paediatric sepsis
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Paediatric Sepsis
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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?
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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)
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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%
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How do we define it
• Systemic Inflammatory Response Syndrome
• Infection
• Sepsis
• Severe Sepsis
• Septic Shock
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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
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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
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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
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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
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What makes you suspect shock?
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Clinical Manifestations
• Fever
• Increased HR
• Increased RR
• Altered mental state
• Skin: – Hypoperfusion
– Decreased capillary refill
– Petechiae, purpura
– Cool vs warm.
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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
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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.
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Investigations
• Basic bloods:
– CBC, EUC, LFT, CMP, Coags, Glucose
• Inflammatory markers: PCT, CRP
• Acid- Base status
– Venous or arterial blood gas:
• Lactate
• Base deficit
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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
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MANAGEMENT
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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
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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
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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
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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.
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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.
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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.
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Other treatment
• Maintain Glucose control
• Nutrition
• Maintain Hb > 10g/dL
• GI protection
• Early CVVH
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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
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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
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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.