If you thought Second Opinion was tough. Try New Blood
That said, New Blood makes some welcome changes to the difficulty and challenge of the operations.
Difficulty is the one area where New Blood has definitely improved. Now I came into New Blood expecting a challenge, and it didn't disappoint. I was actually shocked to find that my sharply honed surgical skills from Second Opinion didn't carry across as well as I'd hoped to NB. New Blood difficulty is leaps and bounds above SO's, and its a welcome change for me. I thought I'd breeze through hard mode, instead I had to relearn everything I knew.
Never did try out 2 player mode but I imagine that would make things too easy with 2 experienced players doing an operation together.
Again see my SO review because most of what it did right, NB does the same or better.