Influence of pulmonary factors on pulse oximeter saturation in preterm infants.

AIM: To describe how the stability of oxygen saturation measured by pulse oximetry (SpO2%) varies within and between infants with bronchopulmonary dysplasia (BPD). METHODS: Clinically stable infants with BPD had SpO2 measured at different inspired oxygen concentrations (FIO2 expressed as %). A computer model of gas exchange, that is, ventilation/perfusion ratio (VA/Q) and shunt, plotted the curve of SpO2 versus FIO2 best fitting these data. The slope of this curve is the change in SpO2 per % change in FIO2, hence SpO2 stability, calculated at each SpO2 from 85% to 95%. RESULTS: Data from 16 infants with BPD previously described were analysed. The dominant gas exchange impairment was low VA/Q (median 0.35, IQR, 0.16-0.4, normal 0.86). Median shunt was 1% (IQR, 0-10.5; normal <2%). Slope varied markedly between infants, but above 95% SpO2 was always <1.5. In infants with least severe BPD (VA/Q ≈0.4, shunt ≤2%) median slope at 85% SpO2 was 5.1 (IQR, 3.7-5.5). With more severe BPD (VA/Q ≤0.3) slope was flatter throughout the SpO2 range. The highest FIO2 for 90% SpO2 was in infants with the lowest VA/Q values. CONCLUSIONS: In infants with BPD, there was large variation in the slope of the curve relating SpO2% to inspired oxygen fraction in the SpO2 range 85%-95%. Slopes were considerably steeper at lower than higher SpO2, especially in infants with least severe BPD, meaning that higher SpO2 target values are intrinsically much more stable. Steep slopes below 90% SpO2 may explain why some infants appear dependent on remarkably low oxygen flows.

Uptake of isoflurane during prolonged clinical anaesthesia.

Recent evidence has suggested that the rate of uptake of inhalational anaesthetic is constant during maintenance of anaesthesia, contrary to the predictions of multi-compartment uptake models. We measured isoflurane uptake using a totally closed anaesthetic system during up to 10 h of stable anaesthesia for maxillo-facial surgery on 12 adult patients. Liquid isoflurane was injected into the system under computer control to produce an end tidal concentration of 1.3 MAC of isoflurane. Bench tests demonstrated that the leakage from the system was less than 8 microl min(-1), confirming that the rate of injection of isoflurane into the system was a close upper bound on the patients' uptake. Anaesthetic usage for a 70 kg patient was 0.44e(-0.51t)+0.044e(-0.013t)+0.058e(-0.00098t) ml min(-1) of liquid isoflurane, where t is duration of anaesthesia in minutes. There was a continuing reduction in anaesthetic requirement even at the end of the period of study that was statistically significant. These data do not support the notion that isoflurane uptake is constant during stable maintenance of anaesthesia but is compatible with the conventional multi-compartment model of anaesthetic uptake and distribution.

Measuring the costs of inhaled anaesthetics.

The cost of inhalation anaesthesia has received considerable study and is undoubtedly reduced by the use of low fresh gas flows. However, comparison between anaesthetics of the economies achievable has only been made by computer modelling. We have computed anaesthetic usage for MAC-equivalent anaesthesia with isoflurane, desflurane, and sevoflurane in closed and open breathing systems. We have compared these data with those derived during clinical anaesthesia administered using a computer-controlled closed system that measures anaesthetic usage and inspired concentrations. The inspired concentrations allow the usage that would have occurred in an open system to be calculated. Our computed predictions lie within the 95% confidence intervals of the measured data. Using prices current in our institution, sevoflurane and desflurane would cost approximately twice as much as isoflurane in open systems but only about 50% more than isoflurane in closed systems. Thus computer predictions have been validated by patient measurements and the cost saving achieved by reducing the fresh gas flow is greater with less soluble anaesthetics.

The effect of sevoflurane on implicit memory: a double-blind, randomised study.

Forty-eight gynaecological patients were randomly allocated to three groups (target end-tidal sevoflurane concentration 1.2, 1.5 or 2%), and into subgroups for positive or neutral suggestion. Anaesthesia was induced by inhalation of sevoflurane in oxygen. When the target concentration was achieved, the bispectral index, computed from a bi-frontal electroencephalogram, was noted. One of two eight-word lists was then played to prime implicit memory, followed by a positive or neutral suggestion. After surgery, each patient tried to identify 24 words obscured by background noise. Priming increased the likelihood of identifying words in the 1.2% group only, i.e. there was evidence of implicit memory in this group. There was no evidence of a therapeutic effect of positive suggestion (p = 0.3), but the power of this part of the study was low. The bispectral index did not achieve statistical significance as an indicator of susceptibility to priming.

A comparison of anaesthetic tensions in arterial blood and oxygenator exhaust gas during cardiopulmonary bypass.

This study evaluates the usefulness of the analysis of gas sampled from the exhaust port of a membrane oxygenator in the estimation of anaesthetic tension in arterial blood. Sixty-seven arterial blood samples were drawn from patients undergoing hypothermic cardiopulmonary bypass with anaesthesia maintained by either isoflurane or desflurane. Anaesthetic tensions in the oxygenator exhaust gas were measured using an infrared analyser and in arterial blood using a two-stage headspace technique with a gas chromatograph. Both measurement systems were calibrated with the same standard gas mixtures. There was no difference in anaesthetic tension measured in arterial blood and gas leaving the oxygenator exhaust (isoflurane: n = 29, range: 0.3-0.8%, 95% limits of agreement: -0.08% to 0.09%; desflurane: n = 38, range: 1.5-5.4%; 95% limits of agreement -0.65% to 0.58%). We conclude that anaesthetic tensions in arterial blood can be accurately monitored by analysis of the gas emerging from the exhaust port of a membrane oxygenator.

Arterial to inspired partial pressure ratio of halothane, isoflurane, sevoflurane and desflurane in rats.

The inspired partial pressure of an anaesthetic is often used as an index of arterial partial pressure in small animal experiments. We have investigated the influence of anaesthetic solubility on the ratio of arterial to inspired partial pressure in 24 rats, allocated randomly to receive halothane, isoflurane or desflurane at four different inspired concentrations. The arterial partial pressure of the volatile agent was measured by two-stage headspace analysis using a gas chromatograph calibrated with the same gas used to calibrate the Datex Capnomac that measured the inspired concentration. Mean values of arterial to inspired ratio at the lowest concentrations were 0.60 (95% confidence intervals 0.50, 0.71) for 0.8% halothane, 0.54 (0.38, 0.69) for 0.8% isoflurane, 0.72 (0.59, 0.86) for 1.5% sevoflurane and 0.71 (0.54, 0.87) for 4% desflurane. Analysis of variance showed a significant effect of anaesthetic agent (P = 0.008) on the arterial to inspired ratio. Thus volatile anaesthetic agents do not demonstrate a fixed arterial to inspired ratio in rats.

Nitrous oxide and carbon dioxide have no effect on the blood-gas solubilities of sevoflurane and isoflurane.

UNLABELLED: Nitrous oxide (N2O) has been shown to decrease the solubility (lambdaB:G) of volatile anesthetics in human blood and, consequently, affect their rate of uptake. If this is true, then carbon dioxide (CO2) may also have an effect, which is important because methods that measure the tension of volatile anesthetics in blood washout CO2 in the process. Blood samples were obtained from fasted, healthy volunteers and patients undergoing major surgery. Each sample was divided into two aliquots: one was equilibrated at 37 degrees C in a closed glass tonometer with a mixture of isoflurane 1% and sevoflurane 2% in a test gas mixture of either 50:50 N2O/O2 or 5:95 CO2/O2; the other aliquot was equilibrated with isoflurane and sevoflurane in O2 alone as a control. Using a two-stage headspace technique using gas chromatography, we measured the lambdaB:G of isoflurane and sevoflurane in the presence and absence of the test gas in each subject. There was no significant difference between the lambdaB:G of sevoflurane and isoflurane obtained from the N2O group and their controls or between the CO2 group and their controls. We conclude that neither N2O nor CO2 has an effect on the lambdaB:G of sevoflurane or isoflurane in the concentrations tested. IMPLICATIONS: The blood solubilities of sevoflurane and isoflurane were measured with and without nitrous oxide and carbon dioxide. No differences were found. Nitrous oxide does not affect the kinetics of other anesthetics by altering their solubility. Carbon dioxide tensions need not be controlled when measuring anesthetic tensions in blood.

The uptake of sevoflurane during anaesthesia.

The rate of uptake of sevoflurane during clinical anaesthesia (1.3 MAC) was measured by computer-controlled injection of liquid anaesthetic into a closed breathing system. The cumulative uptake of sevoflurane was 4.8 ml, 7.4 ml, 9.5 ml and 11.5 ml at 30, 60, 90 and 120 min, respectively. The ratio of inspired to end-expired sevoflurane was greater than similar measurements we have made for desflurane in the past, but the absolute rate of sevoflurane uptake was less than the rate of uptake of desflurane in these cases. The rate of uptake was equivalent to 059e-0.32t + 0.039e-0.036t + 0.105e-0.0034t ml.min-1 liquid sevoflurane. Plasma urea and creatinine measured on the first postoperative day were not significantly different from pre-operative values.

Effects of a low concentration of isoflurane on contrast sensitivity in volunteers.

The effects of 0.15% quasi steady-state end-tidal isoflurane on the contrast sensitivity of five healthy volunteers were investigated by measuring their performance in computer generated letter discrimination tasks. A series of letters were displayed on a computer screen so that the luminance of the letter differed from that of the background. Two protocols were used: in the static protocol, the letter remained displayed on the screen until the subject responded, whereas in the dynamic protocol, the letter was displayed for 1/72 s only. Isoflurane significantly decreased contrast sensitivity in both protocols in all subjects.

Bispectral index: comparison of two montages.

We have compared fronto-central and bifrontal montages using a new EEG monitor, the Aspect A-1000. The monitor uses bispectral analysis to derive an index of anaesthetic depth, the bispectral index (BIS). We compared reliability, impedance and BIS for each montage. ECG electrodes placed in a bifrontal montage were more reliable than silver dome electrodes in a fronto-central montage and both types of electrodes had impedances in the clinically useful range. However, BIS values derived from each montage were found to differ in an unpredictable manner. The bifrontal montage is easy to apply and reliable but it is not comparable with a fronto-central montage. We conclude that the BIS may be useful for following trends in anaesthetic depth in individual cases but it is less helpful when making comparison between patients or as a single value.

The effect of sevoflurane on spontaneous sympathetic activity, A delta and C somatosympathetic reflexes, and associated hemodynamic changes in dogs.

UNLABELLED: This study examined the effect of sevoflurane on spontaneous renal sympathetic nerve activity (RSNA), A delta- and C-fiber-mediated somatosympathetic reflexes, and hemodynamic changes in anesthetized dogs. RSNA, and A delta and C reflexes evoked by electrical stimulation of the radial nerve were observed in multifiber recordings of efferent activity in renal sympathetic nerves. Sevoflurane was administered at 1%, 2%, 3%, and 4% end-tidal concentrations for periods of 20 min. The mean A delta reflexes decreased by 20%, 39%, and 54% (P < 0.05 to < 0.01), and the C reflexes decreased by 38%, 62%, and 74% (P < 0.05 to < 0.01) at concentrations of 2%, 3%, and 4%, respectively. The relatively greater effect on C reflexes was significant (P < 0.05) and comparable with the effect of mu-opioids. There was no change in mean RSNA, heart rate (HR), and cardiac output (CO) up to 3% sevoflurane, but these decreased by 36%, 24%, and 13% (P < 0.05), respectively, at 4% sevoflurane. Sevoflurane 1%-4% caused a virtually linear reduction in systemic vascular resistance (SVR) from 7% (P < 0.05) to 44% (P < 0.05), together with a reduction in mean arterial pressure (MAP) that was significant for concentrations greater than 2%. The results indicate that sevoflurane causes a greater depression of C compared with A delta reflexes, and that the reduction in MAP was entirely due to a decrease in SVR up to 3%, whereas at 4% sevoflurane, reductions in sympathetic activity, HR, and CO also contributed its depressor effect. IMPLICATIONS: The relatively greater depressant effect of sevoflurane on C compared with A delta nociceptive somatosympathetic reflexes is similar to mu-opioids. The hypotensive effect of sevoflurane was significant at 2% concentration, whereas heart rate, cardiac output and sympathetic activity were reduced only at concentrations greater than 3%.

Effect of temperature on the solubility of desflurane, sevoflurane, enflurane and halothane in blood.

We have investigated the effect of temperature on the blood-gas solubility of desflurane, sevoflurane, enflurane and halothane. Blood was equilibrated with gas mixtures of known composition in open cuvette or closed flask tonometers over a temperature range of 29-39 degrees C, and the concentration of each anaesthetic in blood was measured at 37 degrees C by repeated headspace analysis using a gas chromatograph. Solubility increased by 5.4% of the solubility at 37 degrees C for each degree that equilibration temperature was reduced. This result was true for all anaesthetics in all blood samples, and is in keeping with results for other volatile anaesthetics.

The loss of sevoflurane from a closed breathing system.

When volatile anaesthetics are used in a closed breathing system it is usually assumed that inflow of anaesthetic to the system matches uptake by the patient. Early laboratory reports on the interactions between sevoflurane and soda lime cast doubt on that assumption. We have measured the loss of sevoflurane, desflurane and isoflurane from a closed breathing system and found no differences of consequences.

A new method for measurement of anaesthetic partial pressure in blood.

We have developed a simple, reliable method for rapid analysis of the partial pressure of volatile anaesthetic agents, based on a two-stage, head-space analysis. It is designed to solve the problems associated with reduced solubility of modern anaesthetics. After equilibration and analysis of a 2-ml sample of blood at 37 degrees C, 1 ml is transferred to another vial for a second equilibration. This ensures that there is no vapour in the headspace before the second equilibration. Measurements were performed on human blood samples equilibrated with 1% sevoflurane, 2.5% isoflurane or 3% desflurane in a tonometer. The mean error in the sample measurements was -2.3% of the tonometer reading and the 95% confidence interval for an individual measurement was +/- 8.5%. Blood samples may be stored overnight without any significant change in the results.

An alternative method of nitrous oxide delivery into a minimal-flow circle breathing system.

We have sought to define a way in which nitrous oxide can be safely and universally used at minimal to low flows by utilising a circle system with a controlled leak provided by a standard gas analyser sampling line and a fresh gas supply of 50% nitrous oxide in oxygen, entering from a trunk interposed between the ventilator and the circle system. Although preliminary calculations suggested that this arrangement was likely to work, it was found that 13 of 23 patients studied prospectively developed an inspired oxygen fraction below 0.3. We conclude that, although this arrangement provides a new means of introducing nitrous oxide into the circle breathing system, it does not appear inherently safer or more convenient than the conventional route.

Magnetic resonance spectroscopy of isoflurane kinetics in humans. Part I: Elimination from the head.

We describe the first human experiments to demonstrate wash-out of isoflurane using fluorine magnetic resonance spectroscopy. Using a surface receive coil, we found two-compartment kinetics within the head with decay half-times of 9.5 and 130 min, but the signal was too weak to localize the compartments. If the fast compartment is assumed to be the brain then our results match the predictions of the classical perfusion-limited pharmacokinetic model of inhalation anaesthesia.

Magnetic resonance spectroscopy of isoflurane kinetics in humans. Part II: Functional localization.

We describe the first experiments to relate the cerebral kinetics of isoflurane (determined by fluorine magnetic resonance spectroscopy) to cerebral function. Using a surface receive coil we found two-compartment kinetics within the head with equilibrium half-times of 3.5 min and approximately 1 h with respect to expired isoflurane concentrations. Using critical fusion flicker frequency as an objective measure of the cerebral effect of isoflurane, we found evidence to identify the fast component as the brain. Responsiveness to command was lost at a brain partial pressure of 0.3% isoflurane. We conclude that the measured cerebral kinetics of isoflurane exactly matched the predictions of the classical perfusion-limited model.

The estimation of inspired desflurane concentration in a low-flow system.

We have examined the predictability of inspired desflurane concentration during low-flow anaesthesia using a to-and-fro breathing system. Twenty-two adult patients requiring mechanical ventilation of the lungs during surgery took part in the study. Using a fresh gas flow of 1 l.min-1, the ratio of inspired desflurane concentration to desflurane vaporizer setting was found to be approximately 0.75 after 9 min of anaesthesia and at 2 l.min-1 fresh gas flow the ratio was approximately 0.9 after 2 min of anaesthesia. These ratios were maintained throughout the procedure, except for a few minutes following each change in vaporizer setting.