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Something in the way endorphins won’t let me be
I don’t want to be your patient
So naloxone, won’t you set me free?

Stop playing with my heart
Finish what you start
When you make my blood pressure come down
If you want me, let me know
Baby, let it show
Naloxone, don’t you fool around

Just try to understand
(Understand)
I’ve given all I can
‘Cause you got the best of me

Borderline
Feels like I’m going to lose my BP
You just keep on pushing my BP over the borderline
Borderline
Feels like I’m going to lose my BP
You just keep on pushing my BP over the borderline

Borderline

I write the first of this draft of this entry on 8th of July for a July 18th publish date. Information may evolve, and everything you are about to read is a crock. As French manga might say, Sailor Vee.

My wife and I are at that stage in life where we read feed headlines to each other in the morning over coffee. My parents would read newspaper headlines to us, but newspapers are not what they once were.

“Madonna got naloxone,” she said. “Pulled her back from the dead.”

Say what?

Madonna was not in my feeds. I was surprised to find she was newsworthy but I am far removed from popular culture. Madonna, along with Purple Rain and She Bop, were the soundtrack of the courtship of my wife. Somehow Madonna got old. She is 64, less than a year from Medicare, and just a year younger than me. Everyone is getting old. We are going to see Neil Young Monday, which is yesterday, and he’s 77!

It is a popular pastime in Infectious Diseases to speculate on the illnesses of the rich and famous. Did Lincoln have aortic insufficiency from syphilis or was it just Marfans? Did Alexander the Great die of an amoebic liver abscess rupture? In that tradition, I will yammer on a bit about Madonna.

The details of her illness are, of course, vague. As they always are on the web. Somehow the information I would want, like the name of the bacteria, are never mentioned.

An elderly woman is found down, lifeless!, is revived, is found to have a “severe bacterial infection”, spends a few days in the ICU and is soon sent home to recover.

A very common clinical scenario, and, common things being common, I would bet on E. coli urosepsis. Infections with an easily controlled source get better very fast, and really, that would only be urosepsis. Modern ICU care snatches people back from the brink of septic death every day. Maybe Madonna had some other bacteria or infection, but there is a lack of clinical information for further pointless speculation. Hopefully, we will never know. But the damage has been done. Google News knows I have clicked on Madonna. My feeds are doomed.

It is the use of naloxone (brand name Narcan) that got my attention. Today, naloxone is primarily used to reverse the effects of narcotic overdose. It is an opioid antagonist and binds to opioid receptors to reverse the effects of opioids such as heroin. It doesn’t last long, a 30-60 minute half-life, and I have seen people revived then lapse back into methadone (8-59-hour half-life) coma over the course of a couple hours. I wonder how often those who get a dose in the community for a fentayl ( half-lives 3 to 7 hours) overdose and refuse further care wander off to die a few hours later.

Why was the naloxone given to Madonna? Again, the reports are not clear. I assume she was found down and they have her a snort (naloxone comes as a nasal spray) just in case it was an opiate overdose. The emergency tech would have no way of knowing if was an overdose or not, so safe is better than sorry.

Evidently, the naloxone was the wonder drug that worked wonders and brought her back from the borders of Tartarus.

It also brought back memories. Watching her Borderline video on MTV with my then girlfriend, now wife. The ice collecting on the windows during call nights at Hennepin County Hospital, where I met my wife to be. True story of our first meeting. I was post call, trying and failing to put a central line in a demented patient, so I called for help from a nurse. As the nurse entered the room, I hit the subclavian, passed the catheter, and I could now go home and sleep. I turned to the nurse, who I had never seen before, and said, “Thanks. You brought me good luck. Will you marry me?” The rest is history. I digress. As ususal.

And I remember giving naloxone for sepsis.

Back in the day there was a brief flurry of interest in giving naloxone as it improved blood pressure in sepsis.

When you are dying of sepsis, the body releases endogenous morphine aka endorphins that help perpetuate low blood pressure. I figure it is nature’s way of letting you die comfortably. Naloxone blocks endorphins. If you search the PubMeds for naloxone and sepsis, you will find a series of articles in the 1980s showing transient benefit from naloxone for raising blood pressure in sepsis. And, I suppose, making your death from sepsis more unpleasant. Waking up to your unexpected impending demise might transiently raise the blood pressure. Panic does that.

Naloxone had salubrious effects on a variety of parameters I spent much of my internship in the ICU measuring. I don’t think I have seen a Swan Ganz catheter in the ICU for decades.

… a moderate nonsignificant increase in cardiac index, pulmonary capillary wedge pressure, and systemic vascular resistance.

The use of naloxone was based on animal studies and care reports and we gave all our septic patients continuous infusions of naloxone. I cannot remember if it helped or not.

The use of naloxone went nowhere as although it improved blood pressure, it did not change the outcome. Patients still died at the same rates. Two placebo-controlled studies were the steak (sic) in the heart of naloxone use for sepsis.

Mean systolic blood pressure rose by 13.3% in the naloxone group and 11.3% in the placebo group. Two-way analysis of variance for repeated measures of blood pressure, obtained over 30 min periods before and after treatment, revealed no significant difference (p greater than 0.10) between treatment groups.Survival rates in the two groups at 48 h and 7 days after the start of treatment were similar. Naloxone, 0.4 to 1.2 mg intravenously, was no better than placebo in ameliorating hypotension in septic shock..

and

Five (46%) of 11 patients in the naloxone group and one (9%) of the other 11 patients in the placebo group responded clinically. The MAP among the five responders increased from 62 +/- 5 to 89 +/- 4 mm Hg within 20 min of naloxone treatment (p less than .01). This favorable hemodynamic response was sustained throughout the patients’ clinical course. In contrast, the MAP did not change significantly in the nonresponders who received naloxone, nor did it change in the placebo group. More patients in the naloxone group than in the placebo group received steroids concurrently. Survival rate was 100% in those who responded to naloxone clinically. However, overall survival rate in each group was essentially the same. No adverse effects were observed, except for mild agitation in some of the patients receiving naloxone. We conclude that naloxone infusion is clinically efficacious in improving the hemodynamic profile of a subgroup of patients with severe early hyperdynamic septic shock, but does not appear to improve the overall survival rate.

Although as house staff, we somewhat cynically said it was our job to make sure patients died with normal numbers.

Of course, no therapy every truly dies in medicine. Someone always reinvents the wheel. In 2010, nalmefene, an opiate antagonist, was used in sepsis with the same results.

Based on the conventional anti-shock therapy, early use of nalmefene can improve the hemodynamics, which is conducive to ameliorate septic shock, however, there is no significant effect on 28-day mortality.

So, is there some doc in NYC who still believes in naloxone for sepsis? The lifestyles of the rich and famous often includes more medical care than us regular folks receive, although more is not always better. I don’t think so. Naloxone for sepsis may be passe, but I do not doubt Madonna got a blood pressure boost from naloxone for worries of opiate overdose as she was heading to the hospital and it may have been of transient benefit. But it was the ICU care that saved her.

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  • Mark Crislip, MD has been a practicing Infectious Disease specialist in Portland, Oregon, from 1990 to 2023. He has been voted a US News and World Report best US doctor, best ID doctor in Portland Magazine multiple times, has multiple teaching awards and, most importantly,  the ‘Attending Most Likely To Tell It Like It Is’ by the medical residents at his hospital. His multi-media empire can be found at edgydoc.com.

Posted by Mark Crislip

Mark Crislip, MD has been a practicing Infectious Disease specialist in Portland, Oregon, from 1990 to 2023. He has been voted a US News and World Report best US doctor, best ID doctor in Portland Magazine multiple times, has multiple teaching awards and, most importantly,  the ‘Attending Most Likely To Tell It Like It Is’ by the medical residents at his hospital. His multi-media empire can be found at edgydoc.com.