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Holzheimer RG, Mannick JA, editors. Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt; 2001.
The most common cause of death for patients admitted to a contemporary intensive care unit (ICU) is a clinical condition that owes its existence to the development of the ICU. Variously known as the multiple organ dysfunction syndrome (MODS), multi-organ failure, multiple systems organ failure, or through some of its more prominent manifestations, as the acute respiratory distress syndrome (ARDS) or disseminated intravascular coagulation (DIC), MODS is as poorly understood as it is prevalent. Even its terminology merits comment. Although originally described as multiple organ failure, it is evident that normal physiologic function of the failing organ systems can be restored in survivors. Thus characterization of the process as multiple organ dysfunction is more appropriate. And although the syndrome involves the dysfunction of many organs, it also affects physiologic systems not classically thought of as organs, including the hematologic system, immune system, or the endocrine system. Finally, although it is described as a syndrome, its clinical course and causes are highly variable, and there is only the most general form of consensus regarding the organs whose dysfunction comprises the syndrome, or the criteria that should be used to describe this dysfunction.
The Multiple Organ Dysfunction Syndrome (MODS) can be defined as the development of potentially reversible physiologic derangement involving two or more organ systems not involved in the disorder that resulted in ICU admission, and arising in the wake of a potentially life-threatening physiologic insult.
Organ system specific support is the raison d'être for the ICU, and it is not surprising, therefore, that the need for such support has become a model for describing the clinical course of the critically ill patient. The observation that critically ill patients die, not as a result of the progression of the disorder that precipitated ICU admission, but of a complex series of physiologic derangements that develop following resuscitation and management in the ICU was first made in the 1960's. Baue, in 1975, published a landmark editorial in which he commented on the striking similarity of the post mortem findings in patients dying in an ICU and suggested that it was not the failure of a single system, but the concomitant failure of multiple interdependent organ systems that was the unsolved problem in critical care. Subsequent reports highlighted the important role of occult, uncontrolled infection in the pathogenesis of MODS, although control of infection did not necessarily result in reversal of the physiologic derangements, nor was infection universally present in patients with the syndrome.
MODS: Clinical and pathologic description
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. The first descriptions of the syndrome generally counted the number of failing systems, using as descriptors, the need for clinical intervention. More recently several similar descriptive scales have been developed, based on the quantification of organ dysfunction as a numeric scale. Each uses the same six organ systems to characterize MODS - the respiratory, cardiovascular, renal, hepatic, neurologic, and hematologic systems. They differ in minor ways with respect to the selected parameters to describe cardiovascular dysfunction, and in the timing and weighting of the variables selected. The Multiple Organ Dysfunction (MOD) score, a scale that uses physiologic variables exclusively is presented in table I.
Table I
The multiple organ dysfunction (MOD) score.
Regardless of how MODS is characterized, it is apparent that the risk of ICU death increases as the severity of organ dysfunction - whether the number of failing organs (table II), or the overall degree of dysfunction (fig. 1) increases.
Table II
Prognosis in multiple organ failure.
The histologic features of the organs involved in MODS are less well characterized, but generally include evidence of edema, inflammation, tissue ischemia or necrosis, and variable degrees of fibrosis and repair. These alterations, in turn, are responsible for the clinical features of MODS in each of its component systems.
Lung
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.
Kidney
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.
Heart and cardiovascular system
The acute cardiovascular derangements of MODS consist of five features:
- 1.
a generalized reduction in peripheral vascular tone, mediated largely through the local vasodilatory activity of nitric oxide
- 2.
a generalized increase in capillary permeability producing diffuse capillary leak and edema, and contributing to further dysfunction in other organ systems
- 3.
alterations in regional blood flow to specific organ beds
- 4.
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
- 5.
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. Since their net physiologic consequence is hypotension that is refractory to increased preload, we have used a measure called the pressure-adjusted heart rate (PAR) to quantify cardiovascular dysfunction in the MOD score. Calculated as the product of the heart rate and the ratio of central venous to mean arterial pressure (HR × CVP/MAP), it is, like the PO2/FIO2 ratio, a reflection of physiology, corrected for therapy; increasing values reflect worsening cardiovascular dysfunction.
Gastrointestinal/hepatic
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.
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.
Neurologic
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.
Hematologic
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). Like other manifestations of MODS, the causes of thrombocytopenia in critical illness are many - heparin-induced thrombocytopenia, intravascular consumption, and reduced production to name a few.
Immunologic
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 avirulent organisms. The characteristic flora of ICU-acquired infection in MODS includes coagulase-negative Staphylococci, Enterococci, Candida, and Pseudomonas.
Endocrine/metabolic
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.
Prevention of MODS
MODS is less a syndrome to be treated than a complication to be prevented. Iatrogenic factors, or processes amenable to prophylactic intervention figure prominently in the expression of the syndrome.
Because the syndrome almost invariably arises following the activation of a host inflammatory response, MODS can be considered to be the maladaptive consequence of acute inflammation, the systemic equivalent of functio laesa, or loss of function, a cardinal sign of acute localized inflammation. To date, however, interventions targeted at the host inflammatory response have not proven effective in preventing MODS or minimizing its evolution. Other simpler approaches are more promising. Table III summarizes ICU interventions for which there is evidence of significant benefit, reflected in reduced organ dysfunction, or improved ICU survival. The list is a sampling that is of necessity inadequate. Any intervention that can prevent death or bring physiologic benefit to critically ill patients might reasonably be included; on the other hand, rigorous evaluation of most commonly accepted ICU interventions has not been undertaken.
Table III
The prevention of MODS in critical illness.
Conclusion
The multiple organ dysfunction syndrome is both a syndrome and a form of clinical shorthand for the approach to patient care that is exemplified by contemporary ICU practice. As a syndrome, it is intimately linked to the adaptive host response to injury or infection, and it is to be expected that interventions that can modulate the expression of this response will ultimately prove effective in improving clinical outcome. As a clinical shorthand, it categorizes the range of interventions available to support critically ill patients, and underlines the prime importance of recognizing the potential for iatrogenic harm implicit in the increasingly complex and technological repertoire we use to care for them.
References
- 1.
- Deitch E A. Multiple organ failure. Pathophysiology and potential future therapy. Ann Surg. (1992);216:117–134. [PMC free article: PMC1242583] [PubMed: 1503516]
- 2.
- Beal A L, Cerra F B. Multiple organ failure syndrome in the 1990's. Systemic inflammatory response and organ dysfunction. JAMA. (1994);271:226–233. [PubMed: 8080494]
- 3.
- Vincent J L. Prevention and therapy of multiple organ failure. World J Surg. (1996);20:465–470. [PubMed: 8662136]
- 4.
- Tran D D, Cuesta M A, Van Leeuwen P A M, Nauta J J P, Wesdorp R I C. Risk factors for multiple organ system failure and death in critically injured patients. Surgery. (1993);114:21–30. [PubMed: 8102816]
- 5.
- Sauaia A, Moore F A, Moore E E, Haenel J B, Read R A, Lezotte D C. Early predictors of postinjury multiple organ failure. Arch Surg. (1994);129:39–45. [PubMed: 8279939]
- 6.
- Marshall J C, Cook D J, Christou N V, Bernard G R, Sprung C L, Sibbald W J. Multiple organ dysfunction score: A reliable descriptor of a complex clinical outcome. Crit Care Med. (1995);23:1638–1652. [PubMed: 7587228]
- 7.
- Vincent J L, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart K, Suter P, Thijs L G. The sepsis-related organ failure assessment (SOFA) score to describe organ dysfunction/failure. Intens Care Med. (1996);22:707–710. [PubMed: 8844239]
- 8.
- Garber B G, Hébert P C, Yelle J D, Hodder R V, McGowan J. Adult respiratory distress syndrome: A systematic overview of incidence and risk factors. Crit Care Med. (1996);24:687–695. [PubMed: 8612424]
- 9.
- Petty T L. Acute respiratory distress syndrome: Consensus, definitions, and future directions. Crit Care Med. (1996);24:555–556. [PubMed: 8612402]
- 10.
- Brivet F G, Kleinknecht D J, Loirat P, Landais P J M, Bedock B, Bleichner G, Richard C, Coste F, Brun-Buisson C, Sicot C, Tenaillon A, Gajdos P, Blin F, Saulnier F, Agostini M M, Nicolas F, Fery-Lemonnier E, Staikowski F, Carlet J, Guivarch G, Fraisse F, Ricome J, Tempe J D, Mezzarobba P. Acute renal failure in intensive care units - Causes, outcome, and prognostic factors of hospital mortality: A prospective, multicenter study. Crit Care Med. (1996);24:192–198. [PubMed: 8605788]
- 11.
- Hebert P C, Wells G, Blajchman M A, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. the Transfusion Requirements in Critical Care Investigators for the Canadian Critical Care Trials Group. A multicentre randomized controlled clinical trial of transfusion requirements in critical care. N Engl J Med. (1999);340:409–417. [PubMed: 9971864]
- 12.
- Heyland D K, Cook D J, King D, Kernerman P, Brun-Buisson C. Maximizing oxygen delivery in critically ill patients: A methodologic appraisal of the evidence. Crit Care Med. (1996);24:517–524. [PubMed: 8625644]
- 13.
- D'Amico, Pifferi S, Leonetti C, Torri V, Tinazzi A, Liberati A. on behalf of the study investigators. Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomized controlled trials. BMJ. (1998);316:1275–1285. [PMC free article: PMC28528] [PubMed: 9554897]
- 14.
- Nathens A B, Marshall J C. Selective decontamination of the digestive tract (SDD) in surgical patients. Arch Surg. (1999);134:170–176. [PubMed: 10025458]
- 15.
- Stewart T E, Meade M O, Cook D J, Granton J T, Hooder R V, Lapinsky S E, Mazer C D, McLean R F, Rogovein T S, Schouten B D, Todd T R J, Slutsky A S. The Pressure- and Volume-Limited Ventilation Strategy Group. Evalution of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. N Engl J Med. (1998);338:355–361. [PubMed: 9449728]
- 16.
- Cook D J, Guyatt G H, Marshall J C, Leasa D, Fuller H D, Hall R, Peters S, Rutledge F, MacLellan A P, Wood G, Kirby A, Tweeddale M, Pagliarello J, Johnson R, Griffith L E. The Canadian Critical Care Trials Group. A randomized trial of sucralfate versus ranitidine for stress ulcer prophylaxis in critically ill patients. N Engl J Med. (1998);338:791–797. [PubMed: 9504939]
- 17.
- Bengmark S, Gianotti L. Nutritional support to prevent and treat multiple organ failure. World J Surg. (1996);20:474–481. [PMC free article: PMC7101626] [PubMed: 8662138]
- The multiple organ dysfunction syndrome - Surgical TreatmentThe multiple organ dysfunction syndrome - Surgical Treatment
- yvcB [Bacillus subtilis subsp. subtilis str. 168]yvcB [Bacillus subtilis subsp. subtilis str. 168]Gene ID:936563Gene
- DEFB134 defensin beta 134 [Homo sapiens]DEFB134 defensin beta 134 [Homo sapiens]Gene ID:613211Gene
- Golga3 golgin A3 [Mus musculus]Golga3 golgin A3 [Mus musculus]Gene ID:269682Gene
- OSTCP1 oligosaccharyltransferase complex subunit pseudogene 1 [Homo sapiens]OSTCP1 oligosaccharyltransferase complex subunit pseudogene 1 [Homo sapiens]Gene ID:202459Gene
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