Download Critical care Immunology

Leanna R. Miller, RN, MN, CCRN-CMC, PCCN-CSC, CEN, CNRN, NP
Education Specialist
LRM Consulting
Nashville, TN
lrmmiller@msn.com
 Learning Outcomes
 Analyze
the mediators (cytokines)
responsible for cellular and clinical
changes during the inflammatory response.
 Correlate the clinical significance of
immunoparalysis to trauma, sepsis and
open heart surgery.
 Evaluate strategies used to manage
patients with immunoparalysis.
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recovery from critical illness requires proper
immunologic balance between pro- and antiinflammatory forces
persistence of a marked compensatory antiinflammatory innate immune response
following an insult such as sepsis, surgery, or
trauma is termed immunoparalysis
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an acquired immunodeficiency can be
quantified through the measurement of:
 monocyte cell-surface HLA-DR
expression
 analysis of the capacity of whole blood
to produce TNFα upon ex vivo
stimulation with endotoxin
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during critical illness, there is a
systemic anti-inflammatory state
intended to avoid the spread of
the local proinflammatory
response
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resulting immunosuppression
increases the risk of nosocomial
infections
 related to an increase in morbidity
and mortality in critically ill patients
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 Host Defenses
 exposed
to injury &
infection
 defense mechanisms
inflammation
thrombosis
healing
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 Stages of Inflammation
 destruction
& removal
 containment
 stimulation & amplification
of the immune response
 promotion of healing
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Innate - Cellular
Adaptive - Cellular
Phagocytosis
Monocytes
Neutrophils
Dendritic Cells
Antibody Production
B cells / Plasma cells
Antigen Presentation
Monocytes
Dendritic Cells
Cytotoxic Killing
CD8 T cells
Cytotoxic Killing
Natural Killer Cells
Neutrophils
Cytokine & Chemokine Production
CD4 T cells
Cytokine & Chemokine Production
All of the above
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Innate - Noncellular Elements
Cytokines
Chemokines
Complement
Adaptive – Noncellular Elements
Immunoglobulins
Cytokines
Chemokines
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 Nonspecific Immunity
 natural
killer cells (NK)
kill viruses, bacteria,
neoplastic cells
regulate production of
erythrocytes &
granulocytes
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 Complement
 activated
by:
 antigen/antibody
complex
 tissue
injury
 tissue ischemia
 coagulation
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 Complement
 activated
by:
 cell
debris
 kinins
 endotoxin
 bacterial cell debris
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 Complement
opsonization
mediator
release
histamine
leukotrienes
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 Coagulation
activated
by:
Intrinsic
pathway
Extrinsic pathway
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 Coagulation
excessive
intravascular
coagulation leads to:
vascular damage
tissue ischemia
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 Fibrinolysis
 Hemorrhage leads
to:
decreased O2 delivery
tissue ischemia
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 Tumor Necrosis Factor
 fever
 endothelial damage
 anorexia
 procoagulant activity

responsiveness to
catecholamine
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 Triggers to IIR
 infection
 hypoperfusion
 hypoxemia
 injury
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 Etiology
 ARDS
 Sepsis
 DIC
 ATN
 Shock
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Activation of the Immune Response
COAGULATION CASCADE
Endothelium
Tissue Factor
Factor VIIIa
PAI-1
IL-6
IL-1
TNF-
Monocyte
Factor Va
Suppressed
fibrinolysis
THROMBIN
Neutrophil
Fibrin
IL-6
Fibrin clot
Tissue Factor
Inflammatory Response
to Infection
TAFI
Thrombotic Response
to Infection
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Fibrinolytic Response
to Infection
 Pathophysiology
 role
of initial insult in
promoting INFECTION
Immunosuppression
 downregulation
 blood
stress
products
response
 hypercatabolism
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 Pathophysiology
 Transluminal
migration
SIRS
nosocomial
pneumonia
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 Pathophysiology
Flow
dependent
O2 consumption
DO2 > 600
VO2 > 150
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 Pathophysiology
 tissue
ischemia and
reperfusion
xanthine oxidase 
O2 free radicals
(ROS)  tissue
injury
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 Mortality rates
 One
organ
= 1%
 Two organs
= 11%
 Three organs = 50%
 Four organs = 75%
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 Nurse’s Role in Treatment
 assessing
system failure
 early identification
 minimizing complications
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 SIRS Criteria
(2 or more)
 Temperature
> 38 °C or
SIRS???
< 36 °C
 Heart rate > 90 beats
 RR > 20 or paCO2 < 32
 WBC > 12,000 or < 4,000
or > 10% bands
Levy et al. 2001 International Sepsis Definitions Conference
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 Definitions
 SIRS
 SIRS
+ Infection = Sepsis
 Sepsis + Acute Organ
Dysfunction or hypoperfusion
= Severe Sepsis
 Severe Sepsis + CV failure =
Septic Shock
 Most common sites
of origin
 Urinary
tract
 GI system
 Respiratory tract
 Skin & wounds
 Predisposing Factors
 extremes
in age
 granulocytopenia
 prior antibiotic use
 severe burn, trauma, surgery
 functional asplenia
 Predisposing Factors
 immunosuppression
 malnutrition
& TPN
 alcohol & drug abuse
 prolonged ICU stay
 Assessing Acute Immune
Inflammatory Response
 Procalcitonin (PCT) 0.12 – 0.26
ng/mL
C
– reactive protein (CRP) 0 – 5
mg/L
 IL
–6
0 – 28 pg/mL
Hermann et al;(2000) Procalcitonin in septic shock. Clin
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Chem Lab Med 38(1):41 - 46
1st Six Hours
Resuscitation =
Cultures + Antibiotics + Early Goal – Directed Therapy
1st Six Hours
 Delays in management of the
SIR result in higher mortality
rates and increased utilization
of hospital resources
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Transition from Sepsis to
Severe Sepsis
 occurs most often during the
1st 24 hours of hospitalization
 increase in mortality of 20 –
46%
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Transition
  tissue O2 delivery & CV
insufficiency accompanies
transition
 usually not detected by VS
nor SIRS criteria
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O2 Transport & Utilization
 O2 delivery is insufficient to
meet O2 demands @ cell level
 results in increased lactate
levels
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O2 Transport & Utilization
 SvO2 < 65% or ScvO2 < 70%
result in increased lactate and
suggest the presence of
global tissue hypoxia –
greater extraction by tissues
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O2 Transport & Utilization
 high SvO2, ScvO2 & lactate
indicates that despite
adequate global systemic O2
delivery, the tissues are
unable to extract the O2
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Sepsis Pathophysiology
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Identification of High Risk Patient
 single lactate > 4.0 or more at initial
presentation
 failure to clear lactate levels during
the 1st 6 hours is associated with
increased morbidity and mortality
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 Management of IIR
 Initial

Resuscitation
Endpoints
CVP 8 to 12 mm Hg
 MAP > 65 mm Hg
 UO > 0.5 mL/kg/hr
 SvO2 > 70%

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 Management of IIR
 Early
antimicrobial therapy
empiric
antibiotics within
4 to 8 hours of hospital
presentation

Surviving Sepsis
Campaign recommends
antibiotics within 1 hour
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 Management of IIR
 source
of infection & local
hospital sensitivity &
resistance patterns
 surgical consultation
 resistant organisms when
patients live in nursing homes
or are IV drug users
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Volume Therapy
 repletion of intravascular volume
 rapid, 20 mL/kg boluses of either
crystalloid or colloid
 CVP 8 – 12 mm Hg
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Volume Therapy
 4% albumin or NS
 found no significant difference in
mortality between the group
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Vasoactive Agents
 Norepinephrine 2 – 20 g/min
 Vasopressin 0.01 – 0.04 units/min –
(VASST study)
 Phenylephrine 40 – 300 g/min
 Dopamine 5 – 20 g/kg/min
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Vasoactive Agents
 Adverse consequences
 splanchnic hypoperfusion
 excess tachycardia
 coronary ischemia
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RBC Replacement
 If ScvO2 remains < 70% after
optimization of preload, afterload
and arterial O2 saturation
 increase Hct to 30%
 optimal erythrocyte transfusion
 fresh vs. stored blood
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Inotropic Therapy
 Sepsis may be accompanied by myocardial
suppression in 10 – 15% of patients
 dobutamine titrated at 2.5 g/kg/min
every 20 – 30 minutes to ScvO2 of 70%
 milrinone (long half – life and accumulates
in renal failure)
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Decreasing O2 consumption
 intubation, sedation, analgesia
 control fever
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Administration of steroids, has
theoretical benefits in the setting
of severe sepsis by inhibiting
the massive inflammatory
cascade
Steroid Therapy
 Inflammatory cascade leads to (RAI):
 inadequate release or response to
ACTH
 peripheral steroid resistance @
receptor level
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Steroid Therapy
 If on vasopressors, draw random cortisol
level; if < 25 mcg/mL give corticosteroids
 If not on vasopressor, draw baseline
random cortisol level, do cort stim test;
get levels @ 30 & 60 min – if difference is
< 9  give steroids
Steroid Therapy
 low doses of hydrocortisone decreased
requirement for vasopressors and lowered
mortality
Hydrocortisone 50 mg IV every 6 hours
 Dexamethasone 4 mg IV every 8 hours
 Fludrocortisone 100 g PFT every day

Protective Lung Strategies
 6 mL/kg vs. 12 mL/kg
 9.9% absolute 28 – day mortality
in low TV group
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Tight Glycemic Control
 100 – 150 mg/dL
 8.0% reduction in mortality
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High – volume Hemofiltration
 removal of inflammatory cytokines
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CVVH for Treatment
low-volume CVVH (20 mL/kg BW),
filters changed every 12 hrs
high-volume CVVH (100 mL/kg
BW), filters changed every 12 hrs
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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.
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improved oxidative burst and
phagocytosis capacity in
polymorphonuclear leukocytes
suggested that leukocyte function was
stabilized by CVVH.
CVVH significantly reduced bacterial
translocation and endotoxemia.
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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
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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
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BP
RAP / PAOP
SVR
CI
SvO2
120/64/76
6/8
1027
3.5
.74
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paO2 / SaO2
pH
paCO2 / HCO3
85 / .95
7.42
38 /25
SIMV 14; TV 350; PEEP 10; FiO2 .40
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Na
K
Cl
Glucose
Hgb/PCV
WBC
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132
4.8
98
230
12.1 / 35
12,000
Case Study
 hemodynamically stable day after
surgery
 extubated and placed on 40% venturi
mask
 3 days later dyspneic & restless with
temperature of 103 F
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BP
RAP / PAOP
SVR
CI
SvO2
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128/68/80
2/7
983
4.1
.72
paO2 / SaO2
pH
80 / .95
7.47
paCO2 / HCO3
32 /24
FiO2 .40 mask
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Hgb/PCV
10.2 / 30
WBC
20,000
Platelets
150,000
CT scan of abdomen
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DO2I = CI ( 1.38 x Hgb x SaO2) 10
4.5 X 1.38 X 8.8 X 0.88 x 10
481
2
mL/min/m
(normal = 360 - 600 mL/min/m2)
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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/m2
(Normal 108 - 165 mL/min/m2)
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Case Study
 day 5 post op
 BP drops
 respirations shallow & labored; marked
accessory muscle use
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BP
HR
RAP / PAOP
SVR
CI
SvO2
82/58/70
122
2/5
569
5.3
.88
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paO2 / SaO2
pH
55 / .88
7.26
paCO2 / HCO3
35 /12
FiO2 .40 mask
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Case Study
day 10 post op
condition deteriorates
dopamine 22 mcg/kg/min
responds only to pain
PVCs & S3 gallop
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BP
HR
RAP / PAOP
SVR
CI
SvO2
74/58/70
156
7/22
1600
2.8
.50
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paO2 / SaO2
pH
45 / .87
7.10
paCO2 / HCO3
50 /10
FiO2 .50 SIMV
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Na
K
Cl
Glucose
Creatinine
Hgb/PCV
WBC
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150
6.1
98
230
3.5
12.1 / 35
12,000
Amylase
AST/ALT
BUN
Lipase
FSP
Platelets
PT/PTT
300
80/100
40
40
40
80,000
21/97.5
lrmmiller@msn.com
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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
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