<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/NCT02999126</url>
  </required_header>
  <id_info>
    <org_study_id>2884</org_study_id>
    <nct_id>NCT02999126</nct_id>
  </id_info>
  <brief_title>Slow Stepwise Propofol TCI Induction for Titration Anesthesia Maintenance</brief_title>
  <acronym>(TITINDUC)</acronym>
  <official_title>Slow Stepwise Propofol TCI Induction for Titration Anesthesia Maintenance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Italiano de Buenos Aires</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Italiano de Buenos Aires</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if a slow stepwise propofol TCI induction with&#xD;
      Marsh model (Ke0 0.26), allows for an accurate estimation of the effect site concentration&#xD;
      required for maintenance of the general anesthesia, with propofol and remifentanil, in adult&#xD;
      populations older and younger than 65 years of age.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction: Currently, propofol is the most widely used intravenous anesthetic drug that is&#xD;
      able to provide a safe general anesthesia. Propofol can be administered by using different&#xD;
      techniques including target controlled infusion (TCI). The ability to maintain the&#xD;
      pharmacological conditions after achieving a predetermined clinical effect is one of the&#xD;
      major advantages of this technique. Although the use of TCI devices has increased in common&#xD;
      clinical practice, whether or not all patients are suitable for TCI remains unclear.&#xD;
      Pharmacological models were created based on information from healthy volunteers which may&#xD;
      not apply for specific clinical conditions resulting either in over- or sub-dosed when using&#xD;
      certain drugs.&#xD;
&#xD;
      It is not only individual variability in the pharmacokinetic (PK) parameters of the&#xD;
      anesthetic that is a clinical problem, but it is also the pharmacodynamic variability. A&#xD;
      previous study showed up to 6 times the inter-individual difference among young volunteers in&#xD;
      loss of consciousness (LOC) and return of consciousness (ROC). In addition, greater&#xD;
      differences may be found in the elderly.&#xD;
&#xD;
      Inaccurate general models require the anesthetic team to manually tailor medication&#xD;
      requirements for each individual based on the desired therapeutic effect.&#xD;
&#xD;
      The purpose of this study is to evaluate if a slow stepwise propofol TCI induction with Marsh&#xD;
      model (Ke0 0.26), assessed by clinical and electroencephalographic parameters, allows for an&#xD;
      accurate estimation of the effect concentration required for hypnosis titration and&#xD;
      maintenance of the general anesthesia, in adult populations older and younger than 65 years&#xD;
      of age.&#xD;
&#xD;
      General Objective&#xD;
&#xD;
      • To establish whether a guided slow stepwise guided propofol induction with TCI represents a&#xD;
      good correlation between the calculated Effect-Site Concentration (Ce) for the loss of&#xD;
      consciousness and the required Ce to maintain a bispectral index (BIS) value between 45 and&#xD;
      65 during anesthesia maintenance in both age populations&#xD;
&#xD;
      Specific Objectives&#xD;
&#xD;
        -  To determine the BIS value achieved with every propofol infusion based on the calculated&#xD;
           Ce for the time of loss of consciousness (TLOC)&#xD;
&#xD;
        -  To compare the drug infused per time unit required for the loss of consciousness in both&#xD;
           groups&#xD;
&#xD;
        -  To compare the time and Ce required to achieve loss of consciousness in both groups&#xD;
&#xD;
        -  To evaluate the impact of remifentanil during hypnosis by using the BIS index&#xD;
&#xD;
      Hypothesis&#xD;
&#xD;
      During a slow stepwise anesthetic induction with TCI using the Marsh Model 4.0, the&#xD;
      calculated Ce for the TLOC is comparable to the Ce required for the maintenance of the&#xD;
      hypnosis during the general anesthesia, overcoming the inter-individual variability.&#xD;
&#xD;
      Methods&#xD;
&#xD;
      Experimental study, prospective clinical trial, phase 4. Each subject will be assigned to the&#xD;
      propofol induction modality as described in the &quot;intervention&quot; section.&#xD;
&#xD;
      Once consciousness has been lost and maintenance target concentration has been established,&#xD;
      manual ventilation will be initiated. Remifentanil TCI 6 ng/ml and a neuromuscular relaxant&#xD;
      will be administered afterwards in order to perform endotracheal intubation. An infusion of&#xD;
      phenylephrine between 0,1 and 0,4 mcg/kg/min will be initiated in order to maintain blood&#xD;
      pressure values within 20% of the baseline value.&#xD;
&#xD;
      Continuous monitoring of BIS will be maintained after remifentanil infusion and intubation.&#xD;
      Three minutes after endotracheal intubation, surgery will be prepared following standard&#xD;
      procedures. BIS, spectrogram, and hemodynamics will be registered every 15 seconds,&#xD;
      continuously, and every 3 minutes during 10 minutes respectively.&#xD;
&#xD;
      Subsequently, propofol Ce at TLOC will be established (if any modifications were necessary&#xD;
      after TLOC) and it will be observed for another 30 minutes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2016</start_date>
  <completion_date type="Anticipated">March 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time that BIS range remains within 45 and 65 after a stepwise TCI titration</measure>
    <time_frame>A 30-minute period, starting 10 minutes after Remifentanil infusion (when propofol and remifentanil plasma-effect compartment equilibration has been reached)</time_frame>
    <description>TCI Effect Site Concentration achieved at LOC, depth of anesthesia will be recorded with BIS bilateral sensor</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time for loss of consciousness</measure>
    <time_frame>Up to First 10 minutes, from start of propofol infusion at time 0 until loss of verbal response</time_frame>
    <description>In seconds, using TCI induction with Marsh 4.0 pharmacokinetic model</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect Site Concentration required for loss of consciousness</measure>
    <time_frame>Up to first 10 minutes. It will be considered the propofol effect site concentration displayed at the moment loss of consciousness is achieved.</time_frame>
    <description>In mcg/ml, using Marsh Pharmacokinetic Model, Ke0 0.26 min-1</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Target Controlled Infusion</condition>
  <condition>Induction of Anesthesia</condition>
  <condition>Bispectral Index</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients &lt; 65 years old Propofol 1% TCI induction using plasma concentration, Marsh model (Ke0=0.26 min-1) at 1 mcg/ml, increasing the target concentration by 0.5 mcg/ml every minute until LOC. Remifentanil TCI 6 ng/ml and a neuromuscular relaxant will be administered afterwards in order to perform endotracheal intubation. CeLOC propofol concentration will be established and it will be observed for another 30 minutes. If BIS &lt;40 or &gt;65 propofol target concentration will be modified by 0,3 mcg/ml.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients ≥ 65 years old Propofol 1% TCI induction using plasma concentration, Marsh model (Ke0=0.26 min-1) at 1 mcg/ml, increasing the target concentration by 0.5 mcg/ml every minute until LOC. Remifentanil TCI 6 ng/ml and a neuromuscular relaxant will be administered afterwards in order to perform endotracheal intubation. CeLOC propofol concentration will be established and it will be observed for another 30 minutes. If BIS &lt;40 or &gt;65 propofol target concentration will be modified by 0,3 mcg/ml.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>Propofol intravenously by a stepwise TCI titration with Marsh pharmacokinetic model</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>Fresofol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Remifentanil Hydrochloride</intervention_name>
    <description>Remifentanil intravenously 6 ng/ml by TCI effect site, 3 min prior to intubation and maintained at that concentration throughout the study. If clinical signs of inadequate analgesia are present, remifentanil target concentration will be increased by 1 ng/ml.</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ASA 1 or 2.&#xD;
&#xD;
          -  Age over 20 years old.&#xD;
&#xD;
          -  Scheduled to undergo elective surgery of minor or medium complexity under general&#xD;
             anesthesia.&#xD;
&#xD;
          -  Regarding cognitive function: subjects will be considered with enough cognitive&#xD;
             function if they are able to read and understand the medical history form by properly&#xD;
             answering medical questions during the preoperative anesthesia assessment and being&#xD;
             also able to sign the informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Obesity (BMI &gt;30).&#xD;
&#xD;
          -  Patients taking benzodiazepines or other central nervous system action drugs.&#xD;
&#xD;
          -  Subjects with psychiatric disorders with or without treatment.&#xD;
&#xD;
          -  Allergies or any adverse reaction to propofol or any of its components (egg lecithin).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hernán Boveri, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Italiano de Buenos Aires</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hernán Boveri, MD</last_name>
    <email>hernan.boveri@hospitalitaliano.org.ar</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hospital Italiano de Buenos Aires</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1181ACH</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hernán Boveri, MD</last_name>
      <phone>+5491132954777</phone>
      <email>hernan.boveri@hospitalitaliano.org.ar</email>
    </contact>
  </location>
  <location_countries>
    <country>Argentina</country>
  </location_countries>
  <reference>
    <citation>Struys M, Versichelen L, Byttebier G, Mortier E, Moerman A, Rolly G. Clinical usefulness of the bispectral index for titrating propofol target effect-site concentration. Anaesthesia. 1998 Jan;53(1):4-12. doi: 10.1111/j.1365-2044.1998.00279.x.</citation>
    <PMID>9505735</PMID>
  </reference>
  <reference>
    <citation>Coppens M, Van Limmen JG, Schnider T, Wyler B, Bonte S, Dewaele F, Struys MM, Vereecke HE. Study of the time course of the clinical effect of propofol compared with the time course of the predicted effect-site concentration: Performance of three pharmacokinetic-dynamic models. Br J Anaesth. 2010 Apr;104(4):452-8. doi: 10.1093/bja/aeq028. Epub 2010 Feb 26. Erratum In: Br J Anaesth. 2019 Feb;122(2):287.</citation>
    <PMID>20190259</PMID>
  </reference>
  <reference>
    <citation>Bienert A, Wiczling P, Grzeskowiak E, Cywinski JB, Kusza K. Potential pitfalls of propofol target controlled infusion delivery related to its pharmacokinetics and pharmacodynamics. Pharmacol Rep. 2012;64(4):782-95. doi: 10.1016/s1734-1140(12)70874-5.</citation>
    <PMID>23087131</PMID>
  </reference>
  <reference>
    <citation>Iwakiri H, Nishihara N, Nagata O, Matsukawa T, Ozaki M, Sessler DI. Individual effect-site concentrations of propofol are similar at loss of consciousness and at awakening. Anesth Analg. 2005 Jan;100(1):107-110. doi: 10.1213/01.ANE.0000139358.15909.EA.</citation>
    <PMID>15616062</PMID>
  </reference>
  <reference>
    <citation>Struys MM, Sahinovic M, Lichtenbelt BJ, Vereecke HE, Absalom AR. Optimizing intravenous drug administration by applying pharmacokinetic/pharmacodynamic concepts. Br J Anaesth. 2011 Jul;107(1):38-47. doi: 10.1093/bja/aer108. Epub 2011 May 30.</citation>
    <PMID>21624964</PMID>
  </reference>
  <reference>
    <citation>Sepulveda PO, Cortinez LI, Recart A, Munoz HR. Predictive ability of propofol effect-site concentrations during fast and slow infusion rates. Acta Anaesthesiol Scand. 2010 Apr;54(4):447-52. doi: 10.1111/j.1399-6576.2009.02183.x. Epub 2009 Dec 14.</citation>
    <PMID>20003124</PMID>
  </reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>December 8, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>February 15, 2020</last_update_submitted>
  <last_update_submitted_qc>February 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Italiano de Buenos Aires</investigator_affiliation>
    <investigator_full_name>Hernan Boveri</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Total Intravenous Anesthesia</keyword>
  <keyword>Titration</keyword>
  <keyword>Target Controlled Infusion</keyword>
  <keyword>Propofol</keyword>
  <keyword>Bispectral index</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Remifentanil</mesh_term>
    <mesh_term>Propofol</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/NCT02999126
org study id: 2884
nct id: NCT02999126
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine if a slow stepwise propofol TCI induction with
      Marsh model (Ke0 0.26), allows for an accurate estimation of the effect site concentration
      required for maintenance of the general anesthesia, with propofol and remifentanil, in adult
      populations older and younger than 65 years of age.
Introduction: Currently, propofol is the most widely used intravenous anesthetic drug that is
      able to provide a safe general anesthesia. Propofol can be administered by using different
      techniques including target controlled infusion (TCI). The ability to maintain the
      pharmacological conditions after achieving a predetermined clinical effect is one of the
      major advantages of this technique. Although the use of TCI devices has increased in common
      clinical practice, whether or not all patients are suitable for TCI remains unclear.
      Pharmacological models were created based on information from healthy volunteers which may
      not apply for specific clinical conditions resulting either in over- or sub-dosed when using
      certain drugs.

      It is not only individual variability in the pharmacokinetic (PK) parameters of the
      anesthetic that is a clinical problem, but it is also the pharmacodynamic variability. A
      previous study showed up to 6 times the inter-individual difference among young volunteers in
      loss of consciousness (LOC) and return of consciousness (ROC). In addition, greater
      differences may be found in the elderly.

      Inaccurate general models require the anesthetic team to manually tailor medication
      requirements for each individual based on the desired therapeutic effect.

      The purpose of this study is to evaluate if a slow stepwise propofol TCI induction with Marsh
      model (Ke0 0.26), assessed by clinical and electroencephalographic parameters, allows for an
      accurate estimation of the effect concentration required for hypnosis titration and
      maintenance of the general anesthesia, in adult populations older and younger than 65 years
      of age.

      General Objective

      • To establish whether a guided slow stepwise guided propofol induction with TCI represents a
      good correlation between the calculated Effect-Site Concentration (Ce) for the loss of
      consciousness and the required Ce to maintain a bispectral index (BIS) value between 45 and
      65 during anesthesia maintenance in both age populations

      Specific Objectives

        -  To determine the BIS value achieved with every propofol infusion based on the calculated
           Ce for the time of loss of consciousness (TLOC)

        -  To compare the drug infused per time unit required for the loss of consciousness in both
           groups

        -  To compare the time and Ce required to achieve loss of consciousness in both groups

        -  To evaluate the impact of remifentanil during hypnosis by using the BIS index

      Hypothesis

      During a slow stepwise anesthetic induction with TCI using the Marsh Model 4.0, the
      calculated Ce for the TLOC is comparable to the Ce required for the maintenance of the
      hypnosis during the general anesthesia, overcoming the inter-individual variability.

      Methods

      Experimental study, prospective clinical trial, phase 4. Each subject will be assigned to the
      propofol induction modality as described in the "intervention" section.

      Once consciousness has been lost and maintenance target concentration has been established,
      manual ventilation will be initiated. Remifentanil TCI 6 ng/ml and a neuromuscular relaxant
      will be administered afterwards in order to perform endotracheal intubation. An infusion of
      phenylephrine between 0,1 and 0,4 mcg/kg/min will be initiated in order to maintain blood
      pressure values within 20% of the baseline value.

      Continuous monitoring of BIS will be maintained after remifentanil infusion and intubation.
      Three minutes after endotracheal intubation, surgery will be prepared following standard
      procedures. BIS, spectrogram, and hemodynamics will be registered every 15 seconds,
      continuously, and every 3 minutes during 10 minutes respectively.

      Subsequently, propofol Ce at TLOC will be established (if any modifications were necessary
      after TLOC) and it will be observed for another 30 minutes.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Single (Participant)
measure: Time that BIS range remains within 45 and 65 after a stepwise TCI titration
time frame: A 30-minute period, starting 10 minutes after Remifentanil infusion (when propofol and remifentanil plasma-effect compartment equilibration has been reached)
description: TCI Effect Site Concentration achieved at LOC, depth of anesthesia will be recorded with BIS bilateral sensor
measure: Time for loss of consciousness
time frame: Up to First 10 minutes, from start of propofol infusion at time 0 until loss of verbal response
description: In seconds, using TCI induction with Marsh 4.0 pharmacokinetic model
measure: Effect Site Concentration required for loss of consciousness
time frame: Up to first 10 minutes. It will be considered the propofol effect site concentration displayed at the moment loss of consciousness is achieved.
description: In mcg/ml, using Marsh Pharmacokinetic Model, Ke0 0.26 min-1
arm group label: Group 1
arm group type: Experimental
description: Patients < 65 years old Propofol 1% TCI induction using plasma concentration, Marsh model (Ke0=0.26 min-1) at 1 mcg/ml, increasing the target concentration by 0.5 mcg/ml every minute until LOC. Remifentanil TCI 6 ng/ml and a neuromuscular relaxant will be administered afterwards in order to perform endotracheal intubation. CeLOC propofol concentration will be established and it will be observed for another 30 minutes. If BIS <40 or >65 propofol target concentration will be modified by 0,3 mcg/ml.
arm group label: Group 2
arm group type: Experimental
description: Patients ≥ 65 years old Propofol 1% TCI induction using plasma concentration, Marsh model (Ke0=0.26 min-1) at 1 mcg/ml, increasing the target concentration by 0.5 mcg/ml every minute until LOC. Remifentanil TCI 6 ng/ml and a neuromuscular relaxant will be administered afterwards in order to perform endotracheal intubation. CeLOC propofol concentration will be established and it will be observed for another 30 minutes. If BIS <40 or >65 propofol target concentration will be modified by 0,3 mcg/ml.
intervention type: Drug
intervention name: Propofol
description: Propofol intravenously by a stepwise TCI titration with Marsh pharmacokinetic model
arm group label: Group 1
arm group label: Group 2
other name: Fresofol
intervention type: Drug
intervention name: Remifentanil Hydrochloride
description: Remifentanil intravenously 6 ng/ml by TCI effect site, 3 min prior to intubation and maintained at that concentration throughout the study. If clinical signs of inadequate analgesia are present, remifentanil target concentration will be increased by 1 ng/ml.
arm group label: Group 1
arm group label: Group 2
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Hernán Boveri, MD
role: Principal Investigator
affiliation: Hospital Italiano de Buenos Aires
last name: Hernán Boveri, MD
email: hernan.boveri@hospitalitaliano.org.ar
facility: 
status: Recruiting
contact: 
country: Argentina
citation: Struys M, Versichelen L, Byttebier G, Mortier E, Moerman A, Rolly G. Clinical usefulness of the bispectral index for titrating propofol target effect-site concentration. Anaesthesia. 1998 Jan;53(1):4-12. doi: 10.1111/j.1365-2044.1998.00279.x.
PMID: 9505735
citation: Coppens M, Van Limmen JG, Schnider T, Wyler B, Bonte S, Dewaele F, Struys MM, Vereecke HE. Study of the time course of the clinical effect of propofol compared with the time course of the predicted effect-site concentration: Performance of three pharmacokinetic-dynamic models. Br J Anaesth. 2010 Apr;104(4):452-8. doi: 10.1093/bja/aeq028. Epub 2010 Feb 26. Erratum In: Br J Anaesth. 2019 Feb;122(2):287.
PMID: 20190259
citation: Bienert A, Wiczling P, Grzeskowiak E, Cywinski JB, Kusza K. Potential pitfalls of propofol target controlled infusion delivery related to its pharmacokinetics and pharmacodynamics. Pharmacol Rep. 2012;64(4):782-95. doi: 10.1016/s1734-1140(12)70874-5.
PMID: 23087131
citation: Iwakiri H, Nishihara N, Nagata O, Matsukawa T, Ozaki M, Sessler DI. Individual effect-site concentrations of propofol are similar at loss of consciousness and at awakening. Anesth Analg. 2005 Jan;100(1):107-110. doi: 10.1213/01.ANE.0000139358.15909.EA.
PMID: 15616062
citation: Struys MM, Sahinovic M, Lichtenbelt BJ, Vereecke HE, Absalom AR. Optimizing intravenous drug administration by applying pharmacokinetic/pharmacodynamic concepts. Br J Anaesth. 2011 Jul;107(1):38-47. doi: 10.1093/bja/aer108. Epub 2011 May 30.
PMID: 21624964
citation: Sepulveda PO, Cortinez LI, Recart A, Munoz HR. Predictive ability of propofol effect-site concentrations during fast and slow infusion rates. Acta Anaesthesiol Scand. 2010 Apr;54(4):447-52. doi: 10.1111/j.1399-6576.2009.02183.x. Epub 2009 Dec 14.
PMID: 20003124
responsible party type: Principal Investigator
investigator affiliation: Hospital Italiano de Buenos Aires
investigator full name: Hernan Boveri
investigator title: MD
mesh term: Remifentanil
mesh term: Propofol
sharing ipd: No