What is the cause of fever in intracranial hemorrhage (ICH), central versus infectious?

Causes of Fever in Intracerebral Hemorrhage: Central vs. Infectious

Fever in intracerebral hemorrhage (ICH) is most commonly central (non-infectious) in origin, occurring in approximately 71% of febrile ICH patients, while infectious causes account for only about 29% of cases. 1

Mechanisms and Prevalence of Fever in ICH

Central (Non-infectious) Fever

• Central fever is the predominant cause of temperature elevation in ICH patients and is associated with:
  • Direct damage to temperature-regulating centers in the brain
  • Intraventricular hemorrhage (IVH) - strongly associated with fever development 2, 1
  • Increased intracranial pressure (ICP) - fever is associated with increases in intracranial volume homeostasis 2
  • Blood volume in the brain parenchyma - larger ICH volumes correlate with higher fever risk 1
  • Inflammatory response to blood breakdown products

Infectious Fever

• Less common but important to identify as it requires specific treatment
• Common infectious sources in ICH patients include:
  • Pneumonia (5.6% of ICH patients) 2
  • Aspiration (2.6%) 2
  • Urinary tract infections
  • Bacteremia
  • Sepsis (1.7%) 2

Distinguishing Features

Factors Associated with Central Fever

• Occurs early in the course of ICH
• Associated with:
  • Larger ICH volume (OR = 1.01, P = .04) 1
  • Presence of intraventricular hemorrhage (OR = 2.0, P = .03) 1
  • External ventricular drain placement (OR = 3.7, P < .0001) 1
  • Surgical evacuation (OR = 6.78, P < .0001) 1
• Higher in-hospital mortality compared to infectious fever 1
• May be resistant to conventional antipyretics 3
• May resolve with CSF diversion in cases of acute hydrocephalus 3

Factors Associated with Infectious Fever

• Often develops later in the hospital course
• Associated with:
  • Longer length of hospital stay 1
  • Positive microbial cultures 1
  • Elevated procalcitonin levels (PCT) - significantly higher in patients with definite infection compared to no infection 4

Clinical Implications

Impact on Outcomes

• Fever worsens outcomes in ICH regardless of etiology 2
• In patients surviving the first 72 hours after hospital admission, the duration of fever is related to outcome and appears to be an independent prognostic factor 2
• Non-infectious fever is associated with higher in-hospital mortality 1
• Infectious fever is associated with longer hospital stays 1

Management Recommendations

• Aggressive treatment of fever to normal levels is recommended in patients with ICH (Class I, Level of Evidence C) 2
• Sources of fever should be identified and treated 2
• Antipyretic medications should be administered to lower temperature in febrile patients with stroke 2
• Procalcitonin testing may help differentiate between infectious and non-infectious causes 4
• Monitoring and management of ICH patients with fever should take place in an intensive care unit setting (Class I, Level of Evidence B) 2, 5

Pitfalls and Caveats

• Extensive testing for infectious sources is often performed in ICH patients with fever, only to conclude that the fever is "central" in origin 6
• Fever can persist for extended periods (1-40 days) in ICH patients 6
• The relationship between fever and outcomes in ICH remains somewhat ambiguous, with some studies showing increased mortality but not necessarily worse functional outcomes among survivors 7
• Treating the underlying cause (such as CSF diversion for hydrocephalus) may be more effective than antipyretics alone in cases of central fever 3