H Zmamou

N Leblanc

D Levacher

J Kubiak

RECYCLING OF HIGH QUANTITIES OF WASTEPAPER SLUDGE ASH FOR PRODUCTION OF BLENDED CEMENTS AND ALTERNATIVE MATERIALS

Keywords: Wastepaper sludge ash, lime, cement, calcined kaolin, unconfined compressive strength, morphology

Among low cost and widely available raw materials, wastepaper sludge ash is of key interest as potential construction material. These materials come from the paper recycling industry. In present study, wastepaper sludge ash (WSA) retrieved from UPM Chapelle Darblay Company located in the south of Rouen, France, were subjected to preliminary physicochemical characterization by X-Ray fluorescence, laser granulometry and scanning electron microscope (SEM) imagery for particles morphology. Afterwards, the WSA considered as mineral addition was blended with cement, lime, and calcined kaolin for the highest possible dosages in WSA. The effects of reactivity were evaluated by means of mechanical strength measurements. Cylindrical samples were prepared with WSA mixtures and air-cured for 7, 14 and 28 days at ambient room temperature. WSA content ranged from 30-95%. The samples obtained were subjected to unconfined compressive strength to verify the occurrence of reactivity and resistance. The results indicated that the strength increased along the curing time for all mixtures except for the reference sample in which 100% of WSA was used. The lime addition does not impact the unconfined compressive strength. As main results, on one hand, WSA and cement based mixtures with a weight ratio of 95/5 develop 2 MPa compressive strength and more during the curing time which suit for construction materials. On the other hand, with only 5% of calcined kaolin, a value of 9 MPa was attained after 28 days indicating that mixtures with calcined kaolin can be effectively used for building materials such as bricks or blocks.

INTRODUCTION

Wastepaper sludge ash (WSA) is a residue which results from co-incineration of paper sludge generated by the paper mill, recycling paper industry and waste of wood biomass. Thousands of tons of paper sludge are produced every year around the globe and as a result, thousands of tons of WSA ash. In Europe, pulp and paper industry generate around 11 million tons of waste annually, 70% of which is derived from the production of deinked recycled paper [START_REF] Martin-Castellote | Paperchain project: Establishment of new circular economy models between pulp and paper industry and construction industry to create sustainable infrastructures[END_REF]. According to the Confederation of European Paper Industries (CEPI) and International Council of Forest and Paper Associations (ICFPA), the paper recycling rate in Europe reached approximately 72.3% in 2017 [START_REF]Latest market data demonstrates strong performance for the European pulp and paper industry in[END_REF]. UK produces over 1.5 million tons of wastepaper sludge annually for 125,000 tons/year of WSA [START_REF] Monte | Waste management from pulp and paper production in the European Union[END_REF][START_REF] Wrap | Paper Sludge Ash: A technical report on the production and use of paper sludge ash[END_REF]. In France, the WSA production for the United Paper Mills Ltd (UPM) and Norske Skog Gobley (NSG) recycling paper industries is around 60,000 tons (reduced by the half since 2017) and 50,000 tons every year, respectively [START_REF] Darblay | Environmental and Societal Responsibility, Internal document[END_REF][START_REF] Golbey | More than paper, our corporate social responsibility[END_REF]. Large volumes of ashes are still difficult to recover even if potential recycling routes for wastepaper sludge ash (WSA) have been investigated such as soil amendments, soils stabilization, road sublayers, partial replacement of cement in concrete industry, manufacture of plaster blends of blocks and lightweight aggregates [START_REF] Amit | Application of paper sludge ash in construction industry -a review[END_REF][START_REF] Johnson | Potential uses of waste sludge in construction Industry: a review[END_REF][START_REF] Dunster | Paper sludge and paper sludge ash in Portland cement manufacture, MinRes case study[END_REF][START_REF] Ahmad | Study of Concrete Involving Use of Waste Paper Sludge Ash as Partial Replacement of Cement[END_REF][START_REF] Vashistha | Valorization of paper mill lime sludge via application in building construction materials: A review[END_REF][START_REF] Shakir | Development of bricks from waste material: a review paper[END_REF][START_REF] Bui | Influence of industrial by-products and waste paper sludge ash on properties of recycled aggregate concrete[END_REF].

2 Sometimes paper sludge is used after specific treatment as an absorbent material such as the absorption of pollutants in the case of ammonium (NH 4+ ) present in municipal, industrial, and agricultural wastewaters and leachate [START_REF] Nguyen | Paper waste sludge-derived hydrochar modified by iron (III) chloride for enhancement of ammonium adsorption: An adsorption mechanism study[END_REF]. Till now a part of WSA continues to be disposed-off or landfilled. The reuse of WSA in an economical and environmentally sustainable manner for manufacturing alternative materials is always a challenge. The environmental quality of paper sludge and WSA have been investigated by Boni et al., [START_REF] Boni | Environmental quality of primary paper sludge[END_REF] and Zmamou [START_REF] Zmamou | Eco-conception de nouveaux agromatériaux à partir de cendres de chaudière biomasse. Relation structures-propriétés[END_REF] respectively, demonstrating the non-hazardous nature for the environment in terms of heavy metal release. Based on these environmental considerations and due to the chemical properties of the fly ash, WSA is considered as an alternative source of sustainable waste material in the construction industry. In addition, it is estimated that the annual production of OPC will increase by approximately 50%, starting from the year 2017 to the end of 2050. Meanwhile, the manufacturing of 1 ton of OPC is estimated to release approximately 1 ton of carbon dioxide (CO2) [START_REF] Monteiro | Towards sustainable concrete[END_REF]. So, using of other alternative materials like WSA constitutes an environmental and economic solution.

Most research work has shown that there are two ways of recovering WSAs, either by adding them to Ordinary Portland Cement (OPC) or by partially substituting cement in mortars or concrete [START_REF] Monosi | Reuse of Paper Mill Ash in Plaster Blends. The Open Waste[END_REF][START_REF] Buruberri | Preparation of clinker from paper pulp industry wastes[END_REF][START_REF] Elouazzani | Caractérisation physico-chimique et valorisation en bâtiment et travaux publics des cendres issues de l'incinération des boues de papeterie[END_REF][START_REF] Martínez-Lage | Concretes and mortars with waste paper industry: Biomass ash and Dregs[END_REF][START_REF] Rozineide | Geopolymer syntetized from bottom coal ash and calcined paper sludge[END_REF][START_REF] Shiqin | Properties of wastepaper sludge in geopolymer mortars for masonry applications[END_REF][START_REF] Simão | Wastecontaining clinkers: Valorization of alternative mineral sources from pulp and papermills[END_REF][START_REF] Spathi | A simple method for preparing super-hydrophobic powder from paper sludge ash[END_REF][START_REF] Wong | Hydrophobic concrete using waste paper sludge ash[END_REF][START_REF] Dailly | Valorisation de cendres volantes de papeterie en technique routière[END_REF][START_REF] Norazlan | Clay soil stabilized using Waste Paper Sludge Ash (WPSA) Mixtures[END_REF][START_REF] Segui | Elaboration de liants hydrauliques routiers à base de pouzzolane naturelle ou cendre volante de papeterie[END_REF][START_REF] Vegas | Freeze-thaw resistance of blended cements containing calcined paper sludge[END_REF][START_REF] Fava | Paper mill sludge ash as a supplementary cementitious material[END_REF][START_REF] Sharipudin | Influence of waste paper sludge ash (WPSA) and fine recycled concrete aggregate (FRCA) on the compressive strength characteristic of foamed concrete[END_REF][START_REF] Ahmad | Study of concrete involving use of waste paper sludge ash as partial replacement of cement[END_REF][START_REF] Ferrándiz-Mas | Lightweight mortars containing expanded polystyrene and paper sludge ash[END_REF][START_REF] Frias | Paper sludge, an environmentally sound alternative source of MK-based cementitious materials-A review[END_REF][START_REF] Kumar | Performance of concrete using paper sludge ash and foundry sand[END_REF]. In particular, WSAs are used in mortars for masonry to support green technology as carbon dioxide emissions can be reduced since lower cement production is involved [START_REF] Sani | Properties of Waste Paper Sludge Ash (WPSA) as cement replacement in mortar to support green technology material[END_REF]. Concerning the recent above-mentioned studies, a maximum amount of WSA is reused ranging from 50% to 100%, with very high cement addition levels till 50%. Usually a microstructure analysis is also coupled with environmental and mechanical properties during the implementation of such studies.

Nevertheless, the main technical obstacles to the WSAs recovery are the presence of free lime which by excess causes problems of swelling and their activation. Very few studies focus on the activation of WSAs [START_REF] Seifi | Mechanical performance of a dry mortar without cement, based on paper fly ash and blast furnace slag[END_REF] even though this technique is widely used for coal fly ash and in the development of geopolymers [START_REF] Amran | Fly ash-based eco-friendly geopolymer concrete: A critical review of the long-term durability properties[END_REF]. In the present study the choice not using the activators usual for fly ash i.e. NaOH, KOH, and Na2SiO3, is to reduce the cost of the WSA-based recovered product, to avoid handling chemicals and to use first traditional and commercial binders such as cement, lime and calcined kaolin. This last additive makes it possible to increase the compressive strength. Usually this also possible by incorporation of a coarser grain size corrector as a sand and if possible, a waste sand to preserve natural resources [START_REF] Manoharan | Engineering properties of concrete with partial utilization of used foundry sand[END_REF][START_REF] Manoharan | Use of waste foundry sand as a partial replacement to produce green concrete: Mechanical properties, durability attributes and its economical assessment[END_REF]. As observed by de la Villa et al., [START_REF] De La Villa | Mineralogical and morphological changes of calcined paper sludge at different temperatures and retention in furnace[END_REF], the WSA obtained after incineration is combined with reactive silica, alumina and lime, where the chemical composition remains similar as that of Portland cement components. Bai et al., [START_REF] Bai | Compressive strength and hydration of wastepaper sludge ash-ground granulated blastfurnace slag[END_REF] observed that the presence of CaO in WSA has both negative and positive effects for the use of WSA as a hydraulic binder for the hydration post-setting.

However, for practical applications, WSA ash needs further investigation to become attractive technically, economically and eco-friendly and to be rendered as more market appealing. Following the European directive [44], the current study focuses on elimination of WSA waste and recycling at a possible large scale. Depending on its physical and chemical properties, WSA is considered as a hydraulic binder in different mixtures in which WSA is the major component, whilst additives are added to control the hydration post setting effect [START_REF] Bai | Compressive strength and hydration of wastepaper sludge ash-ground granulated blastfurnace slag[END_REF] and to enhance compressive strength. The present study was designed to reduce the amount of WSA waste in the paper industry by investigating new recycling routes and also reducing the use of natural resources. The main objective was to evaluate the feasibility and the implementation of a high volume of wastepaper sludge ash in mixtures blended with cement and/or lime, or with calcined kaolin. Then, the additives influence on WSA based mixtures i.e. cement and calcined kaolin, has been investigated through the unconfined compressive strength (UCS), the density and the morphology. Considering their mechanical properties, possible WSA recycling routes could be proposed as for addition of cement with a weight ratio of 95/5 suitable in nonstructural materials and for the addition of only 5% of calcined kaolin enhancing the UCS, construction materials may be considered.

MATERIALS AND EXPERIMENTAL TESTING 2.1 Raw materials

The WSA was provided directly by the French company UPM Chappelle Darblay, located in Grand-Couronne, near Rouen harbor (France). To burn wastepaper and other inputs, the fluidized bed technology was applied as recommended by Directive 2000/76/EC [START_REF]European council, Directive on Incineration of Waste[END_REF]. So, the sludge remains in the combustion zone for a few seconds at 850 °C, the flue gas is filtered and the WSA is recovered. A quantity of 60 000 tons/year of WSA is produced and stored in silos. The WSA recycling consists of mixtures of WSA and mineral additives without any treatment. WSA based mixtures are composed either with cement (C) or with calcined kaolin (CK). In both mixtures, lime had also been added. Some reference mixtures with only WSA as a component have been made to investigate WSA binder ability and WSA efficiency in different mixtures tested. WSA dry material was provided by UPM paper mill (Rouen, France) which uses 100% recycled paper as the raw material [START_REF] Darblay | Environmental and Societal Responsibility, Internal document[END_REF]. WSAs were obtained from the combustion process of de-inking sludge with wood waste. They are classified as F class for fly ash according to ASTM [START_REF] Astm C | Standard specification for coal fly ash and raw or calcined natural pozzolan for use in concrete[END_REF] and as non-hazardous waste [44].

All WSA-based mixtures proposed are composed with: -Wastepaper Sludge Ash (WSA), main component of mixture recovered as a fine powder.

-Ordinary Portland Cement (OPC), referenced as a CEM II B-M (S-LL) 32.5R, with a mean diameter D50 of 507µm. As this study is part of a sustainable development context, so the type of cement employed was of commercial origin and supplied by a local cement plant in the same region where the wastepaper sludge ash was acquired. Although, a CEMI type cement would have been preferable as cement reference, but the cement plant had only a CEMII type of cement which already contains mineral additions other than clinker.

-Commercial quicklime L, graded as 0/1.5 mm lime with a CaO percentage exceeding 93%, and a mean diameter D50 of 567 µm.

-Calcined Kaolin (CK), a commercial fine powder with a mean diameter D50 of 50 µm, -Tap water. After selecting all the constituents, a complete characterization of the mixture was carried out for its chemical, physical, and morphological properties. The wastepaper sludge ash as main component in mixtures investigated is more detailed and only partial characterization is reported for mixtures additives i.e. cement (C), lime (L), calcined kaolin (CK).

Specimen preparation and mixture

The sample preparation consists of 3 steps: -Mixture preparation using a laboratory mixer: Its first involved weighing various constituents of the mixture and pouring them into the mixer. Afterwards, these were dry homogenized. Water was added carefully in order to control the consistency of the mixture.

-Compaction and molding of samples: In previous studies, three methods of compaction for fine soils mixed with binders have been tested and compared by Liu [START_REF] Liu | Traitement des sédiments et des sols fins[END_REF]. These methods consisted of coring at the desired sample shape, dynamical compaction as the standard Proctor procedure, manual compaction and picketing. The last method was developed by Duan [START_REF] Duan | Caractérisation, stabilisation et solidification de sédiments fins marins[END_REF], considering the following points (i) very near compressive strength obtained for samples of same mixture, (ii) easier to prepare and repeatable, (iii) time saving for preparing a specimen. It has been concluded that this is the best method. This method of compaction was selected as it was also assumed to be more representative for implementing on road layers so was employed in present study.

-Air curing period till testing at 7, 14 or 28 days: After demolding, the samples were stored and cured at laboratory temperature, 20 °C ±2 °C. The specimens used are cylindrical and have a slenderness ratio of 2, in accordance with the standard NF P 98-230-2, 1993 [START_REF]Essais relatifs aux chaussées -Préparation des matériaux traités aux liants hydrauliques ou non traités -Partie 2 : fabrication des éprouvettes de sables ou de sols fins par compression statique[END_REF]. The dimensions of mold specimens are 34*68 mm (diameter* height). Three samples are tested as required by standards for any mixture. As said above, in the present study, two hydraulic mineral matrices were investigated: (i) WSA-Cement+/-Lime and (ii) WSA-Calcined Kaolin+/-Lime. The cement or lime additions in the first series of mixes were 0, 5 or 10 wt%. The different mixes and their references are presented in table 1. For the second series of mixes, calcined kaolin varied from 5 to 40wt% and a constant of 30wt% of lime was added. Compositions and references are shown in table 2. Ratios of Water/Binder are also indicated in tables 1 and 2.

Experimental testing

The ratio Water/Binder (W/B) of each mixture was determined in order to keep constant workability of mixtures. The unconfined compressive strength (UCS) tests were performed on cylindrical samples for all mixtures at different dates i.e. [START_REF] Amit | Application of paper sludge ash in construction industry -a review[END_REF][START_REF] Nguyen | Paper waste sludge-derived hydrochar modified by iron (III) chloride for enhancement of ammonium adsorption: An adsorption mechanism study[END_REF][START_REF] Norazlan | Clay soil stabilized using Waste Paper Sludge Ash (WPSA) Mixtures[END_REF]

WSA CHARACTERIZATION 3.1 Chemical composition

The chemical composition of WSA powder was determined by X-Ray fluorescence (XRF) analysis. X-ray fluorescence spectroscopy is a non-destructive method. The WSA powder was compacted to obtain pellets. Mapping of a surface of WSA-pellet has been performed to obtain the chemical elements present in WSA. The source used is Rhodium (Rh) with X-ray beam size of 30 μm. Conversion factor is used for various elements to obtain oxides content. The oxide composition of the wastepaper sludge ash used for the mixtures is shown in figure 1. Wastepaper sludge ash is mainly composed of calcium oxide (CaO), silica (SiO2) and alumina (Al2O3). Other constituents are considered as minor ones (MgO, SO3, K2O, TiO2, MnO, P2O5). According to the presence of oxides and their amount, WSA can be compared to the cement (hydraulic binder) or to the fly ash (pozzolanic binder). This comparison allows investigation of the potential reuse of WSA as a binder [START_REF] Levacher | Wastepaper sludge ash reuse: binder or additive? 13 th Geo-Environmental Engineering[END_REF]. WSA is very rich in calcium oxide (>50%). According to the chemical composition obtained, the nature of fly ash is silica-calcareous type. The total percentage of three major oxides (CaO, SiO2, Al2O3) accounts for nearly about 92% as shown in figure 1. The calcination of wastepaper sludge ash (WSA) at 480 °C during 6 hours provides a very low organic matter content (1.4%), that corresponds to the UPM Company commercial reference product given as Calcichap as inorganic fly ash [START_REF] Zmamou | Eco-conception de nouveaux agromatériaux à partir de cendres de chaudière biomasse. Relation structures-propriétés[END_REF].

WSA grain size distribution and morphology

In accordance with the environmental laws, French recycled paper industries must continuously control WSA characteristics along their production (chemical composition, grain size, etc.). When a low variation in these parameters is observed, it is considered as negligible. Figure 3 demonstrates the grain size distribution obtained by two laboratories (Lab U i.e Unilasalle, April 2013 and Lab M. i.e. M2C, May 2013). The two-particle size distributions were determined by laser granulometry at two different dates. Figure 3 clearly shows that WSA distributions are similar with a mean diameter of wastepaper sludge ash estimated to be 290 µm. About 80% of ash has a fine particle size below 600 µm. Furthermore, a consistent WSA production is confirmed. This consistency is considered very important in a future industrial process for manufacturing WSA-based materials. Some WSA grain size properties obtained according to the French standards are given in table 3. But physical characterization includes morphology, ignition loss, actual density, Blaine specific surface area, and particle morphology analysis (granulo-morphology). These parameters were chosen because they have a significant impact on the reactivity of WSA in cementitious matrices. These parameters they play a role water demand, so in the workability of matrices. To summary the main physical properties of WSA are listed in table 3.

Parameters

Solid particles density (g/cm 3 ) 2.87 [START_REF] Seifi | Mechanical performance of a dry mortar without cement, based on paper fly ash and blast furnace slag[END_REF] BET surface area (m 2 /g) 2.12 [START_REF] Seifi | Mechanical performance of a dry mortar without cement, based on paper fly ash and blast furnace slag[END_REF] Bulk density (t/m 3 ) 0.923

Particle size D50 (μm) 290 µm

Coarse grain (>2000 µm) (%) 0

Medium grain (80-2000 µm) % 78

Fine grain (2-80 µm) % 21

Very fine grain (<2 µm) % 1

Relative hymidity HR (%) 0.1

LOI (%) 1.4
Color Grey

Oder Oderless

Table 3: Main physical properties of wastepaper sludge ash.

The specific surface of WSA was evaluated by the BET (Brunauer-Emmett-Teller) method [START_REF] Seifi | Mechanical performance of a dry mortar without cement, based on paper fly ash and blast furnace slag[END_REF]. WSA has a significantly higher specific surface, which should imply a very high water demand and, this has been observed during the preparation of mixtures. WSA bulk density is less than 1 t.m -3 compared to constituent values for mixtures used as binders (2100-3100 kg.m -3 ). Monosi and al. [START_REF] Monosi | Reuse of Paper Mill Ash in Plaster Blends. The Open Waste[END_REF], observed that the bulk density of the paper ash is equal to 1200 kg.m -3 which is lighter than ordinary sand (that predictably ranges from 2500 to 2600 kg.m -3 ) and binders (2100-3100 kg.m -3 ).

The solid particles density of WSA, measured with a helium pycnometer, shows that the value varies between 2500 and 2900 kg.m -3 as determined by Davidenko, [START_REF] Davidenko | Hydratation d'un système cimentaire binaire contenant des cendres volantes de biomasse[END_REF]. The bulk density of the WSA mixed is 0,923 t.m -3 where, the relative humidity after 24 hours in the oven at 105 °C was 0.1%. All WSA was dried before mixing samples for the 2 test series. WSA grain morphology observed by scanning electron microscope (SEM) images is illustrated in figure 4. WSA exhibited grains of irregular shapes with opened or closed spheres. This explains the high capacity of water absorption of WSA. The grain size of all additions is less than 2 mm, so all mixtures have a fine granulometry while, cement and lime powders are not well graded.

MECHANICAL STRENGTH 4.1 Unconfined compressive strength (UCS)

UCS maximal average values obtained for 3 samples at different ages for both WSA Cement-based mixtures and WSA-Calcined Kaolin mixtures are illustrated below in figures 6 and 7, respectively. The water demand depends upon mixtures considered as indicated by the Water/Binder (W/B) ratio values. UCS resistance ranges from 1 to 9 MPa considering all mixtures. For WSA-C-L mixtures, UCS value after 28 days was approximately 2.5 MPa with only 5% and 10% of cement. But UCS tends to drop below 2.5 MPa with the addition of lime. It can be partly explained by the composition of WSA. WSA powder contains more than 50% of CaO, part of which is free lime. So, addition of lime is not necessary, WSA content 3.8% of free lime. Concerning the UCS results of WSA-CK mixtures, UCS resistance relies on the percentage of calcined kaolin being added. Only 5% of CK gives the highest UCS value. Beyond 5%, the UCS falls down and reaches a value of 2 MPa whatever the addition level from 10 to 40% addition. This drop is observed along the curing time. An optimal CK amount value is detected around the 5%. For mixtures with calcined kaolin, it is not possible to keep the W/B ratio constant for all mixes, because CK additive has a higher capacity of water absorption. For example, for WSA-5CK mix with a W/B ratio of 0.4, the mixture is low workable. To improve the workability i.e. water demand, W/B increases but when W/B ratio is greater than > 0.4, the mixture tends to be quickly wetter. When CK level increases, water demand is adjusted as shown in figure 7 and consistency was kept constant. Cost of calcined kaolin is almost twice as compared to that of cement. Regarding intended application and considering the mechanical resistance (UCS) and the cost of various additives, the mixtures with 5% of cement or calcined kaolin are sufficient for proposing a WSA-based material for a road sublayer or construction material, respectively. Recall that a value of 1 MPa could satisfy requirements for road sublayers. Mixtures (WSA-C5 and WSA-C10) with 5% and 10% of cement respectively and W/B=0.6 have the same trend, thus achieving the similar UCS value. In order to use a minimal quantity of additives, the mixture with only 5% was chosen. These results indicate that the mechanical strength depends on the quantity of water added and the age of samples. UCS tends to increase over 28 days for the two mixtures with 5% of cement or calcined kaolin.

Figure 8 shows the effect of lime and calcined kaolin addition on mechanical strength at 28 days. As observed, lime does not affect the strength considerably, unlike calcined kaolin.

UCS-bulk density relationship

Bulk density was determined from mass and dimensions of samples before testing. UCS at different days of curing i.e. UCS for 7, 14 and 28 days is related to bulk density of material in figure 9: a) Mixtures WSA-Cement-Lime, b) WSA-CK-Lime. On the one hand, density according to every added component varies and depends on the hardening of the mixture. So UCS relies on the density of materials. We obtained two UCS ranges with the two series of mixtures being considered. The values for WSA-C-L mixtures matrix ranged from 1.5 to 3 MPa, while reached up to 9 MPa in case of WSA-CK mixtures.

CONCLUSIONS, RECOMMANDATIONS AND FUTURE INVESTIGATION

A series of UCS tests were carried out on WSA cement-based mixtures (WSA-C-L) and WSA-calcined kaolin mixtures (WSA-CK-L) that contained different cement and lime (or calcined kaolin) contents. Both cement plus lime or calcined kaolin contents as water demand W/B ratio varied to explore the optimum WSA recycling and compressive strength efficiency for different WSA mixtures. Some major conclusions were drawn as follows:

(1) UCS values of WSA reference sample i.e. 100% WSA seems to slightly decreased along the 28 days curing time nearing 2 MPa. (2) WSA cement-based mixtures show another hardening trend during the 28 days of curing. UCS slightly increases with time. A mixture with a WSA-cement mass ratio of 95/5 (minimal cement content) developed a UCS of 2.5 MPa which was the highest value at 28 days. (3) Lime addition does not affect UCS strength. This can be explained by the presence of 51% of CaO in the WSA and the presence of free lime (3.8%). ( 4) Considering WSA calcined kaolin-based mixtures with CK low additions (≤10%), UCS increases with curing time. We observed particularly with only 5% of calcined kaolin, a 9 MPa UCS value is achieved at 28 days. (5) A 5% CK addition has shown a clear different behaviour comparing to higher CK contents during hardening period. To more eco-friendlily produce materials by recycling maximum of WSA and minimising the consumption of cement or calcined kaolin, various mixes with different volumes of WSA were investigated and conclusions above mentioned. But recycling 100% WSA without any addition does not seem acceptable for any material in terms of strength. So, two types of addition were proposed: a cement and calcined kaolin, to increase the strength of WSA mixtures. The highlighted results of this study confirm that using of 5% of cement should be more suitable in nonstructural construction materials or stabilized materials as a road sublayer with adding other acceptability tests. Concerning calcined kaolin as addition, a CK dosage of 5% could provide materials for applications in building materials. It is still necessary to investigate and to optimize this dosage. The present study has revealed that the recycling of wastepaper sludge ash (WSA) as the main secondary raw material is clearly promising and possible. A more detailed research work will help to ensure better use of this waste material and for the most suitable recycling routes. Based on the results obtained in present study and suggested recommendations, future research work will concern the following: (1) Durability behavior of wastepaper sludge ash-based materials to investigate the influence of severe climate conditions (wetting/drying, freeze/thaw) on mechanical strengths. (2) Environmental behavior during the curing time by analyzing the possible presence and amounts of heavy metals. Leaching tests are recommended on WSA raw materials and on the WSA-based mixtures. Both behavior studies could be coupled. (3) Full-scale behaviour of wastepaper sludge ash materials. A full-scale road sublayer will be implemented and some elements of building materials (paving units, bricks and cinder blocks...) be manufactured. So, WSA-based materials will be investigated in situ conditions. Scale effects between laboratory-site could be analyzed and discussed with technical difficulties observed during site applications.

Figure 1 :

 1 Figure 1: Chemical composition of WSA. The chemical composition of WSA produced by UPM Chappelle Darblay in 2013, was measured and compared with different chemical compositions of WSA available in literature, as shown in figure 2. All the results of chemical composition of WSA used were obtained from the following references[13, 28-30, 43, 51-59]. In figure2, we have chosen to write the main author's name with the year of publication in order to show the variability of material according to the source and year of investigation. It is clearly observed that the composition of major oxides varies from 77% to 92%, showing overall consistency of the WSA composition in the world.

Figure 2 :

 2 Figure 2: Chemical composition of different WSA investigated around the world.3.2 WSA grain size distribution and morphologyIn accordance with the environmental laws, French recycled paper industries must continuously control WSA characteristics along their production (chemical composition, grain size, etc.). When a low variation in these parameters is observed, it is considered as negligible. Figure3demonstrates the grain size distribution obtained by two laboratories (Lab U i.e Unilasalle, April 2013 and Lab M. i.e. M2C, May 2013). The two-particle size distributions were determined by laser granulometry at two different dates. Figure3clearly shows that WSA distributions are similar with a mean diameter of wastepaper sludge ash estimated to be 290 µm. About 80% of ash has a fine particle size below 600 µm. Furthermore, a consistent WSA production is confirmed. This consistency is considered very important in a future industrial process for manufacturing WSA-based materials. Some WSA grain size properties obtained according to the French standards are given in table3. But physical characterization includes morphology, ignition loss, actual density, Blaine specific surface area, and particle morphology analysis (granulo-morphology). These parameters were chosen because they have a significant impact on the reactivity of WSA in cementitious matrices. These parameters they play a role water demand, so in the workability of matrices. To summary the main physical properties of WSA are listed in table3.

Figure 3 :

 3 Figure 3: Typical WSA grain size distributions.

Figure 4 :

 4 Figure 4: WSA grain morphology by SEM images.3.3 Comparative grain size distribution of mixture componentsFigure5presents the grain size distribution (GSD) of mixed components, also determined by laser granulometry.

Figure 5 :

 5 Figure 5: Components grain size distributions in mixtures.

Figure 6 :

 6 Figure 6: Cement and lime addition effect on UCS of WSA-based mixtures vs time.

Figure 7 :

 7 Figure 7: Calcined kaolin addition effect on UCS of WSA-based mixtures vs time.

4 Figure 8 :

 48 Figure 8: Effect of lime or calcined kaolin addition on UCS of WSA-based mixtures at 28 days.

Figure 9 :

 9 Figure 9: UCS-bulk density relation for WSA-based mixtures: a)-WSA-C-L, b)-WSA-CK

Figure 10 :

 10 Figure 10: Morphological structure of WSA-C5 and WSA-CK5 at 7 and 28 days (day=d on figures) of curing by SEM. Observations revealed the presence of various mineral phases such as portlandite and ettringite in several forms (free or oxide). SEM images clearly depict the presence of WSA spherical grains concerning the WSA-C5 mixture. It indicates the presence of non-hydrated grains of WSA in this mixture. Consequently, lower values of UCS are obtained for WSA-C5 mixture.

Table 1 :

 1 days in air curing conditions at 20 °C±2 °C. WSA based mixtures with cement.

	Mixtures	WSA 1	C 2	L 3	W/B 4
	WSA	100	0	0	0.5
	WSA-C5	95	5	0	0.6
	WSA-C10	90	10	0	0.6
	WSA-C5-L5	90	5	5	0.6
	WSA-C5-L10	85	5	10	0.6
	1 Wastepaper Sludge Ash, 2 Cement, 3 Lime, 4 Water/Binder

Table 2 :

 2 WSA based mixtures with calcined kaolin. The UCS is the main mechanical parameter in the experimental program from which two types of WSA based mixtures must be analyzed and compared.

ACKNOWLEDGMENTS

A part of this study was financially supported by French ANRT and UPM Chappelle Darblay Company grant-inaid for scientific research. The authors express their gratitude to the Glyco-Mev laboratory for SEM images (Rouen University).


Li-Anne Zhu
email: liannezhu90@gmail.com

Julie Blanc

Hélène Heckenroth
email: helene.heckenroth@ap-hm.fr

Caroline Peyronel
email: caroline.peyronel@reseauperinatmed.fr

Blanche Graesslin
email: blanche.graesslin@neoventa.com

Michèle Marcot
email: michele.marcot@reseauperinatmed.fr

Sophie Tardieu
email: sophie.tardieu@ap-hm.fr

Florence Bretelle
email: florence.bretelle@ap-hm.fr

Keywords: Fetal physiology cardiotocography training, a regional evaluation Cardiotocography, fetal physiology, training

A CTG training programme based on fetal physiology showed a significant improvement in the professionals' interpretation of CTG at short term

Introduction:

Cardiotocography (CTG) has its limits in detecting fetal acidosis and intrapartum asphyxia.

Our aim was to evaluate a CTG training programme based on fetal physiology in the Mediterranean perinatal network. Methods: Professionals from 41 maternity units of the Mediterranean network were invited to participate in a CTG masterclass based on fetal physiology in March 2019 and October 2019.

They were asked to react to three practical cases by a physiological approach before the training course (T0), one month after (T1) and six to seven months after (T2). The mean scores were compared by using a mixed model including lapse of time to evaluation, profession of participants and level of the maternity unit as fixed effects.

Results:

A total of 248 professionals from 32 maternity units finally participated in the organizational audit. By using a mixed model, we found a significant improvement of the mean score at T1=6.44/10 compared to T0=4.97/10 (p<0.0001), and a significant improvement of the mean score obtained at T2=6.17/10 compared to T0 (p<0.0001). T2 scores were not significantly different from T1 scores (p=0.143).

Continuous monitoring of the fetal heart rate (FHR) by cardiotocography (CTG) is the established reference method for fetal monitoring during labour. This tool has limits regarding screening for fetal acidosis and intrapartum asphyxia [START_REF] Clark | The limits of electronic fetal heart rate monitoring in the prevention of neonatal metabolic acidemia[END_REF]. The main differences in performance were found in the interpretation of decelerations [START_REF] Sholapurkar | Obstetrics at Decisive Crossroads Regarding Pattern-Recognition of Fetal Heart Rate Decelerations: Scientific Principles and Lessons From Memetics[END_REF], the evaluation of variability [START_REF] Shaw | Variations on fetal heart rate variability: Translational perspectives[END_REF] and in the classification of intermediate tracings [START_REF] Ayres-De-Campos | FIGO consensus guidelines on intrapartum fetal monitoring: Introduction[END_REF]. The subjectivity of this analysis was also observed when the observer was aware or not of adverse neonatal outcome [START_REF] Vejux | Guideline choice for CTG analysis influences first caesarean decision[END_REF][START_REF] Sabiani | Intra-and interobserver agreement among obstetric experts in court regarding the review of abnormal fetal heart rate tracings and obstetrical management[END_REF][START_REF] Blackwell | Interobserver and intraobserver reliability of the NICHD 3-Tier Fetal Heart Rate Interpretation System[END_REF].

According to the 2017 Cochrane review [START_REF] Alfirevic | Continuous cardiotocography (CTG) as a form of electronic fetal monitoring (EFM) for fetal assessment during labour[END_REF], in comparison with intermittent auscultation (IA), CTG was associated with a 63% increase in the rate of cesarean deliveries and with 15% more instrumental extraction but was not associated with a reduced incidence of cerebral palsy [START_REF] Clark | Temporal and demographic trends in cerebral palsy-Fact and fiction[END_REF].

In France, use of the Collège National des Gynécologues Obstétriciens Français (CNGOF) classification simplified by Carbonne et al in 2013 or the Fédération Internationale de Gynécologie et Obstétrique (FIGO) classification revised in 2015 are recommended for CTG analysis. These "3 or 5 tier" classifications are not used by all healthcare professionals and their interpretation can vary. A CTG tracing that accounts for fetal physiology may reduce this variability and respect fetal health conditions while reducing indications for emergency fetal extraction [START_REF] Pinas | Continuous cardiotocography during labour: Analysis, classification and management[END_REF][START_REF] Ugwumadu | Are we (mis)guided by current guidelines on intrapartum fetal heart rate monitoring? Case for a more physiological approach to interpretation[END_REF].

Several physiologists defend the view that intrapartum foetal surveillance should be approached from a physiological standpoint which also consists of accurately identifying fetuses at risk of intrapartum compromise, rather than just focusing on the morphological appearances of the FHR tracings [START_REF] Doret | Bases physiologiques de l'analyse du rythme cardiaque foetal au cours du travail[END_REF][START_REF] Garabedian | Understanding fetal physiology and second line monitoring during labor[END_REF][START_REF] Turner | The physiology of intrapartum fetal compromise at term[END_REF][START_REF] Lear | Understanding Fetal Heart Rate Patterns That May Predict Antenatal and Intrapartum Neural Injury[END_REF][START_REF] Lear | Peripheral chemoreflex control of fetal heart rate decelerations overwhelms the baroreflex during brief umbilical cord occlusions in fetal sheep[END_REF]. These considerations however, have yet to be validated to replace or at least be complementary to the CNGOF classification.

It is necessary to consider CTG interpretation as an essential skill in intrapartum health care [START_REF] Ugwumadu | Time to optimise and enforce training in interpretation of intrapartum cardiotocograph[END_REF]. A literary review has already shown the importance of training in CTG analysis and its positive impact in clinical practice [START_REF] Pehrson | Evaluation and impact of cardiotocography training programmes: a systematic review: Evaluation and impact of CTG training programmes[END_REF], however there is no initial standardized and generalized training on a regional, nor even an international level. On-site training has been proposed since 2015 in the Auvergne-Rhône-Alpes perinatal network and its evaluation has shown an improvement in healthcare professionals' knowledge of CTG [START_REF] Froc | Formation à l'analyse du rythme cardiaque foetal : évaluation d'un programme d'enseignement in situ au sein du réseau périnatal Auvergne-Rhône-Alpes[END_REF]. Likewise, in the Aquitaine area there are FHR monitoring workshops with a "training network" accreditation that enables to expand them to the majority of public or private maternity units in that area [START_REF] Secourgeon | L'enregistrement du rythme cardiaque foetal et la gestion des événements indésirables graves : pourquoi et comment élaborer un programme de formation des cliniciens ?[END_REF].

With the aim of harmonizing this practice, we decided to evaluate a CTG teaching programme within the Provence-Alpes-Côte d'Azur, Corsica and Monaco perinatal network.

Based on literature and the examples above, we hypothesized that knowledge would be improved after a CTG teaching course including fetal physiology, even some time later. The primary objective of our study was to evaluate this training by comparing the knowledge of healthcare professionals before (T0) and a short (T1) or long (T2) term after the course.

Secondary objectives were to review the current practices concerning fetal monitoring in the 41 maternity units belonging to the Mediterranean Network (Réseau Méditerranée). We also wanted to assess the participants' satisfaction with regards to the course.

Material and Methods: 2.1 Teaching course on CTG analysis and evaluation of knowledge prior to the course (T0):

The Mediterranean Network proposed a teaching course on CTG interpretation including fetal physiology. It took place in Marseille and Nice with two sessions in March 2019 and two others in October 2019. The course was in the form of a masterclass led by a midwife specialized in CTG and trained in fetal physiology [START_REF] Chandraharan | Intrapartum care: An urgent need to question historical practices and 'non-evidence'-based, illogical foetal monitoring guidelines to avoid patient harm[END_REF][START_REF] Robertson | Each baby counts in 2018 -lessons learned and future directions[END_REF].

A satisfaction questionnaire was handed out to all of the participants in order to evaluate Kirkpatrick Level 1 [START_REF] Bates | A critical analysis of evaluation practice: the Kirkpatrick model and the principle of beneficence[END_REF].

The following subjects were treated: -Physiology of FHR regulation during labour -Singularity of the mother-fetus duo -Sleep/wake cycles and variability -Interpretation of decelerations -Presentation of types of hypoxia (acute, sub-acute, chronic, evolving) For the primary objective, participants were asked to fill in a computerized organizational questionnaire on CTG before the course and respond to clinical cases on a computerized multi-choice questionnaire:

-prior to the course (T0) -short term (T1: in the month following the course) -long term (T2: 6-7 months after the course)

Clinical cases:

Actual clinical cases were transformed into progressive files with about ten questions per file.

The first case illustrated chronic hypoxia on a vascular background; the second, sub-acute hypoxia due to inappropriate use of oxytocin, the same as in the third case illustrating evolving hypoxia finally leading to bradycardia in a low-risk patient. They were reviewed and validated by the course instructor. Participants had access to information concerning the patient's medical history, parity, gestational age, pregnancy, data from the last ultrasound scan and the onset of labour. All of the CTG data, from the entrance exam to the expulsion tracing, were available as well as information concerning the progress of labour, amniotic fluid characteristics and monitor readings.

The participants had to give their answers in a computerized multi-choice questionnaire during labour progress where they were asked to propose or criticize an intervention (no intervention, corrective action, second-line tests, imminent birth) and to answer questions on fetal physiology.

Neonatal outcome was hidden from the participants so as not to influence their answers.

The last questions on the cases asked for a prediction of pH at birth and in some cases the APGAR score.

Participants were given a detailed correction with the neonatal outcome after T2.

Data collection:

In order to study the participants' knowledge in a reproducible way, the same clinical cases were studied at T0, T1 and T2. To preserve anonymity while respecting the study times, participants gave the first three letters of their first and last names. To reduce the numbers of people lost to follow-up, reminder emails were sent every week, after one month for the shortterm evaluation, and after 6-7 months for the long-term evaluation. Clinical cases were sent at 7 months for the October training course due to the COVID-19 pandemic. Each participant was given a score out of 42 (/12 for the first case, /15 for the second and last cases). Some questions were weighted (x2) when treating an essential point of the course and others gave negative points (-1) when the action or the non-action undertaken by the professional was particularly at risk for the fetus. Scores were then given out of 10 for legibility.

Statistical analysis:

Statistical analysis was performed using SPSS v20 software and SAS software for the mixed model.

Concerning the organizational part, descriptive analysis was performed on all of the collected variables in order to describe the profile of the participants, the maternity units and professional practices. Quantitative variables were expressed as average and standard deviation, median, minimum and maximum. Categorical variables were expressed as numbers or percentages. Correlation between different variables was tested with Chi-square tests.

Results were compared according to the level of maternity unit. Threshold for significance was set at 5% for all tests.

Concerning the clinical case part, an average score out of 10 was given for each of the 3 clinical cases, as well as an average total score (out of 10). The 95% Confidence Interval was calculated for each of these scores.

Mixed effects models were performed to analyze repeated measures and to manage unbalanced design or incomplete data.

Fixed effects were as follows: time of evaluation (T0, T1, T2), type of profession (midwife, obstetrician-gynaecologist), type of institute (level I, II, III), time of evaluation-by-type of profession interaction, time of evaluation-by-type of institute interaction, and the random effect was the subject. Mixed models were used with the restricted maximum likelihood estimate method and Satterthwaite degrees of freedom approximation. Least square means were compared between levels using Tukey-Kramer method. The level of significance was set at a P value of 0.05. Statistical analysis was performed using SAS Version 9.4 (SAS Institute, Cary, NC). Items are detailed in Table 1. The majority of participants was confronted with CTG analysis one or several times per week on shift. The classification the most often used was that of the CNGOF modified by Carbonne in 2013 [START_REF] Carbonne | Classification CNGOF du rythme cardiaque foetal : obstétriciens et sages-femmes au tableau ![END_REF] followed by the FIGO classification [START_REF] Robertson | Each baby counts in 2018 -lessons learned and future directions[END_REF].

Approximately one third of participants used an approach including fetal physiology. Among the 133 professionals out of 248 who declared to have had training, this was mainly occasional and took place less than once a year in 58% of cases. Among the 115 professionals who declared to have had no training, 98% considered the course useful. Intermittent auscultation was reported in slightly over half of the centres, all levels combined. Data are presented as n(%)

Clinical case results:

236 professionals participated at T0, 107 participated at T1 and 73 participated at T2. (Table 2)

There was a significant increase in the average score obtained at T1 compared to that of T0 for the different cases and for the total scores, with an average T1 score of 6.44/10 versus an average T0 score of 4.97/10 (p<0.001).

There was also a significant increase in T2 scores compared to T0 scores, with an average T2 score of 6.17/10 (p<0.001).

T2 scores were not significantly different from T1 scores (p=0.143). (Figure 1) Type of maternity unit effect and type of profession effect were not significant for all scores, except a tendency for case 3 where obstetrician-gynaecologists scores were higher than those of midwives 7.2/10 [6.9 ; 7.5] vs 6.8/10 [6.7 ; 7.0] respectively (p=0.064). "time of evaluation", "type of institute", "type of profession", and their interactions with time of evaluation. The satisfaction questionnaire was handed out immediately after the teaching course to the 260 people signed up. In March the course was given a grade of 9.8/10 for usefulness, and in October it got 9.8/10 for usefulness and 9.8/10 for the teaching method.

Discussion:

Our study found a significant increase in the average score obtained after the teaching course compared to pre-teaching scores. This concerned short-term post-teaching scores and applied to all of the different cases as well as to total scores. Long-term scores were not significantly higher than short-term scores but the results were stable, indicating the necessity to consolidate knowledge.

These results confirm those already published. One of the originalities of our study was that we chose progressive clinical cases to evaluate performance, because real-life situations seemed to be better than single choice questions about the teaching course. This evaluation was inspired by the e.RCF website from Lille University, that was proved to be useful in the study by Demailly et al [START_REF] Coletta | The 5-tier system of assessing fetal heart rate tracings is superior to the 3-tier system in identifying fetal acidemia[END_REF]. Our study was also original because the training programme used a physiological approach.

In a literary review, Pehrson et al [START_REF] Pehrson | Evaluation and impact of cardiotocography training programmes: a systematic review: Evaluation and impact of CTG training programmes[END_REF] found that theoretical knowledge was retained 6 or 7 months after CTG training and that repetitive testing led to a marked improvement in performance. After a 1997 survey on perinatal deaths in England, it was recommended that CTG knowledge of healthcare professionals should be tested every 6 months.

Froc et al [START_REF] Froc | Formation à l'analyse du rythme cardiaque foetal : évaluation d'un programme d'enseignement in situ au sein du réseau périnatal Auvergne-Rhône-Alpes[END_REF] also showed the interest of CTG analysis training in improving short-term and long-term knowledge in the Auvergne-Rhône-Alpes perinatal network. Their evaluation used a single choice questionnaire filled in before (T0) and immediately after (T1) theory training in maternity units in the form of an "outreach visit". Long-term evaluation took place over a 4-year period via "e-Learning". Froc et al observed a significant decrease in T2 scores compared to T1 showing once again the importance of repeated training.

We first could discuss that the knowledge improvement observed might be the effect of any CTG training programme. Our study could not confirm the superiority of this programme based on fetal physiology versus another programme.

Quite predictably, the highest rate of participation was at T0 and decreased over time (236 participants at T0, 107 at T1 and 73 at T2). This decrease may be explained by the fact that the correction was not given immediately, the tracings were not easy to scroll through, and it took time to fill in the clinical cases. There is, therefore, a selection bias, as the participants who answered all three times were probably the most motivated. Nevertheless, our study permitted us to collect exhaustive data representative of the network, even if the participants were mostly midwives (80%) and healthcare professionals mainly from the public sector.

Even if the neonatal outcome remained hidden until T2, there may also be a memorization bias since there were only three practical cases.

Our study provides an overview of the situation in the Mediterranean Network in order to target its actions and respond better to practitioners' expectations. Despite the biases mentioned above, we think that one of the important roles of the network is to continue to harmonize professional practices. We observed inequalities in care organization and access to education within the perinatal network. CTG training was significantly more important in level II and level III maternity units compared to level I. Half of the participants declared that this was their first teaching course on CTG, and the majority of the other half declared to have only received very occasional training. This mainly took place during service meetings and was mostly in level II and III maternity units, which also correlated with the number of obstetrical staff members reported. They were reported to be present daily in less than half of the maternity units, all units combined, and present weekly in just over a third of them. We consider that this needs to be improved. Care networks play an essential part in the definition of protocols and their dispersion [START_REF] Secourgeon | L'enregistrement du rythme cardiaque foetal et la gestion des événements indésirables graves : pourquoi et comment élaborer un programme de formation des cliniciens ?[END_REF] but their impact is sometimes limited by the motivation of the healthcare workers, geographical location (9 maternity units did not take part in the training programme, 4 of which were in the Vaucluse area) or financial cost. On the contrary to the study by Froc et al. in which type II maternity unit scores were better than type I scores, we found no significant differences between the types of unit. We were not able to compare the private and public sectors due to insufficient numbers.

Recent papers mainly state [START_REF] Pehrson | Evaluation and impact of cardiotocography training programmes: a systematic review: Evaluation and impact of CTG training programmes[END_REF] that it is important to invest in a teaching policy that would motivate healthcare workers to make improvements in their practice [START_REF] Demailly | Évaluation d'un programme d'apprentissage en ligne de l'analyse du rythme cardiaque foetal[END_REF], some going as far as suggesting compulsory knowledge tests [START_REF] Ugwumadu | Time to optimise and enforce training in interpretation of intrapartum cardiotocograph[END_REF]. Young et al. showed that the main causes for intrapartum mortality were a delay in responding to recognized CTG anomalies or failure to identify them [START_REF] Luthander | Results from the National Perinatal Patient Safety Program in Sweden: the challenge of evaluation[END_REF]. These examples show that human factors are involved in adverse fetal outcomes, they are the cause for variability in the interpretation of CTG and must be limited.

Education is one of the levers for reducing "improvisation" in healthcare. It demands investment such as programmes for the prevention of serious adverse incidents, help in staff communication and the development of medical technology.

In order to durably anchor knowledge into clinical practices, recommendations need to be simple and reproducible, this is why the simplified 2013 version of the CNGOF classification combined with a proposition of decision tree algorithms appeared to be a real solution.

However, in a study by Cheurfa et al [START_REF] Young | Reducing risk by improving standards of intrapartum fetal care[END_REF] the diagnostic value of a coloured table simplified by Carbonne remained limited in predicting acidosis (AUC <0.7) even though it made CTG interpretation easier. One of the limitations of "3 or 5 tier" standard recommendations possibly resides in the fact that they rely on the recognition of "patterns" for which our analysis is mainly descriptive. The identification of the different types of hypoxia, via a better comprehension of physiological processes at the origin of changes in CTG, is a method of analysis which would probably allow an optimization in the use of this monitoring tool [START_REF] Cheurfa | Évaluation de la forme simplifiée de la classification du rythme cardiaque foetal proposée dans le cadre des recommandations pour la pratique clinique « surveillance du travail[END_REF].

The diagnostic performance of this type of approach needs to be assessed, with objective markers used in current practice to measure the clinical impact before and after a generalized teaching programme including fetal physiology (Kirkpatrick levels 3 and 4). Indeed, no study has yet shown a significant impact on neonatal outcomes by using a more physiological interpretation of CTG. Here we studied Kirkpatrick level 1 which gave a positive feedback for the training course.

A collaboration between perinatal networks could be the answer to help consolidate best practices, thanks to sharing experiences and acting in compliance with mortality-morbidity reviews. Then training on fetal physiology could be organized in each maternity unit by professionals to relay knowledge and consolidate unity within the teams (Safety Attitude Questionnaire). As in the United Kingdom and in other medical fields, trainee and experienced professionals could be offered standardized education to maintain their CTG knowledge, at a rhythm that remains to be defined. In any case, access to continuing medical education should be made easier as it helps guarantee patient safety.

Conclusion:

A CTG training course based on fetal physiology was associated with a significant improvement in knowledge at short-term and stable results at long-term. However, it is probably necessary to repeat education courses to correctly maintain and improve long-term acquisitions.

The objective of our study was not to assess the impact of CTG interpretation via an approach involving fetal physiology on newborn and maternal health, and therefore it needs to be evaluated in current practice using objective criteria. It would be interesting to assess if it reduces the use of second line exams such as STAN or fetal scalp blood sample, operative deliveries and the rate of umbilical cord artery pH < 7.

Our study backs our belief that continuing medical education and investment in a solid health policy are the means of reinforcing the field of global skills connected with care and safety in the delivery room.

  Among the 260 healthcare professionals originally signed up for the training course, the audit finally concerned 248 professionals including 198 midwives and 50 obstetriciangynaecologists. These professionals came from 32 maternity units (13 level I, 16 level II and 3 level III maternity units). There were 22 public facilities and 10 private clinics. Nine maternity units were not represented, giving a response rate of 78%. All of the centres combined, 85 professionals attended the March course and 163 professionals attended the October course.

[ 5 .

 5 88 ; 6.41] T0 < T1 (p<0.001) T0 < T2 (p<0.001) T1 > T2 (p=0.143) Data are mean scores and 95% confidence interval. P-value adjusted from mixed model included fixed effects:

Figure 1 :

 1 Figure 1: Variation of mean scores for the clinical case results at different times T0, T1 and T2 for each case and total score

2.2 Computerized Collected data:

  under what form and how regularly, and if they knew anything about fetal physiology. The questionnaire gave the type of institution, whether public or private, shifts on site or on call, access to which second-line tests, whether there was obstetric staff and at what frequency.

	2.2.1 Organizational CTG audit:
	The organizational audit provided us with the healthcare professional's profile (age, gender,
	profession: trainee or registered midwife, junior doctor, public or private practitioner), amount
	of time spent in the delivery room, classification used in practice to interpret CTG, training in
	the subject,

Table 1 -

 1 Overview of the organizational audit results 211

	207
	208
	209
	210
	212
		Total	Level I	Level II	Level III	p
		(n=242)	(n=66)	(n=123)	(n=53)
	Professionals with shifts systematically on site
	Obstetrician-Gynaecologist 187 (78%)	36 (54%)	99 (81%)	53 (100%)	<0.05
	Junior Doctor 81 (34%)	1 (1%)	28 (23%)	53 (100%)	<0.05
	Intermittent auscultation	125 (52%)	42 (64%)	58 (47%)	25 (48%)	NS
	Classification for CTG	219 (90%)	56 (85%)	113 (92%)	50 (94%)	NS
	interpretation
	FIGO 2015 [4] 86 (39%)	29 (52%)	33 (29%)	24 (48%)	<0.05
	ACOG 2009 [25]	20 (9%)	3 (5%)	14 (12%)	3 (6%)	NS
	CNGOF 2007 26 (12%)	8 (14%)	12 (11%)	6 (12%)	NS
	CNGOF Carbonne 2013 [24] 129 (59%)	25 (45%)	74 (65%)	30 (56%)	<0.05
	Murphy Criteria [26] 26 (12%)	8 (14%)	14 (12%)	4 (8%)	NS
	Rosen 2004 (STAN) [27] 23 (10%)	4 (7%)	16 (14%)	3 (6%)	NS
	Thoulon [28]	9 (4%)	1 (2%)	6 (5%)	2 (4%)	NS
	FHR Coletta 2012 [29]	1	0	1	0	NS
	2 nd line tests	180 (75%)	32 (48%)	96 (78%)	53 (100%)	P<0.05
	Fetal scalp pH 88 (36%)	11 (17%)	28 (23%)	49 (92%)
	Fetal scalp lactates 127 (52%)	23 (35%)	72 (59%)	32 (60%)
	STAN	20 (8%)	2 (3%)	15 (11%)	3 (6%)
	Digital fetal scalp stimulation	19 (8%)	3 (4%)	7 (6%)	9 (17%)
	Doppler ultrasound 26 (11%)	5 (8%)	10 (8%)	11 (21%)
	Pathophysiological approach	62 (26%)	17 (26%)	28 (23%)	17 (32%)	NS
	CTG training	133 (55%)	28 (42%)	70 (57%)	35 (66%)	P<0.05
	Service meeting 62 (26%)	8 (12%)	33 (27%)	21 (40%)
	Continuous personal development 41 (17%)	9 (14%)	23 (19%)	41 (77%)
	Masterclass	18 (7%)	5 (8%)	8 (6%)	5 (9%)
	Other 24 (10%)	7 (11%)	14 (12%)	3 (6%)
	Obstetric staff presence	192 (80%)	40 (61%)	100 (82%) 53 (100%)	P<0.05
	Weekly 72 (37%)	24 (60%)	45 (45%)	3 (6%)
	Daily 81 (42%)	5 (12%)	27 (27%)	49 (92%)
	Several times per week	9 (5%)	1 (2%)	8 (8%)	0
	Monthly	15 (8%)	4 (6%)	11 (11%)	0
	Mortality and morbidity reviews	5 (3%)	2 (5%)	3 (3%)	0

Table 2 -

 2 Mean scores by time of evaluation -Mixed model T0

(n=236) T1 (n=107) T2 (n=73) p-values Time of evaluation effect Case 1 Chronic hypoxia

		2.93	5.00	4.53	T0 < T1 (p<0.001)
		[2.67 ; 3.18]	[4.57 ; 5.43]	[3.96 ; 5.11]	T0 < T2 (p<0.001)
					T1 > T2 (p=0.284)
	Case 2	5.37	6.96	6.59	T0 < T1 (p<0.0001)
	Subacute hypoxia	[5.20 ; 5.55]	[6.71 ; 7.21]	[6.26 ; 6.91]	T0 < T2 (p<0.0001) T1 > T2 (p=0.038)
	Case 3	6.56	7.23	7.40	T0 < T1 (p=0.001)
	Evolving and acute hypoxia	[6.39 ; 6.73]	[6.97 ; 7.49]	[7.07 ; 7.74]	T0 < T2 (p<0.001) T1 > T2 (p=0.660)
	Total	4.97	6.44	6.17
	Score	[4.85 ; 5.10]	[6,25 ; 6.63]


MD Julien Fessler

MD Marc Fischler
email: m.fischler@hopital-foch.com

MD Edouard Sage

MD Jonathan Ouattara

MD Antoine Roux

MD François J F Parquin

MD Charles Cerf

MD Alexandre Vallee

MD, PhD Morgan Le Guen

Fischler Fessler

Sage

Operating room extubation: A predictive factor for 1-year survival after double-lung transplantation

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Mechanical ventilation is a cornerstone of intraoperative and postoperative lung transplantation (LT) practices. Many concepts applied in LT originate from experience in anesthesia during cardiac surgery.

Historically, patients were maintained under prolonged sedation and mechanical ventilation until the morning after surgery or even longer. Progressively, the evolution of surgical and anesthetic methods allowed increasingly early extubation. Similarly, the Enhanced Recovery After Surgery (ERAS) Society suggested extubation in the intensive care unit (ICU) within 6 hours after cardiac surgery. [START_REF] Engelman | Guidelines for perioperative care in cardiac surgery: Enhanced recovery after surgery society recommendations[END_REF] This approach reduced the hospital length of stay, morbidity rate, and economic cost. [START_REF] Rajakaruna | Risk factors for and economic implications of prolonged ventilation after cardiac surgery[END_REF] Immediate extubation, i.e., extubation in the operating room (OR), was then proposed by some teams after cardiac surgery. 3 4 Some centers have applied this concept to LT, [START_REF] Westerlind | The use of continuous positive airway pressure by face mask and thoracic epidural analgesia after lung transplantation. Gothenburg Lung Transplant Group[END_REF][START_REF] Hansen | Early extubation after single-lung transplantation: analysis of the first 106 cases[END_REF][START_REF] Rocca | Is very early extubation after lung transplantation feasible?[END_REF][START_REF] Augoustides | Early tracheal extubation in adults undergoing singlelung transplantation for chronic obstructive pulmonary disease: pilot evaluation of perioperative outcome[END_REF] but this practice has remained anecdotal since then. However, our team has routinely adopted an OR extubation strategy according to the following fundamental practices: the use of short-acting drugs combined with effective analgesia, such as thoracic epidural analgesia; the avoidance of excessive fluid support; the maintenance of normothermia; and the application of systematic postoperative noninvasive ventilation. [START_REF] Myles | Early extubation after lung transplantation[END_REF] Our group published an OR extubation strategy based on data from two separate cohorts considering specific populations: cystic fibrosis patients [START_REF] Felten | Immediate postoperative extubation in bilateral lung transplantation: predictive factors and outcomes[END_REF] and emphysema or chronic obstructive pulmonary disease (COPD) patients. [START_REF] Assenzo | The feasibility of extubation in the operating room after bilateral lung transplantation in adult emphysema patients: an observational retrospective study[END_REF] The main objective of the present study was to predict the prognosis of patients extubated immediately by comparing it with the prognosis of patients extubated in the ICU. The secondary objectives were to evaluate the safety of this approach and to identify predictive factors associated with successful OR extubation.

Methods

The Institutional Review Board of the French Society for Anesthesia and Intensive Care approved the analysis of this prospectively maintained institutional anesthesia lung transplant database (CERAR N°IRB 00010254 -2019; June 29, 2019). Informed consent was obtained from all patients. The Foch Lung Transplant Group attests strict compliance with the International Society for Heart and Lung Transplantation ethics statement.

Study participants

All consecutive patients undergoing double-lung transplantation (DLT) at Foch Hospital (Suresnes, France) from January 2012 to June 2019 were included in the study. Patients undergoing multiorgan transplantation or cardiopulmonary bypass were excluded from the analysis, as were cases of retransplantation of patients initially transplanted during the study period. The remaining patients were divided into two groups: the OR extubation group and the ICU extubation group (Figure 1).

Transplant protocol

DLT was performed as two successive sequential single-LT procedures. [START_REF] Pasque | Improved technique for bilateral lung transplantation: rationale and initial clinical experience[END_REF] The surgical approach used two anterolateral thoracotomy incisions. Standardized anesthetic management has been previously described [START_REF] Fessler | Inhaled nitric oxide dependency at the end of double-lung transplantation: a boosted propensity score cohort analysis[END_REF] and is detailed in Supplementary File 4 (http://anesthesie-foch.org/protocoles-anesthesie/). Briefly, thoracic epidural analgesia and total intravenous anesthesia with propofol and remifentanil, systematic inhaled nitric oxide (iNO), and intraoperative femoral arterio-venous extracorporeal membrane oxygenation (ECMO) were applied either in cases of severe hemodynamic or respiratory failure refractory to medical treatment or as planned a priori (by the preoperative clinical staff).

OR extubation was preceded by hemodynamic and respiratory support de-escalation via a three-step weaning trial (Supplementary Figure 1). First, in patients under ECMO, a 10-minute weaning trial was performed by reducing the ECMO blood flow progressively to 1-1.5 L.min -1 under clinical and echocardiographic monitoring ("ECMO weaning test"). A positive test was defined as a stable left ventricular outflow and a PaO2/FiO2 ratio > 200. In the case of a positive weaning test, surgeons removed the ECMO cannulas.

Second, when the surgical procedure was performed without ECMO, the PaO2/FiO2 ratio was calculated at the end of surgery, and the following steps were performed:

-if the PaO2/FiO2 ratio was lower than 100 at the end of the procedure, ECMO was established before transferring the patient to the ICU; -if the PaO2/FiO2 ratio was greater than 100, an "iNO weaning test" was performed. iNO was interrupted and reintroduced in cases of a substantial decrease in the PaO2/FiO2 ratio (more than 10% diminution) or hemodynamic state worsening (a norepinephrine dose increase greater than 10%, fluid support greater than 250 mL, or a mean pulmonary artery pressure increase with right ventricle dilation on transesophageal echocardiography). In these cases, patients were transferred to the ICU under mechanical ventilation and iNO.

Third, for patients whose iNO weaning test was successful, a new PaO2/FiO2 ratio was calculated after terminating iNO therapy. OR extubation and a "non-invasive ventilation attempt" were performed if the PaO2/FiO2 ratio was greater than 300 and no hemodynamic failure and normothermia were detected.

The weaning trial was performed via a double-lumen tube, similar to elective thoracic surgery after the interruption of IV anesthetic agents. The "non-invasive ventilation attempt" consisted of a 20-minute period of non-invasive ventilation in an awake and calm patient using a face-mask and specific ventilator with inspiratory and expiratory airway pressures of 8 and 4 cmH2O, respectively, with an FiO2 = 100%, and adapted to patient comfort. If the attempt was successful, patients were then transferred to the ICU with a high-concentration oxygen face mask. Otherwise, the patients were anesthetized and reintubated with a single-lumen tube using a tube exchanger (Cook ® Airway Exchange Catheter -Extra-Firm with Soft Tip, Cook Medical Incorporated, Bloomington, IN, USA) before transfer to the ICU under mechanical ventilation.

Data handling

Data related to the donor and recipient and the intraoperative period were extracted for statistical analysis after anonymization by using the FileMaker Pro database (FileMaker Company, Santa Clara, CA, USA). This database was prospectively completed in real time during each procedure. Details regarding the data collection used for the analysis are provided in Supplemental File 2.

Primary and secondary outcomes

The main outcome was one-year mortality. The secondary outcomes were the prevalence of early reintubation after surgery, incidence of grade 3 primary graft dysfunction (PGD3) at 1, 2, and 3 days after the operation, ICU-related complications and length of stay. Finally, we looked for predictive factors of OR extubation.

Statistical analysis

Continuous variables are presented as median [interquartile range] and were compared using the independent t-test or Mann-Whitney test. Categorical variables are presented as number (%) and were compared using the chi-square test or Fisher's exact test.

Multivariable logistic regression was performed to assess the predictive determinants of OR extubation.

Factors associated with OR extubation in the univariable analyses (at a significance level of p<0.20) were selected for inclusion in the multivariable analysis. These factors corresponded to donor and recipient characteristics and intraoperative data up to implantation of the second graft; later items were not considered in this analysis, as they were part of the extubation decision.

The patient survival rate (time to death at one year) was estimated using the Kaplan-Meier estimator and compared by the log-rank test. A Cox regression model was performed to determine the association between OR extubation and the mortality rate at one year. Predictive determinants of OR extubation were selected as confounding factors for the Cox regression model. For all analyses, p<0.05 was considered statistically significant. Statistical analyses were performed using SAS software (version 9.4; SAS Institute, Cary, NC).

Results

A total of 475 patients underwent DLT at our institution during the study period. After excluding patients who did not meet the study criteria, 450 patients were included in the analysis; among them, 161 (35.8%) were extubated in the OR (Figure 1). All organs were obtained from brain-dead donors, regardless of the etiology, except 22 organs that were donated after circulatory death.

Safety of OR extubation

Four patients (2.5%) were reintubated within 24 hours: two in the OR (one case of undiagnosed residual neuromuscular blockade and one case of major agitation due to intense pain despite epidural analgesia in a patient with a past medical history of polytoxicomania) and two in the first hours after admission in the ICU (protocol violation because the PaO2/FiO2 ratio was < 300 mmHg after extubation). These patients were maintained in the OR extubation group (intention to treat analysis).

Furthermore, eight OR-extubated patients were reintubated during the first postoperative week but after the first 24 postoperative hours; three of them were reintubated because of primary graft dysfunction. Five additional patients were reintubated after one week because of septic complications and bronchial anastomotic leakage. Some cases of protocol violation were observed. Specifically, 9 patients were extubated when their PaO2/FiO2 ratio was < 200, and 48 patients were extubated when their PaO2/FiO2 ratio was 200-299.

Among the OR-extubated patients with a PaO2/FiO2 ratio < 200, 2 were reintubated (both within 24 hours); one died on day 9, and the other died thereafter. Among the OR-extubated patients with a PaO2/FiO2 ratio of 200-299, 2 were reintubated within 24 hours, and 6 were reintubated thereafter. In this last subgroup, only one patient died in the 10th month; he was reintubated on day 6.

Preoperative and intraoperative variables

Recipient and donor characteristics are illustrated in Table 1.

Intraoperative variables are illustrated in Table 2. Compared with ICU-extubated patients, OR-extubated patients experienced less bleeding and required fewer transfusions during surgery (p<0.001), had greater hemodynamic stability (less epinephrine support) (p<0.001) and required less ECMO support (p<0.001), and had a lower blood lactate level and a greater PaO2/FiO2 ratio after second graft implantation (p<0.001).

Nineteen percent of the patients who required intraoperative ECMO were extubated in the OR.

Predictive factors of OR extubation

Details of the multivariable analysis are provided in Supplemental File 3. Primary pulmonary disease (especially COPD and cystic fibrosis, p=0.002 and p=0.005, respectively), recipient body mass index (p=0.048), and the PaO2/FiO2 ratio 10 minutes after second graft implantation (p<0.001) were predictive factors for successful OR extubation (Figure 4). Receiver operating characteristic (ROC) curve analysis revealed that the model had a sensitivity of 82.2%, a specificity of 70.3%, and an accuracy of 74.2% in predicting OR extubation (area under the curve: 0.83; r 2 =0.39) (Figure 5).

Postoperative outcomes

Postoperative outcomes were generally better in the OR extubation group than in the ICU-extubation group (Table 3). In particular, compared to with ICU-extubated patients, OR-extubated patients had a significantly lower prevalence of PGD3 at 1, 2, and 3 days after the operation (p<0.001 for each time point).

Two (1.2%) patients and 17 (5.9%) patients died within the first 30 days after the operation in the OR extubation group and in the ICU extubation group (p=0.019), respectively. Eight (5.0%) patients died within the first year in the OR extubation group, and 39 (13.5%) patients died within the first year in the ICUextubation group; the one-year survival rate was significantly greater in the OR extubation group than in the ICU extubation group (log-rank; p=0.005). After adjustment for predictive factors, OR extubation was still associated with better one-year survival in the Cox regression model than ICU extubation (adjusted hazard ratio = 0.40 [0.16-0.91], p=0.028) (Figure 2). The rate of mortality at one year was similar in both groups when patients who died within the first 30 days were excluded from the analysis (log-rank test; p=0.081) (Figure 3). Five-year survival was also better in the OR extubation group than in the ICU extubation group (p=0.008) (Supplemental File 5).

Discussion

This retrospective single-center study showed that OR extubation i) was possible for nearly one-third of patients undergoing DLT; ii) was safe; and iii) was a clinical marker of a good prognosis, as the outcomes were better in these patients than in patients extubated in the ICU. Of prime importance was that our protocol did not include the preselection of potential patients for OR extubation and considered that all patients were candidates for OR extubation and that the decision was made at the end of the procedure according to all measured parameters. This was confirmed by the fact that 1 in 5 patients who received intraoperative ECMO were extubated at the end of the procedure. Finally, this possibility can be predicted within a few minutes after implantation of the second graft.

Interest in fast-track surgery has increased in cardiothoracic anesthesia practice. Cardiac surgery is the discipline in which reducing the time to extubation has been most studied. Historically, this time has decreased from routine extubation the morning after the operation to early extubation under the concomitant pressure of changes in anesthesiology methods (application of short-acting drugs, optimal analgesia, and restoring normothermia), [START_REF] Myles | A systematic review of the safety and effectiveness of fast-track cardiac anesthesia[END_REF] changes in surgical techniques (faster and less invasive techniques), [START_REF] Zubair | Updates in minimally invasive cardiac surgery for general surgeons[END_REF] and pressure on ICU staff (to reduce ventilation-related complications and economic constraints). In contrast to fears regarding outcomes, the rate of postoperative complications did not increase; [START_REF] Wong | Fast-track cardiac care for adult cardiac surgical patients[END_REF] however, the ERAS program, a patient-centered multidisciplinary strategy was required to reduce it. [START_REF] Engelman | Guidelines for perioperative care in cardiac surgery: Enhanced recovery after surgery society recommendations[END_REF] Hemmerling went further as he considered that a successful medical-surgical team should implement an immediate extubation strategy, as it is more difficult and more dangerous to perform extubation later, particularly because of the need to maintain sedation, which can have hemodynamic consequences. [START_REF] Hemmerling | Immediate extubation after cardiac surgery should be part of routine anesthesia practice for selected patients[END_REF] Regarding LT, the earliest studies involved relatively small cohorts with different indications, types of transplantation (single-LT and/or DLT, possibly combined with heart transplantation) [START_REF] Westerlind | The use of continuous positive airway pressure by face mask and thoracic epidural analgesia after lung transplantation. Gothenburg Lung Transplant Group[END_REF][START_REF] Hansen | Early extubation after single-lung transplantation: analysis of the first 106 cases[END_REF][START_REF] Rocca | Is very early extubation after lung transplantation feasible?[END_REF][START_REF] Augoustides | Early tracheal extubation in adults undergoing singlelung transplantation for chronic obstructive pulmonary disease: pilot evaluation of perioperative outcome[END_REF] and extubation times (a few hours after the procedure [START_REF] Westerlind | The use of continuous positive airway pressure by face mask and thoracic epidural analgesia after lung transplantation. Gothenburg Lung Transplant Group[END_REF] or in the OR at the end of the procedure [START_REF] Hansen | Early extubation after single-lung transplantation: analysis of the first 106 cases[END_REF][START_REF] Rocca | Is very early extubation after lung transplantation feasible?[END_REF][START_REF] Augoustides | Early tracheal extubation in adults undergoing singlelung transplantation for chronic obstructive pulmonary disease: pilot evaluation of perioperative outcome[END_REF] ). These studies proved that it was possible to extubate patients after LT with a low rate of reintubation. However, little information was provided regarding predictive factors of success or long-term follow-up. Our team showed that OR extubation was possible in nearly half of cystic fibrosis [START_REF] Felten | Immediate postoperative extubation in bilateral lung transplantation: predictive factors and outcomes[END_REF] and COPD/emphysema patients, [START_REF] Assenzo | The feasibility of extubation in the operating room after bilateral lung transplantation in adult emphysema patients: an observational retrospective study[END_REF] with few cases of reintubation. Interestingly, in both types of patients, OR extubation was associated with a simpler postoperative course with a low rate of reintubation, a lower prevalence of PGD3 and a shorter ICU length of stay than ICU extubation. In contrast, Felten et al. did not observe a difference in one-year mortality between OR-extubated and ICU-extubated patients in a cystic fibrosis cohort [START_REF] Felten | Immediate postoperative extubation in bilateral lung transplantation: predictive factors and outcomes[END_REF] , while Assenzo et al. found better one-year survival among OR-extubated patients than ICU-extubated patients in a COPD/emphysema cohort. [START_REF] Assenzo | The feasibility of extubation in the operating room after bilateral lung transplantation in adult emphysema patients: an observational retrospective study[END_REF] Similarly, among the whole cohort, we observed better one-year survival in the OR extubation group than in the ICU-extubation group. Upon deeper analysis, we found that this longterm mortality difference disappeared when one-year survival was adjusted for 30-day survival.

Consequently, OR extubation may be considered a strong surrogate supporting uneventful early followup, leading to a low rate of PGD, a low rate of ICU-related complications, and a decreased rate of mortality. Finally, this favorable outcome may also stem from the effect of a fast-track program in which all stakeholders are extensively involved to enhance recovery after surgery and reduce postoperative complications. However, since this was not a randomized control trial, causality is impossible to determine regarding the time of extubation.

The present study included our whole population of consecutive DLT patients regardless of their primary pulmonary pathology, except patients with primary pulmonary hypertension who were not treated at our center. This wide variety of patients confirmed the feasibility of OR extubation, although at a lower rate than that previously published 10 11 and with a minimal reintubation risk (2.8%). This rate could have been even lower if the protocol had been more scrupulously followed. Westerlind et al. initially pointed out the increase in the safety of extubation with the use of continuous positive airway pressure via a face mask. [START_REF] Westerlind | The use of continuous positive airway pressure by face mask and thoracic epidural analgesia after lung transplantation. Gothenburg Lung Transplant Group[END_REF][START_REF] Hansen | Early extubation after single-lung transplantation: analysis of the first 106 cases[END_REF][START_REF] Rocca | Is very early extubation after lung transplantation feasible?[END_REF][START_REF] Augoustides | Early tracheal extubation in adults undergoing singlelung transplantation for chronic obstructive pulmonary disease: pilot evaluation of perioperative outcome[END_REF] Currently, high-flow nasal cannula oxygen therapy is a sustainable alternative to reintubation in acute hypoxemic respiratory failure after LT. [START_REF] Roca | Humidified high flow nasal cannula supportive therapy improves outcomes in lung transplant recipients readmitted to the intensive care unit because of acute respiratory failure[END_REF] Our cohort analysis allowed us to identify predictive factors of OR extubation. First, primary lung diseases such as cystic fibrosis and COPD/emphysema are known to have a better early postoperative course than other pulmonary diseases. [START_REF] Hayes | The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Twenty-second pediatric lung and heart-lung transplantation report—2019; Focus theme: Donor and recipient size match[END_REF] Second, a donor body mass index above 25 kg/m 2 is an independent factor associated with PGD. [START_REF] Kuntz | Risk factors for early primary graft dysfunction after lung transplantation: a registry study[END_REF] Third, Pottecher et al. reported that the PaO2/FiO2 ratio measured just after graft reperfusion and some other variables that are difficult to measure (extravascular lung water and level of human soluble receptor for advanced glycation end products) are predictors of PGD. [START_REF] Pottecher | Increased Extravascular Lung Water and Plasma Biomarkers of Acute Lung Injury Precede Oxygenation Impairment in Primary Graft Dysfunction After Lung Transplantation[END_REF] Similarly, a trend of increased risk of PGD3 on day 3 was observed when the PaO2/FiO2 ratio was <200 at the end of the procedure, [START_REF] Fessler | Prognostic value of the PaO2 /FiO2 ratio determined at the endsurgery stage of a double-lung transplantation[END_REF] and a low PaO2/FiO2 ratio measured upon arrival to the ICU or a few hours later was associated with a similar risk. [START_REF] Prekker | Early Trends in PaO(2)/fraction of inspired oxygen ratio predict outcome in lung transplant recipients with severe primary graft dysfunction[END_REF] All these elements could lead to a more aggressive approach for nonextubated patients before discharge from the OR. In the absence of specific drug therapy that may reduce the severity of PGD, early prone positioning [START_REF] Riera | Prone positioning as a bridge to recovery from refractory hypoxaemia following lung transplantation[END_REF] or prophylactic ECMO [START_REF] Hoetzenecker | Intraoperative extracorporeal membrane oxygenation and the possibility of postoperative prolongation improve survival in bilateral lung transplantation[END_REF] is suggested. However, it must be noted that among patients with early PGD (6 hours after transplantation), complete resolution of dysfunction within 72 hours and attenuation without complete resolution within 72 hours were observed in 7% and 39% of the cases, respectively. [START_REF] Shah | Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation[END_REF] Finally, a limitation of the generalization of OR extubation could be the fact that our policy increases OR occupation by approximately one hour, sometimes during regular working hours. This is possible in our institution because the whole anesthesia team is fully dedicated to transplant patients.

Limitations of the study

First, our study was subject to all inherent limitations of any retrospective single-center analysis. However, all the data were prospectively collected from an institutional database with strict definitions. It would be interesting to randomize patients likely requiring extubation in the OR into two groups: an OR extubation group and an ICU extubation group, but it seems unethical to us to continue ventilation (and sedation) if it is not necessary. Second, our study focused exclusively on patients extubated in the OR and not on those extubated in the first 6, 12 or 24 hours post-operatively. Third, our cohort included a high proportion of patients with cystic fibrosis (52.0%) or COPD/emphysema (25.1%), a low proportion of patients with interstitial lung disease (14.0%) and an absence of patients with primary pulmonary hypertension. In addition, patients who underwent DLT under cardiopulmonary bypass were excluded because this technique carries a risk of specific complications and has become marginalized during the last decade after the development of ECMO. Fourth, we could not obtain data on all potential variables, such as preoperative frailty assessment results, to compare groups and better understand the differences in prognoses. Finally, in this study, we present unique practices, especially thoracic epidural analgesia combined with total intravenous anesthesia, and a three-step weaning trial at the end of surgery (ECMO systematic withdrawal, iNO withdrawal, extubation trial). [START_REF] Fessler | Inhaled nitric oxide dependency at the end of double-lung transplantation: a boosted propensity score cohort analysis[END_REF]

Conclusion

In conclusion, OR extubation after DLT is an option for COPD/emphysema patients (51.3% of extubated patients were in this group) and cystic fibrosis patients (36.3%) but probably should not be pursued in patients with interstitial lung disease (14.3%). The survival of patients who underwent OR extubation was higher at all time points. Moreover, OR-extubated patients suffered fewer postoperative complications, including PGD3, than ICU-extubated patients. OR extubation could be considered as a clinical marker of a good prognosis; however, the association between OR extubation and improved outcomes should not be interpreted as causality. These results, made possible by the commitment of all the stakeholders of the project, pave the way for adaptation of the ERAS program for LT. A logical subsequent step is to investigate whether OR-extubated patients could benefit from the prompt removal of catheters and tubes (e.g., Swan-Ganz catheter, central venous line, urinary catheter), which are sources of infectious complications, limit early mobilization and early rehabilitation with physiotherapists, and increase costs.

QUESTIONS:

1) Evaluate prognosis of patients extubated in OR after double-lung transplantation (DLT) compared with those extubated in ICU;

2) Identify factors related to successful OR extubation; 3) Evaluate its safety.

CONCLUSION: OR extubation is associated with a favorable prognosis after DLT, but the association should not be interpreted as causality. This fast-track protocol was made possible by the commitment of a team to developing a global strategy to enhance recovery after lung transplantation.

OPERATING ROOM EXTUBATION, A PREDICTIVE FACTOR OF ONE-YEAR SURVIVAL AFTER DOUBLE-LUNG TRANSPLANTATION ONE-YEAR SURVIVAL PREDICTORS

FiguresFigure 1 .

 1 Figures

Figure 2 .Figure 3 .Figure 4 .Figure 5

 2345 Figure 1. Flow chart * Some patients presented several criteria for exclusion from the analysis

Figure 5 Sensitivity

 5 Figure 5

INTRAOPERATIVE MANAGEMENT:FINDINGSFEASIBILITY:

  Combination of short-acting anesthetic drugs, thoracic epidural analgesia, and inhaled nitric oxide (iNO), ECMO for refractory hemodynamic or respiratory failure, and three-step weaning trial (ECMO, iNO, extubation) Of 450 patients, 35.8% were extubated in the OR SAFETY: Four OR-extubated patients were reintubated within 24 hours.

Table 1 .

 1 Donor characteristics and preoperative patient characteristics

	OR extubation	ICU extubation	P
	n = 161	n = 289

Table 1 .

 1 Donor characteristics and preoperative patient characteristics (continued)

	OR extubation	ICU extubation	P
	n = 161	n = 289

Table 2 .

 2 Intraoperative data

	OR extubation	ICU extubation	P
	n = 161	n = 289

Table 2 .

 2 Intraoperative data (continued)

	Values are number (%) and median [interquartile range]
	ICU = intensive care unit; OR = operating room; PGD3 = grade 3 pulmonary graft dysfunction; ECMO
	= extracorporeal membrane oxygenation; iNO: inhaled nitric oxide
	* A major hemodynamic event corresponds to a cardiac arrest, an episode of myocardial ischemia
	sometimes due to a coronary air embolism, an episode of right or left ventricular failure, or a
	hemorrhagic shock.

Table 3 .

 3 Postoperative complications and outcomes

	OR extubation	ICU extubation	P
	n = 161	n = 289

Table 3 .

 3 Postoperative complications and outcomes (continued) ICU = intensive care unit; OR = operating room; PGD = pulmonary graft dysfunction; PGD3 = grade 3 pulmonary graft dysfunction; LOS = length of stay; ECMO = extracorporeal membrane oxygenation

	OR extubation	ICU extubation	P
	n = 161	n = 289

This study was supported by Hospital Foch, 40 rue Worth, The sponsor played no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Conflicts of interest and funding sources

The authors have no conflicts of interest pertinent to the paper to disclose.

Funding was provided by Hôpital Foch, 92150 Suresnes, France. Hôpital Foch played no role in the data collection, analysis or interpretation and will have no right to approve or disapprove publication of the finished manuscript.