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Fever in ICU. Dr. Marwan Jabr Alwazzeh Assoc. Prof. of Medicine Consultant Internist/Infectious Diseases University of Dammam 02/04/2012. Why Fever In ICU?. Key Problem Requires Thoughtful Evaluation and Treatment. Increasing health care costs.

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fever in icu

Fever in ICU

Dr. MarwanJabrAlwazzeh

Assoc. Prof. of Medicine

Consultant Internist/Infectious Diseases

University of Dammam


why fever in icu
Why Fever In ICU?
  • Key Problem Requires Thoughtful Evaluation and Treatment.
  • Increasing health care costs.
  • Exposes patients to sometimes unnecessary invasive diagnostic procedures
  • Inappropriate use of antibiotics that promoting emergence of resistant microbes.
when we say fever in the icu patient
When we say “fever” in the ICU patient?
      • Definition of fever is Arbitrary.
      • Society of Critical Care Medicine and Infectious diseases society of America >38.3 °C (100.4°F).
  • Lower threshold for surgery and immunocompromised patients >38.0 °C (100.4°F).
significance of fever
Significance of Fever
  • Enhancing the resistance to infection
  • Temperature elevation enhances immune function by:
    • Increased antibody production
    • Promoting T-cell activation
    • Increased cytokine production
    • Stimulates neutrophil and macrophage function
significance of fever1
Significance of Fever
  • Beneficial effects of hot baths and malarial fevers in treating syphilis.
  • In Gram negative bacteremia, a positive correlation between maximum temperature on the day of bacteremia and survival.
  • Some pathogens such as Streptococcus pneumoniaeare inhibited by febrile temperatures.
significance of fever2
Significance of Fever
  • Most patients should not routinely receive empiric antipyretic medication.
  • Acute hepatitis may occur in ICU patients with reduced glutathione reserves (alcoholics, malnourished, etc.) who have received regular therapeutic doses of acetaminophen.
  • Aggressively treating fever in critically ill patients may lead to a higher mortality rate.
deleterious effects of fever
Deleterious Effects Of Fever
  • ↑↑ Cardiac Output
  • ↑↑ Oxygen Consumption (approx 10%/°C)
  • ↑↑ Carbon Dioxide Production
  • ↑↑ Energy Expenditure
accuracy of methods used for measuring temperature
Accuracy of methods used for measuring temperature
  • Most accurate
    • Pulmonary artery thermistor
    • Urinary bladder catheter thermistor
    • Esophageal probe
    • Rectal probe
  • Other acceptable methods in order of accuracy
    • Oral probe
    • Infrared ear thermometry
  • Other methods less desirable
    • Temporal artery thermometer
    • Axillary thermometer
    • Chemical dot


recommendations for measuring temperature
Recommendations for Measuring Temperature
  • Axillary, temporal artery, and chemical dot thermometers should not be used in the ICU
  • Rectal thermometers should be avoided in neutropenic patients
  • Whatever device chosen should be used in a manner that does not facilitate spread of pathogens by the instrument or the operator
treating fever per se
Treating Fever per se
  • Fever should be treated only in patients with:
    • Acute brain insults.
    • Limited cardiorespiratory reserve (ie, ischemic heart disease).
    • Temperature increases above 40°C (104°F)
causes of fever in icu
Causes of fever in ICU
  • Differential diagnosis influenced by patient population
    • Medical vs. Surgical
    • Immunocompromised vs. competent
    • Community vs. Nosocomial
    • Pediatric vs. Geriatric
main infectious causes
Main infectious Causes
  • Intravascular Devices infection and septicemia
  • Pulmonary Infections and ICU-Acquired Pneumonia.
  • Urinary Tract Infections.
  • Infectious Diarrhea.
  • Sinus infections.
  • Surgical Site Infections.
  • Central Nervous System Infection.
systemic inflammatory response syndrome
Systemic Inflammatory Response Syndrome
  • Tow or more of the following:
    • Temperature ≥38 °C or ≤36 °C
    • Heart rate ≥90 beats/min
    • Respirations ≥20/min or arterial Carbone dioxide tension (PaCO2) < 32 mm Hg
    • White blood cell count ≥12,000/mm3 or ≤4000/mm3 or >10% immature [band] forms
systemic inflammatory response syndrome1
Systemic Inflammatory Response Syndrome
  • Often noninfectious etiology found:
    • Pulmonary embolism
    • Myocardial infarction
    • Gastrointestinal bleeding
    • Acute pancreatitis
    • Cardiopulmonary bypass

SIRS with a presumed or confirmed infectious process

severe sepsis
Severe sepsis
  • Sepsis with one or more signs of organ failure:
    • Cardiovascular
    • Renal
    • Respiratory
    • Hepatic
    • Hematologic
    • Central nervous system
    • Metabolic acidosis
septic shock
Septic shock

Sepsis-induced hypotension, despite adequate fluid resuscitation, with presence of perfusion abnormalities

infectious causes
Infectious Causes
  • Not all patients with infections are febrile.
  • 10% of septic patients are Hypothermic.
  • 35% are normothermicat presentation.
  • Septic patients who fail to develop a temperature have a significantly higher mortality than febrile septic patients.
afebrile infected patients
Afebrile infected patients
  • Elderly
  • Open abdominal wounds.
  • Large burns
  • Extracorporeal membrane oxygenation (ECMO)‏
  • CHF
  • CRF or End-stage liver disease.
  • Continuous renal replacement therapy
  • Taking anti-inflammatory or antipyretic drugs 
how can i diagnose infection in absence of fever
How can I Diagnose Infection in absence of fever?
  • Unexplained hypotension
  • Tachycardia
  • Tachypnea
  • Confusion
  • Rigors
  • Skin lesions
  • Respiratory manifestations
  • Oliguria
  • Lactic acidosis
  • Leukocytosis
  • Leukopenia
  • Immature neutrophils (i.e., bands) of >10%
  • Thrombocytopenia
when should i be worried
When should I be worried?
  • Immunocopromized patient
  • Hemodynamic instability
  • Oliguria
  • Increasing lactate
  • Worsening conscious state
  • Falling platelet counts
  • Worsening coagulopathy.
catheter related bloodstream infection definition
Catheter-Related Bloodstream InfectionDefinition
  • A positive catheter culture 15 CFU with concomitant positive blood culture of the same organism.
  • No other identifiable source of infection.
local catheter related infection definition
Local Catheter-Related InfectionDefinition
  • Growth of 15 or more CFU from a catheter specimen by semiquantitative culture.
  • Local signs of inflammation: erythema, swelling, tenderness, purulent material.
  • Negative peripheral blood culture.
catheter related bloodstream infection
Catheter-Related Bloodstream Infection

Approximately 25% of central venous catheters become colonized, and approximately 20-30% of colonized catheters will result in catheter sepsis

suppurative phlebitis
Suppurative phlebitis
  • Most often encountered in burn patients or other ICU patients who develop catheter-related infection that goes unrecognized, permitting microorganisms to proliferate to high levels within an intravascular thrombus.
  • bloodstream infection characteristically persists after the catheter has been removed.
  • Clinical picture of overwhelming sepsis with high-grade bacteremia or fungemia or with septic embolization.
recommendations for obtaining blood cultures
Recommendations for Obtaining Blood Cultures
  • For patients without an indwelling vascular catheter, obtain at least 2 blood cultures using strict aseptic technique from peripheral sites by separate venipunctures after appropriate skin disinfection.
  • For patients with an indwelling vascular catheter Obtain 3-4 blood cultures.
recommendations for obtaining blood cultures1
Recommendations for Obtaining Blood Cultures
  • For cutaneous disinfection:
    • 2%chlorhexidinegluconate in 70% isopropyl alcohol
    • tincture of iodine is equally effective (30 sec. of drying time).
    • Povidine iodine is an acceptable alternative, but must wait greater than 2 minutes to dry.
recommendations for obtaining blood cultures2
Recommendations for Obtaining Blood Cultures
  • The injection port of the blood culture bottles should be wiped with 70-90% alcohol before injecting the blood sample into the bottle.
  • Most blood culture bottles should not be swabbed with iodine-containing antiseptics.
  • Draw 20-30ml of blood per culture.
  • Label the blood culture with the exact time, date, and anatomic site from which it was taken.
management of fever in icu
Management of fever in ICU
  • There is no evidence that the yield of cultures drawn from an artery is different from the yield of cultures drawn from a vein.
  • Catheter Cultures:
    • Short catheter: tip.
    • longer catheter: Tip and intracutaneous segment.
    • Pulmonary artery catheter: Tip and introducer.
    • It is rarely necessary to culture infusate specimens.
    • It is rarely necessary to culture infusate specimens.
  • Candida species are constituents of the normal flora in about 30% of all healthy people.
  • Antibiotic therapy increases the incidence of colonization by up to 70%.
  • Candida Infection should be considered in febrile ICU patients who have been in the ICU for ≥10 days and have received multiple courses of antibiotics.


  • Although candiduria may be observed in up to 80% of patients with systemic candidiasis, candidemia from a urinary tract source is extremely rare.
  • galactomannan and beta-D-glucan for aspergillosis and Candida may be useful as supportive evidence of infections but may be most useful to exclude invasive fungal infection, given their high negative predictive value.
catheter related blood stream infection cvc insertion bundle
Catheter Related Blood Stream InfectionCVC Insertion Bundle
  • Hand hygiene.
  • Maximal barrier precautions.
  • Chlorhexidine skin antisepsis.
  • Optimal catheter site selection, with avoidance of using the femoral vein for central venous access in adult patients.

The Canadian Collaborative, Safer Healthcare Now


Catheter Related Blood Stream InfectionCVC Maintenance Bundle

  • Daily review of line necessity and prompt removal of unnecessary lines.
  • Dedicated lumen for total parenteral nutrition (TPN).
  • Access the CVC lumens aseptically.
  • Checking entry site for inflammation with every change of dressing.

The Canadian Collaborative, Safer Healthcare Now

recommendations for evaluation of pulmonary infections
Recommendations for Evaluation of Pulmonary Infections
  • All radiographs should be performed in an erect sitting position, during deep inspiration if possible.
  • The absence of infiltrates, masses, or effusions does not exclude pneumonia, abscess, or empyema.
  • Obtain one sample of lower respiratory tract secretions for direct examination and culture before initiation of or change in antibiotics.
recommendations for evaluation of pulmonary infections1
Recommendations for Evaluation of Pulmonary Infections
  • Isolation of enterococci, viridans streptococci, coagulase-negative staphylococci, and Candidaspecies should rarely if ever be considered the cause of respiratory dysfunction.
  • Quantitative cultures can provide useful information in certain patient populations when assessed in experienced laboratories.
ventilator bundle
Ventilator Bundle
  • Elevate the Head of the bed to 30-45 degrees.
  • Peptic ulcer disease prophylaxis.
  • Deep venous thrombosis prophylaxis.
  • Provide mouth care every 2-4 hours.
  • Sedation vacation every day.
  • Repeated evaluation of the patient’s readiness to be weaned from the ventilator.
urinary tract infection1
Urinary Tract Infection
  • Pyuria may be absent in patients with catheter-associated urinary tract infection and, even if present, is not reliably predictive of infection or associated with symptoms referable to the urinary tract.
  • The rapid dipstick tests, which detect leukocyte esterase and nitrite, are unreliable tests in the setting of catheter-related urinary tract infection.
urinary tract infection2
Urinary Tract Infection
  • The concentration of urinary bacteria or yeast needed to cause symptomatic urinary tract infection or fever is unclear.
  • Bacteriuria with ≥ 105 CFUs of bacteria per milliliter of urine during bladder catheterization was associated with a 2.8-fold increase in mortality.
urinary tract infection3
Urinary Tract Infection
  • Patients with urinary catheters in place should have urine collected from the sampling port and not from the drainage bag.
  • Urine should be transported to the laboratory and processed within one hour to avoid bacterial multiplication.
  • Gram stains of centrifuged urine will reliably show the infecting organisms
uti bundle
UTI bundle
  • Use sterile technique at insertion
  • Perform a daily reviewof the need for the urinary catheter.
  • Provide perineal care on a daily basis and after every bowel movment.
  • Keep the drainage bag lower than patient's bladder at all times.
  • Secure all catheters
c difficile associated diarrhea
C.Difficileassociated diarrhea
  • May occur with any antibacterial agent, but the most common causes are clindamycin, cephalosporins, and fluoroquinolones.
  • some patients with C.difficileespecially those who are postoperative, may present with ileus or toxic megacolon or leukocytosiswithout diarrhea.
c difficile associated diarrhea2
C.difficile–associated diarrhea
  • Cultures for C. difficilerequire 2 to 3 days for growth, and are not specific in distinguishing toxin-positive strains, toxinnegative strains, and asymptomatic carriage.
  • Infection with Klebsiellaoxytocashould be considered in patients who are negative for C. difficile.
  • Acute neutropenicenterocolitisor typhlitis should be sought in cancer or stem cell transplant.
  • Accounts for about 5% of nosocomial ICU infections.
  • Polymicrobial infection in up to 50% of cases, reflecting ICU flora.
  • Fever and Leucocytosis often present.
  • Purulent nasal discharge often lacking.
  • Sinus opacification by plain radiography is sensitive but nonspecific for the diagnosis.
  • CT the modality of choice if clinical evaluation suggests that sinusitis may be a cause of fever.
  • Risk factors:
    • Naso-tracheal tubes (incidence of up to 85% after a week of intubation).
    • Naso-gastric tubes.
    • nasal packing.
    • facial fractures.
    • steroid therapy.
surgical site infections
Surgical Site Infections
  • Examine the surgical incision at least once daily.
  • If there is suspicion of infection, the incision should be opened and cultured.
surgical site infections1
Surgical Site Infections
  • Tissue biopsies or aspirates are preferable to swabs.
  • Superficial swab cultures are likely to be contaminated with commensal skin flora and are not recommended.
surgical site infection prevention bundle
Surgical Site Infection Prevention Bundle
  • Appropriate use of Antibiotics.
  • Appropriate hair removal.
  • Preoperative glucose control in all diabetic patients.
  • Preoperative normothermia.
postoperative fever 5 ws
Postoperative fever5 Ws
  • Wind (atelectasis/pneumonia)
  • Water (UTI)
  • Walk (DVT-PA)
  • Wound (infection)
  • Wonder (drug reaction)
postoperative fever1
Postoperative fever
  • Fever is a common occurrence during the first 48 hrs post OP, usually noninfectious in origin.
  • Fever after 96 hrs post OP usually represents infection.
  • Early wound infections (2-48hrs post OP): Streptococcus or Clostridium.
noninfectious fever1
Noninfectious fever
  • For unknown reasons, most noninfectious disorders usually do not lead to a fever>102°F (38.9°C).
  • Exceptions:
    • Drug fever
    • Transfusion reaction
    • Neoplasm
    • Malignant hyperthermia
    • Neuroleptic malignant syndrome
noninfectious causes
Noninfectious causes
  • Acalculouscholecystitis
  • Acute myocardial infarction
  • Adrenal insufficiency
  • Blood product transfusion
  • Cytokine-related fever
  • Dressler syndrome
  • Drug related fever
  • Fat emboli
  • Fibroproliferative phase of acute respiratory distress syndrome
  • Gout
  • Heterotopic ossification
  • Immune reconstitution inflammatory syndrome
  • Intracranial bleed
  • Jarisch-Herxheimer reaction
  • Pancreatitis
  • Pulmonary infarction
  • Pneumonitis without infection
  • Stroke
  • Thyroid storm
  • Transplant rejection
  • Tumor lysis syndrome
  • Venous thrombosis
acalculous cholecystitis1
  • Occurs in approx 1.5% of critically ill (↑incidence), Potentially life threatening, frequently unrecognized.
  • Complex pathophysiology: G B ischemia, bile stasis, prolonged fasting, positive-end expiratory pressure, parenteral nutrition and sustained narcotic therapy).
  • High rate of gangrene and perforation.
  • Should be considered in any post OP or acutely ill patient with upper abdominal pain, fever or leukocytosis.
acalculous cholecystitis2
  • US 90% Specific 100% Sensitive:
    • ↑ wall thickness (>3mm)
    • intramural lucencies
    • GB distension
    • pericholecystic fluid
    • intramural sludge
  • Treatment:
    • Nonoperativepercutaneous drainage successful 80-90%.
    • Open cholecystectomy remains treatment of choice.
  • Mortality 15-30%.
drug related fever pathogenesis
Drug related feverPathogenesis
  • Hypersensitivity reaction.
  • Local inflammation at the site of administration : (Amphotericin B, erythromycin, KCl, sulfonamides & cytotoxic chemotherapies)
  • Drugs or their delivery systems may contain pyrogens or microbial contaminants.
  • Stimulation of heat production: (e.g. thyroxine)
  • Limit heat dissipation: (e.g., atropine)
  • Alter thermoregulation : (e.g., phenothiazines, antihistamines , anti-parkinsonian drugs).
drug related fever1
Drug-Related Fever
  • Rash occurs in a small fraction of cases.
  • Eosinophilia is also uncommon.
  • Among drug categories:
    • Antimicrobials (especially B-lactam drugs).
    • Antiepileptic drugs (especially phenytoin).
    • Antiarrhythmics (especially quinidine, procainamide).
    • Antihypertensives (methyldopa).
  • Fever induced by drugs may take several days to resolve 3-7.
drug related fever2
Drug-Related Fever
  • Withdrawal of certain drugs may be associated with fever, often with associated tachycardia, diaphoresis, and hyperreflexia.
  • Alcohol, opiates (including methadone), barbiturates, and benzodiazepines have all been associated with this febrile syndrome.
  • Withdrawal and related fever may occur several hours or days after admission.
drug related fever malignant hyperthermia
Drug-Related FeverMalignant Hyperthermia
  • Due to genetic predisposition and exposure to succinylcholine or inhaled anesthetic agents.
  • Autosomal-dominant abnormality of the skeletal muscle membrane (1:50000).
  • Pathophysiology: massive efflux of calcium from skeletal muscle sarcoplastic reticulum.
  • Patients may undergo several operations safely before MH crisis occurs.
drug related fever malignant hyperthermia1
Drug-Related FeverMalignant Hyperthermia
  • Onset can be delayed for as long as 24 hrs, especially if the patient is on steroids.
  • Body temp increases rapidly ,along with muscle rigidity, tachycardia and increase CPK.
  • Dantrolene2 mg/kg q 5 minutes for a total dose of 10mg.
  • Monitor for myoglobinuria and renal failure.
  • 10-30% mortality.
drug related fever neuroleptic malignant syndrome
Drug-Related Fever Neuroleptic malignant syndrome
  • Rare but more often identified in the ICU than malignant hyperthermia.
  • It has been strongly associated with phenothiazines, thioxanthenes, andbutyrophenones.
  • In the ICU, haloperidol is perhaps the most frequently reported drug.
  • Use of droperidol and metoclopramide also has been reported.
  • The initiator of muscle contraction is central (increased levels of dopamine because of blockade of dopaminergic receptors).
drug related fever neuroleptic malignant syndrome1
Drug-Related Fever Neuroleptic malignant syndrome
  • Risk factors:
    • Dehydration
    • Alcoholism
    • Prior brain injury
    • Use of rapid neuroleptic
drug related fever neuroleptic malignant syndrome2
Drug-Related Fever Neuroleptic malignant syndrome
  • High fever, extrapyramidal symptoms such as lead pipe rigidity, hypercapnea, catatonia, stupor, rigidity, autonomic instability, tremor and rhabdomyolysis.
  • Treatment:
    • Cessation of antipsychotic medication
    • Active cooling
    • Hemodynamic support
    • Dopamenergic agonists (amantadine, bromocriptine)
    • Dantrolene
serotonin syndrome
Serotonin syndrome
  • Caused by large number of medication either alone in high dose or in combination.
  • increasingly seen with selective serotonin reuptake inhibitors in the treatment of various psychiatric disorders.
serotonin syndrome1
Serotonin syndrome
  • Characterized by altered mental status, fever, agitation, myoclonus, ataxia.
  • The serotonin syndrome may be exacerbated with concomitant use of linezolid.
  • Treatment supportive and the serotonin blocker syproheptadine my be of benefit.
management of fever in icu1
Management of fever In ICU
  • Clinical assessment of new fever should replace automatic, standing-order laboratory and radiologic tests in the ICU.
  • Serum procalcitoninlevels and endotoxin activity assay can be employed as an adjunctive diagnostic tool for discriminating infection as the cause for fever or sepsis presentations.