As no one has answered this yet, here's my 2 cents.

3 main factors seem to affect this issue, the likelihood of such a release occuring, the environment which it occurs in and the consequences of such an exposure.

In order;

Is this likely to occur, has this ever occured, what could be done to prevent this from occuring?  Relying on RPE seems to be impracticable everytime you touch a gas cylinder - I doubt this is common practice. 

Is this outside in a well ventilated area, generally in my experience this (or laboratory or large workshops) are where most cylinders are stored.  If not can any higher risk tasks, valve / regulator changing be done in a safer area.  If outside & well ventilated, is there likely to be still a significant risk due to the immediate dilution or ability to move quickly away from any exposure.

Whilst nealry any gas, at any concentration if accidentally released directly into the breathing zone could have the ability to cause harm, if only by the displacement of Oxygen, some gases would of course be more harmful than others, are the gases you use inert or highly toxic?

Perhaps a step back would be to determine if HSG 53 is appropriate in the first place, though a sudden release is "possible", is it feasibly possible if you can have safe systems of work, procedures, training and supervision.  In my experience, I have never seen anyone using RPE when handling cylinders with 1 exception, I believe hooking methyl mercaptan cyclinders up to natural gas lines they used BA. 

Perhaps if you can share the job, the task (connecting / disconnecting?), the environment, the gases in question, someone in a similar position might be better able to share their experience than I.

Des

Thanks everyone; in answer to the questions;

Yes these are highly toxic gases.

These are used within a large laboratory and so the connections must be made when the cylinder is delivered to the lab from the external holding cages.

We have had a few instances in the past whereby through operator error (even though trained regularly) they have turned on a cylinder into their face before fully connecting the regulator etc. (luckily these were only air and nitrogen cylinders).