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Question 3#

A 32-year-old man presents to the ICU after coiling of the anterior communicating artery aneurysm for subarachnoid hemorrhage. He is placed on cefazolin for external ventricular drain prophylaxis. On the sixth postoperative day he develops frequent loose stools and a temperature of 38.8°C.

Which of the following is INCORRECT regarding fever?

a. Early administration of acetaminophen to treat fever due to probable infection reduces the number of ICU-free days
b. Fever may enhance immune cell function, inhibit pathogen growth, and increase the activity of antimicrobial drugs
c. The ability to develop fever in older adults is impaired, and baseline temperature in older adults is lower than in younger adults
d. For every increase of one degree above 37°C, there is a 13% increase in O2 consumption
e. Acetaminophen is oxidized in the brain by the p450 cytochrome system, and the oxidized form inhibits cyclooxygenase activity

Correct Answer is A

Comment:

Correct Answer: A

Early administration of acetaminophen to treat fever due to probable infection does not affect the number of ICU-free days. A study published in 2015 by Young et al randomized febrile ICU patients with known or suspected infection to receive 1 g intravenous acetaminophen or placebo every 6 hours until discharge, fever resolution, antibiotic discontinuation, or death. Primary outcome was ICU-free days from randomization to day 28. There was no significant difference between groups. Despite this, there is evidence to support that early treatment of fever leads to reduction of vasopressor dose and reduced mortality in septic patients requiring mechanical ventilation.

Fever has many pathophysiologic effects including increased oxygen consumption (D), enhanced immune function, increased antimicrobial activity, and decreased pathogen growth (B). Older adults have a lower baseline temperature and impaired ability to develop fever (C). Acetaminophen is the mainstay of therapy and works by inhibiting cyclooxygenase. The oxidized form is active in the brain after metabolization by the p450 system (E).

References:

  1. Dinarello CA. Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. J Endotoxin Res. 2004;10:201.
  2. Flower RJ, Vane JR. Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-acetamidophenol). Nature. 1972;240:410.
  3. Young P, Saxena M, Bellomo R, et al. Acetaminophen for fever in critically ill patients with suspected infection. N Engl J Med. 2015;373:2215-2224.