Single Shot Lumbar Erector Spinae Plane (ESP) Block in Total Hip Replacement (THR): a Randomized Control Trial
Phase: NA
Conditions: Total Hip Replacement, Analgesia
Sponsor: Tuen Mun Hospital

Cover Page
Document type: Study protocol and Statistical Analysis Plan
Study title: Single Shot Lumbar Erector Spinae Plane (ESP) Block in Total Hip Replacement (THR)
NCT number: NCT04388553
Document date: 10 Dec 2020

Glossary of Terms (in alphabetical order)
ANZCA - Australian and New Zealand College of Anesthetists
ASA - American Society of Anesthesiologists
BMI - body mass index
CI - confidence interval
CONSORT - Consolidated Standards of Reporting Trials
ESP - erector spinae plane
ESPB - erector spinae plane block
GA - general anesthesia
MRC - Medical Research Council
NRS - numeric rating scale
OR - odds ratio
PCA - patient controlled analgesia
POD1 - first postoperative day
Prn - pro re nata
SD - standard deviation
THR - total hip replacement
 
 
 
 
 

INTRODUCTION
 Total hip replacement (THR) improves quality of life in pathologies like osteoarthritis, 
rheumatoid arthritis and avascular necrosis1. Postoperative complications, for instance, 
venous thromboembolism and chest infection may be prevented by early mobilization 
which is facilitated by effective pain management2,3.
 Multimodal analgesia is applied to these patients, with a combination of opioid and non-
opioid oral analgesics and regional block. Each of the components has its own limitations; 
for opioid, postoperative nausea and vomiting and respiratory depression restrict its use; 
non-steroidal anti-inflammatory drugs are contraindicated in those with renal impairment; 
and adjuvants like gabapentinoid can lead to dizziness and sedation in some patients. 
Regional techniques like femoral nerve block, lumbar plexus block and epidural 
anesthesia have shortcomings like incomplete coverage of nerves innervating the hip joint, 
limb weakness, invasiveness of the procedure and/or potential hemodynamic instability. 
Newer plane blocks like Pericapsular Nerve Group block4 and Supra-inguinal Fascia Iliaca 
block5 are emerging as candidates for analgesia after THR.  Erector spinae plane block 
(ESPB) has been described in hip surgery by Tulgar in a case report6. However, the 
evidence of lumbar ESPB was limited mainly to case reports at the time of this study being 
designed. We postulated that compared to no block, a single shot lumbar ESPB at L1 
would reduce postoperative fentanyl use and postoperative pain scores (primary 
outcomes) in a multicenter, double-blinded, randomized clinical trial in patients undergoing 
unilateral THR.
 
METHODS
 This was a multicenter, double-blinded, randomized (with a randomization ratio of 1:1), 
controlled, parallel-group study conducted in Hong Kong. The study was carried out from 
July 2020 to November 2021 in two tertiary centers, which were situated in New Territories 
West and had an annual caseload of around 450 total joint replacements. Patients were 
counselled on the potential risks of general anesthesia (GA) and ESPB during the pre-
anesthetic assessment, after which written informed consent would be obtained if they 
agreed to be recruited. This study was approved by the New Territories West Cluster 
Research Ethics Committee (reference number: NTWC/REC/20007), and was registered 
prior to patient enrollment at ClinicalTrials.gov (NCT04388553, Principal investigator: 
Anyon Chan, Link to registration page: https://clinicaltrials.gov/ct2/show/NCT04388553, 
Date of registration: May 14, 2020). The full trial protocol can also be accessed via 
ClinicalTrials.gov. This manuscript was constructed in the format suggested by the 
Consolidated Standards of Reporting Trials (CONSORT) guideline7.
Eligibility criteria
 To be eligible for the study, patient must be above 18 years old, under American Society 
of Anesthesiologists (ASA) class 1-3 and underwent primary elective unilateral THR. They 
should understand and accept the risks for GA and ESPB. They should also be able to use 
postoperative patient-controlled analgesia (PCA) and express their pain intensity in 
Numeric Rating Scale (NRS).
 Patients with the following conditions were excluded from this study: 1) emergency case, 
2) bilateral THR, 3) revision THR, 4) THR done under neuraxial technique, 5) 
contraindication for ESPB (i.e. patient refusal, mentally incapacitated, injection site 
infection, local spine pathology or surgery, coagulopathy with International Normalized 
Ratio > 1.4 or thrombocytopenia < 75 x 109/L), 6) regular strong opioid (e.g. fentanyl, 
morphine, oxycodone, methadone, heroin etc.), 7) severe obstructive sleep apnea 
syndrome (Apnea-Hypopnea Index ≥ 30), 8) severe obesity (Body Mass Index (BMI) ≥ 35).
Randomization

 Simple randomization method was employed. Allocation concealment was achieved by 
drawing randomly from a set of sealed opaque envelopes with allocation inside on the day 
before surgery, followed by attaching it to the pre-anesthetic assessment form by the 
investigator. The envelope was opened by the attending anesthetist after the patient was 
put under GA to ensure patient blinding. If the operation was cancelled or the patient could 
not use PCA postoperatively, for instance, postoperative mechanical ventilation or delirium, 
the envelope would be put back into the pool. A CONSORT diagram illustrates the 
participant flow (Figure 1).
Intervention
 After the patient was put under GA (maintained with nitrous oxide and either sevoflurane 
or desflurane), the envelope was opened. For the treatment arm, lumbar ESPB was 
performed by 4 designated anesthetists. For the control arm, no injection was performed 
and a plaster was applied to the target skin puncture site to blind the assessor. A curved 
probe (Fujifilm Sonosite Edge (Washington, United States); 2-5 MHz) was placed sagittally 
on the flank to look for the 12th rib, which was traced medially to the transverse process of 
the T12. The probe was then moved one spinal level caudad to locate the L1 vertebra with 
the L1 transverse process in the middle of the probe. A 10 cm Pajunk Sonoplex® needle 
(Geisingen, Germany) was inserted in an in-plane manner to aim at the tip of the L1 
transverse process. After hitting the bone, 0.5-1ml normal saline was used for 
hydrolocating the plane between the erector spinae muscle and the transverse process 
beneath it. Forty mL of 0.25% levobupivacaine (or a maximum of 2mg/kg body weight 
made up to the same volume) was injected into the ESP. After the block, the injection site 
was also covered with a plaster like the control arm. If the block was technically 
challenging and the anatomy was difficult to identify, the procedure would be aborted and 
the patient would be excluded from the study with the assignment envelope returned. After 
the injection, the surgeon was instructed not to infiltrate any local anesthetics into the 
wound. Intraoperatively, both arms received intravenous fentanyl (4 µg/kg in the first hour, 
2 µg/kg in the second hour and then 1 µg/kg/hour onward) as the only analgesic and 4mg 
intravenous ondansetron was given. Patients from both arms were prescribed intravenous 
PCA fentanyl as the first-line analgesia with the following setting for at least 24 hours 
postoperatively: 1) bolus dose of 40% of the corrected body weight in µg fentanyl (ideal 
body weight in kg = body height in cm -105 (female) or -100 (male), corrected body weight 
= (total body weight - ideal body weight) x 0.4 + ideal body weight); 2) no background 
infusion; 3) lock-out time of 6 minutes; and 4) 1 hour limit of 120 - 200 µg (to be decided by 
the attending anesthetist). Preoperative regular oral analgesics (paracetamol 0.5 - 4 g 
daily, non-steroidal anti-inflammatory drugs like ibuprofen 200 - 400 mg daily or diclofenac 
25 - 100 mg daily, tramadol 50 - 200 mg daily and gabapentinoids like gabapentin 100 - 
900 mg daily or pregabalin 25 - 150 mg daily) were continued postoperatively unless 
contraindicated. Oral tramadol 50mg was prescribed as the rescue analgesic and 
intravenous metoclopramide 10mg was prescribed as the rescue antiemetic. Patients were 
instructed to request prn tramadol from ward nurse if pain control was inadequate despite 
intravenous fentanyl PCA.
Outcome assessment
 Patients were followed up on POD1 by independent assessors from the acute pain 
service team consisting of a nurse and an anesthetist, who were not involved in the 
intraoperative care of the patient and was blinded by being instructed not to look at the 
anesthetic record. The primary outcomes, namely the amounts of PCA fentanyl used 12-
hour and 24-hour postoperatively (in µg) and the pain intensity at rest and on movement 
on POD1, were assessed. NRS with a scale from 0 to 10 was adopted for pain 
assessment. NRS 0 means no pain while NRS 10 means the worst pain experienced8. The 
secondary outcomes were the rates of postoperative nausea (defined as feeling of having 
an urge to vomit)9 and postoperative vomiting (defined as forcing the contents of the 

stomach up through the oesophagus and out of the mouth)9 from the end of operation till 
the follow-up on POD1 as recalled by the patient, the need of rescue antiemetic and 
analgesia in the first 24 hours postoperatively, along with knee flexion power of the 
operated limb in Medical Research Council (MRC) scale. The oral morphine equivalents of 
fentanyl and prn tramadol used at 12 hours and 24 hours postoperatively were calculated 
according to the opioid conversion table from the Faculty of Pain Medicine of Australian 
and New Zealand College of Anaesthetists (ANZCA)10. Of note, the use of antiemetic was 
not a surrogate of postoperative nausea or vomiting.
Statistical analysis
 The data were collected by the investigator and analyzed by SPSS® 26 package. Per-
protocol analysis was planned because it reflects treatment efficacy better, and any patient 
who deviated from the protocol (for instance, technically challenging block, postoperative 
mechanical ventilation and delirium) would not be analyzed. Since data of the primary 
outcomes, the oral morphine equivalents and the knee flexion power were not normally 
distributed as evidenced by skewed appearance of the histograms and p values of 
Shapiro-Wilk test smaller than 0.05, we used Mann-Whitney U test to compare these 
outcomes between treatment group and control group, while the Hodges-Lehmann 
estimator was employed to compute the median difference and the 95% confidence 
interval (CI). The proportions of postoperative nausea, postoperative vomiting and need of 
rescue antiemetic between two arms were compared by Chi-square test, whereas the 
proportions of those requiring rescue analgesia between both groups were analyzed by 2-
sided Fisher’s exact test (due to presence of expected count less than 5). Multivariable 
regression would be employed to adjust the outcomes should there be any major 
discrepancy (absolute standardized difference > 0.46 with n=35 in both groups as 
suggested by Austin11) in the perioperative factors between treatment and control groups.
Sample size estimation
 A pilot study was done by retrospectively examining cases of primary unilateral THR in the 
two tertiary centers from January to December 2019 with postoperative PCA (infusion-
plus-bolus and bolus only). The mean fentanyl use upon follow-up on the first day 
postoperatively (POD1) without regional block (including femoral nerve block/fascia iliaca 
block/lumbar plexus block/lateral cutaneous femoral nerve block/gluteal nerve block) or 
local anesthetics infiltration (n=36) was 664 µg, whereas that with regional block or local 
anesthetics infiltration (n=20) was 368 µg. To detect a reduction of fentanyl use by 300 µg 
which was comparable to data from the pilot study (Standard Deviation (SD) 438 µg), 
along with a reduction in pain score (in NRS) by 2 points (SD 2.42 for rest pain and 2.48 
for movement pain) on POD1, a sample size of 35 patients was required for both treatment 
and control arm (κ = 1) with type 1 error (α) of 0.05 and power (1-β) of 80% in two-sample 
t-test assuming equal variance and normality of data distribution12. Secondary outcomes 
were not taken in account of sample size calculation, and were considered to be 
exploratory only. No interim analysis was planned.
 
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