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Dr : Rabie Fahmy Zahran. Tropical M. Consultant. Damietta Fever Hospital. Egypt. Introduction : Fever is a common problem in the ICU. Could be due to infectious and non-infectious causes. Objective is to review causes and how to deal with fever in ICU patients. Introduction What is fever? : Fever is a coordinated neuro -endocrinal, autonomic and behavioral response to immune stimulus or tissue injury. Coordinated by the hypothalamus : Neural input from peripheral thermo-receptors. Humeral cues from inflammation or infection. What is fever? Pathophysiology : Pathophysiology Stimulus Leukocyte activation Cytokine (IL-1, IL-6, TNF) Hypothalamus reset thermoregulatory point Heat production Fever .Exogenous pyrogens. •Endotoxin. •Staphylococcal toxin. .viruses. Benefits of fever : Enhances parameters of immune function. Improves antibody production. Activates T-cells. Produces cytokines. Enhances neutrophils ¯ophage function. Benefits of fever How to measure temperature in critically ill patient? : How to measure temperature in critically ill patient? Measurement of temperature : Peripheral temperature measurements: Considered unreliable as influenced by environmental temperatures, mouth breathing etc. Measured in the outer 1.6 mm of skin or mucus membranes. Examples – oral temperature, axillary, skin temperature . Measurement of temperature Measurement of temperature : Core temperature measurements: Not influenced by external factors. More accurately reflects temperature in the internal organs. Examples – pulmonary, rectal, esophageal, tympanic. Measurement of temperature Measurement of temperature : Optimal site Pulmonary – but invasive, requires placement of a pulmonary artery catheter. Alternatives Tympanic – easy but not so accurate. Rectal – uncomfortable. Esophageal requires placement of esophageal probe. Measurement of temperature When we say “fever” in the ICU patient? : When we say “fever” in the ICU patient? What is normal? : Normal body temperature : 36.8OC ( 98.2O F ) Diurnal variations of temperature with evening rise up to 37.8O C (100O F ) What is normal? So when we get worried in the ICU? : Society of Critical Care Medicine (SCCM) and Infectious diseases society of America recommend investigations in the ICU patient if his temperature is above : 38.3OC (101O F ). So when we get worried in the ICU? Approach to fever in the ICU patient : Approach to fever in the ICU patient Approach to fever in ICU : What are the causes of fever in ICU? How do I act when I see a temperature spike ? What investigations to be done ? How I treat fever ? Approach to fever in ICU Approach to fever : Patient who come in with a febrile illness Approach to fever Patient develops fever in ICU What is the cause Of this fever? Cause of fever need to be ascertained Patient presenting to ICU with fever : Patient with an obvious focus of infection Where is the focus ? Patient presenting to ICU with fever Acute un-differentiated fever What is causing this fever ? The obvious focus : Community acquired pneumonia. Acute CNS infection. Urinary tract infection. Abdominal focus of infection. Wound infection / Pus collections. Trauma with infection. The obvious focus The obvious focus : why they admitted to ICU ? Ventilator support : respiratory failure – pneumonia . Hemodynamic support : shock . Renal replacement therapy : renal failure, severe acidosis . Monitoring : Neurological & Hematological dysfunction. The obvious focus Approach to fever : Patients presenting with a febrile illness Approach to fever Patient developing fever in the ICU Is there a focus of infection? Acute undifferentiated fever √ Acute undifferentiated fever : Where no specific focus identified. Look for specific clues to guide in the diagnosis . Acute undifferentiated fever Acute undifferentiated fever : Fever with thrombocytopenia . Fever with hepato - renal dysfunction. Fever with pulmonary renal syndrome. Fever with altered sensorium . Acute undifferentiated fever Acute undifferentiated fever : Fever with thrombocytopenia : Malaria (notably falciparum ) Dengue . Leptospirosis(Weil's disease) . Rickettsial infections . Viral infections. Acute undifferentiated fever Slide 23: Blood smear of Plasmodium falciparum (gametocytes - sexual forms) Slide 24: acute hemorrhagic fever caused by the dengue virus and transmitted by mosquitoes Aedes aegypti. Dengue Slide 25: Leptospirosis Slide 26: Leptospirosis icteric (10% of cases) or anicteric (less severe; 90% of cases).IP : 7-12 days, with fever (biphasic) and "flu-like" illness. + intense headaches, severe myalgia, abdominal pain, nausea, diarrhea, and sometimes rash, conjunctivitis and Conjunctival hemorrhage. "Weil's disease" (icteric form) *This is the name for the classic hepatic and renal form of Leptospirosis in humans, *Signs include: = petechiae = hepatomegaly and jaundice ALT/AST levels rarely exceed 100-200 u. renal tubular damage >>> renal insufficiency The renal insufficiency follows renal tubular damage due to hypoxia or a direct toxic effect of the leptospires. Slide 27: Laboratory studies (Weil disease) * mild thrombocytopenia (as many as 50%), which is often accompanied by renal failure. *Azotemia and renal failure are other prominent characteristics. *Marked Leucocytosis (3,000-26,000 x 109/L). *Prothrombin times may be elevated. *Creatine phosphokinase (CPK) levels are elevated in as many as 50% of patients; acutely, jaundice in Weil disease is associated with very high CPK level, but transaminases are only modestly elevated. Leptospirosis Acute undifferentiated fever : Fever with hepato-renal dysfunction : Malaria (falciparum) . Leptospirosis. Scrub typhus(transmitted by some species of mites ) . Fulminant hepatic failure with hepato-renal . Acute undifferentiated fever Slide 29: Humans acquire the disease when infected chiggers bite them and transmit O. tsutsugamushi. Scrub Typhus Symptoms Bacteria multiply at the inoculation site and frequently form a papule that ulcerates & becomes necrotic. This pathognomonic focal lesion is called an eschar. Regional lymphadenopathy develops & progresses to generalized lymphadenopathy in a few days. In the severe cases, it can lead to :-Pneumonia with adult respiratory distress syndrome :-Circulatory failure resulting in death. Eschar = Clinical Sign of Scrub Typhus Mortality rates in untreated patients normally range from 0-30% but rates as high as 60% have been reported. Significant morbidity and mortality can be prevented in patients who receive timely, appropriate treatment with antibiotic drugs. Acute undifferentiated fever : Fever with pulmonary-renal dysfunction : Malaria ( falciparum ). Leptospirosis . Scrub typhus . Hantavirus infection . Severe legionella / pneumococcal pneumonia . Acute undifferentiated fever Slide 31: Hantavirus has an IP. of 2–4 weeks in humans. These symptoms can be split into five phases: Febrile phase: 3–7 days fever, chills, sweaty palms, diarrhea, malaise, headaches, nausea, abdominal and back pain, respiratory distress. Hypotensive phase: 2 days :This occurs when the blood platelet levels drop and symptoms can lead to tachycardia and hypoxemia. Oliguric phase: This phase lasts for 3–7 days and is characterized by the onset of renal failure and proteinuria occurs. Diuretic phase: This is characterized by diuresis of 3–6L per day, which can last for a couple of days up to weeks. Convalescent phase: This is normally when recovery occurs and symptoms begin to improve. Acute undifferentiated fever : Fever with altered sensorium : Malaria (cerebral malaria ) . Encephalitis . Meningitis . Typhoid fever . Septic encephalopathy . Brain abscess. Acute undifferentiated fever Approach to fever : Patients presenting with a febrile illness Approach to fever Patient developing fever in the ICU Is there a focus of infection? Acute undifferentiated fever √ √ Patient developing fever in the ICU : Infectious causes Where is the focus? Patient developing fever in the ICU Non-infective causes What is the cause of this fever? Slide 35: Infectious causes Infectious causes of fever whilst in ICU : Ventilator associated pneumonia . Catheter related blood stream infections Uro-sepsis . Intra-abdominal infections . Sinus infections . Infectious Diarrhea . Infectious causes of fever whilst in ICU Infectious causes of fever whilst in ICU : Fungal infections including candidemia . Surgical wound infections . Acalculous cholecystitis . Endocarditis . Meningitis . Infectious causes of fever whilst in ICU Ventilator associated pneumonia . : Ventilator associated pneumonia . Almost all cases occur in mechanically ventilated patients. Signs are: Fever. Leucocytosis. purulent tracheal secretions. new or worsening infiltrates on CXR. Slide 39: However, none of these signs are predictive of pneumonia; Ventilator associated pneumonia remains a clinical diagnosis. Can be confused with fibro-proliferative phase of ARDS, usually accompanied by low-grade fever. Semi-quantitative BAL and protected-brush specimen may be helpful, but not widely available. Ventilator associated pneumonia . Sinusitis : Sinusitis Para-nasal sinusitis accounts for about 5% of nosocomial ICU infections. Bacteriology differs markedly from community-acquired disease. Gram-negative bacilli cause most cases in intubated patients. Polymicrobial infection in up to 50% of cases, reflecting ICU flora. Sinusitis: : Sinusitis: Fever and Leucocytosis often present. Purulent nasal discharge often lacking. Common in trauma and neuro-surgical units. Sinusitis: : Risk factors: Naso-tracheal tubes. -Naso-gastric tubes. nasal packing. -facial fractures. steroid therapy. Diagnosis made easier with sinus CT, which is more sensitive than plain films. Avoid prolonged naso-tracheal intubation. Sinusitis: Slide 43: Non-infectious causes Non-infectious causes of fever in ICU : Non-infectious causes of fever in ICU Drug Fever Drug fever : Drug fever Common offenders Amphotericin B. Cephalosporins . Penicillins Phenytoin Procainamide Quinidine Occasional offenders Cimentidine Carbamazepine Hydralazine Rifampin Streptokinase Vancomycin Non Infectious Causes : Slide 46: Pathogenesis of Drug related fever • 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. Slide 47: Drug fever ( CLINICALLY ): • Unexplained high spiking temperatures and shaking chills. • Usually in 2nd week of drug administration • May be associated with Leucocytosis and eosinophilia. • Relative Bradycardia . • Associated skin rash. • Rapid resolution of fever <72 hrs (if no rash), may take up to 7 days. Summary of approach to fever in ICU : Patients presenting with a febrile illness Summary of approach to fever in ICU Patient developing fever in the ICU Is there a focus of infection? Acute undifferentiated fever Infective Causes Non-infective Causes Approach to fever in ICU : What are the causes of fever in ICU √ How I act when I see a temperature spike? Approach to fever in ICU How I act when there is a temperature spike? : How I act when there is a temperature spike? One temperature spike : One temperature spike Should I be worried? YES In an immunocopromized patient If hemodynamic instability Oliguria. Increasing lactate Worsening conscious state Falling platelet counts Worsening coagulopathy. NO. Small spike No hemodynamic instability Carefully examine clinically for an obvious focus of infection What investigations should be done ? : What investigations should be done ? What investigations should be done ? : Blood count. Imaging – CXR, Scans as indicated (abdomen, sinuses, CT brain , Doppler study) Cultures as appropriate : Urine, Blood cultures (peripheral and through lines), cultures from pus, wound etc, Stool for clostridium What investigations should be done ? What investigations should be done ? : Assess if lines are “old” and if there is any evidence of line sepsis - re-site line if indicated . Change urinary catheter. May need NG tube change – if sinus infection suspected . What investigations should be done ? What investigations should be done ? : Do not forget non-infectious causes: Acute Lung injury/ARDS, Aspiration Deep venous thrombosis, thrombophlebitis Drug fever Decubitus ulceration What investigations should be done ? Acute Respiratory Distress Syndrome : Acute Respiratory Distress Syndrome 1994 AECC. (Aberdeen Exhibition &Conference Centre) Definition: _ Acute onset of respiratory failure. Bilateral chest infiltrates. PAWP 18 mmHg(pulmonary artery wedge pressure ) PaO2/FiO2 < 200 ARDS PaO2/FiO2 < 300 Acute lung injury. (partial pressure of oxygen in arterial blood / fraction of inspired oxygen ) Conditions Associated with ARDS : Conditions Associated with ARDS Direct lung injury Pneumonia Aspiration of gastric contents Pulmonary contusion Fat emboli Inhalation injury Near-drowning Reperfusion pulmonary edema Indirect lung injury Sepsis Multiple trauma Multiple blood transfusions Cardiopulmonary bypass Burns Acute pancreatitis Drug overdose Pathogenesis : Pathogenesis Insult Neutrophil activation Cytokine Inflammation Epithelial and endothelial damage Increased permeability Exudation into alveolar space Recover Fibrosis Cause of fever in ARDS patient : Cause of fever in ARDS patient In 35 ARDS patient: 26(75%) were infectious in origin 9(25%) were noninfectious in origin 5 were due to fibro-proliferation of lung How I treat this fever ? : How I treat this fever ? How I treat? : According to the cause When to administer or change antibiotics? How I treat? How I treat? : When to administer or change antibiotics? Generally in an unstable patient – choose to treat with broad spectrum antibiotics and pull back depending on cultures & clinical response How I treat? Slide 64: Thank you You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.