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Cardiovascular effects of plasma levels of thiopental necessary for anesthesia.

The cardiovascular effects of plasma levels of thiopental necessary for anesthesia were studied using systolic time intervals (STI). In ten healthy patients anesthesia was induced with thiopental, 2-2.5 mg/kg, intravenously, and maintained with an infusion of 1-1.5 mg/kg/min. STI and thiopental plasma levels were measured before induction and when corneal reflex and trapezius muscle response, indicators of anesthetic depth equivalent to response to surgical stimulation, were lost. Significant changes included: an increase in heart rate with induction of anesthesia; a decrease in 1/pre-ejection period2--indexed for heart rate (1/PEP2-I) at loss of corneal reflex; a decrease in systolic blood pressure and 1/PEP2-I at loss of trapezius muscle response. No other variable was significantly different from control. Control values for STI were in the high-normal range, indicating some sympathetic stimulation. With induction of anesthesia these values decreased to a normal range. Free and total plasma levels were 5.4 and 37.6 microgram/ml at loss of corneal reflex; 6.1 and 41.6 microgram/ml at loss of trapezius muscle response. In comparison with other studies, thiopental causes less cardiac depression than inhalational agents at approximately the same anesthetic depth. It is concluded from this study in healthy patients that plasma levels of thiopental producing surgical anesthesia result in minimal cardiac depression as determined by systolic time intervals.

Adult

Intravenous lidocaine reduces the propofol EC50 for loss of consciousness and intraoperative anesthetic consumption in gynecological laparoscopy: A randomized controlled trial.

BACKGROUND: Intravenous lidocaine reduces propofol requirements and procedure-related adverse events. OBJECTIVES: The study aimed to test whether intravenous lidocaine would reduce the effect-site concentration of propofol required to achieve loss of consciousness and decrease propofol consumption during total intravenous anesthesia in gynecological laparoscopy. METHODS: This was a prospective, randomized, double-blind, placebo-controlled trial. Sixty patients were randomly allocated to receive either intravenous lidocaine (1.5 mg·kg-¹ bolus) followed by continuous infusion or an equal volume of saline. Propofol was administered via target-controlled infusion starting at an effect-site concentration of 3.5 μg/mL. The concentration was then adjusted in steps of 0.5 μg/mLaccording to Dixon's up-and-down sequential method: decreased if loss of consciousness was achieved, or increased if not. Loss of consciousness was defined as loss of response to verbal commands. The median effective concentration (EC50) of propofol for inducing loss of consciousness was calculated using the Dixon's up-and-down method. General anesthesia was maintained with propofol and remifentanil, guided by state entropy (target 40-60) and surgical pleth index (target 20-50). Drug consumption was normalized to anesthesia duration and body weight. RESULTS: The estimated EC50 of propofol for inducing loss of consciousness was significantly lower in the lidocaine group than in the saline group (3.32 μg/mL, 95% Confidence Interval (CI): 3.04-3.59 vs. 3.89 μg/mL, 95% CI: 3.50-4.28). Under the study protocol, the lidocaine group also required less propofol (8.62 mg·kg-1·h-1, 95% CI: 8.10-9.15 vs. 9.89 mg·kg-1·h-1, 95% CI: 9.05-10.73) and less remifentanil (0.23 μg·kg-1·min-1, 95% CI: 0.21-0.24 vs. 0.27 μg·kg-1·min-1, 95% CI: 0.24-0.30) compared with the saline group. CONCLUSION: Intravenous lidocaine reduced the propofol EC50 for Loss of Consciousness (LOC) and decreased intraoperative propofol and remifentanil consumptions in patients undergoing gynecological laparoscopy. These findings suggest a propofol- and opioid-sparing effect of intravenous lidocaine in this setting, although confirmation in larger multicenter trials is needed.

Humans

[Local anesthesia after percutaneous administration. I].

Local anesthesia of the intact skin is difficult because of the skin barrier to epicutaneous penetration. Using solutions of local anesthetics in organic agents, which have the ability of penetrating the skin without causing irreversible damage and enhancing the percutaneous absorption of all materials dissolved therein, topical anesthesia seems to be attainable. A satisfactory method for determining pain threshold in uninjured skin of animals has been set up. Measurments of the pricking pain threshold have been made by exposing the skin of guinea-pigs to defined mechanical and electrical stimuli. A nociceptive muscle reflex (twitch) has been taken as the index of pain sensation. The suppression of this twitch has been used as an indicator of anesthetic potency. Two methods have been applied with varying parameters: stimulation at a fixed intensity until the pain threshold was reached (duration of anesthetic effect) and stimulation with increasing stimulus strenght until the cutaneous reflex was elicited (intensity or "depth" of anesthesia). The local anesthetic effects of lidocaine, fomocaine and procaine bases were studied, after dissolving them in dimethyl sulfoxide (DMSO), a wellknown carrier for transmembranal application. The duration of local anesthesia measured by electrical stimuli was longer than that obtained with mechanical ones. Differences are discussed. All results indicate that fomocaine (5%) has a greater local anesthetic potency than procaine (5%) but both are less active than lidocaine (5%). No effect could be seen after application of DMSO alone.

Administration, Topical

Monitoring in the operating room: current techniques and future requirements.

Review of a recent lawsuit and study of operating room cardiac arrests reveal that ventilatory problems are a major source of intraoperative morbidity and mortality. Tidal volume and airway gas composition are critical to the anesthesiologist who must determine the depth of an inhalation anesthetic. Yet, current instrumentation does not permit these variables to be measured conveniently. In this paper, current techniques for monitoring cardiovascular physiology are review, and considerable attention is focused on the problem of and the requirements for ventilatory monitoring in the operating room. The high dollar cost of infrequent untoward events is discussed, as well as the additional problem this creates because individual anesthesiologists may receive little positive reinforcement in encouraging the development of more sophisticated monitoring techniques.

Anesthesia

The effect of limb movements on the regulation of depth and rate of breathing.

In anesthetized dogs and rabbits passive or active limb movements (1) shifted to the left the relationship between tidal volume (Vt) and inspiratory time (Ti), (2) lowered the relationship between expiratory time (Te) and Ti and decreased its slope, and (3) increased the output to the inspiratory muscles (Vt/Ti). These effects increased with increasing the frequency of movements. Similar effects were obtained after vagotomy. When the stimulus was started during expiration. Te was shorted in spite of the previous unaffected Ti, Arterial PCO2 during exercise was similar (active movements) or below (passive movements) control value. Since other chemical and physical humoral factors do not seem involved, the whole increase of ventilation should be produced by neurogenic stimuli. The time course of Te, Ti and VT/Ti at the onset and at the offset of limb movements indicates an abrupt and a slow component in the neurogenic drive. A single contraction of the limb during expiration of inspiration affected the timing and the VT/Ti of 3-8 breaths.

Animals

Effect of mechanical factors on the relation between rate and depth of breathing in cats.

In anesthetized tracheotomized cats we compared the time sequence of ventilatory events with neurological events (electrical activity of the diaphragm) during the breathing cycle. We found that under control conditions a phase shift existed between the neurological and the spirometric duration of inspiration, amounting to about 150 ms. This phase shift was increased by increasing the time constant of the respiratory system (resistive loading) and decreased by decreasing it (elastic loading). These phase shifts resulted in a difference in the appreciation of the volume responsible for the termination of inspiration (Hering-Breuer inhibition) because the volume corresponding to the end of the neurological event was somewhat smaller than the final tidal volume reached.

Animals

Antagonism of general anesthesia by naloxone in the rat.

The effect of naloxone, a narcotic antagonist, on the response of animals to painful stimuli during anesthesia was studied. Rats were anesthetized with cyclopropane, halothane, or enflurane in groups of 12. Following induction, inspired anesthetic concentration was gradually reduced to a point at which 35-60 per cent of animals responded to tail clamping. Thereafter the anesthetic concentration was held constant for 30 minutes. Rats in each group then received saline solution or naloxone, 10mg/kg, given intravenously. The response to tail clamping was retested 5 minutes later. In additional experiments EEG's were recorded from rats anesthesized with one of these anesthetics. After a stable light plane of anesthesia had been attained, each animal was given naloxone, 10 mg/kg, iv, and the EEG recorded for an additional 5 minutes. In the tail-clamping experiments, naloxone approximately doubled the number of rats responding during cyclopropane, halothane, or enflurane anesthesia. The EEG patterns of several animals anesthetized with either cyclopropane or halothane changed to patterns consistent with lighter planes of anesthesia after naloxone administration. That naloxone alters the depth of inhalational anesthesia suggests that anesthetics may release an endogenous morphine-like factor (MLF) in the central nervous system.

Anesthesia, General

Effect of halothane and halothane-nitrous oxide on hematocrit and plasma protein concentration in dog and monkey.

Hematocrit and plasma protein concentration in healthy dogs and monkeys (Macaca arctoides) awake and anesthetized with halothane-oxygen and halothane-nitrous oxide oxygen were compared during conditions of spontaneous and controlled ventilation. Both hematocrit and plasma protein concentration decreased within 15 minutes following anesthetic induction. This decrease persisted throughout constant- or variable-depth anesthesia and did not vary appreciably with ventilation, anesthetic dose, or introduction of nitrous oxide. Plasma volume, determined by a dye dilution technique, concomitantly increased. This increase is compatible with the directional changes in hematocrit and plasma protein.

Anesthesia, Inhalation

Anatomical correlates of rhythmical slow wave activity (theta) in the hippocampal formation of the cat.

The topography of spontaneous and hypothalamically induced hippocampal rhythmical slow wave activity (theta) was studied acutely in cats anesthetized with urethane. Tracking and depth profile analysis using microelectrodes showed two amplitude maxima of theta activity approximately 180 degrees out of phase separated by a null zone. One amplitude peak was located in stratum oriens of CA1 (maximum amplitude 1.2 mV) and the other peak in stratum moleculare of the fascia dentata (maximum amplitude 1.9 mV). The null zone was localized to stratum radiatum, just ventral to the CA1 pyramidal cells. The two 'generator' hypothesis of theta activity was discussed in relation to similar findings for other species. Pharmacological results were interpreted as supporting the view that there is an ascending cholinergic input mediating theta in the urethanized cat.

Action Potentials

Effect of anesthetics on mortality and kidney lesions caused by hypotension.

Unanesthetized rats and rats anesthetized with a number of anesthetics were bled according to different bleeding schedules. In rats bled for 60 min against 30-50 mm Hg marked protection against mortality and the occurrence of kidney lesions was obtained with pentobarbital-Na, enflurane, halothane and methoxyflurane. Less protection was provided by diethylether while little or no protection was obtained with ethylurethane, trichloroethylene and ketamine. Protection was afforded by pentobarbital-Na in the dose range of 50 mg/kg to 6.2 mg/kg. Slight protection was afforded by dehydrobenzperidol. If pentobarbital-Na was administered after the bleeding the protection was slight. At bleeding pressures below 30 mm Hg the protective effect disappeared for all anesthetics used. Protection was not correlated with either depth of anesthesia, hypotensive effect or reduction of the maximum bleeding volume. However, a correlation was found between protective effect and the retardation of bleeding and the prolongation of survival time caused by the different anesthetics.

Anesthetics

Pressure, anesthetics, and membrane structure: a spin-probe study.

Fatty acid spin-probe analyses at various depths in the membrane bilayer of intact erythrocytes indicate that compressional effects of pressure and fluidizing effects of lipid-soluble anesthetics are detectable only in hydrated regions of the membrane bilayer. Since current theories of anesthetic action cannot explain these observations, a proposal to do so is outlined.

Anesthetics

Control of depth and frequency of breathing during baroreceptor stimulation in cats.

In 10 tracheotomized anesthetized cats during steady-state inhalation of various concentrations of CO2 and O2, the acute respiratory response to baroreceptor stimulation produced by transient inflation of a balloon placed in the descending aorta was studied. The latter induced a sudden rise in mean arterial pressure, ranging from 62 to 95 mmHg. At all PACO2 levels above 30 mmHg, elevation in arterial pressure was accompanied by an immediate drop in tidal volume (VT) and prolongation of the durations of inspiration (Ti) and total breath (Ttot). Breaths obtained during baroreceptor stimulation fell along the same VT vs. Ti and VT vs. Ttot relationships obtained in the normotensive state, suggesting that the lung volume-related vagal control of Ti and Ttot is unaffected by changes in arterial pressure. Since, for a given change in arterial pressure, a constant reduction in VT was obtained at all PACO2 levels above 30 mmHg, it can be concluded that the interaction between PACO2 and arterial pressure is additive. In three cats, at PACO2 levels below 30 mmHg, aortic obstruction resulted in brief periods of apnea. Following apnea, the control of Ti and Ttot was transiently offset, describing hysteresis pathways on the VT vs. Ti and VT vs. Ttot relationships.

Abdominal Muscles

The effect of metacaine (MS-222) on the activity of the efferent and afferent nerves in the teleost lateral-line system.

1. Free-swimming fish (Tilapia leucosticta and Rutilus rutilus) were used to determine threshold concentrations required for general anesthesia with metacaine (MS-222). The criterion for anesthesia was reached at a concentration of 1:1500 (w/w) with both fish, although the symptoms were somewhat more pronounced in Rutilus. 2. Recordings of efferent spontaneous activity in the lateral-line nerve were used as a measure of the central effect of metacaine during administration in the respiratory stream, as compared with respiration of fresh water. The reduction of activity at the end of a 3-min exposure to the drug was 70%. 3. Maximum recovery (90% of the initial activity) was reached after 30 min application of fresh water. 4. The various efferent impulse types were differentially affected by the anesthetic. 5. Direct recordings from sound-sensitive neurons in the medulla confirm the strong central effect of metacaine. 6. Irrigation of the lateral-line system with anesthetic solution also produced a reduction in afferent spontaneous activity; there was a distinct peripheral effect even at the threshold concentration. 7. Reactions of trigeminal nerve fibers to mechanical stimulation of the skin were reduced after application of a metacaine solution to the skin. This finding confirms the local anesthetic effect of the drug. 8. The anesthetic solution at a given concentration had a greater effect on the CNS than on the peripheral receptors. 9. The implications of the results with respect to the risk of misjudging the depth of general anesthesia are discussed. 10. Because of the complexity of its anesthetic efficacy, it is recommended that metacaine not be used for neurophysiological investigations, but rather that the animals be immobilized by means of muscle relaxants.

Action Potentials

A safe anesthetic for rabbits, using methoxyflurane.

Methoxyflurane was given by inhalation as the sole anesthetic agent to 42 New Zealand white rabbits, with no mortality. The depth of respiration as well as the changes in the color of the ears were monitored constantly. A technique for administering methoxyflurane without intubation is described.

Anesthesia, Inhalation

Enflurane requirement and ventilatory response to carbon dioxide during lidocaine infusion in dogs.

Arterial plasma lidocaine concentration of 1 to 3.5 microgram/ml produced dose-related decreases in enflurane requirement (MAC) ranging from 15 to 37 per cent in dogs. The ventilatory responses to carbon dioxide at comparable depths of anesthesia with enflurane alone and the enflurane-lidocaine combination were measured in each animal and compared. With both anesthetic regimens there were increases in resting arterial carbon dioxide tension (mean maximal increase = 18 torr) and a 69 per cent decrease in the slope of the ventilatory response as depth of anesthesia increased. The effect of the drug interaction appears to be additive, since the ventilatory depression produced by the enflurane-lidocaine combination was no greater than that produced by enflurane alone at equivalent levels of anesthesia.

Anesthesia, General

The morphology of spinocervical tract neurones in the cat.

1. The morphology of physiologically identified spinocervical tract (SCT) neurones was studied using the intracellular injection of Procion dyes in anesthetized and decerebrate cats. 2. Extracellular recordings were made from SCT neurones at depths between 1000 and 2850 mum from the cord surface but neurones were only stained at depths between 1100 and 2400 mum. 3. The dendritic trees of stained SCT neurones were reconstructed in the transverse plane of the spinal cord. All SCT neurones had well developed dorsal dendrites but despite this it is not possible to consider the twenty-two SCT cells in out sample as consituting a morphologically homogenous population. 4. There was no correlation between the form of the dendritic trees and the depth of SCT neurones in the dorsal horn as determined both from measurements from the dorsal grey-white border and the position of cells with respect to the border between Rexed's laminae II and III. 5. Six types of SCT neurones were identified on the basis of the form of their dendritic trees as viewed in the transverse plane: (1) radially symmetrical, (2) semicircular, (3) large elliptical, (4) bilobed, (5) triangular, (6) small elliptical. Each of these types was found only in a certain region across the dorsal horn although any one region could contain more than one type. 6. Spinocervical tract neurones with small elliptical dendritic trees always had receptive fields encompassing part of the hip or thigh and were unique in being located in the lateral portions of the horn. 7. There was no correlation between the morphology of SCT neurones and their excitatory cutaneous inputs, receptive field size, axonal conduction velocity or depth in the dorsal horn.

Action Potentials