Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center , Taipei, Taiwan
Conditions: Surgery, Shoulder Impingement
Sponsor: Tri-Service General Hospital

Study Protocol and Statistical Analysis Plan 
 
 
Official title ： 
Tri-Service General Hospital 
NCT number： 
NCT05590767 
Document date： September 20, 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Materials and methods 
This prospective observational study was conducted in Tri-Service General Hospital, 
Taipei. Written informed consent was obtained from each participating patient the day 
before data collection and surgery. We included adult patients with American Society 
of Anesthesiology physical status I-II, who were scheduled for shoulder rotator cuff 
repair under combined ipsilateral interscalene block (ISB) and general anesthesia. 
Patients with conditions that could interfere with pupillary measurement, such as 
chronic opioid use (>3 months), the presence of ophthalmologic or neurological 
diseases, and long-term medication influencing the autonomic nervous system (e.g., 
β-blockers, anticholinergics) were excluded. 
 
Conduct of anesthesia 
On the day of the surgery, the patient was initially sent to the anesthesia preparation 
room where their vital signs, including pulse oximetry, electrocardiography, and 
noninvasive blood pressure, were monitored. A single injection ISB was performed 
using sterile technique on the ipsilateral side of the surgical site. We utilized nerve 
simulation concurrently with ultrasound guidance to ensure accurate needle tip 
placement. Following a negative aspiration, a bolus of a 15 mL mixture containing 7.5 
mL of 2% lidocaine and 7.5 mL of 0.5% ropivacaine was slowly administered in 5 mL 
increments. Then after the patient was transported to the operating room, the success 
of ISB was assessed by conducting a cold and pinprick sensory test over the C5 and 
C6 dermatomal segments. 
In addition to the standard basic monitoring, we also use Bispectral Index to monitor 
the depth of anesthesia. After preoxygenation, the patient was given Fentanyl (1-1.5 
ug/kg), Lidocaine (0.5-1 mg/kg), Propofol (1.5-2 mg/kg), and Cisatracurium (0.15-0.2 
mg/kg) as induction agents to complete endotracheal intubation. Inhaled sevoflurane 
was used to maintain general anesthesia, with a targeted Bispectral Index (BIS) range 
of 40 to 60. Fentanyl is the sole analgesic permitted for use throughout the surgery. 
Subsequent administration of fentanyl and/or cisatracurium, as well as ventilator 
settings and hemodynamic management, were left to the discretion of the attending 
anesthesiologist in charge of the patient. At the end of the surgery, sevoflurane was 
discontinued and neuromuscular block was reversed with neostigmine and 
glycopyrrolate. The patient was extubated once they were able to open their eyes on 
verbal command and resume spontaneous breathing, with a train-of-four ratio greater 
than 0.9 using a neuromuscular stimulator. 
Within 15 minutes of the patient being transported to the post-anesthesia care unit 
(PACU), nursing staff would ask the patient to rate their pain at the surgical site using 
the NRS, which ranges from 0 to 10. The choice of postoperative analgesics, if 

necessary, was decided by the responsible anesthesiologist. The rest of patient care in 
the PACU was conducted in accordance with established standards. 
 
Pupillary measurement 
We used a portable video pupillometer (AlgiScan; IDMED, Marseille, France) with its 
built-in pupillary pain index (PPI) mode to measure pupillary reflex dilation. The PPI 
mode applies a standardized, incremental transcutaneous electrical stimulation 
(100Hz, 10mA to 60mA, with 1-second intervals) that progressively increases in 
intensity until a pupil dilation of more than 13% is observed. The degree of reflex 
dilation is quantified on a scale of 1 (very deep analgesia) to 9 (very light analgesia) 
and referred to as the Pupillary Pain Index (PPI) (18-20).  
PPI measurements were conducted at two distinct time intervals: after the induction of 
general anesthesia but before the surgical incision, and before the patient was 
extubated after the end of surgery. To perform the measurement, two sets of electrodes 
were placed on the patient’s deltoid regions, one set on each side. We tested both sides 
of the C5 and C6 dermatomal segment, with one side anesthetized by ISB and the 
other side used as a control. Hence, each patient served as their own control. To 
decrease measurement bias, the PPI was recorded in the eye opposite the block by the 
same investigator, who did not influence the decision of the anesthesiologist staff. The 
PACU nurse who documented the patient’s NRS was not informed of the PPI value 
obtained. 
 
Statistical analysis 
Continuous data were reported as either means with standard deviations or medians 
with interquartile ranges (IQR), while categorical data as numbers with percentages. 
The normality of the distribution of data was assessed using the Kolmogorov-Smirnov 
and Shapiro-Wilk tests. To compare the PPI between the ISB and control sides during 
two PPI measurement time intervals, we used the paired Student’s t-test or the 
Wilcoxon signed-rank test as appropriate. To examine the correlation between 
postoperative NRS and PPI on the ISB side, we performed Pearson's (or Spearman's) 
correlation analysis accordingly. Statistical analyses were conducted using online 
statistics calculator (DATAtab: Online Statistics Calculator. DATAtab e.U. Graz, 
Austria. URL https://datatab.net). A two-tailed P value less than 0.05 was considered 
statistically significant.