IV Acetaminophen for Post-Operative Pain Management in Enhanced Recovery After Surgery (ERAS) Population

NCT ID: NCT03198871

Last Updated: 2021-01-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-24
• Study Completion Date: 2020-11-30

Brief Summary

Number of patients with unsatisfactory pain relief defined as average visual analog scale (VAS) more than 5 with or without requirement of IVPCA for pain relief during the first 48 hours postoperative period will be compared between the two groups and form the primary outcome for the study. Postoperative pain intensity will be measured by Visual Analog Scale (VAS) with 0- being no pain and 10-being maximum pain and the analgesic efficacy in both groups will also be evaluated by the amount of total narcotic consumption (measured with IV morphine equivalent doses of analgesics used to provide pain relief).

Detailed Description

In response to an increased focus on improving patient outcomes and satisfaction with surgical care, a growing body of clinical evidence has recently been dedicated to enhanced recovery after surgery (ERAS) protocols. These evidence-based perioperative pathways aim to optimize patients undergoing surgery in the preoperative, intraoperative, and postoperative periods. ERAS protocols have incorporated the use of multimodal analgesia to minimize the use of intra- and postoperative opioid analgesics. Lidocaine, ketamine, magnesium, gabapentin, acetaminophen and non-steroidal anti-inflammatory drugs are some of the adjuvant analgesics used in combination with regional blocks to optimize analgesia and recovery. Multimodal analgesia has dependably been shown to significantly reduce postoperative opioid requirements as well as opioid-related side effects such as postoperative nausea and vomiting. Both oral and intravenous acetaminophen preparations have been shown to be useful adjuvants in multimodal analgesia. Intravenous acetaminophen has been of interest for its utility in post-surgical patients, who have not yet been cleared for oral intake. Intravenous acetaminophen should also be preferred over oral acetaminophen in patients after major abdominal surgery where absorption of medications given through oral route is erratic. Although the efficacy of intravenous acetaminophen as a postoperative pain adjunct is known, its exact role in ERAS protocols and non-narcotic multimodal analgesic regimens for major abdominal surgery has not been studied in randomized clinical trials to define its efficacy. The primary goal of this study is to assess the utility of a postoperative intravenous acetaminophen dosing schedule in minimizing postoperative pain, opioid consumption and opioid-related side effects. We also aim to study overall patient satisfaction and cost-effectiveness (direct and indirect costs) of this regimen as part of ERAS protocol at a large tertiary medical center.

Conditions

Abdominal Wall Hernia; Pancreatic Diseases; Bowel Disease; Gastric Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Acetaminophen Injectable Product

Acetaminophen group: Half of subjects enrolled will be randomized to the acetaminophen group

Group Type: EXPERIMENTAL

Acetaminophen Injectable Product

Intervention Type: DRUG

The interventional group will receive 1 gram intravenous acetaminophen at the start of wound closure to be repeated every 6 hours for 48 hours postoperatively

Sodium Chloride 0.9%, Intravenous

Sodium Chloride 0.9% group: Half of subjects enrolled will be randomized to the acetaminophen group

Group Type: PLACEBO_COMPARATOR

Sodium Chloride 0.9%, Intravenous

Intervention Type: DRUG

The placebo group will be given an intravenous placebo of saline solution at wound closure and repeated every 6 hours for 48 hours postoperatively.

Interventions

Acetaminophen Injectable Product

The interventional group will receive 1 gram intravenous acetaminophen at the start of wound closure to be repeated every 6 hours for 48 hours postoperatively

Intervention Type: DRUG

Sodium Chloride 0.9%, Intravenous

The placebo group will be given an intravenous placebo of saline solution at wound closure and repeated every 6 hours for 48 hours postoperatively.

Intervention Type: DRUG

Other Intervention Names

Tylenol; Paracetamol; Ofirmev; Saline

Eligibility Criteria

Inclusion Criteria

• Male or Female
• 18 years of age or older
• patients scheduled for elective colorectal, pancreatic, and other major abdominal procedure.
• Patient consent will be obtained preoperatively for eligible study participants.

Exclusion Criteria

• Patients who refuse to participate in the study or part of any other enhanced recovery after surgery (ERAS) research protocol.
• Patients with a documented allergy to acetaminophen.
• Chronic alcoholism
• Hypovolemia
• Chronic malnutrition
• Preoperative renal insufficiency (creatinine clearance less than or equal to 30ml/min) or hemodialysis
• Patients with a history of hepatic impairment, history of hepatic impairment or active hepatic disease
• severe chronic pain condition that required daily preoperative opioid dependence
• Patients with pre-existing dementia and/or other neuropsychiatric conditions impeding accurate assessment of pain scores or other study measures will be excluded.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mallinckrodt

INDUSTRY

Sponsor Role: collaborator

Kathirvel Subramaniam

OTHER

Sponsor Role: lead

Responsible Party

Kathirvel Subramaniam

Principal Investigator, Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Kathirvel Subramaniam, M.D., M.P.H

Role: PRINCIPAL_INVESTIGATOR

Associate Professor and staff Anesthesiologist

Locations

Upmc Presbyterian Montefiore Hospital

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Ziemann-Gimmel P, Hensel P, Koppman J, Marema R. Multimodal analgesia reduces narcotic requirements and antiemetic rescue medication in laparoscopic Roux-en-Y gastric bypass surgery. Surg Obes Relat Dis. 2013 Nov-Dec;9(6):975-80. doi: 10.1016/j.soard.2013.02.003. Epub 2013 Feb 13.

Reference Type: BACKGROUND

PMID: 23499469 (View on PubMed)

Ziemann-Gimmel P, Goldfarb AA, Koppman J, Marema RT. Opioid-free total intravenous anaesthesia reduces postoperative nausea and vomiting in bariatric surgery beyond triple prophylaxis. Br J Anaesth. 2014 May;112(5):906-11. doi: 10.1093/bja/aet551. Epub 2014 Feb 18.

Reference Type: BACKGROUND

PMID: 24554545 (View on PubMed)

Practice guidelines for acute pain management in the perioperative setting. A report by the American Society of Anesthesiologists Task Force on Pain Management, Acute Pain Section. Anesthesiology. 1995 Apr;82(4):1071-81. No abstract available.

Reference Type: BACKGROUND

PMID: 7717542 (View on PubMed)

Hansen RN, Pham A, Strassels SA, Balaban S, Wan GJ. Erratum to: Comparative Analysis of Length of Stay and Inpatient Costs for Orthopedic Surgery Patients Treated with IV Acetaminophen and IV Opioids vs. IV Opioids Alone for Post-Operative Pain. Adv Ther. 2016 Sep;33(9):1646-1648. doi: 10.1007/s12325-016-0400-z. No abstract available.

Reference Type: BACKGROUND

PMID: 27562836 (View on PubMed)

Bollinger AJ, Butler PD, Nies MS, Sietsema DL, Jones CB, Endres TJ. Is Scheduled Intravenous Acetaminophen Effective in the Pain Management Protocol of Geriatric Hip Fractures? Geriatr Orthop Surg Rehabil. 2015 Sep;6(3):202-8. doi: 10.1177/2151458515588560.

Reference Type: BACKGROUND

PMID: 26328237 (View on PubMed)

Herring BO, Ader S, Maldonado A, Hawkins C, Kearson M, Camejo M. Impact of intravenous acetaminophen on reducing opioid use after hysterectomy. Pharmacotherapy. 2014 Dec;34 Suppl 1:27S-33S. doi: 10.1002/phar.1513.

Reference Type: BACKGROUND

PMID: 25521844 (View on PubMed)

Jokela R, Ahonen J, Seitsonen E, Marjakangas P, Korttila K. The influence of ondansetron on the analgesic effect of acetaminophen after laparoscopic hysterectomy. Clin Pharmacol Ther. 2010 Jun;87(6):672-8. doi: 10.1038/clpt.2009.281. Epub 2010 Mar 10.

Reference Type: BACKGROUND

PMID: 20220746 (View on PubMed)

Gonzalez A, Ziemann-Gimmel P. The role of multimodal analgesia in bariatric surgery: A review of clinical data and case-based presentations featuring OFIRMEV® (acetaminophen) injection. Surgical Pain Management. 2014;11(5): A2-11.

Reference Type: BACKGROUND

Pettersson PH, Jakobsson J, Owall A. Intravenous acetaminophen reduced the use of opioids compared with oral administration after coronary artery bypass grafting. J Cardiothorac Vasc Anesth. 2005 Jun;19(3):306-9. doi: 10.1053/j.jvca.2005.03.006.

Reference Type: BACKGROUND

PMID: 16130055 (View on PubMed)

Mamoun NF, Lin P, Zimmerman NM, Mascha EJ, Mick SL, Insler SR, Sessler DI, Duncan AE. Intravenous acetaminophen analgesia after cardiac surgery: A randomized, blinded, controlled superiority trial. J Thorac Cardiovasc Surg. 2016 Sep;152(3):881-889.e1. doi: 10.1016/j.jtcvs.2016.04.078. Epub 2016 May 5.

Reference Type: BACKGROUND

PMID: 27236864 (View on PubMed)

Douzjian DJ, Kulik A. Old Drug, New Route: A Systematic Review of Intravenous Acetaminophen After Adult Cardiac Surgery. J Cardiothorac Vasc Anesth. 2017 Apr;31(2):694-701. doi: 10.1053/j.jvca.2016.03.134. Epub 2016 Mar 16. No abstract available.

Reference Type: BACKGROUND

PMID: 27498260 (View on PubMed)

Thiele RH, Rea KM, Turrentine FE, Friel CM, Hassinger TE, McMurry TL, Goudreau BJ, Umapathi BA, Kron IL, Sawyer RG, Hedrick TL. Standardization of care: impact of an enhanced recovery protocol on length of stay, complications, and direct costs after colorectal surgery. J Am Coll Surg. 2015 Apr;220(4):430-43. doi: 10.1016/j.jamcollsurg.2014.12.042. Epub 2015 Jan 9.

Reference Type: BACKGROUND

PMID: 25797725 (View on PubMed)

Doleman B, Read D, Lund JN, Williams JP. Preventive Acetaminophen Reduces Postoperative Opioid Consumption, Vomiting, and Pain Scores After Surgery: Systematic Review and Meta-Analysis. Reg Anesth Pain Med. 2015 Nov-Dec;40(6):706-12. doi: 10.1097/AAP.0000000000000311.

Reference Type: BACKGROUND

PMID: 26469366 (View on PubMed)

Remy C, Marret E, Bonnet F. Effects of acetaminophen on morphine side-effects and consumption after major surgery: meta-analysis of randomized controlled trials. Br J Anaesth. 2005 Apr;94(4):505-13. doi: 10.1093/bja/aei085. Epub 2005 Jan 28.

Reference Type: BACKGROUND

PMID: 15681586 (View on PubMed)

Macario A, Royal MA. A literature review of randomized clinical trials of intravenous acetaminophen (paracetamol) for acute postoperative pain. Pain Pract. 2011 May-Jun;11(3):290-6. doi: 10.1111/j.1533-2500.2010.00426.x. Epub 2010 Nov 28.

Reference Type: BACKGROUND

PMID: 21114616 (View on PubMed)

Cakan T, Inan N, Culhaoglu S, Bakkal K, Basar H. Intravenous paracetamol improves the quality of postoperative analgesia but does not decrease narcotic requirements. J Neurosurg Anesthesiol. 2008 Jul;20(3):169-73. doi: 10.1097/ANA.0b013e3181705cfb.

Reference Type: BACKGROUND

PMID: 18580346 (View on PubMed)

Brett CN, Barnett SG, Pearson J. Postoperative plasma paracetamol levels following oral or intravenous paracetamol administration: a double-blind randomised controlled trial. Anaesth Intensive Care. 2012 Jan;40(1):166-71. doi: 10.1177/0310057X1204000121.

Reference Type: BACKGROUND

PMID: 22313079 (View on PubMed)

Fenlon S, Collyer J, Giles J, Bidd H, Lees M, Nicholson J, Dulai R, Hankins M, Edelman N. Oral vs intravenous paracetamol for lower third molar extractions under general anaesthesia: is oral administration inferior? Br J Anaesth. 2013 Mar;110(3):432-7. doi: 10.1093/bja/aes387. Epub 2012 Dec 6.

Reference Type: BACKGROUND

PMID: 23220855 (View on PubMed)

Wang S, Saha R, Shah N, Hanna A, DeMuro J, Calixte R, Brathwaite C. Effect of Intravenous Acetaminophen on Postoperative Opioid Use in Bariatric Surgery Patients. P T. 2015 Dec;40(12):847-50.

Reference Type: BACKGROUND

PMID: 26681907 (View on PubMed)

Bameshki A, Peivandi Yazdi A, Sheybani S, Rezaei Boroujerdi H, Taghavi Gilani M. The Assessment of Addition of Either Intravenous Paracetamol or Diclofenac Suppositories to Patient-Controlled Morphine Analgesia for Postgastrectomy Pain Control. Anesth Pain Med. 2015 Oct 10;5(5):e29688. doi: 10.5812/aapm.29688. eCollection 2015 Oct.

Reference Type: BACKGROUND

PMID: 26587407 (View on PubMed)

Strode MA, Sherman W, Mangieri CW, Bland CM, Sparks PJ, Faler BJ, Prasad BM, Choi YU. Randomized trial of OFIRMEV versus placebo for pain management after laparoscopic sleeve gastrectomy. Surg Obes Relat Dis. 2016 May;12(4):772-777. doi: 10.1016/j.soard.2015.08.512. Epub 2015 Aug 29.

Reference Type: BACKGROUND

PMID: 26525369 (View on PubMed)

Saurabh S, Smith JK, Pedersen M, Jose P, Nau P, Samuel I. Scheduled intravenous acetaminophen reduces postoperative narcotic analgesic demand and requirement after laparoscopic Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2015 Mar-Apr;11(2):424-30. doi: 10.1016/j.soard.2014.09.017. Epub 2014 Sep 30.

Reference Type: BACKGROUND

PMID: 25614351 (View on PubMed)

Song K, Melroy MJ, Whipple OC. Optimizing multimodal analgesia with intravenous acetaminophen and opioids in postoperative bariatric patients. Pharmacotherapy. 2014 Dec;34 Suppl 1:14S-21S. doi: 10.1002/phar.1517.

Reference Type: BACKGROUND

PMID: 25521841 (View on PubMed)

Ziolkowski K, Kaufman J, Jambunathan J, Berge J, Menet L, Chappy S, Messerschmidt M. The Clinical Use of Intravenous Acetaminophen Postoperatively on Patients Who Have Undergone Bowel Surgery. AORN J. 2015 Nov;102(5):515.e1-515.e10. doi: 10.1016/j.aorn.2015.09.011.

Reference Type: BACKGROUND

PMID: 26514714 (View on PubMed)

Wininger SJ, Miller H, Minkowitz HS, Royal MA, Ang RY, Breitmeyer JB, Singla NK. A randomized, double-blind, placebo-controlled, multicenter, repeat-dose study of two intravenous acetaminophen dosing regimens for the treatment of pain after abdominal laparoscopic surgery. Clin Ther. 2010 Dec;32(14):2348-69. doi: 10.1016/j.clinthera.2010.12.011.

Reference Type: BACKGROUND

PMID: 21353105 (View on PubMed)

Apfel CC, Turan A, Souza K, Pergolizzi J, Hornuss C. Intravenous acetaminophen reduces postoperative nausea and vomiting: a systematic review and meta-analysis. Pain. 2013 May;154(5):677-689. doi: 10.1016/j.pain.2012.12.025. Epub 2013 Jan 11.

Reference Type: BACKGROUND

PMID: 23433945 (View on PubMed)

Guha A, Scawn ND, Rogers SA, Pennefather SH, Russell GN. Gastric emptying in post-thoracotomy patients receiving a thoracic fentanyl-bupivacaine epidural infusion. Eur J Anaesthesiol. 2002 Sep;19(9):652-7. doi: 10.1017/s0265021502001072.

Reference Type: BACKGROUND

PMID: 12243288 (View on PubMed)

Yuan CS, Foss JF, O'Connor M, Roizen MF, Moss J. Effects of low-dose morphine on gastric emptying in healthy volunteers. J Clin Pharmacol. 1998 Nov;38(11):1017-20. doi: 10.1177/009127009803801105.

Reference Type: BACKGROUND

PMID: 9824782 (View on PubMed)

Jibril F, Sharaby S, Mohamed A, Wilby KJ. Intravenous versus Oral Acetaminophen for Pain: Systematic Review of Current Evidence to Support Clinical Decision-Making. Can J Hosp Pharm. 2015 May-Jun;68(3):238-47. doi: 10.4212/cjhp.v68i3.1458.

Reference Type: BACKGROUND

PMID: 26157186 (View on PubMed)

El Chaar M, Stoltzfus J, Claros L, Wasylik T. IV Acetaminophen Results in Lower Hospital Costs and Emergency Room Visits Following Bariatric Surgery: a Double-Blind, Prospective, Randomized Trial in a Single Accredited Bariatric Center. J Gastrointest Surg. 2016 Apr;20(4):715-24. doi: 10.1007/s11605-016-3088-0. Epub 2016 Feb 2.

Reference Type: BACKGROUND

PMID: 26842692 (View on PubMed)

Apfel CC, Souza K, Portillo J, Dalal P, Bergese SD. Patient satisfaction with intravenous acetaminophen: a pooled analysis of five randomized, placebo-controlled studies in the acute postoperative setting. J Healthc Qual. 2015 May-Jun;37(3):155-62. doi: 10.1111/jhq.12062.

Reference Type: BACKGROUND

PMID: 24433365 (View on PubMed)

Subramaniam K, Esper SA, Mallikarjun K, Dickson A, Ruppert DrPH K, Drabek T, Wong H, Holder-Murray J. The Effect of Scheduled Intravenous Acetaminophen in an Enhanced Recovery Protocol Pathway in Patients Undergoing Major Abdominal Procedures: A Prospective, Randomized, and Placebo-Controlled Clinical Trial. Pain Med. 2022 Jan 3;23(1):10-18. doi: 10.1093/pm/pnab272.

Reference Type: DERIVED

PMID: 34498068 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PRO17050418

Identifier Type: -

Identifier Source: org_study_id