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)

CFR = 8.9% (2005 data)

Pediatr Crit Care Med 2013; 14:686–693

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 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.

Retrospective survey of 5715 adults with septic shock:

Survival after appropriate antibiotic therapy - 52%

Survival after inappropriate antibiotic therapy - 10.3%

CHEST 2009; 136:1237–1248

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

(Crit Care Med 2012; 40:3135–3139)

N = 177; 54% mortality

98% had VF or other shockable rhythm

32-34 degrees for 24 hrs

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

CHILDREN• Septic shock always associated with severe

hypovolaemia

• Mortality is associated with low cardiac output

rather than reduced SVR (c.f. adults)

(Crit Care Med 2002; 30:1365–1378)

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

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

• 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

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

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).

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?

Saline versus Albumin Fluid Evaluation

N Engl J Med. 2011 Jun 30;364:2483-95.

Mortality within 48 hours of randomisation

  Treatment Group  

 Albumin-

bolusSaline-bolus

No bolus Total

Total randomised 1050 1047 1044 3141

Total died 111 110 76 297

% died 10.6% 10.5% 7.3% 9.5%

Retrospective analysis of 778 patients in a study of vasopressin

CVP > 12mmHg at 12 hrs associated with greatest risk of death

Crit Care Med 2011 Vol. 39, No. 2

(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 sepsisAntibiotics

Sites for intervention in sepsisAntibiotics

Anti TLR4

JAMA. 2013;309(11):1154-1162

1961 adults with septic shock: 2:1 Eritoran vs placebo

Sites for intervention in sepsisAntibiotics

CVVH

Anti TLR4

Intensive Care Med (2013) 39:1535–1546

70 ml/kg/hr vs 35 ml/kg/hr – 138 patients

Sites for intervention in sepsisAntibiotics

CVVH

Anti TLR4

ART 123

• 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 sepsis-associated DIC

• 750 patients randomised

Crit Care Med 2013; 41:2070–2079

Crit Care Med 2013; 41:2070–2079

700 patients: median age 1.3 years75% post cardiac surgery10% trauma/high risk surgery4.6% infection2.3% neurological disorder

Mortality: 5.7 vs 2.6%

2o infection: 37 vs 29%

(Crit Care Med 2013; 41:580–637)

Crit Care Med 2010; 38:367–374

15022 patients165 sites

37%

30.8%

What can we do?

Thank you!