Indirect Calorimetry Critical in Identifying Early Hypometabolism and Late-Stage Hypermetabolism in Post-surgical Patients

Background: Indirect calorimetry (IC) is the gold-standard procedure for measuring resting energy expenditure (REE) in hospitalized patients. Predictive energy equations commonly use static variables and rarely account for changes in REE throughout hospitalization. We hypothesize that predictive equations are typically inaccurate in surgical intensive care unit (ICU) patients. More specifically, we hypothesize that predictive equations often overpredict measured resting energy expenditure (mREE) in early-stage critical illness and underpredict needs later in surgical ICU stay, leading to over-/under-feeding and associated complications. Method(s): This prospective observational trial enrolled surgical ICU patients who underwent emergent or urgent operations for abdominal trauma, perforated viscus, or ischemic bowel within 72 hours of their surgical procedure. Metabolic assessments were performed using the COSMED Q-NRG + Metabolic Monitor ventilator, mask, and canopy at regular intervals during and post ICU admission until hospital discharge. Measurements were categorized by post-surgical intervention ICU admission days 0-3, 4-7, 8-14, 15-21, and 22-28. Patients with multiple measurements taken during the same time interval were averaged. mREE reported in calories (kcal) per kilogram (kg) of admission body weight per day were compared in obese (BMI > 30 kg/m2) and non-obese (BMI < 30 kg/m2) subgroups. Compared to IC, the Mifflin St Jeor (MSJ) equation determined predicted REE using ICU admission anthropometrics. Data are reported as mean+/-standard error of the mean (SEM) and median (interquartile range), and a two-sided p-value of <0.05 was determined significant. Result(s): In total, 18 surgical ICU patients who contributed 47 IC measurements were included in the analysis (Table 1). Most measures were obtained within the first 7 days of post-surgical ICU admission (72%). mREE peaked between days 8-14 in obese and non-obese subgroups (20.6 vs 28.5 kcal/kg;p = 0.02) and was lowest during 0-3 days of post-surgical ICU admission in both groups. Across all 5-time intervals, average kcal/ kg ranged from 14.7-20.6 among obese patients and from 20.1-28.5 in non-obese counterparts (Table 2). Non-obese patients had higher mREE per kg of body weight than obese patients at all time points (Figure 1). MSJ over-predicted mREE during the first 7 days post ICU admission in non-obese patients and within the first 3 days in obese patients and underpredicted mREE in both groups thereafter. Conclusion(s): Equations such as MSJ over- and under-predict mREE in post-operative surgical ICU patients depending on the days elapsed since post-surgical ICU admission. ASPEN's current guideline recommendation of 12-25 kcal/kg may also underfeed post-surgical populations while 25 kcal/kg may not support hypermetabolism among non-obese patients seen in week 2 following post-surgical ICU admission. Alternatively, MSJ multiplied by a 1.2 activity factor may account for hypermetabolism during this time. Notably, non-obese patients experienced greater hypermetabolism than obese patients during week 2 which is consistent with our previously published data in mechanically ventilated COVID- 19 patients. Additionally, the striking dichotomy between the mREE of obese and non-obese patients at all post-surgical time points should be considered in the clinical care of patients. Ultimately, IC remains the gold-standard means of measuring REE and is a critical tool to capture the dynamic nature of energy requirements in post-surgical populations as weight-based and predictive equations continually fall short. (Table Presented).

Family experiences and perceptions of intensive care unit care and communication during the COVID-19 pandemic.

INTRODUCTION: In 2020, during the first wave of the COVID-19 pandemic in Melbourne, visitor access to acute hospitals including intensive care units (ICUs) was initially barred, followed by a limit of one person per patient for one hour per day. This study explores the care and communication experienced by family members of ICU patients during this time. METHODS: This qualitative descriptive study was conducted at an Australian quaternary hospital. Semistructured phone interviews were conducted using an aide-memoire designed to understand participants' experiences as family of a patient during this time. Interviews were recorded, transcribed, and thematically analysed. FINDINGS: Twenty family members of patients in the ICU participated. Three major themes were identified: 'impact of restricting visiting procedures', 'family experiences of communication', and 'care and support'. Inflexible visiting restrictions had a momentous impact on families. Participants objected to having to nominate only two people to visit during the admission and the short visiting time limit. Some family members suffered extreme stress and anxiety during their absence from the bedside. Additional challenges were experienced by rural families, visitors with disabilities, and the young children of patients who were excluded. Communication with clinicians varied. Telehealth was valued by some but not universally embraced. The relationship between staff members and families and involvement in decision-making were unaffected. CONCLUSION: Families experienced significant psychological distress from being separated from their critically ill relatives. Patient care and involvement in decision-making appeared to be unchanged, but communication with staff felt to be lacking. Better alternatives to face-to-face communication must be sought to limit the impact of family separation on mental health. Families are a key link between the patient and clinicians and often play a major role in patient support and recovery after discharge. There is an urgent need to support them and facilitate meaningful engagement despite the obstacles.

Allied health surge capacity in Australian intensive care units during the COVID-19 pandemic: A cross-sectional survey

Background: Based on the early international COVID-19 experience, it was anticipated that intensive care services and workforces in Australia would be placed under similar pressure. While surge capacity of medical and nursing workforces was estimated, little was known about baseline allied health staffing, making it difficult to estimate surge capacity and coordinate planning. Objectives: The purpose of this study was to (i) capture baseline allied health staffing levels in Australian adult intensive care units (ICUs) prior to the COVID-19 pandemic emergence in Australia and (ii) describe the allied health pandemic planning and surge response in Australian ICUs during the early waves of the pandemic. Methods: This was a cross-sectional, investigator-devised, prospective survey study. The survey was administered via the national chief allied health network to a convenience sample of senior ICU allied health clinicians at hospitals throughout Australia. Results: A total of 40 responses were received from tertiary and metropolitan hospitals;12 (30%) physiotherapists and eight (20%) occupational therapists were the most frequent respondents. Prior to the COVID-19 pandemic, 28 (70%) allied health respondents had a mean (interquartile range) of 1.74 (2.00) full-time equivalent staff designated to the ICU, where these ICUs had a mean of 21.53 (15.00) ventilator beds. Few respondents serviced their ICU on a referral-only basis and did not have dedicated ICU full-time equivalent (12;20%). Surge planning was mostly determined by discussion within the ICU, allied health department, and/or respective disciplines. This approach meant that allied health staffing and associated decision-making was ad hoc at a local level. Conclusions: The baseline rate of allied health coverage in Australian ICUs remains unknown, and the variability across allied health and within the specific disciplines is undetermined. Further research infrastructure to capture ICU allied health workforce data is urgently needed to guide future pandemic preparedness. © 2022 Australian College of Critical Care Nurses Ltd

Process Development and Manufacturing: A SUPPLY CHAIN CRISIS STORY: CULTURE BAG SHORTAGE ENFORCED VALIDATION OF AN ALTERNATIVE EXPANSION SYSTEM FOR CAR T CELLS

Background & Aim: The recent supply chain crisis highlights a need to establish alternative manufacturing (MFG) protocols ensuring continuity of existing and new cell therapy (CT) clinical trials. Our academic CT program, and likely others, experienced purchasing delays and restrictions caused by diversion of critical supplies to meet COVID-19- related research demands and/or reduced vendor capacity due to resource constraints, including attrition of skilled workforce. Mitigation strategies aimed at creating process redundancies overcome production challenges resulting from a scarcity of goods. Here, we validated an alternative ex vivo culture system to clinically MFG lentiviral vector (LV) modified CAR T cells due to limited availability of cell expansion culture bags for the Wave bioreactor, a critical unit of operation that we have used to successfully MFG thousands of gene-modified T cell products for 30+ clinical trials. Methods, Results & Conclusion: The disposable G-REX culture vessels were compatible and seamlessly integrated with our closed system platform. Mesothelin CAR T cells were manufactured in parallel via the G-REX or conventional Wave bioreactor using consented patient starting material. Critical quality attributes of the final T cell products, including viability, transduction efficiency, phenotype and function were assessed. Transduction efficiencies assessed by flow cytometry and/or molecular qPCR were lower in products generated in the G-REX compared to the wave using the same multiplicity of infection. However, at least 50-fold expansion was achieved, with cell viabilities greater than 90% and with comparable cellular phenotypes. The Meso CAR T cells generated by either process were capable of eliciting CAR-mediated cytotoxicity and effector cytokine production. Strikingly, 2-4 billion T cells were harvested from a starting seed number of just 50 million T cells in the 1L G-REX, which may be sufficient to meet most protocol- specified cell therapy doses, suggesting that a full apheresis collection may not be needed. Notably, this process required just 1/3 of the starting material, 1/5 of the media and decreased manual effort through culture duration compared to the Wave. Additionally, the reduced reliance on specialized capital equipment combined with a small footprint enables simultaneous MFG of several immunotherapy products. These advantages propose consideration in replacement of current expansion platform as well as validating an alternative process for MFG CAR T cells.