Ernest Ahiavi

James A Dawson

Ulas Kudu

Matthieu Courty

M Saiful Islam

Oliver Clemens

Christian Masquelier

Theodosios Famprikis

Mechanochemical synthesis and ion transport properties of Na3OX (X = Cl, Br, I and BH4) antiperovskite solid electrolytes

Keywords: synthesis, ball-milling, antiperovskite, borohydride, ionic conductivity, molecular dynamics Mechanochemical

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

Introduction

Research into solid Li + -and Na + -ion conductors has rapidly escalated over the last decade in view of possible applications in solid-state batteries [START_REF] Famprikis | Fundamentals of inorganic solid-state electrolytes for batteries[END_REF][START_REF] Zhang | New horizons for inorganic solid state ion conductors[END_REF][START_REF] Zhao | Solid-State Sodium Batteries[END_REF]. These efforts have afforded an increasing fundamental understanding of ion migration in the solid state along with the discovery of several previously disregarded families of materials that can sustain fast ion diffusion [START_REF] Ohno | Materials design of ionic conductors for solid state batteries[END_REF][START_REF] Bachman | Inorganic Solid-State Electrolytes for Lithium Batteries: Mechanisms and Properties Governing Ion Conduction[END_REF]. One such family of materials is characterized by the antiperovskite structural arrangement, typically denoted lithiumor sodium-rich antiperovskites, to differentiate from the much studied oxide perovskite lithium-ion conductors of the Li3xLa⅔-xTiO3 archetype [START_REF] Sun | Recent Progress in Lithium Lanthanum Titanate Electrolyte towards All Solid-State Lithium Ion Secondary Battery[END_REF][START_REF] Wu | Utmost limits of various solid electrolytes in all-solid-state lithium batteries: A critical review[END_REF].

With the latest Nobel prize awarded to pioneers of the lithium battery technology, it seems fitting to contribute to this celebratory issue with our work related to one of the laureates, John B.

Goodenough, who has recently been involved in the development of solid-state batteries using antiperovskite electrolytes [START_REF] Braga | Alternative Strategy for a Safe Rechargeable Battery[END_REF][START_REF] Li | Fluorine-Doped Antiperovskite Electrolyte for All-Solid-State Lithium-Ion Batteries[END_REF][START_REF] Braga | Glass-amorphous alkaliion solid electrolytes and their performance in symmetrical cells[END_REF]. Furthermore, significant attention has been generated by highprofile publications on the antiperovskites Li3OCl [START_REF] Zhao | Superionic Conductivity in Lithium-Rich Anti-Perovskites[END_REF] and Na3OBH4 [START_REF] Sun | Rotational Cluster Anion Enabling Superionic Conductivity in Sodium-Rich Antiperovskite Na3OBH4[END_REF] claiming superb ionic conductivities of the order of mS/cm at room temperature for Li + and Na + , respectively.

The interest in the antiperovskite family as solid electrolytes for battery applications arises from several factors, including: i) a simple structural archetype that is prone to iso-and aliovalent substitutions and, as such, to property tailoring [START_REF] Bhalla | The perovskite structure-a review of its role in ceramic science and technology[END_REF]; ii) the absence of (semi)metallic elements, which are at the root of reductive instability with battery anodes [START_REF] Famprikis | Fundamentals of inorganic solid-state electrolytes for batteries[END_REF][START_REF] Schwietert | Clarifying the relationship between redox activity and electrochemical stability in solid electrolytes[END_REF] (in this case Na metal). This leads to expectations of minimal electronic conductivity and electrochemical stability in battery conditions; iii) their soft mechanical properties [START_REF] Deng | Elastic Properties of Alkali Superionic Conductor Electrolytes from First Principles Calculations[END_REF], which are key to facile densification and integration in solid-state batteries. Furthermore, this allows the synthesis of these materials through mechanochemistry, as demonstrated in the present study; and iv) the aforementioned reports of high ionic conductivity [START_REF] Zhao | Superionic Conductivity in Lithium-Rich Anti-Perovskites[END_REF][START_REF] Sun | Rotational Cluster Anion Enabling Superionic Conductivity in Sodium-Rich Antiperovskite Na3OBH4[END_REF] allowing highly efficient and fast charge-discharge cycles of a battery cell.

Stoichiometric Na antiperovskites Na3CX typically include a chalcogenide (C) and a (super)halide (X), with the former and latter occupying the 6-and 12-fold coordinated anion sites, respectively. To our knowledge, the first sodium-rich antiperovskite reported was Na3NO3 (i.e. [Na + ]3[O 2-][NO2 -]) in 1938 by Zintl and Morawietz [START_REF] Zintl | Orthosalze von Sauerstoffsäuren[END_REF][START_REF] Klemenc | Zur Kenntnis der Salpetersäure IX. Über Orthonitrit und Orthonitrat[END_REF][START_REF] Jansen | Neue Untersuchungen an Na3NO3[END_REF]. The archetypical Na3OCl and Na3OBr were then synthesized by Sabrowsky et al. 50 years later [START_REF] Sabrowsky | Na3OCl und Na3OBr, die ersten Alkalimetallchalkogenidhalogenide / Na3OCl and Na3OBr, the First Alkali Metal Chalcogenide Halides[END_REF]. Jansen et al. studied the Na + conductivity of Na3OBr, Na3NO3 and Na3OCN and observed a sharp enhancement of ion transport above a transition temperature specific to each compound, as a signature of an order-disorder phase transition with respect to the orientation of the complex superhalogen anions NO2 -and CN -(paddle-wheel effect) [START_REF] Jansen | Neue Untersuchungen an Na3NO3[END_REF][START_REF] Müller | CN)ONa3, Kristallstruktur und Natriumionenleitfähigkeit[END_REF][START_REF] Jansen | Über die quasi-binären Systeme NaNO2/Na2O und NaCN/Na2O. Phasendiagramme und Natrium-Ionenleitung in Na3O(NO2) und Na3O(CN)[END_REF]. Wang et al. first showed the possibilities for isovalent mixing in the halide site with Na3OCl1-xBrx (0 < x < 1) and Na3OBr1-xIx (0 < x < 0.6), as well as aliovalent substitution of Na + with Ca 2+ , Sr 2+ to increase Na + conductivity [START_REF] Wang | Structural manipulation approaches towards enhanced sodium ionic conductivity in Na-rich antiperovskites[END_REF]. Nguyen et al. highlighted a considerable secondary contribution to the ionic impedance of Na3OBr, attributable to imperfect particle contact, which they alleviated through spark plasma sintering [START_REF] Nguyen | Experimental and Computational Evaluation of a Sodium-Rich Anti-Perovskite for Solid State Electrolytes[END_REF].

Understanding of the atomistic ion conduction mechanisms at play in antiperovskites has mostly been pursued by computational means [START_REF] Dawson | Atomic-Scale Influence of Grain Boundaries on Li-Ion Conduction in Solid Electrolytes for All-Solid-State Batteries[END_REF][START_REF] Dawson | Elucidating lithium-ion and proton dynamics in anti-perovskite solid electrolytes[END_REF]. Whether alkali vacancies or interstitials are the dominant charge carriers in the antiperovskite structure has been a matter of debate [START_REF] Emly | Phase Stability and Transport Mechanisms in Antiperovskite Li3OCl and Li3OBr Superionic Conductors[END_REF]. Studies on the defect energetics on Na3OCl point to NaCl Schottky (pairs of Na + and Cl -vacancies) as the dominant defects [START_REF] Wan | A first principle study of the phase stability, ion transport and substitution strategy for highly ionic conductive sodium antipervoskite as solid electrolyte for sodium ion batteries[END_REF][START_REF] Dawson | Composition Screening of Lithium-and Sodium-Rich Anti-Perovskites for Fast-Conducting Solid Electrolytes[END_REF], whereas, Zhu et al. proposed Na2O Schottky defects (pairs of 2Na + and O 2- vacancies) for Na3OBr on the basis of neutron diffraction [START_REF] Zhu | Sodium Ion Transport Mechanisms in Antiperovskite Electrolytes Na3OBr and Na4OI2: An in Situ Neutron Diffraction Study[END_REF]. In any case, sodium vacancies seem to be the majority Na + defect species in sodium-rich antiperovskites. Theoretical works have also examined the effect of lattice distortions (including symmetry breaking from the cubic aristotype structure) on the phase stability and ion transport [START_REF] Pham | Computational predictions of stable phase for antiperovskite Na3OCl via tilting of Na6O octahedra[END_REF][START_REF] Siegel | Correlating Lattice Distortions, Ion Migration Barriers, and Stability in Solid Electrolytes[END_REF]; still, such distorted alkali anti-perovskites remain elusive experimentally. Considerable computational efforts have also been directed towards the prediction of compositions and design strategies to guide further experimental efforts. A well accepted strategy that has also been confirmed experimentally is the aliovalent substitution of divalent M 2+ on the Na + sites so as to create Na vacancies (M = Mg 2+ , Ca 2+ , Sr 2+ and so on) [START_REF] Wang | Structural manipulation approaches towards enhanced sodium ionic conductivity in Na-rich antiperovskites[END_REF][START_REF] Wan | A first principle study of the phase stability, ion transport and substitution strategy for highly ionic conductive sodium antipervoskite as solid electrolyte for sodium ion batteries[END_REF]. Beyond doping, notable compositions to target experimentally are Na3O0.5S0.5I [START_REF] Yu | Theoretical design of double anti-perovskite Na6SOI2 as a super-fast ion conductor for solid Na + ion batteries[END_REF] Na3SI [START_REF] Siegel | Correlating Lattice Distortions, Ion Migration Barriers, and Stability in Solid Electrolytes[END_REF] and Na3SBCl4 [START_REF] Fang | Sodium Superionic Conductors Based on Clusters[END_REF], which utilize larger chalcogen and halide ions to increase the lattice volume and enlarge the diffusion pathways for sodium.

Another composition of particular interest is also the inverted antiperovskite Na3FS in which the large chalcogen would occupy the 12-fold coordinated anion site and small halogen the 6-fold coordinated anion site [START_REF] Siegel | Correlating Lattice Distortions, Ion Migration Barriers, and Stability in Solid Electrolytes[END_REF]. Beyond studies in the framework of ion conductors, other sodium-rich antiperovskites have also been reported, including Na3(SO4)F [START_REF] Avdontceva | Order-disorder phase transition in the antiperovskite-type structure of synthetic kogarkoite, Na3SO4F[END_REF] and Na2(BH4)(NH2) [START_REF] Somer | α-and β-Na2[BH4][NH2]: Two modifications of a complex hydride in the system NaNH2-NaBH4; syntheses, crystal structures, thermal analyses, mass and vibrational spectra[END_REF], for which no ionic conductivity data have been collected.

In the present study, we report on our efforts aimed at i) demonstrating the efficiency of mechanochemistry as a novel synthetic route for these soft sodium antiperovskite materials; ii) synthesizing for the first time binary-and ternary halide mixtures including BH4 -; iii) providing a holistic discussion of the structure-property relationships in Na-rich antiperovskites, integrating our results in the context of previous findings; and iv) attempting to reproduce and build on the recent promising reports on Na3OBH4.

Methods

Synthesis of sodium oxide (Na2O).

Although anhydrous (super)halides (NaX) are readily available, commercial Na2O reagents often contain significant amounts of impurities, mainly sodium peroxide (Na2O2) and hydroxide (NaOH) (Figure 1a). In previous reports, such commercial powders have been used in the synthesis of Na3OX antiperovskites, in conjunction with excess Na metal [START_REF] Wang | Structural manipulation approaches towards enhanced sodium ionic conductivity in Na-rich antiperovskites[END_REF][START_REF] Nguyen | Experimental and Computational Evaluation of a Sodium-Rich Anti-Perovskite for Solid State Electrolytes[END_REF] and/or under vacuum [START_REF] Nguyen | Experimental and Computational Evaluation of a Sodium-Rich Anti-Perovskite for Solid State Electrolytes[END_REF] to alleviate this issue, assuming the evacuation of H2, O2 or H2O. Here, we have opted to produce 'homemade' Na2O reagent as a first step, by reduction of NaOH by metallic Na (excess), similar to a recent study [START_REF] Zhu | Sodium Ion Transport Mechanisms in Antiperovskite Electrolytes Na3OBr and Na4OI2: An in Situ Neutron Diffraction Study[END_REF], according to:

+ ℃,~ + 1 2 ↑
The reagents were thoroughly mixed using an agate mortar and pestle in an Ar-filled glovebox. The mixture was then loaded into an alumina boat and heated in a vacuum oven (Büchi) connected to a vacuum pump at 300 ˚C for 14 h. The produced hydrogen gas was evacuated and excess sodium metal deposited on a cold trap. This procedure was repeated four times to drive the reaction to completion. We found that without thorough grinding of the reagents between heating steps residual NaOH and Na2O2 were observed in the final product. This synthesis resulted in pure Na2O, free of the aforementioned impurities, as attested by the associated x-ray diffractogram (Figure 1b). Synthesis of Na3OX antiperovskites. The 'homemade' Na2O and commercial Na2S, NaF, NaCl, NaBr, NaI, NaBH4 powders were utilized as reagents. Prior to the synthesis, the halide reagents used were dried under vacuum at 100 °C for 24 h in a glass vacuum oven (Büchi) to remove possible residual moisture. Diffractograms attesting to the purity of the halide reagents are shown in Figure S1.

Equimolar mixtures of pure Na2C (C=O, S) and NaX (X = Br, Cl, I, BH4) were thoroughly ground into fine powders in an Ar-filled glovebox. The precursor powders (typically 1.5 g) were loaded into an 80 mL ZrO2 milling jar containing twelve 10-mm-diameter ZrO2 balls (total mass 36 g). A planetary ball mill (Fritsch Pulverisette 7 Premium) was used for the mechanochemical synthesis at 600 rpm for a total effective milling time of 24 h with a 5 min pause every 20 min of milling. Samples produced in this way are referred to as 'as-milled'.

+ (" # )

To improve crystallinity, the ball-milled antiperovskite powders were hydraulically pelletized (370 MPa) into 13-mm-diameter pellets using a stainless-steel die and annealed in a glass vacuum oven (Büchi) for 13 h at 200 °C under vacuum. Samples produced this way are referred to as 'annealed'.

X-ray powder diffraction. Diffractograms of all antiperovskite samples were measured at room temperature using a Bruker D8 diffractometer with Cu-Kα or Co-Kα radiation (λCu = 1.5418 Å and λCo = 1.7903 Å, respectively). The moisture-sensitive powders were placed in hermetic sample holders under Ar atmosphere in a glove-box. Depending on the sample holder, diffractograms were collected either through a ≈100 μm Be window or through a dome-shaped PEEK cap. The former produces a flat background but attenuates the intensity of Bragg reflections non-uniformly (decreasing absorption with 2θ); the latter produces significant diffuse scattering at low 2θ but does not affect the relative intensity ratio of Bragg reflections allowing for Rietveld refinements. Fitting of the diffractograms was performed with the Le Bail and Rietveld methods as integrated in the FullProf [START_REF] Rodríguez-Carvajal | Recent advances in magnetic structure determination by neutron powder diffraction[END_REF] and Jana 2006 [START_REF] Petrícek | Crystallographic computing system JANA2006: General features[END_REF] software suites.

Impedance spectroscopy. Measurements of electrochemical impedance spectroscopy were made using a frequency response analyser (MTZ-35, Biologic) and an intermediate temperature system (ITS, Biologic). Annealed samples were first pelletized using a 13 mm die in a uniaxial hydraulic press (typically ~750 MPa). The relative density of the pellets measured is reported in Table S1. The pellets were then sandwiched between two graphite paper disks which served as blocking electrodes. The pellets were loaded in an Ar-filled glovebox into a hermetic sample holder (CESH, Biologic) and measured at temperatures ranging from 25 to 100 °C. A frequency range of 30 MHz to 0.1 Hz and an excitation voltage of 0.05 V were utilized. The ionic conductivities were determined by extracting the resistances from the Bode plots (as explained in ref. [START_REF] Famprikis | Composition Dependence of Ionic Conductivity in LiSiPO(N) Thin-Film Electrolytes for Solid-State Batteries[END_REF]) and calculating the conductivities taking the dimensions of the pellets into account. The activation energy (Ea) for Na ion diffusion was calculated from the slope of the Arrhenius plot.

Thermal analysis. Coupled differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) measurements were performed using a NETZSCH STA 449F3 Jupiter housed in an Ar-filled glovebox. Heating and cooling rates of 10 °C/min were utilized, under a constant flow of Ar (50 mL/min). The mass spectra of the evolved gases were recorded using a mass spectrometer.

Vibrational spectroscopy. Infrared spectra were recorded at ambient temperature using a Thermo Scientific (Nicolet iS10) FT-IR system. The borohydride samples were mixed with dry KBr (ca. 90 wt.% KBr and 10 wt.% Na3OBH4 or NaBH4) and pelletized using a 13 mm stainless-steel die and sealed in an air-tight sample holder in an Ar-filled glovebox prior to data acquisition on the antiperovskite. All spectra were recorded in the region 4000-400 cm -1 and the KBr spectrum was subtracted. Raman spectra were acquired using a Raman DXR Microscope (Thermo Fisher Scientific) with an excitation laser beam (λ = 532 nm) at 1 mW laser power using a pinhole slit (25 µm). Na3OBH4 and NaBH4 powders were loaded on glass slides and covered with electrical tape in an Ar-filled glovebox.

Spectra were collected through glass slides in the range 50-3500 cm -1 .

Ab initio molecular dynamics (AIMD) simulations.

The simulations in this work were carried out using density functional theory (DFT) with the Vienna ab initio simulation package (VASP) [START_REF] Kresse | Efficient iterative schemes for ab initio total-energy calculations using a plane-wave basis set[END_REF]. A plane-wave cut-off energy of 400 eV was utilized. The projector augmented wave method [START_REF] Blöchl | Projector augmented-wave method[END_REF] and the PBEsol exchange-correlation functional [START_REF] Perdew | Restoring the Density-Gradient Expansion for Exchange in Solids and Surfaces[END_REF] were employed for all calculations. The k-space was sampled using the gamma-point only with 3×3×3 supercells containing 243 and 135 atoms for Na3OBH4 and Na3OX (X = Cl, Br or I), respectively. To induce Na-ion transport, Na vacancies were added to each supercell at a concentration of 5%. Statistical properties were obtained from simulations of >50 and >100 ps for Na3OBH4 and Na3OX (X = Cl, Br or I), respectively, using the NVT ensemble with the Nose-Hoover thermostat [START_REF] Evans | The Nose-Hoover thermostat[END_REF]. The AIMD calculations for Na3OBH4 were carried out at 600, 700 and 800 K, with a time step of 1 fs to account for the protons. Temperatures above 800 K were tested but resulted in structural instabilities with protons separating from the BH4 tetrahedra. A similar issue was also found by Sun et al. at 1100 K [START_REF] Sun | Rotational Cluster Anion Enabling Superionic Conductivity in Sodium-Rich Antiperovskite Na3OBH4[END_REF]. For Na3OX (X = Cl, Br or I), the simulations were run at 600, 800 and 1000 K, with a time step of 2 fs. Self-diffusion data for Na were obtained from the mean square displacement (MSD) according to

〈&' ( ())〉 = +,-.)
where 〈ri 2 (t)〉 is the MSD, DNa is the diffusion coefficient for Na and t is time. Activation energies for Na-ion diffusion were extracted by fitting to an Arrhenius relationship of the form:

,-. = ,/0 -1. ⁄ 23
where D0 is the Arrhenius pre-factor.

Results and Discussion

Mechanochemical synthesis of Na3CX antiperovskites

A commonly-cited stability criterion for the stability of perovskite structures is the tolerance factor, t, introduced by Goldschmidt [START_REF] Goldschmidt | Die Gesetze der Krystallochemie[END_REF], involving a simple geometrical consideration of the ionic radii of the constituent atoms. For an ABO3 oxide perovskite (and by extension a XCNa3 sodium-rich antiperovskite such as ClONa3), it can be written as:

4 = 6 7 + 6 8 √2(6 + 6 8 ) = 6 : + 6 ; √2(6 < + 6 ; )
where ri is the ionic radius of atom i. t = 1 corresponds to the ideal case of the three spherical ions fitting perfectly in a cube. Deviations from unity indicate size mismatch between the ions and can lead to phase instability and/or distortions from the cubic (anti)perovskite aristotype.

By analogy to classical oxide perovskites, it might be assumed that a range of 0.85 < t < 0.95 might be ideal for such structures, and as such might serve as an adequate predictor of stability for further material development. Figure 2 summarizes the synthesizability of sodium-rich antiperovskites as a function of constitutent anion size, including our attempts in this work through mechanochemistry. and 12-coordinated (Cl -, S 2-, NO3 -, CN -, Br -, BH4 -, I -, IO4 -, BF4 -and PF6 -) anion sizes. Dotted diagonals represent values of the tolerance factor t. Anionic size assigned as the ionic radius or the thermochemical radius tabulated in references [START_REF] Shannon | Revised effective ionic radii and systematic studies of interatomic distances in halides and chalcogenides[END_REF] and [START_REF] Roobottom | Thermochemical Radii of Complex Ions[END_REF][START_REF] Jenkins | Reappraisal of thermochemical radii for complex ions[END_REF], respectively

Multiple oxide antiperovskites Na3OX are synthesizable within a wide range of tolerance factors 0.84 < t < 0.97. The limit of stability for Na3OX seems to be around t = 1, i.e., for superhalides X that are excessively large like IO4 -, BF4 -and PF6 -. Since the size of the two anions greatly influences the lattice volume, Na3OI should then be the the oxide sodium-rich antiperovskite with the highest molar volume. Assuming that higher molar volume could be correlated with ion enhanced transport, it would be desirable to increase it further by replacing O 2-with larger anions on the 6-coordinated site. The natural choice is S 2-and previous computational studies have identified Na3(O0.5S0.5)I [START_REF] Yu | Theoretical design of double anti-perovskite Na6SOI2 as a super-fast ion conductor for solid Na + ion batteries[END_REF] and Na3SI [START_REF] Siegel | Correlating Lattice Distortions, Ion Migration Barriers, and Stability in Solid Electrolytes[END_REF] as promising (oxy)sulfide materials to be synthesized.

As shown in Figure 2, despite multiple attempts, S 2--containing compositions could not be successfully synthesized with the methodology described in this study. Due to the size of S 2-, sulfide Na3SX antiperovskites have much lower tolerance factors with elemental halides (X = Cl, Br, I). For example, the tolerance factor of Na3SI is 0.81. For this reason we also attempted to prepare sulfide compositions with larger superhalides. Still, all attempts on synthesizing pure-sulfide Na3SX proved unsuccessful, in contrast to oxide compositions with similar tolerance factors. For example, Na3SPF6 has a similar tolerance factor to Na3OCN. Further, our exploratory synthesis efforts also covered other sulfide compositions identified by computational studies, such as Li3SI [START_REF] Siegel | Correlating Lattice Distortions, Ion Migration Barriers, and Stability in Solid Electrolytes[END_REF] and Na3FS [START_REF] Siegel | Correlating Lattice Distortions, Ion Migration Barriers, and Stability in Solid Electrolytes[END_REF] and Na3(O0.5S0.5)I, whose synthesis, also proved unsuccessful using our mechanochemical approach.

Diffractograms of the resulting powders of the attempted Na3SX synthesis are shown in Figure S2.

It is obvious from Figure 2 that the tendency for synthesizability seems to be more correlated to the type of element occupying the 6-coordinated site rather than to the tolerance factor (Na3OX are synthesizable over a wide range of tolerance factors from ~0.8 to 1). It is unclear at this point why Lior Na-sulfide antiperovskites remain so elusive and therefore the Goldschmidt tolerance factor based on ionic radii is not a sufficient criterion for the stability of sodium-rich antiperovskites. This fact might also be due to an instrinsic limitation of predicting accurately the Na-C and Na-X bond lengths in such systems: as discussed below, a spherical ion approximation might not be applicable.

We note, nevertheless, that our attempt at an oxysulfide composition with a modest sulfide content Na3O0.7S0.3BH4 yielded a semi-positive result, producing a cubic material indexed in the space group =>3 @ > with a = 4.68 Å (Figure S3). This is significantly larger than the 4.64 Å of the pure oxide Na3OBH4 indicating some incorporation of sulfur in the structure. Such doping of S in oxide sodium-rich antiperovskites should be studied further in the future.

We target our discussion on the Na3OX oxyhalide antiperovskites, which can be perceived as equimolar eutectic solutions of the Na2O and NaX binaries and synthesized from the latter. Here, 'homemade' Na2O (Figure 1) was used for the synthesis of Na3OX in a closed system to ensure purity without the need to evacuate side-products. A distinct advantage of the mechanochemical route is that there is no need for a high temperature treatment; using ball-milling alone the reactions can be driven to completion while, for reference, previous studies report on utilizing temperatures in the range of 300-600 ˚C [START_REF] Sun | Rotational Cluster Anion Enabling Superionic Conductivity in Sodium-Rich Antiperovskite Na3OBH4[END_REF][START_REF] Jansen | Neue Untersuchungen an Na3NO3[END_REF][START_REF] Sabrowsky | Na3OCl und Na3OBr, die ersten Alkalimetallchalkogenidhalogenide / Na3OCl and Na3OBr, the First Alkali Metal Chalcogenide Halides[END_REF][START_REF] Wang | Structural manipulation approaches towards enhanced sodium ionic conductivity in Na-rich antiperovskites[END_REF][START_REF] Nguyen | Experimental and Computational Evaluation of a Sodium-Rich Anti-Perovskite for Solid State Electrolytes[END_REF][START_REF] Zhu | Sodium Ion Transport Mechanisms in Antiperovskite Electrolytes Na3OBr and Na4OI2: An in Situ Neutron Diffraction Study[END_REF][START_REF] Hippler | Structure of Na3OCl[END_REF]. The success of the mechanochemical route is probably linked to the soft nature of these materials (e.g. bulk modulus of ~35 GPa for Na3OCl and Na3OBr [START_REF] Deng | Elastic Properties of Alkali Superionic Conductor Electrolytes from First Principles Calculations[END_REF]).

The high-energy ball-milling of equimolar mixtures of Na2O and NaX results in the straightforward synthesis of Na3OX antiperovskites. This is evident from the diffractograms gathered in Figure 3, which can all be indexed in the =>3 @ > space group. Equimolar mixtures of two or three halides can also be used to produce single-phase antiperovskites. We have prepared in this way for the first time binary-and ternary-mixed-halide antiperovskites Na3OX including BH4 -, namely with X = Cl0.5(BH4)0.5, Br0.5(BH4)0.5, I0.5(BH4)0.5 and Cl0.33Br0.33(BH4)0.33. A single set of diffraction peaks for each diffractogram indicates that the mixed compositions result in homogeneous single-phase materials with disordered occupation of the halide site.

As seen in Figure 3, the Bragg reflections indexed in the =>3 @ > space group shift to lower 2θ angles (higher dhkl) as the halide anion X increases in size, indicating isotropic expansion of the unit cell. The relative peak intensities vary considerably with composition, owing to constructive/destructive interference linked to the ratio of the atomic scattering factors of oxygen and the (super)halogen(s).

This effect is especially obvious for the (100) (110) and (210) peaks which are non-observable in certain compositions due to extinction by destructive interference. Both the relative intensity variation and the evolution of the lattice volume serves as proof of the homogeneous integration of multiple halides in the structure of the binary and ternary compositions. Exemplary Rietveld refinements also validate this conclusion (Figs. S4, S5 and Tables S2,S3).

Structure of Na3OX

In an ideal cubic antiperovskite, oxygen is placed at (0, 0, 0) and sodium at (0, ½ ,0), so that dNa-O=a/2.

Using the tabulated ionic radii [START_REF] Shannon | Revised effective ionic radii and systematic studies of interatomic distances in halides and chalcogenides[END_REF] for Na + and O 2-, each in octahedral coordination (and assuming t=1), the expected sodium-oxygen distance is 2.34 Å and, consequently, the lattice parameter of each oxide antiperovskite Na3OX should ideally be 4.68 Å. From Figure 4, it is evident that the lattice parameter and as such the effective sodium-oxygen distance, is actually lower than the nominal one in all cases except for Na3O(BH4)0.5I0.5 and Na3OI. Similarly, the sodium-(super)halide distance is always significantly larger than expected. This observation should be interpreted in the framework of the unique Na coordination in Na3OX antiperovskites, that is NaO2/6X4/12 (each Na 6-coordinated by two oxygen and four halide ions). This seems to produce, in all cases, shorter Na-O and longer Na-X bonds than would be expected from regular NaO6 and NaX6 octahedra, e.g. in Na2O and NaX crystals.

This 'mismatch' is implicitly captured in the tolerance factor (for all cases t<1) and is alleviated as the X anion becomes larger (i.e. t tends to 1 moving from Cl to I). This mismatch might also suggest a non-negligible degree of covalent interaction between constituents, undermining the spherical-ion approximation central to the idea of ionic radii. (super)halide size assigned as the ionic radius or the thermochemical radius tabulated in references [START_REF] Shannon | Revised effective ionic radii and systematic studies of interatomic distances in halides and chalcogenides[END_REF] and [START_REF] Roobottom | Thermochemical Radii of Complex Ions[END_REF], respectively.

From Figure 4, it is obvious that the cubic lattice parameter is actually a function of the (super)halogen anion size. In other words, the smaller the halogen the more tightly the Na is bound to oxygen and vice-versa, and this should have distinct implications on ion transport. Nevertheless, a linear relationship is apparent between the ionic radius of the (super)halogen and the lattice parameter of the Na3OX antiperovskite, resulting in a Vegard-type behavior. From the data points in Figure 4, we determine this linear relationship to be a=0.50•rX+3.59.

We note that in all cases, the samples synthesized in this work present larger lattice parameters than those observed in literature from high-temperature synthesis (for compositions that have been synthesized before) and in general larger than "expected" by the line of best-fit. This could be interpreted as a tensile macrostrain imparted on the crystal structure by the harsh mechanochemical synthesis route.

Out of the hitherto reported Na3OX antiperovskites, Na3O(NO2) seems to be the single significant outlier to this relationship. This is likely related to the difficulty in assigning unambiguous ionic radii to polyatomic anions in the framework of a spherical anion approximation; in effect depending on the orientation of a polyatomic anion in a given crystal structure its effective size can change. We emphasize that tabulated thermochemical radii [START_REF] Roobottom | Thermochemical Radii of Complex Ions[END_REF] were used for the complex anions in this analysis.

Ion transport in Na3OX

The impedance spectra of the annealed sodium-rich antiperovskites were measured as a function of temperature to derive activation energies using a typical Arrhenius relation. The resulting conductivities are plotted in Figure 5a. In addition, AIMD simulations were performed on several compositions and the Na + -diffusivities were extracted and plotted in Figure 5b. The conductivities measured in this work for Na3OX samples all lie in the range 10 -10 -10 -8 S/cm at room temperature and increase to about 10 -8 -10 -6 S/cm at 100 ˚C. These values are in line with reports in literature except for Na3OBH4, which will be discussed separately below. Ball-milling sodium-rich antiperovskites does not seem to dramatically affect their ionic conductivity, as has been observed for other topical ion conductors, e.g. many members of the Li-P-S family [START_REF] Kudu | A review of structural properties and synthesis methods of solid electrolyte materials in the Li2S -P2S5 binary system[END_REF].

It is clear that the calculated activation energies (0.16-0.29 eV) for Na-ion diffusion are significantly lower than the measured activation energies for ionic conductivity (~0.6-1.0 eV) from impedance measurements. This is a common feature in the literature, with the vast majority of computational studies underestimating Na-and Li-ion activation energies in anti-perovskite solid electrolytes. This has been partially explained in a previous study by the presence of highly-resistive grain boundaries in experimental samples [START_REF] Dawson | Atomic-Scale Influence of Grain Boundaries on Li-Ion Conduction in Solid Electrolytes for All-Solid-State Batteries[END_REF]. Such an interpretation is also consistent with the spread of reported conductivities and activation energies reported for the most studied compositions Na3OCl and Na3OBr. We conclude that the experimentally measured ion transport parameters of sodium rich antiperovskites are quite sensitive to details in the experimental procedures of pellet preparation and measurement of impedance spectra, as shown and discussed recently for a variety of ion conductors [START_REF] Ohno | How Certain Are the Reported Ionic Conductivities of Thiophosphate-Based Solid Electrolytes? An Interlaboratory Study[END_REF].

Although the measured conductivities are quite low in view of practical application, their comparison can yield fundamental understanding to guide further development of this family of materials. Figure 6 compares the ionic conductivity at 100 ˚C and the activation energy of sodium-rich antiperovskites against the size of the halide anion. A qualitative trend is observed: increasing halide size leads to increasing the conductivity and decreasing the activation energy. The conductivity trend can be rationalized based on the greater cell volume concomitant with increasing halide size (Fig. 6). As discussed above, the Na-O distance increases with lattice volume which could lead to weaker coordination, facilitating Na-ion hopping. The activation energy trend can be attributed to the polarizability of the larger ion which renders the lattice softer. Similar trends have been observed on multiple solid electrolyte systems, e.g. the (thio)LISICONs [START_REF] Kanno | Lithium Ionic Conductor Thio-LISICON: The Li2S-GeS2-P2S5 System[END_REF] and the Li6PS5X (X = Cl, Br or I) argyrodites [START_REF] Kraft | Influence of Lattice Polarizability on the Ionic Conductivity in the Lithium Superionic Argyrodites Li6PS5X (X = Cl, Br, I)[END_REF]. These trends are qualitatively reproduced by our AIMD simulations with the activation energy for Na diffusion decreasing monotonically from 0.29 eV for the smaller Cl -to 0.16 eV for the larger I -(Figure 5b).

Structural and transport properties of Na3OBH4

Sun et al. [START_REF] Sun | Rotational Cluster Anion Enabling Superionic Conductivity in Sodium-Rich Antiperovskite Na3OBH4[END_REF] recently reported on Na3OBH4 synthesized by a similar procedure to the one used here and with a very high conductivity of the order of 10 -3 S/cm at room temperature. This conductivity is ~10 7 times higher than what we measured for multiple Na3OBH4 samples we synthesized (Figure 5), including one emulating exactly their synthesis parameters. In order to try and understand this inconsistency, we have performed additional characterization of the Na3OBH4 sample.

The existence of strong covalent B-H bonds in the BH4 -subunit allows for the investigation of this material through vibrational spectroscopy. Raman and FTIR spectra of the Na3OBH4 sample are shown in Figure 7, as compared to those of the NaBH4 reagent. Combining the two techniques the four normal modes of the BH4 -tetrahedron, ν1-ν4, are clearly observable, further attesting its integration in the structure. Peaks below 1000 cm -1 in the Raman spectrum likely correspond to vibrations of the sodium lattice with respect to the anion sublattice, attesting to Na + mobility in the material. A peak at 1452 cm -1 in the FTIR spectrum of Na3OBH4 remains unassigned, but was also observed for a Na2(BH4)(NH2) antiperovskite sample in the literature and is likely a "combination of a fundamental and a lattice mode" [START_REF] Somer | α-and β-Na2[BH4][NH2]: Two modifications of a complex hydride in the system NaNH2-NaBH4; syntheses, crystal structures, thermal analyses, mass and vibrational spectra[END_REF]. The thermograms of Na3OBH4 shown in Figure 8 do not reveal any sign of melting of the sample below 400 ˚C. Indeed, pelletized samples annealed at 300 ˚C maintained their shape and phase purity. This is in stark contrast with a melting temperature of 240 ˚C reported by Sun et al. [START_REF] Sun | Rotational Cluster Anion Enabling Superionic Conductivity in Sodium-Rich Antiperovskite Na3OBH4[END_REF].

Instead our thermograms show a sharp exothermic peak at 425 ˚C followed by a broad endothermic effect centered at 441 ˚C and a distinct rise of the baseline (i.e. heat capacity). The DSC peaks are coupled with a mass loss reaching ~4% by the end of the experiment. From the associated mass spectra (Fig. S6), we identified the majority of the outgassing to be H2 (m/z=2) along with traces of m/z=13, 14, 15 and 16 which are likely attributed to diborane B2H6 (m/z=16) and its molecular fragments. The above leads to an interpretation of the decomposition of Na3OBH4 at 425 ˚C rather than melting. It is noted that the total H content in Na3OBH4 corresponds to approximately 8% of its mass, i.e. ~50% of the hydrogen in the material was released during its thermal decomposition.

Overall, the thermal analysis of our sample shows significantly different behavior than the one reported by Sun et al. [START_REF] Sun | Rotational Cluster Anion Enabling Superionic Conductivity in Sodium-Rich Antiperovskite Na3OBH4[END_REF]. pellets to reach the high conductivity reported and showed that measurements performed on cold-pressed pellets presented resistances in the range of MΩ similar to the results of our experiments. It is plausible that hot pressing could alleviate the effects of blocking grain boundaries [START_REF] Nguyen | Experimental and Computational Evaluation of a Sodium-Rich Anti-Perovskite for Solid State Electrolytes[END_REF][START_REF] Dawson | Atomic-Scale Influence of Grain Boundaries on Li-Ion Conduction in Solid Electrolytes for All-Solid-State Batteries[END_REF]; pellet preparation and measurement protocol has been shown to affect the measured ionic conductivity of various alkali solid-electrolytes, as measured by impedance spectroscopy, within 1-2 orders of magnitude [START_REF] Ohno | How Certain Are the Reported Ionic Conductivities of Thiophosphate-Based Solid Electrolytes? An Interlaboratory Study[END_REF][START_REF] Garcia-Mendez | Correlating Macro and Atomic Structure with Elastic Properties and Ionic Transport of Glassy Li2S-P2S5 (LPS) Solid Electrolyte for Solid-State Li Metal Batteries[END_REF][START_REF] Hayashi | A sodium-ion sulfide solid electrolyte with unprecedented conductivity at room temperature[END_REF]. Specifically for sodium-rich antiperovskites, Nguyen et al. showed that the conductivity Na3OBr could be improved by ~1 order of magnitude at 180 °C via spark-plasma-sintering, as opposed to cold-pressing [START_REF] Nguyen | Experimental and Computational Evaluation of a Sodium-Rich Anti-Perovskite for Solid State Electrolytes[END_REF]. However, it would be surprising for this difference in processing to account for 7 orders of magnitude difference in measured ionic conductivity, as observed here for Na3OBH4. Further studies should focus on the effect of sample preparation on the impedance spectroscopy results, specifically for sodium-rich antiperovskites.

Furthermore, we note that the lower conductivity we measure is closer in line with the conductivities of other sodium-rich antiperovskites reported here and elsewhere and seems to follow the qualitative trends with halide size and polarizability (Figs. 5 and6).

The results from our AIMD simulations also present some significant differences to those of Sun et al.

In the AIMD simulations of Sun et al., zero and two Na hops were reported at high temperatures of 700 and 900 K, respectively, for Na3OBr, while for Na3OBH4, two and five hops occurred at 700 and 900 K, respectively. These results suggest that the rate of Na-ion diffusion at >700 K is greater in Na3OBH4 compared to Na3OBr, which is in contrast to our AIMD results presented in Figure 5b that suggest higher Na-ion diffusion in Na3OBr above room temperature. This discrepancy may result from the fact that the AIMD simulations of Sun et al. were only carried out for 40 ps and with a small 2×2×2 supercell. In contrast, the simulations we report here were performed for over 100 ps and a 3x3x3 unit cell, greatly increasing the statistical significance of our conclusions.

Sun et al. attributed the excellent high conductivity they reported to a rotational motion (orientational freedom) of the BH4 -anion [START_REF] Sun | Rotational Cluster Anion Enabling Superionic Conductivity in Sodium-Rich Antiperovskite Na3OBH4[END_REF]. This is in principle possible; such arguments of couple anionic/cationic mobility (paddle-wheel effect, crystal plasticity) have recently resurfaced in the context of borohydride [START_REF] Sadikin | Modified Anion Packing of Na2B12H12 in Close to Room Temperature Superionic Conductors[END_REF][START_REF] Soloninin | Comparison of anion and cation dynamics in a carbon-substituted closo-hydroborate salt: 1 H and 23 Na NMR studies of solid-solution Na2(CB9H10)(CB11H12)[END_REF][START_REF] Duchêne | Ionic Conduction Mechanism in the Na2(B12H12)0.5 (B10H10)0.5 closo -Borate Solid-State Electrolyte: Interplay of Disorder and Ion-Ion Interactions[END_REF][START_REF] Dimitrievska | Carbon Incorporation and Anion Dynamics as Synergistic Drivers for Ultrafast Diffusion in Superionic LiCB11H12 and NaCB11H12[END_REF][START_REF] Brighi | A mixed anion hydroborate/carba-hydroborate as a room temperature Na-ion solid electrolyte[END_REF][START_REF] Yan | A Lithium Amide-Borohydride Solid-State Electrolyte with Lithium-Ion Conductivities Comparable to Liquid Electrolytes[END_REF] and sulfide [START_REF] Smith | Low-temperature paddlewheel effect in glassy solid electrolytes[END_REF][START_REF] Hanghofer | Fast Rotational Dynamics in Argyrodite-Type Li6PS5X (X: Cl, Br, I) as Seen by 31 P Nuclear Magnetic Relaxation-On Cation-Anion Coupled Transport in Thiophosphates[END_REF][START_REF] Zhang | Coupled Cation-Anion Dynamics Enhances Cation Mobility in Room-Temperature Superionic Solid-State Electrolytes[END_REF][START_REF] Phani Dathar | Li-ion site disorder driven superionic conductivity in solid electrolytes: a first-principles investigation of β-Li3PS4[END_REF][START_REF] Adams | Structural requirements for fast lithium ion migration in Li10GeP2S12[END_REF][START_REF] Famprikis | A New Superionic Plastic Polymorph of the Na + Conductor Na3PS4[END_REF] ion conductors for batteries. Our molecular dynamics simulations indeed show that the BH4 -anion rotates at all the temperatures tested (600-800 K). Nevertheless, the computed Na + diffusivities for Na3OBH4 are still of the same order of magnitude as those observed for other sodium-rich antiperovskites examined (Figure 5b), and are also in qualitative agreement with our impedance results (Figure 5a). Based on our analysis, we conclude that BH4 -rotations are likely and could lead to a decreased activation energy for conduction. However, we cannot replicate the overall ionic conductivity or diffusivity of Na + previously reported, neither by experimental impedance measurements nor by AIMD simulations.

Conclusion

We have reported here the efficacy and efficiency of mechanochemistry (ball-milling) for the synthesis of a wide variety of sodium-rich antiperovskite materials, Na3OX (X = Cl, Br, I, BH4). Through utilization of pure Na2O, these materials can be obtained in a single-step, without the need for annealing. Using our diffraction data, impedance spectroscopy and molecular dynamics simulations, we investigate the effect of halide substitution on the interrelated structural and ion transport properties of Na3OX (X = Cl, Br, BH4). We show that the (super)halogen size controls the lattice volume and implicitly the Na-ion conductivity of these materials. In parallel, the polarizability of the (super)halogen controls the activation energy for conduction through its effect on the lattice softness. We also examine the recent reports of high ionic conductivity in Na3OBH4 which we were unable to reproduce. Both our impedance spectroscopy experiments and molecular dynamics simulations indicate that Na3OBH4 is not a positive outlier in terms of its ion transport, and exhibits a similar Na-ion conductivity to other sodium-rich antiperovskites.

The ionic conductivities of the undoped materials measured in this fundamental study are of course still too low to envisage any practical application. Future perspectives to increase the ionic conductivity would include the utilization of larger, more polarizable anions on the six-coordinated site, e.g. replacing the O 2-by S 2-. Although full sulfide compositions could not be synthesized, we show here that partial replacement of O 2-by S 2-is possible and leads to the expected increase in lattice volume. Future studies should investigate whether such substitution significantly affects ion transport. In addition, introducing vacancies by aliovalent substitutions of divalent cations (e.g. Mg 2+

or Ca 2+ [START_REF] Wang | Structural manipulation approaches towards enhanced sodium ionic conductivity in Na-rich antiperovskites[END_REF][START_REF] Wan | A first principle study of the phase stability, ion transport and substitution strategy for highly ionic conductive sodium antipervoskite as solid electrolyte for sodium ion batteries[END_REF]) on the sodium site has been proven to be an effective strategy to increase ionic conductivity. These strategies could be combined with the halide mixing demonstrated in this work to increase the ionic conductivity in sodium-rich antiperovskites.

Figure 1 :

 1 Figure 1: [single column] X-ray diffractograms of a) commercial and b) 'homemade' Na2O, including profile fits. Samples were placed within a moisture-and air-free cell capped with a Be window. Measured Na2O2 and NaOH impurities present in the former are absent in the latter.

Figure 2 [ 1 .

 21 Figure 2 [1.5 column]: Summary of Na3CX synthesizability as a function of 6-coordinated (F -, O 2-, S 2-and Se 2-)

Figure 3 [

 3 Figure 3 [single column]. X-ray diffractograms of annealed antiperovskites in order of increasing lattice parameter. Bragg peak positions correspond to the =>3 @ > space group. Na3OCl0.33Br0.33(BH4)0.33 and Na3OBr0.5(BH4)0.5 samples were measured in PEEK-dome cells and the associated diffuse scattering was subtracted as background. The remaining samples were measured through an airtight sample holder featuring a Be window. BeO peaks in the Na3OBr samples originate from slight oxidation of the Be and denoted with ▼.

Figure 4 [ 1 .

 41 Figure 4 [1.5 column]: Relation between (super)halogen anion size, rx, and cell parameter, a, of cubic Na3OX sodium-rich antiperovskites. Data sorted depending on their provenance (literature or this work) and based on whether they correspond to a mixed-halide composition. Literature data included from Wang et al. (Na3OCl1-xBr and Na3OBr1-xI) [22], Hippler et al. [47] (Na3OCl), Jansen et al. (Na3ONO2 [18] and Na3OCN [20]), Sabrowsky et al. [19] (Na3OCl and Na3OBr), Zhu et al. [29] (Na3OBr), Nguyen et al. [23] (Na3OBr) and Sun et al. [12] (Na3OBH4). All data points represented in the figure are tabulated in SI Tables S4, S5. Dotted lines represent different values of the tolerance factor calculated using rNa VI =1.02 Å and rO VI =1.40 Å [44].The yellow line represents a linear fit across all data points. (super)halide size assigned as the ionic radius or the

Figure 5 [

 5 Figure 5 [single column]: Arrhenius plots of (a) conductivity and (b) diffusivity for several Na3OX antiperovskites. Conductivities in (a) measured by impedance spectroscopy. Na + diffusivities in (b) extracted from AIMD simulations. The activation energies Ea were derived by the slope of the linear fit of ln(σT) or ln(D) versus 1/T.

Figure 6 [

 6 Figure 6 [Single Column]: Plot of the log (σ) and activation energy versus A-site anion radii for several sodium-rich antiperovskites.

Figure 7 [

 7 Figure 7 [single column]: Vibrational (Raman and FTIR) spectra of annealed Na3OBH4 and NaBH4 with assignments.

Figure 8 [

 8 Figure 8 [single column]: Differential scanning calorimetry and thermogravimetric analysis

Acknowledgements

E.A. acknowledges the RS2E (https://www.energie-rs2e.com/en) and CNRS for their financial support in the form of a 6-month internship scholarship in Amiens. T.F. acknowledges the Alistore ERI (http://www.alistore.eu/) and CNRS for their financial support in the form of a joint PhD scholarship between Amiens (France) and Bath (UK). J.A.D. and M.S.I. gratefully acknowledge the MCC/Archer consortium (EP/L000202/1) for computational resources. J.A.D. also gratefully acknowledges Newcastle University for funding through a Newcastle Academic Track (NUAcT) Fellowship.


Dr Carole Philipponnet
email: cphilipponnet@chu-clermontferrand.fr

MD Julien Aniort

MD Bruno Pereira

MD PhD Kazra Azarnouch

MD Mohammed Hadj-Abdelkader

MD PhD Pascal Chabrot

MD Anne-Elisabeth Heng

MD Bertrand Souweine

Systematic Review of Atrial Vascular Access for Dialysis Catheter

Keywords: Dialysis catheter, hemodialysis, intra-atrial catheter, exhausted vascular accesses

Introduction

Over the past decade there has been a steady increase in the prevalence of end stage renal disease (ESRD) worldwide, with more than 2 million patients requiring renal replacement therapy (RRT). Hemodialysis is the major modality of RRT in 70 to 90% of patients, who need well-functioning vascular access for the procedure.

We report two hemodialysis patients with exhausted venous access who underwent atrial vascular access for tunneled dialysis catheter (TDC) placement to provide RRT, in one case for ESRD and for prolonged acute kidney injury (AKI) in the other. We combined these two patient reports with all previously published cases involving a similar intravascular device to carry out a systematic meta-analysis.

Methods

Study selection

The data of the two patients in our center with an intra-atrial hemodialysis catheter inserted between January 2010 and October 2019 were recorded. To identify relevant articles and abstracts of previously published cases of patients who had undergone the same procedure, a systematic literature search was performed using medical subject headings (MESH) in EMBASE, CENTRAL and MEDLINE (1980 to April 2019). The search was restricted to English language publications involving humans. The keywords used were ("renal dialysis"[MH] OR "hemodialysis"[TW] OR "kidney dialysis"[TW] OR "haemodialysis"[TW] OR "extracorporeal dialysis"[TW] OR "extracorporeal dialyses"[TW] OR "renal dialysis"[TW] OR "renal dialyses"[TW] OR "dialysis renal"[TW] OR "hemodialyses"[TW]) AND ("cardiac AND catheter*[TW])).We also hand-searched abstracts from international meetings.

Inclusion/exclusion criteria

The inclusion criteria for studies (including case reports) and patients were ESRD requiring hemodialysis and use of an intra-atrial hemodialysis catheter. The search process, eligibility assessment and data extraction were performed independently by two physicians (CP and BS). The study was performed in accordance with the PRISMA statement : Flow chart is in Figure 1; Prisma checklist in Supplementary file S1. Prospero register number :

CRD42019115344.

Quality assessment

Quality assessment was made independently by three investigators (CP, BS and BP) using the framework developed by Murad et al. to evaluate the methodological quality of case reports/series [START_REF] Murad | Methodological quality and synthesis of case series and case reports[END_REF]. The level of evidence on this pyramid ranges from 0 to 10, with five items being measured and awarded 0, 1 or 2 points each. We assessed case and case series quality with a dedicated tool based on the criteria of Pierson, Bradford Hills and the Newcastle-Ottawa scale [START_REF] Murad | Methodological quality and synthesis of case series and case reports[END_REF]. Of the 8 items, 5 were analyzed in all the case and case series but the 4th, 5th and 6th items were considered as not relevant (applicable to cases of adverse drug events). The items were rated on a scale of 10 points: 0, not satisfactory; 1, partially satisfactory; and 2, satisfactory. The first item was considered satisfactory if the study described explicitly all the patients who had an IATDC over a certain period of time.

The second item was considered satisfactory if exposure was adequately ascertained. The third was considered satisfactory if outcome was adequately ascertained with catheter patency and patient's outcome. The seventh item, which assesses whether follow-up was long enough for outcomes to occur, was considered satisfactory either when a competitive event occurred (kidney transplantation, switch from hemodialysis to peritoneal dialysis or hemodialysis weaning) or when follow-up duration was at least 25 months, which corresponds to the median survival time of our study population. The seventh item was considered partially satisfactory when follow-up duration was between 7 and 24 months, with 7 months corresponding to the first interquartile of the median survival time of our study population. The last item was considered satisfactory if a surgeon could replicate the insertion procedure using the surgical description. Study quality is detailed in Supplementary File S2.

Data management and statistical analysis

Statistical analysis was performed with Stata software (version 13; StataCorp, College Station, TX, USA). For descriptive analyses, data were presented as individual data for case reports and as median [interquartile range] for case series. All analyses took into account between-and within-study variability. To address the non-independence of data due to clustering by study, random-effects models were preferred over the usual statistical tests.

The percentage of alive patients was estimated with the random-effects model as described by Der Simonian and Laird (2). The statistical heterogeneity in results was assessed on confidence intervals and and I², which quantifies inconsistency across studies describing the percentage of the variability in effect estimates that is due to heterogeneity rather than sampling error. Values of I² range between 0 and 100% and are typically considered low at < 25%, moderate at 25-50%, and high at > 50%. Overall survival was then estimated, excluding study for which individual follow-up data were not available [START_REF] Oguz | Right intra-atrial catheter placement for hemodialysis in patients with multiple venous failure[END_REF], by the Fine and Gray method (3), with censoring at the date of death and at the date of kidney transplantation, switch to peritoneal dialysis and renal recovery, defined as competing events. This analysis concerned 24/51 patients.

Results

Patients

The first patient was a 58-year-old man with mesangial IgA nephropathy requiring hemodialysis and placement of a left radiocephalic AVF. His medical history included ischemic cardiopathy and severe arteritis treated by aortobifemoral bypass. He underwent unsuccessful kidney transplantation, which resulted in hyperimmunization. Peritoneal dialysis was ruled out because of anuria and poor compliance.

A tunneled dialysis catheter (TDC) was placed in the right internal jugular vein after AVF thrombosis had occurred. It was removed when a left humeral-cephalic AVF was functional.

The AVF required multiple angioplasties for stenosis and was ultimately occluded by

Literature review

The above procedure of intra-atrial hemodialysis catheter insertion has been described in four case reports (4-7) and four small case series [START_REF] Yaşa | Placing of Permanent Catheter through Right Anterior Mini Thoracotomy in Patients with Chronic Renal Failure[END_REF][START_REF] Agrawal | Intracardiac access for hemodialysis: a case series[END_REF][START_REF] Oguz | Right intra-atrial catheter placement for hemodialysis in patients with multiple venous failure[END_REF][START_REF] Pereira | Life-saving vascular access in vascular capital exhaustion: single center experience in intra-atrial catheters for hemodialysis[END_REF]. The quality assessment of the studies is given in Supplemental file S2. With the addition of our 2 patients, a total of 51 patients were included in the meta-analysis. Their characteristics and outcomes are shown in Table 1. All the patients had exhausted conventional vascular accesses: they were not suitable for peritoneal dialysis or emergency kidney transplantation. All the IATDCs were inserted by a cardiovascular surgeon using the same procedure as that described in our first case report. Six patients developed IATDC-related sepsis one of whom died as a result. At the end of follow-up 38/51 patients were still alive (Figure 2). Seven patients died within 15 days following IATDC insertion: three catheter-related deaths and four unrelated catheter deaths (myocardial infarction N=2, sepsis N=1, metabolic N=1). Six additional patients died later than 15 days after IATDC insertion, from non-catheter-related sepsis (N=2), cerebrovascular events (N=2), neoplasia (N=1), and unknown causes (N=1). The 24/51 patients for whom individual follow-up data were available had a median survival time of 25 [7-not applicable] months (Figure 3) whereas the median survival described in Oguz et al., study with no individual follow-up data available, was 27.5±14.

.

Discussion

Therapy for end stage renal disease (ESRD) requires kidney transplant or RRT including peritoneal dialysis and hemodialysis. Hemodialysis is sometimes the only technique that can be performed in patients with both contra-indication to kidney transplant (e.g. patients with active tumor growth or very severe polyvascular disease) and peritoneal dialysis (e.g.

patients with prior abdominal surgeries). In these patients, the lack of vascular access results in fatal outcome. The recommended access for hemodialysis in ESRD patients is an arteriovenous fistula (AVF) or a vascular graft. However, recourse to central venous catheters remains essential for patients whose chronic renal disease is diagnosed only at the end stage or in whom an arteriovenous fistula cannot be created or maintained. When it is necessary to use permanent dialysis catheters it is recommended to use tunnelled dialysis catheters (TDC) inserted in the internal jugular vein.

Exhaustion of conventional vascular accesses is one of the greatest challenges that nephrologist and patients have to face. TDC exposure can result in venous stenosis and occlusions and superior vena cava syndrome and/or vascular access loss [START_REF] Agarwal | Complications of vascular access: Superior vena cava syndrome[END_REF]. Most recent works on innovations in chronic hemodialysis catheters have focused on new materials (such as carbothane and polyurethane) and new designs to prevent catheter-associated complications [START_REF] Agarwal | Innovations in vascular access for hemodialysis[END_REF].

Several unconventional salvage-therapy routes for TDC placement have been used in patients with no upper body venous access [START_REF] Rahman | Dialysis catheter placement in patients with exhausted access[END_REF] including: (i) needle recanalization (through a thrombosed vessel or by creating a new tract to the central vasculature through a small venous collateral or through the subcutaneous tissues [START_REF] Athreya | Sharp recanalization of central venous occlusions: a useful technique for haemodialysis line insertion[END_REF][START_REF] Funaki | Radiologic placement of tunneled hemodialysis catheters in occluded neck, chest, or small thyrocervical collateral veins in central venous occlusion[END_REF]), (ii) a translumbar approach (direct percutaneous puncture in the infrarenal inferior vena cava) [START_REF] Rajan | Translumbar placement of inferior vena caval catheters: a solution for challenging hemodialysis access[END_REF][START_REF] Power | Translumbar central venous catheters for long-term haemodialysis[END_REF], (iii) a transhepatic approach (direct percutaneous puncture in the inferior vena cava via the right or middle hepatic vein) [START_REF] Po | Transhepatic PermCath for hemodialysis[END_REF][START_REF] Stavropoulos | Percutaneous transhepatic venous access for hemodialysis[END_REF],and (iv) a transrenal approach (direct percutaneous puncture in the inferior vena cava via the renal vein) [START_REF] Dewan | Venous access via the renal vein: a technical innovation[END_REF][START_REF] Law | Hemodialysis catheter insertion using transrenal approach[END_REF]. Intra-atrial placement is an alternative strategy.

To the best of our knowledge, the present study collates all published cases of patients with an IATDC. As shown, IATDC exchange or removal for dysfunction, thrombosis or infection was scarce suggesting that IATDC patency was good, achieved adequate blood flow rates, and that IATDC placement was associated with prolonged survival.

In the US Renal Data System, 510 000 ESRD patients initiated hemodialysis between 2006 and 2010. Of the 82,5% patients receiving dialysis with a TDC, 78% had 1-year survival and 45% 5 year-survival with a median survival time of 3 years [START_REF] Malas | Trends in incident hemodialysis access and mortality[END_REF]. In our meta-analysis, median survival time in patients with an IATDC was 25 [7-NA] months (Figure 3). These findings suggest that the survival time observed in patients with an IATDC is lower than in patients with conventional TDC. However, the population with an IATDC formed a subgroup of patients with highly severe comorbid conditions.

Our study has several strengths. First, we performed a quality assessment of cases and case series with a validated tool [START_REF] Murad | Methodological quality and synthesis of case series and case reports[END_REF]. Second, we identified for the first time all patients with an IATDC and describe the successful use of an unrecognized technique as salvage therapy.

Our study has also several major limitations. First, the patients were retrospectively identified in our center and in documented reports and hence we cannot rule out the possibility that some with IATDC were not included. However, a randomized controlled trial would have been impossible because there was no other alternative therapy. Second, only 51 patients were included in the analysis. At the same time, however, IATDC is a very rare procedure.

Third, individual data from one case series were not available and hence these patients could not be included in the Kaplan Meier analysis [START_REF] Oguz | Right intra-atrial catheter placement for hemodialysis in patients with multiple venous failure[END_REF].

In conclusion, IATDC is an unconventional but safe procedure for adequate vascular access in hemodialysis patients with exhausted venous access. The technique requires a collaborative multidisciplinary approach involving radiologist, cardiac surgeon and nephrologist.

Atrial vascular access for TDC placement can potentially be lifesaving.

Disclosures:

-Author financial disclosures :none -Funding statement:

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors".

-Competing Interests Statement:

This research has any competing interests

FIGURES LEGENDS:

  thrombosis. A second TDC was placed in the left internal jugular vein. The clinical course was complicated by five TDC-related septic shocks which required admission to the intensive care unit, systemic antibiotics and a TDC replacement in the interventional radiology department after venous dilatation. All CT-scan and angiographies carried out to assess the vascular network showed extensive thrombosis of the brachiocephalic vein confluence and the proximal portion of the superior vena cava. The patient underwent aortic valve replacement for severe aortic stenosis and coronary artery bypass graft. During the cardiac surgery the TDC was ablated and replaced by a new TDC directly inserted into the superior vena cava. Because of malfunction, the TDC was exchanged over a guidewire by the interventional radiologist. A new TDC-related septic shock occurred, the TDC was removed in the operating room, and systemic antibiotics were introduced for long-term treatment. A temporary hemodialysis catheter was placed at the right femoral site for 15 days, and replaced by a TDC inserted directly into the right atrium by the cardiac surgeon as salvage therapy (Figure2). Trans lumbar, trans hepatic or trans renal TDC are also salving approach for the vascular access. In our center, we had no experience on these techniques and a multidisciplinary meeting retained the indication of an IATDC.The surgical procedure was as follows. Approach by right anterior thoracotomy at the 3 rd intercostal space; partial adhesiolysis to free up the right lateral pericardium surface; opening of this segment of the pericardium and placement of two cuffs up against the Teflon tips on the right atrium, ready to hold the hemodialysis catheters in place; placement of Surgicel ® fibrillar™ hemostat in the lumens to facilitate remote hemostasis if catheter ablation is needed; catheter tunneling via the intercostal space, just below the thoracotomy space; second tunneling path toward the lateral face of the right pectoralis major and catheter exchange over guidewire; layer-by-layer closure of the various incisions; end-of-procedure transesophageal echocardiogram to check the position of the two catheter tips. Any adverse events associated with intra atrial TDC catheter placement such as arrhythmia, troponin elevation, myocardial dysfunction were noted. Nineteen months later, the patient died of metastatic bronchoalveolar carcinoma with a functional IATDC.The second patient was a 30-year-old man with no past medical history admitted to the intensive care unit after a car accident that had caused multiple bone fractures, dissection of the left renal artery, and ischemic necrosis of the colon requiring multiple orthopedic surgeries and colectomy with ileostomy. Surgical and radiological attempts to restore left kidney perfusion failed. During his ICU stay the patient developed multiple episodes of septic shock that required courses of antibiotics including nephrotoxic antibiotics. He received several injections of iodinated contrast agents for diagnostic imaging and interventional radiology treatments.RRT for AKI was initiated using a left internal jugular temporary hemodialysis catheter subsequently changed at the right and left femoral sites. All the catheters were complicated by septic thrombophlebitis and finally removed. A CT-scan was performed to identify an insertion site appropriate for venous access. It showed multiple thrombosis of the left internal jugular extended to the left innominate venous trunk, at the superior vena cava, the right brachiocephalic artery and at the initial segment of the right internal jugular vein, and of the right and left iliac veins. Peritoneal dialysis was ruled out because of prior abdominal surgery. Thus, the cardiovascular surgeon placed a new TDC directly into the right atrium to allow RRT using the surgical procedure described above. Four months later the patient recovered kidney function, and the IATDC was removed at bedside without additional precautions compared to the removal of tunneled catheters. On the other hand, systematic monitoring was carried after removal by ultrasound to ensure the absence of pericardial effusion. No TDC complication occurred with this last TDC. Two years later, the patient was still alive and free from dialysis.

Figure 1 :Figure 2 :Figure 3 :

 123 Figure 1: Prima Flow Diagram

Acknowledgements

We thank Jeffrey Watts for his help with traduction.

Supplementary material :

S1 : Prisma checklist S2 : Quality assessment of the studies Supplementary information is available at KI Report's website.