Multiple Organ Dysfunction Syndrome

Revised and reviewed 15 November 2016

OVERVIEW

  • Multiple Organ Dysfunction Syndrome (MODS) [aka multiple organ failure (MOF)] is a hypometabolic, immunodepressed state with clinical and biochemical evidence of decreased functioning of the body’s organ systems that develops subsequent to an acute injury or illness.
    • ‘Dysfunction’ is preferred to ‘failure’, as the latter implies dichotomous “all-or-none” functioning rather than a spectrum, and implies irreversibility
    • Multiorgan failure refers to altered function in two or more organ systems during an acute illness such that homeostasis cannot be maintained without intervention
  • MODS contributes to about 50% of ICU deaths
  • Severity may be quantified using scoring systems such as the MODS score or the SOFA score
  • Organ recovery is frequently the rule in surviving patients without pre-existing organ disease
  • It remains unclear what triggers MODS or why it only seems to occur in certain patients

CAUSES

Almost any disease that results in tissue injury may result in MODS

  • Sepsis
  • Major trauma
  • Burns
  • Pancreatitis
  • Aspiration syndromes
  • Extracorporeal circulation (e.g. cardiac bypass)
  • Multiple blood transfusion
  • Ischaemia–reperfusion injury
  • Autoimmune disease
  • Heat-induced illness
  • Eclampsia
  • Poisoning/toxicity

MECHANISM

MODS occurs following an illness, injury or infection and involves a complex interplay of interdependent factors:

  • genetics
    • differences in gene expression and the proteome may account for individual differences in the likelihood and severity of MODS following a given stimulus
  • comorbidities
    • patients with premorbid organ dysfunction are more likely have further deterioration of organ function
  • medications, therapies and ICU supports
    • ventilator-induced lung injury contributing to pulmonary cytokine release and acute respiratory distress syndrome (ARDS)
    • also: fluid therapy, hypothermia, ECMO, immobility, inotropes, blood products, etc
  • macrocirculatory changes
    • systemic vasoplegia due to inflammation induced nitric oxide synthetase (iNOS)
    • reduced oxygen delivery (DO2) to tissues
  • microcirculatory changes
    • microvascular thrombi
    • reduced RBC deformability
    • increased blood viscosity
    • endothelial dysfunction
    • glycocalyx disruption
    • NO-mediated microvascular shunting
  • inflammation
    • dysregulation of proinflammatory factors leads to a systemic inflammatory response
      • mediated by multiple cytokines (e.g.  IL6, TNFaplha, INFgamma)
      • involves multiple intracellular signalling pathways (e.g. NFKB, Toll-like receptors, HMGB-1)
    • gut translocation of micro-organisms may play a role in precipitating and/or perpetuating this inflammatory response
    • compensatory anti-inflammatory response (CARS) results in immunosupression and anergy
      • mediated by anti-inflammatory factors (e.g. IL4, IL10)
      • involves TNFalpha suppression, HLA downregulation, and lymphocyte apoptosis
  • coagulation cascade
    • triggered by tissue factor, endotoxins, cytokines and bacterial antigens
  • neuro-endocrine factors
    • neurally mediated immune-suppression
    • stress responses involving adrenal hormones
    • hypothyroid state due to production of inert reverse T3
  • mitochondrial dysfunction
    • may be mediated by humoral factors
    • may contribute to cellular dysoxia and organ dysfunction

The relative of importance that these factors take may vary according to:

  • initiating insult
  • stage of illness
  • underlying organ reserve
  • nature and timing of therapies provided

All of these factors likely influence:

  • the number and type of organs affected
  • the severity of organ dysfunction

In particular, decreased mitochondrial activity appears to play a key role in the processes underlying MODS, both as a victim and a player:

  • Reduced ATP production will compromise normal metabolic functioning
  • To protect itself from dying, the cell may adapt by decreasing its metabolic rate, and this is clinically manifest as organ dysfunction
  • Mitochondrial modulation is potentially an important therapeutic target

Cell necrosis is an uncommon finding in MODS, though apoptosis plays a role (e.g. lymphocytic apoptosis)

  • MODS is primarily a functional disorder, rather than a structural disorder
  • MODS could be regarded as a transient state of metabolic shutdown analogous to hibernation
  • It may be that avoiding the detrimental effects of inappropriate and counter-adaptive iatrogenic interventions is  important

ASSESSMENT

Presence of a systemic inflammatory response (e.g. SIRS criteria) and dysfunction of at least 2 organs

  • may be mild, or fulminant resulting death

Organ dysfunction presents as:

  • Acute kidney injury (AKI) and uraemic acidosis
  • Acute Respiratory Distress Syndrome (ARDS)
  • Cardiomyopathy
  • Encephalopathy
  • Gastrointestinal dysfunction
    • increased intestinal permeability with bacterial and endotoxin translocation
    • decreased motility and ileus
    • pancreatitis
    • stress ulceration
    • acalculous cholecystitis
    • gut ischaemia
  • Hepatic dysfunction
  • Coagulopathy and bone marrow suppression

MANAGEMENT

Early recognition is important

Resuscitation

  • aggressive early therapy
  • manage in an ICU setting following initial resuscitation

Specific therapies

  • recognition and early control of inflammatory foci
  • clinical studies have not found benefit from targeting inflammatory mediators (e.g. antibodies against TNFalpha)
  • unclear role for glucocorticoids (no evidence of benefit)
  • unclear role for thyroxine supplementation

Supportive care and monitoring

  • multi-organ supports (e.g. RRT, mechanical ventilation, inopressors, extracorporeal supports and assist devices)
  • glucose control (e.g. BSL 6-10 mmol/L)
  • nutrition (preferably enteric; uncertain targets, composition of macronutrients or role for supplements)
  • avoid fluid overload

Seek and treat underlying cause, comorbidities, and complications (prevent secondary insults)

PROGNOSIS

  • Mortality 60-98% if 3 or more organ failures for >1 week (varies with age)
  • Circulatory failure is the most important predictor of poor outcome
  • SOFA score at day 6 is more predictive of Day 7 mortality than SOFA score on admission
  • About 50% of people with MODS will not return to work or normal function at 1 year follow-up

References and Links

LITFL

Journal articles

  • Boomer JS, To K, Chang KC, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306:(23)2594-605. [pubmed]
  • Cuesta JM, Singer M. The stress response and critical illness: a review. Critical care medicine. 40(12):3283-9. 2012. [pubmed]
  • De Backer D, Orbegozo Cortes D, Donadello K, Vincent JL. Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock. Virulence. 2014;5:(1)73-9. [pubmed]
  • Mongardon N, Dyson A, Singer M. Is MOF an outcome parameter or a transient, adaptive state in critical illness? Curr Opin Crit Care. 2009;15:(5)431-6. [pubmed]
  • Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med. 2004;32:(9)1825-31. [pubmed]
  • Seely AJ, Christou NV. Multiple organ dysfunction syndrome: exploring the paradigm of complex nonlinear systems. Crit Care Med. 2000;28:(7)2193-200. [pubmed]
  • Singer M. The role of mitochondrial dysfunction in sepsis-induced multi-organ failure. Virulence. 2014;5:(1)66-72. [pubmed]
  • Singer M, De Santis V, Vitale D, Jeffcoate W. Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet. 2004;364:(9433)545-8. [pubmed]

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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