US Senate Republicans have voted in favour of a floor debate on their efforts to re-write healthcare policy, with Vice President Mike Pence breaking the tie.

The Senate on Tuesday decisively rejected a Republican proposal to repeal-and-replace Obamacare as Senator John McCain returned from Arizona to applause from fellow senators to cast a critical vote for Republicans, CNN reported.

The floor debate will on Wednesday morning continue to overhaul the Affordable Care Act, even though there are no guarantees the votes are there to eventually pass the bill.

Two GOP senators — Susan Collins and Lisa Murkowski — sided with all Democrats in opposition, meaning all remaining Republicans and Pence were necessary for the motion to pass.

The vote came as Senate Majority Leader Mitch McConnell and President Donald Trump dared their fellow Republicans to block their seven-year campaign promise to repeal and replace Obamacare.

The vote dealt with a measure that combined a previous Senate proposal known as the Better Care Reconciliation Act — that was rejected by several Republican senators — with $100 billion extra money for people on Medicaid desired by moderate Republicans and a proposal from conservative Senator Ted Cruz to allow bare-bones health insurance plans.

Democrats moved successfully to kill the amendment as it had not been officially scored by the Congressional Budget Office and therefore didn't meet the complicated reconciliation rules to consider the bill.

The senators will on Wednesday cast a vote on a "repeal-only" proposal. It too is expected to be defeated because many Republicans and Democrats reject repealing without a replacement ready.

Trump, who has repeatedly said he's ready to sign any repeal legislation, celebrated the vote, which creates a path to give him the major congressional victory that's eluded the White House thus far.

"I'm very happy to announce that with zero of the Democrats' votes, the motion to proceed on healthcare has moved past and now we move forward towards truly great healthcare for the American people. We look forward to that. This was a big step," Trump said.

"I want to thank Senator John McCain," he added. "A very brave man. He made a tough trip to get here."

But Trump also acknowledged there's a long road ahead for the legislation and criticised the two Republicans for opposing the motion.

"We had two Republicans that went against us, which is very sad, I think," Trump said. "I believe now we will, over the next week or two, come up with a plan that's going to be really, really wonderful for the American people."

Democrats are united against the bill, saying it would end healthcare coverage for millions of Americans.

"Anyone who thinks this is over is sadly mistaken," said Minority Leader Chuck Schumer.

"There are many, many Republicans who don't like this bill, who don't want to vote for it. They are under enormous pressure to vote for it. Anyone who voted to move to proceed and certainly anyone who votes to send this bill to conference is virtually voting to kick millions off healthcare, to make it much harder to get coverage if you have a pre-existing condition, to slash Medicaid and give a huge amount of tax cuts to the rich."

Senator Bernie Sanders on Monday called the bill the "cruelest, most destructive and irresponsible piece of legislation ever brought to the US Senate in the modern history of this country".

Paul, a Kentucky Republican, said he would support the procedural motion to open debate on the bill, so long as leadership guarantees a vote on a full repeal of Obamacare.

"If this is indeed the plan, I will vote to proceed and I will vote for any all measures that are clean repeal," Paul tweeted. Such an amendment would be expected to fail, however.

Heller, who has complained that Obamacare repeal efforts could hurt Nevada residents dependent on Medicaid, said hed would vote to move forward. Heller is facing a tough re-election campaign in Nevada in 2018.

"Obamacare isn't the answer, but doing nothing to try to solve the problems it has created isn't the answer either," Heller said. "If the final product isn't improved for Nevada, then I will not vote for it; if it is improved, I will support it."