bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Thermoregulatory Vasomotion and Ambient Temperature Variation on the Accuracy of Core-temperature Estimates by Cutaneous Liquid-crystal Thermometers
Authors: Ikeda Takehiko , Sessler Daniel I. , Marder Danielle , Xiong Junyu
Published: November 2003

Background

Recently, liquid crystal skin-surface thermometers have become popular for intraoperative temperature monitoring. Three situations during which cutaneous liquid-crystal thermometry may poorly estimate core temperature were monitored: (1) anesthetic induction with consequent core-to-peripheral redistribution of body heat, (2) thermoregulatory vasomotion associated with sweating (precapillary dilation) and shivering (minimal capillary flow), and (3) ambient temperature variation over the clinical range from 18-26 degrees C.

Methods

The core-to-forehead and core-to-neck temperature difference was measured using liquid-crystal thermometers having an approximately 2 degrees C offset. Differences exceeding 0.5 degree C (a 1 degree C) temperature range) were a priori deemed potentially clinically important. Seven volunteers participated in each protocol. First, core-to-peripheral redistribution of body heat was produced by inducing propofol/desflurane anesthesia; anesthesia was then maintained for 1 h with desflurane. Second, vasodilation was produced by warming unanesthetized volunteers sufficiently to produce sweating; intense vasoconstriction was similarly produced by cooling the volunteers sufficiently to produce shivering. Third, a canopy was positioned to enclose the head, neck, and upper chest of unanesthetized volunteers. Air within the canopy was randomly set to 18, 20, 22, 24, and 26 degrees C.

Results

Redistribution of body heat accompanying induction of anesthesia had little effect on the core-to-forehead skin temperature difference. However, the core-to-neck skin temperature gradient decreased approximately 0.6 degree C in the hour after induction of anesthesia. Vasomotion associated with shivering and mild sweating altered the core-to-skin temperature difference only a few tenths of a degree centigrade. The absolute value of the core-to-forehead temperature difference exceeded 0.5 degree C during approximately 35% of the measurements, but the difference rarely exceeded 1 degree C. The core-to-neck temperature difference typically exceeded 0.5 degree C and frequently exceeded 1 degree C. Each 1 degree C increase in ambient temperature decreased the core-to-fore-head and core-to-neck skin temperature differences by less than 0.2 degree C.

Conclusions

Forehead skin temperatures were better than neck skin temperature at estimating core temperature. Core-to-neck temperature differences frequently exceeded 1 degree C (a 2 degrees C range), whereas two thirds of the core-to-forehead differences were within 0.5 degree C. The core-to-skin temperature differences were, however, only slightly altered by inducing anesthesia, vasomotor action, and typical intraoperative changes in ambient temperature.
Recovery of Consciousness after Thiopental or Propofol
Authors: Flaishon R. , Windsor A. , Sigl J. , Sebel P. S.
Published: November 2003

Background

Currently, there exists no effective monitor that can predict the probability of a patient being conscious during general anesthesia. The electroencephalogram-derived bispectral index (BIS) is a promising new method to assess anesthetic adequacy. This study used the BIS to predict the probability of recovery of consciousness after a single bolus induction dose of propofol or thiopental.

Methods

Twenty unpremedicated surgical patients were anesthetized with 4 mg/kg thiopental and 20 patients with 2 mg/kg propofol. The BIS was monitored throughout the study. After induction, before administration of neuromuscular blocking agent, a tourniquet was applied to one arm and inflated above the systolic blood pressure. This allowed preservation of the ability to move the hand after neuromuscular blocking agent onset. Patients were then prompted to squeeze the investigator's hand every 30 s, until they responded to the request. At the time of response, anesthesia was reinduced and the study terminated.

Results

The BIS at loss of consciousness and recovery of a response was not statistically different between propofol and thiopental. No patient with a BIS less than 58 was conscious. In both groups, a BIS of less than 65 signified a less than 5% probability of return of consciousness within 50 s.

Conclusion

The BIS can be used to predict probability of recovery of consciousness after a single injection of either thiopental or propofol.
Identification of Heterozygous and Homozygous Individuals with the Novel RYR1 Mutation Cys35Arg in a Large Kindred
Authors: Lynch P. J. , Krivosic-Horber R. , Reyford H. , Monnier N. , Quane K. , Adnet P. , Haudecoeur G. , Krivosic I. , McCarthy T. , Lunardi J.
Published: November 2003

Background

Malignant hyperthermia (MH) is a potentially fatal, often autosomal dominant, disorder of skeletal muscle and is triggered in susceptible people by all commonly used inhalational anesthetics. In this article, the authors describe a malignant hyperthermia susceptible (MHS) kindred in which both parents of the proband are MHS and are first-degree cousins. Haplotype analysis in this kindred with chromosome 19 linked markers revealed that the proband and another sibling were homozygous for the affected RYR1 allele.

Methods

Eighteen members of this large pedigree were investigated, with a clinical examination for signs of a myopathy, a caffeine halothane contracture test, a histo-enzymologic study on the muscle biopsies, and linkage analysis on genomic DNA isolated from family blood samples. RYR1 cDNA was amplified by polymerase chain reaction and was cloned and sequenced, facilitating mutation detection.

Results

Linkage analysis demonstrated linkage between RYR1-linked markers and MH susceptibility in this family. DNA sequencing identified a T to C transition at nucleotide position 103, resulting in the substitution of an arginine for cysteine 35, representing the most N-terminal mutation reported to date in the RYR1 gene. This mutation segregates fully with the MHS trait, generating a lod score of 4.65 in favor of linkage to MHS at a recombination frequency of 0.0.

Conclusions

The proband in this kindred is the first reported homozygote to have presented with an MH episode. The homozygotes in this pedigree do not have an overt myopathy. The sensitivity of muscle samples to caffeine clearly distinguished the two homozygotes from other heterozygous-susceptible individuals. No clear differentiation was observed with the halothane contracture results.
Negative and Selective Effects of Propofol on Isolated Swine Myocyte Contractile Function in Pacing-induced Congestive Heart Failure
Authors: Hebbar Latha , Dorman Hugh B. , Clair Mark J. , Roy Raymond C. , Spinale Francis G.
Published: November 2003

Background

Although propofol (2-6 di-isopropylphenol) is commonly used to induce and maintain anesthesia and sedation for surgery, systematic hypotension and reduced cardiac output can occur in patients with or without intrinsic cardiac disease. The effect of propofol on myocyte contractility after the development of congestive heart failure (CHF) remains unknown. This study tested the hypothesis that propofol would have direct effects on myocyte contractile function in both healthy and CHF cardiac myocyte preparations.

Methods

Isolated left ventricular (LV) myocyte contractile function (shortening velocity, micron/s) was examined in myocytes from five control pigs and in five pigs with pacing-induced CHF (240 beats/min, for 3 weeks) in the presence of propofol concentrations ranging from 1-6 micrograms/ml. In addition, myocyte contractility in response to beta-adrenergic receptor stimulation (isoproterenol, 10-50 nM) in the presence of propofol (3 micrograms/ml) was examined.

Results

Three weeks of pacing caused LV dysfunction consistent with CHF as evidenced by increased LV end-diastolic diameter (control 3.3 +/- 0.1 cm vs. CHF 5.6 +/- 0.2 cm; P < 0.05) and reduced LV fractional shortening (control 34 +/- 3% vs. CHF 12 +/- 2%, P < 0.05). Propofol (6 micrograms/ml) caused a concentration-dependent negative effect on velocity of shortening from baseline in both control (67 +/- 2 microns/s vs. 27 +/- 3 microns/s; P < 0.05) and CHF myocytes (29 +/- 1 microns/s vs. 15 +/- 1 microns/s; P < 0.05). Importantly, CHF myocytes were more sensitive than control myocytes to the negative effects of propofol on velocity of shortening at the lower concentration (1 microgram/ml). beta-adrenergic responsiveness was reduced by propofol (3 micrograms/ml) in control myocytes only.

Conclusions

Propofol has a direct and negative effect on basal myocyte contractile processes in the setting of CHF, which is more pronounced than that on healthy myocytes at reduced propofol concentrations.
Inaccuracies of Nitric Oxide Delivery Systems during Adult Mechanical Ventilation
Authors: Imanaka Hideaki , Hess Dean , Kirmse Max , Bigatello Luca M. , Kacmarek Robert M. , Steudel Wolfgang , Hurford William E.
Published: November 2003

Background

Various systems to administer inhaled nitric oxide (NO) have been used in patients and experimental animals. We used a lung model to evaluate five NO delivery systems during mechanical ventilation with various ventilatory patterns.

Methods

An adult mechanical ventilator was attached to a test lung configured to separate inspired and expired gases. Four injection systems were evaluated with NO injected either into the inspiratory circuit 90 cm proximal to the Y piece or directly at the Y piece and delivered either continuously or only during the inspiratory phase. Alternatively, NO was mixed with air using a blender and delivered to the high-pressure air inlet of the ventilator. Nitric oxide concentration was measured from the inspiratory limb of the ventilator circuit and the tracheal level using rapid- and slow-response chemiluminescence analyzers. The ventilator was set for constant-flow volume control ventilation, pressure control ventilation, pressure support ventilation, or synchronized intermittent mandatory ventilation. Tidal volumes of 0.5 l and 1 l were evaluated with inspiratory times of 1 s and 2 s.

Results

The system that premixed NO proximal to the ventilator was the only one that maintained constant NO delivery regardless of ventilatory pattern. The other systems delivered variable NO concentration during pressure control ventilation and spontaneous breathing modes. Systems that injected a continuous flow of NO delivered peak NO concentrations greater than the calculated dose. These variations were not apparent when a slow-response chemiluminescence analyzer was used.

Conclusions

NO delivery systems that inject NO at a constant rate, either continuously or during inspiration only, into the inspiratory limb of the ventilator circuit produce highly variable and unpredictable NO delivery when inspiratory flow is not constant. Such systems may deliver a very high NO concentration to the lungs, which is not accurately reflected by measurements performed with slow-response analyzers.
Treatment of Hypotension after Hyperbaric Tetracaine Spinal Anesthesia
Authors: Brooker Robert F. , Butterworth John F. IV , Kitzman Dalane W. , Berman Jeffrey M. , Kashtan Hillel I. , McKinley A. Colin
Published: November 2003

Background

Despite many advantages, spinal anesthesia often is followed by undesirable decreases in blood pressure, for which the ideal treatment remains controversial. Because spinal anesthesia-induced sympathectomy and management with a pure alpha-adrenergic agonist can separately lead to bradycardia, the authors hypothesized that epinephrine, a mixed alpha- and beta-adrenergic agonist, would more effectively restore arterial blood pressure and cardiac output after spinal anesthesia than phenylephrine, a pure alpha-adrenergic agonist.

Methods

Using a prospective, double-blind, randomized, cross-over study design, 13 patients received sequential infusions of epinephrine and phenylephrine to manage hypotension after hyperbaric tetracaine (10 mg) spinal anesthesia. Blood pressure, heart rate, and stroke volume (measured by Doppler echocardiography using the transmitral time-velocity integral) were recorded at baseline, 5 min after injection of tetracaine, and before and after management of hypotension with epinephrine and phenylephrine. Cardiac output was calculated by multiplying stroke volume x heart rate.

Results

Five min after placement of a hyperbaric tetracaine spinal anesthesia, significant decrease in systolic (from 143 +/- 6 mmHg to 125 +/- 5 mmHg; P < 0.001), diastolic (from 81 +/- 3 to 71 +/- 3; P < 0.001), and mean (from 102 +/- 4 to 89 +/- 3; P < 0.001) arterial pressures occurred. Heart rate (75 +/- 4 beats/min to 76 +/- 4 beat/min; P = 0.9), stroke volume (115 +/- 17 to 113 +/- 13; P = 0.9), and cardiac output (8.0 +/- 1 l/m to 8.0 +/- 1l/m; P = 0.8) did not change significantly after spinal anesthesia. Phenylephrine was effective at restoring systolic blood pressure after spinal anesthesia (120 +/- 6 mmHg to 144 +/- 5 mmHg; P < 0.001) but was associated with a decrease in heart rate from 80 +/- 5 beats/min to 60 +/- 4 beats/min (P < 0.001) and in cardiac output from 8.6 +/- 0.7 l/m to 6.2 +/- 0.7 l/m (P < 0.003). Epinephrine was effective at restoring systolic blood pressure after spinal anesthesia (119 +/- 5 mmHg to 139 +/- 6 mmHg; P < 0.001) and was associated with an increase in stroke volume from 114 +/- 12 ml to 142 +/- 17 (P < 0.001) and cardiac output from 7.8 +/- 0.6 l/m to 10.8 +/- 1.1 l/m (P < 0.001).

Conclusions

Epinephrine management of tetracaine spinal-induced hypotension increases heart rate and cardiac output and restores systolic arterial pressure but does not restore mean and diastolic blood pressure. Phenylephrine management of tetracaine spinal-induced hypotension decreases heart rate and cardiac output while restoring systolic, mean, and diastolic blood pressure.
Effects of a Dobutamine-induced Increase in Splanchnic Blood Flow on Hepatic Metabolic Activity in Patients with Septic Shock
Authors: Reinelt Helmut , Radermacher Peter , Fischer Gunther , Geisser Wolfgang , Wachter Ulrich , Wiedeck Heidemarie , Georgieff Michael , Vogt Josef
Published: November 2003

Background

Septic shock leads to increased splanchnic blood flow (Qspl) and oxygen consumption (VO2spl). The increased Qspl, however may not match the splanchnic oxygen demand, resulting in hepatic dysfunction. This concept of ongoing tissue hypoxia that can be relieved by increasing splanchnic oxygen delivery (DO2spl), however, was challenged because most of the elevated VO2spl was attributed to increased hepatic glucose production (HGP) resulting from increased substrate delivery. Therefore the authors tested the hypothesis that a dobutamine-induced increase in Qspl and DO2spl leads to increased VO2spl associated with accelerated HGP in patients with septic shock.

Methods

Twelve patients with hyperdynamic septic shock in whom blood pressure had been stabilized (mean arterial pressure > or = 70 mmHg) with volume resuscitation and norepinephrine received dobutamine to obtain a 20% increase in cardiac index (CI). Qspl, DO2spl, and VO2spl were assessed using the steady-state indocyanine green clearance technique with correction for hepatic dye extraction, and HGP was determined from the plasma appearance rate of stable, non-radio-active-labeled glucose using a primed-constant infusion approach.

Results

Although the increase in CI resulted in a similar increase in Qspl (from 0.91 +/- 0.21 to 1.21 +/- 0.34l.min-1.m2; P < 0.001) producing a parallel increase of DO2spl (from 141 +/- 33 to 182 +/- 44 ml.min-1.m2; P < 0.001), there was no effect on VO2spl (73 +/- 16 and 82 +/- 21 ml.min-1.m2, respectively). Hepatic glucose production decreased from 5.1 +/- 1.6 to 3.6 +/- 0.9 mg.kg-1.min-1 (P < 0.001).

Conclusions

In the patients with septic shock in whom blood pressure had been stabilized with volume resuscitation and norepinephrine, no delivery-dependency of VO2spl could be detected. Oxygen consumption was not related to the accelerated HGP either, and thus the concept that HGP dominates VO2spl must be questioned in well-resuscitated patients with septic shock.
Alpha4beta2 Neuronal Nicotinic Acetylcholine Receptors in the Central Nervous System Are Inhibited by Isoflurane and Propofol, but alpha7-type Nicotinic Acetylcholine Receptors Are Unaffected
Authors: Flood Pamela , Ramirez-Latorre Jose , Role Lorna
Published: November 2003

Background

The mechanisms of action of general anesthetics are not completely understood. Many general anesthetics are reported to potentiate gamma-aminobutyric acid (GABAA) and glycine receptors in the central nervous system (CNS) and to inhibit the muscle-type nicotinic acetylcholine receptor (nAChR). The effects of general anesthetics on another family of ligand-gated ion channel in the CNS, the nAChRs, have not been defined.

Methods

Two types of CNS acetylcholine receptor, the alpha 4 beta 2 receptor or the alpha 7 homomeric receptor, were expressed heterologously in Xenopus laevis oocytes. Using the standard two-microelectrode voltage-clamp technique, peak acetylcholinegated current was measured before and after coapplication of isoflurane or propofol.

Results

Coapplication of either isoflurane or propofol with acetylcholine resulted in potent, dose-dependent inhibition of the alpha 4 beta 2 receptor current with median inhibitory concentrations of 85 and 19 microM, respectively. The inhibition of the alpha 4 beta 2 receptor by both isoflurane and propofol appears to be competitive with respect to acetylcholine. The alpha 7 receptor current was not effected by either anesthetic.

Conclusions

The CNS-type nAChRs are differentially affected by isoflurane and propofol. The alpha 4 beta 2 receptor is affected by isoflurane more potently than the most sensitive GABAA or glycine receptor that has been reported, whereas the alpha 7 homomeric receptor is not affected by either anesthetic. Inhibition of specific subtypes of nAChRs in the CNS, along with potentiation of GABAA and glycine receptors, may contribute to the effects and side effects of general anesthetics.
Differential Sensitivities of Mammalian Neuronal and Muscle Nicotinic Acetylcholine Receptors to General Anesthetics
Authors: Violet J. M. , Downie D. L. , Nakisa R. C. , Lieb W. R. , Franks N. P.
Published: November 2003

Background

Nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of fast neurotransmitter-gated receptor channels that includes the gamma-aminobutyric acidA (GABAA), glycine and serotonin type 3 (5-HT3) receptors. Most previous work on the interactions of general anesthetics with nAChRs has involved the muscle-type receptor. The authors investigate the effects of general anesthetics on defined mammalian neuronal and muscle nAChRs expressed in Xenopus oocytes.

Methods

Complementary deoxyribonucleic acid (cDNA) or messenger ribonucleic acid (mRNA) encoding for various neuronal or muscle nAChR subunits was injected into Xenopus oocytes, and the resulting ACh-activated currents were studied using the two-electrode voltage-clamp technique. The effects of halothane, isoflurane, sevoflurane, and propofol on the peak acetylcholine-induced currents were investigated, and concentration-response curves were constructed.

Results

The neuronal nAChRs were found to be much more sensitive to general anesthetics than were the muscle nAChRs, with IC50 concentrations being 10- to 35-fold less for the neuronal receptors. For the inhalational general anesthetics, the IC50 concentrations were considerably less than the free aqueous concentrations that cause general anesthesia in mammals. In addition, qualitative (dependence on acetylcholine concentration) and quantitative (steepness of concentration-response curves) differences in the anesthetic interactions between the neuronal and muscle nAChRs suggest that different mechanisms of inhibition may be involved.

Conclusions

Although there is considerable uncertainty about the physiologic roles that neuronal nAChRs play in the central nervous system, their extraordinary sensitivity to general anesthetics, particularly the inhalational agents, suggests they may mediate some of the effects of general anesthetics at surgical, or even subanesthetic, concentrations.
Halothane and Enflurane Attenuate Pulmonary Vasodilation Mediated by Adenosine Triphosphate-sensitive Potassium Channels Compared to the Conscious State
Authors: Seki Sumihiko , Sato Kosei , Nakayama Masayasu , Murray Paul A.
Published: November 2003

Background

Adenosine triphosphate (ATP)-sensitive potassium (k+ATP) channels play an important role in pulmonary vasoregulation. However, the effects of volatile anesthetics on k+ATP channel-mediated pulmonary vasoregulation have not been elucidated. The purpose of the present study was to investigate the effects of halothane and enflurane anesthesia on the pulmonary vasodilator response to the selective k+ATP channel agonist lemakalim (BRJ38227) compared with that measured in the conscious state. The authors also investigated the extent to which endogenous neurohumoral vasoconstrictor mechanisms modulate the vasodilator response to k+ATP channel activation.

Method

Nineteen conditioned, male mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relationship. LPQ plots were generated by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during gradula (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. After preconstriction with the thromboxane analog, U46619 (9,11-dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha), the pulmonary vascular dose-response relationship for the k+ATP agonist lemakalim was assessed in the conscious and halothane-anesthetized states and also in the conscious and enflurane-anesthetized states. This protocol was repeated in conscious and halothane-anesthetized dogs after combined neurohumoral block with antagonists of sympathetic alpha 1 adrenoreceptors, arginine vasopressin V1-receptors, and angiotensin II receptors. The effect of the k+ATP antagonist glybenclamide on the baseline LPQ relationship and on the lemakalim dose-response relationship also was assessed in conscious dogs.

Results

Compared with the conscious state, halothane, enflurane and glybenclamide had no net effect on the baseline LPQ relationship. In contrast, halothane and enflurane attenuated (P < 0.05) the pulmonary vasodilator response to lemakalim compared with the conscious state. Glybenclamide also caused a rightward shift (P < 0.05) in the lemakalim dose-response relationship. Combined neurohumoral block did not modulate the vasodilator response to lemakalim in the conscious state. The halothane-induced attenuation of the vasodilator response to lemakalim was apparent after combined neurohumoral block.

Conclusion

These results indicate that halothane and enflurane act to reduce the magnitude of K+ATP channel-mediated pulmonary vasodilation. Reflex pulmonary vasoconstriction resulting from K+ATP mediated systematic hypotension does not alter the magnitude of the pulmonary vasodilator response to lemakalim nor is it responsible for the attenuated response to K+ATP channel activation during halothane anesthesia.
Sodium Channel in Human Malignant Hyperthermia
Authors: Fletcher Jeffrey E. , Wieland Steven J. , Karan Steven M. , Beech Jill , Rosenberg Henry
Published: November 2003

Background

The abundance of a specific sodium channel subunit (SkM2) appeared to be altered in vitro in cell cultures from persons susceptible to malignant hyperthermia. This study sought to determine whether these findings are artifacts of cell culture or whether they may be relevant to malignant hyperthermia.

Methods

Regulation of transcript levels of SkM2, a specific sodium channel alpha-subunit, was determined by mRNA analysis. Functional SkM2 protein was estimated in biopsy sections of vastus lateralis muscle by inhibiting the directly elicited muscle twitch by tetrodotoxin, which can differentiate at least three sodium currents in skeletal muscle.

Results

The transcript levels of SkM2 were depressed by 115-fold in six of seven persons susceptible to malignant hyperthermia; and the functional expression of the SkM2 protein, based on the tetrodotoxin sensitivity of the directly elicited twitch, was decreased by at least fourfold in muscle from persons susceptible to malignant hyperthermia compared with persons who were not susceptible.

Conclusions

As in previous studies in cell culture, altered mRNA and/or the functional expression of a specific subunit of the sodium channel (SkM2) was found in biopsy sections of muscle from all 12 persons examined who were susceptible to malignant hyperthermia but in none of the 16 nonsusceptible participants. Human malignant hyperthermia is a heterogeneous disorder, and the down-regulation of SkM2 may be involved in the final common pathway through which mutations in any one of several proteins, including the ryanodine receptor, could render a person susceptible.
Continuous Epidural Blockade Arrests the Postoperative Decrease in Muscle Protein Fractional Synthetic Rate in Surgical Patients
Authors: Carli Franco , Halliday Dave
Published: November 2003

Background

Epidural anesthesia with local anesthetics is associated with postoperative attenuation of nitrogen loss. The protein-sparing effect could be the result of either a decreased protein breakdown or increased protein synthesis. Although the role of epidural local anesthetics in effectively limiting the increase in postoperative protein breakdown is established at the whole-body level, it is necessary to determine whether the muscle protein fractional synthetic rate is directly modulated when nociceptive stimuli are blocked.

Methods

Twelve otherwise healthy patients scheduled for elective colorectal surgery, who were receiving a constant intake of nitrogen (0.1 kg-1.day-1) and calories (20 kcal.kg-1.day-1) before and after surgery, were randomly assigned to receive either general anesthesia (with thiopentone, vecuronium, fentanyl, or enflurane; control group, n = 6) or epidural anesthesia (T3-S5 sensory block with 0.75% bupivacaine) and general anesthesia (epidural group, n = 6). In the control group, postoperative analgesia was achieved with papaveretum given subcutaneously, whereas a continuous epidural bupivacaine infusion (T8-L5 sensory block) was maintained for 48 h in the epidural group. The postabsorptive muscle protein fractional synthetic rate was determined using a 6-h continuous infusion of 13C-labeled leucine (1 mg.kg-1.h-1), and the 13C enrichment in muscle biopsy specimens before surgery and 48 h after surgery was measured.

Results

Plateau 13C enrichment of plasma alpha-ketoisocaproate (taken to represent the intracellular leucine precursor pool enrichment for protein synthesis) was achieved during the 6-h infusion (mean coefficient of variation was 2.8%). Muscle protein synthesis at 48 h after operation compared with preoperative levels decreased significantly in the control group (P = 0.03). In contrast, it increased by 25% in the epidural group. Although this was not significantly (P = 0.15) different from preoperative levels, it was significantly greater than in the control patients.

Conclusions

Epidural infusion of local anesthetics begun before surgery and continued during the first 48 h after operation significantly attenuates the decrease in the postabsorptive muscle protein synthesis rate associated with surgical injury. Effective block of nociceptive stimuli thus preserves tissue protein synthesis.
Rehydration of Desiccated Baralyme Prevents Carbon Monoxide Formation from Desflurane in an Anesthesia Machine
Authors: Baxter Pamela J. , Kharasch Evan D.
Published: November 2003

Background

Desiccated carbon dioxide absorbents degrade desflurane, enflurane, and isoflurane to carbon monoxide (CO) in vitro and in anesthesia machines, which can result in significant clinical CO exposure. Carbon monoxide formation is highest from desflurane, and greater with Baralyme than with soda lime. Degradation is inversely related to absorbent water content, and thus the greatest CO concentrations occur with desflurane and fully desiccated Baralyme. This investigation tested the hypothesis that rehydrating desiccated absorbent can diminish CO formation.

Methods

Baralyme was dried to constant weight. Carbon monoxide formation from desflurane and desiccated Baralyme was determined in sealed 20.7-ml vials without adding water, after adding 10% of the normal water content (1.3% water), and after adding 100% of the normal water content (13% water) to the dry absorbent. Similar measurements were made using an anesthesia machine and circle system. Carbon monoxide was measured by gas chromatography-mass spectrometry.

Results

Carbon monoxide formation from desflurane in vitro was decreased from 10,700 ppm with desiccated Baralyme to 715 ppm and less than 100 ppm, respectively, when 1.3% and 13% water were added. Complete rehydration also decreased CO formation from enflurane and isoflurane to undetectable concentrations. Desflurane degradation in an anesthesia machine produced 2,500 ppm CO in the circuit, which was reduced to less than 180 ppm when the full complement of water (13%) was added to the dried absorbent.

Conclusions

Desflurane is degraded by desiccated Baralyme in an anesthesia machine, resulting in CO formation. Adding water to dried Baralyme is an effective means of reducing CO formation and the risk of intraoperative CO poisoning. Although demonstrated specifically for desflurane and Baralyme, rehydration is also applicable to enflurane and isoflurane, and to soda lime.
Isoflurane- and Halothane-mediated Dilation of Distal Bronchi in the Rat Depends on the Epithelium
Authors: Park Kyung W. , Dai Hai B. , Lowenstein Edward , Kocher Olivier N. , Sellke Frank W.
Published: November 2003

Background

Respiratory epithelium releases substance(s) that can modulate bronchoconstriction in response to constrictive agonists and enhance bronchodilation in response to certain bronchodilators. The hypothesis that the bronchodilatory effect of isoflurane and halothane depends on the epithelium was tested in rat distal bronchial segments.

Methods

Wistar rat bronchial segments of the fourth order (diameter approximately 100 microns) were dissected. After preconstriction with 5-hydroxytryptamine, each bronchial segment was exposed to increasing concentrations of 0% to 3% isoflurane or 0% to 3% halothane under four conditions: after epithelial rubbing, after pretreatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine, after pretreatment with the cyclooxygenase inhibitor indomethacin, or with no preintervention (control). Changes in bronchial diameter were monitored using an in vitro video detection system.

Results

Both isoflurane and halothane produced concentration-dependent bronchodilation (P < 0.001 for either anesthetic; 40% +/- 11% [mean +/- SD] dilation for 3% isoflurane and 57% +/- 10% dilation for 3% halothane). For both anesthetics, bronchodilation was significantly but incompletely attenuated by epithelial rubbing (12% +/- 7% dilation for 3% isoflurane [P < 0.01] and 31% +/- 10% dilation for 3% halothane [P < 0.01]), by pretreatment with indomethacin (20% +/- 8% dilation for 3% isoflurane [P < 0.02] and 21% +/- 9% dilation for 3% halothane [P < 0.001]), or by L-NNA (9% +/- 7% dilation for 3% isoflurane [P < 0.005] and 39% +/- 12% dilation for 3% halothane [P < 0.05]). Epithelial rubbing did not impair nitroprusside-associated bronchodilation.

Conclusions

Isoflurane- and halothane-mediated bronchodilation depends at least partially on the epithelium and may involve both a prostanoid and nitric oxide in distal rat bronchi.
Mild and Moderate Hypothermia Provide Better Protection than a Burst-suppression Dose of Thiopental against Ischemic Spinal Cord Injury in Rabbits
Authors: Matsumoto Mishiya , Iida Yasuhiko , Sakabe Takafumi , Sano Takanobu , Ishikawa Toshizo , Nakakimura Kazuhiko
Published: November 2003

Background

Controversy exists over the efficacy of different methods for protecting the spinal cord against experimental ischemic injury. Therefore, the authors compared the protective effects of thiopental with those of hypothermia (35 degrees C and 32 degrees C) on hindlimb motor functions and histopathology after transient spinal cord ischemia.

Methods

Twenty-seven New Zealand white rabbits were assigned to one of the four groups: a thiopental-normothermia group (burst-suppression dose of thiopental; esophageal temperature = 38 degrees C; n = 7), a halothane-mild hypothermia group (halothane, 1%; esophageal temperature = 35 degrees C; n = 7), a halothane-moderate hypothermia group (halothane, 1%; esophageal temperature = 32 degrees C; n = 6), and a halothane-normothermia group (halothane, 1%; esophageal temperature = 38 degrees C; n = 7). The animals were then subjected to 20 min of spinal cord ischemia produced by occlusion of the aorta distal to the origin of left renal artery. Hindlimb motor function was observed for 48 h after reperfusion. Histopathology of the lumbar spinal cord also was examined.

Results

All animals in the halothane-mild hypothermia and halothane-moderate hypothermia groups were neurologically normal 48 h after ischemia. There was no statistical difference in the final neurologic status and histopathology between the thiopental-normothermia and halothane-normothermia groups. However, the final neurologic status and histopathology in both groups were worse than in the halothane-mild hypothermia or halothane-moderate hypothermia groups. There was a strong correlation between the final neurologic status and the numbers of normal neurons in the anterior spinal cord.

Conclusions

These results suggest that mild and moderate hypothermia protects against ischemic spinal cord injury in rabbits, and a burst-suppression dose of thiopental does not offer any advantage over halothane.
Role of Adenosine in Isoflurane-induced Cardioprotection
Authors: Kersten Judy R. , Orth Karl G. , Pagel Paul S. , Mei David A. , Gross Garrett J. , Warltier David C.
Published: November 2003

Background

This investigation tested the hypothesis that adenosine (A1) receptor blockade modulates the cardioprotective effects of isoflurane.

Methods

Hemodynamics and percentage segment shortening (%SS) in the left anterior descending coronary artery (LAD) perfusion territory were evaluated in barbiturate-anesthetized dogs (n = 31) at selected intervals after pretreatment with the selective A1 receptor antagonist (8-cyclopentyl-1,3,dipropyl-xanthine; DPCPX 0.8 mg/kg, intravenously) or drug vehicle in the presence or absence of 1 minimum alveolar concentration (MAC) isoflurane. Dogs were subjected to five 5-min occlusions and reperfusions of the LAD, followed by 180 min of final reperfusion. Isoflurane was administered for 30 min before and during LAD occlusions and reperfusions and was discontinued at the onset of final reperfusion. Two other groups of dogs (n = 17) were used to measure interstitial concentrations of purines in the LAD region using a microdialysis technique in the presence and absence of isoflurane.

Results

Dogs receiving drug vehicle or DPCPX exhibited no recovery of %SS after 180 min of reperfusion (-5 +/- 7 and 5 +/- 11% of baseline, respectively, +/- SEM). In contrast, dogs receiving isoflurane alone demonstrated complete recovery of %SS at 60 min after reperfusion. DPCPX pretreatment partially attenuated isoflurane-induced enhancement of recovery of %SS (34 +/- 11% of baseline 180 min after reperfusion; P < 0.05). Interstitial purine concentrations were increased during multiple occlusions and reperfusions of the LAD in dogs not receiving isoflurane, but they were unchanged by coronary artery occlusion and reperfusion in dogs receiving isoflurane.

Conclusions

The results indicate that isoflurane-induced cardioprotection in stunned myocardium is partially mediated by adenosine type 1 receptor activation and is accompanied by decreases in endogenous adenosine release.
The Successful Implementation of Pharmaceutical Practice Guidelines
Authors: Lubarsky David A. , Glass Peter S. A. , Ginsberg Brian , de Dear Guy L. , Dentz Mark E. , Gan Tong J. , Sanderson Iain C. , Mythen Monty G. , Dufore Sherry , Pressley C. Christopher , Gilbert William C. , White William D. , Alexander M. Lynne , Coleman Robert L. , Rogers Mark , Reves J.G.
Published: November 2003

Background

Although approximately 2,000 medical practice guidelines have been proposed, few have been successfully implemented and sustained. We hypothesized that we could develop and institute practice guidelines to promote more appropriate use of costly anesthetics, to generate and sustain widespread compliance from a large physician group, and to decrease costs without adversely affecting clinical outcomes.

Methods

A prospective before and after comparison study was performed at a tertiary care medical center. Clinical outcomes data and times indicative of perioperative patient flow were collected on the first of two sets of patients 1 month before discussion of practice guidelines. Practice guidelines were developed by the physicians and their associated care team for the intraoperative use of anesthetic drugs. A drug distribution process was developed to aid compliance. Clinical outcomes data and times indicative of perioperative patient flow were collected on the second set of patients 1 month after institution of practice guidelines. Hospital drug costs and adherence to guidelines were noted throughout the study period and for each of the following 9 months by querying the database of an automated anesthesia record keeper.

Results

A total of 1,744 patients were studied. Drug costs decreased from 56 dollars per case to 32 dollars per case as a result of adherence to practice guidelines. Perioperative patient flow was minimally affected. Time (mean +/- SD) from end of surgery to arrival in the post-anesthesia care unit (PACU) increased from 11 +/- 7 min before the authors instituted practice guidelines to 14 +/- 8 min after practice guidelines (P < 0.0001). Admission of inpatients to the PACU receiving monitored anesthesia care increased from 6.5 to 12.9% (P < 0.02). Perioperative patient flow and clinical outcomes were not otherwise adversely affected. Compliance and cost savings have been sustained.

Conclusions

This study is an example of a successful physician-directed program to promote more appropriate utilization of health care resources. Cost savings were obtained without any substantial changes in clinical outcomes. Institution of similar practice guidelines should result in pharmaceutical savings in the range of 50% at tertiary care centers around the country, with a slightly smaller degree of savings expected at institutions with more ambulatory surgery.
Effects of Low-flow Sevoflurane Anesthesia on Renal Function
Authors: Bito Hiromichi , Ikeuchi Yukako , Ikeda Kazuyuki
Published: November 2003

Background

The safety of low-flow sevoflurane anesthesia, during which CF2=C(CF3)-O-CH2F (compound A) is formed by sevoflurane degradation, in humans has been questioned because compound A is nephrotoxic in rats. Several reports have evaluated renal function after closed-circuit or low-flow sevoflurane anesthesia, using blood urea nitrogen (BUN) and serum creatinine as markers. However, these are not the more sensitive tests for detecting renal damage. This study assessed the effects of low-flow sevoflurane anesthesia on renal function using not only BUN and serum creatinine but also creatinine clearance and urinary excretion of kidney-specific enzymes, and it compared these values with those obtained in high-flow sevoflurane anesthesia and low-flow isoflurane anesthesia.

Methods

Forty-eight patients with gastric cancer undergoing gastrectomy were studied. Patients were randomized to receive sevoflurane anesthesia with fresh gas flow of 1 l/min (low-flow sevoflurane group; n = 16) or 6-10 l/min (high-flow sevoflurane group; n = 16) or isoflurane anesthesia with a fresh gas flow of 1 l/min (low-flow isoflurane group; n = 16). In all groups, the carrier gas was oxygen/nitrous oxide in the ratio adjusted to ensure a fractional concentration of oxygen in inspired gas (FiO2) of more than 0.3. Fresh Baralyme was used in the low-flow sevoflurane and low-flow isoflurane groups. Glass balls were used instead in the high-flow sevoflurane group, with the fresh gas flow rate adjusted to eliminate rebreathing. The compound A concentration was measured by gas chromatography. Gas samples taken from the inspiratory limb of the circle system at 1-h intervals were analyzed. Blood samples were obtained before and on days 1, 2, and 3 after anesthesia to measure BUN and serum creatinine. Twenty-four-hour urine samples were collected before anesthesia and for each 24-h period from 0 to 72 h after anesthesia to measure creatinine, N-acetyl-beta-D-glucosaminidase, and alanine aminopeptidase.

Results

The average inspired concentration of compound A was 20 +/- 7.8 ppm (mean +/- SD), and the average duration of exposure to this concentration was 6.11 +/- 1.77 h in the low-flow sevoflurane group. Postanesthesia BUN and serum creatinine concentrations decreased, creatinine clearance increased, and urinary N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase excretion increased in all groups compared with preanesthesia values, but there were no significant differences between the low-flow sevoflurane, high-flow sevoflurane, and low-flow isoflurane groups for any renal function parameter at any time after anesthesia.

Conclusions

The only difference between the low-flow and high-flow sevoflurane groups was compound A formation, and postanesthesia laboratory data showed no significant effects of compound A formation during sevoflurane anesthesia on renal function. No significant effects on renal function were observed in either the low-flow or high-flow sevoflurane groups compared with the low-flow isoflurane group.
Hypoxic Pulmonary Vasoconstriction in Nonventilated Lung Areas Contributes to Differences in Hemodynamic and Gas Exchange Responses to Inhalation of Nitric Oxide
Authors: Benzing Albert , Mols Georg , Brieschal Thomas , Geiger Klaus
Published: November 2003

Background

Enhancement of hypoxic pulmonary vasoconstriction (HPV) in nonventilated lung areas by almitrine increases the respiratory response to inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). Therefore the authors hypothesized that inhibition of HPV in nonventilated lung areas decreases the respiratory effects of NO.

Methods

Eleven patients with severe ARDS treated by venovenous extracorporeal lung assist were studied. Patients' lungs were ventilated at a fraction of inspired oxygen (F[I(O2)]) of 1.0. By varying extracorporeal blood flow, mixed venous oxygen tension (P[O2]; partial oxygen pressure in mixed venous blood [PV(O2)]) was adjusted randomly to four levels (means, 47, 54, 64 and 84 mmHg). Extracorporeal gas flow was adjusted to prevent changes in mixed venous carbon dioxide tension [PV(CO2)]). Hemodynamic and gas exchange variables were measured at each level before, during, and after 15 ppm NO.

Results

Increasing PV(O2) from 47 to 84 mmHg resulted in a progressive decrease in lung perfusion pressure (PAP-PAWP; P < 0.05) and pulmnonary vascular resistance index (PVRI; P < 0.05) and in an increase in intrapulmonary shunt (Q[S]/Q[T]; P < 0.05). PV(CO2) and cardiac index did not change. Whereas the NO-induced reduction in PAP-PAWP was smaller at high PV(O2), NO-induced decrease in Q(S)/Q(T) was independent of baseline PV(O2). In response to NO, arterial P(O2) increased more and arterial oxygen saturation increased less at high compared with low PV(O2).

Conclusion

In patients with ARDS, HPV in nonventilated lung areas modifies the hemodynamic and respiratory response to NO. The stronger the HPV in nonventilated lung areas the more pronounced is the NO-induced decrease in PAP-PAWP. In contrast, the NO-induced decrease in Q(S)/Q(T) is independent of PV(O2) over a wide range of PV(O2) levels. The effect of NO on the arterial oxygen tension varies with the level of PV(O2) by virtue of its location on the oxygen dissociation curve.
Xenon Provides Faster Emergence from Anesthesia than Does Nitrous Oxide-sevoflurane or Nitrous Oxide-isoflurane
Authors: Goto Takahisa , Saito Hayato , Shinkai Masahiro , Nakata Yoshinori , Ichinose Fumito , Morita Shigeho
Published: November 2003

Background

Xenon, an inert gas with anesthetic properties (minimum alveolar concentration [MAC] = 71%), has an extremely low blood:gas partition coefficient (0.14). Therefore, we predicted that xenon would provide more rapid emergence from anesthesia than does N2O+isoflurane or N2O+sevoflurane of equivalent MAC.

Methods

Thirty American Society of Anesthsiologists class I or II patients undergoing total abdominal hysterectomy were randomly assigned to receive 60% xenon, 60% N2O + 0.5% isoflurane, or 60% N2O + 0.70% sevoflurane (all concentrations are end-tidal: n = 10 per group). After placement of an epidural catheter, anesthesia was induced with standardized doses of midazolam, thiopental, and fentanyl. Thirty minutes later, xenon, N2O+isoflurane, or N2O+sevoflurane was started as previously assigned. These regimens were supplemented with epidural anesthesia with mepivacaine so that the mean arterial pressure and heart rate were controlled within 20% of the preoperative values. At the end of operation lasting approximately 2 h, all inhalational anesthetics were discontinued, and the patients were allowed to awaken while breathing spontaneously on an 8 l/min inflow of oxygen. A blinded investigator recorded the time until the patient opened her eyes on command (T1), was judged ready for extubation (T2), could correctly state her name, her date of birth, and the name of the hospital (T3), and could count backward from 10 to 1 in less than 15 s (T4).

Results

Emergence times from xenon anesthesia were: T1, 3.4 +/- 0.9 min; T2, 3.6 +/- 1 min; T3, 5.2 +/- 1.4 min; and T4, 6.0 +/- 1.6 min (mean +/- SD). These were one half to one third of those from N2O+sevoflurane (T1, 6.0 +/- 1.7 min; T4, 10.5 +/- 2.5 min) or N2O+isoflurane (T1, 7.0 +/- 1.9 min; T4, 14.3 +/- 2.8 min) anesthesia. The three groups did not differ in terms of patient demographics, the duration of anesthesia, the amount of epidural mepivacaine administered, or the postoperative pain rating. No patient could recalls intraoperative events.

Conclusions

Emergence from xenon anesthesia is two or three times faster than that from equal-MAC N2O+isoflurane or N2O+sevoflurane anesthesia.