LỌC MÁU LIÊN TỤC CHO BỆNH NHÂN CÓ TỔN CÓ VÀ KHÔNG CÓ TỔN THƯƠNG THẬN CẤP TẠI ICU

- Limited risk of bleeding and metabolic disorders Anticoagulation strategy optimization of the molecular clearances over time CVVH vs CVVHD?. Modulation of the inflammatory status?[r]

(1)

CRRT for AKI and non AKI patients in the ICU

Thomas RIMMELE – MD PhD

Anesthesiology and Intensive Care Medicine Edouard Herriot Hospital

LYON, FRANCE

thomas.rimmele@chu-lyon.fr

(2)

Conflicts of Interest

Scientific partnership with the following companies: - Baxter

- Fresenius Medical Care - Bbraun

- Nikkiso

(3)

(4)

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

(5)

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

(6)

CRRT IHD

(7)

• 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

(8)

RRT modality (CRRT vs IHD)

(9)

Friedrich et al Crit Care 2012

(10)

aOR, crude

bOR, adjusted for age, sex, diabetes or heart failure before admission and calendar year

cOR, 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:

(11)

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:

(12)

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 years

(13)

(14)

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)

(15)

(16)

(17)

(18)

Administered dose / Prescribed dose

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

Nursing

Treatment stopped to times / day (1h)

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

Bag changes

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

23 ml/kg/h 31 ml/kg/h

Scheduled stops

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

21 ml/kg/h 29 ml/kg/h

NON scheduled stops

(circuit thrombosis – cathéter problem…) (>1h)

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

(19)

(20)

Monchi et al ICM 2004 Kutsogiannis et al Kidney Int 2005

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

(21)

Citrate efficacy: electronic microscopy

(22)

(23)

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

(24)

Anticoagulation and KDIGO guidelines

(25)

(26)

Risk of metabolic complications

Trisodic Citrate

(Na3Citrate)

Cit-Ca2+

Complex

(27)

Strong Ion Difference

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

- Metabolic alkalosis - Metabolic acidosis - Hypernatremia

- Hypocalcemia - Hypercalcemia

(28)

(29)

(30)

(31)

Citrate anticoagulation is now safe because pumps work together!

Blood pump and citrate pump work together

(32)

(33)

FILTRATION FRACTION

(34)

(35)

(36)

Modality of RRT (all sessions), DoRéMiFa study CVVHDF (22%) CVVH (13%) IRRT (37%) CVVHD (26%)

HVHF Pulse HVHF (0.6%) (0.8%)

(37)

Type of anticoagulation for CRRT (DoRéMiFa study)

(38)

(39)

Decrease of membrane efficacy over time

(40)

(41)

(42)

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

(43)

RRT modality

KDIGO guidelines Kidney Int suppl 2012

(44)

(45)

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)

(46)

(47)

PROMETHEUS, MARS

ECCOR

SCUF

RRT Cytokine

Removal

(48)

(49)

(50)

(51)

Bagshaw et al Blood purif 2016

(52)

Individualization/personalization of the therapy Quality measures for reassessment of prescription Non AKI patients: Efficient blood purification in toxicology IHD vs CRRT vs hemoperfusion

(53)

Small molecules

Hemodialyse

Middle molecules

Hemofiltration

Molecules fixed to albumine

MARS/SPAD

Hemoperfusion Large molecules/IG

Plasmapheresis Hemoperfusion

Pathologic cells

Erythrapheresis / Leucapheresis

(54)

Body water

VIC Plasma Interstitium

Importance of the distribution volume

Plasmatic water = 5 % of total body water

(55)

RRT for toxicology: Limits

• RRT such as hemodialysis / hemofiltration poorly efficient if:

• Large distribution volume • Molecules very lipophilic

(56)

(57)

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)

(58)

Hemoperfusion

(59)

In clinical practice?

• Group EXTRIP

(60)

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)

(61)

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