Janet D. Pierce

Consequences of Hyperoxia and the Toxicity of Oxygen in the Lung

Oxygen (O2) is life essential but as a drug has a maximum positive biological benefit and accompanying toxicity effects. Oxygen is therapeutic for treatment of hypoxemia and hypoxia associated with many pathological processes. Pathophysiological processes are associated with increased levels of hyperoxia-induced reactive O2 species (ROS) which may readily react with surrounding biological tissues, damaging lipids, proteins, and nucleic acids. Protective antioxidant defenses can become overwhelmed with ROS leading to oxidative stress. Activated alveolar capillary endothelium is characterized by increased adhesiveness causing accumulation of cell populations such as neutrophils, which are a source of ROS. Increased levels of ROS cause hyperpermeability, coagulopathy, and collagen deposition as well as other irreversible changes occurring within the alveolar space. In hyperoxia, multiple signaling pathways determine the pulmonary cellular response: apoptosis, necrosis, or repair. Understanding the effects of O2 administration is important to prevent inadvertent alveolar damage caused by hyperoxia in patients requiring supplemental oxygenation.

Traumatic Brain Injury and Mitochondrial Dysfunction

Abstract:Traumatic brain injury (TBI) is a major cause of death and disability in the United States and causes mitochondrial damage leading to impaired brain function. The purpose of this review is to (1) describe TBI processes and manifestations, (2) examine the mitochondrial alterations after TBI, specifically increased reactive oxygen species production, decreased bioenergetics and apoptosis and (3) current TBI treatments. There are various degrees of severity of TBI, yet all affect mitochondrial function. Currently, health care professionals use various methods to assess TBI severity—from brain imaging to serum biomarkers. The major cause of TBI-associated brain damage is secondary injury, which is mainly from mitochondrial injury dysfunction. Mitochondrial injury leads to oxidative stress and subsequent apoptosis and decreased cellular energy production. These brain cellular alterations impair neurologic functions, which are observed in individuals with TBI. The complex mitochondrial dysfunction after TBI requires treatment that specifically addresses the secondary injury. There are numerous therapies being used, including (1) hypothermia, (2) hyperbaric oxygen, (3) exercise and (4) antioxidants. Researchers are exploring novel approaches to prevent, diagnose and treat TBI focusing on maintaining mitochondrial function.

Flow cytometry and laser scanning cytometry, a comparison of techniques

ObjectiveFlow and laser scanning cytometry are used extensively in research and clinical settings. These techniques provide clinicians and scientists information about cell functioning in a variety of health and disease states. An in-depth knowledge and understanding of cytometry techniques can enhance interpretation of current research findings. Our goal with this review is to reacquaint clinicians and scientists with information concerning differences between flow and laser scanning cytometry by comparing their capabilities and applications.MethodsA Pubmed abstract search was conducted for articles on research, reviews and current texts relating to origins and use of flow and laser scanning cytometry. Attention was given to studies describing application of these techniques in the clinical setting.ResultsBoth techniques exploit interactions between the physical properties of light. Data are immediately and automatically acquired; they are distinctly different. Flow cytometry provides valuable rapid information about a wide variety of cellular or particle characteristics. This technique does not provide the scanned high resolution image analysis needed for investigators to localize areas of interest within the cell for quantification. Flow cytometry requires that the sample contain a large amount disaggregated, single, suspended cells. Laser scanning cytometry is slide-based and does not require as large of a sample. The tissue sample is affixed to a slide allowing repeated sample analyses. These cytometry techniques are used in the clinical setting to understand pathophysiological derangements associated with many diseases; cardiovascular disease, diabetes, acute lung injury, hemorrhagic shock, surgery, cancer and Alzheimer’s disease.ConclusionsUnderstanding the dif- ferences between FCM and LSCM can assist investigators in planning and design of their research or clinical testing. Researchers and clinicians optimize these technique capa- bilities with the cellular characteristics they wish to measure delineating molecular and cellular events occurring in health and disease. Discovery of mechanisms in cells using FCM and LSCM provide evidence needed to guide future treatment and interventions.

Head-of-Bed Elevation and Early Outcomes of Gastric Reflux, Aspiration and Pressure Ulcers: A Feasibility Study

BACKGROUND Guidelines recommending head of bed (HOB) elevation greater than 30º to prevent ventilator-associated pneumonia conflict with guidelines to prevent pressure ulcers, which recommend HOB elevation less than 30º. OBJECTIVES To examine the feasibility of 45º HOB elevation and describe and compare the occurrence of reflux, aspiration, and pressure ulcer development at 30º and 45º HOB elevation. METHODS A randomized 2-day crossover trial was conducted. HOB angle was measured every 30 seconds. Oral and tracheal secretions were analyzed for pepsin presence. Skin was assessed for pressure ulcers. Wilcoxon signed rank tests and Kendall τ correlations were conducted. RESULTS Fifteen patients were enrolled; 11 completed both days. Patients were maintained at 30º (mean, 30º) for 96% of minutes and at 45º (mean, 39º) for 77% of minutes. No patients showed signs of pressure ulcers. A total of 188 oral secretions were obtained, 82 (44%) were pepsin-positive; 174 tracheal secretions were obtained, 108 (62%) were pepsin-positive. The median percentage of pepsin-positive oral secretions was not significantly higher (P = .11) at 30º elevation (54%) than at 45º elevation (20%). The median percentage of pepsin-positive tracheal secretions was not significantly higher (P = .37) at 30º elevation (71%) than 45º elevation (67%). Deeper sedation correlated with increased reflux (P = .03). CONCLUSIONS HOB elevation greater than 30º is feasible and preferred to 30º for reducing oral secretion volume, reflux, and aspiration without pressure ulcer development in gastric-fed patients receiving mechanical ventilation. More deeply sedated patients may benefit from higher HOB elevations.

Understanding the effects of oxygen administration in haemorrhagic shock

AIMS AND OBJECTIVES the aim of this article is to provide a review of the literature regarding oxygen administration and the use of oxygen in patients experiencing haemorrhagic shock (HS). RESULTS oxygen is administered to patients to assist them in maintaining oxygenation. The administration of oxygen is complex and varies significantly among patients. In order to optimize patient care, clinicians need to be aware of the potential effects, both beneficial and harmful, that oxygen can have on the body. INCLUSION AND EXCLUSION CRITERIA literature inclusion criteria for this article was any article (1995 to present) pertaining to oxygen administration and HS. Also included were articles related to tissue injury caused by an overabundance of free radicals with the administration of oxygen. Articles related to oxygen and wound healing, pollution, aerospace, food and industrial uses were excluded. CONCLUSIONS this review of the literature provides an overview of the use of oxygen in clinical practice and HS. The harmful effects of oxygen are highlighted to alert the clinician to this potential when there is an overabundance of oxygen. RELEVANCE TO CLINICAL PRACTICE oxygen is one of the most common drugs used in the medical community; however, the effects of oxygen on the body are not well understood. The use of oxygen if not prescribed correctly can cause cellular damage and death. Clinicians need to be more aware of the effects of oxygen and the damage it may cause if not administered properly.

Treatment and prevention of diaphragm fatigue using low-dose dopamine.

There is increasing evidence that diaphragm fatigue is a major cause of failure in weaning patients frommechanical ventilation. Patients in intensive care units are often administered dopamine to improve renal blood flow without regard to its effect on diaphragmblood flow. The aimof this study was to investigate if intravenous low-dose dopamine, equivalent to the dose used in intensive care units, can treat and prevent diaphragmfatigue. Diaphragmfatigue was produced in anesthetized rats by inspiratory resistance loading (IRL). The effect on diaphragmshortening, diaphragmblood flow, and aortic blood flow was determined. When diaphragm fatigue was attained, group I was given saline for 30 min while maintaining IRL. At the time of diaphragm fatigue, group II was given low-dose dopamine (2 μg/kg/min) for 30 min while maintaining IRL. In group III, dopamine administration was started before and continued throughout the period of IRL. Administering dopamine after the development of diaphragm fatigue (group II) increased diaphragm performance as measured by increased diaphragmshortening and was accompanied by an increased diaphragmblood flow. Administering dopamine prior to and throughout IRL (group III) prevented diaphragmfatigue. Low-dose dopamine can prevent and/or reverse diaphragmfatigue in rats without a significant change in aortic blood flow. This effect of dopamine may be due to increased oxygen delivery associated with the increased diaphragm blood flow, resulting in less free radical formation and thus less muscle damage.

Comparison of a Visual to a Computer Assisted Technique for Detecting Apoptosis

In many studies, fluorescent dyes (ethidium bromide [EB] and acridine orange [AO]) are used to stain DNA to determine if nuclei are apoptotic. However, there are numerous visual methods for counting these stained DNA that may lead to inaccuracies Measuring apoptosis by the visual counting method may be imprecise because of the variability of individuals’ perception of color. Therefore, the authors compared a visual method of counting chromatin for apoptosis with a method relying on a computer program. They began counting chromatin using the visual method, in which individuals identify the stained DNA using their own visual perception. For comparison, they used a software-based counting method (analySIS software) to determine the color (hue) of the stained DNA. Using the numeric hue values from the software eliminates the variations in human color perception. Intra and interrater reliability of the visual and computerassisted counting methods were evaluated with Spearman’s. The authors found statistical significance in the intrarater reliability (r = 1.0,P = 0.0001 for all chromatin categories) and interrater reliability (r = 0.975,P = 0.005 for both readings) when using the software program. No statistical significance was found for the visual counting method, indicating inaccuracy between and within raters. Thus, the computerassisted counting method of identifying the damaged DNA is more accurate and precise than the individual’s visual perception of color. Based on these data, apoptosis measurements using color staining with EB and AO should be determined using hue values generated by a computer program and not by a researcher’s visual assessment.

Systems biology in critical-care nursing.

Systems biology applies advances in technology and new fields of study including genomics, transcriptomics, proteomics, and metabolomics to the development of new treatments and approaches of care for the critically ill and injured patient. An understanding of systems biology enhances a nurses ability to implement evidence-based practice and to educate patients and families on novel testing and therapies. Systems biology is an integrated and holistic view of humans in relationship with the environment. Biomarkers are used to measure the presence and severity of disease and are rapidly expanding in systems biology endeavors. A systems biology approach using predictive, preventive, and participatory involvement is being utilized in a plethora of conditions of critical illness and injury including sepsis, cancer, pulmonary disease, and traumatic injuries.

Exploring leadership roles, goals, and barriers among Kansas registered nurses: A descriptive cross-sectional study

OBJECTIVES The Institute of Medicines Future of Nursing report advocates for full nurse leader representation across multiple settings to address current challenges in our health care system. The purpose of this study was to examine nursing leadership development needs among Kansas registered nurses (RNs). METHODS Data were collected through an online survey and analyzed using quantitative and qualitative methods. RESULTS Nearly 1,000 Kansas RNs participated. Most reported holding one or more leadership positions. Prevalent leadership goals were health care organization volunteer administrative roles. The most frequently identified barrier to developing leadership roles was time constraints. Many wanted to develop skills to serve on a board, 20% were interested in personal leadership development, and 19% in policy development. CONCLUSIONS Based on the findings, the Kansas Action Coalition leadership team is developing programs to address the leadership needs of Kansas RNs. By building capacity in advanced leadership roles, RNs will be better prepared serve as full partners and lead efforts to promote the health of Kansans.

Effect of dopamine on rat diaphragm apoptosis and muscle performance

The purpose of this study was to determine whether dopamine (DA) decreases diaphragm apoptosis and attenuates the decline in diaphragmatic contractile performance associated with repetitive isometric contraction using an in vitro diaphragm preparation. Strenuous diaphragm contractions produce free radicals and muscle apoptosis. Dopamine is a free radical scavenger and, at higher concentrations, increases muscle contractility by simulating β2‐adrenoreceptors. A total of 47 male Sprague–Dawley rats weighing 330–450 g were used in a prospective, randomized, controlled in vitro study. Following animal anaesthetization, diaphragms were excised, and muscle strips prepared and placed in a temperature‐controlled isolated tissue bath containing Krebs–Ringer solution (KR) or KR plus 100 μm DA. The solutions were equilibrated with oxygen (O2) at 10, 21 or 95% and 5% carbon dioxide, with the balance being nitrogen. Diaphragm isometric twitch and subtetanic contractions were measured intermittently over 65 min. The diaphragms were then removed and, using a nuclear differential dye uptake method, the percentages of normal, apoptotic and necrotic nuclei were determined using fluorescent microscopy. There were significantly fewer apoptotic nuclei in the DA group diaphragms than in the KR‐only group diaphragms in 10 and 21% O2 following either twitch or subtetanic contractions. Dopamine at 100 μm produced only modest increases in muscle performance in both 10 and 21% O2. The attenuation of apoptosis by DA was markedly greater than the effect of DA on muscle performance. Dopamine decreased diaphragmatic apoptosis, perhaps by preventing the activation of intricate apoptotic pathways, stimulating antiapoptotic mechanisms and/or scavenging free radicals.