<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/NCT01677650</url>
  </required_header>
  <id_info>
    <org_study_id>STU00064915</org_study_id>
    <nct_id>NCT01677650</nct_id>
  </id_info>
  <brief_title>Pharmacogenomics of Methadone in Spine Fusion Surgery</brief_title>
  <official_title>The Influence of Pharmacogenetics on Methadone Dose, Safety, and Outcomes After Spine Fusion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Northwestern University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Northwestern University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall objective is to develop a patient oriented research program to efficiently&#xD;
      evaluate the effects of pharmacogenetic variants on the dose-response relationships and&#xD;
      safety of opioids and non-opioid analgesics. If an opioid regimen can be created that&#xD;
      produces excellent opioid analgesia with minimal toxicity related to supratherapeutic opioid&#xD;
      concentrations (i.e., ventilatory depression), other non-opioid analgesics (i.e.,&#xD;
      gabapentin/pregabalin, ketamine, lidocaine, cyclooxygenase inhibitors, etc.) that may&#xD;
      decrease preoperative opioid requirements can be more efficiently and safely evaluated. These&#xD;
      interventions may limit the opioid related toxicities related to effect site concentrations&#xD;
      that are below those required when opioids are the predominant analgesic, such as opioid&#xD;
      related ileus. Methadone's slow elimination clearance and limited pharmacokinetic drug-drug&#xD;
      interactions make it an attractive perioperative opioid. The first step towards personalized&#xD;
      opioid analgesia is to determine the effect of common pharmacogenetic variants that affect&#xD;
      either methadone metabolism (CYP2B6) or opioid elimination.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is being done to find the optimal dose of methadone (a long acting pain&#xD;
      medication) that decreases the amount of pain that people have after spine surgery. Five&#xD;
      different doses of methadone will be compared to each other, while keeping the remainder of&#xD;
      the anesthetic routine for surgery. The investigators will determine the analgesic&#xD;
      dose-response of methadone. The investigators will also determine the effect of methadone on&#xD;
      the incidence of opioid related side effects, the quality of outcome of recovery, and the&#xD;
      change in the 3-month opioid use.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Investigator moved to new institution&#xD;
  </why_stopped>
  <start_date>March 2014</start_date>
  <completion_date type="Anticipated">January 2015</completion_date>
  <primary_completion_date type="Anticipated">January 2015</primary_completion_date>
  <phase>Phase 1</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time until initial request for postoperative analgesic.</measure>
    <time_frame>60 minutes after extubation, 24, 48, and 72 hours after methadone administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The determination of minimum effective analgesic concentration of methadone.</measure>
    <time_frame>60 minutes after extubation, 24, 48, and 72 hours after methadone administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative pain at rest and with movement (numerical rating scale, NRS)</measure>
    <time_frame>60 minutes after extubation, 24, 48, and 72 hours after methadone administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of occurrences of ventilatory depression during each evaluation interval</measure>
    <time_frame>60 minutes after extubation, 24, 48, and 72 hours after methadone administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nausea and vomiting: number of rescue antiemetic doses and episodes of emesis</measure>
    <time_frame>60 minutes after extubation, 24, 48, and 72 hours after methadone administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of sedation (modified Observer's Assessment of Alertness and Sedation Scale, modified OAA/S scale)</measure>
    <time_frame>60 minutes after extubation, 24, 48, and 72 hours after methadone administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurence of pruritis</measure>
    <time_frame>60 minutes after extubation, 24, 48, and 72 hours after methadone administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Algometry to assess pain tolerance</measure>
    <time_frame>Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of bother associated with opioid-related adverse effects: Opioid-related Symptom Distress Scale (OR-SDS)</measure>
    <time_frame>24, 48, and 72 hours after methadone administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Recovery: Quality of Recovery-40 score</measure>
    <time_frame>24, 48, and 72 hours after methadone administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient analgesic satisfaction</measure>
    <time_frame>24, 48, and 72 hours after methadone administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of back condition pre and post-operatively</measure>
    <time_frame>Pre-operatively, 6 weeks and 3 months post-operatively</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of common opioid related metabolic pathway polymorphisms on methadone's dose response relationships for analgesia and side effects</measure>
    <time_frame>Preoperatively</time_frame>
    <description>CYP2B6 Polymorphism effect on&#xD;
Time to first request for analgesia&#xD;
Secondary outcomes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pupillometry for assessment of sedation</measure>
    <time_frame>Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Scoliosis</condition>
  <condition>Kyphosis</condition>
  <arm_group>
    <arm_group_label>Methadone 0.5 mg/kg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Methadone 0.5 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Methadone 0.4 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Methadone 0.4 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Methadone 0.3 mg/kg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Methadone 0.3 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Methadone 0.2 mg/kg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Methadone 0.2 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Methadone 0.15 mg/kg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Methadone 0.15 mg/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methadone</intervention_name>
    <description>Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg</description>
    <arm_group_label>Methadone 0.15 mg/kg</arm_group_label>
    <arm_group_label>Methadone 0.2 mg/kg</arm_group_label>
    <arm_group_label>Methadone 0.3 mg/kg</arm_group_label>
    <arm_group_label>Methadone 0.4 mg/kg</arm_group_label>
    <arm_group_label>Methadone 0.5 mg/kg</arm_group_label>
    <other_name>Dolophine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ASA physical status I, II, and III&#xD;
&#xD;
          -  male and non-pregnant female&#xD;
&#xD;
          -  English-speaking&#xD;
&#xD;
          -  undergoing elective &lt; 3 vertebral level lumbar spine fusion (with and without&#xD;
             interbody fusion)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of more than the equivalent of 20 mg of IV morphine/24 hr in the past 2 weeks&#xD;
&#xD;
          -  history of substance abuse at any time in the past&#xD;
&#xD;
          -  known QT prolongation&#xD;
&#xD;
          -  Non-elective operations (i.e., cancer or trauma)&#xD;
&#xD;
          -  severe hepatic impairment (serum albumin &lt;3.0 g/dL, history of liver disease)&#xD;
&#xD;
          -  pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dhanesh K. Gupta, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University Feinberg School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northwestern Memorial Hospital</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Rajaee SS, Bae HW, Kanim LE, Delamarter RB. Spinal fusion in the United States: analysis of trends from 1998 to 2008. Spine (Phila Pa 1976). 2012 Jan 1;37(1):67-76. doi: 10.1097/BRS.0b013e31820cccfb.</citation>
    <PMID>21311399</PMID>
  </reference>
  <reference>
    <citation>Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA. 1995 Dec 20;274(23):1870-3.</citation>
    <PMID>7500538</PMID>
  </reference>
  <reference>
    <citation>Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.</citation>
    <PMID>20418538</PMID>
  </reference>
  <reference>
    <citation>Upton RN, Semple TJ, Macintyre PE. Pharmacokinetic optimisation of opioid treatment in acute pain therapy. Clin Pharmacokinet. 1997 Sep;33(3):225-44. doi: 10.2165/00003088-199733030-00005.</citation>
    <PMID>9314613</PMID>
  </reference>
  <reference>
    <citation>Taylor S, Kirton OC, Staff I, Kozol RA. Postoperative day one: a high risk period for respiratory events. Am J Surg. 2005 Nov;190(5):752-6. doi: 10.1016/j.amjsurg.2005.07.015.</citation>
    <PMID>16226953</PMID>
  </reference>
  <reference>
    <citation>Taylor S, Voytovich AE, Kozol RA. Has the pendulum swung too far in postoperative pain control? Am J Surg. 2003 Nov;186(5):472-5. doi: 10.1016/j.amjsurg.2003.07.021.</citation>
    <PMID>14599609</PMID>
  </reference>
  <reference>
    <citation>Liu N, Kuhlman G, Dalibon N, Moutafis M, Levron JC, Fischler M. A randomized, double-blinded comparison of intrathecal morphine, sufentanil and their combination versus IV morphine patient-controlled analgesia for postthoracotomy pain. Anesth Analg. 2001 Jan;92(1):31-6. doi: 10.1097/00000539-200101000-00007.</citation>
    <PMID>11133596</PMID>
  </reference>
  <reference>
    <citation>Joris J, Kaba A, Lamy M. Transition between anesthesia and post-operative analgesia: relevance of intra-operative administration of analgesics. Acta Anaesthesiol Belg. 2001;52(3):271-9.</citation>
    <PMID>11732383</PMID>
  </reference>
  <reference>
    <citation>Carroll IR, Angst MS, Clark JD. Management of perioperative pain in patients chronically consuming opioids. Reg Anesth Pain Med. 2004 Nov-Dec;29(6):576-91. doi: 10.1016/j.rapm.2004.06.009.</citation>
    <PMID>15635517</PMID>
  </reference>
  <reference>
    <citation>Yaksh TL, Hua XY, Kalcheva I, Nozaki-Taguchi N, Marsala M. The spinal biology in humans and animals of pain states generated by persistent small afferent input. Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7680-6. doi: 10.1073/pnas.96.14.7680.</citation>
    <PMID>10393880</PMID>
  </reference>
  <reference>
    <citation>Parker RK, Holtmann B, White PF. Effects of a nighttime opioid infusion with PCA therapy on patient comfort and analgesic requirements after abdominal hysterectomy. Anesthesiology. 1992 Mar;76(3):362-7. doi: 10.1097/00000542-199203000-00007.</citation>
    <PMID>1539846</PMID>
  </reference>
  <reference>
    <citation>Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67. doi: 10.1097/00000542-198212000-00005. No abstract available.</citation>
    <PMID>6128949</PMID>
  </reference>
  <reference>
    <citation>Chui PT, Gin T. A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. Anaesth Intensive Care. 1992 Feb;20(1):46-51. doi: 10.1177/0310057X9202000109.</citation>
    <PMID>1609941</PMID>
  </reference>
  <reference>
    <citation>van Dorp EL, Kest B, Kowalczyk WJ, Morariu AM, Waxman AR, Arout CA, Dahan A, Sarton EY. Morphine-6beta-glucuronide rapidly increases pain sensitivity independently of opioid receptor activity in mice and humans. Anesthesiology. 2009 Jun;110(6):1356-63. doi: 10.1097/ALN.0b013e3181a105de.</citation>
    <PMID>19461298</PMID>
  </reference>
  <reference>
    <citation>Egan TD, Huizinga B, Gupta SK, Jaarsma RL, Sperry RJ, Yee JB, Muir KT. Remifentanil pharmacokinetics in obese versus lean patients. Anesthesiology. 1998 Sep;89(3):562-73. doi: 10.1097/00000542-199809000-00004.</citation>
    <PMID>9743391</PMID>
  </reference>
  <reference>
    <citation>Lemmens HJ, Brodsky JB, Bernstein DP. Estimating ideal body weight--a new formula. Obes Surg. 2005 Aug;15(7):1082-3. doi: 10.1381/0960892054621350.</citation>
    <PMID>16105412</PMID>
  </reference>
  <reference>
    <citation>Bowdle TA, Even A, Shen DD, Swardstrom M. Methadone for the induction of anesthesia: plasma histamine concentration, arterial blood pressure, and heart rate. Anesth Analg. 2004 Jun;98(6):1692-1697. doi: 10.1213/01.ANE.0000114085.20751.20.</citation>
    <PMID>15155330</PMID>
  </reference>
  <reference>
    <citation>Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, Schwam EM, Siegel JL. Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol. 1990 Aug;10(4):244-51.</citation>
    <PMID>2286697</PMID>
  </reference>
  <reference>
    <citation>Apfelbaum JL, Gan TJ, Zhao S, Hanna DB, Chen C. Reliability and validity of the perioperative opioid-related symptom distress scale. Anesth Analg. 2004 Sep;99(3):699-709. doi: 10.1213/01.ANE.0000133143.60584.38.</citation>
    <PMID>15333398</PMID>
  </reference>
  <reference>
    <citation>Myles PS, Hunt JO, Fletcher H. Measuring health status (quality of recovery?) after anesthesia and surgery. Anesth Analg. 2001 Jan;92(1):281. doi: 10.1097/00000539-200101000-00062. No abstract available.</citation>
    <PMID>11133650</PMID>
  </reference>
  <reference>
    <citation>Myles PS, Hunt JO, Nightingale CE, Fletcher H, Beh T, Tanil D, Nagy A, Rubinstein A, Ponsford JL. Development and psychometric testing of a quality of recovery score after general anesthesia and surgery in adults. Anesth Analg. 1999 Jan;88(1):83-90. doi: 10.1097/00000539-199901000-00016.</citation>
    <PMID>9895071</PMID>
  </reference>
  <reference>
    <citation>Chou WY, Wang CH, Liu PH, Liu CC, Tseng CC, Jawan B. Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Anesthesiology. 2006 Aug;105(2):334-7. doi: 10.1097/00000542-200608000-00016.</citation>
    <PMID>16871067</PMID>
  </reference>
  <reference>
    <citation>Romberg RR, Olofsen E, Bijl H, Taschner PE, Teppema LJ, Sarton EY, van Kleef JW, Dahan A. Polymorphism of mu-opioid receptor gene (OPRM1:c.118A&gt;G) does not protect against opioid-induced respiratory depression despite reduced analgesic response. Anesthesiology. 2005 Mar;102(3):522-30. doi: 10.1097/00000542-200503000-00008.</citation>
    <PMID>15731588</PMID>
  </reference>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>August 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <last_update_submitted>April 21, 2015</last_update_submitted>
  <last_update_submitted_qc>April 21, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 22, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Northwestern University</investigator_affiliation>
    <investigator_full_name>Dhanesh Gupta</investigator_full_name>
    <investigator_title>Associate Professor of Anesthesiology &amp; Neurological Surgery</investigator_title>
  </responsible_party>
  <keyword>Spinal Fusion</keyword>
  <keyword>Opioid Analgesia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Scoliosis</mesh_term>
    <mesh_term>Kyphosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methadone</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01677650
org study id: STU00064915
nct id: NCT01677650
lead sponsor: 
has dmc: No
The overall objective is to develop a patient oriented research program to efficiently
      evaluate the effects of pharmacogenetic variants on the dose-response relationships and
      safety of opioids and non-opioid analgesics. If an opioid regimen can be created that
      produces excellent opioid analgesia with minimal toxicity related to supratherapeutic opioid
      concentrations (i.e., ventilatory depression), other non-opioid analgesics (i.e.,
      gabapentin/pregabalin, ketamine, lidocaine, cyclooxygenase inhibitors, etc.) that may
      decrease preoperative opioid requirements can be more efficiently and safely evaluated. These
      interventions may limit the opioid related toxicities related to effect site concentrations
      that are below those required when opioids are the predominant analgesic, such as opioid
      related ileus. Methadone's slow elimination clearance and limited pharmacokinetic drug-drug
      interactions make it an attractive perioperative opioid. The first step towards personalized
      opioid analgesia is to determine the effect of common pharmacogenetic variants that affect
      either methadone metabolism (CYP2B6) or opioid elimination.
This study is being done to find the optimal dose of methadone (a long acting pain
      medication) that decreases the amount of pain that people have after spine surgery. Five
      different doses of methadone will be compared to each other, while keeping the remainder of
      the anesthetic routine for surgery. The investigators will determine the analgesic
      dose-response of methadone. The investigators will also determine the effect of methadone on
      the incidence of opioid related side effects, the quality of outcome of recovery, and the
      change in the 3-month opioid use.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time until initial request for postoperative analgesic.
time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: The determination of minimum effective analgesic concentration of methadone.
time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: Postoperative pain at rest and with movement (numerical rating scale, NRS)
time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: The number of occurrences of ventilatory depression during each evaluation interval
time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: Nausea and vomiting: number of rescue antiemetic doses and episodes of emesis
time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: Level of sedation (modified Observer's Assessment of Alertness and Sedation Scale, modified OAA/S scale)
time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: Occurence of pruritis
time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: Algometry to assess pain tolerance
time frame: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: Degree of bother associated with opioid-related adverse effects: Opioid-related Symptom Distress Scale (OR-SDS)
time frame: 24, 48, and 72 hours after methadone administration
measure: Quality of Recovery: Quality of Recovery-40 score
time frame: 24, 48, and 72 hours after methadone administration
measure: Patient analgesic satisfaction
time frame: 24, 48, and 72 hours after methadone administration
measure: Assessment of back condition pre and post-operatively
time frame: Pre-operatively, 6 weeks and 3 months post-operatively
measure: Effects of common opioid related metabolic pathway polymorphisms on methadone's dose response relationships for analgesia and side effects
time frame: Preoperatively
description: CYP2B6 Polymorphism effect on
Time to first request for analgesia
Secondary outcomes
measure: Pupillometry for assessment of sedation
time frame: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
arm group label: Methadone 0.5 mg/kg
arm group type: Active Comparator
description: Methadone 0.5 mg/kg
arm group label: Methadone 0.4 mg/kg
arm group type: Experimental
description: Methadone 0.4 mg/kg
arm group label: Methadone 0.3 mg/kg
arm group type: Active Comparator
description: Methadone 0.3 mg/kg
arm group label: Methadone 0.2 mg/kg
arm group type: Active Comparator
description: Methadone 0.2 mg/kg
arm group label: Methadone 0.15 mg/kg
arm group type: Active Comparator
description: Methadone 0.15 mg/kg
intervention type: Drug
intervention name: Methadone
description: Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg
arm group label: Methadone 0.15 mg/kg
arm group label: Methadone 0.2 mg/kg
arm group label: Methadone 0.3 mg/kg
arm group label: Methadone 0.4 mg/kg
arm group label: Methadone 0.5 mg/kg
other name: Dolophine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Dhanesh K. Gupta, M.D.
role: Principal Investigator
affiliation: Northwestern University Feinberg School of Medicine
facility: 
country: United States
citation: Rajaee SS, Bae HW, Kanim LE, Delamarter RB. Spinal fusion in the United States: analysis of trends from 1998 to 2008. Spine (Phila Pa 1976). 2012 Jan 1;37(1):67-76. doi: 10.1097/BRS.0b013e31820cccfb.
PMID: 21311399
citation: Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA. 1995 Dec 20;274(23):1870-3.
PMID: 7500538
citation: Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.
PMID: 20418538
citation: Upton RN, Semple TJ, Macintyre PE. Pharmacokinetic optimisation of opioid treatment in acute pain therapy. Clin Pharmacokinet. 1997 Sep;33(3):225-44. doi: 10.2165/00003088-199733030-00005.
PMID: 9314613
citation: Taylor S, Kirton OC, Staff I, Kozol RA. Postoperative day one: a high risk period for respiratory events. Am J Surg. 2005 Nov;190(5):752-6. doi: 10.1016/j.amjsurg.2005.07.015.
PMID: 16226953
citation: Taylor S, Voytovich AE, Kozol RA. Has the pendulum swung too far in postoperative pain control? Am J Surg. 2003 Nov;186(5):472-5. doi: 10.1016/j.amjsurg.2003.07.021.
PMID: 14599609
citation: Liu N, Kuhlman G, Dalibon N, Moutafis M, Levron JC, Fischler M. A randomized, double-blinded comparison of intrathecal morphine, sufentanil and their combination versus IV morphine patient-controlled analgesia for postthoracotomy pain. Anesth Analg. 2001 Jan;92(1):31-6. doi: 10.1097/00000539-200101000-00007.
PMID: 11133596
citation: Joris J, Kaba A, Lamy M. Transition between anesthesia and post-operative analgesia: relevance of intra-operative administration of analgesics. Acta Anaesthesiol Belg. 2001;52(3):271-9.
PMID: 11732383
citation: Carroll IR, Angst MS, Clark JD. Management of perioperative pain in patients chronically consuming opioids. Reg Anesth Pain Med. 2004 Nov-Dec;29(6):576-91. doi: 10.1016/j.rapm.2004.06.009.
PMID: 15635517
citation: Yaksh TL, Hua XY, Kalcheva I, Nozaki-Taguchi N, Marsala M. The spinal biology in humans and animals of pain states generated by persistent small afferent input. Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7680-6. doi: 10.1073/pnas.96.14.7680.
PMID: 10393880
citation: Parker RK, Holtmann B, White PF. Effects of a nighttime opioid infusion with PCA therapy on patient comfort and analgesic requirements after abdominal hysterectomy. Anesthesiology. 1992 Mar;76(3):362-7. doi: 10.1097/00000542-199203000-00007.
PMID: 1539846
citation: Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67. doi: 10.1097/00000542-198212000-00005. No abstract available.
PMID: 6128949
citation: Chui PT, Gin T. A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. Anaesth Intensive Care. 1992 Feb;20(1):46-51. doi: 10.1177/0310057X9202000109.
PMID: 1609941
citation: van Dorp EL, Kest B, Kowalczyk WJ, Morariu AM, Waxman AR, Arout CA, Dahan A, Sarton EY. Morphine-6beta-glucuronide rapidly increases pain sensitivity independently of opioid receptor activity in mice and humans. Anesthesiology. 2009 Jun;110(6):1356-63. doi: 10.1097/ALN.0b013e3181a105de.
PMID: 19461298
citation: Egan TD, Huizinga B, Gupta SK, Jaarsma RL, Sperry RJ, Yee JB, Muir KT. Remifentanil pharmacokinetics in obese versus lean patients. Anesthesiology. 1998 Sep;89(3):562-73. doi: 10.1097/00000542-199809000-00004.
PMID: 9743391
citation: Lemmens HJ, Brodsky JB, Bernstein DP. Estimating ideal body weight--a new formula. Obes Surg. 2005 Aug;15(7):1082-3. doi: 10.1381/0960892054621350.
PMID: 16105412
citation: Bowdle TA, Even A, Shen DD, Swardstrom M. Methadone for the induction of anesthesia: plasma histamine concentration, arterial blood pressure, and heart rate. Anesth Analg. 2004 Jun;98(6):1692-1697. doi: 10.1213/01.ANE.0000114085.20751.20.
PMID: 15155330
citation: Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, Schwam EM, Siegel JL. Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol. 1990 Aug;10(4):244-51.
PMID: 2286697
citation: Apfelbaum JL, Gan TJ, Zhao S, Hanna DB, Chen C. Reliability and validity of the perioperative opioid-related symptom distress scale. Anesth Analg. 2004 Sep;99(3):699-709. doi: 10.1213/01.ANE.0000133143.60584.38.
PMID: 15333398
citation: Myles PS, Hunt JO, Fletcher H. Measuring health status (quality of recovery?) after anesthesia and surgery. Anesth Analg. 2001 Jan;92(1):281. doi: 10.1097/00000539-200101000-00062. No abstract available.
PMID: 11133650
citation: Myles PS, Hunt JO, Nightingale CE, Fletcher H, Beh T, Tanil D, Nagy A, Rubinstein A, Ponsford JL. Development and psychometric testing of a quality of recovery score after general anesthesia and surgery in adults. Anesth Analg. 1999 Jan;88(1):83-90. doi: 10.1097/00000539-199901000-00016.
PMID: 9895071
citation: Chou WY, Wang CH, Liu PH, Liu CC, Tseng CC, Jawan B. Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Anesthesiology. 2006 Aug;105(2):334-7. doi: 10.1097/00000542-200608000-00016.
PMID: 16871067
citation: Romberg RR, Olofsen E, Bijl H, Taschner PE, Teppema LJ, Sarton EY, van Kleef JW, Dahan A. Polymorphism of mu-opioid receptor gene (OPRM1:c.118A>G) does not protect against opioid-induced respiratory depression despite reduced analgesic response. Anesthesiology. 2005 Mar;102(3):522-30. doi: 10.1097/00000542-200503000-00008.
PMID: 15731588
responsible party type: Principal Investigator
investigator affiliation: Northwestern University
investigator full name: Dhanesh Gupta
investigator title: Associate Professor of Anesthesiology & Neurological Surgery
mesh term: Scoliosis
mesh term: Kyphosis
mesh term: Methadone