Value of Superoxide Dismutase for Prevention of Multiple Organ Failure After Multiple Trauma

Marzi, Ingo; Bühren, V.; Schüttler, A.; Trentz, O

doi:10.1097/00005373-199307000-00018

Cited by 51 publications

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“…While many of these agents have been proven effective in controlled animal models, they have failed to alter outcome when applied in the clinical arena. 1,[11][12][13][14][15][16][17][18] Many of the implicated inflammatory mediators are regulated by intracellular signaling cascades involving the mitogen-activated protein kinases (MAPK). 19 -24 One prominent member, p38, mediates the signal transduction induced by many environmental stresses, such as endotoxin and osmotic stress.…”

Section: Discussionmentioning

confidence: 99%

“…modulatory agents that, though failing to improve outcome for the entire population, do significantly affect survival for specifically defined subsets. 1,18,48,51 Hence, the failure of these therapies in the overall population may stem from a lack of ability to identify the group of patients for whom they are best suited. Incorporating the analysis of markers of the host inflammatory state into prognosis scoring systems may minimize this error.…”

Section: Discussionmentioning

confidence: 99%

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Mitogen-Activated Protein Kinases in the Intensive Care Unit: Prognostic Potential

Rosengart¹,

Nathens²,

Arbabi³

et al. 2003

Annals of Surgery

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ObjectiveTo evaluate the prognostic significance of the activational status of p38, specifically progression to multiple organ dysfunction syndrome (MODS), in a group of severely injured trauma patients. Summary Background DataTo date, therapeutic manipulation of the host immunoinflammatory response has not affected the outcome of patients with MODS. A major concern is the inability to identify the patient most at risk so as to enable early intervention. MethodsNineteen trauma patients underwent bronchoalveolar lavage (BAL). Cells obtained were plated, stimulated with lipopolysaccharide (LPS), and then harvested at varying time points after stimulation. p38 was evaluated by Western blot. ResultsNineteen patients were categorized into two groups according to baseline and LPS-stimulated p38 activation in cells obtained by BAL. Group 1 demonstrated a 10-fold increase in p38 activation with LPS treatment over unstimulated controls. Group 2 had high baseline levels of p38 that were unresponsive to subsequent LPS stimulation. Both groups were similar with respect to age, gender, shock (systolic blood pressure Ͻ 90), Injury Severity Score, APACHE II, lactate levels, base deficit, blood transfusions, and the cell differential of BAL fluid. However, patients in group 2 had a greater incidence of progression to MODS as defined by the Marshall MOD score, a longer duration of mechanical ventilation, a longer stay in the intensive care unit, and a longer overall hospital stay than group 1. ConclusionsThese results demonstrate the prognostic significance of p38 activation in predicting outcome in critically ill trauma patients. Furthermore, these results demonstrate that trauma populations identical by current scoring systems contain a mixture of patients with markedly different outcomes as identified by p38 activation. Measurement of p38 may enable early identification of a subgroup of patients at increased risk for MODS to permit effective therapeutic intervention.Multiple organ dysfunction syndrome (MODS) is the predominant cause of late death in patients requiring intensive care. Most consider it the pathologic sequela of an excessive host inflammatory response. The failure of current therapeutic interventions focused on the host's immunoinflammatory response to affect the outcome of MODS stems, in part, from an incomplete understanding of the complex underlying pathophysiology and an inability to identify early the patients at greatest risk for development of MODS.1 In the severely injured patient, our ability to predict many important outcomes is limited. Current scoring systems, such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, use population-based analyses and require the acquisition of many variables to compute a mathematical model to derive a numerical score indicative of outcome.2-10 These scores define the net physiologic state of a heterogeneous population and, while valuable in estimating overall population mortality, correlate poorly with other important morbidity endpoints. Moreo...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mitogen-Activated Protein Kinases in the Intensive Care Unit: Prognostic Potential

Rosengart¹,

Nathens²,

Arbabi³

et al. 2003

Annals of Surgery

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“…The release of superoxide radicals in the process of renal I/R plays an important role in tissue damage [4,5]. Although scavengers for reactive oxygen species reduce the extent of renal injury during I/R in animal studies [10,11], superoxide dismutase (SOD) is somewhat problematic in its clinical employment because of its short half-life and its low accumulation in the vital organs [13,14]. Moreover, in vivo SOD might exert its protective effect by inhibition of neutrophil-mediated free radical production and thus indirectly reduce the severity of postischemic reperfusion injury.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Effect of Zinc on Acute Renal Failure Induced by Ischemia-Reperfusion Injury in Rats

Ogawa¹,

Mimura²

1999

Am J Nephrol

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Zinc may have an antioxidant effect mediated by induction of metallothionein. Based on the assumption that metallothionein can scavenge oxygen free radicals, we examined whether zinc administration prior to renal ischemia would improve renal dysfunction caused by ischemia-reperfusion injury in rats. Wistar rats weighing 265 g were treated with an intraperitoneal injection of 20 mg/kg zinc 24 h prior to the renal ischemia-reperfusion procedure, which was achieved by a 30-min clamping of the bilateral renal vessels and subsequent 90-min reperfusion. Thirty-minute renal clearance tests were performed before and after renal ischemia in zinc- (n = 11) and saline-treated (n = 8) rats. Thiobarbituric acid reactive substance, conjugated diene, and metallothionein levels in the renal tissues were also determined. Sham-operated rats (n = 5 in each treatment) served as control for the ischemia-reperfusion rats. Ischemia-reperfusion resulted in significantly lower glomerular filtration rate values and marked increases in tissue concentrations of thiobarbituric acid reactive substance and conjugated diene compared with sham-operation. Zinc administration improved the reduced glomerular filtration rate values seen after the ischemia-reperfusion procedure, but not to the extent of pre-ischemic levels. Zinc pretreatment significantly reduced the increased levels of thiobarbituric acid reactive substance and conjugated diene during ischemia-reperfusion and increased metallothionein levels compared with saline injection. These findings suggest that zinc has an antioxidant effect mediated through the induction of metallothionein, but appears only to have a minor protective effect on renal function induced by renal ischemia-reperfusion injury.

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“…The development of multiple organ dysfunction after trauma involves numerous humoral and cellular inflammatory systems with overlapping stimulation and suppression throughout the posttraumatic course [7,26]. Sauaia et al [27] proposed some prognostic determinants for the manifestation of posttraumatic organ dysfunction and failure: ISS > 25 points, age ≥ 55 years, initial requirement of > 6 blood units/12 h, blood lactate > 2.5 mmol/l (12-24 h), and base excess < -8 mmol/l (0-12 h).…”

Section: Discussionmentioning

confidence: 99%

Circulating Inflammatory and Metabolic Parameters to Predict Organ Failure after Muliple Trauma

Frank

Maier

Koenig

et al. 2002

European Journal of Trauma

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Background: Patients encountering severe trauma are at high risk of sequential organ complications. We studied the value of circulating inflammatory mediators and metabolic parameters to evaluate their predictive value with respect to the development of multiple organ failure (MOF). Patients and Methods: In 77 traumatized patients with a mean Injury Severity Score (ISS) of 28.8 ± 1.1 points, Creactive protein (CRP), polymorphonuclear (PMN) elastase, lactate, interleukin-6 (IL-6), IL-8, and soluble tumor necrosis factor receptors 1 and 2 (TNF-R1 and TNF-R2) were determined for a period of 11 days following multiple trauma. Results: Weak and moderate correlations were found between mean plasma concentrations of all parameters and mean MOF scores calculated from the whole observation period [range: lactate (r = 0.31, p < 0.01) to TNF-R1 (r = 0.53, p < 0.001)]. Daily TNF-R1 and lactate concentrations of the 1st week moderately correlated with mean MOF scores of the 2nd week (p < 0.01). ISS weakly correlated with all parameters except lactate [range: IL-8 (r = 0.27, p < 0.05) and PMN elastase (r = 0.46, p < 0.001)]. Prediction of MOF could not be improved by inclusion of several or all investigated mediators into multiple regression models. Conclusion: Only early plasma TNF-R1 and blood lactate concentrations showed a moderate association with the development of late posttraumatic organ failure. Thus, the predictive role of inflammatory mediators with respect to the manifestation of organ dysfunction after severe trauma seems limited.

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Value of Superoxide Dismutase for Prevention of Multiple Organ Failure After Multiple Trauma

Cited by 51 publications

References 0 publications

Mitogen-Activated Protein Kinases in the Intensive Care Unit: Prognostic Potential

Mitogen-Activated Protein Kinases in the Intensive Care Unit: Prognostic Potential

Antioxidant Effect of Zinc on Acute Renal Failure Induced by Ischemia-Reperfusion Injury in Rats

Circulating Inflammatory and Metabolic Parameters to Predict Organ Failure after Muliple Trauma

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