Abstract
Objective(s)
To evaluate intercostal nerve block (administered with liposomal bupivacaine) compared with no regional analgesia after video-assisted thoracoscopic surgery lung resection.
Methods
In this randomized controlled trial, patients undergoing video-assisted thoracoscopic surgery were randomly assigned 1:1 to receive intercostal nerve block using liposomal bupivacaine or standard care without regional analgesia (control). The primary end point was resting pain at 24 hours postoperatively. Secondary outcomes included cumulative resting pain over 72 hours, opioid consumption in morphine milligram equivalents (MME), Total Quality of Recovery-15 scores, length of stay, and adverse events.
Results
A total of 199 patients were included (intervention, n = 100; control, n = 99). Median resting pain at 24 hours was lower with intercostal nerve block using liposomal bupivacaine than with control (2.0 [interquartile range, 1.0-3.0] vs 3.0 [interquartile range, 3.0-4.0]; P < .001). Cumulative opioid consumption was reduced by 18.0%, 13.1%, and 15.1% at 0 to 24, 24 to 48, and 0 to 48 hours, corresponding to absolute decreases of 4.7, 5.0, and 9.8 mg MME, respectively. Total Quality of Recovery-15 scores were higher in the intervention group at 24 and 48 hours (both P < .001). Median length of stay was similar (5.0 vs 6.0 days; P = .147), and overall postoperative adverse event rates were comparable between groups.
Conclusions
Compared with no regional analgesia, intercostal nerve block with liposomal bupivacaine reduced resting pain at 24 hours after video-assisted thoracoscopic surgery lung resection and was associated with lower opioid consumption and improved early recovery. However, this study cannot confirm its superiority over standard bupivacaine or other regional blocks.
Key Words: liposomal bupivacaine, intercostal nerve block, pulmonary resection, video-assisted thoracoscopic surgery
Graphical Abstract
Study design and end points.
Central Message.
Thoracoscopic intrathoracic intercostal nerve block may improve postoperative analgesia versus no regional analgesia after uniportal video-assisted thoracoscopic surgery.
Perspective.
In thoracoscopic lung resection patients, liposomal bupivacaine intercostal nerve block improved 48 hours postoperative recovery and reduced opioid use versus no regional analgesia. Our randomized trial found this approach did not increase adverse events or length of stay, yet our findings do not support LB's superiority over standard bupivacaine, nor ICNB's over other regional analgesic techniques.
Video-assisted thoracoscopic surgery (VATS) is widely used for lung resection.1 Despite smaller incisions and faster recovery than open surgery, postoperative pain remains common and may impair early mobilization, airway clearance, and long-term recovery.2,3 Current Enhanced Recovery After Surgery and pain guidelines recommend multimodal analgesia with reduced opioid use, and support regional analgesia after VATS.4,5
Thoracoscopy-guided intrathoracic intercostal nerve block (ICNB) is an effective regional analgesic strategy that delivers precise analgesia, but conventional local anesthetics last <24 hours. Liposomal bupivacaine (LB) offers up to 96-hour analgesia and is applicable for ICNB.2,6,7 A prior rib fracture study showed that intercostal LB infiltration, versus no regional analgesia, only transiently improved vital capacity without reducing pain or opioid use.8 However, whether ICNB with LB improves clinical outcomes after VATS compared with no regional analgesia remains to be validated by prospective studies. Accordingly, a prospective, single-site randomized controlled trial was conducted to evaluate whether thoracoscopic intrathoracic ICNB with LB during uniportal VATS (compared with no regional blockade) improves postoperative analgesia in patients undergoing uniportal VATS.
Methods
Trial Design
This randomized controlled trial was conducted at Shanghai Pulmonary Hospital to evaluate the safety and analgesic efficacy of intrathoracic LB-ICNB during uniportal VATS. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2500104552) on June 19, 2025. The protocol and statistical analysis plan are provided in the Supplementary Methods.
Sample Size Estimation and Randomization
Resting pain intensity at 24 hours after VATS served as the primary outcome measure. Based on prior data, anticipated means were 4.0 (intervention) and 4.45 (control), with an SD of 0.9. We assumed 90% power (1–β = 0.90), and equal allocation (1:1). Using the approach proposed by Chow and colleagues9 and R computations, the estimated sample size was 86 per group. Accounting for 10% attrition, we planned to enroll ≥100 per group (total ≥200). No interim analysis or discontinuation criteria were set. Participants were randomized using a computer-generated sequence with allocation concealment via sequentially numbered, sealed envelopes. Written informed consent (including for publication) was obtained before enrollment. Envelopes were then opened sequentially to assign treatment, and anesthesia/intraoperative analgesia was delivered accordingly. The study was conducted using a single-blind design, with patients and outcome assessors blinded to group allocation, whereas the operating surgeon was not blinded.
Study Population
This study was conducted at Shanghai Pulmonary Hospital, Tongji University. Registered on June 19, 2025; first patient enrolled on June 22, 2025. Eligible participants met all prespecified inclusion criteria and no exclusion criteria. After explanation of procedures and written informed consent, enrollment was completed. The protocol was approved by the hospital's Medical Ethics Committee (approval No. L25-002).
Inclusion criteria: scheduled unilateral thoracoscopic lung surgery under general anesthesia with double-lumen endotracheal intubation, age 18 to 65 years, American Society of Anesthesiologists physical status I through III, body mass index (BMI) of 18 to 28, and written informed consent. Exclusion criteria: contraindications to nerve block (eg, infection or tumor at the puncture site, unclear or abnormal local anatomy, coagulation disorders, and allergy to local anesthetics), planned postoperative intensive care unit admission, severe cardiopulmonary disease (eg, structural heart disease, severe arrhythmia, New York Heart Association functional class III or IV; acute exacerbation of chronic obstructive pulmonary disease; forced expiratory volume in the first second (FEV1) <30% predicted), severe hepatic or renal insufficiency, poorly controlled hypertension or diabetes, history of chronic pain or opioid misuse, psychiatric disorders, and inability to complete study assessments due to language barriers or severe hearing or visual impairment.
Trial Procedures
Patients were randomized to intervention or control group using a random number table. All underwent uniportal VATS (lobectomy or segmentectomy) by experienced surgeons under standardized procedures. General anesthesia used double-lumen intubation, volume-controlled 1-lung ventilation, and total intravenous anesthesia (no inhalational agents). Sufentanil was the only opioid (0.2 μg/kg IV before incision, plus 0.1 μg/kg as needed). Muscle relaxants were unrestricted. In the intervention group, thoracoscopic intrathoracic ICNB was performed at the fourth to sixth intercostal spaces (midaxillary line), injecting 0.65% LB (3 mL per level, total 9 mL). The control group received no intercostal block or other regional analgesia preoperatively or intraoperatively.
Postoperative pain management was standardized for both study groups and administered via patient-controlled intravenous analgesia, with a regimen of sufentanil at 1 μg/mL and a continuous infusion rate of 2 mL/hour. Therefore, both the control and intervention groups in this study received standard postoperative analgesic management, which was consistent with ethical requirements. Surgical management was standardized regarding incision closure and chest tube number, size, and type. Any additional analgesia (oral, intramuscular, transdermal) followed the same protocol, with dose, timing and frequency documented. Postoperative nursing was standardized forward environment, positioning, activity, and family accompaniment.
Data Collection and Outcomes
Baseline data included demographics, comorbidities, and perioperative factors. Postoperative data were collected per protocol. Opioid use was recorded and converted to intravenous morphine milligram equivalents (MME). The reported MME values reflect postoperative opioid consumption only (0 to 48 hours), including analgesia pump opioids and rescue analgesics. Resting pain was assessed using a 0 to 10 visual analog scale (VAS) at 1, 6, 12, 24, 48, and 72 hours postoperatively. Perioperative complications were prospectively monitored, including intubation- and anesthesia-related events, pneumothorax, postoperative air leak, arrhythmia, pulmonary embolism, and cerebral embolism. The resting pain score at 24 hours after surgery was the primary outcome. Subgroup analyses by age, sex, BMI, and surgical procedure were conducted and were not prespecified. Secondary outcomes included resting pain scores at prespecified time points, cumulative resting pain over 72 hours, length of hospitalization, safety events, opioid consumption (in MME), and the total Quality of Recovery-15 (TQoR-15) score. Adverse events were prospectively collected and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events. Key safety endpoints included postoperative nausea and vomiting (PONV), bradycardia, tachycardia, hypertension, and neurologic dizziness/vertigo. PONV was defined as new-onset nausea, retching, or vomiting within 48 hours postoperatively, and graded by cumulative vomiting episodes (Grade 1: 1 episode; Grade 2: 2 episodes; Grade ≥3: ≥3 episodes). Bradycardia was defined as new-onset sinus rate <60 beats/minute persisting ≥5 minutes, and tachycardia as sinus rate >100 beats/minute persisting ≥5 minutes; both were graded from 1 (asymptomatic, <1 minute) to 5 (death) per Common Terminology Criteria for Adverse Events. Hypertension was defined as new-onset blood pressure elevation requiring clinical intervention, with grading based on antihypertensive therapy intensity and evidence of end-organ damage. Neurologic dizziness/vertigo was graded by limitation of activities of daily living. Grade ≥3 events for any end point triggered immediate cessation of the study intervention and initiation of standardized rescue protocols. Comprehensive operational definitions and grading criteria are provided in Appendix E1. In addition, a post hoc analysis of the primary outcome was performed after adjusting for operative time.
Data Analysis
Analyses followed the intention-to-treat principle, with interpolation for missing data. Cumulative resting pain over 72 hours was defined as the area under the pain score–time curve calculated by the trapezoidal method. Categorical variables are presented as n (%), continuous variables as mean ± SD or median (interquartile range [IQR]), as appropriate. The choice between parametric and nonparametric tests for continuous variables was prespecified based on normality and homogeneity of variance. Normality was evaluated before analysis; Student t test was used when assumptions were met, otherwise the Wilcoxon rank-sum test. Categorical variables were compared using χ2 or Fisher exact test as appropriate. Bonferroni correction was applied for multiple testing. Analyses used SPSS version 27.0 (IBM-SPSS Inc) and R version 4.5.2 (R Foundation for Statistical Computing).
Results
Baseline Characteristics and Participant Enrollment
A total of 227 participants underwent screening, and 17 were excluded. The remaining 210 participants were randomized 1:1 to the control or intervention group (n = 105 each). Two scheduled procedures were cancelled in the control group. In addition, informed consent was withdrawn before surgery by 4 control participants and 5 intervention participants. Consequently, 199 patients were included in the final analysis (control, n = 99; intervention, n = 100) (Figure 1). The Consolidated Standards of Reporting Trials diagram is shown in Figure E1. Both the intervention and the comparator were delivered in accordance with the study protocol.
Figure 1.
Flow diagram of patient enrollment and analysis. VATS, Video-assisted thoracoscopic surgery.
Figure E1.
Consolidated Standards of Reporting Trials 2025 flow diagram. Flow diagram of the progress through the phases of a randomized trial of 2 groups (ie, enrolment, intervention allocation, follow-up, and data analysis). Source: Hopewell S, Chan AW, Collins GS, et al. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ. 2025;389:e081123. doi:10.1136/bmj-2024-081123.
The baseline variables were balanced between the 2 groups, demonstrating comparability (Table 1). The median age was 55.0 years (IQR, 48.0-61.0 years) in the control group and 55.0 years (IQR, 47.0-60.0 years) in the intervention group (P = .518). BMI was similar between the groups (23.8 ± 3.2 vs 23.9 ± 2.8; P = .714). Pulmonary function was similar between groups, including forced vital capacity (FVC), FEV1, and the FEV1 to FVC ratio (FVC: 3.0 [IQR, 2.5-3.4] vs 3.2 [IQR, 2.7-3.7] L; P = .094; FEV1: 2.5 [IQR, 2.1-2.9] vs 2.6 [IQR, 2.2-3.1] L; P = .062; FEV1:FVC: 83.1% [IQR, 78.6%-86.8%] vs 82.0% [79.0%-85.0%]; P = .615). Surgical procedure types were balanced between the groups (P = .922). Operative time was similar (60 minutes [IQR, 45-79 minutes] vs 54 minutes [IQR, 45-82 minutes; P = .466). The distribution of surgical type did not differ between groups (P = .922): segmentectomy, 51 (51.5%) versus 49 (49.0%); lobectomy, 31 (31.3%) versus 32 (32.0%); and wedge resection, 17 (17.2%) versus 19 (19.0%) (control vs intervention). In summary, no statistically significant differences were observed between the groups.
Table 1.
Baseline characteristics
| Variable | Control | Intervention | P value |
|---|---|---|---|
| Age (y) | 55.0 (48.0-61.0) | 55.0 (47.0-60.0) | .518 |
| Sex | .918 | ||
| Female | 68 (68.7) | 67 (67.0) | |
| Male | 31 (31.3) | 33 (33.0) | |
| BMI | 23.8 ± 3.2 | 23.9 ± 2.8 | .714 |
| ASA | .765 | ||
| 1 | 46 (46.5) | 45 (45.0) | |
| 2 | 52 (52.5) | 52 (52.0) | |
| 3 | 1 (1.0) | 3 (3.0) | |
| Smoking | 1 | ||
| None | 7 (77.8) | 7 (77.8) | |
| Yes | 2 (22.2) | 2 (22.2) | |
| Hypertension | 20 (100.0) | 19 (100.0) | .873 |
| Heart rate (bpm) | 80 (75-87) | 80 (75-86) | .706 |
| Mean arterial pressure (mm Hg) | 54 (51-58) | 54 (50-58) | .729 |
| Hb (g/L) | 132 (126-143) | 134 (125-141) | .717 |
| FVC (L) | 3.0 (2.5-3.4) | 3.2 (2.7-3.7) | .094 |
| FEV1 (L) | 2.5 (2.1-2.9) | 2.6 (2.2-3.1) | .062 |
| FEV1% FVC (%) | 83.1 (78.6-86.8) | 82.0 (79.0-85.0) | .615 |
| Anesthesia time (min) | 74 (60-90) | 70 (55-91) | .431 |
| Surgery time (min) | 60 (45-79) | 54 (45-82) | .466 |
| Surgical type | .922 | ||
| Segmentectomy | 51 (51.5) | 49 (49.0) | |
| Lobectomy | 31 (31.3) | 32 (32.0) | |
| Wedge resection | 17 (17.2) | 19 (19.0) | |
| Surgical site | .285 | ||
| Right side | 55 (55.6) | 64 (64.0) | |
| Left side | 44 (44.4) | 36 (36.0) |
Values are presented as median (interquartile range), mean ± SD, or n (%). BMI, Body mass index; ASA, American Society of Anesthesiologists Physical Status Classification System; Hb, hemoglobin; FVC, forced vital capacity; FEV1, forced expiratory volume in the first second.
Postoperative Pain Intensity and Analgesic Requirement
At 24 hours postoperatively, the resting pain VAS was lower in the intervention group than in the control group (2.00 [IQR, 1.00-3.00] vs 3.00 [IQR, 3.00-4.00]; P < .001; Cliff's δ [intervention − control] = −0.585; 95% CI, −0.695 to −0.470) (Figure 2, A). Compared with controls, the intervention demonstrated a significantly lower cumulative resting pain score within 72 hours after surgery (111.4 ± 59.0 vs 167.6 ± 46.3; difference, −56.2; 95% CI, −71.0 to −41.4; Bonferroni P < .001) (Figure 2, B). Resting pain scores at all the postoperative time points were significantly reduced with the intervention, except at 6 hours, with the greatest difference noted between 12 and 48 hours (Figure 2, C). The largest between-group differences were observed at 12, 24, and 48 hours, and the point estimates at these time points were consistent with the 1-point minimal clinically important difference.10
Figure 2.
Postoperative pain and opioid use. A, Resting pain at 24 hours. B, Zero to 72-hour cumulative resting pain (area under the curve). C, Resting pain over time (1 to 72 hours). Points indicate medians and error bars indicate interquartile range [IQR]. D, Opioid consumption (morphine milligram equivalents) over 0 to 24 hours, 24 to 48 hours, and 0 to 48 hours. In box-and-whisker plots, boxes indicate IQRs, center lines indicate medians, and whiskers indicate minimum and maximum nonoutlier values. P values denote between-group comparisons. VAS, Visual analog scale; MME, morphine milligram equivalents.
Cumulative opioid use, expressed as MME, was lower in the intervention group than in the control group, and these between-group differences remained statistically significant after Bonferroni adjustment (Figure 2, D). Compared with control, the intervention reduced opioid consumption by 18.0% (95% CI, 10.4%-25.3%) in 0 to 24 hours, 13.1% (95% CI, 2.8%-22.3%) in 24 to 48 hours, and 15.1% (95% CI, 6.8%-22.6%) in 0 to 48 hours. In absolute terms, opioid consumption was reduced by 4.7 MME during 0 to 24 hours, 5.0 MME during 24 to 48 hours, and 9.8 MME over 0 to 48 hours in the intervention group compared with the control group. In short, ICNB was associated with lower postoperative pain levels and reduced opioid consumption compared with no regional analgesia.
Postoperative Recovery and Hospitalization Outcomes
As shown in Figure 3, A, TQoR scores increased over time within each group. TQoR scores were significantly higher with the intervention at 24 and 48 hours (P < .001). To further investigate differences in postoperative recovery quality between the intervention and control groups, we categorized the scales into the following types: medical service satisfaction, overall well-being and overall evaluation, psychological emotions and subjective perceptions, daily living and social functioning, and physiological functioning and physical symptoms. At 24 and 48 hours, the intervention group showed higher domain scores than the control group, and the trajectories rose more steadily over time (Figure 3, B). These findings indicate that ICNB was associated with better early postoperative recovery within the first 48 hours versus no regional analgesia.
Figure 3.
Quality of recovery and length of stay. A, Total Quality of Recovery-15 questionnaire (TQoR) scores at 24, 48, and 72 hours. B, Mean QoR domain scores over time in each group.
The length of stay was 5.0 days (IQR, 5.0-6.0 days) in the control group and 6.0 days (IQR, 5.0-7.0 days) in the intervention group. However, this difference was not statistically significant (P = .147). The rates of postoperative adverse events were comparable across groups, including PONV, hypertension, dizziness, bradycardia, and tachycardia (Table 2). PONV incidence decreased over time in both groups (Figure E2), with no significant between-group differences at 6, 24, or 48 hours, or within 48 hours overall (P > .05).
Table 2.
Posttreatment safety outcomes data
| Outcome | Control | Intervention | P value |
|---|---|---|---|
| Hypertension | 3 (3.0) | 3 (3.0) | 1.000 |
| Tachycardia | 1 (1.0) | 0 (0.0) | .497 |
| Bradycardia | 1 (1.0) | 1 (1.0) | 1.000 |
| Neurological dizziness | 1 (1.0) | 1 (1.0) | 1.000 |
| PONV_6 h | 40 (40.4) | 34 (34.0) | .350 |
| PONV_24 h | 28 (28.3) | 24 (24.0) | .492 |
| PONV_48 h | 7 (7.1) | 5 (5.0) | .540 |
| Any_PONV_within_48 h | 53 (53.5) | 49 (49.0) | .522 |
Values are presented as n (%). PONV, Postoperative nausea and vomiting.
Figure E2.
Postoperative nausea and vomiting (PONV) incidence over time. PONV incidence at 6, 24, and 48 hours after surgery in the control and intervention groups.
Post Hoc Analysis
After adjusting for surgery time, the resting pain VAS at 24 hours was significantly lower in the intervention group than in the control group (95% CI, −1.49 to −0.95; P < .001).
Exploratory Analyses
The treatment effect appeared generally consistent across subgroups (age, sex, BMI, and surgical procedure), with no statistically significant evidence of heterogeneity (Figure E3). However, these subgroup analyses were exploratory and should be interpreted with caution.
Figure E3.
Subgroup analysis of rest 24-hour visual analog scale. Forest plot of treatment effects. IQR, Interquartile range; BMI, body mass index.
Discussion
The principal finding of this trial is that, compared with no regional analgesia, the addition of thoracoscopic ICNB administered with LB to standard postoperative systemic analgesia was associated with lower postoperative pain, lower opioid consumption, and improved early recovery after uniportal VATS (Figure 4).
Figure 4.
The study evaluate intercostal nerve block (administered with liposomal bupivacaine) compared with no regional analgesia after video-assisted thoracoscopic surgery lung resection.
However, because the control group received no regional blockade, the observed reductions in pain and opioid use may reflect the effect of ICNB itself rather than LB specifically. Although several randomized trials have recently reported that liposomal bupivacaine may reduce opioid use or improve postoperative recovery, it remains controversial whether it is superior to standard bupivacaine or placebo.6, 7, 8,11, 12, 13, 14, 15, 16, 17, 18, 19, 20 Although improved pain control may theoretically reduce the risk of PONV and facilitate earlier discharge, no significant between-group differences were observed for these end points in our study, only a trend toward reduction, which may be related to limited statistical power and low event rates.18,21 No between-group differences were observed in length of stay or other process measures.12,18,22 This likely reflects our standardized discharge pathway, under which length of stay is influenced more by routine care and administrative timing than by differences in analgesia.
Clinically, poor thoracic pain control limits breathing and coughing, so effective analgesia is essential for perioperative respiratory care. Both groups had rising TQoR scores; intervention was better at 24 hours (difference = 10.31 greater than minimal clinically important difference [clinically meaningful]) and 48 hours (difference = 7.64 near minimal clinically important difference [possible clinical relevance]).23 Intervention reduced opioid consumption, consistent with opioid-sparing goals and potentially lowering adverse event risks. However, given expected differences between regional block and systemic analgesia, the study cannot determine the liposomal formulation's specific contribution; observed benefits likely stem from the regional block itself.1,24,25
Several limitations exist. Most importantly, the trial did not include an active regional comparator, such as standard bupivacaine ICNB or an alternative block. Thus, this study cannot demonstrate that the intervention is superior to other blocks or that LB is better than standard bupivacaine. Additionally, the nondouble blind design without sham injection carried performance bias. The single-center, restrictive eligibility limited generalizability to older or obese patients, and findings only applied to uniportal VATS. Finally, the trial was powered solely for the primary end point, with some unprespecified analyses and only resting pain assessed.
Conclusions
In summary, thoracoscopic intrathoracic ICNB improved early analgesia and reduced opioid use without worse safety or longer length of stay versus no regional blockade. Larger studies are warranted, and current findings do not confirm LB's superiority over standard bupivacaine or ICNB over other regional blocks.
Conflict of Interest Statement
The authors reported no conflicts of interest.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
Footnotes
This study is funded by the Shanghai Pulmonary Hospital Research Physician Talent Program Project (LYRC202412).
Drs Lu, Wei, and Tang contributed equally to this article.
Clinical Trial Registry Number: ChiCTR2500104552 (www.chictr.org.cn).
Ethics approval (IRB/ERB-equivalent): This study was approved by the Medical Ethics Committee of Shanghai Pulmonary Hospital on June 19, 2025 (L25-002).
Informed Consent Statement: All patients provided written informed consent prior to screening, including consent to participate in the trial and to publish the study data.
Data Availability Statement: Data are available from the corresponding author upon reasonable request due to privacy/ethical restrictions.
Appendix E1. Terms, Definitions, and Grading and Safety Intervention Rules
Postoperative Nausea and Vomiting (PONV)
Definition
PONV is defined as new-onset nausea, retching, or vomiting occurring within 0 to 48 h after the patient leaves the operating room. Causes unrelated to the study intervention must be excluded, including preoperative baseline symptoms, postoperative ileus/bowel obstruction, intracranial lesions, and drug allergy.Nausea is an unpleasant sensation in the epigastrium with an urge to vomit.Vomiting is the forceful expulsion of gastric or proximal small-bowel contents through the esophagus and mouth due to strong gastric contractions.
Grading and safety intervention rule
-
•
Grade 0: no vomiting.
-
•
Grade 1: 1 episode of vomiting within 48 hours postoperatively (cumulative).
-
•
Grade 2: 2 episodes of vomiting (cumulative).
-
•
Grade 3: ≥3 episodes of vomiting (cumulative).
Grade 3 is defined as the safety-event threshold in this study. If Grade 3 occurs, the study intervention must be stopped immediately and a standardized antiemetic rescue protocol must be initiated.
Bradycardia
Definition
Bradycardia is defined as sinus rhythm with a heart rate <60 beats/minute. Within 0 to 48 h after the patient leaves the operating room, exclude preexisting baseline sinus bradycardia, atrioventricular block, or other underlying arrhythmias. Study bradycardia refers to new-onset arrhythmia originating from the sinoatrial node, with a resting heart rate <60 beats/min persisting for ≥5 minutes.
Grading and safety intervention rule
-
•
Grade 1 (mild): asymptomatic; duration <1 minute; no intervention required.
-
•
Grade 2 (moderate): duration ≥1 minute, and/or associated symptoms (eg, palpitations and chest tightness); no emergency intervention required.
-
•
Grade 3 (severe): symptomatic with hemodynamic instability; requires urgent intervention.
-
•
Grade 4 (life-threatening): cardiac arrest or life-threatening malignant arrhythmia.
-
•
Grade 5: death.
Safety threshold trigger
If Grade 3 sinus bradycardia occurs, stop the study intervention immediately. Initiate electrocardiogram (ECG) monitoring and continuous vital-sign monitoring. Evaluate precipitating factors. Start the institution’s standardized antiarrhythmic/resuscitation protocol.
Tachycardia
Definition
Within 0 to 48 hours after the patient leaves the operating room, exclude preexisting baseline sinus tachycardia and tachycardia due to nonstudy-intervention factors such as anemia, hypovolemia, infection, pain, or other causes. Study tachycardia refers to new-onset arrhythmia originating from the sinoatrial node, with a resting heart rate >100 beats/minute persisting for ≥5 minutes.
Grading and safety intervention rule
-
•
Grade 1 (mild): asymptomatic; duration <1 minute; no intervention required.
-
•
Grade 2 (moderate): duration ≥1 minute, and/or associated symptoms (eg, palpitations and chest tightness); no emergency intervention required.
-
•
Grade 3 (severe): symptomatic with hemodynamic instability; requires urgent intervention.
-
•
Grade 4 (life-threatening): cardiac arrest or life-threatening malignant arrhythmia.
-
•
Grade 5: death.
Safety threshold trigger
If Grade 3 sinus tachycardia occurs, stop the study intervention immediately. Initiate ECG monitoring and continuous vital-sign monitoring. Evaluate precipitating factors. Start the institution’s standardized antiarrhythmic/resuscitation protocol.
Hypertension
Definition
Within 0 to 48 hours after the patient leaves the operating room, exclude elevated blood pressure due to preexisting hypertension or nonstudy-intervention factors such as pain, anxiety, fluid overload, or urinary retention. Hypertension is defined as new-onset blood pressure elevation confirmed at rest by 2 repeat measurements 5 minutes apart, reaching a level that requires clinical intervention.
Grading and safety intervention rule
-
•
Grade 1 (mild): compared with baseline, systolic blood pressure (SBP) increase ≥20 mm Hg or diastolic BP (DBP) increase ≥10 mm Hg; or in previously normotensive patients, repeat-confirmed SBP 140 to 159 mm Hg or DBP 90 to 99 mm Hg; requires no medication or single-agent therapy only.
-
•
Grade 2 (moderate): requires combination therapy with two antihypertensive agents; or addition of one agent/increased intensity compared with the preoperative regimen.
-
•
Grade 3 (severe): requires ≥3 antihypertensive agents; or hypertensive emergency (SBP ≥180 mm Hg or DBP ≥120 mm Hg) with evidence of end-organ damage.
-
•
Grade 4 (life-threatening): malignant hypertension, hypertensive encephalopathy, acute heart/kidney/liver failure, or other life-threatening complications.
-
•
Grade 5: death.
Safety threshold trigger
If Grade 3 hypertension or higher occurs, stop the study intervention immediately. Initiate continuous BP monitoring. Evaluate precipitating factors. Start the institution’s standardized hypertensive-emergency management protocol.
Neurologic Dizziness/Vertigo
Definition
New-onset dizziness/vertigo within 0 to 48 hours after leaving the operating room due to structural or functional abnormalities of the vestibular pathway. Exclude nonneurogenic causes, including hemodynamic instability, metabolic disturbances, medication effects, and pain-related lightheadedness. Core symptoms include a sensation of spinning or swaying, neurogenic gait unsteadiness, and impaired spatial orientation.
Grading and safety intervention rule
-
•
Grade 1: no limitation of activities of daily living (ADL).
-
•
Grade 2: limitation of instrumental ADL.
-
•
Grade 3: limitation of basic self-care ADL.
-
•
Grade 4: life-threatening.
-
•
Grade 5: death.
Grade ≥3 is defined as the safety threshold in this study. If triggered, stop the study intervention immediately and initiate standardized rescue management.
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