Safety and Feasibility of a Protocolized Daily Assessment of Readiness for Liberation From Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: Decannulation from venovenous extracorporeal membrane oxygenation (ECMO) at the earliest and safest possible time may improve outcomes and reduce cost. Yet, no prospective studies have compared weaning strategies for liberation from ECMO. RESEARCH QUESTION: Is a protocolized daily assessment of readiness to liberate from venovenous ECMO safe and feasible? STUDY DESIGN AND METHODS: We conducted a prospective, single-arm safety and feasibility study of a protocol for daily assessment of readiness to liberate from venovenous ECMO among consecutive adult patients receiving venovenous ECMO across four ICUs at a single center between June 20, 2020, and November 24, 2020. The ECMO-free protocol included three phases: (1) the safety screening, (2) non-ECMO Fio2 titration, and (3) the ECMO-free trial. Enrollment, interventions, and data collection were performed prospectively by trained study staff. RESULTS: Twenty-six patients received the ECMO-free protocol on 385 patient-days. The safety screening was passed during a total of 59 ECMO-free daily assessments (15.3%) among 20 patients. Every passed safety screening proceeded to an ECMO-free trial. Twenty-eight passed ECMO-free trials (47.5%) occurred among 16 patients (61.5%). No missed safety screenings, protocol deviations, or adverse events occurred. Of the 16 patients who passed an ECMO-free trial, 14 patients (87.5%) were decannulated. Among decannulated patients, 12 patients (85.7%) were decannulated on the same day as a passed ECMO-free trial, 6 patients (42.9%) were decannulated on the first day that they passed an ECMO-free trial, and 6 patients (42.9%) passed an ECMO-free trial at least twice consecutively before decannulation. The median time from first passed ECMO-free trial to decannulation was 2 days (interquartile range, 0-3 days). INTERPRETATION: The ECMO-free protocol is feasible and may identify patients for decannulation earlier than gradual approaches to weaning.

Early discontinuation of PD-1 blockade upon achieving a complete or partial response in patients with advanced melanoma: the multicentre prospective Safe Stop trial.

BACKGROUND: The introduction of programmed cell death protein 1 (PD-1) blockers (i.e. nivolumab and pembrolizumab) has significantly improved the prognosis of patients with advanced melanoma. However, the long treatment duration (i.e. two years or longer) has a high impact on patients and healthcare systems in terms of (severe) toxicity, health-related quality of life (HRQoL), resource use, and healthcare costs. While durable tumour responses have been observed and PD-1 blockade is discontinued on an individual basis, no consensus has been reached on the optimal treatment duration. The objective of the Safe Stop trial is to evaluate whether early discontinuation of first-line PD-1 blockade is safe in patients with advanced and metastatic melanoma who achieve a radiological response. METHODS: The Safe Stop trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 200 patients with advanced and metastatic cutaneous melanoma and a confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumours (RECIST) v1.1 will be included to early discontinue first-line monotherapy with nivolumab or pembrolizumab. The primary objective is the rate of ongoing responses at 24 months after discontinuation of PD-1 blockade. Secondary objectives include best overall and duration of response, need and outcome of rechallenge with PD-1 blockade, and changes in (serious) adverse events and HRQoL. The impact of treatment discontinuation on healthcare resource use, productivity losses, and hours of informal care will also be assessed. Results will be compared to those from patients with CR or PR who completed 24 months of treatment with PD-1 blockade and had an ongoing response at treatment discontinuation. It is hypothesised that it is safe to early stop first-line nivolumab or pembrolizumab at confirmed tumour response while improving HRQoL and reducing costs. DISCUSSION: From a patient, healthcare, and economic perspective, shorter treatment duration is preferred and overtreatment should be prevented. If early discontinuation of first-line PD-1 blockade appears to be safe, early discontinuation of PD-1 blockade may be implemented as the standard of care in a selected group of patients. TRIAL REGISTRATION: The Safe Stop trial has been registered in the Netherlands Trial Register (NTR), Trial NL7293 (old NTR ID: 7502), https://www.trialregister.nl/trial/7293 . Date of registration September 30, 2018.

Allocating medical resources fairly: the CSG bioethics guide / Asignación justa de recursos médicos: guía bioética del CSG

Abstract On April 12, 2020, a bioethics guide for allocating scarce hospital resources during the current Covid-19 pandemic was posted on the website of the Consejo de Salubridad General (CSG) of the Government of Mexico. The guide, entitled Guía bioética para asignación de recursos limitados de medicina crítica en situación de emergencia, was intended as a preliminary document, but the website posting did not describe it as a first step in the process. The publicity resulted in a wide array of comments and criticisms. That first version posted on the CSG website contained an age-based criterion for breaking a tie between two or more medically eligible patients who needed of a ventilator: younger patients would have preference over older ones. The final version of the guide eliminated that criterion and instead, relied on the leading public health principle, "save the most lives", without regard to personal characteristics other than the possibility of benefitting from the scarce medical resources.

Resumen El 12 de abril de 2020, se publicó en el sitio web del Consejo de Salubridad General (CSG) del Gobierno de México una guía de bioética para asignar recursos hospitalarios escasos durante la actual pandemia de Covid-19. La guía titulada Guía bioética para asignación de recursos limitados de medicina crítica en situación de emergencia pretendía ser un documento preliminar, pero la publicación en el sitio web no lo describió como un primer paso en el proceso. La publicación resultó en una amplia gama de comentarios y críticas. La primera versión publicada en el sitio web del CSG contenía un criterio basado en la edad para romper el empate entre dos o más pacientes médicamente elegibles que necesitaran un ventilador: los pacientes más jóvenes tendrían preferencia sobre los de mayor edad. La versión final de la guía eliminó ese criterio y, en cambio, se basó en el principio principal de salud pública, "salvar la mayoría de las vidas", sin tener en cuenta las características personales que no sean la posibilidad de beneficiarse de los escasos recursos médicos.

Guía bioética de asignación de recursos de medicina crítica del Consejo de Salubridad General en México / Bioethics guide on scarce medical resource allocation in Mexico

Resumen El tema bioético sobre la asignación de recursos escasos no es nuevo, todos los países que han sido gravemente afectados por el SARS-CoV-2 han tenido que desarrollar y utilizar guías de triaje. Esto resulta más adecuado pues así la asignación de recursos limitados se hace de manera ética y justa, y no de manera discrecional y abierta a la corrupción. En México, en anticipación a la fase exponencial de la pandemia por SARS-CoV-2, el 30 de abril el Consejo de Salubridad General publicó la Guía bioética para asignación de recursos limitados de medicina crítica en situación de emergencia. Dicha guía tiene como base criterios de justicia social y parte de la tesis: todas las vidas tienen el mismo valor. Este texto tiene como objetivo proporcionar las razones bioéticas y biojurídicas que conforman esta guía de triaje en nuestro país. En resumen, proporciona una breve exploración de las razones éticas que justifican cierta manera específica de asignar recursos escasos en medicina crítica, así como del sustento procedimental apegado a los estándares en materia de derechos humanos.

Abstract The bioethical inquiry about allocating fairly scarce health resources is not new, all countries around the world that were seriously afflicted by SARS-CoV-2 have issued triage guidelines in order to address the dilemmas raised by the pandemic. There is no question about the need to create bioethical guidelines, since its creation provides a degree of certainty that fair and ethical decisions are taken. This also prevents that decisions are made in solitary and maybe motivated by corrupted actions. In Mexico, the creation of this guideline was a proactive and preventive measure to what was unavoidable, the exponential contagion phase of the pandemical scenario caused by Covid-19. On April 30, 2020 the General Sanitary Council published the Bioethical Guide to Allocate Scarce Resources on Critical Care Medicine in Emergency Situation. This guide has at its core that principle of utmost importance in social justice which main thesis is: "All lives have the same value". The aim of this contribution is to provide the ethical and legal principles established in the aforementioned bioethical guideline. In sum, a brief exploration of the ethical reasons that support a specific way to allocate scarce health resources is provided, as well as the foundations of the procedural part from a human rights-based approach.

[Bioethics guide on scarce medical resource allocation in Mexico]. / Guía bioética de asignación de recursos de medicina crítica del Consejo de Salubridad General en México.

The bioethical inquiry about allocating fairly scarce health resources is not new, all countries around the world that were seriously afflicted by SARS-CoV-2 have issued triage guidelines in order to address the dilemmas raised by the pandemic. There is no question about the need to create bioethical guidelines, since its creation provides a degree of certainty that fair and ethical decisions are taken. This also prevents that decisions are made in solitary and maybe motivated by corrupted actions. In Mexico, the creation of this guideline was a proactive and preventive measure to what was unavoidable, the exponential contagion phase of the pandemical scenario caused by Covid-19. On April 30, 2020 the General Sanitary Council published the Bioethical Guide to Allocate Scarce Resources on Critical Care Medicine in Emergency Situation. This guide has at its core that principle of utmost importance in social justice which main thesis is: "All lives have the same value". The aim of this contribution is to provide the ethical and legal principles established in the aforementioned bioethi-cal guideline. In sum, a brief exploration of the ethical reasons that support a specific way to allocate scarce health resources is provided, as well as the foundations of the procedural part from a human rights-based approach.

El tema bioético sobre la asignación de recursos escasos no es nuevo, todos los países que han sido gravemente afectados por el SARS-CoV-2 han tenido que desarrollar y utilizar guías de triaje. Esto resulta más adecuado pues así la asignación de recursos limitados se hace de manera ética y justa, y no de manera discrecional y abierta a la corrupción. En México, en anticipación a la fase exponencial de la pandemia por SARS-CoV-2, el 30 de abril el Consejo de Salubridad General publicó la Guía bioética para asignación de recursos limitados de medicina crítica en situación de emergencia. Dicha guía tiene como base criterios de justicia social y parte de la tesis: todas las vidas tienen el mismo valor. Este texto tiene como objetivo propor-cionar las razones bioéticas y biojurídicas que conforman esta guía de triaje en nuestro país. En resumen, proporciona una breve exploración de las razones éticas que justifican cierta manera específica de asignar recursos escasos en medicina crítica, así como del sustento procedimental apegado a los estándares en materia de derechos humanos.

Allocating medical resources fairly:the CSG bioethics guide.

On April 12, 2020, a bioethics guide for allocating scarce hospital resources during the current Covid-19 pandemic was posted on the website of the Consejo de Salubridad General(CSG) of the Government of Mexico. The guide, entitled Guía bioética para asignación de recursos limitados de medicina crítica en situación de emergencia, was intended as a preliminary document, but the website posting did not describe it as a first step in the process. The publicity resulted in a wide array of comments and criticisms. That first version posted on the CSG website contained an age-based criterion for breaking a tie between two or more medically eligible patients who needed of a ventilator: younger patients would have prefer-ence over older ones. The final version of the guide eliminated that criterion and instead, relied on the leading public health principle, "save the most lives", without regard to personal characteristics other than the possibility of benefitting from the scarce medical resources.

El 12 de abril de 2020, se publicó en el sitio web del Consejo de Salubridad General (CSG) del Gobierno de México una guía de bioética para asignar recursos hospitalarios escasos durante la actual pandemia de Covid-19. La guía titulada Guía bioética para asignación de recursos limitados de medicina crítica en situación de emergencia pretendía ser un documento pre-liminar, pero la publicación en el sitio web no lo describió como un primer paso en el proceso. La publicación resultó en una amplia gama de comentarios y críticas. La primera versión publicada en el sitio web del CSG contenía un cri-terio basado en la edad para romper el empate entre dos o más pacientes médicamente elegibles que necesitaran un ventilador: los pacientes más jóvenes tendrían preferencia sobre los de mayor edad. La versión final de la guía eliminó ese criterio y, en cambio, se basó en el principio principal de salud pública, "salvar la mayoría de las vidas", sin tener en cuenta las características personales que no sean la posibilidad de beneficiarse de los escasos recursos médicos.

Perioperative bridging of vitamin K antagonist treatment in patients with atrial fibrillation: only a very small group of patients benefits.

AIMS: Bridging anticoagulation in atrial fibrillation (AF) patients who need to interrupt vitamin K antagonists for procedures is a clinical dilemma. Currently, guidelines recommend clinicians to take the stroke and bleeding risk into consideration, but no clear thresholds are advised. To aid clinical decision making, we aimed to develop a model in which periprocedural bridging therapy is compared with withholding anticoagulation in AF patients, for several bleeding and stroke risk groups. METHODS AND RESULTS: A model was developed to simulate both a bridge and a non-bridge cohort, using simulated international normalized ratio (INR) values for patients on warfarin, acenocoumarol, and phenprocoumon. For both clinical strategies, stroke and bleeding risks were included and outcomes were stratified by CHA2DS2-VASc or CHADS2 and HAS-BLED groups. Quality-adjusted life expectancy was the main outcome considered. Our analyses show bridging to only be beneficial for patients with HAS-BLED scores equal or lower to 2 and with CHA2DS2-VASc scores of 6 or higher. For patients using acenocoumarol bridging may be beneficial starting at a CHA2DS2-VASc score of 7. Post-procedural time to therapeutic INR has a significant influence on the results: no significant benefit of bridging was found for patients reaching therapeutic INR values within 5 days. CONCLUSION: When deciding whether to bridge anticoagulation, clinicians should consider the patient's individual stroke and bleeding risk, while also considering the patient's post-procedural INR management. In practice, only a small subset of patients is expected to benefit from bridging anticoagulation treatment.

When to Stop Eculizumab in Complement-Mediated Thrombotic Microangiopathies.

The terminal complement-inhibitor eculizumab has dramatically changed the management of patients with atypical hemolytic uremic syndrome (aHUS), and has also shown promise for treating certain forms of secondary HUS (sHUS), including that caused by drugs and solid-organ/hematopoietic stem cell transplant. While effective, eculizumab is costly and inconvenient. In this review, we evaluate the literature on eculizumab cessation in these diseases to better inform clinicians who consider stopping therapy. Reported relapse rates in aHUS after stopping eculizumab are as high as 30%, suggesting indefinite therapy is reasonable and that patients who choose to stop should be closely monitored. In sHUS, relapse is rare, justifying short courses of eculizumab.

Stopping Biologics in IBD-What Is the Evidence?

Biologic treatments have revolutionized the way we treat inflammatory bowel disease patients (IBD). Anti-tumor necrosis factor (anti-TNF) antibodies are superior to conventional therapies to achieve sustained remission without steroids and mucosal healing. The objective of IBD treatment has evolved from symptom alleviation to a combination of absence of symptoms and intestinal healing. Nevertheless, biologics are expensive and are associated with an increased risk of infections and possibly skin cancers. Therefore, the duration of these treatments may be questioned, and stopping them may be contemplated by some patients and clinicians, while it is sometimes even imposed by some jurisdictions across the world. In the present paper, I highlight the recent literature about outcomes after biologics withdrawal, patients' profiles associated with these outcomes, monitoring after withdrawal, and results of retreatment. We also introduce the concept of biologic treatment cycles in IBD.

Worldwide end-of-life practice for patients in ICUs.

PURPOSE OF REVIEW: Published data and practice recommendations on end-of-life (EOL) generally reflect Western practice frameworks. Understanding worldwide practices is important because improving economic conditions are promoting rapid expansion of intensive care services in many previously disadvantaged regions, and increasing migration has promoted a new cultural diversity previously predominantly unicultural societies. This review explores current knowledge of similarities and differences in EOL practice between regions and possible causes and implications of these differences. RECENT FINDINGS: Recent observational and survey data shows a marked variability in the practice of withholding and withdrawing life sustaining therapy worldwide. Some evidence supports the view that culture, religion, and socioeconomic factors influence EOL practice, and individually or together account for differences observed. There are also likely to be commonly desired values and expectations for EOL practice, and recent attempts at establishing where worldwide consensus may lie have improved our understanding of shared values and practices. SUMMARY: Awareness of differences, understanding their likely complex causes, and using this knowledge to inform individualized care at EOL is likely to improve the quality of care for patients. Further research should clarify the causes of EOL practice variability, monitor trends, and objectively evaluate the quality of EOL practice worldwide.

ESPEN guideline on ethical aspects of artificial nutrition and hydration.

BACKGROUND: The worldwide debate over the use of artificial nutrition and hydration remains controversial although the scientific and medical facts are unequivocal. Artificial nutrition and hydration are a medical intervention, requiring an indication, a therapeutic goal and the will (consent) of the competent patient. METHODS: The guideline was developed by an international multidisciplinary working group based on the main aspects of the Guideline on "Ethical and Legal Aspects of Artificial Nutrition" published 2013 by the German Society for Nutritional Medicine (DGEM) after conducting a review of specific current literature. The text was extended and introduced a broader view in particular on the impact of culture and religion. The results were discussed at the ESPEN Congress in Lisbon 2015 and accepted in an online survey among ESPEN members. RESULTS: The ESPEN Guideline on Ethical Aspects of Artificial Nutrition and Hydration is focused on the adult patient and provides a critical summary for physicians and caregivers. Special consideration is given to end of life issues and palliative medicine; to dementia and to specific situations like nursing care or the intensive care unit. The respect for autonomy is an important focus of the guideline as well as the careful wording to be used in the communication with patients and families. The other principles of Bioethics like beneficence, non-maleficence and justice are presented in the context of artificial nutrition and hydration. In this respect the withholding and withdrawing of artificial nutrition and/or hydration is discussed. Due to increasingly multicultural societies and the need for awareness of different values and beliefs an elaborated chapter is dedicated to cultural and religious issues and nutrition. Last but not least topics like voluntary refusal of nutrition and fluids, and forced feeding of competent persons (persons on hunger strike) is included in the guideline.

Reducing inappropriate polypharmacy: the process of deprescribing.

Inappropriate polypharmacy, especially in older people, imposes a substantial burden of adverse drug events, ill health, disability, hospitalization, and even death. The single most important predictor of inappropriate prescribing and risk of adverse drug events in older patients is the number of prescribed drugs. Deprescribing is the process of tapering or stopping drugs, aimed at minimizing polypharmacy and improving patient outcomes. Evidence of efficacy for deprescribing is emerging from randomized trials and observational studies. A deprescribing protocol is proposed comprising 5 steps: (1) ascertain all drugs the patient is currently taking and the reasons for each one; (2) consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention; (3) assess each drug in regard to its current or future benefit potential compared with current or future harm or burden potential; (4) prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes; and (5) implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects. Whereas patient and prescriber barriers to deprescribing exist, resources and strategies are available that facilitate deliberate yet judicious deprescribing and deserve wider application.

Ethics and health policy of dialyzing a patient in a persistent vegetative state.

Each year, out-of-hospital cardiac arrests occur in approximately 300,000 Americans. Of these patients, less than 10% survive. Survivors often live with neurologic impairments that neurologists classify as anoxic-ischemic encephalopathy (AIE). Neurologic impairments under AIE can vary widely, each with unique outcomes. According to the American Academy of Neurology Practice Parameter paper, the definition of poor outcome in AIE includes death, persistent vegetative state (PVS), or severe disability requiring full nursing care 6 months after event. In a recent survey, participants deemed an outcome of PVS as "worse than dead." Lay persons' assessments of quality of life for those in a PVS provide assistance for surrogate decision-makers who are confronted with the clinical decision-making for a loved one in a PVS, whereas clinical practice guidelines help health care providers to make decisions with patients and/or families. In 2000, the Renal Physicians Association and the American Society of Nephrology published a clinical practice guideline, "Shared Decision-Making in the Appropriate Initiation of and Withdrawal from Dialysis." In 2010, after advances in research, a second edition of the guideline was published. The updated guideline confirmed the recommendation to withhold or withdraw ongoing dialysis in "patients with irreversible, profound neurological impairments such that they lack signs of thought, sensation, purposeful behavior and awareness of self and environment," such as found in patients with PVS. Here, the authors discuss the applicability of this guideline to patients in a PVS. In addition, they build on the guideline's conception of shared decision-making and discuss how continued dialysis violates ethical and legal principles of care in patients in a PVS.

[How I treat....Recommendations for stopping a pharmacological therapy]. / Recommandations pour interrompre un traitement médicamenteux.

To interrupt a pharmacological treatment is sometimes warranted in clinical practice. It may appear as an easy task, simpler to undertake than the initiation of a new therapy, and, yet, it requires that some conditions be fulfilled and some precautions be taken: (1) the reasons why the medication is interrupted should be clearly explained; (2) the physician should make sure that the interruption, even if transient, is without danger; (3) the modalities of interruption should be clearly determined (immediate cessation vs progressive dose reduction), and, finally, (4) an appropriate follow-up of the duly informed patient should be scheduled.

Withholding and termination of resuscitation of adult cardiopulmonary arrest secondary to trauma: resource document to the joint NAEMSP-ACSCOT position statements.

In the setting of traumatic cardiopulmonary arrest, protocols that direct emergency medical service (EMS) providers to withhold or terminate resuscitation, when clinically indicated, have the potential to decrease unnecessary use of warning lights and sirens and save valuable public health resources. Protocols to withhold resuscitation should be based on the determination that there are no obvious signs of life, the injuries are obviously incompatible with life, there is evidence of prolonged arrest, and there is a lack of organized electrocardiographic activity. Termination of resuscitation is indicated when there are no signs of life and no return of spontaneous circulation despite appropriate field EMS treatment that includes minimally interrupted cardiopulmonary resuscitation. Further research is needed to determine the appropriate duration of cardiopulmonary resuscitation before termination of resuscitation and the proper role of direct medical oversight in termination of resuscitation protocols. This article is the resource document to the position statements, jointly endorsed by the National Association of EMS Physicians and the American College of Surgeons' Committee on Trauma, on withholding and termination of resuscitation in traumatic cardiopulmonary arrest.