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

Pancreatic Diseases Clinical Trial

Official title:

Role of Scheduled Intravenous Acetaminophen for Postoperative Pain Management in an Enhanced Recovery After Surgery (ERAS) Population: A Prospective, Randomized, Double-Blind and Placebo-Controlled Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03198871
• Other study ID #: PRO17050418
• Status: Completed
• Phase: Phase 4
• Start date: May 24, 2018
• Est. completion date: November 30, 2020

Study information

• Verified date: January 2021
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: November 30, 2020
• Est. primary completion date: July 7, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Abdominal Wall Hernia
• Bowel Disease
• Gastric Disease
• Hernia, Ventral
• Pancreatic Diseases
• Stomach Diseases

Intervention

Drug:
• 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
• 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.

Locations

Country	Name	City	State
United States	Upmc Presbyterian Montefiore Hospital	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Kathirvel Subramaniam	Mallinckrodt

Country where clinical trial is conducted

United States, 

References & Publications (31)

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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. — View Citation

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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.

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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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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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. Epub 2005 Jan 28. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum in: J Am Coll Surg. 2015 May;220(5):986. — View Citation

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. — View Citation

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. — View Citation

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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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Postoperative Pain Intensity	Number of patients with unsatisfactory pain relief defined as average numeric rating scale (NRS) more than 5 will be compared between the two groups. This may include patients using IVPCA for pain relief during the first 48 hours postoperative.	PACU admission every thirty minutes until discharge to the floor and thereafter every four hours for first 24-hour, then every six hours until 48 hours and then every twelve hours until 72 hours postoperatively.
Secondary	Total Post-operative Narcotic Consumption	Rescue analgesia will be given according to institutional pain management protocol. Unit of Measure recorded as OME (Oral Morphine Equivalent) consumption in mg.	From time of PACU admission until the time of discharge and 72-hours postoperatively, whichever comes first
Secondary	Time to Readiness for Discharge From Post Anesthesia Care Unit (PACU)	The time from PACU admission to PACU discharge to the floor will be measured.	From time of PACU admission until the time of discharge, assessed up to 24 hours postoperatively
Secondary	Time to Bowel Movement	The time it takes for the first bowel movement postoperatively will be measured.	From time patient left operating room until the time of first documented bowel movement, assessed up to hospital discharge
Secondary	Time to Oral Intake	The time it takes for the patient to ingest orally post-surgery will be measured.	From date of randomization until the date of first documented oral intake, assessed up to 72 hours postoperatively
Secondary	Time to Ambulation	The time it takes for the patient to successfully ambulate post-surgery will be measured.	From date of PACU admission until the date of first documented ambulation, assessed up to 72 hours postoperatively
Secondary	Time to Hospital Discharge	The time it takes for the patient to be fully discharged from the hospital post-surgery will be measured.	From date of randomization until the date of hospital discharge or 30 days postoperatively, whichever comes first
Secondary	Number of Participants With Readmission to the Hospital	If the patient is readmitted to the hospital after being fully discharged, the event will be recorded.	From the time of consent until 30 days post-operatively
Secondary	Patient Satisfaction	Overall patient satisfaction as well as satisfaction relating to pain management and cost analyses will be measured. These will be measured with a numerical rating scale (NRS) with 0- being worst satisfaction and 10 - best satisfaction.	These measurements will be taken at time of discharge up to 30 days, whichever comes first
Secondary	Intensive Care Delirium Screening Checklist (ICDSC)	Number of patients who score greater than a 4 on the 0-8 point ICDSC scale to assess delirium scores. 8 separate levels of signs for delirium assessed (1. altered level of consciousness, 2. inattention, 3. disorientation, 4. hallucination, delusion, or psychosis, 5. psychomotor agitation or retardation, 6. inappropriate speech or mood, 7. sleep-wake cycle disturbance, 8. symptom fluctuation), with 0 points awarded when patient does not exhibit above signs of delirium and 1 point awarded per confirmed sign of delirium. Score then totaled, 0 = normal, 1-3 = subsyndromal delirium, 4-8 = delirium.	The delirium scores will first be measured every 12 hours for 72 hours after surgery.
Secondary	Post-operative Nausea	Nausea will be evaluated by nausea score from 0 to 10, with 0 equaling no nausea and 10 equaling the worst nausea imaginable.	These will be evaluated from the time of PACU admission until 72 hours postoperatively.
Secondary	Post-operative Emesis	Frequency of emesis and rescue antiemetic requirement will be documented	These will be evaluated from the time of PACU admission until 72 hours postoperatively.
Secondary	SF-12 Health Survey	Survey to assess patient's overall health (via a combination of mental and physical health assessment) at 30 days post-discharge. Two summary scores are reported from the SF-12 - a mental component score (MCS-12) and a physical component score (PCS-12). The scores may be reported as Z-scores (difference compared to the population average, measured in standard deviations). The United States population average PCS-12 and MCS-12 are both 50 points. The United States population standard deviation is 10 points. So each 10 increment of 10 points above or below 50, corresponds to one standard deviation away from the average	These measurements will take place at 30-days post hospital discharge