Sepsis, septic shock and MODS

Definition and Overview

Sepsis in children is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a subset of sepsis with cardiovascular dysfunction persisting despite adequate fluid resuscitation, characterised by the need for vasoactive support and/or evidence of tissue hypoperfusion (elevated lactate, altered mental state, prolonged capillary refill).

Paediatric sepsis is distinct from adult sepsis in several respects:

• Children mount a more vigorous inflammatory response and may compensate haemodynamically until late decompensation
• Hypotension is a late and pre-terminal sign in children; the absence of hypotension does not exclude shock
• Age-specific vital sign thresholds must be used (see table below)
• The commonest phenotype of paediatric septic shock is cold shock (high SVR, low CO), in contrast to adults who more commonly present with warm vasodilatory shock

Epidemiology:

• Incidence approximately 2-4% of PICU admissions in Australia and New Zealand; mortality 4-10% in high-income settings, higher in resource-limited environments
• Leading organisms vary by age: Group B Streptococcus and gram-negatives in neonates; Streptococcus pneumoniae, Neisseria meningitidis in infants and toddlers; Staphylococcal and gram-negative enteric pathogens across all ages

Age-Specific Physiological Thresholds

A practical bedside approximation for the lower limit of normal systolic BP in children aged 1-10 years: $\text{SBP}_{\min} = 70 + (2 \times \text{age in years})\,\text{mmHg}$.

Pathophysiology

Initial Inflammatory Cascade

Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) activate pattern recognition receptors (toll-like receptors), triggering release of pro-inflammatory cytokines (TNF-$\alpha$, IL-1, IL-6). This drives:

• Endothelial activation, increased vascular permeability, and third-space fluid shifts
• Coagulopathy (consumptive coagulopathy, DIC)
• Mitochondrial dysfunction and impaired oxygen utilisation

Haemodynamic Phenotypes in Children

$$\text{DO}_2 = \text{CO} \times \text{CaO}_2 = (\text{HR} \times \text{SV}) \times (1.34 \times \text{Hb} \times \text{SpO}_2 + 0.003 \times \text{PaO}_2)$$

• Cold shock (most common in children): elevated SVR, reduced cardiac output, poor peripheral perfusion, mottled cool extremities, prolonged CRT $>2$ seconds. Adrenaline-responsive.
• Warm shock: reduced SVR, bounding pulses, flash CRT; more common in older children and adolescents, and in gram-negative/endotoxin-mediated sepsis. Noradrenaline-responsive.
• Progression to refractory shock involves absolute adrenal insufficiency, myocardial dysfunction, and multi-organ failure

Clinical Recognition

Red Flag Features

• Altered mental state, inconsolable irritability, or decreased responsiveness
• Prolonged capillary refill time $>2$ seconds or flash CRT $<1$ second
• Mottled skin, pallor, or peripheral cyanosis
• Tachycardia out of proportion to fever
• Oliguria (urine output $<1\,\text{mL/kg/hr}$ in children, $<0.5\,\text{mL/kg/hr}$ in adolescents)
• Non-blanching petechial or purpuric rash (meningococcaemia until proven otherwise)
• New hepatomegaly (indicator of venous congestion and right heart dysfunction)

PICU Triage: Recognising Fluid-Refractory Shock

Fluid-refractory septic shock is defined as persistent signs of shock after $\geq 40\,\text{mL/kg}$ of isotonic crystalloid within the first hour. These children require urgent vasoactive support, ICU admission, and reassessment of diagnosis.

Investigations

Lactate is a key marker: elevated lactate in the setting of shock mandates early aggressive resuscitation even if BP is maintained. Serial lactate guides response to therapy.

Management

Step 1: Simultaneous Resuscitation and Recognition (0-15 minutes)

1. High-flow oxygen via non-rebreather mask; prepare for early intubation if work of breathing is high or GCS declining
2. Establish two large-bore IV cannulae or intraosseous (IO) access; IO is first-line if IV access fails after 90 seconds
3. Blood cultures (do not delay antibiotics $>1$ hour)
4. Point-of-care glucose, lactate, gas
5. Activate sepsis pathway and notify PICU/retrieval team early

Step 2: Fluid Resuscitation (First Hour)

• Initial bolus: $10\,\text{mL/kg}$ isotonic crystalloid (0.9% NaCl or Hartmann's/PlasmaLyte) over 5-10 minutes, with reassessment after each bolus
• Repeat boluses of $10\,\text{mL/kg}$ to a maximum of $40\,\text{mL/kg}$ in the first hour, titrating to clinical response (CRT, HR, mental state, urine output)
• After $20\,\text{mL/kg}$: reassess for signs of fluid overload (new hepatomegaly, increased work of breathing, worsening oxygenation); if present, transition earlier to vasoactive support
• Neonates and children with known or suspected cardiac disease: use $5\,\text{mL/kg}$ boluses with very careful reassessment; avoid large volume resuscitation without senior review

Key divergence from adult practice: The FEAST trial demonstrated harm from liberal bolus therapy in resource-limited settings without ICU backup. In Australian and New Zealand PICUs, bolus resuscitation with close monitoring and early escalation to vasoactives remains standard; routine restriction of all fluid boluses is not supported in the well-resourced PICU environment, but avoidance of fluid overload $>10$% body weight is a clear goal.

Step 3: Antimicrobials (within 1 hour of recognition, ideally $<$30 min for shock)

• Empiric broad-spectrum antibiotics should be given within 60 minutes of recognition (within 30 minutes for septic shock)
• Default regimen in most Australian and New Zealand PICUs: Piperacillin-tazobactam $100\,\text{mg/kg}$ (piperacillin component) IV 6-hourly (max $4\,\text{g}$ per dose) plus Gentamicin $7\,\text{mg/kg}$ IV daily (neonates: age-adjusted dosing, consult pharmacy)
• Add Vancomycin $15\,\text{mg/kg}$ IV 6-hourly (max $750\,\text{mg}$ per dose) if: central line in situ, gram-positive source suspected, MRSA risk, or neutropenic patient
• Add Aciclovir $10-15\,\text{mg/kg}$ IV 8-hourly if HSV encephalitis or neonatal HSV is possible
• Antifungal (Caspofungin $70\,\text{mg/m}^2$ loading, then $50\,\text{mg/m}^2$ daily) in immunocompromised or prolonged broad-spectrum antibiotic exposure
• De-escalate at 48-72 hours when cultures and sensitivities are available

Step 4: Vasoactive Support (Fluid-Refractory Shock)

Initiate vasoactives if shock persists after $\geq 20\,\text{mL/kg}$ OR signs of fluid overload appear. Do not wait for $40\,\text{mL/kg}$ if clinical deterioration is evident.

• Peripheral vasoactives are acceptable for short-term stabilisation (30-60 min) while central access is established
• Central venous access should be obtained early for reliable drug delivery and CVP/ScvO$_2$ monitoring
• ScvO$_2$ target $\geq 70$%: if $<70$%$ despite fluid and vasopressor optimisation, consider transfusion to Hb $\geq 80\,\text{g/L}$ or addition of inotrope

Step 5: Source Control

• Drain any accessible collection (abscess, empyema, infected effusion) within 6-12 hours of identification
• Remove infected intravascular devices (central lines, PICC lines) where source of bacteraemia; balance against need for access
• Surgical consultation early for necrotising fasciitis, intestinal perforation, or undrained pus

Step 6: Corticosteroids (Catecholamine-Resistant Shock)

• Indicated in catecholamine-resistant septic shock and when adrenal insufficiency is suspected (prolonged steroid use, adrenal haemorrhage, purpuric rash of meningococcaemia)
• Hydrocortisone $1-2\,\text{mg/kg/dose}$ IV 6-hourly (max $50\,\text{mg}$ per dose); some units use a continuous infusion
• Cosyntropin stimulation testing is not required before commencing in the acute setting

Monitoring Targets During Resuscitation

Special Considerations

Neonatal Sepsis at the PICU Interface

• Group B Streptococcus, Listeria, and gram-negative enteric organisms dominate early-onset; coagulase-negative staphylococci and Candida in late-onset NICU sepsis
• Empiric regimen: Benzylpenicillin $60\,\text{mg/kg}$ IV 12-hourly (term) plus Gentamicin $5\,\text{mg/kg}$ IV 36-hourly (term neonate); adjust for gestation and age
• Neonates may present with temperature instability, poor feeding, apnoea, or metabolic acidosis rather than classic sepsis signs
• Avoid prolonged fasting; early dextrose-containing fluids to prevent hypoglycaemia

Meningococcaemia

• Ceftriaxone $100\,\text{mg/kg}$ IV (max $4\,\text{g}$) stat as soon as blood cultures drawn; do not delay for LP
• Anticipate DIC, adrenal haemorrhage (Waterhouse-Friderichsen), and rapid progression to refractory shock
• Prophylaxis for close contacts: notify public health; ciprofloxacin or rifampicin per weight-based dosing

Immunocompromised Host

• Fever in a neutropenic child (ANC $<0.5 \times 10^9/\text{L}$) is a medical emergency
• Empiric coverage must include gram-negative cover including Pseudomonas: Piperacillin-tazobactam or Meropenem $20\,\text{mg/kg}$ IV 8-hourly
• Lower threshold for antifungals, antivirals; consult haematology/oncology early

Retrieval and Transport

• Stabilise before transfer: establish airway if required, secure vascular access, commence vasoactives via peripheral line if needed
• Communicate ISBAR-structured handover; document resuscitation volumes, antibiotics given with times and doses
• Anticipate deterioration in transport: ensure vasoactive infusions are reliable, have adrenaline drawn up for arrest ($10\,\mu\text{g/kg}$ IV/IO)

Complications

• Fluid overload: cumulative fluid balance $>10$% body weight is independently associated with worse outcomes; use diuretics or early CRRT if oliguric and fluid-overloaded once haemodynamically stable
• PARDS: lung-protective ventilation if intubated ($V_T$ $5-7\,\text{mL/kg}$ IBW, PEEP titration, $\text{FiO}_2$ minimised)
• AKI: monitor creatinine, urine output, electrolytes; avoid nephrotoxic drug accumulation (aminoglycosides: single daily dosing, levels)
• DIC: FFP $10\,\text{mL/kg}$ IV, cryoprecipitate $5\,\text{mL/kg}$ IV, platelets $10\,\text{mL/kg}$ IV as guided by coagulation and bleeding
• Hypoglycaemia: common in infants; check glucose every 1-2 hours during acute resuscitation; treat with $2\,\text{mL/kg}$ of 10% dextrose IV
• Hypocalcaemia: ionised calcium $<1.1\,\text{mmol/L}$ impairs cardiac contractility; replace with Calcium gluconate $0.1\,\text{mmol/kg}$ IV slowly

PICU Exam Framing: Viva Anchors

• Always state age-specific thresholds when asked to recognise shock; hypotension is a late sign in children
• Fluid bolus 10 mL/kg with reassessment is the paediatric standard; not 30 mL/kg as in adult Surviving Sepsis; distinguish your practice
• Cold shock = adrenaline first; warm shock = noradrenaline first; this is a high-yield differentiator
• When asked about corticosteroids: reserve for catecholamine-resistant shock; hydrocortisone at stress dosing
• Antibiotics within 60 minutes, ideally within 30 minutes for established shock: state the time target explicitly in viva
• Document and communicate: fluids given, antibiotics with times, vasoactive doses, and response are all essential for safe retrieval handover and PICU admission