EEG power as a biomarker to predict the outcome after cardiac arrest and cardiopulmonary resuscitation induced global ischemia.

AIMS: Cardiac arrest (CA) is a major cause of mortality and survivors often develop neurologic deficits. The objective of this study was to determine the effect of CA and cardiopulmonary resuscitation (CPR) in mice on the EEG and neurologic outcomes, and identify biomarkers that can prognosticate poor outcomes. MAIN METHODS: Video-EEG records were obtained at various periods following CA-CPR and examined manually to determine the presence of spikes and sharp-waves, and seizures. EEG power was calculated using a fast Fourier transform (FFT) algorithm. KEY FINDINGS: Fifty percent mice died within 72h following CA and successful CPR. Universal suppression of the background EEG was observed in all mice following CA-CPR, however, a more severe and sustained reduction in EEG power occurred in the mice that did not survive beyond 72h than those that survived until sacrificed. Spikes and sharp wave activity appeared in the cortex and hippocampus of all mice, but only one out of eight mice developed a purely electrographic seizure in the acute period after CA-CPR. Interestingly, none of the mice that died experienced any acute seizures. At 10days after the CA-CPR, 25% of the mice developed spontaneous convulsive and nonconvulsive seizures that remained restricted to the hippocampus. The frequency of nonconvulsive seizures was higher than that of convulsive seizures. SIGNIFICANCE: A strong association between changes in EEG power and mortality following CA-CPR were observed in our study. Therefore, we suggest that the EEG power can be used to prognosticate mortality following CA-CPR induced global ischemia.

Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis.

INTRODUCTION: Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized that injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade; however, outcome data in experimental models have been contradictory. Thus, we investigated the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP) model of sepsis. METHODS: Sprague-Dawley rats receiving either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or control (normal saline), underwent CLP and were monitored for survival. Additionally, lung and blood samples were collected at 6 and 24 hours for analysis. Animals also underwent monitoring to evaluate global hemodynamics. RESULTS: Seven days following CLP, propranolol improved survival versus control (P < 0.01). Heart rates in the propranolol-treated rats were approximately 23% lower than control rats (P < 0.05) over the first 24 hours, but the mean arterial blood pressure was not different between groups. Metabolic analysis of lung tissue demonstrated an increase in lung ATP/ADP ratio and NAD+ content and a decreased ratio of polyunsaturated fatty acids to monounsaturated fatty acids (PUFA/MUFA). Cytokine analysis of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) demonstrated decreased expression of TNF-alpha in both lung and plasma at 24 hours post CLP induced sepsis. Finally, propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression was unchanged. CONCLUSIONS: These results suggest that propranolol treatment may decrease mortality during sepsis potentially via a combination of improving metabolism, suppressing aspects of the inflammatory response and enhancing tissue protection.

Left ventricular assist device effects on metabolic substrates in the failing heart.

BACKGROUND: Heart failure patients have inadequate nutritional intake and alterations in metabolism contributing to an overall energy depleted state. Left ventricular assist device (LVAD) support is a common and successful intervention in patients with end-stage heart failure. LVAD support leads to alterations in cardiac output, functional status, neurohormonal activity and transcriptional profiles but the effects of LVADs on myocardial metabolism are unknown. This study set out to measure cardiac metabolites in non-failing hearts, failing hearts, and hearts post-LVAD support. METHODS: The study population consisted of 8 non-ischemic failing (at LVAD implant) and 8 post-LVAD hearts, plus 8 non-failing hearts obtained from the tissue bank at the University of Colorado. NMR spectroscopy was utilized to evaluate differences in myocardial energy substrates. Paired and non-paired t-tests were used to determine differences between the appropriate groups. RESULTS: Glucose and lactate values both decreased from non-failing to failing hearts and increased again significantly in the (paired) post-LVAD hearts. Glutamine, alanine, and aromatic amino acids decreased from non-failing to failing hearts and did not change significantly post-LVAD. Total creatine and succinate decreased from non-failing to failing hearts and did not change significantly post-LVAD. DISCUSSION: Measured metabolites related to glucose metabolism are diminished in failing hearts, but recovered their values post-LVAD. This differed from the amino acid levels, which decreased in heart failure but did not recover following LVAD. Creatine and the citric acid cycle intermediate succinate followed a similar pattern as the amino acid levels.

Characteristics and current practice of parenteral nutrition in hospitalized patients.

BACKGROUND: For 40 years, parenteral nutrition (PN) has provided therapeutic benefits to patients unable to receive oral/enteral nutrition. Very limited published evidence exists to describe modern PN practices or characteristics of patients receiving PN. The aim of this article was to describe the characteristics of hospitalized patients receiving PN in 196 U.S. hospitals to define patient groups at risk for PN-related complications. This will provide researchers a baseline understanding about who is receiving hospital-based PN to maximize generalizability and validity of future research. METHODS: Claims data from the Premier Perspective database, the largest inpatient clinical database in the United States, were used to evaluate hospital-based PN practices. Data gathered between January 2005 and December 2007 included a total of 106,374 patients receiving PN. A total of 68,984 adults (age ≥ 18 years), 34,307 infants (age <1 year), and 3083 pediatric patients (age 1-17 years) were evaluated. Key variables such as admitting diagnosis, infection rates, in-hospital mortality, and costs were extracted. RESULTS: Hospitalized patients requiring PN in the United States are older and more often white than the overall hospitalized population. Hospitalized PN patients are more likely to be admitted emergently and have a higher severity of illness. Bloodstream infection rates in adult PN patients (25.5%) were considerably higher than in pediatric (14.7%) or neonatal patients (1.7%) receiving PN. CONCLUSIONS: These findings are the first large-scale description of "real-world" hospital-based PN practices in the United States, helping set a baseline for future PN research.

Pharmacologically dosed oral glutamine reduces myocardial injury in patients undergoing cardiac surgery: a randomized pilot feasibility trial.

BACKGROUND AND OBJECTIVE: Glutamine (GLN) has been shown to protect against in vitro and in vivo myocardial injury. In humans, perioperative ischemia/reperfusion (I/R) injury during cardiac surgery is associated with higher morbidity and mortality. The objective of this safety and feasibility pilot trial was to determine if pharmacologically dosed, preoperative oral GLN attenuates myocardial injury in cardiac surgery patients. METHODS: Patients undergoing elective cardiac surgery, requiring cardiopulmonary bypass, were enrolled in a randomized, double-blind pilot trial to receive 25 g twice of oral alanyl-glutamine (GLN; n = 7) or maltodextrin (CONT; n = 7) daily for 3 days preoperatively. Serum troponin (TROP I), creatine kinase (CK-MB), and myoglobin (MG) were measured at multiple perioperative time points. Clinical outcomes were also recorded and assessed. RESULTS: GLN therapy significantly decreased TROP I levels at 24, 48, and 72 hours postoperatively (all P < .05) vs CONT. GLN also reduced CK-MB at 24 and 48 hours (P < .05, P < .001) vs CONT. MG was reduced at 24 hours vs control (P = .0397). GLN also significantly reduced pooled clinical complications vs CONT (P = .03). CONCLUSION: This pilot study showed that pharmacologically dosed oral GLN therapy prior to cardiac surgery was safe, well tolerated, and feasible. GLN therapy reduced myocardial injury and clinical complications in this small randomized, blinded feasibility trial. These data indicate that a larger trial of preoperative GLN therapy in patients undergoing cardiac surgery is needed to confirm clinical benefit.

Myocardial ischemia reperfusion injury: from basic science to clinical bedside.

Myocardial ischemia reperfusion injury contributes to adverse cardiovascular outcomes after myocardial ischemia, cardiac surgery or circulatory arrest. Primarily, no blood flow to the heart causes an imbalance between oxygen demand and supply, named ischemia (from the Greek isch, restriction; and haema, blood), resulting in damage or dysfunction of the cardiac tissue. Instinctively, early and fast restoration of blood flow has been established to be the treatment of choice to prevent further tissue injury. Indeed, the use of thrombolytic therapy or primary percutaneous coronary intervention is the most effective strategy for reducing the size of a myocardial infarct and improving the clinical outcome. Unfortunately, restoring blood flow to the ischemic myocardium, named reperfusion, can also induce injury. This phenomenon was therefore termed myocardial ischemia reperfusion injury. Subsequent studies in animal models of acute myocardial infarction suggest that myocardial ischemia reperfusion injury accounts for up to 50% of the final size of a myocardial infarct. Consequently, many researchers aim to understand the underlying molecular mechanism of myocardial ischemia reperfusion injury to find therapeutic strategies ultimately reducing the final infarct size. Despite the identification of numerous therapeutic strategies at the bench, many of them are just in the process of being translated to bedside. The current review discusses the most striking basic science findings made during the past decades that are currently under clinical evaluation, with the ultimate goal to treat patients who are suffering from myocardial ischemia reperfusion-associated tissue injury.

Physicians reentering clinical practice: characteristics and clinical abilities.

INTRODUCTION: Limited information exists to describe physicians who return to practice after absences from patient care. The Center for Personalized Education for Physicians (CPEP) is an independent, not-for-profit organization that provides clinical competency assessment and educational programs for physicians, including those reentering practice. This article studies the medical licensure status, performance, and correlates between physician characteristics and performance on initial assessment. METHODS: Sixty-two physicians who left practice voluntarily and without discipline or sanction and who were returning to practice in the same discipline as their previous practice participated in the CPEP reentry program. Physicians completed an objective clinical skills assessment including clinical interviews by specialty-matched board-certified physicians, simulated patient encounters, a documentation exercise, and a cognitive function screen. Physicians were rated from 1 (no or limited educational needs) to 4 (global, pervasive deficits). Performance scores were compared based on select physician characteristics. RESULTS: Twenty-five (40.3%) participants were female; participants' average age was 53.7 years (female 48.1 years; male 57.5 years). Physicians left practice for family issues (30.6%), health issues (27.4%), retirement or nonmedical career change (17.7%), and change to medical administration (14.5%). Females were more likely than males to have left practice for child rearing (P < 0.0001). Approximately one-quarter (24.2%) of participants achieved a performance rating of 1 (best-performing group); 35.5% achieved a rating of 2; 33% achieved a rating of 3; 6.5% achieved a rating of 4 (worst-performing group). Years out of practice and increasing physician age predicted poorer performance (P = 0.0403, P = 0.0440). A large proportion of physicians presenting without an active license achieved active licensure; how many of these physicians actually returned to practice is not known. DISCUSSION: Physicians who leave practice are a heterogeneous group. Most participants' performance warranted some formal education; few demonstrated global educational needs. The data from this study justify mandates that physicians demonstrate competence through an objective testing process prior to returning to practice. Emerging patterns regarding the performance of the reentering physician may help guide future policy.

Physicians reentering clinical practice: characteristics and clinical abilities.

INTRODUCTION: Limited information exists to describe physicians who return to practice after absences from patient care. The Center for Personalized Education for Physicians (CPEP) is an independent, not-for-profit organization that provides clinical competency assessment and educational programs for physicians, including those reentering practice. This article studies the medical licensure status, performance, and correlates between physician characteristics and performance on initial assessment. METHODS: Sixty-two physicians who left practice voluntarily and without discipline or sanction and who were returning to practice in the same discipline as their previous practice participated in the CPEP reentry program. Physicians completed an objective clinical skills assessment including clinical interviews by specialty-matched board-certified physicians, simulated patient encounters, a documentation exercise, and a cognitive function screen. Physicians were rated from 1 (no or limited educational needs) to 4 (global, pervasive deficits). Performance scores were compared based on select physician characteristics. RESULTS: Twenty-five (40.3%) participants were female; participants' average age was 53.7 years (female 48.1 years; male 57.5 years). Physicians left practice for family issues (30.6%), health issues (27.4%), retirement or nonmedical career change (17.7%), and change to medical administration (14.5%). Females were more likely than males to have left practice for child rearing (P < 0.0001). Approximately one-quarter (24.2%) of participants achieved a performance rating of 1 (best-performing group); 35.5% achieved a rating of 2; 33% achieved a rating of 3; 6.5% achieved a rating of 4 (worst-performing group). Years out of practice and increasing physician age predicted poorer performance (P = 0.0403, P = 0.0440). A large proportion of physicians presenting without an active license achieved active licensure; how many of these physicians actually returned to practice is not known. DISCUSSION: Physicians who leave practice are a heterogeneous group. Most participants' performance warranted some formal education; few demonstrated global educational needs. The data from this study justify mandates that physicians demonstrate competence through an objective testing process prior to returning to practice. Emerging patterns regarding the performance of the reentering physician may help guide future policy.

Glutamine in critical illness: the time has come, the time is now.

Glutamine (GLN) has been shown to be a key pharmaconutrient in the body's response to stress and injury. It exerts its protective effects via multiple mechanisms, including direct protection of cells and tissue from injury, attenuation inflammation, and preservation of metabolic function. Data support GLN as an ideal pharmacologic intervention to prevent or treat multiple organ dysfunction syndrome after sepsis or other injuries in the intensive care unit population. A large and growing body of clinical data shows that in well-defined critically ill patient groups GLN can be a life-saving intervention.

Discovery and verification of protein differences between Er positive/Her2/neu negative breast tumor tissue and matched adjacent normal breast tissue.

This study was designed to quantify and identify differences in protein levels between tumor and adjacent normal breast tissue from the same breast in 18 women with stage I/II ER positive/Her2/neu negative invasive breast cancer. Eighteen separate difference gel electrophoresis (DIGE) gels were run (1 gel per patient). Relative quantification was based on DIGE analysis. After excision and tryptic digestion, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and peptide mass mapping were used to identify protein spots. Two hundred and forty-three spots were differentially abundant between normal and cancer tissues. Fifty spots were identified: 41 were over abundant and nine were less abundant in cancers than in normal breast tissue. Western blotting provided independent confirmation for three of the most biologically and statistically interesting proteins. All 18 gels were replicated by another technician and 32% of the differentially abundant proteins were verified by the duplicate analysis. Follow-up studies are now examining these proteins as biomarkers in blood.

Effects of pharmaconutrients on cellular dysfunction and the microcirculation in critical illness.

PURPOSE OF REVIEW: A growing body of data has revealed that specific nutrient deficiencies contribute to microvascular and cellular dysfunction following critical illness. Further, targeted administration of these 'pharmaconutrients' may reverse or improve this dysfunction and improve clinical outcome. RECENT FINDINGS: Specific nutrient therapy with glutamine protects cellular metabolism and vascular function via induction of heat shock proteins, which are key proteins found to be deficient following acute illness. Arginine becomes rapidly deficient following trauma and surgery. This leads to significant immunosuppression, which when treated by arginine administration significantly reduces postoperative infection. Omega-3 fatty acids attenuate the inflammatory response and provide for resolution of ongoing inflammatory injury via production of resolvins/protectins. Antioxidants (vitamin C and selenium) and trace elements (zinc) become rapidly depleted in critical illness and replacement appears vital to ensure optimal cellular and microvascular function. Data on targeted metabolic (mitochondrial) therapies (i.e. co-enzyme Q10) show promise to improve myocardial function following cardiac surgery. SUMMARY: These specific nutrients have newly discovered vital mechanistic roles in the optimization of cellular and microcirculatory function in critical illness and injury. A growing body of literature is demonstrating that correction of key nutrient deficiencies via therapeutic administration of these pharmaconutrients can improve clinical outcome in critically ill patients.

Performance-enhancing sports supplements: role in critical care.

Many performance-enhancing supplements and/or drugs are increasing in popularity among professional and amateur athletes alike. Although the uncontrolled use of these agents can pose health risks in the general population, their clearly demonstrated benefits could prove helpful to the critically ill population in whom preservation and restoration of lean body mass and neuromuscular function are crucial. Post-intensive care unit weakness not only impairs post-intensive care unit quality of life but also correlates with intensive care unit mortality. This review covers a number of the agents known to enhance athletic performance, and their possible role in preservation of muscle function and prevention/treatment of post-intensive care unit weakness in critically ill patients. These agents include testosterone analogues, growth hormone, branched chain amino acid, glutamine, arginine, creatine, and beta-hydryoxy-beta-methylbutyrate. Three of the safest and most effective agents in enhancing athletic performance in this group are creatine, branched-chain amino acid, and beta-hydryoxy-beta-methylbutyrate. However, these agents have received very little study in the recovering critically ill patient suffering from post-intensive care unit weakness. More placebo-controlled studies are needed in this area to determine efficacy and optimal dosing. It is very possible that, under the supervision of a physician, many of these agents may prove beneficial in the prevention and treatment of post-intensive care unit weakness.

Altered metabolic profiles among older mothers with a history of preeclampsia.

Preeclampsia has been linked to increased risk for cardiovascular disease and, more recently, to reduced risk for breast cancer later in life. The altered chronic disease risk associated with prior preeclampsia may reflect underlying metabolic differences. In this case-control study, we examined the metabolic profiles of older mothers with and without a history of preeclampsia in their first pregnancies. At the time of the study, subjects were non-pregnant, non-smoking women who completed their first pregnancies at age 30 or older, were pre-menopausal, and were free of serious chronic disease. Cases were 13 women who experienced preeclampsia in their first pregnancies; controls were 13 women with uncomplicated first pregnancies, frequency matched to cases on race/ethnicity, current age, and age at delivery. A fasting blood sample was collected from each subject during the luteal phase (day 19-22) of the menstrual cycle and assayed for specific factors thought to be linked to hypertensive disease or breast cancer. Compared to women with uncomplicated pregnancies, those with a history of preeclampsia had significantly elevated levels of fasting serum triglycerides, insulin and glucose, and a higher fasting insulin resistance index, suggesting that women with prior preeclampsia were relatively insulin resistant. In addition, cases had higher levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) and a higher molar ratio of IGFBP-3 to IGF-1 than did controls. Adjustment for obesity and other potential confounders did not appreciably alter the magnitude of these associations. This preliminary study suggests that women with a history of preeclampsia have persistent metabolic abnormalities consistent with their observed excess risk for cardiovascular morbidity and mortality, and their apparent reduced risk for breast cancer later in life.

Hypertension-related dietary patterns of rural older adults.

BACKGROUND: Prevalence of hypertension is greater in older adults, and increased intake of fruits, vegetables, and dairy-good sources of potassium, calcium, and magnesium-can reduce blood pressure. This study examined the hypertension-related dietary patterns of older adults. METHODS: A cohort of 180 Pennsylvania adults (aged >/=65), 90 with hypertension, were randomly selected from the Geisinger Rural Aging Study (GRAS). Data were collected by trained interviewers at a home visit. Dietary assessment used five 24-h recalls. We compared the characteristics and dietary intake of people with hypertension to those without hypertension and compared their intakes to current recommendations. RESULTS: Mean intakes of all participants were less than two thirds of the DRI for calcium and magnesium and fell far short of the 3,500 mg of potassium recommended for prevention and treatment of hypertension. Participants with hypertension consumed less sodium than controls. Both groups ate fewer fruits and vegetables than recommended but reached the dairy recommendation. Calcium intake was mainly from high-fat dairy products, beans were the top source of potassium and magnesium. CONCLUSIONS: Older adults with hypertension should be guided to choose more low-fat dairy products and other low-fat calcium sources and to increase intakes of beans, dark green leafy vegetables, and other potassium and magnesium sources.

Genome scan linkage results for longitudinal systolic blood pressure phenotypes in subjects from the Framingham Heart Study.

The relationship between elevated blood pressure and cardiovascular and cerebrovascular disease risk is well accepted. Both systolic and diastolic hypertension are associated with this risk increase, but systolic blood pressure appears to be a more important determinant of cardiovascular risk than diastolic blood pressure. Subjects for this study are derived from the Framingham Heart Study data set. Each subject had five records of clinical data of which systolic blood pressure, age, height, gender, weight, and hypertension treatment were selected to characterize the phenotype in this analysis. We modeled systolic blood pressure as a function of age using a mixed modeling methodology that enabled us to characterize the phenotype for each individual as the individual's deviation from the population average rate of change in systolic blood pressure for each year of age while controlling for gender, body mass index, and hypertension treatment. Significant (p = 0.00002) evidence for linkage was found between this normalized phenotype and a region on chromosome 1. Similar linkage results were obtained when we estimated the phenotype while excluding values obtained during hypertension treatment. The use of linear mixed models to define phenotypes is a methodology that allows for the adjustment of the main factor by covariates. Future work should be done in the area of combining this phenotype estimation directly with the linkage analysis so that the error in estimating the phenotype can be properly incorporated into the genetic analysis, which, at present, assumes that the phenotype is measured (or estimated) without error.