Judging from the press inquiries I’ve had since 5 am EDT today, expect today’s focus in the Michael Jackson case to be on the anesthetic drug, propofol (Diprivan®).
Last evening, California nutritionist and registered nurse Ms Cherilyn Lee gave an interview to Campbell Brown on CNN (and this AP exclusive report) describing Michael Jackson’s repeated requests of her for the intravenous sedative drug for his insomnia. She wisely rejected his requests, instead providing him with a vitamin and mineral “energy” injection called Myers’ cocktail.
However, four days before Jackson’s death she reported a frantic phone call from a Jackson staffer to her that led her to believe he had somehow procured the drug or something like it:
While in Florida on June 21, Lee was contacted by a member of Jackson’s staff.
“He called and was very frantic and said, `Michael needs to see you right away.’ I said, ‘What’s wrong?’ And I could hear Michael in the background …, ‘One side of my body is hot, it’s hot, and one side of my body is cold. It’s very cold,'” Lee said.
“I said, `Tell him he needs to go the hospital. I don’t know what’s going on, but he needs to go to the hospital … right away.”
“At that point, I knew that somebody had given him something that hit the central nervous system,” she said, adding, “He was in trouble Sunday and he was crying out.”
[. . .]
“I don’t know what happened there. The only thing I can say is he was adamant about this drug [Diprivan],” Lee said.
In the photo of Ms Lee that accompanies the AP report and the video interview now at ABC News, she looks terrifically distraught and was obviously very concerned about Mr Jackson. My thoughts go out to her as I suspect she is second-guessing what she might have done differently to help him.
What is Diprivan (propofol) and how is it normally used safely?
Diprivan is the trade name for propofol (PROPE-uh-fawl), a product of AstraZeneca whose healthcare professionals website on the drug is currently closed. Estimated US annual sales of Diprivan are $375-400 million USD.
Propofol has a deceptively simple chemical structure and is known chemically as 2,6-diisopropylphenol. Its formulation in the Diprivan injectable product is as an emulsion with egg phospholipids. This imparts a white appearance that is responsible for its colloquial term amongst health professionals, “milk of amnesia.”
It is a widely-used intravenous anesthetic used primarily for outpatient surgical procedures owing to its very rapid onset of action, sometimes as fast as 30 sec, and rapid recovery. It is also used for inpatient procedures such as intubations, in conjunction with longer-acting anesthetics, and in painful procedures such as changing burn dressings.
Propofol has a remarkably good safety record given its widespread use. The average human intravenous dose is 2 to 2.5 mg per kg body weight while the intravenous LD50 (dose that is lethal to 50% of a population) in mice is 50 mg/kg. When used alone, or in combinations with the opioid analgesic fentanyl, it produces a “dissociative analgesia” that is very rarely fatal. Hence, its safety is one of the reasons it is used for outpatient surgery, together with its rapid onset and quick recovery. However, the prescribing information for Diprivan notes specifically that the dose should be reduced when the drug is used together with opioids (such as meperidine or fentanyl) or other sedatives such as benzodiazepines.
Note added: Later today, KevinMD (Dr Kevin Pho) further emphasized 1) there is no scientific basis for its unapproved indication in insomnia and that 2) propofol should never be found in a home. He goes on to say:
That is some serious malpractice, bordering on criminal, if any doctor had indeed injected Jackson with Diprivan simply to help him sleep.
While it is indeed a sedative, it has been reported to produce euphoria (the pleasant feelings of well-being most often associated with morphine and other opioids) in some people who have procured it for the purposes of clandestine use.
The potential risk is from “propofol-related infusion syndrome” – it can produce an elevation in body temperature that is usually not fatal (not “true” malignant hyperthermia as with the rare but fatal side effect of some inhaled anesthetics) but can trigger muscle breakdown called rhabdomyolysis, a rare but devastating side effect that can also occur with statin cholesterol-lowering drugs.
An excellent and timely review of propofol-related infusion syndrome was published in the May issue of Pharmacotherapy by Dr Stephanie Mallow-Corbett and colleagues from the University of Houston College of Pharmacy. The article is reprinted at Medscape (available with free registration). Most notable in this review is that while the syndrome is rare, it is fatal in 64% of cases when it does occur.
However, most relevant to the Jackson case is that propofol can cause cardiac tachyarrhythmias (rhythmic disturbances at high heart rate), especially in people predisposed to cardiac problems.
As I wrote last week in my blog post on Demerol ® (meperidine), Jackson’s reported long-term use of this analgesic for back pain may have already primed him for cardiac problems due to the accumulation of a toxic metabolite, normeperidine. However – and please note – that while all of my pharmacology/toxicology discussion is based in science and medicine, any extrapolation to the Michael Jackson case and the cause of his death is speculation at this point. I only have access to the reports regarding his potential drug exposure that all of you do. Only time will tell what is the truth once the full autopsy and toxicology reports are released.
What is Myers’ Cocktail?
Myers’ Cocktail is a vitamin and mineral supplement concocted by the late Baltimore physician, Dr John Myers, that has now been popularized by alternative medicine physican, Dr Alan Gaby. According to the abstract for Gaby’s 2002 article in Alternative Medicine Review (2002; 7:389-403; full text PDF available free at time of posting) on the concotion:
Building on the work of the late John Myers, MD, the author has used an intravenous vitamin-and-mineral formula for the treatment of a wide range of clinical conditions. The modified “Myers’ cocktail,” which consists of magnesium, calcium, B vitamins, and vitamin C, has been found to be effective against acute asthma attacks, migraines, fatigue (including chronic fatigue syndrome), fibromyalgia, acute muscle spasm, upper respiratory tract infections, chronic sinusitis, seasonal allergic rhinitis, cardiovascular disease, and other disorders. This paper presents a rationale for the therapeutic use of intravenous nutrients, reviews the relevant published clinical research, describes the author’s clinical experiences, and discusses potential side effects and precautions.
While Myers actually recipe was never published, this is the formula that Gaby uses as published in his review:
2-5 mL of magnesium chloride hexahydrate 20% (assume w/v?)
1-3 mL of calcium gluconate 10%
1 mL of hydroxocobalamin 1,000 mcg/mL (one form of vitamin B12)
1 mL of pyridoxine hydrochloride 100 mg/mL (vitamin B6)
1 mL of dexpanthenol 250 mg/mL (vitamin B5)
1 mL of “B complex 100 (B complex)” (composition not defined in Gaby paper)
4-20 mL of Vitamin C 222 mg/mL (C)
Results of a recent trial of Myers’ Cocktail (termed intravenous micronutrient therapy, or IVMT) in patients with fibromyalgia were published in the Journal of Alternative and Complementary Medicine but concluded that there was no statistically significant difference in symptoms between placebo and IVMT.
Most relevant to the Jackson case is that the safety of Myers’ Cocktail is not yet clear. I am particularly concerned with the calcium composition of this intravenous brew; while not likely to be toxic on its own, if dosed as listed, I do have some concern if Mr Jackson already had pre-existing cardiac problems and/or was receiving drugs such as Demerol (meperidine) or Diprivan (propofol) which each pose a risk of cardiac toxicity.
So, while press reports will be focusing today on Diprivan (propofol), let us not forget to consider the potential contributions of this “natural, alternative” therapy in the sad case of his death.