Non-Dialytic Therapy for Sepsis in the Paediatric Patient

Desmond BohnThe Department of Critical Care MedicineThe hospital for Sick Children, Toronto

Shock

Inadequate tissue oxygen delivery

Multi-organ failure

Death

Vascular failure Cardiac failure

Hypovolaemia

Sepsis

Albumin leak and vascular permeabilityFleck A Lancet 1985; 1:781

Albumin transcapillary escape rate

16 patients post CPB

H2O

Vascular space Interstitial space

Reduced Inravascular volume

hydrostatic

oncotic H2O

shock

H2O

H2O

Vascular space Interstitial space

crystalloid

hydrostatic

oncotic

H2O

H2O

Vascular space Interstitial space

hydrostatic

oncotic

5% albumin

early

H2O

H2O

Vascular space Interstitial space

hydrostatic

oncotic

albumin

late

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

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)

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

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

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

Myocardial Function in SepsisMercier J-C Crit Care Med 1988; 16:27

Haemodynamic patterns of meningococcal shock in children

Septic ShockMyocardial Function in Sepsis

Myocardial Function and SepsisQuezado ZMN Am J Kid Dis

Myocardial Function in SepsisParillo JE J Clin Invest 1985; 76:1539

Circulating myocardial depressant substance in septic shock

Myocardial Function in Sepsis

Hours from baselinrHours from baselinr

Suffredini AF N Engl J Med 1989; 321:280

Endotoxin administration in normal humans

Myocardial Function in SepsisOgnibene FP Chest 1988; 93: 903

Response to volume infusion in sepsis

Myocardial Function and SepsisPagani FD J Clin Invest 1992; 90:389

Effect of TNF-on LV function

Myocardial Function and SepsisFinkel MS Science 1992; 257:387

Negative inotropic effect of cytokines mediated by NO

Haemodynamic support in sepsis

Pressor or inotrope?

Pressor or inotrope?

Norepinephrine and Septic ShockMartin C Crit Care Med 2000; 28:2758

Vasopressin in vasodilatory septic shockTsuneyoshi I Crit Care Med 2001; 29:487

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

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

Rivers E N Engl J Med 2001; 345:1368

Early goal-directed therapy in the treatment of severe sepsis and septic shock

Rivers E N Engl J Med 2001; 345:1368

Early goal-directed therapy in the treatment of severe sepsis and septic shock

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%

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

Activated protein C in SepsisBernard GR New Engl J Med 2001; 344:699

Activated protein C in SepsisBernard GR New Engl J Med 2001; 344:699

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

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

Stress dose steroids in hyperdynamic septic shock

Briegel J Crit Care Med 1999; 27:723

Myocardial Function in SepsisParillo JE J Clin Invest 1985; 761539

Circulating myocardial depressant substance in sepsis