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The Oilers visit the Vancouver Canucks on Thursday at 8:00 p.m. MDT. The game can be seen on Sportsnet One, and heard on 630 CHED and the Oilers Radio Network.
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Connor McDavid registered a goal and two assists, while his linemate Ryan Nugent-Hopkins notched one tally and one helper.
Edmonton went 1-for-3 on the man-advantage and 3-for-3 on the penalty kill.
Cam Talbot stopped 13 of 18 shots before being pulled. Laurent Brossoit made nine stops on 11 shots in relief.
Edmonton's offense halted at three, allowing Columbus to take control of the game.
"We got the start we wanted, up 3-0 and then I don't know what happened there," said Adam Larsson, who logged 22:30 of ice time. "I thought our defensive game today was not even close to where it has to be."
Six goals were scored in the opening 20 of Tuesday's match.
McDavid hogged much of the attention due to a three-point first-period performance, scoring shorthanded and dishing two helpers to confirm a new career-high in points with 102.
There's a list of accolades the Oilers Captain reached, becoming the eighth NHL player to record multiple 100-point campaigns by the age of 21 or younger; the first Oiler to record consecutive 100-point years since Mark Messier and Wayne Gretzky did through the 1986-87 and 1987-88 seasons; and the newest Oiler to score 40 in a campaign since Petr Klima in 1990-91.
"His game speaks for itself," said Andrej Sekera.
McDavid collected point No. 100 less than four minutes into the match with an assist on Nugent-Hopkins' 22nd goal.
Sergei Bobrovsky mishandled the puck in the trapezoid, gifting it to McDavid behind the net. He quickly dished it to Nugent-Hopkins in front for a tap-in 3:37 after opening faceoff.
A scary moment occurred on the following shift when linesman Steve Barton fell to the ground after McDavid was checked into the boards near the offensive zone blueline. Barton was taken off on a stretcher and the game continued with two referees and one linesman.