Total intravenous anaesthesia in focus

Total intravenous anaesthesia has several advantages over inhalation techniques, and wider adoption will lead to safer, greener, and more personalised anaesthetic care

Modern general anaesthesia is often traced back to Morton’s demonstration of inhaled ether in Boston in 1846. However, total intravenous anaesthesia (TIVA), a technique where anaesthesia is delivered entirely through intravenous drugs rather than inhaled gases, predates this by nearly 200 years. An intravenous injection of opium mixed with alcohol into a dog in Oxford in 1656 resulted in anaesthesia followed by full long-term recovery. Advancements in this field were slow until the development of thiopentone in 1934, which was used to provide a rapid induction and recovery for short surgical procedures, to provide portability, and to avoid explosion hazards with the use of the cautery, which had become an essential new surgical tool. It was also used on prisoners to ascertain the truth about their criminal activities! However, it had an unfavourable pharmacokinetic profile, making it unsuitable for procedures longer than 15 minutes.

In the 1970s, John Glen, a Scottish veterinarian working for Imperial Chemical Industries (ICI), and his team started screening for a medication that possessed the anaesthetic power of thiopentone but allowed rapid recovery. In addition to serving as a new induction agent, such a drug might maintain sedation and thus provide an injected alternative to inhaled anaesthetics. The group also aimed to reduce common unpleasant after-effects of anaesthesia, such as nausea and vomiting.

One of these chemicals, propofol (2, 6-diiso-propylphenol; Diprivan), showed the most
promise, but there were many challenges before they eventually developed a soybean oil-based emulsion formulation. ICI finally approved the drug for commercial development by a majority vote of only one.

In 1986, propofol received a European license. Its pharmacokinetic properties allow for easy titration and rapid recovery. Its market size was over USD $1.04 billion in 2024, as propofol now accounts for 26 per cent of anaesthetics and is in widespread use for procedural and ICU sedation. The most common contemporary drug combination in clinical practice includes propofol for its amnesic effect and remifentanil, an ultra short-acting opioid, for the analgesic component. With strong evidence supporting better postoperative recovery, reduced post-operative nausea and vomiting (PONV), decreased perioperative neurobehavioural disorders (PND), and a lower environmental impact, it is time for TIVA to be adopted more widely.

Like many new techniques, a perceived greater complexity of administration and resistance to change has hindered its advancement. As the drug is now generic, it is one of the cheapest methods of anaesthesia.

The patient – why does propofol- based TIVA make sense?

PONV is one of the leading causes of post-operative discomfort and unplanned hospital admissions, with an incidence of approximately 30 per cent, rising to 80 per cent in individuals with additional risk factors. Inhaled anaesthetics are well-known triggers of nausea and vomiting, while propofol has antiemetic properties. A 2019 Cochrane review indicated a 39 per cent reduction in PONV with TIVA and consensus guidelines recommend it as a technique to lower baseline risk. When surveyed, surgical patients said they would rather endure pain than PONV. As clinicians, we often underestimate the relative importance of this complication.

TIVA also facilitates a smooth recovery, and patients report feeling less groggy after inhaled anaesthesia. This is particularly advantageous in day-case surgeries, where rapid recovery is crucial for timely discharge.

TIVA may also provide neuroprotective benefits. PND includes postoperative cognitive dysfunction (POCD), postoperative delirium (POD), and emergence delirium (ED). A recent systematic review found a statistically-significant decrease in POCD and POD with TIVA.

ED is significantly less common after propofol anaesthesia, especially in children. This might be attributed to its impact on cerebral metabolism, as sevoflurane has been found to elevate cerebral lactate and glucose levels, which are associated with a higher incidence of ED. Furthermore, the increased cortical activity induced by sevoflurane during the unconscious state may disrupt the brain’s ability to restore coherent connectivity upon waking.

Propofol reduces morphine consumption and pain scores 24 hours after surgery. It also acts on other receptors involved in pain signalling, decreasing the incidence of chronic post-surgical pain. Although a statistically-significant reduction in pain scores was observed through plausible mechanisms (such as antioxidant and anti-inflammatory effects), the clinical relevance remains unclear.

Some patients, although rare, require a TIVA anaesthetic because of malignant hyperthermia, a life-threatening genetic condition that can be triggered by inhalational anaesthetic agents, which may also precipitate rhabdomyolysis in susceptible patients.

There is a growing interest in cancer recurrence post-surgery. Vitamin E analogues have also been proposed to lower the risk of cancer. The structure of propofol is similar to that of these analogues. The stress response from surgery leads to immunosuppression, and propofol preserves the immune system, along with antioxidant and anti-inflammatory effects. Propofol may benefit patients undergoing cancer surgery by facilitating a more rapid return to intended oncological treatment, a critical treatment metric. While definitive evidence is pending, positive signals in the literature are emerging.

The surgery – why does TIVA make sense?

Beyond enhancing individual outcomes, TIVA also has broader implications for healthcare efficiency and system-wide resource utilisation. It reduces patients’ time to be ready for discharge after day-case surgeries. Faster recoveries and fewer unplanned admissions improve patient flow, keep operating lists on schedule, and shorten hospital stays.

For certain surgical specialities, the benefits of TIVA extend beyond recovery. Propofol maintains flow-metabolism coupling and has neuroprotective effects. Additionally, TIVA has a lesser impact on intraoperative nerve monitoring, which is essential for the safe conduct of specific neurosurgical and spinal procedures.

TIVA, which separates anaesthesia from ventilation, benefits patients undergoing airway procedures. This technique contributes to improved surgical field visualisation, decreased blood loss, and reduced operating time, all of which have led our surgical colleagues to request it. Inhalational anaesthetic agents may induce coughing, apnoea, and laryngospasm, but these reactions are less likely to occur with TIVA.

The environment – why does TIVA make sense?

A more recent factor in adopting TIVA is the environmental advantage of a reduced carbon footprint.

Desflurane, isoflurane, sevoflurane, and nitrous oxide are potent greenhouse gases (GHG). Anaesthetic gases enable the atmosphere to store more energy from the sun than CO². Desflurane, in particular, has a global warming potential 2,540 times greater than CO² over 100 years. In the UK, inhalational anaesthetics have been shown to contribute up to 5 per cent of the total carbon footprint of healthcare.

Hospitals that use only TIVA emit 20 times less GHG per case than those relying on inhalational agents. There is no direct emission of GHG during TIVA anaesthesia, but the combustion of plastic consumables produces carbon dioxide. The standard set-up totals approximately 270g of plastics, which, when combusted, produces 1.4kg of carbon dioxide. Many healthcare institutions have actively worked towards phasing-out desflurane and nitrous oxide, with estimates suggesting this could be equivalent to taking tens of thousands of cars off the roads. Desflurane anaesthesia has virtually stopped in Sweden and parts of Canada, significantly reducing carbon emissions. Although no anaesthetic technique is carbon-neutral, TIVA is the most sustainable option available and will remain so until more effective waste gas capture technologies are developed.

The use of TIVA also provides occupational health benefits by preventing staff exposure to anaesthetic gases, which can be dangerous with prolonged exposure. By reducing waste anaesthetic gas emissions, TIVA is the preferred choice for institutions implementing green initiatives. Trace anaesthetic gases have been associated with headaches, fatigue, and potential reproductive risks for theatre staff.

The Green Committee was established at our base institution, Tallaght University Hospital, in 2019. It employs a multifaceted approach to reducing the hospital’s overall carbon footprint. The perioperative division aims to phase out the nitrous oxide pipeline, update and expand our TIVA pumps, and minimise theatre waste by enhancing recycling.

Barriers to widespread adoption

Despite its growing popularity, several barriers limit TIVA’s widespread adoption. While some concerns are outdated, others stem from practical challenges related to training, equipment availability, and implementation across various healthcare settings.

Training and familiarity

A significant challenge to TIVA adoption is training. Most anaesthetists initially learn inhalation anaesthesia, where the levels of anaesthetic gas are easily measured through end-tidal concentrations. TIVA requires a different skill set, including an understanding of pharmacokinetics, drug titration, and EEG-based monitoring to prevent under-dosing and accidental awareness.

Although pharmacokinetic target-controlled infusion (TCI) systems have made TIVA administration as easy as using a vaporiser and guidelines recommend standardised training, implementation remains inconsistent. Many hospitals and clinicians default to inhalational anaesthesia due to familiarity rather than clinical superiority.

Equipment issues

Although research and development in this area are rapidly advancing, no widespread technology is available to alert anaesthesiologists about disconnection or measure real-time propofol concentration. This may explain our enthusiasm for positioning the patient with an arm visible during an operation. New technology demonstrates agreement between plasma and exhaled propofol concentrations, indicating that proton transfer mass spectrometry can be utilised for real-time propofol monitoring. Equipment availability continues to pose a challenge. TCI pumps are preferred for TIVA compared to manual infusions, which are not widely accessible, especially in low-resource settings.

Cost misconceptions

TIVA has long been viewed as more expensive, a belief originating from a time when proprietary infusion pumps and drug costs were high. However, a cost comparison demonstrated that TIVA is significantly less costly than sevoflurane when factoring in consumables, drug wastage, and anaesthetic duration, and five to 10 times cheaper than desflurane, depending on flow rates.

Although the initial set-up costs of a TIVA system – such as infusion pumps and processed EEG monitors – are high, studies indicate that these costs are offset by reduced use of antiemetics, shorter hospital stays, and lower anaesthetic gas consumption. Some research suggests that institutions primarily using TIVA have lower costs per case.

Accidental awareness under TIVA

Concerns about accidental awareness during TIVA primarily arise from the UK and Ireland 5th National Audit Project (NAP5) of the Royal College of Anaesthetists and the Association of Anaesthetists of Great Britain and Ireland (AAGBI) into accidental awareness during general anaesthesia. The project aimed to examine, report on, and promote improvements in practice by focusing on significant patient-specific events. Accidental awareness was reported as twice as likely with TIVA as inhalational anaesthesia; however, this assertion is misleading. Three-quarters of these cases were preventable and related to non-TCI techniques (manual infusions, fixed-rate dosing, intermittent boluses), all of which are less precise and more prone to errors. Notably, the incidence of awareness was extremely low.

High-risk situations, such as mid-case conversion from inhalational anaesthesia, patient transfers (particularly the use of anaesthetic induction rooms), and remote settings without adequate monitoring, further contribute to awareness. The AAGBI Safe Practice of TIVA guidelines highlight that the risk of awareness is minimal when TCI is used correctly alongside EEG-based monitoring. Some medications we use as adjuncts to TIVA can make the processed electroencephalogram readings unreliable.

That said, with proper training in reading waveforms and adherence to best practices, TIVA is no more likely to cause awareness than inhalational anaesthesia.

Haemodynamic instability

Failure to tailor TIVA to specific patient requirements can lead to adverse events. In 49 out of 811 reported cases of perioperative cardiac arrest in NAP7, TIVA and/or remifentanil were mentioned in the comments. Significantly, the pre-arrest care was rated ‘poor’ in most instances, a lower care rating than in the overall dataset. Lower doses, slower induction, vasopressors, and sometimes different drug choices may have prevented these events. Adverse outcomes were more common in older, unwell, or frail patients undergoing emergency surgery. This highlights that TIVA may be a relatively advanced technique in specific cohorts and should be reserved for anaesthetists with sufficient experience.

Benefits of inhalational anaesthetics

There may be benefits in some scenarios, but these are often overstated. The cardioprotective properties of inhalational anaesthetics have been demonstrated experimentally and in haemodynamically-stable patients undergoing coronary artery bypass graft. Both sevoflurane and propofol exhibit cardioprotective properties, although in different ways. Sevoflurane may exert its effects through pharmacologic preconditioning, and this benefit is mitigated in patients who already have myocardial ischaemia-induced preconditioning, while propofol protects via antioxidant effects. Propofol during bypass is associated with lower levels of cytokines and inflammatory biomarkers up to 24 hours post-surgery.

No IV access is required for gas induction, which can be useful in certain patient cohorts. Additionally, sevoflurane is a potent bronchodilator and has analgesic properties. Less drug interaction occurs, since the majority is exhaled unmetabolised.

Conclusion

Anaesthesia is shifting towards a more eco-conscious and patient-centred approach. It should mitigate the stress response to surgery, improve surgical conditions, and enhance recovery, all while streamlining hospital workflows and lowering environmental impact. As smart pumps refine delivery and new drugs enhance safety, inhalational agents may become the exception rather than the norm.

While this transition from anaesthetic gases is voluntary, who knows what the future holds? The Montreal Protocol, established in 1987, aims to reduce the consumption of substances that deplete the ozone layer. The Kigali Agreement, a recent amendment, focuses on decreasing the use of hydrofluorocarbons (HFCs) by 85 per cent. Anaesthetic gases, which are HFCs, are not currently prohibited due to their medical necessity.

The challenge is to close training gaps, improve accessibility, and standardise best practices. By embracing TIVA, we move toward a future of safer, greener, and more personalised anaesthetic care.

It is vital to remember that all modern anaesthetics are safe, and the best anaesthetic for your patient will always be the decision of the responsible anaesthesiologist.

References on request
Email: claire.nestor@tuh.ie