Evaluating models of consent in changing health research environments.

While Specific Informed Consent has been the established standard for obtaining consent for medical research for many years, it does not appear suitable for large-scale biobank and health data research. Thus, alternative forms of consent have been suggested, based on a variety of ethical background assumptions. This article identifies five main ethical perspectives at stake. Even though Tiered Consent, Dynamic Consent and Meta Consent are designed to the demands of the self-determination perspective as well as the perspective of research as a public good, they are still also criticized from both perspectives. In addition, criticisms based on concerns of justice, participation and democratic deliberation, and relational concerns have been levelled at each of the models. As all of these perspectives have valid points to make, the task at hand lies in balancing these ethical perspectives. What constitutes an adequate balancing depends on contextual factors. These factors include digital infrastructure and digital literacy, data safety regulation, good scientific and clinical practice, transparent debates on ethically relevant features of research, social inequalities, anti-discrimination laws and practices, trust in health care institutions and recognition of patient preferences, and consensus on unethical research. We argue that the role of context in determining acceptable models of consent puts the ethical importance of models of consent into perspective. Since altering contextual factors can help to live up to the ethical concerns at stake in debates about models of consent, opting for such a shift of focus comes without ethical loss.

Allocating scarce intensive care resources during the COVID-19 pandemic: practical challenges to theoretical frameworks.

The COVID-19 pandemic strained health-care systems throughout the world. For some, available medical resources could not meet the increased demand and rationing was ultimately required. Hospitals and governments often sought to establish triage committees to assist with allocation decisions. However, for institutions operating under crisis standards of care (during times when standards of care must be substantially lowered in the setting of crisis), relying on these committees for rationing decisions was impractical-circumstances were changing too rapidly, occurring in too many diverse locations within hospitals, and the available information for decision making was notably scarce. Furthermore, a utilitarian approach to decision making based on an analysis of outcomes is problematic due to uncertainty regarding outcomes of different therapeutic options. We propose that triage committees could be involved in providing policies and guidance for clinicians to help ensure equity in the application of rationing under crisis standards of care. An approach guided by egalitarian principles, integrated with utilitarian principles, can support physicians at the bedside when they must ration scarce resources.

The concept of vulnerability in medical ethics and philosophy.

BACKGROUND: Healthcare is permeated by phenomena of vulnerability and their ethical significance. Nonetheless, application of this concept in healthcare ethics today is largely confined to clinical research. Approaches that further elaborate the concept in order to make it suitable for healthcare as a whole thus deserve renewed attention. METHODS: Conceptual analysis. RESULTS: Taking up the task to make the concept of vulnerability suitable for healthcare ethics as a whole involves two challenges. Firstly, starting from the concept as it used in research ethics, a more detailed characterization and systematization of the different realms of human abilities and the various ways in which these realms contain vulnerability is to be established. Secondly, at the same time, the sought-after concept of vulnerability should avoid picturing the relation between healthcare recipient and provider as a relation between a dependent individual in need and another individual capable of providing all the help necessary. An adequate concept of vulnerability should enable one to understand when and in which respects care providers may be vulnerable as well. Philosophical accounts of vulnerability can help to meet both of these challenges. CONCLUSIONS: Philosophical accounts of vulnerability can help to make the concept of vulnerability suitable for healthcare ethics as a whole. They come with a price, though. While the ethical role of vulnerability in medical ethics usually is to signify states of affairs that are to be diminished or overcome, philosophical accounts introduce forms of vulnerability that are regarded as valuable. Further analyzing and systematizing forms and degrees of vulnerability thus comprises the task to distinguish between amounts and types of vulnerability that can count as valuable, and amounts and types of vulnerability that are to be alleviated.

Machine metaphors and ethics in synthetic biology.

The extent to which machine metaphors are used in synthetic biology is striking. These metaphors contain a specific perspective on organisms as well as on scientific and technological progress. Expressions such as "genetically engineered machine", "genetic circuit", and "platform organism", taken from the realms of electronic engineering, car manufacturing, and information technology, highlight specific aspects of the functioning of living beings while at the same time hiding others, such as evolutionary change and interdependencies in ecosystems. Since these latter aspects are relevant for, for example, risk evaluation of uncontained uses of synthetic organisms, it is ethically imperative to resist the thrust of machine metaphors in this respect. In addition, from the perspective of the machine metaphor viewing an entity as a moral agent or patient becomes dubious. If one were to regard living beings, including humans, as machines, it becomes difficult to justify ascriptions of moral status. Finally, the machine metaphor reinforces beliefs in the potential of synthetic biology to play a decisive role in solving societal problems, and downplays the role of alternative technological, and social and political measures.

Are older people a vulnerable group? Philosophical and bioethical perspectives on ageing and vulnerability.

The elderly are often considered a vulnerable group in public and academic bioethical debates and regulations. In this paper, we examine and challenge this assumption and its ethical implications. We begin by systematically delineating the different concepts of vulnerability commonly used in bioethics, before then examining whether these concepts can be applied to old age. We argue that old age should not, in and of itself, be used as a marker of vulnerability, since ageing is a process that can develop in a variety of different ways and is not always associated with particular experiences of vulnerability. We, therefore, turn to more fundamental phenomenological considerations in order to reconstruct from a first person perspective the intricate interconnections between the experiences of ageing and vulnerability. According to this account, ageing and old age are phenomena in which the basic anthropological vulnerability of human beings can manifest itself in an increased likelihood of harm and exploitation. Thus, we plead for a combined model of vulnerability that helps to avoid problems related to the current concepts of vulnerability. We conclude first that old age as such is not a sufficient criterion for being categorized as vulnerable in applied ethics, and second that reflections on ageing can help to develop a better understanding of the central role of vulnerability in human existence and in applied ethics.

Do we have a moral obligation to synthesize organisms to increase biodiversity? On kinship, awe, and the value of life's diversity.

Synthetic biology can be understood as expanding the abilities and aspirations of genetic engineering. Nonetheless, whereas genetic engineering has been subject to criticism due to its endangering biodiversity, synthetic biology may actually appear to prove advantageous for biodiversity. After all, one might claim, synthesizing novel forms of life increases the numbers of species present in nature and thus ought to be ethically recommended. Two perspectives on how to spell out the conception of intrinsic value of biodiversity are examined in order to assess this line of thought. At the cost of introducing two separate capacities of human knowledge acquisition, the 'admiration stance' turns out to reject outright the assumption of a synthetic species' intrinsic value and of an imperative to create novel species. The 'kinship stance' by contrast does ascribe value to both synthetic and natural species and organisms. Nonetheless, while from this perspective creating novel species may become an ethical demand under certain conditions, it favours changing organisms by getting in contact with them rather than synthesizing them. It is concluded that neither the admiration nor the kinship stance warrants a supposed general moral obligation to create novel species to increase biodiversity.

Usefulness of monitoring platelet function by multiple electrode aggregometry in primary coronary artery bypass surgery.

OBJECTIVES: Antiplatelet therapy commonly is used for the prevention of cardiovascular complications but increases the risk of perioperative bleeding. Multiple-electrode aggregometry (MEA) was investigated for monitoring platelet inhibition by acetylsalicylic acid (ASA) and clopidogrel in patients undergoing elective coronary artery bypass graft (CABG) surgery with regard to clinical outcome as measured by postoperative blood loss and transfusion requirements. DESIGN: A prospective observational study. SETTING: A teaching hospital. PARTICIPANTS: One hundred fifty patients scheduled for elective CABG surgery were included: without antiplatelet therapy (group A, n = 50), single ASA exposure (group B, n = 50), and combined therapy with ASA and clopidogrel (group C, n = 50). MEASUREMENTS AND MAIN RESULTS: MEA was assessed preoperatively using either collagen (COL-MEA) or ADP (ADP-MEA). Postoperative blood loss and transfusion requirements were recorded for 24 hours after surgery. Postoperative blood loss significantly increased only from combined antiplatelet therapy (group A: 572 ± 297 mL, group B: 721 ± 356 mL, group C: 865 ± 346, p < 0.01) and correlated with ADP (r(p) = -0.35, p < 0.01) and COL-MEA (r(p) = -0.23, p > 0.01). COL-MEA and ADP-MEA discriminated between preoperative ASA and clopidogrel intake (ASA: sensitivity = 86.3%, and specificity = 89.3%; clopidogrel: sensitivity = 87.5%, and specificity = 95.1%). The postoperative transfusion risk was increased in patients diagnosed for clopidogrel treatment by ADP-MEA (odds ratio = 2.92; confidence interval: 1.44-5.92; p = 0.005). CONCLUSIONS: MEA is a suitable method for the detection of platelet inhibition by ASA and clopidogrel in patients undergoing CABG surgery. In these patients, preoperative ADP MEA seems to indicate patients at risk for postoperative transfusion requirements.

Development and feasibility of a scale to assess postoperative recovery: the post-operative quality recovery scale.

BACKGROUND: Good postoperative recovery is increasingly recognized as an important outcome after surgery. The authors created a new Post-operative Quality Recovery Scale (PQRS) that tracks multiple domains of recovery from immediate to long-term time periods in patients of varying ages, languages, and cultures. METHODS: The parameters of importance to both clinicians and patients were identified. After an initial pilot study of 133 patients, the PQRS was refined. It consists of six domains (physiologic, nociceptive, emotive, activities of daily living, cognitive, and overall patient perspective). An observational study of 701 patients was performed with the refined PQRS to assess its capacity to evaluate and track recovery and to discriminate between patients. It was conducted in eight countries and in five languages, involving patients more than or equal to 6 yr undergoing elective surgery with general anesthesia. Recovery was assessed before surgery and at multiple time periods postoperatively. Recovery was defined as return to baseline values or better. RESULTS: Seven hundred one patients completed the PQRS. Mean completion time was 4.8 (SD 2.8) min. Recovery scores improved with time. Physiologic recovery was complete in 34% of subjects by 40 min. By the third postoperative day, complete recovery was obtained in 11% of cases (all domains): 48.7% nociceptive, 81.8% emotive, 68.8% activities of daily living, and only 33.5% cognitive. Overall, 95.8% of the patients reported that they were "satisfied or totally satisfied" with their anesthetic care. CONCLUSION: The scores on the PQRS demonstrated an improvement over time, consistent with an expected recovery after surgery and anesthesia, and an ability to discriminate between individuals. Many patients had incomplete recovery by the third postoperative day.

Volume replacement with a balanced hydroxyethyl starch (HES) preparation in cardiac surgery patients.

OBJECTIVE: Balanced fluids appear to be have advantages over unbalanced fluids for correcting hypovolemia. The effects of a new balanced hydroxyethyl starch (HES) were studied in cardiac surgery patients. DESIGN: Prospective, randomized, unblinded study. SETTING: Clinical study in a single cardiac surgery institution. PARTICIPANTS: Sixty patients undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTION: Patients received either a balanced 6% HES 130/0.4 plus a balanced crystalloid (n = 30) or an unbalanced HES-in-saline plus saline (n = 30) to keep cardiac index >2.5 L/min/m(2). MEASUREMENTS AND MAIN RESULTS: Base excess (BE), kidney function, inflammatory response (interleukins-6, -10), endothelial activation (intercellular adhesion molecule-1 [ICAM]), and coagulation (thromboelastometry, whole blood aggregation) were measured after induction of anesthesia, after surgery and 5 hours later, and at the 1st and 2nd postoperative days; 2,950 +/- 530 mL of balanced and 3,050 +/- 560 mL of unbalanced HES were given. BE was reduced significantly in the unbalanced group (from 1.11 +/- 0.71 mmol/L to -5.11 +/- 0.48 mmol/L after surgery) and remained unchanged in the balanced group. Balanced volume replacement resulted in significantly lower IL-6, IL-10, and ICAM plasma concentrations and lower urine concentrations of kidney-specific proteins than in the unbalanced group. After surgery, thromboelastometry data and platelet function were changed significantly in both groups; 5 hours thereafter they were significantly changed only in the unbalanced group. CONCLUSION: A plasma-adapted HES preparation in addition to a balanced crystalloid resulted in significantly less decline in BE, less increase in concentrations of kidney-specific proteins, less inflammatory response and endothelial damage, and fewer changes in hemostasis compared with an unbalanced fluid strategy.

The impact of fluid therapy on microcirculation and tissue oxygenation in hypovolemic patients: a review.

PURPOSE: An optimal volume replacement strategy aims to restore systemic hemodynamics with the ultimate goals of improving organ perfusion and microcirculation for sustaining adequate tissue oxygenation. This review presents the (patho)physiological basis of hypovolemia, microcirculation, and tissue oxygenation and presents a literature review on the effects of plasma substitutes on microperfusion and oxygenation in the clinical setting. METHODS: Literature review of the effects of fluid therapy on microcirculation and tissue oxygenation using PubMed search including original papers in English from 1988 to 2009. RESULTS: We identified a total of 14 articles dealing with the effects of different crystalloids and colloids on organ perfusion, microcirculation, and tissue oxygenation in patients. The results are divergent, but there is a general trend that colloids are superior to crystalloids in improving organ perfusion, microcirculation, and tissue oxygenation. Due to the limited number of studies and different study conditions, a meta-analysis on the effects of the volume replacement strategies on microcirculation is not possible. CONCLUSIONS: Improving the microcirculation by volume replacement appears to be a promising issue when treating the critically ill. The growing insights from animal experiments have to be translated into the clinical setting to identify the optimal fluid regimen for correcting hypovolemia. New techniques for monitoring microcirculation at the bedside might provide such endpoints, although these have to be validated also in the clinical setting. Whether improved microperfusion and tissue oxygenation by fluid therapy will also improve patient outcomes will have to be proven by future studies.

Goal-directed intraoperative therapy based on autocalibrated arterial pressure waveform analysis reduces hospital stay in high-risk surgical patients: a randomized, controlled trial.

INTRODUCTION: Several studies have shown that goal-directed hemodynamic and fluid optimization may result in improved outcome. However, the methods used were either invasive or had other limitations. The aim of this study was to perform intraoperative goal-directed therapy with a minimally invasive, easy to use device (FloTrac/Vigileo), and to evaluate possible improvements in patient outcome determined by the duration of hospital stay and the incidence of complications compared to a standard management protocol. METHODS: In this randomized, controlled trial 60 high-risk patients scheduled for major abdominal surgery were included. Patients were allocated into either an enhanced hemodynamic monitoring group using a cardiac index based intraoperative optimization protocol (FloTrac/Vigileo device, GDT-group, n = 30) or a standard management group (Control-group, n = 30), based on standard monitoring data. RESULTS: The median duration of hospital stay was significantly reduced in the GDT-group with 15 (12 - 17.75) days versus 19 (14 - 23.5) days (P = 0.006) and fewer patients developed complications than in the Control-group [6 patients (20%) versus 15 patients (50%), P = 0.03]. The total number of complications was reduced in the GDT-group (17 versus 49 complications, P = 0.001). CONCLUSIONS: In high-risk patients undergoing major abdominal surgery, implementation of an intraoperative goal-directed hemodynamic optimization protocol using the FloTrac/Vigileo device was associated with a reduced length of hospital stay and a lower incidence of complications compared to a standard management protocol. CLINICAL TRIAL REGISTRATION INFORMATION: Unique identifier: NCT00549419.

Safety of nonblood plasma substitutes: less frequently discussed issues.

A variety of different fluids are promoted to correct hypovolaemia. Apart from the crystalloid versus colloid debate, there exists also a colloid versus colloid discussion as different protein (albumin) and nonprotein colloids (dextrans, gelatins, hydroxyethyl starch preparations) are available for this purpose. The different plasma substitutes largely differ with regard to their composition and their physicochemical properties. All currently used strategies for correcting hypovolaemia have their pros and cons. At present, there is an ongoing interest in the major problems associated with the use of plasma substitutes such as their influence on coagulation and kidney function. There are, however, also some less often addressed questions concerning the use of plasma substitutes that need to be answered. Although nonblood plasma substitutes are often administered worldwide, there is still uncertainty with regard to using them in pregnancy, effects on cross-matching and blood typing, mixing with other drugs, dose limitations, the risk of calcium-containing and potassium-containing solutions, the risk of producing itching, the influence on blood sugar level or whether warming can be done safely. Unfortunately, data to answer these very practical questions are limited or are even lacking for some plasma substitutes. To further increase safety in the treatment of the hypovolaemic patient, all possible problems must be discussed and contraindications of nonblood plasma substitutes must be clearly defined.

A new plasma-adapted hydroxyethyl starch preparation: in vitro coagulation studies.

OBJECTIVE: Preparing hydroxyethyl starch (HES) in a plasma-adapted solution is supposed to improve safety with regard to coagulation. The influence of a new plasma-adapted HES preparation on coagulation was studied. DESIGN: Operator-blinded, randomized study. SETTING: Laboratory in vitro study. PARTICIPANTS: Fifteen healthy young men scheduled for blood donation. INTERVENTIONS: Blood was diluted by 10%, 30%, and 50% using either a plasma-adapted or nonplasma-adapted (prepared in saline solution) potato-derived 6% HES 130/0.42. Only the composition of the solvent of the 2 HES preparations was different. MEASUREMENTS AND MAIN RESULTS: Rotation thromboelastometry (ROTEM; Pentapharm, Munich, Germany) was used to assess changes in coagulation; whole blood aggregometry with 3 inducers was used to assess effects of dilution with HES on platelet function. Clotting time (CT) and clot formation time were significantly prolonged by 30% and 50% dilution, showing significantly longer times in the non-plasma-adapted than in the plasma-adapted HES group (eg, intrinsic CT at the 30% dilution level: plasma-adapted HES 228 +/- 26 seconds [within normal range] v 269 +/- 29 seconds in the nonplasma-adapted HES group). Clot strengthening and clot firmness were significantly reduced by the non-plasma-adapted HES at the 30% dilution level. Platelet aggregation was significantly more reduced by the non-plasma-adapted HES at the 30% and 50% dilution levels. CONCLUSIONS: Dilution with the nonplasma-adapted HES 130/0.42 was associated with more negative effects on thromboelastometry and platelet aggregation than the same HES 130/0.4 dissolved in a plasma-adapted solution. The benefits of using a plasma-adapted modern HES preparation on blood loss and use of blood/blood products in cardiac surgery need to be studied.

Hepatocellular integrity after parenteral nutrition: comparison of a fish-oil-containing lipid emulsion with an olive-soybean oil-based lipid emulsion.

BACKGROUND AND OBJECTIVE: Parenteral nutrition including lipids might be associated with liver disease. The cause leading to parenteral nutrition-related liver dysfunction remains largely unknown but is likely to be multifactorial. The study was performed to assess the effects of a lipid emulsion based on soybean oil, medium-chain triglycerides, olive and fish oil (SMOFlipid20%) compared with a lipid emulsion based on olive and soybean oil on hepatic integrity. METHODS: In a prospective, randomized, double-blinded trial, 44 postoperative patients with an indication for parenteral nutrition were allocated to one of two regimens: group A (n = 22) received SMOFlipid, group B (n = 22) a lipid emulsion based on olive and soybean oil for 5 days. Aspartate aminotransferase, alanin-aminotransferase, and serum alpha-glutathion S-transferase were measured before the start of parenteral nutrition (d0), at day 2 (d2), and day 5 (d5) after the start of parenteral nutrition. The significance level was defined at a P value of less than 0.05. RESULTS: There was no significant difference at d0, but at d2 and d5, significantly lower aspartate aminotransferase (d2: group A: 27 +/- 13 vs. group B: 47 +/- 36 U l(-1); d5: A: 31 +/- 14 vs. B: 56 +/- 45 U l(-1)), alanin-aminotransferase (d2: A: 20 +/- 12 vs. B: 42 +/- 39 U l(-1); d5: A: 26 +/- 15 vs. B: 49 +/- 44 U l(-1)), and alpha-glutathion S-transferase levels (d2: A: 5 +/- 6 vs. B: 17 +/- 21 U l(-1); d5: A: 6 +/- 7 vs. B: 24 +/- 27 microg l(-1)) were found in soybean oil, medium-chain triglycerides, olive and fish oil group compared with the control group. CONCLUSION: Hepatic integrity was well retained with the administration of SMOFlipid whereas in patients receiving a lipid emulsion based on olive and soybean oil liver enzymes were elevated indicating a lower liver tolerability.