Nitrous oxide diffusion and the second gas effect on emergence from anesthesia.

BACKGROUND: Rapid elimination of nitrous oxide from the lungs at the end of inhalational anesthesia dilutes alveolar oxygen, producing "diffusion hypoxia." A similar dilutional effect on accompanying volatile anesthetic agent has not been evaluated and may impact the speed of emergence. METHODS: Twenty patients undergoing surgery were randomly assigned to receive an anesthetic maintenance gas mixture of sevoflurane adjusted to bispectral index, in air-oxygen (control group) versus a 2:1 mixture of nitrous oxide-oxygen (nitrous oxide group). After surgery, baseline arterial and tidal gas samples were taken. Patients were ventilated with oxygen, and arterial and tidal gas sampling was repeated at 2 and 5 min. Arterial sampling was repeated 30 min after surgery. Sevoflurane partial pressure was measured in blood by the double headspace equilibration technique and in tidal gas using a calibrated infrared gas analyzer. Time to eye opening and time extubation were recorded. The primary endpoint was the reduction in sevoflurane partial pressures in blood at 2 and 5 min. RESULTS: Relative to baseline, arterial sevoflurane partial pressure was 39% higher at 5 min in the control group (P < 0.04) versus the nitrous oxide group. At 30 min the difference was not statistically significant. Time to eye opening (8.7 vs. 10.1 min) and time to extubation (11.0 vs.13.2 min) were shorter in the nitrous oxide group versus the control group (P < 0.04). CONCLUSIONS: Elimination of nitrous oxide at the end of anesthesia produces a clinically significant acceleration in the reduction of concentrations of the accompanying volatile agents, contributing to the speed of emergence observed after inhalational nitrous oxide anesthetic.

Continuous measurement of multiple inert and respiratory gas exchange in an anaesthetic breathing system by continuous indirect calorimetry.

A method was tested which permits continuous monitoring from a breathing system of the rate of uptake of multiple gas species, such as occurs in patients during inhalational anaesthesia. The method is an indirect calorimetry technique which uses fresh gas rotameters for control, regulation and measurement of the gas flows into the system, with continuous sampling of mixed exhaust gas, and frequent automated recalibration to maintain accuracy. Its accuracy was tested in 16 patients undergoing pre-cardiopulmonary bypass coronary artery surgery, breathing mixtures of oxygen/air and sevoflurane with/without nitrous oxide, by comparison with the reverse Fick method. Overall mean bias [95% confidence interval (CI)] of rate of uptake was 17.9 [7.3 to 28.5] ml min(-1) for oxygen, 0.04 [-0.42 to 0.50] ml min(-1) for sevoflurane, 10.9 [-16.1 to 37.8] for CO(2), and 8.8 [-14.8 to 32.4] ml min(-1) for nitrous oxide where present. The method proved to be accurate and precise, and allows continuous monitoring of exchange of multiple gases using standard gas analysis devices.

Magnitude of the second gas effect on arterial sevoflurane partial pressure.

BACKGROUND: A number of studies have demonstrated a faster rate of increase in end-expired partial pressure as a fraction of inspired (Pa/Pi) for volatile agents in the presence of high concentrations of nitrous oxide, consistent with the second gas effect. However, no study has demonstrated a similar effect on arterial blood concentrations. METHODS: The authors compared arterial and end-tidal partial pressures of sevoflurane (Pa/Pisevo and Pa/Pisevo) in 14 patients for 30 min after introduction of either 70% nitrous oxide or nitrous oxide-free gas mixtures to determine the magnitude of the second gas effect. Blood partial pressures were measured using a double headspace equilibration technique. RESULTS: Both Pa/Pisevo and Pa/Pisevo were significantly higher in the nitrous oxide group than in the control group (P < 0.001 on two-way analysis of variance). This difference was significantly greater (P < 0.05) for Pa/Pisevo (23.6% higher in the nitrous oxide group at 2 min, declining to 12.5% at 30 min) than for Pa/Pisevo (9.8% higher in the nitrous oxide group at 2 min) and was accompanied by a significantly lower Bispectral Index score at 5 min (40.7 vs. 25.4; P = 0.004). CONCLUSION: Nitrous oxide uptake exerts a significant second gas effect on arterial sevoflurane partial pressures. This effect is two to three times more powerful than the effect on end-expired partial pressures. The authors explain how this is due to the influence of ventilation-perfusion scatter on the distribution of blood flow and gas uptake in the lung.

Measurement of anesthetics in blood using a conventional infrared clinical gas analyzer.

BACKGROUND: Measurement of the partial pressure of volatile anesthetics in blood is usually done using a "headspace equilibration" method with gas chromatography. However, it is not often performed in clinical studies because of the technical, equipment, and logistic requirements. To improve the accessibility of this measurement, we tested the use of a common infrared clinical gas analyzer, the Datex-Ohmeda Capnomac, for this purpose. METHODS: After characterization of the linearity of the device in measuring the volatile anesthetic concentration in the presence of nitrous oxide, carbon dioxide, and water vapor, blood was tonometered with known concentrations of sevoflurane (actual value between 0.5% and 5.0%) in oxygen and oxygen/nitrous oxide mixtures, as well as mixtures of isoflurane and desflurane in oxygen. RESULTS: Mean bias (standard deviation) overall for sevoflurane in oxygen relative to the tonometered reference partial pressure was -4.5 (4.8%) of the actual concentration. This was not altered significantly by measurement in 40% oxygen/60% nitrous oxide. For isoflurane and desflurane it was -3.9 (3.3%) and -4.6 (3.8%), respectively, of the actual concentration. CONCLUSIONS: The accuracy and precision of measurement of volatile anesthetic gas partial pressures in blood by a double headspace equilibration technique, using a clinical infrared gas analyzer, were comparable to that achieved by previous studies using gas chromatography.

Continuous indirect calorimetry--a laboratory simulation of a new method for non-invasive metabolic monitoring of patients under anaesthesia or in critical care.

A method was tested which permits continuous real time monitoring of O(2) uptake in patients attached to a breathing system. The method is an indirect calorimetry technique which uses fresh gas rotameters for control, regulation and measurement of the gas flows into the system, with continuous sampling of mixed exhaust gas. Testing of this approach was conducted using a lung gas exchange simulator, in order to determine its accuracy and precision under controlled conditions, when compared to a range of simulated O(2) uptake values. The overall mean bias (standard error) was -1.3 mL min(-1) (0.3) and the standard deviation was 6.5. The performance of the method was found to be consistent across a wide range of fresh gas flow rates and O(2) concentrations from 30 to 80%. The method warrants in vivo testing under clinical conditions.

Physiologically precise simulation of multiple lung gas exchange during anaesthesia by simultaneous gas infusion and extraction.

UNLABELLED: A lung gas exchange simulator was tested which produces simultaneous uptake and/or elimination of multiple gases by an artificial test lung with physiologically realistic gas expired and exhaust gas flows, using a combination of infusion of diluting/enriching gases into the lung with lung gas extraction. A deterministic algorithm is incorporated which calculates required gas infusion and extraction flow rates for any set of possible target gas exchange values with any given set of fresh gas flows and concentrations. Six different scenarios were simulated, comprising a range of gas exchange values for each gas species which lie within a physiologically realistic range for anaesthetized patients. For each of these experiments the system was tested for 15 consecutive measurements over 25 min by measurement of gas exchange in the system using the Haldane transformation. RESULTS: the mean bias and standard error of the mean bias (SE, in parentheses) relative to the target value was: +0.001 (0.002) l min(-1) for O(2) uptake, -0.002 (0.005) l min(-1) for CO(2) production, -0.001 (0.002) l min(-1) for uptake of nitrous oxide and +0.3 (0.1) ml min(-1) for uptake of a volatile anaesthetic agent (isoflurane). The confidence limits of the mean bias were within 5% of the target value for all gases and scenarios with the exception of those where a low uptake of anaesthetic gas was specified. The confidence limits of the mean bias for the lower uptakes of isoflurane were within 10% of the target value for these scenarios and within 15% for the low uptake of N(2)O. Good accuracy and precision of this approach to lung gas exchange simulation were demonstrated, resulting in a versatile simulator.

Non-invasive measurement of intrapulmonary shunt during inert gas rebreathing.

We tested the agreement between non-invasive measurement of intrapulmonary shunt, using oxygen uptake and pulmonary capillary blood flow measurement obtained by nitrous oxide rebreathing, with that measured using mixed venous blood sampling. Nine patients were recruited pre- and post-cardiac surgery resulting in 20 sets of measurements overall. Mean shunt fraction was 12.5%, and bias between methods (+/-95% confidence limits) was -0.7% (+/-0.8%). The standard deviation of the difference was 1.7% with limits of agreement between the two methods of +2.6% and -3.9%. Correlation coefficient r was 0.90. Agreement with the invasive standard was less accurate and precise where cardiac output was measured by bolus thermodilution (mean bias +1.6%, standard deviation of the difference 2.2%, limits of agreement between the two methods of +5.8% and -2.8%, r = 0.86). Good agreement was demonstrated between the non-invasive method and the invasive reference standard.

Continuous measurement of gas uptake and elimination in anesthetized patients using an extractable marker gas.

Measurement of pulmonary gas uptake and elimination is often performed, using nitrogen as marker gas to measure gas flow, by applying the Haldane transformation. Because of the inability to measure nitrogen with conventional equipment, measurement is difficult during inhalational anesthesia. A new method is described, which is compatible with any inspired gas mixture, in which fresh gas and exhaust gas flows are measured using carbon dioxide as an extractable marker gas. A system was tested in eight patients undergoing colonic surgery for automated measurement of uptake of oxygen, nitrous oxide, isoflurane, and elimination of carbon dioxide with this method. Its accuracy and precision were compared with simultaneous measurements made with the Haldane transformation and corrected for predicted nitrogen excretion by the lungs. Good agreement was obtained for measurement of uptake or elimination of all gases studied. Mean bias was -0.003 l/min for both oxygen and nitrous oxide uptake, -0.0002 l/min for isoflurane uptake, and 0.003 l/min for carbon dioxide elimination. Limits of agreement lay within 30% of the mean uptake rate for nitrous oxide, within 15% for oxygen, within 10% for isoflurane, and within 5% for carbon dioxide. The extractable marker gas method allows accurate and continuous measurement of gas uptake and elimination in an anesthetic breathing system with any inspired gas mixture.

A new method for measurement of gas exchange during anaesthesia using an extractable marker gas.

A new method for the measurement of pulmonary gas exchange during inhalational anaesthesia is described which measures fresh gas and exhaust gas flows using carbon dioxide as an extractable marker gas. The theoretical precision of the method was compared by Monte Carlo modelling with other approaches which use marker gas dilution. A system was constructed for automated measurement of uptake of oxygen, nitrous oxide, volatile anaesthetic agent and elimination of carbon dioxide by an anaesthetized patient. The accuracy and precision of the method was tested in vitro on a lung gas exchange simulator, by comparison with simultaneous measurements made using nitrogen as marker gas and the Haldane transformation. Good agreement was obtained for measurement of simulated uptake or elimination of all gases studied over a physiologically realistic range of values. Mean bias for oxygen and nitrous oxide uptake was 0.003 l min(-1), for isoflurane 0.0001 l min(-1) and for carbon dioxide 0.001 l min(-1). Limits of agreement lay within 10% of the mean uptake rate for nitrous oxide, within 5% for oxygen and isoflurane and within 1% for carbon dioxide. The extractable marker gas method allows accurate and continuous measurement of gas exchange in an anaesthetic breathing system with any inspired gas mixture.

Noninvasive measurement of intrapulmonary shunting.

OBJECTIVE: To investigate the accuracy and precision of a noninvasive approach to measurement of pulmonary shunt fraction using simultaneous application of 2 fundamental respiratory mixing equations: the direct Fick equation for oxygen and the shunt equation of Berggren. This can be performed without mixed venous blood sampling and requires measurement of oxygen uptake and pulmonary blood flow. DESIGN: Comparison with invasive shunt fraction measured using mixed venous blood sampling and with estimated shunt fraction using an assumed arteriovenous O(2) content difference. SETTING: Major teaching hospital. PARTICIPANTS: Nine patients undergoing anesthesia for cardiac surgery. INTERVENTIONS: Pulmonary blood flow was measured using an indirect Fick technique (nitrous oxide throughflow) and by bolus thermodilution for comparison. MEASUREMENTS AND MAIN RESULTS: The mean shunt fraction measured by the invasive method was 0.145 (range 0.057-0.263). When pulmonary blood flow was measured using an indirect Fick technique (nitrous oxide throughflow), the absolute mean bias for noninvasive shunt fraction was -0.005 with a standard deviation of 0.012. Correlation was excellent (r(2) = 0.95, p < 0.001). Agreement was less precise when pulmonary blood flow was measured using thermodilution (mean bias + 0.001 with a standard deviation of 0.018). CONCLUSIONS: The noninvasive method is an accurate substitute for invasive shunt fraction measurement with mixed venous blood sampling.

Continuous measurement of cardiac output by inert gas throughflow: comparison with thermodilution.

OBJECTIVE: The throughflow method is a new technique for continuous and minimally invasive measurement of cardiac output by the Fick principle, which uses ventilation of the 2 lungs with unequal inspired gas concentrations by means of a double-lumen endobronchial tube. It exploits steady-state gas exchange and thus permits rapid repetition of measurement. DESIGN: Comparison of paired measurements by the throughflow method using N(2)O exchange with bolus thermodilution. SETTING: Departments of anesthesiology in 2 university teaching hospitals. PARTICIPANTS: Nine patients undergoing cardiac surgery in the precardiopulmonary bypass period. INTERVENTIONS: Patients intubated with a double-lumen endobronchial tube were ventilated with 45% nitrous oxide (N(2)O) to the left lung (zero to the right lung). Arterial blood gas samples were taken to measure alveolar deadspace to allow correction for the alveolar-arterial N(2)O difference and to correct for the presence of unmeasured shunt perfusion. MEASUREMENTS AND MAIN RESULTS: Throughflow measurements correlated with thermodilution (r = 0.719, p < 0.05) with a mean bias of -0.208 L/min (-5.2%). The standard error of the bias was 0.060 L/min, with 95% confidence limits for the bias of -0.088 L/min and -0.328 L/min. The limits of agreement between the 2 methods were +0.960 L/min and -1.376 L/min. CONCLUSIONS: The throughflow method showed good agreement with thermodilution. It permits continuous cardiac output measurement without the need for sampling of mixed venous blood, using techniques of lung isolation, which are readily available in clinical anesthetic practice.