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Non-Dialytic Therapy for Sepsis in the Paediatric Patient

Non-Dialytic Therapy for Sepsis in the Paediatric Patient. Desmond Bohn The Department of Critical Care Medicine The hospital for Sick Children, Toronto. Sepsis. Vascular failure. Cardiac failure. Hypovolaemia. Shock. Inadequate tissue oxygen delivery. Multi-organ failure. Death.

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Non-Dialytic Therapy for Sepsis in the Paediatric Patient

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  1. Non-Dialytic Therapy for Sepsis in the Paediatric Patient Desmond Bohn The Department of Critical Care Medicine The hospital for Sick Children, Toronto

  2. Sepsis Vascular failure Cardiac failure Hypovolaemia Shock Inadequate tissue oxygen delivery Multi-organ failure Death

  3. Albumin leak and vascular permeability Fleck A Lancet 1985; 1:781 Albumin transcapillary escape rate 16 patients post CPB

  4. Reduced Inravascular volume Vascular space Interstitial space oncotic H2O shock H2O hydrostatic

  5. Vascular space Interstitial space oncotic H2O crystalloid hydrostatic H2O

  6. Vascular space Interstitial space oncotic H2O 5% albumin hydrostatic H2O early

  7. Vascular space Interstitial space oncotic H2O albumin H2O hydrostatic late

  8. Fluid Resuscitation in Septic Shock Carcillo JA JAMA 1991; 266:1242 • Effects of early fluid resuscitation in paediatric septic shock • Patients septic shock & PA catheter at 6 hrs • Mortality and morbidity endpoints • ARDS defined by bilateral infiltrates, hypoxaemia & PCWP <15 mmHg

  9. Fluid Resuscitation in Septic Shock Carcillo JA JAMA 1991; 266:1242 1 h 6 h mean ± SD mean ± SD All patients 33±26 95±42 n=34 Survivors 42±26‡ 97±49 n=18 Non survivors 23±18 94±37 n=16 Colloid 9 ml/kg 37 ml/kg Fluid administered (mls/kg) ‡ P<0.05, mean vol in 1st hr survivors vs nonsurvivors

  10. Fluid Resuscitation in Septic Shock Carcillo JA JAMA 1991; 266:1242 1 h 6 h mean ± SD mean ± SD Group 1 (n=14) 11±8 71±29 <20 ml/kg Group 2 (n=11) 32±5 108±54 20-40 ml/kg Group 3 (n=9) 69±19 117±29 >40 ml/kg Mean PCWP at 6 h was 11.5 mmHg 24% patients were hypovolaemic at 6 h

  11. Fluid Resuscitation in Septic Shock Carcillo JA JAMA 1991; 266:1242 Group 1 <20 ml/kg Group 2 20-40 m/kg Group 3 >40 ml/kg * *Significant difference in survival between group 3 and groups 1 & 2 individually and combined

  12. Fluid Resuscitation in Septic Shock Carcillo JA JAMA 1991; 266:1242 Group 1 <20 ml/kg Group 2 20-40 m/kg Group 3 >40 ml/kg

  13. Myocardial Function in Sepsis Mercier J-C Crit Care Med 1988; 16:27 Haemodynamic patterns of meningococcal shock in children

  14. Myocardial Function in Sepsis Septic Shock

  15. Myocardial Function and Sepsis Quezado ZMN Am J Kid Dis

  16. Myocardial Function in Sepsis Parillo JE J Clin Invest 1985; 76:1539 Circulating myocardial depressant substance in septic shock

  17. Hours from baselinr Hours from baselinr Myocardial Function in Sepsis Suffredini AF N Engl J Med 1989; 321:280 Endotoxin administration in normal humans

  18. Myocardial Function in Sepsis Ognibene FP Chest 1988; 93: 903 Response to volume infusion in sepsis

  19. Myocardial Function and Sepsis Pagani FD J Clin Invest 1992; 90:389 Effect of TNF-a on LV function

  20. Myocardial Function and Sepsis Finkel MS Science 1992; 257:387 Negative inotropic effect of cytokines mediated by NO

  21. Haemodynamic support in sepsis Pressor or inotrope? Pressor or inotrope?

  22. Norepinephrine and Septic Shock Martin C Crit Care Med 2000; 28:2758

  23. Vasopressin in vasodilatory septic shock Tsuneyoshi I Crit Care Med 2001; 29:487

  24. Vasopressin in Septic Shock Patel B. Am J Respir Crit Care Med 1998;A608 • A randomised blinded study • Patients with SIRS requiring pressor support • Fluid resuscitated • Randomised to nor-epinephrine or vasopressin

  25. Vasopressin in Septic Shock Patel B. Am J Respir Crit Care Med 1998;A608 nor-epinephrine n=4 vasopressin n=4 baseline post inf (4hr) baseline post inf (4hr) MAP (mmHg) 66±2 68±3 71±5 66±3 CI (L/min) 4.1±1 3.4±0.6 4.2±1.1 4±1.1 PVR 196±4 183±4 87±11 62±12 urine (ml/hr) 36±22 38±22 27±16 104±56 gast PCO2 grad 3.2±2.4 7.2±1.4 11.3±5.5 17.9±6

  26. Early goal-directed therapy in the treatment of severe sepsis and septic shock Rivers E N Engl J Med 2001; 345:1368

  27. Early goal-directed therapy in the treatment of severe sepsis and septic shock Rivers E N Engl J Med 2001; 345:1368

  28. Steroid Response in Sepsis n=189 Annane D JAMA 2000; 283:1038 cortisol <34 ug/dl and delta > 9 ug/dl mort 26% cortisol 34 ug/dl and delta <9 ug/dl mort 67% cortisol >34 ug/dl and delta >9 ug/dl cortisol < 34 ug/dl and delta <9 ug/dl mort 82%

  29. Stress dose steroids in hyperdynamic septic shock Briegel J Crit Care Med 1999; 27:723 RCT 40 patients randomised 100 mg loading dose followed by 0.18 mg/kg/hr

  30. Activated protein C in Sepsis Bernard GR New Engl J Med 2001; 344:699

  31. Activated protein C in Sepsis Bernard GR New Engl J Med 2001; 344:699

  32. Extracorporeal Life Support for Meningococcaemia Goldman AP Lancet 1997; 349:466 • 12 patients with meningococcaemia • 7 with refractory shock • 5 with severe ARDS • Age 4 mths to 18 yrs (median 26 mths) • Median duration of support was 76 (20-263) hrs • 9 survivors

  33. Summary Sepsis characterised by hypovolaemia, vasculopathy and decreased myocardial function Therapy should be focused on strategies that maximise tissue oxygen delivery Anti-cytokine therapies have so far proven ineffective Steroids and APC may improve the outcome in severe sepsis

  34. Stress dose steroids in hyperdynamic septic shock Briegel J Crit Care Med 1999; 27:723

  35. Myocardial Function in Sepsis Parillo JE J Clin Invest 1985; 761539 Circulating myocardial depressant substance in sepsis

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