It is ultimately a very tricky task for multiple reasons.
If poor performance leads to a higher risk of acquiring debilitating effects, and debilitating effects lower performance, then a player can end up in a downward spiral. Even if it more luck than poor performance, you can still get that spiral effect if it is a case where messier or longer fights mean more opportunities for that bad luck to bite, as “poor performance” tends to result in longer and messier fights.
This also potentially makes a mess of difficulty levels and game challenge in general, as this widens the differences in players’ abilities.
Some will argue that the solution is an adaptive difficulty, but adaptive difficulty creates its own issues. Players seeking challenge can balk at the idea that a game gets easier for them when they make a mistake, to the point that they’ll restart just to keep the difficulty at its “proper” level. Adaptive difficulty also robs some of the consequence of long-term or permanent negative effects. Why even implement such injuries if the game’s challenge level will immediately compensate for having them?
Another concern is how such injuries affect how entertaining it is to play the game. Even if it had zero impact on the game’s difficulty, a permanent limp that cut your movement speed in half might produce enough frustration to drive many to simply quit if they weren’t already near the end. If a combat-focused game simply takes away half your combat options when you lose a hand, then beyond making the game more difficult, the hand loss will likely make the combat less interesting.
Beyond all of the above, you still have player psychology. Players tend to want to restart rather than be saddled with a long-term or permanent penalty.
If you go with non-permanent penalties that heal over time, but don’t put a time limit on the game itself, then you’ve just encouraged players to simply waste time to fully recover rather than to push forward. Worse, players will blame the game for being badly designed to “require” that they sit around for an hour to heal a bad leg before moving on. Similar can go for making the resource spent be something other than time. If it is money, then you’ve just encouraged players to grind some easy area to raise the funds rather than progress, and again players will blame the game’s design for the “requirement.” If it is a game that can only be progressed, then you again risk getting into a downward spiral situation.