Clinical trial NCT04156581
Conditions: Opioid Use Pain, Postoperative
Sponsor: Hospital for Special Surgery, New York
Start date: 2019-11-19; Completion date: 2022-06-18
Enrollment: 46 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Enhanced recovery pathways (ERPs) emphasize evidence-based, multimodal anesthetic and analgesic choices to minimize opioid consumption while providing adequate pain control after surgery. Although ERPs for spine surgery are now being described, few pathways include regional analgesia. The Erector Spinae Plane Block (ESPB) may represent a novel opportunity to incorporate regional analgesia into ERPs for spine surgery. To date, there is minimal data to support the utility of ESPB in spine surgery, and this block has not yet been evaluated in complex spine surgery.

This study seeks to see whether ESPB will reduce opioid consumption and pain scores, and improve patient recovery during the first 24 hours after complex spine surgery when included in a comprehensive ERP.

Detailed description:
Lumbar spinal fusion with posterior approach is a moderate-severely painful procedure requiring significant postoperative opioid analgesia (Mathiesen, 2013). There are limited opportunities to use multimodal analgesia (MMA) and regional analgesia after spine surgery. For example, non-steroidal anti-inflammatory drugs are not universally provided, due to concerns regarding bleeding and impaired fusion (Sivaganasan, 2017). Likewise, local anesthetic-based techniques may cause motor weakness and sensory changes which interfere with interpretation of the early postoperative neurological examination.

As in other orthopedic subspecialty surgeries, enhanced recovery pathways (ERPs) are now being described in spine surgery (Wang 2017; Soffin 2018; Soffin 2019a; Ali 2019). Published data emphasizes the importance of opioid-sparing MMA to achieve analgesia and minimize opioid-related side effects. However, with the exception of a report from our group, none include regional analgesia or field blocks as an element of care (Soffin 2019b). Further, comparative research regarding the benefits of regional analgesia within standardized ERPs is lacking for other surgical modalities - even within subspecialties where the evidence base to support such trials is more advanced. These deficits highlight an opportunity to demonstrate the unique advantages of regional analgesia over and above that which can be provided by conventional oral and/or intravenous MMA.

Ultrasound-guided erector spinae plane block (ESPB) may represent a novel opportunity to apply regional analgesia to patients undergoing spine surgery. First described in 2016, ESPB provides analgesia by depositing local anesthetic deep to the erector spinae muscles (Forero 2016). Studies have not completely defined the mechanism of the block, but the target of the local anesthetic has been proposed to be unmyelinated C fibers / sensory cell bodies within the dorsal root ganglia (Ivanusic 2018).

Since its introduction, hundreds of case reports with a wide spectrum of indications have described ESPB as a useful analgesic adjunct for a wide range of indications (Tsui 2019). The feasibility of ESPBs in spine surgery has likewise been suggested in case reports (Almeida 2019; Chin 2019), case series (Melvin 2018; Singh 2018) and retrospective cohort studies (Ueshima 2019). Each conclude significant opioid-sparing capacity and improved NRS pain scores in patients who receive ESPB for a variety of spine surgery procedures.

More recently, results from 2 RCTs describing outcomes after ESPB for lumbar decompression have been reported. In the first, 60 patients were randomized to receive bilateral ESPB or no intervention (Yayik 2019). NRS scores and tramadol consumption were significantly lower in the first 24 hours after surgery, and the time to requesting opioid analgesia was significantly longer in patients were received ESPB. In the second RCT, postoperative morphine consumption was lower in patients who received ESPB compared to patients who did not receive ESPB (Singh, 2019). NRS scores were lower up to 6 hours after surgery in the ESPB group, and patient satisfaction scores were higher.

These preliminary RCTs are promising; however, both suffer from methodological flaws, including lack of power, inadequate blinding, and incomplete standardization of other intra- and post-operative analgesics.

Arms: arm 1: 23 complex spine surgery patients will be randomized to receive intraoperative ultrasound-guided bilateral ESPB with 0.375% bupivacaine plus 2 mg preservative free dexamethasone, 25-30 mL total per side according to patient weight. arm 2: 23 complex spine surgery patients will be randomized to receive intraoperative ultrasound-guided bilateral ESPB with saline placebo, 25-30 mL total per side according to patient weight.
Interventions: intervention 1: Bupivacaine intervention 2: Dexamethasone intervention 3: Saline
Intervention descriptions: intervention 1: Bupivacaine is administered typically to reduce sensation in an area. It acts as a nerve block for surgical procedures. intervention 2: Dexamethasone is a corticosteroid that reduces inflammation. intervention 3: Saline is a mixture of NaCl and water that can be used as a placebo.

Protocol documents:
Prot_SAP_000.pdf: 
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Erector Spinae Plane Block versus conventional analgesia in complex spine 
surgery: A randomized controlled trial 
FUNDER: Anesthesiology Research Department 
PROTOCOL NO.: 2019-1282 
VERSION & DATE: 1/2/2024 
 
 
 
 
 
 
 
 
 
 
 
 
This document contains the confidential information of the Hospital for Special Surgery.  It is provided 
to you and your company’s personnel for review.  Your acceptance of this document constitutes an 
agreement that you will not disclose the information contained herein to others without the prior written 
consent of the Hospital for Special Surgery.  No other use or reproduction is authorized by Hospital for 
Special Surgery, nor does the Hospital for Special Surgery assume any responsibility for unauthorized 
use of this protocol. 
 


 
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TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................ 2 
PROTOCOL SYNOPSIS ........................................... 4 
1.0 
INTRODUCTION ............................................. 6 
2.0 
OBJECTIVE OF CLINICAL STUDY ............... 6 
3.0 
STUDY HYPOTHESES .................................. 6 
4.0 
STUDY DESIGN ............................................. 6 
4.1 
Study Duration ................................................................................................................ 6 
4.2 
Endpoints ....................................................................................................................... 6 
4.2.1 
Primary Endpoint ...................................................................................................... 6 
4.2.2 
Secondary Endpoints ................................................................................................ 6 
4.3 
Study Sites ..................................................................................................................... 7 
5.0 
STUDY POPULATION ................................... 7 
5.1 
Number of Subjects ........................................................................................................ 7 
5.2 
Inclusion Criteria............................................................................................................. 7 
5.3 
Exclusion Criteria ........................................................................................................... 7 
5.4 
Randomization ............................................................................................................... 8 
6.0 
PROCEDURES ............................................... 8 
6.1 
Surgical Procedure ......................................................................................................... 8 
6.2 
Medical Record Requirements ....................................................................................... 8 
6.3 
Data Collection ............................................................................................................... 8 
6.4 
Schedule of Assessments .............................................................................................. 9 
7.0 
STATISTICAL ANALYSIS ............................ 10 
8.0 
ADVERSE EVENT ASSESSMENT .............. 10 
8.1 
Adverse Event (AE) ...................................................................................................... 10 
8.2 
Serious Adverse Events (SAE) .................................................................................... 10 
8.3 
Adverse Event Relationship ......................................................................................... 10 
9.0 
INVESTIGATOR RESPONSIBILITIES, RECORD 
AND REPORTS ....................................................... 11 
9.1 
Subject Consent and Information ................................................................................. 11 
9.2 
Subject Data Protection ............................................................................................... 11 
9.3 
Staff Information ........................................................................................................... 11 
9.4 
Protocol Reviews.......................................................................................................... 11 


 
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10.0 
REFERENCES ........................................... 11 
 
 
 


 
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PROTOCOL SYNOPSIS 
Protocol Title: 
Erector Spinae Plane Block versus conventional analgesia 
in complex spine surgery: A randomized controlled trial 
Protocol Number: 
2019-1282 
Protocol Date: 
1/3/2024 
Sponsor: 
Anesthesiology Department 
Principal 
Investigator: 
Ellen Soffin, MD 
Products: 
N/A 
Objective: 
The purpose of this study is to conduct a randomized 
controlled trial on patients undergoing complex spine 
surgery to whether bilateral erector spinae plane block 
(ESPB) reduces opioid consumption and pain scores and 
improves the quality of patient recovery. 
Study Design: 
Randomized Clinical Trial 
Enrollment: 
46 
Subject Criteria: 
Inclusion: 
• Age 18-80 
• Planned primary complex spine surgery: >2 level- 
lumbar and/or thoraco-lumbar spine fusion with or 
without decompression. 
• Planned stand-alone posterior surgical approach.  
• Able to follow study protocol. 
• Able to communicate in English (outcome 
questionnaires validated in English) 
Exclusion: 
• Age <18 or >80 
• Revision surgery 
• BMI > 35 
• planned prolonged intubation/intubation overnight 
on night of surgery. 
• Unable to communicate in English. 
• History of chronic pain condition requiring 
gabapentin/pregabalin/antidepressant medication 
longer than 3 months 
• Opioid tolerance (>60 OME daily for >2 weeks) 
• Allergy, intolerance, or contraindication to any 
protocol component/study medication/technique 
• Patient refusal of regional analgesia (ESPB) 


 
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Study Duration: 
• 5 years 
Data Collection: 
Sources: EPIC, Medical Records, and Patient Reported. 
 
Variables: DOB, Race, Gender, NRS pain scores at rest, 
Name, Opioid consumption, Time to opioid consumption, 
Pathway process measures, Side effects, QoR15, Blinding 
assessment 
Statistical Analysis: Proposed analysis: 
Two sample t-test  
Wilcoxon rank-sum test 
Interim analysis planned? No 
Alpha level: 0.05 
Beta or power level: 0.80 
Number of groups being compared: 2 
Resulting number per group: 21 
Total sample size: 46 (40+ 10% to account for attrition) 
 
 
 
 


 
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1.0 INTRODUCTION 
Enhanced recovery pathways (ERPs) emphasize evidence-based, multimodal 
anesthetic and analgesic choices to minimize opioid consumption while providing 
adequate pan control after surgery. Although ERPs for spine surgery are now being 
described, few pathways include regional analgesia. The ESPB may represent a 
novel opportunity to incorporate regional analgesia into ERPs for spine surgery.  To 
date, there is minimal data to support the utility of ESPB in spine surgery, and this 
block has not yet been evaluated in complex spine surgery.  The purpose of this 
study is to determine the efficacy of bilateral ESPB on postoperative pain and opioid 
consumption within a comprehensive ERP for complex spine surgery. 
2.0 OBJECTIVE OF CLINICAL STUDY 
It is currently unclear if ESPB improves outcomes after complex spine surgery.  This 
study may improve outcomes by minimizing opioids and opioid-related side effects, 
while providing adequate analgesia.  If beneficial, the ESPB may be introduced into 
routine care, representing a valuable opportunity to apply regional techniques to the 
anesthetic management of spine surgery patients.  Finally, the study offers an 
opportunity to refine the way we manage post-operative pain and opioids and to 
improve recovery after complex spine surgery. 
3.0 STUDY HYPOTHESES 
Hypothesis: An ERP for complex spine surgery which includes bilateral ESPB 
(compared to no block) will reduce opioid consumption and pain scores and improve 
patient recovery during the first 24 hours after surgery. 
4.0 STUDY DESIGN 
 
4.1 Study Duration 
5 years 
4.2 Endpoints 
4.2.1 Primary Endpoint 
• Total opioid consumption up to the first 24 hours after surgery 
(intraoperative + postoperative) in mean oral morphine equivalents 
(OME). 
4.2.2 Secondary Endpoints 
• Pain scores: numeric rating scale (NRS) pain at rest, at PACU/hour 0 
(initial), 6, 12, and 24 hours after surgery. 


 
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• Pain scores: NRS pain with movement at PACU/hour 0 (initial), 6, 12 
and 24 hours after surgery. 
• Quality of recovery: QoR 15 at baseline (holding area) and at 24 and 
72 hours after surgery. 
• Opioid related side effects (nausea/vomiting, pruritus, apnea, GI 
function, as indicated by passage of flatus ileus/GI side effects), 
assessed continuously up to 24 hours after surgery. 
• Blinding assessment: Bang blinding inventory at 24 hours after surgery 
• Time to opioid use (will include both time to pressing iv PCA and time 
to requesting first oral opioid) 
 
4.3 Study Sites 
Hospital for Special Surgery – Main Campus 
5.0 STUDY POPULATION 
5.1 Number of Subjects 
A total of 46 subjects will be enrolled. 
 
5.2 Inclusion Criteria 
Subjects of either gender will be included if they: 
• Age 18-80 
• Planned primary complex spine surgery: >2 level- lumbar and/or thoraco-
lumbar spine fusion with or without decompression. 
• Planned stand-alone posterior surgical approach.  
• Able to follow study protocol. 
• Able to communicate in English (outcome questionnaires validated in English) 
5.3 Exclusion Criteria 
Subjects will be excluded from the study if they: 
• Age <18 or >80 
• Revision surgery 
• BMI > 35 
• planned prolonged intubation/intubation overnight on night of surgery. 
• Unable to communicate in English. 
• History of chronic pain condition requiring 
gabapentin/pregabalin/antidepressant medication longer than 3 months 
• Opioid tolerance (>60 OME daily for >2 weeks) 
• Allergy, intolerance, or contraindication to any protocol component/study 
medication/technique 


 
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• Patient refusal of regional analgesia (ESPB) 
5.4 Randomization 
A computer-generated, 1:1 ratio randomization schedule with blocks of sizes 
4 and 6 will be created by a statistician not otherwise involved in the study. 
Participants will be randomized to 1 of 2 groups: 
• Group 1 Control 
• Group 2 Bilateral ultrasound guided ESPB 
6.0 PROCEDURES 
6.1 Surgical Procedure 
Planned primary complex spine surgery: >2 level-lumbar and/or thoraco-lumbar 
spine fusion with or without decompression. 
6.2  Medical Record Requirements 
EPIC 
6.3 Data Collection 
The following data will be collected: 
 
Pre-operative/Baseline 
• basic demographic data 
• patient weight & height, BMI 
• NRS Pain 
• QoR15 
 
Surgical procedure 
• date of surgery 
• type of surgery 
• surgery details 
• anesthesia details 
 
Follow-up visits (PACU, Post-op Hour 6, 12, 24, 72) 
• NRS Pain 
• Opioid consumption 
• Time to opioid consumption 
• QoR15 
• Blinding Assessment 
• Side effects 


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6.4 Schedule of Assessments 
Procedures 
Pre-Op 
PACU 
Post op 
Hour 6 
Post op 
Hour 12 
Post op 
Hour 24 
Post op 
Hour 72 
Identify eligible patients on 
schedule day before surgery 
X 
 
 
 
 
 
Obtain consent 
X 
 
 
 
 
 
NRS Pain 
X 
X 
X 
X 
X 
X 
Opioid consumption 
 
 
 
 
X 
 
Time to opioid consumption 
 
 
 
 
X 
 
QoR15 
X 
 
 
 
X 
X 
Blinding Assessment 
 
 
 
 
X 
 
Side effects 
 
 
 
 
X 
 


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7.0 STATISTICAL ANALYSIS 
Proposed analysis: 
Two sample t-test  
Wilcoxon rank-sum test 
Interim analysis planned? No 
Alpha level: 0.05 
Beta or power level: 0.08 
Number of groups being compared: 2 
Resulting number per group: 2 
Total sample size: 46 
 
 
8.0 ADVERSE EVENT ASSESSMENT 
All Adverse Events (AEs) will be reported in the final study report. Definitions for 
Adverse Event (AE) used in this study are listed below and are based on FDA and 
international guidelines: 
 
8.1 Adverse Event (AE) 
Any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product which does not necessarily have to 
have a causal relationship with this treatment. An adverse event (AE) can 
therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding, for example), symptom, or disease temporally associated 
with the use of a medicinal (investigational) product, whether considered 
related to the medicinal (investigational) product. 
 
8.2 Serious Adverse Events (SAE) 
The event is serious and should be reported to FDA when the patient 
outcome is: 
Death, Life-threatening, Hospitalization (initial or prolonged), Disability or 
Permanent Damage, Congenital Anomaly/Birth Defect, Required Intervention 
to Prevent Permanent Impairment or Damage (Devices), Other Serious 
(Important Medical Events). 
 
8.3 Adverse Event Relationship 
Relationship to study: definitely, probably, possibly, not related. 


 
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9.0 INVESTIGATOR RESPONSIBILITIES, RECORD AND REPORTS 
 
9.1 Subject Consent and Information 
Research assistants will screen the co-investigating surgeons' patients 
undergoing ambulatory total knee arthroplasty surgery. Screening will involve 
reviewing the patient's EPIC chart to ensure that they meet the inclusion criteria 
and are not excluded due to any of the exclusion criteria listed. Patients who 
meet the inclusion criteria will be identified as potential study participants. After 
the investigating anesthesiologists have confirmed the eligibility of all potential 
participants, one of the investigating anesthesiologists will approach the 
potential patients in the pre-operative holding area, explain the rationale for the 
study, and ask if the patient is interested in participating. 
9.2 Subject Data Protection 
Subject privacy and confidentiality will be maintained through the storage of 
study data in a password-protected computer database maintained by the 
Research Director and accessible only to the principal investigator, in addition 
to other IRB-approved study personnel. Each subject will be assigned a unique 
study number for identification in the study database. This unique study 
number will not be derived from or related to information about the individual. 
The key linking this unique study number to patient identifiers (i.e., name, 
medical record number, date of birth, registry number) will be maintained in a 
different password-protected database maintained by Research Director, to 
which only the primary investigator will have access. 
9.3 Staff Information 
Primary Investigator: Ellen Soffin, MD 
Research Coordinator: Pa Thor, PhD, 646-797-8535 
 
9.4 Protocol Reviews 
Study protocol reviewed and approved by: 
• Anesthesiology CRP 
• Hospital for Special Surgery Institutional Review Board 
10.0 REFERENCES 
1. Ali ZS, Flanders TM, Ozturk AK, Malhotra NR, Leszinsky L, McShane BJ 
et al. Enhanced recovery after elective spinal and peripheral nerve 


 
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surgery: pilot study from a single institution. J Neurosurg Spine 2019;25:1-
9. 
2. Almeida CR, Oliveira AR, Cunha P. Continuous bilateral erector spine 
plane block at T8 for extensive spine fusion surgery: Case report. Pain 
Pract 2019; Feb 13. doi: 10.1111/papr.12774 
3. Chin KJ, Lewis S. Opioid-free analgesia for posterior spinal fusion surgery 
using erector spinae plane (ESP) blocks in a multimodal anesthetic 
regimen. Spine (Phila Pa 1976) 2019;44(6):E379-383. 
4. Forero M, Adhikary SD, Lopez H, Tsui C, Chin KJ. The erector spinae 
plane block: A novel analgesic technique in thoracic neuropathic pain. Reg 
Anesth Pain Med 2016;41():621-7.  
5. Ivanusic J, Konishi Y, Barrington MJ. A cadaveric study investigating the 
mechanism of action of erector spinae blockade. Reg Anesth Pain Med. 
2018;43(6):567-571. 
6. Mathiesen O, Dahl B, Thomsen BA, Kitter B, Sonne N, Dahl JB et al. A 
comprehensive multimodal pain treatment reduces opioid consumption 
after multilevel spine surgery. Eur Spine J 2013;22(9):2089-2096. 
7. Melvin JP, Schrot RJ, Chu GM, Chin KJ. Low thoracic erector spinae pane 
block for perioperative analgesia in lumbosacral spine surgery: a case 
series. Can J Anaesth 2018;65(9):1057-1065. 
8. Singh S, Chaudhary NK. Bilateral ultrasound guided erector spinae plane 
block for postoperative pain management in lumbar spine surgery: A case 
series. J Neurosurg Anesthesiol. 2018; Jun 29. doi: 
10.1097/ANA.0000000000000518.  
9. Singh S, Choudhary NK, Lalin D, Verma VK. Bilateral ultrasound-guided 
erector spinae plane block for postoperative analgesia in lumbar spine 
surgery: A randomized control trial. J Neurosurg Anesthesiol. 2019; doi: 
10.1097/ANA.0000000000000603. 
10. Sivaganesan A, Chotai S, White-Dzuro G, McGirt MJ, Devin CJ. The 
effect of NSAIDs on spinal fusion: A cross-disciplinary review of 
biochemical, animal, and human studies. Eur Spine J 2017;26(11):2719-
2728. 
11. Soffin EM, Vaishnav A, Wetmore D, Gang C, Barber L, Beckman JD, et al. 
Design and Implementation of an Enhanced Recovery After Surgery 
(ERAS) Program for Minimally Invasive Lumbar Decompression Spine 


 
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Surgery: Initial Experience. Spine (Phila Pa 1976) 2018; Oct 15. doi: 
10.1097/BRS.0000000000002905.  
12. Soffin EM, Wetmore DS, Barber LA, Vaishnav AS, Beckman JD, Albert TJ 
et al. An enhanced recovery after surgery pathway: association with rapid 
discharge and minimal complications after anterior cervical spine surgery. 
Neurosurg Focus 2019a;46(4):E9.  
13. Soffin EM, Freeman C, Hughes AP, Wetmore DS, Memtsoudis SG, 
Girardi FP et al. Effects of A Multimodal Analgesic Pathway with 
Transversus Abdominis Plane Block for Lumbar Spine Fusion: A 
Prospective Feasibility Trial. Euro Spine 2019b. Under revision.  
14. Tsui BCH, Fonesca A, Munshey F, McFadyen G, Caruso TJ. The erector 
spinae plane (ESP) block: A pooled review of 242 cases. J Clin Anesth 
2019;53:29-34. 
15. Ueshima H, Inagaki M, Toyone T, Otake H. Efficacy of the erector spinae 
plane block for lumbar spinal surgery: A retrospective study. Asian Spine J 
2019;13(2):254-257. 
16. Wang MY, Chang PY, Grossman J. Development of an Enhanced 
Recovery After Surgery (ERAS) approach for lumbar spinal fusion. J 
Neurosurg Spine 2017; 26(4):411-418. 
17. Yayik AM, Cesur S, Ozturk F, Ahiskalioglu A, et al. Postoperative 
analgesic efficacy of the ultrasound-guided erector spinae plane block in 
patients undergoing lumbar spinal decompression surgery: A randomized 
controlled study. World Neurosurg 2019; 
doi.org/10.1016/j.wneu.2019.02.149  . 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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