CLINICAL RESEARCH
Europace (2014) 16, 1000–1006 doi:10.1093/europace/eut365
Ablation for atrial fibrillation
Improved sedation with dexmedetomidine– remifentanil compared with midazolam– remifentanil during catheter ablation of atrial fibrillation: a randomized, controlled trial Jin Sun Cho 1, Jae-Kwang Shim 1,2, Sungwon Na 1,2, Inhye Park 1, and Young Lan Kwak 1,2,3* 1 Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea; 2Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 120-752, South Korea; and 3Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752, South Korea
Received 22 August 2013; accepted after revision 27 October 2013; online publish-ahead-of-print 30 December 2013
Aims
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Catheter ablation † Conscious sedation † Dexmedetomidine † Remifentanil † Midazolam
Introduction Treatment of atrial fibrillation (A-fib) by ablation is commonly performed with cardiac catheterization outside of the operating theatre.1 Although ablation of A-fib is far less invasive than the Maze procedure, considerable patient discomfort occurs due to delivery of radiofrequency energy and the length of the procedure (2– 4 h). Specific anaesthetic care is required for ablation of A-fib, because deep sedation and analgesia are essential. The patient must be lying down and motionless to achieve accurate mapping and ablation. Moreover, it may be necessary to deepen the sedation
level during the procedure to achieve cardioversion. Conscious sedation is advocated to readily detect serious procedure-related complications. Therefore, ablation for the treatment of A-fib imposes a significant challenge to anaesthetic providers, because anaesthesia to satisfy the above-mentioned features may be accompanied by respiratory depression and hypotension. Combinations of sedative agents, such as midazolam or propofol with analgesic agents, including fentanyl or remifentanil, are often used for catheter ablation of A-fib.2,3 However, midazolam and propofol lack analgesic effects. Thus, a considerable amount of opioid must also be administered. Opioids frequently cause hypotension,
* Corresponding author. Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea. Tel: +82 2 2228 8513; fax: +82 2 364 2951, Email: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: [email protected].
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Anaesthesia is required for catheter ablation of atrial fibrillation (A-fib) to achieve patient comfort and immobilization to avoid map shifts. This study compared the analgesic and sedative efficacies of dexmedetomidine –remifentanil with those of midazolam–remifentanil for catheter ablation of A-fib. ..................................................................................................................................................................................... Methods Ninety patients were randomized to receive either intermittent midazolam boluses (1– 2 mg) with 3.6 –7.2 mg/kg/h of and results remifentanil (MR group) or dexmedetomidine 0.2 –0.7 mg/kg/h after a loading dose of 1 mg/kg with 1.2 –2.4 mg/kg/h of remifentanil (DR group). The sedation level assessed by the Ramsay sedation and bispectral index scores, haemodynamic variables, pain score (10-point numerical scale), and satisfaction levels of the patients and cardiologists (5-point numerical scale) were recorded. The Ramsay sedation score was significantly higher, and the bispectral index score was lower in the DR group (P , 0.001) compared with the MR group starting 10 min after drug administration. The incidence of desaturation (SpO2 , 90%) was significantly greater in the MR group compared with the DR group (15 vs. 1, P , 0.001). The pain score was significantly lower (1.72 + 1.65 vs. 0.95 + 1.10, P ¼ 0.021), and the satisfaction levels of interventionists were significantly higher (2.50 + 0.71 vs. 3.00 + 0.63, P ¼ 0.001) in the DR group compared with the MR group. ..................................................................................................................................................................................... Conclusion The combination of dexmedetomidine and remifentanil provided deeper sedation, less respiratory depression, better analgesia, and higher satisfaction for the interventionist during catheter ablation of A-fib compared with midazolam plus remifentanil, even at a lower dose of remifentanil.
Improved sedation with DR compared with MR during catheter ablation of A-fib
What’s new? † Conventional combinations of sedative and analgesic agents for ablation of atrial fibrillation achieve insufficient levels of sedation or analgesia and cause respiratory depression. † Dexmedetomidine is an a-2 agonist with sedative and analgesic effects and causes minimal respiratory depression. † The combination of dexmedetomidine and remifentanil achieved a deeper level of sedation, improved analgesic effects, and less respiratory depression during catheter ablation of atrial fibrillation compared with midazolam plus remifentanil, even at a lower dose of remifentanil.
Materials and methods We received approval from our institutional review board for this study. Each patient provided consent for this study. We included 90 patients scheduled for elective catheter ablation for persistent A-fib. Patients were between 20 and 70 years old. Patients with an American Society of Anesthesiologists (ASA) physical status classification ≥3, respiratory disease, or end-stage renal disease were excluded. Patients who were excluded from the study received conscious sedation, primarily with remifentanil combined with midazolam, propofol, or ketamine, as required. When the patient arrived at the electrophysiology study unit, an intravenous catheter was inserted. All patients were monitored with an electrocardiogram. In addition, non-invasive blood pressure, oxygen saturation (SpO2), and respiratory rate (RR) were examined. All patients received oxygen at 4 L/min via a nasal cannula. Patients were randomly assigned to receive remifentanil in combination with either midazolam (MR group, n ¼ 45) or dexmedetomidine (DR group, n ¼ 45) based on a computerized randomization table. The level of sedation was assessed with the RSS (1¼anxious and agitated, restless; 2¼cooperative, oriented, tranquil; 3¼responsive to verbal commands, drowsy; 4¼asleep, responsive to light stimulation; 5¼asleep, slow response to stimulation; 6¼no response to stimulation) and the BIS (a processed electroencephalographic parameter that provides a measure of sedation depth on a unitless scale from 0 to 100, coma; 0 – 40, deep hypnotic state;
40 – 60, general anaesthesia; 60 – 90, deep-to-light sedation; and 90 – 100, awake). The goal of sedation was to achieve an RSS of 2 – 48,10,11 or BIS of 60 – 80. The doses of midazolam and dexmedetomidine were based on the results of previous studies.2,8,10 – 12 Patients in the MR group received 0.02 – 0.05 mg/kg of midazolam as a bolus. Patients in the DR group received 0.2 –0.7 mg/kg/h of dexmedetomidine after a loading dose of 1.0 mg/kg over 10 min. Remifentanil was infused at a rate of 3.6 – 7.2 mg/kg/h in the MR group and 1.2– 2.4 mg/kg/h in the DR group. We performed a preliminary pilot trial to titrate the dose of remifentanil. We found that remifentanil provided sufficient sedation and analgesia at an infusion rate of 1.2 –2.4 mg/kg/h, which corresponded to one-third of the conventional dosage, when it was combined with dexmedetomidine. Considering the opioid-sparing effect of dexmedetomidine13 – 15 and the results of our preliminary trial, the infusion dose of remifentanil in the DR group was reduced to one-third compared with that in the MR group. Further titration of the drug doses to achieve the targeted sedation level was performed by administering 1 – 2 mg of midazolam in the MR group or by increasing the infusion rate of dexmedetomidine by 0.1 mg/kg/h to a maximum of 0.7 mg/kg/h in the DR group. The infusion rate of remifentanil was also increased by 0.6 mg/kg/h to a maximum of 7.2 mg/kg/h in the MR group or by 0.2 mg/kg/h to a maximum of 2.4 mg/ kg/h in the DR group. The cardiologists and patients were blinded to their assigned group throughout the procedure. Haemodynamic variables, including mean arterial pressure (MAP), heart rate (HR), SpO2, and RR, were recorded. Measurements were performed before study drugs were administered (baseline), just after sedation, 5 min thereafter, and every 10 min thereafter. Adverse events, such as bradycardia (HR , 45 b.p.m.), hypotension (MAP , 60 mmHg), and desaturation (SpO2 , 90%), were recorded throughout the procedure. The following measures were taken for adverse events: atropine 0.01 mg/kg intravenously for bradycardia, reduced drug infusion rate and 300 mL of 0.9% salineloading for hypotension, and changing the nasal cannula to a facial oxygen mask (5 L/min) for desaturation. If airway compromise was recognized by desaturation or snoring, the patient was treated by tilting the head, lifting the chin, thrusting the jaw, or inserting a nasal airway. In brief, catheter ablation was performed using the three-dimensional (3D) electroanatomical mapping (NavX; St Jude Medical) merged with 3D spiral computed tomography in all patients. A quadripolar catheter was placed in the ascending aorta and used as a reference point of NavX. An average of 2000 – 3000 mapping points was acquired, and none of the patients required re-mapping or the assistance of other imaging modalities. After the ablation procedure ended, recovery time [the time taken from recovery room arrival to reaching a modified Aldrete score of 9 (a scoring system to measure of recovery after anaesthesia. Numerical scores of 0, 1, or 2 are assigned to motor activity, respiration, circulation, consciousness, and oxygen saturation for a maximal score of 10. A score of 9 is required to be discharged from recovery room.)] and discharge time (recovery room stay: the time taken to achieve haemodynamic stability, alert mental status, and adequate analgesia) were recorded. The satisfaction levels of the patients and cardiologists were assessed with a 5-point numerical scale (0¼extremely dissatisfied, 1¼dissatisfied, 2¼neutral, 3¼satisfied, and 4¼extremely satisfied). The cardiologists were blinded to the group identity and were asked to rate the quality of anaesthetic care. The patients were also asked to rate their levels of satisfaction and pain score with a numerical pain intensity scale (0¼no pain to 10¼the worst pain) throughout the procedure. All statistical analyses were performed with the SPSS 18.0 (SPSSFW, SPSS Inc.) program. The primary endpoint of this study was the level of sedation throughout the procedure. In a previous study, comparing dexmedetomidine and midazolam for sedation during colonoscopy,8 the
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inadequate sedation,4 or respiratory depression which requires advanced airway management.5 Dexmedetomidine is a highly selective a-2 agonist with sedative and analgesic effects,6,7 which has a reduced requirement for other sedative or analgesic agents.8 In contrast to benzodiazepines or opioids, dexmedetomidine causes minimal respiratory depression at effective dose.9 Opioids and/or benzodiazepines may interfere with mapping and ablation, because they can cause slow and exaggerated deep breathing. However, dexmedetomidine provides arousable sedation with minimal changes in respiration. The objective of this prospective, randomized, controlled study was to compare the sedative and analgesic efficacies of dexmedetomidine plus remifentanil with those of midazolam plus remifentanil in patients receiving catheter ablation for A-fib. The primary outcome was sedation level, which was assessed by the Ramsay sedation score (RSS) and bispectral index score (BIS). The incidence of adverse events, the pain score, and the satisfaction of cardiologists and patients were considered as secondary outcomes.
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mean RSS at 10 min after injection was 2.25 in the dexmedetomidine group and 1.75 in the midazolam group. Assuming a difference in RSS between the dexmedetomidine group and the midazolam group of 0.5, we estimated that 41 patients in each group would provide 80% power at an a level of 0.05. We factored in a 10% dropout rate and enroled 45 patients in each group. Data are shown as means with standard deviations. Comparisons between groups were performed with the independent t-test for numerical variable, and the x 2 test or Fisher’s exact test for categorical variables. The normality of distribution was assessed with the Kolmogorov– Smirnov and Shapiro–Wilk test. Intra- and inter-group comparisons of repeatedly measured continuous variables were performed with repeated measures analysis of variance followed by a Bonferroni correction. A P value of ,0.05 was considered statistically significant.
Results The procedure and study were successfully performed in each of the 90 patients enroled in the study. Patient characteristics were similar
between the two groups (Table 1). The procedure time and ablation time did not differ between groups. Comparison of groups based on the levels of sedation assessed with RSS and BIS indicated that sedation was more efficient in the DR group than in the MR group. The RSS and BIS values were comparable in both groups from baseline to 5 min after drug administration. However, the RSS was significantly higher (P , 0.001), and the BIS was significantly lower (P , 0.001) in the DR group compared with the MR group starting 10 min after drug administration (Figure 1). Haemodynamic variables, including HR, SpO2, and RR, were not significantly different between groups throughout the study period (Table 2). Mean arterial pressure in the DR group was significantly lower than that in the MR group at 60 min (105 + 16 vs. 85 + 14 mmHg, P , 0.001) and 120 min (102 + 15 vs. 93 + 16 mmHg, P ¼ 0.043) after drug administration. Intra-group comparisons of haemodynamic variables during the procedure showed that HR, SpO2, and RR were similar to the corresponding baseline values in
Table 1 Demographic data, procedure time, and drug administration DR (n 5 45)
P value
Age (year) Sex (M : F)
56.3 + 9.3 36 : 9
55.2 + 8.7 36 : 9
0.58 1.00
Height (cm)
169.5 + 7.2
168.7 + 8.0
0.62
Weight (kg) BSA
72.9 + 12.2 1.84 + 0.19
ASA physical status I/II
8/37
16/29
0.06
14
14
1.00
6
7
1.00
Coronary artery disease (n) Valve disease (n)
14 7
8 10
0.22 0.59
Previous DC cardioversion (n)
17
History of Hypertension (n) Diabetes mellitus (n)
70.9 + 9.6 1.82 + 0.15
16
0.39 0.49
1.00
Previous atrial fibrillation ablation (n) Left ventricular ejection fraction (%)
9 63.3 + 9.3
10 62.8 + 8.1
1.00 0.788
Left atrial volume index (mL/m2)
35.8 + 12.5
33.1 + 13.7
0.352
Pre-procedural medications Calcium channel blockers (n)
17
26
0.06
b-blockers (n)
15
13
0.65
Renin angiotensin antagonist (n) Diuretics (n)
17 6
11 7
0.17 0.76
Flecainide (n)
8
13
0.21
Sotalol (n) Amiodarone (n)
1 1
0 3
0.32 0.31
0
0.15
Digoxin (n)
2
Procedure time (min) Ablation time (s)
199.7 + 36.7 4278.7 + 1180.5
210.1 + 48.7 4932.3 + 1465.1
0.264 0.256
Remifentanil (mg/kg/h)
3.97 + 0.95
1.80 + 0.74
,0.001*
Midazolam (mg/kg/h) Dexmedetomidine (mg/kg/h)
4.27 + 4.97 0
0 0.40 + 0.20
,0.001* ,0.001*
Values are mean + standard deviation. MR, midazolam –remifentanil group; DR, dexmedetomidine –remifentanil group; BSA, body surface area; ASA, American Society of Anesthesiologists. *P , 0.05 compared with the MR group.
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MR (n 5 45)
...............................................................................................................................................................................
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Improved sedation with DR compared with MR during catheter ablation of A-fib
100
*
*
*
10
60
120
90
BIS
80 70 60 50 Baseline
0
5 min
Midazolam–remifentanil Dexmedetomidine–remifentanil 5 *
RSS
4
*
10
60
3 2 1 0 Baseline
0
5
120
min
Figure 1 Changes in the bispectral index score (BIS) and Ramsay sedation score (RSS). *P , 0.05 compared with the midazolamremifentanil group.
Table 2 Haemodynamic data Baseline
Drug administration
After 5 min
After 10 min
After 60 min
64.7 + 11.2 69.4 + 18.3 98.5 + 13.1 96.6 + 10.9
After 120 min
66.5 + 13.6 68.4 + 19.3
69.8 + 23.7 67.7 + 19.0
67.6 + 16.3 65.7 + 18.2
75.8 + 18.6 70.8 + 23.0
79.3 + 16.5 89.8 + 91.0
98.0 + 19.8 96.9 + 10.9
101.8 + 13.5 96.8 + 11.7
101.0 + 16.2 94.8 + 11.3
104.8 + 15.9 84.6 + 14.3*,†
102.5 + 14.9 92.6 + 16.3*
19.0 + 4.8 19.1 + 16.5
18.3 + 5.6 16.4 + 4.9
17.4 + 4.7 16.2 + 4.4
16.7 + 5.5 15.5 + 4.0
15.6 + 5.4 15.6 + 3.7
16.5 + 5.7 15.8 + 3.9
99.0 + 1.6 97.1 + 12.3
98.8 + 2.0 97.8 + 12.0
98.8 + 2.1 99.5 + 1.9
99.0 + 1.5 99.4 + 1.9
98.6 + 1.9 99.0 + 1.9
98.7 + 1.7 98.9 + 1.6
............................................................................................................................................................................... HR (b.p.m.) MR DR MAP (mmHg) MR DR
Respiratory rate (breaths/min) MR DR SpO2 (%) MR DR
Values are mean + standard deviation. MR, midazolam –remifentanil group; DR, dexmedetomidine –remifentanil group. *P , 0.05 compared with the MR group, †P , 0.05 compared with the baseline value within the group.
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*
both groups. Mean arterial pressure was lower than the baseline value in the DR group 60 min after drug administration (97 + 11 vs. 85 + 14 mmHg, P , 0.001). The incidence of desaturation (SpO2 , 90%) was significantly higher in the MR group than in the DR group (15 vs. 1, P , 0.001). All of the patients with desaturation were successfully managed with oxygen supplementation by facial mask, head elevation, chin lift, or jaw thrust. Therefore, none of the patients required invasive airway management or termination of the procedure. The incidence of bradycardia and nausea/vomiting did not differ between groups. Five patients in the DR group had single episodes of hypotension, which was restored above 60 mmHg by adjusting the drug infusion rate in all of the patients. In contrast, none of the patients in the MR group had episodes of hypotension throughout the study period (P ¼ 0.056). The post-procedural questionnaire showed that the pain score was lower in the DR group than in the MR group (1.7 + 1.7 vs. 1.0 + 1.1, P ¼ 0.021). The satisfaction levels of patients with anaesthesia were similar in both groups, whereas cardiologists were more satisfied with the DR group than with the MR group (2.5 + 0.7 vs. 3.0 + 0.6, P ¼ 0.001, Table 3). There were no significant differences in recovery time between groups according to the modified Aldrete score. The Aldrete score was 9 in most of the patients when they arrived in the recovery room. However, for one patient in the DR group, the Aldrete score reached 9 within 5 min of arriving in the recovery room. The time to discharge did not differ between groups (Table 3). The incidence of procedure-related complications, including haematoma at the puncture site (2 vs. 2), pericarditis (1 vs. 3), pericardial effusion (1 vs. 0), and first-degree atrioventricular block (1 vs. 0) was similar between groups. Recurrence rates of A-fib at the time of discharge from the hospital (4 vs. 1) and 1 year later (11 vs. 11) were also similar between groups (the numbers in the parenthesis are MR vs. DR group).
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Table 3 Incidences of adverse events, recovery time, and satisfaction score MR (n 5 45)
DR (n 5 45)
P value
................................................................................ Bradycardia (,45 b.p.m.)
0 (0%)
1 (2.2%)
1
Hypotension (,60 mmHg)
0 (0%)
5 (11.1%)
0.056
1 (2.2%) 3 (6.7%)
,0.001* 0.485
Desaturation (,90%) Nausea/vomiting Time to recovery (min) Time to discharge (min) Satisfaction score of patients Satisfaction score of cardiologists
15 (33.3%) 6 (13.3%)
0.1 + 0.8
0.324
10.7 + 2.8 2.9 + 0.6
10.0 + 4.2 3.0 + 0.5
0.371 0.460
2.5 + 0.7
3.0 + 0.6
0.001*
0
Values are mean + standard deviation. MR, midazolam –remifentanil group; DR, dexmedetomidine –remifentanil group; Time to recovery, the time taken to reach a modified Aldrete score of 9 from recovery room arrival; Satisfaction level of the patients and cardiologists, 5-point numerical scale. *P , 0.05 compared with the MR group.
In this prospective and randomized study, dexmedetomidine combined with low-dose remifentanil showed superior sedative and analgesic effects compared with the combination of midazolam and remifentanil in patients receiving catheter ablation for A-fib. The dexmedetomidine –remifentanil regimen was also associated with significantly reduced respiratory depression and higher levels of satisfaction among cardiologists. However, dexmedetomidine– remifentanil also showed a trend towards a higher incidence of benign intra-procedural hypotension. During catheter ablation for A-fib, severe pain may result from catheter insertion, cardioversion, or radiofrequency ablation of the pulmonary veins.16,17 In addition, patient movement and/or deep breathing due to co-administration of benzodiazepine and opioids may cause registration errors during acquisition of specific target areas and map shifts during ablation. Importantly, accumulation of pericardial fluid or blood during the ablation procedure may cause mechanical cardiac compression or disrupted haemodynamics, which may be further exacerbated by positive-pressure ventilation.2 Serious complications, such as cardiac tamponade, stroke, or oesophageal damage, may be identified early during the procedure if the patient remains conscious. Thus, conscious sedation is preferred instead of general anaesthesia by some interventionists. Specific anaesthetic management that provides sufficient sedation and analgesia, but also maintains haemodynamic stability and spontaneous ventilation, is challenging but mandatory for catheter ablation of A-fib. Fentanyl –midazolam3 or remifentanil –midazolam2 combinations are commonly used. Propofol infusion has also been reported to be safe and effective for sedation during cardiac ablation procedures.18 However, there are several problems with the conventional regimens. Midazolam and propofol lack analgesic effects, requiring the
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Discussion
additional use of considerable amount of opioids. Opioids can cause serious respiratory depression.19 In a retrospective study of 280 patients receiving cardiac ablation under monitored anaesthetic care with opioids, 40% of patients required an advanced form of airway intervention.4 In addition, opioids are often associated with exaggerated deep breathing, which may magnify the movement of the target area and interfere with accurate ablation. In a study of patients receiving cardioversion, a high dose of midazolam (12.5 + 5.0 mg) was necessary to achieve the desired sedation level. This high dose increased the risk of hypotension and respiratory depression. Moreover, it took 5.0 + 3.4 min to obtain adequate sedation, which was impractical for haemodynamic instability and required immediate cardioversion.5 Administration of propofol as an anaesthetic for cardiac interventions required cessation of propofol infusion and switching to midazolam in 13.6% of patients due to persistent hypotension and in 1.9% of patients because of respiratory depression.18 Dexmedetomidine is a selective a-2 adrenoceptor agonist with analgesic, sedative, and anxiolytic effects and minimal risk of respiratory depression.20 Dexmedetomidine reduces anaesthetic requirement and blunts the sympathetic response to surgical stimulation.21 Dexmedetomidine has been safely used alone or in combination with other sedative/analgesic drugs, including benzodiazepine, ketamine, or opioids, for procedures requiring conscious sedation.8,13 – 15 Considering these potential advantages, dexmedetomidine is an ideal anaesthetic agent for catheter ablation of A-fib, although it was not previously validated. In the current trial, both anaesthetic regimens provided adequate levels of sedation and analgesia, enabling uninterrupted and uneventful ablation in all of the patients. However, the combination of dexmedetomidine with low-dose remifentanil showed superior sedative and analgesic effects compared with the midazolam–remifentanil regimen. This finding is consistent with the results of a previous study that compared the sedative effects of dexmedetomidine and midazolam during colonoscopy.8 In current study, dexmedetomidine was also superior in terms of maintaining adequate respiration and the satisfaction of cardiologists. The well-known opioid- and anaesthetic-sparing effects of dexmedetomidine14,22,23 are due to persistent actions on a-2 adrenoceptor in the spinal cord.24 Dexmedetomidine does not cause severe respiratory depression because of its a-2 adrenergic agonistic action but does provide sufficient sedation and analgesia.13 Accordingly, we observed increased sedation and analgesia in the DR group compared with the MR group despite using one-third of the dose of remifentanil. The opioid-sparing effect and ability to maintain spontaneous ventilation may have significantly reduced respiratory depression and heavy breathing, leading to increased satisfaction among cardiologists. However, dexmedetomidine has the potential to cause hypotension due to systemic vasodilation via sympatholytic actions.20 Dexmedetomidine usually elicits a biphasic haemodynamic response with an initial increase in blood pressure and reflex bradycardia followed by a subsequent return to baseline after stabilization.25 Although patients in the DR group showed a trend towards a higher incidence of hypotension compared with those in the MR group (5 vs. 0, P ¼ 0.056), blood pressure was rapidly restored in all patients only if the infusion rate was reduced within the range of the studied dose. Thus, the chosen dose range in the current trial (0.2– 0.7 mg/
Improved sedation with DR compared with MR during catheter ablation of A-fib
Conclusions We found that dexmedetomidine combined with a three-fold lower dosage of remifentanil achieved improved sedation, reduced respiratory depression, and improved satisfaction for cardiologists compared with the combination of midazolam and remifentanil. A trend towards a higher incidence of intra-procedural hypotension was noted in the dexmedetomidine group. However, this was benign and infrequent. Future large-scale studies should be performed in susceptible patients. Dexmedetomidine combined with remifentanil may be an effective and safe anaesthetic regimen during catheter ablation of A-fib.
Acknowledgements Assistance with the study was provided by Hui-Nam Pak, Professor, and Boyoung Joung, Associate Professor, Cardiology Division, Yonsei Cardiovascular Center and Cardiovascular Research Institute, Yonsei University Health System.
Conflict of interest: none declared.
References 1. Cheema A, Vasamreddy CR, Dalal D, Marine JE, Dong J, Henrikson CA et al. Long-term single procedure efficacy of catheter ablation of atrial fibrillation. J Interv Card Electrophysiol 2006;15:145 – 55. 2. Mandel JE, Hutchinson MD, Marchlinski FE. Remifentanil-midazolam sedation provides hemodynamic stability and comfort during epicardial ablation of ventricular tachycardia. J Cardiovasc Electrophysiol 2011;22:464 – 6. 3. Brugada J, Berruezo A, Cuesta A, Osca J, Chueca E, Fosch X et al. Nonsurgical transthoracic epicardial radiofrequency ablation: an alternative in incessant ventricular tachycardia. J Am Coll Cardiol 2003;41:2036 – 43. 4. Mitchell AR, Chalil S, Boodhoo L, Bordoli G, Patel N, Sulke N. Diazepam or midazolam for external DC cardioversion (the DORM Study). Europace 2003;5:391–5. 5. Trentman TL, Fassett SL, Mueller JT, Altemose GT. Airway interventions in the cardiac electrophysiology laboratory: a retrospective review. J Cardiothorac Vasc Anesth 2009;23:841 –5. 6. Kauppila T, Kemppainen P, Tanila H, Pertovaara A. Effect of systemic medetomidine, an alpha 2 adrenoceptor agonist, on experimental pain in humans. Anesthesiology 1991;74:3 –8. 7. Venn RM, Bradshaw CJ, Spencer R, Brealey D, Caudwell E, Naughton C et al. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia 1999;54:1136 –42. 8. Dere K, Sucullu I, Budak ET, Yeyen S, Filiz AI, Ozkan S et al. A comparison of dexmedetomidine versus midazolam for sedation, pain and hemodynamic control, during colonoscopy under conscious sedation. Eur J Anaesthesiol 2010;27:648 – 52. 9. Arain SR, Ruehlow RM, Uhrich TD, Ebert TJ. The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery. Anesth Analg 2004;98:153 –8. 10. Koruk S, Mizrak A, Gul R, Kilic E, Yendi F, Oner U. Dexmedetomidine-ketamine and midazolam-ketamine combinations for sedation in pediatric patients undergoing extracorporeal shock wave lithotripsy: a randomized prospective study. J Anesth 2010;24:858 –63. 11. McCutcheon CA, Orme RM, Scott DA, Davies MJ, McGlade DP. A comparison of dexmedetomidine versus conventional therapy for sedation and hemodynamic control during carotid endarterectomy performed under regional anesthesia. Anesth Analg 2006;102:668 –75. 12. Tosun Z, Akin A, Guler G, Esmaoglu A, Boyaci A. Dexmedetomidine-ketamine and propofol-ketamine combinations for anesthesia in spontaneously breathing pediatric patients undergoing cardiac catheterization. J Cardiothorac Vasc Anesth 2006;20:515 –9. 13. Kunisawa T, Ueno M, Kurosawa A, Nagashima M, Hayashi D, Sasakawa T et al. Dexmedetomidine can stabilize hemodynamics and spare anesthetics before cardiopulmonary bypass. J Anesth 2011;25:818 –22. 14. Al-Zaben KR, Qudaisat IY, Al-Ghanem SM, Massad IM, Al-Mustafa MM, Al-Oweidi AS et al. Intraoperative administration of dexmedetomidine reduces the analgesic requirements for children undergoing hypospadius surgery. Eur J Anaesthesiol 2010;27:247 –52. 15. Wallace S, Mecklenburg B, Hanling S. Profound reduction in sedation and analgesic requirements using extended dexmedetomidine infusions in a patient with an open abdomen. Mil Med 2009;174:1228 –30. 16. Aryana A, Heist EK, D’Avila A, Holmvang G, Chevalier J, Ruskin JN et al. Pain and anatomical locations of radiofrequency ablation as predictors of esophageal temperature rise during pulmonary vein isolation. J Cardiovasc Electrophysiol 2008;19:32–8. 17. Alaeddini J, Wood MA, Parvez B, Pathak V, Wong KA, Ellenbogen KA. Site localization and characterization of pain during radiofrequency ablation of the pulmonary veins. Pacing Clin Electrophysiol 2007;30:1210 – 4. 18. Salukhe TV, Willems S, Drewitz I, Steven D, Hoffmann BA, Heitmann K et al. Propofol sedation administered by cardiologists without assisted ventilation for long cardiac interventions: an assessment of 1000 consecutive patients undergoing atrial fibrillation ablation. Europace 2012;14:325 –30. 19. Pugsley MK. The diverse molecular mechanisms responsible for the actions of opioids on the cardiovascular system. Pharmacol Ther 2012;93:51–75. 20. Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs 2000;59:263 – 70. 21. Tobias JD, Berkenbosch JW. Initial experience with dexmedetomidine in paediatric-aged patients. Paediatr Anaesth 2002;12:171 –5. 22. Carollo DS, Nossaman BD, Ramadhyani U. Dexmedetomidine: a review of clinical applications. Curr Opin Anaesthesiol 2008;21:457–61. 23. Jalonen J, Hynynen M, Kuitunen A, Heikkila H, Perttila J, Salmenpera M et al. Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. Anesthesiology 1997;86:331 –45. 24. Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg 2000;90: 699 –705.
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kg/h) seems to be safe, which is further supported by a study that reported an increase in the relative risk of developing bradycardia and hypotension (requiring treatment) only after administering a loading dose and maintenance dose of .0.7 mg/kg/h in critically ill patients.26 However, caution should be exercised when using a higher dose range as some studies have reported a tendency for dexmedetomidine-treated patients to require perioperative treatment for hypotension and/or bradycardia.14,27,28 Also, the results of the current trial cannot be extrapolated to patients who have compromised cardiac function. There has been concern regarding the potential of dexmedetomidine to delay recovery. One study reported that dexmedetomidine caused prolonged anaesthetic recovery compared with a combination of midazolam and fentanyl in adult patients undergoing extracorporeal shock wave lithotripsy.29 However, in another study, the combination of dexmedetomidine and ketamine reduced recovery time in comparison with the combination of midazolam and ketamine. Recovery time in that study was assessed by eye-opening, verbal responses, and cooperation time in paediatric patients who received the same procedure.13 Despite continuous infusion of dexmedetomidine for 3 –4 h, we did not observe a prolonged recovery time compared with midazolam. This may be due to repeated administration of midazolam, which may have resulted in prolonged sedation and respiratory depression because the active metabolite has a long half-life (1.8 –6.4 h).30 In contrast, dexmedetomidine undergoes nearly complete hepatic metabolism into inactive metabolites. The half-life of dexmedetomidine is 1.5 –3 h after intravenous injection. Therefore, dexmedetomidine may be easier to titrate and promotes faster recovery if used for a prolonged period of time.13 A limitation of this study is that the attending anaesthesiologist was not blinded to the study group. In contrast, the patients and cardiologists were blinded to the group allocation. Continuous infusion of midazolam throughout the procedure just for blinding purposes might cause excessive sedation, severe hypotension, respiratory depression, or even prolonged recovery. Thus, the attending anaesthesiologist inevitably noticed differences in the groups based on the regimens that each received.
1005
1006 25. Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology 1992;77:1134 –42. 26. Tan JA, Ho KM. Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: a meta-analysis. Intensive Care Med 2010;36: 926 –39. 27. Bekker AY, Basile J, Gold M, Riles T, Adelman M, Cuff G et al. Dexmedetomidine for awake carotid endarterectomy: efficacy, hemodynamic profile, and side effects. J Neurosurg Anesthesiol 2004;16:126 –35.
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28. Talke P, Li J, Jain U, Leung J, Drasner K, Hollenberg M et al. Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. The Study of Perioperative Ischemia Research Group. Anesthesiology 1995;82:620 –33. 29. Zeyneloglu P, Pirat A, Candan S, Kuyumcu S, Tekin I, Arslan G. Dexmedetomidine causes prolonged recovery when compared with midazolam/fentanyl combination in outpatient shock wave lithotripsy. Eur J Anaesthesiol 2008;25:961 –7. 30. Gan TJ. Pharmacokinetic and pharmacodynamic characteristics of medications used for moderate sedation. Clin Pharmacokinet 2006;45:855 –69.
EP CASE EXPRESS
doi:10.1093/europace/eut431 Online publish-ahead-of-print 27 January 2014
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Atrial flutter ablation in a patient with Marfanoid syndrome and anomalous cavotricuspid isthmus Russell Heath, Joseph Kay, and Duy Thai Nguyen* Electrophysiology, Cardiology Division, University of Colorado, Anschutz Medical Campus, 12401 E. 17th Avenue, B-132, Aurora, CO 80045, USA
* Corresponding author. Tel: +1 720 848 0758; fax: +1 720 848 0475, E-mail: [email protected]
The full-length version of this report can be viewed at: http://www. escardio.org/communities/EHRA/publications/ep-case-reports/ Documents/Atrial-flutter-ablation-in-a-patient.pdf.
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected].
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An 18-year-old man, with a Marfanoid connective tissue disorder, presented with atrial flutter (Panel C). He was referred for electrophysiology study and ablation. Entrainment manoeuvres confirmed the presence of typical counterclockwise cavotricuspid isthmus (CTI)dependent atrial flutter (Panel D). On intracardiac echocardiography (ICE; AcuNav, Biosense Webster), an enormous pouch was visualized along the medial CTI, near the tricuspid valve, and adjacent to the coronary sinus (Panel A and Video). Using a 3.5 mm Thermocool catheter (Biosense Webster), ablation lateral and medial to the pouch terminated the atrial flutter with bidirectional block (Panel E). A cardiac magnetic resonance imaging (Panel B) showed that the pouch was, in fact, an atrial anastomosis from the right atrial (RA) floor to an anomalous ‘portal’ vein from the liver (arrow). Cardiac manifestations of Marfan’s syndrome include aortic dilation and aneurysmal formation, leading to aortic dissection or rupture. To our knowledge, structural abnormalities of the atrium and venous anomalies have not been described. Only several cases of atrial flutter and Marfan’s syndrome have been reported, and none have defined RA anatomy by ICE. Intracardiac echocardiography was a valuable tool for ablation in this case and should be considered in patients with connective tissue disorders, as they may be predisposed to aberrant cardiac anatomy.
Europace (2014) 16, 1000–1006 doi:10.1093/europace/eut365
Ablation for atrial fibrillation
Improved sedation with dexmedetomidine– remifentanil compared with midazolam– remifentanil during catheter ablation of atrial fibrillation: a randomized, controlled trial Jin Sun Cho 1, Jae-Kwang Shim 1,2, Sungwon Na 1,2, Inhye Park 1, and Young Lan Kwak 1,2,3* 1 Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea; 2Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 120-752, South Korea; and 3Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752, South Korea
Received 22 August 2013; accepted after revision 27 October 2013; online publish-ahead-of-print 30 December 2013
Aims
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Catheter ablation † Conscious sedation † Dexmedetomidine † Remifentanil † Midazolam
Introduction Treatment of atrial fibrillation (A-fib) by ablation is commonly performed with cardiac catheterization outside of the operating theatre.1 Although ablation of A-fib is far less invasive than the Maze procedure, considerable patient discomfort occurs due to delivery of radiofrequency energy and the length of the procedure (2– 4 h). Specific anaesthetic care is required for ablation of A-fib, because deep sedation and analgesia are essential. The patient must be lying down and motionless to achieve accurate mapping and ablation. Moreover, it may be necessary to deepen the sedation
level during the procedure to achieve cardioversion. Conscious sedation is advocated to readily detect serious procedure-related complications. Therefore, ablation for the treatment of A-fib imposes a significant challenge to anaesthetic providers, because anaesthesia to satisfy the above-mentioned features may be accompanied by respiratory depression and hypotension. Combinations of sedative agents, such as midazolam or propofol with analgesic agents, including fentanyl or remifentanil, are often used for catheter ablation of A-fib.2,3 However, midazolam and propofol lack analgesic effects. Thus, a considerable amount of opioid must also be administered. Opioids frequently cause hypotension,
* Corresponding author. Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea. Tel: +82 2 2228 8513; fax: +82 2 364 2951, Email: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: [email protected].
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Anaesthesia is required for catheter ablation of atrial fibrillation (A-fib) to achieve patient comfort and immobilization to avoid map shifts. This study compared the analgesic and sedative efficacies of dexmedetomidine –remifentanil with those of midazolam–remifentanil for catheter ablation of A-fib. ..................................................................................................................................................................................... Methods Ninety patients were randomized to receive either intermittent midazolam boluses (1– 2 mg) with 3.6 –7.2 mg/kg/h of and results remifentanil (MR group) or dexmedetomidine 0.2 –0.7 mg/kg/h after a loading dose of 1 mg/kg with 1.2 –2.4 mg/kg/h of remifentanil (DR group). The sedation level assessed by the Ramsay sedation and bispectral index scores, haemodynamic variables, pain score (10-point numerical scale), and satisfaction levels of the patients and cardiologists (5-point numerical scale) were recorded. The Ramsay sedation score was significantly higher, and the bispectral index score was lower in the DR group (P , 0.001) compared with the MR group starting 10 min after drug administration. The incidence of desaturation (SpO2 , 90%) was significantly greater in the MR group compared with the DR group (15 vs. 1, P , 0.001). The pain score was significantly lower (1.72 + 1.65 vs. 0.95 + 1.10, P ¼ 0.021), and the satisfaction levels of interventionists were significantly higher (2.50 + 0.71 vs. 3.00 + 0.63, P ¼ 0.001) in the DR group compared with the MR group. ..................................................................................................................................................................................... Conclusion The combination of dexmedetomidine and remifentanil provided deeper sedation, less respiratory depression, better analgesia, and higher satisfaction for the interventionist during catheter ablation of A-fib compared with midazolam plus remifentanil, even at a lower dose of remifentanil.
Improved sedation with DR compared with MR during catheter ablation of A-fib
What’s new? † Conventional combinations of sedative and analgesic agents for ablation of atrial fibrillation achieve insufficient levels of sedation or analgesia and cause respiratory depression. † Dexmedetomidine is an a-2 agonist with sedative and analgesic effects and causes minimal respiratory depression. † The combination of dexmedetomidine and remifentanil achieved a deeper level of sedation, improved analgesic effects, and less respiratory depression during catheter ablation of atrial fibrillation compared with midazolam plus remifentanil, even at a lower dose of remifentanil.
Materials and methods We received approval from our institutional review board for this study. Each patient provided consent for this study. We included 90 patients scheduled for elective catheter ablation for persistent A-fib. Patients were between 20 and 70 years old. Patients with an American Society of Anesthesiologists (ASA) physical status classification ≥3, respiratory disease, or end-stage renal disease were excluded. Patients who were excluded from the study received conscious sedation, primarily with remifentanil combined with midazolam, propofol, or ketamine, as required. When the patient arrived at the electrophysiology study unit, an intravenous catheter was inserted. All patients were monitored with an electrocardiogram. In addition, non-invasive blood pressure, oxygen saturation (SpO2), and respiratory rate (RR) were examined. All patients received oxygen at 4 L/min via a nasal cannula. Patients were randomly assigned to receive remifentanil in combination with either midazolam (MR group, n ¼ 45) or dexmedetomidine (DR group, n ¼ 45) based on a computerized randomization table. The level of sedation was assessed with the RSS (1¼anxious and agitated, restless; 2¼cooperative, oriented, tranquil; 3¼responsive to verbal commands, drowsy; 4¼asleep, responsive to light stimulation; 5¼asleep, slow response to stimulation; 6¼no response to stimulation) and the BIS (a processed electroencephalographic parameter that provides a measure of sedation depth on a unitless scale from 0 to 100, coma; 0 – 40, deep hypnotic state;
40 – 60, general anaesthesia; 60 – 90, deep-to-light sedation; and 90 – 100, awake). The goal of sedation was to achieve an RSS of 2 – 48,10,11 or BIS of 60 – 80. The doses of midazolam and dexmedetomidine were based on the results of previous studies.2,8,10 – 12 Patients in the MR group received 0.02 – 0.05 mg/kg of midazolam as a bolus. Patients in the DR group received 0.2 –0.7 mg/kg/h of dexmedetomidine after a loading dose of 1.0 mg/kg over 10 min. Remifentanil was infused at a rate of 3.6 – 7.2 mg/kg/h in the MR group and 1.2– 2.4 mg/kg/h in the DR group. We performed a preliminary pilot trial to titrate the dose of remifentanil. We found that remifentanil provided sufficient sedation and analgesia at an infusion rate of 1.2 –2.4 mg/kg/h, which corresponded to one-third of the conventional dosage, when it was combined with dexmedetomidine. Considering the opioid-sparing effect of dexmedetomidine13 – 15 and the results of our preliminary trial, the infusion dose of remifentanil in the DR group was reduced to one-third compared with that in the MR group. Further titration of the drug doses to achieve the targeted sedation level was performed by administering 1 – 2 mg of midazolam in the MR group or by increasing the infusion rate of dexmedetomidine by 0.1 mg/kg/h to a maximum of 0.7 mg/kg/h in the DR group. The infusion rate of remifentanil was also increased by 0.6 mg/kg/h to a maximum of 7.2 mg/kg/h in the MR group or by 0.2 mg/kg/h to a maximum of 2.4 mg/ kg/h in the DR group. The cardiologists and patients were blinded to their assigned group throughout the procedure. Haemodynamic variables, including mean arterial pressure (MAP), heart rate (HR), SpO2, and RR, were recorded. Measurements were performed before study drugs were administered (baseline), just after sedation, 5 min thereafter, and every 10 min thereafter. Adverse events, such as bradycardia (HR , 45 b.p.m.), hypotension (MAP , 60 mmHg), and desaturation (SpO2 , 90%), were recorded throughout the procedure. The following measures were taken for adverse events: atropine 0.01 mg/kg intravenously for bradycardia, reduced drug infusion rate and 300 mL of 0.9% salineloading for hypotension, and changing the nasal cannula to a facial oxygen mask (5 L/min) for desaturation. If airway compromise was recognized by desaturation or snoring, the patient was treated by tilting the head, lifting the chin, thrusting the jaw, or inserting a nasal airway. In brief, catheter ablation was performed using the three-dimensional (3D) electroanatomical mapping (NavX; St Jude Medical) merged with 3D spiral computed tomography in all patients. A quadripolar catheter was placed in the ascending aorta and used as a reference point of NavX. An average of 2000 – 3000 mapping points was acquired, and none of the patients required re-mapping or the assistance of other imaging modalities. After the ablation procedure ended, recovery time [the time taken from recovery room arrival to reaching a modified Aldrete score of 9 (a scoring system to measure of recovery after anaesthesia. Numerical scores of 0, 1, or 2 are assigned to motor activity, respiration, circulation, consciousness, and oxygen saturation for a maximal score of 10. A score of 9 is required to be discharged from recovery room.)] and discharge time (recovery room stay: the time taken to achieve haemodynamic stability, alert mental status, and adequate analgesia) were recorded. The satisfaction levels of the patients and cardiologists were assessed with a 5-point numerical scale (0¼extremely dissatisfied, 1¼dissatisfied, 2¼neutral, 3¼satisfied, and 4¼extremely satisfied). The cardiologists were blinded to the group identity and were asked to rate the quality of anaesthetic care. The patients were also asked to rate their levels of satisfaction and pain score with a numerical pain intensity scale (0¼no pain to 10¼the worst pain) throughout the procedure. All statistical analyses were performed with the SPSS 18.0 (SPSSFW, SPSS Inc.) program. The primary endpoint of this study was the level of sedation throughout the procedure. In a previous study, comparing dexmedetomidine and midazolam for sedation during colonoscopy,8 the
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inadequate sedation,4 or respiratory depression which requires advanced airway management.5 Dexmedetomidine is a highly selective a-2 agonist with sedative and analgesic effects,6,7 which has a reduced requirement for other sedative or analgesic agents.8 In contrast to benzodiazepines or opioids, dexmedetomidine causes minimal respiratory depression at effective dose.9 Opioids and/or benzodiazepines may interfere with mapping and ablation, because they can cause slow and exaggerated deep breathing. However, dexmedetomidine provides arousable sedation with minimal changes in respiration. The objective of this prospective, randomized, controlled study was to compare the sedative and analgesic efficacies of dexmedetomidine plus remifentanil with those of midazolam plus remifentanil in patients receiving catheter ablation for A-fib. The primary outcome was sedation level, which was assessed by the Ramsay sedation score (RSS) and bispectral index score (BIS). The incidence of adverse events, the pain score, and the satisfaction of cardiologists and patients were considered as secondary outcomes.
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mean RSS at 10 min after injection was 2.25 in the dexmedetomidine group and 1.75 in the midazolam group. Assuming a difference in RSS between the dexmedetomidine group and the midazolam group of 0.5, we estimated that 41 patients in each group would provide 80% power at an a level of 0.05. We factored in a 10% dropout rate and enroled 45 patients in each group. Data are shown as means with standard deviations. Comparisons between groups were performed with the independent t-test for numerical variable, and the x 2 test or Fisher’s exact test for categorical variables. The normality of distribution was assessed with the Kolmogorov– Smirnov and Shapiro–Wilk test. Intra- and inter-group comparisons of repeatedly measured continuous variables were performed with repeated measures analysis of variance followed by a Bonferroni correction. A P value of ,0.05 was considered statistically significant.
Results The procedure and study were successfully performed in each of the 90 patients enroled in the study. Patient characteristics were similar
between the two groups (Table 1). The procedure time and ablation time did not differ between groups. Comparison of groups based on the levels of sedation assessed with RSS and BIS indicated that sedation was more efficient in the DR group than in the MR group. The RSS and BIS values were comparable in both groups from baseline to 5 min after drug administration. However, the RSS was significantly higher (P , 0.001), and the BIS was significantly lower (P , 0.001) in the DR group compared with the MR group starting 10 min after drug administration (Figure 1). Haemodynamic variables, including HR, SpO2, and RR, were not significantly different between groups throughout the study period (Table 2). Mean arterial pressure in the DR group was significantly lower than that in the MR group at 60 min (105 + 16 vs. 85 + 14 mmHg, P , 0.001) and 120 min (102 + 15 vs. 93 + 16 mmHg, P ¼ 0.043) after drug administration. Intra-group comparisons of haemodynamic variables during the procedure showed that HR, SpO2, and RR were similar to the corresponding baseline values in
Table 1 Demographic data, procedure time, and drug administration DR (n 5 45)
P value
Age (year) Sex (M : F)
56.3 + 9.3 36 : 9
55.2 + 8.7 36 : 9
0.58 1.00
Height (cm)
169.5 + 7.2
168.7 + 8.0
0.62
Weight (kg) BSA
72.9 + 12.2 1.84 + 0.19
ASA physical status I/II
8/37
16/29
0.06
14
14
1.00
6
7
1.00
Coronary artery disease (n) Valve disease (n)
14 7
8 10
0.22 0.59
Previous DC cardioversion (n)
17
History of Hypertension (n) Diabetes mellitus (n)
70.9 + 9.6 1.82 + 0.15
16
0.39 0.49
1.00
Previous atrial fibrillation ablation (n) Left ventricular ejection fraction (%)
9 63.3 + 9.3
10 62.8 + 8.1
1.00 0.788
Left atrial volume index (mL/m2)
35.8 + 12.5
33.1 + 13.7
0.352
Pre-procedural medications Calcium channel blockers (n)
17
26
0.06
b-blockers (n)
15
13
0.65
Renin angiotensin antagonist (n) Diuretics (n)
17 6
11 7
0.17 0.76
Flecainide (n)
8
13
0.21
Sotalol (n) Amiodarone (n)
1 1
0 3
0.32 0.31
0
0.15
Digoxin (n)
2
Procedure time (min) Ablation time (s)
199.7 + 36.7 4278.7 + 1180.5
210.1 + 48.7 4932.3 + 1465.1
0.264 0.256
Remifentanil (mg/kg/h)
3.97 + 0.95
1.80 + 0.74
,0.001*
Midazolam (mg/kg/h) Dexmedetomidine (mg/kg/h)
4.27 + 4.97 0
0 0.40 + 0.20
,0.001* ,0.001*
Values are mean + standard deviation. MR, midazolam –remifentanil group; DR, dexmedetomidine –remifentanil group; BSA, body surface area; ASA, American Society of Anesthesiologists. *P , 0.05 compared with the MR group.
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MR (n 5 45)
...............................................................................................................................................................................
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Improved sedation with DR compared with MR during catheter ablation of A-fib
100
*
*
*
10
60
120
90
BIS
80 70 60 50 Baseline
0
5 min
Midazolam–remifentanil Dexmedetomidine–remifentanil 5 *
RSS
4
*
10
60
3 2 1 0 Baseline
0
5
120
min
Figure 1 Changes in the bispectral index score (BIS) and Ramsay sedation score (RSS). *P , 0.05 compared with the midazolamremifentanil group.
Table 2 Haemodynamic data Baseline
Drug administration
After 5 min
After 10 min
After 60 min
64.7 + 11.2 69.4 + 18.3 98.5 + 13.1 96.6 + 10.9
After 120 min
66.5 + 13.6 68.4 + 19.3
69.8 + 23.7 67.7 + 19.0
67.6 + 16.3 65.7 + 18.2
75.8 + 18.6 70.8 + 23.0
79.3 + 16.5 89.8 + 91.0
98.0 + 19.8 96.9 + 10.9
101.8 + 13.5 96.8 + 11.7
101.0 + 16.2 94.8 + 11.3
104.8 + 15.9 84.6 + 14.3*,†
102.5 + 14.9 92.6 + 16.3*
19.0 + 4.8 19.1 + 16.5
18.3 + 5.6 16.4 + 4.9
17.4 + 4.7 16.2 + 4.4
16.7 + 5.5 15.5 + 4.0
15.6 + 5.4 15.6 + 3.7
16.5 + 5.7 15.8 + 3.9
99.0 + 1.6 97.1 + 12.3
98.8 + 2.0 97.8 + 12.0
98.8 + 2.1 99.5 + 1.9
99.0 + 1.5 99.4 + 1.9
98.6 + 1.9 99.0 + 1.9
98.7 + 1.7 98.9 + 1.6
............................................................................................................................................................................... HR (b.p.m.) MR DR MAP (mmHg) MR DR
Respiratory rate (breaths/min) MR DR SpO2 (%) MR DR
Values are mean + standard deviation. MR, midazolam –remifentanil group; DR, dexmedetomidine –remifentanil group. *P , 0.05 compared with the MR group, †P , 0.05 compared with the baseline value within the group.
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*
both groups. Mean arterial pressure was lower than the baseline value in the DR group 60 min after drug administration (97 + 11 vs. 85 + 14 mmHg, P , 0.001). The incidence of desaturation (SpO2 , 90%) was significantly higher in the MR group than in the DR group (15 vs. 1, P , 0.001). All of the patients with desaturation were successfully managed with oxygen supplementation by facial mask, head elevation, chin lift, or jaw thrust. Therefore, none of the patients required invasive airway management or termination of the procedure. The incidence of bradycardia and nausea/vomiting did not differ between groups. Five patients in the DR group had single episodes of hypotension, which was restored above 60 mmHg by adjusting the drug infusion rate in all of the patients. In contrast, none of the patients in the MR group had episodes of hypotension throughout the study period (P ¼ 0.056). The post-procedural questionnaire showed that the pain score was lower in the DR group than in the MR group (1.7 + 1.7 vs. 1.0 + 1.1, P ¼ 0.021). The satisfaction levels of patients with anaesthesia were similar in both groups, whereas cardiologists were more satisfied with the DR group than with the MR group (2.5 + 0.7 vs. 3.0 + 0.6, P ¼ 0.001, Table 3). There were no significant differences in recovery time between groups according to the modified Aldrete score. The Aldrete score was 9 in most of the patients when they arrived in the recovery room. However, for one patient in the DR group, the Aldrete score reached 9 within 5 min of arriving in the recovery room. The time to discharge did not differ between groups (Table 3). The incidence of procedure-related complications, including haematoma at the puncture site (2 vs. 2), pericarditis (1 vs. 3), pericardial effusion (1 vs. 0), and first-degree atrioventricular block (1 vs. 0) was similar between groups. Recurrence rates of A-fib at the time of discharge from the hospital (4 vs. 1) and 1 year later (11 vs. 11) were also similar between groups (the numbers in the parenthesis are MR vs. DR group).
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Table 3 Incidences of adverse events, recovery time, and satisfaction score MR (n 5 45)
DR (n 5 45)
P value
................................................................................ Bradycardia (,45 b.p.m.)
0 (0%)
1 (2.2%)
1
Hypotension (,60 mmHg)
0 (0%)
5 (11.1%)
0.056
1 (2.2%) 3 (6.7%)
,0.001* 0.485
Desaturation (,90%) Nausea/vomiting Time to recovery (min) Time to discharge (min) Satisfaction score of patients Satisfaction score of cardiologists
15 (33.3%) 6 (13.3%)
0.1 + 0.8
0.324
10.7 + 2.8 2.9 + 0.6
10.0 + 4.2 3.0 + 0.5
0.371 0.460
2.5 + 0.7
3.0 + 0.6
0.001*
0
Values are mean + standard deviation. MR, midazolam –remifentanil group; DR, dexmedetomidine –remifentanil group; Time to recovery, the time taken to reach a modified Aldrete score of 9 from recovery room arrival; Satisfaction level of the patients and cardiologists, 5-point numerical scale. *P , 0.05 compared with the MR group.
In this prospective and randomized study, dexmedetomidine combined with low-dose remifentanil showed superior sedative and analgesic effects compared with the combination of midazolam and remifentanil in patients receiving catheter ablation for A-fib. The dexmedetomidine –remifentanil regimen was also associated with significantly reduced respiratory depression and higher levels of satisfaction among cardiologists. However, dexmedetomidine– remifentanil also showed a trend towards a higher incidence of benign intra-procedural hypotension. During catheter ablation for A-fib, severe pain may result from catheter insertion, cardioversion, or radiofrequency ablation of the pulmonary veins.16,17 In addition, patient movement and/or deep breathing due to co-administration of benzodiazepine and opioids may cause registration errors during acquisition of specific target areas and map shifts during ablation. Importantly, accumulation of pericardial fluid or blood during the ablation procedure may cause mechanical cardiac compression or disrupted haemodynamics, which may be further exacerbated by positive-pressure ventilation.2 Serious complications, such as cardiac tamponade, stroke, or oesophageal damage, may be identified early during the procedure if the patient remains conscious. Thus, conscious sedation is preferred instead of general anaesthesia by some interventionists. Specific anaesthetic management that provides sufficient sedation and analgesia, but also maintains haemodynamic stability and spontaneous ventilation, is challenging but mandatory for catheter ablation of A-fib. Fentanyl –midazolam3 or remifentanil –midazolam2 combinations are commonly used. Propofol infusion has also been reported to be safe and effective for sedation during cardiac ablation procedures.18 However, there are several problems with the conventional regimens. Midazolam and propofol lack analgesic effects, requiring the
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Discussion
additional use of considerable amount of opioids. Opioids can cause serious respiratory depression.19 In a retrospective study of 280 patients receiving cardiac ablation under monitored anaesthetic care with opioids, 40% of patients required an advanced form of airway intervention.4 In addition, opioids are often associated with exaggerated deep breathing, which may magnify the movement of the target area and interfere with accurate ablation. In a study of patients receiving cardioversion, a high dose of midazolam (12.5 + 5.0 mg) was necessary to achieve the desired sedation level. This high dose increased the risk of hypotension and respiratory depression. Moreover, it took 5.0 + 3.4 min to obtain adequate sedation, which was impractical for haemodynamic instability and required immediate cardioversion.5 Administration of propofol as an anaesthetic for cardiac interventions required cessation of propofol infusion and switching to midazolam in 13.6% of patients due to persistent hypotension and in 1.9% of patients because of respiratory depression.18 Dexmedetomidine is a selective a-2 adrenoceptor agonist with analgesic, sedative, and anxiolytic effects and minimal risk of respiratory depression.20 Dexmedetomidine reduces anaesthetic requirement and blunts the sympathetic response to surgical stimulation.21 Dexmedetomidine has been safely used alone or in combination with other sedative/analgesic drugs, including benzodiazepine, ketamine, or opioids, for procedures requiring conscious sedation.8,13 – 15 Considering these potential advantages, dexmedetomidine is an ideal anaesthetic agent for catheter ablation of A-fib, although it was not previously validated. In the current trial, both anaesthetic regimens provided adequate levels of sedation and analgesia, enabling uninterrupted and uneventful ablation in all of the patients. However, the combination of dexmedetomidine with low-dose remifentanil showed superior sedative and analgesic effects compared with the midazolam–remifentanil regimen. This finding is consistent with the results of a previous study that compared the sedative effects of dexmedetomidine and midazolam during colonoscopy.8 In current study, dexmedetomidine was also superior in terms of maintaining adequate respiration and the satisfaction of cardiologists. The well-known opioid- and anaesthetic-sparing effects of dexmedetomidine14,22,23 are due to persistent actions on a-2 adrenoceptor in the spinal cord.24 Dexmedetomidine does not cause severe respiratory depression because of its a-2 adrenergic agonistic action but does provide sufficient sedation and analgesia.13 Accordingly, we observed increased sedation and analgesia in the DR group compared with the MR group despite using one-third of the dose of remifentanil. The opioid-sparing effect and ability to maintain spontaneous ventilation may have significantly reduced respiratory depression and heavy breathing, leading to increased satisfaction among cardiologists. However, dexmedetomidine has the potential to cause hypotension due to systemic vasodilation via sympatholytic actions.20 Dexmedetomidine usually elicits a biphasic haemodynamic response with an initial increase in blood pressure and reflex bradycardia followed by a subsequent return to baseline after stabilization.25 Although patients in the DR group showed a trend towards a higher incidence of hypotension compared with those in the MR group (5 vs. 0, P ¼ 0.056), blood pressure was rapidly restored in all patients only if the infusion rate was reduced within the range of the studied dose. Thus, the chosen dose range in the current trial (0.2– 0.7 mg/
Improved sedation with DR compared with MR during catheter ablation of A-fib
Conclusions We found that dexmedetomidine combined with a three-fold lower dosage of remifentanil achieved improved sedation, reduced respiratory depression, and improved satisfaction for cardiologists compared with the combination of midazolam and remifentanil. A trend towards a higher incidence of intra-procedural hypotension was noted in the dexmedetomidine group. However, this was benign and infrequent. Future large-scale studies should be performed in susceptible patients. Dexmedetomidine combined with remifentanil may be an effective and safe anaesthetic regimen during catheter ablation of A-fib.
Acknowledgements Assistance with the study was provided by Hui-Nam Pak, Professor, and Boyoung Joung, Associate Professor, Cardiology Division, Yonsei Cardiovascular Center and Cardiovascular Research Institute, Yonsei University Health System.
Conflict of interest: none declared.
References 1. Cheema A, Vasamreddy CR, Dalal D, Marine JE, Dong J, Henrikson CA et al. Long-term single procedure efficacy of catheter ablation of atrial fibrillation. J Interv Card Electrophysiol 2006;15:145 – 55. 2. Mandel JE, Hutchinson MD, Marchlinski FE. Remifentanil-midazolam sedation provides hemodynamic stability and comfort during epicardial ablation of ventricular tachycardia. J Cardiovasc Electrophysiol 2011;22:464 – 6. 3. Brugada J, Berruezo A, Cuesta A, Osca J, Chueca E, Fosch X et al. Nonsurgical transthoracic epicardial radiofrequency ablation: an alternative in incessant ventricular tachycardia. J Am Coll Cardiol 2003;41:2036 – 43. 4. Mitchell AR, Chalil S, Boodhoo L, Bordoli G, Patel N, Sulke N. Diazepam or midazolam for external DC cardioversion (the DORM Study). Europace 2003;5:391–5. 5. Trentman TL, Fassett SL, Mueller JT, Altemose GT. Airway interventions in the cardiac electrophysiology laboratory: a retrospective review. J Cardiothorac Vasc Anesth 2009;23:841 –5. 6. Kauppila T, Kemppainen P, Tanila H, Pertovaara A. Effect of systemic medetomidine, an alpha 2 adrenoceptor agonist, on experimental pain in humans. Anesthesiology 1991;74:3 –8. 7. Venn RM, Bradshaw CJ, Spencer R, Brealey D, Caudwell E, Naughton C et al. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia 1999;54:1136 –42. 8. Dere K, Sucullu I, Budak ET, Yeyen S, Filiz AI, Ozkan S et al. A comparison of dexmedetomidine versus midazolam for sedation, pain and hemodynamic control, during colonoscopy under conscious sedation. Eur J Anaesthesiol 2010;27:648 – 52. 9. Arain SR, Ruehlow RM, Uhrich TD, Ebert TJ. The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery. Anesth Analg 2004;98:153 –8. 10. Koruk S, Mizrak A, Gul R, Kilic E, Yendi F, Oner U. Dexmedetomidine-ketamine and midazolam-ketamine combinations for sedation in pediatric patients undergoing extracorporeal shock wave lithotripsy: a randomized prospective study. J Anesth 2010;24:858 –63. 11. McCutcheon CA, Orme RM, Scott DA, Davies MJ, McGlade DP. A comparison of dexmedetomidine versus conventional therapy for sedation and hemodynamic control during carotid endarterectomy performed under regional anesthesia. Anesth Analg 2006;102:668 –75. 12. Tosun Z, Akin A, Guler G, Esmaoglu A, Boyaci A. Dexmedetomidine-ketamine and propofol-ketamine combinations for anesthesia in spontaneously breathing pediatric patients undergoing cardiac catheterization. J Cardiothorac Vasc Anesth 2006;20:515 –9. 13. Kunisawa T, Ueno M, Kurosawa A, Nagashima M, Hayashi D, Sasakawa T et al. Dexmedetomidine can stabilize hemodynamics and spare anesthetics before cardiopulmonary bypass. J Anesth 2011;25:818 –22. 14. Al-Zaben KR, Qudaisat IY, Al-Ghanem SM, Massad IM, Al-Mustafa MM, Al-Oweidi AS et al. Intraoperative administration of dexmedetomidine reduces the analgesic requirements for children undergoing hypospadius surgery. Eur J Anaesthesiol 2010;27:247 –52. 15. Wallace S, Mecklenburg B, Hanling S. Profound reduction in sedation and analgesic requirements using extended dexmedetomidine infusions in a patient with an open abdomen. Mil Med 2009;174:1228 –30. 16. Aryana A, Heist EK, D’Avila A, Holmvang G, Chevalier J, Ruskin JN et al. Pain and anatomical locations of radiofrequency ablation as predictors of esophageal temperature rise during pulmonary vein isolation. J Cardiovasc Electrophysiol 2008;19:32–8. 17. Alaeddini J, Wood MA, Parvez B, Pathak V, Wong KA, Ellenbogen KA. Site localization and characterization of pain during radiofrequency ablation of the pulmonary veins. Pacing Clin Electrophysiol 2007;30:1210 – 4. 18. Salukhe TV, Willems S, Drewitz I, Steven D, Hoffmann BA, Heitmann K et al. Propofol sedation administered by cardiologists without assisted ventilation for long cardiac interventions: an assessment of 1000 consecutive patients undergoing atrial fibrillation ablation. Europace 2012;14:325 –30. 19. Pugsley MK. The diverse molecular mechanisms responsible for the actions of opioids on the cardiovascular system. Pharmacol Ther 2012;93:51–75. 20. Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs 2000;59:263 – 70. 21. Tobias JD, Berkenbosch JW. Initial experience with dexmedetomidine in paediatric-aged patients. Paediatr Anaesth 2002;12:171 –5. 22. Carollo DS, Nossaman BD, Ramadhyani U. Dexmedetomidine: a review of clinical applications. Curr Opin Anaesthesiol 2008;21:457–61. 23. Jalonen J, Hynynen M, Kuitunen A, Heikkila H, Perttila J, Salmenpera M et al. Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. Anesthesiology 1997;86:331 –45. 24. Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg 2000;90: 699 –705.
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kg/h) seems to be safe, which is further supported by a study that reported an increase in the relative risk of developing bradycardia and hypotension (requiring treatment) only after administering a loading dose and maintenance dose of .0.7 mg/kg/h in critically ill patients.26 However, caution should be exercised when using a higher dose range as some studies have reported a tendency for dexmedetomidine-treated patients to require perioperative treatment for hypotension and/or bradycardia.14,27,28 Also, the results of the current trial cannot be extrapolated to patients who have compromised cardiac function. There has been concern regarding the potential of dexmedetomidine to delay recovery. One study reported that dexmedetomidine caused prolonged anaesthetic recovery compared with a combination of midazolam and fentanyl in adult patients undergoing extracorporeal shock wave lithotripsy.29 However, in another study, the combination of dexmedetomidine and ketamine reduced recovery time in comparison with the combination of midazolam and ketamine. Recovery time in that study was assessed by eye-opening, verbal responses, and cooperation time in paediatric patients who received the same procedure.13 Despite continuous infusion of dexmedetomidine for 3 –4 h, we did not observe a prolonged recovery time compared with midazolam. This may be due to repeated administration of midazolam, which may have resulted in prolonged sedation and respiratory depression because the active metabolite has a long half-life (1.8 –6.4 h).30 In contrast, dexmedetomidine undergoes nearly complete hepatic metabolism into inactive metabolites. The half-life of dexmedetomidine is 1.5 –3 h after intravenous injection. Therefore, dexmedetomidine may be easier to titrate and promotes faster recovery if used for a prolonged period of time.13 A limitation of this study is that the attending anaesthesiologist was not blinded to the study group. In contrast, the patients and cardiologists were blinded to the group allocation. Continuous infusion of midazolam throughout the procedure just for blinding purposes might cause excessive sedation, severe hypotension, respiratory depression, or even prolonged recovery. Thus, the attending anaesthesiologist inevitably noticed differences in the groups based on the regimens that each received.
1005
1006 25. Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology 1992;77:1134 –42. 26. Tan JA, Ho KM. Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: a meta-analysis. Intensive Care Med 2010;36: 926 –39. 27. Bekker AY, Basile J, Gold M, Riles T, Adelman M, Cuff G et al. Dexmedetomidine for awake carotid endarterectomy: efficacy, hemodynamic profile, and side effects. J Neurosurg Anesthesiol 2004;16:126 –35.
J.S. Cho et al.
28. Talke P, Li J, Jain U, Leung J, Drasner K, Hollenberg M et al. Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. The Study of Perioperative Ischemia Research Group. Anesthesiology 1995;82:620 –33. 29. Zeyneloglu P, Pirat A, Candan S, Kuyumcu S, Tekin I, Arslan G. Dexmedetomidine causes prolonged recovery when compared with midazolam/fentanyl combination in outpatient shock wave lithotripsy. Eur J Anaesthesiol 2008;25:961 –7. 30. Gan TJ. Pharmacokinetic and pharmacodynamic characteristics of medications used for moderate sedation. Clin Pharmacokinet 2006;45:855 –69.
EP CASE EXPRESS
doi:10.1093/europace/eut431 Online publish-ahead-of-print 27 January 2014
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Atrial flutter ablation in a patient with Marfanoid syndrome and anomalous cavotricuspid isthmus Russell Heath, Joseph Kay, and Duy Thai Nguyen* Electrophysiology, Cardiology Division, University of Colorado, Anschutz Medical Campus, 12401 E. 17th Avenue, B-132, Aurora, CO 80045, USA
* Corresponding author. Tel: +1 720 848 0758; fax: +1 720 848 0475, E-mail: [email protected]
The full-length version of this report can be viewed at: http://www. escardio.org/communities/EHRA/publications/ep-case-reports/ Documents/Atrial-flutter-ablation-in-a-patient.pdf.
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An 18-year-old man, with a Marfanoid connective tissue disorder, presented with atrial flutter (Panel C). He was referred for electrophysiology study and ablation. Entrainment manoeuvres confirmed the presence of typical counterclockwise cavotricuspid isthmus (CTI)dependent atrial flutter (Panel D). On intracardiac echocardiography (ICE; AcuNav, Biosense Webster), an enormous pouch was visualized along the medial CTI, near the tricuspid valve, and adjacent to the coronary sinus (Panel A and Video). Using a 3.5 mm Thermocool catheter (Biosense Webster), ablation lateral and medial to the pouch terminated the atrial flutter with bidirectional block (Panel E). A cardiac magnetic resonance imaging (Panel B) showed that the pouch was, in fact, an atrial anastomosis from the right atrial (RA) floor to an anomalous ‘portal’ vein from the liver (arrow). Cardiac manifestations of Marfan’s syndrome include aortic dilation and aneurysmal formation, leading to aortic dissection or rupture. To our knowledge, structural abnormalities of the atrium and venous anomalies have not been described. Only several cases of atrial flutter and Marfan’s syndrome have been reported, and none have defined RA anatomy by ICE. Intracardiac echocardiography was a valuable tool for ablation in this case and should be considered in patients with connective tissue disorders, as they may be predisposed to aberrant cardiac anatomy.
