Erector Spinae Plane Block as Pain Management After Lumbar Fusion Surgery (RCT-ESPB)

Erector Spinae Plane Block for Reduction of Early Postoperative Pain Scores and Opioid Use in Lumbar Spinal Fusion Surgery, a Prospective Double-blinded Randomized Placebo-controlled Trial

Rationale: Lumbar spine surgery is associated with high postoperative pain scores and analgesic use, despite use of multimodal analgesia. The erector spinae plane block (ESPB) is a promising locoregional anesthetic technique for this type of surgery. The literature is not yet conclusive about the effectiveness of this technique on reducing postoperative pain intensity.

Objective: The objective of this study is to evaluate the analgesic effect of ESPB as add-on therapy to multimodal analgesia on early postoperative pain intensity after lumbar spinal fusion surgery compared to placebo.

Study design: The study is designed as a prospective mono-centre, randomized, double-blinded, placebo-controlled trial.

Study population: 76 patients ≥ 18 years of age requiring elective lumbar spinal fusion surgery involving one to four fusion levels.

Intervention: Patients will receive ultrasound-guided ESPB with either ropivacaine or placebo at the end of surgery.

Main study parameters/endpoints: Main study parameter is pain intensity upon emergence from anesthesia measured with the Numeric Rating Scale. A minimal clinically important difference is considered to be a decrease of 1.5 points. Secondary endpoints are pain intensity during hospital stay and after 30 days, opioid use during hospital stay and after 30 days, opioid side effects, use of anti-emetics, time to first opioid use/request, length of hospital stay, quality of recovery at discharge.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The Sint Maartenskliniek is experienced in applying locoregional analgesia, the use of ropivacaine and using sonography. The procedure of administering ESPB has a very low risk of complications. Receiving placebo is justifiable because this group will not be withhold standard treatment. The risks of receiving placebo are negligible. The patients will visit the clinic at regular follow-up moments.

Study Overview

• Status: Completed
• Conditions: Lumbar Disc Herniation; Lumbar Spinal Stenosis; Fusion of Spine; Spinal Fusion; Lumbar Spondylolisthesis; Spondylolisthesis; Lumbar Disc Disease; Lumbar Spondylosis; Lumbar Spine Disease; Lumbar Radiculitis; Spondylosis Lumbosacral Region
• Intervention / Treatment: Drug: Ropivacaine Hydrochloride Injection; Drug: Sodium chloride

Detailed Description

Rationale: Lumbar spine surgery is associated with high postoperative pain scores and analgesic use. Despite multimodal pain treatment, time to first rescue treatment with opioids is often short and necessary on the Post Anesthesia Care Unit (PACU). Latest scientific insights show most pain interventions produce mild analgesic effects, and advise a multimodal regimen based upon systemic analgesics consisting of at least gabapentoids, ketamine and opioids. Therefore, in our clinic (Sint Maartenskliniek, Nijmegen, the Netherlands), multimodal analgesia in spine surgery is now gold standard, with opioids as first choice postoperative rescue treatment. However, despite multimodal treatment, patients who underwent lumbar spine surgery still develop severe postoperative pain.

A different possible measure to lower the risk of postoperative pain is locoregional anesthesia. The Sint Maartenskliniek has a long history of applying locoregional anesthesia in orthopedic surgery. Locoregional anesthesia provides effective analgesia without systemic side-effects like drowsiness or nausea, thereby reducing perioperative systemic drug use and possibly reducing the risk of persistent postsurgical pain. A novel locoregional anesthetic technique is the erector spinae plane block (ESPB). Good quality evidence exists for the effectiveness of this technique in breast cancer surgery and video assisted thoracoscopy (VATS). Although ESPB seems a promising analgesic technique for lumbar spine surgery patients not responding to the multimodal pain treatment regimen, sufficient high quality evidence is lacking. A recent systematic review summarized the evidence of ESPB for lumbar spine surgery, including two randomized clinical trials (RCT), showing beginning evidence of reduced postoperative opioid consumption and decreased pain scores. However, these trials contained a small sample size, were not blinded or lacked a comparator. Furthermore, little information on postoperative hospital stay is provided. This results in ESPB not being widely accepted in lumbar spine surgery. The larger, double-blinded, placebo-controlled methodology in this proposed trial aims to contribute to the scientific evidence for the effectiveness of EPSB in a multimodal analgesia management setting.

Objective: The primary objective of the study is to evaluate the analgesic effect of ESPB on early postoperative pain after lumbar spinal fusion surgery. Therefore the pain intensity in the postoperative care unit upon emergence, using the Numeric Rating Scale (NRS) for pain, will be the primary outcome parameter of this study. The null hypothesis states there is no difference in effectiveness of the ESPB compared to placebo on early postoperative pain intensity measured with NRS in patients that underwent lumbar spinal fusion surgery. This hypothesis will be tested two-sided, with α = 0.05.

Study design: This study is designed as a prospective, mono-center, double-blinded, randomized, placebo controlled trial. The study will be performed at the Sint Maartenskliniek, Nijmegen, the Netherlands. The study will be performed in accordance with the ICH E6(R1) Good Clinical Practice (GCP) guidelines. The duration of the study will be determined according to the progress of inclusion. Patients scheduled for elective lumbar spinal fusion surgery will be studied. Subject of investigation is the locoregional anesthetic technique ESPB. Subjects will be randomized to receive either ESPB with a long-acting local anesthetic or normal saline (placebo).

The staff involved (doctors, nurses, OR-personal), as well as the research team and the patient will be blinded for treatment allocation. The study period includes in-hospital time after surgery and follow-up 30 days after surgery. Placement of the ESPB will be performed according to the study protocol, at the end of surgery, after wound closure. The placement of the ESPB is performed according to daily clinical practice as described by Forero et al. Postoperative treatment of patients will be according to standard hospital protocol for lumbar spinal fusion surgery.

Study population: 76 patients undergoing elective lumbar spinal fusion surgery involving one to four fusion levels will be recruited.

Main study parameters/endpoints: Main study parameter is pain intensity upon emergence from anesthesia measured with the Numeric Rating Scale. A minimal clinically important difference is considered to be a decrease of 1.5 points. Secondary endpoints are pain intensity during hospital stay and after 30 days, opioid use during hospital stay and after 30 days, opioid side effects, use of anti-emetics, time to first opioid use/request, length of hospital stay, quality of recovery at discharge.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The Sint Maartenskliniek is experienced in applying locoregional analgesia, the use of ropivacaine and using sonography. The procedure of administering ESPB has a very low risk of complications. Receiving placebo is justifiable because this group will not be withhold standard treatment. The risks of receiving placebo are negligible. The patients will visit the clinic at regular follow-up moments.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: I.H. van de Wijgert, MSc, MD; Phone Number: +31243272593; Email: i.vandewijgert@maartenskliniek.nl

Study Locations

• Netherlands
  • Gelderland
    • Ubbergen, Gelderland, Netherlands, 6500GM
      • Sint Maartenskliniek

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years;
• Patients planned for elective lumbar spinal fusion surgery with a dorsal surgical approach;
• 1-4 fusion level spine surgery;
• Written informed consent.

Exclusion Criteria:

• A Body Mass Index (BMI) > 40 kg/m²;
• ASA physical health classification > 3;
• Patients who will undergo spine surgery involving less than 2 or more than 4 levels of fusion, scoliosis surgery*;
• Patients who will undergo circumferent spine surgery;
• Patients with an active, local infection or systemic infection;
• Patients with an allergy to one or more medications used in the study;
• Patients with any contraindication to a regional anesthetic technique;
• Kidney- or liver failure inhibiting the systemic use of paracetamol and/or NSAIDs;
• Acute surgeries;
• Patients with a history of drugs or alcohol abuse;
• Pregnancy;
• Cognitive impairment;
• Inability to speak or understand the Dutch language.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ESPB with ropivacaine; Patients in the experimental group will receive locoregional analgesia via ESPB with injectate consisting of ropivacaine 0.375 mg/mL with no additives, two times 30mL bilaterally at the transverse processs of the T12-vertebra (total dose of 225 mg).	Drug: Ropivacaine Hydrochloride Injection; Investigating the effectiveness of erector spinae plane block with ropivacaine for lumbar spinal fusion surgery versus placebo.; Other Names: SMPC h104944; Ropivacaine HCl
Placebo Comparator: ESPB with placebo; Patients in the placebo group will receive an injection performed as the procedure of ESPB with injectate consisting of sodiumchloride 0.9% with no additives, two times 30mL bilaterally at the transverse processs of the T12-vertebra.	Drug: Sodium chloride; Placebo comparator; Other Names: NaCl 0.9%; SMPC h55227

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity one hour after arrival at post-anesthesia care unit	Numeric Rating Scale (NRS) for pain 0-10 (0 = no pain, 10 = maximum pain) as asked by PACU-nurse	1 hour after arrival at PACU

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acceptability of pain	Yes/no	1 hour after arrival at PACU
Opioid use	total morphine equivalent dose as extracted from the electronic medical file and PCIA pump	0-12 hours, 12-24 hours after surgery
Presence of opioid side effects	Nausea, vomiting and use of anti-emetics as documented in electronic medical file	12 hours, 24 hours after surgery
Time to first opioid use/request	defined as minutes	12 hours after surgery
Time to first mobilization	defined as hours	72 hours after surgery
Length of hospital stay	defined as days	up to 30 days after surgery
Pain intensity	Numeric Rating Scale (NRS) for pain 0-10 (0 = no pain, 10 = maximum pain)	on postoperative admission days, 30 days
Opioid use	Do you use opioids yes/no	30 days after surgery
Quality of recovery	Quality of Recovery-15 questionnaire (Dutch version). Score 0-150 (0 = worst recovery, 150 = perfect recovery)	Postoperative day 1 and 3
Adverse events	(Serious) adverse events during study period	0-30 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drain wound leakage	mLs of drain wound leakage, if drain is present	Postoperative day 1, 2 and 3

Collaborators and Investigators

• Sponsor: Ilse van de Wijgert
• Collaborators: Radboud University Medical Center
• Investigators: Principal Investigator: M.G.E. Fenten, MSc, PhD, MD, Sint Maartenskliniek

Publications and helpful links

General Publications

• 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 Sep-Oct;41(5):621-7. doi: 10.1097/AAP.0000000000000451.
• 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. 2020 Oct;32(4):330-334. doi: 10.1097/ANA.0000000000000603.
• Yayik AM, Cesur S, Ozturk F, Ahiskalioglu A, Ay AN, Celik EC, Karaavci NC. 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 Jun;126:e779-e785. doi: 10.1016/j.wneu.2019.02.149. Epub 2019 Mar 8.
• Gerbershagen HJ, Aduckathil S, van Wijck AJ, Peelen LM, Kalkman CJ, Meissner W. Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures. Anesthesiology. 2013 Apr;118(4):934-44. doi: 10.1097/ALN.0b013e31828866b3.
• Alboog A, Bae S, Chui J. Anesthetic management of complex spine surgery in adult patients: a review based on outcome evidence. Curr Opin Anaesthesiol. 2019 Oct;32(5):600-608. doi: 10.1097/ACO.0000000000000765.
• Huang W, Wang W, Xie W, Chen Z, Liu Y. Erector spinae plane block for postoperative analgesia in breast and thoracic surgery: A systematic review and meta-analysis. J Clin Anesth. 2020 Nov;66:109900. doi: 10.1016/j.jclinane.2020.109900. Epub 2020 Jun 2.
• Qiu Y, Zhang TJ, Hua Z. Erector Spinae Plane Block for Lumbar Spinal Surgery: A Systematic Review. J Pain Res. 2020 Jul 1;13:1611-1619. doi: 10.2147/JPR.S256205. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Actual): December 19, 2023
• Study Completion (Actual): January 19, 2024

Study Registration Dates

• First Submitted: March 28, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (Actual): April 25, 2022

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Postoperative pain; Regional anesthesia; Erector spinae block; Lumbar interbody fusion
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Pathological Conditions, Anatomical; Bone Diseases; Hernia; Spondylolysis; Intervertebral Disc Displacement; Radiculopathy; Spinal Diseases; Spinal Stenosis; Spondylosis; Spondylolisthesis; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Ropivacaine
• Other Study ID Numbers: 0984; 2021-003679-32 (EudraCT Number); NL9640 (Other Identifier: Netherlands Trial Register)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: DANS EASY will be data repository for open access.
• IPD Sharing Time Frame: After end of inclusion period for at least 5 years.
• IPD Sharing Access Criteria: DANS EASY will be data repository for open access. FAIR Guiding Principles are followed to make data Findable, Accessible, Interoperable and Reusable. An Open Access-licence is required to consult the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No