Web site designed and maintained by Chris Cairns © SICS EBM Group 2004
Principal Investigator: Dr Malcolm Daniel
Currently investigating the Evidence Based management of Sepsis
Sepsis – Diagnosis, Prognosis and Treatment
Consultant in Anaesthesia and Intensive Care
Department of Anaesthesia, Walton Building, Glasgow Royal Infirmary, 84 Castle Street, G4 0SF
This review focuses on sepsis. The SCCM / ACCP definition of sepsis is used:
Systemic Inflammatory Response Syndrome (SIRS): Two or more of the following clinical signs of systemic response to endothelial inflammation:
Sepsis: 2 or more SIRS criteria in response to infection.
Severe Sepsis: Sepsis associated with hypotension or organ dysfunction or organ hypoperfusion.
Septic Shock: Sepsis-induced hypotension (systolic blood pressure < 90 mmHg or a reduction ≥ 40mmHg from baseline) despite adequate fluid resuscitation along with signs of hypoperfusion.
We have chosen not to just consider treatments for sepsis, but also, where relevant the usefulness of diagnostic tests and the power of prognostic tests / factors.
We need not only to be able to treat, but also identify when sepsis is present, and accurate prognostic information helps us decide in treatment and in communication with the patient and their family.
Each critically appraised topic (CAT) contains a brief (1 page) summary of the article reviewed. This includes 3 useful features:
Trish Greenhalgh’s BMJ article “How to read a paper: The Medline database” gives further useful details on how do this, together with details of search strategies that can be used.
This collection does not tell you how to manage your patient. We have produced a summary the evidence together with an index of the weight of the evidence, but only you (with your personal clinical expertise), your patient (with their ideas and values), together with knowledge of the practice environment in which you work can determine the correct path.
Activated protein C – One randomised controlled trial. One life saved for every 16 patients treated with activated protein C compared to placebo (95% confidence interval 9 to 44). Uncertain if there is increased risk of bleeding associated with this treatment. The Scottish Intensive Care Society has issued guidelines on use of Recombinant Human Protein C (activated).
Antithrombin III – no evidence of improved survival in sepsis, but evidence of increased risk of bleeding. Further increased risk of bleeding with concomitant use of heparin.
Early goal directed therapy - For every 7 patients with severe sepsis or septic shock treated with early goal-directed therapy (conventional resuscitation targets plus central venous oxygen saturation ≥ 70%), compared to conventional therapy (CVP ≥ 8 – 12 mmHg, MAP ≥ 65 mmHg, urine output ≥ 0.5 ml/kg/h), one less patient dies in hospital (95% confidence interval 4 to 27).
Hydrocortisone –2 small trials showed earlier shock reversal, one of which showed a reduction in mortality, our certainty was limited by the small sample size. Most recent randomized controlled trial showed (> 200 patients), in patients with a low / no response to short synacthen (ACTH) test (increment < 250 nmol.l-1) one life was saved (at hospital discharge) for every 7 patients given hydrocortisone 200 mg/day compared to placebo (95% confidence interval 4 to 27).
Short synacthen test – One cohort study. The baseline cortisol together with the response to a short synacthen test divides patients with sepsis into 3 groups. Patients with a low or no response to synacthen are at a greater risk of death. This was the basis for the threshold used in the study noted above.
Intensive insulin therapy – One randomised controlled trial. For every 29 patients given intensive insulin therapy, to keep glucose 4.4-6.1 mmol.l-1, compared to standard therapy (to keep glucose 10.0 - 11.1 mmol.l-1), one less patient dies in ICU. (95% confidence interval 17 to 101) There was an increased risk of biochemical, but not symptomatic, hypoglycaemia in the intensively treated patients.
Procalcitonin level – One cohort study. This test may help separate those patients with SIRS (no infection) from those with sepsis (infection). Pre-test probability of sepsis syndrome 77%. If the procalcitonin was positive (³ 1.1 ng.ml-1) the probability of sepsis increased to 94% (likelihood ratio 4.35). If the procalcitonin was negative (< 1.1 ng.ml-1) the probability of sepsis reduced to 12% (likelihood ratio 0.04). There are many causes of a raised procalcitonin, one of which is sepsis, however, a low procalcitonin makes sepsis much less likely.
Furthers areas for CATs: There are a number of other topic areas to review in the management of patients with sepsis. This will be done over time. The author is also happy to carry out searches and reviews of areas you need information in. Send questions to the e-mail address listed above.