Evaluation of the analgesic efficacy of dinalbuphine sebacate in transoral robotic surgery for obstructive sleep apnea–hypopnea syndrome: a single-center retrospective cohort study

Abstract

Obstructive sleep apnea–hypopnea syndrome (OSAHS) is a chronic disorder with significant comorbidities. Transoral robotic surgery (TORS) combined with uvulopalatopharyngoplasty (UPPP) is an established treatment, but postoperative pain management remains challenging. This study evaluates the efficacy of dinalbuphine sebacate (DNS), an extended-release analgesic, in reducing opioid use and managing postoperative pain in TORS UPPP patients. This retrospective cohort included consecutive TORS-UPPP patients from 1 January 2020 to 30 June 2024; the database was locked on 30 June 2024 prior to analysis. The patients were divided into a DNS group (n = 96) and a conventional analgesia (CA) group (n = 42). The DNS group received a 150 mg intramuscular injection after anesthetic induction and after the surgery. Analgesic consumption, opioid usage, and pain scores were evaluated from the day of surgery (POD0) to two days postoperatively (POD2), as well as opioid prescriptions at discharge and during the first follow-up. The DNS group exhibited a significantly lower percentage of opioid use during POD0–POD2 (30.21% vs. 54.76%, p < 0.001) and a reduced oral morphine equivalent dose (15.31 ± 36.68 mg vs. 56.79 ± 85.83 mg, p = 0.001). Opioid prescriptions at discharge (68.75% vs. 88.10%, p = 0.016) and at the first follow-up (13.54% vs. 52.38%, p < 0.001) were also lower in the DNS group, with comparable analgesic effects. DNS effectively reduces postoperative opioid consumption and prescription in TORS UPPP patients without significant adverse effects. These findings support the integration of DNS into multimodal analgesia protocols for OSAHS surgery, substantially reduced inpatient and post-discharge opioid use (NNT ≈ 3–5) with small, likely non-clinically important differences in pain scores and no significant safety signal, supporting its clinical relevance in OSAHS surgical programs. Warranting further multicenter validation.

Supplementary Information

The online version contains supplementary material available at 10.1007/s11701-025-02829-w.

Introduction

Obstructive sleep apnea–hypopnea syndrome (OSAHS) is a chronic airway-related disorder linked to significant comorbidities individually, including cardiovascular disease, metabolic syndrome, and neuropsychiatric dysfunction. Beyond the personal outcomes, OSAHS imposes a substantial and heterogeneous burden globally, with high prevalence across regions and far‑reaching health and socioeconomic consequences; recent syntheses highlight underdiagnosis, elevated accident risk, and increased healthcare utilization, underscoring OSA as a public‑health priority [1]. In the United States alone, undiagnosed OSA was estimated to cost ~ $149.6 billion (2015), with productivity losses accounting for the largest share, alongside motor-vehicle and workplace accidents and higher healthcare utilization; treatment is associated with improved attendance and on-the-job productivity [2].Among OSAHS patients with surgically correctable upper-airway anatomical abnormalities, interventions including tonsillectomy, uvulopalatopharyngoplasty (UPPP), and radiofrequency for base of tongue (RFBOT) are considered with effective therapeutic options before when applied to carefully selected cases [3].

Transoral robotic surgery (TORS) combined with UPPP—approved by the U.S. Food and Drug Administration (FDA) in 2009 for the treatment of OSAHS—represents an advanced surgical technique designed to reduce tongue base volume and expand the oropharyngeal and hypopharyngeal airways. This approach, often performed with supraglottoplasty, has been shown to significantly improve the apnea–hypopnea index (AHI) and Epworth sleepiness scale (ESS), with reductions averaging 58% in previous studies [4, 5].

Despite its proven efficacy, TORS is frequently associated with severe postoperative pain and dysphagia, which can hinder recovery and adversely affect patient comfort. Postoperative pain may last up to three weeks [6]. Severe cases may result in complications such as dehydration, with uncontrolled pain or dehydration necessitating readmission in 3.3–9.6% of patients undergoing TORS [7, 8]. These findings highlight the critical importance of effective postoperative pain management in this population.

Opioids are commonly used for postoperative pain control; however, their use in OSAHS patients presents unique challenges due to a high incidence of opioid-induced respiratory depression (47.0–84.3%), particularly in opioid-naïve or sleep-disordered individuals [9]. This predisposition increases the risk of postoperative pulmonary complications. Moreover, patients undergoing OSAHS surgery are at risk of excessive opioid prescribing, which can lead to prolonged or inappropriate opioid use, especially among opioid-naïve individuals who receive perioperative opioid prescriptions [10, 11]. Recognizing these risks, the American Society of Anesthesiologists (ASA) has recommended minimizing or eliminating systemic opioid use in the perioperative management of OSA patients in 2018 [12]. Similarly, in 2021, the American Academy of Otolaryngology-Head and Neck Surgery (AAOHNS) emphasized prioritizing non-opioid analgesics for postoperative pain management in otolaryngologic surgeries. The AAOHNS also recommended evaluating patients for opioid misuse risk factors preoperatively [13]. These guidelines underscore the growing consensus among anesthesiologists and otolaryngologists to reduce opioid use in the postoperative care of patients undergoing UPPP.

Dinalbuphine sebacate (DNS, Naldebain®) is an extended-release formulation and prodrug of nalbuphine developed for a single-dose intramuscular injection. After injection into the gluteus maximus, DNS is gradually released into the plasma and rapidly converted into nalbuphine, with a mean absorption time of 145.2 h [14]. This prolonged release provides a long-lasting analgesic effect, rendering DNS a promising option for postoperative pain management since its approval by the Taiwan FDA in 2017. Clinical studies have demonstrated its efficacy in reducing the score relative to the pain numeric rating scale (NRS) and opioid consumption [15, 16]. Additionally, the Taiwan Society of Anesthesiologists’ expert consensus supports incorporating DNS into multimodal analgesia (MMA) strategies to optimize postoperative pain control [17]. Effective pain management strategies that combine analgesics with different pharmacological mechanisms during the perioperative and inpatient periods can significantly reduce postoperative pain and opioid consumption in TORS patients [18, 19].

At our institution, TORS UPPP with the Da Vinci system has been employed for the treatment of OSAHS since 2016. DNS has been integrated into MMA strategies for this patient population since 2020. This study aims to retrospectively evaluate whether the perioperative and inpatient use of DNS in TORS UPPP for OSAHS patients can reduce postoperative opioid consumption and requirement, effectively alleviate postoperative pain, and decrease postoperative complications. By addressing these objectives, this study seeks to contribute to the development of safer and more effective pain management protocols for OSAHS patients undergoing TORS UPPP.

Patients with OSA/OSAHS are vulnerable to opioid-related ventilatory impairment, and major perioperative guidelines recommend multimodal, opioid-sparing strategies with careful dosing and postoperative monitoring. These include the American Society of Anesthesiologists (ASA) practice guideline for perioperative management of OSA and the Society of Anesthesia and Sleep Medicine (SASM) intraoperative guideline, which collectively advocate preferential non-opioid analgesics, minimization of systemic opioids, and risk-adapted surveillance [20]. In otolaryngology, the AAO-HNSF opioid prescribing guideline likewise emphasizes multimodal analgesia and judicious opioid use across common procedures [21]. Within TORS programs, enhanced-recovery protocols have demonstrated reductions in postoperative opioid consumption and pain scores, reinforcing the value of opioid stewardship in this setting [19]. This framework provides the rationale to evaluate whether a DNS-anchored multimodal regimen can reduce inpatient opioid requirements and opioid prescribing after TORS-UPPP.

Materials and methods

This retrospective, single-center, comparative cohort study was designed to evaluate the clinical efficacy of DNS compared to conventional analgesic strategies in postoperative pain management following UPPP. The study adhered to the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of the affiliated hospital (IRB number: CS1-24,073). The study content and format comply with the combined STROBE checklist [22]. We retrospectively analyzed patients diagnosed with OSAHS who underwent TORS UPPP using the Da Vinci system (Intuitive Surgical, Sunnyvale, CA, USA) at our center from 1 January 2020 to 30 June 2024. Data were censored at 30 June 2024 (database lock), and analyses were performed thereafter; the study was approved by the IRB (CS1-24,073, waiver of consent).

The inclusion of these dates was based on the introduction of DNS into the otolaryngology department of our hospital in January 2020. Patients were eligible for inclusion if they had a confirmed diagnosis of OSAHS and a documented record of undergoing TORS UPPP. The exclusion criteria were as follows: (1) preoperative diagnosis of substance abuse, defined as the excessive use of illicit drugs or prescription pain medication; (2) documented history of psychiatric disorders, including depression or anxiety; (3) chronic pain disorder; and (4) diagnosis of dementia. The intervention group was defined as patients who received a complete two-dose regimen of DNS; therefore, patients who only received a single dose were also excluded. A total of 138 patients were included; 96 patients were categorized in the DNS group, and 42 patients were included in the conventional analgesia (CA) group. The patient inclusion and exclusion flowchart is detailed in Fig. 1.

Fig. 1.

Flow diagram of this study

Procedures

All patients underwent general anesthesia with endotracheal intubation, which was maintained with volatile anesthetics. Two otolaryngologists performed all surgical procedures. Patients were divided into two groups based on the use of DNS. Patients in the DNS group received a single 150 mg intramuscular injection of DNS immediately after anesthetic induction, followed by a second 150 mg injection 5–7 days postoperatively. Both injections were guided via ultrasound and administered into the gluteus maximus in order to ensure accuracy and safety. The patients in the CA group did not receive DNS during or after surgery; instead, they were managed with other standard analgesic strategies as determined by the anesthesiologist. After surgery, all patients were monitored in the post-anesthesia care unit (PACU) for 1–2 h and received appropriate analgesics as determined by the anesthesiologist. Patients were transferred to the ward when their Aldrete score reached ≥ 9.

Postoperatively, patients experiencing pain in the ward were managed with analgesics other than DNS based on the physician’s discretion and the patient’s preference. Pain intensity was assessed immediately upon return to the ward and subsequently at fixed times (05:00, 13:00, and 21:00) by the ward primary care nurse using a standard numeric rating scale (NRS, 0–10); In this study, postoperative pain was assessed using the Numeric Rating Scale (NRS), ranging from 0 to 10, where 0 indicated no pain and 10 represented the worst imaginable pain. Pain assessment was considered the “fifth vital sign” and was recorded by nursing staff together with routine vital signs after the patient returned to the ward. Standard assessment time points included immediately upon return to the ward and at 05:00, 13:00, and 21:00 each day. The assessment was conducted verbally by the nurse, asking: “If 10 represents the worst possible pain and 0 represents no pain, what is your current pain score?” The patient’s response was directly documented in the nursing records. These results were recorded in the electronic medical record (EMR). Pain assessments did not differentiate between swallowing pain and resting pain. Patients reporting nausea or vomiting during hospitalization were treated with parenteral prochlorperazine or metoclopramide depending on the situation. Following adequate pain control and wound evaluation, patients were prescribed oral analgesics and discharged. Patients were educated to seek emergency care if they experienced postoperative discomfort.

Data collection

All data were obtained from the hospital’s EMR system, which includes anesthesia records, surgical records, inpatient care records, and outpatient follow-up records. The system undergoes regular internal review and incorporates error correction mechanisms to ensure data completeness and accuracy. Demographic characteristics, including age, gender, height, weight, body mass index (BMI), ASA classification, and surgical time, were recorded. The types and dosages of analgesics administered intraoperatively in the PACU, during the inpatient period, and during outpatient follow-up were thoroughly analyzed based on EMR data.

Analgesic and antiemetic types and dosages administered intraoperatively, on the day of surgery, and during the first two postoperative days were retrieved from the EMR and analyzed in detail. Opioid medications were converted to oral morphine equivalent (OME) doses following the conversion tables provided by the European Society of Anaesthesiology and Intensive Care [23] (see Supplementary Materials S1). Discharge prescriptions were examined to determine whether opioids were prescribed. Opioid use was defined as the prescription of morphine, tramadol, or other opioid analgesics recorded in the EMR. Outpatient follow-up records were reviewed for postoperative opioid prescriptions.

Pain intensity was assessed on the ward using an 11-point NRS at fixed time points and recorded as part of routine vital signs during the period of in-hospital. While outpatient NRS at the first clinic follow-up is not documented in a standardized fashion in our EMR; therefore, so we used opioid prescribing at that visit as a consistent post-discharge outcome.

For patients readmitted to the emergency department (ED), detailed records were reviewed to determine the reason for admission. Pain-related readmissions were defined as cases where analgesics were administered in the ER. Bleeding-related readmissions were defined as cases requiring hemostatic intervention, and dizziness-related readmissions were defined as cases requiring antiemetic administration.

Perioperative analgesic pathway and agents by phase for DNS vs conventional analgesia (CA). The flow diagram of figure 2 displays standardized phases—Counseling/Allocation, Induction, Intraoperative, PACU, Inpatient (POD0–2), and Discharge/1st Follow‑up—for the DNS and conventional analgesia (CA) cohorts. The DNS cohort received 150 mg IM at induction with a scheduled second 150 mg IM on POD5–7, within a multimodal regimen. Both cohorts received perioperative non‑opioid agents with rescue short‑acting opioids as needed. This figure corresponds to the Dosage section; quantitative details (consumption/OME, outcomes) appear in Merged Table 1 and Table 4

Fig. 2.

Perioperative analgesic pathway and agents by phase for DNS vs conventional analgesia (CA)

Table 1.

Patient characteristics and demographics

	DNS group (n = 96)	CA group (n = 42)	p value
Age (years old)	39.81 ± 9.7	43.10 ± 12.4	0.13
Gender			0.02
Male	79 (82.3%)	27 (64.3%)
Female	17 (17.7%)	15 (35.7%)
Height (cm)	170.11 ± 7.13	166.50 ± 7.97
Weight (kg)	84.36 ± 17.86	77.38 ± 16.56
Body mass index	29.09 ± 5.56	27.91 ± 5.91	0.11
ASA classification			0.17
I	14 (14.6%)	2 (4.8%)
II	69 (71.9%)	36 (85.7%)
III	13 (13.5%)	4 (9.5%)
Surgical time (min)	84.88 ± 17.72	104.21 ± 41.44	0.04

Table 4.

Intraoperative analgesic consumption

Phase/outcome	DNS (n = 96)	CA (n = 42)	p value
NRS — when returned to ward	2.38 ± 1.52	2.52 ± 1.76	0.75
NRS — POD1 mean	1.73 ± 0.73	1.41 ± 0.76	0.02
NRS — POD2 mean	1.62 ± 0.71	1.34 ± 0.79	0.03
Antiemetic prescription (inpatient)	19 (19.79%)	11 (26.19%)	0.40
ED readmission — any	13 (13.54%)	9 (21.43%)	0.24
ED readmission — pain‑related	5 (5.21%)	4 (9.52%)	0.46
ED readmission — bleeding‑related	9 (9.38%)	8 (19.05%)	0.11
ED readmission — nausea‑related	0 (0.00%)	0 (0.00%)	N/A
Rehospitalization (any)	0 (0.00%)	2 (4.76%)	0.09

One patient in the DNS group had missing data for volatile agent usage

This missing case was excluded from the statistical analysis

NRS Numeric rating scale, ED Emergency department

Study endpoints

Primary endpoints included the proportion of patients requiring opioids for pain management in the general ward on the day of surgery (POD 0) and the first two postoperative days (POD1 and POD2); OME doses; and the proportion of patients prescribed opioids upon discharge and during the first outpatient follow-up. Secondary endpoints included intraoperative OME doses, PACU OME doses, NRS scores on POD 0–2, the proportion of patients receiving antiemetics during hospitalization, ER readmission rates, and rehospitalization rates.

Statistical analysis

Continuous variables are presented as mean ± standard deviation, and categorical variables are presented as numbers (percentages). Statistical analyses were performed using SAS (SAS ® Enterprise Guide ® 8.4 version). Continuous variables, such as OME doses, were tested for normality using the Shapiro–Wilk test. Data following a normal distribution were analyzed using an independent t-test, while non-normally distributed data were analyzed using the Mann–Whitney U test. Categorical variables, such as the proportion of patients requiring opioids within three postoperative days, were analyzed using chi-square or Fisher’s exact tests, depending on the expected values in the contingency table. Missing NRS data were handled using mean imputation. For potential confounding factors, multivariable logistic regression models were employed to assess the true effect of DNS and control for confounding factors. A p-value < 0.05 was considered statistically significant.

Results

Patient characteristics

A total of 138 patients were included, with 96 in the DNS group and 42 in the CA group (Table 1). The mean age was 40.81 years old, with no significant difference between the DNS and CA groups (39.81 ± 9.70 vs. 43.10 ± 12.40; p = 0.133). Similarly, the mean BMI was 28.73, with no significant difference between the DNS group (29.09 ± 5.56) and the CA group (27.91 ± 5.91; p = 0.113). The mean surgical time was 90.76 min; the DNS group had significantly shorter surgical times (84.88 ± 17.72) than the CA group (104.21 ± 41.44; p = 0.040). The sex distribution (male: 82.3% vs. 64.3%, p = 0.021) was male-dominant in the DNS group, and the ASA classification was comparable between the groups.

Primary outcomes

Postoperative analgesic consumption between the DNS and CA groups

Postoperative analgesic usage relative to POD 0, POD 1, and POD 2 is summarized in Table 2. The use of parenteral tramadol was higher in the CA group (161.90 ± 296.28 mg) than in the DNS group (51.04 ± 122.25 mg; p = 0.412). Similarly, oral tramadol consumption was significantly higher in the CA group (82.14 ± 140.61 mg vs. 0.00 ± 0.00 mg; p < 0.001). Regarding non-opioid analgesics, the CA group consumed significantly more acetylsalicylate (773.81 ± 1668.22 mg vs. 281.25 ± 1048.34 mg; p = 0.005), acetaminophen (711.90 ± 1218.66 mg vs. 0.00 ± 0.00 mg; p < 0.001), and celecoxib (61.90 ± 227.34 mg vs. 0.00 ± 0.00 mg; p = 0.009). In contrast, parecoxib consumption was significantly higher in the DNS group (137.92 ± 67.65 mg) than in the CA group (78.10 ± 86.09 mg; p < 0.001), necessitating post hoc analysis to evaluate its potential confounding effect on the observed outcomes. Opioid usage differed significantly between the groups, with 30.21% of the DNS group using opioids postoperatively compared to 54.76% in the CA group (p < 0.001). Additionally, the OME doses were significantly lower in the DNS group (15.31 ± 36.68 mg vs. 56.79 ± 85.83 mg; p = 0.001).

Table 2.

Postoperative analgesic consumption from the operation day to postoperative day 2

Phase/outcome	DNS (n = 96)	CA (n = 42)	p value
Intraoperative — OME (mg)	40.74 ± 11.61	40.10 ± 11.36	0.75
Intraoperative — Fentanyl (mcg)	176.82 ± 61.37	161.90 ± 47.57	0.24
Intraoperative — Morphine (mg)	1.79 ± 2.79	2.57 ± 3.25	0.21
Intraoperative — Parecoxib (mg)	30.88 ± 16.83	25.71 ± 19.40	0.11
Intraoperative — Ketorolac (mg)	0.62 ± 4.31	2.86 ± 8.91	0.05
Intraoperative — Propacetamol (mg)	62.50 ± 349.81	47.62 ± 308.61	0.82
Intraoperative — Volatile agent: Desflurane	90 (93.75%)	35 (83.33%)	0.05*
Intraoperative — Volatile agent: Sevoflurane	5 (5.21%)	7 (16.67%)
PACU — OME (mg)	3.13 ± 5.99	1.31 ± 4.29	0.04
PACU — Opioid usage (yes)	24 (25.0%)	4 (9.5%)	0.06
PACU — Fentanyl (mcg)	14.06 ± 28.75	6.54 ± 21.42	0.08
PACU — Morphine (mg)	0.05 ± 0.51	0.00 ± 0.00	0.52
PACU — Nalbuphine (mg)	1.04 ± 3.32	0.60 ± 1.98	0.80
PACU — Ketorolac (mg)	0.63 ± 4.30	2.86 ± 8.91	0.05
PACU — Parenteral tramadol (mg)	0.52 ± 5.10	0.00 ± 0.00	0.52
Inpatient (POD0–2) — OME (mg)	15.31 ± 36.68	56.79 ± 85.83	0.001
Inpatient (POD0–2) — Opioid usage (yes)	29 (30.21%)	23 (54.76%)	< 0.001
Inpatient (POD0–2) — Parenteral tramadol (mg)	51.04 ± 122.25	161.90 ± 296.28	0.42
Inpatient (POD0–2) — Oral tramadol (mg)	0.00 ± 0.00	82.14 ± 140.61	< 0.001
Inpatient (POD0–2) — Nalbuphine (mg)	0.31 ± 3.06	0.00 ± 0.00	0.52
Inpatient (POD0–2) — Parecoxib (mg)	137.92 ± 67.65	78.10 ± 86.09	< 0.001
Inpatient (POD0–2) — Ketorolac (mg)	0.00 ± 0.00	5.00 ± 32.40	0.14
Inpatient (POD0–2) — Acetylsalicylate (mg)	281.25 ± 1048.34	773.81 ± 1668.22	0.005
Inpatient (POD0–2) — Oral acetaminophen (mg)	0.00 ± 0.00	711.90 ± 1218.66	< 0.001
Inpatient (POD0–2) — Oral celecoxib (mg)	0.00 ± 0.00	61.90 ± 227.34	0.009

OME values are expressed as mg oral morphine equivalents (means ± SD unless otherwise specified)

Conversion factors are provided in Supplementary Table S1

Phase definitions: intraoperative (induction to emergence), PACU (immediate postoperative care), inpatient POD0–2 (ward)

One patient in the DNS group lacked volatile-agent data and was excluded from that specific comparison

Opioid prescription between the DNS and the CA group

Table 3 compares opioid prescription rates between the DNS and CA groups at discharge and during the first outpatient follow-up. At discharge, opioid prescriptions were lower in the DNS group (68.75%) than in the CA group (88.10%; p = 0.016). During the first outpatient follow-up, the difference increased, with only 13.54% of the DNS group pre-scribed opioids compared to 52.38% relative to the CA group (p < 0.001).

Table 3.

Opioid prescription conditions

Phase/outcome	DNS (n = 96)	CA (n = 42)	p value
Inpatient opioid prescription (any)	29 (30.21%)	23 (54.76%)	< 0.001
Opioid prescription at discharge (any)	66 (68.75%)	37 (88.10%)	0.016
Opioid prescription at first outpatient follow‑up (any)	13 (13.54%)	22 (52.38%)	< 0.001

Secondary outcomes

Intraoperative and PACU analgesia between the DNS and CA groups

The consumption of intraoperative analgesics (Table 2) was analyzed between the two groups. No statistically significant differences were observed in intraoperative opioid and adjunct analgesic consumption. The DNS group demonstrated an average OME dose of 40.74 ± 11.61 mg, which was comparable to the CA group’s 40.10 ± 11.36 mg (p = 0.754). In the PACU (Table 2), a smaller proportion of patients in the CA group required opioids (9.5%) than in the DNS group (25.0%), but this difference did not reach statistical significance (p = 0.064). The mean OME doses in the PACU were significantly higher in the DNS group than in the CA group (3.13 ± 5.99 vs. 1.31 ± 4.29 mg; p = 0.044).

Postoperative pain NRS between the DNS and CA groups

Table 4 summarizes the NRS pain scores from POD0 to POD2. The mean NRS when patients returned to the ward showed no significant difference between the DNS (2.38 ± 1.52) and CA groups (2.52 ± 1.74; p = 0.753). On POD 1, the mean NRS was significantly higher in the DNS group (1.73 ± 0.73) than in the CA group (1.41 ± 0.76; p = 0.025). By POD 2, the mean NRS in the DNS group was also significantly higher than in the CA group (1.62 ± 0.71 vs. 1.34 ± 0.79; p = 0.031).

Adverse events between the DNS and CA groups

In the safety domain, Table 4 summarizes antiemetic prescribing as an indirect assessment of postoperative nausea and vomiting (PONV). Antiemetics were administered to 19 patients (19.79%) in the DNS group and 11 patients (26.19%) in the CA group, with no statistically significant difference (p = 0.402). Table 4 also compares emergency department (ED) revisits and unplanned rehospitalizations attributable to postoperative complications. Overall, ED revisit rates were 13.54% (DNS) versus 21.43% (CA) (p = 0.244); pain-related ED revisits were 5.21% versus 9.52% (p = 0.455); and bleeding-related ED revisits were 9.38% versus 19.05% (p = 0.111). No nausea-related ED revisits were observed in either cohort. Unplanned rehospitalization occurred in 0% of the DNS group versus 4.76% of the CA group (p = 0.091).

Post hoc analysis

A post hoc analysis was conducted to evaluate the potential confounding effect of parecoxib dosages. To account for the confounding influence of parecoxib, multivariable logistic regression was performed. Parecoxib dosage was stratified into low-dose (≤ 120 mg) and high-dose (> 120 mg) groups based on the overall mean dosage of 119.71 mg. In the multivariable model (Table 5), DNS administration remained significantly associated with reduced inpatient opioid prescription (OR = 0.378, 95% CI: 0.172–0.834, p = 0.016). However, high-dose parecoxib did not show a significant independent effect on inpatient opioid prescription reduction (OR = 0.847, 95% CI: 0.391–1.835, p = 0.673).

Table 5.

Multivariable logistic regression for the analysis of inpatient opioid prescriptions

Variable	Odds ratio	95% Confidence interval	p value
Dinalbuphine sebacate	0.378	0.172–0.834	0.02
High-dose parecoxib	0.847	0.391–1.835	0.67

Discussion

To our knowledge, this is the first observational study to characterize perioperative analgesic dosing in a cohort undergoing multilevel sleep surgery performed entirely via a transoral robotic approach (TORS). Compared with conventional UPPP or UPPP plus tongue-base radiofrequency, the robotic platform is specifically engineered to facilitate the precise resection of deep-seated tissue within a narrow operative corridor, which typically results in larger and deeper tongue-base defects than earlier techniques. Consequently, the postoperative pain burden in this cohort would be expected to be at least comparable to—if not greater than—that observed after traditional procedures.

Our study demonstrated that, compared to the CA group, DNS significantly reduced short-term postoperative opioid requirements while maintaining comparable analgesic efficacy. However, patients in the DNS group exhibited a significantly higher mean NRS pain score on POD1 (1.73 ± 0.72 vs. 1.41 ± 0.76, p = 0.025) and POD2 (1.62 ± 0.71 vs. 1.34 ± 0.79; p = 0.031). Despite statistical significance, the absolute differences were only 0.32 and 0.27, which were unlikely to be clinically meaningful. This discrepancy may be attributed to the influence of extreme values. Given the minimal numerical difference, this finding may not suggest a substantial difference in actual pain perception between the groups. Similarly, we observed that the DNS group had significantly higher OME doses in the PACU. However, the absolute difference was only 1.82 mg, which is also unlikely to have clinical significance.

We observed that the cumulative doses of various analgesics, except for parecoxib, were significantly lower in the DNS group. Post hoc analyses further indicated that while higher cumulative doses of parecoxib were associated with a trend toward reducing post-operative opioid requirements, this effect did not reach statistical significance (OR: 0.847, 95% CI: 0.391–1.835, p = 0.673). Therefore, parecoxib cannot be considered a significant confounding factor in assessing the effects of DNS. Nevertheless, these findings suggest a potential synergistic interaction between DNS and parecoxib, which may contribute to the overall reduction in cumulative analgesic consumption. Previous studies have demonstrated that parecoxib effectively reduces both resting and swallowing pain visual-analog-scale (VAS) scores within 48 h of UPPP without inducing respiratory depression [24, 25]. This characteristic may further enhance the analgesic efficacy of DNS. However, the combined use of DNS and parecoxib as part of an MMA regimen requires further validation through larger, multicenter clinical trials in order to establish its clinical relevance and optimize postoperative pain management strategies.

Compared with conventional analgesia, DNS was associated with a 24.6% absolute and ≈45% relative reduction in any inpatient opioid exposure (NNT ≈ 4), a 19.4% absolute reduction in discharge opioid prescribing (NNT ≈ 5), and a 38.8% absolute reduction at the first outpatient follow-up (NNT ≈ 3) (Table 3). DNS also reduced inpatient OME by ≈41 mg on average (Table 2), a ≈73% relative decrease. Although mean NRS values on POD1–2 were modestly lower in the CA cohort (between-group differences ≤ 0.32 points), these differences fall below commonly cited minimal clinically important thresholds for acute postoperative pain, suggesting limited clinical salience. Safety outcomes (ED revisits, unplanned rehospitalizations) did not differ significantly (Table 4). In aggregate, the data support clinically meaningful opioid stewardship without compromising analgesia to a degree likely to be meaningful to patients. These findings exhibited reduced opioid requirements at discharge and during the first follow-up outpatient visit. Among discharged patients, 68.75% received opioid prescriptions, which aligns with the prescription patterns identified in a previous large retrospective study [26]. Evidence suggests that sleep surgeons tend to prescribe opioids to UPPP patients postoperatively [27]. While this trend may be partly attributed to physician preferences, reduced opioid prescriptions in the DNS group could reflect adequate analgesia achieved by this regimen, thereby decreasing postoperative opioid consumption and prescription. Reducing initial opioid prescriptions may mitigate opioid reliance, conferring additional benefits to patients [11].

The overall ED readmission rate after discharge was 16.67% (22/132), consistent with prior studies [28]. Of these, 9 patients (6.82%) were readmitted due to pain, and 17 patients (12.88%) were readmitted due to bleeding, highlighting that uncontrolled pain and bleeding remain critical concerns after UPPP surgery. While ER readmission rates did not differ significantly between the two groups, the DNS group exhibited a lower proportion of pain-related ER readmissions (5.21% vs. 9.52%). This difference, although not statistically significant, may warrant further exploration in studies with larger sample sizes in order to realize adequate statistical power. Notably, in the CA group, two patients required re-hospitalization. One was readmitted for pain management and received analgesic treatment. The other patient was readmitted due to a combination of pain and bleeding and underwent observation, hemostatic intervention, and analgesic treatment. No patients in the DNS group experienced rehospitalization.

Adverse events associated with DNS, such as dizziness, nausea, and vomiting, were frequently reported in previous studies [16]. In our study, the rates of antiemetic use during hospitalization did not differ significantly between the DNS and CA groups. Most patients received a single dose of antiemetic medication only on the day of surgery, and none required further treatment for dizziness, nausea, or vomiting after discharge.

Several analgesics, such as ketorolac [29] and celecoxib [30], have been shown to reduce postoperative opioid consumption and requirement in UPPP patients. Compared to these medications, DNS offers notable convenience. Unlike usual enhanced recovery after surgery (ERAS) protocols, which often involve a combination of multiple administrative routes—such as local anesthetic infiltration, parenteral analgesics, and oral analgesics—DNS relies solely on single intramuscular injections, simplifying drug administration. Additionally, DNS provides prolonged drug release lasting up to 145.2 h, reducing the frequency of medical interventions for pain relief. DNS has demonstrated significant postoperative analgesic effects in various surgeries, including hemorrhoidectomy [31] and laparoscopic bariatric surgery [32]. However, its application in otolaryngological surgeries remains underexplored. Our study provides preliminary evidence supporting the use of DNS in this field.

Regarding the clinical application and adaptability of this study, our results should be interpreted in the context of current guidance for OSA/OSAHS surgical patients. ASA and SASM recommendations highlight the need to limit systemic opioids, prioritize non-opioid multimodal analgesia, and implement appropriate postoperative monitoring in OSA [20]. The AAO-HNSF guideline similarly promotes judicious opioid prescribing after ENT procedures [21]. Evidence from TORS-focused ERAS pathways shows that structured multimodal protocols reduce opioid exposure and improve pain outcomes [19]. Against this backdrop, the observed association between DNS use and lower inpatient opioid exposure and reduced discharge opioid prescribing suggests that incorporating a long-acting opioid-sparing component within a comprehensive multimodal pathway may help operationalize these recommendations in TORS-UPPP programs. At the same time, institutions should tailor implementation to local resources and maintain vigilance for respiratory risk in OSA, consistent with guideline cautions [33].

This study has several limitations. First, due to its retrospective design, we could only minimize and evaluate the impact of confounding factors through patient selection and post hoc analyses. Although logistic regression analysis indicated that parecoxib did not significantly influence the reduction in opioid consumption during the first two postoperative days, unmeasured confounding factors might still exist. Future studies should explore the role of parecoxib more thoroughly and employ stricter statistical controls in order to validate more true effects of DNS. Second, the use of DNS was based on patient preference rather than random assignment, patients with better financial status or greater pain sensitivity may have been more likely to choose DNS. Moreover, variations in physicians’ recommendations for DNS could have resulted in an uneven distribution of patients across different surgeons, potentially influencing surgical factors. These issues may affect the interpretation of our findings and highlight the need for future randomized controlled trials to confirm the results. Third, the overall sample size was limited due to the retrospective design. Some findings, such as differences in pain-related ER readmission rates, may have been affected by inadequate statistical power. These results do not necessarily reflect the absence of a true effect but rather the limitations of sample size. Future research with larger cohorts is necessary to clarify these observations. Otherwise, the NRS assessments in this study were conducted at different time points and by different nurses. In future research, pain assessments should be further standardized to enhance inter-rater reliability. Finally, the study population was restricted to a single medical center. To enhance the external validity of DNS in postoperative pain management after UPPP, future multi-center randomized controlled trials are recommended to evaluate its application across diverse medical settings and compare its efficacy with other analgesic strategies.

Conclusions

A single dose of DNS (150 mg) administered at anesthesia induction significantly reduced the OME doses from POD0 to POD2 after the patient’s return to the ward, providing analgesic efficacy comparable to that of conventional protocols. Furthermore, a second dose of DNS administered 5–7 days postoperatively significantly reduced opioid prescriptions at discharge and during the first outpatient follow-up. There were no significant differences in ED readmission rates due to pain, bleeding, or nausea between the DNS and CA groups. Combining DNS with parecoxib may offer a more effective analgesic strategy for UPPP patients, warranting further investigation in randomized controlled trials.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

Conceptualization: Chien-Han Tsao, Cheng-Wei Li. Data curation: Chien-Han Tsao. Formal analysis: Cheng-Wei Li. Funding acquisition: Yueh-Hsien Hsu. Investigation: Cheng-Wei Li, Chien-Han Tsao. Methodology: Cheng-Wei Li, Chien-Han Tsao. Project administration: Chien-Han Tsao. Resources: Chien-Han Tsao. Software: Cheng-Wei Li. Supervision: Yueh-Hsien Hsu, Chien-Han Tsao. Validation: Cheng-Wei Li. Visualization: Cheng-Wei Li. Writing—original draft: Cheng-Wei Li. Writing—review & editing: Chien-Han Tsao, Yueh-Hsien Hsu.

Funding

This study was funded by a research grant of NT$80,000 from the Department of Medical Research, Chung Shan Medical University Hospital (Grant Number: CSH-2025-A-010).

Data availability

The raw data supporting the conclusions of this article will be made available by the corresponding authors upon request.

Declarations

Conflict of interest

The authors declare no competing interests.

Institutional review board statement

This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (name of institution blinded for review) (IRB number: CS1-24073).

Informed consent

The requirement for informed consent was waived because of the retrospective design of the study.