# Model Predictive Control and Its Role in Biomedical Therapeutic Automation: A Brief Review
## 3 MPC in Biomedical Applications
### Anaesthesia  
Anaesthesia is widely employed in various applications, particularly in the medical field, including in operations requiring incisions, dental surgeries and intensive care. The fundamental goal of anaesthesia is to provide a painless experience to a patient undergoing surgery by putting him or her into an unconscious condition. The entire functional scenario of anaesthesia can be divided into three temporal phases: induction, maintenance and emergence. The opioid drug propofol is commonly used in conjunction with other fast-acting opioids during the induction of general anaesthesia. An under-dosageof anaesthetic medicines might result in the patient being aware of the operating situation or insufficient analgesia administration. On the other hand, a patient receiving more medication than necessary can also face detrimental effects. Therefore, the major concern in anaesthesia administration is to maintain the optimum level of sedation during and after induction, which is one of the most difficult tasks in the medical field. Complications may arise following surgery as a result of post-operative pain medication or due to the administration of insufficient intra-operative anaesthetics. Considering the large number of individuals who undergo surgeries every day around the globe, automated regulation of total intravenous anaesthesia (TIVA) is of paramount importance. A higher clinical workload, the wide variety of anaesthesia infusion practices to cater to large inter-patient variability (correlated with doctors' expertise) and the repeated use of a constant drug infusion rate (slightly over-dosing) are pertinent issues that need to be addressed. Recently, the pandemic outbreak of COVID-19 brought to light specific dangers such as acute cardiac damage and arrhythmia associated with infected patients that required special attention during anaesthesia [80]. The solution to the difficulties associated with anaesthesia is three-pronged: (i) robustness to disturbances (such as noise in the measured variables and nonreceptive stimuli); (ii) preventing overdosage by the minimization of the control effort; and (iii) dosage management to control pharmacokinetic and pharmacodynamic drug interactions. MPC is a proven methodology that can be used to deliver such multifaceted solution approaches. A wide range of hypnotic and analgesic medications, such as propofol and remifentanil, are suitable anaesthetic actuators. These medications can be delivered through computer-controlled automated perfusion syringes, which are suitable for intravenous anaesthesia and pain relief. There are several indicators available to measure the depth of anaesthesia, including the BIS index, EEG signal entropy measures, and auditory evoked potentials [81]. In [81], researchers designed a control loop based on an in situ model and used it for the delivery of an opioid analgesic (remifentanil) and an anaesthetic (propofol). The authors simulated the patients' bio-responses (in situ), such as heart rate, arterial pressure and bispectral index, using a pharmacokinetic-dynamic model. This methodology allowed for predicting the bio-responses of the patients as would occur in a real-life scenario. The authors' simulation of the induction phase of anaesthesia was successful in terms of obtaining a rapid and risk-free response from the patient. This was accomplished by designating the arterial pressure and the bispectral index as controlled variables, as well as by imposing appropriate bounds on the plasma concentration and the controlled variables. Overdosing and underdosing are both potentially dangerous outcomes during intravenous anaesthesia, so it is important to find the right pace of delivering anaesthetic medicines to the patients. The connection between the dose of anaesthetic given to a patient and the hypnotic effects it has on that patient has been studied by researchers using a pharmacokinetic-pharmacodynamic (PK/PD) model built specifically for this purpose [82].