The earth might be warming up and so might our patients in the ICU. It is easy to fall into the Fever ➝ CRP ➝ antibiotics trap, but our goal is to be more responsible.
- Raised temperature: fever vs. hyperthermia
- Central fever
- Stroke and fever
- Temperature management strategies for stroke
- Infectious causes of fever
- Noninfectious causes of fever
might be fever or hyperthermia.
Fever is more common and defined by a raised hypothalamic setpoint, due to
- infectious or
- other inflammatory reasons, or due to
- central stimulation
of the hypothalamus (“central fever”, e.g. blood in brain, see below). Note that CRP does not really distinguish between the three causes of fever, while procalcitonin might at least hint at an infectious etiology. Also there is no proper consensus as to what constitutes fever.
Non-fever hyperthermia is failure of heat regulation with intact setpoint, e.g. in exsiccosis. Typically, antipyretics are ineffective in pure hyperthermia.
Fever control in the ICU has been studied, if not extensively, and never been shown to be helpful. Most recently, Acetaminophen was not effectively in improving anything (Young NEJM 2015). It may be harmful, especially in septic patients (see Schulman 2005 and Lee 2012).
(see this 2016 review on the subject) is always suspected in neuro patients, but hard to prove.
Pathophysiology, it is due to damage to the hypothalamus or contact of this structure to blood 0r pus (this can be reproduced in animals). In brain injury, diffuse axonal damage and frontal lesions indicate shear stress on the hypothalamus and correlate with central fever.
Clinically, central fever might have less diaphoresis and tachycardia, but this is not very specific. The diagnosis relies on exclusion of other infectious and inflammatory causes. The literature (Predicting central fever in NICU, Hocker 2013) says
The combination of negative cultures; absence of infiltrate on chest radiographs; diagnosis of subarachnoid hemorrhage, intraventricular hemorrhage, or tumor; and onset of fever within 72 hours of admission predicted central fever with a probability of .90.
Therapywise, central fever is harder to treat, so that physical measures and endovascular cooling are often employed. I grew up with the lytic cocktail (blocking every neurotransmitter you know), but there is no proper literature on that.
You should bear in mind that there is another central neurologic complication with fever that complicates severe brain injury, namely paroxysmal sympathetic hyperactivity – this is a chapter on its own.
Stroke and fever
- Very common: (40-61%) in the first 2d of stroke have elevated temperatures, depending on the definition
- Very bad: Raised temperature correlates with bad outcome, both in animal experiments (40° x 3h leads to 3 times the stroke volume) and patients (e.g., Greer 2008).
- Early is worse: Stroke is more vulnerable to fever in the first 24 hours – it accelerates the conversion of penumbra to stroke and all bad pathophysiologic cascades (apoptosis, inflammatory).
- Can be controlled: Fever control is feasible in principle and regarded as one of the active components of stroke unit care.
Temperature management strategies for stroke
- Hypothermia: Bi 2011, de Georgia 2004, Ictus-L 2006, Ovesen 2013 show no benefit
EuroHyp-I (ongoing), Ictus 2/3 (terminated; no results yet) – endovascular methods, no evidence (but very effective)
- antipyretics: PAIS (den Hertog 2009), PISA (Dippel 2003) – only modest effect on temperature, no benefit (NRO, survival)
- antibiotics: EPIAS, PANTHERIS – reduced infection rates, no benefit (NRO, survival)
- Fever treatment: blankets/air cooling probably not better than drugs, endovascular highly effective – no benefit shown
QASC trial shows that the combination of controlling fever, dysphagia and glucose is beneficial
Infectious causes of fever
- Head: meningitis/encephalitis, brain abscess, ventriculitis, sinusitis, dental, HEENT (including epiglottitis)
- Circulatory: CVC, endocarditis/myocarditis, peripheral cannula, aortitis, mediastinitis
- Respiratory: pneumonia/bronchitis, empyema, VAP
- GI: esophagitis, pancreatitis, diverticulitis, rectal/anal abscess, C. diff
- Urogenital: prostatitis, pyelonephritis, cystitis, PID
- Hematological: malaria, HIV
- Integument: Osteomyelitis, cellulitis, fasciitis, myositis
Noninfectious causes of fever
- Vascular: stroke, IVH, ICH, SAH, MI, ischemic bowel, DVT
- Idiopathic inflammatory: Gout, postoperative, acalculous cholecystitis, pancreatitis, aspiration pneumonitis, GI bleed, ARDS
- Traumatic: Hematoma, Ulcers
- Drug fever: high spiking fever, chills, maybe leucocytosis, eosinophilia; drugs are beta-lactams, PHE, iv contrast
- Malignant neuroleptic syndrome, Serotonin syndrome (beware: linezolid, MCP, setrons), malignant hyperthermia
- Autoimmune: vasculitis, hemolysis, transplant rejection, transfusion
- Psychiatric: Withdrawal
- Neoplastic: renal cell CA, tumor lysis, lymphoma, leucemia
- Endocrine: Ovulation, Thyroiditis, Thyreotoxicosis, adrenal insufficiency
- Wrotek. Treatment of fever after stroke. Pharmacotherapy 2011
- Ntaios. ESO guidelines for the management of temperature in patients with acute ischemic stroke. Int J Stroke 2015