xml: <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/NCT06026527</url>
    </required_header>
    <id_info>
      <org_study_id>MagSulf1234</org_study_id>
      <nct_id>NCT06026527</nct_id>
    </id_info>
    <brief_title>Intra-operative Magnesium Sulphate for Post-operative Pain in Patients Undergoing Total Abdominal Hysterectomy Under General Anesthesia</brief_title>
    <official_title>Intra-operative Magnesium Sulphate for Post-operative Pain in Patients Undergoing Total Abdominal Hysterectomy Under General Anesthesia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tribhuvan University Teaching Hospital, Institute Of Medicine.</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Tribhuvan University Teaching Hospital, Institute Of Medicine.</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Post-operative pain management is a complex entity. It is one of the most critical parameters&#xD;
        in the enhanced recovery after surgery protocol. Adequate postoperative pain relief leads to&#xD;
        earlier mobilisation, shortened hospital stay, reduced hospital costs and increased patient&#xD;
        satisfaction.&#xD;
  &#xD;
        For post-operative analgesia, opioids have long been the mainstay of drugs used; however,&#xD;
        they produce unwanted side effects, such as respiratory depression, nausea, vomiting and&#xD;
        dependence. The major goal in postoperative pain management is to minimise the dose of a&#xD;
        single medication and lessen its side effects, while still providing adequate analgesia by&#xD;
        the use of multimodal analgesia. Paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs),&#xD;
        regional techniques like epidural analgesia, different kind of blocks and local wound&#xD;
        infiltration are some of the components of multimodal approach to post- operative analgesia.&#xD;
  &#xD;
        Besides, there are some drugs that may be used as adjuvants to opioids to enhance the&#xD;
        analgesic efficacy and facilitate opioid sparing with a reduction in opioid related side&#xD;
        effects. Magnesium sulphate, due to its N- Methyl D- Aspartate (NMDA) blocking property, has&#xD;
        been studied as one of such non opioid adjuvants. The outcome of many of these studies is in&#xD;
        favour of magnesium sulphate but there are negative reports as well.&#xD;
  &#xD;
        So, in this study the investigators aim to evaluate the efficacy of intra-operative&#xD;
        intravenous magnesium sulphate for post-operative pain and opioid use in patients undergoing&#xD;
        abdominal hysterectomy under general anaesthesia.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        All women who have been planned for total abdominal hysterectomy will be enrolled in the&#xD;
        study. Patients who do not meet the inclusion criteria or those who refuse to participate&#xD;
        will be excluded from study . Other enrolled patients who meet the eligibility criteria will&#xD;
        be randomised and allocated to two study groups- Magnesium (M) group and Control (C) group by&#xD;
        computer generated numbers that will be concealed in a sequentially numbered, opaque sealed&#xD;
        envelopes. The envelopes will be opened before the surgery begins by a doctor not involved in&#xD;
        the study and not assigned to the Gynaecology operating room. The drug will be prepared and&#xD;
        labelled study drug as: In group M- Magnesium sulphate @ 50mg/ kg in 100 ml of normal saline&#xD;
        and in group C- 100 ml of normal saline. Anaesthetic management, administration of the study&#xD;
        drug and any intra-operative changes in vitals requiring treatment will be recorded in the&#xD;
        anaesthesia management sheet by another doctor who is assigned to Gynaecology operating room.&#xD;
  &#xD;
        A day prior to surgery, eligible patients will be explained in detail about the purpose of&#xD;
        study, need, benefits and risks of procedure. The participants will be explained about&#xD;
        numerical rating scale (NRS) of pain, how to use it and rate it during post-operative period.&#xD;
        Written informed consent will be obtained. The patients will be counselled about fasting&#xD;
        protocol and asked to remain nil per oral of 2 hours for clear liquid, 6 hours for light&#xD;
        foods and 8 hours for fatty food.&#xD;
  &#xD;
        In pre-operative holding area : Baseline vitals systolic blood pressure (SBP), diastolic&#xD;
        blood pressure (DBP), mean arterial blood pressure (MAP), heart rate (HR), respiratory rate&#xD;
        (RR), Oxygen saturation (SpO2) will be recorded. Intravenous access will be established with&#xD;
        an 18 or 20 gauge cannula. A 3-way stopcock will be attached to the cannula and Lactated&#xD;
        Ringer's will be infused @ 100ml/hr.&#xD;
  &#xD;
        In the operating room: Standard American Society of Anaesthesiologists monitors will be&#xD;
        attached. All patients will be subjected to a standardised anaesthetic protocol. Induction of&#xD;
        general anaesthesia, intubation, ventilation parameter set up and maintenance of anaesthesia&#xD;
        will be done as per standard anaesthetic practice in our institute.&#xD;
  &#xD;
        Meanwhile, at the time of induction, 100 ml of study drug will be infused via side port of&#xD;
        3-way stopcock over 20-30 minutes. Ringer lactate solution will be infused throughout the&#xD;
        surgery as per standard practice in our institute. Hemodynamic parameters SBP, DBP, HR, SpO2,&#xD;
        RR will be monitored and recorded as per anaesthesia protocol. Additional analgesia during&#xD;
        the peri-operative period will be standardised with IV Paracetamol 15 mg/kg post induction&#xD;
        and IV Fentanyl 0.5 mcg/kg every hour of intra-operative period and any additional dosing of&#xD;
        analgesia will be recorded. Urine output monitoring will be done on hourly basis. If less&#xD;
        than 0.5 ml/kg/hr, underlying cause will be looked for, and if no other causes is found, Mg&#xD;
        toxicity will be suspected and serum magnesium level will be sent. Meanwhile necessary&#xD;
        medical management will be done. Post operative nausea and vomiting (PONV) prophylaxis will&#xD;
        be standardised in both groups of patient. IV Ondansetron 4mg single dose 15 to 20 minutes&#xD;
        before extubation will be given. 0.25% Bupivacaine not exceeding 2 mg/kg dose will be&#xD;
        administered locally at the site of surgical incision at the end of surgery. Reversal of&#xD;
        muscle relaxation and extubation will be done as per attending anaesthesiologist. Patient&#xD;
        will be transferred to recovery room.&#xD;
  &#xD;
        Post operatively: Patients will be held in recovery room until adequate recovery from&#xD;
        anaesthesia as judged by the Modified Aldrete Score. Score ≥ 9 will be deemed adequate. Post&#xD;
        operative pain assessment will be done with Numerical Rating Scale (NRS). The NRS is a pain&#xD;
        screening tool, commonly used to assess pain severity at that moment in time using a 0-10&#xD;
        scale, with zero meaning &quot;no pain&quot; and 10 meaning &quot;the worst pain imaginable&quot;. Pain&#xD;
        assessment will be done by the attending nurse at time 0, 1, 6, 12, 18, 24 hours. The time 0&#xD;
        will be the first assessment of pain done in the recovery room once the patient is fully&#xD;
        awake. If NRS &gt; 3 at any time within 24 hours, IV Tramadol 50 mg will be given as rescue&#xD;
        analgesia. NRS and vitals at this point will be recorded. If NRS &gt; 3 even after 10 minutes of&#xD;
        rescue analgesic , second dose of 50 mg of IV Tramadol up to a total dose of 150 mg including&#xD;
        the initial bolus will be given.Vitals SBP, DBP, MAP, HR, RR, SpO2 will be monitored and&#xD;
        recorded at 0, 1, 6, 12, 18, 24 hours. 24 hours total opioid consumption post-operatively&#xD;
        will be recorded. Side effects of magnesium sulphate including nausea/ vomiting, flushing,&#xD;
        hypotension, bradycardia, blurring of vision, decreased respiratory rate , muscle weakness,&#xD;
        loss of deep tendon reflexes will be recorded and managed as per protocol.&#xD;
  &#xD;
        Maintenance analgesia will be standardised as : IV Paracetamol 15 mg/kg every 6 hours and IV&#xD;
        Ketorolac 30mg every 8 hours. For postoperative nausea and vomiting, IV Ondansetron 4 mg will&#xD;
        be given every 8 hours as standard practice.&#xD;
  &#xD;
        Management of the patients for any side effects will be done as described below:&#xD;
  &#xD;
        Hypotension with SBP &lt; 90 mmHg will be managed with IV Mephentermine 6mg bolus and repeated&#xD;
        as required.&#xD;
  &#xD;
        Bradycardia with HR &lt; 50 beats/min will be managed with IV Atropine 0.6 mg bolus.&#xD;
  &#xD;
        Respiratory depression will be graded as mild (RR 10-12), moderate (RR 8-10) and severe ( RR&#xD;
        &lt;8). Oxygen @ 6 L/ minute will supplemented via face mask. In case of severe respiratory&#xD;
        depression, serum magnesium level will be sent in suspicion magnesium toxicity. If magnesium&#xD;
        level comes out to be normal, respiratory depression due to opioid will be suspected and IV&#xD;
        naloxone 0.4 mg will be given and repeated 2-3 minutes until RR rises above 8. Total naloxone&#xD;
        dose will not exceed 10 mg.&#xD;
  &#xD;
        Sedation will be quantified according to Pasero Opioid-induced Sedation Scale ( POSS) . In&#xD;
        case of POSS &gt;3, IV Naloxone will be infused as mentioned earlier.&#xD;
  &#xD;
        If milder signs of hypermagnesemia like nausea, dizziness, confusion is noticed, it will be&#xD;
        recorded and informed to the principal investigator. Meanwhile serum Magnesium level will be&#xD;
        sent. The principal investigator will then attend the patient for signs of moderate&#xD;
        hypermagnesemia and manage accordingly. Patients with normal renal function clinically&#xD;
        assessed as urine output &gt;0.5ml/kg/hour and mild hypermagnesemia will require no treatment.&#xD;
        If signs of moderate hypermagnesemia occur, the principal investigator will attend the case&#xD;
        for close monitoring of the ECG, blood pressure, neuromuscular function and respiratory&#xD;
        function. If either hyporeflexia assessed as loss of patellar reflex, respiratory depression&#xD;
        or changes in ECG is noticed individually or all at once, IV normal saline at 150 ml/hour and&#xD;
        IV calcium gluconate 1 gm over 5 minutes will be infused. The rationale is that the actions&#xD;
        of magnesium in neuromuscular and cardiac function become antagonized by calcium. In absence&#xD;
        of improvement, same dose will be repeated. In case of severe hypermagnesemia, intravenous&#xD;
        loop diuretic, IV Furosemide 1 mg/kg will be given to increase renal magnesium excretion.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">January 2024</completion_date>
    <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
    <phase>Phase 3</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>To evaluate the efficacy of magnesium sulphate for post-operative pain</measure>
      <time_frame>At 0, 1, 6,12 18 and 24 hours post-operatively</time_frame>
      <description>Post operative pain will be assessed by using Numerical rating score (NRS) of pain. The NRS is a 0-10 scale, with zero meaning &quot;no pain&quot; and 10 meaning &quot;the worst pain imaginable&quot;</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Comparison of Numerical Rating Scale (NRS) score of pain</measure>
      <time_frame>at 0, 1, 6, 12, 18, 24 hours post-operatively</time_frame>
      <description>Comparison of Numerical Rating Scale score between Magnesium and control group.The NRS is a 0-10 scale, with zero meaning &quot;no pain&quot; and 10 meaning &quot;the worst pain imaginable&quot;</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Opioid as rescue analgesic use</measure>
      <time_frame>The time to first rescue analgesic use within 24 hours post-operatively will be noted</time_frame>
      <description>To compare the timing of first rescue analgesic used</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total opioid use</measure>
      <time_frame>within 24 hours post-operatively</time_frame>
      <description>Comparison of total opioid used between two groups</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Side effects</measure>
      <time_frame>within 24 hours post-operatively</time_frame>
      <description>To determine any side effects of magnesium sulphate</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">42</enrollment>
    <condition>Post-operative Pain</condition>
    <arm_group>
      <arm_group_label>Group M</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Magnesium group</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Group C</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Control group</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Magnesium sulfate</intervention_name>
      <description>50 mg/kg Magnesium sulphate in 93-95 ml Normal Saline ( making a total of 100 ml solution )will be infused intravenously over 20-30 minutes in the participants allocated to M group starting from the moment of induction of anaesthesia</description>
      <arm_group_label>Group M</arm_group_label>
      <other_name>Magnesium sulphate</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Normal Saline</intervention_name>
      <description>100 ml Normal Saline will be infused intravenously over 20-30 minutes in the participants allocated to control group starting from the moment of induction of anaesthesia</description>
      <arm_group_label>Group C</arm_group_label>
      <other_name>NS</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patient undergoing elective abdominal hysterectomy.&#xD;
  &#xD;
            -  Between the ages of 18- 65.&#xD;
  &#xD;
            -  American Society of Anesthesiologists Physical Status (ASA PS) I and II.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Neurological and psychiatric disorder.&#xD;
  &#xD;
            -  Drug or alcohol abuse.&#xD;
  &#xD;
            -  Patients with a known or suspected allergy to magnesium sulphate.&#xD;
  &#xD;
            -  Patients with any contraindication to magnesium sulphate (heart blocks, neuromuscular&#xD;
               diseases)&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <gender_based>Yes</gender_based>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Subhash P Acharya, MD FACC FCCP</last_name>
      <role>Study Chair</role>
      <affiliation>Tribhuvan University Teaching Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Bashu D Parajuli, MD, FOA</last_name>
      <role>Study Chair</role>
      <affiliation>Tribhuvan University Teaching Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Pankaj Joshi, MD, FLTA (ICA)</last_name>
      <role>Study Chair</role>
      <affiliation>Tribhuvan University Teaching Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Priyanka Dahal, MD Resident</last_name>
      <role>Principal Investigator</role>
      <affiliation>Tribhuvan University Teaching Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Priyanka Dahal, MD Resident</last_name>
      <phone>+9779863930790</phone>
      <email>priyankadahal11@gmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Bashu D Parajuli, MD, FOA</last_name>
      <phone>+9779851179038</phone>
      <email>bashuparajuli2012@gmail.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Tribhuvan University Teaching Hospital</name>
        <address>
          <city>Kathmandu</city>
          <state>Bagmati</state>
          <zip>44600</zip>
          <country>Nepal</country>
        </address>
      </facility>
      <contact>
        <last_name>Priyanka Dahal, MD Resident Anaesthesiology</last_name>
        <phone>+977 9863930790</phone>
        <email>priyankadahal11@gmail.com</email>
      </contact>
      <contact_backup>
        <last_name>Bashu D Parajuli, MD</last_name>
        <phone>+977 9851179038</phone>
        <email>bashuparajuli2012@gmail.com</email>
      </contact_backup>
      <investigator>
        <last_name>Priyanka Dahal, MBBS</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Nepal</country>
    </location_countries>
    <reference>
      <citation>Shekhar C, Paswan B, Singh A. Prevalence, sociodemographic determinants and self-reported reasons for hysterectomy in India. Reprod Health. 2019 Aug 2;16(1):118. doi: 10.1186/s12978-019-0780-z.</citation>
      <PMID>31375139</PMID>
    </reference>
    <reference>
      <citation>Clarke-Pearson DL, Geller EJ. Complications of hysterectomy. Obstet Gynecol. 2013 Mar;121(3):654-673. doi: 10.1097/AOG.0b013e3182841594.</citation>
      <PMID>23635631</PMID>
    </reference>
    <reference>
      <citation>Perniola A, Gupta A, Crafoord K, Darvish B, Magnuson A, Axelsson K. Intraabdominal local anaesthetics for postoperative pain relief following abdominal hysterectomy: a randomized, double-blind, dose-finding study. Eur J Anaesthesiol. 2009 May;26(5):421-9. doi: 10.1097/EJA.0b013e3283261b53.</citation>
      <PMID>19521298</PMID>
    </reference>
    <reference>
      <citation>Chung F, Ritchie E, Su J. Postoperative pain in ambulatory surgery. Anesth Analg. 1997 Oct;85(4):808-16. doi: 10.1097/00000539-199710000-00017. Erratum In: Anesth Analg 1997 Nov;85(5):986.</citation>
      <PMID>9322460</PMID>
    </reference>
    <reference>
      <citation>Kehlet H, Dahl JB. The value of &quot;multimodal&quot; or &quot;balanced analgesia&quot; in postoperative pain treatment. Anesth Analg. 1993 Nov;77(5):1048-56. doi: 10.1213/00000539-199311000-00030. No abstract available.</citation>
      <PMID>8105724</PMID>
    </reference>
    <reference>
      <citation>White PF. The role of non-opioid analgesic techniques in the management of pain after ambulatory surgery. Anesth Analg. 2002 Mar;94(3):577-85. doi: 10.1097/00000539-200203000-00019. No abstract available.</citation>
      <PMID>11867379</PMID>
    </reference>
    <reference>
      <citation>Woolf CJ, Thompson SWN. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain. 1991 Mar;44(3):293-299. doi: 10.1016/0304-3959(91)90100-C.</citation>
      <PMID>1828878</PMID>
    </reference>
    <reference>
      <citation>Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009 Sep;10(9):895-926. doi: 10.1016/j.jpain.2009.06.012.</citation>
      <PMID>19712899</PMID>
    </reference>
    <reference>
      <citation>Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000 Jun 9;288(5472):1765-9. doi: 10.1126/science.288.5472.1765.</citation>
      <PMID>10846153</PMID>
    </reference>
    <reference>
      <citation>Tramer MR, Schneider J, Marti RA, Rifat K. Role of magnesium sulfate in postoperative analgesia. Anesthesiology. 1996 Feb;84(2):340-7. doi: 10.1097/00000542-199602000-00011.</citation>
      <PMID>8602664</PMID>
    </reference>
    <reference>
      <citation>Wilder-Smith CH, Knopfli R, Wilder-Smith OH. Perioperative magnesium infusion and postoperative pain. Acta Anaesthesiol Scand. 1997 Sep;41(8):1023-7. doi: 10.1111/j.1399-6576.1997.tb04830.x.</citation>
      <PMID>9311401</PMID>
    </reference>
    <reference>
      <citation>Ko SH, Lim HR, Kim DC, Han YJ, Choe H, Song HS. Magnesium sulfate does not reduce postoperative analgesic requirements. Anesthesiology. 2001 Sep;95(3):640-6. doi: 10.1097/00000542-200109000-00016.</citation>
      <PMID>11575536</PMID>
    </reference>
    <reference>
      <citation>Kara H, Sahin N, Ulusan V, Aydogdu T. Magnesium infusion reduces perioperative pain. Eur J Anaesthesiol. 2002 Jan;19(1):52-6. doi: 10.1017/s026502150200008x.</citation>
      <PMID>11913804</PMID>
    </reference>
    <reference>
      <citation>Feld JM, Laurito CE, Beckerman M, Vincent J, Hoffman WE. Non-opioid analgesia improves pain relief and decreases sedation after gastric bypass surgery. Can J Anaesth. 2003 Apr;50(4):336-41. doi: 10.1007/BF03021029. English, French.</citation>
      <PMID>12670809</PMID>
    </reference>
    <reference>
      <citation>Taheri A, Haryalchi K, Mansour Ghanaie M, Habibi Arejan N. Effect of low-dose (single-dose) magnesium sulfate on postoperative analgesia in hysterectomy patients receiving balanced general anesthesia. Anesthesiol Res Pract. 2015;2015:306145. doi: 10.1155/2015/306145. Epub 2015 Feb 1.</citation>
      <PMID>25705223</PMID>
    </reference>
    <reference>
      <citation>Breivik H, Borchgrevink PC, Allen SM, Rosseland LA, Romundstad L, Hals EK, Kvarstein G, Stubhaug A. Assessment of pain. Br J Anaesth. 2008 Jul;101(1):17-24. doi: 10.1093/bja/aen103. Epub 2008 May 16.</citation>
      <PMID>18487245</PMID>
    </reference>
    <reference>
      <citation>Hammond DA, Stojakovic J, Kathe N, Tran J, Clem OA, Erbach K, King J. Effectiveness and Safety of Magnesium Replacement in Critically Ill Patients Admitted to the Medical Intensive Care Unit in an Academic Medical Center: A Retrospective, Cohort Study. J Intensive Care Med. 2019 Nov-Dec;34(11-12):967-972. doi: 10.1177/0885066617720631. Epub 2017 Jul 13.</citation>
      <PMID>28703019</PMID>
    </reference>
    <reference>
      <citation>Yamaguchi H, Shimada H, Yoshita K, Tsubata Y, Ikarashi K, Morioka T, Saito N, Sakai S, Narita I. Severe hypermagnesemia induced by magnesium oxide ingestion: a case series. CEN Case Rep. 2019 Feb;8(1):31-37. doi: 10.1007/s13730-018-0359-5. Epub 2018 Aug 22.</citation>
      <PMID>30136128</PMID>
    </reference>
    <reference>
      <citation>Kobelt P, Burke K, Renker P. Evaluation of a standardized sedation assessment for opioid administration in the post anesthesia care unit. Pain Manag Nurs. 2014 Sep;15(3):672-81. doi: 10.1016/j.pmn.2013.11.002. Epub 2014 Jan 22.</citation>
      <PMID>24461253</PMID>
    </reference>
    <reference>
      <citation>BELLVILLE JW, BROSS ID, HOWLAND WS. A method for the clinical evaluation of antiemetic agents. Anesthesiology. 1959 Nov-Dec;20:753-60. doi: 10.1097/00000542-195911000-00002. No abstract available.</citation>
      <PMID>13798617</PMID>
    </reference>
    <reference>
      <citation>Blaine J, Chonchol M, Levi M. Renal control of calcium, phosphate, and magnesium homeostasis. Clin J Am Soc Nephrol. 2015 Jul 7;10(7):1257-72. doi: 10.2215/CJN.09750913. Epub 2014 Oct 6. Erratum In: Clin J Am Soc Nephrol. 2015 Oct 7;10(10):1886-7.</citation>
      <PMID>25287933</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 29, 2023</study_first_submitted>
    <study_first_submitted_qc>September 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Tribhuvan University Teaching Hospital, Institute Of Medicine.</investigator_affiliation>
      <investigator_full_name>Priyanka Dahal</investigator_full_name>
      <investigator_title>MD Resident- Anaesthesiology</investigator_title>
    </responsible_party>
    <keyword>Magnesium, Pain, NRS, Abdominal hysterectomy, MgSO4</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pain, Postoperative</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Magnesium Sulfate</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06026527
  org study id: MagSulf1234
  nct id: NCT06026527
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Post-operative pain management is a complex entity. It is one of the most critical parameters
        in the enhanced recovery after surgery protocol. Adequate postoperative pain relief leads to
        earlier mobilisation, shortened hospital stay, reduced hospital costs and increased patient
        satisfaction.
  
        For post-operative analgesia, opioids have long been the mainstay of drugs used; however,
        they produce unwanted side effects, such as respiratory depression, nausea, vomiting and
        dependence. The major goal in postoperative pain management is to minimise the dose of a
        single medication and lessen its side effects, while still providing adequate analgesia by
        the use of multimodal analgesia. Paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs),
        regional techniques like epidural analgesia, different kind of blocks and local wound
        infiltration are some of the components of multimodal approach to post- operative analgesia.
  
        Besides, there are some drugs that may be used as adjuvants to opioids to enhance the
        analgesic efficacy and facilitate opioid sparing with a reduction in opioid related side
        effects. Magnesium sulphate, due to its N- Methyl D- Aspartate (NMDA) blocking property, has
        been studied as one of such non opioid adjuvants. The outcome of many of these studies is in
        favour of magnesium sulphate but there are negative reports as well.
  
        So, in this study the investigators aim to evaluate the efficacy of intra-operative
        intravenous magnesium sulphate for post-operative pain and opioid use in patients undergoing
        abdominal hysterectomy under general anaesthesia.
  All women who have been planned for total abdominal hysterectomy will be enrolled in the
        study. Patients who do not meet the inclusion criteria or those who refuse to participate
        will be excluded from study . Other enrolled patients who meet the eligibility criteria will
        be randomised and allocated to two study groups- Magnesium (M) group and Control (C) group by
        computer generated numbers that will be concealed in a sequentially numbered, opaque sealed
        envelopes. The envelopes will be opened before the surgery begins by a doctor not involved in
        the study and not assigned to the Gynaecology operating room. The drug will be prepared and
        labelled study drug as: In group M- Magnesium sulphate @ 50mg/ kg in 100 ml of normal saline
        and in group C- 100 ml of normal saline. Anaesthetic management, administration of the study
        drug and any intra-operative changes in vitals requiring treatment will be recorded in the
        anaesthesia management sheet by another doctor who is assigned to Gynaecology operating room.
  
        A day prior to surgery, eligible patients will be explained in detail about the purpose of
        study, need, benefits and risks of procedure. The participants will be explained about
        numerical rating scale (NRS) of pain, how to use it and rate it during post-operative period.
        Written informed consent will be obtained. The patients will be counselled about fasting
        protocol and asked to remain nil per oral of 2 hours for clear liquid, 6 hours for light
        foods and 8 hours for fatty food.
  
        In pre-operative holding area : Baseline vitals systolic blood pressure (SBP), diastolic
        blood pressure (DBP), mean arterial blood pressure (MAP), heart rate (HR), respiratory rate
        (RR), Oxygen saturation (SpO2) will be recorded. Intravenous access will be established with
        an 18 or 20 gauge cannula. A 3-way stopcock will be attached to the cannula and Lactated
        Ringer's will be infused @ 100ml/hr.
  
        In the operating room: Standard American Society of Anaesthesiologists monitors will be
        attached. All patients will be subjected to a standardised anaesthetic protocol. Induction of
        general anaesthesia, intubation, ventilation parameter set up and maintenance of anaesthesia
        will be done as per standard anaesthetic practice in our institute.
  
        Meanwhile, at the time of induction, 100 ml of study drug will be infused via side port of
        3-way stopcock over 20-30 minutes. Ringer lactate solution will be infused throughout the
        surgery as per standard practice in our institute. Hemodynamic parameters SBP, DBP, HR, SpO2,
        RR will be monitored and recorded as per anaesthesia protocol. Additional analgesia during
        the peri-operative period will be standardised with IV Paracetamol 15 mg/kg post induction
        and IV Fentanyl 0.5 mcg/kg every hour of intra-operative period and any additional dosing of
        analgesia will be recorded. Urine output monitoring will be done on hourly basis. If less
        than 0.5 ml/kg/hr, underlying cause will be looked for, and if no other causes is found, Mg
        toxicity will be suspected and serum magnesium level will be sent. Meanwhile necessary
        medical management will be done. Post operative nausea and vomiting (PONV) prophylaxis will
        be standardised in both groups of patient. IV Ondansetron 4mg single dose 15 to 20 minutes
        before extubation will be given. 0.25% Bupivacaine not exceeding 2 mg/kg dose will be
        administered locally at the site of surgical incision at the end of surgery. Reversal of
        muscle relaxation and extubation will be done as per attending anaesthesiologist. Patient
        will be transferred to recovery room.
  
        Post operatively: Patients will be held in recovery room until adequate recovery from
        anaesthesia as judged by the Modified Aldrete Score. Score ≥ 9 will be deemed adequate. Post
        operative pain assessment will be done with Numerical Rating Scale (NRS). The NRS is a pain
        screening tool, commonly used to assess pain severity at that moment in time using a 0-10
        scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable". Pain
        assessment will be done by the attending nurse at time 0, 1, 6, 12, 18, 24 hours. The time 0
        will be the first assessment of pain done in the recovery room once the patient is fully
        awake. If NRS > 3 at any time within 24 hours, IV Tramadol 50 mg will be given as rescue
        analgesia. NRS and vitals at this point will be recorded. If NRS > 3 even after 10 minutes of
        rescue analgesic , second dose of 50 mg of IV Tramadol up to a total dose of 150 mg including
        the initial bolus will be given.Vitals SBP, DBP, MAP, HR, RR, SpO2 will be monitored and
        recorded at 0, 1, 6, 12, 18, 24 hours. 24 hours total opioid consumption post-operatively
        will be recorded. Side effects of magnesium sulphate including nausea/ vomiting, flushing,
        hypotension, bradycardia, blurring of vision, decreased respiratory rate , muscle weakness,
        loss of deep tendon reflexes will be recorded and managed as per protocol.
  
        Maintenance analgesia will be standardised as : IV Paracetamol 15 mg/kg every 6 hours and IV
        Ketorolac 30mg every 8 hours. For postoperative nausea and vomiting, IV Ondansetron 4 mg will
        be given every 8 hours as standard practice.
  
        Management of the patients for any side effects will be done as described below:
  
        Hypotension with SBP < 90 mmHg will be managed with IV Mephentermine 6mg bolus and repeated
        as required.
  
        Bradycardia with HR < 50 beats/min will be managed with IV Atropine 0.6 mg bolus.
  
        Respiratory depression will be graded as mild (RR 10-12), moderate (RR 8-10) and severe ( RR
        <8). Oxygen @ 6 L/ minute will supplemented via face mask. In case of severe respiratory
        depression, serum magnesium level will be sent in suspicion magnesium toxicity. If magnesium
        level comes out to be normal, respiratory depression due to opioid will be suspected and IV
        naloxone 0.4 mg will be given and repeated 2-3 minutes until RR rises above 8. Total naloxone
        dose will not exceed 10 mg.
  
        Sedation will be quantified according to Pasero Opioid-induced Sedation Scale ( POSS) . In
        case of POSS >3, IV Naloxone will be infused as mentioned earlier.
  
        If milder signs of hypermagnesemia like nausea, dizziness, confusion is noticed, it will be
        recorded and informed to the principal investigator. Meanwhile serum Magnesium level will be
        sent. The principal investigator will then attend the patient for signs of moderate
        hypermagnesemia and manage accordingly. Patients with normal renal function clinically
        assessed as urine output >0.5ml/kg/hour and mild hypermagnesemia will require no treatment.
        If signs of moderate hypermagnesemia occur, the principal investigator will attend the case
        for close monitoring of the ECG, blood pressure, neuromuscular function and respiratory
        function. If either hyporeflexia assessed as loss of patellar reflex, respiratory depression
        or changes in ECG is noticed individually or all at once, IV normal saline at 150 ml/hour and
        IV calcium gluconate 1 gm over 5 minutes will be infused. The rationale is that the actions
        of magnesium in neuromuscular and cardiac function become antagonized by calcium. In absence
        of improvement, same dose will be repeated. In case of severe hypermagnesemia, intravenous
        loop diuretic, IV Furosemide 1 mg/kg will be given to increase renal magnesium excretion.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  measure: To evaluate the efficacy of magnesium sulphate for post-operative pain
  time frame: At 0, 1, 6,12 18 and 24 hours post-operatively
  description: Post operative pain will be assessed by using Numerical rating score (NRS) of pain. The NRS is a 0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable"
  measure: Comparison of Numerical Rating Scale (NRS) score of pain
  time frame: at 0, 1, 6, 12, 18, 24 hours post-operatively
  description: Comparison of Numerical Rating Scale score between Magnesium and control group.The NRS is a 0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable"
  measure: Opioid as rescue analgesic use
  time frame: The time to first rescue analgesic use within 24 hours post-operatively will be noted
  description: To compare the timing of first rescue analgesic used
  measure: Total opioid use
  time frame: within 24 hours post-operatively
  description: Comparison of total opioid used between two groups
  measure: Side effects
  time frame: within 24 hours post-operatively
  description: To determine any side effects of magnesium sulphate
  arm group label: Group M
  arm group type: Experimental
  description: Magnesium group
  arm group label: Group C
  arm group type: Placebo Comparator
  description: Control group
  intervention type: Drug
  intervention name: Magnesium sulfate
  description: 50 mg/kg Magnesium sulphate in 93-95 ml Normal Saline ( making a total of 100 ml solution )will be infused intravenously over 20-30 minutes in the participants allocated to M group starting from the moment of induction of anaesthesia
  arm group label: Group M
  other name: Magnesium sulphate
  intervention type: Drug
  intervention name: Normal Saline
  description: 100 ml Normal Saline will be infused intravenously over 20-30 minutes in the participants allocated to control group starting from the moment of induction of anaesthesia
  arm group label: Group C
  other name: NS
  criteria: 
  gender: Female
  gender based: Yes
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Subhash P Acharya, MD FACC FCCP
  role: Study Chair
  affiliation: Tribhuvan University Teaching Hospital
  last name: Bashu D Parajuli, MD, FOA
  role: Study Chair
  affiliation: Tribhuvan University Teaching Hospital
  last name: Pankaj Joshi, MD, FLTA (ICA)
  role: Study Chair
  affiliation: Tribhuvan University Teaching Hospital
  last name: Priyanka Dahal, MD Resident
  role: Principal Investigator
  affiliation: Tribhuvan University Teaching Hospital
  last name: Priyanka Dahal, MD Resident
  phone: +9779863930790
  email: priyankadahal11@gmail.com
  last name: Bashu D Parajuli, MD, FOA
  phone: +9779851179038
  email: bashuparajuli2012@gmail.com
  facility: 
  contact: 
  contact backup: 
  investigator: 
  country: Nepal
  citation: Shekhar C, Paswan B, Singh A. Prevalence, sociodemographic determinants and self-reported reasons for hysterectomy in India. Reprod Health. 2019 Aug 2;16(1):118. doi: 10.1186/s12978-019-0780-z.
  PMID: 31375139
  citation: Clarke-Pearson DL, Geller EJ. Complications of hysterectomy. Obstet Gynecol. 2013 Mar;121(3):654-673. doi: 10.1097/AOG.0b013e3182841594.
  PMID: 23635631
  citation: Perniola A, Gupta A, Crafoord K, Darvish B, Magnuson A, Axelsson K. Intraabdominal local anaesthetics for postoperative pain relief following abdominal hysterectomy: a randomized, double-blind, dose-finding study. Eur J Anaesthesiol. 2009 May;26(5):421-9. doi: 10.1097/EJA.0b013e3283261b53.
  PMID: 19521298
  citation: Chung F, Ritchie E, Su J. Postoperative pain in ambulatory surgery. Anesth Analg. 1997 Oct;85(4):808-16. doi: 10.1097/00000539-199710000-00017. Erratum In: Anesth Analg 1997 Nov;85(5):986.
  PMID: 9322460
  citation: Kehlet H, Dahl JB. The value of "multimodal" or "balanced analgesia" in postoperative pain treatment. Anesth Analg. 1993 Nov;77(5):1048-56. doi: 10.1213/00000539-199311000-00030. No abstract available.
  PMID: 8105724
  citation: White PF. The role of non-opioid analgesic techniques in the management of pain after ambulatory surgery. Anesth Analg. 2002 Mar;94(3):577-85. doi: 10.1097/00000539-200203000-00019. No abstract available.
  PMID: 11867379
  citation: Woolf CJ, Thompson SWN. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain. 1991 Mar;44(3):293-299. doi: 10.1016/0304-3959(91)90100-C.
  PMID: 1828878
  citation: Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009 Sep;10(9):895-926. doi: 10.1016/j.jpain.2009.06.012.
  PMID: 19712899
  citation: Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000 Jun 9;288(5472):1765-9. doi: 10.1126/science.288.5472.1765.
  PMID: 10846153
  citation: Tramer MR, Schneider J, Marti RA, Rifat K. Role of magnesium sulfate in postoperative analgesia. Anesthesiology. 1996 Feb;84(2):340-7. doi: 10.1097/00000542-199602000-00011.
  PMID: 8602664
  citation: Wilder-Smith CH, Knopfli R, Wilder-Smith OH. Perioperative magnesium infusion and postoperative pain. Acta Anaesthesiol Scand. 1997 Sep;41(8):1023-7. doi: 10.1111/j.1399-6576.1997.tb04830.x.
  PMID: 9311401
  citation: Ko SH, Lim HR, Kim DC, Han YJ, Choe H, Song HS. Magnesium sulfate does not reduce postoperative analgesic requirements. Anesthesiology. 2001 Sep;95(3):640-6. doi: 10.1097/00000542-200109000-00016.
  PMID: 11575536
  citation: Kara H, Sahin N, Ulusan V, Aydogdu T. Magnesium infusion reduces perioperative pain. Eur J Anaesthesiol. 2002 Jan;19(1):52-6. doi: 10.1017/s026502150200008x.
  PMID: 11913804
  citation: Feld JM, Laurito CE, Beckerman M, Vincent J, Hoffman WE. Non-opioid analgesia improves pain relief and decreases sedation after gastric bypass surgery. Can J Anaesth. 2003 Apr;50(4):336-41. doi: 10.1007/BF03021029. English, French.
  PMID: 12670809
  citation: Taheri A, Haryalchi K, Mansour Ghanaie M, Habibi Arejan N. Effect of low-dose (single-dose) magnesium sulfate on postoperative analgesia in hysterectomy patients receiving balanced general anesthesia. Anesthesiol Res Pract. 2015;2015:306145. doi: 10.1155/2015/306145. Epub 2015 Feb 1.
  PMID: 25705223
  citation: Breivik H, Borchgrevink PC, Allen SM, Rosseland LA, Romundstad L, Hals EK, Kvarstein G, Stubhaug A. Assessment of pain. Br J Anaesth. 2008 Jul;101(1):17-24. doi: 10.1093/bja/aen103. Epub 2008 May 16.
  PMID: 18487245
  citation: Hammond DA, Stojakovic J, Kathe N, Tran J, Clem OA, Erbach K, King J. Effectiveness and Safety of Magnesium Replacement in Critically Ill Patients Admitted to the Medical Intensive Care Unit in an Academic Medical Center: A Retrospective, Cohort Study. J Intensive Care Med. 2019 Nov-Dec;34(11-12):967-972. doi: 10.1177/0885066617720631. Epub 2017 Jul 13.
  PMID: 28703019
  citation: Yamaguchi H, Shimada H, Yoshita K, Tsubata Y, Ikarashi K, Morioka T, Saito N, Sakai S, Narita I. Severe hypermagnesemia induced by magnesium oxide ingestion: a case series. CEN Case Rep. 2019 Feb;8(1):31-37. doi: 10.1007/s13730-018-0359-5. Epub 2018 Aug 22.
  PMID: 30136128
  citation: Kobelt P, Burke K, Renker P. Evaluation of a standardized sedation assessment for opioid administration in the post anesthesia care unit. Pain Manag Nurs. 2014 Sep;15(3):672-81. doi: 10.1016/j.pmn.2013.11.002. Epub 2014 Jan 22.
  PMID: 24461253
  citation: BELLVILLE JW, BROSS ID, HOWLAND WS. A method for the clinical evaluation of antiemetic agents. Anesthesiology. 1959 Nov-Dec;20:753-60. doi: 10.1097/00000542-195911000-00002. No abstract available.
  PMID: 13798617
  citation: Blaine J, Chonchol M, Levi M. Renal control of calcium, phosphate, and magnesium homeostasis. Clin J Am Soc Nephrol. 2015 Jul 7;10(7):1257-72. doi: 10.2215/CJN.09750913. Epub 2014 Oct 6. Erratum In: Clin J Am Soc Nephrol. 2015 Oct 7;10(10):1886-7.
  PMID: 25287933
  responsible party type: Principal Investigator
  investigator affiliation: Tribhuvan University Teaching Hospital, Institute Of Medicine.
  investigator full name: Priyanka Dahal
  investigator title: MD Resident- Anaesthesiology
  mesh term: Pain, Postoperative
  mesh term: Magnesium Sulfate
  sharing ipd: No