Prime Minister Benjamin Netanyahu’s administration has responded with its most searing assault on the Hamas-controlled Gaza Strip in years, announcing a full-scale siege of the already blockaded territory, and signaling that it’s preparing a ground invasion. Israeli commanders said the strikes were aimed at destroying Hamas’s military capabilities and killing senior leaders.

But the civilian toll has been extensive, bloody, and rapidly increasing. Gaza is home to more than 2 million people packed into a space less than half the size of New York City, with no safe passage as bombs rain down. The Gaza Health Ministry said Wednesday that at least 5,339 people had been injured during the four-day bombing campaign, 60 percent of them women or children.

The diesel supplies on which hospital generators depend are running out, health officials and health professionals said. The enclave’s sole power plant shut down on Wednesday afternoon for lack of fuel. The Palestine Red Crescent Society said four of its medics were killed as Israeli strikes targeted two ambulances in 30 minutes.

Overwhelmed medical facilities were prioritizing the worst shrapnel, burn and crush injuries for surgery, doctors said. The grounds of al-Shifa Hospital, Gaza’s largest trauma treatment center, was packed with families seeking safety.

Ghassan Abu-Sitta, a plastic and reconstructive surgeon at the facility, said his team operated on a young girl Wednesday morning whose nose had been ripped off and eyes were severely damaged by shrapnel. “Her mother was a doctor at al-Shifa Hospital,” he said. “Our staff doing the operation knew her well and now they were operating on her children.”

In between surgeries, he said the faces of the staff creased with worry as they checked their cellphones for news of loved ones while airstrikes continued outside. With the communications network patchy, their messages often failed to go through.

“Unless there is a humanitarian corridor that allows supplies in too, the health system is going to collapse,” Abu-Sitta said.

U.S. Secretary of State Antony Blinken left for a trip to Israel and the region on Wednesday to show support for Israel while addressing some of the humanitarian challenges, including the civilian exit from Gaza.

“We have the back of Israel. We have their back today. We will have it tomorrow. We will have it every day,” Blinken told reporters at Joint Base Andrews before leaving.

At least 22 U.S. citizens have been killed and 17 others are unaccounted for, U.S. officials said Wednesday.

The USS Dwight D. Eisenhower aircraft carrier strike group was deploying to the Mediterranean to bolster the U.S. military presence in the region, White House spokesman John Kirby said. The movement was long planned and isn’t in reaction to the situation in Israel, he said, but the carrier will be available if necessary, joining a second U.S. Navy aircraft carrier group that moved to the eastern Mediterranean earlier this week.

Israel and its allies are worried that other military actors in the region — including Hezbollah, in Lebanon, and its backer Iran — will take advantage of the conflict to open a multi-front conflict.

Israeli authorities warned Wednesday of a “suspected infiltration” from Lebanon but later said an incursion had been ruled out.

The audacity of the Hamas attack early Saturday has prompted growing anger at the apparent failure of Netanyahu’s government and military leaders to see it coming or spread security forces adequately along the Gaza border.

Israel on Wednesday announced an emergency wartime cabinet including Netanyahu, Defense Minister Yoav Gallant, and National Unity party leader Benny Gantz. “During the period of the war, no bills or government decisions will be advanced that do not concern the conduct of the war,” Netanyahu and Gantz said in a joint statement.

Netanyahu, a three-time prime minister, returned to the office last year as head of the most right-wing and religiously conservative government in Israel’s history. His third term has been defined by widespread street protests by Israelis opposed to his government’s plans to weaken the Supreme Court, and growing fears among Palestinians as hard-line ministers championed the expansion of illegal Jewish settlements on Arab land.

The Yesh Din monitoring group said Wednesday that it had recorded the killings of 19 Palestinians by armed settlers in the West Bank in five days.

On the highway that stretches south along the Gaza Strip, the Israeli military has bulldozed defensive berms around a dozen artillery positions. On Wednesday, soldiers called out coordinates before loading artillery shells that boomed toward Gaza at a rate of several a minute. Black clouds billowed over the horizon in the distance as they met their mark.

On the outskirts of Kibbutz Beeri, where rescue workers have recovered the bodies of more than 100 Israelis, soldiers set up mortar positions and reinforced them after hiding militants attacked again on Tuesday. Militants in Gaza have fired barrages of rockets into Israel since the crisis began, wounding scores of people.

More than 263,000 people have been displaced in Gaza since the fighting began, according to the U.N. Office for the Coordination of Humanitarian Affairs. Israel has warned civilians to leave, but there’s no exit: The border crossing into Israel is closed, as is the gate to Egypt, after it was damaged by an Israeli airstrike.

The Biden administration remained in “active discussions” with Egypt and Israel to help civilians leave Gaza, Kirby said Wednesday.

Israeli authorities said Tuesday that killing senior Hamas officials had become a top priority; they appeared to have been targeted in attacks overnight. Hamas said the family home of Mohammad Deif, leader of the organization’s military wing, was hit, killing his brother.

Deif’s house, which was empty, was also targeted, Hamas’s representative in Lebanon, Ahmed Abdulhadi, told The Washington Post. The whereabouts of Deif, who announced the assault on Israel on Saturday, are unknown.

The Israeli military said its aircraft also struck and killed Zakaria Abu Maamar, a member of the Hamas political bureau. Hamas confirmed his death and that of another member of its political office.

Fighter jets also hit the Islamic University, which the IDF said had been used as “a Hamas training camp for military intelligence operatives, as well as for the development and production of weapons.” It was not immediately possible to verify that claim.

The fate of more than 100 hostages taken by Hamas militants to Gaza during Saturday’s assault has consumed the Israeli public even as they have been burying their dead. Pope Francis called Wednesday for their immediate release.

“I’m praying for those families who saw a day of feast transformed into a day of grief; I’m calling for hostages to be released right away,” Francis said. He urged diplomacy, as terrorism and extremism “won’t help reach a solution to the conflict between the Israelis and the Palestinians, while feeding hate, violence, revenge, and hurting both.”

The Israeli military has called up 360,000 reservists, the largest mobilization since the 1973 Yom Kippur War, when 400,000 reservists were summoned. Nearly 4 percent of the country’s 9.8 million people have left their jobs and families to join the fight. Israelis abroad were scrambling to secure transportation home as airlines suspended flights.

With hostilities erupting along usually quiet regional fronts, the burgeoning crisis has sparked fears of a wider conflict. On Wednesday, Hezbollah and Israel, already notionally at war, exchanged fire along the Israel-Lebanon border.

The IDF said antitank missiles were launched at its soldiers and it was responding with strikes into Lebanese territory. Hezbollah then announced it launched rockets in response to the killing of three members by earlier Israeli shelling.

Loveluck reported from London. Dadouch reported from Beirut. Birnbaum reported from Washington. Meg Kelly in Washington, Noga Tarnopolsky in Jerusalem, Ellen Francis in London and Stefano Pitrelli in Rome contributed to this report.