The Drug Enforcement Agency issued a safety guide for first responders who might come in contact with synthetic opioids due the dramatic increase in the drug’s potency and availability.

So far, no responders have been harmed, said Ken Solek, the DEA’s assistant special agent in charge for Minnesota. But several police officers and investigators around the United States nearly died from just a small amount of exposure to the opioids.

A Star Tribune analysis of state death certificate data found 402 opioid-related deaths in 2016, up from 344 in 2015. Deaths related to synthetic opioids doubled from 50 in 2015 to 101 in 2016. Prince died from an accidental overdose of fentanyl a year ago.

That trend appears to be continuing, given the recent announcement by the Hennepin County medical examiner of 11 deaths so far this year from a new synthetic known as carfentanil. Minnesota has seen a larger influx of the drug than most other states.

Used legally as a tranquilizer in large game animals, carfentanil is considerably more potent than other opioids. Like fentanyl, it also appears to be compounded into illicit doses of heroin because it is cheaper for drug dealers to make, transport and sell — making street drugs far more dangerous.

The 19-page briefing warns that there is a significant threat for law enforcement, jail intake and emergency room personnel and first responders who come in contact with the synthetic opioid fentanyl, which is 50 to 100 times more potent than morphine. Since fentanyl can be ingested orally, inhaled through the nose or mouth or absorbed through the skin or eyes, any substance suspected to contain fentanyl should be treated with extreme caution.

The warning said a small amount could lead to significant health-related complications or death.

According to the DEA briefing, opioids continue to be the most significant contributor to overdose deaths in the United States. The Centers for Disease Control and Prevention reported 33,091 opioid deaths in 2015, one-third caused by synthetic opioids. In 2014, the DEA created a heroin-fentanyl task force to “facilitate a whole government approach” to the opioid epidemic.

The briefing goes into detail about the variations of synthetic opioids, including powder, pill, capsule, liquid and on blotter paper. Accidental exposure can happen during execution of search or arrest warrants, purchase of fentanyl during undercover operations or processing of non-drug evidence such as drug proceeds or scales. It can also harm drug-sniffing police dogs.

The briefing also gives recommendations for the safe handling of synthetic opioids and what to do if exposed to the drugs. Many local agencies are training their employees about the risks, and they keep the opioid antidote naloxone on hand just in case.