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Multiple Organ Failure

Multiple Organ Failure: Pathophysiology and clinical features.
Name: Ebtisam Hanshool Algethami
Student number: 160553231 Module: WHR7010 Date: December 3rd, 2018 Word count: 2000
Dr.Parjam Zolfaghari4000020000Supervisor:
Dr.Parjam Zolfaghari
Multiple Organ Dysfunction Syndrome (MODS) is reported to be the main cause of mortality in Surgical Intensive Care Units (SICU) of most healthcare facilities.4 The study of Mizock found the prevalence of MODS among patients admitted in the Intensive Care Unit (ICU) due to trauma was 47%.4 On the other hand, based on two common diagnostic criteria established by Proulx (1996) and Goldstein (2005), the study of Villeneuve, et al. found the incidence of MODS among children admitted at the Paediatric Intensive Care Unit (PICU) was 21.4% and 37.3% respectively.1 MODS is caused by an overwhelming and excessive systemic inflammatory response to foreign stimuli (infections, antibodies), which result in severe body tissue damages and therefore, functional failure in more than one organ of the body.3 The implication is that patients with severe traumatic injury, sepsis and hypovolemic shocks are at a high risk of experiencing MODS.3
This paper examines and provides a discussion of the causes and epidemiology of multiple organ dysfunction syndromes (MODS). In addition, the paper will also present a discussion on the clinical manifestation of MODS among patients who are admitted to ICUs. Ultimately, the paper will examine and provide a discussion on the pathophysiological effects of MODS among patients who are admitted in ICU.

Definition of MODS
MODS manifests itself as an immunodepressed condition, which results in the reduced functioning of more than one organs of the body.1 MODS is a condition that develops as a result of the patient experiencing severe traumatic injury, shock, sepsis, eclampsia, and ischaemia.3 Mizock defines MODS as a condition in which more than one body organ is dysfunctional such that the body’s self-control mechanism (homeostasis) cannot be effectively maintained without some form of clinical interventions.4 On the other hand, the definition by John Marshall states that MODS is a condition that develops as a reversible physiologic derangement with respect to two or more body organs that were not associated with the initial disorder, which prompted admission into the intensive care unit.2
Causes of MODS
The main cause of MODS is the occurrence of systemic inflammatory response, which is stimulated by foreign antibodies that emanate as a result of certain physiological conditions such as shock, sepsis and traumatic injuries.5 The acute inflammatory responses to foreign stimuli generate excessive insults, which damage the body tissues, consequently leading to loss of body function5. The implication is that MODS is caused by the body’s immune system failure to localize the stated inflammation.2
In addition, MODS is also caused by the presence or occurrence of any infection that results in tissue damages such as severe traumatic injury, burns, sepsis, ischaemia, eclampsia, and pancreatitis.6 The stated diseases tend to cause multi-organ failure due to the fact that the damaged body tissues tend to initiate a series of body reactions leading to acute inflammatory responses and functional failure in various organs of the body.7 Finally, certain chemical therapy, extracorporeal cardiac circulation and blood transfusions also tend to cause MODS among patients admitted to ICUs.1 The stated chemical therapy and blood transfusion result in MODS due to the fact that introduction of foreign antibodies is likely to prompt an initiation of the body’s inflammatory response system, which causes severe tissue damages and failure of more than one body organs.8
Epidemiology of MODS
The epidemiological incidences of MODS vary considerably depending on the specific diagnostic criteria that have been employed to undertake a particular study.1 The study of Mizock found that 47% of patients with traumatic injuries admitted at SICU had MODS.4 The same study found that patients with multi-organ failure had 3.9 times higher probability of needing some form of assistance.4 On the other hand, using Proulx and Goldstein MODS diagnostic criteria, Villeneuve, et al. found that the epidemiological incidence of the condition among children admitted at PICU was 21.4% and 37.3% respectively.1 Table 1 and chart 1 presents a summary of the epidemiological incidence of MODS based on the study outcomes of Villeneuve, et al.

Table 1: Epidemiological Incidence of MODS based on the Study of Villeneuve1
Proulx Diagnostic Criteria Goldstein Diagnostic Criteria
Reported Incidence of MODS 21.40% 37.30%
Chart 1: Epidemiological Incidence of MODS based on the Study of Villeneuve1

The incidence of mortality due to MODS tends to vary with the number of body organs that have experienced failure.2 The study of Marshall found that patients with more than 5 organ failure had more than 80% chance of losing their lives.2 Table 2 presents a summary of the findings by Marshall.2
Table 2: Incidence (Prognosis) of MODS2
Number of Organ Failure Mortality (%)
0 ; 10
1 0-30
2 20-50
3 40-80
4 60-100
? 5 ; 80
The results depicted in table 2 indicate that the incidence of mortality among patients with MODS tends to increase with the number of body organ failure.

Clinical Manifestation of MODS
Clinical manifestations of the symptoms of MODS tend to be evident from an assessment of the main physiologic functional failures.2 The most common clinical manifestation of MODS is a failure in the patient’s respiratory patterns.9 Specifically, respiratory failure among patients with MODS tends to result in dyspnea, hypoxemia and abnormal oxygen indices.10
In addition, the other clinical manifestation of MODS is a gastrointestinal failure where the body develops an intolerance to specific enteral feeding and paralytic ileus.7 Moreover, gastrointestinal failure is also evident when the patient diagnosed with MODS experiences bleeding in both the lower and upper abdomen.7 Gastrointestinal failure in patients with MODS also tends to result in diarrhoea, reduced sound in the bowel as well as an overgrowth of bacteria in the patient’s stool.6
Clinical manifestation of MODS is also evident when there is a higher level of serum bilirubin that is produced in the liver.5 Furthermore, increased incidences of jaundice and production of the substantially high amount of enzymes in the liver is also another clinical manifestation of MODS.2 Liver failure among patients diagnosed with MODS also tends to result in increased production of serum ammonia.4
Marshall observes that pain or tenderness in the gallbladder coupled with incidences of distention in the abdomen also provides a clinical manifestation of multiple organ failure syndromes.2 In addition, reduction in the patient body mass, muscles, weight loss, and incidences of hyperglycemia also tend to provide a substantive clinical manifestation of MODS among patients suffering from traumatic injuries.1 Furthermore, with respect to renal failure, the clinical manifestation of MODS is evident when there is increased production levels of serum creatinine coupled with increased incidences of acute tubular necrosis in patients.3
Increased Systemic Vascular Resistance (SVR) and Right Atrial Pressure (RAP) due to cardiovascular failure are also key clinical manifestation of MODS among patients with traumatic injury.2
On the other hand, in terms of dysfunctional failure in the central nervous system, MODS also manifests itself when the patient experiences loss of conscious, high fever and lethargy due to alteration in his/her CNS.1 Finally, incidences of decreased counts of lymphocyte cells and intravascular coagulation among patients diagnosed with traumatic injury also provide key clinical manifestation of MODS.2
Pathophysiology of MODS
The pathophysiologic assessment and description of multiple organ failure is undertaken based on the six basic functional organ systems, which relate to the cardiovascular system, renal system, respiratory system, hematologic system, hepatic system, and neurologic system.2 Marshall uses MODS score system to define the severity and extent of multiple organ failure based on the stated six key organ system.2 Table 3 presents a summary of MODS score based on the stated study.

Table 3: Multiple Organ Dysfunction Syndrome (MODS) Score based on Marshall2
Organ System 0 1 2 3 4
Respiratory System (PO2/FIO2 Ratio) ; 300 226-300 151-225 76-150 ?75
Renal System (Serum Creatinine) ?100 101-200 201-350 351-500 ; 500
Hepatic System (Serum Bilirubin) ? 20 21-60 61-120 121-240 ; 240
Cardiovascular System (R/P Ratio) ? 10 10.1-15.0 15.1-20 20.1-30 ; 30
Hematologic System (Platelet Count) ; 120 81-120 51-80 21-50 ? 20
Dysfunction in the Immune Response System
The most critical pathophysiological mechanism of MODS is a disordered immune system in patients that have experienced hypovolemic shock, trauma and sepsis.3 The occurrence of the stated conditions tends to stimulate the body’s systemic inflammatory response due to the presence of foreign antibodies, which consequently exacerbate the production of insults (shocks) that ruptures the body’s tissues.4 The damage to the body’s tissues is likely to result in multiple organ failure due to loss of homeostasis between the stated systemic inflammation and the corresponding anti-inflammatory response to the foreign stimuli.4 The extent of the stated systemic inflammatory response depends on a variety of factors such as the patient age, nutritional status, existence of certain comorbid diseases and the genetic orientations of the patients.2
Dysfunction in the Respiratory System
The main pathophysiologic dysfunction in the patient respiratory system is evident when there is a failure in gas exchange within the patient lungs.2 This pathophysiological dysfunction tends to manifest itself in the form of arterial hypoxemia.10 Intravascular thrombosis and atelectasis due to lung failure are also likely to contribute to increased incidences of perfusion mismatch within the patient respiratory system.2
Dysfunction in the Renal System
Dysfunction in the patient renal system due to trauma and hypovolemic shock is initially expected to impair the body’s excretory function as is evident with production of insufficient urine (oliguria).2 However, dysfunction in the renal system tends to be severe later on when increased levels of creatinine and other fluids are produced in the kidney to the extent that dialysis is recommended to facilitate the patient’s renal system.2 Altered perfusion and reduced blood flow in the renal system are also key pathophysiological dysfunction among patients with MODS.9 However, Mizock argues that the administration of vasopressors and nephrotoxic drugs could also contribute to decreased blood flow in the patient renal system.4
Dysfunction in the Cardiovascular System
The pathophysiological dysfunctions present in the cardiovascular system due to multiple organ failure is manifested with significant alterations in the flow of blood to other organs of the body.2 In addition, cardiovascular failure is also evident when patients admitted with traumatic injury tend to experience increased capillary permeability, which results in capillary leaks, oedema and dysfunctions in other organs of the body.2 The dysfunction in other body organs as a result of cardiovascular failure is mainly caused by impairment in the circulation and delivery of oxygen in the other parts of the body.1
Dysfunction in Hepatic System
In patients with MODS, gastrointestinal failure is evident with the production of a high amount of serum bilirubin and cholestasis.2 In addition, gastrointestinal dysfunction is also manifested when there is intolerance in enteral feeding (bloating and diarrhoea) among critically ill and traumatic patients.1 However, Marshall argues that incidences of gastrointestinal bleeding especially in the upper abdomen have significantly declined due to enhancements of hemodynamic support systems and use of prophylaxis in critically ill patients.2
Dysfunction in the Neurologic System
Critically ill patients with multiple organ failure tend to experience an alteration in their levels of consciousness.1 Moreover, dysfunction in the neurologic system is also associated with decreased cerebral perfusion among patients with traumatic injury.2 Neuropathy is also associated with a dysfunctional neurologic system despite the fact that the stated condition is difficult to measure and diagnose.2
Dysfunction in the Hematologic System
The most common pathophysiologic dysfunction in patient’s hematologic system is the condition of thrombocytopenia among critically ill patients.2 Furthermore, the condition of anemia due to suppression in the patient’s bone marrow and iatrogenic blood transfusion is also a common pathophysiologic dysfunction in the hematologic system.1 However, Marshall argues that due to its adaptive functional response among critically ill patients, leukocytosis is not generally considered as a dysfunction in the hematologic system.2
The main objective of this paper was to examine the epidemiology, clinical manifestation and pathophysiology of MODS, which is a condition that results in more than one organ failure especially among patients diagnosed with sepsis, hypovolemic shock and trauma. The paper acknowledges that the main cause of MODS is the occurrence of systemic inflammatory response that is induced by foreign stimuli. The stated systemic inflammatory response has the adverse effect of aggravating damage to body tissues and consequently multiple organ failure. The paper acknowledges that the reported epidemiological incidences of MODS among patients admitted at a SICU are approximately 47%. On the other hand, the main clinical manifestations of multiple organ failure include problems with the patient respiratory system as evidenced by abnormal oxygen indices coupled with bleeding in both the lower and upper abdomen. Furthermore, production of high levels of serum bilirubin and occasional pain in the gallbladder is a key clinical manifestation of multiple organ failure. Ultimately, the paper concludes that the main pathophysiologic manifestations of multiple organ dysfunction syndromes (MODS) are evident based on the outcome of assessment related to the six main functional system disorders; cardiovascular, renal, hepatic, hematologic, respiratory, and neurologic systems.

References1-Villeneuve A, Joyal JS, Proulx F, et al. Multiple organ dysfunction syndrome in critically ill children: clinical value of two lists of diagnostic criteria. Annals of Intensive Care. 2016; 6(1): 40-47.
2-Marshall JC. The multiple organ dysfunction syndrome. Critical Care Medicine. 2015; 23(1): 1638-1652.

3-Vincent JL, Moreno, R. Clinical review: scoring system in the critically ill. Journal of Critical Care. 2010; 14(2): 207-216.

4-Mizock B. The multiple organ dysfunction syndrome. DM Journal. 2009; 2(1): 476-526.

5-Typpo KV, Wong HR, Finley SD. Monitoring severity of multiple organ dysfunction syndrome: new technologies. Pediatric Critical Care Medicine. 2017; 3(1): 24-31.

6-Annane D, Trabold F, Sharshar T, et al. Inappropriate sympathetic activation at onset of septic shock. American Journal of Respiratory and Critical Care Medicine. 2000; 160(1): 458-465.

7-Bradkley B, Green GC, Batkin I, Seely AJ. Feasibility of continuous multiorgan variability analysis in the intensive care unit. Journal of Critical Care. 2012; 27(1): 9-20.

8-Seely AJ, Bravi A, Herry C, et al. Do heart and respiratory rate variability improve prediction of extubation outcomes in critically ill patients? Journal of Critical Care. 2014; 18(1): 65.

9-Andrades ME, Morina A, Spasic S, Spasojevic I. Bench-to-bedside review: sepsis-from the redox point of view. Journal of Critical Care. 2011; 15(1): 230.

10-Fisher BJ, Seropian IM, Kraskausakas D, et al. Ascorbic acid attenuates lipopolysaccharides- induced acute lung injury. Critical Care Medicine. 2011; 39(1): 1454-1460.