Expert: Dr.Paul Skett - 10/19/2008

Question
QUESTION: First, I hope you might help me understand something about oral vs. parenthal dosing of morphine ... and something about the half-life, I suppose.  I am trying to understand how much morphine you might suspect was in his system at the end ...

Prior to the final hospitalization, he took 3x30mg tablets twice a day of ms contin (time release morphine) for arthritis pain.  A head injury landed him in the ICU.  He was conscious but on a vent.  Except for paralytic in the beginning, he was not given any other meds for pain, and no benzos during the next nine days.

For the first 7 days, he was given 2mg/h morphine sulfate thru his IV every hour.  I was told this was "aprx the same" as the 3x30 2xday oral dose he had been taking.  It did not seem to be near enough pain relief to me but then again he also had entirely new pain issues to deal with as well and I am not a medical professional.  Would you agree he was getting about the same amount of morphine or do you think differently?  

Even though his vitals remained the same, on the seventh day, his morphine was increased from 2 to 10mg every hour through his IV.  It seemed to be a good thing for the first 24 hrs but after that he seemed to be floating but could still open his eyes.  How would this compare to his pre-hospital oral dose 3x30mg tablets twice a day and would the amount of morphine in his body INCREASE each day due to a half-life of the morphine?

After aprx 26 hrs his fever spiked and he was drench in sweat. The nurse wrote:  "probably due to the morphine".  They iced him down.  A few hours later his blood pressure crashed ...  Several hours later, during my absence, the record shows he was given a 10mg dose through the IV - every 15 minutes for 1:15 mins (5 total).   .... is there some method to estimate how much morphine was in his system at this point in time?  And do you think the morphine alone could be enough to overdose this person?

I cut some locks of his hair once it was all over ... do you know if there might be some method to determine how much morphine he had in his system through analysis of his hair?
And if so, would one's ability to read this in a hair sample most likely diminish over time?

Hope this makes enough sense for you to respond.  You know some very interesting and important things!

Thanks.

ANSWER: Hi, Th,

Thanks for your question.

First let us look at the difference between oral and i.v. morphine. Oral time-release morphine does just what it says - it is taken by mouth and slowly releases morphine over the day. Only a proportion of the morphine taken by mouth is absorbed (depends on how taken, with what, if food in stomach etc. - so actual amount absorbed varies greatly) - also slow release means actual blood concentration is fairly low even though 180mg/day taken.

I.v. morphine goes, of course, direct into the blood and then to the brain to have its effect - all of the drug given gets there, so you know exactly how much is given. Morphine is then titrated to get the pain-killing effect required.

2mg/hr = 48mg/day - a reasonable approximation to the 180mg/day taken orally. The increase in dose was probably because, as you say, the effect did not seem good enough and, probably, your husband was tolerant to morphine having taken it for a while. So up the dose to 10mg/hr - the "floating" effect is expected at a higher dose of morphine (and, indeed, shows that a good dose is being used - morphine does not get rid of pain but changes the perception of the pain). Dose now 240mg/day i.v. which is more than the oral dose but within guidelines.

Morphine has a short half-life - thus, the need for slow release or continuous i.v. use so little likelihood of build-up in the body.

Higher doses of morphine can cause hyperthermia (high body temperature) and low blood pressure but this has to be offset against the pain-killing properties required. The total of 50mg in one hour 15 minutes is high but again was there a reason for this? More analgesia required?

It is impossible to calculate the likely concentration of morphine at this time, unfortunately. It is not clear if this is an overdose or just a ramping up of the dose due to tolerance developing - addicts can tolerate a single dose of 2000mg of heroin (a stronger drug than morphine).

Hair analysis is useful to show the presence of morphine but not its concentration at any time.

Hope this information is useful to you.

Best wishes,

Paul



---------- FOLLOW-UP ----------

QUESTION: Thanks for your thorough answer.  Now I hope you might shed some light on the change in his eye color ....

This patient was on a ventilator in the ICU the 9 days.  After the 50mg morphine administration in 1:15, he was subjected to an apnea test (brain death testing) which he failed due to no spontaneous breathing.  He was then declared legally dead. All medical interventions were then discontinued.  I was there as the equipment was shut down, all lines and tubes removed (hydration and feeding).  I sat with him 1.5 hrs.  Record shows, after I left, he was put in body bag and sent to hospital morgue where his body remained for 2 weeks.

I saw his frozen corpse 2 weeks later.  In addition to slackening of jaw, growth of whiskers, discharge from nostrils, and eyes opening, I was surprised to see that his always hazel colored eyes (green/brown) were BLUE.  I made color photos and have shown them to other close friends, family members who remark, "How did he get those blue eyes?"

Can you tell me what might cause this post mortem change?

Thank you again.  You give great answers.

Answer
Hi, Th,

This must have been a pretty bad time for you. I' m sorry.

As to eye colour, there is very little in the scientific literature that can help us here - BLUE eyes are just the absence of pigment and so turning from hazel to blue is just a loss of pigment (melanin).

This may have simply degraded on storage of the body. See quote below:

Experienced forensic pathologists and examiners may be familiar with the phenomenon of postmortem iris color change; however, only Knight, Simpson's forensic medicine, Arnold, London, 1997; Ref. 1 and Saukko and Knight, Knight's forensic pathology, 3rd ed., Arnold, London, 2004; Ref. 2 have referred to it in the literature, and to date, there have been no published scientific research studies on this taphonomic artifact.

Don't think this is related to the treatment.

Best wishes,

Paul