CRRT for AKI and non AKI patients in the ICU - …vnaccemt.org.vn/files/media/201804/RoomA-A02... · Courtesy of Pr. Didier Journois . Hemoconcentration in CVVH leads to the formation

CRRT for AKI and non AKI patients in the ICU

Thomas RIMMELE – MD PhD

Anesthesiology and Intensive Care Medicine

Edouard Herriot Hospital

LYON, FRANCE

[email protected]

April, 12 2018 – Dalat, Viet-Nam

mailto:[email protected]



Conflicts of Interest

Scientific partnership with the following companies:

- Baxter

- Fresenius Medical Care

- Bbraun

- Nikkiso

- Bellco-Medtronic

- Biomérieux

CRRT approach: what are your goals for your CRRT sessions?

Goals How to achieve the goals?

Hemodynamic stability IHD vs CRRT

Appropriate dose Prescribed vs Delivered dose

- Stability of the RRT session over time - Limited risk of bleeding and metabolic disorders

Anticoagulation strategy

optimization of the molecular clearances over time CVVH vs CVVHD

Modulation of the inflammatory status? Extracorporeal blood purification therapies for sepsis

Improvement of other organ dysfunctions? RRT-associated therapies

Individualization/personalization of the therapy Quality measures for reassessment of prescription

Non AKI patients: Efficient blood purification in toxicology IHD vs CRRT vs hemoperfusion













CRRT IHD

IHD vs CRRT:a 20-yr controversy

• Avoids risks associated with continuous anticoagulation

• (Easily deployed at the bedside)

• Allows the patient to achieve greater mobility

• Cheaper “per se”

Advantages of IHD Advantages of CRRT

• Greater hemodynamic stability

• Continuous control of volume status

• Steady control of electrolyte and acid-base status

• Temperature control

• Avoidance of solute swings and cerebral edema

• Superior uremic control

RRT modality (CRRT vs IHD)

KDIGO guidelines. Kidney Int suppl 2012

Friedrich et al. Crit Care 2012

RRT modality and mortality

a OR, crude b OR, adjusted for age, sex, diabetes or heart failure before admission and calendar year c OR, adjusted for age, sex, diabetes or heart failure before admission, calendar year, hospital type and main diagnosis at ICU

Renal failure among patients surviving 90 days:

Bell et al. Intensive Care Med 2007

Wald R et al. Crit Care Med 2014

Cumulative risk of chronic dialysis among critically ill patients with AKI surviving to 90 days after commencement of RRT who were initially treated with CRRT vs IHD:

Outcomes for patients with AKI surviving to 90 days, initiated on CRRT vs IHD:

Variable Odds ratio (95% CI) p

Technique (IHD vs CRRT) 0.912 (0.835–0.996) 0.04

Shock (yes vs no) 1.188 (1.060–1.331) 0.003

Vasopressors (yes vs no) 1.192 (1.088–1.305) 0.0002

Ventilation (yes vs no) 1.541 (1.404–1.692) <0.0001

Cardiac arrest (yes vs no) 1.243 (1.009–1.531) 0.0413

Cardiac surgery 1.676 (1.281–2.192) 0.0002

Non terminal CKD (yes vs no) 0.635 (0.575–0.702) <0.0001

Center (<250 vs >450 beds) 0.547 (0.427–0.702) <0.0001

Multivariate analysis: 1 million ICU patients over 4 years

Bonnassieux et al. Crit Care Med 2017












Chapter 5.8: Dose of RRT in AKI

5.8.3: We recommend delivering a Kt/V of 3.9 per week when using intermittent or extended RRT in AKI. (1A)

5.8.4: We recommend delivering an effluent volume of 20-25 ml/kg/h for CRRT in AKI (1A). This will usually require a higher prescription of effluent volume. (Not Graded)

KDIGO guidelines. Kidney Int 2012

Dose of RRT

Dose of RRT

Dose of RRT

Administered dose / Prescribed dose

Initiation of CRRT 25 ml/kg/h 35 ml/kg/h

Nursing Treatment stopped 2 to 3 times / day (1h)

24 ml/kg/h 33 ml/kg/h

Bag changes (dialysate/Effluent/substitution fluid) (1h)


Scheduled stops (surgery – CT scan – New session…) (>1h)


NON scheduled stops (circuit thrombosis – cathéter problem…) (>1h)

<< 20 ml/kg/h 25 ml/kg/h

Courtesy of Dr. O. Joannes-Boyau












Monchi et al. ICM 2004 Kutsogiannis et al. Kidney Int 2005

Stucker et al. Crit Care 2015 Gattas et al. Crit Care Med 2015

Citrate and filter life span

Citrate efficacy: electronic microscopy

Capillary fiber with heparin Capillary fiber with citrate

Wu et al. Am J Kidney Dis 2012

Schilder et al. Critical Care 2014

Stucker et al. Critical Care 2015

Gattas et al. Crit Care Med 2015

Citrate =

- Less bleeding complications

- Higher filter life time

- Less unwanted stops = optimized administered dialysis dose

Anticoagulation and KDIGO guidelines

KDIGO guidelines. Kidney Int 2012

Any issue(s) with citrate?

Risk of metabolic complications

Trisodic Citrate (Na3Citrate)

Cit-Ca2+

Complex

Na+ +++++

Strong Ion Difference

SID = (Na+ + K+ + Ca2+ + Mg2+ + UA+) – (Cl- + UA-)

- Metabolic alkalosis - Metabolic acidosis - Hypernatremia - Hypocalcemia - Hypercalcemia - Hypomagnesemia

Citrate overload or citrate

accumulation?

What is the best way to avoid these metabolic complications?

= How should I proceed to give to the patient as little citrate as

possible?

Citrate anticoagulation is now safe because pumps work together!

Blood pump and citrate pump work together

Effluent pump and calcium pump work together

FILTRATION FRACTION

Courtesy of Pr. Didier Journois

FILTRATION FRACTION

Modality of RRT (all sessions), DoRéMiFa study

CVVHDF (22%)

CVVH (13%)

IRRT (37%)

CVVHD (26%)

HVHF Pulse HVHF (0.6%) (0.8%)

Courtesy of Marlies Ostermann

Type of anticoagulation for CRRT (DoRéMiFa study)

Courtesy of Marlies Ostermann












Decrease of membrane efficacy over time

Zhang et al. ASAIO J 2013

Courtesy of Pr. Didier Journois

Hemoconcentration in CVVH leads to the formation of protein cake (polarization layer)

Clogging / Clotting

• There is clogging when some blood components accumulate inside the pores of the membrane until they totally block the pores

• => Permeability is impaired

Membrane clogging

• There is clotting when clots are large enough to block the capillary fiber

• => Circulation is impaired

Membrane clotting

= COLMATAGE

RRT modality

KDIGO guidelines. Kidney Int suppl 2012 Nothing on CVVHD versus CVVH!












Hotchkiss et al. Nat Med 2009

Septic shock: Hyperinflammation followed by severe immunosuppression

TNF, IL-6, IL-8 (early deaths) IL-4, IL-10, IL-1ra (late deaths)

- No clinical signs of this immunosuppression

- Increased risk of HAI

- 70-80% of total mortality












PROMETHEUS,MARS

ECCOR

SCUF

RRT

Cytokine Removal

From RRT to MOST (Multiple Organ Support Therapy)












Kellum JA, Ronco C. Blood purif 2016

Bagshaw et al. Blood purif 2016

CRRT precision approach: concept of dynamic CRRT dose












Small molecules Hemodialyse

Middle molecules Hemofiltration

Molecules fixed to albumine MARS/SPAD

Hemoperfusion Large molecules/IG Plasmapheresis Hemoperfusion

Pathologic cells Erythrapheresis /

Leucapheresis

The modality depends on the target!

Body water

VIC Plasma Interstitium

Importance of the distribution volume

Plasmatic water =

5 % of total body water

RRT only for plasmatic water!

RRT for toxicology: Limits

• RRT such as hemodialysis / hemofiltration poorly efficient if:

• Large distribution volume

• Molecules very lipophilic

• Molecules bound to proteins

• Very large molecules

Convection vs diffusion

• Limitation of CVVH : Filtration fraction

Convection vs diffusion

• Limitation of CVVH: Filtration fraction

• FF = UF flow rate / Blood flow (if 100 % post dilution)

• FF = (Pre + Post + weight loss) / (Blood flow + Pré)

• Ideal FF = 20-25 % of blood volume (30-40 % of plasmatic volume)

• In the best scenario, we can remove only 40% of the toxin when it passes through the filter

Hemoperfusion Holubek et al. Kidney Intern 2008

In clinical practice?

• Group EXTRIP

• Literature reviews and recommendations

Groupe EXTRIP

• Website

• Available publications: • 2014 : TRICYCLIQUES (Ø), BARBITURIQUES (IHD), CARBAMAZEPINE (IHD)

• 2015 : PARACETAMOL(IHD), METHANOL(IHD), LITHIUM (IHD), THALLIUM (IHD), THEOPHYLINE (IHD), SALICYLÉS (IHD), METFORMINE (IHD), VALPROATE (IHD)

• 2016 : PHENYTOINE (HDI), DIGOXINE (Ø)

CRRT for AKI and non AKI patients in 2018

1- Hemodynamic stability CRRT+++ - The use of CRRT (as the initial modality in the ICU) seems to be associated with better recovery after severe AKI 2- RRT dose: Distinguish prescribed dose from delivered dose! 3- Bleeding risk and metabolic disorders - Citrate should be the first choice for CRRT anticoagulation in most cases - CVVHD allows for an extension of indication thanks to a reduced blood flow rate 4- Diffusion or convection? CVVH leads to protein cake. CVVH means FF to calculate and to pay attention to. 5- Inflammatory status - Extracorporeal blood purification as an adjuvant treatment for sepsis? Several promising techniques under investigation 6- Organ dysfunctions RRT-associated therapies are currently under investigation. The curent level of evidence for these therapies is low 7- Precision medicine Implementation of quality measures of CRRT in clinical practice to regularly reassess the prescription in order to individualize the therapy 8- RRT for toxicology indications: IHD +++++

Documents

CRRT for AKI and non AKI patients in the ICU - …vnaccemt.org.vn/files/media/201804/RoomA-A02... · Courtesy of Pr. Didier Journois . Hemoconcentration in CVVH leads to the formation