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Peripheral nerve function in sepsis and multiple organ failure.

Forty-three patients who had sepsis and multiple organ failure (critical illness) were studied prospectively to determine the incidence and severity of peripheral nerve function and to correlate such function with a number of variables. Electrophysiologic studies indicated a primary axonal degeneration of motor and sensory fibers in 30 (70 percent). Fifteen (30 percent) had the clinical signs of difficulty in weaning from assisted ventilation, weakness of limb muscles, and reduced or absent deep tendon reflexes. Full recovery from the polyneuropathy occurred among the 23 (53 percent) who survived, except three who had a very severe polyneuropathy. A peripheral nerve function index, computed from electrophysiologic measurements, showed statistically significant (p less than 0.01) negative correlations with the time in the critical care unit, and the serum glucose value; the serum albumin level showed a positive correlation. Multiple regression analyses indicated all three factors accounted for 47 percent (r2 = 0.4678) of all potential variables. In a separate analysis, the nerve function index correlated with the amplitude of the diaphragm compound muscle action potential (p less than 0.01). The results were consistent with the polyneuropathy being due to the same mechanisms that are currently postulated to cause dysfunction in this syndrome of other organ systems (including the neuromuscular respiratory system).

Bacterial Infections↗

Early predictors of postinjury multiple organ failure.

OBJECTIVE: To find a predictive model for postinjury multiple organ failure (MOF). DESIGN: A 3-year cohort study ending December 1992 (first year: retrospective; last 2 years: prospective). SETTING: Denver General Hospital (Colo) is a regional level I trauma center. PATIENTS: Consecutive trauma patients with an Injury Severity Score (ISS) greater than 15, with an age greater than 16 years, and who survived longer than 24 hours. Stepwise logistic regression analysis was performed in all patients (n = 394), in the subgroup of patients with 0 to 12 hours, plus 12 to 24 hours base deficit (BD) results (n = 220), and in a second subgroup of patients with BD plus lactate results at 0 to 12 hours and 12 to 24 hours (n = 106). MAIN OUTCOME: Postinjury MOF. RESULTS: The following variables were identified as independent predictors of MOF in the analysis of all patients: age more than 55 years, ISS greater than or equal to 25, and more than 6 U of red blood cells in the first 12 hours after admission (U RBC/12 hours). In the subgroup with BD results, the same analysis identified age greater than 55 years, greater than 6 U RBC/12 hours, and BD greater than 8 mEq/L (0 to 12 hours), while in the last subgroup analysis including BD and lactate results, greater than 6 U RBC/12 hours, BD greater than 8 mEq/L (0 to 12 hours), and lactate greater than 2.5 mmol/L (12 to 24 hours) were independently associated with MOF. CONCLUSIONS: Age greater than 55 years, ISS greater than or equal to 25, and greater than 6 U RBC/12 hours are early independent predictors of MOF. Subgroup analyses indicate that BD and lactate levels may add substantial predictive value. Moreover, these results emphasize the predominant role of the initial insult in the pathogenesis of postinjury MOF.

Adolescent↗

Quality of life after cardiac surgery complicated by multiple organ failure.

OBJECTIVE: To evaluate quality of life after prolonged multiple system intensive care treatment in cardiac surgical patients. DESIGN: A case-control study. SETTING: Adult 12-bed thoracic intensive care unit (ICU) at a university teaching hospital. PATIENTS: Forty-seven patients surviving multiple organ failure requiring intensive care treatment for > or = 5 days (ICU group). Patients with a completely uncomplicated postoperative course were matched to the study group with respect to gender, age, and type and date of surgery. The Nottingham Health Profile was used to assess quality of life at least 1 yr after complicated cardiac surgery. INTERVENTIONS: Quality of life measures were collected at least 1 yr after discharge from the ICU. MEASUREMENTS AND MAIN RESULTS: Seventy-five percent of the patients in the ICU group suffered from multiple organ failure involving at least three organ systems, with a mean stay in the ICU of 9.0 +/- 1.2 (SEM) days. Quality of life was considerably reduced in the ICU group, with a higher total mean score of all dimensions of quality of life (22.7 +/- 2.6) compared with the control group (13.2 +/- 2.4 [SEM])(p < .01). The Nottingham Health Profile score was higher in three of six dimensions of health--i.e., energy (p < .05), physical mobility (p < .05), and emotional reactions (p < .05)--compared with the control group. A higher percentage of patients reported problems in three of six important activities of daily life--housework (p < .05), hobbies (p < .01), and sex life (p < .01)--compared with the control group. CONCLUSION: Patients treated with prolonged multiple system intensive care after heart surgery have a poor outcome with respect to quality of life measured at least 1 yr after discharge from the ICU.

Adult↗

Postinjury multiple organ failure: role of extrathoracic injury and sepsis in adult respiratory distress syndrome.

Adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF) occur as a result of an unbridled systemic inflammatory response (i.e., severe systemic inflammatory response syndrome [SIRS]). Early epidemiologic studies concluded that infection with systemic sepsis was the common pathway for the development of ARDS and eventual MOF. As a consequence, research investigation from 1977 to 1987 focused on later clinical events (e.g., immunosuppression, persistent hypercatabolism, and bacterial translocation). Now, it is believed that an initial massive traumatic insult can create severe SIRS independent of infection (one-hit model). Alternatively, a less severe traumatic insult can create an inflammatory environment (i.e., primes the host) such that a later, otherwise innocuous, secondary inflammatory insult precipitates severe SIRS (two-hit model). As a result of these newer inflammatory models, research interest over the last 5 yrs has shifted to investigating earlier clinical events (e.g., unrecognized flow-dependent oxygen consumption, ischemia/reperfusion, and priming/activation of the inflammatory response). The traditional infection models of ARDS and MOF are applicable to current research and patient care efforts. However, the inflammatory models emphasize the pivotal role of the initial traumatic insult. Moreover, while ARDS occurs earlier than other types of overt organ failure, it is now believed that simultaneous organ injury is occurring, presumably via similar inflammatory mechanisms.

Adult↗

Multiple organ failure: clinical and experimental.

The clinical scenario of multiple organ failure (MOF) is reviewed and its frequent correlation with sepsis emphasized. It is hypothesized that MOF is produced by the formation of immune complexes (IC) in response to infection with deposition on organs such as the liver, lung, and kidney. Such immune complexes trap macrophages which can directly damage endothelium. Such a pathologic picture is in keeping with that of MOF. Granular deposits of IgG, IgM, C3, C5, and fibrinogen have been identified in the organs of four patients dying of MOF and sepsis. Similar deposits have been identified using fluorescent antibody stains in the organs of rabbits following cecal perforation. It is hypothesized that sepsis may produce organ failure at a distance from the site of infection via deposits of immune complexes.

Acute Kidney Injury↗

Do diets enriched with oil prevent multiple organ failure in mice?

OBJECTIVE: To examine the effects of various diets supplemented with fat in an experimental model of multiple organ failure in mice. DESIGN: Two randomised laboratory studies. SETTING: University hospital. MATERIAL: 177 female Swiss mice (weight 20-30 g). INTERVENTIONS: Experiment I: 59 mice; 20 received no dietary supplement, 20 received 15% palm oil, and 19 received 14% fish oil plus 1% corn oil, eight weeks before injection of 100 mg zymosan/100 g in 4 ml liquid paraffin; 5 mice in each group killed after 1.5 hours, and the rest on day 12. Experiment II: 118 mice; 29 received no dietary supplement, 30 received 15% palm oil, 30 1% corn oil, and 29 14% fish oil, 12 weeks before injection with zymosan. 20 mice in each group received streptomycin 5 g/l in drinking water starting five days before injection of zymosan and continued until the end of the experiment. All mice killed on day 12. MAIN OUTCOME MEASURES: Mortality, body and organ weights, and culture of peritoneal fluid. Detection of tumour necrosis factor-alpha (TNF-alpha) in plasma. RESULTS: Experiment I: only 5 control mice, 2 in the fish oil, and 7 in the palm oil, groups survived to day 12. Spleens in mice given fish oil were significantly heavier than those that had had palm oil (p = 0.03). Experiment II: 108/118 mice survived until day 12, and most had macroscopic signs of multiple organ failure. Liver weights in the fish oil group were lower than in the control (p = 0.04) and palm oil (p = 0.03) groups, and kidney weights higher than in the corn oil group (p = 0.007); there were no differences in the amounts of TNF-alpha detected in the blood. One culture in each experiment grew bacteria. CONCLUSION: Diets supplemented with fish oil did not prevent multiple organ failure or reduce plasma concentrations of TNF-alpha. Decontamination of the gut did not alter these results.

Animals↗

Septic shock and multiple organ failure.

OBJECTIVE: To assess the frequency and mortality rates of septic shock in ICU patients and the clinical course of multiple organ failure associated with septic shock. DESIGN: Retrospective case survey. SETTING: Tertiary care center. PATIENTS: During a 2-yr period, 2,469 consecutive intensive care patients were studied regarding the frequency and hospital mortality rates of septic shock. A subset of 1,311 patients was further analyzed for the occurrence of organ system failures within 48 hrs of the onset of septic shock and again 4 to 7 days later. MEASUREMENTS AND MAIN RESULTS: The frequency rate of septic shock was 1.9% (n = 48), with a mortality rate of 72.9% (n = 35) in patients with septic shock. Deaths due to septic shock represented 14.6% of all deaths in the ICU during the study period. Eighteen patients died within 72 hrs of the onset of septic shock. Refractory hypotension was the cause of death in 15 of these 18 patients. Beyond 72 hrs, multiple organ failure accounted for eight of 17 deaths. The mean +/- SD number of organ systems failing at 48 hrs was 3.3 +/- 1.3 in survivors and 4.0 +/- 1.1 in nonsurvivors, and at 4 to 7 days was 2.1 +/- 1.5 in survivors and 4.0 +/- 1.5 in nonsurvivors (p less than .05). None of the specific organ system failures had prognostic value. The number of organ system failures was not related to the duration of hypotension, but had a weak correlation (r2 = .26, p less than .05) with the duration of vasoactive treatment at 4 to 7 days. The prolonged need for norepinephrine therapy was associated with an increased occurrence of renal failure. Thirty (62.5%) patients had positive blood cultures and a mortality rate similar to the mortality rate of patients with negative blood cultures. Patients with negative blood cultures died more often with hypotension (p less than .02). CONCLUSIONS: Septic shock is a major cause of death in intensive care patients. Refractory hypotension is a main cause of early deaths. Later on, multiple organ failure becomes the primary clinical problem and cause of mortality.

Adult↗

[The role of nutrition on the treatment of septic syndrome and multiple organ failure].

Basing on current literature the issues regarding nutrition in patients with septic syndrome and multiple organ failure were discussed. It was emphasised that patient feeding along with providing metabolic substrates also serves as a treatment method. Diet ingredients in specific carbohydrate, protein and fat metabolism disorders were analysed. We focused upon the role of emulsion of fat, especially medium chain triglycerides (MCT) and -3-linolenic acid (fish oil). The unique role o f glutamine, arginine and branched chain amino acids (BCA) was highlighted. Patient nutrition with accordance to the presented new methods has become an efficient routine of treatment in septic syndrome. It may constitute an efficient prophylaxis against multiple organ failure.

Animals↗

[Severe pulmonary tuberculosis and multiple organ failure].

Thirty four cases of severe pulmonary tuberculosis complicated by multiple organ failure were reported. The failure usually started firstly from the lung (70.6%). The various organ failures occurred successively to the heart, brain, liver, kidney, stomach and intestines. The death rate is 58.8 percent. The standard of diagnosis and the measures of prevention and treatment were suggested.

Aged↗

Circulating interleukin-8 concentrations in patients with multiple organ failure of septic and nonseptic origin.

OBJECTIVES: Interleukin (IL)-8, a pro-inflammatory cytokine, is a potent chemoattractant factor and an activator of neutrophils produced by many cell types after stimulation by IL-1, tumor necrosis factor (TNF), or microbial products such as endotoxins. We investigated whether the presence of measurable IL-8 in plasma was associated with the clinical status of severely ill septic or nonseptic patients susceptible to the development of multiple organ failure. DESIGN: Cohort study. SETTING: A collaborative study between an intensive care unit and a research laboratory. SUBJECTS: Circulating IL-8 concentrations were measured in the plasma of 27 patients with sepsis syndrome and in 16 patients with noninfectious shock because these two conditions put patients at risk for the development of multiple organ failure. Sixteen of 27 patients with severe infection and 13 of 16 patients with noninfectious pathologies developed multiple organ failure. MEASUREMENTS AND MAIN RESULTS: A specific enzyme-linked immunosorbent assay (ELISA) for IL-8 was set up with a monoclonal and a rabbit polyclonal antihuman IL-8 using a sandwich technique. High concentrations of circulating IL-8 were found in the plasma of patients with sepsis syndrome. Among septic patients, a significant difference was observed between concentrations of IL-8 in survivors (n = 16) and nonsurvivors (n = 11) (81 +/- 13 pg/mL vs. 3326 +/- 1219 pg/mL, respectively; p = .001). A correlation was noticed between plasma IL-8 and IL-6 concentrations (r2 = .42; p = .001), while no correlation was observed between IL-8 and TNF-alpha values, or between IL-8 and IL-1 beta. Although the mortality rate of nonseptic, multiple organ failure patients was 92%, low plasma concentrations of IL-8 were found (78 +/- 34 pg/mL), while high plasma concentrations were measured in septic, multiple organ failure patients (mortality rate 69%) who were sampled at a similar stage. By contrast, increased IL-6 values were observed in both septic and nonseptic, multiple organ failure patients. CONCLUSIONS: In septic patients, high amounts of circulating IL-8 concentrations correlate with fatal outcome, whereas only low plasma concentrations of IL-8 are present in patients with nonseptic, multiple organ failure. This finding suggests that the signals involved in the exacerbation of IL-8 production are different, depending on infectious or noninfectious etiology.

Aged↗

A prospective clinical study on the pathogenesis of multiple organ failure in severely burned patients.

This study has shown that multiple organ failure (MOF) is one of the major causes of death in patients with severe burns. Both the plasma and visceral levels of TXB2 and the TXB2/6-keto-PGF1 alpha ratio were significantly increased. The changed plasma levels of TXB2 and the TXB2/6-keto-PGF1 alpha ratio paralleled the deterioration of the general condition in MOF patients. The circulatory platelet aggregation ratios (CPAR) in the MOF patients initially declined then dropped profoundly at 5-7 days postburn, indicating more microaggregate formation. CPK, LDH and GOT had increased markedly by 1 day, were elevated further at 2-3 days, and remained at supranormal levels for the first 7 days postburn. Degeneration, destruction, oedema, haemorrhage and thrombosis were observed in tissues from patients who died due to heart, lung, renal and hepatic failure. Clinically, 13 of the 16 MOF cases developed organ failure and 11 died between 3 and 7 days postburn. These findings confirmed that the increases of TXA2 and the TXA2/PGI2 ratio in plasma and visceral tissues can be an important factor in the genesis and development of postburn MOF.

6-Ketoprostaglandin F1 alpha↗

[The concept of the development of multiple organ failure in a model of gestosis].

Mechanisms of development of multiple organ failure (MOF) in gestosis have been studied. Analysis of the findings of examinations of 95 women with gestosis hospitalized in intensive care wards of Institute for Maternity and Neonatality Protection demonstrated that elements of the systemic inflammatory response syndrome (SIRS) underlie the development of MOF syndrome in gestosis, which can be diagnosed starting from early terms of gestation.

Adult↗

[Peripheral nerve conduction studies in patients with multiple organ failure].

INTRODUCTION: The polyneuropathy of critical diseases that often accompanies multiple organ failure (MOF) is one of the various causes that leads to the death of these patients. AIMS: To evaluate the electrophysiological behaviour of peripheral nerves in patients with MOF. Subjects and methods. A prospective cross sectional study was performed in 18 patients with MOF (the study group), 50 healthy subjects and 20 suffering from Guillain Barr Stroll Landry syndrome (GBS) (the control groups). All of them were submitted to sensory and motor peripheral nerve conduction studies. RESULTS: The aetiology of this syndrome was varied: 17 patients required mechanical ventilation and 15 had difficulty in weaning. The main electrophysiological alterations in the study group consisted in a drop in amplitude with prolonged latency and duration, and slowed conduction velocities for the sensory potentials of the median and posterior tibial nerves, while the lowered amplitude in motor nerve conduction was detected to a lesser degree and intensity. On comparing them with those obtained in GBS, statistically significant differences were found. The greatest electrophysiological alterations were detected in those who had difficulty in weaning those who presented an unfavourable evolution. CONCLUSIONS: Subjects with MOF were found to have a predominantly sensory peripheral axono myelinopathy which, on monitoring it electrophysiologically, allows us to establish a prognosis regarding severity, evolution and gradually cutting the dependence on mechanical ventilation

Multiple Organ Failure↗

Clinical studies on postburn multiple organ failure: its aetiological factors and monitoring.

This study demonstrated that multiple organ failure (MOF) developed in 16 of 57 severely burned patients (28.1 per cent). When expressed as a percentage of the 590 patients admitted during the same period, the incidence became 2.7 per cent. Fifteen of the 16 MOF cases died, with a mortality of 93.8 per cent. In those patients with TBSA over 80 per cent with inhalation injury, severe shock and systemic infection, the incidence of MOF was significantly higher. Systemic infection and severe shock were the most important complications. These results indicated that the severity of the burn is the prime prerequisite of MOF, while severe shock and systemic infection are secondary but very important factors in the genesis and development of postburn MOF. The circulatory platelet aggregate ratio (CPAR) started to decrease significantly at 12 h postburn, remaining at low levels and declining further at 5-7 days postburn. However the values of the myocardial enzyme spectrum (MES) remained at significantly higher levels, indicating significant and continuous increases of microaggregate formation and the continuous existence of visceral and tissue ischaemia and cellular destruction. Changes of CPAR and MES in MOF patients were directly related to the development of MOF. It is advisable to use CPAR and MES to monitor the possible development of postburn MOF.

Adult↗

[Pulmonary gas exchange function during hemofiltration in patients with multiple organ failure].

Pulmonary gas exchange was examined in 37 patients with multiple organ failure in the course of long forced ventilation of the lungs (FVL) and hemofiltration (HF). Acute respiratory distress syndrome (ARDS) was observed in 25 (65.7%) patients. Assessment of the effect of HF on the lungs for the entire group and for patients with ARDS showed no changes in the pulmonary gas exchange function in the course of 24-hour HF. On the other hand, during the first 7-8 h of HF the oxygenation function of the lungs either improved (group 1, n = 11) or deteriorated (group 2, n19). In group 1 the paO2 reliably (by 36%) increased, paO2/FiO2 increased by 36%, (A-a)O2 reliably (16%) dropped, as did the Os/Ot (by 30%) during 7-8 hours. In group 2 PaO2 decreased by 14%, PaO2/FiO2 by 16%, and the oxygen index (O2I) increased by 24% (p < 0.05), these values remaining at levels requiring no more intensive respiratory support or other intensive care. Gas exchange function of the lungs was studied in 18 patients in the course of isotonic dehydration. The pulmonary capillaries wedge pressure dropped by 25%, central venous pressure by 18% in the course of dehydration. Changes in other values were unreliable. Due to decrease of extracellular hyperhydration the alveolar-arterial O2 gradient dropped by 17.5% and the intrapulmonary shunt by 21% (p < 0.05). Oxygen tension in the arterial blood remained the same in the group in general.

Central Venous Pressure↗

Blood transfusion and the two-insult model of post-injury multiple organ failure.

Neutrophils (PMNs) have been implicated in the pathogenesis of multiple organ failure (MOF). The two-insult model of MOF is based on the fundamental concept that two sequential and independent insults that are individually innocuous against the host can cause overwhelming inflammation. The in vitro PMN priming/activation sequence simulates the two-insult model. Our work has demonstrated that transfusion is an early consistent risk factor for post-injury MOF and lysophosphatidylcholines (lyso-PCs) are generated in stored blood components. Additionally, platelet-activating factor (PAF) is a key inflammatory agent produced in severely injured patients. We therefore hypothesize that two events, trauma and transfusion, enhance PMN cytotoxicity irrespective of the sequence. Superoxide (O2-) production was measured by reduction of cytochrome c, adherence to fibrinogen was assessed by the radioactivity of adherent Na2(51)CrO4 (51Cr)-labeled PMNs, and endothelial cell (EC) damage by measuring the radioactivity released from 51Cr-labeled human umbilical vein endothelial cells monolayers. Isolated PMNs were primed with buffer, PAF (2 microM), or lyso-PCs (4.5, 15, and 30 microM) followed by activation with buffer, N-formyl-methionyl-leucyl-phenylalanine (fMLP) (1 microM), PAF (2 microM), or lyso-PCs (4.5, 15, and 30 microM). Neither PAF nor lyso-PCs alone stimulated O2- production. While PAF alone caused PMN adherence, lyso-PCs alone did not allowed PMNs to adhere to fibrinogen. However, both combinations of PAF/lyso-PCs and lyso-PCs/PAF significantly augmented O2- production and PMN adherence. Furthermore, these enhanced PMN cytotoxic responses significantly caused EC damage. These findings suggest that in the scenario of the two-insult model, early or late transfusion administered following trauma can provoke PMN cytotoxicity via priming or activation, thereby increasing the risk of post-injury MOF.

Blood Preservation↗

Does disseminated intravascular coagulation lead to multiple organ failure?

Microvascular dysfunction with its associated impaired regional oxygen transport and use is believed to be the final common pathway in the development of multiple organ failure. The precise mechanisms underlying this dysfunction, however, are uncertain. Activation of the coagulation system is a key feature in the pathogenesis of sepsis, but whether it is also the cause of multiple organ failure is unclear. This article discusses the evidence for and against a key role for disseminated intravascular coagulation in the pathogenesis of multiple organ failure.

Disseminated Intravascular Coagulation↗