MagA: Making Airways Great Again?

Today I have a quick analysis of a recent randomised controlled trial that look at the efficacy of magnesium for the optimisation of intubation conditions in patients NOT receiving neuromuscular blockade.

Here is the link to the paper:

Intravenous magnesium sulfate improves orotracheal intubation conditions: A randomized clinical trial. Imen Zouche, Wassim Guermazi, Faiza Grati, Mohamed Omrane, Salma Ketata, Hichem Cheikhrouhou. Trends in Anaesthesia and Critical Care 57 (2024) 

This is a single-centre, randomised, placebo-controlled trial. The authors have done a good job of blinding the participants.

Lets do a quick PICO to describe this trial and then we will look at the outcomes and my interpretation.

POPULATION: This was a small trial that ultimately randomised 80 adult patients undergoing elective surgery in a single Tunisian hospital. They were almost all having abdominal or orthopaedic surgery. These were relatively healthy (ASA 1 or 2) patients who did not have any predictors of difficult intubation. The authors also excluded patient from the trial who had unanticipated difficult airways which is an unusual decision. The patients underwent a very standardised anaesthesia cocktail of medications and techniques which are reasonably standard practice.

INTERVENTION: The intervention group received a pre-induction infusion of 50 mg/kg (IBW) of magnesium sulfate (based on ideal body weight) dissolved in 100ml of normal saline over 15 min. This was prepared by a second anaesthetist once the randomisation was complete. For those working in mmol – a typical 70 kg man would get 3.5 grams of MgSO4, which is 14 mmol – that is about 1 and a half ampoules of the 2.5g/5mL mixed into a 100 ml bag of saline.

CONTROL: The control group received an identical 100 ml infusion of normal saline over the same 15 minutes immediately pre-induction.

The standardised anaesthetic induction mix was a generous 3 μg/kg of fentanyl, followed by 3mg/kg of propofol, and then orotracheal intubation was performed by an experienced anesthesiologist who was not involved in the study.  No neuromuscular blocking agents were given unless there was airway / intubation difficulty and then 1 mg/kg of suxamethonium was given after 60 seconds of unsuccessful intubation.

OUTCOME(S): The authors measured intubation conditions using the Copenhagen scoring system which is the recommended tool for anaesthesia research developed in the European Anaesthesia community and most recently updated in 2023 (Acta Anaesthesiologica Scandinavica Volume 67, Issue 8 Sep 2023 Pages993-1137). This is a composite scoring system that uses three measures:

Intubation conditions were considered:

1. Excellent if all 3 of easy laryngoscopy, abducted cords and no reaction to intubation occurred.
2. Good if all measures were either excellent or good
3. Poor if any of the “poor” factors was present

This seems like a reasonable metric – however there is some subjectivity to the “ease of intubation” and we are terrible at judging time in scales of 5 seconds. It does not seem that video was used either to record the laryngoscopy or the patient reaction to intubation – this would seem to be a simple way to make the outcomes more subjective.

I do like the fact that they have presented the data in a sensible manner. What we really care about here is whether the tube was easy (for the tuber and the patient) vs. were there any “poor” conditions – which would make the procedure unacceptable. Looking at the data in a dichotomised manner is more useful than a scalar or continuous variable. I just want to know if it will do the job!

RESULTS:

I am just going to paste the key results from Table 3 of the paper in here:

Those are some impressive numbers! The magnesium group was a clear winner. If you look at hte rate of Rescue Sux used it was also 1 vs. 5 patients in the saline control group. The “Clinically Acceptable” bottom line was 95% vs 39 %… thats an NNT of 2! Surely it must be too good to be true?

So let us back up the truck and think this through. Is there biological feasibility? What did we think before we read this paper? What are the down sides and does this data help us quantify these?

There certainly is biological feasibility – we know that magnesium tends to relax muscle and blunt the response to stimulation in other settings eg. asthma, seizures, salbutamol toxicity …

There have been a number of small trials looking at Mg+ effects on airway reflective stimulation. There are also quite a few positive trials that show magnesium as an adjuct to traditional paralysis drugs to facilitate intubation. None are that large or convincing to make magnesium a core part of elective anaesthesia practice.

This current trial is small – 80 peeps. So there is unlikely to be any reliable safety data here. There was no significant difference in haemodynamics in this trial – thought the numbers in magnesium group did seem a little less labile. There was no detected magnesium side effects – although he patients were all asleep and could not really let us know if they felt odd or dopey.

Recall – small trials exaggerate effects. What looks like a potent effect on intubating conditions in this small trial will almost certainly be watered down if this trial was repeated in a large, multi-centre, real world context. We also may see more harms in a bigger trial: even a single, rare; but severe adverse event from magnesium toxicity could change the whole game.

Lastly, a word of caution. These are well, elective surgery patients. These are not crashing septic octogenarians or acidotic diabetics on the brink or collapse. We need to be circumspect when translating this data from the operating room to our resuscitation bay or ICU.

The exclusion of patients with unanticipated difficult airway / intubation is very unhelpful. This occurred in about 5% of cases and their exclusion limits the external validity of this data. Ultimately, this is the group that we really care about – mostly we can intubate most punters with enough sedation / analgesia… it is the “tough tube” group where I want to know if magnesium will make it better or not.

My Bottom Lines:

1. Magnesium does seem to facilitate intubation in the absence of neuromuscular blocking agents.
2. This is probably worth using in well patients where we are wanting to avoid NMB agents for intubation.
3. We need to see more data from our sicker, non-elective population before we start using this in that setting. However, if this were to pan out it would be a very useful trick in those cases where we want to keep our patient breathing and pass a tube quickly.
4. I think that there is enough here to make a great ED airway trial! Bring it on.