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DOI: 10.1055/s-2005-872507
© Georg Thieme Verlag Stuttgart · New York
Intensivmedizinische Therapie infektiöser Komplikationen in der pädiatrischen Hämatologie und Onkologie
Management of Septic Shock and Acquired Respiratory Distress Syndrome in Pediatric Cancer PatientsPublication History
Publication Date:
15 November 2005 (online)
![](https://www.thieme-connect.de/media/klinpaed/2005S1/lookinside/thumbnails/10.1055-s-2005-872507-1.jpg)
Zusammenfassung
Zum septischen Schock kommt es bei 6 % der pädiatrischen hämatologisch-onkologischen Patienten mit Granulozytopenie und Fieber, mit einer Sepsisletalität von 5 % ohne und 40 % mit Knochemarktransplantation (KMT). Unter allen Kindern mit ARDS leidet ein Drittel an Störungen der Immunkompetenz. Die Letalität beträgt hier ca. 45 %, nach KMT ca. 80 %. Für den septischen Schock sind zu mehr als 75 % gramnegative Keime ursächlich. Das ARDS ist in über 50 % der Fälle Folge von Pneumonien, darunter 20 % durch opportunistische Erreger und einer Sepsis in 25 %. Die vorliegende Arbeit enthält umfassende Empfehlungen der der Arbeitsgruppe „Infektionen bei immunsupprimierten Kindern” der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI) und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) zur Behandlung bei septischen Schock und akutem Lungenversagen. Therapiemaßnahmen beim septischen Schock sind eine frühe Antibiotikatherapie bzw. Elimination des Herdes und die rasche Volumenexpansion (≥ 40 ml/kg in der ersten Stunde). Der Volumenrefraktäre Schock erfordert den Einsatz von Vasopressoren (Noradrenalin), gefolgt von einer differenzierten Kreislauftherapie. Die Substitution von Hydrokortison ist häufig indiziert. Grundpfeiler der ARDS-Behandlung sind die Therapie des Auslösers und eine Beatmung mit ausreichendem endexspiratorischem Druck (PEEP) und begrenzten Tidalvolumen (≤ 6 ml/kg) bzw. limitierten Spitzendrücken (< 35 cmH2O) um eine weitere iatrogene Lungenschädigung zu minimieren. Die Volumentherapie zielt auf eine ausreichende Vorlast, um auch unter Beatmung mit hohem PEEP ein ausreichendes Herzzeitvolumen zu erhalten. Das freie Lungenwasser wird durch Gabe von Diuretika und nötigenfalls eine venovenöse Hämofiltration gesenkt. Die Gabe von Surfactant ist in refraktären Fällen zu erwägen. Steroide sind bei Pneumozystis-Infektionen und beim Engraftment-Syndrom indiziert.
Abstract
Septic shock occurs in 6 % of paediatric cancer patients with neutropenia and fever. The mortality of the septic shock is 40 % in BMT patients and 5 % in others. One third of paediatric ARDS cases affect immunocompromised individuals with a total mortality of 45 % and 80 % after BMT. Septic shock is caused by gram-negative bacteria in more than 75 %. ARDS is due to pneumonia in more than 50 %, sepsis in about 25 %. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for treatment of septic shock and ARDS. Therapy of septic shock includes early antibiotic therapy and volume expansion (≥ 40 ml/kg initially). Refractory shock requires vasopressors (noradrenaline), followed by a judicious circulatory management. Hydrocortison is indicated in patients with high probability of adrenal insufficiency. Mainstay of ARDS therapy is ventilation with sufficient endexspiratory pressure (PEEP) to prevent loss of functional residual capacity and with limited tidal volumes (≤ 6 ml/kg) and limited inspiratory pressure (< 35 cmH2O) respectively, to minimize ventilator induced lung injury. Volume therapy consists of maintenance of sufficient preload to counteract the impaired venous return, induced by positive pressure ventilation. Diuretics and eventually veno-venous haemofiltration are used to reduce free lung water. Surfactant application may be considered in severe cases. Steroids are indicated in pneumocystis carinii pneumonia and in engraftment pneumonitis.
Schlüsselwörter
septischer Schock - ARDS - Immundefizienz
Key words
septic shock - ARDS - immunodeficiency
Literatur
- 1 The Acute Respiratory Distress Syndrome Network . Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000; 342 1301-1308
- 2 Aledo A, Heller G, Ren L. et al . Septicemia and septic shock in pediatric patients: 140 consecutive cases on a pediatric hematology-oncology service. J Pediatr Hematol Oncol. 1998; 20 215-221
- 3 Amato M B, Barbas C S, Medeiros D M. et al . Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998; 338 347-354
- 4 Annane D, Sebille V, Charpentier C. et al . Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. Jama. 2002; 288 862-871
- 5 Arnold J H, Hanson J H, Toro-Figuero L O. et al . Prospective, randomized comparison of high-frequency oscillatory ventilation and conventional mechanical ventilation in pediatric respiratory failure. Crit Care Med. 1994; 22 1530-1539
- 6 Artigas A, Bernard G R, Carlet J. et al . The American-European Consensus Conference on ARDS, part 2. Ventilatory, pharmacologic, supportive therapy, study design strategies and issues related to recovery and remodeling. Intensive Care Med. 1998; 24 378-398
- 7 Asfar P. Terlipressin in chronic hyperdynamic endotoxic shock: is it safe?. Intensive Care Med. 2003; 29 154-155
- 8 Ashbaugh D G, Bigelow D B, Petty T L. et al . Acute respiratory distress in adults. Lancet. 1967; 2 319-323
- 9 Bartlett R H, Roloff D W, Custer J R. et al . Extracorporeal life support: the University of Michigan experience. Jama. 2000; 283 904-908
- 10 Barton P, Garcia J, Kouatli A. et al . Hemodynamic effects of i.v. milrinone lactate in pediatric patients with septic shock. A prospective, double-blinded, randomized, placebo-controlled, interventional study. Chest. 1996; 109 1302-1312
- 11 Bell M, Jackson E, Mi Z. et al . Low-dose theophylline increases urine output in diuretic-dependent critically ill children. Intensive Care Med. 1998; 24 1099-1105
- 12 Bernard G R, Artigas A, Brigham K L. et al . The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994; 149 818-824
- 13 Bernard G R, Luce J M, Sprung C L. et al . High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med. 1987; 317 1565-1570
- 14 Bernard G R, Vincent J L, Laterre P F. et al . Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001; 344 699-709
- 15 Bienkowski R S, Gotkin M G. Control of collagen deposition in mammalian lung. Proc Soc Exp Biol Med. 1995; 209 118-140
- 16 Bindl L, Buderus S, Dahlem P. et al . Gender-based differences in children with sepsis and ARDS: the ESPNIC ARDS Database Group. Intensive Care Med. 2003; 29 1770-1773
- 17 Bindl L, Dresbach K, Lentze M J. Incidence of acute respiratory distress syndrome in German children and adolescents: a population-based study. Crit Care Med. 2005; 33 209-312
- 18 Boldt J, Heesen M, Welters I. et al . Does the type of volume therapy influence endothelial-related coagulation in the critically ill?. Br J Anaesth. 1995; 75 740-746
- 19 Booy R, Habibi P, Nadel S. et al . Reduction in case fatality rate from meningococcal disease associated with improved healthcare delivery. Arch Dis Child. 2001; 85 386-390
- 20 Briegel J, Forst H, Haller M. et al . Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med. 1999; 27 723-732
- 21 Brochard L, Roudot-Thoraval F, Roupie E. et al . Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS. Am J Respir Crit Care Med. 1998; 158 1831-1838
- 22 Brower R G, Shanholtz C B, Fessler H E. et al . Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med. 1999; 27 1492-1498
- 23 Brun-Buisson C, Minelli C, Bertolini G. et al . Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study. Intensive Care Med. 2004; 30 51-61
- 24 Bunchman T E, Maxvold N J, Barnett J. et al . Pediatric hemofiltration: Normocarb dialysate solution with citrate anticoagulation. Pediatr Nephrol. 2002; 17 150-154
- 25 Capizzi S A, Kumar S, Huneke N E. et al . Peri-engraftment respiratory distress syndrome during autologous hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001; 27 1299-1303
- 26 Carcillo J A. Pediatric septic shock and multiple organ failure. Crit Care Clin. 2003; 19 413-440
- 27 Carcillo J A, Fields A I. Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. Crit Care Med. 2002; 30 1365-1378
- 28 Ceneviva G, Paschall J A, Maffei F. et al . Hemodynamic support in fluid-refractory pediatric septic shock. Pediatrics. 1998; 102 e 19
- 29 Chittock D R, Dhingra V K, Ronco J J. et al . Severity of illness and risk of death associated with pulmonary artery catheter use. Crit Care Med. 2004; 32 911-915
- 30 Cooper D J, Walley K R, Wiggs B R. et al . Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study. Ann Intern Med. 1990; 112 492-498
- 31 de Kleijn E D, de Groot R, Hack C E. et al . Activation of protein C following infusion of protein C concentrate in children with severe meningococcal sepsis and purpura fulminans: a randomized, double-blinded, placebo-controlled, dose-finding study. Crit Care Med. 2003; 31 1839-1847
- 32 Dellinger R P, Carlet J M, Masur H. et al . Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2004; 30 536-555
- 33 Dellinger R P, Zimmerman J L, Taylor R W. et al . Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med. 1998; 26 15-23
- 34 DiCarlo J V, Alexander S R, Agarwal R. et al . Continuous veno-venous hemofiltration may improve survival from acute respiratory distress syndrome after bone marrow transplantation or chemotherapy. J Pediatr Hematol Oncol. 2003; 25 801-805
- 35 Dobyns E L, Cornfield D N, Anas N G. et al . Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure. J Pediatr. 1999; 134 406-412
- 36 Finfer S, Bellomo R, Boyce N. et al . A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004; 350 2247-2256
- 37 Gattinoni L, Tognoni G, Pesenti A. et al . Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med. 2001; 345 568-573
- 38 Greenhalgh D G, Warden G D. The importance of intra-abdominal pressure measurements in burned children. J Trauma. 1994; 36 685-690
- 39 Gregory T J, Steinberg K P, Spragg R. et al . Bovine surfactant therapy for patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 1997; 155 1309-1315
- 40 Hallahan A R, Shaw P J, Rowell G. et al . Improved outcomes of children with malignancy admitted to a pediatric intensive care unit. Crit Care Med. 2000; 28 3718-3721
- 41 Han Y Y, Sun W Z. An evidence-based review on the use of corticosteroids in peri-operative and critical care. Acta Anaesthesiol Sin. 2002; 40 71-79
- 42 Hilbert G, Gruson D, Vargas F. et al . Noninvasive continuous positive airway pressure in neutropenic patients with acute respiratory failure requiring intensive care unit admission. Crit Care Med. 2000; 28 3185-3190
- 43 Jacobe S J, Hassan A, Veys P. et al . Outcome of children requiring admission to an intensive care unit after bone marrow transplantation. Crit Care Med. 2003; 31 1299-1305
- 44 Kellum J A, Angus D C, Johnson J P. et al . Continuous versus intermittent renal replacement therapy: a meta-analysis. Intensive Care Med. 2002; 28 29-37
- 45 Kornecki A, Frndova H, Coates A L. et al . A randomized trial of prolonged prone positioning in children with acute respiratory failure. Chest. 2001; 119 211-218
- 46 Kühl P, Appel R, Lasch P. et al . ARDS im Kindesalter. Ergebnisse einer Umfrage an Deutschen Kinderkliniken und Empfehlungen der „Arbeitsgemeinschaft ARDS im Kindesalter” zur Beatmungstherapie. Monatsschr Kinderheilkd. 1996; 144 1110-1116
- 47 Larche J, Azoulay E, Fieux F. et al . Improved survival of critically ill cancer patients with septic shock. Intensive Care Med. 2003; 29 1688-1695
- 48 Lundin S, Mang H, Smithies M. et al . Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide. Intensive Care Med. 1999; 25 911-919
- 49 Martin G S, Mangialardi R J, Wheeler A P. et al . Albumin and furosemide therapy in hypoproteinemic patients with acute lung injury. Crit Care Med. 2002; 30 2175-2182
- 50 McGowan S E. Extracellular matrix and the regulation of lung development and repair. Faseb J. 1992; 6 2895-2904
- 51 Meduri G U, Headley A S, Golden E. et al . Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. Jama. 1998; 280 159-165
- 52 Moller J C, Schaible T, Roll C. et al . Treatment with bovine surfactant in severe acute respiratory distress syndrome in children: a randomized multicenter study. Intensive Care Med. 2003; 29 437-446
- 53 O'Brien A, Clapp L, Singer M. Terlipressin for norepinephrine-resistant septic shock. Lancet. 2002; 359 1209-1210
- 54 Ognibene F P, Martin S E, Parker M M. et al . Adult respiratory distress syndrome in patients with severe neutropenia. N Engl J Med. 1986; 315 547-551
- 55 Outwater K M, Treves S T, Lang P. et al . Renal and hemodynamic effects of dopamine in infants following cardiac surgery. J Clin Anesth. 1990; 2 253-257
- 56 Pathan N, Hemingway C A, Alizadeh A A. et al . Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock. Lancet. 2004; 363 203-209
- 57 Pesenti A. Target blood gases during ARDS ventilatory management. Intensive Care Med. 1990; 16 349-351
- 58 Peters M J, Booth R A, Petros A J. Terlipressin bolus induces systemic vasoconstriction in septic shock. Pediatr Crit Care Med. 2004; 5 112-115
- 59 Pollard A J, Britto J, Nadel S. et al . Emergency management of meningococcal disease. Arch Dis Child. 1999; 80 290-296
- 60 Putensen C, Mutz N J, Putensen-Himmer G. et al . Spontaneous breathing during ventilatory support improves ventilation-perfusion distributions in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 1999; 159 1241-1248
- 61 Ranieri V M, Suter P M, Tortorella C. et al . Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. Jama. 1999; 282 54-61
- 62 Ringe H I, Varnholt V, Gaedicke G. Cardiac rescue with enoximone in volume and catecholamine refractory septic shock. Pediatr Crit Care Med. 2003; 4 471-475
- 63 Rivers E, Nguyen B, Havstad S. et al . Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001; 345 1368-1377
- 64 Rommelsheim K, Lackner K, Westhofen P. et al . Respiratory distress syndrome of the adult in the computer tomograph. Anasth Intensivther Notfallmed. 1983; 18 59-64
- 65 Rossi R, Shemie S D, Calderwood S. Prognosis of pediatric bone marrow transplant recipients requiring mechanical ventilation. Crit Care Med. 1999; 27 1181-1186
- 66 Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomised trials. Bmj. 1998; 316 961-964
- 67 Stewart T E, Meade M O, Cook D J. et al . Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group. N Engl J Med. 1998; 338 355-361
- 68 Stuber F, Wrigge H, Schroeder S. et al . Kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury. Intensive Care Med. 2002; 28 834-841
- 69 Sumarmo. The role of steroids in dengue shock syndrome. Southeast Asian J Trop Med Public Health. 1987; 18 383-389
- 70 Suter P M. MV causes lung inflammation and systemic immune depression. A balance of fire and ice. Intensive Care Med. 2002; 28 383-385
- 71 Suter P M, Fairley B, Isenberg M D. Optimum end-expiratory airway pressure in patients with acute pulmonary failure. N Engl J Med. 1975; 292 284-289
- 72 Takahashi Y, Kobayashi Y, Chikayama S. et al . Effect of granulocyte/colony-stimulating factor on the onset of the adult respiratory distress syndrome. Acta Haematol. 1999; 101 124-129
- 73 Taylor R W, Zimmerman J L, Dellinger R P. et al . Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial. Jama. 2004; 291 1603-1609
- 74 Tomaske M, Bosk A, Eyrich M. et al . Risks of mortality in children admitted to the paediatric intensive care unit after haematopoietic stem cell transplantation. Br J Haematol. 2003; 121 886-891
- 75 den Berghe G van, Wouters P, Weekers F. et al . Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001; 345 1359-1367
- 76 Watson R S, Carcillo J A, Linde-Zwirble W T. et al . The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med. 2003; 167 695-701
- 77 Westphal M, Bone H G, Aken H Van. et al . Terlipressin for haemodynamic support in septic patients: a double-edged sword?. Lancet. 2002; 360 1250-1251
- 78 Willson D F, Thomas N J, Markovitz B P. et al . Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial. Jama. 2005; 293 470-476
PD Dr. Lutz Bindl
Klinik f. Kinderkardiologie · RWTH Aachen
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