The Basics of Vasopressors
There is a ton to speak about regarding vasopressors, but before we get to the edge cases, we need to set-up a foundation.
Types of Shock
- Obstructive
- Hypovolemic
- Cardiogenic
- Distributive
It's all about flow!
- Should we get rid of blood pressure?
Critical Perfusion Pressures
- CV Collapse 35 mm HG (51 mm Hg in critical AS pts) in one study (Crit Care 2014;18:719)
- SBP < 80 or DBP < 50 lead to trop rise during post-partum hemorrhage (Anesthesiology 2004;100(1):
30–6) - MAP of 50 in non-vasculopath dogs for the brain? [cite source='pubmed']9692450[/cite] and Blood Pressure and the Brain: How Low Can You Go? [Anesth Analg 2019;128(4):759]
- MAP of 65 for the heart? (Dunser et al. think it is 45-50 for the heart)
- MAP 65-75 for the Kidneys? [cite source='pubmed']18382191[/cite]
- Paper on the BP Associated with Terminal Collapse
- Systolic of 47 and MAP 35
When we put someone on a vasopressor, what are we hoping to accomplish?
- Critical Perfusion Pressures (Heart will get better, but may look worse)
- Increase Venous Return-Unstressed to stressed volume
- Avoid Gut Ischemia and Flow Reduction
Norepi Increases Venous Return as well as Constricting Afterload
- Crit Care Med. 2012;40(12):3146-3153
- Crit Care Med. 2011 Apr;39(4):689-94
- Crit Care Med. 2013 Jan;41(1):143-50
- Critical Care 2007, 11(Suppl 2):P37
- Critical Care 2010, 14:R142
- Anesthesiology 2014; 120:365–77
- Want to understand the physiology of venous return?
MAP of 65 or Higher?
No benefit to 80-85 group [cite source='pubmed']24635770[/cite]
The 65-Trial may indicate that 60 is as good as 65
Vasopressor Flow Chart
Update: The Hinds Perspective
Various Vasopressors
Terminology
- ‘pressors/catecholamines/inotropes are not so helpful
- Pure Pressors
- Inopressors
- Inodilators (another show)
Why Norepi?
[cite source='pubmed']10966247[/cite]
Should become weight based
Should tolerate tiny doses
Why Not Dopamine?
'cause it is crappy
Vasopressin
Phenylephrine
Epinephrine
Effects on Mortality
Early norepi was better than later norepi [cite source='pubmed']25277635[/cite], [cite source='pubmed']25072761[/cite]
Up and Coming Vasopressors to be Discussed in Future Episodes
Methylene Blue
Angiotensin II
Peripheral Vasopressors
Very Good Review Article on the Effects of Vasoactive Agents on Microcirculation
Great Review [cite source='pubmed']20811874[/cite]
Review Articles
- [cite source='pubmed']12386503[/cite]
- [cite source='pubmed']21097695[/cite]
- Moving beyond BP cosmetics by Dunser
- Excellent Physio Review by Kenny
Understanding Venous Return
[cite source='pubmed']24966066[/cite]
Must Read Posts By Josh Farkas
- Early MAP Stabilization
- Renoresuscitation 12/2014
- Vasopressin & renal function 12/2014
- VANISH trial & vepinephrine 8/2016
Additional New Information
More on EMCrit
- Early norepinephrine to stabilize MAP in septic shock(Opens in a new browser tab)
- PulmCrit- Epinephrine challenge in sepsis: An empiric approach to catecholamines(Opens in a new browser tab)
Additional Resources
Editor-in-Chief, at EMCrit.org
An ED Intensivist from NY.
Professor
Nassau University Medical Center
No conflicts of interest (coi).
Professor
Nassau University Medical Center
No conflicts of interest (coi).
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Scott,
For weight based norepi, do you use .04-.4 mcg/kg min?
prob more like
0.01 – 1 mcg/kg/min
Awesome intro to the topic!! I have a lot of reading up on vasopressin to do, it seems. You mentioned not knowing about the mortality rate of norepi vs. dopamine in the podcast….have you seen this from a couple of years ago? http://www.ncbi.nlm.nih.gov/pubmed/20200382
Again, thanks for making this….I need to spread it around to my coworkers to get them weaned off of the dopamine 🙂
yes, Ben–that is the study that established how annoying dopamine is in regards to a. fib and other issues. No mortality difference in that one though.
Hi Scott, It seems the Australians and the RAGE guys are a bit anti phenylephrine (and I’ve just seen just seen John Hinds tweet with your “modified” algorithm!) in the CC/resuscitation setting. I use it a lot in my anaesthetic practice and I think it’s a good drug in that context. What are the issues with it in CC/resus? Tachyphylaxis? Lack of evidence base? On a slightly unrelated I recently listened to your podcast about haemodynamic monitoring/targeting for doses of epi in cardiac arrest. You mention the alpha effects of epi are good in that situation but the beta effects… Read more »
Phenylephrine will increase SVR and BP but decr cardiac output, maybe that’s why?
I hate Phenylephrine. HATE IT. It is a reasonable drug for patients who are young, fit, well, hyperdynamic, filled and vasodilated – i.e. Pregnant ladies having spinal anaesthesia for elective c-section. It is also quite a reasonable drug for occasional use in fit, well, elective anaesthesia cases. For critically ill patients, it is garbage. Why pick an agent with variable effects in different states of (unquantifiable) preload dependence, but which can be pretty well relied on to merely increase after load at the expense of cardiac output if you’re sick? There’s only three reasons I can see that people use… Read more »
I love phenylephrine. Just had to say it, John. In all honesty though. I use it at times in the ICU in “sick” folks. I guess you have to define sick in order to argue against phenyl use in certain patients. Couple advantages I have come to see in the drug is it is spectacular for the anesthesia induced hypotension after an elective or semi elective intubation in the ICU setting. The ever stressful drop in MAP may not change mortality but I am not sure that 15 to 20 minutes of pretty severe hypotension is a good thing. Pushing… Read more »
Hi Craig;
Thanks for joining in on the discussion; always good to hear what others are up to
I have to say, if I was frequently getting “15 – 20 minutes of pretty severe hypotension”, following an “elective or semi-elective intubation in the ICU setting”, I’d be having a good, hard look at my Units practice
Likewise, if it was taking an hour to get Noradrenaline from the pharmacy, I’d be looking to fire someone!
That’s an absolutely crazy situation
-John
Goodness John. I seemed to have unleashed the lion in you…. 😉 Well I guess we are getting a bit off topic about phenyl and you have seemed to question the variance of common practice scenarios. So from one lion to another……. I don’t know your background so I will not assume the scenarios you practice in. Heeeeeeeheeeeee just kidding! My approach to patient care is typically not at all dogmatic. I will point out a few facts regarding what I have seen in the 18 hospitals since fellowship I have worked in spanning through Oregon, Washington, South and North… Read more »
mephentine is the go to drug in India in these cases
John, there is no reason to hold back on emcrit. please tell us how you really feel.
: )
s
Scott, for MAP of 65 are you getting that MAP number from an arterial line or from (NIBP) non invasive BP monitor ?
From your clinical experience, how close are NIBP measurements to A line BP numbers?
Thanks
Personally in the ICU I find that the maps sometime correlate very well as long as the cuff can find a pressure. My understanding is the the non invasive cuffs have some issues….note the link.
Overall though I find that the cuffs usually underestimate the invasive systolic and diastolic pressures. The maps tend to be more accurate.
http://hyper.ahajournals.org/content/35/5/1032.full
Agree with Craig, NIBP MAP is pretty good until the patient is pretty bad (MAP<50 or so).
No mention of ephedrine — bolus dosing for transient hypoTN (ie post-intubation, sedation, etc).
Some evidence that maybe it might be a better choice than Phenylephrine –http://www.ncbi.nlm.nih.gov/pubmed/22046862
Of note, I have pre-made phenylephrine and ephedrine — haven’t been able to get pre-made epi yet.
ephedrine is an very, very long halflife drug for a vasoactive. overshoot with this one is a bitch
So would you use the phenyl or ephedrine if you had to choose (ie those no push dose epi in site at my institution–but I can get a bag made in about 5min by our great pharmacists so maybe I’ll start asking for that upfront and bolus dose from that)? I have had great antidotal experience with ephedrine at about 1-2.5mg to get BP and HR — I’ll keep in mind the overshoot. Thanks for the responses and the great stuff you put on weekly — big fan since the beginning. Keep it coming.
Matt
Couple other questions:
1. Do you have the fixed dose VPN literature vs titrating the dose (ie if literature even exists)?
2. Do you know if there is literature to show at approximately/ballpark dose epinephrine lactate product begins to overcome the body’s ability to metabolism it ie at what dose does lactic acidosis begin to occur??
Thanks
Matt
U of Wisconsin CCM fellow
1. dose exist. easiest way to find all the refs is to go to SSC guidelines; they have the biblio there.
2. have not seen dose dependent epi/studies; but for reference, dosing of epi as inotrope in STC CSICU is 0.01-0.08 mcg/kg/min and at this range, rarely saw hyperlactatemia.
Several of the neuro intensivist lecturers (don’t shoot me if this is Dogma and I’m ignorant to studies that are out there) I’ve been to recently have said that they absolutely love phenylephrine in neurogenic shock patients refractory to norepinephrine.
Any thoughts ?
Paul Tank – Medic
AirMed – Michigan
These are (otherwise) young, fit, healthy, filled, hyperdynamic but vasodilated patients – Phenylephrine is a good choice if they are Norad unresponsive
(Assuming they are an isolated spinal injury, and not a polytrauma)
-John
John, Where are these young fit healthy patients you speak of in the non trauma ICU. Jesus man I have not taken care of one of them since I was a fellow or unless I am consulted for vent management. I am in in hybrid units all the time… There speciality units are usually only in academic places where I work. Trauma patients still get managed by surgeons in academics. In the units I am in ( if I am not working in an academic center) the trauma guys consult ME for everything except OR related stuff. I see the… Read more »
Craig-I’m in Johns camp on this one. Can’t see any pt that phenyl brings anything to the table except where you don’t want to place a central line for prolonged infusions. John and I both believe in push-dose pressors (John correct me if I’m wrong on this one), but Push-Dose EPI rather than phenyl is where I have gone in pretty much everyone.
s
I understand the thought process and agree that levo is a better drug all around than phenyl. I was having some fun sparring with John a bit. I will use levo over phenyl when I can get it fast. I suspect that in the ED the drugs are on hand. In the ICU, i cant always get what I want …. which is painful since I am an only child so i dont deal well with not getting what I want. I can drop a line in a half an episode of sanford and son and still get a rush… Read more »
For what it’s worth, the more times I read you have big delays getting norepi in an ICU, the more insane it sounds. I think you may need to pick a fight with your pharmacy to routinely get the drugs you need on hand in your unit. If you’d prefer to give norepi but give phenyl instead, it’s a systems problem.
problem is many US hospitals don’t want non-sterile compounding going on anymore. So unless there is a premix, no unit stock. It is a problem.
Exactly, I am notice that some of our friends across the ponds are used to being able to have drugs on hand. I can get the drugs I need but due to the fact that I travel around, I sometimes am unaware of what each hospital pharmacy is able to do. I once had a patient in full status epileptics and had to call in the pharmacy to get more anti epileptics because only one dose was kept in the ED after seven pm. I had to give my first born to the ED doc to let me have it… Read more »
Craig, we wrote a protocol for peripheral norepi approved by pharm after the Ricard RCT. They really can’t argue when this is the only drug that has actually been studied. Just make sure there are arm checks going on.
Thanks
Scott Do you find epi has enough pressor effects (vs inotropy) when using it as a push-dose drug in sepsis / distributive shock? That’s the only reason I’ve tended to go with phenyl over epi while I’m waiting for the norepi to get down to that patient crashing on the floor at 3am. That and when we work ICU they seem to only have phenyl lying around for us to mix up and carry with us on ICU consults. Maybe a better solution would be to use push-dose norepi, but I’m assuming that isn’t done because of safety issues? Kevin… Read more »
Epi is a wonderfully potent alpha agent. There is always epi in every clinical venue, either in the nurse med station or if the pt is going downhill, ask for the crash cart. All you need is a 10ml syringe with 9ml of saline (also omnipresent) and you are good to go.
Have to believe norad unresponsiveness that is responsive to phenyl was simply a case of underdosed norad. Can’t see any pharmacologic reason why you would get a patient with better BP on matched vasopressor efficacy doses of both meds.
Scott, have thoughts on phenylephrine for vasospasm ppx in post SAH patients? Seems like an appropriate choice for the use (and classically used). Anyone using anything else?
Most of my neuroicu buds have switched to norepi. We are starting to believe the Triple-H should have a component of cardiac output rather than just pressure augmentation
Fantastic intro to pressors! Thanks for finally tackling this beast and making it palatable. Looking forward to the sequels.
Jessica Mason
Emergency medicine PGY2
thanks Jess!
Scott, I am curious as to where you begin to see diminishing returns with the use of Epi or other pressers. Based on some of the simple flow equations, as vessel lumen diameter decreases, resistance increases and reduces flow. Where then do you begin to work against yourself? If flow is the most important function (which is where I believe our focus should be) then why do we continually treat toward surrogates like coronary perfusion pressure? I have used the analogy lately in conversation that, I can close a door and create a tremendous pressure on one side, but if… Read more »
at least for what we have available in the lit mix right now; map of 65 seems to be the happy balance between pressure-dependent organs (heart) and flow dependent (distal tissues) assuming you have a relatively filled vasculature. Of course vasopressors in hemorrhagic shock are a beautiful example of a situation where a MAP of 65 achieved by vessel squeeze is a really nice way for the pt to die with the vitals looking good up until the code.
This was a great intro to an extreamly broad topic. During the talk you mentioned that you have all but stopped giving Phenylephrine as a push does pressor. Was there a specific reason for this? The program I work of gives us the option of both Phenylephrine and Epinephrine for push does pressor. I typically have opted to use Phenylephrine more often then Epinephrine due to tachycardia. It is also almost always either a bridge to a Norepinephrine infusion, or to correct hypotension s/p something we/they did ( RSI, analgesia, sedation, high PEEP/Pplat). Is Epinephrine the better option and should… Read more »
I like the fact that epi augments CO and therefore drug delivery in the peri-intubation. Phenyl prob slows the onset of intubation meds. And what I have found is that with phenyl the residents would mix up a big bag of the stuff and then it would sit around without monitoring or dates. Made me leery of multi-pt use, etc. Simplification to 1 drug is nice.
Scott, As usual nice podcast. Small thoughts that perhaps you’ll address on later podcasts: In general, the skill of the practitioner is more important than the pressor/inotrope used. One can use just about anything if the properties of the drug are well understood. A second issue is the presence of multiple receptor subtypes and patient SNPs that often complicate what should be classic receptor physiology. – Phenylephrine – we use this a lot in the OR as most hypotension here is simply afterload issues. For sick people I’ll usually put on something else. It has its place but wouldn’t be… Read more »
Erik, your comments are always fantastic.
We used much higher doses of Vaso (up to 0.08) in post-op cards pts, have not convinced myself in sepsis yet
Increases in lactate with epi can be seen clearly in the RCTs.
Much thanks for the terminology update on bact. translocation–what is the current, best descriptive way of discussing this entity?
thanks Erik
Thanks for the kind remarks. Not sure there is new terminology as of yet – some have called the ischemic process in the bowel “autodigestion”, although personally I dislike that word. I suppose one could continue to use “translocation”, except for the connotation with bacteria. Anyway, a fascinating and poorly understood subject that may turn out to be quite important. Cheers. Erik
Hi Scott/ EMCrit folks! Thanks for your casts, which are new to me. I am picking up at light speed, though. Excellent stuff! Have made my 2 hour daily drives to and from work so much more than just the hazzle of traffic. Any thoughts on Noradrenalin as pushdoses instead of phenylephrin/ ephedrin? I just spend some time in a cardiothoracic institution with this practice: Norepi/Noradrenalin is mixed to a concentration of 10 ug/ mL. Vasodilatatory hypotension in the periintubation setting is treated with pushdoses of 0,1 mL= 1ug peripherally until the patient is again normotensive and the central line… Read more »
other folks from your neck of the woods have mentioned the same. I’d love to see anything in print so that I could start doing this as well. Makes total sense
Thanks Scott. I appreciate these back to basics (but in depth) reviews a ton. I love learning about the cutting edge but this reflects what I’m dealing with (as a nurse working generally in medium-acuity settings) regularly and feel like I should know backwards and forwards.
Thanks!
Paul
(RN BSN CEN)
thanks Paul!
Hey Scott,
Re: phenyl, I generally feel the same as you & John- don’t like the drug and almost never use it. Have seen sick pts put on phenyl drips w/ great-looking BP’s & yet mottled skin. But one of your first descriptions of it’s use as a push-dose pressor was on an early Emcrit cast re: crashing A-Fib pt. As you move away from phenyl altogether, am I correct to assume you still use push-dose phenyl over Epi in these crashing A-Fib pts?
-Sam
What about the crashing a-fib patient? Any role for push does phenylephrine? Could I use push dose epi instead?
Larry DeWeil
I would be afraid to push epi in a crashing a fib patient….
think the style points still go to phenyl in this case, but Cliff Reid uses epi even in these patients and has not had a problem (Level 20 evidence)
Great talk- the bit about vasopressin not doing anything if the patient had endogenous stores…was that anecdotal or was there a paper you read on that topic? Hadn’t heard that before so would love to read that paper if it existed. ]
Thanks very much, Happy Holidays!
Adam
So how about putting norepi through an (US guided) proximal arm vein? I put in these lines all the time on the difficult to cannulate- as one of my registrars commented on a particularly proximal one ‘that’s almost central’….
any Evidence for central necessity? Certainly aware of two local cases where it’s gone arterial in a cvc mis-placement.
Reducing barriers to usage might mean people get this earlier not after 10litres of badness.
pressors through midlines is one of the things we are investigating now. as to regular IVs placed proximally, I would treat them just like peripheral.
By ‘Midline’, do you mean multi-lumen but in the arm?
I suppose the normal peripheral IVs have a frequent habit of tissuing………
Even the longer 48mm cannulas do this as they are often at an angle and go in deep.
yep, I actually feel safer with vasopressors through standard IV than the long ultrasound guided ones. On the other hand, a catheter that has its tip distant from puncture but still not central seems ideal. No evidence for this though.
Ok, up to speed with previous ‘cast. Midlines are potentially a massive game change esp in rural/ remote and retrieval. I couldn’t sleep last night thinking about this here in top end Australia. Sad I know…..
I’m not so concerned about the “falsely” elevated lactate with epi drips. It’s not like dopamine & urinary output — false reassurance is bad because it (falsely) gives us permission to stop aggressively resuscitating the patient. Falsely elevated lactates, however, are a different boat: of course I’m concerned about the patient — they’re sick enough to need an epi drip!
good point so long as the response to elevated lactate is not to keep giving extra fluid
Scott great talk as always-at LIJ, in Dr. Paul Mayo’s ICU- we almost never see central lines being used anymore. I have a question for you or anyone willing to comment- in those really bad CHF patients who come in with septic shock, and are tachy, I prefer phenylephrine to keep their MAP above 65 and this also helps with coronary perfusion, though some say that this increases afterload and is therefore not good in CHF and that coronary perfusion is not the main issue. I really can’t find a lot of good literature on these patients with perhaps a… Read more »
Mohammed, Very good question! I also don’t have the answer. Lots of those folks are pretty tachy either on sinus or a-fib, and over 120 the CO must be going down. In paroxistic a-fib you can shock it away but it will likely return. In chronic, you may try digoxin (not very effective or safe) or amiodarone (it will not convert them but it will slow them down). In sinus it would be great to have IV ivabradine, but maybe it would increase the number of a-fibs. I’m not using phenyl but it has some rational, especially if you monitor… Read more »
All the above is valid in the context of norepi/dobu requiring patients, of course, not an otherwise healthy a-fib patient!!!
Yep, I have NEVER seen levo or epi causing bradycardia.
Scott, great podcast as usual.
Where does the 20 mcg threshold comes from? Any lit ou personal experience?
Best,
Miguel
Scott,
I am working in a remote practice (north slope of Alaska) and will be soon affected by the Vasopressin shortage. We are discussing taking it off our formulary. The feeling is that Epi and Norepi are the primary treatments, so why bother having Vasopressin in our armamentarium? Is it used as a primary treatment in any situation? Will it work when the others don’t?
Jose Diaz PA-C
Thanks Dr. Weingart- one of my favorite episodes ever. You mention a recent discover that low-dose vasopressin does nothing unless the patient is ADH-deficient. Basically, low dose vasopressin infusions are for ADH-repletion. I’ve heard this from our intensivists as well: can you help point me toward the evidence for this? I’ve found one paper but have struggled to find much more. Thanks so much- strong work!
the only stuff I’ve seen is pre-clinical research out of Vanderbilt for trauma patients. If you find anything, send it my way.
Hi Scott. Love the show! My favorite podcast by far. My comment is a little off topic, but worth discussing nonetheless. You made a comment about the importance of avoiding/preventing gut ischemia due to the potential for it to lead to increased morbidity & mortality. I am not disputing this. However, it sounds like the mechanism for this is not due to bacterial translocation as we were all classically taught. I recently listened to a podcast from SCCM – iCriticalCare episode 381 with Dr. Craig Coopersmith from April 2 of this year discussing the role the gut plays in MODS.… Read more »
Links seem to be broken now? 🙁
not sure what you are referring to