Guideline for the management of pyrexia in critically ill patients

Temp >38

  • Physical exam (lines, wounds, pressure areas, chest, abdo, DVT)
  • Blood and sputum cultures
  • CXR if any respiratory signs
  • Urine culture only if urinary tract manipulation, stones, obstruction, neutropenia
  • C-diff test if diarrhoea (other organisms only if immunocompromised)
Temp >38 but <39
  • Await culture results
  • or
  • Broad spectrum ABX immediately after cultures if obvious source infection or neutropenia or clinical deterioration (hypoxia, ↑RR, ↑HR, ↓ compliance, hypotension, confusion, oliguria, ↑ lactate, ↑WBC/CRP, ↓ PLT, worsening coagulopathy)
Temp >39 or persistent fever after 48h or clinical deterioration
  • Urine culture
  • Change central lines >48h old
  • Consider CT/US scan of sinuses and removal of nasal tubes
  • Broad spectrum ABX
Re-evaluate after 48h
Consider:
  • CT abdo esp if risk of abdominal sepsis (abdo surgery, distension, tenderness, not absorbing feed)
  • Antifungals if fever persists despite empiric ABX and no source identified (risk factors - >10days ICU, multiple broad spectrum ABX, immunocompromise)
  • Other tests include venography (DVT) and differential WBC for eosinophils (hypersensitivity reaction)
  • Stop or change any new drugs if possible.
Do not give paracetamol or externally cool patients for fever unless brain injury, cardiac arrest, temp >40 or critical ischaemic heart disease.

Rationale for guideline:

Pathogenesis
Monocytes release cytokines (esp IL 1,6 and TNF)
Bind to specific receptors in the hypothalamus
Activates phospholipase A2 which convert membrane phospholipids to arachidonic acid which is converted to endoperoxidases via COX then forms PGE2
This diffuses across the BBB to inhibit warmth receptors so activating responses designed to increase heat production and decrease loss

Pros
Pyrexia enhances immune function including antibody production, T-cell activation, cytokine production and enhanced neutrophil and macrophage function.
Some pathogens such as strep pneumoniae are inhibited by pyrexia.
Increased temp is associated with improved outcome from infectious diseases and also increases resistance to infection.

Cons
CO, O2 consumption, CO2 production, and energy expenditure all increase.
O2 consumption increases by 10% for each 1 degree increase in temp.
Cerebral metabolic rate decreases 7% for each 1 degree reduction in temp.
This is detrimental in patients with brain injury and limited cardiorespiratory reserve.
Children can get febrile convulsions.

Definitions and measurement
Pulmonary artery thermistor is the gold standard for core temp.
Bladder and lower 2/3 oesophagus are virtually as good.
Rectal, oral and tympanic IR are the next best in order or decreasing accuracy.
Other methods like axillary measurement are not recommended.
Normal temp is 37 with diurnal variation of up to 1 either way.
Pyrexia defined as >38.3 (Society of Critical Care Medicine) – this number chosen as 101F so 38 may be just as appropriate.

Patterns
Fever pattern usually not useful for diagnosis.
Clues from timing ie 48h post intubation may be VAP, 5-7 days post-op may be abscess formation and fever 10-14 days after ABX may be fungal infection.

Causes

Anything initiating cytokine release can cause pyrexia (and leucocytosis).
WBC/CRP/pyrexia are non specific. Procalcitonin better (not increased by viral infection, surgery or chronic inflam states).
Infections are the commonest cause in ICU but other causes common.
Non-infectious causes usually result in a temp of < 39.
Temps above this should be assumed to be infectious.
Features of sepsis should be looked for.

Non-infectious causes

RS - Aspiration pneumonitis, ARDS, fat embolus, PE
GI - Pancreatitis, acalculous cholecysitis, ischaemic bowel
CVS - MI
CNS - damage to CNS (eg SAH) or ANS
Musculoskeletal
  • Surgery (up to 72h post-op)
  • Trauma
  • DVT
  • Compartment syndrome
Drugs
  • Hypersensitivity - Common causes of drug fever are beta-lactams and phenytoin. Pyrexia can persist for up to 7 days after stopping drug. Eosinophils may be raised but often not. Blood transfusion.
  • Withdrawal - alcohol, opiates
  • Serotonin syndrome (SSRI + linezolid or tramadol), Neuroleptic malignant syndrome (haloperidol)
  • Altered thermoregulation
Acalculous cholecysitis
Occurs in 1.5% of critically ill patients and is caused by gallbladder ischemia, bile stasis in the absence of stimuli for emptying of the gallbladder, PEEP and parenteral nutrition.
Can progress to gangrene and perforation.
Causes abdominal pain (RUQ) and SIRS.
Diagnosis by clinical signs (requires an awake patient),US (wall thickness >3mm) and CT both with high sensitivity but low specificity (GB wall thickening is very common in the critically ill secondary to fluid overload).
Management is percutaneous cholecystostomy (drainage).

Infectious causes

VAP
Sinusitis
Blood stream infection
Catheter related infection
C-diff diarrhoea
Abdominal infection
Wound infection

VAP
Occurs in 25% intubated patients.
Risk reduced by head up positioning and increased by antacids.
Initial empiric ABX must be broad and cover both gram +ve and –ve orgs.
Sampling of lower respiratory tract secretions allows safe discontinuation of ABX in culture –ve patients.

Sinusitis
Result of obstruction of sinuses.
Common if nasal intubation.
Risk also from NGTs and max fax trauma.
Less common than other nosocomial infections.
Purulent discharge in 25% other wise clinically silent.
Diagnosis requires CT or US.
Maxillary sinus most commonly involved.
Infection only present in 40% of those with radiologic abnormalities.
Treatment is removal of nasal tubes, ABX, sinus drainage if does not respond to ABX
2/3 gram –ve (most pseudomonas).

Catheter related infection
20% of central venous catheters become colonised.
Incidence of blood stream infection is 2-5/1000 catheter days.
Arterial and PIC lines 2-3/1000.
Tunneled lines 0.2-1/1000.
Venflons <0.1/1000.
Coag -ve staph most common followed by Staph aureus, enterococci and gram -ves.
Risk increases with length of time, number of ports and the number of manipulations.
Subclavian lines get infected < jugular < femoral .
Replacement of a colonised catheter over a guidewire is associated with rapid recolonisation.
Antiseptic or antimicrobial coatings may be the best method of prevention (assuming strict aseptic placement).

Urinary tract infection
Colonic flora rapidly colonise urinary catheters.
Bacteruria from catheterised patients is very common (30% of hospitalised patients) and implies colonisation rather than infection.
<3% of patients with bacteruria will develop bacteraemia from the same organisms.
Risks for infection are urinary tract manipulation or surgery, kidney stones, obstruction, neutropenia.
Dipstick testing is not recommended as low sensitivity and specificity.
Urine culture included in screen of pyrexia but results should be interpreted with caution.

C-diff
20% of hospitalised patients become infected 1/3 of which develop diarrhoea.
Symptoms usually begin during or soon after a course of ABX.
Causes abdominal pain and distension, SIRS and profuse diarrhoea.
If severe causes pseudomembranous colitis.
Must test for toxins A and B.
Glutamate dehydrogenase has a negative predictive value >99%.

Candida
17% of nosocomial ICU infections due to fungi.
Should be considered in all patients who have been in the ICU for >10 days and have received multiple courses of ABX.
Particularly important pathogen in those with ongoing peritonitis.
Most ICU patients become colonised with candida soon after admission.
Non-neutropenic patients with candida in sputum or urine are unlikely to have invasive candidiasis.
Need identification from sterile specimens (BAL, pleural fluid etc).

Other infections
Nosocomial meningitis extremely rare so LP and CT not necessary unless focal neurology or CNS instrumentation.
Otherwise unexplained pyrexia post abdominal surgery should prompt an abdo CT.
Wound infections – incidence 3%. Inspect surgical wounds daily. If suspect infection than open wound and culture (superficial swabs pointless as will be contaminated by skin commensals). No evidence for ABX for wound infections without systemic infection.
Pressure sores.
Retained tampons.

Blood cultures
Indicated in all febrile patients.
Minimum of 2 should be taken.
Colonisation of venous catheters can give misleading results (colonisation of line rather than blood stream infection) but is acceptable if lines are less than 3 days old. Use distal port of central line. CRBSI confirmed by growing same org from catheter and blood.
Practically take 1 venous sample and 1 from A-line or central line <3 days old.
Volume of blood is the single most important factor for the sensitivity of BCs – 20mls preferable; minimum 10.

Sputum culture
Should be lower airway - deep tracheal or BAL/PSB.
Need to be in lab <2h after sample taken.
Quantitative counts more useful (>106 orgs good PPV).

Stool culture
Only C-diff necessary for diarrhoea if - not present on admission, not immunocompromised.

Treatment of pyrexia

Pyrexia helps host defence and is hostile to many pathogens.
It is also an important sign and allows monitoring of response to treatment.
Acute hepatitis may occur if regular paracetamol given to patients with reduced glutathione reserves (alcoholics, malnourished etc).
So routine treatment not recommended.
Treat if
  • Brain injury
  • Post cardiac arrest
  • Severely limited cardiovascular reserve
  • Temp >40
External cooling
No more effective than paracetamol.
Causes temperature fluctuations and rebound hyperthermia.
Pyrexial patients have an altered hypothalamic set point so patient already responding as if cold. Cooling will then just result in greater physiological effort to maintain temp with ↑ metabolism, O2 consumption (active cooling ↑ it 40%), CO2 production etc.

References

Fever in the ICU Paul E. Marik Chest 2000;117;855-869

Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America O’grady et al. Crit Care Med 2008 Vol. 36, No. 4