<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/NCT01706354</url>
  </required_header>
  <id_info>
    <org_study_id>12/WS/0199</org_study_id>
    <nct_id>NCT01706354</nct_id>
  </id_info>
  <brief_title>Local Anaesthesia vs Regional Block for Arteriovenous Fistulae</brief_title>
  <official_title>Does Regional Compared to Local Anaesthesia Influence Outcome After Arteriovenous Fistula Creation?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emma Aitken</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NHS Greater Glasgow and Clyde</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>NHS Greater Glasgow and Clyde</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      End stage renal failure (ESRF)describes an irreversible loss in renal function. The majority&#xD;
      of these patients will opt for haemodialysis (HD)as their chosen method of renal replacement&#xD;
      therapy (RRT). Arteriovenous fistulae (AVF) are the optimal method of achieving vascular&#xD;
      access to permit HD. AVF are created with a small surgical procdure to join the artery and&#xD;
      vein together. Over the next 6- 8weeks after surgery the AVF should grow (&quot;mature&quot;) into a&#xD;
      vessel suitable for needles to be inserted for dialysis. Unfortunately however, around 24% -&#xD;
      35% of AVF fail at an early stage. Some anaesthetic techniques can influence intraoperative&#xD;
      blood flow and venous diameter, factors which are associated with fistula success. There&#xD;
      remains no conclusive evidence that any particular anaesthetic technique can significantly&#xD;
      influence long term surgical outcome. This study aims to investigate whether a regional,&#xD;
      compared to local, anaesthetic technique can affect fistula patency.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic kidney disease (CKD) describes abnormal kidney structure or function and is a&#xD;
      significant public health problem. It is common, increasingly prevalent with age and often&#xD;
      co-exists with significant morbidities, such as diabetes mellitus, hypertension,&#xD;
      hyperlipidaemia, cerebrovascular disease and coronary artery disease. Patients with a&#xD;
      diagnosis of CKD have a decreased life expectancy compared with individuals without this&#xD;
      diagnosis. This is primarily due to cardiovascular disease, but other complications of CKD&#xD;
      include bone and mineral disorders, anaemia, depression, and malnutrition. Early recognition&#xD;
      and treatment of these complications is recommended.&#xD;
&#xD;
      In a proportion of patients, CKD will progress to end stage renal disease (ESRD). This is&#xD;
      defined as an irreversible decline in kidney function for which renal replacement therapy&#xD;
      (RRT) is required if the patient is to survive. In one UK study, 4% of patients with CKD&#xD;
      progressed to develop ESRD requiring RRT over a five and a half year follow up period. The&#xD;
      decision to commence RRT takes into account symptoms of biochemical disturbance, in&#xD;
      conjunction with the risks and inconvenience of starting RRT. European Best Practice&#xD;
      Guidelines recommend that RRT should commence when the estimated Glomerular Filtration Rate&#xD;
      (eGFR) falls below 15ml/min/1.73m2 or when symptoms of uraemia, fluid overload or&#xD;
      malnutrition are resistant to medical therapy. In an asymptomatic patient, an eGFR of below&#xD;
      6ml/min/1.73m2 would also prompt the initiation of dialysis. It is known that the life&#xD;
      expectancy of patients receiving RRT is shorter than that of the general population and&#xD;
      varies further dependent on underlying diagnosis and age. For example, the median survival&#xD;
      for a patient in Scotland aged 45 - 64 years starting RRT for glomerulonephritis is 7.7&#xD;
      years, whereas the median survival of a patient in the same age group with a diagnosis of&#xD;
      diabetic nephropathy is 2.9 years. The life expectancy of a male of the same age group within&#xD;
      the general Scottish population is 24.2 years. Instituting RRT prolongs life and reduces the&#xD;
      incidence of vasculo-occlusive events in patients with ESRD. As such, patients with CKD&#xD;
      should be monitored by a nephrologist in order that timely referral for preparation for RRT&#xD;
      can be made.&#xD;
&#xD;
      Renal replacement therapy may come in the form of haemodialysis, peritoneal dialysis or renal&#xD;
      transplantation, and may be managed both in and out of hospital. Haemodialysis (HD) remains&#xD;
      the most common modality of first RRT in Scotland; of 2885 patients commencing RRT during the&#xD;
      period 2005-2009, 2264 received HD. In order to undergo HD, there must be a connection&#xD;
      between the patient's vascular system and the dialysis machine. The most common method is&#xD;
      surgical creation of an arteriovenous fistula (AVF), into which a needle can be inserted that&#xD;
      in turn is connected to a dialysis machine. In 2009, 75% of Scottish patients undergoing HD&#xD;
      underwent formation of an arteriovenous fistula (AVF). Other options for vascular access&#xD;
      include arteriovenous grafts using synthetic materials and long-term central venous&#xD;
      catheters, though these are associated with higher rates of occlusive and infective&#xD;
      complications. AVF are currently regarded as the optimal form of vascular access for HD and&#xD;
      are recommended by National guidelines. There is excellent evidence that good quality, stable&#xD;
      vascular access is a major factor in determining survival in this group of CKD patients.&#xD;
      Unfortunately however, around 24% - 35% of arteriovenous fistulae (AVF) fail at an early&#xD;
      stage. Some anaesthetic techniques can influence intraoperative blood flow and venous&#xD;
      diameter, factors which are associated with fistula success. There remains no conclusive&#xD;
      evidence that any particular anaesthetic technique can significantly influence long term&#xD;
      surgical outcome. This study aims to investigate whether a regional, compared to local,&#xD;
      anaesthetic technique can affect fistula patency.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2012</start_date>
  <completion_date type="Anticipated">October 2015</completion_date>
  <primary_completion_date type="Anticipated">October 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary patency</measure>
    <time_frame>3 months</time_frame>
    <description>Primary patency defined as unequivocal maturation to permit cannulation with thrill and bruit without intervention (Y/N)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immediate Patency</measure>
    <time_frame>1 hours post-operatively</time_frame>
    <description>Defined as the unequivocal presence of thrill and bruit in the fistula in recovery room 1 hour post-opertaively (Y/N)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary patency</measure>
    <time_frame>1 month, 1year</time_frame>
    <description>Defined as the unequivoval presence of a thrill/ bruit at 1 month/ 1 year (Y/N)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional patency</measure>
    <time_frame>1, 3 and 12 months</time_frame>
    <description>Defined as a fistula capable of sustaining two needles haemodialysis for at least 6 consecutive sessions without intervention(Y/N)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary patency</measure>
    <time_frame>3 and 12 months</time_frame>
    <description>Defined as a fistula suitable to sustain haemodialysis only after additional intervention (e.g. revisional surgery/ angioplasty)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ultrasound flows in brachial artery</measure>
    <time_frame>Pre-/post anaesthetic, 1, 3 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Success of anaesthetic</measure>
    <time_frame>Immediate</time_frame>
    <description>Complications and efficacy (VAS for pain)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">126</enrollment>
  <condition>End Stage Renal Disease</condition>
  <arm_group>
    <arm_group_label>Local anaesthetic</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Infiltration of local anaesthetic into the surgical site by the surgeon using a combination of 0.5% L-bupivicaine prior to incision and 1% lignocaine topically after the wound is opened. Maximum dose limits of 2mg/kg for bupivicaine, and 3mg/kg for lignocaine will be observed, recognising that these are additive.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regional anaesthetic</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ultrasound guided brachial plexus block. Supraclavicular will be the block performed unless there is a contraindication in which case axillary block may be used. A 1:1 mixture of 0.5% L-bupivicaine and 1.5% lignocaine with adrenaline (1 in 200,000) will be injected, up to a volume of 40ml but using a minimum of 25ml. Maximum dose limits of 2mg for bupivicaine and 7mg/kg for lignocaine with adrenaline will be observed, recognising that these are additive.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Local Anaesthetic</intervention_name>
    <description>Infiltration of local anaesthetic into the surgical site by the surgeon using a combination of 0.5% L-bupivicaine prior to incision and 1% lignocaine topically after the wound is opened. Maximum dose limits of 2mg/kg for bupivicaine, and 3mg/kg for lignocaine will be observed, recognising that these are additive.</description>
    <arm_group_label>Local anaesthetic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Regional anaesthetic</intervention_name>
    <description>Ultrasound guided brachial plexus block. Supraclavicular will be the block performed unless there is a contraindication in which case axillary block may be used. A 1:1 mixture of 0.5% L-bupivicaine and 1.5% lignocaine with adrenaline (1 in 200,000) will be injected, up to a volume of 40ml but using a minimum of 25ml. Maximum dose limits of 2mg for bupivicaine and 7mg/kg for lignocaine with adrenaline will be observed, recognising that these are additive.</description>
    <arm_group_label>Regional anaesthetic</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  English-speaking&#xD;
&#xD;
          -  Adult patients &gt;18 years old&#xD;
&#xD;
          -  Competent to give consent&#xD;
&#xD;
          -  Scheduled for primary AVF formation at either radial or brachial artery.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy to local anaesthetic.&#xD;
&#xD;
          -  Coagulopathy&#xD;
&#xD;
          -  Infection at the anaesthetic or surgical site.&#xD;
&#xD;
          -  Patient preference for general or alternative anaesthesia&#xD;
&#xD;
          -  Significant peripheral neuropathy or neurologic disorder affecting the upper extremity&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Previous AVF creation&#xD;
&#xD;
          -  Known cephalic vein occlusion, central vein stenosis, brachial or radial artery&#xD;
             stenosis&#xD;
&#xD;
          -  Vein or artery less than 1.8mm, as measured by ultrasound&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marc Clancy, MBBS FRCS</last_name>
    <role>Principal Investigator</role>
    <affiliation>NHS Greater Glasgow and Clyde</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marc Clancy, MBBS PhD</last_name>
    <phone>0141 211 1750</phone>
    <email>Marc.Clancy@ggc.scot.nhs.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Emma Aitken, MBChB MRCS</last_name>
    <phone>0141 211 1750</phone>
    <email>Emma.Aitken@nhs.net</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Renal Surgery, Western Infirmary</name>
      <address>
        <city>Glasgow</city>
        <zip>G116NY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marc Clancy, MBBS PhD FRCS</last_name>
      <phone>0141 211 1750</phone>
      <email>Marc.Clancy@ggc.scot.nhs.uk</email>
    </contact>
    <contact_backup>
      <last_name>Emma Aitken, MBChB MRCS</last_name>
      <phone>0141 211 1750</phone>
      <email>EmmaAitken@nhs.net</email>
    </contact_backup>
    <investigator>
      <last_name>Marc Clancy, MBBS FRCS</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alan McFarlane, MBChB FRCA</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rachel Kearns, MBChB FRCA</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Emma Aitken, MBChB MRCS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 3, 2012</study_first_submitted>
  <study_first_submitted_qc>October 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2012</study_first_posted>
  <last_update_submitted>October 11, 2012</last_update_submitted>
  <last_update_submitted_qc>October 11, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 15, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>NHS Greater Glasgow and Clyde</investigator_affiliation>
    <investigator_full_name>Emma Aitken</investigator_full_name>
    <investigator_title>Clinical Research Fellow Department of Renal Surgery</investigator_title>
  </responsible_party>
  <keyword>end stage renal disease</keyword>
  <keyword>vascular access</keyword>
  <keyword>regional anaesthesia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Kidney Failure, Chronic</mesh_term>
    <mesh_term>Arteriovenous Fistula</mesh_term>
    <mesh_term>Fistula</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anesthetics</mesh_term>
    <mesh_term>Anesthetics, Local</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/NCT01706354
org study id: 12/WS/0199
nct id: NCT01706354
lead sponsor: 
collaborator: 
has dmc: No
End stage renal failure (ESRF)describes an irreversible loss in renal function. The majority
      of these patients will opt for haemodialysis (HD)as their chosen method of renal replacement
      therapy (RRT). Arteriovenous fistulae (AVF) are the optimal method of achieving vascular
      access to permit HD. AVF are created with a small surgical procdure to join the artery and
      vein together. Over the next 6- 8weeks after surgery the AVF should grow ("mature") into a
      vessel suitable for needles to be inserted for dialysis. Unfortunately however, around 24% -
      35% of AVF fail at an early stage. Some anaesthetic techniques can influence intraoperative
      blood flow and venous diameter, factors which are associated with fistula success. There
      remains no conclusive evidence that any particular anaesthetic technique can significantly
      influence long term surgical outcome. This study aims to investigate whether a regional,
      compared to local, anaesthetic technique can affect fistula patency.
Chronic kidney disease (CKD) describes abnormal kidney structure or function and is a
      significant public health problem. It is common, increasingly prevalent with age and often
      co-exists with significant morbidities, such as diabetes mellitus, hypertension,
      hyperlipidaemia, cerebrovascular disease and coronary artery disease. Patients with a
      diagnosis of CKD have a decreased life expectancy compared with individuals without this
      diagnosis. This is primarily due to cardiovascular disease, but other complications of CKD
      include bone and mineral disorders, anaemia, depression, and malnutrition. Early recognition
      and treatment of these complications is recommended.

      In a proportion of patients, CKD will progress to end stage renal disease (ESRD). This is
      defined as an irreversible decline in kidney function for which renal replacement therapy
      (RRT) is required if the patient is to survive. In one UK study, 4% of patients with CKD
      progressed to develop ESRD requiring RRT over a five and a half year follow up period. The
      decision to commence RRT takes into account symptoms of biochemical disturbance, in
      conjunction with the risks and inconvenience of starting RRT. European Best Practice
      Guidelines recommend that RRT should commence when the estimated Glomerular Filtration Rate
      (eGFR) falls below 15ml/min/1.73m2 or when symptoms of uraemia, fluid overload or
      malnutrition are resistant to medical therapy. In an asymptomatic patient, an eGFR of below
      6ml/min/1.73m2 would also prompt the initiation of dialysis. It is known that the life
      expectancy of patients receiving RRT is shorter than that of the general population and
      varies further dependent on underlying diagnosis and age. For example, the median survival
      for a patient in Scotland aged 45 - 64 years starting RRT for glomerulonephritis is 7.7
      years, whereas the median survival of a patient in the same age group with a diagnosis of
      diabetic nephropathy is 2.9 years. The life expectancy of a male of the same age group within
      the general Scottish population is 24.2 years. Instituting RRT prolongs life and reduces the
      incidence of vasculo-occlusive events in patients with ESRD. As such, patients with CKD
      should be monitored by a nephrologist in order that timely referral for preparation for RRT
      can be made.

      Renal replacement therapy may come in the form of haemodialysis, peritoneal dialysis or renal
      transplantation, and may be managed both in and out of hospital. Haemodialysis (HD) remains
      the most common modality of first RRT in Scotland; of 2885 patients commencing RRT during the
      period 2005-2009, 2264 received HD. In order to undergo HD, there must be a connection
      between the patient's vascular system and the dialysis machine. The most common method is
      surgical creation of an arteriovenous fistula (AVF), into which a needle can be inserted that
      in turn is connected to a dialysis machine. In 2009, 75% of Scottish patients undergoing HD
      underwent formation of an arteriovenous fistula (AVF). Other options for vascular access
      include arteriovenous grafts using synthetic materials and long-term central venous
      catheters, though these are associated with higher rates of occlusive and infective
      complications. AVF are currently regarded as the optimal form of vascular access for HD and
      are recommended by National guidelines. There is excellent evidence that good quality, stable
      vascular access is a major factor in determining survival in this group of CKD patients.
      Unfortunately however, around 24% - 35% of arteriovenous fistulae (AVF) fail at an early
      stage. Some anaesthetic techniques can influence intraoperative blood flow and venous
      diameter, factors which are associated with fistula success. There remains no conclusive
      evidence that any particular anaesthetic technique can significantly influence long term
      surgical outcome. This study aims to investigate whether a regional, compared to local,
      anaesthetic technique can affect fistula patency.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: Primary patency
time frame: 3 months
description: Primary patency defined as unequivocal maturation to permit cannulation with thrill and bruit without intervention (Y/N)
measure: Immediate Patency
time frame: 1 hours post-operatively
description: Defined as the unequivocal presence of thrill and bruit in the fistula in recovery room 1 hour post-opertaively (Y/N)
measure: Primary patency
time frame: 1 month, 1year
description: Defined as the unequivoval presence of a thrill/ bruit at 1 month/ 1 year (Y/N)
measure: Functional patency
time frame: 1, 3 and 12 months
description: Defined as a fistula capable of sustaining two needles haemodialysis for at least 6 consecutive sessions without intervention(Y/N)
measure: Secondary patency
time frame: 3 and 12 months
description: Defined as a fistula suitable to sustain haemodialysis only after additional intervention (e.g. revisional surgery/ angioplasty)
measure: Ultrasound flows in brachial artery
time frame: Pre-/post anaesthetic, 1, 3 and 12 months
measure: Patient satisfaction
time frame: 24 hours
measure: Success of anaesthetic
time frame: Immediate
description: Complications and efficacy (VAS for pain)
arm group label: Local anaesthetic
arm group type: Active Comparator
description: Infiltration of local anaesthetic into the surgical site by the surgeon using a combination of 0.5% L-bupivicaine prior to incision and 1% lignocaine topically after the wound is opened. Maximum dose limits of 2mg/kg for bupivicaine, and 3mg/kg for lignocaine will be observed, recognising that these are additive.
arm group label: Regional anaesthetic
arm group type: Experimental
description: Ultrasound guided brachial plexus block. Supraclavicular will be the block performed unless there is a contraindication in which case axillary block may be used. A 1:1 mixture of 0.5% L-bupivicaine and 1.5% lignocaine with adrenaline (1 in 200,000) will be injected, up to a volume of 40ml but using a minimum of 25ml. Maximum dose limits of 2mg for bupivicaine and 7mg/kg for lignocaine with adrenaline will be observed, recognising that these are additive.
intervention type: Procedure
intervention name: Local Anaesthetic
description: Infiltration of local anaesthetic into the surgical site by the surgeon using a combination of 0.5% L-bupivicaine prior to incision and 1% lignocaine topically after the wound is opened. Maximum dose limits of 2mg/kg for bupivicaine, and 3mg/kg for lignocaine will be observed, recognising that these are additive.
arm group label: Local anaesthetic
intervention type: Procedure
intervention name: Regional anaesthetic
description: Ultrasound guided brachial plexus block. Supraclavicular will be the block performed unless there is a contraindication in which case axillary block may be used. A 1:1 mixture of 0.5% L-bupivicaine and 1.5% lignocaine with adrenaline (1 in 200,000) will be injected, up to a volume of 40ml but using a minimum of 25ml. Maximum dose limits of 2mg for bupivicaine and 7mg/kg for lignocaine with adrenaline will be observed, recognising that these are additive.
arm group label: Regional anaesthetic
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marc Clancy, MBBS FRCS
role: Principal Investigator
affiliation: NHS Greater Glasgow and Clyde
last name: Marc Clancy, MBBS PhD
phone: 0141 211 1750
email: Marc.Clancy@ggc.scot.nhs.uk
last name: Emma Aitken, MBChB MRCS
phone: 0141 211 1750
email: Emma.Aitken@nhs.net
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United Kingdom
responsible party type: Sponsor-Investigator
investigator affiliation: NHS Greater Glasgow and Clyde
investigator full name: Emma Aitken
investigator title: Clinical Research Fellow Department of Renal Surgery
mesh term: Kidney Diseases
mesh term: Kidney Failure, Chronic
mesh term: Arteriovenous Fistula
mesh term: Fistula
mesh term: Anesthetics
mesh term: Anesthetics, Local