The top seed again dropped a set before coming home 6-3, 3-6, 6-3, 6-2 against dangerous Dane Holger Rune on Rod Laver Arena with both men needing medical attention.

Sinner struggled in the muggy conditions, his hand visibly shaking and his heart rate taken in the third set before he left court for a medical timeout.

Rune needed attention to a sore right knee in the same set.

They then had a bizarre 20-minute delay when Sinner demolished the metal brace that secures the net to the floor with a thunderous serve early in set four.

"It was for sure very, very tough," said Sinner, who is bidding to become the first Italian man to win three Grand Slam crowns.

"I tried to stay there mentally, I tried to stay connected with my service game and in my return game just seeing what happens."

Asked what his medical problem was, he was evasive.

"I had a strange morning because I didn't warm up today," he replied. "I knew in my mind already that I would struggle today."

The win put him into clash against Australia's big hope, eighth seed Alex de Minaur, or fast-rising young American Alex Michelsen.

The Italian is bidding to defend a Grand Slam title for the first time after winning the first of his two majors in Melbourne last year, beating Daniil Medvedev in the final.

It was the catalyst for a sensational year that saw him win eight titles, including the US Open and ATP Finals and his victory over 13th seed Rune extended his win streak to 18 matches.

The 23-year-old stamped his authority on the match immediately by breaking to love, with Rune hitting four consecutive errors.

Sinner's serve was iron-clad and there was no sniff for the Dane, who went one set down in 33 minutes.

But a Sinner double-fault in the eighth game of set two handed Rune a break, allowing him to hold and level the match as he began to find his rhythm.

It was the second set Sinner had dropped in the tournament, having not done so in 13 previous matches.

Sinner clung on to hold in an epic game three in the third set, which included a remarkable 37-shot rally that the Italian won to save break point.

He gave Rune another break point at 2-2 with a double fault, again saving, but he was labouring.

At the changeover, a doctor checked him and he went off for a medical timeout.

Sinner returned and slogged through a testing 14-point eighth game to break for 5-3 before sealing the set.

After the delay while the net was fixed, he produced a top-notch forehand winner to break for 2-1 in the fourth set and there was no way back for a tiring Rune.