Evaluation and Evaluation and Management of Management of

Fever in the Fever in the Critically-Ill Critically-Ill

Patient.Patient.David Oxman MDDavid Oxman MD

Assistant Professor of MedicineAssistant Professor of MedicineDivision of Pulmonary & Critical Care Division of Pulmonary & Critical Care

MedicineMedicineThomas Jefferson UniversityThomas Jefferson University

Fever in the ICUFever in the ICU Fever very common in the critically Fever very common in the critically

ill.ill. Can be symptom of life-threatening Can be symptom of life-threatening

illness or relatively harmless illness or relatively harmless process.process.

Competing concerns:Competing concerns: Not delaying diagnosis and Not delaying diagnosis and

treatment.treatment. Not performing unnecessary tests Not performing unnecessary tests

and proceduresand procedures

Pathophysiology of FeverPathophysiology of Fever Fever complex response to many disparate Fever complex response to many disparate

diseases.diseases. Febrile response not only includes elevation of Febrile response not only includes elevation of

body temp. but activation of physiological, body temp. but activation of physiological, endocrinologic and immunologic systems.endocrinologic and immunologic systems.

Neural regulation of body temperature involves Neural regulation of body temperature involves several different parts of the brain but several different parts of the brain but preoptic preoptic and anterior regions of the hypothalamusand anterior regions of the hypothalamus have have greatest rolegreatest role

Pyrogens – either endogenous or exogenous –Pyrogens – either endogenous or exogenous –stimulate cytokines (such stimulate cytokines (such IL-1, IL-6, TNF-α, IL-1, IL-6, TNF-α, IFN-γIFN-γ) or act directly on hypothalamic neurons) or act directly on hypothalamic neurons decrease their firing rate decrease their firing rate Leads to physiological responses that Leads to physiological responses that

decrease heat loss and increase heat decrease heat loss and increase heat production. production.

Das Verhalten der Eingenwarme in Krankenheiten

“The Behavior of Self-Warmth in Diseases”

Wunderlich

1 million 1 million observations in observations in 25,000 subjects.25,000 subjects.

Mostly axillary Mostly axillary temps and no more temps and no more than twice/day.than twice/day.

Called 98.6 or 37 C Called 98.6 or 37 C normal.normal.

100.4 or 38.0 C as 100.4 or 38.0 C as upper limit normal.upper limit normal.

Definitions of FeverDefinitions of Fever Definition fever somewhat arbitrary.Definition fever somewhat arbitrary. Study of healthy volunteers Study of healthy volunteers ((Mackowiak, Mackowiak,

JAMA 1992)JAMA 1992) Temperatures ranged from 35.6 C (96.0F) Temperatures ranged from 35.6 C (96.0F)

to 38.5C (100.8) to 38.5C (100.8) Mean of 36.8 Mean of 36.8 ++ 0.4C (98.2 0.4C (98.2 ++ 0.7 F) 0.7 F)

SCCM defines fever in as temp. > 38.3 SCCM defines fever in as temp. > 38.3 ((>>101F)101F)

Reasonable to use lower threshold for Reasonable to use lower threshold for immuno-suppressed and elderly. immuno-suppressed and elderly.

Measuring TemperatureMeasuring Temperature Conventional means includes Conventional means includes

intravascular, intravesical, rectal, oral, intravascular, intravesical, rectal, oral, and tympanic. and tympanic.

Axillary and tympanic are inaccurate Axillary and tympanic are inaccurate in critically ill patients and should not in critically ill patients and should not be used.be used.

The gold standard is the thermistor on The gold standard is the thermistor on a pulmonary artery catheter.a pulmonary artery catheter.

Whichever method is employed should Whichever method is employed should be used consistently and the site of be used consistently and the site of measurement documented. measurement documented.

How Common is Fever in How Common is Fever in ICU?ICU?

Retrospective cohort study by Retrospective cohort study by Laupland Laupland

>24,000 ICU admissions.>24,000 ICU admissions. Incidence of at least one Incidence of at least one

documented fever during ICU documented fever during ICU course was 44%.course was 44%.

Incidence of “high fever” (>39.5) Incidence of “high fever” (>39.5) only 8%.only 8%. Crit Care MedCrit Care Med, 2008, 2008

Laupland, Laupland, Critical Care MedicineCritical Care Medicine 2008 2008

Incidence of Fever by ICU Population

Fever Evaluation in Fever Evaluation in ICUICU

Main dilemma: infectious vs. Main dilemma: infectious vs. non-infectious causes.non-infectious causes.

Fever from infectious cause:Fever from infectious cause: generally treatablegenerally treatable worse outcomes if diagnosis worse outcomes if diagnosis

treatment delayed.treatment delayed. Fever from non-infectious Fever from non-infectious

cause: cause: often unmodifiable often unmodifiable not necessarily worse outcomes.not necessarily worse outcomes.

Causes of Fever in the Causes of Fever in the ICUICU

InfectiousInfectious Catheter infectionCatheter infection VAPVAP SinusitisSinusitis UTIUTI Wound InfectionWound Infection C. Difficile ColitisC. Difficile Colitis

Non-InfectiousNon-Infectious Post operativePost operative TransfusionsTransfusions Drug feverDrug fever Thromboembolic Thromboembolic

diseasedisease Acalculous cholecystitisAcalculous cholecystitis

Cerebral HemmorrhageCerebral Hemmorrhage ARDSARDS Adrenal insufficiencyAdrenal insufficiency Thyroid stormThyroid storm VasculitisVasculitis Atelectasis (?)Atelectasis (?) PancreatitisPancreatitis HematomaHematoma GoutGout ETOH withdrawlETOH withdrawl Tumor feverTumor fever BurnsBurns Myocardial InfarctionMyocardial Infarction

..and more !!!..and more !!!

The Fever Work-up MenuThe Fever Work-up Menu

Blood Cultures Blood Cultures Chest x-ray Chest x-ray Sputum examSputum exam Urinanalysis/cultureUrinanalysis/culture

LE ultrasound/CTA LE ultrasound/CTA CT sinuses CT sinuses

CT abdomen CT abdomen CT chest CT chest Lumbar punctureLumbar puncture

Right Upper Right Upper

Quadrant U/SQuadrant U/S White Blood Cell White Blood Cell

ScanScan Procalcitonin/CRPProcalcitonin/CRP ID ConsultID Consult

The “Fever Workup”The “Fever Workup”Perils & PitfallsPerils & Pitfalls

PerilsPerils Costly.Costly. Risk in procedures and tests.Risk in procedures and tests. Can lead to unnecessary Can lead to unnecessary

treatments.treatments. GoalGoal

Clinically appropriate to patient.Clinically appropriate to patient. Know strengths and weakness of Know strengths and weakness of

tests employed.tests employed.

Issues in Fever Issues in Fever Evaluation and Evaluation and ManagementManagement

Common Evaluation ProblemsCommon Evaluation Problems Ventilator-Associated PneumoniaVentilator-Associated Pneumonia Bacteremia/Intravascular Catheter InfectionBacteremia/Intravascular Catheter Infection Urinary Tract InfectionUrinary Tract Infection SinusitisSinusitis MeningitisMeningitis DVT/PEDVT/PE

Treatment/Outcomes of Fever in Treatment/Outcomes of Fever in Critically-illCritically-ill

Ventilator-Associated Ventilator-Associated PneumoniaPneumonia

Common ICU-acquired infection.Common ICU-acquired infection. Suspected in intubated patient with fever Suspected in intubated patient with fever

infiltrate, leukocytosis, and purulent infiltrate, leukocytosis, and purulent secretions.secretions.

Difficult to diagnose definitivelyDifficult to diagnose definitively CXR in ICU patient non-specific.CXR in ICU patient non-specific. Upper respiratory tract colonized with Upper respiratory tract colonized with

bacteria.bacteria. Non-infectious reasons for worsened gas Non-infectious reasons for worsened gas

exchangeexchange Common cause of unnecessary antibioticsCommon cause of unnecessary antibiotics

Klompas, JAMA

Overdiagnosis of VAP

Bacteremia/Intravascular Bacteremia/Intravascular Catheter InfectionCatheter Infection

Important to diagnoseImportant to diagnosePotentially life-threatening Potentially life-threatening conditioncondition

Generally easily treatableGenerally easily treatable DifficultiesDifficulties

Blood cultures not particularly Blood cultures not particularly sensitivesensitive

Contamination leads to false Contamination leads to false positivespositives

Newer technologies (e.g. PCR) Newer technologies (e.g. PCR) may improve sensitivitymay improve sensitivity

Bacteremia: Perils and Bacteremia: Perils and PitfallsPitfalls

Draw Draw beforebefore initiation of antibiotics initiation of antibiotics Don’t draw through peripheral IV: 3x Don’t draw through peripheral IV: 3x

the false positive rate!!!the false positive rate!!! Draw proper number - Never draw one Draw proper number - Never draw one

set!set! Draw proper volume: minimum 10ml Draw proper volume: minimum 10ml

but 20 preferred.but 20 preferred. Try not to draw through intravascular Try not to draw through intravascular

device (unless indicated).device (unless indicated). Consider more than two sets of Consider more than two sets of

patients with high pretest probability.patients with high pretest probability.

Detection of FungemiaDetection of Fungemia

Not necessary for routine use. Candida species grow well on

routine bacterial culture media.

Consider in immunocompromised patients at risk of uncommon fungal (e.g cryptococcus, fusarium) or mycobacterial bloodstream infection.

Fungal IsolatorFungal Isolator

Evaluation of Urinary Tract Evaluation of Urinary Tract InfectionInfection

UTIs reported to be common UTIs reported to be common in ICUin ICU

But no consistent definition But no consistent definition – most studies equate – most studies equate isolation of bacteria/yeast isolation of bacteria/yeast with infection.with infection.

Genuine UTIs in ICU Genuine UTIs in ICU probably uncommon.probably uncommon.

SCCM Guidelines 2008SCCM Guidelines 2008

““Cultures from catheterized Cultures from catheterized patients showing >10patients showing >103 3 cfu/mL cfu/mL represent true bacteruria or represent true bacteruria or candiuria, candiuria, but neither higher but neither higher countscounts, nor the presence of , nor the presence of pyuriapyuria alone are of much value in alone are of much value in determining if (this) is cause of a determining if (this) is cause of a patient’s fever; patient’s fever; in most cases, it is in most cases, it is not the cause of fevernot the cause of fever (level1).” (level1).”

Urinary Tract Infection: Urinary Tract Infection: Take HomeTake Home

Routine evaluation in febrile ICU Routine evaluation in febrile ICU patient of questionable benefit. patient of questionable benefit.

UA/culture hard to interpret in UA/culture hard to interpret in catheterized patientcatheterized patient

Patients at high risk of complication Patients at high risk of complication with UTI (neutropenia, urinary with UTI (neutropenia, urinary obstruction, pregnancy) should have obstruction, pregnancy) should have testing and presumptive treatment.testing and presumptive treatment.

Everyone else: WHO KNOWS?Everyone else: WHO KNOWS?

SinusitisSinusitis

SinusitisSinusitis

True incidence hard to knowTrue incidence hard to know Many ICU patients have fluid Many ICU patients have fluid

in sinusesin sinuses How many ICU patients with How many ICU patients with

fever are DUE TO sinusitis?fever are DUE TO sinusitis?

SinusitisSinusitis Hospital-acquired sinusitis is a common cause of fever of unknown origin in orotracheally intubated critically ill patients.

(Critical Care 2005 R583-R590. ) OR

Occult fever in surgical intensive care unit patients is seldom caused by sinusitis.

(Am J Surg 1992; 164 (5):412-5)

Diagnosis of SinusitisDiagnosis of Sinusitis

• Difficult to diagnose Difficult to diagnose in ICU patients.in ICU patients.

• Clinical signs Clinical signs symptoms not symptoms not reliablereliable

• Fluid in sinuses Fluid in sinuses common common

• Nasal swabs not Nasal swabs not diagnosticdiagnostic

• Aspiration of Aspiration of sinuses rarely donesinuses rarely done

Nosocomial Sinusitis in Nosocomial Sinusitis in Patients in the Medical Patients in the Medical

Intensive Care Unit:Intensive Care Unit:A Prospective Epidemiological A Prospective Epidemiological

StudyStudyGeorge, CID 1998George, CID 1998

366 intubated patients with fever 366 intubated patients with fever and/or purulent nasal dischargeand/or purulent nasal discharge

All patients with radiographic signs All patients with radiographic signs of sinus fluid had maxillary sinus of sinus fluid had maxillary sinus aspiration.aspiration.

28 (7.6%) met criteria for sinusitis28 (7.6%) met criteria for sinusitis RR of nasoenteric feeding RR of nasoenteric feeding withwith

orotracheal intubation 26.7 (3.7-orotracheal intubation 26.7 (3.7-194.5) <.0001194.5) <.0001

Sinusitis: Take HomeSinusitis: Take Home Sinusitis is common in critically-ill Sinusitis is common in critically-ill

patientspatients Common cause of FUO in critically-ill: ???Common cause of FUO in critically-ill: ??? High risk patients: High risk patients:

nasoenteric feeding with oral intubationnasoenteric feeding with oral intubation facial traumafacial trauma immunocompromised (fungal)immunocompromised (fungal)

Treatment:Treatment: removal nasoenteric tuberemoval nasoenteric tube decongestantsdecongestants brief course antibioticsbrief course antibiotics

Meningitis in the ICU or Meningitis in the ICU or “Do I “Do I have to have to LP all my patients LP all my patients

with fever.”with fever.”• Dyad of fever Dyad of fever

and altered and altered mental status mental status very common very common in ICU.in ICU.

• Teaching: “If Teaching: “If you think you think about LP, do about LP, do one”one”

• Tremendous Tremendous variability in variability in diagnostic diagnostic practice.practice.

What’s the Data Say?What’s the Data Say? Addelson-MittyAddelson-Mitty 1 1: :

70 non-neurosurgical SICU patients70 non-neurosurgical SICU patients Most LPs performed to evaluate Most LPs performed to evaluate

fever and mental status change fever and mental status change (“r/o meningitis”)(“r/o meningitis”)

No cases meningitis diagnosed.No cases meningitis diagnosed. Metersky Metersky 22

52 LPs to rule out nosocomial 52 LPs to rule out nosocomial meningitismeningitis

None positiveNone positive 1. Addelson-Mitty, 1. Addelson-Mitty, Intensive Care MedIntensive Care Med 1997 1997 2. Metersky. Clinical Infectious Diseases 19972. Metersky. Clinical Infectious Diseases 1997

LP for Fever in ICU:LP for Fever in ICU:Take HomeTake Home

ICU-acquired meningitis very rare. ICU-acquired meningitis very rare. Data does not support routine LP for ICU-Data does not support routine LP for ICU-

acquired fever/altered mental status.acquired fever/altered mental status. Exceptions:Exceptions:

Neurosurgical patients.Neurosurgical patients. Intracranial device.Intracranial device. Severe immune compromise (including Severe immune compromise (including

cancer).cancer). ? Undiagnosed community-acquired? Undiagnosed community-acquired

DVT/PE as Cause of DVT/PE as Cause of Fever in the ICUFever in the ICU

DVT common in ICU patients DVT common in ICU patients (10-30%)(10-30%)

But how common is DVT/PE But how common is DVT/PE as as

causecause of fever. of fever.

Clinical DataClinical Data

Fever and DVT RIETE Registry >14,000 patients with

DVT 707 (4.9%) with temp >38 C. at

presentation ??? % with other signs of DVT

AbuRhama (Surgery 1997) 114 Duplexes for FUO DVT considered cause of FUO in 5 (6%) $450 x 144 = $51,300 ; $10,260 per

case DVT

PIOPEDPIOPED 311 with angiographically proven 311 with angiographically proven

pulmonary embolism.pulmonary embolism. 43 (14%) had temp > 100.0 and 43 (14%) had temp > 100.0 and

no other cause.no other cause. 19 (6.1 %)) had temp >38.3ºC 19 (6.1 %)) had temp >38.3ºC

and no other source. and no other source. 5 (1.6 percent) had a 5 (1.6 percent) had a

temperature of >38.9ºC. temperature of >38.9ºC.

DVT/PE Bottom LineDVT/PE Bottom Line

In ICU patients with FUO In ICU patients with FUO and and no other sign of no other sign of thromboembolic diseasethromboembolic disease, , DVT/PE examination low DVT/PE examination low yield.yield.

Might be useful to knowMight be useful to know Cost-effective ??Cost-effective ??

Does Magnitude of Fever Does Magnitude of Fever Mean Anything?Mean Anything?

High fever definition varies, often High fever definition varies, often greater than 39.5 (103F).greater than 39.5 (103F).

? more likely in certain conditions.? more likely in certain conditions. <102 - ??????<102 - ?????? 102-106: 102-106:

? more commonly infection? more commonly infection Laupland: more culture + patients.Laupland: more culture + patients.

>106 : >106 : likely non-infectiouslikely non-infectious Patients do worsePatients do worse

Empiric AntibioticsEmpiric Antibiotics Not every fever needs new antibiotic! Not every fever needs new antibiotic! Those who do: High risk of bad outcomeThose who do: High risk of bad outcome

Deteriorating conditionDeteriorating condition Incipient ShockIncipient Shock

Compromised HostCompromised Host neutropenicneutropenic ventricular assist deviceventricular assist device

Fever ≥102ºF (as most infectious) ????Fever ≥102ºF (as most infectious) ???? For other patients with new fever For other patients with new fever

WAITWAIT

In Defense of FeverIn Defense of Fever

Fever itself typically seen as Fever itself typically seen as harmful to patient.harmful to patient.

Yet questionable evidence if Yet questionable evidence if treating fever beneficial.treating fever beneficial.

Could treating fever be bad Could treating fever be bad for patient?for patient?

In Defense of FeverIn Defense of Fever

Highly preserved evolutionary Highly preserved evolutionary response.response.

Number of conditions where Number of conditions where fever associated with bad fever associated with bad outcomesoutcomes

Other situations could be Other situations could be beneficialbeneficial

Experimental DataExperimental DataProtective in mouse and sheep Protective in mouse and sheep models of sepsis.models of sepsis. induces heat shock response critical for cellular induces heat shock response critical for cellular

protectionprotection reduces endothelial and organ damage reduces endothelial and organ damage downregulates activity of NF-κB, modulating the downregulates activity of NF-κB, modulating the

immune responseimmune response

In vitro effect on antibiotics.In vitro effect on antibiotics. growth time bacteria prolongedgrowth time bacteria prolongedMIC reducedMIC reduced

Ozveri et al Intensive Care Med 1999, 25:1155-1159.Mackowiak , et al J Infect Dis 1982, 145:550-553.

Clinical DataClinical Data Uncontrolled and RetrospectiveUncontrolled and Retrospective

Higher survival from gram-negative Higher survival from gram-negative bacteremia in patients with fever bacteremia in patients with fever 11..

elderly patients with CAP > mortality elderly patients with CAP > mortality rate with no fever rate with no fever (29% vs. 4%) (29% vs. 4%) 22..

Prospective and ControlledProspective and Controlled 44 Trauma ICU patients 44 Trauma ICU patients 33.. Randomized to Randomized to treatment vs permissivetreatment vs permissive

fever.fever. 7 deaths in treatment vs 1 death permissive 7 deaths in treatment vs 1 death permissive

1. Bryant et al Arch Intern Med 1971, 127:120-1282. Ahkee et al SouthMed J 1997, 90:296-298.

3. Schulman et al. Surg Infect (Larchmt) 2005, 6:369-375.

Laupland CCM 2008Laupland CCM 2008

ICU FEVER AND MORTALITY

Bad Effects of Fever Bad Effects of Fever in ICU Patientin ICU Patient

Appears to worsen outcomes in Appears to worsen outcomes in traumatic brain injuries.traumatic brain injuries.

Increases cardiac output, O2 Increases cardiac output, O2 consumption and CO2 consumption and CO2 production.production.

Poorly tolerated in patients with Poorly tolerated in patients with low cardio-respiratory reserve.low cardio-respiratory reserve.

Specific hyperthermias (e.g. NMS, Specific hyperthermias (e.g. NMS, malignant hyperthermia, heat malignant hyperthermia, heat stroke) need treatment.stroke) need treatment.

Treatment of Fever: Take Treatment of Fever: Take HomeHome

Effect of fever on Effect of fever on outcomes unclearoutcomes unclear

Evidence that in infections Evidence that in infections may be beneficialmay be beneficial

Several specific conditions Several specific conditions where fever detrimental.where fever detrimental.

Overall ConclusionsOverall Conclusions Fever, especially low grade, is very common in Fever, especially low grade, is very common in

ICU patients.ICU patients. Unexplained fever merits some clinical Unexplained fever merits some clinical

assessment.assessment. Blood cultures perhaps only mandatory investigation.Blood cultures perhaps only mandatory investigation. Other tests should be appropriate to patientOther tests should be appropriate to patient

Important to know something about performance of test.Important to know something about performance of test. Interpret with entire clinical pictureInterpret with entire clinical picture

Many non-infectious causes have benign courseMany non-infectious causes have benign course Not every fever needs an antibioticNot every fever needs an antibiotic Treatment of fever only proven benefit in Treatment of fever only proven benefit in

specific populations.specific populations.

ReferencesReferences1.1. Circiumaru, et. al. Prospective study of fever in the intensive care Circiumaru, et. al. Prospective study of fever in the intensive care

unit. Intensive Care Med 1999: 25(7):668-73.unit. Intensive Care Med 1999: 25(7):668-73. 2.2. Mackowiak, et. al. Critical appraisal of 98.6F, the upper limit of Mackowiak, et. al. Critical appraisal of 98.6F, the upper limit of

normal body temperature, and other legacies of Carl Reinhold August normal body temperature, and other legacies of Carl Reinhold August Wunderlich; JAMA 1992:268 (12): 1578-80.Wunderlich; JAMA 1992:268 (12): 1578-80.

3.3. Kane, et. Al The detection of microbial DNA in the blood: a sensitive Kane, et. Al The detection of microbial DNA in the blood: a sensitive method for diagnosing bacteremia and/or bacterial translocation in method for diagnosing bacteremia and/or bacterial translocation in surgical patients. Ann Surg 1998 Jan;227(1):1-9surgical patients. Ann Surg 1998 Jan;227(1):1-9

4.4. Galicier and Richet. Prospective study of postoperative fever in a Galicier and Richet. Prospective study of postoperative fever in a general surgery department. Infect Control 1985: 6:487-90general surgery department. Infect Control 1985: 6:487-90

5.5. Engeron M. Lack of association between atelectasis and fever. Chest Engeron M. Lack of association between atelectasis and fever. Chest 1995: 107 (1): 81-4.1995: 107 (1): 81-4.

6.6. Kisala JM Am J Physiol Regul Integr Comp Physiol 264: R610-164 Kisala JM Am J Physiol Regul Integr Comp Physiol 264: R610-164 1993.1993.

7.7. Marik et. al. Incidence of deep venous thrombosis in ICU patients. Marik et. al. Incidence of deep venous thrombosis in ICU patients. Chest 1997: 111 (3): 661-4. Chest 1997: 111 (3): 661-4.

8.8. Fagon et. al. Evaluation of clinical judgement in identification and Fagon et. al. Evaluation of clinical judgement in identification and treatment nosocomial pneumonia in ventilated patients. Chest 1993; treatment nosocomial pneumonia in ventilated patients. Chest 1993; 102 (2):547-53102 (2):547-53

9.9. Fabregas, et. al. Clinical diagnosis of ventilator associated pneumonia Fabregas, et. al. Clinical diagnosis of ventilator associated pneumonia revisited. Thorax 1999; 54 (10):867-73revisited. Thorax 1999; 54 (10):867-73

10.10. Marik PE, Fever in the ICU. Chest 2000; 117;855-869.Marik PE, Fever in the ICU. Chest 2000; 117;855-869.11.11. Peres BD; Melot C, et al. Crit Care Med 2003 Nov;31(11):2579-84.Peres BD; Melot C, et al. Crit Care Med 2003 Nov;31(11):2579-84.

Infectious causes fever in Infectious causes fever in ICUICU

Prevalence of nosocomial Prevalence of nosocomial infection in ICU quoted as infection in ICU quoted as from 3-31%. from 3-31%. 88

True numbers difficult True numbers difficult because of varying definitions.because of varying definitions.

Strong correlation between Strong correlation between ICU length of stay and ICU length of stay and likelihood infection.likelihood infection.

Post-operative FeverPost-operative Fever

Well-recognized but poorly defined Well-recognized but poorly defined syndrome.syndrome.

Magnitude of trauma correlated Magnitude of trauma correlated with degree fever response.with degree fever response.

Cytokine release from tissue Cytokine release from tissue trauma.trauma.

? Elevated levels bacterial ? Elevated levels bacterial endotoxins and exotoxins.endotoxins and exotoxins.

Post-operative FeverPost-operative Fever

Prospective study 800 surgical Prospective study 800 surgical patients, 81 (9%) developed fever patients, 81 (9%) developed fever with no cause.with no cause.

Those with fever within 48 hours Those with fever within 48 hours much less likely to be infectious.much less likely to be infectious.

> 96 hours post-op infection > 96 hours post-op infection much more likely.much more likely.

Practice of deferring workup 48 Practice of deferring workup 48 hours probably soundhours probably sound..

Galicier and Richet. Infect Control 1985Galicier and Richet. Infect Control 1985