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Cabrini ed sepsis 2014 (updated 2015)
- 1.
- 2. Sepsis What it is Whatworks What doesn’t What’s next
- 3. Severe Sepsis andSeptic Shock. N Engl J Med. 2013 Aug;369(9):840-51.
- 4.
- 5. Severity More organ systems= more badness ~20% increase in mortality with each failing organ 6 major systems that fail CVS : Resp : Renal : Hepatic : CNS : Haem
- 6. Australian Stats 2000: 35%mortality 2012: 18.4% mortality Sites: 50.3% pulmonary 19.3% intra-abdominal Mortality Related to Severe Sepsis and Septic Shock Among Critically Ill Patient in Australia and New Zealand. JAMA. 2014 Apr;311(13):1308-1316 Adult-population Incidence of Severe Sepsis in Australia and New Zealand Intensive Care Units. Intensive Care Med. 2004 Apr;30(4):589-96.
- 7. Emergency Role We treatthese patients We are sometimes looking after them for longer
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- 9. Antibiotics (+ airway) Broad Culture Avoid delay De-escalate Durationof Hypotension Before Initiation of Effective Antimicrobial Therapy is the Critical Determinant of Survival in Human Septic Shock. CCM 2006 Jun;34(6): 1589-96 one
- 10. Breathing Low tidal volumes Modestfluid resuscitation Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for ALI and the ARDS. N Enlg J Med. 2000; 342:1301-1308. Comparison of Two Fluid-management Strategies in Acute Lung Injury. N Enlg J Med. 2006 Jun;354(24):2564-75. two
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- 13. Circulation Early goal-directed therapy 2001:30.5% vs 46.5% mortality 2014: No difference, lower mortalities (~20-29%) Early Goal-directed Therapy in the Treatment of Severe Sepsis and Septic Shock. N Engl J Med. 2001 Nov;345(19):1368-77 A Randomised Trial of Protocol-based Care for Early Septic Shock. N Engl J Med. 2014 May;370(18):1683-93 Goal-directed Resuscitation for Patients with Early Septic Shock. N Engl J Med. 2014 Oct;371:1496-1506 Trial of Early, Goal-Directed Resuscitation for Septic Shock. N Engl J Med. 2014 Apr;372:1301-1311 three
- 14. CirculationFluid choices Conflicting evidence Toomuch = bad lungs Too little = reliance on vasopressors African experience Crystalloid or colloid No starches Mortality After Fluid Bolus in African Children with Severe Infection. N Engl J Med 2011;364:2483-2495. A Comparison of Albumin and Saline for Fluid Resuscitation in the ICU. N Engl J Med. 2004 May;350(22):2247- 56. Hydroxyethyl Starch 130/0.42 Versus Ringer’s Acetate in Severe Sepsis. N Engl J Med. 2012 Jul;367(2):124- 34. Association of Hydroxyethyl Starch Administration with Mortality and Acute Kidney Injury in Critically Ill Patients Requiring Volume Resuscitation: a Systematic Review and Meta-analysis. JAMA. 2013 Feb;309(7):678-88. three
- 15. Circulation Vasopressor choices Noradrenaline thenmaybe vasopressin Comparison of Dopamine and Norepinephrine in the Treatment of Shock. N Engl J Med. 2010 Mar;362(9):779-89. Vasopressin Versus Norepinephrine Infusion in Patients with Septic Shock. N Engl J Med. 2008 Feb;358(9):877-87. three
- 16. Circulation You can startnoradrenaline peripherally Arms obs Central or Peripheral Catheters for Initial Venous Access of ICU Patient: a RCT. Crit Care Med 2013 Sep;41(9):2108-15. three
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- 18. Drugs Insulin Tight control hasbeen debunked Aim to keep <10mmol/L Intensive Insulin Therapy in Critically Ill Patients. N Engl J Med. 2001 Nov;345(19):1359-67. Intensive Versus Conventional Glucose Control in Critically Ill Patients. N Engl J Med. 2009 Mar;360(13):1283-97. four
- 19. Drugs Corticosteroids Often given whennoradrenaline requirements are high (>20mcg/min) Effect of Treatment with Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients with Septic Shock. JAMA. 2002 Aug;288(7):862-71. Hydrocortisone Therapy for Patients with Septic Shock. N ENGL J Med. 2008 Jan;358(2):111-24. four
- 20. Drugs Activated Protein C Anti-inflammatory Anti-thrombotic Pro-fibrinolytic 2001:24.7% vs 30.8% mortality Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis. N Engl J Med. 2001 Mar;344(10):699-709. four
- 21. Drugs Activated Protein C 2012 Nomortality benefit at 28 or 90 days Drotrecogin Alfa (Activated) in Adults with Septic Shock. N Engl J Med. 2012 May;366(22):2055-64. four
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- 23. Source control Intervene within first12 hours of diagnosis being made The least physiologically insulting intervention Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Crit Care Med. 2013 Feb;41(2):580- 637. five
- 24. Supportive Head-up Sedation and analgesia DVTprophylaxis Stress ulcer prophylaxis Nutrition Care goals six
- 25. Summary We are gettingbetter Recognise early Give fluid but not too much 2014 trilogy of sepsis trials Remember the 20% rule-of-thumb when talking to patient and families Carry a six-pack with you
Editor's Notes
- #4 Pathophysiology is complex Inflammatory and thrombotic pathways Different bugs, different hosts, different response Sites for new therapies - hasn't been born out in evidence yet
- #5 Sepsis - infection + systemic manifestations (SIRS sensitive but not specific) Severe - organ dysfunction Shock - hypotension refractory to fluid resus or high lactate
- #6 CVS - intropes Resp - ventilation Renal - RRT Hepatic - encephalopathy CNS - decreased GCS Haem - DIC
- #7 More patients being discharge home and less discharge to rehabilitation May represent those surviving are surviving better
- #8 We should be able to provide the same ongoing evidence-based care that will be provided in ICU particularly if there is a delay to transfer
- #9 Approach taught in ICU at Cabrini from an approach used at St Paul’s Hospital in Vancouver Encompasses resuscitation and organ support, antibiotic use, surgery, and modification of the host response to infection
- #10 7.6% increase in mortality with each hour delay. Retrospective cohort . 2731 septic shock patients. Cultures - at least two; different sites; timing doesn't matter, >5mL per bottle Useful in the undifferentiated patient versus the well pneumonia or cellulitis Within 30 mins otherwise give ABs Review results to narrow spectrum
- #11 Low tidal volumes has been well established. May have to tolerate a degree of resp acidosis. May need more PEEP also. 861 patients in initial study - no mortality benefit but less time ventilated and in ICU. Later small studies show a 28-day mortality benefit
- #12 Getting to the crux here with approaches to the shocked / hyperlactataemic patients
- #13 Titrate our fluid and vasopressor management Traditional end-points may not reflect ongoing cellular level sepsis - lactate levels, oxygen delivery and consumption
- #14 Can early recognition and protocolised aggressive treatment of severe sepsis and septic shock in the ED (bringing the ICU level-of-care to ED). Early recognition yes. Overly protocolised no? Rivers study in 2001 show a huge mortality benefit to this approach but was a small study (only 263). High mortality in usual treatment arm compared to Aus stats. PROCESS trial found no difference. 3 groups. Larger numbers (1341). Mortality more closely matches Australia. ARISE (2014). Control vs EGDT. 1600 patients. No difference PROMISE. Control vs EGDT. 1260 patients. Higher mortality rates compared to ARISE and PROCESS
- #15 Too much increases ARDS and ventilation hours, but… …Rivers trial in the treatment group got more fluid and had a lower mortality, but… FEAST showed harm with fluid boluses - stopped early (3000 patient). 7.3% vs 10.5% mortality at 48 hours. SAFE trial (7000 patients) no difference in mortality - possible trend toward benefit in sepsis Hydroxyethyl starches increase mortality and need for RRT
- #16 Many studies. Nothing really conclusive. 2010 NEJM article 1679 shock patients (1044 septic) shows no mortality benefit between noradrenaline and dopamine but many more arrhythmias (AF) with dopamine. Use vasopressin as a noradrenaline sparing agent in refractory shock
- #17 19 out of 128 patient receiving peripheral noradrenaline had extravasation - all which was treated conservatively
- #18 Now looking at cell-level therapies to modify the host response
- #19 Initial trial was surgical only ICU patients - 1548 patients with 4.6% versus 8% mortality. Then a number of trials with smaller numbers and conflicting results NICE SUGAR enrolled 3000 patients expected to have a 3 day ICU stay. Increased mortality 27.5% vs 24.9% and more hypoglycaemia (6.8% vs 0.5%)
- #20 Larger early study indicated mortality benefit in patients with proven relative adrenal insufficiency. 300 septic shock patients. 55% vs 61% Subsequent Cochrane review confirmed this but had not included the largest study (499 patients) which showed no survival benefit however there was earlier reversal of shock
- #21 The first sepsis-specific drug 1690 patients. Trend towards more bleeding in treatment group. Changes made during the study to placebo group, the treatment administered, and the type of patients recruited. Later studies stopped early due to possible harm.
- #22 Lots of ongoing questions about the efficacy and safety of APC given it’s cost and the flaws of the initial study. PROWESS-SHOCK trial show no benefit, inducing in those with APC deficiency, plus an increased rate of bleeding
- #25 Decreased aspiration risk and HAP Ensure patient comfort but minimise over sedation Clexane and stockings unless renal/bleeding/imminent surgery Start feeding within 48 hours - low calorie