Weaning Algorithm for Mechanical VEntilation

Respiratory Insufficiency Clinical Trial

— WAVE  

Official title:

Weaning Algorithm for Mechanical VEntilation (WAVE Study): A Randomised Control Trial Comparing an Open-loop Decision Support System Versus Routine Care for Weaning From Mechanical Ventilation in the Cardiothoracic Intensive Care Unit

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03697785
• Other study ID #: REC Reference: 18/LO/0282
• Secondary ID: 239144
• Status: Recruiting
• Phase: N/A
• Start date: September 24, 2018
• Est. completion date: October 1, 2021

Study information

• Verified date: October 2018
• Source: Royal Brompton & Harefield NHS Foundation Trust
• Contact: Brijesh V Patel, MBBS MRCP FRCA FFICM PhD
• Phone: +44 (0)20 7352 8121
• Email: brijesh.patel[@]imperial.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To compare the duration of mechanical ventilation and the weaning period between two groups of patients managed with either Standard Care or with mechanical ventilation adjusted according to the Beacon Caresystem, in patients receiving mechanical ventilation for more than 24 hours

Description:

Patients admitted to the intensive care unit typically receive invasive mechanical ventilatory support when they are critically ill. Whilst mechanical ventilation is a life-saving intervention, it can also lead to deleterious consequences and cause lung damage (known as ventilator-associated lung injury) if not implemented carefully. Hence, reducing the duration of mechanical ventilation should reduce complications such as ventilator-associated lung injury, ventilator-acquired pneumonia, respiratory and skeletal muscle wasting, and patient discomfort, leading to decreasing mortality and economic costs etc. Importantly, prolonged weaning perpetuates these complications which further increase the duration of mechanical ventilation thereby creating a viscous cycle leading to greater morbidity and mortality.

The availability and education of intensive care unit (ICU) staff are important considerations in minimizing the duration of mechanical ventilation through weaning protocols. It is common practice that the attending physician decides upon patient's therapy and ventilatory management according to recommendations. This usually occurs as part of medical rounds. In addition, nurses often manage the weaning of patients from mechanical ventilation either by following attending physicians' instructions or local guidelines protocols. Such protocol-directed, nurse-driven weaning has been shown to reduce the duration of mechanical ventilation. However, it has been shown that the quantity and quality of nursing are important factors if duration is to be reduced.

Several decision support systems have been developed to help select optimal mechanical ventilator strategies. Those finding their way into routine clinical practice have typically been based on clinical guidelines or rules rather than detailed physiological description of the individual patient. A recent Cochrane review of weaning trials with these systems concluded that use of these systems may reduce duration of weaning, but pointed out that many of these trials are based on patients that are 'simple to wean'. Such patients are usually less complex, without lung pathology, and ventilated for less than 48 hours. However, there is a need to develop and validate protocolised systems that utilize a more detailed physiological description of individual patients to aid in the management of complex patients ventilated for longer durations.

The Beacon Caresystem is a model-based decision support system using mathematical models tuned to the individual patient's physiology to advise on appropriate ventilator settings. Personalised approaches using individual patient description may be particularly advantageous in complex patients, including those who are difficult to mechanically ventilate and wean; precisely those where previous systems have not been sufficiently evaluated. The Beacon Caresystem is a commercial version of the system previously known as INVENT, which has been retrospectively evaluated in post-operative cardiac patients and patients with severe lung disease, and prospectively evaluated in advising on the correct level of inspiratory oxygen. Furthermore, studies are near completion showing that the system provides safe and appropriate advice on inspired oxygen, respiratory frequency, tidal volume, pressure support/control and positive end expiratory pressure (PEEP) in a wide variety of patients ranging from patients with severe respiratory failure to patients close to extubation (unpublished data). However, previous and ongoing studies with the Beacon Caresystem have focused on safety and efficacy of advice under limited time periods, and have not focused on weaning from mechanical ventilation.

The core of the Beacon Caresystem is a set of physiological models including pulmonary gas exchange, acid-base chemistry, lung mechanics, and respiratory drive. The Beacon Caresystem tunes these models to the individual patient such that they describe accurately current measurements. Once tuned, the models are used by the system to simulate the effects of changing ventilator settings. The results of these simulations are then used to calculate the clinical benefit of changing ventilator settings by balancing the competing goals of mechanical ventilation. For example, an increased inspiratory volume will reduce an acidosis of the blood while detrimentally increasing lung pressure. Appropriate ventilator settings therefore imply a balance between the preferred value of pH weighted against the preferred value of lung pressure. A number of these balances exist, and the system weighs these, calculating a total score for the patient for any possible ventilation strategy. The system then calculates advice as to changes in ventilator settings so to as improve this score. The Beacon Caresystem functions as an "open loop" system. This means that the advice provided by the system is presented to the clinician. The ventilator settings are then changed by the clinician, and the patient's physiological response to these changes is automatically used by the system to re-tune the models and repeat the process of generating new advice.

In calculating appropriate advice, selecting the correct level of positive end expiratory pressure (PEEP) is particularly challenging. The nature of the challenge is however, very different depending upon the presence or type of lung abnormality, and the function of the heart. Patients with severe lung abnormalities such as acute respiratory distress syndrome (ARDS), which often result in small, stiff lungs, are often in control ventilation mode with little or no spontaneous breathing. For these patients, PEEP is often increased to try to recruit units of the lung which are collapsed. This can be difficult, as increasing PEEP may result in elevated lung pressure and hence an increased the risk of lung injury, incomplete expiration and air trapping, and haemodynamic compromise, especially in those with heart failure.

Patients in support ventilation modes have some degree of spontaneous breathing, and the correct selection of PEEP therefore includes different criteria. It is important that these patients be weaned as quickly as possible, and PEEP is reduced as part of that process. If the setting of PEEP is too low, there is a risk of increased resistance to airflow with added respiratory work and consequent risk of respiratory muscle fatigue. If the patient has intrinsic PEEP due to dynamic hyperinflation, reducing PEEP below the level of intrinsic PEEP would also cause increased inspiratory threshold load on the respiratory muscles, and potential muscle fatigue. If PEEP is too high the respiratory muscle fibres may be shortened reducing their pressure generating capacity and endurance thus increasing the risk of respiratory muscle fatigue. Changing pressure support may help to work against an additional workload, as in cases of increased resistance or autoPEEP, whilst correct PEEP may counter the additional load.

The above factors are taken into account by the physiological models of the Beacon Caresystem, and patient specific advice is also provided on PEEP. In addition to providing advice on changing individual ventilator settings, the system also advises on when measurement of arterial blood gas is necessary, when it is important to change ventilator mode, and when a spontaneous breathing test is passed, and as such extubation should be considered.

However, previous and ongoing studies with the Beacon Caresystem have focused on safety and efficacy of advice under limited time periods, and have not focused on weaning from mechanical ventilation. A current study is underway in a French hospital (Clinical Trials number: NCT02842944), and at a UK hospital (IRAS 226610), to assess the benefit of the Beacon Caresystem in general medical intensive care patients. However, as mechanical ventilation therapy can vary with different patient populations it is important that investigation of the effects of use of the Beacon system be studied in numerous different clinical situations. In contrast to other studies, this study will investigate the effects of the Beacon Caresystem in ICU patients with primary cardio-thoracic disease, with these patients representing a substantial sub group of all ICU patients worldwide.

The purpose of this study is to compare mechanical ventilation following advice from the Beacon Caresystem to that of routine care in cardio-thoracic ICU patients from the start of requiring invasive mechanical ventilation until ICU discharge or death. The Beacon Caresystem will be compared to routine care to investigate whether use of the system results in similar care or reduced time for weaning from mechanical ventilation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 286
• Est. completion date: October 1, 2021
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Patient remains on mechanical ventilation at 24 hours following intubation.

• Age > 18 years

• Patient consent or, in the case that the patient is unable, advice from the next of kin or treating physician following understanding and acceptance of oral and written information describing the study.

Exclusion criteria:

• The absence of an arterial catheter for blood sampling at study start.

• Mechanical ventilation initiated for more than 48 hours.

• Medical history of home mechanical ventilation which may lead to prolonged stay in the ICU, including long term oxygen therapy and non-invasive ventilation not associated with sleep apnoea.

• Patients mechanically ventilated in a ventilator mode, and by a ventilator not supported by the Beacon Caresystem on screening.

• Respiratory failure likely requiring extracorporeal support.

• Severe cardiogenic shock likely requiring extracorporeal support.

• Severe isolated right heart failure.

• Head trauma or other conditions where intra-cranial pressure may be elevated and tight regulation of arterial CO2 level is paramount.

• Primary (non-overdose related) neurological patients (Glasgow coma score <10, neurologic damage with limited prognosis, stroke hemiplegia).

• End stage liver disease.

• Repeated ICU admission within same hospital admission and/or likely to have prolonged ICU stay with mechanical ventilation (>21 days)

• Pregnancy.

Related Conditions & MeSH terms

• Critical Care
• Intensive Care (ICU) Myopathy
• Mechanical Ventilation Complication
• Pulmonary Valve Insufficiency
• Respiration, Artificial
• Respiratory Insufficiency

Intervention

Device:
• Beacon Care System
Beacon has been developed by Mermaid Care in Denmark. BEACON is a critical care ventilation assist system (http://beaconcaresystem.com/beacon-5/), which potentially enables better ventilation strategies and a more efficient patient care workflow. As an add-on to standard ventilation systems it provides ventilation recommendations 24/7 based on non-stop, personalised monitoring/diagnostics of patients. Based on unique mathematical algorithms and physiological models, it recommends changes in ventilation settings, supporting the critical decision-making processes.

Locations

Country	Name	City	State
United Kingdom	Royal Brompton Hospital	London
United Kingdom	Harefield Hospital	Uxbridge

Sponsors (4)

Lead Sponsor	Collaborator
Royal Brompton & Harefield NHS Foundation Trust	Aalborg University, Imperial College London, Mermaid Care A/S

Country where clinical trial is conducted

United Kingdom, 

References & Publications (28)

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Allerød C, Rees SE, Rasmussen BS, Karbing DS, Kjaergaard S, Thorgaard P, Andreassen S. A decision support system for suggesting ventilator settings: retrospective evaluation in cardiac surgery patients ventilated in the ICU. Comput Methods Programs Biomed. 2008 Nov;92(2):205-12. doi: 10.1016/j.cmpb.2008.07.001. — View Citation

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Blackwood B, Alderdice F, Burns K, Cardwell C, Lavery G, O'Halloran P. Use of weaning protocols for reducing duration of mechanical ventilation in critically ill adult patients: Cochrane systematic review and meta-analysis. BMJ. 2011 Jan 13;342:c7237. doi: 10.1136/bmj.c7237. Review. — View Citation

Corner EJ, Soni N, Handy JM, Brett SJ. Construct validity of the Chelsea critical care physical assessment tool: an observational study of recovery from critical illness. Crit Care. 2014 Mar 27;18(2):R55. doi: 10.1186/cc13801. — View Citation

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Danckers M, Grosu H, Jean R, Cruz RB, Fidellaga A, Han Q, Awerbuch E, Jadhav N, Rose K, Khouli H. Nurse-driven, protocol-directed weaning from mechanical ventilation improves clinical outcomes and is well accepted by intensive care unit physicians. J Crit Care. 2013 Aug;28(4):433-41. doi: 10.1016/j.jcrc.2012.10.012. Epub 2012 Dec 21. — View Citation

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Herridge MS, Tansey CM, Matté A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM; Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011 Apr 7;364(14):1293-304. doi: 10.1056/NEJMoa1011802. — View Citation

Karbing DS, Allerød C, Thomsen LP, Espersen K, Thorgaard P, Andreassen S, Kjærgaard S, Rees SE. Retrospective evaluation of a decision support system for controlled mechanical ventilation. Med Biol Eng Comput. 2012 Jan;50(1):43-51. doi: 10.1007/s11517-011-0843-y. Epub 2011 Nov 22. — View Citation

Karbing DS, Allerød C, Thorgaard P, Carius AM, Frilev L, Andreassen S, Kjaergaard S, Rees SE. Prospective evaluation of a decision support system for setting inspired oxygen in intensive care patients. J Crit Care. 2010 Sep;25(3):367-74. doi: 10.1016/j.jcrc.2009.12.013. Epub 2010 Feb 10. — View Citation

Lellouche F, Mancebo J, Jolliet P, Roeseler J, Schortgen F, Dojat M, Cabello B, Bouadma L, Rodriguez P, Maggiore S, Reynaert M, Mersmann S, Brochard L. A multicenter randomized trial of computer-driven protocolized weaning from mechanical ventilation. Am J Respir Crit Care Med. 2006 Oct 15;174(8):894-900. Epub 2006 Jul 13. — View Citation

MacIntyre NR, Cheng KC, McConnell R. Applied PEEP during pressure support reduces the inspiratory threshold load of intrinsic PEEP. Chest. 1997 Jan;111(1):188-93. — View Citation

Mador MJ. Respiratory muscle fatigue and breathing pattern. Chest. 1991 Nov;100(5):1430-5. Review. — View Citation

McAuley DF, Laffey JG, O'Kane CM, Cross M, Perkins GD, Murphy L, McNally C, Crealey G, Stevenson M; HARP-2 investigators; Irish Critical Care Trials Group. Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial: study protocol for a randomized controlled trial. Trials. 2012 Sep 17;13:170. doi: 10.1186/1745-6215-13-170. — View Citation

Parry SM, Denehy L, Beach LJ, Berney S, Williamson HC, Granger CL. Functional outcomes in ICU – what should we be using? – an observational study. Crit Care. 2015 Mar 29;19:127. doi: 10.1186/s13054-015-0829-5. — View Citation

Powers SK, Wiggs MP, Sollanek KJ, Smuder AJ. Ventilator-induced diaphragm dysfunction: cause and effect. Am J Physiol Regul Integr Comp Physiol. 2013 Sep;305(5):R464-77. doi: 10.1152/ajpregu.00231.2013. Epub 2013 Jul 10. Review. — View Citation

Puthucheary ZA, McNelly AS, Rawal J, Connolly B, Sidhu PS, Rowlerson A, Moxham J, Harridge SD, Hart N, Montgomery HE. Rectus Femoris Cross-Sectional Area and Muscle Layer Thickness: Comparative Markers of Muscle Wasting and Weakness. Am J Respir Crit Care Med. 2017 Jan 1;195(1):136-138. doi: 10.1164/rccm.201604-0875LE. — View Citation

Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, Hopkinson NS, Phadke R, Dew T, Sidhu PS, Velloso C, Seymour J, Agley CC, Selby A, Limb M, Edwards LM, Smith K, Rowlerson A, Rennie MJ, Moxham J, Harridge SD, Hart N, Montgomery HE. Acute skeletal muscle wasting in critical illness. JAMA. 2013 Oct 16;310(15):1591-600. Erratum in: JAMA. 2014 Feb 12;311(6):625. Padhke, Rahul [corrected to Phadke, Rahul]. — View Citation

Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA. 1999 Jul 7;282(1):54-61. — View Citation

Rees SE, Allerød C, Murley D, Zhao Y, Smith BW, Kjaergaard S, Thorgaard P, Andreassen S. Using physiological models and decision theory for selecting appropriate ventilator settings. J Clin Monit Comput. 2006 Dec;20(6):421-9. Epub 2006 Sep 15. — View Citation

Rees SE, Karbing DS. Determining the appropriate model complexity for patient-specific advice on mechanical ventilation. Biomed Tech (Berl). 2017 Apr 1;62(2):183-198. doi: 10.1515/bmt-2016-0061. — View Citation

Rose L, Schultz MJ, Cardwell CR, Jouvet P, McAuley DF, Blackwood B. Automated versus non-automated weaning for reducing the duration of mechanical ventilation for critically ill adults and children: a cochrane systematic review and meta-analysis. Crit Care. 2015 Feb 24;19:48. doi: 10.1186/s13054-015-0755-6. Review. — View Citation

Smith TC, Marini JJ. Impact of PEEP on lung mechanics and work of breathing in severe airflow obstruction. J Appl Physiol (1985). 1988 Oct;65(4):1488-99. — View Citation

Sulemanji D, Marchese A, Garbarini P, Wysocki M, Kacmarek RM. Adaptive support ventilation: an appropriate mechanical ventilation strategy for acute respiratory distress syndrome? Anesthesiology. 2009 Oct;111(4):863-70. doi: 10.1097/ALN.0b013e3181b55f8f. — View Citation

Thorens JB, Kaelin RM, Jolliet P, Chevrolet JC. Influence of the quality of nursing on the duration of weaning from mechanical ventilation in patients with chronic obstructive pulmonary disease. Crit Care Med. 1995 Nov;23(11):1807-15. — View Citation

* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of mechanical ventilation	Defined as the time from the start of mechanical ventilation, defined as either the time of intubation in the ICU (or the time of admission to the ICU following previous intubation for surgery) and until successful extubation, with successful extubation defined as =48 hours of unassisted spontaneous breathing after extubation.	Until the date of discharge from ICU, up to 12 months.
Secondary	Duration of mechanical ventilation following randomisation	Defined as the time from randomisation and until successful extubation, with successful extubation defined as =48 hours of unassisted spontaneous breathing after extubation.	Until the date of discharge from ICU, up to 12 months.
Secondary	Time from control mode to support mode	Defined as the time following randomisation, from initiation of control modes of ventilation and until initiation of support modes of ventilation.	Until the date of discharge from ICU, up to 12 months.
Secondary	Time from support mode to successful extubation	Defined as the time following randomisation, from initiation of support modes of ventilation and until successful extubation.	Until the date of discharge from ICU, up to 12 months.
Secondary	Number of changes in ventilator settings per day	Defined as the daily registered number of changes to ventilator settings from patient randomization until successful extubation.	Until the date of discharge from ICU, up to 12 months.
Secondary	Time to first spontaneous breathing test (SBT)	Defined as the time from randomization to the first performed SBT.	Until the date of discharge from ICU, up to 12 months.
Secondary	Time to first successful SBT	Defined as the time from randomization to the first successful SBT.	Until the date of discharge from ICU, up to 12 months.
Secondary	Time to first extubation	Defined as the time from randomization to the first extubation attempt.	Until the date of discharge from ICU, up to 12 months.
Secondary	% of time in control mode ventilation	Defined as the time from randomization spent in controlled modes of mechanical ventilation in percent of duration of mechanical ventilation	Until the date of discharge from ICU, up to 12 months.
Secondary	% of time in support mode ventilation	Defined as the time from randomisation which is spent in support modes of mechanical ventilation in percent of duration of mechanical ventilation	Until the date of discharge from ICU, up to 12 months.
Secondary	Time to first period trachemask	Defined as the time of randomisation to the point of trachemask initiation.	Until the date of discharge from ICU, up to 12 months.
Secondary	Use of neuromuscular blockading agents	Defined as the cumulative use of neuromuscular blockading agents from randomization until successful extubation.	Until the date of discharge from ICU, up to 12 months.
Secondary	Use of sedatives	Defined as the cumulative use of sedative drugs from randomization until successful extubation.	Until the date of discharge from ICU, up to 12 months.
Secondary	Number of intubation free days	Defined as the number of days without intubation from randomization until successful extubation.	Until the date of discharge from ICU, up to 12 months.
Secondary	Number of reintubations	Defined as the number of reintubations following extubation from randomization until successful extubation.	Until the date of discharge from ICU, up to 12 months.
Secondary	Number of tracheostomies	Defined as the number of patients having tracheostomy performed from randomization until successful extubation or protocol end.	Until the date of discharge from ICU, up to 12 months.
Secondary	Number of patients on prolonged mechanical ventilation	Defined as the number of patients on mechanical ventilation ongoing for more than 21 days after initial intubation.	Until the date of discharge from ICU, up to 12 months.
Secondary	Number and types of adverse events related to mechanical ventilation	Defined as the incidence of adverse events directly related to mechanical ventilation	Until the date of discharge from ICU, up to 12 months.
Secondary	Frequency of accepting Beacon care system advice	Number of times and the reasons the advice from the Beacon system is overridden and not accepted by a treating clinician.	Until the date of discharge from ICU, up to 12 months.
Secondary	ICU mortality	defined as the mortality from randomization and until death or ICU discharge.	Until the date of discharge from ICU, up to 12 months.
Secondary	Hospital mortality	defined as the mortality from randomization and until death or hospital discharge.	Until the date of discharge from ICU, up to 12 months.
Secondary	Length of ICU stay	defined as the duration of ICU admission from randomization to ICU discharge	Until the date of discharge from ICU, up to 12 months.
Secondary	Length of hospital stay	defined as the duration of hospital admission from randomization to hospital discharge	Until the date of discharge from hospital, up to 12 months.
Secondary	Time to first mobilization	Defined as the time from randomisation until first mobilization, e.g. sitting on the edge of the bed, standing up and marching on the spot	Until the date of discharge from ICU, up to 12 months.
Secondary	Time to independent mobilization	Defined as the time from randomisation until regaining independency, e.g. able to drink/eat or comb hair.	Until the date of discharge from ICU, up to 12 months.
Secondary	Daily patient physiological blood gas status	Defined as daily PaO2/FiO2 from randomization until successful extubation.	Until the date of discharge from ICU, up to 12 months.
Secondary	Changes in Oxygenation Index	defined as daily averages of oxygenation index (Oxygen Index (OI) = (FiO2 x Mean Alveaolr Pressure x 100) / PaO2	Until the date of discharge from ICU, up to 12 months.
Secondary	Changes in anatomical dead space volume	defined as daily changes in dead space volume as continuously measured by the Beacon system.	Until the date of discharge from ICU, up to 12 months.
Secondary	Changes in pulmonary shunt fraction	defined as daily changes in pulmonary shunt fraction as continuously measured by the Beacon system.	Until the date of discharge from ICU, up to 12 months.
Secondary	Changes in end-tidal end-tidal CO2 fraction (FE'CO2)	defined as daily changes in end-tidal CO2 fraction as continuously measured by the Beacon system.	Until the date of discharge from ICU, up to 12 months.
Secondary	Changes in pulmonary mechanics	defined as daily changes in respiratory system compliance as continuously measured by the Beacon system.	Until the date of discharge from ICU, up to 12 months.
Secondary	Changes in metabolism	defined as daily changes in resting energy expenditure as continuously measured by the Beacon system.	Until the date of discharge from ICU, up to 12 months.
Secondary	ICU/hospital lung imaging in relation to prolonged ventilation	e.g. chest CT injury indices.	Until the date of discharge from hospital, up to 12 months.
Secondary	Timed-up-and-go at day 10 (or first mobilisation) and ICU/Hospital Discharge	Timed-up-and-go at day 10 (or first mobilisation) and ICU/Hospital Discharge	Until the date of discharge from hospital, up to 12 months.
Secondary	Sit to stand at day 10 (or first mobilisation) and ICU/Hospital Discharge	Sit to stand at day 10 (or first mobilisation) and ICU/Hospital Discharge	Until the date of discharge from hospital, up to 12 months.
Secondary	Chelsea Critical Care Physiotherapy Assessment score (CPAx) trajectory	Chelsea Critical Care Physiotherapy Assessment score (CPAx) trajectory (performed every 72 hours)	Until the date of discharge from hospital, up to 12 months.
Secondary	Barthel index at hospital discharge	Barthel index at hospital discharge	Until the date of discharge from hospital, up to 12 months.
Secondary	6-minute walk test at hospital discharge	6-minute walk test at hospital discharge	Until the date of discharge from hospital, up to 12 months.
Secondary	3-month +/- 6-month +/- 1-year ICU follow-up lung imaging and function in relation to prolonged ventilation	ICU follow-up lung imaging and function in relation to prolonged ventilation (as per current clinical protocol i.e. if clinically indicated, which may include pulmonary function tests, CT imaging).	Until the date of discharge from hospital, up to 24 months.
Secondary	Sf-36 Health Related Quality of life (patient and carers)	-Sf-36 Health Related Quality of life (patient and carers)	Until one year after hospital discharge, up to 24 months.
Secondary	EQ-5D-5L	EQ-5D-5L	Until one year after hospital discharge, up to 24 months.
Secondary	St George's Respiratory Questionnaire	St George's Respiratory Questionnaire	Until one year after hospital discharge, up to 24 months.
Secondary	mini Mental State examination	mini Mental State examination	Until one year after hospital discharge, up to 24 months.
Secondary	PTSS-14	PTSS-14	Until one year after hospital discharge, up to 24 months.
Secondary	Hospital Anxiety and Depression Scale (HADS)	Hospital Anxiety and Depression Scale (HADS)	Until one year after hospital discharge, up to 24 months.
Secondary	Return to work rates e.g. W&SAS (patient and carers)	Return to work rates e.g. W&SAS (patient and carers)	Until one year after hospital discharge, up to 24 months.
Secondary	Primary and Secondary care utilisation	Primary and Secondary care utilisation	Until one year after hospital discharge, up to 36 months.
Secondary	6-minute walk test	6-minute walk test	Until one year after hospital discharge, up to 24 months.