The Second Gas Effect in Anesthesia
The second gas effect occurs when nitrous oxide enhances the uptake of volatile anesthetics administered simultaneously, resulting in a more rapid increase in alveolar and arterial concentrations of the second gas. This effect is greater in blood than in expired gas, persists well into the maintenance phase of anesthesia, and is most pronounced with less soluble volatile agents currently in use. 1, 2
Mechanism of the Second Gas Effect
- The second gas effect is based on the rapid uptake of nitrous oxide causing a concentrating effect on other gases present in the alveoli 3
- When a high concentration of nitrous oxide (typically 65-70%) is administered, its rapid absorption creates a net gas volume loss in the alveoli 1
- This volume contraction concentrates the remaining gases, including volatile anesthetics, increasing their partial pressure and accelerating their uptake 4
- The effect is more pronounced with higher concentrations of nitrous oxide (65% vs 5%) 3
Factors Affecting the Magnitude of the Second Gas Effect
- Solubility of the second gas: Less soluble agents (like desflurane) show a more pronounced second gas effect in blood compared to more soluble agents (like diethyl ether) 2
- Ventilation-perfusion mismatch: Increasing ventilation-perfusion mismatch enhances the second gas effect in blood while simultaneously decreasing it in the gas phase 2, 4
- Concentration of nitrous oxide: Higher inspired concentrations of nitrous oxide produce a greater second gas effect 3
- Duration: The effect persists well into the maintenance phase of anesthesia, not just during induction 1
Clinical Implications
- The second gas effect accelerates induction of anesthesia when nitrous oxide is used with volatile agents 3
- Gas-based minimum alveolar concentration (MAC) readings may underestimate the depth of anesthesia during nitrous oxide anesthesia with volatile agents 2
- The effect is most clinically significant with less soluble agents like desflurane and sevoflurane 2
- In pediatric patients, the second gas effect has been demonstrated with sevoflurane and nitrous oxide, though the effect may be briefer due to sevoflurane's higher solubility compared to desflurane 5
Environmental Considerations
- Current guidelines recommend minimizing nitrous oxide use due to environmental concerns 6, 7
- The French Society of Anesthesia and Resuscitation strongly recommends not utilizing nitrous oxide when choosing an inhalational anesthetic, due to its greenhouse gas properties 6
- When nitrous oxide must be used, it should be delivered in a bottle rather than a canister and delivery circuit to reduce environmental impact 6
- Sevoflurane is preferred over desflurane or isoflurane for environmental reasons when an inhalational agent is required 6, 7
Practical Considerations
- Low fresh gas flow techniques should be employed when using inhaled anesthetics to reduce environmental impact 6, 7
- Monitoring depth of anesthesia in association with end-tidal anesthetic concentration helps reduce consumption of anesthetic vapors 6
- The use of Entonox (50:50 mixture of oxygen and nitrous oxide) should be avoided if possible in patients at risk of hypercapnic respiratory failure 6
- When equal clinical benefit is expected, anesthesia professionals may choose either inhaled vapors or total intravenous anesthesia with propofol, recognizing that inhaled agents have environmental impact through greenhouse gas emissions while propofol is ecotoxic for water and soils 6, 8
Physiological Nuances
- The alveolar-arterial partial pressure difference for gases may be reversed during uptake of highly insoluble gases when administered with nitrous oxide 1
- Net uptake of gases administered with nitrous oxide may proceed against an alveolar-arterial partial pressure gradient 1
- Despite equal solubility in blood, the rise in FA/FI (alveolar/inspired concentration ratio) for nitrous oxide exceeds that for desflurane, possibly due to differences in tissue solubilities and intertissue diffusion 3