Are the SSC Guidelines helpful in children?
Joseph A Carcillo MDUniversity of Pittsburgh
Pittsburgh, PA, USA
The distribution of global child mortality
1 dot = 5000 annual deaths
Black RE, Morris SS, Bryce J. Lancet 2003;361:2226-2234
WHO (2006)• Top killers of children
– Pneumonia– Diarrheal Diseases– Neonatal sepsis– Perinatal asphyxia– Malaria– Measles– 80% of deaths can be classified as sepsis
deaths
Feasibility and Effectiveness of Home-based Management for Neonatal Sepsis
VHW’s to diagnose sepsis using clinical algorithms and treat at home.(Gadchiroli, India, 1996 – 2003)
Villages = 39Neonates = 5268 (93%)
Bang AT et al: J Perinatal. 2005; 25:S62-S71
Interventions for Home Management
• Health education of family for danger signs call• VHW’s monitoring and recording of s/s• VHW’s diagnose sepsis if 2 or more s/s• For sepsis
– Inform parents– Advise – hospital or home treatment– Gentamicin IM and co-trimoxazole PO x 7 days– Daily visits – if no improvement in 24 hours hospital– Record outcome
Bang AT et al: J Perinatal. 2005; 25:S62-S71
Outcomes
Case Fatality:Treated(7%) vs Untreated (22%)
• Preterm home-based Rx – 67% reduction
• Low birth weight 72% reduction
Bang AT et al: J Perinatal. 2005; 25:S62-S71
Effect of HBC on IMR
Bang AT J Perinatol 2005;25: S92- S107
Zinc Supplementation- Trial ProfileRandomized control trial Zinc (70 mg weekly) in low income families in Bangladesh
Brooks WA Lancet 2005;366:999-1004
Zinc Supplements on Pneumonia and Diarrhoea in Children <2 yrs
• Pneumonia less (199 vs 286 RR .83, 95%CI .73 - .95)
• Diarrhoea less (1881 vs 2407 RR .94, 95%CI .88 - .99)
• Total Deaths 2 vs 14, p= .013• Pneumonia Deaths 0 vs 10, p=.013
Brooks WA. Lancet 2005; 366:999-1004
Angkor hospital for Children – Cambodia Pagnarith et al
Pneumonia Mortality
00
05
10
15
20
25
30
35
40#
of P
atie
nts
2005 2006
Figure 2c: Pneumonia Mortality. For all patients with pneumonia presenting to the PICU at AHC in 2006 versus 2005, Odds Ratio for mortality was 0.27 with a 95% C.I. (0.14-0.51) after implementation of bundle.
Pneumonia
0%5%
10%15%20%
25%30%
Intubation Mortality
2005 2006
Figure 2a: The O.R. with 95% C.I. for intubation and mortality is 0.47 (0.26-0.85) and 0.27 (0.14-0.51) respectively afte rimplementtaion of bundle.
Isolated Pneumonia
0%
5%
10%
15%
20%
25%
Intubation Mortality
2005 2006
Figure 2b: The O.R. with 95% C.I. for intubation and mortality is 0.48 (0.23-0.99) and 0.19 (0.08-0.44) respectively.
Carcillo JA, Tasker RC. Intensive Care Med 2006;32:958-961
Early reversal of hemodynamic abnormalities reduced mortality (OR 0.44 95% CI [0.29-0.68])
0.00%
5.00%
10.00%
15.00%
20.00%
25.00%
30.00%
35.00%
HR BP CR>2 BP/CR>2
PersistentResolved
2.7%4.5%
7.7%
2.9%
7.6%
12.4%
33.6%
15.8%
(6/298)(40/890)
(16/206)
(4/139)
(5/66)
(36/290)
(80/238)
(3/19)
* *
*
*
Fluid during Malaria Resuscitation
• 150 children with severe falciparum malaria and metabolic acidosis, randomized to receive either 4.5% albumin or NS– Primary outcome = resolution of metabolic
acidosis– Secondary outcome = mortality
• No difference in the primary outcome• Mortality albumin gp. 3.6% (3 of 56) vs. 18% (11 of 61) [95%
CI 1.2-24.8]Maitland K et al. Randomized trial of volume expansion with albuMaitland K et al. Randomized trial of volume expansion with albumin or saline in children with severe min or saline in children with severe
malaria: preliminary evidence of albumin benefit. CIP 2005;40:5malaria: preliminary evidence of albumin benefit. CIP 2005;40:53838--4545
Albumin resuscitation improved outcome in malaria septic shock
0102030405060708090
100
Albumin LR
SNS
Maitland K et al Clin Infect Dis 2005;40: 538
Fluid during Dengue ResuscitationWillis BA et al. Comparison of three fluid solutions for resuscitation in dengue shock syndrome.
NEJM 2005;353:877-89
• Double blinded RCT comparison of 3 fluids for initial resuscitation of children with Dengue fever– 383 children with moderately severe shock received either
RL; 6% dextran 70; 6% HES– 129 children with severe shock received one of the colloids– Primary outcome: requirement for rescue colloid at any time – Only one death– Primary outcome similar
• Conclusion: RL is as effective during the initial resuscitation of shock as these 2 colloids
Wills et al NEJM 2005
Antibiotic coverage
Kumar A et al. Crit Care Med 2006;34:1589Kumar A et al. Crit Care Med 2006;34:1589--15961596
Oral glycerol reduces mortality and neurological morbidity (Clin Inf Dis 2007)
• Oral glycerol reduced mortality/neurological morbidity two fold (OR -.46) compared to Dexamethasone
• Inexpensive, accessible in all parts of the world.
Patients survive surgical sepsis when source is removed (Barie et al 2004)
0%10%20%30%40%50%60%70%80%90%
100%
Inadequate Indeterminate Adequate
Survival
SVCO2 saturation > 70% directed therapy reduces mortality
Rivers (adults) Oliveira (children)
05
1015202530354045
Standard EGDT Standard EGDT
*
*
10-fold reduction in mortality with early goal directed resuscitation
Booy R et al, Arch Dis Child 2001
Best Outcomes after use of Guidelines
• Rotterdam group reports reduction in mortality in severe sepsis and purpura from 20% to 1%
• Pittsburgh group reports 3% mortality in previously healthy and 9% in chronic illness septic shock
0%5%
10%15%20%
Before After
Mortality
0%
5%
10%
PH CI
Mortality
High Flux CRRT for Refractory Shock and Positive Fluid Balance
• CRRT is associated with improved outcome when used before > 10% fluid overload in MOF patients Foland JA Crit Care Med 2004
• MOF and thrombocytopenia have acquired ADAMTS-13 deficiency and may benefit from plasmapheresis Nguyen TC Haematologica, 2007.
• Diuretics and Peritoneal Dialysis effective in fluid overloaded Dengue shock patients
Ranjit et al PCCM 2005
www.wfpiccs.org
Immunizations, Potable Water, Nutrition Zinc,Vitamin A
IM Antibiotics available to All through HCW
1st Hr IV Fluids and Antibiotics O2 / np CPAP
Available in Emergency Clinic
A
B
C
1st Hr IV AntibioticsFluid Resuscitation
Inotrope infusionMechanical Ventilation
Available to All (PICU)
DExtra
CorporealSupport
TRANSPORT
Rotterdam and St Mary’s Report 1-2% mortality withMeningococcal Septic Shockwith 1st hour resuscitation andtransport (was 20-22%)
Sao Paolo reports reductionin mortality from 40% to 12%In Septic Shock with ScvO2Guided to 70% with fluid,Inotropes, pRBCs
Thailand reports60% drop inmortality withNP high flow O2for Pneumonia
Kenya reports 4% mortality with Malaria,
Vietnam reports 0 -1%mortality with
Dengue Shockwith IV fluid
resuscitation(was 24-60%)
Gandchiroli,India reduced neonatal mortality from 16% to 2% with HCW + IM Abx
Bundles A-DA Child mortality > 30 / 1,000B Child mortality < 30 / 1,000 C Developing nationD Developed nation
GLOBAL NEWBORN AND CHILD SEPSIS INITIATIVE
Infections in the Vanguard Phase
• E. Coli• Enterobacter• Klebsiella• S. Pneumococcus• Meningococcus• Staph Aureus • Candida• RSV
• Gram Negative n = 70• Gram Positive n =
120• Mixed n = 32• Fungal n = 8• Viral n = 35
Clinical Results in Vanguard Phase
A B C D
Patients 34 12 84 231
Mortality 30% 17% 30% 11%
Neurological Morbidity
16% 10% 11.9% 2.0%
Other Morbidity
5.9% 8.3% 6.8% 1.0%
Clinical Results
0%
5%
10%
15%
20%
25%
30%
Mortality Neuro Other
ABCD
Comparison of Resource Specific Bundle Compliance
C D
Gender 50% female 42% female
Age 51.12+/- 51.94 74.68+/- 77.91
Compliant Resuscitation
23.8% 51.8%
Compliant Management
9.5% 25.1%
Mortality 30% 11.5%
Reduced mortality with Bundle Compliance in combined C + D
00.10.20.30.40.50.60.70.80.9
1
Resuscitation Bundle Management Bundle
CompliantNon-Compliant
**
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