Biomedical subjects

E I Eger

Publications and source records attributed to E I Eger.

At least 19 recordsLinked to original sources

PubMed1992

Elderly, conscious patients have an accentuated hypotensive response to nitroglycerin.

There is no adequate explanation for the highly variable response of systemic blood pressure to nitroglycerin (glyceryl trinitrate [GTN]). Aging produces cardiovascular changes that should alter the effects of GTN, but elderly patients usually have been excluded from studies of GTN. Accordingly, the authors compared the effects of GTN on systemic blood pressure in elderly and younger patients. Fifty-three patients, aged 49-87 (with 30 patients older than 70), were studied. Before elective vascular surgery, 14 patients received an infusion of placebo; 26, a constant infusion of GTN; and 13, a stepwise increasing infusion of GTN. After a standardized anesthetic induction and the start of surgery, the identical infusion protocols were repeated in each group. Data on GTN infusion rate, arterial blood pressure, and GTN concentrations versus time, age, and other potentially influencing variables were pooled for analysis. Before anesthesia and surgery, GTN more commonly caused excessive hypotension in patients older than 70 yr than in younger patients, but none of the patients had complications. A repeated-measures model analysis indicated that age significantly influenced the effects of GTN on blood pressure. That is, patients who are in their 70s who receive 0.5 micrograms.kg-1.min-1 of GTN are predicted to experience a twofold greater decrease in systolic arterial pressure (approximately 33 mmHg) than patients in their 50s. However, no apparent effect of age on intraoperative GTN responsiveness was discernible nor was a predictable relationship found between the preoperative and intraoperative responsiveness or between arterial concentrations of GTN and blood pressure or age. Therefore, the authors conclude that, in the absence of the effects of anesthesia and surgery, elderly patients have a more pronounced blood pressure response to GTN than younger patients. Furthermore, the authors conclude that preoperative blood pressure responsiveness to GTN is not a reliable predictor of intraoperative responsiveness.

Aged↗

PubMed1992

Effects of isoflurane and nitrous oxide in subanesthetic concentrations on memory and responsiveness in volunteers.

Awareness, defined as conscious memory during anesthesia, has been a problem in anesthesia practice. To determine the effect of isoflurane and nitrous oxide (N2O) on memory, 17 healthy adult volunteers were randomly assigned to receive isoflurane or N2O and received the alternate agent 1-2 weeks later. Each volunteer was studied at four end-tidal concentrations of each agent, consecutively 0.15, 0.3, 0.45, and 0.15 times the minimum alveolar concentration (MAC) for isoflurane or 0.3, 0.45, 0.6, and 0.3 times MAC for N2O. After 15-min equilibration at each end-tidal concentration, volunteers were tested for voluntary response to command and were presented with verbal information to be recalled after anesthesia. Volunteers were interviewed on the day after the study and tested for conscious and unconscious memory of the information presented during anesthetic administration. MAC-awake (the end-tidal concentration preventing voluntary response in 50% of volunteers) was 0.38 (0.35-0.42) times MAC for isoflurane and 0.64 (0.61-0.68) MAC for N2O (means, 95% confidence limits), indicating isoflurane to be more potent than N2O in suppressing voluntary response (P = .0001). Memory data were analyzed in 12 volunteers who completed the study and in whom the allocation of information to be recalled was counterbalanced among agents and concentrations of agents. Memory was decreased by increasing concentrations of both agents. Conscious memory of the information presented during anesthetic administration was prevented by 0.45 MAC isoflurane but not completely prevented by 0.6 MAC N2O. Unconscious memory (defined as memory of information without conscious recognition) occurred during administration of both agents and was prevented by 0.45 MAC isoflurane but not by 0.6 MAC N2O. Isoflurane was more potent in suppressing memory than MAC-equivalent concentrations of N2O. Using models of the relationship between dose of agent and suppression of memory, a dose of both agents was estimated that suppressed memory by 50% (ED50). The ED50 was 0.20 MAC for isoflurane (95% confidence intervals, 0.15-0.25), and 0.50 MAC for N2O (95% confidence intervals 0.43-0.55). We conclude that isoflurane and N2O suppress memory in a dose-dependent manner, and that isoflurane is more potent in preventing memory and voluntary response to command than MAC-equivalent concentrations of N2O.

Adolescent↗

PubMed1992

Desflurane does not produce hepatic or renal injury in human volunteers.

We examined the potential toxicity of desflurane in 13 young 25.0 +/- 2.3 (mean +/- SD) yr-old men, given 7.35 +/- 0.81 MAC-hours of desflurane anesthesia. Hepatic and renal function tests, serum electrolytes, and standard urine and hematologic tests were performed before, during, and after anesthesia. No toxicity was found. There were no changes in tests of hepatocellular integrity (plasma alanine transferase activity), synthetic function (serum albumin, prothrombin time, partial thromboplastin time), or renal function (serum creatinine concentration, blood urea nitrogen concentration). Decreases in red blood cell count, hematocrit, and blood hemoglobin concentration during and immediately after anesthesia were attributed to blood sampling and infusion of intravenous electrolyte solution. These values returned by 4 days after anesthesia to values not different from those before anesthesia. Increased white blood cell counts and blood glucose concentrations noted during anesthesia with other inhaled anesthetics were also seen in these volunteers. Desflurane appears to have no greater toxicity than currently used inhaled anesthetics and, because of its lesser metabolism, may have lesser or not toxicity.

Adult↗

PubMed1992

Isoflurane anesthesia prevents unconscious learning.

We investigated whether greater than or equal to 0.6 minimum alveolar concentration (MAC) of isoflurane suppresses learning of information presented verbally. Preoperatively, we asked 45 healthy patients (aged 23-58 yr) undergoing elective surgery 15 general knowledge questions designed to arouse their curiosity. They were told that they would be given the answers during anesthesia. Anesthesia was induced with isoflurane and nitrous oxide (25 subjects also received 1.1 +/- 0.6 mg/kg of propofol). The trachea was intubated with the aid of vecuronium (0.07 mg/kg IV). Isoflurane in oxygen was given to provide 0.6 MAC before and 1.0 and 1.4 MAC during surgery. After 10 min at each of two of the three MAC levels, the answers were given to five of the questions. At the remaining concentration, patients received a message to either touch an ear (n = 30) or keep their arms still (n = 15) during the postoperative interview. Twenty-four hours later, patients were asked whether they recalled intraoperative events. They were then asked to answer the 15 questions, choosing from five possible answers to each, one of which was correct. The number of times each patient touched an ear during this interview was noted. No patient consciously recalled events during anesthesia. The number of questions answered correctly postoperatively did not differ according to whether the answers had been provided during anesthesia (at any isoflurane concentration) or had not been provided (control questions). The number of ear-touches postoperatively did not differ between those who had and had not received the intraoperative message encouraging ear-touching.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Desflurane animal and human pharmacology: aspects of kinetics, safety, and MAC.

Substitution of fluorine for the single chlorine atom in isoflurane produces the new anesthetic, desflurane. This seemingly small change produces several pharmacologic changes. The potency of desflurane (MAC equals 6.0% in middle-aged patients) is one-fifth that of isoflurane (1.15%), with MAC for each agent decreased by aging, hypothermia, or the addition of depressants such as midazolam, fentanyl, or nitrous oxide. Some properties are similar: desflurane and isoflurane both depress respiration and neuromuscular contractility, and higher concentrations (e.g., 6%-8% desflurane) of both agents have a pungency that can provoke breath holding, laryngospasm, and salivation, particularly in infants and children. Of great importance, the substitution of fluorine for chlorine markedly decreases blood (desflurane blood-gas partition coefficient 0.42) and tissue solubility (e.g., brain-blood partition coefficient 1.3) relative to isoflurane (values 1.4 and 1.6, respectively). As a result, desflurane alveolar concentrations may be adjusted more rapidly and precisely; desflurane enters and leaves the lungs and tissues more rapidly; and recovery is quicker both for the short (first 10-20 min) and long (0.5-1.5 h) term. This greater precision of control and more rapid recovery are consistent with trends for new drug development in anesthesiology.

Anesthesia, Inhalation↗

PubMed1991

The neuromuscular effects of desflurane, alone and combined with pancuronium or succinylcholine in humans.

The neuromuscular effects of desflurane administered alone were studied in ten healthy human volunteers aged 20-27 yr. Also, the dose-response relationships of pancuronium and succinylcholine in surgical patients during anesthesia with desflurane (n = 13) were compared to those during isoflurane anesthesia (n = 14). In the volunteers, we measured the mechanical response of the adductor pollicis muscle to stimulation of the ulnar nerve in a train-of-four (TOF) sequence at 2 Hz and at tetanic frequencies of 50, 100, and 200 Hz, each administered for 5 s. Amplitudes of the first response (T1) in each TOF sequence and the ratios of the fourth TOF response (T4) to the first were similar at 3, 6, and 9% desflurane and decreased significantly only at 12% (P less than 0.05). Desflurane concentrations of 3-12% caused tetanic fade (greater than 10% decrement in amplitude) at 50, 100, and 200 Hz. The addition of N2O and the duration of anesthetic exposure did not alter desflurane's neuromuscular effects. The only neuromuscular variable influenced by CO2 was T1 amplitude, which decreased as arterial CO2 tension (PaCO2) increased. The doses of pancuronium that depressed T1 amplitude by 50% (ED50) were similar during anesthesia with 1.25 MAC desflurane, 10.5 +/- 2.8 micrograms/kg (mean +/- SD) and 1.25 MAC isoflurane, 12.3 +/- 5.0 micrograms/kg. The ED50 doses of succinylcholine were similar during anesthesia with desflurane 132 +/- 76 micrograms/kg and isoflurane 123 +/- 36 micrograms/kg. We conclude that desflurane significantly depresses neuromuscular function and augments the action of pancuronium and succinylcholine to a degree similar to that of isoflurane.

Adult↗

PubMed1991

Clinical characteristics of desflurane in surgical patients: minimum alveolar concentration.

Desflurane (formerly I-653) is a new inhalaticnal anesthetic with a promising pharmacokinetic profile that includes low solubility in blood and tissue, including fat. Since its lipid solubility is less than that of other volatile agents, it may have lower potency. Low solubility would be expected to increase the rate at which alveolar concentration approaches inspired concentration during induction as well as to increase the rate of elimination of desflurane from blood at emergence. We determined the minimum alveolar concentration (MAC) of desflurane in 44 unpremedicated ASA physical status 1 or 2 patients undergoing elective surgery. We prospectively studied four patient groups distinguished by age and anesthetic regimen: 18-30 versus 31-65 yr and desflurane in 60% N2O/40% O2 versus desflurane in O2. Anesthesia was induced with desflurane or desflurane in 60% N2O/40% O2. MAC was determined by a modification of Dixon's up-and-down method with increments of 0.5% desflurane. The MAC of desflurane in O2 was 7.25 +/- 0.0 (mean +/- SD) in the 18-30-yr age group, and 6.0 +/- 0.29 in the 31-65-yr group; the addition of 60% N2O reduced the MAC to 4.0 +/- 0.29 and 2.83 +/- 0.58, respectively. The median time from discontinuation of desflurane to an appropriate response to commands was 5.25 min. Desflurane appears to be a mild airway irritant but was well tolerated by all patients.

Adult↗

PubMed1991

The electroencephalographic effects of desflurane in humans.

The electroencephalographic (EEG) effects of a new inhaled anesthetic are of interest because of the potential of such agents to produce excitatory (convulsant) activity and because of the potential usefulness of the EEG as an indicator of anesthetic depth and cerebral activity. Accordingly, we examined the EEG in 12 healthy, young male volunteers during desflurane anesthesia. Each subject had a baseline recording and then steady-state exposure to 6, 9, and 12% (0.83, 1.24, and 1.66 MAC) desflurane in O2 alone, and to 3, 6, and 9% desflurane in O2 with 60% N2O. The sequence of doses and the presence of N2O were randomized. We used mechanical ventilation to maintain normocapnia at each dose level. We also tested the effects of hypercapnia secondary to spontaneous ventilation. Additionally, at 1.24 MAC, subjects' lungs were hyperventilated to a PCO2 of 25.8 +/- 0.7 mmHg and exposed to rhythmic, loud clapping to attempt to provoke excitatory phenomena. Finally, after at least 6 h exposure to desflurane, we repeated measurements at 0.83 and 1.66 MAC to assess possible tolerance. Four channels of EEG were monitored visually, and at each dose, a quantitative EEG analysis was performed. Desflurane produced EEG changes comparable to those observed with equipotent levels of isoflurane. No epileptiform activity was seen. Desflurane significantly suppressed EEG activity; prominent burst suppression was seen at 1.24 MAC and higher. Substitution of N2O for 0.42 MAC desflurane reduced the degree of EEG suppression relative to the equipotent administration of desflurane and O2. Quantitative EEG measures for the early doses and for the later, repeated exposures did not differ.

Adult↗

PubMed1991

Percutaneous loss of desflurane, isoflurane, and halothane in humans.

We studied the percutaneous losses of the new inhaled anesthetic, desflurane (I-653), and of isoflurane and halothane during anesthetic administration and elimination in seven healthy male volunteers. Anesthesia was induced and maintained with midazolam, thiopental, and fentanyl. We administered 70% N2O for 30 min, and then administered 2% desflurane, 0.4% isoflurane, and 0.2% halothane concurrently with 65% N2O for 30 min. Inspired, end-tidal, and mixed-expired gas samples were collected during administration of the volatile agents and for 5-7 days of elimination. The right arm and hand of each subject was enclosed in a sealed glass cylinder having a port at each end, one for sampling and both for flushing with N2 after anesthetic administration and every 15 min thereafter. We sampled gases from the cylinder during administration and for the 150 min of elimination and analyzed their anesthetic concentrations by gas chromatography. The surface area of the enclosed portion of the arm was measured, and the total body surface area was calculated. All values were normalized to (i.e., divided by) the end-tidal (alveolar) concentration at the end of administration. During administration, percutaneous loss of halothane was 3.5 times that of desflurane and 2 times that of isoflurane. During elimination, the loss of halothane was 6 times and 2 times greater than the loss of desflurane and isoflurane, respectively. Percutaneous loss of halothane significantly exceeded that of isoflurane. The elimination values included an estimate of elimination after 150 min. The percutaneous loss of each anesthetic was 2- to 3-fold greater during elimination than administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Depression of ventilation by desflurane in humans.

We studied the ventilatory effects of desflurane (formerly I-653) with and without N2O in healthy male volunteers. After insertion of venous and arterial (radial and pulmonary) catheters, baseline measurements of tidal volume (VT), respiratory rate (RR), ventilatory response to CO2, and arterial and mixed venous blood gases were made. Subjects were randomly assigned to receive either desflurane with O2 (n = 6) or with O2 and 60% N2O (n = 6). Anesthesia was induced by inhalation of desflurane followed by tracheal intubation without muscle relaxants. In each volunteer, at end-tidal concentrations totaling 0.83, 1.24, and 1.66 MAC, we repeated measurements of VT, RR, response to CO2, and arterial and mixed venous blood gases. As depth of anesthesia increased, VT significantly (P less than 0.05) decreased from 363 +/- 22 ml awake to 76 +/- 22 ml at 1.66 MAC without N2O and from 473 +/- 70 ml awake to 128 +/- 6 ml at 1.66 MAC with N2O (mean +/- SE). Similarly, RR increased from 15 +/- 0.5 breaths per min awake to 32 +/- 2 breaths per min at 1.66 MAC without N2O and from 14 +/- 0.5 breaths per min awake to 40 +/- 3 breaths per min at 1.66 MAC with N2O. Desflurane without N2O depressed the ventilatory response to CO2 to 45 +/- 9, 31 +/- 5, and 11 +/- 4% of the awake values at 0.83, 1.24, and 1.66 MAC, respectively. With N2O, values were 52 +/- 14, 23 +/- 5, and 26 +/- 9% of the awake value at 0.83, 1.24, and 1.66 MAC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Kinetics of desflurane, isoflurane, and halothane in humans.

The low solubility of desflurane in blood and tissues suggests that the partial pressures of this agent in blood and tissues should approach the inspired partial pressure more rapidly than would the blood and tissue partial pressures of other potent inhaled anesthetics. We tested this prediction, comparing the pharmacokinetics of desflurane with those of isoflurane, halothane, and nitrous oxide in eight volunteers. We measured the rate at which the alveolar (endtidal) (FA) concentration of nitrous oxide increased towards an inspired (FI) concentration of 65-70%, and then measured the concurrent increase in FA and mixed expired concentrations (FM) of desflurane, isoflurane, and halothane at respective FI values of 2.0%, 0.4%, 0.2%. Minute ventilation (VE) was measured concurrently with the measurements of anesthetic concentrations. The potent vapors were administered for 30 min; administration of nitrous oxide continued throughout the period of anesthesia. For the potent agents, we also measured VE, FA, and FM for 5-7 days of elimination. We used FA/FI and FA/FA0 (FA0 = the last FA during the administration of each anesthetic) to define the rate of increase of anesthetic in the lungs and the rate of elimination of anesthetic, respectively. FA/FI values at 30 min of administration were: (mean +/- SD) nitrous oxide 0.99 +/- 0.01, desflurane 0.90 +/- 0.01, isoflurane 0.73 +/- 0.03, and halothane 0.58 +/- 0.04. FA/FA0 values after 5 min of elimination were: desflurane 0.14 +/- 0.02, isoflurane 0.22 +/- 0.02, and halothane 0.25 +/- 0.02. Recovery (volume of anesthetic recovered during elimination per volume taken up) of desflurane (105 +/- 25%) equalled recovery of isoflurane (102 +/- 13%) and exceeded recovery of halothane (64 +/- 9%). Time constants for a five-compartment mammillary model for halothane and isoflurane differed for the lungs, fat group, and hepatic metabolism, and exceeded those for desflurane for all compartments. In summary, we found that FA/FI of desflurane increases more rapidly and that FA/FA0 decreases more rapidly in humans than do these variables with other available potent anesthetics. We also found that desflurane resists biodegradation in humans and so may have little or no toxic potential.

Adult↗

PubMed1991

Cerebral uptake and elimination of desflurane, isoflurane, and halothane from rabbit brain: an in vivo NMR study.

The authors used in vivo 19F nuclear magnetic resonance spectroscopy to determine rates of cerebral uptake and elimination of desflurane, isoflurane, and halothane in rabbits. After anesthetizing animals by intramuscular and intravenous injection of methohexital and inhalation of 70% nitrous oxide, intravenous and intraarterial catheters were inserted and a tracheostomy and craniotomy performed. Ventilation was controlled to maintain arterial carbon dioxide tension (PaCO2) from between 35 and 45 mmHg. A 2-2.5-cm diameter circle of dura was exposed, over which a 0.9 x 1.0-cm elliptical surface coil was placed. Cerebral anesthetic concentrations (CC) were estimated from spectra acquired on a 4.7-Tesla spectrometer. Alveolar uptake and elimination also were assessed, using inspired (FI) and end-tidal (denoted FA0 at the end of administration) concentrations measured by gas chromatography. After baseline spectra were obtained, volatile agents were administered for 30 min, followed by a 120-min period of elimination. Our findings demonstrate that cerebral uptake and elimination correlate with solubility: they are most rapid for desflurane, next most rapid for isoflurane, and least rapid for halothane. During administration, cerebral uptake of desflurane (CC/FI = 0.690 +/- 0.049 at 9 min) was approximately 1.7 times faster than isoflurane (CC/FI = 0.691 +/- 0.020 at 15 min) and 3 times faster than halothane (CC/FI = 0.662 +/- 0.040 at 27 min). Similarly, elimination rates for desflurane (CC/FA0 = 0.238 +/- 0.015 at 9 min) were 1.7 times faster than isoflurane (CC/FA0 = 0.236 +/- 0.017 at 15 min) and three times faster than halothane (CC/FA0 = 0.212 +/- 0.033 at 27 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

No EEG evidence of acute tolerance to desflurane in swine.

Desflurane is a potent inhaled anesthetic associated with a dose-dependent depression of cortical electrical activity. Recently, it has been suggested that the burst suppression pattern seen in dogs given moderately high doses (2.0 MAC) of desflurane may spontaneously subside. This observation suggests the development of acute tolerance to at least some of the anesthetic effects of this drug. No other volatile anesthetic has been found to produce acute tolerance. We attempted to replicate these findings in domestic swine. Five juvenile swine (25-30 kg) were anesthetized with desflurane in oxygen and during normocapnia were exposed to two doses of desflurane sufficient to induce burst suppression (1.5 and 1.7 MAC) for 35 min at each dose, with a period of EEG recovery (0.6 MAC) before, between (in 3 of 5 animals), and after the high doses. Frontoparietal EEG was continuously recorded and the burst suppression ratio continuously calculated. Suppression was more complete at 1.7 MAC than at 1.5 MAC (98.24 +/- 1.75 vs. 90.80 +/- 3.05%, respectively, mean +/- standard deviation). The degree of burst suppression activity did not change over time at either 1.5 (P greater than 0.33) or 1.7 MAC desflurane (P greater than 0.41). There was no EEG evidence of tolerance to desflurane anesthesia in swine.

Anesthesia, Inhalation↗

PubMed1991

Comparison of percutaneous losses of sevoflurane and isoflurane in humans.

We studied the percutaneous losses of sevoflurane and isoflurane during administration and elimination in seven healthy male volunteers. Anesthesia was induced and maintained with fentanyl, midazolam, and/or thiopental, and nitrous oxide for 30 min, after which 1% sevoflurane and 0.4% isoflurane in 65% nitrous oxide were administered for 30 min. Inspired, end-tidal, and mixed-expired gas samples were collected during administration and for 5-7 days of elimination. To measure percutaneous loss, each subject's arm was enclosed in a glass cylinder sealed at both ends and with two ports, one for flushing with nitrogen and one for obtaining gas samples during the 30 min of administration and the first 150 min of elimination. Anesthetic concentrations in all samples were determined using gas chromatography. The surface area of the arm was measured and the total surface area was calculated. During administration and elimination, percutaneous loss of isoflurane was significantly greater than that of sevoflurane (P less than 0.05). For both volatile agents, losses during elimination were greater than during administration (P less than 0.05), but even when combined, these losses were too small to affect kinetic or metabolic studies based on mass balance.

Adult↗

PubMed1991

Comparison of kinetics of sevoflurane and isoflurane in humans.

The low solubility of sevoflurane in blood suggests that this agent should enter and leave the body more rapidly than isoflurane. However, the closeness of sevoflurane and isoflurane tissue/blood partition coefficients suggests that the rates of equilibration with and elimination from tissues should be similar. We tested both predictions, comparing sevoflurane with isoflurane and nitrous oxide in seven volunteers. We measured the rate at which the alveolar (end-tidal) (FA) concentration of nitrous oxide increased toward an inspired (FI) concentration of 65%-70%, then measured the concurrent rise in FA and mixed expired concentrations (FM) of sevoflurane and isoflurane at respective FI values of 1.0% sevoflurane and 0.6% isoflurane for 30 min. Minute ventilation (VE) was measured concurrently with the measurements of anesthetic concentrations. For the potent agents, we also measured VE, FA, and FM for 6-7 days of elimination. FA/FI values at 30 min of administration were as follows: nitrous oxide, 0.986 +/- 0.003 (mean +/- SD); sevoflurane, 0.850 +/- 0.018; and isoflurane, 0.733 +/- 0.027. FA/FA0 (FA0 = the last FA during administration) values after 5 min of elimination were as follows: sevoflurane, 0.157 +/- 0.020; isoflurane, 0.223 +/- 0.024. Recovery (volume of anesthetic recovered during elimination/volume taken up) of sevoflurane (101% +/- 7%) equaled recovery of isoflurane (101% +/- 6%). Time constants for a five-compartment mammillary model for sevoflurane were smaller than those for isoflurane for the lungs but were not different from isoflurane for the other compartments.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1991

What solvent best represents the site of action of inhaled anesthetics in humans, rats, and dogs?

The correlation between the potency of inhaled anesthetics and their solubility in a hydrophobic phase provides an opportunity to define better the characteristics of the anesthetic site of action. The correlation implies that inhaled anesthetics act in a hydrophobic site and that the solvent used has properties representative of the true site of anesthetic action. We sought to characterize this site more accurately by testing for the solvent that provided the best correlation for a diverse group of anesthetics. We determined the solubility of halothane, enflurane, cyclopropane, fluroxene, isoflurane, sevoflurane, and desflurane in benzene, olive oil, Intralipid, n-octanol, and lecithin. We used established MAC values for rats, dogs, and humans for all but sevoflurane and desflurane, for which we determined MAC in rats to be 2.80% +/- 0.24% (mean +/- standard deviation) and 7.71% +/- 0.65%, respectively. Lecithin gave the lowest coefficient of variation for the product of potency (MAC) x solubility, but the difference was statistically significant only for a comparison of the products for lecithin and olive oil. The values for lecithin were within the range of values produced by biological variation. More important, the correlation of log MAC and log solubility had an average slope of unity (-1.04 +/- 0.07) for lecithin, but a slope differing from unity for benzene (-0.82 +/- 0.05) and olive oil (-0.87 +/- 0.05). We conclude that lecithin is probably more representative of the site of action of these anesthetics than the other solvents.

Anesthesia, Inhalation↗

PubMed1991

Absorption and degradation of sevoflurane and isoflurane in a conventional anesthetic circuit.

Soda lime and Baralyme degrade sevoflurane, the rate of degradation being a direct function of temperature. We tested whether this degradation would impede the development of an anesthetizing concentration of sevoflurane (compared with isoflurane, a compound that is not degraded) in a circle-absorption system having an increased temperature consequent to (a) carbon dioxide production (200 mL/min) and absorption; and (b) a low inflow rate (70 mL/min). We also measured the temperatures reached in various parts of the absorption system when used in clinical practice, finding that peak temperatures usually reached 37 degrees - 46 degrees C when low inflow rates (500 mL/min) were applied. The tests in the model system demonstrated that soda lime and Baralyme absorbed both sevoflurane and isoflurane, and that both absorbants degraded sevoflurane but not isoflurane. Baralyme produced a fourfold greater degradation of sevoflurane vapor than did soda lime (0.66 mL/min compared with 0.17 mL/min). However, except for a slight delay at the start of anesthesia, neither absorption nor degradation should noticeably affect the requirement for anesthetic delivery in clinical practice, even in low-flow systems.

Absorption↗

PubMed1991

Hemodynamic effects of desflurane/nitrous oxide anesthesia in volunteers.

We determined the cardiovascular effects of 0.91, 1.34, and 1.74 MAC of desflurane/nitrous oxide anesthesia (60% inspired nitrous oxide contributed 0.5 MAC at each level) in 12 healthy, normocapnic male volunteers. Desflurane/nitrous oxide anesthesia decreased systemic blood pressures, cardiac index, stroke volume index, systemic vascular resistance, and left ventricular stroke work index, and increased pulmonary arterial pressures and central venous pressure in a dose-dependent fashion, while heart rate was 10%-12% and mixed venous oxygen tension was 2-4 mm Hg higher at all MAC levels than at baseline (awake). Desflurane/nitrous oxide anesthesia modestly increased left ventricular end-diastolic cross-sectional area (preload) and decreased velocity of left ventricular circumferential fiber shortening, systolic wall stress (afterload), and area ejection fraction; this combination of changes indicates myocardial depression. At approximately comparable MAC levels, heart rate was lower and systemic blood pressures, central venous pressure, left ventricular stroke work index, and systemic vascular resistance usually were significantly higher during anesthesia with desflurane and nitrous oxide than during desflurane anesthesia alone (same volunteers, data collected in crossover design). After 7 h of anesthesia, regardless of the background gas, somewhat less cardiovascular depression and/or modest stimulation was apparent: cardiac index, area ejection fraction, and velocity of left ventricular circumferential fiber shortening recovered to or toward awake values, whereas heart rate was further increased. Evidence of circulatory insufficiency did not develop in any volunteers during the study. Segmental left ventricular function was normal at baseline, and no segmental wall-motion abnormalities, ST-segment change, or dysrhythmias developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗