The Effect of Magnesium Sulphate on the Time Course of Rocuronium Induced Neuromuscular Block

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.

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.

Eligibility Criteria:
Inclusion Criteria:

* American Society of Anaesthesiology (ASA) status I or II
* Adults, aged 18 years to 60 years
* Scheduled for elective surgery lasting longer than 120 min without need for continuous curarisation

Exclusion Criteria:

* A history of allergy or hypersensitivity to rocuronium
* Neuromuscular disease
* Preoperative medications known to influence neuromuscular function (for instance, certain antibiotics and anticonvulsants)
* Electrolyte abnormalities
* Hepatic or renal insufficiency
* Patients with a body mass index \<19 or \>28 kg m2
* Pregnant or breastfeeding women
* Expected difficult intubation or mask ventilation