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.

Synergistic antinociceptive interaction between sevoflurane and intrathecal fentanyl in dogs.

This study determined the nature of the antinociceptive interaction between sevoflurane and intrathecal fentanyl on somatosympathetic reflexes in anaesthetized dogs. Afferent A delta- and C-fibre-mediated somatosympathetic reflexes, evoked by supramaximal electrical stimulation of tibial nerves, were recorded from renal sympathetic nerves. The effect of fentanyl alone, administered intrathecally (i.t.) in incremental doses from 2 to 64 micrograms, was compared with the effect of the same doses during the administration of 1.5% sevoflurane. The mean ED50s for the depressant effect of fentanyl (i.t.) on A delta and C reflexes were 35.6 micrograms and 14.2 micrograms while 1.5% sevoflurane, when administered alone, depressed them by 15.5% (P < 0.05) and 27.5% (P < 0.01) respectively. During the administration of 1.5% sevoflurane, the mean ED50s of fentanyl (i.t.) for the depression of A delta and C reflexes were reduced by 76% and 75%, to 8.5 micrograms and 3.5 micrograms respectively. The combined antinociceptive effects of sevoflurane and intrathecal fentanyl were not additive but exhibited a high degree of synergistic interaction.

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits.

BACKGROUND: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e.g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. METHODS: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 microgram.kg-1 i.v. or midazolam 0.05 mg.kg-1 i.v. on the effects of propofol and fentanyl respectively on PNA were studied. RESULTS: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg.kg-1 i.v. and 32 micrograms.kg-1 i.v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg.kg-1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg.kg-1. The mean ED50s, calculated from dose-response curves, were 5.4 mg.kg-1, 3.9 micrograms.kg-1 and 0.4 mg.kg-1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 microgram.kg-1 i.v. or midazolam 0.05 mg.kg-1 i.v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg.kg-1 and 8 micrograms.kg-1, respectively. CONCLUSION: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.

Synergism between sevoflurane and intravenous fentanyl on A delta and C somatosympathetic reflexes in dogs.

UNLABELLED: In this study, we defined the nature of the interactions between sevoflurane and fentanyl on spontaneous and reflex-evoked sympathetic activity, resting heart rate (HR), and mean arterial pressure (MAP). Spontaneous renal sympathetic nerve activity (RSNA) and A delta- and C-fiber-mediated somatosympathetic reflexes, evoked by electrical stimulation of radial nerves, and HR and MAP were recorded in anesthetized dogs. In one group, the effects of incremental doses of 2-64 micrograms/kg fentanyl i.v. were observed. It had a greater inhibitory effect on C than on A delta reflexes, which were abolished by mean cumulative doses of 64 micrograms/kg and approximately 128 micrograms/kg, respectively. Although 1.5% sevoflurane reduced C reflexes by 28% and A delta reflexes by only 12%, it reduced the total doses of fentanyl required for their abolition to 32 micrograms/kg and 64 micrograms/kg, respectively. Mean RSNA, HR, and MAP values were reduced by 46%, 54%, and 30%, respectively, by fentanyl alone and by 23%, 11%, and 17%, respectively, in response to 1.5% sevoflurane. The combination of fentanyl and sevoflurane caused reductions of 44%, 54%, and 41%, respectively, which indicates a less than additive effect. These results indicate that sevoflurane interacts synergistically with fentanyl to depress A delta and C somatosympathetic reflexes, whereas for RSNA, HR, and MAP, their effects were less than the additive. IMPLICATIONS: Although fentanyl caused a greater depression of C than of A delta reflexes to the point of abolition, the maximal depression of spontaneous sympathetic activity, heart rate, and arterial pressure occurred at smaller doses. The combined depressant effects of sevoflurane and fentanyl were synergistic on somatosympathetic reflexes but were less than additive on spontaneous sympathetic activity, heart rate, and arterial pressure.

Effect of sevoflurane on spontaneous sympathetic activity and baroreflexes in rabbits.

Sevoflurane causes a decrease in mean arterial pressure (MAP). We have studied in anaesthetized rabbits its interactive effects on MAP, the autonomic nervous system and baroreflexes. During sevoflurane administration changes in renal sympathetic nerve activity (RSNA) and heart rate (HR) were observed: (1) when the normal decrease in MAP occurred; (2) when this was prevented by angiotensin II; (3) during a similar decrease in MAP induced by infusion of sodium nitroprusside (SNP) without sevoflurane administration; and (4) during pressor and depressor responses to phenylephrine and SNP. There was a reduction in MAP from 80 to 40 mm Hg after 1-4% sevoflurane without changes in HR, while RSNA remained unchanged only up to concentrations of 3% and was depressed by 37% (P < 0.05) with 4% sevoflurane. When MAP was maintained constant with angiotensin II, both HR and RSNA decreased, by 12% and 69%, respectively, after 4% sevoflurane (P < 0.05). A decrease in MAP of 40 mm Hg during infusion of SNP increased HR and RSNA by 22% (P < 0.05) and 150% (P < 0.01), respectively. At 2% sevoflurane, baroreflex sensitivity (i.e. delta RSNA/delta MAP and delta HR/delta MAP) was depressed by 36% and 57%, respectively, for the pressor effects of pherylephrine, and by 89% and 81%, respectively, for the depressor effects of SNP. We conclude that the baroreflexes continued to compensate for the effects of sevoflurane on sympathetic and cardiomotor activity with concentrations up to 3% and 4%, respectively.

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.

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.

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.

Metabolic and hormonal responses to induced hypotension for middle ear surgery.

We have investigated in 30 patients the metabolic and hormonal responses to middle ear surgery using induced hypotension to a mean arterial pressure of 55 mm Hg. A standardized anaesthetic technique of propranolol, thiopentone-vecuronium-isoflurane was used in all patients and hypotension induced with sodium nitroprusside, trimetaphan camsylate or additional isoflurane. All patients showed a classic stress response with an increase in circulating blood glucose, cortisol and growth hormone concentrations. Blood lactate and plasma uric acid concentrations changed little during operation, suggesting that tissue oxygenation was adequate. However, the former declined after operation, possibly as a result of the concomitant use of propranolol. There were no significant differences between the three hypotensive techniques in their effects on the hormonal and metabolic response, although the increase in blood glucose concentration in the trimetaphan group was obtunded. We conclude that induced hypotension for middle ear surgery induced an endocrine and metabolic response of small magnitude and short duration.

Effects of enflurane and halothane on carbohydrate metabolism in isolated perfused rabbit lungs.

Isolated, perfused rabbit lungs were used to investigate the effects of enflurane and halothane on pulmonary carbohydrate metabolism. The development of oedema in the preparation was assessed by continuous measurement of pulmonary artery pressure, airway pressure and lung weight. Ventilation of the lungs with 2% enflurane for 3 h had no effect on the rates of glucose utilization and lactate production and there were only small changes in the indices of oedema. Likewise, ventilation with 1% halothane for 1 h had no effect on the rates of glucose utilization and lactate production, and did not change significantly the concentrations of glycogen, glucose, glycolytic intermediates and high-energy phosphate compounds in lung tissue. Enflurane and halothane, at clinically relevant concentrations, probably do not influence carbohydrate metabolism in the lung.