Ralph Battels figured it out when one of his patients woke up and tried to punch him in the face. A single shot of naloxone often really isn’t enough to do the trick anymore.

Addicts in the Colorado town where he’s an emergency room doctor are downing such incredibly powerful opioids that the overdose-reversal agent may have to be applied two or three times -- or more -- to revive them and calm their sometimes violent highs. The budget at Pagosa Springs Medical Center is taking an unanticipated hit, another victim of a raging national epidemic.

“It’s a problem that frankly we should be able to control,” Battels said. “But it’s a big challenge. It’s everywhere.”

Hospitals and emergency-services agencies across the U.S. are confronting higher bills for the chemical compound that can block the effects of painkillers and heroin, as super-strong synthetic opioids like fentanyl and carfentanil grow increasingly popular. Not only are more doses of the remedy often required, prices for some brands of naloxone have been ticking up.

“You try and balance product cost and care -- and that creates obvious problems,” said Nilay Shah, a consultant in the Division of Health Care Policy and Research at the Mayo Clinic and one of the authors of a study published in the New England Journal of Medicine that warned escalating costs threaten efforts to save lives.

The number of naloxone recipients getting multiple doses has grown more than 25 percent since 2012, according to research published in May by the National Association of EMS Physicians. Some medical centers have increased their routine doses just to be safe, with Danbury Hospital in Connecticut, for example, now giving four-milligram rather than two-milligram applications of Adapt Pharma Inc.’s Narcan as a matter of course. Some can’t keep up: St. Vincent Hospital in Leadville, Colorado, recently ran out and had to borrow supplies from a nearby facility.

Legally Bound

It all adds up to a drain on health-care resources. In Florida, the Manatee County Emergency Medical Services department gave 432 applications of naloxone in June compared to just nine in the same month four years ago, with a 650 percent cost increase to $109,650.

“We have noticed an ebb and flow of different synthetics, some requiring multiple doses to bring patients around,” said Paul DiCicco, the department’s chief. The synthesized opioids, often manufactured illegally and available over the internet, can be dozens of times stronger than heroin.

EMS crews save money by stocking the cheapest naloxone available and buying low-cost nasal dispensers instead of purchasing the medication in pre-filled injectors. But they’re legally, and ethically, bound to try to save lives no matter the cost.

“There’s no way not to respond to a 911 call,” said Brent Myers, president of the National Association of EMS Physicians. “And once there, there’s no way not provide a life-saving treatment.”

A city councilman in Middletown, Ohio, proposed doing just that earlier this year -- with a baseball-style strike-out rule where emergency response personnel wouldn’t be dispatched to someone overdosing for a third time.

Nine Doses

“We need to put a fear about overdosing in Middletown,” the councilman, Dan Picard, told his colleagues when he made his suggestion, which he quickly withdrew upon realizing the legal hurdles it faced.

There are about 50,000 people in Middletown, and there have been around 600 overdoses so far there this year, more than in all of 2016. And because the opiates are getting so much stronger, it can take up to nine doses of naloxone to revive a person, according to a report prepared by the city manager.

President Donald Trump has backed a recommendation in a report from the President’s Commission on Combating Drug Addiction and the Opioid Crisis and said the epidemic is a national emergency. Declaring an emergency, the report said, will allow Department of Health and Human Services Secretary Tom Price to negotiate reduced pricing for government-issued naloxone.

The federal government and many cities and states have moved to make naloxone, first approved by the Food and Drug Administration in 1971, more easily available. It can be purchased over the counter in about 40 states.

Annual sales of all brands went from $21.3 million in 2011 to $81.9 million in 2015, according to QuintilesIMS Holdings Inc., which tracks drug sales. The brand that has gotten the most attention and criticism is Evzio from Kaleo Inc., an injectible that’s made for personal use and not widely used by hospitals or EMS crews. The two-dose package list price went from $690 in 2014 to $4,500 last year, according to research published in December in The New England Journal of Medicine. Kaleo said it did that to generate more revenue to expand its patient-assistance program, which covers insured individuals’ co-payments and most costs for low-income people.

Manufacturers such as  Amphastar Pharmaceuticals Inc. and Hospira Inc. offer discounts and rebates and negotiate with hospitals and others, so that few buyers actually pay the list price, with out-of-pocket costs for people with insurance usually much less. Many companies, including Kaleo, donate batches of their products to public-health, emergency-services and nonprofit agencies.

The epidemic has reached critical proportions, said Gail D’Onofrio, chair of the emergency medicine department at the Yale School of Medicine. With overdose rates up and opioids more powerful, “it’s a perfect storm.”

This article was provided by Bloomberg News.