bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex Differences in Morphine-induced Ventilatory Depression Reside within the Peripheral Chemoreflex Loop
Authors: Sarton Elise , Teppema Luc , Dahan Albert 
Published: November 2003

Background
This study gathers information in humans on the sites of sex-related differences in ventilatory depression caused by the mu-opioid receptor agonist morphine.

Methods
Experiments were performed in healthy young men (n = 9) and women (n = 7). Dynamic ventilatory responses to square-wave changes in end-tidal carbon dioxide tension (7.5-15 mmHg) and step decreases in end-tidal oxygen tension (step from 110 to 50 mmHg, duration of hypoxia 15 min) were obtained before and during morphine infusion (intravenous bolus dose 100 microg/kg, followed by 30 microg x kg(-1) x h(-1)). Each hypercapnic response was separated into a fast peripheral and slow central component, which yield central (Gc) and peripheral (Gp) carbon dioxide sensitivities. Values are mean +/- SD.

Results
In carbon dioxide studies in men, morphine reduced Gc from 1.61 +/- 0.33 to 1.23 +/- 0.12 l x min(-1) x mmHg(-1) (P < 0.05) without affecting Gp (control, 0.41 +/- 0.16 and morphine, 0.49 +/- 0.12 l x min(-1) x mmHg(-1), not significant). In carbon dioxide studies in women, morphine reduced Gc, from 1.51 +/- 0.74 to 1.17 +/- 0.52 l x min(-1) x mmHg(-1) (P < 0.05), and Gp, from 0.54 +/- 0.19 to 0.39 +/- 0.22 l x min(-1) x mmHg(-1) (P < 0.05). Morphine-induced changes in Gc were equal in men and women; changes in Gp were greater in women. In hypoxic studies, morphine depressed the hyperventilatory response at the initiation of hypoxia more in women than in men (0.54 +/- 0.23 vs. 0.26 +/- 0.34 l x min(-1) x %(-1), respectively; P < 0.05). The ventilatory response to sustained hypoxia (i/e., 15 min) did not differ between men and women.

Conclusions
The data indicate the existence of sex differences in morphine-induced depression of responses mediated via the peripheral chemoreflex pathway, with more depression in women, but not of responses mediated via the central chemoreflex pathway. In men and women, morphine did not change the translation of the initial hyperventilatory response to short-term hypoxia into the secondary decrease in inspired minute ventilation (Vi) caused by sustained hypoxia.
Effect of Sevoflurane and Desflurane on the Myogenic Constriction and Flow-induced Dilation in Rat Coronary Arterioles
Authors: Park Kyung W. , Dai Hai B. , Lowenstein Edward , Sellke Frank W. 
Published: November 2003

Background
Determinants of myocardial blood flow distribution include metabolic, myogenic, endothelial, and neurohumoral control mechanisms. The authors studied the effect of sevoflurane and desflurane on the myogenic and endothelial mechanisms.

Methods
Wistar rat subepicardial microvessels, approximately 100 microm in diameter, were monitored for diameter changes in vitro using a video detection system. Myogenic vasomotion was studied by varying the intraluminal pressure from 10 mmHg to 120 mmHg. Flow-induced, endothelium-dependent dilation was evaluated in U46619-preconstricted vessels by varying the pressure gradient across the isolated vessel from 10 mmHg to 80 mmHg, while maintaining the midpoint luminal pressure constant at 40 mmHg to avoid myogenic effects. Myogenic and flow-induced vasomotion both were studied in the presence of sevoflurane, 1 or 2 minimum alveolar concentration (MAC) (MAC is a unit of inhalational anesthetic potency), desflurane, 1 or 2 MAC, or no anesthetic (control).

Results
Myogenic constriction was shown above intraluminal pressures of 70 mmHg. Myogenic constriction was unchanged by sevoflurane, 1 MAC (P = 0.24), but was mildly enhanced by sevoflurane, 2 MAC (P < 0.05), or desflurane, 1 (P < 0.05) or 2 MAC (P < 0.01). Flow-induced dilation was shown over the pressure gradient range of 10-80 mmHg. Flow-induced dilation was not altered significantly by sevoflurane, 1 or 2 MAC (P > 0.3 each), but was significantly attenuated by desflurane, 1 or 2 MAC (P < 0.001 each).

Conclusions
Sevoflurane maintains myogenic and endothelial determinants of myocardial blood flow distribution. Conversely, desflurane attenuates endothelium-dependent flow-induced dilation while mildly enhancing myogenic constriction.
Extreme, Progressive Isovolemic Hemodilution with 5% Human Albumin, PentaLyte, or Hextend Does Not Cause Hepatic Ischemia or Histologic Injury in Rabbits
Authors: Nielsen Vance G. , Baird Manuel S. , Brix Amy E. , Matalon Sadis 
Published: November 2003

Background
Physicians and their patients are greatly concerned about perioperative blood administration. Although isovolemic hemodilution is utilized to decrease the incidence of transfusion, it is unclear at what degree of hemodilution hepatoenteric ischemia and injury occurs. The authors hypothesized that hepatic ischemia, systemic ischemia, and tissue injury would occur during hemodilution in rabbits, and that the severity of ischemia and injury may be dependent on the fluid administered.

Methods
Rabbits anesthetized with isoflurane were assigned randomly to a sham-operated group (n = 8) or groups that underwent four isovolemic hemodilutions (25% of the blood volume removed at hourly intervals), with blood replaced with one of three solutions: balanced electrolyte solutions containing 6% pentastarch (n = 8), 6% hetastarch (n = 9), or 5% human albumin in normal saline (n = 8). Arterial ketone body ratio and plasma lactate, respectively, served as measures of hepatic and systemic ischemia. Gastric, duodenal, and hepatic histologic injury was assessed post mortem.

Results
Hemodilution from a baseline hematocrit of about 33% to about 8% (third hemodilution) with all three colloids did not result in a significant increase in plasma lactate concentration or decrease in arterial ketone body ratio. At a hematocrit of about 5% (fourth hemodilution), the hetastarch group had a significantly (P < 0.05) greater plasma lactate concentration than the sham-operated and 5% human albumin groups. There were no significant differences in arterial ketone body ratio or histologic injury between the groups.

Conclusions
Isovolemic hemodilution (approximately 5% hematocrit) with albumin, pentastarch, or hetastarch solutions does not result in significant hepatic ischemia or injury assessed by histology.
Effects of Sevoflurane on Regional Myocardial Blood Flow Distribution
Authors: Kitahata Hiroshi , Kawahito Shinji , Nozaki Junpei , Kimura Hideyuki , Tanaka Katsuya , Kitagawa Tetsuya , Oshita Shuzo 
Published: November 2003

Background
Using myocardial contrast echocardiography, the authors tried to determine whether sevoflurane causes myocardial blood maldistribution in humans and dogs.

Methods
In animal experiments, 15 mongrel dogs were organized into dipyridamole (n = 6) and sevoflurane (n = 9) groups. Sonicated albumin was infused into the left main coronary artery. The peak gray level corrected for background was analyzed at the following intervals: (1) at baseline, (2) after stenosis of the left circumflex coronary artery (blood flow reduced by 40%), (3) after administration of dipyridamole (1 mg/kg given intravenously) or sevoflurane (1 minimum alveolar concentration) during stenosis, and (4) after phenylephrine during stenosis and administration of dipyridamole or sevoflurane. In human studies, nine patients undergoing coronary artery bypass grafting were studied. During partial extracorporeal circulation, the peak gray level was analyzed before and 20 min after sevoflurane (1 minimum alveolar concentration).

Results
In animal experiments, dipyridamole decreased significantly the inner:outer ratio of the peak gray level in the ischemic area and the ischemic:normal ratio of the peak gray level. After arterial pressure was restored with phenylephrine, neither the inner:outer ratio nor the ischemic:normal ratio improved. In contrast, after sevoflurane administration, the inner:outer ratio and the ischemic:normal ratio remained unchanged, but these increased with phenylephrine. In human studies, sevoflurane did not change the inner:outer ratio in the area supplied by the most stenotic coronary artery.

Conclusion
These results suggest that dipyridamole, a potent coronary vasodilator, produces maldistribution of coronary blood flow in our dog models, whereas sevoflurane does not do this in animal or human studies.
Propofol Prevents Peroxide-induced Inhibition of Glutamate Transport in Cultured Astrocytes
Authors: Sitar Sandra M. , Hanifi-Moghaddam Pejman , Gelb Adrian , Cechetto David F. , Siushansian Ramin , Wilson John X. 
Published: November 2003

Background
Glutamate transporters located in the plasma membrane of cerebral astrocytes take up excitatory neurotransmitters from the synaptic cleft. In diseases characterized by oxidative stress, the extracellular glutamate concentration increases and contributes to neuronal death. The authors wanted to determine whether propofol defends brain cells against oxidant-induced changes in their transport of glutamate.

Methods
Primary cultures of rat cerebral astrocytes were exposed to tert-butyl hydroperoxide (1 mM) to serve as an in vitro model of oxidative stress. Astrocytes were incubated with propofol for 2 h and tert-butyl hydroperoxide was added for the final hour. Alternatively, astrocytes were incubated with tert-butyl hydroperoxide for 30 min and then with propofol for another 30 min. Control cells received drug vehicle rather than propofol. The rate of uptake of glutamate, the efflux of the nonmetabolizable analog D-aspartate, and the intracellular concentration of the endogenous antioxidant glutathione were measured.

Results
Tert-butyl hydroperoxide decreased the glutathione concentration and inhibited glutamate uptake but had a negligible effect on D-aspartate efflux. At clinically relevant concentrations, propofol did not affect the glutathione concentration but did prevent the effect of tert-butyl hydroperoxide on glutamate transport. Furthermore, the addition of propofol after tert-butyl hydroperoxide reversed the inhibition of glutamate uptake.

Conclusions
Propofol prevents and reverses the inhibition of excitatory amino acid uptake in astrocytes exposed to tert-butyl hydroperoxide. The ability of propofol to defend against peroxide-induced inhibition of glutamate clearance may prevent the pathologic increase in extracellular glutamate at synapses, and thus delay or prevent the onset of excitotoxic neuronal death.
Oral Ketamine and Transdermal Nitroglycerin as Analgesic Adjuvants to Oral Morphine Therapy for Cancer Pain Management
Authors: Lauretti Gabriela R. , Lima Izabel C. P. R. , Reis Marlene P. , Prado Wiliam A. , Pereira Newton L. 
Published: November 2003

Background
Guidelines for cancer pain management include nonsteroidal antiinflammatory drugs with opioids administered in a time-contingent manner. This study was designed to evaluate the role of oral ketamine or transdermal nitroglycerin polymer, a nitric oxide donor, as coadjuvants to oral morphine in cancer pain therapy.

Methods
After institutional approval and informed patient consent were obtained, 60 patients with cancer pain were randomized to one of four groups (n = 15) and studied prospectively to evaluate analgesia and any adverse effects. A visual analog scale that consisted of a 10-cm line with 0 representing "no pain at all" and 10 representing "the worst possible pain" was introduced. All patients were regularly taking oral amitriptyline 50 mg at bedtime. The morphine regimen was adjusted individually to a maximal oral dose of 80-90 mg/day to keep the visual analog scale score less than 4. When patients reported pain (visual analog scale of 4 or more), despite taking 80-90 mg oral morphine daily, the test drug was added as follows: the control group (CG) received an additional 20 mg oral morphine (10 mg at 12-h intervals); the nitroglycerin group (NG) received a 5-mg nitroglycerin patch daily; the ketamine group (KG) received 0.5 mg/kg oral ketamine at 12-h intervals; and the dipyrone group (DG) received 500 mg oral dipyrone at 6-h intervals. Patients were free to manipulate their daily morphine consumption when the test drug was introduced to keep their visual analog scale score less than 4.

Results
The groups were similar with respect to demographic data and visual analog scale pain scores before treatment. The visual analog scale scores after the test drug was introduced were similar among the groups. The daily consumption of oral morphine was as follows: on day 15: CG = DG = NG (P > 0.05), CG > KG (P = 0.036); on day 20: CG > NG = KG (P < 0.02) (CG > KG, P < 0.005; CG > NG, P < 0.02), DG > KG (P < 0.05); on day 30: CG = DG > KG = NG (P < 0.05). Patients in the CG and DG groups reported somnolence, but patients in the NG and KG groups did not.

Conclusions
Low-dose ketamine and transdermal nitroglycerin were effective coadjuvant analgesics. In conjunction with their opioid tolerance-sparing function, joint delivery of ketamine or nitric oxide donors with opiates may be of significant benefit in cancer pain management.
Determination of the Potency of Remifentanil Compared with Alfentanil Using Ventilatory Depression as the Measure of Opioid Effect
Authors: Glass Peter S. A. , Iselin-Chaves Irene A. , Goodman David , Delong Elizabeth , Hermann David J. 
Published: November 2003

Background
Remifentanil is a new opioid with properties similar to other mu-specific agonists. To establish its pharmacologic profile relative to other known opioids, it is important to determine its potency. This study investigated the relative potency of remifentanil compared with alfentanil.

Methods
Thirty young healthy males were administered double-blind remifentanil or alfentanil intravenously for 180 min using a computer-assisted continuous infusion device. Depression of ventilation was assessed by the minute ventilatory response to 7.5% CO2 administered via a "bag in the box" system. The target concentration of the study drug was adjusted to obtain 40-70% depression of baseline minute ventilation. Multiple blood samples were obtained during and following the infusion. The concentration-effect relationship of each drug was modeled, and the concentration needed to provide a 50% depression of ventilation (EC50) was determined.

Results
Only 11 subjects in each drug group completed the study; however, there were sufficient data in 28 volunteers to model their EC50 values. The EC50 (mean and 95% confidence interval) for depression of minute ventilation with remifentanil was 1.17 (0.85-1.49) ng/ml and the EC50 for alfentanil was 49.4 (32.4-66.5) ng/ml.

Conclusion
Based on depression of the minute ventilatory response to 7.5% CO2, remifentanil is approximately 40 (26-65) times more potent than alfentanil when remifentanil and alfentanil whole-blood concentrations are compared. As alfentanil is usually measured as a plasma concentration, remifentanil is approximately 70 (41-104) times more potent than alfentanil when remifentanil whole-blood concentration is compared with alfentanil plasma concentration. This information should be used when performing comparative studies between remifentanil and other opioids.
Propofol Requirement Is Decreased in Patients with Large Supratentorial Brain Tumor
Authors: Chan Matthew T. V. , Gin Tony , Poon Wai S. 
Published: November 2003

Background
The anesthetic requirement is decreased in animals with head injury, but there are no data regarding the effect of intracranial tumor on the potency for intravenous anesthetics. The authors compared the quantal dose-response curves for propofol in patients having large (> or = 30 mm, mass effect) brain tumor with those having smaller (< 30 mm) lesions and with control patients undergoing noncranial surgery.

Methods
Sixty patients in each group were randomly assigned to receive one of the six doses of propofol (0.5, 0.7, 1.0, 1.3, 1.8, or 2.5 mg/kg) over 10 s. Two minutes after drug administration, patients were asked to open their eyes as a test for response to verbal command. Patients who failed to respond were given a 10-s, 50-Hz, 80-mA transcutaneous tetanic electrical current to the ulnar nerve as a test for response to painful stimulus. Purposeful movement indicated positive response. Log dose-response curves for loss of response to verbal command and tetanic stimulus were calculated after logit transformation.

Results
The median effective doses (ED50s; 95% confidence interval) for suppressing response to verbal command and tetanic stimulus were 0.75 (0.65-0.86) mg/kg and 1.28 (1.11-1.49) mg/kg, respectively, in patients with large brain tumor. These values were significantly less than the corresponding ED50s in patients with small tumor, 1.01 (0.88-1.15) mg/kg and 1.76 (1.51-2.07) mg/kg, or healthy control subjects, 0.98 (0.86-1.12) mg/kg and 1.89 (1.62-2.23) mg/kg.

Conclusions
The doses of propofol required to suppress response to verbal command and tetanic stimulus were 23% less and 32% less in patients with large brain tumor compared with control subjects. Small tumor did not affect potency of propofol.
The Independent Effect of Propofol Anesthesia on Whole Body Protein Metabolism in Humans
Authors: Schricker Thomas , Klubien Kristine , Carli Franco 
Published: November 2003

Background
The purpose of this study was to examine the effect of general anesthesia with propofol in the absence of surgical stimulation on whole body protein metabolism.

Methods
Six unpremedicated patients were studied. General anesthesia included propofol (120 microg x kg(-1) x min(-1)), vecuronium bromide, and oxygen-enriched air. Changes in protein breakdown, protein oxidation, and synthesis were measured by an isotope dilution technique using a constant infusion of the stable isotope tracer L-[1-13C]leucine (0.008 mg x kg(-1) x min(-1)) before and during 100 min of propofol anesthesia. The plasma concentrations of glucose, lactate, non-esterified fatty acids, and cortisol were measured before and during anesthesia.

Results
An isotopic steady state of plasma [1-13C]alpha-ketoisocaproate (taken to represent the intracellular leucine precursor pool enrichment for protein synthesis) and expired 13C-carbon dioxide were obtained before and during propofol infusion. Whole body protein breakdown decreased during propofol anesthesia by 6% (P < 0.05), whereas protein synthesis and oxidation did not change significantly. Plasma concentration of cortisol decreased after 90 min of propofol anesthesia (P < 0.05). No significant changes of plasma concentrations of glucose, lactate, and non-esterified fatty acids occurred during propofol administration.

Conclusions
Propofol anesthesia did not significantly affect whole body protein synthesis and oxidation but caused a small, although significant, decrease in whole body protein breakdown, possibly mediated through the suppression of plasma cortisol concentration.
A Prospective Randomized Comparison of Three Blood Conservation Strategies for Radical Prostatectomy
Authors: Monk Terri G. , Goodnough Lawrence T. , Brecher Mark E. , Colberg John W. , Andriole Gerald L. , Catalona William J. 
Published: November 2003

Background
Preoperative autologous blood donation is a standard of care for elective surgical procedures requiring transfusion. The authors evaluated the efficacy of alternative blood-conservation strategies including preoperative recombinant human erythropoietin (rHuEPO) therapy and acute normovolemic hemodilution (ANH) in radical retropubic prostatectomy patients.

Methods
Seventy-nine patients were prospectively randomized to preoperative autologous donation (3 U autologous blood); rHuEPO plus ANH (preoperative subcutaneous administration of 600 U/kg rHuEPO at 21 and 14 days before surgery and 300 U/kg on day of surgery followed by ANH in the operating room); or ANH (blinded, placebo injections per the rHuEPO regimen listed previously). Transfusion outcomes, perioperative hematocrit levels, postoperative outcomes, and blood-conservation costs were compared among the three groups.

Results
Baseline hematocrit levels were similar in all groups (43%+/-2%). On the day of surgery hematocrit decreased to 34% +/-4% in the preoperative autologous donation group (P < 0.001), increased to 47%+/-2% in the rHuEPO plus ANH group (P < 0.001), and remained unchanged at 43%+/-2% in the ANH group. Allogeneic blood exposure was similar in all groups. The rHuEPO plus ANH group had significantly higher hematocrit levels compared with the other groups throughout the hospitalization (P < 0.001). Average transfusion costs were significantly lower for ANH ($194+/-$192) compared with preoperative autologous donation ($690+/-$128; P < 0.001) or rHuEPO plus ANH ($1,393+/-$204, P < 0.001).

Conclusions
All three blood-conservation strategies resulted in similar allogeneic blood exposure rates, but ANH was the least costly technique. Preoperative rHuEPO plus ANH prevented postoperative anemia but resulted in the highest transfusion costs.
Management of Bladder Function after Outpatient Surgery
Authors: Pavlin Janet D. , Pavlin Edward G. , Fitzgibbon Dermot R. , Koerschgen Meagan E. , Plitt Terryn M. 
Published: November 2003

Background
This study was designed to test a treatment algorithm for management of bladder function after outpatient general or local anesthesia.

Methods
Three hundred twenty-four outpatients, stratified into risk categories for urinary retention, were studied. Patients in category 1 were low-risk patients (n = 227) having non-pelvic surgery and randomly assigned to receive 10 ml/kg or 2 ml/kg of intravenous fluid intraoperatively. They were discharged when otherwise ready, without being required to void. Patients in category 2 (n = 40), also presumed to be low risk, had gynecologic surgery. High-risk patients included 31 patients having hernia or anal surgery (category 3), and 31 patients with a history of retention (category 4). Bladder volumes were monitored by ultrasound in those in categories 2-4, and patients were required to void (or be catheterized) before discharge. The incidence of retention and urinary tract symptoms after surgery were determined for all categories.

Result
Urinary retention affected 0.5% of category 1 patients and none of category 2 patients. Median time to void after discharge was 75 min (interquartile range 120) in category 1 patients (n = 27) discharged without voiding. Fluids administered did not alter incidence of retention or time to void. Retention occurred in 5% of high-risk patients before discharge and recurred in 25% after discharge.

Conclusion
In reliable patients at low risk for retention, voiding before discharge appears unnecessary. In high-risk patients, continued observation until the bladder is emptied is indicated to avoid prolonged overdistention of the bladder.