Kiev, Ukraine (CNN) -- Long-simmering tensions exploded anew in Ukraine as clashes between police and anti-government protesters left at least 21 people dead and the capital's central square afire into early Wednesday.
President Viktor Yanukovych will address the nation after meeting with the opposition, Yanukovych's advisers told local media. The exact time for the address has not been announced.
Opposition leader Vitali Klitschko went to Yanukovych's office for talks after hours of clashes Tuesday continued early Wednesday.
The fresh violence in Kiev comes amid monthslong turmoil in what is essentially a fight over whether the country's future is alongside Russia or Europe, the latter favored by protesters.
Police confirmed the unrest has spread outside the capital of Kiev to western Ukraine, with protesters attacking police and local government offices in a number of regions.
Explosions ruptured the night air, but it was unclear whether they emanated from protesters' fireworks or a police action. Protesters fed several fires by tossing wood upon the bonfires in Independence Square, which was under the demonstrators' control.
Hundreds of protesters formed human chains passing bricks, rocks, wood -- any projectile for front lines -- and built barricades against a potential police offensive as Tuesday night became Wednesday at Independence Square, located about three blocks from parliament.
In those post-midnight minutes, Ukrainian security forces advanced against some barricades and used stun grenades and water cannons against protesters. Once police gained some ground, they relented and eased. Protesters in the heart of Independence Square threw rocks at police.
With more than 40 police officers injured in clashes with protesters favoring a European Union pact, ominous warnings were issued by Kiev officials and the U.S. Embassy.
City Hall officials warned residents to stay away from the city center "to avoid casualties," and the U.S. Embassy said Ukrainian security services "may take extraordinary measures" following the fiery violence.
The U.S. Embassy "advises all citizens to maintain a low profile and to remain indoors tonight," the mission said Tuesday.
In addition to seven police officers, the 19 people dead included 11 protesters and an employee from the ruling party's headquarters, officials said.
U.S. Vice President Joe Biden expressed "grave concern" over the crisis, in a phone call with Yanukovych.
"The vice president made clear that the United States condemns violence by any side, but that the government bears special responsibility to de-escalate the situation," the White House said in a statement.
Protesters set Independence Square afire Tuesday night by burning tires, spewing black smoke through Kiev.
Meanwhile, Arseniy Yatsenyuk, one of the opposition leaders, made a public appeal to Yanukovych: "Do not let Ukraine become a country covered with blood. Pull back the police and announce a cease-fire. Then we will negotiate."
Stefan Fule, the European Union's commissioner for enlargement and European neighborhood policy, expressed alarm at the violence.
"To learn that there have been deaths and hundreds of injured people makes me shake. I deplore deaths of those people and my thoughts are with their families," Fule said.
"I was just on the phone with the acting Prime Minister (Serhiy) Arbuzov telling him that seeing in the streets Berkut, the special police, with Kalashnikov(s) is source of great concern," Fule added. "He assured me that he and the government would do what they can to make sure that those weapons stay silent. For the sake of Ukraine and its future I will pray that he is right."
U.S. Secretary of State John Kerry condemned the violence.
"Rather than issuing ultimatums, the government of Ukraine should immediately resume talks with senior opposition leaders and support dialogue through Ukraine's democratic institutions, including parliament, the Rada," Kerry said. "We also call on protesters to refrain from violence of any kind; Ukraine's deep divisions will not be healed by allowing more innocent blood to be spilled."
U.S. Ambassador Geoffrey Pyatt said he hoped the government and opposition will take steps to reduce the escalation of violence "and the return to political dialogue."
"We want to see a Ukraine that is stable and democratic," Pyatt said.
The Interior Ministry said metro stations were closed.
The protesters' medical service said more than 150 people were hurt in Tuesday's clashes.
Thousands of demonstrators have packed Independence Square since November, when Yanukovych reversed a decision to sign a trade deal with the European Union and instead turned toward Russia.
The unrest intensified after an anti-protest law went into effect. Throngs of demonstrators took to the streets to protest the law.
More than 2,000 people have been injured during the clashes.
Portrait of violence
As temperatures hovered around freezing about 10:30 p.m. (3:30 p.m. ET), Independence Square was the central theater for the protest, as it has been for the past three months since it was first occupied and turned into a large fortified camp with barricades.
Authorities had vowed to clear the central Kiev square earlier in the day, moving in with force that proved fatal for protesters and police alike.
Video from earlier Tuesday showed riot police forcing their way through protesters, many officers carrying shields and swinging sticks. A few protesters responded by swinging bats themselves, contributing to a violent, chaotic melee in the center of the capital.
The situation hardly calmed as night descended. Fires raged around the square, with small explosions regularly erupting -- the product of protesters' fireworks and, perhaps, the stun grenades that police have been using to clear the crowds.
Authorities have used water cannons and restricted traffic into Kiev as part of their effort to clamp down on what it called "anti-terror" operations.
"The truce has been broken," said Viktor Pshonka, Ukraine's prosecutor general, in blaming the opposition for the rising violence and rationalizing the stepped-up response. "For the sake of pursuing their own political interests, they neglected all previously reached agreements and put lives and the peace of millions of Kiev residents under threat."
On Tuesday, the casualties occurred after protesters set fire to the headquarters of the ruling Party of Regions and as violence roiled the capital for the first time in more than two weeks.
Speaking from the protesters' medical facility outside the parliament building, Olesya Orobets said ambulances had been barred from the area.
The prosecutor general, who said in a statement that at least 100 people had been hurt, blamed the protesters for the violence.
"Today, we were able to see that only the government is interested in peaceful resolution of the situation," Pshonka said. "Opposition leaders should take the responsibility for everything happening in the street of Kiev today. It is the opposition who announced a peaceful rally that turned into violent standoff."
He vowed to hold the organizers accountable "for every single person injured, every car burned and every window broken."
United Nations Secretary-General Ban Ki-moon took note of renewed efforts in the Ukraine for meaningful dialogue, but expressed concern about the violence and appealed to all participants to act with restraint, his spokesman said.
In Britain, Foreign Office Minister for Europe David Lidington said in a statement that he was "appalled" by the reports. "This has no place in a European democracy," he said. "I condemn the violence and urge all sides to immediately de-escalate the situation."
He called on Ukraine to use a return to stability to tackle the protests' underlying causes -- "corruption, impunity, and the lack of checks and balances within the current governmental system."
A sliver of hope for a restoration of calm had emerged Sunday, when the government agreed to drop charges against demonstrators in exchange for the protesters' agreement to leave Kiev's City Hall and unblock streets in the city center, which they had occupied for almost three months.
But violence erupted again Tuesday, after the speaker of the parliament would not let opposition members register amendments that would have led to a vote to limit the rights of the President and restore the constitution to the way it was in 2004.