Nurses are preparing to ramp up strikes by involving A&E workers and staff from cancer wards in the next wave of walkouts over pay.
The Royal College of Nursing (RCN) is considering fresh action over three separate days, which would run throughout the night.
In a major escalation, the union is said to be poised to ask nurses working in emergency departments, intensive care units and oncology to join the strike.
It is also considering refusing to make local agreements with trusts to help hospitals during strikes, which it has previously done.
Staff would continue to provide minimum legal levels of care.
NHS leaders pleaded with Health Secretary Steve Barclay to hold pay talks to prevent "the biggest impact on patients we’ve seen".
Nurses have already taken part in several days of strikes since December as ministers continue to stonewall their pay demands.
Walkouts have already led to 137,000 appointments being postponed, with nearly 50,000 of those following last week's RCN walkouts, according to NHS Providers.
Rishi Sunak and Health Secretary Steve Barclay have been criticised for refusing to engage on wage demands for this year, instead seeking to shift focus to next year's pay deal.
An RCN source said: "NHS leaders are fearing this escalation and they must bring pressure to bear on Government to get it stopped.
"They were expecting an escalation but had not prepared for the removal of the committees and derogation process that too many had manipulated at local level and applied pressure on nurses to break the strike."
Dates for the next strike by nurses in England are expected to be announced within days.
The union must give two weeks notice for any walkouts.
RCN members went on strike in England last Monday and Tuesday but a walkout in Wales was cancelled following an improved pay offer from the Government in Cardiff.
RCN general secretary Pat Cullen has appealed to Mr Sunak for talks but a week later the Prime Minister has not replied and there has been no contact with the Department of Health.
Saffron Cordery, deputy chief executive at NHS Providers, said plans to escalate strikes further were "alarming given the significant impact they’ve already had on patients".
She said: "A continuous 48-hour strike that includes staff from emergency departments, intensive care units and cancer care services would likely have the biggest impact on patients we’ve seen.
"This will be significantly compounded if junior doctors also vote to strike from next month – further derailing efforts to tackle care backlogs."
Ms Cordery warned that frontline staff had been pushed to the brink over "challenging" working conditions and pay levels.
"The only way to avert more disruption is to bring the strikes to an end, which means the government must talk to the unions, now, about pay for this financial year," she added.
It comes as polling guru Lord Hayward said the strikes could torpedo Tory chances at the local elections.
The Conservative peer told The Telegraph: “The Government has to have a clear run into the local elections of several weeks to benefit from any progress.
“But you have this ongoing background noise in relation to the strikes.
"They would have to bring that to a close well before [the May elections]. People don’t respond to things quickly unless it is something very dramatic.
“If the strikes were settled, the polls would be in a very different state. As things stand, it is difficult for the Government to get other messages across.”
A Department of Health spokesman said: “The Health and Social Care Secretary has been clear he wants to continue discussing with unions what is fair and affordable as part of the 2023/24 pay process, including concerns around pay, conditions and workload to find ways to make the NHS a better place to work for everyone.
“He continues to urge unions to call off strikes and engage in a constructive dialogue about the Pay Review Body Process for the coming year.
“Our priority is keeping patients safe. The NHS has tried and tested plans in place to minimise disruption and ensure emergency services continue to operate.”
