Debate on aggressive vs restricted fluid resuscitation in childhood sepsis
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Transcript of Debate on aggressive vs restricted fluid resuscitation in childhood sepsis
Meningococcal disease
Fluid resuscitation in meningococcal sepsis :less or more
Michael Levin
Debate MRF conference 2013© Imperial College London
© Imperial College London
© Imperial College London
Where did this protocol come from?
Is it evidence based ?
Physiological basis vs Evidence from Randomised Trials
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© Imperial College London
What is the evidence for hypovolaemia?
• CVP and echocardiography suggests volume depletion pre fluid resuscitation
• Capillary leak
Microvascular Events in Sepsis
© Imperial College London
© Imperial College London© Imperial College London
Fra
c tio
nal c
l ea r
ance
of
al b
u mi n
x 1
0-5
Controls Mild Moderate Severe Fatal Nephrotics
Meningococcal Disease
Orogui critical care med 1999
Protein leak in meningococcal sepsis
What are the consequences of volume replacemeent if there is a generalised capillary leak
• Pulmonary Oedema• Cerebral Oedema• Tissue oedema and ascites• Compartment synbdrome
© Im
peria
l Col
lege
Lon
don
© Imperial College London
A delicate balance:
Fluids restore ventricular filling
Capillary leak may lead to pulmonary oedema; tissue oedema
Early elective ventilation
Early dialysis / haemofiltration
What is the role of cardiac failure
• Impaired myocardial contractility• Inotrope unresponsiveness• Pulmonary oedema following volume
resuscitation
Capillary Leak
Reduced circulating volume
Reduced preload
Acidosis
Hypoxia
Hypoglycaemia
Hypocalcaemia
Hypokalaemia
HypophosphataemiaTNF, IL1
Nitric oxide complement Hypotension
Reduced coronary perfusion
Cardiodepressant factors
Bacterial toxins
Neutrophil products
PAF
Prostaglandins
Energy depletion
Myocardial Failure
© Imperial College London
© Im
peria
l Col
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Lon
don
Role of IL6 in myocardial depression in meningococcal septic shockPathan et al Lancet 2004
© Imperial College London
De
ath
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%)
Ad
mis
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ns
40
30
20
10
0
100
80
60
40
20
0
predicted death rate (%)
1992 1993 1994 1995 1996 1997
Admissions & mortality from severemeningococcal disease, St Mary’s PICU, 1992-97
observeddeath rate (%)
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If Fluid reuscitation improves outcome in sepsis in PICU, would it improve outcome of sepsis/Malaria in Africa ?
Highest rates of child mortality are in Africa1 in 8 children dies before age 5 (20-fold the mortality in industrialized countries)
15-30% mortality among children admitted to hospitals in sub-Saharan Africadespite being on antibiotics and quinine>50% deaths occur within 24 hours of admissionsupportive therapies often not considered/unavailable
FEAST Trial Fluid Expansion As Supportive Therapy in critically ill African children
Fluid Expansion As a Supportive TherapyFluid Expansion As a Supportive Therapy
malaria
consortium
Disease Control, Better Health www.malariaconsortium.org
FEAST Trial Team (PI Prof Kath Maitland)
Fluid Expansion As a Supportive TherapyFluid Expansion As a Supportive Therapy
21
KENYAKilifi
TANZANIATeule
UGANDA (4 centres)Mulago Hospial, KampalaMbale SorotiLacor Hospital, Gulu
UNITED KINGDOM
MRC Clinical Trials Unit, London&Imperial College, London (Sponsor)
Albumin and Saline donated by Baxter,
Funded by MRC, UK
FEAST partners
Support:
Trial Design: EARLY fluid resuscitation (FEAST A)
Children with impaired consciousness and/or
respiratory distress and impaired perfusion
Bolus 5% albumin
20 ml/Kg (40 ml/Kg after Aug 2010) over 1
hour
Bolus 0.9% saline
20 ml/Kg (40 ml/Kg after Aug 2010) over 1 hour
Control (No bolus)
Maintenance fluids only
Children with respiratory distress and clinical evidence of impaired
perfusion
Follow-up to 4 weeks (24 weeks if developed neurological sequelae by 4 weeks)Clinical assessments at 1, 4, 8, 24, 48 hours and at 4 weeks
Impaired perfusionAny one of: • Cap refill 3 or more
secs, • Severe tachycardia, • temperature gradient• weak pulse
Excluded: Fluid loss due to gastroenteritis, burns or trauma. Severe malnutrition
Children with febrile illness and impaired perfusion with impaired consciousness and/or respiratory distress
Hypotensive Shock (FEAST Stratum B)
Children eligible for FEAST A that have hypotensive shock* on admission
Bolus 5% albumin
40mls/kg (60mls/kg after August 2010) per hour
Bolus 0.9% saline
40mls/kg (60mls/kg after August 2010) per hour
Follow-up to 4 weeks (24 weeks if developed neurological sequelae by 4 weeks)Clinical assessments at 1, 4, 8, 24, 48 hours and at 4 weeks
*Hypotensive shock defined as severe hypotension plus signs of impaired perfusion. Severe hypotension: <1yr sbp <50mmHg; 1-5 yrs sbp <60mmHg; >5yrs: sbp <70mmHg
Typical setting of the trial
FEAST(Fluid Expansion As Supportive Therapy) Trial
0%
85%
90%
95%
100%P
erce
nt
surv
ived
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48
Hours from admission
No Bolus 92.7%Boluses89.4%
FEAST: Survival in first 48 hours
3.3% excess mortality in bolus arms (10.6%) vs control (7.3%)No difference in mortality between Albumin vs saline boluses
Response to the trial
Should FEAST result in changes to UK meningococcal sepsis algorhythm ??
• Why did Fluids cause Harm in FEAST• Are the findings applicable to Developed countries• How does availability of ventilation;inotropes; PICU
alter findings from FEAST
• All subgroups showed harm in FEAST• Anemia/non anemic; acidosis/non acidosis; malaria/non
malaria
A personal perspective
• FEAST should not be ignored by developed country PICUs
• Fluids may have caused pulmonary deterioration or cerebral oedema
• The broad inclusion criteria might have resulted in patients with pneumonia and heart failure being included.
• The availability of ventilation and inotropes may mitigate the pulmonary / cardiac/ cerebral effects of fluids
• BUT it is the only RCT of fluids with a control arm
Fluid resuscitation in septic shock: between Sylla and Charybdis
Protocolised management is good
But thought may be better
Fluid bolus may be life saving in severe shock BUT may be associated with pulmonary and cerebral oedema
Fluids should be used with more thought; and continual re evaluation to detect adverse effects
Less may be more- and we need further studies- Including further analysis of FEAST Data which should be open access
© Imperial College London
Thank you
© Imperial College London