Hundreds of protesters dug in around Nicaragua on Saturday, blocking roads as at least eight more people were killed in a 24-hour period.
Unrest has resumed since week-long church-mediated talks between the government and opposition to quell a month of violence broke down late on Wednesday.
Hundreds of demonstrators in the north, center and south of the Central American nation were blocking highways on Saturday, demanding Ortega and his wife, Vice President Rosario Murillo, stand down.
Since protests began on April 18 at least 83 people have been killed and more than 860 wounded, police and rights activists say.
Four people were killed on Friday, and another four by mid-day Saturday, police and family members said.
Ortega, a former Sandinista guerrilla who first ruled between 1979 and 1990 before returning as president 11 years ago, had kept power by maintaining leftist rhetoric while ensuring an accommodation with powerful private industry and keeping up trade with the United States.
But demonstrators have voiced frustration over corruption, the autocratic style of Ortega and Murillo, limited options to change the country's politics in elections, and the president's control over Congress, the courts, the military and the electoral board.
The Organization of American States has called for Ortega to call early elections, an issue which became the biggest stumbling block in dialogue.
Foreign Minister Denis Moncada said an early ballot would mean "dismantling constitutional order and the democratically elected government."
The demonstrations began in April as protests against social security reforms but have expanded into calls for the Sandinista president to step down.
Before protests broke out, an OAS team had been trying to mediate in a process aimed at bringing about new elections, as well as electoral reforms.
Ortega and Murillo were elected in November 2016 for a term that ends in January 2022.