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

1. Recent Developments in
Management –
MRF, November 2013
Simon Nadel

2. Pediatr Crit Care Med 2013; 14:686–693

3. (Pediatr Crit Care Med 2013; 14:686–693)

4. Pediatr Crit Care Med 2013; 14:686–693
CFR = 8.9% (2005 data)

5. Lancet 2013; 381: 1224–34

6. Lancet 2013; 381: 1224–34

7. Lancet 2013; 381: 1224–34

10. (Crit Care Med 2013; 41:580–637)

12. 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.

13. 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%

15. JAMA. 2010;303(21):2165-2171

16. (Crit Care Med 2012; 40:3135–3139)
N = 177; 54% mortality

17. 32-34 degrees for 24 hrs
98% had VF or other shockable rhythm

18. Lancet Neurol 2013; 12: 546–53
77 children cooled to 32-33oC for 48 hrs

19. JAMA, October 2013
98 adults 32-34oC for 48 hrs

21. (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)

22. 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

23. 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

24. 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

25. 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).

26. 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?

27. Saline versus Albumin Fluid Evaluation

29. N Engl J Med. 2011
Jun 30;364:248395.

30. 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

31. 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

32. (Crit Care Med 2012; 40:2883–2889)
• 168 children allocated to liberal/conservative fluids or
fluids not allocated

33. CHEST 2013; 143(6):1548–
1553

34. Sites for intervention in sepsis
Antibiotics

35. Sites for intervention in sepsis
Antibiotics
Anti TLR4

36. JAMA. 2013;309(11):1154-1162
1961 adults with septic shock: 2:1 Eritoran vs placebo

37. Sites for intervention in sepsis
Antibiotics
Anti TLR4
CVVH

38. Intensive Care Med (2013) 39:1535–1546
70 ml/kg/hr vs 35 ml/kg/hr – 138 patients

39. Sites for intervention in sepsis
Antibiotics
Anti TLR4
CVVH
ART 123

40. 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

41. Crit Care Med
2013; 41:2070–
2079

42. 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%

43. (Crit Care Med 2013; 41:580–637)

44. Crit Care Med 2010; 38:367–374
15022 patients
165 sites
37%
30.8%

46. What can we do?

47. Thank you!