This prospective, randomized and double-blind clinical research was approved by the Ethics Committee of Fujian Medical University, China (No. 2020KY018). Informed consent was obtained from all patients before the procedure. The study was registered at http:// www.chictr.org.cn (No. ChiCTR2000030969).
We included 64 ASD patients aged ≥ 18 years old, American Society of Anesthesiologists (ASA) physical status < IV and scheduled for percutaneous ASD device (Amplatzer atrial septal occluder) closure under TTE guidance from March 2020 to January 2021. Indications for the procedure included hemodynamically significant left to right shunts, a single secundum ASD without any other intracardiac structural abnormality, sufficient rims, satisfactory transthoracic acoustic windows. The exclusion criteria were as follows: STOP-BANG score ≥ 3, severe renal, heart rate < 60 beats per minute, second- or third-degree block, hepatic, or heart failure, known drug allergies, or a history of drug abuse [10, 11].
The patients were randomly allocated into the dexmedetomidine-remifentanil (D-R) group (n = 32) or the propofol-remifentanil (P-R) group (n = 32) for sedation by a random number table. Among the 64 patients, 2 patients were converted to surgical repair under general anesthesia and 3 patients with poor transthoracic acoustic windows were guided by transesophageal echocardiography (TEE), those patients were excluded from the study. Finally, data for 59 patients (29 patients in the D-R group and 30 patients in the P-R group) were analyzed.
Both the surgeons and patients were blinded to the sedation protocol. None of the patients were premedicated. The sedation level was assessed with the Observer’s Assessment of Alertness/Sedation (OAA/S) scale  and bispectral index score (BIS, Aspect Medical System, Newton, MA, USA). Intraoperative sedation levels were targeted to achieve a BIS of 60–85 and an OAA/S score ≤ 4. Remifentanil (Ultiva®, China National Pharmaceutical Industry Corporation Ltd., HeBei, China) was infused continuously at a rate of 4 µg/kg per hour in both groups before starting the procedure. For the D-R group, the initial infusion of dexmedetomidine (Precedex®, Yangtze River Pharmaceutical (Group) Co. Ltd., JiangSu, China) was set at 6.0 µg/kg/h for 10 minutes as the initial loading dose, followed by a maintenance infusion beginning at a rate of 1.0 µg/ kg/h. In the P-R group, the initial infusion of propofol (Pofol®, B.Braun Melsungen AG, Melsungen, Germany) was set at 6.0 mg/kg/h for 10 minutes, followed by continuous infusion beginning at a rate of 2 mg/kg/h. When target sedation level was obtained, the maintenance infusion rate of sedatives was adjusted according to the patients’ sedation level and all drugs were discontinued at the end of the procedure in both groups.
If sedation level was inadequate in either group, the infusion rates of sedatives were increased at first. Besides, a bolus of 10–20 mg propofol was administered as a rescue sedation therapy when first-line treatment failed .
Anesthesia management and data collection
Vital signs were monitored continuously and recorded at 5-min intervals: oxygen saturation (SpO2), heart rate (HR), electrocardiogram (ECG), respiratory rate (RR). In addition, an arterial catheter was routinely inserted for assessing invasive arterial pressure, and arterial blood gas analysis was performed at baseline (breathing room air). All patients were breathing spontaneously, and 4 L/min oxygen was given through a nasal cannula. The sedation protocols were started after placement of the arterial catheter in both groups. On achieving the targeted sedation level (BIS of 60–85 and an OAA/S score ≤ 4), the right groin was infiltrated with 10 mL of 1% lidocaine at the beginning of the interventional procedure.
Arterial blood gas analysis was repeated immediately after the procedure. The number of patients with hypercapnia (PaCO2 ≥ 45 mmHg) was evaluated. The time needed to achieve an Aldrete score ≥ 9 weas noted . Patients were asked to evaluate their levels of pain (0 = no; 1–3 = mild; 4–6 = moderate; 7–10 = severe pain) by using the visual analogue scale (VAS) and were transferred to the ward when the Aldrete score was ≥ 9 . The satisfaction with the quality of the sedation (5-point Likert scale: 1, very satisfied; 2, satisfied; 3, neutral; 4, dissatisfied; and 5, very dissatisfied) were evaluated by the surgeons and patients .
Hemodynamic and respiratory adverse events were defined as follows. Hypotension (mean arterial blood pressure < 65 mmHg), hypertension (mean arterial blood pressure ≥ 20% of baseline), bradycardia (heart rate < 50 beats per minute), bradypnea (respiratory rate < 8/min for ≥ 1 minute), apnea (absence of ventilator effort ≥ 20 seconds) and oxygen desaturation (SpO2 < 90% for ≥ 10 seconds) were all recorded .
We managed adverse respiratory events with a jaw thrust, mask ventilation, by increasing oxygen flow, or asopharyngeal/ oropharyngeal airway insertion. Noradrenaline, urapidil, atropine, or esmolol was administered for adverse hemodynamic events.
The efficacy of sedation protocols was assessed on the ability to successfully complete the procedure without rescue sedatives, pain score, infusion rate of remifentanil, induction time (the time to achieve targeted levels of sedation), recovery time (the time to an Aldrete score ≥ 9), anesthetic satisfaction of the surgeons and patients. The incidence of hemodynamic and respiratory adverse events, arterial blood gas analysis, hypercapnia all were compared to evaluate the safety of sedation protocols.
Interventional Procedure and Echocardiography Guidance
The patient was placed in a supine position, and TTE was performed continuously throughout the procedure to monitor device deployment. The interventional procedure of percutaneous closure of ASD has been described in the previous study . Briefly, a venous sheath was inserted after the right femoral vein was punctured and systemic heparinization (1 mg/kg) was performed. Subsequently, a catheter was inserted, followed by advancement of a guidewire through the ASD into the left atrium. Then, an occluder was delivered carefully through the sheath. The left disc was deployed in the left atrium and pulled back against the atrial septum, and then the right atrial disc was deployed. Finally, the device was released once the occluder was positioned properly.
If patients did not undergo successful device implantation due to severe residual shunt, complete heart block, or device dislodged, then the patients were referred for surgical repair under general anesthesia with endotracheal intubation as a remedial measure and were excluded from the final sedation analysis.
Statistical analyses were performed by SPSS software (ver.22.0, SPSS Inc., Chicago, IL, United States). The results are presented as the mean ± standard deviation (SD) for the continuous variables and as the numbers or percentages for categorical variables. Continuous and categorical variables were tested by using Student’s t test and χ2 test or Fisher’s exact test, respectively. For comparison of the grade data, Wilcoxon rank- sum test was performed. All statistical tests were two-tailed with a significance level of 0.05.
The main safety concern with sedation in patients is respiratory adverse events. According to a previous study, propofol-remifentanil combinations for sedation during hysteroscopy, the incidence of respiratory depression was 40%. Based on this result, the decreases in the incidence of respiratory depression to 10% in dexmedetomidine-remifentanil group was considered clinically significant . A sample size of 32 subjects per group was required considering a one-sided test with α = 0.025, power of 80%(β = 0.20) and assuming a 10% drop-out rate.