The AFL announced the current "three and one" bench system will be retained for season 2013, but an 80-rotations cap will be trialled during the NAB Cup.
A decision was set to be made over whether to retain the current one sub and three rotations system, to limit the bench even further by having two substitutes and two interchange players, a rule which was trialled in the 2012 NAB Cup.
The cap on rotations could instead be introduced for the 2014 home-and-away season onwards.
The two subs and two interchange rule was being considered to further decrease congestion around the ball.
But, McGuire sent out a blunt warning to league officials by declaring players could be forced to consider taking extreme measures to increase their endurance.
"They're driving players into taking EPO," McGuire told Triple M radio on Tuesday morning.
EPO, or Erythropoietin, is a naturally-produced hormone which increases red blood cell production.
The drug is abused by athletes to improve the delivery of oxygen to muscles and therefore produce a dramatic increase in stamina - and is at centre of the international cycling storm involving disgraced legend Lance Armstrong.
McGuire said the extreme measures may become more attractive to AFL players as the game gets faster and more competitive, with even less chance to rest.
"What's the logical conclusion to players being run off their feet and having to stay on the ground longer?" McGuire asked.
"The unintended consequence of these things is that you will drive players to look to be able to stay on the ground longer and I don't think they've thought it through."
The AFL will announce the decision on the bench rules later on Tuesday.