FREWAN-Septic Shock in Newborns

8/13/2019 FREWAN-Septic Shock in Newborns

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IntroductionIntroduction

Septicemia is a state of microbial invasion Septicemia is a state of microbial invasion

from a portal of entry to blood stream whichfrom a portal of entry to blood stream whichcauses sign of illness *causes sign of illness *

Important changes in function of every organImportant changes in function of every organ

y yy y

B/P + PerfusionB/P + Perfusion

Septic shockSeptic shock

**By Schottmuller in 1914By Schottmuller in 1914


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DefinitionsDefinitions

Sepsis:Sepsis:

Systemic inflammatory response to aSystemic inflammatory response to a

documenteddocumented infection.infection.SIRS manifestations + at least 1 of inadequateSIRS manifestations + at least 1 of inadequate

1/ Alteration in mental state1/ Alteration in mental state

2/ Hypoxemia (PaO2 < 72 mmHg)2/ Hypoxemia (PaO2 < 72 mmHg)

3/ Elevated plasma lactate level3/ Elevated plasma lactate level

4/ Oliguria (


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DefinitionsDefinitionsSeptic shockSeptic shock

A subset of patient with severe sepsisA subset of patient with severe sepsis

resuscitation, along with presence of allresuscitation, along with presence of all

manifestations of inadequate organmanifestations of inadequate organ

function/perfusionfunction/perfusion


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CausesCauses

Immature immune defense system:Immature immune defense system:

Underlying major cause for sepsis & septic shock inUnderlying major cause for sepsis & septic shock inneonatesneonates

Any microorganism (Bacterial/ Viral/ Fungal)Any microorganism (Bacterial/ Viral/ Fungal)

Major:Major:

-- Staphylococcus AureusStaphylococcus Aureus-- GroupGroup bb--Hemolytic Strep.Hemolytic Strep.

-- Gram negative bacilli (EGram negative bacilli (E--coli)coli)


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PathophysiologyPathophysiology

Hemodynamics in neonatal septic shock haveHemodynamics in neonatal septic shock have

not been systematically studiednot been systematically studied

Warm shock =loss of vascular tone,Warm shock =loss of vascular tone, systemicsystemic

blood flow andblood flow and B/PB/P

Cold shock =Cold shock = vascular tone,vascular tone, systemic bloodsystemic bloodflow and eventuallyflow and eventuallyB/PB/P


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MediatorMediator--induced cellular injuryinduced cellular injury

Inflammatory mediators are key players inInflammatory mediators are key players in

pathogenesispathogenesis

gram + and gramgram + and gram -- bacteria induce abacteria induce a

variety of proinflammatory mediators,variety of proinflammatory mediators,

including cytokinesincluding cytokines sepsis and shocksepsis and shock


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MediatorMediator--induced cellular injuryinduced cellular injury(1) The bacterial cell wall components:(1) The bacterial cell wall components:

-- li o ol saccharide ramli o ol saccharide ram Li id ALi id A

moietymoiety

-- Peptidoglycan (gram + &gramPeptidoglycan (gram + &gram --))

-- Lipoteichoic acid (gram+)Lipoteichoic acid (gram+)


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-- ILIL--8 : Important regulator of neutrophil8 : Important regulator of neutrophilfunctionfunction

Contributes to lung injury &Contributes to lung injury &dysfunction of other organsdysfunction of other organs

-- Other cytokines: ILOther cytokines: IL--1010

InterferonInterferon--gammagammaILIL--1212GG--CSF and GMCSF and GM--CSFCSF


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Activation complement systemActivation complement system Clearance ofClearance of

infecting microorganisms + enhances tissue damageinfecting microorganisms + enhances tissue damage

, ,, ,

occurs via induction of nitric oxideoccurs via induction of nitric oxide

Neutrophils dual role:Neutrophils dual role:Defense against microorganismsDefense against microorganisms

Become toxic inflammatory mediatorsBecome toxic inflammatory mediators


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TypeType MediatorMediator ActivityActivity

CellularCellular

mediatorsmediators

LipopolysaccharidLipopolysaccharidee

Lipoteichoic acidLipoteichoic acid

PeptidoglycanPeptidoglycan

SuperantigensSuperantigens

EndotoxinEndotoxin

Activation of macrophages, neutrophils, platelets,Activation of macrophages, neutrophils, platelets,

and endothelium releases various cytokines andand endothelium releases various cytokines and

other mediatorsother mediators

CytokinesCytokines

Potent proinflammatory effectPotent proinflammatory effect

HumoralHumoral

mediatorsmediators

ILIL--1b1b

ILIL--88

ILIL--66

ILIL--1010

MIF &GMIF &G--CSFCSF

Nitric oxideNitric oxide

ComplementComplement

Acts as pyrogen, stimulates B and TActs as pyrogen, stimulates B and T

lymphocyte proliferation, inhibits cytokinelymphocyte proliferation, inhibits cytokine

production, induces immunosuppressionproduction, induces immunosuppression

Activation and degranulation of neutrophilsActivation and degranulation of neutrophils

Cytotoxic, augments vascular permeability,Cytotoxic, augments vascular permeability,

contributes to shockcontributes to shock

Involved in hemodynamic alterations of septicInvolved in hemodynamic alterations of septic

shockshock


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Abnormalities of coagulation and fibrinolysisAbnormalities of coagulation and fibrinolysishomeostasis in sepsishomeostasis in sepsis

(1) Inflammatory mediators(1) Inflammatory mediators direct injury todirect injury tovascular endotheliumvascular endothelium endothelial cellsendothelial cells

release tissue factor (TF)release tissue factor (TF)

Extrinsic coagulation cascade & production ofExtrinsic coagulation cascade & production ofthrombinthrombin

Intravascular clotsIntravascular clots


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Abnormalities of coagulation and fibrinolysisAbnormalities of coagulation and fibrinolysishomeostasis in sepsishomeostasis in sepsis

(2) Endotoxins(2) Endotoxins activity of fibrinolysisactivity of fibrinolysisinhibitors lasmino en activator inhibitor &inhibitors lasmino en activator inhibitor &

thrombin)thrombin)

Imbalance among inflammation, coagulation,Imbalance among inflammation, coagulation,and fibrinolysisand fibrinolysis Multiple organMultiple organdysfunction and deathdysfunction and death


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PathogenesisPathogenesis

Predominant hemodynamic feature of septic shockPredominant hemodynamic feature of septic shock

is arterial vasodilationis arterial vasodilation

Dependency of blood pressure on C.ODependency of blood pressure on C.O

So if insufficient compensation with rise in C.OSo if insufficient compensation with rise in C.O

Vasodilation result inVasodilation result in hypotensionhypotension


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Early: The rise in C.O is limited byEarly: The rise in C.O is limited by

hypovolemia and fall in preload because ofhypovolemia and fall in preload because of

cardiac filling pressurescardiac filling pressures

Later: Even though C.O elevatesLater: Even though C.O elevates

(Hyperdynamic phase of sepsis and shock),(Hyperdynamic phase of sepsis and shock),

performance of heartperformance of heart


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Maldistribution of blood flowMaldistribution of blood flow

Disparity between the uptake and oxygenDisparity between the uptake and oxygen

demand in the tissuesdemand in the tissues

Resultant defect in capacity to extract oxygenResultant defect in capacity to extract oxygen

locallylocally++

Elevated arterial blood lactate levelsElevated arterial blood lactate levels


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PathogenesisPathogenesisMultiorgan dysfunction syndromeMultiorgan dysfunction syndrome

Described as auto destructive process that permitsDescribed as auto destructive process that permitsextension of normal pathophysiologic response toextension of normal pathophysiologic response toinfection, resulting in multiple organ dysfunctioninfection, resulting in multiple organ dysfunctionsyndrome. Organ dysfunction or failure may be the firstsyndrome. Organ dysfunction or failure may be the first

clinical sign of sepsis, and no organ system is immune toclinical sign of sepsis, and no organ system is immune tothe consequences of the inflammatory excesses of sepsis.the consequences of the inflammatory excesses of sepsis.

-- HypoxiaHypoxia

-- Direct cytotoxicityDirect cytotoxicity-- ApoptosisApoptosis

-- ImmunosuppressionImmunosuppression

-- CoagulopathyCoagulopathy


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Diagnosis of circulatoryDiagnosis of circulatory

compromisecompromise

Gold standard for diagnosis of circulatoryGold standard for diagnosis of circulatory

compromisecompromise unknownunknownBlood pressureBlood pressure

Skin capillary refill timeSkin capillary refill time

CoreCore--peripheral temperature differenceperipheral temperature difference

Urine output and hyperkalemiaUrine output and hyperkalemiaAcidosisAcidosis


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Diagnosis of circulatory compromiseDiagnosis of circulatory compromise

Blood pressure:Blood pressure:

In preterm, mean B/P indicator valuesIn preterm, mean B/P indicator values

20 mmHg 40 mmHg20 mmHg 40 mmHg? In between? In between

Skin capillary refill time:Skin capillary refill time:

-- Traditionally acceptable < 3 secondsTraditionally acceptable < 3 seconds

-- Little relationship between Cap. Refill time andLittle relationship between Cap. Refill time andmeasures of systemic blood flowmeasures of systemic blood flow

-- Also in PT < 30 weeks only when > 5 secondsAlso in PT < 30 weeks only when > 5 seconds


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CoreCore--peripheral temperature difference:peripheral temperature difference:

In termIn term-- Little data to support accuracy ofLittle data to support accuracy of

corecore--peripheral temperature differenceperipheral temperature difference

In pretermIn preterm-- No relat onsh p ound betweenNo relat onsh p ound betweenthis measure and systemic blood flowthis measure and systemic blood flow

Low urine output & hyperkalemia:Low urine output & hyperkalemia:

Strong relationshipStrong relationship DelayDelay


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Lactic acid, PH, and base excess:Lactic acid, PH, and base excess:PH and BE: Little relationship with lowPH and BE: Little relationship with low

Lactic acid: No relationLactic acid: No relation

Organ blood flow:Organ blood flow:

Doppler velocity measurements (Small BVDoppler velocity measurements (Small BV

Limited )Limited )


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TreatmentTreatment

Treatment Strategy should relay on causativeTreatment Strategy should relay on causativefactors leading to cardiovascular compromise:factors leading to cardiovascular compromise:

1/ Inappropriate peripheral vasoregulation1/ Inappropriate peripheral vasoregulation

2/ Dysfunction of immature myocardium2/ Dysfunction of immature myocardium

Generally, absolute hypovolumia is a muchGenerally, absolute hypovolumia is a muchless frequent cause of neonatal hypotension,less frequent cause of neonatal hypotension,

especially in PT (regardless shock type)especially in PT (regardless shock type)


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TreatmentTreatment

(1)(1) Volume administrationVolume administration

Evidence that absolute hypovolumia isEvidence that absolute hypovolumia isuncommon cause of neonatal hypotension:uncommon cause of neonatal hypotension:

1.1.B/P usually associated with N / or evenB/P usually associated with N / or evenCOCO2. Dopamine better than volume adm in2. Dopamine better than volume adm in

normalizing B/Pnormalizing B/P


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TreatmentTreatment

(1)(1) Volume administrationVolume administration

3. Most important: Myocardial dysfunction3. Most important: Myocardial dysfunctionfrequently contributes to the development offrequently contributes to the development of

4. Aggressive volume administration, esp. in PT4. Aggressive volume administration, esp. in PT

is associated with higher pulmonary, CV, GIis associated with higher pulmonary, CV, GIand CNS morbidity & mortalityand CNS morbidity & mortality


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TreatmentTreatment

-- Therefore, esp. in PT, fluid resuscitationTherefore, esp. in PT, fluid resuscitation

should be minimizedshould be minimized

-- Another concern: Type of fluidAnother concern: Type of fluid

BestBest Isotonic saline 10Isotonic saline 10--20ml/kg20ml/kgButBut Unbalanced nature of N/SUnbalanced nature of N/S

I.e.: Its adm. in large amount over a short periodI.e.: Its adm. in large amount over a short periodof time may worsen metabolic acidosis !of time may worsen metabolic acidosis !


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TreatmentTreatment

(2)(2) Pharmacologic TherapyPharmacologic Therapy(A) Dopamine(A) Dopamine

-- Most commonly used Tx of hypotension in PTMost commonly used Tx of hypotension in PT-- DoseDose--dependent dopaminergic,dependent dopaminergic, . and. and ..

adrener ic and serotonin rece tor CVadrener ic and serotonin rece tor CV

stimulantstimulant-- Basically affects all 3 major determinants ofBasically affects all 3 major determinants of

CVS function mainly after load and MC effectCVS function mainly after load and MC effect

-- Dosage: 2 to 20 ug /kg/min (adult dataDosage: 2 to 20 ug /kg/min (adult data

pharmacodynamics)pharmacodynamics)


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TreatmentTreatment

(A) Dopamine(A) Dopamine

-- Severe illnessSevere illnessCV sensitivity to dopamineCV sensitivity to dopamine

so with disease advancement, larger doses mayso with disease advancement, larger doses may

be neededbe needed

i.e.: Dosage adm. should be tailored toi.e.: Dosage adm. should be tailored to

pharmacodynamic effect in pt. at bedsidepharmacodynamic effect in pt. at bedside

(rather than following conventional dose(rather than following conventional doserecommendations based on adult data)recommendations based on adult data)


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TreatmentTreatment

Practical TipPractical Tip

In Extreme PTIn Extreme PT

--11-- Weak relationship between BP and systemicWeak relationship between BP and systemic

blood flow (blood flow ( BP does not necessarilyBP does not necessarily

guarantee good tissue perfusion)guarantee good tissue perfusion)

--22-- Immature myocardium struggle to maintainImmature myocardium struggle to maintain

appropriate systemic blood flow againstappropriate systemic blood flow against

suddensudden in peripheral VRin peripheral VR


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TreatmentTreatment


So,So, dopamine doses willdopamine doses will after loadafter load improveimprove

BP but, without effective myocardial functionBP but, without effective myocardial functionimprovement, the systemic blood flow may notimprovement, the systemic blood flow may not

im rove and ma even worsenim rove and ma even worsen

So neonatologists must accept lower end BPSo neonatologists must accept lower end BP

values with Dopamine dosages below 10values with Dopamine dosages below 10ug/kg/min ( unless measures to monitor systemicug/kg/min ( unless measures to monitor systemic

blood flow are available)blood flow are available)


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TreatmentTreatment


Recommendation: Combination of DobutamineRecommendation: Combination of Dobutamineand lowand low-- medium dose of Dopamine to maintainmedium dose of Dopamine to maintain


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TreatmentTreatment

(3)(3) CorticosteroidsCorticosteroids

Evidence of benefit in vasopressor resistantEvidence of benefit in vasopressor resistant

hypotension:hypotension:

11-- Regulates the expression of CV adrenergicRegulates the expression of CV adrenergic

recep orsrecep ors reverse vasopressor res s ancereverse vasopressor res s ance

22-- Inhibit catecholamine metabolism and theInhibit catecholamine metabolism and the

production of vasoactive factors( nitric oxide)production of vasoactive factors( nitric oxide)

33-- Improve intracellular Calcium levelImprove intracellular Calcium level


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TreatmentTreatment

(3)(3) CorticosteroidsCorticosteroids

Concerns:Concerns:

11-- Potential short & long term side effectPotential short & long term side effect22 If adrenal function intactIf adrenal function intact Reactive toReactive to

I.e.: Steroids administration benefit mayI.e.: Steroids administration benefit may

become equivocal ( always analyze steroidsbecome equivocal ( always analyze steroidslevel prior to adm.)level prior to adm.)


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TreatmentTreatment

(4) Other :(4) Other :

-- Antibiotics !Antibiotics !-- Supportive measures:Supportive measures:

zz

calcium levelscalcium levels


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ConclusionConclusion

Hemodynamics in neonatal septic shock haveHemodynamics in neonatal septic shock havenot been systematically studiednot been systematically studied

None of the parameters used to diagnoseNone of the parameters used to diagnoseneonatal circulatory compromise has sufficientneonatal circulatory compromise has sufficientaccuracy to be used on its ownaccuracy to be used on its own


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Sustained stabilization of CV status withSustained stabilization of CV status with

rovision of a ro riate BP, CO, tissuerovision of a ro riate BP, CO, tissue

perfusion and oxygenation remains aperfusion and oxygenation remains adifficult task in most critically illdifficult task in most critically ill

hypotensive newbornshypotensive newborns

C l iC l i


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The addition of echocardiographic hemodynamicThe addition of echocardiographic hemodynamicassessment to BP monitoring to clinicalassessment to BP monitoring to clinical

evaluation of neonates are necessar to betterevaluation of neonates are necessar to better

understand changes in organ blood flow andunderstand changes in organ blood flow andtissue perfusiontissue perfusion


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ReferencesReferences

Cardiovascular Compromise In The Newborn Infant. AverysCardiovascular Compromise In The Newborn Infant. AverysDiseases of the newborn by Taeusch /Ballard /Gleason. 8thDiseases of the newborn by Taeusch /Ballard /Gleason. 8thedition Chapter 31edition Chapter 31

Towards The Early Diagnosis Of Neonatal Sepsis And SepsisTowards The Early Diagnosis Of Neonatal Sepsis And Sepsis--like Illness Using Novel Heart Rate Analysis. Pamela Griffin,like Illness Using Novel Heart Rate Analysis. Pamela Griffin,MD. Pediatrics VOL.107 No.1 January 2001, pp.97MD. Pediatrics VOL.107 No.1 January 2001, pp.97--104104

Septic Shock . Sat Sharma, MD, FRCPC, FACP, FCCP,Septic Shock . Sat Sharma, MD, FRCPC, FACP, FCCP,DABSM. Medline.DABSM. Medline.

Shock, Septic. Michael R filbin,MD. Medline.Shock, Septic. Michael R filbin,MD. Medline.

Heart Rate Characteristics In Neonatal Sepsis: A PromisingHeart Rate Characteristics In Neonatal Sepsis: A Promising

Test That Is Still Premature. Braham Goldstein. PediatricsTest That Is Still Premature. Braham Goldstein. Pediatrics2005;115:10702005;115:1070--10721072

Historical Perspectives: Group B Streptococcus In NeonatalHistorical Perspectives: Group B Streptococcus In NeonatalSepsis: Emergence As An Important Pathogen. Alistair G.SSepsis: Emergence As An Important Pathogen. Alistair G.S

Philip. Neoreviews 2004;5;ePhilip. Neoreviews 2004;5;e--467467--e470e470

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FREWAN-Septic Shock in Newborns