Blood-gas Solubility Research Articles

The safety, efficacy and recovery characteristics of desflurane versus propofol for anaesthesia in an older day surgery population

Desflurane is one of a new generation of volatile anaesthetic agents with a low blood gas solubility coefficient of 0.42 (cf. Isoflurane 1.40 and nitrous oxide 0.46) and the potential for rapid recovery and minimal post-operative hangover. This could have advantages for day surgery particularly in an older day surgical population. This study compared the maintenance of anaesthesia with desflurane or propofol in a randomised, comparative, controlled and open labelled trial. A variety of tests of or indices of recovery were studied including psychometric testing and the recovery from similar depths of anaesthesia as assessed by the coherent frequency analysis of auditory evoked potentials in the electroencephalogram (EEG).

Rapid inhalation induction in children: 8% sevoflurane compared with 5% halothane

Sevoflurane has a lower blood-gas solubility and a less pungent odour than halothane; this may allow more rapid induction of anaesthesia. In a randomized, blinded study, we compared the induction characteristics of maximum initial inspired concentration of 8% sevoflurane and 5% halothane using conventional vaporizers in children aged 3 months to 3 years. There was no statistically significant difference in induction times between the two groups: mean times to loss of consciousness were 1 min 12 s (SD 18 s, range 40 s-1 min 44 s) for sevoflurane and 1 min 16 s (SD 17 s, range 50 s-1 min 52 s) for halothane, although these times were shorter than in previous studies using a gradual increase in vapour concentration. A small number of complications were noted in both groups, although none interfered with induction of anaesthesia. Struggling scores were lower in the sevoflurane group than in the halothane group (chi-square for trends = 6.34, P < 0.02). A significant number (11 of 15) of parents of children in the sevoflurane group who had previous experience of halothane induction preferred sevoflurane (chi-square for trends = 4.03, P < 0.05). We conclude that with this technique, induction was rapid with both sevoflurane and halothane. Our assessment of patient struggling and parents' perceptions suggests that induction with sevoflurane was more pleasant than with halothane.

Seroflurane Versus Isoflurane in Single-Breath Induction

In Response: Doctors Abramson and Pivalizza raise two important points. First, we recognize that because of equipment limitations, we were unable to use equipotent inhaled concentrations of sevoflurane and isoflurane for our single-breath inductions [1]. However, sevoflurane's low blood-gas solubility and minimal pungency allowed single-breath induction to occur as quickly as it did with isoflurane, despite the use of a lower relative concentration. When a vaporizer capable of delivering 8% sevoflurane is used, anesthesia is induced even more rapidly; there is also a much lower incidence of partial awakening and crowing after redistribution of the initial inhaled dose of sevoflurane. Our second concern relates to the calculation of "minimum alveolar anesthetic concentration (MAC) equivalents" when an anesthetic is administered with N2 O. Katoh and Ikeda found that the concentration of sevoflurane that must be added to 63% N2 O (approximate equals 2/3 MAC) to prevent patient movement is approximately 0.66% (approximate equals 1/3 MAC) [2]. These authors concluded that the MAC fraction of N2 O must be added to the MAC fraction of sevoflurane to compute the total anesthetic effect. Thus, to account for the effect of 50% N2 O, computed MAC equivalents for sevoflurane and isoflurane must each be increased by approximately 0.5 MAC, resulting in effective concentrations of 3.4 and 4.8 MAC for 5% sevoflurane and isoflurane, respectively. In contrast, Abramson and Pivalizza have incorrectly assumed that, since 0.66% sevoflurane added to 63% N2 O yields an anesthetic depth of 1 MAC, each additional 0.66% of sevoflurane adds an additional MAC to the effective depth of anesthesia. This line of reasoning results in the following inconsistency: 5% sevoflurane in O2 corresponds to 2.9 MAC, while 5% sevoflurane in 63% N2 O is equivalent to 7.5 MAC! In conclusion, single-breath inhaled induction of anesthesia with sevoflurane offers a suitable alternative to an intravenous induction in selected patients, especially when an 8% initial concentration is administered. Mark H. Sloan, MD Peter K. Karsunky, MD Pattilyn F. Conard, CRNA, MA Jeffrey B. Gross, MD* *JBG is a lecturer and consultant for Abbott Laboratories. Department of Anesthesiology, University of Connecticut School of Medicine, Farmington, CT 06030-2015

Sevoflurane Versus Isoflurane

Because of its nonpungent odor and low blood-gas solubility coefficient, sevoflurane might be an ideal drug for single-breath inhaled induction of anesthesia. Fifty ASA grade I-III ambulatory surgical patients (18-76 yr old) received a single-breath induction with either 5.0% sevoflurane or 5.0% isoflurane (randomized) in a 1:1 N2O/O2 mixture. Anesthesia was maintained with the same anesthetic in 70% N2O until the end of surgery, when anesthetics were abruptly discontinued. Induction times (loss of eyelash reflex) were similar for sevoflurane (75 +/- 3 s, mean +/- se) and isoflurane (67 +/- 4 s, P = not significant). Sevoflurane patients were less likely to have complications during induction (P < 0.005); coughing occurred more frequently with isoflurane (P < 0.001). During induction, heart rate increased with both sevoflurane (from 73 +/- 3 to 90 +/- 4 bpm, P < 0.05) and isoflurane (from 70 +/- 2 to 92 +/- 2 bpm, P < 0.05); the increase with isoflurane was greater than that with sevoflurane. Times to eye opening for sevoflurane (8.1 1 +/- 1.0 min) did not differ significantly from those for isoflurane (10.6 +/- 1.3 min). Patients opened their eyes at lower end-tidal minimum alveolar anesthetic concentration (MAC)-fractions of sevoflurane (0.12 +/- 0.01 MAC) than isoflurane (0.15 +/- 0.01 MAC, P < 0.01). During recovery, patients who received sevoflurane felt less clumsy (P < 0.001) and less confused (P < 0.005) but had higher pain scores (P < 0.005) than those who received isoflurane. Sevoflurane is more suitable than isoflurane for single-breath induction, because it produces a smoother induction with a lower incidence of complications and better patient acceptance.

Onset Time of Neuromuscular Block as a Function of the Period of Baseline Stabilization

In Response: We would like to thank Dr. Kopman for his interesting and important observations on our study examining the onset of neuromuscular block [1]. The influence of the duration of anesthesia including the use of nitrous oxide may well be important and is being investigated. Nitrous oxide, however, with its low blood-gas solubility, equilibrates rapidly and would have influenced the results in the groups with shorter periods of control stimulation. Our results showed a progressive reduction in the onset time throughout the period of study. Although the influence of an increase in muscle temperature may affect the electromyographic recordings [2], there is no evidence at present about its influence on evoked twitch tension. Moreover, the authors of this study commented that "the correlation between the EEMG response and the muscle temperature in the study may be coincidental." There may be many reasons for the increase in muscle blood flow, including the duration of control stimulation and the duration of anesthesia itself prior to administration of the relaxant, but whatever the cause, both Dr. Kopman and we agree that standardization of these variables would make for better comparison of data from different investigators. The mechanisms of increase in the blood flow to the muscle itself need further investigation. E. P. McCoy, FFARCSI R. K. Mirakhur, MD F. M. Connolly, FFARCSI P. B. Loan, FRCA Department of Anaesthetics, The Queen's University of Belfast, Belfast, Northern Ireland

Aufwachzeiten, Kreislaufverhalten und unerwünschte Wirkungen bei Anwendung von Sevofluran und Enfluran - Eine offene, randomisierte, vergleichende Phase III-Studie

Sevoflurane is a "new" volatile inhaled anaesthetic currently undergoing phase III clinical trials in Europe and USA. Owing to the low blood solubility, rapid induction of anaesthesia and emergence from anaesthesia would be expected. In this study, we compared emergence times and haemodynamics in patients receiving either sevoflurane or enflurane. Furthermore, all adverse experiences were recorded, and the relationship to the drug administered was rated. Thirty ASA physical status I and II patients were studied in an open, prospective and randomised clinical trial. Anaesthesia was induced with fentanyl, thiopentone and vecuronium for facilitating endotracheal intubation. Anaesthesia was maintained with sevoflurane or enflurane, 60% nitrous oxide in oxygen and additional doses of fentanyl (1-2 micrograms/kg/h). ECG, blood pressure (non-invasive), inspiratory and end-tidal concentrations of sevoflurane or enflurane were monitored continuously. At the end of surgery, administration of sevoflurane or enflurane and nitrous oxide stopped without tapering and emergence times were recorded. All adverse experiences which occurred until the third postoperative day were recorded and the relationship to the inhaled anaesthetic was rated as "none", "unlikely", "possible", "probable" or "highly probable". With the exception of the end-tidal concentration at the end of surgery and the mean inspiratory and end-tidal concentrations, which were higher for sevoflurane, the two patient groups were comparable. Pulmonary elimination was significantly faster and emergence time was significantly shorter (5 vs. 9 minutes) with sevoflurane. Emergence time did not correlate with the duration of anaesthetic exposure (MAC hours) for sevoflurane. There was no difference in the time courses of heart rate and mean arterial blood pressure between sevoflurane and enflurane. No adverse experiences with a "probable" or "highly probable" relationship to the inhaled anaesthetic were observed. Emergence time after inhalation anaesthesia depends on (alveolar) ventilation, blood-gas solubility coefficient and, at least for enflurane and isoflurane, on the dose applied (MAC hours). There is no positive correlation between emergence time and dose applied for sevoflurane. Due to the lower blood-gas solubility coefficient (0.6-0.7 for sevoflurane vs. 1.8 for enflurane) pulmonary elimination is faster and emergence time is shorter with sevoflurane. Supplementing inhalation anaesthesia with fentanyl, there is no difference in the time courses of heart rate and mean arterial blood pressure between sevoflurane and enflurane.

Consequences of misfilling contemporary vaporizers with desflurane.

Desflurane is a volatile anaesthetic that combines low blood gas solubility (blood/gas partition coefficient = 0.42 at 37 degrees C), moderate potency (MAC = 6-7%), and high volatility (vapour pressure = 681 mmHg at 20 degrees C, boiling point = 23.5 degrees C). The volatility and potency of desflurane prevent its safe use in vaporizers of traditional design. We present a mathematical model which demonstrates the potential for desflurane overdose if contemporary vaporizers are misfilled with desflurane. The most hazardous filling error occurs if an enflurane vaporizer is misfilled with desflurane. The calculated desflurane output of a misfilled enflurane vaporizer at a dial setting of 1% and a temperature of 22 degrees C is 57.8%, or 9.6 MAC. For misfilled enflurane, isoflurane, and halothane vaporizers at dial settings equivalent to one MAC at 22 degrees C, the calculated desflurane output is 14.0, 10.2, and 7.8 MAC, respectively. We conclude that the safe delivery of desflurane will require engineering safeguards, additional monitoring, and education of the anesthesia community.

New drugs and new understandings of paediatric pharmacology

lnhalational anaesthetic agents The uptake and elimination of the inhaled anaesthetic agents in infants and children have been extensively studied. The high level of alveolar ventilation compared to the functional residual capacity, the larger proportion of vessel rich tissues, and a lower blood gas solubility coefficient all contribute to the rapid induction and recovery phases which occur in the infant. Inhalation anaesthetic agents are probably metabolized less in infants than in older patients; serum bromide levels are lower following halothane in infants than in adults. Serum inorganic fluoride levels are lower following enflurane anaesthesia, but this may also be due to increased bone deposition of fluoride in paediatric patients. The effects of the volatile anaesthetics on the cardiorespiratory system of infants and chidren are now more fully documented, lsoflurane causes an increase in heart rate and halothane slows the heart. At equal levels of anaesthesia, halothane and isoflurane cause a similar degree of hypotension which is dose-related. Isoflurane, however, causes less depression of myocardial contractility but more afterload reduction than halothane. Cardiac output is better maintained with isoflurane provided fluid is administered to maintain preload. 2 The addition of nitrous oxide to the inspired gas mixture results in cardiovascular effects which are similar to those produced by equianaesthetic dose levels of the volatile agents in oxygen. 3 While the volatile anaesthetics all cause similar increases in end-tidal carbon dioxide levels in spontaneously breathing children the patterns of ventilation differ. Depression of the ventilatory response to carbon dioxide is dose-dependent. Halothane causes tachypnoea, isoflurane causes little change in rate, and enflurane tends to slow ventilation. 4 Intercostal muscle activity is suppressed by haiothane, paradoxical breathing occurs at end-tidal concentrations above one per cent. 5 Intravenous anaesthetics and analgesics The dose requirements of thiopentone in infants and children of various ages show wide variation. Newborn infants require 3-4 mg.kg -I while those of 1-6 mo require 7-8 mg.kg-~. 6 In healthy children 5-6 mg. kg-i is the dose required for rapid reliable induction of anaesthesia. 7 The pharmacokinetics of thiopentone in paediatric patients have been studied and show a shorter elimination time in infants and children than in adults) The narcotic analgesics have been widely used in infants, especially for major surgical procedures, fentanyl being the most commonly used drug. The dose response of neonates to fentanyl indicate that a dose 10-12.5 I~g kg -I will prevent any response to surgical stimulation and provide anaesthesia for 60-90 min. 9 Older infants may require higher doses. I~ The pharmacokinetics of fentanyl depend upon age. Neonates show wider variation and slower clearance rates than older infants, who may demonstrate clearance rates higher than those of adults. ~ Preterm infants and neonates with increased intraabdominal pressure predictably demonstrate a prolonged elimination half-life of the drug. J2 Some infants demonstrate secondary peaks in plasma levels of the drug and these may be associated with respiratory depression in patients not on mechanical ventilation. The cardiovascular system is little affected by even large doses of fentanyl, but a useful effect in blunting the neonatal pulmonary vascular responses to stress has been noted. Chest wall compliance is significantly reduced by fentanyl in children.

Clinical pharmacokinetics of the inhalational anaesthetics.

At present, the most widely used inhalational anaesthetics are the halogenated, inflammable vapours halothane, enflurane, isoflurane and the gas nitrous oxide. The anaesthetic effect of these agents is related to their tension or partial pressure in the brain, represented at equilibrium by the alveolar concentration. The minimum alveolar concentration for a specific agent is remarkably constant between individuals. The uptake and distribution of inhalational anaesthetics depends on inhaled concentration, pulmonary ventilation, solubility in blood, cardiac output and tissue uptake. Inhalational anaesthetics are mainly eliminated by pulmonary exhalation, but significant amounts of halothane are removed by hepatic metabolism. Inhalational agents currently in use have acceptable pharmacokinetic characteristics, and clinical acceptance depends on their potential for adverse effects. Induction of anaesthesia with halothane is rapid and relatively pleasant and it is the agent of choice for paediatric anaesthesia. Between 20 and 50% is metabolised, and the parent drug is a potent inhibitor of drug metabolism. Post-operatively enzyme induction may follow. The major disadvantages of halothane are myocardial depression, propensity to evoke cardiac arrhythmias and the rare but serious halothane hepatitis. Induction and recovery from enflurane anaesthesia is rapid. Metabolism accounts for 5 to 9% of the elimination. The metabolic product inorganic fluoride may in rare cases cause renal toxicity. Enflurane is a weak inhibitor of drug metabolism at anaesthetic concentrations. Enflurane depresses circulation more than halothane by reducing both myocardial contractility and systemic vascular resistance, but cardiac rhythm is stable. Enflurane anaesthesia may, unlike the other agents, induce epileptic activity. Enflurane is widely used as replacement for halothane in adults. Despite its low blood-gas solubility, the airway irritability of isoflurane precludes a faster induction of anaesthesia than with halothane. Isoflurane is almost resistant to biodegradation. Myocardial contractility is maintained during isoflurane anaesthesia and cardiac rhythm is stable except for the occurrence of tachycardia in some patients. Isoflurane is the inhalational agent of choice for neurosurgical operations. Sevoflurane is an experimental ether vapour: induction and recovery is fast and pleasant. It is metabolised to the same extent as enflurane and subnephrotoxic concentrations of inorganic fluoride may result. Sevoflurane has fewer respiratory and cardiovascular depressant effects than halothane and may be a future alternative for paediatric anaesthesia.(ABSTRACT TRUNCATED AT 400 WORDS)

Enflurane et circulation extracorporelle. Effets vasculaires périphériques et conséquences de l'hypothermie sur sa biotransformation

The effects of enflurane on systemic vascular resistance and venous capacitance, and its biotransformation during hypothermia, were studied in patients undergoing cardiovascular surgery with enflurane anaesthesia. When administered during cardiopulmonary bypass (CPB), cardiac regulatory mechanisms being therefore excluded, enflurane induced an arteriolar vasodilation related to the concentration inhaled. An inspired concentration of 2.5 % in hypertermia (28 °C) produced a drop in systemic vascular resistance of 30 % from control level. In the same conditions, venous capacitance was not altered. The rise in the blood gas solubility coefficient during hypothermia was only partly balanced by haemodilution. Therefore, inspired enflurane concentration should be higher during hypothermic CPB than during normothermic anaesthesia to obtain the same effects. For the same amount of enflurane inhaled, the fraction of enflurane metabolized was higher in hypothermia than in normothermia, but the inorganic fluoride plasma concentration at its highest never reached the level of 50 μmol · l −1 regarded as the nephrotoxic threshold.

Isobaric inert gas supersaturation: observations, theory, and predictions

An isobaric inert gas supersaturation model incorporating both diffusion and perfusion properties of biological tissue is presented in a form which allows ready comparison with experimental observations. This model requires only measurement of inert gas flux and blood gas solubility in order to evaluate "counterdiffusion potential". Inert gas flux across the skin of Yorkshire piglets anesthetized with pentobarbital was measured for He, Ne, CH4, C2H4, N2O, and SF6. Model predictions based upon these data compare favorably with published reports of isobaric inert gas supersaturation, as well as several previously unpublished observations. The possibility of supersaturation resulting from the use of hydrogen as a breathing gas in a helium environment is also discussed, and extensive animal testing is recommended before potentially dangerous human exposure occurs.

PULMONARY CLEARANCE OF ANAESTHETIC AGENTS A Theoretical Study

The pulmonary clearance of anaesthetic agents (Cl) represents a useful index of their elimination from the lungs. Its value depends on pulmonary blood flow (), alveolar ventilation (VA), and anaesthetic blood solubility (λ) according to equation: Cl = (VAQ)/(VA+λQ). When the alveolar ventilation and pulmonary blood flow are constant the pulmonary clearance of the anaesthetic depends on its blood solubility. In this case the lower the blood solubility is, the higher the value of pulmonary clearance becomes. For each anaesthetic agent a change in alveolar ventilation or in pulmonary blood flow will produce a change in pulmonary clearance which in its turn depends on anaesthetic blood solubility. When λ = (VA/Q)2 a change in alveolar ventilation or in pulmonary blood flow will affect the pulmonary clearance to the same extent. When the anaesthetic blood solubility value is higher than (VA/Q)2, its pulmonary clearance is predominantly affected by alveolar ventilation, and when anaesthetic blood solubility is lower than (VA/Q)2 its pulmonary clearance is predominantly dependent on pulmonary blood flow. Changes in pulmonary clearance produced by changes in alveolar ventilation (/VA) are larger with halothane, nitrous oxide and cyclopropane than with agents of greater blood-gas solubility at all VA/Q ratios in the range 0.5—2.0.