Intravenous Ketorolac Substantially Reduces Opioid Use and Length of Stay After Lumbar Fusion: A Randomized Controlled Trial

Overview

Journal Spine (Phila Pa 1976)

Specialty Orthopedics

Date 2023 Sep 22

PMID 37737686

Authors

Sravisht Iyer

Michael E Steinhaus

Gregory S Kazarian

Evangelia M Zgonis

Matthew E Cunningham

James C Farmer

Han Jo Kim

Darren R Lebl

Russel C Huang

Virginie Lafage

Frank J Schwab

Sheeraz Qureshi

Federico P Girardi

Bernard A Rawlins

James D Beckman

John A Carrino

J Levi Chazen

Jeffrey J Varghese

Hamna Muzammil

Renaud Lafage

Harvinder S Sandhu

Affiliations

Soon will be listed here.

Abstract

Study Design: A randomized, double-blinded, placebo-controlled trial.

Objective: To examine the effect of intravenous ketorolac (IV-K) on hospital opioid use compared with IV-placebo (IV-P) and IV acetaminophen (IV-A).

Summary Of Background Data: Controlling postoperative pain while minimizing opioid use after lumbar spinal fusion is an important area of study.

Patients And Methods: Patients aged 18 to 75 years undergoing 1 to 2 level lumbar fusions between April 2016 and December 2019 were included. Patients with chronic opioid use, smokers, and those on systemic glucocorticoids or contraindications to study medications were excluded. A block randomization scheme was used, and study personnel, hospital staff, and subjects were blinded to the assignment. Patients were randomized postoperatively. The IV-K group received 15 mg (age > 65) or 30 mg (age < 65) every six hours (q6h) for 48 hours, IV-A received 1000 mg q6h, and IV-P received normal saline q6h for 48 hours. Demographic and surgical details, opioid use in morphine milliequivalents, opioid-related adverse events, and length of stay (LOS) were recorded. The primary outcome was in-hospital opioid use up to 72 hours.

Results: A total of 171 patients were included (58 IV-K, 55 IV-A, and 58 IV-P) in the intent-to-treat (ITT) analysis, with a mean age of 57.1 years. The IV-K group had lower opioid use at 72 hours (173 ± 157 mg) versus IV-A (255 ± 179 mg) and IV-P (299 ± 179 mg; P = 0.000). In terms of opiate use, IV-K was superior to IV-A ( P = 0.025) and IV-P ( P = 0.000) on ITT analysis, although on per-protocol analysis, the difference with IV-A did not reach significance ( P = 0.063). When compared with IV-P, IV-K patients reported significantly lower worst ( P = 0.004), best ( P = 0.001), average ( P = 0.001), and current pain ( P = 0.002) on postoperative day 1, and significantly shorter LOS ( P = 0.009) on ITT analysis. There were no differences in opioid-related adverse events, drain output, clinical outcomes, transfusion rates, or fusion rates.

Conclusions: By reducing opioid use, improving pain control on postoperative day 1, and decreasing LOS without increases in complications or pseudarthrosis, IV-K may be an important component of "enhanced recovery after surgery" protocols.

References

Evans C, Butcher C . The influence on human osteoblasts in vitro of non-steroidal anti-inflammatory drugs which act on different cyclooxygenase enzymes. J Bone Joint Surg Br. 2004; 86(3):444-9. DOI: 10.1302/0301-620x.86b3.14592. View

Bellantonio D, Bolondi G, Cultrera F, Lofrese G, Mongardi L, Gobbi L . Erector spinae plane block for perioperative pain management in neurosurgical lower-thoracic and lumbar spinal fusion: a single-centre prospective randomised controlled trial. BMC Anesthesiol. 2023; 23(1):187. PMC: 10227393. DOI: 10.1186/s12871-023-02130-z. View

Lumawig J, Yamazaki A, Watanabe K . Dose-dependent inhibition of diclofenac sodium on posterior lumbar interbody fusion rates. Spine J. 2008; 9(5):343-9. DOI: 10.1016/j.spinee.2008.06.455. View

Fogarty D, OHanlon J, Milligan K . Intramuscular ketorolac following total hip replacement with spinal anaesthesia and intrathecal morphine. Acta Anaesthesiol Scand. 1995; 39(2):191-4. DOI: 10.1111/j.1399-6576.1995.tb04041.x. View

YaDeau J, Liu S, Rade M, Marcello D, Liguori G . Performance characteristics and validation of the Opioid-Related Symptom Distress Scale for evaluation of analgesic side effects after orthopedic surgery. Anesth Analg. 2011; 113(2):369-77. DOI: 10.1213/ANE.0b013e31821ae3f7. View

Chidambaran V, Subramanyam R, Ding L, Sadhasivam S, Geisler K, Stubbeman B . Cost-effectiveness of intravenous acetaminophen and ketorolac in adolescents undergoing idiopathic scoliosis surgery. Paediatr Anaesth. 2018; 28(3):237-248. PMC: 6004284. DOI: 10.1111/pan.13329. View

Dodwell E, Latorre J, Parisini E, Zwettler E, Chandra D, Mulpuri K . NSAID exposure and risk of nonunion: a meta-analysis of case-control and cohort studies. Calcif Tissue Int. 2010; 87(3):193-202. DOI: 10.1007/s00223-010-9379-7. View

Stoving K, Rothe C, Rosenstock C, Aasvang E, Lundstrom L, Lange K . Cutaneous Sensory Block Area, Muscle-Relaxing Effect, and Block Duration of the Transversus Abdominis Plane Block: A Randomized, Blinded, and Placebo-Controlled Study in Healthy Volunteers. Reg Anesth Pain Med. 2015; 40(4):355-62. DOI: 10.1097/AAP.0000000000000252. View

Horn P, Wrona S, Beebe A, Klamar J . A retrospective quality improvement study of ketorolac use following spinal fusion in pediatric patients. Orthop Nurs. 2010; 29(5):342-3. DOI: 10.1097/NOR.0b013e3181edd876. View

10.

Park S, Moon S, Park M, Oh K, Lee H . The effects of ketorolac injected via patient controlled analgesia postoperatively on spinal fusion. Yonsei Med J. 2005; 46(2):245-51. PMC: 2823021. DOI: 10.3349/ymj.2005.46.2.245. View

11.

Deguchi M, Rapoff A, Zdeblick T . Posterolateral fusion for isthmic spondylolisthesis in adults: analysis of fusion rate and clinical results. J Spinal Disord. 1999; 11(6):459-64. View

12.

Khalili G, Janghorbani M, Saryazdi H, Emaminejad A . Effect of preemptive and preventive acetaminophen on postoperative pain score: a randomized, double-blind trial of patients undergoing lower extremity surgery. J Clin Anesth. 2013; 25(3):188-92. DOI: 10.1016/j.jclinane.2012.09.004. View

13.

Sinatra R, Jahr J, Reynolds L, Groudine S, Royal M, Breitmeyer J . Intravenous acetaminophen for pain after major orthopedic surgery: an expanded analysis. Pain Pract. 2011; 12(5):357-65. DOI: 10.1111/j.1533-2500.2011.00514.x. View

14.

Karvonen S, Salomaki T, Olkkola K . Efficacy of oral paracetamol and ketoprofen for pain management after major orthopedic surgery. Methods Find Exp Clin Pharmacol. 2009; 30(9):703-6. DOI: 10.1358/mf.2008.30.9.1316919. View

15.

Ramirez-Gonzalez M, Torres-Lugo N, Deliz-Jimenez D, Echegaray-Casalduc G, Ramirez N, Colon-Rodriguez E . Efficacy of an Opioid-Sparing Perioperative Multimodal Analgesia Protocol on Posterior Lumbar Fusion in a Hispanic Population: A Randomized Controlled Trial. J Am Acad Orthop Surg. 2023; 31(17):931-937. DOI: 10.5435/JAAOS-D-22-00878. View

16.

Long J, Lewis S, Kuklo T, Zhu Y, Riew K . The effect of cyclooxygenase-2 inhibitors on spinal fusion. J Bone Joint Surg Am. 2002; 84(10):1763-8. DOI: 10.2106/00004623-200210000-00004. View

17.

Vitale M, Choe J, Hwang M, Bauer R, Hyman J, Lee F . Use of ketorolac tromethamine in children undergoing scoliosis surgery. an analysis of complications. Spine J. 2003; 3(1):55-62. DOI: 10.1016/s1529-9430(02)00446-1. View

18.

Reuben S, Connelly N, Lurie S, Klatt M, Gibson C . Dose-response of ketorolac as an adjunct to patient-controlled analgesia morphine in patients after spinal fusion surgery. Anesth Analg. 1998; 87(1):98-102. DOI: 10.1097/00000539-199807000-00021. View

19.

Pugely A, Martin C, Gao Y, Mendoza-Lattes S . Causes and risk factors for 30-day unplanned readmissions after lumbar spine surgery. Spine (Phila Pa 1976). 2014; 39(9):761-8. DOI: 10.1097/BRS.0000000000000270. View

20.

Glassman S, Rose S, Dimar J, Puno R, Campbell M, Johnson J . The effect of postoperative nonsteroidal anti-inflammatory drug administration on spinal fusion. Spine (Phila Pa 1976). 1998; 23(7):834-8. DOI: 10.1097/00007632-199804010-00020. View