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Paediatric Drugs

, Volume 3, Issue 1, pp 9–27 | Cite as

Management of Sepsis and Septic Shock in Infants and Children

  • Niels von Rosenstiel
  • Ines von Rosenstiel
  • Dieter Adam
Review Article

Abstract

Sepsis and septic shock constitute an important cause of morbidity and mortality in critically ill children. Thus, the systemic response to infection and its management remains a major challenge in clinical medicine. Apart from antibiotic administration, the majority of available therapies are limited to supportive strategies, although considerable efforts are being undertaken to devise innovative approaches that modulate host inflammatory responses.

In suspected sepsis, 2 or 3 days’ empiric antibiotic therapy should begin immediately after cultures have been obtained without awaiting results. Antibiotics should be re-evaluated when the results of the cultures and susceptibility tests are available. The initial antibiotic (combination) is determined by the likely causative agent, susceptibility patterns within a specific institution, CNS penetration, toxicity, and the patient’s hepatic and renal function. The likely offending microorganism in turn depends primarily on the patient’s age, coexistence of any premorbid condition leading to impaired immune response, and the presenting signs and symptoms.

Close attention to cardiovascular, respiratory, fluid and electrolyte, haematological, renal and metabolic/nutritional support is essential to optimise outcome. Fluid resuscitation is of utmost importance to overcome hypovolaemia on the basis of a diffuse capillary leak. Monitoring and normalisation of the heart rate is essential. In case of nonresponse to fluid resuscitation, inotropic and vasoactive agents are commonly used to increase cardiac output, maintain adequate blood pressure and enhance oxygen delivery to the tissue. Because respiratory distress syndrome is seen in about 40% of critically ill children with septic shock, increased inspired oxygen is essential. To provide optimal relief from respiratory muscle fatigue and facilitate the provision of positive airway pressure, early intubation and mechanical ventilation should be considered. Renal support is essential to avoid prolonged renal shutdown in hypoperfusion states. Haematological support comprises replacement therapy of clotting factors to overcome disseminated intravascular coagulation. Metabolic support may include glucose support, extraction of ammonia from the body and recognition of liver dysfunction. Nutritional support may modify the inflammatory host response, and early enteral feeding can improve outcome in critical illness. To date, glucocorticoid and non-glucocorticoid anti-inflammatory agents have not shown significant benefit in septic patients.

Keywords

Septic Shock Disseminate Intravascular Coagulation Milrinone Amrinone Lipopolysaccharide Binding Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Bone RC, Balk RA, Cerra FB, et al. ACCP/SCCM consensus conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992; 101: 1644–55PubMedCrossRefGoogle Scholar
  2. 2.
    Brandtzaeg P, Kierulf P, Gaustad P, et al. Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease. J Infect Dis 1989; 159(2): 195–204PubMedCrossRefGoogle Scholar
  3. 3.
    Parillo J. Pathogenic mechanisms of septic shock. N Engl J Med 1993; 328: 1471–7CrossRefGoogle Scholar
  4. 4.
    Saez Llorens X, McCracken G. Sepsis syndrome and septic shock in pediatrics: current concepts of terminology, pathophysiology, and management. J Pediatr 1993; 123: 497–508PubMedCrossRefGoogle Scholar
  5. 5.
    Hayden WR. Sepsis terminology in pediatrics. J Pediatr 1994; 124: 657–8PubMedGoogle Scholar
  6. 6.
    Ashkenazi S, Leibovici L, Samra Z, et al. Risk factors for mortality due to bacteremia and fungemia in childhood. Clin Infect Dis 1992; 14(4): 949–51PubMedCrossRefGoogle Scholar
  7. 7.
    Bell LM, Baker MD, Beatty D, et al. Infections in severely traumatized children. J Pediatr Surg 1992; 27(11): 1394–8PubMedCrossRefGoogle Scholar
  8. 8.
    Jafari HS, McCracken GHJ. Sepsis and septic shock: a review for clinicians. Pediatr Infect Dis J 1992; 11(9): 739–48PubMedCrossRefGoogle Scholar
  9. 9.
    Hazelzet JA, de Groot R. Sepsis-related problems in pediatric patients. In: Reinhart K, Eyrich K, Sprung C, editors. Update in intensive care and emergency medicine 18. Sepsis. Current perspectives in pathology and therapy. Berlin, Heidelberg: Springer-Verlag, 1994: 217–27Google Scholar
  10. 10.
    Ferrieri P. Neonatal susceptibility and immunity to major bacterial pathogens. Rev Infect Dis 1990; 12Suppl. 4: S394–400PubMedCrossRefGoogle Scholar
  11. 11.
    Gerdes JS. Clinicopathologic approach to the diagnosis of neonatal sepsis. Clin Perinatol 1991; 18: 361–81PubMedGoogle Scholar
  12. 12.
    Gladstone IM, Ehrenkranz RA, Edberg SC, et al. A ten-year review of neonatal sepsis and comparison with the previous fifty-year experience. Pediatr Infect Dis J 1990; 9: 819–25PubMedCrossRefGoogle Scholar
  13. 13.
    Carcillo JA, Davis AL, Zaritsky A. Role of early fluid resuscitation in pediatric septic shock. JAMA 1991; 266(9): 1242–5PubMedCrossRefGoogle Scholar
  14. 14.
    Jacobs RF, Sowell MK, Moss MM, et al. Septic shock in children: bacterial etiologies and temporal relationships. Pediatr Infect Dis J 1990, 9(3): 196–200PubMedCrossRefGoogle Scholar
  15. 15.
    Romano MJ, Kearns GL, Kaplan SL. Single-dose pharmacokinetics and safety of HA-1A, a human IgM anti-lipid A monoclonal antibody, in pediatric patients with sepsis syndrome. J Pediatr 1993; 122: 974–81PubMedCrossRefGoogle Scholar
  16. 16.
    Storgion SA, Beck RJ, Leggiadro RJ. Frequency and outcome of infections disease admissions to a pediatric intensive care unit. South Med J 1994; 87: 1121–4PubMedCrossRefGoogle Scholar
  17. 17.
    Stein F, Tervino R. Nosocomial infections in the pediatric intensive care unit. Pediatr Clin North Am 1994; 41: 1245–57PubMedGoogle Scholar
  18. 18.
    Bayston K, Cohen J. Bacterial endotoxin and current concepts in the diagnosis and treatment of endotoxaemia. J Med Microbiol 1990; 31: 73–83PubMedCrossRefGoogle Scholar
  19. 19.
    Tolan Jr RW. Toxic shock syndrome complicating influenza A in a child: case and review. Clin Infect Dis 1993; 17: 43–5PubMedCrossRefGoogle Scholar
  20. 20.
    Chesney P, Chesney R. Hemorrhagic shock and encephalopathy: reflections about a new devastating disorder that affects normal children. J Pediatr 1989; 114(2): 254–6PubMedCrossRefGoogle Scholar
  21. 21.
    Zangwill KM, Schuchat A, Wenger JD. Group B streptococcal disease in the United States, 1990: report from a multistate active surveillance system. MMWR CDC Surveill Summ 1992; 41(6): 25–32PubMedGoogle Scholar
  22. 22.
    Barriere SL, Lowry SF. An overview of mortality risk prediction in sepsis. Crit Care Med 1995; 23: 376–93PubMedCrossRefGoogle Scholar
  23. 23.
    Bone RC. Clinical manifestations and prognostic indicators in sepsis. In: Reinhart K, Eyrich K, Sprung C, editors. Update in intensive care and emergency medicine 18. Sepsis. Current perspectives in pathology and therapy. Berlin, Heidelberg: Springer-Verlag, 1994: 16–22Google Scholar
  24. 24.
    Vincent JL. The ‘at risk’ patient population. In: Sibbald WJ, Vincent JL, editors. Update in intensive care and emergency medicine 19. Clinical trials for the treatment of sepsis. Berlin, Heidelberg: Springer-Verlag, 1995: 13–34Google Scholar
  25. 25.
    Zimmermann JJ, Dietrich KA. Current perspectives on septic shock. Pediatr Clin North Am 1987; 34: 131–63Google Scholar
  26. 26.
    Stopfkuchen H. Neonatal sepsis. In: Tibboel D, van der Voort E, editors. Intensive care in childhood. A challenge to the future. Berlin, Heidelberg: Springer-Verlag, 1996: 219–28CrossRefGoogle Scholar
  27. 27.
    D’Andrea CC, Ferrera PC. Disseminated herpes simplex virus infection in a neonate. Am J Emerg Med 1998; 16(4): 376–8PubMedCrossRefGoogle Scholar
  28. 28.
    Ramilo O, Siegel JD. Sepsis. In: Levin DL, Morris FC, editors. Essentials of pediatric intensive care. St. Louis: Quality Medical Publ., 1990: 343–52Google Scholar
  29. 29.
    Eley B, Levin M. Septic shock with special reference to meningococcal disease. Curr Opin Infect Dis 1994; 7: 345–50CrossRefGoogle Scholar
  30. 30.
    Kornellisse RF, Hazelzet JA, Hop WCJ, et al. Meningococcal septic shock in children: clinical and laboratory features, outcome, and development of a prognostic score. Clin Infect Dis 1997; 25: 640–6CrossRefGoogle Scholar
  31. 31.
    Needleman JP, Ackerman AD. Overwhelming sepsis. In: Rogers MC, Nichols DG, editors. Textbook of pediatric intensive care. Baltimore (MD): Williams & Wilkins, 1999: 1011–38Google Scholar
  32. 32.
    Yurdakok M. Antibiotic use in neonatal sepsis. Turk J Pediatr 1998; 40(1): 17–33PubMedGoogle Scholar
  33. 33.
    Goldman DA. Bacterial colonization and infection in the neonate. Am J Med 1981; 70: 417CrossRefGoogle Scholar
  34. 34.
    Leonard EM, van Saene HKF, Shears P, et al. Pathogenesis of colonization and infection in a neonatal surgical unit. Crit Care Med 1990; 18: 264–9PubMedCrossRefGoogle Scholar
  35. 35.
    Schenep JL, Hughes WT, Roberson PK, et al. Vancomycin, ticarcillin, and amikacin compared with ticarcillin-clavulanate and amikacin in the empirical treatment of febrile neutropenic children with cancer. N Engl J Med 1988; 319: 1053–8CrossRefGoogle Scholar
  36. 36.
    The EORTC International Antimicrobial Therapy Cooperative Group. Ceftazidime combined with short or long course of amikacin for empirical therapy of gram-negative bacteremia in cancer patients with granulocytopenia. N Engl J Med 1987; 317: 1692–8CrossRefGoogle Scholar
  37. 37.
    Olson TA, Fisher GW, Lupo MC, et al. Antimicrobial therapy of broviac catheter infections in pediatric hematology oncology patients. J Pediatr Surg 1987; 22: 839–42PubMedCrossRefGoogle Scholar
  38. 38.
    Bragman S, Sage R, Booth L, et al. Ceftazidime in the treatment of serious Pseudomonas aeruginosa sepsis. Scand J Infect Dis 1986; 18: 425–9PubMedCrossRefGoogle Scholar
  39. 39.
    Johnson MP, Ramphal R. Beta-lactam-resistant Enterobacter bacteremia in febrile neutropenic patients receiving monotherapy. J Infect Dis 1990; 162: 981–3PubMedCrossRefGoogle Scholar
  40. 40.
    Bonatti H, Guggenbichler JP, Hager J. Treatment of nosocomial infections in children undergoing antimicrobial chemotherapy. Infection 1990; 18: 302–6PubMedCrossRefGoogle Scholar
  41. 41.
    Moellering RC, Eliopoulos GM, Sentochnik DE. The carbapenems: new broad spectrum β-lactam antibiotics. J Antimicrob Chemother 1989; 24Suppl. A: I–7Google Scholar
  42. 42.
    Ceneviva G, Paschall JA, Maffei F, et al. Hemodynamic support in fluid-refractory pediatric septic shock. Pediatrics 1998; 102(2): 19–31CrossRefGoogle Scholar
  43. 43.
    Mercier J-C, Beaufils F, Hartmann J-F, et al. Hemodynamic patterns of meningococcal shock in children. Crit Care Med 1988; 16(1): 27–33PubMedCrossRefGoogle Scholar
  44. 44.
    Carcillo JA, Pollack MM, Ruttimann UE, et al. Sequential physiologic interactions in pediatric cardiogenic and septic shock. Crit Care Med 1989; 17(1): 12–6PubMedCrossRefGoogle Scholar
  45. 45.
    Chio PTL, Gordon Y, Quinonez LG, et al. Crystalloids vs. colloids in fluid resuscitation: a systemic review. Crit Care Med 1999; 27(1): 200–3CrossRefGoogle Scholar
  46. 46.
    Soni N. Wonderful albumin? BMJ 1995; 10: 887–8CrossRefGoogle Scholar
  47. 47.
    Fleck A, Raines G, Hawker F, et al. Increased vascular permeability: a major cause of hypoalbuminaemia in disease and injury. Lancet 1985; 1: 781–4PubMedCrossRefGoogle Scholar
  48. 48.
    Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients: systemic review of randomised controlled trial. BMJ 1998; 317: 235–40CrossRefGoogle Scholar
  49. 49.
    Gill AB, Weindling AM. Echocardiographic assessment of cardiac function in shocked very low birthweight infants. Arch Dis Child 1993; 68Suppl. 1: 17–21PubMedCrossRefGoogle Scholar
  50. 50.
    Perkin RM, Levin DC, Webb R, et al. Dobutamine: a hemodynamic evaluation in children with shock. J Pediatr 1982; 10: 977Google Scholar
  51. 51.
    Ruiz CE, Weit MH, Carlson RW. Treatment of circulatory shock with dopamine. JAMA 1979; 242: I65CrossRefGoogle Scholar
  52. 52.
    Seri I. Cardiovascular, renal and endocrine actions of dopamine in neonates and children. J Pediatr 1995; 126(3): 333PubMedCrossRefGoogle Scholar
  53. 53.
    Jewitt D, Birkhead J, Mitchell A, et al. Clinical cardiovascular pharmacology of dobutamine. A selective inotrope catecholamine. Lancet 1974; 2: 363PubMedCrossRefGoogle Scholar
  54. 54.
    Vincent JL, Roman A, Kahn RJ. Dobutamine administration in septic shock: addition to a standard protocol. Crit Care Med 1990; 18: 689–93PubMedCrossRefGoogle Scholar
  55. 55.
    Sakamata T, Yamada T. Hemodynamic effects of dobutamine on patients following open heart surgery. Circulation 1977; 55: 525CrossRefGoogle Scholar
  56. 56.
    Schaer GL, Mitchell PF, Parillo JE. Norepinephrine alone versus norepinephrine plus low dose dopamine. Enhanced renal blood flow with combination pressor therapy. Crit Care Med 1985; 13: 492PubMedCrossRefGoogle Scholar
  57. 57.
    Alousi AA, Johnson DC. Pharmacology of the bipyridines: amrinone and milrinone. Circulation 1986; 73Suppl. 3: 10–24Google Scholar
  58. 58.
    Young RA, Ward A. Milrinone: a preliminary review of its pharmacological properties and therapeutic use. Drugs 1988; 36: 158–92PubMedCrossRefGoogle Scholar
  59. 59.
    Earl CQ, Linden J. Biochemical mechanisms for the inotropic effect of the cardiotonic drug milrinone. J Cardiovasc Pharmacol 1986; 8: 864–72PubMedGoogle Scholar
  60. 60.
    Lindsay CA, Barton P, Lawless S, et al. Pharmacokinetics and pharmacodynamics of milrinone lactate in pediatric patients with septic shock. J Pediatrics 1998; 132: 329–34CrossRefGoogle Scholar
  61. 61.
    Heinz G, Geppert A, Delle Karth G, et al. IV milrinone for cardiac output increases and maintenance: comparison in non-hyperdynamic SIRS/sepsis and congestive heart failure. Int Care Med 1999; 25: 620–4CrossRefGoogle Scholar
  62. 62.
    Barton P, Garcia J, Kouatli A, et al. Hemodynamic effects of milrinone lactate in pediatric patients with septic shock: a prospective, double-blinded, randomized, placebo-controlled, interventional study. Chest 1996; 109: 1302–12PubMedCrossRefGoogle Scholar
  63. 63.
    Applebaum A, Blackstone EH, Kouchoukos NT, et al. Afterload reduction and cardiac output in infants early after intracardiac surgery. Am J Cardiol 1977; 39: 445CrossRefGoogle Scholar
  64. 64.
    Benson LN, Bohn D, Edmonds JF, et al. Nitroglycerin therapy in children with low cardia index after heart surgery. Cardiovasc Med 1979; 4: 207Google Scholar
  65. 65.
    Lock JE, Olley PM, Ceceani E, et al. Use of prostacyclin in persistent fetal circulation. Lancet 1979; 2: I343Google Scholar
  66. 66.
    Hayes MA, Timmens AC, Yau EHS, et al. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994; 330: 1717–22PubMedCrossRefGoogle Scholar
  67. 67.
    Lyrine RK, Trung WE. Adult respiratory distress syndrome in a pediatric intensive care unit: predisposing conditions, clinical course and outcome. Pediatrics 1981; 67: 790Google Scholar
  68. 68.
    McCune S, Short BL, Miller MK, et al. Extracorporeal membrane oxygenation therapy in neonates with septic shock. J Pediatr Surg 1990; 25: 479PubMedCrossRefGoogle Scholar
  69. 69.
    Beca J, Butt W. Extracorporeal membrane oxygenation for refractory septic shock in children. Pediatrics 1994; 93: 726–9PubMedGoogle Scholar
  70. 70.
    Champion MP, Murdoch IA, Sajjanhar T, et al. Extracorporeal membrane oxygenation for refractory shock in fulminant meningococcal sepsis. Lancet 1996; 374: 201–2CrossRefGoogle Scholar
  71. 71.
    Goldman AP, Kerr SJ, Butt W, et al. Extracorporeal support for intractable cardiorespiratory failure due to meningococcal disease. Lancet 1997; 349: 466–9PubMedCrossRefGoogle Scholar
  72. 72.
    Andrew M, Paes B, Milner R, et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70(1): 165–72PubMedGoogle Scholar
  73. 73.
    Leclerc F, Hazelzet JA, Jude B, et al. Protein C and S deficiency in severe infectious purpura of children: a collaborative study of 40 cases. Intens Care Med 1992; 18(4): 202–5CrossRefGoogle Scholar
  74. 74.
    Curley MA, Castillo L. Nutrition and shock in pediatric patients. New Horizon 1998; 6: 212–25Google Scholar
  75. 75.
    Ziegler TR, Leader LM, Jonas CR, et al. Adjunctive therapies in nutritional support. Nutrition 1997; 13: 64S–72SPubMedCrossRefGoogle Scholar
  76. 76.
    Castillo L, Yu YM, Marchini JS, et al. Phenylalanine and thyrosine kinetics in critically ill children with sepsis. Pediatrics 1994; 35: 580–8Google Scholar
  77. 77.
    Takala J, Ruokonen E, Webster NR, et al. Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 1999; 341: 785–92PubMedCrossRefGoogle Scholar
  78. 78.
    Zaloga GP, Roberts PR. Early enteral feeding improves outcome. In: Vincent JL, editor. Yearbook of intensive care and emergency medicine. Berlin, Heidelberg: Springer-Verlag, 1997: 701–4Google Scholar
  79. 79.
    Chellis MJ, Sanders SV, Webster H, et al. Early enteral feeding in pediatric intensive care unit. J Parenter Enteral Nutr 1996; 20: 71–3CrossRefGoogle Scholar
  80. 80.
    Fisher GW. Immunoglobulin therapy of neonatal group B streptococcal infections: an overview. Pediatr Infect Dis J 1988; 7(5 Suppl.): S13–6Google Scholar
  81. 81.
    Wolach B. Neonatal sepsis: pathogenesis and supportive therapy. Semin Perinatol 1997; 21(81): 28–38PubMedCrossRefGoogle Scholar
  82. 82.
    Lefering R, Neugebauer EAM. A steroid controversy in sepsis and septic shock: a meta-analysis. Crit Care Med 1995; 23: 1294–308PubMedCrossRefGoogle Scholar
  83. 83.
    Klastersky J, Cappel R, Debusscer L. Effectiveness of betamethasone in management of severe infections. N Engl J Med 1971; 284: 1248–50PubMedCrossRefGoogle Scholar
  84. 84.
    Zeni F, Freeman B, Natanson C. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med 1997; 25: 1115–24CrossRefGoogle Scholar
  85. 85.
    Schumer W. Steroids in the treatment of clinical septic shock. Ann Surg 1976; 184: 333–41PubMedCrossRefGoogle Scholar
  86. 86.
    Schumann RR, Rietschel ET. Endotoxin — structure, recognition, cellular response and septic shock. Antiinfect Drugs Chemother 1995; 13(2): 115–24Google Scholar
  87. 87.
    Natanson C, Esposito CJ, Banks SM. The sirens’ songs of confirmary sepsis trials: selection bias and sampling error. Crit Care Med 1998; 26: 1963–71CrossRefGoogle Scholar
  88. 88.
    Pajkrt D, van Deventer SJH. Immunomodulation of septic shock. Antiinfect Drugs Chemother 1995; 13(2): 125–8Google Scholar
  89. 89.
    Smith JW, Urba WJ, Curti BD, et al. The toxic and hematologic effects of interleukin-1 alpha administered in a phase 1 trial to patients with advanced malignancies. J Clin Oncol 1992; 10: 1141–52PubMedGoogle Scholar
  90. 90.
    Wherry J, Wenzel R, Wunderink R, et al. Monoclonal antibody to tumor necrosis factor (TNF MAb): multicenter efficacy and safety study in patients with sepsis syndrome [abstract 696]. Presented at the 33rd International Conference on Antimicrobial Agents and Chemotherapy, New Orleans; 1993 Oct 17–20. Washington, DC; American Society for Microbiology, 1993; 246Google Scholar
  91. 91.
    Lauterbach R, Pawlik D, Kowalczyk D, et al. Effect of the immunomodulating agent, pentoxifylline, in the treatment of sepsis in prematurely delivered infants: a placebo-controlled, double-blind trial. Crit Care Med 1999; 27(4): 807–14PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  • Niels von Rosenstiel
    • 1
  • Ines von Rosenstiel
    • 2
  • Dieter Adam
    • 1
  1. 1.University Children’s HospitalMunichGermany
  2. 2.Academic Medical Center, Emma Children’s Hospital, Department of Pediatric Intensive CareUniversity of AmsterdamAmsterdamThe Netherlands

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