bluuebunny/crossref_metadata_2025 huggingface dataset:
The Antiallodynic Effects of Intrathecal Cholinesterase Inhibitors in a Rat Model of Neuropathic Pain
Authors: Hwang Jai-Hyun , Hwang Kyu-Sam , Leem Jeong-Kil , Park Pyung-Hwan , Han Sung-Min , Lee Dong-Myung
Published: November 2003

Background

This study determined the effect of intrathecally administered cholinesterase inhibitors, edrophonium and neostigmine, on nerve injury-induced, touch-evoked allodynia and identified the pharmacologic characteristics of this action.

Methods

Rats were prepared with tight ligation of the left L5 and L6 spinal nerves and with lumbar intrathecal catheters fitted for long-term monitoring. Edrophonium (3, 10, 30, or 100 microg) or neostigmine (0.3, 1, 3, or 10 microg) was administered intrathecally. Tactile allodynia and motor weakness were assessed. To evaluate the pharmacologic characteristics of the activity, a muscarinic receptor antagonist or a nicotinic receptor antagonist was administered intrathecally before edrophonium or neostigmine was injected. To compare the action of subtype antagonists, the M1 muscarinic receptor antagonist pirenzepine, the M2 antagonist methoctramine, the M3 antagonist 4-DAMP (diphenylacetoxy-N-methypiperidine), and the M4 antagonist tropicamide were administered intrathecally before cholinesterase inhibitors were injected.

Results

Intrathecal edrophonium or neostigmine produced a dose-dependent antagonism of the touch-evoked allodynia. Neostigmine resulted in a moderate effect on motor weakness at doses of 3 and 10 microg. Pretreatment with intrathecal atropine but not mecamylamine yielded a complete antagonism of the effects of the cholinesterase inhibitors. In addition, antiallodynia produced by edrophonium (100 microg) was reversed by pretreatment with methoctramine, 4-DAMP, tropicamide, and pirenzepine. In the neostigmine (10 microg) group, only the M1 antagonist pirenzepine had a moderate effect on reversal of increased allodynic threshold.

Conclusions

These experiments suggest that intrathecal edrophonium or neostigmine produces an antagonism on touch-evoked allodynia at the spinal level in a rat model of neuropathic pain and that the antiallodynic action of cholinesterase inhibitors is probably mediated by a spinal muscarinic system, especially at the M1 receptor subtype.
Spinal Antinociceptive Action of Na+-K +Pump Inhibitor Ouabain and Its Interaction with Morphine and Lidocaine in Rats
Authors: Zeng Weian , Dohi Shuji , Shimonaka Hiroyuki , Asano Toshio
Published: November 2003

Background

The Na+,K+-adenosine triphosphatase is a ubiquitous enzyme system that maintains the ion gradient across the plasma membrane of a variety of cell types, including cells in the central nervous system. We investigated the antinociceptive effect of intrathecally administered ouabain and examined its potential interaction with spinal morphine and lidocaine.

Methods

Using rats chronically implanted with lumbar intrathecal catheters, the ability of intrathecally administered ouabain, morphine, and lidocaine and of mixtures of ouabain-morphine and ouabain-lidocaine to alter tail-flick latency was examined. To characterize any interactions, isobolographic analysis was performed. The effects of pretreatment with intrathecally administered atropine or naloxone also were tested.

Results

Intrathecally administered ouabain (0.1-5.0 microg), morphine (0.2-10.0 microg), and lidocaine (25-300 microg) given alone produced significant dose- and time-dependent antinociception, but systemic administration of ouabain did not produce such an effect. The median effective dose (ED50) values for intrathecally administered ouabain, morphine, and lidocaine were 2.3, 5.0, and 227.0 microg, respectively. Isobolographic analysis exhibited a synergistic interaction after the coadministration of ouabain and morphine. With ouabain and lidocaine, there was no such evidence of synergism. Intrathecally administered atropine, but not naloxone, completely blocked the antinociceptive effect of ouabain and attenuated its interaction with spinally administered morphine.

Conclusions

Intrathecally administered ouabain produces antinociception, at least in part, via an enhancement of cholinergic transmission in the spinal nociceptive processing system. The results of the interaction of ouabain with morphine and lidocaine suggest that modulation of Na+-,K+-electrochemical gradients and thus subsequent release of neurotransmitters in the spinal cord are likely to play important roles in the spinal antinociceptive effect of intrathecally administered ouabain.
Dependence of Explicit and Implicit Memory on Hypnotic State in Trauma Patients
Authors: Lubke Gitta H. , Kerssens Chantal , Phaf Hans , Sebel Peter S.
Published: November 2003

Background

It is still unclear whether memory of intraoperative events results entirely from moments of inadequate anesthesia. The current study was designed to determine whether the probability of memory declines with increasing depth of the hypnotic state.

Method

A list of words was played via headphones during surgery to patients who had suffered acute trauma. Several commonly used indicators of anesthetic effect, including the bispectral index, were recorded during word presentation. First, these indicators served as predictors of the memory performance in a postoperative word stem completion test. Second, general memory performance observed in the first part was separated into explicit and implicit memory using the process dissociation procedure, and then two models of memory were compared: One model assumed that the probability of explicit and implicit memory decreases with increasing depth of hypnotic state (individual differences model), whereas the other assumed equal memory performance for all patients regardless of their level of hypnotic state.

Results

General memory performance declined with decreasing bispectral index values. None of the other indicators of hypnotic state were related to general memory performance. Memory was still significant at bispectral index levels between 60 and 40. A comparison of the two models of memory resulted in a better fit of the individual differences model, thus providing evidence of a dependence of explicit and implicit memory on the hypnotic state. Quantification of explicit and implicit memory revealed a significant implicit but no reliable explicit memory performance.

Conclusions

This study clearly indicates that memory is related to the depth of hypnosis. The observed memory performance should be interpreted in terms of implicit memory. Auditory information processing occurred at bispectral index levels between 60 and 40.
Cardiac Baroreflex during the Postoperative Period in Patients with Hypertension
Authors: Parlow Joel L. , Begou Gerard , Sagnard Pierre , Cottet-Emard Jean Marie , Levron Jean Claude , Annat Guy , Bonnet Francis , Ghignone Marco , Hughson Richard , Viale Jean-Paul , Quintin Luc
Published: November 2003

Background

Patients with essential hypertension show altered baroreflex control of heart rate, and during the perioperative period they demonstrate increased circulatory instability. Clonidine has been shown to reduce perioperative circulatory instability. This study documents changes in measures of heart rate control after surgery in patients with essential hypertension and determines the effects of clonidine on postoperative heart rate control in these patients.

Methods

Using a randomized double-blind placebo-controlled design, 20 patients with essential hypertension (systolic pressure >160 mm Hg or diastolic pressure >95 mm Hg for > or =1 yr) were assigned to receive clonidine (or placebo), 6 microg/kg orally 120 min before anesthesia and 3 microg/kg intravenously over 60 min before the end of surgery. The spontaneous baroreflex ("sequence") technique and analysis of heart rate variability were used to quantify control of heart rate at baseline, before induction of anesthesia, and 1 and 3 h postoperatively.

Results

Baroreflex slope and heart rate variability were reduced postoperatively in patients given placebo but not those given clonidine. Clonidine resulted in greater postoperative baroreflex slope and power at all frequency ranges compared with placebo (4.9+/-2.9 vs. 2.2+/-2.1 ms/mm Hg for baroreflex slope, 354+/-685 vs. 30+/-37 ms2/Hz for high frequency variability). Clonidine also resulted in lower concentrations of catecholamine, decreased mean heart rate and blood pressure, and decreased perioperative tachycardia and hypertension.

Conclusions

Patients with hypertension exhibit reduced heart rate control during the recovery period after elective surgery. Clonidine prevents this reduction in heart rate control. This may represent a basis for the improved circulatory stability seen with perioperative administration of clonidine.
Functional Brain Imaging during Anesthesia in Humans
Authors: Alkire Michael T. , Pomfrett Chris J. D. , Haier Richard J. , Gianzero Marc V. , Chan Candice M. , Jacobsen Bradley P. , Fallon James H.
Published: November 2003

Background

Propofol and isoflurane anesthesia were studied previously with functional brain imaging in humans to begin identifying key brain areas involved with mediating anesthetic-induced unconsciousness. The authors describe an additional positron emission tomography study of halothane's in vivo cerebral metabolic effects.

Methods

Five male volunteers each underwent two positron emission tomography scans. One scan assessed awake-baseline metabolism, and the other scan assessed metabolism during halothane anesthesia titrated to the point of unresponsiveness (mean +/- SD, expired = 0.7+/-0.2%). Scans were obtained using a GE2048 scanner and the F-18 fluorodeoxyglucose technique. Regions of interest were analyzed for changes in both absolute and relative glucose metabolism. In addition, relative changes in metabolism were evaluated using statistical parametric mapping.

Results

Awake whole-brain metabolism averaged 6.3+/-1.2 mg x 100 g(-1) x min(-1) (mean +/- SD). Halothane reduced metabolism 40+/-9% to 3.7+/-0.6 mg x 100 g(-1) x min(-1) (P< or =0.005). Regional metabolism did not increase in any brain areas for any volunteer. The statistical parametric mapping analysis revealed significantly less relative metabolism in the basal forebrain, thalamus, limbic system, cerebellum, and occiput during halothane anesthesia.

Conclusions

Halothane caused a global whole-brain metabolic reduction with significant shifts in regional metabolism. Comparisons with previous studies reveal similar absolute and relative metabolic effects for halothane and isoflurane. Propofol, however, was associated with larger absolute metabolic reductions, suppression of relative cortical metabolism more than either inhalational agent, and significantly less suppression of relative basal ganglia and midbrain metabolism.
Postoperative Behavioral Outcomes in Children
Authors: Kain Zeev N. , Mayes Linda C. , Wang Shu-Ming , Hofstadter Maura B.
Published: November 2003

Background

Although multiple studies document the effect of sedative premedication on preoperative anxiety in children, there is a paucity of data regarding its effect on postoperative behavioral outcomes.

Methods

After screening for recent stressful life events, children undergoing anesthesia and surgery were assigned randomly to receive either 0.5 mg/kg midazolam in 15 mg/kg acetaminophen orally (n = 43) or 15 mg/kg acetaminophen orally (n = 43). Using validated measures of anxiety, children were evaluated before and after administration of the intervention and during induction of anesthesia. On postoperative days 1, 2, 3, 7, and 14, the behavioral recovery of the children was assessed using the Post Hospitalization Behavior Questionnaire.

Results

The intervention group demonstrated significantly lower anxiety levels compared with the placebo group on separation to the operating room and during induction of anesthesia (F[1,77] = 3.95, P = 0.041). Using a multivariate logistic regression model, the authors found that the presence or absence of postoperative behavioral changes was dependent on the group assignment (R = 0.18, P = 0.0001) and days after operation (R = -0.20, P = 0.0001). Post hoc analysis demonstrated that during postoperative days 1-7, a significantly smaller number of children in the midazolam group manifested negative behavioral changes. At week 2 postoperatively, however, there were no significant differences between the midazolam and placebo groups.

Conclusions

Children who are premedicated with midazolam before surgery have fewer negative behavioral changes during the first postoperative week.
Potassium Channel-mediated Hyperpolarization of Mesenteric Vascular Smooth Muscle by Isoflurane
Authors: Kokita Naohiro , Stekiel Thomas A. , Yamazaki Mitsuaki , Bosnjak Zeljko J. , Kampine John P. , Stekiel William J.
Published: November 2003

Background

A primary source of calcium (Ca2+) necessary for excitation contraction in vascular smooth muscle (VSM) is influx via voltage-dependent Ca2+ channels. Thus, force generation in VSM is coupled closely to resting transmembrane potential, which itself is primarily a function of potassium conductance. Previously, the authors reported that volatile anesthetics hyperpolarize VSM of small mesenteric resistance arteries and capacitance veins. The current study was designed to determine whether isoflurane-mediated hyperpolarization is the result of specific effects on one or more of four types of potassium channels known to exist in VSM.

Methods

Transmembrane potentials (Em) were recorded from in situ mesenteric capacitance and resistance vessels in Sprague-Dawley rats weighing 250-300 g. In separate experiments, selective inhibitors of each of four types of potassium channels known to exist in VSM were administered in the superfusate of the vessel preparations to assess their effects on isoflurane-mediated hyperpolarization.

Results

Resting VSM Em ranged from -38 to -43 mV after local sympathetic denervation. Isoflurane produced a significant hyperpolarization (2.7-4.3 mV), whereas each potassium channel inhibitor significantly depolarized (2.8-8.5 mV) the VSM. Both 100 nM iberiotoxin (inhibitor of high conductance calcium-activated potassium channels) and 1 microM glybenclamide (inhibitor of adenosine triphosphatase-sensitive potassium channels) significantly inhibited VSM hyperpolarization induced by 1 MAC (minimum alveolar concentration) levels of inhaled isoflurane (0.1-0.9 mV Em change, which was not significant). In contrast, isoflurane hyperpolarized the VSM significantly despite the presence of 3 mM 4 aminopyridine (inhibitor of voltage-dependent potassium channels) or 10 microM barium chloride (an inhibitor of inward rectifier potassium channels) (3.7-8.2 mV change in VSM Em).

Conclusions

These results suggest that isoflurane-mediated hyperpolarization (and associated relaxation) of VSM can be attributed in part to an enhanced (or maintained) opening of calcium-activated and adenosine triphosphate-sensitive potassium channels but not voltage-dependent or inward rectifier potassium channels.
Mechanisms of Isoflurane-induced Myocardial Preconditioning in Rabbits
Authors: Ismaeil Mohamed S. , Tkachenko Igor , Gamperl Kurt A. , Hickey Robert F. , Cason Brian A.
Published: November 2003

Background

Isoflurane has cardioprotective effects that mimic the ischemic preconditioning phenomenon. Because adenosine triphosphate-sensitive potassium channels and adenosine receptors are implicated in ischemic preconditioning, the authors wanted to determine whether the preconditioning effect of isoflurane is mediated through these pathways.

Methods

Myocardial infarct size was measured in seven groups of propofol-anesthetized rabbits, each subjected to 30 min of anterolateral coronary occlusion followed by 3 h of reperfusion. Groups differed only in the pretreatments given, and controls received no pretreatment. An ischemia-preconditioned group was pretreated with 5 min of coronary occlusion and 15 min of reperfusion. An isoflurane-preconditioned group was pretreated with 15 min end-tidal isoflurane, 1.1%, and then 15 min of washout. An isoflurane-plus-glyburide group was administered 0.33 mg/kg glyburide intravenously before isoflurane pretreatment. An isoflurane plus 8-(p-sulfophenyl)-theophylline (SPT) group received 7.5 mg/kg SPT intravenously before isoflurane. Additional groups were administered identical doses of glyburide or SPT, but they were not pretreated with isoflurane. Infarct size and area at risk were defined by staining. Data were analyzed by analysis of variance or covariance.

Results

Infarct size, expressed as a percentage of the area at risk (IS:AR) was 30.2+/-11% (SD) in controls. Ischemic preconditioning and isoflurane preexposure reduced myocardial infarct size significantly, to 8.3+/-5% and 13.4+/-8.2% (P<0.05), respectively. Both glyburide and SPT pretreatment eliminated the preconditioning-like effect of isoflurane (IS:AR = 30.0+/-9.1% and 29.2+/-12.6%, respectively; P = not significant). Neither glyburide nor SPF alone increased infarct size (IS:AR = 33.9+/-7.6% and 31.8+/-12.7%, respectively; P = not significant).

Conclusions

Glyburide and SPT abolished the preconditioning-like effects of isoflurane but did not increase infarct size when administered in the absence of isoflurane. Isoflurane-induced preconditioning and ischemia-induced preconditioning share similar mechanisms, which include activation of adenosine triphosphate-sensitive potassium channels and adenosine receptors.
Lamotrigine Attenuates Cortical Glutamate Release during Global Cerebral Ischemia in Pigs on Cardiopulmonary Bypass
Authors: Conroy Brendan P. , Black Damon , Lin Cheng Y. , Jenkins Larry W. , Crumrine Christian R. , DeWitt Douglas S. , Johnston William E.
Published: November 2003

Background

The dose-response effects of pretreatment with lamotrigine (a phenyltriazine derivative that inhibits neuronal glutamate release) in a porcine cerebral ischemia model during cardiopulmonary bypass were studied.

Methods

Sagittal sinus catheters and cortical microdialysis catheters were inserted into anesthetized pigs. Animals undergoing normothermic cardiopulmonary bypass were pretreated with lamotrigine 0, 10, 25, or 50 mg/kg (n = 10 per group). Fifteen minutes of global cerebral ischemia was produced, followed by 40 min of reperfusion and discontinuation of cardiopulmonary bypass. Cerebral oxygen metabolism was calculated using cerebral blood flow (radioactive microspheres) and arterial-venous oxygen content gradients. Concentrations of microdialysate glutamate and aspartate were quantified; electroencephalographic signals were recorded. After cardiopulmonary bypass, blood and cerebrospinal fluid were sampled for S-100B protein, and a biopsy was performed on the cerebral cortex for metabolic profile.

Results

Lamotrigine caused dose-dependent reductions in systemic vascular resistance so that additional fluid was required to maintain venous return. Concentrations of glutamate and aspartate did not change during reperfusion after 50 mg/kg lamotrigine in contrast to fivefold and twofold increases, respectively, with lower doses. There were no intergroup differences in cerebral metabolism, electroencephalographic scores, cortical metabolites, brain lactate, or S-100B protein concentrations in the cerebrospinal fluid and blood.

Conclusions

Lamotrigine 50 mg/kg significantly attenuated excitatory neurotransmitter release during normothermic cerebral ischemia during cardiopulmonary bypass without improving other neurologic parameters. Lamotrigine caused arterial and venous dilation, which limits its clinical usefulness.
Effects of an Intubating Dose of Succinylcholine and Rocuronium on the Larynx and Diaphragm
Authors: Dhonneur Gilles , Kirov Krassen , Slavov Velislav , Duvaldestin Philippe
Published: November 2003

Background

Paralysis of the vocal cords is one objective of using relaxants to facilitate tracheal intubation. This study compares the neuromuscular blocking effect of succinylcholine and rocuronium on the larynx, the diaphragm, and the adductor pollicis muscle.

Methods

Electromyographic response was used to compare the neuromuscular blocking effect of succinylcholine and rocuronium on the laryngeal adductor muscles, the diaphragm, and the adductor pollicis muscle. Sixteen patients undergoing elective surgery were anesthetized with propofol and fentanyl, and their tracheas were intubated without neuromuscular blocking agents. The recurrent laryngeal and phrenic nerves were stimulated at the neck. The electromyographic response was recorded from electrodes placed on the endotracheal tube and intercostally before and after administration of 1 mg/kg succinylcholine or 0.6 mg/kg rocuronium.

Results

The maximum effect was greater at the adductor pollicis (100 and 99%) than at the larynx (96 and 97%) and the diaphragm (94 and 96%) after administration of succinylcholine and rocuronium, respectively (P < or = 0.05). Onset time was not different between the larynx (58+/-10 s), the diaphragm (57+/-8 s), and the adductor pollicis (54+/-13 s), after succinylcholine (all mean +/- SD). After rocuronium, onset time was 124+/-39 s at the larynx, 130+/-44 s at the diaphragm, and 115+/-21 s at the adductor pollicis. After succinylcholine administration, time to 90% recovery was 8.3+/-3.2, 7.2+/-3.5, and 9.1+/-3.0 min at the larynx, the diaphragm, and the adductor pollicis, respectively. Time to 90% recovery after rocuronium administration was 34.9+/-7.6, 30.4+/-4.2, and 49.1+/-11.4 min at the larynx, the diaphragm, and the adductor pollicis, respectively.

Conclusion

Neuromuscular blocking effect of muscle relaxants on the larynx can be measured noninvasively by electromyography. Although the larynx appears to be resistant to muscle relaxants, we could not demonstrate that its onset time differed from that of peripheral muscles.
Effects of Prophylactic Nalmefene on the Incidence of Morphine-related Side Effects in Patients Receiving Intravenous Patient-controlled Analgesia
Authors: Joshi Girish P. , Duffy Larry , Chehade Jamal , Wesevich Jay , Gajraj Noor , Johnson Edward R.
Published: November 2003

Background

Opioid-related side effects associated with intravenous patient-controlled analgesia can be reduced by a low-dose naloxone infusion. The influence of nalmefene, a pure opioid antagonist with a longer duration of action, on opioid-related side effects has not been evaluated. This study was designed to determine the dose-response relation for nalmefene for the prevention of morphine-related side effects in patients receiving intravenous patient-controlled analgesia.

Methods

One hundred twenty women undergoing lower abdominal surgery were enrolled in the study. General anesthesia was induced using thiopental and rocuronium and maintained with desflurane, nitrous oxide, and fentanyl or sufentanil. All patients received neostigmine and glycopyrrolate to reverse residual neuromuscular blockade. No prophylactic antiemetics were administered. At the end of surgery, patients were randomized to receive saline, 15 microg nalmefene, or 25 microg nalmefene intravenously. The need for antiemetic and antipruritic drugs and the total consumption of morphine during the 24-h study were recorded. The incidences of postoperative nausea, vomiting, pruritus, and pain were recorded 30 min after patients were admitted to the postanesthesia care unit. In addition, patient remembrance of these side effects was noted at 24 h after operation.

Results

The need for antiemetic and antipruritic medications during the 24-h study period was significantly lower in the patients receiving nahmefene compared with those receiving placebo. However, the need to treat side effects was similar in the two nahmefene groups. Prophylactic administration of nalmefene reduced the patients remembrance of nausea and itching as assessed 24 h after operation. Although the total consumption of morphine during the 24-h study period was similar in the three groups, retrospectively patients who received nalmefene characterized their pain as less severe in the previous 24 h.

Conclusion

Compared with placebo, prophylactic administration of nalmefene significantly decreased the need for antiemetics and antipruritic medications in patients receiving intravenous patient-controlled analgesia with morphine.
Halothane Induces Calcium Release from Human Skinned Masseter Muscle Fibers
Authors: Reyford Hugo , Adnet Pascal J. , Tavernier Benoit , Beague Sebastien , Ferri Joel , Krivosic-Horber Renee M. , Haudecoeur Ghislain
Published: November 2003

Background

An increase in masseter muscle tone in response to halothane or succinylcholine anesthesia (or both) can be observed in healthy persons. Thus the authors compared the fiber-type halothane and succinylcholine sensitivities in human masseter and vastus lateralis muscles.

Methods

Masseter and vastus lateralis muscle segments were obtained from 13 and 9 healthy persons, respectively. After chemical skinning of a single fiber and loading the sarcoplasmic reticulum with Ca++ 0.16 microM solution, halothane (0.5-4 vol% bubbled in the incubating solution), succinylcholine (0.1 microM to 10 mM), or both sensitivities were defined as the concentration inducing more than 10% of the maximum tension obtained by application of 16 microM Ca++ solution. The myofilament response to Ca++ was studied with and without halothane by observing the isometric tension of skinned masseter fibers challenged with increasing concentrations of Ca++. Muscle fiber type was determined by the difference in strontium-induced tension measurements.

Results

A significant difference in halothane sensitivity was found between type 1 masseter fibers (0.6+/-0.2 vol%; mean +/- SD) versus type 1 (2.7+/-0.6 vol%) and type 2 vastus lateralis muscle (2.5+/-0.4 vol%). Succinylcholine did not induce Ca++ release by the sarcoplasmic reticulum. In the masseter muscle, 0.75 vol% halothane decreased the maximal activated tension by 40% but did not change the Ca++ concentration that yields 50% of the maximal tension.

Conclusions

The very low halothane threshold for Ca++ release from the masseter muscle usually could be counteracted by a direct negative inotropic effect on contractile proteins. However, halothane may increase the sensitivity of the sarcoplasmic reticulum Ca++ release to succinylcholine-induced depolarization, leading to an increase in masseter muscle tone.
Awareness during Anesthesia
Authors: Domino Karen B. , Posner Karen L. , Caplan Robert A. , Cheney Frederick W.
Published: November 2003

Background

Awareness during general anesthesia is a frightening experience, which may result in serious emotional injury and post-traumatic stress disorder. We performed an in-depth analysis of cases from the database of the American Society of Anesthesiologists Closed Claims Project to explore the contribution of intraoperative awareness to professional liability in anesthesia.

Methods

The database of the Closed Claims Project is composed of closed US malpractice claims that have been collected in a standardized manner. All claims for intraoperative awareness were reviewed by the reviewers to identify patterns of causation and standard of care. Logistic regression analysis was used to identify independent patient and anesthetic factors associated with claims for recall during general anesthesia compared to other general anesthesia malpractice claims.

Results

Awareness claims accounted for 79 (1.9%) of 4,183 claims in the database, including 18 claims for awake paralysis, i.e., the inadvertent paralysis of an awake patient, and 61 claims for recall during general anesthesia, ie., recall of events while receiving general anesthesia. The majority of awareness claims involved women (77%), younger than 60 yr of age (89%), American Society of Anesthesiologists physical class I-II (68%), who underwent elective surgery (87%). Most (94%) claims for awake paralysis represented substandard care involving errors in labeling and administration, whereas care was substandard in only 43% of the claims for recall during general anesthesia (P < 0.001). Claims for recall during general anesthesia were more likely to involve women (odds ratio [OR] = 3.08, 95% confidence interval [CI] = 1.58, 6.06) and anesthetic techniques using intraoperative opioids (OR = 2.12, 95% CI = 1.20, 3.74), intraoperative muscle relaxants (OR = 2.28, 95% CI = 1.22, 4.25), and no volatile anesthetic (OR = 3.20, 95% CI = 1.88, 5.46).

Conclusions

Deficiencies in labeling and vigilance were common causes for awake paralysis. Claims for recall during general anesthesia were more likely in women and with nitrous-narcotic-relaxant techniques.
Contribution of Peripheral Chemoreception to the Depression of the Hypoxic Ventilatory Response during Halothane Anesthesia in Cats
Authors: Ide Tohru , Sakurai Yasuyoshi , Aono Mitsuo , Nishino Takashi
Published: November 2003

Background

The effects of inhalational anesthetics on the hypoxic ventilatory response are complex. This study was designed to determine the contribution of peripheral chemoreception to the depression of hypoxic ventilatory response seen with halothane anesthesia.

Methods

Cats were anesthetized with pentobarbital sodium and alpha-chloralose and artificially ventilated. Respiratory output was evaluated by phasic inspiratory activity of the phrenic nerve. In 12 cats, this activity was measured during inhalation of an hypoxic gas mixture with halothane, 0, 0.1, and 0.8%, with intact or denervated carotid bodies. In 10 cats, a carotid body was isolated from the systemic circulation and perfused with hypoxic Krebs-Ringer solution equilibrated with halothane, 0, 0.1, and 0.8%.

Results

The hypoxic ventilatory response was depressed in a dose-dependent manner during halothane anesthesia. In carotid body perfusion studies, the response was significantly depressed only with halothane, 0.80%.

Conclusion

The hypoxic ventilatory response is depressed by a high dose of halothane through a peripheral effect at the carotid body.
Volatile Anesthetics Increase Intracellular Calcium in Cerebrocortical and Hippocampal Neurons
Authors: Kindler Christoph H. , Eilers Helge , Donohoe Paul , Ozer Surhan , Bickler Philip E.
Published: November 2003

Background

An increase in intracellular calcium concentration ([Ca2+]i) in neurons has been proposed as an important effect of volatile anesthetics, because they alter signaling pathways that influence neurotransmission. However, the existing data for anesthetic-induced increases in [Ca2+]i conflict.

Methods

Changes in [Ca2+]i were measured using fura-2 fluorescence spectroscopy in rat cortical brain slices at 90, 185, 370, and 705 microM isoflurane. To define the causes of an increase in [Ca2+]i, slices were studied in Ca2+-free medium, in the presence of Ca2+-channel blockers, and in the presence of the Ca2+-release inhibitor azumolene. The authors compared the effect of the volatile anesthetic with that of the nonanesthetic compound 1,2-dichlorohexafluorocyclobutane. Single-dose experiments in CA1 neurons in hippocampal slices with halothane (360 microM) and in acutely dissociated CA1 neurons with halothane (360 microM) and isoflurane (445 microM) also were performed.

Results

Isoflurane at 0.5, 1, and 2 minimum alveolar concentrations increased basal [Ca2+]i in cortical slices in a dose-dependent manner (P < 0.05). This increase was not altered by Ca2+-channel blockers or Ca2+-free medium but was reduced 85% by azumolene. The nonanesthetic 1,2-dichlorohexafluorocyclobutane did not increase [Ca2+]i. In dissociated CA1 neurons, isoflurane reversibly increased basal [Ca2+]i by 15 nM (P < 0.05). Halothane increased [Ca2+]i in dissociated CA1 neurons and CA1 neurons in hippocampal slices by approximately 30 nM (P < 0.05).

Conclusions

(1) Isoflurane and halothane reversibly increase [Ca2+]i in isolated neurons and in neurons within brain slices. (2) The increase in [Ca2+]i is caused primarily by release from intracellular stores. (3) Increases in [Ca2+]i occur with anesthetics but not with the nonanesthetic 1,2-dichlorohexafluorocyclobutane.
Acetazolamide and Amiloride Inhibit Pentobarbital-induced Facilitation of Nocifensive Reflexes
Authors: Archer David P. , Roth Sheldon
Published: November 2003

Background

Neuronal excitation may result from stimulation of gamma-aminobutyric acid A (GABA(A)) receptors that prolong the channel opening, depolarizing the postsynaptic membrane. Drugs such as acetazolamide or amiloride can block GABA depolarization. Barbiturates facilitate nociceptive reflexes and also prolong the GABA(A) channel open-time. To evaluate the possible mechanism, the authors studied the impact of acetazolamide and amiloride on pentobarbital-induced nocifensive reflex facilitation. Because nitric oxide (NO) is a mediator of reflex facilitation, the authors evaluated the effects of NO synthase inhibition.

Methods

Nocifensive reflex thresholds were quantified with the hind paw withdrawal latency from radiant heat (HPW latency) in the rat. Nocifensive reflexes were facilitated with intraperitoneal injection of pentobarbital (30 mg/kg). The authors tested the roles of GABA-mediated depolarization and NO in reflex facilitation by pretreatment with acetazolamide and amiloride and inhibition of NO synthase with L-NAME and 7-NI, respectively. Sedative effects of pentobarbital were evaluated with the righting reflex, the response to vibrissal stimulation, and plasma drug concentrations.

Results

Pentobarbital decreased the hind paw withdrawal latency from 11.2+/-1 to 8.3+/-1 s (P < 0.001). Pretreatment with each of the four test drugs limited the reduction in reflex facilitation after pentobarbital to 1.3 s or less, similar to the reduction seen after saline injection, without altering sedation. L-NAME increased plasma pentobarbital concentrations by 10% without changing the concentration associated with return of responsiveness.

Conclusions

Pentobarbital-induced nocifensive reflex facilitation was inhibited by all four tested drugs without evidence of increased sedation. The results are consistent with a role for GABA(A) receptor-mediated depolarization in barbiturate-induced hyper-reflexia.
Individualized Feedback of Volatile Agent Use Reduces Fresh Gas Flow Rate, but Fails to Favorably Affect Agent Choice
Authors: Body Simon C. , Fanikos John , DePeiro David , Philip James H. , Segal Scott B.
Published: November 2003

Background

Cost reduction has become an important fiscal aim of many hospitals and anesthetic departments, despite its inherent limitations. Volatile anesthetic agents are some of the few drugs that are amenable to such treatment because fresh gas flow rate (FGFR) can be independent of patient volatile anesthetic agent requirement.

Methods

FGFR and drug use were recorded at the temporal midpoint of 2,031 general anesthetics during a 2-month preintervention period. Staff and residents were provided with their preintervention individual mean FGFR, their peer group mean, and educational material regarding volatile agent costs and low-flow anesthesia. FGFR and drug use were remeasured over a 2-month period (postintervention) immediately after this information (N = 2,242) and again 5 months later (delayed follow-up), for a further 2-month period (N = 2,056).

Results

For all cases, FGFR decreased from 2.4+/-1.1 to 1.8+/-1.0 l/min (26% reduction) after the intervention and increased to 1.9+/-1.1 l/min (5% increase of preintervention FGFR) at the time of delayed follow-up. Use of more expensive volatile agents (desflurane and sevoflurane) increased during the study period (P < 0.01). In a subgroup of 44 staff members with more than five cases in all study periods, 42 members decreased their mean FGFR after intervention. At delayed follow-up, 30 members had increased their FGFR above postintervention FGFR but below their initial FGFR. After accounting for other predictors of FGFR, the effectiveness of the intervention was significantly reduced at follow-up (28% reduction), but retained a significant effect compared to preintervention FGFR (19% reduction).

Conclusions

Although individual feedback and education regarding volatile agent use was effective at reducing FGFR, effectiveness was reduced without continued feedback. Use of more expensive volatile agents was not reduced by education regarding drug cost, and actually increased.
Continuous Cardiac Output in Septic Shock by Simulating a Model of the Aortic Input Impedance
Authors: Jellema Wilbert T. , Wesseling Karel H. , Groeneveld Johan A. B. , Stoutenbeek Chris P. , Thijs Lambertus G. , van Lieshout Johannes J.
Published: November 2003

Background

To compare continuous cardiac output obtained by simulation of an aortic input impedance model to bolus injection thermodilution (TDCO) in critically ill patients with septic shock.

Methods

In an open study, mechanically ventilated patients with septic shock were monitored for 1 (32 patients), 2 (15 patients), or 3 (5 patients) days. The hemodynamic state was altered by varying the dosages of dopamine, norepinephrine, or dobutamine. TDCO was estimated 189 times as the series average of four automated phase-controlled injections of iced 5% glucose, spread equally over the ventilatory cycle. Continuous model-simulated cardiac output (MCO) was computed from radial or femoral artery pressure. On each day, the first TDCO value was used to calibrate the model.

Results

TDCO ranged from 4.1 to 18.2 l/min. The bias (mean difference between MCO and TDCO) on the first day before calibration was -1.92 +/- 2.3 l/min (mean +/- SD; n = 32; 95% limits of agreement, -6.5 to 2.6 l/min). The bias increased at higher levels of cardiac output (P < 0.05). In 15 patients studied on two consecutive days, the precalibration ratio TDCO:MCO on day 1 was 1.39 +/- 0.28 (mean +/- SD) and did not change on day 2 (1.39 +/- 0.34). After calibration, the bias was -0.1 +/- 0.8 l/min with 82% of the comparisons (n = 112) < 1 l/min and 58% (n = 79) < 0.5 l/min, and independent of the level of cardiac output.

Conclusions

In mechanically ventilated patients with septic shock, changes in bolus TDCO are reflected by calibrated MCO over a range of cardiac output values. A single calibration of the model appears sufficient to monitor continuous cardiac output over a 2-day period with a bias of -0.1 +/- 0.8 l/min.
The Dose-Response of Caudal Ropivacaine in Children
Authors: Koinig Herbert , Krenn Claus G , Glaser Christian , Marhofer Peter , Wildling Eckart , Brunner Martin , Wallner Thomas , Grabner Claudia , Klimscha Walter , Semsroth Margot
Published: November 2003

Background

Ropivacaine, a new local anesthetic, is less cardiotoxic in adults and is less likely to cause motor blockade than is bupivacaine. The authors evaluated the clinical effectiveness and hemodynamic effects of ropivacaine compared with bupivacaine and the pharmacokinetics of ropivacaine when given for caudal blocks in 56 children 4.1 +/- 1.2 yr old (mean +/- SD).

Methods

Patients scheduled for inguinal hernia repair were randomly given a caudal injection (0.75 ml/kg) of ropivacaine, 0.25% (R0.25 group); ropivacaine, 0.5% (R0.5 group); or bupivacaine, 0.25% (B0.25 group). Postoperative measurements included the duration of analgesia, which was our primary outcome variable, and hemodynamic and respiratory monitoring for 4 h in the recovery room. Thereafter, analgesic requirements for the following 24 h were assessed by an independent observer on the ward using an observational pain-discomfort scale, which gives a cumulative score from 5 to 15 to estimate the quality of analgesia by assessment of behavioral objective parameters. Plasma levels of ropivacaine were measured before the procedure was started and 5, 10, 15, 20, 25, 30, and 45 min and 1, 2, 4, 6, 8, and 24 h after caudal block.

Results

A significantly longer (P < 0.0001) duration of analgesia (median [range]) was observed in the R0.5 group (1,440 [335-1,440] min), whereas the R0.25 group (208 [175-340] min) and the B0.25 group (220 [100-390] min) were comparable. All groups showed a significant decrease in mean arterial blood pressure and heart rate from baseline values, but differences between groups were not observed.

Conclusion

Ropivacaine is well tolerated and provides effective analgesia when given for caudal blockade in small children for inguinal hernia repair.
Epidural Clonidine or Bupivacaine as the Sole Analgesic Agent during and after Abdominal Surgery
Authors: De Kock Marc , Gautier Philippe , Pavlopoulou Athanassia , Jonniaux Marc , Lavand'homme Patricia
Published: November 2003

Background

The rationale of this study was to compare high-dose epidural clonidine with a more commonly used agent, such as bupivacaine. This was performed to give a more objective idea of the relative analgesic potency of epidural clonidine.

Methods

Sixty patients undergoing intestinal surgery during propofol anesthesia were studied. At induction, the patients received epidurally a dose of 10 micrograms/kg [corrected] clonidine in 7 ml saline followed by an infusion of 6 micrograms [corrected] x kg(-1) x h(-1) (7 ml/h) (group 1, n = 20), a dose of 7 ml bupivacaine, 0.5%, followed by 7 ml/h bupivacaine, 0.25% (group 2, n = 20), or a dose of 7 ml bupivacaine, 0.25%, followed by 7 ml/h bupivacaine, 0.125% (group 3, n = 20). Intraoperatively, increases in arterial blood pressure or heart rate not responding to propofol (0.5 mg/kg) were treated with intravenous alfentanil (0.05 mg/kg). Additional doses of propofol were given to maintain an adequate bispectral index. The epidural infusions were maintained for 12 h. In cases of subjective visual analogue pain scores up to 5 cm at rest or up to 8 cm during coughing, the patients were given access to a patient-controlled analgesia device.

Results

During anesthesia, patients in group 1 required less propofol than those in groups 2 and 3 (78 [36-142] mg vs. 229 [184-252] mg and 362 [295-458] mg; P < 0.05) and less alfentanil than patients in group 3 (0 [0-0] mg vs. 11 [6-20] mg; P < 0.05). Analgesia lasted 380 min (range, 180-645 min) in group 1 versus 30 min (range, 25-40 min) in group 2 and 22 min (range, 12.5-42 min) in group 3 (P < 0.05). There was no suggestion of a hemodynamic difference among the three groups except for heart rates that were significantly reduced in patients in group 1. Sedation scores were significantly higher in this group during the first 2 h postoperatively.

Conclusion

Our results show that high doses of epidural clonidine potentiate general anesthetics and provide more efficient postoperative analgesia than the two bupivacaine dosage regimens investigated.
Inhibition of Neutrophil Activation by Volatile Anesthetics Decreases Adhesion to Cultured Human Endothelial Cells
Authors: Mobert Jacqueline , Zahler Stefan , Becker Bernhard F. , Conzen Peter F.
Published: November 2003

Background

Polymorphonuclear leukocytes (neutrophils, PMNs) have been shown to mediate vascular and tissue injury, leading to so-called systemic inflammatory response syndrome. The authors evaluated the effect of volatile anesthetics on neutrophil adhesion to human endothelial cells, focusing on whether the inhibitory effect observed is linked to an alteration in the function of endothelial cells or neutrophils.

Methods

The adhesion of human PMNs was quantified using cultured human umbilical vein endothelial cells (HUVECs). The increase in the number of adhering PMNs was assessed when HUVECs (with 1 mM hydrogen peroxide), PMNs (with 10 nM N-formyl-methionyl-leucyl-phenylalanine), or both were prestimulated. To determine the influence of volatile anesthetics on the adhesion of PMNs, the experiments were performed in the absence or presence of 0.5, 1, and 2 minimum alveolar concentration halothane, isoflurane, or sevoflurane, whereby HUVECs, PMNs, or both were pretreated with gas.

Results

Activation of HUVECs with hydrogen peroxide or stimulation of PMNs with N-formyl-methionyl-leucyl-phenylalanine resulted in a 2.5-fold increase in PMN adhesion. Preincubation of PMNs, separately, with halothane, isoflurane, or sevoflurane, respectively, abolished enhanced neutrophil adhesion to hydrogen peroxide-activated HUVECs and adhesion of PMNs prestimulated with N-formyl-methionyl-leucyl-phenylalanine to unstimulated HUVECs (maximal effect at 1 minimum alveolar concentration). No decrease in adhesion was detected when only HUVECs were pretreated with volatile anesthetics. Additional exposure of HUVECs and PMNs to volatile anesthetics had no inhibitory effect on adhesion greater than that seen when only PMNs were treated. Appropriately, the volatile anesthetics abolished the upward regulation of the adhesion molecule CD11b on PMNs (as evaluated at 1 minimum alveolar concentration each), whereas 1 minimum alveolar concentration halothane failed to affect the expression of P-selectin, an adhesion molecule on endothelial cells.

Conclusions

This study indicates that halothane, isoflurane, and sevoflurane inhibit neutrophil adhesion to human endothelial cells at concentrations relevant to anesthesia in a static system. The effects appear to be mediated by inhibition of PMN activation; that is, by attenuating the upward regulation of neutrophil CD11b.
Comparison of the Effect-site keOs of Propofol for Blood Pressure and EEG Bispectral Index in Elderly and Younger Patients
Authors: Kazama Tomiei , Ikeda Kazuyuki , Morita Koji , Kikura Mutsuhito , Doi Matsuyuki , Ikeda Takehiko , Kurita Tadayoshi , Nakajima Yoshiki
Published: November 2003

Background

Drug effect lags behind the blood concentration. The goal of this investigation was to determine the time course of plasma concentration and the effects of propofol demonstrated by electroencephalogram or blood pressure changes and to compare them between elderly and young or middle-aged patients.

Methods

A target-controlled infusion was used to rapidly attain and maintain four sequentially increasing, randomly selected plasma propofol concentrations from 1 to 12 microg/ml in 41 patients aged 20-85 yr. The target concentration was maintained for about 30 min. Bispectral index (BIS), spectral edge frequency, and systolic blood pressure (SBP) were used as measures of propofol effect. Because the time courses of these measures following the started drug infusion showed an exponential pattern, the first-order rate constant for equilibration of the effect site with the plasma concentration (k(eO)) was estimated by fitting a monoexponential model to the effect versus time data resulting from the pseudo-steady-state propofol plasma concentration profile.

Results

The half-times for the plasma-effect-site equilibration for BIS were 2.31, 2.30, 2.29, and 2.37 min in patients aged 20-39, 40-59, 60-69, and 70-85 yr, respectively (n = 10 or 11 each). The half-times for SBP were 5.68, 5.92, 8.87, and 10.22 min in the respective age groups. All were significantly longer than for BIS (P < 0.05). The propofol concentration at half of the maximal decrease of SBP was significantly greater (P < 0.05) in the elderly than in the younger patients.

Conclusions

The effect of propofol on BIS occurs more rapidly than its effect on SBP. Age has no effect on the rate of BIS reduction with increasing propofol concentration, whereas with increasing age, SBP decreases to a greater degree but more slowly.