Global Warming Impact of Nitrous Oxide
Condition: Global Warming Effect of Nitrous Oxide
Study type: Interventional
Phase: Phase 4

Summary: 
      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)
    

Detailed description: 
      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.
    

Intervention name(s): Nitrous oxide; Nitrous oxide; Sevoflurane
Intervention type(s): Drug; Drug; Drug
Intervention description(s): In conventional nitrous oxide carrier group 2% Sevoflurane in O2-N2O (60 % FiO2) @3L/min will be delivered to achieve MAC 0.5.; In streamed-in nitrous oxide carrier group 2% Sevoflurane in O2 -Air (60 % FiO2) will be delivered @3.0L/min to achieve a MAC of 0.5. Then, the FGF will be decreased to 1.0 L (low flow) and N2O will be 'streamed-in' @ 40 %.; Ventilation will be initiated with 2% sevoflurane in all the groups
Intervention MeSH terms: Nitrous Oxide; Sevoflurane
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: One hundred and two patients of either sex, and schedule for elective surgery under general anesthesia (GA) will be randomly divided into three groups of 34-each.
Group 1('Conventional' N2O carrier gas group) Ventilation will be initiated with 2% Sevoflurane in O2-N2O (60 % FiO2) @3L/min to MAC 0.5. Once MAC reaches 0.5, the FGF will be decreased to 1.0L/min.
Group 2 ('Streamed-in' N2O carrier gas group) Ventilation will be initiated with 2% Sevoflurane in O2 -Air (60 % FiO2) @3.0L/min to achieve a MAC of 0.5. Then, the FGF will be decreased to 1.0 L (low flow) and N2O will be 'streamed-in' @ 40 %.
Group 3 (Non-N2O group) Ventilation will be initiated with 2% Sevoflurane in O2-Air (60 % FiO2 @ 3.0L/min) till the time it reaches MAC 0.5. Once MAC 0.5 reached, the FGF is decreased to 1.0L (Low-flow).
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: nitrous oxide; sevoflurane; global warming