<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/NCT03024931</url>
  </required_header>
  <id_info>
    <org_study_id>qw</org_study_id>
    <nct_id>NCT03024931</nct_id>
  </id_info>
  <brief_title>Metabolic Rate in Burns</brief_title>
  <acronym>MrBurn</acronym>
  <official_title>In Vivo Cellular and Physiological Response to Severe Burns Injuries</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chelsea and Westminster NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chelsea and Westminster NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Severe burn patients are some of the most challenging critically ill patients with an extreme&#xD;
      and continuous state of physiological stress. Patients tends to stay for a long period of&#xD;
      time in intensive care unit to treat burns as well as dealing with complications that arises&#xD;
      from the initial burns injury. Severe burns patients are notoriously known to loose weight.&#xD;
      The word 'catabolism' is used medically. This theory of catabolism after a trauma was&#xD;
      hypothesised in 1942 by Professor Curthberston and based on animal models. Since this date,&#xD;
      despite medical technological advancement, there has been no research that confirms Professor&#xD;
      Curthberston's theory. Investigators still do not know the exact mechanism by which the body&#xD;
      changes from conserving energy to becoming catabolic. Furthermore, it remains unclear whether&#xD;
      this change in catabolism is necessary to heal from burns injury.&#xD;
&#xD;
      This theoretical catabolism in burns patients is currently treated with nutritional&#xD;
      supplement, use of medications including beta-blockers (suppresses heart rate and decreases&#xD;
      blood pressure) and oxandrolone (formula which is similar to testosterone to build up&#xD;
      muscles).&#xD;
&#xD;
      There are evidences to suggest that increase in weight loss worsens the outcome in burns&#xD;
      injury. Both overfeeding or underfeeding patients can be detrimental. In this research, the&#xD;
      exact changes in metabolic rate will be measured in the first 72 hours of the study using a&#xD;
      calorimetry machine. In addition to the metabolic rate, the response to the heart, liver,&#xD;
      kidneys and hormonal levels will be measured. By looking into these dynamic changes the&#xD;
      investigator will be able to elucidate whether there is a real increase in metabolic rate. If&#xD;
      there is, the investigator would also be able to tell the response of different organs and&#xD;
      whether there are any hormones that could be responsible to inflicting the metabolic changes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Purpose of the study The purpose of this study is to gain a better understanding of the&#xD;
           acute physiological and metabolic changes in severe burns injury. Unless clinicians&#xD;
           understand the physiological effect in burns patients, clinicians are unable to develop&#xD;
           new therapeutic interventions to halt the hyper metabolic changes in burns patient. This&#xD;
           research will be looking into the acute resting basal metabolic changes in severe adult&#xD;
           burns patients by using Quark RMR (indirect calorimetry). This equipment will allow the&#xD;
           investigator to detect the metabolic switch in severe burns patients.&#xD;
&#xD;
           In addition to the metabolic changes, 'Estimated cardiac output monitor' will be placed&#xD;
           in conjunction with calculating the Fick principle. Heart rate and pulse oximeter will&#xD;
           be monitored continuously. These adjuncts will allow the investigator to conclude&#xD;
           whether hyper-metabolism is associated with hyper dynamic cardiovascular response to&#xD;
           burns.&#xD;
&#xD;
           Splanchnic circulation will be monitored using the LiMON indocyanine green test and&#xD;
           intermittent intra-abdominal pressure will be monitored to assess whether there is a&#xD;
           link between the metabolic rate and splanchnic circulation.&#xD;
&#xD;
        2. Objectives&#xD;
&#xD;
             1. Primary Objective:&#xD;
&#xD;
                Identifying the 'Ebb' phase and 'Flow' phase in acute burns injury&#xD;
&#xD;
             2. Secondary Objectives:&#xD;
&#xD;
      1. To establish cardiovascular response to burns in the acute phase.&#xD;
&#xD;
      a. To establish cardiovascular response to hyper-catabolism, using ESCO (estimated cardiac&#xD;
      output) 2. To asses the relationship between the splanchnic circulation and hyper-catabolism&#xD;
      3. To assess the feasibility of performing LiMON test and (Bispectral Index) BIS monitoring&#xD;
      for future (Burns Intensive Care Unit) BICU patients 4. To optimize dietary recommendations&#xD;
      for patients who are suffering from hyper-catabolic state&#xD;
&#xD;
      8. Study Design Summary: This is a prospective, observational study with intensive monitoring&#xD;
      but no experimental intervention&#xD;
&#xD;
      a) Study Site and Duration: This study will be conducted on the adult Burns Intensive Care&#xD;
      Unit (BICU), Chelsea and Westminster Foundation Trust, London, United Kingdom (UK). This is a&#xD;
      tertiary referral hospital serving an area of North West London. The average annual admission&#xD;
      for severe burns to BICU varies form 10 -15 patients. The study will be conducted from&#xD;
      December 2015 to December 2019.&#xD;
&#xD;
      The BICU has facilities for ventilatory support, sedation and surgery of critically ill&#xD;
      patients, with two-bed intensive care unit. Each bed is isolated with three senior trained&#xD;
      intensive care nurses covering 24 hours. Critically ill burns participants will be monitored&#xD;
      continuously by nurses and doctors with the use of non-invasive and invasive monitoring&#xD;
      depending on their clinical needs as per standard clinical care.&#xD;
&#xD;
      f) Procedure&#xD;
&#xD;
      General History and Examination Upon enrolment, full history and examination will be&#xD;
      performed, including detailed assessment of the respiratory system, extent and depth of&#xD;
      burns, neurological examination, cardiovascular examination and excluding other potential&#xD;
      trauma that the participants could have suffered from.&#xD;
&#xD;
      The results will be recorded on a designated record form. Participants will be re-assessed by&#xD;
      a physician or nurse for the duration of continuous monitoring to independently assess blood&#xD;
      pressure, heart rate, respiratory rate, oxygen saturation, cardiac output, Glasgow coma&#xD;
      scale, sedation score, ventilator requirement, urine output, intra-abdominal pressure,&#xD;
      splanchnic circulation, BIS, EEG, nitrogen balance, resting metabolic rate and temperature.&#xD;
&#xD;
      Daily follow up will include assessment for any complications of burns including sepsis,&#xD;
      infection, inhalational injury, suspected Acute Respiratory Distress Syndrome, and suspected&#xD;
      respiratory distress of uncertain aetiology. The decision to obtain imaging or other&#xD;
      investigations to assess such complications will be made by the clinical team and the results&#xD;
      will be archived as source documents.&#xD;
&#xD;
      In addition to above, venous blood sample will be taken to establish on the daily basis to&#xD;
      monitor inflammatory markers, renal, liver, bone marrow function, electrolyte levels. Urinary&#xD;
      nitrogen levels, plasma hormones including Thyroid stimulating hormone, T3, T4, cortisol&#xD;
      levels, insulin, glucagon levels are taken daily. These tests will be completed by the&#xD;
      clinical team.&#xD;
&#xD;
      Regular arterial line gas sample will be taken as guided by the clinical team.&#xD;
&#xD;
      Continuous monitoring Participants will undergo standard electrophysiological monitoring,&#xD;
      cardiovascular monitoring including arterial line blood pressure monitoring, placement of&#xD;
      estimated cardiac output monitoring and intra-abdominal pressure. These devices will be&#xD;
      connected to a portable diagnostic recording system to aid the diagnosis of any physiological&#xD;
      changes that occurs. The system comprises a central device, with a display screen, battery&#xD;
      pack and memory card. The electrophysiological monitoring device will consists or three&#xD;
      electrodes and wires which feeds into the central device ports. The electrodes will be&#xD;
      attached to the participants' forehead; left central and right. The intra-abdominal pressure&#xD;
      device consists of a transducer which is located in the urinary catheter. The wires which are&#xD;
      connected to the transducers are then fed into the central device ports. The continuous&#xD;
      estimated cardiac output monitoring devices consist of three cardiac electrodes, pulse&#xD;
      oximetry device and wires, which are connected to the central device ports. The cardiac&#xD;
      electrodes are placed to the participants' thorax and the pulse oximetry device is attached&#xD;
      to the participants' digit either in the foot or hand.&#xD;
&#xD;
      The following sensors will be applied:&#xD;
&#xD;
        -  Electrocardiogram: recording cardiac electrical activity to give three recorded and&#xD;
           three derived traces&#xD;
&#xD;
        -  Ventilator: recording airflow inhale and exhalation, flow rate, pressure, tidal volume,&#xD;
           peep, type of ventilator mode.&#xD;
&#xD;
        -  Pulse oximeter: recording arterial oxygen saturation and pulse rate The monitoring&#xD;
           system will be applied to the participant once assent is obtained and after the initial&#xD;
           management; drug administration, examination and other investigation are performed by&#xD;
           the clinical team. The sensors will be applied with the goal of recording continuously&#xD;
           for seventy two hours.&#xD;
&#xD;
      Intermittent monitoring Participant will undergo indirect calorimetry monitoring and LIMON&#xD;
      test. Resting metabolic rate will be measured every 12 hourly for 72 hours using indirect&#xD;
      calorimetry with Quark Resting Metabolic Rate (QUARK RMR) (COSMED, Rome, Italy). This device&#xD;
      consist of canopy, ventilator tubing, heat and moisture exchange filter, air sample analyzing&#xD;
      tubes, computer, gas analyzing chamber, calibration gas cylinder, air pump to calibrate the&#xD;
      flow sensor, fuel cell, spirometry and Windows 8.0 computer which has COSMED Quark RMR&#xD;
      software installed.&#xD;
&#xD;
      Participants are either ventilated or awake. Ventilated participants will have a gas&#xD;
      analyzing tubing attached to the heat and moisture exchange filter which is fed unto the gas&#xD;
      analyzing chamber. The flow meter is attached at the exhaust port at the back of the&#xD;
      ventilator.&#xD;
&#xD;
      The measurement is taken until a steady resting state is achieved. This will normally vary&#xD;
      from two minutes to 20 minutes. The results are automatically recorded onto the Quark RMR&#xD;
      software. In order to achieve steady ventilation with little minimum bias flow the&#xD;
      participants' Bispectral index is maintained between forty and sixty using medications such&#xD;
      as propofol, fentanyl, midazolam or clonidine.&#xD;
&#xD;
      Liver and splanchnic circulation will be measured every 6 hourly using LIMON Liver Function&#xD;
      Monitor (Liver Monitor, PULSION Medical Systems, Munich, Germany) The device consist of&#xD;
      sensor, wires and monitor to display the instructions and results. The sensor is attached to&#xD;
      the participants' earlobe, finger tips in the hand or foot. The indocyanine green dye (ICG)&#xD;
      is injected into a vein. The results will be displayed onto the monitor.&#xD;
&#xD;
      If the recording is suboptimal due to loss of sensors or insufficient recording, it will be&#xD;
      repeated.&#xD;
&#xD;
      All of the above equipments and monitoring system will be cleaned and disinfected according&#xD;
      to the manufacturing advice and microbiology team. The standard operating procedures for the&#xD;
      above equipments are described in the appendix.&#xD;
&#xD;
      Cessation of monitoring The recording system, or individual sensors will be removed&#xD;
      immediately if it is required for clinical investigations or interventions. However, it is&#xD;
      anticipated that most investigations and interventions will be able to proceed with the&#xD;
      sensors in place. The device is expected to remain in place during patient re-positioning,&#xD;
      airway management, delivery of oxygen, delivery of oral and IV medication and fluids and most&#xD;
      imaging with the exception of magnetic resonance imaging.&#xD;
&#xD;
      BIS monitoring will be removed in the event of cardio-respiratory arrest. If study clinician&#xD;
      is not present at the time of cardio-respiratory arrest, the monitor will detach without&#xD;
      difficulty and will not impede or delay resuscitation efforts.&#xD;
&#xD;
      Date collection:&#xD;
&#xD;
      In addition to above data, the investigator be collecting the patients' demographics&#xD;
      including apache II scoring, end organ function including liver function, renal function,&#xD;
      haematological status, ventilator settings, arterial gas, urine output and temperature.&#xD;
&#xD;
      9. Data Analysis Analysis of recording Data will be exported from the monitoring devices&#xD;
      after each recording and assessed for adequacy and quality.&#xD;
&#xD;
      All frontal lobe electroencephalogram will be analysed. If there is any EEG finding that are&#xD;
      consist with seizures it will be reviewed by neurophysiologist. All resting metabolic rate&#xD;
      will be plotted against the physiological parameters including splanchnic circulation,&#xD;
      temperature and intra-abdominal pressure. The ECG will be reviewed to assess heart rate,&#xD;
      rhythm and conduction. Invasive blood pressure monitoring device will assess the blood&#xD;
      pressure. Estimated cardiac output monitoring will assess the cardiac output and the trend&#xD;
      over the seventy two hours. Fick principle will be used to calculate the cardiac output using&#xD;
      the data (CaO2 and CVO2) obtained from the Quark RMR.&#xD;
&#xD;
      Any stimulus, airway management, changes in the levels of sedation, return from theatres will&#xD;
      be noted.&#xD;
&#xD;
        1. Statistical Consideration In the view of the complexity of data provided by continuous&#xD;
           monitoring, statistical guidance will be sought at all stages of analysis from the&#xD;
           &quot;Statistician. For the primary end points, the investigator will draw a graph of time&#xD;
           again resting metabolic rate. The precise choice of test will be determined once the&#xD;
           distribution pattern of the data is known. Repeated measure analysis of variance will be&#xD;
           used followed by regression analysis accounted for repeat measures.&#xD;
&#xD;
           In comparing patient specific outcome measures (mortality, requirement for ventilation,&#xD;
           development of complications such as sepsis), participants will be placed into ranked&#xD;
           groups from most to least difference in trend change in resting metabolic rate and&#xD;
           nonparametric analysis will be used to assess the relationship between mortality or&#xD;
           morbidity and resting metabolic rate.&#xD;
&#xD;
        2. Sample Size Justification Primary determinant is expected number of eligible patients&#xD;
           presenting in the duration of study.&#xD;
&#xD;
      Power calculation was completed for the primary outcome measures. In order to conclude to&#xD;
      show that there is an increase in metabolic rate by 200 kcal per day with a power of 0.8, I&#xD;
      will need 8 patients to be able to conclude that there increase in metabolic rate.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Anticipated">December 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Monitor the change in resting metabolic rate over period of time after severe burns injury.</measure>
    <time_frame>Continuous monitoring over 72 hours</time_frame>
    <description>The resting metabolic rate will be measured using Quark Indirect Calorimetry Machine from Cosmed, Italy. The rested metabolic rate will be measured in kilo calories.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Monitor the cardiac output using Fick principle in severe burns</measure>
    <time_frame>The cardiac output will be measured using the fick principle.The cardiac output will be measured at 12th, 24th, 36th, 48th, 60th 72nd hour from the point of the injury. 10 patients will be recruited over a year.</time_frame>
    <description>The cardiac output will be measured in mls.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monitor the splanchnic circulation by measuring the indocyanine green clearance rate.</measure>
    <time_frame>The splanchnic circulation will be measured at 12th, 24th, 36th, 48th, 60th 72nd hour from the point of the injury. 10 patients will be recruited over a year.</time_frame>
    <description>splanchnic circulation will be measured by using Limon machine from Maquet. The plasma clearance rate of indocyanine green will be measured in % per ml.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Burns</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>observational study</intervention_name>
    <description>No intervention</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The investigators plan to study 10 adult patients with severe burns participants within the&#xD;
        first 72 hours of admission to the BICU. Participants will be recruited from the burns&#xD;
        intensive care adult unit (BICU), CWFT, London, UK. Inclusion and exclusion criteria are&#xD;
        below.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, aged 16 years or over&#xD;
&#xD;
          -  Informed, written consent from patient. If the participant is unable to give consent&#xD;
             then assent will be considered.&#xD;
&#xD;
          -  Burns more than 15%&#xD;
&#xD;
          -  Acute presentation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any concern from the clinical team that the application or ongoing presence of the&#xD;
             monitoring device would interfere with optimal patient management.&#xD;
&#xD;
          -  Allergy to adhesives used for monitor leads and belts.&#xD;
&#xD;
          -  Participants below 16 years old&#xD;
&#xD;
          -  Burns less than 5%&#xD;
&#xD;
          -  Conditions that gives an inaccurate calorimetry results&#xD;
&#xD;
          -  Participants needing oxygen concentration more than 60%&#xD;
&#xD;
          -  Participants who have broncho-alveolar fistula&#xD;
&#xD;
          -  Participants with chest drains&#xD;
&#xD;
          -  Airway leak within the ventilated systems&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marcela Vizcaychipi</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chelsea and Westminster NHS trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Asako Shida</last_name>
    <phone>07957497542</phone>
    <email>ashida@imperial.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marcela Vizcaychipi</last_name>
    <phone>02087468903</phone>
    <email>m.vizcaychipi@imperial.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Burn Intensive Care Unit (BICU), Chelsea and Westminster Hospital</name>
      <address>
        <city>London</city>
        <zip>SW10 9NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <results_reference>
    <citation>Herndon DN, Hart DW, Wolf SE, Chinkes DL, Wolfe RR. Reversal of catabolism by beta-blockade after severe burns. N Engl J Med. 2001 Oct 25;345(17):1223-9. doi: 10.1056/NEJMoa010342.</citation>
    <PMID>11680441</PMID>
  </results_reference>
  <results_reference>
    <citation>Huang YS, Yang ZC, Liu XS, Chen FM, He BB, Li A, Crowther RS. Serial experimental and clinical studies on the pathogenesis of multiple organ dysfunction syndrome (MODS) in severe burns. Burns. 1998 Dec;24(8):706-16. doi: 10.1016/s0305-4179(98)00123-5.</citation>
    <PMID>9915670</PMID>
  </results_reference>
  <results_reference>
    <citation>Jeschke MG, Gauglitz GG, Kulp GA, Finnerty CC, Williams FN, Kraft R, Suman OE, Mlcak RP, Herndon DN. Long-term persistance of the pathophysiologic response to severe burn injury. PLoS One. 2011;6(7):e21245. doi: 10.1371/journal.pone.0021245. Epub 2011 Jul 18.</citation>
    <PMID>21789167</PMID>
  </results_reference>
  <results_reference>
    <citation>Jeschke MG, Herndon DN, Wolf SE, DebRoy MA, Rai J, Lichtenbelt BJ, Barrow RE. Recombinant human growth hormone alters acute phase reactant proteins, cytokine expression, and liver morphology in burned rats. J Surg Res. 1999 May 15;83(2):122-9. doi: 10.1006/jsre.1999.5577.</citation>
    <PMID>10329105</PMID>
  </results_reference>
  <results_reference>
    <citation>Kasten KR, Makley AT, Kagan RJ. Update on the critical care management of severe burns. J Intensive Care Med. 2011 Jul-Aug;26(4):223-36. doi: 10.1177/0885066610390869.</citation>
    <PMID>21764766</PMID>
  </results_reference>
  <results_reference>
    <citation>CUTHBERTSON DP. Interrelationship of metabolic changes consequent to injury. Br Med Bull. 1954;10(1):33-7. doi: 10.1093/oxfordjournals.bmb.a069369. No abstract available.</citation>
    <PMID>13126521</PMID>
  </results_reference>
  <results_reference>
    <citation>CUTHBERTSON DP. Nutrition. Annu Rev Med. 1953;4:135-62. doi: 10.1146/annurev.me.04.020153.001031. No abstract available.</citation>
    <PMID>13105270</PMID>
  </results_reference>
  <results_reference>
    <citation>Bell JR, Clark AM, Cuthbertson DP. Experimental traumatic shock. J Physiol. 1938 May 14;92(4):361-70. doi: 10.1113/jphysiol.1938.sp003608. No abstract available.</citation>
    <PMID>16994980</PMID>
  </results_reference>
  <results_reference>
    <citation>Cathcart EP, Cuthbertson DP. The composition and distribution of the fatty substances of the human subject. J Physiol. 1931 Jul 6;72(3):349-60. doi: 10.1113/jphysiol.1931.sp002779. No abstract available.</citation>
    <PMID>16994214</PMID>
  </results_reference>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>December 3, 2016</study_first_submitted>
  <study_first_submitted_qc>January 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 19, 2017</study_first_posted>
  <last_update_submitted>March 12, 2018</last_update_submitted>
  <last_update_submitted_qc>March 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chelsea and Westminster NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>Marcela P. Vizcaychipi</investigator_full_name>
    <investigator_title>Consultant in Anaesthesia and Intensive Care Medicine Honorary Senior Clinical Lecturer Divisional Research Lead for Planned Care Surgery and Clinical Support</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Burns</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>no, we do not plan to share participant data with other researchers.</ipd_description>
  </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/NCT03024931
org study id: qw
nct id: NCT03024931
lead sponsor: 
has dmc: No
Severe burn patients are some of the most challenging critically ill patients with an extreme
      and continuous state of physiological stress. Patients tends to stay for a long period of
      time in intensive care unit to treat burns as well as dealing with complications that arises
      from the initial burns injury. Severe burns patients are notoriously known to loose weight.
      The word 'catabolism' is used medically. This theory of catabolism after a trauma was
      hypothesised in 1942 by Professor Curthberston and based on animal models. Since this date,
      despite medical technological advancement, there has been no research that confirms Professor
      Curthberston's theory. Investigators still do not know the exact mechanism by which the body
      changes from conserving energy to becoming catabolic. Furthermore, it remains unclear whether
      this change in catabolism is necessary to heal from burns injury.

      This theoretical catabolism in burns patients is currently treated with nutritional
      supplement, use of medications including beta-blockers (suppresses heart rate and decreases
      blood pressure) and oxandrolone (formula which is similar to testosterone to build up
      muscles).

      There are evidences to suggest that increase in weight loss worsens the outcome in burns
      injury. Both overfeeding or underfeeding patients can be detrimental. In this research, the
      exact changes in metabolic rate will be measured in the first 72 hours of the study using a
      calorimetry machine. In addition to the metabolic rate, the response to the heart, liver,
      kidneys and hormonal levels will be measured. By looking into these dynamic changes the
      investigator will be able to elucidate whether there is a real increase in metabolic rate. If
      there is, the investigator would also be able to tell the response of different organs and
      whether there are any hormones that could be responsible to inflicting the metabolic changes.
1. Purpose of the study The purpose of this study is to gain a better understanding of the
           acute physiological and metabolic changes in severe burns injury. Unless clinicians
           understand the physiological effect in burns patients, clinicians are unable to develop
           new therapeutic interventions to halt the hyper metabolic changes in burns patient. This
           research will be looking into the acute resting basal metabolic changes in severe adult
           burns patients by using Quark RMR (indirect calorimetry). This equipment will allow the
           investigator to detect the metabolic switch in severe burns patients.

           In addition to the metabolic changes, 'Estimated cardiac output monitor' will be placed
           in conjunction with calculating the Fick principle. Heart rate and pulse oximeter will
           be monitored continuously. These adjuncts will allow the investigator to conclude
           whether hyper-metabolism is associated with hyper dynamic cardiovascular response to
           burns.

           Splanchnic circulation will be monitored using the LiMON indocyanine green test and
           intermittent intra-abdominal pressure will be monitored to assess whether there is a
           link between the metabolic rate and splanchnic circulation.

        2. Objectives

             1. Primary Objective:

                Identifying the 'Ebb' phase and 'Flow' phase in acute burns injury

             2. Secondary Objectives:

      1. To establish cardiovascular response to burns in the acute phase.

      a. To establish cardiovascular response to hyper-catabolism, using ESCO (estimated cardiac
      output) 2. To asses the relationship between the splanchnic circulation and hyper-catabolism
      3. To assess the feasibility of performing LiMON test and (Bispectral Index) BIS monitoring
      for future (Burns Intensive Care Unit) BICU patients 4. To optimize dietary recommendations
      for patients who are suffering from hyper-catabolic state

      8. Study Design Summary: This is a prospective, observational study with intensive monitoring
      but no experimental intervention

      a) Study Site and Duration: This study will be conducted on the adult Burns Intensive Care
      Unit (BICU), Chelsea and Westminster Foundation Trust, London, United Kingdom (UK). This is a
      tertiary referral hospital serving an area of North West London. The average annual admission
      for severe burns to BICU varies form 10 -15 patients. The study will be conducted from
      December 2015 to December 2019.

      The BICU has facilities for ventilatory support, sedation and surgery of critically ill
      patients, with two-bed intensive care unit. Each bed is isolated with three senior trained
      intensive care nurses covering 24 hours. Critically ill burns participants will be monitored
      continuously by nurses and doctors with the use of non-invasive and invasive monitoring
      depending on their clinical needs as per standard clinical care.

      f) Procedure

      General History and Examination Upon enrolment, full history and examination will be
      performed, including detailed assessment of the respiratory system, extent and depth of
      burns, neurological examination, cardiovascular examination and excluding other potential
      trauma that the participants could have suffered from.

      The results will be recorded on a designated record form. Participants will be re-assessed by
      a physician or nurse for the duration of continuous monitoring to independently assess blood
      pressure, heart rate, respiratory rate, oxygen saturation, cardiac output, Glasgow coma
      scale, sedation score, ventilator requirement, urine output, intra-abdominal pressure,
      splanchnic circulation, BIS, EEG, nitrogen balance, resting metabolic rate and temperature.

      Daily follow up will include assessment for any complications of burns including sepsis,
      infection, inhalational injury, suspected Acute Respiratory Distress Syndrome, and suspected
      respiratory distress of uncertain aetiology. The decision to obtain imaging or other
      investigations to assess such complications will be made by the clinical team and the results
      will be archived as source documents.

      In addition to above, venous blood sample will be taken to establish on the daily basis to
      monitor inflammatory markers, renal, liver, bone marrow function, electrolyte levels. Urinary
      nitrogen levels, plasma hormones including Thyroid stimulating hormone, T3, T4, cortisol
      levels, insulin, glucagon levels are taken daily. These tests will be completed by the
      clinical team.

      Regular arterial line gas sample will be taken as guided by the clinical team.

      Continuous monitoring Participants will undergo standard electrophysiological monitoring,
      cardiovascular monitoring including arterial line blood pressure monitoring, placement of
      estimated cardiac output monitoring and intra-abdominal pressure. These devices will be
      connected to a portable diagnostic recording system to aid the diagnosis of any physiological
      changes that occurs. The system comprises a central device, with a display screen, battery
      pack and memory card. The electrophysiological monitoring device will consists or three
      electrodes and wires which feeds into the central device ports. The electrodes will be
      attached to the participants' forehead; left central and right. The intra-abdominal pressure
      device consists of a transducer which is located in the urinary catheter. The wires which are
      connected to the transducers are then fed into the central device ports. The continuous
      estimated cardiac output monitoring devices consist of three cardiac electrodes, pulse
      oximetry device and wires, which are connected to the central device ports. The cardiac
      electrodes are placed to the participants' thorax and the pulse oximetry device is attached
      to the participants' digit either in the foot or hand.

      The following sensors will be applied:

        -  Electrocardiogram: recording cardiac electrical activity to give three recorded and
           three derived traces

        -  Ventilator: recording airflow inhale and exhalation, flow rate, pressure, tidal volume,
           peep, type of ventilator mode.

        -  Pulse oximeter: recording arterial oxygen saturation and pulse rate The monitoring
           system will be applied to the participant once assent is obtained and after the initial
           management; drug administration, examination and other investigation are performed by
           the clinical team. The sensors will be applied with the goal of recording continuously
           for seventy two hours.

      Intermittent monitoring Participant will undergo indirect calorimetry monitoring and LIMON
      test. Resting metabolic rate will be measured every 12 hourly for 72 hours using indirect
      calorimetry with Quark Resting Metabolic Rate (QUARK RMR) (COSMED, Rome, Italy). This device
      consist of canopy, ventilator tubing, heat and moisture exchange filter, air sample analyzing
      tubes, computer, gas analyzing chamber, calibration gas cylinder, air pump to calibrate the
      flow sensor, fuel cell, spirometry and Windows 8.0 computer which has COSMED Quark RMR
      software installed.

      Participants are either ventilated or awake. Ventilated participants will have a gas
      analyzing tubing attached to the heat and moisture exchange filter which is fed unto the gas
      analyzing chamber. The flow meter is attached at the exhaust port at the back of the
      ventilator.

      The measurement is taken until a steady resting state is achieved. This will normally vary
      from two minutes to 20 minutes. The results are automatically recorded onto the Quark RMR
      software. In order to achieve steady ventilation with little minimum bias flow the
      participants' Bispectral index is maintained between forty and sixty using medications such
      as propofol, fentanyl, midazolam or clonidine.

      Liver and splanchnic circulation will be measured every 6 hourly using LIMON Liver Function
      Monitor (Liver Monitor, PULSION Medical Systems, Munich, Germany) The device consist of
      sensor, wires and monitor to display the instructions and results. The sensor is attached to
      the participants' earlobe, finger tips in the hand or foot. The indocyanine green dye (ICG)
      is injected into a vein. The results will be displayed onto the monitor.

      If the recording is suboptimal due to loss of sensors or insufficient recording, it will be
      repeated.

      All of the above equipments and monitoring system will be cleaned and disinfected according
      to the manufacturing advice and microbiology team. The standard operating procedures for the
      above equipments are described in the appendix.

      Cessation of monitoring The recording system, or individual sensors will be removed
      immediately if it is required for clinical investigations or interventions. However, it is
      anticipated that most investigations and interventions will be able to proceed with the
      sensors in place. The device is expected to remain in place during patient re-positioning,
      airway management, delivery of oxygen, delivery of oral and IV medication and fluids and most
      imaging with the exception of magnetic resonance imaging.

      BIS monitoring will be removed in the event of cardio-respiratory arrest. If study clinician
      is not present at the time of cardio-respiratory arrest, the monitor will detach without
      difficulty and will not impede or delay resuscitation efforts.

      Date collection:

      In addition to above data, the investigator be collecting the patients' demographics
      including apache II scoring, end organ function including liver function, renal function,
      haematological status, ventilator settings, arterial gas, urine output and temperature.

      9. Data Analysis Analysis of recording Data will be exported from the monitoring devices
      after each recording and assessed for adequacy and quality.

      All frontal lobe electroencephalogram will be analysed. If there is any EEG finding that are
      consist with seizures it will be reviewed by neurophysiologist. All resting metabolic rate
      will be plotted against the physiological parameters including splanchnic circulation,
      temperature and intra-abdominal pressure. The ECG will be reviewed to assess heart rate,
      rhythm and conduction. Invasive blood pressure monitoring device will assess the blood
      pressure. Estimated cardiac output monitoring will assess the cardiac output and the trend
      over the seventy two hours. Fick principle will be used to calculate the cardiac output using
      the data (CaO2 and CVO2) obtained from the Quark RMR.

      Any stimulus, airway management, changes in the levels of sedation, return from theatres will
      be noted.

        1. Statistical Consideration In the view of the complexity of data provided by continuous
           monitoring, statistical guidance will be sought at all stages of analysis from the
           "Statistician. For the primary end points, the investigator will draw a graph of time
           again resting metabolic rate. The precise choice of test will be determined once the
           distribution pattern of the data is known. Repeated measure analysis of variance will be
           used followed by regression analysis accounted for repeat measures.

           In comparing patient specific outcome measures (mortality, requirement for ventilation,
           development of complications such as sepsis), participants will be placed into ranked
           groups from most to least difference in trend change in resting metabolic rate and
           nonparametric analysis will be used to assess the relationship between mortality or
           morbidity and resting metabolic rate.

        2. Sample Size Justification Primary determinant is expected number of eligible patients
           presenting in the duration of study.

      Power calculation was completed for the primary outcome measures. In order to conclude to
      show that there is an increase in metabolic rate by 200 kcal per day with a power of 0.8, I
      will need 8 patients to be able to conclude that there increase in metabolic rate.
observational model: Cohort
time perspective: Prospective
measure: Monitor the change in resting metabolic rate over period of time after severe burns injury.
time frame: Continuous monitoring over 72 hours
description: The resting metabolic rate will be measured using Quark Indirect Calorimetry Machine from Cosmed, Italy. The rested metabolic rate will be measured in kilo calories.
measure: Monitor the cardiac output using Fick principle in severe burns
time frame: The cardiac output will be measured using the fick principle.The cardiac output will be measured at 12th, 24th, 36th, 48th, 60th 72nd hour from the point of the injury. 10 patients will be recruited over a year.
description: The cardiac output will be measured in mls.
measure: Monitor the splanchnic circulation by measuring the indocyanine green clearance rate.
time frame: The splanchnic circulation will be measured at 12th, 24th, 36th, 48th, 60th 72nd hour from the point of the injury. 10 patients will be recruited over a year.
description: splanchnic circulation will be measured by using Limon machine from Maquet. The plasma clearance rate of indocyanine green will be measured in % per ml.
intervention type: Other
intervention name: observational study
description: No intervention
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Marcela Vizcaychipi
role: Principal Investigator
affiliation: Chelsea and Westminster NHS trust
last name: Asako Shida
phone: 07957497542
email: ashida@imperial.ac.uk
last name: Marcela Vizcaychipi
phone: 02087468903
email: m.vizcaychipi@imperial.ac.uk
facility: 
status: Recruiting
country: United Kingdom
citation: Herndon DN, Hart DW, Wolf SE, Chinkes DL, Wolfe RR. Reversal of catabolism by beta-blockade after severe burns. N Engl J Med. 2001 Oct 25;345(17):1223-9. doi: 10.1056/NEJMoa010342.
PMID: 11680441
citation: Huang YS, Yang ZC, Liu XS, Chen FM, He BB, Li A, Crowther RS. Serial experimental and clinical studies on the pathogenesis of multiple organ dysfunction syndrome (MODS) in severe burns. Burns. 1998 Dec;24(8):706-16. doi: 10.1016/s0305-4179(98)00123-5.
PMID: 9915670
citation: Jeschke MG, Gauglitz GG, Kulp GA, Finnerty CC, Williams FN, Kraft R, Suman OE, Mlcak RP, Herndon DN. Long-term persistance of the pathophysiologic response to severe burn injury. PLoS One. 2011;6(7):e21245. doi: 10.1371/journal.pone.0021245. Epub 2011 Jul 18.
PMID: 21789167
citation: Jeschke MG, Herndon DN, Wolf SE, DebRoy MA, Rai J, Lichtenbelt BJ, Barrow RE. Recombinant human growth hormone alters acute phase reactant proteins, cytokine expression, and liver morphology in burned rats. J Surg Res. 1999 May 15;83(2):122-9. doi: 10.1006/jsre.1999.5577.
PMID: 10329105
citation: Kasten KR, Makley AT, Kagan RJ. Update on the critical care management of severe burns. J Intensive Care Med. 2011 Jul-Aug;26(4):223-36. doi: 10.1177/0885066610390869.
PMID: 21764766
citation: CUTHBERTSON DP. Interrelationship of metabolic changes consequent to injury. Br Med Bull. 1954;10(1):33-7. doi: 10.1093/oxfordjournals.bmb.a069369. No abstract available.
PMID: 13126521
citation: CUTHBERTSON DP. Nutrition. Annu Rev Med. 1953;4:135-62. doi: 10.1146/annurev.me.04.020153.001031. No abstract available.
PMID: 13105270
citation: Bell JR, Clark AM, Cuthbertson DP. Experimental traumatic shock. J Physiol. 1938 May 14;92(4):361-70. doi: 10.1113/jphysiol.1938.sp003608. No abstract available.
PMID: 16994980
citation: Cathcart EP, Cuthbertson DP. The composition and distribution of the fatty substances of the human subject. J Physiol. 1931 Jul 6;72(3):349-60. doi: 10.1113/jphysiol.1931.sp002779. No abstract available.
PMID: 16994214
responsible party type: Principal Investigator
investigator affiliation: Chelsea and Westminster NHS Foundation Trust
investigator full name: Marcela P. Vizcaychipi
investigator title: Consultant in Anaesthesia and Intensive Care Medicine Honorary Senior Clinical Lecturer Divisional Research Lead for Planned Care Surgery and Clinical Support
mesh term: Burns
sharing ipd: No
ipd description: no, we do not plan to share participant data with other researchers.