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Fever in a critically ill patientDr P Gautam, MD, ABIM

The American College of Critical Care Medicine and the Infectious Diseases Society of America defined fever as a body temperature of 38.3C (101F) or higher

High index of suspicion is required (can use lower temperature to define fever)DiabeticImmunocompromisedElderlyiv drug abuserschronic alcoholicspeople on chronic steroidsimmuno modulating agents

Infectious causesVentilator associated pneumoniaCatheter related blood stream infectionsUrosepsisIntra-abdominal infectionsSinus infectionsDiarrhoeaSurgical site infections

Drug feverDiagnosis is difficult as its a diagnosis of exclusionTemporal relationship of the fever to starting and stopping the drugAntibiotics, anti-epileptics, anti-arrhythmics, anti-hypertensivesSyndromesMalignant hyperthermiaNeuroleptic malignant syndromeSerotonin syndromeAlcohol or drug (ex- opioid, benzo) withdrawal

Pneumonia

HAP, HCAP, VAPVAP (ventilator associated pneumonia) is usually suspected when a patient who has been receiving mechanical ventilation for more than 48 hours develops a fever.

VAP is accompanied by -new or progressive pulmonary infiltrateleukocytosispurulent tracheobronchial secretions

VAPThese signs may be accompanied by an increased respiratory rate, increased minute volume, decreased tidal volume, decreased oxygenation, or the need for more ventilatory support or inspired oxygen

Post-operative feverPyretic response to surgery first 48 hrs post-op

"four Ws": wind (pulmonary causes: pneumonia, aspiration, and pulmonary embolism, but not atelectasis), water (urinary tract infection), wound (surgical site infection), "what did we do?" (iatrogenic causes: drug fever, blood product reaction, infections related to intravenous lines).

Surgical site infectionsShould be considered in any postoperative patient with a fever.

Most surgical site infections occur one to four weeks after surgery

Sinusitis

SinusitisSinusitis occurs in 8% of all ICU patients, but is more common among mechanically ventilated patients who have sinus opacification on imaging.

Fever without localizing symptoms and signs, since most patients are mechanically ventilated and unable to communicate the presence of a headache and sinus tenderness.

Purulent nasal drainage is occasionally present.

CT has better sensitivity than radiographs.

Sinus puncture and aspiration; tissue biopsy.

CAUTI

CAUTI Catheter-related urinary tract infections may present as a fever without localizing symptoms or signs.

They may also present with symptoms and signs of cystitis (fever, suprapubic pain, hematuria, pyuria), pyelonephritis (fever, chills, flank pain, costovertebral angle tenderness, nausea, and vomiting), or urosepsis.

Urinalysis and urine culture are indicated with a urethral catheter, urinary obstruction, renal calculi, recent genitourinary surgery or trauma, or Neutropenia

Catheter associated bacteriuria or candiduria represents colonization, rarely cause fever or bacteremia

Catheter Related Blood Stream Infection (CRSBSI)

CLABSI

Prevention of CLABSI

CRBSI (Catheter Related Blood Stream Infections)Present as a fever without localizing symptoms or signs.

Alternative presentations include cellulitis at the insertion site, purulent drainage from the insertion site, incidentally detected bacteremia, sepsis (fever, tachycardia, tachypnea, leukocytosis), severe sepsis (sepsis plus organ dysfunction), or septic shock (eg, severe sepsis plus shock).

Rarely, a patient may present with suppurative thrombophlebitis, endocarditis, or septic abscesses.

Transesophageal echocardiogram (TEE) should be pursued in the setting ofS. aureusbacteremia to rule out infective endocarditis (IE).

Blood cultures

Blood culturesOnly mandatory diagnostic test in ICU patient with a new fever.

Two or more sets (aerobic and anaerobic) of blood cultures are recommended before initiation of any new antimicrobial.

In potentially septic patients with an intravascular catheter (in place >48h) in whom a site of infection is not clinically apparent or a suspicion of intravascular catheter-associated infection exists, at least one blood culture set should be obtained from the catheter (along with simultaneous peripheral blood cultures).

Antibiotics (Sepsis Guidelines 2016)1. We recommend that administration of IV antimicrobials be initiated as soon as possible after recognition and within 1 h for both sepsis and septic shock (strong recommendation, moderate quality of evidence; grade applies to both conditions).

2. We recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage) (strong recommendation, moderate quality of evidence).

3. We recommend that empiric antimicrobial therapy be narrowed once pathogen identificationand sensitivities are established and/or adequate clinical improvement is noted (BPS).

Empiric antibiotics for new fever in ICUIf they are deterioratingIn shockNeutropenic or immunosuppressedHave a ventricular assist device New fever that is >38.9F (102F)

Antifungals?Risk factors for invasive Candida infections include immunocompromised status (neutropenia, chemotherapy, transplant, diabetes mellitus, chronic liver failure, chronic renal failure), prolonged invasive vascular devices (hemodialysis catheters, central venous catheters), total parenteral nutrition, necrotizing pancreatitis, recent major surgery (particularly abdominal), prolonged administration of broad-spectrum antibiotics, prolonged hospital/ICU admission, recent fungal infection, and multisite colonization

Biomarkers

C Reactive protein

CRP is a very nonspecific marker of sepsis. Changes in concentrations over time are more useful than single values.

Procalcitonin

May be particularly useful in distinguishing bacterial from other forms of infection.

Trends in concentrations over time are again of more value than single measurements.

Mortality rates were lower in patients whose PCT concentration decreased by more than 50% in 72 h than in those in whom levels decreased by less than 50% (12.2 vs 29.8%; p = 0.007).

Procalcitonin role (Sepsis Guidelines 2016) 14. We suggest that measurement of procalcitonin levels can be used to support shortening the duration of antimicrobial therapy in sepsis patients (weak recommendation, low quality of evidence).

15. We suggest that procalcitonin levels can be used to support the discontinuation of empiric antibiotics in patients who initially appeared to have sepsis, but subsequently have limited clinical evidence of infection (weak recommendation, low quality of evidence).

Procalcitonin and other biomarkersOnly supportive and supplemental data to clinical assessment.

Decisions on initiating, altering, or discontinuing antimicrobial therapy should never be made solely on the basis of changes in any biomarker, including procalcitonin.

Quick Sequential Organ Failure Assessment Score

New biomarkers Cytokine levelssTREM1CD64Clot waveform analysisGrowth arrest specific protein 6AngiopoietinuPARHLA

New biomarkersProtemics, Genomics and PCRSeptiFast (Roche Diagnostics, Mannheim, Germany) and VYOO (SIRS-LAB, Jena, Germany) enable identification of 2541 of the most common bacterial and fungal pathogens; SepsiTest (Molzym, Bremen, Germany) uses an all-pathogen approach to detect fungemia or bacteremia.

Combination panels of biomarkers or sepsis scores are likely to replace individual biomarker levels

TNM classification exists for staging malignancy

PIRO score for staging Sepsis?

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