The Magpies need to win and hope Paris Saint-Germain fail to beat Borussia Dortmund to reach the last 16.
However, Newcastle's first-choice goalkeeper, Nick Pope, looks set to be out for four months with a dislocated shoulder.
Howe's second choice, Martin Dubravka, has since played in his absence but after their 4-1 defeat to Tottenham, there was bad news about his fitness.
Reports claim that he has been nursing a problem with his shoulder and he could be set to miss the visit of Milan on Wednesday night.
Speaking ahead of the match, Howe remained coy over the Slovak's availability, as well as that of Anthony Gordon and Sean Longstaff.
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"You can read into it whatever you want... [about all three being absent from training]," Howe said at the pre-match press conference.
"We're two days after a game so we're trying to manage players. We'll see who's fit for tomorrow."
If Dubravka is unable to play, then Karius looks set to start in between the sticks as he is the third choice goalkeeper in their 23-man squad, with three young goalkeepers also named on their B list.
Should he feature, it would be just the second appearance he has made for Newcastle since he initially signed in September 2022.
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His debut came in the Carabao Cup final defeat to Manchester United last season, with Pope suspended and Dubravka cup-tied.
Karius is no stranger to Champions League football as he featured in every match for Liverpool during the 2017/18 campaign.
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However, the 30-year-old suffered a dismal time in goal in the final as he was at fault for two of Real Madrid's goals as they won 3-1. This was his last appearance in the competition.
A huge tie against Milan could spell the chance for redemption for him though, with Newcastle so close to qualifying out the group.