bluuebunny/crossref_metadata_2025 huggingface dataset:
Halothane and Isoflurane Inhibit Vasodilation Due to Constitutive but Not Inducible Nitric Oxide Synthase
Authors: Zuo Zhiyi , Tichotsky Alexandra , Johns Roger A.
Published: November 2003

Background

Inhalational anesthetics inhibit the nitric oxide-guanylyl cyclase signaling pathway, but the site of this inhibition is not yet clear. This study was designed to test the hypothesis that receptor activation or downstream signaling events leading to nitric oxide synthase activation are important sites for this inhibition by comparing the effect of anesthetics on vasodilation caused by the calcium-dependent constitutive endothelial nitric oxide synthase versus the calcium-independent inducible nitric oxide synthase.

Methods

Endothelium-intact or -denuded rat thoracic aorta rings preincubated with or without lipopolysaccharide were mounted for isometric tension measurement, constricted with phenylephrine, then relaxed with methacholine in the presence or absence of halothane (1-3%) or isoflurane (1-3%). The cyclic guanosine 3,5-monophosphate content in the endothelium-denuded rings preincubated with or without lipopolysaccharide in the presence or absence of 3% halothane or 3% isoflurane was quantified by radioimmunoassay. The activity of partially purified inducible nitric oxide synthase from activated mouse macrophage was assayed in the presence or absence of halothane (1-4%) or isoflurane (1-5%) by the conversion of 3H-L-arginine to 3H-L-citrulline.

Results

Halothane and isoflurane inhibited methacholine-stimulated, nitric oxide-mediated vasorelaxation in endothelium-intact aortic rings. Neither halothane nor isoflurane affected the vasorelaxation caused by basal endothelial nitric oxide synthase or inducible nitric oxide synthase activity. Neither anesthetic altered the cyclic guanosine 3,5-monophosphate increase caused by inducible nitric oxide synthase in the lipopolysaccharide-treated rings.

Conclusions

The results demonstrated that halothane and isoflurane inhibit only receptor/calcium-activated nitric oxide synthase action and that direct inhibition of nitric oxide synthase, soluble guanylyl cyclase, or an interaction with nitric oxide are not responsible for anesthetic inhibition of endothelium-dependent vasorelaxation.
Involvement of Glutamate Receptors in Strychnine- and Bicuculline-induced Allodynia in Conscious Mice
Authors: Onaka Masahiko , Minami Toshiaki , Nishihara Isao , Ito Seiji
Published: November 2003

Background

Glycine and gamma-aminobutyric acid (GABA) are inhibitory neurotransmitters that appear to be important in sensory processing in the spinal dorsal horn. Intrathecal administration of strychnine (strychnine-sensitive glycine receptor antagonist) or bicuculline (GABAA antagonist) was reported to induce allodynia. Although the strychnine-induced allodynia was shown to be mediated through the N-methyl-D-aspartate (NMDA)-type glutamate receptor, it is not clear whether the bicuculline-evoked-allodynia is mediated through the glutamate receptor system or how different the allodynia induced by strychnine and bicuculline are.

Methods

Male ddY mice weighing 20 +/- 2 g were used in this study. A 27-G stainless-steel needle attached to a microsyringe was inserted between the L5 and L6 vertebrae by a slight modification of the method of Hylden and Wilcox. Drugs in vehicle were injected slowly into the subarachnoid space to conscious mice at 22 +/- 2 degrees C. The volume of the intrathecal injection was 5 microliters. Studies on allodynia were carried out essentially according to the method of Yaksh and Harty.

Results

The intrathecal administration of strychnine or bicuculline in conscious mice resulted in allodynia elicited by nonnoxious brushing of the flanks. The maximum allodynia induced by strychnine was observed 5 min after intrathecal injection, but that induced by bicuculline was observed 10 min after intrathecal injection. Both responses gradually decreased over the experimental period of 50 min. The allodynia induced by strychnine was dose-dependently relieved by NMDA receptor antagonists (D-AP5, ketamine, and 7-C1-KYNA) and non-NMDA receptor antagonists (GAMS and CNQX) but not by metabotropic receptor antagonists (L-AP3 and L-AP4). On the other hand, allodynia induced by bicuculline was dose-dependently relieved by GAMS, L-AP3, and L-AP4, but not by D-AP5, ketamine, 7-C1-KYNA, and CNQX. Whereas the strychnine-evoked allodynia was dose-dependently relieved by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) and the soluble guanylate cyclase inhibitor methylene blue, the bicuculline-induced one was dose-dependently relieved by methylene blue but not by L-NAME.

Conclusions

These results demonstrate that both strychnine- and bicuculline-evoked allodynia were mediated through pathways that include the glutamate receptor and nitric oxide systems but in a different manner. the current study suggests that GABA and glycine may modulate responses to an innocuous tactile stimulus as inhibitory neurotransmitters at presynaptic and postsynaptic sites in the spinal cord, respectively.
Central Nervous System Sodium Channels Are Significantly Suppressed at Clinical Concentrations of Volatile Anesthetics
Authors: Rehberg Benno , Xiao Yong-Hong , Duch Daniel S.
Published: November 2003

Background

Although voltage-dependent sodium channels have been proposed as possible molecular sites of anesthetic action, they generally are considered too insensitive to be likely molecular targets. However, most previous molecular studies have used peripheral sodium channels as models. To examine the interactions of volatile anesthetics with mammalian central nervous system voltage-gated sodium channels, rat brain IIA sodium channels were expressed in a stably transfected Chinese hamster ovary cell line, and their modification by volatile anesthetics was examined.

Methods

Sodium currents were measured using whole cell patch clamp recordings. Test solutions were equilibrated with the test anesthetics and perfused externally on the cells. Anesthetic concentrations in the perfusion solution were determined by gas chromatography.

Results

All anesthetics significantly suppressed sodium currents at clinical concentrations. This suppression occurred through at least two mechanisms: (1) a potential-independent suppression of resting or open sodium channels, and (2) a hyperpolarizing shift in the voltage-dependence of channel inactivation resulting in a potential-dependent suppression of sodium currents. The voltage-dependent interaction results in IC50 values for anesthetic suppression of sodium channels that are close to clinical concentrations at potentials near the resting membrane potential.
Preemptive Analgesia: Intraperitoneal Local Anesthetic in Laparoscopic Cholecystectomy
Authors: Pasqualucci Alberto , De Angelis Verena , Contardo Riccardo , Colo Francesca , Terrosu Giovanni , Donini Annibale , Pasetto Alberto , Bresadola Fabrizio
Published: November 2003

Background

A controversy exists over the effectiveness and clinical value of preemptive analgesia. Additional studies are needed to define the optimum intensity, duration, and timing of analgesia relative to incision and surgery.

Methods

One hundred twenty patients undergoing laparoscopic cholecystectomy under general anesthesia plus topical peritoneal local anesthetic or saline were studied. Local anesthetic (0.5% bupivacaine with epinephrine) or placebo solutions were given as follows: immediately after the creation of a pneumoperitoneum (blocking before surgery), and at the end of the operation (blocking after surgery). Patients were randomly assigned to one of four groups of 30 patients each. Group A (placebo) received 20 ml 0.9% saline both before and after surgery, group B received 20 ml 0.9% saline before surgery and 20 ml local anesthetic after surgery, group C received 20 ml local anesthetic both before and after surgery, group P received 20 ml local anesthetic before and 20 ml 0.9% saline after surgery. Pain was assessed using a visual analog scale and a verbal rating scale at 0, 4, 8, 12, and 24 h after surgery. Metabolic endocrine responses (blood glucose and cortisol concentrations) and analgesic requirements also were investigated.

Results

Pain intensity (visual analog and verbal rating scales) and analgesic requirements were significantly less in the group receiving bupivacaine after surgery compared to placebo. However, in the groups receiving bupivacaine before surgery, both pain intensity and analgesic consumption were less than in the group receiving bupivacaine only after surgery. Blood glucose and cortisol concentrations 3 h after surgery were significantly less in groups receiving bupivacaine before surgery.

Conclusions

The results indicate that intraperitoneal local anesthetic blockade administered before or after surgery preempts postoperative pain relative to an untreated placebo-control condition. However, the timing of administration is also important in that postoperative pain intensity and analgesic consumption are both lower among patients treated with local anesthetic before versus after surgery.
Internal Jugular Vein and Carotid Artery Anatomic Relation as Determined by Ultrasonography
Authors: Troianos Christopher A. , Kuwik Richard J. , Pasqual John R. , Lim Alexander J. , Odasso David P.
Published: November 2003

Background

Cannulation of the internal jugular vein (IJV) is associated with a 95% success rate when external landmarks are used. Anatomic variability has been implicated as the cause for difficulty in cannulation without ultrasound. In contrast to an IJV located lateral to the carotid artery (CA), an IJV overlying the CA may result in CA puncture. The authors' purpose in this study was to examine, using ultrasound, the anatomic relation of the IJV and CA as viewed from the perspective of a cannulating needle.

Methods

Ultrasound imaging was used in 1,136 patients to examine the relation between the IJV and CA. A 7.5-MHz transducer was placed in the direction of a cannulating needle on the right neck at the apex of the angle formed by the division of the sternocleidomastoid muscle. A Polaroid photograph of the image was later scored by three blinded investigators according to the percentage of the CA overlaid by the IJV (0 to 4).

Results

Of the 1,136 Polaroid photographs of the ultrasound images, 1,009 were suitable for scoring. Fifty-four percent of all patients received a score of 4, which indicated that the IJV overlies more than 75% of the CA in an imaging plane positioned in the direction of a cannulating needle. Patients older than 60 yr were more likely to have this anatomy than patients younger than 60 yr (P < 0.05). None of the other patient characteristics recorded were predictive of this anatomic relation.

Conclusions

In a majority of patients, the IJV is not lateral to the CA in an ultrasound imaging plane positioned in the direction of a cannulating needle. Instead, the IJV overlies the CA in 54% of patients overall, predisposing these patients to CA puncture if the cannulating needle traverses the IJV.
Direct Inhibitory Mechanisms of Halothane on Human Platelet Aggregation
Authors: Kohro Shinji , Yamakage Michiaki
Published: November 2003

Background

Although halothane directly inhibits platelet aggregation, the mechanisms of this effect are still unknown. The current study aimed to clarify the inhibitory mechanisms of halothane on thrombin-induced human platelet aggregation by measuring (1) platelet-surface glycoprotein Ib expression, (2) the concentration of intracellular free Ca2+ ([Ca2+]i) measured simultaneously with aggregation, (3) the concentration of intracellular inositol 1,4,5-triphosphate, and (4) the concentration of intracellular cyclic 3',5'-adenosine monophosphate ([cAMP]i).

Methods

Washed platelet suspensions, obtained from healthy volunteers, were preincubated with halothane (0-2 mM) for 2 min and then exposed to 0.02 units/ml thrombin for 3 min. The glycoprotein Ib bound to fluorescein-labeled antibody was measured by fluorescence flow cytometry. [Ca2+]i was measured, simultaneously with aggregation, in Fura-2 (Ca2+ indicator)-loaded platelets by use of a fluorometer. Inositol 1,4,5-triphosphate and [cAMP]i were measured by radioimmunoassay.

Results

Halothane had no effect on glycoprotein Ib expression with or without thrombin. Halothane decreased the thrombin stimulated [Ca2+]i transient and inhibited platelet aggregation in a dose-dependent manner, both in the presence and in the absence of external Ca2+. Isoflurane had no apparent effect on either platelet aggregation or [Ca2+]i in the absence of external Ca2+. Halothane inhibited the increase in inositol 1,4,5-triphosphate induced by thrombin. Halothane moderately but significantly increased [cAMP]i, but the adenylate cyclase activator forskolin (which has the same inhibitory ability on aggregation as halothane) increased [cAMP]i to a much greater extent than did halothane.

Conclusions

Halothane inhibits thrombin-induced human platelet aggregation by decreasing [Ca2+]i without inhibiting agonist-receptor binding; the inhibitory effect of halothane on [Ca2+]i might be mediated by a decrease in inositol 1,4,5 triphosphate and in part by an increase in [cAMP]i.
Acetylcholine Stimulates the Release of Nitric Oxide from Rat Spinal Cord
Authors: Xu Zemin , Tong Chuanyao , Eisenach James C.
Published: November 2003

Background

Acetylcholine causes synthesis of nitric oxide in vascular endothelium, and presumptive evidence in vivo suggests spinally released acetylcholine causes antinociception and increased sympathetic nervous system activity via a nitric oxide mechanism. The purpose of this study was to determine, using a recently described bioassay system, whether acetylcholine stimulates nitric oxide release from spinal cord tissue in vitro.

Methods

Rat thoracolumbar spinal cord slices were incubated in a tissue chamber and perfused with Krebs-Henseleit solution. The perfusate was then passed through endotheliumdenuded rat aortic rings and their tension was measured. Vascular rings were preconstricted with phenylephrine, then were exposed to spinal cord perfusate with increasing concentrations (10(-12)-10(-4)M) of acetylcholine alone or with various antagonists.

Results

Acetylcholine perfusion of spinal tissue caused concentration-dependent relaxations of the aortic rings, an effect blocked by each of the muscarinic antagonists, atropine, pirenzepine, and AFDX-116. Acetylcholine-induced relaxation also was antagonized by an inhibitor of nitric oxide synthase (N-methyl-L-arginine), a nitric oxide scavenger (hemoglobin) and an inhibitor of guanylate cyclase (methylene blue).

Conclusions

These results demonstrate release of a vasorelaxant from spinal cord tissue by acetylcholine, which results from an action on muscarinic receptors and exhibits a pharmacology consistent with nitric oxide. Although precise anatomic localization of acetylcholine's action is not possible with this system, these results add to evidence that acetylcholine causes nitric oxide synthesis in the spinal cord.
Nitrous Oxide Depresses Spinal F Waves in Rats
Authors: Friedman Yaron , King Bryan S. , Rampil Ira J.
Published: November 2003

Background

Evoked, recurrent electromyographic activity (F waves) reflect alpha-motor neuron excitability. Based on observations that other inhaled anesthetics do so, we hypothesized that nitrous oxide, alone or in combination with isoflurane, would depress F-wave activity and correlate with depression of movement response to tail clamp or electric stimulation.

Methods

In study 1, the authors examined the effect of nitrous oxide in combination with isoflurane in 13 normocapnic Sprague-Dawley rats anesthetized with 1.0% isoflurane (0.7 minimum alveolar concentration) in oxygen. The tibial nerve was stimulated at the popliteal fossa, and evoked electromyographic activity [M (direct neuromuscular junctional response) and F waves] were recorded from ipsilateral foot muscles. The effect of the addition of 30% or 70% nitrous oxide was measured. F-wave amplitude/M-wave amplitude ratio (F/M) was determined from each stimulus-electromyographic response pair. F/M vs. movement response to 60-s tail clamp was assessed after each recording session. F-wave amplitude/M-wave amplitude ratio at adjacent doses that permitted and prevented movement were compared. In study 2, the authors examined the effect of (hyperbaric) nitrous oxide as the sole anesthetic agent on F waves. In 11 rats anesthetized with isoflurane, stimulation and recording electrodes were placed as described above, with additional electrodes for stimulation placed in the tail. Rats were placed in a pressure chamber pressurized with nitrous oxide/oxygen to 3.4 atm. Thirty m were allowed for isoflurane washout. Electromyographic activity was evoked and recorded at 1.0, 1.6, 2.2 and 2.7 atm N2O (random order). Movement in response to 60 s of 15 V, 50-Hz tail stimulation was evaluated after each recording session.

Results

Nitrous oxide with or without isoflurane produced a dose-dependent decrease in F/M. By interpolation of this data, the authors found that 2 atm N2O alone, or 44% N2O added to 1.0% isoflurane at 1.0 atm, produced 1.0 minimum alveolar concentration anesthesia. At the deepest level of isoflurane/ nitrous oxide that permitted movement, mean F/M was 20.6 +/- 17.5%; at the lowest concentration that blocked movement, rats had a mean F/M of 13.7 +/- 13.9% (P = 0.01). At the minimal hyperbaric nitrous oxide blocking movement, rats had a mean F/M of 3.7 +/- 2.9%, whereas the F/M at the highest nitrous oxide dose that permitted movement was 4.4 +/- 2.7% (P < 0.04).

Conclusions

Because nitrous oxide depressed F-wave but not M-wave activity, the data suggest a central (spinal) rather than neuromuscular junctional site of action of this agent. The direct correlation between nitrous oxide dose, F-wave amplitude depression, and surgical immobility suggests the possibility of using F-wave activity to predict the likelihood of anesthetic-induced immobility. However, the mechanism of action of nitrous oxide may differ from that of the potent inhaled agents.
Effects of Hypothermia, Pentobarbital, and Isoflurane on Postdepolarization Amino Acid Release during Complete Global Cerebral Ischemia
Authors: Nakashima Ken , Todd Michael M.
Published: November 2003

Background

Hypothermia and anesthetics may protect the brain during ischemia by blocking the release of excitatory amino acids. The effects of hypothermia (28 degrees C), pentobarbital, and isoflurane on postischemic excitatory amino acid concentrations were compared.

Methods

Rats were anesthetized with 0.8% halothane/50% N2O, vascular catheters were placed, and a glass microelectrode and microdialysis cannula were inserted into the cerebral cortex. Experimental groups were: (1) control, pericranial, t = 38 degrees C; (2) hypothermia, t = 28 degrees C; (3) pentobarbital, t = 38 degrees C; and (4) isoflurane, t = 38 degrees C. Halothane/N2O was continued in groups 1 and 2, whereas a deep burst-suppression or isoelectric electroencephalogram was achieved with the test drugs in groups 3 and 4. Cerebral metabolic rates were similar in groups 2, 3, and 4. After a baseline dialysis sample was collected, animals were killed with potassium chloride. The time to terminal depolarization was recorded, after which three consecutive 10-min dialysate samples were collected. Glutamate, aspartate, gamma-aminobutyric acid, and glycine concentrations were measured using high-performance liquid chromatography.

Results

Times to terminal depolarization were shorter in both pentobarbital and isoflurane groups than with hypothermia (103 +/- 15 and 127 +/- 10 vs. 195 +/- 20 s respectively, mean +/- SD). However, times to terminal depolarization in all three groups were longer than in control subjects (control = 70 +/- 9s). Postdepolarization concentrations of all compounds were lower in hypothermic animals (vs. normothermic control animals), but no reductions in glutamate, aspartate, or glycine concentrations were noted in pentobarbital or isoflurane groups. gamma-Aminobutyric acid concentrations were reduced by both anesthetics, but not to the same degree as with hypothermia.

Conclusions

Pentobarbital and isoflurane prolonged the time to terminal depolarization, but did not influence the rate at which the extracellular concentrations of glutamate, aspartate, or glycine increased. By contrast, hypothermia reduced the release of all excitatory amino acids. These differences may explain the greater protective efficacy of hypothermia in the face of cerebral ischemia.
Cardiac Risk of Noncardiac Surgery in Patients with Asymmetric Septal Hypertrophy
Authors: Haering Michael J. , Comunale Mark E. , Parker Robert A. , Lowenstein Edward , Douglas Pamela S. , Krumholz Harlan M. , Manning Warren J.
Published: November 2003

Background

Many data are available regarding cardiac risk in patients with coronary artery disease undergoing noncardiac surgery, but few data are available regarding risk for patients with hypertrophic cardiomyopathy and asymmetric septal hypertrophy.

Methods

Seventy-seven patients with asymmetric septal hypertrophy were identified in whom an echocardiogram had been performed within 24 months of noncardiac surgery. Patients' charts were reviewed for data regarding surgical operations, including length of surgery, type of anesthesia, and intravascular monitoring used. Data regarding adverse perioperative cardiac events also were gathered.

Results

Forty percent (n = 31) of patients had one or more adverse perioperative cardiac events, including one patient who had a myocardial infarction and ventricular tachycardia that required emergent cardioversion. There were no perioperative deaths. All 31 patients had minor outcomes. Of the 77 patients, perioperative congestive heart failure developed in 12 (16%). Factors associated with adverse cardiac events were increasing length of surgical time (P < 0.01) major surgery (P < 0.05), and intensity of monitoring (P < 0.05). Age, gender, resting outflow tract gradient, systolic anterior motion of the anterior mitral leaflet, prior myocardial infarction, severity of mitral regurgitation, type of anesthetic, septal thickness, and the interval between echocardiogram and surgery were not associated with the occurrence of adverse cardiac events.

Conclusion

Patients with asymmetric septal hypertrophy undergoing noncardiac surgery have a high incidence of adverse cardiac events, frequently manifested as congestive heart failure. However, irreversible cardiac morbidity and mortality was extremely low. Important independent risk factors for adverse outcome in all patients include major surgery and increasing duration of surgery.
Epidural Meperidine after Cesarean Section
Authors: Ngan Kee Warwick D. , Lam Kwok K. , Chen Phoon P. , Gin Tony
Published: November 2003

Background

Epidural meperidine is effective for postoperative analgesia, but the optimum dose has not been evaluated.

Methods

Five doses of epidural meperidine (12.5, 25, 50, 75, and 100 mg) given at the first request for analgesia after cesarean section were compared. Visual analog pain scores, duration of analgesia as defined by time to first patient-controlled epidural analgesia demand, plasma concentrations of meperidine, side effects, and subsequent 24-h consumption of meperidine were evaluated.

Results

All doses were effective, but patients took longer to become pain-free after 12.5 mg (median 30 min) compared with 25 mg (median 12 min, P = 0.038), and duration of analgesia was shorter after 12.5 mg (median 83 min) compared with 25 mg (median 165 min, P = 0.0005). Increasing dose to more than 25 mg did not improve onset or duration of analgesia. Plasma concentrations of meperidine were less than minimum effective analgesia concentration for all doses except 100 mg. There was more frequent nausea (P = 0.004) and dizziness (P = 0.0002) after 100 mg compared with smaller doses.

Conclusions

Epidural meperidine provides effective postoperative analgesia, although of relatively short duration. A single dose of 25 mg is superior to 12.5 mg, but there is no benefit from increasing the dose to 50 mg or greater.
Acute Pain and Central Nervous System Arousal Do Not Restore Impaired Hypoxic Ventilatory Response during Sevoflurane Sedation
Authors: Sarton Elise , Dahan Albert , Teppema Luc , van den Elsen Maarten , Olofsen Erik , Berkenbosch Aad , van Kleef Jack
Published: November 2003

Background

To quantify the effects of acute pain on ventilatory control in the awake and sedated human volunteer, the acute hypoxic ventilatory response was studied in the absence and presence of noxious stimulation before and during 0.1 minimum alveolar concentration sevoflurane inhalation.

Methods

Step decreases in end-tidal partial pressure of oxygen from normoxia into hypoxia (approximately 50 mmHg) were performed in 11 healthy volunteers. Four acute hypoxic ventilatory responses were obtained per subject: one in the absence of pain and sevoflurane (C), one in the absence of sevoflurane with noxious stimulation in the form of a 1-Hz electrical current applied to the skin over the tibial bone (C + P), one in the absence of pain during the inhalation of 0.1 minimum alveolar concentration sevoflurane (S), and one during 0.1 minimum alveolar concentration sevoflurane with noxious stimulation (S + P). The end-tidal partial pressure of carbon dioxide was held constant at a value slightly greater than baseline (44 mmHg). To assess the central nervous system arousal state, the bispectral index of the electroencephalogram was monitored. Values are mean +/- SE.

Results

Pain caused an increase in prehypoxic baseline ventilation before and during sevoflurane inhalation: C = 13.7 +/- 0.9 l.min-1, C + P = 16.0 +/- 1.0 l.min-1 (P < 0.05 vs. C and S), S = 12.7 +/- 1.2 l.min-1, and S + P = 15.9 +/- 1.1 l.min-1 (P < 0.05 vs. C and S). Sevoflurane decreased the acute hypoxic ventilatory response in the absence and presence of noxious stimulation: C = 0.69 +/- 0.20 l.min-1 (% change in arterial hemoglobin-oxygen saturation derived from pulse oximetry [SpO2])-1, C + P = 0.64 +/- 0.13 l.min-1.%SpO2(-1), S = 0.48 +/- 0.15 l.min-1.%SpO2(-1) (P < 0.05 vs. C and C + P) and S + P = 0.46 +/- 0.21 l.min-1.%SpO2(-1) (P < 0.05 vs. C and C + P). The bispectral indexes were C = 96.2 +/ 0.7, C + P = 97.1 +/- 0.4, S = 86.3 +/- 1.3 (P < 0.05), and S + P = 95.0 +/- 1.0.

Conclusions

The observation that acute pain caused an increase in baseline ventilation with no effect on the acute hypoxic ventilatory response indicates that acute pain interacted with ventilatory control without modifying the effect of low-dose sevoflurane on the peripheral chemoreflex loop. Acute pain increased the level of arousal significantly during sevoflurane inhalation but did not restore the approximately 30% depression of the acute hypoxic ventilatory response by sevoflurane. The central nervous system arousal state per se did not contribute to the impairment of the acute hypoxic ventilatory response by sevoflurane.
Density of Lumbar Cerebrospinal Fluid in Pregnant and Nonpregnant Humans
Authors: Richardson Michael G. , Wissler Richard N.
Published: November 2003

Background

Dextrose-free local anesthetics and opioids, alone and in combinations, are being used increasingly to provide subarachnoid anesthesia and analgesia. These dextrose-free drugs have been described as hypobaric by some and isobaric by others. To accurately classify anesthetics with regard to baricity, the density of cerebrospinal fluid (CSF) must be known. The authors sought to determine the exact density of human CSF, and determine whether CSF density is altered by pregnancy.

Methods

Density measurements accurate to 0.00001 g/ml were made at 37.00 degrees C, using a mechanical oscillation resonance frequency density meter. Cerebrospinal fluid samples were obtained from 44 patients during spinal anesthesia. Five groups were studied: men, and premenopausal, postmenopausal, term pregnant, and postpartum women.

Results

Mean CSF densities in men (1.00064 +/- 0.00012 g/ ml), postmenopausal women (1.00070 +/- 0.00018 g/ml), and nonpregnant premenopausal women (1.00049 +/- 0.00004 g/ ml) were significantly greater than in term pregnant (1.00030 +/- 0.00004 g/ml) and postpartum (1.00034 +/- 0.00005 g/ml) women. Cerebrospinal fluid density did not correlate with age.

Conclusions

Mean CSF density varies in different patient subpopulations. Pregnancy and the immediate postpartum period are associated with the lowest CSF densities. In addition, the cutoff values defining hypobaricity (mean CSF density minus three standard deviations) are greater than previously reported. Accurate CSF density values should be used when considering baricity as a mechanism for clinical observations of dextrose-free intrathecal local anesthetics and opioids. Gestational status also should be considered.
Phenylephrine Increases Cerebral Blood Flow during Low-flow Hypothermic Cardiopulmonary Bypass in Baboons
Authors: Schwartz Arthur E. , Minanov Oktavijan , Stone Gilbert J. , Adams David C. , Sandhu Aqeel A. , Pearson Mark E. , Kwiatkowski Pawel , Young William L. , Michler Robert E.
Published: November 2003

Background

Although low-flow cardiopulmonary bypass (CPB) has become a preferred technique for the surgical repair of complex cardiac lesions in children, the relative hypotension and decrease in cerebral blood flow (CBF) associated with low flow may contribute to the occurrence of postoperative neurologic injury. Therefore, it was determined whether phenylephrine administered to increase arterial blood pressure during low-flow CPB increases CBF.

Methods

Cardiopulmonary bypass was initiated in seven baboons during fentanyl, midazolam, and isoflurane anesthesia. Animals were cooled at a pump flow rate of 2.5 l.min-1.m-2 until esophageal temperature decreased to 20 degrees C. Cardiopulmonary bypass flow was then reduced to 0.5 l.min-1.m-2 (low flow). During low-flow CPB, arterial partial pressure of carbon dioxide (Pco2) and blood pressure were varied in random sequence to three conditions: (1) Pco2 30-39 mmHg (uncorrected for temperature), control blood pressure; (2) Pco2 50-60 mmHg, control blood pressure; and (3) Pco2 30-39 mmHg, blood pressure raised to twice control by phenylephrine infusion. Thereafter, CPB flow was increased to 2.5 l.min-1.m-2, and baboons were rewarmed to normal temperature. Cerebral blood flow was measured by washout of intraarterial 133Xe before and during CPB.

Results

Phenylephrine administered to increase mean blood pressure from 23 +/- 3 to 46 +/- 3 mmHg during low-flow CPB increased CBF from 14 +/- 3 to 31 +/- 9 ml.min-1.100 g-1, P < 0.05. Changes in arterial Pco2 alone during low flow bypass produced no changes in CBF.

Conclusions

Although low-flow CPB resulted in a marked decrease in CBF compared with prebypass and full-flow bypass, phenylephrine administered to double arterial pressure during low-flow bypass produced a proportional increase in CBF.
Multicenter Study of Target-Controlled Infusion of Propofol-Sufentanil or Sufentanil-Midazolam for Coronary Artery Bypass Graft Surgery
Authors: Jain Uday , Body Simon C. , Bellows Wayne , Wolman Richard , Mangano Christina Mora , Mathew Joseph , Youngs Elizabeth , Wilson Robert , Zhang Adam , Mangano Dennis T.
Published: November 2003

Background

The use of target-controlled infusions of anesthetics for coronary artery bypass graft surgery has not been studied in detail. The effects of target-controlled infusions of propofol or sufentanil, supplemented by infusions of sufentanil or midazolam, respectively, were evaluated and compared.

Methods

At 14 clinical sites, 329 patients were given a target-controlled infusion of propofol (n = 165) to produce effect-site concentration (Ce) of > or = 3-micrograms/ml or a target-controlled infusion of sufentanil (n = 164). Sufentanil or midazolam, respectively, also were infused. Systolic hypertension, hypotension, tachycardia, and bradycardia were assessed by measuring heart rate and blood pressure every minute during operation. Myocardial ischemia was assessed perioperatively by monitoring ST segment deviation via continuous three-lead Holter electrocardiography, and it was evaluated during operation by monitoring left ventricular wall motion abnormality via transesophageal echocardiography.

Results

The measured cardiovascular parameters were satisfactory and usually similar for the patients receiving propofol-sufentanil or sufentanil-midazolam. The primary endpoint of the percentage of patients with intraoperative ST segment deviation (23 +/- 6% vs. 24 +/- 6%, P = 0.86) did not differ significantly between the two groups. The incidence of left ventricular wall motion abnormality shown on transesophageal echocardiography before (19 +/- 4% vs. 26 +/- 4%, P = 0.25) and after (23 +/- 4% vs. 31 +/- 5%, P = 0.32) cardiopulmonary bypass also did not differ significantly for the two groups. Changes in intraoperative target concentration were more frequent with propofol-sufentanil anesthetic than with sufentanil-midazolam (11.7 +/- 7.1 vs. 7.3 +/- 3.6, P < 0.001). The incidence of intraoperative hypotension (77% vs. 55%, P < 0.001), the use of inotropic/vasopressor medications (93% vs. 84%, P = 0.01), and the administration of crystalloids (2.8 +/- 1.4 L vs. 2.4 +/- 1.2 L, P < 0.001) were significantly greater in the propofol-sufentanil group. Conversely, the incidence of intraoperative hypertension (43% vs. 54%, P = 0.05) and the use of antihypertensive/vasodilator medications (70% vs. 90%, P < 0.001) were significantly less in the propofol-sufentanil group.

Conclusions

Target-controlled infusions of propofol or sufentanil, supplemented by infusions of sufentanil or midazolam, respectively, were suitable to provide anesthesia for coronary artery bypass graft surgery. Continuous monitoring revealed a high prevalence of hemodynamic abnormalities. Despite greater hypotension in the propofol-sufentanil group and greater hypertension in the sufentanil-midazolam group, episodes of myocardial ischemia were similar for both groups and were not temporally related to episodes of hemodynamic abnormalities.
Effects of Dexmedetomidine on Hypoxia-evoked Glutamate Release and Glutamate Receptor Activity in Hippocampal Slices
Authors: Talke P. , Bickler P. E.
Published: November 2003

Background

The selective alpha(2) agonist dexmedetomidine may improve neurologic outcome after incomplete ischemia in animals when it is administered either before or after the start of the ischemic insult. To clarify further the mechanisms by which alpha(2) agonists may provide neuroprotective effects, the authors tested the hypotheses that dexmedetomidine decreases synaptic and extrasynaptic glutamate release stimulated by potassium chloride or hypoxia, and decreases postsynaptic glutamate receptor activity during aerobic or hypoxic conditions.

Methods

Glutamate released from brain slices (300-microns thick) from rat hippocampus was measured in a cuvette during two experimental stresses: (1) potassium chloride-evoked depolarization (30 mM) with and without 10 nM, 100 nM, or 1,000 nM dexmedetomidine; and (2) hypoxia (95% N2 - 5% CO2) with and without 100 nM dexmedetomidine. Glutamate release was quantified by fluorescence assay using 1 mM nicotinamide adenine dinucleotide, and 5 international units per ml glutamate dehydrogenase. The formation of nicotinamide dinucleotide reduced from nicotinamide adenine dinucleotide by glutamate dehydrogenase was measured fluorometrically (excitation light 340 nm, emission intensity 460 nm) in the solution above the slice. Glutamate receptor activity was determined by the change in cytosolic calcium concentration in CA1 neurons in the presence and absence of 100 nM dexmedetomidine during administration of N-methyl-D-aspartate (100 microM) and during simulated ischemic penumbra conditions (PO2 = 20 mmHg, glutamate 3 mM). Calcium concentration was measured using a microscope fluorometer in fura 2-loaded rat hippocampal brain slices.

Results

Dexmedetomidine attenuated potassium chloride-evoked glutamate release by 37%, 51%, (P = 0.03) and 27%, respectively, for the 10 nM, 100 nM, and 1,000 nM concentrations, and decreased (at 100 nM) the increase in glutamate release in response to hypoxia by 61% (P < 0.0001). Dexmedetomidine (100 nM) had no effect on N-methyl-D-aspartate or hypoxia plus 3 mM L-glutamate-mediated calcium changes.

Conclusions

The selective alpha(2)-adrenergic agonist dexmedetomidine decreases evoked glutamate release from hippocampal rat brain slices during depolarization or hypoxic stress, but does not alter calcium changes mediated by the stimulation of glutamate receptors during aerobic or hypoxic conditions.
Protective Effect of Stroma-free Methemoglobin during Cyanide Poisoning in Dogs
Authors: Breen Peter H. , Isserles Schlomo A. , Tabac Eric , Roizen Michael F. , Taitelman Uri Z.
Published: November 2003

Background

During fire exposure, cyanide toxicity can block aerobic metabolism. Oxygen and sodium thiosulfate are accepted therapy. However, nitrite-induced methemoglobinemia, which avidly binds cyanide, decreases oxygen-carrying capacity that is already reduced by the presence of carboxyhemoglobin (inhalation of carbon monoxide in smoke). This study tested whether exogenous stroma-free methemoglobin (SFmetHb) can prevent depression of hemodynamics and metabolism during canine cyanide poisoning.

Methods

In 10 dogs (weighing 18.8 +/- 3.5 kg) anesthetized with chloralose-urethane and mechanically ventilated with air, baseline hemodynamic and metabolic measurements were made. Then, 137 +/- 31 ml of 12 g% SFmetHb was infused into five dogs (SFmetHb group). Finally, the SFmetHb group and the control group (n = 5, no SFmetHb) received an intravenous potassium cyanide infusion (0.072 mg.kg-1.min-1) for 20 min. Oxygen consumption (VO2) was measured with a Datex Deltatrac (Datex Instruments, Helsinki, Finland) metabolic monitor and cardiac output (QT) was measured by pulmonary artery thermodilution.

Results

From baseline to cyanide infusion in the control group, QT decreased significantly (p < 0.05) from 2.9 +/- 0.8 to 1.5 +/- 0.4 l/min, mixed venous PCO2 (PvCO2) tended to decrease from 35 +/- 4 to 23 +/- 2 mmHg, PvO2 increased from 43 +/- 4 to 62 +/- 8 mmHg, VO2 decreased from 93 +/- 8 to 64 +/- 19 ml/min, and lactate increased from 2.3 +/- 0.5 to 7.1 +/- 0.7 mM. In the SFmetHb group, cyanide infusion did not significantly change these variables. From baseline to infused cyanide, the increases in blood cyanide (4.8 +/- 1.0 to 452 +/- 97 microM) and plasma thiocyanate cyanide (18 +/- 5 to 65 +/- 22 microM) in the SFmetHb group were significantly greater than those increases in the control group. SFmetHb itself caused no physiologic changes, except small decreases in heart rate and PvO2. Peak SFmetHb reached 7.7 +/- 1.0% of total hemoglobin.

Conclusions

Prophylactic intravenous SFmetHb preserved cardiovascular and metabolic function in dogs exposed to significant intravenous cyanide. Blood concentrations of cyanide, and its metabolite, thiocyanate, revealed that SFmetHb trapped significant cyanide in blood before tissue penetration.
Role Central Mu, Delta-1, and Kappa-1 Opioid Receptors in Opioid-induced Muscle Rigidity in the Rat
Authors: Vankova Miriana E. , Weinger Matthew B. , Chen Dong-Yi , Bronson J. Brian , Motis Valerie , Koob George F.
Published: November 2003

Background

Opioids appear to produce their physiologic effects by binding to at least three types of opioid receptors, the mu (mu), delta (delta), and kappa (kappa) receptors. Muscle rigidity occurs after administration of supra-analgesic doses of potent mu-preferring agonists like alfentanil. The role of different supraspinal opioid receptors in this rigidity has been addressed only recently. To elucidate the contribution of central mu, delta, and kappa receptors to muscle rigidity, the effects of intracerebroventricularly administered opioid receptor-selective agonists and antagonists on alfentanil-induced muscle rigidity were examined in rats.

Methods

Rats in which chronic intracerebroventricular cannulae had been implanted received an intracerebroventricular infusion of either saline or a mu (D-Ala2,N-Me-Phe4-Gly5-olenkephalin; DAMGO), delta(1) (D-Pen2,D-Pen5-enkephalin; DPDPE), or kappa(1) (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)- cyclohexyl)-benzene-acetamide methane sulfonate; U50,488H) opioid agonist. Ten minutes later, they received either saline or the mu-agonist alfentanil subcutaneously. Muscle rigidity was assessed using hindlimb electromyographic activity. Different groups of animals were pretreated with an intracerebroventricular infusion of either saline or a mu (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2; CTAP), delta (naltrindole), or kappa(1) (norbinaltorphimine) opioid antagonist before administration of either saline or a selective intracerebroventricular agonist.

Results

The mu agonist DAMGO alone dose-dependently induced muscle rigidity. This effect was antagonized by pretreatment with the mu-selective antagonist CTAP. Neither DPDPE nor U50,488H, when administered alone, affected muscle tone. However, both the delta(1) and kappa(1) agonists dose-dependently attenuated alfentanil-induced rigidity. This antagonism of alfentanil rigidity was abolished after pretreatment with the delta (naltrindole) and kappa(1) (nor-binaltorphimine) antagonists, respectively.

Conclusions

The present data demonstrate that whereas systemic opiate-induced muscle rigidity is primarily due to the activation of central mu receptors, supraspinal delta(1) and kappa(1) receptors may attenuate this effect. This finding is consistent with previous demonstrations of functional interactions between different central opioid receptor populations in other opiate effects, and could have important pharmacotherapeutic implications.
Effects of Isoflurane and Desflurane on Neurogenic Motor- and Somatosensory-evoked Potential Monitoring for Scoliosis Surgery
Authors: Bernard Jean-Marc , Pereon Yann , Fayet Guillemette , Guiheneuc Pierre
Published: November 2003

Background

Most techniques used to monitor spinal cord tracts are sensitive to the effects of anesthesia, particularly to volatile anesthetic agents. The aim of this prospective study was to show that evoked potentials recorded from the peripheral nerves after spinal cord stimulation, so-called neurogenic motor evoked potentials, are resistant to clinical concentrations of isoflurane or desflurane, compared with somatosensory-evoked potentials.

Methods

Twenty-three patients were studied during surgery to correct scoliosis. The background anesthetic consisted of a continuous infusion of propofol. Isoflurane (n = 12) or desflurane (n = 11) were then introduced to achieve 0.5 and 1.0 end-tidal minimum alveolar concentrations (MAC), both in 50% oxygen-nitrous oxide and in 100% oxygen. Somatosensory-evoked potentials were elicited and recorded using a standard method, defining cortical P40 and subcortical P29. Neurogenic motor-evoked potentials were elicited by electric stimulation of the spinal cord via needle electrodes placed by the surgeon in the rostral part of the surgical field. Responses were recorded from needle electrodes inserted in the right and left popliteal spaces close to the sciatic nerve. Stimulus intensity was adjusted to produce a supramaximal response; that is, an unchanged response in amplitude with subsequent increases in stimulus intensity. Measurements were obtained before introducing volatile agents and 20 min after obtaining a stable level of each concentration.

Results

Isoflurane and desflurane in both 50% oxygen-nitrous oxide and 100% oxygen were associated with a significant decrease in the amplitude and an increase in the latency of the cortical P40, whereas subcortical P29 latency did not vary significantly. Typical neurogenic motor-evoked potentials were obtained in all patients without volatile anesthetic agents, consisting of a biphasic wave, occurring 15 to 18 ms after stimulation, with an amplitude ranging from 1.3 to 4.1 microV. Latency or peak-to-peak amplitude of this wave was not significantly altered with isoflurane and desflurane, either in the presence or in the absence of nitrous oxide.

Conclusions

Compared with cortical somatosensory-evoked potentials, neurogenic motor-evoked potential signals are well preserved in patients undergoing surgery to correct scoliosis under general anesthesia supplemented with isoflurane or desflurane in concentrations as great as 1 MAC.
Cocaine-abusing Parturients Undergoing Cesarean Section
Authors: Kain Zeev N. , Mayes Linda C. , Ferris Cynthia A. , Pakes Juliana , Schottenfeld Richard
Published: November 2003

Background

Cocaine use in the United States is prevalent among pregnant women from inner city neighborhoods. To determine the anesthetic implications of cocaine use in parturients undergoing cesarean section delivery, the authors conducted a cohort study.

Methods

One thousand nine hundred seven women presenting for prenatal care were interviewed regarding substance abuse. Urine was analyzed for benzoylecgonine, tetrahydracannabinol, benzodiazepines, and opioids. Next all parturients who underwent cesarean section delivery were identified and their records reviewed for anesthetic and obstetric outcomes.

Results

Among the 51 women who were classified as cocaine abusers, the most frequent reasons for cesarean section were fetal distress (48%) and abruptio placenta (21%). In a multivariate model, cocaine abuse before delivery was shown to be an independent predictor of preoperative diastolic hypertension (F = 10.6, P = 0.01). Similarly, univariate analysis showed that immediately after intubation, diastolic blood pressure was significantly higher among parturients who used cocaine (99 +/- 13 mmHg v. 87 +/- 18 mmHg; P = 0.02). In contrast, epidural anesthesia was associated with hypotension significantly more often among cocaine-abusing parturients (44% vs. 10%; P = 0.04). A higher rate of perioperative wheezing was reported among patients who abused cocaine (16% vs. 6%; relative risk = 2.7); this finding, however, did not persist in multivariate analysis. Operative blood loss was similar in all groups (P = NS), and no ventricular dysrhythmias or cerebrovascular or coronary ischemic episodes were reported in any of the parturients.

Conclusions

Although cocaine-abusing parturients are at higher risk for interim peripartum events such as hypertension, hypotension, and wheezing episodes, there is no significant increase in rates of maternal morbidity or death.
Variation in Expert Opinion in Medical Malpractice Review
Authors: Posner Karen L. , Caplan Robert A. , Cheney Frederick W.
Published: November 2003

Background

Expert opinion in medical malpractice is a form of implicit assessment, based on unstated individual opinion. This contrasts with explicit assessment processes, which are characterized by criteria specified and stated before the assessment. Although sources of bias that might hinder the objectivity of expert witnesses have been identified, the effect of the implicit nature of expert review has not been firmly established.

Methods

Pairs of anesthesiologist-reviewers independently assessed the appropriateness of care in anesthesia malpractice claims. With potential sources of bias eliminated or held constant, the level of agreement was measured.

Results

Thirty anesthesiologists reviewed 103 claims. Reviewers agreed on 62% of claims and disagreed on 38%. They agreed that care was appropriate in 27% and less than appropriate in 32%. Chance-corrected levels of agreement were in the poor-good range (kappa = 0.37; 95% CI = 0.23 to 0.51).

Conclusions

Divergent opinion stemming from the implicit nature of expert review may be common among objective medical experts reviewing malpractice claims.