Second Gas Effect Research Articles

Effect of net gas volume changes on alveolar and arterial gas partial pressures in the presence of ventilation-perfusion mismatch.

The second gas effect (SGE) occurs when nitrous oxide enhances the uptake of volatile anesthetics administered simultaneously. Recent work shows that the SGE is greater in blood than in the gas phase, that this is due to ventilation-perfusion mismatch, that as mismatch increases, the SGE increases in blood but is diminished in the gas phase, and that these effects persist well into the period of nitrous oxide maintenance anesthesia. These modifications of the SGE are most pronounced with the low soluble agents in current use. We investigate further the effect of net gas volume loss during nitrous oxide uptake on low concentrations of other gases present using partial pressure-solubility diagrams. The steady-state equations of gas exchange were solved assuming a log-normal distribution of ventilation-perfusion ratios using Lebesgue-Stieltjes integration. It was shown that under these conditions the classical partial pressure-solubility diagram must be modified, that for currently used volatile anesthetic agents the alveolar-arterial partial pressure difference is less than that predicted in the past, and that the alveolar-arterial partial pressure difference may even be reversed during uptake in the case of highly insoluble gases such as sulfur hexafluoride. Comparing this with the situation described previously for nitrogen in steady-state air breathing, we show that for nitrogen, the direction of the alveolar-arterial gradient is opposite to the direction of net gas volume movement. Although gas uptake with ventilation-perfusion inequality exceeding that when matching is optimal is shown to be possible, it is less likely than alveolar-arterial partial pressure reversal. NEW & NOTEWORTHY Net uptake of gases administered with nitrous oxide may proceed against an alveolar-arterial partial pressure gradient. The alveolar-arterial gradient for nitrogen in the steady-state breathing air depends not only on the existence of a distribution of ventilation-perfusion ratios in the lung but also on the presence of a net change in gas volume and is opposite in direction to the direction of net gas volume uptake.

John Snow and the First Second-Gas Effect

In 1847, British anesthesia pioneer John Snow (1813-1858) observed that patients did not manifest cyanosis during induction with hypoxic mixtures of ether vapor in air. He hypothesized a molecular mechanism that would be understood over a century later as the second gas effect.

Does Nitrous Oxide Affect Bispectral Index and State Entropy When Added to a Propofol Versus Sevoflurane Anesthetic?

In earlier studies, nitrous oxide (N2O) did not affect bispectral index (BIS) or state entropy (SE) when administered as the sole anesthetic agent. We investigated the effect of adding N2O to sevoflurane or propofol anesthesia on BIS and SE. A total of 28 patients were randomized to receive general anesthesia using either 2% sevoflurane or 120 mcg/kg/min propofol during surgery. After 20 minutes of stable anesthetic and surgical conditions (baseline), 60% N2O was added for 20 minutes. Another 20 minutes was allowed for washout after N2O was discontinued. Sevoflurane concentration was closely monitored using the standard end-tidal gas analysis and vaporizer output was constantly adjusted to offset the second-gas effect caused by the addition and discontinuation of N2O. Mean values for BIS and SE were calculated for the last 5 minutes of the baseline, nitrous oxide, and washout periods. In the propofol group, BIS and SE values in baseline versus N2O periods were 40±10 versus 39±10 and 43±11 versus 43±12, respectively (mean±SD, P>0.05). In the sevoflurane group, addition of N2O decreased both BIS (36±7 to 32±7, P<0.001) and SE (37±10 to 31±11, P=0.001). The magnitude of change from the baseline in BIS and SE in the sevoflurane group was 3.6±3.8 (95% CI: 0.8-6.5) and 6.1±5.5 (95% CI: 3.7-8.6), respectively. Average baseline and washout values of BIS and SE were not different in both groups (P>0.05). N2O decreased both BIS and SE when added to sevoflurane, but not propofol. The observed changes in the sevoflurane group were not clinically significant. Decreases in BIS and SE in the sevoflurane group could result from a true additive effect and second-gas effect of N2O that was unaccounted for despite a meticulous titration of sevoflurane using end-tidal gas monitoring.

Large volume N2O uptake alone does not explain the second gas effect of N2O on sevoflurane during constant inspired ventilation

The second gas effect (SGE) is considered to be significant only during periods of large volume N(2)O uptake (VN(2)O); however, the SGE of small VN(2)O has not been studied. We hypothesized that the SGE of N(2)O on sevoflurane would become less pronounced when sevoflurane administration is started 60 min after the start of N(2)O administration when VN(2)O has decreased to approximately 125 ml min(-1), and that the kinetics of sevoflurane under these circumstances would become indistinguishable from those when sevoflurane is administered in O(2). Seventy-two physical status ASA I-II patients were randomly assigned to one of six groups (n=12 each). In the first four groups, sevoflurane (1.8% vaporizer setting) administration was started 0, 2, 5 and 60 min after starting 2 litre min(-1) O(2) and 4 litre min(-1) N(2)O, respectively. In the last two groups, sevoflurane (1.8 or 3.6% vaporizer setting) was administered in 6 litre min(-1) O(2). The ratios of the alveolar fraction of sevoflurane (Fa) over the inspired fraction (Fi), or Fa/Fi, were compared between the groups. Sevoflurane Fa/Fi was larger in the N(2)O groups than in the O(2) groups, and it was identical in all four N(2)O groups. We confirmed the existence of a SGE of N(2)O. Surprisingly, when using an Fa of 65% N(2)O, the magnitude of the SGE was the same with large or small VN(2)O. The classical model and the graphical representation of the SGE alone should not be used to explain the magnitude of the SGE. We speculate that changes in ventilation/perfusion inhomogeneity in the lungs during general anaesthesia result in a SGE at levels of VN(2)O previously considered by most to be too small to exert a SGE.

The Second Gas Effect is Not Statistically Valid

The Second Gas Effect is Not Statistically Valid

Concentration and second-gas effects in the water analogue

The water analogue provides a visual model of the process of anaesthetic exchange. In the standard version, a single pipe connects the mouth container to the lung container and the conductance of this mouth-lung pipe is proportional to alveolar ventilation. This implies that inspired and expired ventilations are equal. In fact, with high inspired concentrations of nitrous oxide, early rapid uptake of gas by solution leads to a substantial difference between inspired and expired ventilation which in turn leads to concentration and second-gas effects. It is shown that by representing inspired and expired ventilations separately, and keeping one of them constant while varying the other to compensate for rapid uptake, concentration and second-gas effects are reproduced in the water analogue. Other means of reproducing the effects are reported but we believe that the first method is the most realistic and the most appropriate for teaching.

A System Model for Closed-circuit Inhalation Anesthesia I. Computer Study

Developing a custom computer program to simulate the uptake, distribution, and elimination of inhalational anesthetics allows the anesthesiologist to address specific problems, but extensive skills are required to translate the involved processes first into a set of mathematical equations and then into a satisfactory computer program. The first step is often facilitated by solutions offered in the literature. The second step demands computer proficiency that is often not available, but this problem can be obviated by means of a special-purpose simulation language (SPSL). We therefore constructed a model for closed-circuit inhalation anesthesia with the aid of the block-structured SPSL TUTSIM. Noticeable differences with previous models are that the linear, 14-compartment basic model does not assume a constant alveolar concentration and mimics circulation times through the use of blood pools. Advanced features of the SPSL were used to develop variants of the basic model to simulate feedback-controlled isoflurane administration, nitrous oxide uptake, and the impact of a nonlinearity by incorporating the effect of enflurane on cardiac output. Two variants were concatenated to form a multiple model showing the concentration and second-gas effects. The model was capable of reproducing the anesthetic uptake from previous experimental studies for nitrous oxide. After its validation for other anesthetic agents, the model can be used for clinical, teaching, and research purposes. The SPSL freed the authors from the problems associated with computer programming and allowed them to concentrate on the structure of the model.

Extent and duration of the nitrous oxide second-gas effect on oxygen.

Extent and duration of the nitrous oxide second-gas effect on oxygen.

The effect of nitrous oxide on alveolar carbon dioxide tension: a second-gas effect.

The effect of nitrous oxide on alveolar carbon dioxide tension: a second-gas effect.