In this AVF Podcast: Behind-The-Scenes ICU Stories episode, Dr Daren Heyland shares key takeaways from large-scale randomised trials on critical care nutrition led by him and published in the last year, a culmination of his impressive career. Dr Heyland is a Professor of Medicine and Epidemiology at Queen’s University, Kingston, Ontario Canada.  He is trained in internal medicine, critical care medicine, and clinical epidemiology.  He currently serves as the Director of the Clinical Evaluation Research Unit at the Kingston General Hospital.  Overall, Dr Heyland has published approximately 450 peer-reviewed papers, raised more than $120 million in external grant support, and given more than 350 international presentations.

Issues discussed in this interview:

·         What inspired Dr Heyland to do research in nutrition in critical illness

·         The RE-ENERGIZE trial on enteral glutamine for burn injuries (NEJM 2022) 

·         The SUSTAIN CSX trial on high-dose selenium for cardiac surgery (JAMA Surgery 2023) 

·         The LOVIT trial on intravenous vitamin C for sepsis (NEJM 2022) 

·         The EFFORT Protein trial on higher protein dosing for critical illness (Lancet 2023) 

·         Future areas for research in nutrition in critical illness? 

·         Thoughts on clinical trial designs for the future

·         Reflections on Dr Heyland’s life’s work 

Selected further reading:

1.       Heyland DK, Wibbenmeyer L, Pollack JA, et al. A randomized trial of enteral glutamine for treatment of burn injuries. N Engl J Med 2022;387:1001-1010.

2.       Stoppe C, McDonald B, Meybohm P, et al. Effect of high-dose selenium on postoperative organ dysfunction and mortality in cardiac surgery patients: the SUSTAIN CSX randomized clinical trial. JAMA Surg 2023;158:235-244.

3.       Lamontagne F, Masse MH, Menard J, et al. Intravenous vitamin C in adults with sepsis in the intensive care unit. N Engl J Med 2022;386:2387-2398.

4.       Heyland DK, Patel J, Compher C, et al. The effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicentre, pragmatic, registry-based randomised trial. Lancet.2023;401:568-576.

5.       Lee ZY, Ortiz-Reyes L, Lew CCH, et al. Intravenous vitamin C monotherapy in critically ill patients: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis. Ann Intensive Care 2023;13:14.

The AVF Podcast: ICU Tips & Tricks invites colleagues to share anything and everything on how they deal with various clinical situations. Expect discussions on how experts personalise evidence-based medicine for the patient at the bedside.

In this episode, Professor Hodgson discusses the findings and implications of the landmark TEAM study on early active mobilisation during mechanical ventilation in the ICU, which was published in the New England Journal of Medicine in November 2022. Professor Hodgson is the Head of the Division of Clinical Trials and Cohort Studies in the School of Public Health and Preventive Medicine and Deputy Director of the Australian and New Zealand Intensive Care-Research Centre at Monash University, a specialist ICU physiotherapist at The Alfred, and the lead author of the TEAM study.
 
Issues discussed in this interview:
·         Prevalence and impact of ICU-acquired weakness
·         Rationale, methods, and findings of the TEAM study 
·         Comparisons with other studies
·         Recommended timing and intensity of mobilisation in the ICU in 2023
·         Future research
 

Selected further reading:

1.       TEAM Study Investigators and the ANZICS Clinical Trials Group, Hodgson CL, Bailey M, et al. Early active mobilization during mechanical ventilation in the ICU. N Engl J Med 10;387:1747-1758.
2.       Puthucheary ZA, Rawal J, McPhail M, et al. Acute skeletal muscle wasting in critical illness. JAMA 2013 16;310:1591-1600.
3.       Hermans G, Van Mechelen H, Clerckx B, et al. Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis. Am J Respir Crit Care Med 2014;190:410-420.
4.       Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 373:1874-1882.
5.       Patel BK, Wolfe KS, Patel SB, et al. Effect of early mobilisation on long-term cognitive impairment in critical illness in the USA: a randomised controlled trial. Lancet Respir Med 2023 Jan 20:S2213-2600(22)00489-1. Epub ahead of print.

In this AVF Podcast: ICU Tips & Tricks episode, Professor Professor Laffey discusses the findings and implications of the landmark WEAN SAFE study on the epidemiology and outcomes of weaning from invasive mechanical ventilation across 50 countries, which was published in The Lancet Respiratory Medicine in January 2023. Dr Laffey is Professor of Anaesthesia and Intensive Care Medicine at the School of Medicine of the National University of Ireland, a Consultant in Anaesthesia and Intensive Care Medicine at Galway University Hospitals, and corresponding author of the WEAN SAFE study.

Issues discussed in this interview:

·         Key findings of the WEAN SAFE study

·         Implications of delaying weaning in patients on invasive mechanical ventilation

·         Rewards and challenges of performing large multi-country studies

Selected further reading:

1.       Pham T, Heunks L, Bellani G, et al. Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study. Lancet Respir Med. 2023 Jan 20:S2213-2600(22)00449-0. Epub ahead of print.

In this AVF Podcast: Behind-The-Scenes ICU Stories episode, Dr Andrew Li discusses MOSAICS II, the largest ever study on sepsis in Asian ICUs, and one that was completed before the COVID-19 pandemic. Dr Li is the lead author of the MOSAICS II study, and a consultant respiratory physician and intensivist from Singapore’s National University Hospital and Woodlands Health. 

Issues discussed in this interview: 

·       Key findings of the MOSAICS II study 

·       Brief comparison with the MOSAICS I study published in 2011

·       Challenges and rewards from multinational research collaboration

Selected further reading:

1.       Li A, Ling L, Qin H, et al. Epidemiology, management, and outcomes of sepsis in ICUs among countries of differing national wealth across Asia. Am J Respir Crit Care Med 2022;206:1107-1116.

2.       Phua J, Koh Y, Du B, et al. Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study. BMJ 2011;342:d3245.

3.       Vincent JL, Sakr Y, Singer M, et al. Prevalence and outcomes of infection among patients in intensive care units in 2017. JAMA 2020;323:1478-1487. 

4.       Phua J, Faruq MO, Kulkarni AP, et al. Critical care bed capacity in Asian countries and regions. Crit Care Med 2020;48:654-662.

In this AVF Podcast: Behind-The-Scenes ICU Stories episode, Professor Carolyn Calfee shares her journey on and discusses the science behind precision medicine in the acute respiratory distress syndrome (ARDS) and intensive care. Dr Calfee is Professor in Residence of Medicine and Anesthesia at the University of California, San Francisco (UCSF), where she attends in the intensive care units (ICUs) at Moffitt-Long Hospital. Her primary academic focus is the prevention, diagnosis, prognosis, and treatment of ARDS, and she is a key international leader with multiple high impact publications on molecular phenotyping of ARDS and precision medicine in the ICU.

Issues discussed in this interview:

•         What precision medicine is

•         The rationale for precision medicine in ARDS

•         How Dr Calfee entered this field of research 

•         Selected landmark studies that reflect the potential of precision medicine in ARDS

•         Challenges to overcome

•         Implications for practising clinicians today

Selected further reading:

1.       Beitler JR, Thompson BT, Baron RM, et al. Advancing precision medicine for acute respiratory distress syndrome. Lancet Respir Med 2022;10:107-20.

2.       Bos LDJ, Artigas A, Constantin JM, et al. Precision medicine in acute respiratory distress syndrome: workshop report and recommendations for future research. Eur Respir Rev 2021;30.

3.       Reddy K, Sinha P, O'Kane CM, Gordon AC, Calfee CS, McAuley DF. Subphenotypes in critical care: translation into clinical practice. Lancet Respir Med 2020;8:631-43.

4.       Sinha P, Delucchi KL, Thompson BT, et al. Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study. Intensive Care Med 2018;44:1859-69.

5.       Calfee CS, Delucchi KL, Sinha P, et al. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med 2018;6:691-8.

6.       Famous KR, Delucchi K, Ware LB, et al. Acute respiratory distress syndrome subphenotypes respond differently to randomized fluid management strategy. Am J Respir Crit Care Med 2017;195:331-8.

7.       Calfee CS, Delucchi K, Parsons PE, et al. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med 2014;2:611-20.

In this AVF Podcast: ICU Tips & Tricks episode, Professor Paul Young discusses the evidence behind oxygen targets in the intensive care unit (ICU). Professor Young is Deputy Director and Intensive Care Programme Director at the Medical Research Institute of New Zealand, Co-Clinical Lead of the ICU at Wellington Hospital, and the Medical Director of Wakefield Hospital in Wellington, New Zealand. His high-impact studies include the SPLIT trial (JAMA 2015), the HEAT trial (N Engl J Med 2015), the ICU-ROX trial (N Engl J Med 2020), the PEPTIC trial (JAMA 2020), and the VITAMINS trial (JAMA 2020).

Issues discussed in this interview:

• The potential risks of hyperoxia in ICU patients
• Oxygenation targets in the general ICU population as well as for specific patient subsets
• The implications of studies such as ICU-ROX (2020), HOT-ICU (2021), and the ongoing Mega-ROX trial
• Strategies (and the limitations of knowledge) for fine-tuning targets in complicated populations 

For more about the Mega-ROX trial, please visit:

1.     https://www.anzics.com.au/current-active-endorsed-research/mega-rox/

2.    https://www.youtube.com/watch?v=dMOrOPahXTw

3.    https://ccr.cicm.org.au/journal-editions/2022/june/24/original-articles/article-8

Work cited:

1.       Young PJ, Hodgson CL, Rasmussen BS. Oxygen targets. Intensive Care Med 2022;48:732-5.

2.       The ICU-ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group et al. Conservative oxygen therapy during mechanical ventilation in the ICU. N Engl J Med 2020;382:989-98.

3.       Schjorring OL, Klitgaard TL, Perner A, et al. Lower or higher oxygenation targets for acute hypoxemic respiratory failure. N Engl J Med 2021;384:1301-11.

4.       Girardis M, Busani S, Damiani E, et al. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the Oxygen-ICU randomized clinical trial. JAMA 2016;316:1583-9.

5.       Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet 2018;391:1693-705.

6.       Asfar P, Schortgen F, Boisrame-Helms J, et al. Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial. Lancet Respir Med 2017;5:180-90.

In this AVF Podcast: ICU Tips & Tricks episode, Dr Brenda Pun discusses how healthcare workers should look after family members and loved ones of critically ill patients. Dr Pun is an advanced practice nurse with a special interest in critical care, who serves as the Director of Data Quality at the Vanderbilt Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center. She is a key leader of the 2018 clinical practice guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility and Sleep Disruption in Adult Patients in the ICU (PADIS) and in the implementation of the ABCDEF bundle. Her research has focused on improving the care and outcomes of critically ill patients with a special emphasis on delirium, sedation, long-term outcomes and teamwork.

Issues discussed in this interview:

·         Impact of critical illness on family members and loved ones of patients in the ICU

·         Post-intensive care syndrome-family (PICS-F)

·         The ABCDEF bundle

·         Care for family members and loved ones in the ICU

·         Care for family members and loved ones after the ICU stay

·         Care for family members and loved ones of dying and deceased patients

·         COVID-19 and its impact on family members and loved ones of patients in the ICU

Work cited:

1.       Devlin JW, Skrobik Y, Gelinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med 2018;46:e825-e73.

2.       Davidson JE, Aslakson RA, Long AC, et al. Guidelines for family-centered care in the neonatal, pediatric, and adult ICU. Crit Care Med 2017;45:103-28.

3.       Pun BT, Balas MC, Barnes-Daly MA, et al. Caring for critically ill patients with the ABCDEF bundle: results of the ICU Liberation Collaborative in over 15,000 adults. Crit Care Med 2019;47:3-14.

4.       Pun BT, Badenes R, Heras La Calle G, et al. Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study. Lancet Respir Med 2021;9:239-50.

In this AVF Podcast: ICU Tips & Tricks episode, Professor Margaret Herridge discusses what patients and their loved ones go through after surviving ARDS and how we can help them. Dr. Herridge is a Professor in the Department of Medicine, a Senior Scientist in the Toronto General Hospital Research Institute, Director of the RECOVER Program/Grace RECOVER Program for Chronic Critical Illness, and co-lead (with Dr. Angela Cheung) of CANCOV (Canadian multi-centre 2-year follow-up of patients/caregivers after COVID-19). She has been the lead or co-lead on 5 publications in the New England Journal of Medicine and has published over 200 articles and book chapters on patient and caregiver outcomes after critical illness.

Issues discussed in this interview:

·         Long-term physical, cognitive, and psychological complications of ARDS and critical  
           illness
·         Evidence-based interventions to minimise such complications
·         Care for ARDS survivors and their loved ones

Work cited:

1.       Levine S, Nguyen T, Taylor N, et al. Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med 2008;358:1327-35.

2.       Puthucheary ZA, Rawal J, McPhail M, et al. Acute skeletal muscle wasting in critical illness. JAMA 2013;310:1591-600.

3.       Herridge MS, Cheung AM, Tansey CM, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 2003;348:683-93.

4.       Herridge MS, Tansey CM, Matte A, et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med 2011;364:1293-304.

5.       Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med 2013;369:1306-16.

6.       Needham DM, Davidson J, Cohen H, et al. Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders' conference. Crit Care Med 2012;40:502-9.

7.       Brummel NE, Girard TD, Pandharipande PP, et al. Prevalence and course of frailty in survivors of critical illness. Crit Care Med 2020;48:1419-26.

8.       Azoulay E, Resche-Rigon M, Megarbane B, et al. Association of COVID-19 acute respiratory distress syndrome with symptoms of posttraumatic stress disorder in family members after ICU discharge. JAMA 2022;327:1042-50.

9.       Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet 2021;397:220-32.

10.   Hermans G, Wilmer A, Meersseman W, et al. Impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive care unit. Am J Respir Crit Care Med 2007;175:480-9.

11.   Schaller SJ, Anstey M, Blobner M, et al. Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial. Lancet 2016;388:1377-88.

12.   Hughes CG, Mailloux PT, Devlin JW, et al. Dexmedetomidine or propofol for sedation in mechanically ventilated adults with sepsis. N Engl J Med 2021;384:1424-36.

13.   Goligher EC, Jonkman AH, Dianti J, et al. Clinical strategies for implementing lung and diaphragm-protective ventilation: avoiding insufficient and excessive effort. Intensive Care Med 2020;46:2314-26.

In this AVF Podcast: Behind-The-Scenes ICU Stories episode, Professor Jean-Louis Vincent paints his vision for the future of intensive care. Professor Vincent is Professor of intensive care medicine at the University of Brussels. He is Past-President of the World Federation of Societies of Intensive and Critical Care Medicine and the European Society of Intensive Care Medicine. He is the editor-in-chief of Critical Care, Current Opinion in Critical Care, and ICU Management & Practice, and member of the editorial boards of about 30 other journals. He has authored more than 1000 original articles, and his H index is 193.

Issues discussed in this interview:

• Critical care medicine outside the intensive care unit (ICU)
• Mixed versus medical or surgical ICU
• Multidisciplinary teams
• Protocolised versus personalised care with artificial intelligence
• Outcomes beyond mortality
• Telemedicine and pre-hospital care
• Humanity and diversity in medicine
• Noninvasive monitoring and extracorporeal organ support
• Passion and inspiration

 Work cited:

1. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med 2021;47:1181-247.
2. Alam N, Oskam E, Stassen PM, et al. Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial. Lancet Respir Med 2018;6:40-50.
3. Vincent JL. Antibiotic administration in the ambulance? Lancet Respir Med 2018;6:5-6.
4. Lane DJ, Wunsch H, Saskin R, et al. Association between early intravenous fluids provided by paramedics and subsequent in-hospital mortality among patients with sepsis. JAMA Netw Open 2018;1:e185845.
5. Ranieri VM, Brodie D, Vincent JL. Extracorporeal organ support: from technological tool to clinical strategy supporting severe organ failure. JAMA 2017;318:1105-6.
6. Mang S, Reyher C, Mutlak H, et al. Awake extracorporeal membrane oxygenation for COVID-19-induced acute respiratory distress syndrome. Am J Respir Crit Care Med 2022;205:847-51.