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Tools for septic shock

Tools for septic shock. Khanna, Critical Connections 2017, SCCM. SOAP II. Multicenter RCT Randomized >800 patients to each: Norepinephrine Dopamine Inclusion criteria = fluid unresponsive shock Septic – 62% Cardiogenic – 17% Hypovolemic – 16%. DeBacker et al. NEJM 2010. VASST.

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Tools for septic shock

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  1. Tools for septic shock

  2. Khanna, Critical Connections 2017, SCCM

  3. SOAP II • Multicenter RCT • Randomized >800 patients to each: • Norepinephrine • Dopamine • Inclusion criteria = fluid unresponsive shock • Septic – 62% • Cardiogenic – 17% • Hypovolemic – 16% DeBacker et al. NEJM 2010

  4. VASST • Multicenter RCT • Randomization (~400 in each): • Vasopressin • Started on 0.03 u/min and titrated to 0.05u/min • Norepinephrine • Started at 5 mcg/min and titrated to 15 mcg/min • Randomized after 12 hours of therapy on average • Patients already on vasopressors • Outcomes: • HR lower in vasopressin group • 90d mortality in “Less severe sepsis” improved with vasopressin (RR=0.78) Russell NEJM 2008

  5. ATHOS-3 • Multicenter RCT • Randomized (150 in each): • Angiotensin II • Dose started at 20 ng/kg/min up to max 300 ng/kg/min • Placebo • Titrated over 3 hours, kept other vasopressors steady • After 3 hours, other vasopressors titrated to goal MAP >65mmHg Khanna NEJM 2017

  6. ATHOS-3 Khanna NEJM 2017

  7. Steroids in Shock • Small studies showing some reduction of vasopressors with steroids • Multicenter RCT, French • Patients refractory to IV fluids, dopamine with low UOP, on ventilator • Enrollment within 8 hours • Randomized (150 in each): • Hydrocortisone 50mg q6hrs + 50mcg fludrocortisone daily x 7 days • Placebo • Divided results based on responders and non-responders • Dose of corticotropin 250mcg • Check at 30, 60 minutes • Increase in cortisol by 9ug/mL or less • Primary outcome - 28d mortality • 53% vs 63% (OR 0.5, p = 0.02) in non-responders • No difference in 1 year mortality • Vasopressors 7 days vs 10 days Annane, NEJM 2002

  8. Steroids in Shock Annane, NEJM 2002

  9. Steroids in Shock • CORTICUS • Some follow up studies suggested increased risk of infection • Enrollment within 72 hours • Less strict inclusion criteria = less sick patients • Randomized (250 in each): • Hydrocortisone x 5 days, taper • Placebo • Responders and non-responders divided the same way • Primary endpoint – 28d mortality • 34% vs 32% (p = 0.51) • No difference in responder/non-responder • Time to reversal of shock: • 3.3d vs 5.8d (p<0.001) • Increased risk of new sepsis or septic shock (OR 1.37) Sprung NEJM 2008

  10. Steroids in Shock Sprung NEJM 2008

  11. Steroids in Shock • ADRENAL • Previously smaller, underpowered trials • Multicenter, international RCT • Inclusion • Ventilator, SIRS, vasopressors • Randomized: (1800 in each) • Hydrocortisone 200mg/d continuous infusion x 7d • Placebo • No ACTH stim testing done • Primary outcome – 90d mortality • 27.9% vs 28.8% (OR 0.95, p=0.5) • Time to shock reversal • 3d vs 4d (HR 1.32, p<0.001) • No increased risk of shock recurrence or new bacteremia • Reduction in time on ventilator Venkatesh, NEJM 2018

  12. Steroids in Shock Venkatesh, NEJM 2018

  13. Vitamin C, Thiamine and Hydrocortisone • Why Vitamin C • Vitamin C is low in sepsis • Vitamin C plays a role in tyrosine hydroxylase function and many other microvascular roles • Tyrosine is an upstream molecule in the synthesis of epinephrine • 47 consecutive patients receiving standard of care • 47 consecutive patients in treatment: • Vitamin C 1500mg IV q6hrs x 4 days • Thiamine 200mg IV q12hrs x 4 days - to prevent kidney stones • Hydrocortisone 50mg IV q6hrs x 7 days • Around 60% patients in the standard of care group were treated with hydrocortisone Marik Chest 2017

  14. Vitamin C, Thiamine and Hydrocortisone Marik Chest 2017

  15. Shock: Tools • Vasopressors • First choice should be norepinephrine • Vasopressin can lower catecholamine dosing • Possibly better in less severe sepsis • Angiotensin II is a promising medication that may be used more in the future • Steroids • Likely no reduction in mortality • Quicker resolution of shock • Vitamin C/Thiamine/Hydrocortisone • Interesting data, no RCT yet • Are you an early adopter?

  16. Objectives: • Identify a patient in shock • Learn the different types of shock and their acute management • With a focus on septic shock, identify best practices • Familiarize yourself with vasopressors and advanced medical therapies

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