Challenging Assumptions in Paediatric Sepsis Elliot Long No Disclosures 1

Challenging assumptions in paediatric sepsis Elliot Long No disclosures 1. What is paediatric sepsis?

• A clinical diagnosis What is paediatric sepsis?

• International consensus criteria: SIRS due to suspected infection 2 of:

• Fever (or hypothermia) • Tachycardia (or bradycardia) • Tachypnoea • Leukocytosis (or neutrophilia) How do international consensus criteria perform?

15% of ED presentations meet SIRS criteria for sepsis 90% of febrile ED presentations meet SIRS criteria for sepsis Of these, 80% are discharged home with no antibiotic therapy and no re-admission within 72 hours How do international consensus criteria perform?

1/3 of PICU admissions diagnosed with severe sepsis / septic shock by treating clinician did NOT meet consensus criteria, despite high associated mortality (17%) Are there alternatives? (sepsis-3 for kids)

• SIRS + organ dysfunction = higher risk of severe sepsis (?outcome) Are there alternatives? (sepsis-3 for kids)

• SIRS + organ dysfunction = higher risk of severe sepsis (?outcome) • Prognostic scores: • PIM-2 • PELOD-2 Are there alternatives? (sepsis-3 for kids)

• SIRS + organ dysfunction = higher risk of severe sepsis (?outcome) • Prognostic scores: • PIM-2 Both rely on physiological data not available early in resuscitation • PELOD-2 Are there alternatives? (sepsis-3 for kids)

• SIRS + organ dysfunction = higher risk of severe sepsis (?outcome) • Prognostic scores: • PIM-2 • PELOD-2 • Abridged scores (qSOFA for kids) • qSOFA • qPELOD

qSOFA = tachypnoea, altered mental status, hypotension mortality qSOFA = tachypnoea, altered mental status, hypotension

qSOFA ≧ 2 Sens 70%

Spec 48% mortality AUROC 0.60

Score range 0-3 qPELOD (SBP) > 2, mortality 19.8% qPELOD (MBP) > 2, mortality 15.9% AUROC (SBP or MBP) 0.82 Are there alternatives? (sepsis-3 for kids)

• SIRS + organ dysfunction = higher risk of severe sepsis (?outcome) • Prognostic scores: • PIM-2 • PELOD-2 • Abridged scores (qSOFA for kids) • qSOFA Not validated in ED setting • qPELOD Are there alternatives? (sepsis-3 for kids)

• SIRS + organ dysfunction = higher risk of severe sepsis (?outcome) • Prognostic scores: • PIM-2 • PELOD-2 • Abridged scores (qSOFA for kids) • qSOFA • qPELOD • Venous lactate

Lactate >36 mg/dL = >4 mmol/L Sens 0.20 Spec 0.92 OR 3.0 Lactate >36 mg/dL = >4 mmol/L Sens 0.20 Spec 0.92 OR 3.0

Useful for risk stratification? Are there alternatives? (sepsis-3 for kids)

• SIRS + organ dysfunction = higher risk of severe sepsis (?outcome) • Prognostic scores: • PIM-2 • PELOD-2 • Abridged scores (qSOFA for kids) • qSOFA • qPELOD • Venous lactate • Lactate >4mmol/L predictor of organ dysfunction (?outcome) Are there alternatives? (sepsis-3 for kids)

Are there alternatives? (sepsis-3 for kids)

• Variable prevalence and outcome data • ? Burden of disease • ? Hospitalisation costs • Difficult to monitor clinical care • Difficult to benchmark performance • Difficult to risk-stratify patients early • Difficult to design research projects 2. FBT increases CO 2. FBT increases CO

Why give fluid in the first place? 2. FBT increases CO

Why give fluid in the first place?

Assume impaired perfusion / inadequate oxygen delivery 2. FBT increases CO

Why give fluid in the first place?

Assume impaired perfusion / inadequate oxygen delivery

Fluid will increase CO and oxygen delivery

Oxygen delivery = CO x Hb x SpO2 For this to occur, FBT must a) Increase stressed venous volume (increase gradient for venous return) For this to occur, FBT must a) Increase stressed venous volume (increase gradient for venous return) b) Both ventricles must be operating on the ascending limb of the Frank-Starling curve

Normal cardiac function Cardiac output Cardiac

Right atrial pressure

Normal cardiac function Cardiac output Cardiac

Right atrial pressure Normal cardiac function

Cardiac output Cardiac Septic myocardial dysfunction

Right atrial pressure Only 50% of haemodynamically unstable patients are fluid responsive

Fluid responsiveness threshold

3. FBT increases MAP

MAP = CO x SVR Mean arterial blood pressure Time Systemic vascular resistance Time

4. Peripheral inotropes are dangerous 4. Peripheral inotropes are dangerous

Peripheral noradrenaline administered in 27 / 144 children for median 3h (IQR 2-4) No adverse events 102 patients with peripheral inotrope infusion (most commonly dopamine)

2/102 had extravasation, neither required intervention 55 patients, 3 complications, none requiring intervention (thrombophlebitis, local extravasation) Safety of peripheral intravenous administration of vasoactive medication. Cardenas-Garcia et al

734 patients, 19 (2%) extravasation, no tissue injury (treated with phentolamine / nitroglycerine paste) Summary

1. Sepsis is a clinical diagnosis

2. Fluid boluses result in a non-sustained increase in CO

3. Fluid boluses have limited ability to increase MAP

4. Peripheral inotrope infusions are safe, may more reliably result in sustained increase in CO