septic shock update

1. Sepsis Guidelines 2015Sepsis Guidelines 2015
Dr. T.R.ChandrashekarDr. T.R.Chandrashekar
IntensivistIntensivist, Liver transplantation., Liver transplantation.
BMC & RI super-specialty Hospital.BMC & RI super-specialty Hospital.
Bangalore.Bangalore.

2. Case ScenarioCase Scenario
 35 year old male patient brought to ICU with 3 day old35 year old male patient brought to ICU with 3 day old
perforation,perforation, Posted for emergency LapratomyPosted for emergency Lapratomy
 Has chills with feverHas chills with fever
 Tachypneic- RR 40/mt, has respiratory distress,Tachypneic- RR 40/mt, has respiratory distress,
 Tense abdomen, bilateral crepts,Tense abdomen, bilateral crepts,
 Spo2 on 4l/O2 on RBM 95%,Spo2 on 4l/O2 on RBM 95%,
 Pulse 130/mt well felt, BP 80/60 mm Hg, Restless,Pulse 130/mt well felt, BP 80/60 mm Hg, Restless,
 InvestigationsInvestigations
 WBC – 19,000 T.B 3.5, Enzymes NormalWBC – 19,000 T.B 3.5, Enzymes Normal
 SC-2.0 INR 2.0, Platelets 1.2 lacSC-2.0 INR 2.0, Platelets 1.2 lac
 Lactate 5.0Lactate 5.0
Is he in septic shock ?Is he in septic shock ?

3. Terminology andTerminology and
DefinitionsDefinitions

4. Shock definitionShock definition
 ShockShock is defined as a life-threatening, generalizedis defined as a life-threatening, generalized
maldistributionmaldistribution of blood flow resulting in failure toof blood flow resulting in failure to
deliver and/or utilize adequate amounts of oxygen,deliver and/or utilize adequate amounts of oxygen,
leading to tissue dysoxia.leading to tissue dysoxia.
 Hypotension [SBPHypotension [SBP << 90 mmHg, SBP decrease of 4090 mmHg, SBP decrease of 40
mmHg from baseline, or mean arterial pressuremmHg from baseline, or mean arterial pressure
(MAP)(MAP) << 65 mmHg], while commonly present,65 mmHg], while commonly present,
shouldshould not be required to define shocknot be required to define shock.. ShockShock
requires evidence of inadequate tissue perfusion onrequires evidence of inadequate tissue perfusion on
physical examinationphysical examination..

5. Relationship Of Infection, SIRS, Sepsis SevereRelationship Of Infection, SIRS, Sepsis Severe
Sepsis and Septic ShockSepsis and Septic Shock
SIRSINFECTION
PANCREATITIS
BURNS
TRAUMA
OTHER
SEPSIS
SEVERE
SEPSIS
SEPTIC
SHOCKBacteria
Fungus
Parasites
Virus

6. Sepsis: Defining a Disease Continuum
A clinical response arising from a nonspecific
insult, including ≥ 2 of the following:
•Temperature ≥38o
C or ≤36o
C
•HR ≥90 beats/min
•Respirations ≥20/min / PCo2 ≤ 30 cms H2O
•WBC count ≥12,000/mm3
or
≤4,000/mm3
or >10% immature neutrophils
SIRS
Systemic Inflammatory Response Syndrome
SIRS with a presumed or
confirmed infectious process
SepsisSepsisSIRSSIRSInfectionInfection
SevereSevere
SepsisSepsis
SEPTIC
SHOCK
Inflammatory response to
microorganisms or invasion
of normally sterile tissues

7. SepsisSepsisSIRSSIRSInfection/Infection/
TraumaTrauma
SevereSevere
SepsisSepsis
Sepsis with ≥1 sign of organ
failure
Cardiovascular ( hypotension)
Lungs: early fall in arterial PO2,
(ARDS):
Kidneys -oliguria, anuria,
azotemia, proteinuria SC more
than 2
Liver TB more than 2
Digestive tract- vomiting,
diarrhea and ileus
Brain - confusion
SEPTICSEPTIC
ShockShock
Hypotension despite
adequate fluid
resuscitation/
Requiring
vasopressors/
Inotropes
Disease continuum

8. Arterial hypotension
Tachycardia
Increased cardiac output
/low SVR/high SvO2
Altered skin perfusion
Decreased urine output
Hyperlactatemia –
increased base deficit
Altered WBC count
Increased CRP,
IL-6,
PCT concentrations
Rigor– fever
(sometimes hypothermia)
Tachypnea
/respiratory alkalosis
Positive fluid balance – edema
General signs & symptoms
General inflammatory
reaction
Hemodynamic
alterations
Signs of organ dysfunctionSigns of organ dysfunction
Hypoxemia
Coagulation abnormalities
Altered mental status
Expanded signs of SIRSExpanded signs of SIRS

9. Acute Organ DysfunctionAcute Organ Dysfunction
Tachycardia
Hypotension
↑ CVP
↑ PAOP
Jaundice
↑ Enzymes
↓ Albumin
↑ PT
Altered
Consciousness
Confusion
Psychosis
Tachypnea
PaO2 <70 mm Hg
SaO2 <90%
PaO2/FiO2 ≤300
Oliguria
Anuria
↑ Creatinine
↓ Platelets
↑ PT/APTT
↓ Protein C
↑ D-dimer
Balk. Crit Care Clin 2000;16:337-52

10. PathophysiologyPathophysiology

11. Pathogenesis of shockPathogenesis of shock
Microcirculatory Mitochondrial dysfunction
Cardiac dysfuction, microemboli, microvasular injury,
increasaed Nitric oxide- vasoplegia
Cytokines & inflammatory mediator cascade
Interaction with human cells- macrophages
Monocytes, Neutrophils, Endothelial cells
Infectious trigger
Sepsis is a disease of the microcirculation

12. Pathogenisis of SepsisPathogenisis of Sepsis
TRIGGER
INTERACTION
WITH HUMAN
CELLSCoagulation
abnorm
alities
Coagulation
abnorm
alities
Pro-
inflammatory
Anti
inflammatory
Endothelial injury
Nitric oxide
over production
Cardiac dysfunction
Hypotension
Micro-emboli
Hypoperfusion
Mitochondrial
dysfunction
Organ injury MODS
Death
Endothelial injury
Nitric oxide
over production
Cardiac dysfunction
Hypotension
Micro-emboli
Hypoperfusion
Mitochondrial
dysfunction
Organ injury MODS
Death
Primary
mediators
Secondary
mediators
Monocytes
Macrophages
Neutophils
Plasma
Endothelial cells

13. Immune Response to Injury/ InfectionImmune Response to Injury/ Infection
Infection/injuryInfection/injury
Prompt coordinatedPrompt coordinated
protectsprotects
Excessive, poor regulationExcessive, poor regulation
harmsharms
Deficient, weakDeficient, weak
Inf establishedInf established
Immunologic Cascade
1.1. Cytokine releaseCytokine release
2.2. Activation of macrophage/ neutrophilsActivation of macrophage/ neutrophils
3.3. Activation of neuro endocrine reflexActivation of neuro endocrine reflex
4.4. Activation of plasma protein cascadesActivation of plasma protein cascades
(Complement,Coagulation, fibrinolysis)(Complement,Coagulation, fibrinolysis)

14. Toll receptors (TLR)Toll receptors (TLR)
 Key mediators of the innate immune system
 Expressed on macrophage, dendritic cells,
neutrophils, endothelial cells and mucosal
epithelial cells
 TLR are transmembrane proteins with the ability
to promote signaling pathways downstream,
triggering cytokine release and neutrophil
activation and stimulating endothelial cells

15. Why different bacteria stimulateWhy different bacteria stimulate
different Effects ?different Effects ?
Most microorganisms present more than one TLR
ligand, therefore, it is likely that microbes with
differing patterns of molecular motifs can cause
differential activation of a number of TLRs, allowing
differential responses to various classes of pathogen.
Immunosuppressed
Extremes of age
Malnutrition
Alcohol, Drug Abuse
Malignancy
HIV/AIDS
Chronic Health Issues –
Diabetes, Liver Failure, Heart
Disease,
Corticosteroids, Chemotherapy
Multiple invasive procedures
or invasive lines

16. MicrocirculationMicrocirculation

17. Key steps in oxygen cascadeKey steps in oxygen cascade
Macrocirculation
Microcirculation

18. Why the microcirculation is important inWhy the microcirculation is important in
shockshock..
1. It is where oxygen
exchange takes place.
2. It plays a central role in
the immune system.
3. During sepsis and shock
it the first to go and last
to recover.
4. Rescue of the
microcirculation =
resuscitation end-point.

19. Local
Shunt
Precapillary sphincter= vasodilatation/
vasoconstriction
cell = cellular utilization O2 in sepsis
Interstitial matrix= edema causes barrier to O2
delivery to the cell
Postcapillary venule
Microcirculatory defects

20. Spronk P, Zandstra D, Ince C (2004) Critical Care 8:462-468
Sepsis is a disease of the microcirculation

21. MicrocirculationMicrocirculation
 Microvascular abnormalities appear early in
septic shock, and their persistence is closely
associated with organ failure and prognosis.
 Septic shock perfusion is characterized by
heterogeneity of organ perfusion and the
discrepancy between the overall
hemodynamics and local blood flow

22. MicrocirculationMicrocirculation
 Global parameters such as heart rate and
mean arterial pressure (MAP) cannot identify
or quantify microcirculatory abnormalities.
 Impaired microcirculatory perfusion may
persist despite correction of systemic oxygen
delivery variables like MAP or cardiac
output.

23. Markers of Macro-circulationMarkers of Macro-circulation
and Micro circulationand Micro circulation
Resuscitation end pointsResuscitation end points

25. Orthogonal
polarization
spectral (OPS)
imaging
Gastric
Tonometry
Microdialysis
Sublingual
capnometry
ScVO2
Base deficit
Mediators

26. Microcirculation assessmentMicrocirculation assessment
 Tissue perfusionTissue perfusion
 Gastric tonometryGastric tonometry

27. Orthogonal polarizationOrthogonal polarization
spectral (OPS) imagingspectral (OPS) imaging

28. Capillary flow in sepsisCapillary flow in sepsis

29. Understanding oxygen delivery toUnderstanding oxygen delivery to
cellular levelcellular level

30. Matching deliveryMatching delivery
==
Requirement
Assessment of Oxygenation
O2 delivery is a Cardio-Respiratory function

31. DODO22/VO/VO22 Oxygen delivery vs RequirementOxygen delivery vs Requirement
Patients have to be kept well above the Critical Point so that
Does not plateau- Consumption remains supply
dependent even with supraphysiological levels
VO2 is supply
dependent
VO2 is supply independent
Oxygenation to the tissue is not compromised
MMDS and O2 extraction failure
Shunting due to micro-emboli

32. OO22
COCO22
Alveoli
PAO2
Atmospheric air /FIO2
Water vapour is added- Nose/
upper airway
Alveolar Oxygen
PaO2 (2% dissolved O2)
Measured in ABG
P(A-
a)O2
SaO2
O.
D.
C.
Temp
H+
2,3-DPG
98% of O2 is Hb bound-
1.34 x Hb% x Sao2CaO2-oxygen content +PaO2 x 0.003ml
Oxygen Delivery=CaO2 x Cardiac output
Cardiac output - SV x HR
Preload / Afterload/ Contractility
Oxygen delivery DO2 is a
Cardio- Respiratory Function
=

33. Volume Vessel
tone
Heart
function
If shock is prolonged, mechanisms of shock are combined
Physiologic Classification ofPhysiologic Classification of
Acute Circulatory InsufficiencyAcute Circulatory Insufficiency
Fluids / blood Vasopressors Inotropes

34. TIMETIME
isis
TISSUETISSUE
Oxygen DonOxygen Don’t Go’t Go
Where the Blood Won’t FlowWhere the Blood Won’t Flow!!
From these two statements three things are obvious
Early therapy before mitochondria gets damaged.
Macro circulation should be optimised first.
Micro circulation optimisation to prevent
Mitochondrial injury is the target

35. Sepsis Management BundleSepsis Management Bundle
Macrocirculation optimization toMacrocirculation optimization to
correct Microcirculationcorrect Microcirculation

36. Sepsis Management BundleSepsis Management Bundle
First 3 hours bundleFirst 3 hours bundle
 Measure lactate level
 Obtain blood cultures prior to administration of
antibiotics
 Administer broad spectrum antibiotics
 Administer 30ml/kg crystalloid for hypotension
or lactate ≥4mmol/L

37. Time of presentation
 “Time of presentation” is defined as the time of
triage in the emergency department or, if
presenting from another care venue, from the
earliest chart annotation consistent with all
elements of severe sepsis or septic shock
ascertained through chart review.

38. TO BE COMPLETED WITHIN 6 HOURS
( Bundle) OF TIME OF PRESENTATION
 Apply vasopressors (for hypotension that does
not respond to initial fluid resuscitation) to
maintain a mean arterial pressure (MAP)
≥65mmHg
 In the event of persistent hypotension after
initial fluid administration (MAP < 65 mm Hg)
or if initial lactate was ≥4 mmol/L, re-assess
volume status and tissue perfusion and
document findings according to Table 1.
 Re-measure lactate if initial lactate elevated.

39. DOCUMENT REASSESSMENT OF VOLUMEDOCUMENT REASSESSMENT OF VOLUME
STATUS AND TISSUE PERFUSION WITHSTATUS AND TISSUE PERFUSION WITH
EITHEREITHER
Repeat focused exam (after initial fluid resuscitation) byRepeat focused exam (after initial fluid resuscitation) by
licensed independent practitioner including vital signs,licensed independent practitioner including vital signs,
cardiopulmonary, capillary refill, pulse, and skin findings.cardiopulmonary, capillary refill, pulse, and skin findings.
OR TWO OF THE FOLLOWINGOR TWO OF THE FOLLOWING::
Measure CVP / Measure ScvOMeasure CVP / Measure ScvO22 / Bedside/ Bedside
cardiovascular ultrasoundcardiovascular ultrasound
Dynamic assessment of fluid responsiveness with passiveDynamic assessment of fluid responsiveness with passive
leg raise or fluid challengeleg raise or fluid challenge
Of note, the 6-hour bundle has been updated;
The 3-hour SSC bundle is not affected.

40. DiagnosisDiagnosis
 For patients suspected to be in severe sepsis or septic shock,For patients suspected to be in severe sepsis or septic shock,
body fluid culturesbody fluid cultures should be obtained as quickly as is feasible.should be obtained as quickly as is feasible.
Collect at leastCollect at least 2 sets of aerobic and anaerobic blood2 sets of aerobic and anaerobic blood
culturescultures; these should be drawn; these should be drawn before giving antibioticsbefore giving antibiotics -- as-- as
long as cultures can be collected without delaying antimicrobiallong as cultures can be collected without delaying antimicrobial
therapy bytherapy by >45 minutes>45 minutes..
 At least one blood culture bottle set should be collectedAt least one blood culture bottle set should be collected
percutaneouslypercutaneously (through a needle stick), and one drawn(through a needle stick), and one drawn fromfrom
each venous or arterial cathetereach venous or arterial catheter (IVs, dialysis access, central(IVs, dialysis access, central
line, surgical port, arterial line, etc).line, surgical port, arterial line, etc).
 If a line or device has been placed in the last 48 hours, it can beIf a line or device has been placed in the last 48 hours, it can be
considered non-infected and no culture drawn.considered non-infected and no culture drawn.
 Other culturesOther cultures (e.g., urine) should be collected, if clinically(e.g., urine) should be collected, if clinically
indicated, with the same imperative to avoid undue delay ofindicated, with the same imperative to avoid undue delay of
antibiotics.antibiotics.

41. DiagnosisDiagnosis
 In the uncommon situation in which invasive candidiasisIn the uncommon situation in which invasive candidiasis
is being considered as a cause of sepsis, collect blood foris being considered as a cause of sepsis, collect blood for
the the 1,3 beta-D-glucan assay1,3 beta-D-glucan assay, and/or the, and/or the mannan andmannan and
anti-mannan antibody assaysanti-mannan antibody assays, which can help diagnose, which can help diagnose
invasive candida infections.invasive candida infections.
AppropriateAppropriate imaging studiesimaging studies be performed quickly, tobe performed quickly, to
help confirm potential sources of infection.help confirm potential sources of infection.

42. Source ControlSource Control
 Evaluate patient for a focused infectionEvaluate patient for a focused infection
amendable to source control measuresamendable to source control measures
including abscess drainage or tissueincluding abscess drainage or tissue
debridement.debridement.
• Move rapidlyMove rapidly
• Consider physiologic upset of measureConsider physiologic upset of measure
• Intravascular access devicesIntravascular access devices

43. Antibiotic TherapyAntibiotic Therapy
 Begin intravenous antibiotics within firstBegin intravenous antibiotics within first
hour of recognition of severe sepsis.hour of recognition of severe sepsis.

44. Antibiotic TherapyAntibiotic Therapy
 “Hit hard’ with a high dose of broad-spectrum
antibiotic
 “Get to the point’: take pharmacodynamics into
account
 “Focus, focus, focus’: tailor or stop therapy according
to microbiological results
 “Listen to your hospital’: tailor antibiotic policy
regularly
 “Look at your patient’: administer antibiotics according
to comorbidities, intubation period and previous
antibiotic exposure

45. AntibioticsAntibiotics
Always look at you
local organisms and
resistance patterns

46. Antibiotic TherapyAntibiotic Therapy
Reassess antimicrobial regimen at 48-Reassess antimicrobial regimen at 48-
72 hrs72 hrs
• Microbiologic and clinical dataMicrobiologic and clinical data
• Narrow-spectrum antibioticsNarrow-spectrum antibiotics
• Non-infectious cause identifiedNon-infectious cause identified
• Prevent resistance, reduce toxicity,Prevent resistance, reduce toxicity,
reduce costsreduce costs

47. Fluid therapyFluid therapy
Initial fluid challenge in sepsis-induced tissueInitial fluid challenge in sepsis-induced tissue
hypoperfusion (hypotension or elevated lactate)hypoperfusion (hypotension or elevated lactate)
A minimum of 30ml/kg of crystalloidsA minimum of 30ml/kg of crystalloids
(a portion of this may be albumin equivalent)(a portion of this may be albumin equivalent)

48. Three different scenariosThree different scenarios
2- Patients in the ER for high suspicion of septic shock2- Patients in the ER for high suspicion of septic shock
3- Patients in the ICU, already resuscitated for several hours or days3- Patients in the ICU, already resuscitated for several hours or days
1- Patients in the ER for acute blood losses or body fluid losses1- Patients in the ER for acute blood losses or body fluid losses

49. 3-3- Patients in the ICU, already resuscitated for sePatients in the ICU, already resuscitated for several hours or daysveral hours or days
How to deal with this therapeutic dilemma?
PredictionPrediction
of volume responsiveness ?of volume responsiveness ?
Fluid challenge ?Fluid challenge ?
- with hemodynamic instability requiring therapy- with hemodynamic instability requiring therapy
- without certainty of volume responsiveness- without certainty of volume responsiveness
- with potential risks of pulmonary edemawith potential risks of pulmonary edema
and/or excessive cumulative fluid balanceand/or excessive cumulative fluid balance

50. A fluid challenge
 A fluid challenge is a method of identifying
those patients likely to benefit from an increase
in intravenous volume in order to guide further
volume resuscitation. It is a dynamic test of the
circulation. The use of a ‘test’ that uses a small
amount of fluid to assess the volume respon-
siveness may reduce the risk of a too liberal fluid
strategy and the possible consequences of fluid
overload

52. Fluid challengeFluid challenge
 250ml or 3ml/kg over 5 to 10 minutes250ml or 3ml/kg over 5 to 10 minutes
 500ml in 30 min500ml in 30 min
 CVP increase by 2 cms of h2oCVP increase by 2 cms of h2o
 ScVO2 increase by 4%ScVO2 increase by 4%
 SV by 10 to 15 %SV by 10 to 15 %
 Increase in MAP UOIncrease in MAP UO

53. Passive Leg RaisingPassive Leg Raising
45 °45 °
Venous blood shiftVenous blood shift
(Rutlen et al.(Rutlen et al. 19811981,, Reich et al. 1989)Reich et al. 1989)
Increase in right ventricular preloadIncrease in right ventricular preload (Thomas et al 1965)
Increase in left ventricular preloadIncrease in left ventricular preload (Rocha 1987, Takagi 1989, De Hert 1999, Kyriades 1994 )
Transient effectTransient effect (Gaffney 1982)(Gaffney 1982)
PLR could be used as a test to detect volume responsivenessPLR could be used as a test to detect volume responsiveness
rather than as a therapyrather than as a therapy

54. Parameters to guide fluidParameters to guide fluid
administrationadministration

56. Vasopressors / InotropesVasopressors / Inotropes
..

57. VasopressorsVasopressors
 VasopressorsVasopressors should be begun initially to target a mean arterialshould be begun initially to target a mean arterial
pressure of 65 mm Hg (pressure of 65 mm Hg (Grade 1CGrade 1C).).
 AnAn arterial catheterarterial catheter for hemodynamic monitoring should befor hemodynamic monitoring should be
placed as soon as practical, if resources are available, for allplaced as soon as practical, if resources are available, for all
patients requiring vasopressors (ungraded recommendation).patients requiring vasopressors (ungraded recommendation).
 NorepinephrineNorepinephrine (Levophed) should be provided as the first-line(Levophed) should be provided as the first-line
vasopressor (vasopressor (Grade 1BGrade 1B).).
 EpinephrineEpinephrine is considered the next-line agent for septic shockis considered the next-line agent for septic shock
after norepinephrine in the Surviving Sepsis Guidelines. Whenafter norepinephrine in the Surviving Sepsis Guidelines. When
norepinephrine is insufficient to maintain MAP 65 mm Hg,norepinephrine is insufficient to maintain MAP 65 mm Hg,
epinephrine should be added to or substituted forepinephrine should be added to or substituted for
norepinephrine (norepinephrine (Grade 2BGrade 2B))..

58. VasopressinVasopressin
 VasopressinVasopressin at 0.03 units/minute is appropriate to useat 0.03 units/minute is appropriate to use
with norephinephrine, either to improve perfusionwith norephinephrine, either to improve perfusion
(increase MAP) or to reduce the required dose of(increase MAP) or to reduce the required dose of
norepinephrine (ungraded recommendation).norepinephrine (ungraded recommendation).
 Vasopressin is not recommended for use as a singleVasopressin is not recommended for use as a single
vasopressor for septic shock (ungradedvasopressor for septic shock (ungraded
recommendation).recommendation).
 Vasopressin doses higher than 0.03 - 0.04 units/min areVasopressin doses higher than 0.03 - 0.04 units/min are
recommended to be reserved only for dire situations ofrecommended to be reserved only for dire situations of
septic shock refractory to standard doses of multipleseptic shock refractory to standard doses of multiple
vasopressors (ungraded recommendation).vasopressors (ungraded recommendation).

59. DobutamineDobutamine
 DobutamineDobutamine should be tried for patients in septic shock whoshould be tried for patients in septic shock who
have low cardiac output with high filling pressures while onhave low cardiac output with high filling pressures while on
vasopressors, or who have persistent evidence of hypoperfusionvasopressors, or who have persistent evidence of hypoperfusion
after attaining an adequate mean arterial pressure andafter attaining an adequate mean arterial pressure and
intravascular volume (with or without vasopressors).intravascular volume (with or without vasopressors).
 A dobutamine infusion up to 20 mcg/kg/min can be added toA dobutamine infusion up to 20 mcg/kg/min can be added to
any vasopressor(s) in use. Dobutamine is also an appropriateany vasopressor(s) in use. Dobutamine is also an appropriate
first-line agent in patients with severe sepsis and low cardiacfirst-line agent in patients with severe sepsis and low cardiac
output, with a preserved mean arterial pressure (i.e., who are notoutput, with a preserved mean arterial pressure (i.e., who are not
in septic shock).in septic shock).
 Dobutamine is recommendedDobutamine is recommended notnot to be used to deliberately raiseto be used to deliberately raise
cardiac output to higher than normal levels in an attempt tocardiac output to higher than normal levels in an attempt to
improve perfusion.improve perfusion.

60. DopamineDopamine
 DopamineDopamine is suggested tois suggested to notnot be used as an alternative tobe used as an alternative to
norepinephrine in septic shock, except in highly selectednorepinephrine in septic shock, except in highly selected
patients such as those with inappropriately low heart ratespatients such as those with inappropriately low heart rates
(absolute or relative bradycardia) who are at low risk for(absolute or relative bradycardia) who are at low risk for
tachyarrhythmias. Dopamine is recommended to not betachyarrhythmias. Dopamine is recommended to not be
used in low doses in a so-called renal-protective strategy.used in low doses in a so-called renal-protective strategy.
 PhenylephrinePhenylephrine is recommended to not be used for septicis recommended to not be used for septic
shock, except when 1) septic shock persists despite the useshock, except when 1) septic shock persists despite the use
of 2 or more inotrope/vasopressor agents along with low-of 2 or more inotrope/vasopressor agents along with low-
dose vasopressin; 2) cardiac output is known to be high, ordose vasopressin; 2) cardiac output is known to be high, or
3) norepinephrine is considered to have already caused3) norepinephrine is considered to have already caused
serious arrhythmias.serious arrhythmias.

61. SteroidsSteroids
 Treat patients who still require vasopressors
despite fluid replacement with hydrocortisone
200-300 mg/day, for 7 days in three or four
divided doses or by continuous infusion.
 ACTH stimulation test isACTH stimulation test is notnot recommended.recommended.
 Steroid therapy may be weaned onceSteroid therapy may be weaned once
vasopressors are no longer required.vasopressors are no longer required.

62. Glucose ControlGlucose Control
 After initial stabilizationAfter initial stabilization
 Glucose < 180 mg/dLGlucose < 180 mg/dL
 Continuous infusion insulin and glucose orContinuous infusion insulin and glucose or
feeding (enteral preferred)feeding (enteral preferred)
 MonitoringMonitoring
 Initially q30–60 minsInitially q30–60 mins
 After stabilization q4hAfter stabilization q4h

63. Blood Product AdministrationBlood Product Administration
Red Blood CellsRed Blood Cells
Tissue hypoperfusion resolvedTissue hypoperfusion resolved
No extenuating circumstancesNo extenuating circumstances
 Coronary artery diseaseCoronary artery disease
 Acute hemorrhageAcute hemorrhage
 Lactic acidosisLactic acidosis
Transfuse < 7.0 g/dl to maintain 7.0-9.0 g/dLTransfuse < 7.0 g/dl to maintain 7.0-9.0 g/dL

64. Supportive careSupportive care
 Deep vein thrombosis prophylaxis.Deep vein thrombosis prophylaxis.
 Stress ulcer prophylaxis.Stress ulcer prophylaxis.
 Glucose control.Glucose control.
 Maintain a Plateau pressure of less thanMaintain a Plateau pressure of less than
equal to 30 cmH2O and low tidal volume 4-6equal to 30 cmH2O and low tidal volume 4-6
ml/kg of Predicted body weight forml/kg of Predicted body weight for
mechanically ventilated patientsmechanically ventilated patients ..

65. Consideration for limitation ofConsideration for limitation of
supportsupport
 Discuss advance care planning with patients andDiscuss advance care planning with patients and
families. Describe likely outcomes and setfamilies. Describe likely outcomes and set
realistic expectations.realistic expectations.
 Focus on early diagnosis, targeted management,Focus on early diagnosis, targeted management,
and standardization of the care process use SSGand standardization of the care process use SSG

66. •Even with the ‘best’ parameters it is
not always easy to make the right
decision.………

67. ConclusionsConclusions
 Sepsis is a disease of microcirculation.Sepsis is a disease of microcirculation.
 Oxygen DonOxygen Don’t Go’t Go
Where the Blood Won’t Flow- Optimise theWhere the Blood Won’t Flow- Optimise the
Macrocirculation first.Macrocirculation first.
 Monitoring microcirculation at bedside isMonitoring microcirculation at bedside is
difficult- Lactate/ SCVO2difficult- Lactate/ SCVO2
 Treatment –SS guidelinesTreatment –SS guidelines

68. Thank youThank you

69. Suspected infection
Blood cultures
SBP< 90 even after
20-30ml/kg fluid or
Lactate > 4mmol/l
Appropriate Empirical
Antibiotics with in 1 hr/
source control
CVPCVP
MAPMAP
Goal achievedGoal achieved
SCVO2SCVO2
< 8 Fluids NS, RL/ Colloid
8-12
>60-90mmHg
< 60-90
Vasopressors
Noradrenaline/dopamine
< 60-90
Vasopressors
Noradrenaline/dopamine
<70%
< 30 HCt-Packed cells
SCVO2< 70%
Inotrope
Dobutamine
< 30 HCt-Packed cells
SCVO2< 70%
Inotrope
Dobutamine
SCVO2 >70%
Decrease
Oxygen
consumption
Decrease
Oxygen
consumption

70. Michard F et al, Am J Respir Crit Care Med 1999; 159:935-9Michard F et al, Am J Respir Crit Care Med 1999; 159:935-9
Michard F et al, Am J Respir Crit Care Med 2000; 162:134-8Michard F et al, Am J Respir Crit Care Med 2000; 162:134-8
Pulse Pressure Variation (PPV)Pulse Pressure Variation (PPV)
• The arterial PP is directlyThe arterial PP is directly
proportional to the SVproportional to the SV
• The systolic BP may beThe systolic BP may be
influenced by changes in the pleuralinfluenced by changes in the pleural
pressurepressure
120120
mmHgmmHg
4040
PPPPmaxmax
PPPPminmin
PPPPmaxmax - PP- PPminmin
(PP(PPmaxmax + PP+ PPminmin)/2)/2
∆∆PP =PP =
ArterialArterial
PressurePressure

71. Stroke Volume Variation (SVV)Stroke Volume Variation (SVV)
(pulse-contour analysis by the PiCCO monitor)(pulse-contour analysis by the PiCCO monitor)
SV maxSV max
SV minSV min
SV meanSV mean
SV max + SV minSV max + SV min
SVmeanSVmean
SVV =SVV =
The difference between the maximal and minimal
SV values over a floating period of 7.5 seconds

72. Cellular Oxygen Delivery
(1) central
Cardiac
output
P
a
O
2
O2 content
PaO2
Hb
SaO2
Cardiac output
Preload
Afterload
contractility
= Oxygen
delivery

73. The questionThe question “Will my patient respond“Will my patient respond
to fluids?”to fluids?” cannot be accuratelycannot be accurately
answered by any ‘preload’ parameteranswered by any ‘preload’ parameter
Principles of Volume challenge
To test Starling’s law the fluid needs to be given quickly – the
faster it is given the less that is needed
It makes no sense to test “preload” responses over long
periods of time (eg Kumar et al 2004)
The type of fluid is not critical if given quickly enough
There needs to be a change in CVP to know that Starling’s
Law has been tested

74. ICU TreatmentICU Treatment
 During the first 6 hrs of resuscitation,During the first 6 hrs of resuscitation,
 Central venous pressure 8–12 mm HgCentral venous pressure 8–12 mm Hg
 Mean arterial pressure (MAP) more than equalMean arterial pressure (MAP) more than equal
to 65 mm Hgto 65 mm Hg
 Urine output more than equal to 0.5 mL/kg/hrUrine output more than equal to 0.5 mL/kg/hr
 Central venous (superior vena cava) or mixedCentral venous (superior vena cava) or mixed
venous oxygen saturation more than equal tovenous oxygen saturation more than equal to
70% or more than equal to 65%, respectively70% or more than equal to 65%, respectively

75. PRELOAD assessment-VolumePRELOAD assessment-Volume
 To look at CVP/ PAOPTo look at CVP/ PAOP
 Always CVP is in relation to COAlways CVP is in relation to CO
Volume
responsive
Volume
unresponsive
Add dopamine or dobutamine

76. Volume
SV
Decreased
contractility
Right atrial volume
–The actual value
of the CVP is
determined by the
interaction of
Cardiac function
and return
function
return function
cardiac
function

77. EGDTEGDT
Suspected infection
Blood cultures
Obtain two or more BCs
One or more BCs should be percutaneous
One BC from each vascular access
device in place more than equal to 48 hrs
Culture other sites as clinically indicated.
Other diagnostic/imaging as indicated
Appropriate Empirical
Antibiotics with in 1 hr/
source control
Host factors/ local antibiogram/ suspected site
Combination antibiotics/ right dose
SBP< 90 even after
20-30ml/kg fluid or
Lactate > 4mmol/l

78. -
ue
n-
g
n
c
y
t
es prophylactic platelet transfusionsare to patientswith sepsiswho arereceiv-
Vasopressors and inotropic choices for
managing sepsis1,4
I.V. vasopressors in order of initiation Add I.V. inotropic therapy
• norepinephrine
• epinephrine added to or substituted for
norepinephrine
• vasopressin added to norepinephrine to increase
MAP or decrease norepinephrine dose
• dopamine substituted for norepinephrine only in
patients with low risk for tachydysrhy thmias or
experiencing bradycardia
• don’t use low-dose dopamine to increase renal
perfusion
• use phenylephrine only if patient is experiencing se-
rious dysrhythmias known to have been caused by
norepinephrine, cardiac output is known to be high
and BP persistently low, or as salvage therapy when
combined inotrope/ vasopressor drugs and low-dose
vasopressin have failed to achieve MAP target
Dobutamine is suggested to
be administered or added
to vasopressor support
when patient shows signs
of myocardial dysfunction
as suggested by elevated
cardiac filling pressures and
low cardiac output, or ongo-
ing signs of hypoperfusion,
despite achieving adequate
intravascular volume and
adequate MAP.