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.

Use of Transesophageal Echocardiography During Orthotopic Liver Transplantation: Simplifying the Procedure.

The intraoperative management of patients undergoing orthotopic liver transplantation (OLT) is influenced by the cardiovascular manifestations typically found in the context of end-stage liver disease, by the presence of concomitant cardiovascular disease, and by the significant hemodynamic changes that occur during surgery. Hypotension and intraoperative blood pressure fluctuations during OLT are associated with liver graft dysfunction, acute kidney failure, and increased risk of 30-d mortality. Patients also frequently present hemodynamic instability due to various causes, including cardiac arrest. Recent evidence has shown transesophageal echocardiography (TEE) to be a useful minimally invasive monitoring tool in patients undergoing OLT that gives valuable real-time information on biventricular function and volume status and can help to detect OLT-specific complications or situations. TEE also facilitates rapid diagnosis of life-threatening conditions in each stage of OLT, which is difficult to identify with other types of monitoring commonly used. Although there is no consensus on the best approach to intraoperative monitoring in these patients, intraoperative TEE is safe and useful and should be recommended during OLT, according to experts, for assessing hemodynamic changes, identifying possible complications, and guiding treatment with fluids and inotropes to achieve optimal patient care.

Clinical impact of del Nido cardioplegia in adult cardiac surgery: A prospective randomized trial.

OBJECTIVE: The study objective was to assess the benefits of del Nido cardioplegia compared with cold blood cardioplegia solution in terms of myocardial protection during adult cardiac surgery. METHODS: A total of 474 adult patients undergoing coronary artery bypass grafting, heart valve surgery, thoracic aortic surgery, or combined procedures were randomized to the del Nido cardioplegia group (n = 234) or the cold blood cardioplegia solution group (n = 240) after provided informed consent. The primary end points assessed inotropic support requirements, severe cardiovascular events, and troponin trend within the first 48 hours of intensive care unit stay. Reperfusion arrhythmias, aortic crossclamp and cardiopulmonary bypass times, and other clinical perioperative variables were considered as secondary end points. RESULTS: No statistically significant differences were found regarding postoperative inotropic support requirements or the incidence of severe cardiovascular events. The del Nido cardioplegia group showed a higher return to spontaneous sinus rhythm (P< .001), a lower number of defibrillation attempts (P< .001), and an earlier peak troponin value in the postoperative period. Peak blood glucose levels and intravenous insulin requirements were significantly lower in the del Nido cardioplegia group. We found no significant differences regarding aortic crossclamp or cardiopulmonary bypass time. We did observe a lower incidence of postoperative stroke in the del Nido cardioplegia group (2.6% vs 6.7%; P= .035). CONCLUSIONS: del Nido cardioplegia can be used safely and with comparable outcomes compared with traditional cardioplegia solutions. Additional advantages over glycemic control, reperfusion arrhythmias, and its comfortable redosing interval make del Nido an interesting alternative for myocardial protection in adult cardiac surgery. A significant decrease in postoperative stroke will require further research to shed light on the results of this study. VIDEO ABSTRACT.

Individualizing mechanical ventilation: titration of driving pressure to pulmonary elastance through Young's modulus in an acute respiratory distress syndrome animal model.

BACKGROUND: Mechanical ventilation increases the risk of lung injury (VILI). Some authors propose that the way to reduce VILI is to find the threshold of driving pressure below which VILI is minimized. In this study, we propose a method to titrate the driving pressure to pulmonary elastance in an acute respiratory distress syndrome model using Young's modulus and its consequences on ventilatory-induced lung injury. MATERIAL AND METHODS: 20 Wistar Han male rats were used. After generating an acute respiratory distress syndrome, two groups were studied: (a) standard protective mechanical ventilation: 10 rats received 150 min of mechanical ventilation with driving pressure = 14 cm H2O, tidal volume < 6 mL/kg) and (b) individualized mechanical ventilation: 10 rats received 150 min of mechanical ventilation with an individualized driving pressure according to their Young's modulus. In both groups, an individualized PEEP was programmed in the same manner. We analyzed the concentration of IL-6, TNF-α, and IL-1ß in BAL and the acute lung injury score in lung tissue postmortem. RESULTS: Global driving pressure was different between the groups (14 vs 11 cm H2O, p = 0.03). The individualized mechanical ventilation group had lower concentrations in bronchoalveolar lavage of IL-6 (270 pg/mL vs 155 pg/mL, p = 0.02), TNF-α (292 pg/mL vs 139 pg/mL, p < 0.01) and IL-1ß (563 pg/mL vs 131 pg/mL, p = 0.05). They presented lower proportion of lymphocytes (96% vs 79%, p = 0.05) as well as lower lung injury score (6.0 points vs 2.0 points, p = 0.02). CONCLUSION: In our model, individualization of DP to pulmonary elastance through Young's modulus decreases lung inflammation and structural lung injury without a significant impact on oxygenation.

Critical Care in SARS-CoV-2 Infected Pregnant Women: A Prospective Multicenter Study.

Evidence suggests that pregnant women are at a higher risk of complications compared to the general population when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the reasons that lead them to need intensive care are not clear. This is a prospective multicenter study of SARS-CoV-2 positive pregnant women, registered by the Spanish Obstetric Emergency Group, with the objective to define the characteristics of the mothers who were admitted to the Intensive Care Unit (ICU) and to investigate the causes and risk factors for ICU admission. A total of 1347 infected pregnant women were registered and analyzed, of whom, 35 (2.6%) were admitted to the ICU. No differences in maternal characteristics or comorbidities were observed between ICU and non-ICU patients, except for in vitro fertilization and multiple pregnancies. The main causes of admission to the ICU were non-obstetric causes (worsening of the maternal condition and respiratory failure due to SARS-CoV-2 pneumonia, 40%) and a combination of coronavirus disease 2019 (COVID-19) symptoms and obstetrical complications (31.4%). The multivariable logistic analysis confirmed a higher risk of ICU admission when pre-eclampsia or hemorrhagic events coexist with pneumonia. The incidence of thromboembolic events and disseminated intravascular coagulation were also significantly higher among patients admitted to the ICU. Therefore, surveillance and rapid intervention should be intensified in SARS-CoV-2 infected pregnant women with the mentioned risk factors and complications. Emphasis should always be placed on anticoagulant therapy in these patients due to the increased thromboembolic risk, C-section surgery and immobilization in the ICU.

Del Nido Cardioplegia Versus Cold Blood Cardioplegia in Adult Cardiac Surgery: Protocol for a Randomized Controlled Trial.

BACKGROUND: The use of cardioplegia solutions as a myocardial protection technique is essential during cardiac surgery with cardiopulmonary bypass. The del Nido cardioplegia solution (DNS) has been widely used as a myocardial preservation technique for pediatric patients undergoing cardiac surgery with cardiopulmonary bypass. Its unique pharmacological features have created growing interest for adult cardiac surgery, especially for elderly patients or those with ventricular dysfunction who are more prone to ischemia-reperfusion injury. Ever since its implementation, several retrospective studies have been published to validate the efficacy, safety, and efficiency of DNS in adult patients undergoing coronary revascularization, valve replacement, or combined procedures. Recently, a meta-analysis based on nine retrospective studies was published claiming the noninferiority of DNS compared to other conventional cardioplegia solutions. Few prospective randomized studies have been conducted whose primary outcome was the assessment of DNS clinical efficacy compared to other solutions commonly used in adult patients. OBJECTIVE: The aim of this randomized clinical trial is to assess the benefits of DNS compared to Cardi-Braun blood cardioplegia solution in clinical and biochemical terms regarding myocardial protection during adult cardiac surgery. METHODS: This is the protocol of a controlled, randomized, single-center clinical trial carried out at the Puerta de Hierro Majadahonda University Hospital in Spain. A total of 474 participants over the age of 18 years undergoing elective cardiac surgery with cardiopulmonary bypass will be assigned to groups by simple randomization to receive either DNS or Cardi-Braun blood cardioplegia solution. The primary outcome will be the differences between groups in myocardial protection in biochemical terms (ie, perioperative troponin levels) and clinical terms (ie, presence of the composite variable acute cardiovascular event). The clinical trial will be carried out under conditions of respect for the fundamental rights of the person and the ethical principles that affect biomedical research with human beings, as well as in accordance with international recommendations contained in the Declaration of Helsinki and its subsequent revisions. RESULTS: The inclusion process started in 2018. Data cleaning and analyses are expected to take place in the fall of 2020 and the results are expected in January 2021. CONCLUSIONS: This study is particularly relevant as it will be one of the first to analyze the clinical effects of del Nido cardioplegia on the basis of direct myocardial protection parameters. In light of published studies, carrying out prospective studies based on primary clinical objectives with a larger sample, high-risk patients, and longer cardiopulmonary bypass times continues to be necessary. We believe that our study addresses an important gap in the knowledge of del Nido cardioplegia in adult patient cardiac surgery and will be able to clarify the possible benefits of this method in a large population of patients undergoing these procedures. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2017-005144-14; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2017-005144-14+; ClinicalTrials.gov NCT04094168; https://clinicaltrials.gov/ct2/show/NCT04094168. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17826.

Novel auristatin E-based albumin-binding prodrugs with superior anticancer efficacy in vivo compared to the parent compound.

Auristatins are a class of highly cytotoxic tubulin-disrupting peptides, which have shown limited therapeutic effect as free agents in clinical trials. In our continuing effort to develop acid-sensitive albumin-binding anticancer drugs exploiting circulating serum albumin as the drug carrier, we investigated the highly toxic drug payload auristatin E to assess whether the corresponding albumin-binding prodrugs were a viable option for achieving significant and concomitant tolerable antitumor activity. To achieve our goal, we developed a new aromatic maleimide-bearing linker (Sulf07) which enhanced both water solubility and stability of the prodrugs. In this study, we describe two auristatin E-based albumin-binding drugs, AE-Keto-Sulf07 and AE-Ester-Sulf07, which were designed to release the active compound at the tumor site in a pH-dependent manner. These prodrugs incorporate an acid-sensitive hydrazone bond, formed by the reaction of a carbonyl-containing auristatin E derivative with the hydrazide group of the water-solubilizing maleimide-bearing linker Sulf07. A panel of patient- and cell-derived human tumor xenograft models (melanoma A375, ovarian carcinoma A2780, non-small-cell lung cancer LXFA737 and LXFE937, and head and neck squamous cell carcinomas) were screened with starting tumor volumes in the range of either 130-150 mm3 (small tumors) or 270-380 mm3 (large tumors). Both albumin-binding prodrugs showed compelling anticancer efficacy compared to the parent drug auristatin E, inducing statistically significant long-term partial and/or complete tumor regressions. AE-Keto-Sulf07 displayed very good antitumor response over a wide dose range, 3.0-6.5 mg/kg (5-8 injections, biweekly). AE-Ester-Sulf07 was highly efficacious between 1.9 and 2.4 mg/kg (8 injections, biweekly) or at 3.8 mg/kg (4 injections, weekly), but caused cumulative skin irritation due to scratching and biting. In contrast at its MTD, auristatin E (0.3 mg/kg, 8 injections, biweekly) was only marginally active. In summary, AE-Keto-Sulf07 and AE-Ester-Sulf07 are novel acid-sensitive albumin-binding prodrugs demonstrating tumor regressions in all of the evaluated human tumor xenograft models thus supporting the stratagem that albumin can be used as an effective drug carrier for the highly potent class of auristatins.

Tramadol-induced hyperalgesia and its prevention by ketamine in rats: A randomised experimental study.

BACKGROUND: Opioid analgesia not only reduces inhalational anaesthetic requirements but may also induce delayed hyperalgesia, with potential effects on the minimum alveolar concentration (MAC) of inhalational anaesthetics. OBJECTIVES: The objective of this study was to evaluate the development of tramadol-induced hyperalgesia and the associated changes in MAC, and whether ketamine prevents both processes. DESIGN: A randomised, experimental study. SETTING: Experimental Surgery Unit, La Paz University Hospital, Madrid, Spain. ANIMALS: Thirty-nine adult male Wistar rats. INTERVENTIONS: Mechanical nociceptive thresholds (MNT) were determined up to 21 days after the intraperitoneal administration of a single dose of tramadol (50 mg kg) with or without ketamine (10 mg kg), or 0.9% saline. The MNT and the MAC of sevoflurane were also assessed in a second experiment before, early (30 min) and 7 days after drug administration with the same treatments. MAIN OUTCOME MEASURES: The MAC and MNT were evaluated. The analysis of variance (ANOVA) test was employed to determine differences between treatments and times on MAC and MNT. RESULTS: Tramadol, alone or combined with ketamine, produced an early increase in MNT. However, tramadol given alone decreased MNT from day 1 up to 3 weeks, which was associated with an increase in the MAC of sevoflurane (P < 0.05; day 7). Ketamine administration prevented both the reduction in MNT and the increase in MAC (P > 0.05). CONCLUSION: Tramadol-induced hyperalgesia in the rat lasted for several weeks and was associated with an increase in the MAC of sevoflurane. Prior administration of ketamine blocked both phenomena.

Hyperalgesia and increased sevoflurane minimum alveolar concentration induced by opioids in the rat: a randomised experimental study.

BACKGROUND: Perioperative opioids reduce inhalational anaesthetic requirements. The initial hypoalgesia may, however, be followed by a rebound hyperalgesia. OBJECTIVES: To determine whether prior opioid administration influences inhalational anaesthetic requirements, which might be associated with opioid-induced hyperalgesia. DESIGN: A prospective, randomised, experimental study. SETTING: Experimental Surgery, La Paz University Hospital, Madrid, Spain. ANIMALS: Seventy-nine adult male Wistar rats. INTERVENTIONS: Sevoflurane minimum alveolar concentration (MAC) and mechanical nociceptive thresholds (MNTs) were assessed at baseline and 7 days later following opioid treatment with remifentanil 120 µg  kg-1  h-1, buprenorphine 150 µg kg-1, methadone 8 mg  kg-1 or morphine 10 mg  kg-1 The duration of the effect of remifentanil on MAC and MNT was evaluated in addition to the preventive effect of ketamine 10 mg  kg-1 on remifentanil-induced hyperalgesia. MAIN OUTCOME MEASURES: The effect of different opioid treatments on MAC and MNT was evaluated using analysis of variance (ANOVA). RESULTS: All studied opioids produced an immediate reduction in sevoflurane MAC, followed by an increase (16%) in baseline MAC 7 days later (P < 0.05), although the immediate MAC reduction produced by these opioids at that time was not different. Remifentanil produced a decrease in MNT (P < 0.05), which was associated with an increase in the MAC (P < 0.05) that persisted at 21 days. The effect of remifentanil on MNT and MAC was blocked by ketamine. CONCLUSION: Opioid-induced hyperalgesia was associated with an increase in the MAC in normal rats who had not undergone surgery. Both effects lasted 21 days and were prevented by ketamine.

[Invasive candidiasis in a lung retransplantation recipient]. / Candidiasis invasora en una paciente sometida a retrasplante unipulmonar.

BACKGROUND: Lung-graft loss is a potential problem for the majority of lung-transplant recipients. Retransplantation could be a treatment option, despite significant morbidity and mortality due to infectious complications. The epidemiology, clinical presentation and early treatment are still the basis of the overall approach to the fungal invasive infection after repeated transplant. CLINICAL CASE: This is the case of a 29 year-old woman who underwent a left lung retransplantation due to bronchiolitis obliterans syndrome and developed Candida albicans invasive disease. She received the usual prophylaxis with nebulized liposomal amphotericin B and was also treated with anidulafungin. She received corticosteroid therapy and plasma exchange as acute lung transplant rejection was suspected with subsequent progressive deterioration and death. In the culture of blood samples yeasts were isolated, later identified as C. albicans resistant to fluconazole, caspofungin and micafungin (MCI 128 µg/ml, 8 µg/ml, 4 µg/ml, respectively) and susceptible to anidulafungin and amphotericin B (MCI 0.25 µg/ml, 0.5 µg/ml, respectively). CONCLUSIONS: The empirical management of acute transplant rejection with corticosteroid boluses and plasma exchange can help to spread the underlying and undiagnosed fungal infection. It is considered that an increase in the regular dose of anidulafungin is necessary after plasma exchange. To date, fungal echinocandin resistance did not seem to be a major cause for concern in the treatment of patients with invasive mycoses. However, there is increasing evidence of natural and acquired resistance resulting in life-threatening infections and clinical failure.

Adaptive support ventilation for gynaecological laparoscopic surgery in Trendelenburg position: bringing ICU modes of mechanical ventilation to the operating room.

BACKGROUND AND OBJECTIVE: The aim of the present study was to test the efficacy of adaptive support ventilation (ASV) to automatically adapt the ventilatory settings to the changes in the respiratory mechanics that occur during pneumoperitoneum and Trendelenburg position in gynaecological surgeries. METHODS: We prospectively studied 22 ASA I women scheduled for gynaecological laparoscopic surgery in the Trendelenburg position. After intravenous induction of general anaesthesia, patients were ventilated with ASV, a closed-loop mode of mechanical ventilation based on the Otis formula, designed to automatically adapt the ventilatory settings to changes in the patient's respiratory system mechanics, while maintaining preset minute ventilation. Respiratory mechanics variables, ventilatory setting parameters and analysis of blood gases were recorded at three time points: 5 min after induction (baseline), 15 min after pneumoperitoneum and Trendelenburg positioning (Pneumo-Trend) and 15 min after pneumoperitoneum withdrawal (final). RESULTS: A reduction of 44.4% in respiratory compliance and an increase of 29.1% in airway resistance were observed during the Pneumo-Trend period. Despite these changes in respiratory mechanics, minute ventilation was kept constant. ASV adapted the ventilatory settings by automatically increasing inspiratory pressure by 3.2 +/- 0.9 cmH(2)O (+19%), P < 0.01, respiratory rate by 1.3 +/- 0.5 breaths per minute (+9%) and the inspiratory to total time ratio (T(i)/T(tot)) by 43.3%. At final time, these parameters returned towards their baseline values. Adequate gas exchange was maintained throughout all periods. PaCO(2) increased moderately (+13%) from 4.4 +/- 0.6 (baseline) to 5.0 +/- 0.9 kPa (Pneumo-Trend), P < 0.01; and decreased slightly at final time (4.7 +/- 0.8 kPa), P < 0.05. Clinician's intervention was needed in only one patient who showed a moderate hypercapnia (PaCO(2) 6.9 kPa) during pneumoperitoneum. CONCLUSION: In healthy women undergoing gynaecologic laparoscopy, ASV automatically adapted the ventilatory settings to the changes in the respiratory mechanics, keeping constant the preset minute ventilation, providing an adequate exchange of respiratory gases and obviating clinician's interventions.

Programming pressure support ventilation in pediatric patients in ambulatory surgery with a laryngeal mask airway.

BACKGROUND: Anesthesia workstations with pressure support ventilation (PSV) are available, but there are few studies published on how to program flow-triggered PSV using a laryngeal mask airway (LMA) under general anesthesia in pediatric patients. METHODS: We studied 60 ASA I and II patients, from 2 mo to 14 yr, scheduled for ambulatory surgery under combined general and regional anesthesia with a LMA. Patients were classified according to their body weight as follows: Group A < or =10 kg, Group B 11-20 kg, and Group C >20 kg. All were ventilated in PSV using the following settings: positive end-expiratory pressure of 4 cm H2O, the minimum flow-trigger without provoking auto-triggering, and the minimum level of pressure support to obtain 10 mL/kg of tidal volume. RESULTS: The flow-trigger most frequently used in our study was 0.4 L/min, ranging from 0.2 to 0.6 L/min. We found no correlation between the flow-trigger setting and the patient's age, weight, compliance, resistance, or respiratory rate. There was a good correlation between the level of pressure support (Group A = 15 cm H2O, Group B = 10 cm H2O and Group C = 9 cm H2O) and age (P < 0.001), weight (P < 0.001), dynamic compliance (P < 0.001), and airway resistances (P < 0.001). CONCLUSIONS: PSV with a Proseal LMA in outpatient pediatric anesthesia can be programmed simply using the common clinical noninvasive variables studied. However, more studies are needed to estimate the level of pressure support that may be required in other clinical situations (respiratory pathology, endotracheal tubes, or other types of surgeries) or with other anesthesia workstations.

Anesthetic management of a patient with MERRF syndrome.

There are several specific considerations regarding anesthesia in patients with mitochondrial disease. We describe the successful administration of a combined general and epidural anesthesia with sevoflurane maintenance in a patient with myoclonic epilepsy with ragged red fibers (MERRF syndrome) scheduled for surgical treatment of bilateral clubfoot.