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At least 19 records

Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia

Abstract Background Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability of outcome ranking (DOOR) is a paradigm for the design, analysis, and interpretation of clinical trials based on a patient-centered, benefit-risk evaluation. Methods A multidisciplinary committee created an infectious diseases DOOR endpoint customized for HABP/VABP, incorporating infectious complications, serious adverse events, and mortality. We applied this to 2 previously completed, large randomized controlled trials for HABP/VABP. ZEPHyR compared vancomycin to linezolid and VITAL compared linezolid to tedizolid. For each trial, we evaluated the DOOR distribution and probability, including DOOR component and partial credit analyses. We also applied DOOR in subgroup analyses. Results In both trials, the HABP/VABP DOOR demonstrated similar overall clinical outcomes between treatment groups. In ZEPHyR, the probability that a participant treated with linezolid would have a more desirable outcome than a participant treated with vancomycin was 50.2% (95% confidence interval [CI], 45.1%­−55.3%). In VITAL, the probability that a participant treated with tedizolid would have a more desirable outcome than a participant treated with linezolid was 48.7% (95% CI, 44.8%–52.6%). The DOOR component analysis revealed that participants treated with tedizolid had a less desirable outcome than those treated with linezolid when considering clinical response alone. However, participants with decreased renal function had improved overall outcomes with tedizolid. Conclusions The HABP/VABP DOOR provided more granular information about clinical outcomes than is typically presented in clinical trials. HABP/VABP trials would benefit from prospectively using DOOR.

Immunology↗

Smart Ventilation Controls for Occupancy and Auxiliary Fan Use Across U.S. Climates

Smart Ventilation has been developed as a way to reduce the energy associated with ventilation by changing when ventilation happens and how much ventilation occurs at any given time. In high performance buildings with low envelope and appliance related loads, ventilation is becoming a bigger part of the total building energy use and needs to be addressed if performance targets are to be met. This work explores the development and performance of smart ventilation controls based on occupancy and auxiliary fan operation that provide annual dwelling unit ventilation equivalence to ASHRAE Standard 62.2-2016. A prototype high performance home compliant with U.S. DOE Building America Zero Energy Ready program requirements was simulated using the REGCAP tool with and without smart controls across 15 U.S. DOE climate zones. Balanced and unbalanced IAQ fans were independently simulated, and all smart controlled fans had airflows double the reference 62.2-2016 airflow. Three idealized occupancy patterns were examined: 1st shift (a typical daily work/school absence), an extended 1st shift with more time spent out of the home evenings and weekends and 3rd shift (night work). The Occupancy controller turns the IAQ fan off during unoccupied periods, and it resumes ventilation upon their return. While unoccupied, contaminants are allowed to accumulate in the space, because occupants are not exposed to these contaminants. When occupants return home, they are exposed to these higher contaminant concentrations, and the controller increases the ventilation rate sufficiently to ensure equivalence with a continuous IAQ fan. Accounting for pollutant emissions that occur during unoccupied periods (as required by ASHRAE 62.2-2016), sharply distinguishes our occupancy controls from past Demand Controlled Ventilation systems. This new accounting method results in equivalent contaminant exposure, as well as lower reductions in average ventilation rates and lower energy savings. Smart controls were demonstrated that saved HVAC energy (i.e., avoided heating/cooling load, as well as fan energy)—averaging between 6 and 46% of ventilation-related energy use depending on the control strategy and occupancy pattern assumptions. The greatest savings were in the combined Auxiliary Fan + Occupancy control. Energy savings increased with climate heating demand and longer unoccupied time periods. The 3rd shift occupancy pattern had better performance, due to the thermal benefit of reducing the ventilation rate during the cold nighttime hours. This same effect provided a cooling energy benefit in hotter locations for the 1st shift. Overall, savings from occupancy-based smart controls were low, because of the recovery period required after occupants return home, during which the airflow is double the 62.2 reference. This recovery is required to maintain equivalence with the ASHRAE standard. Occupancy-based control performance was improved when combined with sensing auxiliary fans and when providing a pre-occupancy flush out of one- or two-hours. Performance was similarly improved if the ASHRAE Standard were to recognize that pollutant emissions are lower during unoccupied periods, iii allowing a lower target ventilation rate during unoccupied periods (not currently in the standard) (see Full vs. Half AEQ in this report). Finally, over-sized unbalanced fans that are cycled on-and-off by a smart controller (or timer) were found to substantially increase annual average air exchange and energy use relative to a continuous unbalanced fan due to the effects of superposition with natural infiltration.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Design And Control of Thermal Storage for Ventilative Cooling in Multifamily Buildings (Final Report)

The concept of natural ventilation is to provide a heat sink for cooling the building during the occupancy periods at night and improve indoor thermal comfort during the daytime without or with minimal need for mechanical cooling. Commonly, natural ventilation through the window or mechanical circulation of the air through the ventilation ducts are two key methods used to achieve night ventilation. Due to the increasing electric need for space heating and cooling, renewable energies combined with energy storage systems are receiving attention worldwide nowadays. When designed and controlled properly, this strategy can reduce energy use for cooling, reduce the size of mechanical cooling equipment, reduce peak electrical demand for cooling, and better enable demand flexibility for mechanical cooling equipment. In some cases, ventilative cooling can eliminate the need for mechanical cooling altogether. For these reasons, California’s Building Energy Efficiency Standards have recently added prescriptive requirements that all new single-family residences (in most California climates) must include ventilative cooling systems (aka: “whole house fans”). However, the current standards do not address multifamily buildings because market-available ventilative cooling products are designed for single-family residences and are physically incompatible with many multifamily building archetypes. The results from the study show that the combination of thermal energy storage on building walls along with nighttime ventilation cooling assisted with nighttime ventilation can save total building energy usage by up to 9% and peak load by 16% in moderate climate zones. The controlled nighttime ventilation cooling (activate ventilation only when outdoor conditions are favorable) can also provide total electricity savings of up to 5% and 7% in hot and cold climates, respectively. In the case of moderate climates, kitchen exhaust-assisted nighttime ventilation cooling can eliminate the need for cooling during overnight hours. This can also significantly assist in reducing carbon emissions.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Cooking methods and kitchen ventilation availability, usage, perceived performance and potential in Canadian homes

Cooking is a substantial contributor to air pollutant exposures in many residences. Effective use of kitchen ventilation can mitigate exposure; however, information on its availability, usage, and potential to increase its use across the population has been limited. This study aimed to obtain nationally representative information on cooking methods, kitchen ventilation availability and usage, and the potential for education to increase effective usage. An online survey was sent to a representative sample of Canadian homes to collect data on cooking methods, the presence and use of mechanical kitchen ventilation devices, perceived device performance, and willingness to implement mitigation strategies. Responses were weighted to match key demographic factors and analyzed using non-parametric statistics. Among the 4500 respondents, 90% had mechanical ventilation devices over the cooktop (66% of which were vented to the outside), and 30% reported regularly using their devices. Devices were used most often for deep-frying, followed by stir-frying, sautéing or pan-frying, indoor grilling, boiling or steaming. Almost half reported rarely or never using their ventilation devices during baking or oven self-cleaning. Only 10% were fully satisfied with their devices. More frequent use was associated with the device being vented to the outdoors, having more than two speed settings, quiet operation if only one speed, covering over half of the cooktop, and higher perceived effectiveness. After being informed of the benefits of kitchen ventilation, 64% indicated they would consider using their devices more often, preferentially using back burners with ventilation, and/or using higher ventilation device settings when needed. This study provides population-representative data on the most used cooking methods, kitchen ventilation availability and usage, and influencing factors in Canadian homes. Such data are needed for exposure assessments and evaluating the potential to mitigate cooking-related pollutant exposures via more effective use of kitchen ventilation. The data can be reasonably extrapolated to the United States, given the similarities in residential construction practices and cultural norms between the two countries.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Pilot Study for Multifamily Building Ventilation and Indoor Air Quality

Weatherization Program Notice (WPN) 17-7 issued by the US Department of Energy (DOE) Weatherization Assistance Program (WAP) requires that buildings have ventilation in accordance with ASHRAE Standard 62.2-2016 (entitled Ventilation and Indoor Air Quality in Residential Buildings) in dwelling units weatherized under the program. The 2016 version of the standard expanded its scope of application to include all multifamily dwelling units. This has resulted in concerns for buildings where installing ventilation in individual units is costly or otherwise logistically difficult. Also, excessive ventilation rates could significantly increase energy costs, and may cause indoor air quality issues within the buildings. One deficiency that is noted is that the standard does not provide a credit for existing infiltration in multifamily buildings that reduces the required mechanical ventilation levels. This report details findings from a field study investigating envelope air-tightness, inter-unit connectivity, and indoor air quality in centrally ventilated high-rise multifamily buildings with central ventilation systems serving individual units in the state of New York. As allowed under WPN 17-7, the State of New York has a variance in the application of ASHRAE Standard 62.2-2016 in select types of multifamily buildings to provide time to determine how best to implement the standard. The purpose of this pilot study is to characterize the impact that weatherization and feasible ventilation improvements have on the indoor air quality of large, multifamily buildings with centrally ventilated apartments, as currently performed under WAP in the State of New York under their variance request (i.e., to implement ASHRAE Standard 62.2-2016 “to the greatest extent possible” in this type of multifamily building). A major goal is to determine if these practices improve or at least “do no harm” to the indoor air quality of the weatherized multifamily buildings and to the occupants themselves.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

A review of experimental methods to determine bioaerosol transfer in energy recovery ventilators

Increasing ventilation is an effective method to reduce indoor airborne disease transmission. An Energy recovery ventilator (ERV) is a passive energy recovery device used to reduce the energy consumption of heating, ventilation and air-conditioning (HVAC) systems for conditioning the ventilation air. It preconditions the ventilation air by transferring energy from building exhaust air. Therefore, the ventilation and exhaust air streams interact directly/indirectly in the ERV for energy transfer. It is surmised that the ERV may transfer bioaerosols (with pathogens) from the exhaust air to ventilation air, resulting in the spread of infectious diseases. Consequently, many pandemic HVAC guidelines recommend that the use of ERVs be limited. This is a highly unsustainable direction given the increased energy requirements associated with the high ventilation provision advocated for pandemic operation. It must be noted that no validated experimental evidence exists in literature for bioaerosol transfer in ERVs. Hence, it is necessary to conduct extensive bioaerosol transfer research before adopting the unsustainable practice of limiting the utilization of ERVs. The main objective of this review study is to summarize the experimental methods and instrumentation for bioaerosol transfer research in ERVs. This comprehensive article provides a detailed overview of the generation, sampling, and analysis of bioaerosols for conducting the experiments. Further, it explains the possible mechanisms for bioaerosol transfer in various types of ERVs based on which the ERVs that need immediate attention are identified. The main contribution of this research paper is that it provides a novel experimental method which encompasses the biosafety aspects, instrumentation, performance parameters and uncertainties in conducting virus contained bioaerosol transfer study in ERVs. The findings from this review will be helpful in designing bioaerosol transfer experiments and developing future ERV test standards for such experiments.

42 ENGINEERING↗

Work Smarter, Not Harder: Improving Energy Efficiency and Safety through Smarter Ventilation: Preprint

Ventilation is a key component to maintaining healthy, safe indoor air quality. Especially important in laboratories, ventilation is the first line of defense against airborne hazards produced during research activities. Though a vital component, laboratory ventilation systems are often victim to ineffective operation, posing a risk to the most important asset - the researchers. Furthermore, system inefficiencies can lead to up to 50% wasted energy. To improve both energy efficiency and safety in laboratories, we present the Smart Labs Toolkit - a resource developed by the U.S. Department of Energy Federal Energy Management Program and the International Institute for Sustainable Laboratories that guides laboratory stakeholders through a straight-forward, holistic approach to achieve dynamic, high-performance laboratories. Smart Labs enable safe and efficient world class science to occur in laboratories through high-performance methods. A Smart Labs program employs a combination of physical, administrative, and management techniques to assess, optimize, and manage high performance laboratories. We will focus on a central component of the Smart Labs approach - the Laboratory Ventilation Risk Assessment, a systematic process for identifying risk due to airborne hazards to inform the operation of dynamic ventilation that optimizes safety and efficiency. Case studies of organizations who have successfully implemented Smart Labs ventilation management programs will also be shared. In learning ventilation strategies successful in critical laboratory environments, learn the tools and resources needed to successfully manage energy in any building through smarter, safer ventilation.

buildings↗

Existence of a Nonzero Worst‐Case ACH for Short‐Term Exposure in Ventilated Indoor Spaces

A well‐ventilated room is essential to reduce the risk of airborne transmission. As such, the scientific community sets minimum limits on ventilation with the idea that increased ventilation reduces pathogen concentration and thus reduces the risk of transmission. In contrast, the upper limit on ventilation is usually determined by human comfort and the need to reduce energy consumption. While average pathogen concentration decreases with increased ventilation, local concentration depends on multiple factors and may not follow the same trend, especially within short exposure times over large separation distances. Here, we show through experiments and high‐fidelity simulations the existence of a worst‐case ventilation where local pathogen concentration increases near the receiving host. This occurs during the type of meetings that were recommended during the pandemic (and in some cases solely authorized) with reduced occupancy adhering to social distancing and short exposure times below 20 minutes. We maintain that for cases of high occupancy and long exposure time, increased ventilation remains necessary.

Construction & Building Technology↗

Hardware-in-Loop Modules for Testing Automated Ventilator Controllers

Automated ventilator controllers have the potential to simplify oxygen and carbon dioxide management for trauma. In the pre-hospital or military medicine environment, trauma care can be required for prolonged periods by personnel with limited ventilator management training. As such, there is a need for closed-loop control systems that can adapt ventilator management to a complex, ever-changing medical environment. Here, we present a novel hardware-in-loop test platform for the independent troubleshooting and evaluation of oxygen and carbon dioxide automated ventilator management capabilities. The oxygen management system provides an analogue blood oxygen signal that is responsive to the fraction of inspired oxygen and the peak inspiratory pressure ventilator settings. A tested oxygenation controller successfully reached the target oxygen saturation within 5 min. The carbon dioxide removal system integrates with commercial ventilator technology and mimics carbon dioxide generation, lung compliance, and airway resistance while providing an end-tidal carbon dioxide level that is responsive to changes in the tidal volume and respiratory rate settings. A test mechanical ventilator controller was able to regulate EtCO2 regardless of the starting value within 10 min. This highlights the system’s functionality and provides proof-of-concept demonstrations for how the hardware-in-loop test platforms can be used for evaluating closed-loop controller technologies.

Berard, David (ORCID:0000000322863846)↗

PANDEMIC: Occupancy driven predictive ventilation control to minimize energy consumption and infection risk

During the SARS-CoV-2 (COVID-19) pandemic, governments around the world have formulated policies requiring ventilation systems to operate at a higher outdoor fresh air flow rate for a sufficient time, which has led to a sharp increase in building energy consumption. Therefore, it is necessary to identify an energy-efficient ventilation strategy to reduce the risk of infection. In this study, we developed an occupant-number-based model predictive control (OBMPC) algorithm for building ventilation systems. First, we collected the occupancy and Heating, ventilation, and air conditioning system (HVAC) data from March to July 2021. Then, four different models (Auto regression moving average-based multilayer perceptron (ARMA_MLP), Recurrent neural networks (RNN), Long short-term memory networks (LSTM), and Nonhomogeneous Markov with change points detection (NH_Markov)) were used to predict the number of room occupants from 15 min to 24 h ahead with an interval output. We found that each model could predict the number of occupants with 85% accuracy using a one-person offset. Furthermore, the accuracy of 15 min of the ahead prediction could reach 95% with a one-person offset, but none of them could track abrupt changes. The occupancy prediction results were used to calculate the ventilation demand using the Wells-Riley equation, and the upper bound can maintain an infection risk lower than 2% for 93% of the day. This OBMPC model could reduce the coil load by 52.44% and shift the peak load by 3 h up to 5 kW compared with 24 × 7 h full outdoor air (OA) system when people wear masks in the space. The occupancy prediction uncertainty could cause a 9% to 26% difference in demand ventilation, a 0.3°C to 2.4°C difference in zone temperature, a 28.5% to 44.5% difference in outdoor airflow rate, and a 10.7% to 28.2% difference in coil load.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Analysis of Frost Prevention for Heat Recovery Ventilation in an Arctic Facility

Sub-Arctic environments present a unique challenge for the continuous operation of mechanical ventilation systems in occupied buildings where cold temperatures create complications for maintaining adequate air quality, efficiency, and system operability. Heat recovery ventilation is most difficult at the coldest temperatures, when there is the greatest availability to transfer heat between airstreams, due to the potential for frost accumulation in the exhaust airstream. Frost limits heat transfer and creates the potential for subsequent blockage of airflow. A successful frost prevention strategy is necessary to ensure that recovery ventilation systems function in locations with a large amount of annual heating degree days. Commonly, this is achieved by preheating outdoor air above freezing temperatures via airflow through a glycol-water mix hydronic coil before heat exchange occurs. Preheating the outdoor air proactively inhibits frost formation but is associated with a penalty to recovery efficiency. A commercial-scale heat recovery ventilator in a facility in Fairbanks, Alaska was analyzed for sensible recovery effectiveness and exhaust temperature at different winter conditions. The system utilized the common defrost strategy of preheating the air above-freezing with a static temperature control scheme. The heat transfer efficiency of the recovery ventilator was observed to be poor at various winter conditions with elevated exhaust temperatures indicating lost heat recovery effectiveness. Using prior findings on strategies for sub-freezing temperatures along with observed field conditions it was determined that a dynamic relationship between the coil and the exterior conditions would reduce the energy required to preheat the air and allow the heat exchanger to maximize effectiveness due to temperate difference. This reduction in preheated temperature of the air is achieved by modulating the temperature of the coil to keep the discharge air stream above a certain dewpoint temperature threshold, likely leading to energy savings for other sub-Arctic facilities using this frost control strategy.

ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATION↗

Mechanical Ventilation and Indoor Air Quality in Recently Constructed U.S. Homes in Marine and Cold-Dry Climates Data from Building America Project

Data were collected to characterize whole-house mechanical ventilation (WHMV) and indoor air quality (IAQ) in 55 homes in the Marine climate of Oregon and Cold-Dry climate of Colorado in the U.S. Sixteen homes were monitored for two weeks, with and without WHMV operating. Ventilation airflows; airtightness; time-resolved CO2, PM2.5 and radon; and time-integrated NO2, NOX and formaldehyde were measured. Participants provided information about IAQ-impacting activities, perceptions and ventilation use. All homes had operational cooktop ventilation and bathroom exhaust. Thirty homes had equipment that could meet the ASHRAE 62.2-2010 standard with continuous or controlled runtime and 34 had some WHMV operating as found. Thirty-five of 46 participants with WHMV reported they did not know how to operate it, and only half of the systems were properly labeled. Two-week homes had lower formaldehyde, radon, CO2, and NO (NOX-NO2) when operated with WHMV; and also had faster PM2.5 decays following indoor emission events. Overall IAQ satisfaction was similar in Oregon and Colorado, but more Colorado participants (19 vs. 3%) felt their IAQ could be improved and more reported dryness as a problem (58 vs. 14%). The collected data indicate that there are benefits of operating WHMV, even when continuous use may not be needed because outdoor pollutant concentrations are low and indoor sources do not present substantial challenges.

air quality↗

Benefits assessment of cool skin and ventilated cavity skin: Saving energy and mitigating heat and grid stress

This study assessed the energy-saving and climate-adaptive potential of cool skin and ventilated cavity skin facade technologies in Seoul's high-rise apartment buildings. We created weather scenarios for historical, mid-term future, and long-term future conditions using Coordinated Regional Downscaling EXperiment (CORDEX) method. Building energy simulations were conducted on a South Korean high-rise apartment model to evaluate their performance under different weather conditions. The results indicate that cool skin and ventilated cavity skin technologies can save cooling energy during summers but lead to heating energy penalties in winters. Ventilated cavity skin outperforms cool skin, offering better cooling energy savings and reduced heating penalties. Combining both technologies yields the highest overall energy savings, with 7 %, 9 %, and 10 % cooling energy savings for cool skin, ventilated cavity skin, and the combined package, respectively. However, cool skin increases heating energy consumption by 5 %, while ventilated cavity skin has minimal impact on heating energy. These envelope technologies also reduce peak electricity demand by at least 5 %, 8 %, and 9 %, respectively. They contribute to heat stress reduction, enhance resilience, and decrease extreme heat risks for occupants during power outages by at least 18 % under various weather conditions. Considering the prevalence of aging high-rise apartments in South Korea, adopting these envelope renovation strategies can effectively reduce cooling loads, enhance thermal comfort, and boost resilience under future climates, while avoiding costly reconstruction.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Development of Advanced Smart Ventilation Controls for Residential Applications

This study examined the use of zoned ventilation systems using a coupled CONTAM/EnergyPlus model for new California dwellings. Several smart control strategies were developed with a target of halving ventilation-related energy use, largely through reducing dwelling ventilation rates based on zone occupancy. The controls were evaluated based on the annual energy consumption relative to continuously operating non-zoned, code-compliant mechanical ventilation systems. The systems were also evaluated from an indoor air quality perspective using the equivalency approach, where the annual personal concentration of a contaminant for a control strategy is compared to the personal concentration that would have occurred using a continuously operating, non-zoned system. Individual occupant personal concentrations were calculated for the following contaminants of concern: moisture, CO2, particles, and a generic contaminant. Zonal controls that saved energy by reducing outside airflow achieved typical reductions in ventilation-related energy of 10% to 30%, compared to the 7% savings from the unzoned control. However, this was at the expense of increased personal concentrations for some contaminants in most cases. In addition, care is required in the design and evaluation of zonal controls, because control strategies may reduce exposure to some contaminants, while increasing exposure to others.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Optimizing Ventilation Using Low-Cost Sensors to Improve Health, Safety, and Energy Efficiency

Air is the primary carrier of hazards within a space, whether it be hazardous byproducts of laboratory research activities or airborne pathogens. As a result, building ventilation is a primary defense against unseen airborne hazards. Critical laboratory facilities require effective mitigation of exposure to research-related, airborne hazards, providing a proving ground for effective ventilation strategies that optimize safety of occupants and reduce energy use. The heart of smart laboratory building operation is dynamic, analytics-based ventilation, which requires an in-depth intimate knowledge of building environmental conditions achieved through contaminant-detection systems. Unfortunately, currently many contaminant-detection solutions are expensive, elaborate systems that raise barriers for building managers. Through the successful deployment of a novel low-cost, modular sensor technology, we have developed a demand-control ventilation protocol effective in improving safety and reducing energy in critical laboratory environments. In this article, we will highlight best practices and lessons learned through this deployment that can be applied beyond laboratories. This article describes a low-cost sensor to support providing a safe, healthy building environment and reduce energy use through effective and efficient ventilation.

dynamic management of indoor air quality↗

Experimental evaluation of respiratory droplet spread to rooms connected by a central ventilation system

This article presents results from an experimental study to ascertain the transmissibility of the SARS-CoV-2 virus between rooms in a building that are connected by a central ventilation system. Respiratory droplet surrogates made of mucus and virus mimics were released in one room in a test building and measurements of concentration levels were made in other rooms connected via the ventilation system. The paper presents experimental results for different ventilation system configurations, including ventilation rate, filtration level (up to MERV-13), and fractional outdoor air intake. The most important finding is that respiratory droplets can and do transit through central ventilation systems, suggesting a mechanism for viral transmission (and COVID-19 specifically) within the built environment in reasonable agreement with well-mixed models. We also find the deposition of these droplets on room walls to be negligibly small. Furthermore, the energy use impact of the different configuration settings is also quantified to help inform intelligent building operation that can simultaneously address energy use and occupant health.

60 APPLIED LIFE SCIENCES↗

Super-relaxed myosins contribute to respiratory muscle hibernation in mechanically ventilated patients

Patients receiving mechanical ventilation in the intensive care unit (ICU) frequently develop contractile weakness of the diaphragm. Consequently, they may experience difficulty weaning from mechanical ventilation, which increases mortality and poses a high economic burden. Because of a lack of knowledge regarding the molecular changes in the diaphragm, no treatment is currently available to improve diaphragm contractility. We compared diaphragm biopsies from ventilated ICU patients (N= 54) to those of non-ICU patients undergoing thoracic surgery (N= 27). By integrating data from myofiber force measurements, x-ray diffraction experiments, and biochemical assays with clinical data, we found that in myofibers isolated from the diaphragm of ventilated ICU patients, myosin is trapped in an energy-sparing, super-relaxed state, which impairs the binding of myosin to actin during diaphragm contraction. Studies on quadriceps biopsies of ICU patients and on the diaphragm of previously healthy mechanically ventilated rats suggested that the super-relaxed myosins are specific to the diaphragm and not a result of critical illness. Exposing slow- and fast-twitch myofibers isolated from the diaphragm biopsies to small-molecule compounds activating troponin restored contractile force in vitro. These findings support the continued development of drugs that target sarcomere proteins to increase the calcium sensitivity of myofibers for the treatment of ICU-acquired diaphragm weakness.

Cell Biology↗