bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Motion on the Performance of Pulse Oximeters in Volunteers (Revised publication)
Authors: Barker Steven J. , Shah Nitin K.
Published: November 2003

Background

Pulse oximetry is considered a standard of care in both the operating room and the postanesthetic care unit, and it is widely used in all critical care settings. Pulse oximeters may fail to provide valid SpO2 data in various situations that produce low signal-to-noise ratio. Motion artifact is a common cause of oximeter failure and loss of accuracy. This study compares the accuracy and data dropout rates of three current pulse oximeters during standardized motion in healthy volunteers.

Methods

Ten healthy volunteers were monitored by three different pulse oximeters: Nellcor N-200, Nellcor N-3000, and Masimo SET (prototype). Sensors were placed on digits 2, 3, and 4 of the test hand, which was strapped to a mechanical motion table. The opposite hand was used as a stationary control and was monitored with the same pulse oximeters and an arterial cannula. Arterial oxygen saturation was varied from 100% to 75% by changing the inspired oxygen concentration. While SpO2 was both constant and changing, the oximeter sensors were connected before and during motion. Oximeter errors and dropout rates were digitally recorded continuously during each experiment.

Results

If the oximeter was functioning before motion began, the following are the percentages of time when the instrument displayed an SpO2 value within 7% of control: N-200 = 76%, N-3000 = 87%, and Masimo = 99%. When the oximeter sensor was connected after the beginning of motion, the values were N-200 = 68%, N-3000 = 47%, and Masimo = 97%. If the alarm threshold was chosen SpO2 less than 90%, then the positive predictive values (true alarms/total alarms) are N-200 = 73%, N-3000 = 81%, and Masimo = 100%. In general, N-200 had the greatest SpO2 errors and N-3000 had the highest dropout rates.

Conclusions

The mechanical motions used in this study significantly affected oximeter function, particularly when the sensors were connected during motion, which requires signal acquisition during motion. The error and dropout rate performance of the Masimo was superior to that of the other two instruments during all test conditions. Masimo uses a new paradigm for oximeter signal processing, which appears to represent a significant advance in low signal-to-noise performance.
Isoflurane Attenuates Early Neutrophil-independent Hypoxia-Reoxygenation Injuries in the Reperfused Liver in Fasted Rats
Authors: Kon Shinpei , Imai Mie , Inaba Hideo
Published: November 2003

Background

Ischemia-hypoxia followed by reperfusion and reoxygenation injures cells and organs. Previous studies have indicated that isoflurane may protect organs from ischemia-reperfusion or hypoxia-reoxygenation. This study investigated the ability of isoflurane to protect the liver from hypoxia-reoxygenation injury and the mechanisms of this phenomenon.

Methods

The isolated liver was perfused at a constant pressure of 12 cm H2O with a modified Krebs-Ringer-bicarbonate solution saturated with a 95% oxygen/5% carbon dioxide gas mixture. Hypoxic perfusion produced by decreasing the oxygen concentration in the gas mixture to 10% was followed by perfusion at 95% oxygen for 60 min. Viability of the liver was assessed by lactate dehydrogenase release from the liver. Isoflurane at 0.5, 1, and 2 minimum alveolar concentration was administered to assess the effect of isoflurane on hypoxia-reperfusion injury. To determine the effect of isoflurane on extracellular generation of superoxide in the liver, the reduction of ferricytochrome c with or without superoxide dismutase was measured.

Results

Lactate dehydrogenase release was transiently but dramatically increased by reoxygenation and significantly attenuated by 1 and 2 minimum alveolar concentration of isoflurane. Suppression of Kupffer cells with gadolinium chloride also attenuated the lactate dehydrogenase release. Isoflurane significantly reduced the superoxide generation on reperfusion.

Conclusions

The results show that isoflurane protected the liver from an early reoxygenation injury presumably mediated by Kupffer cells. The mechanisms of the inhibitory effects of isoflurane on the injury may involve suppression of extracellular superoxide generation during reoxygenation.
Initial Contractile Response of Isolated Rat Heart Cells to Halothane, Enflurane, and Isoflurane
Authors: Wheeler David M. , Rice Todd R. , duBell William H. , Spurgeon Harold A.
Published: November 2003

Background

In several beating cardiac muscle preparations, a short-lived increase in twitch tension or amplitude has been observed when they were exposed abruptly to solutions containing halothane or enflurane. As exposure to the anesthetics was continued, the expected negative inotropic effect became evident after the short-lived increase in twitch. No such increase in twitch has been reported during exposure to isoflurane. It has been hypothesized that this short-lived increase in twitch is caused by an enhancement of calcium release from the sarcoplasmic reticulum, but other mechanisms have not been excluded.

Methods

Freshly isolated, single rat ventricular cells were stimulated to beat at room temperature and abruptly exposed to solutions containing halothane (0.25-0.64 mM), enflurane (0.69-1 mM), or isoflurane (0.31-0.54 mM). During these exposures, twitch amplitude was measured and intracellular calcium concentration was followed using the calcium-sensitive dye indo-1. In some experiments, the whole-cell patch-clamp technique was used to measure membrane current. In addition, in several cells the sarcoplasmic reticulum calcium content was assessed through the response to brief pulses of caffeine.

Results

Both the twitch amplitude and the intracellular calcium transient were increased temporarily in cells abruptly exposed to halothane or enflurane. No such behavior was found with isoflurane. After continued exposure to all three agents, both the twitch amplitude and the calcium transient were less than control. During the beats exhibiting an increase in twitch, no alteration in the relation between cell length (twitch amplitude) and the intracellular calcium transient was found compared with control conditions. In addition, the temporary increase in twitch amplitude occurred in cells contracting under voltage-clamp control when halothane was introduced, and it was not associated with any increase in the calcium current. The sarcoplasmic reticulum calcium content at the time of the halothane-induced increase in twitch also was not increased.

Conclusions

The short-lived increase in twitch after abrupt exposure to halothane or enflurane is related to increased intracellular calcium during the beat and not to any changes in myofilament sensitivity to calcium. Because these results eliminate most alternative explanations for this phenomenon, the authors conclude that halothane, and probably also enflurane, increases the fraction of calcium released from the sarcoplasmic reticulum with each heart beat. Isoflurane appears to lack this action.
Halothane, Isoflurane, and Sevoflurane Reduce Postischemic Adhesion of Neutrophils in the Coronary System
Authors: Kowalski Christian , Zahler Stefan , Becker Bernhard F. , Flaucher Andreas , Conzen Peter F. , Gerlach Eckehart , Peter Klaus
Published: November 2003

Background

Polymorphonuclear neutrophils (PMNs) contribute to postischemic reperfusion damage in many organs and tissues, a prerequisite being adhesion of PMNs to vascular endothelial cells. Because adhesion processes involve orderly interactions of membrane proteins, it appeared possible that "membrane effects" of volatile anesthetics could interfere. We investigated the effects of halothane, isoflurane, and sevoflurane on postischemic adhesion of human PMNs in the intact coronary system of isolated perfused guinea pig hearts.

Methods

The hearts (n = 7-10 per group) were perfused in the "Langendorff" mode under conditions of constant flow (5 ml/min) using modified Krebs-Henseleit buffer equilibrated with 94.4% oxygen and 5.6% carbon dioxide. Global myocardial ischemia was induced by interrupting perfusion for 15 min. In the second minute of reperfusion (5 ml/min), a bolus dose of 6 x 10(5) PMNs was injected into the coronary system. The number of cells reemerging in the coronary effluent was expressed as a percentage of the total number of applied PMNs. Halothane, isoflurane, and sevoflurane, each at 1 and 2 minimal alveolar concentration (MAC), were vaporized in the gas mixture and applied from 14 min before ischemia until the end of the experiment.

Results

Under nonischemic conditions, 24.7 +/- 1.3% of the injected neutrophils did not reemerge from the perfused coronary system. Subjecting the hearts to global ischemia augmented retention (36.4 +/- 2.8%, P < .05). Application of halothane reduced adhesion of neutrophils to 22.6 +/- 2.1% and 24.2 +/- 1.8% at 1 and 2 MAC, respectively (P < .05). Exposure to 1 and 2 MAC isoflurane was similarly effective, whereas basal adhesion was not significantly influenced. Sevoflurane-treated hearts (1 and 2 MAC) also showed decreased adhesion of PMNs (23 +/- 2.3% and 24.8 +/- 1.8%, respectively; P < .05) and an identical reduction resulted when sevoflurane (1 MAC) was applied only with the onset of reperfusion.

Conclusions

Although the mechanism of action of volatile anesthetics remains unclear in these preliminary studies, their inhibitory effect on ischemia-induced adhesion of PMNs may be beneficial for the heart during general anesthesia.
In Vitro Effects of Dantrolene on Rat Myocardium
Authors: Fratea Sylvia , Langeron Olivier , Lecarpentier Yves , Coriat Pierre , Riou Bruno
Published: November 2003

Background

Dantrolene is the only known effective treatment for malignant hyperthermia. However, its effects on myocardial contraction and relaxation remain debatable.

Methods

The effects of dantrolene (10(-5)-10(-3) M) on the contractility of rat left ventricular papillary muscles were investigated in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, 2.5 and 0.5 mM Ca2+, stimulation frequency 12 pulses/min). The authors studied contraction, relaxation, contraction-relaxation coupling under high and low load, energetics, and postrest potentiation. The effects of dantrolene after depletion of catecholamine stores with reserpine also were studied.

Results

Dantrolene induced a moderate concentration-dependent negative inotropic effect at a low calcium concentration (active force at 10(-4) M: 86 +/- 14% of control values, P < 0.05), but not at a high calcium concentration. Dantrolene did not significantly modify the curvature of the force-velocity relation, suggesting that it did not modify myocardial energetics. Dantrolene induced no significant lusitropic effect under low load, suggesting that it did not modify calcium uptake by the sarcoplasmic reticulum. Dantrolene did not significantly modify postrest potentiation and postrest potentiation recovery, suggesting that it did not modify maximum capacity of calcium release by the sarcoplasmic reticulum nor its postrest resetting capacity. Reserpine did not modify the myocardial effects of dantrolene.

Conclusions

In rat myocardium, dantrolene did not modify any of the sarcoplasmic reticulum functions tested (uptake, release, postrest recovery). Dantrolene induced a moderate negative inotropic effect, probably mediated by a decrease in transarcolemmal calcium entry, and this negative inotropic effect was blunted by an increase in calcium concentration.
Neural Blockade for Diagnosis and Prognosis
Authors: Hogan Quinn H. , Abram Stephen E.
Published: November 2003

On the basis of the published material reviewed above, we conclude that there are many limitations that weaken the theoretic basis for neural blockade as a diagnostic or prognostic tool. In addition, these procedures in general lack thorough documentation of clinical usefulness. Reasonable employment of diagnostic neural blockade, therefore, requires not only care in technique and confirmation of effects, but also caution in interpretation and application of the results. This critical evaluation needs to be tempered, however, by two further observations. Experienced and observant clinicians have found these procedures may, on certain occasions, provide information that is helpful in guiding subsequent therapy, so we should not be in haste to dismiss the accumulated judgment of practitioners. Finally, the confusion and complexity that typifies diagnosis in chronic pain may justify the selective use of diagnostic blocks that make anatomic and physiologic sense, even if their validity is incompletely proved.
Hypoxic Pulmonary Vasoconstriction in Human Lungs
Authors: Hambraeus-Jonzon Kristina , Bindslev Lars , Mellgard Ase Jolin , Hedenstierna Goran
Published: November 2003

Background

A stimulus-response relation between alveolar oxygen tension and pulmonary vascular resistance has been observed in animals. This study investigated this relation in healthy human lungs. The distribution of pulmonary blood flow was measured during unilateral (1) graded hypoxia (fractional concentration of oxygen in inspired gas [FIO2] = 0.12, 0.08, and 0.05) and contralateral hyperoxia (FIO2 = 1.0; n = 6); (2) single-step hypoxia (FIO2 = 0.05) and contralateral hyperoxia (n = 5); and (3) normobaric hyperoxia and contralateral normoxia (FIO2 = 0.25; n = 6).

Methods

Seventeen patients with healthy lungs were studied during intravenous anesthesia. The lungs were separately and synchronously ventilated. The relative perfusion of each lung was assessed by the inert gas (sulfurhexafluoride) elimination technique.

Results

(1) Unilateral graded hypoxia reduced the perfusion of the hypoxic lung from a mean (+/-SD) of 52 (2)% of cardiac output (Q) during bilateral hyperoxia, to 47 (5)% (P > 0.05) 40 (3)% (P < 0.01), and 30 (8)% (P < 0.001) of Q, respectively. These progressive reductions in the perfusion of the hypoxic lung were all significantly different from each other. (2) Unilateral single-step hypoxia caused a blood flow diversion of the same magnitude as when the lung was previously ventilated with FiO2 of 0.12 and 0.08. The perfusion of the hypoxic lung was reduced from 46 (9)% of Q (bilateral hyperoxia) to 26 (4)% of Q (P < 0.01). (3) Unilateral hyperoxia did not significantly change the relative blood flow distribution between the two lungs or the pulmonary artery pressure.

Conclusions

A stimulus-response relation between graded hypoxia and blood flow diversion defines hypoxic pulmonary vasoconstriction in the normal human lung. Hyperoxia has no significant effect on vascular resistance in the normal human lung.
Predicting Difficult Intubation with Indirect Laryngoscopy
Authors: Yamamoto Ken , Tsubokawa Tsunehisa , Shibata Keizo , Ohmura Shigeo , Nitta Shunichi , Kobayashi Tsutomu
Published: November 2003

Background

It is not always possible to predict when tracheal intubation will be difficult or impossible. The authors wanted to determine whether indirect laryngoscopy could identify patients in whom intubation was difficult.

Methods

Indirect laryngoscopy was done in 2,504 patients. The Wilson risk sum score and the modified Mallampati score were also studied in a different series of 3,680 patients for comparison. These predictive methods were compared according to three parameters: positive predictive value, sensitivity, and specificity.

Results

Of 6,184 patients studied, the trachea proved difficult to intubate in 82 (1.3%). Positive predictive value (31%) and specificity (98.4%) with indirect laryngoscopy were greater than the other two predictive methods (P < 0.01), whereas sensitivity with indirect laryngoscopy (69.2%) was greater than that of the Wilson risk sum score (55.4%) (P < 0.01).

Conclusions

Although in 15% of patients indirect laryngoscopy could not be performed because of excessive gag reflex, indirect laryngoscopy can serve as an effective method to predict difficult intubation.
Dexmedetomidine as an Anesthetic Adjunct in Coronary Artery Bypass Grafting
Authors: Jaionen Jouko , Hynynen Markku , Kuitunen Anne , Heikkila Hannu , Perttila Juha , Salmenpera Markku , Valtonen Mika , Aantaa Riku , Kallio Antero
Published: November 2003

Background

Alpha 2-adrenergic agonists decrease sympathetic tone with ensuing attenuation of neuroendocrine and hemodynamic responses to anesthesia and surgery. The effects of dexmedetomidine, a highly specific alpha 2-adrenergic agonist, on these responses have not been reported in patients undergoing coronary artery bypass grafting.

Methods

Eighty patients scheduled for elective coronary artery bypass grafting received, in a double-blind manner, either a saline placebo or a dexmedetomidine infusion, initially 50 ng.kg-1.min-1 for 30 min before induction of anesthesia with fentanyl, and then 7 ng.kg-1.min-1 unit the end of surgery. Filling pressures, blood pressure, and heart rate were controlled by intravenous fluid and by supplemental anesthetics and vasoactive drugs.

Results

Compared with placebo, dexmedetomidine decreased plasma norepinephrine concentrations by 90%, attenuated the increase of blood pressure during anesthesia (3 vs. 24 mmHg) and surgery (2 vs. 14 mmHg), but increased slightly the need for intravenous fluid challenge (29 vs. 20 patients) and induced more hypotension during cardiopulmonary bypass (9 vs. 0 patients). Dexmedetomidine decreased the incidence of intraoperative (2 vs. 13 patients) and postoperative (5 vs. 16 patients) tachycardia. Dexmedetomidine also decreased the need for additional doses of fentanyl (3.1 vs. 5.4), the increments of enflurane (4.4 vs. 5.6), the need for beta blockers (3 vs. 11 patients), and the incidence of fentanyl-induced muscle rigidity (15 vs. 33 patients) and postoperative shivering (13 vs. 23 patients).

Conclusions

Intraoperative intravenous infusion of dexmedetomidine to patients undergoing coronary artery revascularization decreased intraoperative sympathetic tone and attenuated hyperdynamic responses to anesthesia and surgery but increased the propensity toward hypotension.
Neutrophil Adhesion Molecule Expression Is Comparable in Perinatal Rabbits and Humans
Authors: Ramamoorthy Chandra , Kovarik Daniel W. , Winn Robert K. , Harlan John M. , Sharar Sam R.
Published: November 2003

Background

Human newborns, particularly those born before full term, are more susceptible to bacterial infections as a result of impaired host defense mechanisms. Compared with adults, circulating leukocytes from human newborns (preterm and full-term gestations) and newborn rabbits (full-term gestation) have low resting levels of CD62L (L-selectin) and do not significantly increase surface expression of CD18 after inflammatory stimulation. To determine the potential utility of preterm rabbits in investigations of perinatal human conditions, the authors compared the surface expression of the beta 2-integrin CD18 and CD62L (L-selectin) on polymorphonuclear leukocytes (PMNs) from perinatal rabbits and perinatal humans, both under resting conditions and after in vitro activation with inflammatory stimulants.

Methods

After erythrocyte lysis of whole-blood samples, leukocytes from 7-day-old, full-term (31-day gestation), and preterm (24-day gestation) rabbits, as well as full-term (37-42 week gestation) and preterm (27-36 week gestation) human newborns were prepared and stimulated in vitro at 37 degrees C with either C5a or phorbol myristate acetate. After fluorescence labeling of CD18 and CD62L with monoclonal antibodies, PMN adhesion molecule expression was assessed by flow cytometry.

Results

Constitutive CD18 expression was not significantly different between perinatal and adult humans but was reduced in all perinatal rabbits compared with adults. Inflammatory stimulation caused significant increases in CD18 expression in adult human PMNs but not in full-term and preterm newborns. Changes in CD18 expression in adult and preterm rabbits after stimulation, although in the same direction as humans, were more variable. In both species, constitutive CD62L expression on PMNs from all perinates was significantly lower than in adults. However, CD62L was shed to similar degrees after inflammatory stimulation in all groups.

Conclusions

Preterm rabbits may provide a potentially useful experimental model to study PMN adhesion and host defense in the perinatal period, particularly preterm gestations. Specific advantages and limitations of rabbits in such studies are discussed.
Effects of Propofol on Sodium Channel-dependent Sodium Influx and Glutamate Release in Rat Cerebrocortical Synaptosomes
Authors: Ratnakumari L. , Hemmings H. C.
Published: November 2003

Background

Previous electrophysiologic studies have implicated voltage-dependent Na+ channels as a molecular site of action for propofol. This study considered the effects of propofol on Na+ channel-mediated Na+ influx and neurotransmitter release in rat brain synaptosomes (isolated presynaptic nerve terminals).

Methods

Purified cerebrocortical synaptosomes from adult rats were used to determine the effects of propofol on Na+ influx through voltage-dependent Na+ channels (measured using 22Na+) and intracellular [Na+] (measured by ion-specific spectrofluorimetry). For comparison, the effects of propofol on synaptosomal glutamate release evoked by 4-aminopyridine (Na+ channel dependent), veratridine (Na+ channel dependent), KCi (Na+ channel independent) were studied using enzyme-coupled fluorimetry.

Results

Propofol inhibited veratridine-evoked 22Na+ influx (inhibitory concentration of 50% [IC50] = 46 microM; 8.9 microM free) and changes in intracellular [Na+] (IC50 = 13 microM; 6.3 microM free) in synaptosomes in a dose-dependent manner. Propofol also inhibited 4-aminopyridine-evoked (IC50 = 39 microM; 19 microM free) and veratridine (20 microM)-evoked (IC50 = 30 microM; 14 microM free), but not KCi-evoked (up to 100 microM) glutamate release from synaptosomes.

Conclusions

Inhibition of Na+ channel-mediated Na+ influx, increased in intracellular [Na+], and glutamate release occurred in synaptosomes at concentrations of propofol achieved clinically. These results support a role for neuronal voltage-dependent Na+ channels as a molecular target for presynaptic general anesthetic effects.
Halothane Interactions with Nicotinic Acetylcholine Receptor Membranes
Authors: Raines Douglas E. , McClure Katie B.
Published: November 2003

Background

Although it has been suggested that anesthetics alter protein conformational states by binding to nonpolar sites within the interior regions of proteins, the rate and extent to which anesthetics penetrate membrane proteins has not been characterized. The authors report the use of steady-state and stopped-flow spectroscopy to characterize the interactions of halothane with receptor membranes.

Methods

Steady-state and stopped-flow fluorescence spectroscopy was used to characterize halothane quenching of nicotinic acetylcholine receptor (nAcChoR)-rich membrane intrinsic fluorescence and the rate of isoflurane-induced nAcChoR desensitization.

Results

At equilibrium, halothane quenched only 54 +/- 1.4% of all tryptophan fluorescence. Diethyl ether failed to reduce fluorescence quenching by halothane, suggesting that it does not bind to the same protein sites as halothane. Stopped-flow fluorescence traces defined two kinetic components of quenching: a fast component that occurred in less than 1 ms followed by a slower biphasic fluorescence decay. Protein unfolding with sodium dodecyl sulfate reduced halothane's Stern-Volmer quenching constant, eliminated the biphasic decay, and rendered fluorescence accessible to quenching by halothane within 1 ms. Functional studies indicate that anesthetic-induced desensitization of nAcChoR occurs in less than 2 ms.

Conclusions

Unquenchable fluorescence arises from tryptophan residues that are buried within the protein and protected from halothane. Sodium dodecyl sulfate unfolds membrane proteins and allows previously buried fluorescence protein residues to be rapidly and homogeneously quenched by halothane. Halothane quenches protein components of nAcChoR membranes over the same concentration range and time scale that it exerts its functional effects, a finding that is generally consistent with a protein site of action.
Addition of Epinephrine to Intrathecal Bupivacaine and Sufentanil for Ambulatory Labor Analgesia
Authors: Campbell David C. , Banner Robert , Crone Lesley-Ann , Gore-Hickman Wendy , Yip Ray W.
Published: November 2003

Background

The intrathecal combination of sufentanil and bupivacaine provides rapid, effective analgesia for labor with a limited duration. Many anesthesiologists have concerns that the use of intrathecal local anesthetics precludes maternal ambulation. This prospective, randomized, double-blind study was designed to determine whether the addition of epinephrine to the combination of sufentanil and bupivacaine would prolong intrathecal analgesia for labor. Patients' ability to ambulate was also assessed.

Methods

Thirty-nine patients received either an intrathecal control dose of 10 micrograms sufentanil plus 2.5 mg bupivacaine plus 0.2 ml normal saline (control group); or 10 micrograms sufentanil plus 2.5 mg bupivacaine plus 0.2 ml (0.2 mg) of epinephrine (EPI group).

Results

Seven patients (3 control, 4 EPI) delivered vaginally and two (1 control, 1 EPI) required cesarean delivery before requesting epidural analgesia. The duration (mean +/- SD) of intrathecal labor analgesia was prolonged significantly by the addition of epinephrine: control (n = 15): 145 +/- 23 min; EPI (n = 15): 188 +/- 25 min (P < 0.0001). Maternal ambulation was demonstrated in 100% (19 of 19) of the control group and in 80% (16 of 20) of the EPI group (P = NS).

Conclusions

The addition of 0.2 mg epinephrine to the intrathecal combination of sufentanil and bupivacaine significantly prolonged labor analgesia without causing adverse effects to the mother or fetus. The intrathecal combination of sufentanil and bupivacaine, with or without epinephrine, provided rapid, profound labor analgesia and allowed most patients to ambulate.
Acylcarnitine Chain Length Influences Carnitine-enhanced Drug Flux through the Spinal Meninges
Authors: Ummenhofer Wolfgang C. , Bernards Christopher M.
Published: November 2003

Background

Palmitoyl carnitine has been shown to improve the penetration of hydrophilic drugs through the spinal meninges. Naturally occurring acylcarnitines, however, exist as a homologous series of different acyl chain lengths. The purpose of this study was to determine the most effective acylcarnitine chain length to increase meningeal permeability.

Methods

The transmeningeal flux of mannitol, morphine, and sufentanil through monkey spinal meninges was determined before and after adding acylcarnitines with chain lengths of 6 to 18 carbon atoms. Flux was measured using a previously established in vitro diffusion cell model.

Results

For mannitol, acylcarnitines generally showed a greater penetration-enhancing effect with increasing chain length, with palmitoyl carnitine (16 carbons) being the most effective compound with an increase of 244 +/- 29% (means +/- SE). Morphine flux was increased most significantly by lauroyl-(12 carbons) and myristoyl-carnitine (14 carbons) with 165 +/- 25% and 188 +/- 44% flux increases, respectively. In contrast, none of the studied acylcarnitines significantly altered the meningeal penetration of the more hydrophobic drug sufentanil.

Conclusions

The results suggest that, to promote hydrophilic drug penetration, acylcarnitines must surpass a critical chain length (10 carbon units) but should not exceed 16 carbon units. The activity of the acylcarnitines at the spinal meninges is reduced on either side of this range. The ability of acylcarnitines to increase the transmeningeal flux of morphine in vitro suggests that lauroyl or myristoyl carnitine may increase the spinal bioavailability of morphine after epidural administration.
Lack of Nonshivering Thermogenesis in Infants Anesthetized with Fentanyl and Propofol
Authors: Plattner Olga , Semsroth Margot , Sessler Daniel I. , Papousek Angelika , Klasen Christoph , Wagner Oswald
Published: November 2003

Background

Sweating, vasoconstriction, and shivering have been observed during general anesthesia. Among these, vasoconstriction is especially important because-once triggered-it minimizes further hypothermia. Surprisingly, the core-temperature plateau associated with vasoconstriction appears to preserve core temperature better in infants and children than adults. This observation suggests that vasoconstriction in anesthetized infants may be accompanied by hypermetabolism. Consistent with this theory, unanesthetized infants rely on nonshivering thermogenesis to double heat production when vasoconstriction alone is insufficient. Accordingly, the authors tested the hypothesis that intraoperative core hypothermia triggers nonshivering thermogenesis in infants.

Methods

With Ethics Committee approval and written parental consent, the authors studied six infants undergoing abdominal surgery. All were aged 1 day to 9 months and weighed 2.4-9 kg. Anesthesia was maintained with propofol and fentanyl. The infants were mechanically ventilated and allowed to cool passively until core (distal esophageal) temperatures reached 34-34.5 degrees C. Oxygen consumption-the authors' index of metabolic rate-was recorded throughout cooling. Because nonshivering thermogenesis triples circulating norepinephrine concentrations, arterial blood was analyzed for plasma catecholamines at approximately 0.5 degree C intervals. Thermoregulatory vasoconstriction was evaluated using forearm-fingertip, skin-surface gradients, with gradients exceeding 4 degrees C, indicating intense vasoconstriction. The patients were subsequently rapidly rewarmed to 37 degrees C. Regression analysis was used to correlate changes in oxygen consumption and plasma catecholamine concentrations with core temperature.

Results

All patients were vasoconstricted by the time core temperature reached 36 degrees C. Further reduction in core temperature to 34-34.5 degrees C did not increase oxygen consumption. Instead, oxygen consumption decreased linearly. Hypothermia also failed to increase plasma catecholamine concentrations.

Conclusions

Even at core temperatures approximately 2 degrees C below the vasoconstriction threshold, there was no evidence of nonshivering thermogenesis. This finding is surprising because all other major thermoregulatory responses have been detected during anesthesia. Infants and children thus appear similar to adults in being unable to increase metabolic rate in response to mild intraoperative hypothermia.
Changes in the Position of Epidural Catheters Associated with Patient Movement
Authors: Hamilton Catherine L. , Riley Edward T. , Cohen Sheila E.
Published: November 2003

Background

Epidural catheter movement has been noted with change of patient position and can result in inadequate anesthesia. This study was designed to measure movement and to develop a technique that minimizes catheter displacement.

Methods

In 255 parturients requesting epidural anesthesia for labor or cesarean section, a multiorificed lumbar epidural catheter was inserted with the patient in the sitting flexed position. The distance to the epidural space, length of catheter inserted, and amount of catheter position change as the patient moved from the sitting flexed to sitting upright and then to the lateral decubitus position were measured before the catheter was secured to the skin. Adequacy of analgesia, the need for catheter manipulation, and whether the patient was considered obese were noted. Data were grouped according to body mass index (BMI): < 25, 25-30, and > 30 kg/m2.

Results

The groups did not differ with respect to the length of catheter initially inserted or changes in catheter position between initial taping and removal. The distance to the epidural space differed significantly among the groups, increasing with greater BMI. Catheters frequently appeared to be drawn inward with position change from the sitting flexed to lateral decubitus position, with the greatest change seen in patients with BMI > 30. Only nine catheters were associated with inadequate analgesia, four of which were replaced. No analgesic failures occurred in the BMI > 30 group. In patients judged by the anesthesiologist to be obese or to have an obese back, BMI was greater, and distance to the epidural space and the magnitude of catheter movement with position change were greater than in those who were not obese.

Conclusions

Epidural catheters moved a clinically significant amount with reference to the skin in all BMI groups as patients changed position. If catheters had been secured to the skin before position change, many would have been pulled partially out of the epidural space. To minimize the risk of catheter displacement, particularly in obese patients, we recommend that multiorificed catheters be inserted at least 4 cm into the epidural space and that patients assume the sitting upright or lateral position before securing the catheter to the skin.
The Ventilation-Perfusion Relation and Gas Exchange in Mitral Valve Disease and Coronary Artery Disease Implications for Anesthesia, Extracorporeal Circulation, and Cardiac Surgery
Authors: Hachenberg Thomas , Arne Tenling , Hans Hansson E. , Hans Tyden , Goran Hedenstierna
Published: November 2003

Background

Patients with mitral valve disease (MVD) are at greater risk for respiratory complications after cardiac surgery compared with patients with coronary artery disease (CAD). The authors hypothesized that ventilation-perfusion (VA/Q) inequality is more pronounced in patients with MVD before and after induction of anesthesia and during and after surgery when extracorporeal circulation (ECC) is used.

Methods

In patients with MVD (n = 12) or with CAD (n = 12), VA/Q distribution was determined using the multiple inert gas elimination technique. Intrapulmonary shunt (Qs/Qr) defined as regions with VA/Q < 0.005 [% of total perfusion (Qr)], perfusion of "low" VA/Q areas (0.005 < or = VA/Q < 0.1, [% of Qr]), ventilation of "high" VA/Q regions (10 < or = VA/Q < or = 100 [% of total ventilation VE]), and dead space (VA/Q > 100 [% of VE]) were calculated from the retention/excretion data of the inert gases. Recordings were obtained while patients spontaneously breathed air in the awake state, during mechanical ventilation after induction of anesthesia, after separation of patients from ECC, and 4 h after operation.

Results

Qs/Qr was low in the awake state (MVD group, 3% +/- 3%; CAD group, 3% +/- 4%) and increased after induction of anesthesia to 10% +/- 8% (MVD group, P < 0.05) and 11% +/- 7% (CAD group, P < 0.01). Qs/Qr increased further after separation from ECC (MVD group, 24% +/- 9%, P < 0.01; CAD group, 23% +/- 7%, P < 0.01). Similarly, alveolar-arterial oxygen tension difference (PA-aO2) increased from 168 +/- 54 mmHg (anesthetized state) to 427 +/- 138 mmHg after ECC (MVD group, P < 0.01) and from 153 +/- 65 mmHg to 377 +/- 101 mmHg (CAD group, P < 0.01). In both groups, PA-aO2 was correlated with Qs/Qr. Four hours after operation, Qs/Qr had decreased significantly to 8% +/- 6% (CAD group) and 10% +/- 6% (MVD group). PA-aO2 and Qs/Qr showed no significant differences between the CAD and MVD groups.

Conclusions

Qs/Qr is the main pathophysiologic mechanism of gas exchange impairment during cardiac surgery for MVD or CAD. Impairment of pulmonary gas exchange secondary to general anesthesia, cardiac surgery, and ECC are comparable for patients undergoing myocardial revascularization or mitral valve surgery.
Bispectral Analysis Measures Sedation and Memory Effects of Propofol, Midazolam, Isoflurane, and Alfentanil in Healthy Volunteers
Authors: Glass Peter S. , Bloom Marc , Kearse Lee , Rosow Carl , Sebel Peter , Manberg Paul
Published: November 2003

Background

The bispectral index (BIS), a value derived from the electroencephalograph (EEG), has been proposed as a measure of anesthetic effect. To establish its utility for this purpose, it is important to determine the relation among BIS, measured drug concentration, and increasing levels of sedation. This study was designed to evaluate this relation for four commonly used anesthetic drugs: propofol, midazolam, isoflurane, and alfentanil.

Methods

Seventy-two consenting volunteers were studied at four institutions. Volunteers were given either isoflurane, propofol, midazolam, or alfentanil. Each volunteer was administered a dose-ranging sequence of one of the study drugs to achieve predetermined target concentrations. A frontal montage was used for continuous recording of the EEG. At each pseudo-steady-state drug concentration, a BIS score was recorded, the participant was shown either a picture or given a word to recall, an arterial blood sample was obtained for subsequent analysis of drug concentration, and the participant was evaluated for level of sedation as determined by the responsiveness portion of the observer's assessment of the alertness/ sedation scale (OAAS). An OAAS score of 2 or less was considered unconscious. The BIS (version 2.5) score was recorded in real-time and the BIS (version 3.0) was subsequently derived off-line from the recorded raw EEG data. The relation among BIS, measured drug concentration, responsiveness score, and presence or absence of recall was determined by linear and logistic regression for both the individual drugs and, when appropriate, for the pooled results. The prediction probability was also calculated.

Results

The BIS score (r = 0.883) correlated significantly better than the measured propofol concentration (r = -0.778; P < 0.05) with the responsiveness score. The BIS provided as effective correlation with responsiveness score of the OAAS as did the measured concentration for midazolam and isoflurane. None of the volunteers given alfentanil lost consciousness and thus were excluded from the pooled analysis. The pooled BIS values at which 50% and 95% of participants were unconscious were 67 and 50, respectively. The prediction probability values for BIS ranged from 0.885-0.976, indicating a very high predictive performance for correctly indicating probability of loss of consciousness.

Conclusions

The BIS both correlated well with the level of responsiveness and provided an excellent prediction of the loss of consciousness. These results imply that BIS may be a valuable monitor of the level of sedation and loss of consciousness for propofol, midazolam, and isoflurane.
Isoflurane-induced Cerebral Hyperemia in Neuronal Nitric Oxide Synthase Gene Deficient Mice
Authors: Okamoto Hirotsugu , Meng Wei , Ma Jinya , Ayata Cenk , Roman Richard J. , Bosnjak Zeljko J. , Kampine John P. , Huang Paul L. , Moskowitz Michael A. , Hudetz Antal G.
Published: November 2003

Background

Nitric oxide (NO) has been reported to play an important role in isoflurane-induced cerebral hyperemia in vivo. In the brain, there are two constitutive isoforms of NO synthase (NOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). Recently, the mutant mouse deficient in nNOS gene expression (nNOS knockout) has been developed. The present study was designed to examine the role of the two constitutive NOS isoforms in cerebral blood flow (CBF) response to isoflurane using this nNOS knockout mouse.

Methods

Regional CBF (rCBF) in the cerebral cortex was measured with laser-Doppler flowmetry in wild-type mice (129/SV or C57BL/6) and nNOS knockout mice during stepwise increases in the inspired concentration of isoflurane from 0.6 vol% to 1.2, 1.8, and 2.4 vol%. Subsequently, a NOS inhibitor, N omega-nitro-L-arginine (L-NNA), was administered intravenously (20 mg/kg), and 45 min later, the rCBF response to isoflurane was tested again. In separate groups of wild-type mice and the knockout mice, the inactive enantiomer, N omega-nitro-D-arginine (D-NNA) was administered intravenously in place of L-NNA. Brain NOS activity was measured with radio-labeled L-arginine to L-citrulline conversion after treatment with L-NNA and D-NNA.

Results

Isoflurane produced dose-dependent increases in rCBF by 25 +/- 3%, 74 +/- 10%, and 108 +/- 14% (SEM) in 129/SV mice and by 32 +/- 2%, 71 +/- 3%, and 96 +/- 7% in C57BL/6 mice at 1.2, 1.8, and 2.4 vol%, respectively. These increases were attenuated at every anesthetic concentration by L-NNA but not by D-NNA. Brain NOS activity was decreased by 92 +/- 2% with L-NNA compared with D-NNA. In nNOS knockout mice, isoflurane increased rCBF by 67 +/- 8%, 88 +/- 12%, and 112 +/- 18% at 1.2, 1.8, and 2.4 vol%, respectively. The increase in rCBF at 1.2 vol% was significantly greater in the nNOS knockout mice than that in the wild-type mice. Administration of L-NNA in the knockout mice attenuated the rCBF response to isoflurane at 1.2 and 1.8 vol% but had no effect on the response at 2.4 vol%.

Conclusions

In nNOS knockout mice, the cerebral hyperemic response to isoflurane is preserved by compensatory mechanism(s) that is NO-independent at 2.4 vol%, although it may involve eNOS at 1.2 and 1.8 vol%. It is suggested that in wild-type mice, eNOS and nNOS contribute to isoflurane-induced increase in rCBF. At lower concentrations (1.2 and 1.8 vol%), eNOS may be involved, whereas at 2.4 vol%, nNOS may be involved.
Compound A Induces Sister Chromatid Exchanges in Chinese Hamster Ovary Cells
Authors: Eger Edmond I. , Laster Michael J. , Winegar Richard , Han Christine , Gong Diane
Published: November 2003

Background

Compound A [CF2 = C(CF3)OCH2F], a degradation product of sevoflurane [(CF3)2CHOCH2F], is a vinyl ether and may be an alkylating agent. Thus it is a potential genotoxin.

Methods

The capacity of compound A to produce sister chromatid exchanges was measured in Chinese hamster ovary cells with and without metabolic activation. Concentrations of 11 to 468 ppm compound A were applied for 2 h, the Chinese hamster ovary cells were incubated for a further 34 h in the presence of bromodeoxyuridine, and then colcemid was added to produce arrest in metaphase. Coded slides of cells were examined blindly, and 50 chromosome spreads were counted for each test concentration.

Results

The lowest concentration of compound A applied without metabolic activator (27 ppm) significantly increased (P < 0.001) sister chromatid exchanges, and increasing concentrations of compound A increased the incidence of exchanges. Metabolic activation did not increase the incidence of exchanges.

Conclusions

Compound A increases sister chromatid exchanges at concentrations (27 ppm) obtained in low-flow systems when sevoflurane is used at concentrations approximating minimum alveolar concentration.
Isoflurane Anesthesia Attenuates Endothelium-dependent Pulmonary Vasorelaxation by Inhibiting the Synergistic Interaction between Nitric Oxide and Prostacyclin
Authors: Gambone Linda M. , Murray Paul A. , Flavahan Nicholas A.
Published: November 2003

Background

Endothelium-derived nitric oxide causes vasodilation in part by increasing the dilator activity of other endothelium-derived mediators, including prostacyclin and a K+ATP channel-dependent hyperpolarizing factor. Although previous studies have proposed that isoflurane (ISO) depresses endothelium-dependent vasorelaxation by inhibiting endothelium-derived nitric oxide activity, the effects of ISO on the interactions among endothelium-derived dilators have not been characterized. The aim of this study was to determine the mechanisms underlying the inhibitory effect of ISO on endothelium-dependent relaxation in canine pulmonary arteries. Specifically, the goal was to assess the effects of ISO on the individual actions and on the synergistic interactions of these endothelium-derived mediators.

Methods

Canine pulmonary arterial rings were suspended for isometric tension recording. The effects of 1 minimum alveolar concentration ISO (0.4 mM) on vasorelaxation responses to bradykinin, A23187, acetylcholine, cromakalim, and SIN-1 were assessed in phenylephrine-precontracted rings with and without pretreatment with a nitric oxide synthase inhibitor (N omega-nitro-L-arginine methyl ester; L-NAME), a cyclooxygenase inhibitor (indomethacin), or a K+ATP channel inhibitor (glybenclamide).

Results

Isofluane attenuated pulmonary vasorelaxation induced by bradykinin, A23187, and cromakalim but had no effect on relaxation induced by acetylcholine or SIN-1. Neither the nitric oxide-mediated nor the prostacyclin-mediated components of relaxation induced by bradykinin and A23187 were altered by ISO. However, ISO abolished the K+ATP-mediated component of relaxation and the K+ATP-dependent synergistic interaction between nitric oxide and prostacyclin.

Conclusions

These results suggest that ISO selectively attenuates endothelium-dependent relaxation in canine pulmonary arteries. It exerts its inhibitory effect by interfering with a synergistic interaction between nitric oxide and prostacyclin, possibly via an effect on K+ATP channels.
Hyperbaric Dye Solution Distribution Characteristics after Pencil-point Needle Injection in a Spinal Cord Model
Authors: Holman Stephen J. , Robinson Ronald A. , Beardsley David , Stewart Sandy F. C. , Klein Leonard , Stevens Rom A.
Published: November 2003

Background

The flow-rate limiting and directional characteristics of caudally directed microcatheters, which lead to intrathecal maldistribution of hyperbaric 5% lidocaine, are believed to have contributed to at least 11 cases of cauda equina syndrome. The authors investigated the distribution characteristics of hyperbaric dye solutions via caudally directed side port needles at various rates of injection in a spinal cord model to determine the potential for maldistribution.

Methods

Using a digital video image processing technique, we injected a hyperbaric solution of phthalocyanine blue dye through caudally directed side-port needles into a supinely oriented transparent spinal canal model filled with simulated cerebrospinal fluid. Injections via commonly used spinal needles (24-gauge and 25-gauge Sprotte, and 25-gauge and 27-gauge Whitacre) were recorded using five injection rates (2, 4, 6, 8, and 16 ml/min).

Results

For all needles tested, injection rate had a significant effect on the peak dye concentration (P < 0.0001). Injection rates > or = 6 ml/min (2 ml/20 s) resulted in peak dye concentrations of less than 168 mg/1 (extrapolated concentration of 1% lidocaine). Injection via the 24-gauge Sprotte needle, which has a larger orifice area and internal diameter, resulted in significantly lower peak dye concentrations than via the smaller Whitacre needles tested (P < 0.05).

Conclusions

Sacral maldistribution could be minimized by using injection rates > or = 6 ml/min (2 ml/20 s), for all of the side-port spinal needles used in this model study. When very slow injection rates (2 ml/min) are used, peak dye concentrations varied inversely and significantly with needle internal diameter and orifice area.