Sepsis recognition and management

Disclaimer These guidelines have been produced to guide clinical decision making for the medical, nursing and allied health staff of Perth Children’s Hospital. They are not strict protocols, and they do not replace the judgement of a senior clinician. Clinical common-sense should be applied at all times. These clinical guidelines should never be relied on as a substitute for proper assessment with respect to the particular circumstances of each case and the needs of each patient. Clinicians should also consider the local skill level available and their local area policies before following any guideline.  Read the full CAHS clinical disclaimer

Aim

To enable prompt recognition of sepsis and septic shock and guide the initial and ongoing management of sepsis and septic shock, for children presenting, or already admitted, to Perth Children’s Hospital (PCH). 

Risk

• Sepsis is a major cause of morbidity and mortality in the paediatric population and can be very challenging to diagnose and manage.¹
• For every hour a child remains in septic shock the mortality risk doubles.²
• Care delivered in the first hour after sepsis identification is crucial in ensuring the optimum outcome for the patient.²
• Oncology patients with suspected sepsis or septic shock are to be managed according to this guideline with early input from the Oncology Fellow
  • Refer to the Fever in the Oncology Patient - Emergency Department Guideline for key additional information, including a pathway for the initial management of Fever in the Oncology Patient.
• Neonates with suspected sepsis or septic shock presenting to the Emergency Department or being managed at PCH outside of the Neonatal Intensive Care Unit (NICU), are managed according to this guideline.
  • Neonates cared for in NICU Ward 3B at PCH or at King Edward Memorial Hospital (KEMH) should be managed in accordance with the KEMH Neonatal Sepsis guidelines Sepsis: Neonatal Guideline or Sepsis Calculator – Assessment of Early-Onset Sepsis in Infants > 35 weeks.
  • Refer to Neonatology Admission to NICU KEMH and PCH Guideline for NICU 3B admission criteria.

Definitions 

Sepsis is a dysregulated host response to infection leading to life threatening end organ dysfunction.^4-6

Septic shock is defined as sepsis with evidence of cardiovascular dysfunction.^3-8 

Hypotension is generally a late sign and is not required to diagnose septic shock in children. However, the presence of hypotension is confirmatory of shock.

Key Points for Managing Sepsis and Septic Shock ^3,9

1. Early recognition and initiation of treatment. 

2. Rapid vascular access, within 5 minutes of recognition of septic shock.  

3. Empiric antibiotic therapy as soon as possible and within 60 minutes of septic shock recognition:

• Administer as soon as possible after vascular access obtained.
• If unable to gain vascular access rapidly (e.g. within 15 minutes), give initial dose of antibiotics intramuscularly (IM).
• Blood sampling should be attempted at time of vascular access but must not delay treatment.

4. Rapid, judicious, fluid resuscitation of shocked patients:

• 10-20 mL/kg sodium chloride 0.9% or balanced fluid boluses as a push aiming for shock reversal (10 mL/kg boluses for neonates).

5. Early initiation of inotropes / vasoactive support via peripheral access for fluid refractory shock (≥40 mL/kg fluid without shock reversal).

• Followed by transfer to Paediatric Critical Care (PCC) or NICU 3B.

6. Source control (if possible).

Figure 1: Sepsis Recognition and Management Flowchart

Sepsis Recognition Sepsis should be considered in a patient with suspected or proven infection AND/OR fever / hypothermia (temperature ≥ 38 ºC or < 36 ºC) AND one or more signs of impaired tissue perfusion below: Tachycardia disproportionate to fever, anxiety, medications Bradycardia Cold shock: capillary refill time (CRT) ≥ 3 seconds, cool peripheries, cool or mottled skin, reduced peripheral pulses, narrow pulse pressure Warm shock: CRT < 1 second, bounding pulses, wide pulse pressure Altered level of consciousness (LOC) / drowsiness / irritability Hypotension (a late sign of septic shock in children) New onset end organ dysfunction Evolving petechial or purpuric rash Unexplained pain OR Sepsis / Septic shock suspected following medical review triggered by Sepsis Pathway

Resuscitation/Initial Management - Follow Sepsis Pathway Time target: 0-15 minutes Call for help Support airway, apply oxygen Establish vascular access Aim for vascular access within 5 min in septic shock Take bloods: Glucose, venous blood gas (including lactate), blood cultures, full blood count, urea, electrolytes and creatinine, liver function tests, coagulation profile and C-reactive protein, extra ETDA blood tube (for PCR) Do not allow blood collection to delay antibiotics / fluid more than a few minutes. Commence antibiotics (IM antibiotics if vascular access not rapidly established i.e., < 15 mins in septic shock) Commence fluid resuscitation with 10-20 mL/kg of sodium chloride 0.9% (as a push not via infusion pump) for patients with suspected shock (10 mL/kg boluses for neonates) Correct hypoglycaemia (if present) with 2 mL/kg glucose 10%. Then confirm correction.

Ongoing Resuscitation - Follow Sepsis Pathway Time target: 15-60 minutes Continue fluid resuscitation with repeat boluses of 10-20 mL/kg of sodium chloride 0.9% as needed (10 mL/kg boluses for neonates) Target reversal of shock, improved perfusion / CRT, heart rate, clinical condition. Monitor closely for signs of fluid overload (e.g. new onset wheeze, worsening shortness of breath, hepatomegaly). Consider balanced fluids (Plasma-Lyte 148 or Hartmann’s solution) if patient is acidotic or hyperchloraemic. If circulatory failure persists after 40 mL/kg fluid bolus: Obtain additional vascular access. Mandatory PCC/NICU 3B review if not already present. Consider peripheral inotropes - discuss with the PCC/NICU 3B Consultant and the Emergency Department (ED) Consultant (if in ED) or Inpatient Consultant (if on ward). Consider further fluid bolus (must be discussed with Consultant first). Prepare for intubation (particularly if altered LOC). Arrange transfer to PCC/NICU 3B.

 

Clinical recognition of sepsis

• Sepsis can be challenging to recognise.
• Children with early sepsis often present with non-specific symptoms and signs.
• It is vital to maintain a high index of suspicion for sepsis as prompt recognition and treatment is crucial.
• Utilise the Sepsis Pathway to aid in sepsis recognition and escalation of suspected sepsis.
• Consider sepsis in patients with features described on the Figure 1: Sepsis Recognition and Management Flowchart.

Sepsis mimics and differential diagnoses:

• Many conditions can mimic sepsis.
• Children presenting with a fever may appear unwell with abnormal vital signs, however most children with a fever do not have sepsis.
• A period of observation may help differentiate children with fever due to self-limited viral infection (abnormal vital signs that normalise over time) and those that require further work-up and management for potential early sepsis (abnormal vital signs that persist or worsen over time, clinical deterioration or persistently unwell appearance).
• Several serious neonatal conditions can mimic sepsis, including but not limited to congenital cardiac lesions, bowel obstruction and other abdominal emergencies, metabolic disorders, seizures, and non-accidental injury.
  • These conditions should be considered in the differential diagnosis for neonates presenting with potential sepsis.
  • Always remember to check femoral pulses are palpable in an unwell neonate.

High risk groups

The following children have a higher risk of sepsis and the threshold for investigation / management of sepsis should be lower:

• Infants less than 3 months of age
• Immunosuppression due to chemotherapy, long-term steroids, other immunosuppressants, asplenia and other chronic medical conditions
• Unimmunised / incompletely immunised children
• Children with central venous access devices (CVAD), indwelling medical devices
• Complex / chronic medical conditions
• Recent surgery, burn or wound
• Children living in rural and / or remote locations or living in socioeconomically deprived settings or with delayed access to healthcare
• Culturally and linguistically diverse children
• Children with multiple presentations to healthcare providers (including GP) with the same infective illness
• Family and/or clinician concern

Management of Suspected Sepsis or Septic Shock

Initial Emergency Management: 

• See Figure 1: Sepsis Recognition and Management Flowchart (above) for summary of initial management of sepsis / septic shock.  

In Emergency Department

• Follow Sepsis Pathway to aid sepsis recognition and guide appropriate escalation of care and clinical response.
• Manage all Emergency Department patients with suspected septic shock in the resuscitation bay with senior support (Consultant or Fellow) and consideration of early PCC or NICU 3B review. Have a low threshold to move patients with suspected sepsis without shock to the resuscitation bay.
• Overnight, the on-call Emergency Consultant / Fellow must be called, as soon as possible, about all patients with suspected septic shock.
• The admitting in-patient Consultant must be advised of all patients with suspected sepsis or septic shock to be admitted under their care, prior to transfer to the ward. This would normally be done by the Admitting Registrar.

On the wards

• Follow the Sepsis Pathway to aid sepsis recognition and guide appropriate escalation of care and clinical response.
• The responsible in-patient Consultant must be informed as soon as possible if, following medical review, the patient is likely to be septic or have septic shock.

Vascular Access

• This is a priority and should be tasked to an experienced clinician.
• For patients with septic shock, if unable to gain intravenous access within 5 minutes or after two attempts, insert intraosseous access (refer to the PCH Intraosseous Access Guideline). It may be appropriate to opt for intraosseous access initially in critically unwell patients or those in whom access is clearly going to be difficult.
• Patients with CVAD in-situ should have these accessed.
• Consider use of an umbilical venous catheter (UVC) in neonates < 7 days of age.

Blood tests

• If possible, blood tests should be taken at the time vascular access is obtained, with priority given to venous blood gas and blood culture collection. 
• Antibiotic administration and fluid resuscitation must not be delayed by repeated attempts to collect blood samples.
• Normal blood test results (e.g. a normal C-Reactive Protein (CRP), white cell count or lactate) do not exclude sepsis.
• The following tests would be appropriate in most instances:
  • Blood glucose
  • Venous blood gas (including lactate)
  • Peripheral blood cultures (even if antibiotics already given - preferably two BACTEC Peds Plus/F bottles from two different sites)
  • Full blood count (FBC)
  • Urea, electrolytes and creatinine
  • Liver function tests (LFTs)
  • Coagulation profile
  • CRP
  • Additional EDTA tube (if possible) for PCR testing e.g., Meningococcal, Pneumococcal, Group A Streptococcal PCR

Hypoglycaemia

• All children should have a blood glucose level checked.
• Correct hypoglycaemia (blood glucose level < 3 mmol/L) with 2 mL/kg of glucose 10%. Repeat blood glucose level after treatment and give further treatment as indicated by repeated measurements.

Blood lactate

• A normal lactate level does not exclude sepsis.^10,11
• Observational studies have demonstrated an association between elevated blood lactate levels and adverse outcomes in paediatric septic shock.⁹
• An elevated lactate (> 2mmol/L) and suspected infection, follow the appropriate prompt as per the Sepsis Pathway. 
• A lactate > 4 mmol/L in children with sepsis, has an association with increased mortality and adverse outcomes in some studies.⁹ These patients require urgent (within 5 minutes) senior clinician review as per the Sepsis pathway. Early critical care input should be considered.

Other investigations

• A urine sample is recommended in all children with sepsis / suspected sepsis.
• A cerebrospinal fluid sample is recommended for all children with suspected meningitis including all neonates (< 4 weeks postnatal age) with sepsis / suspected sepsis. Lumbar puncture should not performed on an unstable, shocked or coagulopathic child or if there is evidence of raised intracranial pressure or any other contraindication (refer to the PCH Lumbar Puncture Guideline).
• Diagnostic imaging as appropriate based on suspected source / differential diagnosis
• Consider ammonia and urine metabolic screen and other investigations as necessary to investigate differential diagnoses for sepsis in neonates.

Hypoglycaemia

• All children should have a blood glucose level checked.
• Correct hypoglycaemia (blood glucose level < 3mmol/L) with 2mL/kg of glucose 10%. Repeat blood glucose level after treatment and give further treatment as indicated by repeated measurements.

Antibiotics

• For detailed up to date information on antibiotic choice refer to PCH ChAMP Sepsis and Bacteraemia Guideline.
• Delayed antimicrobial therapy is an independent risk factor for mortality and prolonged organ dysfunction in sepsis.^{9, 11}
• Initial empiric intravenous antibiotic therapy must be administered as soon as possible after vascular access is obtained, prior to or concurrently with the first fluid bolus.
  • Within 60 minutes of recognition of septic shock, ideally within 15 minutes.⁹ All IV antimicrobials in the ChAMP Sepsis and Bacteraemia Guideline are suitable for IM administration except for vancomycin and aciclovir.
• For most patients, the following empiric options are suitable first-line antibiotic therapy. Allergies, local infection and resistance patterns should be considered.
• In children with progressive sepsis or severely unwell with sepsis or meningitis despite appropriate initial empiric antibiotic therapy, reassess and reconsider source of infection, differential diagnoses and discuss broadening antimicrobial therapy with the on-call Infectious Diseases physician.
• If a child has any factors associated with an increased risk of antibiotic resistance recent including infection/colonisation of a multi-resistant organism e.g., vancomycin-resistant Enterococci or carbapenem-resistant gram-negative bacteria; recent prolonged antimicrobial therapy; overseas travel in the past 6 months administer recommended empiric therapy and contact the on-call Infectious Diseases physician for further antimicrobial advice.

Antibiotic Administration

Cefepime, cefotaxime, ceftriaxone and gentamicin can be given as an IV push over 5 minutes or be given intramuscularly and administration of these antibiotics should be prioritised over others which have a longer infusion time and cannot be given intramuscularly. Vancomycin should be infused over 60 minutes OR at a rate of 10 mg/minute whichever is longer.

* Severely unwell with sepsis can be defined as any of the following:

• evidence of end-organ dysfunction.
• apnoeas or airway compromise requiring advanced airway management.
• respiratory failure or need for invasive or non-invasive respiratory support.
• shock or need for circulatory support fluid bolus/inotropes.
• reduced conscious state.
• coagulopathy.
• need for intensive care input or admission; or
• senior clinician concern that the child is “severely unwell”.

Empiric IV Antibiotic Choices – Healthcare Acquired Sepsis

Healthcare-Associated Neonatal Sepsis i.e., presumed serious bacterial infection with no known source (< 4 weeks postnatal age)	IV gentamicin (doses as per neonatal guidelines) AND IV vancomycin (doses as per neonatal guidelines)
Healthcare-Associated Sepsis i.e., presumed serious bacterial infection with unknown source (≥ 4 weeks postnatal age) Includes community acquired sepsis with a central venous access device (CVAD) in place	IV cefepime 50 mg/kg/dose (max of 2 grams) 8 hourly AND IV vancomycine 15 mg/kg/dose (max initial dose of 750 mg)  6 hourly IF SHOCKED, ADD IV gentamicind (refer to monograph for dose)

Fluid resuscitation

Endorsed by:	Drugs and Therapeutics Committee	Date:	Mar 2024
		Review date:	Feb 2027

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