WASHINGTON — Senate Republican leaders scrambled Tuesday to keep alive their plans to overhaul the 2010 Affordable Care Act and postponed a key procedural vote as a growing number of senators expressed doubts about the measure after the release of a fresh budget analysis.

The current proposal by Senate Majority Leader Mitch McConnell, R-Kentucky, would cause an estimated 22 million more Americans to be uninsured by the end of the coming decade while reducing federal spending by $321 billion during that time, the Congressional Budget Office concluded Monday.

The forecast by Congress’ nonpartisan budget scorekeepers appeared to rapidly erode Republicans’ confidence in the bill, with at least four GOP lawmakers saying by the evening that they would vote against even a procedural motion to start debate.

The release of the 49-page CBO report late Monday afternoon provided a new hurdle for the bill, which leaders hope to bring to a vote by Friday. No new senators immediately said they would back the legislation, and Sens. Susan Collins, R-Maine, Rand Paul, R-Kentucky, and Ron Johnson, R-Wisconsin, signaled that they would vote against starting debate Tuesday on the bill in its current form.

“I have so many fundamental problems with the bill that have been confirmed by the CBO report, that it’s difficult for me to see how any tinkering is going to satisfy my fundamental and deep concern about the impact of the bill,” Collins told the Bangor Daily News on Tuesday afternoon.

A fourth senator, Dean Heller, R-Nevada, had expressed his opposition last week, and has not shown subsequent signs of changing his mind.

Collins, a moderate Republican, tweeted that the measure would “ hurt [the] most vulnerable Americans” and failed to solve the problems of access to care in rural Maine, where, she wrote, “hospitals are already struggling.”

Others signaled that while they would vote yes on the procedural motion, they remained undecided on the bill itself.

In a sign of the challenge Senate Republicans face in mustering enough votes, Majority Whip John Cornyn, R-Texas, said the procedural vote is likely to be scheduled for Wednesday rather than Tuesday.

With Vice President Pence ready to cast a tiebreaking vote on the measure, Republican leaders can lose only two of their 52 members to pass the bill, which no Democrat is expected to support.

By late Monday, several GOP senators and aides appeared nervous and unsure about the path forward. They hedged on the timing of that procedural vote and suggested that the workweek could stretch beyond Friday. Further complicating the effort were at least two senatorial absences Tuesday: that of Sen. Jeff Flake, R-Arizona, whose father died Monday; and Sen. Mazie Hirono, D-Hawaii, who is undergoing cancer surgery.

Hirono’s spokesman Will Dempster said she is committed to returning “as quickly as she can” to the Senate.

Despite several Republicans’ public opposition, Senate leaders held out some hope for salvaging the effort, pointing to the CBO’s estimates of deficit savings as a silver lining that allows them to allocate additional funds to try to ease some members’ concerns.

If the Senate version does emerge, House leaders have not ruled out the possibility of a quick vote without negotiating the differences with their own bill, passed out of the House in May. Ultimately, the measure appeared to be teetering between two dramatically different outcomes — a rapid defeat and an equally rapid path to President Donald Trump’s desk.

House Speaker Paul Ryan, R-Wisconsin, would not say Tuesday how his chamber would act if the Senate passes a health care bill this week, saying, “We just don’t know what the final bill is going to look like.”

But multiple House GOP aides said Monday that there was a possibility that the leader would take a Senate-passed bill and try to move it through to final passage before the July 4 holiday. The GOP whip office advised members that “additional legislative items are possible” beyond what is scheduled for the week.

“I would not bet against Mitch McConnell,” Ryan said, downplaying the chances that the bill could stall. “He is very, very good a getting things through the Senate even with this razor-thin majority.”

Senate leaders quickly began working with undecided senators to determine whether any skeptics could be won over with additional spending on priorities such as expanding incentives for health-savings accounts favored by conservatives or a fund to help battle opioid addiction favored by Sens. Rob Portman, R-Ohio, and Shelley Moore Capito, R-West Virginia. Leaders can spend about $188 billion on increased spending without running afoul of Senate budget rules.

Asked whether McConnell and other Senate leaders have the support they need to pass the measure, Sen. Roy Blunt, R-Missouri, responded, “Anyone would tell you they don’t.”

Rep. Mark Meadows, R-North Carolina, chairman of the hard-right House Freedom Caucus and a key player in the passage of the House health bill, warned Tuesday that House passage of a Senate bill is not assured.

“If it’s predominantly the bill that is currently in the Senate, without significant amendments, there would not be enough votes in the House or the Senate to pass it,” he said.

Cornyn, R-Texas, went out of his way to blame Democrats for not cooperating — a talking point Republicans are expected to underscore if their bill is defeated.

The CBO estimated that two-thirds of the drop in health coverage a decade from now would fall on low-income people who rely on Medicaid. And among the millions now buying private health plans through ACA marketplaces, the biggest losers would roughly parallel those under legislation passed recently by the House: The sharpest spike in insurance premiums would fall on middle-aged and somewhat older Americans.

Its analysis of the Senate measure’s impact on federal spending — $321 billion saved over a decade — compared with $119 billion for the House’s version.

Paul — who spoke to Trump on Monday and will meet with him at the White House on Tuesday — called the Better Care Reconciliation Act “a terrible bill” on Monday, and repeated his contention that it would not go far enough in repealing the sprawling health-care law enacted seven years ago by a Democratic Congress and president.

Another conservative critic of the plan, Sen. Ted Cruz, R-Texas, would not say Tuesday whether he would vote to proceed with the bill.

“It remains a work in progress,” said Cruz, who has said he cannot support it in its current form. “My focus is on lowering premiums.”

And Sen. Marco Rubio, R-Florida, who remains undecided, said he was meeting privately Tuesday with Florida Gov. Rick Scott and McConnell. He said he supports bringing the bill up for a vote, and might propose amendments to the way the bill addresses Medicaid.

“You can’t amend a bill that is not up,” Rubio said.

McConnell took to the Senate floor just before the report’s release to press anew for rapid action. He made it clear that the bill, already tweaked early Monday, could be negotiated further to try to win over holdouts.

“The American people need better care right now,” McConnell said. “This legislation includes the necessary tools to provide it.”

Democrats quickly seized on the CBO’s projection of how much the ranks of the uninsured would grow.

“Republicans would be wise to read it as a giant stop sign,” Senate Minority Leader Charles E. Schumer, D-New York, told reporters. “No matter how the bill changes around the edges, it is fundamentally rotten at the center.”

Former CBO director Doug Holtz-Eakin, a Republican who is now president of the American Action Forum, said the report draws basically the same conclusions as the budget office’s earlier analysis of the House measure. He predicted that GOP senators are “going to get beaten on the head with the CBO report like it’s a club.”

The fresh figures come as Trump, in a sharp pivot from the praise he initially lavished on the House bill, has been urging the Senate to provide Americans with more generous health insurance.

On Monday, the White House again sought to cast doubt on the budget office’s credibility. “The CBO has consistently proven it cannot accurately predict how health-care legislation will impact insurance coverage,” it said in a statement.

According to the latest report, the Senate bill would mean that an estimated 15 million fewer Americans would have coverage next year, compared with the number if the ACA, commonly called Obamacare, remained in place. At the end of the decade, the 22 million increase in the ranks of the uninsured would include 15 million low-income Americans who would otherwise be on Medicaid and 7 million with private insurance.

That figure, about 1 million less than the House bill, would be equivalent to all the residents in 16 states — Kansas, New Mexico, Nebraska, West Virginia, Idaho, Hawaii, New Hampshire, Maine, Rhode Island, Montana, Delaware, South Dakota, North Dakota, Alaska, Vermont and Wyoming — losing health coverage.

The Senate plan would reduce federal spending to help people afford premiums for individual health insurance policies significantly more than under the House version. The Senate’s version would cut spending on tax credits by $408 billion by 2026 — compared with a $276 billion reduction in the House plan. The difference, in part, is because the Senate’s version would not permit people with incomes between 350 percent and 400 percent of the federal poverty level to qualify for tax credits and would restrict federal help to health plans sold through the ACA’s marketplaces. The Senate would tie the tax credits to skimpier health plans than the current subsidies.

And while the Senate bill would phase out the ACA’s Medicaid expansion more slowly than the House legislation, cuts to the public insurance program for the poor still would account for by far the largest share of the reduction in federal spending under the Senate bill — $772 billion over the coming decade.

In a briefing for reporters, CBO staff members said that they had not analyzed the bill’s effects on Medicaid cuts beyond the coming decade but that the reductions inevitably would be greater for a second decade.

It would also repeal or delay all of the taxes imposed under the 2010 law, including a tax on richer Americans’ net investment income, an annual fee for insurers, an increase in the hospital insurance payroll tax for the wealthy and the “Cadillac” tax on employers’ more generous insurance benefits.

Washington Post writers Mike DeBonis, Amy Goldstein and Ed O’Keefe contributed to this report.