Executive Summary of the Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR) Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management.

The Airway section of the Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) present the Guidelines for the integral management of difficult airway in adult patients. This document provides recommendations based on current scientific evidence, theoretical-educational tools and implementation tools, mainly cognitive aids, applicable to the treatment of the airway in the field of anesthesiology, critical care, emergencies and prehospital medicine. Its principles are focused on the human factors, cognitive processes for decision-making in critical situations and optimization in the progression of the application of strategies to preserve adequate alveolar oxygenation in order to improve safety and quality of care.

A new score for airway assessment using clinical and ultrasound parameters.

Background: Over the last few years, ultrasonography has been introduced as the fifth pillar to patient's bedside physical examination. Clinical assessments aim to screen and look for airway difficulties to predict difficult intubations, but none have demonstrated a significant predictive capacity. Recent systematic reviews have established a correlation between ultrasound imaging and difficult direct laryngoscopy. The primary objective of this study was to determine whether the utilization of ultrasonography to examine the upper airway could accurately predict difficult direct laryngoscopy. Methods: This is a prospective observational study including 102 adult patients that required general anesthesia for elective surgery. Preoperatively, clinical airway assessments were performed. Data such as Mallampati-Samsoon grade (MS), upper lip bite test (ULBT), thyromental (TMD) and sternomental distance (SMD), cervical circumference (CC) and the Arné risk index were collected. Ultrasound evaluation was taken at five different levels in two planes, parasagittal and transverse. Therefore, the following measurements were registered: distance from skin to hyoid bone (DSHB), distance from skin to thyrohyoid membrane (DSTHM), distance from skin to epiglottis (DSE), distance from skin to thyroid cartilage (DSTC) and distance from hyoid bone and thyroid cartilage (DHBTC). Patients were divided into two groups based on the difficulty to perform direct laryngoscopy, according to Cormack-Lehane (C-L) classification. Grades I and II were classified as easy laryngoscopy and grades III or IV as difficult. Logistic regression models and the Receiver Operating Characteristic (ROC) curve was employed to determine the diagnostic precision of ultrasound measurements to distinguish difficult laryngoscopy (DL). Results: The following risk score for DL was obtained, DSTHM ≥ 1.60 cm (2 points), DSTC ≥ 0.78 cm (3 points) and gender (2 points for males). The score can range from 0 to 7 points, and showed and AUC (95% CI) of 0.84 (0.74-0.95). A score of 5 points or higher indicates a 34-fold increase in the risk of finding DL (p = 0.0010), sensitivity of 91.67, specificity of 75.56, positive predictive value of 33.33, and negative predictive value of 98.55. Conclusion: The use of ultrasonography combined with classic clinical screening tests are useful tools to predict difficult direct laryngoscopy.

Inhalation anesthesia without any intravenous management for pediatric proton beam therapy.

INTRODUCTION: Proton beam therapy is an oncological treatment, argued to be an appropriate tumor irradiation technique for childhood solid tumors. Due to its duration and the need for immobility, many children require anesthesia for proton therapy sessions. As not many centers in the world provide this therapy, there is little published research about pediatric anesthesia for these cases, and the available data suggest a preference for intravenous anesthesia or combined intravenous and inhalation anesthesia. We conducted this study with the aim of describing and analyzing the inhalation anesthetic management of children undergoing proton therapy at our medical center, comparing our results with studies that have followed different anesthetic protocols. METHODS: We reviewed two major databases (Web of Science and Scopus) to find papers that had addressed, to date, anesthesia for pediatric proton therapy. To describe our anesthetic management, we included all pediatric patients treated with proton therapy under anesthesia in our center between June 2020 and August 2021. The characteristics of the patients, their diagnoses, treatments, airway management, drugs administered, duration of induction, and recovery from anesthesia, and adverse effects where all recorded. All anesthesiologists followed a strict anesthetic protocol based only on inhalational anesthesia with sevoflurane delivered via laryngeal mask airway. RESULTS: Of the total of 1082 papers found in Web of Science and Scopus on pediatric proton therapy, 11 have addressed its anesthetic management, using intravenous or combined intravenous and inhalation anesthesia. Between June 2020 and August 2021, 31 children were anesthetized in our center to receive proton therapy under inhalational anesthesia (total number of sessions: 873). The mean anesthesia induction time was 4.1 min (SD = 0.7, 95% CI [3.9, 4.4]). The mean anesthesia recovery time was 13.8 min (SD = 4.1, 95% CI [12.3, 15.3]). The percentage of non-serious adverse effects was 0.7% (Clopper-Pearson 95% CI [0.3, 1.5]). The percentage of serious adverse effects was 0.1% (Clopper-Pearson 95% CI [0, 0.6]), without statistically significant difference with other published works with different anesthetic approaches. CONCLUSION: Inhalation anesthesia without any intravenous management for pediatric proton therapy is, in our experience, an effective technique with a complication rate similar to other anesthetic approaches.

Preoperative airway ultrasound assessment in the sniffing position: a prospective observational study.

BACKGROUND: Clinical airway screening tests intend to predict difficult airways, but none have a high predictive value. Recent systematic reviews correlate ultrasound with difficult laryngoscopy. This study aimed primarily to correlate ultrasound measurements of anatomical upper airway structures in the sniffing position with difficult direct laryngoscopy. The secondary aim was to observe gender-based differences. METHODS: This prospective, cross-sectional, single-center observational study included 209 patients requiring general anesthesia for elective surgery. Preoperatively, we performed six clinical airway assessments and three ultrasound measurements, which were the Distance from Skin to the Hyoid Bone (DSHB), to the Epiglottis (DSE), and to the anterior commissure of the vocal cords (DSAC) in a sniffing position. Benumof's criteria for the "best view at the first attempt" for direct laryngoscopy assessed the difficulty of laryngoscopy. RESULTS: The distance from skin to the epiglottis was the best predictor of direct difficult laryngoscopy (defined as Cormack-Lehane grade ≥ 2b) with a minimum thickness cut-off at 2.70 ± 0.19 cm (sensitivity 91.3%; specificity 96.9%). The skin to the hyoid bone distance cut-off was 1.41 ± 0.30 cm with moderate correlation (sensitivity 80.4%; specificity 60.1%). No correlation was found for the distance to the anterior commissure of the vocal cords. In women compared to men, the skin to the epiglottis distance was more sensitive (92.3% vs. 90.9%) and specific (98.8% vs. 95.2%). CONCLUSIONS: DSE in the sniffing position is the most reliable parameter for preoperative airway ultrasound assessment in the Caucasian population, with higher sensitivity and specificity in women, and might be considered as an independent predictor for direct difficult laryngoscopy.

Preoperative airway ultrasound assessment in the sniffing position: a prospective observational study

Abstract Background: Clinical airway screening tests intend to predict difficult airways, but none have a high predictive value. Recent systematic reviews correlate ultrasound with difficult laryngoscopy. This study aimed primarily to correlate ultrasound measurements of anatomical upper airway structures in the sniffing position with difficult direct laryngoscopy. The secondary aim was to observe gender-based differences. Methods: This prospective, cross-sectional, single-center observational study included 209 patients requiring general anesthesia for elective surgery. Preoperatively, we performed six clinical airway assessments and three ultrasound measurements, which were the Distance from Skin to the Hyoid Bone (DSHB), to the Epiglottis (DSE), and to the anterior commissure of the vocal cords (DSAC) in a sniffing position. Benumof's criteria for the "best view at the first attempt" for direct laryngoscopy assessed the difficulty of laryngoscopy. Results: The distance from skin to the epiglottis was the best predictor of direct difficult laryngoscopy (defined as Cormack-Lehane grade > 2b) with a minimum thickness cut-off at 2.70 ± 0.19 cm (sensitivity 91.3%; specificity 96.9%). The skin to the hyoid bone distance cut-off was 1.41 ± 0.30 cm with moderate correlation (sensitivity 80.4%; specificity 60.1%). No correlation was found for the distance to the anterior commissure of the vocal cords. In women compared to men, the skin to the epiglottis distance was more sensitive (92.3% vs. 90.9%) and specific (98.8% vs. 95.2%). Conclusions: DSE in the sniffing position is the most reliable parameter for preoperative airway ultrasound assessment in the Caucasian population, with higher sensitivity and specificity in women, and might be considered as an independent predictor for direct difficult laryngoscopy.

Identifying SARS-CoV-2 'memory' NK cells from COVID-19 convalescent donors for adoptive cell therapy.

COVID-19 disease is the manifestation of syndrome coronavirus 2 (SARS-CoV-2) infection, which is causing a worldwide pandemic. This disease can lead to multiple and different symptoms, being lymphopenia associated with severity one of the most persistent. Natural killer cells (NK cells) are part of the innate immune system, being fighting against virus-infected cells one of their key roles. In this study, we determined the phenotype of NK cells after COVID-19 and the main characteristic of SARS-CoV-2-specific-like NK population in the blood of convalescent donors. CD57+ NKG2C+ phenotype in SARS-CoV-2 convalescent donors indicates the presence of 'memory'/activated NK cells as it has been shown for cytomegalovirus infections. Although the existence of this population is donor dependent, its expression may be crucial for the specific response against SARS-CoV-2, so that, it gives us a tool for selecting the best donors to produce off-the-shelf living drug for cell therapy to treat COVID-19 patients under the RELEASE clinical trial (NCT04578210).

Ecografía de vía aérea: en busca de la membrana cricotiroidea / Airway ultrasound: in search of the cricothyoid membrane

Resumen: La ecografía forma parte activa de las herramientas clínicas que tenemos en nuestro arsenal para la valoración de pacientes, y en el manejo de la vía aérea puede permitirnos localizar y marcar la membrana cricotiroidea previo al manejo de un paciente con posible vía aérea difícil (VAD). En manos adiestradas permite identificar la anatomía para poder realizar una cricotiroidotomía con rapidez y precisión en tan sólo 24.3 segundos. En este artículo se muestra una sistemática visual y de rápida localización ecográfica de la membrana cricotiroidea con tiempo estimado inferior a un minuto. Para la exploración se debe usar una sonda lineal de alta frecuencia (5-14 MHz), ya que es probablemente la más adecuada para evaluar estructuras superficiales (dentro de 0-5 cm por debajo de la superficie de la piel). La colocación del operador y del ecógrafo van a depender de la posición del paciente, así en pacientes sentados el operador se coloca detrás de éste y el ecógrafo enfrente de ambos, y en pacientes en decúbito supino el operador se coloca a la cabecera del paciente y el ecógrafo a nivel del codo derecho del mismo.

Abstract: Ultrasonography is an active part of the clinical tools that we have in our arsenal for the evaluation of patients, and in the management of the airway, it can allow us to locate and mark the cricothyroid membrane prior to the management of a patient with a possible Difficult Airway. In trained hands allows the anatomy to be identified so that a cricothyroidotomy can be performed quickly and accurately in just 24.3 seconds. In this article, we show a rapid and visual systematic ultrasound localization of the cricothyroid membrane with an estimated time less than one minute. A linear high-frequency probe (5-14 MHz) should be used for exploration, as it is probably the most suitable for evaluating surface structures (within 0-5 cm below the skin surface). The positioning of the operator and the ultrasound scanner will depend on the patient's position, so in seated patients the operator is placed behind him and the ultrasound scanner in front of both, and in patients in a supine position, the operator is placed at the bedside of the patient and the ultrasound at the level of the right elbow.

Impact of implementing pathogen reduction technologies for platelets on reducing outdates.

BACKGROUND AND OBJECTIVES: Applying pathogen reduction technologies (PRT) to platelets can extend their shelf life from 5 to 7 days, but there have been few systematic studies of the repercussions of such technologies on outdate rates. MATERIAL AND METHODS: The benefits in terms of outdate rates of applying PRT to platelets are studied via a mathematical simulation. Specifically, statistical methods are used to determine the daily production rate needed to meet demand while not exceeding a maximum amount set as a result of limitations on donations and while assuring a minimum daily stock. RESULTS: The results show that a 2-day extension in the shelf life of platelet concentrates (PC) results in reductions in outdates ranging from 88·4% to 100% at the production centres analysed. It may be the case for budgetary reasons that only part of the PCs produced can be treated. This being so, we show that if the proportion treated per annum exceeds 25% the best option is to treat part of the output every day, otherwise, it is preferable to concentrate treatment on the last two production days of the week. CONCLUSIONS: Extending the shelf life of PC from five to seven days and setting up suitable production logistics can drastically reduce outdates at production centres. If only a part of all PCs is treated, the best choices are to distribute PRT overall production days or, if the percentage of PCs treated is very low, to apply PRT on the days preceding the weekend break.

Analysis of the Spanish CCR5-∆32 inventory of cord blood units: lower cell counts in homozygous donors.

The possibility to use CCR5-∆32 umbilical cord blood to cure HIV infection in patients in need of a hematopoietic transplant has been suggested. The less stringent HLA compatibility needed in this type of transplant facilitates the search of a suitable donor having the CCR5-∆32 mutation. To achieve an inventory of CCR5-∆32 cord blood units, the 20,236 best cell quality units of the Spanish Registry were genotyped. Furthermore, their CD34+ and total nucleated cells counts, blood type, gender, HLA and donor's geographical and ancestral origin were analyzed. The results showed 130 (0.64%) units homozygous for the deletion, 2,646 (13.08%) heterozygous and 17,460 (86.28%) did not present the mutation. Interestingly, a significant lower amount of CD34+ cells was found in the CCR5-∆32 homozygous units. In addition, a significant association was found among donor's ancestral origin and the mutation, with a higher percentage of CCR5-∆32 units with a European ancestry. In summary, identification of a relatively high number of CCR5-∆32 units is feasible and will facilitate the development of clinical trials for HIV cure in patients requiring hematopoietic transplantation. Further studies are required to understand the significance of lower cell counts within the CCR5-∆32 homozygous group and its clinical impact.

Nitric oxide increases cardiac IK1 by nitrosylation of cysteine 76 of Kir2.1 channels.

RATIONALE: The cardiac inwardly rectifying K(+) current (I(K1)) plays a critical role in modulating excitability by setting the resting membrane potential and shaping phase 3 of the cardiac action potential. OBJECTIVE: This study aims to analyze the effects of nitric oxide (NO) on human atrial I(K1) and on Kir2.1 channels, the major isoform of inwardly rectifying channels present in the human heart. METHODS AND RESULTS: Currents were recorded in enzymatically isolated myocytes and in transiently transfected CHO cells, respectively. NO at myocardial physiological concentrations (25 to 500 nmol/L) increased inward and outward I(K1) and I(Kir2.1). These effects were accompanied by hyperpolarization of the resting membrane potential and a shortening of the duration of phase 3 of the human atrial action potential. The I(Kir2.1) increase was attributable to an increase in the open probability of the channel. Site-directed mutagenesis analysis demonstrated that NO effects were mediated by the selective S-nitrosylation of Kir2.1 Cys76 residue. Single ion monitoring experiments performed by liquid chromatography/tandem mass spectrometry suggested that the primary sequence that surrounds Cys76 determines its selective S-nitrosylation. Chronic atrial fibrillation, which produces a decrease in NO bioavailability, decreased the S-nitrosylation of Kir2.1 channels in human atrial samples as demonstrated by a biotin-switch assay, followed by Western blot. CONCLUSIONS: The results demonstrated that, under physiological conditions, NO regulates human cardiac I(K1) through a redox-related process.

Nitric oxide inhibits Kv4.3 and human cardiac transient outward potassium current (Ito1).

AIMS: Chronic atrial fibrillation (CAF) is characterized by a shortening of the plateau phase of the action potentials (AP) and a decrease in the bioavailability of nitric oxide (NO). In this study, we analysed the effects of NO on Kv4.3 (I(Kv4.3)) and on human transient outward K(+) (I(to1)) currents as well as the signalling pathways responsible for them. We also analysed the expression of NO synthase 3 (NOS3) in patients with CAF. METHODS AND RESULTS: I(Kv4.3) and I(to1) currents were recorded in Chinese hamster ovary cells and in human atrial and mouse ventricular dissociated myocytes using the whole-cell patch clamp. The expression of NOS3 was analysed by western blotting. AP were recorded using conventional microelectrode techniques in mouse atrial preparations. NO and NO donors inhibited I(Kv4.3) and human I(to1) in a concentration- and voltage-dependent manner (IC(50) for NO: 375.0 +/- 48 nM) as a consequence of the activation of adenylate cyclase and the subsequent activation of the cAMP-dependent protein kinase and the serine-threonine phosphatase 2A. The density of the I(to1) recorded in ventricular myocytes from wild-type (WT) and NOS3-deficient mice (NOS3(-/-)) was not significantly different. Furthermore, the duration of atrial AP repolarization in WT and NOS3(-/-) mice was not different. The increase in NO levels to 200 nM prolonged the plateau phase of the mouse atrial AP and lengthened the AP duration measured at 20 and 50% of repolarization of the human atrial CAF-remodelled AP as determined using a mathematical model. However, the expression of NOS3 was not modified in left atrial appendages from CAF patients. CONCLUSION: Our results suggested that the increase in the atrial NO bioavailability could partially restore the duration of the plateau phase of CAF-remodelled AP by inhibiting the I(to1) as a result of the activation of non-canonical enzymatic pathways.

Cardiac fibrillation: from ion channels to rotors in the human heart.

Recent new information on the dynamics and molecular mechanisms of electrical rotors and spiral waves has increased our understanding of both atrial fibrillation and ventricular fibrillation. In this brief review, we evaluate the available evidence for the separate roles played by individual sarcolemmal ion channels in atrial fibrillation and ventricular fibrillation, assessing the clinical relevance of such findings. Importantly, although human data support the idea that rotors are a crucial mechanism for fibrillation maintenance in both atria and ventricles, there are clear inherent differences between the 2 chamber types, particularly in regard to the role of specific ion channels in fibrillation. But there also are similarities. This knowledge, together with new information on the changes that take place during disease evolution and between structurally normal and diseased hearts, may enhance our understanding of fibrillatory processes pointing to new approaches to improve disease outcomes.

Lipid-lowering therapy with statins, a new approach to antiarrhythmic therapy.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (statins) are the most effective and best-tolerated drugs to treat elevated levels of low-density lipoprotein cholesterol (LDL-C). In addition, they exhibit other effects unrelated to their lipid lowering effects (pleiotropic actions). In recent years, experimental and clinical evidence demonstrates that statins exert antiarrhythmic properties, reducing the recurrences of supraventricular and life-threatening ventricular arrhythmias both in patients with and without coronary artery disease (CAD). Thus, statins may constitute a novel therapeutic approach to cardiac arrhythmias. This article reviews the antiarrhythmic properties of statins as well as the possible mechanisms involved, including the lowering of LDL-C levels, the improvement of endothelial dysfunction and autonomic function, the stabilization of the atherosclerotic plaques, the antioxidant, antiinflammatory, antithrombotic and cardioprotective properties and the modulation of transmembrane ion fluxes.

Genetically engineered mice as a model for studying cardiac arrhythmias.

Sudden cardiac death due to ventricular tachyarrhythmias remains an unresolved problem, probably because the mechanisms responsible for the progression of cardiac disease to electrophysiological failure are poorly understood. Genetically engineered mice, the principal mammalian model for studying cardiac electrophysiology, have contributed to the understanding of the genetic, molecular and systemic mechanisms involved in the initiation and/or maintenance of cardiac arrhythmias leading to cardiac death, e.g. cardiac excitability, conduction velocity and refractoriness. Several murine models harbouring human gene mutations leading to electrical and structural cardiac disorders have been developed, including channelopathies (long QT syndrome), familial conduction disorders, cardiomyopathies and other inherited cardiac disorders. This article reviews the results of the main genetically modified mice addressing the genesis of cardiac arrhythmias and sudden cardiac death.

Ivabradina, un bloqueador selectivo de la corriente If. Aspectos farmacológicos y tolerabilidad / Ivabradine: a selective If current inhibitor. Pharmacological characteristics and tolerability

La frecuencia cardiaca es el principal determinante de las demandas miocárdicas de O2 y del flujo sanguíneo coronario. La frecuencia cardiaca depende de la actividad eléctrica espontánea de las células marcapasos del nódulo sinoauricular. Estas células presentan una fase de despolarización diastólica que desplaza el potencial de membrana hacia su valor umbral y se inicia un nuevo potencial de acción que se propaga a través del miocardio y produce una respuesta contráctil. La corriente If de entrada de iones Na+ y K+ a través de canales activados por la hiperpolarización y modulados por nucleótidos cíclicos (HCN) es la principal determinante de la inclinación de la fase de lenta despolarización diastólica. Los canales se abren cuando el potencial de membrana se hiperpolariza y se modulan por la concentración celular de adenosinmonofosfato cíclico. La ivabradina es un bloqueador específico de la If. Para ello debe atravesar la membrana y alcanzar su receptor, que se encuentra en la boca intracelular del poro del canal. Como consecuencia, produce una reducción dependiente de la dosis de la frecuencia cardiaca, que reduce las demandas miocárdicas de O2 y aumenta el flujo sanguíneo coronario. Sin embargo, a concentraciones terapéuticas no inhibe otras corrientes iónicas cardiacas, razón por la que no modifica la presión arterial, la contractilidad o las propiedades electrofisiológicas cardiacas. En este artículo se revisa el mecanismo de acción, las propiedades farmacocinéticas y farmacodinámicas y las reacciones adversas y contraindicaciones de la ivabradina (AU)

The heart rate is the main determinant of both myocardial oxygen demand and coronary blood flow. Heart rate is determined by spontaneous electrical activity in the pacemaker cells of the sinoatrial node. These cells exhibit a diastolic depolarization phase that drives the membrane potential towards the threshold value for initiating a new action potential, which propagates throughout the myocardium and triggers a contractile response. The If current, an inward current of Na+ and K+ ions through hyperpolarization- activated cyclic-nucleotide-gated (HCN) channels, is the main determinant of the slope of the slow diastolic depolarization phase. These channels open in response to membrane hyperpolarization and are modulated by the intracellular cAMP concentration. Ivabradine specifically blocks the If current. To do so, it crosses the membrane and binds to a receptor located on the intracellular side of the channel pore. As a result, ivabradine produces a dose-dependent decrease in heart rate that reduces myocardial oxygen demand and increases coronary blood flow. However, at therapeutic concentrations, it does not affect other cardiac ionic currents, which is why ivabradine does not alter blood pressure, cardiac contractility, or cardiac electrophysiological parameters. This article reviews ivabradine’s mechanism of action, pharmacodynamic and pharmacokinetic properties, side effects, and interactions (AU)