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J Saudi Heart Assoc
J Saudi Heart Assoc
Journal of the Saudi Heart Association
1016-7315
2212-5043
Saudi Heart Association

10.37616/2212-5043.1390
sha232-236
Original Article
Intraoperative Remifentanil Use Reduces Atrial Fibrillation After Coronary Artery Bypass Surgery
Imashuku Yasuhiko Supervision Visualization Writing - review & editing Writing - original draft Data curation Conceptualization Funding acquisition Formal analysis Investigation *
Hiraoka Susumu Writing - review & editing Data curation Investigation Funding acquisition
Inoue Motoi Data curation Investigation Funding acquisition
Mizuno Takayoshi Data curation Investigation Funding acquisition
Oyagi Misuzu Visualization Data curation Investigation Funding acquisition
Kitagawa Hirotoshi Supervision Writing - review & editing Writing - original draft Conceptualization Formal analysis
Department of Anesthesiology, Shiga University of Medical Science, 5202192, Otsu, Shiga, Japan
* Corresponding author at: Department of Anesthesiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga, 5202192, Japan. E-mail address: imashuku@belle.shiga-med.ac.jp (Y. Imashuku).
2024
17 8 2024
36 3 232236
10 5 2024
21 7 2024
22 7 2024
© 2024 Saudi Heart Association
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Objectives

Atrial fibrillation after coronary artery bypass grafting is a relatively well known complication that has been observed for a long time. Though the management and drugs in the perioperative period have changed, their impact on the generation of postoperative atrial fibrillation remains unclear. Therefore, we investigated various perioperative management methods and the occurrence of postoperative atrial fibrillation.

Methods

The patients underwent off-pump coronary artery bypass grafting between January 2010 and October 2019. The study was a retrospective observational study, and we investigated the incidence of atrial fibrillation during all 5 postoperative days. Patient factors included age, sex, height, and weight, preoperative factors included oral statin, HbA1c, left ventricular ejection fraction, and left atrial diameter; intraoperative factors included operation time, remifentanil use, beta-blocker use, magnesium-containing infusions use, in–out balance, and number of vascular anastomoses.

Results

Postoperative atrial fibrillation was recognized in 81 out of 276 cases. There were significant differences between the two groups in terms of age, left atrial diameter, and intraoperative remifentanil use. A logistic regression analysis presented the effects of age (OR 1.045, 95% CI 1.015–1.076, P < 0.01), preoperative left atrial diameter (OR 1.072, 95% CI 1.023–1.124, P < 0.01), and intraoperative remifentanil use (OR 0.492, 95% CI 0.284–0.852, P = 0.011) on postoperative atrial fibrillation.

Conclusions

Operative time did not affect postoperative atrial fibrillation. Age and left atrial diameter had previously been shown to affect postoperative atrial fibrillation, and our results were similar. This study showed that the use of remifentanil reduced the incidence of postoperative atrial fibrillation. On the other hand, no other factors were found to have an effect.

Coronary artery bypass surgery
Atrial fibrillation
Remifentanil
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pmc1. Introduction

A trial fibrillation is a type of arrhythmia that occurs frequently after cardiac surgery [1]. Postoperative atrial fibrillation has been reported to occur at a rate as high as 15–40% after coronary artery bypass surgery [2,3]. Studies suggest that the use of extracorporeal circulation does not affect the incidence of atrial fibrillation after coronary artery bypass surgery [4,5]. However, the situation is different from before, as surgery times are shorter and intraoperative remifentanil and magnesium-containing infusion products are used. On the other hand, how these changes may contribute to the incidence of postoperative atrial fibrillation remains unclear. To address this gap, we investigated the incidence of atrial fibrillation and the influence of perioperative management after off-pump coronary artery bypass graft surgery.

2. Methods

2.1. Patient selection

We enrolled patients who underwent standby off-pump coronary artery bypass graft surgery at our hospital between January 2010 and October 2019, were not on dialysis and did not have atrial fibrillation.

2.2. Method

This was a retrospective observational study. Patients had continuous electrocardiogram monitoring for five postoperative days, and all arrhythmias were documented in medical records. The incidence of atrial fibrillation during all five postoperative days was extracted from the medical records. Only the occurrence of atrial fibrillation was studied. (The duration of atrial fibrillation was not studied.) We also collected data regarding patient factors such as age, sex, height, and weight; preoperative factors such as statin use, HbA1C level, left ventricular ejection fraction, and left atrial diameter; and intraoperative factors such as remifentanil use, use of infusions containing magnesium, beta blocker use, IN–OUT balance, number of anastomotic sites, operative time, and anesthesia time.

2.3. Statistical analysis

To compare the two groups, we performed the unpaired t-test, Mann–Whitney’s U-test, and Chi-square for independence test after examining the normality of the data. Multivariate logistic regression analysis was used to examine associations. Statistical analysis was performed using Excel 2010 (Microsoft, USA) with the add-in software Statcel 2 (OMS, Japan) and IBM SPSS Statistics 29.0 (IBM, USA).

2.4. Ethical approval

The study was approved by the Ethics Committee of Shiga University of Medical Science [Approval No: R2019-275]. Since this study adopted a retrospective research method, informed consent was obtain in the form of opt-out on the web-site.

3. Results

Patient characteristics: A total of 276 patients were included after the inclusion/exclusion criteria were applied. Of them, 195 patients did not develop postoperative atrial fibrillation, whereas the remaining 81 patients developed postoperative atrial fibrillation (Fig. 1.)

Comparison of the two groups: A comparison of patient and operative characteristics between the patients with and without atrial fibrillation is presented in Table 1. There were significant differences between the two groups in terms of age, preoperative left atrial diameter, and intraoperative remifentanil use. There was no significant difference in any of the other factors (Table 1). A logistic regression analysis with postoperative atrial fibrillation as the dependent variable and each factor as the independent variable further demonstrated significant associations for age (odds ratio (OR): 1.045, 95% confidence interval (CI): 1.015–1.076, p < 0.01), preoperative left atrial diameter (OR: 1.072 95% CI: 1.023–1.124, p < 0.01), and remifentanil use (OR: 0.492, 95% CI: 0.284–0.852, p = 0.011) (Table 2).

4. Discussion

Atrial fibrillation after cardiac surgery is a common postoperative arrhythmia and has long been considered a clinical issue. It complicates postoperative management due to hemodynamic instability and may lead to complications such as cerebral infarction and prolonged ICU stay [4,6], although the latter claim has not been conclusively proven [7]. Conventional coronary artery bypass surgery has been associated with a high rate of postoperative atrial fibrillation (15–40%). Although the surgical technique has been revised to forego the use of a heart-lung machine, some suggest that the incidence of postoperative atrial fibrillation is not affected by the use of a heart-lung machine [4,5,8]. In general, old age, hypertension, diabetes, and obesity are considered risk factors for postoperative atrial fibrillation [9]. Over time, surgical techniques have improved significantly, and this has resulted in reduced operative time. Notably, perioperative management practices have also changed; for example, many patients are now administered preoperative statins, and some remain on statins up until surgery. The use of remifentanil in cardiac surgical anesthesia has also been on the rise. Magnesium has long been used in the treatment of atrial fibrillation, and the intraoperative use of magnesium-containing infusions have become more common. In some cases, intraoperative short-acting β-blockers are used when needed. However, whether these perioperative changes alter the incidence of postoperative atrial fibrillation has been unclear.

Our data showed that postoperative atrial fibrillation occurred in 29.3% (81/276) of patients. This incidence rate is in accordance with previous studies [2,3]. We further demonstrated that the incidence of postoperative atrial fibrillation was associated with age, left atrial diameter, and intraoperative use of remifentanil. The use of magnesium-containing infusion products, which was expected to be beneficial, was found to have no significant impact. While previous studies demonstrated that magnesium is effective in suppressing postoperative atrial fibrillation [10,11], some indicated that further studies are needed [9]. Although a variety of infusions containing magnesium are available, the amount of Mg [2+]contained in infusions is about 2 mEq/L. Our findings indicate the need to reconsider total infusion volume in future studies. β-blockers are commonly used to treat atrial fibrillation, and their use during the perioperative period is believed to be effective in suppressing postoperative atrial fibrillation. While these studies administered β-blockers for several days [12], we demonstrated that intraoperative use of β-blockers for a very short period of time had no suppressive effect on atrial fibrillation. β-blockers must be used carefully as the perioperative use of β-blockers has been associated with an elevated risk of cerebral infarction [13]. Statins have various pharmacological effects, such as anti-inflammation and plaque reduction and stabilization. They are often taken perioperatively without cessation. Although statins were initially thought to prevent postoperative atrial fibrillation [14,15], a subsequent large study demonstrated that it had negative effects including a risk to renal function [16,17]. Our results indicated that the use of statins had no effect on postoperative atrial fibrillation.

We demonstrated that the use of remifentanil may reduce the incidence of postoperative atrial fibrillation. Remifentanil has analgesic properties, and it has been previously indicated to suppress inflammatory responses [18]. This anti-inflammatory effect may have suppressed the occurrence of postoperative atrial fibrillation. However, remifentanil has also been associated with opioid-induced hyperalgesia, and postoperative pain augmentation may excite the sympathetic nervous system, contributing to the development of atrial fibrillation [19,20]. Thus, remifentanil use should be carefully considered.

This study had certain limitations. First, we examined the effect of drugs and infusions based on their use and did not examine the dose or the duration of administration. Future studies should evaluate the dose and duration of administration.

Second, all patients with atrial fibrillation listed in the medical record were included in the study, and the need for treatment was not considered. Previous studies also did not include clear distinction. Thus, future studies should be developed based on the discussion on how to define atrial fibrillation. Third, old data was used in this study. It is necessary to incorporate new data in the future.

Our findings suggest that the anti-inflammatory effect of remifentanil could suppress atrial fibrillation. This raises a question as to whether other anti-inflammatory drugs such as dexmedetomidine and remimazolam would also have similar effects [21,22]. In Japan, remifentanil was approved for use in postoperative ICU settings in 2023. The effect of long-term use of remimazolam and remifentanil on postoperative atrial fibrillation is currently unknown.

5. Conclusions

Intraoperative use of remifentanil may be effective in reducing the incidence of postoperative atrial fibrillation. Future studies are needed to determine appropriate dosage and its combination with other drugs.

Fig. 1 Flowchart of the study.

Table 1 Comparison of baseline data and perioperative findings.

	Postoperative atrial fibrillation (+)	Postoperative atrial fibrillation (−)	P	
Age (Yr)	72 (66–77)	69 (60.5–74)	0.007	
Sex (male)	68 (84.0%)	158 (81.0%)	0.566	
Height (cm)	165 (157.3–169)	163.2 (157.2–169)	0.49	
Weight (kg)	63.1 ± 13.6	62.1 ± 10.8	0.512	
HbA1c (%)	6.4 (5.9–7.2)	6.4 (5.9–7.2)	0.773	
Preoperative left atrial diameter (mm)	40.1 (36.3–44.1)	38.1 (35.4–41.6)	0.006	
Preoperative left ventricular ejection fraction (%)	57 (49–61)	59 (47–65)	0.415	
Preoperative Statin use (n)	52	141	0.181	
Operative time (min)	239.8 ± 61.6	227.1 ± 60.5	0.115	
Intraoperative remifentanil use (n)	40	123	0.035	
Intraoperative β-blocker use (n)	14	36	0.817	
Intraoperative Magnesium-containing infusions use (n)	17	32	0.365	
Intraoperative In–Out balance (mL)	3547 (2512–4115)	3322 (2590–4100)	0.598	
Intraoperative number of anastomotic sites (n)	4 (3–4)	3 (3–4)	0.224	

Table 2 Factors associated with the incidence of Atrial fibrillation in both univariate and multivariate logistic regression analysis.

	Univariate	Multivariable	
		
OR	95%CI	P	OR	95%CI	P	
Sex (male)	1.225	0.613–2.449	0.566	1.233	0.587–2.588	0.581	
Age	1.038	1.010–1.067	0.007	1.045	1.015–1.076	0.003	
Preoperative left atrial diameter	1.067	1.021–1.115	0.004	1.072	1.023–1.124	0.004	
Remifentanil use	0.571	0.338–0.964	0.036	0.492	0.284–0.852	0.011	

Conflict of interest: All authors have no conflict of interest.

Author contributions: Conception and design of Study: YI, HK. Literature review: YI, SH, MI, TM, MO. Acquisition of data: YI, SH, MI, TM, MO. Analysis and interpretation of data: YI, HK. Research investigation and analysis: YI, SH, MI, TM, MO. Data collection: YI, SH, MI, TM, MO. Drafting of manuscript: YI, HK. Revising and editing the manuscript critically for important intellectual contents: YI, SH, HK. Data preparation and presentation: YI, MO. Supervision of the research: YI, HK. Research coordination and management: YI, HK. Funding for the research: YI, HK.

Disclosure of funding: All authors receive no funding.
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References

1 Maisel WH Rawn JD Stevenson G Atrial fibrillation after cardiac surgery Ann Intern Med 2001 135 1061 73 10.7326/0003-4819-135-12-200112180-00010 11747385
2 El-Chami MF Kilgo P Thourani V Lattouf OM Delurgio DB Guyton RA New-onset atrial fibrillation predicts long-term mortality after coronary artery bypass graft J Am Coll Cardiol 2010 55 1370 6 10.1016/j.jacc.2009.10.058 20338499
3 Rollo P Postoperative atrial fibri llation and Mortality after coronary artery bypass surgery J Am Coll Cardiol 2004 43 742 8 10.1016/j.jacc.2003.11.023 14998610
4 Hossein G Predictors and impact of postoperative atrial fibrillation on patinets’outcomes:A report from the Randomized on versus off Bypass trial J Thorac Cardiovasc Surg 2012 143 93 102 10.1016/j.jtcvs.2011.10.003 22054659
5 Andre L Off-pump or on-pump coronary-artery bypass grafting at 30 days N Engl J Med 2012 366 1489 97 10.1056/NEJMoa1200388 22449296
6 Almassi GH Schowalter T Nicolosi AC Aggarwal A Moritz TE Henderson WG Atrial fibrillation after cardiac surgery: a major morbid event? Ann Surg 1997 226 501 11 10.1097/00000658-199710000-00011 9351718
7 Chen L Dai W Effects of short-term episodes of atrial fibrillation after coronary artery bypass grafting on the long-term incidence of atrial fibrillation and ischemic stroke Heart Surg Forum 2024 27 E014 9 10.59958/hsf.6787 38286644
8 Arslan G The incidence of atrial fibrillation after on-pump versus off-pump coronary artery bypass grafting Heart Surg Forum 2021 24 E645 50 10.1532/hsf.3873 34473036
9 Omae T Inada E New-Onset atrial fibrillation : an update J Anesth 2018 32 414 24 10.1007/s00540-018-2478-8 29523996
10 Miller S Effects of magnesium on atrial fibrillation after cardiac surgery: a meta-analysis Heart 2005 91 618 23 10.1136/hrt.2004.033811 15831645
11 Burgess DC Interventions for prevention of post-operative atrial fibrillation and its complications after cardiac surgery:a meta-analysis Eur Heart J 2006 27 2846 57 10.1093/eurheartj/ehl272 17015402
12 Tamura T Yatabe T Yokoyama M Prevention of atrial fibrillation after cardiac surgery using low-dose landiolol: a systematic review and meta-analysis J Clin Anesth 2017 42 1 6 10.1016/j.jclinane.2017.07.009 28962938
13 Bangalore S Wetterslev J Pranesh S Sawhney S Gluud C Messerli GF Perioperative β blockers in patients having non-cardiac surgery: a meta-analysis Lancet 2008 372 1962 76 10.1016/S0140-6736(08)61560-3 19012955
14 Mariscalco G Lorusso R Klersy C Ferrarese S Tozzi M Vanoli D Observational study on the beneficial effect of preoperative statins in reducing atrial fibrillation after coronary surgery Ann Thorac Surg 2007 84 1158 65 10.1016/j.athoracsur.2007.05.021 17888963
15 Winchester DE Wen X Xie L Bavry AA Evidence of pre-procedural statin therapy J Am Coll Cardiol 2010 56 1099 109 10.1016/j.jacc.2010.04.023 20825761
16 Zheng Z Jayaram R Jiang L Emberson J Zhao Y Li Q Prioperative rosuvastatin in cardiac surgery N Engl J Med 2016 374 1744 53 10.1056/NEJMoa1507750 27144849
17 Putzu A Capelli B Belletti A Cassina T Ferrari E Gallo M Perioperative statin therapy in cardiac surgery: a meta-analysis of randomized controlled trials Crit Care 2016 20 395 10.1186/s13054-016-1560-6 27919293
18 Hasegawa A Iwasaka H Hagiwara S Hasegawa R Kudo K Kusaka J Remifentanil and glucose suppress inflammation in a rat model of surgical stress Surg Today 2011 41 1617 21 10.1007/s00595-010-4457-z 21969194
19 Santonocito C Noto A Crimi C Sanfilippo F Remifentanil-induced postoperative hyperalgesia: current perspectives on mechanisms and therapeutic strategies Local Reg Anesth 2018 11 15 23 10.2147/LRA.S143618 29670398
20 de Hoogd S Ahlers SJGM van Dongen EPA van de Garde EMW Daeter EJ Dahan A Randomized controlled trial on the influence of intraoperative remifentanil versus fentanyl on acute and chronic pain after cardiac surgery Pain Pract 2018 18 443 51 10.2147/LRA.S143618 28741894
21 Wang K Wu M Xu J Wu C Zhang B Wang G Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis Br J Anaesth 2019 123 777 94 10.1016/j.bja.2019.07.027 31668347
22 Liu X Lin S Zhong Y Shen J Zhang X Luo S Remimazolam protects against LPS-induced endotoxicity improving survival of endotoxemia mice Front Pharmacol 2021 12 10.3389/fphar.2021.739603
