bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of Bronchoprotection by Anesthetic Induction Agents
Authors: Brown Robert H. , Wagner Elizabeth M. 
Published: November 2003

Background
Propofol and ketamine have been purported to decrease bronchoconstriction during induction of anesthesia and intubation. Whether they act on airway smooth muscle or through neural reflexes has not been determined. We compared propofol and ketamine to attenuate the direct activation of airway smooth muscle by methacholine and limit neurally mediated bronchoconstriction (vagal nerve stimulation).

Methods
After approval from the institutional review board, eight sheep were anesthetized with pentobarbital, paralyzed, and ventilated. After left thoracotomy, the bronchial artery was cannulated and perfused. In random order, 5 mg/ml concentrations of propofol, ketamine, and thiopental were infused into the bronchial artery at rates of 0.06, 0.20, and 0.60 ml/min. After 10 min, airway resistance was measured before and after vagal nerve stimulation and methacholine given via the bronchial artery. Data were expressed as a percent of baseline response before infusion of drug and analyzed by analysis of variance with significance set at P< or =0.05.

Results
Systemic blood pressure was not affected by any of the drugs (P>0.46). Baseline airway resistance was not different among the three agents (P = 0.56) or by dose (P = 0.96). Infusion of propofol and ketamine into the bronchial artery caused a dose-dependent attenuation of the vagal nerve stimulation-induced bronchoconstriction to 26+/-11% and 8+/-2% of maximum, respectively (P<0.0001). In addition, propofol caused a significant decrease in the methacholine-induced bronchoconstriction to 43+/-27% of maximum at the highest concentration (P = 0.05)

Conclusions
The local bronchoprotective effects of ketamine and propofol on airways is through neurally mediated mechanisms. Although the direct effects on airway smooth muscle occur at high concentrations, these are unlikely to be of primary clinical relevance.
Continuous Arterial PO(2) and PCO(2) Measurements in Swine during Nitrous Oxide and Xenon Elimination
Authors: Calzia Enrico , Stahl Wolfgang , Handschuh Thomas , Marx Thomas , Froba Gebhardt , Georgieff Michael , Radermacher Peter 
Published: November 2003

Background
During nitrous oxide (N2O) elimination, arterial oxygen tension (PaO2) decreases because of the phenomenon commonly called diffusive hypoxia. The authors questioned whether similar effects occur during xenon elimination.

Methods
Nineteen anesthetized and paralyzed pigs were mechanically ventilated randomly for 30 min using inspiratory gas mixtures of 30% oxygen and either 70% N2O or xenon. The inspiratory gas was replaced by a mixture of 70% nitrogen and 30% oxygen. PaO2 and carbon dioxide tensions were recorded continuously using an indwelling arterial sensor.

Results
The PaO2 decreased from 119+/-10 mm Hg to 102+/-12 mm Hg (mean+/-SD) during N2O washout (P<0.01) and from 116+/-9 mm Hg to 110+/-8 mm Hg during xenon elimination (P<0.01), with a significant difference (P<0.01) between baseline and minimum PaO2 values (deltaPaO2, 17+/-6 mm Hg during N2O washout and 6+/-3 mm Hg during xenon washout). The PaCO2 value also decreased (from 39.3+/-6.3 mm Hg to 37.6+/-5.8 mm Hg) during N2O washout (P<0.01) and during xenon elimination (from 35.4+/-1.6 mm Hg to 34.9+/-1.6 mm Hg; P< 0.01). The deltaPaCO2 was 1.7+/-0.9 mm Hg in the N2O group and 0.5+/-0.3 mm Hg in the xenon group (P<0.01).

Conclusion
Diffusive hypoxia is unlikely to occur during recovery from xenon anesthesia, probably because of the low blood solubility of this gas.
Relative Analgesic Potencies of Ropivacaine and Bupivacaine for Epidural Analgesia in Labor
Authors: Polley Linda S. , Columb Malachy O. , Naughton Norah N. , Wagner Deborah S. , van de Ven Cosmas J. M. 
Published: November 2003

Background
The minimum local analgesic concentration (MLAC) has been defined as the median effective local analgesic concentration in a 20-ml volume for epidural analgesia in the first stage of labor. The aim of this study was to assess the relative analgesic potencies of epidural bupivacaine and ropivacaine by determining their respective minimum local analgesic concentrations.

Methods
Seventy-three parturients at < or = 7 cm cervical dilation who requested epidural analgesia were allocated to one of two groups in this double-blinded, randomized, prospective study. After a lumbar epidural catheter was placed, 20 ml of the test solution was given, either ropivacaine (n = 34) or bupivacaine (n = 39). The concentration of local anesthetic was determined by the response of the previous patient in that group to a higher or lower concentration using up-down sequential allocation. Analgesic efficacy was assessed using 100-mm visual analog pain scores with < or = 10 mm within 30 min defined as effective. An effective result directed a 0.01% wt/vol decrement for the next patient. An ineffective result directed a 0.01% wt/vol increment.

Results
The minimum local analgesic concentration of ropivacaine was 0.111% wt/vol (95% confidence interval, 0.100-0.122), and the minimum local analgesic concentration of bupivacaine was 0.067% wt/vol (95% confidence interval, 0.052-0.082). Ropivacaine was significantly less potent than bupivacaine, with a potency ratio of 0.6 (95% confidence interval, 0.49-0.74). No difference in motor effects was observed.

Conclusion
Ropivacaine was significantly less potent than bupivacaine for epidural analgesia in the first stage of labor.
Comparison of Adenosine and Remifentanil Infusions as Adjuvants to Desflurane Anesthesia
Authors: Zarate Eduardo , Sa Rego Monica M. , White Paul F. , Duffy Larry , Shearer Vance E. , Griffin James D. , Whitten Charles W. 
Published: November 2003

Background
Because adenosine has been alleged to produce both anesthetic and analgesic sparing effects, a randomized, double-blinded study was designed to compare the perioperative effects of adenosine and remifentanil when administered as intravenous adjuvants during general anesthesia for major gynecologic procedures.

Methods
Thirty-two women were assigned randomly to one of two drug treatment groups. After premedication with 0.04 mg/kg intravenous midazolam, anesthesia was induced with 2 micro/kg intravenous fentanyl, 1.5 mg/kg intravenous propofol, and 0.6 mg/kg intravenous rocuronium, and maintained with desflurane, 2%, and nitrous oxide, 65%, in oxygen. Before skin incision, an infusion of either remifentanil (0.02 microg x kg(-1) x min(-1)) or adenosine (25 microg x kg(-1) x min(-1)) was started and subsequently titrated to maintain systolic blood pressure, heart rate, or both within 10-15% of the preincision values.

Results
Adenosine and remifentanil infusions were effective anesthetic adjuvants during lower abdominal surgery. Use of adenosine (mean +/- SEM, 166+/-17 microg x kg(-1) x min(-1)) was associated with a significantly greater decrease in systolic blood pressure and higher heart rate values compared with remifentanil (mean +/- SEM, 0.2+/-0.03 microg kg(-1) x min(-1)). Total postoperative opioid analgesic use was 45% and 27% lower in the adenosine group at 0-2 h and 2-24 h after surgery, respectively.

Conclusions
Adjunctive use of a variable-rate infusion of adenosine during desflurane-nitrous oxide anesthesia was associated with acceptable hemodynamic stability during the intraoperative period. Compared with remifentanil, intraoperative use of adenosine was associated with a decreased requirement for opioid analgesics during the first 24 h after operation.
Factors Affecting the Pharmacokinetic Characteristics of Rapacuronium
Authors: Fisher Dennis M. , Kahwaji Raymond , Bevan David , Bikhazi George , Fragen Robert J. , Angst Martin S. , Ornstein Eugene , Matteo Richard S. 
Published: November 2003

Background
Rapacuronium is a new nondepolarizing muscle relaxant with rapid onset and offset. As part of a study to determine its neuromuscular effects, the authors sampled plasma sparsely to determine the influence of age, gender, and other covariates on its pharmacokinetic characteristics.

Methods
Of 181 patients receiving a single bolus dose of 0.5-2.5 mg/kg rapacuronium, 43 (aged 24-83 yr) had plasma sampled 3 or 4 times to determine plasma concentrations of rapacuronium and its metabolite, ORG9488. Pharmacokinetic analysis was performed using a population approach (mixed-effects modeling) to determine the influence of demographic characteristics and preoperative laboratory values on the pharmacokinetic parameters.

Results
Rapacuronium's weight-normalized plasma clearance was 7.03 x (1 - 0.0507 x (HgB - 13)) ml x kg(-1) x min(-1), where HgB is the patient's preoperative value for hemoglobin (g/100 ml); however, rapacuronium's blood clearance (11.4+/-1.4 ml x kg(-1) x min(-1), mean +/- SD) did not vary with hemoglobin. Rapacuronium's weight-normalized pharmacokinetic parameters were not influenced by age, gender, or other covariates examined. Plasma concentrations of ORG9488 were typically less than 14% those of rapacuronium during the initial 30 min after rapacuronium administration.

Conclusions
In this patient population, neither age nor gender influence elimination of rapacuronium. This finding contrasts to an age-related decrease in plasma clearance observed in a study of 10 healthy volunteers and in a pooled analysis of the pharmacokinetic data from 206 adults in multiple clinical studies. Even if ORG9488 has a potency similar to that of rapacuronium, its plasma concentrations after a single bolus dose of rapacuronium are sufficiently small to contribute minimally to neuromuscular blockade.
The Pharmacokinetics of Milrinone in Pediatric Patients after Cardiac Surgery
Authors: Bailey James M. , Miller Bruce E. , Lu Wei , Tosone Steven R. , Kanter Kirk R. , Tam Vincent K. H. 
Published: November 2003

Background
Milrinone has been shown to increase cardiac output in children after cardiac surgery, but pharmacokinetic analysis has not been used to identify effective dose regimens. The purpose of this study was to characterize the pharmacokinetics of milrinone in infants and children and to apply the results to the issue of dosing.

Methods
Twenty children were studied after they underwent repair of congenital cardiac defects. Control hemodynamic measurement was made after the children were separated from cardiopulmonary bypass, and each patient was given a loading dose of 50 microg/kg progressively in 5 min. Hemodynamic measurements were recorded again at the end of the loading dose and when a blood sample was taken to determine milrinone plasma concentrations. Further blood samples were taken during the next 16 h for milrinone plasma concentration analysis. The pharmacokinetics of milrinone were analyzed using the population pharmacokinetic program NONMEM.

Results
The loading dose of milrinone resulted in a mean decrease in mean blood pressure of 12% and a mean increase in cardiac index of 18% at a mean peak plasma concentration of 235 ng/ml. The pharmacokinetics of milrinone were best described by a three-compartment model. In the optimal model, all volumes and distribution clearances were proportional to weight, and weight-normalized elimination clearance was proportional to age; ie., Cl1 = 2.5 x weight x (1 + 0.058 x age) where Cl1 is expressed as ml/min, and the units of weight and age are kg and months, respectively.

Conclusions
A loading dose of 50 microg/kg effectively increases cardiac index in children after cardiac surgery. Simulations indicate that the peak plasma concentration can be maintained by following the loading dose of 50 microg/kg with an infusion of approximately 3 microg x kg(-1) x min(-1) for 30 min and then a maintenance infusion, which may require adjustment for age.
Lumbar Sympathetic Blocks Speed Early and Second Stage Induced Labor in Nulliparous Women
Authors: Leighton Barbara L. , Halpern Stephen H. , Wilson Donna B. 
Published: November 2003

Background
Rapid cervical dilation reportedly accompanies lumbar sympathetic blockade, whereas epidural analgesia is associated with slow labor. The authors compared the effects of initial lumbar sympathetic block with those of epidural analgesia on labor speed and delivery mode in this pilot study.

Methods
At a hospital not practicing active labor management, full-term nulliparous patients whose labors were induced randomly received initial lumbar sympathetic block or epidural analgesia. The latter patients received 10 ml bupivacaine, 0.125%; 50 microg fentanyl; and 100 microg epinephrine epidurally and sham lumbar sympathetic blocks. Patients to have lumbar sympathetic blocks received 10 ml bupivacaine, 0.5%; 25 microg fentanyl; and 50 microg epinephrine bilaterally and epidural catheters. Subsequently, all patients received epidural analgesia.

Results
Cervical dilation occurred more quickly (57 vs. 120 min/cm cervical dilation; P = 0.05) during the first 2 h of analgesia in patients having lumbar sympathetic blocks (n = 17) than in patients having epidurals (n = 19). The second stage of labor was briefer in patients having lumbar sympathetic blocks than in those having epidurals (105 vs. 270 min; P < 0.05). Nine patients having lumbar sympathetic block and seven having epidurals delivered spontaneously, whereas seven patients having lumbar sympathetic block and seven having epidurals had instrument-assisted vaginal deliveries. Cesarean delivery for fetal bradycardia occurred in one patient having lumbar sympathetic block. Cesarean delivery for dystocia occurred in five patients having epidurals compared with no patient having lumbar sympathetic block (P = not significant). Visual analog pain scores differed only at 60 min after block.

Conclusions
Nulliparous parturients having induced labor and receiving initial lumbar sympathetic blocks had faster cervical dilation during the first 2 h of analgesia, shorter second-stage labors, and a trend toward a lower dystocia cesarean delivery rate than did patients having epidural analgesia. The effects of lumbar sympathetic block on labor need to be determined in other patient groups. These results may help define the tocodynamic effects of regional labor analgesia.
Cardiopulmonary Resuscitation
Authors: Hevesi Zoltan G. , Thrush David N. , Downs John B. , Smith Robert A. 
Published: November 2003

Background
Conventional cardiopulmonary resuscitation (CPR) includes 80-100/min precordial compressions with intermittent positive pressure ventilation (IPPV) after every fifth compression. To prevent gastric insufflation, chest compressions are held during IPPV if the patient is not intubated. Elimination of IPPV would simplify CPR and might offer physiologic advantages, but compression-induced ventilation without IPPV has been shown to result in hypercapnia. The authors hypothesized that application of continuous positive airway pressure (CPAP) might increase CO2 elimination during chest compressions.

Methods
After appropriate instrumentation and measurement of baseline data, ventricular fibrillation was induced in 18 pigs. Conventional CPR was performed as a control (CPR(C)) for 5 min. Pauses were then discontinued, and animals were assigned randomly to receive alternate trials of uninterrupted chest compressions at a rate of 80/min without IPPV, either at atmospheric airway pressure (CPR(ATM)) or with CPAP (CPR(CPAP)). CPAP was adjusted to produce a minute ventilation of 75% of the animal's baseline ventilation. Data were summarized as mean +/- SD and compared with Student t test for paired observations.

Results
During CPR without IPPV, CPAP decreased PaCO2 (55+/-28 vs. 100+/-16 mmHg) and increased SaO2 (0.86+/-0.19 vs. 0.50+/-0.18%; P < 0.001). CPAP also increased arteriovenous oxygen content difference (10.7+/-3.1 vs. 5.5+/-2.3 ml/dl blood) and CO2 elimination (120+/-20 vs. 12+/-20 ml/min; P < 0.01). Differences between CPR(CPAP) and CPR(ATM) in aortic blood pressure, cardiac output, and stroke volume were not significant.

Conclusions
Mechanical ventilation may not be necessary during CPR as long as CPAP is applied. Discontinuation of IPPV will simplify CPR and may offer physiologic advantage.
Local Anesthetic Inhibition of Baseline Potassium Channels with Two Pore Domains in Tandem
Authors: Kindler Christoph H. , Yost Spencer C. , Gray Andrew T. 
Published: November 2003

Background
Recently, a new structural family of potassium channels characterized by two pore domains in tandem within their primary amino acid sequence was identified. These tandem pore domain potassium channels are not gated by voltage and appear to be involved in the control of baseline membrane conductances. The goal of this study was to identify mechanisms of local anesthetic action on these channels.

Methods
Oocytes of Xenopus laevis were injected with cRNA from five cloned tandem pore domain baseline potassium channels (TASK, TREK-1, TOK1, ORK1, and TWIK-1), and the effects of several local anesthetics on the heterologously expressed channels were assayed using two-electrode voltage-clamp and current-clamp techniques.

Results
Bupivacaine (1 mM) inhibited all studied tandem pore potassium channels, with TASK inhibited most potently. The potency of inhibition was directly correlated with the octanol: buffer distribution coefficient of the local anesthetic, with the exception of tetracaine, to which TASK is relatively insensitive. The approximate 50% inhibitory concentrations of TASK were 709 microM mepivacaine, 222 microM lidocaine, 51 microM R(+)-ropivacaine, 53 microM S(-)-ropivacaine, 668 microM tetracaine, 41 microM bupivacaine, and 39 microM etidocaine. Local anesthetics (1 mM) significantly depolarized the resting membrane potential of TASK cRNA-injected oocytes compared with saline-injected control oocytes (tetracaine 22+/-6 mV rs. 7+/-1 mV, respectively, and bupivacaine 31+/-7 mV vs. 6+/-4 mV).

Conclusions
Local anesthetics inhibit tandem pore domain baseline potassium channels, and they could depolarize the resting membrane potential of cells expressing these channels. Whether inhibition of these channels contributes to conduction blockade or to the adverse effects of local anesthetics remains to be determined.
Speed of Onset and Offset and Mechanisms of Ventilatory Depression from Sevoflurane
Authors: Dahan Albert , Olofsen Erik , Teppema Luc , Sarton Elise , Olievier Cees 
Published: November 2003

Background
Inhalational anesthetics depress breathing dose dependently. The authors studied the dynamics of ventilation on changes in end-tidal sevoflurane partial pressure. To learn more about the mechanisms of sevoflurane-induced respiratory depression, the authors also studied its influence on the dynamic ventilatory response to carbon dioxide.

Methods
Experiments were performed in cats anesthetized with alpha chloralose-urethane. For protocol 1, step changes in end-tidal sevoflurane partial pressure were applied and inspired ventilation was measured. Breath-to-breath inspired ventilation was related to the sevoflurane concentration in a hypothetical effect compartment based on an inhibitory sigmoid Emax model. For protocol 2, step changes in the end-tidal partial pressure of carbon dioxide were applied at 0, 0.5, and 1% end-tidal sevoflurane. The inspired ventilation-end-tidal partial pressure of carbon dioxide data were analyzed using a two-compartment model of the respiratory controller, which consisted of a fast peripheral and slow central compartment. Values are the mean +/- SD.

Results
In protocol 1, the effect-site half-life of respiratory changes caused by alterations in end-tidal sevoflurane partial pressure was 3.6+/-1.0 min. In protocol 2, at 0.50% sevoflurane, the central and peripheral carbon dioxide sensitivities decreased to 43+/-20% and 36+/-18% of control. At 1% sevoflurane, the peripheral carbon dioxide sensitivity decreased further, to 12+/-13% of control, whereas the central carbon dioxide sensitivity showed no further decrease.

Conclusions
Steady state inspired ventilation is reached after 18 min (i.e., 5 half-lives) on stepwise changes in end-tidal sevoflurane. Anesthetic concentrations of sevoflurane have, in addition to an effect on pathways common to the peripheral and central chemoreflex loops, a selective effect on the peripheral chemoreflex loop. Sevoflurane has similar effects on ventilatory control in humans and cats.
Effect of Systemic Morphine on the Responses of Convergent Neurons to Noxious Heat Stimuli Applied over Graded Surface Areas
Authors: Gall Olivier , Bouhassira Didier , Chitour Djamel , Le Bars Daniel 
Published: November 2003

Background
Stimulus intensity is a major determinant of the antinociceptive activity of opiates. This study focused on the influence of the spatial characteristics of nociceptive stimuli, on opiate-induced depressions of nociceptive transmission at the level of the spinal cord.

Methods
Anesthetized rats were prepared to allow extracellular recordings to be made from convergent neurons in the lumbar dorsal horn. The effects of systemic morphine (1 and 10 mg/kg) were compared with those of saline for thermal stimuli of constant intensity, applied to the area of skin surrounding the excitatory receptive field (1.9 cm2) or to a much larger adjacent area (18 cm2).

Results
The responses (mean +/- SD) elicited by the 1.9-cm2 stimulus were not modified by 1 mg/kg intravenous morphine, although they were decreased by the 10-mg/kg dose (to 11+/-4% of control values compared with saline; P < 0.05). In contrast, when the 18-cm2 stimulus was applied, 1 mg/kg intravenous morphine produced a paradoxical facilitation of the neuronal responses (159+/-36% of control values; P < 0.05) and 10 mg/kg intravenous morphine resulted in a weaker depression of the responses (to 42+/-24% of control values; P < 0.05) than was observed with the smaller stimulus.

Conclusions
Doses of systemic morphine in the analgesic range for rats had dual effects on nociceptive transmission at the level of the spinal cord, depending on the surface area that was stimulated. Such effects are difficult to explain in terms of accepted pharmacodynamic concepts and may reflect an opioid-induced depression of descending inhibitory influences triggered by spatial summation.