Narcotics and hypotension, whats the real story?

morphine_vs_fentanyl In the critical care field, we frequently deal with patients requiring large amounts of opioid narcotics and benzodiazepines for pain management and sedation.  I’m hoping to clear up some ‘false doctrine’ that I’ve seen far to frequently.  So, narcotics and hypotension, what is the real story?

Historically, Morphine has been the go-to drug for initial pain management.  In recent years Fentanyl has founds it’s own niche.  Diazepam, midazolam and lorazepam have served as valuable adjuvants as well, but those are stories for another day.  Let’s start with morphine, or as my friends in Atlanta would say mo-phine. 

MORPHINE, the facts:
Class: Opioid narcotic
Indications: Moderate to severe pain
Dose: 3-5 mg q 3-5 minutes until pain ‘relief’ as occurred
Contraindications: hypersensitivity, known or suspected paralytic ileus 
Relative contraindications: Heart failure due to chronic lung disease, cardiac arrhythmias; increased intracranial pressure, head injuries, brain tumors; acute alcoholism, deliriums tremens; seizure disorders; use during labor when a premature birth is anticipated
Precautions: CNS depression, hypotension, respiratory depression, phenanthrene sensitivity
Adverse Effects: (>10%) bradycardia, hypotension, drowsiness, confusion, constipation, nausea, pain at injection site, respiratory depression, (<10%) histamine release
Duration: ~4 hours

What does all this mean?  In short, it means that morphine, if used recklessly, can cause some nasty side-effects.  One in ten patients you give morphine to will experience hypotension–which could be a major problem for someone who’s circulatory status is already tenuous.  Morphine also has a bad history of causing moderate histamine releases.  Remember what histamine does?  It’s that stuff that causes the domino’s to fall in the body’s inflammatory response (an anaphylactic reaction)…something no one wants to deal with in the back of an ambulance.  In addition, histamine is the guilty offender for the hypotensive properties of morphine.  Despite it’s ‘side effects’ it still has a place.  That place, is generally behind other narcotics–due to shortage or other contraindication.

Let’s talk about FENTANYL.  Here’s the skinny:
Class: Opioid narcotic
Indications: Moderate to severe pain
Dose: 0.5 – 1 mcg/kg q 3-5 minutes until pain ‘relief’ as occurred  (usually 50-100 mcg)
Contraindications: hypersensitivity
Precautions: CNS depression, respiratory depression
Adverse Effects: (>10%) bradycardia, drowsiness, confusion, constipation, muscle rigidity, respiratory depression, nausea (<10%) hypertension, hypotension, sinus tachycardia
Duration: 30-60 minutes

I’ve heard several folks say “be careful with that Fentanyl, we don’t want to drop the patients blood pressure.”  I can tell a lot about a person who says something like that.  Why do people say that?  I think it comes from two things:  (one) the individual superimposing their morphine knowledge and history with it’s inferior properties with the superior properties of fentanyl, essentially getting the two confused or (two) they frequently see a drop in blood pressure with fentanyl.   Why might we see a drop in blood pressure with administration of fentanyl?  Pain hurts.  No one likes it, not even the body.  It’s our bodies way of telling us there is something wrong.  As a result, the body get’s all amped up with the neurotransmitter epinephrine (adrenalin).  This causes an intrinsic rise in blood pressure and heart rate.  So when we give fentanyl (or any other pain medication for that matter), as the body relaxes secondary to the pain relief, we might likely see a small drop in blood pressure–nothing to be alarmed about.  So quit with the dramatic act, if your patient is in pain, give them what they need–adequate pain control.  I recently saw someone give a hypertensive 200 pound femur fracture patient 25 mcg of fentanyl because they were concerned about ‘dropping the blood pressure.’  Right…

In the early 1980’s, Dr. Carl Rosow commissioned a study analyzing the histamine release between fentanyl and morphine.  Rosow postulated that  histamine, as the major contributing factor to hypotension secondary to narcotic administration, was was worse in morphine than fentanyl.  The results of the study showed that morphine caused a 750% increase in histamine vs. fentanyl, which showed no measurable increase in plasma histamine concentrations.  We are getting closer to having a winner.  

Anecdotal and scientific evidence both support fentanyl causing far less episodes of nausea than morphine, so I’m not even going to go into detail on this one.  I hate puke.  Enough said.

 The quantity of substance required to treat pain is far different between morphine and fentanyl.  Some will chide me for comparing the amount of drug required to achieve analgesia between morphine and fentanyl, because we are comparing apples to oranges.  Even I, myself, have been critical of those who have drawn silly conclusions between the two.  Recently, however, I’ve thought that any time we can achieve the same result with introducing less of a foreign substance in the body, my instincts tell me that would be preferable.  To that end, if we can achieve greater pain control by administering 100 micrograms of fentanyl vs. 1o,000 micrograms of morphine, I think that would be better–but hey, thats just me.  

The take home message:  fentanyl is a far better drug for prehospital analgesia than morphine.  I’ve made a little chart here to outline the differences between the two: 


Note: the formulary references in this article reference morphine and fentanyl administered only via the intravenous route.  As with everything you read online, follow your local protocol.  If, however, your local protocol sucks, maybe this article could help be a catalyst for change!


Brown, Kathleen M., Jon Mark Hirshon, Richard Alcorta, Tasmeen S. Weik, Ben Lawner, Shiu Ho, and Joseph L. Wright. “The Implementation and Evaluation of an Evidence-Based Statewide Prehospital Pain Management Protocol Developed Using the National Prehospital Evidence-Based Guideline Model Process for Emergency Medical Services.” Prehospital Emergency Care 18, no. Supplement 1 (October 17, 2013): 45–51. doi:10.3109/10903127.2013.831510.
“Fentanyl: Drug Information.” Accessed June 16, 2014.
Gausche-Hill, Marianne, Kathleen M. Brown, Zoë J. Oliver, Comilla Sasson, Peter S. Dayan, Nicholas M. Eschmann, Tasmeen S. Weik, et al. “An Evidence-Based Guideline for Prehospital Analgesia in Trauma.” Prehospital Emergency Care 18, no. Supplement 1 (November 26, 2013): 25–34. doi:10.3109/10903127.2013.844873.
“Histamine Release during Morphine and Fentanyl Anesthesia. : Anesthesiology.” Accessed June 16, 2014.
Lvovschi, Virginie, Frédéric Aubrun, Pascale Bonnet, Anna Bouchara, Mouhssine Bendahou, Béatrice Humbert, Pierre Hausfater, and Bruno Riou.
“Intravenous Morphine Titration to Treat Severe Pain in the ED.” The American Journal of Emergency Medicine 26, no. 6 (July 2008): 676–82. doi:10.1016/j.ajem.2007.10.025.
“Morphine Sulfate: Drug Information.” Accessed June 16, 2014.
“Pharmacologic Agents for Pediatric Procedural Sedation outside of the Operating Room.” Accessed June 16, 2014.
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One Response to Narcotics and hypotension, whats the real story?

  1. kdkdkd says:

    1. Fentanyl attenuates M3 receptor-mediated acetylcholine-induced vasorelaxation; although the exact mechanism how is unknown, it occurs at a level before nitric oxide synthase is activated.
    2. Inhibit the vasomotor center in brainstem – vasodilation
    3. Inhibit compensatory baroreflexes
    4. (with morphine) Increase histamine release

    Obviously clinical application is most important. However “relieved pain” being the only cause for hypotension or morphine histamine release only is misguided. Even fully anesthetized isoelectric EEG patients will show a drop in blood pressure with additional opioid administration, which is clearly not due to “pain”.

    The comment, “I can tell a lot about a person who says something like that” is quite revealing. It just shows the importance of humility in medicine. Seems we can tell a lot about the author and how they treat others by that comment.

    Overall the point remains the same, clinical application is most important. A hypertensive patient crying in pain is one thing, a patient intubated sedated and maxed on multiple pressors is another story. Especially bolus dosing.

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