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 don’t 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 <5th centile for age

– Need for vasoactive drug to maintain BP

– 2 of the following: • Unexplained metabolic acidosis

• Increase lactate

• Oliguria

• Prolonged cap refill > 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 > ½ 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 perfusion Maintain 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 perfusion Maintain 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 Shock 15min

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 - don’t 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

adrenaline Titrate 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.