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

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Page 1: Sepsis guidelines 2015

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.

Page 2: Sepsis guidelines 2015

Case ScenarioCase Scenario 35 year old male patient brought to ICU with 3 35 year old male patient brought to ICU with 3

day old perforation, day old perforation, Posted for emergency Posted for emergency LapratomyLapratomy

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, Pulse 130/mt well felt, BP 80/60 mm Hg,

Restless,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 lac SC-2.0 INR 2.0, Platelets 1.2 lac Lactate 5.0Lactate 5.0

Is he in septic shock ?

Page 3: Sepsis guidelines 2015

Terminology and Terminology and DefinitionsDefinitions

Page 4: Sepsis guidelines 2015

Shock definition Shock definition Shock Shock is defined as a life-threatening, is defined as a life-threatening,

generalized generalized maldistributionmaldistribution of blood flow of blood flow resulting in failure to deliver and/or utilize resulting in failure to deliver and/or utilize adequate amounts of oxygen, leading to tissue adequate amounts of oxygen, leading to tissue dysoxia.dysoxia.

Hypotension [SBP Hypotension [SBP < < 90 mmHg, SBP decrease of 90 mmHg, SBP decrease of 40 mmHg from baseline, or mean arterial 40 mmHg from baseline, or mean arterial pressure (MAP) pressure (MAP) < < 65 mmHg], while commonly 65 mmHg], while commonly present, should present, should not be required to define shocknot be required to define shock. . Shock requires evidence of inadequate tissue Shock requires evidence of inadequate tissue perfusion on physical examinationperfusion on physical examination..

Page 5: Sepsis guidelines 2015

Relationship Of Infection, SIRS, Relationship Of Infection, SIRS, Sepsis Severe Sepsis and Septic Sepsis Severe Sepsis and Septic

ShockShock

SIRSINFECTION

PANCREATITIS

BURNS

TRAUMA

OTHER

SEPSIS

SEVERESEPSIS

SEPTICSHOCKBacteria

Fungus ParasitesVirus

Page 6: Sepsis guidelines 2015

Sepsis: Defining a Disease Continuum

A clinical response arising from a nonspecific insult, including 2 of the following:

•Temperature 38oC or 36oC •HR 90 beats/min•Respirations 20/min / PCo2 30 cms H2O•WBC count 12,000/mm3 or 4,000/mm3 or >10% immature neutrophils

SIRSSystemic Inflammatory Response Syndrome

SIRS with a presumed or confirmed infectious process

SepsisSepsisSIRSSIRSInfectionInfection Severe Severe SepsisSepsis

SEPTIC SHOCK

Inflammatory response to microorganisms or invasion of normally sterile tissues

Page 7: Sepsis guidelines 2015

SepsisSepsisSIRSSIRSInfection/Infection/TraumaTrauma

Severe Severe SepsisSepsis

Sepsis with 1 sign of organ failureCardiovascular ( hypotension)Lungs: early fall in arterial

PO2, (ARDS):Kidneys -oliguria, anuria,

azotemia, proteinuria SC more than 2

Liver TB more than 2Digestive tract- vomiting,

diarrhea and ileus Brain - confusion

SEPTICSEPTICShockShock

Hypotension despite adequate fluid resuscitation/Requiring vasopressors/Inotropes

Disease continuum

Page 8: Sepsis guidelines 2015

Arterial hypotensionTachycardia

Increased cardiac output/low SVR/high SvO2

Altered skin perfusionDecreased urine output

Hyperlactatemia – increased base deficit

Altered WBC countIncreased CRP,

IL-6, PCT concentrations

Rigor– fever(sometimes hypothermia)

Tachypnea/respiratory alkalosis

Positive fluid balance – edema

General signs & symptomsGeneral inflammatory reaction

Hemodynamic alterations

Signs of organ dysfunction

HypoxemiaCoagulation abnormalities

Altered mental status

Expanded signs of SIRS

Page 9: Sepsis guidelines 2015

Acute Organ DysfunctionAcute Organ DysfunctionTachycardiaHypotension

CVP PAOP

Jaundice Enzymes Albumin

PT

Altered Consciousness

ConfusionPsychosis

TachypneaPaO2 <70 mm Hg

SaO2 <90%PaO2/FiO2 300

OliguriaAnuria

Creatinine

Platelets PT/APTT Protein C D-dimer

Balk. Crit Care Clin 2000;16:337-52

Page 10: Sepsis guidelines 2015

Pathophysiology Pathophysiology

Page 11: Sepsis guidelines 2015

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

Page 12: Sepsis guidelines 2015

Pathogenisis of Pathogenisis of SepsisSepsis

TRIGGER INTERACTION WITH HUMAN CELLS

Coagu

lation

abno

rmalit

iesPro-inflammatory

Anti inflammatory

Endothelial injuryNitric oxide

over productionCardiac dysfunction

HypotensionMicro-emboli

Hypoperfusion Mitochondrial

dysfunction Organ injury MODS

Death

Primary mediators

Secondary mediators

Monocytes Macrophages

NeutophilsPlasma

Endothelial cells

Page 13: Sepsis guidelines 2015

Immune Response to Injury/ Immune Response to Injury/ InfectionInfectionInfection/injuryInfection/injury

Prompt coordinatedPrompt coordinatedprotectsprotects

Excessive, poor regulationExcessive, poor regulationharmsharms

Deficient, weakDeficient, weakInf establishedInf established

Immunologic Cascade1.1. Cytokine releaseCytokine release2.2. Activation of macrophage/ neutrophilsActivation of macrophage/ neutrophils3.3. Activation of neuro endocrine reflexActivation of neuro endocrine reflex4.4. Activation of plasma protein cascades Activation of plasma protein cascades

(Complement,Coagulation, fibrinolysis)(Complement,Coagulation, fibrinolysis)

Page 14: Sepsis guidelines 2015

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

Page 15: Sepsis guidelines 2015

Why different bacteria Why different bacteria stimulate different Effects ?stimulate 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.

ImmunosuppressedExtremes of age

Malnutrition Alcohol, Drug Abuse

MalignancyHIV/AIDS

Chronic Health Issues – Diabetes, Liver Failure, Heart

Disease, Corticosteroids, ChemotherapyMultiple invasive procedures

or invasive lines

Page 16: Sepsis guidelines 2015

Microcirculation Microcirculation

Page 17: Sepsis guidelines 2015

Key steps in oxygen Key steps in oxygen cascadecascade

Macrocirculation

Microcirculation

Page 18: Sepsis guidelines 2015

Why the microcirculation is important in Why 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.

Page 19: Sepsis guidelines 2015

Local

ShuntPrecapillary sphincter= vasodilatation/vasoconstriction

cell

= cellular utilization O2 in sepsis

Interstitial matrix= edema causes barrier to O2

delivery to the cell

Postcapillary venule

Microcirculatory defects

Page 20: Sepsis guidelines 2015

Spronk P, Zandstra D, Ince C (2004) Critical Care 8:462-468

Sepsis is a disease of the microcirculation

Page 21: Sepsis guidelines 2015

Microcirculation Microcirculation 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

Page 22: Sepsis guidelines 2015

Microcirculation Microcirculation 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.

Page 23: Sepsis guidelines 2015

Markers of Macro-Markers of Macro-circulation and Micro circulation and Micro

circulationcirculation

Resuscitation end Resuscitation end pointspoints

Page 24: Sepsis guidelines 2015
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Orthogonal polarizationspectral (OPS) imaging

Gastric Tonometry

Microdialysis

Sublingual capnometry

ScVO2Base deficitMediators

Page 26: Sepsis guidelines 2015

Microcirculation Microcirculation assessmentassessment

Tissue perfusionTissue perfusion Gastric tonometryGastric tonometry

Page 27: Sepsis guidelines 2015

Orthogonal polarizationOrthogonal polarizationspectral (OPS) imagingspectral (OPS) imaging

Page 28: Sepsis guidelines 2015

Capillary flow in sepsisCapillary flow in sepsis

Page 29: Sepsis guidelines 2015

Understanding oxygen Understanding oxygen delivery to cellular leveldelivery to cellular level

Page 30: Sepsis guidelines 2015

Matching delivery Matching delivery

== Requirement

Assessment of OxygenationO2 delivery is a Cardio-Respiratory function

Page 31: Sepsis guidelines 2015

DODO22/VO/VO2 2 Oxygen delivery vs Oxygen delivery vs RequirementRequirement

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 failureShunting due to micro-emboli

Page 32: Sepsis guidelines 2015

OO22

COCO22

AlveoliPAO2

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

=

Page 33: Sepsis guidelines 2015

Volume Vesseltone

Heart function

If shock is prolonged, mechanisms of shock are combined

Physiologic Classification of Physiologic Classification of Acute Circulatory InsufficiencyAcute Circulatory Insufficiency

Fluids / blood Vasopressors Inotropes

Page 34: Sepsis guidelines 2015

TIME TIME isis

TISSUETISSUE

Oxygen DonOxygen Don’’t Go t Go Where the Blood WonWhere the Blood Won’’t t FlowFlow!!

From these two statements three things are obviousEarly therapy before mitochondria gets damaged.

Macro circulation should be optimised first.Micro circulation optimisation to prevent

Mitochondrial injury is the target

Page 35: Sepsis guidelines 2015

Sepsis Management Sepsis Management BundleBundle

Macrocirculation Macrocirculation optimization to correct optimization to correct

MicrocirculationMicrocirculation

Page 36: Sepsis guidelines 2015

Sepsis Management Sepsis Management BundleBundle

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

Page 37: Sepsis guidelines 2015

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.

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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.

Page 39: Sepsis guidelines 2015

DOCUMENT REASSESSMENT OF DOCUMENT REASSESSMENT OF VOLUME STATUS AND TISSUE VOLUME STATUS AND TISSUE

PERFUSION WITHPERFUSION WITHEITHEREITHERRepeat focused exam (after initial fluid Repeat focused exam (after initial fluid resuscitation) by licensed independent practitioner resuscitation) by licensed independent practitioner including vital signs, cardiopulmonary, capillary including vital signs, cardiopulmonary, capillary refill, pulse, and skin findings.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 ultrasoundDynamic assessment of fluid responsiveness with Dynamic assessment of fluid responsiveness with passive leg raise or fluid challengepassive leg raise or fluid challenge

Of note, the 6-hour bundle has been updated; The 3-hour SSC bundle is not affected.

Page 40: Sepsis guidelines 2015

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 least Collect at least 2 sets of aerobic and anaerobic blood 2 sets of aerobic and anaerobic blood culturescultures; these should be drawn ; these should be drawn before giving antibioticsbefore giving antibiotics -- -- as long as cultures can be collected without delaying as long as cultures can be collected without delaying antimicrobial therapy by antimicrobial therapy by >45 minutes>45 minutes..

At least one blood culture bottle set should be collected At least one blood culture bottle set should be collected percutaneouslypercutaneously (through a needle stick), and one drawn (through a needle stick), and one drawn from from 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 be If 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 of indicated, with the same imperative to avoid undue delay of antibiotics.antibiotics.

Page 41: Sepsis guidelines 2015

DiagnosisDiagnosis In the uncommon situation in which invasive In the uncommon situation in which invasive

candidiasis is being considered as a cause of candidiasis is being considered as a cause of sepsis, collect blood for the sepsis, collect blood for the 1,3 beta-D-1,3 beta-D-glucan assayglucan assay, and/or the , and/or the mannan and mannan and anti-mannan antibody assaysanti-mannan antibody assays, which can , which can help diagnose invasive candida infections.help diagnose invasive candida infections.

Appropriate Appropriate imaging studiesimaging studies be be performed quickly, to help confirm potential performed quickly, to help confirm potential sources of infection. sources of infection.

Page 42: Sepsis guidelines 2015

Source ControlSource Control Evaluate patient for a focused Evaluate patient for a focused

infection amendable to source infection amendable to source control measures including control measures including abscess drainage or tissue abscess drainage or tissue debridement.debridement.• Move rapidlyMove rapidly• Consider physiologic upset of Consider physiologic upset of

measuremeasure• Intravascular access devicesIntravascular access devices

Page 43: Sepsis guidelines 2015

Antibiotic TherapyAntibiotic Therapy Begin intravenous antibiotics Begin intravenous antibiotics

within first hour of recognition within first hour of recognition of severe sepsis.of severe sepsis.

Page 44: Sepsis guidelines 2015

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

Page 45: Sepsis guidelines 2015

Antibiotics

Always look at you

local organisms and resistance patterns

Page 46: Sepsis guidelines 2015

Antibiotic TherapyAntibiotic TherapyReassess antimicrobial Reassess antimicrobial regimen at 48-72 hrsregimen at 48-72 hrs• Microbiologic and clinical Microbiologic and clinical

datadata• Narrow-spectrum antibioticsNarrow-spectrum antibiotics• Non-infectious cause Non-infectious cause

identifiedidentified• Prevent resistance, reduce Prevent resistance, reduce

toxicity, reduce coststoxicity, reduce costs

Page 47: Sepsis guidelines 2015

Fluid therapyFluid therapyInitial fluid challenge in sepsis-Initial fluid challenge in sepsis-

induced tissueinduced tissuehypoperfusion (hypotension or hypoperfusion (hypotension or

elevated lactate)elevated lactate)

A minimum of 30ml/kg of crystalloids A minimum of 30ml/kg of crystalloids (a portion of this may be albumin (a portion of this may be albumin

equivalent)equivalent)

Page 48: Sepsis guidelines 2015

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 3- Patients in the ICU, already resuscitated for several hours or dayshours 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

Page 49: Sepsis guidelines 2015

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?

Prediction Prediction 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 edema with potential risks of pulmonary edema and/or excessive cumulative fluid balanceand/or excessive cumulative fluid balance

Page 50: Sepsis guidelines 2015

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

Page 51: Sepsis guidelines 2015
Page 52: Sepsis guidelines 2015

Fluid challengeFluid challenge 250ml or 3ml/kg over 5 to 10 250ml or 3ml/kg over 5 to 10

minutesminutes 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

Page 53: Sepsis guidelines 2015

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 preload Increase in right ventricular preload (Thomas et al 1965)

Increase in left ventricular preload Increase in left ventricular preload (Rocha 1987, Takagi 1989, De Hert 1999, Kyriades 1994 )

Transient effect Transient effect (Gaffney 1982)(Gaffney 1982)

PLR could be used as a test to detect volume responsiveness PLR could be used as a test to detect volume responsiveness rather than as a therapyrather than as a therapy

Page 54: Sepsis guidelines 2015

Parameters to guide fluid Parameters to guide fluid administrationadministration

Page 55: Sepsis guidelines 2015
Page 56: Sepsis guidelines 2015

Vasopressors / InotropesVasopressors / Inotropes

. .

Page 57: Sepsis guidelines 2015

Vasopressors Vasopressors VasopressorsVasopressors should be begun initially to target a mean should be begun initially to target a mean

arterial pressure of 65 mm Hg (arterial pressure of 65 mm Hg (Grade 1CGrade 1C).). An An arterial catheterarterial catheter for hemodynamic monitoring should for hemodynamic monitoring should

be placed as soon as practical, if resources are available, for be placed as soon as practical, if resources are available, for all patients requiring vasopressors (ungraded all patients requiring vasopressors (ungraded recommendation).recommendation).

NorepinephrineNorepinephrine (Levophed) should be provided as the first- (Levophed) should be provided as the first-line vasopressor (line vasopressor (Grade 1BGrade 1B).).

EpinephrineEpinephrine is considered the next-line agent for septic is considered the next-line agent for septic shock after norepinephrine in the Surviving Sepsis shock after norepinephrine in the Surviving Sepsis Guidelines. When norepinephrine is insufficient to maintain Guidelines. When norepinephrine is insufficient to maintain MAP 65 mm Hg, epinephrine should be added to or MAP 65 mm Hg, epinephrine should be added to or substituted for norepinephrine (substituted for norepinephrine (Grade 2BGrade 2B))..

Page 58: Sepsis guidelines 2015

VasopressinVasopressin VasopressinVasopressin at 0.03 units/minute is appropriate to at 0.03 units/minute is appropriate to

use with norephinephrine, either to improve use with norephinephrine, either to improve perfusion (increase MAP) or to reduce the required perfusion (increase MAP) or to reduce the required dose of norepinephrine (ungraded recommendation).dose of norepinephrine (ungraded recommendation).

Vasopressin is not recommended for use as a single Vasopressin is not recommended for use as a single vasopressor for septic shock (ungraded vasopressor for septic shock (ungraded recommendation).recommendation).

Vasopressin doses higher than 0.03 - 0.04 units/min Vasopressin doses higher than 0.03 - 0.04 units/min are recommended to be reserved only for dire are recommended to be reserved only for dire situations of septic shock refractory to standard situations of septic shock refractory to standard doses of multiple vasopressors (ungraded doses of multiple vasopressors (ungraded recommendation).recommendation).

Page 59: Sepsis guidelines 2015

Dobutamine Dobutamine DobutamineDobutamine should be tried for patients in septic shock should be tried for patients in septic shock

who have low cardiac output with high filling pressures who have low cardiac output with high filling pressures while on vasopressors, or who have persistent evidence of while on vasopressors, or who have persistent evidence of hypoperfusion after attaining an adequate mean arterial hypoperfusion after attaining an adequate mean arterial pressure and intravascular volume (with or without pressure and intravascular volume (with or without vasopressors).vasopressors).

A dobutamine infusion up to 20 mcg/kg/min can be added A dobutamine infusion up to 20 mcg/kg/min can be added to any vasopressor(s) in use. Dobutamine is also an to any vasopressor(s) in use. Dobutamine is also an appropriate first-line agent in patients with severe sepsis appropriate first-line agent in patients with severe sepsis and low cardiac output, with a preserved mean arterial and low cardiac output, with a preserved mean arterial pressure (i.e., who are not in septic shock).pressure (i.e., who are not in septic shock).

Dobutamine is recommended Dobutamine is recommended notnot to be used to deliberately to be used to deliberately raise cardiac output to higher than normal levels in an raise cardiac output to higher than normal levels in an attempt to improve perfusion.attempt to improve perfusion.

Page 60: Sepsis guidelines 2015

DopamineDopamine DopamineDopamine is suggested to is suggested to not not be used as an alternative to be used as an alternative to

norepinephrine in septic shock, except in highly selected norepinephrine in septic shock, except in highly selected patients such as those with inappropriately low heart rates patients 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 be used tachyarrhythmias. Dopamine is recommended to not be used in low doses in a so-called renal-protective strategy.in low doses in a so-called renal-protective strategy.

PhenylephrinePhenylephrine is recommended to not be used for septic is recommended to not be used for septic shock, except when 1) septic shock persists despite the use shock, 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, or dose vasopressin; 2) cardiac output is known to be high, or 3) norepinephrine is considered to have already caused 3) norepinephrine is considered to have already caused serious arrhythmias.serious arrhythmias.

Page 61: Sepsis guidelines 2015

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 is ACTH stimulation test is notnot recommended.recommended.

Steroid therapy may be weaned once Steroid therapy may be weaned once vasopressors are no longer required.vasopressors are no longer required.

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Glucose ControlGlucose Control After initial stabilizationAfter initial stabilization

Glucose < 180 mg/dLGlucose < 180 mg/dL Continuous infusion insulin and Continuous infusion insulin and

glucose or feeding (enteral glucose or feeding (enteral preferred)preferred)

MonitoringMonitoring Initially q30–60 minsInitially q30–60 mins After stabilization q4hAfter stabilization q4h

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Blood Product Blood Product AdministrationAdministrationRed Blood CellsRed Blood Cells

Tissue hypoperfusion resolvedTissue hypoperfusion resolvedNo extenuating circumstancesNo extenuating circumstances

Coronary artery diseaseCoronary artery disease Acute hemorrhageAcute hemorrhage Lactic acidosisLactic acidosis

Transfuse < 7.0 g/dl to maintain 7.0-Transfuse < 7.0 g/dl to maintain 7.0-9.0 g/dL9.0 g/dL

Page 64: Sepsis guidelines 2015

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 Maintain a Plateau pressure of

less than equal to 30 cmH2O and less than equal to 30 cmH2O and low tidal volume 4-6 ml/kg of low tidal volume 4-6 ml/kg of Predicted body weight for Predicted body weight for mechanically ventilated patientsmechanically ventilated patients . .

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Consideration for limitation Consideration for limitation of supportof support

Discuss advance care planning with Discuss advance care planning with patients and families. Describe likely patients and families. Describe likely outcomes and set realistic outcomes and set realistic expectations.expectations.

Focus on early diagnosis, targeted Focus on early diagnosis, targeted management, and standardization of management, and standardization of the care process use SSGthe care process use SSG

Page 66: Sepsis guidelines 2015

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

Page 67: Sepsis guidelines 2015

Conclusions Conclusions Sepsis is a disease of Sepsis is a disease of

microcirculation. microcirculation. Oxygen DonOxygen Don’’t Go t Go

Where the Blood WonWhere the Blood Won’’t Flow- t Flow- Optimise the Macrocirculation Optimise the Macrocirculation first.first.

Monitoring microcirculation at Monitoring microcirculation at bedside is difficult- Lactate/ SCVO2 bedside is difficult- Lactate/ SCVO2

Treatment –SS guidelinesTreatment –SS guidelines

Page 68: Sepsis guidelines 2015

Thank you

Page 69: Sepsis guidelines 2015

Suspected infectionBlood cultures

SBP< 90 even after20-30ml/kg fluid or Lactate > 4mmol/l

Appropriate Empirical Antibiotics with in 1 hr/

source control

CVP

MAP

Goal achieved

SCVO2

< 8 Fluids NS, RL/ Colloid

8-12

>60-90mmHg

< 60-90Vasopressors

Noradrenaline/dopamine

<70%

< 30 HCt-Packed cellsSCVO2< 70%

InotropeDobutamine

SCVO2 >70%

DecreaseOxygen

consumption

Page 70: Sepsis guidelines 2015

Michard F et al, Am J Respir Crit Care Med 1999; 159:935-Michard F et al, Am J Respir Crit Care Med 1999; 159:935-99

Michard F et al, Am J Respir Crit Care Med 2000; 162:134-Michard F et al, Am J Respir Crit Care Med 2000; 162:134-88

Pulse Pressure Variation Pulse Pressure Variation (PPV)(PPV)

• The arterial PP is The arterial PP is directly proportional to directly proportional to the SVthe SV• The systolic BP may be The systolic BP may be influenced by changes in influenced by changes in the pleural pressure the pleural pressure 120 120

mmHgmmHg

4040

PPPPmaxmax

PPPPminmin

PPPPmaxmax - PP - PPminmin

(PP(PPmax max + PP+ PPminmin)/2)/2∆∆PP =PP =

Arterial Arterial Pressure Pressure

Page 71: Sepsis guidelines 2015

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

SVmeanSVmeanSVV =SVV =

The difference between the maximal and minimal SV values over a floating period of 7.5 seconds

Page 72: Sepsis guidelines 2015

Cellular Oxygen Delivery

(1) central

Cardiacoutput

PaO2

O2 contentPaO2

HbSaO2

Cardiac outputPreloadAfterloadcontractility

= Oxygendelivery

Page 73: Sepsis guidelines 2015

The questionThe question ““Will my patient respond Will my patient respond to fluids?to fluids?”” cannot be accurately cannot be accurately

answered by any answered by any ‘‘preloadpreload’’ parameter parameterPrinciples 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

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ICU Treatment ICU 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 Mean arterial pressure (MAP) more than

equal to 65 mm Hgequal to 65 mm Hg Urine output more than equal to 0.5 Urine output more than equal to 0.5

mL/kg/hrmL/kg/hr Central venous (superior vena cava) or Central venous (superior vena cava) or

mixed venous oxygen saturation more than mixed venous oxygen saturation more than equal to 70% or more than equal to 65%, equal to 70% or more than equal to 65%, respectively respectively

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PRELOAD assessment-PRELOAD assessment-Volume 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

Page 76: Sepsis guidelines 2015

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

Page 77: Sepsis guidelines 2015

EGDTEGDTSuspected infection

Blood cultures

Obtain two or more BCsOne or more BCs should be percutaneous

One BC from each vascular access device in place more than equal to 48 hrsCulture other sites as clinically indicated.

Other diagnostic/imaging as indicated

Appropriate Empirical Antibiotics with in 1 hr/

source controlHost factors/ local antibiogram/ suspected site

Combination antibiotics/ right dose

SBP< 90 even after20-30ml/kg fluid or Lactate > 4mmol/l

Page 78: Sepsis guidelines 2015