The in-vitro effects of sevoflurane and desflurane on the contractility of pregnant human uterine muscle

The effect of desflurane and sevoflurane on the contractility of the uterus was examined in vitro on strips of human myometrium obtained at the time of elective cesarean section. Small strips (1 mm x 2 mm x 10 mm) of muscle were prepared and suspended in an organ bath containing oxygenated physiological saline. Force of contraction was recorded continuously using an isometric tension transducer. Following the onset of regular spontaneous contractions, baseline measurements were obtained and the strips were exposed to varying concentrations of sevoflurane or desflurane corresponding to 0.5, 1.0 and 1.5 minimum alveolar concentration (MAC). Sevoflurane depressed contractility to 72 +/- 18% of control at 0.5 MAC, 37 +/- 15% at 1.0 MAC and 27 +/- 16% at 1.5 MAC compared with 65 +/- 14 of control at 0.5 MAC, 43 +/- 18% at 1.0 MAC and 22 +/- 11% at 1.5 MAC for desflurane. The degree of depression of uterine muscle contractility produced by both these agents was significantly different from control at all concentrations. In conclusion, both sevoflurane and desflurane depress the contractility of isolated pregnant human myometrium at concentrations of 0.5, 1.0 and 1.5 MAC. These agents produce a similar degree of depression of uterine muscle contractility.     

Effects of volatile anesthetics on directly and indirectly stimulated skeletal muscle.

Isolated guinea pig nerve-lumbrical muscle preparations were exposed to halothane, methoxyflurane, isoflurane, enflurane, fluroxene, and diethyl ether. The temporal courses of the effects on indirectly and directly elicited twitch responses were determined over a range of concentrations for each agent. When the anesthetics were compared at concentrations equivalent in terms of minimum alveolar concentration (MAC), a spectrum was observed in which halothane, methoxyflurane and isoflurane depressed the indirect twitch response at 3.5--5 MAC and the direct twitch response at 8--10 MAC. Diethyl ether and fluroxene depressed the indirect twitch response at 2--3.5 MAC and the direct twitch response at 3--6 MAC. Enflurane depressed the indirect response at 1.5--2.5 MAC and the direct response at 6--8 MAC. When the anesthetics were compared at concentrations equivalent in terms of their abilities to depress end-plate depolarization, however, all anesthetics were equipotent. Depression of the indirect twitch response occurred only when anesthetic concentrations were great enough to depress depolarization by 50 per cent.     

Supplementing desflurane with intravenous anesthesia reduces fetal cardiac dysfunction during open fetal surgery

Objective: To lower the incidence and severity of fetal cardiovascular depression during maternal fetal surgery under general anesthesia. Aim: We hypothesized that supplemental intravenous anesthesia (SIVA) with propofol and remifentanil would lower the need for high‐dose inhalational anesthesia and provide adequate maternal depth of anesthesia and uterine relaxation. SIVA technique would minimize prolonged fetal exposure to deep inhalational anesthetics and significant intraoperative fetal cardiovascular depression. Background: Fetal hypoxia and significant fetal hemodynamic changes occur during open fetal surgery because of the challenges such as surgical manipulation, hysterotomy, uterine contractions, and effects of anesthetic drugs. Tocolysis, a vital component of fetal surgery, is usually achieved using volatile anesthetic agents. High concentrations of volatile agents required to provide an appropriate degree of uterine relaxation may cause maternal hypotension and placental hypoperfusion, as well as direct fetal cardiovascular depression. Methods: We reviewed medical records of 39 patients who presented for ex utero intrapartum treatment and mid‐gestation open fetal surgery between April 2004 and March 2009. Out of 39 patients, three were excluded because of the lack of echocardiographic data; 18 patients received high‐concentration desflurane anesthesia and 18 patients had SIVA with desflurane for uterine relaxation. We analyzed the following data: demographics, fetal medical condition, anesthetic drugs, concentration and duration of desflurane, maternal arterial blood pressure, intraoperative fetal echocardiogram, presence of fetal bradycardia, and need for intraoperative fetal resuscitation. Results: Adequate uterine relaxation was achieved with about 1.5 MAC of desflurane in the SIVA group compared to about 2.5 MAC in the desflurane only anesthesia group (P = 0.0001). More fetuses in the high‐dose desflurane group compared to the SIVA group developed moderate‐severe left ventricular systolic dysfunction over time intraoperatively (P = 0.02). 61% of fetuses in the high‐dose desflurane group received fetal resuscitative interventions compared to 26% of fetuses in the SIVA group (P = 0.0489). Conclusion: SIVA as described provides adequate maternal anesthesia and uterine relaxation, and it allows for decreased use of desflurane during open fetal surgery. Decreased use of desflurane may better preserve fetal cardiac function.     

Alteration of left ventricular diastolic function by desflurane, isoflurane, and halothane in the chronically instrumented dog with autonomic nervous system blockade

The effects of the new volatile anesthetic desflurane on three indices of left ventricular diastolic function were examined and compared to those produced by equianesthetic concentrations of isoflurane and halothane. Diastolic function has been shown to significantly influence systolic performance, but the effects of volatile anesthetics on diastolic function have not been extensively examined. Since autonomic nervous system function may significantly influence hemodynamic actions of anesthetics in vivo, experiments were performed in the presence of pharmacologic blockade of the autonomic nervous system. Three groups comprising a total of 23 experiments were performed using 11 dogs instrumented for measurement of aortic and left ventricular pressure, rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, and cardiac output. Systemic hemodynamics were recorded in the conscious state and after 30 min equilibration at 1.0 and 1.5 MAC desflurane, isoflurane, or halothane. Ventricular relaxation was described using invasively derived time constants of isovolumetric relaxation with zero (To) or nonzero (Tn) assumptions of asymptotic decay. Chamber and myocardial stiffness the viscoelastic properties of the ventricle, were described using exponential relationships relating ventricular pressure to segment length and end-diastolic pressure to Lagrangian strain, respectively. Desflurane produced a significant (P less than 0.05) and dose-dependent increase in isovolumetric relaxation as a evaluated by both time constants (To, 22.2 +/- 2.0 during control to 33.9 +/- 3.5 ms at 1.5 MAC; Tn, 33.1 +/- 1.6 during control to 45.1 +/- 4.3 ms at 1.5 MAC). Similar degrees of prolongation of isovolumetric relaxation were produced by isoflurane (Tn, 35.6 +/- 1.5 during control to 47.1 +/- 2.9 ms at 1.5 MAC) and halothane (Tn, 31.7 +/- 2.2 during control to 42.3 +/- 3.9 ms at 1.5 MAC). Halothane also caused an increase in regional passive chamber stiffness (Kp, 0.46 +/- 0.07 during control to 0.88 +/- 0.17 mm-1 at 1.5 MAC) indicating a decrease in ventricular compliance. No changes in chamber stiffness were observed with desflurane or isoflurane. In addition, no significant changes in myocardial stress-strain relationships as evaluated by nonlinear elastic coefficients, alpha (gain) and beta (myocardial stiffness), were observed with any anesthetic. Although the effects of volatile anesthetics on systolic function could not be entirely excluded from the analysis, the results indicated that desflurane, isoflurane, and halothane produce equivalent degrees of prolongation of isovolumetric relaxation. Halothane also caused a decrease in compliance during passive filling as evaluated by chamber stiffness, but no change in compliance was observed at end diastole as assessed by stress-strain relationships.(ABSTRACT TRUNCATED AT 400 WORDS)     

Relaxation of rat gastrointestinal smooth muscle by parathyroid hormone

In this study we investigated whether parathyroid hormone (PTH) can produce relaxation of gastrointestinal (GI) smooth muscle as it has been reported to do for vascular and uterine smooth muscle. Muscle tissue preparations from rat stomach, duodenum, ileum, or colon were mounted in a 37 degrees C tissue bath and perfused with oxygenated medium. Changes in isometric tension were recorded with a force-displacement transducer connected to a polygraph. Decreases in either resting tension or agonist-induced tension (0.5-1.0 microM acetylcholine or carbachol) were observed within 1-2 min of PTH addition and were reversible upon removal of the peptide. All GI regions tested were responsive to PTH. Synthetic rPTH-(1-34) (0.1-100 nM) produced a dose-dependent relaxation of both fundic (ED50 = 5.2 nM) and colonic (ED50 = 2.5 nM) muscle strips. At 100 nM, a 90% decrease in fundic tension and a 70% decrease in colonic tension were seen. At 100 nM, bPTH-(1-34), but not bPTH-(7-34) or rat calcitonin gene-related peptide, also was effective in relaxing fundic or colonic muscle. Similarly, in the fundic muscle, 500 nM bPTH-(3-34) alone was ineffective, but it inhibited the effect of 5 nM rPTH-(1-34) when both peptides were tested in combination. Likewise, 100 nM bPTH-(3-34) also inhibited the relaxation induced by 5, 10, or 100 nM bPTH-(1-34). The results show PTH to be highly effective in nanomolar concentrations in causing relaxation of GI smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anesthetic management of the ex-utero intrapartum treatment (EXIT) procedure for congenital high airway obstruction syndrome (CHAOS)

We report an experience of anesthetic management of the ex-utero intrapartum treatment (EXIT) procedure performed in a fetus with congenital high airway obstruction syndrome (CHAOS) due to laryngeal atresia at 30 weeks' gestation. Anesthesia of the mother was induced with rapid sequence, and maintained with 3.5% sevoflurane in 100% oxygen and fentanyl before delivery. Two minimum alveolar concentration (MAC) sevoflurane provided excellent uterine relaxation without maternal hypotension. After hysterotomy, a sterile pulse oxymeter was placed on the fetus hand for monitoring fetal SpO2 and pulse rate, and a Doppler ultrasound transducer was applied to monitor fetal heart rate. Fentanyl (5 microg x dl(-1)) and pancuronium (0.2 mg x dl(-1)) were injected into the fetal upper arm in addition to transplacental anesthetic agents. The fetal heart rate and SpO2 were stable throughout the fetal manipulations, but the rise in SpO2 after initiating ventilation via tracheostomy was very slow. The uterine tone improved soon after discontinuing sevoflurane and oxytocin infusion was started after delivery. Surfactant administration before first ventilation is recommended in preterm babies undergoing EXIT procedure, and capnometer may be useful to confirm the adequate ventilation before cutting the umbilical cord.     

Combined depressant effects of diltiazem and volatile anesthetics on contractility in isolated ventricular myocardium

Because the volatile anesthetics depress the entry of calcium (Ca) into myocardial cells and also alter release of intracellular Ca stores, additional pharmacologic blockade of Ca entry could potentially enhance anesthetic-induced depression. The depressant effects of the calcium entry blocker diltiazem combined with the volatile anesthetics halothane, enflurane, or isoflurane were investigated in isolated guinea pig papillary muscle. Muscle contractions were studied in normal Tyrode solution after rest and at stimulation rates of 0.1, 0.25, 0.5, 1, 2, and 3 Hz. Anesthetics were studied in the presence of 0.1 and 1 microM diltiazem, which depressed tension to approximately 85 and 55% of control at 2-3 Hz, respectively; depression at the higher concentration was frequency-dependent. Depressant effects of enflurane were determined as previously done for equianesthetic concentrations (approximately 1 and 2 MAC) of halothane and isoflurane. At all stimulation rates, 1.7 and 3.5% enflurane depressed peak tension and dT/dt-max to approximately 73 and 50% of the mean control-recovery value, respectively. After control measurements of contractile characteristics, effects of 0.1 microM diltiazem were determined alone and then with the addition of halothane (0.75 or 1.5%), isoflurane (1.3 or 2.5%), or enflurane (1.7 or 3.5%), respectively. Recovery from anesthetic was then determined in the continued presence of diltiazem. After rest and at rates less than or equal to 0.5 Hz, equianesthetic concentrations of these volatile agents caused similar depression in the presence of diltiazem. At 3 Hz stimulation rate, 1.3% isoflurane caused significantly less contractile depression than did 1.7% enflurane or than 0.75% halothane. At 2-MAC concentrations, differences among the anesthetics were more apparent: 2.5% isoflurane depressed peak tension and dT/dt-max less than did halothane at 1-3 Hz stimulation rates, and depressed dT/dt-max less than 3.5% enflurane at 2-3 Hz. Similar frequency-dependent differences in depression by approximately 2 MAC anesthetics were observed in the presence of 1 microM diltiazem. The patterns of depressant action by the volatile anesthetics were similar to those previously observed in the absence of diltiazem. Furthermore, when the volatile anesthetic depression of contractions was combined with the depression due to diltiazem-induced blockade of Ca entry, the resulting contractile depression did not differ significantly from a prediction that assumed simply additive effects.     

Comparative effects of halothane, enflurane, and isoflurane at equipotent anesthetic concentrations on isolated ventricular myocardium of the ferret. II. Relaxation

The effects of halothane, enflurane, and isoflurane on myocardial relaxation were compared in papillary muscles of the right ventricle of adult male ferrets at 30 degrees C. The sensitivity of cardiac relaxation to the loading conditions was determined by examining the time course of relaxation before, during, and after exposure to incremental concentrations of halothane (n = 9 muscles), enflurane (n = 9 muscles), and isoflurane (n = 9 muscles) in steps of 0.25 MAC up to 1.5 MAC of halothane and of enflurane and up to 2.0 MAC of isoflurane. Load sensitivity of relaxation was quantified by comparing force and time coordinates at the onset of the isometric relaxation phase in several afterloaded isotonic twitch contractions with relaxation of the isometric twitch. Load sensitivity of relaxation, which is of particular benefit during early rapid filling of the heart, was decreased in a dose-dependent reversible fashion by halothane, enflurane, and, to a lesser extent, by isoflurane. These anesthetics abbreviated isometric relaxation, yet prolonged the time course of muscle lengthening which is suggestive of an impairment of calcium uptake by the sarcoplasmic reticulum and of a decrease in calcium sensitivity of the contractile proteins.     

Alternating nitroglycerin and syntocinon to facilitate uterine exploration and removal of an adherent placenta

Nitroglycerin (NTG) has been demonstrated to provide uterine relaxation in the management of various obstetric complications. A 32-yr-old woman presented 40 min postpartum for manual removal of a retained placenta. Repeated, alternating doses of NTG 250 μg and syntocinon (SYN) 10Uiv were used over 15 min to produce periods of uterine relaxation and contraction respectively for uterine exploration. Multiple attempts to extract the placenta failed and a diagnosis of placenta accreta was made. There were no major side effects from this combination of drugs apart from a transient 20% decrease in blood pressure after NTG, which responded to ephedrine 10– 15 mg iv. The rapid change in uterine tone was believed to be due not only to the short duration of action of NTG and SYN, but also to the possible physiological antagonism between the two drugs. The mechanism of interaction may involve calcium mobilization and myosin light chain phosphorylation. We conclude that NTG and SYN can be used to produce alternating periods of uterine relaxation and contraction rapidly and consistently with little sustained effects from either agents.     

A new preparation of nitroglycerin for uterine relaxation

Emergent attainment of uterine relaxation is an occasional need in obstetric practice. Various agents, from amyl nitrate through volatile anesthetics have been used to relax the uterus, with varying degrees of success and side-effects. Recent publications report the use of intravenous nitroglycerin (NTG), with excellent results and few adverse side effects, but preparation for injection requires time and may produce error. We have used a new sublingual aerosol spray of NTG, at an initial dose of 0.8 mg, in 7 patients for rapid uterine relaxation and have not observed adverse side-effects. Prolonged shelf life, ready availability and ease of use make the sublingual spray attractive for urgent tocolysis.     

Rates of awakening from anesthesia with I-653, halothane, isoflurane, and sevoflurane: a test of the effect of anesthetic concentration and duration in rats

The low blood solubility of two new inhaled anesthetics, I-653 (human blood/gas partition coefficient, 0.42) and sevoflurane (0.69), suggested that awakening from these agents should be more rapid than awakening from currently available anesthetics such as isoflurane (1.4) and halothane (2.5). This prediction proved valid in a study of these four agents in rats given 0.4, 0.8, 1.2, or 1.6 MAC for 2.0 hr or 1.6 MAC for 0.5 or 1.0 hr. At a given dose and duration, awakening was most rapid with the least soluble agent and longest with the most soluble agent. For example, recovery of muscle coordination at 1.2 MAC administered for 2 hr required 4.7 +/- 3.0 min (mean +/- SD) with I-653, 14.2 +/- 8.1 min with sevoflurane, 23.2 +/- 7.6 min with isoflurane, and 47.2 +/- 4.7 min with halothane.     

The effects of enflurane,isoflurane, and intravenous anesthetics on rat diaphragmatic function and fatigability

We examined the effect of isoflurane, enflurane, midazolam, ketamine, propofol, and thiopental on diaphragmatic functions under unfatigued and fatigued conditions in 228 rat isolated muscle strips. Diaphragmatic twitch characteristics and tetanic contractions were measured before and after muscle fatigue, which was induced by repetitive tetanic contraction with or without exposure to one of the anesthetics at clinically relevant plasma concentrations, and at 10 and 100 times this concentration, or at 1, 2, and 3 minimum alveolar anesthetic concentration (MAC). Isoflurane, midazolam, ketamine, propofol, and thiopental did not induce a direct inotropic or lusitropic effect under unfatigued and fatigued conditions. Enflurane did not change contraction or relaxation in fresh isolated diaphragm, but enflurane at 2-3 MAC enhanced diaphragmatic fatigability itself and fatigue-induced impairment of twitch characteristics and tetanic tensions. These effects were greater at 3 MAC than at 2 MAC. Our findings suggest that the reduction of diaphragm function previously reported in in vivo experiments using propofol, midazolam, and isoflurane is not related to a direct effect on intrinsic diaphragmatic contractility. Our results also indicate that large concentrations of enflurane may impair the diaphragmatic function at sites other than excitation-contraction coupling. IMPLICATIONS: Enflurane did not change contraction or relaxation in fresh isolated rat diaphragm, but enhanced diaphragmatic fatigability itself and fatigue-induced impairment of twitch characteristics and tetanic tensions. Isoflurane, midazolam, ketamine, propofol, and thiopental had no direct effects on diaphragmatic functions under unfatigued and fatigued conditions. Isoflurane and these i.v. anesthetics may be advantageous over enflurane to anesthetize and/or sedate patients who are predisposed to diaphragmatic fatigue.     

Comparison of calcium antagonist properties of antispasmotic agents

Several agents commonly employed for the treatment of detrusor hyperreflexia or instability are characterized as antispasmotics. Their mechanism of action is not completely understood but it has been proposed that their actions are dependent on anticholinergic activity, CNS mediated relaxation, or local anesthetic properties. The purpose of this study was to determine if imipramine, flavoxate HCl, or oxybutynin HCl possess any calcium antagonist properties. This was accomplished by determining the ability of these agents to inhibit a standard cholinergic stimulus (200 uM bethanechol) over a range of extracellular calcium concentrations (0.5 to 10.0 mM). In-vitro isolated smooth muscle strips of rabbit bladder dome were utilized. Control tissues displayed a reproducible response to bethanechol stimulation at different calcium concentrations with an ED50 of 0.4 mM calcium and a peak response of 5.0+/-0.4 grams tension. Flavoxate (2.5 mM), oxybutynin (2.5 uM), and imipramine 25 uM) all significantly reduced peak tension generation. The ED 50's for extracellular calcium in the presence of flavoxate and oxybutynin were not significantly different from controls. Imipramine at both 3 and 25 uM significantly increased the ED50 for calcium. The above data demonstrate that imipramine possesses competitive calcium antagonism. The relative contribution of calcium antagonism toward the inhibitory effects of imipramine is unknown but may play a significant role in its clinical activity.     

Halothane, enflurane, and isoflurane attenuate both receptor- and non-receptor-mediated EDRF production in rat thoracic aorta.

EDRF (endothelium-derived relaxing factor) is a cellular and intercellular messenger that activates soluble guanylate cyclase. In blood vessels it is released from the endothelium and causes relaxation of vascular smooth muscle. Halothane previously has been shown to attenuate EDRF-induced vasodilation elicited by the receptor-mediated vasodilators acetylcholine and bradykinin and to alter muscarinic receptor activity. We examined and compared the effects of the inhaled anesthetics halothane, enflurane, and isoflurane on endothelium-dependent vasodilation and tested the hypothesis that these agents inhibit EDRF-mediated vasodilation solely through inhibition of endothelial cell receptor-mediated EDRF release. Isolated rat thoracic aortic rings were mounted for isometric tension recording and preconstricted with phenylephrine. Cumulative dose-response curves were obtained to methacholine, a receptor-mediated endothelium-dependent dilator; to A23187, a nonreceptor-mediated endothelium-dependent dilator; and to sodium nitroprusside, a direct-acting endothelium-independent dilator before, during, and after inhalational anesthetic exposure. Both receptor-mediated and non-receptor-mediated endothelium-dependent relaxation by methacholine and A23187, respectively, were significantly (P less than 0.01 to P less than 0.05) and reversibly attenuated by halothane, enflurane, and isoflurane at 2 MAC and by isoflurane at 1 MAC. Endothelium-independent relaxation by sodium nitroprusside, an agent that acts directly on the vascular smooth muscle cell to activate guanylate cyclase, was unaffected by any of the anesthetics at any concentration tested. Indomethacin had no significant effect on the inhibition of endothelium-dependent vasodilation by these inhalational anesthetics. We conclude that halothane, enflurane, and isoflurane inhibit endothelium-dependent vasodilation; that isoflurane is more potent than halothane and enflurane in this regard.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulatory and catecholamine responses to tracheal intubation and skin incision during sevoflurane, isoflurane, or halothane anesthesia

The anesthetic suppression of responses to noxious stimuli might reflect a summation of the suppression of the basal functions and the response capability. We investigated the basal suppression and response capability in hemodynamics and plasma catecholamine levels with different anesthetics at the same minimum alveolar concentration (MAC) level. Fifty-four patients were allocated to one of 6 groups to receive sevoflurane, isoflurane, or halothane at 1.25 or 2.0 MAC. Anesthesia was induced with the test agent in oxygen and the end-tidal concentration of the agent was maintained for at least 15 min at 1.25 or 2.0 MAC. The trachea was intubated under muscle relaxation with 0.1 mg·kg⁻¹ vecuronium. Skin incisions were made after maintaining the end-tidal concentration of the agent for at least 15 min after tracheal intubation. The mean arterial pressure, heart rate, rate-pressure product, and plasma levels of noradrenaline and adrenaline at the prestimuli period showed no difference between agents at each MAC. The rises in these variables by tracheal intubation and skin incision were greatest in the sevoflurane group, least in the halothane group, and intermediate in the isoflurane group. Although basal hemodynamic suppression is similar at the same MAC, the suppressive action of sevoflurane on the circulatory response capability to noxious stimuli is weaker than that of isoflurane and halothane. This study was presented in part at the 42nd annual congress of the Japan Society of Anesthesiology, April 20, 1995     

The effect of neuromuscular blockade with vecuronium on hemodynamic responses to noxious stimuli in the rat

The effect of neuromuscular blockade with vecuronium on the hemodynamic responses to a noxious stimulus was investigated in male Sprague-Dawley rats. The rats were anesthetized with either halothane (group 1, n = 10), or isoflurane (group 2, n = 10). The maximum values for heart rate and mean arterial pressure during the noxious stimulus (base-tail clamp) were measured, and the maximum changes in these values (maximum minus prestimulation) were calculated. The responses were measured at two different anesthetic concentrations (0.6 X MAC, 0.75 X MAC), before and after vecuronium 1.0 mg.kg-1 iv. It was found that neuromuscular blockade with vecuronium did not reduce any of the hemodynamic responses measured, at either anesthetic concentration, in either the halothane or the isoflurane group. However, increasing the anesthetic concentration from 0.6 X MAC to 0.75 X MAC produced statistically significant (P less than 0.01) reductions in several of the responses measured. The inability of vecuronium to reduce hemodynamic responses to noxious stimuli in this study suggests that neuromuscular blockade does not alter anesthetic depth in the rat. A knowledge of this "absence of effect" may be important for investigators who need to induce muscle relaxation in laboratory animals prior to examining the effect of anesthetic agents on hemodynamic responses to noxious stimuli. The results also question the ability of neuromuscular blockade to reduce anesthetic requirement, and support the view that neuromuscular blockade does not contribute to the anesthetic state.     

Pulmonary mechanics during isoflurane,sevoflurane and desflurane anaesthesia

This study was designed to investigate the effects of desflurane on bronchial smooth muscle tone, following intubation and to compare these effects with isoflurane and sevoflurane. Patients were randomly divided into three groups to receive, isoflurane (n = 22), sevoflurane (n = 23), or desflurane (n = 22). Peak inspiratory pressure (PIP), respiratory resistance (Rr) and dynamic compliance (Cdyn) measurements were recorded at three time points; After the beginning of ventilation and before inhalation agent was started, following 5 min of ventilation with 1 MAC (minimum alveolar concentration) inhalation agent and following 5 min of 2 MAC inhalation agent. We found that all inhalation agents caused a significant decrease in Peak Inspiratory Pressure (PIP) and respiratory resistance (Rr), and an increase in dynamic compliance (Cdyn) at 1 MAC concentrations. When the agent concentration was increased to 2 MAC, desflurane caused a significant increase in Rr and PIP and a decrease in Cdyn. We concluded that desflurane, like isoflurane and sevoflurane, exhibits a bronchodilator effect at 1 MAC concentration. However, increasing the concentration to 2 MAC caused an increase in airway resistance with desflurane, whilst sevoflurane and isoflurane continued to have a bronchodilator effect.     

Is isoflurane a calcium antagonist?

The vasodilating and myocardial depressant effects of isoflurane have been allocated to calcium channel blockade. The present study aimed to test this hypothesis by assessing the effect of isoflurane on the contractile response to potassium stimulation of vascular smooth muscle. Seventy two left anterior descending and circumflex coronary artery rings were removed in twelve dogs and mounted in organ chambers filled with Krebs-Ringer bicarbonate solution and aerated with 95% O2-5% CO2. Rings were pretreated with either 3.8% isoflurane (2.5 MAC in the dog) or 10(-8) mol.l-1 nifedipine, a calcium entry blocker. They were stimulated by addition of 10 to 150 mmol.l-1 potassium chloride. At 70 mmol.l-1 K+, the tension generated by the untreated rings was 119 +/- 4.25% of control, while in the isoflurane treated group the tension was 99 +/- 2.4% of control. In the opposite, the tension was 25 +/- 7.11% in the nifedipine treated rings. Likewise, when isoflurane was added to rings preconstricted with 40 mmol.l-1 potassium chloride, no relaxation occurred, while nifedipine produced relaxation. Isoflurane, unlike nifedipine, had a weak effect on ring tension. The calcium-entry blockade effect of isoflurane appeared weak, dose-dependent and virtually absent at clinical concentrations. Therefore, the vasodilation seen with clinical concentrations of isoflurane is mediated by mechanisms other than calcium-entry blockade.     

Comparison of the effects of sevoflurane and isoflurane anesthesia on the maternal-fetal unit in sheep

Purpose  The aim of this study was to determine the hemodynamic and blood gas effects of inhalational anesthetics on the maternal-fetal sheep unit. The principal hypothesis, tested in chronically instrumented near-term pregnant ewes, was that sevoflurane anesthesia may be safe and useful for the mother and fetus during pregnancy, compared with isoflurane. Methods  Six chronically instrumented pregnant and 3 nonpregnant ewes were tested repeatedly to establish the minimum alveolar concentration (MAC) for sevoflurane and isoflurane to be used in the hemodynamic and blood gas studies. Progressively increasing concentrations of sevoflurane or isoflurane in oxygen were administered to 12 pregnant ewes. Uterine blood flow, maternal and fetal heart rates, blood pressure, arterial blood gases, and intra-amniotic pressure were subsequently measured. Results  The MAC of sevoflurane was 1.52 ± 0.1 15% and 1.92 ± 0.17% in pregnant and nonpregnant ewes, respectively; while the MAC of isoflurane in the pregnant and nonpregnant sheep was 1.02 ± 0.12% and 1.42 ± 0.19%, respectively. In both the sevoflurane and isoflurane groups, changes in maternal and fetal blood gases were minimal during exposure to low-dose (0.5–1.0 MAC) inhaled concentrations. Although uterine blood flow was maintained and the fetus remained well oxygenated at higher concentrations of both agents (2.0 MAC of either agent), the agents produced decreases in maternal and fetal arterial pressure. Conclusion  A “low-dose” concentration (0.5–1.0 MAC) of sevoflurane may be safe and useful for both mother and fetus during near-term pregnancy. However, a high concentration (1.5–2.0 MAC) of sevoflurane or isoflurane may induce hemodynamic instability in the mother and fetus when administered.     

Pulsed Doppler and two-dimensional echocardiography: comparison of halothane and isoflurane on cardiac function in infants and small children

The combination of two-dimensional and pulsed Doppler echocardiography was used to measure determinants of cardiac function in 20 ASA physical status I infants and small children (9 days-32 months of age) during equipotent halothane (n = 10) or isoflurane (n = 10) anesthesia in oxygen. Five sets of cardiovascular data were recorded in each patient. In the awake, unmedicated state prior to induction, at three different anesthetic levels, 0.75, 1.0, and 1.25 MAC (corrected for age) and a final measurement repeated at 1.25 MAC after the intravenous infusion of 15 ml X kg-1 of Lactated Ringers solution. The study was completed prior to intubation and surgery. Results are expressed as mean +/- SEM. Isoflurane and halothane decreased mean blood pressure from the awake level (isoflurane 76.6 +/- 2.3 to 60.6 +/- 3.1 mm, halothane 72.2 +/- 3.9 to 60.6 +/- 3.1 mm at 1.25 MAC). Isoflurane increased heart rate at all anesthetic levels (128.7 +/- 4.2 to 142.5 +/- 6.0 beats/min at 0.75 MAC). Halothane decreased heart rate at 1.25 MAC (124.6 +/- 4.6 to 119.4 +/- 3.5 beats/min). Isoflurane and halothane decreased cardiac index at 1.25 MAC. Stroke volume index decreased at 1.0 and 1.25 MAC with both isoflurane (36.9 +/- 3.8 to 30.2 +/- 3.5 ml/m2) and halothane (32.7 +/- 2.5 to 28.9 +/- 2.5 ml/m2). Ejection fractions also decreased significantly at 1.0 and 1.25 MAC in both groups of patients (22 +/- 6% at 1.25 MAC halothane and 28 +/- 8% at 1.25 MAC isoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)