PETRUS IRIANTO

BAGIAN PENYAKIT DALAM

RSUD DOK II JAYAPURA

Fever is an elevation of body

temperature that exceeds the

normal daily variation, in
conjunction with an increase in
hypothalamic set point,
infectious causes are common

Core Temperature
Aortic blood temperature
Esophageal temperature
Tympanic membrane temperature

Clinical Approximates
Sublingual (oral) temperature
Axillary temperature
Rectal temperature

= 0.7o F < core

= 1.8o F < core
= 0.9o F > core

 Hyperthermia
An unchanged setting of the hypothalamic set point in conjunction

with an uncontrolled increase in body temperature that exceeds the

bodys ability to lose heat

Heat stroke

Thermoregulatory failure in association with a warm environment

Malignant hyperthermia
Hyperthermic and systemic response to halothane and other inhalational

anesthetics in patients with genetic abnormality

- Neuroleptic malignant syndrome

Syndrome of hyperthermia, autonomic dysregulation, and

extrapyramidal side effects caused by neuroleptic agents (e.g.,

haloperidol)

Hyperpyrexia
Temperature >41.5C (>106.7F)
Can occur with severe infections, but more

commonly occurs with central nervous system

(CNS) hemorrhages or hyperthermia

. The normal daily temperature variation is typically

0.5C (0.9F).
The mean normal oral temperature is 36.8 0.4C
(98.2 0.7F), with low levels at 6 a.m. and high
levels at 46 p.m.
However, in some individuals recovering from a
febrile illness, daily variation can be as great as
1.0C.
During a febrile illness, diurnal variations are usually

maintained, but at higher levels.

 Rectal temperatures are generally 0.4C (0.7F)

higher than oral readings.

Lower oral readings are probably attributable

to mouth breathing, a particularly important
factor in patients with respiratory infections and
rapid breathing.
Lower-esophageal temperatures closely reflect core

temperature.

Tympanic thermometer measurements, although

convenient, may be more variable than directly

determined oral or rectal values.

 Afferent Sensing
Cold receptors > A delta fibers
Warm receptors > C fibers
Integrated in spinal cord and CNS > hypothalamus
Central Integration
20% each contribution from: skin, deep chest and
abdomen, spinal cord, CNS, hypothalamus
Skin input predominates behavioral responses
Cold and warm response thresholds only 0.4 apart
Efferent Responses
Behavioral (clothing, adjusting environment)
Response to heat: sweat, cutaneous dilation
Response to cold: digital vasoconstriction (agonism)
Nonshivering thermogenesis (agonism)
Shivering

Microbial structural components and toxins,

antigen-antibody complexes, complement
components, and probably other molecules (as
yet unidentified) are all capable of stimulating
leukocytes and endothelial cells to produce
pyrogenic cytokines, including:
Interleukin (IL)-1, IL-6, tumor necrosis factor,
interferon

These cytokines act on the hypothalamic endothelium

to elevate the thermoregulatory set point, thus
causing fever

Monocytes, tissue macrophages

Keratinocytes
Gingival epithelium
Corneal epithelium
Renal mesangial cells
Brain astrocytes
Vascular endothelium
Vascular smooth muscle
NK cells
Fibroblasts

Neutrophil function
Enhanced migration
Enhanced superoxide production

Mononuclear function
Enhanced interferon production
Enhanced interferon tumor and viral activity
Tcell proliferation

For each 1 C elevation of body temperature:

Metabolic rate increase 10-15%

Insensible water loss increase
300-500ml/m2/day
O2 consumption increase 13%
Heart rate increase 10-15/min

 Fever vs hyperthermia
It is important to distinguish between fever and

hyperthermia.
Hyperthermia can be rapidly fatal and
characteristically does not respond to antipyretics.
There is no rapid way to make this distinction.
Hyperthermia is often diagnosed on the basis of
events immediately preceding elevation of core
temperature.
Heat exposure
Treatment with drugs that interfere with
thermoregulation

In addition to clinical history, physical aspects of

some forms of hyperthermia may alert the clinician.
In heat-stroke syndromes and in the setting of drugs that
block sweating, the skin is hot but dry.
Antipyretics do not reduce elevated temperature in
hyperthermia.

In fever and hyperpyrexia, adequate doses

of aspirin or acetaminophen usually result
in some decrease in body temperature.

Temperature < 102 F

Fo

Temperature > 102

Acute cholecystitis
Cholangitis
Acute MI
Pericarditis
Simple phlebitis Pyophlebitis
Pulmonary emboli
Septic pulmonary emboli
Acute pancreatitis
Abscess/infected pseudocyst
Viral hepatitis (AE)
Leptospirosis/drug fever
Wound infection SubQ abscess/Strep., V. vulnificus
Gastrointestinal bleed Bowel infarction
Cystitis
Pyelonephritis
Atelectasis Pneumonia
Hematoma Infected hematoma

Central fever
Drug fever
Heat stroke
Malignant hyperthermia
Neuroleptic malignant syndrome
Malaria
Smallpox

Sustained (Continuous) Fever

Intermittent Fever (Hectic Fever)
Remittent Fever
Relapsing Fever:
Tertian Fever
Quartan Fever
Days of Fever Followed by a Several Days
Afebrile
Pel Ebstein Fever
Fever Every 21 Day

Central Nervous System

oC
oF
Consequences
41
105.8
Delerium, seizures
42
107.6
Coma, CNS damage
41.642.0
106.97.6 Death (critical thermal
max)*
Ox phos uncouples
Other Consequences
BMR 15% per 1oC
PR 15 bpm per 1oC
Muscle proteolysis for acute phase reactant
synthesis
Bone resorption > hypercalcuria

CNS lesions

Stroke, trauma, encephalitis

High cord transection
Autonomic neuropathy

Endocrine diseases

Pheochromocytoma
Thyrotoxicosis
Addisons disease

Skin Diseases

Ichthyosis
Absent sweat glands

NonInfectious Etiologies of Fever

Miscellaneous
Severe CHF
Malignant hyperthermia
Neuroleptic malignant syndrome
Vasculitides
Malignancies
Inflammatory bowel disease

Classic FUO
Nosocomial FUO
Neutropenic FUO
HIV-Associated FUO

Fever of 38.3 C or higher on several

occasions
Fever of more than 3 weeks
duration
Diagnosis uncertain, despite
appropriate investigations after at
least 3 outpatient visits or at least 3
days in hospital

Fever of 38.3 C or higher on several

occasions
Fever of more than 3 weeks
duration
Diagnosis uncertain, despite
appropriate investigations after at
least 3 outpatient visits or at least 3
days in hospital

Fever of 38.3 or higher on

several occasions
Neutrophil count is <500/mm3
or is expected to fall to that
level in 1 to 2 days
Failure to reach a diagnosis
despite 3 days of appropriate
investigation

Fever of 38.3 or higher on

several occasions
Fever of more than 3 weeks for
outpatients or more than 3 days
for hospitalized patients with
HIV infection
Failure to reach a diagnosis
despite 3days of appropriate
investigation

Acetaminophen is generally a first-line

antipyretic due to being well tolerated

with minimal side effects.
Pediatric dose: 10-15mg/kg q4-6h

(2400mg/day); adult: 650mg q 4

h(4000mg)
Can be hepatotoxic in high doses; can
upset stomach

The febrile response is a complex physiologic

reaction to disease involving a cytokine-mediated
rise in body temperature, generation of acutephase reactants, and activation of numerous
endocrinologic and immunologic systems.

Understanding the basic mechanisms underlying

this phenomenon helps to formulate rational approaches
to treatment and interventions.

Septic Shock

Sepsis-induced Hypotension

Severe Sepsis

Sepsis

Infection
Bone, et al. 1992 Chest 101:1644-1655
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Crit Care Med 2008; 36(1):

Sepsis
Infection (documented/suspected) + systemic
manifestations
Severe sepsis
Sepsis + sepsis-induced organ dysfunction or
tissue hypoperfusion
Sepsis-induced hypotension
a systolic BP(SBP) <90 mmHg or MAP <70
mmHg or SBP >40 mmHg or <2 SD below
normal for age in the absence of other cause of
hypotension
Septic Shock
Sepsis-induced hypotension persisting despite
adequate fluid resuscitation
Bone, et al. 1992 Chest 101:1644-1655
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Crit Care Med 2008; 36(1):

I. General variables
Fever (38.3C)
Hypothermia (core temperature 36C)
Heart rate > 90/min or 2 SD above normal value for

age
Tachypnea
Altered mental status
Significant edema or positive fluid balance (20 mL/kg
over 24 hrs)
Hyperglycemia (plasma glucose 140 mg/dL or 7.7
mmol/L) in the absence of diabetes

Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Crit Care Med 2008; 36(1):
296-327

II. Inflammatory variables

Leukocytosis (WBC count >12,000/L)
Leukopenia (WBC count <4000/L)
Normal count with >10% immature
WBC
Plasma CRP >2 SD above normal value
Plasma PCT >2 SD above normal value

Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Crit Care Med 2008; 36(1):
296-327

A.
B.
C.
D.
E.
F.
G.
H.
I.
J.

Initial resuscitation
Diagnosis
Antibiotic therapy
Source control
Fluid therapy
Vasopressors Norepineprine drip
Inotropic therapy
Steroids
Recombinant human activated protein C
Blood product administration

Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Crit Care Med 2008; 36(1):
296-327

Confirm infection
Confirm the responsible

pathogensBlood Culture
Susceptibility profile deescalation of antibiotic
therapy
BC negative in 50%, BUT
very likely caused by
bacteria/ fungi
decisions must be made
by clinician judgment

Weinstein MP, Reller LP, Murphy JR, et al.Rev Infect Dis; 5:35
53

Depends on :
Presumed site of infection
Suspected or known pathogens
Grams stain results
Previously have been documented to colonize or

infect the patient

Local resistance patterns
Limited spectrum of antibiotics available
Patients immune status, underlying diseases
Allergies
Cost

iv antibiotics as early as possible, within the 1st

hour
Broadspectrum active against likely
bacterial/fungal, good penetration into presumed
source
Reassess antimicrobial regimens daily
Duration 7-10 days, longer if inadequate response,

foci of infection, imunodeficiencies

Stop antimicrobial th/ if cause to be non
infectious

Combination therapy should be considered in

Pseudomonas infections, neutropenic patients < 3Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Crit Care Med 2008; 36(1):
5 days, de-escalate
296-327

Offers a broader antimicrobial spectrum:

Pathogens are not yet identified when th/ is

initiated
Polymicrobial infections may occur
Additive or synergictic antibiotic effect:

May be associated with clinical response

May allow dosage of the toxic drug
May prevent the emergence of resistance +/-

superinfections

Bochud, PY. Glauser MP, Carlet J, Calandra T. Empirical antibiotic therapy for patients with severe sepsis and
septic shock. 2002

Valuable only:

in vitro
in patients with neutropenia or bacteremic
infection
In vitro: inconsistently demonstrated, not

clinically relevant

Bochud, PY. Glauser MP, Carlet J, Calandra T. Empirical antibiotic therapy for patients with severe sepsis and
septic shock. 2002

Avaibility of newer broad-spectrum AB

(carbapenem, 3rd-4th gen cephalosporins)

offer adequate empirical th/
High bactericidal activity
Less toxic than aminoglycosides-based
combination th/

Bochud, PY. Glauser MP, Carlet J, Calandra T. Empirical antibiotic therapy for patients with severe sepsis and
septic shock. 2002