bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addition of Epinephrine to Intrathecal Bupivacaine and Sufentanil for Ambulatory Labor Analgesia
Authors: Campbell David C. , Banner Robert , Crone Lesley-Ann , Gore-Hickman Wendy , Yip Ray W. 
Published: November 2003

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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