Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% •...
Transcript of Dr#Mai#Nguyen# CSTEM3#MMUH# 21/8/2015 · Introduction • Common%–20%%of%ED%referrals% •...
Dr Mai Nguyen
CSTEM 3 MMUH 21/8/2015
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
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
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
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)
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%
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
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
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
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
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
Compliance reduces rela=ve risk of death by 46.6%
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***
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
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
Further Management • Urgent Referral to specialty • Urgent CT -‐ ?intra-‐abdominal sepsis, ?necro=zing fascii=s
• LMWH for thrombo-‐prophylaxis
• IV PPI – reduce stress-‐ulcers
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
What about the Tricky Patients? • CCF • Dialysis • Pre-‐eclampsia and sepsis
• Same principles –bolus + review
• Use smaller volumes more oren
• Senior/specialty advice
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
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
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
Early Goal Directed Therapy
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
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
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%
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 = €€€
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
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.
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
Early Goal-‐directed Therapy in the Treatment of Severe Sepsis and Septic Shock
NEJM 2001
Rivers et al.
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)
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)
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
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
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
A Randomised Trial of Protocol-‐Based Care for Early Septic Shock ProCESS Trial NEJM 2014
Yealy et al
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
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
Results • Enrolled 1341 pa=ents • 439 assigned to protocol-‐based EGDT • 446 assigned protocol-‐based standard therapy • 456 assigned to usual care
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%
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
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
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
Goal-‐Directed Resuscitation for Patients with Early Septic Shock ARISE Trial
NEJM 2014
Peake at al.
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
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
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
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
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
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