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. 

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Aim

This guideline aims to describe the key steps required to enable prompt recognition and rapid initial and ongoing management of paediatric sepsis and septic shock, for children presenting, or already admitted to, Perth Children’s Hospital. 

Risk

Sepsis is a major cause of morbidity and mortality in the paediatric population and can be very challenging to diagnose and manage.

For every hour a child remains in septic shock the mortality risk doubles.1

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.

Definitions 

Sepsis can be defined as a dysregulated host response to infection leading to life threatening end organ dysfunction.3

Septic shock is defined as sepsis with evidence of cardiovascular dysfunction.2-5 

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 2,12

1. Early recognition and initiation of treatment

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

  • Intravenous (IV) / intraosseous or,
  • Access central venous access device (CVAD) if present.

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

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

4. Rapid, judicious, fluid resuscitation of shocked patients: 10-20mL/kg sodium chloride 0.9% or balanced fluid boluses as a push aiming for shock reversal.

5. Early initiation of inotropes via peripheral access (if needed with early recourse to central venous access), for fluid refractory shock (≥40mL/kg fluid without shock reversal).

  • Followed by transfer to Paediatric Critical Care (PCC).

6. Source control (if possible).

Figure 1: Sepsis flowchart

Flowchart of sepsis recognition and management plan

Clinical recognition of sepsis

  • It is vital to maintain a high index of suspicion for sepsis as prompt recognition and treatment is crucial.
  • Sepsis can be particularly challenging to recognise in children. 
  • Children with early sepsis frequently present with non-specific symptoms and signs
  • There are a large number of sepsis mimics (e.g. viral illnesses) and infants and toddlers, in particular, can often appear very unwell, with significantly abnormal physiology, when febrile with such illnesses. 
  • Sepsis should be suspected on the basis of clinical features described below, leading to review by a senior clinician / Consultant. 
 

 Sepsis should be considered in a patient with suspected or proven infection AND/OR fever or hypothermia (temperature  ≥ 38°C or < 36°C) AND any of the following:

  • Altered mental status (e.g. reduced level of consciousness, lethargy, irritability, floppiness). 
  • Reduced peripheral perfusion, cool or mottled skin, prolonged central capillary refill time (CRT) ≥ 3 seconds and narrow pulse pressure (which can signify "cold shock").
  • Flushed skin with brisk CRT ( < 1 second), bounding pulses and wide pulse pressure (which can signify "warm shock"). 
  • Hypotension (if present is confirmatory of shock).
  • Tachycardia (persistent above limits for age) or bradycardia (particularly in neonates / infants).
  • Tachypnoea +/- hypoxia (not resulting from bronchiolitis, viral wheeze or asthma) or apnoeas in neonates / infants.
  • New onset / unexplained end-organ dysfunction.
  • Evolving petechial or purpuric rash.
  • Unexplained pain.
  • Increasing family, carer or clinician concern
  • Sepsis Recognition prompt triggered on the Observation and Response Chart.

 

A high level of family / carer or clinician concern including 'unwell' appearance should trigger review by a more senior clinician and escalation of care.

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 / incomplete immunisation status
  • Children with central venous access devices, indwelling medical devices
  • Recent surgery, burn or wound
  • Rural, remote or socioeconomic deprivation
  • Re-presentation to hospital

Management of Suspected Sepsis or Septic Shock

Initial Emergency Management: 

  • See flowchart above (Figure 1) for summary of initial management of sepsis or septic shock.  

In Emergency Department

  • Follow Paediatric Sepsis Recognition Escalation Pathway on the Observation and Response Chart (PARROT Chart) and escalate as appropriate for Sepsis Review
  • If a patient requires a Sepsis Review commence the PCH Sepsis Pathway and complete Screening section.
  • Manage all Emergency Department patients assessed as likely to have sepsis / septic shock in the resuscitation bay with senior support (Consultant or Advanced Trainee) and consideration of early PCC review.
  • Overnight the on-call Emergency Consultant must be called as soon as possible about all such patients.
  • The admitting Inpatient 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.

On the wards

  • Follow Paediatric Sepsis Recognition Escalation Pathway on the Observation and Response Chart (PARROT Chart) and escalate as appropriate for Sepsis Review
  • If a patient requires a Sepsis Review commence the PCH Sepsis Pathway and complete Screening section.
  • The responsible inpatient Consultant must be informed as soon as possible if, following medical review, the patient is felt 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.
  • 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 central vascular access devices (CVAD) should have these accessed.

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.
  •  The following tests would be appropriate in most instances: 
    • Venous blood gas (including lactate) 
    • Peripheral blood culture (even if antibiotics already given) 
    • Full blood count 
    • Blood glucose level 
    • Urea, electrolytes and creatinine
    • Liver function tests
    • Coagulation profile
    • C-Reactive Protein (CRP)
  • Normal blood test results (e.g. a normal CRP, white cell count or lactate) do not exclude sepsis.

Blood lactate

  • A normal lactate level does not exclude sepsis.
  • Observational studies have demonstrated an association between elevated blood lactate levels and adverse outcomes in paediatric septic shock.12
  • In a child with an elevated lactate (> 2mmol/L) and suspected infection, follow the appropriate “Sepsis recognition prompt” as per the Sepsis Recognition Escalation Pathway. 
  • A lactate > 4mmol/L in children with sepsis, has an association with increased mortality and adverse outcomes in some studies12. These patients require urgent senior medical or consultant review (within 5 minutes) and consideration of early PCC input.

Other investigations

  • In an unstable / shocked child, resuscitation and treatment should not be delayed by procedures such as urinalysis and lumbar puncture.
  • These procedures can be performed, as indicated, once the child has been stabilised and it is safe to do so.

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

  • Delayed antimicrobial therapy is an independent risk factor for mortality and prolonged organ dysfunction in paediatric sepsis.6
  • 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 
    • This must be undertaken within 60 minutes of sepsis recognition, ideally within 15 minutes2,7
    • Many antibiotics can be administered via the intramuscular route if necessary. 
  • For most patients, the following empiric options are suitable first-line antibiotic therapy. Allergies, local infection and resistance patterns should be considered. Cover may need to be broadened after initial resuscitation period.
  • Children who present with sepsis or septic shock should be discussed with the Infectious Diseases Consultant on call. 
  • For detailed up to date information on antibiotic choice refer to ChAMP Sepsis and Bacteraemia Guideline.

Empiric IV antibiotic choices

Community-acquired sepsis

Infant <4 weeks corrected gestational age (Meningitis NOT excluded):
Infant / child ≥ 4 weeks old:
  • Ceftriaxone (50 mg/kg/dose to a maximum of 2 grams) immediately then gentamicin (≥ 4 weeks to < 10 years: 7.5 mg/kg/dose (to a maximum dose of 320mg), ≥10 years - 18 years: 7 mg/kg/dose (to a maximum dose of 560mg))
  • Consider adding Vancomycin (15 mg/kg/dose  to a maximum initial dose of 750mg) IF:
    • Too unwell for lumbar puncture OR
    • Gram-positive cocci are seen on CSF Gram stain OR
    • Recent treatment with a penicillin, cephalosporin or carbapenem antibiotic.

Antibiotic Administration

  • Cefotaxime, ceftriaxone and gentamicin can be given as an IV push over 5 minutes
  • Ceftriaxone, cefotaxime and gentamicin can be given intramuscularly if intravenous or intraosseous access cannot be rapidly established (e.g. within 15 minutes)
  • Administration of these antibiotics should be prioritised over others (e.g. Vancomycin, which has a longer infusion time and cannot be given intramuscularly)
  • Vancomycin should be infused over 60 minutes OR at a rate of 10mg/minute whichever is longer
  • The recommendations above are for children at low risk for infection with a resistant organism
  • The following factors are associated with an increased risk of antibiotic resistance:
    • Recent infection / colonisation with a multi-resistant organisms including vancomycin-resistant Enterococci or carbapenem-resistant gram negative bacteria
    • Recent prolonged antimicrobial therapy
    • Overseas travel in the past 6 months
    • In the presence of the above risk factors, administer recommended empiric therapy and then contact the on-call Infectious Diseases consultant for further antimicrobial advice.

Healthcare-associated sepsis

Healthcare-associated sepsis includes suspected sepsis / septic shock in oncology or immunocompromised patients and suspected sepsis / septic shock in the presence of a central venous access device (CVAD).

Infant < 4 weeks old: contact Infectious Diseases
Infant / child ≥ 4 weeks old:
  • Cefepime IV 50 mg/kg/dose (to a maximum of 2 grams) followed by Vancomycin IV 15 mg/kg/dose (to a maximum initial dose of 750mg) 
  • +/- Gentamicin IV ≥ 4 weeks to < 10 years: 7.5 mg/kg/dose (to a maximum dose of 320mg), ≥ 10 years  18 years: 7 mg/kg/dose (to a maximum dose of 560mg).
    • Gentamicin should be considered in the patient who remains unstable despite initial antibiotic therapy and fluid resuscitation.
  • Cefepime and Gentamicin can be given intramuscularly if intravenous, CVAD or intraosseous access cannot be rapidly established (e.g. within 15 minutes). 
  • Discuss Oncology / Haematology patients early with the on-call Paediatric Oncology Fellow. Refer also to Fever in the Oncology Patient (or non-oncology neutropaenia) - ED guideline.

Fluid resuscitation

  • Fluid resuscitation should be titrated carefully. Both inadequate and excessive fluid resuscitation may be harmful. 2,8
  • Fluids should be considered in the same way as any other intravenously administered medication, with the potential benefits and harms for the individual patient considered prior to administration.  
  • Sodium chloride 0.9% should be used as the default initial resuscitation fluid.
  • Balanced fluids such as Plasma-Lyte 148 or Hartmann’s solution are are acceptable alternative choices for fluid resuscitation.12
  • Balanced fluids may be preferred in already acidotic or hyperchloraemic patients due to the potential for sodium chloride 0.9% to cause a hyperchloraemic acidosis.12
  • Administer 10-20mL/kg fluid boluses rapidly as a push or via pressure bag for patients with suspected septic shock.12
  • Target reversal of shock / normalised perfusion and restoration of heart rate to near normal values for age. 2
  • Repeated assessment of fluid status, perfusion, clinical condition and assessment for signs of fluid overload (new onset wheeze, worsening shortness of breath, hepatomegaly etc.) should be undertaken upon completion of each fluid bolus.2
  • Discussion with PCC is mandatory if needing ≥ 40 mL/kg fluid resuscitation.
  • Inotropes should be considered if shock persists after 40 mL/kg fluid.2
  • Fluid volumes of up to and over 60mL/kg may be needed in the first 60 minutes in some instances of septic shock. 2

Inotropes

  • The decision to commence inotropes / vasoactive agents should be made following discussion between the treating Emergency Consultant (if in ED) or Inpatient Consultant (if patient is on ward) and the Paediatric Critical Care Consultant / Registrar.
  • Can be given via peripheral IV or intraosseous access if central vascular access not available and whilst awaiting transfer to PCC.2, 9, 10 
  • Vigilant monitoring of peripheral IV site is essential for early detection and management of extravasation. 
  • Inotropes should be considered in patients with persistent shock / circulatory failure after 40mL/kg of fluid resuscitation.
  • Ensure the peripheral access is flushing well prior to commencement of inotropes. 
  • Take into account the 'dead-space' in lines and attached tubing when commencing infusions.

Adrenaline (epinephrine) infusion (via peripheral access)

  • Adrenaline is an appropriate first line option for most patients9,10  
  • A low strength standard concentration adrenaline infusion can be administered via peripheral intravenous catheter
  • Using adrenaline 1:1000 (1mg/mL) ampoules, add 6mg of adrenaline to a 1L bag of sodium chloride 0.9%
  • 1 mL/kg/hr of this infusion = 0.1 micrograms/kg/minute of adrenaline
  • Usually start at 0.1 micrograms/kg/minute i.e. 1mL/kg/hour
  • Titrate according to response, usually in the range from 0.05 – 0.3 micrograms/kg/minute
  • On occasion it may be appropriate to exceed 0.3 micrograms/kg/minute on the advice of the PCC Consultant
  • Refer to Emergency Department Infusion Calculator

Intubation

  • Intubation in sepsis / septic shock is a high risk procedure
  • May be required in the setting of:
    • Persistent shock or cardiovascular instability following fluid resuscitation or inotrope commencement.
    • Reduced level of consciousness e.g. Glasgow Coma Scale (GCS) < 9 or unresponsive. 
    • Imminent respiratory failure or airway compromise.
  • Key points for intubation of the septic child:
    • Ensure Emergency Consultant (if in ED), PCC and Anaesthetics have been called to attend.
    • Call a Code Blue if needing emergency assistance with airway control. 
    • Clearly assign roles and maximise resuscitation efforts prior to commencement of rapid sequence induction (RSI). 
    • Prepare for potential cardiorespiratory arrest with resuscitation doses of adrenaline (epinephrine) and fluid boluses drawn up and ready to administer.
    • If appropriate commence inotropes prior to RSI. 
    • All induction agents have the potential to worsen / precipitate shock in unstable septic patients.  
    • Choose medications with a relatively stable cardiovascular profile and avoid agents that are more likely to cause cardiovascular depression.(11) 
    • Reduced doses of induction agents may be sufficient in these patients.

Steroids

  • Children on long-term steroid therapy or with known adrenal insufficiency should receive stress dose steroids – refer to Adrenal insufficiency - ED guideline
  • Intravenous hydrocortisone therapy should also be considered for those with catecholamine resistant shock.2

References

  1. Han YY, Carcillo JA, Dragotta MA, et al. Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome. Pediatrics 2003; 112:793.
  2. Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock. Crit Care Med. 2017 Jun;45(6):1061-1093. doi: 10.1097/CCM.0000000000002425.
  3. Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287
  4. Goldstein B, Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6:2.
  5. Brierley J, Peters MJ. Distinct hemodynamic patterns of septic shock at presentation to pediatric intensive care. Pediatrics. 2008;122:752-759
  6. Weiss SL, Fitzgerald JC, Balamuth F, et al. Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. Crit Care Med 2014; 42:2409.
  7. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 4:580.
  8. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011; 364:2483.
  9. Ventura AM, Shieh HH, Bousso A, Góes PF, de Cássia F O Fernandes I, de Souza DC et al. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock. Crit Care Med. 2015 Nov;43(11):2292-302 2015 Nov;43(11):2292-302
  10. Ramaswamy KR, Singhi S, Jayashree M, et al. Double-Blind Randomized Clinical Trial Comparing Dopamine and Epinephrine in Pediatric Fluid-Refractory Hypotensive Septic Shock. Pediatr Crit Care Med 2016; 17:e502–e512
  11. BMJ Best Practice [Internet] Tong J. Sepsis in Children.  Last updated Nov 2017. Cited 2017 Dec 1. Available from: http://bestpractice.bmj.com/topics/en-gb/1201
  12. Weiss SL, Peters MJ, Alhazzani W, et al. Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Intensive Care Med 2020; 46:S10-S67.

Endorsed by:  Drugs and Therapeutics Committee  Date:  Nov 2022


 Review date:   Jun 2024


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