Surprisingly easy.
-Always do this on Quake full nightmare run so you have most weapons and ammo
-When you start the level, take note of your armor. You almost certainly have some left from last level. If you take even a single point of armor damage, reload. There's no need to pick up armor (or health) in this run, but if you do, e.g. go to 150 armor, take note of that instead.
-Spam quicksaves, but always manual save after major encounters. Also, manual save before going underwater. Drowning damage counts! (In fact, ALL damage counts)
-For me, there were only two trouble spots (below). Otherwise, it's just a matter of sidestepping Fiends, mostly. Also: assume there are Spawns behind every corner. Super nailgun or lightning gun them before they even jump.
-Trouble spot 1: manual save before this. The wall pushes you to a room full of Spawns. You can actually spam grenades from the doorway before you trigger the wall to move. Go crazy, but there are a couple that survive. Keep spamming grenades while you are being pushed, then switch to super nailgun when you start to gain line of sight to the room. Quicksave, and ratatat-tat.
-Trouble spot 2: near the end, the altar room. Jumping from a water tunnel alerts Spawns and a vore. Did I mention manual saves before going underwater? Then use quicksaves to try, try again. Monsters should be dormant until you get out of the water. You should be able to blow them up with a super nailgun, shooting diagonally up from the right side of the tunnel. The enemies are on the left. Once you hear the Spawn booms and the Vore dying, quicksave, jump up and grab the quad damage. Be quick, remember that drowning damage stops the run! More Spawns will be alerted very soon, just keep moving and snipe them with nails or lightning gun. You might trigger the altar by accident, which will alert the Death Knight beyond the door. He will succumb to quad damage soon though.