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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.
J Emerg Med. 2013 May;44(5):e341-4
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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