Wintermeeting 2024: Nick Sutcliffe

Why Total Intravenous Anaesthesia (TIVA)

An overview on aspects of patient outcome, oncology, and the environment.
Nick Sutcliffe

Friday 19 January 8:30-9:00


The safety of surgery under anaesthesia has improved markedly over the last century. New drugs and improved equipment have resulted in more accurate dosing and reduced side effects. As mortality has improved, focus has shifted to also include non-lethal postoperative complications such as nausea, vomiting, pain, and cognitive dysfunction. Similarly, it is no longer sufficient to consider only immediate survival after surgery, but also longer-term issues such as cancer recurrence, quality of life and cognitive decline following surgery under anaesthesia.  Propofol based TIVA has several potential advantages over volatile based anaesthesia (VBA), for both the patient and operating room staff, as well as environmental benefits. Evidence is accumulating to support the use of TIVA over VBA, in terms of improved patient outcomes, less toxicity in the local environment and less effect on the global environment relating to greenhouse gas (GHG) emissions.

Patient Outcomes

Surgery is a form of controlled trauma; mortality and complication rates are directly related to the degree of invasiveness of the surgical procedure. This appears to be in part related to the stress response to the injury. This response includes a neuroendocrine/metabolic response mediated by the central nervous system and endocrine system. Also an inflammatory/ immunosuppression response, mediated by factors released from the damaged tissues. Regional anaesthesia can help diminish  the neurologically mediated component but does not abolish it and does nothing to attenuate the inflammatory reaction. The stress response to surgery has been implicated in various states of organ impairment. These include gut, cardiac, renal, and neurological dysfunction in the post operative period. It also suppresses the body’s natural tumour cell suppression and eradication mechanism, which may lead to an increase in cancer recurrence. Various anaesthetic agents interact with these processes in both a beneficial and harmful manner.

Theoretical Drug Effects

Propofol has many theoretical beneficial effects on the stress response to surgery. It has an anti-inflammatory, antioxidant, and anti-apoptosis effect on normal cells, as well as being a free radical scavenger. In addition, propofol does not suppress natural killer (NK) cell or lymphocyte function and increases tumour cell apoptosis. In contrast, volatile agents, although generally anti-inflammatory, suppress NK cell and lymphocyte function and cause apoptosis in clinically relevant doses. Thus, theoretically propofol based TIVA may be superior to volatile anaesthesia, in terms of cancer recurrence and infectious complications.

In addition, propofol has an anti-emetic action, reduces CRMO2 , and cerebral blood flow (CBF). Similarly volatile agents reduce CRMO2, but increase CBF and reduce cerebral auto regulation, as well as increasing post operative nausea and vomiting (PONV).

Volatile anaesthetic agents have a potential advantage in cardiac surgery, due to a cardioprotective effect, mediated by pharmacological pre-conditioning. Propofol has no preconditioning effect. However, opiates appear to offer a similar pharmacological pre-conditioning effect and are often used in conjunction with propofol based TIVA  for cardiac surgery.

Clinical Studies

TIVA has a lower incidence of PONV compared with VBA and this effect is well documented in the literature.
The available evidence tends to support the superiority of propofol in terms of the effect on oncological outcomes, but there is a lack of prospective data to confirm this benefit.  Currently, there are a number of large on-going clinical trails aimed at addressing this issue.
Early studies in cardiac surgery comparing TIVA and VBA, showed a mortality benefit in favour of VBA, thought to be due to the cardioprotective effects of volatile agents. However, more recent studies have failed to show any difference in mortality between the two techniques, which may be explained by the cardioprotective effects of opioids used as part of the TIVA technique. This may also be explained by the beneficial effect of propofol on reperfusion injury and the reduction in the inflammatory effect of cardiopulmonary bypass seen with propofol based TIVA.
Post operative cognitive dysfunction (POCD), is a significant issue in elderly patients and  volatile agents have been implicated as a contributing factor. A Cochrane library review has shown a consistent benefit of TIVA over VBA.

Environmental Issues

Volatile agents have an impact on both the local and global environment. Inhalational anaesthetics are amongst those agents listed under the Control of Substances Hazardous to Health (COSHH) in the UK and the National Institute of Occupational Safety and Health (NIOSH) in the USA. Potential toxic effects, include nausea, dizziness, headaches, fatigue, and irritability. As well as more serious issues such as sterility, miscarriages, birth defects, cancer, liver and kidney disease among operating room staff and their spouses. In the past when there was no real alternative to volatile agents for general anaesthesia, staff in the operating room suite had no option but to accept these potential risks. However,  we now have a viable alternative to VBA, is it therefore acceptable for us to expose front line medical staff to this potential toxicity. We are now also seeing similar pathophysiology in the brain relating to Alzheimer's disease and exposure to volatile anaesthetic agents. At present we lack the data linking the long-term chronic exposure of volatile agents to an increased incidence of Alzheimer's disease in operating room staff, but why take the risk?

The global environmental effect VBA in terms of greenhouse gas (GHG) emissions are well documented. Since there is little metabolism of modern volatile agents, the majority of the administered dose is exhaled by the patient and vented to atmosphere. All volatile anaesthetic agents are potent GHGs with nitrous oxide and desflurane being the worst culprits. The emission equivalence of one hours VBA, ranges from tens to thousands of Kg of CO2, dependent on flow rates, agents used and time horizon. Several countries have taken action to limit the use of nitrous oxide and desflurane or ban them completely, because of these concerns. Even sevoflurane which has less GHG effect than desflurane, if taken in a best-case scenario, produces an order of magnitude more GHG effect than propofol based TIVA.

Barriers to TIVA

TIVA is often perceived as requiring complex equipment and considered as difficult to deliver compared to VBA. However, it is VBA that requires a complex delivery equipment and a scavenging system to deliver safely. Operating rooms usually come preconfigured with the appropriate gas supplies, scavenging and complex anaesthetic workstations with calibrated vaporizers. In contrast, TIVA requires only infusion pumps, a ventilator, and an electricity supply. An operating environment designed only for TIVA would be less complex to design and construct on a new build site, with consequent cost savings. However, anesthetists are difficult to wean off VBA, as it is second nature to them. Many practitioners do not have the knowledge and experience to use TIVA effectively. They consider it a specialised area of practise, not to be undertaken without in-depth knowledge of the pharmacokinetics and pharmacodynamics of intravenous agents.  However, the development of Target Controlled Infusion (TCI) equipment brings an ease of use to TIVA, comparable to that offered by the calibrated vaporizer.

Given the benefits offered by TIVA in relation to patient outcome and the toxicity of VBA in terms of occupational exposure and the global environment, coupled with the ease of use offered by TCI, is now time for a sea-change in anaesthesia?

Yang W., Cai J., Zabkiewicz C., Zhang H., Ruge F., Jiang W.G. The Effects of Anesthetics on Recurrence and Metastasis of Cancer, and Clinical Implications. World J. Oncol. 2017;8:63–70.

Landoni Get al “Volatile Anesthetics versus Total Intravenous Anesthesia for Cardiac Surgery” N Engl J Med 2019; 380:1214-1225.

Wigmore T.J., Mohammed K., Jhanji S. Long-term survival for patients undergoing volatile versus IV anesthesia for cancer surgery: A retrospective analysis. Anesthesiology. 2016;124:69–79.

Miller D, Lewis SR , Pritchard MW, Schofield‐Robinson OJ, Shelton CL, Alderson P, Smith AF. “Intravenous versus inhalational maintenance of anaesthesia for postoperative cognitive outcomes in elderly people undergoing non‐cardiac surgery” Cochrane Database of Systematic Reviews. 21 August 2018

Gaya da Costa M , Kalmar AF, Struys M “Inhaled Anesthetics: Environmental Role, Occupational Risk, and Clinical Use” J Clin Me 2021 Mar 22;10(6):1306.

Sulbaek Andersen MP, Nielsen OJ, Sherman JD. “Assessing the potential climate impact of anaesthetic gases.” Lancet Planet Health. 2023 Jul;7(7):e622-e629.