Causes Of Multiple Organ Dysfunction Syndrome Research Articles

Complement Activation in Patients With Heat-Related Illnesses: Soluble CD59 Is a Novel Biomarker Indicating Severity of Heat-Related Illnesses.

OBJECTIVES:Although multiple organ dysfunction syndrome (MODS) is the main cause of death in patients with heat-related illnesses, its underlying pathophysiological mechanism remains elusive. Complement activation is considered one of the main causes of MODS in patients with sepsis and trauma. Considering the pathophysiological similarity of heat related-illnesses with sepsis and trauma, the complement system might be activated in patients with heat-related illnesses as well. Our aim was to investigate whether excessive complement activation occurs in patients with heat-related illnesses.DESIGN:Prospective observational study.SETTING:Emergency department in the university hospital.PATIENTS:Thirty-two patients with heat-related illnesses and 15 age-matched healthy controls were enrolled in this study.INTERVENTIONS:Blood samples were collected from the study subjects for the measurement of complement factors.MEASUREMENTS AND MAIN RESULTS:Complement component 3a (C3a), complement component 5a (C5a), C5b-9, complement factor B (Ba), Factor H, and soluble CD59 in plasma were measured. The levels of C3a, C5a, C5b-9, and Ba significantly increased in patients with heat-related illnesses on day 0 compared with those in the healthy controls. Soluble CD59 was significantly high in patients with heat-related illnesses on day 0 and showed a correlation with the severity of the condition (Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and staging scores), Japanese Association for Acute Medicine disseminated intravascular coagulation scores, and the coagulation system (prothrombin time and fibrin degradation products).CONCLUSIONS:The complement system was activated in patients with heat-related illnesses, suggesting that it is one of the causes of MODS. Soluble CD59 may be a potent biomarker for the severity of heat-related illnesses.

English

BACKGROUND To study the clinical profile and outcome of multiple organ dysfunction syndrome (MODS) in previously healthy adult patients and to assess the correlation between sequential organ failure assessment (SOFA) score at admission and mortality in these patients. METHODS This study was conducted at a tertiary care hospital attached to a medical college of south India. This was a prospective observational study. All adult patients presenting with multiple organ dysfunction syndrome between October 2010 and June 2012 were selected for the study. SOFA score was recorded for all the patients at the time of admission. Patients were followed up till the time of death or discharge. RESULTS In this study, majority of the cases were males and belonged to middle age group. Epidemic diseases such as scrub typhus and leptospirosis were the most common causes of MODS. Fever was the most common presenting symptom of MODS. Majority of patients recovered. Higher SOFA score at admission is associated with increased mortality, duration of hospital stay, requirement of ventilatory support, haemodialysis, and central venous access. CONCLUSIONS Infectious diseases are responsible for most cases of MODS. Higher SOFA score at admission is associated with increased morbidity and mortality. Majority of people recover with appropriate treatment. KEYWORDS MODS, Clinical Profile, SOFA Score, Outcome

Gut-origin sepsis in the critically ill patient: pathophysiology and treatment.

Gut permeability is increased in critically ill patients, and associated with the development of the systemic inflammatory response syndrome and multiple organ dysfunction syndrome (MODS). The pathogenetic link(s) and potential therapies are an area of intense research over the last decades. We thoroughly reviewed the literature on gut-origin sepsis and MODS in critically ill patients, with emphasis on the implicated pathophysiological mechanisms and therapeutic interventions. Intestinal barrier failure leading to systemic bacterial translocation associated with MODS was the predominant pathophysiological theory for several years. However, clinical studies with critically ill patients failed to provide the evidence of systemic spread of gut-derived bacteria and/or their products as a cause of MODS. Newer experimental data highlight the role of the mesenteric lymph as a carrier of gut-derived danger-associated molecular patterns (DAMPs) to the lung and the systemic circulation. These substances are recognized by pattern recognition receptor-bearing cells in diverse tissues and promote proinflammatory pathways and the development MODS. Therefore, the gut becomes a pivotal proinflammatory organ, driving the systemic inflammatory response through DAMPs release in mesenteric lymph, without the need for systemic bacterial translocation. There is an emerging need for application of sensitive non-invasive and easily measured biomarkers of early intestinal injury (e.g., citrulline, intestinal fatty acid protein, and zonulin) in our everyday clinical practice, guiding the early pharmacological intervention in critically ill patients to restore or prevent intestinal injury and improve their outcomes.

English

Multiple organ dysfunction syndrome (MODS) is a systemic, dysfunctional inflammatory response that requires longer admissions in acute medical care unit with high mortality rate. The present study was done prospectively to evaluate clinical profile and etiological spectrum of patients admitted in acute medical care unit categorized under multi- organ dysfunction syndrome (MODS) and to correlate outcome of MODS. 50 patients of ≥ 18 years age who were admitted in Acute Medical Care Unit, Department of Medicine, Government General Hospital, Kakinada, with more than one organ dysfunction, requiring intervention were studied during 2010-2012. In all cases provisional diagnosis was made by taking detailed history and clinical examination, and were subjected to the relevant investigations. The criteria were used to include under MODS were assessed on respiratory, renal gastrointestinal, central nervous system, Glasgow coma scale cardiovascular, hematological parameters. The outcome of MODS was correlated by application of APACHE-II score on admission day, serial SOFA score on day 1 and 3, serial serum albumin measurement on day 1 and 5. There was multiorgan involvement .Most common organ failed was renal 30 (60%), followed by CNS 27 (54%), respiratory 25 (50%), CVS 23 (46%), GIT 17 (34%), hematologic 9 (18%). Sepsis was the most common cause of MODS in 24 (48%) patients. Most common organ dysfunction as a predictor of mortality was CNS in 17 (77%) out of 22 patients expired, followed by Respiratory in 13 (59%), Renal 11 (50%), CVS 10 (45%), GIT 9 (40%), Hematologic 2 (9%). Maximum incidence of mortality was seen when ≥5 organs failed. There was significant correlation statistically in our study between APACHE II score on admission and outcome as Pearson chi-square “p”< 0.001Mean SOFA score of survivors on day 1 was 6±2 and on day 3 was 2±1. Mortality significantly decreased (3.44%) on day 3 if SOFA score was ≤7. Multi-Organ Dysfunction Syndrome (MODS) was common in younger age group with the mean age of40 years. Sepsis (48%) was the most common cause of MODS, followed by other causes. Maximum incidence of mortality (55%) was seen if the first failed organ was respiratory system and when ≥5 organs failed. Highest incidence of mortality was seen in 8 th decade (100%). APACHE II score on admission, serial SOFA scores, and serial albumin measurements can help ICU physicians in admitting patients, monitoring the clinical course, assessment of organ dysfunction, predicting mortality and for transferring patients out from ICU and thus in proper utilization of ICU resources.

Causes of Multiple Organ Dysfunction During Cardiosurgical Operations under Extracorporeal Circulation

Objective: to reveal possible causes of postoperative multiple organ dysfunction syndrome (MODS) in patients after surgery under extracorporeal circulation (EC), by measuring the level and balance of pro- and anti-inflammatory cytokines. Subjects and methods. The investigation enrolled 162 patients who had undergone operations on the heart and thoracic aorta. The levels of interleukins (IL)-6, IL-8, and IL-10 were determined by ELISA. Results. At surgery under EC, MODS was encountered in 5.7%, mortality was 55.6%. The principal causes of MODS were prolonged EC concurrent with bleeding (23%), massive hemorrhage (16%), perioperative myocardial infarction and cardiogenic shock (15%), prolonged EC (12%), acute lung injury (12%), disseminated intravascular coagulation (10%), allergic and anaphylactic reactions (9%), and intravascular hemolysis (6%). The levels of pro- and anti-inflammatory cytokines were substantially increased in all the patients after surgery under EC irrespective of the presence of MODS in the postoperative period. The patients with MODS displayed pro- and anti-inflammatory cytokine imbalance due to a preponderance of the proinflammatory activity of a systemic response. During massive hemorrhage (more than 20 ml/kg), the patients with MODS exhibited a reduction in the two pools of cytokines. In the absence of MODS, there was a parallel increase in both pro- and anti-inflammatory cytokines. The magnitude of a change in the level of cytokines is related to the volume of blood loss. During prolonged EC (more than 170 min), the patients with MODS had a higher pro- and anti-inflammatory cytokine ratio due to the elevated levels of both pools, but the elevation of anti-inflammatory cytokines was more pronounced. In the patients without MODS, the values of both groups of interleukins were sigmficantly unchanged with longer duration of EC. Key words: multiple organ dysfunction syndrome, systemic inflammatory reaction, interleukins 6, 8, 10, extracorporeal circulation, operations on the heart and thoracic aorta.

Sepsis induces platelet mitochondrial uncoupling and a gradual increase in respiratory capacity that is negatively associated with clinical outcome

Mitochondrial dysfunction has been suggested as a contributing factor in the pathogenesis of multiple organ dysfunction syndrome (MODS) and sepsis is the leading cause of MODS. Also, restoration of mitochondrial function, known as mitochondrial biogenesis, has been implicated as a key factor for the recovery of organ function in patients with sepsis. Here we investigated platelet mitochondrial respiratory function in patients with sepsis during the first week after disease onset.

A clinical study on the diagnostic criteria of multiple organ dysfunction syndrome

To develop diagnostic criteria of multiple organ dysfunction syndrome (MODS) by a prospective and multi-center clinical investigation. The data of 1087 MODS cases obtained from ICU of 37 hospitals from March 2002 to January 2005 in 11 provinces in China were analyzed in order to derive the diagnostic criteria of MODS. This MODS diagnostic criteria involved 7 organs. To diagnose MODS, the original cause of MODS should be identified, then there should be two or more organs showing signs of dysfunction. The criteria for organ dysfunction were as follows. (1) Cardiovascular system: SBP < 90 mm Hg (1 mm Hg = 0.133 kPa), MAP < 70 mm Hg, signs of shock, ventricular tachycardia, ventricular fibrillation, or myocardial infarction; (2) Respiratory system: oxygenation index < 300 mm Hg; (3) Nervous system: indifference, restlessness, lethargy, light coma, or deep coma, Glasgow score < or = 14; (4) Blood system: PLT < 100 x 10(9)/L; CT, APTT, and PT prolonged or shortened; positive plasma protamine paracoagulation; (5) Liver: TBIL > 20. 5 micromol/L, ALB < 28 g/L; (6) Kidney: Cr > 123.8 micromol/L, urinary volume < 500 ml/24 h; (7) Gastro-intestine: bowel sounds decreased or disappeared; retention in the stomach, or positive occult blood feces with dark stools or haematemesis; intraabdominal pressure (intravesical pressure) > or = 11 cm H2O (1 cm H2O = 0.098 kPa). Any organ function met with one of the above conditions was considered to have dysfunction. This diagnostic criterion of multiple organ dysfunction syndrome has been developed by this research, but it needs to accumulate experience by clinical practice and to revise the diagnosis criteria.

Multiple organ dysfunction in ulcerative colitis.

The mortality rate in severe ulcerative colitis (UC) is commonly attributed to major colonic complications or surgical procedures. Early recognition of the severity of the colitis, intensive medical treatment, and prompt surgery have all contributed to improving its outcome over the past 40 yr. Recently, we have observed some fatal cases of severe UC in which death was related to multiple organ dysfunction syndrome (MODS). This complication, associated with a very high mortality rate, may occur in several acute critical diseases, both infectious and noninfectious, but has so far not been reported in UC. The aim of this study was to evaluate the prevalence and outcome of MODS in severe UC. The records of 180 consecutive patients admitted to the Gastrointestinal Unit, University of Rome for an acute severe attack of UC during the period 1976-1998 were retrospectively analyzed. Severity of UC was defined according to the criteria of Truelove and Witts. MODS was defined according to the original criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference 1992. All patients were on a standard intensive regimen consisting of total parenteral nutrition and hydrocortisone 100 mg q.i.d. Colectomy was performed according to the timing of the Oxford intensive regimen. Of these 180 severe UC patients, 11 (6.1%) experienced clinical and laboratory features of MODS. The lung was involved in five patients, the kidney in three, the liver in seven, the central nervous system in three, the hematological system in three, and the pancreas in one. MODS was preceded by toxic megacolon in five patients and by so-called "impending megacolon" in four, whereas in two patients no previous complications of UC were observed. MODS developed during the first attack of colitis in seven patients and during relapse in four. The overall mortality rate was 12/180 (6.6%). Of the 12 patients who died, eight (72.7%) had MODS. These data indicate that UC must be included among the causes of MODS. In our referral center for inflammatory bowel diseases, MODS was responsible for the majority of UC cases with a fatal outcome. The timely identification of signs of MODS should prompt admission to an intensive care unit and emergency surgery.

Multiple organ dysfunction in ulcerative colitis

OBJECTIVE: The mortality rate in severe ulcerative colitis (UC) is commonly attributed to major colonic complications or surgical procedures. Early recognition of the severity of the colitis, intensive medical treatment, and prompt surgery have all contributed to improving its outcome over the past 40 yr. Recently, we have observed some fatal cases of severe UC in which death was related to multiple organ dysfunction syndrome (MODS). This complication, associated with a very high mortality rate, may occur in several acute critical diseases, both infectious and noninfectious, but has so far not been reported in UC. The aim of this study was to evaluate the prevalence and outcome of MODS in severe UC. METHODS: The records of 180 consecutive patients admitted to the Gastrointestinal Unit, University of Rome for an acute severe attack of UC during the period 1976–1998 were retrospectively analyzed. Severity of UC was defined according to the criteria of Truelove and Witts. MODS was defined according to the original critiera of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference 1992. All patients were on a standard intensive regimen consisting of total parenteral nutrition and hydrocortisone 100 mg q.i.d. Colectomy was performed according to the timing of the Oxford intensive regimen. RESULTS: Of these 180 severe UC patients, 11 (6.1%) experienced clinical and laboratory features of MODS. The lung was involved in five patients, the kidney in three, the liver in seven, the central nervous system in three, the hematological system in three, and the pancreas in one. MODS was preceded by toxic megacolon in five patients and by so-called “impending megacolon” in four, whereas in two patients no previous complications of UC were observed. MODS developed during the first attack of colitis in seven patients and during relapse in four. The overall mortality rate was 12/180 (6.6%). Of the 12 patients who died, eight (72.7%) had MODS. CONCLUSIONS: These data indicate that UC must be included among the causes of MODS. In our referral center for inflammatory bowel diseases, MODS was responsible for the majority of UC cases with a fatal outcome. The timely identification of signs of MODS should prompt admission to an intensive care unit and emergency surgery.