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No funding source
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| Name | Class |
|---|---|
| Foundation for Anesthesia Education and Research | OTHER |
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The purpose of this study is to determine if treatment with low-dose oral propranolol in the days before and after surgery decrease postoperative pain and improve pain scores.
This study is a randomized, double-blind, placebo controlled clinical trial.The main purpose of this study is to determine if postsurgical opioid use and pain scores are decreased with oral Propranolol treatment. The treatment period will last for six days and the observation period will last for three months. Effectiveness of treatment will be assessed by means of post-operative opioid consumption as primary outcome measure.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Propranolol treatment | Experimental | Subjects randomized to the propranolol treatment arm will be administered propranolol 40mg BID for three days prior to surgery, 40mg BID the day of surgery and on post-operative days 1 and 2. Subjects and researchers will be blinded and will not know if propranolol or placebo control is administered. Patients will be evaluated for opioid usend pain scores at 24 hrs, 48 hrs, 1 week, 4 weeks, and 12 weeks post-op. Blood will also be obtained pre-operatively, 8 hours and 24 hours post-operatively to measure the level of inflammatory markers. We will use these samples to evaluate if treatment with propranolol decreases the levels of inflammatory markers, and if this correlates to decreased opioid use and pain scores post-operatively. All other pre-, intra-, and post-operative interventions will be equivalent between the experimental and placebo groups, and this study's interventions will not affect surgical management. |
|
| Placebo | Placebo Comparator | Subjects randomized to the placebo treatment arm will be administered placebo tablets with the same schedule as propranolol in the experimental arm. Subjects and researchers will be blinded and will not know if propranolol or placebo control is administered. Patients will be evaluated for opioid use and pain scores at 24 hrs, 48 hrs, 1 week, 4 weeks, and 12 weeks post-op. Blood will also be obtained pre-operatively, 8 hours and 24 hours post-operatively to measure the level of inflammatory markers. We will use these samples to evaluate if treatment with propranolol decreases the levels of inflammatory markers compared to placebo, and if this correlates to decreased opioid use and pain scores post-operatively. All other pre-, intra-, and post-operative interventions will be equivalent between the experimental and placebo groups, and this study's interventions will not affect surgical management. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propranolol Hcl 40mg Tab | Drug | 40mg PO BID for the three days prior to surgery, 40mg PO BID the day of surgery and on post-op days 1 and 2. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Acute postoperative opioid use at 24 hours | Total opioid use from 0 to 24 hours post-op will be quantified. Opioid doses administered via all routes will be converted to standard oral morphine equivalents (OME). | 24 hours postoperatively |
| Measure | Description | Time Frame |
|---|---|---|
| Acute postoperative opioid use at 48 hours | Total opioid use from 24 to 48 hours post-op will be quantified. Opioid doses administered via all routes will be converted to standard oral morphine equivalents (OME). | 48 hours postoperatively |
| Sub-acute postoperative opioid use at 1 week |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Buchheit, MD | Department of Anesthesiology, Duke University | Principal Investigator |
| Stephan Frangakis, MD/PhD | Department of Anesthesiology, Duke University | Study Director |
| William Maixner, DDS/PhD | Department of Anesthesiology, Duke University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Hospital | Durham | North Carolina | 27710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29209205 | Background | Afify EA, Andijani NM. Potentiation of Morphine-Induced Antinociception by Propranolol: The Involvement of Dopamine and GABA Systems. Front Pharmacol. 2017 Nov 10;8:794. doi: 10.3389/fphar.2017.00794. eCollection 2017. | |
| 26950706 | Background | Ciszek BP, O'Buckley SC, Nackley AG. Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral beta-Adrenergic Receptors. Anesthesiology. 2016 May;124(5):1122-35. doi: 10.1097/ALN.0000000000001070. |
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| ID | Term |
|---|---|
| C535531 | Intervertebral disc disease |
| D055959 | Intervertebral Disc Degeneration |
| D010149 | Pain, Postoperative |
| ID | Term |
|---|---|
| D013122 | Spinal Diseases |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D011183 | Postoperative Complications |
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| D005947 | Glucose |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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| Placebo oral tablet | Drug | Placebo tablets administered with the same schedule of Propranolol tablets |
|
|
Patient reported current opioid use for the prior 24 hours will be quantified at 1 week post-op. Opioid use will be converted to standard oral morphine equivalents (OME). |
| 1 week postoperatively |
| Sub-acute postoperative opioid use at 4 weeks | Patient reported current opioid use for the prior 24 hours will be quantified at 4 weeks post-op. Opioid use will be converted to standard oral morphine equivalents (OME). | 4 weeks postoperatively |
| Sub-acute postoperative opioid use at 12 weeks | Patient reported current opioid use for the prior 24 hours will be quantified at 12 weeks post-op. Opioid use will be converted to standard oral morphine equivalents (OME). | 12 weeks postoperatively |
| Acute postoperative pain scores at 24 hours | The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 24 post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome. | 24 hours post-op |
| Acute postoperative pain scores at 48 hours | The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 48 hours post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome. | 48 hours post-op |
| Sub-acute postoperative pain scores at 1 week | The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 1 week post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome. | 1 week postoperatively |
| Sub-acute postoperative pain scores at 4 weeks | The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 4 week post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome. | 4 weekspostoperatively |
| Sub-acute postoperative pain scores at 12 weeks | The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 12 weeks post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome. | 12 weeks postoperatively |
| 24237004 | Background | Gan TJ, Habib AS, Miller TE, White W, Apfelbaum JL. Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey. Curr Med Res Opin. 2014 Jan;30(1):149-60. doi: 10.1185/03007995.2013.860019. Epub 2013 Nov 15. |
| 24727346 | Background | Hartung JE, Ciszek BP, Nackley AG. beta2- and beta3-adrenergic receptors drive COMT-dependent pain by increasing production of nitric oxide and cytokines. Pain. 2014 Jul;155(7):1346-1355. doi: 10.1016/j.pain.2014.04.011. Epub 2014 Apr 13. |
| 16698416 | Background | Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X. |
| 19418100 | Background | Krebs EE, Lorenz KA, Bair MJ, Damush TM, Wu J, Sutherland JM, Asch SM, Kroenke K. Development and initial validation of the PEG, a three-item scale assessing pain intensity and interference. J Gen Intern Med. 2009 Jun;24(6):733-8. doi: 10.1007/s11606-009-0981-1. Epub 2009 May 6. |
| 19411061 | Background | Light KC, Bragdon EE, Grewen KM, Brownley KA, Girdler SS, Maixner W. Adrenergic dysregulation and pain with and without acute beta-blockade in women with fibromyalgia and temporomandibular disorder. J Pain. 2009 May;10(5):542-52. doi: 10.1016/j.jpain.2008.12.006. |
| 17084978 | Background | Nackley AG, Tan KS, Fecho K, Flood P, Diatchenko L, Maixner W. Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors. Pain. 2007 Apr;128(3):199-208. doi: 10.1016/j.pain.2006.09.022. Epub 2006 Nov 7. |
| 30021647 | Background | Page MG, Kudrina I, Zomahoun HTV, Ziegler D, Beaulieu P, Charbonneau C, Cogan J, Daoust R, Martel MO, Neron A, Richebe P, Clarke H. Relative frequency and risk factors for long-term opioid therapy following surgery and trauma among adults: a systematic review protocol. Syst Rev. 2018 Jul 18;7(1):97. doi: 10.1186/s13643-018-0760-3. |
| 6213289 | Background | Stanley TH, de Lange S, Boscoe MJ, de Bruijn N. The influence of chronic preoperative propranolol therapy on cardiovascular dynamics and narcotic requirements during operation in patients with coronary artery disease. Can Anaesth Soc J. 1982 Jul;29(4):319-24. doi: 10.1007/BF03007519. |
| 20216107 | Background | Tchivileva IE, Lim PF, Smith SB, Slade GD, Diatchenko L, McLean SA, Maixner W. Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study. Pharmacogenet Genomics. 2010 Apr;20(4):239-48. doi: 10.1097/FPC.0b013e328337f9ab. |
| Background | Teimoori, B., Khoshfetrat, M., Beyrami, F., Sakhavar, N., Dehbashi, Z., Narouie, B., & Davarian, A. Propranolol decreases the post-operative pain and analgesic administration following abdominal hysterectomy. Life Sciences Journal 9: 1216-1220, 2012. |
| 29226500 | Background | Zanelatto FB, Dias EV, Teixeira JM, Sartori CR, Parada CA, Tambeli CH. Anti-inflammatory effects of propranolol in the temporomandibular joint of female rats and its contribution to antinociceptive action. Eur J Pain. 2018 Mar;22(3):572-582. doi: 10.1002/ejp.1143. Epub 2017 Dec 11. |
| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D006601 | Hexoses |
| D009005 | Monosaccharides |
| D000073893 | Sugars |
| D002241 | Carbohydrates |