Definition of pyrexia, hyperpyrexia hyperthermia

Pathophysiology of fever Evaluate best methods to measure

temperature Diagnostic and therapeutic approach for fever

in select patient populations Review of IDSA guidelines for important select

clinical conditions that cause fevers

Normal temperature 36.5ºC - 37.5ºC› Lowest temperature at 6 AM› Highest at 4 - 6 PM› Diurnals variations are maintained during illness

Hypothalamus control› Heat producers: muscle and liver› Heat dissipators: skin and lungs

Fever› A.M. temperature > 37.2 C› P.M. temperature > 37.7 C

Hyperpyrexia › Temp > 40.0ºC -41.5ºC

Each 1○C increase = 13% increase O2 consumption (without shivering)

Journal of Infection and Public Health (2011) 4, 108—124

Hyperpyrexia› Temp > 40.0ºC -41.5ºC

Severe infections CNS hemorrhage

Hyperthermia (Heat stroke)› Does not involve intrinsic body pyrogens› Exertional vs non-exertional› Skin: "hot and dry"

Drug induced hyperthermia Malignant hyperthermia Neuroleptic malignant syndrome Serotonin syndrome

Where to measure

Women and ovulation› Lower temp 2 weeks

before ovulation› Raises by 0.6 during

Higher temperatures after eating

Oral N/A

Rectal +0.5 ºC

TM +0.5 ºC

Axillary -0.5 ºC

Antipyretics

Exogenous Pyrogens

Steroids

Related to phases of fever Initiation phase

› Elevation of set point chills/shivering/rigors

Plateau phase› Tc = Set point

Defervescence› Tc > set point

› Patient feels warm sweating

Tc = Core Temp

Non-infectious causes of fevers› Connective tissue disease› Malignancy› Medications› Myocardial infarction› Pulmonary embolism

Fever curve/height does not correlate with etiology› Fever > 39.4 F = Greater concern infection› Fever > 40.8 = Tissue damage

Fever within 48 hours of admission is often caused by organisms found in the community

Therapies may interfere with the generation of fevers› NSAIDS, steroids, etc.

Continuous fever› Drugs, RMSF, gram negative pneumonia

Remittent fever› Malaria, Legionella

Intermittent fevers› Endocarditis, peritonitis, sepsis, TSS

Do not use fever patterns alone to make a diagnosis

Likelihood that fever is due to bacterial infection:› Advanced age› Indwelling catheter› Nursing home residency› Leukocytosis› Elevated ESR› Diabetes

Identification of source complicated if difficult history and physical examination› Understand potential causes of fever› Studied approach

EPIDEMIOLOGY

Recent RemoteSocial Risks

Host Factors

AgeSexLocal DefensesPhagocytesComplementAntibodiesCellular Immunity

Clinical Manifestation

sPhysical Exam

Blood cultures › Mandatory if new fever*

› Clinical findings cannot exclude bacteremia› 2 sets from two different sites› 30-60 mins apart› Peripheral always preferred

› Contamination vs bacteremia› Volume matters

› 3% ↑ Sensitivity per mL› Contamination:

› Staph epidermidis, Staph hominis, Bacillus spp, Corynecbacterium

› Gram negative, fungi, and anaerobes are always pathogenic

› Document clearance of bacteremia!

Sputum – Gram stain and culture› Sputum vs saliva› New sputum, change in color, amount, thickness, new

or progressive pulmonary infiltrate, increased RR, increased in VE, decreased oxygenation.

Urine culture › Catheter, obstruction, renal calculi, GU surgery, trauma,

neutropenia Stool culture Nasal culture Throat culture Spinal fluid culture Wound abscess culture GU culture

55-year-old man with a history of mitral regurgitation seeks care after an episode of transient weakness in his right arm and speech difficulties. He underwent dental scaling 1 month earlier. He notes recent intermittent fevers and weight loss. On cardiac examination, his regurgitation murmur appears to be unchanged. A TTE shows a mobile, 12-mm mitral-valve vegetation and grade 2 (mild) regurgitation. Magnetic resonance imaging of the brain reveals recent ischemic lesions. How should the patient be further evaluated and treated?

N Engl J Med. 2013 Jun 27;368(26):2536.

N Engl J Med 2013; 368:1425-1433

3 sets (aerobic & anaerobic bottles) from different sites› One hour apart

Repeat blood cultures every 24 hours CBC, ESR, RFP, U/A, Urine culture ECG Imaging

Circulation 2005;111;e394-e434

Native valve acute bacterial endocarditis› Vancomycin +/- gentamycin

Prosthetic valve endocarditis› Vancomycin + cefepime + gentamycin› **Staphylococcal prosthetic-valve infective

endocarditis, the regimen should include rifampin whenever the strain is susceptible + gentamicin

Repeat blood cultures until defervescence and blood culture negative› Fever may last a week

Duration of abx : 4-6 weeks

Heart failure Uncontrolled infection

› Abscess, aneurysm, dehiscence Persistent fevers or positive blood

cultures for 5-7 days Prevention of embolism from large

vegetations (10-15 mm)

57-year-old man presents with fever, chills, and new lumbar back pain 2 weeks after undergoing a prostate biopsy because of an increased PSA level. His temperature is 39.7°C; he has an enlarged, tender prostate and lumbar spine tenderness. His white-cell count is 9.1, and the CRP level is 3.43 mg/L.

Urine and blood cultures reveal multidrug-resistant, extended-spectrum β-lactamase–producing Escherichia coli susceptible to imipenem. How should he be evaluated and treated? N Engl J Med 2010;362:1022-9.

N Engl J Med 2010;362:1022-9.

ESR, CRP >95% sensitivity Blood cultures are crucial (30 - 78%) MRI : high signal on T2 weighted image

› CT or MRI are not 100% specific Biopsy: If blood cultures are negative or

if polymicrobial is suspected› Open or CT guided› Biopsy prior to antibiotics is preferred

Drain periosteal abscess

58 year old man is hospitalized because of fever and chills for the last 2 days. He denies productive cough, shortness of breath, headaches, nausea, vomiting, abdominal pain, diarrhea, dysuria, or rash. According to his wife, he has been "acting differently" for the past 24 hours. He was recently diagnosed with AML. His leukemia is currently in remission, and he is receiving maintenance chemotherapy.

He has no known drug allergies. Works at a local grocery and denies use of tobacco, alcohol or illicit drug. His temperature is 39.4 ºC, blood pressure 81/45 mm Hg, pulse is 122/min, and respirations 22/min. SaO2 96% on RA.

A Hickman catheter is present in the left IJ and it shows erythema and induration over the insertion site. Two sets of blood cultures are obtained, one from a peripheral vein and second from the catheter port. 3 liters of normal saline are given IV, this improves patient's hemodynamics. CXR shows infiltrates. UA without evidence of infection.

Risk factors: Catheters, skin breakdown, GI mucositis, immune defects associated with malignancy

Seeding of bloodstream by GI flora* Evaluation: Physical Exam

› Teeth, eyes, skin, lungs, abdomen, rectum› Catheter sites› Avoid digital rectal examination

Work up : CBC with diff, RFP, CXR, LFTs, UA, at least two sets of blood cultures, CXR, ?C. difficile

Low threshold for ordering a CT scan Other:

› LP if confused, fungal markers*, bronchoscopy

Type of underlying malignancy› Abnormal antibody production

High risk for encapsulated organism infection

› T cell defects (e.g., Hodgkins Lymphoma) High risk of Intracellular infections

Breeches in host defenses related to the underlying malignancy

The direct effects of chemotherapy on mucosal barriers and the immune system

Bacteria are the most frequent infectious causes of neutropenic fever

Shift from gram-negative bacteria to gram-positive bacteria

Gram-negative bacteria (eg, P. aeruginosa) are generally associated with the most serious infections

S. epidermidis is the most common gram-positive pathogen

An infectious source identified in 20 to 30 %

Ann Intensive Care. 2011;1:22-22.

Vancomycin or Linezolid* Fever not resolved after 3-5 days Hemodynamically instability / Sepsis CXR with pneumonia Blood culture with gram positive bacteria Suspicion for serious catheter-related

infection › Chills/rigors with infusion through catheter› Cellulitis around catheter

Severe mucositis if fluroquinolone as prophylaxis and ceftazidime as empiric therapy

MRSA colonization Remember Leuconostoc, Lactobacilus, and

Pediococcus not covered with vancomycin

Fungal colonizers› Candida yeast and aspergillus

Antifungal therapy after day 5-7› Caspofungin *› Amphoterecin B› Voriconozale› Micafungin

Do not use fluconazole in this setting Fungal coverage resolves fever in 50% of patients Cryptococus, Fusarium, Mucor, histo, blasto, cocci ?Duration

› 14 days if source if known› Source not known: Until afebrile + ANC > 500 c/µL

Role of G-CSF, $$ Anaerobic infections are not commonly seen

Tumor and Malignancy

Lymphoma, especially non-Hodgkin's* Leukemia Renal cell carcinoma (20% of cases) Hepatocellular carcinoma or other

tumors metastatic to the liver Atrial myxomas (30% of cases)

"“There are no shortcuts to any place worth going.” 

Beverly Sills

20-year-old man who had a history of IV drug use and multiple sexual partners initially presented to the ED with a chief complaint of blood per rectum when he passed stool, and chills for the prior few days. His work-up was normal, including a rapid HIV screen, and he was discharged.

He returned 2 weeks later with constipation, fatigue, myalgias, decreased urination, chills, and a productive cough. His physical examination was most remarkable for temp 39.2, HIV antibody test was negative, but his laboratory tests showed an elevation of CK, amylase, and lipase. His blood count showed a normal hematocrit and white blood cell count. HIV viral load was reported as > 1,000,000 copies/mL.

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Fever almost always accompanies the acute retroviral syndrome

Drug adverse effect (Bactrim) Lymphoma Opportunistic disease

Opportunistic infections uncommon if CD4 > 200› TB exception› M. avium rare if CD4 > 50

Neutropenia can develop in patients with HIV› Primary infection› Secondary infection› Bone marrow suppression of therapy

Zidovudine HIV + Neutropenia + Fever = Infection*

Bacteria:› More common in children > adults, Strep.

Pneumonia, salmonella, enteric bacteria, pseudomonas, salmonella, enteric bacteria

Viruses› HSV, CMV, VZV, EPV, Adenovirus,

parainfluenza, measles Fungi

› Candida, cryptococcus, histoplasma, coccidioides, pneumocystis carinii, toxoplasma, cryptosporidia, microsporida

N Engl J Med. 1999 Sep 16;341(12):893-900

Fever > 40.8 Immunosuppresion

› Neutropenia› Asplenia› Hypogammaglobulinemia› Cirrhosis

Elderly Unstable vitals signs Presence of prosthetic device/foreign body Recent bite, travel

Fever coinciding with administration Disappearing after the discontinuation› Diagnosis of exclusion› 6.7% of patients admitted› Timing not always helpful: Median 8 days

HIV infection increased susceptibility to drug reactions, including fever

↑ Serum/Urine eosinophil (<20% of patients) Causes: Pyrogenic contaminants,

hypersensitivity reactions, genetic determinants

Stop most probable offending drug first

Fever and Connective Tissue Diseases

Vasculitis Giant cell arteritis Adult still’s disease Polyarteritis nodosa Granulomatosis polyangitis Mixed cryoglobulinemia SLE Sarcoidosis

Yes› Temperature > 40.8 ºC (Tissue damage)› Metabolic stress of fever (e.g., ACS)

No› Stimulates immune function› Decreases iron necessary for pathogen

survival› Artificially lowering temperature does not

allow for monitoring

“The future belongs to those who believe in the beauty of their dreams.” 

–Eleanor Roosevelt

47 year old man with HTN, HLP, asthma, admitted to the MICU 5 days ago from ED with acute asthma attack which required intubation in the ED. Initial vitals Temp: 38.7, HR 110, BP 90/42, 95% on the vent with 50% FiO2, RR 20 (above vent). Patient has right radial arterial line, right IJ central line, sites which do not appear erythematous or indurated. Pt also has OG. Chest x-ray with new small left lower lobe infiltrate, ETT 3 cm above carina, Right central line with tip in SVC, no pneumothorax. Labs with CBC 15/12/36/253, 79% neutrophils, 2% eosinophils. RFP within normal limits. Patient is on steroids, but no antibiotics.

How would you work up and manage fever in this patient?

50% of patients admitted to the ICU Fever associated with mortality in ICU Classifications

› Hyperthermia syndromes Heat stroke, malignant hyperthermia

› Infectious Bacterial, protozoa, fungal, viral, parasitic

› Non-infectious Transfusion reactions, drugs, VTE,

hematomas, MI, pancreatitis, neurogenic fever

J Intensive Care Med. 2012 Sep-Oct;27(5):290-7.

Compromised natural host defenses› Invasive monitoring

Violation of skin barrier Microbial colonization

› Endotracheal intubation Retards mucociliary clearance

› Nasogastric tubes Splints open GE junction aspiration of gastric

contents› TPN› Already on antibiotics resistant infections

Non-infectious causes More so if temp > 41 Without Shock› Transfusion reactions› Drug fever› Acalculous cholecystitis› Mesenteric ischemia› Pancreatitis› Thromboembolic disease Without Shock› Adrenal crisis› Thyroid storm› Acute hemolytic transfusion reaction

Empiric antibiotics› Deteriorating› Shock› Neutropenic› LVAD› Fever > 38.9 C(102 F)

Removal of lines

Definition:› Temp: > 38.3ºC› Lasting >3 weeks › 1 week of intensive studying*

History, PE, CBC with diff, LFTs, blood cultures (3 sets from different sites without abx), hepatitis serology, UA, CXR

Same major categories:› Infectious, malignancies, connective tissue

dz

True FUO are uncommon Typical distribution:

› Non-infectious 22%› Infection 16%› Malignancy 7%› Miscellaneous 4%› No diagnosis 51%

Contributing factors: Age, AIDS, Neutropenia

No diagnosis in 10-50% of cases› Good prognosis, mortality ~1%

ESR or CRP Serum lactate dehydrogenase Tuberculin skin test or interferon-gamma release assay HIV antibody assay and HIV viral load for patients at

high risk Three routine blood cultures drawn from different sites

over a period of at least several hours without Administering antibiotics, if not already performed* Rheumatoid factor Creatine phosphokinase Heterophile antibody test in children and young adults Antinuclear antibodies Serum protein electrophoresis CT scan of chest, abdomen, pelvis

Controversial and nonspecific Highly sensitive: Gallium-67 and indium-111

Leukocyte scan Compared to CT / US covers a larger body area

In series of 145 cases of FUO:› Useful in 29% of cases› Fall positives 11-20% of cases

Reserve nuclear evaluation if initial eval remains negative and a screening “look” at whole body is desired

Be aware of false and true positive rates

Temperature should be measured with precision and consistency

Approach to patient with fever requires evaluation of clinical manifestation, host factors and epidemiology

Neutropenic fever is a medical emergency In all cancer patients presenting with

neutropenic fever, empiric antibacterial therapy should be initiated immediately

Have a low threshold for antibiotics in the critically ill patient

Love fever Barrel fever Buck fever Staff fever Cabin fever Disco fever (boogie fever) Gate fever Bieber fever

Muriel Ghosn, MD Salim Thabet, MD

"I do not actually remember which one of my parents taught me this, but one of them told me: 'Son, in this world there are stupid people and there are smart people; there are mean people and there are nice people. If you are smart and nice, you will do well in your work and have a lot of friends. If you are smart and mean, you will be successful but not happy. If you are stupid and nice, you will not be successful but at least you will be happy. But if you are stupid and mean, you will not get anywhere in life.' knowing my limitations, I have always aspired to be the nicest person I can ever be."

--Chin-to Fong , MDUniversity of Rochester

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