iTrend project extension and review of progress – Part 1 early developments -Phase 1 2017-2019

The iTrend Intelligent Technologies for Renal Technologies programme kicked off in March 2017 as a collaboration between Derby University, Nottingham University and Royal Derby Hospital. The aim of the programme is to improve outcomes for renal dialysis patients by delivering personalised treatment regimes, in particularly, predicting the onset of hypotension and modulating or modifying treatment. So far the team has developed hardware and software for non-invasive continuous monitoring of blood pressure, without compromising patient experience. In parallel to the main iTrend project, the team secured a Kidney Research UK Stoneygate Award (2021-2023) – DIAMONDS Dialysis Monitoring for Decision Support, to develop real-time blood pressure prediction during dialysis treatment. The iTrend project is now extended until 2023 to investigate the effectiveness of treatment modulation techniques in controlling and mitigating the onset of hypotension during treatment. By mid 2023, the programmes will have collected continuous blood pressure and other physiological data from over 200 patients In the Derby Royal Hospital (RDH) Renal Unit, during multiple 4-hour treament sessions for each patient in order to support the development of the programme

Project Inception

In 2015, Derby businessman Mel Morris introduced me to Profs Maarten Taal and Nick Selby from Nottingham University, and both Consultants in the Renal Unit at RDH. with the aim of brainstorming potential collaborative research programmes. We identified reduced perfusion caused by hypotension during dialysis treatment as a major problem to be addressed, and subsequently that real-time non-invasive continuous blood pressure monitoring, BP prediction and treatment modulation  would be the key developments of any programme. Mel, via the MStart Trust, funded the initial iTrend Phase 1 project which ran March 2017 to March 2020.

iTrend was augmented by (now Dr.) Carol Stalker’s PhD studentship supervised by University of Derby Vice Chancellor Kath Mitchell, Prof James Alander and myself, focusing on the impact of acceptance on patient outcomes.

• Stalker, C., Elander, J., Mitchell, K., Taal, M.W., Selby, N. & Stewart, P. (2018). What is acceptance, and how could it affect health outcomes for people receiving renal dialysis?; Health Psychology Update, 27 (2), 17-23.

Modeling of the cardiovascular system and associated dialysis machine interactions required the construction of ‘Steve’ our cardiovascular lab simulator. RDH Renal Unit donated a fully functioning dialysis machine to our lab brought over and installed by Andy Muggleton, who has contributed substantial practical experience to this programme.

Steve is fully instrumented and under computer control, comprising

• pulastile heart pump with controllable heart rate, systolic/diastolic phase and stroke volume
• variable arterial wall compliance
• variable peripheral resistance
• brachial artery and ‘arm’ with arterial send, venous return and a synthetic fistula
• connected to dialysis machine via standard needles and lines
• multiple flow, pressure sensors across the entire system
• entire control and data acquisition system operated under Matlab/Simulink via National Instruments DAQ devices

The vascular system simulator ‘Steve’ was designed by Prof Jill Stewart and built by me in the lab. It allowed the safe and robust development of the subsequent continuous blood pressure monitoring equipment in a safe environment. Interestingly, its performance and operating characteristics were so close to the human version that the BP estimation software developed on the simulator needed relatively little further development when used on the Renal Unit. This was very much down to Prof Jill’s experience in fluid dynamics delivering a great design. It’s worth noting that this ‘analogue twin’ completely outperforms any comparable digital twin both in terms of development time and expected accuracy.

Phase 1 Patient Study

Around this time, I worked with Dr Latha Gullapudi and Dr Bethany Lucas to perform the Phase 1 patient study which was centered around capturing complete 4-hour physiological monitoring data from patients during dialysis treatment. 50 patients were monitored on three separate treatment sessions each via a Finapres Nova machine. this highlighted the difficulties of obtaining high quality data over a 4 hour period from patients who aren’t still, and often exhibit compromised cardiovascular performance. Additionally over this period of time, wearing inflating and deflating finger cuffs often leads to degradation of measurement performance, finger discomfort and reduced levels of patient experience. Nonetheless. 150 patient studies were completed, leading to novel analysis of both pulse and blood pressure variations during dialysis:

• Venkata R Latha Gullapudi, Kelly White, Jill Stewart, Paul Stewart, Mohamed T. Eldehni, Maarten W Taal, Nicholas M Selby, ‘An analysis of frequency of continuous blood pressure variation and haemodynamic responses during haemodialysis’, Journal of Blood Purification, July 2022; 1-15. Doi:10.1159/000516935
• Stewart Jill, Stewart Paul, Walker Tom, Gullapudi Latha, Eldehni Mohamed T., Selby Nicholas M., Taal, Maarten W. (2020), ‘Application of the Lomb-Scargle Periodogram to Investigate Heart Rate Variability during Haemodialysis’, DOI:https://doi.org/10.1155/2020/8862074, Journal of Healthcare Engineering, Volume 2020, Article ID 8862074, 18 pages, 2020/12/08

At the end of this period, technology was designed and built to be deployed in a new patient study to verify the potential for continuously estimating BP from dialysis line pressures. The project delivered a significant number of conference outputs during this phase.

• Gullapudi, J. Stewart, P. Stewart, T. Walker, K. White, TE Eldehni, MW.Taal, NM. Selby, ‘Frequency analysis reveals unique haemodynamic responses to haemodialysis: Baseline results from the iTREND study’, European Renal Association – European Dialysis And Transplant Association Annual Congress, Budapest, Hungary, 13-16 June 2019
• Gullapudi, J. Stewart, P. Stewart, T. Walker, K. White, TE Eldehni, MW.Taal, NM. Selby, Development of an in-vitro simulation model to investigate hemodynamic responses during hemodialysis’, European Renal Association – European Dialysis And Transplant Association Annual Congress, Budapest, Hungary, 13-16 June 2019
• Gullapudi, J. Stewart, P. Stewart, T. Walker, K. White, TE Eldehni, MW.Taal, NM. Selby, ‘Measuring pressure waves in dialysis lines to derive continuous arterial blood pressure: pilot work in an in-vitro and in-silico model’, European Renal Association – European Dialysis And Transplant Association Annual Congress, Budapest, Hungary, 13-16 June 2019
• Stalker, K. Mitchell, J. Elander, P. Stewart, M. Taal, N. Selby, ‘The impact of acceptance of illness on quality of life outcomes for haemodialysis patients’, UK Kidney Week 2019, 3-5 June, Hilton Brighton Metropole.
• Gullapudi, J. Stewart, P. Stewart, T. Walker, K. White, TE Eldehni, MW.Taal, NM. Selby, ‘Frequency analysis reveals unique haemodynamic responses to haemodialysis: Baseline results from the iTREND study’, UK Kidney Week 2019, 3-5 June, Hilton Brighton Metropole.
• Gullapudi, J. Stewart, P. Stewart, T. Walker, K. White, TE Eldehni, MW.Taal, NM. Selby, Development of an in-vitro simulation model to investigate hemodynamic responses during hemodialysis’, UK Kidney Week 2019, 3-5 June, Hilton Brighton Metropole.
• Gullapudi, J. Stewart, P. Stewart, T. Walker, K. White, TE Eldehni, MW.Taal, NM. Selby, ‘Measuring pressure waves in dialysis lines to derive continuous arterial blood pressure: pilot work in an in-vitro and in-silico model’, UK Kidney Week 2019, 3-5 June, Hilton Brighton Metropole.
• Carol Stalker, James Elander, Kathryn Mitchell, Paul Stewart, Maarten Taal, Nicholas Selby, ‘What aspects of acceptance influence health related quality of life in Haemodialysis patients?’, Division of Health Psychology Annual Conference 2019, 10-11 July, Renaissance Manchester City Centre Hotel
• Carol Stalker, James Elander, Kathryn Mitchell, Paul Stewart, Maarten Taal, Nicholas Selby, ‘What aspects of acceptance influence health related quality of life in Haemodialysis patients?’ British Psychological Society, Division of Health Psychology conference, Manchester UK, 10th – 11th July, 2019.
• Gullapudi, J. Stewart, K. White, TE Eldehni, P. Stewart, T. Walker, MW.Taal, NM. Selby, ‘Characterisation of haemodynamic responses to haemodiaysis using frequency analysis if continuous blood pressure measurements’ American Society of Nephrology, Kidney Week 2019 Conference, 7-10 November 2019, Washington Convention Centre, Washington DC, USA.