Multiple Organ Dysfunction Syndrome (MODS)

History & Epidemiology

Tilney et al. 1973: First description Fry et al. 1980: role of infection and temporal

sequence of organ failure LungLiverGastric Mucosakidney (Variations of this sequence can occur !)

History & Epidemiology

American College of Chest physicians/Society of

Critical Care Medicine: Progressive physiologic failure of several organs in acutely ill patients, such that homeostasis could not be maintained without intervention
Primary MODS: direct organ-system injury or

accompanying hemodynamic alterations Secondary: Exaggerated host response to the inciting insult, usually manifesting after a latent period

History & Epidemiology

A leading cause of morbidity and mortality for ICU

patients Present in 47% of adult ICU patients (variable)

Discrete syndrome with a common and measurable

pathologic basis ? Not at all clear whether MODS is a single pathologic process with highly variable clinical expression or simply the limited phenotypic expression of a large number of pathologically divergent processes.

History & Epidemiology

Who is at risk ? Not

limited to patients with sepsis

History & Epidemiology

One of the most common causes of death in non-

coronary intensive care units Prognosis related to severity of MODS and number of involved organs

History & Epidemiology

Angus et al. 2001:
Number of organs involved in MODS
1 2 3 4+

Incidence

Mortality

73.6% 20.7% 4.7% 1%

21.2% 44.3% 64.5% 76.2%

Scoring systems
Multiple Organ Dysfunction Score Sequential Organ Failure Assessment Score Logistic Organ Dysfunction System

Scoring systems

Mediators and methods of organ dysfunction

Key concepts: 1. 2.

3.
4.

5.

Dysregulated immune response The role of the gut Nosocomial or iatrogenic insults Complete recovery is possible therefore etiology more likely to be functional (vs. structural) Non uniform mechanisms

1. Dysregulated immune response

Loss of homeostasis

between systemic inflammation and a counter balancing antiinflammatory response

Loss of immune

compartmentalization

1. Dysregulated immune response

Role of uncontrolled infection ?

Triggers MODS POSSIBLY not as important in the evolution of the syndromewhy?

Vascular endothelial injury

Mediated by leukocyte derived mediators, plateletleukocyte-fibrin thrombi and TNF-alpha.

2. The role of the gut

Potentially the

motor of MODS.

Clark and

Coopersmith: 3 components

2. The role of the gut

1) Intestinal epithelial hyper permeability: Common in critical illness Detectable before the onset of the syndrome 2) Gut associated lymphoid tissue (GALT) Inadequate function reduced mucosal IgA levels Pneumonia

2. The role of the gut

3) Enteric commensal bacteria Gut derived sepsis (Alverdy et al.):
Disruption in microenvironmentactivation of virulence genes

1+2+3=loss of immune compartmentalization

Nosocomial and iatrogenic promoters of MODS

two hit hypothesis:
1. Severe trauma + associated tissue hypoperfusion primes

leukocytes
2. Ventilator-associated pneumonia

blood transfusion abdominal compartment syndrome

A few more potential mechanisms

Respiratory system
Typically the first organ to be involved Failure of normal gas exchange
1. 2.

atelactasis, intravascular thrombosis or altered regional flow ventilation/perfusion mismatch. Increased capillary permeability alveolar flooding ARDS (type I & III)

Type IV respiratory failure: hypoperfusion of respiratory muscles in patients in shock

Respiratory system

Respiratory system
Complications ?

Ventilator induced lung injury

Solution ?

Low tidal volume (6ml/Kg) ventilation

Renal
Acute kidney injury (AKI)

Renal

Renal
USA: 700,000 cases of sepsis each year, AKI

complicates more than 50% of these.

Cardiovascular
Acute cardiovascular derangements of MODS: 1. Generalized reduction in peripheral vascular tone 2. Generalized increase in capillary permeability

3. Alterations in regional blood flow to specific organs

4. Microvascular plugging and stasis 5. Myocardial depression septic cardiomyopathy

Cardiovascular

Reduce afterload Increase preload Improve myocardial contractility Control heart rate and rhythm

Gastrointestinal & Hepatic

G.I. Signs: nausea, vomiting, nasogastric aspirates can be

early signs of regional circulatory failure Splanchnic vasoconstriction gut mucosal ischaemia MODS G.I. manifestations:
1. 2. 3. 4.

5.

Loss of gastric acid production Stress ulceration Bleeding Ischaemia Pancreatitis

Early enteral nutrition most effective strategy for gut

mucosal protection

Gastrointestinal & Hepatic

Hepatic circulation compromised by the same factors

which lead to splanchnic vasoconstriction Release of inflammatory mediators from activated Kupffer cells Typically manifests as ICU jaundice and cholestasis. Shock liver centrilobular hepatocellular necrosis Treatment is non-specific: enteral feeding, improve splanchnic blood flow

Hemostatic abnormalities
Cytokine prothrombotic abnormalities within

microcirculation Inappropriate intravascular coagulation could be the final pathway to organ dysfunctuion Disseminated intravascular coagulation: Powerful predictor of subsequent organ dysfunction (Longitudinal study of 136 patients with multiple trauma, Gando et al.)

Neurological
Continuum of states of

reduced alertness Coma Stupor Somnolence (drowsiness)

Neurological
A reduced Glasgow Coma Score is the most readily recognizable manifestation of the neurological dysfunction of MODS.

Neurological
Delerium:

Acute onset of changes or fluctuations in the course of mental status 2. Inattention 3. Disorganized thinking 4. Altered level of consciousness
1. 80% of mechanically ventilated ICU patients

Neurological
Hypoxic ischemic encephalopathy Metabolic encephalopathies Septic encephalopathy

Acute alteration in the level of consciousness accompanying severe sepsis Most common in ICU

Management
Recognize patients at greatest risk ! Individualized therapy Minimize risk of progression to MODS 1. Optimization of supportive management of circulatory

and respiratory dysfunction 2. Reducing the rate of protein catabolism 3. Early nutrition support by the enteral route 4. Selective, targeted use of antibiotics 5. Minimizing blood transfusions

Read Surviving sepsis campaign guidelines (2008)

Case studies
Frank Cerra: typical clinical course of MODS in the

surgical patients Stage 1: Acute event associated with hypotension Stage 2: Active resuscitation (24hrs) Stage 3: Stable hypermetabolism (7-10 days) Clinical onset of MODS: low grade fever, tachycardia and dyspnea. Mental confusion. Patchy infiltrates on chest X-ray. DIC and thrombocytopenia. What next?

Case studies
Pulmonary status worsens intubation and mechanical

ventilation Hyperdynamic circulation Urine urea nitrogen output is substantial Glucose intolerance and hyperlactatemia 7-10 days later Hyperbilirubinemia and increased serum creatinine Bacteremia Requires more inotropic support Deterioration of renal function, worsening encephalopathy and G.I. Bleeding Stage 4: (14-21 days later) Renal failure requiring dialysis Death: 21-28 days after the initial event