Effects of midazolam and nitrous oxide on the minimum anesthetic concentration of isoflurane in the ball python (Python regius).

OBJECTIVE: To evaluate the effects of midazolam and nitrous oxide (N2O) on the minimum anesthetic concentration of isoflurane (MACISO) in ball pythons. STUDY DESIGN: Prospective, crossover, randomized, semi-blinded study. ANIMALS: A total of nine healthy adult female ball pythons (Python regius) weighing 2.76 ± 0.73 kg. METHODS: In each snake, three protocols were evaluated with 2 week washouts: treatment MID-O2, midazolam (1 mg kg-1) administered intramuscularly (IM) and anesthesia induced with isoflurane-oxygen; treatment SAL-O2, saline (0.2 mL kg-1) IM and anesthesia with isoflurane-oxygen; and treatment SAL-N2O, saline IM and anesthesia with isoflurane and 50% nitrous oxide (N2O):50% oxygen. In each treatment, isoflurane was administered by face mask immediately after premedication. Snakes were endotracheally intubated and inspired and end-tidal isoflurane concentrations were monitored. The study design followed a standard bracketing technique, and the MACISO was determined using logistic regression. Electrical stimulation using a Grass stimulator connected to the base of the tail (50 V, 50 Hz, 6.5 ms pulse-1) was used as the supramaximal stimulus. Blood-gas analysis was performed on cardiac blood collected immediately following intubation and after the last stimulation. Blood-gas variables were compared over time and between treatments using linear mixed models. RESULTS: MACISO at a body temperature of 30.1 ± 0.4 °C was 1.11% (95% confidence interval, 0.94-1.28%) in SAL-O2 and was significantly decreased to 0.48% (0.29-0.67%) in MID-O2 (p < 0.001) and to 0.92% (0.74-1.09%) in SAL-N2O (p = 0.016). PO2 was significantly lower in MID-O2 and SAL-N2O than in SAL-O2. CONCLUSIONS AND CLINICAL RELEVANCE: Midazolam significantly decreased the MACISO by 57% in ball pythons, whereas addition of N2O resulted in a modest, although significant, decrease (17%). MACISO in ball pythons was lower than those previously reported in reptiles.

Effects of carbon source, C/N ratio, nitrate, temperature, and pH on N2O emission and functional denitrifying genes during heterotrophic denitrification.

The effects of operational parameters such as carbon source, C/N ratio, initial nitrate concentration, temperature, and pH value on heterotrophic denitrification and functional denitrifying genes were evaluated. When methanol was used as the sole carbon source, complete denitrification was performed in a short time without nitrous oxide (N2O) emission. Complete denitrification was performed at high C/N ratios (5.14 and 12.85) and low initial nitrate concentrations (75.9 and 151.6 mg N L-1). The denitrification rate was not temperature-sensitive in the range of 25-35 °C, but tended to decrease at a low pH of 5-6. The relationships between N2O emission and functional genes under various operational conditions were investigated by Pearson correlation and association network analyses. The C/N ratio was a key factor for N2O emission during the heterotrophic denitrification process. This information on the denitrification performance and its association with functional gene dynamics under various operational conditions is useful for N2O mitigation strategies for wastewater treatment processes.

Immobilization of Azospira sp. strain I13 by gel entrapment for mitigation of N2O from biological wastewater treatment plants: Biokinetic characterization and modeling.

Development of a strategy to mitigate nitrous oxide (N2O) emitted from biological sources is important in the nexus of wastewater treatment and greenhouse gas emission. To this end, immobilization of N2O-reducing bacteria as a biofilm has the potential to ameliorate oxygen (O2) inhibition of the metabolic activity of the bacteria. We demonstrated the effectiveness of calcium alginate gel entrapment of the nosZ clade II type N2O-reducing bacterium, Azospira sp. strain I13, in reducing levels of N2O, irrespective of the presence of O2. Azospira sp. strain I13 cells in the gel exhibited N2O reduction up to a maximum dissolved oxygen concentration of 100 µM in the bulk liquid. The maximum apparent N2O uptake rate, [Formula: see text] , by gel immobilization did not appreciably decrease, retaining 72% of the N2O reduction rate of the cell suspension of Azospira sp. strain I13. Whereas gel immobilization increased the apparent half-saturation constant for N2O, [Formula: see text] , and the apparent O2 inhibition constant, [Formula: see text] , representing the degree of O2 resistance, correspondingly increased. A mechanistic model introducing diffusion and the reactions of N2O consumption was used to describe the experimental observations. Incorporating Thieles modulus into the model determined an appropriate gel size to achieve N2O reduction even under aerobic conditions.

The interaction of nitrous oxide and fentanyl on the minimum alveolar concentration of sevoflurane blocking motor movement (MACNM) in dogs.

The study objective was to determine the effects of 70% nitrous oxide (N2O) and fentanyl on the end-tidal concentration of sevoflurane necessary to prevent movement (MACNM) in response to noxious stimulation in dogs. Six healthy, adult, intact male, mixed-breed dogs were used on 3 occasions in a randomized crossover design. After induction of anesthesia with sevoflurane, each of the following treatments was randomly administered: fentanyl loading dose (Ld) of 15 µg/kg and infusion of 6 µg/kg per hour [treatment 1 (T1)], 70% N2O (T2), or fentanyl (Ld of 15 µg/kg and infusion of 6 µg/kg per hour) combined with 70% N2O (T3). Each dog received each of the 3 treatments once during the 3-week period. Determination of MACNM was initiated 90 min after the start of each treatment. The values were compared using the baseline MACNM, which had been determined in a previous study on the same group of dogs. Data were analyzed using a mixed-model analysis of variance (ANOVA) and Tukey-Kramer tests, and expressed as least squares mean ± SEM. The baseline MACNM decreased by 36.6 ± 4.0%, 15.0 ± 4.0%, and 46.0 ± 4.0% for T1, T2, and T3, respectively (P < 0.05), and differed (P < 0.05) among treatments. Mean fentanyl plasma concentrations did not differ (P ≥ 0.05) between T1 (3.70 ± 0.56 ng/mL) and T3 (3.50 ± 0.56 ng/mL). The combination of fentanyl and N2O resulted in a greater sevoflurane MACNM sparing effect than either treatment alone.

L'objectif de la présente étude était de déterminer les effets de l'oxyde nitreux (N2O) à 70 % et du fentanyl sur la concentration de sevoflurane en fin d'expiration nécessaire pour empêcher le mouvement (MACNM) en réponse à une stimulation désagréable chez des chiens. Six chiens mâles intacts adultes en santé de race croisée furent utilisés en 3 occasions dans des études croisées aléatoires. Après induction de l'anesthésie avec du sevoflurane, chacun des traitements suivants fut administré de manière aléatoire : dose d'induction de fentanyl (Ld) de 15 µg/kg et infusion de 6 µg/kg par heure [traitement 1 (T1)], 70 % N2O (T2), ou fentalyl (Ld de 15 µg/kg et infusion de 6 µg/kg par heure) combiné avec 70 % N2O (T3). Chaque chien a reçu chacun des trois traitements une fois durant la période d'essai de 3 semaines. La détermination du MACNM fut débutée 90 min après le début de chaque traitement. Les valeurs furent comparées en utilisant la valeur de base de MACNM, qui avait été déterminée dans une étude antérieure avec le même groupe de chiens. Les données furent analysées en utilisant un modèle mixte d'analyse de variance (ANOVA) et un test de Tukey-Kramer, et présentées comme la moyenne des moindres carrés ± écart-type. La valeur de base de MACNM diminua de 36,6 ± 4,0 %, 15,0 ± 4,0 %, et 46,0 ± 4,0 % respectivement pour T1, T2 et T3 (P < 0,05), et différait (P < 0,05) entre les traitements. Les concentrations plasmatiques moyennes ne différaient pas (P ≥ 0,05) entre T1 (3,70 ± 0,56 ng/mL) et T3 (3,50 ± 0,56 ng/mL). La combinaison de fentanyl et de N2O a produit un plus grand effet réducteur sur le MACNM de sevoflurane que chaque traitement individuel.(Traduit par Docteur Serge Messier).

Clinical applications of arterial spin labeling.

MR arterial spin labeling is primarily applied as a neuroimaging method to measure cerebral blood flow. As this technique becomes more widely available, a basic understanding of the clinical applications is necessary for optimal utilization in the setting of patient care. This review focuses on the use of arterial spin labeling imaging for the evaluation of cerebrovascular disease, brain tumors and neuropsychiatric illness.

The Kety-Schmidt technique for quantitative perfusion and oxygen metabolism measurements in the MR imaging environment.

SUMMARY: The Kety-Schmidt technique provides quantitative measurement of whole-brain CBF. CBF is measured as the area between the arterial and venous washout curves of a diffusible tracer. Oxygen extraction and metabolism may be calculated from arterial and venous samples. In this report, we present a method for performing these measurements in an MR imaging environment. This technique could be useful for validation of MR imaging methods of hemodynamic and metabolic measurements in humans.

A randomized comparison of nitrous oxide versus intravenous ketamine for laceration repair in children.

OBJECTIVE: Ketamine is used intramuscularly or intravenously as a sedative when repairing the skin lacerations of children in many emergency departments (EDs). Nitrous oxide (N(2)O) has the advantages of being a sedative agent that does not require a painful injection and that offers shallower levels of sedation and a rapid recovery of mental state. We evaluated the clinical usefulness of N(2)O compared with intravenous ketamine when used for the repair of lacerations in children in the ED. METHODS: From January to December 2009, we performed a prospective, randomized study at a single academic ED enrolling pediatric patients aged 3 to 10 years who needed primary repair of a laceration wound. The primary outcome was recovery time, which was defined as the time from completion of procedure to recovery of mental state. Other outcomes were sedation depth, pain scale, adverse effects, and satisfaction with sedation. RESULTS: There were 32 children who were randomly assigned. Recovery times were shorter in the N(2)O group compared with those in the ketamine group (median [interquartile range (IQR)], 0.0 minutes, [0.0-4.0 minutes] vs 21.5 minutes [12.5-37.5 minutes], P < 0.05). Sedation levels were deeper in the ketamine group than in the N2O group, but pain scales were comparable between groups. No difference was observed in the satisfaction scores by physicians, parents, or nurses. CONCLUSIONS: Nitrous oxide inhalation was preferable to injectable ketamine for pediatric patients because it is safe, allows for a faster recovery, maintains sufficient sedation time, and does not induce unnecessarily deep sedation.

Direct measurement of nitrous oxide kinetics.

BACKGROUND: Using conscious subjects, measurement of the effects of low concentrations of anaesthetic agents can allow the dynamics of onset and offset of the agent to be measured and kinetic values estimated. However, the tests have to be rapid and preferably assess cerebral function. METHODS: We used a short version of the digit symbol substitution test (DSST) that allowed frequent measurement of the impairment caused by nitrous oxide. We compared 10 min of onset and offset of breathing 5% and 30% nitrous oxide in 30% oxygen, compared with 30% oxygen only. End-tidal nitrous oxide concentrations were used to predict the concentration in a central compartment, according to a range of T(1/2) values chosen to be consistent with possible cerebral blood flow values. RESULTS: We studied 19 volunteers and estimated a mean response. Only 30% nitrous oxide decreased the DSST. When DSST scores were related to the values in the predicted central compartment, the best dose-effect relationship was found when the T(1/2) was 37 s, consistent with a regional blood flow of about 120 ml 100 g(-1) min(-1). CONCLUSIONS: The onset of nitrous oxide effect on DSST is rapid, consistent with the perfusion of metabolically active cerebral cortical tissues. The rate of onset is greater than previous measures based on a motor test which involved the function of subcortical structures in the central nervous system.

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.

Xenon as an anesthetic agent.

Discovered in 1898 by British chemists, xenon is a rare gas belonging to the noble gases of the periodic table. Xenon is used in many different ways, from high-intensity lamps to jet propellant, and in 1939, its anesthetic properties were discovered. Xenon exerts its anesthetic properties, in part, through the noncompetitive inhibition of N-methyl-D-aspartate receptors. Currently, xenon is being used primarily throughout Europe; however, the high price of manufacturing and scavenging the noble gas has discouraged more widespread use. As technology in anesthetic delivery improves, xenon is being investigated further as a possible replacement for nitrous oxide as an inhalational agent. This article reviews the anesthetic properties of xenon and current and potential research about the gas.

Low-flow anaesthesia at a fixed flow rate.

AIMS AND OBJECTIVES: This study attempts to assess the safety of low-flow anaesthesia (LFA) at fixed flow rates with particular reference to the incidence of a decline in FiO(2) below safe levels of 0.3 and to determine whether LFA can be used safely in the absence of an FiO(2) monitor. METHODS: A total of 100 patients undergoing procedures under general anaesthesia at fresh gas flows of 300 ml/min of O(2) and 300 ml/min of N(2)O were monitored while maintaining the dial setting of isoflurane at 1.5% for 2 h. The changes in gas composition were analysed and even a single recording of FiO(2) of <0.3 was considered sufficient to render the technique unsafe in the absence of gas monitors. RESULTS: The lowest recorded value of FiO(2) was 31% (v/v%). There was no incidence of adverse events necessitating the conversion from low flows to conventional flows. CONCLUSIONS: We conclude that low flows of 300 ml/min of N(2)O and 300 ml/min of oxygen can be used safely for a period of 2 h without the use of monitors for gas analysis of oxygen and agent in adult patients weighing between 40 and 75 kgs.

Closed-form solutions for the optimum equivalence of first-order compartmental models and their implications for classical models of closed-circuit anesthesia.

Given a function that describes the uptake of a substance into the body with time, an analytical technique is described which transforms that function into a model of parallel first-order compartments that converges to the same uptake profile as the number of compartments is increased. The fitting of the compartmental model to the given uptake function is optimized to minimize the squared error. A necessary condition of the analytical method is that the uptake function be capable of being successively integrated at least as many times as the number of desired compartments. The uptake function should also be monotonically decreasing as all parallel first-order compartment models predict monotonically decreasing uptake. We applied this technique and ascertained the compartmental structure of the Severinghaus relationship, a longstanding observation in the field of clinical anesthesia that the uptake of nitrous oxide follows an inverse-square-root of time profile. The Severinghaus relationship is numerically poorly behaved at a time of zero elapsed minutes, predicting an instantaneously infinite uptake. Nevertheless, modeling of the first minute of anesthesia is necessary for characterizing the initial induction of anesthesia and methods of maintaining closed-circuit anesthesia such as the unit dose method. Using solely analytical methods, solutions for the compartmental properties of a mammillary model that matches the Severinghaus relationship for any expressed time interval are produced. These properties are compared to currently accepted values for the uptake of nitrous oxide. When matched to the Severinghaus relationship in the range of 0-100 min with a three-compartment model, we identified time constants of 0.28, 4.69 and 33.49 min with associated apparent volumes of 1.44, 2.14 and 7.97 l, respectively. The time constants in particular contrast to our earlier findings for the range of 1-100 min (1.46, 7.41 and 42.0 min). Our earlier findings were well matched to published time constants for tissues in classical pharmacokinetic models for volatile uptake. Consequently, we conclude that rigid adherence to the Severinghaus relationship from a time of zero minutes may lead to the over-administration of anesthetic agent due to an implicit mischaracterization of the relevant compartmental properties.

Cerebral blood flow and oxygen metabolism measured with the Kety-Schmidt method using nitrous oxide.

BACKGROUND: The Kety-Schmidt method is the reference method for measuring global cerebral blood flow (CBF), cerebral metabolic rates (CMR) and flux, especially where scanners are unavailable or impractical. Our primary objective was to assess the repeatability of the Kety-Schmidt method in a variety of different approaches using inhaled nitrous oxide (N2O) as the tracer, combined with photoacoustic spectrometry. A secondary objective was to assess the impact of this tracer on the systemic vascular concentration of nitrite (NO2(-)). METHODS: Twenty-nine healthy male volunteers underwent 61 CBF measurements by breathing a normoxic gas mixture containing 5% N2O until tension equilibrium. Paired blood samples were collected from an arterial and a jugular bulb catheter in the saturation or desaturation phase, by continuous or the discontinuous sampling. N2O concentration was measured with photoacoustic spectrometry after equilibration of blood samples with air. CBF was calculated by the Kety-Schmidt equation. CMR of oxygen (CMRO2) was determined by the Fick principle. NO2(-) in plasma and red blood cells (RBC) was measured by ozone-based chemiluminescence. RESULTS: The most robust approach for CBF measurement was achieved by discontinuous sampling in the desaturation phase [CBF, 64 (95% confidence interval, 59-71 ml)] 100 g/min; CMRO2 1.8 (1.7-2.0) micromol/g/min). The tracer did not influence plasma or RBC NO2(-) (P>0.05 vs. baseline). CONCLUSION: These findings confirm the reliability and robustness of the Kety-Schmidt method using inhaled N2O for the measurement of global CBF and CMR. At the low tracer concentration used, altered NO metabolism is unlikely to have affected cerebral haemodynamic function.

The Severinghaus square root of time relationship for anesthetic uptake and its implications for the stability of compartmental pharmacokinetics.

For nitrous oxide, the first anesthetic for which uptake was measured in humans, Severinghaus noted empirically that a plot of the log of uptake against the log of elapsed time produced a straight line with slope -0.5, suggesting that uptake is proportional to the inverse square root of time. This result is something of a black box model, based on empirical curve fitting without regard to physiology. Some authors (e.g., Lowe) repeatedly returned to this inverse square root of time model as a benchmark while others (e.g., Hendrickx) questioned its validity and demanded the relationship be expressed with a physiologic model whose structure matches the known physiology being modeled. Nevertheless, the fact that authors have repeatedly come back to this inverse square root of time model as a benchmark suggests that it might have some underlying validity which has not previously been recognized. We re-explored this mathematically in an attempt to reveal hitherto undiscovered insights or limitations. In this study, we examined the square root of time model (viewed as a power function) and compared it with multi-compartment models. Further, we explored the stability of this relationship to systematic variation in the power value and also to the superimposition of noise-like perturbations, seeking conditions under which it might not work. Based upon this theoretical analysis, we also speculate on the existence of a physiological compartment with a time constant between that of the vessel-rich group (VRG) and muscle, and what the identity of such a compartment might be.

The rate of alveolar-capillary uptake of sevoflurane and nitrous oxide following anaesthetic induction.

The rate of anaesthetic gas uptake from the breathing system has been extensively measured, but this does not reflect the true rate of early gas uptake by pulmonary blood, which drives inhalational induction of anaesthesia. In eight patients undergoing coronary bypass surgery, we measured the rate of alveolar-capillary uptake of anaesthetic gases up to 30 min following introduction of 0.5% sevoflurane and 33% nitrous oxide using the reverse Fick method, in which blood partial pressures were measured using a headspace equilibration technique. Simultaneous measurements of gas uptake from the breathing system were made by indirect calorimetry. Measured rates of sevoflurane and nitrous oxide uptake from the breathing system agreed well with previously described formulae when adjusted for inspired concentration. The time course of alveolar-capillary gas uptake followed a characteristic rising curve peaking at 3-4 min and then exponentially declining, and for nitrous oxide was significantly higher than previously estimated.

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.

Quantitation of the effect of nitrous oxide on rocuronium infusion requirements using closed-loop feedback control.

BACKGROUND: Nitrous oxide has a minor effect on the effective dose 50% values of bolus doses of rocuronium. The authors have studied the effect of nitrous oxide on the infusion requirements of rocuronium using closed-loop feedback control of rocuronium infusion. METHODS: The authors obtained institutional approval and informed consent to study 70 patients. The patients were given total intravenous anesthesia with propofol and remifentanil by target-controlled infusion and were randomly assigned to one of two groups, one receiving nitrous oxide with 30% oxygen (n = 35) and the other group receiving air with 30% oxygen (n = 35). The possible interaction of rocuronium with nitrous oxide was quantitated by determining the asymptotic steady state rate of infusion of rocuronium necessary to produce a constant 90% neuromuscular block. This was accomplished by applying nonlinear curve fitting to data on the cumulative dose requirement during the initial 90-min period after bolus administration of rocuronium. RESULTS: Patient characteristics and controller performance, i.e., the ability of the controller to maintain the neuromuscular block constant at the set point, did not differ significantly between the groups. The administration of nitrous oxide did not affect rocuronium infusion requirements. The mean steady state rates of infusion were 33.0 +/- 9.8 and 36.9 +/- 13.2 mg/h in the nitrous oxide-total intravenous anesthesia and air-total intravenous anesthesia groups, respectively. CONCLUSIONS: Nitrous oxide does not affect the infusion requirements of rocuronium to a clinically significant degree.

Monitoring of fluid absorption with nitrous oxide during transurethral resection of the prostate.

BACKGROUND: The fluid absorption that occurs during transurethral resection of the prostate (TURP) can be indicated and quantified by the ethanol method. Recently, nitrous oxide (N(2)O) was tested in animals and volunteers and seemed to be more accurate and safe. The present study compared these two methods in surgical patients. METHODS: Eighty-six TURPs were performed at two hospitals using an irrigating fluid that contained 3% mannitol, 1% ethanol and 0.004% N(2)O (40 ml/l). The ethanol concentration was measured by end-expiratory tests every 10 min. The N(2)O concentration was measured by a flared nasal cannula every second. Fluid absorption was calculated based on a regression equation (ethanol method) from the area under the curve based on the samples where CO(2) >median (N(2)O method). RESULTS: Thirteen patients (15%) absorbed >300 ml of fluid as indicated by the ethanol method. The median volume was 707 ml (range 367-1422). Ethanol yielded higher figures for fluid absorption up to 700-800 ml, whereafter the N(2)O method indicated that the absorption was larger. Over the entire range, the mean difference between the two methods at the end of any 10-min period of TURP was only +45 ml, although the 95% limits of agreement were quite separated (-479 to +569 ml). CONCLUSIONS: The N(2)O method does not require forced breath sampling and was successfully apply clinically. However, there was a dose-dependent difference in result between the ethanol and N(2)O methods, which markedly separated the limits of agreement for a wider range of fluid absorption events.