A Study of Ropivacaine Complex Methylene Blue Fascia Iliaca Compartment Block on Analgesia in Patients Undergoing Hip Arthroplasty
Phase: NA
Conditions: Femoral Neck Disease
Sponsor: Wang wanxia

Study Protocol and Statistical Analysis Plan
Official title：Analgesic Effect of Ropivacaine Combined
with Methylene Blue in Fascia Iliaca Block for Patients
Undergoing Hip Arthroplasty
NCT number：NCT06284941
Date：December 24, 2024

For inclusion in this study, patients of either sex had to meet the requirements for hip
replacement surgery, be in the age range of 65–85 years, have a body mass index
(BMI) in the range of 18–28 kg/m2, be categorized as American Society of
Anesthesiologists (ASA) grade II to III, have no history of analgesic or local
anesthetic allergies, and have no history of alcoholism or narcotic drug abuse. Patients
were excluded if they met any of the following criteria: refusal by patient or family
member to participate in the study, having a serious mental illness or inability to
communicate clearly
with researchers,
severe
coagulopathy, allergy
to local
anesthetics, severe psychiatric illness or other communication disorder, history of
neurological disease such as Guillain-Barré syndrome, infection at the puncture site,
delay in awakening post-surgery for more than 60 min, post-surgical use of an
analgesic pump, and inability to follow-up at the required time points.
Randomization and Blinding
Using a computer-generated random sequence, a person who was not involved in the
experimental operation divided the patients into two groups in which FICB was
achieved with either methylene blue and ropivacaine (MB+R group) or ropivacaine
only (R group). All serial numbers were encoded sequentially, kept, and scheduled for
each experiment by someone other than the researcher. Because methylene blue is a
blue liquid, exposure to the color could expose the experimental group. Thus, blinding
was achieved by having different researchers perform different steps in the study to
avoid the color affecting the experiment. The steps of the experimental procedure,

including the extraction of the liquid medicine, performance of the nerve block, and
postoperative follow-up, were performed by different anesthesiologists, who were
only responsible for independent experimental procedures, did not know the
information about the patient outside the experiment, and did not communicate with
each other about the patient and the experiment. Catheterization was not performed
for any patient to prevent the color of the urine from exposing the experimental group.
Operative Procedures
Nerve Block
Before general anesthesia induction, FICB was performed under ultrasound guidance
using the Edge II ultrasound device (Sonosite, USA). With the patient in supine
position and the surgical area disinfected, the high-frequency ultrasound probe was
placed perpendicular on the inguinal ligament. The probe was slowly moved until the
“bowtie sign” created by the internal oblique and sartorius muscles was observed.
This sign corresponds to the confluence of the fascia lata and fascia iliaca, which
represents the fascia iliaca compartment. With an in-plane technique in the caudal to
cranial direction, the needle tip was inserted deep to the fascia iliac. After confirming
it could be withdrawn without blood, local anesthetic drugs in a volume of 30 ml were
injected. Patients in the MB+R group received 0.25% ropivacaine (Product Batch
Number: EE2344, Zhejiang Xianju Pharmaceutical Co., Ltd.) and 0.05% methylene
blue (Product Batch Number: 2310032, Jichuan Pharmaceutical Group Co., Ltd.), and
those in the R group received only 0.25% ropivacaine (same batch number).

Induction and Maintenance of Anesthesia
After successful nerve block, all patients were transferred to the operating room
where they received routine monitoring of heart rate (HR), electrocardiogram (ECG),
oxygen saturation (SpO2), etc. Radial artery puncture catheterization was performed
under local anesthesia for invasive arterial pressure monitoring. For anesthesia
induction, patients received an intravenous injection of propofol 1.0–2.0 mg/kg,
rocuronium bromide 0.6 mg/kg, and sufentanil 0.2–0.3 µg/kg. The specifications of
mechanical ventilation after endotracheal intubation were: tidal volume (VT) 6–8
ml/kg, respiratory rate (RR) 10–12 times/min, positive end expiratory pressure (PEEP)
3–5 cmH₂O, and end-expiratory carbon dioxide partial pressure (PETCO2) 35~45
mmHg. Anesthesia was maintained by inhalation of 1.5%–2.0% sevoflurane along
with intravenous infusion of remifentanil at 0.05–0.2 µg/kg/min and intermittent
administration of rocuronium bromide 5–10 mg according to the intraoperative
situation to maintain muscle relaxation. Blood pressure (BP) and HR fluctuation
within 20% of baseline values was allowed according to the intraoperative situation.
If BP dropped by >20% of the baseline value or if systolic BP was <90 mmHg,
ephedrine 6 mg was given. If the HR was <50 beats/minute, an intravenous bolus of
atropine 0.5 mg was given. All operations among included patients were performed by
the same surgical team with the same surgical method, and the surgical method was
hip replacement with posterolateral approach in the lateral decubitus position. The
inhalation of sevoflurane and infusion of remifentanil was stopped 5 min before the
end of the operation. After surgery, the patient was transferred to a recovery room, and

the endotracheal tube was removed once the patient was awake and spontaneous
breathing had resumed. According to our pre-test experience, many patients refuse the
use of analgesic pumps due to the relatively high cost, certain drug-related side effects,
and the option of FICB. Thus, we did not include cases with post-surgical use of an
analgesic pump in this study. In this study, fascia iliaca block was used to administer
postoperative analgesia to patients. If the patients were not satisfied with the effect of
fascia iliaca block, additional opioids were used for supplemental analgesia. At the
same time, to avoid the effect of drugs on the level of patients’ inflammatory factors,
the use of non-steroidal analgesic drugs was prohibited.
Study Outcomes
Primary Outcomes
As a measure of pain, Visual Analog Scale (VAS) scores at both rest and with activity
(passive straight leg raise at 45°) were recorded at the following time points: before
block and at 2, 6, 12, 24, and 48 h postoperatively. The VAS score is a common way
to assess pain using a sliding ruler about 10 cm long, marked with 10 scales on one
side and "0" and "10" at each end. A score of 0 indicates no pain; a score of 10
indicates the most severe pain that is unbearable. The higher the score, the greater the
degree of pain. In this study, a dedicated anesthesiologist assessed the pain of each
included participant at different time points before and after surgery.
Secondary Outcomes
As indicators of inflammation, the values of hypersensitive C-reactive protein

(hs-CRP), procalcitonin (PCT), and the neutrophil-to-lymphocyte ratio (NLR) also
were recorded on postoperative days 1 and 2.
HR and mean arterial pressure (MAP) values were recorded at the following time
points: operating room entry (T1), immediately before skin incision (T2), 1 min after
skin incision (T3), skin suture (T4), and 30 min after extubation (T5). The
requirement of supplemental analgesia was noted within 48 h postoperatively, along
with the number of times patients got out of bed to perform activities within 48 h
postoperatively and the distance walked after the patient’s first attempt to get out of
bed. Any occurrence of adverse reactions such as nausea, vomiting, and arrhythmia
within 48 h postoperatively also was recorded. Any drug-related nerve damage after
surgery was noted. Nerve deficits were defined according to sensory findings: 0—no
nerve damage, 1—minor sensory paresthesia, 2—complete sensory parasthesia,
3—complete motor defect with or without sensory paresthesia, and 4—complex
regional pain syndrome. Two researchers who were blinded to the group allocation
assessed these outcomes.
Statistical Methods
SPSS 25.0 software was used for statistical analysis. Normally distributed data were
expressed as mean ± SD, and group comparisons were performed using independent
samples t-test. Data with a skewed distribution were expressed as median (M) and
interquartile range (IQR), and non-parametric tests were used for comparisons.
Friedman’s test was used for intra-group comparisons. Count data were expressed as

number (%), and comparisons between groups were performed using the χ² test.
P<0.05 was considered statistically significant.