bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Temperature on Cerebral Tissue Oxygen Tension, Carbon Dioxide Tension, and pH during Transient Global Ischemia in Rabbits
Authors: Bacher Andreas , Kwon Jae Young , Zornow Mark H.
Published: November 2003

Background

A decrease in brain temperature (Tbrain) causes a decrease in the cerebral metabolic rate for oxygen (CMRO2) and provides potent neuroprotection against ischemic damage. In the present study, the effects of mild to moderate hypothermia on cerebral tissue oxygen tension (PO2 brain), carbon dioxide tension (PCO2 brain), and pH (pHbrain) were monitored during short episodes of global cerebral ischemia.

Methods

After approval by the Animal Care and Use Committee, 10 New Zealand white rabbits were anesthetized (1% halothane in air) and mechanical ventilation was adjusted to maintain the arterial carbon dioxide tension at 35 mmHg (alpha-stat). A sensor to measure PO2 brain, PCO2 brain, pHbrain, and Tbrain was inserted into the brain through a burr hole in the skull. Tbrain was adjusted to 38 degrees C, 34.4 degrees C, and 29.4 degrees C in a random sequence in each animal. PO2 brain, PCO2brain, and pHbrain (all variables are reported at the actual Tbrain) were recorded every 10 s during a 5-min baseline, 3 min of cerebral ischemia induced by inflation of a neck tourniquet, and 10 min of reperfusion at each level of Tbrain. Analysis of variance and Dunnett's test were used for statistical analysis. Data are presented as means +/- SD.

Results

During ischemia, PO2 brain decreased from 56 +/- 3 to 33 +/- 2 mmHg at 38 degrees C, from 58 +/- 3 to 32 +/- 3 mmHg at 34.4 degrees C, and from 51 +/- 2 to 32 +/- 2 mmHg at 29.4 degrees C (p = NS). PCO2 brain increased by 6.7 +/- 2 mmHg at 38 degrees C, by 5.1 +/- 1.4 mmHg at 34.4 degrees C, and by 2.3 +/- 0.8 mmHg at 29.4 degrees C. pHbrain inversely followed the trend of PCO2 brain.

Conclusions

The attenuated increase in PCO2 brain during hypothermic ischemia results from the reduced CMRO2. The similar decrease in PO2 brain at all temperature levels indicates that despite the reduction in CMRO2, PO2 brain is no better preserved during brief episodes of hypothermic ischemia than during normothermic ischemia.
Selective Pulmonary Vasodilation Induced by Aerosolized Zaprinast
Authors: Ichinose Fumito , Adrie Christophe , Hurford William E. , Bloch Kenneth D. , Zapol Warren M.
Published: November 2003

Background

Zaprinast, an inhibitor of guanosine-3',5'-cyclic monophosphate (cGMP)-selective phosphodiesterase, augments smooth muscle relaxation induced by endothelium-dependent vasodilators (including inhaled nitric oxide [NO]). The present study was designed to examine the effects of inhaled nebulized zaprinast, alone, and combined with inhaled NO.

Methods

Eight awake lambs with U46619-induced pulmonary hypertension sequentially breathed two concentrations of NO (5 and 20 ppm), followed by inhalation of aerosols generated from solutions containing four concentrations of zaprinast (10, 20, 30, and 50 mg/ml). The delivered doses of nebulized zaprinast at each concentration (mean +/- SD) were 0.23 +/- 0.06, 0.49 +/- 0.14, 0.71 +/- 0.24, and 1.20 +/- 0.98 mg x kg(-1) x min(-1), respectively. Each lamb also breathed NO (5 and 20 ppm) and zaprinast (0.23 +/- 0.06 mg x kg[-1] x min[-1]) in combination after a 2-h recovery period.

Results

Inhaled NO selectively dilated the pulmonary vasculature. Inhaled zaprinast selectively dilated the pulmonary circulation and potentiated and prolonged the pulmonary vasodilating effects of inhaled NO. The net transpulmonary release of cGMP was increased by inhalation of NO, zaprinast, or both. The duration of the vasodilation induced by zaprinast inhalation was greater than that induced by NO inhalation.

Conclusions

Aerosolization of a cGMP-selective phosphodiesterase inhibitor alone or combined with NO may be a useful noninvasive therapeutic method to treat acute or chronic pulmonary hypertension.
Myocardial Infarction after Noncardiac Surgery
Authors: Badner Neal H. , Knill Richard L. , Brown James E. , Novick Teresa V. , Gelb Adrian W.
Published: November 2003

Background

In this study, the authors intensively monitored isoenzyme and electric activity of the heart for the first 7 days after noncardiac surgery in a large group of patients at risk for postoperative myocardial infarction (PMI).

Methods

After institutional review board approval and written informed consent were received, 323 patients, aged 50 yr or older, who had ischemic heart disease and presented for noncardiac surgery, were enrolled in this prospective, blinded study. After operation, patients had daily clinical assessments, electrocardiograms, and measurements of creatine kinase (CK), CK-2 (mass and activity), and Troponin-T on the operative night, twice daily on postoperative days 1-4, and then daily on days 5-7. A diagnosis of PMI was made if the total CK was > 174 U/l and in the presence of two of the following: (1) CK-2/CK (mass or activity) > 5%, (2) new Q waves lasting > or = 0.04 s and 1 mm deep in at least two contiguous leads, (3) Troponin-T was > 0.2 microg/l, or (4) a positive result of pyrophosphate scan.

Results

Eighteen of the 323 patients (5.6%) had a PMI, of which 3 (17%) were fatal. Only 3 of 18 patients had chest pain, whereas 10 of 18 patients (56%) had other clinical findings. The electrocardiographic classification of the PMI was Q wave in 6, non-Q wave in 10, and indeterminate in 2. The PMIs occurred on the day of operation in 8, on day one in 6, on day two in 3, and on day four in 1 patient.

Conclusions

This study determined that PMI was an early event, only occasionally associated with chest pain, and usually non-Q wave in nature.
Intrathecal Clonidine Combined with Sufentanil for Labor Analgesia
Authors: Gautier Philippe E. , De Kock Marc , Luc Fanard , Van Steenberge Albert , Hody Jean-Luc
Published: November 2003

Background

Intrathecal sufentanil provides rapid-onset and complete analgesia for the first stage of labor. The dose required to produce this effect can be associated with maternal respiratory depression, hypotension, nausea, or pruritus. Because clonidine potentiates the analgesic effects of opioids without increasing their side effects, the authors wanted to determine the efficacy of low doses of intrathecal clonidine (15 and 30 microg) combined with sufentanil.

Methods

Ninety-eight parturient requesting labor analgesia were studied. In a combined spinal-epidural technique, patients were randomly assigned to receive one of the following intrathecal solutions: either 15 microg clonidine (n = 10); 30 microg clonidine (n = 10); 2.5 microg sufentanil (n = 13); 5 microg sufentanil (n = 13); 2.5 microg sufentanil and 15 microg clonidine (n = 13); 2.5 microg sufentanil and 30 microg clonidine (n = 13); 5 microg sufentanil and 15 microg clonidine (n = 13); or 5 microg sufentanil and 30 microg clonidine (n = 13). Visual analog scores for pain, blood pressure, heart rate, sensory levels, incidence of nausea and pruritus, and motor blockade, and maternal and cord blood concentrations of clonidine were recorded.

Results

Patients receiving 30 microg intrathecal clonidine with 2.5 or 5 microg intrathecal sufentanil had significantly longer-lasting analgesia (145 +/- 36 and 145 +/- 43 min vs. 104 +/- 35 for those receiving 5 microg intrathecal sufentanil alone). Clonidine levels were undetectable in maternal serum.

Conclusions

Thirty micrograms of intrathecal clonidine combined with 2.5 or 5 microg intrathecal sufentanil significantly increased the duration of analgesia during the first stage of labor without adverse maternal or fetal effects.
Application of Physiologic Models to Predict the Influence of Changes in Body Composition and Blood Flows on the Pharmacokinetics of Fentanyl and Alfentanil in Patients
Authors: Bjorkman Sven , Wada Russell D. , Stanski Donald
Published: November 2003

Background

The influence of changes in the physiologic state of a patient on the disposition of fentanyl and alfentanil is poorly understood. The aims of this study were to determine whether physiologic pharmacokinetic models for fentanyl and alfentanil, based on data from rats, could predict plasma concentrations of these opioids in humans and to determine how changes in physiology would influence the predictions of their disposition.

Methods

The predictions of the models were tested against plasma concentration data from published pharmacokinetic studies. The influences of changes in body composition, cardiac output, and regional blood flows on the disposition of the opioids were simulated.

Results

The models could predict independently measured plasma concentrations of the opioids after short infusions in humans. Simulations then predicted that differences in body composition between men and women would have little influence on the pharmacokinetics of the opioids. Changes in cardiac output would affect drug redistribution, and consequently the early decay of the plasma concentrations, but not markedly influence rates of elimination. Further, the clearance of the opioids would decrease and their volumes of distribution increase with the age of the patient, but this would only marginally affect the early disposition of the drugs. Even large fluctuations in peripheral or hepatic blood flows would have modest effects on arterial plasma concentrations of the opioids, and sudden "postoperative" increases in peripheral blood flows would cause minor secondary plasma concentration peaks.

Conclusions

The ability of the physiologic models to predict plasma concentrations of fentanyl and alfentanil in humans was confirmed. When changes in physiologic condition were simulated, effects on the pharmacokinetics of the opioids with possible implications for dosing were obtained only if cardiac output was varied over a wide range.
Perioperative Risk of Bradyarrhythmias in Patients with Asymptomatic Chronic Bifascicular Block or Left Bundle Branch Block
Authors: Gauss Albrecht , Hubner Christine , Radermacher Peter , Georgieff Michael , Schutz Wolfram
Published: November 2003

Background

The incidence of perioperative bradyarrhythmias in patients with bifascicular or left bundle branch block (LBBB) and the influence of an additional first-degree atrioventricular (A-V) block has not been evaluated with 24-h Holter electrocardiographic monitoring. Therefore the authors assessed the rate of block progression and bradyarrhythmia in these patients.

Methods

Patients (n = 106) with asymptomatic bifascicular block or LBBB with or without an additional first-degree A-V block scheduled for surgery under general or regional anesthesia were enrolled prospectively. Three patients were excluded. Of the 103 remaining, 56 had a normal P-R interval and 47 had a prolonged one. Holter monitoring (CM2, CM5) was applied to each patient just before induction of anesthesia and was performed for 24 h. The primary endpoint of the study was the occurrence of block progression. As secondary endpoints, bradycardias < 40 beats/min with hemodynamic compromise (systolic blood pressure < 90 mmHg) or asystoles > 5 s were defined.

Results

Block progression to second-degree A-V block and consecutive cardiac arrest occurred in one case of LBBB without a prolonged P-R interval Severe bradyarrhythmias with hypotension developed in another eight patients: asystoles > 5 s occurred in two cases and six patients had bradycardias < 40/min. Pharmacotherapy was successful in these eight patients. There was no significant difference for severe bradyarrhythmias associated with hemodynamic compromise between patients with and without P-R prolongation (P = 1.00).

Conclusions

In patients with chronic bifascicular block or LBBB, perioperative progression to complete heart block is rare. However, the rate of bradyarrhythmias with hemodynamic compromise proved to be relevant. Because an additional first-degree A-V block did not increase the incidence of severe bradyarrhythmias and pharmacotherapy by itself was successful in nearly all cases, routine prophylactic insertion of a temporary pacemaker in such patients should be questioned.
Patient-controlled Epidural Analgesia with Bupivacaine and Fentanyl on Hospital Wards
Authors: Liu Spencer S. , Allen Hugh W. , Olsson Gayle L.
Published: November 2003

Background

The efficacy and safety of patient-controlled epidural analgesia (PCEA) for postoperative analgesia on hospital wards was studied.

Methods

Postoperative analgesia was provided for 1,030 patients with PCEA using 0.05% bupivacaine and fentanyl, 4 microg/ml, in a standardized manner. Patients were seen at least twice a day by the staff of the anesthesia pain management service. Prospectively gathered data included verbal pain scores at rest and activity (0-10); consumption of bupivacaine and fentanyl; and incidences of pruritus, nausea, sedation, hypotension, motor block, and respiratory depression. Descriptive statistics were used. Risk factors for side effects were determined using logistic regression.

Results

The study included 552 women and 477 men who underwent a median (mode) of 3 (2) days of PCEA. Their mean age was 59 +/- 16 yr and their mean weight was 76 +/- 19 kg. There were 454 abdominal, 165 gynecologic, 126 urologic, 108 vascular, 90 thoracic, 83 orthopedic, and 4 plastic surgical procedures. Median (mode) pain scores were 1 (0) at rest and 4 (5) with activity on postoperative day 1. Incidences of side effects were 16.7% (pruritus), 14.8% (nausea), 13.2% (sedation), 6.8% (hypotension), 2% (motor block), and 0.3% (respiratory depression). Reasons for termination of PCEA were elective (82%), displaced epidural catheter (12%), anticoagulation (3%), infection (1%), side effects (1%), inadequate analgesia (1%), and other (<1%). Risk factors for side effects were female sex, patient weight <73 kg, patient age <58 yr, bupivacaine and fentanyl consumption >9 ml/h, use of analgesic adjuncts, and lumbar placement of epidural catheters.

Conclusion

Patient-controlled epidural analgesia provides effective and safe postoperative analgesia on hospital wards.
Pharmacokinetic Analysis of the Effect of Vecuronium in Surgical Patients
Authors: Warwick Neil R. , Graham Garry G. , Torda Thomas A.
Published: November 2003

Background

Methods of the kinetic analysis of vecuronium based on effect only were developed but have been limited by the short time period of the studies. Using a multicompartment model and sequential dosing, the authors studied the ability of tests to determine most pharmacokinetic and pharmacodynamic parameters of vecuronium without measuring plasma concentrations.

Methods

The time course of neuromuscular blockade by successive bolus doses of vecuronium was recorded using electromyography. Inhibition of neuromuscular transmission by vecuronium was modeled by a biexponential decline in the concentrations in the central compartment and first-order transfer between the central and the effect compartments responsible for the inhibition of the first (T1) and fourth (T4) responses to train-of-four stimulation.

Results

The time course of the effect of vecuronium was described well by the model. The mean half-lives of equilibration between plasma and the effect compartments to inhibit T1 and T4 were 2.5 and 3.2 min, respectively. The mean half-lives of distribution and elimination from the central compartment were 7.7 and 7.8 min, respectively. From the kinetic and dynamic parameters calculated after two and three doses, the time taken to recover to 50% of the maximal block of T1 was predicted for the succeeding dose. The mean prediction errors (100 x [absolute difference between actual and predicted times]/actual) were 13.6% (range, 0-40%) and 15% (range, 0-25%) after three and four doses, respectively.

Conclusions

After sequential doses, measurement of the time course of the effect of vecuronium yields pharmacokinetic and pharmacodynamic parameters with clinically acceptable accuracy in individual patients.
Mood during Epidural Patient-controlled Analgesia with Morphine or Fentanyl
Authors: Tsueda Kentaro , Mosca Phillip J. , Heine Michael F. , Loyd Gary E. , Durkis Deirdre A. E. , Malkani Arthur L. , Hurst Harrell E.
Published: November 2003

Background

Mood states during epidural opioids are not known. The authors studied the change in mood during the 48-h period of epidural morphine and epidural fentanyl in 47 patients after elective hip or knee joint arthroplasty.

Methods

An epidural catheter was inserted at the L2-L3 or L3-L4 interspace. Anesthesia was induced with thiopenthal and maintained with isoflurane and nitrous oxide. One hour before the conclusion of the operation, patients received an epidural bolus injection of 2 mg morphine (n = 23) or 100 microg fentanyl (n = 24), followed by the same opiate (125 microg/ml morphine or 25 microg/ml fentanyl) epidurally delivered by a patient-controlled analgesia (PCA) pump in the postoperative period for 48 h. Mood was assessed using the bipolar form of the Profile of Mood States before operation and 24 h, 48 h, and 72 h after operation.

Results

There was no significant difference in pain intensity between the groups during epidural PCA. Mood states became more positive over time in the patients who received morphine (P < 0.01 at 48 h) and negative in those who were given fentanyl (P < 0.01 at 24 and 48 h, respectively) compared with those before the operation, and they were more positive in the morphine than in the fentanyl group at 24 h, 48 h (P < 0.05), and 72 h (P < 0.01). Patients in the morphine group were more composed, agreeable, elated, confident, energetic, and clearheaded than were those in the fentanyl group (P < 0.05). There was no correlation between mood scores and pain scores in either group. There was an inverse correlation at 48 h between mood scores and plasma fentanyl concentrations (r = -0.58, P < 0.05).

Conclusion

Mood states are significantly more positive during epidural morphine PCA than they are during epidural fentanyl PCA.
Changing from Isoflurane to Desflurane toward the End of Anesthesia Does Not Accelerate Recovery in Humans
Authors: Neumann Mireille A. , Weiskopf Richard B. , Gong Diane H. , Eger Edmond I , Ionescu Pompiliu
Published: November 2003

Background

In an attempt to combine the advantage of the lower solubilities of new inhaled anesthetics with the lesser cost of older anesthetics, some clinicians substitute the former for the latter toward the end of anesthesia. The authors tried to determine whether substituting desflurane for isoflurane in the last 30 min of a 120-min anesthetic would accelerate recovery.

Methods

Five volunteers were anesthetized three times for 2 h using a fresh gas inflow of 2 l/min: 1.25 minimum alveolar concentration (MAC) desflurane, 1.25 MAC isoflurane, and 1.25 MAC isoflurane for 90 min followed by 30 min of desflurane concentrations sufficient to achieve a total of 1.25 MAC equivalent ("crossover"). Recovery from anesthesia was assessed by the time to respond to commands, by orientation, and by tests of cognitive function.

Results

Compared with isoflurane, the crossover technique did not accelerate early or late recovery (P > 0.05). Recovery from isoflurane or the crossover anesthetic was significantly longer than after desflurane (P < 0.05). Times to response to commands for isoflurane, the crossover anesthetic, and desflurane were 23 +/- 5 min (mean +/- SD), 21 +/- 5 min, and 11 +/- 1 min, respectively, and to orientation the times were 27 +/- 7 min, 25 +/- 5 min, and 13 +/- 2 min, respectively. Cognitive test performance returned to reference values 15-30 min sooner after desflurane than after isoflurane or the crossover anesthetic. Isoflurane cognitive test performance did not differ from that with the crossover anesthetic at any time.

Conclusions

Substituting desflurane for isoflurane during the latter part of anesthesia does not improve recovery, in part because partial rebreathing through a semiclosed circuit limits elimination of isoflurane during the crossover period. Although higher fresh gas flow during the crossover period would speed isoflurane elimination, the amount of desflurane used and, therefore, the cost would increase.
Regional Cerebral Plasma Volume Response to Carbon Dioxide Using Magnetic Resonance Imaging
Authors: Payen Jean-Francois , Vath Albert , Koenigsberg Blanche , Bourlier Virginie , Decorps Michel
Published: November 2003

Background

Noninvasive techniques used to determine the changes in cerebral blood volume in response to carbon dioxide are hampered by their limited spatial or temporal resolution or both. Using steady state contrast-enhanced magnetic resonance imaging, the authors determined regional changes in cerebral plasma volume (CPV) induced by hypercapnia in halothane-anesthetized rats.

Methods

Cerebral plasma volume was determined during normocapnia, hypercapnia and recovery in the dorsoparietal neocortex and striatum of each hemisphere, in cerebellum, and in extracerebral tissue of rats with either intact carotid arteries (group 1) or unilateral common carotid ligation (group 2). Another group was studied without injection of a contrast agent (group 3).

Results

Hypercapnia (partial pressure of carbon dioxide in arterial blood [PaCO2] approximately 65 mmHg) resulted in a significant increase in CPV in the striatum (+42 +/- 8%), neocortex (+34 +/- 6%), and cerebellum (+49 +/- 12%) compared with normocapnic CPV values (group 1). Carotid ligation (group 2) led to a marked reduction of the CPV response to hypercapnia in the ipsilateral striatum (+23 +/- 14%) and neocortex (+27 +/- 17%) compared with the unclamped side (+34 +/- 15% and +38 +/- 16%, respectively). No significant changes in CPV were found in extracerebral tissue. In both groups, the CPV changes were reversed by the carbon dioxide washout period. Negligible changes in contrast imaging were detected during hypercapnia without administration of the contrast agent (group 3).

Conclusions

The contrast-enhanced magnetic resonance imaging technique is sensitive to detect noninvasively regional CPV changes induced by hypercapnia in rat brain. This could be of clinical interest for determining the cerebrovascular reactivity among different brain regions.
Effects of Volatile Anesthetic Agents on In Situ Vascular Smooth Muscle Transmembrane Potential in Resistance- and Capacitance-regulating Blood Vessels
Authors: Yamazaki Mitsuaki , Stekiel Thomas A. , Bosnjak Zeljko J. , Kampine John P. , Stekiel William J.
Published: November 2003

Introduction

This study was designed to compare the inhibitory effect of inhaled volatile anesthetic agents on in situ sympathetic neural versus nonneural regulation of vascular smooth muscle transmembrane potentials as correlates of vascular smooth muscle tone in resistance- and capacitance-regulating blood vessels.

Methods

Vascular smooth muscle transmembrane potentials were measured in situ with glass microelectrodes in neurally intact, small (200-300 m OD) mesenteric arteries and veins of rats before, during, and after inhaled halothane, isoflurane, or sevoflurane (0.5 or 1.0 minimum alveolar concentration [MAC]). Such transmembrane potentials and their anesthetically induced changes were compared, respectively, with those measured in similar vessel preparations after local sympathetic neural denervation with 6-hydroxydopamine.

Results

In neurally intact vessels, transmembrane potentials (in millivolts, mean +/- SD) before inhalation of the anesthetic agent were -39 +/- 2.8 (artery) and -43 +/- 4.6 (vein). At 1.0 MAC, halothane, isoflurane, and sevoflurane induced respective hyperpolarizations (in millivolts, mean +/- SD) of 9 +/- 3.1, 6 +/- 2.7, and 9 +/- 4.0 in arteries and 6 +/- 4.4, 2.8 +/- 3.0, and 8.7 +/- 5.6 in veins. Sympathetic denervation significantly attenuated these hyperpolarizations (except for venous response to isoflurane). At 0.5 MAC, transmembrane potential responses to all three volatile anesthetic agents were small and not consistently significant in either the intact or denervated vessels.

Conclusions

In resistance-regulating arteries in situ, inhaled halothane, isoflurane, and sevoflurane (1.0 MAC) attenuate both sympathetic neural and nonneural regulation of vascular smooth muscle transmembrane potentials (and tone). In capacitance-regulating veins in situ, sevoflurane (1.0 MAC) also attenuates both regulatory mechanisms, whereas halothane and isoflurane primarily attenuate nonneural mechanisms. At 0.5 MAC, none of these agents significantly affected either mode of regulation of vascular smooth muscle transmembrane potentials in arteries or veins.
Exposure to Environmental Tobacco Smoke and the Risk of Adverse Respiratory Events in Children Receiving General Anesthesia
Authors: Skolnick Eric T. , Vomvolakis Maria A. , Buck Karen A. , Mannino Salvatore F. , Sun Lena S.
Published: November 2003

Background

Exposure to environmental tobacco smoke is associated with detrimental effects on pulmonary function in children. The authors investigated the relation between airway complications in children receiving general anesthesia and the passive inhalation of tobacco smoke.

Methods

Six hundred two children scheduled to receive general anesthesia were enrolled in this prospective study. The anesthesiologist and the recovery room nurse, unaware of the smoke exposure history, recorded the occurrence of airway complications. A history of passive smoking was assessed by measuring the urinary concentration of the major nicotine metabolite cotinine and by questionnaire.

Results

Airway complications occurred in 42% of the patients with urinary concentrations of cotinine > or =40 ng/ml, in 33% of the patients with concentrations of cotinine between 10.0 and 39.9 ng/ml, and in 24% of the patients with concentrations of cotinine < 10 ng/ml (P = 0.01 for the trend among the three groups). The gender of the child (P = 0.001) and the educational level of the child's mother (P = 0.0008) significantly modified the effect of the concentration of cotinine on the incidence of adverse respiratory events.

Conclusions

There is a strong association between passive inhalation of tobacco smoke and airway complications in children receiving general anesthesia. The relationship is greatest for girls and for those whose mothers have a lower level of education. Passive smoking should be regarded as a risk factor in children undergoing general anesthesia.
The Influence of Method of Administration and Covariates on the Pharmacokinetics of Propofol in Adult Volunteers
Authors: Schnider Thomas W. , Minto Charles F. , Gambus Pedro L. , Andresen Corina , Goodale David B. , Shafer Steven L. , Youngs Elizabeth J.
Published: November 2003

Background

Unresolved issues with propofol include whether the pharmacokinetics are linear with dose, are influenced by method of administration (bolus vs. infusion), or are influenced by age. Recently, a new formulation of propofol emulsion, containing disodium edetate (EDTA), was introduced in the United States. Addition of EDTA was found by the manufacturer to significantly reduce bacterial growth. This study investigated the influences of method of administration, infusion rate, patient covariates, and EDTA on the pharmacokinetics of propofol.

Methods

Twenty-four healthy volunteers aged 26-81 yr were given a bolus dose of propofol, followed 1 h later by a 60-min infusion. Each volunteer was randomly assigned to an infusion rate of 25, 50, 100, or 200 microg x kg(-1) x min(-1). Each volunteer was studied twice under otherwise identical circumstances: once receiving propofol without EDTA and once receiving propofol with EDTA. The influence of the method of administration and of the volunteer covariates was explored by fitting a three-compartment mamillary model to the data. The influence of EDTA was investigated by direct comparison of the measured concentrations in both sessions.

Results

The concentrations of propofol with and without EDTA were not significantly different. The concentration measurements after the bolus dose were significantly underpredicted by the parameters obtained just from the infusion data. The kinetics of propofol were linear within the infusion range of 25-200 microg x kg(-1) x min(-1). Age was a significant covariate for Volume2 and Clearance2, as were weight, height, and lean body mass for the metabolic clearance.

Conclusions

These results demonstrate that method of administration (bolus vs. infusion), but not EDTA, influences the pharmacokinetics of propofol. Within the clinically relevant range, the kinetics of propofol during infusions are linear regarding infusion rate.
Pulsed Doppler Ultrasonography Guidance for Catheterization of the Subclavian Vein
Authors: Lefrant Jean-Yves , Cuvillon Philippe , Benezet Jean-Francois , Dauzat Michel , Peray Pascale , Saissi Gilbert , de La Coussaye Jean-Emmanuel , Eledjam Jean-Jacques
Published: November 2003

Background

Catheterization of the subclavian vein may lead to severe complications. The current randomized study compared a technique of pulsed Doppler ultrasonography guidance and the standard method for subclavian vein catheterization.

Methods

Standard and Doppler ultrasonography guidance methods were performed by the same physician in 286 patients, 143 in each group. Primary end points were immediate complications (arterial puncture, pneumothorax, wrong position of catheter tip), failures, the number of subclavian vein catheterizations with immediate complication or failure, the number of skin punctures per catheterization, and the time to placement of the guide wire. The secondary end points were the determination of predicting factors of successful cannulation in each group.

Results

Both groups were similar according to morphologic parameters of the patients. A greater number of subclavian vein catheterizations were performed on the right side using Doppler guidance (105 vs. 73, P < 0.01). Doppler guidance decreased complications (5.6% vs. 16.8%, P < 0.01), largely because of a smaller number of catheters for which the tip was defined to be in incorrect position (0.7% vs. 7.7%, P < 0.01). The time to catheterization was longer with Doppler guidance (300 vs. 27 s, P < 0.001). Failures, catheterizations of the subclavian vein with immediate complications or failure, and the total number of skin punctures per catheterization were similar in both groups. Using Doppler guidance, the presence of a good Doppler signal (124 of 143) was predictive of successful catheterization (123 successful cannulations, P < 0.001).

Conclusions

Doppler guidance reduces the incidence of inappropriately positioned subclavian catheters.
Metabolic Changes during Recovery in Normothermic versus Hypothermic Patients Undergoing Surgery and Receiving General Anesthesia and Epidural Local Anesthetic Agents
Authors: Motamed Syrusse , Klubien Kristine , Edwardes Michael , Mazza Louise , Carli Franco
Published: November 2003

Background

Mild hypothermia is accompanied by metabolic changes. Epidural local anesthetic agents attenuate the surgical stress response, but it is not known whether they modulate thermal stress.

Methods

Thirty patients undergoing colorectal surgery, performed by one surgical team, received epidural 0.5% bupivacaine to achieve T3-S5 sensory block. They were then assigned randomly to two groups of 15 patients each. The control or unwarmed group was left to cool during surgery, whereas active warming was used in the warmed group. General anesthesia was induced by thiopentone, vecuronium, fentanyl, nitrous oxide in oxygen, and enflurane. At the end of surgery, both groups received epidural 0.25% bupivacaine to maintain a T5-L3 sensory block. Aural canal (core) and skin surface (15 sites) temperatures; oxygen consumption; pain visual analogue score; and concentrations of epinephrine, norepinephrine, glucose, cortisol, lactate, and free fatty acids in plasma were measured before epidural blockade, 30 min after epidural blockade, at the end of surgery, and for 4 h after surgery. Patients and those measuring the outcomes were unaware of group allocation.

Results

Core and mean skin temperatures decreased significantly in the control group (P < 0.001) but not in the warmed group. Catecholamine concentrations in plasma decreased significantly after epidural block, and although concentration of epinephrine in plasma increased from baseline sharply in the control group at the end of surgery (P = 0.004), it decreased in the warmed group (P = 0.007). During recovery, there was no difference between the two groups for norepinephrine concentrations in plasma, body weight-adjusted oxygen consumption, pain visual analogue score, and metabolites.

Conclusions

The postoperative metabolic changes obtained with epidural block were similar except for an attenuated concentration of epinephrine in normothermic patients compared with those who were mildly hypothermic.
Desflurane-mediated Sympathetic Activation Occurs in Humans Despite Preventing Hypotension and Baroreceptor Unloading
Authors: Ebert Thomas J. , Perez Francisco , Uhrich Toni D. , Deshur Mark A.
Published: November 2003

Background

Increasing concentrations of desflurane result in progressive decreases in blood pressure (BP) and, unlike other currently marketed, potent volatile anesthetics, heightened sympathetic nervous system activity. This study aimed to determine whether baroreflex mechanisms are involved in desflurane-mediated sympathetic excitation.

Methods

Healthy volunteers were anesthetized with desflurane (n = 8) or isoflurane (n = 9). Heart rate (HR; measured by electrocardiograph), blood pressure (BP; measured by arterial catheter), and efferent sympathetic nerve activity (SNA; obtained from percutaneous recordings from the peroneal nerve) were monitored. Baroreflex sensitivity was evaluated at baseline while volunteers were conscious and during 0.5, 1, and 1.5 minimum alveolar concentration (MAC) anesthesia via bolus injections of nitroprusside (100 microg) and phenylephrine (150 microg) to decrease and increase BP. To prevent the BP decline with increasing depths of anesthesia, phenylephrine was infused to maintain mean BP at the 0.5 MAC level.

Results

The HR, BP, and SNA were similar between the groups at the conscious baseline measurement. Efferent SNA did not change during higher MAC of isoflurane, but it increased progressively as desflurane concentrations were increased beyond 0.5 MAC, despite maintaining BP at the 0.5 MAC value with phenylephrine infusions (P < 0.05). Cardiac baroslopes (based on changes in HR) were progressively and similarly decreased with increasing concentrations of isoflurane and desflurane (P < 0.05). Sympathetic baroslopes (based on SNA) decreased with increasing isoflurane concentrations but were maintained with increasing concentrations of desflurane; the response was significantly different between groups.

Conclusions

The increase in basal levels of SNA with increasing concentrations of desflurane persisted despite "fixing" BP and thus is probably not due to hypotension and unloading of the baroreceptors. Further, the preservation of reflex increases in SNA to nitroprusside during desflurane indicates that desflurane preserves one component of the baroreflex in humans when BP is "fixed."
Dobutamine Stress Echocardiography to Detect Inducible Demand Ischemia in Anesthetized Patients with Coronary Artery Disease
Authors: Seeberger Manfred D. , Skarvan Karl , Buser Peter , Brett Wolfgang , Rohlfs Reinhard , Erne Jean-Jacques , Rosenthaler Cyril , Pfisterer Matthias , Atar Dan
Published: November 2003

Background

A cardiac risk stratification test that can be performed during operation would be expected to give valuable information for the therapeutic management of patients who need urgent noncardiac surgery. This study was designed to evaluate the feasibility and safety of a dobutamine-atropine stress protocol to detect inducible demand ischemia in anesthetized patients.

Methods

A standard dobutamine-atropine stress protocol was performed in 80 patients with severe coronary artery disease during fentanyl-isoflurane anesthesia. Biplane transesophageal echocardiography and 12-lead electrocardiography were used to detect induced ischemia. After dobutamine testing, esmolol, nitroglycerin, or both were used to revert ischemia and any hemodynamic changes, as appropriate.

Results

The protocol detected inducible ischemia or achieved the target heart rate in 75 of the 80 (94%) patients. None of the prospectively defined adverse outcomes, such as cardiovascular collapse, severe ventricular arrhythmia, persistent (> or =5 min) ischemia, or hemodynamic instability, occurred in any of the patients. Ischemia was induced and detected in 73 of the 80 (91%) patients.

Conclusion

Dobutamine stress echocardiography is feasible in anesthetized patients with severe coronary artery disease. The lack of serious complications and the high sensitivity to detect inducible ischemia in this patient population provide the basis for further evaluation of the safety and diagnostic value of dobutamine stress echocardiography during general anesthesia in larger studies of patients at risk for coronary artery disease undergoing noncardiac surgery.
Pulmonary Blood Flow Redistribution with Low Levels of Positive End-expiratory Pressure
Authors: Kallas Harry J. , Domino Karen B. , Glenny Robb W. , Anderson Emily A. , Hlastala Michael P.
Published: November 2003

Background

Recent studies have questioned the importance of the gravitational model of pulmonary perfusion. Because low levels of positive end-expiratory pressure (PEEP) are commonly used during anesthesia, the authors studied the distribution of pulmonary blood flow with low levels of PEEP using a high spatial resolution technique. They hypothesized that if hydrostatic factors were important in the distribution of pulmonary blood flow, PEEP would redistribute flow to more dependent lung regions.

Methods

The effects of zero cm H2O PEEP and 5 cm H2O PEEP on pulmonary gas exchange were studied using the multiple inert gas elimination technique; the distribution of pulmonary blood flow, using fluorescent-labeled microspheres, was also investigated in mechanically ventilated, pentobarbital-anesthetized dogs. The lungs were removed, cleared of blood, dried at total lung capacity, and then cubed to obtain approximately 1,000 small pieces of lung (approximately 1.7 cm3).

Results

Positive end-expiratory pressure increased the partial pressure of oxygen by 6 +/- 2 mmHg (P < 0.05) and reduced all measures of ventilation and perfusion heterogeneity (P < 0.05). By reducing flow to nondependent ventral lung regions and increasing flow to dependent dorsal lung regions, PEEP increased (P < 0.05) the dorsal-to-ventral gradient. Redistribution of blood flow with PEEP accounted for 7 +/- 3%, whereas structural factors accounted for 93 +/- 3% of the total variance in blood flow.

Conclusions

The increase in dependent-to-nondependent gradient with PEEP is partially consistent with the gravitationally based lung zone model. However, the results emphasize the greater importance of anatomic factors in determining the distribution of pulmonary blood flow.
Comparison of the Effects of Bupivacaine and Ropivacaine on Heart Cell Mitochondrial Bioenergetics
Authors: Sztark Francois , Malgat Monique , Dabadie Philippe , Mazat Jean-Pierre
Published: November 2003

Background

High lipophilic local anesthetics interfere with mitochondrial energy metabolism. These metabolic effects could in part explain some of the toxic effects of local anesthetics, such as bupivacaine-induced myocardial depression. The aim of this study was to compare the bioenergetic effects of the local anesthetics bupivacaine and ropivacaine.

Methods

The effects of both local anesthetics on mitochondrial energy metabolism were studied in rat heart isolated mitochondria and in saponin-skinned left ventricle fibers. Oxygen consumption, adenosine triphosphate synthesis, and enzymatic activities of the complexes of the respiratory chain were measured.

Results

Bupivacaine and ropivacaine acted, in isolated mitochondria, as uncouplers between oxygen consumption and phosphorylation of adenosine diphosphate. Further, an inhibitory effect of mitochondrial respiration was evidenced with both anesthetics during maximal respiration and was assigned to a direct inhibition of complex I of the respiratory chain. Mitochondrial adenosine triphosphate synthesis was decreased by both mechanisms. However, both in isolated mitochondria and in permeabilized heart fibers, ropivacaine was less potent than bupivacaine. Adenosine triphosphate synthesis was completely suppressed at 3 mM (approximately 0.1%) bupivacaine, whereas 3 mM ropivacaine induced only about a 40% inhibition.

Conclusions

Ropivacaine disturbs mitochondrial energy metabolism less than bupivacaine does. The lower lipid solubility of ropivacaine may be responsible for the lesser dose-dependent effects of this drug on mitochondrial bioenergetics.
Upper Airway Reflexes during a Combination of Propofol and Fentanyl Anesthesia
Authors: Tagaito Yugo , Isono Shiroh , Nishino Takashi
Published: November 2003

Background

The effects of intravenous anesthetics on airway protective reflexes have not been fully explored. The purpose of the present study was to characterize respiratory and laryngeal responses to laryngeal irritation during increasing doses of fentanyl under propofol anesthesia.

Methods

Twenty-two female patients anesthetized with propofol and breathing through the laryngeal mask airway were randomly allocated to three groups: (1) eight patients who received cumulative total doses of 200 microg fentanyl given in the form of two doses of 50 microg and one dose of 100 microg spaced 6 min under mechanical controlled ventilation while end-tidal carbon dioxide tension (PCO2) was maintained at 38 mmHg (fentanyl-controlled ventilation group), (2) eight patients who received cumulative total doses of 200 microg fentanyl while breathing spontaneously while end-tidal PCO2 was allowed to increase spontaneously (fentanyl-spontaneous ventilation group), and (3) six spontaneously breathing patients who were anesthetized with propofol alone (propofol group). The laryngeal mucosa of each patient was stimulated by spraying the cord with distilled water, and the evoked responses were assessed by analyzing the respiratory variables and endoscopic images.

Results

Before administration of fentanyl, laryngeal stimulation caused vigorous reflex responses, such as expiration reflex spasmodic panting, cough reflex, and apnea with laryngospasm. Increasing doses of fentanyl reduced the incidences of all these responses, except for apnea with laryngospasm, in a dose-related manner in both the fentanyl-controlled ventilation and the fentanyl-spontaneous ventilation groups. Detailed analysis of endoscopic images revealed several characteristics of laryngeal behavior during the airway reflex responses.

Conclusion

Incremental doses of fentanyl depress airway reflex responses in a dose-related manner, except for apnea with laryngospasm.
Dobutamine Antagonizes Epinephrine's Biochemical and Cardiotonic Effects
Authors: Prielipp Richard C. , MacGregor Drew A. , Royster Roger L. , Kon Neal D. , Hines Michael H. , Butterworth John F.
Published: November 2003

Background

Patients may receive more than one positive inotropic drug to improve myocardial function and cardiac output, with the assumption that the effects of two drugs are additive. The authors hypothesized that combinations of dobutamine and epinephrine would produce additive biochemical and hemodynamic effects.

Methods

The study was performed in two parts. Phase 1 used human lymphocytes in an in vitro model of cyclic adenosine monophosphate (cAMP) generation in response to dobutamine (10(-8) to 10(-4) M) or epinephrine (10(-9) M to 10(-5) M), and dobutamine and epinephrine together. Phase 2 was a clinical study in patients after aortocoronary artery bypass in which isobolographic analysis compared the cardiotonic effects of dobutamine (1.25, 2.5, or 5 microg x kg(-1) x min(-1)) or epinephrine (10, 20, or 40 ng x kg(-l) x min(-1)), alone or in combination.

Results

In phase 1, dobutamine increased cAMP production 41%, whereas epinephrine increased cAMP concentration approximately 200%. However, when epinephrine (10(-6) M) and dobutamine were combined, dobutamine reduced cAMP production at concentrations between 10(-6) to 10(-4) M (P = 0.001). In patients, 1.25 to 5 microg x kg(-1) x min(-1) dobutamine increased the cardiac index (CI) 15-28%. Epinephrine also increased the CI with each increase in dose. However, combining epinephrine with the two larger doses of dobutamine (2.5 and 5microg x kg(-1) x mi(-1)) did not increase the CI beyond that achieved with epinephrine and the lowest dose of dobutamine (1.25 microg x kg(-1) x min(-1)). In addition, the isobolographic analysis for equieffective concentrations of dobutamine and epinephrine suggests subadditive effects.

Conclusions

Dobutamine inhibits epinephrine-induced production of cAMP in human lymphocytes and appears to be subadditive by clinical and isobolographic analyses of the cardiotonic effects. These findings suggest that combinations of dobutamine and epinephrine may be less than additive.
Peripheral Analgesic Effects of Ketamine in Acute Inflammatory Pain
Authors: Pedersen Juri L. , Galle Tina S. , Kehlet Henrik
Published: November 2003

Unlabelled

BACKGROUND. This study examined the analgesic effect of local ketamine infiltration, compared with placebo and systemic ketamine, in a human model of inflammatory pain.

Methods

Inflammatory pain was induced by a burn (at 47 degrees C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteers on 3 separate days with 7-day intervals. They received either (1) subcutaneous infiltration with ketamine in the burn area (local treatment) and contralateral placebo injections, or (2) subcutaneous ketamine contralateral to the burn (systemic treatment) and placebo in the burn area, or (3) placebo on both sides. The study was double-blinded and the order of the treatments was randomized. Hyperalgesia to mechanical and heat stimuli was examined by von Frey hairs and contact thermodes (3.75 and 12.5 cm2), and pain was rated using a visual analog scale (0-100).

Results

The burns produced significant hyperalgesia. Local ketamine infiltration reduced pain during the burn injury compared with systemic treatment and placebo (P < 0.01). Heat pain thresholds were increased by local ketamine treatment compared with placebo immediately after injection (P < 0.03), and so were the mechanical pain thresholds (P = 0.02). Secondary hyperalgesia and suprathreshold pain responses to heat and mechanical stimuli were not significantly affected by local ketamine. No difference between local ketamine and placebo could be detected 1 h and 2 h after the burn.

Conclusions

Ketamine infiltration had brief local analgesic effects, but several measures of pain and hyperalgesia were unaffected. Therefore, a clinically relevant effect of peripheral ketamine in acute pain seems unlikely.