Collective effects of rising average temperatures and heat events on oviparous embryos.

Survival of the immobile embryo in response to rising temperature is important to determine a species' vulnerability to climate change. However, the collective effects of 2 key thermal characteristics associated with climate change (i.e., rising average temperature and acute heat events) on embryonic survival remain largely unexplored. We used empirical measurements and niche modeling to investigate how chronic and acute heat stress independently and collectively influence the embryonic survival of lizards across latitudes. We collected and bred lizards from 5 latitudes and incubated their eggs across a range of temperatures to quantify population-specific responses to chronic and acute heat stress. Using an embryonic development model parameterized with measured embryonic heat tolerances, we further identified a collective impact of embryonic chronic and acute heat tolerances on embryonic survival. We also incorporated embryonic chronic and acute heat tolerance in hybrid species distribution models to determine species' range shifts under climate change. Embryos' tolerance of chronic heat (T-chronic) remained consistent across latitudes, whereas their tolerance of acute heat (T-acute) was higher at high latitudes than at low latitudes. Tolerance of acute heat exerted a more pronounced influence than tolerance of chronic heat. In species distribution models, climate change led to the most significant habitat loss for each population and species in its low-latitude distribution. Consequently, habitat for populations across all latitudes will shift toward high latitudes. Our study also highlights the importance of considering embryonic survival under chronic and acute heat stresses to predict species' vulnerability to climate change.

Efectos colectivos del aumento de las temperaturas promedio y los eventos de calor en embriones ovíparos Resumen La supervivencia de los embriones inmóviles en respuesta al incremento de temperatura es importante para determinar la vulnerabilidad de las especies al cambio climático. Sin embargo, los efectos colectivos de dos características térmicas claves asociadas con el cambio climático (i. e., aumento de temperatura promedio y eventos de calor agudo) sobre la supervivencia embrionaria permanecen en gran parte inexplorados. Utilizamos mediciones empíricas y modelos de nicho para investigar cómo el estrés térmico crónico y agudo influye de forma independiente y colectiva en la supervivencia embrionaria de los lagartos en todas las latitudes. Recolectamos y criamos lagartos de cinco latitudes e incubamos sus huevos en un rango de temperaturas para cuantificar las respuestas específicas de la población al estrés por calor crónico y agudo. Posteriormente, mediante un modelo de desarrollo embrionario parametrizado con mediciones de tolerancia embrionaria al calor, identificamos un impacto colectivo de las tolerancias embrionarias al calor agudo y crónico en la supervivencia embrionaria. También incorporamos la tolerancia embrionaria crónica y aguda al calor en modelos de distribución de especies híbridas para determinar los cambios de distribución de las especies bajo el cambio climático. La tolerancia embrionaria al calor crónico (T­crónico) permaneció constante, mientras que la tolerancia al calor agudo (T­agudo) fue mayor en latitudes altas que en latitudes bajas. La tolerancia al calor agudo ejerció una influencia más pronunciada que la tolerancia al calor crónico. En los modelos de distribución de especies, el cambio climático provocó la pérdida de hábitat más significativa para cada población y especie en su distribución de latitudes bajas. En consecuencia, el hábitat para poblaciones en todas las latitudes se desplazará a latitudes altas. Nuestro estudio también resalta la importancia de considerar la supervivencia embrionaria bajo estrés térmico crónico y agudo para predecir la vulnerabilidad de las especies al cambio climático.

Feasibility of low-dose dexmedetomidine for prevention of postoperative delirium after intracranial operations: a pilot randomized controlled trial.

BACKGROUND: Clinical trials have shown that dexmedetomidine might decrease the occurrence of postoperative delirium after major surgery, but neurosurgical patients were excluded from these studies. We aimed to determine the feasibility of conducting a full-scale randomized controlled trial of the effect of prophylactic low-dose dexmedetomidine on postoperative delirium in patients after elective intracranial operation for brain tumors. METHODS: In this single-center, parallel-arm pilot randomized controlled trial, adult patients who underwent an elective intracranial operation for brain tumors were recruited. Dexmedetomidine (0.1 µg/kg/hour) or placebo was continuously infused from intensive care unit (ICU) admission on the day of surgery until 08:00 AM on postoperative day one. Adverse events during the study-drug administration were recorded. The primary feasibility endpoint was the occurrence of study-drug interruption. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU during the first five postoperative days. The assessable rate of delirium evaluation was documented. RESULTS: Sixty participants were randomly assigned to receive either dexmedetomidine (n = 30) or placebo (n = 30). The study-drug was stopped in two patients (6.7%) in the placebo group due to desaturation after new-onset unconsciousness and an unplanned reoperation for hematoma evacuation and in one patient (3.3%) in the dexmedetomidine group due to unplanned discharge from the ICU. The absolute difference (95% confidence interval) of study-drug interruption between the two groups was 3.3% (- 18.6 to 12.0%), with a noninferiority P value of 0.009. During the study-drug infusion, no bradycardia occurred, and hypotension occurred in one patient (3.3%) in the dexmedetomidine group. Dexmedetomidine tended to decrease the incidence of tachycardia (10.0% vs. 23.3%) and hypertension (3.3% vs. 23.3%). Respiratory depression, desaturation, and unconsciousness occurred in the same patient with study-drug interruption in the placebo group (3.3%). Delirium was evaluated 600 times, of which 590 (98.3%) attempts were assessable except in one patient in the placebo group who remained in a coma after an unplanned reoperation. CONCLUSIONS: The low rate of study-drug interruption and high assessable rate of delirium evaluation supported a fully powered trial to determine the effectiveness of low-dose dexmedetomidine on postoperative delirium in patients after intracranial operation for brain tumors. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT04494828) on 31/07/2020.

Dexmedetomidine for the prevention of postoperative delirium in patients after intracranial operation for brain tumours (DEPOD study): a study protocol and statistical plan for a multicentre randomised controlled trial.

INTRODUCTION: Postoperative delirium (POD) is prevalent in patients after major surgery and is associated with adverse outcomes. Several studies have reported that dexmedetomidine, a highly selective α2-adrenergic receptor agonist, can decrease the incidence of POD. However, neurosurgical patients are usually excluded from previous studies. The present study was designed to investigate the impact of prophylactic use of low-dose dexmedetomidine on the incidence of POD in patients after intracranial operation. METHODS AND ANALYSIS: This is a multicentre, randomised, double-blinded and placebo-controlled trial. Seven hundred intensive care unit admitted patients after elective intracranial operation for brain tumours under general anaesthesia are randomly assigned to the dexmedetomidine group or the placebo group with a 1:1 ratio. For patients in the dexmedetomidine group, a continuous infusion of dexmedetomidine will be started at a rate of 0.1 µg/kg/hour immediately after enrolment on the day of operation and continued until 08:00 on postoperative day 1. For patients in the placebo group, normal saline will be administered at the same rate as in the dexmedetomidine group. The patients will be followed up for 28 days after enrolment. The primary endpoint is the incidence of POD, which is assessed two times per day using the Confusion Assessment Method for the intensive care unit (ICU), during the first 5 postoperative days. The secondary endpoints include the incidence of dexmedetomidine-related adverse events and non-delirium complications, the length of stay in the ICU and hospital and all-cause 28-day mortality after the operation. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board of Beijing Tiantan Hospital Affiliated to Capital Medical University (No KY2019-091-02) and registered at ClinicalTrials.gov. The results of the trial will be presented at national and international conferences relevant to subject fields and submitted to international peer-reviewed journals. TRIAL REGISTRATION NUMBER: Trial registration number: NCT04399343; Pre-results.

Derecruitment volume assessment derived from pressure-impedance curves with electrical impedance tomography in experimental acute lung injury.

OBJECTIVE: To investigate the accuracy of derecruitment volume (VDER) assessed by pressure-impedance (P-I) curves derived from electrical impedance tomography (EIT). METHODS: Six pigs with acute lung injury received decremental positive end-expiratory pressure (PEEP) from 15 to 0 in steps of 5 cmH2O. At the end of each PEEP level, the pressure-volume (P-V) curves were plotted using the low constant flow method and release maneuvers to calculate the VDER between the PEEP of setting levels and 0 cmH2O (VDER-PV). The VDER derived from P-I curves that were recorded simultaneously using EIT was the difference in impedance at the same pressure multiplied by the ratio of tidal volume and corresponding tidal impedance (VDER-PI). The regional P-I curves obtained by EIT were used to estimate VDER in the dependent and nondependent lung. RESULTS: The global lung VDER-PV and VDER-PI showed close correlations (r = 0.948, P<0.001); the mean difference was 48 mL with limits of agreement of -133 to 229 mL. Lung derecruitment extended into the whole process of decremental PEEP levels but was unevenly distributed in different lung regions. CONCLUSIONS: P-I curves derived from EIT can assess VDER and provide a promising method to estimate regional lung derecruitment at the bedside.

Effect of positive end-expiratory pressure on functional residual capacity in two experimental models of acute respiratory distress syndrome.

OBJECTIVE: Measurement of positive end-expiratory pressure (PEEP)-induced recruitment lung volume using passive spirometry is based on the assumption that the functional residual capacity (FRC) is not modified by the PEEP changes. We aimed to investigate the influence of PEEP on FRC in different models of acute respiratory distress syndrome (ARDS). METHODS: A randomized crossover study was performed in 12 pigs. Pulmonary (n = 6) and extra-pulmonary (n = 6) ARDS models were established using an alveolar instillation of hydrochloric acid and a right atrium injection of oleic acid, respectively. Low (5 cmH2O) and high (15 cmH2O) PEEP were randomly applied in each animal. FRC and recruitment volume were determined using the nitrogen wash-in/wash-out technique and release maneuver. RESULTS: FRC was not significantly different between the two PEEP levels in either pulmonary ARDS (299 ± 92 mL and 309 ± 130 mL at 5 and 15 cmH2O, respectively) or extra-pulmonary ARDS (305 ± 143 mL and 328 ± 197 mL at 5 and 15 cmH2O, respectively). The recruitment volume was not significantly different between the two models (pulmonary, 341 ± 100 mL; extra-pulmonary, 351 ± 170 mL). CONCLUSIONS: PEEP did not influence FRC in either the pulmonary or extra-pulmonary ARDS pig model.

Use of Electrical Impedance Tomography (EIT) to Estimate Global and Regional Lung Recruitment Volume (VREC) Induced by Positive End-Expiratory Pressure (PEEP): An Experiment in Pigs with Lung Injury.

BACKGROUND Electrical impedance tomography (EIT) is a real-time tool used to monitor lung volume change at the bedside, which could be used to measure lung recruitment volume (VREC) for setting positive end-expiratory pressure (PEEP). We assessed and compared the agreement in VREC measurement with the EIT method versus the flow-derived method. MATERIAL AND METHODS In 12 Bama pigs, lung injury was induced by tracheal instillation of hydrochloric acid and verified by an arterial partial pressure of oxygen to inspired oxygen fraction ratio below 200 mmHg. During the end-expiratory occlusion, an airway release maneuver was conduct at 5 and 15 cmH2O of PEEP. VREC was measured by flow-integrated PEEP-induced lung volume change (flow-derived method) and end-expiratory lung impedance change (EIT-derived method). Linear regression and Bland-Altman analysis were used to test the correlation and agreement between these 2 measures. RESULTS Lung injury was successfully induced in all the animals. EIT-derived VREC was significantly correlated with flow-derived VREC (R²=0.650, p=0.002). The bias (the lower and upper limits of agreement) was -19 (-182 to 144) ml. The median (interquartile range) of EIT-derived VREC was 322 (218-469) ml, with 110 (59-142) ml and 194 (157-307) ml in dependent and nondependent lung regions, respectively. Global and regional respiratory system compliance increased significantly at high PEEP compared to those at low PEEP. CONCLUSIONS Close correlation and agreement were found between EIT-derived and flow-derived VREC measurements. The advantages of EIT-derived recruitability assessment included the avoidance of ventilation interruption and the ability to provide regional recruitment information.

Additional Expiratory Resistance Elevates Airway Pressure and Lung Volume during High-Flow Tracheal Oxygen via Tracheostomy.

The standard high-flow tracheal (HFT) interface was modified by adding a 5-cm H2O/L/s resistor to the expiratory port. First, in a test lung simulating spontaneous breathing, we found that the modified HFT caused an elevation in airway pressure as a power function of flow. Then, three tracheal oxygen treatments (T-piece oxygen at 10 L/min, HFT and modified HFT at 40 L/min) were delivered in a random crossover fashion to six tracheostomized pigs before and after the induction of lung injury. The modified HFT induced a significantly higher airway pressure compared with that in either T-piece or HFT (p < 0.001). Expiratory resistance significantly increased during modified HFT (p < 0.05) to a mean value of 4.9 to 6.7 cm H2O/L/s. The modified HFT induced significant augmentation in end-expiratory lung volume (p < 0.05) and improved oxygenation for lung injury model (p = 0.038) compared with the HFT and T-piece. There was no significant difference in esophageal pressure swings, transpulmonary driving pressure or pressure time product among the three treatments (p > 0.05). In conclusion, the modified HFT with additional expiratory resistance generated a clinically relevant elevation in airway pressure and lung volume. Although expiratory resistance increased, inspiratory effort, lung stress and work of breathing remained within an acceptable range.

Thermal dependence of feeding performance and resting metabolic expenditure in different altitudinal populations of toad-headed lizards.

Inter-population variations in growth rate can result from independent or interactive effects of genetic and environmental factors, and be induced by some physiological differences as well. Toad-headed lizards (Phrynocephalus vlangalii) from a higher-elevation population were shown to have a higher growth rate than those from a lower-elevation population. The physiological basis of growth rate variation in this species is not well understood. Here, we investigated the feeding performance and resting metabolic rate (RMR) of lower- and higher-elevation individuals at different test ambient temperatures to evaluate the role of differences in energy intake, assimilation efficiency and metabolic expenditure on growth rate variations. Within the range of 25-35 °C, lizard RMR increased with increasing test ambient temperature, but food intake, apparent digestive coefficient (ADC, food energy minus faecal energy divided by food energy), and assimilation efficiency (AE, food energy minus faecal and urinary energy divided by food energy) were less thermally sensitive in both populations. Higher-elevation lizards tended to eat more food and have a lower RMR than lower-elevation ones, despite the lack of differences in ADC and AE. Our result showed that more energy intake and reduced maintenance cost may be associated with the higher growth rate of higher-elevation lizards. Accordingly, inter-population differences in energy acquisition and expenditure could act as potential sources for geographic variation in growth rate.