The death of a second victim after this weekend’s suspected fentanyl overdose involving five people in a Waikiki hotel room highlights the dangers of this synthetic opioid drug, which is driving an overdose crisis deadlier than any the U.S. has ever seen.

Honolulu Police Department officials said they have opened up a second unattended death investigation after a 53-year-old man was pronounced dead after being taken to a hospital Sunday, HPD spokesperson Michelle Yu said. Police officers and Honolulu Emergency Medical Services paramedics responded to a call at Outrigger Reef Waikiki Beach Resort at about 6:30 a.m. Sunday regarding a possible overdose case with multiple victims.

They found five victims, a 44-year-old man who was pronounced dead at the scene; two men, ages 40 and 53, who were treated and taken in critical condition to a hospital; and two women, ages 53 and 47, who were transported in serious condition. The 53-year-old man died later that afternoon at the hospital, Yu confirmed today.

HPD said it has been confirmed that fentanyl was detected at the scene.

EMS said its personnel assisted with the death pronouncement of a 44-year-old man at the hotel. The time of the first unattended death is estimated at about midnight, according to the HPD Criminal Investigation Division.

“The investigations are continuing and autopsies for both males are pending at this time,” Yu said in an email. “Anyone who has information about this case should contact HPD or CrimeStoppers Honolulu.”

Officials familiar with the case said they are looking at fentanyl as the probable cause of the death and illnesses.

Outrigger spokesperson Monica Salter said the case is an active investigation and that the resort is working with authorities. She said the resort is not permitted to share guest information due to its privacy policy.

Fentanyl, a Schedule II controlled substance, has legitimate medical uses. However, since 2020 it’s been responsible for about two-thirds of the more than 100,000 drug overdose deaths a year nationally. The nationwide total of drug overdose deaths is now about 10 times higher than drug deaths in 1988, at the height of the crack epidemic.

Fentanyl mostly arrives in the United States from Mexico and is mixed into supplies of other drugs, including cocaine, heroin, methamphetamine and counterfeit oxycodone pills. Some users seek it out. Others don’t know they’re taking it.

Ingesting 2 milligrams of fentanyl can be fatal, meaning one gram could contain 500 lethal doses.

That’s driving lawmakers across the country to crack down with harsh penalties, along with adopting measures such as legalizing materials to test drug supplies for fentanyl and distributing naloxone, a drug that can reverse overdoses.

Senate Bill 671, which decriminalizes fentanyl test strips, was passed by the state Legislature this session and was sent to Gov. Josh Green on April 18. Green was not immediately available to provide a comment on his intentions regarding the bill or his thoughts on the dangers of fentanyl to the community.

State Rep. Adrian Tam (D- Waikiki-Ala Moana- Kakaako) said he supported several measures this session that were put forth to combat the opioid crisis, including the passage of Senate Bill 671.

“It is our hope that the governor will sign this bill, as it seeks to decriminalize fentanyl test strips,” Tam said. “This crucial step enables us to address substance use disorders as a matter of public health rather than as a crime.”

“The officials’ identification of fentanyl as a potential cause deeply concerns me, highlighting the national opioid epidemic that has already claimed the lives of hundreds of thousands,” Tam said. “Moreover, the alarming surge in opioid-related overdoses within Hawaii is a pressing issue that demands our immediate attention. It is imperative that we confront this crisis with utmost seriousness to safeguard the safety and well-being of our community.”

Tam said that’s why he also supports Bill 28, introduced by Honolulu City Council member Tyler Dos Santos-Tam, which will require nightclubs and other high-risk venues to maintain doses of naloxone spray in case of an opioid overdose.

Dos Santos-Tam said in a text, “What happened in Waikiki is a tragedy. It serves as another reminder that we need to use every tool at our disposal to prevent overdoses. Narcan is one of those tools.” Narcan is the brand name for naloxone.

He added, “Bill 28 is about keeping the public safe. It’s about taking action on this horrible epidemic.”

Fentanyl isn’t just a big-city Honolulu problem. It’s a growing concern across the Hawaiian Islands, and in May the Hawaii Police Department become the first police department across the counties to release fentanyl statistics as part of its community outreach about the dangers of fentanyl. Statistics showed that during the first four months of this year, Hawaii Police Department officers made 22 fentanyl arrests and recovered 383.02 grams of fentanyl and 598 fentanyl pills.

Hawaii Police Chief Benjamin Moszkowicz said in a statement, “By proactively issuing monthly statistics on fentanyl arrests and the amount of fentanyl recovered, Big Island residents can monitor the department’s commitment to eradicating this drug from our communities. What’s more, people can keep track of accurate data themselves, rather than relying on rumors or potentially misleading claims.”

According to the Hawaii Police Department, “In recent years the use of illicit fentanyl has reached epidemic proportions on the mainland and Hawaii. Criminal drug networks are mixing this dangerous synthetic opioid into illegal counterfeit pills and selling them as legitimate prescription pills, often with deadly consequences.”

Hawaii Police Department Detective Jesse Kerr, of the department’s Area I Vice Section, said in a statement, “This drug is way more dangerous than anything else we’ve encountered in recent years.”

Hawaii police said one of the factors making illicit fentanyl so dangerous is that it is 50 times more deadly than heroin. Plus, they said, just a tiny amount of fentanyl, as little as 2 milligrams (about one grain of Hawaiian salt) can be fatal in a non-opioid- tolerant person.

Hawaii police also said drug traffickers are disguising fentanyl as legitimate prescription pills, such as Adderall, Xanax and OxyContin, or pressing it in colored pill form such as rainbow fentanyl.

“We used to see blue- colored pills, and now we’re seeing fentanyl pills in all different colors as the drug traffickers try to elude law enforcement,” Kerr said.

Hawaii Police Capt. Thomas Shopay of the department’s Area II Criminal Investigation Division added in a statement, “The risk is that people might unintentionally ingest something not realizing it may contain fentanyl. People of all ages should always make sure they know the origin of the medication they take and to not take pills from unknown sources, even if they come from friends.”

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The Associated Press contributed to this story.