Recent Developments in
Management –
MRF, November 2013
Simon Nadel
Pediatr Crit Care Med 2013; 14:686–693
(Pediatr Crit Care Med 2013; 14:686–693)
Pediatr Crit Care Med 2013; 14:686–693

CFR = 8.9% (2005 data)
Lancet 2013; 381: 1224–34
Lancet 2013; 381: 1224–34
Lancet 2013; 381: 1224–34
(Crit Care Med 2013; 41:580–637)
Changes in the revised guidelines
1 Inotropes administered through peripheral or intraosseous line before
central access i...
CHEST 2009; 136:1237–1248

Retrospective survey of 5715 adults with septic shock:
Survival after appropriate antibiotic th...
JAMA. 2010;303(21):2165-2171
(Crit Care Med 2012; 40:3135–3139)

N = 177; 54% mortality
32-34 degrees for 24 hrs

98% had VF or other shockable rhythm
Lancet Neurol 2013; 12: 546–53

77 children cooled to 32-33oC for 48 hrs
JAMA, October 2013

98 adults 32-34oC for 48 hrs
(Crit Care Med 2002; 30:1365–1378)

CHILDREN
• Septic shock always associated with severe
hypovolaemia
• Mortality is asso...
Treatment of shock
• Treat underlying cause
• Rapid intravascular volume expansion
guided by clinical examination and
seri...
91 children with septic shock; 26 died (29% mortality)
Shock reversal in 75 minutes was associated with 96% survival
(OR f...
Emergency management of children with severe sepsis in the
United Kingdom – the results of the Paediatric Intensive Care
S...
Shock
• 139 children were shocked at PICU referral
• No difference in volume of fluid administered after arrival of PICU t...
Which fluid and how much?
• 20ml/kg boluses
• 40 – 60ml/kg in 1st hour (may need huge volumes
(>200ml/kg)
• If no response...
Saline versus Albumin Fluid Evaluation
N Engl J Med. 2011
Jun 30;364:248395.
Mortality within 48 hours of
randomisation
Treatment Group
Albuminbolus

Salinebolus

No
bolus

Total

Total
randomise
d

...
Crit Care Med 2011 Vol. 39, No. 2
Retrospective analysis of 778 patients in a study of vasopressin
CVP > 12mmHg at 12 hrs ...
(Crit Care Med 2012; 40:2883–2889)

• 168 children allocated to liberal/conservative fluids or
fluids not allocated
CHEST 2013; 143(6):1548–
1553
Sites for intervention in sepsis
Antibiotics
Sites for intervention in sepsis
Antibiotics
Anti TLR4
JAMA. 2013;309(11):1154-1162

1961 adults with septic shock: 2:1 Eritoran vs placebo
Sites for intervention in sepsis
Antibiotics
Anti TLR4

CVVH
Intensive Care Med (2013) 39:1535–1546

70 ml/kg/hr vs 35 ml/kg/hr – 138 patients
Sites for intervention in sepsis
Antibiotics
Anti TLR4

CVVH

ART 123
Crit Care Med 2013; 41:2070–2079

• Reduces thrombin-mediated clotting and enhances protein C
activation at the site of cl...
Crit Care Med
2013; 41:2070–
2079
700 patients: median age 1.3 years
75% post cardiac surgery
10% trauma/high risk surgery
4.6% infection
2.3% neurological ...
(Crit Care Med 2013; 41:580–637)
Crit Care Med 2010; 38:367–374

15022 patients
165 sites

37%
30.8%
What can we do?
Thank you!
Round up of new developments in clinical management of meningitis or sepsis in paediatric and adult settings - See more at...
Round up of new developments in clinical management of meningitis or sepsis in paediatric and adult settings - See more at...
Round up of new developments in clinical management of meningitis or sepsis in paediatric and adult settings - See more at...
Round up of new developments in clinical management of meningitis or sepsis in paediatric and adult settings - See more at...
Round up of new developments in clinical management of meningitis or sepsis in paediatric and adult settings - See more at...
Round up of new developments in clinical management of meningitis or sepsis in paediatric and adult settings - See more at...
Round up of new developments in clinical management of meningitis or sepsis in paediatric and adult settings - See more at...
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Round up of new developments in clinical management of meningitis or sepsis in paediatric and adult settings - See more at: http://www.meningitis.org/conference2013#sthash.uhJT7UuZ.dpuf

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Dr Simon Nadel's presentation at Meningitis Research Foundation's 2013 conference, Meningitis & Septicaemia in Children & Adults

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Round up of new developments in clinical management of meningitis or sepsis in paediatric and adult settings - See more at: http://www.meningitis.org/conference2013#sthash.uhJT7UuZ.dpuf

  1. 1. Recent Developments in Management – MRF, November 2013 Simon Nadel
  2. 2. Pediatr Crit Care Med 2013; 14:686–693
  3. 3. (Pediatr Crit Care Med 2013; 14:686–693)
  4. 4. Pediatr Crit Care Med 2013; 14:686–693 CFR = 8.9% (2005 data)
  5. 5. Lancet 2013; 381: 1224–34
  6. 6. Lancet 2013; 381: 1224–34
  7. 7. Lancet 2013; 381: 1224–34
  8. 8. (Crit Care Med 2013; 41:580–637)
  9. 9. Changes in the revised guidelines 1 Inotropes administered through peripheral or intraosseous line before central access is available. • Based on observation that few practitioners in emergency setting able to establish central venous access before 2 hours. • Delayed administration of inotrope associated with 20-fold increased mortality risk (Ninis et al, BMJ 2005). 2 High-flow heated, humidified oxygen be provided by nasal cannula to support respiratory distress until more definitive therapy is available. 3 Although implied in 2002, it is now unequivocally recommended that antibiotics be administered within the first hour.
  10. 10. CHEST 2009; 136:1237–1248 Retrospective survey of 5715 adults with septic shock: Survival after appropriate antibiotic therapy - 52% Survival after inappropriate antibiotic therapy - 10.3%
  11. 11. JAMA. 2010;303(21):2165-2171
  12. 12. (Crit Care Med 2012; 40:3135–3139) N = 177; 54% mortality
  13. 13. 32-34 degrees for 24 hrs 98% had VF or other shockable rhythm
  14. 14. Lancet Neurol 2013; 12: 546–53 77 children cooled to 32-33oC for 48 hrs
  15. 15. JAMA, October 2013 98 adults 32-34oC for 48 hrs
  16. 16. (Crit Care Med 2002; 30:1365–1378) CHILDREN • Septic shock always associated with severe hypovolaemia • Mortality is associated with low cardiac output rather than reduced SVR (c.f. adults)
  17. 17. Treatment of shock • Treat underlying cause • Rapid intravascular volume expansion guided by clinical examination and serial measurement of urine output • In paediatric septic shock rapid fluid resuscitation (40-60 mL/kg in the first hour) is associated with improved survival
  18. 18. 91 children with septic shock; 26 died (29% mortality) Shock reversal in 75 minutes was associated with 96% survival (OR for survival of > 9) Nonsurvivors were treated with more inotropes (dopamine/dobutamine [42% vs 20%]; epinephrine/norepinephrine [42% vs 6%]) but not increased fluid therapy (32.9 mL/kg vs 20.0 mL/kg). (NS) Each additional hour of persistent shock was associated with >2-fold increased odds of mortality
  19. 19. Emergency management of children with severe sepsis in the United Kingdom – the results of the Paediatric Intensive Care Society sepsis audit. David Inwald, Robert Tasker, Mark Peters and Simon Nadel, on behalf of the Paediatric Intensive Care Society Study Group Archives of Diseases in Childhood 2009 May;94(5):348-53 • • • • • • 200 children with sepsis referred to PICU in the UK over a 6 month period (February – July 2008) Median age 13.6 months (IQR 2.9-39.4m) 58% male PIM2 predicted mortality 10% (5-16) 135 (67%) received inotropes 22 (11%) eventually required RRT • 34 (17%) died
  20. 20. Shock • 139 children were shocked at PICU referral • No difference in volume of fluid administered after arrival of PICU team • Those with shock reversal by PICU admission had better outcome vs those where shock was not reversed: • 3/53 (6%) died in the group which reversed shock vs 21/83 (25%) in those who remained shocked (p=0.003). • The only variable independently associated with death in PICU was presence of shock after inter-hospital transfer (p=0.008). • Odds ratio for death in PICU if shock was present at PICU admission was 3.8 (95% CI 1.4-10.2).
  21. 21. Which fluid and how much? • 20ml/kg boluses • 40 – 60ml/kg in 1st hour (may need huge volumes (>200ml/kg) • If no response need I+V, inotropes, invasive monitoring • No increase in risk of ARDS or cerebral oedema • Which fluid should we use?
  22. 22. Saline versus Albumin Fluid Evaluation
  23. 23. N Engl J Med. 2011 Jun 30;364:248395.
  24. 24. Mortality within 48 hours of randomisation Treatment Group Albuminbolus Salinebolus No bolus Total Total randomise d 1050 1047 1044 3141 Total died 111 110 76 297 10.6% 10.5% 7.3% 9.5% % died
  25. 25. Crit Care Med 2011 Vol. 39, No. 2 Retrospective analysis of 778 patients in a study of vasopressin CVP > 12mmHg at 12 hrs associated with greatest risk of death
  26. 26. (Crit Care Med 2012; 40:2883–2889) • 168 children allocated to liberal/conservative fluids or fluids not allocated
  27. 27. CHEST 2013; 143(6):1548– 1553
  28. 28. Sites for intervention in sepsis Antibiotics
  29. 29. Sites for intervention in sepsis Antibiotics Anti TLR4
  30. 30. JAMA. 2013;309(11):1154-1162 1961 adults with septic shock: 2:1 Eritoran vs placebo
  31. 31. Sites for intervention in sepsis Antibiotics Anti TLR4 CVVH
  32. 32. Intensive Care Med (2013) 39:1535–1546 70 ml/kg/hr vs 35 ml/kg/hr – 138 patients
  33. 33. Sites for intervention in sepsis Antibiotics Anti TLR4 CVVH ART 123
  34. 34. Crit Care Med 2013; 41:2070–2079 • Reduces thrombin-mediated clotting and enhances protein C activation at the site of clotting. • Has anti-inflammatory properties • IV injection of ART-123 enhances reversal of DIC and may reduce organ dysfunction and mortality in patients with sepsisassociated DIC • 750 patients randomised
  35. 35. Crit Care Med 2013; 41:2070– 2079
  36. 36. 700 patients: median age 1.3 years 75% post cardiac surgery 10% trauma/high risk surgery 4.6% infection 2.3% neurological disorder Mortality: 5.7 vs 2.6% 2o infection: 37 vs 29%
  37. 37. (Crit Care Med 2013; 41:580–637)
  38. 38. Crit Care Med 2010; 38:367–374 15022 patients 165 sites 37% 30.8%
  39. 39. What can we do?
  40. 40. Thank you!

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