The hypothalamus controls body temperature through neurons that receive signals from temperature receptors in the skin and blood. These signals are integrated in the hypothalamus' temperature regulation center to maintain a normal temperature of around 37°C. Fever is defined as a temperature greater than 37.2°C in the morning or 37.7°C in the afternoon. Common causes of fever in the ICU include infections like ventilator-associated pneumonia as well as non-infectious causes like drug reactions. Blood cultures, sputum cultures, urine cultures and imaging tests may help diagnose the cause, and treatment is aimed at the underlying condition.

1. BY
DR MUHAMMAD AKRAM
M.C.H.JEDDAH

2. PHYSIOLOGY
• Body temperature is controlled by the
hypothalamus
• Neurons in pre-optic ant hypothal & post
hypothal
• Receive two kinds of signals
• Peripheral N transmit info from warmth/cold receptors
of skin
• Other from temp of blood bathing the region
• Both signals are integrated by Temp
Regulation Centre (TRC) of hypothalamus
• Maintain normal temp
• In neutral temp environment
• Humans produces more heat than is needed
• To maintain core body temp at 37°C
2

3. TEMPERATURE
MEASUREMENT
 Mean oral temp = 36.8° ± 0.4°C (98.2°
± 0.7°F)
 Lowest at 6 A.M. and highest between 4 to
6 PM
 Maximum normal oral temp
 37.2°C (98.9°F) at 6 AM
 37.7°C (99.9°F) at 4 PM (99 %)
 Fever Definition ( Harrison)
 A.M temperature of >37.2°C (>98.9°F) or
 P.M. temperature of >37.7°C (>99.9°F)
3

4. TEMPERATURE
MEASUREMENT
 Normal daily temp variation is 0.5°C (0.9-
1°F)
 During febrile illness diurnal variation is
higher
 Daily temp variation is fixed in early
childhood
 Elderly individuals have reduced ability to
develop fever even in severe infections
 Rectal temp 0.4°C (0.7°F) > oral readings
 Lower-esophageal temp reflects core temp

5. TEMPERATURE
MEASUREMENT
 Tympanic membrane (TM)
thermometer
 Measure radiant heat from TM & ear canal
 TM values are 0.8°C (1.6°F) < rectal
temp
 In women who menstruate AM temp
lower in the 2 weeks before ovulation
 It rises by ~0.6°C (1°F) with ovulation
 Remains at that level until menses occur

6. DEFFINITION OF FEVER IN
ICU
 The Society of Critical Care
Medicine practice parameters
define fever in the ICU as
 a temperature > 38.3°C (
101°F).Unless the patient has other
features of an infectious process,
 only a temperature > 38.3°C (
101°F) warrants further
investigation.

7. EPIDEMIOLOGY
 Fever complicates up to 70 percent of all ICU
admissions and is often due to an infection
 In one observational study of 24,204 adult ICU
admissions, fever ≥39.5ºC (103 ºF) was associated
with an increase in mortality (20 versus 12 percent)

8. FEVER PATTERNS
 Most patients have remittent or intermittent
fever that, when due to infection, usually follow
a diurnal variation.
 Sustained fevers have been reported in
patients with Gram-negative pneumonia or CNS
damage.
 The appearance of fever at different time points
in the course of a patient’s illness may however
provide some diagnostic clues.
 Fevers that arise > 48 h after institution of
mechanical ventilation may be secondary to a
developing pneumonia.
 Fevers that arise 5 to 7 days postoperatively may be
related to abscess formation.
 Fevers that arise 10 to 14 days post institution of
antibiotics for intra-abdominal abscess may be due to
fungal infections.

9. CAUSES OF FEVER IN THE ICU
 Any disease process that results in the release of the
proinflammatory cytokines IL-1, IL-6, and TNF- will
result in the development of fever
 Infections are the commonest cause of fever in ICU
patients, many noninfectious inflammatory
conditions cause the release of the proinflammatory
cytokines with a febrile response.
 Similarly, it is important to appreciate that not all
patients with infections are febrile.
 Approximately 10% of septic patients are hypothermic
and 35% are normothermic at presentation.
 Septic patients who fail to develop a temperature have a
significantly higher mortality than febrile septic patients
The reason that patients with established infections fail
to develop a febrile response is unclear; however,
preliminary evidence suggests that this aberrant
response is not due to diminished cytokine production.

11. DIFFERENTIAL DIAGNOSIS
 Sources of fever in the ICU may be
 Infectious
 Non infectious

13. NONINFECTIOUS CAUSES
 For reasons that are not entirely clear, most noninfectious
disorders usually do not lead to a fever > 38.9°C (102°F);
therefore, if the temperature increases above this
threshold, the patient should be considered to have an
infectious etiology as the cause of the fever.
 However, patients with drug fever may have a temperature
> 102°F.
 Similarly, fever secondary to blood transfusion may be >
102°F.
 On the basis of the number of medications administered to
patients in the ICU, one would expect drug fever to be a
relatively common event.
 Drug fever should be considered in patients with an
otherwise unexplained fever, particularly if they are
receiving ß-lactam antibiotics.
 Drug fever is usually characterized by high spiking
temperatures and shaking chills. It may be associated with
a with leukocytosis and eosinophilia. Relative bradycardia,
although commonly cited, is uncommon.

14. NONINFECTIOUS CAUSES
 ATELECTASIS is commonly implicated as a
cause of fever. Standard ICU texts list
atelectasis as a cause of fever, although
they provide no primary source.
 FEBRILE REACTIONS
 complicate about 0.5% of blood transfusions
 More common following platelet transfusion.
 Antibodies against membrane antigens of
transfused leukocytes and/or platelets are
responsible for most febrile reactions to cellular
blood components.
 Febrile reactions usually begin within 30 min to 2
h after a blood-product transfusion is begun.
 The fever generally lasts between 2 h and 24 h
and may be preceded by chills.
 An acute leucocytosis lasting up to 12 h
commonly occurs following a blood transfusion.

15. NONINFECTIOUS CAUSES
 ARDS may progress to a "chronic" stage characterized
by pulmonary fibroproliferation and fevers
 ACALCULOUS CHOLECYSTIS occurs in approximately
1.5% of critically ill patients. An important
"noninfectious" cause of fever in critically ill patients, as
it is frequently unrecognized and therefore potentially
life threatening
 The pathophysiology of acalculous cholecystitis is related
to the complex interplay of a number of pathogenetic
mechanisms, including gallbladder ischemia, bile stasis with
inpissation in the absence of stimuli for emptying of the
gallbladder, positive-end expiratory pressure, and
parenteral nutrition.
 Bacterial invasion of the gallbladder appears to be a
secondary phenomenon.
 The diagnosis of acalculous cholecystitis is often
exceedingly difficult and requires a high index of suspicion.
 Pain in the right upper quadrant is the finding that most
often leads the clinician to the correct diagnosis, but it may
frequently be absent.

16. NONINFECTIOUS CAUSES
 The most difficult patients are those recovering from
abdominal sepsis who deteriorate again, misleadingly
suggesting a flare-up of the original infection.
 Rapid diagnosis is essential because ischemia may
progress rapidly to gangrene and perforation, with
attendant increase in the already high morbidity and
mortality
 The diagnosis should therefore be considered in every
critically ill patient who has clinical findings of sepsis
with no obvious source
 Ultrasound is the most common radiologic investigation
used in the diagnosis of acalculous cholecystitis
 Features include increased wall thickness, intramural
lucencies, gallbladder distension, pericholecystic fluid,
and intramural sludge. Wall thickness 3 mm is reported
to be the most important diagnostic feature on
ultrasound examination, with a specificity of 90% and a
sensitivity of 100%.
 Percutaneous cholecystostomy may be the procedure of
choice
 Posterative fever upto 48 Hrs.

18. VENTILATOR-ASSOCIATED
PNEUMONIA
 occurs in approximately 25% of
patients undergoing mechanical
ventilation
 Fagon and colleagues reported an
attributable mortality of 27%.
 Diagnosis of VAP remains one of the
most difficult clinical dilemmas in
critically ill patients receiving
mechanical ventilation
 initial empiric antibiotic regimen must
be broad and cover both Gram-
positive and negative organisms,

19. DIAGNOSTIC APPROACH
 A thorough review of the medical history and a full physical
examination should be performed whenever a patient develops
an unexplained fever in the ICU.
 Blood cultures are the only mandatory diagnostic tests in patients
with a new fever
 SPUTUM..
 indicated for febrile patients with any of the following findings
 new sputum production; a change in the color, amount, or
thickness of their sputum.
 a new or progressive pulmonary infiltrate.
 an increased respiratory rate.
 an increased minute volume; a decreased tidal volume;
decreased oxygenation.
 needing more ventilatory support; or requiring more inspired
oxygen.

20. DIAGNOSTIC APPROACH
 URINE .
 Urinalysis and urine culture are
indicated for febrile patients with
○ a urethral catheter.
○ urinary obstruction.
○ renal calculi.
○ recent genitourinary surgery or trauma,
or neutropenia.

21. DIAGNOSTIC APPROACH
 CHEST IMAGING
 A chest radiograph is worthwhile in
many patients with
 respiratory symptoms or signs.
 It may detect a new or progressive
pulmonary infiltrate.
 distinguish pneumonia from
tracheobronchitis, or identify a respiratory
source of fever other than pneumonia or
tracheobronchitis
 Computed tomography (CT) should be
reserved for the clarification of abnormal
chest radiographic findings.

22. DIAGNOSTIC APPROACH
 S.CHEMISTRY
 Done for LFT, Urine fucntions,
electrolyte imbalance
 TFT(THYROID FUCTION TEST)
 Done if thyroid storm is suspected

24. Blood Cultures
 B/C should be obtained in patients with a new fever
when clinical evaluation does not strongly suggest a
noninfectious cause
Skin Preparation
 The site of venipuncture should be cleaned with either
2% chlorhexidine gluconate in 70% isopropyl alcohol
(2% alcoholic chlorhexidine), or 1–2% tincture of iodine
(iodine in alcohol). Povidone iodine (10%), although
acceptable, is a less efficient agent.
 When blood is to be inoculated into a culture or
transport tube, the needle used for venipuncture should
not be replaced by a sterile needle. The risk of a needle
stick injury during the switch in needles is currently
thought to outweigh the risk of contamination

25. Blood Cultures
Blood Volume and Collection System
 One blood culture is defined as a sample of 20–30
mL of blood drawn at a single time from a single
site, regardless of how many bottles or tubes the
laboratory may use to process the specimen.
 The sensitivity of B/C → obtaining the cultures
before the initia-tion of anti-infective therapy and
the volume of blood drawn

26. Blood Cultures
Number of Cultures and Sites
 3-4 B/C with adequate volume (20–30 mL each) are
drawn within the first 24 hrs of suspected bacteremia
or fungemia
 Each culture should be drawn by separate venipuncture
or through a separate intravascular device but not
through multiple ports of the same intravascular
catheter
 There is no evidence that the yield of cultures drawn
from an artery is different from the yield of cultures
drawn from a vein.
 Culture from the device (+) and from venipuncture (-);
the positive culture may represent a contaminant or a
catheter-related infection, but clinical judgment rather
than any rigid criteria is needed to interpret the
significance of discordant results

27. Blood Cultures
Labeling
 Blood cultures should be clearly
labeled with the exact time, date,
and anatomic site or catheter lumen
from which blood is drawn and also
include other information
(concomitant antimicrobial therapy)
that may be appropriate.

28. Recommendations for
Obtaining
Blood Cultures
 1. 3-4 B/C within the first 24 hrs of the onset of fever
(level 2)
 2. Additional B/Cx2: suspicion of continuing or
recurrent bacteremia or fungemia or 48–96 hrs after
initiation of appropriate therapy for
bacteremia/fungemia. (level 2).
 3. P’ts without an indwelling vascular catheter, obtain
at least two blood cultures using strict aseptic
technique from peripheral sites by separate
venipunctures after appropriate disinfection of the skin
(level 2).
 4. 2% chlorhexidine gluconate in 70% isopropyl alcohol,
but tincture of iodine is equally effective. 30 secs of
drying time before proceeding with the culture
procedure. Povidone iodine is an acceptable alternative,
but it must be allowed to dry for 2 mins (level 1)

29. Recommendations for
Obtaining
Blood Cultures
 5. The injection port of the blood culture bottles should
be wiped with 70–90% alcohol before injecting the
blood sample into the bottle to reduce the risk of
introduced contamination (level 3)
 6. P’t with intravascular catheter→one B/C from
venipuncture and at least one culture from
intravascular catheter. Obtaining blood cultures
exclusively through intravascular catheters yields
slightly less precise information than information
obtained when at least one culture is drawn by
venipuncture (level 2).
 7. Label the blood culture with the exact time, date,
and anatomic site from which it was taken (level 2).
 8. Draw 20–30 mL of blood per culture (level 2).

30. Fever diagnostic algorithm
Marik, P. E. Chest 2000;117:855-869

31. REFERRENCES
 Critical Care medicine 2008
 UPtoDate 2012
 Harrison book of Medicine
 Guidelines for evaluation of new fever in critically ill
adult patients: 2008 update from the American
College of Critical Care Medicine and the Infectious
Disease Society of America.