1. Introduction
Every year, millions of patients worldwide undergo various surgical procedures (1). Irrespective of its extent, duration, and type, surgery is invariably an anxiety-provoking and stressful experience for patients (2, 3). Most of surgical procedures are performed under general anesthesia (4). Complications of general anesthesia include a protracted postoperative recovery period, agitation, and restlessness (5). Post-anesthesia agitation and restlessness are significant concerns for medical staff (6). Agitation is a clinical condition accompanied by restlessness, confusion, and aggressive behavior in the initial phase of recovery from general anesthesia. During periods of agitation, patients may experience disturbances in awareness and consciousness, disorientation, heightened sensory sensitivity, and increased motor activity. While this situation may impose self-limiting constraints, it can also cause physical harm to the patient, particularly in the surgical area (7). Agitation can also occur acutely, which is considered a behavioral disorder in the early postoperative period (8). This common complication after general anesthesia is characterized by various manifestations including crying, agitation, limb thrashing and movement, wandering, and can increase serious injuries such as extubation, falling from the bed, accidental removal of surgical dressings, and dislodgement of intravenous catheters and drains (9). Agitation in a patient can lead to serious consequences including respiratory depression, nausea and vomiting, increased blood pressure, increased heart rate, and increased myocardial oxygen consumption (10), Furthermore, agitation may also trigger stress responses, delay surgical wound healing, and suppress the immune system after surgery (8).
Although agitation manifests differently in various individuals, aimless limb movements and pounding, restlessness, and wandering typically appear in patients. Furthermore, patients often respond poorly to verbal commands (11). The actual incidence and risk factors of agitation are unknown. In adult non-cardiac surgeries, the incidence of agitation has been documented to be approximately 19% (12). A multitude of factors have been identified as potential etiological agents of agitation in patients, including metabolic disorders, nervousness, previous surgery, patient adaptability, pain, and the duration of anesthesia (13).
Agitation is a prevalent complication in 63.5% of patients after abdominal surgery, which is associated with increased postoperative complications and hospitalization costs (14). This clinical complication requires additional nursing care and supplementary sedatives or analgesics, which can also cause respiratory depression (9). Nurse-patient communication and providing information about the condition and treatment process are considered methods of reducing patient stress and anxiety (15).
Severe agitation can be dangerous and lead to patient-ventilator asynchrony, increased oxygen consumption, and inadvertent dislodgement of devices and catheters connected to the patient (16). These issues are related to the individual's recovery time after surgery, length of hospital stay, patient costs, and healthcare staff satisfaction (17). Research findings that recovery duration and emergence from anesthesia a significant role in clinical outcomes, treatment costs, and surgical results (18). A persistent concern for anesthesiologists from the past until now has been the delay in recovery from anesthesia and determining the patient's level of consciousness. A variety of factors influence the recovery process from anesthesia and the attainment of consciousness. These factors include patient-related factors, medications, anesthetics, and surgical interventions. Researchers have made significant efforts to find therapeutic solutions for patients recovering from anesthesia (19). Consequently, various programs have been developed and implemented worldwide to reduce patients ‘recovery time after surgery (17).
One of these methods is sensory stimulation. Sensory stimulation is a therapeutic method that enhances cognitive function by activating the reticular activating system (RAS); it also creates collateral relationships that help reorganize brain activity, leading to increased RAS activity and arousal. These stimulations can include visual, olfactory, tactile, gustatory, and auditory stimulations (19).
Research has shown that auditory stimulation is an easy, inexpensive, and noninvasive tool for reducing patient anxiety (20). Dehghani et al.'s study showed that auditory stimulation with familiar sounds improved patients ‘consciousness scores after rhinoplasty surgery. Auditory stimulation increases wakefulness in individuals by reorganizing brain activity and affecting the reticular activating system. It also reduces the recovery time from anesthesia in patients (19). Lee et al. showed that after minimally invasive abdominal surgery, the use of auditory reminders by the anesthesia team significantly reduced patient agitation (14). Hearing is crucial for experiencing peace and security. Furthermore, it is typically the last sense to fade in patients with diminished consciousness. Auditory stimulation is the easiest type of stimulation in patient care; which nurses can easily provide it through verbal communication during care activities, and it is applicable to a large number of patients.
A literature review found that several studies on auditory stimulation during recovery have been conducted, and in some cases, the anesthesia team provided this stimulation. However, in the operating room after the surgery ends and during the awakening phase, patient restlessness is higher, and the effect of familiar sounds on patient awareness is significant.
Given the potential benefits of familiar sensory stimuli in reducing patient agitation and improving recovery, as well as the adverse consequences of restlessness and agitation during the recovery period following general anesthesia, the present study was conducted to determine the effect of nurse voice-based auditory orientation on postoperative agitation and recovery time in patients undergoing laparoscopic cholecystectomy (LC).
2. Materials and Methods
2.1 Study Population and Setting
This randomized clinical trial (RCT) was conducted at Imam Reza and Ghaem hospitals, affiliated to Mashhad University of Medical Sciences, Mashhad, Iran from May 2024 through January 2025. For this purpose, we asked 54 consecutive patients eligible for LC to participate in the study.
2.2 Inclusion and Exclusion Criteria
Participants were eligible for this study if they met the following criteria:
The eligibility criteria included having informed consent to participate in the study, awareness of time and place, the age range of 18-70 years, body mass index (BMI˂30 kg/m2), patient’s first surgical experience and meeting the American Society of Anesthesiologists Physical Status (ASAPS) classification I-II were the inclusion criteria of the study.  Moreover, pregnancy at the time of surgery, which required upper abdominal surgery procedures like adhesiolysis, a history of anesthesia or sedation within the past month, hearing impairment, cognitive disorders (e.g., Alzheimer's disease, dementia, or memory impairment), substance or psychotropic drug use disorder, history of addiction, a history of mental illness, and the use of antipsychotic medications were considered as the pre-operative exclusion criteria of the study. In addition, intraoperative exclusion criteria included conversion from laparoscopic to open surgery, prolonged operation time lasting more than 2 h, drain insertion, and iatrogenic perforation. Furthermore, we registered the study in the Iranian Registry of Clinical Trials (IRCT) (protocol number: IRCT20240529061947N1).
2.3 Study Design and Randomization
The required sample size for the present study was determined based on the findings of Lee et al. (19). Using G*Power software, with a statistical power of 0.95 and a significance level (α) of 0.05, and accounting for an anticipated 20% dropout rate, the required sample size was calculated as 27 participants per group.
Therefore, these individuals were randomly categorized into control and intervention groups with the permuted blocks (viz. 10 blocks: 5 blocks from Imam Reza Hospital and 5 blocks from Ghaem Hospital) in the form of random allocation (using the Random Allocation Software). Finally, 54 consecutive patients as candidates for CL were randomly allocated to one of the following two groups; 27 cases were assigned to the intervention group (Group I) who received awareness with auditory sensory stimulation was conducted using the pre-recorded voice of the patient's nurse from the surgical ward; and 27 patients were entered into Group II with no intervention, merely serving as the control group of the study.
2.4 Data Collection
Before data collection, the study objectives and procedures were explained to the patients, and written informed consent was obtained from those who voluntarily agreed to participate. The researchers then addressed any questions or concerns raised by the participants. Demographic and clinical data were collected through face-to-face interviews, review of medical records, and physical measurements. All baseline data were recorded within 24 hours before surgery. Patients were assessed on the evening before surgery, prior to the administration of anesthesia.
2.5 Anesthetic Methods
Once in the operating room, patients were placed under standard monitoring, including an electrocardiogram, pulse oximetry, blood pressure, and an end-tidal carbon dioxide measurement probe. The anesthetists followed a standardized protocol. General anesthesia was induced on all patients under the supervision of the anesthesiologist with intravenous fentanyl (2 µg/kg), propofol (2 mg/kg), and atracurium (0.5 mg/kg). The patient was then intubated with an appropriate endotracheal tube and placed on mechanical ventilation. Oxygen (O₂) 50%, nitrogen dioxide (NO₂) 50%, and 1 MAC (Minimum Alveolar Concentration) isoflurane were used for maintenance, and the ventilation frequency was adjusted to maintain end-tidal CO₂ partial pressure from 30 to 35 mmHg. Anesthesia was maintained with isoflurane 0.5% and remifentanil infusion 0.05-0.2 µg/kg, and atracurium besylate 10 mg every 30 minutes as needed. To reverse the effects of muscle relaxants was used, neostigmine 0.04 mg/kg and atropine 0.02 mg/kg, along with ondansetron 4 mg for prophylaxis to prevent nausea and vomiting.
All laparoscopic procedures were performed by the same surgeon at Imam Reza and Ghaem Hospitals, Iran. In addition, laparoscopic port (or trocar) placement was determined based on the patients’ needs and condition, and laparoscopic access was provided using a standard three-port method. Furthermore, laparoscopy was accomplished with CO₂ as the distending medium. We also monitored intra- abdominal gas pressure and the total volume of the gas delivered during the course of laparoscopy. Consequently, CO₂ was insufflated via an umbilical port with the pressure of 8-10 mmHg (note: CO₂ pressure was adjusted to 12 mmHg during laparoscopy). Finally, two 5-mm trocars were inserted into the left iliac fossa and the suprapubic region. Before removing the trocars, the carbon dioxide pneumoperitoneum was systematically evacuated. It is noteworthy that the surgeon, the anesthetists, and the data collectors were blinded to the study.
After the surgeon had finished the operation and the administration of reversal medications began, the intervention started with the anesthesiologist's permission. At this stage, after the operation was finished and before the patient was transferred to the recovery room, patients in the intervention group received auditory sensory stimulation through headphones via a nurse's voice to promote awareness. In this study, patients in both the intervention and the control groups used BOROFONE wireless headphones (Model BO11), manufactured in China.
2.6 The auditory sensory stimulation with the nurse's voice
To prepare familiar voices, the researcher collaborated with the nurse responsible for the patient's care, who had performed all pre-operative care for the patient in the surgical ward, so their voices could be recorded using the desired text. In order to standardize the voices and to eliminate potential errors caused by the influence of male or female voices, only female nurses were considered in the study. For all patients in the intervention group, the following text was played over the nurse's voice:
'Sir/ Madam. ... I am your nurse. You are waking up from anesthesia. Your surgery has been successfully completed. You are fine, don't worry. You are in the operating room at ... Hospital. Please open your eyes."
This sound was played repeatedly through headphones at a normal hearing intensity of 50 to 60 decibels; from the time the anesthetic was discontinued until the patient had sufficient respiratory function and cooperation to be extubated and open their eyes. Patients in the control group received routine care administered as usual in the operating room. To minimize bias, and because of extraneous sounds in the operating room—such as device alarms, equipment movement, staff conversations, and door openings/closings—could influence patient agitation, we controlled for them by using headphones in the control group. This eliminated this confounding variable and ensured consistent conditions across groups. However, the patients in the control group only heard the following sentence:
'Sir/Madam …, open your eyes. The surgical procedure has been completed.'
After airway secretions were suctioned, patients in both groups who demonstrated adequate respiratory function and cooperation, and were deemed fit for extubation by the anesthesiologist, were transferred to the recovery room for monitoring and oxygen therapy.
2.7 Outcomes
The assessment of patient agitation used the Richmond Agitation-Sedation Scale (RASS), which consists of 10 levels: four levels indicating agitation, one level representing a calm and alert state, and five levels indicating increasing levels of sedation. The Richmond Scale was developed and validated by Sessler et al. (21). In Iran, it was translated and validated by Tadrissi et al. in 2009, with an inter-rater reliability reported as an intraclass correlation coefficient (ICC) of 0.95 (22). In this study, agitation scores were recorded in both groups at the following time points: before auditory stimulation, at the time of extubation, five 5 minutes post-extubation, upon entry into the recovery room, and then every 10 minutes during the first 30 minutes of recovery. The Aldrete Score checklist was used to evaluate the patient's clinical status in the post-anesthesia care unit. The evaluation encompassed five parameters: level of consciousness, respiration, motor function, hemodynamic stability, and arterial oxygen saturation (23).  In the present study, we recorded the recovery time (in minutes) for both groups using the validated Aldrete Score checklist, a widely accepted tool for evaluating the recovery process in medical settings.
2.8 Statistical Analysis
Mean ± standard deviation (SD) or median (interquartile range) for continuous variables and frequencies (%) for categorical variables were used to show baseline characteristics of the participants. To compare demographic characteristics between the intervention and control groups, we used the Chi-square test or Fisher’s exact test for qualitative variables, and the independent t-test was used for quantitative variables. However, because the assumptions of t-test were not met when comparing recovery time between the two groups, we used the non-parametric equivalent, the Mann–Whitney U test. Given that agitation scores were measured and recorded at seven different time points for each patient in both groups, the Generalized Estimating Equations (GEE) method was used for comparison. For each statistical analysis, a p-value < 0.05 was considered significant. The data analysis was performed using the SPSS (version 22) software (SPSS Inc. Chicago; IL: USA).
3. Result
The mean age of patients in the intervention group was 46.41 ± 14.28 years, and in the control group, it was 43.89 ± 11.69 years (P = 0.48). The mean body mass index (BMI) was 26.93 ± 3.28 in the intervention group and 26.93 ± 3.28 in the control group (P = 0.82). The independent t-test revealed that there were no statistically significant differences between the two groups in terms of age or BMI (P > 0.05). The Chi-square test or Fisher’s exact test showed no statistically significant differences between the two groups with regard to gender, education level, history of underlying diseases, marital status, or history of smoking (P > 0.05) (Table 1).
Statistical analysis showed no significant differences between the two groups with regard to the duration of mechanical ventilation, the duration of surgery, or time to extubation (P > 0.05).
However, recovery time differed significantly between the groups (P < 0.01).  The intervention group demonstrated a considerably reduced recovery time. (Table 2). The results showed that the control group had higher mean scores in the recovery time variable, as demonstrated in the box plot (Figure 1).