Organ Dysfunction In Shock Research Articles

A pilot study of exercise-induced changes in mitochondrial oxygen metabolism measured by a cellular oxygen metabolism monitor (PICOMET)

Impaired tissue oxygenation is the key pathomechanism in the development of organ dysfunction in shock; mitochondrial impairment can aggravate the condition. However, measuring tissue oxygenation directly and non-invasively still poses a clinical challenge. A novel device (COMET) allows the assessment of mitochondrial oxygen metabolism using the Protoporphyrin IX Triplet State Lifetime Technique (PpIX-TSLT). Critically ill patients, especially in sepsis, often exhibit oedema which may interfere with the COMET measurement. Furthermore, patients' physical activity level differs significantly before and during hospitalisation. Thus, the aim of this study was to identify the effects of physical activity and body composition on mitochondrial oxygen tension (mitoPO2) and consumption (mitoVO2) in healthy controls (N = 40). Furthermore, the study tested the repeatability of the COMET variables and identified covariates. Multiple COMET measurements were performed before (T1, T2), during and after (T3, T4) ergometry. Body composition was assessed by bioimpedance analysis. Physiological variables (blood pressure, heart rate, oxygen saturation) were recorded. In the analytical sample (n = 26), physical activity significantly decreased mitoVO2; other COMET variables remained unchanged between T2 and T3. During ergometry, mitoPO2 increased significantly. The distribution of body water significantly influenced mitoVO2. In our setting, the method demonstrated moderate repeatability. Variables of fitness (heart rate recovery, phase angle and physical activity level), signal quality and duration of exposure to 5-aminolevulinic acid (obligatory for PpIX-TSLT) were identified as significant covariates of mitoVO2. Mitochondrial oxygen delivery (mitoDO2) was established as a new variable of COMET analysis. Results of this pilot study should be validated in future studies.

Association between hyperglycemia and organ dysfunction in shock patients

Background Hyperglycemia is an important marker of bothpoor clinical outcomes and high mortality rate in critically illpatients. Glucose toxicity results in cell damage that leads toorgan dysfunction.Objective To evaluate for an association between hyperglycemiaand the incidence of organ dysfunction in shock patients.Methods This cross-sectional study was conducted in thepediatric intensive care unit (PICU) of Dr. Moh. HoesinHospital, Palembang from June to November 2011. Subjectswere consecutively-enrolled, shock patients without a historyof diabetes mellitus. Illness severity and organ dysfunction weredetermined by pediatric risk of mortality (PRISM) III score andpediatric logistic organ dysfunction (PELOD) scores, respectively.Hyperglycemia was defined as a blood glucose level 2: 110 mg/dL.Statistical analysis was performed with SPSS version 15.Results Mean age of subjects was 2.30 (SD 2.93) years. MeanPRISM III score was 15 .11 (SD 5 .63). Prevalence of hyperglycemiawas 80.0%. Mean glucose level was 179.51 (SD 86.84) mgldL.Mean PELOD score was 16.02 (SD 13.87). Organ dysfunction wasobserved in 86.7% of subjects. The most common organ dysfunctionobserved in our subjects was liver dysfunction (73.3%). Therewas a significant association between hyperglycemia and organdysfunction (OR43.750;95%CI 4.036 to474.252, P=0.001). Theblood glucose level cutoff points indicative of organ dysfunction,PRISM III score 2: 8, and PELOD score 2: 20.5 were 114.5 mg/dL, 129 mgldL, and 166 mg/dL, respectively.Conclusion There is an association between hyperglycemia andorgan dysfunction. The upper limit blood glucose level indicative oforgan dysfunction is 114.5 mg/dL. A glucose level of 129 mgldL maybe considered to be a warning to start blood glucose monitoring. Alevel above 166 mgldL may be used to indicate the necessity of startinginsulin therapy intervention.

The Pancreas as a Source of Cardiovascular Cell Activating Factors

Physiological shock leads to elevated levels of plasma factors that activate circulating leukocytes and endothelial cells, thereby compromising microvascular functions. The nature and source of these plasma-derived activators are unknown. To examine the possible origin of these factors, we homogenized rat internal organs and measured their activity on cardiovascular cells in vivo and in vitro. Fresh tissue samples from small intestine, spleen, heart, liver, kidney, adrenals, and pancreas were homogenized. Their ability to induce leukocyte pseudopod formation and nitroblue tetrazolium (NBT) reduction was tested and their impact in vivo on blood pressure, survival, and microvascular cell injury was examined. A dramatic increase (p < 0.001) in leukocyte activation compared to controls was observed with pancreas homogenate but not with homogenates from the other organs. Leukocyte activation was induced by homogenates of other tissues only after prior incubation with substimulatory concentrations of pancreatic homogenate. Pancreatic serine proteases, trypsin and chymotrypsin, which did not stimulate leukocytes, also generated activity from other tissues. Leukocyte pseudopod formation could be significantly inhibited by adding the serine protease inhibitor 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate (ANGD) during tissue homogenization (p < 0.001). Injection of pancreatic homogenate into rats led to increased plasma hydrogen peroxide levels and an instantaneous drop in mean arterial pressure that was often lethal. These responses were prevented by prior infusion of ANGD (p < 0.001). Intravital microscopy of the rat mesentery confirmed that superfusion of filtered pancreatic homogenate leads to significant increases in cell death (p < 0.05), as detected by propidium iodide, and hydrogen peroxide formation (p < 0.05), as determined by dichlorofluorescein diacetate (DCFH) fluorescence. These results suggest that pancreatic enzymes attack tissue and generate cellular activators that are associated with organ dysfunction in shock.