# Levophed/Norepinephrine?



## lightsandsirens5 (Jun 4, 2013)

Do you use it? I am kind of curious to see who does? I used it for the first time last night and the nurse could not believe I brought someone in from the field on a Levo drip.

I was truly impressed by it and am very grateful that I had it at my disposal. I no like BP of plus or minus 50/20, especially in a pt completely refractory to 1000 ccs of NS who's MAP continued to decrease.


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## chaz90 (Jun 4, 2013)

I haven't been anywhere that had Levo in the field. I know of some places that used to use it, but they've gone to Dopamine as the only EMS pressor now. Do you have a choice of Levophed vs. others?

Was your patient septic by the way? That's the time I'd most like to have a more alpha specific agonist.


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## MagicTyler (Jun 4, 2013)

I've heard a rumor that Levo is being added to Arizona drug list, and is preferred over dopamine for hypotention not related to hypovalemia


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## lightsandsirens5 (Jun 4, 2013)

For pressor drips I can hang Levo, Dopamine and Epi. 

I'm thinking he was septic. That is the only thing that makes sense.

What really sucked, and the reason I had to hang Levo, was we had to RSI him cause I was loosing the airway. And the only way to keep him down was with Versed. And the only way to keep his sats out of the toilet was with 10 of peep. So it KILLED his pressures. And a liter of saline did squat, so I went with the Levo. It worked like a charm though.


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## chaz90 (Jun 4, 2013)

Yeah, I can see Versed plus 10 of PEEP being bad news in an already septic patient. Sounds like good work and a cool call though!


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## mrg86 (Jun 4, 2013)

We just started using it in my county, it is first line for septic/neurogenic shock that is refractory to fluids. 8-12 mcg/min titrated to effect and then backed down if BP allows.


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## STXmedic (Jun 4, 2013)

We've got it as a pressor option, along with dopa (no epi). Our doc also wants it initiated on all ROSC patients. I've given it once with seemingly good success at a previous employer (septic patient after a liter and a half).


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## Ecgg (Jun 4, 2013)

Well is certainly works, it's why they called it Levophed or leave 'em dead. Although "raising the bp" is not a measure of success, without knowing end organ perfusion status and urine output.

You guys use IV pumps, or gravity drips?


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## Dwindlin (Jun 4, 2013)

Not sure I get get the warm and fuzzies from pre-hospital use of levo.  There are concerns of putting through a peripheral line, dopa is much safer in this aspect.  Not to mention if you really think the patient was septic then I wouldn't expect much from one liter.  These patients tend to get massive amounts of fluid resuscitation before we admit defeat and start pressors.  

Personally I feel about pressors the way I feel about vents.  Use as infrequently as humanly possible, in as small amount as absolutely necessary, for as short amount of time as humanly possible.


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## Summit (Jun 4, 2013)

Peripheral levo is a bit scary. Central levo can have some nasty side effects too, but it is great in the septic pt among others.

The reason that 1L NS did nothing in a septic patient is because they probably needed 6L or 12L or more. Med control ought to approve more fluid.


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## Ecgg (Jun 4, 2013)

Summit said:


> Peripheral levo is a bit scary. Central levo can have some nasty side effects too, but it is great in the septic pt among others.
> 
> The reason that 1L NS did nothing in a septic patient is because they probably needed 6L or 12L or more. Med control ought to approve more fluid.



12L more? Probably after 2nd bolus of 20ml/kg with that BP would be good idea to think about a pressor, unless the patient is 600lbs.


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## WTEngel (Jun 4, 2013)

We would use norepinephrine for our sepsis protocol back when I was doing CC transport.

I am reaching back to biochem class here...I seem to remember that norepinephrine has the lowest pKa of the four pressors we commonly use (epi, norepi, dopamine, dobutamine.) this in and of itself doesn't mean anything spectacular, other than the fact that the higher the pKa of the drug, the less effective it will be in an acidic environment. Most septic patients we are dealing with are acidic.

Also, dopamine is a precursor of epi and norepi. In acidic conditions, the pathway it takes to convert to norepi and epi will not proceed as effectively as it would when conditions are a homeostatic 7.4. Remember, pH is logarithmic, so even a slight move has magnitudes of effect on h+ concentration.

All this is to say, in my experience, norepi was a better drug in profound sepsis, and I believe it has to do with the acidosis we find many septic patients in. This is why in many protocols, norepi is first line for SERIOUS sepsis, but can be preceded by dopamine in early stage or even moderate sepsis.

The last thing ill add (in this post anyway) is that septic patients are a balancing act, and I rarely managed them with only a single pressor. Generally it was a combination of pressors, while keeping an eye on end organ perfusion, pH, lactate, pyruvate, etc.


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## Ecgg (Jun 4, 2013)

WTEngel said:


> We would use norepinephrine for our sepsis protocol back when I was doing CC transport.
> 
> I am reaching back to biochem class here...I seem to remember that norepinephrine has the lowest pKa of the four pressors we commonly use (epi, norepi, dopamine, dobutamine.) this in and of itself doesn't mean anything spectacular, other than the fact that the higher the pKa of the drug, the less effective it will be in an acidic environment. Most septic patients we are dealing with are acidic.
> 
> ...



I think it's much more simpler. Septic shock is a distributive shock (AKA warm shock in adults mostly ~70% gram negative LPS) due to massive release of nitric oxide severe dasodialtion occurs through the body, I would imagine alpha drug would be a better choice at the stage OP patient was.


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## WTEngel (Jun 5, 2013)

I understand that sepsis is a distributive form of shock and I realize the patho behind its onset. 

I think you're missing my point... Norepinephrine is synthesized from dopamine anyway...so one would reasonably believe that dopamine should be just as good in sepsis, because it will ultimately increase endogenous norepinephrine, right?

This is not the case however, as that pathway will not proceed reliably in acidic conditions. So we give norepinephrine straight away, because endogenous norepinephrine biosynthesis has been largely stalled.

We both agree that norepi is a good drug of first choice for sepsis.


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## Arovetli (Jun 5, 2013)

Ecgg said:


> 12L more? Probably after 2nd bolus of 20ml/kg with that BP would be good idea to think about a pressor, unless the patient is 600lbs.



Pressors are typically 2nd line behind fluid resuscitation...perhaps only to be used after adequate resuscitation attempts, often of multiple liters of fluid, have failed or pulmonary edema develops. EGDT suggests about 5 liters, and early abx/fluids over pressors if possible.


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## Handsome Robb (Jun 5, 2013)

No levo here, only dope (standing) and Epi (for bradycardia and hypoTN refractory to TCP and dope after MD contact...never ever heard of someone hanging one).

As far as fluids go, 1L isn't a lot, we have to give 2L before we can go to a pressor unless we really have a good reason. 

Dope isn't a great choice for most of the patients that I see that need a pressor, it'd be awesome to have levophed but I don't see it happening anytime soon.


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## STXmedic (Jun 5, 2013)

I've heard of the poor effects of levo through a peripheral line. However, I've asked many EM docs and a couple intensivists, and all have given me the same answer: in the short term, it is not a concern.


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## lightsandsirens5 (Jun 5, 2013)

Man, I am still baffled, because the pre RSI pressure was 13x/8x. So it wasn't like I was thinking Sepsis at that point. 

The other issue was he had a Hx of CHF, and his breath sounds were already horrible. So I really didn't feel like dumping 6000 CCs into him. 

What kind of complications are we talking with peripheral Levo? Severe vasoconstriction? We start it at 2 mikes/min, which I am assuming isn't too bad?

Ecgg: I wasn't too concerned with urine output in the field, but MAP/BP is all we have to really look at to make an educated guess as to if end organ perfusion is actually occurring? Or am I missing something?


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## Ecgg (Jun 5, 2013)

WTEngel said:


> I understand that sepsis is a distributive form of shock and I realize the patho behind its onset.
> 
> I think you're missing my point... Norepinephrine is synthesized from dopamine anyway...so one would reasonably believe that dopamine should be just as good in sepsis, because it will ultimately increase endogenous norepinephrine, right?
> 
> ...





Arovetli said:


> Pressors are typically 2nd line behind fluid resuscitation...perhaps only to be used after adequate resuscitation attempts, often of multiple liters of fluid, have failed or pulmonary edema develops. EGDT suggests about 5 liters, and early abx/fluids over pressors if possible.





http://www.sccm.org/Documents/SSC-Guidelines.pdf

(1C); initial fluid challenge in patients with sepsis-induced
tissue hypoperfusion and suspicion of hypovolemia to achieve a
minimum of 30 mL/kg of crystalloids (more rapid administration
and greater amounts of fluid may be needed in some patients)
(1C); fluid challenge technique continued as long as hemodynamic
improvement, as based on either dynamic or static variables
(UG); norepinephrine as the first-choice vasopressor to
maintain mean arterial pressure ≥ 65 mm Hg (1B); epinephrine
when an additional agent is needed to maintain adequate blood
pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine
to either raise mean arterial pressure to target or
to decrease norepinephrine dose but should not be used as
the initial vasopressor (UG); *dopamine is not recommended
except in highly selected circumstances*


So OP patient is refractory to fluid bolus, granted 1L is low, but it should not be 12L by any means.

say 90kg patient i'd give 2 (20ml/kg that is 3.6L total) bolus if refractory still, I may do 1 more if no pul edema and then go for the presssor.


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## WTEngel (Jun 5, 2013)

MAP is a decent indicator of perfusion (better than straight BP) but the primary concern in patients we start pressors on is renal perfusion. In some cases we end up in a "rob Peter to pay Paul" situation, stealing perfusion from the kidneys by way of vasoconstriction, in order to maintain cerebral and cardiac perfusion.

In the short term, you have to do what you have to do, in the long term, you'll end up chasing renal function and metabolic derangements for days if not weeks.


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## WTEngel (Jun 5, 2013)

Ecgg, then we agree on the treatment (or should I say the link you posted agreed) just not the rationale. At this point I guess it really doesn't make too much of a difference.


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## Ecgg (Jun 5, 2013)

lightsandsirens5 said:


> Ecgg: I wasn't too concerned with urine output in the field, but MAP/BP is all we have to really look at to make an educated guess as to if end organ perfusion is actually occurring? Or am I missing something?



In the field is hard to assess. Hence why I asked if you running a pump and titrating it to MAP? 

Usually if it's gravity drip in the hands of medics and nice bumps in transport, I am certain the pressure would be amazing upon arrival, but there would be profound vassoconstriction.


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## Ecgg (Jun 5, 2013)

WTEngel said:


> Ecgg, then we agree on the treatment (or should I say the link you posted agreed) just not the rationale. At this point I guess it really doesn't make too much of a difference.



You may be correct about the pathway, I need to review some of my lectures.


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## Carlos Danger (Jun 5, 2013)

WTEngel said:


> I think you're missing my point... Norepinephrine is synthesized from dopamine anyway...so one would reasonably believe that dopamine should be just as good in sepsis, because it will ultimately increase endogenous norepinephrine, right?



The beta effects of dopamine are undesirable in most patients, though. The tachycardia associated with dopamine can increase Mv02 dramatically.

The easiest to use / safest pressor IMO is phenylephrine. Vasopressin works well in many patients, also.


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## Summit (Jun 5, 2013)

Surviving Sepsis 2012 Update information here: http://www.survivingsepsis.org/Guidelines/Pages/default.aspx

Ecgg: I referred to what the patient might need thus the lack of response to a 1L bolus, not what they should definitely receive on the ambulance. It is unlikely such a large amount would be ordered on an ambulance without serial lactates and a metric to measure volume/preload status (CVP is usually used in sepsis although some question its reliability) particularly with a CHF history. I’ve certainly seen bigger patients in severe septic shock get 12L+ over the course of <2hrs and be on levophed and vaso.

LS5: CHF hx is not a contraindication to fluid resuscitation in the septic patient, but it is a good indicator for close attention.


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## Dwindlin (Jun 5, 2013)

Ecgg said:


> http://www.sccm.org/Documents/SSC-Guidelines.pdf
> 
> (1C); initial fluid challenge in patients with sepsis-induced
> tissue hypoperfusion and suspicion of hypovolemia to achieve a
> ...



Principle is sound, but in life most intensivists aren't going to consider pressors in sepsis after only 3 - 4 liters.  The way I have been taught is actually fairly similar to Dr. Weingart's (from emcrit) preferred method.  We don't like CVP, we use ultrasound.  We give continuous fluids (large bore and with a pressure bag for the first several liters, but never on a pump) until BP improves or until there NO IVC COLLAPSE (notice we don't use that 13% collapse or what ever it is).  Rarely will the patients end up with less than 8 - 10 liters before we start the pressor talk with patient/family.  

As far as pressors go.  We do some form of sympathomimetic (whether that is levo, epi, or dopa) and if we need a second we do a non-adrenergic (vaso generally).  We don't stack adrenergic pressors here (thank god).


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## Carlos Danger (Jun 5, 2013)

lightsandsirens5 said:


> For pressor drips I can hang Levo, Dopamine and Epi.
> 
> I'm thinking he was septic. That is the only thing that makes sense.
> 
> What really sucked, and the reason I had to hang Levo, was we had to RSI him cause I was loosing the airway. And the only way to keep him down was with Versed. And the only way to keep his sats out of the toilet was with 10 of peep. So it KILLED his pressures. And a liter of saline did squat, so I went with the Levo. It worked like a charm though.



Could have been sepsis, or possibly something else. There are a lot of conditions that will cause a transient (or not so transient, if not treated) hypotension on induction. Sepsis is certainly one of them. 

What was the rest of the clinical picture? How much midazolam did you give? What drugs did you use to RSI?


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## lightsandsirens5 (Jun 6, 2013)

So just did follow up and found out he had a large hemorrhagic CVA. Go figure.

Now, as to me only using 1L of fluids, the main reason was not just the Hx of CHF, but the fact that he was already nearly drowning with Pulm. Edema.

Halo: 74 yom found unconscious by spouse at 0230 hours. Upon arrival GBG of 42. 25g of D50%W to no effect. Move to MICU, beginning of decline in resp. status. Corresponding decrease in saturation and increase in end tidal. Decide to RSI. Pre-induction vitals of: P:70. R: 8. BP: 130/80 (approx). SPO2: 88 (bagged up to 99 pre-induction). ETCO2: 50. GCS: 6 (1,1,4) Temp: 98.3F. Approx 75kg Male. For RSI, Drugs: Fent. 100mcg. Ketamine 125mg. Roc 75mg. Pass tube and confirm. Rapidly desaturated without PEEP. Needed 10 cmH2O to keep sat in mid 90s. Vitals of: P: 60. R. 14 (to keep end tidal at acceptable levels) BP: 100/70. SPO2: 96% (Without PEEP was 88%). ETCO2: 42. 15 minutes later begins to buck tube. 5 mg of midaz. That is when the floor fell out of his pressure. 50/20. 1L of fluid with zero effect. Horrible sounding edema. Turning PEEP up only dropped his MAP further. So I started Levo @ 4mcg/min. Brought his pressure to about 100/50. So I know I got CP with that. I hope I didn't vasoconstrict him so much I killed renal perfusion. Though with the size stroke he had, I doubt he will need it for long.

And yes the Levo was on a pump. I have to use the pump for all med drips. Which I would do anyhow.


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## VFlutter (Jun 6, 2013)

lightsandsirens5 said:


> Brought his pressure to about 100/50. So I know I got CP with that. I hope I didn't vasoconstrict him so much I killed renal perfusion. Though with the size stroke he had, I doubt he will need it for long.



Eh, I highly doubt you were actually getting cerebral perfusion. Even in the presence of normal ICP you are barley getting adequate CPP with that MAP. And most likely this guy's ICP was markedly elevated. 

In the NICU it was not uncommon to max out multiple pressors to maintain crazy high MAPs in TBI/CVA patients. 

If the patients ICP was 40 (Unconsciousness) then you would need a MAP of 110 just to maintain a minimum CPP of 70. Which is roughly 160/100....

But as Vene would say you can't just chase numbers.


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## Carlos Danger (Jun 6, 2013)

Doesn't really sound like sepsis. Maybe the PEEP + fentanyl + midazolam caused the hypotension, especially if his EF was already low. Good job with the patient management.

I thought this was interesting: Medscape

Importantly, recognize that neurogenic pulmonary edema is an underdiagnosed condition. Patients with neurologic events often have multiple other comorbidities, which may obscure or mimic the diagnosis of neurogenic pulmonary edema. The lack of a standardized definition for neurogenic pulmonary edema also makes defining its epidemiology difficult.

As many as one third of patients with status epilepticus may have evidence of neurogenic pulmonary edema.[5] More than half the patients with severe, blunt, or penetrating head injury have associated neurogenic pulmonary edema. Approximately 71% of fatal cases of subarachnoid hemorrhage are complicated by neurogenic pulmonary edema. Neurogenic pulmonary edema may complicate subarachnoid and intercerebral hemorrhage in 30-70% of patients and may recur after initial resolution.[6, 7]

A series of 457 patients with subarachnoid hemorrhage reported a 6% prevalence of severe neurogenic pulmonary edema.[8] Solenski et al reported in 1995 that increased age and a worse clinical grade of subarachnoid hemorrhage were associated with neurogenic pulmonary edema.


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## FLdoc2011 (Jun 7, 2013)

You can also get direct cardiac dysfunction from severe neurological insults such as neurogenic stunned myocardium.     

Have seen in quite a bit in severe strokes or intracranial hemorrhages where they have relapse of troponin and/or evidence of heart failure.


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## Flight-LP (Jun 7, 2013)

Halothane said:


> The beta effects of dopamine are undesirable in most patients, though. The tachycardia associated with dopamine can increase Mv02 dramatically.
> 
> The easiest to use / safest pressor IMO is phenylephrine. Vasopressin works well in many patients, also.



I was reading thought the thread and wondering when someone was going to bring up this truth!

Neosynephrine is the way to go. It's safer, more effective on those acidic septic patients, and easier to administer than the typical multitude of pressor drips we commonly see. Plus I've rarely seen the need to add more pressors in comparison to hanging levophed. Just my personal experience though, individual results will vary. 

I had the perfect example earlier this week. Septic patient, intubated, on Vanc and Cipro for Imperical coverage, on a bit of Cardizem, a little Insulin, Diprivan (?!?WTF over?!?), and THREE freaking pressors (Levo, Vaso, and Dopamine). Pressures were running in the 70's. 

Yes this was what we term an inter facility rescue, although they did at least attempt to treat, lol. 

After stopping the Diprivan (***cough***blood pressure***cough), killing all the pressors and starting neo, and then getting some fluid going, the pressure stabilized. Once at a decent perfusing level, we were able to reintroduce sedation and keep his pressure stabilized with only the neo. 

I think the take home message is and should be that more is not always better. Over complicating the septic patient can be fatal or at least catastrophic. Of course so can under complicating, but I digress................


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## Carlos Danger (Jun 7, 2013)

Flight-LP said:


> I was reading thought the thread and wondering when someone was going to bring up this truth!
> 
> Neosynephrine is the way to go. It's safer, more effective on those acidic septic patients, and easier to administer than the typical multitude of pressor drips we commonly see. Plus I've rarely seen the need to add more pressors in comparison to hanging levophed. Just my personal experience though, individual results will vary.
> 
> ...



Sounds like fun. I've been on more of those interfacility rescues than I could even begin to recall.

Let me guess.....they had dopamine on to counteract the myocardial depression of the propofol, and cardizem running to counteract the tachycardia and ectopy from the maxed out dopamine? 

A practice that I developed for these situations was to significantly reduce or even DC everything that wasn't obviously necessary (i.e. here I probably would have left on the levo and vaso, as well as the ABX, and turned the rest off), re-evaluate the patient, and then systematically add things back in or turn more things (vaso) off as indicated. And of course these patients are almost always under-resuscitated with IVF.

A lot of times the bedside nurses or referring docs weren't happy about it, but much more often than not, I was able to safely transport the patient with a lot fewer infusions to worry about and a lot less polypharmacy to cloud things.

In my experience, propofol is not a good sedative by itself for transport anyway, and I have often replaced a propofol infusion with boluses of midazolam and fentanyl, even in patients who aren't hypotensive.


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