bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemodynamic Responses to Intravascular Injection of Epinephrine-containing Epidural Test Doses in Adults during General Anesthesia
Authors: Liu Spencer S. , Carpenter Randall L.
Published: November 2003

Background

Epidural anesthesia is sometimes initiated during general anesthesia, yet few data exist concerning efficacy of epinephrine-containing test doses.

Methods

Thirty-six patients were randomized to receive either 0.5 MAC isoflurane, 1 MAC isoflurane, or 0.5 MAC each (1 MAC total) of isoflurane and nitrous oxide. Each subject received intravenous saline followed by three test doses containing 45 mg lidocaine with 7.5, 15, and 30 micrograms epinephrine in a randomized, double-blind fashion. Heart rate and systolic, diastolic, and mean blood pressures were measured for 5 min after injection. Positive hemodynamic criteria identifying intravascular injection were determined from peak increases in hemodynamics during administration of saline. Dose-effect relationships between epinephrine and peak increases in hemodynamics were assessed with linear regression. Minimum required doses of epinephrine to produce peak positive hemodynamic increases on average were determined from linear regression.

Results

Positive hemodynamic criteria were identified as increases in heart rate > or = 8 beats/min, systolic blood pressure > or = 13 mmHg, diastolic blood pressure > or = 7 mmHg, and mean blood pressure > or = 9 mmHg. Significant dose-effect relationships were observed for epinephrine and peak increases in hemodynamics (correlation coefficients ranged from 0.61-0.91). Minimum required doses of epinephrine ranged from 6 to 19 micrograms depending on hemodynamic measurement and anesthetic group.

Conclusions

Hemodynamic responses to intravascular injection of test doses vary with dose of epinephrine and depth and type of general anesthetic used. Thus, the 15 micrograms epinephrine contained in the standard test dose may not be sufficient during all anesthetic conditions.
Cytomegalovirus
Authors: Papazian Laurent , Fraisse Alain , Garbe Louise , Zandotti Christine , Thomas Pascal , Saux Pierre , Perrin Gilles , Gouin Francois
Published: November 2003

Background

Cytomegalovirus (CMV) frequently is observed in immunocompromised hosts. The aim of this study was to report cases of ventilator-associated CMV pneumonia diagnosed by pathologic examination in intensive care patients without acquired immunodeficiency syndrome or hematologic malignancy or who were not receiving immunosuppressive agents.

Methods

From June 1, 1989, to May 31, 1994, 2,785 patients were hospitalized. During the study period, 60 autopsies and 26 open-lung biopsies were performed in nonimmunocompromised patients who were seen with acute respiratory failure and/or symptoms suggestive of ventilator-associated pneumonia. Cytomegalovirus pneumonia was diagnosed using pulmonary samples by the identification of large cells with large nuclei containing a basophilic or eosinophilic inclusion surrounded by a light halo. These typical findings always were associated with a diffuse interstitial pneumonitis.

Results

Cytomegalovirus pneumonia was diagnosed after histologic examination in 25 patients. The reason for admission to the intensive care unit was major surgery in 13 patients and medical problems in 12 patients. Ventilator-associated CMV pneumonia was diagnosed by histologic examination 22.4 +/- 8.8 days after admission to the intensive care unit (median 18 days; range 10-40 days). The clinical description was similar with the 25 patients who were seen with ventilator associated CMV pneumonia and the 61 patients without ventilator-associated CMV pneumonia. However, there was a more severe hypoxemia 72 +/- 16 vs. 95 +/- 41 mmHg, P < 0.05) and a higher Weinberg's radiologic score (9.2 +/- 1.9 vs. 7.4. +/- 2.7, P < 0.05) in the ventilator-associated CMV pneumonia group. Diagnosis of ventilator-associated CMV pneumonia was made for 9 of 17 patients when shell-vial culture technique using fluorescein-labelled antibody E 13 was performed on bronchoalveolar lavage products. Four of the eight patients treated by ganciclovir therapy died of multiple organ dysfunction syndrome.

Conclusions

The diagnosis of ventilator-associated CMV pneumonia should not be excluded in intensive care patients, even those without acquired immunodeficiency syndrome, hematologic malignancy, or immunosuppressive agents on admission.
Pharmacodynamic Interaction between Propofol and Alfentanil When Given for Induction of Anesthesia
Authors: Vuyk Jaap , Engbers Frank H. M. , Burm Anton G. L. , Vletter Arie A. , Griever Gerard E. R. , Olofsen Erik , Bovill James G.
Published: November 2003

Background

Propofol and alfentanil often are combined during induction of anesthesia. However, the interaction between these agents during induction has not been studied in detail. The influence of alfentanil on the propofol concentration-effect relationships was studied for loss of eyelash reflex, loss of consciousness, and hemodynamic function in 20 unpremedicated ASA physical status 1 patients aged 20-55 yr.

Methods

Patients were randomly divided into four groups to receive a computer- controlled infusion of alfentanil with target concentrations of 0, 50, 200, or 400 ng/ml (groups A, B, C, and D, respectively). While the target concentration of alfentanil was maintained constant, patients received a computer- controlled infusion of propofol, with an initial target concentration of 0.5-1 microgram/ml, that was increased every 12 min by 0.5-1 microgram/ml. Every 3 min, the eyelash reflex and state of consciousness were tested an an arterial blood sample was taken for blood propofol and plasma alfentanil determination. The propofol-alfentanil concentration-response relationships for loss of eyelash reflex and loss of consciousness were determined by nonlinear regression, and for the percentage of change in systolic blood pressure and heart rate by logistic regression.

Results

The patient characteristics did not differ significantly among the four groups. The patients in groups A and B continued to breathe adequately, whereas all patients in groups C and D required assisted ventilation. End-tidal carbon dioxide partial pressure remained less than 46 mmHg in all patients. With plasma alfentanil concentrations increasing from 0 to 500 ng/ml, the EC(50) of propofol decreased from 2.07 to 0.83 microgram/ml for loss of eyelash reflex and from 3.62 to 1.55 microgram/ml for loss of consciousness. With plasma alfentanil concentrations increasing from 0 to 500 ng/ml, the blood propofol concentrations associated with a 10% decrease in systolic blood pressure and heart rate decreased from 1.68 to 0.17 microgram/ml and from 2.36 to 0.04 microgram/ml, respectively.

Conclusions

Alfentanil significantly reduces blood propofol concentrations required for loss of eyelash reflex and loss of consciousness. In addition, alfentanil enhances the depressant effects of propofol on systolic blood pressure and heart rate. Hemodynamic stability, therefore, does not increase in patients receiving propofol in combination with alfentanil compared to those receiving propofol as the sole agent for induction of anesthesia.
Mechanical Significance of Respiratory Muscle Activity in Humans during Halothane Anesthesia
Authors: Warner David O. , Warner Mark A. , Ritman Erik L.
Published: November 2003

Background

Prior human studies have shown that halothane attenuates activity in the parasternal intercostal muscle and enhances phasic activity in respiratory muscles with expiratory actions. This expiratory muscle activity could contribute to reductions in the functional residual capacity produced by anesthesia. Termination of this activity could contribute to the maintenance of inspiratory rib cage expansion. The purpose of this study was to estimate in humans the mechanical significance of expiratory muscle activity during halothane anesthesia and to search for the presence of scalene muscle activity during halothane anesthesia that might contribute to inspiratory rib cage expansion.

Methods

Six subjects (3 males, 3 females) were studied while awake and during 1.2 MAC halothane anesthesia, both during quiet breathing and during carbon dioxide rebreathing. Respiratory muscle activity was measured using fine-wire electromyography electrodes. Chest wall configuration was determined using images of the thorax obtained by three-dimensional, fast computed tomography and respiratory impedance plethysmography. Functional residual capacity was measured by a nitrogen dilution technique. Measurements were obtained after paralysis with 0.1 mg/kg vecuronium and mechanical ventilation.

Results

Phasic inspiratory activity was present in the scalene muscle of four anesthetized subjects during quiet breathing and all anesthetized subjects during rebreathing. Phasic inspiratory activity was present in the parasternal intercostal muscle during halothane anesthesia in only the three female subjects and was enhanced by rebreathing; parasternal intercostal muscle activity was never present in anesthetized males. During anesthesia with quiet breathing, phasic expiratory activity was observed in the transversus abdominis muscles of only the three male subjects. Despite these differences in the pattern of respiratory muscle use, the pattern of chest wall responses to rebreathing was similar between males and females. When expiratory muscle activity was present, paralysis increased the end-expiratory thoracic volume by expanding the rib cage, demonstrating that this activity reduced thoracic volume in these subjects. Changes in thoracic blood volume were significant determinants of the change in functional residual capacity produced by paralysis.

Conclusions

In humans anesthetized with 1.2 MAC end-tidal halothane, there are marked interindividual differences in respiratory muscle use during quiet breathing that may be related to sex; phasic inspiratory scalene muscle and parasternal intercostal muscle activity may contribute to inspiratory rib cage expansion in some subjects; and when present, expiratory muscle activity significantly constricts the rib cage and contributes to reductions in functional residual capacity caused by halothane anesthesia.
Theoretical Assessment of Normobaric Oxygen Therapy to Treat Pneumocephalus
Authors: Dexter Franklin , Reasoner Daniel K.
Published: November 2003

Background

Pneumocephalus has been linked to several clinical conditions, including headache, lethargy, and even brain herniation or death. The effects of different normobaric oxygen concentrations and durations of therapy on the rate of air absorption were examined.

Methods

An existing mathematical model of inert gas absorption was used. The model accounts for the major phenomena that determine absorption of bubbles, including surface tension, pressure dependence of bubble size, and removal of gases to the surrounding tissue. Sensitivity analysis tested reliability of our results.

Results

Times for a 50-ml air collection to have been absorbed were 5.8, 1.9, and 0.6 weeks at an FIO2 of 0.21, 0.4, and 1.0 respectively. Thirty percent and 72% of the air was absorbed in 2 days at an FIO2 of 0.4 and 1.0, respectively. The percent decrease in time for absorption achieved by increasing the FIO2 from 0.21 was nearly identical for different volumes of air. The benefit of increasing the FIO2 decreased with progressive increases in the FIO2. Increasing the FIO2 from 0.21 to 0.4 caused the time to total air absorption to decrease by 67%. In contrast, increasing the FIO2 from 0.8 to 1.0 caused the time to total air absorption to decrease by an additional 3%.

Conclusions

Based on mathematical model predictions, an FIO2 of 0.4 or 1.0 for at least 1 week or 2 days, respectively, will significantly decrease the time for absorption of a pneumocephalus.
Semilinear Canonical Correlation Applied to the Measurement of the Electroencephalographic Effects of Midazolam and Flumazenil Reversal
Authors: Schnider Thomas W. , Minto Charles F. , Fiset Pierre , Gregg Keith M. , Shafer Steven L.
Published: November 2003

Background

The electroencephalographic (EEG) effect of benzodiazepines, and midazolam in particular, has been described using simple measures such as total power in the beta band, waves.s(-1) in the beta band and total power from aperiodic analysis. All these parameters failed to consistently describe the EEG effect of midazolam in a study in which large doses of midazolam were infused, and the effect subsequently reversed with flumazenil. Using a technique called semilinear correlation it is possible to extract a parameter from the EEG that is statistically optimally correlated with the apparent concentration of the benzodiazepine in the effect site. This method has been used to develop new univariate measures of the effects of opioids on the EEG but has not previously been applied to the EEG effects of benzodiazepines.

Methods

Data from ten subjects who received an infusion of midazolam were analyzed. The data were divided into "learning" and "test" sets. The learning set consisted of ten studies in which the volunteers received an infusion of 2.5 mg.min(-1) midazolam. Semilinear canonical correlation was used to extract an univariate descriptor of the EEG effect by weighting the different frequency bands of the EEG power spectrum. The test set comprised the same subjects on subsequent visits, in which the subjects received a continuous infusion of midazolam to maintain 20% or 80% of the peak drug effect for 3h. Twenty minutes after start of the midazolam infusion, the patient received an infusion of flumazenil to acutely reverse the benzodiazepine drug effect. The weights obtained from the learning set were tested prospectively in the test set, based on the coefficient of multiple determination, R(2), obtained by fitting the EEG effect to a sigmoid Emax model.

Results

The canonical univariate parameter of benzodiazepine drug effect on the EEG, when applied to the test set receiving the midazolam infusion with flumazenil reversal, yielded a median R(2) of 0.78. The median R(2) of six commonly used empirical EEG measures of drug effect ranged from 0.18 to 0.55.

Conclusions

The canonical univariate parameter for benzodiazepine drug effect on the EEG correlates more accurately and consistently with the predicted EEG effects of midazolam and its reversal than previously reported EEG measures of benzodiazepine effect.
Pharmacodynamics and Pharmacokinetics of Cisatracurium in Geriatric Surgical Patients
Authors: Ornstein Eugene , Lien Cynthia A , Matteo Richard S. , Ostapkovich Noeleen D. , Diaz Jaime , Wolf Karen B.
Published: November 2003

Background

Cisatracurium, one of ten stereoisomers that comprise atracurium, is more potent than atracurium and has less propensity to release histamine. This study compares the pharmacokinetics and pharmacodynamics of cisatracurium in elderly and young patients.

Methods

Twelve elderly (aged 65-82 yr) and 12 younger patients (aged 30-49 yr) were anesthetized with nitrous oxide, fentanyl, and isoflurane (0.7%, end-tidal). The mechanomyographic response to train-of-four stimulation was assessed every 15 s after the administration of cisatracurium (0.1 mg/kg). Arterial samples were obtained over 6 h. Plasma cisatracurium concentration versus time data were fit to compartmental models. Pharmacokinetic parameters were determined assuming that elimination occurred from the central compartment only. This provides accurate clearance and half-life estimates but underestimates V(ss) (reported herein as V(ss). The pharmacodynamic response was described by the neuromuscular blocking profile.

Results

Onset to 90% paralysis (mean +/- SD) was delayed in the elderly (3.4 +/- 1.0 vs. 2.5 +/- 0.6 min). Recovery profiles were the same for both groups. Elimination half-life was minimally prolonged in the elderly (25.5 +/- 3.7 vs. 21.5 +/- 2.4 min). The Vss was larger in the elderly (126 +/- 16 vs. 108 +/- 13 ml/kg), although the clearances were the same for the two groups (5.0 +/- 0.9 vs. 4.6 +/- 0.8 ml.kg(-1).min(-1).

Conclusions

There are minor differences in the pharmacokinetics of cisatracurium between elderly and young patients. These differences are not associated with changes in recovery profile after a single bolus dose, although the mean time to onset was approximately 1 min longer in elderly patients.
Propofol Inhibits Cardiac L-Type Calcium Current in Guinea Pig Ventricular Myocytes
Authors: Yang Ching-Yue , Wong Chih-Shung , Yu Chuan-Cheng , Luk Hsiang-Ning , Lin Cheng-I
Published: November 2003

Background

Propofol may exert negative inotropic and chronotropic actions in the heart. Single-channel studies show that propofol affects the kinetics of opening and closing of cardiac L-type calcium channels (ICa(L)) without altering channel conductance. The aim of this study was to investigate the mechanisms of depressant effects of propofol on cardiac whole-cell ICa(L).

Methods

Single ventricular myocytes were freshly dissciated from guinea pig hearts using enzymatic isolation. One-suction electrode voltage-clamp technique (whole-cell mode) was used. LCa(L) was separated from other contaminated ionic currents. Propofol was applied in the commercial 10% Intralipid emulsion formula (Zeneca, UK).

Results

In isolated cardiomyocytes, propofol significantly inhibited whole-cell ICa(L) in a concentration-dependent manner (K D = 52.0 microM; Hill coefficient = 1.3). The solvent (Intralipid) did not affect ICa(L). Propofol decreased ICa(L) at all potentials tested along the voltage axis and reduced the slope conductance. The threshold potential for activation and the peak potential of the current-voltage relationship were not changed by propofol. The steady-state activation curves overlapped in the absence and the presence of 56 microM propofol. In contrast, the steady-state inactivation curve was shifted in the hyperpolarizing direction. The time course of the recovery from inactivation was delayed by 56 microM propofol. The blocking action on ICa(L) of propofol shows marked resting block and use-dependent block. Propofol caused more pronounced inhibition at a higher stimulation frequency. The effect of propofol on the inactivation process was even more clear on ICa(L).

Conclusions

The authors conclude tha propofol, at supratherapeutic concentrations, inhibits cardiac ICa(L). This inhibition is mainly due to a shift of inactivation curve and a reduction in slope conductance.
Ventilation with Constant Versus Decelerating Inspiratory Flow in Experimentally Induced Acute Respiratory Failure
Authors: Markstrom Agneta M. , Lichtwarck-Aschoff Michael , Svensson Bjorn A. , Nordgren K. Anders , Sjostrand Ulf H.
Published: November 2003

Background

Recognition of the potential for ventilator-associated lung injury has renewed the debate on the importance of the inspiratory flow pattern. The aim of this study was to determine whether a ventilatory pattern with decelerating inspiratory flow, with the major part of the tidal volume delivered early, would increase functional residual capacity at unchanged (or even reduced) inspiratory airway pressures and improve gas exchange at different positive end-expiratory pressure levels.

Methods

Surfactant depletion was induced by repeated bronchoalveolar lavage in 13 anesthetized piglets. Decelerating and constant inspiratory flow ventilation was applied at positive end-expiratory pressure levels of 22, 17, 13, 9, and 4 cm H(2)O. Tidal volume, inspiration-to-expiration ratio, and ventilatory frequency were kept constant. Airway pressures, gas exchange, functional residual capacity (using a wash-in/washout method with sulfurhexafluoride), central hemodynamics, and extravascular lung water (using the thermo-dye-indicator dilution technique) were measured.

Results

Decelerating inspiratory flow yielded a lower arterial carbon dioxide tension compared to constant flow, that is, it improved alveolar ventilation. There were no differences between the flow patterns regarding end-inspiratory occlusion airway pressure, end-inspiratory lung volume, static compliance, or arterial oxygen tension. No differences were seen in hemodynamics and oxygen delivery.

Conclusions

The decelerating inspiratory flow pattern increased carbon dioxide elimination, without any reduction of inspiratory airway pressure or apparent improvement in arterial oxygen tension. It remains to be established whether these differences are sufficiently pronounced to justify therapeutic consideration.
Pseudocholinesterase-mediated Hydrolysis Is Superior to Neostigmine for Reversal of Mivacurium-induced Paralysis In Vitro
Authors: Yang H. S. , Goudsouzian N. , Martyn J. A. J.
Published: November 2003

Background

The metabolic hydrolysis of mivacurium (and succinylcholine) is markedly impaired in the presence of hereditary or acquired defects of pseudocholinesterase. Clinical reports are conflicting as to the utility of anticholinesterases, in the reversal of mivacurium paralysis. In the current study, the role of exogenous cholinesterases and/or of anticholinesterase, neostigmine, in the reversal of deep mivacurium-induced paralysis, was studied. The rat phrenic-diaphragm preparation, in a fixed volume of Krebs solution, was chosen to eliminate the confounding effects on the dissipation of neuromuscular effects caused by hydrolysis, elimination, and redistribution of the drug.

Methods

In the phrenic-diaphragm preparation, mivacurium was administered to obtain >90% single twitch inhibition. Single twitch responses (0.1 Hz) were monitored for 60 min, after which the response to train-of-four stimulation was tested. The reversal of mivacurium by 0.5, 1.0, or 2.0 units/ml of (true) acetylcholinesterase, bovine pseudocholinesterase, or human plasma cholinesterase and by neostigmine, 0.1, 1.0, or 10.0 micrograms/ml tested. The efficacy of human plasma cholinesterase, 1 unit/ml in combination with each of the above neostigmine concentrations, also was examined. The reversal of succinylcholine-induced paralysis by the acetylcholinesterase, bovine pseudocholinesterase, or human plasma cholinesterase (1 unit/ml) alone and in the presence of neostigmine (10.0 micrograms/ml) was additionally tested as a positive control. A train-of-four ratio > 0.75 was considered adequate reversal.

Results

Acetylcholinesterase was a poor hydrolyzer of mivacurium, as bioassayed by reversal of paralysis. Bovine pseudocholinesterase in concentrations of 0.5 and 1.0 units/ml did not effectively reverse single twitch and train-of-four responses by 60 min, but bovine pseudocholinesterase (2 units/ml) and all concentrations of human plasma cholinesterase did. Neostigmine alone, tested at all concentrations, was an incomplete reversal drug. Clinical or therapeutic concentrations (0.1 and 1.0 micrograms/ml) of neostigmine did not, but pharmacologic concentrations (10 micrograms/ml) interfere with the efficacy of human plasma cholinesterase (1 unit/ml). Bovine pseudocholinesterase and human plasma cholinesterase equally reversed the effects of succinylcholine but acetylcholinesterase did not, whereas the addition of 10 micrograms/ml neostigmine to the enzymes inhibited the reversal of succinylcholine.

Conclusions

Human plasma cholinesterase will reverse mivacurium more effectively than bovine pseudocholinesterase, but both will effectively reverse succinylcholine. Acetylcholinesterase has no effects on either relaxant. The anticholinesterase neostigmine was an incomplete reversal drug. Pharmacologic concentrations of anticholinesterases do, while clinical or therapeutic concentrations do not, completely inhibit the metabolic activity of pseudocholinesterases.
Enzymatic Versus Pharmacologic Antagonism of Profound Mivacurium-induced Neuromuscular Blockade
Authors: Naguib Mohamed , Selim Mahdi , Bakhamees Hassan S. , Samarkandi Abdulhamid H. , Turkistani Ahmed
Published: November 2003

Background

Mivacurium, a nondepolarizing muscle relaxant, is hydrolyzed by butyrylcholinesterase. The use of butyrylcholinesterase for antagonism of profound mivacurium-induced blockade has not been studied in humans. In part 1 of this two-part study, the authors examined the relationship between the posttetanic count (PTC) and recovery from profound mivacurium-induced blockade. In part 2, an attempt was made to antagonize a quantified level of profound mivacurium-induced blockade using either butyrylcholinesterase, edrophonium, or neostigmine.

Methods

Eighty-seven ASA physical status 1 or 2 adult patients were given 0.15 mg.kg-1 mivacurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. They were randomly assigned to eight groups. Neuromuscular function was monitored by recording the mechanomyographic response of the adductor pollicis to PTC and train-of-four (TOF) stimulation in all patients except those in group 1 where the TOF was the only pattern used. In part 1, neuromuscular function was allowed to recover spontaneously in ten patients (group 1; control-TOF) until TOF ratio (the amplitude of the fourth evoked response as a fraction of the first evoked response T4/T1) had reached 0.75. The temporal relationship between PTC and the first reaction to TOF stimulation was determined in another 31 patients, and neuromuscular function in 10 of these patients was allowed to recover spontaneously until TOF ratio had reached 0.75. The temporal relationship between PTC and the first reaction to TOF stimulation was determined in another 21 patients, and neuromuscular function in 10 of these patients was allowed to recover spontaneously, until TOF ratio had reached 0.75 (group 2; control-PTC). In part 2, the antagonism of mivacurium-induced profound (PTC > or = 1; groups 3-6) and 90% block (groups 7-8) of twitch height were investigated in another 56 patients. Groups 3 and 7 received neostigmine 0.06 mg.kg-1 whereas groups 4 and 8 received edrophonium 1 mg.kg-1, respectively. Groups 5 and 6 received exogenous human butyrylcholinesterase equivalent to activity present in 25 or 70 ml.kg-1 of human plasma, respectively.

Results

Neither butyrylcholinesterase nor edrophonium shortened the times from first PTC response to TOF = 0.75 compared to group 2. Neostigmine resulted in prolongation of recovery time. There was a linear relationship (r = -0.80; P = 0.00001) between PTC and time of onset of TOF response.

Conclusions

There appears to be no clinical advantage in attempting to antagonize profound mivacurium-induced neuromuscular blockade.
Alterations in Spectral Characteristics of Heart Rate Variability as a Correlate of Cardiac Autonomic Dysfunction after Esophagectomy or Pulmonary Resection
Authors: Kimura Tomomasa , Komatsu Toru , Takezawa Jun , Shimada Yasuhiro
Published: November 2003

Background

Both esophagectomy and pulmonary resection are associated with postoperative cardiac complications, partly because of autonomic perturbations involving the heart. This study was undertaken to determine whether heart rate variability (HRV), employed as an index of cardiac autonomic function, changes in patients undergoing esophagectomy or pulmonary resection.

Methods

Electrocardiographic RR intervals were measured in 20 esophagectomized patients, 10 undergoing right and 10 undergoing left pulmonary resection on the preoperative day as baseline data and on postoperative days 1, 3, 5, 7, 14, and 30. Instantaneous heart rate was calculated every 250 ms from 416-s data of RR intervals. Power spectra of HRV for 128 s were computed using a fast Fourier transform and normalized by squared mean heart rate. The average ten sets of normalized HRV power were obtained by integrating the following power spectral bands: the low-, (0.06-0.10 Hz), high- (0.15-0.40 Hz), and total-frequency regions (0.01-0.40 Hz).

Results

In the esophagectomy group, mean low-, high-, and total-frequency HRV power decreased after surgery to 17%, 6%, and 15% of their preoperative values, respectively, and these indexes remained suppressed for up to 30 days. After right pulmonary resection, low- and total-frequency HRV power decreased through 30 and 7 postoperative days, respectively. In the left pulmonary resection group, HRV remained unchanged. In the esophagectomy group, mean (+/- SEM) heart rate increased from 78 (+/- 3) bpm to more than 90 bpm throughout the study, and body temperature from 36.5 (+/- 0.1) degrees C to more than 37.0 degrees C through 14 postoperative days. Heart rate and body temperature remained increased for 3 days after pulmonary surgery. Mean arterial pressure remained unchanged in the three surgical groups.

Conclusions

Reductions indicate HRV after esophagectomy or right pulmonary resection indicate a substantial and prolonged surgical injury to the autonomic nervous control of pulse rate.
In Vitro sup 31 Phosphorus-Magnetic Resonance Spectroscopy of Muscle Extracts in Malignant Hyperthermia-susceptible Patients
Authors: Payen Jean-Francois , Fouilhe Nathalie , Sam-Lai Ernest , Remy Chantal , Dupeyre Roger , Mezin Paulette , Halsall Jane , Stieglitz Paul
Published: November 2003

Background

It was recently suggested that malignant hyperthermia-susceptible (MHS) patients could have an elevated peak of phosphodiesters in leg muscles using in vivo phosphorus magnetic resonance spectroscopy. In the current study, analysis of the phosphodiesters of muscle extracts of MHS and malignant hyperthermia-negative patients was performed using in vitro phosphorus magnetic resonance spectroscopy to chemically identify and to compare the muscle concentrations of water-soluble compounds between the two groups with respect to the muscle fiber type composition.

Methods

Perchloric acid extracts of the vastus medialis muscle of seven MHS patients and ten malignant hyperthermia-negative patients on the basis of the European malignant hyperthermia contracture test were subjected to in vitro phosphorus magnetic resonance spectroscopy carried out at 9.4 T. In addition, chemical identification of the phosphodiester region and histologic examination of the muscle specimens were performed.

Results

The peak in the phosphodiester region was assigned to glycerophosphorylcholine. Muscle perchloric acid extracts of MHS patients had a significantly (P < 0.05) higher glycerophosphorylcholine to the sum of phosphocreatine and inorganic phosphate (glycerophosphorylcholine/ [phosphocreatine +inorganic phosphate]) value than those of malignant hyperthermia-negative patients. Neither a difference in the fiber type composition between the two groups nor any specific myopathy were found.

Conclusions

In the absence of histologic differences between muscle specimens of MHS and malignant hyperthermia-negative patients, these results could suggest that glycerophosphorylcholine could be a marker of an impairment in the phospholipid metabolism in the skeletal muscle of MHS patients.
Circulatory Effects of Hypoxia, Acute Normovolemic Hemodilution, and Their Combination in Anesthetized Pigs
Authors: Schou Henning , Perez de Sa Valeria , Sigurdardottir Maria , Roscher Roger , Jonmarker Christer , Werner Olof
Published: November 2003

Background

Because hemodilution decreases the oxygen-carrying capacity of blood, it was hypothesized that severe hemodilution would decrease the tolerance to alveolar hypoxia.

Methods

Hemodynamics, oxygen transport, and blood lactate concentrations were compared in ten pigs with normal hematocrit (33 +/- 4%), and ten hemodiluted pigs (hematocrit 11 +/- 1%; mean +/- SD) anesthetized with ketamine-fentanyl-pancuronium during stepwise decreases in inspired oxygen fraction (FIO2; 1.0, 0.35, 0.21, 0.15, 0.10, 0.05).

Results

Median systemic oxygen delivery (DO2SY) became critical (the DO2SY value when arterial lactate exceeded 2.0 mmol.l-1) at 10.4 ml.kg-1.min-1 (range 6.9-16.1) in hemodiluted animals and at 11.8 ml.kg-1.min-1 (5.9-32.2) in animals with normal hematocrits (NS). The relationship between mixed venous oxygen saturation and arterial lactate values was less consistent and median critical mixed venous oxygen saturation was higher (P < 0.05) in the hemodiluted group (35%, range 21-64), than in animals with normal hematocrits (21%, 7-68%). In animals with normal hematocrit, decreasing FIO2 from 1.0 to 0.10 resulted in a decrease in DO2SY from 26.3 +/- 9.1 to 9.3 +/- 3.9 ml.kg-1.min-1 (P < 0.01). Cardiac output did not change, systemic oxygen extraction ratio increased from 0.23 +/- 0.08 to 0.68 +/- 0.13 (P < 0.01), and arterial lactate from 0.9 +/- 0.2 to 3.4 +/- 3.0 mmol.l-1 (P < 0.05). Cardiac venous blood flow, as measured by retrograde thermodilution, increased from 5.7 +/- 2.9 to 12.6 +/- 5.7 ml.kg-1.min-1 (P < 0.01). When FIO2 was reduced to 0.05, three animals became hypotensive and died. In the second group, hemodilution increased cardiac output and systemic oxygen extraction ratio (P < 0.01). Cardiac venous blood flow increased from 4.1 +/- 1.7 to 9.8 +/- 5.1 ml.kg-1.min-1 (P < 0.01), and cardiac venous oxygen saturation from 22 +/- 5 to 41 +/- 10% (P < 0.01). During the subsequent hypoxia, cardiac output and DO2SY were maintained until FIO2 = 0.15 (DO2SY = 10.1 +/- 3.3 ml.kg-1.min-1). Cardiac venous blood flow was then 18.5 +/- 10.7 ml.kg-1.min-1 (P < 0.01), but in spite of this, myocardial lactate production occurred. At FIO2 = 0.10 (DO2SY = 7.7 +/- 3.0 ml.kg-1.min-1), arterial lactate concentration increased to 8.5 +/- 2.3 mmol.l-1 (P < 0.01), and most animals became hypotensive. All hemodiluted animals died when FIO2 was decreased to 0.05 (P < 0.01 when compared to animals with normal hematocrit).

Conclusions

Systemic and myocardial lactate production occurred at similar systemic oxygen delivery rates in hemodiluted and nonhemodiluted animals. Mixed venous oxygen saturation may be a less reliable indicator of inadequate oxygen delivery during hemodilution.
Atelectasis and Chest Wall Shape during Halothane Anesthesia
Authors: Warner David O. , Warner Mark A. , Ritman Erik L.
Published: November 2003

Background

Anesthesia produces atelectasis in the dependent areas of the lungs by mechanisms that remain unknown. It has been proposed that anesthesia produces a cephalad shift in the end-expiratory position of the diaphragm, which compresses the lungs and produces atelectasis. This study tested the hypothesis that the extent of atelectasis is correlated with the cephalad displacement of the dependent portion of the diaphragm produced by halothane anesthesia in healthy young human subjects.

Methods

Twelve volunteers (mean age 34 yr) were studied while awake and during approximately 1.2 minimum alveolar concentration halothane anesthesia. Chest wall configuration was determined using images of the thorax obtained by three-dimensional fast computed tomography. Functional residual capacity was measured by a nitrogen dilution technique. Measurements were performed during quiet breathing in all subjects and after paralysis with 0.1 mg/kg vecuronium and mechanical ventilation in six subjects. Atelectasis was assumed to be present in regions of the lung that showed radiographic attenuation values similar to solid organs such as the liver.

Results

Atelectasis in dependent lung regions was not apparent in scans performed while the subjects were awake. Anesthesia with spontaneous breathing increased the volume of atelectasis measured at end-expiration by more than 1 ml in 9 of 12 subjects. For all subjects, the volume of atelectasis was 29 +/- 10 ml (M +/- SE), representing 0.67 +/- 0.23% of the total thoracic volume. The distribution of atelectasis varied along the cephalocaudal axis, with less atelectasis in more cephalad transverse sections. Paralysis and mechanical ventilation significantly decreased the volume of atelectasis present at end-expiration. There was no correlation between the average amount of cephalad displacement of the most dependent region of the diaphragm and the amount of atelectasis, nor was there any correlation between the amount of atelectasis and anesthesia-induced changes in the end-expiratory position of any chest wall structure.

Conclusions

The dependent lung atelectasis produced by halothane anesthesia does not appear to be related to changes in the position of any single chest wall structure in these healthy young subjects, but rather to an interaction of several factors that remain to be identified.
Transesophageal Atrial Pacing in Anesthetized Patients with Coronary Artery Disease
Authors: Hogue Charles W. Jr. , Davila-Roman Victor G. , Pond Charles , Hauptmann Edward , Braby David , Lappas Demetrios G.
Published: November 2003

Background

Transesophageal atrial pacing (TEAP) provides prompt and precise control of heart rate and improves hemodynamics in anesthetized patients with bradycardia and hypotension. The authors' purpose in this study was to examine the hemodynamic benefits of TEAP versus the risk of myocardial ischemia in patients about to undergo coronary artery bypass surgery.

Methods

Hemodynamics, ventricular filling pressures, mixed venous oxygen saturation, and end-diastolic, end-systolic, and fractional area change of the left ventricle, determined by transesophageal echocardiography (TEE), were measured after anesthesia induction with 30 micrograms/kg fentanyl and at incremental TEAP rates of 65, 70, 80, and 90 beats/min (bpm) in 40 adult patients. Monitoring for myocardial ischemia was accomplished with 12-lead electrocardiograms and biplane TEE assessment of left ventricular regional wall motion. Hemodynamics, electrocardiograms, and TEE measurements at each TEAP rate were compared with baseline awake measurements (except TEE) and with measurements obtained after anesthesia induction before TEAP.

Results

Sinus bradycardia occurred in 15 patients after anesthesia induction and was associated with a hypotensive response and a decrease in cardiac output in 10 patients. In these patients, TEAP restored diastolic blood pressure and cardiac output to baseline values at TEAP rates of 65 and 80 bpm, respectively. Stroke volume was similar to baseline measurements after anesthesia induction and at TEAP rates of 65, 70, and 80 bpm, but was significantly reduced from baseline at TEAP 90 bpm. Myocardial ischemia was detected in 7 and 5 patients at a TEAP rate of 80 and 90 bpm, respectively.

Conclusions

Control of heart rate with TEAP restores intraoperative hemodynamics to baseline in patients in whom bradycardia and a hypotensive response develop before coronary artery bypass surgery. When using TEAP for patients with severe coronary artery disease, these results support using the lowest TEAP rate titrated to achieve optimal hemodynamics, while closely monitoring for myocardial ischemia, especially at TEAP rates > 80 bpm.
Chronic Cocaine Administration Reversibly Increases Isoflurane Minimum Alveolar Concentration in Sheep
Authors: Bernards Christopher M. , Kern Christian , Cullen Bruce F.
Published: November 2003

Background

Significant numbers of patients are seen for surgery and anesthesia with a history of chronic cocaine use. However, little is known about how cocaine use influences anesthetic physiology and pharmacology. The purpose of this study was to investigate the effect of chronic cocaine exposure on the minimum alveolar concentration (MAC) of isoflurane in sheep.

Methods

Isoflurane MAC was determined at baseline in 12 sheep using a standard protocol. The animals were subsequently exposed to cocaine for 18 days. Cocaine exposure consisted of a continuous subcutaneous cocaine infusion at 0.2 mg.kg-1.h-1, twice daily 4-mg/kg intravenous boluses and repeated hourly 4 mg/kg cocaine boluses for 8 h on day 18. Minimum alveolar concentration determinations were repeated again on days 15, 18, and on day 28 after 10 days of cocaine abstinence.

Results

Compared to baseline MAC (1.53 +/- 0.12%) cocaine exposure significantly increased isoflurane MAC on days 15 (1.91 +/- 0.14%) and 18 (1.78 +/- 0.13%; P = .005). MAC decreased after discontinuation of cocaine and was not different from baseline on day 28 (1.67 +/- 0.11).

Conclusions

In sheep, chronic cocaine exposure resulted in a reversible increase in isoflurane MAC. This finding contrasts with studies of other central nervous system stimulants, which have demonstrated a decrease in MAC after chronic drug exposure.
Effect of Propofol on Affective State as Assessed by Place Conditioning Paradigm in Rats
Authors: Pain L. , Oberling P. , Sandner G. , Di Scala G.
Published: November 2003

Background

Whether propofol produces a pleasant affective state remains unclear from clinical studies. In the current study, the effect on affective state of subanesthetic and anesthetic doses of propofol was assessed at a preclinical level with rats in a place conditioning paradigm. Propofol was compared with methohexital.

Methods

In the place conditioning paradigm, propofol-induced effect was repeatedly paired with one of two distinguishable compartments of the apparatus, whereas the vehicle-induced effect was repeatedly paired with the other compartment. During a subsequent free-choice test, a preference for the drug-paired compartment over the vehicle-paired compartment would be indicative of pleasant state induced by the drug. For all experiments, the conditioning session lasted 8 days and consisted of four pairings of the drug with one compartment and four pairings of the equivalent volume of vehicle with the other compartment. In experiment 1A, four groups of rats were designated according to the dose of propofol that they received intraperitoneally: 0,30,60, or 90 mg/kg. In experiment 1B, the same procedure was used with subanesthetic doses of intraperitoneal methohexital: 0,10,20, or 30 mg/kg. In experiment 2, the rats were conditioned during the recovery period from short-term anesthesia. For one group, anesthesia was induced by propofol (100 mg/kg) whereas for the other group, anesthesia was induced by an equivalent anesthetic dose of methohexital (40 mg/kg).

Results

In experiment 1A, the 30-mg/kg, 60-mg/kg, and 90-mg/kg groups showed a place preference for the drug-paired compartment, but only the group conditioned with 60 mg/kg propofol significantly differed from the 0-mg/kg group. In experiment 1B, the groups conditioned with methohexital showed no place preference for the drug-paired compartment. In experiment 2, the rats showed a place preference for the compartment in which they recovered from propofol-induced anesthesia but no place preference for the compartment in which they recovered from methohexital-induced anesthesia.

Conclusions

Propofol, but not methohexital, induced a pleasant affective state in rats at subanesthetic doses as well as during recovery from an anesthetic dose.
Simulation of an Epidural Test Dose with Intravenous Isoproterenol in Awake and in Halothane-anesthetized Children
Authors: Kozek-Langenecker Sibylle , Chiari Astrid , Semsroth Margot
Published: November 2003

Background

An epidural test dose containing epinephrine does not reliably produce hemodynamic responses in children under halothane anesthesia. The purpose of this study was to determine hemodynamic responses to intravenous isoproterenol in both awake and halothane-anesthetized children.

Methods

After obtaining institutional review board approval and parental informed consent, 72 ASA physical status 1 or 2 children (2.8 +/- 1.7 yr) undergoing elective minor surgery were studied before and during anesthesia with 1.2 minimum alveolar concentration halothane. A bolus containing 0.25 mg/ kg bupivacaine and 0.05 microgram/kg, 0.075 microgram/kg, or 0.1 microgram/kg isoproterenol, or bupivacaine and saline was injected via a peripheral arm vein to simulate intravascular injection of an epidural test dose.

Results

Before induction of anesthesia, all patients showed a positive test response after isoproterenol injection (heart rate increase > or = 20 beats/min). During anesthesia, 79% of patients receiving 0.05 microgram/kg, 89% of patients receiving 0.075 microgram/kg, and 100% of patients receiving 0.1 microgram/kg met the criterion of a positive test response. Among each treatment group, all infants showed a positive test response. Blood pressure did not differ among the groups at any time. Transient benign dysrhythmias occurred in only one patient under halothane anesthesia receiving 0.075 microgram/kg isoproterenol.

Conclusion

Isoproterenol at a dose of 0.1 microgram/kg is a sensitive indicator for intravascular injection of a test dose in children anesthetized with halothane and nitrous oxide. Isoproterenol at a dose of 0.05 microgram/kg approximates a minimal effective dose in awake children and in infants. After detailed studies on neural toxicity, isoproterenol could be of value as an epidural test agent in children.
Interaction between Intrathecal Neostigmine and Epidural Clonidine in Human Volunteers
Authors: Hood David D. , Mallak Kathryn A. , Eisenach James C. , Tong Chuanyao
Published: November 2003

Background

alpha 2-Adrenergic agonists are thought to produce analgesia, in part, by activating spinal acetylcholine release. The purpose of the current study was to examine the interaction between intrathecal neostigmine and epidural clonidine for analgesia and side effects in humans.

Methods

A total of 58 volunteers received an intrathecal injection of 5% dextrose in normal saline (D5NS) or neostigmine (50, 100, or 200 micrograms in D5NS), followed in 1 h by epidural saline or clonidine (computer-controlled infusion targeted to 50, 100, 200, or 400 ng/ml in cerebrospinal fluid) using an isobolographic design. Visual analog scale pain to a noxious cold stimulus, nausea, weakness, sedation, and other safety variables was measured before and at specified intervals after drug administration.

Results

The first 21 volunteers randomized to receive intrathecal hyperbaric neostigmine rather than D5NS received the drug while in the sitting position, and had none-to-minimal analgesia 1 h later. The remaining volunteers received the drug while in the lateral position, and demonstrated dose-dependent analgesia in the foot 1 h later. Epidural clonidine also caused dose-dependent analgesia. The combination of neostigmine and clonidine resulted in an additive enhancement for analgesia, but no enhancement of each drug's side effects, and a reduction in clonidine-induced hypotension. Neostigmine injected into subjects in the lateral position diminished clonidine-induced reductions in blood pressure and plasma norepinephrine.

Conclusion

These results support enhancement of alpha 2-adrenergic analgesia by intrathecal neostigmine, but do not demonstrate synergy, as observed in animals. Lack of enhancement of side effects suggests this combination may be clinically useful.