Defender Luke McDonald's potentially season-ending ankle injury has further soured a difficult night for North Melbourne at Marvel Stadium on Saturday night.

The Kangaroos seemed primed to post a sixth victory in seven matches when they hit the front 18 minutes into the final term, after trailing by 18 points at three-quarter time.

Those plans came unstuck in the final 30 seconds when a desperate Essendon foray ended with Anthony McDonald-Tipungwuti snapping his fourth goal of the night for the match-winner.

McDonald fractured the fibula near the ankle on his right leg, and caretaker coach Rhyce Shaw told reporters "it doesn't look good" in terms of him playing again this season.

Key forward Nick Larkey also left the game in the fourth quarter after again suffering from heart palpitations that have affected him throughout the season.

Shaw made a point of saying Larkey's issue was not on the same level as that of St Kilda's Dylan Roberton, whose AFL career is on hold because of his own heart problems.

"Nick's had heart palpitations and he's been managing that for a long time. Our doctors are all over that and they've put the processes in place," Shaw said.

"He just had a little turn tonight and obviously we'll assess him during the week, but I just saw him before and he seems fine.

"He's had it a couple of times (this season) and it's not a massive thing."

Another forward, Mason Wood (quad), was a late withdrawal, but is likely to return next week.

North's midfield has been a key cog in Shaw's success in his previous five games in charge – other than the Giants loss – but the Bombers took the honours on Saturday, particularly in the middle two quarters.

With Ben Cunnington tagged out of the contest by Dylan Clarke, none of skipper Jack Ziebell, young gun Jy Simpkin, Jed Anderson or Paul Ahern was able to have a major impact.

Some of that group came alive in the last-quarter surge, especially Simpkin, with three of his eight clearances in that period, but they fell narrowly short.

"I'm disappointed for the boys and I'm disappointed for everyone who came along tonight," Shaw said.

"We started well, got going (and) early on in that first quarter looked good, and then we just started to drift a little bit away from what we wanted to do.

"The boys just put their heads down in the last quarter and really went to work and it showed the fight they've got in them."

Shaw continues to make a strong case to be Brad Scott's long-term successor beyond this season.

Sydney coach and former star Roo John Longmire's decision on Friday to sign a three-year contract extension through the 2023 season only enhanced Shaw's hopes of staying on.

"It's good to see a former coach get another three years (and) he stays up there for another extended period, which is great for John," Shaw said.

"He's obviously a fantastic coach, a great coach. He's been in three Grand Finals, won one, and he deserves it – he's done really well up there.

"My situation tonight is not great, we just lost, so that's all I can worry about … I would love to coach these boys, they're a fantastic group of players, it's a fantastic club and there is some real excitement around it, but I can't worry about that.

"I have to take care of what's in front of us, and what's in front of us is a huge challenge and it is day to day. We've got to make sure we look after that and the rest will take care of itself."