A 63 year old woman was admitted to the Intensive Care Unit 4 days ago following an out of hospital cardiac arrest. She was treated with urgent cardiac angiography and stenting of a significant left main coronary artery lesion.

On moderate sedation, she has started to obey commands  this morning. She is still intubated and ventilated. Currently on an FiO2 of 0.6, she has a PaO2 of 120 mm Hg (16kPa). She has a right internal jugular central line, left radial arterial line, and a right cephalic vein peripheral IV line – all inserted on admission. She is being treated with clopidogrel, ranitidine and intravenous heparin. She has been in atrial fibrillation since admission and this morning she developed a temperature of 38.8°C.

What are the likely causes of fever in this woman?

On examination, she has marked right upper quadrant tenderness and her bilirubin is 100 micromol/L  (N < 17 micromol/L).  What  are the  likely causes  of her abdominal tenderness?

Investigations   do  not  reveal  any  intra-abdominal pathology.  She  continues  to  have fever  and  a septic  screen  is negative.  

List  4 biochemical  (plasma)  markers of sepsis which have been suggested to help differentiate infectious from non-infectious  causes of fever.

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College Answer

What are the likely causes of fever in this woman?

a.   Infectious
•    Chest
•    Line sepsis (peripheral and central lines)
•    Urinary sepsis
•    Sinusitis
•    Angiography site infection

b.  Non-infectious
•    Intra-abdominal conditions
1.  Mesenteric Ischaemia
2.  Acalculous cholecystitis

•    Haematoma secondary to anticoagulation
1. Groin following angiogram
2. Retroperitoneal

•    Pericarditis / Dressler’s (a bit too early)

c.   Drug fever
•    Heparin

On examination, she has marked right upper quadrant tenderness and her bilirubin is
100 micromol/L  (N < 17 micromol/L).  What  are the  likely causes  of her abdominal tenderness?

Possible diagnosis of acalculous cholecystitis

Also consider
1.  right heart failure/ischemic hepatitis
2.  pancreatitis
3.  perforated viscus
4.  calculous cholecystitis

Investigations   do  not  reveal  any  intra-abdominal pathology.  She  continues  to  have fever  and  a septic  screen  is negative.  

List  4 biochemical  (plasma)  markers of sepsis which have been suggested to help differentiate infectious from non-infectious  causes of fever.
1. CRP
2. Procalcitonin
3. Lipopolysaccharide binding protein (LBP)
4. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1)

Discussion

The non-specific differentials for fever are numerous. All the infectious and non-infectious causes of fever are discussed at length in the Required Reading section.

This patient's clues are an out of hospital cardiac arrest, a myocardial infarction, mechnical ventilation, and potentially dodgy lines.

Thus, the differentials can be narrowed:

Infectious causes:

  • Infectious pathology which triggered the arrest (and that could be anything - pneumonia, UTI, cholecystitis, what have you)
  • Aspiration pneumonia
  • Ischaemic bowel with gut translocation
  • Contaminated central line

Non-infectious causes:

  • Global hypoxic-ischamic SIRS
  • Groin haematoma post angiography
  • Retroperitoneal hematoma
  • Drug fever

The raised bilirubin and RUQ tenderness suggests that the candidate should form differentials around a dysfunctional liver or gall bladder; thus:

Other causes of RUQ pain which neglect the raised bilirubin:

  • Pancreatitis
  • Duodenal or gastric ulceration
  • Bowel ischaemia

Biochemical markers of sepsis include:

The whole range of biochemical markers of sepsis, together with their advantages and disadvantages, is discussed at length in the Required Reading section.

 

References

References

Povoa, P., et al. "C-reactive protein as an indicator of sepsis." Intensive care medicine 24.10 (1998): 1052-1056.

Wacker, Christina, et al. "Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis." The Lancet infectious diseases 13.5 (2013): 426-435.

Opal, Steven M., et al. "Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock." Journal of Infectious Diseases 180.5 (1999): 1584-1589.

Shozushima, Tatsuyori, et al. "Usefulness of presepsin (sCD14-ST) measurements as a marker for the diagnosis and severity of sepsis that satisfied diagnostic criteria of systemic inflammatory response syndrome."Journal of Infection and Chemotherapy 17.6 (2011): 764-769.

Gámez‐Díaz, Laura Y., et al. "Diagnostic Accuracy of HMGB‐1, sTREM‐1, and CD64 as Markers of Sepsis in Patients Recently Admitted to the Emergency Department." Academic Emergency Medicine 18.8 (2011): 807-815.

Kwofie, L., et al. "Evaluation of circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to predict risk profile, response to antimicrobial therapy, and development of complications in patients with chemotherapy-associated febrile neutropenia: a pilot study." Annals of hematology 91.4 (2012): 605-611.

Gros, Antoine, et al. "The sensitivity of neutrophil CD64 expression as a biomarker of bacterial infection is low in critically ill patients." Intensive care medicine 38.3 (2012): 445-452.

Gámez‐Díaz, Laura Y., et al. "Diagnostic Accuracy of HMGB‐1, sTREM‐1, and CD64 as Markers of Sepsis in Patients Recently Admitted to the Emergency Department." Academic Emergency Medicine 18.8 (2011): 807-815.

Calfee, Carolyn S., and Jérôme Pugin. "The search for diagnostic markers in sepsis: many miles yet to go." American journal of respiratory and critical care medicine 186.1 (2012): 2-4.