Anas Naeem 8 May 2013 AN UNDERSTANDING & APPROACH TO FEVER IN THE ICU.

Anas Naeem8 May 2013

AN UNDERSTANDING & APPROACH TO FEVER IN THE ICU

DEFINITION

• Normal body temperature is approximately 37.0ºC

• Fever defined as a body temperature of 38.3ºC or higher

• It is reasonable to use a lower temperature to define fever in immunocompromised patients.

TEMPERATURE MEASUREMENT • Intravascular, intravesicular (e.g. bladder), rectal, and oral

• The gold standard is the thermistor on a pulmonary artery catheter, although these are used infrequently

• Regardless of which method is chosen, the same method and site of measurement should be used repeatedly to facilitate the trending of serial measurements

• Alternative methods, such as axillary, temporal artery, tympanic, and chemical dot monitors, should not be used because they are inaccurate during critical illness

EPIDEMIOLOGY

EPIDEMIOLOGY

• Fever complicates up to 70% of all ICU admissions

• Increased length of stay, increased cost of care, and poorer outcomes

• May prompt unnecessary investigations and lead to inappropriate antibiotic use.

Significance of Fever

Julius Wagner-Jauregg (in black jacket) watching the transfusion of blood from a patient with malaria to a patient with neurosyphilis, to trigger fever. This approach won Wagner –Jauregg the 1927 Nobel Prize in Medicine

Significance of FeverThe beneficial effects…

• An adaptive response that has evolved to help rid the host of invading pathogens

• Enhance several parameters of immune function

• Some pathogens such as strep pneumoniae are inhibited by febrile temperatures

Significance of FeverThe harmful effects…

• Increase in cardiac output, oxygen consumption, carbon dioxide production and energy expenditure.

• Poorly tolerated in patients with limited cardiorespiratory reserve

• In traumatic head injury moderate elevation of brain temperature may markedly worsen the resulting injury

Fever Patterns

• May provide some diagnostic clues

• > 48 h after mechanical ventilation secondary to a developing pneumonia

• 5 to 7 days postoperatively may be related to abscess formation

• 10 to 14 days post antibiotics for intra-abdominal abscess may be due to fungal infections

DIFFERENTIAL DIAGNOSIS • Infectious or non infectious

• Distinguishing between infectious and noninfectious fevers is challenging

• The magnitude of the fever may be helpful

• Fevers between 38.3ºC and 38.8ºC may be infectious or non infectious. The differential diagnosis is longest in this range; fortunately, most non infectious sources of fever can be excluded by a detailed history and physical examination

DIFFERENTIAL DIAGNOSIS • Fevers between 38.9 and 41ºC can be assumed to be

infectious

• Fevers ≥41.1ºC (106ºF) are usually non infectious

Drug fever Transfusion reactions Adrenal insufficiency Thyroid storm Neuroleptic malignant syndrome Heat stroke Malignant hyperthermia

Infectious Causes • Ventilator-associated pneumonia

• Intravascular catheter-related infections

• Surgical site infections

• Catheter-related urinary tract infections

• Bacteremia from these and other sources

• Sinusitis

Infectious Causes Ventilator-associated pneumonia (VAP)

• Patient who has been receiving mechanical ventilation for more than 48 hours

• Decreased oxygenation• Decreased tidal volume• Increased minute volume• Increased respiratory rate• Purulent tracheobronchial secretions• New or progressive pulmonary infiltrate,• leukocytosis

Infectious Causes Intravascular catheter-related infection

• Commonly present as a fever without localizing symptoms or signs.

• A cellulitis at the insertion site• Purulent drainage from the insertion site• Incidentally detected bacteremia• Rarely, a patient may present with suppurative

thrombophlebitis, endocarditis, or septic abscesses.

Infectious Causes Surgical site infection

• Should be considered in any post-operative patient

• Most surgical site infections occur one to four weeks after surgery, although they may occasionally occur during the first postoperative week or more than a month after surgery.

• The clinical manifestations and likely pathogen depend upon the surgical site

Infectious Causes Catheter-related urinary tract infections • The incidence of catheter-related urinary tract

infections has probably been overestimated because many studies did not distinguish asymptomatic bacteriuria from a genuine urinary tract infection

• 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

Infectious Causes Bacteremia

May be secondary to any of the above infections, as

well as many others.

Fever may be the only sign of bacteremia

It can rapidly progress to sepsis, severe sepsis, or septic shock

Transfusion-transmitted bacterial infection is a rare, but life-threatening, complication of hospital care that does not always occur during transfusion

Infectious Causes Sinusitis

Occurs in 8% of all ICU patients More common among mechanically ventilated patients

who have sinus opacification on imaging It most typically manifests as 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

Infectious Causes Candida infections

7% of all nosocomial infections

Should be considered in febrile patients who have been in ICU > 10 days with multiple courses of antibiotics

Most ICU patients colonized with candida species

Isolation of Candida from urine/pulmonary samples usually represents colonization rather than infection

Infectious Causes

Other causes Cellulitis Cholangitis Diverticulitis Empyema Endocarditis Intra-abdominal abscess

Meningitis Myonecrosis Necrotizing fasciitis Pseudomembranous colitis Septic arthritis Suppurative

thrombophlebitis

Noninfectious Causes

In most cases the fever is not the only sign

The cause can usually be identified with a detailed history and physical examination

The role of atelectasis as a cause of fever is unclear; however, atelectasis probably does not cause fever in the absence of pulmonary infection

The non infectious causes of fever may be conceptualized as those that are accompanied by distributive shock and those that are not

Non infectious Causes Non-hemolytic transfusion reaction

Fever is the most common sign

It generally occurs within one to six hours after the initiation of a transfusion of red blood cells or platelets and may be accompanied by chills and mild dyspnea

Non-hemolytic reactions are benign with no lasting sequelae, but can be uncomfortable

Noninfectious Causes Drug fever Drug fever is a diagnostic challenge

It can occur several days after the initiation of the drug, can take several days to subside after cessation of the drug, and can produce high fevers (>38.9ºC) without other signs.

The true incidence is unknown

It is essentially a diagnosis of exclusion unless other signs of hypersensitivity (eg, rash) are present

Noninfectious Causes Acalculous cholecystitis Generally presents with fever, leukocytosis, and vague

abdominal discomfort

A right upper quadrant mass may be palpable

An insidious presentation is associated with gallbladder gangrene and perforation

Acalculous cholecystitis may have a mortality rate as high as 30 to 40 percent, even with treatment

Noninfectious Causes Mesenteric ischemia

Fever is a late sign in both arterial and venous

mesenteric ischemia It usually signifies bowel infarction, by which time

other signs have usually developed such as abdominal tenderness, hematochezia, or lactic acidosis

ARDS

Fever and leukocutosis may result from the inflmmatory-fibrotic process present in the airspace of patients with ARDS

Non infectious Causes Acute pancreatitis

Abdominal pain, distension, nausea and vomiting

Deep vein thrombosis (DVT) DVT is common among ICU patients, with an incidence

that has been estimated to be 12 to 33 % depending upon the patient populations studied and type of prophylaxis

DVT is a rare cause of fever. More common manifestations of DVT include asymmetric extremity edema, pain, or erythema

Non infectious Causes Pulmonary embolism (PE)

The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study about PE in hospitalized patients (not necessarily ICU patients) detected fever with the following frequency:

14% when defined as >37.8ºC (>100ºF) 6% when defined as >38.3ºC (>101ºF) 1.5% when defined as >38.9ºC (>102ºF)

Noninfectious Fever with Shock

Adrenal crisis (ie, acute adrenal insufficiency)

Thyroid storm

Acute haemolytic transfusion reaction.

The fever is often >38.9ºC and the shock is distributive, which is characterized by hypotension, warm extremities, oliguria, altered mental status, and metabolic acidosis

Noninfectious Fever with Shock Adrenal crisis In patients with previously undiagnosed adrenal

insufficiency who are subjected to a serious infection or other major stress

Patients with known adrenal insufficiency who do not take more glucocorticoid during a serious infection or other major stress,

Patients with acute bilateral adrenal infarction or hemorrhage

Patients whose chronic glucocorticoid therapy is abruptly withdrawn

Distributive shock is the predominant manifestation of an adrenal crisis, but fever, nausea, vomiting, abdominal pain, weakness, fatigue, lethargy, hypoglycemia, confusion, or coma may also be present

Noninfectious Fever with Shock Thyroid storm

Severe, life-threatening thyrotoxicosis

It is often precipitated by an acute stressor, such as surgery, infection, trauma, or an acute iodine load

Clinical manifestations may include severe fever (>40ºC), distributive shock, severe tachycardia (>140 beat/min), congestive heart failure, nausea, vomiting, diarrhea, agitation, delirium, psychosis, stupor, and coma

Noninfectious Fever with Shock Acute haemolytic transfusion reaction

• Is a medical emergency that results from the rapid destruction of donor red blood cells by recipient antibodies. It is usually due to ABO incompatibility

• Common clinical manifestations include fever, chills, distributive shock, disseminated intravascular coagulation, and acute kidney injury. Flank pain, red or brown urine, and bleeding occur less often

DIAGNOSTIC APPROACH

• Medical history and a full physical examination

• Blood cultures are the only mandatory diagnostic tests in patients with a new fever

• The rationale is that clinical findings cannot reliably exclude bacteremia and mortality is high without appropriate treatment

DIAGNOSTIC APPROACHLaboratory studies Transaminase, bilirubin, alkaline phosphatase,lipase,

and lactate measurements are indicated for patients with abdominal pain or whose abdominal exam cannot be reliably assessed due to sedation or coma.

Serum sodium, potassium, glucose, and cortisol levels should be drawn if adrenal insufficiency is possible

Thyroid stimulating hormone (TSH), T3, and T4 levels if thyroid storm is possible.

Direct antiglobulin test, plasma free hemoglobin, and haptoglobin, as well as a repeat blood type and cross-match if an acute haemolytic transfusion reaction is suspected.

DIAGNOSTIC APPROACH

Procalcitonin (PCT) is adjunctive diagnostic tools for distinguishing fever due to infection from noninfectious fever

C-reactive protein (CRP) it lacks specificity , rises later than PCT, doesn’t correlate as well with severity of disease , and tends to be lower among patients with liver disease

Both PCT and CRP predict mortality in ICU patients

DIAGNOSTIC APPROACH

Urinalysis and urine culture

Chest imaging

Abdominal imaging

Sinus evaluation:

Mechanically ventilated patients who have purulent nasal drainage or whose evaluation has otherwise been completely negative

Radiographic evaluation looking for sinus opacification, CT is the preferred modality

Culture of sinus fluid obtained by endoscopic-guided middle meatal aspiration is indicated for patients with sinus opacification and no other cause for fever

MANAGEMENT

Whether or not empiric antibiotic therapy is warranted

Patients who are deteriorating, in shock, neutropenic, or have a ventricular assist device

Patients who have a temperature ≥38.9ºC because most fevers in this range will be infectious

MANAGEMENT

Whether or not to routinely remove an intravascular catheter

Controversial and evolving issue

Considerations in the decision include: The severity of illness Age of the catheter Probability that the catheter is the source of fever

MANAGEMENT Fever itself does not generally require treatment with

antipyretics (eg, acetaminophen) or external cooling

Some evidence suggests that the use of antipyretics

may worsen outcomes in sepsis

Exceptions to this are when the fever may be detrimental to the outcome (eg, increased intracranial pressure), limited cardiorespiratory reserve or temperature ≥41ºC

If body temperature exceeds the “critical thermal maximum”, which is thought to be between 41.6ºC and 42ºC, life-threatening complications can ensue (eg, rhabdomyolysis)

Things to keep in Mind

1. Critically ill patients often have more than one infection.

2. Evidence of infection and inflammation (eg, leukocytosis, pus) may be altered if the patient is immunosuppressed.

3. Medical technologies (eg, continuous renal replacement therapy, extracorporeal membrane oxygenation [ECMO]) can modify or mask a fever.