Fever ALINA IOVLEVA, PGY-3. Learning objectives: 1.Definition 2.Pathophysiology of temperature regulation 3. Difference between fever and hyperthermia.

FeverAlina Iovleva, PGY-3

Learning objectives: 1.Definition

2.Pathophysiology of temperature regulation

3. Difference between fever and hyperthermia

4. Infectious Causes of fever

5. Empiric antibiotics

6. Neutropenic Fever

7. FUO

CaseMs. K is a 65 year old woman with DLBCL on active chemotherapy who comes in with persistent low grade fevers to the low 38s and new DOE. She feels otherwise well.

T 38.1, HR 112, BP 134/76. CV exam is unremarkable and lungs are clear. Abdomen is soft, non-tender, non-distended. RLE have 1+ pitting edema to 1/3 of the way up the shin. Negative Homan sign.

CXR without infiltrate. CBC and CMP unremarkable. US + for DVTNot all fever is infectious in etiology.

Body Temp Regulation

Balance between heat production and dissipation

“Normal” body temperature -think range: 35.6oC-38.2oC, mean 36.8oC +/-0.4oC

Anatomic Variability:

-Rectal >oral by 0.4oC and > tympanic membrane by 0.8oC

-which one is right?

Physiologic variability:

-circadian rhythmicity

-age (impaired thermoregulation in elderly, blunted circadian rhythm amplitude)

-gender, activity, digestion, local inflammation, ovulation, meds, neuropsych

Fever T>38.3oC

“a state of elevated core temperature, which is often, but not necessarily, part of the defensive responses of multicellular organisms (host) to the invasion of live (microorganisms) or inanimate matter recognized as pathogenic or alien by the host.”

Benefits vs Risks of Fever Benefits:

- present in other species, evolutionary conserved

-?increases resistance to pathogens

-positive correlation between fever and survival in G- sepsis, SBP, Candidemia

-production of cytokines

Risks:

-discomfort

-increased metabolic demands

-elevated HR/tachypnea

When to treat fever?MI, Stroke. Fevers correlates with worse outcome

CV/Pulm disease

Temp above 41oC

fever induced mental dysfunction in elderly

Antipyretic agentsTylenolNSAIDSAspirin

What about cooling blanket?External cooling->shivering->increased heat production->feverVasospasm of coronaries

Case #2Mr. B is 65 y.o male, with depression, chronic pain, who presented with recurrent MRSA cellulitis

He is on Celexa and Bupropion for depression, and tramadol for pain. For MRSA cellulitis he was started on Linezolid. Day 2 of hospitalization, he felt a bit nauseous and was given IV Zofran.

6 hours later nurse calling you to report temperature of 41.5oC. BP 170/90, HR 110. She reports patient being agitated and confused.

Your exam significant for increased muscle tone and hyperreflexia

Dx: Serotonin Syndrome

Fever vs Hyperthermia -Fever is a normal, controlled response to an insult; <41oC -Hyperthermia is dysregulation of thermoregulation; >41.1oC◦ sustained elevation in core temperature◦ lacking the diurnal fluctuation typical of fever and normal body temperature

◦ does not respond to antipyretic therapy◦ Ex: heat stroke, serotonin syndrome, NMS, malignant hyperthermia

Antidepressants: SSRI/MAOi

Antiemetics: Zofran, Reglan

Abx: Linezolid, Ritonavir

Analgesics: fentanyl, tramadol

Tx: supportive, cyproheptadine, benzos

Tx of hyperthermia: paralysis

Serotonin Syndrome

Neuroleptic Malignant Syndrome

->neuroleptic medications (dopamine antagonists)

->withdrawal of L-Dopa in Parkinson’s

->Sx: ◦ slow onset◦ Bradykinesia/akinesia◦ Lead pipe rigidity◦ Hyperthermia◦ Autonomic instability

->Tx◦ Dantrolene, Bromocriptine, Amantadine

Edward W. N Engl J Med 2005; 352:1112-1120March 17, 2005

Infectious Causes of FeverHost

Syndrome

Bugs

Drugs

Fever in “Immunocompetent” hostCommunity acquired

Healthcare associated◦ Hospitalization for 2+ days w/ in past 90 days◦ HD w/ in 30 days◦ NH or LTAC w/ in 30 days◦ IV therapy (chemo, Abx) w/in 30 days◦ Wound care w/ in 30 days◦ Family member w/ MDR pathogen

Hospital acquired◦ >48 hrs since admission◦ HAP, VAP (>48hrs since intubation)◦ CAUTI◦ CLABSI◦ SSI

Geographic/Travel relatedo ex. Malaria, Lyme diseases, Valley Fever

Empiric Antibiotics overview

Vanc/Zosyn

Empiric antibiotics:

Sepsis :◦ Vanc/Zosyn or Vanc+Aztreonam+metronidazole (if anaerobic infection suspected)

Cellulitis w/ abscess:◦ Oral: Bactrim or Doxy◦ IV: Vancomycin

Cellulitis w/o abscess:◦ Oral: Keflex or Bactrim◦ IV: Vancomycin or Cefazolin

Necrotizing STI:◦ IV: Van/Zosyn or Vanc/Aztreonam/Metronidazole

Empiric antibiotics: Intra-abdominal infections/Biliary tree infections

◦ Oral: Augmentin or Cipro+metronidazole◦ IV: Zosyn or Aztreonam+metronidazole ◦ Add Vanc if high suspicion for MRSA/unstable patient

CAP:◦ Ceftriaxone/Azithro or Levofloxacin

Aspiration:◦ Augmentin or Moxifloxacin

HCAP: ◦ Vanc/Zosyn

Empiric antibiotics: Endocarditis

◦ Native valve: Vanc+Ceftriaxone+Gentamycin or Vanc+Gent◦ Prosthetic valve: Vanc+Gent+ Rifampin

Joint Infection◦ Ceftriaxone+Vanc or Aztreonam+Vanc◦ Post-surgical: Vanc/Zosyn or Vanc/Aztreonam

Diabetic Foot◦ Vanc/Zosyn or Vanc+Aztreonam+metronidazole

Empiric AntibioticsBacterial meningitis:o Ceftriaxone and Vanc or Meropenem +Vanco Add Amp if elderly

Complicated UTIo Not Cipro or Nitrofurantoin

C.DiffoMild: Metronidazoleo Severe: PO Vancoo Complicated: PO Vanc +IV metronidazole

Neutropenic Feversingle oral temperature of >38.3°C (101°F) or a temperature of >38.0°C (100.4°F) sustained for >1 hourNeutropenia: ANC <1500-mild; ANC < 500-severeLow vs High risk patients

Neutropenic FeverObtain blood cultures (peripheral and from any port), urine cultures, C.diff, imaging

EMPIRIC GRAM NEGATIVE coverage: carbapenems or antipseudomonal beta-lactam

GRAM POSITIVE coverage with vancomycin IF you suspect cellulitis, port/line infection, PNA, or if patient is clinically unstable

FUNGAL coverage if patient has not defervesced after 4-7 days of broad spectrum Abx.

Fever in HIV

What is latest CD4 and previous opportunistic infections?◦ ->normal: think common infections◦ ->low: think OI

On HAART or not? When was it started? ◦ ->IRIS◦ Median onset 48 days◦ Look for pre-exiting infections: crypto, PCP, TB

FEVER OF UNKNOWN ORIGIN

First described by Petersdorf and Beeson, 1961

Analyzed 100 cases from “a northeastern hospital”

They defined a fever as being of unknown origin if patient had T>101F on several occasions over >3 weeks, for which no diagnosis has been reached despite 1 week of inpatient investigation

FUO

Mandell

Classic FUO

Goldman and Cecil’s Medicine

Drug-induced fever5% of cases of drug hypersensitivity reactions

Usually accompanied by exanthema, hepatic, renal or pulmonary dysfunction

Peripheral eosinophilia can be seen

Most common: beta-lactams, sulfonamides, anticonvulsants

“Patient has a fever, what do you want me to do?”

◦ Evaluate patient (History, Physical, ROS, Vitals)◦ blood cultures, urine cultures, look for the source, imaging. Tx choice based on host/suspected organism.

◦ Review previous cultures◦ Febrile while on antibiotics: What is missing in your coverage? Drug fever?

◦ Evaluate for non-infectious causes

Teaching points:

Teaching points: “This patient keeps having fever, and already got his Tylenol maximum for the day! Can you order cooling blanket for him?”

“I measured this patient temperature, and in one ear its 38.1 and the other one is 38.3? What should I do, which ear do you want me to measure temperature in?”