bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Incomplete Analgesia after Placement of an Epidural Catheter and Administration of Local Anesthetic for Women in Labor
Authors: Beilin Yaakov , Zahn Jeffrey , Bernstein Howard H. , Zucker-Pinchoff Barbara , Zenzen Wendy J. , Andres Lewis A.
Published: November 2003

Background

Approximately 15% of women still have pain after placement of an epidural catheter and administration of local anesthetic for labor analgesia. Two techniques frequently used to treat this pain were compared: (1) withdrawal of the catheter 1 cm and repeated dosing with additional local anesthetic, and (2) repeated dosing with additional local anesthetic without any catheter manipulation.

Methods

Fifteen minutes after placement of a multiple-orifice epidural catheter 5 cm into the epidural space and administration of 13 ml 0.25% bupivacaine to the parturient in labor, the adequacy of analgesia was assessed. All women who had incomplete analgesia were randomized (first intervention) to receive an additional 5 ml 0.25% bupivacaine (local-anestheticonly group) or to receive 5 ml 0.25% bupivacaine after first withdrawing the epidural catheter 1 cm (catheter-manipulation group). If after 15 min the woman still had pain, then (second intervention) the catheter was withdrawn 1 cm and an additional 5 ml 0.25% bupivacaine was administered to the local-anesthetic-only group, whereas 5 ml 0.25% bupivacaine was given to the catheter-manipulation group without further catheter manipulation. The success rate of the second intervention was assessed 15 min later.

Results

Seventy-eight women were enrolled in the study, 39 to each group. In the local-anesthetic-only group, 29 (74%) women were successfully treated with the first intervention and the remaining 10 (100%) were successfully treated with the second intervention. In the catheter-manipulation group, 30 (77%) were successfully treated with the first intervention and 7 (100%; 2 patients were not studied because of investigator error) were successfully treated with the second intervention (P=NS).

Conclusions

Administration of additional local anesthetic without first withdrawing the epidural catheter will effectively treat most women for whom analgesia is incomplete after the placement of an epidural catheter during labor.
Epidural Fentanyl Produces Labor Analgesia by a Spinal Mechanism
Authors: D'Angelo Robert , Gerancher J. C. , Eisenach James C. , Raphael Brenda L.
Published: November 2003

Background

The purpose of this study was to determine if epidural fentanyl produces analgesia in laboring patients by a primary spinal or supraspinal action.

Methods

Fifty-four parturients were randomized to receive epidural 0.125% bupivacaine plus one of three treatments: epidural saline-intravenous saline, epidural fentanyl (20 microg/h)-intravenous saline, or epidural saline-intravenous fentanyl (20 microg/h). The study treatments were administered by continuous infusion, whereas epidural bupivacaine use was patient controlled.

Results

Epidural bupivacaine use was significantly reduced by epidural (11.5+/-4.6 ml/h) but not by intravenous fentanyl (15.9+/-4.5 ml/h) compared with saline control (16+/-5.9 ml/ h). Analgesia characteristics and side effects were similar among groups.

Conclusions

Low-dose epidural infusions of fentanyl produce labor analgesia by a primary spinal action.
Desflurane Increases Pulmonary Alveolar-Capillary Membrane Permeability after Aortic Occlusion-Reperfusion in Rabbits
Authors: Nielsen Vance G. , Baird Manuel S. , McAdams Michelle L. , Freeman Bruce A.
Published: November 2003

Background

Pulmonary injury occurs after vascular surgery, with xanthine oxidase (an oxidant generator) released from reperfusing liver and intestines mediating a significant component of this injury. Because halogenated anesthetics have been observed to enhance oxidant-mediated injury in vitro, the authors hypothesized that desflurane would increase alveolar-capillary membrane permeability mediated by circulating xanthine oxidase after thoracic occlusion and reperfusion.

Methods

Rabbits were assigned to one of five groups: aorta occlusion groups administered desflurane (n=14), desflurane and tungstate (xanthine oxidase inactivator, n=12), fentanyl plus droperidol (n=13), and two sham-operated groups (desflurane, n=7 and fentanyl plus droperidol, n=7). Aortic occlusion was maintained for 45 min with a balloon catheter, followed by 3 h of reperfusion. Alveolar-capillary membrane permeability was assessed by measurement of bronchoalveolar lavage fluid protein. Xanthine oxidase activity was determined in plasma and lung tissue. Ascorbic acid content (an antioxidant) was determined in lung tissue.

Results

Desflurane was associated with significantly increased alveolar-capillary membrane permeability after aortic occlusion-reperfusion when compared with the fentanyl plus droperidol anesthesia or sham-operated groups (P < 0.05). Inactivation of xanthine oxidase abrogated the alveolar-capillary membrane compromise associated with desflurane. Although significantly greater than for sham-operated animals, plasma xanthine oxidase activities released after aortic occlusion-reperfusion were not different between the two anesthetics. There were no anesthetic-associated differences in lung tissue xanthine oxidase activity. However, desflurane anesthesia resulted in a significant reduction in lung ascorbic acid after aortic occlusion-reperfusion compared with the sham-operated animals.

Conclusions

Desflurane anesthesia increased xanthine oxidase-dependent alveolar-capillary membrane compromise after aortic occlusion-reperfusion in concert with depletion of a key tissue antioxidant.
The Effects of Epidural Morphine on Cardiac and Renal Sympathetic Nerve Activity in α-Chloralose-anesthetized Cats
Authors: Mori Takashi , Nishikawa Kiyonobu , Terai Takekazu , Yukioka Hidekazu , Asada Akira
Published: November 2003

Background

Epidural morphine yields postoperative pain relief and hemodynamic stability. However, the effects of epidural morphine on sympathetic tone are unclear. This study was designed to elucidate the effects of epidural morphine on cardiac (CSNA) and renal (RSNA) sympathetic nerve activity by direct measurement in anesthetized cats.

Methods

Thirty mongrel cats anesthetized with alpha-chloralose were randomly assigned to one of the following five groups: control (0.2 ml/kg thoracic epidural normal saline; n=5); thoracic epidural morphine (n=9); lumbar epidural morphine (n=6); vagotomized, sinoaortic denervated, thoracic epidural morphine (n=5); or intravenous morphine (n=5). Mean arterial pressure (MAP), heart rate (HR), CSNA, and RSNA were measured 0, 15, 30, 60, 90, and 120 min after saline or morphine (200 microg/kg) administration and 15 min after reversal with 200 microg naloxone given intravenously.

Results

In the control group, no changes in measured variables were found after either thoracic epidural saline or intravenous naloxone. Thoracic and lumbar epidural morphine both significantly reduced MAP, HR, CSNA, and RSNA 30 through 120 min after morphine administration (P < 0.05). These changes were reversed by intravenous naloxone. Changes after thoracic epidural morphine administration in vagotomized, baroreceptor-denervated cats were similar to those in intact cats. Intravenous morphine produced no significant changes except for a decrease in MAP, which was reversed by intravenous naloxone.

Conclusion

In contrast to intravenous morphine, thoracic and lumbar epidural morphine both inhibited cardiac and renal sympathetic nerve activity and consequently reduced MAP and HR in alpha-chloralose anesthetized cats.
In Vitro Hypothermia Enhances Platelet GPIIb-IIIa Activation and P-Selectin Expression
Authors: Faraday Nauder , Rosenfeld Brian
Published: November 2003

Background

A clinical bleeding diathesis is associated with hypothermia. Inhibition of platelet reactivity is the purported cause of this coagulopathy despite inconsistent evidence to support this hypothesis. To clarify the effect of temperature on intrinsic platelet function, platelet GPllb-IIIa activation and P-selectin expression were assessed under normothermic and hypothermic conditions in vitro.

Methods

Blood was obtained by venipuncture from healthy volunteers. Platelet activation was assessed by aggregometry and by cytometric analysis of platelet binding of fibrinogen, PAC-1, and P-selectin antibodies. Measurements were made at normothermia (37 degrees C), moderate hypothermia (33 degrees C), and profound hypothermia (22 degrees C) after stimulating samples with adenosine diphosphate (ADP), collagen, or thrombin receptor activating peptide.

Results

Agonist-induced platelet aggregation and fibrinogen binding were significantly greater at 22 degrees C and 33 degrees C than at 37 degrees C. Platelet fibrinogen binding values to 20 micro M ADP were 23,400, 14,300, and 9,700 molecules/platelet at 22 degrees C, 33 degrees C, and 37 degrees C, respectively. The aggregation responses of platelets that were cooled and rewarmed were indistinguishable from those of platelets maintained at 37 degrees C throughout the study. Platelet binding of PAC-1 and P-selectin antibodies was greater under hypothermic conditions.

Conclusions

Aggregation, fibrinogen binding, PAC-1 binding, and P-selectin antibody binding studies showed that platelet GPIIb-IIIa activation and alpha-granule release were enhanced at hypothermic temperatures. Thus hypothermia appears to increase the ability of platelets to respond to activating stimuli. The coagulopathy associated with hypothermia is not likely to be the result of an intrinsic defect in platelet function.
Effects of Small Concentrations of Volatile Anesthetics on Action Potential Firing of Neocortical Neurons In Vitro
Authors: Antkowiak Bernd , Helfrich-Forster Charlotte
Published: November 2003

Background

Volatile general anesthetics depress neuronal activity in the mammalian central nervous system and enhance inhibitory Cl- currents flowing across the gamma-aminobutyric acid A (GABA(A)) receptor-ion channel complex. The extent to which an increase in GABA(A)-mediated synaptic inhibition contributes to the decrease in neuronal firing must be determined, because many further effects of these agents have been reported on the molecular level.

Methods

The actions of halothane, isoflurane, and enflurane on the firing patterns of single neurons were investigated by extracellular recordings in organotypic slice cultures derived from the rat neocortex.

Results

Volatile anesthetics depressed spontaneous action potential firing of neocortical neurons in a concentration-dependent manner. The estimated median effective concentration (EC50) values were about one half the EC50 values for general anesthesia. In the presence of the GABA(A) antagonist bicuculline (20 microM), the effectiveness of halothane, isoflurane, and enflurane in reducing the discharge rates were diminished by 48-65%, indicating that these drugs act via the GABA(A) receptor.

Conclusions

Together with recent investigations, our results provide evidence that halothane, isoflurane, and enflurane reduced spontaneous action potential firing of neocortical neurons in cultured brain slices mainly by increasing GABA(A)-mediated synaptic inhibition. At concentrations, approximately one half the EC50 for general anesthesia, volatile anesthetics increased overall GABA(A)-mediated synaptic inhibition about twofold, thus decreasing spontaneous action potential firing by half.
Role of the Renal Cysteine Conjugate β-Lyase Pathway in Inhaled Compound A Nephrotoxicity in Rats
Authors: Kharasch Evan D. , Hoffman Gary M. , Thorning David , Hankins Douglas C. , Kilty Cormac G.
Published: November 2003

Background

The sevoflurane degradation product compound A is nephrotoxic in rats and undergoes metabolism to glutathione and cysteine S-conjugates, with further metabolism by renal cysteine conjugate beta-lyase to reactive intermediates. Evidence suggests that toxicity is mediated by renal uptake of compound A S-conjugates and metabolism by beta-lyase. Previously, inhibitors of the beta-lyase pathway (aminooxyacetic acid and probenecid) diminished the nephrotoxicity of intraperitoneal compound A. This investigation determined inhibitor effects on the toxicity of inhaled compound A.

Methods

Fischer 344 rats underwent 3 h of nose-only exposure to compound A (0-220 ppm in initial dose-response experiments and 100-109 ppm in subsequent inhibitor experiments). The inhibitors (and targets) were probenecid (renal organic anion transport mediating S-conjugate uptake), acivicin (gamma-glutamyl transferase), aminooxyacetic acid (renal beta-lyase), and aminobenzotriazole (cytochrome P450). Urine was collected for 24 h, and the animals were killed. Nephrotoxicity was assessed by histology and biochemical markers (serum BUN and creatinine; urine volume; and excretion of protein, glucose, and alpha-glutathione-S-transferase, a predominantly proximal tubular cell protein).

Results

Compound A caused dose-related proximal tubular cell necrosis, diuresis, proteinuria, glucosuria, and increased alpha-glutathione-S-transferase excretion. The threshold for toxicity was 98-109 ppm (294-327 ppm-h). Probenecid diminished (P < 0.05) compound A-induced glucosuria and excretion of alpha-glutathione-S-transferase and completely prevented necrosis. Aminooxyacetic acid diminished compound A-dependent proteinuria and glucosuria but did not decrease necrosis. Acivicin increased nephrotoxicity of compound A, and aminobenzotriazole had no consistent effect on nephrotoxicity of compound A.

Conclusions

Nephrotoxicity of inhaled compound A in rats was associated with renal uptake of compound A S-conjugates and cysteine conjugates metabolism by renal beta-lyase. Manipulation of the beta-lyase pathway elicited similar results, whether compound A was administered by inhalation or intraperitoneal injection. Route of administration does not apparently influence nephrotoxicity of compound A in rats.
Assessment of Clinical Performance during Simulated Crises Using Both Technical and Behavioral Ratings
Authors: Gaba David M. , Howard Steven K. , Flanagan Brendan , Smith Brian E. , Fish Kevin J. , Botney Richard
Published: November 2003

Background

Techniques are needed to assess anesthesiologists' performance when responding to critical events. Patient simulators allow presentation of similar crisis situations to different clinicians. This study evaluated ratings of performance, and the interrater variability of the ratings, made by multiple independent observers viewing videotapes of simulated crises.

Methods

Raters scored the videotapes of 14 different teams that were managing two scenarios: malignant hyperthermia (MH) and cardiac arrest. Technical performance and crisis management behaviors were rated. Technical ratings could range from 0.0 to 1.0 based on scenario-specific checklists of appropriate actions. Ratings of 12 crisis management behaviors were made using a five-point ordinal scale. Several statistical assessments of interrater variability were applied.

Results

Technical ratings were high for most teams in both scenarios (0.78 +/- 0.08 for MH, 0.83 +/- 0.06 for cardiac arrest). Ratings of crisis management behavior varied, with some teams rated as minimally acceptable or poor (28% for MH, 14% for cardiac arrest). The agreement between raters was fair to excellent, depending on the item rated and the statistical test used.

Conclusions

Both technical and behavioral performance can be assessed from videotapes of simulations. The behavioral rating system can be improved; one particular difficulty was aggregating a single rating for a behavior that fluctuated over time. These performance assessment tools might be useful for educational research or for tracking a resident's progress. The rating system needs more refinement before it can be used to assess clinical competence for residency graduation or board certification.
Persistent Alterations of the Autonomic Nervous System after Noncardiac Surgery
Authors: Amar David , Fleisher Martin , Pantuck Carol B. , Shamoon Harry , Zhang Hao , Roistacher Nancy , Leung Denis H. Y. , Ginsburg Ilana , Smiley Richard M.
Published: November 2003

Unlabelled

BACKGROUND. Changes in the sympathetic nervous system may be a cause of postoperative cardiovascular complications. The authors hypothesized that changes in both beta-adrenergic receptor (betaAR) function (as assessed in lymphocytes) and in sympathetic activity (assessed by plasma catecholamines and by heart rate variability [HRV] measurements obtained from Holter recordings) occur after operation.

Methods

The HRV parameters were measured in 28 patients having thoracotomy (n = 14) or laparotomy (n = 14) before and for as long as 6 days after operation. Transthoracic echocardiography was performed before and on postoperative day 2. Lymphocytes were also isolated from blood obtained before anesthesia and again on postoperative days 1, 2, 3, and 5 (or 6). They were used to examine betaAR number (Bmax) and cyclic adenosine monophosphate (cAMP) production after stimulation with isoproterenol and prostaglandin E1. In addition, plasma epinephrine, norepinephrine, and cortisol concentrations were determined at similar intervals.

Results

After abdominal and thoracic surgery, most time and all frequency indices of HRV decreased significantly, as did Bmax and basal and isoproterenol-stimulated cAMP production. The decrements in HRV correlated with those of Bmax and isoproterenol-stimulated cAMP throughout the first postoperative week and inversely correlated with the increase in heart rate. Plasma catecholamine concentrations did not change significantly from baseline values, but plasma cortisol levels did increase after operation in both groups. Left ventricular ejection fraction was normal in both groups and unaffected by surgery.

Conclusions

Persistent downregulation and desensitization of the lymphocyte betaAR/adenylyl cyclase system correlated with decrements in time and frequency domain indices of HRV throughout the first week after major abdominal or thoracic surgery. These physiologic alterations suggest the continued presence of adaptive autonomic regulatory mechanisms and may explain why the at-risk period after major surgery appears to be about 1 week or more.
A Comparison of the Respiratory Effects of Sevoflurane and Halothane in Infants and Young Children
Authors: Brown Karen , Aun Cindy , Stocks Janet , Jackson Elizabeth , Mackersie Angela , Hatch David
Published: November 2003

Background

This study compared the respiratory effects of sevoflurane with those of halothane in anesthetized infants and young children.

Methods

Infants were randomized to receive 1 minimum alveolar concentration (MAC) halothane or sevoflurane in a mixture of nitrous oxide and oxygen. Anesthetic management included the use of a laryngeal mask. Flow, airway pressure, and the end-tidal carbon dioxide pressure (PETCO2) were measured during spontaneous ventilation and airway occlusions. Respiratory inductive plethysmography was used to assess chest wall motion.

Results

Measurements were obtained in 30 infants and young children (mean (SD) age, 14.5 (5.9) months), 15 of whom received sevoflurane and 15 received halothane. Some respiratory depression, as indicated by a PETCO2 of 45 mmHg (6 kPa), was present in both groups. Minute ventilation and respiratory frequency were significantly lower during sevoflurane than halothane anesthesia (4.5 compared with 5.4 (1/ m2)/min, and 37.5 compared with 46.7 breaths/min, respectively, P < 0.05). There was no difference in respiratory drive, but the shape of the flow waveform differed according to anesthetic agent, with peak inspiratory flow reached later, and peak expiratory flow reached earlier, in the sevoflurane group. There was also significantly less thoracoabdominal asynchrony during sevoflurane anesthesia.

Conclusions

Minute ventilation and respiratory frequency were lower in infants during 1 MAC sevoflurane in nitrous oxide than during halothane anesthesia. However, these differences may not be clinically relevant at these concentrations, given the modest increase in PETCO2. Differences in parameters of breath timing and shape between sevoflurane and halothane suggest different effects of these anesthetic agents on ventilatory control.
The Effect of Propofol on Isolated Human Pregnant Uterine Muscle
Authors: Shin Young K. , Kim Young D. , Collea Joseph V.
Published: November 2003

Background

Propofol is an alternative to thiopental as an intravenous induction agent for cesarean section. Because it has relaxant effects on vascular and other smooth muscles, the authors set out to determine whether propofol has any effect on pregnant human uterine smooth muscle in an isolated preparation.

Methods

Myometrial specimens were excised from 10 parturients undergoing elective cesarean section. The muscle strips were suspended in tissue baths and isometric tension was recorded. After establishment of rhythmic contractions in the buffer solution as a control, propofol (0.5 to 10 microg/ml) in fat emulsion was applied cumulatively to the bath. The effect of the fat emulsion at equivalent concentrations was also examined.

Results

Propofol concentrations of 2.7 x 10(-6) M (0.5 microg/ml) and 1.1 x 10(-5) M (2 microg/ml) had no significant effect on the active tension developed by muscle contraction. However, propofol at concentration of 5.5 x 10(-5) M (10 microg/ml) reduced the active tension by 45% (P < 0.02) compared with the control value. The fat emulsion had no effects on the active tension.

Conclusions

These results imply that the decline in the active tension of muscle contraction was most likely caused by propofol and not by the fat emulsion. However, the propofol concentrations needed to produce a significant reduction in the uterine muscle tension appear to be much greater than the free propofol concentrations reported by others during cesarean section.
Comparison of pH-state and Alpha-stat Cardiopulmonary Bypass on Cerebral Oxygenation and Blood Flow in Relation to Hypothermic Circulatory Arrest in Piglets
Authors: Kurth Dean C. , O'Rourke Maureen M. , O'Hara Irene B.
Published: November 2003

Background

Deep hypothermic circulatory arrest is used in neonatal cardiac surgery. Recent work has suggested improved neurologic recovery after deep hypothermic arrest with pH-stat cardiopulmonary bypass (CPB) compared with alpha-stat CPB. This study examined cortical oxygen saturation (ScO2), cortical blood flow (CBF), and cortical physiologic recovery in relation to deep hypothermic arrest with alpha-stat or pH-stat CPB.

Methods

Sixteen piglets were cooled with pH-stat or alpha-stat CPB to 19 degrees C (cortex) and subjected to 60 min of circulatory arrest, followed by CPB reperfusion and rewarming and separation from CPB. Near infrared spectroscopy and laser Doppler flowmetry were used to monitor ScO2 and CBF. Cortical physiologic recovery was assessed 2 h after the piglets were separated from CPB by cortical adenosine triphosphate concentrations, cortical water content, CBF, and ScO2.

Results

During CPB cooling, ScO2 increased more with pH-stat than with alpha-stat bypass (123 +/- 33% vs. 80 +/- 25%); superficial and deep CBF were also greater with pH-stat than with alpha-stat bypass (22 +/- 25% vs. -56 +/- 22%, 3 +/- 19% vs. -29 +/- 28%). During arrest, ScO2 half-life was greater with pH-stat than with alpha-stat bypass (10 +/- 2 min vs. 7 +/- 2 min), and cortical oxygen consumption lasted longer with pH-stat than with alpha-stat bypass (36 +/- 8 min vs. 25 +/- 8 min). During CPB reperfusion, superficial and deep CBF were less with alpha-stat than with pH-stat bypass (-40 +/- 22% vs. 10 +/- 39%, -38 +/- 28% vs. 5 +/- 28%). After CPB, deep cortical adenosine triphosphate and CBF were less with alpha-stat than with pH-stat bypass (11 +/- 6 pmole/mg vs. 17 +/- 8 pmole/mg, -24 +/- 16% vs. 16 +/- 32%); cortical water content was greater with alpha-stat than with pH-stat bypass (superficial: 82.4 +/- 0.3% vs. 81.8 +/- 1%, deep: 79.1 +/- 2% vs. 78 +/- 1.6%).

Conclusions

Cortical deoxygenation during hypothermic arrest was slower after pH-stat CPB. pH-stat bypass increased the prearrest ScO2 and arrest ScO2 half-life, to increase the cortical oxygen supply and slow cortical oxygen consumption. Improved cortical physiologic recovery after hypothermic arrest was suggested with pH-stat management.
A Re-examination of Tetrodotoxin for Prolonged Duration Local Anesthesia
Authors: Kohane Daniel S. , Yieh Jamie , Lu Nu T. , Langer Robert , Strichartz Gary R. , Berde Charles B.
Published: November 2003

Background

Highly potent toxins such as tetrodotoxin that block sodium channels with great specificity have been studied for many years and can provide prolonged blockade when coadministered with vasoconstrictors or conventional local anesthetics. Their utility has been constrained, however, by systemic toxicity. The authors examined the efficacy of tetrodotoxin with and without epinephrine or bupivacaine for producing prolonged-duration sciatic nerve blockade in the rat, and they assessed the degree of concomitant toxicity.

Methods

Rats received percutaneous sciatic nerve blockade using tetrodotoxin with and without epinephrine or bupivacaine. A subset received subcutaneous injections at the nuchal midline. Nociceptive, proprioceptive, and motor blockade were quantified using contralateral leg responses as controls for systemic effects.

Results

Tetrodotoxin without epinephrine produced sciatic nerve blockade, but with considerable toxicity at most effective doses. Epinephrine reduced the median effective concentration of tetrodotoxin for nociception from 37.6 to 11.5 microM and prolonged its duration, such that reversible blocks lasting > 13 h were achieved. Epinephrine reduced measures of systemic distribution and increased the median lethal dose of tetrodotoxin from 40 to 53.6 nmole/kg, thus more than quadrupling the therapeutic index. Bupivacaine increased the local anesthetic potency of tetrodotoxin, reduced its systemic toxicity, and, when coinjected subcutaneously, increased the median lethal dose from 43.7 to 47.7 nmole/kg. The addition of epinephrine did not further improve the effectiveness of the bupivacaine-tetrodotoxin combination.

Conclusion

Combinations of epinephrine or bupivacaine with tetrodotoxin or with other high-potency toxins active on sodium channels should be examined for the potential to provide clinically useful, prolonged nerve blockade.
Lack of Correlation between the Reduction of Sevoflurane MAC and the Cerebellar Cyclic GMP Concentrations in Mice Treated with 7-Nitroindazole
Authors: Ichinose Fumito , Mi Wei-dong , Miyazaki Miyuki , Onouchi Tsuneko , Goto Takahisa , Morita Shigeho
Published: November 2003

Background

Although inhibition of nitric oxide synthase (NOS) has been reported to be antinociceptive and to reduce the threshold of general anesthesia, the mechanism of action is largely unknown. Specifically, the relation between the minimum alveolar concentration (MAC)-reducing effects of NOS inhibition and cyclic guanosine monophosphate (cGMP) concentrations in the brain has not been defined. To further characterize the effects of NOS inhibition, the authors studied the relation between the MAC of sevoflurane and the cGMP concentration of the brain after acute and chronic treatment with a neuronally selective NOS inhibitor, 7-nitroindazole (7-NI).

Methods

Sevoflurane MAC and cerebellar cGMP concentrations were determined in mice after acute intraperitoneal administration or after 1, 2, 3, and 4 days of gavage feeding of 7-NI. After acute or chronic treatment with 7-NI, the mice were separated into two groups. Sevoflurane MAC was measured by a tail-clamp method in the first group, and cerebellar cGMP concentrations were measured by enzyme-linked immunosorbent assay in the second group of the mice.

Results

In mice, acute intraperitoneal administration of 7-NI dose dependently decreased sevoflurane MAC and cerebellar cGMP; and 4-day-long gavage feeding with 7-NI (500 mg/ kg, every 8 h) time dependently decreased cerebellar cGMP, but sevoflurane MAC was reduced only for the first 2 days and returned to its baseline after 3 days of 7-NI feeding.

Conclusions

Although an acute selective inhibition of neuronal NOS decreases sevoflurane MAC and cerebellar cGMP concentrations in mice, there was a dissociation between the two parameters during long-term neuronal NOS inhibition. There may be cGMP-independent compensatory mechanisms that mediate nociception when NOS is chronically inhibited.
Volatile Anesthetic Additivity and Specificity in Saccharomyces cerevisiae
Authors: Wolfe Darren , Hester Paul , Keil Ralph L.
Published: November 2003

Background

In animals, combinations of volatile anesthetics are additive for inducing anesthesia. Furthermore, although there is a correlation between lipophilicity and anesthetic potency, not all volatile lipophilic compounds are anesthetic. Previously the authors demonstrated the effects of volatile anesthetics on the eukaryote Saccharomyces cerevisiae (yeast). To further relate anesthetic action in this organism to mammals, anesthetic additivity and effects of volatile, lipophilic nonanesthetics were studied. In addition, yeast pleiotropic drug-resistance (Pdr) mutants, which confer resistance to various lipophilic compounds, were tested to determine if they are involved in anesthetic response.

Methods

Yeast strains were grown to saturation in liquid culture, diluted, plated on various solid media, incubated, and scored for growth.

Results

Combinations of volatile anesthetics inhibit growth of wild-type (Zzz+) but not anesthetic-resistant (Zzz-) strains when additive concentrations equal 1 minimum inhibitory concentration (MIC). Two volatile, lipophilic compounds that are nonanesthetic in mammals do not inhibit yeast growth. Zzz- mutants remain sensitive to drugs used to identify yeast PDR genes. Conversely Pdr strains, which are resistant to various lipophilic compounds, remain sensitive to volatile anesthetics.

Conclusions

Yeast growth is inhibited in an additive manner by volatile anesthetics. Volatile, lipophilic compounds devoid of anesthetic activity in mammals do not inhibit yeast growth. Zzz- mutants appear to be specifically resistant to volatile anesthetics and distinct from known Pdr mutants. These results suggest that volatile anesthetics behave in a parallel manner in yeast and mammals, making yeast a useful model to investigate the molecular effects of these compounds in living cells.
Effects of Sevoflurane and Isoflurane on Renal Function and on Possible Markers of Nephrotoxicity
Authors: Higuchi Hideyuki , Sumita Shinji , Wada Hiroki , Ura Tatsuya , Ikemoto Takeshi , Nakai Tetsuji , Kanno Masuyuki , Satoh Tetsuo
Published: November 2003

Background

Low-flow sevoflurane anesthesia is associated with increasing circuit concentrations of compound A, which is nephrotoxic in rats, but the effect of compound A and low-flow sevoflurane anesthesia on renal function in humans is unclear. The authors compared the effects of high- and low-flow sevoflurane and isoflurane anesthesia on renal function and on several possible markers of nephrotoxicity in humans.

Methods

Forty-two patients without preexisting renal disease underwent either low-flow isoflurane (1 l/min, n = 14), low-flow sevoflurane (1 l/min, n 14), or high-flow sevoflurane (6 l/min, n = 14) anesthesia for body-surface-area surgery scheduled to last at least 4 h. Twenty-four-hour urinary excretion of N-acetyl-beta-glucosaminidase (NAG), beta2-microglobulin, protein, glucose, blood urea nitrogen (BUN), and serum creatinine concentrations were measured before and after anesthesia.

Results

There were no differences in blood urea nitrogen, creatinine, and creatinine clearance among the three groups after anesthesia. Increased urinary N-acetyl-beta-glucosaminidase excretions were seen in the low-flow and high-flow sevoflurane groups, but not in the low-flow isoflurane group (P < 0.01). Ten patients in the low-flow sevoflurane group had 24-h urinary excretion of protein that exceeded the normal ranges after anesthesia, but only one patient in the isoflurane and none in the high-flow sevoflurane groups had this.

Conclusions

Low-flow sevoflurane anesthesia was associated with mild and transient proteinuria. However, the observed proteinuria was not associated with any changes in blood urea nitrogen, creatinine, and creatinine clearance in these patients with no preexisting renal disease.
Intermittent CPAP
Authors: Bratzke Edward , Downs John B. , Smith Robert A.
Published: November 2003

Background

Airway pressure-release ventilation provides ventilation comparable to controlled mechanical ventilation (CMV), but with lower peak airway pressures and less dead-space ventilation. To obtain these advantages for patients administered general anesthesia, the authors (1) designed a mode similar to airway pressure-release ventilation, intermittent continuous positive airway pressure (CPAPI), and compared its efficiency with that of CMV; and (2) assessed the accuracy of end-tidal carbon dioxide tension (PETCO2) as a monitor of the partial pressure of carbon dioxide in arterial blood (PaCO2) during CPAPI compared with during CMV.

Methods

Twenty anesthetized, tracheally intubated patients received baseline CMV that produced a PETCO2 of approximately 35 mmHg and a pulse oximetry value > 90%. Patients were assigned to undergo alternating trials of CMV and CPAPI. During CPAPI, CPAP was applied to the airway, removed for 1 s, and reapplied at a rate equal to the ventilator rate during CMV. The difference between the carbon dioxide tension in arterial blood and end-tidal gas [P(a-ET)CO2] and the calculation of PaCO2/minute ventilation quantified the efficiency of ventilation. Data were summarized as mean +/- SD and compared using the Student's t-test.

Results

Peak airway pressure (13+/-2 vs. 23+/-5 cm H2O; P < 0.001) and minute ventilation (3.5+/-1 vs. 4.6+/-1.2 l/min; P < 0.0001) were lower during CPAPI than during CMV. The value for PaCO2/minute ventilation (11.1+/-2.9 vs. 7.9+/-2.6 mmHg x l(-1) x min(-1); P < 0.0001) was greater during CPAPI. P(a-ET)CO2 was always greater during CMV (6.3+/-1.6 vs. 1.7+/-0.9 mmHg; P < 0.0001) and was never > 3.5 mmHg during CPAPI.

Conclusions

During CPAPI, less ventilation was necessary to produce a PaCO2 comparable to that during CMV. This represents a significant reduction in dead-space ventilation, improved efficiency of ventilation, and a lower value for P(a-ET)CO2. Compared with CMV, CPAPI also improves the accuracy of PETCO2 as a monitor of PaCO2.
A Comparison of Left Ventricular Performance Indices Measured by Transesophageal Echocardiography with Automated Border Detection
Authors: Declerck Christ , Hillel Zak , Shih Henry , Kuroda Maxine , Connery Cliff P. , Thys Daniel M.
Published: November 2003

Background

Automated border detection (ABD) allows semiautomated measurement of left ventricular (LV) areas. They can be combined with left ventricular pressure signals to generate pressure-area loops and pressure-dimension indices of contractility. This study compared conventional indices of ventricular performance (fractional area change [FAC] and circumferential fiber shortening [Vcfc]) with pressure-dimension indices of contractility. A secondary aim was to compare the effects of volatile anesthetics on the indices.

Methods

Using transesophageal echocardiography with automated border detection, FAC and Vcfc were obtained in 23 patients after cardiopulmonary bypass. Left ventricular pressures were obtained with a left ventricular catheter. Preload reduction by inferior vena caval occlusion was used to obtain end-systolic elastance (Ees), preload recruitable stroke force (PRSF), and dP/dtmax x EDA(-1) (EDA = end-diastolic area). In 11 patients, the measurements were repeated at 1 end-tidal minimum alveolar concentration of halothane or isoflurane. The results are expressed as mean +/- SD.

Results

After cardiopulmonary bypass, FAC was 31.1+/-7.9%, Vcfc was 0.6+/-0.2 circ x s(-1), Ees was 25.8+/-11.6 mmHg x cm(-2), PRSF was 60.8+/-26.6 mmHg, and dP/dtmax x EDA(-1) was 245+/-123.4 mmHg x s(-1) x cm(-2). At 1 minimum alveolar concentration of a volatile anesthetic agent, FAC, Vcfc, and dP/dtmax x EDA(-1) remained unchanged. Significant decreases in Ees (19%) and PRSF (28%) were observed.

Conclusions

The association between pressure-dimension indices and Vcfc or FAC was weak or nonexistent. A reduction in myocardial contractility induced by the administration of volatile anesthetic agents was detected by Ees and PRSF, but not by FAC, Vcfc, or dP/dtmax x EDA(-1). After myocardial revascularization, Ees and PRSF appear more sensitive than FAC or Vcfc for measuring changes in contractility.
Intraoperative Determination of Cardiac Output Using Multiplane Transesophageal Echocardiography
Authors: Perrino Albert C. , Harris Stephen N. , Luther Martha A.
Published: November 2003

Background

Limitations in the imaging views that can be obtained with transesophageal echocardiography (TEE) have hindered development of a widely adopted Doppler method for cardiac output (CO) monitoring. The authors evaluated a CO technique that combines steerable continuous-wave Doppler with the imaging capabilities of two-dimensional multiplane TEE.

Methods

From the transverse plane transgastric, short-axis view of the left ventricle, the imaging array was rotated to view the left ventricular outflow tract (LVOT) and ascending aorta. Steerable continuous-wave Doppler was subsequently used to measure aortic blood flow velocities. Aortic valve area was determined using a triangular orifice model. Matched thermodilution and Doppler CO measurements were obtained serially during surgery.

Results

The left ventricular outflow tract was imaged in 32 of 33 patients (97%). Data analysis reveal a mean difference between techniques of -0.01 l/min, and a standard deviation of the differences of 0.56 l/min. Multiple regression showed a correlation of r = 0.98 between intrasubject changes in CO. Multiplane TEE correctly tracked the direction of 37 of 38 serial changes in thermodilution CO but with a modest 14% underestimation of the magnitude of these changes.

Conclusions

These results indicate that multiplane TEE can provide an alternative method for the intraoperative measurement of CO. The ability of the rotatable imaging array to align with the left ventricular outflow tract and the need for only minimal adjustments in probe position advance the utility of intraoperative TEE.
Transnasal Butorphanol Is Effective for Postoperative Pain Relief in Children Undergoing Myringotomy
Authors: Bennie Ruth E. , Boehringer Leigh A. , Dierdorf Stephen F. , Hanna Mark P. , Means Lyn J.
Published: November 2003

Background

More than 70% of children require analgesics after bilateral myringotomy and tube placement (BMT). Because anesthesia for BMT is generally provided by face mask without placement of an intravenous catheter, an alternative route for analgesia administration is needed. Transnasal butorphanol is effective in relieving postoperative pain in adults and children. The effectiveness of transnasal butorphanol for postoperative pain management in children undergoing BMT was studied.

Methods

This double-blinded, placebo-controlled study compared the postoperative analgesic effects of transnasal butorphanol administered after the induction of anesthesia. Sixty children classified as American Society of Anesthesiologists physical status 1 or 2 who were aged 6 months or older and scheduled for elective BMT were randomized to receive transnasal placebo or 5, 15, or 25 microg/kg butorphanol. Postoperative pain was assessed using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) on arrival in the postanesthesia care unit and at 5, 10, 15, 30, 45, and 60 min.

Results

The CHEOP scores were significantly less in the 25 microg/kg transnasal butorphanol group compared with controls. Significantly fewer children received rescue analgesia in the 25 microg/kg transnasal butorphanol group compared with controls (n = 1 and 8, respectively; P = 0.02).

Conclusions

Transnasal butorphanol given in a dose of 25 microg/kg after induction of anesthesia provided adequate postoperative pain relief in children undergoing BMT.
Volatile Anesthetics Do Not Alter Bradykinin-induced Release of Nitric Oxide or L-Citrulline in Crystalloid Perfused Guinea Pig Hearts
Authors: Fujita Satoshi , Roerig David L. , Chung Wynda W. , Bosnjak Zeljko J. , Stowe David F.
Published: November 2003

Background

Nitric oxide (NO) and L-citrulline (L-cit) are released by endothelial NO synthase (eNOS) to induce vasodilation via guanylyl cyclase and cyclic guanosine monophosphate (cGMP). Volatile anesthetics directly reduce vascular muscle tone, but their effects on the eNOS cGMP pathway is controversial. The aim of this study was to examine the effects of anesthetics on bradykinin-induced increases in flow, NO, and L-cit in isolated hearts.

Methods

Guinea pig hearts were isolated, perfused at 55 mmHg with a crystalloid or erythrocyte perfusate at 37 degrees C, and heart rate, left ventricular pressure, coronary flow (CF), effluent pH, and oxygen tension were monitored. Effluent [NO] was measured by a Clark-type electrode (sensitivity > or = 1 nM = 3 pA) with a selectively permeable membrane. Effluent [L-cit] was measured by chromatography. Before, during, and after exposure to halothane, isoflurane, or sevoflurane, hearts were infused with as much as 100 nM bradykinin to induce increases in CF and effluent release of NO and L-cit.

Results

In crystalloid-perfused hearts, 10 nm bradykinin produced maximal concentration-dependent increases in CF (87+/-2%), [NO] (24+/-4 nM), NO release (128+/-18 pmol x g(-1) x min(-1)), and [L-cit] (58+/-8 nM). Isoflurane slightly increased CF but not NO. Anesthetics did not alter the bradykinin-induced CF, NO slope relationship, or change [L-cit]. In erythrocyte-perfused hearts, isoflurane also did not alter the bradykinin-induced increase in CF and decrease in percentage of oxygen extracted.

Conclusions

This is the first study to simultaneously measure CF with bradykinin-induced changes in [NO] and [L-cit] in the presence of halothane, isoflurane, and sevoflurane in intact hearts. The study shows for the first time that volatile anesthetics do not alter the CF to NO relationship and suggests that NO production, NO release, and NO vasodilatory effects mediated by the eNOS cGMP pathway are not significantly affected by anesthetics in crystalloid or erythrocyte-perfused guinea pig hearts.
Nitric Oxide Inhibits Neutrophil Adhesion during Experimental Extracorporeal Circulation
Authors: Chello Massimo , Mastroroberto Pasquale , Marchese Antonietta R. , Maltese Giovanni , Santangelo Ermenegildo , Amantea Bruno
Published: November 2003

Background

Myocardial and pulmonary injuries often occur after cardiopulmonary bypass, mediated in part by neutrophil activation and adhesion to endothelial cells. The effects of nitric oxide (NO) administration on neutrophil adhesion to endothelial cells after simulated extracorporeal circulation were investigated.

Methods

Two identical extracorporeal circulation circuits were primed with fresh human blood and circulated for 2 h at 37 degrees C. Nitric oxide at a 40-ppm concentration was added to one of the oxygenators in each pair. Neutrophil CD11b/CD18 expression and their adhesion to human umbilical vein endothelial cell monolayers were assayed in leukocytes isolated from samples drawn from the circuit 30, 60, 90, and 120 min after circulation began. In another series of experiments, blocking monoclonal antibodies to both neutrophil CD11b and CD18 were incubated with polymorphonuclear leukocytes after removal from the circuit before the adhesion assay.

Results

After 60 min of circulation, the neutrophils from NO-treated circuits showed significantly reduced CD11b/CD18 surface expression compared with the control group. There was also a significant reduction in neutrophil-endothelial adhesion in the NO group after 120 min of circulation. Monoclonal antibodies to both CD11b and CD18 significantly inhibited the adhesion of polymorphonuclear leukocytes at endothelial cells after 120 min of circulation.

Conclusions

These results confirm that neutrophil activation occurs during cardiopulmonary bypass. The addition of NO to the circuits of extracorporeal circulation significantly affects neutrophil adhesion to endothelial cells.
Effects of Intraabdominanlly Insufflated Carbon Dioxide and Elevated Intraabdominal Pressure on Splanchnic Circulation
Authors: Blobner Manfred , Bogdanski Ralph , Kochs Eberhard , Henke Julia , Findeis Alexander , Jelen-Esselborn Sabine
Published: November 2003

Background

Intraabdominally insufflated carbon dioxide (CO2) during laparoscopy may have a specific effect on splanchnic circulation that may be unrelated to the effects of increased intraabdominal pressure alone. Therefore, the influences of insufflation with CO2 versus air on splanchnic circulation were compared.

Methods

Pigs were chronically instrumented for continuous recording of mesenteric artery, portal venous, inferior vena cava, and pulmonary arterial blood flow and portal venous pressure. After induction of anesthesia, CO2 or air was insufflated in 14 and 10 pigs, respectively. With the pigs in the supine position, intraabdominal pressure was increased in steps of 4 mmHg up to 24 mmHg by graded gas insufflation.

Results

During air insufflation, mesenteric artery vascular resistance was unchanged, whereas mesenteric arterial blood flow decreased with increasing intraabdominal pressure. Shortly after CO2 insufflation to an intraabdominal pressure of 4 mmHg, mean arterial pressure, mesenteric arterial blood flow, and mesenteric arterial vascular resistance were increased by 21%, 12% and 9%, respectively. Subsequently, with the onset of CO2 resorption in the third minute, mean arterial pressure declined to baseline values and mesenteric arterial vascular resistance declined to 85% of baseline values, whereas mesenteric arterial blood flow continued to increase to a maximum of 24% higher than baseline values. At steady-state conditions during CO2 insufflation, mesenteric arterial blood flow was increased up to an intraabdominal pressure 16 mmHg but decreased at higher intraabdominal pressures.

Conclusions

In contrast to air insufflation, intraabdominal insufflation of CO2 resulted in a moderate splanchnic hyperemia at an intraabdominal pressure < or = 12 mmHg. At higher intraabdominal pressure values, pressure-induced changes became more important than the type of gas used.