Circulation physiology and resuscitation
Circulation physiology and resuscitation
Circulation physiology and resuscitation
Specific research programmes
Specific research programmes
The circulation in the cardiovascular system is driven by hydraulic energy supplied in bursts. The effectiveness of the energy production depends on the ventricular-arterial coupling, i.e. the interplay between the contractility and the vascular bed resistance to the blood flow. The total vascular resistance, the vascular impedance, consists of both static and dynamic elements; it depends both upon aortic elasticity and the elasticity of the blood vessels, peripheral resistance in the arterioles and capillaries, the pressure from reflected waves, blood viscosity, and the heart rate. Both vascular impedance and cardiac contractility can change considerably on account of sickness or medication. A disconnect in the interplay between the heart and the vascular bed can dramatically reduce the energy production and the cardiovascular effectiveness.
Today, clinical monitoring of cardiovascular function in critically ill patients is most commonly based on real-time readings of blood pressure and blood flow. Subsequently, only a fraction of all the information found in the continuous, pulsatile curves for blood pressure and blood flow is used. This results in the loss of important information on pulsatility and the peripheral regulation of the circulatory system, which in physiological animal studies has proven significant.
Our research group has in collaboration with the ultrasound group at NTNU developed software for real-time, continuous measurements on blood pressure and ultrasound-measured blood flow. The system, called Ultra-Power (uPWR – Ultrasound-based Cardiac Power), offers several possibilities:
Multiplication of the blood pressure curve with the curve for blood flow from the left ventricle produces an effect curve (Cardiac Power) which describes the amount of hydraulic energy transferred to the circulatory system per unit of time.
Calculation of the share of this energy that is connected to the pulsations in blood pressure and blood flow (Oscillatory Power) is an objective for dynamic ventricular-arterial coupling.
Impedance analyses, which indicate whether changes in impedance has a central or peripheral origin in the circulatory system.
This new tool makes exciting clinical research possible, allows development of new clinical monitoring modalities, and may establish new treatment objectives for critically ill patients. Thus far the Cardiac Power project has resulted in three PhD projects:
Audun Eskeland Rimehaug: “Beat-to-beat cardiac power – minimally invasive assessment of overall cardiovascular performance” (completed, dr. Rimehaug defended his dissertation on December 2, 2016).
Tomas Dybos Tannvik: “Ultrapower, from experimental physiology to patient monitoring. The exploration of a novel Doppler based assessment of human cardiovascular function” (completed, dr. Tannvik defended his dissertation on September 11, 2020).
Hans-Martin Flade: Ultrapower and oscillatory power fraction, new tools for optimizing cardiovascular function in the critically ill patient? (start: Jauary 2021)
There is room, for additional single studies and/or PhD projects.
Cardiovascular dysfunction in sepsis is generally caused by three factors; dilatation of resistance-regulating blood vessels in arteries, increased capillary permeability with leakage of fluid from the blood path, and septic cardiomyopathy with reduced cardiac contractility. In clinical medicine, the circulatory system is often monitored through blood pressure measurements, however, in serious cardiovascular dysfunction, the relation between blood pressure and tissue perfusion is variable and unpredictable. In such situations, blood flow measurements are often used in addition to ensure organ perfusion. However, treatment of cardiovascular dysfunction based on monitoring these values, by use of for example a pulmonary artery catheter, has not proven to affect mortality nor the length of intensive care or hospital stay.
We participate in a large-scale collaborative effort, a project called Sepcease, headed by Professor Hans Torp from the ultrasound group at the Department of Circulation and Medical Imaging, NTNU, with professors Erik Solligård and Jan Kristian Damås of the Mid-Norway Sepsis Research Group. This project intends, in part, to use new ultrasound technology to monitor septic change in peripheral microcirculation; and in part, to use our ultra-power tool (see section on “Ultra Power” for a closer description) to study whether sepsis affects the energy transfer from the heart to the circulatory system. The combination of these two approaches may also offer opportunities to study the relationship between macro- and microcirculation in sepsis.
The Sepcease Project focuses on both the possibility for earlier detection of sepsis, and for improved monitoring of established sepsis. Since sepsis is a heterogeneous condition, we will be looking for patterns that can be used to classify patients, and to adapt treatment to the individual patient. We will also study the effect of the therapeutic interventions to determine whether the new tools can be used to optimize treatment.
Severe kidney failure is often not detected until it has run its course for a while. Animal studies have shown that the kidney failure is preceded by disruption in the renal blood flow autoregulation, which can be detected by simultaneously recording blood pressure and blood flow curves from the renal artery. In these studies, the blood flow has been measured with flow probes placed directly on the renal artery.
To make the method clinically usable, we will conduct non-invasive measurements of the blood flow in renal arteries by use of ultrasound. We do, however, require continuous measurements of flow in the renal artery over the course of several minutes, which is difficult because the subject’s breathing causes the kidneys to move. Therefore, we have sought collaboration with SINTEF’s Medical Technology department, which has developed expertise in imaging organs that move with breathing. St Olavs hospital, NTNU and Medical Imaging and SINTEF have established a joint project called Ultrasound based determination of dynamic autoregulation of kidney blood flow in man (ultra-DARK). The project is funded by grants from the health authorities of Mid-Norway (Helse Midt-Norge Innovasjon and Samarbeidsorganet – Helse Midt-Norfe RHF).
Gerald Dibona, the former head of the American Physiological Society (APS), and Professor Emeritus at the University of Iowa, has performed several of the animal studies that have laid the groundwork for using dynamic autoregulation of renal artery flow for earlier detection of severe kidney failure. He, and Professor Sven Erik Ricksten, Gothenburg, contacted us with a proposal of conducting human studies after learning of our development of equipment for simultaneous measurements of ultrasound-based blood flow and blood pressure. The project was conceived in collaboration with them, and they participate in the projects Scientific advisory Board. Robert Fridthiof, Researcher at Uppsala University Hospital, who has conducted experimental studies on dynamic autoregulation of renal artery flow in sepsis, is also attached to the project.
Every year resuscitation is attempted on approximately 2,500 persons outside hospitals in Norway, and (likely) on approximately 1,500 patients admitted to Norwegian hospitals. When the heart stops completely, it usually occurs either as a result of heart disease (heart attack, for example), or as a result of external factors (drowning, for example). Time is of the essence, and immediate action in the first few minutes (CPR, defibrillation, medication) is of utmost importance for the prognosis. Our research group has – and in close collaboration with medical and technical researchers in Norway and abroad – examined the dynamic development during CPR, the phase that determines whether the patient dies or reestablishes stable circulation.
With modern statistical methods for lifespan analysis, so-called multi-state models, we have described the course of events during CPR (for example the odds that the patient reestablishes stable circulation, or that he/she “loses” circulation after initial resuscitation). Furthermore, we are investigating the factors that influence this course of events (for example the cause of the cardiac arrest), and how the patient’s EKG changes over time.
The work has thus far resulted in several publications, and three PhD projects:
Trond Nordseth: “Clinical state transitions during the provision of advanced life support (ALS) to patients in cardiac arrest” (2014)
Daniel Bergum: “In-hospital cardiac arrest – causes, recognition and survival” (2016)
Gunnar Waage Skjeflo: “PEA development in cardiac arrest (In progress, expected 2019)
We have focused on the occurrence of pulseless electrical activity (PEA) as the first heart rhythm, in particular, since this occurs with many patients, and has not yet been adequately studied; and cardiac arrest in hospitals, since the quick arrival of emergency personnel provides the best opportunities to make observations on the dynamic course of events.
We will be conducting further study analyzing the immediate effect of the medication adrenaline on this course of events, as well as undertaking similar analysis of cardiac arrest and resuscitation in children.
The project aims to develop RescueDoppler - an ultrasound method based on continuous Doppler of blood flow in the carotid artery during cardiac arrest.
Manual pulse palpation is currently the gold standard for detecting the presence or absence of blood flow during cardiac arrest, but it has severe limitations and is neither a rapid nor a reliable method. (Germanoska et al. 2018, Eberle et al. 1996). In a study, 45% of healthcare professionals were unable to accurately detect a central pulse during cardiac arrest. (Moule 2000, Nakagawa et al. 2010).
The absence of a palpable pulse does not necessarily indicate a lack of circulation. If circulation has already been restored, chest compressions are unnecessary and may do more harm than good. Therefore, there is a need for a user-friendly tool to assess blood flow during cardiac arrest.
New ultrasound technology developed by Professor Hans Torp has led to a method for measuring continuous blood flow during resuscitation, called RescueDoppler. The probe is attached to the patient’s neck like a patch and continuously records blood flow, with the potential to improve diagnosis, treatment, and outcomes during cardiac arrest.
Doppler measurements of blood flow of the carotid artery can be performed without interrupting resuscitation, making it an attractive alternative for hemodynamically guided and personalized treatment.
The RescueDoppler system includes a small Doppler probe, an ultrasound scanner and software for signal analysis. The technology is operator-independent and does not require ultrasound expertise.
Automated external defibrillators can diagnose life-threatening cardiac arrhythmias by interpreting the ECG signals, enabling untrained laypeople or bystanders to use them. While defibrillators can detect, treat, and provide feedback on the restoration of normal cardiac rhythm, they lack crucial feedback regarding the successful return of spontaneous circulation (ROSC). Shorter time to ROSC is associated with better long-term survival. RescueDoppler has the potential to provide information about ROSC.
The RescueDoppler project consists of four sub-projects:
- Animal experiments
- Machine learning (artificial intelligence) to define ROSC
- Technical development of the probe, probe system and attachment mechanism.
- Clinical multi-center study
At ANILAB at Nord University in Bodø, animal experiments are conducted on pigs. We have developed a hypotension model and a cardiac arrest model. The hypotension model shows that RescueDoppler correlates well with invasive blood pressure from the carotid artery. In the cardiac arrest model, ventricular fibrillation is induced via an ICD placed in the apex of the right ventricle. Ventricular fibrillation is then defibrillated back to sinus rhythm via the ICD. The purpose of the animal experiment is to determine whether RescueDoppler can provide information about the quality of compressions in addition to ROSC information.
Clinical pilot and multicenter study
The pilot study will be conducted at the prehospital clinic, Nordland Hospital in Bodø, and in-hospital at St. Olav's Hospital, where RescueDoppler will be used in as many cardiac arrests as possible. Afterward, for a period of one year, RescueDoppler will be utilized in as many cardiac arrests as possible at eight different hospitals (St. Olav's Hospital, Akershus University Hospital, Oslo University Hospital Ullevål, Oslo University Hospital Rikshospitalet, Stavanger University Hospital, Nordland Hospital in Bodø, Sahlgrenska University Hospital, Aarhus University Hospital).
RescueDoppler aim to gather information from 320 patients suffering cardiac arrest.
RescueDoppler experimental research group:
Charlotte Ingul (project leader, professor at ISB, NTNU, professor at Nord University), Bjørn Faldaas (Ph.D. student at Nord University), Erik Waage Nielsen (professor at UiT, Nord University), Benjamin Storm (Ph.D. student at Nord University), Eirik Skogvoll (professor at ISB, NTNU), Knut Tore Lappegård (professor at UiT), Gabriel Kiss (associate professor, Department of Computer Science and Informatics), Ole Jacob How (professor at UiT).
RescueDoppler clinical research group:
Charlotte Ingul (project leader, professor at ISB, NTNU, professor at Nord University), Eirik Skogvoll (professor at ISB, NTNU), Hans Torp (professor at ISB, NTNU, UiO), Torbjørn Hergum (PhD, Cimon Medical AS), Guro Mæhlum Krüger (PhD student at ISB), Gabriel Kiss (associate professor, Department of Computer Science and Informatics), Morten Sildnes Andersen (master's student at NTNU), Sunniva Gjerald Birkeli (research nurse at St. Olavs Hospital), Hedda Juni Lund (project coordinator).
- Group of Molecular and Cellular Cardiology (GMCC), NTNU
- Universitetet i Stavanger
- Universitetet i Oslo
- Nord University
- Uppsala Universitet
- Göteborgs Universitet
- Center for Resuscitation Science, University of Pennsylvania
- University of Iowa
- Bioengineering and Resuscitation, University of the Basque Country