Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% •...

66
Dr Mai Nguyen CSTEM 3 MMUH 21/8/2015

Transcript of Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% •...

Page 1: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Dr  Mai  Nguyen  

CSTEM  3  MMUH  21/8/2015  

Page 2: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Introduction  •  Common  –  20%  of  ED  referrals  •  Time-­‐dependent  medical  emergency  

•  Body’s  response  to  an  infec=on  injures  its  own  =ssues  and  organs  

Sepsis  !  Shock  !  Mul=ple  organ  failure  !  DEATH  

Page 3: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Epidemiology  •  World-­‐wide—1.8  million  cases  annually    •  300  cases  per  100,000  popula=on/annum  •  MI—208,  stroke—223    

•  Europe—90.4  cases  per  100  000  

•  UK—more  than  100,000  /  year,  death  in  37,000    

•  Mortality  as  high  as  MI  in  the  1960s  •  Ranges  from  15-­‐37%  

•  9th  leading  cause  of  disease-­‐related  deaths  

Page 4: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Economic  Impact  •  Most  expensive  condi=on  treated  in  the  USA  •  $20  billion  in  2011  

•  UK—£  2.5  billion  per  year    •  Average  cost  of  care  £20,000/pa=ent  

•  Ireland–  20,000  €/pa=ent  

Page 5: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Ireland  –  2013  •  60%  of  all  hospital  deaths  had  a  sepsis  or  infec=on  diagnosis  •  16%  of  all  hospital  deaths  designated  with  sepsis  specific  ICD-­‐10-­‐AM  diagnosis  code  

•  Total  number  of  cases  –  8,831  

•  Total  of  hospital  days  –  221,342  •  ALOS  –26  days  (vs  without  infec=on  5.59)  

•  Mortality  28.8%  (31.3%  in  2012,  32.4%  in  2011)  

Page 6: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Prevalence/Sources  •  IMPRESS  trial  –Europe,  US  and  Asia  

Source   Prevalence  

Respiratory   35%  

Urinary   21%  

Intra-­‐abdominal   16.5%  

Catheter-­‐related  BSI   2.3%  

Device-­‐related   1.3%  

CNS   0.8%  

Others  ie  celluli=s,  joints   11.3%  

Page 7: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Health  Impact  •  Sepsis  remains  the  primary  cause  of  death  from  infec=on  •  A  decade  ago  !  37-­‐53%  mortality  

•  Predicted  to  grow  at  rate  of  1.5%  annually    •  Aging  popula=on  •  Increased  number  of  invasive  procedures  

•  Increasing  number  of  people  living  with  co-­‐morbidi=es  

•  Long  term  immuno-­‐suppressive  agents  

Page 8: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Health  Impact  •  Sepsis  guidelines  to  promote  early  recogni=on,  resuscita=on,  and  =mely  referral  to  cri=cal  care  have  led  to  reduc=ons  in  mortality  to  20-­‐30%  

•  Reduced  ICU  admissions  

•  Reduced  ICU  length  of  stay  •  Reduced  hospital  length  of  stay  

•  Following  basic  principles  of  sepsis  management  can  save    £  4000  or  €4,  500  per  pa=ent  

Page 9: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Gaps  •  Lack  of  =mely  history  and  examina=on  (including  adequate  nurse  triage)  on  presenta=on  

•  Lack  of  necessary  inves=ga=ons  •  Failure  to  recognise  the  severity  of  the  illness  •  Inadequate  first-­‐line  treatment  with  fluids  and  an=bio=cs  

•  Delays  in  administering  first-­‐line  treatment  

•  Inadequate  physiological  monitoring  of  vital  signs  •  Delay  in  source  control  of  infec=on  •  Delay  in  senior  medical  input,  and  the  lack  of  =mely  referral  to  cri=cal  care  

Page 10: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Surviving  Sepsis  Campaign  •  Ini=ated  over  a  decade  ago  •  Clear  diagnos=c  and  treatment  protocols  

•  Campaign  has  succeeded  in  reducing  mortality  by  25%  

•  Mortality  increases  by  7.6%  for  each  hour  delay  in  receiving  appropriate  an=bio=cs  

•  In  Ireland  •  33  recommenda=ons,  23  interven=ons  

•  Best-­‐prac=ce,  best-­‐evidence  

Page 11: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 12: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

DeBinitions  •  Systemic  Inflammatory  Response  Syndrome  (SIRS)  

•  Sepsis  =  presence  of  both  infec=on  and  SIRS  •  Severe  Sepsis  =  sepsis  complicated  by  organ  dysfunc=on/failure  

•  SepIc  Shock  =  severe  sepsis  with  circulatory  shock  with  signs  of  organ  dysfunc=on  or  hypo-­‐perfusion  •  Persistent  SBP  <90mmHg,  MAP  <65mmHG,  decrease  by  40mmHG  from  baseline  and  or  lactate  >4  mmol  

Temp:  >38.0  or  <36.0  C  RR:  >20/min  or  PaCO2  <32mmHg  HR:  >90/min  WCC:  <4  or  >12  x  109/L  

Page 13: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 14: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Compliance  reduces  rela=ve  risk  of  death  by  46.6%  

Page 15: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 16: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Management  •  Early  Recogni=on  •  MTS  or  deteriora=ng  pa=ent  •  SIRS  Criteria  •  Senior  advice  •  Transfer    

•  Manage  ABCs  and  Disability  •  Maintain  s02  >  90%  •  2  Large  bore  IVCs  –  VBG/ABG,  FBC,  CRP,  coag,  LFTs,  U&E,  bone,  G&H  

•  Blood  cultures  –  before  Abx  admin,  separate  sites  •  IVF  resuscita=on    

***  Ongoing  re-­‐assessment***  

Page 17: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Management  •  IV  Abx  appropriate  for  suspected/confirmed  infec=on    •  Urgent  Inves=ga=ons  (pending  presenta=on)  •  CXR  •  ECG  •  Urinalysis  

•  Catheterize  if  unwell,  or  for  accurate  ins  and  outs  

Page 18: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Management  •  Is  pa=ent  hypotensive  arer  ini=al  fluid  bolus?  •  Consider  further  250ml-­‐1L  boluses  •  30ml/kg  boluses  

•  Consider  need  for:    •  Central  venous  access  •  Arterial  line  •  Noradrenalin  infusion  

•  Goals  of  Therapy  •  CVP  8-­‐12mmHg  •  MAP  >65mmHg  •  Urinary  output  >0.5ml/kg/hr  •  Scv02  >70%  •  Normalize  lactate  •  Aim  Hb  7-­‐9  g/dl  

Page 19: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Further  Management  •  Urgent  Referral  to  specialty    •  Urgent  CT  -­‐  ?intra-­‐abdominal  sepsis,  ?necro=zing  fascii=s  

•  LMWH  for  thrombo-­‐prophylaxis  

•  IV  PPI  –  reduce  stress-­‐ulcers  

Page 20: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Recommendations  •  IVF  ResuscitaIon  (during  first  6  hours):    •  AIM:  SBP  >  90mmHg  or  MAP  >  65mmHg  OR  

•  CVP    8–12  mm  Hg  

•  MAP  ≥  65  mm  Hg  

•  Urine  output  ≥  0.5  mL/kg/hr  

•  Central  venous    or  mixed  venous  oxygen  satura=on  70%  or  65%,  respec=vely  

•  Isotonic  crystalloids  as  the  ini=al  fluid  of  choice  (30ml/kg)  

•  Albumin  suggested  when  pa=ents  require  substan=al  amounts  of  crystalloids  and  a  colloid  is  being  considered  

Page 21: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 22: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 23: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 24: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

What  about  the  Tricky  Patients?  •  CCF  •  Dialysis  •  Pre-­‐eclampsia  and  sepsis  

•  Same  principles  –bolus  +  review  

•  Use  smaller    volumes  more  oren  

•  Senior/specialty  advice  

Page 25: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Recommendation    •  Empirical  IV  Abx  AdministraIon  •  Should  occur  within  the  first  hour  of  recogniIon  of  sep=c  shock  and  severe  sepsis  

•  Approved  local  guidelines  •  AnIviral  therapy  is  suggested  to  be  ini=ated  as  early  as  possible  in  pa=ents  with  suspected  viral  origin  

START  SMART  9-­‐Fold  increase  in  mortality  with  inappropriate  an=bio=c  choice  

THEN  FOCUS  

Page 26: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 27: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 28: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Recommendations  •  Vasopressor  therapy,  if  required  should  ini=ally  target  MAP  of  65  mmHg  •  Arterial  line  should  be  placed  •  Noradrenaline  as  first  line  

•  Adrenaline  when  addi=onal  agent  is  needed  •  Vasopressin  0.03  units/min  can  be  added  to  NA  

•  Low  dose  dopamine  should  not  be  used  for  renal  protec=on  

Page 29: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Recommendations  •  CorIcosteroids  should  NOT  be  administered  in  the  absence  of  shock  or  if  adequate  fluid  resuscita=on  and  vasopressor  therapy  are  able  to  restore  haemodynamic  stability  •  IV  hydrocor=sone  200mg  /day  if  above  not  achievable  

•  Steroids  should  be  tapered  when  vasopressors  no  longer  required  •  Red  blood  cell  transfusion  recommended  when  Hb  <7.0g/dl  to  target  of  7.0-­‐9.0  g/dl  and  once  =ssue  hypoperfusion  has  resolved  

•  Platelets  administered  prophylac=cally  if  <10,000  mm3  in  absence  of  apparent  bleeding  

•  EPO,  IVIg,  an=-­‐thrombin  and  FFP  not  recommended  

Page 30: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Early  Goal  Directed  Therapy  

Page 31: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

EGDT  •  Principles  of  Goal  directed  therapy  has  long  been  used  for  severe  sepsis  and  sep=c  shock  in  the  ICU  sevng  

                         EARLY  !    Emergency  Department  

•  Has  been  endorsed  in  the  guidelines  of  the  Surviving  Sepsis  Campaign  

•  Key  strategy  to  decrease  mortality  among  pa=ent  presen=ng  to  the  ED  with  sep=c  shock  

•  Involves  adjustments  of  cardiac  preload,  arerload,  and  contrac=lity  to  balance  O2  delivery  with  O2  demand  

Page 32: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

EGDT  in  the  Treatment  of  Severe  Sepsis  and  Septic  Shock,  NEJM  2001,  Rivers  et  al.    •  Urban  ED  (Detroit),  n=  263  •  6  hours  of  early  goal-­‐directed  therapy,  vs  Standard  therapy  (control)  

•  Ini=al  6  hours"  EGDT  –significantly  more  fluid,  red  cell  transfusion  and  inotropic  support  •  Incidence  of  death  due  to  sudden  cardiovascular  collapse  was  double  in  the  standard  therapy  group  

•  In  hospital  mortality:  30.5%  vs  46.5%  (p=0.009)  

•  Interven=on  at  the  earliest  stages  of  severe  sepsis  and  sep=c  shock  has  significant  impact  on  mortality  

Page 33: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 34: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

ProCESS  Trial–  NEJM,  Feb  2014  •  31  EDs  in  the  USA  –  2008-­‐2013,  n=1341  •  EGDT  vs  simplified  quan=ta=ve  resus  vs  usual  care  

•  Pre-­‐randomiza=on  "  30ml/kg  

•  CVCs  placed  in  93.2%  EGDT,  56.5%  of  protocol  group  and  57.9%  of  usual  care  group  

•  IVF  Resuscita=on:  2.8L  vs  3.3  L  vs  2.3  L  •  Vasopressors:  54.9%  vs  52.2%  vs  44.1%  •  Inotropes—Dobutamine:  8.0%  vs  1.1%  vs  0.9%  

•  Blood  transfusions:  14.4%  vs  8.3%  vs  7.5%  

Page 35: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

ProCESS  •  EGDT:  92  deaths  –  21.0%  •  Protocol  based,  std  therapy:  81  deaths  =18.2%  •  Usual  care:  86  deaths  =18.9%  

•  There  were  no  sign  differences  in  90  day  mortality,  1  year  mortality,  LOS  in  ICU  or  hospital,  CV  failure,  respiratory  failure  or  discharge  disposi=on  

•  Two  protocol  based  approaches  !  higher  requirement  for  ICU  and  renal  replacement  therapy  

•  EGDT  required  more  dobutamine  and  gave  more  transfusion  =  €€€  

Page 36: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

ARISE  Trial  –  NEJM,  Sept  2014  •  51  centers  across  Australia  and  New  Zealand,  n=1600  •  EGDT  vs  Standard  care—guided  by  the  trea=ng  clinical  team  (ScvO2  measurements  were  not  permiyed  during  ini=al  6  hours)  

•  Pre-­‐randomiza=on  !  34ml/kg  

•  IVF  in  first  6  hrs:  1964+/-­‐1415ml  vs  1713+/-­‐1401ml  (2.9  vs  2.7)  •  Vasopressor  infusions:  66.6%  vs  57.8%  •  Red  cell  transfusions:  13.6%  vs  7.0%  •  Dobutamine:  15.4%  vs  2.6%  

•  90-­‐day  Mortality:  18.6  vs  18.8%  •  No  significant  difference  in  survival  =me,  in-­‐hospital  mortality,  dura=on  of  organ  support  or  length  of  hospital  stay    

Page 37: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Conclusion  •  EGDT  developed  and  introduced  into  the  ED  sevng  by  Manny  Rivers  has  many  merits  

•  Pa=ents  who  are  iden=fied  early  in  the  ED  as  having  sep=c  shock,  who  receive  =mely  an=bio=cs  and  other  non-­‐resuscita=on  aspects  of  care  promptly,  there  is  no  significant  advantage  of  protocol-­‐based  resuscita=on  over  usual  care    

•  No  significant  benefit  of  the  mandated  use  of  central  venous  catheteriza=on  and  central  hemodynamic  monitoring  in  all  pa=ents.  

Page 38: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Summary  •  Sepsis  6  is  the  minimum  interven=on  •  Sepsis  is  a  con=nuum  

•  Source  control  with  early  IV  Abx  •  IVF  resuscita=on  depending  on  haemodynamic  response    

Page 39: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 40: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 41: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 42: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Early  Goal-­‐directed  Therapy  in  the  Treatment  of  Severe  Sepsis  and  Septic  Shock  

NEJM  2001  

Rivers  et  al.  

Page 43: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Methods  •  Urban  emergency  department  (Detroit)  •  Randomly  assigned  pa=ents  with  severe  sepsis  or  sep=c  shock  to  receiver  either  •  6  hours  of  early  goal-­‐directed  therapy,  vs  •  Standard  therapy  (control)  

•  Clinicians  who  subsequently  assumed  care  were  blinded  to  treatment  assignment  

•  Primary  efficacy  outcome:  in-­‐hospital  mortality  

•  End  points=  APACHE  II  score    (obtained  at  72  hours)  

Page 44: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Results    •  263  enrolled  pa=ents  •  EGDT=  130  •  Standard  therapy=133  •  No  significant  differences  between  group  

•  In  hospital  mortality  •  EGDT=  30.5%  •  Standard  therapy  =  46.5%  (p=0.009)  

Page 45: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Results:  EGDT  vs  Standard  •  Higher  MAP,  lower  HR  •  Goals  for  CVP,  MAP  and  UO  were  met  in  99.2%  vs  86.1%  

•  Higher  mean  in  central  venous  O2  sat  –70.4  vs  65.3%  

•  Lower  lactate  concentra=on—3.0  vs  3.9  •  Lower  base  deficit—2.0  vs  5.1  

•  Higher  pH—7.4  vs  7.36  

•  Mean  APACHE  II  score  significantly  lower  

**P  <  or  =  0.02  for  all  comparisons  

Page 46: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 47: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Discussion  •  Ini=al  6  hours  •  EGDT  !  received  significantly  more  fluid,  red  cell  transfusion  and  inotropic  support  

•  Incidence  of  death  due  to  sudden  cardiovascular  collapse  was  double  in  the  standard  therapy  group  •  Suggests  than  an  abrupt  transi=on  to  severe  disease  (2nd  to  haemodynamic  compromise)    is  important  cause  of  death  

Page 48: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Conclusion  •  EGDT  provides  significant  benefits  with  respect  to  outcome  in  pa=ents  with  severe  sepsis  and  sep=c  shock  in  the  ED  sevng  

•  Interven=on  at  the  earliest  stages  of  severe  sepsis  and  sep=c  shock  has  significant  impact  on  mortality  

Page 49: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

A  Randomised  Trial  of  Protocol-­‐Based  Care  for  Early  Septic  Shock  ProCESS  Trial    NEJM  2014  

Yealy  et  al  

Page 50: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Methods  •  31  Emergency  Departments  in  the  United  States  •  March  2008-­‐May  2013  

•  Randomly  assigned  pa=ents  with  sep=c  shock  to  one  of  three  groups  •  Protocol  based  EGDT  •  Protocol  based  standard  therapy  –less  aggressive,  +/-­‐  placement  of  a  CVC,  and  admin  of  inotropes,  blood  transfusions  

•  Usual  Care—guided  by  clinical  team  

Primary  End  Point:  60  day  in-­‐hospital  mortality  

Page 51: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Aims  •  Tested  sequen=ally  whether  protocol  based  care,  either  EGDT  and  standard  therapy  groups  combined,  was  superior  to  usual  care  

•  Tested  whether  protocol  based  EGDT  was  superior  to  protocol  based  standard  therapy  

•  Secondary  outcomes  :    90  day  and  1  year  mortality,  dura=on  of  CV  failure,  ARF,  ARF,  hospital  LOS  and  discharge  disposi=on  

Page 52: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Results  •  Enrolled  1341  pa=ents  •  439  assigned  to  protocol-­‐based  EGDT  •  446  assigned  protocol-­‐based  standard  therapy  •  456  assigned  to  usual  care  

Page 53: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Resuscitation  Strategies  •  Monitoring  of  CVPs    •  CVCs  placed  in  56.5%  of  protocol  group  and  57.9%  of  usual  care  group  •  Placement  occurred  later  than  EGDT    

•  IVF  Resuscita=on  •  2.8L  vs  3.3  L  vs  2.3  L  

•  Vasopressors  •  54.9%  vs  52.2%  vs  44.1%  

•  Inotropes—Dobutamine    •  8.0%  vs  1.1%  vs  0.9%  

•  Blood  transfusions  •  14.4%  vs  8.3%  vs  7.5%  

Page 54: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Results  @  60  days  •  EGDT:  92  deaths  –  21.0%  •  Protocol  based,  std  therapy:  81  deaths  =18.2%  •  Usual  care:  86  deaths  =18.9%  

•  Rela=ve  risk  with  EGDT  vs  protocol:  1.15,  CI  0.88-­‐1.51,  P  =  0.31  •  Rela=ve  risk  with  protocol  based  vs  usual  care:  1.04,  CI  0.82-­‐1.31,  P=0.83  

•  There  were  no  sign  differences  in  90  day  mortality,  1  year  mortality,  LOS  in  ICU  or  hospital,  CV  failure,  respiratory  failure  or  discharge  disposi=on  

Page 55: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 56: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 57: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Discussion  •  Two  protocol  based  approaches  !  higher  requirement  for  ICU  and  renal  replacement  therapy  

•  No  significant  differences  in  mortality  between  all  group  •  With  EGDT,  more  =me  is  spent  on  the  central  venous  catheter  

•  EGDT  required  more  dobutamine  and  gave  more  transfusion  •  Equates  to  more  money  spent  

Page 58: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Limitations  •  Rivers’  cohort  were  older,  with  more  pre-­‐exis=ng  heart  and  liver  disease  as  well  as  higher  ini=al  lactate  levels    

•  Non-­‐adherence  to  protocol  •  11.9%  in  EGDT  

•  6.8%  CVC  difficul=es  

•  4.4%  in  protocol  based    •  Changes  in  past  decade  in  cri=cal  care  and  resuscita=on  may  be  confounding    

•  Fluid  resuscita=on  prior  to  randomiza=on    

•  Time  to  receiving  an=bio=cs    

Page 59: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Goal-­‐Directed  Resuscitation  for  Patients  with  Early  Septic  Shock  ARISE  Trial  

NEJM  2014  

Peake  at  al.    

Page 60: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Methods  •  51  centers  (mostly  in  Australia  and  New  Zealand)  •  Randomly  assigned  pa=ents  presen=ng  to  the  ED  with  early  sep=c  shock  •  1)  EGDT  •  2)  Standard  care—guided  by  the  trea=ng  clinical  team  (ScvO2  measurements  were  not  permiyed  during  ini=al  6  hours)  

•  Primary  outcome:  All-­‐cause  mortality  within  90  days  arer  randomiza=on  

Page 61: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Results  •  1600  enrolled  pa=ents  •  796  assigned  to  the  EGDT  group  •  804  assigned  to  the  usual-­‐care  group  

•  Primary  outcome  data  were  available  for  more  than  99%  of  pa=ents  

Page 62: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Results  •  EGDT  vs  Usual-­‐Care  •  Received  a  larger  mean  volume  of  IVF  in  first  6  hours  than  usual-­‐care  group  •  1964+/-­‐1415ml  vs  1713+/-­‐1401ml  

•  More  likely  to  receive  vasopressor  infusions  •  66.6%  vs  57.8%  

•  Red  cell  transfusions  •  13.6%  vs  7.0%  

•  Dobutamine  •  15.4%  vs  2.6%  

P  <0.001  for  all  comparisons  

Page 63: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

90  days  •  EGDT  vs  Usual-­‐care  group  •  147  vs  150  deaths  •  Rate  of  death:  18.6  vs  18.8%  

•  No  significant  difference  in  survival  =me,  in-­‐hospital  mortality,  dura=on  of  organ  support  or  length  of  hospital  stay    

Page 64: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%
Page 65: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Conclusion  •  In  cri=cally  ill  pa=ents  presen=ng  to  the  ED  with  early  sep=c  shock,  EGDT  did  not  reduce  all-­‐cause  mortality  at  90  days  

•  No  significant  differences  in  28  day  or  in  hospital  mortality,  dura=on  of  organ  support    or  LOS  

Page 66: Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% • Time4dependentmedical%emergency% • Body’s%response%to%an%infec=on%injures%its%own%=ssues%and%

Caveats  to  ARISE  •  All  pa=ents  received  1  to  2  L  of  fluids  before  randomiza=on  (in  the  USA,  fluid  resuscita=on  tends  to  be  much  more  conserva=ve)  •  Difference  was  less  than  300  cc  b/w  2  arms  

•  Suggests  that  our  prac=ce  of  giving  fluids  has  changed    

•  Pa=ent  popula=on  different  than  original  study  •  Lower  rate  of  chronic  disease  •  Beyer  func=onal  status  •  Lower  propor=on  of  NH  residents