bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reengineering Intravenous Drug and Fluid Administration Processes in the Operating Room
Authors: Fraind Deborah B. , Slagle Jason M. , Tubbesing Victor A. , Hughes Samuel A. , Weinger Matthew B. 
Published: November 2003

Background
A reengineering approach to intravenous drug and fluid administration processes could improve anesthesia care. In this initial study, current intravenous administration tasks were examined to identify opportunities for improved design.

Methods
After institutional review board approval was obtained, an observer sat in the operating room and categorized, in real time, anesthesia providers' activities during 35 cases ( approximately 90 h) into 66 task categories focused on drug/fluid tasks. Both initial room set-up at the beginning of a typical workday and cardiac and noncardiac general anesthesia cases were studied. User errors and inefficiencies were noted. The time required to prepare de novo a syringe containing a mock emergency drug was measured using a standard protocol.

Results
Drug/fluid tasks consumed almost 50 and 75%, respectively, of the set-up time for noncardiac and cardiac cases. In 8 cardiac anesthetics, drug/fluid tasks comprised 27 +/- 6% (mean +/- SD) of all prebypass clinical activities. During 20 noncardiac cases, drug/fluid tasks comprised 20 +/- 8% of induction and 15 +/- 7% of maintenance. Drug preparation far outweighed drug administration tasks. Inefficient or error prone tasks were observed during drug/fluid preparation (e.g., supply acquisition, waste disposal, syringe labeling), administration (infusion device failure, leaking stopcock), and organization (workspace organization and navigation, untangling of intravenous lines). Anesthesia providers (n = 21) required 35 +/- 5 s to prepare a mock emergency drug.

Conclusions
Intravenous drug and fluid administration tasks account for a significant proportion of anesthesia care, especially in complex cases. Current processes are inefficient and may predispose to medical error. There appears to be substantial opportunity to improve quality and cost of care through the reengineering of anesthesia intravenous drug and fluid administration processes. General design requirements are proposed.
Motion of the Diaphragm in Patients with Chronic Obstructive Pulmonary Disease while Spontaneously Breathing versus during Positive Pressure Breathing after Anesthesia and Neuromuscular Blockade
Authors: Kleinman Bruce S. , Frey Kerry , VanDrunen Mark , Sheikh Taqdees , DiPinto Donald , Mason Robert , Smith Theodore 
Published: November 2003

Background
Diaphragmatic excursion during spontaneous ventilation (SV) in normal supine volunteers is greatest in the dependent regions (bottom). During positive pressure ventilation (PPV) after anesthesia and neuromuscular blockade and depending on tidal volume, the nondependent region (top) undergoes the greatest excursion, or the diaphragm moves uniformly. The purpose of this study was to compare diaphragmatic excursion (during SV and PPV) in patients with chronic obstructive pulmonary disease (COPD) with patients having normal pulmonary function.

Methods
Twelve COPD patients and 12 normal control subjects were compared. Cross-table diaphragmatic fluoroscopy was performed while patients breathed spontaneously. After anesthetic induction and pharmacologic paralysis and during PPV, diaphragmatic fluoroscopy was repeated. For analytic purposes, the diaphragm was divided into three segments: top, middle, and bottom. Percentage of excursion of each segment during SV and PPV in normal subjects was compared with the percentage of excursion of each segment in patients with COPD.

Results
There was no significant difference in the pattern of regional diaphragmatic excursion (as a percentage of total excursion)-top, middle, bottom-when comparing COPD patients with control subjects during SV and PPV. In the control subjects, regional diaphragmatic excursion was 16 +/- (5), 33 +/- (5), 51 +/- (4) during SV and 49 +/- (13), 32 +/- (6), 19 +/- (9) during PPV. In COPD patients, regional diaphragmatic excursion was 18 +/- (7), 34 +/- (5), 49 +/- (7) during SV and 47 +/- (10), 32 +/- (6), 21 +/- (9) during PPV.

Conclusion
Regional diaphragmatic excursion in patients with COPD during SV and PPV is similar to that in persons with normal pulmonary function.
Results of Contracture Tests with Halothane, Caffeine, and Ryanodine Depend on Different Malignant Hyperthermia-associated Ryanodine Receptor Gene Mutations
Authors: Fiege Marko , Wappler Frank , Weisshorn Ralf , Ulrich Gerbershagen Mark , Steinfath Markus , Schulte am Esch Jochen 
Published: November 2003

Background
More than 20 mutations in the gene encoding for the ryanodine receptor (RYR1), a Ca2+ release channel of the skeletal muscle sarcoplasmic reticulum, have been found to be associated with malignant hyperthermia (MH). This study was designed to investigate the effects of different mutations in the RYR1 gene on contracture development in in vitro contracture tests (IVCT) with halothane, caffeine, and ryanodine.

Methods
Ninety-three MH-susceptible (MHS) patients, diagnosed by the standard IVCT with halothane and caffeine, were included in this prospective study. Surplus muscle specimens were used for an IVCT with 1 microm ryanodine. The contracture course during the ryanodine IVCT was described by the attainment of different time points: onset time of contracture and times when contracture reached 2 mN or 10 mN. In addition, all patients were screened for mutations of the RYR1 gene.

Results
In 36 patients, four different mutations of the RYR1 gene (C487-T, G1021-A, C1840-T, G7300-A) were found. The IVCT threshold concentrations of halothane and caffeine were lower in patients with the C487-T mutation compared with patients without a detected mutation in the RYR1 gene. In the IVCT with ryanodine, contracture levels of 2 mN and 10 mN were reached earlier in muscle specimens from patients with C487-T, C1840-T, and G7300-A mutations compared with specimens from patients with the G1021-A mutation and patients without detected mutation in the RYR1 gene.

Conclusions
The differences between the groups in the halothane and caffeine IVCT threshold concentrations and in the time course of contracture development in the ryanodine IVCT underline the hypothesis that certain mutations in the RYR1 gene could make the ryanodine receptor more sensitive to specific ligands. This may be an explanation for varying clinical symptoms of MH crisis in humans.
Memory Function during Propofol and Alfentanil Anesthesia
Authors: Kerssens Chantal , Lubke Gitta H. , Klein Jan , van der Woerd Andries , Bonke Benno 
Published: November 2003

Background
Conscious recall and implicit memory have been shown to depend on hypnotic state as measured by electroencephalographic (EEG) bispectral index (BIS). A third expression of memory (unconscious-controlled memory) was recently observed after moderate to light sedation (BIS, 70-80). The present study investigated memory function during deep sedation (BIS, 60-70). As memory effects are small, the authors studied potential predictors of individual differences in memory performance.

Methods
Memory function and speed of information processing were assessed in 56 outpatients before surgery. During propofol anesthesia supplemented with alfentanil, patients heard a series of words while anesthesia was titrated to BIS, 60-70. In between words, response to command was assessed using the Isolated Forearm Technique. The authors tested memory with a word stem completion task and process dissociation procedure to distinguish explicit from implicit effects.

Results
Mean (+/- SD) BIS during word presentation was 64.0 +/- 3. Patients with conscious recall of verbal commands (n = 9) did not recall or recognize presented words. Even so, the process dissociation procedure revealed evidence of memory by a significantly higher hit rate in the inclusion condition (0.26) than in the exclusion condition (0.12). Patients without conscious recall showed no evidence of memory for presented words. Hit scores correlated significantly with scores in the preoperative memory test (r = 0.35).

Conclusions
The authors found evidence of weak explicit memory function during anesthesia titrated to BIS, 60-70. The observations strongly suggest that postoperative memory relates to awareness during anesthesia, but the nature of this relation remains unclear. Memory seems more likely in patients with good preoperative memory performance.
Method of Preload Reduction during LVPVR Analysis of Systolic Function
Authors: Haney Michael F. , Johansson Göran , Häggmark Sören , Biber Björn 
Published: November 2003

Background
A graded preload reduction during analysis of the left ventricular pressure-volume relationship (LVPVR) is required for derivation of end-systolic elastance (Ees) and preload recruitable stroke work (PRSW). The authors aimed to measure serial changes in these systolic function parameters before and during planned circulatory interventions using two different methods of preload alteration: a positive airway pressure plateau (APP) and inferior vena cava occlusion (IVCO).

Methods
In eight animals, measurements were made at 38 degrees, 30 degrees, 32 degrees, 34 degrees, and posthypothermia 38 degrees C. In an additional eight animals, isoflurane, adrenaline, and aorta occlusion (balloon catheter occluder) were administered in series, each with a preintervention control measurement. Left ventricular volume was measured by conductance. Paired measurements of the systolic function parameters Ees and PRSW, each derived with two preload methods, were analyzed for bias.

Results
Circulatory alterations were achieved with the temperature, isoflurane, adrenaline, and aorta occlusion interventions. Measured changes in Ees and PRSW from control to intervention showed a strong correlation and no significant bias for APP in relation to IVCO. The APP-derived absolute values for Ees and PRSW demonstrated a consistent positive bias compared with IVCO.

Conclusion
The APP method for preload reduction during LVPVR analysis detected changes in Ees and PRSW during the circulatory interventions in this model that were not different than those detected using another preload reduction method, IVCO. APP and IVCO are not interchangeable methods for preload reductions during LVPVR absolute quantitation of systolic function, and each needs to be used serially.
Peripheral Nerve Injury Alters the α2Adrenoceptor Subtype Activated by Clonidine for Analgesia
Authors: Duflo Frédéric , Li Xinhui , Bantel Carsten , Pancaro Carlo , Vincler Michelle , Eisenach James C. 
Published: November 2003

Background
Previous studies suggest that the alpha adrenoceptor subtype is the target for spinally administered alpha -adrenergic agonists, clonidine, for pain relief. However, ST 91, a preferential alpha adrenoceptor subtype agonist, induces antinociception, and intrathecally administered alpha antisense oligodeoxynucleotide decreases antinociception induced by clonidine in the rat, suggesting non-A sites may be important as well. Therefore, the authors examined the subtype of alpha adrenoceptor activated by clonidine and ST 91 in normal rats and those with nerve injury-induced hypersensitivity.

Methods
The same mechanical stimulus was applied to normal rats and those following spinal nerve ligation, and the effect of intrathecal clonidine and ST 91 on withdrawal threshold to the stimulus was determined. To further examine subtypes, animals were spinally pretreated with vehicle, BRL 44408 (an alpha subtype-preferring antagonist), and ARC 239 (an alpha subtype-preferring antagonist).

Results
In normal animals, clonidine's effect was diminished by pretreatment with either antagonist, whereas ST 91's antinociceptive effect was solely blocked by pretreatment with ARC 239. In nerve-injured animals, the antihypersensitivity action of both clonidine and ST 91 was blocked by administration of ARC 239, whereas BRL 44408 was ineffective.

Conclusions
These data agree with previous studies supporting that the alpha adrenoceptor is important to the antinociceptive effect of clonidine in normal animals. Nerve injury alters this and results in a total reliance on alpha adrenoceptors.
Isoflurane Alters Angiotensin II–Induced Ca2+Mobilization in Aortic Smooth Muscle Cells from Hypertensive Rats
Authors: Samain Emmanuel , Bouillier Hélène , Rucker-Martin Catherine , Mazoit Jean-Xavier , Marty Jean , Renaud Jean-François , Dagher Georges 
Published: November 2003

Background
Angiotensin II (AngII) is a potent vasoconstrictor involved in the short-term control of arterial blood pressure. Isoflurane was reported to decrease vascular tone through an alteration of vascular smooth muscle cell vasomotor response to several agonists, but its effect on AngII signaling is not known. On the other hand, vascular response to AngII is altered in hypertension. In this study, the authors tested the hypothesis that (1) isoflurane alters AngII-induced intracellular Ca mobilization in aortic vascular smooth muscle cell from Wistar Kyoto and spontaneously hypertensive rats, and (2) this effect could be associated with an alteration of the organization of microtubular network, reported to be involved in AngII signaling.

Methods
The effect of 0.5-3% isoflurane was studied (1) on AngII (10 m)-induced intracellular Ca mobilization, intracellular Ca release from internal stores, and Ca influx in Fura-2 loaded cultured aortic vascular smooth muscle cell isolated from 6-week-old Wistar Kyoto and spontaneously hypertensive rats, using fluorescent imaging microscopy; and (2) on the organization of cytoskeletal elements, using immunofluorescence labeling.

Results
In both stains, isoflurane decreased in a concentration-dependent manner AngII-induced intracellular Ca mobilization, Ca release from internal stores, and Ca influx through nifedipine-insensitive Ca channels. This effect occurred at a lower concentrations of isoflurane in Wistar Kyoto rats than in spontaneously hypertensive rats. In both strains, the effect of isoflurane on AngII- Ca mobilization was abolished by impairment with nocodazole, vinblastine, or paclitaxel of microtubules polymerization. Isoflurane directly altered tubular network organization in a concentration-dependent and reversible manner.

Conclusions
Isoflurane decreased AngII-induced Ca mobilization at clinically relevant concentrations, suggesting that vascular response to AngII could be altered during isoflurane anesthesia. The hypertensive strain was found less sensitive than the normotensive one. In both strains, the isoflurane effect was associated with a microtubular network interaction.
Dexmedetomidine Increases the Cocaine Seizure Threshold in Rats
Authors: Whittington Robert A. , Virag Laszlo , Vulliemoz Yvonne , Cooper Thomas B. , Morishima Hisayo O. 
Published: November 2003

Background
Central alpha adrenoceptors have been demonstrated to play an important role in the control of seizure activity; moreover, alpha adrenoceptors have been linked to electroencephalogram changes associated with cocaine. The purpose of this study was to determine if dexmedetomidine, a highly selective alpha -adrenoceptor agonist, alters the threshold for cocaine-induced seizure activity in rats.

Methods
Sprague-Dawley rats received a cocaine infusion (1.25 mg x kg(-1) x min(-1)) followed 15 min later by the coinfusion of either dexmedetomidine (20-microg/kg intravenous bolus followed by an infusion of 1 microg x kg(-1) x min(-1), CD group, n = 8) or an equal volume of saline (CS group, n = 8). Dexmedetomidine or saline were coinfused with cocaine until the onset of cocaine-induced seizures. Dopamine concentrations in the nucleus accumbens were measured by microdialysis paired with chromatography. To determine if changes in extracellular dopamine were related to the seizures, dopamine (1 microm) was continuously delivered to the nucleus accumbens in a separate group (DACD group, n = 6) retrograde microdialysis. These rats then received an intravenous cocaine infusion followed by dexmedetomidine in the same manner as the CD group.

Results
Dexmedetomidine significantly increased the dose of cocaine necessary to produce seizures. Seizures occurred at 25.0 +/- 7.7 and 49.3 +/- 14.8 min in CS and CD, respectively (P < 0.001). The ratio of the percent increase in accumbal dopamine to the cocaine dose at the onset of seizure activity was significantly lower in CD, 39.9 +/- 16.5, compared to CS, 82.2 +/- 46.5 (P = 0.04). Intraaccumbal administration of dopamine prevented the effects of dexmedetomidine on the cocaine seizure threshold.

Conclusions
These data suggest that dexmedetomidine increases the cocaine-induced seizure threshold possibly a mechanism related to the attenuation of the extracellular dopaminergic neurotransmitter response to cocaine.
Differential Effects of Bupivacaine on Intracellular Ca2+Regulation
Authors: Zink Wolfgang , Graf Bernhard M. , Sinner Barbara , Martin Eike , Fink Rainer H. A. , Kunst Gudrun 
Published: November 2003

Background
Bupivacaine produces skeletal muscle damage in clinical concentrations. It has been suggested that this may be caused by an increased intracellular level of [Ca2+]. Therefore, the aim of this study was to investigate direct intracellular effects of bupivacaine on Ca2+ release from the sarcoplasmic reticulum (SR), on Ca2+ uptake into the SR, and on Ca2+ sensitivity of the contractile proteins.

Methods
Saponin skinned muscle fibers from the extensor digitorum longus muscle of BALB/c mice were examined according to a standardized procedure described previously. For the assessment of effects on Ca2+ uptake and release from the SR, bupivacaine was added to the loading solution and the release solution, respectively. Force transients and force decays were monitored, and the position of the curve relating relative isometric force free [Ca2+] was evaluated in the presence or absence of bupivacaine.

Results
Bupivacaine induces Ca2+ release from the SR. In addition, the Ca2+ loading procedure is suppressed, resulting in smaller caffeine-induced force transients after loading in the presence of bupivacaine. The decay of caffeine-induced force transients is reduced by bupivacaine, and it also shifts [Ca2+]-force relation toward lower [Ca2+].

Conclusions
These data reveal that bupivacaine does not only induce Ca2+ release from the SR, but also inhibits Ca2+ uptake by the SR, which is mainly regulated by SR Ca2+ adenosine triphosphatase activity. It also has a Ca2+ -sensitizing effect on the contractile proteins. These mechanisms result in increased intracellular [Ca2+] concentrations and may thus contribute to its pronounced skeletal muscle toxicity.
Does the A118G Polymorphism at the μ-opioid Receptor Gene Protect against Morphine-6-Glucuronide Toxicity?
Authors: Lötsch Jörn , Zimmermann Michael , Darimont Jutta , Marx Claudia , Dudziak Rafael , Skarke Carsten , Geisslinger Gerd 
Published: November 2003

Background
Some, but not all, patients with renal dysfunction suffer from side effects after morphine administration because of accumulation of the active metabolite morphine-6-glucuronide (M6G). The current study aims to identify genetic causes that put patients at risk for, or protect them from, opioid side effects related to high plasma M6G. Candidate genetic causes are the single nucleotide polymorphism (SNP) A118G of the mu-opioid-receptor gene (OPRM1), which has recently been identified to result in decreased potency of M6G, and mutations in the MDR1-gene coding P-glycoprotein, of which morphine and M6G might be a substrate.

Methods
Two men, aged 87 and 65 yr, with renal failure (creatinine clearance of 6 and 9 ml/min) received 30 mg/day oral morphine for pain treatment. Both patients had sufficient analgesia from morphine. However, while one patient tolerated morphine well despite high plasma M6G of 1735 nM, in the patient with M6G plasma concentrations of 941 nM it caused severe sleepiness and drowsiness. Patients were genotyped for known SNPs of the OPRM1 and MDR1 genes.

Results
The patient who tolerated morphine well despite high plasma M6G was a homozygous carrier of the mutated G118 allele of the mu-opioid-receptor gene, which has been previously related to decreased M6G potency. In contrast, the patient who suffered from side effects was "wild-type" for this mutation. No other differences were found between the OPRM1 and MDR1 genes.

Conclusions
The authors hypothesize that the A118G single nucleotide polymorphism of the mu-opioid-receptor is among the protective factors against M6G-related opioid toxicity. The observation encourages the search for pharmacogenetic reasons that cause interindividual variability of the clinical effects of morphine.
Early Effects of Acid-Base Management during Hypothermia on Cerebral Infarct Volume, Edema, and Cerebral Blood Flow in Acute Focal Cerebral Ischemia in Rats
Authors: Kollmar Rainer , Frietsch Thomas , Georgiadis Dimitrios , Schäbitz Wolf-Rüdiger , Waschke Klaus F. , Kuschinsky Wolfgang , Schwab Stefan 
Published: November 2003

Background
Although the frequency for the use of moderate hypothermia in acute ischemic stroke is increasing, the optimal acid-base management during hypothermia remains unclear. This study investigates the effect of pH- and alpha-stat acid-base management on cerebral blood flow (CBF), infarct volume, and cerebral edema in a model of transient focal cerebral ischemia in rats.

Methods
Twenty Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h during normothermic conditions followed by 5 h of reperfusion during hypothermia (33 degrees C). Animals were artificially ventilated with either alpha- (n = 10) or pH-stat management (n = 10). CBF was analyzed 7 h after induction of MCAO by iodo[(14)C]antipyrine autoradiography. Cerebral infarct volume and cerebral edema were measured by high-contrast silver infarct staining (SIS).

Results
Compared with the alpha-stat regimen, pH-stat management reduced cerebral infarct volume (98.3 +/- 33.2 mm(3) vs. 53.6 +/- 21.6 mm(3); P > or = 0.05 mean +/- SD) and cerebral edema (10.6 +/- 4.0% vs. 3.1 +/- 2.4%; P > or = 0.05). Global CBF during pH-stat management exceeded that of alpha-stat animals (69.5 +/- 12.3 ml x 100 g(-1) x min(-1) vs. 54.7 +/- 13.3 ml x 100 g(-1) x min; P > or = 0.05). The regional CBF of the ischemic hemisphere was 62.1 +/- 11.2 ml x 100 g(-1) x min(-1) in the pH-stat group versus 48.2 +/- 7.2 ml x 100 g(-1) x min(-1) in the alpha-stat group ( P> or = 0.05).

Conclusions
In the very early reperfusion period (5 h), pH-stat management significantly decreases cerebral infarct volume and edema as compared with alpha-stat during moderate hypothermia, probably by increasing CBF.