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The compensatory anti-inflammatory cytokine interleukin 10 response in pediatric sepsis-induced multiple organ failure.

STUDY OBJECTIVES: To determine the circulating anti-inflammatory cytokine interleukin 10 (IL-10) response during the development of sepsis-induced multiple organ failure in children. DESIGN: Prospective study. SETTING: University pediatric ICU. PATIENTS: Fifty-three consecutive children with sepsis and 15 critically ill children without sepsis. INTERVENTIONS: Plasma IL-10, interleukin 6 (IL-6), and nitrite+nitrate (stable end products of nitric oxide) levels and an organ failure index (OFI indicating the number of failing organ systems) were determined in 53 children on days 1 to 3 of sepsis and in control children on day 1. The effect of exogenous human IL-10 or neutralizing IL-10 antibody on supernatant IL-6 levels in ex vivo whole blood culture from 17 children on day 1 of sepsis. MEASUREMENTS AND RESULTS: Children with three or more organ failures had higher plasma IL-10 levels than children with less than 3 organ failures (days 1 and 3; p<0.05). Children who developed sequential pulmonary/hepatic/renal failure had higher IL-10 levels (days 1 to 3; p<0.05). Nonsurvivors had higher IL-10 levels (day 3; p<0.05). IL-10 levels correlated with IL-6 levels (days 1 and 2) and nitrite+nitrate levels (days 1 and 3; p<0.05). Whole blood samples incubated ex vivo with exogenous recombinant human IL-10 had decreased supernatant IL-6 levels (p<0.05) and neutralizing IL-10 antibody showed no significant effect. CONCLUSION: A persistent compensatory anti-inflammatory cytokine response characterizes sepsis-induced multiple organ failure. Administration of exogenous IL-10 may inhibit the early proinflammatory response; however, identification of individual immune responsiveness and possibility of persistent infection could be important to rational use in the later stages of pediatric sepsis.

Adolescent↗

[Observed vs expected mortality in the emergency service of a general hospital. Evaluation by the APACHE II and multiple organ failure classification systems].

UNLABELLED: Problem that originated the investigation: It was not known if the observed mortality in the Emergency room of the Tijuana General Hospital was lower, equal or higher, than the expected mortality. OBJECTIVES: 1) Evaluate in a prospective fashion the mortality rate in that hospital service, and then compare that rate with an expected mortality rate proposed in the literature (Role). 2) Determine the prognostic value in our hospital of the Multiple Organ Failure classification system (MOF). The Multiple Organ Failure classification system showed in our study an excellent predicting capacity for mortality.

APACHE↗

Adult respiratory distress syndrome. Sequence and importance of development of multiple organ failure. The Prostaglandin E1 Study Group.

STUDY OBJECTIVE: To determine the epidemiology of multiple organ failure (MOF) in patients with the adult respiratory distress syndrome. PATIENTS: We followed up 50 patients with serial determinations of respiratory and nonrespiratory organ function for seven days after diagnosis. DESIGN: Data were stratified between patients who died and those who survived (defined as hospital discharge). MEASUREMENTS AND RESULTS: Values that did not differ at any time between the two groups of patients included oxygen availability, oxygen consumption, oxygen extraction, PaCO2, respiratory rate, heart rate, systolic blood pressure, cardiac output, stroke index, systemic vascular resistance, and temperature. Patients who died had greater defects in oxygenation (from day 1 through day 7). They also exhibited decreased arterial oxygen content (from day 1 to day 4), decreased mixed venous oxygen content (day 1), increased peak inspiratory pressure (present on day 2, persisted to day 5, reappeared on day 7), decreased diastolic blood pressure (seen on days 1 through 3, reappeared on day 7), and increased mean pulmonary artery pressure (seen on days 2 and 3). Nonsurvivors also exhibited greater degrees of thrombocytopenia (from day 1 to day 4). Decreases in pH (seen on day 1, reappeared from days 4 to 7), abnormalities in liver function (seen only on day 1), and increases in serum creatinine levels (appeared on day 7) were also observed. CONCLUSIONS: Multiorgan dysfunction (MOD) was frequently observed in both groups of patients. Alterations in organ function and the pattern of abnormalities were often subtle and would not be characterized as significant organ dysfunction by most available organ scoring systems. Adult respiratory distress syndrome is a manifestation of systemic disease produced by widespread increases in endothelial permeability; lung dysfunction dominates the early clinical course. When respiratory function is supported, it becomes evident that alterations occur in other organs. Multiorgan failure is really a misnomer; the term emphasizes end-stage changes. Multiorgan dysfunction is common and often resolves without progressing to MOF. Alternatively, MOD can progress to MOF.

Blood Pressure↗

[Fulminant autoimmune hemolytic anemia with multiple organ failure].

We report a rare case of fulminant autoimmune hemolytic anemia (AIHA) with multiple organ failure (MOF). A 40-year-old man was emergently admitted to our hospital because of conscious disturbance and jaundice. The peripheral blood revealed RBC 68 x 10(4)/microliter, Hb 3.5 g/dl, Ht 8.9%, Ret 30% (20,400/microliter), WBC 20,300/microliter, Plts 16.9 x 10(4)/microliter, indirect bilirubin 9.4 mg/dl. Both direct and indirect Coombs test were positive and the IgG autoantibody was identified. Bone marrow aspiration revealed hypercellularity with increased megakaryocytes and erythroid hyperplasia. The patient was diagnosed as having idiopathic warm type of AIHA and the therapy was started with prednisolone 80 mg/day from the first day of admission but hemolysis with reticulocytopenia was so rapidly progressive that he was in acutely life-threatening state and MOF (acute renal failure, adult respiratory distress syndrome, congestive heart failure, liver dysfunction, rhabdomyolysis) appeared on the third hospital day. Plasma exchange therapy and hemodialysis were started and high dose methylprednisolone was given soon after rapid administration of sufficient blood transfusion. Dramatic improvement of hemolysis was noted and MOF was controlled after starting these therapies, but he died of exacerbation of MOF probably due to sepsis 40 days later.

Adult↗

Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease.

We studied prospectively the quantitative relation of circulating endotoxin (lipooligosaccharides [LOSs]) and the development of multiple organ failure and death in 45 consecutively admitted patients with bacteriologically verified systemic meningococcal disease (SMD). A plasma LOS level of greater than 700 ng/L correlated with development of severe septic shock (P less than .0001), adult respiratory distress syndrome (P = .0035), a pathologically elevated serum creatinine level (P less than .0001), or death as a consequence of multiple organ failure (P = .0002). Initial plasma LOS levels of less than 25, 25-700, 700-10,000, and greater than 10,000 ng/L were associated with 0%, 14%, 27%, and 86% fatality, respectively. The LOS half-life after initiation of antibiotic therapy was 1-3 h. Increasing plasma LOS levels were never seen. These observations suggest that LOS quantitation using the limulus amebocyte lysate assay with a chromogenic substrate gives important progsnotic information and may provide new insight concerning pathophysiological aspects of SMD.

Adolescent↗

Abdominal compartment syndrome: the cause or effect of postinjury multiple organ failure.

Abdominal compartment syndrome (ACS) has emerged to be a significant problem in patients who develop postinjury multiple organ failure (MOF). Current laboratory research suggests that ACS could be a second hit for the development of MOF. Recent studies demonstrate that ACS is an independent predictor of MOF and that the prevention of ACS decreases the incidence of MOF. The Trauma Research Centers at the University of Colorado and the University of Texas-Houston Medical School are focused on defining the role of the gut in postinjury MOF. Because ACS is a plausible modifiable risk factor, our interest has been to 1) describe the epidemiology of ACS, 2) build prediction models, 3) provide strategies for prevention and treatment of ACS, and 4) develop relevant laboratory models. This review summarizes our findings.

Abdomen↗

Bench-to-bedside review: thrombocytopenia-associated multiple organ failure--a newly appreciated syndrome in the critically ill.

New onset thrombocytopenia and multiple organ failure (TAMOF) presages poor outcome in critical illness. Patients who resolve thrombocytopenia by day 14 are more likely to survive than those who do not. Patients with TAMOF have a spectrum of microangiopathic disorders that includes thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC) and secondary thrombotic microanigiopathy (TMA). Activated protein C is effective in resolving fibrin-mediated thrombosis (DIC); however, daily plasma exchange is the therapy of choice for removing ADAMTS 13 inhibitors and replenishing ADAMTS 13 activity which in turn resolves platelet: von Willebrand Factor mediated thrombosis (TTP/secondary TMA).

Critical Illness↗

Early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure.

Polymorphonuclear neutrophils (PMNs) play a pivotal role in the inflammation that precedes multiple organ failure (MOF). In a rat model of MOF, PMNs become primed for enhanced superoxide anion (O2-) release and CD11b expression, sequester in end organs, and produce organ failure. Therefore, we hypothesized that circulating PMNs harvested in the first 24 hours after injury from trauma patients at risk for MOF would (1) exhibit a primed O2- release, (2) upregulate CD11b expression, and (3) show evidence of sequestration in tissues. Extracellular PMN O2- release and CD11b receptor expression were measured at 3, 6, 12, and 24 hours after injury in 33 torso trauma patients with Injury Severity Scores > 15; eight patients (24%) developed MOF. Healthy adults served as controls. PMNs after injury were primed for enhanced in vitro O2- release at 3, 6, 12, and 24 hours after injury, indicating prior in vivo priming. CD11b expression was also increased at 6, 12, and 24 hours after injury. Circulating PMN numbers increased sharply at 3 hours after injury, before decreasing dramatically at 6 and 12 hours, suggesting end organ sequestration. At 12 hours after injury, declines in circulating PMNs were significantly greater in MOF than in non-MOF patients (p < 0.05). These data indicate that PMNs are quickly mobilized into the circulation after injury and then primed for enhanced O2- release and CD11b expression. PMN priming appears to be a necessary preamble to PMN sequestration in patients with major torso trauma. Upregulation of PMN function, accompanied by subsequent end organ sequestration, may represent an important early event in the pathogenesis of MOF after injury.

Adult↗

[Use of continuous veno-venous high volume hemofiltration (CVVHVH) in patients with multiple organ failure. Principle and applications].

Between 1987 and 1994 in 24 patients suffering from multiple organ failure the new method of continuous high-volume veno-venous hemofiltration (HVCVVH) was performed. Compared with the usual methods of dialysis and hemofiltration the HVCVVH has proven two advantages: at first, it was possible to obtain a high blood flow through the filter powered by a pump. Secondly the fluid withdrawal from the infracardiac body region and the controlled infusion of fluid into the supracardiac veins was possible without decreasing the cardiac preload in patients with severe disorders of volume distribution. 18 of 24 treated patients had a stable circulation without need of catecholamines after the filtration. In 14 of the 24 patients the FiO2 was reduced to 0.3 and decreased during filtration. 13 patients survived the observation time of 30 days, 2 patients died during the procedure of filtration.

Adult↗

Decreased mesenteric blood flow in experimental multiple organ failure.

Disorders of mucosal blood flow may contribute to gut barrier dysfunction in multiple organ failure (MOF). We evaluated alterations of mesenteric microcirculation in a rat model of MOF. Male Wistar rats received 1 mg/g body weight of zymosan A in 4 ml of mineral oil by intraperitoneal injection and were studied on Days 1, 3, and 5 following injection. A control group received no zymosan. The experimental group also received a fluid resuscitation regimen of 0.9 N saline subcutaneously equal to 0.1 ml/g body weight on the day of zymosan injection and 0.05 ml/g body weight daily thereafter. Day 1 animals tended toward a statistically significantly lower mean arterial pressure versus controls (86.6 +/- 8 mm Hg versus 106 +/- 5 mm Hg, F = 0.09 by ANOVA). Significant arteriolar vasoconstriction occurred on Days 1 and 3 versus control (70 +/- 4 microns and 57 +/- 8 microns versus 96 +/- 3 microns, F = 0.0002). Laser doppler velocity, indicating red blood cell velocity, expressed as a percentage of control paralleled this vasoconstriction (70 +/- 9 and 72 +/- 7%, respectively). We conclude that mesenteric arteriolar vasoconstriction occurs accompanied by decreased red blood velocity. We believe that this is indicative of decreased mesenteric perfusion in this zymosan model of MOF and that survival to Day 5 is associated with a reversal of these microcirculatory changes.

Animals↗

Severity of multiple organ failure (MOF) but not of sepsis correlates with irreversible platelet degranulation.

Multiple hemostatic changes occur in sepsis and multiple organ failure (MOF). To evaluate the role of platelets in patients with sepsis and MOF, we examined changes in surface glycoproteins on circulating platelets of 14 patients with suspected sepsis and MOF. The severity of sepsis and MOF was assessed by the Elebute and APACHE II scoring systems, respectively. Using flow cytometric techniques and platelet specific monoclonal antibodies, platelet surface expression of fibrinogen receptor on GPIIb-IIIa, of von Willebrand Factor receptor GPIb, and of granule glycoproteins (thrombospondin (TSP), GMP-140, GP53) was measured. Plasma membrane expression of GPIIb-IIIa and GPIb on circulating platelets was not affected by sepsis of MOF. Septic patients, however, showed a significantly elevated fibrinogen receptor activity (LIBS1 expression) (p < 0.05) that correlated with severity of disease (r = 0.597, p = 0.043). No significant change in surface expression of granule glycoproteins (TSP, GMP-140, GP53) was noted in septic patients. In contrast, degranulation of granule glycoproteins was significantly elevated in MOF (p < 0.05) which well with severity of MOF (GMP-140, r = 0.611, p = 0.013; TSP, r = 0.643, p = 0.026). We speculate that platelets in sepsis circulate in a hyperaggregable but still reversible state that results in increased risk of microthrombotic events. In the course of the disease, irreversible platelet degranulation of adhesion molecules occurs that may play an important role in the development of MOF.

Adolescent↗

Blood transfusion. An independent risk factor for postinjury multiple organ failure.

OBJECTIVE: To determine if blood transfusion is a consistent risk factor for postinjury multiple organ failure (MOF), independent of other shock indexes. DESIGN: A 55-month inception cohort study ending on August 30, 1995. Data characterizing postinjury MOF were prospectively collected. Multiple logistic regression analysis was performed on 5 sets of data. Set 1 included admission data (age, sex, comorbidity, injury mechanism, Glasgow Coma Scale, Injury Severity Score, and systolic blood pressure determined in the emergency department) plus the amount of blood transfused within the first 12 hours. In the subsequent 4 data sets, other indexes of shock (early base deficit, early lactate level, late base deficit, and late lactate level) were sequentially added. Additionally, the same multiple logistic regression analyses were performed with early MOF and late MOF as the outcome variables. SETTING: Denver General Hospital, Denver, Colo, is a regional level I trauma center. PATIENTS: Five hundred thirteen consecutive trauma patients admitted to the trauma intensive care unit with an Injury Severity Score greater than 15 who were older than 16 years and who survived longer than 48 hours. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The relationship of blood transfusions and other shock indexes with the outcome variable, MOF. RESULTS: A dose-response relationship between early blood transfusion and the later development of MOF was identified. Despite the inclusion of other indexes of shock, blood transfusion was identified as an independent risk factor in 13 of the 15 multiple logistic regression models tested; the odds ratios were high, especially in the early MOF models. CONCLUSIONS: Blood transfusion is an early consistent risk factor for postinjury MOF, independent of other indexes of shock.

Adolescent↗

Multiple organ failure (MOF) after intestinal operations--a clinical and statistical study of the past 5 years.

Multiple Organ Failure that occurred in 35 cases out of a total of 1498 cases after intestinal surgery were studied by an analysis of the clinical and statistical data from the past 5 years (1984-1988). 1. The incidence of MOF after intestinal surgery was 2.3%. 2. Twenty-eight of MOF resulted from severe infections. 3. The incidence of infection was highest after esophageal operations. 4. Hepatic failure was the most common type of primary organ failure and renal failure was the second most common. 5. The prognosis for MOF was very poor with a survival rate of 8.7%.

Digestive System Surgical Procedures↗

[Multiple organ failure syndrome in critically ill patients].

A new approach to defining the notion of multiple organ failure is proposed. It is based on division of the organ humoral injuries at the stages of dysfunction, insufficiency, and failure. Criteria of these stages are defined for the central nervous and cardiovascular systems, lungs, liver, kidneys, and gastrointestinal tract.

APACHE↗

Multicenter trial of prolonged infusions of rocuronium bromide in critically ill patients: effects of multiple organ failure.

BACKGROUND: This study was done to determine the safety, efficacy, dosing requirements, and spontaneous recovery profiles of prolonged infusions of rocuronium bromide in the critically ill. METHODS: This multicenter, prospective, nonrandomized, open label trial enrolled 32 patients at two university-based medical centers. Patients who were determined to require neuromuscular blockade for at least 24 hours received a bolus of 0.6 mg/kg of rocuronium. After subsequent recovery of two responses (T2) to the TOF stimulation, an infusion of rocuronium was begun at 10 microg/kg/min and continued for 24 to 120 hours as required by the patients' clinical status. RESULTS: Patients were divided into multiple organ failure (MOF) and non-multiple organ failure (non-MOF) groups on enrollment. The mean infusion rates for the MOF and non-MOF groups were 0.2 and 0.5 mg/kg/hour, respectively. CONCLUSION: The mean infusion rate of rocuronium that provides approximately 90% blockade is less for critically ill patients with MOF. Spontaneous recovery was prolonged in patients with MOF.

Adult↗

Cost-effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis with multiple organ failure.

OBJECTIVES: The aim of this study was to estimate the expected cost and clinical benefits associated with the use of drotrecogin alfa (activated) (Xigris; Eli Lilly and Company; Indianapolis, IN) in the French hospital setting. METHODS: The recombinant human activated PROtein C Worldwide Evaluation in Severe Sepsis (PROWESS) study results (1271 patients with multiple organ failure) were adjusted to 9,948 hospital stays from a database of Parisian area intensive-care units (ICUs)-the CubRea (Intensive Care Database User Group) database. The analysis features a decision tree with a probabilistic sensitivity analysis. RESULTS: The cost per life year gained (LYG) of drotrecogin treatment for severe sepsis with multiple organ failure (European indication) was estimated to be dollars 11,812. At the hospital level, the drug is expected to induce an additional cost of dollars 7545 per treated patient. The incremental cost-effectiveness ratio ranges from dollars 7873 per LYG for patients receiving three organ supports during ICU stay to dollars 17,704 per LYG for patients receiving less than two organ supports. CONCLUSIONS: Drotrecogin alfa (activated) is cost-effective in the treatment of severe sepsis with multiple organ failure when added to best standard care. The cost-effectiveness of the drug increases with baseline disease severity, but it remains cost-effective for all patients when used in compliance with the European approved indication.

Acute Disease↗

Role of hyperbaric oxygen exposure in reduction of lipid peroxidation and in multiple organ failure induced by zymosan administration in the rat.

The aim of the present study was to evaluate the effects of hyperbaric oxygen (HBO) therapy on multiple organ failure induced by zymosan. Administration of zymosan (500 mg/kg) in the rat induced neutrophil infiltration in the lung, liver, and intestine as evaluated by increase in myeloperoxidase (MPO) activity. Therefore, lipid peroxidation was significantly increased in zymosan-treated rats. This inflammatory process coincided with the damage of lung, liver, and small intestine. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine in the lung, liver, and small intestine of zymosan-shocked rats. HBO (2 absolute Atmosphere) exposure attenuates the increase in the tissue levels of MPO and malondialdehyde (MDA) caused by zymosan in the lung, liver, and intestine. In addition, HBO (2 absolute Atmosphere) was effective in preventing the development of lung, liver, and intestine injury. Taken together, the present results demonstrate that HBO may also be an efficacious treatment in multiple organ failure induced by zymosan.

Animals↗

[Hormonal changes and pituitary histological and immunocytochemical studies of patients with multiple organ failure].

OBJECTIVE: We investigated the correlation between the endogenous hormonal changes of pituitary-adrenal and pituitary-thyroid hormones and the prognosis of patients in multiple organ failure, and elucidated the mechanism of blunted thyrotropin (TSH) secretion by histological and immunocytochemical studies of anterior pituitary glands. PATIENTS: Forty-three patients were studied who had been admitted to the intensive care unit of Sapporo Medical University Hospital and had been diagnosed as having multiple organ failure. MEASUREMENTS: Pituitary adrenal hormones [corticotropin (ACTH), cortisol] and pituitary thyroid hormones [TSH, triiodothyronin (T3), free-T3, thyroxine (T4), free-T4, thyroxine-binding globulin (TBG)] were measured, and TSH and prolactin (PRL) responses thyrotropin-releasing hormone (TRH) were examined within 24 hours of admission to the ICU. Individual variables were compared between survivors (n = 19) and nonsurvivors (n = 24). Thirteen patients (five survivors, eight nonsurvivors) were investigated again before discharge from the ICU or death. Morphology was examined by hematoxilin-eosin staining, and avidin-biotin-peroxidase complex immunostaining was used to demonstrate the spectrum of TSH in 14 nonsurvivors. RESULTS: (1) ACTH levels remained within the normal range, while cortisol levels increased to above normal levels. Neither hormone showed significant differences between survivors and nonsurvivors. In nonsurvivors, cortisol levels decreased before death despite the increased ACTH levels. (2) T3 and free-T3 levels decreased markedly to below normal values, and reverse-T3 levels increased markedly to above normal values. Nonsurvivors showed significant differences in TSH, T4 and reverse-T3 levels compared with survivors. (3) TSH response to TRH was blunted in both groups but PRL response to TRH was normal. Nonsurvivors showed severely depressed TSH response. Nonsurvivors continued to show blunted TSH response to TRH, while this improved in survivors. (4) The histological study did not show very serious damages to anterior pituitary glands as TSH secretion was depressed. Many TSH immunoreactive cells were also observed by immunocytochemical study. CONCLUSION: Decreased cortisol, low T4 levels and blunted TSH response to TRH correlated with mortality in MOF patients. Histological and immunocytological studies suggest that blunted TSH secretion is not caused by pituitary damages or TSH exhaustion but by disturbances in TSH secretion. This blunted TSH secretion is reversible and its improvement is an indicator of survival.

Adrenocorticotropic Hormone↗