The Effect of Combined Oral and Topical Analgesics to Reduce Pain Perception During Electrodiagnostic Testing
Condition: Pain Perception
Study type: Interventional

Summary: 
      Electromyography (EMG) is a useful test for diagnosis and monitoring of lower motor neuron
      disorders. It is mostly done in conjunction with a Nerve Conduction Study (NCS). Like other
      invasive medical procedures; electrodiagnostic tests have been known to cause iatrogenic pain
      for the patient, the intensity of which varies from person to person. Multiple modifiable as
      well as non-modifiable risk factors associated with EMG pain have been described in
      literature.Various approaches targeting different mechanisms of pain perception have been
      tested to make this procedure comfortable for the patients. These approaches range from
      simple distraction techniques to the use of topical and oral analgesics.Most of these studies
      have looked at adult population which has, supposedly, better pain tolerance as compared to
      children. Data on EMG associated pain in pediatric population is scant. This trial will
      assess the effect of combined oral and topical analgesics to reduce pain perception during
      NCS and EMG tests in the pediatric population.
    

Detailed description: 
      Objectives:

      To determine the effect of combined oral and topical analgesics (COTA) in reducing pain
      perception during NCS and EMG tests among the pediatric population.

      To compare the effect of COTA and only oral analgesics (OA) in reducing pain perception
      during NCS and EMG tests among the pediatric population.

      Methods:

      Study Setting: This study will be conducted at the neurophysiology lab at Aga Khan University
      Hospital (AKUH)

      Study Design: This will be a stratified (6 months - 6 years and 7 - 18 years with balanced
      randomization), double-blind, placebo-controlled, parallel group study conducted at the
      neurophysiology lab, AKUH.

      Variables:

      Independent Variables - Gender, age, weight (Kg), number of muscles sampled, distribution of
      muscles sampled, end plate noise detection, type of needle used, duration of EMG and NCS
      test, history of undergoing electrodiagnostic tests in the past, time duration between
      analgesic intake / application and start of the NCS and EMG test, number of needle insertions
      needed outside of applied cream area, number of times skin is pierced,result of
      electrodiagnostic examination, patient in parents lap, electromyographer, study arm.

      Dependent Variables - Pain Scores (MBPS and FPS-R)

      Interventions/Study Protocol:

      The guardians / patients who meet the inclusion criteria, as determined by the
      neurophysiology fellow or attending, will be instructed to reach the neurophysiology lab on
      the day of appointment one hour before the expected procedure time. All patients and/or their
      guardians referred for NCS / EMG will be given a standard explanation regarding the procedure
      and study details on the day of electrodiagnostic testing by the designated neurophysiology
      technologist. NCS would be explained as a test that checks the responses of the nerves and
      the subject will feel small zaps during the procedure. EMG would be explained as a procedure
      where a thin small microphone will be inserted in multiple muscles of the arm, leg and / or
      neck and back that will help us in identifying the problem. The word 'needle' and 'electric
      current' would not be used during this explanation. The guardian and patient, if old enough
      to understand, will also be explained the study protocol being carried out. Written Informed
      consent for the procedure itself and the study will be taken at this point by the
      neurophysiology fellow. Patients (older than 6 years) or their guardians will be instructed
      on how to administer the FPS-R scale. In addition guardians would be instructed to make sure
      that patients are not given sugary drinks or breastfeed during 1 hour prior to the procedure.
      During the study distractions will be kept to a minimum and similar for all patients. Sites
      of needle insertion will not be rubbed, stroked or tapped at the time of needle insertion.
      These factors are known confounders in reducing intramuscular injection pain. Those who have
      given consent will be assigned to one of the three arms of the study according to the
      randomization schedule; COTA arm (Ibuprofen Syrup and EMLA Cream), OA arm (Ibuprofen Syrup
      and Plain Cream) or Placebo arm (Plain Syrup and Plain Cream). All patients will be issued
      their interventions labeled with an allocation sequence according to the randomization
      schedule from the clinical trials unit (CTU), in a double blind manner, on the day of
      appointment. The syrup will be given to patients orally (10mg/Kg body weight) at least 1 hour
      prior to start of procedure. The electromyographer will demarcate all the possible muscle
      sampling sites required as per study protocol with a non-toxic marker and leave the room. A
      neurophysiology technologist will apply the cream on all demarcated sites. After application
      of cream, the site would be covered by an occlusive dressing until NCS / EMG is carried out
      so as to keep the applied cream in place and prevent accidental ingestion or application on
      mucosal surfaces by the patient. The patient will be kept under observation for adverse
      reactions including blanching and local erythema from application of cream till 15 minutes
      after the NCS / EMG procedure. Observation would be done by Neurophysiology fellow or the
      Neurophysiology attending. Neurophysiology technologists designated to carry out this
      exercise would be given combined sessions regarding the application technique to achieve
      consistency in results.

      The EMG will be performed by board certified faculty or neurophysiology fellows under their
      supervision, each of them having a minimum of 6 months experience in doing electrodiagnostic
      testing. This involves intramuscular insertion of needle (that has a microphone at its tip)
      into multiple muscles. The occlusive dressing will be removed and area to be tested wiped
      with alcohol swabs. Nerve conduction studies will be conducted first followed by the needle
      procedures. During nerve conduction studies, patients feel an electric current like sensation
      whenever a nerve is tested. Attempt will be made to keep the needle movements to minimum. The
      guardian would accompany the child throughout the procedure. If the child wants, he/she would
      be allowed to sit in the guardians lap during the procedure.

      Pain Assessment & Data Collection:

      For children aged 6 months to 6 years pain will be assessed by scoring facial expression, cry
      and body movements of the children using the Modified Behavioral Pain Scale (MBPS). For
      children aged 7 years to 18 years the Face Pain Scale-Revised (FPS-R) version will be used.
      Patients will be scored before NCS, after NCS and after EMG respectively on the data
      collection form. Two observers blinded to the rest of the study and not involved with
      carrying out NCS / EMG will be trained to administer these scores. The guardian, who would be
      unaware of what the child scored, will also be shown the FPS-R and asked to score how much
      pain patient seemed to feel during NCS and EMG respectively. Regarding FPS-R, the instruction
      will be to choose the face that most closely resembles the amount of pain being felt. Patient
      demographics, Clinical characteristics and NCS / EMG procedure characteristics will also be
      recorded on the form. The data collected will then be entered into an excel sheet at the end
      of each day.

      Sample Size:

      Assuming a difference in means of 1.4 with a standard deviation of 1.73 in the control group
      and 2.17 in the intervention group on the MBPS according to a study assessing effectiveness
      of EMLA cream for reducing pain during Intramuscular injections in the pediatric population,
      an alpha level of 0.05 and power of 80 % using a 1-way analysis of variance (ANOVA) test with
      3 pairwise comparisons; we will require 35 patients per group. Furthermore, assuming a 10 %
      dropout rate we will enroll 39 patients per group to account for it.

      Randomization:

      To achieve comparable groups, randomization will be performed as stratified blocked
      randomization with random sizes in a 1:1 allocation ratio. Stratification will be done
      according to the age groups: 6 months - 6 years and 7 - 18 years with varying random block
      sizes. Allocation to intervention groups according to stratification will be carried out by a
      computer generated randomization schedule which will list the allocation sequences assigned
      to each of the three arms. The randomization schedule will only be available with the
      pharmacist in charge of preparing interventions. Interventions will be prepared in
      indistinguishable containers containing plain cream and EMLA cream and bottles containing
      plain syrup and Ibuprofen syrup. The creams will be prepared to be similar in consistency,
      texture and color. The syrups will also be similar in color and taste. Thirty Nine
      Intervention packages will be made for each of the intervention arms; COTA arm, OA arm and
      Placebo arm. Each intervention will be labelled with an allocation sequence according to the
      randomization schedule by the pharmacist. The independent study officer not involved with the
      preparation or packaging of interventions and blinded to the rest of the study will issue the
      intervention for each patient reporting on the day of the appointment. The random allocation
      sequence would be concealed from the rest of the study investigators / researchers.

      Blinding:

      Throughout the study the patients, the electromyographers, neurophysiology technologists /
      observers administering the validated pain scales will be unaware of the intervention
      assignments.

      Safety Management:

      The drugs used in intervention arm have FDA approval as analgesics in the study population.
      Moreover, no prior testing is recommended before administration of these over the counter
      analgesics. Our study involves a single time use of these drugs only. Possible side effects
      (1-10%) with Ibuprofen include dizziness, epigastric pain, heart burn, nausea, rash, vomiting
      and renal failure (<1%). Possible side effects (>10%) with EMLA application include
      application site pallor/blanching, erythema/pain and application site oedema (1-10%),
      itching. Rare adverse effects (<1%) include methemoglobinemia and myocardial dysfunction.
      Patients will be observed for 15 minutes post study for the development of any side effects.
      If any side effect is observed, patients would be referred to consult respective speciality
      as deemed appropriate, as per the severity of adverse event. The patient or his/her guardian
      will bear the expenses. This would be mentioned at the time of taking informed consent.

      Data Handling & Storage:

      All patient related data would be kept safe in the custody of designated study officer who
      would be part of the neurophysiology lab. Informed consent forms would be signed in a
      separate room.

      Statistical Analysis:

      Data will be assessed for normality. We will use descriptive statistics for patient
      demographics, clinical characteristics and NCS / EMG test characteristics, including measures
      of central tendency and dispersion. Comparisons between three groups on pain perception will
      be performed using ANOVA. Differences in proportions will be assessed using chi-square test
      or Fischer exact test where appropriate. Logistic and Linear regression models will be used
      to assess the effect of patient demographics, clinical characteristics and NCS / EMG test
      characteristics on patient pain reduction within and across intervention groups. All p-values
      will be two sided and considered as statistically significant if < 0.05. All analyses will be
      conducted by using the Statistical package for social science SPSS (Release 19.0, standard
      version, copyright © SPSS; 1989-02).
    

Intervention name(s): EMLA Cream; Ibuprofen; Placebo syrup; Placebo cream
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Topical anaesthetic cream; Oral analgesic syrup (non-steroidal anti inflammatory drug); Placebo syrup similar to Ibuprofen; Placebo cream similar to EMLA
Intervention MeSH terms: Ibuprofen; Lidocaine, Prilocaine Drug Combination
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double blind placebo controlled randamized controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Electromyopharpy; Nerve conduction study; Electrodiagnostic testing; Edx study; EMG; NCS