sepsis / septicaemia

see also:

• meningococcal septicaemia
• infectious diseases
• the febrile child
• the febrile adult
• febrile neutropenia
• NSW CEC Sepsis Kills program
• NEJM 2014: ProCESS Trial
  • as long as early recognition and commencement of ED care, there was no significant advantage, with respect to mortality or morbidity, of protocol-based resuscitation over bedside care that was provided according to the treating physician’s judgment.
  • no significant benefit of the mandated use of central venous catheterization and central hemodynamic monitoring in all patients
• NSW CEC adult sepsis pathway chart (pdf)
• JAMA 2016: The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)
• JAMA Dec 2018 - corticosteroids appear to improve outcomes in sepsis
• Western health adult sepsis pathways (intranet only):
  • sepsis flowchart 2019 for ED

• sepsis now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection
• organ dysfunction can be determined by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more which reflects an overall mortality risk of approximately 10% in a general hospital population with suspected infection
• the SIRS concept has been removed as it performed poorly
• septic shock can be identified with a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum serum lactate and lactic acidosis level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation. With these criteria, hospital mortality is in excess of 40%.

• positive if:
  • RR > 22/min
  • altered mentation, and,
  • systolic BP < = 100mmHg
• can quickly identify patients with infection who are likely to have a prolonged ICU stay or to die in the hospital

• purpuric rash consistent with meningococcal septicaemia
• immunocompromised with either fever, hypothermia or history of chills (these patients need iv antibiotics within 30 minutes)
• adult patients with two or more of the following are also at risk of rapid deterioration and should be considered for immediate activation of resuscitation as per sepsis pathway:
  • systolic BP < 100mmHg
  • recent change in mental status
  • lactate > 2 mmol/L

• these conditions may cause a SIRS-like state and the patient may not be septic nor have SIRS despite fevers:
  • drug overdose
  • status asthmaticus
  • status epilepticus
  • active GI bleeding
  • burns
  • major trauma
  • heat illness and heat stroke
  • thyroid storm
• NFR status

• immunocompromised
• indwelling medical devices
• recent surgery or invasive procedure
• history of fever, muscle pains, or rigors
• bone or joint pain or swelling
• skin - cellulitis or wound discharge
• possible UTI - dysuria, frequency, odour
• abdominal pain or peritonism
• chest infection - cough, SOB
• neuro: decreased mental state, delirium, neck stiffness, headache

• in adults, at least two of:
  • temp > 38.3deg. C
  • temp < 36deg. C
  • heart rate > 90/min
  • respiratory rate > 20/min
  • WCC > 12
  • WCC < 4
  • acutely altered mental state
  • blood glucose > 6.6 in the absence of known diabetes

• if petechial rash or purpura, Mx as for meningococcal septicaemia
• pneumonia
• urinary tract infections (UTIs) / cystitis
• intraperitoneal infection - peritonitis, appendicitis, diverticulitis, perforated peptic ulcer
• biliary tract infection - cholecystitis, ascending cholangitis - see also RUQ pain
• bloodstream catheter infection
• bone or joint infection
• CNS infection - meningitis
• spinal infection (especially if IVDU) - epidural abscess - consider emergent MRI
• infective endocarditis (including SBE)
• ENT infection
• gynae. infection - endometritis, pelvic inflammatory disease (PID), retained tampon - toxic shock syndrome
• implantable device infection
• foreign body infection
• skin/soft tissue infection
• wound infection
• the febrile returned traveller
• rarely, iatrogenic via contaminated saline used for IV or wound irrigation may cause deaths:
  • Ralstonia picketti has caused outbreaks in Australian hospitals in 1990 (6 died) and in 2023 (Qld and NSW private hospitals with the Interpharma saline sourced from India and Greece causing over 43 cases)
• other - consider fungal infections

• acute blood / fluid loss
• pancreatitis
• pulmonary embolism
• myocardial infarction
• mesenteric ischaemia - does the patient have AF?
• anaphylaxis
• transfusion reaction
• autoimmune disorder
• burns/other trauma
• heat illness and heat stroke
• thyroid storm

• SIRS plus:
  • infection suspected, plus either:
  • systolic BP < 90, MAP < 65, lactate > 2 or other evidence of new organ dysfunction suggested by either:
    • creatinine > 177
    • bilirubin > 34
    • platelets < 100
    • INR > 1.5
    • APTT > 60sec
    • new or increased oxygen needs to keep SaO₂ > 90%
    • urine output < 0.5ml/kg/hr for 2hours

• if petechial rash or purpura, Mx as for meningococcal septicaemia
• if meningism, Mx as for meningitis
• otherwise:
  • iv access - at least 18G
  • oxygen to maintain sats > 95% (or to 88-92% if COPD or chronic type II resp. failure)
  • FBE, U&E, CRP, LFT, amylase, lipase, glucose, lactate and clotting + Xmatch
  • blood cultures x 2 sets from separate sites (or 1 set from each lumen of a intravascular device or port plus 1 peripheral set)
  • search for infective causes
    • CXR, urine culture, wound culture
    • consider CT chest/abdo/pelvis where indicated
  • iv antibiotics preferably within 1hr (30 minutes if immunocompromised) (see below under severe sepsis for antibiotic choice)
  • 500mL normal saline or Hartmanns bolus stat if BP < 100mmHg or if lactate > 2 mmol/L
    • if no response, repeat once
    • look for signs of fluid overload / pulm. oedema especially if known cardiac failure or elderly
    • if still hypotensive may need early inotropes
  • hourly obs
  • control source of infection where possible:
    • eg. drainage of abscess, surgery where indicated

• iv access
• FBE, U&E, LFT, amylase, lipase, glucose, lactate and clotting + Xmatch
• 30 minutely obs
• monitor fluid balance
• iv NSaline (aiming for a CVP of 8-12mmHg, MAP >= 65mmHg):
  • if systolic BP < 90 or lactate > 4 then
    • give 20ml/kg stat then boluses of 200-500ml NSaline if systolic BP falls below 90 again.
  • otherwise, give 500-1000ml NSaline over 30-60min
• urgent senior medical consultation
• blood cultures
  • take 2 sets but do not delay administration of antibiotics
• iv antibiotics within 60 minutes according to most likely aetiology
  • if petechial/purpuric rash
    • see meningococcal septicaemia
  • if febrile neutropenia or immunocompromised then:¹⁾
    • cefepime 2 g (child: 50 mg/kg up to 2 g) IV, 8-hourly, OR,
    • ceftazidime 2 g (child: 50 mg/kg up to 2 g) IV, 8-hourly, OR,
    • Tazocin (piperacillin + tazobactam) 4+0.5 g (child: 100+12.5 mg/kg up to 4+0.5 g) IV, 8-hourly
    • add vancomycin if either:
      • is in shock
      • known to have MRSA
      • has clinical evidence of a catheter-related infection in a unit with a high incidence of MRSA infection
      • not responding by 48hrs
  • if there is pain on moving muscles in context of sepsis - contact plastics or surgery ASAP to consider necrotising fasciitis or myositis whilst awaiting CT scan
  • empiric antibiotics in adults if Pseudomonas is unlikely:
    • vancomycin, PLUS, EITHER
      • ceftriaxone, OR,
      • ticarcillin-clavulanate, OR,
      • imipenem or meropenem
  • empiric antibiotics in adults if Pseudomonas IS likely:
    • vancomycin, PLUS, TWO OF EITHER
      • antipseudomonal cephalosporin (eg, ceftazidime, cefepime) OR
      • imipenem or meropenem, OR,
      • ticarcillin-clavulanate, OR,
      • ciprofloxacin, OR,
      • gentamicin, OR
      • a monobactam
• urinary catheter and sent CSU m/c/s, monitor fluid balance
• CXR
• blood transfusion if Hb < 7
• repeat lactate after 1hr Rx

• severe sepsis, plus, either:
  • systolic BP < 90, MAP < 65 or repeat lactate > 4 after initial iv bolus. or,
  • initial lactate > 4 and repeat lactate after initial iv bolus still > 2

• decide if patient will be suitable for ICU care, and if so, then proceed with critical care Mx as below.
• discuss with critical care team early and seek ICU/HDU bed
• this assumes initial Mx in 1st hours as for severe sepsis has been completed
• Rx targets:
  • CVP 8-12mmHg
  • mean arterial pressure ≥ 65mmHg
  • urine output ≥ 0.5 mL/kg/hr
  • central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively
  • normalisation of serum lactate levels
  • source of infection controlled
• consider inserting central venous line if not already placed, and no C/I
  • no benefit of routine CVC insertion ²⁾
• insert arterial line if not already placed
• control source of infection
  • remove any infected catheter or device
  • if no source of infection is evident then urgent CT scans of chest, abdo, and pelvis should be strongly considered ASAP, without contrast if administration of contrast will either delay CT or cause issues with nephrotoxicity. The risk of radiation from having to perform repeat scans with contrast at a later time is far outweighed by the risk of occult surgical sepsis or bowel ischaemia not being detected early.
  • if abscess or pus is detected, arrange for drainage
    • when infected peripancreatic necrosis is identified as a potential source of infection, definitive intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred³⁾
    • the effective intervention associated with the least physiologic insult should be used (eg, percutaneous rather than surgical drainage of an abscess)
• iv crystalloid boluses of 500-1000ml to maintain CVP 8-12mmHg
• if CVP adequate but MAP < 65mmHg, and patient suitable for ICU, then:
  • commence noradrenaline / norepinephrine infusion
    • NB. adrenaline is not used as initial single agent as it has a higher likelihood of impairing splanchnic blood flow and tissue perfusion
    • NB. dopamine may have some benefits over noradrenaline for those with hypoperfusion of the extremities (“cold sepsis”) but as it has more adverse effects and it is more likely to fail as a single agent, noradrenaline is still a reasonable choice⁴⁾
    • NB. vasopressin may be a useful 2nd line agent
    • NB. phenylephrine may be useful when tachycardias and arrhythmias preclude use of agents with beta-adrenergic activity such as noradrenaline
  • if central venous oxygen saturation < 70% despite Hb > 7, and adequate CVP and MAP, then:
    • consider commencing dobutamine infusion
• iv dexamethasone 0.15mg/kg to max 10mg qid or hydrocortisone 50mg iv qid for 5-7 days
  • starting within 8hrs of onset of shock if severe septic shock (defined as a systolic blood pressure <90 mmHg for more than one hour despite both adequate fluid resuscitation and vasopressor administration)⁵⁾
  • NB. appears to be no added benefit of also using fludrocortisone