Global Warming Impact of Nitrous Oxide

Environmental hazards of human activity are a topic of present day world, global warming being one of the leading concerns. Gases that contribute to this are greenhouse gases. Nitrous oxide (N2O) is a greenhouse gas that is commonly used in medical practice, mostly confined to provision of anaesthesia during surgical procedures in the operation theatre. N2O is not a potent anesthetic, and is used as a carrier for volatile anesthetic during general anaesthesia. This is to reduce the use of volatile anesthetics and other analgesic drugs while maintaining adequate depth of anaesthesia and analgesia. The N2O gas that is used during general anaesthesia is scavenged and released into the atmosphere without any processing. In the atmosphere it stays and produces deleterious greenhouse effect primarily owing to its long lifetime of 114 years. In addition, it also causes depletion of ozone layer. The green house effect of gases is evaluated and compared with the use of carbon-di-oxide equivalents (CDE). When the effects are considered for 20 years it is termed CDE20.The efforts to reduce these harmful effects can be directed towards reduction/cessation of N2O use, or its post anesthetic processing. The long history of its use in clinical practice and benefits such as analgesia for various procedures; makes it difficult to be completely taken out of usage in the present day anaesthesia practice. Though processing of N2O after use during GA is possible, it's impractical because of cost efficiency. We therefore, have directed our focus on further reducing its consumption while being used for GA. Low- flow anaesthesia has been in practice for the same reason (i.e. to reduce the wastage of gases).

This study is aimed to reduce the N2O consumption even further by employing a novel 'streamed-in' technique of N2O administration during low-flow GA. Conventionally, N2O use is initiated during the initial high fresh gas flows (FGF) before shifting to low-flow ventilation. 'Streamed-in' N2O administration strategy employs initiation of N2O into FGF after the institution of low-flow anaesthesia. Hence, the participants are not exposed to an unconventional drug or a new route of its administration, but an alternate strategy to its conventional use. We aim to evaluate the novel technique of 'streamed-in' N2O during sevoflurane GA for its global warming effects (in terms of CDE20) and its clinical effects ( intraoperative general anaesthesia state, hemodynamic profile) and post operative effects( postoperative nausea vomiting -PONV, postoperative pain profile- numerical rating scale-NRS)

Earliest use of nitrous oxide (N2O) in medical practice dates back to 1884. It aimed at providing analgesia during surgical procedure. Over the years the N2O use for anaesthesia evolved with the knowledge that it has very low anesthetic potential and high minimum alveolar concentration (MAC =104%), and therefore it cannot be used as a sole anesthetic. This led to N2O being used a carrier gas only during inhalational vapor (sevoflurane, isoflurane, desflurane) anaesthesia. The N2O- vapor co-administration not only reduces inhaled vapor requirements but also offers continuous analgesia state during maintenance of anaesthesia. Studies show its use in sedation and analgesia for labor analgesia and other minor procedures especially in pediatric population, such as, venipuncture, venous cannulation, fracture reduction, lumbar puncture, acute pain etc. Further, the use of intraoperative N2O also reduces the incidence of patients developing chronic postoperative pain.

The use of N2O, with attendant application advantages come the disadvantages of having undesirable effect on the patient (diffusion hypoxia, PONV), the medical care provider (megaloblastic anemia, risk of spontaneous abortion, reduced fertility) and environment (global warming). N2O possesses greenhouse effect defined in terms of global warming potential (GWP) \[20 year GWP and 100year GWP - 289 (GWP20) and 298 (GWP100), respectively\] and 'ozone depleting' properties. The above stated effects in conjunction with long life-span of N2O (114 years) in the atmosphere is likely to lead to longstanding negative environmental impact if its use is not stopped/made more efficient. Therefore, there is an absolute need for using N2O more efficiently for reducing effects on the patients, the first to get exposed operative room personnel, and ambient environment at large.

Sevoflurane is an inhalational anesthetic with a sweet smell, fast onset, offset and a good safety profile. Sevoflurane is also a greenhouse gas. Its use in combination with N2O is in practice for the benefits discussed earlier.

Having been in medical use for over 150 years with its various benefits, the use of N2O cannot be expected to be abandoned in the near future. Though steps to reduce anesthetic gas usage with techniques such as low-flow anaesthesia (fresh gas flow-FGF\<alveolar ventilation, arbitrarily taken as 2L/min) and safer carbon-di-oxide absorbers are in vogue; no further/specific exploration has been undertaken. With Sevoflurane, use of fresh gas flows less than 1L/min is not recommended due to concerns surrounding production of Compound A and its nephrotoxic effects (clinically unproven in human ).

Inhalational anesthetics are almost completely excreted through lungs via exhalation without undergoing significant metabolism. Even ex-vivo inhalational agents are not processed, but only collected through scavenging system and released into the atmosphere. 15 The use of N2O with inhalational anesthetics leaves a far greater impact on the environment when compared to their use with air/O2. Though N2O's pound-for- pound impact in terms of global warming (GWP20-289) is less when compared to other inhalational anesthetics in use \[ isoflurane (GWP20-1401), sevoflurane (GWP20-349), desflurane (GWP20-3714)\]; it has a more significant impact on environment mainly because of the much higher consumption volume and also the fact that it is a 'stock' pollutant i.e. has a long lifetime and accumulates overtime. In contrast, inhalational anesthetics which are 'flow' pollutants i.e. have short lifetime and doesn't accumulate as long as new release into atmosphere is kept constant. The global warming impact of gases is evaluated and compared by the CO2 equivalents (CDE) produced. CDE20 (Anesthetic gas quantity in grams \*GWP20), takes into account both the GWP and the quantity of the gas that is produced. The GWP and CDE are calculated for a defined duration of time. Commonly implemented in case of inhalational anesthetic is for 20 years, as the atmospheric lifetime of inhalational anesthetics is less than 20 years.

With the growing concern for global warming and impact of human activity on the earth's ecology; medical fraternity should be at the forefront of new developments that work towards these issues. With the subject at hand the investigators are attempting to reduce the medical use of N2O and in turn its effects on the environment by evaluating a novel method of N2O use. We expect it to reduce the N2O consumption significantly enough to lessen its harmful global ecological impact.

Conventional low-flow anaesthesia with N2O is implemented by using FGF of about ≥4L/m (O2 + N2O) initially. Once desired anesthetic gas composition is attained in the system and the minimum alveolar concentration reflects adequacy of anesthetic depth (i.e. MAC 0.7-1.3), FGF is reduced to the low-flow i.e. ≤1.0 Liters/min.

Though there is evidence to negative environmental effects of inhaled anesthetic vapor and N2O, they have been largely based on theoretical methodology. To the best of our knowledge, till date there are no studies that have evaluated the global warming effects of inhaled GA (with and without N2O) on real use-in patient scenarios. Given that different patients may have different anesthetic uptake (N2O, inhaled vapor) characteristics with different strategies of GA, the consequent environmental effect may be variable, and therefore, must be quantified and controlled.

In this proposed study, the investigators aim to evaluate a novel technique of N2O administration i.e. "streamed-in" administration technique in terms of its global warming impact and clinical effects. Initially, air-O2-sevoflurane is introduced at high FGF of 3.0 L/min. Once the target anesthetic gas concentration is attained in the system i.e. MAC 0.5, FGF is reduced to achieve a low-flow state. At this point N2O is "streamed-in" to add to O2-sevoflurane mixture.

Eligibility Criteria:
Inclusion Criteria:

* Age 18-65 years
* ASA physical status I and II
* Patients undergoing elective non-laparoscopic surgeries of minimum 1 hour duration without use of adjuvant central neuraxial or peripheral nerve block under general anaesthesia

Exclusion Criteria:

* Failure to obtain consent
* Neurological disorders (previous neurosurgery , psychiatric disorders, autonomic system disorders - orthostatic hypotension, transient ischemic attacks )
* Cardiovascular disorders (uncontrolled hypertension, A-V block, sinus bradycardia, congenital heart disease, reduced LV compliance and diastolic dysfunction)
* Hepatorenal insufficiency
* Uncontrolled endocrine disorders (diabetes mellitus, hypothyroidism, hyperthyroidism)
* Electrolyte disturbances (hyponatremia, hypernatremia)
* Pulmonary dysfunction (restrictive /obstructive lung disease)
* Acute /chronic drug dependence /substance abuse
* Closed cavity surgeries (middle ear surgeries, eye surgeries)
* Previous h/o PONV