Paediatric Septic Shock Corrine Balit

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?

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 persitant 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 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

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 Peripheries Cool Warm Pulses Difficult to palpate Bounding Skin Mottled, pale Flushed Capillary refill Prolonged Blushing Mental state Altered Urine 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: FBC, 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 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

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.

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.

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

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

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.