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Sepsis

 

1: Med Klin 1999 Oct 15;94 Suppl 3:54-7

[Significance of selenium in intensive care medicine. Clinical studies of patients with SIRS/sepsis syndrome].

[Article in German]

Gartner R, Angstwurm M.

Medizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians-Universitat Munchen. This email address is being protected from spambots. You need JavaScript enabled to view it.

Selenium is an essential component of the intracellular antioxidant system as a structural component of the active center of the glutathione peroxidase enzymes. These selenoenzymes play a major role in protecting cells against peroxidation, especially lipid peroxidation and selenium seems to play a direct role in the regulation of inflammatory processes. In conditions of systemic inflammatory response or sepsis, patients are exposed to severe oxidative stress. These patients already have both, a decreased plasma selenium and glutathione peroxidase activity at admission to the ICU as has been shown in several studies. The degree of selenium deficiency is correlated with the severity of disease and the incidence of mortality. The reason for the low plasma selenium levels is unknown. Especially it would be of interest a) if the low plasma selenium is the consequence of the systemic inflammatory response with distribution of selenium in other compartments of the body, b) most important, whether the substitution of selenium might improve the outcome and decrease the mortality rate of these patients. In 2 independently performed intention-to-treat studies including patients with systemic inflammatory response syndrome or sepsis a beneficial effect of selenium supplementation on multiple organ function and outcome could already be demonstrated as well as a tendency of an improved mortality rate. A prospective analytical study clearly could demonstrate the inverse relationship between low plasma selenium and morbidity and mortality of patients with SIRS/sepsis. The results of these studies are so convincing, that we propose a randomized, prospective, double blind multicenter phase-III study including patients with systemic inflammatory response syndrome or sepsis to investigate, whether a high-dose selenium substitution in addition to the recommended treatment strategies for patients with sepsis improves outcome and mortality rate of these patients.

Publication Types: Review Review, tutorial

PMID: 10554531 [PubMed - indexed for MEDLINE]

1: Crit Care Med 2000 Jan;28(1):143-9

Comment in: Crit Care Med. 2000 Jan;28(1):275-9

Protein carbonyl measurements show evidence of early oxidative stress in critically ill patients.

Winterbourn CC, Buss IH, Chan TP, Plank LD, Clark MA, Windsor JA.

Department of Pathology, Christchurch School of Medicine, NZ.

OBJECTIVE: To determine whether there is evidence of oxidative injury in patients who are critically ill with severe sepsis or major trauma, by measuring protein and lipid oxidation products. DESIGN: A prospective, observational study. SETTING: Critical care unit at a university teaching hospital. PATIENTS: Twenty-two patients with severe sepsis (Acute Physiology and Chronic Health Evaluation II score 15-34) and eight patients with major trauma (Injury Severity Score 26-50). INTERVENTIONS: Plasma and bronchoalveolar lavage fluid was collected regularly during the first 10 days after trauma or onset of sepsis. Both fluids were analyzed for protein carbonyl concentrations as a measure of protein oxidation and thiobarbituric acid-reactive substances as a measure of lipid peroxidation. Myeloperoxidase concentrations were measured as an index of neutrophil activation. MEASUREMENTS AND MAIN RESULTS: Protein carbonyl concentrations were initially highly elevated compared with those in healthy adults in the plasma of both patient groups. They fell significantly within the first few days but remained above control values. Protein carbonyl concentrations were also high initially in bronchoalveolar lavage fluid and fell significantly with time. Thiobarbituric acid-reactive substances were not increased in plasma, and varied over a wide concentration range in lavage fluid. Myeloperoxidase activity reached micromolar levels in the lavage fluid when corrected for dilution, and was significantly higher in the plasma of the sepsis patients who subsequently died. There was a strong correlation between carbonyl concentrations in lavage fluid and plasma, and between protein carbonyls, thiobarbituric acid-reactive substances and myeloperoxidase in the lungs. CONCLUSIONS: Our results provide evidence of oxidation occurring early in severe sepsis and major trauma patients, with protein carbonyl measurements providing a sensitive index of this process. High protein carbonyl concentrations in plasma as well as bronchial aspirates indicate that oxidation is not restricted to the lungs. The correlation between oxidative measures and myeloperoxidase concentrations in the lung indicates that neutrophil oxidants could be responsible for the injury.

PMID: 10667514 [PubMed - indexed for MEDLINE]

1: Panminerva Med 2001 Mar;43(1):27-31

Oxidative stress status: possible guideline for clinical management of critically ill patients.

Bela P, Bahl R, Sane AS, Sawant PH, Shah VR, Mishra VV, Trivedi HL.

Departments of Biochemistry, Anaesthesiology, Institute of Kidney Disease and Research Centre Ahmedabad, India.

BACKGROUND: Critical care medicine has developed in the last few years into a separate scientific discipline and studies related to the outcome after intensive care usually suggest a long hospital stay that becomes cost prohibitive. The majority of problems (death) amongst critically ill patients requiring critical care involve sepsis, inflammation, tissue damage-oxidative stress, oxygen tension PO2, lipid peroxidation. The present investigation involves monitoring of serum levels of MDA, SOD as a possible guideline for severity of clinical situations in critically ill patients. METHODS: Fifty critically ill heterogeneous patients requiring intensive care in the ICU of IKDRC were selected as subjects with ages varying from 17 to 75 years. Serum levels of MDA (ng/ml), SOD (U/ml) were determined right from admission to discharge due to improvement / DAMA / death. MDA and SOD were estimated according to the methods of Buege and Aust et al. (1978), Nandi and Chatterji (1988). RESULTS: Critically ill patients irrespective of the disease process indicated significantly very high serum levels of MDA and low levels of SOD at the time of admission (13.28+/-4.26 ng/ml, 3.80+/-2.60 U/ml, respectively) according to the severity of the prevalent clinical situation. The pattern of serum levels of MDA and SOD according to subsequent clinical performance did indicate a decreasing trend of MDA (oxidant) and fluctuating trend of SOD (antioxidant enzyme except in those who inevitably succumbed to death in spite of adequate clinical management. CONCLUSIONS: The results of the present study have amply revealed the utility and relevance of monitoring oxidative stress in critically ill patients as biochemical markers, cost-effectiveness and role in decision making (withdrawal/continuation of different support modalities) as deemed fit.

PMID: 11319515 [PubMed - indexed for MEDLINE]

1: Circ Shock 1985;16(4):383-93

Role of free oxygen radicals in the development of gastrointestinal mucosal damage in Escherichia coli sepsis.

Arvidsson S, Falt K, Marklund S, Haglund U.

Live Escherichia coli were infused into anesthetized cats given 0.6 ml bile/kg and 80 mM HCl into the stomach. Systemic and pulmonary arterial blood pressures, cardiac output, and gastric blood flow were monitored. Gastrointestinal total wall and mucosal blood flow were measured by microspheres. The microscopic mucosal damage was graded 0-4 (stomach) or 0-5 (intestine). One group of cats (N = 8) received 5 mg yeast CuZn superoxide dismutase (SOD) as a bolus before bacteria followed by infusion 50 mg/3 hr. Four of these cats were also given catalase in the same dose. Controls (N = 8) had no treatment. After 3 hr gastric ulceration (grades 2-4) was found in controls but only in 50% of treated cats (P less than 0.1). About 50% and 25% of the cats in both groups developed significant small intestinal and colonic mucosal damage, respectively. SOD or SOD/catalase had no effect on late systemic hypotension, decrease in cardiac output, or transient increase in pulmonary pressure. Total gastric blood flow did not change, while at late sepsis gastric mucosal flow was decreased in the treated group. Small intestinal mucosal flow decreased in both series. It is concluded that free oxygen radicals may be of partial importance in the development of sepsis-induced gastric, but not intestinal, mucosal damage.

PMID: 3915236 [PubMed - indexed for MEDLINE]

1: J Clin Invest 1984 Aug;74(2):608-13

Oxygen metabolites stimulate thromboxane production and vasoconstriction in isolated saline-perfused rabbit lungs.

Tate RM, Morris HG, Schroeder WR, Repine JE.

Generation of reactive oxygen metabolites, thromboxane increases, and vasoconstriction have been implicated in the pathogenesis of acute edematous lung injury, such as that seen in patients with the Adult Respiratory Distress Syndrome (ARDS), but their interactions are unknown. We hypothesized that reactive O2 products would stimulate arachidonic acid metabolism in lungs and that vasoactive products of arachidonate, such as the potent vasoconstrictor thromboxane A2, might then mediate O2-metabolite-induced pulmonary vasoconstriction. We found that O2 metabolites generated by injection of purine plus xanthine oxidase caused increases in mean pulmonary artery perfusion pressures (27 +/- 4 mmHg) in isolated perfused lungs. In addition, purine plus xanthine oxidase also caused 30-fold increases in perfusate levels of thromboxane B2 (the stable metabolite of thromboxane A2) compared with only twofold increases in 6-keto-PGF1a (the stable metabolite of prostacyclin). Moreover, prior addition of catalase inhibited both vasoconstriction and the thromboxane B2 production seen in isolated lungs following injection of purine plus xanthine oxidase. Similarly, pretreatment with cyclooxygenase inhibitors, either aspirin or indomethacin, also completely blocked thromboxane generation and markedly attenuated pressor responses usually seen after purine plus xanthine oxidase (increase in mean pulmonary artery perfusion pressures, 4.4 +/- 1.5 mmHg). Furthermore, imidazole, a thromboxane synthetase inhibitor, also decreased O2-metabolite-induced thromboxane generation and vasoconstriction. These results suggested that thromboxane generation might participate in O2-metabolite-induced vasoconstriction. However, since a significant correlation between thromboxane levels and the degree of vasoconstriction could not be demonstrated, and since addition of superoxide dismutase reduced thromboxane generation but did not affect the intensity of vasoconstriction, it is possible that thromboxane is not the only vasoactive mediator in this model. We conclude that exposing lungs to O2 metabolites results in thromboxane generation and that thromboxane is a major mediator of oxidant-induced vasoconstriction.

PMID: 6547730 [PubMed - indexed for MEDLINE]

1: Circ Shock 1988 Aug;25(4):319-23

Oxygen free radical activity during live E. coli septic shock in the dog.

Morgan RA, Manning PB, Coran AG, Drongowski RA, Till GO, Ward PD, Oldham KT.

Shock Research Laboratory, Mott Children's Hospital, Ann Arbor, MI 48109.

Free radicals generated during purine catabolism or by activated granulocytes cause tissue injury by peroxidation of lipid membranes. In a canine model of sepsis initiated by intravenous live Escherichia coli, fluorescent products of lipid peroxidation (FP) were measured in serum. Four groups of five dogs infused with 10(9)E. coli/kg were analyzed--I: no further treatment; II: prior depletion of granulocytes with a cytotoxic antibody; III: pre-treatment with superoxide dismutase and catalase; and IV: resuscitation after bacterial infusion to maintain cardiac output greater than 80% of pre-bacteremic levels. In Groups I, II, and III, cardiac output fell to less than 50% of baseline within 1 hr and remained there throughout the study. FP in Groups I and II rose to greater than 200% of baseline (P less than .02 and less than .03). In Groups III and IV, FP did not rise significantly from baseline. The rise in serum FP and the prevention of this rise by-treatment with antioxidants indicate generation of oxygen radicals. Their presence had no effect on hemodynamic parameters. Granulocyte depletion did not alter appearance of FP; however, prevention of low cardiac output blocked FP formation. These data suggest that oxygen free radicals were generated by tissue ischemia, rather than by granulocytes, in this model of septic shock.

PMID: 3048773 [PubMed - indexed for MEDLINE]

1: Free Radic Res 1994 May;20(5):289-98

Oxidative damage to plasma proteins in adult respiratory distress syndrome.

Quinlan GJ, Evans TW, Gutteridge JM.

Department of Anaesthesia & Intensive Care, Royal Brompton National Heart and Lung Hospital, National Heart and Lung Institute, London, UK.

There is evidence that patients with adult respiratory distress syndrome are under severe oxidative stress that leads to molecular damage. Oxidative stress appears to be inherent in the disease process as well as an unfortunate complication of essential treatment with oxygen. Eight critically ill patients with an established diagnosis of adult respiratory distress syndrome requiring high inspired oxygen concentrations administered by ultra high frequency jet ventilation, were studied. Three patients survived (38%). For the group as a whole, there was evidence of increased protein damage, measured on serial plasma samples as an increase in protein carbonyls (mean +/- SEM, 1.41 +/- 0.09 nmol/mg protein), compared with Intensive Care Unit (ICU) controls (1.24 +/- 0.09 nmol/mg protein), and normal healthy controls (0.940 +/- 0.04 nmol/mg protein). Protein thiol groups were decreased in the ARDS group (4.56 +/- 0.50 nmol/mg protein) compared with ICU controls (5.5 +/- 0.27 nmol/mg protein), and the normal healthy controls (6.55 +/- 0.52 nmol/mg protein). However, when ARDS patients were grouped as survivors and non-survivors, total plasma protein levels were lower in survivors (53.9 +/- 2.15 mg/ml) compared with non-survivors (78.2 +/- 4.68 mg/ml); but the protein thiol content was significantly higher (p = < 0.001) in survivors (6.24 +/- 0.09 nmol/mg protein) compared with non-survivors (3.56 +/- 0.16 nmol/mg protein). Serial plasma measurements of protein damage indicated two different patterns. Survivors had higher total plasma thiol values (protein corrected), which increased as the lung injury resolved, and failing protein carbonyl values. By contrast, non-survivors had low and failing protein thiols often accompanying rising carbonyls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 8069386 [PubMed - indexed for MEDLINE]

1: Thorax 1994 Jul;49(7):707-10

Transient iron overload with bleomycin detectable iron in the plasma of patients with adult respiratory distress syndrome.

Gutteridge JM, Quinlan GJ, Evans TW.

Department of Anaesthesia and Intensive Care, Royal Brompton Hospital, London.

BACKGROUND--A retrospective study was conducted to evaluate iron status in plasma samples collected from five patients with the adult respiratory distress syndrome (ARDS) who had bleomycin detectable iron in at least one sample. Ten patients with ARDS with no evidence of bleomycin detectable iron and 10 healthy individuals served as controls. METHODS--Evidence of iron overload was established by measuring the percentage saturation of plasma transferrin. In each case the bleomycin assay for redox active, chelatable iron was used to measure plasma levels of non-transferrin bound iron in the low micromolar range; assays for total plasma iron and transferrin were performed to establish a diagnosis of transient iron overload. The effect of this on the ability of transferrin to act as a plasma antioxidant was assessed using two different assay systems. RESULTS--The five patients with evidence of transient iron overload (mortality 4/5) represented 33% of the total population of patients with ARDS (mortality 5/10) managed by the unit during the study period. All had low molecular mass iron detectable in their plasma and had clinical and biochemical evidence of multiorgan system failure as well as liver impairment. Compared with the ARDS and normal control populations, transferrin and albumin levels were low and the former failed to act as a plasma antioxidant in preventing free radical mediated damage to detector molecules. CONCLUSIONS--Patients with ARDS are thought to be under severe oxidative stress from their disease and from treatment with high inspired oxygen concentrations. A subgroup of patients with ARDS has been identified who displayed evidence of transient iron overload as a result of which their plasma iron binding antioxidant protection was greatly compromised. This finding must be considered a serious additional risk factor for oxidative stress.

PMID: 7520607 [PubMed - indexed for MEDLINE]

1: Crit Care Clin 1996 Jul;12(3):667-76

Nutrition support is not beneficial and can be harmful in critically ill patients.

Marino PL, Finnegan MJ.

University of Pennsylvania, School of Medicine, Philadelphia, USA.

The introductory remark by Lucretius serves as a reminder that nutrient intake can have very different consequences in different subjects. In the patient with an acute or serious illness, metabolic derangements can transform a substance that is normally a source of energy into a source of metabolic toxins. The potential for organic nutrients to become organic toxins in the diseased host is a phenomenon that deserves more attention in the debate about the value of nutrition support in critically ill patients.

Publication Types: Review Review, tutorial

PMID: 8839598 [PubMed - indexed for MEDLINE]

1: J Am Diet Assoc 1998 Sep;98(9):1001-8

Oxidative stress in critical care: is antioxidant supplementation beneficial?

Oldham KM, Bowen PE.

Mt Sinai Hospital Medical Center, Chicago, IL 60608, USA.

Reactive oxygen species (ROS) are constantly produced in human beings under normal circumstances. Antioxidant systems help defend the body against ROS but may be overwhelmed during periods of oxidative stress, which can cause lipid peroxidation, damage to DNA, and cell death. Critical illness, such as sepsis or adult respiratory distress syndrome, can drastically increase the production of ROS and lead to oxidative stress. Sources of oxidative stress during critical illness include activation of the phagocytic cells of the immune system (the respiratory burst), the production of nitric oxide by the vascular endothelium, the release of iron and copper ions and metalloproteins, and the vascular damage caused by ischemia reperfusion. Only indirect measurements of ROS are available, but the presence of oxidative stress in critical illness is supported by clinical studies. In general, serum antioxidant vitamin concentrations seem to decrease and measures of oxidative stress seem to increase in critically ill populations. Oxidative stress has been associated with sepsis, shock, a need for mechanical ventilation, organ dysfunction, acute respiratory distress syndrome, disseminated intravascular coagulation, surgery, and the presence of an acute-phase response. In addition, higher levels of oxidative stress seem to occur in patients with more notable injuries. Dietary supplementation with antioxidant vitamins seems to be the logical answer to decreasing serum antioxidant concentrations, but antioxidants may have adverse effects. The benefit of supplementing antioxidants in critically ill populations has not been shown and requires further study.

Publication Types: Review Review, tutorial

PMID: 9739800 [PubMed - indexed for MEDLINE]

1: Crit Care Med 2000 Jan;28(1):143-9

Comment in: Crit Care Med. 2000 Jan;28(1):275-9

Protein carbonyl measurements show evidence of early oxidative stress in critically ill patients.

Winterbourn CC, Buss IH, Chan TP, Plank LD, Clark MA, Windsor JA.

Department of Pathology, Christchurch School of Medicine, NZ.

OBJECTIVE: To determine whether there is evidence of oxidative injury in patients who are critically ill with severe sepsis or major trauma, by measuring protein and lipid oxidation products. DESIGN: A prospective, observational study. SETTING: Critical care unit at a university teaching hospital. PATIENTS: Twenty-two patients with severe sepsis (Acute Physiology and Chronic Health Evaluation II score 15-34) and eight patients with major trauma (Injury Severity Score 26-50). INTERVENTIONS: Plasma and bronchoalveolar lavage fluid was collected regularly during the first 10 days after trauma or onset of sepsis. Both fluids were analyzed for protein carbonyl concentrations as a measure of protein oxidation and thiobarbituric acid-reactive substances as a measure of lipid peroxidation. Myeloperoxidase concentrations were measured as an index of neutrophil activation. MEASUREMENTS AND MAIN RESULTS: Protein carbonyl concentrations were initially highly elevated compared with those in healthy adults in the plasma of both patient groups. They fell significantly within the first few days but remained above control values. Protein carbonyl concentrations were also high initially in bronchoalveolar lavage fluid and fell significantly with time. Thiobarbituric acid-reactive substances were not increased in plasma, and varied over a wide concentration range in lavage fluid. Myeloperoxidase activity reached micromolar levels in the lavage fluid when corrected for dilution, and was significantly higher in the plasma of the sepsis patients who subsequently died. There was a strong correlation between carbonyl concentrations in lavage fluid and plasma, and between protein carbonyls, thiobarbituric acid-reactive substances and myeloperoxidase in the lungs. CONCLUSIONS: Our results provide evidence of oxidation occurring early in severe sepsis and major trauma patients, with protein carbonyl measurements providing a sensitive index of this process. High protein carbonyl concentrations in plasma as well as bronchial aspirates indicate that oxidation is not restricted to the lungs. The correlation between oxidative measures and myeloperoxidase concentrations in the lung indicates that neutrophil oxidants could be responsible for the injury.

PMID: 10667514 [PubMed - indexed for MEDLINE]

1: Crit Care Med 1985 Mar;13(3):143-50

Quantitative analysis of polymorphonuclear leukocyte superoxide anion generation in critically ill children.

Zimmerman JJ, Shelhamer JH, Parrillo JE.

Apart from its well-known bactericidal action, superoxide anion produced by activated polymorphonuclear leukocytes is believed to be involved in pathophysiology of diffuse capillary leak syndromes, e.g., adult respiratory distress syndrome and septic shock. Neutrophil NADPH oxidoreductase, the superoxide anion synthetase, was assayed in blood samples from a variety of critically ill children. Neutrophils from patients with evidence of diffuse capillary leak syndrome had significantly depressed enzyme specific activity as compared to neutrophils from healthy controls or intensive care patients without evidence of diffuse capillary leak. These data along with additional in vitro findings support the contention that previously activated granulocytes may be refractory to subsequent activation, and that such behavior may represent an intrinsic defense mechanism to minimize inflammatory amplification autoinjury.

PMID: 2982544 [PubMed - indexed for MEDLINE]

1: Anaesthesiol Reanim 1988;13(1):3-18

[Free radicals and their significance for intensive care].

[Article in German]

Oppermann P, Rosolski T.

Publication Types: Review Review, tutorial

PMID: 3289560 [PubMed - indexed for MEDLINE]

1: Crit Care Clin 1988 Oct;4(4):645-60

Oxyradical species and their relationship to pathophysiology in pediatric critical care illness.

Zimmerman JJ.

Department of Pediatrics, University of Wisconsin, Madison.

Although energy metabolism is more efficient for the aerobic organism, oxyradical host autoinjury represents an attendant hazard. Generation of the toxic oxygen species is ubiquitous in an oxygen environment. Although several inducible enzyme systems have evolved to detoxify these various oxygen species, proteins, lipids, and nucleic acids remain at particular risk for oxyradical sabotage. Many critical care illnesses involve oxyradical pathophysiology. Aside from supportive care, future intervention for these problems may involve manipulation of the oxyradical causality.

PMID: 3179776 [PubMed - indexed for MEDLINE]

1: J Leukoc Biol 1991 May;49(5):449-54

Respiratory burst capability of polymorphonuclear neutrophils and TNF-alpha serum levels in relationship to the development of septic syndrome in critically ill patients.

Trautinger F, Hammerle AF, Poschl G, Micksche M.

2nd Department of Dermatology, University of Vienna, Austria.

Activated polymorphonuclear neutrophils (PMN) and neutrophil activating mediators such as tumor necrosis factor-alpha (TNF-alpha) are thought to be involved in the pathophysiology of sepsis and multiple organ failure syndrome (MOFS). In critically ill patients at high risk for the development of septic syndrome (n = 17) peripheral blood PMN were assayed for O2- and H2O2 production after stimulation with phorbol myristate acetate (PMA, 40 nM). Serum TNF-alpha levels were determined by ELISA. At the time of admission to the intensive care unit we found significant higher levels of TNF-alpha (P = 0.0001) in the serum of patients finally developing sepsis correlating to higher respiratory burst capability in comparison to nonseptic patients. Additionally we were able to demonstrate a significant (P = 0.0016) lower dismutation rate of O2- to H2O2 in deceased patients in comparison to survivors. These results give further evidence that elevated levels of circulating TNF-alpha and activated PMN play a significant role in the pathogenesis of septic syndrome in critically ill patients.

PMID: 1849953 [PubMed - indexed for MEDLINE]

1: Arch Dis Child 1992 Apr;67(4 Spec No):388-92

Plasma hypoxanthine: a marker for hypoxic-ischaemic induced periventricular leucomalacia?

Russell GA, Jeffers G, Cooke RW.

Regional Neonatal Intensive Care Unit, Liverpool Maternity Hospital.

Cerebral ischaemia of the immature brain may result in cavitating periventricular leucomalacia (PVL), an important association of cerebral palsy. Hypoxanthine measured by high performance liquid chromatography was used as a marker of peripartum hypoxia and ischaemia in 116 infants at risk of PVL. PVL was detected by ultrasound. The 81 infants who were unaffected had median (range) gestation of 30 weeks (24-32), weight of 1336 g (724-3790), and a plasma hypoxanthine concentration of 7.8 mumol/l (2.4-48.9). The seven infants who had cavitating PVL had a median gestation of 28 weeks (26-30), weight of 1165 g (682-1860), and a hypoxanthine concentration of 31.9 mumol/l (7.1-149). Cavitating PVL was significantly dependent only on hypoxanthine when controlling for the effects of weight and gestation. This suggests that peripartum hypoxia-ischaemia may be one of the aetiological factors in cavitating PVL. Oxidation of hypoxanthine during reperfusion generates free radicals which may contribute to the tissue destruction of PVL. The association of hypoxia-ischaemia with PVL suggests that PVL may be modified by reducing free radical activity.

PMID: 1586176 [PubMed - indexed for MEDLINE]

1: Dimens Crit Care Nurs 1994 Sep-Oct;13(5):256-62

Oxygen radicals and calcium ion flux: role in reperfusion injury following AMI.

Sharber J.

Occlusion of coronary vessels is now frequently treated by reperfusion using thrombolytics, angioplasty, or coronary artery bypass surgery. On reperfusion, however, acutely ischemic cells may be damaged by the action of oxygen radicals on cell membranes, and by calcium ion flux. By understanding the mechanisms behind reperfusion injury, the critical care nurse can assess and plan for actual and potential patient care problems.

PMID: 7988339 [PubMed - indexed for MEDLINE]

1: Ann Acad Med Singapore 1994 Nov;23(6 Suppl):40-8

Free radicals in anaesthesia and intensive care.

Tew DN, Jones JG.

Department of Anaesthesia, Addenbrooke's Hospital, Cambridge, United Kingdom.

This review aims to outline the nature and origin of free radicals, or oxidants, in biological systems and to summarise their involvement in diseases of interest to anaesthetists, with particular reference to reperfusion injury (of the gut, brain, myocardium and transplanted organs), shock/trauma, inflammation/sepsis and halothane hepatitis. In-vitro and animal studies examining the role of free radicals and antioxidants in the pathophysiology and treatment of these conditions are presented. Some of the evidence from clinical studies supporting the use of antioxidant therapy in patients is also presented.

Publication Types: Review Review, tutorial

PMID: 7710236 [PubMed - indexed for MEDLINE]

1: Intensive Crit Care Nurs 1995 Dec;11(6):336-40

Oxygen free radicals: in search of a unifying theory of disease.

Parkinson D.

The purpose of this paper is to examine the subject of oxygen free radicals and the damage they do in the human body, providing understanding of the basic principles involved, while at the same time highlighting areas of debate relevant to nurses working in critical care areas. Links to various areas of disease are explored, including coronary artery disease, cancer and reperfusion injuries. Ageing is also discussed. The role of antioxidant therapy is examined, as is the need for further research of the subject in general.

Publication Types: Review Review, tutorial

PMID: 8574085 [PubMed - indexed for MEDLINE]

1: Anesteziol Reanimatol 1996 May-Jun;(3):40-3

[The intensive therapy of posthypoxic encephalopathy].

[Article in Russian]

Shchukovskii VV, Aleksandrovich LM, Borisov AI, Khazov BE, Belov OV, Fisun AM.

A complex of therapeutic measures including hyperbaric oxygenation combined with heparin and endolumbal injection of glucocorticoids, proteolysis inhibitors, was carried out in 49 patients aged 16 to 95 with posthypoxic encephalopathy caused by mechanical asphyxia (11 patients,) carbon monoxide (12 cases), narcotics (18 cases), and closed craniocerebral injury (8 patients). Lipid peroxidation, some parameters of homeostasis, electrolyte, acid-base, and gaseous composition of the blood and liquor were studied before and during treatment. Positive clinical results were attained in 88.6% cases. Multiple-modality treatment of this patient population led to normalization of the coagulation potential of the blood and of the content of fibrinogen, but did not appreciably affect the electrolyte balance, acid-base, and gaseous composition of the blood. The activity of superoxide dismutase normalized, but the concentration of malonic dialdehyde increased, with the levels of dienic conjugates and nonerythrocytic hemoglobin being unchanged; however, the metabolic acidosis in the liquor still persisted.

PMID: 8967618 [PubMed - indexed for MEDLINE]

1: Anesteziol Reanimatol 1996 Nov-Dec;(6):56-8

[Effects of hyperbaric oxygenation on free radical oxidation and antioxidant system of blood in the newborn who had acute hypoxia at birth].

[Article in Russian]

Baiborodov BD, Savel'eva TV, Prokopenko VM, Evsiukova II, Arutiunian AV.

Hyperbaric oxygenation (HBO) was added to the complex of intensive care for 14 full-term newborns born asphyxiated and with cerebral circulation disorders of the I-II degree. Study of the antioxidant enzymatic system and free-radical oxidation by chemiluminescence showed no changes in superoxide dismutase and catalase and a 1.6-2 times increase in the activity of glutathione peroxidase, on the one hand, and an appreciable decrease of free radical processes, on the other. This permitted a conclusion about the absence of toxic effects during HBO and on its membrane-stabilizing action.

PMID: 9045586 [PubMed - indexed for MEDLINE]

1: Crit Care Med 1997 Jan;25(1):78-84

Skeletal muscle glutathione is depleted in critically ill patients.

Hammarqvist F, Luo JL, Cotgreave IA, Andersson K, Wernerman J.

Department of Surgery, St. Goran's Hospital, Stockholm, Sweden.

OBJECTIVE: To investigate the concentrations of reduced and total glutathione in relation to the muscle free amino acid pattern in critically ill patients and matched healthy controls. DESIGN: Prospective case control. SETTING: University hospital intensive care unit (ICU). PATIENTS: Eleven critically ill patients in the intensive care unit were studied after a stay of at least 4 days. Eleven age- and gender-matched metabolically healthy patients undergoing elective surgical procedures served as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Reduced and total glutathione concentrations were determined in skeletal muscle, in plasma, and in whole blood, together with muscle free amino acid concentrations. In the ICU group, reduced and total glutathione values were 57% and 62%, respectively, of the values seen in the control group (p < .001). In addition, a decreased ratio between reduced and total glutathione compared with the controls was seen (0.80 as compared with 0.91, p < .001). The glutamine concentration in skeletal muscle in the ICU group was 72% lower compared with that value seen in healthy controls (p < .001). Correlations were found between the concentrations of glutamine and the total muscle glutathione (r2 = .46, p < .001), as well as between glutamine and the ratio of reduced and total glutathione (r2 = .45, p < .001) in skeletal muscle, suggesting that the redox status of glutathione and the glutamine status of the tissue are related. CONCLUSIONS: Critical illness is associated with alterations in muscle glutathione metabolism. The muscle-reduced glutathione concentrations decrease and, in addition, the ratio between reduced and total glutathione decreases, indicating a situation of oxidative stress in this tissue. This decrease may impair the defense of muscle against oxygen free radicals and influence amino acid transport, thus contributing to the loss of balance between protein synthesis and protein degradation that is characteristic of protein catabolism.

PMID: 8989180 [PubMed - indexed for MEDLINE]

1: Cell Mol Neurobiol 1999 Feb;19(1):3-17

Application of a novel technique for clinical evaluation of nitric oxide-induced free radical reactions in ICU patients.

Hayashi N, Utagawa A, Kinoshita K, Izumi T.

Nihon University Critical and Emergency Care Center, Tokyo, Japan.

1. We recently developed a new technique for measuring serum NO2 and NO3 levels precisely, and we examined these parameters in severely brain-injured ICU patients who could not take nutrition intestinally. 2. Our results demonstrated that NO increased rapidly after stroke, trauma, and the occurrence of infection in all ICU patients. Elevation of NO2/NO3 was most pronounced 24 to 48 hr after trauma or ischemic stroke. This dysregulation of free radical elimination closely correlated with hemoglobin levels. 3. In most ICU patients, with the exception of those with complications of infection, the free radical potentials were maximal at 24 to 48 hr and continued to remain high for 4 to 5 days after trauma or stroke. The level of free radical potentials was closely correlated with the severity and prognosis of critically injured patients. None with radical potential values higher than 0.4 microM survived. 4. Clinically, the maintenance of hemoglobin at > 12 g/dl and lower body temperature were demonstrated to be successful in the management of these free radical reactions.

PMID: 10079961 [PubMed - indexed for MEDLINE]

1: Am J Respir Crit Care Med 2000 Jun;161(6):1907-11

The effect of glutathione and N-acetylcysteine on lipoperoxidative damage in patients with early septic shock.

Ortolani O, Conti A, De Gaudio AR, Moraldi E, Cantini Q, Novelli G.

Department of Anesthesiology and Intensive Care, University of Florence, Italy.

Both the hyperproduction of oxygen free radicals (OFR) and the weakening of natural scavenging mechanisms have been implicated as contributors to multiple organ failure in septic shock. This study examined whether the antioxidants glutathione (GSH) and N-acetyl-L-cysteine (NAC) play a protective role against damage by OFR in early septic shock. We randomly entered 30 patients with septic shock into one of three groups within 24 h of diagnosis. All of the patients received septic shock therapy, including parenteral nutrition, antibiotics, and volume-expanding and inotropic agents. One group (Group B) also received 70 mg/kg/d of intravenous GSH, and a second group (Group C), 70 mg/kg/d of intravenous GSH and 75 mg/kg/d of intravenous NAC. The protection against OFR damage was evaluated by measuring expired ethane, plasma malondialdehyde, erythrocyte deformability, complement activation, and clinical scores at admission and on Days 3 and 5 of treatment. A significant decrease in peroxidative indexes was observed at Day 5 in Group B as compared with both the control group and basal values. The decrease in peroxidative indexes was even more marked in Group C. Clinical scores in this group were also significantly improved. In conclusion, the administration of high doses of NAC added to GSH significantly decreased the peroxidative stress of patients with septic shock.

Publication Types: Clinical trial Randomized controlled trial

PMID: 10852765 [PubMed - indexed for MEDLINE]

1: Vestn Khir Im I I Grek 2000;159(3):37-9

[Solcoseryl in intensive therapy in severe craniocerebral trauma].

[Article in Russian]

Marusanov VE, Miroshnichenko AG, Nikolau SA, Petrova NV, Bichun AB.

The state of processes of lipid peroxidation and antioxidant defense was studied in patients with severe isolated craniocerebral closed injury. It was found that starting from the first days in the hospital the patients demonstrated marked alterations in the thiol-disulfide and ascorbate metabolism, activation of lipid peroxidation processes and lower antioxidant defense. The use of Solcoseryl as a component of the antioxidant therapy in treatment of the above mentioned category of patients resulted in considerably better indices of the thiol-disulfide metabolism. The isolated use of Solcoseryl failed to influence the ascorbate metabolism and lipid peroxidation. Solcoseryl used in combination with the ascorbic acid led to normalization of the thiol-disulfide and ascorbade metabolism without influencing the lipid peroxidation processes. Combined use of Solcoseryl and ascorbic acid promoted normalization of the neurological status and stabilization of the arterial pressure level.

Publication Types: Clinical trial

PMID: 10983337 [PubMed - indexed for MEDLINE]

1: Crit Care 2000;4(5):290-6

Critical advances in septicemia and septic shock.

Das UN.

EFA Sciences LLC, Norwood, Massachusetts 02062, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

Recent advances suggest that toll-like receptors, various cytokines, cicosanoids, free radicals and macrophage migration inhibitory factor (MIF) play an important role in the pathobiology of septicemia and septic shock. Anti-MIF antibodies can decrease the plasma concentrations of tumor necrosis factor (TNF), lower bacterial circulating counts and enhance survival of animals with septicemia and septic shock. Monocyte expression of MHC-class II antigens, neutrophil expression of the integrin CD11b/CD18 and neutrophil activation can be related to the development of, and/or recovery from, post-operative sepsis. Thus, biological variations in the response of an individual to a given stimulus, appears to determine his/her ability or inability to develop and also recover from sepsis and septic shock. This suggests that it may be possible to predict the development of septicemia and septic shock in a given individual and take appropriate action both to prevent and treat them adequately.

Publication Types: Review Review, tutorial

PMID: 11094508 [PubMed - indexed for MEDLINE]

1: J Cardiovasc Surg (Torino) 1999 Feb;40(1):65-9

Plasma hypoxanthine levels during crystalloid and blood cardioplegias: warm blood cardioplegia increases hypoxanthine levels with a greater risk of oxidative stress.

Quinlan GJ, Westerman ST, Mumby S, Pepper JR, Gutteridge JM.

Department of Anaesthesia and Adult Intensive Care, Royal Brompton Hospital, National Heart and Lung Institute, Imperial College of Science Technology and Medicine, London, UK.

BACKGROUND: Patients undergoing cardiopulmonary bypass (CPB) are subjected to severe oxidative stress, and frequently show evidence of acute lung injury post surgery. Associations between acute lung injury, oxidative stress, and aberrant ATP catabolism have been made and prompted us to consider whether the purine metabolites xanthine and hypoxanthine alter significantly during CPB when different types of cardioplegia are used. METHODS: Experimental design: retrospective follow up study on stored plasma samples from patients randomly selected to receive either warm blood, cold blood, or crystalloid cardioplegia. Setting: adult intensive care unit of post graduate teaching hospital. Patients: thirty-eight patients undergoing aortic valve replacement, with or without artery grafting. Operation was carried out by a single surgeon. Interventions: all patients received either a homograft aortic valve or a stentless porcine valve. RESULTS: No significant differences in xanthine levels at any time points during CPB, or between the different cardioplegic groups. Hypoxanthine levels were, however, significantly higher in patients receiving warm blood cardioplegia (74.84+/-16.715 microM, p=0.0151), and was most marked at time point 3 when the aortic cross clamp was released. Patients receiving crystalloid cardioplegia showed higher levels of hypoxanthine (44.56+/-10.16 microM) than those receiving cold blood cardioplegia (21.57+/-7.106 microM). CONCLUSIONS: Considering these data together, it suggests that aberrant ATP catabolism, characteristic of ischaemia/reperfusion, is further disturbed during warm blood cardioplegia leading to a marked increase in plasma hypoxanthine levels. This has the potential to further increase oxidative stress during CPB.

PMID: 10221389 [PubMed - indexed for MEDLINE]

1: Intensive Care Med 1999 Feb;25(2):180-5

Comment in: Intensive Care Med. 1999 Feb;25(2):134-6

Antioxidant status in patients with acute respiratory distress syndrome.

Metnitz PG, Bartens C, Fischer M, Fridrich P, Steltzer H, Druml W.

Dept. of Anesthesia and General Intensive Care, Vienna General Hospital, University of Vienna, Austria.

OBJECTIVES: Reactive oxygen species (ROS) have been implicated in the pathophysiology of ARDS. We investigated the pattern of antioxidants in plasma and ROS production by neutrophils in patients with ARDS over 6 days. DESIGN: Observational study. Blood samples were taken when the diagnosis was made (D0) and after 3 (D3) and 6 days (D6) during therapy. SETTING: Intensive care units at a University Hospital. PATIENTS: Eight patients with ARDS were investigated, 17 healthy volunteers served as controls. MEASUREMENTS AND RESULTS: Plasma levels of ascorbate, alpha-tocopherol, retinol, beta-carotene, selenium and lipid peroxidation products (MDA) were determined and the activities of the antioxidative enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione-peroxidase (GSH-PX) in erythrocytes were measured. In addition, ROS production (superoxide anion and hydrogen peroxide) in activated neutrophils was assessed. Plasma levels of alpha-tocopherol, ascorbate, beta-carotene and selenium were reduced from the onset of illness. MDA plasma levels were increased throughout the illness. ROS generation from neutrophils was normal on D0 and decreased to D6 in ARDS patients. CONCLUSION: The antioxidative system is severely compromised in patients with ARDS. Plasma levels of alpha-tocopherol, ascorbate, beta-carotene and selenium are decreased. Elevated MDA levels provide further evidence of massive oxidative stress. The routine replacement of micronutrients according to recommended daily allowances was inadequate to compensate for the increased requirements.

PMID: 10193545 [PubMed - indexed for MEDLINE]

1: Med Klin 1999 Oct 15;94 Suppl 3:54-7

[Significance of selenium in intensive care medicine. Clinical studies of patients with SIRS/sepsis syndrome].

[Article in German]

Gartner R, Angstwurm M.

Medizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians-Universitat Munchen. This email address is being protected from spambots. You need JavaScript enabled to view it.

Selenium is an essential component of the intracellular antioxidant system as a structural component of the active center of the glutathione peroxidase enzymes. These selenoenzymes play a major role in protecting cells against peroxidation, especially lipid peroxidation and selenium seems to play a direct role in the regulation of inflammatory processes. In conditions of systemic inflammatory response or sepsis, patients are exposed to severe oxidative stress. These patients already have both, a decreased plasma selenium and glutathione peroxidase activity at admission to the ICU as has been shown in several studies. The degree of selenium deficiency is correlated with the severity of disease and the incidence of mortality. The reason for the low plasma selenium levels is unknown. Especially it would be of interest a) if the low plasma selenium is the consequence of the systemic inflammatory response with distribution of selenium in other compartments of the body, b) most important, whether the substitution of selenium might improve the outcome and decrease the mortality rate of these patients. In 2 independently performed intention-to-treat studies including patients with systemic inflammatory response syndrome or sepsis a beneficial effect of selenium supplementation on multiple organ function and outcome could already be demonstrated as well as a tendency of an improved mortality rate. A prospective analytical study clearly could demonstrate the inverse relationship between low plasma selenium and morbidity and mortality of patients with SIRS/sepsis. The results of these studies are so convincing, that we propose a randomized, prospective, double blind multicenter phase-III study including patients with systemic inflammatory response syndrome or sepsis to investigate, whether a high-dose selenium substitution in addition to the recommended treatment strategies for patients with sepsis improves outcome and mortality rate of these patients.

Publication Types: Review Review, tutorial

PMID: 10554531 [PubMed - indexed for MEDLINE]

1: Med Klin 1999 Oct 15;94 Suppl 3:54-7

[Significance of selenium in intensive care medicine. Clinical studies of patients with SIRS/sepsis syndrome].

[Article in German]

Gartner R, Angstwurm M.

Medizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians-Universitat Munchen. This email address is being protected from spambots. You need JavaScript enabled to view it.

Selenium is an essential component of the intracellular antioxidant system as a structural component of the active center of the glutathione peroxidase enzymes. These selenoenzymes play a major role in protecting cells against peroxidation, especially lipid peroxidation and selenium seems to play a direct role in the regulation of inflammatory processes. In conditions of systemic inflammatory response or sepsis, patients are exposed to severe oxidative stress. These patients already have both, a decreased plasma selenium and glutathione peroxidase activity at admission to the ICU as has been shown in several studies. The degree of selenium deficiency is correlated with the severity of disease and the incidence of mortality. The reason for the low plasma selenium levels is unknown. Especially it would be of interest a) if the low plasma selenium is the consequence of the systemic inflammatory response with distribution of selenium in other compartments of the body, b) most important, whether the substitution of selenium might improve the outcome and decrease the mortality rate of these patients. In 2 independently performed intention-to-treat studies including patients with systemic inflammatory response syndrome or sepsis a beneficial effect of selenium supplementation on multiple organ function and outcome could already be demonstrated as well as a tendency of an improved mortality rate. A prospective analytical study clearly could demonstrate the inverse relationship between low plasma selenium and morbidity and mortality of patients with SIRS/sepsis. The results of these studies are so convincing, that we propose a randomized, prospective, double blind multicenter phase-III study including patients with systemic inflammatory response syndrome or sepsis to investigate, whether a high-dose selenium substitution in addition to the recommended treatment strategies for patients with sepsis improves outcome and mortality rate of these patients.

Publication Types: Review Review, tutorial

PMID: 10554531 [PubMed - indexed for MEDLINE]

1: Br Med Bull 1999;55(1):49-75

Redox imbalance in the critically ill.

Gutteridge JM, Mitchell J.

Oxygen Chemistry Laboratory, Royal Brompton and Harefield NHS Trust, London, UK.

The majority of deaths amongst critically ill patients requiring intensive care are attributable to sepsis and its sequelae: septic shock, the systemic inflammatory response syndrome (SIRS) and the acute respiratory distress syndrome (ARDS). Clinically, sepsis/SIRS and ARDS are characterised by disordered vascular control, manifest as systemic hypotension and peripheral vasodilation refractory to intravascular volume resuscitation and vasopressor therapy; and pulmonary hypertension. Experimental and clinical evidence demonstrates that these patients suffer from severe oxidative stress. Thus, our own and other groups have shown that the vascular pathology of sepsis/SIRS and ARDS is initiated through the uncontrolled production of reactive oxygen (ROS) and reactive nitrogen species (RNS) which modulate inflammatory cell adhesion and cause direct injury to endothelium (Fig. 1).

Publication Types: Review Review, academic

PMID: 10695079 [PubMed - indexed for MEDLINE]

1: Crit Care Med 2000 Dec;28(12):3828-32

Enteral feeding with a solution enriched with antioxidant vitamins A, C, and E enhances the resistance to oxidative stress.

Preiser JC, Van Gossum A, Berre J, Vincent JL, Carpentier Y.

Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium. This email address is being protected from spambots. You need JavaScript enabled to view it.

OBJECTIVE: To assess whether dietary supplementation with the antioxidant vitamins A, C, and E enhances parameters of oxidative stress and influences the course of critically ill patients. DESIGN: Prospective, randomized, double-blinded, placebo-controlled study. SETTING: Department of medicosurgical intensive care of an academic hospital. PATIENTS: Fifty-one patients expected to require at least 7 days of enteral feeding. Thirty-seven of these patients (age, 57 +/- 7 yrs; Simplified Acute Physiology Score II, 33 +/- 6 points) completed the study. INTERVENTIONS: Twenty patients were randomized to receive the formula supplemented with vitamins A (67 microg/dL), C (13.3 mg/ dL), and E (4.94 mg/dL), and 17 patients received an isocaloric and isonitrogenous control solution. MEASUREMENTS AND MAIN RESULTS: Plasma levels of antioxidant vitamins, lipid peroxidation (estimated by the malonyldialdehyde assay), and low-density lipoprotein (LDL), and erythrocyte resistance to experimental oxidative stress were determined on samples drawn two consecutive days before the initiation of feeding and at the end of the 7-day period. Clinical outcome measures included documented infection and intensive care unit and 28-day survival. Administration of the supplemented solution increased significantly the concentration of plasma beta-carotene (from 0.2 +/- 0.0 microg/mL to 0.6 +/- 0.1 microg/mL; p < 0.01) and plasma and LDL-bound alpha-tocopherol (from 6.0 +/- 0.4 microg/mL and 2.9 +/- 0.9 microg/mL to 9.7 +/- 0.5 microg/mL and 4.3 +/- 1.2 microg/mL, respectively; p < 0.05), and improved LDL resistance to oxidative stress by 21 +/- 4% (p < 0.05). No such change was observed in the control group. There was no significant difference in clinical outcome between the two groups. CONCLUSIONS: Supplemental antioxidant vitamins added to enteral feeding solutions are well absorbed. Dietary supplementation with vitamins A, C, and E is associated with an improvement in antioxidant defenses, as assessed by ex vivo tests.

Publication Types: Clinical trial Randomized controlled trial

PMID: 11153621 [PubMed - indexed for MEDLINE]

1: Panminerva Med 2001 Mar;43(1):27-31

Oxidative stress status: possible guideline for clinical management of critically ill patients.

Bela P, Bahl R, Sane AS, Sawant PH, Shah VR, Mishra VV, Trivedi HL.

Departments of Biochemistry, Anaesthesiology, Institute of Kidney Disease and Research Centre Ahmedabad, India.

BACKGROUND: Critical care medicine has developed in the last few years into a separate scientific discipline and studies related to the outcome after intensive care usually suggest a long hospital stay that becomes cost prohibitive. The majority of problems (death) amongst critically ill patients requiring critical care involve sepsis, inflammation, tissue damage-oxidative stress, oxygen tension PO2, lipid peroxidation. The present investigation involves monitoring of serum levels of MDA, SOD as a possible guideline for severity of clinical situations in critically ill patients. METHODS: Fifty critically ill heterogeneous patients requiring intensive care in the ICU of IKDRC were selected as subjects with ages varying from 17 to 75 years. Serum levels of MDA (ng/ml), SOD (U/ml) were determined right from admission to discharge due to improvement / DAMA / death. MDA and SOD were estimated according to the methods of Buege and Aust et al. (1978), Nandi and Chatterji (1988). RESULTS: Critically ill patients irrespective of the disease process indicated significantly very high serum levels of MDA and low levels of SOD at the time of admission (13.28+/-4.26 ng/ml, 3.80+/-2.60 U/ml, respectively) according to the severity of the prevalent clinical situation. The pattern of serum levels of MDA and SOD according to subsequent clinical performance did indicate a decreasing trend of MDA (oxidant) and fluctuating trend of SOD (antioxidant enzyme except in those who inevitably succumbed to death in spite of adequate clinical management. CONCLUSIONS: The results of the present study have amply revealed the utility and relevance of monitoring oxidative stress in critically ill patients as biochemical markers, cost-effectiveness and role in decision making (withdrawal/continuation of different support modalities) as deemed fit.

PMID: 11319515 [PubMed - indexed for MEDLINE]

1: Intensive Care Med 2001 Jan;27(1):216-21

Xanthine oxidase activity and blood glutathione redox ratio in infants and children with septic shock syndrome.

Nemeth I, Boda D.

Department of Pediatrics, Medical Faculty of Szeged University, Hungary.

OBJECTIVES: The possible role of xanthine oxidase (XO) activation in the signal transduction process during the septic shock syndrome was examined. The XO activity index after caffeine intake was assessed simultaneously with the blood glutathione redox ratio, a known parameter of oxidative stress. DESIGN AND SETTING: An investigational clinical study in a nine-bed pediatric intensive care unit. PATIENTS: Critically ill infants and children (n = 34) with systemic inflammatory response syndrome following infection, trauma or major surgery. Biochemical investigations (n = 54) were performed at various stages of the shock syndrome, characterized by pediatric risk of mortality and organ dysmetabolic scores. Controls consisted of 30 healthy children. MEASUREMENTS AND RESULTS: The in vivo XO activity index was measured as the urinary ratio of two metabolites of caffeine: 1-methyluric acid and 1-methylxanthine. The blood concentrations of oxidized (GSSG) and reduced glutathione (GSH) were determined. The XO activity index and redox ratio GSSG/GSH were highly increased in patients in shock dominated by the clinical symptoms of a proinflammatory response. A significantly lower XO activity index was found with an increased GSSG/ GSH in patients whose stage of shock was characteristic of an excessive anti-inflammatory response. The XO activity index and GSSG/ GSH were correlated closely with each other (r = 0.624, n = 54; p < 0.001), and were also related to the daily severity scores. CONCLUSION: Potent and simultaneous activation of the two redox systems strongly indicates a definite role of free radicals from XO in the overspill of the acute proinflammatory reaction of the shock syndrome, followed by a significant downregulation.

PMID: 11280638 [PubMed - indexed for MEDLINE]