Haemodynamic Effect of Dexmedetomidine During Pediatric Kidney Transplantation: A Single-Center Retrospective Study

Haemodynamic Effect of Dexmedetomidine During Pediatric Kidney Transplantation: A Single-Center Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Haemodynamic Effect of Dexmedetomidine During Pediatric Kidney Transplantation: A Single-Center Retrospective Study Matéo Monteil, Alexis Chenouard, Gwenaëlle Roussey, Rémi Bernardon, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4009118/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Sep, 2024 Read the published version in Pediatric Nephrology → Version 1 posted 4 You are reading this latest preprint version Abstract Background Dexmedetomidine is increasingly used for its hemodynamic stability property during general anesthesia. However, there is no data on pediatric kidney transplant recipients (pKTR). Our study investigates the hemodynamic effect of perioperatively administered dexmedetomidine in pKTR. Methods Between 2019 and 2023, all pKTR below 18 years were studied retrospectively at Nantes University Hospital. Intraoperative hemodynamic status was compared between patients who had received dexmedetomidine during kidney transplantation (DEX group) and patients who had not (no-DEX group). Mean arterial pressure (MAP) and heart rate (HR) were monitored throughout the duration of anesthesia and compared. Graft function was assessed by creatinine levels and Glomerular Filtration Rate (GFR) at specific time points. The use of fluid and vasoactive drugs peri-operatively and within 24 hours after surgery was also studied. Results 38 patients were included, 10 in the DEX group et 28 in the no-DEX group. Intraoperative HR was similar between the two groups; however, MAP was significantly higher (mean difference 8, standard deviation [SD: 2–14] mmHg, p = 0,034 ) in the DEX group. No differences were found regarding the use of fluid and vasoactive drug therapy between groups. Glomerular filtration rate at one month was significantly higher in DEX group ( p = 0,009 ). Conclusion Children receiving intraoperative dexmedetomidine during a KT presented higher perioperative MAP compare to children receiving other sedative agents. DEX group also showed better graft function at one month. The direct impact of dexmedetomidine on immediate post-operative graft function in pTKR should be studied in a prospective multicenter randomized study. dexmedetomidine kidney transplant hemodynamic pediatric mean arterial pressure graft function Figures Figure 1 Figure 2 Figure 3 Introduction Dexmedetomidine is a highly selective alpha-2 agonist mostly used in anesthesia for its sedative properties and its weak respiratory depressant effect. Among its many pharmacological properties we can pick up : hemodynamic stabilization action [ 1 ], improved local tissue perfusion [ 2 , 3 ] and reduced ischemia-reperfusion damage to transplanted organs [ 4 , 5 ]. It also occupies an increasing place in Opioïd-Free Anesthesia (OFA) strategy as part of Enhanced Recovery After Surgery (ERAS) protocols [ 6 ]. Many studies and clinical trials have focused on its use in thoracic surgery and heart transplantation and find encouraging data on the positive impact of this molecule on post-operative renal function [ 7 , 8 ]. In the field of adult kidney transplant (KT), use of perioperative dexmedetomidine could be associated with a beneficial effect in terms of recovery of graft function [ 9 – 11 ], but no data are available to date in pediatrics. A multicenter study realized in 2017 noted the disparity of anesthesic practices in French pKTR and point the lack of recommendation concerning the use of dexmedetomidine in this context [ 12 ]. Yet, since 2019 at the pediatric University Hospital of Nantes, the dexmedetomidine is increasingly used in perioperative anesthesic protocol of KT. Thus, in this pilot study, we aimed to assess retrospectively the intraoperative hemodynamic effect of an anesthesic protocol with dexmedetomidine (DEX group) compared with a protocol without dexmedetomidine (no-DEX group) in pKTR. MATERIALS ET METHODS II.1. Study population and design This single-center, retrospective, observational study was conducted at Nantes University Hospital, a tertiary children’s hospital. It was approved by the local Research Ethics Board of the University of Nantes, France on April 2023 (N°23-54-04-190). The requirement for parental informed consent was waived. All children, aged less than 18 years old, hospitalized for a KT in Nantes pediatric hospital between January 2019 and June 2023 were eligible. Patients without intra-operative hemodynamic data recording were excluded (Figure 1) . Fig1 Flow-chart Fig1 was made using Microsoft Powerpoint We compared patients who received dexmedetomidine intraoperatively (DEX group) and those who did not (no-DEX group). II.2. Anesthesic protocol All pKTR received anesthesia and monitoring according to local protocols. Choice of sedative agents used was left to discretion of the anesthesiologist in charge of the patient. In the group without dexmedetomidine (no-DEX), induction was performed by intravenous way with propofol or thiopenthal combined with morphinic (sufentanil or remifentanil), or by a combination of inhalatory and intravenous way with sevoflurane and sufentanil. Maintenance anesthesia was provided by morphinic (sufentanil or remifentanil) and sevoflurane, which could be associated with propofol. In the dexmedetomidine group (DEX), induction was assumed by dexmedetomidine and/or propofol with or without sufentanil or by sevoflurane and dexmedetomidine. Maintenance included dexmedetomidine and sevoflurane, sometimes combined with sufentanil or propofol. In both groups, patients were curarized by atracurium throughout the anesthesia. Because the dexmedetomidine administration protocol was not clearly defined, each child received a variable dose of medication by continuous intravenous route ranging from 0,7 to 1,4 µg/kg/h after a loading dose. Patient impregnation with the drug was assessed empirically by the anesthesiologist after a drop in heart rate on the continuous monitoring occurs. Dexmedetomidine infusion was stopped on arrival in Intensive Care Unit (ICU). II.3. Collected data We collected hemodynamic data for each patient during all transplant surgery thanks to anesthesia software available at our hospital: Pégase and Anesthesia Consultation . Vital constants of interest (MAP and HR) were recorded every 5 minutes throughout the duration of anesthesia ( i.e. from anesthesic induction to the arrival in post-operative recovery room). We have also recorded the intraoperative hemodynamic status by use and total doses, relative to weight, of vasoactive drugs (norepinephrine, dobutamine and ephedrine) and vascular filling solutions (ringer lactate, serum saline, albumin 4%) required during anesthesia; and the immediate postoperative hemodynamic status (less than 24 hours), through need of hemodynamic support like vasopressor drugs (norepinephrine), vascular filling solutions or use of diuretics (furosemide) The graft function recovery was assessed by decreasing of serum creatinine (via a serum creatinine decline ratio at hour 0 (H0), corresponding to last pre-transplantation serum creatinine, versus H1, H24, H48, H168; the glomerular filtration rate (GFR) at H24, H48, H168 and at the end of first month); and the onset of delayed graft function (DGF), defined as the need of dialysis during first week post-transplant. GFR was calculated with Schwartz formula 2009 : GFR = 36.5 x (height [cm] / serum creatinine [µmol/L]) [13]. We collected the mean vascular resistance index of the graft, assessed on the first renal ultrasound-doppler. The postoperative analgesia quality was assessed by the maximum dose of morphine used (continuous flow rate expressed in mg/kg/day). Epidemiological and clinical data and biological results were extracted from paper and computerized patient files ( Powerchart software). Other data were extracted from organ donor records available on the agence de la biomédecine ( ABM ) national registry. II.4. Statistical analysis Continuous data were presented as median value with interquartile ranges (25 th and 75 th percentiles) and categorical data as number and percentage. Comparisons of continuous and categorical data between the 2 groups (DEX and no-DEX) were performed by using the non-parametric Mann Whitney and Chi2 tests, respectively. To account the repeated measurements of MAP and HR variables, a linear mixed model on longitudinal data adjusted for the random effect of each patient was used for the comparison between groups. This model was also adjusted for age, group and anesthesia duration. A p-value less than 0.05 was considered significant. Statistical analysis was performed using R software (version 4.2.1) and GraphPad Prism (version 8.0.2). Results III.1. Participants Between January 2015 and June 2023, 38 patients were included for this study. 28 received an anesthetic protocol without dexmedetomidine (no-DEX group) and 10 with dexmedetomidine (DEX group) ( Figure 1 ). Baseline characteristics and data likely to influence graft prognosis in both groups are presented in Table 1. Median age of DEX group patients was 6.9 years versus 14.1 years in no-DEX group ( p = 0.144 ). Median duration of cold ischemia was respectively of 327 minutes and 610 minutes in DEX and no-DEX groups ( p = 0.240 ). There was 50% of living-donor transplant in DEX group versus 18% in no-DEX group ( p = 0.048) . We found no significant differences between the two groups for the other selected criteria. III.2. Hemodynamic effect Evolution of MAP and HR during anesthesia is shown in Figure 2 . Intraoperative MAP was significantly higher in DEX group compared to no-DEX group, independently of patient age and anesthesia duration (mean difference + 8 [IQR: 2-14] mmHg, p = 0.034 ). No difference was observed concerning the HR in the 2 groups ( p = 0.787 ). Fig 2 Evolution of MAP (A) and HR (B) during anesthesia in DEX and no-DEX groups 0 min = Anesthetic induction Last PAM and HR measurements = last measurements taken during anesthesia Mean values with standard deviation (SD) are shown Fig2 was made using GraphPad Prism software In addition, we observed no significant difference between the 2 groups in the quantity of vascular filling fluids delivered, nor in the use of vasoactive drugs (norepinephrine, ephedrine, dobutamine) ( Table 2 ). Postoperative needs in terms of vascular filling, vasoactive amines or diuretics were equivalent in both groups ( Table 3 ). III.3. Graft function recovery We observed a statistically significant greater serum creatinine decline ratio from H1 to H168 in the DEX group compared with the no-DEX group (H1: p = 0.008 ; H168: p < 0.001) . For example, at H1, median creatinine decreased by 17% in the DEX group versus 5% in the no-DEX group. GFR at H24, H48, H168 and one month post-transplant were also significantly higher in the DEX group ( p < 0.001 at H168). These results are illustrated in Table 3 and Figure 3 . Fig 3 Evolution of blood creatinine from H1 to H168 versus baseline (last blood creatinine before transplantation) Green points figured living-donor transplants in both groups Red points figured deceased-donor transplants Fig3 was made using GraphPad Prism software There was no statistical difference between groups regarding DGF ( p = 0.281 ). Data for living and deceased donors pKTR are available in supplementary 1 and supplementary 2 . Discussion In this pilot retrospective study, the use of dexmedetomidine as a continuous infusion for anesthesia in children with KT was associated with a perioperative higher MAP, compared with anesthesia without this molecule. This observation does not seem to be related to a different management of hemodynamic support between the 2 groups. Indeed, we observed no differences regarding quantities of vascular filling solutions or vasopressor supports used intraoperatively. On the other hand, we found no significant difference about HR, even though dexmedetomidine is known to have a bradycardic effect [ 14 ]. Moreover, postoperatively, we noticed that patients in the DEX group did not receive more vascular fillings than their counterparts, nor did they require more vasoactive amines. So, we did not observe any delay in intraoperative filling due to the molecule’s hypertensive effect at high doses [ 14 ]. In addition, it seems that patients in the DEX group have a more rapid graft function recovery, illustrated by a greater decrease in postoperative creatinine levels compared with the preoperative baseline, and this, from the first postoperative hour to day 7 of management. In the same way, day 1, day 2, first-week and first-month GFR were also higher in the DEX group. Although the design of this study does not allow us to conclude a causal relationship between dexmedetomidine use and graft function recovery, this finding is nonetheless encouraging, given the rich literature establishing the link between post-transplant serum creatinine and the risk of graft loss. Indeed, in a 1997 study of 510 aKTR from deceased donors, a slow decline in creatinine levels in the first few hours post-transplant was associated with a greater than 10% increased risk of acute graft rejection [ 15 ]. Other teams have demonstrated, in large cohorts of adult patients, the predictive character of creatinine levels at one month [ 16 ], six months, one year [ 17 ] and of the delta of creatinine between six months and one year [ 18 ] on long-term graft survival. Similarly, a study about 6686 children concluded to a higher risk of graft loss at 3 years – with a cumulative risk of around 13M per year – if creatinine clearance was < 50ml/min at one month [ 19 ]. It therefore seems important to us to explore longer-term creatinine levels in our patients, given the clinical impact that such a difference might implies. Recently, studies on dexmedetomidine have multiplied in many medical fields. In the context of nephroprotection, this molecule appears to have pharmacological worthy of attention. Firstly, its hemodynamic stabilizing effect could improve local tissue perfusion [ 1 – 3 ] and limit fibrotic ischemia-reperfusion lesions in transplanted organs [ 4 , 5 , 20 – 27 ]. What’s more, dexmedetomidine might inhibits renin secretion, increasing glomerular filtration and thus kidney excretion of water and sodium [ 4 , 5 ]. Finally, its stimulatory action on the parasympathetic system could confer beneficial anti-inflammatory properties in the peri-surgical context [ 28 ]. The latest available clinical studies show conflicting results in adult patients, with, for example, no significant difference in creatinine clearance after coronary artery bypass surgery [ 29 ] and in the occurrence of postoperative Acute Kidney Injury (AKI) after lung cancer surgery [ 30 ]. Other authors have noted a reduction in post-operative creatinine levels on day 2 of kidney transplantation, but not on day 7 [ 31 ], a lower incidence of DGF [ 11 ], and less AKI after non-cardiac surgery [ 32 ], cardiac surgery [ 8 ] or pediatric cardiac surgery [ 33 ]. In a more nuanced way, a recent meta-analysis found no dexmedetomidine-related difference in DGF and acute graft rejection, but a trend towards a more rapid reduction in serum creatinine and urea [ 34 ]. To our knowledge, there are no pediatric studies related to dexmedetomidine in renal transplantation, and the main evaluation criteria used differ from one author to another. This is why our study sheds new light on the subject, and presents encouraging results for the use of dexmedetomidine in pediatric renal transplantation. Lastly, despite the fact that this drug is available in pediatrics without a marketing authorization (MA), numerous studies insist on its [ 35 – 39 ]. It therefore seems reasonable to use it more widely in children. However, our groups are not entirely comparable on major prognostic criteria for recovery of function [ 40 ]: we observed significantly more living donor transplants in DEX group which may lead to confounding bias, particularly in relation to shorter duration of cold ischemia. Otherwise, this result supports several studies in adult kidney transplant recipient (aKTR) on the influence of intraoperative hemodynamic, and in particular of high MAP, on reducing the risk of DGF [ 41 , 42 ]. The retrospective, single-center nature of our study and its small sample size mean that it is subject to several biases. In particular, a predictive factor of DGF, such as the difference in size between donors and recipients, could not - for lack of data - be taken into account [ 43 ]. Although there was no significant difference at a statistical level, the DEX group included younger patients and more who had benefited from a pre-emptive living-donor transplant than in the no-DEX group. This constitutes a set of good prognostic factors that may have influenced our results on graft function recovery. Moreover, as the patients were not randomized, the use of dexmedetomidine during transplantation was left to the choice of the anesthesiologist, as were the dose infused and other substances delivered during anesthesia. We can also mention the difference in the number of patients on dialysis before transplantation in the two groups, which could distort the interpretation of pre-operative blood volume and serum creatinine in the case of a concomitant dialysis session on the day of transplantation. Furthermore, in contrast to findings in adults, intraoperative arterial hypotension appears to be less associated with the occurrence of postoperative renal injury in children [ 44 , 45 ]. However, no studies specific to pediatric renal transplantation have been carried out to date, and recent studies have focused only on AKI to define the renal impact of hypotension. Moreover, in both anesthesia and intensive care, there is little consensus on the pediatric definition of hypotension, whether for systolic, mean or diastolic values. The most widely used seems to be that of the European Resuscitation Council (ERC) recommendations of 2021 [ 46 ]. But other definitions have been proposed in recent studies [ 47 , 48 ], although anesthetic practices in France have not been standardized in the field of kidney transplantation [ 12 ]. 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Notf Rett Med 24:650–719. https://doi.org/10.1007/s10049-021-00887-9 de Graaff JC, Pasma W, van Buuren S et al (2016) Reference Values for Noninvasive Blood Pressure in Children during Anesthesia: A Multicentered Retrospective Observational Cohort Study. Anesthesiology 125:904–913. https://doi.org/10.1097/ALN.0000000000001310 Michelet D, Brasher C, Marsac L et al (2017) Intraoperative hemodynamic factors predicting early postoperative renal function in pediatric kidney transplantation. Paediatr Anaesth 27:927–934. https://doi.org/10.1111/pan.13201 Tables Table 1. Baseline characteristics Variable no-DEX N = 28 DEX N = 10 p-value Female, N (%) 12 (43) 3 (30) 0.475 Age (years), median [IQR] 14.1 [8.7 ; 16.8] 6.9 [2.7 ; 14.03] 0.144 Weight (kg), median [IQR] 39.1 [20.6 ; 48.8] 20 [13.0 ; 43.2] 0.107 Height (m), median [IQR] 1.47 [1.17 ; 1.68] 1.11 [0.89 ; 1.47] 0.055 Uropathy, N (%) 7 (25) 1 (10) 0.318 Polyuria before transplantation, , N (%) 6 (21) 1 (10) 0.424 Pre-transplantation dialysis, N (%) a 20 (71) 4 (40) 0.077 Pre-transplantation dialysis time (months), median [IQR] 10.5 [0 ; 16.8] 12 [2.3 ; 15.5] 0.994 Second kidney transplantation, N (%) 1 (4) 1 (10) 0.435 Anti-hypertensive therapy before surgery, N (%) 12 (43) 4 (40) 0.875 Living donor, N (%) 5 (18) 5 (50) 0.048 Cold ischemia time (min), median [IQR] 610 [490 ; 801] 327 [173 ; 798] 0.240 Surgery duration (min), median [IQR] 172 [150 ; 195] 160 [134 ; 184] 0.240 Anesthesia duration (min), median [IQR] 253 [230 ; 275] 285 [209 ; 304] 0.274 Continuous variables have been compared using the Mann–Whitney test. Discontinuous variables have been compared using Chi2 test. IQR = interquartile range; kg = kilogram; m = meter; min = minute a peritoneal dialysis or hemodialysis Table 2. intraoperative anesthetic management Variable no-DEX N = 28 DEX N = 10 p-value Total fluid volume (ml/kg), median [IQR] 48 [31 ; 70] 42 [27 ; 98] 0.987 Use of norepinephrine, N (%) 12 (43) 3 (30) 0.475 Total norepinephrine dose (µg/kg), median [IQR] a 11.6 [4.9 ; 23.5] 4.7 [0.1 ; 9.6] 0.233 Use of ephedrine, N (%) 9 (32) 3 (30) 0.900 Total ephedrine dose, median [IQR] a 0.2 [0.1 ; 0.6] 0.3 [0.3 ; 0.4] 0.482 Use of vasoactive drugs a , N (%) 20 (71) 5 (50) 0.220 Continuous variables have been compared using the Mann–Whitney test. Discontinuous variables have been compared using Chi2 test. a only for patients receiving drug b ephedrine, norepinephrine, dobutamine Table 3. Post-surgery evolution Variable no-DEX N = 28 DEX N = 10 p-value Fluid boluses requirement, N (%) 16 (57) 7 (70) 0.475 Total fluid volume (ml/kg), median [IQR] 25 [20 ; 48] 20 [10 ; 30] 0.324 Use of norepinephrine, N (%) 4 (14) 3 (30) 0.271 Use of diuretic (furosemide), N (%) 11 (39) 4 (40) 0.968 Maximal morphinic dose (mg/kg/j), median [IQR] 0.4 [0.2 ; 0.4] 0.4 [0.2 ; 0.5] 0.628 Decreasing blood creatinine ratio, median [IQR] a H1/H0 0.05 [-0.02 ; 0.14] 0.17 [0.08 ; 0.24] 0.008 H24/H0 0.43 [0.15 ; 0.65] 0.82 [0.69 ; 0.89] < 0.001 H48/H0 0.63 [0.26 ; 0.74] 0.87 [0.80 ; 0.93] < 0.001 H168/H0 0.79 [0.66 ; 0.86] 0.92 [0.88 ; 0.95] < 0.001 M1/H0 0.84 [0.73 ; 0.88] 0.92 [0.85 ; 0.95] 0.002 Glomerular Filtration Rate (ml/min/1,73m 2 ), median [IQR] b H24 21.2 [13.8 ; 35.0] 49.0 [20.0 ; 84.1] 0.007 H48 28.8 [19.1 ; 47.6] 78.6 [32.9 ; 112.9] 0.003 H168 58.2 [40.1 ; 85.4] 126.9 [89.9 ; 139.0] < 0.001 M1 74.8 [53.2 ; 87.8] 98.6 [83.0 ; 123.5] 0.009 Delayed Graft Function, N (%) c 3 (11) 0 (0) 0.281 Continuous variables have been compared using the Mann–Whitney test. Discontinuous variables have been compared using Chi2 test. a Obtained by the formula: (blood creatinine at H0 – blood creatinine at Hx) / (blood creatinine at H0). H0 = last pre-surgery biology and Hx = H1, H24, H48 or H168 post-surgery. H is for hour and M is for month. b Obtained by the Schwartz formula 2009 (GFR = 36,5 x height [cm] / blood creatinine [µmol/l]) C Defined as need for dialysis in the first-week post-transplant Supplementary Files GraphicalabstractdexdorMMPedNeph.pptx SupplementarytabledexdorMMPedNeph.docx Cite Share Download PDF Status: Published Journal Publication published 04 Sep, 2024 Read the published version in Pediatric Nephrology → Version 1 posted Editorial decision: Major Revisions Needed 01 Apr, 2024 Reviewers invited by journal 10 Mar, 2024 Reviewers agreed at journal 05 Mar, 2024 First submitted to journal 01 Mar, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4009118","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":276066915,"identity":"c72c76f1-82bb-4f9c-ae95-f81301ed65d4","order_by":0,"name":"Matéo Monteil","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIiWNgGAWjYNACAwsI/bEBRDI2HmCwwauesYHBQIKBgQ3ImtnAIAESOMCQRkgLA0QLMy9YCwMDXi267b3HH3wokIjmn9988LHtDps63fbDQFsS7uHUYnbmXGLjDAOJ3BnH2JKNc8+kSZidSQRpKcat5UaOYTMPUEvDMR4z6dy2wxJmB4BaGH8k4NfyB6hl/jH+b9KWIC3nH4JsIaAFGGK5G47xsEkzgrTcSCSg5cwZw5k9QC0bj6UZG/a2pUluuwG0JQGfluM9Bh9+/LHJnXf48MMHP9ts+M3Opz988AGPFhyAZA2jYBSMglEwClAAAH/iXf87S7xZAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0009-0001-5474-8263","institution":"CHU Nantes: Centre Hospitalier Universitaire de Nantes","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Matéo","middleName":"","lastName":"Monteil","suffix":""},{"id":276066916,"identity":"9eea5c06-7b94-4ee0-9359-9d2084a7abd1","order_by":1,"name":"Alexis Chenouard","email":"","orcid":"","institution":"CHU Nantes: Centre Hospitalier Universitaire de Nantes","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alexis","middleName":"","lastName":"Chenouard","suffix":""},{"id":276066917,"identity":"db2e6eea-54f7-4115-90f7-8aa6da2b22cd","order_by":2,"name":"Gwenaëlle Roussey","email":"","orcid":"","institution":"CHU Nantes: Centre Hospitalier Universitaire de Nantes","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Gwenaëlle","middleName":"","lastName":"Roussey","suffix":""},{"id":276066918,"identity":"27ebb784-7c6d-4bb5-b25a-7a124c4fa035","order_by":3,"name":"Rémi Bernardon","email":"","orcid":"","institution":"CHU Nantes: Centre Hospitalier Universitaire de Nantes","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rémi","middleName":"","lastName":"Bernardon","suffix":""},{"id":276066919,"identity":"3e38707a-c5a2-4c22-bb3d-cc059215a3e9","order_by":4,"name":"Aurélie Gaultier","email":"","orcid":"","institution":"CHU Nantes: Centre Hospitalier Universitaire de Nantes","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Aurélie","middleName":"","lastName":"Gaultier","suffix":""},{"id":276066920,"identity":"9a4077f6-123f-43ad-968b-405944eb6726","order_by":5,"name":"Florence Porcheret","email":"","orcid":"","institution":"CHU Nantes: Centre Hospitalier Universitaire de Nantes","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Florence","middleName":"","lastName":"Porcheret","suffix":""}],"badges":[],"createdAt":"2024-03-03 15:48:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4009118/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4009118/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00467-024-06483-6","type":"published","date":"2024-09-04T16:08:20+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":52105078,"identity":"887f3298-a653-4262-845e-43d317272cd4","added_by":"auto","created_at":"2024-03-06 19:26:36","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":39954,"visible":true,"origin":"","legend":"\u003cp\u003eFlow-chart\u003c/p\u003e\n\u003cp\u003eFig1 was made using \u003cem\u003eMicrosoft Powerpoint\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4009118/v1/abb919a850773bac6fda351d.png"},{"id":52103157,"identity":"a1c08300-f46b-47b2-8ead-af83416f4e73","added_by":"auto","created_at":"2024-03-06 19:18:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":469253,"visible":true,"origin":"","legend":"\u003cp\u003eEvolution of MAP (A) and HR (B) during anesthesia in DEX and no-DEX groups\u003c/p\u003e\n\u003cp\u003e0 min = Anesthetic induction\u003c/p\u003e\n\u003cp\u003eLast PAM and HR measurements = last measurements taken during anesthesia\u003c/p\u003e\n\u003cp\u003eMean values with standard deviation (SD) are shown\u003c/p\u003e\n\u003cp\u003eFig2 was made using \u003cem\u003eGraphPad Prism software\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-4009118/v1/3d1c08db4412312f21f29030.png"},{"id":52103156,"identity":"28a3b304-df2f-4539-bbe6-86e81d5d113f","added_by":"auto","created_at":"2024-03-06 19:18:36","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":630797,"visible":true,"origin":"","legend":"\u003cp\u003eEvolution of blood creatinine from H1 to H168 versus baseline (last blood creatinine before transplantation)\u003c/p\u003e\n\u003cp\u003eGreen points figured living-donor transplants in both groups\u003c/p\u003e\n\u003cp\u003eRed points figured deceased-donor transplants\u003c/p\u003e\n\u003cp\u003eFig3 was made using \u003cem\u003eGraphPad Prism software\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-4009118/v1/2aceca012276456d05f53b23.png"},{"id":64186158,"identity":"470b483a-d05b-4f00-9f84-126c8d3f158b","added_by":"auto","created_at":"2024-09-09 16:25:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1603242,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4009118/v1/9e60702a-e48a-4e92-bc02-4cfc0339df4e.pdf"},{"id":52103154,"identity":"19cbb1d2-2b42-4f39-9169-964a64e0adb3","added_by":"auto","created_at":"2024-03-06 19:18:36","extension":"pptx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":103601,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicalabstractdexdorMMPedNeph.pptx","url":"https://assets-eu.researchsquare.com/files/rs-4009118/v1/5d305a4c2dd475f7e8a7376d.pptx"},{"id":52103152,"identity":"5d81fd65-7719-41b5-8da3-339826dcb4f1","added_by":"auto","created_at":"2024-03-06 19:18:36","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":21608,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementarytabledexdorMMPedNeph.docx","url":"https://assets-eu.researchsquare.com/files/rs-4009118/v1/2195dc614ed94104f3d62d13.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eHaemodynamic Effect of Dexmedetomidine During Pediatric Kidney Transplantation: A Single-Center Retrospective Study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDexmedetomidine is a highly selective alpha-2 agonist mostly used in anesthesia for its sedative properties and its weak respiratory depressant effect. Among its many pharmacological properties we can pick up : hemodynamic stabilization action [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], improved local tissue perfusion [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] and reduced ischemia-reperfusion damage to transplanted organs [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. It also occupies an increasing place in \u003cem\u003eOpioïd-Free Anesthesia\u003c/em\u003e (OFA) strategy as part of \u003cem\u003eEnhanced Recovery After Surgery\u003c/em\u003e (ERAS) protocols [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMany studies and clinical trials have focused on its use in thoracic surgery and heart transplantation and find encouraging data on the positive impact of this molecule on post-operative renal function [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In the field of adult kidney transplant (KT), use of perioperative dexmedetomidine could be associated with a beneficial effect in terms of recovery of graft function [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e–\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], but no data are available to date in pediatrics.\u003c/p\u003e \u003cp\u003eA multicenter study realized in 2017 noted the disparity of anesthesic practices in French pKTR and point the lack of recommendation concerning the use of dexmedetomidine in this context [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Yet, since 2019 at the pediatric University Hospital of Nantes, the dexmedetomidine is increasingly used in perioperative anesthesic protocol of KT.\u003c/p\u003e \u003cp\u003eThus, in this pilot study, we aimed to assess retrospectively the intraoperative hemodynamic effect of an anesthesic protocol with dexmedetomidine (DEX group) compared with a protocol without dexmedetomidine (no-DEX group) in pKTR.\u003c/p\u003e"},{"header":"MATERIALS ET METHODS","content":"\u003cp\u003eII.1. Study population and design\u003c/p\u003e\n\u003cp\u003eThis single-center, retrospective, observational study was conducted at Nantes University Hospital, a tertiary children’s hospital. It was approved by the local Research Ethics Board of the University of Nantes, France on April 2023 (N°23-54-04-190). The requirement for parental informed consent was waived.\u003c/p\u003e\n\u003cp\u003eAll children, aged less than 18 years old, hospitalized for a KT in Nantes pediatric hospital between January 2019 and June 2023 were eligible. Patients without intra-operative hemodynamic data recording were excluded \u003cem\u003e(Figure 1)\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFig1\u003c/strong\u003e Flow-chart \u003c/p\u003e\n\u003cp\u003eFig1 was made using \u003cem\u003eMicrosoft Powerpoint\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe compared patients who received dexmedetomidine intraoperatively (DEX group) and those who did not (no-DEX group).\u003c/p\u003e\n\u003cp\u003eII.2. Anesthesic protocol\u003c/p\u003e\n\u003cp\u003eAll pKTR received anesthesia and monitoring according to local protocols. Choice of sedative agents used was left to discretion of the anesthesiologist in charge of the patient. \u003c/p\u003e\n\u003cp\u003eIn the group without dexmedetomidine (no-DEX), induction was performed by intravenous way with propofol or thiopenthal combined with morphinic (sufentanil or remifentanil), or by a combination of inhalatory and intravenous way with sevoflurane and sufentanil. Maintenance anesthesia was provided by morphinic (sufentanil or remifentanil) and sevoflurane, which could be associated with propofol.\u003c/p\u003e\n\u003cp\u003eIn the dexmedetomidine group (DEX), induction was assumed by dexmedetomidine and/or propofol with or without sufentanil or by sevoflurane and dexmedetomidine. Maintenance included dexmedetomidine and sevoflurane, sometimes combined with sufentanil or propofol.\u003c/p\u003e\n\u003cp\u003eIn both groups, patients were curarized by atracurium throughout the anesthesia.\u003c/p\u003e\n\u003cp\u003eBecause the dexmedetomidine administration protocol was not clearly defined, each child received a variable dose of medication by continuous intravenous route ranging from 0,7 to 1,4 µg/kg/h after a loading dose. Patient impregnation with the drug was assessed empirically by the anesthesiologist after a drop in heart rate on the continuous monitoring occurs. Dexmedetomidine infusion was stopped on arrival in Intensive Care Unit (ICU).\u003c/p\u003e\n\u003cp\u003eII.3. Collected data\u003c/p\u003e\n\u003cp\u003eWe collected hemodynamic data for each patient during all transplant surgery thanks to anesthesia software available at our hospital: \u003cem\u003ePégase\u003c/em\u003e and \u003cem\u003eAnesthesia\u003c/em\u003e \u003cem\u003eConsultation\u003c/em\u003e. Vital constants of interest (MAP and HR) were recorded every 5 minutes throughout the duration of anesthesia (\u003cem\u003ei.e.\u003c/em\u003e from anesthesic induction to the arrival in post-operative recovery room).\u003c/p\u003e\n\u003cp\u003eWe have also recorded the intraoperative hemodynamic status by use and total doses, relative to weight, of vasoactive drugs (norepinephrine, dobutamine and ephedrine) and vascular filling solutions (ringer lactate, serum saline, albumin 4%) required during anesthesia; and the immediate postoperative hemodynamic status (less than 24 hours), through need of hemodynamic support like vasopressor drugs (norepinephrine), vascular filling solutions or use of diuretics (furosemide)\u003c/p\u003e\n\u003cp\u003eThe graft function recovery was assessed by decreasing of serum creatinine (via a serum creatinine decline ratio at hour 0 (H0), corresponding to last pre-transplantation serum creatinine, versus H1, H24, H48, H168; the glomerular filtration rate (GFR) at H24, H48, H168 and at the end of first month); and the onset of delayed graft function (DGF), defined as the need of dialysis during first week post-transplant. GFR was calculated with Schwartz formula 2009 : GFR = 36.5 x (height [cm] / serum creatinine [µmol/L]) [13].\u003c/p\u003e\n\u003cp\u003eWe collected the mean vascular resistance index of the graft, assessed on the first renal ultrasound-doppler. \u003c/p\u003e\n\u003cp\u003eThe postoperative analgesia quality was assessed by the maximum dose of morphine used (continuous flow rate expressed in mg/kg/day).\u003c/p\u003e\n\u003cp\u003eEpidemiological and clinical data and biological results were extracted from paper and computerized patient files (\u003cem\u003ePowerchart\u003c/em\u003e software). Other data were extracted from organ donor records available on the \u003cem\u003eagence de la biomédecine\u003c/em\u003e (\u003cem\u003eABM\u003c/em\u003e) national registry.\u003c/p\u003e\n\u003cp\u003eII.4. Statistical analysis \u003c/p\u003e\n\u003cp\u003eContinuous data were presented as median value with interquartile ranges (25\u003csup\u003eth\u003c/sup\u003e and 75\u003csup\u003eth\u003c/sup\u003e percentiles) and categorical data as number and percentage. Comparisons of continuous and categorical data between the 2 groups (DEX and no-DEX) were performed by using the non-parametric Mann Whitney and Chi2 tests, respectively. \u003c/p\u003e\n\u003cp\u003eTo account the repeated measurements of MAP and HR variables, a linear mixed model on longitudinal data adjusted for the random effect of each patient was used for the comparison between groups. This model was also adjusted for age, group and anesthesia duration. A p-value less than 0.05 was considered significant.\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed using R software (version 4.2.1) and GraphPad Prism (version 8.0.2).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eIII.1. Participants\u003c/p\u003e\n\u003cp\u003eBetween January 2015 and June 2023, 38 patients were included for this study. 28 received an anesthetic protocol without dexmedetomidine (no-DEX group) and 10 with dexmedetomidine (DEX group) (\u003cem\u003eFigure 1\u003c/em\u003e). \u003c/p\u003e\n\u003cp\u003eBaseline characteristics and data likely to influence graft prognosis in both groups are presented in \u003cem\u003eTable 1. \u003c/em\u003eMedian age of DEX group patients was 6.9 years versus 14.1 years in no-DEX group (\u003cem\u003ep = 0.144\u003c/em\u003e). Median duration of cold ischemia was respectively of 327 minutes and 610 minutes in DEX and no-DEX groups (\u003cem\u003ep = 0.240\u003c/em\u003e). There was 50% of living-donor transplant in DEX group versus 18% in no-DEX group (\u003cem\u003ep = 0.048)\u003c/em\u003e. We found no significant differences between the two groups for the other selected criteria.\u003c/p\u003e\n\u003cp\u003eIII.2. Hemodynamic effect\u003c/p\u003e\n\u003cp\u003eEvolution of MAP and HR during anesthesia is shown in \u003cem\u003eFigure 2\u003c/em\u003e. Intraoperative MAP was significantly higher in DEX group compared to no-DEX group, independently of patient age and anesthesia duration (mean difference + 8 [IQR: 2-14] mmHg, \u003cem\u003ep = 0.034\u003c/em\u003e). No difference was observed concerning the HR in the 2 groups (\u003cem\u003ep = 0.787\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFig\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e Evolution of MAP (A) and HR (B) during anesthesia in DEX and no-DEX groups\u003c/p\u003e\n\u003cp\u003e0 min = Anesthetic induction \u003c/p\u003e\n\u003cp\u003eLast PAM and HR measurements = last measurements taken during anesthesia\u003c/p\u003e\n\u003cp\u003eMean values with standard deviation (SD) are shown\u003c/p\u003e\n\u003cp\u003eFig2 was made using \u003cem\u003eGraphPad Prism software\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn addition, we observed no significant difference between the 2 groups in the quantity of vascular filling fluids delivered, nor in the use of vasoactive drugs (norepinephrine, ephedrine, dobutamine) (\u003cem\u003eTable 2\u003c/em\u003e). \u003c/p\u003e\n\u003cp\u003ePostoperative needs in terms of vascular filling, vasoactive amines or diuretics were equivalent in both groups (\u003cem\u003eTable 3\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003eIII.3. Graft function recovery\u003c/p\u003e\n\u003cp\u003eWe observed a statistically significant greater serum creatinine decline ratio from H1 to H168 in the DEX group compared with the no-DEX group (H1: \u003cem\u003ep = 0.008\u003c/em\u003e; H168: \u003cem\u003ep \u0026lt; 0.001)\u003c/em\u003e. For example, at H1, median creatinine decreased by 17% in the DEX group versus 5% in the no-DEX group. GFR at H24, H48, H168 and one month post-transplant were also significantly higher in the DEX group (\u003cem\u003ep \u0026lt; 0.001\u003c/em\u003e at H168). These results are illustrated in \u003cem\u003eTable 3 \u003c/em\u003eand \u003cem\u003eFigure 3\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFig\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e Evolution of blood creatinine from H1 to H168 versus baseline (last blood creatinine before transplantation)\u003c/p\u003e\n\u003cp\u003eGreen points figured living-donor transplants in both groups\u003c/p\u003e\n\u003cp\u003eRed points figured deceased-donor transplants\u003c/p\u003e\n\u003cp\u003eFig3 was made using \u003cem\u003eGraphPad Prism software\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThere was no statistical difference between groups regarding DGF (\u003cem\u003ep = 0.281\u003c/em\u003e). \u003c/p\u003e\n\u003cp\u003eData for living and deceased donors pKTR are available in \u003cem\u003esupplementary 1 \u003c/em\u003eand \u003cem\u003esupplementary 2\u003c/em\u003e. \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this pilot retrospective study, the use of dexmedetomidine as a continuous infusion for anesthesia in children with KT was associated with a perioperative higher MAP, compared with anesthesia without this molecule.\u003c/p\u003e \u003cp\u003eThis observation does not seem to be related to a different management of hemodynamic support between the 2 groups. Indeed, we observed no differences regarding quantities of vascular filling solutions or vasopressor supports used intraoperatively. On the other hand, we found no significant difference about HR, even though dexmedetomidine is known to have a bradycardic effect [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMoreover, postoperatively, we noticed that patients in the DEX group did not receive more vascular fillings than their counterparts, nor did they require more vasoactive amines. So, we did not observe any delay in intraoperative filling due to the molecule\u0026rsquo;s hypertensive effect at high doses [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition, it seems that patients in the DEX group have a more rapid graft function recovery, illustrated by a greater decrease in postoperative creatinine levels compared with the preoperative baseline, and this, from the first postoperative hour to day 7 of management. In the same way, day 1, day 2, first-week and first-month GFR were also higher in the DEX group.\u003c/p\u003e \u003cp\u003eAlthough the design of this study does not allow us to conclude a causal relationship between dexmedetomidine use and graft function recovery, this finding is nonetheless encouraging, given the rich literature establishing the link between post-transplant serum creatinine and the risk of graft loss. Indeed, in a 1997 study of 510 aKTR from deceased donors, a slow decline in creatinine levels in the first few hours post-transplant was associated with a greater than 10% increased risk of acute graft rejection [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Other teams have demonstrated, in large cohorts of adult patients, the predictive character of creatinine levels at one month [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], six months, one year [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and of the delta of creatinine between six months and one year [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] on long-term graft survival. Similarly, a study about 6686 children concluded to a higher risk of graft loss at 3 years \u0026ndash; with a cumulative risk of around 13M per year \u0026ndash; if creatinine clearance was \u0026lt;\u0026thinsp;50ml/min at one month [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. It therefore seems important to us to explore longer-term creatinine levels in our patients, given the clinical impact that such a difference might implies.\u003c/p\u003e \u003cp\u003eRecently, studies on dexmedetomidine have multiplied in many medical fields. In the context of nephroprotection, this molecule appears to have pharmacological worthy of attention. Firstly, its hemodynamic stabilizing effect could improve local tissue perfusion [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] and limit fibrotic ischemia-reperfusion lesions in transplanted organs [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21 CR22 CR23 CR24 CR25 CR26\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. What\u0026rsquo;s more, dexmedetomidine might inhibits renin secretion, increasing glomerular filtration and thus kidney excretion of water and sodium [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Finally, its stimulatory action on the parasympathetic system could confer beneficial anti-inflammatory properties in the peri-surgical context [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe latest available clinical studies show conflicting results in adult patients, with, for example, no significant difference in creatinine clearance after coronary artery bypass surgery [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] and in the occurrence of postoperative Acute Kidney Injury (AKI) after lung cancer surgery [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Other authors have noted a reduction in post-operative creatinine levels on day 2 of kidney transplantation, but not on day 7 [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], a lower incidence of DGF [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and less AKI after non-cardiac surgery [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], cardiac surgery [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] or pediatric cardiac surgery [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In a more nuanced way, a recent meta-analysis found no dexmedetomidine-related difference in DGF and acute graft rejection, but a trend towards a more rapid reduction in serum creatinine and urea [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo our knowledge, there are no pediatric studies related to dexmedetomidine in renal transplantation, and the main evaluation criteria used differ from one author to another. This is why our study sheds new light on the subject, and presents encouraging results for the use of dexmedetomidine in pediatric renal transplantation.\u003c/p\u003e \u003cp\u003eLastly, despite the fact that this drug is available in pediatrics without a marketing authorization (MA), numerous studies insist on its [\u003cspan additionalcitationids=\"CR36 CR37 CR38\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. It therefore seems reasonable to use it more widely in children.\u003c/p\u003e \u003cp\u003eHowever, our groups are not entirely comparable on major prognostic criteria for recovery of function [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]: we observed significantly more living donor transplants in DEX group which may lead to confounding bias, particularly in relation to shorter duration of cold ischemia.\u003c/p\u003e \u003cp\u003eOtherwise, this result supports several studies in adult kidney transplant recipient (aKTR) on the influence of intraoperative hemodynamic, and in particular of high MAP, on reducing the risk of DGF [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe retrospective, single-center nature of our study and its small sample size mean that it is subject to several biases. In particular, a predictive factor of DGF, such as the difference in size between donors and recipients, could not - for lack of data - be taken into account [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Although there was no significant difference at a statistical level, the DEX group included younger patients and more who had benefited from a pre-emptive living-donor transplant than in the no-DEX group. This constitutes a set of good prognostic factors that may have influenced our results on graft function recovery. Moreover, as the patients were not randomized, the use of dexmedetomidine during transplantation was left to the choice of the anesthesiologist, as were the dose infused and other substances delivered during anesthesia. We can also mention the difference in the number of patients on dialysis before transplantation in the two groups, which could distort the interpretation of pre-operative blood volume and serum creatinine in the case of a concomitant dialysis session on the day of transplantation.\u003c/p\u003e \u003cp\u003eFurthermore, in contrast to findings in adults, intraoperative arterial hypotension appears to be less associated with the occurrence of postoperative renal injury in children [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. However, no studies specific to pediatric renal transplantation have been carried out to date, and recent studies have focused only on AKI to define the renal impact of hypotension. Moreover, in both anesthesia and intensive care, there is little consensus on the pediatric definition of hypotension, whether for systolic, mean or diastolic values. The most widely used seems to be that of the European Resuscitation Council (ERC) recommendations of 2021 [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. But other definitions have been proposed in recent studies [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e], although anesthetic practices in France have not been standardized in the field of kidney transplantation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn conclusion, this preliminary study suggests that the use of intraoperative dexmedetomidine in pediatric renal transplantation provide higher perioperative MAP compared to use of other sedative agents. It may promote better recovery of graft function. These initial findings would need to be confirmed by a multicenter randomized controlled trial before new recommendations in this field could be considered.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors have no competing interests to declare that are relevant to the content of this article.\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u003c/h2\u003e \u003cp\u003eWe want to thanks Orkid (Orphan Kidney Disease) for his support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLiu X, Li Y, Kang L, Wang Q (2021) Recent Advances in the Clinical Value and Potential of Dexmedetomidine. 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Baseline characteristics\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003eVariable\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003eno-DEX\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eN = 28\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003eDEX\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eN = 10\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003eFemale, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e12 (43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e3 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.475\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003eAge (years), median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e14.1 [8.7 ; 16.8]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e6.9 [2.7 ; 14.03]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.144\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003eWeight (kg),\u0026nbsp;median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e39.1 [20.6 ; 48.8]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e20 [13.0 ; 43.2]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.107\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003eHeight (m),\u0026nbsp;median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e1.47 [1.17 ; 1.68]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e1.11 [0.89 ; 1.47]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.055\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003eUropathy, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e7 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e1 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.318\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003ePolyuria before transplantation,\u0026nbsp;, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e6 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e1 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.424\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003ePre-transplantation dialysis, N (%) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e20 (71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e4 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.077\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003ePre-transplantation dialysis time (months),\u0026nbsp;median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e10.5 [0 ; 16.8]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e12 [2.3 ; 15.5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.994\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003eSecond kidney transplantation, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e1 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e1 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.435\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003eAnti-hypertensive therapy before surgery, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e12 (43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e4 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.875\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003eLiving donor, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e5 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e5 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.048\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003eCold ischemia time (min), median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e610 [490 ; 801]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e327 [173 ; 798]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.240\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003eSurgery duration (min), median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e172 [150 ; 195]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e160 [134 ; 184]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.240\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.288557213930346%\"\u003e\n \u003cp\u003eAnesthesia duration (min), median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e253 [230 ; 275]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e285 [209 ; 304]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23714759535655%\"\u003e\n \u003cp\u003e\u003cem\u003e0.274\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cem\u003eContinuous variables have been compared using the Mann\u0026ndash;Whitney test. Discontinuous variables have been compared using Chi2 test.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eIQR = interquartile range; kg = kilogram; m = meter; min = minute\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u003csup\u003ea \u0026nbsp;\u003c/sup\u003e\u003c/em\u003e\u003cem\u003eperitoneal dialysis or hemodialysis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eTable 2. intraoperative anesthetic management\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"609\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.19078947368421%\" style=\"width: 36.1983%;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003eno-DEX\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eN = 28\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003eDEX\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eN = 10\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 8.8587%;\"\u003e\n \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.19078947368421%\" style=\"width: 36.1983%;\"\u003e\n \u003cp\u003eTotal fluid volume (ml/kg), median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003e48 [31 ; 70]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003e42 [27 ; 98]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 8.8587%;\"\u003e\n \u003cp\u003e\u003cem\u003e0.987\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.19078947368421%\" style=\"width: 36.1983%;\"\u003e\n \u003cp\u003eUse of norepinephrine, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003e12 (43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003e3 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 8.8587%;\"\u003e\n \u003cp\u003e\u003cem\u003e0.475\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.19078947368421%\" style=\"width: 36.1983%;\"\u003e\n \u003cp\u003eTotal norepinephrine dose (\u0026micro;g/kg), median [IQR] \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003e11.6 [4.9 ; 23.5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003e4.7 [0.1 ; 9.6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 8.8587%;\"\u003e\n \u003cp\u003e\u003cem\u003e0.233\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.19078947368421%\" style=\"width: 36.1983%;\"\u003e\n \u003cp\u003eUse of ephedrine, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003e9 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003e3 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 8.8587%;\"\u003e\n \u003cp\u003e\u003cem\u003e0.900\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.19078947368421%\" style=\"width: 36.1983%;\"\u003e\n \u003cp\u003eTotal ephedrine dose, median [IQR] \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003e0.2 [0.1 ; 0.6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003e0.3 [0.3 ; 0.4]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 8.8587%;\"\u003e\n \u003cp\u003e\u003cem\u003e0.482\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.19078947368421%\" style=\"width: 36.1983%;\"\u003e\n \u003cp\u003eUse of vasoactive drugs \u003csup\u003ea\u003c/sup\u003e, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003e20 (71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 12.8926%;\"\u003e\n \u003cp\u003e5 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.269736842105264%\" style=\"width: 8.8587%;\"\u003e\n \u003cp\u003e\u003cem\u003e0.220\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"99.17898193760263%\" colspan=\"4\" style=\"width: 74.5041%;\"\u003e\n \u003cp\u003e\u003cem\u003eContinuous variables have been compared using the Mann\u0026ndash;Whitney test. Discontinuous variables have been compared using Chi2 test.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/em\u003e\u003cem\u003e\u0026nbsp;only for patients receiving drug\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u003csup\u003eb\u003c/sup\u003e\u003c/em\u003e\u003cem\u003e\u0026nbsp;ephedrine, norepinephrine, dobutamine\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eTable 3. Post-surgery evolution\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003eno-DEX\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eN = 28\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003eDEX\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eN = 10\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eFluid boluses requirement, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e16 (57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e7 (70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e0.475\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eTotal fluid volume (ml/kg), median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e25 [20 ; 48]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e20 [10 ; 30]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e0.324\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eUse of norepinephrine, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e4 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e3 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e0.271\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eUse of diuretic (furosemide), N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e11 (39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e4 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e0.968\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eMaximal morphinic dose (mg/kg/j), median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.4 [0.2 ; 0.4]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.4 [0.2 ; 0.5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e0.628\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\"\u003e\n \u003cp\u003eDecreasing blood creatinine ratio, median [IQR] \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eH1/H0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.05 [-0.02 ; 0.14]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.17 [0.08 ; 0.24]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e0.008\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eH24/H0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.43 [0.15 ; 0.65]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.82 [0.69 ; 0.89]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt; 0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eH48/H0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.63 [0.26 ; 0.74]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.87 [0.80 ; 0.93]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt; 0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eH168/H0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.79 [0.66 ; 0.86]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.92 [0.88 ; 0.95]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt; 0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eM1/H0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.84 [0.73 ; 0.88]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.92 [0.85 ; 0.95]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e0.002\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\"\u003e\n \u003cp\u003eGlomerular Filtration Rate (ml/min/1,73m\u003csup\u003e2\u003c/sup\u003e), median [IQR] \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eH24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e21.2 [13.8 ; 35.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e49.0 [20.0 ; 84.1]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e0.007\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eH48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e28.8 [19.1 ; 47.6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e78.6 [32.9 ; 112.9]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e0.003\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eH168\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e58.2 [40.1 ; 85.4]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e126.9 [89.9 ; 139.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt; 0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eM1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e74.8 [53.2 ; 87.8]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e98.6 [83.0 ; 123.5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e0.009\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40%\"\u003e\n \u003cp\u003eDelayed Graft Function, N (%) \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e3 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003e0.281\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cem\u003eContinuous variables have been compared using the Mann\u0026ndash;Whitney test. Discontinuous variables have been compared using Chi2 test.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/em\u003e\u003cem\u003e\u0026nbsp;Obtained by the formula: (blood creatinine at H0 \u0026ndash; blood creatinine at Hx) / (blood creatinine at H0). H0 = last pre-surgery biology and Hx = H1, H24, H48 or H168 post-surgery. H is for hour and M is for month.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u003csup\u003eb\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e\u003cem\u003eObtained by the Schwartz formula 2009 (GFR = 36,5 x height [cm] / blood creatinine [\u0026micro;mol/l])\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u003csup\u003eC\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e\u003cem\u003eDefined as need for dialysis in the first-week post-transplant\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"dexmedetomidine, kidney transplant, hemodynamic, pediatric, mean arterial pressure, graft function","lastPublishedDoi":"10.21203/rs.3.rs-4009118/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4009118/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDexmedetomidine is increasingly used for its hemodynamic stability property during general anesthesia. However, there is no data on pediatric kidney transplant recipients (pKTR). Our study investigates the hemodynamic effect of perioperatively administered dexmedetomidine in pKTR.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eBetween 2019 and 2023, all pKTR below 18 years were studied retrospectively at Nantes University Hospital. Intraoperative hemodynamic status was compared between patients who had received dexmedetomidine during kidney transplantation (DEX group) and patients who had not (no-DEX group). Mean arterial pressure (MAP) and heart rate (HR) were monitored throughout the duration of anesthesia and compared. Graft function was assessed by creatinine levels and Glomerular Filtration Rate (GFR) at specific time points. The use of fluid and vasoactive drugs peri-operatively and within 24 hours after surgery was also studied.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e38 patients were included, 10 in the DEX group et 28 in the no-DEX group. Intraoperative HR was similar between the two groups; however, MAP was significantly higher (mean difference 8, standard deviation [SD: 2\u0026ndash;14] mmHg, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0,034\u003c/em\u003e) in the DEX group. No differences were found regarding the use of fluid and vasoactive drug therapy between groups. Glomerular filtration rate at one month was significantly higher in DEX group (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0,009\u003c/em\u003e).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eChildren receiving intraoperative dexmedetomidine during a KT presented higher perioperative MAP compare to children receiving other sedative agents. DEX group also showed better graft function at one month. The direct impact of dexmedetomidine on immediate post-operative graft function in pTKR should be studied in a prospective multicenter randomized study.\u003c/p\u003e","manuscriptTitle":"Haemodynamic Effect of Dexmedetomidine During Pediatric Kidney Transplantation: A Single-Center Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-06 19:18:31","doi":"10.21203/rs.3.rs-4009118/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revisions Needed","date":"2024-04-01T13:48:09+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-10T19:02:18+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-03-05T17:58:28+00:00","index":0,"fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2024-03-01T09:33:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"6dfa1045-69c7-4746-abb4-3d7ba26353d3","owner":[],"postedDate":"March 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-09T16:17:03+00:00","versionOfRecord":{"articleIdentity":"rs-4009118","link":"https://doi.org/10.1007/s00467-024-06483-6","journal":{"identity":"pediatric-nephrology","isVorOnly":false,"title":"Pediatric Nephrology"},"publishedOn":"2024-09-04 16:08:20","publishedOnDateReadable":"September 4th, 2024"},"versionCreatedAt":"2024-03-06 19:18:31","video":"","vorDoi":"10.1007/s00467-024-06483-6","vorDoiUrl":"https://doi.org/10.1007/s00467-024-06483-6","workflowStages":[]},"version":"v1","identity":"rs-4009118","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4009118","identity":"rs-4009118","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}