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  • Systematic Review
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Assessment of hemodynamic dysfunction in septic newborns by functional echocardiography: a systematic review

Pediatric Research (2024)Cite this article

Abstract

Background

Neonatal sepsis remains a leading cause of mortality in neonatal units. Neonatologist-performed echocardiography (NPE) offers the potential for early detection of sepsis-associated cardiovascular dysfunction. This review examines available echocardiographic findings in septic neonates.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed prospective observational, cross-sectional, case control, and cohort studies on septic newborns with echocardiographic assessments from PubMed, Scopus and Embase. Quality assessment employed the Newcastle–Ottawa Scale, with results analyzed descriptively.

Results

From an initial pool of 1663 papers, 12 studies met inclusion criteria after relevance screening and eliminating duplicates/excluded studies. The review encompassed 438 septic newborns and 232 controls. Septic neonates exhibited either increased risk of pulmonary hypertension or left ventricular diastolic dysfunction, and a warm shock physiology characterized by higher cardiac outputs.

Discussion

The included studies exhibited heterogeneity in sepsis definitions, sepsis severity scores, echocardiographic evaluations, and demographic data of newborns. Limited sample sizes compromised analytical interpretability. Nonetheless, this work establishes a foundation for future high-quality echocardiographic studies.

Conclusion

Our review confirms that septic neonates show significant hemodynamic changes that can be identified using NPE. These findings underscore the need for wider NPE use to tailor hemodynamics-based strategies within this population.

Impact

  1. 1.

    Our study emphasizes the value of neonatologist-performed echocardiography (NPE) as a feasible tool for identifying significant hemodynamic changes in septic neonates.

  2. 2.

    Our study underscores the importance of standardized echocardiographic protocols and frequent monitoring of cardiac function in septic neonates.

  3. 3.

    The impact of the study lies in its potential to increase researchers’ awareness for the need for more high-quality echocardiographic data in future studies. By promoting wider use of NPE, neonatologists can more accurately assess the hemodynamic status of septic newborns and tailor treatment approaches, potentially improving patient outcomes.

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Fig. 1: Traditionally used echocardiographic views in neonatologist-performed echocardiography.
Fig. 2: PRISMA flow diagram of study selection.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Jacob, J., Kamitsuka, M., Clark, R. H., Kelleher, A. S. & Spitzer, A. R. Etiologies of NICU deaths. Pediatrics 135, e59–e65 (2015).

    Article  PubMed  Google Scholar 

  2. Raj, S., Killinger, J. S., Gonzalez, J. A. & Lopez, L. Myocardial dysfunction in pediatric septic shock. J. Pediatr. 164, 72–77.e2 (2014).

    Article  PubMed  Google Scholar 

  3. Weiss, S. L. et al. The epidemiology of hospital death following pediatric severe sepsis: when, why, and how children with sepsis die*. Pediatr. Crit. Care Med. 18, 823–830 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Schmatz, M. et al. Surviving sepsis in a referral neonatal intensive care unit: association between time to antibiotic administration and in-hospital outcomes. J. Pediatr. 217, 59–65.e1 (2020).

    Article  PubMed  Google Scholar 

  5. Kharrat, A. & Jain, A. Hemodynamic dysfunction in neonatal sepsis. Pediatr. Res. 91, 413–424 (2022).

    Article  PubMed  Google Scholar 

  6. Ince, C. et al. The endothelium in sepsis. Shock 45, 259–270 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Knuefermann, P. et al. Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of Toll-like receptor 9. Cardiovasc. Res. 78, 26–35 (2008).

    Article  CAS  PubMed  Google Scholar 

  8. Virág, M., Leiner, T., Rottler, M., Ocskay, K. & Molnar, Z. Individualized hemodynamic management in sepsis. J. Pers. Med. 11, 157 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Cuenca, J., Martín-Sanz, P., Álvarez-Barrientos, A. M., Boscá, L. & Goren, N. Infiltration of inflammatory cells plays an important role in matrix metalloproteinase expression and activation in the heart during sepsis. Am. J. Pathol. 169, 1567–1576 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Frayn, K. N. Hormonal control of metabolism in trauma and sepsis. Clin. Endocrinol. 24, 577–599 (1986).

    Article  CAS  Google Scholar 

  11. Aradhya, A. S. et al. Low vasopressin and progression of neonatal sepsis to septic shock: a prospective cohort study. Eur. J. Pediatr. 179, 1147–1155 (2020).

    Article  CAS  PubMed  Google Scholar 

  12. Khashana, A., Ojaniemi, M., Leskinen, M., Saarela, T. & Hallman, M. Term neonates with infection and shock display high cortisol precursors despite low levels of normal cortisol. Acta Paediatr. 105, 154–158 (2016).

    Article  CAS  PubMed  Google Scholar 

  13. Ni, M. et al. Use of vasopressin in neonatal intensive care unit patients with hypotension. J. Pediatr. Pharmacol. Ther. 22, 430–435 (2017).

    PubMed  PubMed Central  Google Scholar 

  14. LeFlore, J. L. & Engle, W. D. Capillary refill time is an unreliable indicator of cardiovascular status in term neonates. Adv. Neonatal Care 5, 147–154 (2005).

    Article  PubMed  Google Scholar 

  15. Takci, S., Yigit, S., Korkmaz, A. & Yurdakök, M. Comparison between oscillometric and invasive blood pressure measurements in critically ill premature infants. Acta Paediatr. 101, 132–135 (2012).

    Article  PubMed  Google Scholar 

  16. Zonnenberg, I. A., van Dijk, J., van den Dungen, F. A. M., Vermeulen, R. J. & van Weissenbruch, M. M. The prognostic value of NIRS in preterm infants with (suspected) late-onset sepsis in relation to long term outcome: a pilot study. PLoS ONE 14, e0220044 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. de Boode, W. P. et al. The role of Neonatologist Performed Echocardiography in the assessment and management of neonatal shock. Pediatr. Res. 84, 57–67 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Groves, A. M. et al. Introduction to neonatologist-performed echocardiography. Pediatr. Res. 84, 1–12 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lai, W. W. et al. Guidelines and standards for performance of a pediatric echocardiogram: a report from the Task Force of the Pediatric Council of the American Society of Echocardiography. J. Am. Soc. Echocardiogr. 19, 1413–1430 (2006).

    Article  PubMed  Google Scholar 

  20. Mertens, L. et al. Targeted neonatal echocardiography in the neonatal intensive care unit: practice guidelines and recommendations for trainingwriting group of the American Society of Echocardiography (ASE) in collaboration with the European Association of Echocardiography (EAE) and the Association for European Pediatric Cardiologists (AEPC). J. Am. Soc. Echocardiogr. 24, 1057–1058 (2011).

    Article  PubMed  Google Scholar 

  21. Lopez, L. et al. Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J. Am. Soc. Echocardiogr. 23, 465–495 (2010).

    Article  PubMed  Google Scholar 

  22. Riggs, T. W. et al. Doppler echocardiographic evaluation of right and left ventricular diastolic function in normal neonates. J. Am. Collage Cardiol. 13, 700–705 (1989).

    Article  CAS  Google Scholar 

  23. Koestenberger, M. et al. Systolic right ventricular function in preterm and term neonates: reference values of the tricuspid annular plane systolic excursion (TAPSE) in 258 patients and calculation of Z-score values. Neonatology 100, 85–92 (2011).

    Article  PubMed  Google Scholar 

  24. Koestenberger, M. et al. Right ventricular function in infants, children and adolescents: reference values of the tricuspid annular plane systolic excursion (TAPSE) in 640 healthy patients and calculation of z score values. J. Am. Soc. Echocardiogr. 22, 715–719 (2009).

    Article  PubMed  Google Scholar 

  25. Aslan, E. et al. Left and right ventricular function by echocardiography, tissue Doppler imaging, carotid intima-media thickness, and asymmetric dimethyl arginine levels in obese adolescents with metabolic syndrome. Cardiol. Young 29, 310–318 (2019).

    Article  PubMed  Google Scholar 

  26. Basu, S. et al. Two-dimensional speckle tracking imaging detects impaired myocardial performance in children with septic shock, not recognized by conventional echocardiography*. Pediatr. Crit. Care Med. 13, 259–264 (2012).

    Article  PubMed  Google Scholar 

  27. Patel, M. D. et al. Cardiac dysfunction identified by strain echocardiography is associated with illness severity in pediatric sepsis. Pediatr. Crit. Care Med. 21, e192–e199 (2020).

    Article  PubMed  Google Scholar 

  28. Sanfilippo, F. et al. Echocardiographic parameters and mortality in pediatric sepsis: a systematic review and meta-analysis*. Pediatr. Crit. Care Med. 22, 251–261 (2021).

    Article  PubMed  Google Scholar 

  29. Sanfilippo, F. et al. Tissue Doppler assessment of diastolic function and relationship with mortality in critically ill septic patients: a systematic review and meta-analysis. Br. J. Anaesth. 119, 583–594 (2017).

    Article  CAS  PubMed  Google Scholar 

  30. Sanfilippo, F. et al. Diastolic dysfunction and mortality in septic patients: a systematic review and meta-analysis. Intensive Care Med. 41, 1004–1013 (2015).

    Article  PubMed  Google Scholar 

  31. Moher, D., Liberati, A., Tetzlaff, J. & Altman, D. G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 6, e1000097 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ottawa Hospital Research Institute. https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (2021).

  33. Abdel-Hady, H. E., Matter, M. K. & El-Arman, M. M. Myocardial dysfunction in neonatal sepsis: a tissue Doppler imaging study*. Pediatr. Crit. Care Med. 13, 318–323 (2012).

    Article  PubMed  Google Scholar 

  34. Ahmed, T., Abqari, S., Firdaus, U., Shahab, T. & Ali, S. M. Status of pulmonary artery pressures on echocardiography among high‑risk newborns. J. Clin. Neonatol. 9, 235–241 (2020).

    Article  Google Scholar 

  35. Alzahrani, A. K. Cardiac function affection in infants with neonatal sepsis. J. Clin. Trial 7, 5 (2017).

    Article  Google Scholar 

  36. Deshpande, S., Suryawanshi, P., Chaudhary, N. & Maheshwari, R. Cardiac output in late onset neonatal sepsis. J. Clin. Diagn. Res. 11, 4 (2017).

    Google Scholar 

  37. Deshpande, S. et al. Pulmonary hypertension in late onset neonatal sepsis using functional echocardiography: a prospective study. J. Ultrasound 25, 233–239 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Fahmey, S. S., Hodeib, M., Refaat, K. & Mohammed, W. Evaluation of myocardial function in neonatal sepsis using tissue Doppler imaging. J. Matern. Fetal Neonatal Med. 33, 3752–3756 (2020).

    Article  PubMed  Google Scholar 

  39. Saini, S. S., Kumar, P. & Kumar, R. M. Hemodynamic changes in preterm neonates with septic shock: a prospective observational study*. Pediatr. Crit. Care Med. 15, 443–450 (2014).

    Article  PubMed  Google Scholar 

  40. Yengkhom, R. et al. Point of care neonatal ultrasound in late-onset neonatal sepsis. J. Neonatol. 35, 59–63 (2021).

    Article  Google Scholar 

  41. de Waal, K. & Evans, N. Hemodynamics in preterm infants with late-onset sepsis. J. Pediatr. 156, 918–922.e1 (2010).

    Article  PubMed  Google Scholar 

  42. Bandyopadhyay, T., Saili, A., Yadav, D. K. & Kumar, A. Correlation of functional echocardiography and clinical parameters in term neonates with shock. J. Neonatal Perinat. Med. 13, 167–173 (2020).

    Article  CAS  Google Scholar 

  43. Hassan, M. et al. PO-0540 changes in haemodynamic and peripheral perfusion in suspected neonatal sepsis. Arch. Dis. Child. 99, A426.2–A426 (2014).

    Article  Google Scholar 

  44. Tomerak, R. H., El-Badawy, A. A., Hussein, G., Kamel, N. R. M. & Razak, A. R. A. Echocardiogram done early in neonatal sepsis: what does it add? J. Investig. Med. 60, 680–684 (2012).

    Article  PubMed  Google Scholar 

  45. Töllner, U. Early diagnosis of septicemia in the newborn. Clinical studies and sepsis score. Eur. J. Pediatr. 138, 331–337 (1982).

    Article  PubMed  Google Scholar 

  46. Rodwell, R. L., Leslie, A. L. & Tudehope, D. I. Early diagnosis of neonatal sepsis using a hematologic scoring system. J. Pediatr. 112, 761–767 (1988).

    Article  CAS  PubMed  Google Scholar 

  47. NNF Teaching Aids. Newborn care. Neonatal sepsis. Management of neonatal sepsis. NNF clinical practice guidelines http://www.nnfi.org/assests/upload/usefull-links-pdf/Diagnosis_and_Management_of_Neonatal_Sepsis_NNFI_CPG_Dec2021.pdf (2021).

  48. Goldstein, B., Giroir, B. & Randolph, A., International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics*. Pediatr. Crit. Care Med. 6, 2–8 (2005).

    Article  PubMed  Google Scholar 

  49. de Boode, W. P. et al. Application of Neonatologist Performed Echocardiography in the assessment and management of persistent pulmonary hypertension of the newborn. Pediatr. Res. 84, 68–77 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Kluckow, M. Use of ultrasound in the haemodynamic assessment of the sick neonate. Arch. Dis. Child. Fetal Neonatal Ed. 99, F332–F337 (2014).

    Article  PubMed  Google Scholar 

  51. Kluckow, M., Seri, I. & Evans, N. Functional echocardiography: an emerging clinical tool for the neonatologist. J. Pediatr. 150, 125–130 (2007).

    Article  PubMed  Google Scholar 

  52. Mohsen, A. A. & Amin, A. Risk factors and outcomes of persistent pulmonary hypertension of the newborn in neonatal intensive care unit of al-minya University Hospital in Egypt. J. Clin. Neonatol. 2, 78–82 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Verma, B., Daga, S. R. & Mahapankar, A. Persistent pulmonary hypertension among neonates with sepsis. Indian J. Pediatr. 73, 250–251 (2006).

    Article  PubMed  Google Scholar 

  54. Dempsey, E. & Rabe, H. The use of cardiotonic drugs in neonates. Clin. Perinatol. 46, 273–290 (2019).

    Article  PubMed  Google Scholar 

  55. Sehgal, A., Athikarisamy, S. E. & Adamopoulos, M. Global myocardial function is compromised in infants with pulmonary hypertension. Acta Paediatr. 101, 410–413 (2012).

    Article  PubMed  Google Scholar 

  56. Moore, T. D. et al. Ventricular interaction and external constraint account for decreased stroke work during volume loading in CHF. Am. J. Physiol. Heart Circ. Physiol. 281, H2385–H2391 (2001).

    Article  CAS  PubMed  Google Scholar 

  57. Chagnon, F., Bentourkia, M., Lecomte, R., Lessard, M. & Lesur, O. Endotoxin-induced heart dysfunction in rats: assessment of myocardial perfusion and permeability and the role of fluid resuscitation*. Crit. Care Med. 34, 127–133 (2006).

    Article  CAS  PubMed  Google Scholar 

  58. Galiuto, L., Ignone, G. & DeMaria, A. N. Contraction and relaxation velocities of the normal left ventricle using pulsed-wave tissue Doppler echocardiography. Am. J. Cardiol. 81, 609–614 (1998).

    Article  CAS  PubMed  Google Scholar 

  59. Nagueh, S. F., Middleton, K. J., Kopelen, H. A., Zoghbi, W. A. & Quiñones, M. A. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J. Am. Collage Cardiol. 30, 1527–1533 (1997).

    Article  CAS  Google Scholar 

  60. Haileselassie, B. et al. Strain echocardiography parameters correlate with disease severity in children and infants with sepsis. Pediatr. Crit. Care Med. 17, 383–390 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Rivers, E. et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N. Engl. J. Med. 345, 1368–1377 (2001).

    Article  CAS  PubMed  Google Scholar 

  62. Nguyen, H. B. et al. Early goal-directed therapy in severe sepsis and septic shock: insights and comparisons to ProCESS, ProMISe, and ARISE. Crit. Care 20, 160 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Menon, K. et al. Criteria for pediatric sepsis-a systematic review and meta-analysis by the pediatric sepsis definition taskforce. Crit. Care Med. 50, 21–36 (2022).

    Article  PubMed  Google Scholar 

  64. Sullivan, B. A., Kausch, S. L. & Fairchild, K. D. Artificial and human intelligence for early identification of neonatal sepsis. Pediatr. Res. 93, 350–356 (2023).

    Article  PubMed  Google Scholar 

  65. Sahu, P. et al. Prediction modelling in the early detection of neonatal sepsis. World J. Pediatr. 18, 160–175 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the Italian Ministry of Health with “Current Research funds”.

Author information

Authors and Affiliations

  1. Research Area of Fetal, Neonatal, and Cardiological Sciences, Bambino Gesù Children Hospital, IRCCS, 00165, Rome, Italy

    Flaminia Pugnaloni & Pietro Bagolan

  2. Neonatal Intensive Care Unit, Bambino Gesù Children Hospital, IRCCS, 00165, Rome, Italy

    Domenico Umberto De Rose, Maria Paola Ronchetti, Andrea Dotta & Irma Capolupo

  3. PhD course in Microbiology, Immunology, Infectious Diseases, and Transplants (MIMIT), University of Rome “Tor Vergata”, 00133, Rome, Italy

    Domenico Umberto De Rose

  4. Department of Neonatology and Pediatric Intensive Care, Children’s Hospital, University of Bonn, Bonn, 53127, Germany

    Florian Kipfmueller

  5. Department of Neonatology, The Royal Hospital for Children, Glasgow, G51 4TF, UK

    Neil Patel

  6. Department of Systems Medicine, University of Rome “Tor Vergata”, 00133, Rome, Italy

    Pietro Bagolan

  7. Unicamillus-Saint Camillus International University of Health Sciences, Rome, Italy

    Cinzia Auriti

  8. Villa Margherita Private Clinic, Rome, Italy

    Cinzia Auriti

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  1. Flaminia Pugnaloni
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Contributions

F.P. and C.A. contributed to the study conception and design. Material preparation, data collection, and analysis were performed by F.P. and D.U.D.R. The first draft of the manuscript was written by F.P. and revised by D.U.D.R. N.P., F.K., M.P.R., A.D., P.B., and C.A. critically revised it for important intellectual content. All authors reviewed and approved the final version of the article.

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Correspondence to Domenico Umberto De Rose.

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Pugnaloni, F., De Rose, D.U., Kipfmueller, F. et al. Assessment of hemodynamic dysfunction in septic newborns by functional echocardiography: a systematic review. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03045-2

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