Effect of Pretreatment of Lignocaine Versus Midazolam in Prevention of Etomidate Induced Myoclonus.
Condition: Myoclonic Jerk
MeSH terms: Myoclonus
Study type: Interventional
Phase: Phase 4

Summary: 
      This study is a randomized control trial and it was conducted to compare the effectiveness of
      pretreatment with lignocaine versus midazolam on the frequency of myoclonus associated with
      etomidate induction.

      This was conducted in Holy Family Hospital Rawalpindi in a period of 6 months.
    

Detailed description: 
      INTRODUCTION:

      General anaesthesia is loss of consciousness induced after administration of one or more
      general anaesthetic agent with overall aim of inducing sleep, amnesia, analgesia and skeletal
      muscles relaxation. Choosing an induction agent is a very vital step in commencing general
      anaesthesia1. Use of sedatives can prevent or minimize potentially harmful physiologic
      affects of airway manipulation that include increase in heart rate, BP, and raised
      intracranial pressure.

      Etomidate, imidazole-derived, sedative-hypnotic agent, blocks neuroexcitation by its direct
      action on the gamma amino butyric acid (GABA) receptor complex1.Because of its many desirable
      properties like rapid onset of action, profound hypnosis, minimal histamine release,
      hemodynamic stability, minimal respiratory depression, and favorable cerebral effects,
      etomidate is considered as an ideal induction agent2. Concerns with etomidate include adrenal
      suppression and myoclonus3, 4.

      30 to 60% of unpremedicated patients develop myoclonic movements after an induction dose (0.3
      mg/kg) of etomidate1. Myoclonus is described as the involuntary contraction of some muscle
      fibers, leading to short observable movements of the body, more pronounced with the limbs5.
      In emergency scenarios, myoclonus can lead to increment in the chances of regurgitation and
      aspiration.

      Various drugs like Lignocaine, Midazolam, Magnesium, Dezocine and dexmedetomidine have been
      used as pretreatment for reducing myoclonus after etomidate injection but the best drug for
      the purpose is yet to be discovered6, 7, 8, 9. Ideally a pretreatment drug should be
      short-acting, should affect respiration and hemodynamic minimally, and should not prolong the
      recovery period.

      Lignocaine belongs to amide group of local anaesthetics.Lignocaine alters signal conduction
      in neuronal cell membrane8. Various studies have been conducted on lignocaine being used as a
      pretreatment drug; before propofol induction to reduce pain or etomidate to prevent myoclonus
      associated with etomidateinduction6.

      Midazolam, a benzodiazepine, produce a calming effect on the brain and nerves 1, 10. Its
      various favorable effects include antiepileptic properties, anxiolysis, sedation, reduced
      attention and amnesia7. In a comparative study conducted by Singh KA (initials for first and
      second name of the author) et al, effect of pretreatment with lignocaine, midazolam and
      placebo were compared in prevention of etomidate induced myoclonus and the incidence was
      found to be 44%, 28% and 76% respectively5 (P<0.05). However, none of these studies have been
      conducted in Pakistan. The basic aim of my study is to compare the effectiveness of
      pretreatment with Lignocaine versus Midazolam on the frequency of myoclonus associated with
      etomidate induction, generate data regarding the effects, so that the more effective drug can
      be used routinely for the prevention of myoclonus associated with etomidate induction in
      routine.

      METHODOLOGY:

      After obtaining approval from the hospital ethics committee and written informed consent, 112
      patient were recruited according to selection criteria in each group. All patients were
      assessed a day before surgery for anaesthesia fitness. Patient were prepared by fasting (8 h
      for solid foods, 4 hours for clear fluids).Patient were randomly divided into two equal
      groups by computer-generated numbers.

      Group A received 1 ml of 2% lignocaine 2 min before induction with etomidate and Group B
      received 1 ml (1mg) of midazolam 2 min before induction with etomidate. On reaching the
      operating theater, standard monitoring were placed on all the participants, which included
      pulse oximeter, ECG and non-invasive blood pressure. A 20 G cannula with an intravenous line
      was maintained with 0.9% saline. Vitals such as pulse rate, blood pressure, respiratory rate,
      and oxygen saturation were recorded and taken as baseline readings. All patients were then
      preoxygenated with 100% oxygen for 3 min. Patients were divided randomly into two groups of
      112 using computer generated random numbers. Group I received 1 ml of 2% lignocaine, and
      group II received 1 ml of midazolam (1 mg). The test solutions were prepared in coded
      syringes and were administered 2 min before etomidate induction (0.3 mg/kg) by an observer
      who was blinded to the allocation of the groups as well as the drug given to him. The time to
      the loss of eyelash reflex was recorded as the onset of induction, and an additional dose of
      etomidate was administered if necessary. The patients were observed continuously for
      myoclonic movements. The time of onset and the duration of myoclonus was observed. One minute
      post IV injection of etomidate and the observation of myoclonus, 0.5 mg/kg succinylcholine
      was administered to allow endotracheal tube placement. The vitals were observed after
      administration of test solution, after induction, and after endotracheal intubation every
      minute for five minutes, then every five minutes for fifteen minutes, and then every fifteen
      minutes till the surgery ends. Anesthesia was maintained with isoflurane (0.5-1%) and
      atracurium.

      Data was collected on a standardized Proforma and analyze using SPSS-17 version (Statistical
      package for the social sciences). Mean ± SD (standard deviation) was calculated for
      quantitative variables lik age, weight and BMI. Qualitative variables like gender, myoclonus
      wer expressed as frequencies and percentages. Chi-square was used to compare th frequency of
      myoclonus in two groups. A P value less than 0.05 was consider statistically significant.
      Effect modifiers like age and gender were controlled b stratification. Post-stratification
      Chi-square test was applied.
    

Intervention name(s): lignocaine; Midazolam 1 milligram Prefilled Syringe
Intervention type(s): Drug; Drug
Intervention description(s): After giving lignocaine to a group of people, myoclonus was observed after the dose of etomidate given two minutes after lignocaine.; after giving midazolam to the second group of people two minutes before etomidate dose, myoclonus was observed for one minute.
Other intervention name(s): 2% lignocaine 1 ml; Dormicum
Intervention MeSH terms: Lidocaine; Midazolam
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: two arm parallel assignment, two groups, receive two different drugs ;drug A and drug B to see the effect.
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Prevention