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Expérimentation innovante en

Transplantation Hépatique: ERAS

Service de Chirurgie Digestive et Hépato-Bilio-Pancréatique

Raffaele BRUSTIA

Olivier SCATTON

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INTRODUCTION

ERAS EN TRANSPLANTATION

HEPATIQUE

INDICATEURS/OUTCOMES

CONCLUSION

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INTRODUCTION

ERAS EN TRANSPLANTATION

HEPATIQUE

INDICATEURS/OUTCOMES

CONCLUSION

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L’innovation en santé c’est aussi…

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Ljungqvist JAMA Surgery, 2017

INNOVATION ORGANISATIONNELLE EN CHIRURGIE?

ERAS AND COLORECTAL (656 publications)

ERAS AND LIVER SURGERY (179 publications)

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Evidence-Based Guidelines

• patient education

• goal-directed fluid

management

• decreased use of

unnecessary NG tubes and

drains

• minimal use of opioid

analgesia

• early mobilization

• resumption of oral intake

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WHICH OUTCOMEs IN ERAS?

CRITERE DE JUGEMENT IMPACT EFFET

Durée Hospitalisation ✔ 20-50 %

Taux de complications ✔ 30-60 %

Impact économique ✔ 0-70%

Brustia et al. J Visc Surg 2018

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• ERAS nouveau mode de prise en charge

• Critères de jugement

– Récupération

– Morbidité

– Médico-Eco

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INTRODUCTION

ERAS EN TRANSPLANTATION

HEPATIQUE

INDICATEURS/OUTCOMES

CONCLUSION

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MORBIDIT

E

DUREE

SEJOUR

TRANSPLANTATION HEPATIQUE?

COUTS DE

SANTE

STANDARD

S

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INNOVATION ORGANISATIONNELLE EN TH?

ERAS AND COLORECTAL (656 publications)

ERAS AND LIVER SURGERY (179 publications)

ERAS AND LIVER TRANSPLANTATION (2 publications) - 47%

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Guidelines for Perioperative

Care

for Liver Transplantation 1_preoperative_counselling

2_prehabilitation

3_perioperative_fasting_and_carbohydrate_loading

4_antimicrobial_prophylaxis

5_antithrombotic_anticoagulation_prophylaxis 6_anesthetic_premedication

7_incision

8_portocaval_shunt 9_short_acting_anesth

10_perioperative_analgesia

11_early_extubation

12_abdominal_drainage

13_fluid_blood_managment 14_perioperative_normothermia

15_nasogastric_intubation

16_PONV

17_early_nutrition_supplementation

18_early_mobilisation

19_glycemic_control 20_postoperative_ileus 21_postoperative_education

22_AUDIT

Literature screening n°2271 references => n° 43 full text included

Raffaele Brustia, Olivier Scatton. Systematic review for perioperative care in liver transplantation - Enhanced Recovery After Surgery (ERAS). PROSPERO 2019 CRD42019132798

Dr Monsel – Dr Skurzak

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Expert panel

Mean (SD) 15.7 (7.86)

N=21

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0

10

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40

50

60

70

80

90

100

Round 1

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0 10 20 30 40 50 60 70 80 90

100

ROUND1 ROUND2

Round 2

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A systematic review and meta-analysis64 reported a significant increase in the absolute risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients with cirrhosis, compared to those without. Retrospective data found veno-venous bypass, antifibrinolytic medication and pulmonary artery hypertension as risk factors for PE during or early after LT 65,66. To date there is no direct evidence in favour or against thrombotic prophylaxis early after LT. Evidence derived from liver surgery37,67,68 suggest that the use of compressive stockings and intermittent pneumatic compression devices may be effective and safe against DVT. Early ambulation and optimal hydration can be safely recommended as general measures against DVT69, being therefore part of ERAS recommendations. Recommendations There is no evidence in favour or against thrombotic prophylaxis, but compressive stockings and intermittent pneumatic compression devices during LT may be recommended. Evidence level Very Low Recommendation grade Weak

An example = Antithrombotic prophylaxis

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ERAS EN TRANSPLANTATION HEPATIQUE

• Nouveau mode de prise en charge/parcours de soins coordonné

• Quelques études pilotes

• Recommandations en cours

• Méthode d’évaluation?

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INTRODUCTION

ERAS EN TRANSPLANTATION

HEPATIQUE

INDICATEURS/OUTCOMES

CONCLUSION

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WHICH OUTCOMES IN LT? Patient reported outcomes

Recovery Graft dysfunction

Mortality

Brustia R, Dechartres A, Scatton O, HPB 2020

Morbidity CRITERE DE

JUGEMENT

IMPAC

T

Durée

Hospitalisation ✔

Taux de

complications ✔

Impact économique ✔

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DMS après TH: QUEL STANDARD?

4 13 26 33 60

Lee, Korea

Laiz, Spain

Parik, US Uemoto,

JP Muller,

Benchmark*

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RECUPERATION FONCTIONNELLE

HOSPITALISATION

DELAI DE RECUPERATION FONCTIONNELLE

DUREE D’HOSPITALISATION

IMS*

*Indication Médicale de Sortie

Step 1 Exploring functional recovery Discussion with experts

Step 2 Exploratory e-Delphi study Restricted panel

Summary of functional recovery in LT

Step 3 Pilot, field study

Proposal: 10 points - Functional recovery checklist criteria

Consensus based 10 points - Functional recovery checklist criteria

Prospective assessment of the 10 points - functional recovery checklist: strengths and weaknesses

Step 4 Validation e-Delphi study Extended panel

Extended Panel identification via official networks

Restricted Panel identification via networks and snowballing

Proposal: 10 points - Functional recovery checklist criteria

Pragmatic, Consensus based 10 points - Functional recovery checklist criteria

Aim To develop a pragmatic, consensus-based checklist to assess functional recovery after liver transplantation

Design Mixed-method study: (1) literature review and expert discussion to draft first checklist criteria; (2) an exploratory online e-Delphi study with a restricted interdisciplinary panel of experts; (3) a small-scale field study to test the feasibility ; and (4) a validation e-Delphi study with an extended interdisciplinary panel of experts.

Figure 1, Study Design

Literature review of functional recovery

in Liver Surgery

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STEP 1 = Exploring functional recovery

Author Year Study Comparaison N°pt Lap/Open LoS (days) F. recovery

(days) Pain

control Solid food

Mobility Biology No

perfusion

No fever

Wong1 2014 Cohort

ERAS high compliance vs

low compliance

165 L-O 7 5 X x x x x

Jones2 2013 RCT ERAS vs control

91 L * 4 vs 7 * 3 vs 6 x x x x

Dasari3 2015 Cohort ERAS vs control

184 L-O 6 vs 6 5 vs 5 x x x x x

Liang4 2016 RCT ERAS vs

control (Lap.) 187 L * 6 vs 10 * 5 vs 8 x x x x

Ratti5 2016 Cohort ERAS open

vs ERAS lap. vs control (HCC)

207 L-O * 4 vs 6 * 3 vs 5 x x x x x

Wong6 2017 RCT ERAS Open vs

Lap (LLS) 24 L-O

* 4 lap vs 4.5 open

3 vs 3 x x x x x

Pt=patients, RCT=randomized clinical trial, Lap= laparoscopy, LLS=Left Lateral Sectionectomy, y=years, *= significative statistical difference, LoS=length of stay

TABLE 2 Results of the preliminary e-Delphi, n= 9 participants.

Round 1 Round 2

DISCHARGE CRITERIA % agreement % agreement

1 Adequate pain control with oral analgesics 89% 100%

2 Independently mobile 89% 100%

3 Tolerance to solid food 89% 100%

4 Absence of uncontrolled surgical complications 78% 100%

5 No IV perfusion 89% 100%

6 Normal/declining TB, ALT, AST, and a PT > 80% 89% 100%

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Residual Tacrolimus 5<ng/ml<10 on two consecutive controls 78% 100%

8 Compliance with therapeutic education 89% 100%

9 No immunosuppressive-induced adverse effect 67% 100%

10 Normal postoperative imaging 67% 100%

IV=intra venous, TB=total bilirubin, ALT= alanine aminotransferase, AST= aspartate aminotransferase, PT=prothrombin time, IQR=inter quartile range

STEP 2 = Exploring functional recovery

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TABLE 3 General characteristics of the cohort.

Patients N=45 % (n)

RECEIVER

MELD score, median (IQR) 11.5 (8.0-16.5)

Postoperative complications, Clavien-Dindo

I 20% ( 9) II 22% (10) III 9% ( 4) IV 2% ( 1) ICU stay, days, median (IQR) 5.0 (4.0-8.0) PRIMARY OUTCOME Functional recovery, days, median (IQR) 14.0 (11.0-20.0) Hospital stay, days, median (IQR) 18.0 (14.0-21.0) Gap, days, median (IQR) 3.00 (1.00-4.00) Gap, % 14.3 (5.9-23.5) Y=years, BMI=body mass index, MELD=model for end stage liver disease, RBC=red blood cells, LT=liver transplantation, ICU=intensive care unit, IQR=inter quartile range

STEP 3 = Pilot Field study

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STEP 3 = Pilot Field study

TABLE 4 Discharge criteria.

Patients N=45 Fulfilled at discharge % (n)

Completion days, median (IQR)

1 Adequate pain control with oral analgesics 100% (45) 6.0 (3.0-9.0) 2 Independently mobile 100% (45) 7.0 (5.0-10.0) 3 Tolerance to solid food 100% (45) 4.0 (3.0-7.0) 4 Absence of uncontrolled surgical complications 100% (45) 9.0 (5.0-15.0) 5 No IV perfusion 100% (45) 9.0 (6.0-15.0) 6 Normal/declining TB, ALT, AST, and a PT > 80% 100% (45) 5.0 (4.0-8.0) 7 Residual Tacrolimus 5<ng/ml<10 on two consecutive controls 47% (21) 13.0 (9.0-15.0) 8 Compliance with therapeutic education 100% (45) 11.0 (7.0-15.0) 9 No immunosuppressive-induced adverse effect 96% (43) 9.0 (6.0-12.0) 10 Normal postoperative imaging 98% (44) 10.0 (7.0-17.0) IV=intra venous, TB=total bilirubin, ALT= alanine aminotransferase, AST= aspartate aminotransferase, PT=prothrombin time, IQR=inter quartile range

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STEP 4 = Validation e-Delphi study - Extended panel

60

56

66

6

10

128

0 50 100 150 200

Round 3

Round 2

Round 1

Number of panelists

Responders Non responders

14.49.1

GREF2 - ACHBT

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CRITÈRES “PATIENT” 1. Contrôle de la douleur satisfaisant par analgésie orale (EVA < 4/10) 2. Mobilisation indépendante (marche seul sans aide, ou capable de s’habiller seul ou avec assistance minime) et capable de rejoindre le Service de Transplantation en cas de symptômes d’alarme (fièvre, douleur, ictère). 3. Tolérance à l’alimentation per os (autrement dit, le malade est capable de manger une quantité minimale et suffisante pour éviter de devoir le perfuser. Exemple=yaourt, compote, repas léger). 4. Absence de complications chirurgicales majeures ou complications infectieuses non contrôlées. 5. Absence de perfusion.

CRITÈRES “GREFFON”. 6. Diminution de bilirubinémie totale, ASAT, ALAT et Temps de Prothrombine > 80% par rapport aux valeurs avant TH 7. Dosage résiduel du Tacrolimus plasmatique (T0) 5<ug/L<10, sur au moins deux prélèvements consécutifs avant la sortie. 8. Education thérapeutique adaptée au patient, concernant tous les traitements inhérents à la TH (par exemple traitement immunosuppresseur, contrôle de la glycémie, ou traitement par insuline si nécessaire.) 9. Absence d’effets indésirables majeurs du traitement immunosuppresseur. (e.g., insuffisance rénale, surdosage en Tacrolimus, cytopénie). 10. Imagerie de contrôle normale (Echo-Doppler ou Scanner) avant la sortie.

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STEP 4 = Validation e-Delphi study - Extended panel

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

round_1 round_2 round_3

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3 Tolérance à l’alimentation

per os

• autrement dit, le malade est capable de manger

une quantité minimale et suffisante pour éviter de

devoir le perfuser.

• Exemple=yaourt, compote, repas léger.

Tolérance digestive à

l’alimentation

• Une alimentation par voie orale ou entérale est possible

sans entraîner de nausées, reflux, régurgitations ou

vomissements nécessitant de limiter les apports.

• les apports liquidiens par voie orale ou entérale sont

suffisants pour assurer l'équilibre hydro-électrolytique,

sans nécessité de perfusion intraveineuse.

• en cas d'alimentation exclusivement par voie orale, le

patient est capable d'ingérer au moins un repas-type par

jour (comprenant au moins un plat de résistance, ex:

"purée-jambon"); il prend ses repas seul ou, en cas

d'autonomie limitée, une aide à la prise des repas est

possible.

• lorsqu'une nutrition artificielle par voie entérale, nocturne

et/ou diurne, est nécessaire, sa mise en œuvre à domicile

est possible sans délai.

STEP 4 = à propos d’un critère…

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INTRODUCTION

ERAS EN TRANSPLANTATION

HEPATIQUE

INDICATEURS/OUTCOMES

CONCLUSION

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ERAS = nouveau mode de prise en charge

ERAS en TH = recommandations en cours

RECUPERATION FONCTIONNELLE = Critère de

jugement validé

raffaele . brustia @ aphp . fr