Download Multiple Organ Dysfunction Syndrome

Systemic Inflammatory Response
Syndrome and Multiple Organ
Dysfunction Syndrome
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3 main types of shock
• A "shock combo shituation" is
far worse than shock of a
single type.
• Occurs when shock is severe.
• (For instance, a patient with
severe cardiogenic shock and
systemic ischemia can have
activation of the inflammatory
system (S.I.R.S.).
"cytokine storm"
• In severe shock the microcirculation changes dramatically.
• Those changes are mainly due to a induced by extremely severe
tissue ischemia or, directly, by a pathogen:
– (1) the endothelium is activated (vasodilates, becomes pro-coagulant,
expresses adhesion molecules),
– (2) monocytes are activated (and discharge numerous cytokines),
– (3) white blood cells obstruct some capillaries
– (4) disseminated intra-vascular coagulation and platelet aggregation plug
microcirculation as well.
When there is so much deterioration to the microcirculation, perfusion to
organs worsens rapidly....and, as a consequence, systemic shock also
worsens extremely rapidly...
vicious cycles fuel and exacerbate the
downhill course
• When tissue hypoxia starts to create multi organ
failure/dysfunction, each organ system suffers and often
influences negatively the state of shock .
• Many vicious cycles are at play in decompensated shock
stages.
• If treatment of the shock's cause is not successful or delayed,
"Cytokine storm" is in full bloom! ...and ... it is a catastrophic,
and often terminal
SIRS
• Simply….a severe systemic response to a critical
incident
• An abnormal host response to a variety of insults
• Characterized by generalized inflammation in organs
remote from the initial insult
• Normally, inflammatory process is contained within
confined environment
• If not, a wide spread systemic inflammatory response
occurs that is deleterious to organ function
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What is
S.I.R.S.
Systemic inflammatory
response syndrome
(SIRS)
is a general
inflammatory response
to various causes. It is
considered to be due to
cytokines ("cytokine
storm")
Clinical Manifestations of SIRS
• Temperature greater than 100.4° F (38°C) or less
than 97°F (36° C)
• Heart rate greater than 90 beats per minute
• Respiratory rate greater than 20 breaths per minute
or PaCO2 less than 32 mmHg
• White Blood Cell Count greater than 12,000 cells/ul
or less than 4,000 cell/ul or greater than 10%
immature (band) neutrophils
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Clinical Manifestations of SIRS
• May demonstrate
– Hypotension
– Confusion
– Hyperglycemia
– Thrombocytopenia
– Mild signs and symptoms to circulatory collapse
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Organ Manifestations
• Cardiovascular
– Skin warm and flushed
– Widened pulse pressure
– Cardiac output is increased but SVR is decreased
– Eventually C.O. declines exacerbating
hypoperfusion
Clinical Evidence of Organ Dysfunction
• Cardiovascular Failure
– HR<55beats/min
– MAP<50mmHg or systolic blood pressure <mmHg
– Ventricular tachycardia or fibrillation
– Cardiac Index<2.0L/min/m2
– Serum pH<7.25 with a PaCO2 <50mmHg
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Organ Manifestations
• Pulmonary
– Hypoxemia may be masked by hyperventilation
– Respiratory alkalosis
– Pulmonary edema
– Respiratory failure
– Bronchoconstriction
– ARDS
Clinical Evidence of Organ Dysfunction
• Respiratory Failure
– Severe dyspnea
– RR<6 or >50 breaths/min
– Chest X-ray with
decreased lung volumes
and bilateral diffuse
patchy infiltrates
– PaCO2 >50mmHg
– Crackles, wheezes
– PaO2/FIO2 <200
– Ventilatory
dependence>72hr
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Clinical Evidence of Organ Dysfunction
• Central Nervous
System Failure
– Glasgow Coma Scale<
(in absence of
sedation)
– Hypothermia or
hyperthermia
– Cardiovascular failure
– Respiratory depression
• CNS
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–
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Altered mental status
Confusion
Irritability
Agitation
Disorientation
Lethargy
Seizures
Coma
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Clinical Evidence of Organ Dysfunction
• Gastrointestinal
Failure
– Mucosal erosion on
endoscopy
– Perforation
– Upper or lower GI
bleeding
– Diarrhea
– Paralytic ileus
• GI
– Impaired motility
– Increased SGOT
– Increased SGPT
– Hyperbilirubinemia
– Hepatic necrosis
– Hypoglycemia
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Clinical Evidence of Organ Dysfunction
• Hepatic Failure
– Presence of both of the following:
• Serum bilirubin>6mg/dl (102.6 umol/L)
• Prothrombin time>4sec over control in the absence of
systemic anticoagulation
• Pancreatic Failure
– Elevated serum lipase and amylase
– Elevated serum glucose (often resistant to insulin
administration)
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Clinical Evidence of Organ Dysfunction
• Blood
– Hypoprothrombinemia
– Increased or decreased
WBCs
– Increased PT/PTT
– Increased or decreased
platelets
– Anemia
• Hematologic Failure
– White blood cell
count<1000/ul (1x103/L)
– Platelets< 20,000/ul
(20X109/L)
– Hematocrit <20% (.20)
– Bleeding studies
prolonged
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Treatment
•Supportive
•Medical
•Surgical
Nursing and Collaborative
Management
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•
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Prevention and treatment of infection
Maintenance of tissue oxygenation
Nutritional and metabolic needs
Support of failing organs
Research in SIRS and MODS
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Supportive Therapy
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Volume replacement
Positive inotropes
Vasopressors
Ventilation (PS or PEEP)
Nutritional Support
– Iso-osmotic feedings
– TPN
– PPN
– Immune Modulatory foods such Arginine, Glutamine
and fish oils
Clinical Manifestations of SIRS
•
•
•
•
•
Initially have mild restlessness or confusion
Hyperthermia
Tachycardia
Some increase in fluid requirements
Tachypnea with mild respiratory alkalosis
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Clinical Manifestations of SIRS
• Oliguria with reduced responsiveness to
diuretics
• Abdominal distention
• Hyperglycemia or increased glucose
requirements
• Patient appears acutely sick and unstable
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Clinical Manifestations of SIRS
• In advanced SIRS or MODS
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–
–
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Unstable and appears close to death
Unresponsive
Vasopressors and inotropic agents needed to maintain BP
Grossly edematous
Hypercapneic despite aggressive ventilation
Anuric
Liver and bili levels rise
Lactic acidosis worsens
Coagulopathy becomes impossible to correct
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Clinical Evidence of Organ Dysfunction
• Renal
– Oliguria <500 ml/day
– Urine Output<0.5 ml/kg/hr
– BUN>100mg/dl (35.7mmol/L)
– Serum creatinine>3.5mg/dl (309umol/L)
– Metabolic Acidosis
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Multiple Organ Dysfunction Syndrome
(MODS)
• End stage of a variety of injuries that terminate in
severe, generalized inflammation
• First recognized in the mid-1970s when advances in
in resuscitation and support technologies allowed
many individuals to survive life-threatening illness
or trauma only to die from complications of their
disease.
MODS
• The presence of altered organ function in an acutely ill
patient such that homeostasis cannot be maintained
without intervention.
• Primary MODS is the direct result of a well-defined insult
in which organ dysfunction occurs early and can be
directly attributable to the insult itself.
• Secondary MODS develops as a consequence of a host
response and is identified within the context of SIRS.
• The inflammatory response of the body to toxins and
other components of microorganisms causes the clinical
manifestations of sepsis.
MODS
• Results from an uncontrolled inflammatory
response to a severe illness or injury
• Initiated by severe injury or disease process that
activates a massive inflammatory response by the
host
• Sepsis and septic shock are most common cause
• Organ dysfunction can progress to organ failure and
death
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MODS
• Homeostasis cannot be maintained without
intervention
• Well-defined insult in which organ dysfunction
occurs early and can be directly attributable to
the insult itself
• Secondary MODS develops as a consequence
of a host response and is identified within the
context of SIRS
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MODS
• Triggers
– Severe trauma
– Major surgery
– Burns
– Circulatory shock
– Acute pancreatitis
– Acute renal failure
– ARDS
– Persistent inflammatory foci
– Necrotic tissue
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MODS
• People at greatest risk
– Age >65 years
– Baseline organ dysfunction (renal insufficiency)
– Bowel infarction
– Coma on admission
– Inadequate, delayed resuscitation
– Malnutrition
– Multiple blood transfusions (>6 units/12 hour)
– Persistent infectious focus
– Preexisting chronic disease (diabetes, cancer)
– Presence of hematoma
– Significant tissue injury
– Steroids
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Pathophysiology of MODS
• Progressive organ dysfunction
• excessive inflammatory reaction in organs distant
from site of original injury
• Host response is responsible
• Self-perpetuating inflammation
• Releases barrage of mediators, when stimulated by
the delayed postinjury insult
• These mediators damage the endothelium
throughout the body
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Pathophysiology of MODS
• Tachycardia, hypermetabolism, and increased
oxygen consumption, Cortisol, insulin, human
growth hormone, ADH, and endorphin levels
are increased
• Contributing to extreme catabolic state
• Endorphins vasodilate, decreasing SVR
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Pathophysiology of MODS
• SNS stimulated and amplified by factors including
pain, anxiety, psychosis, and hyperthermia
• Major plasma cascades are activated
• Stimulating release of histamine from mast cells
• They have strong chemotactic properties, C5a,
causes adhesion
• Activation and degranulation of neutrophils
• Because of endothelial cell damage and the release
of mediators starting at least 4 different cascade of
events involving mediator chains
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Pathophysiology of MODS
• Complement is exaggerated-inflammatory response
• Activation of kinin system activates bradykinin-vasodilator
• Coagulation mechanism activated-microvascular circulation
impaired-organ ischemia
• Fibrolytic mechanism activated
• Development of DIC
• Hyperinflammatory and hypercoagulant state contributes to
vasodilation, vasopermeability, cardiovascular instability,
endothelial damage, and clotting abnormalities
• Once cytokines and other mediators have been released and
the plasma enzyme cascades have been activated
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• A massive systemic inflammatory response develops
Pathophysiology of MODS
• TNF –potent metabolic effects
– Fever
– Anorexia
– Hyperglycemia
– Hypermetabolism
– Weight loss and muscle wasting
– Myocardial depression
– Activates neutrophils
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Pathophysiology of MODS
• Reperfusion injury
– Re-establishment of blood flow after a period of ischemia
– During ischemic episodes, energy stores and ATP are
depleted and the enzyme xanthine dehydrogenase is
converted to xanthine oxidase which attack the already
damaged tissues
– Although reperfusion is necessary to restore oxygen supply
to ischemic organs, it can increase the extent of injury
– Because of supply-dependent oxygen consumption and
reperfusion injury, tissues become increasingly hypoxic
– Result is cellular acidosis, impaired cellular function, and
ultimately multiple organ failure
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Clinical Manifestations of MODS
• Pulmonary
– Adult respiratory distress syndrome
– Pattern of respiratory failure
•
•
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•
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Dyspnea
Patchy infiltrates
Refractory hypoxemia
Respiratory acidosis
Abnormal O2 indices
– Pulmonary hypertension
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Clinical Manifestations of MODS
• Gastrointestinal
– Abnormal distention and ascites
– Intolerance to enteral feedings
– Paralytic ileus
– Upper and lower gastrointestinal bleeding
– Diarrhea
– Ischemic colitis
– Mucosal ulceration
– Decreased bowel sounds
– Bacterial overgrowth in stool
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Clinical Manifestations of MODS
• Liver
– Increased serum bilirubin
level
– Increased liver enzyme levels
• AST, ALT, LDH
– Increased serum ammonia level
– Decreased serum transferrin level
– Jaundice
– hepatomegaly
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Clinical Manifestations of MODS
• Gallbladder
– Right upper quadrant tenderness or pain
– Abdominal distention
– Unexplained fever
– Decreased bowel sounds
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Clinical Manifestations of MODS
• Hypermetabolism
– Decreased lean body mass
– Muscle wasting
– Severe weight loss
– Negative nitrogen balance
– Hyperglycemia
– Hypertriglyceridema
– Increased serum lactate levels
– Decreased serum albumin, serum transferrin, prealbumin, retinol-binding protein
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Clinical Manifestations of MODS
• Renal
– Increased serum creatinine level and Blood urea
nitrogen
– Oliguria, anuria, or polyuria consistent with
prerenal azotemia or acute tubular necrosis
– Urinary indices consistent with prerenal azotemia
or acute tubular necrosis
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Clinical Manifestations of MODS
• Cardiovascular
–Hyperdynamic
• Decreased PAOP
• Decreased SVR
• Decreased RAP
• Decreased LVSWI
• Increased oxygen consumption
• Increased C.O., CI, and HR
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Clinical Manifestations of MODS
• Cardiovascular
–Hypodynamic
• Increased SVR
• Increased RAP
• Increased LVSWI
• Decreased oxygen delivery and
consumption
• Decreased C.O. and CI
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Clinical Manifestations of MODS
• Central Nervous System
– Lethargy
– Altered LOC
– Fever
– Hepatic encephalopathy
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Clinical Manifestations of MODS
• Coagulation and Hematologic
– Thrombocytopenia
– Disseminated Intravascular Coagulation
• Immune
– Infection
– Decreased lymphocyte count
– energy
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MODS
Evaluation and Treatment
• No specific therapy
• Lots of experimentation
• Therapeutic management of MODS is
prevention and support
• Supportive measures initiated ASAP
– Identifies where the person is on the
continuum of illness
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MODS
Evaluation and Treatment
• Severity of illness scoring system
– Acute Physiology And Chronic Health Evaluation II
and III (APACHE II and III)
– Assesses prognosis in large group, not individually,
and therefore not well adapted for clinical
decision making
– More useful in the research studies
– Individual variables to describe relative risks of
individuals
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MODS
Evaluation and Treatment
• Initial source of inflammation must be eliminated or
controlled
• Second insult must be eliminated
• Remove any potential site of infection by debriding
necrotic tissue, draining abscesses, reducing number
of invasive procedures performed, removing
hematomas
• Nosocomial infection rates of 15% to 25% have been
reported in critically ill individuals
• Early reduction of long-bone fractures and surgical
repair of injured tissues
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MODS
Evaluation and Treatment
• Goals of therapy
– Control infection and inflammation
• Monoclonal antibiotics-modulate or inhibit
the immune and inflammatory responses
• Anti-inflammatories
• Antioxidants and free radials scavengers
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MODS
Evaluation and Treatment
• Goals of therapy
– Provide adequate tissue oxygenation
• Oxygen saturation must be above 90% at all times
• Hemoglobin levels should be kept above 10 to
12g/dl
• Mechanical ventilation with high oxygen
concentrations and PEEP
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MODS
Evaluation and Treatment
• Goals of therapy
– Restore intravascular volume
• Aggressive fluid resuscitation
– Support the function of individual organs
• “Need to feed” (keeps gut alive, hypermetabolism,
catabolism)
• Dialysis
• Inotropic drugs
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