Sedation with Sevoflurane versus Propofol in COVID-19 Patients with Acute Respiratory Distress Syndrome: Results from a Randomized Clinical Trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) related to COVID-19 (coronavirus disease 2019) led to intensive care units (ICUs) collapse. Amalgams of sedative agents (including volatile anesthetics) were used due to the clinical shortage of intravenous drugs (mainly propofol and midazolam). METHODS: A multicenter, randomized 1:1, controlled clinical trial was designed to compare sedation using propofol and sevoflurane in patients with ARDS associated with COVID-19 infection in terms of oxygenation and mortality. RESULTS: Data from a total of 17 patients (10 in the propofol arm and 7 in the sevoflurane arm) showed a trend toward PaO2/FiO2 improvement and the sevoflurane arm's superiority in decreasing the likelihood of death (no statistical significance was found). CONCLUSIONS: Intravenous agents are the most-used sedative agents in Spain, even though volatile anesthetics, such as sevoflurane and isoflurane, have shown beneficial effects in many clinical conditions. Growing evidence demonstrates the safety and potential benefits of using volatile anesthetics in critical situations.

DNA Damage Protection for Enhanced Bacterial Survival Under Simulated Low Earth Orbit Environmental Conditions in Escherichia coli.

Some organisms have shown the ability to naturally survive in extreme environments, even outer space. Some of these have natural mechanisms to resist severe DNA damage from conditions such as ionizing and non-ionizing radiation, extreme temperatures, and low pressures or vacuum. A good example can be found in Deinococcus radiodurans, which was exposed to severe conditions such as those listed in the Exposure Facility of the International Space Station (ISS) for up to three years. Another example are tardigrades (Ramazzottius varieornatus) which are some of the most resilient animals known. In this study, the survival under simulated Low earth Orbit (LEO) environmental conditions was tested in Escherichia coli. The radiation resistance of this bacteria was enhanced using the Dsup gene from R. varieornatus, and two more genes from D. radiodurans involved in DNA damage repair, RecA and uvrD. The enhanced survival to wide ranges of temperatures and low pressures was then tested in the new strains. This research constitutes a first step in the creation of new bacterial strains engineered to survive severe conditions and adapting existing species for their survival in remote environments, including extra-terrestrial habitats. These strains could be key for the development of environments hospitable to life and could be of use for ecological restoration and space exploration. In addition, studying the efficacy and the functioning of the DNA repair mechanisms used in this study could be beneficial for medical and life sciences engineering.

High-flow nasal cannula oxygenation reduces postoperative hypoxemia in morbidly obese patients: a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPCs) are common in high-risk surgical patients. Postoperative ventilatory management may improve their outcome. Supplemental oxygen through a high-flow nasal cannula (HFNC) has become an alternative to classical oxygenation techniques, although the results published for postoperative patients are contradictory. We examined the efficacy of HFNC in postoperative morbidly obese patients who were ventilated intraoperatively with an open-lung approach (OLA). METHODS: We performed an open, two-arm, randomized controlled trial in 64 patients undergoing bariatric surgery (N.=32 in each arm) from May to November 2017 at the Hospital Clínico of Valencia. Patients were randomly assigned to receive HFNC oxygen therapy at the time of extubation or to receive conventional oxygen therapy, both applied during the first three postoperative hours. Intraoperatively, a recruitment maneuver and individualized positive end-expiratory pressure was applied in all patients. The primary outcome was postoperative hypoxemia. RESULTS: All patients were included in the final analysis. There were no significant differences between the baseline characteristics. Postoperative hypoxemia was less frequent in the HFNC group compared to those who received standard care (28.6% vs. 80.0%, relative risk [RR]: 0.35; 95%CI: 0.150-0.849, P=0.009). Prevalence of atelectasis was lower in the HFNC group (31% vs. 77%, RR: 0.39; 95%CI: 0.166-0.925, P=0.013). No severe PPCs were reported in any patient. CONCLUSIONS: Early application of HFNC in the operating room before extubation and during the immediate postoperative period decreases postoperative hypoxemia in obese patients after bariatric surgery who were intraoperatively ventilated using an OLA approach.

Individualized, perioperative, hemodynamic goal-directed therapy in major abdominal surgery (iPEGASUS trial): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative morbidity and mortality in patients undergoing surgery is high, especially in patients who are at risk of complications and undergoing major surgery. We hypothesize that perioperative, algorithm-driven, hemodynamic therapy based on individualized fluid status and cardiac output optimization is able to reduce mortality and postoperative moderate and severe complications as a major determinant of the patients' postoperative quality of life, as well as health care costs. METHODS/DESIGN: This is a multi-center, international, prospective, randomized trial in 380 patients undergoing major abdominal surgery including visceral, urological, and gynecological operations. Eligible patients will be randomly allocated to two treatment arms within the participating centers. Patients of the intervention group will be treated perioperatively following a specific hemodynamic therapy algorithm based on pulse-pressure variation (PPV) and individualized optimization of cardiac output assessed by pulse-contour analysis (ProAQT© device; Pulsion Medical Systems, Feldkirchen, Germany). Patients in the control group will be treated according to standard local care based on established basic hemodynamic treatment. The primary endpoint is a composite comprising the occurrence of moderate or severe postoperative complications or death within 28 days post surgery. Secondary endpoints are: (1) the number of moderate and severe postoperative complications in total, per patient and for each individual complication; (2) the occurrence of at least one of these complications on days 1, 3, 5, 7, and 28 in total and for every complication; (3) the days alive and free of mechanical ventilation, vasopressor therapy and renal replacement therapy, length of intensive care unit, and hospital stay at day 7 and day 28; and (4) mortality and quality of life, assessed by the EQ-5D-5L™ questionnaire, after 6 months. DISCUSSION: This is a large, international randomized controlled study evaluating the effect of perioperative, individualized, algorithm-driven ,hemodynamic optimization on postoperative morbidity and mortality. TRIAL REGISTRATION: Trial registration: NCT03021525 . Registered on 12 January 2017.

Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial.

BACKGROUND: The effects of individualised perioperative lung-protective ventilation (based on the open-lung approach [OLA]) on postoperative complications is unknown. We aimed to investigate the effects of intraoperative and postoperative ventilatory management in patients scheduled for abdominal surgery, compared with standard protective ventilation. METHODS: We did this prospective, multicentre, randomised controlled trial in 21 teaching hospitals in Spain. We enrolled patients who were aged 18 years or older, were scheduled to have abdominal surgery with an expected time of longer than 2 h, had intermediate-to-high-risk of developing postoperative pulmonary complications, and who had a body-mass index less than 35 kg/m2. Patients were randomly assigned (1:1:1:1) online to receive one of four lung-protective ventilation strategies using low tidal volume plus positive end-expiratory pressure (PEEP): open-lung approach (OLA)-iCPAP (individualised intraoperative ventilation [individualised PEEP after a lung recruitment manoeuvre] plus individualised postoperative continuous positive airway pressure [CPAP]), OLA-CPAP (intraoperative individualised ventilation plus postoperative CPAP), STD-CPAP (standard intraoperative ventilation plus postoperative CPAP), or STD-O2 (standard intraoperative ventilation plus standard postoperative oxygen therapy). Patients were masked to treatment allocation. Investigators were not masked in the operating and postoperative rooms; after 24 h, data were given to a second investigator who was masked to allocations. The primary outcome was a composite of pulmonary and systemic complications during the first 7 postoperative days. We did the primary analysis using the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02158923. FINDINGS: Between Jan 2, 2015, and May 18, 2016, we enrolled 1012 eligible patients. Data were available for 967 patients, whom we included in the final analysis. Risk of pulmonary and systemic complications did not differ for patients in OLA-iCPAP (110 [46%] of 241, relative risk 0·89 [95% CI 0·74-1·07; p=0·25]), OLA-CPAP (111 [47%] of 238, 0·91 [0·76-1·09; p=0·35]), or STD-CPAP groups (118 [48%] of 244, 0·95 [0·80-1·14; p=0·65]) when compared with patients in the STD-O2 group (125 [51%] of 244). Intraoperatively, PEEP was increased in 69 (14%) of patients in the standard perioperative ventilation groups because of hypoxaemia, and no patients from either of the OLA groups required rescue manoeuvres. INTERPRETATION: In patients who have major abdominal surgery, the different perioperative open lung approaches tested in this study did not reduce the risk of postoperative complications when compared with standard lung-protective mechanical ventilation. FUNDING: Instituto de Salud Carlos III of the Spanish Ministry of Economy and Competitiveness, and Grants Programme of the European Society of Anaesthesiology.

Performance of the New Turbine Mid-Level Critical Care Ventilators.

BACKGROUND: During recent years, ventilators using turbines as flow-generating systems have become increasingly more relevant. This bench study was designed to compare triggering and pressurization of 7 turbine mid-level ICU ventilators. METHODS: We used a dual-chamber lung model to test 7 mid-level ICU ventilators in pressure support mode with levels of 10, 15, and 20 cm H2O with 2 PEEP levels of 5 cm H2O and the minimum level allowed by the ventilator. A ventilator was connected to the master chamber to simulate 2 different effort levels. Pressure drop, trigger delay time, time to minimum pressure, and pressure time products (PTP) during trigger and the first 300 and 500 ms were analyzed. RESULTS: In the trigger evaluation, the Savina had the highest delay time, whereas the C2, the V60, and the Trilogy had the lowest pressure drops and PTP values in both effort levels. In pressurization capacity assessment using ideal PTP300 and PTP500 percentages, the C2 and the V680 had the best results, and the Carina and the Savina had lower values, with no differences between both effort levels. Differences between PEEP levels did not seem to be relevant. CONCLUSIONS: Pressure support mode for tested ventilators worked properly, but pressurization capacity and trigger function performance were clearly superior in the newest machines. The use of PEEP did not modify the results.

Current dilemmas in the diagnosis and management of follicular thyroid tumors.

Follicular carcinoma (FTC) is a relatively uncommon type of differentiated thyroid carcinoma. Guidelines have often dealt with FTC and papillary thyroid cancer as a single disease. Over the last decade, however, a better understanding of these two types of thyroid cancer indicates that they cannot be analysed together. Neither ultrasonography nor fine-needle aspiration cytology can provide a clear distinction between FTC and follicular adenoma. New molecular diagnostic techniques may be used to identify a subpopulation of follicular neoplasms with a low probability of being malignant. Diagnostic surgery-usually hemithyroidectomy- is recommended for most thyroid follicular lesions without a certain preoperative diagnosis. If FTC is diagnosed most-perhaps not all- patients will require a completion thyroidectomy. While widely invasive FTC usually does not pose diagnostic or therapeutic doubts, consensus on the diagnosis of non-invasive follicular lesions is still lacking. Prognosis of FTC is mostly dependent on local invasion and distant metastasis that, in turn, correlate with tumor size.

Anidulafungin dosing in critically ill patients with continuous venovenous haemodiafiltration.

BACKGROUND: Anidulafungin is indicated as a first-line treatment for invasive candidiasis in critically ill patients. In the intensive care unit, sepsis is the main cause of acute renal failure, and treatment with continuous renal replacement therapy (CRRT) has increased in recent years. Antimicrobial pharmacokinetics is affected by CRRT, but few studies have addressed the optimal dosage for anidulafungin during CRRT. PATIENTS AND METHODS: We included 12 critically ill patients who received continuous venovenous haemodiafiltration to treat acute renal failure. Anidulafungin was infused on 3 consecutive days, starting with a loading dose (200 mg) on Day 1, and doses of 100 mg on Days 2 and 3. Blood and ultradiafiltrate samples were collected on Day 3 (during steady-state) before, and at regular intervals after, the infusion had started. Anidulafungin concentrations were determined with HPLC. RESULTS: On Day 3, peak plasma concentrations with the 100 mg dose were 6.2 ±â€Š1.7 mg/L and 7.1 ±â€Š1.9 mg/L in the arterial and venous samples, respectively. The mean, pre-filter trough concentration was 3.0 ±â€Š0.6 mg/L. The mean AUC0-24 values for plasma anidulafungin were 93.9 ±â€Š19.4 and 104.1 ±â€Š20.3mg·h/L in the arterial and venous samples, respectively. There was no adsorption to synthetic surfaces, and the anidulafungin concentration in the ultradiafiltrate was below the limit of detection. CONCLUSION: The influence of CRRT on anidulafungin elimination appeared to be negligible. Therefore, we recommend no adjustments to the anidulafungin dose for patients receiving CRRT.

Perioperative goal-directed hemodynamic therapy based on radial arterial pulse pressure variation and continuous cardiac index trending reduces postoperative complications after major abdominal surgery: a multi-center, prospective, randomized study.

INTRODUCTION: Several single-center studies and meta-analyses have shown that perioperative goal-directed therapy may significantly improve outcomes in general surgical patients. We hypothesized that using a treatment algorithm based on pulse pressure variation, cardiac index trending by radial artery pulse contour analysis, and mean arterial pressure in a study group (SG), would result in reduced complications, reduced length of hospital stay and quicker return of bowel movement postoperatively in abdominal surgical patients, when compared to a control group (CG). METHODS: 160 patients undergoing elective major abdominal surgery were randomized to the SG (79 patients) or to the CG (81 patients). In the SG hemodynamic therapy was guided by pulse pressure variation, cardiac index trending and mean arterial pressure. In the CG hemodynamic therapy was performed at the discretion of the treating anesthesiologist. Outcome data were recorded up to 28 days postoperatively. RESULTS: The total number of complications was significantly lower in the SG (72 vs. 52 complications, p = 0.038). In particular, infection complications were significantly reduced (SG: 13 vs. CG: 26 complications, p = 0.023). There were no significant differences between the two groups for return of bowel movement (SG: 3 vs. CG: 2 days postoperatively, p = 0.316), duration of post anesthesia care unit stay (SG: 180 vs. CG: 180 minutes, p = 0.516) or length of hospital stay (SG: 11 vs. CG: 10 days, p = 0.929). CONCLUSIONS: This multi-center study demonstrates that hemodynamic goal-directed therapy using pulse pressure variation, cardiac index trending and mean arterial pressure as the key parameters leads to a decrease in postoperative complications in patients undergoing major abdominal surgery. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01401283.

Biochemical behaviour of an incidentally diagnosed silent corticotroph adenoma.

Silent corticotroph adenoma (SCA) is a non-functioning macroadenoma that has positive immunoreactivity for ACTH. Few studies have evaluated the biochemical behaviour of these tumours. We present the case of a 65-year-old male incidentally diagnosed with SCA, in which an exhaustive study of the corticotroph axis was conducted.

Síndrome metabólico y diabetes mellitus tipo 1: prevalencia y factores relacionados / Metabolic syndrome and type-1 diabetes mellitus: prevalence and associated factors

Introducción y objetivos. Numerosas evidencias han puesto de relieve la importancia clínica y epidemiológica del síndrome metabólico como precursor de la enfermedad cardiovascular. El síndrome metabólico se asocia en general a la diabetes tipo 2, pero son escasos los datos en la diabetes tipo 1. En el presente estudio se evalúa la prevalencia de síndrome metabólico en pacientes con diabetes tipo 1 y los factores relacionados. Métodos. Estudio transversal que incluyó a los pacientes mayores de 18 años de edad con diabetes tipo 1 autoinmune de más de 6 meses de evolución atendidos consecutivamente en la Consulta Externa de Endocrinología del Hospital del Mar de Barcelona durante el año 2008. La identificación del síndrome metabólico se estableció según los criterios modificados del Panel III del National Cholesterol Education Program. Resultados. Tenía síndrome metabólico el 31,9% (intervalo de confianza [IC] del 95%, 22,3%-41,5%) de los pacientes con diabetes tipo 1. La edad (odds ratio [OR] = 1,09; IC del 95%, 1,029-1,154), el índice de masa corporal (OR = 1,389; IC del 95%, 1,134-1,702) y la glucohemoglobina (OR = 1,745; IC del 95%, 1,081-2,815) fueron los factores que se asociaron de forma independiente y significativa con la presencia de síndrome metabólico en los pacientes con diabetes tipo 1. Se constató una relación directa entre el número de componentes de síndrome metabólico y la prevalencia de microangiopatía, que llegó a ser del 100% en los pacientes que cumplían todos los criterios diagnósticos. Conclusiones. El síndrome metabólico es frecuente en los pacientes con diabetes tipo 1 y se asocia con las complicaciones microvasculares (AU)

Introduction and objectives. Numerous clinical and epidemiological studies have highlighted the fact that metabolic syndrome is an important precursor of cardiovascular disease. Metabolic syndrome is generally associated with type-2 diabetes, and few data exist on its occurrence in type-1 diabetes. The aims of this study were to determine the prevalence of metabolic syndrome in patients with type-1 diabetes and to identify associated factors. Methods. This cross-sectional study included consecutive patients aged over 18 years with autoimmune type-1 diabetes of more than 6 months’ duration who were treated during 2008 at the Outpatient Endocrinology Clinic of the Hospital del Mar, Barcelona, Spain. The presence of metabolic syndrome was determined using the modified criteria proposed by the National Cholesterol Education Program-Adult Treatment Panel III. Results. Overall, 31.9% (95% confidence interval [CI], 22.3%-41.5%) of patients with type-1 diabetes had metabolic syndrome. The following factors were significantly and independently associated with the presence of metabolic syndrome in patients with type-1 diabetes: age (odds ratio [OR]=1.09; 95% CI, 1.029-1.154), body mass index (OR=1.389; 95% CI, 1.134-1.702) and glycosylated hemoglobin level (OR=1.745; 95% CI, 1.081-2.815). In addition, there was a direct relationship between the number of components of metabolic syndrome present and prevalence of microangiopathy, which reached 100% in patients who satisfied all diagnostic criteria. Conclusions. Metabolic syndrome was common in patients with type-1 diabetes and was associated with microvascular complications (AU)

[Metabolic syndrome and type-1 diabetes mellitus: prevalence and associated factors]. / Síndrome metabólico y diabetes mellitus tipo 1: prevalencia y factores relacionados.

INTRODUCTION AND OBJECTIVES: Numerous clinical and epidemiological studies have highlighted the fact that metabolic syndrome is an important precursor of cardiovascular disease. Metabolic syndrome is generally associated with type-2 diabetes, and few data exist on its occurrence in type-1 diabetes. The aims of this study were to determine the prevalence of metabolic syndrome in patients with type-1 diabetes and to identify associated factors. METHODS: This cross-sectional study included consecutive patients aged over 18 years with autoimmune type-1 diabetes of more than 6 months' duration who were treated during 2008 at the Outpatient Endocrinology Clinic of the Hospital del Mar, Barcelona, Spain. The presence of metabolic syndrome was determined using the modified criteria proposed by the National Cholesterol Education Program-Adult Treatment Panel III. RESULTS: Overall, 31.9% (95% confidence interval [CI], 22.3%-41.5%) of patients with type-1 diabetes had metabolic syndrome. The following factors were significantly and independently associated with the presence of metabolic syndrome in patients with type-1 diabetes: age (odds ratio [OR]=1.09; 95% CI, 1.029-1.154), body mass index (OR=1.389; 95% CI, 1.134-1.702) and glycosylated hemoglobin level (OR=1.745; 95% CI, 1.081-2.815). In addition, there was a direct relationship between the number of components of metabolic syndrome present and prevalence of microangiopathy, which reached 100% in patients who satisfied all diagnostic criteria. CONCLUSIONS: Metabolic syndrome was common in patients with type-1 diabetes and was associated with microvascular complications.

Estimated glucose disposal rate in assessment of the metabolic syndrome and microvascular complications in patients with type 1 diabetes.

OBJECTIVE: The objective of the study was to quantify insulin resistance in type 1 diabetes patients by estimated glucose disposal rate (eGDR), according to the presence or absence of the metabolic syndrome, and its relationship with chronic complications. DESIGN: This was a cross-sectional study in 91 patients with type 1 immune-mediated diabetes managed at an outpatient endocrinology clinic. All participants were Caucasians aged 18 yr or older with type 1 diabetes duration of more than 6 months who had completed the study protocol. RESULTS: Twenty-nine patients met metabolic syndrome criteria, yielding a prevalence of 31.9%. Although no differences in insulin requirements were found between diabetic patients with and without metabolic syndrome, lower eGDR levels, indicating greater insulin resistance, were observed in metabolic syndrome patients compared with those without (6.19 +/- 1.5 mg/kg(-1) x min(-1) vs. 9.93 +/- 1.6 mg/kg(-1) x min(-1)) (P < 0.001). An eGDR level less than 8.77 mg/kg(-1) x min(-1) showed 100% sensitivity and 85.2% specificity for metabolic syndrome diagnosis. All patients with diabetes complications had eGDR values below 8.16 mg/kg(-1) x min(-1). eGDR level was significantly lower in patients with diabetic retinopathy (5.97 +/- 1.2 mg/kg(-1) x min(-1)), diabetic neuropathy (5.06 +/- 0.4 mg/kg(-1) x min(-1)), or diabetic nephropathy (5.79 +/- 1.5 mg/kg(-1) x min(-1)) compared with those without (9.38 +/- 2.0 mg/kg(-1) x min(-1), P < 0.001; 9.26 +/- 2.0 mg/kg(-1) x min(-1), P < 0.001; and 9.19 +/- 2.2 mg/kg(-1) x min(-1), P < 0.001). CONCLUSIONS: Insulin resistance is common in type 1 diabetes patients and is associated with microvascular complications. eGDR, as an insulin resistance marker, provides more useful information than other classical variables such as insulin requirements.

Intraoperative gamma probe detection of lymph node recurrence of insulinoma.

Insulinomas are rare endocrine tumors that are mostly sporadic, benign, and small. Preoperative radiography diagnosis may be difficult. Intraoperative palpation and ultrasound remain the gold standard for detection and planned resection. Recent studies find intraoperative gamma-probe localization as a good technique for identifying primary neuroendocrine tumors. We report a case of a 75-year-old woman with functioning lymph node recurrence of a malignant insulinoma. Spleno-pancreatectomy was performed in order to treat the malignant insulinoma. Clinical, biochemical, and radiological examination confirmed the total excision of the primary lesion. However, clinical symptoms appeared 9 months later. Octreo-scan, abdominal CT, and biochemical study showed lymph node recurrence and four hepatic metastases. Surgery was performed after two [111In-DTPA] octreotide scans. Intraoperative gamma probe detection was planned in order to localize a small latero-aortic lymph node recurrence. Intraoperative count rates were high in para-aortic tissue. Para-aortic lymphadenectomy and metastasectomy were carried out. Ex-situ count rates and histological examination confirmed the recurrence. Six months later clinical and biochemical studies and scans remain negative for recurrence. Intraoperative [111In-DTPA] octreotide gamma probe examination may be a useful tool in the surgical approach to insulinoma recurrence.

Unidad de estancia corta: una forma de optimizar recursos hospitalarios / No disponible

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