II. Indications

  1. Procedural Sedation (esp. pediatrics)
    1. Low intensity procedures (e.g. Lumbar Puncture, Laceration Repair, minor Fracture reduction)
  2. Moderate analgesia
    1. Best used in combination with Local Anesthesia (e.g. local infiltration, Hematoma Block)

III. Contraindications (related to gas expansion risks)

IV. History

  1. First used for Anesthesia in U.S. in 1845
  2. Used in a majority of pediatric dental offices

V. Mechanism

  1. Nitrous Oxide is a colorless, tasteless gas
  2. Effects Opioid spinal modulators, GABA Receptors, NMDA receptors
  3. Also releases endorphins

VI. Pharmacokinetics

  1. Rapidly absorbed in lung and cleared from lung
  2. Excreted unchanged (not metabolized) primarily from lung within one minute of inhalation
    1. Poorly soluble in blood
  3. Onset: 2-3 minutes
  4. Duration: 3-5 minutes
    1. Rapidly off-loads with oxygen (often given for 5 minutes after procedure)
  5. Effects
    1. Mild anxiolysis: <50% Nitrous Oxide
    2. Analgesia: 50-70% Nitrous Oxide
    3. Amnesia
  6. Minimum Alveolar Concentration (MAC): 105.0%
    1. Nitrous Oxide MAC is much higher than other inhalation Anesthetics (e.g. Isoflurane)
    2. With a high MAC, Nitrous Oxide is a poor general Anesthetics alone, but offers good lower level sedation

VII. Adverse Effects

  1. Light Headedness
  2. Somnolence
  3. Confusion
  4. Paresthesias
  5. Nausea or Vomiting (1-2% of cases)
    1. Vomiting is uncommon unless concurrent Opioids are used
  6. Inadequate sedation (1.2% of cases)
  7. Airway obstruction or Hypoxia (0.25% of cases)
    1. More common with concurrent Opioids or Benzodiazepines

VIII. Safety

  1. Among the safest sedation agents with proper use and monitoring (ACEP, 1984)
  2. Airway obstruction or Hypoxia is rare (0.25% of cases)
  3. Has not been associated with apnea
  4. Hemodynamically stable without effects on Heart Rate or Blood Pressure
  5. Very rare mortality (case reports)
  6. No Allergic Reactions reported
  7. No pregnancy data, and not recommended in first or second trimester
    1. Considered likely safe in third trimester
  8. No delay in Lactation
  9. Not considered Procedural Sedation unless combined with other agents (e.g. Fentanyl, Midazolam)
  10. Does not require cardiac monitoring, End-Tidal CO2 or Intravenous Access
    1. Pulse Oximetry is typically adequate monitoring for Nitrous Oxide

IX. Preparation

  1. General equipment
    1. Oxygen supply
    2. Wall suction
    3. Airway equipment
  2. Educate patient on use of mask
    1. Patient instructed to take deeper breaths if feels more pain
  3. Nitrous Oxide delivery device
    1. Full Face Mask or Nasal mask (may be scented)
    2. Delivery mix: 50:50 to 70:30 mix of Nitrous Oxide and oxygen
      1. Preferred mix appears to be 70:30
      2. Typically portable unit with Nitrous Oxide tanks, and attached to wall oxygen
    3. Device should have audible alarms, flow control and scavenger functionality (suction)
      1. Scavenger functionality prevents bystander exposure to Nitrous Oxide
    4. Does not require a medical gas vacuum system

X. Dosing

  1. Goal Nitrous Oxide effects (expect onset within 2-3 min of starting Nitrous Oxide)
    1. Apathy
    2. Somnolence
    3. Still responds to verbal stimuli
  2. Start with total liter flow estimation
    1. Child: 4-5 L/min
    2. Adult: 6-7 L/min
    3. Watch reservoir bag while on oxygen only, and goal inflation is 2/3 full (not collapsed and not full)
  3. Initiate Nitrous Oxide
    1. Start 10-15% Nitrous Oxide and increase every couple of minutes to effect (see above)
    2. Patient asked to breath normally through their nose and to relax
    3. Prepare patient that they may have arms and legs
  4. Titrate Nitrous Oxide
    1. Stop agent for Nausea (and allow to dissipate over 2-3 minutes, and then re-start)
    2. Decrease Nitrous Oxide if Agitation occurs
    3. Oxygen reverses effects if too much sedation
  5. Self-titration method
    1. Patient holds mask to their own face
    2. As sedation increases, the mask drops away
    3. When they awaken again, they replace the mask to once again increase sedation

XI. References

  1. Acker, Koval and Leeper (2017) Crit Dec Emerg Med 31(4): 3-13
  2. Cordle (2016) Nitrous Oxide Lecture, ACEP PEM Conference, attended 3/9/2016
  3. Lapietra and Swaminathan in Swadron (2022) EM:Rap 22(3): 6-8

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Ontology: Nitrous Oxide (C0028215)

Definition (NCI) A naturally occurring gas that is colorless and non flammable. It can be manufactured and used for a variety of things such as a pharmacologic agent to produce anesthesia, a food additive as a propellant, and an additive to fuels to increase available oxygen in combustion.
Definition (CSP) "laughing gas"; N2O.
Definition (MSH) Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream.
Concepts Biologically Active Substance (T123) , Pharmacologic Substance (T121) , Inorganic Chemical (T197)
MSH D009609
SnomedCT 388185005, 273959001, 111132001
LNC LP100617-2, MTHU035878
English Oxide, Nitrous, Laughing Gas, Gas, Laughing, nitrous oxide, Nitrogen oxide (N2O), nitrous oxide (medication), NITROUS OXIDE GAS, NITROUS OXIDE @ @ GAS, Dinitrogen Monoxide, Nitrogen Protoxide, Nitrous Oxide [Chemical/Ingredient], NITROUS OXIDE, nitrous oxide gas, laughing gas, Nitrous oxide, Nitrous oxide gas, Dinitrogen monoxide, Laughing gas, N2O - Nitrous oxide, Nitrous oxide (product), Nitrous oxide (substance), Nitrous Oxide
French N2O, Oxyde nitreux, Monoxyde de diazote, Gaz hilarant, Protoxyde d'azote
Swedish Lustgas
Czech oxid dusný
Finnish Typpioksiduuli
Russian AZOTA III OKSID, AZOTISTYI ANGIDRID, VESELIASHCHII GAZ, AZOTA ZAKIS', ZAKIS' AZOTA, АЗОТА III ОКСИД, АЗОТА ЗАКИСЬ, АЗОТИСТЫЙ АНГИДРИД, ВЕСЕЛЯЩИЙ ГАЗ, ЗАКИСЬ АЗОТА
Italian Gas esilarante, Ossido nitroso
Polish Podtlenek azotu
Japanese 笑気, 亜酸化窒素, 一酸化二窒素, 酸化二窒素
Norwegian Lystgass, Dinitrogenoksid, Lattergass
Spanish óxido nitroso (producto), óxido nitroso (sustancia), óxido nitroso, Óxido Nitroso
German Distickstoffoxid
Portuguese Óxido Nitroso