[N109] Multi-Organ Dysfunction Syndrome (MODS)

SIRS, sepsis, septic shock

What 3 clinical syndromes threaten survival & quality of life, often leading to MODS?

A systemic response to infection with clinical features such as:

• SBP < 90 mmHg

• Acute mental status change

• PaO2 < 60 mmHg (PaO2/FiO2 < 250)

• Lactic acidosis

• Oliguria

• DIC / platelets < 80,000

• Liver enzymes > 2x normal

Define Sepsis.

Systemic Inflammatory Response Syndrome (SIRS)

A systemic inflammatory response to infection, ischemia, infarction, or injury → disrupts microcirculation, organ perfusion, leading to secondary organ dysfunction

Septic Shock

Sepsis with blood pressure problems (persistent hypotension despite fluids, requiring vasopressors)

MODS

Altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention

Severe sepsis with associated MODS

What is the leading cause of death in adult ICUs?

MODS (90% of deaths in PICU).

What is the major cause of death in pediatric ICUs?

• Advancing age/prematurity

• Number of dysfunctional organs

• Prolonged organ failure

• Delayed diagnosis

• Inadequate resuscitation/source control

MODS mortality increases with what factors? (Name 3).

• 1 → 40%

• 2 → 60%

• 3 → 95%

• 5 → 100%

Mortality rate in adults with MODS:

• 1 organ affected = ?

• 2 organs = ?

• 3 organs = ?

• 5 organs = ?

26–50% (lower than adults but accounts for 90% of PICU deaths)

Mortality of pediatric MODS?

Shock

A state of inadequate tissue perfusion → cellular dysfunction & death

• Low blood flow (cardiogenic, hypovolemic)

• Maldistribution of flow (neurogenic, anaphylactic, septic)

Main mechanisms of shock?

MI, dysrhythmias, cardiomyopathy, structural heart issues

Causes of cardiogenic shock?

Trauma, hemorrhage

Causes of hypovolemic shock?

Spinal cord injury, opioid overdose (loss of sympathetic tone)

Causes of neurogenic shock?

Severe allergic reaction, multiple transfusions

Causes of anaphylactic shock?

Infection or pancreatitis leading to uncontrolled inflammatory response

Causes of septic shock?

• Mediator excess (TNF, ILs, free radicals)

• Endothelial injury

• Vasodilation + ↑ permeability (leaky capillaries, hypotension)

• Tissue edema

• Neutrophil entrapment → hypoxia

Key processes in SIRS (name 4)

• SIRS = body’s fire alarm (response to infection/injury)

• Sepsis = SIRS caused by infection

• All sepsis has SIRS, but not all SIRS is sepsis

What is the relationship between SIRS and Sepsis?

Progressive dysfunction of ≥2 organ systems due to hypoperfusion & inflammation

What defines MODS?

Cardiovascular, lungs, GI, liver, CNS, kidneys, skin

Target organs most affected in MODS?

• Immunosuppressive therapy (transplants, corticosteroids)

• Elderly, diabetics, cancer, organ failure

• Invasive devices (catheters, intubation)

• Indiscriminate antibiotic use

• Chronic diseases (neutropenia, cirrhosis, DM, AIDS)

• Surgery/instrumentation

• Prior drug therapy (immunosuppressants)

• Trauma, burns, childbirth, septic abortion

Major risk factors for sepsis (name 5)

Males >40, females 20–45

Which age/sex groups are more at risk?

Temp, HR, RR, WBC (1–4) + PaCO₂ (low)

What are the basic SIRS parameters?

True

(T/F): All sepsis cases involve SIRS, but not all SIRS cases are sepsis

Dysfunction of ≥2 organ systems due to dysregulated inflammatory & hormonal responses

What is MODS in simple terms?

Hormonal, cytokine, and immune changes → systemic inflammation, procoagulant state, organ dysfunction

What systemic effects drive MODS?

Catecholamines, cortisol, growth hormone, glucagon, insulin (with resistance)

Which stress hormones rise in MODS?

Hyperglycemia, proteolysis, lipolysis, ↑ lactate

What are the catabolic effects of stress hormones in MODS?

↑ cytokines, oxidative stress, leukocyte adhesion/migration

What are the inflammatory effects of stress hormones?

Immunosuppression, ↑ infections, multi-organ failure, ↑ mortality

What are the systemic consequences of MODS hormonal dysregulation?

Complement proteins, neutrophil/macrophage activation, free radical release

What immune system processes are activated in MODS?

TNF-α, IL-1β, IL-6, IL-8, IL-4, IL-10, interferons

Major cytokines in MODS?

Depleted → loss of anticoagulant effect → ↑ thrombin → ↑ clotting → DIC & ischemia

What happens to Protein C in MODS?

False — fibrinolysis is inhibited

(T/F): MODS is associated with increased fibrinolysis

↑ O₂ consumption, gluconeogenesis, protein catabolism, hyperglycemia

What are the metabolic changes in MODS?

Inflammation & metabolism persist → organs overcompensate → more damage → worsening dysfunction

Explain the “feed-forward cycle” of MODS

• Primary: Direct organ injury (trauma, ischemia).

• Secondary: Consequence of infection, poor perfusion

Differentiate Primary vs Secondary MODS

Complement, TNF, interleukins, platelet activating factor, toxic oxygen radicals

Name at least 3 humoral mediators in MODS

Neutrophils, monocytes/macrophages, platelets, endothelial cells

Name at least 3 cellular inflammatory mediators in MODS

Circulatory → CNS → Respiratory → Renal → Hematologic → GI/Liver → Endocrine → Immune

Typical sequence of organ dysfunction in MODS?

Tachycardia, hypotension, myocardial depression, arrhythmia, CHF

What happens in MODS-related circulatory failure?

Agitation, lethargy, coma

What CNS signs are seen in MODS?

Dyspnea, tachypnea, alveolar edema, V/Q mismatch, hypoxemia, ARDS

Respiratory system involvement?

Oliguria, fluid overload, electrolyte imbalance, uremia

Renal involvement?

Anemia, thrombocytopenia, coagulopathy, DIC

Hematologic involvement?

Ileus, bacterial translocation, malnutrition, poor protein synthesis, cholestasis

GI/Liver involvement?

Insulin resistance, hyperglycemia, adrenal insufficiency

Endocrine involvement?

Suppression of cellular & humoral immunity

Immune system involvement?

Fever, chills, fatigue/malaise, anxiety, confusion

Name 3 general nonspecific signs of sepsis/MODS

Lactulose

What drug is given to help excrete ammonia in hepatic encephalopathy?

ARDS, DIC, acute renal failure, GI bleeding, liver failure, CNS dysfunction, heart failure, death

List 2 complications of MODS

↑ volume requirements

What happens in Stage 1 MODS?

Occult organ dysfunction

What happens in Stage 2 MODS?

Overt dysfunction in multiple organs requiring support

What happens in Stage 3 MODS?

Sequential organ failure → death

What happens in Stage 4 MODS?

Procalcitonin (PCT)

What lab marker is most strongly linked with sepsis?

Measures 6 organ systems, predicts mortality in MODS

What is the significance of SOFA score?

0–24

(≥2 = sepsis-related dysfunction; ≥4 = severe derangement)

SOFA score ranges from?

CBC, metabolic profile, PCT, CRP, IL-6, blood cultures, urinalysis, cardiac enzymes, liver profile, lactate

Important labs in MODS workup?

Prevent/treat infection, maintain O₂, support nutrition/metabolism, support failing organs

Main management goals for MODS?

• ScvO₂ ≥ 70%

• MAP ≥ 65 mmHg

• Urine output ≥ 0.5 mL/kg/h

• Lactate clearance ≥ 10%/h

• Hb ≥ 7 g/dL

• Platelets ≥ 20,000/μL

First 6-hour resuscitation goals in MODS?

Norepinephrine

First-line vasopressor for septic MODS?

Early enteral nutrition

What type of nutrition is preferred in MODS?

False – There is no specific effective therapy. Management is mostly supportive and organ-specific

True or False: There is a specific drug therapy that can cure MODS

• Preventive strategies (avoid 1st and 2nd hits)

• Supportive care for organ failure

• Treat underlying cause (infection, trauma, etc.)

• Molecular therapy (experimental/adjunctive)

What are the 4 pillars of general MODS management?

• Primary MODS: Avoid initial multi-system injury/trauma.

• Secondary MODS: Avoid additional “second hits” in already primed/vulnerable patients.

What is the difference between Primary MODS prevention and Secondary MODS prevention?

Identify and eliminate the initial stimulus (e.g., infection, trauma, ischemia)

What is the first principle of MODS prevention and management?

The one with the lowest MIC (Minimum Inhibitory Concentration) effective against the pathogen

Which antibiotic is chosen in MODS treatment?

• Normal BP with IV fluids

• ScvO₂ ≥ 70%

• PRBC transfusion + inotropes if needed

What are the hemodynamic & O₂ delivery therapy targets in MODS?

Crystalloids (NS, LR, Plasmalyte).

Which fluids are usually first-line in MODS?

High bleeding risk and no proven survival benefit

Why is Activated Protein C (APC) no longer used in MODS management?

• (a) Stimulates neutrophil production (e.g., neutropenia)

• (b) Stimulates neutrophils + macrophages (immunoparalysis)

• (c) Reduces inflammation, stabilizes BP (shock refractory to fluids/pressors)

• (d) Provides antibodies (toxic shock, neonatal sepsis, hypogammaglobulinemia)

• (e) Improves microcirculation, reduces blood viscosity, ↓ inflammation (esp. in premature infants)

Match the immune therapies with their role:
a) G-CSF
b) GM-CSF
c) Steroids
d) IVIG
e) Pentoxifylline

Hydrocortisone + Fludrocortisone

Which combination of drugs is used in refractory septic shock with low cortisol response?

Neonates > children > adults

Which patients benefit the most from ECMO in MODS?

• VA-ECMO supports both heart and lungs.

• VV-ECMO supports lungs only.

What is the difference between VA-ECMO and VV-ECMO?

• Tidal volume ~6 mL/kg predicted body weight

• Plateau pressure <30 cm H₂O

• PEEP to prevent alveolar collapse

• Permissive hypercapnia allowed

What are the lung-protective ventilation parameters for ARDS in MODS?

In unresolving ARDS (>1 week, culture-negative, proliferative phase)

When are steroids considered in ARDS management?

CVVHD (continuous venovenous hemodialysis)

Which renal replacement therapy is preferred in unstable MODS patients?

Peritoneal dialysis catheter for decompression

How is abdominal compartment syndrome managed in MODS?

False – It must be controlled with insulin (NAIL protocol)

True or False: Hyperglycemia in MODS should be tolerated because it supports immune function

Anticoagulants in select cases + blood product replacement

What is the management approach to DIC in MODS?

Antioxidants like N-acetylcysteine, vitamins C & E, beta carotene

Which substances may help neutralize free radicals in MODS?

c) Give ≥60 mL/kg fluids, use norepinephrine/epinephrine

Multiple Choice — Which of the following reflects the current (NOW) approach to MODS?
a) Avoid fluid boluses >20 mL/kg
b) Avoid vasopressors in pediatric septic shock
c) Give ≥60 mL/kg fluids, use norepinephrine/epinephrine
d) ECMO does not work in MODS

True

True or False: Steroids are now considered in adrenal insufficiency or refractory septic shock, unlike before when they were avoided

Recognition that children die not just from “too much inflammation” but also from immunoparalysis and infection control failure → leading to therapies like GM-CSF, IVIG

What key shift in understanding caused sepsis/MODS management to change?

Dysfunctional ventilatory weaning response

Which nursing diagnosis is unique to MODS patients who struggle with ventilator weaning?

• Prevention & treatment of infection

• Maintenance of tissue oxygenation

• Nutritional & metabolic support

What are the 3 main goals of nursing interventions in MODS?

True

True or False: In MODS, both enteral and parenteral nutrition may be used, depending on GI function

• Normal: > 0.9 mg/dL

• 1-20 mg/dL: rheumatoid arthritis (inflammation)

• > 50 mg/dL: bacterial

Normal and Abnormal levels of C-reative protein

Tests the specific protein in the blood that is released by the liver in response to the inflammation

what does C-reative protein tell us?

• Normal: 0.5 to 2.2 mmol/L

• >2 = hyperlactatemia

• More than 4 = lactic acidosis

Normal and Abnormal levels of blood lactate

• 0 = no MODS (normal)

  • Mortality rate = 5% (medyo mababa)

• 4 or more = severe physiologic derangement

  • Mortality rate = >50%

System related Organ Failure Assessment (SOFA) interpretation

• Respiratory = PaO2/FiO2 ratio

• Coagulation = platelet count

• Liver = serum bilirubin

• Cardiovascular = Mean Arterial Pressure or vasopressor use

• CNS = GCS

• Renal = creatinine level or urine output

What are the organ system and the corresponding SOFA parameters?

• Central Venous Oxygen Saturation (ScvO2) ≥ 70%

• Mean Arterial Pressure (MAP) ≥ 65 mmHg

• Urine output ≥ 0.5 mL/kg/h

• Lactate clearance ≥ 10%/h

• Hemoglobin ≥ 7 g/dL

• Platelet count ≥ 20,000/μL

What are the goals for MODS for the first 6 hours?

• Fluid resuscitation:

  • Crystalloids (e.g., saline)

  • Colloids (e.g., albumin)

• Vasopressors:

  • Norepinephrine (first-line)

  • Epinephrine

• Inotropes:

  • Dobutamine

• Blood transfusions:

  • Red blood cells

  • Platelets

• Oxygen therapy:

  • Mechanical ventilation

  • Supplemental oxygen

• Nutritional support:

  • Early enteral nutrition

Therapeutic Interventions in MODS?

• Normal BP with IVF and SVC O2 sat > 70%

parameters for hemodynamic & O2 delivery therapy in MODS

crystalloids

common IV fluid of choice in MODS

Activated protein C (APC)

• How It Used to Help in MODS:

  • Anticoagulant: Inhibits factors Va and VIIIa → ↓ microthrombi in organs (a big factor in MODS).

  • Anti-inflammatory: Reduces cytokine production (like TNF-α, IL-6) → dampens the inflammatory cascade.

  • Cytoprotective: Preserves endothelial integrity and reduces apoptosis of vascular and immune cells.

• Inhibits inflammatory cytokines and coagulation factors

  • Helps with homeostasis

• G-CSF / GM-CSF for neutropenic patients * (esp. newborns)

• steroids / IVIG/etc in selected cases

what do we use as adjunctive immune therapy in MODS?