Dr. M.A. Al-OdatJordanian Board of Medicine

Saudi ICU board fellow.

WHATIs CRRT

HOWTo use CRRT

WHAT Is CRRT

Is an extracorporeal blood purification therapy intended to substitute for impaired renal function over an extended period of time and applied for or aimed at being applied for 24 hours a day.

*Bellomo R., Ronco C., Mehta R, Nomenclature for Continuous Renal Replacement Therapies, AJKD, Vol 28, No. 5, Suppl 3, November 1996

Mimic the functions and physiology of the native organ

Qualitative and quantitative blood purification

Restore and maintain of homeostasis Avoid complications and good clinical

tolerance Provide conditions favoring recovery of

renal function

A central double-lumen veno-venous hemodialysis catheter

An extracorporeal circuit and a hemofilter

A blood pump and a effluent pump. With specific CRRT therapies

dialysate and/or replacement pumps are required.

CRRT is indicated in any patient who meets criteria for hemodialysis therapy but cannot tolerate intermittent dialysis due to hemodynamic instability.

CRRT is better tolerated by hemodynamically unstable patients because fluid volume, electrolytes and pH are adjusted slowly and steadily over a 24 hour period rather than a 3 – 4 hour period.

Hemodynamically unstable patients with the following diagnoses may be candidates for CRRT:

fluid overload acute renal failure chronic renal failure life-threatening electrolyte imbalance major burns with compromised renal function drug overdose

Vascular access. Semi-permeable membrane. Transport mechanism. Dialysate and replacement fluid.

Internal jugular. Subclavian. Femoral.

• Internal Jugular Vein Primary site of choice due to lower associated risk of

complication and simplicity of catheter insertion.

• Femoral Vein Patient immobilized, the femoral vein is optimal and

constitutes the easiest site for insertion.

• Subclavin Vein The least preferred site given its higher risk of

pneumo/hemothorax and its association with central venous stenosis.

• The length of the catheter chosen will depend upon the site used Size of the catheter is important in the pediatric

population. • The following are suggested guidelines for the

different sites:RIJ= 15 cm FrenchLIJ= 20 cm FrenchFemoral= 25 cm French

The basis of all blood purification therapies. Water and some solutes pass through the membrane, while

cellular components and other solutes remain behind. 2 types: cellulose and synthetic. Synthetic membranes allow clearance of larger molecules

and are the primary type used in CRRT. Filters are changed when they become contaminated,

clogged or clotted.

(Dalton) 100000 50000

10000 5000

1000 500 100

50

10

Albumin (55000 – 60000)

Beta 2 Microglobulin (11800) Inulin (5200)

Vit B12 (1355)

Aluminium/Desforoxamine complex (700)Glucose (180) Uric Acid (168) Creatinine (113) Phosphate (80)

Urea (60) Potassium (35) Phosphorus (31) Sodium (23)

The passage of water through a membrane under a pressure gradient.

Driving pressure can be +ve (push fluid through the filter), or –ve (pull fluid to other side of filter).

Pressure gradient is created by effluent pump.

Movement of solutes through a membrane by the force of water “solvent drag”.

The water pulls the molecules along with it as it flows through the membrane.

can remove middle and large molecules, as well as large fluid volumes.

maximized by using replacement fluids.

To better understand this phenomenon, think of a quiet stream as compared to a raging river. The stream could never shift a boulder, but the powerful raging river could easily drag a boulder downstream. So it is with convection; the faster the flow through the membrane, the larger the molecules that can be transported

Adsorption is the removal of solutes from the blood because they cling to the membrane. Think of an air filter. As the air passes through it, impurities cling to the filter itself. Eventually the impurities will clog the filter and it will need to be changed. The same is true in blood purification. High levels of adsorption can cause filters to clog and become ineffective

Diffusion is the movement of a solute across a membrane via a concentration gradient. For diffusion to occur, another fluid must flow on the opposite side of the membrane. In blood purification this fluid is called dialysate. When solutes diffuse across a membrane they alwaysshift from an area of higher concentration to an area of lower concentration until the solute concentration on both sides of the membrane is equal.

Dialysate is any fluid used on theopposite side of the filter from theblood during blood purification.As with traditional hemodialysistherapy, the dialysate is run on theopposite side of the filter, countercurrent to the flow of the patient’s blood. The countercurrent flow allows a greater diffusion gradient across the entire membrane,increasing the effectiveness of solute removal.

Typical dialysate flow rates are between 600 – 1800 mL/hour.

Used to increase the amount of convective solute removal in CRRT.

Replacement fluids do not replace anything. Fluid removal rates are calculated independently of

replacement fluid rates. The most common replacement fluid is 0.9%

Normal Saline. Can be pre or post filter.

The decision to infuse replacement fluids before or after the filter is made by the physician. Replacement fluids administered pre-filter reduce filter clotting and can be administered at faster rates (driving higher convection) than fluids administered post-filter. The downside of pre-filter replacement fluids is that they invalidate post-filter lab draws; the lab results willshow the composition of the replacement fluid rather than that of the effluent.

The primary indication for SCUF is fluid overload without uremia or significant electrolyte imbalance.

The main mechanism of water transport is ultrafiltration.

Other solutes are carried off in small amounts, but usually not enough to be clinically significant.

the amount of fluid in the effluent bag is the same as the amount removed from the patient.

Fluid removal rates are typically closer to 100 mL/hour.

No dialysate or replacement fluid is used.

Blood flow: 80 – 200 ml/min Duration Ultrafiltration: 20-100 ml/hr (or total volume) Anticoagulation NO dialysate, NO replacement fluid

An extremely effective method of solute removal and is indicated for uremia or severe pH or electrolyte imbalance with or without fluid overload.

Particularly good at removal of large molecules, because CVVH removes solutes via convection,

Many theories exist regarding the removal of pro-inflammatory mediators by CVVH.

solutes can be removed in large quantities while easily maintaining a net zero or even a positive fluid balance in the patient.

the amount of fluid in the effluent bag is equal to the amount of fluid removed from the patient plus the volume of replacement fluids administered.

No dialysate is used.

Blood flow:80 – 200 ml/min Duration Ultrafiltration: 20-100 ml/hr (or total volume) RF: 1000 – 2000 ml/hr , pre or post filter (up to 3

lit/hr). Anticoagulation NO dialysate

Effective for removal of small to medium sized molecules. Solute removal occurs primarily due to diffusion. No replacement fluid is used. Dialysate is run on the opposite side of the filter. Fluid in the effluent bag is equal to the amount of fluid

removed from the patient plus the dialysate.

Blood flow:80 – 200 ml/min Duration Ultrafiltration: 20 -100 ml/hr (or total volume) Anticoagulation Dialysate: 600 – 1800 ml/hr (up to 3 lit/hr). NO replacement fluid

The most flexible of all the therapies, and combines the benefits of diffusion and convection for solute removal.

The use of replacement fluid allows adequate solute removal even with zero or positive net fluid balance for the patient.

Amount of fluid in the effluent bag equals the fluid removed from the patient plus the dialysate and the replacement fluid.

Dialysate on the opposite side of the filter and replacement fluid either before or after the filter.

Blood flow: 80 – 200 ml/min Duration Ultrafiltration: 20-100 ml/hr (or total volume) Anticoagulation Dialysate: 600 – 1800 ml/hr (up to 3 lit/hr). Replacement fluid: 1000-2000 ml/hr, pre or post

filter (up to 3 lit/hr).

Low-dose pre-filter unfractionated Heparin: any dose less than 5 units/kg/hour.

Medium-dose pre-filter unfractionated Heparin: a dose between 8-10 units/kg/hour.

Systemic unfractionated Heparin is administered intravenously and titrated to achieve an activated partial thromboplastin time (aPTT) ordered by the physician, for patients who have another indication for heparinization, such as. DVT

Regional unfractionated Heparin: a pre-filter dose of 1500 units/hour of Heparin, with administration of Protamine post-filter at a dose of 10-12 mg/hour.

Low-molecular-weight Heparins Prostacyclin: rarely used (expensive, hypotension) Citrate: infused pre-filter, Ca must be replaced.

Platelet count < 50,000/mm3 INR > 2.0 aPTT > 60 seconds Actively bleeding or with an active bleeding episode

in the last 24 hours Severe hepatic dysfunction or recent liver

transplantation Within 24 hours post cardiopulmonary bypass or

extra-corporeal membrane oxygenation (ECMO)

Bleeding Hypothermia Electrolyte imbalance Acid-base imbalance Infection Dosing of medications

WHATIs CRRT

HOWTo use CRRT

HOWTo use CRRT

When to start CRRT. IHD Vs CRRT. Dose of CRRT. Anticoagulation and CRRT. Nutrition and CRRT. Drug doses in CRRT. Ethical issues of CRRT.

Further studies focused mostly on the timing of initiation of CRRT

Gettings et al published a retrospective analysis of 100 consecutive patients with post traumatic AKI in 1999

Early vs late initiation based on BUN < or > 60 mg/dL at initiation of therapy

Early group CRRT initiated on hospital day 10+15 Mean BUN of 43+13

Late group CRRT initiated on HD 19+27 mg/dl BUN of 94+28 mg/dl

Survival – 39% in early Vs 20% in late group

Critical points: Non-randomized, retrospective More pts with multi-system organ failure or sepsis in late

group More pts oliguric on first day of CRRT in early than late

group, leading to suggestion that there was a confounding effect (?physician bias)

Bouman et al (2002)randomized 106 critically ill patients with AKI to three groups: Early high-volume CVVHDF (35 pts) Early low-volume CVVHDF (35 pts) Late low-volume CVVHDF (36 pts)

Two early groups – txt started within 12 hrs of meeting inclusion criteria: Oliguria x 6 hrs despite hemodynamic optimization Measured cr clearance <20 ml/min on a 3-hr timed

collection Late groups:

BUN>112 K>6.5 Pulmonary edema present

No significant differences in survival were observed Critical point is that 28-day mortality was only 27%,

much lower than in previously reported studies of critically ill patients with AKI

Small sample size lead to low statistical power Interestingly, 6/36 pts in late group never got RRT

(2 pts died and 4 pts recovered renal function)

Patients were divided into early or late dialysis groups based on an arbitrary blood urea nitrogen cut-off level of 80 mg/dL before renal replacement therapy.

Earlier initiation of renal replacement therapy, based on the predialysis blood urea nitrogen level, with continuous venous-venous hemofiltration might provide a better ICU survival rate.

Journal of the American College of SurgeonsVolume 205, Issue 2, August 2007, Pages 266-276

multi-center, randomized controlled trial with 1,508 critically ill AKI patients in Australia and New Zealand.

2 groups: higher-intensity group (CRRT dose of 40 mL/kg/hr) or a lower-intensity group (CRRT dose of 25 mL/kg/hr).

Early initiation may have contributed to excellent outcomes (mean, 50 hours).

Inadequate data available to answer this question Observational data suggests better outcomes are

associated with early RRT initiation ? If “less sick” patients are included in these early

groups Also, many patients with AKI are not treated with

RRT

Objective: The impact of CRRT and IHD on renal recovery.

Design: retrospective cohort study between the years 1995 and 2004. Follow-up ranged between 3 months and 10 years.

Patients: 2202 90 days survival: 85.7% with CRRT, 14.3% with

IHD

Conclusions: Although further study is needed, this study suggests that renal recovery may be better after CRRT than IHD for ARF.

Mortality was not affected significantly by RRT mode.

Objectives: To estimate the impact of hemodialysis modality on patient outcome.

Design: Prospective multicenter observational study conducted from March 1996 to May 1997.

28 ICUs, 587 patients, France. Conclusions: Renal replacement therapy mode was

not found to have any prognostic value. Randomized controlled trials should be undertaken

to assess this important question.

The concept of RRT dose is part of the required knowledge for a safe and effective delivery of therapy.

As is the case for antibiotics, vasopressors, anti-inflammatory drugs, mechanical ventilation, etc.

In chronic kidney disease, urea often has been used as a marker molecule.

The amount (dose) of delivered RRT can be described by various terms: efficiency, intensity, frequency, and clinical efficacy.

The volume of blood cleared of a given solute over a given time.

(mL/min, mL/hr, L/hr, L/24 hrs, etc.) During RRT, K depends on solute molecular size

and diffusivity, transport modality (convection or diffusion), and circuit operational characteristics such as blood flow rate, ultrafiltration rate, dialysate flow rate, and membrane and hemodialyzer type and size.

Defined as: The product of K X time. (Kt: mL/min X 24 hrs, L/hr X 4 hrs, etc.) Kt is more useful than K in comparing various

RRTs. Nevertheless, equal Kt products may lead to

different results if K is large and t is small or if K is small and t is large.

The effective outcome resulting from the administration of a given treatment dose to a given patient.

V: is the volume of distribution of the marker molecule in the body.

Kt/V is a dimensionless number(e.g., 3 L/hr X 24 hrs/45 L = 72 L/45 L = 1.6)

The marker solute cannot and does not represent all of the solutes that accumulate in renal failure.

Its kinetics and volume of distribution are also different from other solutes.

Finally, its removal during RRT is not representative of the removal of other solutes.

This is true for both end-stage renal failure and acute renal failure.

Brause et al. (2008), using CVVH, found that higher Kt/V values (0.8 versus 0.53) were correlated with improved uremic control and acid-base balance.

Paganini EP (2001):A mean Kt/V >1.0 was associated with increased survival.

Ronco C (2000): A randomized, controlled trial of CRRT dose, CVVH at 35 or 45ml/kg per h was associated with improved survival when compared with 20 ml/kg per h in 425 critically ill patients with ARF .

306100135

100

90

80

70

60

50

40

30

20

10

0

Group 1(n=146)

(( Uf = =20 ml/kg/hr)

Group 2 (n=139)

( Uf =35 ml/kg/hr)

Group 3 (n=140)

( Uf =45 ml/kg/hr)

41% 57% 58%

p < 0.001 p n.s.

p < 0.001

Sur

viva

lS

urvi

val

(%)

(%)

Effects of different doses in CVVH on outcome of ARF - Ronco & Bellomo study. Lancet . july 00

Bouman C et al (2002):3 groups Early high-volume hemofiltration (72 to 96 L/24 h). Early low-volume hemofiltration (24 to 36 L/24 h). Late low-volumehemofiltration (24 to 36 L/24 h).

No difference in terms of renal recovery or 28-d mortality regarding the dose.

Prevent clotting of the circuit. Preserve filter performance. Optimize circuit servival. Prevent loss of blood due to circuit clotting.

Should prevent filter clotting without inducing hemorrhage.

Should have a short half-life, and action limited to extracorporeal circuit.

Should be easily monitored. Should have No systemic side effects. Should have an antidote.

Low-dose pre-filter unfractionated Heparin: any dose less than 5 units/kg/hour.

Medium-dose pre-filter unfractionated Heparin: a dose between 8-10 units/kg/hour.

Systemic unfractionated Heparin is administered intravenously and titrated to achieve an activated partial thromboplastin time (aPTT) ordered by the physician, for patients who have another indication for heparinization, such as. DVT

Regional unfractionated Heparin: a pre-filter dose of 1500 units/hour of Heparin, with administration of Protamine post-filter at a dose of 10-12 mg/hour.

Low-molecular-weight Heparins Prostacyclin: rarely used (expensive, hypotension) Citrate: infused pre-filter, Ca must be replaced.

Kozek-Langenecker et al (2002). Fiaccadori E et al (2002). Nakae H et al (2003).

Attractive strategy that has its drawbacks

(HIT, bleeding)

5000 – 20000 U of UFH added to the priming solution.

Continuous infusion of 3-5 u/kg/hr. 50 – 100 % prolongation of aPTT. Incidence of bleeding varied between 0 – 50 %

Pre-filter citrate inhibits coagulation by chelating Ca+

As a result iCa decreases. An iCa concentration below 0.35 mmol/L is

required to inhibit coagulation.

RCT, 144 patients. Safety and efficacy of regional anticoagulation with

citrate in critically ill patients with AKF, without an increased risk of bleeding.

Nadroparin group Vs Citrate group. Hb concentration lower in N group (p=0.002) ICU mortality lower in C group than N group (25%

Vs 30% , p< 0.01) Hospital mortality lower in C group than N group

(40% Vs 48%, p = 0.065)

Prospective dose finding study. 30 patients with acute or history of HIT. ARF in need of CRRT. Safety determined by:

- steady state of BUN 32.16 ±18.02 mg/dl

- mean filter patency at 24 hrs: 98%

- Bleeding episodes.

Argatroban loading dose of 100 µ/kg Followed by maintenance infusion rate ( µ/kg/min) Maintenance infusion calculated by: 2.15 – 0.06 X APACHE II score Conclusion: In critically ill patients with HIT and

necessity for CRRT , APACHE II can help to predict the required argatroban maintenance dose for anticoagulation.

This predictor identifies decreased argatroban dosing requirements.

Resulting in effective and safe CRRT.

Anticoagulation during CRRT should be individualized.

The first goal should be the safety of the patient. Attention should be paid to non-pharmacological

means of prolonging filter life (blood flow, wide pore cath, pre-filter replacement fluid).

ARF causes anorexia, nausea, vomiting, bleeding ARF causes rapid nitrogen loss and lean body mass

loss (hypercatabolism) ARF causes ↑ gluconeogenesis with insulin

resistance Dialysis causes loss of amino acids and protein Uremia toxins cause impaired glucose utilization

and protein synthesis

Calories: 25-45 kcals/kg dry weight or REE Protein: about 10-16 g amino acids lost per day with

CRRT ARF w/o HD (expected to resolve within a few days): .6-1

g pro/kg Acute HD: 1.2-1.4 g/kg; acute PD: 1.2-1.5 g/kg; CRRT:

1.5-2.5 g/kg CHO: ~60% total calories; limit to 5 mg/kg/min;

peripheral insulin resistance may limit CHO In CWHD(F) watch for CHO in dialysate or replacement

fluids Fat: 20-35% of total calories; lipid clearance may be

impaired

Vitamin A: elevated vitamin A levels are known to occur with RF

Vitamin B – prevent B6 deficiency by giving 10 mg pyridoxine hydrochloride/day

Folate and B6: supplement when homocysteine levels are high

Vitamin C: <200 mg/day to prevent ↑ oxalate Activated vitamin D Vitamin K: give Vitamin K especially to pts on

antibiotics that suppress gut production of K

↑ potassium, magnesium, and phos occur often due to ↓ renal clearance and ↑ protein catabolism

↓ potassium, mg and phos can occur with refeeding CRRT pts can have ↓ K+, phos Mg deficiency can cause K+ deficiency resistant to

supplementation Vitamin C, copper, chromium lost with CVVH

Depends on residual renal function, fluid and sodium status, other losses

Usually 500 mL/day + urine output Fluid replacement needs can be ↑ with CRRT

only the drug in the central compartment （ plasma ） is available for extracorporeal removal

drugs with a large Vd have less access to the hemofilter or dialyzer

Extracorporeal treatmentdeeper compartments the rate of extracorporeal removal the rate of transfer between the peripheral and central

compartment.

Extracorporeal removal

Molecular weight. Volume of distribution. Plasma protein binding. Drug charge (Gibbs-Donnan effect).

Membrane. Diffusion. Convection. Adsorption to membrane.

Design: A questionnaire. Setting: The First International Course on Critical

Care Nephrology. Participants: The participants in the course (around

500).

Most participants think that establishing ethical criteria for managing CRRT is a medical task.

Many responders would start futile CRRT or maintain it if requested by the family.

Only 55% believe that informed consent is necessary for initiating CRRT.

One out of four would start or maintain unwanted life-saving CRRT.

Most think that every vital support should be withdrawn when futile