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• W4317851214 abstract "I am grateful to Grigoryan et al.1 for their interest in this study2 and their comments. First, in an anesthetized, ventilated population, it is incorrect to simply assume that the respiratory quotient measured will be 0.8, the typical physiologic value determined by steady state metabolism in other situations. Patients are frequently in a state of mild to moderate hyperventilation, producing ongoing washout of the body’s substantial carbon dioxide stores in addition to metabolic carbon dioxide production in the first hour or more after induction. This has been previously shown by us in this population, and average respiratory quotient values in excess of 0.9 are entirely expected.3 Unlike our previous study comparing alveolar deadspace calculations for gases of different solubilities (where the findings would be little affected by the value assumed), a precise measurement of respiratory gas exchange was sought in the current study to achieve maximal precision in the comparison of the adjusted alveolar-arterial partial gradients for nitrous oxide and desflurane using equation 2.This is one example of why “near steady state” most accurately describes the gas exchange state being studied during maintenance phase anesthesia. Grigoryan et al. point out correctly that the equations applied in the study assumed steady state inert gas uptake, which was done for simplicity. However, differentiation of standard equations predicting the typical exponential rate of change of anesthetic gas uptake4 suggests that, after 30 min of anesthesia, less than a 2% relative error in estimation of alveolar-capillary gas uptake rate is expected from using steady state assumptions in the mass balance equations subsequently applied to the adjustment of alveolar-arterial partial pressure gradients for the two gases being compared. This would only make a trivial change to the study findings. Note that there was no significant difference for either gas between uptake measured in the gas and blood phases. The latter is not affected by lung “wash-in” corrections that are part of non–steady state lung gas uptake calculations. The differences in body kinetics between nitrous oxide and desflurane that Grigoryan et al. describe are indeed reflected in the different rates of lung uptake for the two gases clearly demonstrated in the study. The minimal rebreathing expected at the fresh gas flow rate used is accounted for, as calculation of uptake rate measured in the breathing system included the difference between inspired and expired flows (equation A6).The reasons for the choices of inspired concentration of each gas are mentioned in the Materials and Methods. There were no advantages in delivering identical concentrations instead for the two gases, which are measured by infrared gas analyzers calibrated to operate over different clinically relevant concentration ranges. In fact, the best way to deal with the “concentration effect” that the authors allude to was to choose different concentrations that achieved a similar “effective” blood gas partition coefficient (i.e., adjusted for inspired concentration; see reference 14) that corrected for the expected modest difference in the partition coefficient between nitrous oxide and desflurane (listed in table 2).The authors’ concerns about the limits of precision of the measurement device used are dealt with in reference 13. The accuracy of the Datex Capnomac (GE Healthcare, USA) in static gas partial pressure measurement for desflurane has been characterized using precise volumetric standards and found to be within 1% (relative) of predicted, and the resulting accuracy and precision of headspace equilibration measurement of partial pressures in blood were also assessed and were shown to be similar to those achieved by previous workers using gas chromatography. Similar relative accuracy and precision were found for nitrous oxide measurement. However, the foremost prerequisite for measurement of the partial pressure cascade, including alveolar-arterial gradient, for any inert gas is a high degree of linearity of the analyzer over the relevant range. The figure shows this for measurement by the device of a nitrous oxide–desflurane mixture in a gas-tight glass syringe during serial dilution in nitrogen over a 64-fold concentration range that spans the partial pressures encountered in the study. R2 was greater than 0.999 for both gases.The advantages of using a tidal gas monitor like the Capnomac, interfaced with a computer for real-time waveform capture, are substantial when studying alveolar-arterial gradients, as it obviates the practical difficulties in obtaining a reproducible end-expired gas sample uncontaminated by deadspace gas for subsequent gas analysis (by a gas chromatography, for instance). Last, I would take this opportunity to urge all investigators in this field to develop and validate simple assays for blood partial pressure measurement of inhalational agents if intending to study their pharmacology, as the presence of typical alveolar-arterial partial pressure gradients for inhalational anesthetics makes the commonly practiced reliance on end-tidal gas concentration measurements inadequate to accurately characterize their pharmacokinetics for many purposes.This work was supported by Project Grant DJ17/006 from the Australian and New Zealand College of Anaesthetists Research Foundation (Victoria, Australia).Dr. Peyton has received research consultancy payments from Maquet Critical Care/Getinge (Stockholm, Sweden) for an unrelated project." @default.
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• W4317851214 date "2023-01-18" @default.
• W4317851214 modified "2023-09-27" @default.
• W4317851214 title "Diffusion Limitation of Volatile Anesthetic Uptake: Reply" @default.
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• W4317851214 doi "https://doi.org/10.1097/aln.0000000000004447" @default.
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