bluuebunny/crossref_metadata_2025 huggingface dataset:
Susceptibility to Upper Airway Obstruction during Partial Neuromuscular Block
Authors: D'Honneur Gilles , Lofaso Frederic , Drummond Gordon B. , Rimaniol Jean-Marc , Aubineau Jean V. , Harf Alain , Duvaldestin Philippe
Published: November 2003

Background

Airway obstruction after anesthesia may be caused or exaggerated by residual neuromuscular block, with loss of muscle support for collapsible upper airway structures.

Methods

Six male volunteers were studied before treatment, during stable partial neuromuscular block with vecuronium at a mean train-of-four (TOF) ratio of 50% (95% CI, 36-61%), and after reversal by neostigmine. Catheter-mounted transducers were placed in the pharynx and esophagus to estimate, respectively, the upper airway resistance, and the work of breathing (calculated as the time integral of the inspiratory pressure developed by the respiratory muscles, esophageal pressure time product) during quiet breathing, during breathing 5% carbon dioxide, and while breathing with an inspiratory resistor. Breathing with pressure at the airway opening held at pressures from -5 to 40 cm H2O were also tested to assess airway collapsibility.

Results

Although breathing through a resistor increased upper airway resistance from 1.2 (0.67, 1.72) cm H2O x l(-1) x s to 2.5 (1.32, 3.38) cm H2O x l(-1) x s, and carbon dioxide stimulation reduced resistance to 0.8 (0.46, 1.33) cm H2O x l(-1) x s, no effect of partial neuromuscular block (mean TOF ratio, 52%) on upper airway properties could be shown.

Conclusions

Neuromuscular block with a TOF ratio of 50% can be present yet clinically difficult to detect in patients recovering from anesthesia. This degree of block has no effect on airway patency in volunteers, even during challenge. Airway obstruction during recovery from anesthesia thus is more likely to be caused by residual effects of general anesthetic agents or centrally acting analgesics, either alone or perhaps in concert with residual neuromuscular block.
In Vivo Effects of Dexmedetomidine on Laser-Doppler Flow and Pial Arteriolar Diameter
Authors: Ganjoo Pragati , Farber Neil E. , Hudetz Antal , Smith Jeremy J. , Samso Enric , Kampine John P. , Schmeling William T.
Published: November 2003

Background

The alpha2-adrenergic agonist dexmedetomidine alters global cerebral blood flow (CBF). However, few studies have investigated the action of dexmedetomidine on the cerebral microcirculation. This investigation examined the effects of dexmedetomidine on (1) regional CBF in the rat cerebral cortex using laser-Doppler flowmetry and (2) on pial arteriolar diameter.

Methods

Halothane-anesthetized rats were fitted with instruments to measure CBF as determined by laser-Doppler flow (CBFldf) or to measure pial arteriolar diameter by preparing a cranial hollow deepened until a translucent plate of skull remained, thereby maintaining the integrity of the cranial vault. In both groups, 20 microg/kg dexmedetomidine was infused intravenously. Thirty minutes later, the mean arterial pressure was restored to control values with an infusion of phenylephrine (0.5 to 5 microg/kg/min).

Results

Administration of dexmedetomidine was associated with decreases in end-tidal and arterial carbon dioxide. The CBFldf and pial arteriolar diameter were measured during normocapnia (controlled carbon dioxide) and during dexmedetomidine-induced hypocapnia. Intravenous administration of dexmedetomidine significantly decreased systemic arterial pressure concurrent with a decrease in CBFldf (22% in normocapnic animals, 36% in hypocapnic animals). Restoration of mean arterial pressure increased CBFldf in normocapnic but not in hypocapnic animals. Similarly, dexmedetomidine significantly reduced pial vessel diameter in both normocapnic (9%) and hypocapnic animals (17%). However, vessel diameters remained decreased in the normocapnic and hypocapnic animals after the mean arterial pressure was restored.

Conclusions

These results suggest a modulation of cerebral vascular autoregulation by dexmedetomidine which may be mediated, in part, by alterations in carbon dioxide. Dexmedetomidine may have a direct action on the cerebral vessels to reduce the CBF during normo- or hypocapnia. The differences between CBFldf and pial arteriole responses to restoration of mean arterial pressure may reflect the difference in measurement techniques because laser-Doppler measurements reflect the net effect of several arterial segments on microvascular perfusion, whereas diameter measurements specifically examined individual pial arterioles, suggesting that dexmedetomidine vasoconstriction in the cerebral vasculature may be differentially and regionally mediated.
Inhibitory Effects of Propofol on Intracellular Signaling by Endothelin-1 in Aortic Smooth Muscle Cells
Authors: Tanabe Kumiko , Kozawa Osamu , Kaida Takehiro , Matsuno Hiroyuki , Niwa Masayuki , Ohta Shuichiro , Dohi Shuji , Uematsu Toshihiko
Published: November 2003

Background

Blood pressure decreases when propofol is administered. However, the exact mechanism underlying the vascular effects of propofol has not yet been elucidated. Endothelin produced by vascular endothelial cells is a potent vasoactive peptide that elicits prolonged contraction of vascular smooth muscle cells. The effects of propofol on endothelin-1-induced intracellular signaling in an aortic smooth muscle cell line, A10 cells, were examined.

Methods

Cultured A10 cells were pretreated with propofol for 20 min and then stimulated with endothelin-1. The effect of propofol on the endothelin-1-induced Ca2+ influx into A10 cells was evaluated by measuring intracellular 45Ca2+. The effects of propofol on the endothelin-1-induced activation of phosphatidylinositol-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing phospholipase D were evaluated by measuring the formation of inositol phosphates and choline, respectively. The effect of propofol on endothelin-1 binding to its receptor was determined by an [125I] endothelin-1-binding assay.

Results

Propofol inhibited the endothelin-1-induced Ca2+ influx, but this was significant only at supuraclinical concentrations. The endothelin-1-stimulated formation of inositol phosphates was significantly suppressed by propofol. However, propofol had no effect on the formation of inositol phosphates induced by NaF, an activator of heterotrimeric guanosine triphosphate (GTP)-binding proteins. Propofol inhibited the endothelin-1-induced formation of choline. Propofol had no effect on the binding of endothelin-1 to its receptor.

Conclusions

These results suggest that propofol inhibits endothelin-1-induced intracellular signaling in vascular smooth muscle cells. The inhibitory effect of propofol might be exerted at a point between the endothelin-1 receptor and its GTP-binding protein. However, because all significant effects are observed at high concentrations, clinical relevance is unclear.
Fructose-1,6-Bisphosphate Preserves Adenosine Triphosphate but Not Intracellular pH during Hypoxia in Respiring Neonatal Rat Brain Slices
Authors: Espanol Maryceline T. , Litt Lawrence , Hasegawa Koh , Chang Lee-Hong , Macdonald Jeffrey M. , Gregory George , James Thomas L. , Chan Pak H.
Published: November 2003

Background

Fructose-1,6-bisphosphate (FBP) sometimes provides substantial cerebral protection during hypoxia or ischemia. 31P/1H nuclear magnetic resonance spectroscopy of cerebrocortical slices was used to study the effects of FBP on hypoxia-induced metabolic changes. In addition, 13C-labeled glucose was administered and 13C nuclear magnetic resonance spectroscopy was used to search for FBP-induced modulations in glycolysis and the pentose-phosphate pathway.

Methods

In each experiment, 80 slices (350 microm) obtained from ten 7-day-old Sprague-Dawley rat litter mates were placed together in a 20-mm nuclear magnetic resonance tube, perfused, and subjected to 30 min of hypoxia (PO2 < 3 mmHg). Nine experiments were performed, with n = 3 in each of three groups: (1) no treatment with FBP; (2) 60 min of prehypoxia treatment with FBP (2 mM); and (3) 60 min of posthypoxia treatment with FBP (2 mM). 31P/1H Interleaved nuclear magnetic resonance spectra at 4.7 T provided average adenosine triphosphate, intracellular pH, and lactate. Cresyl violet stains of random slices taken at predetermined time points were studied histologically. Some experiments had [2-13C]glucose in the perfusate. Slices from these studies were frozen for perchloric acid extraction of intracellular metabolites and studied with high-resolution 13C nuclear magnetic resonance spectroscopy at 11.75 T.

Results

With no pretreatment with FBP, hypoxia caused an approximately 50% loss of adenosine triphosphate, an approximately 700% increase in lactate, and a decrease in intracellular pH to approximately 6.4. Pretreatment with FBP resulted in no detectable loss of adenosine triphosphate, no increase in lactate, and minimal morphologic changes but did not alter decreases in intracellular pH. 13C Nuclear magnetic resonance spectra of extracted metabolites showed that pretreatment caused accumulation of [1-13C]fructose-6-phosphate, an early pentose-phosphate pathway metabolite. Posthypoxic treatment with FBP had no effects compared with no treatment.

Conclusions

During severe hypoxia, pretreatment with FBP completely preserves adenosine triphosphate and almost completely preserves cell morphology but does not alter hypoxia-induced decreases in intracellular pH. Pretreatment also substantially augments the flux of glucose into the pentose-phosphate pathway.
Bayesian Modeling of Muscle Biopsy Contracture Testing for Malignant Hyperthermia Susceptibility
Authors: Loke Julian C. P. , MacLennan David H.
Published: November 2003

Background

Phenotyping malignant hyperthermia (MH) by contracture testing has a low but quantifiable degree of inaccuracy, measured by its sensitivity and specificity. Quantifying the limitations inherent in diagnostic testing for MH can help resolve issues in clinical practice, such as the interpretation of a negative test and the apparent lack of complete genetic linkage to RYR1.

Methods

Bayesian models, mathematical descriptions of the outcome of diagnostic testing, were constructed. The inputs to the model include patient factors, summarized in a single number called pretest probability (PTP), and sensitivity and specificity that specify the accuracy of the entire test process. The outputs of the model include positive predictive value (PPV) and negative predictive value (NPV), which are numeric expressions of diagnostic certainty of positive and negative test results. A special case was constructed for equivocal results.

Results

The PPV, NPV, and efficiency of contracture testing for MH are functions of PTP, sensitivity, and specificity. The NPV is high for all clinical PTP, whereas PPV is clinically useful for moderate to high PTP.

Conclusions

Diagnostic contracture testing for MH is clinically useful because of high NPV and can exclude MH with near certainty. For MH probands, the clinical grading scale for MH may guide PTP estimation, whereas for relatives of probands, PTP is a function of kinship to a known MH-susceptible relative. A sequential testing strategy optimizes diagnostic information by maximizing PTP within a pedigree. Incomplete testing of parents of an MH susceptible child can pose a significant risk of false-negative results for the untested parent. Even with optimal pedigree testing strategies, the PPV drift effect results in a considerable source of phenotypic uncertainty for genetic linkage studies.
Transient Neurologic Symptoms after Spinal Anesthesia with Mepivacaine and Lidocaine
Authors: Liguori Gregory A. , Zayas Victor M. , Chisholm Mary F.
Published: November 2003

Background

Spinal anesthesia with lidocaine is ideal for ambulatory surgery because of its short duration of action. However, transient neurologic symptoms (TNS) occur in 0-40% of patients. The incidence of TNS with mepivacaine, which has a similar duration of action, is unknown.

Methods

Sixty ambulatory patients undergoing knee arthroscopy received spinal anesthesia in a randomized, double-blinded manner, with either 45 mg 1.5% mepivacaine or 60 mg 2% lidocaine. An L3-L4 midline approach was used with a 27-gauge Whitacre needle and a 20-gauge introducer. The local anesthetic was injected over approximately 30 s with the aperture of the Whitacre needle in a cephalad direction. Two to 4 days after operation, each patient was questioned about the development of TNS. In addition, the two groups were compared for time to regression of sensory and motor blockade and time to discharge milestones.

Results

Three patients receiving lidocaine were lost to follow-up. None of the 30 patients in the mepivacaine group developed TNS, whereas 6 of 27 (22%) in the lidocaine group did (P = 0.008). Time to regression to the L5 sensory level and to complete resolution of motor block were similar in both groups. The times to discharge milestones were also comparable.

Conclusions

The incidence of TNS is greater with 2% lidocaine than with 1.5% mepivacaine for patients having unilateral knee arthroscopy under spinal anesthesia. Mepivacaine seems to be a promising alternative to lidocaine for outpatient surgical procedures because of its similar duration of action. Further studies are warranted to determine the optimal dose of intrathecal mepivacaine for ambulatory surgery and the incidence of TNS with other doses and concentrations of intrathecal mepivacaine.
Transient Neurologic Symptoms after Spinal Anesthesia
Authors: Hampl Karl F. , Heinzmann-Wiedmer Sidonie , Luginbuehl Igor , Harms Christoph , Seeberger Manfred , Schneider Markus C. , Drasner Kenneth
Published: November 2003

Background

Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs.

Methods

Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure.

Results

Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05).

Conclusions

Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs.
Electroencephalographic Derivatives as a Tool for Predicting the Depth of Sedation and Anesthesia Induced by Sevoflurane
Authors: Katoh Takasumi , Suzuki Akira , Ikeda Kazuyuki
Published: November 2003

Background

The electroencephalogram (EEG) has been evaluated as a tool for measuring depth of anesthesia, but the use of the EEG monitoring is still controversial. The current study was designed to evaluate the accuracy of three EEG parameters and anesthetic concentration for predicting depth of sedation and anesthesia during sevoflurane anesthesia

Methods

One low and one high equilibrated concentration ranging from 0.2-1.8% were assigned randomly and administered consecutively to 69 patients. The bispectral index (BIS; version 3.2), 95% spectral edge frequency (SEF), and median power frequency (MPF) were obtained from a bipolar frontomastoid (Fp1-A1, Fp2-A2) montage using an EEG monitor. Sedation was assessed using the responsiveness portion of the observer's assessment of alertness-sedation scale. In the second phase of the study, the 47 patients who were scheduled to have skin incisions were observed for purposeful movement in response to skin incision at sevoflurane concentrations between 1.6% and 2.4%. The relation among BIS, 95% SEF, MPF, sevoflurane concentration, sedation score, and movement or no movement after skin incision, was determined. Prediction probability values for EEG parameters and sevoflurane concentration to predict depth of sedation and anesthesia were also calculated.

Results

The BIS and sevoflurane concentration correlated closely with the sedation score. Both 95% SEF and MPF changed significantly but biphasically with increasing sedation. The prediction probability values for BIS and sevoflurane concentration were 0.966 and 0.945, respectively, indicating a high predictive performance for depth of sedation. No EEG parameters predicted movement after skin incision better than chance alone.

Conclusions

Parameters derived from EEG, such as BIS, and 95% SEF are reliable guides to the depth of sedation, but not to the adequacy of anesthesia level for preventing movement during sevoflurane anesthesia.
Hypoxia Causes Apnea during Epidural Anesthesia in Rabbits
Authors: Hogan Quinn H. , Amuzu John , Clifford Philip S. , Bosnjak Zeljko J. , Kampine John P.
Published: November 2003

Background

Although pulmonary function is minimally changed by neuraxial blockade in most cases, ventilatory arrest may ensue in rare cases. The authors examined the mechanism of apnea in a rabbit model of sudden ventilatory arrest during the combination of epidural anesthesia and hypoxia.

Methods

Rabbits were studied during alpha-chloralose sedation and spontaneous ventilation through a tracheostomy tube. Heart rate and mean arterial pressure were monitored by intraarterial cannulation. Respiratory rate and tidal volume were measured by pneumotachograph. Responses were recorded during administration of oxygen at inspired oxygen concentrations of 11% for 2.5 min and 0% for 40 s, before and after either thoracolumbar epidural blockade (0.4 ml/kg lidocaine, 1.5%) or intramuscular lidocaine (15 mg/kg). In a third group of animals, epinephrine was given intravenously during epidural blockade to return mean arterial pressure to baseline values before hypoxia. In a fourth group of animals, which did not get lidocaine, sympathetic blockade and hypotension were produced with intravenously administered trimethaphan rather than epidural blockade.

Results

Thoracolumbar epidural anesthesia decreased mean arterial pressure from 76 +/- 4 mmHg (mean +/- SE) to 42 +/- 2 mmHg. Apnea during hypoxia occurred in 90% of these animals (nine of ten) but in only 11% of animals (one of nine) after intramuscularly administered lidocaine (P < 0.01). Treatment of epidural hypotension with epinephrine prevented apnea (zero of nine animals). Apnea during hypoxia occurred in 50% (three of six) of animals given trimethaphan. Apnea in all groups was sudden in onset, with no preceding decreases in respiratory rate or tidal volume.

Conclusions

Epidural anesthesia results in a narrowed margin of safety for oxygen delivery to the brain and predisposes subjects to ventilatory arrest during hypoxia. This results from the combined effects of decreased blood oxygen content, which is due to decreased inspired oxygen concentration superimposed on circulatory depression due to neural blockade.
Ketamine Inhibits Monoamine Transporters Expressed in Human Embryonic Kidney 293 Cells
Authors: Nishimura Mitsuhiro , Sato Kohji , Okada Tomoya , Yoshiya Ikuto , Schloss Patrick , Shimada Shoichi , Tohyama Masaya
Published: November 2003

Background

Ketamine has been characterized as having psychotomimetic and sympathomimetic effects. These symptoms have raised the possibility that ketamine affects monoaminergic neurotransmission. To elucidate the relation between ketamine and monoamine transporters, the authors constructed three cell lines that stably express the norepinephrine, dopamine, and serotonin transporters and investigated the effects of ketamine on these transporters.

Methods

Human embryonic kidney cells were transfected using the Chen-Okayama method with the human norepinephrine, rat dopamine, and rat serotonin transporter cDNA subcloned into the eukaryotic expression vector. Using cells stably expressing these transporters, the authors investigated the effects of ketamine on the uptake of these compounds and compared them with those of pentobarbital.

Results

Inhibition analysis showed that ketamine significantly inhibited the uptake of all three monoamine transporters in a dose-dependent manner. The Ki (inhibition constant) values of ketamine on the norepinephrine, dopamine, and serotonin transporters were 66.8 microM, 62.9 microM, and 162 microM, respectively. Pentobarbital, a typical general anesthetic agent with no psychotic symptoms, did not affect the uptake of monoamines, however. Further, neither the glycine transporter 1 nor the glutamate/aspartate transporter was affected by ketamine, indicating that ketamine preferentially inhibits monoamine transporters.

Conclusions

Ketamine inhibited monoamine transporters expressed in human embryonic kidney cells in a dose-dependent manner. This result suggests that the ketamine-induced inhibition of monoamine transporters might contribute to its psychotomimetic and sympathomimetic effects through potentiating monoaminergic neurotransmission.
Anesthesia Sensitivity in Mice that Lack the β3 Subunit of the γ-Aminobutyric Acid Type A Receptor
Authors: Quinlan Joseph J. , Homanics Gregg E. , Firestone Leonard L.
Published: November 2003

Background

The mammalian gamma-aminobutyric acid type A (GABA(A)) receptor, a likely target of anesthetic action, exhibits remarkable subunit heterogeneity. In vitro expression studies suggest that there is subunit specificity to anesthetic responses at the GABA(A) receptor. The authors tested whether genetically engineered mice that lack the beta3 subunit of the GABA(A) receptor differed in their sensitivities to several general anesthetic agents.

Methods

Median effective concentrations for loss-of-righting reflex and tail clamp/withdrawal for enflurane and halothane were determined in mice with and without the beta3 gene and gene product. Sleep time was measured after intraperitoneal injection of pentobarbital, ethanol, etomidate, and midazolam.

Results

Null allele mice (beta3 -/-) did not differ from wild-type mice (beta3 +/+) in the obtunding response to enflurane and halothane but were significantly more resistant to enflurane (null allele half-effect concentrations [EC50] of 2.59 +/- 0.10 vs. wild-type EC50 of 2.06 +/- 0.12 atm %, P < 0.001) and halothane (null allele EC50 of 1.73 +/- 0.04 vs. wild-type EC50 of 1.59 +/- 0.05 atm %, P = 0.01) as determined by tail clamp response. Wild-type and null allele mice exhibited divergent responses to other sedative agents active at the GABA(A) receptor. No differences were noted in sleep times after administration of pentobarbital and ethanol, but null allele mice were more resistant to etomidate (null allele EC50 of 17.8 +/- 1.9 min vs. wild-type EC50 of 26.2 +/- 2.4 min, P < 0.02) and midazolam (null allele EC50 of 14.2 +/- 7.8 min vs. wild-type EC50 of 41.3 +/- 10.4 min, P < 0.05).

Conclusions

The beta3 subunit of the GABA(A) receptor appears to be important in the mediation of the immobilizing (tail clamp) but not obtunding (loss-of-righting reflex) effects of the volatile anesthetic agents enflurane and halothane. These data support the hypotheses that separate components of the anesthetic state are mediated via different central nervous system loci; that the GABA(A) receptor is a likely target for the immobilizing response to volatile anesthetic agents; and that the beta3 subunit plays a direct or indirect role in the mediation of this response. Absence of the beta3 subunit appears to attenuate the obtunding effect of midazolam and etomidate but appears not to alter the obtunding effect of pentobarbital, enflurane, and halothane, suggesting that these anesthetic agents produce hypnosis by different specific molecular mechanisms.
Propofol and Ketamine Only Inhibit Intracellular Ca2+Transients and Contraction in Rat Ventricular Myocytes at Supraclinical Concentrations
Authors: Kanaya Noriaki , Murray Paul A. , Damron Derek S.
Published: November 2003

Background

The cellular mechanisms that mediate the cardiodepressant effects of intravenous anesthetic agents remain undefined. The objective of this study was to elucidate the direct effects of propofol and ketamine on cardiac excitation-contraction coupling by simultaneously measuring intracellular calcium concentration ([Ca2+]i) and shortening in individual, field-stimulated ventricular myocytes.

Methods

Freshly isolated rat ventricular myocytes were loaded with the Ca2+ indicator, fura-2, and placed on the stage of an inverted fluorescence microscope in a temperature-regulated bath. [Ca2+]i and myocyte shortening (video edge detection) were monitored simultaneously in individual cells that were field-stimulated at 0.3 Hz.

Results

Baseline [Ca2+]i (mean +/- SEM) was 80 +/- 12 nM, and resting cell length was 112 +/- 2 microm. Field stimulation increased [Ca2+]i to 350 +/- 23 nM, and the myocytes shortened by 10% of diastolic cell length. Both intravenous anesthetic agents caused dose-dependent decreases in peak [Ca2+]i and shortening. At 300 microM, propofol prolonged time to peak concentration and time to 50% recovery for [Ca2+]i and shortening. In contrast, changes in time to peak concentration and time to 50% recovery in response to ketamine were observed only at the highest concentrations. Neither agent altered the amount of Ca2+ released from intracellular stores in response to caffeine. Propofol but not ketamine, however, caused a leftward shift in the dose-response curve to extracellular Ca2+ for shortening, with no concomitant effect on peak [Ca2+]i.

Conclusions

These results indicate that both intravenous anesthetic agents have a direct negative inotropic effect, which is mediated by a decrease in the availability of [Ca2+]i. Propofol but not ketamine may also alter sarcoplasmic reticulum Ca2+ handling and increase myofilament Ca2+ sensitivity. The effects of propofol and ketamine are primarily apparent at supraclinical concentrations, however.
Isoflurane Alters Shivering Patterns and Reduces Maximum Shivering Intensity
Authors: Ikeda Takehiko , Kim Jin-Soo , Sessler Daniel I. , Negishi Chiharu , Turakhia Minang , Jeffrey Renee
Published: November 2003

Background

Shivering can be characterized by its threshold (triggering core temperature), gain (incremental intensity increase with further core hypothermia), and maximum response intensity. Isoflurane produces a clonic muscular activity that is not a component of normal shivering. To the extent that clonic activity is superimposed on normal thermoregulatory shivering, the gain of shivering might be increased during isoflurane anesthesia. Conversely, volatile anesthetics decrease systemic oxygen consumption and peripherally inhibit skeletal muscle strength, which might limit maximum intensity despite central activation. The purpose of the present study was, therefore, to evaluate the effect of isoflurane shivering patterns and the gain and maximum intensity of shivering.

Methods

Ten volunteers were each studied in two separate protocols: (1) control (no drug) and (2) 0.7% end-tidal isoflurane. On each day, the mean skin temperature was maintained at 31 degrees C. Core temperature was then reduced by infusion of cold fluid until shivering intensity no longer increased. The core temperature triggering the initial increase in oxygen consumption defined the shivering threshold. The gain of shivering was defined by the slope of the core temperature versus oxygen consumption regression. Pectoralis and quadriceps electromyography was used to evaluate anesthetic-induced facilitation of clonic (5-7 Hz) muscular activity.

Results

Isoflurane significantly decreased the shivering threshold from 36.4 +/- 0.3 to 34.2 +/- 0.8 degrees C. The increase in oxygen consumption was linear on the control day and was followed by sustained high-intensity activity. During isoflurane administration, shivering was characterized by bursts of intense shivering separated by quiescent periods. Isoflurane significantly increased the gain of shivering (as calculated from the initial increase), from -684 +/- 266 to -1483 +/- 752 ml x min(-1) x degrees C(-1). However, isoflurane significantly decreased the maximum intensity of shivering, from 706 +/- 144 to 489 +/- 80 ml/min. Relative electromyographic power in frequencies associated with clonus increased significantly when the volunteers were given isoflurane.

Conclusions

These data indicate that isoflurane anesthesia markedly changes the overall pattern of shivering during progressive hypothermia from a linear increase to an unusual saw-tooth pattern. They further suggest that clonic muscular activity combines with shivering to increase the initial gain of shivering during isoflurane anesthesia, but that isoflurane peripherally inhibits the maximum expression of shivering.
Correlation of Regional Cerebral Blood Flow with Ischemic Electroencephalographic Changes during Sevoflurane-Nitrous Oxide Anesthesia for Carotid Endarterectomy
Authors: Grady Robert E. , Weglinski Margaret R. , Sharbrough Frank W. , Perkins William J.
Published: November 2003

Background

Carotid endarterectomy necessitates temporary unilateral carotid artery occlusion. Critical regional cerebral blood flow (rCBF) has been defined as the rCBF below which electroencephalographic (EEG) changes of ischemia occur. This study determined the rCBF50, the rCBF value at which 50% of patients will not demonstrate EEG evidence of cerebral ischemia with carotid cross-clamping.

Methods

Fifty-two patients undergoing elective carotid endarterectomy were administered 0.6-1.2% (0.3-0.6 minimum alveolar concentration) sevoflurane in 50% nitrous oxide (N2O). A 16-channel EEG was used for monitoring. The washout curves from intracarotid 133Xenon injections were used to calculate rCBF before and at the time of carotid occlusion by the half-time (t(1/2)) technique. The quality of the EEG with respect to ischemia detection was assessed by an experienced electroencephalographer.

Results

Ischemic EEG changes developed in 5 of 52 patients within 3 min of carotid occlusion at rCBFs of 7, 8, 11, 11, and 13 ml x 100 g(-1) x min(-1). Logistic regression analysis was used to calculate an rCBF50 of 11.5 +/- 1.4 ml x 100 g(-1) x min(-1) for sevoflurane. The EEG signal demonstrated the necessary amplitude, frequency, and stability for the accurate detection of cerebral ischemia in all patients within the range of 0.6-1.2% sevoflurane in 50% N2O.

Conclusions

The rCBF50 of 0.6-1.2% sevoflurane in 50% N2O, as determined using logistic regression analysis, is 11.5 +/- 1.4 ml 100 g(-1) x min(-1). Further, in patients anesthetized in this manner, ischemic EEG changes due to carotid occlusion were accurately and rapidly detected.
Inhibition of Presynaptic Sodium Channels by Halothane
Authors: Ratnakumari Lingamaneni , Hemmings Hugh C.
Published: November 2003

Background

Recent electrophysiologic studies indicate that clinical concentrations of volatile general anesthetic agents inhibit central nervous system sodium (Na+) channels. In this study, the biochemical effects of halothane on Na+ channel function were determined using rat brain synaptosomes (pinched-off nerve terminals) to assess the role of presynaptic Na+ channels in anesthetic effects.

Methods

Synaptosomes from adult rat cerebral cortex were used to determine the effects of halothane on veratridine-evoked Na+ channel-dependent Na+ influx (using 22Na+), changes in intrasynaptosomal [Na+] (using ion-specific spectrofluorometry), and neurotoxin interactions with specific receptor sites of the Na+ channel (by radioligand binding). The potential physiologic and functional significance of these effects was determined by measuring the effects of halothane on veratridine-evoked Na+ channel-dependent glutamate release (using enzyme-coupled spectrofluorometry).

Results

Halothane inhibited veratridine-evoked 22Na+ influx (IC50 = 1.1 mM) and changes in intrasynaptosomal [Na+] (concentration for 50% inhibition [IC50] = 0.97 mM), and it specifically antagonized [3H]batrachotoxinin-A 20-alpha-benzoate binding to receptor site two of the Na+ channel (IC50 = 0.53 mM). Scatchard and kinetic analysis revealed an allosteric competitive mechanism for inhibition of toxin binding. Halothane inhibited veratridine-evoked glutamate release from synaptosomes with comparable potency (IC50 = 0.67 mM).

Conclusions

Halothane significantly inhibited Na+ channel-mediated Na influx, increases in intrasynaptosomal [Na+] and glutamate release, and competed with neurotoxin binding to site two of the Na+ channel in synaptosomes at concentrations within its clinical range (minimum alveolar concentration, 1-2). These findings support a role for presynaptic Na+ channels as a molecular target for general anesthetic effects.
Volatile Anesthetic Agents and Vascular Communication in the Microcirculation of the Hamster Cheek Pouch
Authors: Satitpunwaycha Patricia , Rivers Richard J.
Published: November 2003

Background

There is communication between tissue and the vascular network involved in regulating distribution of blood flow. Signals generated by the tissue are communicated upstream to create a coordinated network response in unison with other controllers of blood flow, such as myogenic and flow-dependent responses.

Methods

This vascular communication was modeled with the microapplication of methacholine (10(-4) M) or potassium chloride solution (KCl; 100 mM) to arterioles (40-60 microm in diameter) of the cheek pouch of anesthetized hamsters and viewed with videomicroscopy. Local and conducted (500 microm upstream) responses were measured. Halothane or isoflurane (1%, 2%, and 3%) was equilibrated with the superfusion solution and applied to the entire tissue. Responses to KCl and methacholine were then repeated in the presence of an anesthetic agent.

Results

Halothane and isoflurane increased the resting diameter of the arterioles. They also decreased the methacholine-initiated dilations. To test for the effects of increased resting diameter on the dilations, 0%, 5% and 10% oxygen alone was applied to the pouch to alter the tone, and the methacholine responses were repeated. The dilations decreased with oxygen-induced increases in resting diameter, but the conducted dilation decreased to a lesser extent than was seen with the volatile anesthetic agents. Neither halothane nor isoflurane decreased constrictions caused by KCl.

Conclusions

Decreased methacholine-initiated conducted dilations caused by halothane and isoflurane were not due to decreases in cell-cell communication because KCl conducted responses persisted. Therefore, cell-cell vascular communication appears intact in the presence of clinical concentrations of halothane and isoflurane.
TOK1 Is a Volatile Anesthetic Stimulated K+Channel
Authors: Gray Andrew T. , Winegar Bruce D. , Leonoudakis Dmitri J. , Forsayeth John R. , Yost Spencer C.
Published: November 2003

Background

Volatile anesthetic agents can activate the S channel, a baseline potassium (K+) channel, of the marine mollusk Aplysia. To investigate whether cloned ion channels with electrophysiologic properties similar to the S channel (potassium selectivity, outward rectification, and activation independent of voltage) also are modulated by volatile anesthetic agents, the authors expressed the cloned yeast ion channel TOK1 (tandem pore domain, outwardly rectifying K+ channel) in Xenopus oocytes and studied its sensitivity to volatile agents.

Methods

Standard two-electrode voltage and patch clamp recording methods were used to study TOK1 channels expressed in Xenopus oocytes.

Results

Studies with two-electrode voltage clamp at room temperature showed that halothane, isoflurane, and desflurane increased TOK1 outward currents by 48-65% in barium Frog Ringer's perfusate. The concentrations at which 50% potentiation occurred (EC50 values) were in the range of 768-814 microM (0.016-0.044 atm) and had a rank order of potency in atm in which halothane > isoflurane > desflurane. The potentiation of TOK1 by volatile anesthetic agents was rapid and reversible (onset and offset, 1-20 s). In contrast, the nonanesthetic 1,2-dichlorohexafluorocyclobutane did not potentiate TOK1 currents in concentrations up to five times the MAC value predicted by the Meyer-Overton hypothesis based on oil/gas partition coefficients. Single TOK1 channel currents were recorded from excised outside-out patches. The single channel open probability increased as much as twofold in the presence of isoflurane and rapidly returned to the baseline values on washout. Volatile anesthetic agents did not alter the TOK1 single channel current-voltage (I-V) relationship, however, suggesting that the site of action does not affect the permeation pathway of the channel.

Conclusion

TOK1 is a potassium channel that is stimulated by volatile anesthetic agents. The concentrations over which potentiation occurred (EC50 values) were higher than those commonly used in clinical practice (approximately twice MAC).
Desflurane Reduces the Febrile Response to Administration of Interleukin-2
Authors: Negishi Chiharu , Lenhardt Rainer , Sessler Daniel I. , De Witte Jan , Ikeda Takehiko , Kurz Andrea , Lobo Errol
Published: November 2003

Background

Intraoperative fever is relatively rare considering how often pyrogenic causes are likely to be present and how common fever is postoperatively. This low incidence suggests that general anesthesia per se inhibits the normal response to pyrogenic stimulation. The authors therefore tested the hypothesis that desflurane-induced anesthesia produces a dose-dependent inhibition of the febrile response.

Methods

Eight volunteers were studied, each on 3 study days. Each was given an intravenous injection of 50,000 IU/ kg of interleukin-2 (elapsed time, 0 h), followed 2 h later by 100,000 IU/kg. One hour after the second dose, the volunteers were assigned randomly to three doses of desflurane to induce anesthesia: (1) 0.0 minimum alveolar concentration (MAC; control), (2) 0.6 MAC, and (3) 1.0 MAC. Anesthesia continued for 5 h. Core temperatures were recorded from the tympanic membrane. Thermoregulatory vasoconstriction was evaluated using forearm-minus-fingertip skin temperature gradients; shivering was evaluated with electromyography. Integrated and peak temperatures during anesthesia were compared with repeated-measures analysis of variance and Scheffé's F tests.

Results

Values are presented as mean +/- SD. Desflurane reduced the integrated (area under the curve) febrile response to pyrogen, from 7.7 +/- 2.0 degrees C x h on the control day to 2.1 +/- 2.3 degrees C x h during 0.6 MAC and to -1.4 +/- 3.1 degrees C x h during 1.0 MAC desflurane-induced anesthesia. Peak core temperature (elapsed time, 5-8 h) decreased in a dose-dependent fashion: 38.6 +/- 0.5 degrees C on the control day, 37.7 +/- 0.7 degrees C during 0.6 MAC and 37.2 +/- 1.0 degrees C during 1.0 MAC desflurane anesthesia. Rising core temperature was always associated with fingertip vasoconstriction and often with shivering.

Conclusions

Desflurane-induced anesthesia produced a dose-dependent decrease in integrated and peak core temperatures after administration of pyrogen, with 1.0 MAC essentially obliterating fever. Anesthetic-induced inhibition of the pyrogenic response is therefore one reason that fever is an inconsistent clinical response to inflammation during surgery.
A Bronchoscopic, Computer-assisted Examination of the Changes in Dimension of the Infant Tracheal Lumen with Changes in Head Position
Authors: Wheeler Melissa , Roth Andrew G. , Dunham Michael E. , Rae Bronwyn , Cote Charles J.
Published: November 2003

Background

Resuscitation guidelines caution against extreme extension or flexion of an infant's head because tracheal obstruction may occur. No data support this recommendation. The authors therefore examined the dimensions of the tracheal lumen in neutral, extended, and flexed head positions in infants undergoing general endotracheal anesthesia for elective surgery.

Methods

Eighteen healthy full-term infants were studied. A flexible fiberoptic bronchoscope was passed through a previously inserted endotracheal tube and positioned above the cricoid cartilage. Video recordings were taken in each of three head positions. Recordings were analyzed by an investigator blinded to head position. A computer-digitized technique was used to measure anterior-posterior and lateral dimensions and cross-sectional area. Data were analyzed using paired t tests and sign tests.

Results

No significant differences in mean tracheal dimensions with changes in head position were found. No infant had complete tracheal obstruction. Infants were equally as likely to have a small increase as they were to have a small decrease in tracheal dimension with changes in head position.

Conclusions

Despite the belief that infants and neonates have obstruction at the level of the trachea with extreme positions of the head, the authors were unable to demonstrate this phenomenon.
Effects of Ketamine on the Contractility of Failing and Nonfailing Human Heart Muscles In Vitro
Authors: Sprung Juraj , Schuetz Shannon M. , Stewart Robert W. , Moravec Christine S.
Published: November 2003

Background

Induction of anesthesia with ketamine may decrease cardiac output in critically ill patients. The direct effects of ketamine on the failing human myocardium are unknown. This study examined the effects of ketamine on contractility of human failing and nonfailing myocardium in vitro.

Methods

Trabecular muscles were obtained from the left ventricles and right atria of 10 patients with heart failure undergoing transplantation and from the right atria of 14 patients undergoing coronary artery bypass surgery. Muscles were dissected and mounted in a 37 degrees C bath and stimulated at 1 Hz. Isometric contraction variables were recorded before and after addition of ketamine (concentrations between 0.44 and 440.0 microM) to the bath. The effects of ketamine were compared with those of buffer. To test muscle contractility, at the end of each experiment, 1 microM isoproterenol was added.

Results

Ketamine caused a significant dose-dependent decrease in developed tension in nonfailing atrial and failing atrial and ventricular muscles (P < 0.01 for all). In vehicle-treated muscles, developed tension remained stable, and isoproterenol increased developed tension 136% (nonfailing atrial muscles) and 178% (failing atrial and ventricular muscles; P < 0.01). In nonfailing atrial muscle, isoproterenol restored the ketamine-induced decrease in developed tension toward the baseline value. In failing atrial and ventricular muscles exposed to ketamine, isoproterenol did not counteract the ketamine.

Conclusions

Ketamine exerts a direct dose-dependent negative inotropic effect in human heart muscles. The failing myocardium exposed to ketamine has reduced ability to increase contractility even in the presence of increased beta-adrenergic stimulation.
Interactions between Hypothermia and the Latency to Ischemic Depolarization
Authors: Bart Robert D. , Takaoka Seiji , Pearlstein Robert D. , Dexter Franklin , Warner David S.
Published: November 2003

Background

The authors postulated that hypothermic neuroprotection can be attributed to a delayed onset of ischemic depolarization.

Methods

Halothane-anesthetized rats were prepared for near-complete forebrain ischemia. Direct current (DC) potential microelectrodes were placed in hippocampal CA1. The pericranial temperature was maintained at 31 degrees C, 33 degrees C, 35 degrees C, or 37 degrees C (n = 6 per group). Bilateral carotid occlusion with systemic hypotension was initiated for 10 min. The time to onset of the DC shift was recorded. In a second experiment, rats were assigned to 37 degrees C or 31 degrees C for 10 min of ischemia, or to 31 degrees C for 14 min of ischemia (n = 8 per group). These durations of ischemia were defined to allow 9 min of ischemic depolarization in the 37 degrees C-10 min and 31 degrees C-14 min groups. Neurologic and histologic outcomes were examined 7 days later.

Results

Hippocampal CA1 time to depolarization increased with decreasing temperature (P < 0.0001). Time to depolarization was increased by approximately 4 min in the rats maintained at 31 degrees C compared with those at 37 degrees C. Time to repolarization during reperfusion was not affected by temperature. Increasing the duration of ischemia from 10 min to 14 min with the pericranial temperature maintained at 31 degrees C resulted in a duration of depolarization that was equivalent in the 37 degrees C-10 min and 31 degrees C-14 min groups. However, hippocampal CA1 damage was not increased (31 degrees C-10 min = 4 +/- 1% dead neurons; 31 degrees C-14 min = 6 +/- 1% dead neurons, 95% CI, -1% to 3%; 37 degrees C-10 min = 90 +/- 17% dead neurons).

Conclusions

Despite similar durations of DC depolarization, outcome in hypothermic rats was markedly improved compared with normothermic rats. This indicates that hypothermic neuroprotection can be attributed to mechanisms other than the delay in time to onset of ischemic depolarization.
Etomidate Does Not Alter Recovery after Anoxia of Evoked Population Spikes Recorded from the CA1 Region of Rat Hippocampal Slices
Authors: Amadeu Eduarda M. , Abramowicz Elisabeth A. , Chambers Geoffrey , Cottrell James E. , Kass Ira S.
Published: November 2003

Background

Etomidate is an anesthetic agent that reduces the cerebral metabolic rate and causes minimal cardiovascular depression. Its ability to improve recovery after anoxia or ischemia is equivocal. An in vitro neuronal preparation was used to examine the action of etomidate on electrophysiologic and biochemical parameters during and after anoxia.

Methods

The Schaffer collateral pathway was stimulated, and a postsynaptic evoked population spike was recorded from the CA1 pyramidal cell layer of rat hippocampal slices. Etomidate or propylene glycol, its solvent, was present 15 min before, during, and 10 min after anoxia. Adenosine triphosphate, sodium, and potassium concentrations were measured at the end of anoxia in tissue treated with etomidate, propylene glycol, or with no added drugs.

Results

Etomidate did not alter recovery after 6 min of anoxia. The population spikes from untreated slices recovered to 32% of their preanoxic amplitude, and slices treated with 0.5, 3, and 30 microg/ml etomidate recovered to 24%, 35%, and 13%, respectively. Slices treated with propylene glycol, equivalent to that in 3 and 30 microg/ml etomidate, recovered to 46% and 12%, respectively, and this was not significantly different from untreated slices. Etomidate did not attenuate the decrease in adenosine triphosphate concentrations during anoxia. The increase in sodium and the decrease in potassium during anoxia were significantly attenuated by 30 but not by 3 microg/ml etomidate.

Conclusions

A range of etomidate concentrations did not significantly alter recovery of the evoked population spike after anoxia in rat hippocampal slices. A high concentration of etomidate did attenuate the increase in sodium and the decrease in potassium during anoxia.