non-dialytic therapy for sepsis in the paediatric patient desmond bohn the department of critical...
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Non-Dialytic Therapy for Sepsis in the Paediatric Patient
Desmond BohnThe Department of Critical Care MedicineThe hospital for Sick Children, Toronto
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Shock
Inadequate tissue oxygen delivery
Multi-organ failure
Death
Vascular failure Cardiac failure
Hypovolaemia
Sepsis
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Albumin leak and vascular permeabilityFleck A Lancet 1985; 1:781
Albumin transcapillary escape rate
16 patients post CPB
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H2O
Vascular space Interstitial space
Reduced Inravascular volume
hydrostatic
oncotic H2O
shock
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H2O
H2O
Vascular space Interstitial space
crystalloid
hydrostatic
oncotic
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H2O
H2O
Vascular space Interstitial space
hydrostatic
oncotic
5% albumin
early
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H2O
H2O
Vascular space Interstitial space
hydrostatic
oncotic
albumin
late
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Fluid Resuscitation in Septic ShockCarcillo 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
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Fluid Resuscitation in Septic Shock
All patients 33±26 95±42n=34
Survivors 42±26‡ 97±49n=18
Non survivors 23±18 94±37n=16
Colloid 9 ml/kg 37 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)
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Fluid Resuscitation in Septic Shock
Group 1 (n=14) 11±8 71±29<20 ml/kg
Group 2 (n=11) 32±5 108±5420-40 ml/kg
Group 3 (n=9) 69±19 117±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 mmHg24% patients were hypovolaemic at 6 h
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0
2
4
6
8
10
12
14
16
group 1 group 2 group 3 groups 1 & 2
no. o
f pat
ient
s
survivors
deaths
Fluid Resuscitation in Septic ShockCarcillo 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
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0
2
4
6
810
12
14
16
18
ARDS No ARDS
No.
of
pati
ents
survivors
deaths
Fluid Resuscitation in Septic ShockCarcillo JA JAMA 1991; 266:1242
Group 1 <20 ml/kg
Group 2 20-40 m/kg
Group 3 >40 ml/kg
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Myocardial Function in SepsisMercier J-C Crit Care Med 1988; 16:27
Haemodynamic patterns of meningococcal shock in children
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Septic ShockMyocardial Function in Sepsis
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Myocardial Function and SepsisQuezado ZMN Am J Kid Dis
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Myocardial Function in SepsisParillo JE J Clin Invest 1985; 76:1539
Circulating myocardial depressant substance in septic shock
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Myocardial Function in Sepsis
Hours from baselinrHours from baselinr
Suffredini AF N Engl J Med 1989; 321:280
Endotoxin administration in normal humans
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Myocardial Function in SepsisOgnibene FP Chest 1988; 93: 903
Response to volume infusion in sepsis
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Myocardial Function and SepsisPagani FD J Clin Invest 1992; 90:389
Effect of TNF-on LV function
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Myocardial Function and SepsisFinkel MS Science 1992; 257:387
Negative inotropic effect of cytokines mediated by NO
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Haemodynamic support in sepsis
Pressor or inotrope?
Pressor or inotrope?
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Norepinephrine and Septic ShockMartin C Crit Care Med 2000; 28:2758
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Vasopressin in vasodilatory septic shockTsuneyoshi I Crit Care Med 2001; 29:487
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Vasopressin in Septic ShockPatel 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
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Vasopressin in Septic Shock
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
nor-epinephrine n=4 vasopressin n=4baseline post inf (4hr) baseline post inf (4hr)
Patel B. Am J Respir Crit Care Med 1998;A608
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Rivers E N Engl J Med 2001; 345:1368
Early goal-directed therapy in the treatment of severe sepsis and septic shock
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Rivers E N Engl J Med 2001; 345:1368
Early goal-directed therapy in the treatment of severe sepsis and septic shock
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Steroid Response in SepsisAnnane D JAMA 2000; 283:1038
n=189
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%
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Stress dose steroids in hyperdynamic septic shock
Briegel J Crit Care Med 1999; 27:723
RCT40 patients randomised100 mg loading dose followed by 0.18 mg/kg/hr
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Activated protein C in SepsisBernard GR New Engl J Med 2001; 344:699
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Activated protein C in SepsisBernard GR New Engl J Med 2001; 344:699
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Extracorporeal Life Support for Meningococcaemia
•12 patients with meningococcaemia7 with refractory shock5 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
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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
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Stress dose steroids in hyperdynamic septic shock
Briegel J Crit Care Med 1999; 27:723
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Myocardial Function in SepsisParillo JE J Clin Invest 1985; 761539
Circulating myocardial depressant substance in sepsis