MULTIPLE ORGAN DYSFUNCTION

SYNDROME BY

DR.AKINBI OLUBAYODE.O

INTRODUCTION Multiple organ dysfunction

syndrome (MODS), also known as multiple organ failure (MOF), total organ failure (TOF) or multisystem organ failure (MSOF)

MODS contributes to about 50% of ICU deaths

Failure of 2 to 3 organs is associated with 90% mortality.

Organ recovery is frequently the rule in surviving patients without pre-existing organ disease

DEFINITION: MODS is the presence of altered organ function in acutely ill patients such that homeostasis cannot be maintained without intervention. It usually involves two or more organ systems.SIRS is a systemic inflammatory response to a variety of insults including infection, ischemia, infarction, and injury, it leads to disorders of microcirculation, organ perfusion and finally secondary organ dysfunction.

HIGH RISK PATIENTS Patients with infection Shock episode associated with a rupture

aneurysm, acute pancreatitis, sepsis, burns or surgical operation.

Patients >65 years of age because of there decreased organ reserve and presence of co-morbidities

Severe trauma, multiple injury, massive blood loss, hypovolemic shock and infection.

ETIOLOGY 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

CLASSIFICATION OF MODS1. Immediate type(primary):

Dysfunction/Failure occurring simultaneously in two or more organs due to primary disease.

2. Delayed type(secondary): Dysfunction occurred in one organ other organs sequentially fail.

3. Accumulation type: Dysfunction is cause by chronic disease. It is irreversible

PATHOGENESIS Organ dysfunction in a critically ill patient can be described in one of two ways: As the clinical intervention that was

employed to support the failing organ system (mechanical ventilation, hemodialysis, inotropic or vasopressor agents, parenteral nutrition etc), or

As the acute physiologic derangement that made such support necessary.

ORGAN SPECIFIC MANIFESTATION

GI dysfunction Hepatobiliary dysfunction Pulmonary dysfunction Renal dysfunction Cardiovascular dysfunction Coagulation system dysfunction others

GASTROINTESTINAL DYSFUNCTION

Gastrointestinal dysfunction in critical illness likely results from the interacting effects of reduced regional blood flow, impaired motility, and alterations in the normal microbial flora.

In the past, upper gastrointestinal bleeding or stress ulceration was the most common manifestation of gut dysfunction;

This complication has become uncommon with improvements in hemodynamic support, earlier diagnosis of infection, and the appropriate use of effective prophylaxis

Intolerance of enteral feeding, reflected in bloating and diarrhea is another manifestation of gut dysfunction.

However, in contrast to other organ systems, simple clinical measures of gut dysfunction are not readily available.

Gastrointestinal Dysfunction

Hypoperfusion Ischemia of the gut

Decreased integrity of the gut lining

Decreased peristalsis

Translocation of normal GI bacteria into systemic circulation

Colonization of normal GI flora up into the orpharynx

Systemic infection and SIRS

Aspiration of bacteria and initiation of a inflammatory response in the lung

HEPATOBILIARY DYSFUNCTION Hepatic dysfunction in MODS is reflected in

hyperbilirubinemia and cholestasis, rather than in biochemical evidence of hepatocellular injury or synthetic dysfunction.

A stereotypical pattern of altered hepatic protein synthesis - the acute phase response - typically accompanies MODS as a non-specific manifestation of systemic inflammation.

Serum levels of C reactive protein and alpha-1 anti-trypsin are elevated as part of the acute phase response, whereas levels of albumin, a negative acute phase reactant, are depressed.

Hepatobiliary Dysfunction

Hypoperfusion Ischemia of the liver and gallbladder

ischemic hepatitis acalculous cholecystitis

Jaundice

serum transaminase

serum bilirubin

Right upper pain and tenderness

Abdominal distention

Unexplained fever

Loss of bowel sounds

PULMONARY DYSFUNCTION The characteristic abnormality of the lung in

MODS is a failure of normal gas exchange, reflected predominantly in arterial hypoxemia.

Multiple pathologic factors contribute to impaired gas exchange.

Early in the course of lung injury, atelectasis and intravascular thrombosis or altered regional flow contribute to ventilation/perfusion mismatch, while increased capillary permeability leads to alveolar flooding and an increased diffusion distance for oxygen.

Regional injury resulting from infection or trauma contributes to compromised lung function. 

With the institution of ventilatory support, lung injury can be aggravated through what has been termed volutrauma and barotrauma, leading to further atelectasis in dependent lung zones, and cyst formation in the anti-dependent zones.

Finally, the process of tissue repair, initiated with

the influx of inflammatory cells into the injured lung, results in fibrosis and hyaline membrane formation, the cardinal pathologic features of late ARDS.

RENAL DYSFUNCTION Renal dysfunction in MODS is reflected in

impairment of normal selective excretory function, initially in oliguria despite adequate intravascular volume, but later in a rising creatinine level, and fluid and electrolyte derangements of sufficient magnitude that dialysis is required.

Its causes are both pre-renal and renal. Reduced renal blood flow secondary to systemic hypotension, altered regional perfusion, or increased intra-abdominal pressure is an early risk factor;

Evolution of the disorder is compounded by pre-existing physiologic deficit and the effects of nephrotoxic drugs. Obstructive causes must be considered and ruled out. 

 As is the case for lung injury, ICU interventions contribute to the evolution of the syndrome: vasopressor agents cause further reductions in renal blood flow, while potentially nephrotoxic drugs are a key part of the anti-infective arsenal used in the ICU.

Renal Dysfunction

Hypoperfusion

And

Renal toxic drugs

Ischemia of the Kidney

Azotemia

Creatinine clearance

Fluid and electrolyte imbalances

Fluid volume overload

Renal Function

CARDIOVASCULAR DYSFUNCTION

The acute cardiovascular derangements of MODS consist of five features: A generalized reduction in peripheral vascular tone,

mediated largely through the local vasodilatory activity of nitric oxide

A generalized increase in capillary permeability producing diffuse capillary leak and edema, and contributing to further dysfunction in other organ systems

Alterations in regional blood flow to specific organ beds

Microvascular plugging and stasis, resulting from occlusion of the microvasculature by abnormally rigid erythrocytes and leukocytes, and resulting in arteriovenous shunting that contributes to a high mixed venous saturation

Myocardial depression, affecting the right side of the heart in particular

It is readily apparent that these abnormalities predispose to impaired oxygen delivery, and therefore contribute to the injury of other organ systems.

Cardiovascular Dysfunction

Initial response Myocardial

depression Right atrial pressure SVR Venous capacitance VO2 CO HR

Late response Ventricular dilatation Diastolic

compliance contractile

function CO Ability to maintain

BP without vasopressors

HEMATOLOGY DYSFUNCTION

Leucocytosis is an adaptive response to a variety of acute stresses and therefore commonly present, although not truly a manifestation of organ dysfunction.

Similarly a mild anemia resulting from both bone marrow suppression and iatrogenic blood-taking is common.

However the most widely cited manifestation of dysfunction of the hematologic system in MODS is thrombocytopenia, in its most extreme form resulting in disseminated intravascular coagulation (DIC).

Failure of the coagulation system is manifested as DIC.

Results in simultaneous microvascular clotting and hemorrhage in organ systems because of the depletion of clotting factors.

Like other manifestations of MODS, the causes of thrombocytopenia in critical illness are mainly - heparin-induced thrombocytopenia, intravascular consumption, and reduced production to name a few.

NEUROLOGIC DYSFUNCTION

An altered level of consciousness, reflected in a reduction in the Glasgow Coma Score, is the most readily recognizable manifestation of the neurologic dysfunction of MODS.

Its causes are multiple, including the iatrogenic effects of sedatives and analgesics, metabolic alterations, subclinical cerebral edema and reduced cerebral perfusion pressure, and, perhaps, micro-abscesses in the brain. A peripheral neuropathy - the so-called ‘critical illness polyneuropathy’ - is commonly present, though harder to measure.

Central Nervous System

Clinical Lab

Altered level of consciousnessImpaired mentationConfusionDeliriumPsychosis

Bispectral EEG monitoring

IMMUNOLOGIC DYSFUNCTION

Multiple abnormalities of non-specific and specific immune function are described in the critically ill patient, including impaired delayed type hypersensitivity responsiveness, altered production of antibodies, and a complex spectrum of abnormalities in the regulation of lymphocyte responses

The most readily evident, and clinically relevant manifestation of altered immunity in MODS is the development of nosocomial ICU-acquired infection, caused by relatively a virulent organisms.

The characteristic flora of ICU-acquired infection in MODS includes coagulase-negative Staphylococci,Enterococci, Candida, and Pseudomonas.

ENDOCRINE/METABOLIC DYSFUNCTION

Multiple metabolic and endocrine abnormalities are evident during MODS, although they are less well-characterized, Hyperglycemia and relative insulin resistance is both common and readily detected.

Less accessible abnormalities include the sick euthyroid syndrome, and relative adrenal insufficiency.

The latter has recently gained prominence as a promising therapeutic target for the patient with prolonged inflammation and organ dysfunction.

Metabolic/NutritionalClinical LabDecreased lean body massMuscle wastingSevere weight loss

Negative nitrogen balanceHyperglycemiaHypertriglyceridemiaIncreased serum lactateDecreased serum albumin,serum transferrin,prealbuminDecreased retinol-binding protein

MULTIPLE ORGAN DYSFUNCTION (MOD) SCORE

an system 0 1 2 3 4Respiratorya

(PO2/FIO2 Ratio)

> 300 226–300 151–225 76–150 ≤ 75

Renalb

(Serum Creatinine)

≤ 100 101–200 201–350 351–500 > 500

Hepaticc

(Serum Bilirubin)

≤ 20 21–60 61–120 121–240 > 240

Cardiovasculard

(R/P Ratio) ≤ 10.0 10.1–15.0 15.1–20.0 20.1–30.0 > 30.0Hematologice

(Platelet count)

> 120 81–120 51–80 21–50 ≤ 20

Neurologicf

(Glasgow Coma Score)

15 13–14 10–12 7–9 ≤ 6

Stage 1 the patient has increased volume requirements and mild respiratory alkalosis which is accompanied by oliguria, hyperglycemia and increased insulin requirements.

Stage 2 the patient is tachypneic, hypocapnic and hypoxemic; develops moderate liver dysfunction and possible hematologic abnormalities.

Stage 3 the patient develops shock with azotemia and acid-base disturbances; has significant coagulation abnormalities.

Stage 4 the patient is vasopressor dependent and oliguric or anuric; subsequently develops ischemic colitis and lactic acidosis.

The PO2/FIO2 ratio is calculated without reference to the use or mode of mechanical ventilation, and without reference to the use or level of PEEP.

The serum creatinine level is measured in μmol/liter, without reference to the use of dialysis.

The serum bilirubin level is measured in μmol/liter.

The R/P ratio is calculated as the product of the heart rate and right atrial (central venous) pressure, divided by the mean arterial pressure:

The platelet count is measured in platelets/mL 10-3

The Glasgow Coma Score is preferably calculated by the patient's nurse, and is scored conservatively (for the patient receiving sedation or muscle relaxants, normal function is assumed unless there is evidence of intrinsically altered mentation).

The relationship between MOD score and mortality of patient

MODS score mortality(%)0 0

9~12 2513~16 5017~20 75

>20 100

MANAGEMENT At present there is no agent that can reverse

the established organ failure. Therapy therefore is limited to prevention and supportive care

The principle are Decrease the severity of the risk factor Prevention of inflammation: drainage and

antibiotics Appropriate resuscitation and control of

infection Avoid unsuitable operation Treat the dysfunction organ and malnutrition

Correction of ischemia Interruption of pathological reaction:

hemofiltration Stabilization of internal environment:

water, electrolyte, acid base imbalance. Regulation of immunity: cellular and

humoral

The prevention of MODS in clinical illness

Target system Convincing evidence Controversial or investigational

Lung Pressure or volume limited ventilation to minimize barotrauma and volutrauma

Liquid ventilation, non-physiologic modes of ventilation (high frequency, oscillation)

Cardiovascular Restrict transfusion of packed red cells when hemoglobin is > 70

Supranormal oxygen delivery; non-crystalloid fluids; SwanGanz catheterization

Renal Avoidance of nephrotoxins

Continuous veno-venous hemofiltration

Gastrointestinal Stress ulcer prophylaxis with H2 blockers rather than sucralfate

Gastric tonometry

Enteral nutritionHematologic DVT prophylaxis Anticoagulant

therapies such as anti-thrombin III

Immunologic SDD (Selective Decontamination of the Digestive Tract)

Anti-cytokine and other mediator-targeted therapies (9)

Endocrine Corticosteroids in late sepsis

COMPLICATIONS Adult respiratory distress syndrome

(ARDS ) Disseminated Intravascular

Coagulation( DIC) Acute Renal failure (ARF) Intestinal bleeding Liver failure Central Nervous System dysfunction Heart failure Death

CONCLUSION Multiple organ failure is the commonest

cause of death in the intensive care unit setting.

There are numerous precipitating factors including sepsis, trauma and pancreatitis.

The resulting tissue hypoxia, exaggerated inflammatory response and generation of free oxygen radicals leads to tissue damage and organ dysfunction.

No definitive treatment exists despite considerable efforts to find a ‘magic bullet’.

Management still revolves around support of organ function and prevention of iatrogenic complications until recovery occurs.

An increasing emphasis is being placed on prevention of organ dysfunction, including maintenance of tissue oxygenation, nutrition and infection control.