leanna r. miller, rn, mn, ccrn-cmc, pccn-csc, cen, cnrn, np education specialist lrm consulting
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Critical Care Immunology. Leanna R. Miller, RN, MN, CCRN-CMC, PCCN-CSC, CEN, CNRN, NP Education Specialist LRM Consulting Nashville, TN. Critical Care Immunology. Learning Outcomes - PowerPoint PPT PresentationTRANSCRIPT
Leanna R. Miller, RN, MN, CCRN-CMC, PCCN-CSC, CEN, CNRN, NPEducation Specialist
LRM ConsultingNashville, [email protected]
Learning OutcomesLearning OutcomesAnalyze the mediators (cytokines) Analyze the mediators (cytokines)
responsible for cellular and clinical responsible for cellular and clinical changes during the inflammatory response.changes during the inflammatory response.
Correlate the clinical significance of Correlate the clinical significance of immunoparalysis to trauma, sepsis and immunoparalysis to trauma, sepsis and open heart surgery.open heart surgery.
Evaluate strategies used to manage Evaluate strategies used to manage patients with immunoparalysis.patients with immunoparalysis.
recovery from critical illness requires proper immunologic balance between pro- and anti-inflammatory forces
persistence of a marked compensatory anti-inflammatory innate immune response following an insult such as sepsis, surgery, or trauma is termed immunoparalysis
an acquired immunodeficiency can be quantified through the measurement of: monocyte cell-surface HLA-DR
expressionanalysis of the capacity of whole
blood to produce TNFα upon ex vivo stimulation with endotoxin
during critical illness, there is a systemic anti-inflammatory state intended to avoid the spread of the local proinflammatory response
resulting immunosuppression increases the risk of nosocomial infectionsrelated to an increase in morbidity
and mortality in critically ill patients
Host Defenses Host Defenses exposed to injury & exposed to injury &
infectioninfectiondefense mechanismsdefense mechanisms
inflammationinflammationthrombosisthrombosishealinghealing
Stages of InflammationStages of Inflammationdestruction & removaldestruction & removalcontainmentcontainmentstimulation & amplification stimulation & amplification
of the immune responseof the immune responsepromotion of healingpromotion of healing
Innate - Cellular Adaptive - Cellular
PhagocytosisMonocytesNeutrophils
Dendritic Cells
Antibody ProductionB cells / Plasma cells
Antigen PresentationMonocytes
Dendritic Cells
Cytotoxic KillingCD8 T cells
Cytotoxic KillingNatural Killer Cells
Neutrophils
Cytokine & Chemokine ProductionCD4 T cells
Cytokine & Chemokine ProductionAll of the above
Innate - Noncellular Elements Adaptive – Noncellular Elements
CytokinesChemokinesComplement
ImmunoglobulinsCytokinesChemokines
Nonspecific ImmunityNonspecific Immunitynatural killer cells (NK)natural killer cells (NK)
kill viruses, bacteria, kill viruses, bacteria, neoplastic cellsneoplastic cells
regulate production of regulate production of erythrocytes & erythrocytes & granulocytesgranulocytes
ComplementComplementactivated by:activated by:
antigen/antibody complexantigen/antibody complextissue injurytissue injurytissue ischemiatissue ischemiacoagulationcoagulation
ComplementComplementactivated by:activated by:
cell debriscell debriskininskininsendotoxinendotoxinbacterial cell debrisbacterial cell debris
ComplementComplementopsonizationopsonizationmediator releasemediator release
histaminehistamineleukotrienesleukotrienes
CoagulationCoagulationactivated by:activated by:
Intrinsic pathwayIntrinsic pathwayExtrinsic pathwayExtrinsic pathway
CoagulationCoagulationexcessive intravascular excessive intravascular
coagulation leads to:coagulation leads to:vascular damagevascular damagetissue ischemiatissue ischemia
FibrinolysisFibrinolysisHemorrhage leads to:Hemorrhage leads to:
decreased Odecreased O22 delivery deliverytissue ischemiatissue ischemia
Tumor Necrosis FactorTumor Necrosis Factorfeverfeverendothelial damageendothelial damageanorexiaanorexiaprocoagulant activityprocoagulant activity responsiveness to responsiveness to
catecholaminecatecholamine
Triggers to IIRTriggers to IIRinfectioninfectionhypoperfusionhypoperfusionhypoxemiahypoxemiainjuryinjury
Endothelium
Neutrophil
Monocyte
IL-6IL-1TNF-
IL-6
Inflammatory Responseto Infection
Thrombotic Responseto Infection
Fibrinolytic Responseto Infection
TAFI
PAI-1
Suppressedfibrinolysis
Factor VIIIaTissue Factor
COAGULATION CASCADE
Factor Va
THROMBIN
Fibrin
Fibrin clotTissue Factor
Activation of the Immune Response
PathophysiologyPathophysiologyrole of initial insult in role of initial insult in
promoting promoting INFECTIONINFECTIONImmunosuppressionImmunosuppression
downregulationdownregulationblood productsblood products
stress responsestress responsehypercatabolism hypercatabolism
PathophysiologyPathophysiologyTransluminal migrationTransluminal migration
SIRSSIRSnosocomial nosocomial pneumoniapneumonia
PathophysiologyPathophysiologyFlow dependent OFlow dependent O22
consumptionconsumptionDODO22 > 600 > 600
VOVO22 > 150 > 150
PathophysiologyPathophysiologytissue ischemia and tissue ischemia and
reperfusionreperfusionxanthine oxidase xanthine oxidase
OO22 free radicals free radicals (ROS) (ROS) tissue tissue injuryinjury
Mortality ratesMortality ratesOne organ = 1%One organ = 1%Two organs = 11%Two organs = 11%Three organs = 50%Three organs = 50%Four organs = 75%Four organs = 75%
Nurse’s Role in Treatmentassessing system failureearly identificationminimizing complications
SIRS Criteria SIRS Criteria (2 or more)(2 or more)
Temperature > 38 Temperature > 38 °C or °C or < 36 °C< 36 °C
Heart rate > 90 beatsHeart rate > 90 beatsRR > 20 or paCORR > 20 or paCO22 < 32 < 32WBC > 12,000 or < 4,000 WBC > 12,000 or < 4,000
or > 10% bandsor > 10% bands
Levy et al. 2001 International Sepsis Definitions [email protected]
SIRS???
DefinitionsSIRSSIRS + Infection = SepsisSepsis + Acute Organ Dysfunction or hypoperfusion = Severe Sepsis
Severe Sepsis + CV failure = Septic Shock
Most common sites Most common sites of originof originUrinary tractUrinary tractGI systemGI systemRespiratory tractRespiratory tractSkin & woundsSkin & wounds
Predisposing FactorsPredisposing Factorsextremes in ageextremes in agegranulocytopeniagranulocytopeniaprior antibiotic useprior antibiotic usesevere burn, trauma, surgerysevere burn, trauma, surgeryfunctional aspleniafunctional asplenia
Predisposing FactorsPredisposing Factorsimmunosuppressionimmunosuppressionmalnutrition & TPNmalnutrition & TPNalcohol & drug abusealcohol & drug abuseprolonged ICU stayprolonged ICU stay
Assessing Acute Immune Assessing Acute Immune Inflammatory ResponseInflammatory ResponseProcalcitonin (PCT)Procalcitonin (PCT) 0.12 – 0.26 0.12 – 0.26
ng/mLng/mL
C – reactive protein (CRP) C – reactive protein (CRP) 0 – 5 0 – 5 mg/Lmg/L
IL – 6IL – 6 0 – 28 pg/mL0 – 28 pg/mL
Hermann et al;(2000) Procalcitonin in septic shock. Clin Chem Lab Med 38(1):41 - [email protected]
11stst Six Hours Six HoursResuscitation =
Cultures + Antibiotics + Early Goal – Directed Therapy
11stst Six Hours Six Hours Delays in management of the Delays in management of the
SIR result in higher mortality SIR result in higher mortality rates and increased utilization rates and increased utilization of hospital resourcesof hospital resources
Transition from Sepsis to Transition from Sepsis to Severe SepsisSevere Sepsis
occurs most often during the occurs most often during the 11stst 24 hours of hospitalization 24 hours of hospitalization
increase in mortality of 20 – increase in mortality of 20 – 46%46%
TransitionTransition tissue Otissue O22 delivery & CV delivery & CV
insufficiency accompanies insufficiency accompanies transitiontransition
usually not detected by VS usually not detected by VS nor SIRS criterianor SIRS criteria
OO22 Transport & Utilization Transport & Utilization
OO22 delivery is insufficient to delivery is insufficient to meet Omeet O22 demands @ cell level demands @ cell level
results in increased lactate results in increased lactate levelslevels
OO22 Transport & Utilization Transport & Utilization SvOSvO22 < 65% or ScvO < 65% or ScvO22 < 70% < 70%
result in increased lactate and result in increased lactate and suggest the presence of suggest the presence of global tissue hypoxia – global tissue hypoxia – greater extraction by tissuesgreater extraction by tissues
OO22 Transport & Utilization Transport & Utilization high SvOhigh SvO22, ScvO, ScvO22 & lactate & lactate
indicates that despite indicates that despite adequate global systemic Oadequate global systemic O22 delivery, the tissues are delivery, the tissues are unable to extract the Ounable to extract the O22
Identification of High Risk PatientIdentification of High Risk Patient single lactate > 4.0 or more at initial single lactate > 4.0 or more at initial
presentationpresentation failure to clear lactate levels during failure to clear lactate levels during
the 1the 1stst 6 hours is associated with 6 hours is associated with increased morbidity and mortalityincreased morbidity and mortality
Management of IIRManagement of IIRInitial ResuscitationInitial Resuscitation
EndpointsEndpointsCVP 8 to 12 mm HgCVP 8 to 12 mm HgMAP > 65 mm HgMAP > 65 mm HgUO > 0.5 mL/kg/hrUO > 0.5 mL/kg/hrSvOSvO22 > 70% > 70%
Management of IIRManagement of IIREarly antimicrobial therapyEarly antimicrobial therapy
empiric antibiotics within empiric antibiotics within 4 to 8 hours of hospital 4 to 8 hours of hospital presentationpresentation
Surviving Sepsis Surviving Sepsis Campaign recommends Campaign recommends antibiotics within 1 hourantibiotics within 1 hour
Management of IIRManagement of IIRsource of infection & local source of infection & local
hospital sensitivity & hospital sensitivity & resistance patternsresistance patterns
surgical consultationsurgical consultationresistant organisms when resistant organisms when
patients live in nursing homes patients live in nursing homes or are IV drug usersor are IV drug users
Volume TherapyVolume Therapy repletion of intravascular volumerepletion of intravascular volume rapid, 20 mL/kg boluses of either rapid, 20 mL/kg boluses of either
crystalloid or colloidcrystalloid or colloid CVP 8 – 12 mm HgCVP 8 – 12 mm Hg
Volume TherapyVolume Therapy 4% albumin or NS4% albumin or NS found no significant difference in found no significant difference in
mortality between the groupmortality between the group
Vasoactive AgentsVasoactive Agents Norepinephrine 2 – 20 Norepinephrine 2 – 20 g/ming/min Vasopressin 0.01 – 0.04 units/min – Vasopressin 0.01 – 0.04 units/min –
(VASST study)(VASST study) Phenylephrine 40 – 300 Phenylephrine 40 – 300 g/ming/min Dopamine 5 – 20 Dopamine 5 – 20 g/kg/ming/kg/min
Vasoactive AgentsVasoactive Agents Adverse consequencesAdverse consequences
splanchnic hypoperfusionsplanchnic hypoperfusionexcess tachycardiaexcess tachycardiacoronary ischemia coronary ischemia
RBC ReplacementRBC Replacement If ScvOIf ScvO22 remains < 70% after remains < 70% after
optimization of preload, afterload optimization of preload, afterload and arterial Oand arterial O22 saturation saturation increase Hct to 30%increase Hct to 30%optimal erythrocyte transfusionoptimal erythrocyte transfusionfresh vs. stored bloodfresh vs. stored [email protected]
Inotropic TherapyInotropic Therapy Sepsis may be accompanied by myocardial Sepsis may be accompanied by myocardial
suppression in 10 – 15% of patientssuppression in 10 – 15% of patients dobutamine titrated at 2.5 dobutamine titrated at 2.5 g/kg/min g/kg/min
every 20 – 30 minutes to ScvOevery 20 – 30 minutes to ScvO22 of 70% of 70%milrinone (long half – life and accumulates milrinone (long half – life and accumulates
in renal failure)in renal failure) [email protected]
Decreasing ODecreasing O22 consumption consumption intubation, sedation, analgesiaintubation, sedation, analgesia control fevercontrol fever
Administration of steroids, has theoretical benefits in the setting
of severe sepsis by inhibitingthe massive inflammatory
cascade
Administration of steroids, has theoretical benefits in the setting
of severe sepsis by inhibitingthe massive inflammatory
cascade
Steroid TherapySteroid Therapy Inflammatory cascade leads to (RAI): Inflammatory cascade leads to (RAI):
inadequate release or response to inadequate release or response to ACTHACTH
peripheral steroid resistance @ peripheral steroid resistance @ receptor levelreceptor level
Steroid TherapySteroid Therapy If on vasopressors, draw random cortisol If on vasopressors, draw random cortisol
level; if < 25 mcg/mL give corticosteroids level; if < 25 mcg/mL give corticosteroids If not on vasopressor, draw baseline If not on vasopressor, draw baseline
random cortisol level, do cort stim test; random cortisol level, do cort stim test; get levels @ 30 & 60 min – if difference is get levels @ 30 & 60 min – if difference is < 9 < 9 give steroids give steroids
Steroid TherapySteroid Therapy low doses of hydrocortisone decreased low doses of hydrocortisone decreased
requirement for vasopressors and lowered requirement for vasopressors and lowered mortalitymortality Hydrocortisone 50 mg IV every 6 hoursHydrocortisone 50 mg IV every 6 hours Dexamethasone 4 mg IV every 8 hoursDexamethasone 4 mg IV every 8 hours Fludrocortisone 100 Fludrocortisone 100 g PFT every dayg PFT every day
Protective Lung StrategiesProtective Lung Strategies 6 mL/kg vs. 12 mL/kg6 mL/kg vs. 12 mL/kg
9.9% absolute 28 – day mortality 9.9% absolute 28 – day mortality in low TV groupin low TV group
Tight Glycemic ControlTight Glycemic Control 100 – 150 mg/dL100 – 150 mg/dL
8.0% reduction in mortality8.0% reduction in mortality
High – volume HemofiltrationHigh – volume Hemofiltration removal of inflammatory cytokinesremoval of inflammatory cytokines
CVVH for Treatmentlow-volume CVVH (20 mL/kg BW), filters changed every 12 hrs
high-volume CVVH (100 mL/kg BW), filters changed every 12 hrs
CVVH ameliorated the initial serum tumor necrosis factor-alpha response and prevented sepsis-induced in vitro endotoxin hyporesponsiveness.
down-regulation of major histocompatibility complex II and CD14 expression on monocytes was significantly improved by CVVH.
improved oxidative burst and phagocytosis capacity in polymorphonuclear leukocytes suggested that leukocyte function was stabilized by CVVH.
CVVH significantly reduced bacterial translocation and endotoxemia.
Case Study 66 – year old man victim of
violent crime two gunshot sounds to abdomen unconscious & hypotensive on
arrival to ED 2 liters LR infusing 40% O2 via face mask
Case Study HR 130; RR 24; clear breath sounds
bilaterally; UO 300 mL; BP 110/76 emergency surgery to large bowel,
small bowel & vena cava colostomy performed EBL 2000; 10 units of pRBCs given surgery 6 hours; hypotensive during
surgery
paO2 / SaO2 85 / .95
pH 7.42
paCO2 / HCO3 38 /25
SIMV 14; TV 350; PEEP 10; FiO2 .40
Case Study hemodynamically stable day after
surgery extubated and placed on 40% venturi
mask 3 days later dyspneic & restless with
temperature of 103 F
DO2I = CI ( 1.38 x Hgb x SaO2) 10
4.5 X 1.38 X 8.8 X 0.88 x 10
481 mL/min/m481 mL/min/m22
(normal = 360 - 600 mL/min/m(normal = 360 - 600 mL/min/m22))
VO2I = CI X 1.38 X Hgb X (SaO2 - SvO2) X 10
4.5 x 1.38 x 8.8 x (.88 - .82) x 10
33 mL/min/m33 mL/min/m22
(Normal 108 - 165 mL/min/m(Normal 108 - 165 mL/min/m22))[email protected]
Case Study day 5 post op BP drops respirations shallow & labored; marked
accessory muscle use
Case Study day 10 post op condition deteriorates dopamine 22 mcg/kg/min responds only to pain PVCs & S3 gallop
Amylase 300 AST/ALT 80/100 BUN 40 Lipase 40 FSP 40 Platelets 80,000 PT/PTT 21/97.5
Pangault C, Le Tulzo Y, Tattevin P, Guilloux V, Bescher N, Drenou B. Down-modulation of granulocyte macrophage-colony stimulating factor receptor on monocytes during human septic shock. Crit Care Med. 2006 Apr;34(4):1193–1201.
Le Tulzo Y, Pangault C, Amiot L, et al. Monocyte human leukocyte antigen-DR transcriptional downregulation by cortisol during septic shock. Am J Respir Crit Care Med. 2004 May 15;169(10):1144–1151.
Volk T, Schmutzler M, Engelhardt L, et al. Influence of aminosteroid and glucocorticoid treatment on inflammation and immune function during cardiopulmonary bypass. Crit Care Med. 2001 Nov;29(11):2137–2142.
Perry SE, Mostafa SM, Wenstone R, Shenkin A, McLaughlin PJ. Is low monocyte HLA-DR expression helpful to predict outcome in severe sepsis? Intensive Care Med. 2003 Aug;29(8):1245–1252