Dr. Marwan Jabr Alwazzeh Assoc. Prof. of Medicine Consultant Internist/Infectious Diseases...

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. 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? Definition of fever is Arbitrary. Society of Critical Care Medicine and Infectious diseases society of America >38.3 C (100.4F). Lower threshold for surgery and immunocompromised patients >38.0 C (100.4F).

Pathophysiology 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 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 pneumoniae are inhibited by febrile temperatures.

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. Significance 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 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 AccuracyAccuracy

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 Fever should be treated only in patients with: Acute brain insults. Limited cardiorespiratory reserve (ie, ischemic heart disease). Temperature increases above 40C (104F)

Causes of fever in ICU Differential diagnosis influenced by patient population Medical vs. Surgical Immunocompromised vs. competent Community vs. Nosocomial Pediatric vs. Geriatric

Causes of fever in ICU

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.

Fever In ICU

Infectious causes Definitions Septic shock Severe sepsis Sepsis Systemic inflammatory response syndrome (SIRS)

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 Syndrome Often noninfectious etiology found: Pulmonary embolism Myocardial infarction Gastrointestinal bleeding Acute pancreatitis Cardiopulmonary bypass

Sepsis SIRS with a presumed or confirmed infectious process

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

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

Infectious Causes Not all patients with infections are febrile. 10% of septic patients are Hypothermic. 35% are normothermic at presentation. Septic patients who fail to develop a temperature have a significantly higher mortality than febrile septic 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? 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? Immunocopromized patient Hemodynamic instability Oliguria Increasing lactate Worsening conscious state Falling platelet counts Worsening coagulopathy.

Intravascular Devices infection and septicemia

Intravascular Devices infection Localized infection Exit site infection Tunnel infection Systemic infection

Catheter-Related Bloodstream Infection Definition A positive catheter culture 15 CFU with concomitant positive blood culture of the same organism. No other identifiable source of infection.

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. Local Catheter-Related Infection Definition

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 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 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 Cultures For cutaneous disinfection: 2% chlorhexidine gluconate 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.

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. Recommendations for Obtaining Blood Cultures

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.

Candidemia 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. Candidemia

Catheter Related Blood Stream Infection Catheter Related Blood Stream Infection CVC 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

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 Catheter Related Blood Stream Infection Catheter Related Blood Stream Infection CVC Maintenance Bundle

Pulmonary Infections and ICU-Acquired Pneumonia

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 Infections Isolation of enterococci, viridans streptococci, coagulase-negative staphylococci, and Candida species 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 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 patients readiness to be weaned from the ventilator.

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 Infection The concentration of urinary bacteria or yeast needed to cause symptomatic urinary tract infection or fever is unclear. Bacteriuria with 10 5 CFUs of bacteria per milliliter of urine during bladder catheterization was associated with a 2.8-fold increase in mortality.

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 Use sterile technique at insertion Perform a daily review of 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

Infectious Diarrhea

C.Difficile associated diarrhea May occur with any antibacterial agent, but the most common causes are clindamycin, cephalosporins, and fluoroquinolones. some patients with C.difficile especially those who are postoperative, may present with ileus or toxic megacolon or leukocytosis without diarrhea.

C.difficileassociated diarrhea SensitivityMethods 40%Stool WBC 75%Lactoferrin latex agg. test 72% 1 st sample 84% 2 nd sample EIA toxin 81% 1 st sample 91% 2 nd sample Tissue Culture assay 71% severe disease 23% mild disease Sigmoidoscopy

C.difficileassociated diarrhea Cultures for C. difficile require 2 to 3 days for growth, and are not specific in distinguishing toxin-positive strains, toxinnegative strains, and asymptomatic carriage. Infection with Klebsiella oxytoca should be considered in patients who are negative for C. difficile. Acute neutropenic enterocolitis or typhlitis should be sought in cancer or stem cell transplant.

Sinusitis

Sinusitis 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.

Sinusitis 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 & Postoperative fever

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 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 Appropriate use of Antibiotics. Appropriate hair removal. Preoperative glucose control in all diabetic patients. Preoperative normothermia.

Postoperative fever 5 Ws Wind (atelectasis/pneumonia) Water (UTI) Walk (DVT-PA) Wound (infection) Wonder (drug reaction)

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 fever

For unknown reasons, most noninfectious disorders usually do not lead to a fever>102F (38.9C). Exceptions: Drug fever Transfusion reaction Neoplasm Malignant hyperthermia Neuroleptic malignant syndrome

Noninfectious causes Acalculous cholecystitis 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 cholecystitis

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 cholecystitis US 90% Specific 100% Sensitive: wall thickness (>3mm) intramural lucencies GB distension pericholecystic fluid intramural sludge Treatment: Nonoperative percutaneous drainage successful 80- 90%. Open cholecystectomy remains treatment of choice. Mortality 15-30%.

Drug-Related Fever

Drug related fever Pathogenesis 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 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 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 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 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. Dantrolene 2 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, and butyrophenones. 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 syndrome Drug-Related Fever Neuroleptic malignant syndrome Risk factors: Dehydration Alcoholism Prior brain injury Use of rapid neuroleptic

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 Drug-Related Fever Neuroleptic malignant syndrome Drug-Related Fever Neuroleptic malignant 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 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 ICU Clinical assessment of new fever should replace automatic, standing-order laboratory and radiologic tests in the ICU. Serum procalcitonin levels and endotoxin activity assay can be employed as an adjunctive diagnostic tool for discriminating infection as the cause for fever or sepsis presentations.

Management of fever In ICU

Dr. Marwan Jabr Alwazzeh Assoc. Prof. of Medicine Consultant Internist/Infectious Diseases...

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