The Effect of Magnesium Sulphate on the Time Course of Rocuronium Induced Neuromuscular Block
Condition: Neuromuscular Blockade
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of this study is to investigate whether an optimized pre-treatment with intravenous
      magnesium enhances the speed of onset of a standard intubation dose of rocuronium.
    

Detailed description: 
      In a previous study pre-treatment with intravenous MgSO4 60 mg kg-1 was not shown to have any
      impact on the onset of action of rocuronium [Kussmann et al, 1997]. Yet, in that study, MgSO4
      was injected as a bolus after induction of anaesthesia, one minute only before the injection
      of the neuromuscular blocking agent. We suppose that magnesium needs some time to penetrate
      the neuromuscular endplate and to shift the Mg/Ca ratio in favor of magnesium. Thus, the
      particular design of the previous study may explain why magnesium had no scope to enhance the
      speed of onset of action of rocuronium.

      The aim of our study is to investigate whether an optimised pre-treatment with magnesium
      (short infusion rather than bolus injection; reasonable delay between administration of
      magnesium and subsequent injection of the neuromuscular blocking agent) enhances the speed of
      onset of a standard intubation dose of rocuronium.

        1. Preanaesthetic preparation

             -  Solid food and liquid intake will not be allowed for a minimum of six hours before
                induction

             -  Patients will be premedicated with 7.5 mg oral midazolam 45 min prior to induction

             -  Standard monitoring will consist of: ECG, SaO2, ETCO2, non-invasive blood pressure,
                rectal or oesophageal T°

        2. Study drug administration

             -  Intravenous infusion of the study solution, 1 ml per kg bodyweight, corresponding
                to MgSO4 60 mg kg-1 in the magnesium group. The infusion will be given with an
                Infusomat during 15 minutes.

        3. Induction and maintenance of anaesthesia

             -  At the end of the study drug infusion, and after a preoxygenation period of three
                minutes, anaesthesia will be induced with sufentanil 0.2µg kg-1 and propofol, using
                a Target Controlled Infusion (TCI) system (Base Primea, Fresenius-Vial, Brezins,
                France) and the pharmacokinetic model of Schnider et al [Schnider et al, 1999]. The
                initial effect site concentration will be 4 µg ml-1.

             -  Maintenance of anaesthesia will be with a propofol effect site

        4. Neuromuscular monitoring

             -  Neuromuscular function will be monitored using the TOF Watch® SX (NV Organon) and
                TOF nerve stimulation. The guidelines for good clinical research practice in
                pharmacodynamic studies of NMBAs will be followed.

             -  The ulnar nerve is stimulated through surface electrodes, and the adductor pollicis
                muscle response is measured.

             -  After the stabilisation period, rocuronium 0.6 mg kg-1 (2 x ED95) will be injected
                intravenously during 5 seconds.

             -  The trachea will be intubated after a 95% depression of the first twitch

      5.1. Neuromuscular measurements

        -  Onset time = time from beginning of injection of rocuronium until a 95% depression of
           the first twitch (T1).

        -  Duration 25% = time from beginning of injection of rocuronium until 25% T1 recovery.

        -  Recovery index T25-75 = time between 25% T1 recovery and 75% T1 recovery.

        -  Clinical recovery T25 - 0.9 = time between 25% T1 recovery and TOF ratio (T1/T4) of 0.9
           (corresponding to safe extubation condition).

      5.2. Haemodynamics

        -  Blood pressure

        -  Heart rate These measurements will be done before (baseline), and at 5-minute intervals
           during the study drug infusion. Before and immediately after tracheal intubation,
           haemodynamic measurements will be repeated.

      5.3. Adverse events, safety

        -  Any minor adverse event (no need for intervention) or major adverse events will be
           recorded.
    

Intervention name(s): Physiologic saline; Magnesium sulphate
Intervention type(s): Drug; Drug
Intervention description(s): Intravenous infusion of the study solution, 1 ml per kg bodyweight, corresponding to MgSO4 60 mg kg-1 in the magnesium group and 1 ml per kg physiological saline. The infusion will be given with during 15 minutes.; Intravenous infusion of the study solution, 1 ml per kg bodyweight, corresponding to MgSO4 60 mg kg-1 in the magnesium group. The infusion will be given during 15 minutes.
Intervention MeSH terms: Magnesium Sulfate
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Neuromuscular block; Magnesium; Rocuronium; Time course of action