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Baranowski ES, Idkowiak J, Waterson J, D'Harlingue A, Olney AH, Ivison HE, Hughes BA, Mueller JW, Arlt W, Shackleton CHL. The distinctive P450 oxidoreductase (PORD) urinary steroid metabolome in the first week of life: Report of three cases with severe disorder. J Steroid Biochem Mol Biol 2025; 251:106760. [PMID: 40222686 DOI: 10.1016/j.jsbmb.2025.106760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 03/28/2025] [Accepted: 04/10/2025] [Indexed: 04/15/2025]
Abstract
P450 oxidoreductase (POR) facilitates electron flux to type 2 microsomal P450 cytochrome enzymes (CYPs), including the adrenal steroidogenic enzymes CYP17A1 and CYP21A2. Due to the combined impairment of these enzymes, POR deficiency (PORD), an autosomal recessive condition, results in congenital adrenal hyperplasia characterised by combined glucocorticoid and postnatal sex steroid deficiency. This study focuses on urinary steroid excretion in infants affected by PORD in the first week of life. We report on three neonatal PORD cases from two families. One family had two affected babies born three years apart who were stillborn and first-day deceased, respectively. DNA sequencing revealed a homozygous 3 bp deletion in exon six leading to an glutamic acid deletion (p.[Glu217del]). Bladder contents were obtained from the stillborn baby, and excreted urine was obtained from the second baby. In a second family, their second affected newborn, antenatally diagnosed carrying the common homozygous p.(Ala287Pro) mutation, had urine collected daily during the first week of life. Steroid excretions were quantified by gas chromatography-mass spectrometry (GC-MS). The birth-day excretions were very similar in all babies. Most notable and unusual was a large excretion of unmetabolised corticosterone, suggesting inhibited catabolism to allow maximum active gluco- and mineralocorticoid availability at birth. Because CYP3A7 (16α-hydroxylase) requires POR, there was an almost complete absence of usually dominant 3β-hydroxy-Δ5 steroids (16α-OH-DHEA and 16α-OH-pregnenolone) and the usually characteristic precursor pregnenolone metabolite 5-pregnene-3β,20α-diol (pregnenediol, 5PD). In the baby sequentially studied over a week, we observed gradual maturation to the typical and familiar PORD neonatal metabolome. At the end of the period, the minimally catabolised corticosterone had diminished, and steroid excretion was completely dominated by 5PD, excreted as both mono- and disulphate conjugates. Whether this metabolome is distinctive of all PORD infants, not just those with severe manifestation, is not known. On the first day of life, standard diagnostic markers are compromised due to fetal-placental-maternal contribution and unique neonatal steroid metabolism. However, the Day 1 PORD steroid metabolome remains distinctive, and we propose using additional biochemical markers reflective of the near complete reduction of POR-dependent CYP3A7 (16α-hydroxylase) activity to improve diagnostic yield.
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Affiliation(s)
- E S Baranowski
- Department of Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, UK; Department of Endocrinology and Diabetes, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
| | - J Idkowiak
- Department of Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, UK; Department of Endocrinology and Diabetes, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK; NIHR Birmingham Biomedical Research Centre (BRC), Women's Metabolic Health Theme, University of Birmingham, UK.
| | - J Waterson
- UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA
| | - A D'Harlingue
- UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA
| | - A H Olney
- University of Nebraska Medical Center, Omaha, NE, USA
| | - H E Ivison
- Department of Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, UK
| | - B A Hughes
- Department of Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, UK
| | - J W Mueller
- Department of Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, UK
| | - W Arlt
- Department of Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK; Medical Research Council Laboratory of Medical Sciences (MRC LMS), London, UK; Institute of Clinical Sciences, Imperial College London, London, UK
| | - C H L Shackleton
- Department of Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK; UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA
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Ozkan H, Duman N, Tuzun F, Narter F, Akyildiz C, Altuncu E, Satar M, Ozdemir M, Kurt A, Tugcu AU, Konak M, Uygun SS, Yilmaz Semerci S, Dikmen RT, Baysal B, Zeybek CK, Kostekci YE, Sahin S, Tutal M, Anik A, Buyuktiryaki M, Karagol BS, Tunç G, Colak D, Cetin H, Orman A, Olukman O, Deveci MF, Sarici D, Cakir SC, Keskinoglu P. The efficacy and safety of isotonic and hypotonic fluids in intravenous maintenance fluid therapy in term newborns: national multicenter observational "neofluid" study. Front Nutr 2024; 11:1410571. [PMID: 39376791 PMCID: PMC11457840 DOI: 10.3389/fnut.2024.1410571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 08/29/2024] [Indexed: 10/09/2024] Open
Abstract
Objective The objective of this study was to evaluate the efficacy and safety of isotonic and hypotonic intravenous fluids in maintenance fluid therapy for term infants. Methods This was a multi-centre, prospective, observational study conducted in 21 participating centres from December 30, 2020, to June 30, 2023. The study included term newborns requiring parenteral fluid therapy for maintenance (NCT04781361). The fluid treatment was divided into two groups based on the concentration of sodium in the parenteral fluid, designated as hypotonic (NaCl <130 mmol/L) and isotonic (NaCl = 130-154 mmol/L). The primary outcomes were the change in mean plasma sodium (pNa) levels per hour (∆pNa mmol/L/h), the incidence of hyponatremia (pNa <135 mmol/L) and hypernatremia (pNa >145 mmol/L), and the occurrence of clinically significant changes in sodium levels (∆pNa >0.5 mmol/L/h). Results A total of 420 patients from 21 centers were included. The ∆pNa was negative in the hypotonic fluid group and positive in the isotonic fluid group, with a significant difference between the groups [respectively -0.07 ± 0.03 (95% CI: -0.13 to -0.02); 0.04 ± 0.03 (95%CI: -0.02 to 0.09), p = 0.04]. There was no difference between the groups in terms of the development of hypernatremia or a clinically meaningful pNa increase. The hypotonic fluid group had a higher incidence of hyponatremia and a clinically meaningful sodium decrease compared to the isotonic fluid group [7.9% vs. 1.2% (OR:6.5, p:0.03)] and [12.2% vs.4.2% (OR:2.9, p = 0.03)]. Conclusion Contrary to current understanding, this large-scale study is the first to demonstrate that the use of hypotonic fluids in maintenance fluid therapy for newborns poses a risk of hyponatremia development, whereas isotonic fluid therapy appears safe.
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Affiliation(s)
- Hasan Ozkan
- Faculty of Medicine, Dokuz Eylül University, Izmir, Türkiye
| | - Nuray Duman
- Faculty of Medicine, Dokuz Eylül University, Izmir, Türkiye
| | - Funda Tuzun
- Faculty of Medicine, Dokuz Eylül University, Izmir, Türkiye
| | - Fatma Narter
- Istanbul Kartal Dr.Lutfi Kirdar Education and Research Hospital, Istanbul, Türkiye
| | - Can Akyildiz
- Faculty of Medicine, Dokuz Eylül University, Izmir, Türkiye
| | - Emel Altuncu
- Istanbul Kartal Dr.Lutfi Kirdar Education and Research Hospital, Istanbul, Türkiye
| | - Mehmet Satar
- Faculty of Medicine, Cukurova University, Adana, Türkiye
| | | | - Abdullah Kurt
- Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Türkiye
| | - Ali U. Tugcu
- Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Türkiye
| | - Murat Konak
- School of Medicine, Selcuk University, Konya, Türkiye
| | | | - Seda Yilmaz Semerci
- University of Health Sciences, Istanbul Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Türkiye
| | - Rahime T. Dikmen
- İstanbul Kanuni Sultan Süleyman Eğitim ve Araştırma Hastanesi, Istanbul, Türkiye
| | - Bora Baysal
- Faculty of Medicine, Uşak University, Usak, Türkiye
| | | | | | - Suzan Sahin
- Department of Pediatrics, Division of Neonatology, Aydın Maternity and Children Hospital, Aydin, Türkiye
| | - Merve Tutal
- Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir, Türkiye
| | - Ayse Anik
- Medical School, Adnan Menderes University, Aydin, Türkiye
| | - Mehmet Buyuktiryaki
- School of International Medicine, Istanbul Medipol University, Istanbul, Türkiye
| | - Belma S. Karagol
- Gulhane Faculty of Medicine, University of Health Sciences, Ankara, Türkiye
| | - Gaffari Tunç
- School of Medicine, Cumhuriyet University, Sivas, Türkiye
| | - Derya Colak
- Umraniye Research and Training Hospital, University of Health Sciences, Istanbul, Türkiye
| | - Hasan Cetin
- School of Medicine, Süleyman Demirel University, Isparta, Türkiye
| | - Aysen Orman
- Faculty of Medicine, Mersin University, Isparta, Türkiye
| | - Ozgur Olukman
- Faculty of Medicine, İzmir Bakircay University, İzmir, Türkiye
| | | | - Dilek Sarici
- S.B. Keçiören Eğitim ve Araştırma Hastanesi, Malatya, Türkiye
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Röher K, Fideler F. Update on perioperative fluids. Best Pract Res Clin Anaesthesiol 2024; 38:118-126. [PMID: 39445557 DOI: 10.1016/j.bpa.2024.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 03/05/2024] [Indexed: 10/25/2024]
Abstract
Adequate fluid management in the perioperative period in paediatric patients is essential for restoring and maintaining homeostasis and ensuring adequate tissue perfusion. A well-designed infusion regimen is crucial for preventing severe complications such as hyponatraemic encephalopathies. The composition of perioperative fluid solutions is now guided by an understanding of extracellular fluid physiology. Various crystalloid and colloidal products are available for use, but a comprehensive approach requires careful consideration of their drawbacks and limitations. Additionally, the unique characteristics of different patient groups must be taken into account. This review will provide the reader with physiological considerations for perioperative fluids and describe indications for perioperative intravenous fluid therapy in paediatric patients. The current evidence on perioperative fluid therapy is finally summarised in practical recommendations.
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Affiliation(s)
- Katharina Röher
- Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
| | - Frank Fideler
- Department of Anesthesiology and Intensive Care Medicine, University Hospital of Tuebingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany
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Marin T, Dowell SH, Wright K, Mansuri A, Mann PC. Late-Onset Hyponatremia in Premature Infants. J Perinat Neonatal Nurs 2023; 37:325-331. [PMID: 37115978 DOI: 10.1097/jpn.0000000000000737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Abstract
Late-onset hyponatremia (LOH) frequently affects premature infants 2 or more weeks of age due to inadequate sodium intake and excessive kidney loss. Late-onset hyponatremia typically occurs in infants who are physiologically stable and is defined as serum sodium of 132 mEq/L or less or between 133 and 135 mEq/L if receiving sodium supplementation. Recent evidence suggests that spot urine sodium levels may improve the recognition of LOH, as low levels of excreted urine reflect a total body sodium deficit and negative balance. Untreated LOH may result in poor somatic growth, neurodevelopmental delay, higher incidence of bronchopulmonary dysplasia, and more severe retinopathy of prematurity. The primary prevention of LOH is to maintain serum sodium between 135 and 145 mEq/L; however, there are currently no formal protocols guiding sodium supplementation. The purpose of this article is to present on overview of LOH pathophysiology and its effect on somatic growth, neurodevelopment outcomes, and other related sequelae. We further discuss general management strategies and describe a protocol for sodium supplementation that is presently undergoing an evaluation for effectiveness.
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Affiliation(s)
- Terri Marin
- Department of Nursing Science, Augusta University, College of Nursing, Augusta, Georgia (Dr Marin); and Departments of Pediatric Nephrology (Dr Mansuri) and Pediatrics, Division of Neonatology (Dr Mann), Medical College of Georgia, Augusta University (Mr Dowell and Ms Wright)
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Kronborg JR, Lindhardt RB, Vejlstrup N, Holst LM, Juul K, Smerup MH, Gjedsted J, Ravn HB. Postoperative free water administration is associated with dysnatremia after congenital heart disease surgery in infants. Acta Anaesthesiol Scand 2023; 67:730-737. [PMID: 36866603 DOI: 10.1111/aas.14223] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 02/01/2023] [Accepted: 02/06/2023] [Indexed: 03/04/2023]
Abstract
Dysnatremia after congenital heart disease (CHD) surgery is common. European guidelines on intraoperative fluid therapy in children recommend isotonic solutions to avoid hyponatremia, but prolonged cardiopulmonary bypass and administration of high sodium-containing solutions (i.e., blood products and sodium bicarbonate) are associated with postoperative hypernatremia. The aim of the study was to describe fluid composition prior to and during the development of postoperative dysnatremia. A retrospective observational, single-center study including infants undergoing CHD surgery. Demographics and clinical characteristics were registered. Highest and lowest plasma sodium values were recorded and associations with perioperative fluid administration, blood products, crystalloids, and colloids were explored in relation to three perioperative periods. Postoperative dysnatremia occurred in nearly 50% of infants within 48 h after surgery. Hypernatremia was mainly associated with administration of blood products (median [IQR]: 50.5 [28.4-95.5] vs. 34.5 [18.5-61.1] mL/kg; p = 0.001), and lower free water load (1.6 [1.1-2.2] mL/kg/h; p = 0.01). Hyponatremia was associated with a higher free water load (2.3 [1.7-3.3] vs. 1.8 [1.4-2.5] mL/kg/h; p = 0.001) and positive fluid balance. On postoperative day 1, hyponatremia was associated with higher volumes of free water (2.0 [1.5-2.8] vs. 1.3 [1.1-1.8] mL/kg/h; p < 0.001) and human albumin, despite a larger diuresis and more negative daily fluid balance. Postoperative hyponatremia occurred in 30% of infants despite restrictive volumes of hypotonic maintenance fluid, whereas hypernatremia was mainly associated with blood product transfusion. Individualized fluid therapy, with continuous reassessment to reduce the occurrence of postoperative dysnatremia is mandatory in pediatric cardiac surgery. Prospective studies to evaluate fluid therapy in pediatric cardiac surgery patients are warranted.
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Affiliation(s)
- Jonas Rønne Kronborg
- Department of Cardiothoracic Anesthesiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Rasmus Bo Lindhardt
- Department of Cardiothoracic Anesthesiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Niels Vejlstrup
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Line Marie Holst
- Department of Pediatrics, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark
| | - Klaus Juul
- Department of Pediatric Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Morten Holdgaard Smerup
- Department of Cardiothoracic Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Jakob Gjedsted
- Department of Cardiothoracic Anesthesiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Hanne Berg Ravn
- Department of Cardiothoracic Anesthesiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Anesthesiology and Intensive Care, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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McGregor K, McConnell C. Principles of anaesthesia for term neonates. ANAESTHESIA & INTENSIVE CARE MEDICINE 2022. [DOI: 10.1016/j.mpaic.2022.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Abstract
Optimal hydration is required for all physiologic functions and cognition. Children, especially younger ones, are particularly susceptible to dehydration, given their physiological specificities, in particular, their renal immaturity and relatively large skin surface in early life, but also their dependence on adults and their greater propensity to develop digestive diseases leading to fluid losses. Mild dehydration consequences are dominated by their impact on cognitive functions, whereas more severe dehydration may endanger the health outcome. Studies on this subject in children are scarce; in particular, the long-term consequence on renal function remains questionable. This review considers how children's water intake including fluid intake and water content of food, are worrying. The findings show that, worldwide, most children do not meet adequate water intake recommendations. The main problems likely to explain insufficient water intake are access to safe water, availability of drinking water at school, and healthy-hydration education, which are all points that need to be improved within health policy.
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Affiliation(s)
- Jean-Pierre Chouraqui
- Paediatric Nutrition and Gastroenterology, Division of Pediatrics, Woman, Mother and Child Department, Pediatric Nutrition and Gastroenterology Unit, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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Kochanowicz JF, Nowicka A, Al-Saad SR, Karbowski LM, Gadzinowski J, Szpecht D. Catheter-related bloodstream infections in infants hospitalized in neonatal intensive care units: a single center study. Sci Rep 2022; 12:13679. [PMID: 35953522 PMCID: PMC9372030 DOI: 10.1038/s41598-022-17820-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 08/01/2022] [Indexed: 11/09/2022] Open
Abstract
Sepsis in neonates carries a high morbidity and mortality rate and is among the most feared complications in the neonatal intensive care unit (NICU). Catheter-related bloodstream infections (CRBSI) are a common etiology of late-onset sepsis. The aim of this study was to compare risk factors and characteristics between patients according to the type of catheter that was utilized and according to birth weight classification. The study included 51 newborns with confirmed CRBSI, which were hospitalized in our level 3 NICU between January 2017 and December 2018. The study population was stratified according to the type of venous catheter utilized (peripherally inserted central catheter, central venous catheter (CVC), and peripheral venous catheter). Infants with low birth weight and those who required prolonged parenteral nutrition were most likely to develop CRBSI in our study group. The type of venous catheter was not associated with blood culture results. Also, infants with a birth weight of < 1500 g and > 1500 g did not differ in sepsis etiology. Further research is required to assess venous catheters relative risk of causing sepsis and if the outcome can be traced back specifically to catheter type or patient characteristics.
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Affiliation(s)
| | - Agnieszka Nowicka
- Chair and Department of Neonatology, Poznan University of Medical Sciences, Poznan, Poland
| | | | | | - Janusz Gadzinowski
- Chair and Department of Neonatology, Poznan University of Medical Sciences, Poznan, Poland
| | - Dawid Szpecht
- Chair and Department of Neonatology, Poznan University of Medical Sciences, Poznan, Poland
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NT-proBNP Concentrations in the Umbilical Cord and Serum of Term Neonates: A Systematic Review and Meta-Analysis. Diagnostics (Basel) 2022; 12:diagnostics12061416. [PMID: 35741227 PMCID: PMC9222102 DOI: 10.3390/diagnostics12061416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 05/29/2022] [Accepted: 06/06/2022] [Indexed: 11/16/2022] Open
Abstract
The detection of NT-proBNP levels both in umbilical cord blood (UCB) samples and in serum samples collected from healthy term neonates during the neonatal period. A systematic review of relevant literature in accordance with PRISMA guidelines was conducted. For quality appraisal, the potential risk of bias was assessed using the BIOCROSS evaluation tool. The random-effects and fixed-effects models were used to calculate weighted mean differences with a corresponding 95% confidence interval. A total of forty (40) studies met the inclusion criteria for the systematic review. After further examination, eighteen (18) studies (1738 participants) from the UCB sample group and fourteen (14) studies (393 participants) from the serum sample group were selected to perform a meta-analysis. Using the fixed-effects model, the mean intervals of NT-proBNP in UCB and serum samples were 492 pg/mL (95% CI: 480−503 pg/mL) and 1341 pg/mL (95% CI: 1286−1397 pg/mL), respectively. A higher concentration of ΝΤ-proBNP was observed in the serum sample group compared to the UCB samples (p < 0.001). We present the intervals of NT-proBNP in UCB and in the serum of healthy term neonates. The determination of the potential effect of perinatal factors on the biomarker’s reference range was also aimed.
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Abstract
Prematurity and other complications at birth are nutritional emergencies. Parenteral nutrition is a bridge to enteral nutrition for a few days or months, and sometimes the sole source of nutrition for life. Parenteral nutrition regimens are constructed to provide adequate and balanced energy, macronutrients, and micronutrients to support growth and prevent deficiencies. Neonatal parenteral nutrition regimens are complicated by periodic shortages of essential products, compatibility challenges, and contaminants. Newborns benefit from serial growth assessments, monitoring of biochemical status, nutrition-focused physical examinations, and management by a multidisciplinary team to ensure adequacy of parenteral nutrition and promote best outcomes.
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Affiliation(s)
- Sharon Groh-Wargo
- Nutrition and Pediatrics, Case Western Reserve University at MetroHealth Medical Center, 2500 MetroHealth Drive, C.G72, Cleveland, OH 44109-1998, USA
| | - Stephanie Merlino Barr
- Neonatal Dietitian, Department of Pediatrics, MetroHealth Medical Center, 2500 MetroHealth Drive, C.G72, Cleveland, OH 44109-1998, USA.
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Zozaya C, Aziz K, Singhal N, Ye XY, Drolet C, Emberley J, Lee KS, Shah VS. Association of Weight Changes by Three Days after Birth and Mortality and/or Severe Neurological Injury in Preterm Infants < 29 Weeks Gestational Age: A Multicenter Cohort Study. CHILDREN (BASEL, SWITZERLAND) 2022; 9:276. [PMID: 35204996 PMCID: PMC8870872 DOI: 10.3390/children9020276] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/13/2022] [Accepted: 02/13/2022] [Indexed: 11/16/2022]
Abstract
OBJECTIVE This study aimed to determine the range of weight loss, at 3 days postnatal age, associated with the lowest risk of mortality/short-term morbidity in preterm infants <29 weeks gestational age (GA). STUDY DESIGN This multicenter retrospective cohort study employed data from the Canadian Neonatal Network database. The primary outcome was a composite of mortality and/or severe neurological injury. Multivariable quadratic and linear regression models which adjusted for potential confounders were built. RESULTS A total of 9275 preterm infants (median GA 26, IQR 25, 28 weeks) were included. The optimal weight change range at day three, after adjustment for potential confounders for the primary outcomes, was -15 to -8.9%. CONCLUSIONS There is a 'U'-shaped relationship between weight change from birth to day three and mortality and/or severe neurological injury. Interventional studies, which target weight loss within the range found in this study and evaluate the impact on neonatal outcomes, are needed to corroborate our findings.
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Affiliation(s)
- Carlos Zozaya
- Department of Paediatrics, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada;
| | - Khalid Aziz
- Department of Pediatrics, University of Alberta, Edmonton, AB T6G 1C9, Canada;
| | - Nalini Singhal
- Department of Pediatrics, University of Calgary, Calgary, AB T2N 1N4, Canada;
| | - Xiang Y. Ye
- Maternal-Infant Care (MiCare) Research Centre, Mount Sinai Hospital, Toronto, ON M5G 1X6, Canada;
| | - Christine Drolet
- Centre Mère-Enfant Soleil, Centre Hospitalier Universitaire de Québec, Université Laval, Quebec City, QC G1V 4G2, Canada;
| | - Julie Emberley
- Department of Pediatrics, Janeway Children’s Health and Rehabilitation Center, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, Canada;
| | - Kyong-Soon Lee
- Division of Neonatology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada;
| | - Vibhuti S. Shah
- Department of Paediatrics, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada;
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Shafa A, Shatabi H, Moghadam N, Habibzade M. Comparison the effects of using two methods of fluid therapy with normal saline or 5% dextrose in half amount of normal saline solution on blood glucose and plasma electrolytes during and after neonatal surgeries: A randomized controlled trial. J Clin Neonatol 2022. [DOI: 10.4103/jcn.jcn_131_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Zanardo V, Tortora D, Parotto M, Severino L, Guerrini P, Straface G. Fluid status changes during the transition in infants of diabetic mothers. Eur J Pediatr 2022; 181:245-252. [PMID: 34268592 DOI: 10.1007/s00431-021-04197-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 06/16/2021] [Accepted: 07/06/2021] [Indexed: 10/20/2022]
Abstract
In animal and human neonates, expansion of the extracellular fluid volume is associated with "wet" lung and poor respiratory outcomes. To define fluid status changes during the transition from fetal to neonatal life in infants of diabetic mothers (IDM), we conducted a single-centre (Policlinico Abano Terme, Abano Terme, Italy) study of 66 IDM and a 1:2 matched control group from January 1 to September 30, 2020. Fluid status changes were assessed by computing Δ Hct from umbilical cord blood at birth and capillary heel Hct at 48 h, accounting for body weight decrease. IDM presented with significantly lower cord blood Hct levels in comparison to controls (47.33 ± 4.52 vs 50.03 ± 3.51%, p < 0.001), mainly if delivered by elective cesarean Sect. (45.01 ± 3.77 vs 48.43 ± 3.50%, p = 0.001). Hct levels at 48 h were comparable (55.18 ± 5.42 vs 54.62 ± 7.41%, p = 0.703), concurrently with similar body weight decrease (- 217.21 ± 113.34 vs - 217.51 ± 67.28 g, p = 0.614). This supports significantly higher ∆ Hct in IDM (5.13 ± 5.24 vs 7.29 ± 6.48, p < 0.01) and extra circulating fluid loss of 2-3%.Conclusion: Gestational diabetes is associated with an excess of circulating fluids during the transition from fetal to neonatal life, challenging the current assumption that is per se at risk of wet lung. What is Known: • In neonates, evidence suggests that expansion of the extracellular fluid volume prior to the postnatal diuresis is associated with poor respiratory outcomes. What is New: • Gestational diabetes is associated with an excess of circulating fluids during the transition from fetal to neonatal life, challenging the current assumption that is per se at risk of wet lung.
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Affiliation(s)
- Vincenzo Zanardo
- Division of Perinatal Medicine, Policlinico Abano Terme, Abano Terme, Italy.
| | | | - Matteo Parotto
- Institute of Anesthesiology, Toronto University, Toronto, Canada
| | - Lorenzo Severino
- Division of Perinatal Medicine, Policlinico Abano Terme, Abano Terme, Italy
| | - Pietro Guerrini
- Division of Perinatal Medicine, Policlinico Abano Terme, Abano Terme, Italy
| | - Gianluca Straface
- Division of Perinatal Medicine, Policlinico Abano Terme, Abano Terme, Italy
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14
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Individualized fluid management in extremely preterm neonates to ensure adequate diuresis without increasing complications. J Perinatol 2021; 41:240-246. [PMID: 32814823 DOI: 10.1038/s41372-020-00789-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 07/06/2020] [Accepted: 08/07/2020] [Indexed: 11/09/2022]
Abstract
OBJECTIVE Decrease the incidence of inadequate diuresis (ID, loss of <6% of birth weight) in extremely preterm neonates (EPT, <28 weeks of gestation at birth) during the first week of life by 50% in 1 year. STUDY DESIGN Quality improvement project in a level IV neonatal intensive care unit. A fluid management protocol was implemented, including the use of a fluid guide sheet and closer monitoring of hydration parameters. Seventy-nine baseline EPT neonates were compared to 83 post intervention. The incidence of ID was tracked monthly, along with prespecified morbidities and complications. Statistical data analyses also compared the pre- and post-intervention periods. RESULTS Fluid volumes in the first week were decreased (p < 0.001). ID decreased from 43 to 29% (p = 0.061). Tracked morbidities and complications were not statistically different. CONCLUSION Intentional and individualized adjustment of fluids led to decreased ID without increased hypernatremia and dehydration, or a change in tracked morbidities.
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15
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Langer T, D'Oria V, Spolidoro GCI, Chidini G, Scalia Catenacci S, Marchesi T, Guerrini M, Cislaghi A, Agostoni C, Pesenti A, Calderini E. Fluid therapy in mechanically ventilated critically ill children: the sodium, chloride and water burden of fluid creep. BMC Pediatr 2020; 20:424. [PMID: 32891127 PMCID: PMC7487923 DOI: 10.1186/s12887-020-02322-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 08/25/2020] [Indexed: 12/15/2022] Open
Abstract
Background Fluid therapy is a cornerstone of pediatric intensive care medicine. We aimed at quantifying the load of water, sodium and chloride due to different fluid indications in our pediatric intensive care unit (PICU). We were particularly interested in the role of fluid creep, i.e. fluid administered mainly as the vehicle for drugs, and the association between sodium load and water balance. Methods Critically ill children aged ≤3 years and invasively ventilated for ≥48 h between 2016 and 2019 in a single tertiary center PICU were retrospectively enrolled. Need for renal replacement therapy, plasmapheresis or parenteral nutrition constituted exclusion criteria. Quantity, quality and indication of fluids administered intravenously or enterally, urinary output and fluid balance were recorded for the first 48 h following intubation. Concentrations of sodium and chloride provided by the manufacturers were used to compute the electrolyte load. Results Forty-three patients (median 7 months (IQR 3–15)) were enrolled. Patients received 1004 ± 284 ml of water daily (153 ± 36 ml/kg/day), mainly due to enteral (39%), creep (34%) and maintenance (24%) fluids. Patients received 14.4 ± 4.8 mEq/kg/day of sodium and 13.6 ± 4.7 mEq/kg/day of chloride, respectively. The majority of sodium and chloride derived from fluid creep (56 and 58%). Daily fluid balance was 417 ± 221 ml (64 ± 30 ml/kg/day) and was associated with total sodium intake (r2 = 0.49, p < 0.001). Conclusions Critically ill children are exposed, especially in the acute phase, to extremely high loads of water, sodium and chloride, possibly contributing to edema development. Fluid creep is quantitatively the most relevant fluid in the PICU and future research efforts should address this topic in order to reduce the inadvertent water and electrolyte burden and improve the quality of care of critically ill children.
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Affiliation(s)
- Thomas Langer
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy. .,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Anestesia e Terapia Intensiva Donna-Bambino, Milan, Italy. .,Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
| | - Veronica D'Oria
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Anestesia e Terapia Intensiva Donna-Bambino, Milan, Italy
| | - Giulia C I Spolidoro
- Department of Clinical Sciences and Community Health, University of Milan, 20122, Milan, Italy
| | - Giovanna Chidini
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Anestesia e Terapia Intensiva Donna-Bambino, Milan, Italy
| | - Stefano Scalia Catenacci
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Anestesia e Terapia Intensiva Donna-Bambino, Milan, Italy
| | - Tiziana Marchesi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Anestesia e Terapia Intensiva Donna-Bambino, Milan, Italy
| | - Marta Guerrini
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Anestesia e Terapia Intensiva Donna-Bambino, Milan, Italy
| | - Andrea Cislaghi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Anestesia e Terapia Intensiva Donna-Bambino, Milan, Italy
| | - Carlo Agostoni
- Department of Clinical Sciences and Community Health, University of Milan, 20122, Milan, Italy.,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Pediatric Intermediate Care Unit, 20122, Milan, Italy
| | - Antonio Pesenti
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.,Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Edoardo Calderini
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Anestesia e Terapia Intensiva Donna-Bambino, Milan, Italy
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Eibensteiner F, Laml-Wallner G, Thanhaeuser M, Ristl R, Ely S, Jilma B, Berger A, Haiden N. ELBW infants receive inadvertent sodium load above the recommended intake. Pediatr Res 2020; 88:412-420. [PMID: 32272484 DOI: 10.1038/s41390-020-0867-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2019] [Revised: 02/27/2020] [Accepted: 03/04/2020] [Indexed: 11/09/2022]
Abstract
BACKGROUND To determine total sodium load, including inadvertent load, during the first 2 postnatal weeks, and its influence on serum sodium, morbidity, and mortality in extremely low birth weight (ELBW, birth weight <1000 g) infants and to calculate sodium replacement models. METHODS Retrospective data analysis on ELBW infants with a gestational age <28 + 0/7 weeks. RESULTS Ninety patients with a median birth weight of 718 g and a median gestational age of 24 + 6/7 weeks were included. Median sodium intake during the first 2 postnatal weeks was 10.2 mmol/kg/day, which was significantly higher than recommended (2-5 mmol/kg/day). Sodium intake did not affect the risk for hypernatremia. Each mmol of sodium intake during the first postnatal week was associated with an increased risk of bronchopulmonary dysplasia (45%) and higher-grade intraventricular hemorrhage (31%), during the second postnatal week for necrotizing enterocolitis (19%), and during both postnatal weeks of mortality (13%). Calculations of two sodium replacement models resulted in a decrease in sodium intake during the first postnatal week of 3.2 and 4.0 mmol/kg/day, respectively. CONCLUSIONS Sodium load during the first 2 postnatal weeks of ELBW infants was significantly higher than recommended owing to inadvertent sodium intake and was associated with a higher risk of subsequent morbidity and mortality, although the study design does not allow conclusions on causality. Replacement of 0.9% saline with alternative carrier solutions might reduce sodium intake. IMPACT Sodium intake in ELBW infants during the first 2 postnatal weeks was twofold to threefold higher than recommended; this was mainly caused by inadvertent sodium components. High sodium intake is not related to severe hypernatremia but might be associated with a higher morbidity in terms of BPD, IVH, and NEC. Inadvertent sodium load can be reduced by replacing high sodium-containing carrier solutions with high levels of sodium with alternative hypotonic and/or balanced fluids, model based.
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Affiliation(s)
- Fabian Eibensteiner
- Department of Paediatrics, Division of Neonatology, Paediatric Intensice Care and Neuropaediatrics, Medical University of Vienna, Vienna, Austria
| | - Gerda Laml-Wallner
- Drug Information and Clinical Pharmacy Services, Pharmacy Department, General Hospital of the City of Vienna-Hospital of the Medical University of Vienna, Vienna, Austria
| | - Margarita Thanhaeuser
- Department of Paediatrics, Division of Neonatology, Paediatric Intensice Care and Neuropaediatrics, Medical University of Vienna, Vienna, Austria
| | - Robin Ristl
- Center of Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria
| | - Sarah Ely
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Bernd Jilma
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Angelika Berger
- Department of Paediatrics, Division of Neonatology, Paediatric Intensice Care and Neuropaediatrics, Medical University of Vienna, Vienna, Austria
| | - Nadja Haiden
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
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Tuzun F, Akcura Y, Duman N, Ozkan H. Comparison of isotonic and hypotonic intravenous fluids in term newborns: is it time to quit hypotonic fluids. J Matern Fetal Neonatal Med 2020; 35:356-361. [PMID: 32223482 DOI: 10.1080/14767058.2020.1718094] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Objective: Hypotonic fluids have been traditionally used in newborns. National Institute for Health and Clinical Excellence-2015 (NICE) fluid therapy guideline recommends the use of isotonic fluids as maintenance fluid therapy in term newborns. However, there is no clear evidence supporting this recommendation. This study aims to compare isotonic (5% dextrose in 0.9% sodium chloride (NaCl)) and hypotonic (5% dextrose in 0.45% NaCl) parenteral fluid therapies in hospitalized term newborns with regard to changes in plasma Na (pNa) and complications related with fluid therapy.Methods: This was a retrospective cohort study performed in a tertiary university hospital NICU between January 2016 and April 2018. Term newborns who were initially isonatremic or mildly dysnatremic (pNa <130 or >155 meq/L) and receiving fluid therapy for maintenance or replacement therapy after 48th postnatal hours were eligible for the study. Infants having specific diagnoses requiring extraordinary fluids were excluded. The primary outcome evaluated was the change in mean plasma Na (ΔpNa meq/L/h) at 24 h or at the end of intravenous (i.v.) fluid therapy. Secondary outcomes evaluated were the risk of hyponatremia, hypernatremia, and adverse events attributable to fluid administration.Results: Among the 108 included newborns, 57 received hypotonic fluid (5% dextrose solution in 0.45% NaCl) and the remaining received isotonic fluid (5% dextrose solution in 0.9% NaCl) therapy. The hypotonic fluid group showed a greater ΔpNa compared to the isotonic group (0.48 ± 0.28 vs. 0.27 ± 0.21 meq/L/h, p = .001). The risk of experiencing unsafe plasma Na decrease in the hypotonic fluid group (ΔpNa >0.5 meq/L/h) was higher than the isotonic fluid group (odd ratio: 8.46; 95% confidence interval (CI): 2.3-30.06). Six mildly hypernatremic babies between 48 and 72 h of postnatal age showed insufficient Na reduction despite the appropriate amount of fluid. No significant difference was found between the two groups in terms of other outcomes.Conclusion: The results of this study suggested that as maintenance or replacement fluid therapy in the newborn, hypotonic fluids, even 5% dextrose in 0.45% NaCl, can lead to unsafe plasma Na decreases in term newborns, while isotonic fluids are safe when started after the first few days of life. Although the results parallel NICE guidelines, before making recommendations regarding the removal of hypotonic fluids entirely from clinical practice in term newborns following the renal adaptation period; larger randomized controlled studies involving a wide range of babies are needed.
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Affiliation(s)
- Funda Tuzun
- Department of Pediatrics, Division of Neonatology, Dokuz Eylül University Faculty of Medicine, Izmir, Turkey
| | - Yagmur Akcura
- Department of Pediatrics, Division of Neonatology, Dokuz Eylül University Faculty of Medicine, Izmir, Turkey
| | - Nuray Duman
- Department of Pediatrics, Division of Neonatology, Dokuz Eylül University Faculty of Medicine, Izmir, Turkey
| | - Hasan Ozkan
- Department of Pediatrics, Division of Neonatology, Dokuz Eylül University Faculty of Medicine, Izmir, Turkey
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18
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Lehr AR, Rached-d’Astous S, Parker M, McIntyre L, Sampson M, Hamid J, Menon K. Impact of balanced versus unbalanced fluid resuscitation on clinical outcomes in critically ill children: protocol for a systematic review and meta-analysis. Syst Rev 2019; 8:195. [PMID: 31383009 PMCID: PMC6683512 DOI: 10.1186/s13643-019-1109-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 07/22/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Isotonic crystalloid fluid bolus therapy is used in critically ill children to restore or maintain hemodynamic stability. However, the ideal choice of crystalloid remains to be determined. The most easily available and most frequently used crystalloid is 0.9% saline, an unbalanced crystalloid, that has been associated with hyperchloremic metabolic acidosis and acute kidney injury (AKI). Balanced fluids such as Ringer's lactate (RL) were developed to be closer to the composition of serum. However, they are more expensive and less readily available than 0.9% saline. Few trials have found RL to be associated with more favorable outcomes, but pediatric data is limited and inconsistent. The objective of the present systematic review is to review existing literature to determine the effect of balanced versus unbalanced fluid bolus therapy on metabolic acidosis in critically ill children. METHODS Using the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines, we will conduct a systematic review to retrieve all controlled trials and observational studies comparing balanced and unbalanced resuscitative fluids in critically ill children from age 28 days to 18 years old in any resuscitation settings. Search strategy was developed in collaboration with an experienced clinical research librarian. The primary outcome is the incidence and/or time to resolution of metabolic acidosis. Secondary outcomes included the incidence of hyperchloremia, AKI, duration of renal replacement therapy, vasopressors, mechanical ventilation, total volume of rehydration needed per day, extracorporeal membrane oxygenation, and length of stay and mortality. Study screening, inclusion, data extraction, and assessment of risk of bias will be performed independently by two authors. We intend to perform a meta-analysis with studies that are compatible on the basis of population and outcomes. DISCUSSION Isotonic crystalloid fluid bolus therapy is a ubiquitous treatment in resuscitation of critically ill pediatric patients and yet there is no clear recommendation to support the choice of balanced versus unbalanced fluid. The present review will summarize current available data in the literature and assess whether recommendations can be generated regarding the choice of crystalloids or otherwise identify knowledge gaps which will open the door to a large-scale randomized controlled trial (RCT).
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Affiliation(s)
- Anab Rebecca Lehr
- Division of Critical Care, Department of Pediatrics, University of Ottawa, Children’s Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON K1H 8L1 Canada
| | - Soha Rached-d’Astous
- Division of Emergency Medicine, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, ON Canada
| | - Melissa Parker
- Division of Emergency Medicine, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, ON Canada
- Division of Critical Care, Department of Pediatrics, McMaster University, Hamilton, ON Canada
| | - Lauralyn McIntyre
- Division of Critical Care, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON Canada
| | - Margaret Sampson
- Library Services, Children’s Hospital of Eastern Ontario, Ottawa, ON Canada
| | - Jemila Hamid
- Clinical Research Unit, Children’s Hospital of Eastern Ontario, Ottawa, ON Canada
| | - Kusum Menon
- Division of Critical Care, Department of Pediatrics, University of Ottawa, Children’s Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON K1H 8L1 Canada
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19
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Johnson SC, Pan A, Sun GX, Freed A, Stokes JC, Bornstein R, Witkowski M, Li L, Ford JM, Howard CRA, Sedensky MM, Morgan PG. Relevance of experimental paradigms of anesthesia induced neurotoxicity in the mouse. PLoS One 2019; 14:e0213543. [PMID: 30897103 PMCID: PMC6428290 DOI: 10.1371/journal.pone.0213543] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 02/24/2019] [Indexed: 11/30/2022] Open
Abstract
Routine general anesthesia is considered to be safe in healthy individuals. However, pre-clinical studies in mice, rats, and monkeys have repeatedly demonstrated that exposure to anesthetic agents during early post-natal periods can lead to acute neurotoxicity. More concerning, later-life defects in cognition, assessed by behavioral assays for learning and memory, have been reported. Although the potential for anesthetics to damage the neonatal brain is well-documented, the clinical significance of the pre-clinical models in which damage is induced remains quite unclear. Here, we systematically evaluate critical physiological parameters in post-natal day 7 neonatal mice exposed to 1.5% isoflurane for 2–4 hours, the most common anesthesia induced neurotoxicity paradigm in this animal model. We find that 2 or more hours of anesthesia exposure results in dramatic respiratory and metabolic changes that may limit interpretation of this paradigm to the clinical situation. Our data indicate that neonatal mouse models of AIN are not necessarily appropriate representations of human exposures.
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Affiliation(s)
- Simon C. Johnson
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States of America
- Department of Neurology, University of Washington, Seattle, WA, United States of America
- * E-mail:
| | - Amanda Pan
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States of America
| | - Grace X. Sun
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States of America
| | - Arielle Freed
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States of America
- University of Washington School of Dentistry, Seattle, WA, United States of America
| | - Julia C. Stokes
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States of America
| | - Rebecca Bornstein
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States of America
- Department of Pathology, University of Washington, Seattle, WA, United States of America
| | - Michael Witkowski
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States of America
| | - Li Li
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States of America
| | - Jeremy M. Ford
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States of America
- Seattle Children's Imagination Lab, Seattle Children’s Research Institute, Seattle, WA, United States of America
| | - Christopher R. A. Howard
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States of America
- Seattle Children's Imagination Lab, Seattle Children’s Research Institute, Seattle, WA, United States of America
| | - Margaret M. Sedensky
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States of America
- Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States of America
| | - Philip G. Morgan
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States of America
- Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States of America
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20
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Arumainathan R, Stendall C, Visram A. Management of fluids in neonatal surgery. BJA Educ 2018; 18:199-203. [PMID: 33456833 DOI: 10.1016/j.bjae.2018.03.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/14/2018] [Indexed: 10/16/2022] Open
Affiliation(s)
| | - C Stendall
- Great Ormond Street Hospital, London, UK
| | - A Visram
- Royal London Hospital, London, UK
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21
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Burn Shock and Resuscitation: Proceedings of a Symposium Conducted at the Meeting of the American Burn Association, Chicago, IL, 21 April 2015. J Burn Care Res 2018; 38:e423-e431. [PMID: 28009701 DOI: 10.1097/bcr.0000000000000417] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The Special Interest Groups of the American Burn Association provide a forum for interested members of the multidisciplinary burn team to congregate and discuss matters of mutual interest. At the 47th Annual Meeting of the American Burn Association in Chicago, IL, the Fluid Resuscitation Special Interest Group sponsored a special symposium on burn resuscitation. The purpose of the symposium was to review the history, current status, and future direction of fluid resuscitation of patients with burn shock. The reader will note several themes running through the following presentations. One is the perennial question of the proper role for albumin or other fluid-sparing strategies. Another is the unique characteristics of the pediatric burn patient. A third is the need for multicenter trials of burn resuscitation, while recognizing the obstacles to conducting randomized controlled trials in this setting.
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22
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Tuplin MC, Romero AE, Boysen SR. Influence of the Respiratory Cycle on Caudal Vena Cava Diameter Measured by Sonography in Healthy Foals: A Pilot Study. J Vet Intern Med 2017; 31:1556-1562. [PMID: 28766820 PMCID: PMC5598903 DOI: 10.1111/jvim.14793] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 05/04/2017] [Accepted: 06/22/2017] [Indexed: 11/27/2022] Open
Abstract
Background Intravascular volume assessment in foals is challenging. In humans, intravascular volume status is estimated by the caudal vena cava (CVC) collapsibility index (CVC‐CI) defined as (CVC diameter at maximum expiration [CVCmax] – CVC diameter at minimal inspiration [CVCmin])/CVCmax × 100%. Hypothesis/Objectives To determine whether the CVC could be sonographically measured in healthy foals, determine differences in CVCmax and CVCmin, and calculate inter‐ and intrarater variability between 2 examiners. We hypothesized that the CVC could be measured sonographically at the subxiphoid view and that there would be a difference between CVCmax and CVCmin values. Animals Sixty privately owned foals <1‐month‐old. Methods Prospective study. A longitudinal subxiphoid sonographic window in standing foals was used. The CVCmax and CVCmin were analyzed by a linear mixed effect model. Inter‐rater agreement and intrarater variability were expressed by Bland‐Altman and intraclass correlation coefficients, respectively. Results Measurements were attained from 58 of 60 foals with mean age of 15 ± 7.9 days and mean weight of 75.7 ± 17.7 kg. The CVCmax was significantly different from CVCmin (D = 0.515, SE = 0.031, P < 0.001). Inter‐rater agreement of the CVC‐CI differed by an average of −0.9% (95% limits of agreement, −12.5 to +10.7%). Intrarater variability of CVCmax was 0.540 and 0.545, of CVCmin was 0.550 and 0.594, and of CVC‐CI was 0.894 and 0.853 for observers 1 and 2, respectively. Conclusions and Clinical Importance These results indicate it is possible to reliably measure the CVC sonographically in healthy foals, and the CVC‐CI may prove useful in assessing the intravascular volume status in hypovolemic foals.
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Affiliation(s)
- M C Tuplin
- Department of Veterinary Clinical and Diagnostic Sciences, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada
| | - A E Romero
- Department of Veterinary Clinical and Diagnostic Sciences, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada
| | - S R Boysen
- Department of Veterinary Clinical and Diagnostic Sciences, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada
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Sundaram A, Alshaikh B, Dersch-Mills D, Dobry J, Akierman AR, Yusuf K. Extended-interval Dosing of Gentamicin in Premature Neonates Born at <32 Weeks' Gestation and >7 Days of age. Clin Ther 2017; 39:1233-1241. [PMID: 28579209 DOI: 10.1016/j.clinthera.2017.05.343] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2017] [Revised: 05/10/2017] [Accepted: 05/10/2017] [Indexed: 11/27/2022]
Abstract
PURPOSE Extended-interval dosing (EID) regimens of gentamicin have been validated for treating confirmed or suspected early- and late-onset sepsis in preterm infants in the first week of life. Despite the marked changes in volume of distribution and renal clearance in preterm infants after the first few days of life, few studies have validated EID regimens of gentamicin in this population. The objective of the study was to evaluate an EID regimen of gentamicin in infants born at <32 weeks' gestational age and aged >7 days. METHODS This observational study of an EID regimen was conducted in 39 infants. Dosing interval was based on the serum drug concentration at 22 hours after the administration of the first dose of 5 mg/kg. Gentamicin peak (5-12 µg/mL) and trough (<2 µg/mL) levels were compared to those in a historical control group of 39 infants who received traditional-interval dosing (TID) of 2.5 mg/kg of gentamicin with dosing intervals of 8, 12, or 24 hours. FINDINGS There were no differences in birthweight, gestational age at birth, postmenstrual age, weight at the start of gentamicin administration, postnatal age, small for gestational age status, antenatal corticosteroid use, or postnatal indomethacin exposure between the 2 groups. In the EID group, dosing intervals were 24 hours in 30 infants, 36 hours in 6 infants, and 48 hours in 3 infants. Compared with the TID group (n = 39), the EID group had a significantly higher peak level (median, 9.0 vs 4.7 µg/mL) and a significantly lower trough level (median, 0.7 vs 1.1 µg/mL) (both, P < 0.001). On regression analysis, the postmenstrual age was correlated significantly with trough levels in the EID group. There was no adverse effect on renal function in either group. On follow-up, 1 infant in the EID group and 2 infants in the TID group had evidence of sensorineural hearing loss. IMPLICATIONS In infants born at <32 weeks' gestation and >7 days of age, an EID gentamicin regimen, with a dosing interval based on a single concentration measurement at 22 hours after the administration of the first dose, achieved therapeutic peak and trough levels and performed significantly better than did a TID regimen in reaching target peak and trough levels. Larger-scale trials are needed for assessing the clinical efficacy (treatment failure/success) of these regimens.
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Affiliation(s)
- Arun Sundaram
- Section of Neonatology, Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Belal Alshaikh
- Section of Neonatology, Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | | | - Jenna Dobry
- Section of Neonatology, Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Albert R Akierman
- Section of Neonatology, Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Kamran Yusuf
- Section of Neonatology, Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
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Li G, Standing JF, Bielicki J, Hope W, van den Anker J, Heath PT, Sharland M. The Potential Role of Fosfomycin in Neonatal Sepsis Caused by Multidrug-Resistant Bacteria. Drugs 2017; 77:941-950. [PMID: 28456943 DOI: 10.1007/s40265-017-0745-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
The broad-spectrum activity of fosfomycin, including against multidrug-resistant (MDR) strains, has led to renewed interest in its use in recent years. Neonatal sepsis remains a substantial cause of morbidity and mortality at a global level, with evidence that MDR bacteria play an increasing role. The evidence for use of fosfomycin in neonatal subjects is limited. We summarise current knowledge of the pharmacokinetics and clinical outcomes for the use of fosfomycin in neonatal sepsis and issues specific to neonatal physiology. While fosfomycin has a broad range of coverage, we evaluate the extent to which it may be effective against MDR bacteria in a neonatal setting, in light of recent evidence suggesting it to be most effective when administered in combination with other antibiotics. Given the urgency of clinical demand for treatment of MDR bacterial sepsis, we outline directions for further work, including the need for future clinical trials in this at-risk population.
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Affiliation(s)
- Grace Li
- Paediatric Infectious Diseases Research Group, Institute of Infection and Immunity, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK
| | - Joseph F Standing
- Paediatric Infectious Diseases Research Group, Institute of Infection and Immunity, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.,UCL Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK
| | - Julia Bielicki
- Paediatric Infectious Diseases Research Group, Institute of Infection and Immunity, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.,Division of Paediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital (UKBB), Spitalstrasse 33, Postfach, 4031, Basel, Switzerland
| | - William Hope
- Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, University of Liverpool, Sherrington Building, Liverpool, L69 3GE, UK
| | - John van den Anker
- Division of Paediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital (UKBB), Spitalstrasse 33, Postfach, 4031, Basel, Switzerland.,Division of Clinical Pharmacology, Children's National Health System, Washington, DC, USA
| | - Paul T Heath
- Paediatric Infectious Diseases Research Group, Institute of Infection and Immunity, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK
| | - Mike Sharland
- Paediatric Infectious Diseases Research Group, Institute of Infection and Immunity, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.
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Abstract
It is widely accepted that sodium is an essential nutritional electrolyte and its deficiency is associated with neurological sequelae and poor growth. The provision of an adequate sodium intake to preterm neonates is hampered by the technical difficulty in clinically assessing total body sodium content. As addressed in this review, there is a lack of consensus on the definition of hyponatremia early in life, but there is no evidence that it should deviate from the widely accepted normative data for adult subjects. A low urinary sodium content is accepted by many as reflecting total body sodium deficiency, yet spot urinary sodium measurements are of questionable clinical value. The hormonal regulation of sodium homeostasis is here reviewed and the mechanism accounting for sodium deficiency-induced growth impairment in preterm infants addressed. Lastly, we provide evidence-based gestational and postnatal age-dependent recommendations for the provision of adequate sodium intake to preterm neonates.
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Bhayat SI, Gowda HMS, Eisenhut M. Should dopamine be the first line inotrope in the treatment of neonatal hypotension? Review of the evidence. World J Clin Pediatr 2016; 5:212-222. [PMID: 27170932 PMCID: PMC4857235 DOI: 10.5409/wjcp.v5.i2.212] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 12/17/2015] [Accepted: 01/19/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine if dopamine is effective in treating neonatal hypotension and safe to use comparing to other inotropes.
METHODS: This is a review of evidence on inotropic treatment of neonatal hypotension. Databases searched were MEDLINE and the Cochrane Library, a total of 134 studies were identified. Only studies with high quality evidence (level 1a and b and 2a) were included. After review, only eight studies were included in the final analysis. Pooled risk ratios derived for each outcome [Mantel-Haenzel (M-H) fixed effect] with CI, as reported in the Cochrane reviews were plotted in forest plot form.
RESULTS: Eight articles met inclusion criteria, which all included treatment in preterm infants. Dopamine increased mean arterial blood pressure (BP) (n = 163; r = 0.88, 95%CI: 0.76 to 0.94) and systolic BP (n = 142; r = 0.81, 95%CI: 0.42 to 0.94) comparing to placebo. Dopamine has been shown overall to be statistically more effective in increasing BP than dobutamine (n = 251, r = 0.26, 95%CI: 0.20-0.32). However there were no differences in short term outcomes (periventricular leucomalacia, periventricular haemorrhage) and mortality between both drugs. There is no statistical evidence of dopamine being more effective than adrenaline or corticosteroids. There was no difference in morbidity and mortality outcomes when dopamine was compared to hydrocortisone (RR 1.81, 95%CI: 0.18 to 18.39) or adrenaline.
CONCLUSION: In preterms, dopamine is the most studied drug, and we suggest it could be used as first line treatment in hypotension.
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Visram AR. Intraoperative fluid therapy in neonates. SOUTHERN AFRICAN JOURNAL OF ANAESTHESIA AND ANALGESIA 2016. [DOI: 10.1080/22201181.2016.1140705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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