Alison Sundset introduces the ODI Medical OXIMONITOR, the first non-invasive medical monitoring system providing accurate prognosis for patients with circulatory failure.
Diseases and conditions where micro-circulatory function is largely impaired represent a major global health problem and a tremendous challenge for both the patient and their relatives. This is a priority for regions such as Europe, where there are millions of people impacted by this condition; for example, 2.7 million acute heart failure (AHF) patients die annually. Microcirculatory failure can often lead to severe complications and death, but there is no current system available to monitor it – but now there may be a way to accurately diagnose circulatory failure.
With the OXIMONITOR system of ODI Medical, we will commercialise a disruptive monitoring technology for which no reliable alternative is currently available, allowing for significant improvement of patient outcomes since healthcare professionals can choose the appropriate treatment that works best for each individual patient under consideration, thus maximising the chances of survival.
Let’s talk about the challenge
Circulatory failure, the inability to deliver sufficient oxygen (O2) to the cells of the body (microcirculation), is a common symptom of many health conditions. When combined, these conditions represent a significant burden for society and health systems worldwide, as can be seen in heart failure (HF) alone, which accounts for 31% of all deaths worldwide (17.5 million people per year). Poor micro-circulation can lead to impaired health, disability and, in severe cases, death.
In the case of patients on cardiac and respiratory support (such as extracorporeal membrane oxygenation (ECMO)), only 17% of them survive, and it can cost up to €1.35m for a one-year course of treatment. Specialists are unable to predict if these patients are clinically dead or if they can recover, because they cannot monitor their microcirculatory function, thus resulting in a misuse of time and resources.
The health status of patients connected to an ECMO machine is currently surveilled using monitors and pulse oximetry to measure heart rate, blood pressure and O2 levels. However, in spite of current technology standards, heart monitors and pulse oximeters encompass big drawbacks:
- Tissue O2 level measurement: Current technologies do not provide vital information about the patient, because they cannot measure O2 delivery to the patient’s cells. So, the medical team are not able to make informed clinical decisions on appropriate interventions and thus have limited ability to reduce the high mortality rate from ECMO patients
- Cost-efficiency: Many national health authorities, e.g. the NHS in the UK, and health insurance companies, e.g. United Healthcare in the US, incur high costs in treating patients on ECMO life support without getting feedback as to the chances of recovery. The average cost for ECMO patients in the NHS is €200,000, while still having nearly a 90% mortality rate during the first year.
So, current techniques cannot be used for predicting outcomes and optimising treatments, as they do not measure how much O2 is available to be delivered to cells from the body (microcirculation). The levels of these monitoring techniques can be within the normal (reference) levels in patients, but who have irreversible circulatory failure.
Thus, the patient may be clinically dead, but the brain is kept oxygenated (through the ECMO machine). In addition, present techniques are ineffective for early detection or deterioration of circulatory failure, so resources are misused on both clinically dead patients and those with a chance of recovering, because physicians cannot correctly track the patient’s progression.
The same applies to other diseases such as severe sepsis, neonatal asphyxia or patients entering into systemic inflammatory response syndrome. There is therefore an urgent need to develop a medical device that can accurately monitor microcirculatory function and provide clinicians with data to enable them to better manage their patients.
What was the solution?
ODI Medical AS is a Norwegian start-up company created in 2014 by Knut Kvernebo, a professor of cardiothoracic surgery, working at the University of Oslo. Kvernebo and his team have spent over 30 years studying microcirculatory function at both a basic and clinical research level. This research has resulted in over 100 scientific peer-reviewed manuscripts published in some of the most prestigious journals worldwide, including Microcirculation, Pediatric Research, Microvascular Research or the Journal of Vascular Surgery. His work has been cited over 1,000 times by other research studies, thus showing the relevance of his work.
The ODI Medical OXIMONITOR was developed by Kvernebo and his team to monitor the microcirculation of the patient in a non-invasive manner and provide clinicians with information to help them guide the treatment of these patients who are at risk of microcirculatory failure.
This technology is based on the proprietary ODI Medical ‘physiological biomarker’ concept, the Oxygen Delivery Index™ (ODIN), which can be used for a wide range of clinical applications such as:
- Monitoring patients on mechanical heart and lung machines
- Evaluation of toxicity of chemotherapy
- Early detection of evolving sepsis
- Monitoring of chronic wounds
- Mass screening of conditions such as Ebola, bird flu or endemic meningitis.
ODIN can be used to make a diagnosis of the function of the circulatory system on an individual patient basis, to provide a prognosis for the specific patient and assess the efficacy of treatment in a specific patient by trend analyses of measurement before and after starting the treatment. Finally, ODI Medical has been able to partner with the world’s leading clinics as voluntary clinical partners to conduct our clinical trials for our first clinical application, ECMO patients.
The OXIMONITOR incorporates two main components. The mLab is a non-invasive point of care (POC) device that uses computer-assisted video microscopy and diffuse reflectance spectroscopy to create an ‘optical fingerprint’ of the patient’s circulatory function.
The non-invasive measurements are performed on the skin at the dorsal side of the hand, making data collection easy in critically sick patients or premature babies.
The OXIMONITOR measures the following parameters:
- Functional capillary density (FCD): Density of active capillaries per mm2. Determined by identifying and counting the capillaries and other morphological objects of interest within one or more region of interest (ROI) of known size. Identification and counting can be computer-assisted. Assessed by video microscopy
- The capillary flow velocity (CFV): Flow velocity of red blood cells (RBC) in individual capillaries. In a state of non-flow or low-flow velocity, when little or no O2 is brought to the tissue. If the velocity is too high, O2 does not have sufficient time to diffuse out from the capillary to the surrounding tissue. Assessed by video microscopy
- Local O2 extraction from the capillaries: Obtained from the arterial O2 saturation minus microvascular O2 saturation (SaO2 – SmvO2). Average total body O2 extraction is ≈ 40-50% before blood returns to the right heart and uploading of more O2 in the lungs. In different tissues, and under stressed disease conditions, a larger part of the O2 can be extracted. SaO2 can be assessed by non-invasive pulse oximetry, while SmvO2 is assessed by spectroscopy
- Morphological structures as ‘haloes’, micro-bleedings, capillary elongation, capillary torquation are identified.
The cLab, based on machine learning technology, collects and analyses the data. The interpretation report and visual display, containing the parameters that form the ODIN, are returned to the clinical site and results made available through a user-friendly dashboard in real time for clinical decision-making and optimising treatment of the individual patient (patient-tailored medicine).
The technological progress and miniaturisation achieved within the field of microvascular imaging during the last several years has allowed ODI Medical to make this technology affordable and amenable for commercialisation within a clinical setting (previously, it was most often used for basic research).
In addition, the machine learning revolution it has arrived and has finally become financially feasible to implement such algorithms into all sort of devices and automate a variety of tasks. Finally, the high prevalence of conditions where microcirculatory function is impaired combined with the lack of reliable techniques available for patient’s microcirculatory monitoring prompted us to develop the OXIMONITOR.
In the proof-of-concept single-centre clinical trial, Kvernebo’s team compared the microcirculation of ECMO patients and healthy controls. This clinical trial compared eight ECMO patients to eight healthy controls using skin microscopy within 24 hours after ECMO.
The ODIN parameters were examined up to three times during their ECMO treatment, or during their follow up. Three patients died on ECMO, five survived. The three dying on ECMO had severely reduced FCD in contrast to survivors, who had FCD values like healthy controls. Capillary flow velocities were expressed as fractions in four velocity categories (0: no flow – 4: brisk flow – too rapid flow). ECMO survivors were like healthy controls.
Patients dying on ECMO has severely reduced capillary flow velocities. Results showed that the surviving ECMO patients had ODIN parameters equal to healthy controls, while the patients dying on ECMO had substantially different ODIN levels than the controls and survivors.
The non-invasive technology has proved to be appropriate in helping manage new-born babies (neonates). In the first neonatal study the ODIN concept was used to assess microcirculation in 25 healthy new-borns on day one, two and three of life.
mLab data was collected during a 20-minute examination, without discomfort for the new-borns and in presence of the parents. The results showed reproducible values of the ODIN parameters through all measurements, and very low inter and intra-observer variability between two independent cLab operators performing the CAVM analyses. No complications were observed.
In another published proof-of-concept study, the ODIN parameters were used to monitor 28 asphyxiated new-borns (critically ill new-borns) on day one, three and four of life, as well as 28 healthy new-borns (controls). The asphyxiated new-borns were treated with mechanical ventilation and lowering of body temperature to 33.5°C for 72 hours, resulting in 20-30% reduction in body metabolic rate (equal to a 20-30% reduction in need of oxygen supply to the cells).
The ODIN parameters clearly showed a marked change in microvascular parameters consistent with the reduction in metabolic rate compared to healthy controls, again demonstrating the clinical power of this technology.
We will initially focus our efforts on ECMO patients with AHF because of the high mortality rates in intensive care units (90% during the first year). Between 2009 and 2014 the use of ECMO worldwide has increased threefold, reaching 6,000 patients in Germany alone in 2014. From 2011 to 2016 there was a linear growth in the use of ECMO across all indications, and an average increase of 16% in the next years is foreseen, leading to more than 108,000 expected ECMO patients in 2020.
ODI Medical recognises that the commercial and clinical opportunity with AHF patients on ECMO is limited in size, but this activity helps show the clinical and economic benefits of the OXIMONITOR. ODI Medical is now expanding its clinical activities with major clinical sites across Europe, USA and Australia to explore how the OXIMONITOR can be used in a variety of other clinical cases to improve patient outcomes cost-effectively.
These clinical uses include:
- Patients with local or systemic circulatory failure: AHF treated with ECMO, left ventricular assist devices or heart transplant, chronic heart failure, sepsis, neonatal asphyxia, patients on chemotherapy or irradiation therapy and patients with eye disease
- Early warning for patients entering into systemic inflammatory response syndrome
- Screening for infectious cases during epidemics such as meningococcal infections and pandemics (e.g. Ebola). In this regard, ODI has several ongoing clinical trials for different applications.
The benefits to society
In summary, the OXIMONITOR represents a medical revolution outperforming the current monitoring technologies in a non-invasive and safe manner for both new-born babies and adults. The benefits of this medical non-invasive technology have led one leading US clinician to speculate that this could be ‘as big as ultrasound’.
ODI Medical is growing the size of the company and resources to enable it to capture all these exciting opportunities and is currently engaged in rounds of funding for these activities.
Please note, this article will appear in issue 9 of Health Europa Quarterly, which will be available to read in April 2019.