<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03809949</url>
  </required_header>
  <id_info>
    <org_study_id>050108073(18/12/2018)</org_study_id>
    <nct_id>NCT03809949</nct_id>
  </id_info>
  <brief_title>Opioid Free Versus Opioid Balanced Anesthesia</brief_title>
  <official_title>Opioid Free Versus Opioid Balanced Anesthesia in Middle Ear Surgery.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alexandria</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Alexandria</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      OPIOID FREE VERSUS OPIOID BALANCED ANAESTHESIA IN MIDDLE EAR SURGERY AIM OF THE WORK&#xD;
&#xD;
      Primary aim:&#xD;
&#xD;
      To compare between opioid and opioid free anaesthesia on post-operative nausea and vomiting&#xD;
      in middle ear surgery&#xD;
&#xD;
      Secondary aim:&#xD;
&#xD;
      Monitoring analgesia, post-operative satisfaction and drowsiness.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After approval of the Ethical Committee of Faculty of Medicine, Alexandria University and&#xD;
      having an informed written consent from every patient included in the study, the present&#xD;
      study will be carried out in Alexandria Main University Hospitals on sixty adult patients&#xD;
      belonging to ASA class I or II scheduled for middle ear surgery under general anaesthesia.&#xD;
&#xD;
      (The sample size is approved to be sufficient by the Department of Statistics, Medical&#xD;
      Research Institute, University of Alexandria).&#xD;
&#xD;
      Inclusion criteria:&#xD;
&#xD;
        -  Patients of either sex.&#xD;
&#xD;
        -  American Society Anesthesiologists' physical status I-II.&#xD;
&#xD;
        -  Age between 18 and 50 years. Exclusion criteria:(depend on table 1)&#xD;
&#xD;
        -  Patients with gastrointestinal disease.&#xD;
&#xD;
        -  A history of motion sickness, or a previous episode of PONV.&#xD;
&#xD;
        -  Patient received any opioid, steroid, or antiemetic medication within 72 h before&#xD;
           surgery.&#xD;
&#xD;
        -  Those who were pregnant or menstruating.&#xD;
&#xD;
        -  History of opioid or drug abuse. METHODS Patients will be randomly allocated into two&#xD;
           equal groups (thirty patients each) using the closed envelope method.&#xD;
&#xD;
      I will compare postoperative nausea and vomiting (PONV) in patients scheduled for middle ear&#xD;
      surgery. Sixty patients will be randomly allocated to receive either balanced anaesthesia&#xD;
      (group A) using fentanyl, propofol and isoflurane, or opioid free anaesthesia (group B) using&#xD;
      propofol and isoflurane. Pain scores, nausea ⁄ vomiting scores, conditions for surgery and&#xD;
      analgesic requirements will be recorded post operatively.&#xD;
&#xD;
      Anaesthetic management Preoperative management&#xD;
&#xD;
      All patients will be visited before surgery to be clinically assessed and the preoperative&#xD;
      surveillance includes:&#xD;
&#xD;
        -  Haematological screening (Complete blood picture, Serum electrolytes).&#xD;
&#xD;
        -  Standard coagulation studies e.g. prothrombin time, international normalized ratio&#xD;
           (PT-INR).&#xD;
&#xD;
      On arrival to the operating room and before anaesthetic induction all patients will be&#xD;
      monitored by the standard routine monitoring, which include:&#xD;
&#xD;
        -  A 5-lead electrocardiography.&#xD;
&#xD;
        -  A non-invasive blood pressure (NIBP) (mmHg).&#xD;
&#xD;
        -  Pulse oximetry (%).&#xD;
&#xD;
        -  Capnography. (End Tidal CO2 pattern and value in mmHg).&#xD;
&#xD;
        -  Temperature monitoring. A peripheral intravenous cannula of 20 gauges will be inserted&#xD;
           in a dorsal vein of the non-dominant hand.&#xD;
&#xD;
      Premedication with Midazolam in a dose of 0.02mg/ Kg will be used. Induction Preoxygenation&#xD;
      with 100 % O2 for 3 minutes. General anaesthesia will be induced by propofol (2 mg/kg) and&#xD;
      atracurium (0.5 mg/kg) intravenously guided by a nerve stimulator, followed by endotracheal&#xD;
      intubation after loss of train of four.&#xD;
&#xD;
      All the patients will receive i.v. acetaminophen (1000 mg) _20 min after induction and i.v.&#xD;
      ketorolac (30 mg).&#xD;
&#xD;
      Local analgesia will be injected by surgeon. All patients will receive beta blocker (Inderal&#xD;
      1mg) and magnesium sulphate (15-30mg/kg) for achieving hypotensive anaesthesia.&#xD;
&#xD;
      Maintenance Maintenance of general anaesthesia with a mixture of isoflurane (1MAC) and&#xD;
      oxygen.&#xD;
&#xD;
      All patients will be mechanically ventilated with an anaesthesia machine to keep SpO2 &gt; 95%&#xD;
      and end-tidal CO2 between 35-45 mmHg.&#xD;
&#xD;
      Additional atracurium will be administrated as appropriate in bolus doses if needed.&#xD;
&#xD;
      Group A Fentanyl (1mg/kg i.v.) will be administered before general anaesthesia (GA). GA will&#xD;
      be maintained with inhalation anaesthetics (isoflurane) at a minimum alveolar concentration&#xD;
      of 0.7-1.3.&#xD;
&#xD;
      Group B Opioid free anesthesia (syringe of saline is given instead of fentanyl) and the same&#xD;
      general anesthesia is given as group A(muscle relaxant ,propofol, inhalation for maintance).&#xD;
&#xD;
      Recovery At the end of surgery, isoflurane will be discontinued, 100% oxygen will be given,&#xD;
      all patients will be planned for extubation in the operating room depending on recovery&#xD;
      criteria after complete reversal of muscle relaxant with neostigmine (up to 5 mg).&#xD;
&#xD;
      Tracheal extubation will be performed in a semi- sitting position after fulfilling the&#xD;
      criteria for extubation. Extubation criteria include: a fully conscious patient, haemodynamic&#xD;
      stability, reversal of neuromuscular blockade, TOF ratio 0.9 - 1 on nerve stimulator, and the&#xD;
      ability of head lift for 5 seconds.&#xD;
&#xD;
      Postoperative multimodal pain management Postoperative pain will be treated with i.v.&#xD;
      acetaminophen (1000mg) and i.v. ketorolac (30 mg) every 6 h for the first 24 h. Postoperative&#xD;
      pain will be measured on an 11-point numeric pointscale (NPS).&#xD;
&#xD;
      management of PONV Dexamethasone (8 mg i.v.) will be administered during induction,&#xD;
      ondansetron (4 mg i.v.) and metoclopramide (10 mg i.v.) post operative if Patients&#xD;
      complaining of PONV after discharge from the PACU.&#xD;
&#xD;
      Measurements&#xD;
&#xD;
        1. Demographic data:&#xD;
&#xD;
           Age (years), sex, weight (kilograms).&#xD;
&#xD;
        2. Hemodynamic parameters:&#xD;
&#xD;
             -  Pulse oximetry (%)&#xD;
&#xD;
             -  Heart rate (HR). Beats/minute&#xD;
&#xD;
             -  Mean Non-Invasive arterial blood pressure (NIBP) (mmHg)&#xD;
&#xD;
        3. Pain assessment The level of pain will be assessed on an 11-point NPS. Patients will be&#xD;
           asked to determine their own 'acceptable' pain score.&#xD;
&#xD;
           The 11-point numeric scale ranges from '0' representing no pain extreme to '10'&#xD;
           representing the other pain extreme (worst pain imaginable).(8)&#xD;
&#xD;
        4. Nausea and vomiting assessment (table2,3) Patients will be asked to rate the worst&#xD;
           episode of PONV on a four-point verbal rating scale (VRS) (none, mild, moderate, or&#xD;
           severe). Patients were also will be asked whether they experienced retching or vomiting.&#xD;
&#xD;
        5. Sedation assessment&#xD;
&#xD;
      Sedation score:&#xD;
&#xD;
      0. Alert&#xD;
&#xD;
        1. Mild, drowsy, easy to awake&#xD;
&#xD;
        2. Moderate, easy to arouse&#xD;
&#xD;
        3. Severe: somnolent difficult to arouse&#xD;
&#xD;
        4. Sleeping The Sedation score will be documented at 0, 1, 2, 4, 6, 12, 18, and 24 hours.&#xD;
&#xD;
      6. Satsifacation of patient assessment by QoR40 questionnaire The QoR-40 is a global measure&#xD;
      of quality of recovery. It incorporates five dimensions: patient support, comfort, emotions,&#xD;
      physical independence, and pain; each item is graded on a five-point Likert scale. QoR-40&#xD;
      scores range from 40 (extremely poor quality of recovery) to 200 (excellent quality of&#xD;
      recovery).(29) Timing Hemodynamic (blood pressure, pulse) of Patients will be assessed during&#xD;
      the surgery every 10 minutes and at 1 and 2 h after the end of surgery and at discharge from&#xD;
      the day unit. At each of these times, the nurse recorded the incidence and worst severity of&#xD;
      pain, nausea and emesis since the last evaluation using the same criteria as before. Any&#xD;
      medication will be given for pain or nausea (administered for moderate-severe symptoms, or at&#xD;
      patient request) will be also recorded, till the time of discharge. Patients will be&#xD;
      discharged with medication comprising slow-release ibuprofen. The following day, the&#xD;
      researcher will telephone the patient to assess the incidence and worst severity of pain,&#xD;
      nausea and emesis since discharge and whether any analgesia or antiemetics will be taken.&#xD;
      Patients will be also asked to record their satisfaction with the control of pain, the&#xD;
      control of sickness and their overall day surgery experience on 11-point (0-10) verbal rating&#xD;
      scales.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 16, 2019</start_date>
  <completion_date type="Actual">May 22, 2019</completion_date>
  <primary_completion_date type="Actual">May 21, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>To compare between opioid and opioid free anaesthesia on post-operative nausea and vomiting in middle ear surgery</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    <masking_description>Doctors, patients and outcomes assessors will be blinded regarding the technique used in anesthesia.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>PONV</measure>
    <time_frame>72 hours</time_frame>
    <description>Post operative nausea and vomiting from 0-3 for nausea and 0 to 4 for vomiting</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>analgesia.post-operative pain</measure>
    <time_frame>72 hours</time_frame>
    <description>analgesia, post-operative VAS score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction</measure>
    <time_frame>72 hours</time_frame>
    <description>satisfaction degree by QoR40 questionnaire from 40 to 200</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drowsiness</measure>
    <time_frame>72 hours</time_frame>
    <description>Drowsiness scores by RAMSY sedation score from 0 to 4</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>PONV</condition>
  <condition>Opioid Use</condition>
  <arm_group>
    <arm_group_label>Fentanyl Opioid Anesthesia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Fentanyl (1mg/kg i.v.) will be administered before general anaesthesia (GA). GA will be maintained with inhalation anaesthetics (isoflurane) at a minimum alveolar concentration of 0.7-1.3.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline Nonopioid Anesthesia</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Opioid free anesthesia (syringe of saline is given instead of fentanyl) and the same general anesthesia is given as group A(muscle relaxant ,propofol, inhalation for maintance).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl Opioid anesthesia</intervention_name>
    <description>To compare between opioid and opioid free anaesthesia on post-operative nausea and vomiting in middle ear surgery</description>
    <arm_group_label>Fentanyl Opioid Anesthesia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline Nonopioid anesthesia</intervention_name>
    <description>To compare between opioid and opioid free anaesthesia on post-operative nausea and vomiting in middle ear surgery</description>
    <arm_group_label>Saline Nonopioid Anesthesia</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients of either sex.&#xD;
&#xD;
          -  American Society Anesthesiologists' physical status I-II.&#xD;
&#xD;
          -  Age between 18 and 50 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with gastrointestinal disease.&#xD;
&#xD;
          -  A history of motion sickness, or a previous episode of PONV.&#xD;
&#xD;
          -  Patient received any opioid, steroid, or antiemetic medication within 72 h before&#xD;
             surgery.&#xD;
&#xD;
          -  Those who were pregnant or menstruating.&#xD;
&#xD;
          -  History of opioid or drug abuse.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Alexandria Faculty of Medicine</name>
      <address>
        <city>Alexandria</city>
        <zip>21111</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Quemby DJ. Day surgery development and practice: key factors for a successful pathway. CEACCP 2014;14: 256-61.</citation>
  </reference>
  <reference>
    <citation>Moore KL, Dalley AF. Clinically orientated anatomy. 4th ed. Philadelphia: Lippinocott Williams &amp; Wilkins; 1999.</citation>
  </reference>
  <reference>
    <citation>Dhillon RS, East CA. Ear, nose, throat, and head and neck surgery: an illustrated colored text. 2nd ed. New York, Edinburgh: Churchill Livingstone;1999</citation>
  </reference>
  <reference>
    <citation>Deacock AR. Aspects of anaesthesia for middle ear surgery an blood loss during stapedectomy. Proc R Soc Med. 1971 Dec;64(12):1226-8. No abstract available.</citation>
    <PMID>4399792</PMID>
  </reference>
  <reference>
    <citation>Miller RD. Miller's anesthesia, 6th ed. Vol 2. New York: Elsevier/Churchill Livingstone; 2005.</citation>
  </reference>
  <reference>
    <citation>Morgan EG, Mikhail MS, Murray MJ. Clinical anesthesiology. 4th ed. New York: Lange Medical Books/McGraw-Hill; 2006.</citation>
  </reference>
  <reference>
    <citation>Bailey CR. Management of outpatient ear, nose and throat surgery. Curr Opin Anaesthesiol. 2001 Dec;14(6):617-21. doi: 10.1097/00001503-200112000-00003.</citation>
    <PMID>17019154</PMID>
  </reference>
  <reference>
    <citation>Honkavaara P, Saarnivaara L, Klemola UM. Prevention of nausea and vomiting with transdermal hyoscine in adults after middle ear surgery during general anaesthesia. Br J Anaesth. 1994 Dec;73(6):763-6. doi: 10.1093/bja/73.6.763.</citation>
    <PMID>7880660</PMID>
  </reference>
  <reference>
    <citation>Fujii Y, Toyooka H, Tanaka H. Prophylactic antiemetic therapy with a combination of granisetron and dexamethasone in patients undergoing middle ear surgery. Br J Anaesth. 1998 Nov;81(5):754-6. doi: 10.1093/bja/81.5.754.</citation>
    <PMID>10193289</PMID>
  </reference>
  <reference>
    <citation>Fujii Y, Saitoh Y, Tanaka H, Toyooka H. Anti-emetic efficacy of prophylactic granisetron compared with perphenazine for the prevention of post-operative vomiting in children. Eur J Anaesthesiol. 1999 May;16(5):304-7. doi: 10.1046/j.1365-2346.1999.00483.x.</citation>
    <PMID>10390665</PMID>
  </reference>
  <reference>
    <citation>Gombar S, Kaur J, Kumar Gombar K, Dass A, Singh A. Superior anti-emetic efficacy of granisetron-dexamethasone combination in children undergoing middle ear surgery. Acta Anaesthesiol Scand. 2007 May;51(5):621-4. doi: 10.1111/j.1399-6576.2007.01296.x.</citation>
    <PMID>17430326</PMID>
  </reference>
  <reference>
    <citation>Bovill JG, Sebel PS, Stanley TH. Opioid analgesics in anesthesia: with special reference to their use in cardiovascular anesthesia. Anesthesiology. 1984 Dec;61(6):731-55.</citation>
    <PMID>6150663</PMID>
  </reference>
  <reference>
    <citation>Long DR, Lihn AL, Friedrich S, Scheffenbichler FT, Safavi KC, Burns SM, Schneider JC, Grabitz SD, Houle TT, Eikermann M. Association between intraoperative opioid administration and 30-day readmission: a pre-specified analysis of registry data from a healthcare network in New England. Br J Anaesth. 2018 May;120(5):1090-1102. doi: 10.1016/j.bja.2017.12.044. Epub 2018 Mar 9.</citation>
    <PMID>29661386</PMID>
  </reference>
  <reference>
    <citation>Golembiewski J, Chernin E, Chopra T. Prevention and treatment of postoperative nausea and vomiting. Am J Health Syst Pharm. 2005 Jun 15;62(12):1247-60; quiz 1261-2. doi: 10.1093/ajhp/62.12.1247.</citation>
    <PMID>15947124</PMID>
  </reference>
  <reference>
    <citation>Macario A, Weinger M, Truong P, Lee M. Which clinical anesthesia outcomes are both common and important to avoid? The perspective of a panel of expert anesthesiologists. Anesth Analg. 1999 May;88(5):1085-91. doi: 10.1097/00000539-199905000-00023.</citation>
    <PMID>10320175</PMID>
  </reference>
  <reference>
    <citation>Smith I, Terhoeve PA, Hennart D, Feiss P, Harmer M, Pourriat JL, Johnson IA. A multicentre comparison of the costs of anaesthesia with sevoflurane or propofol. Br J Anaesth. 1999 Oct;83(4):564-70. doi: 10.1093/bja/83.4.564.</citation>
    <PMID>10673870</PMID>
  </reference>
  <reference>
    <citation>Smith I, Thwaites AJ. Target-controlled propofol vs. sevoflurane: a double-blind, randomised comparison in day-case anaesthesia. Anaesthesia. 1999 Aug;54(8):745-52. doi: 10.1046/j.1365-2044.1999.00953.x.</citation>
    <PMID>10460526</PMID>
  </reference>
  <reference>
    <citation>Fleischmann E, Akca O, Wallner T, Arkilic CF, Kurz A, Hickle RS, Zimpfer M, Sessler DI. Onset time, recovery duration, and drug cost with four different methods of inducing general anesthesia. Anesth Analg. 1999 Apr;88(4):930-5. doi: 10.1097/00000539-199904000-00046.</citation>
    <PMID>10195551</PMID>
  </reference>
  <reference>
    <citation>Fredman B, Nathanson MH, Smith I, Wang J, Klein K, White PF. Sevoflurane for outpatient anesthesia: a comparison with propofol. Anesth Analg. 1995 Oct;81(4):823-8. doi: 10.1097/00000539-199510000-00028.</citation>
    <PMID>7574017</PMID>
  </reference>
  <reference>
    <citation>Shakir AAK, Ramachandra V, Hasan MA. Day surgery postoperative nausea and vomiting at home related to preoperative fentanyl. J One-day Surg 1997;6:10-1.</citation>
  </reference>
  <reference>
    <citation>Apfel CC, Laara E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology. 1999 Sep;91(3):693-700. doi: 10.1097/00000542-199909000-00022.</citation>
    <PMID>10485781</PMID>
  </reference>
  <reference>
    <citation>Vandermeulen EP. Controlling the stress response. In: White PF (ed). Textbook of Intravenous Anesthesia. Baltimore: Williams &amp; Wilkins; 1997. p. 565-79.</citation>
  </reference>
  <reference>
    <citation>Borgeat A, Wilder-Smith OH, Saiah M, Rifat K. Subhypnotic doses of propofol possess direct antiemetic properties. Anesth Analg. 1992 Apr;74(4):539-41. doi: 10.1213/00000539-199204000-00013.</citation>
    <PMID>1554120</PMID>
  </reference>
  <reference>
    <citation>Gan TJ, Glass PSA. Balanced anesthesia. In: White PF (ed). Textbook of Intravenous Anesthesia. Baltimore: Williams &amp; Wilkins; 1997. p. 347-74.</citation>
  </reference>
  <reference>
    <citation>Smith I. Inhalational anesthetic agents. In: Hemmings HC, Hopkins PM (eds). Foundations of Anesthesia. 2nd ed. London: Elsevier; 2005. p. 311-21.</citation>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>24554545</PMID>
  </reference>
  <reference>
    <citation>Bakan M, Umutoglu T, Topuz U, Uysal H, Bayram M, Kadioglu H, Salihoglu Z. Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double-blinded study. Braz J Anesthesiol. 2015 May-Jun;65(3):191-9. doi: 10.1016/j.bjane.2014.05.001. Epub 2014 Jun 3.</citation>
    <PMID>25925031</PMID>
  </reference>
  <reference>
    <citation>Feld JM, Hoffman WE, Stechert MM, Hoffman IW, Ananda RC. Fentanyl or dexmedetomidine combined with desflurane for bariatric surgery. J Clin Anesth. 2006 Feb;18(1):24-8. doi: 10.1016/j.jclinane.2005.05.009.</citation>
    <PMID>16517328</PMID>
  </reference>
  <reference>
    <citation>Gornall BF, Myles PS, Smith CL, Burke JA, Leslie K, Pereira MJ, Bost JE, Kluivers KB, Nilsson UG, Tanaka Y, Forbes A. Measurement of quality of recovery using the QoR-40: a quantitative systematic review. Br J Anaesth. 2013 Aug;111(2):161-9. doi: 10.1093/bja/aet014. Epub 2013 Mar 6.</citation>
    <PMID>23471753</PMID>
  </reference>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>July 9, 2019</last_update_submitted>
  <last_update_submitted_qc>July 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Alexandria</investigator_affiliation>
    <investigator_full_name>Mohammad Hazem I. Ahmad Sabry</investigator_full_name>
    <investigator_title>Lecturer of Anesthesia</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Anesthetics</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03809949
org study id: 050108073(18/12/2018)
nct id: NCT03809949
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
OPIOID FREE VERSUS OPIOID BALANCED ANAESTHESIA IN MIDDLE EAR SURGERY AIM OF THE WORK

      Primary aim:

      To compare between opioid and opioid free anaesthesia on post-operative nausea and vomiting
      in middle ear surgery

      Secondary aim:

      Monitoring analgesia, post-operative satisfaction and drowsiness.
After approval of the Ethical Committee of Faculty of Medicine, Alexandria University and
      having an informed written consent from every patient included in the study, the present
      study will be carried out in Alexandria Main University Hospitals on sixty adult patients
      belonging to ASA class I or II scheduled for middle ear surgery under general anaesthesia.

      (The sample size is approved to be sufficient by the Department of Statistics, Medical
      Research Institute, University of Alexandria).

      Inclusion criteria:

        -  Patients of either sex.

        -  American Society Anesthesiologists' physical status I-II.

        -  Age between 18 and 50 years. Exclusion criteria:(depend on table 1)

        -  Patients with gastrointestinal disease.

        -  A history of motion sickness, or a previous episode of PONV.

        -  Patient received any opioid, steroid, or antiemetic medication within 72 h before
           surgery.

        -  Those who were pregnant or menstruating.

        -  History of opioid or drug abuse. METHODS Patients will be randomly allocated into two
           equal groups (thirty patients each) using the closed envelope method.

      I will compare postoperative nausea and vomiting (PONV) in patients scheduled for middle ear
      surgery. Sixty patients will be randomly allocated to receive either balanced anaesthesia
      (group A) using fentanyl, propofol and isoflurane, or opioid free anaesthesia (group B) using
      propofol and isoflurane. Pain scores, nausea ⁄ vomiting scores, conditions for surgery and
      analgesic requirements will be recorded post operatively.

      Anaesthetic management Preoperative management

      All patients will be visited before surgery to be clinically assessed and the preoperative
      surveillance includes:

        -  Haematological screening (Complete blood picture, Serum electrolytes).

        -  Standard coagulation studies e.g. prothrombin time, international normalized ratio
           (PT-INR).

      On arrival to the operating room and before anaesthetic induction all patients will be
      monitored by the standard routine monitoring, which include:

        -  A 5-lead electrocardiography.

        -  A non-invasive blood pressure (NIBP) (mmHg).

        -  Pulse oximetry (%).

        -  Capnography. (End Tidal CO2 pattern and value in mmHg).

        -  Temperature monitoring. A peripheral intravenous cannula of 20 gauges will be inserted
           in a dorsal vein of the non-dominant hand.

      Premedication with Midazolam in a dose of 0.02mg/ Kg will be used. Induction Preoxygenation
      with 100 % O2 for 3 minutes. General anaesthesia will be induced by propofol (2 mg/kg) and
      atracurium (0.5 mg/kg) intravenously guided by a nerve stimulator, followed by endotracheal
      intubation after loss of train of four.

      All the patients will receive i.v. acetaminophen (1000 mg) _20 min after induction and i.v.
      ketorolac (30 mg).

      Local analgesia will be injected by surgeon. All patients will receive beta blocker (Inderal
      1mg) and magnesium sulphate (15-30mg/kg) for achieving hypotensive anaesthesia.

      Maintenance Maintenance of general anaesthesia with a mixture of isoflurane (1MAC) and
      oxygen.

      All patients will be mechanically ventilated with an anaesthesia machine to keep SpO2 > 95%
      and end-tidal CO2 between 35-45 mmHg.

      Additional atracurium will be administrated as appropriate in bolus doses if needed.

      Group A Fentanyl (1mg/kg i.v.) will be administered before general anaesthesia (GA). GA will
      be maintained with inhalation anaesthetics (isoflurane) at a minimum alveolar concentration
      of 0.7-1.3.

      Group B Opioid free anesthesia (syringe of saline is given instead of fentanyl) and the same
      general anesthesia is given as group A(muscle relaxant ,propofol, inhalation for maintance).

      Recovery At the end of surgery, isoflurane will be discontinued, 100% oxygen will be given,
      all patients will be planned for extubation in the operating room depending on recovery
      criteria after complete reversal of muscle relaxant with neostigmine (up to 5 mg).

      Tracheal extubation will be performed in a semi- sitting position after fulfilling the
      criteria for extubation. Extubation criteria include: a fully conscious patient, haemodynamic
      stability, reversal of neuromuscular blockade, TOF ratio 0.9 - 1 on nerve stimulator, and the
      ability of head lift for 5 seconds.

      Postoperative multimodal pain management Postoperative pain will be treated with i.v.
      acetaminophen (1000mg) and i.v. ketorolac (30 mg) every 6 h for the first 24 h. Postoperative
      pain will be measured on an 11-point numeric pointscale (NPS).

      management of PONV Dexamethasone (8 mg i.v.) will be administered during induction,
      ondansetron (4 mg i.v.) and metoclopramide (10 mg i.v.) post operative if Patients
      complaining of PONV after discharge from the PACU.

      Measurements

        1. Demographic data:

           Age (years), sex, weight (kilograms).

        2. Hemodynamic parameters:

             -  Pulse oximetry (%)

             -  Heart rate (HR). Beats/minute

             -  Mean Non-Invasive arterial blood pressure (NIBP) (mmHg)

        3. Pain assessment The level of pain will be assessed on an 11-point NPS. Patients will be
           asked to determine their own 'acceptable' pain score.

           The 11-point numeric scale ranges from '0' representing no pain extreme to '10'
           representing the other pain extreme (worst pain imaginable).(8)

        4. Nausea and vomiting assessment (table2,3) Patients will be asked to rate the worst
           episode of PONV on a four-point verbal rating scale (VRS) (none, mild, moderate, or
           severe). Patients were also will be asked whether they experienced retching or vomiting.

        5. Sedation assessment

      Sedation score:

      0. Alert

        1. Mild, drowsy, easy to awake

        2. Moderate, easy to arouse

        3. Severe: somnolent difficult to arouse

        4. Sleeping The Sedation score will be documented at 0, 1, 2, 4, 6, 12, 18, and 24 hours.

      6. Satsifacation of patient assessment by QoR40 questionnaire The QoR-40 is a global measure
      of quality of recovery. It incorporates five dimensions: patient support, comfort, emotions,
      physical independence, and pain; each item is graded on a five-point Likert scale. QoR-40
      scores range from 40 (extremely poor quality of recovery) to 200 (excellent quality of
      recovery).(29) Timing Hemodynamic (blood pressure, pulse) of Patients will be assessed during
      the surgery every 10 minutes and at 1 and 2 h after the end of surgery and at discharge from
      the day unit. At each of these times, the nurse recorded the incidence and worst severity of
      pain, nausea and emesis since the last evaluation using the same criteria as before. Any
      medication will be given for pain or nausea (administered for moderate-severe symptoms, or at
      patient request) will be also recorded, till the time of discharge. Patients will be
      discharged with medication comprising slow-release ibuprofen. The following day, the
      researcher will telephone the patient to assess the incidence and worst severity of pain,
      nausea and emesis since discharge and whether any analgesia or antiemetics will be taken.
      Patients will be also asked to record their satisfaction with the control of pain, the
      control of sickness and their overall day surgery experience on 11-point (0-10) verbal rating
      scales.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: To compare between opioid and opioid free anaesthesia on post-operative nausea and vomiting in middle ear surgery
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
masking description: Doctors, patients and outcomes assessors will be blinded regarding the technique used in anesthesia.
measure: PONV
time frame: 72 hours
description: Post operative nausea and vomiting from 0-3 for nausea and 0 to 4 for vomiting
measure: analgesia.post-operative pain
time frame: 72 hours
description: analgesia, post-operative VAS score
measure: Patient satisfaction
time frame: 72 hours
description: satisfaction degree by QoR40 questionnaire from 40 to 200
measure: Drowsiness
time frame: 72 hours
description: Drowsiness scores by RAMSY sedation score from 0 to 4
arm group label: Fentanyl Opioid Anesthesia
arm group type: Active Comparator
description: Fentanyl (1mg/kg i.v.) will be administered before general anaesthesia (GA). GA will be maintained with inhalation anaesthetics (isoflurane) at a minimum alveolar concentration of 0.7-1.3.
arm group label: Saline Nonopioid Anesthesia
arm group type: Placebo Comparator
description: Opioid free anesthesia (syringe of saline is given instead of fentanyl) and the same general anesthesia is given as group A(muscle relaxant ,propofol, inhalation for maintance).
intervention type: Drug
intervention name: Fentanyl Opioid anesthesia
description: To compare between opioid and opioid free anaesthesia on post-operative nausea and vomiting in middle ear surgery
arm group label: Fentanyl Opioid Anesthesia
intervention type: Drug
intervention name: Saline Nonopioid anesthesia
description: To compare between opioid and opioid free anaesthesia on post-operative nausea and vomiting in middle ear surgery
arm group label: Saline Nonopioid Anesthesia
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
facility: 
country: Egypt
citation: Quemby DJ. Day surgery development and practice: key factors for a successful pathway. CEACCP 2014;14: 256-61.
citation: Moore KL, Dalley AF. Clinically orientated anatomy. 4th ed. Philadelphia: Lippinocott Williams & Wilkins; 1999.
citation: Dhillon RS, East CA. Ear, nose, throat, and head and neck surgery: an illustrated colored text. 2nd ed. New York, Edinburgh: Churchill Livingstone;1999
citation: Deacock AR. Aspects of anaesthesia for middle ear surgery an blood loss during stapedectomy. Proc R Soc Med. 1971 Dec;64(12):1226-8. No abstract available.
PMID: 4399792
citation: Miller RD. Miller's anesthesia, 6th ed. Vol 2. New York: Elsevier/Churchill Livingstone; 2005.
citation: Morgan EG, Mikhail MS, Murray MJ. Clinical anesthesiology. 4th ed. New York: Lange Medical Books/McGraw-Hill; 2006.
citation: Bailey CR. Management of outpatient ear, nose and throat surgery. Curr Opin Anaesthesiol. 2001 Dec;14(6):617-21. doi: 10.1097/00001503-200112000-00003.
PMID: 17019154
citation: Honkavaara P, Saarnivaara L, Klemola UM. Prevention of nausea and vomiting with transdermal hyoscine in adults after middle ear surgery during general anaesthesia. Br J Anaesth. 1994 Dec;73(6):763-6. doi: 10.1093/bja/73.6.763.
PMID: 7880660
citation: Fujii Y, Toyooka H, Tanaka H. Prophylactic antiemetic therapy with a combination of granisetron and dexamethasone in patients undergoing middle ear surgery. Br J Anaesth. 1998 Nov;81(5):754-6. doi: 10.1093/bja/81.5.754.
PMID: 10193289
citation: Fujii Y, Saitoh Y, Tanaka H, Toyooka H. Anti-emetic efficacy of prophylactic granisetron compared with perphenazine for the prevention of post-operative vomiting in children. Eur J Anaesthesiol. 1999 May;16(5):304-7. doi: 10.1046/j.1365-2346.1999.00483.x.
PMID: 10390665
citation: Gombar S, Kaur J, Kumar Gombar K, Dass A, Singh A. Superior anti-emetic efficacy of granisetron-dexamethasone combination in children undergoing middle ear surgery. Acta Anaesthesiol Scand. 2007 May;51(5):621-4. doi: 10.1111/j.1399-6576.2007.01296.x.
PMID: 17430326
citation: Bovill JG, Sebel PS, Stanley TH. Opioid analgesics in anesthesia: with special reference to their use in cardiovascular anesthesia. Anesthesiology. 1984 Dec;61(6):731-55.
PMID: 6150663
citation: Long DR, Lihn AL, Friedrich S, Scheffenbichler FT, Safavi KC, Burns SM, Schneider JC, Grabitz SD, Houle TT, Eikermann M. Association between intraoperative opioid administration and 30-day readmission: a pre-specified analysis of registry data from a healthcare network in New England. Br J Anaesth. 2018 May;120(5):1090-1102. doi: 10.1016/j.bja.2017.12.044. Epub 2018 Mar 9.
PMID: 29661386
citation: Golembiewski J, Chernin E, Chopra T. Prevention and treatment of postoperative nausea and vomiting. Am J Health Syst Pharm. 2005 Jun 15;62(12):1247-60; quiz 1261-2. doi: 10.1093/ajhp/62.12.1247.
PMID: 15947124
citation: Macario A, Weinger M, Truong P, Lee M. Which clinical anesthesia outcomes are both common and important to avoid? The perspective of a panel of expert anesthesiologists. Anesth Analg. 1999 May;88(5):1085-91. doi: 10.1097/00000539-199905000-00023.
PMID: 10320175
citation: Smith I, Terhoeve PA, Hennart D, Feiss P, Harmer M, Pourriat JL, Johnson IA. A multicentre comparison of the costs of anaesthesia with sevoflurane or propofol. Br J Anaesth. 1999 Oct;83(4):564-70. doi: 10.1093/bja/83.4.564.
PMID: 10673870
citation: Smith I, Thwaites AJ. Target-controlled propofol vs. sevoflurane: a double-blind, randomised comparison in day-case anaesthesia. Anaesthesia. 1999 Aug;54(8):745-52. doi: 10.1046/j.1365-2044.1999.00953.x.
PMID: 10460526
citation: Fleischmann E, Akca O, Wallner T, Arkilic CF, Kurz A, Hickle RS, Zimpfer M, Sessler DI. Onset time, recovery duration, and drug cost with four different methods of inducing general anesthesia. Anesth Analg. 1999 Apr;88(4):930-5. doi: 10.1097/00000539-199904000-00046.
PMID: 10195551
citation: Fredman B, Nathanson MH, Smith I, Wang J, Klein K, White PF. Sevoflurane for outpatient anesthesia: a comparison with propofol. Anesth Analg. 1995 Oct;81(4):823-8. doi: 10.1097/00000539-199510000-00028.
PMID: 7574017
citation: Shakir AAK, Ramachandra V, Hasan MA. Day surgery postoperative nausea and vomiting at home related to preoperative fentanyl. J One-day Surg 1997;6:10-1.
citation: Apfel CC, Laara E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology. 1999 Sep;91(3):693-700. doi: 10.1097/00000542-199909000-00022.
PMID: 10485781
citation: Vandermeulen EP. Controlling the stress response. In: White PF (ed). Textbook of Intravenous Anesthesia. Baltimore: Williams & Wilkins; 1997. p. 565-79.
citation: Borgeat A, Wilder-Smith OH, Saiah M, Rifat K. Subhypnotic doses of propofol possess direct antiemetic properties. Anesth Analg. 1992 Apr;74(4):539-41. doi: 10.1213/00000539-199204000-00013.
PMID: 1554120
citation: Gan TJ, Glass PSA. Balanced anesthesia. In: White PF (ed). Textbook of Intravenous Anesthesia. Baltimore: Williams & Wilkins; 1997. p. 347-74.
citation: Smith I. Inhalational anesthetic agents. In: Hemmings HC, Hopkins PM (eds). Foundations of Anesthesia. 2nd ed. London: Elsevier; 2005. p. 311-21.
citation: 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.
PMID: 24554545
citation: Bakan M, Umutoglu T, Topuz U, Uysal H, Bayram M, Kadioglu H, Salihoglu Z. Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double-blinded study. Braz J Anesthesiol. 2015 May-Jun;65(3):191-9. doi: 10.1016/j.bjane.2014.05.001. Epub 2014 Jun 3.
PMID: 25925031
citation: Feld JM, Hoffman WE, Stechert MM, Hoffman IW, Ananda RC. Fentanyl or dexmedetomidine combined with desflurane for bariatric surgery. J Clin Anesth. 2006 Feb;18(1):24-8. doi: 10.1016/j.jclinane.2005.05.009.
PMID: 16517328
citation: Gornall BF, Myles PS, Smith CL, Burke JA, Leslie K, Pereira MJ, Bost JE, Kluivers KB, Nilsson UG, Tanaka Y, Forbes A. Measurement of quality of recovery using the QoR-40: a quantitative systematic review. Br J Anaesth. 2013 Aug;111(2):161-9. doi: 10.1093/bja/aet014. Epub 2013 Mar 6.
PMID: 23471753
responsible party type: Principal Investigator
investigator affiliation: University of Alexandria
investigator full name: Mohammad Hazem I. Ahmad Sabry
investigator title: Lecturer of Anesthesia
mesh term: Fentanyl
mesh term: Anesthetics
sharing ipd: No