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Clinical Science  |   December 1999
Beneficial Effects from β-Adrenergic Blockade in Elderly Patients Undergoing Noncardiac Surgery 
Author Affiliations & Notes
  • Michael Zaugg, M.D.
    *
  • Thomas Tagliente, M.D., Ph.D.
  • Eliana Lucchinetti, M.S.
  • Ellis Jacobs, Ph.D.
    §
  • Marina Krol, Ph.D.
  • Carol Bodian, Dr.P.H.
    #
  • David L. Reich, M.D.
    **
  • Jeffrey H. Silverstein, M.D.
    ††
  • *Research Fellow, Anesthesiology. †Clinical Associate Professor of Anesthesiology ‡Research Associate, Anesthesiology. §Research Associate Professor of Pathology. ∥Research Assistant Professor of Anesthesiology. #Associate Professor of Biomathematical Sciences. **Professor of Anesthesiology. ††Assistant Professor of Anesthesiology, Surgery, Geriatrics and Adult Development. From The Departments of Anesthesiology, Surgery, Geriatrics and Adult Development, Pathology and Biomathematical Sciences, The Mount Sinai School of Medicine, New York, New York, and the Anesthesia Section, Bronx Veterans Affairs Medical Center, Bronx, New York. Submitted for publication December 2, 1998. Accepted for publication July 15, 1999. Support was provided solely from institutional and/or departmental sources. Presented in part at the annual meeting of the American Society of Anesthesiologists, Orlando, Florida, October 20, 1998, and the International Anesthesia Research Society annual meeting, Los Angeles, California, March 16, 1999.
Article Information
Clinical Science
Clinical Science   |   December 1999
Beneficial Effects from β-Adrenergic Blockade in Elderly Patients Undergoing Noncardiac Surgery 
Anesthesiology 12 1999, Vol.91, 1674. doi:
Anesthesiology 12 1999, Vol.91, 1674. doi:
REDUCED myocardial ischemia 1,2 and improved long-term cardiovascular outcomes 3 occur with perioperative β-blockade. The mechanisms underlying these beneficial effects are unclear. Attenuation of the excitotoxic effects of perioperative stress hormones, with the potential for inducing myocardial injury, may underlie the cardioprotective effects of β-blockade. 4–6 β-Adrenergic antagonists have also been shown to potentiate minimum alveolar concentration for volatile anesthetics and decrease nociception in a variety of experimental settings, suggesting the potential to decrease intraoperative anesthetic requirements. 7,8 Perioperative β-blockade, however, is relatively underused, particularly in elderly patients. 9 The reluctance to use perioperative β-blockade appears to be based on concerns of producing hemodynamic instability, bronchospasm, and postoperative congestive heart failure. 10 
This controlled study of elderly surgical patients was designed to evaluate two different anesthetic regimens incorporating β-blockade for their ability to ameliorate the perioperative stress response as measured by circulating hormone levels. It was hypothesized that perioperative treatment with atenolol would modulate the neuroendocrine stress response to anesthesia and surgery, suggesting a potential mechanism for the previously reported improved cardiovascular outcome in β-blocked patients. In addition, the impact of perioperative β-blockade on several aspects of intraoperative management and postoperative recovery was determined. These secondary end points included an assessment of hemodynamic stability, adequacy of anesthetic depth, anesthetic and analgesic requirements, recovery from anesthesia, and myocardial damage as indicated by the release of cardiac troponin I.
Materials and Methods 
With institutional review board approval and written informed patient consent, 63 patients 65 yr of age or older scheduled for elective major noncardiac surgery were enrolled in one of following three groups in this randomized, prospective, open-label trial:
  • Group I: Perioperative management without atenolol or any other β-adrenergic blocking drugs.

  • Group II: Pre- and postoperative administration of atenolol.

  • Group III: Intraoperative administration of atenolol.

Inclusion criteria included being scheduled for major elective noncardiac surgery that necessitated general endotracheal anesthesia and being 65 yr of age or older. Exclusion criteria included (1) preoperative treatment with β-adrenergic agonists, β-adrenergic antagonists, or glucocorticoids;(2) second- or third-degree heart block;(3) a nonsinus rhythm seen on an electrocardiogram (ECG);(4) clinically significant congestive heart failure or bronchospasm;(5) systemic infection;(6) surgery within the previous month;(7) neurologic disorders and current use of anticonvulsant or other psychoactive medications.
The study period included the immediate preoperative period through 72 h after surgery. All data were analyzed at the conclusion of the study.
Before surgery, all patients underwent a routine clinical evaluation that included detailed medical history, physical examination, laboratory tests, 12-lead electrocardiography (ECG), and chest radiography. Three separate preoperative measurements of arterial blood pressure (systolic, diastolic, and mean arterial pressure [MAP]) obtained on the ward established individual baseline values. Approximately 1 h before surgery, a radial artery cannula was inserted during local anesthesia after the patient received 50–100 μg fentanyl. Baseline blood samples were drawn 10 min later. No other premedication was administered.
Anesthetic Management 
In all groups, anesthesia was induced with fentanyl (100–250 μg), propofol (1.7 mg/kg lean body mass) and rocuronium (0.8 mg/kg). Anesthesia was maintained with isoflurane, 66% nitrous oxide in oxygen, and continuous infusions of fentanyl (1 to 2 μg · kg−1· h−1)and rocuronium. All groups were managed to maintain MAP within 20% of preoperative values and a heart rate (HR) between 50–80 beats/min. The methodology for each group is described subsequently. Treatment algorithms were specified in advance to ensure perioperative control of hemodynamic parameters. Hypotension was treated with phenylephrine and hemodynamically significant bradycardia was treated with atropine. Normovolemia and normothermia were maintained. Figure 1shows the intravenous administration of atenolol for each group.
Fig. 1. Schematic diagram of intravenous atenolol administration for each group. 
Fig. 1. Schematic diagram of intravenous atenolol administration for each group. 
Fig. 1. Schematic diagram of intravenous atenolol administration for each group. 
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Group I. 
Intraoperative HR and MAP were maintained by adjusting the fentanyl infusion or the isoflurane concentration. No β-adrenergic agonists or antagonists were administered at any time during the study.
Group II. 
The following criteria were necessary before each atenolol dose: an HR of 55 beats/min or more; a systolic arterial pressure of 100 mmHg or more; absence of congestive heart failure, second- or third-degree heart block, and bronchospasm. Atenolol, 5 mg intravenous over 5 min, was administered approximately 30 min before the induction of anesthesia. A second dose of 5 mg atenolol was administered 5 min later if the criteria still were met. No intraoperative β-adrenergic agonists or antagonists were administered. Intraoperative HR and MAP were maintained by adjusting the fentanyl infusion or the isoflurane concentration. Fentanyl and isoflurane doses were not constrained. Atenolol doses were repeated at arrival in the postanesthesia care unit (PACU), with subsequent similar dosing every 12 h starting on the first postoperative day and continuing until 72 h after surgery.
Group III. 
Fentanyl was administered at 1 to 2 μg · kg−1· h−1. Isoflurane was limited to a maximum allowed end-tidal concentration of 0.4 volume percentage. After this dose was reached, atenolol was administered in 5-mg increments intravenously every 5 min to maintain an HR less 80 beats/min and a MAP within 20% of the preoperative MAP. No β-adrenergic agonists or antagonists were administered during the pre- or postoperative period.
Monitoring 
Intraoperative monitoring included measurement of invasive arterial blood pressure, performance of five-lead ECG with continuous ST-segment monitoring (leads II and V5), measurement of pulse oximetry, and measurement of esophageal temperature (Merlin System, Hewlett-Packard, Waltham, MA). End-tidal carbon dioxide level and inhaled anesthetics concentrations were measured by mass spectroscopy (PPG Biomedical, Pittsburgh, PA). Data were acquired every 15 s by a computerized anesthesia record-keeping system (CompuRecord, Anesthesia Recording, Pittsburgh, PA). Bispectral analysis of the electroencephalogram was performed using the A-1050 monitoring system (Aspect Medical Systems, Natick, MA). The A-1050 computes an index ranging from 0 (deeply anesthetized) to 100 (fully awake). Bispectral analysis data were acquired every 5 s beginning shortly before induction of anesthesia until eye opening.
Laboratory Analysis 
Blood samples were collected at the following time points:(1) preinduction;(2) intubation + 4 min;(3) incision + 4 min;(4) incision + 60 min;(5) 15 min after arrival in the PACU; and (6) 24 h and (7) 72 h after surgery. Arterial samples were obtained in the operating room and PACU and venous samples were obtained at the surgical ward. The samples were placed on ice immediately and the serum or plasma was separated using a refrigerated centrifuge. Aprotinin (50 μl, Bayer-Miles Laboratories, Kankakee, IL) was added to the samples used for adrenocorticotropic hormone (ACTH) and neuropeptide Y (NPY) determinations. All specimens were immediately frozen (−80°C) until analyzed.
Norepinephrine, epinephrine, NPY, ACTH, and cortisol measurements were performed by laboratory technicians blinded to the study group assignments. The following radioimmunoassays were used: norepinephrine and epinephrine (American Laboratory Products Company, Windham, NH): mean minimum detectable concentration (MMDC) for norepinephrine 15 pg/ml, for epinephrine 5 pg/ml; NPY (Advance Chemical Technology, Louisville, KY): MMDC 1 nmol/ml; ACTH (Incstar, Stillwater, MN): MMDC 15 pg/ml; cortisol (ICN Biomedicals, Costa Mesa, CA): MMDC 0.15 μg/ml. Cardiac troponin I (cTnI) levels were determined by fluorometric assay (Stratus II analyzer; Dade International, Miami, FL): MMDC 0.35 ng/ml. The following prespecified criteria were used to evaluate cTnI levels: < 0.40 ng/ml = normal range for healthy individuals; 0.40–1.49 ng/ml = myocardial damage (micronecrosis), ≥ 1.5 ng/ml = myocardial infarction (sensitivity, 93%; specificity, 99%).
Analysis of Clinical Data 
To eliminate artifactual data, 2-min medians were computed off-line. Statistical analysis was performed on consecutive 15-s averages of HR, ST-segment changes, and blood pressure and end-tidal isoflurane concentration and from 24 consecutive 5-s samples for the bispectral analysis data. Intraoperative blood pressure and HR were compared between groups using a previously described lability index. 11 Absolute fractional changes between consecutive 2-min medians (between times x  and x  + 2 min) for HR and MAP were calculated according to the formulawhere V is the 2-min median HR or MAP. A lability index for MAP was defined as an ‖FCM‖ > 0.06 for MAP. A lability index for HR was defined as an ‖FCM‖ > 0.15. The higher the lability index, the greater the instability in the measured variable.
The times from discontinuation of isoflurane to extubation and to orientation in the PACU (the ability to state date of birth) were recorded. Administered fentanyl doses for induction and maintenance were recorded and reported as μg · kg−1· h−1of anesthesia. Total administered dose of morphine in the PACU and pain scores (visual analog scale score 0–10) 30 min after arrival in the PACU also were recorded. Suitability for PACU discharge was assessed every 10 min by a study physician and at least two PACU nurses who were blinded to study group assignments. The following discharge criteria were used: stable vital signs, satisfactory level of alertness (modified Observer's Assessment of Alertness/Sedation Scale score ≥ 4), 12 adequate pain control (visual analog scale score ≤ 3), and arterial oxygen saturation greater than or equal to preoperative values (at room air).
Data from patients receiving postoperative epidural analgesia were excluded from analyses of pain scores, suitability for PACU discharge, and morphine usage. Patients who were transferred directly from the operating room to the intensive care unit were excluded from data analysis for recovery.
Medical charts were reviewed and the caregivers were interviewed daily for the occurrence of any adverse events. Physical examinations and interviews, including a semistructured interview to determine explicit intraoperative memory, were performed in the PACU and at 24, 48, and 72 h after surgery. A 12-lead ECG was obtained at least once for each patient postoperatively and interpreted by an anesthesiologist and a cardiologist blinded to group assignment.
Hemodynamic instability was defined by prespecified criteria: systolic arterial pressure less than 90 or greater than 180 mmHg, HR less than 40 or more than 100 beats/min. Clinically diagnosed adverse cardiac outcomes (as opposed to the cTnI measurements) were defined as myocardial infarction (new Q wave, persistent ST–T wave changes as defined by Minnesota Codes, 13 association with any elevation of creatine kinase with creatine kinase MB [muscle–brain] increase > 5%), congestive heart failure (pulmonary edema diagnosed by chest radiography or at least two of the following symptoms: shortness of breath and rales, cardiomegaly, S3gallop, jugular venous distention, and peripheral edema diagnosed by an independent managing clinician); and cardiac death, as defined by standard criteria. 13 Intraoperative ischemic episodes were defined as new horizontal or downsloping ST-segment depressions greater than or equal to 0.1 mV, persisting 60 ms or more after the J point, or ST-segment elevations of 0.2 mV or more lasting more than 2 min. With ST depression at baseline, a further depression of 0.15 mV or more from that baseline was necessary.
Statistical Analysis 
The sample size was calculated based on published data for NPY levels. 14,15 With an expected difference of 10 nmol/ml between group means, a standard deviation of 10 nmol/ml in each group, an α= 0.05/3, and a β= 0.8, a sample size of 20 patients per group was necessary. A logarithmic transformation was applied to all hormone data to ensure a normal distribution before statistical analysis. Repeated-measures analysis of variance (with the Bonferroni correction) was used to evaluate differences over time between groups for the hormonal and hemodynamic data. Multiple t  tests were used to compare the hormonal and hemodynamic data at each time point with the respective preoperative baseline measurements. Appropriate corrections for multiple comparisons were applied to the P  values (Bonferroni correction). All other data were analyzed using an analysis of variance for parametric data or Kruskal–Wallis tests for nonparametric data. Appropriate post hoc  procedures were used to isolate between-group differences, as indicated in the tableand figure legends. Categoric data were analyzed using the two-tailed Fisher exact test. Analyses were performed using StatXact-3 software (Cytel Software, Cambridge, MA) for categoric data, all other analyses were performed using StatView software (Abacus Concepts, Berkeley, CA).
Results 
Patient characteristics are listed in table 1. The three groups were similar (no significant differences) with respect to the type and duration of surgery. All patients were found to have coronary artery disease or to manifest at least two risk factors for coronary artery disease, as previously defined by Mangano et al.  3 Seventy-three percent of patients had preexisting ST-segment alterations. Data from the four patients who were withdrawn from the study were not included in the analysis (table 1).
Table 1. Patient Characteristics 
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Table 1. Patient Characteristics 
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Neuroendocrine Stress Response 
Peak levels of norepinephrine, epinephrine, ACTH, and cortisol occurred in the PACU or at 24 h postoperatively in all groups (table 2). Norepinephrine levels tended to remain elevated during the entire study period; the other stress parameters returned to baseline levels before 72 h after surgery. Peak NPY levels occurred intraoperatively 1 h after incision, remained elevated in the PACU, and returned to (group I) or decreased below (groups II and III) baseline levels by 72 h. No statistically significant difference in the time course of the neuroendocrine response between groups was observed for norepinephrine, epinephrine, NPY, or cortisol. ACTH levels were lower in patients in group III (table 2).
Table 2. Perioperative Neuroendocrine Stress Response 
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Table 2. Perioperative Neuroendocrine Stress Response 
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Hemodynamic Responses 
An overview of the intraoperative and postoperative HR and systolic rate-pressure product (RPP) at various time points is presented in figures 2 and 3. During emergence and extubation, HR and RPP were significantly lower in patients in groups II and III. HR and RPP remained significantly below preoperative values up to 72 h after surgery for groups II and III. In patients in group I, HR but not RPP remained significantly increased up to 72 h after surgery.
Fig. 2. Heart rate (HR, mean ± SD) at the various time points for each anesthetic group. Repeated-measures analysis of variance (  P  = 0.035) indicated that the groups differed in HR over time. Differences between groups were analyzed using the Bonferroni–Dunn  post hoc  test (with  P  < 0.017 significant): group I  versus  II,  P  = 0.014; group I  versus  III,  P  = 0.001; group II  versus  III,  P  = 0.80. Paired  t  tests with Bonferroni correction for multiple comparisons (with  P  < 0.01 significant) were used to compare HR at each time point with the respective preoperative baseline value for each group. *Significantly increased compared to baseline values;**Significantly decreased compared to baseline values. 
Fig. 2. Heart rate (HR, mean ± SD) at the various time points for each anesthetic group. Repeated-measures analysis of variance (  P  = 0.035) indicated that the groups differed in HR over time. Differences between groups were analyzed using the Bonferroni–Dunn  post hoc  test (with  P  < 0.017 significant): group I  versus  II,  P  = 0.014; group I  versus  III,  P  = 0.001; group II  versus  III,  P  = 0.80. Paired  t  tests with Bonferroni correction for multiple comparisons (with  P  < 0.01 significant) were used to compare HR at each time point with the respective preoperative baseline value for each group. *Significantly increased compared to baseline values;**Significantly decreased compared to baseline values. 
Fig. 2. Heart rate (HR, mean ± SD) at the various time points for each anesthetic group. Repeated-measures analysis of variance (  P  = 0.035) indicated that the groups differed in HR over time. Differences between groups were analyzed using the Bonferroni–Dunn  post hoc  test (with  P  < 0.017 significant): group I  versus  II,  P  = 0.014; group I  versus  III,  P  = 0.001; group II  versus  III,  P  = 0.80. Paired  t  tests with Bonferroni correction for multiple comparisons (with  P  < 0.01 significant) were used to compare HR at each time point with the respective preoperative baseline value for each group. *Significantly increased compared to baseline values;**Significantly decreased compared to baseline values. 
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Fig. 3. Systolic rate-pressure product (RPP, mean ± SD) values at various time points for each anesthetic group. Repeated-measures analysis of variance (  P  = 0.02) indicated that the groups differed in RPP over time. Differences between groups were analyzed using the Bonferroni–Dunn  post hoc  test (  P  < 0.017 is significant): group I  versus  II,  P  = 0.016; group I  versus  III,  P  < 0.0001; group II  versus  III,  P  = 0.10. Paired  t  tests with Bonferroni correction for multiple comparisons (with  P  < 0.01 significant) were used to compare RPP at each time point with the respective preoperative baseline value for each group. *Significantly increased compared with baseline values. **Significantly decreased compared with baseline values. 
Fig. 3. Systolic rate-pressure product (RPP, mean ± SD) values at various time points for each anesthetic group. Repeated-measures analysis of variance (  P  = 0.02) indicated that the groups differed in RPP over time. Differences between groups were analyzed using the Bonferroni–Dunn  post hoc  test (  P  < 0.017 is significant): group I  versus  II,  P  = 0.016; group I  versus  III,  P  < 0.0001; group II  versus  III,  P  = 0.10. Paired  t  tests with Bonferroni correction for multiple comparisons (with  P  < 0.01 significant) were used to compare RPP at each time point with the respective preoperative baseline value for each group. *Significantly increased compared with baseline values. **Significantly decreased compared with baseline values. 
Fig. 3. Systolic rate-pressure product (RPP, mean ± SD) values at various time points for each anesthetic group. Repeated-measures analysis of variance (  P  = 0.02) indicated that the groups differed in RPP over time. Differences between groups were analyzed using the Bonferroni–Dunn  post hoc  test (  P  < 0.017 is significant): group I  versus  II,  P  = 0.016; group I  versus  III,  P  < 0.0001; group II  versus  III,  P  = 0.10. Paired  t  tests with Bonferroni correction for multiple comparisons (with  P  < 0.01 significant) were used to compare RPP at each time point with the respective preoperative baseline value for each group. *Significantly increased compared with baseline values. **Significantly decreased compared with baseline values. 
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Intraoperative hemodynamic control was satisfactory in all groups (table 3). The percentage of time for which MAP remained less than 60 mmHg or HR remained less than than 50 beats/min was similar across groups. Compared with patients in group I, a significant decrease in the percentage of time HR remained at more than 80 beats/min was observed for patients in group III (P  = 0.006;table 3). Lability indices for HR and MAP (table 3), which describe the instability of the measured variable, and the incidences of atropine and phenylephrine use (table 4) were similar for the three groups.
Table 3. Intraoperative Hemodynamic Responses: Percent of Total Anesthesia Time 
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Table 3. Intraoperative Hemodynamic Responses: Percent of Total Anesthesia Time 
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Table 4. Intraoperatively Administered Medication 
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Table 4. Intraoperatively Administered Medication 
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The incidence of perioperative hemodynamic abnormalities is presented in table 5. Episodes of hypotension (systolic arterial pressure < 90 mmHg) occurred in all three groups. Notably, the number of patients with postoperative tachycardia (HR > 100 beats/min) was significantly increased in group I compared with groups II and III (table 5).
Table 5. Incidence of Perioperative Hemodynamic Abnormalities 
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Table 5. Incidence of Perioperative Hemodynamic Abnormalities 
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Anesthetic Doses and Recovery from Anesthesia 
All patients in group II received 10 mg intravenous atenolol preoperatively and at each scheduled postoperative dose. Patients in group III received a median dose of 20 mg atenolol intravenously, with a minimum of 10 mg and a maximum of 80 mg. Administered doses of anesthetic agents were significantly different among groups (table 4). By design, patients in group III received less isoflurane. On average, patients in group III received 37.5% less isoflurane than patients in groups I and II (P  = 0.003). Patients in groups II and III received 27.7% less fentanyl than group I patients (P  < 0.0001;table 4). Despite the differences in anesthetic doses, depth of anesthesia, as indicated by average bispectral analysis values, was similar in all three groups (group I: 54 ± 11; group II: 53 ± 10; group III 58 ± 2; analysis of variance P  = 0.50). No reports of intraoperative recall were elicited from any patient.
Patients in groups II and III had significantly shorter early recovery times and met prospectively defined PACU discharge criteria sooner than patients in group I patients (table 6). Total morphine doses and pain scores in the PACU also were significantly lower in groups II and III (table 6).
Table 6. Recovery Data 
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Table 6. Recovery Data 
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Cardiac Troponin I and Cardiovascular Outcome 
None of the patients experienced any adverse cardiac event as assessed by routine clinical examination. Specifically, no episodes of intraoperative myocardial ischemia were detected intraoperatively or during retrospective review of the computerized ST-segment data. Postoperative 12-lead ECGs were evaluated for all patients and revealed no evidence of new postoperative myocardial ischemia or infarction.
No patient had detectable levels of cTnI preoperatively. Perioperative release of cTnI (≥ 0.4 ng/ml) was detected in 8 of 19, 4 of 20, and 5 of 20 patients in groups I, II, and III, respectively (fig. 4). Peak levels of cTnI occurred intraoperatively in 6 patients (two from each group) and postoperatively in 11 patients (group I: 6; group II: 2; group III: 3). Three patients in group I were found to have a clinically unrecognized postoperative myocardial infarction if the prespecified cTnI level more than 1.5 ng/ml was used to indicate myocardial infarction.
Fig. 4. Cardiac troponin I (cTnI) levels for patients in each anesthetic group. Peak levels of cTnI (only the highest level for each patient is presented) measured during the perioperative period are presented. Values are presented as nanograms/milliliter serum. Values above 0.4 ng/ml (  lower  ) are indicative of micronecrosis. Values above 1.5 ng/ml (  upper  ) are indicative of myocardial infarction. 
Fig. 4. Cardiac troponin I (cTnI) levels for patients in each anesthetic group. Peak levels of cTnI (only the highest level for each patient is presented) measured during the perioperative period are presented. Values are presented as nanograms/milliliter serum. Values above 0.4 ng/ml (  lower  ) are indicative of micronecrosis. Values above 1.5 ng/ml (  upper  ) are indicative of myocardial infarction. 
Fig. 4. Cardiac troponin I (cTnI) levels for patients in each anesthetic group. Peak levels of cTnI (only the highest level for each patient is presented) measured during the perioperative period are presented. Values are presented as nanograms/milliliter serum. Values above 0.4 ng/ml (  lower  ) are indicative of micronecrosis. Values above 1.5 ng/ml (  upper  ) are indicative of myocardial infarction. 
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The 11 patients with postoperative increases in cTnI of 0.4 ng/ml or more had slightly but significantly higher postoperative HRs compared with patients without increases in cTnI (68 ± 14 vs.  78 ± 15 beats/min; analysis of variance P  = 0.002). No correlation was found between hormonal markers of the neuroendocrine stress response and cTnI levels.
Discussion 
The sympathetic neuroendocrine profiles (NPY, norepinephrine, and epinephrine) of the three anesthetic regimens were indistinguishable. The ACTH response was decreased in both β-blocker groups; however, cortisol levels were unaffected. Therefore, our principal hypothesis is rejected. Although our sample sizes were small, the study had an 80% statistical power to (and did) detect a minimum difference of 10 nmol/ml NPY in the average value between groups, which is the minimum difference we consider to be clinically significant. Both the pattern of peak concentrations for all measured hormones and the magnitude of responses of our patients are similar to previous reports in younger patients. 16,17 By design, less fentanyl (groups II and III) and isoflurane (group III) were necessary if atenolol was administered. Stress hormone levels would be expected to rise with decreasing doses of anesthetic agents. 18 However, neither neuroendocrine nor hemodynamic evidence of light anesthesia were present in any patient. Consistent with these findings, previous work indicates that esmolol reduces anesthetic requirements, 7,19 and propranolol potentiates opioid analgesia. 20 β-Adrenergic antagonists possess central nervous system–depressant antinociceptive and anxiolytic effects 7,21,22 thought to be caused by central β-blockade, although hydrophilic, esmolol, and atenolol attain plasma and cerebrospinal fluid ratios similar to those of lipophilic β-blockers. 23 
Classically, stress responses are subserved by the hypothalamic pituitary axis and the sympathetic nervous system. 24 The choice of anesthetic technique can significantly effect stress hormone responses, 25,26 and thus measurement of these responses became an important means for comparing techniques. 27,28 General anesthesia is thought to affect stress responses through action on the central nervous system, including the spinal cord. 29,30 Although β-antagonists are thought to act principally on peripheral receptors, they also have substantial anesthetic-modulating central effects. 7,21,22 We hypothesized that the addition of β-adrenergic blockade to an anesthetic regimen would significantly modulate humoral stress responses. A corollary of this hypothesis is that, in the absence of such modulation, humoral stress responses would increase in magnitude if alteration in the heart rate and blood pressure were blocked at a peripheral level.
Circulating hormone concentrations represent a composite of direct secretion, neural overflow, metabolism, excretion, and regional variations in hormone activity. 31 Norepinephrine in plasma largely represents the transmitter released by sympathetic nerves that has spilled over into the circulation. 32 In addition to releasing norepinephrine, sympathetic postganglionic neurons release neuropeptides. In particular, cells that release both norepinephrine and NPY innervate blood vessels, 33,34 particularly in the coronary circulation. 34 Tachycardia, left-ventricular failure, 35 and angina 36 are associated with increased NPY levels in cardiac patients. Thus, we selected NPY as our principle variable. Glucocorticoid levels were measured to assess hypothalamic–pituitary–adrenal activity and ensure that a stress response had occurred.
The group II regimen was modified from Mangano et al.  , 3 principally by limiting the postoperative administration of atenolol to 3 days. This was consistent with our average duration of stay for the elderly patients included in this study but still allowed a certain degree of comparison to their larger study that included outcome measures. The group III regimen offers the advantage of easy integration into anesthetic care paradigms. In comparison, group II necessitated clinical monitoring and evaluation in the postoperative period, which was in addition to standard nursing workloads.
Control of Hemodynamic Responses 
Maintenance of intraoperative hemodynamic parameters within prespecified limits was achieved with all three anesthetic regimens. The use of pre- and intraoperative (up to 80 mg) atenolol was well-tolerated. The incidence of significant bradycardia was not increased in the atenolol-treated patients, even if atenolol was combined with fentanyl and phenylephrine, which are known to provoke bradycardia. β-Blockade significantly reduced the incidence of tachycardia and high RPP, particularly during emergence and extubation and in the postoperative period, times which have been associated with increased hemodynamic instability and myocardial ischemia. 2,37 The hemodynamic effects of atenolol in group III patients persisted up to 72 h postoperatively. The expected duration of activity of atenolol (24 h); decreased perioperative renal clearance, particularly in elderly patients; and increased vagal tone after higher doses of atenolol may have contributed to this prolonged effect. 38 These data suggest that peri- and intraoperative administration of atenolol is safe, effective, and well-tolerated by elderly patients with significant coexisting diseases.
Anesthetic Doses and Recovery from Anesthesia 
By design, group III patients received the lowest doses of isoflurane. Nonetheless, satisfactory levels of unconsciousness were achieved in all patients. The bispectral analyses were similar across groups and were within the range in which lack of recall is expected. 39 This is consistent with reports of satisfactory levels of unconsciousness produced by lower doses of volatile anesthetics than are necessary to control HR and blood pressure during surgical stimulation. 18,40,41 
More rapid recovery from anesthesia and reduced postoperative analgesic requirements were observed in the β-blocker groups. Significantly faster recovery was reported previously in patients receiving metoprolol and halothane anesthesia. 42 The magnitude of these differences warrants further investigation and may portend a significant clinical advantage, particularly for elderly surgical patients.
Myocardial Damage 
β-Blockade has been studied as a means of decreasing myocardial ischemia and improving cardiac outcomes. 1,3 We selected cTnI as a surrogate for long-term cardiac outcomes. cTnI is unique to myocardium, and circulating levels of cTnI are not normally detectable. In patients with acute coronary syndromes, progressively increasing levels of cTnI are associated with an increased risk of death, presumably because of the increased amount of myocardial necrosis. 43 Detectable circulating levels of cTnI (> 0.35 ng/ml) below those used to define myocardial infarction are indicative of myocardial damage. 44,45 For the current assay, myocardial infarction was defined as cTnI level > 1.5 ng/ml. Lower levels of cTnI than measured in the current study have been associated with myocardial damage in congestive heart failure. 45 Increased cTnI level, consistent with myocardial damage, was present in 29% of our patients (17 of 59): 42% of group I patients, 20% of group II patients, and 25% of group III patients. The lack of statistical significance may represent a type II statistical error. However, the large percentage of patients exhibiting these levels suggests that this is not a rare event and warrants further investigation in a larger prospective study to determine the ultimate usefulness of cTnI as a surrogate for cardiac outcome.
Several previous studies have explored perioperative β-blockade and its effect on myocardial ischemia in noncardiac surgery. Stone et al.  1 administered a single oral preoperative dose of β-blockers to patients with mild, uncontrolled hypertension. The incidence of myocardial ischemia was 28% in the untreated controls compared with 2% in the β-blocker–treated patients based on ECG criteria derived from a V5lead. Wallace et al.  2 administered intravenous atenolol preoperatively and intravenous or oral atenolol for up to 7 days postoperatively in patients with or at risk for coronary artery disease. The regimen was similar to group II in this study; however, Mangano et al.3and Wallace et al.2continued atenolol treatment for the duration of the hospital stay. Intraoperative myocardial ischemia was reported to be 18% in the control group and 12% in the β-blocker–treated group, which did not reach statistical significance. Postoperative ischemia over days 0–7, however, was significantly decreased in the β-blocker–treated group (24 vs.  39%). In the current study, no myocardial ischemia was detected by clinicians intraoperatively. A retrospective review of the computerized continuously recorded ST-segment data also failed to detect any episodes of intraoperative myocardial ischemia. In the postoperative period, a 12-lead ECG was obtained at least once for each patient, again failing to detect criteria for new myocardial ischemia. Several factors may explain these differences. Most important, previous studies excluded patients with left bundle branch block, digoxin effects, or ECG evidence of left-ventricular hypertrophy and strain, characteristics that obscure the ECG diagnosis of myocardial ischemia. In the current study a large percentage of patients (43 patients, 73%) showed preexisting ECG changes that complicated the diagnosis of myocardial ischemia. Thus, the ECG may under-report episodes of myocardial ischemia in our patients.
Limitations 
Although the treating anesthesiologists were not blinded to group assignment, intraoperative management was directed at titrating HR and blood pressure to prespecified criteria. Because the hemodynamic effects of intravenous atenolol are relatively transparent and the incorporation of a placebo infusion would delay treatment of intraoperative hypertension and tachycardia, we thought that blinding was not justified. Because prespecified criteria were used, clinical care should have been affected only marginally. In addition, the observations in the postoperative period were blinded.
A limited number of parameters were used to assess the impact of β-blockade on the hormonal stress response; inflammatory and immunomodulatory parameters were not assessed. 46 The predictive value of perioperative cTnI levels for cardiac morbidity and mortality rates remains to be validated. All enrolled patients had either documented coronary artery disease or two or more risk factors for coronary artery disease. Such risk factors are common among geriatric patients. Nonetheless, it is not clear that our results would be applicable to elderly patients with no risk factors. A significantly larger clinical trial with long-term follow-up is necessary to address these issues.
In a recent editorial, Warltier 9 stated that “overwhelming” evidence demonstrated the beneficial effects of β-blockade in patients at risk for coronary artery disease and speculated that the relative underuse of these drugs resulted from misperceptions regarding the risk:benefit ratio for patients. The current study particularly emphasizes the idea that the perioperative use of β-blockers can decrease the amount of anesthetic administered to elderly surgical patients at risk for cardiovascular complications without altering the neuroendocrine response to surgery. A lack of alteration in neuroendocrine responses was associated with improved hemodynamic stability and faster recovery from anesthesia. Finally, our current data regarding perioperative cTnI levels are consistent with previous reports of decreased myocardial ischemia and suggest that β-blockade might reduce the incidence of perioperative microinfarctions.
The authors thank Dade International, Miami, Florida, for providing the assay for cTnI;, Aspect Medical Systems, Natick, Massachusetts, for providing the A-1050 monitor; and the anesthesiologists, surgeons, and PACU nurses who assisted in this project.
References 
References 
Stone JG, Foex P, Sear JW, Johnson LL, Khambatta HJ, Triner L: Myocardial ischemia in untreated hypertensive patients: Effects of a single small oral dose of a beta-adrenergic blocking agent. A NESTHESIOLOGY 1988; 68: 495–500
Wallace A, Layug B, Tateo I, Li J, Hollenberg M, Browner W, Miller D, Mangano DT: Prophylactic atenolol reduces postoperative myocardial ischemia. A NESTHESIOLOGY 1998; 88: 7–17
Mangano DT, Layug EL, Wallace A, Tateo I: Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. N Engl J Med 1996; 335: 1713–20
Eagle KA, Froehlich JB: Reducing cardiovascular risk in-patients undergoing noncardiac surgery. N Engl J Med 1996; 335: 1761–3
Communal C, Singh K, Pimentel DR, Colucci WS: Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the beta-adrenergic pathway. Circulation 1998; 98: 1329–34
Shizukuda Y, Buttrick PM, Geenen DL, Borczuk AC, Kitsis RN, Sonnenblick EH: Beta-adrenergic stimulation causes cardiocyte apoptosis: Influence of tachycardia and hypertrophy. Am J Physiol 1998; 275: H961–8
Johansen JW, Schnider G, Windsor A, Sebel PS: Esmolol potentiates reduction of minimum alveolar isoflurane concentration by alfentanil. Anesth Analg 1998; 87: 671–6
Davidson EM, Szmuk P, Chelley J, Doursout MF: Esmolol reduces nociceptive behavior in the rat formalin test (abstract). A NESTHESIOLOGY 1997; 87: A731
Warltier DC: Beta-adrenergic-blocking drugs: Incredibly useful, incredibly underutilized (editorial). A NESTHESIOLOGY 1998; 88: 2–5
Ponten J, Biber B, Henriksson BA, Hjalmarson A, Jonsteg C, Lundberg D:β-Receptor blockade and neurolept analgesia: Withdrawal vs continuation of long-term therapy in gall bladder and carotid artery surgery. Acta Anaesth Scand 1982; 26: 576–8.
Reich DL, Osinski TK, Bodian C, Krol M, Sarier K, Roth R, Konstadt SN: An algorithm for assessing intraoperative mean arterial pressure. A NESTHESIOLOGY 1997; 87: 156–61
Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, Schwam EM, Siegel JL: Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: Study with intravenous midazolam. J Clin Psychopharmacol 1990; 10: 244–51
Mangano DT, Browner WS, Hollenberg M, London MJ, Tubau JF, Tateo IM: Association of perioperative myocardial ischemia with cardiac morbidity and mortality in men undergoing noncardiac surgery. N Engl J Med 1990; 323: 1781–8
Arnalich F, Sanchez JF, Martinez M, Jimenez M, Lopez J, Vazquez JJ, Hernanz A: Changes in plasma concentrations of vasoactive neuropeptides in patients with sepsis and septic shock. Life Sci 1994; 56: 75–81
Morris MJ, Russell AE, Kapoor V, Cain MD, Elliott JM, West MJ, Wing LM, Chalmers JP: Increases in plasma neuropeptide Y concentrations during sympathetic activation in man. J Auton Nerv Syst 1986; 17: 143–9
Chernow B, Alexander HR, Smallridge RC, Thompson WR, Cook D, Beardsley D, Fink MP, Lake CR, Fletcher JR: Hormonal responses to graded surgical stress. Arch Int Med 1987; 147: 1273–8
Parker SD, Breslow MJ, Frank SM, Rosenfeld BA, Norris EJ, Christopherson R, Rock P, Gottlieb SO, Raff H, Perler BA: Catecholamine and cortisol responses to lower extremity revascularization: Correlation with outcome variables. Crit Care Med 1995; 23: 1954–61
Roizen MF, Horrigan RW, Frazer BM: Anesthetic doses blocking adrenergic (stress) and cardiovascular responses to incision: MAC BAR. A NESTHESIOLOGY 1981; 54: 390–8
Johansen JW, Flaishon R, Sebel PS: Esmolol reduces anesthetic requirement for skin incision during propofol/nitrous oxide/morphine anesthesia. A NESTHESIOLOGY 1997; 86: 364–71
Stanley TH, De Lange S, Boscoe MJ, de Bruijn N: The influence of chronic preoperative propranolol therapy on cardiovascular dynamics and narcotic requirements during operation in patients with coronary artery disease. Can Anaesth Soc J 1982; 29: 319–24
Murmann W, Almirante L, Saccani-Guelfi M: Central nervous system effects of four beta-adrenergic receptor blocking agents. J Pharm Pharmacol 1966; 18: 317–8
Granville-Grossman KL, Turner P: The effect of propranolol on anxiety. Lancet 1966; 1: 788–90
Neil-Dwyer G, Bartlett J, McAinsh J, Cruickshank JM: Beta-adrenoceptor blockers and the blood-brain barrier. Br J Clin Pharmacol 1981; 11: 549–53
Selye H: The evolution of the stress concept: Stress and cardiovascular disease. Am J Cardiol 1970; 26: 289–99
Breslow MJ, Jordan DA, Christopherson R, Rosenfeld B, Miller CF, Hanley DF, Beattie C, Traystman RJ, Rogers MC: Epidural morphine decreases postoperative hypertension by attenuating sympathetic nervous system hyperactivity. JAMA 1989; 261: 3577–81
Rutberg H, Hakanson E, Anderberg B, Jorfeldt L, Martensson J, Schildt B: Effects of the extradural administration of morphine, or bupivacaine, on the endocrine response to upper abdominal surgery. Br J Anaesth 1984; 56: 233–8
Flacke JW, Bloor BC, Flacke WE, Wong D, Dazza S, Stead SW, Laks H: Reduced narcotic requirement by clonidine with improved hemodynamic and adrenergic stability in patients undergoing coronary bypass surgery. A NESTHESIOLOGY 1987; 67: 11–9
Engelman E, Lipszyc M, Gilbart E, Van der Linden P, Bellens B, Van Romphey A, de Rood M: Effects of clonidine on anesthetic drug requirements and hemodynamic response during aortic surgery. A NESTHESIOLOGY 1989; 71: 178–87
Rampil IJ, Mason P, Singh H: Anesthetic potency (MAC) is independent of forebrain structures in the rat. A NESTHESIOLOGY 1993; 78: 707–12
Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, Finn SE, Mascia MP, Valenzuela CF, Hanson KK, Greenblatt EP, Harris RA, Harrison NL: Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors. Nature 1997; 389: 385–9
Voerman HJ, Strack van Schijndel RJ, Groeneveld AB, de Boer H, Nauta JP, Thijs LG: Pulsatile hormone secretion during severe sepsis: accuracy of different blood sampling regimens. Metabolism 1992; 41: 934–40
Lake CR, Ziegler MG, Kopin IJ: Use of plasma norepinephrine for evaluation of sympathetic neuronal function in man. Life Sci 1976; 18: 1315–25
Zukowska-Grojec Z: Neuropeptide Y: A novel sympathetic stress hormone and more. Ann N Y Acad Sci 1995; 771: 219–33
Tanaka E, Mori H, Chujo M, Yamakawa A, Mohammed MU, Shinozaki Y, Tobita K, Sekka T, Ito K, Nakazawa H: Coronary vasoconstrictive effects of neuropeptide Y and their modulation by the ATP-sensitive potassium channel in anesthetized dogs. J Am Coll Cardiol 1997; 29: 1380–9
Hulting J, Sollevi A, Ullman B, Franco-Cereceda A, Lundberg JM: Plasma neuropeptide Y on admission to a coronary care unit: Raised levels in patients with left heart failure. Cardiovasc Res 1990; 24: 102–8
Clarke JG, Davies GJ, Kerwin R, Hackett D, Larkin S, Dawbarn D, Lee Y, Bloom SR, Yacoub M, Maseri A: Coronary artery infusion of neuropeptide Y in patients with angina pectoris. Lancet 1987; 1: 1057–9
McSPI—Europe Research Group: Perioperative sympatholysis: Beneficial effects of the alpha 2-adrenoceptor agonist mivazerol on hemodynamic stability and myocardial ischemia. A NESTHESIOLOGY 1997; 86: 346–63
Cook JR, Bigger JT Jr, Kleiger RE, Steinmann RC, Rolnitzky LM: Effects of atenolol and diltiazem on heart period variability in normal persons. J Am Coll Cardiol 1991; 17: 480–4
Glass PS, Bloom M, Kearse L, Rosow C, Sebel P, Manberg P: Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane and alfentanil in healthy volunteers. A NESTHESIOLOGY 1997; 86: 836–47
Chortkoff BS, Bennett HL, Eger EI II: Subanesthetic concentrations of isoflurane suppress learning as defined by the category-example task. A NESTHESIOLOGY 1993; 79: 16–22
Ghoneim MM, Block RI: Learning and memory during general anesthesia: An update. A NESTHESIOLOGY 1997; 87: 387–410
Jakobsen CJ, Blom L: Effect of pre-operative metoprolol on cardiovascular and catecholamine response and bleeding during hysterectomy. Eur J Anaesthesiol 1992; 9: 209–15
Antman EM, Tanasijevic MJ, Thompson B, Schactman M, McCabe CH, Cannon CP, Fischer GA, Fung AY, Thompson C, Wybenga D, Braunwald E: Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 1996; 335: 1342–9
Kost GJ, Kirk JD, Omand K: A strategy for the use of cardiac injury makers (troponin I and T, creatine kinase-mb mass and isoforms, and myoglobin) in the diagnosis of acute myocardial infarction. Arch Pathol Lab Med 1998; 122: 245–51
Missov E, Calzolari C, Pau B: Circulating cardiac troponin I in severe congestive heart failure. Circulation 1997; 96: 2953–8
Liao J, Keiser JA, Scales WE, Kunkel SL, Kluger MJ: Role of epinephrine in TNF and IL-6 production from isolated perfused rat liver. Am J Physiol. 1995; 268: R896–901
Fig. 1. Schematic diagram of intravenous atenolol administration for each group. 
Fig. 1. Schematic diagram of intravenous atenolol administration for each group. 
Fig. 1. Schematic diagram of intravenous atenolol administration for each group. 
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Fig. 2. Heart rate (HR, mean ± SD) at the various time points for each anesthetic group. Repeated-measures analysis of variance (  P  = 0.035) indicated that the groups differed in HR over time. Differences between groups were analyzed using the Bonferroni–Dunn  post hoc  test (with  P  < 0.017 significant): group I  versus  II,  P  = 0.014; group I  versus  III,  P  = 0.001; group II  versus  III,  P  = 0.80. Paired  t  tests with Bonferroni correction for multiple comparisons (with  P  < 0.01 significant) were used to compare HR at each time point with the respective preoperative baseline value for each group. *Significantly increased compared to baseline values;**Significantly decreased compared to baseline values. 
Fig. 2. Heart rate (HR, mean ± SD) at the various time points for each anesthetic group. Repeated-measures analysis of variance (  P  = 0.035) indicated that the groups differed in HR over time. Differences between groups were analyzed using the Bonferroni–Dunn  post hoc  test (with  P  < 0.017 significant): group I  versus  II,  P  = 0.014; group I  versus  III,  P  = 0.001; group II  versus  III,  P  = 0.80. Paired  t  tests with Bonferroni correction for multiple comparisons (with  P  < 0.01 significant) were used to compare HR at each time point with the respective preoperative baseline value for each group. *Significantly increased compared to baseline values;**Significantly decreased compared to baseline values. 
Fig. 2. Heart rate (HR, mean ± SD) at the various time points for each anesthetic group. Repeated-measures analysis of variance (  P  = 0.035) indicated that the groups differed in HR over time. Differences between groups were analyzed using the Bonferroni–Dunn  post hoc  test (with  P  < 0.017 significant): group I  versus  II,  P  = 0.014; group I  versus  III,  P  = 0.001; group II  versus  III,  P  = 0.80. Paired  t  tests with Bonferroni correction for multiple comparisons (with  P  < 0.01 significant) were used to compare HR at each time point with the respective preoperative baseline value for each group. *Significantly increased compared to baseline values;**Significantly decreased compared to baseline values. 
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Fig. 3. Systolic rate-pressure product (RPP, mean ± SD) values at various time points for each anesthetic group. Repeated-measures analysis of variance (  P  = 0.02) indicated that the groups differed in RPP over time. Differences between groups were analyzed using the Bonferroni–Dunn  post hoc  test (  P  < 0.017 is significant): group I  versus  II,  P  = 0.016; group I  versus  III,  P  < 0.0001; group II  versus  III,  P  = 0.10. Paired  t  tests with Bonferroni correction for multiple comparisons (with  P  < 0.01 significant) were used to compare RPP at each time point with the respective preoperative baseline value for each group. *Significantly increased compared with baseline values. **Significantly decreased compared with baseline values. 
Fig. 3. Systolic rate-pressure product (RPP, mean ± SD) values at various time points for each anesthetic group. Repeated-measures analysis of variance (  P  = 0.02) indicated that the groups differed in RPP over time. Differences between groups were analyzed using the Bonferroni–Dunn  post hoc  test (  P  < 0.017 is significant): group I  versus  II,  P  = 0.016; group I  versus  III,  P  < 0.0001; group II  versus  III,  P  = 0.10. Paired  t  tests with Bonferroni correction for multiple comparisons (with  P  < 0.01 significant) were used to compare RPP at each time point with the respective preoperative baseline value for each group. *Significantly increased compared with baseline values. **Significantly decreased compared with baseline values. 
Fig. 3. Systolic rate-pressure product (RPP, mean ± SD) values at various time points for each anesthetic group. Repeated-measures analysis of variance (  P  = 0.02) indicated that the groups differed in RPP over time. Differences between groups were analyzed using the Bonferroni–Dunn  post hoc  test (  P  < 0.017 is significant): group I  versus  II,  P  = 0.016; group I  versus  III,  P  < 0.0001; group II  versus  III,  P  = 0.10. Paired  t  tests with Bonferroni correction for multiple comparisons (with  P  < 0.01 significant) were used to compare RPP at each time point with the respective preoperative baseline value for each group. *Significantly increased compared with baseline values. **Significantly decreased compared with baseline values. 
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Fig. 4. Cardiac troponin I (cTnI) levels for patients in each anesthetic group. Peak levels of cTnI (only the highest level for each patient is presented) measured during the perioperative period are presented. Values are presented as nanograms/milliliter serum. Values above 0.4 ng/ml (  lower  ) are indicative of micronecrosis. Values above 1.5 ng/ml (  upper  ) are indicative of myocardial infarction. 
Fig. 4. Cardiac troponin I (cTnI) levels for patients in each anesthetic group. Peak levels of cTnI (only the highest level for each patient is presented) measured during the perioperative period are presented. Values are presented as nanograms/milliliter serum. Values above 0.4 ng/ml (  lower  ) are indicative of micronecrosis. Values above 1.5 ng/ml (  upper  ) are indicative of myocardial infarction. 
Fig. 4. Cardiac troponin I (cTnI) levels for patients in each anesthetic group. Peak levels of cTnI (only the highest level for each patient is presented) measured during the perioperative period are presented. Values are presented as nanograms/milliliter serum. Values above 0.4 ng/ml (  lower  ) are indicative of micronecrosis. Values above 1.5 ng/ml (  upper  ) are indicative of myocardial infarction. 
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Table 1. Patient Characteristics 
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Table 1. Patient Characteristics 
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Table 2. Perioperative Neuroendocrine Stress Response 
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Table 2. Perioperative Neuroendocrine Stress Response 
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Table 3. Intraoperative Hemodynamic Responses: Percent of Total Anesthesia Time 
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Table 3. Intraoperative Hemodynamic Responses: Percent of Total Anesthesia Time 
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Table 4. Intraoperatively Administered Medication 
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Table 4. Intraoperatively Administered Medication 
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Table 5. Incidence of Perioperative Hemodynamic Abnormalities 
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Table 5. Incidence of Perioperative Hemodynamic Abnormalities 
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Table 6. Recovery Data 
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Table 6. Recovery Data 
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