1. Paediatric Septic Shock
Corrine Balit

2. 135am:You make your first assessment
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
135am:You make your first assessment
HR 180
Quiet, tired, opens eyes
Mod respiratory distress
Cap refill 4 seconds
WHAT DO YOU DO?

3. 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).

4. 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%

5. How do we define it Systemic Inflammatory Response Syndrome Infection
Sepsis
Severe Sepsis
Septic Shock

6. Systemic Inflammatory Response Syndrome
Presence of 2 of the following criteria:
Core Temp >38.5 or < 36 degrees
Mean HR > 2SD for age or persitant elevation over hrs
If < 1yr old: bradycardia HR < 10th centile for age
Mean RR > 2 SD above normal for age
Leucocyte abnormality

7. SEPSIS Severe Sepsis Septic Shock
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

8. 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

9. 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

10. What makes you suspect shock?

11. Clinical Manifestations
Fever
Increased HR
Increased RR
Altered mental state
Skin:
Hypoperfusion
Decreased capillary refill
Petechiae, purpura
Cool vs warm.

12. Cold Shock
Warm Shock HR
Tachycardia
Peripheries
Cool
Warm
Pulses
Difficult to palpate
Bounding
Skin
Mottled, pale
Flushed
Capillary refill
Prolonged
Blushing
Mental state
Altered
Urine
Oliguria

13. 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.

14. Investigations Basic bloods: FBC, EUC, LFT, CMP, Coags, Glucose
Inflammatory markers: PCT, CRP
Acid- Base status
Venous or arterial blood gas:
Lactate
Base deficit

15. 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

16. Management

17. 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

18. 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

19. Recognise decreased mental status and perfusion
Maintain airway and establish access
O min
Push 20mls/kg isotonic saline or colloid boluses up to and over 60mls/kg
Antimicrobials, Correct hypoglycemia and hypocalemia
5 min
15 min
Fluid Responsiveness
Fluid Refractory shock
Observe in PICU

20. 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.

21. Antimicrobials, Correct hypoglycemia and hypocalemia
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.

22. Fluid Refractory Shock
15min
Fluid Refractory Shock
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%
60 min
Catecholamine resistant shock

23. 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

24. 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
mcg/kg/min
Initially increases contractility/heart rate
High doses increase PVR
Noradrenaline
0.05 – 1 mcg/kg/min
Vasopressor
Increases PVR
Milrinone
mcg/kg/min
Phosphodiesterase inhibitor

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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.

32. Other treatment Maintain Glucose control Nutrition
Maintain Hb > 10g/dL
GI protection
Early CVVH

33. 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

34. 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

35. 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.