Rapid Sequence Intubation With Magnesium-rocuronium Compared With Succinylcholine - A Randomised Clinical Study

Condition(s) targeted: Intubation Condtions

Intervention: Magnésium sulphate (Drug); Curarisation with rocuronium (Drug); Perfusion of Placebo (Drug); Succinylcholine (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University Hospital, Geneva

Official(s) and/or principal investigator(s):
Christoph Czarnetzki, MD, PD, Principal Investigator, Affiliation: University hospitals of Geneva
Martin R Tramèr, MD, PhD, Study Chair, Affiliation: University hospitals of Geneva
Christian Kern, MD, Prof, Principal Investigator, Affiliation: University Hospitals of Lausanne, Switzerland

Overall contact:
Christoph A Czarnetzki, MD, MBA, Phone: 0041223723311, Email: christoph.czarnetzki@hcuge.ch

Rapid sequence intubation (RSI) is the preferred method of endotracheal intubation in the emergency setting. The aim of RSI is to achieve rapid unconsciousness and complete neuromuscular blockade which facilitates endotracheal intubation. RSI is of particular importance in unfastened patients who are at risk of regurgitation and subsequent aspiration of stomach contents into the lungs during induction of anaesthesia.

Still today, succinylcholine is the neuromuscular blocking agent of choice for RSI. However, unfortunately in 60 at 80% the intubations conditions not are excellent and there are contraindications for the usage of succinylcholine and numerous side effects. Thus there is a need for alternative techniques that allow for rapid, high-quality and safe intubation conditions. Magnesium has an impact on neuromuscular transmission; it reduces the amount of acetylcholine that is released at the motor nerve terminal.

It has been shown that an IV infusion of magnesium sulphate prior to a standard intubation dose of rocuronium enhanced the speed of onset of the neuromuscular block compared with rocuronium alone by about 35% and there was much less variability in onset times. This makes the combination magnesium-rocuronium a potentially interesting alternative to succinylcholine for RSI.

The investigators objective is to compare in surgical patients during a standardised RSI procedure intubation conditions with rocuronium 0. 6 mg kg-1 after pre-treatment with intravenous MgSO4 60 mg kg-1 (experimental intervention) with succinylcholine 1 mg kg-1 (control intervention) and to quantify any minor or major adverse event.

The investigators primary hypothesis is that with rocuronium 0. 6 mg kg-1, after pre-treatment with MgSO4 60 mg kg-1, the rate of excellent intubation conditions will be higher (80%) compared with succinylcholine 1 mg kg-1 (60%).

This is a two centre (Division of Anaesthesiology, Geneva University Hospitals and Division of Anaesthesiology, University Hospital of Lausanne), stratified (male, female), randomised, double blinded study including 280 patients.

The investigators will compare in surgical patients during a standardised RSI procedure intubation conditions with rocuronium 0. 6 mg kg-1 after pre-treatment with intravenous MgSO4 60 mg kg-1 (experimental intervention) with succinylcholine 1 mg kg-1 (control intervention).

Intubation conditions will be evaluated by the intubating anesthesiologist following predefined criterias. The intubating anaethesist will not be present at study drug administration to guaranty blinding. Only two intubating anaesthetists will be identified per participating centre.

Rapid sequence intubation is a cornerstone of daily anaesthetic practice and succinylcholine is still the most frequently used neuromuscular agent in this context. In some patients, succinylcholine is contraindicated and therefore alternatives to this very fast reacting neuromuscular blocker are needed. If the investigators show that the investigators proposed magnesium-rocuronium regimen provides better intubation conditions as succinylcholine, the investigators study is likely to have an important impact on daily clinical practice.

Official title: Rapid Sequence Intubation With Magnesium-rocuronium Compared With Succinylcholine - A Randomised Clinical Study

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Intubation score

Secondary outcome:

Signs of histamine release

awareness and muscle pain

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Adult, age ≥18 to 65 years, male or female.

- American Society of Anaesthesiology [ASA] status I or II.

- Patient is able to read and understand the information sheet and to sign and date the

consent form.

- Patient scheduled of elective surgery lasting ≥60 minutes.

- If the patient is female and of childbearing potential, she must have a negative

pregnancy test.

Exclusion Criteria:

- A history of allergy or hypersensitivity to rocuronium, succinylcholine or magnesium

sulphate

- Neuromuscular disease

- History of malignant hyperthermia

- Preoperative medications known to influence neuromuscular function (for instance,

certain antibiotics [aminoglycosides], anticonvulsants [phenytoine], or IV lidocaine)

- Electrolyte abnormalities* (for instance, hypermagnesemia or hyperkalemia)

- Hepatic dysfunction* (i. e. bilirubin >1. 5 x upper limit normal (ULN), alanine

aminotransferase (ALT) >2. 5 x ULN, aspartate aminotransferase (AST) >2. 5 x ULN)

- Renal insufficiency* (i. e. creatinine >1. 5 x ULN, creatinine clearence < 60 ml min-1

1. 73 m-2, estimated by the formula by Cockroft & Gault)).

- Atrioventricular heart block

- Patients with magnesium treatment

- Patients with a body mass index <19 or >28 kg m2

- Pregnant or breastfeeding women

- Expected difficult intubation or mask ventilation.

- Patient having participated in any clinical trial within 30 days, inclusive, of

signing the informed consent form of the current trial.

Christoph A Czarnetzki, MD, MBA, Phone: 0041223723311, Email: christoph.czarnetzki@hcuge.ch

University Hospital of Geneva, Anesthesia Department, Geneva, Canton of Geneva 1211, Switzerland; Recruiting
Christoph A Czarnetzki, MD, MBA, Phone: 0041223723311, Email: christoph.czarnetzki@hcuge.ch
Christoph A Czarnetzki, MD, MBA, Principal Investigator
Christopher Lysakowski, MD, Sub-Investigator

Division of Anaesthesiology, University Hospital of Lausanne (CHUV), Lausanne, Vaud 1011, Switzerland; Recruiting
Sylvain Ganer, MD, Phone: 004121 314 11 11, Email: sylvain.gander@chuv.ch
Christian Kern, MD, Prof, Phone: 004121 314 11 11, Email: christian.kern@chuv.ch
Christian Kern, MD, Prof, Principal Investigator
Sylvain Gander, MD, Sub-Investigator

Starting date: September 2012
Last updated: September 21, 2012