bluuebunny/crossref_metadata_2025 huggingface dataset:
Variability in Surgical Caseload and Access to Intensive Care Services
Authors: McManus Michael L. , Long Michael C. , Cooper Abbot , Mandell James , Berwick Donald M. , Pagano Marcello , Litvak Eugene
Published: November 2003

Background

Variability in the demand for any service is a significant barrier to efficient distribution of limited resources. In health care, demand is often highly variable and access may be limited when peaks cannot be accommodated in a downsized care delivery system. Intensive care units may frequently present bottlenecks to patient flow, and saturation of these services limits a hospital's responsiveness to new emergencies.

Methods

Over a 1-yr period, information was collected prospectively on all requests for admission to the intensive care unit of a large, urban children's hospital. Data included the nature of each request, as well as each patient's final disposition. The daily variability of requests was then analyzed and related to the unit's ability to accommodate new admissions.

Results

Day-to-day demand for intensive care services was extremely variable. This variability was particularly high among patients undergoing scheduled surgical procedures, with variability of scheduled admissions exceeding that of emergencies. Peaks of demand were associated with diversion of patients both within the hospital (to off-service care sites) and to other institutions (ambulance diversions). Although emergency requests for admission outnumbered scheduled requests, diversion from the intensive care unit was better correlated with scheduled caseload (r = 0.542, P < 0.001) than with unscheduled volume (r = 0.255, P < 0.001). During the busiest periods, nearly 70% of all diversions were associated with variability in the scheduled caseload.

Conclusions

Variability in scheduled surgical caseload represents a potentially reducible source of stress on intensive care units in hospitals and throughout the healthcare delivery system generally. When uncontrolled, variability limits access to care and impairs overall responsiveness to emergencies.
Effect of Prophylactic Bronchodilator Treatment with Intravenous Colforsin Daropate, a Water-soluble Forskolin Derivative, on Airway Resistance after Tracheal Intubation
Authors: Wajima Zen'ichiro , Shiga Toshiya , Yoshikawa Tatsusuke , Ogura Akira , Imanaga Kazuyuki , Inoue Tetsuo , Ogawa Ryo
Published: November 2003

Background

After induction of anesthesia, lung resistance increases. The authors hypothesized that prophylactic bronchodilator treatment with intravenous colforsin daropate, a water-soluble forskolin derivative, before tracheal intubation would result in decreased lung resistance and increased lung compliance after tracheal intubation when compared with placebo medication.

Methods

Forty-six adult patients were randomized to placebo or colforsin daropate treatment. Patients in the control group received normal saline; patients in the colforsin group received 0.75 microg. kg-1 x min-1 colforsin daropate intravenously until the study ended. Thirty minutes after the study began, the authors administered 5 mg/kg thiamylal and 5 microg/kg fentanyl for induction of general anesthesia and 0.3 mg/kg vecuronium for muscle relaxation. A 15-mg. kg-1. h-1 continuous infusion of thiamylal followed anesthetic induction. Four, 8, 12, and 16 min after tracheal intubation, mean airway resistance (R(awm)), expiratory airway resistance (R(awe)), and dynamic lung compliance (C(dyn)) were measured.

Results

Patients in the colforsin group had significantly lower R(awm) and R(awe) and higher C(dyn) after intubation than those in the control group. Differences in R(awm), R(awe), and C(dyn) between the two groups persisted through the final measurement at 16 min. At 4 min after intubation, smokers had a higher R(awm) and a lower C(dyn) than nonsmokers in the control group. After treatment by intravenous colforsin daropate, R(awm), R(awe), and C(dyn) values were similar for smokers and nonsmokers after tracheal intubation.

Conclusions

Prophylactic treatment with colforsin daropate produced lower R(awm) and R(awe) and higher C(dyn) after tracheal intubation when compared with placebo medication. Pretreatment before intubation may be beneficial and advantageous for middle-aged smokers.
Relationship between Aortic-to-radial Arterial Pressure Gradient after Cardiopulmonary Bypass and Changes in Arterial Elasticity
Authors: Kanazawa Masahiro , Fukuyama Haruo , Kinefuchi Yoshio , Takiguchi Mamoru , Suzuki Toshiyasu
Published: November 2003

Background

An aortic-to-radial arterial pressure gradient may develop during and after cardiopulmonary bypass (CPB). The mechanisms of this pressure gradient remain controversial. To clarify the cause of the pressure gradient after CPB, the authors investigated the relationship between the pressure gradient and changes in the pulse wave velocity (PWV) before and after CPB.

Methods

The pressure gradient from the aorta to the radial artery and a change in PWV were measured with a wire (0.37 mm in diameter) tipped with a miniature pressure transducer in 12 patients undergoing cardiac surgery. The pressure distributions and waveforms were measured and recorded with electrocardiograph. The PWV was calculated by measuring the propagation time between the R wave of the electrocardiograph and the rising point of the arterial pressure waveform at 10-cm intervals.

Results

After CPB, 7 of 12 patients demonstrated a marked pressure gradient. In these patients, the pressure distribution showed a gradual decrease toward the periphery without a precipitous step-down in pressure at any one specific anatomic location. The PWV decreased as the intraarterial pressure decreased from the aorta to the radial artery, and the relative arterial elasticity decreased linearly toward the periphery.

Conclusions

The results showed that the decrease in PWV implies a decrease in arterial elasticity, and the decrease in the arterial elasticity correlated with the decrease in intraarterial pressure. These findings demonstrated that a radial artery pressure lower than the aortic pressure after CPB may be due to the decrease in arterial elasticity.
Cricoid Pressure Displaces the Esophagus: An Observational Study Using Magnetic Resonance Imaging
Authors: Smith Kevin J. , Dobranowski Julian , Yip Gordon , Dauphin Alezandre , Choi Peter T-L.
Published: November 2003

Background

Cricoid pressure (CP) is often used during general anesthesia induction to prevent passive regurgitation of gastric contents. The authors used magnetic resonance imaging to determine the anatomic relationship between the esophagus and the cricoid cartilage ("cricoid") with and without CP.

Methods

Magnetic resonance images of the necks of 22 healthy volunteers were reviewed with and without CP. Esophageal and airway dimensions, distance between the midline of the vertebral body and the midline of the esophagus, and distance between the lateral border of the cricoid or vertebral body and the lateral border of the esophagus were measured.

Results

The esophagus was displaced laterally relative to the cricoid in 52.6% of necks without CP and 90.5% with CP. CP shifted the esophagus relative to its initial position to the left in 68.4% of subjects and to the right in 21.1% of subjects. Unopposed esophagus was seen in 47.4% of necks without CP and 71.4% with CP. Lateral laryngeal displacement and airway compression were demonstrated in 66.7% and 81.0% of necks, respectively, as a result of CP.

Conclusion

In the absence of CP, the esophagus was lateral to the cricoid in more than 50% of the sample. CP further displaced both the esophagus and the larynx laterally.
Systemically Administered α2-Agonist-induced Peripheral Vasoconstriction in Humans
Authors: Talke Pekka , Lobo Errol , Brown Ronald
Published: November 2003

Background

alpha(2)-Adrenoceptors mediate both sympatholytic and vasoconstrictive hemodynamic effects. The goal of this study was to profile the peripheral vasoconstrictive effects of a selective alpha(2)-adrenoceptor agonist in isolation from the sympatholytic effects it also induces.

Methods

The authors administered increasing plasma target concentrations of dexmedetomidine (0.075, 0.15, 0.3, and 0.6 ng/mL) or saline placebo to healthy young volunteers in whom the sympatholytic effects of the drug were attenuated in one of two ways: general anesthesia (propofol-alfentanil-nitrous oxide) or axillary brachial plexus block. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmitted through a finger (LTF) and hemodynamic variables. Measurements made before and during the four steps of infusion were compared by repeated-measures ANOVA.

Results

In anesthetized volunteers, all concentrations of dexmedetomidine increased LTF (vasoconstriction) and systolic blood pressure (P < 0.001 for both), whereas placebo did not. In awake volunteers, all concentrations decreased systolic blood pressure (P < 0.001). Concentrations of 0.15, 0.3, and 0.6 ng/mL decreased LTF (vasodilation) in the neurally intact hand; in contrast, the same concentrations increased LTF (vasoconstriction) in the sympathectomized hand (P < 0.001 for both).

Conclusions

The results of this study are the first to characterize the lower end of the dose-response curve for vasoconstriction induced by dexmedetomidine. By denervating the vascular bed of interest or by decreasing sympathetic nervous system activity, the authors were able to observe vasoconstriction induced by a systemically administered alpha(2)-agonist with minimal interference from the sympatholytic effects of the drug.
Effects of Inhalational Anesthetics on L-type Ca2+Currents in Human Atrial Cardiomyocytes during β-Adrenergic Stimulation
Authors: Fassl Jens , Halaszovich Christian R. , Hüneke Rocco , Jüngling Eberhard , Rossaint Rolf , Lückhoff Andreas
Published: November 2003

Background

Anesthetics may cause cardiac side effects by their action on L-type Ca2+ channels. Direct effects on the channels have not yet been discriminated from an interference with the beta-adrenergic channel regulation. The authors therefore studied the effects of halothane, sevoflurane, and xenon on human cardiac Ca2+ currents during stimulation with isoproterenol.

Methods

Currents through L-type Ca2+ channels were measured with the patch clamp technique in atrial cardiomyocytes obtained from patients undergoing cardiac surgery. Cells were superfused with solutions equilibrated with anesthetics at the desired concentrations. Ca2+ currents during pulses to 10 mV were evaluated with respect to their peak value (I(max)) and to the total moved charge (Q).

Results

In the absence and in the presence of isoproterenol (1 microm), sevoflurane (0.29 mm, 1 minimum alveolar concentration [MAC]) significantly depressed Q by 37.8 +/- 7.2% (mean +/- SD) and 40.8 +/- 10.3%, respectively. I(max) was not significantly affected in comparison with control cells never exposed to an anesthetic. Xenon (65%, 1 MAC) did not evoke significant effects. Exposure to halothane (0.39 mm, 1 MAC) during stimulation with isoproterenol significantly reduced Q by 31.3 +/- 23.3% (but not I(max)). After washout of halothane, Q was increased above the level prior to the application of halothane. Moreover, whereas Q promptly declined to baseline levels after washout of isoproterenol in controls, the previous exposure to halothane markedly delayed this decline, leaving Q significantly elevated for several minutes.

Conclusions

Halothane exerts a dual effect on Ca2+ currents. The long-lasting stimulatory effect may contribute to the proarrhythmic potency of the drug that exceeds that of sevoflurane, which only depressed Ca2+ currents.
Improved Resuscitation after Cardiac Arrest in Rats Expressing the Baculovirus Caspase Inhibitor Protein p35 in Central Neurons
Authors: Vogel Peter , Putten Herman v.d. , Popp Erik , Krumnikl Jakub J. , Teschendorf Peter , Galmbacher Roland , Kisielow Malgorzata , Wiessner Christoph , Schmitz Albert , Tomaselli Kevin J. , Schmitz Bernd , Martin Eike , Böttiger Bernd W.
Published: November 2003

Background

Global cerebral ischemia is associated with delayed neuronal death. Given the role of caspases in apoptosis, caspase inhibitors may provide neuronal protection after cardiac arrest. To this end, the authors generated a transgenic rat line expressing baculovirus p35, a broad-spectrum caspase inhibitor, in central neurons. Its effects were evaluated on neuronal cell death and outcome after global cerebral ischemia.

Methods

Global cerebral ischemia was induced by cardiocirculatory arrest. After 6 min, animals were resuscitated by controlled ventilation, extrathoracic cardiac massage, epinephrine, and electrical countershocks. Neuronal death was assessed after 7 days by histologic evaluation of the hippocampal cornu ammonis 1 sector. Postischemic outcome was assessed by determination of overall survival and according to neurologic deficit scores 24 h, 3 days, and 7 days after resuscitation.

Results

The rate of 7-day survival after cardiac arrest for the transgenic rats (85%) was significantly higher than that for the nontransgenic controls (52%; P < 0.05). However, no differences were observed either in the number of terminal deoxynucleotidyltransferase-mediated d-uracil triphosphate-biotin nick end-labeling-positive cells or viable neurons in the cornu ammonis 1 sector or in the neurologic deficit score when comparing surviving transgenic and nontransgenic rats. These findings suggest that neuronal apoptosis after cardiac arrest is not primarily initiated by activation of caspases.

Conclusion

Expression of baculovirus p35 can improve survival after cardiac arrest in rats, but the mode and site of action remain to be elucidated.
Differential Uptake of Volatile Agents into Brain Tissue In Vitro
Authors: Chesney Michael A. , Perouansky Misha , Pearce Robert A.
Published: November 2003

Background

The rate of onset of drug actions in experiments with brain slices in vitro can vary widely. One factor that influences the rate is access to tissue sites of action. To study the effects of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, also termed 2N in the literature) on physiologic processes under defined tissue concentrations, the authors performed electrophysiologic measurements of the effects of F6 and halothane, measured the uptake of these agents into brain tissue, and performed computational modeling to determine concentration-depth profiles during drug application.

Methods

Hippocampal brain slices 500 microm thick were prepared from adult rats. Evoked population responses in the CA1 region were obtained using extracellular recordings and electrical stimulation of the Schaffer collateral pathway. F6 (24 microm) and halothane (270 microm) were applied via superfusion for 40 min. Uptake of drug into tissue slices was measured using gas chromatography. Computational modeling was used to obtain estimates of drug diffusion coefficients in brain tissue and to calculate tissue concentration as a function of time and depth during drug application.

Results

Halothane reduced the amplitude of the evoked population spike and reduced the population excitatory postsynaptic potential slope. F6 had no effect on either measure. Uptake experiments yielded a diffusion coefficient of 0.1 x 10-6 cm2/s for F6 and 0.8 x 10-6 cm2/s for halothane. After 40 min of drug application, the concentration reached at tissue depths from which physiologic signals were obtained, approximately the top 200 microm of the slice, was estimated to be 58% of the final equilibrium value for F6 and 93% for halothane.

Conclusions

Diffusion into tissue is substantially slower for F6 than for halothane, and its impact is great enough that this must be considered when designing or interpreting in vitro experiments. However, impaired access does not account for the lack of effect of F6 on electrophysiologic responses in rat hippocampal slices.
Postoperative Morphine Consumption in the Elderly Patient
Authors: Aubrun Frédéric , Bunge Dorothea , Langeron Olivier , Saillant Gérard , Coriat Pierre , Riou Bruno
Published: November 2003

Background

It has been suggested that the dose of intravenous morphine used during postoperative titration is not modified by aging. The authors therefore studied morphine requirements in patients undergoing total hip replacement.

Methods

Intravenous morphine titration was administered as boluses, then subcutaneous morphine was administered every 4 h over 24 h. Pain was assessed by use of the visual analog scale (0 to 100), and the threshold required to administer morphine was 30. Young and elderly (> or =70 yr old) patients were compared. Data are mean +/- SD or odds ratio (OR) [95% CI].

Results

Two hundred twenty-four patients (68%) were young and 105 (32%) were elderly. The initial visual analog scale was not significantly different between groups. The dose of intravenous morphine in the postanesthesia care unit was not significantly different between young and elderly patients (0.15 +/- 0.11 vs. 0.14 +/- 0.10 mg/kg, P = NS), in contrast to the dose of subcutaneous morphine (0.18 +/- 0.18 vs. 0.11 +/- 0.11 mg/kg, P < 0.001) in the ward. Only severe pain (visual analog scale of 70 or greater; OR, 10.5 [4.5-24.8]) was significantly associated with a high dose (greater than 0.15 mg/kg) of intravenous morphine, whereas severe pain (OR, 2.5 [1.6-4.0]), age less than 60 yr (OR, 2.3 [1.4-3.8]), and absence of a nonsteroidal antiinflammatory drug (OR, 1.9 [1.2-3.1]) were significantly associated with a high dose (greater than 0.12 mg/kg) of subcutaneous morphine.

Conclusions

The dose of intravenous morphine during titration is not modified in elderly patients, in contrast to the dose administered subcutaneously over a prolonged period.
Cephalad Movement of Morphine and Fentanyl in Humans after Intrathecal Injection
Authors: Eisenach James C. , Hood David D. , Curry Regina , Shafer Steven L.
Published: November 2003

Background

Despite decades of use, controversy remains regarding the extent and time course of cephalad spread of opioids in cerebrospinal fluid (CSF) after intrathecal injection. The purpose of this study was to examine differences between two often used opioids, morphine and fentanyl, in distribution in the CSF after intrathecal injection.

Methods

Eight healthy volunteers received intrathecal injection of morphine (50 microg) plus fentanyl (50 microg) at a lower lumbar interspace. CSF was sampled through a needle in an upper lumbar interspace for 60-120 min. At the end of this time, a sample was taken from the lower lumbar needle, and both needles were withdrawn. CSF volume was determined by magnetic resonance imaging. Pharmacokinetic modeling was performed with NONMEM.

Results

Morphine and fentanyl peaked in CSF at the cephalad needle at similar times (41 +/- 13 min for fentanyl, 57 +/- 12 min for morphine). The ratio of morphine to fentanyl in CSF at the cephalad needle increased with time, surpassing 2:1 by 36 min and 4:1 by 103 min. CSF concentrations did not correlate with weight, height, or lumbosacral CSF volume. The concentrations of morphine and fentanyl at both sampling sites were well described by a simple pharmacokinetic model. The individual model parameters did not correlate with the distance between the needles, CSF volume, patient height, or patient weight.

Conclusions

Fentanyl is cleared more rapidly from CSF than morphine, although their initial distribution in the first hour after injection does not differ greatly. The pharmacokinetic model demonstrates that mixing is the primary determinant of early concentrations and is highly variable among individuals.
Predictors of Survival following Cardiac Arrest in Patients Undergoing Noncardiac Surgery
Authors: Sprung Juraj , Warner Mary E. , Contreras Michael G. , Schroeder Darrell R. , Beighley Christopher M. , Wilson Gregory A. , Warner David O.
Published: November 2003

Background

The authors determined the incidence of cardiac arrest and predictors of survival following perioperative cardiac arrest in a large population of patients at a tertiary referral center.

Methods

Medical records of patients who experienced cardiac arrest in the perioperative period surrounding noncardiac surgery between January 1, 1990, and December 31, 2000, were reviewed. Logistic regression identified characteristics associated with immediate (>or= 1 h) and hospital survival, with P <or= 0.01 considered statistically significant.

Results

Cardiac arrest occurred in 223 of 518,294 anesthetics (4.3 per 10,000) during the study period. Frequency of arrest for patients receiving general anesthesia decreased over time (7.8 per 10,000 during 1990-1992; 3.2 per 10,000 during 1998-2000). The frequency of arrest during regional anesthesia (1.5 per 10,000) and monitored anesthesia care (0.7 per 10,000) remained consistent. Immediate survival after arrest was 46.6%, and hospital survival was 34.5%. Twenty-four patients (0.5 per 10,000) had cardiac arrest related primarily to anesthesia. From multivariate analysis, patients who experienced arrest due to bleeding were less likely to survive hospitalization (P = 0.001). Survival was also lower for patients who experienced arrest during nonstandard working hours (P = 0.006) and for patients who had protracted hypotension before arrest (P < 0.001).

Conclusions

The overall frequency of arrest for patients receiving anesthesia decreased during the study period. Most arrests were not due to anesthesia-related causes, and most patients experiencing anesthesia-related arrest survived to hospital discharge. Although many factors determining survival may not be amenable to modification, the fact that arrests during nonregular working hours had worse outcomes may indicate that the availability of human resources influences survival.
Effects of Propofol, Desflurane, and Sevoflurane on Recovery of Myocardial Function after Coronary Surgery in Elderly High-risk Patients
Authors: De Hert Stefan G. , Cromheecke Stefanie , ten Broecke Pieter W. , Mertens Els , De Blier Ivo G. , Stockman Bernard A. , Rodrigus Inez E. , Van der Linden Philippe J.
Published: November 2003

Background

The present study investigated the effects of propofol, desflurane, and sevoflurane on recovery of myocardial function in high-risk coronary surgery patients. High-risk patients were defined as those older than 70 yr with three-vessel disease and an ejection fraction less than 50% with impaired length-dependent regulation of myocardial function.

Methods

Coronary surgery patients (n = 45) were randomly assigned to receive either target-controlled infusion of propofol or inhalational anesthesia with desflurane or sevoflurane. Cardiac function was assessed perioperatively and during 24 h postoperatively using a Swan-Ganz catheter. Perioperatively, a high-fidelity pressure catheter was positioned in the left and right atrium and ventricle. Response to increased cardiac load, obtained by leg elevation, was assessed before and after cardiopulmonary bypass (CPB). Effects on contraction were evaluated by analysis of changes in dP/dt(max). Effects on relaxation were assessed by analysis of the load-dependence of myocardial relaxation. Postoperative levels of cardiac troponin I were followed for 36 h.

Results

After CPB, cardiac index and dP/dt(max) were significantly lower in patients under propofol anesthesia. Post-CPB, leg elevation resulted in a significantly greater decrease in dP/dt(max) in the propofol group, whereas the responses in the desflurane and sevoflurane groups were comparable with the responses before CPB. After CPB, load dependence of left ventricular pressure drop was significantly higher in the propofol group than in the desflurane and sevoflurane group. Troponin I levels were significantly higher in the propofol group.

Conclusions

Sevoflurane and desflurane but not propofol preserved left ventricular function after CPB in high-risk coronary surgery patients with less evidence of myocardial damage postoperatively.
Propofol and Sufentanil Titration with the Bispectral Index to Provide Anesthesia for Coronary Artery Surgery
Authors: Forestier François , Hirschi Marie , Rouget Pierre , Rigal Jean-Cristophe , Videcoq Michel , Girardet Pierre , Durand Michel , Maitrasse Bruno , Girard Claude , Lehot Jean-Jacques , Du Grés Bernard , Sellin Michel , Depoix Jean-Pol , Janvier Gérard , Longrois Dan
Published: November 2003

Background

To provide anesthesia for cardiac surgery, hypnotics and opioids are frequently titrated on variables such as mean arterial pressure and heart rate. In this study conducted in patients scheduled to undergo coronary artery bypass grafting, propofol and sufentanil, both administered by computer-controlled infusion, were titrated on the Bispectral Index (BIS) values using a predefined algorithm.

Methods

After written informed consent, 110 patients, 95 men and 15 women aged 61 (9) yr [mean (SD)], were randomly allocated to receive predicted sufentanil effect site concentrations (Ce) of 0.5, 0.75, 1, 1.25, and 1.5 ng/ml, decreased by a third after sternotomy (groups 1-5). Target induction propofol concentration was 1.5 microg/ml and subsequently adjusted on BIS values. The following parameters were recorded: BIS values, predicted propofol Ce, the number of changes of propofol target, mean arterial pressure, heart rate, the number of bolus injection and doses of vasoconstrictor and vasodilator drugs, time to tracheal extubation, postoperative awareness and satisfaction scores, and cumulative morphine doses for the first postoperative day.

Results

One patient randomized to group 1 required 0.75 ng/ml sufentanil Ce instead of 0.5 ng/ml for increased BIS values on tracheal intubation. BIS values were similar in the five groups. The predicted propofol Ce values were different (P < 0.05; analysis of variance) among the five groups: 1.59 (0.47) to 1.23 (0.25) microg/ml in group 1 and group 4, respectively. Significantly fewer changes of propofol target were required in group 4 as compared to group 1. There were no differences among the five groups for mean arterial pressure, heart rate, time to tracheal extubation, awareness, satisfaction scores, and morphine requirements.

Conclusion

These results suggest the BIS, as part of an algorithm that uses both the absolute BIS value and its increase following tracheal intubation, can be used to effectively titrate both propofol and sufentanil. A predicted sufentanil Ce of 1.25 ng/ml before and 0.8 ng/ml after sternotomy was associated with the lowest predicted propofol Ce and fewer changes of propofol target. Lower sufentanil concentrations required higher propofol concentrations and more frequent changes of the target propofol concentration and were associated with similar hemodynamic tolerance.
The Influence of Hemorrhagic Shock on Propofol
Authors: Johnson Ken B. , Egan Talmage D. , Kern Steven E. , White Julia L. , McJames Scott W. , Syroid Noah , Whiddon Derek , Church Ty
Published: November 2003

Background

Propofol is a common sedative hypnotic for the induction and maintenance of anesthesia. Clinicians typically moderate the dose of propofol or choose a different sedative hypnotic in the setting of severe intravascular volume depletion. Previous work has established that hemorrhagic shock influences both the pharmacokinetics and pharmacodynamics of propofol in the rat. To investigate this further, the authors studied the influence of hemorrhagic shock on the pharmacology of propofol in a swine isobaric hemorrhage model.

Methods

After approval from the Animal Care Committee, 16 swine were randomly assigned to control and shock groups. The shock group was bled to a mean arterial blood pressure of 50 mmHg over a 20-min period and held there by further blood removal until 30 ml/kg of blood was removed. Propofol 200 microg. kg(-1). min(-1) was infused for 10 min to both groups. Arterial samples (15 from each animal) were collected at frequent intervals until 180 min after the infusion began and analyzed to determine drug concentration. Pharmacokinetic parameters for each group were estimated using a three-compartment model. The electroencephalogram Bispectral Index Scale was used as a measure of drug effect. The pharmacodynamics were characterized using a sigmoid inhibitory maximal effect model.

Results

The raw data demonstrated higher plasma propofol levels in the shock group. The pharmacokinetic analysis revealed slower intercompartmental clearances in the shock group. Hemorrhagic shock shifted the concentration effect relationship to the left, demonstrating a 2.7-fold decrease in the effect site concentration required to achieve 50% of the maximal effect in the Bispectral Index Scale.

Conclusions

Hemorrhagic shock altered the pharmacokinetics and pharmacodynamics of propofol. Changes in intercompartmental clearances and an increase in the potency of propofol suggest that less propofol would be required to achieve a desired drug effect during hemorrhagic shock.
Age-dependent Responses to Thermal Hyperalgesia and Mechanical Allodynia in a Rat Model of Acute Postoperative Pain
Authors: Ririe Douglas G. , Vernon Teri L. , Tobin Joseph R. , Eisenach James C.
Published: November 2003

Background

Developmental differences in short- and long-term responses to pain, especially surgical pain, have received minimal attention. The purpose of the present study was to examine postoperative responses in rats of developmental ages paralleling the infant to young adult human.

Methods

The withdrawal threshold to von Frey filament testing and withdrawal latency to hind-paw radiant heating were determined before and for various times after hind-paw incision in rats 2, 4, and 16 weeks of age. Control rats of these ages were observed serially without surgery.

Results

In control animals, younger rats were more sensitive to mechanical stimulation and less sensitive to thermal stimulation. Paw incision resulted in similar changes to both types of stimulation in all age groups, peaking 4 h after surgery. However, the return to normal sensitivity to mechanical stimulation, as measured by return of threshold to 80% of normal, occurred more quickly in 2-week-old than in 4- and 16-week-old animals. In contrast, there was no age difference for time to return to normal sensitivity to thermal stimulation after surgery.

Conclusions

The more rapid recovery of the younger animals from the mechanical allodynia but not thermal hypersensitivity after surgery suggests the presence of developmental differences in modulation of A-fiber sensitization after surgery. However, the lack of age difference in recovery of thermal hypersensitivity after surgery suggests that sensitization of C-fiber input has a similar time course of resolution of pain over the ages studied in this model. The neural bases for these developmental differences are under study and may lead to a better understanding of pain during development and altered approaches to treatment of postoperative pain in neonates and infants.
Acute Isovolemic Anemia Does Not Impair Peripheral or Central Nerve Conduction
Authors: Weiskopf Richard B. , Aminoff Michael J. , Hopf Harriet W. , Feiner John , Viele Maurene K. , Watson Jessica J. , Ho Rachel , Songster Christopher , Toy Pearl
Published: November 2003

Background

Previous studies have found subtle slowing of responses in tests of addition and digit-symbol substitution during acute severe isovolemic anemia to a hemoglobin concentration of 5 g/dl in healthy unmedicated humans. In this study, the authors tested the hypothesis that such changes relate to the slowing of afferent neural traffic.

Methods

The median nerve was stimulated at the wrist in seven healthy unmedicated volunteers before and after induction of acute isovolemic anemia to a nadir hemoglobin concentration of 5.1 +/- 0.3 g/dl (mean +/- SD). Times for neural impulses to travel from the stimulus site to the brachial plexus, cervical spinal cord, and cerebral cortex were measured using somatosensory evoked potentials. Tests were repeated during acute anemia with the subject breathing oxygen. As a control for time and intrasubject variation, the testing was repeated on a separate day when anemia was not produced at times equivalent to those on the experimental day.

Results

Induced acute severe isovolemic anemia decreased nerve conduction latencies from the wrist to the contralateral cerebral cortex (i.e., to the N20 peak) by 2.3 +/- 1.6% compared with values at a mean hemoglobin concentration of 12.7 g/dl (P < 0.01). These decreased latencies were due solely to an increased peripheral conduction velocity, from the wrist to the brachial plexus (P < 0.05), and were not altered when subjects breathed oxygen (P > 0.05). Conduction velocity from the brachial plexus or cervical spinal cord to the cerebral cortex did not change with acute anemia (P > 0.05). Latencies did not differ on the control day among the times of testing (all P > 0.05), nor did they differ at baseline between the control and experimental days (all P > 0.05).

Conclusion

Somatosensory evoked potential latencies were not increased by acute severe isovolemic anemia, making it unlikely that the afferent portion of the neural system is responsible for slowing of cognitive responses previously observed during acute anemia. Because severe isovolemic anemia did not increase somatosensory evoked potential latencies, etiologies other than anemia should be sought if latencies are increased during intraoperative monitoring.
Pharmacokinetics of Propofol Administered by Target-controlled Infusion to Alcoholic Patients
Authors: Servin Frédérique S. , Bougeois Bernard , Gomeni Roberto , Mentré France , Farinotti Robert , Desmonts Jean-Marie
Published: November 2003

Background

Chronic alcoholic patients are frequently presented for anesthesia and surgery. These patients require higher doses of propofol than control patients for induction of anesthesia, but whether this is because of changes in pharmacokinetics or pharmacodynamics is not known. This study was designed to investigate the influence of chronic ethanol intake on propofol pharmacokinetics.

Methods

Fifteen chronic alcoholic and 15 control patients, receiving propofol by target-controlled infusion for otolaryngologic surgery, were studied. Blood propofol concentrations were measured at regular intervals during and after the propofol infusion. Nonlinear mixed-effects population models (NONMEM) examining the influence of alcoholism were constructed. The influence of recovery on propofol pharmacokinetic parameters was also addressed.

Results

The total amount of propofol and the predicted and measured concentrations during all phases of anesthesia did not differ between the two groups. The fact that the measured concentrations at the time of opening eyes were similar further confirmed that the potency of propofol was not modified by the alcoholic status of the patients. Chronic alcoholism was associated with only mild changes in propofol pharmacokinetics (increase in rapid intercompartmental clearance and greater interindividual variability in the central volume of distribution). The rebound in concentration frequently observed during the recovery phase could be related to decreased propofol peripheral volumes of distribution despite an increase in elimination clearance.

Conclusions

Chronic alcoholism induces only mild changes in the pharmacokinetics of propofol. Conversely, propofol pharmacokinetics are markedly different during anesthesia and surgery or after opening eyes in the recovery period.
Model Predictions of Gas Embolism Growth and Reabsorption during Xenon Anesthesia
Authors: Maria Naomi Sta , Eckmann David M.
Published: November 2003

Background

It is not readily obvious whether an intravascular bubble will grow or shrink in a particular tissue bed. This depends on the constituent gases initially present in the bubble, the surrounding tissue, and the delivered gas admixture. The authors used a computational model based on the physics of gas exchange to predict cerebrovascular embolism behavior during xenon anesthesia.

Methods

The authors estimated values of gas transport parameters missing from the literature. The computational model was used with those parameters to predict bubble size over time for a range of temperatures (18 degrees -39 degrees C) used during extracorporeal circulation.

Results

Bubble size over time is highly nonlinearly dependent on multiple factors, including diffusivity, solubility, gas partial pressures, magnitude of concentration gradients, vessel diameter, and temperature. Xenon- and oxygen-containing bubbles continue to grow during xenon delivery. Bubble volume doubles from 50 to 100 nl in approximately 3-68 min, depending on initial gas composition and bubble shape. Bubble growth and reabsorption are relatively insensitive to temperature in the physiologic and surgical range.

Conclusions

Xenon anesthesia results in gas exchange conditions that favor bubble growth, which may worsen neurologic injury from gas embolism. The concentration gradients can be manipulated by discontinuation of xenon delivery to promote reabsorption of xenon-containing bubbles. Estimated growth and reabsorption rates at normothermia can be applied to temperature extremes of cardiopulmonary bypass.
The Actions of Sevoflurane and Desflurane on the γ-Aminobutyric Acid Receptor Type A
Authors: Nishikawa Koichi , Harrison Neil L.
Published: November 2003

Background

Previous studies have shown that specific amino acid residues in the putative second transmembrane segment (TM2) of the gamma-aminobutyric acid receptor type A (GABAA) receptor play a critical role in the enhancement of GABAA receptor function by halothane, enflurane, and isoflurane. However, very little is known about the actions of sevoflurane and desflurane on recombinant GABAA receptors. The aim of this study was to examine the effects of sevoflurane and desflurane on potentiation of GABA-induced responses in the wild-type GABAA receptor and in receptors mutated in TM2 of the alpha1, alpha 2, or beta 2 subunits.

Methods

GABAA receptor alpha 1 or alpha 2, beta 2 or beta 3, and gamma 2s subunit cDNAs were expressed for pharmacologic study by transfection of human embryonic kidney 293 cells and assayed using the whole cell voltage clamp technique. Concentration-response curves and EC50 values for agonist were determined in the wild-type alpha 1 beta 2 gamma 2s and alpha 2 beta 3 gamma 2s receptors, and in receptors harboring mutations in TM2, such as alpha1(S270W)beta 2 gamma 2s, alpha 1 beta 2(N265W)gamma 2s, and alpha2(S270I)beta 3 gamma 2s. The actions of clinically relevant concentration of volatile anesthetics (isoflurane, sevoflurane, and desflurane) on GABA activated Cl- currents were compared in the wild-type and mutant GABAA receptors.

Results

Both sevoflurane and desflurane potentiated submaximal GABA currents in the wild-type GABAA alpha 1 beta 2 gamma 2s receptor and alpha 2 beta 3 gamma 2s receptor. Substitution of Ser270 in TM2 of the alpha subunit by a larger amino acid, tryptophan (W) or isoleucine (I), as in alpha1(S270W)beta 2 gamma 2s and alpha 2(S270I)beta 3 gamma 2s, completely abolished the potentiation of GABA-induced currents by these anesthetic agents. In contrast, mutation of Asn265 in TM2 of the beta subunit to tryptophan (W) did not prevent potentiation of GABA-induced responses. The actions of sevoflurane and desflurane in the wild-type receptor and in mutated receptors were qualitatively and quantitatively similar to those observed for isoflurane.

Conclusions

Positions Ser270 of the GABAA alpha1 and alpha2 subunits, but not Asn265 in the TM2 of the beta2 subunit, are critical for regulation of the GABAA receptor by sevoflurane and desflurane, as well as isoflurane, consistent with the idea that these three volatile anesthetics share a common site of actions on the alpha subunit of the GABAA receptor.
Ability of the Bispectral Index, Autoregressive Modelling with Exogenous Input-derived Auditory Evoked Potentials, and Predicted Propofol Concentrations to Measure Patient Responsiveness during Anesthesia with Propofol and Remifentanil
Authors: Struys Michel M. R. F. , Vereecke Hugo , Moerman Annelies , Jensen Erik Weber , Verhaeghen David , De Neve Nicolaas , Dumortier Frank J. E. , Mortier Eric P.
Published: November 2003

Background

This study was conducted to compare the performance accuracy of the independent variables Bispectral Index (BIS), A-Line ARX index (AAI), and predicted propofol effect-site concentration (CePROP) to measure the dependent variables of loss of responses to different stimulation defined as loss of response to verbal command (LORverbal), eyelash reflex (LORlash), and noxious stimulus (LORnoxious) during stepwise increased levels of propofol infusion with and without remifentanil.

Methods

Forty-five patients were randomly allocated to one of three groups (0, 2, and 4 ng/ml remifentanil) to receive graded CePROP and predicted effect compartment controlled remifentanil (CeREMI). At every step, the ability to respond to verbal command using the Observer's Assessment of Alertness/Sedation Scale (OAA/S), eyelash reflex, and electrical tetanic noxious stimulus were compared against BIS, AAI, and CePROP. Prediction probability and sensitivity/specificity were calculated.

Results

Increasing CeREMI increased BIS and AAI values at LORverbal and LORlash and decreased CePROP. Similar findings were found for LORnoxious. The overall prediction probability to measure the hypnotic component of anesthesia remained accurate in the three groups for BIS, AAI, and CePROP. Combined information from CePROP, CeREMI, and BIS or AAI increased the overall prediction probability for predicting the OAA/S scale and LORlash. Less accuracy to LORnoxious was found in all independent variables.

Conclusions

Although BIS, AAI, and CePROP were influenced by remifentanil during propofol administration, their ability to detect OAA/S and LORlash remained accurate. Improved performance is obtained when BIS and AAI are measured in conjunction with drug targeted effect-site concentrations. Remifentanil decreases the ability of these independent variables to detect LORnoxious.
Comparison of Intracarotid and Intravenous Propofol for Electrocerebral Silence in Rabbits
Authors: Wang Mei , Joshi Shailendra , Emerson Ronald G.
Published: November 2003

Background

The high lipid solubility that permits rapid transfer across the blood-brain barrier makes propofol attractive for intracarotid injection. The authors hypothesized that intracarotid injection produces electrocerebral silence at a fraction of the intravenous dose and with less adverse systemic and cerebrovascular side effects.

Methods

The authors compared the systemic and cerebrovascular effects of intracarotid and intravenous propofol during transient (10 s) and sustained (1 h) electrocerebral silence in anesthetized New Zealand White rabbits. Hemispheric electrocerebral activity, mean arterial blood pressure, ipsilateral and contralateral cerebral blood flow, tympanic temperature, and end-tidal carbon dioxide were continuously monitored in these animals. Changes in outcome variables were analyzed at four time points: at baseline, during electrical silence, during burst suppression, and after recovery of electrocerebral activity. Propofol (1%) was injected as intracarotid (0.1 ml) or intravenous (0.5 ml) boluses.

Results

Intracarotid propofol produced electrocerebral silence at one fifth (sustained silence) to one tenth (transient silence) of the intravenous dose. Compared with baseline values, the mean arterial pressure and ipsilateral cerebral blood flow remained unchanged or decreased transiently during electrocerebral silence with intracarotid propofol. In contrast, intravenous propofol resulted in systemic hypotension and a decrease in ipsilateral cerebral blood flow.

Conclusions

Intracarotid propofol resulted in electrocerebral silence at a fraction of the intravenous dose that was not associated with systemic hypotension or a sustained decrease in the cerebral blood flow. Intracarotid propofol could be potentially useful for providing electrocerebral silence when cerebral perfusion is at risk.
Use of a Continuous Local Anesthetic Infusion for Pain Management after Median Sternotomy
Authors: White Paul F. , Rawal Shivani , Latham Paige , Markowitz Scott , Issioui Tijani , Chi Lei , Dellaria Suzanne , Shi Chen , Morse Lisa , Ing Caleb
Published: November 2003

Background

The use of large doses of opioid analgesics to treat pain after cardiac surgery can prolong the time to tracheal extubation and interfere with recovery of bowel and bladder function in the postoperative period. Therefore, the authors investigated the efficacy of a continuous infusion of bupivacaine 0.25% or 0.5%, at the median sternotomy site, for 48 h after cardiac surgery in reducing the opioid analgesic requirement and improving the recovery process.

Methods

In this prospective, randomized, placebo-controlled, double-blind clinical trial, 36 consenting patients undergoing open-heart surgery with a standardized general anesthetic technique had two indwelling infusion catheters placed at the median sternotomy incision site at the end of surgery. The patients were randomly assigned to receive normal saline (control), bupivacaine 0.25% or bupivacaine 0.5% via an elastomeric infusion pump at a constant rate of 4 ml/h for 48 h. Patients evaluated their chest pain using an 11-point verbal rating scale, with 0 = no pain to 10 = worst pain imaginable. In addition, the postoperative opioid analgesic requirements and opioid-related adverse effects were recorded. Patient satisfaction with their pain management was assessed at specific intervals during the postoperative period using a 100-point verbal rating scale, with 1 = highly dissatisfied to 100 = highly satisfied. Finally, serum bupivacaine concentrations were measured 24 and 48 h after surgery.

Results

Compared with the control group, there was a statistically significant reduction in verbal rating scale pain scores and patient-controlled analgesia morphine use in the bupivacaine-0.5% group. Patient satisfaction with their pain management was also improved in the bupivacaine-0.5% (vs. control) group. However, there were no significant differences in patient-controlled analgesia morphine use between the bupivacaine-0.25% and control groups. Although the duration of the intensive care unit stay (30 vs. 34 h, respectively) was not significantly decreased, the time to ambulation (1 +/- 0.5 vs. 2 +/- 1 days, respectively) and the duration of hospital stay (4.2 vs. 5.7 days, respectively) were lower in the bupivacaine-0.5% group than in the control group. Mean +/- SD serum bupivacaine concentrations at 48 h in the bupivacaine-0.25% and bupivacaine-0.5% groups were 0.5 +/- 0.5 and 1.3 +/- 0.7 microg/ml, respectively.

Conclusion

A continuous infusion of bupivacaine 0.5% at 4 ml/h is effective for decreasing pain and the need for opioid analgesic medication as well as for improving patient satisfaction with their pain management after cardiac surgery. Patients in the bupivacaine-0.5% group were able to ambulate earlier, leading to a reduced length of hospital stay.