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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Nociceptive Pain

Intervention / Treatment
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* Other: Chronic use of Beta adrenergic receptor blocker


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>American Society of Anesthesiologists (ASA) Score 2-3 with chronic use of Beta adrenergic receptor blockers planned to undergo total hip replacement | Other: Chronic use of Beta adrenergic receptor blocker<br>* Chronic use of Beta adrenergic receptor blocker<br>|
| No Intervention: Group B<br>American Society of Anesthesiologists (ASA) Score 2-3 with no chronic use of Beta adrenergic receptor blockers planned to undergo total hip replacement | |
| Active Comparator: Group C<br>American Society of Anesthesiologists (ASA) Score 2-3 with chronic use of Beta adrenergic receptor blockers planned to undergo total knee replacement. | Other: Chronic use of Beta adrenergic receptor blocker<br>* Chronic use of Beta adrenergic receptor blocker<br>|
| No Intervention: Group D<br>American Society of Anesthesiologists (ASA) Score 2-3 with no chronic use of Beta adrenergic receptor blockers planned to undergo total knee replacement | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 
| 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). | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Beta adrenergic receptor blockers, Analgesia nociceptive index, Total hip replacement, Total knee replacement