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However, there are many variations in normal body temperature, and this needs to be considered when measuring fever. The values given are for an otherwise healthy, non-fasting adult, dressed comfortably, indoors, in a room that is kept at a normal room temperature, during the morning, but not shortly after arising from sleep.  Furthermore, for oral temperatures, the subject must not have eaten, drunk, or smoked anything in at least the previous fifteen minutes.
Body temperature normally fluctuates over the day, with the lowest levels at 4 a.m. and the highest at 6 p.m. Therefore, an oral temperature of 37.5°C (99.5°F) would strictly be a fever in the morning, but not in the afternoon. Normal body temperature may differ as much as 0.4°C (0.7°F) between individuals or from day to day.  In women, temperature differs at various points in the [[menstrual cycle]], and this can be used for [[fertility awareness|family planning]] (although it is only one of the variables of temperature). Temperature is increased after meals, and psychological factors (like the first day in the hospital) also influence body temperature.
There are different locations where temperature can be measured, and these differ in temperature variability. [[Tympanic membrane]] [[thermometer]]s measure radiant heat energy from the tympanic membrane (infrared). These may be very convenient, but may also show more variability.
Children develop higher temperatures with activities like playing, but this is not fever because their set-point is normal. Elderly patients may have a decreased ability to generate body heat during a fever, so even a low-grade fever can have serious underlying causes in [[geriatrics]].


==Mechanism==
==Mechanism==

Revision as of 14:50, 7 May 2013

Fever
An analogue medical thermometer showing the temperature of 38.7 °C

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; M.Umer Tariq [3]

Synonyms and keywords: Pyrexia; febrile response



Mechanism

Temperature is regulated in the hypothalamus, in response to PGE2. PGE2 release, in turn, comes from a trigger, a pyrogen. The hypothalamus generates a response back to the rest of the body, making it increase the temperature set-point.

Hyperthermia: Characterized on the left. Normal body temperature (thermoregulatory set-point) is shown in green, while the hyperthermic temperature is shown in red. As can be seen, hyperthermia can be conceptualized as an increase above the thermoregulatory set-point.
Hypothermia: Characterized in the center: Normal body temperature is shown in green, while the hypothermic temperature is shown in blue. As can be seen, hypothermia can be conceptualized as a decrease below the thermoregulatory set-point.
Fever: Characterized on the right: Normal body temperature is shown in green. It reads "New Normal" because the thermoregulatory set-point has risen. This has caused what was the normal body temperature (in blue) to be considered hypothermic.

Pyrogens

A pyrogen is a substance that induces fever. These can be either internal (endogenous) or external (exogenous). The bacterial substance lipopolysaccharide (LPS) is an example of an exogenous pyrogen.

Endogenous

The cytokines (such as interleukin 1) are a part of the innate immune system, produced by phagocytic cells, and cause the increase in the thermoregulatory set-point in the hypothalamus. Other examples of endogenous pyrogens are interleukin 6 (IL-6), and the tumor necrosis factor-alpha.

These cytokine factors are released into general circulation where they migrate to the circumventricular organs of the brain, where the blood-brain barrier is reduced. The cytokine factors bind with endothelial receptors on vessel walls, or interact with local microglial cells. When these cytokine factors bind, they activate the arachidonic acid pathway.

Exogenous

One model for the mechanism of fever caused by exogenous pyrogens includes LPS, which is a cell wall component of gram-negative bacteria. An immunological protein called lipopolysaccharide-binding protein (LBP) binds to LPS. The LBP–LPS complex then binds to the CD14 receptor of a nearby macrophage. This binding results in the synthesis and release of various endogenous cytokine factors, such as interleukin 1 (IL-1), interleukin 6 (IL-6), and the tumor necrosis factor-alpha. In other words, exogenous factors cause release of endogenous factors, which, in turn, activate the arachidonic acid pathway.

PGE2 release

PGE2 release comes from the arachidonic acid pathway. This pathway (as it relates to fever), is mediated by the enzymes phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), and prostaglandin E2 synthase. These enzymes ultimately mediate the synthesis and release of PGE2.

PGE2 is the ultimate mediator of the febrile response. The set-point temperature of the body will remain elevated until PGE2 is no longer present. PGE2 acts on neurons in the preoptic area (POA) through the EP3 subtype of PGE receptors and the EP3-expressing neurons in the POA innervate the dorsomedial hypothalamus (DMH), the rostral raphe pallidus nucleus in the medulla oblongata (rRPa) and the paraventricular nucleus of the hypothalamus (PVN). Fever signals sent to the DMH and rRPa lead to stimulation of the sympathetic output system, which evokes non-shivering thermogenesis to produce body heat and skin vasoconstriction to decrease heat loss from the body surface. It is presumed that the innervation from the POA to the PVN mediates the neuroendocrine effects of fever through the pathway involving pituitary gland and various endocrine organs.

Hypothalamus response

The brain ultimately orchestrates heat effector mechanisms. These may be;

The autonomic nervous system may also activate brown adipose tissue to produce heat (non-exercise-associated thermogenesis, also known as non-shivering thermogenesis), but this seems mostly important for babies. Increased heart rate and vasoconstriction contribute to increased blood pressure in fever.

Types

Pyrexia (fever) can be classed as:

  • Low grade: 38–39°C (100.4–102.2°F)
  • Moderate: 39–40°C (102.2–104.0°F)
  • High-grade: 40–42°C (104.0–107.6°F)
  • Hyperpyrexia: over 42°C (107.6°F)

The last is clearly a medical emergency because it approaches the upper limit compatible with human life.

Most of the time, fever types can not be used to find the underlying cause. However, there are specific fever patterns that may occasionally hint the diagnosis:

  • Pel-Ebstein fever: A specific kind of fever associated with Hodgkin's lymphoma, being high for one week and low for the next week and so on. However, there is some debate as to whether this pattern truly exists.[1]
  • Continuous fever: Temperature remains above normal throughout the day and does not fluctuate more than 1°C in 24 hours, e.g. lobar pneumonia, typhoid, urinary tract infection, brucellosis, or typhus. Typhoid fever may show a specific fever pattern, with a slow stepwise increase and a high plateau.
  • Intermittent fever: Temperature is present only for some hours of the day and becomes normal for remaining hours, e.g. malaria, kala-azar, pyaemia, or septicemia. In malaria, there may be a fever with a periodicity of 24 hours (quotidian), 48 hours (tertian fever), or 72 hours (quartan fever, indicating Plasmodium vivax). These patterns may be less clear in travelers.
  • Remittent fever: Temperature remains above normal throughout the day and fluctuates more than 1°C in 24 hours, e.g. infective endocarditis.

Febricula[2] is a mild fever of short duration, of indefinite origin, and without any distinctive pathology.

Common Causes

Fever is a common symptom of many medical conditions:

Persistent fever which cannot be explained after repeated routine clinical inquiries, is called fever of unknown origin.

Complete Differential Diagnosis of the Causes of Fever

In Alphabetical Order. [3] [4]


Complete Differential Diagnosis of the Causes of Fever

(By Organ System)

Cardiovascular

Vasculitis, Infective Endocarditis, Dressler's syndrome, Cholesterol Emboli Syndrome,


Chemical / poisoning

2,4-Dinitrophenol, Abrin, Cadmium poisoning, Colchicine, Lithraea molleoides,



Dermatologic

Weber-Christian disease, Toxic epidermal necrolysis, Scrofula, Necrotizing fasciitis, Furunculosis, Cellulitis, Carbuncle,

Drug Side Effect

Abacavir , Abatacept , Acetazolamide , Acetohexamide , Acyclovir , Adalimumab , Albuterol , Aldesleukin , Alefacept , Alemtuzumab, Alendronate , Alfuzosin , Alglucerase , Allopurinol, Altretamine , Aminopterin, Amitriptyline , Amobarbital, Amphotericin B, Anagrelide , Anakinra , Anastrozole , Ancrod, Anisindione , Aripiprazole , Asparaginase , Atazanavir , Atorvastatin , Atovaquone , Atropine Ophthalmic , Auranofin , Benazepril , Benztropine Mesylate , Bepridil , Bevacizumab , Bisphosphonate, Bleomycin, Bortezomib , Brinzolamide Ophthalmic , Bumetanide , Busulfan , Butabarbital , Butoconazole Vaginal Cream , Calcitriol , Candesartan , Capecitabine , Captopril , Carboplatin , Carisoprodol , Carmustine , Carteolol , Caspofungin, Cefaclor, Cephalosporin, Cetuximab , Chlorambucil , Chlordiazepoxide , Chlorothiazide , Chlorthalidone , Ciclosporin, Cidofovir , Cladribine , Clofarabine, Clonazepam , Clorazepate , Clotrimazole , Cocaine, Colchicine, Colistimethate , Co-trimoxazole , Cyanocobalamin , Cyclobenzaprine , Cytarabine , Dacarbazine , Dactinomycin , Dalteparin Sodium , Dapsone, Daptomycin, Darbepoetin alfa, Darunavir , Daunorubicin , Deferasirox , Delavirdine , Desipramine , Dextroamphetamine and Amphetamine , Dextromethorphan, Diazepam , Diclofenac, Diethylpropion , Diflunisal , Diltiazem , Disopyramide , Dobutamine , Dolasetron , Donepezil , Doxorubicin , Efalizumab , Efavirenz , Emtricitabine , Enalapril , Enfuvirtide, Enoxaparin , Entacapone , Epinastine Ophthalmic , Epoetin Alfa , Erlotinib , Estazolam , Estradiol Topical , Etanercept , Ethosuximide , Etidronate , Etodolac , Etoposide, Ezetimibe , Famciclovir, Fenoprofen , Fipexide, Filgrastim , Flavoxate , Floxuridine , Flucytosine, Fludarabine Phosphate , Fluorouracil , Fluphenazine , Fluticasone and Salmeterol Inhalation , Fluvastatin , Fluvoxamine, Fosamprenavir , Foscarnet Sodium , Fosinopril , Furosemide , Gabapentin , Gatifloxacin , Gefitinib , Gemcitabine Hydrochloride , Glatiramer acetate, Glipizide , Glyburide , Goserelin , Granisetron , Grifulvin V, Guanethidine , Haloperidol, Heparin , Histrelin , Hydralazine , Hydrochlorothiazide , Ibandronate , Idarubicin , Ifosfamide , Imatinib , Imiglucerase , Imiquimod , Immune Globulin Intravenous , Indomethacin , Ipratropium and Albuterol Inhalation , Isocarboxazid , Itraconazole , Lamivudine , Levalbuterol Inhalation , Levetiracetam , Levomepromazine, Linezolid, Liothyronine , Lisinopril , Lorazepam , Lovastatin , Loxapine , Mechlorethamine , Meclofenamate , Mefenamic acid, Melphalan , Meprobamate , Mercaptopurine, Methadone withdrawl, Methimazole , Methocarbamol , Methsuximide , Methyclothiazide , Methyldopa and Hydrochlorothiazide , Methylphenidate, Metolazone , Metoprolol, Metronidazole, Miconazole , Mifepristone, Minocycline, Mitomycin , Modafinil , Moexipril , Moricizine , Moxifloxacin ophthalmic , Nabumetone , Nafcillin Sodium , Nalmefene, Natalizumab , Nefazodone , Nilutamide , Nitrofurantoin , Nortriptyline , Olanzapine , Ondansetron , Oprelvekin, Oseltamivir , Oxacillin Sodium , Oxaliplatin , Oxamniquine, Oxazepam , Oxcarbazepine , Paclitaxel, Palifermin , Paliperidone , Pamidronate , Pegaspargase , Pemetrexed , Pentetic acid, Pentostatin , Perindopril , Phenazopyridine , Phenobarbital , Phenytoin , Pimecrolimus topical , Pimozide , Pindolol , Piroxicam , Plicamycin , Posaconazole , Pravastatin , Prazepam , Praziquantel, Prazosin and polythiazide , Pregabalin , Primaquine , Primidone , Procainamide, Procarbazine , Prochlorperazine , Procyclidine , Propafenone , Propiomazine, Propylthiouracil , Protriptyline , Pyrazinamide, Quetiapine , Quinapril , Ramipril , Ranitidine bismuth citrate , Rasagiline , Ribavirin , Rifampicin, Riluzole , Risedronate , Risperidone , Rituximab , Rosuvastatin , Salsalate , Saquinavir , Sargramostim , Scopolamine, Secobarbital , Sibutramine, Silver sulfadiazine , Simvastatin , Sirolimus , Sodium oxybate , Solanine, Spironolactone , Stool softeners , Streptozocin , Strontium-89 chloride , Sulfadiazine , Sulfasalazine , Sulfinpyrazone , Sulfisoxazole , Sulindac , Sunitinib , Tamoxifen , Tamsulosin , Tanapox, Temazepam , Temozolomide , Teniposide , Terbinafine , Teriparatide (rDNA origin) , Testosterone Transdermal , Thiabendazole, Thioamide, Thioguanine , Thiotepa , Thyroid Medication , Ticarcillin Disodium , Ticlopidine , Tiludronate , Tiotropium Inhalation , Tipranavir , Tirofiban, Tocainide , Tolazamide , Tolbutamide , Topotecan Hydrochloride , Trandolapril , Tranylcypromine , Trastuzumab , Trazodone , Triamterene, Triazolam , Trichothecene, Trihexyphenidyl , Trimethadione , Trimetrexate Glucuronate , Trimipramine , Troleandomycin , Valacyclovir , Valproate semisodium, Valproic Acid , Verapamil , Vinblastine , Vinorelbine Tartrate , Voriconazole, Vorinostat , Zalcitabine , Ziprasidone , Zoledronate, Zonisamide ,


Ear Nose Throat

Sinusitis, Pharyngoconjunctival fever, Pharyngitis, Peritonsillar abscess, Otitis media, Orbital cellulitis, Mastoiditis, Ludwig's angina, Laryngitis, Gradenigo's syndrome, Dacryocystitis, Croup, Bezold's abscess,

Endocrine

Subacute thyroiditis, Exopthalmos, Diabetes insipidus, De Quervain's thyroiditis, Adrenal hemorrhage,

Environmental

Zinc oxide, Silicosis, Polytetrafluoroethylene, Metal fume fever,

Gastroenterologic

Ulcerative colitis, Toxic megacolon, Pseudomembranous colitis/C.difficile, Peritonitis, Perianal abscess, Pancreatitis, Ischemic colitis, Intra-abdominal abscess, Ileitis, Hepato-biliary diseases, Gastritis, Gastroenteritis, Gastrointestinal perforation, Diverticulitis, Crohn's disease, Colitis, Cholangitis, Cholecystitis, Caroli's Disease, Caecitis, Appendicitis, Anal abscess,

Genetic

Muckle-Wells syndrome, Sickle-cell disease, Krabbe disease, Hyperimmunoglobulinemia D with recurrent fever, Fabry's Disease, Cystic Fibrosis, Familial Mediterranian Fever, Blue diaper syndrome,

Hematologic

Disseminated Intravascular Coagulation, Blood Transfusion, Acute lymphoblastic leukemia, Acute myeloid leukemia,

Iatrogenic

Transfusion reaction, Transfusion-associated graft versus host disease, Serotonin syndrome, Malignant hyperthermia, Adjustable gastric band,

Infectious Disease

Adenoviridae, African Hemmorhagic Fever, African horse sickness, African swine fever virus, African Trypanosomiasis, Alkhurma virus, Allergic bronchopulmonary aspergillosis, Alphavirus, Anthrax, Aphthovirus, Arbovirus, Arenavirus, Aripiprazole , Arterivirus, Aspergillosis, Astroviridae, Babanki virus, Bacillary angiomatosis, Bartonellosis, BK virus, Blackwater fever, Blastomycosis, Bordetella pertussis, Bornholm disease, Borrelia, Boutonneuse fever, Brucellosis, Bubonic plague, Buruli ulcer, Bwamba Fever, Cabin fever, Campylobacter jejuni, Cat scratch fever, Chagas disease, Chickenpox, Chlamydia, Chlamydophila pneumoniae, Clostridium Difficile, CMV , Coccidioidomycosis, Colorado tick fever virus, Cotton fever, Coxiella burnetii infection, Coxsackie A virus, Crimean Congo Hemorrhagic Fever, Cryptosporidiosis, Cyclosporiasis, Dengue Fever, Dientamoebiasis, Diphtheria, Ebola haemorrhagic fever, Echovirus, Enterotoxigenic Escherichia coli, Epstein-Barr virus, Fasciolosis, Fasciolopsiasis, Filoviridae, Flavivirus, Fusarium, Giardiasis, Gonorrhea, Group A streptococcal infection, Haemophilus influenzae, Haverhill fever, Hantavirus Pulmonary Syndrome, Herpangina, Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis E, Herpes zoster, Herpesviridae, HIV/AIDS, Hookworm, Infectious mononucleosis, Influenza virus , Lassa Fever, Legionellosis, Leishmaniasis, Leptospirosis, Lemierre's Syndrome, Listeriosis, Lyme disease, Malaria, Measles, Melioidosis, Miliary tuberculosis, Mumps, Murray Valley encephalitis virus, Mycobacterium avium complex, Mycoplasma pneumoniae, Naegleria infection, Nocardiosis, Noma (disease), Norovirus infection, Omsk hemorrhagic fever, O'nyong'nyong virus, Opisthorchis infection, Oropouche virus, Paracoccidioidomycosis, Paragonimus Infection, Paratyphoid fever, Penicilliosis, Pityriasis rosea, Pneumocystis jirovecii pneumonia, Poliomyelitis, Pontiac fever, Psittacosis, Q fever, Rat-bite fever, Rhinovirus, Rheumatic fever, Rickettsial infections, Rift Valley fever virus, Rocky Mountain Spotted Fever, Roseola, Ross River Fever, Rotavirus, Rubella, Salmonella enteritidis, Salmonella typhi infection/ Typhoid fever, Scarlet fever, Schistosomiasis, Septic arthritis, Shigellosis, Severe acute respiratory syndrome, Sindbis virus, Sleeping sickness, Smallpox, Marburg hemorrhagic fever, Mediterranean spotted fever, Staphylococcal enteritis, Streptococcus pyogenes, Swine flu, Syphillis, TORCH infections, Toxic Shock Syndrome, Toxocara infection, Traveler's diarrhea, Trench Fever, Trichinosis, Tularemia, Varicella-zoster virus, Vibrio parahaemolyticus, Vibrio vulnificus, Visceral leishmaniasis, West Nile Virus, Whipple's disease, Yellow Fever Virus, Yersinia enterocolitica Infection (Yersiniosis), Yersinia Pestis Infection, Yersinia pseudotuberculosis, Zika fever,


Musculoskeletal / Ortho

Septic arthritis, Reactive Polyarticular Arthritis,


Neurologic

Subdural hygroma, Neuroleptic malignant syndrome, Meningitis, La Crosse encephalitis, Krabbe disease, Craniopharyngioma, Brain Abscess, Acute Disseminated Encephalomyelitis,

Nutritional / Metabolic

Blue diaper syndrome, Gout, Porphyria

Obstetric/Gynecologic

Pelvic inflammatory disease, Childbirth,

Oncologic

Acute lymphoblastic leukemia, Acute myeloid leukemia, Pel-Ebstein fever, Synovial sarcoma, Renal Cell Carcinoma, Myxoma, Mesothelioma, Lung cancer, Juvenile Myelomonocytic Leukemia (JMML), Kaposi's sarcoma, Hodgkin's lymphoma, Craniopharyngioma, Chronic myelogenous leukemia,


Opthalmologic

Tolosa-Hunt syndrome, Temporal arteritis, Cogan syndrome, Acute posterior multifocal placoid pigment epitheliopathy,

Overdose / Toxicity

Vitamin A, Coley's Toxins, Didanosine , Ethchlorvynol, Ganciclovir , Melarsoprol, Methotrexate , Mycophenolate , Nevirapine , Oxybutynin , Oxycodone and aspirin , Peginterferon alfa-2a , Phenelzine , Phentermine, Selegiline , Solifenacin , Valganciclovir ,

Psychiatric No underlying causes
Pulmonary

Tuberculosis, Tracheitis, Pulmonary alveolar proteinosis, Pleurisy, Lung cancer, Lung abscess, Empyema, Community-acquired pneumonia, Bronchitis, Atelectasis, Alveolitis, Allergic bronchopulmonary aspergillosis, Acute Chest Syndrome,

Renal / Electrolyte

Urinary tract infection, Pyelonephritis, Interstitial nephritis,

Rheum / Immune / Allergy

Wegener Granulomatosis, Varicella (Chickenpox) Vaccine , Yellow Fever Vaccine , Takayasu's Arteritis, Systemic lupus erythematosus, Still's disease, Serum sickness, Sarcoidosis, Rheumatoid arthritis, Rabies vaccine , Polyarteritis nodosa, Lupoid hepatitis, Langerhans cell histiocytosis, Kawasaki disease, Hay fever, Churg-Strauss Syndrome, Bacillus Calmette-Guerin (BCG) Vaccine ,


Sexual

Syphillis, Lymphogranuloma venereum,

Trauma No underlying causes
Urologic

Prostatitis,

Miscellaneous

Retinoic acid syndrome, POEMS syndrome, Omphalitis, Occult abscess, Neutropenia, Mastitis, Lymphocytopenia, Kikuchi disease, Immune reconstitution inflammatory syndrome, Herxheimer reaction, Heroin withdrawl, Hemophagocytic lymphohistiocytosis, Fetal alcohol syndrome, Fat Embolism Syndrome, Cytokine release syndrome, Congenital syphilis, Cocaine, Adiposis dolorosa,

Usefulness of Fever

There are arguments for and against the usefulness of fever, and the issue is controversial.[5][6] There are studies using warm-blooded vertebrates[7] and humans[8] in vivo, with some suggesting that they recover more rapidly from infections or critical illness due to fever.

Theoretically, fever has been conserved during evolution because of its advantage for host defense.[5] There are certainly some important immunological reactions that are sped up by temperature, and some pathogens with strict temperature preferences could be hindered.[9] The overall conclusion seems to be that both aggressive treatment of fever[8] and too little fever control[5] can be detrimental. This depends on the clinical situation, so careful assessment is needed.

Fevers may be useful to some extent since they allow the body to reach high temperatures. This causes an unbearable environment for some pathogens. White blood cells also rapidly proliferate due to the suitable environment and can also help fight off the harmful pathogens and microbes that invaded the body.

Treatment

Fever should not necessarily be treated. Fever is an important signal that there's something wrong in the body, and it can be used for follow-up. Moreover, not all fevers are of infectious origin.

Even when treatment is not indicated, however, febrile patients are generally advised to keep themselves adequately hydrated, as the dehydration produced by a mild fever can be more dangerous than the fever itself. Water is generally used for this purpose, but there is always a small risk of hyponatremia if the patient drinks too much water. For this reason, some patients drink sports drinks or products designed specifically for this purpose.

Most people take medication against fever because the symptoms cause discomfort. Fever increases heart rate and metabolism, thus potentially putting an additional strain on elderly patients, patients with heart disease, etc. This may even cause delirium. Therefore, potential benefits must be weighed against risks in these patients. In any case, fever must be brought under control in instances when fever escalates to hyperpyrexia and tissue damage is imminent.

Treatment of fever should be based primarily on lowering the set-point, but facilitating heat loss may also contribute. The former is accomplished with antipyretics. Wet cloth or pads are also used for treatment, and applied to the forehead. Heat loss may be an effect of (possibly a combination of) heat conduction, convection, radiation, or evaporation (sweating, perspiration). This may be particularly important in babies, where drugs should be avoided. However, if water that is too cold is used, it induces vasoconstriction and prevents adequate heat loss.

References

Articles

  1. http://content.nejm.org/cgi/content/short/333/1/66
  2. Febricula, definition from Biology-Online.org, consulted June 7, 2006 http://www.biology-online.org/dictionary/Febricula
  3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:77 ISBN 1591032016
  4. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:68 ISBN 140510368X
  5. 5.0 5.1 5.2 Schaffner A. Fever—useful or noxious symptom that should be treated? Ther Umsch 2006; 63: 185-8. PMID 16613288
  6. Soszynski D. The pathogenesis and the adaptive value of fever. Postepy Hig Med Dosw 2003; 57: 531-54. PMID 14737969
  7. Su, F.; Nguyen, N.D.; Wang, Z.; Cai, Y.; Rogiers, P.; Vincent, J.L. Fever control in septic shock: beneficial or harmful? Shock 2005; 23: 516-20. PMID 15897803
  8. 8.0 8.1 Schulman, C.I.; Namias, N.; Doherty, J., et al. The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study. Surg Infect (Larchmt) 2005; 6:369-75. PMID 16433601
  9. Fischler, M.P.; Reinhart, W.H. Fever: friend or enemy? Schweiz Med Wochenschr 1997; 127: 864-70. PMID 9289813

Books

  • Rhoades, R. and Pflanzer, R. Human physiology, third edition, chapter 27 Regulation of body temperature, p. 820 Clinical focus: pathogenesis of fever. ISBN 0-03-005159-2
  • Kasper, D.L.; Braunwald, E.; Fauci, A.S.; Hauser, S.L.; Longo, D.L.; Jameson, J.L. Harrison's Principles of Internal Medicine. New York: McGraw-Hill, 2005. ISBN 0-07-139140-1.

External Links

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