The effectiveness of ambulatory continuous popliteal sciatic nerve blockade on patient-reported overall benefit of analgesia in patients undergoing foot or ankle surgery (CAREFREE trial); a randomized, open label, non-inferiority trial.

STUDY OBJECTIVE: Management of pain after foot and ankle surgery remains a concern for patients and healthcare professionals. This study determined the effectiveness of ambulatory continuous popliteal sciatic nerve blockade, compared to standard of care, on overall benefit of analgesia score (OBAS) in patients undergoing foot or ankle surgery. We hypothesized that usage of ambulatory continuous popliteal sciatic nerve blockade is non-inferior to standard of care. DESIGN: Single center, randomized, non-inferiority trial. SETTING: Tertiary hospital in the Netherlands. PATIENTS: Patients were enrolled if ≥18 years and scheduled for elective inpatient foot or ankle surgery. INTERVENTION: Patients were randomized to ambulatory continuous popliteal sciatic nerve blockade or standard of care. MEASUREMENTS: The primary outcome was the difference in OBAS, which includes pain, side effects of analgesics, and patient satisfaction, measured daily from the first to the third day after surgery. A non-inferiority margin of 2 was set as the upper limit for the 90% confidence interval of the difference in OBAS score. Mixed-effects modeling was employed to analyze differences in OBAS scores over time. Secondary outcome was the difference in opioid consumption. MAIN RESULTS: Patients were randomized to standard of care (n = 22), or ambulatory continuous popliteal sciatic nerve blockade (n = 22). Analyzing the first three postoperative days, the OBAS was significantly lower over time in the ambulatory continuous popliteal sciatic nerve blockade group compared to standard of care, demonstrating non-inferiority (-1.9 points, 90% CI -3.1 to -0.7). During the first five postoperative days, patients with ambulatory continuous popliteal sciatic nerve blockade consumed significantly fewer opioids over time compared to standard of care (-8.7 oral morphine milligram equivalents; 95% CI -16.1 to -1.4). CONCLUSIONS: Ambulatory continuous popliteal sciatic nerve blockade is non-inferior to standard of care with single shot popliteal sciatic nerve blockade on patient-reported overall benefit of analgesia.

Adductor canal block techniques do not lead to involvement of sciatic nerve branches: a radiological cadaveric study.

INTRODUCTION: Low and high volume mid-thigh (ie, distal femoral triangle) and distal adductor canal block approaches are frequently applied for knee surgical procedures. Although these techniques aim to contain the injectate within the adductor canal, spillage into the popliteal fossa has been reported. While in theory this could improve analgesia, it might also result in motor blockade due to coverage of motor branches of the sciatic nerve. This radiological cadaveric study, therefore, investigated the incidence of coverage of sciatic nerve divisions after various adductor canal block techniques. METHODS: Eighteen fresh, unfrozen and unembalmed human cadavers were randomized to receive ultrasound-guided distal femoral triangle or distal adductor canal injections, with 2 mL or 30 mL injectate volume, on both sides (36 blocks in total). The injectate was a 1:10 dilution of contrast medium in local anesthetic. Injectate spread was assessed using whole-body CT with reconstructions in axial, sagittal and coronal planes. RESULTS: No coverage of the sciatic nerve or its main divisions was found. The contrast mixture spread to the popliteal fossa in three of 36 nerve blocks. Contrast reached the saphenous nerve after all injections, whereas the femoral nerve was always spared. CONCLUSIONS: Adductor canal block techniques are unlikely, even when using larger volumes, to block the sciatic nerve, or its main branches. Furthermore, injectate reached the popliteal fossa in a small minority of cases, yet if a clinical analgesic effect is achieved by this mechanism is still unknown.

A radiological cadaveric study of obturator nerve involvement and cranial injectate spread after different approaches to the fascia iliaca compartment block.

Whether the fascia iliaca compartment block (FICB) involves the obturator nerve (ON) remains controversial. Involvement may require that the injectate spreads deep in the cranial direction, and might thus depend on the site of injection. Therefore, the effect of suprainguinal needle insertion with five centimeters of hydrodissection-mediated needle advancement (S-FICB-H) on ON involvement and cranial injectate spread was studied in this radiological cadaveric study. Results were compared with suprainguinal FICB without additional hydrodissection-mediated needle advancement (S-FICB), infrainguinal FICB (I-FICB), and femoral nerve block (FNB). Seventeen human cadavers were randomized to receive ultrasound-guided nerve block with a 40 mL solution of local anesthetic and contrast medium, on both sides. Injectate spread was objectified using computed tomography. The femoral and lateral femoral cutaneous nerves were consistently covered when S-FICB-H, S-FICB or FNB was applied, while the ON was involved in only one of the 34 nerve blocks. I-FICB failed to provide the same consistency of nerve involvement as S-FICB-H, S-FICB or FNB. Injectate reached most cranial in specimens treated with S-FICB-H. Our results demonstrate that even the technique with the most extensive cranial spread (S-FICB-H) does not lead to ON involvement and as such, the ON seems unrelated to FICB. Separate ON block should be considered when clinically indicated.

Ethics of ICU triage during COVID-19.

INTRODUCTION: The coronavirus disease 2019 pandemic has placed intensive care units (ICU) triage at the center of bioethical discussions. National and international triage guidelines emerged from professional and governmental bodies and have led to controversial discussions about which criteria-e.g. medical prognosis, age, life-expectancy or quality of life-are ethically acceptable. The paper presents the main points of agreement and disagreement in triage protocols and reviews the ethical debate surrounding them. SOURCES OF DATA: Published articles, news articles, book chapters, ICU triage guidelines set out by professional societies and health authorities. AREAS OF AGREEMENT: Points of agreement in the guidelines that are widely supported by ethical arguments are (i) to avoid using a first come, first served policy or quality-adjusted life-years and (ii) to rely on medical prognosis, maximizing lives saved, justice as fairness and non-discrimination. AREAS OF CONTROVERSY: Points of disagreement in existing guidelines and the ethics literature more broadly regard the use of exclusion criteria, the role of life expectancy, the prioritization of healthcare workers and the reassessment of triage decisions. GROWING POINTS: Improve outcome predictions, possibly aided by Artificial intelligence (AI); develop participatory approaches to drafting, assessing and revising triaging protocols; learn from experiences with implementation of guidelines with a view to continuously improve decision-making. AREAS TIMELY FOR DEVELOPING RESEARCH: Examine the universality vs. context-dependence of triaging principles and criteria; empirically test the appropriateness of triaging guidelines, including impact on vulnerable groups and risk of discrimination; study the potential and challenges of AI for outcome and preference prediction and decision-support.

Patient data and patient rights: Swiss healthcare stakeholders' ethical awareness regarding large patient data sets - a qualitative study.

BACKGROUND: There is a growing interest in aggregating more biomedical and patient data into large health data sets for research and public benefits. However, collecting and processing patient data raises new ethical issues regarding patient's rights, social justice and trust in public institutions. The aim of this empirical study is to gain an in-depth understanding of the awareness of possible ethical risks and corresponding obligations among those who are involved in projects using patient data, i.e. healthcare professionals, regulators and policy makers. METHODS: We used a qualitative design to examine Swiss healthcare stakeholders' experiences and perceptions of ethical challenges with regard to patient data in real-life settings where clinical registries are sponsored, created and/or used. A semi-structured interview was carried out with 22 participants (11 physicians, 7 policy-makers, 4 ethical committee members) between July 2014 and January 2015. The interviews were audio-recorded, transcribed, coded and analysed using a thematic method derived from Grounded Theory. RESULTS: All interviewees were concerned as a matter of priority with the needs of legal and operating norms for the collection and use of data, whereas less interest was shown in issues regarding patient agency, the need for reciprocity, and shared governance in the management and use of clinical registries' patient data. This observed asymmetry highlights a possible tension between public and research interests on the one hand, and the recognition of patients' rights and citizens' involvement on the other. CONCLUSIONS: The advocation of further health-related data sharing on the grounds of research and public interest, without due regard for the perspective of patients and donors, could run the risk of fostering distrust towards healthcare data collections. Ultimately, this could diminish the expected social benefits. However, rather than setting patient rights against public interest, new ethical approaches could strengthen both concurrently. On a normative level, this study thus provides material from which to develop further ethical reflection towards a more cooperative approach involving patients and citizens in the governance of their health-related big data.

Does organ selling violate human dignity?

Shortages in the number of donated organs after death and the growing number of end-stage organ failure patients on waiting lists call for looking at alternatives to increase the number of organs that could be used for transplantation purposes. One option that has led to a legal and ethical debate is to have regulated markets in human organs. Opponents of a market in human organs offer different arguments that are mostly founded on contingent factors that can be adjusted. However, some authors have asked the question whether we still have a reason to believe that there is something wrong with offering human organs for sale for transplantation purposes, even if the circumstances under which the practice takes place are improved. One prominent argument regarding this appeals to the notion of human dignity. It is argued that organ selling violates human dignity. This paper presents a systematic discussion of dignity-based arguments in the organ selling debate, and then develops a social account of dignity. It is argued that allowing the practice of organ selling inherently runs the risk of promoting the notion that some persons have less worth than others and that persons have a price, which is incompatible with dignity. The approach is defended against possible objections and it is shown that it can capture the notion that autonomy is linked to human dignity in important ways, while dignity at the same time can constrain the autonomous choices of persons with regards to certain practices.

Viscoelastic Testing in Trauma.

Traumatic-induced coagulopathy (TIC) is a complex condition which develops both as a response to trauma as well as to clinical care interventions. Accurate and timely diagnostics are necessary to enable therapy aimed at correction of TIC. Viscoelastic hemostatic assays (VHA) are increasingly recognized for their potential to diagnose TIC as well as for guidance of treatment. This narrative review focuses on the evidence of the use of VHAs to diagnose TIC, to monitor efficacy of treatment of TIC during bleeding and to prognosticate outcome. Pitfalls of the use of VHA are also discussed.

Minimum local anesthetic volumes for a selective saphenous nerve block: a dose-finding study.

BACKGROUND: Saphenous nerve block contributes to analgesia after knee and lower leg surgery. However, literature reports a wide range of volumes of local anesthetic being used for this block. METHODS: A non-randomized controlled trial in a single university hospital in March 2015. Eighteen healthy volunteers (ASA 1 status, aged 27-43 years; male-to-female ratio 11/7) were needed to determine the minimum local anesthetic volume (MLAV) of mepivacaine 2% using the Dixon up-and-down method to achieve a selective ultrasound-guided saphenous nerve block. The primary endpoint MLAV (ED50 and ED95) for an ultrasound-guided saphenous nerve block were determined. The secondary endpoints were the position of the saphenous nerve, block onset and duration of action, cutaneous spread of the block, and the occurrence of femoral nerve motor block. RESULTS: The measured MLAV dose that was effective in 50% of cases (ED50) for a complete saphenous nerve block was 1.5 mL; the calculated MLAV dose for 95% of cases (ED95) was 1.9 mL. The saphenous nerve was encountered in almost all cases on the anterior/anteromedial aspect of the femoral artery. We found no correlation between local anesthetic volume and the onset or duration of the block. Cutaneous spread of the nerve block was observed on the anteromedial aspect of the lower leg, with considerable individual variation between individuals in the study. No femoral motor block was observed. CONCLUSIONS: For a selective ultrasound-guided saphenous nerve block, the ED95 MLAV of mepivacaine 2% is 1.9 mL.

Hemorrhagic-Induced Cardiovascular Complications During Reamer-Irrigator-Aspirator-Assisted Femoral Nonunion Treatment.

UNLABELLED: The reamer-irrigator-aspirator (RIA) is a device that has recently been developed to retrieve bone graft from the medullary canal of the femur and the tibia. As for most new surgical procedures, complications arise as part of the learning curve and/or imperfections in the design or technique. To increase awareness of potential complications and to prevent unnecessary harm to the patient, new complications need to be reported. We present case reports of 2 patients who developed severe intraoperative cardiac events presumably caused by excessive and rapid blood loss during RIA bone graft harvesting. This complication has not been described before. Increased awareness of excessive blood loss and subsequent cardiac events during an RIA procedure is warranted. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Effects of a hospital-wide introduction of a massive transfusion protocol on blood product ratio and blood product waste.

BACKGROUND: Massive transfusion protocols (MTPs) are increasingly used in the transfusion practice and are developed to provide the standardized and early delivery of blood products and procoagulant agents and to supply the transfusion of blood products in a well-balanced ratio. AIM: The aim of this study was to investigate the effect of a hospital-wide introduction of an MTP on blood product ratio and a waste of blood products. MATERIALS AND METHODS: Retrospective analysis was performed to compare the transfusion practice in massive bleeding patients before and after the introduction of an MTP and between the use of an MTP and transfusion off-protocol. Massive bleeding was defined as an administration of ≥5 units of red blood cells (RBCs) within 12 h. RESULTS: Of 547 massively transfused patients, 192 patients were included in the pre-MTP period and 355 patients in the MTP period. The ratio of RBC to fresh frozen plasma (FFP) and the platelets transfused shifted significantly toward 1:1:1 in the MTP period (P = 0.012). This was mainly caused by a shift in RBC: FFP ratio (P = 0.014). An increase in the waste of blood products was observed, most notably FFPs (P = 0.026). Extending the storage time after thawing reduced the waste of FFPs from 11% to 4%. CONCLUSION: Hospital-wide introduction of an MTP is an adequate way to achieve a well-balanced transfusion ratio of 1:1:1. This comes at the cost of an increase in the waste of FFPs, which is lowered after extending the duration of storage time after thawing.

Ideas of Perfection and the Ethics of Human Enhancement.

Whatever ethical stance one takes in the debate regarding the ethics of human enhancement, one or more reference points are required to assess its morality. Some have suggested looking at the bioethical notions of safety, justice, and/or autonomy to find such reference points. Others, arguing that those notions are limited with respect to assessing the morality of human enhancement, have turned to human nature, human authenticity, or human dignity as reference points, thereby introducing some perfectionist assumptions into the debate. In this article, we ask which perfectionist assumptions should be used in this debate. After a critique of views that are problematic, we take a positive approach, suggesting some perfectionist elements that can lend guidance to the practice of human enhancement, based on the work of Martha Nussbaum's Capability Approach. We suggest that the central capabilities can be used to define the human aspect of human enhancement and thereby allow a moral evaluation of enhancement interventions. These central capabilities can be maximized harmoniously to postulate what an ideal human would look like. Ultimately, the aim of this article is twofold. First, it seeks to make explicit the perfectionist assumptions found in the debate and eliminate those that are problematic. Second, the paper clarifies an element that is often neglected in the debate about human enhancement, the view of the ideal human towards which human enhancement should strive. Here, we suggest that some central capabilities that are essential for an ideal human being can be maximized harmoniously and can therefore serve as possible reference points to guide human enhancement.

Evaluating human enhancements: the importance of ideals.

Is it necessary to have an ideal of perfection in mind to identify and evaluate true biotechnological human "enhancements", or can one do without? To answer this question we suggest employing the distinction between ideal and non-ideal theory, found in the debate in political philosophy about theories of justice: the distinctive views about whether one needs an idea of a perfectly just society or not when it comes to assessing the current situation and recommending steps to increase justice. In this paper we argue that evaluating human enhancements from a non-ideal perspective has some serious shortcomings, which can be avoided when endorsing an ideal approach. Our argument starts from a definition of human enhancement as improvement, which can be understood in two ways. The first approach is backward-looking and assesses improvements with regard to a status quo ante. The second, a forward-looking approach, evaluates improvements with regard to their proximity to a goal or according to an ideal. After outlining the limitations of an exclusively backward-looking view (non-ideal theory), we answer possible objections against a forward-looking view (ideal theory). Ultimately, we argue that the human enhancement debate would lack some important moral insights if a forward-looking view of improvement is not taken into consideration.

Human enhancement and perfection.

Both, bioconservatives and bioliberals, should seek a discussion about ideas of human perfection, making explicit their underlying assumptions about what makes for a good human life. This is relevant, because these basic, and often implicit ideas, inform and influence judgements and choices about human enhancement interventions. Both neglect, and polemical but inconsistent use of the complex ideas of perfection are leading to confusion within the ethical debate about human enhancement interventions, that can be avoided by tackling the notion of perfection directly. In the recent debates, bioconservatives have prominently argued against the 'pursuit of perfection' by biotechnological means. In the first part of this paper, we show that--paradoxically--bioconservatives themselves explicitly embrace specific conceptions of human perfection and perfectionist assumptions about the good human life in order to argue against the use of enhancement technologies. Yet, we argue that the bioconservative position contains an untenable ambiguity between criticising and endorsing ideas of human perfection. Hence, they stand in need of clarifying their stance on human perfection. In the second part of the paper, we ask whether bioliberals in fact (implicitly) advocate a particular conception of perfection, or whether they are right in holding that they do not, and that discussing perfection is obsolete anyway. We show that bioliberals also rely on a specific idea of human perfection, based on the idea of autonomy. Hence, their denial of the relevance of perfection in the debate is unconvincing and has to be revised.

Sequence and length recognition of the C-terminal turnover element of LpxC, a soluble substrate of the membrane-bound FtsH protease.

The membrane-anchored FtsH protease is essential in Escherichia coli as it adjusts the cellular amount of LpxC, the key enzyme in lipopolysaccharide (LPS) biosynthesis. Both accumulation and depletion of LpxC are toxic to E. coli. By continuous proteolysis of LpxC, FtsH maintains a low concentration of LpxC and, hence, the proper equilibrium between LPS and phospholipids. The C terminus of LpxC is required for turnover. By adding this tail to glutathione-S-transferase (GST) we show that it is necessary but not sufficient for FtsH-mediated degradation. A detailed mutational analysis revealed six non-polar residues in the C terminus of LpxC that are critical for degradation. Alteration of the C-terminal AVLA motif towards the SsrA-like sequence ALAA directed LpxC to other cellular proteases reinforcing the importance of the C-terminal tail for targeting to FtsH. Short C-terminal truncations stabilized LpxC. Most mutations in the C terminus of LpxC left its enzymatic activity intact as was shown by growth assays, microscopy and 2-keto-3-deoxyoctonate (KDO) determination. The critical length of the turnover element was defined by internal deletions. A C-terminal tail of about 20 amino acids length is required for proteolysis of LpxC by FtsH.