This story is part of a partnership between MedPage Today and VICE News.
Pop icon Prince died unexpectedly on April 21 at his home in Minnesota, a week after his plane made an emergency landing in Illinois, and rumors have been swirling ever since about what exactly happened to him. Although Prince's reps have blamed a nasty case of the flu, several reports have claimed that prescription painkillers played a major role in both the landing and the 57-year-old artist's untimely demise.
The tabloid site TMZ, which broke the news of Prince's death, reported that the landing was the result the artist overdosing on Percocet, a drug that contains the common painkiller acetaminophen and the opioid oxycodone. Citing "multiple sources," TMZ reported that Prince was rushed to a hospital and doctors gave him a "save shot," likely a reference to the drug naloxone, which is administered to counteract the effects of an opioid overdose. The day after the incident, however, Prince was apparently feeling well enough to visit a local record store and host a dance party at his home.
Airport control tower audio recordings released this week include communication about an unnamed "unresponsive" person on board Prince's jet, but don't say what caused the incident. Multiple news outlets, including TMZ, have also reported that prescription painkillers were found in Prince's possession and in his house when his body was discovered, though there's no official word on whether these played a role in his death. According to multiple reports citing federal law enforcement sources, agents from the Drug Enforcement Administration (DEA) have been called in to help investigate.
But while suspicion has focused on painkillers, a flu death isn't entirely out of the question.
Between 3,000 and 49,000 Americans die of the flu each year (the death toll varies depending on the strain of the flu that circulates in any given year), according to the Centers for Disease Control and Prevention. Even though most people who die from the flu are very young, elderly, or have compromised immune systems, the virus can kill even healthy people, said epidemiologist Dr. William Schaffner, chair of preventive medicine at Vanderbilt University Medical Center in Nashville, Tennessee.
"Flu clearly is a very, very serious infection," Schaffner said. "We know it does cause more than cough, bronchitis, fever and chills. It makes you feel so weak and bad, you have to take to your bed. It evokes an inflammatory response that the whole body is involved in."
The doctor explained that flu "kills in basically two ways." The first is that the virus can spread to the lungs and cause viral pneumonia. It can cause meningitis (inflammation of the membranes covering the brain and spinal cord) or encephalitis (inflammation of the brain), and it can also cause inflammation of the heart muscle, a condition known as miocarditis. All of these can be fatal.
The second way that flu can turn deadly, he said, is that the virus can busy the immune system so much that naturally occurring bacteria in the throat can grow out of control, causing bacterial pneumonia, which is far more common than viral pneumonia. Prince reportedly had "walking pneumonia," a nonmedical term sometimes used to describe a mild case of the illness.
Although parents bring flu-riddled children in to see the doctor quickly, adults often wait four or five days to see the doctor when they get sick, opting to "tough it out," Schaffner said. Such delays allow the illness to worsen.
"Deep trouble is when you're having difficulty breathing, coughing up stuff that actually looks yellow or green. You have a high fever and chills and feel awful," he said. "That's a bad circumstance. You need to see somebody."
Although reports about Prince and painkillers are rumors at this point, Schaffner said certain painkillers can actually worsen the flu. Codeine was once used regularly as a cough suppressant because painkillers like it tell the brain and body it doesn't need to cough. But that can actually lead to these more serious flu complications.
"If you suppress a cough, you're less likely to get bad gunk out," Schaffner said. "It sits down in bronchial tubes and predisposes you to pneumonia."
Dr. Robert Glatter, speaking on behalf of the American College of Emergency Physicians, said the flu can also trigger a deadly immune reaction known to occur in healthy people called "cytokine storm," in which the immune system goes into overdrive, causing the blood pressure to drop. It usually takes place within a matter of hours.
But as an emergency room physician, he's seen his share of opioid-related deaths, too. Drugs like Percocet suppress the central nervous system, slowing breathing and the brain stem's response to carbon dioxide.
"Someone using the medication can basically stop breathing," Glatter said. "Combine that with alcohol and benzodiazepines [a class of drugs that includes anxiety medications like Xanax]. And you're in for a problem."
Though Prince had a reputation has a wild partier during the 1980s, people close to him, including his attorney and former personal bodyguard, have insisted that he did not drink or abuse drugs. The musician, perhaps best known for the hit album and film Purple Rain, became a devout Jehovah's Witness later in life, a religion that strongly discourages overindulgence in alcohol.
But others, including Prince's former fiancé and musical collaborator Sheila E., have also said Prince was "in pain all the time" as a result of hip and knee injuries he sustained after jumping off of stage risers in high-heeled boots. Celebrity news outlet Entertainment Tonight cited an unnamed source as saying Prince "had a problem" with Percocet, which he reportedly began taking after he underwent hip replacement surgery in 2010.
Glatter said that even sleeping pills and Benadryl can worsen the dangerous effects of opiates, and noted that doctors and patients need to have frank conversations about opioid risks and the need for withdrawal-offsetting drugs and support in the event that the patient becomes addicted.
"It's one of the things that in the back of my mind — when I see a chart and it says overdose and opiates — I always consider polypharmacy," he said, referring to the term used to describe cases where a patient has used more than one drug at a time.
In January, the CDC announced that the US is in the midst of a drug overdose death epidemic. According to the latest data from the Substance Abuse and Mental Health Services Administration, 1.9 million Americans have a substance abuse disorder that involves prescription painkillers. Between 2013 and 2014, prescription opioid deaths increased by 16 percent to 18,893 deaths that year.
"I think many people are surprised," he said. "They just don't understand how dangerous these medications are. The fact that it's a prescription, they think it's safe, and that's really a misconception that patients have."
The Midwest Medical Examiner's Office in Minnesota conducted an autopsy on Prince the day after his body was discovered, but the results were inconclusive. A full report, which would include toxicology testing, could "likely take weeks," according to a press release from the medical examiner.
Follow Sydney Lupkin on Twitter: @slupkin