Neonatal septic shock, a focus on first line interventions

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Valentina Spaggiari
Erica Passini
Sara Crestani
Maria Federica Roversi
Luca Bedetti
Katia Rossi
Laura Lucaccioni
Cecilia Baraldi
Elisa Della Casa Muttini
Licia Lugli
Lorenzo Iughetti
Alberto Berardi


sepsis, newborn, septic shock, hemodynamic support, antibiotics


Septic shock is a main cause of morbidity and mortality in neonates. Septic shock evolves from compensated to uncompensated through 3 distinct phases. Prompt diagnosis is challenging, since neonatal septic shock may overlap with the physiological changes occurring at birth. The outcome of septic shock depends on a prompt recognition of symptoms and a strict adherence to cardiopulmonary resuscitation guidelines. Fluid administration plays a major role in the initial management of septic shock. If there is no response to volume filling, inotropes must be infused within one hour of onset (dopamine, dobutamine, adrenaline). Life-threatening infections require immediate and aggressive empiric use of antimicrobials. In the pediatric age, delay in antibiotic initiation for treating septic shock is associated with poor outcome and increased risk of mortality. There is a gap regarding first line interventions in neonatal septic shock. This review addresses initial interventions in the treatment of neonatal septic shock and discusses currently available evidences., These interventions may allow to improve the outcome if they are promptly carried out.


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1. Aneja RK, Varughese-Aneja R, Vetterly CG, et al. Antibiotic therapy in neonatal and pediatric septic shock. Curr Infect Dis Rep 2011;13:433-41.
2. Agyeman PKA, Schlapbach LJ, Giannoni E, et al. Pediatric Sepsis Study. Epidemiology of blood culture-proven bacterial sepsis in children in Switzerland: a population-based cohort study. Lancet Child Adolesc Health 2017;1:124-133.
3. Wynn JL, Wong HR. Pathophysiology and treatment of septic shock in neonates. Clin Perinatol 2010;37:439-79.
4. Wynn JL. Defining neonatal sepsis. Curr Opin Pediatr 2016;28:135-40.
5. Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet 201714;390:1770-1780.
6. Berardi A, Baroni L, Bacchi Reggiani ML, et al. GBS Prevention Working Group Emilia-Romagna. The burden of early-onset sepsis in Emilia-Romagna (Italy): a 4-year, population-based study. J Matern Fetal Neonatal Med 2016;29:3126-31.
7. Berardi A, Sforza F, Baroni L, et al. Epidemiology and complications of late-onset sepsis: an Italian area-based study. PLoS One 2019;14:e0225407.
8. Berardi A,Ficara M, Pietrella E, et al. Stewardship antimicrobica nel neonato e nel piccolo lattante. Perché e come praticarla, Medico e Bambino 2017;36:493-501,
9. Wilson CB, Nizet V, Maldonado YA et al. Infecious diseases of the fetus and newborn infant, Elsevier, 2016.
10. M. Barbara J. Stoll, M. P. Karen M. Puopolo, M. Nellie I. Hansen, et al. Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies. JAMA Pediatrics 2020;E1-E12.
11. Schrag SJ, Farley MM, Petit S, Reingold A, Weston EJ, et al. Epidemiology of Invasive Early-Onset Neonatal Sepsis, 2005 to 2014. Pediatrics 2016;138:e20162013.
12. Berardi A, Di Fazzio G, Gavioli S, et al. GBS Prevention Working Group, Emilia-Romagna. Universal antenatal screening for group B streptococcus in Emilia-Romagna. J Med Screen 2011;18:60-4.
13. Van Dyke MK, Phares CR, Schrag SJ et al. Evaluation of universal antenatal screening for group B streptococcus. N Engl J Med 2009;360:2626-36.
14. Vergnano S, Menson E, Kennea et al. Neonatal infections in England: the NeonIN surveillance network. Arch Dis Child Fetal Neonatal Ed 2011;96:F9-F14.
15. Cailes B, Kortsalioudaki C, Buttery J et al. Epidemiology of UK neonatal infections: the neonIN infection surveillance network. Arch Dis Child Fetal Neonatal Ed. 2018;103:F547-F553.
16. Pammi M, Weisman LE et al. Late-onset sepsis in preterm infants: update on strategies for therapy and prevention. Expert Rev Anti Infect Ther 2015;13:487-504.
17. Ficara M, Pietrella E, Spada C, et al. Changes of intestinal microbiota in early life. J Matern Fetal Neonatal Med 2020;33:1036-1043.
18. Richard Polin, Steven Abman. Fetal and Neonatal Physiology, Elsevier, Fifth Edition, vol. 1, 2016;1536-1551.
19. Goldstein B, Giroir B, Randolph A et al. International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005;6:2-8.
20. McGovern M, Giannoni E, Kuester H, et al. Infection, Inflammation, Immunology and Immunisation (I4) section of the ESPR. Challenges in developing a consensus definition of neonatal sepsis. Pediatr Res 2020;88:14-26.
21. Schlapbach LJ, MacLaren G, Festa M, et al. Australian & New Zealand Intensive Care Society (ANZICS) Centre for Outcomes & Resource Evaluation (CORE) and Australian & New Zealand Intensive Care Society (ANZICS) Paediatric Study Group. Prediction of pediatric sepsis mortality within 1 h of intensive care admission. Intensive Care Med 2017;43:1085-1096.
22. Schlapbach LJ, Kissoon N. Defining Pediatric Sepsis. JAMA Pediatr 2018;172:312-314.
23. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315:801-10.
24. Schlapbach LJ, Straney L, Bellomo R, et al. Prognostic accuracy of age-adapted SOFA, SIRS, PELOD-2, and qSOFA for in-hospital mortality among children with suspected infection admitted to the intensive care unit. Intensive Care Med 2018;44:179-188.
25. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013;369:2063.
26. Wynn JL, Polin RA. Progress in the management of neonatal sepsis: the importance of a consensus definition. Pediatr Res 2018;83:13-15.
27. Weiss SL, Peters MJ, Alhazzani W, et al. Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Pediatr Crit Care Med 2020;21:e52-e106.
28. Luthander J, Bennet R, Giske CG, et al. Trends of Pediatric Bloodstream Infections in Stockholm, Sweden: A 20-year Retrospective Study. Pediatr Infect Dis J 2020;39(12):1069-1074.
29. Carcillo JA. A synopsis of 2007 ACCM clinical practice parameters for hemodynamic support of term newborn and infant septic shock. Early Hum Dev 2014;S45-7.
30. Davis AL, Carcillo JA, Aneja RK, et al. American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock. Crit Care Med 2017;45:1061-1093.
31. Weiss SL, Keele L, Balamuth F, et al. Crystalloid Fluid Choice and Clinical Outcomes in Pediatric Sepsis: A Matched Retrospective Cohort Study. J Pediatr 2017;182:304-310.e10.
32. Emrath ET, Fortenberry JD, Travers C, et al. Resuscitation With Balanced Fluids Is Associated With Improved Survival in Pediatric Severe Sepsis. Crit Care Med 2017;45:1177-1183.
33. Arikan AA, Zappitelli M, Goldstein SL, et al. Fluid overload is associated with impaired oxygenation and morbidity in critically ill children. Pediatr Crit Care Med 2012;13:253-8.
34. Sankar J, Ismail J, Sankar MJ, et al. Fluid Bolus Over 15-20 Versus 5-10 Minutes Each in the First Hour of Resuscitation in Children With Septic Shock: A Randomized Controlled Trial. Pediatr Crit Care Med 2017;18:e435-e445.
35. Russell MJ, Kanthimathinathan HK. Is There an Optimum Duration of Fluid Bolus in Pediatric Septic Shock? A Critical Appraisal of "Fluid Bolus Over 15-20 Versus 5-10 Minutes Each in the First Hour of Resuscitation in Children With Septic Shock: A Randomized Controlled Trial" by Sankar et al (Pediatr Crit Care Med 2017; 18:e435-e445). Pediatr Crit Care Med 2018;19:369-371.
36. Seri I, Evans J. Controversies in the diagnosis and management of hypotension in the newborn infant. Curr Opin Pediatr 2001;13:116-23.
37. Gamper G, Havel C, Arrich J, et al. Vasopressors for hypotensive shock. Cochrane Database Syst Rev. 2016;2:CD003709.
38. De Backer D, Biston P, Devriendt J, et al. SOAP II Investigators. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010;362:779-89.
39. Avni T, Lador A, Lev S, et al. Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta-Analysis. PLoS One 201510:e0129305.
40. Baske K, Saini SS, Dutta S, et al. Epinephrine versus dopamine in neonatal septic shock: a double-blind randomized controlled trial. Eur J Pediatr 2018;177:1335-1342.
41. Gorantiwar S, de Waal K. Progression from sepsis to septic shock and time to treatments in preterm infants with late-onset sepsis. J Paediatr Child Health 2021. Epub ahead of print.
42. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34:1589-96.
43. Weiss SL, Fitzgerald JC, Balamuth F, et al. Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. Crit Care Med 2014;42:2409-17.
44. Evans IVR, Phillips GS, Alpern ER, et al. Association Between the New York Sepsis Care Mandate and In-Hospital Mortality for Pediatric Sepsis. JAMA 2018;320:358-367.
45. Schmatz M, Srinivasan L, Grundmeier RW, et al. Surviving Sepsis in a Referral Neonatal Intensive Care Unit: Association between Time to Antibiotic Administration and In-Hospital Outcomes. J Pediatr 2020;217:59-65.e1.
46. Bedetti L, Lugli L, Marrozzini L et al. Safety and Success of Lumbar Puncture in Young Infants: A Prospective Observational Study. Front Pediatr 2021;9:692652.
47. Berardi A, Zinani I, Rossi C, et al. Antibiotic Use in Very Low Birth Weight Neonates After an Antimicrobial Stewardship Program. Antibiotics (Basel) 2021;10:411.
48. Cantey JB, Patel SJ. Antimicrobial stewardship in the NICU. Infect Dis Clin North Am 2014;28:247-61.