The Effect of Ongoing Beta-blockers Administration on Analgesic Requirements in the Immediate Perioperative Period.

Nociceptive Pain Clinical Trial

Official title:

The Effect of Ongoing Beta-blockers Administration on Analgesic Requirements in the Immediate Perioperative Period.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03498898
• Other study ID #: TASMC-17-IM-0598-CTIL
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2018
• Est. completion date: October 1, 2019

Study information

• Verified date: April 2018
• Source: Tel-Aviv Sourasky Medical Center
• Contact: Idit Matot, MD, PhD
• Phone: 97236974758
• Email: iditm[@]tlvmc.gov.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to discover if chronic use of Beta adrenergic receptor blockers affects pain sensation during and after an elective procedure of hip or knee replacement. The study's population will be divided to four groups: Group A- chronic use of Beta adrenergic receptor blockers undergoing total hip replacement, Group B- no use of Beta adrenergic receptor blockers undergoing total hip replacement, Group C- chronic use of Beta adrenergic receptor blockers undergoing total knee replacement and Group D- no use of Beta adrenergic receptor blockers undergoing total knee replacement. Each patient will be anesthetized using the same anesthesia protocol with pain assessment done by the ANI device intra operatively and by NRS score postoperatively.

Description:

The effect of ongoing Beta adrenergic receptor blockers administration on perioperative and post-operative pain.

Beta adrenergic receptor blockers are in common use for treatment of a variety of illnesses. Mostly ones that are connected to the cardiovascular system (such as congestive heart failure, angina pectoris and dysrhythmias) but also for treatment of some neurological disorders and more.

Esmolol and Labetalol are frequently utilized during the perioperative period because of their beneficial effects in treating the acute hemodynamic response to surgical stress. However, clinical studies have confirmed that these adjuvant drugs can reduce postoperative opioid consumption and facilitate earlier extubation. In multiple studies, Esmolol was found effective reducing postoperative pain and the need for narcotic analgesics following surgery. A Meta-analysis published in 2015 in the Journal of Anesthesiology found that Esmolol caused a 32-50% reduction in the need for rescue analgesics and that propranolol decreased the need for rescue analgesics by 72%.

The "Analgesia Nociception Index" (ANI; MetroDoloris Medical Systems, Lille, France), derived from an electrocardiogram (ECG) trace, has been proposed as a noninvasive guide to analgesia. The ANI monitor calculates heart rate variation with respiration, a response mediated primarily by changes in the parasympathetic nervous system (PNS) stimulation to the sinoatrial node of the heart . A painful stimulus will cause a relative decrease in parasympathetic tone and therefore result in a decrease in ANI scores. A score of 100 indicates maximum parasympathetic tone and low nociceptive levels, while a score of zero indicates minimum parasympathetic tone and high nociceptive levels. ANI has been validated in a few studies. In a recently published clinical trial comparing ANI to other predictive modalities and to traditional clinical signs (heart rate and mean arterial pressure) ANI was found to have the highest sensitivity and specificity (P k -0.98) for detecting painful stimulations.

The NRS for pain is a unidimensional measure of pain intensity in adults. The most commonly used is the 11-item NRS which is a segmented numeric version of the visual analog scale (VAS) in which a respondent selects a whole number (0 -10 integers) that best reflects the intensity of their pain where 0 is described as no pain and 10 is described as the worst pain imaginable. The NRS-11 is perhaps the most commonly used pain intensity rating tool with a highly correlated validity to the visual analogue scale (VAS). In addition High test-retest reliability has been observed in both literate and illiterate patients with rheumatoid arthritis (r 0.96 and 0.95, respectively).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: October 1, 2019
• Est. primary completion date: October 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Candidates for an elective hip replacement.

Exclusion Criteria:

• Patients with no sinus rhythm.

• Patients with an internal cardiac device / cardiac pacemaker.

• The use of Anti muscarinic, alpha adrenergic receptor blockers or anti arhythmic medications.

• Chronic use of Opioids (defined as 20 mg or more of Oxycodone per day for a period of 6 weeks or more).

• BMI> 40.

• Sensitivity to one of the following drugs: Propofol, Fentanyl, Rocuronium, Isoflurane, Morphine, Acetaminophen, Ondansetron.

Related Conditions & MeSH terms

• Nociceptive Pain

Intervention

Other:
• Chronic use of Beta adrenergic receptor blocker
Chronic use of Beta adrenergic receptor blocker

Locations

Country	Name	City	State
Israel	Tel-Aviv Sourasky Medical Center	Tel-Aviv

Sponsors (1)

Lead Sponsor	Collaborator
Tel-Aviv Sourasky Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (13)

Andersson V, Bergman S, Henoch I, Wickström Ene K, Otterström-Rydberg E, Simonsson H, Ahlberg K. Pain and pain management in hospitalized patients before and after an intervention. Scand J Pain. 2017 Apr;15:22-29. doi: 10.1016/j.sjpain.2016.11.006. Epub 2016 Dec 9. — View Citation

Chia YY, Chan MH, Ko NH, Liu K. Role of beta-blockade in anaesthesia and postoperative pain management after hysterectomy. Br J Anaesth. 2004 Dec;93(6):799-805. Epub 2004 Sep 17. — View Citation

Collard V, Mistraletti G, Taqi A, Asenjo JF, Feldman LS, Fried GM, Carli F. Intraoperative esmolol infusion in the absence of opioids spares postoperative fentanyl in patients undergoing ambulatory laparoscopic cholecystectomy. Anesth Analg. 2007 Nov;105(5):1255-62, table of contents. — View Citation

De Jonckheere J, Logier R, Jounwaz R, Vidal R, Jeanne M. From pain to stress evaluation using heart rate variability analysis: development of an evaluation platform. Conf Proc IEEE Eng Med Biol Soc. 2010;2010:3852-5. doi: 10.1109/IEMBS.2010.5627661. — View Citation

Dundar N, Kus A, Gurkan Y, Toker K, Solak M. Analgesia nociception index (ani) monitoring in patients with thoracic paravertebral block: a randomized controlled study. J Clin Monit Comput. 2018 Jun;32(3):481-486. doi: 10.1007/s10877-017-0036-9. Epub 2017 Jun 19. — View Citation

Funcke S, Sauerlaender S, Pinnschmidt HO, Saugel B, Bremer K, Reuter DA, Nitzschke R. Validation of Innovative Techniques for Monitoring Nociception during General Anesthesia: A Clinical Study Using Tetanic and Intracutaneous Electrical Stimulation. Anesthesiology. 2017 Aug;127(2):272-283. doi: 10.1097/ALN.0000000000001670. — View Citation

Gruenewald M, Ilies C, Herz J, Schoenherr T, Fudickar A, Höcker J, Bein B. Influence of nociceptive stimulation on analgesia nociception index (ANI) during propofol-remifentanil anaesthesia. Br J Anaesth. 2013 Jun;110(6):1024-30. doi: 10.1093/bja/aet019. Epub 2013 Mar 6. — View Citation

Härkänen L, Halonen J, Selander T, Kokki H. Beta-adrenergic antagonists during general anesthesia reduced postoperative pain: a systematic review and a meta-analysis of randomized controlled trials. J Anesth. 2015 Dec;29(6):934-43. doi: 10.1007/s00540-015-2041-9. Epub 2015 Jul 10. Review. — View Citation

Jensen MP, McFarland CA. Increasing the reliability and validity of pain intensity measurement in chronic pain patients. Pain. 1993 Nov;55(2):195-203. — View Citation

Logier R, Jeanne M, De Jonckheere J, Dassonneville A, Delecroix M, Tavernier B. PhysioDoloris: a monitoring device for analgesia / nociception balance evaluation using heart rate variability analysis. Conf Proc IEEE Eng Med Biol Soc. 2010;2010:1194-7. doi: 10.1109/IEMBS.2010.5625971. — View Citation

López-Álvarez S, Mayo-Moldes M, Zaballos M, Iglesias BG, Blanco-Dávila R. Esmolol versus ketamine-remifentanil combination for early postoperative analgesia after laparoscopic cholecystectomy: a randomized controlled trial. Can J Anaesth. 2012 May;59(5):442-8. doi: 10.1007/s12630-012-9684-x. Epub 2012 Mar 2. — View Citation

Upton HD, Ludbrook GL, Wing A, Sleigh JW. Intraoperative "Analgesia Nociception Index"-Guided Fentanyl Administration During Sevoflurane Anesthesia in Lumbar Discectomy and Laminectomy: A Randomized Clinical Trial. Anesth Analg. 2017 Jul;125(1):81-90. doi: 10.1213/ANE.0000000000001984. — View Citation

White PF. What are the advantages of non-opioid analgesic techniques in the management of acute and chronic pain? Expert Opin Pharmacother. 2017 Mar;18(4):329-333. doi: 10.1080/14656566.2017.1289176. Epub 2017 Feb 20. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fentanyl consumption during surgery.	Measuring the effect of chronic use of Beta adrenergic receptor blockers on the amount of analgesia (Fentanyl).	Intra operative (anaesthesia start until anaesthesia end).
Secondary	Post operative Morphine consumption.	Measuring the effect of chronic use of Beta adrenergic receptor blockers on the amount of analgesia (Morphine).	Immediate post operative time (from admission to release from PACU).
Secondary	Post operative non opioid analgesia consumption.	Measuring the effect of chronic use of Beta adrenergic receptor blockers on the amount of non opioid analgesia.	Immediate post operative time (from admission to release from PACU).
Secondary	Post operative pain (NRS score).	Measuring the effect of chronic use of Beta adrenergic receptor blockers on NRS pain score.	15 minutes after admission to PACU.