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J Thorac Cardiovasc Surg 2007;134:460-464
© 2007 The American Association for Thoracic Surgery

Surgery for Acquired Cardiovascular Disease

Impact of high thoracic epidural anesthesia on incidence of perioperative atrial fibrillation in off-pump coronary bypass grafting: A prospective randomized study

Farhad Bakhtiary, MDa,*, Panagiotis Therapidis, MDa, Omer Dzemali, MDa, Koray Ak, MDa, Hanns Ackermann, MD, PhDc, Dirk Meininger, MD, PhDb, Paul Kessler, MD, PhDd, Peter Kleine, MD, PhDa, Anton Moritz, MD, PhDa, Tayfun Aybek, MD, PhDa, Selami Dogan, MDa

a Department of Thoracic & Cardiovascular Surgery, Johann Wolfgang Goethe University Hospital, Frankfurt/Main, Germany
b Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Johann Wolfgang Goethe University Hospital, Frankfurt/Main, Germany
c Department of Biomedical Statistics, Johann Wolfgang Goethe University Hospital, Frankfurt/Main, Germany
d Department of Anesthesiology and Intensive Care Medicine, Friedrichsheim Foundation, Frankfurt/Main, Germany.

Received for publication February 22, 2007; revisions received March 15, 2007; accepted for publication March 29, 2007.

* Address for reprints: Farhad Bakhtiary, MD, Department of Thoracic & Cardiovascular Surgery, Johann Wolfgang Geothe University Hospital, Theodor-Stern-Kai 7, 60596 Frankfurt/Main, Germany. (Email: farhad{at}bakhtiary.de).


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Study Limitations
 References
 
Objective: Atrial fibrillation is one of the most common complications in patients undergoing coronary artery bypass grafting. The goal of this study was to investigate the impact of high thoracic epidural anesthesia on reduction of perioperative arrhythmia in patients undergoing off-pump coronary artery bypass grafting.

Methods: We prospectively randomized 132 patients undergoing elective off-pump coronary bypass grafting using either general anesthesia (GA) (n = 66) or combined general and high thoracic epidural anesthesia (GA+TEA) (n = 66). Incidence of perioperative arrhythmias such as atrial fibrillation, serum epinephrine levels, heart rate variability, and hemodynamic parameters were compared between groups.

Results: The incidence of perioperative dysarrhythmias was significantly lower (P < .01) in the GA+TEA group (3%) than in the GA group (23.7%). Intraoperative sinus bradycardia occurred in 91% of the patients in the GA+TEA group versus 5.3% in the GA group. After induction of anesthesia, the mean systolic arterial pressure decreased significantly from 128 ± 5 to 92 ± 4 mm Hg and the heart rate from 74 ± 9 to 52 ± 8 beats · min–1 in the GA+TEA group, whereas in the GA group no significant hemodynamic changes were observed (P < .001). Serum epinephrine levels were significantly lower in the GA+TEA group (69 ± 11 to 35 ± 7 ng/dL) than in the GA group (72 ± 9 to 70 ± 9 ng/dL).

Conclusions: In our study cohort, high thoracic epidural anesthesia in combination with general anesthesia reduced significantly the incidence of perioperative arrhythmias such as atrial fibrillation. Furthermore, we observed a significant reduction of epinephrine serum levels in this patient group. The results of this study support a combination of general anesthesia with thoracic epidural anesthesia as a multidisciplinary approach, which may lead to a better patient outcome, improvement of early analgesia, and reduction of perioperative complications in off-pump coronary artery bypass procedures. The potential risks of thoracic epidural anesthesia during off-pump coronary artery bypass procedures should not be underestimated.

Abbreviations and Acronyms AF = atrial fibrillation; CABG = coronary artery bypass grafting; ECG = electrocardiogram; GA = general anesthesia; OPCAB = off-pump coronary artery bypass grafting; TEA = high thoracic epidural anesthesia


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Study Limitations
 References
 
Perioperative arrhythmias such as atrial fibrillation (AF) are the most common complications in patients undergoing off-pump coronary bypass grafting (OPCAB), with a reported prevalence of 5% to 29%.1-5Go The etiology of AF is not widely known and has been related to many risk factors.6-8Go Activation of the autonomic nervous system seems to enhance or trigger the initiation and perpetuation of AF.9Go Recent studies have also reported that prophylactic administration of ß-blocker therapy may reduce the incidence of postoperative AF and reduce the length of hospital stay after cardiac surgery.10,11Go

General anesthesia (GA) is the most commonly used anesthetic technique and is considered the "gold standard" for coronary artery bypass grafting (CABG) performed either on pump or off pump.12Go Within the past few years, however, high thoracic epidural anesthesia (TEA) as an adjunct to GA has become more prevalent and has been shown to be potentially beneficial in patients with coronary artery disease.13Go Potential advantages of TEA include thoracic sympathicolysis with subsequent improvement of coronary perfusion, decreased heart rate, the latter being particularly important in OPCAB, decreased endogenous stress response, and a reduced risk for preoperative myocardial ischemia. Furthermore, improved postoperative pulmonary and gastrointestinal function with concomitant decreases in morbidity and mortality has been reported.12Go Additionally, postoperative pain management is facilitated by continuous epidural application of analgesics. Such effective pain management improves postoperative mobilization and recovery.12Go The risks associated with TEA are infections and hematoma formation with subsequent adverse neurologic sequelae.13Go The aim of the present trial was to verify in a prospective randomized design whether the use of TEA leads to a reduction of perioperative arrhythmias in patients undergoing OPCAB.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Study Limitations
 References
 
After approval by the institutional ethics board and with written informed consent, a total of 132 patients with symptomatic coronary artery disease were prospective enrolled in this study. All patients underwent elective OPCAB surgery and were randomized to receive either GA or combined GA+TEA. Patients with a history of atrial arrhythmias, those undergoing emergency operations, and patients requiring intraoperative inotropic support were excluded from this study. The incidence of perioperative arrhythmias such as AF, serum epinephrine levels, heart rate variability, and hemodynamic parameters were compared between the two groups. The hypothesis of the study was to determine whether the impact of the TEA in reduction of perioperative dysarrhythmias could be demonstrated in patients undergoing OPCAB.

Surgical Technique
The chest was opened either by complete sternotomy for double or triple CABG or by partial lower ministernotomy for single CABG. A small pediatric thorax retractor (Aeskulap, Tüttlingen, Germany) was used for exposition and harvesting of the left internal thoracic artery. Intravenous heparin was given in a standard dose of 150 IU/kg after thoracic artery dissection. A 75% reversal of heparin was performed with intravenous protamine at thorax closure. The activated coagulation time was measured to ensure appropriate heparin effect and reversal. An activated clotting time around 250 seconds during the operation was attained. After creating a pericardial cradle, the surgeon exposed the target vessels and used Octopus 4 (Medtronic Inc, Minneapolis, Minn) for stabilization of the target vessels. Anastomoses were performed in standard beating heart bypass technique using proximal control of the target coronary artery with a vessel loop and a blower mister to clear the anastomotic site.

GA and TEA
Antiplatelet therapy was stopped 5 days before the operation in all cases. In the TEA group, a multiport epidural catheter (Perifix Soft 505; B. Braun Melsungen AG, Melsungen, Germany) was inserted at the T1/2 or T2/3 intercostal space on the day before the operation. On the day of the operation, all patients were premedicated with oral midazolam, 7.5 mg.

On arrival of the patient in the preoperative holding area, intravenous access and direct blood pressure monitoring by catheterization of the radial artery were established regardless of the anesthetic technique used. In patients receiving TEA, a continuous epidural infusion with ropivacaine 0.16% and sufentanil 1 µg · mL–1 at an hourly rate of 2 to 5 mL was started after a bolus dose of 6 mL to provide intraoperative analgesia.

After induction of general anesthesia, a central venous line was inserted and correct placement confirmed by intra-atrial electrocardiographic (ECG) lead (Alphacard; B.Braun AG, Melsungen, Germany). Additional monitoring consisted of continuous automated ST-segment analysis at J + 60 ms for leads I, II, and V5 (Hellige Marquette Solar 8000 Patient Monitor; Marquette Medical Systems, Milwaukee, Wis). An ST-segment alteration of 1 mm or more (0.1 mV) persisting more than 60 seconds was considered a significant alteration from baseline. Oxygenation and ventilation were continuously monitored by pulse oximetry and capnography. Body temperature was maintained in all patients with a warming blanket (Bair Hugger model 505; Augustine Medical, Inc, Eden Prairie, Minn) and continuously monitored with a rectal temperature probe.

Anesthesia was induced with propofol (1.5 mg · kg–1) and remifentanil (1 µg · kg–1) administered over 120 seconds. After loss of eyelash reflex, 0.1 mg · kg–1 of cisatracurium was administered to facilitate tracheal intubation. Anesthesia was maintained with continuous infusion of propofol (50-100 µg · kg–1 · min–1) and remifentanil (0.1-0.3 µg · kg–1 · min–1). Positive-pressure ventilation with oxygen 50% in air was used. Tidal volume (8-10 mL · kg–1) and respiratory rate (10-12 min–1) were adjusted according to the end-tidal pressure of carbon dioxide to achieve normal ventilation (end-tidal pressure of carbon dioxide 35-40 mm Hg). Patients undergoing GA without TEA received intravenous metamizole (Novalgin; Aventis Pharma, Bad Soden, Germany), a peripheral analgesic derived from pyrazolone acid, 15 mg · kg–1, before skin incision. Intravenous piritramide, a µ-receptor agonist with a potency of 0.7 compared with morphine, 0.1 mg · kg–1, was administered after completion of coronary anastomosis and repeated during wound closure. The thoracic epidural catheter was used for not only intraoperative but also postoperative pain management for 3 days. Depending on pain perception, patients received additional analgesics and sedative hypnotic agents, as routinely used in our department.

Monitoring included arterial and central venous blood pressure measurement, ECG (leads II, aVF, and V5), pulse oximetry, and end-tidal carbon dioxide (Hellige Marquette Solar 8000 Patient Monitor, Marquette Medical Systems, Milwaukee, WI). Any newly developed sustained episode of cardiac arrhythmia was detected and printed with a continuous monitoring ECG system (Hellige Marquette Solar 8000 Patient Monitor; Marquette Medical Systems, Milwaukee, Wis) with automatic arrhythmia analysis for 48 hours. Thereafter, twice daily 12-lead ECGs were performed until hospital discharge and in each case with clinical symptoms caused by rhythm disturbance. In the case of documented arrhythmia, continuous ECG monitoring was restarted. AF was defined an episode of atrial fibrillation or flutter lasting for more than 30 seconds.

Statistical Analysis
Data were compiled and analyzed with Microsoft Excel (Redmond, Wash) and StatView (SAS Institute, Inc, Cary, NC). The baseline characteristics and hospital outcomes for both groups were compared by {chi}2 contingency or the Fisher exact test for categorical data and the Mann–Whitney U test for continuous variables. Results are reported as the mean ± standard deviation in text and tables.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Study Limitations
 References
 
There were no significant differences in preoperative clinical characteristics including gender, sinus rhythm, left ventricular ejection fraction, preoperative antiarrhythmic medication, and cardiovascular risk factors between the two groups (Table 1).


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  		TABLE 1 Patient characteristics
 
Table 2 demonstrates operative data, incidence of arrhythmias, and the time of onset of perioperative AF. There was no significant difference between the operation time, blood loss, ventilation time, and numbers of distal anastomoses. No relevant TEA-related complications such as puncture site infection, epidural hematoma, nerve injury, neurologic deficits, accidental dura puncture, or lower-limb motor block were observed. However, women, especially, were more prone to nausea and vomiting in the GA+TEA group. There was no in-hospital mortality in either group. The incidence of perioperative AF was significantly lower (P < .01) in the GA+TEA group (3%) than in the GA group (23.7%). Time of onset of AF did not differ between the two groups. Patients with AF lasting more than 10 minutes or those requiring medical attention because of hemodynamic instability were treated with ß-blockers (metoprolol 100 mg/d), amiodarone (5 mg/kg over 60 minutes followed by infusion of 1200 mg/d), or digitoxin and electrical cardioversion (in case of hemodynamic instability or failure of pharmacologic treatment). Anticoagulation with heparin was started routinely. Intraoperative sinus bradycardia occurred in 91% of the patients in the GA+TEA group versus 5.3% in the GA group. After induction of anesthesia, the mean systolic arterial pressure decreased significantly from 128 ± 5 to 92 ± 4 mm Hg and heart rate from 74 ± 9 to 52 ± 8 beats · min–1 in the GA+TEA group, whereas in the GA group no significant hemodynamic changes were observed (Figure 1; P < .001). We observed one case of ventricular fibrillation in each group.


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  		TABLE 2 Perioperative data
 

Figure 1
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  		Figure 1. Intraoperative heart rate monitoring. A, Before induction of anesthesia; B, sternotomy; C, before anastomosis; D, after anastomosis; E, sternal closure. GA, General anesthesia; TEA, high thoracic epidural anesthesia.

 
Serum epinephrine levels were significantly lower in group GA+TEA (69 ± 11 to 35 ± 7 ng · dL–1) than in in group GA (72 ± 9 to 70 ± 9 ng · dL–1; P < .001) (Figure 2).


Figure 2
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  		Figure 2. Serum epinephrine levels. A, Before induction of anesthesia; B, sternotomy; C, before anastomosis; D, after anastomosis; E, sternal closure; F, 1 hour postoperatively. GA, General anesthesia; TEA, high thoracic epidural anesthesia.

 
The incidence of nonsustained ventricular extrasystole was significantly lower (P < .01) in the GA+TEA group. There was no case of myocardial infraction in either group. Length of hospital stay did not differ between the two groups.


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Study Limitations
 References
 
Despite continuous development in minimizing surgical, anesthesiologic, or cardiopulmonary bypass trauma in CABG procedures, perioperative morbidity and clinical complications are still significant.14Go AF remains one of the most frequent complications in patients undergoing CABG, and it may lead to increased morbidity and length of hospital stay. Imbalance in the autonomic nervous system may cause changes in sinus node function and electrical atrial conduction as well as refractoriness previously shown to be related to the propensity for AF. Surgical trauma associated with increased sympathetic stimulation may also be a trigger for the onset of AF.7,8Go

The current prospective randomized study was designed to investigate the impact of the TEA on the incidence of perioperative arrhythmias with major attention to AF. The perioperative use of GA in combination with TEA in our study cohort led to stress-response attenuation and intense perioperative analgesia. We demonstrated that patients in the GA+TEA group had a significantly lower incidence of AF and ventricular extrasystoles. In the GA+TEA group, serum levels of epinephrine were significantly lower, which may support the hypothesis in regard to preventing the imbalance of sympathetic activity.

TEA seems to attenuate the secretion of epinephrine from the adrenal gland, which may have a positive effect on the balance within the autonomous nervous system. The effect of TEA on heart rate and blood pressure is also in accordance with this observation. Inhibition of sympathetic activity during the perioperative period may reduce postoperative myocardial ischemia.15Go This effect is most related to the balance of myocardial oxygen demand and supply. Most episodes of myocardial ischemia occur in the absence of major hemodynamic changes.16,17Go Thus, the use of TEA in patients with significant coronary artery disease may improve oxygen supply, so long as blood pressure is maintained in a relatively normal range. These effects also facilitate beating heart surgery in regard to suturing conditions with a lower heart rate and blood pressure.

Our data support the hypothesis that perioperative imbalance of the autonomic nervous system may lead to a higher incidence of AF. We believe the reduced incidence of AF in our study cohort was related to sympathicolytic properties of TEA.

Furthermore, perioperative myocardial ischemia may be aggravated by sympathetic nerve activation, which disturbs the balance between coronary blood flow and myocardial oxygen demand.16,17Go

Recent studies have also shown that ropivacaine has a substantial anti-inflammatory effect. Blumenthal and associates18Go could demonstrate that ropivacaine has strong anti-inflammatory effects on neutrophils and endothelial cells both in vitro and in vivo.

In our study we could not measure any inflammatory parameters between the groups. However, we speculate that TEA may also decrease the systemic inflammatory response and consequently the development of AF.


   Study Limitations
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Study Limitations
References
 
The study investigates a small number of patients. All patients were preselected by an anesthesiologist for eligibility to receive an epidural catheter before randomization. Patients with contraindications for TEA were excluded from the study. We did not measure any inflammatory parameters. Overall, longer follow-up periods and also a larger number of patients are necessary to corroborate our findings.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Study Limitations
 References
 

  1. Aranki SF, Shaw DP, Adams DH, Rizzo RJ, Couper GS, VanderVliet M, et al. Predictors of atrial fibrillation after coronary artery surgery. Current trends and impact on hospital resources. Circulation 1996;94:390-397.[Abstract/Free Full Text]
  2. MultiCenter Study of Perioperative Ischemia Research GroupMathew JP, Parks R, Savino JS, Friedman AS, Koch C, Mangano DT, et al. Atrial fibrillation following coronary artery bypass graft surgery: predictors, outcomes, and resource utilization. JAMA 1996;276:300-306.[Abstract]
  3. Mueller XM, Tevaearai HT, Ruchat P, Stumpe F, von Segesser LK. Did the introduction of a minimally invasive technique change the incidence of atrial fibrillation after single internal thoracic artery–left anterior descending artery grafting?. J Thorac Cardiovasc Surg 2001;121:683-688.[Abstract/Free Full Text]
  4. Cohn WE, Sirois CA, Johnson RG. Atrial fibrillation after minimally invasive coronary artery bypass grafting: a retrospective, matched study. J Thorac Cardiovasc Surg 1999;117:298-301.[Abstract/Free Full Text]
  5. Creswell LL, Schuessler RB, Rosenbloom M, Cox JL. Hazards of postoperative atrial arrhythmias. Ann Thorac Surg 1993;56:539-549.[Abstract]
  6. Stamou SC, Dangas G, Hill PC, Pfister AJ, Dullum MK, Boyce SW, et al. Atrial fibrillation after beating heart surgery. Am J Cardiol 2000;86:64-67.[Medline]
  7. Scherer M, Sirat AS, Aybek T, Martens S, Kessler P, Moritz A. Thoracic epidural anesthesia does not influence the incidence of postoperative atrial fibrillation after beating heart surgery. Thorac Cardiovasc Surg 2003;51:8-10.[Medline]
  8. Siebert J, Anisimowicz L, Lango R, Rogowski J, Pawlaczyk R, Brzezinski M, et al. Atrial fibrillation after coronary artery bypass grafting: does the type of procedure influence the early postoperative incidence?. Eur J Cardiothorac Surg 2001;19:455-459.[Abstract/Free Full Text]
  9. Kalman JM, Munawar M, Howes LG, Louis WJ, Buxton BF, Gutteridge G, et al. Atrial fibrillation after coronary artery bypass grafting is associated with sympathetic activation. Ann Thorac Surg 1995;60:1709-1715.[Abstract/Free Full Text]
  10. Halonen J, Hakala T, Auvinen T, Karjalainen J, Turpeinen A, Uusaro A, et al. Intravenous administration of metoprolol is more effective than oral administration in the prevention of atrial fibrillation after cardiac surgery. Circulation 2006;114(1 Suppl 1):I1-I4.[Medline]
  11. Connolly SJ, Cybulsky I, Lamy A, Roberts RS, O’brien B, Carroll S, et al. Beta-Blocker Length Of Stay (BLOS) study. Double-blind, placebo-controlled, randomized trial of prophylactic metoprolol for reduction of hospital length of stay after heart surgery: the beta-Blocker Length Of Stay (BLOS) study. Am Heart J 2003;145:226-232.[Medline]
  12. Wattwil M, Sundberg A, Arvill A, Lennquist C. Circulatory changes during high thoracic epidural anaesthesia—influence of sympathetic block and of systemic effect of the local anaesthetic. Acta Anaesthesiol Scand 1985;29:849-855.[Medline]
  13. Kessler P, Aybek T, Neidhart G, Dogan S, Lischke V, Bremerich DH, et al. Comparison of three anesthetic techniques for off-pump coronary artery bypass grafting: general anesthesia, combined general and high thoracic epidural anesthesia, or high thoracic epidural anesthesia alone. J Cardiothorac Vasc Anesth 2005;19:32-39.[Medline]
  14. Roques F, Nashef SA, Michel P, Gauducheau E, de Vincentiis C, Baudet E, et al. Risk factors and outcome in European cardiac surgery: analysis of the EuroSCORE multinational database of 19,030 patients. Eur J Cardiothorac Surg 1999;15:816-823.[Abstract/Free Full Text]
  15. Slogoff S, Keats AS. Randomized trial of primary anesthetic agents on outcome of coronary artery bypass operations. Anesthesiology 1989;70:179-188.[Medline]
  16. Liu S, Carpenter RL, Neal JM. Epidural anesthesia and analgesia. Their role in postoperative outcome. Anesthesiology 1995;82:1474-1506.[Medline]
  17. Slogoff S, Keats AS. Myocardial ischemia revisited. Anesthesiology 2006;105:214-216.[Medline]
  18. Blumenthal S, Borgeat A, Pasch T, Reyes L, Booy C, Lambert M, et al. Ropivacaine decreases inflammation in experimental endotoxin-induced lung injury. Anesthesiology 2006;104:961-969.[Medline]



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 J. Thorac. Cardiovasc. Surg.Home page
J. G.T. Augoustides
Thoracic epidural anesthesia and atrial fibrillation after coronary bypass grafting.
J. Thorac. Cardiovasc. Surg., February 1, 2008; 135(2): 466 - 467.
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 J. Thorac. Cardiovasc. Surg.Home page
F. Bakhtiary, H. Ackermann, D. Meininger, P. Kleine, A. Moritz, and S. Dogan
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J. Thorac. Cardiovasc. Surg., February 1, 2008; 135(2): 467 - 467.
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