Halothane Anesthesia Research Articles

Urinary lipid and protein oxidation products upon halothane, isoflurane, or sevoflurane anesthesia in humans: potential biomarkers for a subclinical nephrotoxicity

Objective: To investigate whether lipid and protein oxidation products are elevated and correlated with routine clinical markers of hepatic and renal function in patients anesthetized with halothane, isoflurane, or sevoflurane.Methods: Urine and blood samples were collected from patient groups. Excretion of aldehydes, acetone, and o,o’-dityrosine was measured before and after anesthesia. Blood samples were analysed for clinical markers.Results: Urinary concentrations of aldehydes, acetone, o,o’-dityrosine and glucose were significantly increased after anesthesia in halothane and sevoflurane groups earlier than clinical markers. Significant correlations were found in sevoflurane group.Conclusion: Lipid and protein oxidation contributes to subclinical sevoflurane nephrotoxicity. Oxidation products may serve as early biomarkers.

Noxious stimulation excites serotonergic neurons: A comparison between the lateral paragigantocellular reticular and the raphe magnus nuclei

The present study was designed to record electrophysiological responses to graded noxious thermal stimuli of serotonergic and nonserotonergic neurons in the lateral paragigantocellular reticular (LPGi) and the raphe magnus (RMg) nuclei in rats. All of the neurons recorded were juxtacellularly filled with neurobiotin and identified with double immunofluorescent labeling for both neurobiotin and serotonin. Under halothane anesthesia (0.75%), noxious thermal stimuli ⩾48°C activated almost all (88%) of the serotonergic neurons located within the LPGi (n=16). The increase in firing was clear (3.4±0.3spike/s: mean of responses above the population median) and sustained during the whole application of strong thermal noxious stimuli, with a high mean threshold (48.3±0.3°C) and large receptive fields. Recording of serotonergic neurons in the RMg (n=21) demonstrated that the proportion of strongly activated (>2spike/s) neurons (19% vs 59% for the LPGi) as well as the magnitude of the activation (2.1±0.4spike/s: mean of responses above the population median) to thermal noxious stimuli were significantly lower than in the LPGi (P<.05). Within the boundaries of both the LPGi and the RMg (B3 group), nonserotonergic neurons were also predominantly excited (75%) by noxious stimuli, and the resulting activation (7.9±1.2spike/s) was even greater than that of serotonergic neurons. Thermal noxious stimuli–induced activation of LPGi serotonergic cells probably plays a key role in serotonin-mediated modulations of cardiac baroreflex and transmission of nociceptive messages occurring under such intense noxious conditions.

The effect of aging on dopamine release and metabolism during sevoflurane anesthesia in rat striatum: An in vivo microdialysis study

We have previously reported that halothane anesthesia increases extracellular concentrations of dopamine (DA) metabolites in rat striatum using in vivo microdialysis techniques. Aging induces many changes in the brain, including neurotransmission. However, the relationship between aging and changes in neurotransmitter release during inhalational anesthesia has not been fully investigated. The aim of the present investigation was to evaluate the effect of sevoflurane on methamphetamine (MAPT)-induced DA release and metabolism in young and middle-aged rats. Male Sprague-Dawley rats were implanted with a microdialysis probe into the right striatum. The probe was perfused with a modified Ringer's solution and 40μl of dialysate was directly injected to an HPLC every 20min. Rats were administered saline, the same volume of 2mgkg(-1) MAPT intraperitoneally, or 5μM MAPT locally perfused. After treatments, the rats were anesthetized with 1% or 3% sevoflurane for 1h. Sevoflurane anesthesia significantly increased the extracellular concentration of DA only in middle-aged rats (52-weeks-old). In young rats (8-weeks-old), sevoflurane significantly enhanced MAPT-induced DA when administered both intraperitoneally and perfused locally, whereas no significant additive interaction was found in middle-aged rats. These results suggest that aging changes DA release and metabolism in rat brains primarily by decreasing the DA transporter.

Effects of halothane on GABAergic and glutamatergic transmission in isolated hippocampal nerve-synapse preparations

We evaluated the effects of halothane on synaptic and extrasynaptic GABAA and glutamate receptor responses using mechanically dissociated rat hippocampal CA3 neurons in which the well isolated neurons retain functional native nerve endings (the ‘synaptic bouton’ preparation). The preparation allows the simultaneous comparison of extrasynaptic GABAA and glutamate receptors, activated by bath applied GABA and glutamate, respectively, to the synaptic receptors measured as spontaneous and evoked postsynaptic currents. Paired-pulse synaptic responses evoked by focal electrical stimulation were also measured to evaluate any presynaptic effects. Halothane enhanced the extrasynaptic GABAA-receptor mediated postsynaptic responses in a concentration dependent fashion. At clinically relevant concentrations, halothane significantly increased both the amplitude and frequency of spontaneous postsynaptic inhibitory currents (sIPSCs) mediated by synaptic GABAA receptors. The relative amplitude of evoked IPSCs (eIPSCs) was also increased, concurrent with a decrease in failure rate and a significantly decreased eIPSC paired-pulse ratio. Halothane concentration dependently decreased the extrasynaptic glutamate-receptor induced postsynaptic responses but had no effects on spontaneous or evoked excitatory postsynaptic currents. These results suggest that halothane acts predominantly at presynaptic sites at GABAergic synapses to enhance inhibitory transmission at CA3 synapses, although it also increases extra-synaptic GABA responses. At excitatory synapses on to CA3 neurons, halothane has no presynaptic action—effecting only extrasynaptic receptors. Our results have clarified the locus of effects of the volatile anesthetic halothane at excitatory and inhibitory synapses, drawing somewhat different conclusions from those deduced from slices and culture systems.

Design and biophysical characterization of a monomeric four-alpha-helix bundle protein Aα4 with affinity for the volatile anesthetic halothane

A monomeric four-α-helix bundle protein Aα4 was designed as a step towards investigating the interaction of volatile general anesthetics with their putative membrane protein targets. The alpha helices, connected by glycine loops, have the sequence A, B, B′, A′. The DNA sequence was designed to make the helices with the same amino acid sequences (helix A and A′, B and B′, respectively) as different as possible, while using codons which are favorable for expression in E. coli. The protein was bacterially expressed and purified to homogeneity using reversed-phase HPLC. Protein identity was verified using MALDI–TOF mass spectrometry. Far-UV circular dichroism spectroscopy confirmed the predominantly alpha-helical nature of the protein Aα4. Guanidinium chloride induced denaturation showed that the monomeric four-α-helix bundle protein Aα4 is considerably more stable compared to the dimeric di-α-helical protein (Aα2-L38M)2. The sigmoidal character of the unfolding reaction is conserved while the sharpness of the transition is increased 1.8-fold. The monomeric four-α-helix bundle protein Aα4 bound halothane with a dissociation constant (Kd) of 0.93±0.02mM, as shown by both tryptophan fluorescence quenching and isothermal titration calorimetry. This monomeric four-α-helix bundle protein can now be used as a scaffold to incorporate natural central nervous system membrane protein sequences in order to examine general anesthetic interactions with putative targets in detail.

Surgical Correction of Uterine Torsion and Mare–Foal Survival in Advance Pregnant Equine Patients

This article describes the surgical management of uterine torsion by midline celiotomy and cesarean section on 12 mares presented with signs of colic to a teaching veterinary hospital. The mares were either in full term of gestation (n = 7) or in advanced stage of pregnancy (n = 5). Six mares were in first parity. Uterine torsion was diagnosed by per rectal and per vaginal examinations. For surgical intervention, mares were anesthetized using a combination of xylazine (1.1 mg/kg) and ketamine (2.2 mg/kg), intravenously. After intubation, the animals were maintained on halothane (n = 4) or isoflurane (n = 8) inhalation anesthesia. Midline celiotomy was performed, and foals were delivered by cesarean section. In 11 mares, before closing the abdominal wound, the uterus was detorted manually and confirmed for its normal position. Both anesthetic protocols using halothane and isoflurane were found satisfactory for surgical correction of uterine torsion. After long-term follow-up, the study reported 75.0% (9/12) survival rate for mares. One mare was euthanized because of devitalized, necrosed, and adhered uterus to the abdominal wall. Of the nine surviving mares, seven were successfully bred. Three foals were born alive, and only one could survive on long-term basis. Of the nine dead foals, two had umbilical cord torsion.

Trifluoroacetate is an allosteric modulator with selective actions at the glycine receptor

Trifluoroacetic acid is a metabolite of the inhaled anesthetics halothane, desflurane and isoflurane as well as a major contaminant in HPLC-purified peptides. Ligand-gated ion channels, including cys-loop receptors such as the glycine receptor, have been the targets of peptide-based drug design and are considered to be likely candidates for mediating the effects of anesthetics in vivo, but the possible secondary contributions of contaminants and metabolites to these effects have not been studied. We used two-electrode voltage-clamp electrophysiology to test glycine, GABAA and 5-HT3 receptors expressed in Xenopus oocytes for their sensitivities to sodium trifluoroacetate.Trifluoroacetate (100μM–3mM) enhanced the currents elicited by low concentrations of glycine applied to α1 homomeric and α1β heteromeric glycine receptors, but it had no effects when co-applied with a maximally-effective glycine concentration. Trifluoroacetate had no effects on α1β2γ2S GABAA or 5-HT3A receptors at any GABA or serotonin concentration tested.The results demonstrate that trifluoroacetate acts as an allosteric modulator at the glycine receptor with greater specificity than other known modulators. These results have important implications for both the secondary effects of volatile anesthetics and the presence of contaminating trifluoroacetate in HPLC-purified peptides, which is potentially an important source of experimental variability or error that requires control.

Gabapentin Augments the Antihyperalgesic Effects of Diclofenac Sodium Through Spinal Action in a Rat Postoperative Pain Model

Gabapentin and nonsteroidal antiinflammatory drugs (NSAIDs) attenuate postoperative pain and neuropathic pain in humans. The combination of gabapentin and NSAIDs is effective for postoperative pain and enhances functional recovery after surgery. Intrathecal administration of gabapentin or NSAIDs inhibits hyperalgesia in a rat postoperative pain model. However, there is no information on the effects of intrathecal administration of a combination of gabapentin and NSAIDs. We therefore investigated the effects of intrathecal administration of gabapentin and NSAIDs in a rat model of postoperative pain. Rats were prepared for intrathecal catheters under halothane anesthesia. Two days after catheterization, gabapentin (4, 40, or 400 μg per 20 μL of saline), diclofenac sodium, a nonselective cyclooxygenase inhibitor (2, 20, or 200 μg per 20 μL of 6% glucose), 20 μL saline, 20 μL 6% glucose, and a combination of gabapentin and diclofenac (40 μg gabapentin + 20 μg diclofenac and 4 μg gabapentin + 2 μg diclofenac per 20 μL 6% glucose) were injected intrathecally. We performed a hindpaw incision 30 minutes after injection. Each group consisted of 6 rats. The mechanical threshold was measured to evaluate secondary hyperalgesia using von Frey filaments before intrathecal catheterization and at 2 hours, and 1, 3, 5, and 7 days after paw incision. Gabapentin 400 μg attenuated mechanical hyperalgesia for 7 days compared with the control group. Diclofenac 200 μg inhibited hyperalgesia for 5 days compared with the control group. The 40 μg gabapentin + 20 μg diclofenac group had a significantly reduced secondary hyperalgesic response in 2 hours and 1 day compared with 40 μg gabapentin and 20 μg diclofenac, respectively. The 4 μg gabapentin + 2 μg diclofenac group had a significantly reduced secondary hyperalgesic response in 2 hours and 1 day compared with 2 μg diclofenac. The withdrawal threshold on the contralateral paw did not change compared with the preincision threshold. Intrathecal administration of gabapentin and diclofenac in combination reduced secondary hyperalgesia at doses having no antihyperalgesic effects when given individually. Our results suggest that gabapentin and diclofenac have an important role in postoperative pain reduction at the spinal level, and that gabapentin augments the antihyperalgesic effects of diclofenac through action in the spinal cord.

Differential Effects of Anaesthesia on the phMRI Response to Acute Ketamine Challenge

AIMS: Pharmacological-challenge magnetic resonance imaging (phMRI) is powerful new tool enabling researchers to map the central effects of neuroactive drugs in vivo. To employ this technique pre-clinically, head movements and the stress of restraint are usually reduced by maintaining animals under general anaesthesia. However, interactions between the drug of interest and the anaesthetic employed may potentially confound data interpretation. NMDA receptor (NMDAR) antagonists used widely to mimic schizophrenia have recently been shown to interact with the anaesthetic halothane. It may be the case that neural and cerebrovascular responses to NMDAR antagonists are dependent on the types of anaesthetic used. METHODOLOGY: We compared the phMRI response to NMDAR antagonist ketamine in rats maintained under α-chloralose to those under isoflurane anaesthesia. A randomized placebo/vehicle controlled design was used in each of the anaesthetic groups. RESULTS: Changes in the anaesthetic agent resulted in two very different profiles of activity. In the case of α-chloralose, positive activations in cortical and sub-cortical structures reflected a response which was similar to patterns seen in healthy human volunteers and metabolic maps of conscious rats. However, the use of isoflurane completely reversed such effects, causing widespread deactivations in the cortex and hippocampus. CONCLUSION: This study provides initial evidence for a drug-anesthetic interaction between ketamine and isoflurane that is very different from responses to α-chloralose-ketamine.

Extraction of best set of parameters derived from electroencephalogram for the prediction of awake and sleeps state of the patient

The study describes a best set of parameters of electroencephalogram (EEG) for prediction of awake and anaesthetic sleep state of the patient during halothane anaesthesia. After obtaining the proper approval of hospital ethics committee and written consent from the patients, EEG data of 60 patients were recorded in normal awake and anesthetised sleep state. The recorded EEG data of all patients in each state was partitioned into different epochs of four-second duration. Algorithms were written to compute the 21 identified parameters of EEG, which are known to vary with variation in anaesthetic drug. Principal component analysis (PCA) is applied on these 21 parameters of EEG to find out the best parameters. Three parameters were identified which distinguish the awake and anesthetised sleep state of the patient. By using these identified parameters, whole data is divided into two different groups, i.e., training data and testing data. Artificial neural network (ANN) was trained with training data and target matrix. On testing with unknown epochs of testing data, this artificial neural network (ANN) has given 100% accuracy for the prediction of the state of the patient.

Anesthetic Concentrations of Halothane Change the Domain Structure of Mixed Lipid Membranes

Binary and ternary mixtures of lipids that form separate phases (gel, fluid-ordered, and fluid disordered) may provide useful insights into the complex physics of real biological membranes. Here, we examine the mixing versus temperature of DPPC:DLPC and DPPC:DOPC:Cholesterol phase separated systems using neutron and x-ray diffraction methods. We also report the affects of inhalation anesthetics on the phase behavior of these lipid mixtures. Phase co-existence was measured by lamellar x-ray diffraction from multi-layer samples. Two distinct series of lamellar Bragg diffraction were observed demonstrating separation into distinct 3D phases. We observe a broad transition in which one phase diminishes as a function of temperature resulting in a single homogenous phase. We used isotopic contrast from chain deuterated lipids to show compositional changes in the fluid phase during the mixing transition. The changes seen in the proportion of lipids in the lamellar diffraction studies correspond to physical mixing of the lipid species shown by examining the chain diffraction at wide angles produced by deuterated lipids. Finally, we show that the anesthetic halothane shifts the temperature mixing curves and sharpens the transition of these mixtures.

Sevoflurane: A Potent General Anesthetic Enhancer of Kv Channel Activation

General anesthetics have been shown to both inhibit and potentiate various families of ion channels. However, the molecular bases of these actions are not understood. Previous work with K-Shaw2 explored structural determinants of inhibition by alkanols and the volatile general anesthetics halothane and isoflurane (Barber et al. Biophys J. 2011, in press). In this study, we report that sevoflurane, an inhaled anesthetic currently used in human general anesthesia, exhibits the singular ability to reversibly potentiate K-Shaw2 currents investigated in Xenopus oocytes under two-electrode voltage-clamp conditions (∼80% potentiation at 1 mM). This result is in sharp contrast to the action of multiple other inhaled (halothane, isoflurane, desflurane, chloroform, and 1-alkanols) and injected (propofol) general anesthetics, which are inhibitory. This potentiation occurs over a clinically relevant concentration range (0.05 - 1 mM) in a dose-dependent manner that suggests two binding sites with distinct apparent affinities: a high-affinity site (K1 = 60 μM) and a low affinity site (K2 = 4 mM). Furthermore, a double mutation involving the S6 segment and the S4-S5 linker (A326V/A417V) abolishes the potentiation by sevoflurane. This effect is especially interesting because this double mutation also abolishes the inhibitory action of halothane, suggesting that these inhaled anesthetics share effector sites but influence gating in opposite ways. Semiquantitative kinetic modeling suggests that preferential binding of sevoflurane to resting and activated closed states shifts the channels into a novel gating mode with an enhanced open probability. Additional screening of related voltage-gated K channels at a various doses of sevoflurane revealed only modest potentiation of Kv1.2 no effect on Kv1.3, Kv2.1, Kv3.4 and Kv4.2. This study provides a novel framework for further investigations of the structural basis of general anesthetic action.

Anesthetic Mechanisms: Worms Light the Way

In the nematode C.elegans, immobility induced by the anesthetic halothane is coupled to its ability to modulate neuronal resting membrane potential, perhaps through effects on leak channels; a similar anesthetic, isoflurane, appears to work a different way.

Mice expressing T4826I‐RYR1 are viable but exhibit sex‐ and genotype‐dependent susceptibility to malignant hyperthermia and muscle damage

Mutation T4825I in the type 1 ryanodine receptor (RYR1(T4825I/+)) confers human malignant hyperthermia susceptibility (MHS). We report a knock-in mouse line that expresses the isogenetic mutation T4826I. Heterozygous RYR1(T4826I/+) (Het) or homozygous RYR1(T4826I/T4826I) (Hom) mice are fully viable under typical rearing conditions but exhibit genotype- and sex-dependent susceptibility to environmental conditions that trigger MH. Hom mice maintain higher core temperatures than WT in the home cage, have chronically elevated myoplasmic[Ca(2+)](rest), and present muscle damage in soleus with a strong sex bias. Mice subjected to heat stress in an enclosed 37°C chamber fail to trigger MH regardless of genotype, whereas heat stress at 41°C invariably triggers fulminant MH in Hom, but not Het, mice within 20 min. WT and Het female mice fail to maintain euthermic body temperature when placed atop a bed whose surface is 37°C during halothane anesthesia (1.75%) and have no hyperthermic response, whereas 100% Hom mice of either sex and 17% of the Het males develop fulminant MH. WT mice placed on a 41°C bed maintain body temperature while being administered halothane, and 40% of the Het females and 100% of the Het males develop fulminant MH within 40 min. Myopathic alterations in soleus were apparent by 12 mo, including abnormally distributed and enlarged mitochondria, deeply infolded sarcolemma, and frequent Z-line streaming regions, which were more severe in males. These data demonstrate that an MHS mutation within the S4-S5 cytoplasmic linker of RYR1 confers genotype- and sex-dependent susceptibility to pharmacological and environmental stressors that trigger fulminant MH and promote myopathy.

Therapeutic effects of postischemic treatment with hypotensive doses of an angiotensin II receptor blocker on transient focal cerebral ischemia

Neurovascular protection against cerebral ischemia is not consistently observed with a postischemia hypotensive dose of candesartan. The aim of this study was to determine the levels of brain angiotensin II after reperfusion and the efficacy and therapeutic time window of postischemic treatments with hypotensive doses of candesartan for the treatment of cerebral ischemia. Occlusions of the right middle cerebral artery (60 min) followed by reperfusion were performed using the thread method under halothane anesthesia in Sprague-Dawley (SD) rats. Protein levels of brain angiotensin II and mRNA levels of renin-angiotensin system components were evaluated following reperfusion (n=184 in total). Low-dose or high-dose treatments with candesartan cilexetil (1 or 10 mg/kg per day, respectively) were administered orally immediately following reperfusion once daily for 4 or 7 days (n = 119 in total). An additional group was treated with low-dose candesartan cilexetil after a 12-h delay based on the brain angiotensin II levels (n = 14). Levels of brain angiotensin II transiently increased 4-12 h after reperfusion, which followed an increase in angiotensinogen mRNA. Candesartan cilexetil treatments significantly reduced blood pressure (BP) in rats administered the high dose and moderately in rats receiving the low dose. A low dose of candesartan cilexetil reduced the infarct size, cerebral edema, and neurological deficits, whereas the high-dose treatments showed limited reductions. Furthermore, oxidative stress following reperfusion was reduced with the low-dose treatments. The therapeutic time window was open for at least 12 h after reperfusion when brain angiotensin II levels had peaked. Postischemic treatments using low hypotensive doses of candesartan cilexetil provided protection against cerebral ischemic injury and may have a clinically relevant therapeutic time window.

Different genes influence toluene- and ethanol-induced locomotor impairment in C. elegans

BackgroundThe abused volatile solvent toluene shares many behavioral effects with classic central nervous system depressants such as ethanol. Similarities between toluene and ethanol have also been demonstrated using in vitro electrophysiology. Together, these studies suggest that toluene and ethanol may be acting, at least in part, via common mechanisms. MethodsWe used the genetic model, Caenorhabditis elegans, to examine the behavioral effects of toluene in a simple system, and used mutant strains known to have altered responses to other CNS depressants to examine the involvement of those genes in the motor effects induced by toluene. ResultsToluene vapor brings about an altered pattern of locomotion in wild-type worms that is visibly distinct from that generated by ethanol. Mutants of the slo-1, rab-3 and unc-64 genes that are resistant to ethanol or the volatile anesthetic halothane show no resistance to toluene. A mutation in the unc-79 gene results in hypersensitivity to ethanol, halothane and toluene indicating a possible convergence of mechanisms of the three compounds. We screened for, and isolated, two mutations that generate resistance to the locomotor depressing effects of toluene and do not alter sensitivity to ethanol. ConclusionsIn C. elegans, ethanol and toluene have distinct behavioral effects and minimal overlap in terms of the genes responsible for these effects. These findings demonstrate that the C. elegans model system provides a unique and sensitive means of delineating both the commonalities as well as the differences in the neurochemical effects of classical CNS depressants and abused volatile inhalants.

Postoperative agitation in preschool children following emergence from sevoflurane or halothane anesthesia: A randomized study on the forestalling effect of midazolam premedication versus parental presence at induction of anesthesia

Objective The effect of midazolam premedication on forestalling postoperative agitation in children is not yet concluded. The purpose of this study was to compare the effects of midazolam premedication and parental presence during anesthetic induction on the incidence of postoperative agitation in pediatric patients. Methods One hundred sixty-seven children between 2 years and 7 years of age, undergoing anesthesia for outpatient surgery, were enrolled and randomly divided into four groups: sevoflurane anesthesia with parental presence without premedication, sevoflurane anesthesia with oral midazolam premedication, halothane anesthesia with parental presence without premeditation, and halothane anesthesia with oral midazolam premedication. The children randomized to the premedication groups took oral midazolam 0.5 mg/kg 20–30 minutes before anesthetic induction. For patients in the groups without premedication, one of the parents was present throughout the induction of anesthesia. One recovery room nurse blinded to the group assignment observed the patients and recorded the agitation scores all through their stay in the postanesthesia care unit. Results Postoperative agitation was significantly less in patients who received halothane anesthesia with oral midazolam premedication ( p < 0.002). Conclusion Based on our data, the presence of a parent at induction of sevoflurance anesthesia was as effective as midazolam premedication in decreasing the incidence of postoperative agitation. Midazolam premedication, however, decreased postoperative agitation when halothane was used as the anesthetic agent.

Intrinsic interaction mode of an inhalation anesthetic with globular proteins: a comparative study on ligand recognition

Interaction mode of an inhalation anesthetic halothane with water-soluble globular proteins, myoglobin (Mgb) and lysozyme (Lys), was studied by differential scanning calorimetry (DSC) and viscometry, and the results were compared with those of bovine serum albumin (BSA). The anesthetic sensitivity was markedly different among the proteins: Mgb was destabilized, Lys was slightly destabilized, and BSA was conversely stabilized. Further, the interaction mode was quite different from those of specific binders for the proteins. The anesthetic sensitivity was highly correlated with the hydrophilicity on the protein surface (Mgb < Lys < BSA) and the rigidity of the protein structure (BSA ≈ Mgb < Lys). We showed that the anesthetic sensitivity among globular proteins can be roughly classified into four categories, and proteins with small hydrophilicity and soft structure are suitable as model proteins of anesthesia. By contrast, the binding of the specific binders was characterized by the lower effective concentrations. The molar ratio of the binder to the protein at the effective concentration was well consistent with the binding number determined from the X-ray structural analysis. Moreover, the interaction mode of the binder was not necessarily in accord with the mode expected from the change in the protein structure. Considering the above facts, we can systematically interpret the effect of an anesthetic on globular proteins by four factors: (1) hydrophobicity of an anesthetic, (2) hydrophilicity of a protein surface, (3) rigidity of a protein structure, and (4) molar ratio of an anesthetic to a protein at the effective concentration.

ChemInform Abstract: Halogen Bonding in Halocarbon—Protein Complexes: A Structural Survey

AbstractReview: 42 refs.

Changes in EEG and Bispectral Index in Children during Inhalation Anesthesia

Objective: to estimate bispectral (BIS) index and electroencephalographic (EEG) changes during anesthesia with halothane, sevoflurane, and a successive combination of sevoflurane and isoflurane, by taking into account age. Subjects and methods. Sixty children aged 3 to 17 years, who had undergone elective surgery, were randomized to 3 groups of 20 children each: 1) halothane anesthesia; 2) sevoflurane anesthesia; and 3) a successive combination of sevoflurane and isoflurane. A 1:1 oxygen-nitrous oxide mixture was used for anesthesia in all the groups. EEG (using a 6-channel computer-assisted encephalograph) and bispectral index (XP version) was continuously recorded throughout the anesthesia, except the transition to isoflurane in Group 3. Results. In the halothane group, EEG displayed a gradual reduction in basic rhythm, an increase in slow activity with the rhythm being recovered on emergence. The BIS index changed from 96—99 to 19—36 with a spike of up to 80—87 on emergence. In Groups 2 and 3 where the induction of anesthesia used sevoflurane, EEG recorded a pointed а-rhythm, increased amplitude, and rhythm synchronization. The BIS value changed from 96—99 to 19—37. In Group 2, it was 30 to 40 on anesthesia maintenance and up to 82—87 on emergence. In Group 3, the isofluorane anesthesia stage changed EEC patterns towards rhythm synchronization and gave rise to slow fluctuations in all leads. The BIS index was 30—39 on anesthesia maintenance and 80—86 on emergence. Conclusion. EEC and BIS index monitoring values corresponded to the clinical course and depth of anesthesia. The comparison of the clinical data of the course of anesthesia and the values of EEG and BIS monitoring could lead to the conclusion that BIS technology might be of informative value in children. Key words: inhalation anesthesia, electroencephalography, BIS monitoring, isoflurane, sevoflurane, halothane.