Evalution of New Fever In The Critically Ill Patient - Standard Treatment Guidelines

New onset of fever in Intensive care unit is a very common finding, and triggers a response of various investigations and addition of new antibiotics which may not be needed many times. This leads to increasing cost and adds to increased utilizations of resources. All new fevers in ICU should be evaluated in a prudent and cost effective manner.

Ministry of Health and Family Welfare has come out with the Standard Treatment Guidelines for Evalution of New Fever In The Critically Ill Patient. Following are its major recommendations.

Case Definition

i. In non-immunosuppressed patient two consecutive temperature (core) of more than 101° F warrants further investigation.

ii. In neutropenic patient a single temperature of 101° F should be considered important

iii. New onset of fever below this range, in a hemodynamically stable patient requires a bedside assessment to look for a source of infection and non infectious fever and sending investigation appropriately.

iv. Recording fever

• All patients in ICU should have hourly recording of temperature and recorded in nursing chart.


• Uniformity of scale (Centigrade or Fahrenheit should be maintained)


• The site of temperature recording should be recorded (Oral, axillary, rectal or tympanic)


• Larger ICUs should have access to core temperature (rectal, tympanic or bladder) measurement device


• The instrument should be properly calibrated and sterilized. Thermometers should not be shared between patients to reduce cross infection

Incidence of the condition in our country

30% patients become febrile during hospitalizations. Up to 90% critically ill patients with severe sepsis experience fever during ICU stay. ICU patients will generally present a newly elevated temperature at some point during their stay. Fever in ICU could be infectious, non-infectious or mixed origin and confirmation of source is difficult. A prudent, cost-effective assessment is necessary.

Differential diagnosis: Non-infectious causes of fever

a. CNS: SAH, ICH, Infarction

b. Cardiac: MI, Pericarditis

c. Pulmonary: Atelectasis, PE, fibro-proliferative phase of ARDS

d. Hepatobiliary & GIT: Acalculus cholecystitis, acute pancreatitis, active Crohn’s disease, toxic megacolon, alcoholic hepatitis

e. Rheumatologic syndromes: Vasculitis, SLE, RA, Good pasture's syndrome

f. Endocrine: Hyperthyroidism, adrenal insufficiency, phaeochrocytoma

g. Other miscellaneous non-infectious causes:

i. Drug fever

ii. Transfusion reactions

iii. Neoplasms

iv. Malignant hyperthermia

v. Neuroleptic malignant syndrome

vi. Serotonin syndrome

vii. Opioid withdrawal syndrome

viii. Alcohol withdrawal syndrome

ix. Devitalized tissue secondary to trauma

x. Hematoma

h. Infectious causes of fever

i. CNS: Meningitis, Encephalitis, Brain abscess, Epidural abscess

ii. Head & Neck: Acute suppurative parotitis, Acute sinusitis, ASOM, Para and retropharyngeal abscesses.

iii. CVS: Endocarditis, Catheter related infection

iv. Pulmonary & Mediastinal: Pneumonia, Empyema, Mediastinitis

v. Hepatobiliary & GIT: Appendicitis, Diverticulitis, Peritonitis, Intraperitoneal abscess, Perirectal abscess, Infected pancreatitis, Acute cholecystitis, Cholangitis, Hepatic abscesses, Acute viral hepatitis

vi. Genitourinary: Bacterial or fungal cystitis, Pyelonephritis, Perinephric abscess, Tubo-ovarian mass, Endometritis, Prostatitis

vii. Breast: Mastitis, abscess

viii. Cutaneous: Cellulitis, Suppurative wound infection, Necrotizing fasciitis, Bacterial myositis, Herpes zoster

ix. Osseous: Osteomyelitis

Prevention & Counseling

Staff working in the ICU should be familiar with drug fever and non- infectious causes of fever. Strict asepsis, hand hygiene measures & universal precautions can bring down the infection related fevers. Regular surveillance can help in identifying non-compliant staff, which can be appropriately counseled.

Optimal Diagnostic Criteria, Investigations, treatment & referral criteria

*Situation1: At secondary Hospital/ Non-Metro situations: Optimal standards of treatment in situations where technology & resources are limited.

a. Clinical Diagnosis:

i. Patients are not febrile: euthermic or hypothermic - with life-threatening infection:

1. Elderly

2. Open abdominal wound

3. Large burns

4. Patients on ECMO, CRRT

5. CHF

6. End-stage liver disease, CRF

7. Patients on anti-inflammatory or antipyretic drugs.

ii. Symptoms and signs in the absence of fever, which mandate a comprehensive search for infection and aggressive, immediate empirical therapy: Unexplained hypotension, tachycardia, tachypnea, confusion, rigors, skin lesions, respiratory manifestations, oliguria, lactic acidosis, leukocytosis, leukopenia, immature neutrophils (i.e., bands) of 10%, or thrombocytopenia.

a. Key elements in evaluation: History & physical examination. Look at wounds, surgical incision sites, vascular access and pressure ulcers. Obtain/review Chest Xray, look for new infiltrates or effusions. Appropriate lab studies: Cultures, WBC, PBS. Remove CVC > 96 hrs Send tip for semi quantitative culture.Send stool sample in patients on ABx for> 3 days.C difficile toxin. Diagnostic thoracocentesis, paracentesis, LP, Ultrasound/CT

Initial Assessnent

a. Focused history and bedside review of nursing chart and patients notes should be done. A detailed medication history, line manipulation, blood transfusion, appearance of new rash, diarrhea, or any new procedure performed should be enquired

b. Focused physical examination should be performed looking for any source of sepsis or non-infectious cause of fever.

c. Common infectious causes of new fever in ICU

Hospital acquired or Ventilator associated pneumonia- Intubated for more than 48 hours. New fever, purulent secretion, bronchial breathing

Central line sepsis-Line in place for more than 48 hours Erythema, purulent discharge at central line site.

Urinary catheter related infection – Catheter more than 48 hours in place,suprapubic tenderness cloudy urine

Surgical site infection – purulent discharge from wound site

Sinusitis- Nasogastric or nasotracheal tube, purulent nasal discharge

Parotitis- poor oral hygiene, unilateral tender parotid swelling

A calculus cholecystitis- abdominal tenderness, intolerance of feed

d. Common non infectious causes of fever in ICU

Rash- drugs (antibiotics,antiepileptics, NSAIDSetc.)

Unilateral painful swelling of limb- Deep Venous thrombosis

Thrombophlebitis

Investigation

Investigation to be performed (in all facilities)

a. Total and differential white count

b. Peripheral smear for toxic granules

c. CRP

d. Blood culture – All ICUS should have a protocol for sending blood culture. Recommendation for blood cultures:

• CULTURE NUMBER- Obtain 3 to 4 blood cultures within the first 24 hrs of the onset of fever - first cultures before the initiation of antimicrobial therapy - drawn consecutively or simultaneously, - endovascular infection - separate venipunctures by timed intervals can be drawn to demonstrate continuous bacteremia.


• Additional blood cultures to be drawn only: - clinical suspicion of continuing or recurrent bacteremia or fungemia or-? for test of cure, -48–96 hrs after initiation of appropriate therapy for bacteremia/fungemia.


• Additional cultures should always bepaired.


• For patients- without an indwellingvascular catheter - at least 2 blood cultures using strict aseptic technique from peripheral sites - by separate venipunctures after appropriate disinfection of the skin.


• For cutaneous disinfection, 2% chlorhexidine gluconate in 70% isopropyl alcohol is the preferred skin antiseptic; tincture of iodine is equally effective. Both require -30 secs of drying time before the culture procedure. Povidone iodine is an acceptable alternative; - t must be allowed to dry for 2 mins.

e. Wound swab for gram stain, culture and sensitivity

f. Endotracheal suction for gram stain C & S (semiquantitative)

g. Urine for gram stain C&S (semi-quantitative)

h. Central line tip for C&S

i. Chest x-ray

j. Abdominal USG

k. X-ray sinus

l. Transthoracic echocardiogram Investigation to be performed in tertiary care center.

a. Procalcitonin

b. Chest CT

c. Bronchoscopy with lavage

d. CT sinus

e. CT abdomen for any collection

f. Four sets of blood culture

g. Blood for fungal culture

h. Stool for

c. difficile toxin

e. MIC or e-test of antibiotics

f. Venous Doppler of legs

g. Transesophageal Echocardiogram

Management

It will depend on the underlying cause. Non specific treatment with antipyretic should be instituted in patients with central nervous system disorder, extremes of age, poor cardiac reserve.

Referral Criteria: If higher diagnostic tests and imaging techniques are not available and the patient is not improving, transfer to well equipped centres should be undertaken.

Suggested Reading

1. Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Naomi P. O’Grady, MD; Philip S. Barie, MD, MBA, FCCM; John G. Bartlett et al Crit Care Med 2008; 36:1330–1349

2. Fever in ICU. Paul E Marik. CHEST 2000; 117:855–869

3. Clinical practice guidelines for the diagnosis and management of intravascular catheterrelated infection: 2009 Update by the Infectious Diseases Society of America. Mermel, LA, Allon, M, Bouza, E, et al Clin Infect Dis 2009; 49:1.

4. CDC/NHSN surveillance definition of healthcare-associated infection and criteria for specific types of infections in the acute care setting. Horan, TC, Andrus, M, Dudeck, MA.Am J Infect Control 2008; 36:309.

Guidelines by The Ministry of Health and Family Welfare :

Subhash Todi, Consultant Physician and Intensivist, AMRI Hospital, Kolkata