Mikel Arteta was left in a difficult position against Manchester City due to a combination of injuries and mistakes by his Arsenal side on their Premier League return.
New Premier League regulations allow managers to make five substitutions per game from an increased bench of nine.
However, League rules state that managers can only make these changes at three different in-game stages, along with any they want to make at half-time.
Arteta was forced into two early changes at the Etihad, with Granit Xhaka and Pablo Mari both picking up injury problems.
Xhaka departed on a stretcher after eight minutes following a collision with a team-mate, while Pablo Mari was taken off soon after with David Luiz coming on in his place.
Those changes meant that unless Arteta made a change at half-time, he would need to make three subs at the same time in the second half if he wanted to change things up.
David Luiz made a costly mistake for Arsenal's first goal as he let a Kevin de Bruyne pass bobble off his leg through for Raheem Sterling to score - and worse was to come.
Luiz could not keep pace with Riyad Mahrez after the break and pulled down the City attacker for a penalty, earning a straight red card in the process.
De Bruyne duly scored the spot-kick, and that left Arsenal with 10 men - and Arteta with only one more opportunity to change his tactics.
With 66 minutes on the clock, Arteta made those changes: on came Alexandre Lacazette, Ainsley Maitland-Niles and Reiss Nelson; Joe Willock, Matteo Guendouzi and Eddie Nketiah departed.
