Fresenius Kabi - A dose of simplicity

Target-controlled infusion systems can improve the safety and clinical outcomes of patients undergoing general anaesthesia, as Dr Francisco A Lobo and Dr Alexandra Saraiva from the Anaesthesiology Department of the Centro Hospitalar do Porto explain.


During the past three decades, anaesthesiology has contributed significantly to the improvement of the safety of patients undergoing surgery. Anaesthesia-related mortality rates in the US have decreased to just one death for every 300,000 people administered anaesthetic.

New drugs with favourable pharmacokinetic and pharmacodynamic profiles, new monitoring strategies and devices, implementation and development of checklists, and continuous medical education programmes are some of the reasons for the maintenance of anaesthesia as a safe and high-quality medical activity.

Nevertheless, frontiers beyond short-term outcomes have recently started to be considered. Mounting evidence shows that inhalational anaesthetic agents promote neuronal cell death in the brains of infantile rodents and non-human primates, leading to permanent neurocognitive dysfunction, while the same agents promote hallmarks similar to that of Alzheimer's disease. Anaesthesiology and public health authorities are highly concerned as to whether the same effects may also occur in humans, particularly with regards to patients that are either very old or very young.

On the other hand, environmental concerns regarding the impact on the global climate of the potent inhaled anaesthetic agents in use worldwide are growing.

Sceptics declare that these are simply roads that lead nowhere, while others believe that serious, multidisciplinary research should be promoted to shed light on the subject.

Strike a balance: tailored anaesthesia

In modern clinical practice, the ideal anaesthetic is classically represented as a triangle, hypnosis or unconsciousness, analgaesia, and areflexia and immobility at the three corners. To attain these effects, several drugs may be used simultaneously. When this is achieved using a combination of intravenous and inhaled anaesthetics, it is known as 'balanced anaesthesia'.

Total intravenous anaesthesia (TIVA) is a technique involving the induction and maintenance of general anaesthesia with intravenous drugs alone, and differs from balanced anaesthesia in that volatile agents and nitrous oxide are avoided.

The choice of a particular anaesthetic technique is a decision made by the anaesthesiologist, taking into account the type of surgery and the condition of the patient, as well as the needs and preferences of the patient and surgeon, and their own personal preferences. For decades, anaesthetic drug dosing was based on average populational references, with indirect surrogate clinical end points as haemodynamic parameters used to guide and titrate the doses administered.

For intravenous anaesthetic drugs, such as opioid drugs or the hypnotic propofol, new means of delivery have been developed that use pharmacokinetic models incorporated into computerised pumps. These continuously calculate the concentration of the drug in different compartments using individual covariates such as the weight, gender or age of the patient, and take into account the distribution and elimination of the drug.

In this way, these target-controlled infusion (TCI) systems allow rapid establishment of a stable blood concentration of the drug, which the anaesthesiologist can easily assess via the effect on different clinical measures.

Measuring the effect of anaesthetic drugs within the central nervous system has previously been difficult.

On first sight, the analysis of the electroencephalogram (EEG) seems to be a reasonable way to see what is going on in the anaesthetised brain, but its complexity and high variability, its cortical origin and the different effects caused by different drugs require attention and skills not necessarily possessed by the anaesthesiologist.

Some monitoring systems that process and quantify the EEG signal have been developed to help the anaesthesiologist to titrate and adjust the individual needs during surgical procedures, avoiding underdosing and the possibility of occurrence of awareness or overdosing with prolonged recovery times and higher incidence of side effects.

Other parameters were also described and launched into the market, aiming to measure the nociception/antinociception balance during anaesthesia by pupil diameter, the EEG or the plethysmography variability.

The future is now

There is mounting evidence showing that intravenous anaesthesia, nowadays based on propofol and remifentanil infusions, offers various advantages over traditional inhalational anaesthesia.

While pharmacokinetic models were developed to calculate and show the concentrations after a drug dose, the TCI systems work in reverse, using real-time pharmacokinetic models to calculate the rate of distribution and metabolism, and hence the drug dose, using individual covariates.

Modern general anaesthesia and sedation practice should prioritise the use of safe IV drugs with favourable profiles that do not interfere with the normal neurodevelopmental or aging processes and deliver them to individual patients using smart systems such as TCI pumps, with optimised, easy-to-interpret surrogate clinical end points.

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