The health and wellbeing of patients does not depend solely on the quality of health services but also on the condition of the Earth’s ecosystem. Nowadays, anesthesiologists are also challenged to consider ecological and sustainable aspects while promoting the health of their patients such as when deciding on the best way to administer GA.

General anesthesia and the choice of inhalational anesthetics

General anesthesia can either be provided as inhalational anesthesia, balanced anesthesia, or TIVA. While TIVA typically is based on a continuous intravenous application of propofol, inhalational anesthesia is delivered using an inhalational anesthetic for induction as well as for maintenance. Balanced GA is delivered using an intravenous hypnotic for induction, and maintained with a volatile inhalational agent such as sevoflurane, desflurane, isoflurane, or halothane, with or without N2O as a carrier gas.

In a 2012 French study, 72% of anesthesiologists performed GA as a combination of intravenous induction and either desflurane (48%) or sevoflurane (24%). Total intravenous anesthesia was only performed in 17% of the cases. In 8% of cases, the induction technique was not specified, and in 2% of cases, an inhalational induction was performed.23 In contrast, in a 2013 Scandinavian study, only 48.9% of anesthesiologists performed GA maintained with inhalational anesthetics, whereas 51.1% performed TIVA. In 11.9% of these GAs, N2O was used as carrier gas or coanalgesic.24

A 2019 environmental survey by the American Society of Anesthesiologists’ Committee on Equipment and Facilities found that sevoflurane was chosen by 66.4% of participating anesthesiologists (1,215/1,829; 95% confidence interval [CI], 64.2 to 68.6), whereas desflurane was chosen by 22.3% (408/1,829; 95% CI, 20.4 to 24.3).25

Inhalational anesthetics and their characteristics

Isoflurane, sevoflurane, and desflurane are halogenated ethers containing an oxygen atom that connects two fluorinated alkyl groups. Containing chlorine, isoflurane belongs to the chlorofluorocarbons (CFCs).26,27,28,29 These volatile inhalational anesthetics are liquid at room temperature and act through modulation of various membrane-associated proteins. For example, they amplify inhibitory postsynaptic potentials of γ-gamma-aminobutyric acid type A (GABAA) and glycine receptors, and decrease N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-related excitatory postsynaptic potentials.30,31 Furthermore, they bind to nicotinic acetylcholine receptors, blocking the channel pore. By perturbating lipid rafts of cell membranes, they activate phospholipase D2. Consecutive activation of two-pore domain K+ channels causes reversible loss of consciousness.32 Nitrous oxide, in turn, is a colorless nonflammable gas that stimulates cerebral GABA receptors and inhibits spinal NMDA receptors.33

Inhalational anesthetics and their environmental impact

In addition to the clinical and pharmacological properties of inhalational anesthetics, it has become increasingly evident that their environmental toxicity and sustainability characteristics have to be considered as well. In 2014, inhalational anesthetics accounted for worldwide emission of approximately 3 Mt CO2e. Regarding N2O, anthropogenic sources contributed 43% of the total N2O emission of about 7.3 Tg per year, 1–4% of which originated from medical sources.20,34 Currently, inhalational anesthetics are emitted directly and unchanged from anesthesia machine-scavenging systems into the atmosphere. They influence the radiation balance of the Earth’s atmosphere negatively by intensifying IR absorption in the IR atmospheric window, affecting terrestrial regulation of temperature. In fact, they impede heat release back into space not only within but also outside the atmospheric window.6 The extent of this detrimental effect largely depends on molecular weight, specific type of halogen, and its atmospheric lifetime (Table 1).35

Table 1 Environmental characteristics of inhalational anesthetics10,38

As stated above, isoflurane is a CFC. Chlorofluorocarbons as well as N2O (cf. above) contribute to ozone depletion in the stratosphere.10 In contrast, desflurane and sevoflurane have no ozone-depleting effect because of their complete fluorination.36 Nevertheless, comparing the GWP of inhalational anesthetics, desflurane is about 20 times more potent than sevoflurane and five times more potent than isoflurane.

The GWP of inhalational gases is determined by their atmospheric lifetime and their effectiveness at absorbing and emitting IR radiation, called “radiative efficiency.” The high GWP of desflurane is mainly due to its longer atmospheric lifetime of 14 years compared with 3.2 years for isoflurane and 1.1 years for sevoflurane. Additionally, desflurane has the highest radiative efficiency.19 It is important to notice that desflurane has a higher minimum alveolar concentration at 1 atm required to prevent 50% of subjects from moving in response to a noxious stimulus (MAC50) than sevoflurane and isoflurane (6.6 vol% vs 1.8 vol% and 1.2 vol%, respectively).37 Thus, higher concentrations are required to deliver the same clinical effect.38 In 2014, desflurane accounted for 80% of the CO2e emission related to inhalational anesthetics6.

To assess the life-cycle GHG emissions of inhalational anesthetics, it is important to consider the waste anesthetic gas emissions as well as the upstream environmental impact including manufacturing, transportation, packing, and drug delivery.16,39 Desflurane has not only the highest waste anesthetics gas emissions but also the largest nonwaste anesthetics gas emissions. The comparatively high emissions are mainly caused by manufacturing processes and electricity for volatilization during drug delivery.39 As shown by Richter et al., reduced use of desflurane in clinical practice significantly decreases the emission of CO2e due to waste anesthetics gas emissions.40 In contrast, a compensatory increase of isoflurane consumption should be avoided as it contributes to ozone depletion in the stratosphere and, therefore, counterbalances the positive effect.10

Making responsible choices with regard to the use of inhalational anesthetics during GA represents a cost-effective and quickly implementable strategy for reducing the CO2e footprint of anesthesia practice.18

Low-, minimal-, and metabolic flow anesthesia

According to Baum,45 low-, minimal-, and metabolic flow anesthesia is defined by the part of rebreathing and not the absolute level of fresh gas flow (FGF) (Table 241,42,43,44). With decreasing FGF, rebreathing fraction increases (Fig. 1).45,46 The part of rebreathing depends on the oxygen consumption (\(\dot}}_)\) of the patient, FGF, and the volume of the anesthesia workstation’s circle system. Oxygen consumption can either be calculated using Fick’s formula if cardiac output (CO, in L·min-1) and arterial and venous oxygen content are known, or it can be estimated using Brody’s formula.47,48 Accordingly, a healthy 40-yr-old, 80-kg male patient with normal CO consumes about 260 mL oxygen per minute. Contemporary anesthesia machines calculate and display patients’ real-time \(\dot}}_\) based on the partial pressure differences of inspiratory and expiratory oxygen. Therefore, FGF can be decreased to \(\dot}}_\) to reduce waste anesthetic gas to a minimum and to save inhalational anesthetics as well as medical gases.

Table 2 Classification of anesthesia according to fresh gas flow for a 40-yr-old, 80-kg male patientFig. 1

Fraction of rebreathing (in %) depending on fresh gas flow (modified from Baum45 in Hoenemann & Mierke46)

Contemporary anesthesia workstations with target-controlled concentrations of inspired oxygen and expiratory inhalational anesthetic allow for quantitative anesthesia in a closed-circuit system.43 Switching from conventional fresh gas mode to an electronically controlled mode such as “auto control” (Zeus IE®, Drägerwerk AG & Co. KGaA, Lübeck, Germany), “end-tidal control” (Aisys CS2®, General Electric Company, Boston, MA, USA), or “automated gas control” (FLOW-i®, Maquet, Solna, Sweden) is associated with lower consumption of inhalational anesthetics, costs, and GHG emissions.49

In general, anesthesia systems and their components can be safely used with FGFs ≤ 1 L·min-1 under the following conditions: 1) little systemic leakage; 2) mandatory measurement of inspiratory and expiratory concentration of oxygen, carbon dioxide, and inhalational anesthetics; and 3) presence of an integrated carbon dioxide absorber. It is important to prevent accidental dry-out of the carbon dioxide absorber and to use it according to the manufacturers’ instructions and recommendations.50

Intraoperative consumption of inhalational anesthetics

The overall consumption of inhalational anesthetics depends on several factors such as patient age, individual agant MAC50, duration of wash-in and wash-out periods, and time from incision to suture.

Wash-in

After intravenous induction and airway establishment, the inhalational anesthetic is washed in. Kim et al. showed that after application of an iv induction dose of 2 mg·kg-1 of propofol, depth of anesthesia is maintained for approximately nine to 11 minutes for stand-alone administration of propofol.51 Nevertheless, as GA is typically induced combining propofol with an intravenous analgesic drug (e.g., an opioid), the additive effects must be taken into account. The validated noxious stimulation response index (NSRI) can be used to predict the probability of responding to a noxious stimulus considering interactions between hypnotic and opioid.52,53

Prediction tools and previews such as SmartPilot View® (Drägerwerk AG & Co. KGaA, Lübeck, Germany) rely on validated concepts such as MAC or NSRI. They can facilitate anesthesiologic management as they visualize synergistic effects of inhalational anesthetics, intravenous hypnotics, and analgesics.

Clinical experience suggests that for desflurane, an FGF of approximately 0.7 L·min-1 with the vaporizer set to 18%, and for sevoflurane, a FGF of 0.5 L·min-1 with the vaporizer set to 8% appear to be sufficient to maintain adequate depth of anesthesia during the wash-in period. Decreasing FGF during the wash-in period helps prevent unnecessary deep anesthesia and reduces the consumption of inhalational anesthetics. For both inhalational anesthetics, a decrease of FGF from 4 to 1 L·min-1 decreases the consumption of inhalational anesthetic by 45.3% (desflurane) and 51.8% (sevoflurane), respectively. Consecutively, there is also a significant reduction by approximately 45–50% of CO2e emission and costs per minute GA (Table 3).54

Table 3 Consumption, global warming potential, and costs of inhalational anesthetics depending on different fresh gas flows during the wash-in period simulating a male 40-yr-old, 80-kg patient using a Primus IE® (Drägerwerk AG & Co. KgaA, Lübeck, Germany) with a total breathing system volume of 8.0 LSteady state

After initial wash-in of inhalational anesthetic, at a MAC50 of 0.7 to 1.0, a steady state is reached.

Anesthesia with an FGF ≤ 1 L·min-1 does not only effectively maintain intraoperative conditioning (i.e., heating and moisturizing) of inspired gases55 but also saves inhalational anesthetics. The following calculation shows the FGF-dependent consumption of sevoflurane and desflurane during steady state (Table 4). For both inhalational anesthetics, a decrease of FGF from 2 to 0.35 L·min-1 reduces consumption of sevoflurane by 65% and desflurane by 71.4%. This saves approximately 20 EURFootnote 1 and 1.1 kg of CO2e for a two-hour GA.

Table 4 Consumption of inhalational anesthetics during a steady state of 120 min at different fresh gas flows simulating a male 40-yr-old, 80-kg patient using a Primus IE® anesthesia machine (Drägerwerk AG & Co. KgaA, Lübeck, Germany) with a total breathing system volume of 8.0 L

Routinely reducing fresh gas flow saves inhalational anesthetics, reduces CO2e emission, and is cost-effective.

Wash-out

After completion of surgery, the administration of inhalational anesthetics can be terminated. At this point, there is no significant partial pressure difference between alveolar, blood, and cerebral compartments. To enable effective wash-out of inhalational anesthetics, the inspiratory gases must be cleared from inhalational anesthetics by closing the vapor and increasing the FGF to 4–6 L·min-1. During this period, adequate alveolar ventilation must be ensured, and spontaneous breathing efforts of the patient can be supported until the patient fully recovers.

Nitrous oxide as additional anesthetic

Nitrous oxide has been widely used as a carrier gas during balanced anesthesia, and additionally for analgesia during painful procedures (e.g., in children) or during labor, to address treatment-resistant depression, and as a strategy for preventing chronic postsurgical pain in particular populations.39,56,57 Nevertheless, the overall clinical use of N2O has declined.58 Nitrous oxide is emetogenic,59 inhibits the methionine synthase irreversibly by inactivating the enzyme’s vitamin B12 component, and can cause “diffusion hypoxia.”60,61 The ENIGMA-II trial supported the safety of N2O use in major noncardiac surgery,62 but the data remain conflicted.

When N2O is used as carrier gas instead of oxygen, the end-tidal concentration of halogenated inhalational anesthetics can be decreased, reducing the consumption of inhalational anesthetics.39,63 Nevertheless, Baum et al. showed that expenses for the use of N2O—such as technical maintenance for the central gas piping system, antiemetic prophylaxis, and the inhalational anesthetic itself—exceed the additional costs for inhalational anesthetics and intravenous analgesics.60,64 Therefore, the reduced consumption of inhalational anesthetics does not result in net savings. Comparing the total CO2e emission when N2O is used as a carrier gas, there is a net increase for sevoflurane and isoflurane and a decrease for desflurane (Table 5). Nevertheless, this calculation lacks the negative impact of additional N2O to the tropospheric nitrous oxide cycle and the resulting ozone-depleting effect.39,58

Table 5 Ecological impact of inhalation anesthesia with nitrous oxide as carrier gas compared with inhalation anesthesia with only O2 as carrier gas (-N2O)

The renouncement of N2O as a carrier gas allows for safely performing low-, minimal-, and metabolic flow anesthesia. This enables significant savings of inhalational anesthetics and better conditioning of inspired gases compared with high-flow anesthesia, which is required during the wash-in and wash-out periods if N2O is used as a carrier gas. Additionally, the negative impact of N2O on CO2e emissions and ozone depletion can be prevented.

New technologies to absorb inhalational anesthetics

The use of technologies for absorbing inhalational anesthetics from the exhausted air represents a future solution to achieve sustainability and to reduce the ecological footprint of GA.65 So far, several different purification systems received a patent grant such as adsorption by charcoal granules or by molecular sieve as well as destruction using gas-phase photochemistry.66 For example, Doyle et al. showed an effective removal of 1% isoflurane from the exhaled air over a period of eight hours using a silica zeolite hydrophobic molecular sieve adsorbent.67 Alternatively, inhalational anesthetics can be destroyed directly by UV light. The advantage of this system is the lack of additional treatment. Since these technologies are currently only used experimentally, further studies and technological development under consideration of ecological aspects are highly needed.66 It must be stressed that the efficiency of all these technologies is decreased by the use of high FGFs. Thus, minimal or metabolic flow anesthesia is essential to use these technologies beneficially in the future.68

Alternatives to inhalational anesthetics

In addition to the use of technical solutions, the transitions from inhalational anesthesia to alternative techniques such as LRA and TIVA represent another approach to reduce GHG emission.11 Locoregional anesthesia and TIVA can be used equally effectively as inhalational anesthesia if surgery and patient’s condition allows it.

Compared with inhalational anesthesia, TIVA reduces the risk of postoperative nausea and vomiting, pain scores after extubation, and duration of in postoperative anesthesia care unit stay; on the other hand, it prolongs the time to respiratory recovery and tracheal extubation.69 Nevertheless, performing TIVA instead of inhalational anesthesia has environmental costs of its own because of the increased disposable plastic waste, higher propofol consumption, and consecutively increased wastage rate.70,71 Other environmental effects of TIVA are still uncertain.71 Based on the detection of propofol metabolites in the waste water of hospitals, it is important to stress the aquatic toxicity of propofol.70,71,72,73 Propofol is excreted almost entirely in its metabolized, inactive form.74,75 Thus, it can be assumed that the detected propofol metabolites are primarily caused by improper disposal. Therefore, it is important to implement efficient waste disposal systems before converting to TIVA.

Another alternative to TIVA is LRA. A recent Australian study compared the life-cycle GHG emissions for GA with sevoflurane, spinal anesthesia, and the combination of both during total knee arthroplasty. Interestingly, the carbon footprint was similar for all three anesthetic modalities, albeit determined by serval choices. For spinal anesthesia, the emissions were mainly dominated by the electricity consumption for oxygen use and cleaning the reusable equipment. Switching from the Australian grid (mix mainly dominated by fossil energies) to the European grid (with a larger proportion of renewable energies) decreases the carbon footprint of spinal anesthesia by 40%.76 These continental differences stress the importance of defining full life-cycle assessments for different anesthetic approaches in different regions. Future analysis would benefit from datasets for medication synthesis provided by manufacturers.17,