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

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

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

5. H2OH2O H2OH2O Vascular spaceInterstitial space crystalloid hydrostatic oncotic

6. H2OH2O H2OH2O Vascular spaceInterstitial space hydrostatic oncotic 5% albumin early

7. H2OH2O H2OH2O Vascular spaceInterstitial space hydrostatic oncotic albumin 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 All patients33±2695±42 n=34 Survivors42±26 97±49 n=18 Non survivors23±1894±37 n=16 Colloid9 ml/kg37 ml/kg Carcillo JA JAMA 1991; 266:1242 1 h 6 h mean ± SD mean ± SD P<0.05, mean vol in 1st hr survivors vs nonsurvivors Fluid administered (mls/kg)

10. Fluid Resuscitation in Septic Shock Group 1 (n=14)11±871±29 <20 ml/kg Group 2 (n=11)32±5108±54 20-40 ml/kg Group 3 (n=9)69±19117±29 >40 ml/kg Carcillo JA JAMA 1991; 266:1242 1 h 6 h mean ± SD mean ± SD 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. Septic Shock Myocardial Function in Sepsis

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. Myocardial Function in Sepsis Hours from baselinr 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- 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?

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 MAP (mmHg) 66±268±371±566±3 CI (L/min) 4.1±13.4±0.64.2±1.14±1.1 PVR196±4183±487±1162±12 urine (ml/hr) 36±2238±2227±16104±56 gast PCO2 grad 3.2±2.47.2±1.411.3±5.517.9±6 nor-epinephrine n=4vasopressin n=4 baselinepost inf (4hr)baselinepost inf (4hr) Patel B. Am J Respir Crit Care Med 1998;A608

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

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

28. Steroid Response in Sepsis Annane D JAMA 2000; 283:1038 n=189 cortisol 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

33. Extracorporeal Life Support for Meningococcaemia 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 Goldman AP Lancet 1997; 349:466

34. 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

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

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