bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrent Hypoxemia in Young Children with Obstructive Sleep Apnea Is Associated with Reduced Opioid Requirement for Analgesia
Authors: Brown Karen A. , Laferrière André , Moss Immanuela Ravé 
Published: March 2004

Background
Obstructive sleep apnea (OSA) in children is often associated with recurrent hypoxemia during sleep. In developing animals, central opioid neuropeptide content is high, and opioid receptors are up-regulated after recurrent hypoxia. The authors hypothesized that children with recurrent hypoxemia due to OSA might have altered central opioid functionality that could affect their responsiveness to opioid drugs. Using a retrospective database, we assessed the relation of age and preoperative oxygen saturation to the cumulative postoperative morphine dose administered for analgesia in children with OSA undergoing adenotonsillectomy.

Methods
Inclusion criteria were (1) adenotonsillectomy for OSA; (2) no concomitant pathology; (3) intraoperative administration of short-acting opioid drugs; (4) endotracheal extubation on awakening in the operating room; and (5) morphine as the parenteral, postoperative analgesic.

Results
Forty-six children (16 girls) fulfilled the inclusion criteria. Age and preoperative arterial oxygen saturation (SaO2) nadir, either individually (P = 0.023, P = 0.0003, respectively) or in combination (P = 0.00009), exhibited a significant correlation to the morphine dose required for analgesia. Four of these children, aged 26.5 +/- 13.2 months, with a preoperative SaO2 nadir of 70.3 +/- 12.9%, did not require any postoperative morphine for analgesia at all.

Conclusions
The authors speculate that the reduced morphine requirement for analgesia in children displaying oxygen desaturation associated with severe OSA may be related to their young age and to an up-regulation of central opioid receptors consequent to recurrent hypoxemia. In evaluating OSA in children, preoperative determination of the SaO2 nadir is important for predicting the postoperative opioid dosage required for analgesia.
Electroencephalographic Bicoherence Is Sensitive to Noxious Stimuli during Isoflurane or Sevoflurane Anesthesia
Authors: Hagihira Satoshi , Takashina Masaki , Mori Takahiko , Ueyama Hiroshi , Mashimo Takashi 
Published: March 2004

Background
The authors previously reported changes in electroencephalographic bicoherence during isoflurane anesthesia combined with epidural anesthesia. Here, they examined the influence of noxious stimuli on electroencephalographic bicoherence as well as on the Bispectral Index (BIS) and the 95% spectral edge frequency (SEF95).

Methods
The authors enrolled 48 elective abdominal surgery patients (aged 22-77 years; American Society of Anesthesiologists physical status I or II). Raw electroencephalographic signals as well as BIS and SEF95 were recorded on a computer using a BIS monitor (A-1050) and Bispectrum Analyzer (BSA) for BIS (the authors' original software). Using BSA for BIS, the authors evaluated the two peak heights of electroencephalographic bicoherence. Anesthesia was induced with 3 mg/kg thiopental and was maintained with, in air-oxygen, 1.0% isoflurane or 1.5% sevoflurane. After confirming the steady state, the authors recorded baseline values. In experiment 1, they administered 3 microg/kg fentanyl 5 min after incision and investigated the changes in electroencephalographic derivatives at 5 and 10 min after incision. In experiment 2, they administered a similar dose of fentanyl 5 min before incision and investigated the changes in electroencephalographic derivatives immediately before and 5 min after incision.

Results
In experiment 1, after incision, both peak heights of electroencephalographic bicoherence significantly decreased but returned to control values after fentanyl administration. By contrast, after incision, BIS and SEF95 showed individual variability. In experiment 2, although fentanyl itself did not affect all electroencephalographic derivatives before incision, the variables remained unchanged after incision.

Conclusion
Noxious stimuli decreased the peak heights of electroencephalographic bicoherence, an effect that was counteracted by fentanyl analgesia.
Perioperative Cardiorespiratory Complications in Adults with Mediastinal Mass
Authors: Béchard Philippe , Létourneau Louis , Lacasse Yves , Côté Dany , Bussières Jean S. 
Published: March 2004

Background
Patients with a mediastinal mass are at risk for cardiorespiratory complications in the perioperative period. The authors' objectives were to evaluate the incidence of life-threatening intraoperative cardiorespiratory and postoperative respiratory complications in adult patients and to study the usefulness of clinical signs and symptoms, radiologic evaluation, and pulmonary function tests in the determination of the perioperative risk.

Methods
The authors reviewed the investigation and treatment of adult patients presenting with anterior or middle mediastinal masses for surgery under anesthesia between January 1994 and July 2000.

Results
Ninety-eight patients underwent 105 anesthetic cases. The incidences of intraoperative cardiorespiratory and postoperative respiratory complications were 4 in 105 and 11 in 105, respectively. No collapse of the airways occurred during anesthesia. However, a high incidence of early postoperative life-threatening respiratory complications was observed (7 in 105). In a multivariate logistic regression analysis model, perioperative complications were predicted by the occurrence of cardiorespiratory signs and symptoms at the initial presentation (odds ratio [OR], 6.2) and the presence of combined obstructive and restrictive patterns (mixed pulmonary syndrome) on pulmonary function tests (OR, 3.9). Intraoperative complications were associated with pericardial effusion on computed tomography scan (OR, 19.8). Postoperative respiratory complications were related to tracheal compression of more than 50% on preoperative computed tomography scan evaluation (OR, 7.4) and mixed pulmonary syndrome on pulmonary function tests (OR, 15.1).

Conclusion
Obstruction of the airway in an adult with a mediastinal mass is a rare event in the intraoperative period. Nevertheless, caution should be observed for the occurrence of early postoperative life-threatening respiratory complications. Patient at high risk of perioperative complications can be identified by the occurrence of cardiopulmonary signs and symptoms at presentation, combined obstructive and restrictive pattern on pulmonary function tests, and computed tomography scan findings (tracheal compression > 50%, pericardial effusion, or both).
Preclinical Pharmacology of GW280430A (AV430A) in the Rhesus Monkey and in the Cat
Authors: Savarese John J. , Belmont Matthew R. , Hashim Mir A. , Mook Robert A. , Boros Eric E. , Samano Vicente , Patel Sanjay S. , Feldman Paul L. , Schultz Jan-Ake I. , McNulty Michael , Spitzer Timothy , Cohn Douglas L. , Morgan Philip , Wastila William B. 
Published: March 2004

Background
No replacement for succinylcholine is yet available. GW280430A (AV430A) is a representative of a new class of nondepolarizing neuromuscular blocking drugs called asymmetric mixed-onium chlorofumarates. It undergoes rapid degradation in plasma by chemical hydrolysis and inactivation by cysteine adduction, resulting in a very short duration of effect. The neuromuscular, cardiovascular, and autonomic pharmacology of GW280430A is compared herein with that of mivacurium.

Methods
Adult male rhesus monkeys and adult male cats were anesthetized with nitrous oxide-oxygen-halothane and chloralose-pentobarbital, respectively. The neuromuscular blocking properties of GW280430A and mivacurium were compared at a stimulation rate of 0.15 Hz in the extensor digitorum of the foot (monkey) and the tibialis anterior (cat). Sympathetic responses were assayed in the cat in the nictitating membrane preparation, and vagal effects were evaluated in the cat via observation of bradycardic responses after stimulation of the cervical right vagus nerve.

Results
GW280430A and mivacurium were equipotent in the monkey (ED95 was 0.06 mg/kg in each case). GW280430A was half as potent as mivacurium in the cat. The total duration of action of GW280430A was less than half that of mivacurium in the monkey; recovery slopes were more than twice as rapid. The 25-75% recovery index of GW280430A did not vary significantly after various bolus doses or infusions, averaging 1.4-1.8 min in the monkey, significantly shorter than the same time interval (4.8-5.7 min) for mivacurium. Dose ratios for autonomic versus neuromuscular blocking properties in the cat were greater than 25 for both GW280430A and mivacurium. The ratio ED Hist:ED95 Neuromuscular Block in the monkey was significantly greater (approximately 53 vs. 13) for GW280430A, indicating approximately four times less relative prominence of the side effects of skin flushing and decrease of blood pressure, which are associated with release of histamine.

Conclusions
These experiments show a much shorter neuromuscular blocking effect and much-reduced side effects in the case of GW280430A vis-à-vis mivacurium. These results, together with the novel chemical degradation of GW280430A, suggest further evaluation in human subjects.
Cardiopulmonary Effects of the Novel Neuromuscular Blocking Drug GW280430A (AV430A) in Dogs
Authors: Heerdt Paul M. , Kang Richard , The’ Andrew , Hashim Mir , Mook Robert J. , Savarese John J. 
Published: March 2004

Background
This investigation determined the cardiopulmonary side effects of a novel nondepolarizing neuromuscular blocking drug with an ultrashort duration of action in anesthetized male beagles.

Methods
The ED95 for GW280430A was first determined in four animals. These data were then used to guide bolus dosing in multiples of ED95 in six dogs instrumented for hemodynamic measurements as well as inspiratory pressure and pulmonary compliance. Cardiopulmonary data were compared before and after the conclusion of a 60- to 90-min GW280430A infusion and in response to subsequent incremental bolus dosing starting with 3.125 x ED95. An adverse response was regarded as an alteration of 10% or greater in any variable. Arterial blood was obtained for histamine analysis before and 1 min after each dose.

Results
The ED95 of GW280430A was 0.064 +/- 0.01 mg/kg, and stable neuromuscular blockade was maintained with infusion of 0.012 +/- 0.002 mg.kg(-1).min(-1). With the exception of a late 14% increase in heart rate, there were no cardiopulmonary changes during infusion. Bolus dosing produced no cardiopulmonary change until a decrease in mean arterial pressure was elicited in four of six dogs at 25 x ED95. This response was modest, transient, and associated with a concomitant increase in plasma histamine concentration. There were no accompanying changes indicative of direct myocardial depression, pulmonary vasoconstriction, or bronchospasm.

Conclusions
These data indicate that GW280430 does not produce demonstrable cardiovascular effects in the anesthetized dog until doses far in excess of the ED95 are administered as a bolus.
Acute Hyperinsulinemia Restrains Endotoxin-induced Systemic Inflammatory Response
Authors: Brix-Christensen Vibeke , Andersen Søren Kæseler , Andersen René , Mengel Annette , Dyhr Thomas , Andersen Niels Trolle , Larsson Anders , Schmitz Ole , Ørskov Hans , Tønnesen Else 
Published: March 2004

Background
Intensive insulin therapy in critically ill patients reduces morbidity and mortality. The current study elucidates whether acute hyperinsulinemia per se could attenuate the systemic cytokine response and improve neutrophil function during endotoxin (lipopolysaccharide)-induced systemic inflammation in a porcine model.

Methods
Pigs were anesthetized, mechanically ventilated, randomized into four groups, and followed for 570 min: group 1 (anesthesia solely, n = 10), group 2 (hyperinsulinemic euglycemic clamp [HEC], n = 9), group 3 (lipopolysaccharide, n = 10), group 4 (lipopolysaccharide-HEC, n = 9). Groups 3 and 4 were given a 180-min infusion of lipopolysaccharide (total, 10 microg/kg). Groups 2 and 4 were clamped (p-glucose: 5 mM/l, insulin 0.6 mU.kg(-1).min(-1)) throughout the study period. Changes in pulmonary and hemodynamic function, circulating cytokines, free fatty acids, glucagon, and neutrophil chemotaxis were monitored.

Results
Tumor necrosis factor alpha and interleukin 6 were significantly reduced in the lipopolysaccharide-HEC group compared with the lipopolysaccharide group (both P = 0.04). In the lipopolysaccharide-HEC group, the glucagon response was diminished compared with the lipopolysaccharide group (P < 0.05). Serum free fatty acid concentrations were decreased in animals exposed to HEC. Animals receiving lipopolysaccharide showed an increase in pulmonary pressure (P < 0.001), but otherwise, there were no major changes in pulmonary or hemodynamic function. Neutrophil function was impaired after lipopolysaccharide administration.

Conclusion
Hyperinsulinemia concomitant with normoglycemia reduces plasma concentrations of tumor necrosis factor alpha and the catabolic hormone glucagon in lipopolysaccharide-induced systemic inflammation in pigs. The finding strongly supports the role of insulin as an antiinflammatory hormone. Whether the effect to some extent operates via a reduced free fatty acid concentration is unsettled.
Influence of Fluid Infusion Associated with High-volume Blood Loss on Plasma Propofol Concentrations
Authors: Kurita Tadayoshi , Kazama Tomiei , Morita Koji , Fujii Shunsuke , Uraoka Masahiro , Takata Kotaro , Sato Shigehito 
Published: March 2004

Background
It is common clinical practice to use fluid infusion to manage high-volume blood loss until a blood transfusion is performed. The authors investigated the influence of fluid infusion associated with blood loss on the pseudo-steady state propofol concentration.

Methods
Twenty-seven swine were assigned to a lactated Ringer's solution group, a hydroxyethyl starch group, or a threefold lactated Ringer's solution group (n = 9 in each group). After 180 min of steady state infusion of propofol at a rate of 2 mg.kg(-1).h(-1), hemorrhage and infusion were induced by stepwise bleeding followed by fluid infusion every 30 min. In each of the first two steps, 400 ml blood was collected; thereafter, 200 ml was collected at each step. Just after each bleeding step, fluid infusion was rapidly performed using a volume of lactated Ringer's solution or hydroxyethyl starch equivalent to the blood withdrawn, or a threefold volume of lactated Ringer's solution. Hemodynamic parameters and the plasma propofol concentration were recorded at each step.

Results
Although the plasma propofol concentration in the lactated Ringer's solution group increased with hemorrhage and infusion, it decreased in both the hydroxyethyl starch and the threefold lactated Ringer's solution groups. The propofol concentration in the hydroxyethyl starch group could be expressed by the following equation: Plasma Propofol Concentration Decrease (%) = 0.80 x Hematocrit Decrease (%) (r2 = 0.83, P < 0.0001).

Conclusions
When high-volume blood loss is managed by isovolemic hemodilution, the plasma propofol concentration during continuous propofol infusion decreases linearly with the hematocrit decrease.
Hemorrhage during Isoflurane–Nitrous Oxide Anesthesia
Authors: Höhne Claudia , Vogler Pia , Frerking Ilka , Francis Roland C. E. , Swenson Erik R. , Kaczmarczyk Gabriele , Boemke Willehad 
Published: March 2004

Background
The objective of this study was to determine whether endothelin-A receptor blockade (ETAB) impairs hemodynamic and hormonal regulation compared with controls and angiotensin II receptor blockade (AT1B) during hypotensive hemorrhage in dogs under isoflurane-nitrous oxide anesthesia.

Methods
Six dogs were studied in four protocols: (1) control experiments (controls); (2) ETA blockade using ABT-627 (ETAB); (3) AT1 blockade using losartan (AT1B); and (4) combined AT1B and ETAB (AT1B + ETAB). After a 30-min awake period, isoflurane-nitrous oxide anesthesia was established (1.3 minimum anesthetic concentration). After 60 min of anesthesia, 20 ml blood/kg body weight was withdrawn within 5 min, and the dogs were observed for another hour. Thereafter, the blood was retransfused, and the dogs were observed for a final hour.

Results
Anesthesia: Cardiac output decreased in all protocols, whereas mean arterial pressure decreased more in AT1B and AT1B + ETAB than in controls and ETAB. Hemorrhage: After 60 min, cardiac output had decreased less in controls than in all other protocols. Mean arterial pressure decreased more during ETAB than in controls, but most severely during AT1B and AT1B + ETAB. Angiotensin II increased further only in controls and ETAB, whereas vasopressin and catecholamines increased similarly in all protocols. Retransfusion: Mean arterial pressure remained below controls in all protocols but was lowest when the AT1 receptor was blocked. Cardiac output fully recovered in all but the ETAB protocol.

Conclusions
ETAB impairs long-term hemodynamic regulation after hemorrhage and retransfusion during anesthesia despite an activation of vasoconstrictive hormones. This suggests that endothelins have a role in long-term cardiovascular regulation. AT1B impairs both short- and long-term blood pressure regulation during anesthesia and after hemorrhage.
Dexmedetomidine Enhances Analgesic Action of Nitrous Oxide
Authors: Dawson Cecilia , Ma Daqing , Chow Andre , Maze Mervyn 
Published: March 2004

Background
Nitrous oxide and dexmedetomidine are thought to mediate analgesia (antinociception in a noncommunicative organism) via alpha 2B- and alpha 2A-adrenergic receptor subtypes within the spinal cord, respectively. Nitrous oxide and dexmedetomidine exert diametrically opposite effects on neuronal activity within the locus ceruleus, a pivotal site for modulation of analgesia. Because of these differences, the authors explored whether the two analgesics in combination would provide satisfactory analgesia.

Methods
The analgesic effects of nitrous oxide and dexmedetomidine given both intraperitoneally and intrathecally were evaluated using the tail-flick latency test in rats. For investigation of the interaction, rats were pretreated with dexmedetomidine, either intraperitoneally or intrathecally, immediately before nitrous oxide exposure such that peak antinociceptive effects of each drug coincided. For assessment of the effect on tolerance, dexmedetomidine was administered as tolerance to nitrous oxide developed. Expression of c-Fos was used to assess neuronal activity in the locus ceruleus.

Results
Nitrous oxide and dexmedetomidine increased tail-flick latency with an ED50 (mean +/- SEM) of 55.0 +/- 2.2% atm for nitrous oxide, 27.6 +/- 5.1 for microg/kg intraperitoneal dexmedetomidine, and 2.9 +/- 0.1 microg for intrathecal dexmedetomidine. Combinations of systemically administered dexmedetomidine and nitrous oxide produced an additive analgesic interaction; however, neuraxially administered dexmedetomidine interacted synergistically with nitrous oxide. Tolerance to nitrous oxide was reversed by coadministration of dexmedetomidine. Prazosin, the alpha 1-/alpha 2B-adrenoceptor antagonist, attenuated the analgesic effect of nitrous oxide and prevented dexmedetomidine-induced reversal of tolerance to nitrous oxide. Nitrous oxide-induced increase of neuronal activity in the locus ceruleus was reversed by dexmedetomidine.

Conclusion
The synergistic analgesic interaction between nitrous oxide and dexmedetomidine within the spinal cord is obscured by a supraspinal antagonism when dexmedetomidine is administered systemically in the pretolerant state. After tolerance to nitrous oxide develops, supraspinal functional antagonism no longer obtains exposing the synergistic action at the level of the spinal cord, which expresses itself as a reversal of the tolerant state. The authors speculate that the addition of dexmedetomidine to nitrous oxide is likely to provide enhanced and more durable analgesia in settings in which nitrous oxide is currently used alone (e.g., labor and dental surgery).
Can Ropivacaine and Levobupivacaine Be Used as Test Doses during Regional Anesthesia?
Authors: Owen Medge D. , Gautier Philippe , Hood David D. 
Published: March 2004

Background
Lower systemic toxicity reported with ropivacaine and levobupivacaine may produce less reliable recognition of inadvertent intravenous injection during regional anesthesia. This study was undertaken to determine whether ropivacaine and levobupivacaine are suitable for use as intravenous test doses by evaluating central nervous system (CNS) symptoms after intravenous bolus injection.

Methods
Institutional approval and informed consent were granted for the study. One hundred twenty patients scheduled to undergo elective surgery were randomly assigned to receive 5 ml intravenous saline, 100 mg lidocaine, 25 mg ropivacaine, or 25 mg levobupivacaine before anesthesia. Patients reported CNS symptoms after injection and were monitored for hemodynamic change.

Results
Intravenous ropivacaine or levobupivacaine produced CNS symptoms in only 52% and 57% of patients, respectively, compared with 87% of patients after lidocaine (P < 0.02). Despite preparatory instruction, many patients receiving ropivacaine or levobupivacaine did not spontaneously volunteer symptoms because they were subtle and admitted symptoms only after in-depth questioning by the investigator.

Conclusions
Plain ropivacaine and levobupivacaine (25 mg) solutions are unsuitable for use as intravenous test doses during regional anesthesia because CNS symptoms are insufficient. When using ropivacaine or levobupivacaine for regional anesthesia, for test dose purposes, the authors recommend the addition of epinephrine to the local anesthetic solution or the use of a separate agent with more predictable CNS characteristics.
Intrathecal Anesthesia and Recovery from Radical Prostatectomy
Authors: Brown Daniel R. , Hofer Roger E. , Patterson David E. , Fronapfel Paul J. , Maxson Pamela M. , Narr Bradly J. , Eisenach John H. , Blute Michael L. , Schroeder Darrell R. , Warner David O. 
Published: March 2004

Background
Previous studies suggest that intraoperative anesthetic care may influence postoperative pain and recovery from surgery. The authors tested the hypothesis that the addition of intrathecal analgesia to general anesthesia would improve long-term functional status and decrease pain in patients undergoing radical retropubic prostatectomy.

Methods
One hundred patients received either general anesthesia supplemented with intravenous fentanyl or general anesthesia preceded by intrathecal administration of bupivacaine (15 mg), clonidine (75 microg), and morphine (0.2 mg). Patients and providers were masked to treatment assignment. All patients received multimodal pain management postoperatively. Primary outcomes included pain and functional status over the first 12 postoperative weeks.

Results
Patients receiving intrathecal analgesia required more intravenous fluids and vasopressors intraoperatively. Pain was well controlled throughout the study (mean numerical pain scores < 3 in both groups at all times studied). Intrathecal analgesia decreased pain and supplemental intravenous morphine use over the first postoperative day but increased the frequency of pruritus. Pain and functional status after discharge from the hospital did not differ between groups. Intrathecal analgesia significantly decreased the duration of hospital stay (from 2.8 +/- 2.0 to 2.1 +/- 0.5 days; P < 0.01) as a result of five patients in the control group who stayed in the hospital more than 3 days.

Conclusions
The benefits of improved immediate analgesia and decreased morphine requirements resulting from intrathecal analgesia must be weighed against factors such as pruritus, increased intraoperative requirement for fluids and vasopressors, and resources needed to implement this modality. Further studies are needed to determine the significance of the decrease in duration of hospital stay.