Paediatric Sepsis

1:15am: 3 year old female arrives at Triage with HR 180, RR 35, looks tired. Has had URTI symptoms for past couple of days.

1:25am: ICU/Paeds Reg called by ED doctor saying can you come and have a look

1:35am:You make your first assessment HR 180

Quiet, tired, opens eyes

Mod respiratory distress

Cap refill 4 seconds

WHAT DO YOU DO?

Why are we worried about it?

Still remains significant cause of morbidity and mortality

5-30% of paediatric patients with sepsis will develop septic shock

Mortality rates in septic shock are 20-30% (up to 50% in some countries)

Recognition

Most people dont recognise shock

Resuscitation must be done in a proactive time-sensitive manner

Every minute counts golden hour

Every hour without appropriate resuscitation and restoration of blood pressure increases mortality risk by 40%

How do we define it

Systemic Inflammatory Response Syndrome

Infection

Sepsis

Severe Sepsis

Septic Shock

Systemic Inflammatory Response Syndrome

Presence of 2 of the following criteria:

Core Temp >38.5 or < 36 degrees

Mean HR > 2SD for age or persistent elevation over 0.5-4hrs

If < 1yr old: bradycardia HR < 10th centile for age

Mean RR > 2 SD above normal for age

Leucocyte abnormality

SEPSIS

SIRS in presence of suspected or proven infection

Severe Sepsis

Sepsis + one of the following CV organ dysfunction

ARDS

2 or more organ dysfunction

Septic Shock

Sepsis + CV organ dysfunction

Cardiovascular dysfunction

Despite >40ml/kg Isotonic fluid bolus in 1 hour: Decrease in BP 5 seconds

Core-peripheral temp gap >3 degrees

Risk factors for Sepsis in Children

< 1 year of age

Very low birthweight infants

Prematurity

Presence of underlying illness eg chronic lung, cardiac conditions, malignancy

Co-morbidities

Boys

Genetic factors

What makes you suspect shock?

Clinical Manifestations

Fever

Increased HR

Increased RR

Altered mental state

Skin: Hypoperfusion

Decreased capillary refill

Petechiae, purpura

Cool vs warm.

Cold Shock Warm Shock

HR Tachycardia Tachycardia

Peripheries Cool Warm

Pulses Difficult to palpate Bounding

Skin Mottled, pale Flushed

Capillary refill Prolonged Blushing

Mental state Altered Altered

Urine Oliguria Oliguria

Blood Pressure in Children

This is main difference with adults.

Blood pressure does not fall in septic shock until very late.

CO= HR x SV

HR in children much higher therefore BP falling is late.

Pulse pressure is often useful

Normal: Diastolic BP > systolic BP.

Investigations

Basic bloods:

CBC, EUC, LFT, CMP, Coags, Glucose

Inflammatory markers: PCT, CRP

Acid- Base status

Venous or arterial blood gas:

Lactate

Base deficit

Investigations

Septic Work up

Urine, blood, sputum cultures

Viral cultures: throat, NPA, faeces,

Never do CSF in shocked patient

Imaging:

CXR, CT, MRI, PET scan, ECHO, Ultrasound

MANAGEMENT

General Principles

Early Recognition

Early and appropriate antimicrobials

Early and aggressive therapy to restore balance between oxygen delivery and demand

Early and goal directed therapy

What is Goal Directed Therapy?

Based on studies in adults initially Use fluid resuscitation, vasoactive infusions,

oxygen to aim to restore balance between oxygen delivery and demand

Goals: Capillary refill < 2 seconds Urine ouptut > 1ml/kg/hr Normal pulses Improved mental state Decreased lactate and base deficits Perfusion pressures appropriate for age

Recognise decreased mental status and perfusionMaintain airway and establish access

Push 20mls/kg isotonic saline or colloid boluses up to and over

60mls/kg

Antimicrobials, Correct hypoglycemia and hypocalemia

Fluid Responsiveness Fluid Refractory shock

O min

5 min

15 min

Observe in PICU

Recognise decreased mental status and perfusionMaintain airway and establish access

Vascular Access: Only few minutes to be spent on obtaining IV access Need to use IO if cant get access May need to put 2 x IO in

Intubation + Ventilation Clinical assessment of work of breathing , hypoventilation or impaired

mental state Up to 40% of cardiac output is used for work of breathing Volume loading and inotrope support is recommended before and during

intubation Recommended: Ketamine, atropine and short acting neuromuscular

blocking agent.

Push 20mls/kg isotonic saline or colloid boluses up to and over

60mls/kg

Antimicrobials, Correct hypoglycemia and hypocalemia

Fluid Resuscitation: Needs to be given as push May need to give up to 200mls/kg Give fluid until perfusion improves.

Which Fluids Isotonic vs collloid Most evidence extrapolated from adults Wills et al

RCT of cystalloid vs colloid in children with dengue fever No difference between the two groups.

Fluid Refractory Shock15min

Begin dopamine or peripheral adrenaline

Establish central venous access

Establish arterial access

Titrate Adrenaline for cold shock and noradrenaline for

warm shock to normal MAP-CVP and SVC sats>70%

Catecholamine resistant shock 60 min

Catecholamine Resistant Shock

At Risk of adrenal insufficency give hydrocortisone

Not at Risk - dont give hydrocortisone

Normal Blood Pressure

Cold Shock

SVC < 70%

Low Blood Pressure

Cold Shock

SVC < 70%

Low Blood

Pressure

Warm Shock

Add vasodilator or

Type III PDE inhibitor

Titrate volume and

adrenalineTitrate volume &

Noradrenaline

Consider

Vasopressin

ECMO

Drug Dose Comments

Dopamine 2-20mcg/kg/min Historically 1st choice in kids

Alpha, beta and dopamine receptor

activation

Can be given peripherally

Dobutamine 5-10mcg/kg/min Chronotropic as well as inotropic

Afterload reduction

Adrenaline 0.05- 1mcg/kg/min Initially increases contractility/heart

rate

High doses increase PVR

Noradrenaline 0.05 1 mcg/kg/min

Vasopressor

Increases PVR

Milrinone 0.25-

0.75mcg/kg/min

Phosphodiesterase inhibitor

Afterload reduction

Rivers et al, NEJM 2001 Single Centre , RCT in Emergency Department Goal directed vs standard care in septic adults in

first 6 hours in ED Goal directed therapy consisted of

CVP 8-12mmHg MAP > 65mmHg Urine output >0.5ml/kg/hour ScVO2 > 70%

Showed significant decrease in mortality Cristisms: control group had higher mortality rate

and benefits may be because group was monitored more closely

Ceneviva et al, Pediatrics 1998

Single centre, 50 children

Used goal directed therapy : CI 3.3-6Lmin/m2 in children with fluid refractory shock

Mortality from sepsis decreased by 18% when compared to 1985 study

De Oliveira ICM 2008

RCT , single centre

Use of 2002 guidelines with continous central venous O2 saturation monitoring and therapy directed to maintain ScVO2 > 70%

Mortality decreased from 39% to 12 %,

Number needed to treat 3.6

Brierley and Carcillo CCM 2009

Update of 2002 guidelines for goal directed therapy

Look at all studies who had adopted 2002 guidelines and their success.

Reported studies that showed decrease in mortality with adoption of 2002 guidelines.

New changes : Inotrope via peripheral access

Fluid removal considered early

What about Hydrocortisone?

Controversial

Rational is that there is hypothalamic-pituitary adrenal axis dyfunction in patients with septic shock

Current recommendations: If child is at risk of adrenal insufficency and remains in

shock should receive hydrocortisone

At risk defined as purpura fulminans, congenital adrenal hyperplasia, recent steroid exposure, hypothalamic/pituitary abnormality

Evidence Controversial

Annane D JAMA 2002 Multicentre , RCT looked at use of hydrocortisone and

fludrocortisone in septic shock.

Corticus Trial, NEJM 2008 Mutlicentre, RCT

Hydrocortisone vs placebo in septic shock

No significant difference in mortality

Many criticisms Inadequate power

Selection bias

Evidence- paediatrics

No RCT in paediatric patients with sepsis

Markovitz : PCCM 2005

Retrospective cohort study , 6000 paediatric patients

Systemic steriods associated with increased mortality

But no control in place for severity of illness or for dose.

Other treatment

Maintain Glucose control

Nutrition

Maintain Hb > 10g/dL

GI protection

Early CVVH

Activated Protein C

Inhibits factors Va and VIIIa prevent generation of thrombin

Decreased inflammation through inhibition of platelet activation, neutrophil recruitment

Initially had popularity as possible treatment option in septic shock

Concern with it is risk of serious haemorrhage

RESOLVE Study, Lancet 2007

RCT, multicentre, international study in 477 children with severe sepsis.

Compared APC to placebo for 96 hrs

Primary end point: time to complete organ failure resolution

Study stopped early as interim analysis showed no benefit

More bleeding in APC group but not significantly different

ECMO

Study published this month from RCH Melbourne

Looked at ECMO use in paediatric septic shock

96% had at least 3 organ failure and 35% had a cardiac arrest prior to ECMO

23 patients with refractory septic shock received central ECMO

17 (74%) patients survived to be discharged from hospital.