CYP2D6 phenotypes and opioid metabolism: the path to personalized analgesia.

INTRODUCTION: Opioids play a fundamental role in chronic pain, especially considering when 1 of 5 Europeans adults, even more in older females, suffer from it. However, half of them do not reach an adequate pain relief. Could pharmacogenomics help to choose the most appropriate analgesic drug? AREAS COVERED: The objective of the present narrative review was to assess the influence of cytochrome P450 2D6 (CYP2D6) phenotypes on pain relief, analgesic tolerability, and potential opioid misuse. Until December 2021, a literature search was conducted through the MEDLINE, PubMed database, including papers from the last 10 years. CYP2D6 plays a major role in metabolism that directly impacts on opioid (tramadol, codeine, or oxycodone) concentration with differences between sexes, with a female trend toward poorer pain control. In fact, CYP2D6 gene variants are the most actionable to be translated into clinical practice according to regulatory drug agencies and international guidelines. EXPERT OPINION: CYP2D6 genotype can influence opioids' pharmacokinetics, effectiveness, side effects, and average opioid dose. This knowledge needs to be incorporated in pain management. Environmental factors, psychological together with genetic factors, under a sex perspective, must be considered when you are selecting the most personalized pain therapy for your patients.

Consensus for the management of analgesia, sedation and delirium in adults with COVID-19-associated acute respiratory distress syndrome. / Consenso para el manejo de la analgesia, sedación y delirium en adultos con síndrome de distrés respiratorio agudo por COVID-19.

OBJECTIVE: To propose agile strategies for a comprehensive approach to analgesia, sedation, delirium, early mobility and family engagement for patients with COVID-19-associated acute respiratory distress syndrome, considering the high risk of infection among health workers, the humanitarian treatment that we must provide to patients and the inclusion of patients' families, in a context lacking specific therapeutic strategies against the virus globally available to date and a potential lack of health resources. METHODS: A nonsystematic review of the scientific evidence in the main bibliographic databases was carried out, together with national and international clinical experience and judgment. Finally, a consensus of recommendations was made among the members of the Committee for Analgesia, Sedation and Delirium of the Sociedad Argentina de Terapia Intensiva. RESULTS: Recommendations were agreed upon, and tools were developed to ensure a comprehensive approach to analgesia, sedation, delirium, early mobility and family engagement for adult patients with acute respiratory distress syndrome due to COVID-19. DISCUSSION: Given the new order generated in intensive therapies due to the advancing COVID-19 pandemic, we propose to not leave aside the usual good practices but to adapt them to the particular context generated. Our consensus is supported by scientific evidence and national and international experience and will be an attractive consultation tool in intensive therapies.

OBJETIVO: Proponer estrategias agile para este abordaje integral de la analgesia, sedación, delirium, implementación de movilidad temprana e inclusión familiar del paciente con síndrome de dificultad respiratoria aguda por COVID-19, considerando el alto riesgo de infección que existe entre los trabajadores de salud, el tratamiento humanitario que debemos brindar al paciente y su familia, en un contexto de falta estrategias terapéuticas específicas contra el virus globalmente disponibles a la fecha y una potencial falta de recursos sanitarios. METODOS: Se llevó a cabo una revision no sistemática de la evidencia científica en las principales bases de datos bibliográficos, sumada a la experiencia y juicio clínico nacional e internacional. Finalmente, se realizó un consenso de recomendaciones entre los integrantes del Comité de Analgesia, Sedación y Delirium de la Sociedad Argentina de Terapia Intensiva. RESULTADOS: Se acordaron recomendaciones y se desarrollaron herramientas para asegurar un abordaje integral de analgesia, sedación, delirium, implementación de movilidad temprana e inclusión familiar del paciente adulto con síndrome de dificultad respiratoria aguda por COVID-19. DISCUSIÓN: Ante el nuevo orden generado en las terapias intensivas por la progresión de la pandemia de COVID-19, proponemos no dejar atrás las buenas prácticas habituales, sino adaptarlas al contexto particular generado. Nuestro consenso está respaldado en la evidencia científica, la experiencia nacional e internacional, y será una herramienta de consulta atractiva en las terapias intensivas.

Analgesia and sedation in patients with ARDS.

Acute Respiratory Distress Syndrome (ARDS) is one of the most demanding conditions in an Intensive Care Unit (ICU). Management of analgesia and sedation in ARDS is particularly challenging. An expert panel was convened to produce a "state-of-the-art" article to support clinicians in the optimal management of analgesia/sedation in mechanically ventilated adults with ARDS, including those with COVID-19. Current ICU analgesia/sedation guidelines promote analgesia first and minimization of sedation, wakefulness, delirium prevention and early rehabilitation to facilitate ventilator and ICU liberation. However, these strategies cannot always be applied to patients with ARDS who sometimes require deep sedation and/or paralysis. Patients with severe ARDS may be under-represented in analgesia/sedation studies and currently recommended strategies may not be feasible. With lightened sedation, distress-related symptoms (e.g., pain and discomfort, anxiety, dyspnea) and patient-ventilator asynchrony should be systematically assessed and managed through interprofessional collaboration, prioritizing analgesia and anxiolysis. Adaptation of ventilator settings (e.g., use of a pressure-set mode, spontaneous breathing, sensitive inspiratory trigger) should be systematically considered before additional medications are administered. Managing the mechanical ventilator is of paramount importance to avoid the unnecessary use of deep sedation and/or paralysis. Therefore, applying an "ABCDEF-R" bundle (R = Respiratory-drive-control) may be beneficial in ARDS patients. Further studies are needed, especially regarding the use and long-term effects of fast-offset drugs (e.g., remifentanil, volatile anesthetics) and the electrophysiological assessment of analgesia/sedation (e.g., electroencephalogram devices, heart-rate variability, and video pupillometry). This review is particularly relevant during the COVID-19 pandemic given drug shortages and limited ICU-bed capacity.

Optimal Sedation and Pain Management: A Patient- and Symptom-Oriented Paradigm.

In the critically ill patient, optimal pain and sedation management remains the cornerstone of achieving comfort, safety, and to facilitate complex life support interventions. Pain relief, using multimodal analgesia, is an integral component of any orchestrated approach to achieve clinically appropriate goals in critically ill patients. Sedative management, however, remains a significant challenge. Subsequent studies including most recent randomized trials have failed to provide strong evidence in favor of a sedative agent, a mode of sedation or ancillary protocols such as sedative interruption and sedative minimization. In addition, clinical practice guidelines, despite a comprehensive evaluation of relevant literature, have limitations when applied to individual patients. These limitations have been most apparent during the coronavirus disease 2019 pandemic. As such, there is a need for a mindset shift to a practical and achievable sedation strategy, driven by patients' characteristics and individual patient needs, rather than one cocktail for all patients. In this review, we present key principles to achieve patient-and symptom-oriented optimal analgesia and sedation in the critically ill patients. Sedative intensity should be proportionate to care complexity with due consideration to an individual patient's modifiers. The use of multimodal analgesics, sedatives, and antipsychotics agents-that are easily titratable-reduces the overall quantum of sedatives and opioids, and reduces the risk of adverse events while maximizing clinical benefits. In addition, critical considerations regarding the choice of sedative agents should be given to factors such as age, medical versus operative diagnosis, and cardiovascular status. Specific populations such as trauma, neurological injury, and pregnancy should also be taken into account to maximize efficacy and reduce adverse events.

Guidelines: Anaesthesia in the context of COVID-19 pandemic.

OBJECTIVES: The world is currently facing an unprecedented healthcare crisis caused by the COVID-19 pandemic. The objective of these guidelines is to produce a framework to facilitate the partial and gradual resumption of intervention activity in the context of the COVID-19 pandemic. METHODS: The group has endeavoured to produce a minimum number of recommendations to highlight the strengths to be retained in the 7 predefined areas: (1) protection of staff and patients; (2) benefit/risk and patient information; (3) preoperative assessment and decision on intervention; (4) modalities of the preanaesthesia consultation; (5) specificity of anaesthesia and analgesia; (6) dedicated circuits and (7) containment exit type of interventions. RESULTS: The SFAR Guideline panel provides 51 statements on anaesthesia management in the context of COVID-19 pandemic. After one round of discussion and various amendments, a strong agreement was reached for 100% of the recommendations and algorithms. CONCLUSION: We present suggestions for how the risk of transmission by and to anaesthetists can be minimised and how personal protective equipment policies relate to COVID-19 pandemic context.