bluuebunny/crossref_metadata_2025 huggingface dataset:
Auditory Evoked Potential Index Predicts the Depth of Sedation and Movement in Response to Skin Incision during Sevoflurane Anesthesia
Authors: Kurita Tadayoshi , Doi Matsuyuki , Katoh Takasumi , Sano Hideki , Sato Shigehito , Mantzaridis Haralambos , Kenny Gavin N. C.
Published: November 2003

Background

The auditory evoked potential (AEP) index, which is a single numerical parameter derived from the AEP in real time and which describes the underlying morphology of the AEP, has been studied as a monitor of anesthetic depth. The current study was designed to evaluate the accuracy of AEPindex for predicting depth of sedation and anesthesia during sevoflurane anesthesia.

Methods

In the first phase of the study, a single end-tidal sevoflurane concentration ranging from 0.5 to 0.9% was assigned randomly and administered to each of 50 patients. The AEPindex and the Bispectral Index (BIS) were obtained simultaneously. Sedation was assessed using the responsiveness portion of the observer's assessment of alertness-sedation scale. In the second phase of the study, 10 additional patients were included, and the 60 patients who were scheduled to have skin incisions were observed for movement in response to skin incision at the end-tidal sevoflurane concentrations between 1.6 and 2.6%. The relation among AEPindex, BIS, sevoflurane concentration, sedation score, and movement or absence of movement after skin incision was determined. Prediction probability values for AEPindex, BIS, and sevoflurane concentration to predict depth of sedation and anesthesia were also calculated.

Results

The AEPindex, BIS, and sevoflurane concentration correlated closely with the sedation score. The prediction probability values for AEPindex, BIS, and sevoflurane concentration for sedation score were 0.820, 0.805, and 0.870, respectively, indicating a high predictive performance for depth of sedation. AEPindex and sevoflurane concentration successfully predicted movement after skin (prediction probability = 0.910 and 0.857, respectively), whereas BIS could not (prediction probability = 0.537).

Conclusions

Auditory evoked potential index can be a guide to the depth of sedation and movement in response to skin incision during sevoflurane anesthesia.
A New Model of Electrically Evoked Pain and Hyperalgesia in Human Skin
Authors: Koppert Wolfgang , Dern Sara K. , Sittl Reinhard , Albrecht Sven , Schüttler Jürgen , Schmelz Martin
Published: November 2003

Background

The authors used the analgesics alfentanil, S(+)-ketamine, and systemic lidocaine to examine a new human model of experimental pain and hyperalgesia.

Methods

Transcutaneous electrical stimulation at a high current density (5 Hz, 67.5+/-6.6 mA) was used to provoke acute pain (numeric rating scale, 5 of 10), stable areas of secondary mechanical hyperalgesia to pin prick (43.6+/-32.1 cm2), and light touch (27.5+/-16.2 cm2) for 2 h. Alfentanil, S(+)-ketamine, and lidocaine were applied for 20 min in a double-blind, placebo-controlled, crossover design in 12 subjects using target controlled infusions.

Results

In the placebo session, pain ratings and areas of hyperalgesia were stable during the stimulation period, which facilitated the assessment of analgesic effects. Alfentanil effectively inhibited electrically evoked pain and reduced pin prick hyperalgesia and allodynia during its infusion. S(+)-ketamine-induced inhibition of secondary hyperalgesia was more pronounced and lasted for the whole experimental protocol. Therapeutic levels of systemic lidocaine showed only marginal analgesic effects, but lasting antihyperalgesic effects.

Conclusions

A new model of electrically induced pain and hyperalgesia was established, which enabled assessment of the time course of analgesic and antihyperalgesic effects with high temporal resolution and minimum tissue damage and which was further validated by use of common intravenous anesthetics.
Inflammatory Pain and Hypersensitivity Are Selectively Reversed by Epidural Bupivacaine and Are Developmentally Regulated
Authors: Howard Richard F. , Hatch David J. , Cole Timothy J. , Fitzgerald Maria
Published: November 2003

Background

Low doses of local anesthetics applied to the young rat spinal cord in vitro have been shown to inhibit C-fiber-evoked responses. The aim of this work was to investigate whether such low doses applied epidurally selectively reduce nociceptive responses in vivo and to investigate the influence of postnatal development on such local anesthetic actions.

Methods

Three groups of rat pups aged 3, 10, and 21 days were studied. The threshold of the flexion withdrawal reflex to mechanical stimulation was determined in the hind limb at each age. Inflammatory pain was induced in the right hind limb with 2% carrageenan, causing a reduction in the sensory threshold on that side. The difference in threshold between the two sides represents inflammatory hypersensitivity. The effect of low-dose epidural bupivacaine on sensory thresholds and thus the induced hypersensitivity was also determined for each age group.

Results

Inflammatory hypersensitivity was selectively attenuated by very low doses of bupivacaine (concentration range. 0.004-0.0625%), which did not affect the sensory threshold in the contralateral uninflamed limb. This effect was also age-related, with younger rats being more sensitive than older rats.

Conclusions

The effects of epidural bupivacaine in the infant rat are developmentally regulated. Lower doses have a selective analgesic effect that decreases with increasing postnatal age.
Increased Sensitivity to Depolarizing and Nondepolarizing Neuromuscular Blocking Agents in Young Rat Hemidiaphragms
Authors: Fortier L. Philippe , Robitaille Richard , Donati François
Published: November 2003

Background

Newborn neuromuscular junctions are more sensitive to d-tubocurarine than more mature preparations. It is unclear whether the same modifications occur with newer nondepolarizing agents and depolarizing agent succinylcholine. The purpose of this study was to determine the relative sensitivity of newborn neuromuscular junctions to succinylcholine and five nondepolarizing agents.

Methods

The phrenic nerve-hemidiaphragm preparation from 60 rats was used, 30 aged 9-12 days (newborn) and 30 aged 27-33 days (adult). Five rats from each group were exposed to one of six neuromuscular blocking agents (d-tubocurarine, cisatracurium, atracurium, vecuronium, rocuronium, and succinylcholine). Indirectly elicited twitch tension was measured during control conditions in the absence of blocking agent, followed by four concentrations of one of the six agents. Concentration-response curves were constructed and the EC50 (concentration required to produce 50% depression of twitch tension) was obtained. Potency ratios (EC50adult/EC50newborn) were derived for each agent.

Results

Newborn preparations were significantly (P < 0.001) more sensitive than their adult counterparts for all six agents tested. For nondepolarizing agents, the potency ratio was in the 6-12 range. The EC50adult/EC50newborn were as follows, in decreasing potency order: d-tubocurarine, 1.68/0.23 microM; cisatracurium, 2.73/0.47 microM; vecuronium, 5.47/0.59 microM; rocuronium, 9.7/0.78 microM; and atracurium, 12.3/1.9 microM. Succinylcholine was three times as potent in newborn rats, with an EC50adult/EC50newborn of 21.3/7.3 microM. The ratio for succinylcholine was significantly less than for all nondepolarizing drugs (P < 0.02).

Conclusion

The newborn neuromuscular junction of the rat shows an increased sensitivity to all neuromuscular blocking agents tested, including succinylcholine. However, the potency ratio was greater for nondepolarizing than depolarizing drugs. The optimal dose of these agents for certain situations such as cesarean section and anesthesia in neonates should be reassessed.
Effects of Sevoflurane on Excitatory Neurotransmission to Medullary Expiratory Neurons and on Phrenic Nerve Activity in a Decerebrate Dog Model
Authors: Stucke Astrid G. , Stuth Eckehard A. E. , Tonkovic-Capin Viseslav , Tonkovic-Capin Mislav , Hopp Francis A. , Kampine John P. , Zuperku Edward J.
Published: November 2003

Background

Sevoflurane is a new volatile anesthetic with a pronounced respiratory depressant effect. Synaptic neurotransmission in canine expiratory bulbospinal neurons is mainly mediated by excitatory N-methyl-D-aspartatic acid (NMDA) receptor input and modulated by inhibitory gamma-aminobutyric acid type A (GABA(A)) receptors. The authors investigated the effect of sevoflurane on these mechanisms in decerebrate dogs.

Methods

Studies were performed in decerebrate, vagotomized, paralyzed and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of 1 minimum alveolar concentration (MAC; 2.4%) sevoflurane on extracellularly recorded neuronal activity was measured during localized picoejection of the glutamate agonist NMDA and the GABA(A) receptor blocker bicuculline in a two-part protocol. First, complete blockade of the GABA(A)ergic mechanism by bicuculline allowed differentiation between the effects of sevoflurane on overall GABA(A)ergic inhibition and on overall glutamatergic excitation. In a second step, the neuronal response to exogenous NMDA was used to estimate sevoflurane's effect on postsynaptic glutamatergic neurotransmission.

Results

One minimum alveolar concentration sevoflurane depressed the spontaneous activity of 16 expiratory neurons by 36.7+/-22.4% (mean +/- SD). Overall glutamatergic excitation was depressed 19.5+/-16.2%, and GABA(A)ergic inhibition was enhanced 18.7+/-20.6%. However, the postsynaptic response to exogenous NMDA was not significantly altered. In addition, 1 MAC sevoflurane depressed peak phrenic nerve activity by 61.8+/-17.7%.

Conclusions

In the authors' in vivo expiratory neuronal model, the depressive effect of sevoflurane on synaptic neurotransmission was caused by a reduction of presynaptic glutamatergic excitation and an enhancement of GABA(A)ergic inhibition. The effects on expiratory neuronal activity were similar to halothane, but sevoflurane caused a stronger depression of phrenic nerve activity than halothane.
Spinal Endogenous Acetylcholine Contributes to the Analgesic Effect of Systemic Morphine in Rats
Authors: Chen Shao-Rui , Pan Hui-Lin
Published: November 2003

Background

Systemic morphine is known to cause increased release of acetyicholine in the spinal cord. Intrathecal injection of the cholinergic receptor agonists or acetyicholinesterase inhibitors produces antinociception in both animals and humans. In the present study, we explored the functional importance of spinal endogenous acetylcholine in the analgesic action produced by intravenous morphine.

Methods

Rats were implanted with intravenous and intrathecal catheters. The antinociceptive effect of morphine was determined by the paw-withdrawal latency in response to a radiant heat stimulus after intrathecal treatment with atropine (a muscarinic receptor antagonist), mecamylamine (a nicotinic receptor antagonist), or cholinergic neurotoxins (ethylcholine mustard aziridinium ion [AF64A] and hemicholinium-3).

Results

Intravenous injection of 2.5 mg/kg morphine increased significantly the paw-withdrawal latency. Intrathecal pretreatment with 30 microg atropine (n = 7) or 50 microg mecamylamine (n = 6) both attenuated significantly the antinociceptive effect of morphine. The inhibitory effect of atropine on the effect of morphine was greater than that of mecamylanilne. Furthermore, the antinociceptive effect of morphine was significantly reduced in rats pretreated with intrathecal AF64A (n = 7) or hemicholinium-3 (n = 6) to inhibit the high-affinity choline transporter and acetylcholine synthesis. We found that intrathecal AF64A reduced significantly the [3H]hemicholinium-3 binding sites but did not affect its affinity in the dorsal spinal cord.

Conclusions

The data in the current study indicate that spinal endogenous acetylcholine plays an important role in mediating the analgesic effect of systemic morphine through both muscarinic and nicotinic receptors.
Dose-dependent Enhancement of In Vivo GABAA–Benzodiazepine Receptor Binding by Isoflurane
Authors: Gyulai Ferenc E. , Mintun Mark A. , Firestone Leonard L.
Published: November 2003

Background

Abundant in vitro and animal model data suggest the postsynaptic gamma-aminobutyric acid receptor type A (GABA(A)-R) is an important target for volatile general anesthetics, but the relevance of these models is untested in humans. Because benzodiazepines have also been shown to act via a specific GABA(A)-R site, they provide sensitive probes for the GABA(A)-R. Availability of the 11C-labeled benzodiazepine ligand, flumazenil, allowed us to quantitatively test in humans whether the volatile anesthetic isoflurane affects GABA(A)-Rs in vivo in a dose-dependent manner.

Methods

11C-flumazenil positron emission tomography scans were obtained in 12 healthy subjects while awake (control condition) and anesthetized with either 1.0 or 1.5 minimum alveolar concentration isoflurane (n = 7 and 5, respectively; isoflurane conditions). Regions of interest included areas of high, intermediate, and low GABA(A)-benzodiazepine site density. For each subject and experimental condition, the binding of 11C-flumazenil, expressed as distribution volume (which linearly correlates to maximal binding site density and apparent ligand affinity), was obtained by curve fitting using a two-compartment model.

Results

The ratio of distribution volume increased significantly in each examined region during the isoflurane conditions compared with control conditions (P < 0.01, one-tailed t test). Furthermore, the increases in ratio of distribution volume during the 1.5-minimum alveolar concentration isoflurane condition were significantly greater than those measured during 1.0 minimum alveolar concentration isoflurane inhalation (P < 0.002, one-tailed t test).

Conclusions

Isoflurane exposure appeared to enhance receptor-specific 11C-flumazenil binding in a dose-dependent manner. The results suggest the possibility that a conformational change of the GABA(A)-R is involved in the mechanism of action of isoflurane in the living human brain.
Different Patterns of Mast Cell Activation by Muscle Relaxants in Human Skin
Authors: Koppert Wolfgang , Blunk James A. , Petersen Lars J. , Skov Per , Rentsch Katharina , Schmelz Martin
Published: November 2003

Background

Activation of mast cells and systemic release of histamine are major side effects of intravenously administered muscle relaxants. In the current study, dermal microdialysis was used for the investigation of mast cell activation by muscle relaxants. Dermal microdialysis enabled simultaneous assessment of mediator release, vascular reactions, and sensory effects induced by intradermal application of muscle relaxants without systemic side effects.

Methods

Succinylcholine, the isoquinolines cisatracurium, atracurium, and mivacurium, and the steroids pancuronium, vecuronium, rocuronium, and rapacuronium were tested in human volunteers (n = 6 each). After intradermal insertion of microdialysis capillaries (0.4 mm diameter, cutoff 3,000 kd) and a 60-min equilibration period, the muscle relaxants were delivered via the capillaries for 30 min, followed by a 30-min washout period. Dialysate was sampled at 15-min intervals, and histamine, mast cell tryptase, and protein extravasation were determined. Changes in skin blood flow were measured using a laser Doppler imager. Potency and efficacy were derived from nonlinear fittings of the dose-response curves.

Results

For succinylcholine and the isoquinolines, dose-response curves for the vascular and sensory effects paralleled the histamine and tryptase release. In contrast, aminosteroids evoked a rapid histamine release that was accompanied by a delayed increase in tryptase.

Conclusions

Dermal microdialysis has been successfully used to simultaneously assess mediator release, vascular reactions, and sensory effects. The different pattern of tryptase release by isoquinolines and aminosteroids suggests different mechanisms of mast cell activation.
Low-concentration Lidocaine Rapidly Inhibits Axonal Transport in Cultured Mouse Dorsal Root Ganglion Neurons
Authors: Kanai Akifumi , Hiruma Hiromi , Katakura Takashi , Sase Sumi , Kawakami Tadashi , Hoka Sumio
Published: November 2003

Background

Axonal transport plays a critical role in supplying materials for a variety of neuronal functions such as morphogenetic plasticity, synaptic transmission, and cell survival. In the current study, the authors investigated the effects of the analgesic agent lidocaine on axonal transport in neurites of cultured mouse dorsal root ganglion neurons. In relation to their effects, the effects of lidocaine on the growth rate of the neurite were also examined.

Methods

Isolated mouse dorsal root ganglion cells were cultured for 48 h until full growth of neurites. Video-enhanced microscopy was used to observe particles transported within neurites and to measure the neurite growth during control conditions and in the presence of lidocaine.

Results

Application of 30 microM lidocaine immediately reduced the number of particles transported in anterograde and retrograde axonal directions. These effects were persistently observed during the application (26 min) and were reversed by lidocaine washout. The inhibitory effect was dose-dependent at concentrations from 0.1 to 1,000 microM (IC50 = 10 microM). In Ca2+-free extracellular medium, lidocaine failed to inhibit axonal transport. Calcium ionophore A23187 (0.1 microM) reduced axonal transport in both directions. The inhibitory effects of lidocaine and A23187 were abrogated by 10 microM KN-62, a Ca2+-calmodulin-dependent protein kinase II inhibitor. Application of such low-concentration lidocaine (30 microM) for 30 min reduced the growth rate of neurites, and this effect was also blocked by KN-62.

Conclusions

Low-concentration lidocaine rapidly inhibits axonal transport and neurite growth via activation of calmodulin-dependent protein kinase II.
Minimum Alveolar Concentration of Volatile Anesthetics in Rats during Postnatal Maturation
Authors: Orliaguet Gilles , Vivien Benoît , Langeron Olivier , Bouhemad Belaid , Coriat Pierre , Riou Bruno
Published: November 2003

Background

Although neonatal rats have become widely used as experimental laboratory animals, minimum alveolar concentration (MAC) values of volatile anesthetics in rats during postnatal maturation remain unknown.

Methods

We determined MAC values of volatile anesthetics in spontaneously breathing neonatal (2-, 9-, and 30-day-old) and adult Wistar rats exposed to increasing (in 0.1-0.2% steps) concentrations of halothane, isoflurane, or sevoflurane (n = 12-20 in each group), using the tail-clamp technique. MAC and its 95% confidence intervals were calculated using logistic regression and corrected for body temperature (37 degrees C).

Results

In adult rats, inspired MAC values corrected at 37 degrees C were as follows: halothane, 0.88% (confidence interval, 0.82-0.93%); isoflurane, 1.12% (1.07-1.18%); and sevoflurane, 1.97% (1.84-2.10%). In 30-day-old rats, the values were as follows: halothane, 1.14% (1.07-1.20%); isoflurane, 1.67% (1.58-1.76%); and sevoflurane, 2.95% (2.75-3.15%). In 9-day-old rats, inspired MAC values were as follows: halothane, 1.68% (1.58-1.78%); isoflurane, 2.34% (2.21-2.47%); and sevoflurane, 3.74% (3.64-3.86%). In 2-day-old rats, inspired MAC values were as follows: halothane, 1.54% (1.44-1.64%); isoflurane, 1.86% (1.72-2.01%); and sevoflurane, 3.28% (3.09-3.47%).

Conclusion

As postnatal age increases, MAC value significantly increases, reaching the greatest value in 9-day-old rats, and decreases thereafter, and at 30 days is still greater than the adult MAC value.
Comparison of Two Different Temperature Maintenance Strategies during Open Abdominal Surgery
Authors: Janicki Piotr K. , Higgins Michael S. , Janssen Jill , Johnson Raymond F. , Beattie Charles
Published: November 2003

Background

A new system has been developed that circulates warm water through a whole body garment worn by the patient during surgery. In this study the authors compared two different strategies for the maintenance of intraoperative normothermia. One strategy used a new water garment warming system that permitted active warming of both the upper and lower extremities and the back. The other strategy used a single (upper body) forced-air warming system.

Methods

In this prospective, randomized study, 53 adult patients were enrolled in one of two intraoperative temperature management groups during open abdominal surgery with general anesthesia. The water-garment group (n = 25) received warming with a body temperature (rectal) set point of 36.8 degrees C. The forced-air-warmer group (n = 28) received routine warming therapy using upper body forced-air warming system (set on high). The ambient temperature in the operating room was maintained constant at approximately 20 degrees C. Rectal, distal esophageal, tympanic, forearm, and fingertip temperatures were recorded perioperatively and during 2 h after surgery. Extubated patients in both groups were assessed postoperatively for shivering, use of additional warming devices, and subjective thermal comfort.

Results

The mean rectal and esophageal temperatures at incision, 1 h after incision, at skin closure, and immediately postoperatively were significantly higher (0.4-0.6 degrees C) in the group that received water-garment warming when compared with the group that received upper body forced-air warming. The calculated 95% confidence intervals for the above differences in core temperatures were 0.7-0.1, 0.8-0.2, 0.8-0.2, and 0.9-0.1, retrospectively. In addition, 14 and 7% of patients in the control upper body forced-air group remained hypothermic (< 35.5 degrees C) 1 and 2 h after surgery, respectively. No core temperature less than 35.5 degrees C was observed perioperatively in any of the patients from the water-garment group. A similar frequency of the thermal stress events (shivering, use of additional warming devices, subjective thermal discomfort) was observed after extubation in both groups during the 2 h after surgery.

Conclusions

The investigated water warming system, by virtue of its ability to deliver heat to a greater percentage of the body, results in better maintenance of intraoperative normothermia that does forced-air warming applied only to the upper extremities, as is common practice.
Respiratory Sites of Action of Propofol
Authors: Nieuwenhuijs Diederik , Sarton Elise , Teppema Luc J. , Kruyt Erik , Olievier Ida , van Kleef Jack , Dahan Albert
Published: November 2003

Background

Propofol has a depressant effect on metabolic ventilatory control, causing depression of the ventilatory response to acute isocapnic hypoxia, a response mediated via the peripheral chemoreflex loop. In this study, the authors examined the effect of sedative concentrations of propofol on the dynamic ventilatory response to carbon dioxide to obtain information about the respiratory sites of action of propofol.

Methods

In 10 healthy volunteers, the end-tidal carbon dioxide concentration was varied according to a multifrequency binary sequence that involved 13 steps into and 13 steps out of hypercapnia (total duration, 1,408 s). In each subject, two control studies, two studies at a plasma target propofol concentration of 0.75 microg/ml (P(low)), and two studies at a target propofol concentration of 1.5 microg/ml (P(high)) were performed. The ventilatory responses were separated into a fast peripheral component and a slow central component, characterized by a time constant, carbon dioxide sensitivity, and apneic threshold. Values are mean +/- SD.

Results

Plasma propofol concentrations were approximately 0.5 microg/ml for P(low) and approximately 1.3 mg/ml for P(high), Propofol reduced the central carbon dioxide sensitivity from 1.5 +/- 0.4 to 1.2 +/- 0.3 (P(low); P < 0.01 vs. control) and 0.9 +/- 0.1 l x min(-1) x mmHg(-1) (P(high); P < 0.001 vs. control). The peripheral carbon dioxide sensitivity remained unaffected by propofol (control, 0.5 +/- 0.3; P(low), 0.5 +/- 0.2; P(high), 0.5 +/- 0.2 l x min(-1) x mmHg(-1)). The apneic threshold was reduced from 36.3 +/- 2.7 (control) to 35.0 +/- 2.1 (P(low); P < 0.01 vs. control) and to 34.6 +/- 1.9 mmHg (P(high); P < 0.01 vs. control).

Conclusions

Sedative concentrations of propofol have an important effect on the control of breathing, showing depression of the ventilatory response to hypercapnia. The depression is attributed to an exclusive effect within the central chemoreflex loop at the central chemoreceptors. In contrast to low-dose inhalational anesthetics, the peripheral chemoreflex loop, when stimulated with carbon dioxide, remains unaffected by propofol.
Effects of Mild Hypothermia on Blood–Brain Barrier Disruption during Isoflurane or Pentobarbital Anesthesia
Authors: Chi Oak Za , Liu Xia , Weiss Harvey R.
Published: November 2003

Background

This study was performed to determine whether mild hypothermia (32 degrees C) could attenuate the degree of blood-brain barrier (BBB) disruption caused by a hyperosmolar solution and whether the degree of disruption would vary depending on anesthetic agents.

Methods

Rats were assigned to one of four groups: normothermic isoflurane, normothermic pentobarbital, hypothermic isoflurane, and hypothermic pentobarbital. During isoflurane (1.4%; normothermic or hypothermic) or pentobarbital (50 mg/kg administered intraperitoneally; normothermic or hypothermic) anesthesia, the external carotid artery and the femoral artery and vein were catheterized. Body temperature was maintained at 37 and 32 degrees C for the normothermic and hypothermic groups, respectively. To open the BBB, 25% mannitol was infused through the right carotid artery at the rate of 0.25 ml x kg(-1) x s(-1) for 30 s. The transfer coefficient of 14C-alpha-aminoisobutyric acid was determined.

Results

Blood pressure was similar among the four groups of animals. The degree of the BBB disruption by hyperosmolar mannitol was less with isoflurane than pentobarbital anesthesia in the normothermic groups (transfer coefficient: 29.9 +/- 17.1 and 50.4 +/- 17.5 microl x g(-1) x min(-1) for normothermic isoflurane and pentobarbital, respectively; P < 0.05). Mild hypothermia decreased the BBB disruption during anesthesia with both anesthetic agents (hypothermic isoflurane: 9.8 +/- 8.3 microl x g(-1) x min(-1), P < 0.05 vs. normothermic isoflurane; hypothermic pentobarbital: 30.2 +/- 13.9 microl x g(-1) x min(-1), P < 0.05 vs. normothermic pentobarbital), but the disruption was less during isoflurane anesthesia (hypothermic isoflurane vs. hypothermic pentobarbital, P < 0.005). In the contralateral cortex, there were no significant differences among these four experimental groups.

Conclusions

The data demonstrated that hypothermia was effective in attenuating BBB disruption by hyperosmolar mannitol during isoflurane as well as pentobarbital anesthesia. The degree of disruption appeared smaller during isoflurane than during pentobarbital anesthesia in both the normothermic as well as the hypothermic groups.
Antiallodynic Effect of Intrathecal Neostigmine Is Mediated by Spinal Nitric Oxide in a Rat Model of Diabetic Neuropathic Pain
Authors: Chen Shao-Rui , Khan Ghous M. , Pan Hui-Lin
Published: November 2003

Background

Intrathecal administration of acetylcholinesterase inhibitors produces antinociception in both animals and humans, but their effect on diabetic neuropathic pain has not been studied. In the current study, we determined the antiallodynic effect of intrathecal injection of an acetylcholinesterase inhibitor, neostigmine, in a rat model of diabetic neuropathic pain. In addition, since acetylcholine can increase release of nitric oxide in the spinal cord, we studied the role of spinal endogenous nitric oxide in the action of intrathecal neostigmine in diabetic neuropathic pain.

Methods

Rats were rendered diabetic with an intraperitoneal 50-mg/kg injection of streptozotocin. Intrathecal catheters were inserted, with tips in the lumbar intrathecal space. Mechanical allodynia was determined by application of von Frey filaments to the hind paw. We first determined the dose-dependent effect of intrathecal neostigmine on allodynia. The role of spinal nitric oxide in the action of intrathecal neostigmine was then examined through intrathecal treatments with a neuronal nitric oxide synthase inhibitor (TRIM), a nitric oxide scavenger (PTIO), L-arginine, or D-arginine.

Results

The diabetic rats developed a sustained tactile allodynia within 4 weeks after streptozotocin injection. Intrathecal injection of 0.1-0.5 microg neostigmine dose-dependently increased the withdrawal threshold in response to application of von Frey filaments. Intrathecal pretreatment with 30 microg TRIM or 30 microg PTIO abolished the antiallodynic effect of intrathecal neostigmine. Furthermore, the inhibitory effect of TRIM on the action of intrathecal neostigmine was reversed by intrathecal injection of 100 microg L-arginine but not D-arginine.

Conclusions

Intrathecal neostigmine produces a profound analgesic effect in a rat model of diabetic neuropathic pain. Spinal endogenous nitric oxide contributes to the analgesic action of intrathecal neostigmine in this rat model of diabetic neuropathic pain.
Cardiac and Neurologic Complications Identify Risks for Mortality for Both Men and Women Undergoing Coronary Artery Bypass Graft Surgery
Authors: Hogue Charles W. , Sundt Thoralf , Barzilai Benico , Schecthman Kenneth B. , Dávila-Román Victor G.
Published: November 2003

Background

Despite a number of studies showing that women and men respond to coronary artery bypass graft surgery differently, it is not known whether variables associated with mortality are the same for women and men. The purpose of this study was to identify variables independently associated with mortality for women undergoing coronary artery bypass graft surgery.

Methods

Single-institutional data were prospectively collected from 5,113 patients (1,558 or 30.5% women) undergoing coronary artery bypass graft surgery. The database was reviewed for patient characteristics and operative outcomes based on sex. Complications evaluated included low cardiac output syndrome (cardiac index < 2.0 l x min(-1) x m(-2) for > 8 h, regardless of treatment), stroke (new permanent global or focal motor deficits), Q-wave myocardial infarction, postoperative atrial fibrillation, and operative mortality.

Results

Women were older than men, and they were more likely to have preexisting hypertension, diabetes, and a history of stroke. Operative mortality for women was higher than for men (3.5% vs. 2.5%, P < 0.05). Compared with men, women were more likely to experience a postoperative myocardial infarction, stroke, and low cardiac output syndrome. When performing analysis on data from both sexes separately, low cardiac output syndrome, new stroke, myocardial infarction, and duration of cardiopulmonary bypass were independently associated with mortality for women and men both. Patient age was not independently associated with risk for mortality for women, but it was for men. However, when the authors combined both sexes in the logistic regression analysis, the age-sex interaction was not significant (P = 0.266), indicating that there was insufficient evidence to assert that age has a different effect on mortality for men and women.

Conclusions

These data confirm that women have higher perioperative mortality after coronary artery bypass graft surgery compared with men. A higher frequency of cardiac and neurologic complications seem to account to a large extent for the higher operative mortality for women. Factors independently associated with perioperative mortality are generally similar for women and men.
Intracuff Pressure and Tracheal Morbidity
Authors: Combes Xavier , Schauvliege Franck , Peyrouset Olivier , Motamed Cyrus , Kirov Kracen , Dhonneur Gilles , Duvaldestin Philippe
Published: November 2003

Background

Diffusion of nitrous oxide into the cuff of the endotracheal tube results in an increase in cuff pressure. Excessive endotracheal tube cuff pressure may impair tracheal mucosal perfusion and cause tracheal damage and sore throat. Filling the cuff of the endotracheal tube with saline instead of air prevents the increase in cuff pressure due to nitrous oxide diffusion. This method was used to test whether tracheal morbidity is related to excess in tracheal cuff pressure during balanced anesthesia.

Methods

Fifty patients with American Society of Anesthesiologists physical status I or II were randomly allocated to two groups with endotracheal tube cuffs initially inflated to 20-30 cm H(2)O with either air (group A) or saline (group S). Anesthesia was maintained with isoflurane and nitrous oxide. At the time of extubation, a fiberoptic examination of the trachea was performed by an independent observer, and abnormalities of tracheal mucosa at the level of the cuff contact area were scored. Patients assessed their symptoms (sore throat, dysphagia, and hoarseness) at the time of discharge from the postanesthesia care unit and 24 h after extubation on a 101-point numerical rating scale.

Results

Cuff pressure increased gradually during anesthesia in group A but remained stable in group S. The incidence of sore throat was greater in group A than in group S in the postanesthesia care unit (76 vs. 20%) and 24 h after extubation (42 vs. 12%; P < 0.05). Tracheal lesions at time of extubation were seen in all patients of group A and in eight patients (32%) of group S (P < 0.05).

Conclusion

Excess in endotracheal tube cuff pressure during balanced anesthesia due to nitrous oxide diffusion into this closed gas space causes sore throat that is related to tracheal mucosal erosion.
Inhaled Furosemide Inhibits Behavioral Response to Airway Occlusion in Anesthetized Cats
Authors: Nehashi Shino , Nishino Takashi , Ide Tohru
Published: November 2003

Background

A recent study showed that inhaled furosemide greatly improves experimentally induced dyspnea in humans. The objective of the current study is to test the hypothesis that inhaled furosemide suppresses the behavioral response to airway occlusion without changing the behavioral response to a somatic noxious stimulus in anesthetized animals.

Methods

In 10 spontaneously breathing cats anesthetized with isoflurane, anesthetic ED(50) was determined by measuring an end-tidal anesthetic concentration while observing escape behavior. The monitored behavior consisted of purposeful movement of the head and forearm after endotracheal tube occlusion. The duration from the start of airway occlusion to the onset of the positive response (DOCCL) was measured at the highest concentration of isoflurane permitting the positive motor response to airway occlusion before pretreatment. ED(50) values (minimum alveolar concentration) for the suppression of a somatic motor response to a noxious stimulus induced by toe pinch (toe-pinch ED(50)) were also determined. Then, the effects of inhaled furosemide or vehicle on the ED(50) for the suppression of the behavioral response to airway occlusion, DOCCL, and toe-pinch ED(50) were evaluated in a randomized, cross-over design.

Results

The ED(50) for the suppression of the behavioral response to airway occlusion significantly decreased (P < 0.01) and DOCCL was significantly prolonged (P < 0.01) after furosemide inhalation, whereas vehicle inhalation did not change these measurements. The decrease in ED(50) for the suppression of the behavioral response to airway occlusion after furosemide inhalation lasted 3 h. Furosemide inhalation did not affect the toe-pinch ED(50).

Conclusion

Inhaled furosemide suppressed the behavioral response to airway occlusion in anesthetized animals without affecting the response to somatic noxious stimulus. The authors' animal model of respiratory distress may be applicable to the study of dyspnea in regard to its mechanism and treatment.
Assessing Pediatric Anesthesia Practices for Volunteer Medical Services Abroad
Authors: Fisher Quentin A. , Nichols David , Stewart Frank C. , Finley G. Allen , Magee William P. , Nelson Kristi
Published: November 2003

Background

Anesthetic techniques and problems in volunteer medical services abroad are different from those of either the developed countries from which volunteers originate or the host country in which they serve because of differences in patient population, facilities, and goals for elective surgery. Assessing outcomes is hampered by the transience of medical teams and the global dispersion of providers. We studied general anesthesia techniques and outcomes in a large international voluntary surgical program.

Methods

Anesthesia providers and nurses participating in care of patients undergoing reconstructive plastic and orthopedic surgery by Operation Smile over an 18-month period were asked to complete a quality assurance data record for each case. Incomplete data were supplemented by reviewing the original patient records.

Results

General anesthesia was used in 87.1% of the 6,037 cases reviewed. The median age was 5 yr (25th-75th percentiles: 2-9 yr). Orofacial clefts accounted for more than 80% of procedures. Halothane mask induction was performed in 85.6% of patients; 96.3% of patients had tracheal intubation, which was facilitated with a muscle relaxant in 19.3%. Respiratory complications occurred during anesthesia in 5.0% of patients and during recovery (postanesthesia care unit) in 3.3%. Arrhythmias requiring therapy occurred in 1.5%, including three patients to whom cardiopulmonary resuscitation was administered. Prolonged ventilatory support was required in seven patients. There was one death. Inadvertent extubation during surgery occurred in 38 patients. Cancellation of surgery after induction of anesthesia occurred in 25 patients. Overall, complications were more common in younger children.

Conclusions

Our study showed that in this setting it is feasible to track anesthesia practice patterns and adverse perioperative events. We identified issues for further examination.
Spinal Ropivacaine for Cesarean Section
Authors: Khaw Kim S. , Ngan Kee Warwick D. , Wong Eliza L. Y. , Liu Justina Y. W. , Chung Raymond
Published: November 2003

Background

The dose-response relation for spinal ropivacaine is undetermined, and there are few data available for obstetric patients.

Methods

In a prospective, randomized, double-blind investigation, the authors studied 72 patients undergoing elective cesarean delivery. An epidural catheter was placed at the L2-L3 vertebral interspace. Lumbar puncture was then performed at the L3-L4 vertebral interspace, and patients were randomized to receive a dose of spinal ropivacaine diluted to 3 ml with normal saline: 10 mg (n = 12), 15 mg (n = 20), 20 mg (n = 20), or 25 mg (n = 20). Sensory changes assessed by ice and pin prick and motor changes assessed by modified Bromage score were recorded at timed intervals. A dose was considered effective if an upper sensory level to pin prick of T7 or above was achieved and epidural supplementation was not required intraoperatively.

Results

Anesthesia was successful in 8.3, 45, 70, and 90% of the 10-, 15-, 20-, and 25-mg groups, respectively. A sigmoid dose-response curve and a probit log dose-response plot were obtained, and the authors determined the ED50 (95% confidence interval) to be 16.7 (14.1-18.8) mg and the ED95 (95% confidence interval) to be 26.8 (23.6-34.1) mg. Duration of sensory and motor block and degree of motor block, but not onset of anesthesia, were positively related to dose.

Conclusions

The ED50 and estimated ED95 for spinal ropivacaine were 16.7 and 26.8 mg, respectively. Ropivacaine is a suitable agent for spinal anesthesia for cesarean delivery.
Morphine-induced Spinal Release of Adenosine Is Reduced in Neuropathic Rats
Authors: Sandner-Kiesling Andreas , Li Xinhui , Eisenach James C.
Published: November 2003

Background

Spinally administered opioids show decreased potency and efficacy in the treatment of neuropathic pain. As reported previously, morphine stimulates spinal opioid receptors to effect adenosine release, which acts at adenosine receptors to produce analgesia. The authors hypothesized that morphine induces less adenosine release in neuropathic compared with normal rats, explaining its reduced potency and efficacy.

Methods

Sprague-Dawley rats (200-250 g) were divided into three groups: no surgery (n = 52), sham surgery (n = 20), or left L5 and L6 spinal nerve ligation (n = 64). Two weeks after surgery, mechanical hypersensitivity of the left hind paw was verified. For each experiment, a crude synaptosomal P2 suspension was prepared by homogenizing cervical and lumbar dorsal spinal cord halves from four rats, followed by differential centrifugation, and aliquots incubated with morphine sulfate from 10(-8) to 10(-4) m alone or in presence of 10(-5) m dipyridamole. Extrasynaptosomal concentrations of adenosine were analyzed by high-pressure liquid chromatography.

Results

Synaptosomal release of adenosine in the absence of morphine was similar between groups. Morphine produced a concentration-dependent adenosine release, which was less in synaptosomes from dorsal lumbar spinal cord in spinal nerve ligation compared with normal or sham animals. This reduction was removed by adding dipyridamole.

Conclusion

Morphine normally stimulates spinal release of adenosine, a potent antihypersensitivity compound. Because this effect of morphine is diminished in spinal nerve ligation animals, one explanation for decreased efficacy and potency of opioids in the treatment of neuropathic pain may be a dipyridamole-sensitive disruption in the opioid-adenosine link in the spinal cord.
Widespread Inhibition of Sodium Channel–dependent Glutamate Release from Isolated Nerve Terminals by Isoflurane and Propofol
Authors: Lingamaneni Ratnakumari , Birch Martin L. , Hemmings Hugh C.
Published: November 2003

Background

Controversy persists concerning the mechanisms and role of general anesthetic inhibition of glutamate release from nerve endings. To determine the generality of this effect and to control for methodologic differences between previous studies, the authors analyzed the presynaptic effects of isoflurane and propofol on glutamate release from nerve terminals isolated from several species and brain regions.

Methods

Synaptosomes were prepared from rat, mouse, or guinea pig cerebral cortex and also from rat striatum and hippocampus. Release of endogenous glutamate evoked by depolarization with 20 microm veratridine (which opens voltage-dependent Na+ channels by preventing inactivation) or by 30 mm KCl (which activates voltage-gated Ca2+ channels by membrane depolarization) was monitored using an on-line enzyme-linked fluorometric assay.

Results

Glutamate release evoked by depolarization with increased extracellular KCl was not significantly inhibited by isoflurane up to 0.7 mM ( approximately 2 minimum alveolar concentration; drug concentration for half-maximal inhibition [IC50] > 1.5 mM) [corrected] or propofol up to 40 microm in synaptosomes prepared from rat, mouse, or guinea pig cerebral cortex, rat hippocampus, or rat striatum. Lower concentrations of isoflurane or propofol significantly inhibited veratridine-evoked glutamate release in all three species (isoflurane IC50 = 0.41-0.50 mm; propofol IC50 = 11-18 microm) and rat brain regions. Glutamate release was evoked by veratridine or increased KCl (from 5 to 35 mM) to assess the involvement of presynaptic ion channels as targets for drug actions [corrected].

Conclusions

Isoflurane and propofol inhibited Na+ channel-mediated glutamate release evoked by veratridine with greater potency than release evoked by increased KCl in synaptosomes prepared from three mammalian species and three rat brain regions. These findings are consistent with a greater sensitivity to anesthetics of presynaptic Na+ channels than of Ca2+ channels coupled to glutamate release. This widespread presynaptic action of general anesthetics is not mediated by potentiation of gamma-aminobutyric acid type A receptors, though additional mechanisms may be involved.
Efficacy of Tactile-guided Reversal from Cisatracurium-induced Neuromuscular Block
Authors: Kirkegaard Hans , Heier Tom , Caldwell James E.
Published: November 2003

Background

Because tactile evaluation is the most common form of clinical neuromuscular monitoring, this study examines the relative efficacy of antagonizing residual block at different levels of recovery of the tactile train-of-four (TOF) response.

Methods

Anesthesia was induced in 64 adults with 2-5 microg/kg fentanyl and 1-3 mg/kg propofol and maintained with fentanyl, propofol, and nitrous oxide. The tactile response of the adductor pollicis to TOF stimulation was evaluated at one arm, and the mechanomyographic response was recorded at the other. Patients received 0.15 mg/kg cisatracurium and were randomized to receive 0.07 mg/kg neostigmine on reappearance of the first (group I), second (group II), third (group III), or fourth (group IV) tactile TOF response (16 patients per group). Times from administration of neostigmine until the TOF ratio recovered to 0.7 (R0.7), 0.8 (R0.8), and 0.9 (R0.9) were measured.

Results

Data are presented as median with range in parentheses. R0.7 was 10.3 (5.9-23.4), 7.6 (3.2-14.1), 5.0 (2.0-18.4), and 4.1 (2.4-11.0) min in groups I, II, III, and IV, respectively (P < 0.05, group I > II, III, and IV, group II > IV). R0.8 was 16.6 (8.9-30.7), 9.8 (5.3-25.0), 8.3 (3.8-27.1), and 7.5 (3.0-74.5) min in groups I, II, III, and IV, respectively (P < 0.05, group I > II, III, and IV, group II > IV). R0.9 was 22.2 (13.9-44.0), 20.2 (6.5-70.5), 17.1 (8.3-46.2), and 16.5 (6.5-143.3) min in groups I, II, III, and IV, respectively (no intergroup differences). Ten minutes after neostigmine, a TOF ratio of 0.7 or greater was achieved in 50, 75, 88, and 93% of patients in groups I, II, III, and IV, respectively (P < 0.05 group I > II, III, and IV). At 30 min, a TOF ratio of 0.9 or less was observed in 21, 13, 13, and 7% of patients in groups I, II, III, and IV respectively (no intergroup differences).

Conclusions

To achieve rapid (within 10 min) reversal to a TOF ratio of 0.7 in more than 87% of patients, three or four tactile responses should be present at the time of neostigmine administration. It was not possible within 30 min to achieve a TOF ratio of 0.9 in all patients, regardless of the number of tactile responses present at neostigmine administration.