bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Nitric Oxide Synthase Decreases Anesthetic Requirements of Intravenous Anesthetics in Xenopus laevis
Authors: Tonner Peter H. , Scholz Jeans , Lamberz Lars , Schlamp Nikolas , Schulte am Esch Jochen 
Published: November 2003

Background
Acute inhibition of nitric oxide synthase (NOS) has been demonstrated to reduce the anesthetic requirements of volatile anesthetics. Recent data suggest that not only volatile but also intravenous anesthetic agents interact with nitric oxide (NO) metabolism. The aim of this study was to examine the effect of NOS inhibition by nitroG-L-arginine-methyl-ester (L-NAME) on the anesthetic action of the intravenous anesthetics thiopental, propofol, and ketamine.

Methods
The anesthetic potencies of thiopental, propofol, and ketamine were determined in Xenopus laevis tadpoles in the absence and presence of L-NAME. Anesthesia was defined as loss of righting reflex for 5 s. A nonlinear logistic regression curve was fitted to the data and half-maximal effective concentrations (EC50) were calculated. A second set of experiments was performed with different concentrations of L-NAME in the presence of the previously determined the EC50 of the intravenous anesthetics.

Results
The EC50s of the anesthetics thiopental, propofol, and ketamine were determined to be 25.5 +/- 2.0 microM, 1.9 +/- 0.1 microM, and 59.7 +/- 0.7 microM, respectively. The addition of L-NAME shifted the concentration-response curves to the left in a concentration-dependent manner. In the presence of 1 mM L-NAME, the EC50 of thiopental was reduced by 43%, the EC50 of propofol by 26%, and the EC50 of ketamine by 63%. The addition of D-NAME did not change the EC50 values of the three anesthetics. In the presence of L-arginine, the effect of L-NAME on the EC50 of thiopental was reversed. When administered by itself in a concentration range from 0.1 microM to 10 mM, L-NAME did not alter the behavior of the tadpoles.

Conclusions
The results of the present study show that acute inhibition of NOS by L-NAME results in reduced anesthetic requirements of the intravenous anesthetics thiopental, propofol, and ketamine. This interaction of acutely administered L-NAME and intravenous anesthetics indicates that the NO-cyclic guanosine 3',5'-monophosphate system is involved in mediating the anesthetic effect of these compounds.
Experimental Subarachnoid Hemorrhage in Rats
Authors: Cole Daniel J. , Nary Jeffrey C. , Reynolds Lowell W. , Patel Piyush M. , Drummond John C. 
Published: November 2003

Background
Hemodilution with diaspirin crosslinked hemoglobin (DCLHb) ameliorates occlusive cerebral ischemia. However, subarachnoid hemoglobin has been implicated as a cause of cerebral hypoperfusion. The effect of intravenous DCLHb on cerebral perfusion and neuronal death after experimental subarachnoid hemorrhage was evaluated.

Methods
Rats (n = 48) were anesthetized with isoflurane and subarachnoid hemorrhage was induced by injecting 0.3 ml of autologous blood into the cistema magna. Each animal received one of the following regimens: Control, no hematocrit manipulation; DCLHb, hematocrit concentration decreased to 30% with DCLHb; or Alb, hematocrit concentration decreased to 30% with human serum albumin. The experiments had two parts, A and B. In part A, after 20 min, cerebral blood flow (CBF) was assessed with 14C-iodoantipyrine autoradiography. In part B, after 96 h, in separate animals, the number of dead neurons was determined in predetermined coronal sections by hematoxylin and eosin staining.

Results
Cerebral blood flow was greater for the DCLHb group than for the control group; and CBF was greater for the Alb group than the other two groups (P < 0.05). In one section, CBF was 45.5 +/- 10.9 ml x 100 g(-1) x min(-1) (mean +/- SD) for the control group, 95.3 +/- 16.6 ml x 100 g(-1) x min(-1) for the DCLHb group, and 138.1 +/- 18.7 ml x 100 g(-1) x min(-1) for the Alb group. The number of dead neurons was less in the Alb group (611 +/- 84) than in the control group (1,097 +/- 211), and was less in the DCLHb group (305 +/- 38) than in the other two groups (P < 0.05).

Conclusions
These data support a hypothesis that hemodilution decreases hypoperfusion and neuronal death after subarachnoid hemorrhage. The data do not support the notion that intravascular molecular hemoglobin has an adverse effect on brain injury after subarachnoid hemorrhage.
Prophylactic Atenolol Reduces Postoperative Myocardial Ischemia
Authors: Wallace Arthur , Layug Beth , Tateo Ida , Li Juliet , Hollenberg Milton , Browner Warren , Miller David , Mangano Dennis T. 
Published: November 2003

Background
Perioperative myocardial ischemia occurs in 20-40% of patients at risk for cardiac complications and is associated with a ninefold increase in risk for perioperative cardiac death, myocardial infarction, or unstable angina, and a twofold long-term risk. Perioperative atenolol administration reduces the risk of death for as long as 2 yr after surgery. This randomized, placebo-controlled, double-blinded trial tested the hypothesis that perioperative atenolol administration reduces the incidence and severity of perioperative myocardial ischemia, potentially explaining the observed reduction in the risk for death.

Methods
Two-hundred patients with, or at risk for, coronary artery disease were randomized to two study groups (atenolol and placebo). Monitoring included a preoperative history and physical examination and daily assessment of any adverse events. Twelve-lead electrocardiography (ECG), three-lead Holter ECG, and creatinine phosphokinase with myocardial banding (CPK with MB) data were collected 24 h before until 7 days after surgery. Atenolol (0, 5, or 10 mg) or placebo was administered intravenously before induction of anesthesia and every 12 h after operation until the patient could take oral medications. Atenolol (0, 50, or 100 mg) was administered orally once a day as specified by blood pressure and heart rate.

Results
During the postoperative period, the incidence of myocardial ischemia was significantly reduced in the atenolol group: days 0-2 (atenolol 17 of 99 patients; placebo, 34 of 101 patients; P = 0.008) and days 0-7 (atenolol, 24 of 99 patients; placebo, 39 of 101 patients; P = 0.029). Patients with episodes of myocardial ischemia were more likely to die in the next 2 yr (P = 0.025).

Conclusions
Perioperative administration of atenolol for 1 week to patients at high risk for coronary artery disease significantly reduces the incidence of postoperative myocardial ischemia. Reductions in perioperative myocardial ischemia are associated with reductions in the risk for death at 2 yr.
The Effects of Fentanyl on Sevoflurane Requirements for Loss of Consciousness and Skin Incision
Authors: Katoh Takasumi , Ikeda Kazuyuki 
Published: November 2003

Background
Fentanyl produces a minimal reduction in the minimum alveolar concentration of sevoflurane to prevent response to a verbal command in 50% of patients (MAC[awake]) at low but analgesic plasma concentrations. The reduction in MAC(awake), however, is still unknown at higher fentanyl concentrations. The reduction in the MAC of sevoflurane by fentanyl has not been described accurately. The purpose of this study was to determine the MAC(awake) and MAC reduction of sevoflurane by fentanyl.

Methods
Ninety-two patients were randomly allocated to seven fentanyl concentration groups (target plasma concentrations of 0, 1, 1.5, 3, 6, 10, and 14 ng/ml). Responses to verbal command were observed for MAC(awake) assessment at predetermined sevoflurane concentrations. Thereafter, in patients whose target fentanyl concentration was 0 to 10 ng/ml, responses to skin incision were observed for MAC assessment at new steady-state sevoflurane concentrations. The reduction in the MAC(awake) and MAC of sevoflurane by the measured fentanyl concentration was calculated.

Results
There was an initial steep reduction in the MAC of sevoflurane by fentanyl, with 3 ng/ml resulting in a 59% MAC reduction. A ceiling effect was observed, with 10 ng/ml providing only a further 17% reduction in MAC. The initial reduction in MAC(awake) was not as steep as that in MAC. Fentanyl reduced MAC(awake) by approximately 24% at a plasma concentration of 3 ng/ml. Although the reduction curve of MAC(awake) was parabolic, no manifest ceiling effect was observed at concentrations administered in the present study.

Conclusions
The reduction in sevoflurane requirements for loss of consciousness and skin incision by fentanyl was determined. Fentanyl reduced both requirements, but the mode of the reduction was not comparable.
Bispectral Analysis of the Electroencephalogram Predicts Conscious Processing of Information during Propofol Sedation and Hypnosis
Authors: Kearse Lee A. , Rosow Carl , Zaslavsky Alan , Connors Patricia , Dershwitz Mark , Denman William 
Published: November 2003

Background
The bispectral index (BIS) measures changes in the interfrequency coupling of the electroencephalogram (EEG). The purposes of this study were (1) to determine whether BIS correlates with responses to command during sedation and hypnosis induced by propofol or propofol and nitrous oxide, and (2) to compare BIS to targeted and measured concentrations of propofol in predicting participants' responses to commands.

Methods
Twenty volunteers (15 men and 5 women, aged 22-50 yr) were given propofol by computer-controlled infusion, and EEG was recorded for off-line analysis of BIS. Responses to randomly ordered verbal commands or voice plus touch were measured with two categorical scales (CS1 and CS2, respectively). All subjects received a propofol infusion targeted to achieve effect site concentrations of 1, 2, 4, 2, 1, and 0 microg/ml. Ten participants had repeated infusion, whereas 10 others breathed 30% nitrous oxide and oxygen and received a propofol infusion targeted for 0.5, 1, 2, 4, 2, 1, 0.5, and 0 microg/ml. Five minutes after each targeted concentration had been reached, CS1, CS2, and arterial propofol concentration were determined. The area under the receiver operating characteristic curve was used to compare the accuracy of (1) BIS, (2) targeted propofol concentration, (3) measured concentration, and (4) treatment history as predictors of response.

Results
Bispectral index was a strong predictor of CS1 and CS2 (P < 0.0001) and significantly more accurate than targeted or measured propofol concentrations (P < 0.0003 and P < 0.003, respectively). It also provided additional predictive power when combined with treatment history (P < 0.02). Nitrous oxide slightly decreased the probability of response at a given value of BIS (P < 0.05), but accuracy was unaffected.

Conclusions
Bispectral index accurately predicts response to verbal commands during sedation and hypnosis with propofol or propofol plus nitrous oxide. Accuracy is maintained in situations likely to be encountered during clinical use: when propofol concentrations are increasing or decreasing and when repeated measurements are made over time.
Fentanyl Augments the Blockade of the Sympathetic Response to Incision (MAC-BAR) Produced by Desflurane and Isoflurane
Authors: Daniel Malcolm , Weiskopf Richard B. , Noorani Mariam , Eger Edmond I. 
Published: November 2003

Background
Heart rate (HR) or mean arterial blood pressure (MAP) may increase in response to incision despite the absence of a motor response. The authors hypothesized that the MAC-BAR (minimum alveolar concentration of an anesthetic that blocks adrenergic response to incision) for isoflurane would exceed that for desflurane, and that fentanyl would decrease the MAC-BAR for each anesthetic in a dose-dependent manner.

Methods
Seventy-one patients were randomly allocated to one of six groups: desflurane or isoflurane without fentanyl or with 1.5 or 3 microg/kg fentanyl given intravenously 5 min before surgical incision. Anesthesia was induced with 2 mg/kg propofol given intravenously, and tracheal intubation facilitated with 0.1 mg/kg given intravenously. The first patient in each group received 1 MAC (end-tidal) of the inhaled anesthetic in 60% nitrous oxide (0.55 MAC), balance oxygen, maintained for at least 10 min before incision. The response was considered positive if the HR or MAP increased 15% or more. If the response was positive, the end-tidal concentration given to the next patient was 0.3 MAC greater; if the response was negative, the end-tidal concentration was 0.3 MAC less. The MAC-BAR level was calculated as the mean of four independent cross-over responses in each group.

Results
Desflurane and isoflurane anesthesia with 60% nitrous oxide did not change HR (P > 0.05) and decreased MAP (P < 0.05) before incision. Plasma epinephrine and norepinephrine concentrations after anesthesia and before incision were normal in all groups. The MAC-BAR level, without fentanyl, did not differ (P > 0.05) between desflurane (1.30 +/- 0.34 MAC [mean +/- SD]) and isoflurane (1.30 +/- 0.18 MAC). Fentanyl given at 1.5 microg/kg intravenously equivalently (P > 0.05) reduced the MAC-BAR for desflurane (to 0.40 +/- 0.18 MAC; P < 0.05) and isoflurane (to 0.55 +/- 0.00 MAC; P < 0.05), but a further increase in fentanyl to 3 microg/kg caused no greater decrease in the MAC-BAR for desflurane (0.48 +/- 0.16 MAC) and isoflurane (0.40 +/- 0.30 MAC).

Conclusions
Clinically attainable doses of desflurane and isoflurane, in 60% nitrous oxide (0.55 MAC), block the cardiovascular response to surgical incision at 1.3 MAC. Fentanyl given at 1.5 microg/kg decreases the MAC-BAR for each agent with no further decrease produced by 3 microg/kg fentanyl.
Accuracy of a Cerebral Oximeter in Healthy Volunteers under Conditions of Isocapnic Hypoxia
Authors: Henson Lindsey C. , Calalang Carolyn , Temp John A. , Ward Denham S. 
Published: November 2003

Background
A cerebral oximeter measures oxygen saturation of brain tissue noninvasively by near infrared spectroscopy. The accuracy of a commercially available oximeter was tested in healthy volunteers by precisely controlling end-tidal oxygen (P[ET]O2) and carbon dioxide (P[ET]CO2) tensions to alter global cerebral oxygen saturation.

Methods
In 30 healthy volunteers, dynamic end-tidal forcing was used to produce step changes in P[ET]O2 resulting in arterial saturation ranging from approximately 70% to 100% under conditions of controlled normocapnia (each person's resting P[ET]CO2) or hypercapnia (resting plus 7-10 mmHg). Blood arterial (SaO2) and jugular bulb venous (S[jv]O2) saturations during each P(ET)O2 interval were determined by co-oximetry. The cerebral oximeter reading (rSO2) and an estimated jugular venous saturation (S[jv]O2), derived from a combination of SaO2 and rSO2, were compared with the measured S(jv)O2.

Results
The S(jv)O2 was significantly higher with hypercapnia than with normocapnia for the same SaO2. The rSO2 and S(jv)O2 were both highly correlated with S(jv)O2 for individual volunteers (mean r2 = 0.91 for each relation); however, the slopes and intercepts varied widely among volunteers. In three of them, the cerebral oximeter substantially underestimated the measured S(jv)O2.

Conclusions
During isocapnic hypoxia in healthy persons, cerebral oxygenation as estimated by near infrared spectroscopy precisely tracks changes in measured S(jv)O2 within individuals, but the relation exhibits a wide range of slopes and intercepts. Therefore the clinical utility of the device is limited to situations in which tracking trends in cerebral oxygenation would be acceptable.
Low-dose Ondansetron with Dexamethasone More Effectively Decreases Vomiting after Strabismus Surgery in Children than Does High-dose Ondansetron
Authors: Splinter William M. , Rhine Elliot J. 
Published: November 2003

Background
Ondansetron and dexamethasone have been observed to decrease the incidence of vomiting by children after general anesthesia. This study compared the effect of high-dose (150 microg/kg) ondansetron with low-dose (50 microg/kg) ondansetron plus 150 microg/kg dexamethasone on the incidence of vomiting after strabismus in children.

Methods
This study had a double-blind, blocked, stratified, randomized design. With parental consent and Hospital Ethics Committee approval, healthy children aged 2-14 yr who were undergoing elective strabismus surgery were studied. Anesthesia was induced intravenously with propofol or by inhalation with halothane and nitrous oxide. Patients in the high-dose group were given placebo plus 150 microg/kg (maximum dose, 8 mg) of ondansetron intravenously, whereas patients in the low-dose group were given 150 microg/kg dexamethasone (maximum dose, 8 mg) and 50 microg/kg ondansetron intravenously in a double-blind manner. Anesthesia was maintained with halothane and nitrous oxide. All incidences of vomiting occurring as long as 24 h after anesthesia were recorded.

Results
Three of the 200 patients enrolled in the study were excluded from data analysis. The groups were similar with respect to demographic data and potential confounding variables. Patients vomited from 0-12 times. The low-dose ondansetron plus dexamethasone group had a lower incidence of vomiting, 9% (95% CI = 4-17%) versus 28% (95% CI = 20-38%; P < 0.001). Only 1% of the patients in the low-dose ondansetron plus dexamethasone group vomited while in the hospital.

Conclusions
Low-dose ondansetron plus dexamethasone is an effective prophylactic antiemetic combination for children undergoing strabismus surgery.
Headache after Attempted Epidural Block
Authors: Aida Sumihisa , Taga Kiichiro , Yamakura Tomohiro , Endoh Hiroshi , Shimoji Koki 
Published: November 2003

Background
Postmeningeal puncture headache (PMPH) is typically attributed to the loss of cerebrospinal fluid (CSF). However, when it occurs after an attempted epidural puncture, it may be due to either CSF loss or, potentially, to the subarachnoid injection of air used as a part of "loss-of-resistance" testing. This study was performed to examine the relation between intrathecal air and PMPH.

Methods
Using a loss-of-resistance test with an air-filled (n = 1,812; air group) or saline-filled (n = 1,918; saline group) syringe, epidural block was performed in patients with acute or chronic pain. The dura was judged to be perforated not only when backflow of CSF was recognized in the needle but also when signs and symptoms solely attributable to meningeal perforation were seen, such as high spinal blockade or severe motor blockade. The incidence, onset time, and duration of PMPH in the air and saline groups were compared. In all patients with signs of meningeal perforation, brain computed tomography was examined.

Results
The incidence of PMPH in the air group (32 cases) was significantly higher than that in the saline group (5 cases), although the occurrences of meningeal perforation between the air (48 cases) and saline (51 cases) groups did not differ significantly. Intrathecal air bubbles were detected on brain computed tomography in both the deep supraspinal structures such as the ventricles, Silvian fissures and cisterns, and the superficial subarachnoid space in 30 of 32 patients with PMPH in the air group, whereas no intrathecal air bubbles were seen in the saline group. PMPH was significantly more rapid in onset and shorter in duration in the air group than that in the saline group.

Conclusions
The use of air for loss-of-resistance testing during epidural block was associated with a higher incidence of PMPH, which might be attributable to subarachnoid air injection and CSF leakage.
Physostigmine Prevents Postanesthetic Shivering As Does Meperidine or Clonidine
Authors: Horn Ernst-Peter , Standl Thomas , Sessler Daniel I. , von Knobelsdorff Georg , Buchs Christine , Schulte am Esch Jochen 
Published: November 2003

Background
Postanesthetic shivering develops in as many as one half of patients recovering from isoflurane anesthesia. Cholinergic stimulation of the hypothalamic-pituitary-adrenal axis and adrenal medulla by physostigmine enhances secretion of arginine vasopressin, epinephrine, and norepinephrine. Because the hypothalamus is the dominant thermoregulatory controller in mammals, and these neurotransmitters may be involved in body temperature control, physostigmine administration may influence the incidence of shivering. Accordingly, the authors tested the hypothesis that physostigmine administration inhibits postanesthetic shivering. Its efficacy was compared with that of saline (negative control) and meperidine and clonidine (positive controls).

Methods
Sixty patients having surgery of the ear or nose were tested. General anesthesia was induced with 2 mg/kg propofol, 0.1 mg/kg vecuronium, and 1.5 microg/kg fentanyl and maintained with isoflurane (1.5 +/- 0.4%) in 70% nitrous oxide. At the end of surgery, the patients were randomly assigned to receive an intravenous bolus of 0.04 mg/kg physostigmine, isotonic saline, 0.5 mg/kg meperidine, or 1.5 microg/kg clonidine. Heart rate, mean arterial blood pressure, oxygen saturation, visual analog pain score, temperature, and postanesthetic shivering were measured during recovery.

Results
Postanesthetic shivering occurred in 6 of 15 (40%) patients given saline. In contrast, postanesthetic shivering was significantly reduced in physostigmine-treated patients (1 of 15, or 7%) and was absent in patients given clonidine or meperidine.

Conclusions
Physostigmine inhibited shivering as well as did two established treatments, meperidine and clonidine. These data suggest that cholinergic systems contribute to the genesis and control of postanesthetic shivering.
Modulation of the Cardiac Sodium Current by Inhalational Anesthetics in the Absence and Presence of β-Stimulation
Authors: Weigt Henry U. , Kwok Wai-Meng , Rehmert Georg C. , Bosnjak Zeljko J. 
Published: November 2003

Background
Cardiac dysrhythmias during inhalational anesthesia in association with catecholamines are well known, and halothane is more "sensitizing" than isoflurane. However, the underlying mechanisms of action of volatile anesthetics with or without catecholamines on cardiac Na channels are poorly understood. In this study, the authors investigated the effects of halothane and isoflurane in the absence and presence of beta-stimulation (isoproterenol) on the cardiac Na+ current (INa) in ventricular myocytes enzymatically isolated from adult guinea pig hearts.

Methods
A standard whole-cell patch-clamp technique was used. The INa was elicited by depolarizing test pulses from a holding potential of -80 mV in reduced Na+ solution (10 mM).

Results
Isoproterenol alone depressed peak INa significantly by 14.6 +/- 1.7% (means +/- SEM). Halothane (1.2 mM) and isoflurane (1.0 mM) also depressed peak INa significantly by 42.1 +/- 3.4% and 21.3 +/- 1.9%, respectively. In the presence of halothane, the effect of isoproterenol (1 microM) was potentiated, further decreasing peak INa by 34.7 +/- 4.1%. The halothane effect was less, although significant, in the presence of a G-protein inhibitor (GDPbetaS) or a specific protein kinase A inhibitor [PKI-(6-22)-amide], reducing peak INa by 24.2 +/- 3.3% and 24 +/- 2.4%, respectively. In combination with isoflurane, the effect of isoproterenol on INa inhibition was less pronounced, but significant, decreasing current by 12.6 +/- 3.9%. GDPbetaS also reduced the inhibitory effect of isoflurane. In contrast, PKI-(6-22)-amide had no effect on isoflurane INa inhibition.

Conclusions
These results suggest two distinct pathways for volatile anesthetic modulation on the cardiac Na+ current: (1) involvement of G proteins and a cyclic adenosine monophosphate (cAMP)-mediated pathway for halothane and, (2) a G-protein-dependent but cAMP-independent pathway for isoflurane. Furthermore, these studies show that the inhibition of cardiac INa by isoproterenol is enhanced in the presence of halothane, suggesting some form of synergistic interaction between halothane and isoproterenol.