This could be a little early in the season to discuss, but some owners do get concerned during the season when it happens. It is also the toughest thing to overcome when it does happen. So to help owners out and keep it in the back of your minds at least. It can also happen at the ML level and can be rather frustrating to overcome.
Some of the sudden fatigue problems at any level can be caused by an injury to a pitcher early in the game, extra inning games (I had three in a row once, destroyed my pen for a week), a bad outing by a starting pitcher.
The worst problem is an owner not caring for his minor league teams and that happens quite often. The biggest reason to care for your minor league teams is to keep them healthy and improve their ratings. Playing players with fatigue hampers their chances of improvement and makes them injury prone.
There is probably more than one way to do it. But this is how I do it. For one, I could care less if a minor league team actually wins or losses. It is more how they play the game. I do prefer them to win by the way. I either run 12 or 13 pitchers active depending except rookie where I run 17. I normally have 2 to 3 pitchers or more inactive at each level. Unlike some, if a pen pitcher fatigue level isn't at 100%, I rest him. If his recovery doesn't restore him to 100% the next day then I deactivate him and activate another that is rested. It doesn't matter if a pitcher stays active the entire season as some would say they must. I haven't seen any progression difference whether they are active or inactive. The entire key is getting them innings pitched. So I shuttle the pen in and out after every game where needed, yeah it may take a couple minutes but it is worth the time.
The biggest thing is the starting pitchers. Put their TPC at no more than plus 10 of their stamina, then add 15 for their MPC. The catch at doing this is to set the bull pen call to 1 or 2. I usually use 2. If you have health risk pitchers, do not use 1 on the call pen, use 2 or 3 for them (I use 3). This ensures that the rotation is not overly burdened and I don't have to change it unless I want to use a different pitcher or one gets injured. They also usually pitch around 6 innings per outing or more. If the rotation is not getting overly fatigued then increase the TPC by 5 after awhile and see if fatigue holds acceptable levels on the rotation.
The pen is also tough. You don't want no more than three actual relief pitchers and one should be the closer. Sometimes I don't even run a closer, but if you have one that is to be a closer, it is always real nice to put him there and set it so he only pitches the 9th inning. You can run with two setup types and the rest should be starting pitchers that you really could care less about as starters or middle relievers. The setup guys run their TPC and MPC to equal their stamina without going over. The other starting pitchers..errr..long relievers, set their TPC and MPC to half their stamina plus 5. I don't really make any distinction as to Long Relievers and Setup A in the minors, I call them all Setup A. That way I don't have to look as to what they are. The simmy will bring in the right one when needed. I may run a Mop Up pitcher if I am really mad at one of them for not being able to pitch well. The actual Setup guys I shuttle back and forth from active to inactive when needed and rest the others when needed. Another thing to set is the inning available to ANY except for the closer which would be 9.
One thing about a closer is that I rarely take him out of the closers role and rest him unless his fatigue level goes below 50 or recovery is more than 2 days, he is the only exception as they are seldom called on two days in a row.
I rarely have minor league fatigue problems using this formula, but it does take about 5 minutes to make sure things are all set and nobody is fatigued. My fatigue problems usually occur when one gets injured in an early inning and then I have to fight to right the ship for a day or two.
If you are not able to make changes to the pitching staff after each game, then another strategy is necessary. Run a 6 man rotation so you can put more burden on the starting staff. This will allow TPC to go up to 15 pitches over his stamina and 15 to MPC easily. Run an 11 man position staff making sure at least one backup can play all positions (whether he can or not) in case of injury then change position players out when needed. Making sure you change the Rest, Defense and Pinch Hit hierarchies is a must. Then use 14 pitchers with 8 in the pen and set the TPC and MPC where MPC is half their stamina. Four of the 8 should be SP types at least.
One thing I do in HI and Low A is make sure the SP's and Long relievers ...errr.. pseudo Setup A guys have a stamina greater than 65 and control in the 65 and up range. I do not care how ugly their splits are but do try to get ones with a pitch or two above 50.
Where do I get these guys? Usually I grab some from minor FA signings, Rookie League left overs that weren't worth promoting the season before and Try Out Camp.