Clinical trial NCT02775474: Does Intraoperative Methadone Prevent Postoperative Pain in Bariatric Surgery?
Official title: Does Intraoperative Methadone Prevent Postoperative Pain in Bariatric Surgery?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain, Postoperative
Chronic Pain
Keywords: Methadone
Pain, Postoperative
Chronic Pain
Bariatric Surgery
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2016-05-17
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The recent increase in obesity has led to an increase in the need for bariatric surgery. In this group of patients the postoperative pain management is of vital importance. One strategy to improve postoperative analgesia is the use of intraoperative methadone, specially in those patients which regional anesthesia is not feasible. There is evidence that the use of intraoperative methadone can lead to a analgesia lasting 24 to 36 hours, while not associated with increased side effects when compared to other opioids with short or intermediate duration of action. In this study the investigators will evaluate the efficacy of intraoperative methadone in reducing postoperative pain and opioid consumption.

Detailed description: Despite recent developments in postoperative pain control, many patients still suffer from moderate to severe pain after surgery. It is estimated that postoperative severe pain occurs in 20 to 40% of surgical procedures. With the recent increase in obesity incidence in the last years, the need for bariatric surgical intervention is greater. The management of postoperative pain in obese patients is particularly important, since this population have increased susceptibility to cardiovascular, pulmonary and thromboembolic perioperatively.

One of the strategies to improve pain management in the perioperative period is the intraoperative use of intravenous methadone, given its pharmacokinetic profile, specially in those patients in which regional anesthesia is contraindicated. Methadone is an opioid μ (MOR) receptor agonist, also a glutamate antagonist by blocking the N-methyl-D-aspartate (NMDA) receptor and a reuptake of serotonin and noradrenaline inhibitor. Intraoperative analgesia generated by administration of 20 to 30 mg methadone can last 24 to 36 hours. There is also evidence that methadone at 0.2 to 0.3 mg / kg is not associated with an increased incidence of side effects compared to other opioids with short or intermediate duration of action, such as fentanyl, sufentanyl and morphine.

The aim of this study is to evaluate the efficacy of intraoperative methadone in reducing postoperative pain and opioid consumption in patients undergoing open gastroplasty with or without associated Roux Y. Patients will undergo standardized general anesthesia, and the opioid used in anesthesia induction is methadone 0.15 mg / kg fentanyl or 6 mcg / kg bolus with additional if necessary. After extubation a intravenous morphine patient controlled analgesia device will be already available in the operating room. Groups will be compared regarding opioid consumption, pain scores, side effects, patient satisfaction and development of chronic postoperative pain.

Eligibility criteria: Inclusion Criteria:

* Open bariatric surgery
* No contraindications for any drugs used during the trial
* Read, understood and signed the informed consent

Exclusion Criteria:

* Laparoscopic bariatric surgery
* Known allergy to any drugs used during the trial
* Cardiovascular disease
* Creatinine clearance lower than 60 mL/min/1.73 m2
* Chronic usage of opioids
* History of personality disorder

Primary outcomes:
measure: Postoperative Pain
timeFrame: Until 3 months postoperatively
Secondary outcomes:
measure: Postoperative opioid consumption
timeFrame: Until 3 months postoperatively
measure: Side effects
timeFrame: Until 3 months postoperatively
measure: Chronic postoperative pain
timeFrame: 3 months postoperatively
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Hospital das Clínicas da FMUSP
Study officials:
affiliation: University of Sao Paulo General Hospital
name: Claudia Palmeira, MD, PhD
role: STUDY_CHAIR
affiliation: University of Sao Paulo General Hospital
name: Hazem Ashmawi, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Gourlay GK, Wilson PR, Glynn CJ. Methadone produces prolonged postoperative analgesia. Br Med J (Clin Res Ed). 1982 Feb 27;284(6316):630-1. doi: 10.1136/bmj.284.6316.630. No abstract available.
citation: Shaiova L, Berger A, Blinderman CD, Bruera E, Davis MP, Derby S, Inturrisi C, Kalman J, Mehta D, Pappagallo M, Perlov E. Consensus guideline on parenteral methadone use in pain and palliative care. Palliat Support Care. 2008 Jun;6(2):165-76. doi: 10.1017/S1478951508000254.
citation: Toombs JD, Kral LA. Methadone treatment for pain states. Am Fam Physician. 2005 Apr 1;71(7):1353-8.
citation: Kharasch ED. Intraoperative methadone: rediscovery, reappraisal, and reinvigoration? Anesth Analg. 2011 Jan;112(1):13-6. doi: 10.1213/ANE.0b013e3181fec9a3. No abstract available.
citation: Gourlay GK, Willis RJ, Wilson PR. Postoperative pain control with methadone: influence of supplementary methadone doses and blood concentration--response relationships. Anesthesiology. 1984 Jul;61(1):19-26.
citation: Inturrisi CE. Pharmacology of methadone and its isomers. Minerva Anestesiol. 2005 Jul-Aug;71(7-8):435-7.
citation: Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.
citation: Udelsmann A, Maciel FG, Servian DC, Reis E, de Azevedo TM, Melo Mde S. Methadone and morphine during anesthesia induction for cardiac surgery. Repercussion in postoperative analgesia and prevalence of nausea and vomiting. Rev Bras Anestesiol. 2011 Nov-Dec;61(6):695-701. doi: 10.1016/S0034-7094(11)70078-2. English, Multiple languages.
citation: Chui PT, Gin T. A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. Anaesth Intensive Care. 1992 Feb;20(1):46-51. doi: 10.1177/0310057X9202000109.
citation: Richlin DM, Reuben SS. Postoperative pain control with methadone following lower abdominal surgery. J Clin Anesth. 1991 Mar-Apr;3(2):112-6. doi: 10.1016/0952-8180(91)90007-a.
citation: Fernandez AZ Jr, Demaria EJ, Tichansky DS, Kellum JM, Wolfe LG, Meador J, Sugerman HJ. Multivariate analysis of risk factors for death following gastric bypass for treatment of morbid obesity. Ann Surg. 2004 May;239(5):698-702; discussion 702-3. doi: 10.1097/01.sla.0000124295.41578.ab.