BY DR. KALPESH BORA GUIDED BY-DR. V.

V SHAHAPURKAR SIR

DEFINITION
Multiple

organ dysfunction syndrome (MODS),

previously known as multiple organ failure (MOF), is

altered organ function in an acutely ill patient requiring

medical intervention to achieve homeostasis.
It usually involves two or more organ systems. The use of "multiple organ failure" should be avoided

since that term was based upon physiologic parameters to

determine whether or not a particular organ was failing.

World War One Circulatory failure, hypovolemic shock World War Two Korean War Post-traumatic acute renal Viet Nam War insufficiency Post-traumatic acute respiratory insufficiency

1991 Multiple organ dysfunction syndrome

Seventys 70s syndrome

ORIGIN
Originally patients were classified as having sepsis or

the sepsis syndrome. This resulted in two concepts: Systemic inflammatory response syndrome (SIRS) and

Multiple organ dysfunction syndrome (MODS).

AIMS
Identify the patient at risk from developing MODS
give an account of possible preventative measures recognise progressive organ dysfunction as it is

occurring outline the treatment options available put surgical intervention into context describe the importance of good communication with the ICU team, and of early referral with a view to preventing organ failure becoming established

Causes
Sepsis

Trauma Shock due to any cause- cardiovascular/hemorrhagic Severe derangement in any particular organ system Other:

Burns Pancreatitis Massive blood transfusion Poisoning Eclampsia Acute CTDs, severe vasculitis Atrial myxoma, cholesterol emboli, SJS-TEN

Classification
Primary : Dysfunction is happened simultaneously in two or more organs due to primary disease. Secondary : Dysfunction happened in a organ, other organs sequentially happened dysfunction or failure.

INTRODUCTION
Multiple

Organ Dysfunction Syndrome (MODS) describes the progressive dysfunction and ultimate failure of organs in response to a noxious stimulus. This may be infection, trauma or inflammation, or some combination of these. MODS is common in the Intensive Care Unit (ICU), and carries a high mortality. It is easy to recognise when fully established, but more difficult to appreciate whilst it is developing, which is the time when prompt action may prevent further progression.

 Crucially, MODS is a syndrome not a diagnosis.

Identifying that a patient has MODS does not remove the requirement to diagnose and treat the underlying cause. Multiple Organ Dysfunction Syndrome is a specific term arising from the American College of Chest Physicians/Society of Critical Care Medicine

AETIOLOGY
The condition usually results from infection, injury

(accident, surgery), hypoperfusion and hypermetabolism.

The

primary

cause

triggers

an

uncontrolled

inflammatory response.
In operative and non-operative patients sepsis is the most

common cause.
Sepsis may result in septic shock.

 In the absence of infection a sepsis-like disorder is

termed systemic inflammatory response syndrome (SIRS).

Both SIRS and sepsis could ultimately progress to

multiple organ dysfunction syndrome. However, in

one-third of the patients no primary focus can be

found

ROLE OF INFECTION
Since infection has such a pivotal role in the development of MODS, it is important to consider possible sources. Primary infective causes that may lead to MODS include: primary pneumonia (community acquired). intra-abdominal surgical emergency (e.g. faecal peritonitis). meningococcal disease. gram positive toxic shock (Streptococcal or Staphylococcal). severe forms of food poisoning (e.g. Salmonella, E. coli 0157).

 Secondary infective causes (especially after surgery) that

may lead to MODS include:

postoperative pneumonia. Direct surgical complication (e.g. anastomotic leak,

abscess).
Other new infection (e.g. acalculous cholecystitis, urinary

tract infection [UTI]).

 Hospital-acquired (nosocomial) infections, especially in

the ICU, have a different pattern from those acquired in the community. Today, about 40% of ICU-acquired infections are Grampositive and a similar number are Gram-negative, with fungal infections comprising the next largest group. Staphylococcus aureus is the most common Grampositive organism, followed by Coagulase Negative Staphylococci and Enterococci.

 In the world the majority of Staphylococcus aureus are

now methicillin (flucloxacillin) resistant (MRSA), and an increasing number of Enterococci are becoming resistant to vancomycin (VRE). The most common Gram-negative is still Pseudomonas aeruginosa, with various coliforms also being seen frequently. It is recognised that the patient is usually the source of the bacteria, having become colonised whilst in hospital, especially if broad spectrum antibiotics have been given.

 The biggest source of bacteria in the body is the gut, and

colonisation of the upper gastrointestinal (GI) tract with bacteria is a well-recognised phenomenon in critically-ill patients.
All intubated patients suffer chronic low-grade aspiration

of pharyngeal secretions, which become contaminated

with bacteria from the GI tract and nasal sinuses.

Mechanism
Uncontrolled inflammatory response Microcirculatory hypo-perfusion Ischemia/reperfusion injury

Inflammation

Inflammatory cells
Inflammatory cytokines

MODS is the failure of the balance

Uncontrolled inflammatory response

Anti-inflammatory reaction IL-10, IL-4, TGF- IL-1ra ,Lipoxin Cell elimination

Pro-inflammatory reaction TNF-a, IL-1, IL-6, IFN TXA2, PAF Cell activation

CLASSIFICATION
Primary MODS describes a situation in which multiple

organ dysfunction is directly attributable to the initiating insult, as in the case of multiple trauma.
Secondary MODS describes a situation where the organ

dysfunction is not a direct result of the initial injury,

but

is

consequence

of

the

host

response,

characterised by a generalised activation of the inflammatory response in organs remote from the

initial insult.

Of course, both primary and secondary aspects of

MODS may exist in the same patient, but it is secondary MODS which has become such a familiar sight in modern ICUs.

Pathogenesis
Theories put forward: Gut hypothesis Endotoxin macrophage hypothesis Tissue hypoxia-microvascular hypothesis Integrated hypothesis

Gut hypothesis: The most popular theory to explain MODS in critically

ill patients is the gut hypothesis.

Due to splanchnic hypoperfusion and the subsequent

mucosal ischaemia there are structural changes and alterations in cellular function.

 This results in increased gut permeability, changed

immune

function

of

the

gut

and

increased

translocation of bacteria.
Hepatic dysfunction leads to toxins escaping into the

systemic circulation and activating an immune

response.
This results in tissue injury and organ dysfunction

 The gut also has the largest aggregation of lymphoid

tissue in the body (gut-associated lymphoid tissue, GALT), and may be a source of cytokine release even without translocation. Surface mucosal immunity, which is mediated by IgA, seems to operate in a common fashion in both the gut and the respiratory tree. Failure to protect the gut by failing to provide enteral feeding and ensuring adequate gut perfusion diminishes the effectiveness of the GALT and the gastrointestinal IgA, and also of the respiratory mucosal IgA, so potentially predisposing to respiratory infection.

Endotoxin macrophage theory: Gram-negative infections in MODS patients are relatively

common, hence endotoxins have been advanced as principal mediator in this disorder.
It is thought that following the initial event cytokines are

produced and released.

The pro-inflammatory mediators are:

Tumour

necrosis

factor-alpha
A2,

(TNF-),

interleukin-1,
platelet

interleukin-6,

thromboxane

prostacyclin,

activating factor, and nitric oxide

Tissue hypoxia-microvascular hypothesis: As a result of macro- and microvascular changes insufficient

supply of oxygen occurs.

Hypoxemia causes organ dysfunction and cell death.

Integrated hypothesis
Since in most cases no primary cause is found, the condition

could be part of a compromised homeostasis involving the previous mechanisms.

Infection/ injury

Inflammatory stimulator

Pro-inflammatory mediators released

Local inflammatory Systemic inflammatory cell cell activated activated (M (M ,PMN,VEC,) ,PMN,VEC,)

Tissue injury

Systemic Inflammatory Response Syndrome (SIRS) Definition

Anti-inflammatory reaction IL-10, IL-4, TGF- IL-1ra ,Lipoxin Cell eliminate

An uncontrolled inflammation process Pro-inflammatory signals exceed its normal domain or degree
Pro-inflammatory reaction TNF-a, IL-1, IL-6, IFN TXA2, PAF Cell Result inactivation end-organ damage

and multi-system

failure.

SIRS Clinical manifestations

Body temperature above above38 38 or less than 36.
Heart rate >90 beat/min. Respiration rate >20/min or PaCO2 <32 mmHg. WBC >12,000/mm >12,000/mm33 or <4000 cells/mm3, or >10% immature cells.

Definitions of systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and multiple organ dysfunction syndrome (American College of Chest Physicians, 1992)

Systemic inflammatory response syndrome Two or more of the following clinical signs of systemic response to endothelial inflammation: Temperature >38C or <36C Heart rate >90 beats/min

Sepsis Systemic response to infection manifested by two or more of the following: Temperature >38C or <36C

Raised heart rate >90/min Tachypnoea (respiratory rate >20 breaths/min or hyperventilation (PaCO2<4.25 kPa))
White blood cell count >12109/l or <4109/l or the presence of more than 10% immature neutrophils

Tachypnoea (respiratory rate >20 breaths/min or hyperventilation (PaCO2<4.25 kPa)) White blood cell count >12109/l or <4109/l or the presence of more than 10% immature neutrophils In the setting (or strong suspicion) of a known cause of endothelial inflammation such as:

Septic shock

Infection (bacteria, viruses, fungi, parasites, yeasts, or other organisms) Pancreatitis

Sepsis induced hypotension (systolic blood pressure <90 mm Hg or a reduction of 40 mm Hg from baseline) despite adequate fluid resuscitation Multiple organ dysfunction syndrome Presence of altered organ function in an acutely ill patient such that homoeostasis cannot be maintained without intervention

Ischaemia Multiple trauma and tissue injury Haemorrhagic shock Immune mediated organ injury Absence of any other known cause for such clinical abnormalities

Compensatory Anti-inflammatory Response Syndrome( CARS)

Definition

An uncontrolled Anti-inflammatory signals exceed its normal domain or degree Result in end-organ damage and multi-system failure. Pro-inflammatory reaction
TNF-a, IL-1, IL-6, IFN TXA2, PAF Cell activation

Anti-inflammatory reaction IL-10, IL-4, TGF- IL-1ra ,Lipoxin Cell eliminate anti-inflammation process

Immune paralysis

Infection/Injury

Uncontrolled inflammatory response SIRS CARS

Controlled inflammatory response

MODS

Infection/injur y controlled

Chronology of dysfunction
The progressive dysfunction of organ systems that

characterize MODS usually occurs in a predictable manner. During the first 72 hours of the original insult, respiratory failure commonly occurs. This is followed by
hepatic failure (5 to 7 days), gastrointestinal bleeding (10 to 15 days), and finally

renal failure (11 to 17 days)

DIAGNOSIS
The European Society of Intensive Care organized a

consensus meeting in 1994 to create the

"Sepsis-Related Organ Failure Assessment (SOFA)" score to describe and quantitate the degree of organ dysfunction in six organ systems. Using similar physiologic variables the Multiple Organ Dysfunction Score was developed.

SOFA SCORE
Organ parameters
Respiratory PaO2/FiO2
>400

1
</= 400

2
</= 300

3
</=200 with support

4
</=100 with support

Platelets * 10000/cumm Liver Bil mg/dl Hypotension

> 150
< 1.2 no

</=150 </=100 </=50

1.2-1.9 MAP < 70 mm hg 2.0-5.9
Dopamine <=5 or dobutamin any dose

</=20

6.0-11.9 >12
Dopamine >5 or epi <0.1 or norepi< 0.1 Dopamine >15 or epi >0.1 or norepi> 0.1

GCS Creatinine Urine output

15 <1.2

13-14

10-12

6-9

1.2-1.9 2.0-3.4

3.5-4.9 >5 <500ml/d <200ml/d

Four clinical phases have been suggested: 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. Moderate liver dysfunction and possible hematologic abnormalities. Stage 3 the patient develops shock with azotemia and acid-base disturbances. Significant coagulation abnormalities. Stage 4 the patient is vasopressor dependent and oliguric or anuric. Ischemic colitis and lactic acidosis follow.

SYSTEMS INVOLVED
There are various systems involves such as:1) Cardiovascular dysfunction:-

Cardiovascular dysfunction is a key component of MODS, and can be both a cause and a consequence. The key components of cardiovascular function are: cardiac function vascular tone vascular permeability.

Cardiac output is determined by: cardiac filling (preload) cardiac contractility heart rate vascular resistance (afterload). Blood pressure is generated by: cardiac output vascular resistance.

The pattern of cardiac dysfunction typically seen in sepsis and MODS is: Pathological vasodilatation Leading to hypotension and reduced cardiac filling, and a relative reduction in cardiac output. The reduced vascular tone also tends to increase cardiac output by reducing resistance to forward blood flow (afterload). The net effect of these opposing phenomena depends on the overall volume status. The mechanism for the vasodilatation is an increased production of nitric oxide by the vascular endothelium, resulting in vascular relaxation.

 Increased permeability, resulting in leakage of fluid into

the interstitium, oedema formation and hypovolaemia. In the lung the oedema contributes to impaired gas exchange. The hypovolaemia contributes to a fall in cardiac output. Many cytokines have direct myocardial depressing effects, resulting in impaired contractility and reduced stroke volume, so limiting the compensatory increase in cardiac output in response to a fall in vascular resistance. Heart rate is generally increased in response to the inflammatory mediators and increased sympathetic drive, resulting in an increase in cardiac output.

 The overall effect of these various factors depends upon

which predominate, on the volume status of the patient, and on the degree of pre-existing cardiac dysfunction which determines the cardiac reserve.
In a patient with a healthy heart who has been volume

resuscitated, the typical hyperdynamic pattern appears, in which there is a higher than normal cardiac output and a lower than normal vascular tone and blood pressure.

If blood pressure is inadequate there will be reduced perfusion of vital organs, manifested by:
confusion
a falling urine output

reduced myocardial perfusion dependent

predominantly upon systemic diastolic blood pressure.

If cardiac output is inadequate there will be signs of tissue

hypoxia due to reduced oxygen delivery

Oxygen consumption (VO2) is the difference between the amount of oxygen being despatched by the arterial supply and returning via the venous system. V02 - Hb x 1.39 x (Sa02 - Sv02) x 10 x CO If oxygen delivery is inadequate and tissue hypoxia develops, the signs of anaerobic metabolism will be present: worsening metabolic acidosis, with an increasingly negative base excess rising blood lactate level splanchnic ischaemia measured with a gastric tonometer (which measures CO2 production by the gastric mucosa, which increases as perfusion worsens).

2) Respiratory dysfunction :-Respiratory dysfunction is a key feature of MODS and arises for a number of reasons. Lung damage may be primary or secondary.Primary lung damage include:
pneumonia pulmonary contusion aspiration smoke inhalation.

Secondary lung damage occurs through the action of

inflammatory cytokines and activated white blood cells

from a distant source. Triggering events include:
pancreatitis abdominal sepsis massive blood transfusion.

 A key feature of lung dysfunction in MODS is that it is

acute, although there may be pre-existing lung disease. The term Acute Respiratory Distress Syndrome (ARDS) is used in this context but, just as with the terms relating to sepsis. The key principle that emerged was that an acute lung injury occurs in critically-ill patients in response to a number of different injuries. Conceptually, this is exactly the same principle as that which underpins MODS itself. Less severe damage would be known as Acute Lung Injury (ALI) and more severe damage as Acute Respiratory Distress Syndrome (ARDS).

The definitions of Acute Lung Injury and Adult (Acute) Respiratory Distress syndrome have several features in common:
An appropriate clinical setting with one or more recognised

risk factors
Bilateral diffuse fluffy infiltrates on the chest X-ray No clinical evidence of heart failure or fluid overload

(pulmonary artery occlusion pressure <18 mmHg), or chronic lung disease

Diffuse mottling of the lung fields characteristic of ARDS

 Apart from occurring as part of the end-organ damage

seen in MODS, ALI and ARDS may be triggered or exacerbated by overenthusiastic fluid resuscitation in patients where there is already pulmonary capillary damage with increased permeability and therefore a tendency to develop pulmonary oedema. Recently, there have been two more important conceptual advances. The first is that a considerable proportion of the lung injury seen in MODS patients with ALI or ARDS is probably caused by the sheer stresses imposed upon the lung by the mechanical ventilator. This has led to the term ventilator-induced lung injury (VILI).

 The second advance, briefly mentioned earlier, is the

realisation that the injured lung can contribute to the development or progression of MODS through the release of cytokines, even in the absence of pulmonary infection. A severe lung injury also has haemodynamic consequences. Pulmonary hypertension develops acutely and can be very severe, leading ultimately to right heart failure, with a rising central venous pressure and liver congestion. Forward blood flow through the injured lung also becomes impaired, and left ventricular filling and systemic blood flow fall.

 The combination of a falling cardiac output and a high

venous pressure results in impaired

arterio-venous

perfusion gradients across various organ beds, so further contributing to end-organ damage and the progression of MODS.
Finally, severe hypoxaemia due to ARDS also contributes to

the development of MODS by exacerbating tissue hypoxia.

Pressure-volume curve of the lung - demonstrating potential for lung damage with inadequate recruitment or overdistension

 The pressure-volume curve of the lung is sigmoid in shape.

At low total lung volume many alveoli are collapsed and the curve is flat. A large increase in pressure is required to generate a small change in lung volume, and so compliance is low. If the lung is ventilated at these volumes there is cyclical opening and closing of alveoli, causing damage. At high lung volumes the lung becomes over-distended and compliance is also poor. Ventilating here causes damage through overstretching alveoli.

 The straight portion of the curve reflects the range of

lung volumes where compliance is good and ventilation more efficient and less damaging. The two points where the curve changes shape are known as the lower and upper inflection points. The aim, therefore, is to stay between these two points throughout the respiratory cycle. Typically, this can be achieved by setting a positive endexpiratory pressure (PEEP) of 12-15 cm H20, which will approximate to the lower inflection point, and limiting tidal ventilation to 5-7 ml/kg, therefore remaining below the upper inflection point.

3) Aute renal dysfunction:Acute renal dysfunction and failure is a common feature of MODS. As with other organs, the kidney is a victim of the systemic process, but the pattern of renal impairment and subsequent failure and recovery owes much to the

specific anatomical and physiological characteristics of

the kidney.
Traditionally, acute renal failure is considered under the

headings pre-renal, renal and post-renal.

 Pre-renal failure implies inadequate blood flow, usually

due to hypovolaemia or hypotension. Renal failure implies direct renal damage. Post-renal failure implies obstruction to urine outflow.
In the context of MODS there are numbers of insults to

the kidney occurring at the same time rather than a single injury, and this classification is less useful. The haemodynamic changes contribute to reduced perfusion and local hypoxia, which is exacerbated by hypoxaemia secondary to the lung injury.

 Conditions of borderline hypoxia already exist in the

renal medulla, due to the countercurrent anatomy of

the kidney, making it particularly vulnerable to further insult.
The generalised inflammatory response also results in

direct kidney damage by cytokines and activated white blood cells.

Finally, these processes may exacerbate the effects of

nephrotoxic drugs.

The renal response to injury consists of three phases: Oliguria - conservation of salt and water by a reduction in urine output. Urea and creatinine levels rise. At this stage, urine output can still be restored if the patient is resuscitated successfully. Anuria - renal failure becomes established, urine output becomes minimal or ceases for a period of days or weeks even if renal blood flow is restored and the initiating insult resolved. During this period renal support techniques are required.

 Recovery - urine output returns, but initial quality is poor

and there is often a period of polyuria before full recovery of function occurs. Occasionally, there is no anuric period,

and the patient suffers polyuric renal failure only.

This may still be associated with marked metabolic and

biochemical abnormalities, but management of fluid balance remains possible with appropriate fluid replacement regimens.

The major pathological consequences of acute renal failure are: rising urea and creatinine. rising potassium. Worsening metabolic acidosis, usually associated with a normal lactate. Fluid balance abnormalities (depending upon the cause of the renal failure), followed by a tendency to become fluid overloaded easily if anuric, and fluid depleted if polyuric. The impact of acute renal failure upon the outcome of patients with MODS is often debated, since the mortality of this group of patients is so high; of the order of 5070%.

4) Acute liver dysfunction:- The liver is fundamental to many metabolic and immune functions, and has a rich blood supply via

the hepatic artery and the portal vein.

Not surprisingly, it may well have a pivotal role in the development of MODS, although research into the liver in this context has been

relatively lacking.
Traditional liver function tests (liver enzymes, bilirubin, albumin and clotting) are often non-specifically deranged in critically-ill patients,

and give little information about acute changes in liver function.

Transaminases may be dramatically increased after episodes of severe ischaemia or shock; so called shock liver.

More specific tests of dynamic liver function are available for research purposes, and these include:
measurements of liver blood flow using a hepatic vein catheter

indocyanine green clearance, which measures liver blood flow

and secretory function

arterial ketone body ratio, which gives a marker of the redox

state of the liver

metabolism of an injection of lignocaine to

monoethylglycinexylidide (MEGX), which gives a measure of

liver blood flow and cytochrome P450 system function.

 Although none of these is suitable for routine use,

they have revealed that there is often very severe acute liver dysfunction in patients with MODS which is not apparent from conventional tests, and that the degree of liver dysfunction may predict outcome.
If bacteria, endotoxin or cytokines are released into the

portal blood from a leaky gut, an immune response in the liver results.
What subsequent role this might have in causing the

systemic response seen in MODS is still unclear, but this mechanism has often been suggested as one possible stimulus for the development of MODS as part of the gutorigin of MODS theory.

GIT DYSFUNCTION
Apart from a possible role in the genesis of MODS, the

gut is directly involved in two more straightforward ways, both of which might be regarded as being gutfailure, i.e.: failure to tolerate enteral feeding stress ulceration and gastrointestinal bleeding. Failure to tolerate enteral feeding Critically-ill patients all require tube feeding when they are intubated and ventilated, and may be difficult to feed enterally.

Haematological dysfunction
Haematological dysfunction is an area that is readily overlooked, but

abnormalities are commonplace in the patient with MODS. The patterns seen are usually due to systemic consumption of blood components or bone marrow depression, i.e.:
Peripheral consumption (disseminated intravascular coagulation, DIC)

due to activation of the coagulation pathways as part of the inflammatory response seen in MODS features include prolonged clotting, low platelets, low fibrinogen, low antithrombin III and low protein C, with bleeding and anaemia in severe cases.

 Bone marrow depression features include anaemia, a very

low white cell count in the face of severe infection, and a low platelet count.
Both syndromes, which often occur at the same time,

require support with blood products if severe. Moreover,

microvascular coagulation in DIC impairs perfusion at the capillary level and contributes to organ hypoxia and dysfunction seen with MODS

Cerebral dysfunction
Cerebral dysfunction is very difficult to quantify and assess

in critically-ill patients. In the acute phases of severe illness patients become obtunded, often for a variety of reasons.
Most common are the global effects of hypoxia and

hypotension, but there may be more subtle changes

affecting extra-mitochondrial enzyme systems and nerve

conduction.

 Any patient who has depressed consciousness in this

context is severely unwell, and should have his/her airway protected as soon as possible.
Once intubated and sedated, patients with MODS become

much

more

difficult

to

assess,

but

non-specific

encephalopathy as well as drug effects are commonplace,

and may take considerable time to resolve.

 Patients with prolonged MODS also exhibit peripheral

neuropathies and myopathies. These may be subclinical,

detectable only on neurophysiological testing, or profound,

resulting in severe and prolonged weakness or even complete paralysis.
The clinical picture is very similar to that of the Guillian-

Barr Syndrome, and peripheral demyelination and axonal damage are sometimes seen, as well as muscle wasting and necrosis.

 The exact cause is unclear, but immunological factors,

microvascular occlusion and effects of drugs, especially non-depolarising neuromuscular blockers (and

denervation in the case of muscle damage) have all been implicated.

TREATMENT
Having recognised that a patient is developing MODS,

the first principle is to resuscitate and make safe. This means referring to the ICU and usually:
establishing good intravenous access instituting invasive arterial monitoring (central venous

catheter + pulmonary artery catheter)

intubating and ventilating

 providing

cardiovascular support with fluids, vasopressors and inotropes guided by invasive haemodynamic monitoring. Unfortunately, no single treatment for MODS will reverse the associated high mortality. Survival is more likely when the cause of MODS can be found and eliminated. Further measures include: infection screen taking blood, sputum and urine cultures

 full

haematological (including clotting) and biochemical screen commencing broad-spectrum antibiotics providing renal and nutritional support as necessary identifying the source of the sepsis that has led to MODS and treating it. If there is a surgical cause, this should be remedied surgically as soon as the patient has been stabilised, since there is unlikely to be improvement otherwise.

 Resuscitate the patient from septic shock using

supportive measures to correct hypoxia, hypotension, and impaired tissue oxygenation. Identify the source of infection and treat with antimicrobial therapy, surgery, or both. Maintain adequate organ system function guided by cardiovascular monitoring and interrupt the pathogenesis of multiorgan system dysfunction.

Features of therapy
Largely supportive: Etiology control Maintenance of oxygen transport Use of activated protein C Corticosteroids Metabolic support Organ support

Etiology control
Infection - antibiotics
Trauma - wound care/amputation if required Abscess: - drainage

Burns skin grafting

Oxygen support
Objective is to achieve supramarginal oxygen level in

the tissues so that the increased needs are fulfilled

Maintaining a high oxygen content of 70mm hg Oxygen saturation over 90%

Hemoglobin at 11g/dl

------------- a good indicator is the serum lactate levels.

Corticosteroids
Intravenous corticosteroids (hydrocortisone 200-

300mg/day, for 7days in three or four divided doses or by continuous infusion) are recommended inpatients with septic shock who, despite adequate fluid replacement, require vasopressor therapy to maintain adequate blood pressure.
----- surviving sepsis guidelines SCCM

2004

Metabolic support
Calorie around 30-50 cal/kg/day with no more than 5

gm/kg/day of glucose
Increased carbohydrate causes excessive lipolysis and

CO2 production

Fat emulsion (W-6 PUFA) not more than 0.5-1

gm/kg/day Proteins 1.5-2gm/kg/day Vitamins, minerals and trace elements

 Total parenteral nutrition (TPN) is often used in the ICU

since it provides a sure way of delivering nutrition to patients immediately.

Unfortunately, however seductive the use of TPN might

be, it does not appear beneficial compared with no

feeding at all for at least 10 days, has a number of harmful effects, and is very expensive.
TPN is associated with:

 increased

infection

rate,

because

of

direct

immunosuppressive effects due to the fat preparations used, and due to the requirement for central venous access
gut atrophy leading to increased gut permeability, since

enterocytes receive much of their nutrition from the

contents of the gut lumen and villi atrophy with disuse.

And lastly, rather most importantly-Organ support

Lungs -Mechanical ventilation
Kidneys -Renal replacement therapy CVS -Dopamine, dobutamine, IABP

CNS supportive care

Liver supportive care, liver assist devices Hematology - transfusions

SUMMARY
MODS is the extreme end of an infective or

inflammatory process. The mortality is high, and MODS is a major cause of death after surgery. All organ systems are involved. Early recognition and treatment in an ICU are essential. This is often an expensive and timeconsuming process. Successful care is multidisciplinary in nature.

At the end of the day

We should always be able to identify the worsening

features at the earliest and intervene We should not have a hopeless attitude towards patients having various organ involvement Critical care can be truly rewarding if the principles are followed diligently.. -------------------

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