Clinical and echocardiographic response to volume expansion in hypotensive preterm infants

Clinical and echocardiographic response to volume expansion in hypotensive preterm infants | 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 Article Clinical and echocardiographic response to volume expansion in hypotensive preterm infants Océane Lalin, Jean-Marc Jelliman, Jean-Michel HASCOET This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7100478/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective : Hemodynamic instability is common in preterm neonates. Volume expansion remains controversial due to its uncertain efficacy and potential adverse effects. The objective was to evaluate the effects of volume expansion in preterm infants with hypotension within 24 hours of birth. Study Design : Retrospective study of preterm neonates receiving modified fluid gelatin for hypotension. Clinical and echocardiographic parameters were compared before and after treatment. Results : In 31 infants, volume expansion significantly increased systolic, diastolic, and mean arterial pressures (mean increase: +6, +3, +4 mmHg respectively; p < 0.0001), and decreased heart rate (−10 bpm) and capillary refill time (−0.5 s; p < 0.0001). Improved echocardiographic markers of preload and output included Left Ventricular End-Diastolic Diameter (+1.3 mm), Superior Vena Cava flow (+16.2 ml/kg/min), and ductus arteriosus shunt velocity (+0.21 m/s). No adverse effects were reported. Conclusion : Volume expansion improved clinical and echocardiographic parameters in hypotensive preterm infants without observed complications. Health sciences/Medical research/Outcomes research Health sciences/Health care/Paediatrics preterm hemodynamic impairment volume expansion Ultrasound Figures Figure 1 1. Introduction Hemodynamic disturbances are common in preterm infants during the first hours of life. In clinical practice, this impairment in circulatory adaptation is usually identified by a drop in blood pressure, which tends to decrease in the first hours after birth.( 1 , 2 ) However, blood pressure measurement is only an approximate indicator of tissue perfusion, which also depends on cardiac output and heart rate. When these parameters are disturbed, there is a risk of cellular damage by tissue ischemia, followed by ischemia-reperfusion phenomena, particularly at the brain level ( 3 ) Simple clinical parameters used to detect tissue hypoperfusion include blood pressure, urine output, capillary refill time and heart rate. In addition, cardiac ultrasound is a simple, non-invasive method of hemodynamic assessment. It provides a pathophysiological perspective on hemodynamic disturbances and helps guide therapeutic choices. Neonatologists can easily analyze parameters such as shunts through the foramen ovale and ductus arteriosus, ventricular preload, ventricular function and possible pulmonary hypertension ( 4 , 5 ). Superior vena cava (SVC) flow is another useful parameter, reflecting cerebral perfusion. It has been shown that when SVC flow is below 40 ml/kg/min, there is a clear risk of cerebral hypoperfusion and intraventricular hemorrhage in very premature infants. ( 6 – 8 ) Treatment of these circulatory adaptation disorders is not standardized. In practice, optimization of ventricular preload by vascular filling is usually proposed as soon as arterial hypotension is present. However, this treatment has not been proven effective on tissue perfusion, and can be deleterious. It is relevant in case of hypovolemia, but this situation is not constant, and sometimes a vasopressor or inotropic treatment will be introduced as a first-line therapy. ( 9 – 12 ) Filling products are numerous and classified as colloids or crystalloids. There is no official recommendation on the use of one filling solution or another( 13 ). Crystalloids include balanced solutions, ringer lactate and 0.9% NaCl. Colloids include blood-derived products such as concentrated red blood cells, albumin or modified fluid gelatin. Modified fluid gelatin 4 contains 150ml/L sodium and an osmolarity of 295 mOsm/Kg and may be used as an alternative to crystalloids in case of hypovolemic or vasoplegic shock. ( 14 ) Decisions regarding volume expansion should integrate clinical, biological, and ultrasound criteria. Unwarranted volume expansion can lead to complications such as pulmonary hemorrhage, increased pulmonary shunt through PDA and foramen ovale, or excessive preload leading to pulmonary edema, Moreover, volume overload can contribute to cerebral hemorrhage due to elevated venous pressure, systolic and/or diastolic dysfunction, or impaired cerebral autoregulation.( 15 , 16 ) The aim of this study is to identify what are the clinical and ultrasound impacts of volume expansion in the hypotensive preterm neonate in the first 24 hours of life. The clinical and echocardiographic impact, as well as short- and long-term complications, will be analyzed. 2. Material and Method 2.1.Type of Study: This was a monocentric retrospective observational study carried out in the neonatal intensive care unit at the Nancy regional maternity hospital. 2.2.Study population : Inclusion criteria were preterm infants between 26- and 31-weeks + 6 days of gestation admitted over a 7 months period in the neonatal intensive care Unit at the Nancy Regional Maternity Hospital. The infants were intubated-ventilated presenting arterial hypotension during the first 24 hours of life (defined as mean arterial pressure (MAP) value below gestational age in completed weeks), and who received macromolecular volume expansion by modified fluid gelatin following echocardiography evaluation. Exclusion criteria were malformative heart disease other than persistent fetal shunts or small ventricular septal defect (VSD) of less than 2 mm diameter. Infants with diagnosed chromosomal abnormalities. Infant who had received prior hemodynamic treatment (vascular filling or vasopressor amines) were also excluded. 2.3.Data collection The list of infants born very prematurely during the study period was obtained from the Medical Information Department of Nancy University Hospital. A table of correspondence (infant's name, date of birth, and anonymity number) was established and kept secure in an appropriate place (Office of the Head of Department). Only the infant's anonymity numbers appeared on the computer files created for the study (i.e., data collection, processing, and production of results). Data were collected from the hospitalization records, both computerized and paper files. We collected data on the first 24 hours of life, including vital signs: 3 blood pressure measurements with a cuff at 5 minutes, heart rate noted at each blood pressure measurement, infant's temperature, skin recoloration time. Ultrasound data from an ALOKA® ultrasound scanner, with a 7 MHz phased-array probe, included : heart morphology, foramen ovale (size, direction of shunt and velocity, in subcostal section), ductus arteriosus (size, direction of shunt, velocity, in supra-sternal section), left ventricular ejection fraction in left parasternal short axis, left ventricular end-diastolic diameter in the same section, the diameter of the (Inferior Vena Cava) IVC and the IVC respiratory variation index ((max diameter - min diameter) / (max diameter + min diameter) / 2) at the junction with the right atrium in longitudinal section of the IVC, SVC flow measurement (mean velocity over 8 cardiac cycles in subcostal section and mean measurement between maximum and minimum SVC diameter in high parasternal long-axis incidence, using the formula SVC flow (in ml/kg/min) = mean velocity in cm/s x π x (mean SVC radius in cm)2/weight in kg. Pulmonary pressures were assessed by measuring tricuspid insufficiency when present, and flow in the ductus arteriosus when open. These data were collected before and after volume expansion with Modified fluid gelatin at a dose of 20 ml/kg over 1 hour, according to the department's protocol at the time of inclusion. Data concerning the short- and medium-term evolution of the infant included hemodynamic management beyond vascular filling, and possible management of the ductus arteriosus (medical or surgical management), respiratory evolution with date of extubation and occurrence of bronchopulmonary dysplasia, occurrence of retinopathy and lesions on transfontanellar ultrasound, occurrence of ulcerative colitis and survival. Our Institutional Review Board approved the study (Delegation à la Recherche Clinique et à l'Innovation du CHRU de Nancy ; DRCI number: n°2024PI174-531) Parents provided written consent for their infant's data to be used for research purposes. 2.4.Statistical analysis Categorical data are presented as numbers or percentages. Chi-squared was used to evaluate the differences between groups for categorical variables. Continuous variables that were not normally distributed are presented as medians with the interquartile range (IQR) and were analyzed using the Mann-Whitney U test. A p-value < 0.05 was considered significant. All analyses were performed in SAS/STAT (Statistical Analysis System 9.4; 6th Edition). 3. Results Thirty-one infants were analyzed (Fig. 1 ). The median gestational age of these infants was 29 weeks (28;30) of amenorrhea, with a median weight of 1238(1218;1254). The median time from birth was 3 hours (2;5). The characteristics of the population are presented Table 1 . Table 1 Characteristics of the population Median(Q1 ; Q3) N (%) Gestational age (week of amenorrhea) 29 (28 ; 30) Weight (g) 1238 (1218 ; 1254) Apgar 1 min 5 (3 ; 6.5) Apgar 5 min 7 (6 ; 8) pH at the umbilical cord 7.295 (7.26 ; 7.33) Lactic acid at the umbilical cord 2.9 (2.3 ; 4.7) IUGR 3 (10%) Premature rupture of membranes 12 (39%) cesarean section 20 (65%) General anesthesia 6 (20%) Peridural anesthesia 21 (70%) Hyaline membrane disease 19 (61%) IUGR = Intrauterine Growth Restriction Volume expansion had a significant influence, increasing systolic pressure by 6 mmHg (p < 0.0001), diastolic pressure by 3 mmHg (p < 0.0001), mean arterial pressure by 4 mmHg(p < 0.0001), significantly decreasing heart rate by 10 bpm (p < 0.0001) and capillary refill time (CRT) by 0.5 seconds (p < 0.0001) (Table 2 ). Table 2 Effect of volume expansion on clinical parameters Before (median (Q1 ; Q3)) After (median (Q1 ; Q3)) p SBP (mmHg) 37 (34.5 ; 40) 43 (39.5 ; 47) < 0.0001 DBP (mmHg) 17 (15 ; 19.5) 20 (16.5 ; 24.5) < 0.0001 MBP (mmHg) 24 (23 ; 26) 28 (24.5 ; 31) < 0.0001 HR (bpm) 155 (144 ; 171) 145 (136.5 ; 149) < 0.0001 CRT (s) 2.5 (2 ; 3) 2 (1.5 ; 2.2) 0.0019 SBP = systolic blood pressure, DBP = diastoli cblood pressure, MBP = Mean blood pressure, HR = Heart rate, CRT = Capillary refill time Regarding echocardiographic parameters, we observed a significantly faster mean velocity of the Left to right shunt in the PDA after volume expansion of 0.21 m/s (p = 0.004), a significantly greater left ventricular end-diastolic diameter of 1.3 mm (p < 0.01), a significantly greater mean velocity in the left pulmonary artery of 0.09 m/s (p = 0.01), a significantly greater superior vena cava diameter of 0.6 mm(p = 0.0001) and a significantly greater flow at the superior vena cava output of 16.2 ml/kg/min (p = 0.02) (Table 3 ). Table 3 Effect of volume expansion on echocardiographic parameters before N = 31 after N = 31 p PDA yes 30 (96%) 31 30 (100%) 30 diameter (mm) 1.8 (1.3 ; 2.45) 30 1.5 (1.15 ; 2.3) 30 0.13 shunt direction - LR - Bidirectionnal 11 (37%) 19 (63%) 30 12 (40%) 18 (60%) 30 1 shunt LR velocity (m/s) 0.86 (0.55 ; 1.26) 30 1.07 (0.8 ; 1.46) 30 0.004 shunt RL velocity (m/s) 0.34 (0-0.64) 19 0.39 (0 ; 0.78) 18 0.9 right-left time to cycle ratio 0.16 (0 ; 0,285) 19 0.17 (0 ; 0.3) 18 0.63 systemic pulmonary arterial pressure (mmhg) 34 (31 ; 38.75) 30 37 (34 ; 41.7) 30 0.05 TR systemic pulmonary arterial pressure (mmhg) 29 (23.5 ; 33) 19 33 (30 ; 36) 21 0.07 PFO yes 26 (84%) 31 28 (93%) 30 measure (mm) 2,3 (1.6 ; 2.9) 25 2.5 (1.5 ; 3.4) 28 0.33 LR shunt 5 (20%) 25 12 (43%) 28 Bidirectionnal shunt 20 (80%) 25 16 (57%) 28 shunt LR velocity (m/s) 0.36 (0.2 ; 0.55) 20 0.57 (0.48 ; 0.77) 12 0.81 shunt RL velocity (m/s) 0.16 (0 ; 0.225) 28 0.12 (0 ; 0.2) 24 0.02 LVEF (%) 75 (71.5 ; 80) 30 75.5 (70.7 ; 79.25) 29 0.8 left ventricular end-diastolic diameter (mm) 11.6 (11.05 ; 12.8) 30 12.9 (11.9 ; 13.6) 29 < 0.01 Mean velocity of left pulmonary artery (m/s) 0.35 (0.3 ; 0.42) 29 0.44 (0.37 ; 0.47) 28 0.01 Inferior vena cava variability index 0.25 (0.13–0.35) 30 0.20 (0.09 ; 0.4) 29 0.59 Superior vena cava Max. diameter (mm) 3.4 (2.8 ; 3.85) 28 4 (3.2 ; 4.45) 23 0.001 Mean velocity (m/s) 0.20 (0.15 ; 0,25) 26 0.20 (0.16 ; 0.26) 28 0.74 output (ml/kg/min) 82.8 (48.8 ; 104.1) 24 99 (66.3 ; 99) 23 0.02 PDA = Patent Ductus Arteriosus, LR = Left to Right, RL = Right to Left, TR = Tricuspide regurgitation, PFO = Patent Foramen Ovale, LVEF = Left Ventricular Ejection Fraction There was no significant difference between CRT, ultrasound parameters and CRT normalization. Following a first volume expansion, 15 infants (48%) required further volume expansion, they all also received vasopressor support with Dopamine and Dobutamine. None of them received hydrocortisone hemisuccinate. There was no significant difference between the medium- and long-term evolution and the normalization of CRT after filling: there were 11 infants with CRT > or equal to 3 seconds, in this group, none required oxygen at 28 days versus 12 in the CRT or equal to 3 seconds group and 2 in the or equal to 3 seconds group and 2 in the < 3 seconds group (p = 1). There was also no significant difference in the persistence of hypotension after filling and medium- and long-term evolution. The medium- and long-term complications of the patients analyzed are presented in Table 4 . Table 4 Complications by patients treated BPD 16 (53%) moderate BPD 12 (40%) Mid BPD 2 (6.5%) Severe BPD 2 (6.5%) PDA tretaed by ibuprophen 3 (10%) PDA treated by surgery 2 (6%) IVH 4 (13%) IVH I 3 (10%) IVH II 0 IVH III 1 (3%) IVH IV 0 Retinopathy 2 (7%) Ulceronecrotizing enterocolitis 3 (10%) Death 1 (3%) BPD = bronchopulmonary dysplasia, IVH = Intraventricular Haemorrhage NICU : Neonatal intensive care unit 4. Discussion Our study showed that volume expansion with 20 ml/kg of modified fluid gelatin in case of arterial hypotension in very preterm neonates significantly improved systolic, mean, and diastolic blood pressure, as well as heart rate and CRT normalization. Volume expansion significantly increase left ventricular end-diastolic diameter (LVEDD), superior vena cava (SVC) flow, and heart rate also increased significantly following volume administration. Heart rate significantly decreased post-expansion. Since cardiac output is the product of heart rate and stroke volume, tachycardia is often a compensatory response to hypovolemia-induced stroke volume reduction. However, isolated tachycardia should not automatically prompt volume expansion; other causes must be investigated if hemodynamic failure is absent. We observed a significant reduction in CRT following volume expansion. CRT serves as an objective marker of skin microcirculation, yet ultrasound findings did not show differences in volume expansion response between neonates with CRT ≥ 3s and those with CRT < 3s. Prior research suggests that CRT alone is an insufficient predictor of low systemic blood flow; its correlation with ascending aortic flow remains weak (r2 = 0.54) ( 17 ). Similarly, Osborn et al. demonstrated a poor positive predictive value for detecting low SVC flow ( 20 ). Instead, CRT should be used alongside other clinical, biological, and echocardiographic parameters. In 2008, Miletin et al. showed that combining SVC flow measurement with CRT > 4s has a positive predictive value of 100% for adverse outcomes such as hypoxic-ischemic encephalopathy (HIE) or death. ( 6 , 18 ) Our findings confirm a significant increase in LVEDD after volume expansion. LVEDD reflects ventricular preload, yet its measurement is highly dependent on optimal ultrasound technique. ( 19 ) SVC flow significantly increased post-expansion (p = 0.01), yet no correlation was found between SVC flow and blood pressure. Kluckow et al. (2004) identified SVC flow < 40 ml/kg/min as predictive of HIE or poor neurological outcomes at 3 years ( 5 ). However, SVC flow measurement is technically challenging and requires expertise in neonatal echocardiography. Inferior vena cava (IVC) size did not significantly change after volume expansion. While IVC measurement is widely used to estimate blood volume ( 20 ), our findings may be explained by the fact that most neonates in the study were under mechanical ventilation. High PEEP ventilation can increase IVC size while reducing its compliance, complicating its interpretation. Nevertheless, IVC assessment remains useful for neonates on spontaneous ventilation. This may be different nowadays, as premature infants are less likely to undergo invasive ventilation due to hydrocortisone hemisuccinate supplementation as per the PREMILOC protocol.( 21 ) Hemodynamic management in very preterm neonates is complex, blood pressure assessment should distinguish between systolic, diastolic, and mean arterial pressure. Postnatal adaptation involves increased pulmonary blood flow due to reduced pulmonary vascular resistance, leading to higher pulmonary venous return and increased preload, which elevates systolic blood pressure. However, if a patent ductus arteriosus (PDA) persists, a diastolic steal effect may occur, reducing diastolic and mean arterial pressure. ( 1 , 3 ) Hypovolemia can lead to low flow, which in turn is responsible for hemodynamic failure, with reduced mean arterial pressure and peripheral hypoperfusion.( 22 ) However, various clinical and biological parameters must be taken into account, not just mean arterial pressure to evaluate tissue perfusion in neonatology. ( 3 , 9 , 23 )We did not study diuresis, consciousness, respiratory mechanics and saturation, which are also important data to analyze when talking about hemodynamic failure.) ( 22 ) Compared with the literature( 24 ), there were no early or late complications in the group of premature infants who received modified fluid gelatin volume expansion within the first 24 hours of life. Volemic expansion could therefore be carried out without risk in the event of the ultrasound machine being unavailable in the presence of signs of peripheric hypoperfusion in the newborn. Our study presents limitations, first, it was a single-center observational study with a small sample size. Then, modified fluid gelatin, the colloid used, is no longer recommended in clinical practice. In addition, we did not collect biochemical markers or clinical variables such as urine output, consciousness level, respiratory mechanics, and oxygen saturation. While no adverse effects were noted, our study is not sufficient to definitively affirm the safety of volume expansion. However, the existing literature has not clearly demonstrated significant risks associated with this intervention. Another limitation is the absence of a control group, which limits our ability to compare the observed hemodynamic improvements to spontaneous postnatal adaptation. However, in the presence of hemodynamic failure, a control group would not be ethical. Modern neonatal care has evolved, with fewer preterm neonates requiring intubation due to improved volume status (delayed cord clamping or umbilical milking) and better vascular resistance management with hydrocortisone therapy. This evolving context should be considered when applying our findings to current practice. Despite these limitations, our study has notable strengths, Echocardiographic assessments were performed by experienced sonographers The same ultrasound equipment was used for all measurements, ensuring consistency. Data collection followed a standardized protocol. 5. Conclusion These findings justify not hesitating to perform volume expansion in preterm within the first 24 hours of life, when deemed necessary, particularly in sedated, intubated, and ventilated neonates, as in our cohort Volemic expansion has positive impact on mean arterial pressure, systolic arterial pressure, diastolic arterial pressure, LVEDD and superior vena cava flow, heart rate and CRT CRT measurements are not correlated with ultrasound measurements. If ultrasound is not available, it therefore seems reasonable to optimize blood volume before introducing other therapies in the event of hemodynamic failure. It would be interesting to carry out this study with the filling products currently in use, and to analyze their effectiveness in combination with the various factors mentioned above. Declarations Acknowledgements We thank Professor Rachel Vieux for the statistical analysis of the data Funding sources This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflicts of Interest The authors declare no conflicts of interes References Dasgupta SJ. Hypotension in the very low birthweight infant: the old, the new, and the uncertain. Arch Dis Child - Fetal Neonatal Ed. 1 nov 2003;88(6):450F ‑ 454. Lee J, Rajadurai VS, Tan KW. Blood pressure standards for very low birthweight infants during the first day of life. Arch Dis Child - Fetal Neonatal Ed. 1 nov 1999;81(3):F168‑70. Cayabyab R, McLean CW, Seri I. Definition of hypotension and assessment of hemodynamics in the preterm neonate. J Perinatol. mai 2009;29(S2):S58‑62. Lalin O, Gaga S, Hascoet JM. Management Practices for Hemodynamic Impairment in Neonates Born Prematurely: A Quality Improvement Project. J Clin Med. 14 nov 2024;13(22):6848. Kluckow M. 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Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. The Lancet. avr 2016;387(10030):1827‑36. Gupta S, Donn SM. Assessment of neonatal perfusion. Semin Fetal Neonatal Med. oct 2020;25(5):101144. Carrapato MRG, Andrade T, Caldeira T. Hypotension in small preterms: what does it mean? J Matern Fetal Neonatal Med. 2 déc 2019;32(23):4016‑21. Jensen EA, Schmidt B. Epidemiology of bronchopulmonary dysplasia. Birt Defects Res A Clin Mol Teratol. mars 2014;100(3):145‑57. Additional Declarations There is NO conflict of interest to disclose. Cite Share Download PDF Status: Posted Version 1 posted 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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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-7100478","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":486513937,"identity":"0a05ac4d-978d-45a1-ba6f-5719653858d1","order_by":0,"name":"Océane Lalin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIie3NIQvCQBjG8fdl4OKMJ4J+hRNBlvwsdwhbUgSLYPDGwZnEeuCXMBqVBcs+wIJBi3nRoOAGhoFy0yZy//jAjwfAZvvJHAEnCi0gpS0zExTAKHTLBHU1AeDiY+IBRhkbH8PVenkhuO2PPM1QTg2kIVASRi9DfTz0CCaDCUkZRomB0B2KnMTDDQlqzbty+IYw9yzMRF5zEtKcEFTzgmBUQVTxwp4kriYNicrPSUengeOjOnCdnCMj8VwZp9ktbns6wBTVjK8Wg72RgPOy1LkRvD3efStsNpvtz3sA6mVL2Vyco2IAAAAASUVORK5CYII=","orcid":"https://orcid.org/0009-0005-7004-4062","institution":"Maternité régionale de Nancy","correspondingAuthor":true,"prefix":"","firstName":"Océane","middleName":"","lastName":"Lalin","suffix":""},{"id":486513938,"identity":"6e843681-a6c6-489b-8fe5-4d6357f124b8","order_by":1,"name":"Jean-Marc Jelliman","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Jean-Marc","middleName":"","lastName":"Jelliman","suffix":""},{"id":486513939,"identity":"3f5bde3d-5239-42c1-b21e-0149763cd536","order_by":2,"name":"Jean-Michel HASCOET","email":"","orcid":"https://orcid.org/0000-0002-6335-3781","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Jean-Michel","middleName":"","lastName":"HASCOET","suffix":""}],"badges":[],"createdAt":"2025-07-11 10:10:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7100478/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7100478/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87371215,"identity":"6a5b1e71-0d7b-4137-8632-eeec42e1336b","added_by":"auto","created_at":"2025-07-23 07:12:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":21085,"visible":true,"origin":"","legend":"\u003cp\u003eFlow Chart\u003c/p\u003e\n\u003cp\u003eNICU : Neonatal intensive care unit\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7100478/v1/de1d7d3f47b03b03edd95cba.png"},{"id":88256586,"identity":"33d9d993-5c99-42f1-87f1-c525eda6e5a1","added_by":"auto","created_at":"2025-08-04 14:33:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":633737,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7100478/v1/4496108a-29fb-4a74-a678-9a81a4e4b4e3.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Clinical and echocardiographic response to volume expansion in hypotensive preterm infants","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eHemodynamic disturbances are common in preterm infants during the first hours of life. In clinical practice, this impairment in circulatory adaptation is usually identified by a drop in blood pressure, which tends to decrease in the first hours after birth.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) However, blood pressure measurement is only an approximate indicator of tissue perfusion, which also depends on cardiac output and heart rate. When these parameters are disturbed, there is a risk of cellular damage by tissue ischemia, followed by ischemia-reperfusion phenomena, particularly at the brain level (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eSimple clinical parameters used to detect tissue hypoperfusion include blood pressure, urine output, capillary refill time and heart rate. In addition, cardiac ultrasound is a simple, non-invasive method of hemodynamic assessment. It provides a pathophysiological perspective on hemodynamic disturbances and helps guide therapeutic choices. Neonatologists can easily analyze parameters such as shunts through the foramen ovale and ductus arteriosus, ventricular preload, ventricular function and possible pulmonary hypertension (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Superior vena cava (SVC) flow is another useful parameter, reflecting cerebral perfusion. It has been shown that when SVC flow is below 40 ml/kg/min, there is a clear risk of cerebral hypoperfusion and intraventricular hemorrhage in very premature infants. (\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eTreatment of these circulatory adaptation disorders is not standardized. In practice, optimization of ventricular preload by vascular filling is usually proposed as soon as arterial hypotension is present. However, this treatment has not been proven effective on tissue perfusion, and can be deleterious. It is relevant in case of hypovolemia, but this situation is not constant, and sometimes a vasopressor or inotropic treatment will be introduced as a first-line therapy. (\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eFilling products are numerous and classified as colloids or crystalloids. There is no official recommendation on the use of one filling solution or another(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Crystalloids include balanced solutions, ringer lactate and 0.9% NaCl. Colloids include blood-derived products such as concentrated red blood cells, albumin or modified fluid gelatin. Modified fluid gelatin 4 contains 150ml/L sodium and an osmolarity of 295 mOsm/Kg and may be used as an alternative to crystalloids in case of hypovolemic or vasoplegic shock. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eDecisions regarding volume expansion should integrate clinical, biological, and ultrasound criteria. Unwarranted volume expansion can lead to complications such as pulmonary hemorrhage, increased pulmonary shunt through PDA and foramen ovale, or excessive preload leading to pulmonary edema, Moreover, volume overload can contribute to cerebral hemorrhage due to elevated venous pressure, systolic and/or diastolic dysfunction, or impaired cerebral autoregulation.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eThe aim of this study is to identify what are the clinical and ultrasound impacts of volume expansion in the hypotensive preterm neonate in the first 24 hours of life.\u003c/p\u003e\u003cp\u003eThe clinical and echocardiographic impact, as well as short- and long-term complications, will be analyzed.\u003c/p\u003e"},{"header":"2. Material and Method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1.Type of Study:\u003c/h2\u003e\u003cp\u003eThis was a monocentric retrospective observational study carried out in the neonatal intensive care unit at the Nancy regional maternity hospital.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2.Study population :\u003c/h2\u003e\u003cp\u003eInclusion criteria were preterm infants between 26- and 31-weeks\u0026thinsp;+\u0026thinsp;6 days of gestation admitted over a 7 months period in the neonatal intensive care Unit at the Nancy Regional Maternity Hospital. The infants were intubated-ventilated presenting arterial hypotension during the first 24 hours of life (defined as mean arterial pressure (MAP) value below gestational age in completed weeks), and who received macromolecular volume expansion by modified fluid gelatin following echocardiography evaluation.\u003c/p\u003e\u003cp\u003eExclusion criteria were malformative heart disease other than persistent fetal shunts or small ventricular septal defect (VSD) of less than 2 mm diameter. Infants with diagnosed chromosomal abnormalities. Infant who had received prior hemodynamic treatment (vascular filling or vasopressor amines) were also excluded.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3.Data collection\u003c/h2\u003e\u003cp\u003eThe list of infants born very prematurely during the study period was obtained from the Medical Information Department of Nancy University Hospital. A table of correspondence (infant's name, date of birth, and anonymity number) was established and kept secure in an appropriate place (Office of the Head of Department). Only the infant's anonymity numbers appeared on the computer files created for the study (i.e., data collection, processing, and production of results). Data were collected from the hospitalization records, both computerized and paper files.\u003c/p\u003e\u003cp\u003eWe collected data on the first 24 hours of life, including vital signs: 3 blood pressure measurements with a cuff at 5 minutes, heart rate noted at each blood pressure measurement, infant's temperature, skin recoloration time.\u003c/p\u003e\u003cp\u003eUltrasound data from an ALOKA\u0026reg; ultrasound scanner, with a 7 MHz phased-array probe, included : heart morphology, foramen ovale (size, direction of shunt and velocity, in subcostal section), ductus arteriosus (size, direction of shunt, velocity, in supra-sternal section), left ventricular ejection fraction in left parasternal short axis, left ventricular end-diastolic diameter in the same section, the diameter of the (Inferior Vena Cava) IVC and the IVC respiratory variation index ((max diameter - min diameter) / (max diameter\u0026thinsp;+\u0026thinsp;min diameter) / 2) at the junction with the right atrium in longitudinal section of the IVC, SVC flow measurement (mean velocity over 8 cardiac cycles in subcostal section and mean measurement between maximum and minimum SVC diameter in high parasternal long-axis incidence, using the formula SVC flow (in ml/kg/min)\u0026thinsp;=\u0026thinsp;mean velocity in cm/s x π x (mean SVC radius in cm)2/weight in kg. Pulmonary pressures were assessed by measuring tricuspid insufficiency when present, and flow in the ductus arteriosus when open.\u003c/p\u003e\u003cp\u003eThese data were collected before and after volume expansion with Modified fluid gelatin at a dose of 20 ml/kg over 1 hour, according to the department's protocol at the time of inclusion.\u003c/p\u003e\u003cp\u003eData concerning the short- and medium-term evolution of the infant included hemodynamic management beyond vascular filling, and possible management of the ductus arteriosus (medical or surgical management), respiratory evolution with date of extubation and occurrence of bronchopulmonary dysplasia, occurrence of retinopathy and lesions on transfontanellar ultrasound, occurrence of ulcerative colitis and survival.\u003c/p\u003e\u003cp\u003e Our Institutional Review Board approved the study (Delegation \u0026agrave; la Recherche Clinique et \u0026agrave; l'Innovation du CHRU de Nancy ; DRCI number: n\u0026deg;2024PI174-531) Parents provided written consent for their infant's data to be used for research purposes.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4.Statistical analysis\u003c/h2\u003e\u003cp\u003eCategorical data are presented as numbers or percentages. Chi-squared was used to evaluate the differences between groups for categorical variables. Continuous variables that were not normally distributed are presented as medians with the interquartile range (IQR) and were analyzed using the Mann-Whitney U test. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant. All analyses were performed in SAS/STAT (Statistical Analysis System 9.4; 6th Edition).\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eThirty-one infants were analyzed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The median gestational age of these infants was 29 weeks (28;30) of amenorrhea, with a median weight of 1238(1218;1254). The median time from birth was 3 hours (2;5).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe characteristics of the population are presented Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\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\u003eCharacteristics of the population\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\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\u003eMedian(Q1\u0026nbsp;; Q3)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGestational age (week of amenorrhea)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (28 ; 30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight (g)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1238 (1218\u0026nbsp;; 1254)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eApgar 1 min\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (3\u0026nbsp;; 6.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eApgar 5 min\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (6\u0026nbsp;; 8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epH at the umbilical cord\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.295 (7.26\u0026nbsp;; 7.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLactic acid at the umbilical cord\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.9 (2.3\u0026nbsp;; 4.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIUGR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (10%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePremature rupture of membranes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (39%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecesarean section\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (65%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGeneral anesthesia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (20%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePeridural anesthesia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (70%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHyaline membrane disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (61%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003cem\u003eIUGR\u0026thinsp;=\u0026thinsp;Intrauterine Growth Restriction\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eVolume expansion had a significant influence, increasing systolic pressure by 6 mmHg (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), diastolic pressure by 3 mmHg (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), mean arterial pressure by 4 mmHg(p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), significantly decreasing heart rate by 10 bpm (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and capillary refill time (CRT) by 0.5 seconds (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEffect of volume expansion on clinical parameters\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore \u003c/p\u003e\u003cp\u003e(median (Q1\u0026nbsp;; Q3))\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAfter \u003c/p\u003e\u003cp\u003e(median (Q1\u0026nbsp;; Q3))\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSBP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (34.5\u0026nbsp;; 40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e43 (39.5\u0026nbsp;; 47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003eDBP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (15\u0026nbsp;; 19.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e20 (16.5\u0026nbsp;; 24.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003eMBP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (23\u0026nbsp;; 26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e28 (24.5\u0026nbsp;; 31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003eHR (bpm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e155 (144\u0026nbsp;; 171)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e145 (136.5\u0026nbsp;; 149)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003eCRT (s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.5 (2\u0026nbsp;; 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (1.5\u0026nbsp;; 2.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.0019\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eSBP\u0026thinsp;=\u0026thinsp;systolic blood pressure, DBP\u0026thinsp;=\u0026thinsp;diastoli cblood pressure, MBP\u0026thinsp;=\u0026thinsp;Mean blood pressure, HR\u0026thinsp;=\u0026thinsp;Heart rate, CRT\u0026thinsp;=\u0026thinsp;Capillary refill time\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eRegarding echocardiographic parameters, we observed a significantly faster mean velocity of the Left to right shunt in the PDA after volume expansion of 0.21 m/s (p\u0026thinsp;=\u0026thinsp;0.004), a significantly greater left ventricular end-diastolic diameter of 1.3 mm (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), a significantly greater mean velocity in the left pulmonary artery of 0.09 m/s (p\u0026thinsp;=\u0026thinsp;0.01), a significantly greater superior vena cava diameter of 0.6 mm(p\u0026thinsp;=\u0026thinsp;0.0001) and a significantly greater flow at the superior vena cava output of 16.2 ml/kg/min (p\u0026thinsp;=\u0026thinsp;0.02) (Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEffect of volume expansion on echocardiographic parameters\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\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=\"left\" 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=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\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\u003ebefore\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eafter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePDA\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eyes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 (96%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ediameter (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.8 (1.3\u0026nbsp;; 2.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.5 (1.15\u0026nbsp;; 2.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eshunt direction\u003c/p\u003e\u003cp\u003e- LR\u003c/p\u003e\u003cp\u003e- Bidirectionnal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (37%)\u003c/p\u003e\u003cp\u003e19 (63%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (40%)\u003c/p\u003e\u003cp\u003e18 (60%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eshunt LR velocity (m/s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.86 (0.55\u0026nbsp;; 1.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.07 (0.8\u0026nbsp;; 1.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eshunt RL velocity (m/s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.34 (0-0.64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.39 (0\u0026nbsp;; 0.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eright-left time to cycle ratio\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.16 (0\u0026nbsp;; 0,285)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.17 (0\u0026nbsp;; 0.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.63\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esystemic pulmonary arterial pressure (mmhg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34 (31\u0026nbsp;; 38.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e37 (34\u0026nbsp;; 41.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.05\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esystemic pulmonary arterial pressure (mmhg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (23.5\u0026nbsp;; 33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e33 (30\u0026nbsp;; 36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePFO\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eyes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (84%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28 (93%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emeasure (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2,3 (1.6\u0026nbsp;; 2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.5 (1.5\u0026nbsp;; 3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLR shunt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (20%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBidirectionnal shunt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (80%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (57%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eshunt LR velocity (m/s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.36 (0.2\u0026nbsp;; 0.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.57 (0.48\u0026nbsp;; 0.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eshunt RL velocity (m/s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.16 (0\u0026nbsp;; 0.225)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.12 (0\u0026nbsp;; 0.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLVEF\u003c/b\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e75 (71.5\u0026nbsp;; 80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e75.5 (70.7\u0026nbsp;; 79.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eleft ventricular end-diastolic diameter\u003c/b\u003e (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11.6 (11.05\u0026nbsp;; 12.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.9 (11.9\u0026nbsp;; 13.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean velocity of left pulmonary artery (m/s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.35 (0.3\u0026nbsp;; 0.42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.44 (0.37\u0026nbsp;; 0.47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInferior vena cava\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003evariability index\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.25 (0.13\u0026ndash;0.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.20 (0.09\u0026nbsp;; 0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.59\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSuperior vena cava\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMax. diameter (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.4 (2.8\u0026nbsp;; 3.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (3.2\u0026nbsp;; 4.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean velocity (m/s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.20 (0.15\u0026nbsp;; 0,25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.20 (0.16\u0026nbsp;; 0.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.74\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eoutput (ml/kg/min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e82.8 (48.8\u0026nbsp;; 104.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e99 (66.3\u0026nbsp;; 99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cem\u003ePDA\u0026thinsp;=\u0026thinsp;Patent Ductus Arteriosus, LR\u0026thinsp;=\u0026thinsp;Left to Right, RL\u0026thinsp;=\u0026thinsp;Right to Left, TR\u0026thinsp;=\u0026thinsp;Tricuspide regurgitation, PFO\u0026thinsp;=\u0026thinsp;Patent Foramen Ovale, LVEF\u0026thinsp;=\u0026thinsp;Left Ventricular Ejection Fraction\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThere was no significant difference between CRT, ultrasound parameters and CRT normalization.\u003c/p\u003e\u003cp\u003eFollowing a first volume expansion, 15 infants (48%) required further volume expansion, they all also received vasopressor support with Dopamine and Dobutamine. None of them received hydrocortisone hemisuccinate.\u003c/p\u003e\u003cp\u003eThere was no significant difference between the medium- and long-term evolution and the normalization of CRT after filling: there were 11 infants with CRT\u0026thinsp;\u0026gt;\u0026thinsp;or equal to 3 seconds, in this group, none required oxygen at 28 days versus 12 in the CRT\u0026thinsp;\u0026lt;\u0026thinsp;3 seconds group p\u0026thinsp;=\u0026thinsp;0.43, 1 received ibuprofen treatment in the CRT\u0026thinsp;\u0026gt;\u0026thinsp;or equal to 3 seconds group and 2 in the \u0026lt;\u0026thinsp;3 seconds group (p\u0026thinsp;=\u0026thinsp;1). 2 infants in each group had HIV (p\u0026thinsp;=\u0026thinsp;0.61). Also, 1 infant presented with retinopathy in the CRT\u0026thinsp;\u0026gt;\u0026thinsp;or equal to 3 seconds group and 2 in the \u0026lt;\u0026thinsp;3 seconds group (p\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e\u003cp\u003eThere was also no significant difference in the persistence of hypotension after filling and medium- and long-term evolution.\u003c/p\u003e\u003cp\u003eThe medium- and long-term complications of the patients analyzed are presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComplications by patients treated\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBPD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (53%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emoderate BPD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (40%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMid BPD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (6.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSevere BPD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (6.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePDA tretaed by ibuprophen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (10%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePDA treated by surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIVH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (13%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIVH I\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (10%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIVH II\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIVH III\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIVH IV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRetinopathy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUlceronecrotizing enterocolitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (10%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDeath\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003cem\u003eBPD\u0026thinsp;=\u0026thinsp;bronchopulmonary dysplasia, IVH\u0026thinsp;=\u0026thinsp;Intraventricular Haemorrhage\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eNICU : Neonatal intensive care unit\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eOur study showed that volume expansion with 20 ml/kg of modified fluid gelatin in case of arterial hypotension in very preterm neonates significantly improved systolic, mean, and diastolic blood pressure, as well as heart rate and CRT normalization. Volume expansion significantly increase left ventricular end-diastolic diameter (LVEDD), superior vena cava (SVC) flow, and heart rate also increased significantly following volume administration.\u003c/p\u003e\u003cp\u003eHeart rate significantly decreased post-expansion. Since cardiac output is the product of heart rate and stroke volume, tachycardia is often a compensatory response to hypovolemia-induced stroke volume reduction. However, isolated tachycardia should not automatically prompt volume expansion; other causes must be investigated if hemodynamic failure is absent.\u003c/p\u003e\u003cp\u003eWe observed a significant reduction in CRT following volume expansion. CRT serves as an objective marker of skin microcirculation, yet ultrasound findings did not show differences in volume expansion response between neonates with CRT\u0026thinsp;\u0026ge;\u0026thinsp;3s and those with CRT\u0026thinsp;\u0026lt;\u0026thinsp;3s. Prior research suggests that CRT alone is an insufficient predictor of low systemic blood flow; its correlation with ascending aortic flow remains weak (r2\u0026thinsp;=\u0026thinsp;0.54) (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Similarly, Osborn et al. demonstrated a poor positive predictive value for detecting low SVC flow (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Instead, CRT should be used alongside other clinical, biological, and echocardiographic parameters. In 2008, Miletin et al. showed that combining SVC flow measurement with CRT\u0026thinsp;\u0026gt;\u0026thinsp;4s has a positive predictive value of 100% for adverse outcomes such as hypoxic-ischemic encephalopathy (HIE) or death. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eOur findings confirm a significant increase in LVEDD after volume expansion. LVEDD reflects ventricular preload, yet its measurement is highly dependent on optimal ultrasound technique. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eSVC flow significantly increased post-expansion (p\u0026thinsp;=\u0026thinsp;0.01), yet no correlation was found between SVC flow and blood pressure. Kluckow et al. (2004) identified SVC flow\u0026thinsp;\u0026lt;\u0026thinsp;40 ml/kg/min as predictive of HIE or poor neurological outcomes at 3 years (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). However, SVC flow measurement is technically challenging and requires expertise in neonatal echocardiography.\u003c/p\u003e\u003cp\u003eInferior vena cava (IVC) size did not significantly change after volume expansion. While IVC measurement is widely used to estimate blood volume (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), our findings may be explained by the fact that most neonates in the study were under mechanical ventilation. High PEEP ventilation can increase IVC size while reducing its compliance, complicating its interpretation. Nevertheless, IVC assessment remains useful for neonates on spontaneous ventilation. This may be different nowadays, as premature infants are less likely to undergo invasive ventilation due to hydrocortisone hemisuccinate supplementation as per the PREMILOC protocol.(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eHemodynamic management in very preterm neonates is complex, blood pressure assessment should distinguish between systolic, diastolic, and mean arterial pressure. Postnatal adaptation involves increased pulmonary blood flow due to reduced pulmonary vascular resistance, leading to higher pulmonary venous return and increased preload, which elevates systolic blood pressure. However, if a patent ductus arteriosus (PDA) persists, a diastolic steal effect may occur, reducing diastolic and mean arterial pressure. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eHypovolemia can lead to low flow, which in turn is responsible for hemodynamic failure, with reduced mean arterial pressure and peripheral hypoperfusion.(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) However, various clinical and biological parameters must be taken into account, not just mean arterial pressure to evaluate tissue perfusion in neonatology. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)We did not study diuresis, consciousness, respiratory mechanics and saturation, which are also important data to analyze when talking about hemodynamic failure.) (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eCompared with the literature(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e), there were no early or late complications in the group of premature infants who received modified fluid gelatin volume expansion within the first 24 hours of life. Volemic expansion could therefore be carried out without risk in the event of the ultrasound machine being unavailable in the presence of signs of peripheric hypoperfusion in the newborn.\u003c/p\u003e\u003cp\u003eOur study presents limitations, first, it was a single-center observational study with a small sample size. Then, modified fluid gelatin, the colloid used, is no longer recommended in clinical practice. In addition, we did not collect biochemical markers or clinical variables such as urine output, consciousness level, respiratory mechanics, and oxygen saturation.\u003c/p\u003e\u003cp\u003eWhile no adverse effects were noted, our study is not sufficient to definitively affirm the safety of volume expansion. However, the existing literature has not clearly demonstrated significant risks associated with this intervention. Another limitation is the absence of a control group, which limits our ability to compare the observed hemodynamic improvements to spontaneous postnatal adaptation. However, in the presence of hemodynamic failure, a control group would not be ethical.\u003c/p\u003e\u003cp\u003eModern neonatal care has evolved, with fewer preterm neonates requiring intubation due to improved volume status (delayed cord clamping or umbilical milking) and better vascular resistance management with hydrocortisone therapy. This evolving context should be considered when applying our findings to current practice.\u003c/p\u003e\u003cp\u003eDespite these limitations, our study has notable strengths, Echocardiographic assessments were performed by experienced sonographers The same ultrasound equipment was used for all measurements, ensuring consistency. Data collection followed a standardized protocol.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThese findings justify not hesitating to perform volume expansion in preterm within the first 24 hours of life, when deemed necessary, particularly in sedated, intubated, and ventilated neonates, as in our cohort\u003c/p\u003e\u003cp\u003eVolemic expansion has positive impact on mean arterial pressure, systolic arterial pressure, diastolic arterial pressure, LVEDD and superior vena cava flow, heart rate and CRT\u003c/p\u003e\u003cp\u003eCRT measurements are not correlated with ultrasound measurements.\u003c/p\u003e\u003cp\u003eIf ultrasound is not available, it therefore seems reasonable to optimize blood volume before introducing other therapies in the event of hemodynamic failure.\u003c/p\u003e\u003cp\u003eIt would be interesting to carry out this study with the filling products currently in use, and to analyze their effectiveness in combination with the various factors mentioned above.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Professor Rachel Vieux for the statistical analysis of the data\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding sources\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The authors declare no conflicts of interes\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDasgupta SJ. Hypotension in the very low birthweight infant: the old, the new, and the uncertain. Arch Dis Child - Fetal Neonatal Ed. 1 nov 2003;88(6):450F ‑ 454.\u003c/li\u003e\n\u003cli\u003eLee J, Rajadurai VS, Tan KW. Blood pressure standards for very low birthweight infants during the first day of life. Arch Dis Child - Fetal Neonatal Ed. 1 nov 1999;81(3):F168‑70.\u003c/li\u003e\n\u003cli\u003eCayabyab R, McLean CW, Seri I. Definition of hypotension and assessment of hemodynamics in the preterm neonate. J Perinatol. mai 2009;29(S2):S58‑62.\u003c/li\u003e\n\u003cli\u003eLalin O, Gaga S, Hascoet JM. Management Practices for Hemodynamic Impairment in Neonates Born Prematurely: A Quality Improvement Project. J Clin Med. 14 nov 2024;13(22):6848.\u003c/li\u003e\n\u003cli\u003eKluckow M. Use of ultrasound in the haemodynamic assessment of the sick neonate. Arch Dis Child - Fetal Neonatal Ed. juill 2014;99(4):F332‑7.\u003c/li\u003e\n\u003cli\u003eMiletin J, Dempsey EM. Low superior vena cava flow on day 1 and adverse outcome in the very low birthweight infant. Arch Dis Child - Fetal Neonatal Ed. 1 sept 2008;93(5):F368‑71.\u003c/li\u003e\n\u003cli\u003eKluckow M. Superior vena cava flow in newborn infants: a novel marker of systemic blood flow. Arch Dis Child - Fetal Neonatal Ed. 1 mai 2000;82(3):182F ‑ 187.\u003c/li\u003e\n\u003cli\u003eKluckow M. Low superior vena cava flow and intraventricular haemorrhage in preterm infants. Arch Dis Child - Fetal Neonatal Ed. 1 mai 2000;82(3):188F ‑ 194.\u003c/li\u003e\n\u003cli\u003eDepartment of Neonatology, University of Health Sciences, Dr. Sami Ulus Maternity and Children\u0026rsquo;s Training and Research Hospital, Ankara, Turkey, Dilli D, Soylu H, Division of Neonatology, Department of Pediatrics, Selcuk University, Faculty of Medicine, Konya, Turkey, Tekin N, Division of Neonatology, Department of Pediatrics, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey. Turkish Neonatal Society guideline on the neonatal hemodynamics and management of hypotension in newborns. T\u0026uuml;rk Pediatri Arş. 22 f\u0026eacute;vr 2019;53(sup1):65‑75.\u003c/li\u003e\n\u003cli\u003eJoynt C, Cheung PY. Treating Hypotension in Preterm Neonates With Vasoactive Medications. Front Pediatr. 13 avr 2018;6:86.\u003c/li\u003e\n\u003cli\u003eOsborn DA, Evans NJ. Early volume expansion for prevention of morbidity and mortality in very preterm infants. Cochrane Neonatal Group, \u0026eacute;diteur. Cochrane Database Syst Rev [Internet]. 19 avr 2004 [cit\u0026eacute; 30 nov 2024]; Disponible sur: https://doi.wiley.com/10.1002/14651858.CD002055.pub2\u003c/li\u003e\n\u003cli\u003eWu TW, Noori S. Recognition and management of neonatal hemodynamic compromise. Pediatr Neonatol. f\u0026eacute;vr 2021;62:S22‑9.\u003c/li\u003e\n\u003cli\u003eUpadhyay M, Singhi S, Kaur N, Majumdar S. Randomized evaluation of fluid resuscitation with crystalloid (saline) and colloid (polymer from degraded gelatin in saline) in pediatric septic shock. Indian Pediatr. 2005;(IMar;42(3):223-31.).\u003c/li\u003e\n\u003cli\u003eGrace E, Keir AK. Fluid Therapy. Clin Perinatol. sept 2020;47(3):515‑28.\u003c/li\u003e\n\u003cli\u003eWeaver LJ, Travers CP, Ambalavanan N, Askenazi D. Neonatal fluid overload\u0026mdash;ignorance is no longer bliss. Pediatr Nephrol. janv 2023;38(1):47‑60.\u003c/li\u003e\n\u003cli\u003eEwer AK, Tyler W, Francis A, Drinkall D, Gardosi JO. Excessive volume expansion and neonatal death in preterm infants born at 27\u0026ndash;28 weeks gestation. Paediatr Perinat Epidemiol. avr 2003;17(2):180‑6.\u003c/li\u003e\n\u003cli\u003eWodey, Eric MD; Pladys, Patrick MD; Betremieux, Pierre MD; Kerebel, Christine MD; Ecoffey, Claude MD. Capillary refilling time and hemodynamics in neonates: A Doppler echocardiographic evaluation. Critical Care Medicine 26(8):p 1437-1440, August 1998.\u003c/li\u003e\n\u003cli\u003eMiletin J, Pichova K, Dempsey EM. Bedside detection of low systemic flow in the very low birth weight infant on day 1 of life. Eur J Pediatr. juill 2009;168(7):809‑13.\u003c/li\u003e\n\u003cli\u003eMcNamara PJ, Jain A, El-Khuffash A, Giesinger R, Weisz D, Freud L, et al. Guidelines and Recommendations for Targeted Neonatal Echocardiography and Cardiac Point-of-Care Ultrasound in the Neonatal Intensive Care Unit: An Update from the American Society of Echocardiography. J Am Soc Echocardiogr. f\u0026eacute;vr 2024;37(2):171‑215.\u003c/li\u003e\n\u003cli\u003eLopez L, Saurers DL, Barker PCA, Cohen MS, Colan SD, Dwyer J, et al. Guidelines for Performing a Comprehensive Pediatric Transthoracic Echocardiogram: Recommendations From the American Society of Echocardiography. J Am Soc Echocardiogr. f\u0026eacute;vr 2024;37(2):119‑70.\u003c/li\u003e\n\u003cli\u003eBaud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C, et al. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. The Lancet. avr 2016;387(10030):1827‑36.\u003c/li\u003e\n\u003cli\u003eGupta S, Donn SM. Assessment of neonatal perfusion. Semin Fetal Neonatal Med. oct 2020;25(5):101144.\u003c/li\u003e\n\u003cli\u003eCarrapato MRG, Andrade T, Caldeira T. Hypotension in small preterms: what does it mean? J Matern Fetal Neonatal Med. 2 d\u0026eacute;c 2019;32(23):4016‑21.\u003c/li\u003e\n\u003cli\u003eJensen EA, Schmidt B. Epidemiology of bronchopulmonary dysplasia. Birt Defects Res A Clin Mol Teratol. mars 2014;100(3):145‑57.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"preterm, hemodynamic impairment, volume expansion, Ultrasound","lastPublishedDoi":"10.21203/rs.3.rs-7100478/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7100478/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: Hemodynamic instability is common in preterm neonates. Volume expansion remains controversial due to its uncertain efficacy and potential adverse effects. The objective was to evaluate the effects of volume expansion in preterm infants with hypotension within 24 hours of birth.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e: Retrospective study of preterm neonates receiving modified fluid gelatin for hypotension. Clinical and echocardiographic parameters were compared before and after treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: In 31 infants, volume expansion significantly increased systolic, diastolic, and mean arterial pressures (mean increase: +6, +3, +4 mmHg respectively; p \u0026lt; 0.0001), and decreased heart rate (−10 bpm) and capillary refill time (−0.5 s; p \u0026lt; 0.0001). Improved echocardiographic markers of preload and output included Left Ventricular End-Diastolic Diameter (+1.3 mm), Superior Vena Cava flow (+16.2 ml/kg/min), and ductus arteriosus shunt velocity (+0.21 m/s). No adverse effects were reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Volume expansion improved clinical and echocardiographic parameters in hypotensive preterm infants without observed complications.\u003c/p\u003e","manuscriptTitle":"Clinical and echocardiographic response to volume expansion in hypotensive preterm infants","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-23 07:04:44","doi":"10.21203/rs.3.rs-7100478/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c305044d-06da-4a7b-af59-ad24fa19c8d9","owner":[],"postedDate":"July 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":51651344,"name":"Health sciences/Medical research/Outcomes research"},{"id":51651345,"name":"Health sciences/Health care/Paediatrics"}],"tags":[],"updatedAt":"2025-08-04T14:25:26+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-23 07:04:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7100478","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7100478","identity":"rs-7100478","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}