How to follow the guidelines, when the appropriate fluid is missing?

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David W. Brossier, Isabelle Goyer, Claire Morice, Fahad Alsohime, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3892154/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Mar, 2024 Read the published version in European Journal of Pediatrics → Version 1 posted 7 You are reading this latest preprint version Abstract Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. Recently paediatric societies have produced evidence-based practice guidelines that recommend the use of balanced isotonic fluid when prescribing IV-MFT in both acute and critical paediatric care. Unfortunately, the applicability of these guidelines could be called into question when a ready-to-use glucose containing balanced isotonic fluid is not available. The main objective of this study was to describe the availability of glucose containing balanced isotonic fluids in European and Middle Eastern paediatric acute and critical care settings. This work is an ancillary study of the survey dedicated to IV-MFT practices in the paediatric acute and critical care settings in Europe and Middle East, a cross-sectional electronic 27-item survey, emailed in April–May 2021 to paediatric critical care physicians across 34 European and Middle East countries. The survey was developed by an expert multi-professional panel within the European Society of Peadiatric and Neonatal Intensive Care (ESPNIC). Balanced Isotonic Fluid with glucose 5% was available for only 32/153 (21%) responders. Balanced Isotonic Fluid with glucose 5% was consistently available in the United Kingdom (90%) but not available in France, Greece, The Netherlands and Turkey. Ready-to-use isotonic balanced IV solutions containing glucose in sufficient amount exist, but are inconsistently available through Europe. National and European Medication Safety Incentives should guarantee availability of the most appropriate and safest IV-MFT solution for all children. Intravenous fluids Balanced fluids Isotonic Fluids Figures Figure 1 What is Known • Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. • Balanced isotonic fluid is recommended when prescribing IV-MFT in both acute and critical paediatric care. What is New: • Balanced isotonic fluid with glucose 5% is available for less than 25% of the prescribers in Europe and Middle East. • Availability of balanced isotonic fluid with glucose 5% varies from one country to another but can also be inconsistent within the same country. • Clinicians who have access to a ready-to-use balanced isotonic fluid with glucose 5% are more likely to consider its use than clinicians who do not have access to such an IV solution. Introduction Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care ( 1 ). It has been used for more than a century and yet, it’s only recently that paediatric societies have produced evidence-based practice guidelines to guide the use of IV fluids in clinical practice ( 2 , 3 ). These guidelines recommend the use of balanced isotonic fluid when prescribing IV-MFT in both acute and critical paediatric care. It is also recommended to provide the appropriate amounts of potassium and glucose to prevent children from presenting hypokalaemia and hypoglycaemia ( 2 , 3 ). However, even though two international paediatric societies (the American Academic of Pediatrics (AAP) ( 2 ) and the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) ( 3 )) are to be commended for these long-awaited guidelines, the applicability and implementation of these guidelines is threatened by a lack of these fluids available. During the last decade, the growing interest in the use of balanced crystalloids to prevent patients from developing clinical complications and mortality related to hyperchloremia and metabolic acidosis, has been associated with a growing availability of balanced IV fluids ( 4 ). Unfortunately, amongst this variety of available balanced IV fluids, very few, or even none in certain countries, contain glucose. However, glucose content is fundamental for paediatric IV-MFT. In 2022, Morice et al. showed that the absence of glucose in the solution was the main reason for not prescribing a balanced fluid by 29.4% of the respondents ( 1 ). The main objective of this study was to describe the availability of glucose containing balanced isotonic fluids in European and Middle Eastern paediatric acute and critical care settings, performing a complementary analysis of Morice et al. 2022 survey. The secondary objective was to evaluate the impact of the absence of paediatric appropriate ready-to-use fluids on IV-MFT declarative practice. Materials and method This work was an ancillary study of the survey dedicated to IV-MFT practice in the paediatric acute and critical care settings in 34 countries in Europe and Middle East ( 1 ). The study design, the included population and the survey instrument development, content and data collection have previously been published ( 1 ). Data analysis Data were analysed according to the country of the responders and according to the availability of balanced isotonic fluids, with or without glucose 5%. The data analysis was focused on the questions related to the use of balanced fluids (Q13,14,15,16) and fluid choices (Q17,18,19,20). We used a summative score to summarize the results from Likert scale questions for each participant. Variables distributions were assessed by the Shapiro–Wilk comparison test and continuous variables were presented as median [min-max]. Categorical variables were presented as number (percentage). Comparisons between both groups were made by a Mann–Whitney U test or a Kruskal-Wallis’s test for continuous variables as appropriate and by a Chi-square test with Monte Carlo simulation with 2000 replicates for categorical variables. The level of statistical significance was set at P < 0.05. Statistical analyses were performed using open-access R software (Version 4.2.1; R Foundation for Statistical Computing, Vienna, Austria). Ethical approval was obtained from Caen-France institutional review board (reference number 2474). Results Participants’ characteristics Participants’ characteristics were presented in ( 1 ). The response rate of this survey was considered above 60%, with 153 centres represented. One participant was excluded for practicing in Australia. Fluid availability according to country Fluid availability according to the country of the responders is presented in Table 1 . Balanced Isotonic Fluid with glucose 5% was declared available for only 32 (21%) responders. Balanced Isotonic Fluid with glucose 5% was consistently available only in the United Kingdom (90%) and totally absent from France, Greece, The Netherlands and Turkey. The most widely available fluids were balanced (93.5%) and unbalanced (87.6%) isotonic fluids without glucose. Table 1 Fluid availability in Europe and Middle East Total Belgium France Germany Greece Italy Poland Portugal Spain Switzerland The Netherlands Turkey United Kingdom Others p n = 153 n = 7 n = 17 n = 10 n = 5 n = 10 n = 9 n = 7 n = 19 n = 11 n = 5 n = 9 n = 10 n = 34 Balanced Isotonic Fluid 143 (93.5%) 6 (85.7%) 15 (88.2%) 8 (80%) 5 (100%) 10 (100%) 9 (100%) 7 (100%) 17 (89.5%) 11 (100%) 5 (100%) 8 (88.9%) 10 (100%) 32 (94.1%) 0.68 Balanced Isotonic Fluid with glucose 5% 32 (21.0%) 4 (57.1%) 0 2 (20.0%) 0 1 (10.0%) 1 (11.1%) 3 (42.9%) 4 (21.1%) 3 (27.3%) 0 0 9 (90%) 5 (14.7%) < 0.0001 Balanced Isotonic Fluid with glucose 1% 23 (15.0%) 0 8 (47.1%) 3 (30%) 0 0 6 (66.7%) 0 1 (5.3%) 4 (36.4%) 0 0 0 1 (2.9%) < 0.0001 Balanced Hypotonic Fluid with glucose 5% 4 (2.6%) 1 (14.3%) 0 0 0 2 (20%) 0 0 0 0 0 0 0 1 (2.9%) 0.10 Unbalanced Isotonic Fluid 134 (87.6%) 6 (85.7%) 14 (82.4%) 6 (60%) 5 (100%) 10 (100%) 5 (55.6%) 7 (100%) 17 (89.5%) 10 (90.9%) 4 (80%) 9 (100%) 10 (100%) 31 (91.2%) 0.03 Unbalanced Isotonic Fluid with glucose 5% 7 (4.6%) 1 (14.3%) 0 0 0 0 0 1 (14.3%) 4 (21.1%) 0 0 0 1 (10%) 0 0.06 Unbalanced Hypotonic Fluid with glucose 5% 114 (74.5%) 6 (85.7%) 17 (100%) 6 (60%) 4 (80%) 4 (40%) 3 (33.3%) 7 (100%) 14 (73.7%) 7 (63.6%) 4 (80%) 9 (100%) 9 (90%) 24 (70.6%) 0.001 - Balanced Isotonic Fluid are: Ringer’s lactate, Ringer’s acetate, Hartamann’s solution, Plasmalyte, Isolyte E & S, Normosol R, Isofundine, Sterofundine, Ringerfundine, Optilyte - Balanced Isotonic Fluid with glucose 5% are: PlasmalyteG5, Sterofundine VG5 - Balanced Isotonic Fluid with glucose 1% are: Isopedia, Benelyte - Balanced Hypotonic Fluid with glucose 5% are: Normosol M, Sterofundine HEG 5, Isolyte G,M & P. - Unbalanced Isotonic Fluid is: NaCl 0.9% - Unbalanced Isotonic Fluid with glucose 5% is: G5NaCl0.9% - Unbalanced Hypotonic Fluid with glucose 5% are: Glucidion, Osmotan, Bionolyte, Polyionique, Dextrion. Impact of country on prescription practices Responders’ consideration for the importance of balanced fluids varies considerably between countries in both conventional and critical care unit (SDC 1). Prescription practices varied considerably between countries (SDC 1). Balanced isotonic fluid was considered in 45.0% of the clinical situations (from 6.5% in Greece to 83.3% in Poland) and unbalanced isotonic fluid in 42.8% (from 11.1% in Poland to 78.5% in Turkey). Hypotonic unbalanced fluid was considered in 10.5% of the clinical situations (from 0% in the UK to 30% in Greece). It was consistently the less prescribed fluid, except in France and in Greece, where it was prescribed more than balanced isotonic fluid. Impact of fluid availability on prescriptions’ practices Among the 32 responders who declared having access to a balanced isotonic fluid with glucose 5%, 23 (71.9%) reported that balanced isotonic fluid should be always considered vs 42/121 (34.7%) (p < 0.001) in the case of unavailability of a balanced isotonic fluid with glucose 5% (SDC 2). The availability of a balanced isotonic fluid with glucose 5% was systematically and significantly associated with a preference for prescribing this fluid over unbalanced isotonic or hypotonic crystalloids, notwithstanding the clinical situation studied (SDC 2). Discussion Performing a complementary analysis on the declarative data of Morice et al. 2022 survey ( 1 ), focusing on the declared type of available IV fluids, we have realized that only 21% of responders have access to a commercialized balanced isotonic fluid containing 5% glucose, which is considered as the current recommended IV fluid for paediatric IV-MFT. We have shown that the availability of such a solution varies from one country to another but can also be inconsistent within the same country. In addition, we have observed that the availability of a balanced isotonic fluid with 5% glucose was associated with a higher declarative use of balanced isotonic fluid in almost all the assessed clinical situations. This inconsistency regarding the availability of these ready-made balanced solutions are a significant barrier to the implementation of the recent ESPNIC IV-MFT guidelines into clinical practices and could explain the obsolete but still current use of hypotonic IV fluids ( 1 , 5 ). This should be reassessed once a specific model for disseminating these guidelines in clinical practice has been implemented. In the absence of a ready-to-use appropriate IV fluid for children, local compounding to make solutions that comply with the recommendations is often required (Fig. 1 ). Such manipulations give rise to significant patient risks regarding the uncertainty in physico-chemical stability, microbial contamination, prescription and preparation errors while manipulating electrolytes, as well as alterations of the tonicity and/or the balanced nature of the original fluid ( 6 ). Some clinicians have considered using paediatric IV fluids marketed for the peri-operative period as alternatives that are balanced isotonic fluids with 1% glucose. ISOPEDIA© (FRESENIUS KABI FRANCE) or BENELYTE© (FRESENIUS KABI POLSKA) are the only balanced isotonic glucose containing crystalloids available in many European countries. Their marketing authorisation was obtained in 2017, based on perioperative IV-MFT guidelines in children, which recommended a 1 to 2.5% glucose concentration ( 7 ). However, this glucose containing fluid is probably not appropriate for use outside of the perioperative setting, as they provide insufficient amount of glucose. No clear consensus exists on the optimal glucose concentration for paediatric IV-MFT. In the general paediatric setting, 5% glucose concentration solutions are common and recommended by some medical societies ( 8 ) probably based on Holliday and Segar guidance ( 5 ). Likewise, adult guidelines suggest considering a daily glucose intake of 1 to 1.5 g/kg/day to prevent fasting ketonemia ( 9 ). We consider that isotonic balanced solutions which would provide different ranges of glucose (from 1 to 10%) should be favoured and made readily available on the market to ensure safe IV fluid therapy for children. In addition, as the insufficient amount of potassium in some balanced fluids has been called into question and may contribute to impairing the applicability of the guidelines, those fluids should be available with a sufficient amount of potassium for use in standard paediatric IV maintenance therapy ( 10 ). Specific considerations should be made regarding potassium content when bolus fluids are used or in case of renal failure. Finally, consideration should be given to cost and packaging. If these recommendations are to be applicable worldwide, including in low- and middle-income countries, the recommended fluids must be available at a reasonable price ( 11 ). In addition, to overcoming the wide variability in patient characteristics encountered in paediatric practice, the recommended fluids should be available in a range of packaging formats, in order to reduce waste as well as the environmental footprint of plastic packaging ( 12 ). The limitations inherent to the original survey were presented in ( 1 ). This study’s specific limitations mainly lie within the fact that the survey was not originally dedicated to determining the different fluids availability. It is therefore difficult to confirm that unavailability of the appropriate fluid in responding centres of one country reflects the absence of marketing of the fluid within the country or the simple lack of product referencing in the responding centre (due to cost issues or poor regard to the necessity of the product). Conclusion Ready-to-use isotonic balanced IV solutions containing glucose in sufficient amounts exist but are inconsistently available through Europe. National and European Medication Safety Incentives should guarantee availability of the most appropriate and safest IV-MFT solution for all children. Abbreviations AAP - American Academy of Pediatrics ESPNIC - European Society of Pediatric and Neonatal Intensive Care IV - Intravenous IV-MFT - Intravenous maintenance fluid therapy PICU - Paediatric intensive care unit Declarations Acknowledgements: We acknowledge with gratitude those respected colleagues who were involved in the distribution of the survey within their country and region: Sanja Simic and Dejan Milojevic (Serbia), Jeppe Sylvest Angaard Nielsen (Danemark), Mari-Liis Ilmoja (Estonia), Josko Markic (Croatia), Rachel Elizabeth Grech (Malta), Reinis Balmaks (Latvia). Authors’ Contributions: DWB, LNT and FVV assumed supervision of the core team. DWB, IG, CM, LNT and FVV, developed the study protocol; CM, FA, HM, DWB, LNT and FVV developed and piloted the survey tool. DWB, IG, LNT and FVV conceptualized the article. DWB, IG, and FP drafted the first version of the manuscript. DWB, IG, and FP contributed to the design of the table. IG and LNT edited the manuscript in English. All authors reviewed, edited, and approved the manuscript. Availability of data and material: All data that support the findings of this study will be available from the corresponding author upon reasonable request. Raw data were submitted as supplemental material with the publication of Morice et al. Ethics approval: Our protocol was analysed within the Research Ethics Committee (CLERS) and was approved on May 2021. Due to the nature of the study, the Institutional Review Board waived the need for informed consent. Informed consent: not applicable Ethical clearance: not applicable Funding: No funding was received for the conduct of the review Competing interest: DWB and IG received honoraria for presentations from BBraun. LNT received honoraria for presentations from Nestle. FVV received honoraria for presentations from Baxter, Nutricia and Nestle Health Care. For the remaining authors, none was declared. References Morice C, Alsohime F, Mayberry H, Tume LN, Brossier D, Valla FV, et al. Intravenous maintenance fluid therapy practice in the pediatric acute and critical care settings: a European and Middle Eastern survey. Eur J Pediatr. 2022;181(8):3163‑72. Feld LG, Neuspiel DR, Foster BA, Leu MG, Garber MD, Austin K, et al. Clinical Practice Guideline: Maintenance Intravenous Fluids in Children. Pediatrics. 2018;142(6):e20183083. Brossier DW, Tume LN, Briant AR, Jotterand Chaparro C, Moullet C, Rooze S, et al. ESPNIC clinical practice guidelines: intravenous maintenance fluid therapy in acute and critically ill children— a systematic review and meta-analysis. Intensive Care Med. 2022;48(12):1691‑708. Stenson EK, Cvijanovich NZ, Anas N, Allen GL, Thomas NJ, Bigham MT, et al. Hyperchloremia Is Associated With Complicated Course and Mortality in Pediatric Patients With Septic Shock*. Pediatr Crit Care Med. 2018;19(2):155‑60. Holliday MA, Segar WE. The maintenance need for water in parenteral fluid therapy. Pediatrics. 1957;19(5):823‑32. Denis M, Di Giacomo A, Lacotte E, Porcheret F, Letouzé N, Lauzier B, et al. From hypotonic maintenance fluid to severe hyponatremia: a case report. J Med Case Reports. 2021;15(1):315. Sümpelmann R, Becke K, Brenner S, Breschan C, Eich C, Höhne C, et al. Perioperative intravenous fluid therapy in children: guidelines from the Association of the Scientific Medical Societies in Germany. Pediatr Anesth. 2017;27(1):10‑8. Surveillance of intravenous fluid therapy in children and young people in hospital (NICE guideline NG29). 2020;11. Malbrain MLNG, Langer T, Annane D, Gattinoni L, Elbers P, Hahn RG, et al. Intravenous fluid therapy in the perioperative and critical care setting: Executive summary of the International Fluid Academy (IFA). Ann Intensive Care.2020;10(1):64. Lehtiranta S, Honkila M, Kallio M, Paalanne N, Peltoniemi O, Pokka T, et al. Risk of Electrolyte Disorders in Acutely Ill Children Receiving Commercially Available Plasmalike Isotonic Fluids: A Randomized Clinical Trial. JAMA Pediatr. 2021;175(1):28. Kovacevic P, Meyer FJ, Gajic O. Challenges, obstacles, and unknowns in implementing principles of modern intensive care medicine in low-resource settings: an insider’s perspective. Intensive Care Med 2023. doi.org/10.1007/s00134-023-07270-x McGain F, McAlister S. Reusable versus single-use ICU equipment: what’s the environmental footprint? Intensive Care Med. 2023;49(12):1523‑5. Additional Declarations Competing interest reported. DWB and IG received honoraria for presentations from BBraun. LNT received honoraria for presentations from Nestle. FVV received honoraria for presentations from Baxter, Nutricia and Nestle Health Care. For the remaining authors, none was declared. Supplementary Files ResultatsEJPHtoFtheGuidelinesSDC1.docx Supplemental digital content 1: Impact of the country on prescription practices ResultatsEJPHtoFtheGuidelinesSDC2.docx Supplemental digital content 2: Impact of the availability of balanced fluid on prescription practices Cite Share Download PDF Status: Published Journal Publication published 18 Mar, 2024 Read the published version in European Journal of Pediatrics → Version 1 posted Editorial decision: Revision requested 11 Feb, 2024 Reviews received at journal 09 Feb, 2024 Reviewers agreed at journal 05 Feb, 2024 Reviewers invited by journal 05 Feb, 2024 Editor assigned by journal 04 Feb, 2024 Submission checks completed at journal 04 Feb, 2024 First submitted to journal 23 Jan, 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. 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DWB and IG received honoraria for presentations from BBraun. LNT received honoraria for presentations from Nestle. FVV received honoraria for presentations from Baxter, Nutricia and Nestle Health Care. For the remaining authors, none was declared.","formattedTitle":"How to follow the guidelines, when the appropriate fluid is missing?","fulltext":[{"header":"What is Known","content":"\u003cp\u003e\u0026bull; Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care.\u003c/p\u003e\n\u003cp\u003e\u0026bull; Balanced isotonic fluid is recommended when prescribing IV-MFT in both acute and critical paediatric care.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eWhat is New:\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; Balanced isotonic fluid with glucose 5% is available for less than 25% of the prescribers in Europe and Middle East.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026bull; Availability of balanced isotonic fluid with glucose 5% varies from one country to another but can also be inconsistent within the same country.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026bull; Clinicians who have access to a ready-to-use balanced isotonic fluid with glucose 5% are more likely to consider its use than clinicians who do not have access to such an IV solution.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eIntravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It has been used for more than a century and yet, it\u0026rsquo;s only recently that paediatric societies have produced evidence-based practice guidelines to guide the use of IV fluids in clinical practice (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). These guidelines recommend the use of balanced isotonic fluid when prescribing IV-MFT in both acute and critical paediatric care. It is also recommended to provide the appropriate amounts of potassium and glucose to prevent children from presenting hypokalaemia and hypoglycaemia (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). However, even though two international paediatric societies (the American Academic of Pediatrics (AAP) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) and the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)) are to be commended for these long-awaited guidelines, the applicability and implementation of these guidelines is threatened by a lack of these fluids available. During the last decade, the growing interest in the use of balanced crystalloids to prevent patients from developing clinical complications and mortality related to hyperchloremia and metabolic acidosis, has been associated with a growing availability of balanced IV fluids (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Unfortunately, amongst this variety of available balanced IV fluids, very few, or even none in certain countries, contain glucose. However, glucose content is fundamental for paediatric IV-MFT. In 2022, Morice et al. showed that the absence of glucose in the solution was the main reason for not prescribing a balanced fluid by 29.4% of the respondents (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The main objective of this study was to describe the availability of glucose containing balanced isotonic fluids in European and Middle Eastern paediatric acute and critical care settings, performing a complementary analysis of Morice et al. 2022 survey. The secondary objective was to evaluate the impact of the absence of paediatric appropriate ready-to-use fluids on IV-MFT declarative practice.\u003c/p\u003e"},{"header":"Materials and method","content":"\u003cp\u003eThis work was an ancillary study of the survey dedicated to IV-MFT practice in the paediatric acute and critical care settings in 34 countries in Europe and Middle East (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The study design, the included population and the survey instrument development, content and data collection have previously been published (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eData were analysed according to the country of the responders and according to the availability of balanced isotonic fluids, with or without glucose 5%. The data analysis was focused on the questions related to the use of balanced fluids (Q13,14,15,16) and fluid choices (Q17,18,19,20).\u003c/p\u003e \u003cp\u003eWe used a summative score to summarize the results from Likert scale questions for each participant. Variables distributions were assessed by the Shapiro\u0026ndash;Wilk comparison test and continuous variables were presented as median [min-max]. Categorical variables were presented as number (percentage). Comparisons between both groups were made by a Mann\u0026ndash;Whitney U test or a Kruskal-Wallis\u0026rsquo;s test for continuous variables as appropriate and by a Chi-square test with Monte Carlo simulation with 2000 replicates for categorical variables. The level of statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Statistical analyses were performed using open-access R software (Version 4.2.1; R Foundation for Statistical Computing, Vienna, Austria). Ethical approval was obtained from Caen-France institutional review board (reference number 2474).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u0026rsquo; characteristics\u003c/h2\u003e \u003cp\u003eParticipants\u0026rsquo; characteristics were presented in (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The response rate of this survey was considered above 60%, with 153 centres represented. One participant was excluded for practicing in Australia.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eFluid availability according to country\u003c/h2\u003e \u003cp\u003eFluid availability according to the country of the responders is presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Balanced Isotonic Fluid with glucose 5% was declared available for only 32 (21%) responders. Balanced Isotonic Fluid with glucose 5% was consistently available only in the United Kingdom (90%) and totally absent from France, Greece, The Netherlands and Turkey. The most widely available fluids were balanced (93.5%) and unbalanced (87.6%) isotonic fluids without glucose.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFluid availability in Europe and Middle East\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"16\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBelgium\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFrance\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGermany\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGreece\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePoland\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePortugal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSpain\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eSwitzerland\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eThe Netherlands\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eTurkey\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003eUnited Kingdom\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c15\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;153\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;7\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;17\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;9\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;7\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;19\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;11\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;9\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c15\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;34\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBalanced Isotonic Fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e143\u003c/p\u003e \u003cp\u003e(93.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(85.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003cp\u003e(88.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e(80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e17\u003c/p\u003e \u003cp\u003e(89.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e(88.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e32\u003c/p\u003e \u003cp\u003e(94.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBalanced Isotonic Fluid with glucose 5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (21.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(57.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(11.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(42.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(27.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e(90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e(14.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBalanced Isotonic Fluid with glucose 1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (15.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e(47.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(30%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(36.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBalanced Hypotonic Fluid with glucose 5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnbalanced Isotonic Fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e134\u003c/p\u003e \u003cp\u003e(87.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(85.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003cp\u003e(82.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e(55.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e17\u003c/p\u003e \u003cp\u003e(89.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e(90.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e31\u003c/p\u003e \u003cp\u003e(91.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnbalanced Isotonic Fluid with glucose 5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(4.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnbalanced Hypotonic Fluid with glucose 5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114\u003c/p\u003e \u003cp\u003e(74.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(85.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e14\u003c/p\u003e \u003cp\u003e(73.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(63.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e(90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e24\u003c/p\u003e \u003cp\u003e(70.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003e- Balanced Isotonic Fluid are: Ringer\u0026rsquo;s lactate, Ringer\u0026rsquo;s acetate, Hartamann\u0026rsquo;s solution, Plasmalyte, Isolyte E \u0026amp; S, Normosol R, Isofundine, Sterofundine, Ringerfundine, Optilyte\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003e- Balanced Isotonic Fluid with glucose 5% are: PlasmalyteG5, Sterofundine VG5\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003e- Balanced Isotonic Fluid with glucose 1% are: Isopedia, Benelyte\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003e- Balanced Hypotonic Fluid with glucose 5% are: Normosol M, Sterofundine HEG 5, Isolyte G,M \u0026amp; P.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003e- Unbalanced Isotonic Fluid is: NaCl 0.9%\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003e- Unbalanced Isotonic Fluid with glucose 5% is: G5NaCl0.9%\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003e- Unbalanced Hypotonic Fluid with glucose 5% are: Glucidion, Osmotan, Bionolyte, Polyionique, Dextrion.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003eImpact of country on prescription practices\u003c/h2\u003e \u003cp\u003eResponders\u0026rsquo; consideration for the importance of balanced fluids varies considerably between countries in both conventional and critical care unit (SDC 1). Prescription practices varied considerably between countries (SDC 1). Balanced isotonic fluid was considered in 45.0% of the clinical situations (from 6.5% in Greece to 83.3% in Poland) and unbalanced isotonic fluid in 42.8% (from 11.1% in Poland to 78.5% in Turkey). Hypotonic unbalanced fluid was considered in 10.5% of the clinical situations (from 0% in the UK to 30% in Greece). It was consistently the less prescribed fluid, except in France and in Greece, where it was prescribed more than balanced isotonic fluid.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003eImpact of fluid availability on prescriptions\u0026rsquo; practices\u003c/h2\u003e \u003cp\u003eAmong the 32 responders who declared having access to a balanced isotonic fluid with glucose 5%, 23 (71.9%) reported that balanced isotonic fluid should be always considered vs 42/121 (34.7%) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in the case of unavailability of a balanced isotonic fluid with glucose 5% (SDC 2). The availability of a balanced isotonic fluid with glucose 5% was systematically and significantly associated with a preference for prescribing this fluid over unbalanced isotonic or hypotonic crystalloids, notwithstanding the clinical situation studied (SDC 2).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePerforming a complementary analysis on the declarative data of Morice et al. 2022 survey (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e), focusing on the declared type of available IV fluids, we have realized that only 21% of responders have access to a commercialized balanced isotonic fluid containing 5% glucose, which is considered as the current recommended IV fluid for paediatric IV-MFT. We have shown that the availability of such a solution varies from one country to another but can also be inconsistent within the same country. In addition, we have observed that the availability of a balanced isotonic fluid with 5% glucose was associated with a higher declarative use of balanced isotonic fluid in almost all the assessed clinical situations. This inconsistency regarding the availability of these ready-made balanced solutions are a significant barrier to the implementation of the recent ESPNIC IV-MFT guidelines into clinical practices and could explain the obsolete but still current use of hypotonic IV fluids (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). This should be reassessed once a specific model for disseminating these guidelines in clinical practice has been implemented.\u003c/p\u003e \u003cp\u003eIn the absence of a ready-to-use appropriate IV fluid for children, local compounding to make solutions that comply with the recommendations is often required (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Such manipulations give rise to significant patient risks regarding the uncertainty in physico-chemical stability, microbial contamination, prescription and preparation errors while manipulating electrolytes, as well as alterations of the tonicity and/or the balanced nature of the original fluid (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Some clinicians have considered using paediatric IV fluids marketed for the peri-operative period as alternatives that are balanced isotonic fluids with 1% glucose. ISOPEDIA\u0026copy; (FRESENIUS KABI FRANCE) or BENELYTE\u0026copy; (FRESENIUS KABI POLSKA) are the only balanced isotonic glucose containing crystalloids available in many European countries. Their marketing authorisation was obtained in 2017, based on perioperative IV-MFT guidelines in children, which recommended a 1 to 2.5% glucose concentration (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). However, this glucose containing fluid is probably not appropriate for use outside of the perioperative setting, as they provide insufficient amount of glucose. No clear consensus exists on the optimal glucose concentration for paediatric IV-MFT. In the general paediatric setting, 5% glucose concentration solutions are common and recommended by some medical societies (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) probably based on Holliday and Segar guidance (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Likewise, adult guidelines suggest considering a daily glucose intake of 1 to 1.5 g/kg/day to prevent fasting ketonemia (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). We consider that isotonic balanced solutions which would provide different ranges of glucose (from 1 to 10%) should be favoured and made readily available on the market to ensure safe IV fluid therapy for children. In addition, as the insufficient amount of potassium in some balanced fluids has been called into question and may contribute to impairing the applicability of the guidelines, those fluids should be available with a sufficient amount of potassium for use in standard paediatric IV maintenance therapy (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Specific considerations should be made regarding potassium content when bolus fluids are used or in case of renal failure. Finally, consideration should be given to cost and packaging. If these recommendations are to be applicable worldwide, including in low- and middle-income countries, the recommended fluids must be available at a reasonable price (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In addition, to overcoming the wide variability in patient characteristics encountered in paediatric practice, the recommended fluids should be available in a range of packaging formats, in order to reduce waste as well as the environmental footprint of plastic packaging (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe limitations inherent to the original survey were presented in (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). This study\u0026rsquo;s specific limitations mainly lie within the fact that the survey was not originally dedicated to determining the different fluids availability. It is therefore difficult to confirm that unavailability of the appropriate fluid in responding centres of one country reflects the absence of marketing of the fluid within the country or the simple lack of product referencing in the responding centre (due to cost issues or poor regard to the necessity of the product).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eReady-to-use isotonic balanced IV solutions containing glucose in sufficient amounts exist but are inconsistently available through Europe. National and European Medication Safety Incentives should guarantee availability of the most appropriate and safest IV-MFT solution for all children.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAAP - American Academy of Pediatrics\u003c/p\u003e\n\u003cp\u003eESPNIC - European Society of Pediatric and Neonatal Intensive Care\u003c/p\u003e\n\u003cp\u003eIV - Intravenous\u003c/p\u003e\n\u003cp\u003eIV-MFT - Intravenous maintenance fluid therapy\u003c/p\u003e\n\u003cp\u003ePICU - Paediatric intensive care unit\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eAcknowledgements:\u003c/em\u003e We acknowledge with gratitude those respected colleagues who were involved in the distribution of the survey within their country and region: Sanja Simic and Dejan Milojevic (Serbia), Jeppe Sylvest Angaard Nielsen (Danemark), Mari-Liis Ilmoja (Estonia), Josko Markic (Croatia), Rachel Elizabeth Grech (Malta), Reinis Balmaks (Latvia).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors\u0026rsquo; Contributions:\u0026nbsp;\u003c/em\u003eDWB, LNT and FVV assumed supervision of the core team. DWB, IG, CM, LNT and FVV, developed the study protocol; CM, FA, HM, DWB, LNT and FVV developed and piloted the survey tool. DWB, IG, LNT and FVV conceptualized the article. DWB, IG, and FP drafted the first version of the manuscript. DWB, IG, and FP contributed to the design of the table. IG and LNT edited the manuscript in English. All authors reviewed, edited, and approved the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and material:\u003c/em\u003e All data that support the findings of this study will be available from the corresponding author upon reasonable request. Raw data were submitted as supplemental material with the publication of Morice et al.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthics approval:\u003c/em\u003e Our protocol was analysed within the Research Ethics Committee (CLERS) and was approved on May 2021. Due to the nature of the study, the Institutional Review Board waived the need for informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eInformed consent:\u003c/em\u003e not applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthical clearance:\u003c/em\u003e not applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding:\u003c/em\u003e No funding was received for the conduct of the review\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interest:\u0026nbsp;\u003c/em\u003eDWB and IG received honoraria for presentations from BBraun. LNT received honoraria for presentations from Nestle. FVV received honoraria for presentations from Baxter, Nutricia and Nestle Health Care. For the remaining authors, none was declared.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMorice C, Alsohime F, Mayberry H, Tume LN, Brossier D, Valla FV, et al. Intravenous maintenance fluid therapy practice in the pediatric acute and critical care settings: a European and Middle Eastern survey. Eur J Pediatr. 2022;181(8):3163‑72. \u003c/li\u003e\n\u003cli\u003eFeld LG, Neuspiel DR, Foster BA, Leu MG, Garber MD, Austin K, et al. Clinical Practice Guideline: Maintenance Intravenous Fluids in Children. Pediatrics. 2018;142(6):e20183083. \u003c/li\u003e\n\u003cli\u003eBrossier DW, Tume LN, Briant AR, Jotterand Chaparro C, Moullet C, Rooze S, et al. ESPNIC clinical practice guidelines: intravenous maintenance fluid therapy in acute and critically ill children\u0026mdash; a systematic review and meta-analysis. Intensive Care Med. 2022;48(12):1691‑708. \u003c/li\u003e\n\u003cli\u003eStenson EK, Cvijanovich NZ, Anas N, Allen GL, Thomas NJ, Bigham MT, et al. Hyperchloremia Is Associated With Complicated Course and Mortality in Pediatric Patients With Septic Shock*. Pediatr Crit Care Med. 2018;19(2):155‑60. \u003c/li\u003e\n\u003cli\u003eHolliday MA, Segar WE. The maintenance need for water in parenteral fluid therapy. Pediatrics. 1957;19(5):823‑32. \u003c/li\u003e\n\u003cli\u003eDenis M, Di Giacomo A, Lacotte E, Porcheret F, Letouz\u0026eacute; N, Lauzier B, et al. From hypotonic maintenance fluid to severe hyponatremia: a case report. J Med Case Reports. 2021;15(1):315. \u003c/li\u003e\n\u003cli\u003eS\u0026uuml;mpelmann R, Becke K, Brenner S, Breschan C, Eich C, H\u0026ouml;hne C, et al. Perioperative intravenous fluid therapy in children: guidelines from the Association of the Scientific Medical Societies in Germany. Pediatr Anesth. 2017;27(1):10‑8. \u003c/li\u003e\n\u003cli\u003eSurveillance of intravenous fluid therapy in children and young people in hospital (NICE guideline NG29). 2020;11. \u003c/li\u003e\n\u003cli\u003eMalbrain MLNG, Langer T, Annane D, Gattinoni L, Elbers P, Hahn RG, et al. Intravenous fluid therapy in the perioperative and critical care setting: Executive summary of the International Fluid Academy (IFA). Ann Intensive Care.2020;10(1):64. \u003c/li\u003e\n\u003cli\u003eLehtiranta S, Honkila M, Kallio M, Paalanne N, Peltoniemi O, Pokka T, et al. Risk of Electrolyte Disorders in Acutely Ill Children Receiving Commercially Available Plasmalike Isotonic Fluids: A Randomized Clinical Trial. JAMA Pediatr. 2021;175(1):28. \u003c/li\u003e\n\u003cli\u003eKovacevic P, Meyer FJ, Gajic O. Challenges, obstacles, and unknowns in implementing principles of modern intensive care medicine in low-resource settings: an insider\u0026rsquo;s perspective. Intensive Care Med 2023. doi.org/10.1007/s00134-023-07270-x\u003c/li\u003e\n\u003cli\u003eMcGain F, McAlister S. Reusable versus single-use ICU equipment: what\u0026rsquo;s the environmental footprint? Intensive Care Med. 2023;49(12):1523‑5. \u003c/li\u003e\n\u003c/ol\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":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Intravenous fluids, Balanced fluids, Isotonic Fluids","lastPublishedDoi":"10.21203/rs.3.rs-3892154/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3892154/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. Recently paediatric societies have produced evidence-based practice guidelines that recommend the use of balanced isotonic fluid when prescribing IV-MFT in both acute and critical paediatric care. Unfortunately, the applicability of these guidelines could be called into question when a ready-to-use glucose containing balanced isotonic fluid is not available. The main objective of this study was to describe the availability of glucose containing balanced isotonic fluids in European and Middle Eastern paediatric acute and critical care settings. This work is an ancillary study of the survey dedicated to IV-MFT practices in the paediatric acute and critical care settings in Europe and Middle East, a cross-sectional electronic 27-item survey, emailed in April\u0026ndash;May 2021 to paediatric critical care physicians across 34 European and Middle East countries. The survey was developed by an expert multi-professional panel within the European Society of Peadiatric and Neonatal Intensive Care (ESPNIC). Balanced Isotonic Fluid with glucose 5% was available for only 32/153 (21%) responders. Balanced Isotonic Fluid with glucose 5% was consistently available in the United Kingdom (90%) but not available in France, Greece, The Netherlands and Turkey. Ready-to-use isotonic balanced IV solutions containing glucose in sufficient amount exist, but are inconsistently available through Europe. National and European Medication Safety Incentives should guarantee availability of the most appropriate and safest IV-MFT solution for all children.\u003c/p\u003e","manuscriptTitle":"How to follow the guidelines, when the appropriate fluid is missing?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-06 17:15:57","doi":"10.21203/rs.3.rs-3892154/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-02-11T06:15:36+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-02-09T10:03:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"96a044b9-a649-477c-9f97-84d02d1ea4cb","date":"2024-02-05T16:16:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-02-05T13:23:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-02-05T00:50:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-05T00:50:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Pediatrics","date":"2024-01-23T21:47:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"042818e1-2680-47da-b53f-73f7707c6a31","owner":[],"postedDate":"February 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-03-25T15:05:41+00:00","versionOfRecord":{"articleIdentity":"rs-3892154","link":"https://doi.org/10.1007/s00431-024-05514-6","journal":{"identity":"european-journal-of-pediatrics","isVorOnly":false,"title":"European Journal of Pediatrics"},"publishedOn":"2024-03-18 15:01:07","publishedOnDateReadable":"March 18th, 2024"},"versionCreatedAt":"2024-02-06 17:15:57","video":"","vorDoi":"10.1007/s00431-024-05514-6","vorDoiUrl":"https://doi.org/10.1007/s00431-024-05514-6","workflowStages":[]},"version":"v1","identity":"rs-3892154","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3892154","identity":"rs-3892154","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}