Post on 02-Feb-2018
Sepsis overviewSepsis overviewDr. Tsang Dr. Tsang HinHin HungHungMBBS FHKCP FRCPMBBS FHKCP FRCP
EpidemiologyEpidemiologySepsis, severe sepsis, septic shockSepsis, severe sepsis, septic shockPathophysiologyPathophysiology of sepsisof sepsisRecent researches and advancesRecent researches and advancesFrom bench to bedsideFrom bench to bedsideSepsis bundleSepsis bundle
Angus DC. Angus DC. CritCrit Care Med.Care Med. 2001;29(7):13032001;29(7):1303--1310.1310.
TodayToday
>750,000 cases of severe
sepsis/year in the US*
FutureFuture
200,000
400,000
600,000
800,000
1,000,000
1,200,000
1,400,000
1,600,000
1,800,000
2001 2025 2050
Year
100,000
200,000
300,000
400,000
500,000
600,000Severe Sepsis CasesUS Population
Seps
is C
ases
Tota
l US
Popu
latio
n/1,
000
Incidence projected to increase by 1.5% per year
Severe sepsis in USSevere sepsis in US
Angus DC. Angus DC. CritCrit Care Med.Care Med. 2001;29(7):13032001;29(7):1303--1310.1310.
Comparable Global Comparable Global EpidemiologyEpidemiology
95 cases per 100,000 95 cases per 100,000 •• 2 week surveillance 2 week surveillance •• 206 French ICUs 206 French ICUs
95 cases per 100,000 95 cases per 100,000 •• 3 month survey 3 month survey •• 23 Australian/New 23 Australian/New
Zealand ICUs Zealand ICUs 51 cases per 100,00051 cases per 100,000•• England, Wales and England, Wales and
Northern Ireland. Northern Ireland.
Comparison With Comparison With Other Major DiseasesOther Major Diseases
†National Center for Health Statistics, 2001. §American Cancer Society, 2001. *American Heart Association. 2000. ‡Angus DC et al. Crit Care Med. 2001;29(7):1303;29(7):1303--13101310.
AIDS* Colon BreastCancer§
CHF† Severe Sepsis‡
Cas
es/1
00,0
00
0
50
100
150
200
250
300
Incidence of Severe Sepsis Mortality of Severe Sepsis
0
50,000
100,000
150,000
200,000
250,000
Dea
ths/
Year
AIDS* SevereSepsis‡
AMI†Breast Cancer§
What is Sepsis?What is Sepsis?
Systemic inflammatory response Systemic inflammatory response syndrome syndrome InfectionInfection
Definition of sepsisDefinition of sepsisSepsis is considered present if infection is highly suspected Sepsis is considered present if infection is highly suspected or proven and two or more of the following or proven and two or more of the following systemic systemic inflammatory response syndromeinflammatory response syndrome (SIRS) criteria are met(SIRS) criteria are met
Heart rateHeart rate > 90 beats per minute (tachycardia)> 90 beats per minute (tachycardia)
Body temperatureBody temperature < 36 < 36 °°C (96.8 C (96.8 °°F) or > 38 F) or > 38 °°C (100.4 C (100.4 °°F) F) (hypothermia or fever) (hypothermia or fever)
Respiratory rateRespiratory rate > 20 breaths per minute or, on blood gas, > 20 breaths per minute or, on blood gas, a PaCO2 less than 32 mm Hg (4.3 a PaCO2 less than 32 mm Hg (4.3 kPakPa) () (tachypnoeatachypnoea or or hypocapnoeahypocapnoea due to hyperventilation) due to hyperventilation)
White blood cell countWhite blood cell count < 4000 cells/mm< 4000 cells/mm³³ or > 12000 or > 12000 cells/mmcells/mm³³ or greater than 10% band forms (immature or greater than 10% band forms (immature white blood cells). white blood cells).
Definition of sepsisDefinition of sepsisSepsisSepsis is a serious medical condition characterized by a is a serious medical condition characterized by a wholewhole--body inflammatory statebody inflammatory state (called a systemic (called a systemic inflammatory response syndrome or SIRS) caused by inflammatory response syndrome or SIRS) caused by infection.infection.
Severe sepsis: sepsis + acute organ Severe sepsis: sepsis + acute organ dysfunction(organdysfunction(organhypoperfusionhypoperfusion))
Septic shock: sepsis + refractory arterial hypotension (SBP Septic shock: sepsis + refractory arterial hypotension (SBP <90mmHg)<90mmHg)
Septic shock
Severe sepsis
Sepsis
Mortality
Sepsis Sepsis –– a systemic disease!!a systemic disease!!
Infective agents
CytokinesCytokinessoluble (soluble (glyco)proteinsglyco)proteinsnonimmunoglobulinnonimmunoglobulin in in nature nature released by living cells of released by living cells of the hostthe hostact act nonenzymaticallynonenzymatically in in picomolarpicomolar to to nanomolarnanomolarconcentrations concentrations through specific receptors through specific receptors to regulate host cell to regulate host cell function.function.
Cytokine storm
Cardiovascular changes in septic shock.
Fluid TherapyFluid Therapy
Fluid resuscitation Fluid resuscitation
Colloids or crystalloids?Colloids or crystalloids?
Crystalloids vs. colloids in fluid resuscitation: A systematic review. Crit Care Med 1999; 27:200–210
The Saline versus Albumin Fluid Evaluation (SAFE) The Saline versus Albumin Fluid Evaluation (SAFE) Study investigators Study investigators
3497 patients were assigned to receive albumin 3497 patients were assigned to receive albumin
and 3500 to receive salineand 3500 to receive saline
Primary outcome: 28Primary outcome: 28--day mortalityday mortality
NEJM 2004
Kaplan-Meier Estimates of the Probability of Survival. P=0.96 for the comparison between patients assigned to receive albumin and those assigned to receive saline. NEJM 2004
Which Which vasopressorsvasopressors??
NoradrenalineNoradrenaline is better than is better than dopamine or adrenaline?dopamine or adrenaline?
Vasopressin is better?Vasopressin is better?
Effects of Dopamine, Norepinephrine,Effects of Dopamine, Norepinephrine,and Epinephrine on the and Epinephrine on the SplanchnicSplanchnic
CirculationCirculation in Septic Shockin Septic Shock
Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: Which is best? Crit Care Med 2003; 31:1659-1667
Low dose dopamine for Low dose dopamine for renal protection?renal protection?
Surviving sepsis campaign 2008Surviving sepsis campaign 2008
Use of steroid in sepsisUse of steroid in sepsis
Effect of treatment with low doses hydrocortisone and Effect of treatment with low doses hydrocortisone and fludrocortisonefludrocortisone on mortality in patients with septic shockon mortality in patients with septic shock
Annane et al, JAMA 2002
Hydrocortisone Therapy for Patients with Hydrocortisone Therapy for Patients with Septic Shock Septic Shock CORTICUS CORTICUS NEJM 2008NEJM 2008
Activated protein CActivated protein C
35
30
25
20
15
10
5
0
30.8%
24.7%
Placebo
(n-840)
Drotrecoginalfa
(activated) (n=850)
Mor
talit
y (%
)
6.1% absolute reduction in
mortality
Results: 28-Day All-Cause MortalityPrimary analysis results
2-sided p-value 0.005Adjusted relative risk reduction 19.4%Increase in odds of survival 38.1%
Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344:699-709
Mortality and APACHE II QuartileMortality and APACHE II Quartile
APACHE II Quartile*Numbers above bars indicate total deaths
05
101520253035404550
1st (3-19) 2nd (20-24) 3rd (25-29) 4th (30-53)
PlaceboDrotrecogin
Mor
talit
y (p
erce
nt)
26:33
57:49
58:48
118:80
Adapted from Figure 2, page S90, with permission from Bernard GR. Drotrecogin alfa (activated) (recombinant human activated protein C) for the treatment of severe sepsis. Crit Care Med 2003; 31[Suppl.]:S85-S90
Mortality and Numbers of Organs FailingMortality and Numbers of Organs Failing
PercentMortality
0
10
20
30
40
50
60
1 2 3 4 5
PlaceboDrotrecogin
Number of Organs Failing at Entry
Adapted from Figure 4, page S91, with permission from Bernard GR. Drotrecogin alfa (activated) (recombinant human activated protein C) for the treatment of severe sepsis. Crit Care Med 2003; 31[Suppl.]:S85-S90
Recombinant Human Activated Recombinant Human Activated Protein C (Protein C (rhAPCrhAPC))
High risk of deathHigh risk of death•• APACHE II APACHE II ≥≥ 2525•• SepsisSepsis--induced multiple organ induced multiple organ
failurefailure•• Septic shockSeptic shock•• Sepsis induced ARDSSepsis induced ARDS
No absolute contraindicationsNo absolute contraindicationsWeigh relative contraindicationsWeigh relative contraindications
6 Hour Resuscitation 6 Hour Resuscitation Golden hours for sepsis resuscitationGolden hours for sepsis resuscitation
Early IdentificationEarly IdentificationEarly Antibiotics Early Antibiotics and Culturesand CulturesEarly Goal Directed Early Goal Directed TherapyTherapy
Early Goal Directed TherapyEarly Goal Directed Therapy
The Importance of Early GoalThe Importance of Early Goal--DirectedDirectedTherapy for Sepsis Induced HypoperfusionTherapy for Sepsis Induced Hypoperfusion
Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368-1377
In-hospital mortality
(all patients)
0102030405060 Standard therapy
EGDT
28-day mortality
60-day mortality
NNT to prevent 1 event (death) = 6-8
Mor
talit
y (%
)
Do not delay resuscitation Do not delay resuscitation pending ICU admissionpending ICU admission
Intensive insulin therapyIntensive insulin therapy
The Role of IntensiveThe Role of IntensiveInsulin Therapy in the Critically IllInsulin Therapy in the Critically Ill
At 12 months, intensive At 12 months, intensive insulin therapy reduced insulin therapy reduced mortality by 3.4% mortality by 3.4% (P<0.04)(P<0.04)
van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients.N Engl J Med 2001;345:1359-67
In-h
ospi
tal s
urvi
val (
%)
100
00
Intensive treatment
Conventional treatment
Days after admission
80
84
88
92
96
50 100 150 200 250
P=0.01
Intensive insulin therapy in medical ICUIntensive insulin therapy in medical ICUvan den Berghe G, NEJM 2006
Multiple organ failure in sepsisMultiple organ failure in sepsis
Acute respiratory distress Acute respiratory distress syndrome syndrome –– ARDSARDSCirculatory failureCirculatory failureAcute renal failure Acute renal failure –– ARFARFLiver Liver derrangementderrangementCoagulopathyCoagulopathyEncephalopathyEncephalopathy
ARDS – Acute respiratory distress syndrome
Mechanical Ventilation of Mechanical Ventilation of SepsisSepsis--Induced ALI/ARDSInduced ALI/ARDS
0
5
10
15
20
25
30
35
40
6 ml/kg12 ml/kg
% M
orta
lity
ARDSnet Mechanical Ventilation ProtocolResults: Mortality
The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000;342:1301-1378
Renal failure in sepsisRenal failure in sepsis
Renal replacement Renal replacement therapytherapy
Blood purificationBlood purification
Transfusion Strategyin the Critically Ill
Hebert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999; 340:409-417
Other supportive therapies in Other supportive therapies in sepsissepsis
DVT prophylaxisDVT prophylaxis
Stress ulcer prophylaxisStress ulcer prophylaxis
Sedation and weaning from Sedation and weaning from ventilatorventilator
…………………………………………....
From Bench to BedsideFrom Bench to Bedside
Surviving Sepsis CampaignSurviving Sepsis Campaign
A global program to:A global program to:Evidence based guidelineEvidence based guideline
Implementation and educationImplementation and educationReduce mortality ratesReduce mortality ratesImprove standards of careImprove standards of care
Sepsis Bundle Approach
6 6 -- hour Severe Sepsis/hour Severe Sepsis/Septic Shock BundleSeptic Shock Bundle
Early Detection:Early Detection:•• Obtain serum lactate Obtain serum lactate
level.level.
Early Blood Early Blood CxCx/Antibiotics:/Antibiotics:•• within 3 hours of within 3 hours of
presentation. presentation.
Early EGDT: Early EGDT: Hypotension (SBP < 90, Hypotension (SBP < 90, MAP < 65) or lactate > 4 MAP < 65) or lactate > 4 mmol/L:mmol/L:•• initial fluid bolus 20initial fluid bolus 20--40 ml 40 ml
of crystalloid (or colloid of crystalloid (or colloid equivalent) per kg of body equivalent) per kg of body weight.weight.
Vasopressors:Vasopressors:•• Hypotension not Hypotension not
responding to fluidresponding to fluid•• Titrate to MAP > 65 Titrate to MAP > 65
mmHg.mmHg.
Septic shock or lactate > Septic shock or lactate > 4 mmol/L:4 mmol/L:•• CVP and ScvOCVP and ScvO22 measured.measured.•• CVP maintained >8 CVP maintained >8
mmHg.mmHg.•• MAP maintain > 65 MAP maintain > 65
mmHg.mmHg.
ScvO2<70%with CVP > 8 ScvO2<70%with CVP > 8 mmHg, MAP > 65 mmHg:mmHg, MAP > 65 mmHg:•• PRBCs if hematocrit < PRBCs if hematocrit <
30%. 30%. •• InotropesInotropes..
24 24 -- hour Severe Sepsis hour Severe Sepsis and Septic Shock Bundleand Septic Shock Bundle
Glucose control:Glucose control:•• maintained on average <150 mg/dL (8.3 maintained on average <150 mg/dL (8.3 mmolmmol/L)/L)
Drotrecogin alfa (activated):Drotrecogin alfa (activated):•• administered in high risk patients and without administered in high risk patients and without
contraindicationcontraindication
Steroids:Steroids:•• for septic shock requiring continued use of vasopressors for septic shock requiring continued use of vasopressors
for equal to or greater than 6 hours.for equal to or greater than 6 hours.
Lung protective strategy:Lung protective strategy:•• Maintain plateau pressures Maintain plateau pressures << 30 cm H30 cm H22O, tidal volume 6O, tidal volume 6--
8ml/kg and optimal PEEP8ml/kg and optimal PEEP
ConclusionConclusionSevere sepsis is a common, expensive and Severe sepsis is a common, expensive and frequently fatal conditionfrequently fatal condition
Growing problem and leading cause of Growing problem and leading cause of deathdeath
A systemic diseaseA systemic disease
Sepsis bundle Sepsis bundle –– improve standards of care improve standards of care and reduce mortality rateand reduce mortality rate
Thank you
Mechanical Ventilation ofMechanical Ventilation ofSepsisSepsis--Induced ALI/ARDSInduced ALI/ARDSReduce tidal volume over 1Reduce tidal volume over 1––2 hrs to 6 ml/kg predicted 2 hrs to 6 ml/kg predicted body weightbody weightMaintain inspiratory plateau Maintain inspiratory plateau pressure < 30 cm Hpressure < 30 cm H2200
Mechanical Ventilation ofMechanical Ventilation ofSepsisSepsis--Induced ALI/ARDSInduced ALI/ARDSMinimum PEEPMinimum PEEP•• Prevent end expiratory lung Prevent end expiratory lung
collapsecollapseSetting PEEPSetting PEEP•• FIO2 requirementFIO2 requirement•• Thoracopulmonary Thoracopulmonary
compliancecompliance