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Emergency Department Paediatric Septic Shock- towards early goal directed therapy Elliot Long Paediatric Acute Care 2011 Conference

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Page 1: Paediatric Septic Shock - towards early goal …...15% not given dopa/ dobu despite fluid refractory shock • 23% not given catechol for dopa/ dobu refractory shock • 30% not given

Emergency Department

Paediatric Septic Shock- towards early goal directed therapy

Elliot Long Paediatric Acute Care 2011

Conference

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Emergency Department

Outline Rivers Protocol (EGDT)

ACCM Sepsis Protocol

• Evidence

Barriers to implementation

Future considerations

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Emergency Department

EGDT Rivers Protocol

• Adult study of 263 patients in septic shock • Compared “standard care” with targeted care (CVP,

MAP, Hb, ScvO2) over first 6 hours • Reduction in mortality from 46.5% to 30.5% • EGDT group received more fluid in first 6 hours (no

difference at 72 hours) more PRBC and more inotr • First study to show that EARLY and TARGETED

therapy in septic shock improves outcome

Rivers et al NEJM Nov 2001

Presenter
Presentation Notes
ScvO2- SVC; SvO2- PA
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Emergency Department

Page 5: Paediatric Septic Shock - towards early goal …...15% not given dopa/ dobu despite fluid refractory shock • 23% not given catechol for dopa/ dobu refractory shock • 30% not given

Emergency Department

Concerns re: • Adequacy of CVP as a marker of volume responsive low cardiac

output

• Liberal fluid resuscitation a risk factor for ALI/ ARDS? • No difference rate of early intubation between EGDT and

control, fewer late intubation in EGDT

• High transfusion rate (64% vs 19% in control)- ? Risk for nosocomial infection, ALI, mortality

• Low ScvO2 (49%), high mortality (46.5%) in control group

Presenter
Presentation Notes
As static value CVP not helpful, if no change after fluid challenge then pt is likely volume responsive (has venous capacitance)- so delta CVP may be useful. Other studies have failed to reproduce such low ScvO2 (median more typically ~74%) or such high mortality (chart)
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Emergency Department

Schmidt Chest 2010

Presenter
Presentation Notes
Control group mortality from ~15 sepsis studies show that mortality correlates well with APACHE 2 score. EGDT trial is an outlier (much higher mortality in control group than expected by APACHE 2 score). Should single centre results that have not been reproduced elsewhere change clinical practice?
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Emergency Department

Insufficient validation reflected in current studies:

• ARISE- Australasian Resuscitation in Sepsis Evaluation n=1600

• ProCESS- Protocolized Care for Early Septic Shock n=1935

• ProMISe- Protocolised Management of Sepsis n=1260

Presenter
Presentation Notes
ProCESS- Pitsburg; ProMISe- UK
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Emergency Department

Rivers protocol applicable to Paediatrics? Central line often not inserted during initial

resuscitation- CVP, ScvO2 unknown Optimal Hb in paediatric septic shock unknown Pathophysiology of sepsis different in children-

myocardial dysfunction more common than vasomotor dysfunction

Showed early and goal directed resuscitation improved survival in adult septic shock- what goals should be targetted in paediatrics?

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Emergency Department

Update 2002 practice parameter • Based on “best clinical practice” and expert opinion

Incorporates evidence for • Validity, efficacy of 2002 guideline • New treatment and outcome studies

Brierly Crit Care Med 2009

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Emergency Department

Emphasis First Hour (ED) Fluid/ inotrope

therapy targeting HR, BP, CR, conscious state

Subsequent (ICU) Haemodynamic

support targeting ScvO2 >70%, CI 3.3-6.0 L/Min/m2

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Emergency Department

Changes Advocate initiation of inotropes peripherally (not

vasopressors) Ketamine for invasive procedures (etomidate

discouraged) CO measurement with doppler echo, pulse index

contour, FA thermodilution (vs PA catheter) Rescue therapies (levosimendan) Early fluid removal following resuscitation

Presenter
Presentation Notes
Etomidate- risk of adrenal suppression. Rescue therapies for recalcitrant cardiogenic shock (inodolator therapy).
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Emergency Department

Presenter
Presentation Notes
American College of Critical Care Medicine Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock
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Emergency Department

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Emergency Department

Presenter
Presentation Notes
Physiology of fluid resuscitation
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Emergency Department Evidence for early aggressive fluid resuscitation

34 patients correlating volume of fluid administered at 1 and 6 hours with survival • Group 1 (<20ml/kg) - 11ml/kg at 1 hour and 71ml/kg at

6 hours (43% survived) • Group 2 (20-40ml/kg) - 32ml/kg at 1 hour and 108ml/kg

at 6 hours (36% survived) • Group 3 (>40ml/kg) - 69ml/kg at 1 hour and 117ml/kg

at 6 hours (89% survived)

No increased risk of ARDS with more volume

Carcillo JAMA 1991

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Emergency Department

Similar total volume of fluid administered at 6 hours in groups 2 and 3, suggesting that EARLY administration improves survival

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Emergency Department

Retrospective transport database review over 9 year period

91 paediatric patients with clinical septic shock Shock reversal = normal SBP and CR 9-fold improved odds of survival with early shock

reversal (PRISM adjusted) Every hour of ongoing shock associated with 2x

increased risk mortality (PRISM adjusted) Initial resuscitation greatest impact on survival

Han Pediatrics 2003

Presenter
Presentation Notes
Study from CHOP. Shock reversal defined as normalisation of CR and SBP. Early (median 75min) successful shock reversal assoc with survival 96%. Nonsurvivors treated with more inotrope and less fluid than survivors (median 20 vs 32 ml/kg). Early resuscitation improves survival similar finding to Rivers (different therapeutic end-points).
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Emergency Department

Early aggressive fluid resuscitation improves survival

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Emergency Department

How much fluid to administer PALS/ ACCM- “until rales or hepatomegaly

develop” Other methods of volume assessment

• Clinical (HR, CR, LOC, u/o) • CVP • Passive leg raise / hepatic palpation • Arterial pulse pressure variation • IVC ultrasound • echo

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Emergency Department

What Fluid- crystaloid vs colloid 17 studies, 1977

participants Albumin reduced risk of

mortality in sepsis

(pooled OR 0.82 95% CI 0.67-1.0 p=0.47)

Delaney Crit Care Med 2011

Presenter
Presentation Notes
Paediatric studies included showed a decrease in mortality using colloid, but were in patients with dengue haemorrhagic fever and malaria. Another consideration is cost- 1L crystaloid costs ~$1.50, 1L 5% albumin costs ~$70.
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Emergency Department

Colloid may improve survival (but is more expensive)

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Emergency Department

Evidence for early antibiotic administration Retrospective adult cohort

study, 2154 patients Survival 80% with

adequate antimicrobial administration within 1 hour of hypotension

Each hour delay associated with an increased risk of mortality of 7.6%

Kumar Crit Care Med 2006

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Emergency Department

Early antibiotics improve survival

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Emergency Department

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Emergency Department

Presenter
Presentation Notes
Sepsis is a spectrum of disease and can change in nature during treatment. CVAD related sepsis more likely to be warm shock, community acquired sepsis more likely to be cold shock (Peters Ped 2008).
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Emergency Department

Inotrope

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Emergency Department

Which inotrope to use Recommendations (grade 2C):

• Initial: dopamine • For cold shock: epinepherine • For warm shock: norepinepherine

Special circumstances: • Low CO/ high SVR: dobutamine / phosphodiesterase

inhibitor • Low SVR despite norepinepherine: vasopressin (NB-

trend towards incr mortality in Choong Am J Resp Crit Care Med 2009)

Presenter
Presentation Notes
NB- dopamine in adults associated with increased risk of death compared with noradrenaline.
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Emergency Department

Systemic Vascular Resistance

Stroke Volum

e

inotrope

vasodilator

Poor cardiac function

Normal cardiac function

Presenter
Presentation Notes
As SVR increases, stroke volume and thus CO falls for the same MAP (recall MAP ~ SVR x CO). This is the rationale for inodilator therapy.
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Emergency Department

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Emergency Department

Steroids in sepsis 300 adult patients in septic shock Randomised to long course (7 days) of low dose

(50mg q6) hydrocortisone 28 day mortality in patients unresponsive to

corticotropin stimulation test 63% placebo 53% steroid

No mortality difference in responders

Annane JAMA 2002

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Emergency Department

CORTICUS Hydrocortisone therapy

for adult patients in septic shock

N = 499 47.6% had no response to

corticotropin Hydrocortisone did not

improve survival or reversal of shock (even in non-responders to corticotropin)

NEJM 2007

Presenter
Presentation Notes
All patients received hydrocortisone (50mg q6) or placebo for 5 days AND got a corticotropin stim test (no response to corticotropin implies primary or secondary adrenal insufficiency). Steroids did reduce the time to shock reversal, but were associated with increased risk of superinfection.
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Emergency Department

No benefit overall • Mortality benefit from low dose long course steroid

Problem- heterogeneity of dosing regimes

Increased risk of hyperglycaemia

Annane 2010

Presenter
Presentation Notes
Low dose = 50mg q6 x 7 days.
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Emergency Department

Higher incidence of adrenal insufficiency in children? 78 children with

vasopressor dependent shock

Absolute adrenal insufficiency 56%

Reduced inotrope requirement post steroid supplementation

Impact on mortality unreported

Hebar Crit Care Med 2011

Presenter
Presentation Notes
Different patient population from CORTICUS- more unwell (vasopressor dependent), unknown impact on mortality. CORTICUS also showed short term improvement in clinical condition- shock improved more quickly, but a higher incidence of superinfection, including sepsis and septic shock. Not good evidence supporting the use of steroids even with negative corticotropin test. Absolute adren insuff defined as basal cortisol <18 mg/L.
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Emergency Department

No evidence for survival benefit from steroids in septic shock

Potential benefit from low dose / long

course steroids in corticotropin stimulation non-responders

Presenter
Presentation Notes
In previously healthy children (not at risk of adrenal insufficiency- eg prev steroid use). NB- dosing ranges vary hugely- from 2 to 50mg/kg hydrocortisone (stress vs shock dose).
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Emergency Department

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Emergency Department

Therapeutic end points ScvO2 (SfvO2 adequate?)

Lactate

Lactate clearance

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Emergency Department

ScvO2 vs SfvO2 N=39 Mean ScvO2 73.1% Mean SfvO2 69.1 > 50% diverged > 5%

SfvO2 does NOT correlate well with ScvO2

Davidson Chest 2010

Presenter
Presentation Notes
Lactate does correlate well
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Emergency Department

Should ScvO2 > 70% be a target for resuscitation 102 children in septic shock randomised to

ScvO2 directed therapy or not 28 day mortality 11.8% in directed group, 39.2%

in control group More crystaloid,

blood, inotropic support in ScvO2 directed group

Oliveira Int Care Med 2008

Presenter
Presentation Notes
ScvO2 mean 78% treatment gr, 74% in control. Lactate mean 1.2 treatment gr, 1.1 in control. Lactate not reported in ScvO2 < 70% group. Note similarities with Rivers study! High mortality in control group.
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Emergency Department

Mortality difference more marked in ScvO2 <70% subgroup

Utility in discriminating high risk patients

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Emergency Department

Lactate clearance as a therapeutic target 300 adult patients with septic shock randomised

to ScvO2 targeted care or lactate clearance tergeted care

Mortality targeting ScvO2 > 70%: 23% Mortality targeting lactate clearance >10%: 17%

Lactate clearance is a valid therapeutic end-point

Jones JAMA 2010

Presenter
Presentation Notes
Non-inferiority trial. Lactate clearance defined as >10% on 2 consecutive samples taken >2hrs apart. NB- lactate in adults used to screen for occult sepsis in normotensive patients. Alactaemic sepsis carries risk of mortality.
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Emergency Department

What is optimal Hb In stable patients resuscitated from septic shock:

Hb > 70

In unstable patients being actively resuscitated:

Hb > 100

Karam PCCM 2011 TRIPICU 2007

Presenter
Presentation Notes
No evidence regarding optimal Hb in unstable patients with septic shock
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Emergency Department

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Emergency Department

Retrospective case series 45 patients on VA ECMO for septic shock (40%

cardiac arrest prior to cannulation) 21 (47%) survived to hospital discharge Central cannulation associated with improved

survival (73% vs 44%) None had severe disability on long term follow-

up

Maclaren PCCM 2007

Presenter
Presentation Notes
Central cannulation – (atrioaortic vs IVC-ICA); may have more role in children than adults (myocardial dysfunction more common); allows higher flow, more invasive.
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Emergency Department

Summary of ACCM guideline Early, aggressive fluid resuscitation (consider colloid) Early antibiotics Therapeutic end-points: ScvO2 or lactate/ lactate

clearance

Hb >100 ? benefit from low dose long course steroids Inotrope: dopamine then epinepherine for cold shock and

norepinepherine for warm shock

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Emergency Department

Audit of 17 PICU’s 107 patients with septic shock 8% received care c/w ACCM guideline

• 21% not given >60ml/kg despite ongoing shock • 15% not given dopa/ dobu despite fluid refractory

shock • 23% not given catechol for dopa/ dobu refractory shock • 30% not given steroid despite catechol resistant shock

Inwald Arch Dis Child 2009

Presenter
Presentation Notes
How good are we at implementing ACCM guidelines. C/W ACCM guideline NOT timeline! Replicated in other setting including surviving sepsis campaign audit’s.
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Emergency Department

Why is implementation so poor? Cognitive barriers

• Is severe sepsis seen as a problem • Has there been adequate dissemination of guideline • Are goals of ACCM guideline achievable • Are we practicing “informed skepticism”

Process barriers • Shock recognition • Systems barriers

Presenter
Presentation Notes
As individuals we see severe sepsis rarely. Is guideline available at patient interface to help direct care? Is sepsis so heterogenous a disease that it doesn’t lend itself to protocolisation.
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Emergency Department

Lack of recognition of early shock

Lack of adequate vascular access

Shortage of health care providers • 2 nurses for 15 (25) patients in ED, 2 for 13 in PICU

Non-use of goals and treatment protocols

Oliviera PEC 2008

Presenter
Presentation Notes
Most are surmountable barriers (except lack of health care workers!). Lack of access- did not allow rapid fluid administration.
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Emergency Department

Future Directions Institutional audit Triage tool for early shock recognition Early senior staff review Tiered approach- non-invasive and invasive

clinical pathways Collaboration / frequent review

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Emergency Department

Implementation of sepsis protocol in ED • Triage sepsis recognition tool • Improved staffing of resuscitation area • Prioritisation of antibiotic • Improved graphic vital sign monitoring

Decreased time to first bolus (56 to 22 min) Decreased time to antibiotic administration (130

to 38 min)

Cruz Pediatr 2011

Presenter
Presentation Notes
Collaboration btwn ICU and ED.
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Emergency Department

Questions?

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Emergency Department

Impact of FEAST Mortality after fluid bolus in African Children with severe

infection (n=3141) • Mortality 10.5% with fluid bolus, 7.3% in standard

maintenance fluid group Issues:

• Patient selection • 57% malaria parasitaemia, 32% Hb <50 • 83% respiratory distress, 25% SaO2 <90%

• Diagnosis of shock • One of: severe tachycardia, CR > 3 sec, LL temp

gradient, weak rad pulse volume

Maitland NEJM 2011

Presenter
Presentation Notes
Figure: 48 hour mortality. WHO shock def’n: cold hands, CR > 3 sec, AND weak, fast pulse. Each individual sign has poor specificity for hypovolaemic shock.
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Emergency Department

Treating the wrong children with fluid bolus’ will cause harm

Results of the FEAST Trial should not lead to a change in current practice of fluid bolus administration for septic shock