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

**

www.wfpiccs.org