bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isoflurane Depresses Baroreflex Control of Heart Rate in Decerebrate Rats
Authors: Lee Jong S. , Morrow Don , Andresen Michael C. , Chang Kyoung S. K. 
Published: November 2003

Background
Isoflurane inhibits baroreflex control of heart rate (HR) by poorly understood mechanisms. The authors examined whether suprapontine central nervous system cardiovascular regulatory sites are required for anesthetic depression.

Methods
The effects of isoflurane (1 and 2 rat minimum alveolar concentration [MAC]) on the baroreflex control of HR were determined in sham intact and midcollicular-transected decerebrate rats. Intravenous phenylephrine (0.2-12 microg/kg) and nitroprusside (1-60 microg/kg) were used to measure HR responses to peak changes in mean arterial pressure (MAP). Sigmoidal logistic curve fits to HR-MAP data assessed baroreflex sensitivity (HR/MAP), HR range, lower and upper HR plateau, and MAP at half the HR range (BP50). Four groups (two brain intact and two decerebrate) were studied before, during, and after isoflurane. To assess sympathetic and vagal contributions to HR baroreflex, beta-adrenoceptor (1 mg/kg atenolol) or muscarinic (0.5 mg/kg methyl atropine) antagonists were administered systemically.

Results
Decerebration did not alter resting MAP and HR or baroreflex parameters. Isoflurane depressed baroreflex slope and HR range in brain-intact and decerebrate rats. In both groups, 1 MAC reduced HR range by depressing peak reflex tachycardia. Maximal reflex bradycardia during increases in blood pressure was relatively preserved. Atenolol during 1 MAC did not alter maximum reflex tachycardia. In contrast, atropine during 1 MAC fully blocked reflex bradycardia. Therefore, 1 MAC predominantly depresses sympathetic components of HR baroreflex. Isoflurane at 2 MAC depressed both HR plateaus and decreased BP50 in both groups.

Conclusions
Isoflurane depresses HR baroreflex control by actions that do not require suprapontine central nervous system sites. Isoflurane actions seem to inhibit HR baroreflex primarily by the sympathetic nervous system.
Patient-controlled Regional Analgesia (PCRA) at Home
Authors: Rawal Narinder , Allvin Renée , Axelsson Kjell , Hallén Jan , Ekbäck Gustav , Ohlsson Torbjörn , Amilon Anders 
Published: November 2003

Background
The aim of this randomized, double-blinded study was to compare the analgesic efficacy of bupivacaine versus ropivacaine brachial plexus analgesia after ambulatory hand surgery. An additional aim was to study the feasibility and safety of patient-controlled regional analgesia (PCRA) outside the hospital.

Methods
Sixty patients scheduled for ambulatory hand surgery underwent surgery with axillary plexus blockade. After surgery, the plexus catheter was connected to an elastomeric, disposable "homepump," containing 100 ml of either 0.125% bupivacaine or 0.125% ropivacaine. When patients experienced pain, they self-administered 10 ml of the study drug. Analgesic efficacy of PCRA was evaluated by self-assessment of pain intensity by visual analog scale (VAS) and verbal scale. Patients recorded adverse effects, technical problems, use of rescue analgesic tablets, and overall satisfaction. A follow-up telephone call was made the day after surgery.

Results
Visual analog scale scores decreased after each treatment in both groups, but there were no significant differences between the two drugs. One patient in each group took rescue dextropropoxyphene tablets. In both groups, 87% patients expressed their desire to have the same treatment again. On the day of surgery, significantly more patients were satisfied with ropivacaine PCRA. None of the patients had any signs or symptoms of local anesthetic toxicity or catheter infection.

Conclusions
This double-blinded study has demonstrated the feasibility of self-administration of local anesthetic to manage postoperative pain outside the hospital. Ropivacaine and bupivacaine provided effective analgesia, and patient satisfaction with PCRA was high. Patient selection, follow-up telephone call, and 24-h access to anesthesiology services are prerequisites for PCRA at home.
Dexamethasone Prolongs Local Analgesia after Subcutaneous Infiltration of Bupivacaine Microcapsules in Human Volunteers
Authors: Holte Kathrine , Werner Mads U. , Lacouture Peter G. , Kehlet Henrik 
Published: November 2003

Background
The addition of small amounts of dexamethasone to extended-release formulations of bupivacaine in microcapsules has been found to prolong local analgesia in experimental studies, but no clinical data are available.

Methods
In a double-blinded study, 12 healthy male volunteers were randomized to receive simultaneous subcutaneous injections of bupivacaine microcapsules with dexamethasone and bupivacaine microcapsules without dexamethasone in each calf. Local analgesia was assessed with a validated human pain model; main parameters evaluated were thermal, mechanical, and pain detection thresholds and suprathreshold responses to heat and mechanical stimulation. Measurements were performed every 2 h for the first 8 h and daily for the week after injection. Primary endpoints were evaluation of maximal analgesic effect, time of onset, and duration of analgesia. Summary measures (area under curve [AUC]) were considered best estimate of analgesia. Safety evaluations were performed daily for the first week and at 2 weeks, 6 weeks, and 6 months after injection.

Results
The addition of dexamethasone significantly prolonged local analgesia of bupivacaine microcapsules without influence on maximal analgesic effect. AUC in all thermal measurements and the sensory mechanical threshold were significantly increased between 1-7 days after drug injection in the group given dexamethasone compared with the group not given dexamethasone. No serious side effects were observed.

Conclusions
Addition of small amounts of dexamethasone to bupivacaine incorporated in microcapsules prolonged local analgesia compared with microcapsules with plain bupivacaine after subcutaneous administration in humans.
Dexamethasone in Combination with Dolasetron for Prophylaxis in the Ambulatory Setting
Authors: Coloma Margarita , White Paul F. , Markowitz Scott D. , Whitten Charles W. , Macaluso Amy R. , Berrisford Sally B. , Thornton Kevin C. 
Published: November 2003

Background
Postoperative nausea and vomiting after laparoscopic cholecystectomy remains a common problem despite routine antiemetic prophylaxis. Therefore, the authors investigated the effect of administering 4 mg intravenous dexamethasone as an adjunct to a 5-HT3 antagonist (12.5 mg intravenous dolasetron) with respect to patient outcome.

Methods
Outpatients (N = 140) were enrolled in this prospective, randomized, placebo-controlled, double-blind, institutional review board-approved protocol involving two antiemetic treatment groups. After induction of anesthesia, the control group received 1 ml intravenous saline, whereas the dexamethasone group received 4 mg intravenous dexamethasone. Both groups received 12.5 mg intravenous dolasetron at the time of gallbladder removal. A blinded observer recorded the recovery times, emetic episodes, rescue antiemetics, maximum nausea score, and time to achieve discharge criteria. Postdischarge side effects, as well as patient satisfaction and quality of recovery scores were assessed at 24 h after surgery.

Results
Although there was no difference in the incidence of postoperative nausea and vomiting in the early recovery period, the dexamethasone group had a shorter stay in the day-surgery unit (136 +/- 57 vs. 179 +/- 62 min) and more rapidly achieved discharge criteria (161 +/- 32 vs. 209 +/- 39 min). In addition, fewer patients in the dexamethasone group experienced nausea at home within 24 h after discharge (13 vs. 28%, P < 0.05). Finally, the dexamethasone group reported higher quality of recovery and patient satisfaction scores (P < 0.05).

Conclusions
The authors conclude that the adjunctive use of 4 mg intravenous dexamethasone shortened the time to achieve discharge criteria and improved the quality of recovery and patient satisfaction scores after laparoscopic cholecystectomy procedures in outpatients receiving prophylaxis with 12.5 mg intravenous dolasetron.
Effects of Surgical Levels of Propofol and Sevoflurane Anesthesia on Cerebral Blood Flow in Healthy Subjects Studied with Positron Emission Tomography
Authors: Kaisti Kaike K. , Metsähonkala Liisa , Teräs Mika , Oikonen Vesa , Aalto Sargo , Jääskeläinen Satu , Hinkka Susanna , Scheinin Harry 
Published: November 2003

Background
The authors report a positron emission tomography (PET) study on humans with parallel exploration of the dose-dependent effects of an intravenous (propofol) and a volatile (sevoflurane) anesthetic agent on regional cerebral blood flow (rCBF) using quantitative and relative (Statistical Parametric Mapping [SPM]) analysis.

Methods
Using H(2)(15)O, rCBF was assessed in 16 healthy (American Society of Anesthesiologists [ASA] physical status I) volunteers awake and at three escalating drug concentrations: 1, 1.5, and 2 MAC/EC(50), or specifically, at either 2, 3, and 4% end-tidal sevoflurane (n = 8), or 6, 9, and 12 microg/ml plasma concentration of propofol (n = 8). Rocuronium was used for muscle relaxation.

Results
Both drugs decreased the bispectral index and blood pressure dose-dependently. Comparison between adjacent levels showed that sevoflurane initially (0 vs. 1 MAC) reduced absolute rCBF by 36-53% in all areas, then (1 vs. 1.5 MAC) increased rCBF in the frontal cortex, thalamus, and cerebellum (7-16%), and finally (1.5 vs. 2 MAC) caused a dual effect with a 23% frontal reduction and a 38% cerebellar increase. In the propofol group, flow was also initially reduced by 62-70%, with minor further effects. In the SPM analysis of the "awake to 1 MAC/EC(50)" step, both anesthetic agents reduced relative rCBF in the cuneus, precuneus, posterior limbic system, and the thalamus or midbrain; additionally, propofol reduced relative rCBF in the parietal and frontal cortices.

Conclusions
Both anesthetic agents caused a global reduction of rCBF (propofol > sevoflurane) at the 1 MAC/EC(50) level. The effect was maintained at higher propofol concentrations, whereas 2 MAC sevoflurane caused noticeable flow redistribution. Despite the marked global changes, SPM analysis enabled detailed localization of regions with the greatest relative decreases.
Gastric Emptying of Water in Term Pregnancy
Authors: Wong Cynthia A. , Loffredi Mariann , Ganchiff Jeanne N. , Zhao Jia , Wang Zhao , Avram Michael J. 
Published: November 2003

Background
Healthy nonpregnant patients may ingest clear liquids until 2 h before induction of anesthesia without adversely affecting gastric volume. The purpose of this study was to compare gastric emptying in term, nonlaboring pregnant women after ingestion of 50 ml water (control) with that after ingestion of 300 ml water.

Methods
Gastric emptying was assessed in healthy, nonobese, term pregnant volunteers using both serial gastric ultrasound examinations (n = 9) and acetaminophen absorption (n = 11) in a crossover study design. After an overnight fast, volunteers ingested 1.5 g acetaminophen and 50 or 300 ml water (assigned in random order) on two occasions separated by at least 2 days. Serial gastric antrum cross-sectional areas were determined using gastric ultrasound imaging, and the half-time to gastric emptying was calculated. Serial plasma acetaminophen concentrations were measured. Areas under the plasma acetaminophen concentration versus time curve, peak concentrations, and time to peak concentration for 50- and 300-ml ingestions were compared.

Results
Gastric emptying half-time was significantly shorter after ingestion of 300 ml water than after ingestion of 50 ml (24 +/- 6 vs. 33 +/- 8 min). There were no differences in acetaminophen areas under the curve at 60, 90, or 120 min, or in acetaminophen peak concentration. Time to peak concentration of acetaminophen was significantly shorter after ingestion of 300 ml water than after ingestion of 50 ml (25 +/- 12 vs. 41 +/- 19 min).

Conclusions
Gastric emptying in healthy, term, nonobese, nonlaboring pregnant women is not delayed after ingestion of 300 ml water compared with that after an overnight fast.
N -Phenylethyl Amitriptyline in Rat Sciatic Nerve Blockade
Authors: Gerner Peter , Mujtaba Mustafa , Khan Mohammed , Sudoh Yukari , Vlassakov Kamen , Anthony Douglas C. , Wang Ging Kuo 
Published: November 2003

Background
The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na(+) channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties.

Methods
The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH(3) cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model.

Results
In vitro, N-phenylethyl amitriptyline at 10 microm elicits a greater block of Na(+) channels than amitriptyline (resting block of approximately 90% vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 +/- 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 +/- 3 min for lidocaine at 37 mm (n = 4; mean +/- SEM). However, there was evidence of neurotoxicity at 5 mm.

Conclusion
N-phenylethyl amitriptyline appears to have a narrow therapeutic range but is much more potent than lidocaine, providing a block duration several times longer than any clinically used local anesthetic. Further work in animal models of neuropathic pain will assess the potential use of this drug.
Acute Normovolemic Hemodilution Improves Oxygenation in Ischemic Flap Tissue
Authors: Schramm Sören , Wettstein Reto , Wessendorf Robert , Jakob Stephan M. , Banic Andrej , Erni Dominique 
Published: November 2003

Background
The flaps used in reconstructive surgery are prone to ischemia and hypoxia, which imply a considerable risk of wound-healing complications. During normovolemic hemodilution, the oxygenation may further deteriorate because of the lack of erythrocytes or improve because of increased microcirculatory blood flow. The aim of this study was to investigate the net effect of normovolemic hemodilution of various degrees on the microcirculation and oxygenation in ischemic flap tissue in adult minipigs.

Methods
A rectangular flap was raised in the middle of the epigastrium, consisting of an adequately perfused portion and a partly ischemic portion. The animals were randomly assigned to either the control group (n = 10) or the experimental group (n = 10) receiving graded normovolemic hemodilution with 6% hydroxyethyl starch 200-0.5.

Results
Normovolemic hemodilution caused a significant linear increase in total blood flow to the flap (measured by transit time flowmetry). In the ischemic flap tissue, both oxygen tension (measured by polarographic cells) and venous base excess were transiently improved during hemodilution (F = 4.79 and P = 0.019 for the regression of tissue oxygen tension on hemoglobin and hemoglobin squared, and F = 4.18 and P = 0.029 for base excess). The expected values reached a peak at hemoglobin concentrations of 9.1 and 8.5 g/dl, respectively. The measured values at this level of hemodilution were 17 +/- 10.7 mmHg (mean +/- SD) versus 7.6 +/- 1.9 mmHg (baseline) for oxygen tension and -1.7 +/- 3.4 versus -5.6 +/- 4.1 mM for venous base excess.

Conclusions
Our results suggest that the oxygenation in ischemic and hypoxic flap tissue may be improved by normovolemic hemodilution. The maximal benefit may be expected at a hemoglobin concentration at or slightly less than 9 g/dl.
Sevoflurane but Not Propofol Preserves Myocardial Function in Coronary Surgery Patients
Authors: De Hert Stefan G. , ten Broecke Pieter W. , Mertens Els , Van Sommeren Esther W. , De Blier Ivo G. , Stockman Bernard A. , Rodrigus Inez E. 
Published: November 2003

Background
Sevoflurane has been shown to protect against myocardial ischemia and reperfusion injury in animals. The present study investigated whether these effects were clinically relevant and would protect left ventricular (LV) function during coronary surgery.

Methods
Twenty coronary surgery patients were randomly assigned to receive either target-controlled infusion of propofol or inhalational anesthesia with sevoflurane. Except for this, anesthetic and surgical management was the same in all patients. A high-fidelity pressure catheter was positioned in the left ventricle and the left atrium. LV response to increased cardiac load, obtained by leg elevation, was assessed before and after cardiopulmonary bypass (CPB). Effects on contraction were evaluated by analysis of changes in dP/dt(max). Effects on relaxation were assessed by analysis of the load dependence of myocardial relaxation (R = slope of the relation between time constant tau of isovolumic relaxation and end-systolic pressure). Postoperative concentrations of cardiac troponin I were followed during 36 h.

Results
Before CPB, leg elevation slightly increased dP/dt(max) in the sevoflurane group (5 +/- 3%), whereas it remained unchanged in the propofol group (1 +/- 6%). After CPB, leg elevation resulted in a decrease in dP/dt(max) in the propofol group (-5 +/- 4%), whereas the response in the sevoflurane group was comparable to the response before CPB (5 +/- 4%). Load dependence of LV pressure fall (R) was similar in both groups before CPB. After CPB, R was increased in the propofol group but not in the sevoflurane group. Troponin I concentrations were significantly lower in the sevoflurane than in the propofol group.

Conclusions
Sevoflurane preserved LV function after CPB with less evidence of myocardial damage in the first 36 h postoperatively. These data suggest a cardioprotective effect of sevoflurane during coronary artery surgery.
Isoflurane-induced Facilitation of the Cardiac Sarcolemmal KATPChannel
Authors: Fujimoto Kazuhiro , Bosnjak Zeljko J. , Kwok Wai-Meng 
Published: November 2003

Background
Volatile anesthetics have cardioprotective effects that mimic ischemic preconditioning, including the involvement of adenosine triphosphate-sensitive potassium (K(ATP)) channels. However, evidence for a direct effect of volatile anesthetic on the K(ATP) channel is limited. In this study, the effects of isoflurane on the cardiac sarcolemmal K(ATP) channel were investigated.

Methods
Single ventricular myocytes were enzymatically isolated from guinea pig hearts. Whole cell and single-channel configurations, specifically the cell-attached and inside-out patch mode, of the patch clamp technique were used to monitor sarcolemmal K(ATP) channel current.

Results
In the cell-attached patch configuration, 2,4-dinitrophenol (150 microm) opened the sarcolemmal K(ATP) channel. Isoflurane (0.5 mm) further increased channel open probability and the number of active channels in the patch. In contrast, in the inside-out patch experiments, isoflurane had no significant effect on the K(ATP) channel activated by low ATP (0.2-0.5 mm). In addition, isoflurane had no effect on the K(ATP) channel when activated by adenosine diphosphate, adenosine + guanosine triphosphate, bimakalim, and 2,4-dinitrophenol under inside-out patch configurations. When K(ATP) current was monitored in the whole cell mode, isoflurane alone was unable to elicit channel opening. However, during sustained protein kinase C activation by 12,13-dibutyrate, isoflurane activated the K(ATP) current that was sensitive to glibenclamide. In contrast, isoflurane had no effect on the K(ATP) channel activated by 12,13-dibutyrate in a cell-free environment.

Conclusions
Isoflurane facilitated the opening of the sarcolemmal K(ATP) channel in the intact cell, but not in an excised, inside-out patch. The isoflurane effect was not due to a direct interaction with the K(ATP) channel protein, but required an intracellular component, likely including the translocation of specific protein kinase C isoforms. This suggests that the sarcolemmal K(ATP) channel may have a significant role in anesthetic-induced preconditioning.
The Influence of Mild Hypothermia on the Pharmacokinetics and Time Course of Action of Neostigmine in Anesthetized Volunteers
Authors: Heier Tom , Clough David , Wright Peter M. C. , Sharma Manohar L. , Sessler Daniel I. , Caldwell James E. 
Published: November 2003

Background
The pharmacokinetics, maximum effect, and time course of action of neostigmine were studied in seven human volunteers.

Methods
Each volunteer was studied twice, during both normothermia and hypothermia. Anesthesia was induced with 30 microg/kg alfentanil and 3 mg/kg propofol, and was maintained with 60-70% nitrous oxide and 0.7-0.9% isoflurane. The mechanical response of the adductor pollicis to train-of-four stimulation of the ulnar nerve was recorded, and central body temperature maintained stable at either less than 34.5 degrees C or greater than 36.5 degrees C by surface cooling or warming. Before neostigmine administration, a stable 5% twitch height was obtained by an infusion of vecuronium, and the infusion rate remained unchanged thereafter. Neostigmine, 70 microg/kg, was then infused over 2 min, and blood samples for estimation of neostigmine concentrations were collected at intervals for 240 min.

Results
With hypothermia, the central volume of distribution of neostigmine decreased by 38%, and onset time of maximum effect increased (4.6 vs. 5.6 min). Hypothermia did not change the clearance (696 ml/min), maximum effect, or duration of action of neostigmine.

Conclusions
The efficacy of neostigmine as an antagonist of vecuronium-induced neuromuscular block is not altered by mild hypothermia.
The Unexpected Difficult Airway and Lingual Tonsil Hyperplasia
Authors: Ovassapian Andranik , Glassenberg Raymond , Randel Gail I. , Klock Allan , Mesnick Paul S. , Klafta Jerome M. 
Published: November 2003

Background
An unexpected difficult intubation occurs because physical examination of the airway is imperfect in predicting it. Lingual tonsil hyperplasia (LTH) is one risk factor for an unanticipated failed intubation that is not detectable during a routine oropharyngeal examination. The authors attempted to determine the incidence of LTH in unanticipated failed intubation in patients subjected to general anesthesia.

Methods
Thirty-three patients with unanticipated failed intubation via direct laryngoscopy were subjected to airway examinations and fiberoptic pharyngoscopy to determine the cause(s) of failure. Mouth opening, mandibular subluxation, head extension, thyromental distance, and Mallampati airway class were recorded. Fiberoptic pharyngoscopy was then performed to evaluate the base of the tongue and valleculae.

Results
Of these 33 patients, none had an airway examination that suggested a difficult intubation. The lungs of 12 patients were difficult to ventilate by mask. In 15 patients, airway measurements were within normal limits with Mallampati class of I or II. Ten patients had a Mallampati class III airway, 6 associated with obesity and 5 with mildly limited head extension. Among the 5 morbidly obese patients, most of the weight was distributed on the lower trunk and body. The 3 remaining patients had a thyromental distance of 6 cm or less but otherwise had a normal airway examination. The only finding common to all 33 patients was LTH observed on fiberoptic pharyngoscopy.

Conclusion
Lingual tonsil hyperplasia can interfere with rigid laryngoscopic intubation and face mask ventilation. Routine physical examination of the airway will not identify its presence. The prevalence of LTH in adults and the extent of its contribution to failed intubation is unknown.