Paediatric Septic ShockCorrine Balit

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 look135am:You make your first assessment

HR 180Quiet, tired, opens eyesMod respiratory distress Cap refill 4 seconds

WHAT DO YOU DO?

Why are we worried about it?Still remains significant cause of morbidity and

mortality5-30% of paediatric patients with sepsis will

develop septic shock. Mortality rates in septic shock are 20-30% (up to

50% in some countries).

RecognitionMost people don’t recognise shockResuscitation must be done in a proactive time-

sensitive mannerEvery minute counts – “golden hour”Every hour without appropriate resuscitation and

restoration of blood pressure increases mortality risk by 40%

How do we define itSystemic Inflammatory Response SyndromeInfectionSepsisSevere SepsisSeptic Shock

Systemic Inflammatory Response Syndrome

Presence of 2 of the following criteria:Core Temp >38.5 or < 36 degreesMean HR > 2SD for age or persitant elevation over 0.5-4hrsIf < 1yr old: bradycardia HR < 10th centile for ageMean RR > 2 SD above normal for ageLeucocyte abnormality

SEPSISSIRS in presence of suspected or proven infection

Severe SepsisSepsis + one of the following

CV organ dysfunctionARDS2 or more organ dysfunction

Septic ShockSepsis + CV organ dysfunction

Cardiovascular dysfunctionDespite >40ml/kg Isotonic fluid bolus in 1 hour:

Decrease in BP <5th centile for ageNeed for vasoactive drug to maintain BP2 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 ageVery low birthweight infantsPrematurity Presence of underlying illness eg chronic lung,

cardiac conditions, malignancyCo-morbiditiesBoysGenetic factors

What makes you suspect shock?

Clinical ManifestationsFeverIncreased HRIncreased RRAltered mental stateSkin:

HypoperfusionDecreased capillary refillPetechiae, purpuraCool 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 ChildrenThis is main difference with adults. Blood pressure does not fall in septic shock until

very late. CO= HR x SVHR in children much higher therefore BP falling is

late.Pulse pressure is often useful

Normal: Diastolic BP > ½ systolic BP.

InvestigationsBasic bloods:

FBC, EUC, LFT, CMP, Coags, GlucoseInflammatory markers: PCT, CRPAcid- Base status

Venous or arterial blood gas:LactateBase deficit

InvestigationsSeptic Work up

Urine, blood, sputum culturesViral cultures: throat, NPA, faeces, Never do CSF in shocked patient

Imaging: CXR, CT, MRI, PET scan, ECHO,

Ultrasound

Management

General PrinciplesEarly RecognitionEarly and appropriate antimicrobialsEarly and aggressive therapy to restore balance

between oxygen delivery and demandEarly and goal directed therapy

What is Goal Directed Therapy?Based on studies in adults initiallyUse fluid resuscitation, vasoactive infusions,

oxygen to aim to restore balance between oxygen delivery and demand

Goals:Capillary refill < 2 secondsUrine ouptut > 1ml/kg/hrNormal pulses Improved mental stateDecreased lactate and base deficitsPerfusion 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 adrenalineEstablish 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 PressureCold ShockSVC < 70%

Low Blood PressureCold ShockSVC < 70%

Low Blood PressureWarm Shock

Add vasodilator or Type III PDE inhibitor

Titrate volume and adrenaline

Titrate volume & NoradrenalineConsider Vasopressin

ECMO

Drug Dose CommentsDopamine 2-20mcg/kg/min Historically 1st choice in kids

Alpha, beta and dopamine receptor activationCan be given peripherally

Dobutamine

5-10mcg/kg/min Chronotropic as well as inotropicAfterload reduction

Adrenaline 0.05- 1mcg/kg/min

Initially increases contractility/heart rateHigh doses increase PVR

Noradrenaline

0.05 – 1 mcg/kg/min

VasopressorIncreases PVR

Milrinone 0.25-0.75mcg/kg/min

Phosphodiesterase inhibitorAfterload reduction

Rivers et al, NEJM 2001Single Centre , RCT in Emergency DepartmentGoal directed vs standard care in septic adults in first 6

hours in EDGoal directed therapy consisted of

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

Showed significant decrease in mortalityCristisms: control group had higher mortality rate and

benefits may be because group was monitored more closely

Ceneviva et al, Pediatrics 1998Single centre, 50 childrenUsed goal directed therapy : CI 3.3-6Lmin/m2 in

children with fluid refractory shockMortality from sepsis decreased by 18% when

compared to 1985 study

De Oliveira ICM 2008RCT , single centreUse 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 2009Update of 2002 guidelines for goal directed

therapyLook 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 accessFluid removal considered early

What about Hydrocortisone?ControversialRational 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 hydrocortisoneAt 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 2008Mutlicentre, RCTHydrocortisone vs placebo in septic shockNo significant difference in mortality Many criticisms

Inadequate power Selection bias

Evidence- paediatricsNo RCT in paediatric patients with sepsis Markovitz : PCCM 2005

Retrospective cohort study , 6000 paediatric patientsSystemic steriods associated with increased

mortalityBut no control in place for severity of illness or for

dose.

Other treatmentMaintain Glucose controlNutritionMaintain Hb > 10g/dLGI protectionEarly CVVH

Activated Protein CInhibits factors Va and VIIIa – prevent generation

of thrombinDecreased inflammation through inhibition of

platelet activation, neutrophil recruitmentInitially had popularity as possible treatment

option in septic shockConcern with it is risk of serious haemorrhage

RESOLVE Study, Lancet 2007RCT, multicentre, international study in 477

children with severe sepsis. Compared APC to placebo for 96 hrsPrimary end point: time to complete organ failure

resolutionStudy stopped early as interim analysis showed no

benefit More bleeding in APC group but not significantly

different

ECMOStudy published this month from RCH MelbourneLooked at ECMO use in paediatric septic shock96% had at least 3 organ failure and 35% had a

cardiac arrest prior to ECMO23 patients with refractory septic shock received

central ECMO17 (74%) patients survived to be discharged from

hospital.