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A systematic review of clinical trials confirms that including nitrous oxide in the gas mixture for general anaesthesia has minor short-term benefits and does not impact most patient safety outcomes. However, no risk-benefit analysis of nitrous oxide should ignore its known environmental effects. If continued nitrous oxide use is supported, strategies to minimise and monitor the contribution of medical nitrous oxide to global warming are vital. [ABSTRACT FROM AUTHOR]

We have investigated the elimination of inert gases in the lung during the elimination of nitrous oxide (N2O) using a two‐step mathematical model that allows the contribution from net gas volume expansion, which occurs in Step 2, to be separated from other factors. When a second inert gas is used in addition to N2O, the effect on that gas appears as an extra volume of the gas eliminated in association with the dilution produced by N2O washout in Step 2. We first considered the effect of elimination in a single gas‐exchanging unit under steady‐state conditions and then extended our analysis to a lung having a log‐normal distribution of ventilation and perfusion. A further increase in inert gas elimination was demonstrated with gases of low solubility in the presence of the increased ventilation‐perfusion mismatch that is known to occur during anesthesia. These effects are transient because N2O elimination depletes the input of that gas from mixed venous blood to the lung, thereby rapidly reducing the magnitude of the diluting action. [ABSTRACT FROM AUTHOR]

In the three‐compartment model of lung ventilation‐perfusion heterogeneity (VA/Q scatter), both Bohr dead space and shunt equations require values for central "ideal" compartment O2 and CO2 partial pressures. However, the ideal alveolar gas equation most accurately calculates mixed (ideal and alveolar dead space) PAO2. A novel "modal" definition has been validated for ideal alveolar CO2 partial pressure, at the VA/Q ratio in a lung distribution where CO2 elimination is maximal. A multicompartment computer model of physiological, lognormal distributions of VA and Q was used to identify modal "ideal" PAO2, and find a modification of the alveolar gas equation to estimate it across a wide range of severity of VA/Q heterogeneity and FIO2. This was then validated in vivo using data from a study of 36 anesthetized, ventilated patients with FIO2 0.35–80. Substitution in the alveolar gas equation of respiratory exchange ratio R with modalR=R–1–PEtCO2/PaCO2$$ \kern0.5em \mathrm{modalR}=\mathrm{R}\hbox{--} \left(1\hbox{--} \mathrm{PEtC}{\mathrm{O}}_2/\mathrm{P}{\mathrm{aCO}}_2\right) $$ achieved excellent agreement (r2 = 0.999) between the calculated ideal PAO2 and the alveolar‐capillary Pc'O2 at the modal VO2 point ("modal" Pc'O2), across a range of log standard deviation of VA 0.25–1.75, true shunt 0%–20%, overall VA/Q 0.4–1.6, and FIO2 0.18–1.0, where the modeled PaO2 was over 50 mm Hg. Modal ideal PAO2 can be reliably estimated using routine blood gas measurements. [ABSTRACT FROM AUTHOR]

Previously, we reviewed 1052 randomized-controlled trial abstracts presented at the American Society of Anesthesiologists annual meetings from 2001–2004. We found significant positive publication bias in the period examined, with the odds ratio for abstracts with positive results proceeding to journal publication over those with null results being 2.01 [95% confidence interval: 1.52, 2.66; P < 0.001]. Mandatory trial registration was introduced in 2005 as a required standard for publication. We sought to examine whether mandatory trial registration has decreased publication bias in the anesthesia and perioperative medicine literature. We reviewed all abstracts from the 2010–2016 American Society of Anesthesiologists meetings that reported on randomized-controlled trials in humans. We scored the result of each abstract as positive or null according to a priori definitions. We systematically searched for any subsequent publication of the studies and calculated the odds ratio for journal publication, comparing positive vs null studies. We compared the odds ratio from the 2010–2016 abstracts (post-mandatory trial registration) with the odds ratio from the 2001–2004 abstracts (pre-mandatory trial registration) as a ratio of odds ratios. We defined a 33% decrease in the odds ratio as significant, corresponding to a new odds ratio of 1.33. We reviewed 9789 abstracts; 1049 met inclusion criteria as randomized-controlled trials, with 542 (51.7%) of the abstracts going on to publication. The odds ratio for abstracts with positive results proceeding to journal publication was 1.28 [95% CI: 0.97, 1.67; P = 0.076]. With adjustment for sample size and abstract quality, the difference in publication rate between positive and null abstracts was statistically significant (odds ratio 1.34; 95% CI: 1.02, 1.76; P = 0.037). The ratio of odds ratios, comparing the odds ratio from the 2010–2016 abstracts (post-mandatory trial registration) to the odds ratio from the 2001–2004 abstracts (pre-mandatory trial registration), was 0.63 (95% CI: 0.43, 0.93); P = 0.021). We present the first study in the anesthesia and perioperative medicine literature that examines and compares publication bias over two discrete periods of time, prior to and after the implementation of mandatory trial registration. Our results suggest that the amount of publication bias has decreased markedly following implementation of mandatory trial registration. However, some positive publication bias in the anesthesia and perioperative medicine literature remains. [ABSTRACT FROM AUTHOR]

Mandatory prospective trial registration was introduced in 2005 to reduce publication bias and selective outcome reporting. In this study, we measured the proportion of prospective trial registration in randomized controlled trials in the anesthesia literature after this introduction, discrepancies between these trial protocols and subsequent publications, the association between being prospectively registered and reporting positive or negative results, and between being prospectively registered and achieving publication. We reviewed all abstracts from the American Society of Anesthesiologists annual meetings between 2010–2016 and included randomized controlled trials in humans. The abstract conclusions were scored as positive or negative according to predetermined definitions. We conducted a systematic search for trial registration and subsequent publication. Of the 9789 abstracts reviewed, 1070 abstracts were included. 222 (21%) of these abstracts had undergone prospective trial registration. 168/222 (76%) had a corresponding journal publication. 81(48%) had a major discrepancy between registration and publication. 149 (67%) of the abstracts with registration had positive outcomes compared with 616 (73%) of those without (Odds Ratio 0.77; 95% CI: 0.56 to 1.06; P = 0.105). Abstracts that had been registered were more likely to proceed to publication than those that had not (Odds Ratio 3.82; 95% CI 2.73 to 5.35; P < 0.001). The proportion of randomized controlled trials being prospectively registered in anesthesia remains low. Discrepancies between registry entries and corresponding journal publications are common. There was no association between prospective trial registration and subsequent positive outcomes. There was a strong association between prospective trial registration and the likelihood of progression to journal publication. [ABSTRACT FROM AUTHOR]

Under the three-compartment model of ventilation-perfusion (VA=Q) scatter, Bohr-Enghoff calculation of alveolar deadspace fraction (VDA/VA) uses arterial CO2 partial pressure measurement as an approximation of "ideal" alveolar CO2 (ideal PACO2). However, this simplistic model suffers from several inconsistencies. Modeling of realistic physiological distributions of V A and Q instead suggests an alternative concept of "ideal" alveolar gas at the VA=Q ratio where uptake or elimination rate of a gas is maximal. For alveolar-capillary partial pressure, this "modal" point equals the mean of expired alveolar and arterial partial pressures, regardless of V A=Q scatter severity or overall V A=Q. For example, modal ideal PACO2 can be estimated from the following equation: Estimated modal ideal PACO2 = (PACO2 + PaCO2)/2 Using a multicompartment computer model of log-normal distributions of VA and Q, agreement of this estimate with the modal ideal PACO2 located at the VA=Q ratio of maximal compartmental VCO2 was assessed across a wide range of severity of VA=Qscatter and overall VA=Q ratio. Agreement of VDA/VA for CO2 from the Bohr equation using modal ideal PCO2, with that using the estimated value was also assessed. Estimated modal ideal PACO2 agreed closely with modal ideal PACO2, intraclass correlation (ICC) > 99.9%. There was no significant difference between VDA/VA using either value for ideal PACO2. Modal ideal PACO2 reflects a physiologically realistic concept of ideal alveolar gas where there is maximal gas exchange effectiveness in a physiological distribution of VA=Q, which is generalizable to any inert gas and is practical to estimate from arterial and end-expired CO2 partial pressures. [ABSTRACT FROM AUTHOR]

The second gas effect occurs when high inspired concentrations of a first gas, usually nitrous oxide, enhance the uptake of other gases administered simultaneously. The second gas effect is greater in blood than in the gas phase, persists well into the period of nitrous oxide maintenance anesthesia, increases as the degree of ventilation-perfusion mismatch increases, and is most pronounced with the low soluble agents in current use. Yet, how low gas solubility and increased ventilation-perfusion mismatch can combine to improve gas transfer remains unclear, which is the focus of the present study. Specifically, we have used a two-step model of gas exchange to separate the effect of gas volume contraction, which accompanies the first gas uptake, from other factors. Step 1 involves the uptake of the second gas at constant volume. Contraction of gas volume takes place in step 2 and is most effective in transferring further amounts of gas to blood if the volume of second gas exposed to the contraction is maximized, i.e., if the loss of second gas in step 1 is minimized. Minimization depends on having a gas with a low solubility in blood and increases as the degree of ventilation-perfusion mismatch increases. The effectiveness of the contraction also requires a favorable alignment with the retained second gas. Alignment depends on the solubility of both gases and the degree of ventilationperfusion mismatch. The model is fully consistent with classical concepts of gas exchange. NEW & NOTEWORTHY Gas exchange in the lung can always be represented as the sum of two components: gas exchange at constant volume followed by gas exchange on volume correction. Using this sequence to study the second gas effect, low gas solubility and increased ventilation-perfusion mismatch are shown to act together to enhance second gas uptake. While appearing to contravene classical concepts of gas exchange, a detailed theoretical analysis shows it is fully consistent with these concepts. [ABSTRACT FROM AUTHOR]

Lung gas exchange efficiency deteriorates during general anaesthesia due to ventilation-perfusion (V/Q) scatter. Propofol total intravenous anaesthesia (TIVA) may preserve V/Q matching better than inhalational agents. We compared V/Q matching in patients randomized to either TIVA or sevoflurane anaesthesia, using deadspace and shunt measurements and the MIGET (Multiple Inert Gas Elimination Technique). Baseline arterial blood and mixed expired gas sampling was done before induction and repeated after one to two hours of relaxant general anaesthesia in 20 patients, supine with controlled ventilation at an FiO2 of 0.3 and a target end-tidal PCO2 of 30-35 mmHg. Blood samples for MIGET were processed after headspace equilibration by gas chromatography. The primary endpoint was a comparison of the two groups in the change from baseline of absolute difference between log standard deviation of ventilation and blood flow distributions (@(rV-rQ)). Deadspace fraction increased and PaO2/FiO2 ratio decreased across both groups overall with anaesthesia, but change in deadspace was not different between groups (mean (standard deviation, SD) sevoflurane 21.8% (11.7%) versus TIVA 20.5% (10.6%), P=0.601). Change in PaO2/FiO2 ratio was also similar between groups (mean (SD) sevoflurane -51.9 (69.1) mmHg versus TIVA -78.3 (76.9) mmHg, P=0.43), as was change in shunt fraction (dQs/Qt mean (SD) sevoflurane -5.1% (12.6%) versus TIVA 0.4% (7.7%), P=0.174). The primary endpoint @(rV-rQ) was not different between sevoflurane and propofol TIVA groups (mean (SD) 0.17 (0.81) versus 0.17 (0.29), P=0.94). TIVA did not better preserve V/Q matching in patients undergoing anaesthesia with controlled ventilation compared with sevoflurane. [ABSTRACT FROM AUTHOR]

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 steadystate 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. [ABSTRACT FROM AUTHOR]

Purpose: Many areas of medicine have shown bias towards the publication of studies with positive results. To estimate publication bias in the anesthesia literature, we reviewed all abstracts presented at the American Society of Anesthesiologists (ASA) annual meetings over a four-year period and compared study results (positive vs negative) with publication outcomes.Methods: This review included all abstracts from the 2001-2004 ASA annual meetings performed as randomized-controlled trials in humans. We scored their outcome results as positive or negative and assessed abstract quality using a 13-point scoring system. We then performed a systematic literature search to identify any subsequent publication of the studies and calculated the relative risk (RR) for journal publication by comparing positive vs negative studies.Results: Of 5,918 abstracts reviewed, 1,052 met inclusion criteria, and 564 (53.6%) of the abstracts proceeded to publication. The RR for abstracts with positive results proceeding to journal publication was 1.42 (95% confidence interval, 1.22 to 1.66; P < 0.001). This result did not change significantly after adjusting for study size and abstract quality score during logistic regression modelling. There was no significant difference in the abstract quality score between positive vs negative studies or between abstracts proceeding vs not proceeding to publication.Conclusions: Approximately half of the ASA annual meeting abstracts proceed to publication. After adjustment for study quality and size, abstracts with positive results were more likely to proceed to journal publication than those with negative results, suggesting publication bias in the anesthesia literature. [ABSTRACT FROM AUTHOR]