Intensive care medicine in 2050: the ICU in vivo
KeywordsIntensive Care Unit Synthetic Biology Personalized Medicine Intensive Care Medicine Extracorporeal Membrane Oxygenation
The specification for the real-time acquisition of essential physiological variables is dictated by the Shannon–Nyquist sampling theorem where sampling must occur at least at twice the rate of the fastest changing control variable . This requirement is currently not met in the monitoring of several organ systems (e.g., kidney) because of intermittent sampling of essential variables (e.g., biomarkers). Achieving optimal measurement of such variables will require targeting biosensors to defined locations throughout the patient . The parameters and location of these biosensors will be dictated by pathophysiology research leading the way for technology development for the ICU of 2050. The sensing of a physical variable or chemical substance in vivo requires biorecognition, signal transduction, and a detector. Sensors would be monitoring hemodynamic variables related to oxygen transport and utilization, the presence of biomolecules, parenchymal cell function, or gene transcription factors in various physiological compartments of the body. Even currently, biosensors are being manufactured at the submicron level (e.g., [9, 10]) and it is expected that such nanodevices will be standard point-of-care in the ICU of the near future. Specialized novel materials are being developed including innovative synthetic materials such as nanocarbon tubes and synthetic biology in which biomolecules from biology such as antibodies and chemical and electrical sensors are incorporated into solid-state components [9, 10]. The introduction of mobility to biosensors or theragnostic drug delivery devices by use of micro- and even nanomotors can allow homing of these sensors to target locations in the patient . Sensors could also consist of swimming imaging capsules or implantable biosensors as part of organ assist devices to provide closed loop control or non-invasive externally located sensors that communicate with in vivo sensors. Equally important in achieving the aims of the future ICU in vivo will be the development of telecommunication technology for the transmission of information between biosensors and outside the patient to a remote station. Telemetry could transmit images from in vivo microdevices, allowing visualization of the functional condition of internal organs.
What will be new in 2050 is that all essential physiological variables will be monitored throughout the patient continuously in time, thereby mapping integrally the temporal and spatial (patho)physiological status of the patient. Concepts such as feedback and set point will be developed to take the complexity of the critically ill patient into account and be multivariate and changing in time. In addition biosensors will be optimized in number, parameters, and location to provide essential information to drive therapeutic theragnostic  modalities normalization or organ function and outcome. Such information will also control and support implantable artificial organs and organ assist devices. Currently placed ex vivo devices such as continuous venovenous hemofiltration, extracorporeal membrane oxygenation, and mechanical ventilation will be placed in vivo and form part of the physiology of the patient in the ICU of 2050 . The sensors of the ICU in vivo will generate massive amounts of information which will be fed into a time variant self-learning physiological model of the patient [14, 15]. Such a “virtual patient” which will form the ex vivo platform for the control of the patient by the intensivist (Fig. 1).
There will be those that may remember the 1966 cult film The Fantastic Voyage, in which Stephen Boyd, Raquel Welch, and Donald Pleasence play medical doctors of the future and treat an incurable critically ill patient by entering a submarine that becomes miniaturized and injected into the circulation of the patient. Although the miniaturization of intensivists is not envisaged in the foreseeable future, many if not most of the elements of the ICU that are currently placed outside of the patients will, in my view, be administered in vivo. In this context a better paradigm for predicting the future ICU of 2050 than the saying of Niels Bohr quoted at the beginning of this paper would be that of Alan Kay who said that “the best way to predict the future is to invent it.” It will be up to the intensivists, the scientific community, and ultimately to industry about whether the ICU in vivo will indeed be a reality. Only the future will tell.
The author wishes to thank Yasin Ince for making Fig. 1.
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Conflicts of interest
Dr. Ince runs an Internet site microcirculationacademy.org which offers services (e.g., training, courses, analysis) related to clinical microcirculation.
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