Resource-rich settings
●
Rapid recognition – Each pediatric institution should develop and employ a septic shock screening tool ( algorithm 2) to support rapid assessment and resuscitation of children with suspected septic shock. (See 'Institutional approach' above.)
•
A clinical diagnosis of severe sepsis or septic shock is made in children who have signs of inadequate tissue perfusion, two or more criteria for the systemic
inflammatory response syndrome ( table 1), and suspected or proven infection.
(See 'Red-flag findings' above and 'Signs and symptoms of infection' above.) Approach – Our approach to initial stabilization and treatment of children with septic shock in settings with access to intensive care is shown in the algorithm ( algorithm 1) and is largely consistent with the 2020 Surviving Sepsis
Campaign guidelines provided by the initial resuscitation algorithm for children. (See 'Approach' above and 'Institutional guidelines and protocols' above.)
•
Fluid resuscitation – Children with septic shock and no signs of fluid overload should receive 10 to 20 mL/kg of balanced crystalloid solution (eg, Lactated Ringer solution) or normal saline. Fluid volume should be calculated based upon ideal body weight (eg, 50 percentile for age ( figure 1A-B and figure 2A-B)).
We suggest using balanced crystalloid fluids (eg, Lactated Ringer or multiple electrolyte solutions such as PlasmaLyte) for fluid resuscitation, although 0.9%
saline remains an effective alternative (Grade 2C). Infusion of this amount of fluid over 5 to 10 minutes can be achieved with a manual "push-pull" technique or
•
th
rapid infuser. (See 'Fluid resuscitation' above.)
For patients who develop signs of fluid overload (eg, rales, worsening respiratory distress, new or worsening oxygen requirement, gallop rhythm, hepatomegaly, or cardiomegaly or pulmonary edema on chest radiograph), omit or reduce the fluid bolus (eg, 5 to 10 mL/kg given over 15 minutes); treat persistent shock with
vasoactive infusions. (See 'Fluid resuscitation' above.)
After the initial infusion, quickly reassess the patient for continued shock and/or signs of fluid overload (eg, pulmonary rales or gallop rhythm). If each fluid bolus provides hemodynamic improvement, then fluid resuscitation should still
continue until tissue perfusion, oxygen delivery, and blood pressure are adequate or signs of fluid overload develop. (See 'Resource-rich settings' above.)
Fluid refractory shock – For children who continue to have evidence of abnormal perfusion after 40 to 60 mL/kg of crystalloid fluid resuscitation, we suggest
initiation of vasoactive therapy (eg, continuous infusion of epinephrine ( table 5 and table 6) or norepinephrine). The choice of agent is determined by whether the blood pressure is normal or hypotensive for age ( table 1) (see 'Indications for vasoactive agents' above):
•
Hypotensive shock – For children with fluid-refractory, hypotensive septic shock, we suggest vasoactive therapy with either an epinephrine infusion or norepinephrine infusion rather than a dopamine infusion (Grade 2C). (See 'Hypotensive patients' above.)
-
Normotensive shock – For children with fluid-refractory, normotensive septic shock, we suggest vasoactive therapy with low-dose epinephrine infusion rather than norepinephrine or dopamine (Grade 2C). (See 'Normotensive patients' above.)
-
Central venous access is preferred for vasoactive therapy. However, peripheral intravenous (IV) access or intraosseous (IO) cannula is acceptable during initial resuscitation, while central venous access is being obtained or, in less ill patients, the need for central venous access becomes clear.
Empiric antimicrobial therapy – Start antimicrobial therapy within the first hour of resuscitation (see 'Timing' above). Antifungal and antiviral agents should be included as part of the initial regimen for susceptible patients. (See 'Empiric antibiotic therapy' above.)
•
Adrenal insufficiency – Treat patients at risk for absolute adrenal insufficiency with stress-dose hydrocortisone early in the course of resuscitation. (See 'Patients at risk for adrenal insufficiency' above.)
•
Catecholamine-resistant shock – Evaluate patients with catecholamine-resistant shock for unrecognized morbidities such as pneumothorax, pericardial effusion, intra-abdominal hypertension, and ongoing blood loss. In addition, for previously healthy patients who persist with catecholamine-resistant shock, we suggest stress-dose corticosteroid therapy ( table 10) (Grade 2C). However, because definitive evidence of benefit in children is lacking, ongoing management without corticosteroid therapy is a reasonable alternative. (See 'Patients with
catecholamine-resistant shock' above.)
•
Ongoing management – After initial resuscitation, continue management in a pediatric intensive care unit directed by a pediatric critical care specialist. (See 'Transfer to definitive care' above and "Septic shock in children: Ongoing management after resuscitation".)
•
Resource-limited settings
●
In resource-limited settings without access to intensive care with advanced airway and circulatory support, modify treatment of sepsis or septic shock based on either hypotension or the World Health Organization (WHO) definition of shock as provided by the initial resuscitation algorithm for children (see 'Resource- limited settings' above):
•
Severe sepsis – Patients with severe febrile illness, poor perfusion, and, if measured, normal blood pressure should receive maintenance fluids and not bolus fluid resuscitation.
-
Septic shock – In patients with septic shock and hypotension, bolus fluids should be administered judiciously in aliquots of 10 to 20 mL/kg up to 40 mL/kg in the first hour with volume and rate titrated to cardiac output and discontinued if the patient develops clinical signs of fluid overload.
-
Patients with dehydration or ongoing fluid losses (eg, diarrhea or severe capillary leak as with dengue shock syndrome) should receive fluid therapy according to the WHO Emergency Triage Assessment and Treatment guidelines ( table 7).
(See "Dengue virus infection: Prevention and treatment", section on 'Management of plasma leakage'.)
•
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REFERENCES
1. Weiss SL, Peters MJ, Alhazzani W, et al. Executive Summary: Surviving Sepsis
Campaign International Guidelines for the Management of Septic Shock and Sepsis- Associated Organ Dysfunction in Children. Pediatr Crit Care Med 2020; 21:186.
2. 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.
3. 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.
4. Han YY, Carcillo JA, Dragotta MA, et al. Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome. Pediatrics 2003; 112:793.
5. 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.
6. Cruz AT, Perry AM, Williams EA, et al. Implementation of goal-directed therapy for children with suspected sepsis in the emergency department. Pediatrics 2011;
127:e758.
7. Paul R, Melendez E, Stack A, et al. Improving adherence to PALS septic shock guidelines. Pediatrics 2014; 133:e1358.
8. Kleinman ME, de Caen AR, Chameides L, et al. Pediatric basic and advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and
Emergency Cardiovascular Care Science with Treatment Recommendations. Pediatrics 2010; 126:e1261.
9. Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med 2021;
49:e1063.
10. Dugas MA, Proulx F, de Jaeger A, et al. Markers of tissue hypoperfusion in pediatric septic shock. Intensive Care Med 2000; 26:75.
11. Scott HF, Brou L, Deakyne SJ, et al. Lactate Clearance and Normalization and Prolonged Organ Dysfunction in Pediatric Sepsis. J Pediatr 2016; 170:149.
12. Bai Z, Zhu X, Li M, et al. Effectiveness of predicting in-hospital mortality in critically ill
children by assessing blood lactate levels at admission. BMC Pediatr 2014; 14:83.
13. Velissaris D, Pierrakos C, Scolletta S, et al. High mixed venous oxygen saturation levels do not exclude fluid responsiveness in critically ill septic patients. Crit Care 2011;
15:R177.
14. Fink MP. Bench-to-bedside review: Cytopathic hypoxia. Crit Care 2002; 6:491.
15. Dueck MH, Klimek M, Appenrodt S, et al. Trends but not individual values of central venous oxygen saturation agree with mixed venous oxygen saturation during varying hemodynamic conditions. Anesthesiology 2005; 103:249.
16. Lane RD, Funai T, Reeder R, Larsen GY. High Reliability Pediatric Septic Shock Quality Improvement Initiative and Decreasing Mortality. Pediatrics 2016; 138.
17. Workman JK, Ames SG, Reeder RW, et al. Treatment of Pediatric Septic Shock With the Surviving Sepsis Campaign Guidelines and PICU Patient Outcomes. Pediatr Crit Care Med 2016; 17:e451.
18. Asfar P, Calzia E, Huber-Lang M, et al. Hyperoxia during septic shock--Dr. Jekyll or Mr.
Hyde? Shock 2012; 37:122.
19. Wolfler A, Calderini E, Iannella E, et al. Evolution of Noninvasive Mechanical
Ventilation Use: A Cohort Study Among Italian PICUs. Pediatr Crit Care Med 2015;
16:418.
20. Dohna-Schwake C, Stehling F, Tschiedel E, et al. Non-invasive ventilation on a pediatric intensive care unit: feasibility, efficacy, and predictors of success. Pediatr Pulmonol 2011; 46:1114.
21. Pancera CF, Hayashi M, Fregnani JH, et al. Noninvasive ventilation in
immunocompromised pediatric patients: eight years of experience in a pediatric oncology intensive care unit. J Pediatr Hematol Oncol 2008; 30:533.
22. den Brinker M, Joosten KF, Liem O, et al. Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality. J Clin Endocrinol Metab 2005;
90:5110.
23. den Brinker M, Hokken-Koelega AC, Hazelzet JA, et al. One single dose of etomidate negatively influences adrenocortical performance for at least 24h in children with meningococcal sepsis. Intensive Care Med 2008; 34:163.
24. Damman J, Arias P, Kerner J, et al. Procalcitonin as a Predictive Marker for Bacteremia in Children With a Central Line and Fever. Hosp Pediatr 2019; 9:434.
25. Kasem AJ, Bulloch B, Henry M, et al. Procalcitonin as a marker of bacteremia in
children with fever and a central venous catheter presenting to the emergency department. Pediatr Emerg Care 2012; 28:1017.
26. von Lilienfeld-Toal M, Dietrich MP, Glasmacher A, et al. Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein. Eur J Clin Microbiol Infect Dis 2004; 23:539.
27. Kuppermann N, Dayan PS, Levine DA, et al. A Clinical Prediction Rule to Identify
Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections. JAMA Pediatr 2019; 173:342.
28. Gomez B, Mintegi S, Bressan S, et al. Validation of the "Step-by-Step" Approach in the Management of Young Febrile Infants. Pediatrics 2016; 138.
29. Sanchez GJ, Venkataraman PS, Pryor RW, et al. Hypercalcitoninemia and hypocalcemia in acutely ill children: studies in serum calcium, blood ionized calcium, and calcium- regulating hormones. J Pediatr 1989; 114:952.
30. Forsythe RM, Wessel CB, Billiar TR, et al. Parenteral calcium for intensive care unit patients. Cochrane Database Syst Rev 2008; :CD006163.
31. Kovacs A, Courtois MR, Barzilai B, et al. Reversal of hypocalcemia and decreased afterload in sepsis. Effect on myocardial systolic and diastolic function. Am J Respir Crit Care Med 1998; 158:1990.
32. Porcelli PJ Jr, Oh W. Effects of single dose calcium gluconate infusion in hypocalcemic preterm infants. Am J Perinatol 1995; 12:18.
33. Carcillo JA, Davis AL, Zaritsky A. Role of early fluid resuscitation in pediatric septic shock. JAMA 1991; 266:1242.
34. Raman S, Peters MJ. Fluid management in the critically ill child. Pediatr Nephrol 2014;
29:23.
35. Sankar J, Muralidharan J, Lalitha AV, et al. Multiple Electrolytes Solution Versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial. Crit Care Med 2023.
36. 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.
37. 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.
38. Chopra A, Kumar V, Dutta A. Hypertonic versus normal saline as initial fluid bolus in pediatric septic shock. Indian J Pediatr 2011; 78:833.
39. WHO Guideline: Updates on Paediatric Emergency Triage, Assessment and Treatment : Care of Critically-ill Children. Geneva, Switzerland, World Health Organization, 2016.
https://apps.who.int/iris/bitstream/handle/10665/204463/9789241510219_eng.pdf (A ccessed on October 03, 2022).
40. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011; 364:2483.
41. 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.
42. Kortz T, Kissoon N. Fluid Resuscitation in Pediatric Septic Shock: The Case Against Haste. Pediatr Crit Care Med 2017; 18:995.
43. Myburgh JA. Fluid resuscitation in acute illness--time to reappraise the basics. N Engl J Med 2011; 364:2543.
44. Maitland K, George EC, Evans JA, et al. Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial. BMC Med 2013; 11:68.
45. Myburgh J, Finfer S. Causes of death after fluid bolus resuscitation: new insights from FEAST. BMC Med 2013; 11:67.
46. Haque IU, Zaritsky AL. Analysis of the evidence for the lower limit of systolic and mean arterial pressure in children. Pediatr Crit Care Med 2007; 8:138.
47. 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.
48. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med 2017;
45:486.
49. Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48:503.
50. Peshimam N, Bruce-Hickman K, Crawford K, et al. Peripheral and
Central/Intraosseous Vasoactive Infusions During and After Pediatric Critical Care Transport: Retrospective Cohort Study of Extravasation Injury. Pediatr Crit Care Med 2022; 23:626.
51. Owen VS, Rosgen BK, Cherak SJ, et al. Adverse events associated with administration of vasopressor medications through a peripheral intravenous catheter: a systematic
review and meta-analysis. Crit Care 2021; 25:146.
52. D'Souza M, Pye S, Randle E, et al. Use of peripheral vasoactive drug infusions during the critical care transport of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection. Arch Dis Child 2022;
107:e11.
53. Turner DA, Kleinman ME. The use of vasoactive agents via peripheral intravenous access during transport of critically III infants and children. Pediatr Emerg Care 2010;
26:563.
54. Levy RA, Reiter PD, Spear M, et al. Peripheral Vasoactive Administration in Critically Ill Children With Shock: A Single-Center Retrospective Cohort Study. Pediatr Crit Care Med 2022; 23:618.
55. Deep A, Goonasekera CD, Wang Y, Brierley J. Evolution of haemodynamics and outcome of fluid-refractory septic shock in children. Intensive Care Med 2013;
39:1602.
56. Pediatric Advanced Life Support Provider Manual, Chameides L, Samson RA, Schexnay der SM, Hazinski MF (Eds), American Heart Association, Dallas 2012.
57. Walker SB, Conlon TW, Zhang B, et al. Clinical Signs to Categorize Shock and Target Vasoactive Medications in Warm Versus Cold Pediatric Septic Shock. Pediatr Crit Care Med 2020; 21:1051.
58. Ventura AM, Shieh HH, Bousso A, et al. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock. Crit Care Med 2015; 43:2292.
59. Ramaswamy KN, Singhi S, Jayashree M, et al. Double-Blind Randomized Clinical Trial Comparing Dopamine and Epinephrine in Pediatric Fluid-Refractory Hypotensive Septic Shock. Pediatr Crit Care Med 2016; 17:e502.
60. Branco RG. Dopamine in Sepsis-Beginning of the End? Pediatr Crit Care Med 2016;
17:1099.
61. Ranjit S, Aram G, Kissoon N, et al. Multimodal monitoring for hemodynamic categorization and management of pediatric septic shock: a pilot observational study*. Pediatr Crit Care Med 2014; 15:e17.
62. Odetola FO, Gebremariam A, Freed GL. Patient and hospital correlates of clinical
outcomes and resource utilization in severe pediatric sepsis. Pediatrics 2007; 119:487.
63. Watson RS, Carcillo JA, Linde-Zwirble WT, et al. The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med 2003; 167:695.
64. Weiss SL, Parker B, Bullock ME, et al. Defining pediatric sepsis by different criteria:
discrepancies in populations and implications for clinical practice. Pediatr Crit Care Med 2012; 13:e219.
65. Jaramillo-Bustamante JC, Marín-Agudelo A, Fernández-Laverde M, Bareño-Silva J.
Epidemiology of sepsis in pediatric intensive care units: first Colombian multicenter study. Pediatr Crit Care Med 2012; 13:501.
66. Eisenberg MA, Riggs R, Paul R, et al. Association Between the First-Hour Intravenous Fluid Volume and Mortality in Pediatric Septic Shock. Ann Emerg Med 2022; 80:213.
67. Inwald DP, Tasker RC, Peters MJ, et al. Emergency management of children with severe sepsis in the United Kingdom: the results of the Paediatric Intensive Care Society sepsis audit. Arch Dis Child 2009; 94:348.
68. Weiss SL, Fitzgerald JC, Pappachan J, et al. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med 2015; 191:1147.
69. Schlapbach LJ, Straney L, Alexander J, et al. Mortality related to invasive infections, sepsis, and septic shock in critically ill children in Australia and New Zealand, 2002-13:
a multicentre retrospective cohort study. Lancet Infect Dis 2015; 15:46.
70. Kutko MC, Calarco MP, Flaherty MB, et al. Mortality rates in pediatric septic shock with and without multiple organ system failure. Pediatr Crit Care Med 2003; 4:333.
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