

URR=1-post SUN/pre SUN= 1-0/80=1

After 2h of diaysis:

Kxt=20L and Kt/V=0,5

URR=1-40/80=0,5

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Kt/V=-ln(1-URR)


RRT 3Dialyzer

V x C

V= total body water

KRC

KDC

G

d(VxC) = G- KxC

dt

SINGLE POOL Kt/V

Efficiency

and dose

Kt/V=-ln(R-0.008.t)+(4-3,5R) (UF/W)


RRT 3Dialyzer

V1

C1

KR

KD

G

d(C1V1) = G- C1(KD+KR) + KC(C2-C1)

dt

d(C2V2) = -KC(C2-C1)

dt

V2

C2

KC

QF

DOUBLE POOL Kt/V

Efficiency

and dose

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RRT 3Dialyzer

CONTINOUS EQUIVALENT OF CLEARANCE-EKR

G

TAC

COMPARISON OF DIFFERENT MODALITIES

AND SCHEDULES

Efficiency

and dose

Casino/NDT/1996

Casino/NDT/1996

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Casino/NDT/1996


RRT 3Dialyzer

Blood

Dialysate

Membrane

Diffusive force

D = QB x (CBi-CBo)

CBi-CDi

Dialysance (D) (ml/min)

Efficiency

and dose


RRT 3Dialyzer

Ionic Dialysance (D) (ml/min)

Based on changes in the conductivity of the

dialysate after a step up or a step down in

dialysate sodium concentration

Dialysance of sodium is assumed to equal urea

clearance

Efficiency

and dose

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RRT 3Dialyzer

Characteristics of ideal urea kinetic expression for RRT

dose in AKI

-Kinetic equivalence for irregular/frequent IHD or differing

RRT therapies

-Independent from the assumptions of urea steady state

-Normalization for patient urea distribution volume to allow

dose comparisons between patients of different size

-Easy to calculate without compromise in accuracy

-Possibility to include residual renal urea clearance if present

Efficiency

and dose

Himmelfarb/KI/2002


RRT 3Dialyzer

Alternate dayhemodialysis (n=80)

Daily hemodialysis(n=80

p value

Mortality(N/%) 37(46) 22(28) 0.01

Resolution of acute renal failure (days)

16 ± 6 9 ± 2 0.001

Efficiency

and dose

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Ronco/Lancet/2005


RRT 3Dialyzer

Group 3: 45 ml/kg/h

Group 2: 35 ml/kg/h

Group 1: 20 ml/kg/h

Efficiency

and dose

Palevsky/NEJM/2008


RRT 3Dialyzer

CVVHDF 35ml/kg/h versus CVVHDF 20 ml/kg/h

SLED/IHD 6/week vs SLED/IHD 3/week

Efficiency

and dose

Bellomo/NEJM/2009


RRT 3Dialyzer

CVVHDF 40ml/kg/h versus

CVVHDF 25 ml/kg/h

Efficiency

and dose

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Evanson/AJKD/1998



and dose



and dose

When to




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When to




General1 Citrate2 HIT3Anticoagulation

General1 Citrate2 HIT 3Anticoagulation

KDIGO AKI guidelines/KI/2012

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General1 Citrate2 HIT 3

KDIGO AKI guidelines/KI/2012

Anticoagulation

Liu/Critical Care/2016

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Liu/Critical Care/2016



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“Risk for thrombosis in the days to weeks after stopping

heparin therapy is at least 20% and possibly as high as

50% in HIT patients who present with isolated

thrombocytopenia”Hirsch/Arch of Int Med/2004

Anticoagulation

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O’shea/Seminars in dialysis/2003

Anticoagulation


Fischer/Hemodilaysis Int/2007

Anticoagulation

When to




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When to




When to




Patient related factors

Drug-protein complexes and

molecular weight

Volume of distribution

Device related factors

When to




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molecular weight



When to






molecular weight



When to






molecular weight



When to




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molecular weight



When to




When to




Matuszkiewicz-Rowinska/Pol Archiv Med Wewn/2012

AUC24/MIC

Cmax/MIC

%T>MIC

When to




Killer characteristics?

Time-dependent killing

(e.g. Beta lactams)

Concentration-dependent

killing (e.g. Gentamycin)

%T>MIC Cmax>MIC

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1990s 2015

Low-permeability dialyzers High-permeability dialyzers

Dialysis dose not quantified Kt/Vurea target≥1,2

Dialyzer membranes less

compatible

Dialyzer membranes more

compatible

Smaller surface area dialyzers Larger surface area dialyzers

CAPD CCPD

Lower effluent volumes CRRT Higher effluent volumes CRRT

Mueller/Clin Pharmacol Ther/2009

INCREASE IN DRUG

CLEARANCE

1990s 2015

When to




When to




Böhler/KI/1999

Hemofiltration:

Postdilution mode

Hemofiltration:

Predilution mode Hemodialysis

Drug Clearance=

ultrafiltration rate

Drug Clearance=

UF rate x (blood flow/

Blood flow + SF flow rate)

Drug Clearance depends

on molecular weight

Pharmacokinetic principles during continuous treatments

When to




Other factors to

consider

-Protein binding

-Blood Flow

-Larger membrane

surface area

-Different membrane

charge

-Thinner membrane

material

-Adsorption

Böhler/KI/1999

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Choi/2010/Blood Purification

Choi/2010/Blood Purification

When to




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When to




When to




Complications Technical1 Clinical2

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Technical complications

of RRT in the ICU

Vascular access problems

Air embolism

Hemolysis

Electrolyte and Acid-Base

Disorders


Insertion site Complications of insertion Disadvantage

Internal jugular Punction carotid artery

Pneumothorax(PT),

Hemothorax(HT)

Rupture superior VC

Trendelenburg required

More prone to infectious

complications, especially in

patients with trachetomy

Femoral Punction femoral artery

Retroperitoneal hematoma

Infection

Highest infectious rate?

Highest recirculation rate

Only for bed-bound patients

Subclavian Punction subclavian artery

Risk of PT, HT

Rupture superior VC

Technically difficult

High rate of central venous

stenosis

Trendelenburg required


Hoste/JASN/2004

Bloodstream

infection

No Bloodstream

infection

p=0.53

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BMI<28: femoral

BMI>28: jugular



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Clinical complications of RRT

in the ICU

Bleeding and thrombosis

Hypoxemia

Hypotension

Biocompatibility

Hypersensitivity reactions

Dialysis Dyequilibrium Syndrome

Prolongation of renal recovery

Nutritional and metabolic

problems

Cardiac arrhythmias

Febrile reactions

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Clinical complications of RRT

in the ICU

RCA metabolic complications

Hypophosphataemia

Hypocalcemia

Hyper- or Hypomagnesemia

When to




When to




• No strict criteria for RRT start but a too precocious start of RRT is not helpful and might cause further damage to an already injured kidney.

• No clear benefit for continous over intermittent therapies. SLED probably a good alternative

• Treshold dose is important but beyond that no additional benefit when increasing dose

• Acute PD can be considered, especially in case of heart failure and liver cirrhosis with ascites

• RRT is not a harmless technique

• Think about adapting drug dosage

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