Changes in blood chemistries following prolonged enflurane anesthesia

In an effort to identify further the structural requirements for central dopamine receptor agonists, some monohydroxyl analogs of the known agonist 5,6-dihydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene were synthesized. They were examined for production of emesis in dogs and stereotyped behavior in rats. The most potent was 5-hydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene, which was more potent than apomorphine but less so than the dihydroxyl analog. The two enantiomers of the monohydroxyl analog were synthesized by conventional methods from an optically active intermediate, 2-benzylamino-5-methoxy-1,2,3,4-tetrahydronaphthalene. The resolution of this amine was performed with the aid of mandelic acid. Dopaminergic activity was found to be confined to the levo enantiomer. Requirements for both substitution and chirality in the tetralines were found to correspond closely to those known for the dopaminergic aporphines.     

Fuzzy-logic control of blood pressure through enflurane anesthesia

BACKGROUND: A 190k (190-kilodalton) membrane protein has been identified in several multidrug-resistant (MDR) cell lines that show decreased drug accumulation without expression of P-glycoprotein. It is not clear whether this 190k protein is involved directly in drug efflux. Recently, a gene for a putative transporter protein, MRP (multidrug resistance-associated protein) has been sequenced and localized to chromosome 16. The protein encoded by this gene contains a 7-amino-acid sequence present in the synthetic peptide used to generate the antiserum recognizing the 190k protein. PURPOSE: The study was undertaken to clarify the relationship of the 190k protein to MRP gene expression in non-P-glycoprotein-containing MDR cells of the large-cell and adenocarcinoma lung cancer lines, COR-L23 and MOR. METHODS: Expression of the 190k protein was determined by Western blot analysis and that of the MRP gene by polymerase chain reaction amplification of complementary DNA reverse transcribed from RNA. Abnormalities of chromosome 16 were investigated in chromosome spreads by fluorescence in situ hybridization. RESULTS: The amount of detectable 190k protein is closely associated with degree of drug resistance. Cell lines surviving in higher drug concentrations have greater amounts of protein, and revertant lines grown without drug for up to 28 weeks show reduced expression of the protein together with enhanced drug sensitivity. The 190k protein appears to be one of the major proteins differentially expressed in membranes of drug-resistant cells. The amount of MRP messenger RNA correlates closely with that of the 190k protein. The MDR cells contain amplified chromosome 16 material with many double minutes in the large-cell lung tumor lines and an enlarged chromosome 16 in the adenocarcinoma lines. CONCLUSION: The 190k protein detected immunologically is likely to be the protein, encoded by the MRP gene, which becomes overexpressed in these cells as a consequence of chromosomal amplification and fragmentation. IMPLICATION: Though associated with drug resistance, enhanced drug efflux, and decreased drug accumulation in cell lines, the role of this protein in clinical resistance has yet to be determined.     

Inorganic fluoride nephrotoxicity: prolonged enflurane and halothane anesthesia in volunteers

The effects of prolonged enflurane and halothane administration on urine-concentrating ability were determined in volunteers by examining their responses to vasopressin before anesthesia and on days 1 and 5 after anesthesia. A significant decrease in maximum urinary osmolality of 264 +/- 34 mOsm/kg (26 per cent of the preanesthetic value) was present on day 1 after enflurane anesthesia, whereas subjects anesthetized with halothane had a significant increase in maximum urinary osmolality of 120 +/- 44 mOsm/kg. Serum inorganic fluoride level peaked at 33.6 muM and remained above 20 muM for approximately 18 hours. Thus, the threshold level for inorganic fluoride nephrotoxicity is lower than previously suspected.     

Failure of enflurane and halothane anesthesia to inhibit lymphocyte transformation in volunteers

Changes in the peripheral blood leukocyte count and in the ability of lymphocytes to transform in response to phytohemagglutinin were studied in healthy volunteers undergoing prolonged enflurane or halothane anesthesia without coincident surgical operation. Anesthesia was associated with a modest leukocytosis that persisted into the first post-anesthesic day, primarily due to an influx of neutrophils into the circulation. There was no significant alteration, either during or following anesthesia, in the ability of the volunteers' lymphocytes to transform in response to phytohemagglutinin when compared with either preanesthetic values or unanesthetized controls. Depression of lymphocyte transformation does not appear to follow prolonged enflurane or halothane anesthesia in the absence of a surgical procedure.     

EEG-changes during general anaesthesia with enflurane (Efrane) in comparison with ether

The effects of enflurane (efrane) and ether on the cerebral functions were studied by EEG on two similar groups of adult patients. For basic comparison a depth of anaesthesia was chosen which permitted abdominal surgery without the need to administer muscular relaxants. At this level of anaesthesia the typical EEG-changes of paroxysmal type which have been described with enflurane were seen only occasionally. If, however, the depth of anaesthesia was further increased, such EEG-changes indicating increased cerebral excitability were seen more often under enflurane and also appeared under ether anaesthesia. No seizure activity was recorded.     

Effect of remifentanil on clinical and electroencephalographic parameters of depth of anesthesia in balanced anesthesia with propofol, enflurane or isoflurane

Electrophysiological parameters are well-suited to detect changes in cerebral function. The present study investigates whether balanced anaesthesia with remifentanil during nociceptive stimulation is associated with changes in clinical and electrophysiological parameters indicating inadequate depth of anaesthesia. Following IRB approval and written informed consent, 23 patients (ASA: I; age: 36 +/- 11) scheduled for elective gynaecological laparoscopy were included in the study. Without any premedication, anaesthesia was induced with remifentanil (1.0 microgram/kg bolus injection), propofol (0.5 mg/kg added by repetitive (10 mg) bolus injections every 10 s until unconciousness) and vecuronium (0.1 mg/kg). Following endotracheal intubation (normoventilation: PetCO2: 36 bis 38 mmHg), remifentanil infusion was started with continuous doses of 0.5 microgram/kg/min over 5 minutes and maintained with 0.25 microgram/kg/min during surgery. Remifentanil was randomly combined with propofol (group 1: 100 micrograms/kg/min; n = 7), enflurane (group 2: 0.5 MAC; n = 8) or isoflurane (group 3: 0.5 MAC; n = 8). Monitoring included: heart rate (beats/min), mean arterial pressure (mmHg), oxygen saturation (%), endtidal CO2 (mmHg) and endtidal enflurane and isoflurane (%). EEG: 2-channel recordings of Fz versus mastoid and ECG (artefact control) during steady-state anaesthesia and surgery. Following fast-fourier-transformation (4 s; 256/s; 0.5 to 35.0 Hz), spectral power densities were calculated for the selected frequency bands. Auditory evoked potentials (AEP; middle latency) were registered simultaneously after binaural stimulation via head-phones click-stimulation (6 Hz; 75 dB above hearing threshold; 512 stimulations per average). Bandpass was 0.01 to 2.0 kHz. Analysis: Na, Pa, Nb (latencies; ms) and peak-to-peak amplitudes (NaPa, PaNb; microV). EEG and AEP recording technique [15]. The study protocol included baseline values from pre-intubation, pre-surgery, the respective post-stimulation values (1 min, 3 min, 5 min) and all data at five-minute intervals during surgery until emergence from anaesthesia. During steady-state study conditions with defined remifentanil applications, mean data indicate that in response to nociceptive stimuli no changes in clinical or electrophysiological parameters were observed. In contrast to other studies using different anaesthetic techniques, the present data from remifentanil indicate very stable haemodynamic and electrophysiological parameters (EEG, AEP) during noxious stimulations. Adjustable and with no plasma accumulation, remifentanil demonstrates potent antinociceptive effects resulting in signs of adequate anaesthesia.     

Carotid endarterectomy under regional (conductive) anesthesia

Carotid endarterectomy is reliable in the prevention of strokes due to arteriosclerotic disease at the carotid bifurcation. This is a retrospective review of 314 carotid endarterectomies performed at the University Health Center of Pittsburgh. The objectives of the study were to determine if regional anesthesia was a safe technique for carotid endarterectomy and to determine whether the neurologic complications that occurred were embolic or ischemic in origin. In patients who were neurologically intact before operation, the perioperative mortality was 0.88% and the incidence of neurologic complications was 3.1%. This is comparable to the current literature. Observations of the awake patient suggested that half the neurologic deficits that occurred in this series were due to embolization rather than to cerebral ischemia. Further more, the incidence of non-neurologic complications under general anesthesia was 12.9%. Under regional anesthesia, the incidence of non-neurologic complications was 2.8%. The data supports carotid endarterectomy under regional block as safe and reliable method.     

Pharmacological comparison between enflurane and halothane

General pharmacological properties of enflurane (E) and halothane (H) were investigated. Maximum blood concentrations of both drugs reached 30 min after inhalation. E showed lower maximum blood concentration, initial velocity of uptake and shorter half life than H. Neither drug had any effect on neuromuscular junction, but E increased N-M effect of succinylcholine. Both drugs decreased tension of uterine and intestine muscles. Poly- and monosynaptic reflexes were inhibited more by H. ED50's of E and H for intestine muscles. Poly- and monosynaptic reflexes were inhibited more by H. ED50's of E and H for righting reflux were 1.25 and 1.40%, respectively. Tonic and clonic convulsions and death induced by electric shock were inhibited more by E. Almost equal anticonvulsive potency was observed for chemoshocks. Death due to electric and chemoshock was remarkably inhibited by both drugs. Spontaneous EEG was altered in a different manner, although flattened with spikes at 4% concentration of both drugs. E altered rhythmicity of recruiting response and both drugs inhibited this response. H inhibited more remarkably the augmenting response and E inhibited the arousal response. E increased negative potentials of the primary response evoked by sensory stimulation, while H decreased these potentials. Both drugs completely inhibited the secondary response.