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Edmond I Eger

Publications and source records attributed to Edmond I Eger.

At least 37 records · Page 2Linked to original sources
PubMed2005

Solubility of volatile anesthetics in bovine white matter, cortical gray matter, thalamus, hippocampus, and hypothalamic area.

Although known for whole brain, values are lacking for solubilities of modern volatile anesthetics in specific brain regions. Some regions should differ from others (e.g., gray matter versus white matter) because they differ in lipid content and because potent inhaled anesthetics are lipophilic. In the present report, we examined this issue in bovine brain, finding that white matter/gas partition coefficients are 1.6 (desflurane) to 2.4 (halothane) times larger than gray matter/gas partition coefficients, with values for isoflurane and sevoflurane lying between these at 1.9. Values for thalamus/gas, hypothalamic area/gas, and hippocampal/gas partition coefficients lie between those for gray and white matter. These data may be useful in defining the parts of the brain involved with return to consciousness during recovery from anesthesia.

Algorithms↗
PubMed2005

Illustrations of inhaled anesthetic uptake, including intertissue diffusion to and from fat.

Although several mathematical and computer simulations of inhaled anesthetic pharmacokinetics have been devised, their complexity sometimes limits an intuitive appreciation of the interactions produced by the determinants of kinetics. In this essay, we illustrate the factors that govern inhaled anesthetic pharmacokinetics with drawings that consider delivery of anesthetic by ventilation to the lungs and dispersion of the anesthetic to tissue depots by the circulation. The illustrations incorporate the effects of both blood flow and blood solubility as determinants of the extent of dispersion. They incorporate tissue volume and solubility as determinants of the capacity of the tissue depots. Capacity to hold (take up) anesthetic is depicted by areas representing specific tissues, and the extent of anesthetic movement is depicted by the length and breadth of arrows to and from the areas depicting capacity. The illustrations incorporate increasingly important elements to kinetics, such as obesity. Obesity increases the depots available for storage of anesthetic, including anesthetic that reaches fat by intertissue diffusion. Such anesthetic returns to the circulation to delay recovery in healthy and obese patients, particularly with more soluble anesthetics. However, the increased anesthetic in fat occurs at a lower partial pressure and thus might not influence emergence materially. We hope that these illustrations will allow anesthesia practitioners to appreciate the interactions of the factors that govern inhaled anesthetic pharmacokinetics.

Adipose Tissue↗
PubMed2005

Administration of epinephrine does not increase learning of fear to tone in rats anesthetized with isoflurane or desflurane.

Previous reports suggest that the administration of epinephrine increases learning during deep barbiturate-chloral hydrate anesthesia in rats but not during anesthesia with 0.4% isoflurane in rabbits. We revisited this issue, using fear conditioning to a tone in rats as our experimental model for learning and memory and isoflurane and desflurane as our anesthetics. Expressed as a fraction of the minimum alveolar anesthetic concentration (MAC) preventing movement in 50% of rats, the amnestic 50% effective dose (ED(50)) for fear to tone in control rats inhaling isoflurane and injected with saline intraperitoneally (i.p.) was 0.32 +/- 0.03 MAC (mean +/- se) compared with 0.37 +/- 0.06 MAC in rats injected with 0.01 mg/kg of epinephrine i.p. and 0.38 +/- 0.03 MAC in rats injected with 0.1 mg/kg of epinephrine i.p. For desflurane, the amnestic ED(50) were 0.32 +/- 0.05 MAC in control rats receiving a saline injection i.p. versus 0.36 +/- 0.04 MAC in rats injected with 0.1 mg/kg of epinephrine i.p. We conclude that exogenous epinephrine does not decrease amnesia produced by inhaled isoflurane or desflurane, as assessed by fear conditioning to a tone in rats.

Anesthesia, Inhalation↗
PubMed2005

The effect of three inhaled anesthetics in mice harboring mutations in the GluR6 (kainate) receptor gene.

Combinations of GluR5-GluR7, KA1, and KA2 subunits form kainate receptors, a subtype of excitatory ionotropic glutamate receptors. Isoflurane enhances the action of kainate receptors comprising GluR6 subunits expressed in oocytes. To test whether alterations of the GluR6 subunit gene affect the actions of inhaled anesthetics in vivo, we measured the minimum alveolar concentration of desflurane, isoflurane, and halothane in mice lacking the kainate receptor subunit GluR6 (GluR6 knockout mice) and mice with a dominant negative glutamine/arginine (Q/R) editing mutation in membrane domain 2 of the GluR6 receptor (GluR6 editing mutants), which increases the calcium permeability of kainate receptors containing GluR6Q. We also measured the capacity of isoflurane to interfere with Pavlovian fear conditioning to a tone and to context. Absence of the GluR6 subunit did not change the minimum alveolar concentration of isoflurane, desflurane, or halothane. Possibly, kainate receptors assembled from the remaining kainate receptor subunits compensate for the absent subunits and thereby produce a normal minimum alveolar concentration. A Q/R mutation that dominantly affects kainate receptors containing the GluR6 subunit in mice increased isoflurane minimum alveolar concentration (by 12%; P < 0.01), decreased desflurane minimum alveolar concentration (by 18%; P < 0.001), and did not change halothane minimum alveolar concentration (P = 0.25). These data may indicate that kainate receptors containing GluR6Q subunits differently modulate, directly or indirectly, the mechanism by which inhaled anesthetics cause immobility. The mutations of GluR6 that were studied did not affect the capacity of isoflurane to interfere with fear conditioning.

Anesthetics, Inhalation↗
PubMed2005

R (+) etomidate and the photoactivable R (+) azietomidate have comparable anesthetic activity in wild-type mice and comparably decreased activity in mice with a N265M point mutation in the gamma-aminobutyric acid receptor beta3 subunit.

A photoactivable diazirine derivative of etomidate, azietomidate, shares many actions of etomidate, including a capacity to abolish the righting reflexes in tadpoles and enhance gamma-aminobutyric acid (GABA)-induced currents. Azietomidate's usefulness in studies of mechanisms of anesthesia depends on the assumption that it shares a site of action with etomidate. Mice bearing an N265M beta3 subunit point mutation in GABA(A) receptors have a markedly decreased sensitivity to loss of righting reflexes induced by etomidate over a range of doses. Accordingly, in the present study we measured the time to recovery of righting reflexes of wild type and mutant mice as a function of dose given as an IV bolus. Analysis of the data for azietomidate yielded mean times to recovery of righting reflexes at a dose of 7.5 mg/kg of 10.0 +/- 0.9 min and 3.0 +/- 1.6 min for wild type and mutant mice, respectively (mean +/- sd). A similar analysis for etomidate yielded mean times to recovery of righting reflexes at a dose of 7.5 mg/kg of 12.0 +/- 1.3 min and 4.0 +/- 0.7 min for wild type and mutant mice respectively. Thus, at this dose a single mutation, N265M on the beta3 subunit of the GABA(A) receptor, approximately halved the time to recovery of righting reflexes for both etomidate and azietomidate (by 7.6 +/- 1.5 min and 7.2 +/- 1.8 min, respectively), emphasizing the contribution of this residue as a determinant of a behavioral response of azietomidate in mice.

Anesthetics, Intravenous↗
PubMed2005

Beta3-containing gamma-aminobutyric acidA receptors are not major targets for the amnesic and immobilizing actions of isoflurane.

UNLABELLED: Mice bearing an N265M point mutation in the gamma-aminobutyric acid (GABA)(A) receptor beta3 subunit resist various anesthetic effects of propofol and etomidate. They also require a 16% larger concentration of enflurane and a 21% larger concentration of halothane to abolish the withdrawal reflex than do wild-type mice. Using a Pavlovian test, we measured whether this mutation increased the concentration of isoflurane required to impair learning and memory relative to wild-type mice. We found that the concentration was not significantly increased. We also measured MAC (the minimum alveolar concentration required to eliminate movement in response to noxious stimulation in 50% of subjects). Isoflurane MAC for mutant mice (1.93% +/- 0.0.03%; mean +/- se; n = 14) was 17.0% larger than MAC for wild-type mice (1.65 +/- 0.04; n = 14; P < 0.001). Similarly, the cyclopropane MAC for mutant mice (27.6% +/- 0.55%; n = 16) was 13.6% larger than MAC for wild-type mice (24.3 +/- 0.46; n = 8; P < 0.01). The increase in MAC for cyclopropane was unexpected, because published reports find only minimal actions at alpha1beta2gamma2 GABA(A) receptors whereas isoflurane provides a large enhancement. Consistent with previous work on alpha1beta2gamma2 GABA(A) receptors, we found in Xenopus oocytes that 5 MAC cyclopropane enhanced the effect of GABA on alpha1beta2gamma2 GABA(A) receptors by only 76%, and by a nearly identical enhancement in alpha1beta3gamma2, and alpha6beta3gamma2 receptors. In contrast, a much smaller concentration of isoflurane (1 MAC) produced a 160% to 310% enhancement in these receptors. If, relative to isoflurane, cyclopropane minimally increases GABA-induced chloride currents at any GABA(A) receptor subtype, the present data for MAC are consistent with the notion that GABA(A) receptors do not mediate the immobility produced by inhaled anesthetics. IMPLICATIONS: The results of the present study indicate that beta3-containing gamma-aminobutyric acidA receptors do not mediate the amnesia produced by isoflurane and do not mediate, or only partially mediate, the immobility produced by inhaled anesthetics.

Acoustic Stimulation↗
PubMed2005

Tutorial: context-sensitive decrement times for inhaled anesthetics.

Context-sensitive decrement times for inhaled anesthetics connect two values: a) the duration of anesthesia (nominally at a constant alveolar concentration)-the "context" and b) the time to decrease the alveolar or vital tissue (e.g., brain, heart, kidney, and liver, collectively called the vessel-rich group of tissues) concentration by some fractional "decrement" of the starting concentration. Increasing duration of anesthesia increases the time to a given decrement in a nonlinear manner that may considerably delay recovery. In the present report we use a commercially available simulation program (Gas Man) to confirm and enlarge on these concepts. In this simulation, increasing duration of anesthesia can markedly delay complete awakening for isoflurane. Increasing anesthesia duration imposes considerably less delay in awakening from sevoflurane compared with isoflurane. For desflurane, only prolonged anesthesia or decrements of 95% and more should delay awakening from anesthesia. These changes are shown to be the result of the relative solubility of each anesthetic in blood and tissue. An increase in cardiac output is also shown to delay awakening.

Anesthesia Recovery Period↗
PubMed2005

Temperatures in soda lime during degradation of desflurane, isoflurane, and sevoflurane by desiccated soda lime.

Rarely, fire and patient injury result from the degradation of sevoflurane by desiccated Baralyme. The present investigation sought to determine whether high temperatures also arose with sevoflurane use in the presence of desiccated soda lime. We desiccated soda lime by directing a 10 L/min flow of oxygen through fresh absorbent. Using 1140 +/- 30 g (mean +/- sd) of this desiccated absorbent, we filled a single standard absorber canister placed in a standard anesthetic circuit to which we directed a 6 L/min flow of oxygen containing 1.5 minimum alveolar concentration (MAC) desflurane or sevoflurane, or 3.0 MAC desflurane, isoflurane, or sevoflurane (with and without concurrent delivery of 200 mL/min carbon dioxide). In an additional test, 2 canisters (rather than a single canister) containing desiccated absorbent were used and 3.0 MAC sevoflurane was applied. A 3-L reservoir bag served as a surrogate lung, and we ventilated this lung with a minute ventilation of 10 L/min. With desflurane at 1.5 MAC or 3.0 MAC or isoflurane at 3.0 MAC temperatures increased in 20 to 40 min to a peak of 30 degrees C to 45 degrees C and then declined. With 1.5 or 3.0 MAC sevoflurane, temperatures increased to approximately 90 degrees C, after which temperatures declined. Concurrent delivery of carbon dioxide and sevoflurane did not increase the peak temperatures reached. The use of 2 canisters increased the duration but not the peak of increased temperature reached with 3.0 MAC sevoflurane. No fires resulted from degradation of any anesthetic.

Anesthetics, Inhalation↗
PubMed2004

Characteristics of anesthetic agents used for induction and maintenance of general anesthesia.

PURPOSE: The characteristics of ideal intravenous (i.v.) and inhaled anesthetic agents; the rationale for inducing anesthesia with i.v. anesthetics (particularly propofol); the rationale for inducing and maintaining anesthesia with inhaled anesthetics; and the advantages and disadvantages of specific inhaled anesthetics, namely, nitrous oxide, desflurane, halothane, isoflurane, and sevoflurane, are discussed. SUMMARY: Propofol has many characteristics of the ideal i.v. anesthetic, including a rapid, smooth induction of anesthesia and rapid clearance from the body. The use of an i.v. anesthetic such as propofol avoids the claustrophobia associated with the inhaled route. Inhaled anesthetics are preferred for maintenance of anesthesia because they allow a more precise control of the anesthetic state and do so at low cost. The ideal inhaled anesthetic agent has ample potency and a low solubility in blood and tissues (rapid recovery from anesthesia), resists physical and metabolic degradation, and protects and does not injure vital tissues. It also does not cause seizures, respiratory irritation, or circulatory stimulation or deplete the ozone layer. It has a low acquisition cost. Nitrous oxide potency is too small to produce anesthesia by itself. Halothane is too soluble and poses a risk of severe hepatotoxicity. Desflurane, isoflurane, and sevoflurane are preferred because they have an adequate potency, appropriate solubility, and minimal to no risk for hepatotoxicity. CONCLUSION: The utilization choice among desflurane, isoflurane, and sevoflurane is made by weighing specific advantages and disadvantages of each agent. The primary determining factors for use are anesthetic potency and control, rate of anesthesia induction, clearance from the body, and adverse effects.

Anesthesia, General↗
PubMed2004

Halothane depresses C-fiber-evoked windup of deep dorsal horn neurons in mice.

A progressive increase in the response of a nociceptive spinal neuron to repeated electrical C-fiber stimulation reflects a phenomenon called windup. Second order neurons in the dorsal horn, as well as motoneurons, can develop windup. Inhaled anesthetics act primarily in spinal cord to suppress movement induced by noxious stimulation. We hypothesized that halothane would depress neuronal windup in mice at concentrations that also prevented movement. We measured windup in deep dorsal horn neurons in lumbar spinal cord at 0.75 MAC (the minimum alveolar concentration of anesthetic that prevents movement in 50% of subjects in response to noxious stimulation), 0.9 MAC, and 1.1 MAC. The change from 0.75 to 0.9 MAC did not significantly decrease windup (-11+/-22%), but the change from 0.9 to 1.1 MAC decreased windup (-35+/-7%, P<0.01). We conclude that halothane depresses neuronal windup in the range that prevents movement, and that the effect on windup might play a role in halothane's immobilizing action.

Afferent Pathways↗
PubMed2004

Insulin decreases isoflurane minimum alveolar anesthetic concentration in rats independently of an effect on the spinal cord.

UNLABELLED: The observation that insulin supplies an element of analgesia suggests that insulin administration might decrease the concentration of inhaled anesthetic required to produce MAC (the minimum alveolar anesthetic concentration required to eliminate movement in response to noxious stimulation in 50% of subjects). We hypothesized that insulin decreases MAC by directly affecting the nervous system, by decreasing blood glucose, or both. To test these hypotheses, we infused increasing doses of insulin either intrathecally or IV in rats anesthetized with isoflurane and determined the resulting MAC change (assessing forelimb and hindlimb movement separately). Infusion of insulin produced a dose-related decrease in MAC that did not differ among groups. That is, the IV and intrathecal infusions caused similar decreases in MAC at a given infusion rate. Blood glucose concentrations were larger in the rats given insulin with 5% dextrose. However, the percentage change in MAC determined from forelimb versus hindlimb movement did not differ. For a given insulin infusion rate, MAC changes and glucose levels did not correlate with each other, except, possibly, for the most rapid infusion rate, for which smaller glucose concentrations were associated with a marginally larger decrease in MAC. Intrathecal infusions of insulin did not produce spinal cord injury. In summary, we found that insulin decreases isoflurane MAC in a dose-related manner independently of its effects on the blood concentration of glucose. The sites at which insulin acts to decrease MAC appear to be supraspinal rather than spinal. The effect may be due to a capacity of insulin to produce analgesia through an action on one or more neurotransmitter receptors. IMPLICATIONS: Intrathecal and IV insulin administration equally decrease isoflurane MAC in rats, regardless of the concentration of blood sugar. These findings indicate that although insulin decreases MAC, the decrease is not mediated by actions on the spinal cord.

Anesthetics, Inhalation↗
PubMed2004

Gamma-aminobutyric acidA receptors do not mediate the immobility produced by isoflurane.

Many inhaled anesthetics enhance the effect of the inhibitory neurotransmitter gamma aminobutyric acid (GABA), supporting the view that the GABAA receptor could mediate the capacity of inhaled anesthetics to produce immobility in the face of noxious stimulation (i.e., MAC, the minimum alveolar concentration required to suppress movement in response to a noxious stimulus in 50% of subjects). However, only limited in vivo data support the relevance of the GABAA receptor to MAC. In the present study we used two findings to test for the relevance of this receptor to immobilization for isoflurane: 1) differences among anesthetics in their capacity to enhance the response of receptor expression systems to GABA: isoflurane (considerable enhancement), xenon (minimal enhancement), and cyclopropane (minimal enhancement); and 2) studies showing that the spinal cord mediates MAC for isoflurane. If GABAA receptors mediate isoflurane MAC, then their blockade in the spinal cord should increase isoflurane MAC more than cyclopropane or xenon MAC and the MAC increase should be proportional to the in vitro enhancement of the GABAA receptor. To test this thesis, isoflurane, cyclopropane, or xenon MAC was determined in rats during intrathecal infusion of artificial cerebrospinal fluid (aCSF) via chronically implanted catheters. Then MAC was redetermined during infusion of 1 microL/min aCSF containing either 0.6 or 2.4 mg/mL picrotoxin, which noncompetitively blocks GABAA receptors. There was no consistent increase in MAC consequent to increasing the picrotoxin dose from 0.6 to 2.4 microg/min, which suggests that maximal blockade of GABAA receptors in the spinal cord had been achieved. Picrotoxin infusion increased MAC approximately 40% with all anesthetics. This indicates that GABA release in the spinal cord influences anesthetic requirement. However, the increase did not consistently differ among anesthetics and did not correlate with in vitro enhancement of GABAA receptors by these anesthetics. This supports the view that GABAA receptors do not mediate immobilization for isoflurane.

Anesthetics, Inhalation↗
PubMed2004

Inhibition of spinal protein kinase C-epsilon or -gamma isozymes does not affect halothane minimum alveolar anesthetic concentration in rats.

Anesthetic effects on receptor or ion channel phosphorylation by enzymes such as protein kinase C (PKC) have been postulated to underlie some aspects of anesthesia. In vitro studies show that anesthetic effects on several receptors are mediated by PKC. To test the importance of PKC for the immobility produced by inhaled anesthetics, we measured the effect of intrathecal injections of PKC-epsilon and -gamma inhibitors on halothane minimum alveolar anesthetic concentration (MAC) in 7-day-old and 21-day-old Sprague-Dawley rats. The inhibitors were made as solutions of 100 pmol/5 microL and were given in a volume of 5 microL (7-day-old [P7] rats) or 10 microL (21-day-old [P21] rats). Controls were saline injections or injections of the peptide carrier at the same concentration and volumes; there were six animals in each group. In P7 rats, MAC values (in percentage of an atmosphere) were 1.63 +/- 0.0727 (mean +/- SEM) in saline controls, 1.55 +/- 0.141 in carrier controls, 1.54 +/- 0.0800 in rats given PKC-epsilon, and 1.69 +/- 0.0554 in rats given PKC-gamma. In P21 animals, the values were 1.20 +/- 0.0490, 1.31 +/- 0.0124, 1.27 +/- 0.0367, and 1.15 +/- 0.0483, respectively. Injection of the inhibitors did not change MAC in either age group. These results do not support an anesthetic effect on phosphorylation as a mechanism underlying the capacity of inhaled anesthetics to prevent movement in response to noxious stimulation, and they indirectly support a direct action on receptors or ion channels.

Aging↗
PubMed2004

Isoflurane depresses windup of C fiber-evoked limb withdrawal with variable effects on nociceptive lumbar spinal neurons in rats.

Windup is a progressive increase in responses of nociceptive spinal cord neurons to repeated electrical C fiber stimulation. We hypothesized that isoflurane would depress windup at approximately the minimum alveolar anesthetic concentration (MAC) required to suppress purposeful movement in response to noxious stimulation. We recorded windup responses in single lumbar spinal neurons (n = 17) to a series of 15 repetitive electrical stimuli delivered at 1 Hz to the hindpaw at C fiber strength; hindpaw withdrawal force was simultaneously recorded. The total number of action potentials per 15 stimuli (mean +/- sem as a percentage of each neuron's maximal response) was 83% +/- 5%, 84% +/- 5%, 67% +/- 7%, and 57% +/- 8% at 0.7, 0.9, 1.1, and 1.4 MAC, respectively. The 0.9 and 1.1 MAC values differed significantly from each other, whereas the 0.7 and 0.9 MAC values differed from the 1.4 MAC value (P < 0.05). The reduced firing was attributed to a depression of the initial C fiber-evoked responses in most units, and a reduction in windup slope over the initial 5 stimuli in 6 units. Muscle force was 67%, 11%, and 4% of the 0.7 MAC value at 0.9, 1.1, and 1.4 MAC, respectively. Isoflurane depressed excitability and variably affected windup of lumbar spinal cord neurons, while uniformly depressing windup of limb withdrawals in a concentration-dependent manner.

Action Potentials↗
PubMed2004

Sevoflurane decreases bispectral index values more than does halothane at equal MAC multiples.

At the minimum alveolar concentration (MAC) of inhaled anesthetics, 50% of subjects move in response to noxious stimulation. Similarly, at MAC-awake, 50% of subjects respond appropriately to command. The bispectral index (BIS) nominally measures the effect of anesthetics on wakefulness or consciousness. We postulated that the use of halothane with a larger MAC-awake/MAC ratio than sevoflurane would produce higher BIS values at comparable levels of MAC. We studied 33 unpremedicated patients anesthetized by inhalation, 18 with sevoflurane and 15 with halothane. We measured BIS before and during anesthesia at 1 MAC, both before and after tracheal intubation facilitated by fentanyl and rocuronium and then at 1.5 MAC. BIS measurements were made after meeting steady-state conditions. No surgery was performed during this study. BIS values in awake patients did not differ between the sevoflurane and halothane groups (96 +/- 2 and 96 +/- 2, mean +/- sd, respectively). At 1 MAC without and with neuromuscular blockade and at 1.5 MAC, BIS values for patients anesthetized with halothane (54 +/- 7, 56 +/- 7, and 49 +/- 7, respectively) exceeded those for patients anesthetized with sevoflurane (34 +/- 6, 34 +/- 6, and 29 +/- 5, respectively) (P < 0.0001). This finding adds to other evidence indicating that BIS is drug specific.

Adult↗
PubMed2004

Fires from the interaction of anesthetics with desiccated absorbent.

Rarely, fire and patient injury have resulted from the degradation of sevoflurane by desiccated carbon dioxide absorbent. Desiccated absorbent also can degrade desflurane and isoflurane, and in the present investigation we sought to determine whether a danger of fire also arose with their use in the presence of desiccated absorbent. Baralyme was desiccated by heating and directing a 10 L/min flow of oxygen through the absorbent. Approximately 1200 g of this desiccated absorbent was used to fill a standard absorber placed in a standard anesthetic circuit to which we directed a 6 L/min flow of oxygen containing 1.5 or 3.0 MAC desflurane, isoflurane, or sevoflurane. A 3-L reservoir bag served as a surrogate lung, and we ventilated this lung with a minute ventilation of 10 L/min. With desflurane or isoflurane, at both 1.5 MAC and 3.0 MAC, temperatures increased in 30 to 70 min to a peak of approximately 100 degrees C and then decreased. With 1.5 MAC sevoflurane (3.0 MAC was not studied), temperatures increased to over 200 degrees C, and in 2 of 5 studies, flames appeared in the anesthetic circuit. In a separate study, we found that concurrent delivery of carbon dioxide and desflurane did not increase peak temperatures. We conclude that the interaction of desflurane or isoflurane with desiccated absorbent is not likely to produce the conflagrations possible with sevoflurane.

Barium Compounds↗