The effects of sevoflurane, isoflurane, halothane, and enflurane on hemodynamic responses during an inhaled induction of anesthesia via a mask in humans

A rapid increase in isoflurane or desflurane concentration induces tachycardia and hypertension and increases-plasma catecholamine concentration. Little information is available as to whether sevoflurane, halothane, and enflurane induce similar responses during anesthesia induction via mask. Fifty ASA physical status I patients, aged 20-40 yr, and scheduled for elective minor surgery, received one of four volatile anesthetics: sevoflurane, isoflurane, halothane, or enflurane. Anesthesia was induced with thiamylal, followed by inhalation of 0.9 minimum alveolar anesthetic concentration (MAC) of the anesthetic in 100% oxygen via mask. The inspired concentration of anesthetic was increased by 0.9 MAC every 5 min to a maximum of 2.7 MAC. Heart rate (HR) and systolic blood pressure (SBP) were measured before and every minute for 15 min during anesthetic inhalation. In the sevoflurane and isoflurane groups, venous blood samples were drawn to determine the concentrations of plasma epinephrine and norepinephrine 3 min after each increase in anesthetic concentration. Sustained increments in HR were observed after increases in inspired isoflurane concentration to 1.8 MAC and 2.7 MAC (peak changes of 15 +/- 3 and 17 +/- 3 bpm, respectively). Isoflurane also increased SBP transiently after the inspired concentration was increased to 2.7 MAC (peak change of 10 +/- 4 mm Hg). Enflurane increased HR after the inspired concentration was increased to 2.7 MAC (peak change of 9 +/- 2 bpm). In contrast, changes in sevoflurane and halothane concentrations did not induce hyperdynamic responses. Plasma norepinephrine concentration in the isoflurane group was significantly higher than that in the sevoflurane group during 2.7 MAC (P = 0.022). We propose that there is a direct relationship between airway irritation of the anesthetic and immediate cardiovascular change during an inhaled induction of anesthesia.     

Halothane, isoflurane, and sevoflurane reduce postischemic adhesion of neutrophils in the coronary system

BACKGROUND: Polymorphonuclear neutrophils (PMNs) contribute to postischemic reperfusion damage in many organs and tissues, a prerequisite being adhesion of PMNs to vascular endothelial cells. Because adhesion processes involve orderly interactions of membrane proteins, it appeared possible that "membrane effects" of volatile anesthetics could interfere. We investigated the effects of halothane, isoflurane, and sevoflurane on postischemic adhesion of human PMNs in the intact coronary system of isolated perfused guinea pig hearts. METHODS: The hearts (n = 7-10 per group) were perfused in the "Langendorff" mode under conditions of constant flow (5 ml/min) using modified Krebs-Henseleit buffer equilibrated with 94.4% oxygen and 5.6% carbon dioxide. Global myocardial ischemia was induced by interrupting perfusion for 15 min. In the second minute of reperfusion (5 ml/min), a bolus dose of 6 x 10(5) PMNs was injected into the coronary system. The number of cells reemerging in the coronary effluent was expressed as a percentage of the total number of applied PMNs. Halothane, isoflurane, and sevoflurane, each at 1 and 2 minimal alveolar concentration (MAC), were vaporized in the gas mixture and applied from 14 min before ischemia until the end of the experiment. RESULTS: Under nonischemic conditions, 24.7 +/- 1.3% of the injected neutrophils did not reemerge from the perfused coronary system. Subjecting the hearts to global ischemia augmented retention (36.4 +/- 2.8%, P < .05). Application of halothane reduced adhesion of neutrophils to 22.6 +/- 2.1% and 24.2 +/- 1.8% at 1 and 2 MAC, respectively (P < .05). Exposure to 1 and 2 MAC isoflurane was similarly effective, whereas basal adhesion was not significantly influenced. Sevoflurane-treated hearts (1 and 2 MAC) also showed decreased adhesion of PMNs (23 +/- 2.3% and 24.8 +/- 1.8%, respectively; P < .05) and an identical reduction resulted when sevoflurane (1 MAC) was applied only with the onset of reperfusion. CONCLUSIONS: Although the mechanism of action of volatile anesthetics remains unclear in these preliminary studies, their inhibitory effect on ischemia-induced adhesion of PMNs may be beneficial for the heart during general anesthesia.     

Cerebral blood flow velocity in relation to cerebral blood flow, cerebral metabolic rate for oxygen, and electroencephalogram analysis during isoflurane anesthesia in dogs

The purpose of this study was to correlate changes in cerebral blood flow velocity (Vmean) with cerebral blood flow (CBF) during isoflurane anesthesia in dogs. The relation between cerebral oxygen consumption (CMRO2) and electroencephalogram (EEG) analysis also was investigated. Blood flow velocity was measured in the middle cerebral artery using a pulsed transcranial Doppler (TCD). CBF was measured with radioactive microspheres. EEG was measured over both hemispheres and median EEG frequency (median frequency) was calculated after fast Fourier transformation. Baseline anesthesia was maintained with 50% nitrous oxide in oxygen and 50 micrograms.kg-1 x h-1 fentanyl. Animals of Group I (control, n = 6) were not given isoflurane. Data were recorded at baseline, and at 30, 60, and 90 min. There was no significant change in any variable over time. In Group II (n = 7), data were recorded at baseline and at 1%, 2%, and 3% end-tidal isoflurane. Mean arterial pressure was maintained at baseline levels by phenylephrine infusion. CBF increased from 70.8 +/- 10.6 mL.100g-1 x min-1 at baseline to 146.1 +/- 36.9 mL.100 g-1 x min-1 with 3% isoflurane (P < 0.01). Vmean increased from 38.3 +/- 6.7 cm/s to 65.6 +/- 9.7 cm/s (P < 0.01). The correlation between relative changes in CBF and Vmean was r = 0.94 (P < 0.01). With 1% isoflurane the EEG shifted to slow-wave, high-voltage activity, and median frequency decreased from 5.9 +/- 0.7 Hz to 1.4 +/- 0.4 Hz (P < 0.05). Median frequency was not decreased further during 2% and 3% isoflurane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of halothane, isoflurane and desflurane on lower oesophageal sphincter tone

We have studied the effects of volatile anaesthetics on lower oesophageal sphincter (LOS) tone in three groups of eight pigs allocated randomly to receive end-tidal concentrations of 0.5, 1.0 and 1.5 MAC of desflurane, isoflurane or halothane for 15 min. LOS and oesophageal barrier pressures (BrP = LOSP - gastric pressure) were measured using a manometric method. The decrease in BrP paralleled the decrease in LOS pressure and was significant at 0.5 MAC for isoflurane and at 1.0 MAC for halothane. At 1.5 MAC, BrP values were approximately 62% of baseline values for halothane, 37% for isoflurane and 83% for desflurane. Inter-group comparisons showed that BrP did not differ at baseline and at 0.5 MAC. At 1.0 MAC the effect of isoflurane on BrP was significantly different from desflurane (P < 0.001) and halothane (P < 0.02) whereas the effect of desflurane on BrP was not significantly different from halothane. At 1.5 MAC the effect of isoflurane on BrP was significantly different from desflurane (P < 0.01) and halothane (P < 0.05) whereas the effect of desflurane on BrP was not significantly different from halothane. We conclude that desflurane maintained BrP and this may be clinically important in patients at high risk of regurgitation.     

Delayed onset of malignant hyperthermia induced by isoflurane and desflurane compared with halothane in susceptible swine

BACKGROUND: Desflurane (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether) is a new inhalational anesthetic currently under investigation for use in humans. Recently, the authors showed that desflurane is a trigger of malignant hyperthermia (MH) in susceptible swine. To date, there has been no in vivo comparison of the relative ability of inhalational anesthetics to trigger MH. The effects of desflurane, isoflurane, and halothane on six MH-susceptible purebred and six MH-susceptible mixed-bred Pietrain swine were examined. METHODS: The animals were exposed to 1 MAC and 2 MAC (if MH was not triggered after 1 MAC hour) doses of each of the three volatile anesthetics in random sequence at 7-10-day intervals and changes in end-tidal CO2, arterial blood gases, serum lactate, core and muscle temperature, blood pressure, and heart rate were measured. RESULTS: There was a statistical difference between anesthetics in the time required to trigger MH; halothane exposure resulted in the fastest onset of an MH episode (20 +/- 5 min), compared with isoflurane (48 +/- 24 min) and desflurane (65 +/- 28 min), both of which required significantly longer exposures. There was no statistical difference between the MH purebred and mixed-bred swine in the time required to trigger MH (defined as a PaCO2 of 70 mmHg) with a given agent, and time to triggering was also independent of the order of exposure to the three anesthetics. Malignant hyperthermia susceptibility was confirmed in ten surviving animals, by both in vivo succinylcholine challenge and in vitro contracture testing. CONCLUSIONS: Although all three volatile anesthetics triggered MH, exposure to halothane resulted in significantly shorter times to MH triggering when compared with desflurane and isoflurane.     

Effects of isoflurane on in vivo release of acetylcholine in the rat cerebral cortex and striatum

BACKGROUND: Acetylcholine (ACh) is one of the major excitatory neurotransmitters in the central nervous system, and changes in neural activity induced by anesthesia alter the release of ACh. However, the effects of isoflurane, one of the most widely used volatile anesthetics, on ACh release are not known. The present study attempts to clarify the dose-effect relationship of isoflurane on the in vivo release of ACh in rat brains. METHODS: Changes in the extracellular concentration of ACh and choline in the cerebral cortex and striatum induced by 0.5, 1.0, and 1.5 minimum alveolar concentration (MAC) of isoflurane were determined using a brain microdialysis technique. RESULTS: In the cortex, the ACh release decreased to 30.8+/-10.1 (mean+/-SEM), 10.2+/-4.1, and 8.1+/-2.9% of basal value by increasing doses of isoflurane, and in the striatum, to 73.3+/-4.4, 49.2+/-4.2, and 40.7+/-4.5%. The ACh release rapidly recovered control levels with the discontinuance of isoflurane. Choline concentration was not changed significantly by isoflurane except for a decrease to 74.8+/-4.6% in the striatum by 0.5 MAC. In both the cortex and striatum, the choline concentration decreased with the discontinuance of isoflurane to 70.3+/-13.3, and 68.2+/-5.4%, respectively. CONCLUSION: The fact that all classic anesthetics reported previously, as well as isoflurane, reduce ACh release supports the hypothesis that the suppression of cholinergic cells is, at least in part one of the mechanisms of anesthesia.     

Effects of sevoflurane or halothane on contractile responses of isolated canine basilar artery

Although volatile anesthetic is known as a cerebral vasodilator, its mechanism is not clear. The purpose of this study was to investigate effects of sevoflurane or halothane on contractions induced by high K+ and serotonin in the isolated canine basilar artery. Cylindrical segments of canine basilar artery were placed in Krebs solution oxygenated with 95% O2 and 5% CO2 at 37 degrees C. They were then constricted with cumulative administration of 10 to 60 mM KCl, or with 10(-9) to 10(-6) M serotonin and exposed to either sevoflurane or halothane at concentration of 1.0 and 2.0 MAC. Halothane and sevoflurane at concentration of 1.0 and 2.0 MAC decreased contractile responses evoked by KCl to a similar degree. The attenuation by either of the two anesthetics at concentration of 2.0 MAC were equivalent to the inhibitions by diltiazem 2 x 10(-7) M. Contractile responses to serotonin above 3 x 10(-7) M were depressed by halothane 1.0 MAC, but not by sevoflurane 1.0 MAC. Sevoflurane and halothane at concentration of 2.0 MAC decreased contractile responses evoked by serotonin at concentrations above 3 x 10(-8) M and 10(-8) M. Removal of the endothelium did not alter the response of the basilar artery contracted by serotonin to either anesthetic. These findings suggest that sevoflurane and halothane depress the voltage-dependent Ca2+ channels due to decreases of contractile responses to high K+. Our results also demonstrate that sevoflurane is a less potent vasodilator of the basilar artery contracted by serotonin than halothane.     

Changing from isoflurane to desflurane toward the end of anesthesia does not accelerate recovery in humans

BACKGROUND: In an attempt to combine the advantage of the lower solubilities of new inhaled anesthetics with the lesser cost of older anesthetics, some clinicians substitute the former for the latter toward the end of anesthesia. The authors tried to determine whether substituting desflurane for isoflurane in the last 30 min of a 120-min anesthetic would accelerate recovery. METHODS: Five volunteers were anesthetized three times for 2 h using a fresh gas inflow of 2 l/min: 1.25 minimum alveolar concentration (MAC) desflurane, 1.25 MAC isoflurane, and 1.25 MAC isoflurane for 90 min followed by 30 min of desflurane concentrations sufficient to achieve a total of 1.25 MAC equivalent ("crossover"). Recovery from anesthesia was assessed by the time to respond to commands, by orientation, and by tests of cognitive function. RESULTS: Compared with isoflurane, the crossover technique did not accelerate early or late recovery (P > 0.05). Recovery from isoflurane or the crossover anesthetic was significantly longer than after desflurane (P < 0.05). Times to response to commands for isoflurane, the crossover anesthetic, and desflurane were 23 +/- 5 min (mean +/- SD), 21 +/- 5 min, and 11 +/- 1 min, respectively, and to orientation the times were 27 +/- 7 min, 25 +/- 5 min, and 13 +/- 2 min, respectively. Cognitive test performance returned to reference values 15-30 min sooner after desflurane than after isoflurane or the crossover anesthetic. Isoflurane cognitive test performance did not differ from that with the crossover anesthetic at any time. CONCLUSIONS: Substituting desflurane for isoflurane during the latter part of anesthesia does not improve recovery, in part because partial rebreathing through a semiclosed circuit limits elimination of isoflurane during the crossover period. Although higher fresh gas flow during the crossover period would speed isoflurane elimination, the amount of desflurane used and, therefore, the cost would increase.     

Prolonged sevoflurane, isoflurane and halothane anaesthesia in oxygen using rebreathing or non-rebreathing system in cats

Effects of prolonged sevoflurane, isoflurane and halothane anaesthesia in oxygen on clinical, cardiopulmonary, haematologic, and serum biochemical findings were compared in healthy, premedicated cats breathing spontaneously during 6 h of anaesthesia using rebreathing (semi-closed circuit) or non-rebreathing (Bain coaxial circuit) system. Recovery from anaesthesia with sevoflurane was more rapid than that with halothane or isoflurane in both systems. Respiration and heart rates during sevoflurane anaesthesia were similar to those during isoflurane rather than halothane anaesthesia in both systems. The degree of respiratory acidosis during prolonged sevoflurane anaesthesia was similar to that during isoflurane anaesthesia, and was less than that during halothane anaesthesia in both rebreathing and non-rebreathing systems. Prolonged sevoflurane anaesthesia induced mean arterial pressure similar to isoflurane or halothane anaesthesia in the non-rebreathing system, but it depressed mean arterial pressure less than isoflurane or halothane anaesthesia in the rebreathing system. Time related increase in the arterial carbon dioxide partial pressure was observed during halothane anaesthesia especially in the rebreathing system, however, no significant time-related changes in cardiopulmonary variables were observed during either sevoflurane or isoflurane anaesthesia in both systems. There were no significant differences among sevoflurane, isoflurane and halothane anaesthesia in serum biochemical values in both systems.     

The effects of propofol, isoflurane, and sevoflurane on oxygenation and shunt fraction during one-lung ventilation

Propofol's effect on hypoxic pulmonary vasoconstriction during one-lung ventilation (OLV) has not been determined. Twenty patients who had long-term OLV for esophageal surgery were allocated randomly to one of two study groups; one in which isoflurane administration preceded propofol, and another in which sevoflurane administration preceded propofol. Arterial and mixed venous blood samples and hemodynamics were measured as follows: before OLV, during OLV, OLV at 4 cm of positive end-expiratory pressure (PEEP), OLV after conversion from volatile anesthetics to propofol, OLV at 4 cm of PEEP, and after OLV. After the application of 4 cm of PEEP during propofol anesthesia, PaO2 increased significantly in both groups. The shunt fraction (Qs/Qt) increased significantly after the initiation of OLV in both groups and decreased significantly after the conversion from volatile anesthetics to propofol in both groups. Propofol can be used safely during OLV because PaO2 increased after the application of 4 cm of PEEP during propofol anesthesia, and Qs/Qt decreased significantly after the conversion from inhaled anesthetics to propofol anesthesia. IMPLICATIONS: During one-lung ventilation, the arterial partial pressure of oxygen values with propofol were greater than those with isoflurane and sevoflurane, and shunt fraction values with propofol were lower than those with both volatile anesthetics. Propofol improved oxygenation and shunt fraction during one-lung ventilation compared with volatile anesthetics.     

Regional deposition and retention of particles in shallow, inhaled boluses: effect of lung volume

We evaluated the effects of volatile anesthetics on T-type calcium current (ICa,T) present in four different cell types using the whole cell version of the patch clamp technique. In dorsal root ganglion neurons and in two neuroendocrine cells--adrenal glomerulosa cells (AG) and thyroid C-cells--ICa,T was reversibly decreased by volatile anesthetics at clinically relevant concentrations, with isoflurane and enflurane being more potent that halothane. In AG cells, the most sensitive cell type tested, ICa,T was reduced 47%+/-4% (n = 6) by isoflurane (0.7 mM) and 56%+/-2% (n = 5) by enflurane (1.2 mM), but by only 24%+/-1% (n = 5; P < 0.05) by halothane (0.7 mM). Isoflurane caused a significant increase in the rate of deactivation of ICa,T in AG cells. In ventricular myocytes, however, ICa,T was much less sensitive to both isoflurane and halothane. The differential sensitivity of ICa,T in various cell types to the anesthetics may reflect differences in the channels expressed in these tissues or differences in the cellular intermediates involved in anesthetic action. Depression of ICa,T in neuronal cells may contribute to anesthetic action through decreases in cellular excitability. IMPLICATIONS: Using the patch clamp technique, we showed that T-type calcium channels, which promote cellular excitability, are inhibited by volatile anesthetics in neuronal and neuroendocrine cells, but not in ventricular myocytes. Inhibition of neuronal T-type channels may contribute to the mechanism of action of volatile anesthetics.     

Enflurane and isoflurane, but not halothane, protect against myocardial reperfusion injury after cardioplegic arrest with HTK solution in the isolated rat heart

To investigate the effects of halothane, enflurane, and isoflurane on myocardial reperfusion injury after ischemic protection by cardioplegic arrest, isolated perfused rat hearts were arrested by infusion of cold HTK cardioplegic solution containing 0.015 mmol/L Ca2+ and underwent 30 min of ischemia and a subsequent 60 min of reperfusion. Left ventricular (LV) developed pressure and creatine kinase (CK) release were measured as variables of myocardial function and cellular injury, respectively. In the treatment groups (each n = 9), anesthetics were given during the first 30 min of reperfusion in a concentration equivalent to 1.5 minimum alveolar anesthetic concentration of the rat. Nine hearts underwent the protocol without anesthetics (controls). Seven hearts underwent ischemia and reperfusion without cardioplegia and anesthetics. In a second series of experiments, halothane was tested after cardioplegic arrest with a modified HTK solution containing 0.15 mmol/L Ca2+ to investigate the influence of calcium content on protective actions against reperfusion injury by halothane. LV developed pressure recovered to 59%+/-5% of baseline in controls. In the experiments with HTK solution, isoflurane and enflurane further improved functional recovery to 84% of baseline (P < 0.05), whereas halothane-treated hearts showed a functional recovery similar to that of controls. CK release was significantly reduced during early reperfusion by isoflurane and enflurane, but not by halothane. After cardioplegic arrest with the Ca2+-adjusted HTK solution, halothane significantly reduced CK release but did not further improve myocardial function. Isoflurane and enflurane given during the early reperfusion period after ischemic protection by cardioplegia offer additional protection against myocardial reperfusion injury. The protective actions of halothane depended on the calcium content of the cardioplegic solution. IMPLICATIONS: Enflurane and isoflurane administered in concentrations equivalent to 1.5 minimum alveolar anesthetic concentration in rats during early reperfusion offer additional protection against myocardial reperfusion injury even after prior cardioplegic protection. Protective effects of halothane solely against cellular injury were observed only when cardioplegia contained a higher calcium concentration.     

No effects of high-dose omeprazole in patients with severe airway hyperresponsiveness and (a)symptomatic gastro-oesophageal reflux

Uptake of inhaled anesthetics may be measured as the amount of anesthetic infused to maintain a constant alveolar concentration of anesthetic. This method assumes that the patient absorbs all of the infused anesthetic, and that none is lost to circuit components. Using a standard anesthetic circuit with a 3-L rebreathing bag simulating the lungs, and simulating metabolism by input of carbon dioxide, we tested this assumption for halothane, isoflurane, and sevoflurane. Our results suggest that after washin of anesthetic sufficient to eliminate a material difference between inspired and end-tidal anesthetic, washin to other parts of the circuit (probably the ventilator) and absorbent (soda lime) continued to remove anesthetic for up to 15 min. From 30 min to 180 min of anesthetic administration, circuit components absorbed trivial amounts of isoflurane (12 +/- 13 mL vapor at 1.5 minimum alveolar anesthetic concentration, slightly more sevoflurane (39 +/- 15 mL), and still more halothane (64 +/- 9 mL). During this time, absorbent degraded sevoflurane (321 +/- 31 mL absorbed by circuit components and degraded by soda lime). The amount degraded increased with increasing input of carbon dioxide (e.g., the 321 +/- 31 mL increased to 508 +/- 48 mL when carbon dioxide input increased from 250 mL/min to 500 mL/min). Measurement of anesthetic uptake as a function of the amount of anesthetic infused must account for these findings. Implications: Systems that deliver inhaled anesthetics may also remove the anesthetic. Initially, anesthetics may diffuse into delivery components and the interstices of material used to absorb carbon dioxide. Later, absorbents may degrade some anesthetics (e.g., sevoflurane). Such losses may compromise measurements of anesthetic uptake.     

Neuromuscular effects of rocuronium during sevoflurane, isoflurane, and intravenous anesthesia

The potency and time course of action of rocuronium were studied in patients anesthetized with 66% nitrous oxide in oxygen and 1.5 minimum alveolar anesthetic concentration of sevoflurane or isoflurane, or a propofol infusion. Potency was estimated by using the single-bolus technique. Neuromuscular block was measured by stimulation of the ulnar nerve and by recording the force of contraction of the adductor pollicis muscle. The mean (95% confidence limits) of the 50% and 95% effective doses were estimated tobe 142 (129-157) and 265 (233-301) microg/ kg, 165 (146-187) and 324 (265-396) microg/kg, and 183 (163-207) and 398 (316-502) microg/kg during sevoflurane, isoflurane, and propofol anesthesia, respectively (P < 0.05 for sevoflurane versus propofol). The mean +/- SD times to onset of maximal block after rocuronium 0.6 mg/kg were 0.96 +/- 0.16, 0.90 +/- 0.16, and 1.02 +/- 0.15 min during sevoflurane, isoflurane, and propofol anesthesia, respectively. The respective times to recovery of the first response in the train-of-four (TOF) stimulation (T1) to 25% and 90% were 45 +/- 13.1 and 83 +/- 29.3 min, 35 +/- 6.1 and 56 +/- 15.9 min, and 35 +/- 9.2 and 55 +/- 19.4 min. The times to recovery of the TOF ratio to 0.8 were 103 +/- 30.7, 69 +/- 20.4, and 62 +/- 21.1 min, and the 25%-75% recovery indices were 26 +/- 11.7, 12 +/- 5.0, and 14 +/- 6.9 min, respectively. There were no differences among groups in the times for onset of action or to recovery of T1 to 25%. However, the times for recovery of T1 to 90%, TOF ratio to 0.8, and recovery index in the sevoflurane group were all significantly longer compared with the other two groups (P < 0.05, < 0.01, and < 0.01, respectively). We conclude that the effects of rocuronium, especially duration of action, are significantly enhanced during sevoflurane compared with isoflurane and propofol anesthesia. IMPLICATIONS: In routine clinical use, the effects of rocuronium are enhanced by sevoflurane, in comparison with isoflurane and propofol anesthesia, and the recovery is slower. Particular attention should be paid to monitoring of neuromuscular block during sevoflurane anesthesia.     

Roles of Rho-associated kinase in cytokinesis; mutations in Rho-associated kinase phosphorylation sites impair cytokinetic segregation of glial filaments

The effects of sevoflurane on myocardial contraction and relaxation are poorly understood. Therefore, we studied the effects of equianaesthetic concentrations (0.5, 1, 1.5, 2 and 2.5 MAC) of sevoflurane, isoflurane and halothane on inotropic and lusitropic (myocardial relaxation) variables, and post-rest potentiation in rat left ventricular papillary muscles in vitro. Sevoflurane and isoflurane caused comparable concentration-dependent negative inotropic effects which were significantly lower than those induced by halothane (P < 0.05). Sevoflurane and isoflurane did not modify lusitropic variables under low or high load, whereas halothane showed a negative lusitropic effect at high concentrations. Halothane suppressed post-rest potentiation, whereas isoflurane and sevoflurane did not. Post-rest recovery was unaffected by halothane, isoflurane or sevoflurane at any concentration. Thus in rat myocardium, sevoflurane and isoflurane caused comparable negative inotropic effects, had no significant lusitropic effects and did not alter post-rest potentiation, suggesting that they did not significantly modify the functions of the sarcoplasmic reticulum.     

A phase III, multicenter, open-label, randomized, comparative study evaluating the effect of sevoflurane versus isoflurane on the maintenance of anesthesia in adult ASA class I, II, and III inpatients

STUDY OBJECTIVE: To compare the clinical efficacy and safety of sevoflurane and isoflurane when used for the maintenance of anesthesia in adult ASA I, II, and III inpatients undergoing surgical procedures of at least 1 hour's duration. DESIGN: Phase III, randomized, open-label clinical trial. SETTING: 12 international surgical units. PATIENTS: 555 consenting inpatients undergoing surgeries of intermediate duration. INTERVENTIONS: Subjects received either sevoflurane (n = 272) or isoflurane (n = 283) as their primary anesthetic drug, each administered in nitrous oxide (N2O) (up to 70%) and oxygen (O2) after an intravenous induction using thiopental and low-dose fentanyl. The concentration of volatile drug was kept relatively constant but some titration in response to clinical variable was permitted. Comparison of efficacy was based on observations made of the rapidly and ease of recovery from anesthesia and the frequency of untoward effects for the duration of anesthesia in the return of orientation. Safety was evaluated by monitoring adverse experiences, hematologic and non-laboratory testing, and physical assessments. In 25% of patients (all patients 171 both treatment groups at selected investigational sites), plasma inorganic fluoride concentrations were determined preoperatively, every 2 hours during maintenance, at the end of anesthesia, and at 1, 2, 4, 8, 12, 24, 48, and 72 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Emergence, response to commands, orientation, and the first request for postoperative analgesia were all more rapid following discontinuation of sevoflurane than following discontinuation of isoflurane (sevoflurane, 11.0 +/- 0.6, 12.8 +/- 0.7, 17.2 +/- 0.9, 46.1 +/- 3.0 minutes, respectively, versus isoflurane, 16.4 +/- 0.6, 18.4 +/- 0.7, 24.7 +/- 0.9, 55.4 +/- 3.2 minutes). The incidence of adverse experiences was similar for sevoflurane and isoflurane patients. Forty-eight percent of patients on the sevoflurane group had no untoward effect versus 39% in the isoflurane group. Three patients who received sevoflurane had serum inorganic fluoride levels 50 microM/I. or greater though standard tests indicated no evidence of associated renal dysfunction. CONCLUSION: Sevoflurane anesthesia, as compared with isoflurane, may be advantageous in providing a smoother clinical course with a more rapid recover.     

Isoflurane and halothane do not alter the enhanced afterload sensitivity of left ventricular relaxation in dogs with pacing-induced cardiomyopathy

BACKGROUND: The afterload dependence of left ventricular (LV) relaxation is accentuated in the failing heart. The authors tested the hypothesis that isoflurane and halothane alter the afterload sensitivity of LV relaxation in dogs with pacing-induced cardiomyopathy. METHODS: Dogs (n = 6) were chronically instrumented for measurement of LV and aortic pressures and subendocardial segment length. Hemodynamics were recorded, and LV relaxation was evaluated with a time constant of isovolumic relaxation (tau) under control conditions and during decreases and increases in LV load produced by abrupt inferior vena caval (IVC) occlusion and phenylephrine (intravenous infusion), respectively, in the conscious state and during isoflurane and halothane anesthesia (1.5 MAC) on separate days before and after the development of pacing-induced cardiomyopathy. The slope (R) of the tau versus LV end-systolic pressure (P[es]) relation was also used to determine the afterload sensitivity of LV relaxation. RESULTS: IVC occlusion and phenylephrine produced similar or less profound changes in P(es), regional end-systolic force (an index of LV afterload), and end-systolic segment length in cardiomyopathic compared with healthy dogs. However, IVC occlusion and phenylephrine caused more pronounced alterations in tau in conscious and isoflurane- and halothane-anesthetized dogs after the development of cardiomyopathy. R was also greater in cardiomyopathic compared with healthy dogs (e.g., 0.32 +/- 0.03 before pacing to 1.00 +/- 0.13 ms/mmHg in conscious dogs). No differences in the load dependence of LV relaxation were observed between the conscious and anesthetized states before and after production of LV dysfunction. CONCLUSIONS: The results indicate that isoflurane and halothane do not alter the afterload dependence of LV relaxation in the normal and cardiomyopathic heart. The lack of effect of the volatile anesthetics is probably related to anesthetic-induced reductions in the resistance to LV ejection concomitant with simultaneous negative inotropic effects.     

Inhibition of sodium/calcium exchange and calcium channels of heart cells by volatile anesthestics

BACKGROUND: Volatile anesthetics exert profound effects on the heart, probably through their effect on Ca2+ movements during the cardiac cycle. Ca2+ movements across the sarcolemma are thought to involve mainly Ca2+ channels and the Na+/Ca2+ exchanger. We have therefore investigated the action of halothane, isoflurane, and enflurane on Na+/Ca2+ exchange and Ca2+ channel activity to assess the contribution of these pathways to the observed effect of the anesthetics on the myocardium. METHODS: Sarcolemmal ion fluxes were investigated using radioisotope uptake by isolated adult rat heart cells in suspension. Na+/Ca2+ exchange activity was measured from 45Ca2+ uptake by Na(+)-loaded cells. Ca2+ channel activity was measured from verapamil-sensitive trace 54Mn2+ uptake during electric stimulation. RESULTS: Halothane, isoflurane, and enflurane inhibited Na+/Ca2+ exchange completely, with similar potency when concentrations were expressed in millimolar units in aqueous medium but not when expressed as minimum alveolar concentration (MAC). The inhibition by enflurane was particularly strong, > 50%, at 2 MAC. In contrast, the three anesthetics inhibited Ca2+ channels with similar potency when concentrations were expressed as MAC but not when expressed in millimolar units in aqueous medium. Hill plots of pooled data with all three anesthetics showed a slope of -3.87 +/- 0.50 for inhibition of Na+/Ca2+ exchange and -1.73 +/- 0.19 for inhibition of Ca2+ channels. CONCLUSIONS: Halothane, isoflurane, and enflurane inhibit both Na+/Ca2+ exchange and Ca2+ channels at concentrations relevant to anesthesia, although they exhibit differences in potency and number of sites of action. At 1.5 MAC, halothane inhibits Ca2+ channels more than Na+/Ca2+ exchange, whereas enflurane inhibits Na+/Ca2+ exchange more than Ca2+ channels. Isoflurane inhibited both systems equally. The inhibition of Ca2+ influx by these agents is likely to contribute to their negative inotropic effect in the heart. The inhibition of Na+/Ca2+ exchange by enflurane may account for its observed action of delaying relaxation in species lacking sarcoplasmic reticulum.     

Isoflurane potency in the dog and cat

Cardiopulmonary effects of isoflurane, a new inhalation anesthetic, were investigated in healthy unpremedicated dogs and cats under conditions of spontaneous and controlled (dogs only) ventilation. Measurements were made at minimal alveolar concentration (MAC) multiples of 1.0, 1.5, 2.0, and 3.0 in dogs and 1.0, 1.5, 2.0, and 2.4 in cats. The isoflurane MAC was previously determined in these animals and was 1.28 +/- 0.06% for dogs and 1.63 +/- 0.02% for cats. We found that as anesthetic dose increased, mean arterial pressure consistently and significantly (P less than 0.05) decreased. Cardiac output, measured only in dogs, was sustained only during light-moderate levels (1.0 to 2.0 MAC) of anesthesia because the heart rate significantly increased. Stroke volume, total peripheral resistance, and left ventricular work tended to decrease as anesthesia deepened. We found no significant difference in cardiovascular measurements in dogs between spontaneous and controlled ventilation at equal MAC multiples. That isoflurane is a profound respiratory depressant in dogs and cats is supported by our findings of a dose-dependent increase in PaCO2. In addition, the alveolar isoflurane concentration required to produce at least 60 seconds of apnea divided by MAC (i.e., the anesthetic index) averaged 2.5 for dogs and 2.4 for cats. The anesthetic index which we determined for isoflurane in dogs equals or is less than the index reported for other inhaled anesthetics in this species.     

Ultrasound-guided 1.2-mm cutting-needle biopsies of head and neck tumours

BACKGROUND: The direct effect of halothane on vascular smooth muscle is mediated in part via its effects on the sarcoplasmic reticulum (SR). Little information is available concerning the effects of other volatile anesthetics including isoflurane and sevoflurane, whose vascular effects differ from those of halothane. The aim of the present study was to compare the effects of halothane, isoflurane and sevoflurane on the SR by testing the contraction induced by caffeine in vascular smooth muscle. METHODS: Rings without endothelium from isolated canine mesenteric artery were mounted in physiological saline solution (PSS) for isometric tension recording. After complete depletion of Ca2+ from the SR by adding 35 mM caffeine, the rings were exposed to normal Ca2+ containing PSS (Ca2+ loading), to Ca(2+)-free PSS for 10 min, and then to 15 mM caffeine to induce contraction. Anesthetics were administered during Ca2+ loading, the Ca(2+)-free phase and simultaneously with caffeine administration. RESULTS: Halothane (0.5-2%) attenuated the caffeine-induced contraction of canine mesenteric artery when administered during Ca2+ loading in the SR (P < 0.001), whereas isoflurane and sevoflurane (1-4%) failed to affect the contraction. When given simultaneously with caffeine, halothane (1-2%) potentiated the caffeine-induced contraction (P < 0.05), but isoflurane and sevoflurane had no effect. When given before caffeine administration, halothane (0.5-2%), isoflurane (2-4%) and sevoflurane (4%) all potentiated the caffeine-induced contraction (P < 0.05). CONCLUSION: It has been shown that halothane not only potentiates caffeine-induced Ca2+ release from the SR, but also induces contraction by releasing Ca2+ from the SR. We conclude that halothane decreases Ca2+ accumulation in the SR while exerting facilitative and additive effects on caffeine-induced Ca2+ release from the SR when applied before caffeine administration and simultaneously with caffeine, respectively, whereas isoflurane and sevoflurane lack both the ability to decrease Ca2+ accumulation and an additive effect on caffeine-induced Ca2+ release from the SR, but are able to facilitate Ca2+ release by caffeine.