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Canadian Journal of Anesthesia 50:638-642 (2003)
© Canadian Anesthesiologists' Society, 2003
General Anesthesia

Atenolol may not modify anesthetic depth indicators in elderly patients – a second look at the data

[L’aténolol ne modifierait pas les indicateurs de la profondeur de l’anesthésie chez les patients âgés - un réexamen des données]

Michael Zaugg, MD DEAA*, Thomas Tagliente, MD PhD{dagger}, Jeffrey H. Silverstein, MD{ddagger} and Eliana Lucchinetti, PhD§

* From the Institute of Anesthesiology,
§ University Hospital Zurich, Zurich, Switzerland;
{dagger} and the Department of Anesthesiology,
{ddagger} Mount Sinai School of Medicine, New York, USA.

Address correspondence to: Dr. Michael Zaugg, Institute of Anesthesiology, University Hospital, Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland. Phone: +41 1 255 11 11; Fax: +41 1 255 44 09; E-mail: michael.zaugg{at}ifa.usz.ch


   Abstract
TOP
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Purpose: Decreased cardiac chronotropic response in elderly patients along with concomitant ß-blockade may suppress the autonomic responsiveness to surgical stimulation and subsequently obscure episodes of "light anesthesia".

Methods: We analyzed post hoc computerized data from our previous study evaluating the effects of perioperative atenolol administration. Bispectral index (BIS) and the performance of routine anesthetic depth indicators were analyzed in 45 patients undergoing abdominal surgery: Group I (n = 12), isoflurane/fentanyl/nitrous oxide in oxygen anesthesia; Group II (n = 16), isoflurane/fentanyl/nitrous oxide in oxygen with 10 mg atenolol intravenously prior to anesthesia; Group III (n = 17), isoflurane/fentanyl/nitrous oxide in oxygen with a maximum end-tidal isoflurane concentration of 0.4 vol.% and incremental doses of atenolol (5 mg intravenously stepwise). In all groups, blood pressure (BP) was maintained within ± 20% of preoperatively defined baseline BP and heart rate (HR) between 50–80 beats•min-1. BP, HR, and end-tidal isoflurane were tested for their potential to predict BIS using a previously described statistical model (PK).

Results: Although Group III patients received on average 39.5% less isoflurane compared with Group I patients (P = 0.006), and Groups II and III patients received on average 21% less fentanyl compared with Group I patients (P <= 0.002), similar levels of intraoperative average BIS values (53–54) were obtained for all groups. Higher BIS values were reached at emergence in atenolol-treated patients. The performance of hemodynamic variables or end-tidal isoflurane to predict BIS was moderate even at critical intraoperative events, but unaffected by atenolol.

Conclusion: Atenolol reduces anesthetic requirements but may not modify anesthetic depth indicators in elderly patients.


   Introduction
TOP
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
WE recently reported the beneficial effects of ß-adrenergic blockade in elderly patients undergoing noncardiac surgery.1 In this study, atenolol was shown to confer the advantage of administering less anesthetics, which resulted in a faster recovery from anesthesia. To evaluate whether the use of atenolol promotes "light anesthesia"2 and to investigate whether the ability to judge the adequacy of anesthetic depth is diminished by atenolol, we analyzed post hoc computerized data from a subgroup of the study patients with comparable surgical stimulation (abdominal surgery). Specifically, we examined the effects of atenolol on the performance of the routinely used anesthetic depth indicators, i.e., heart rate (HR), blood pressure (BP), and end-tidal anesthetic gas concentrations to predict depth of anesthesia, as indicated by the bispectral index (BIS), using a previously described statistical model.3


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Patients and study protocol
From the 63 patients of the original study,1 the data from 45 patients, which fulfilled the following criteria were used for this analysis: 1) patients with abdominal surgery (comparable surgical stimuli); 2) patients with less than 1,000 mL of blood loss; 3) patients with less than 1% of missing electronically recorded data. In the original study, patients were randomly allocated to one of the following general anesthetic regimens: Group I: anesthetic technique without atenolol; Group II: anesthetic technique with preoperative administration of 10 mg atenolol intravenously 30 min prior to the start of anesthesia; Group III: anesthetic technique with intraoperative atenolol. In this group, maximum end-tidal isoflurane concentration was restricted to 0.4 vol.% and hemodynamics were controlled by stepwise (5 mg) iv administration of atenolol. Exclusion criteria were pretreatment with ß-blockers and any contraindication for the study drug atenolol.1 For all patients, anesthesia was induced with 100 to 250 µg fentanyl, propofol 1.7 mg•kg-1, and rocuronium 0.8 mg•kg-1. Anesthetic maintenance was performed with isoflurane, 66% nitrous oxide in oxygen, a continuous infusion of fentanyl 1 to 2 µg•kg-1•hr-1, and rocuronium according to the surgical requirements. For all groups, BP was maintained within 20% of preoperatively defined baseline mean arterial blood pressure (MAP) and HR between 50 to 80 beats•min-1.1

Intraoperative monitoring and data management
Data for HR, MAP, systolic arterial pressure (SAP), end-tidal isoflurane concentrations, and BIS [A-1050 monitoring system (software version 3.1) using Zipprep FpZ-F7 and FpZ-F8 electrodes, Aspect Medical Systems, Natick, MA, USA)] were automatically recorded from shortly before induction until eye opening.1 The raw electrocardiogram signals were band-pass filtered to 0.5 to 30 Hz. The smoothening time of BIS was set at 30 sec, and BIS was updated every five seconds. BIS data were blinded to the attending anesthesiologist. To eliminate artifacts, two-minute medians were computed for the recorded data. Absolute fractional changes between consecutive two-minute medians were calculated for all variables, as reported previously.1,4 The intraoperative period was defined from surgical incision until closure of the surgical wound. For this period, percent frequency distribution for intraoperative BIS values was calculated for the following ranges: < 40, 40–50, 50–60, 60–70, 70–80, > 80.

Assessing the performance of routine anesthetic depth indicators
Maximum BIS, HR, and SAP were determined for the predefined time points of intubation, incision, end of surgery, and extubation using the maximum values of data recorded ± four minutes within the critical events. The performance to predict BIS was calculated for HR, MAP, SAP, their absolute fractional changes between two consecutive two-minute epochs, and end-tidal isoflurane concentration using the previously described statistical model of prediction probability (PK).3 Calculations for PK were performed with a custom spreadsheet macro PKMACRO (Prof. W.D. Smith, Sate University, Sacramento, CA, USA) using Excel (Microsoft Corporation, Redmond, WA, USA). PK for the times of intubation, incision, end of surgery, and extubation were calculated by using three two-minute medians immediately before and after the defined critical events.

Statistical analysis
Data are expressed as mean ± SD, mean with 95% lower and upper confidence interval (for the prediction probability), or median (minimum, maximum), respectively, dependent upon the underlying data distribution. One-way analysis of variance was used to test for intergroup difference. Bonferroni/Dunn procedure was used to correct for multiple comparisons. P < 0.05 was considered statistically significant (StatView, Abacus Concepts, Inc., Berkeley, CA, USA).


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Of the 45 patients that met the selection criteria defined for the present subgroup analysis, 12 belonged to Group I, 16 to Group II, and 17 to Group III. There was no difference in patient characteristics between groups.1

Administered amount of anesthetics and atenolol and intraoperative hemodynamics
The amount of administered anesthetics was different for the three groups (Table IGo). Group III patients received on an average 39.5% less isoflurane compared with Group I patients (P = 0.006), and Groups II and III patients received on an average 21% less fentanyl compared with Group I patients (P <= 0.002). Hemodynamic variables were similarly well controlled in all groups.1


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  		TABLE I Administered drugs
 
Anesthetic depth and recovery
None of the patients experienced intraoperative awareness or recall, and the mean intraoperative BIS values were similar for all three groups (53–54).1 There was no intraoperative increase in BIS values at higher BIS ranges in atenolol-treated patients (Figure 1Go). Conversely, higher BIS values were observed in both atenolol-treated groups at the end of surgery and at extubation (Figure 2Go). This is in accordance with our previously reported faster recovery from anesthesia in both ß-blocker groups.1



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  		FIGURE 1 Percentages of intraoperative time for the indicated bispectral index (BIS) ranges are presented as box plots for the three anesthetic regimens (median, 25th and 75th percentile, 3rd and 97th, respectively). There were no intraoperative BIS values higher than 70 in any of the three anesthetic regimens. Also, no significant differences between groups were observed for higher intraoperative BIS ranges.

 


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  		FIGURE 2 Bispectral index (BIS) and hemodynamics at specific time points. There was no increase in peak BIS at intubation or incision in patients treated with atenolol. Conversely, higher BIS values were observed in both atenolol-treated groups (Groups I and II) at the end of surgery and at extubation. Heart rate and blood pressure were better controlled in both ß-blocker groups, particularly at the time of extubation. BISMAX = maximum bispectral index; HRMAX = maximum heart rate (beats•min-1); and SAPMAX = maximum systolic arterial pressure (mmHg) at the indicated time points.*Significantly different compared to Group I (control). Data are mean ± SD. 1 = Group I; 2 = Group II; 3 = Group III.

 
Performance of routine anesthetic depth indicators
Overall performance of all routine anesthetic depth indicators was in general poor, regardless of the anesthetic regimen or the presence or absence of ß-blockade (Table IIGo). The performance of the indicators measured at critical time points, i.e., at intubation, at incision, at the end of surgery, and at extubation was markedly higher, but still not satisfactory (ideally PK > 80 or PK < 20). In all study groups, end-tidal isoflurane concentrations could predict BIS best. Unexpectedly, HR as well as the change in HR could predict intraoperative BIS significantly better under higher doses of atenolol (Table IIGo).


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  		TABLE II Performance of routine anesthetic depth indicators to predict bispectral index
 

   Discussion
TOP
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
In this study, we evaluated the effect of perioperative atenolol on anesthetic depth as indicated by BIS in patients undergoing abdominal surgery.1 Atenolol significantly decreased anesthetic requirements, but did not appear to alter the level of hypnosis. This is consistent with previous studies where esmolol decreased anesthetic requirements for skin incision,5,6 and directly promoted electroencephalographic burst suppression during anesthesia.7 Conversely, a significantly faster recovery from anesthesia was observed in our ß-blocker-treated patients.1 Titration of anesthetics to HR and BP without ß-blockade may lead to prolonged recovery from anesthesia due to administration of higher doses of anesthetics (MAC-BAR > MAC-awake).8 Our post hoc analysis also evaluated the impact of ß-blockade on the performance of routine anesthetic depth indicators using the previously established model of prediction probability PK.3 The results of these analyses indicate that routinely used hemodynamic variables do not reliably predict BIS, regardless of the presence or absence of ß-blockade. Poor prediction of the hypnotic state by hemodynamic variables was recently reported by Struys et al.9 Interestingly, we observed a better performance of HR to predict BIS in the presence of higher doses of atenolol. Although end-tidal anesthetic concentration could predict BIS better than any hemodynamic variable, this correlation was weak, but unaffected by ß-blockade.

In summary, atenolol reduces anesthetic requirements but may not modify anesthetic depth indicators in elderly patients.


   Acknowledgments
 
The authors are indebted to Prof. W.D. Smith for providing the PKMACRO software used in this study.


   Footnotes
 
This study was supported by the Grant 3200-063417.00 of the Swiss National Science Foundation and a Grant of the Swiss Heart Foundation.

Revision received February 12, 2003. Accepted for publication September 24, 2002.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
1 Zaugg M, Tagliente T, Lucchinetti E, et al. Beneficial effects from ß-adrenergic blockade in elderly patients undergoing noncardiac surgery. Anesthesiology 1999; 91: 1674–86.[Medline]

2 Hameroff SR, Polson JS, Watt RC. Monitoring anesthetic depth. In: Blitt CD, Hines RL (Eds.). Monitoring in Anesthesia and Critical Care Medicine, 3rd ed. New York: Churchill Livingstone; 1995: 491–507.

3 Smith WD, Dutton RC, Smith NT. Measuring the performance of anesthetic depth indicators. Anesthesiology 1996; 84: 38–51.[Medline]

4 Reich DL, Osinski TK, Bodian C, et al. An algorithm for assessing intraoperative mean arterial pressure lability. Anesthesiology 1997; 87: 156–61.[Medline]

5 Johansen JW, Schneider G, Windsor AM, Sebel PS. Esmolol potentiates reduction of minimum alveolar isoflurane concentration by alfentanil. Anesth Analg 1998; 87: 671–6.[Abstract/Free Full Text]

6 Johansen JW, Flaishon R, Sebel PS. Esmolol reduces anesthetic requirement for skin incision during propofol/nitrous oxide/morphine anesthesia. Anesthesiology 1997; 86: 364–71.[Medline]

7 Johansen JW. Esmolol promotes electroencephalographic burst suppression during propofol/alfentanil anesthesia. Anesth Analg 2001; 93: 1526–31.[Abstract/Free Full Text]

8 Zaugg M, Schaub MC, Pasch T, Spahn DR. Modulation of ß-adrenergic receptor subtype activities in perioperative medicine: mechanisms and sites of action. Br J Anaesth 2002; 88: 101–23.[Abstract/Free Full Text]

9 Struys MM, Jensen EW, Smith WD, et al. Performance of the ARX-derived auditory evoked potential index as an indicator of anesthetic depth. A comparison with bispectral index and hemodynamic measures during propofol administration. Anesthesiology 2002; 96: 803–16.[Medline]




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