Delaney on Sepsis Resuscitation 2012
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Delaney on Sepsis Resuscitation 2012

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Anthony Delaney, an Emergency Physician and Intensivist from Sydney gives an update on Sepsis Resuscitation in 2012. And he doesn't even talk about ARISE!

Anthony Delaney, an Emergency Physician and Intensivist from Sydney gives an update on Sepsis Resuscitation in 2012. And he doesn't even talk about ARISE!

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Delaney on Sepsis Resuscitation 2012 Delaney on Sepsis Resuscitation 2012 Presentation Transcript

  • AN UPDATE ON SEPSISRESUSCITATIONAnthony Delaney MBBS MSc FACEM FCICMStaff Specialist in Intensive Care, Royal North Shore HospitalSenior Lecturer, Sydney Medical School, University of Sydney
  • A Big Topic Activated Protein C? Which Fluid? How much fluid? Resuscitation goals?
  • Drotrecogin alpha (activated) for adultswith septic shock Population:  Adults, sepsis, hypoperfusion (BE <5mmol/L, HCO3<18 mmol/L, lactate >2.5 mmol/L) or renal or liver dysfunction, and noradrenaline ≥5 g/min for 4 hours after 30ml/kg fluid  May 2008 – August 2011 in 208 sites Intervention:  Drotrecogin alpha activated 24mg/kg/hr for 96 hours Comparison:  Placebo Outcome:  Primary outcome: All cause mortality at 28 days
  • Drotrecogin alpha (activated) for adultswith septic shock Allocation concealment:  Centralised randomisation system Blinding:  Placebo controlled Complete follow-up:  Not too bad Intention to treat analysis  yes Baseline balance:  Yes Treated equally apart from intervention:  I think so
  • Drotrecogin alpha (activated) for adultswith septic shock
  • Drotrecogin alpha (activated) for adultswith septic shock Not so much
  • Assessment of haemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study Population:  Adults with severe sepsis Intervention:  Hydroxyethyl starch 130/0.4 (Voluven) Comparison:  0.9% Saline Outcome:  Amount of study drug required to achieve a MAP ≥65mmHg for 4 hours + 2 of  CVP 8-12  u/o >2ml/Kg  ScvO2 ≥70%
  • Assessment of haemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study Allocation concealment:  Not described Blinding:  Yes, same as CHEST Complete follow-up:  Unsure Intention to treat analysis:  Yes, but…. Baseline balance:  Probably, but…. Concomittant treatment:  Not sure,  Steroids and source control not mentioned
  • Assessment of haemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study
  • Assessment of haemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study
  • Assessment of haemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study Excluded 12 in the HES group and 10 in the NaCl group who never achieved haemodynamic stability (?)
  • Assessment of haemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study Mortality 28 days  HES 31/100 (31.0%) v NaCl 24/95 (25.3%)  RR = 1.1 (95% confidence limits 0.70 to 1.72) Mortality 90 days  HES 40/99 (40%) v NaCl 32/95 (34%)  RR = 1.2 (95% confidence limits 0.83 to 1.74) No difference in renal impairment Blood transfusion  HES 29/100 (29.0%) v 20/96 (20.8%)  P=0.25
  • Assessment of haemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study Less HES was used to reach haemodynamic stability compared to saline  1379 ml v 1709 ml  Difference of 300ml  P=0.02 No difference in time to haemodynamic stability “No difference in mortality”???
  • Assessment of haemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study Significantly less volume was required to achieve haemodynamic stability for HES compared to NaCl in patients with severe sepsis No difference in surrogate measures of renal function nor mortality Underpowered trial with methodologic limitations, using surrogate endpoints to draw conclusions
  • Hydroxyethyl starch 130/0.42 versusRinger’s acetate in severe sepsis Population:  ≥18 yo with severe sepsis in the previous 24 hours  SIRS + defined focus of infection + one organ failure Intervention:  Hydroxyethyl starch 130/0.42 Comparison:  Ringers acetate Outcome:  Death or dependence on dialysis at day 90
  • Hydroxyethyl starch 130/0.42 versusRinger’s acetate in severe sepsis Allocation concealment:  Centralised randomisation system Blinding:  Yes  Patients, clinicians, DSMC, Statistician, writing committee Complete follow-up:  Not too bad Intention to treat:  Pretty much Baseline balance:  Yes Treated equally apart from intervention:  I think so
  • Hydroxyethyl starch 130/0.42 versusRinger’s acetate in severe sepsis I think we should probably avoid hydroxyethyl starch 130/0.42 in patients with severe sepsis Await the results of CHEST (Crystalloid versus hydroxy-ethyl starch) with interest  HES 130/0.4!
  • Mortality after fluid bolus in AfricanChildren with severe infection Population:  Children 60 days to 12 years  Kenya, Tanzania and Uganda  Severe febrile illness, reduced LOC, respiratory distress, poor perfusion  Excluded those with severe malnutrition, gastroenteritis, non infectious shock Intervention:  20-40ml/Kg Albumin, 20-40ml/Kg saline, Comparison:  Maintenance fluids only Outcome:  Mortality at 48 hours
  • Mortality after fluid bolus in AfricanChildren with severe infection Intervention (all trial participants):  General paediatric ward  Training to staff in paediatric life support  Basic infrastructure: NIBP and O2 sats  2.5-4.0 ml/Kg/Hr maintenance fluids, antibiotics, antimalarials, glucose, 20ml/Kg blood if Hb <5  Increased sample size due to lower than anticipated overall mortality
  • Mortality after fluid bolus in AfricanChildren with severe infection Allocation concealment:  Opaque sealed numbered envelopes Blinding:  Not really  End-point review committee blinded to treatment allocation Complete follow-up:  Very good considering Intention to treat:  Yes Baseline balance:  Yes Treated equally apart from intervention:  I think so
  • Mortality after fluid bolus in AfricanChildren with severe infection DUDE!! Care with fluid boluses next time you are resuscitating kids with ? Sepsis in Africa Question some dogma
  • Positive fluid balance and elevated CVP in septic shock Retrospective analysis of data from VASST 778 patients Analysis stratified by quartiles using cox proportional hazards models  Age, APACHE II score, dose of noradrenaline
  • Positive fluid balance and elevated CVP in septic shock
  • Positive fluid balance and elevated CVP in septic shock
  • Positive fluid balance and elevated CVP in septic shockIt might just be worthwhilethinking about the dogma thatmore fluid is better for you?
  • Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy Population:  > 17 years old  Severe sepsis or septic shock  BP < 90 after 20ml/Kg fluid OR lactate > 4mmol/L Intervention:  Quantitative resuscitation guided by lactate clearance (10% per hour) Comparison:  Quantitative resuscitation guided by ScvO2 (ScvO2 >70%) Outcome:  In-hospital mortality
  • Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy Allocation concealment:  Opaque sealed envelopes Blinding:  No, …  Subsequent staff were Complete follow-up  Yes Baseline balance:  It appears so Concomitant therapy:  Probably
  • • In- hospital mortality• Estimate of in-hospital mortality 25% in the ScvO2 group• Sample size non-inferiority: 10% boundary, =0.05 (one-sided), =0.71
  • Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy It may be more important to pay attention to ensuring that the patient is resuscitated adequately, rather than the specific goals.
  • QUESTIONS ??