#6 Vasopressors Part 1: Pressor Basics

Hemodynamics
Written By Nick Mark

On this episode of Critical Care Time, Cyrus and Nick explore the basics of vasopressors, providing a framework for understanding them. When to start them, how to titrate them, when to use push dose vasopressors, and when a central line is needed. If you use vasopressors to treat your patients, this is the episode for you! Whether you are ordering them, titrating them or looking out for complications associated with their use, Nick & Cyrus have got your back!


Quick Take Home Points

  1. Be comfortable with the different classes of vasopressors (catecholamine vs non-catecholamine) and how they work / when to use which ones!

  2. Remember: The goal of vasopressors is to enhance oxygen delivery. 

  3. In undifferentiated shock, consider norepinephrine to be the vasopressors of choice.

  4. Vasopressors may be the answer in a patient in shock… or they could be harmful! Don’t hesitate to start vasopressors while working up your patient’s shock state, but remember that they don’t fix everything (e.g. tension pneumothorax or frank hemorrhagic shock).

  5. Be on the lookout for cryptic shock - a shock state that isn’t overt on initial evaluation. For example, a patient that “looks'' okay with a “normal'' blood pressure… who at baseline is on multiple anti-hypertensive agents!

  6. An ounce of prevention is worth a pound of cure: Remember to have vasopressor infusions running and push-dose vasopressors ready during high risk interventions such as RSI

  7. Vasopressors can be given through a good peripheral IV, but make sure you have a plan to manage extravasation if it occurs.

  8. Central venous catheters have uses beyond vasopressor administration and can definitely be helpful, in addition to mitigating extravasation risk - but the absence of a central line should not delay vasopressor administration

Show Notes:

  1. What are vasopressors?

    • Vasopressors are medications that increase systemic vascular resistance (SVR) and consequently blood pressure.

      1. Usually we focus on the Mean Arterial Pressure (MAP) because this is (usually) the best predictor of organ perfusion.

      2. Diastolic BP if often low in septic shock (low SVR)

      3. Pulse Pressure (SBP - DBP) correlates with stroke volume (SV); suspect low SV if you see a low PP.

    • Two-main buckets

      1. Catecholamine vasopressors (adrenergic receptor agonists)

        1. Alpha Adrenergic Receptors:

          1. α1: vascular smooth muscle

        2. Beta Adrenergic Receptors:

          1. β1: contractility/heart rate

          2. β2: bronchodilation

        3. Phenylephrine: Pure, unopposed alpha activity - raises SVR. Does not increase CO. (Often CO falls due to higher after load)

        4. Norepinephrine: Significant alpha activity, with some beta 1 activity - raises SVR along with mild-to-moderate increase in cardiac output (CO). Less arrhythmogenic than vasopressors with more “beta” activity (dopamine, epinephrine)

        5. Epinephrine & Dopamine: alpha & beta activity, provides more balanced increase to SVR and CO at the “expense” of promoting tachycardia and/or being arrhythmogenic

        6. Isoproterenol & Dobutamine: NOT vasopressors, but are catecholamine beta agonists that are instead inodilators (i.e. inotropes that also cause vasodilation)

      2. Non-catecholamine vasopressors (do NOT work on adrenergic receptors)

        1. Vasopressin

          1. Works primarily on V1a receptor

        2. Angiotensin II

          1. Works primarily on AT₁ Receptor

    • How do vasopressors work?

      1. First and foremost: vasopressors are arterial vasoconstrictors, increasing perfusion - particularly helpful by increasing SVR and tissue perfusion

      2. Also can increase pre-load via venoconstriction, providing some (generally temporary) support during non-distributive shock states via augmenting RV filling volume/pressure

      3. Certain vasopressors (see above) not only support the SVR but also improve cardiac output via increases to inotropy & chronotropy - helpful in the setting of depressed cardiac output

    • Caveats and considerations

      1. Use vasopressors while evaluating the patient to temporize their shock state - it’s important to diagnose the patient, however, remember that in critical care diagnosis often comes after stabilization

      2. Norepinephrine is usually a fine first choice when managing shock, with some exceptions:

        1. Cardiogenic shock: epinephrine may be a good choice to increase inotropy

        2. Anaphylactic shock: epinephrine is a great choice given beta-2 effects and consequent bronchodilation

        3. Correcting a “pure” drop in SVR: (e.g. an epidural causing systemic vasodilation from an iatrogenic cause) … phenylephrine might be a good first-line option

        4. Dynamic LV Outflow Tract Obstruction: increases in inotropy increase the gradient across the outflow tracts and can make things worse… so phenylephrine may be a good option here too. See part 2 for more on Dynamic LVOT obstruction and choice of vasopressos.

  2. Indicators that a vasopressor may be indicated (in the right content, e.g. a patient in shock)!

    • Altered mental status

    • Delayed capillary refill (> 2 sec)

    • Drop in mean arterial pressure (or increased pulse-pressure)

      • NOTE:You don’t have to be frankly hypotensive to be in shock and to need vasopressor support

      • We also know there are plenty of folks who are hypotensive at baseline who are not in shock: patients with certain neurologic diseases, single ventricle physiology or those with chronic liver disease for example

    • Increasing heart rate

    • Increasing serum creatinine / AKI and/or decreasing UOP

      • NOTE: Don’t chase UOP as the sole indicator that shock is improving, it takes a while for UOP to rebound after the shock state has been improved… especially if the patient has an increased CVP thereby reducing their renal perfusion pressure (RPP=MAP-CVP)

      • It’s also not that helpful in anuric renal failure unless you are expecting a miracle!

    • Worsening liver function tests

    • Worsening lactate trend

      • A “normal” lactate is less than 2, but the trend is what matters! 

      • Lactate is not harmful - remember that elite athletes can generate massive amounts of lactate

        • Myocardial energy during times of stress is derived in large part from lactate - this is adaptive!

      • The rub is what is causing the elevated lactate?

        • Production vs clearance 

      • Beta-agonists (epinephrine, albuterol) increase lactate production

      • Lactated Ringer’s (LR) does not increase serum lactate, however, drawing from a vein recently exposed to LR will result in a spuriously high lactate

    • An increase in the “delta-CO2” or the “pCO2 gap”

      • CO2 Gap = venous pCO2 - arterial pCO2  

        • Normally the CO2 gap should be ≤ 6

      • pCO2  - the partial pressure of carbon dioxide in the blood - is the principle byproduct of aerobic cellular respiration, thus it varies with cardiac output

      • Venous pCO2 is representative of the amount of metabolism occurring at the tissue level, relative to blood flow - the better the blood flow, the lower the venous pCO2 will be because those capillary beds are constantly being supplied with fresh blood that is relatively high in oxygen and low in carbon dioxide

      • When perfusion is limited (such as in shock), there is an increase in the ratio of cellular respiration performed per unit time relative to blood flow through the tissue bed, resulting in increased carbon dioxide production

      • CO2 - being highly soluble - readily diffuses from the relatively ischemic tissues into the venous circulation, resulting in an increase in the venous pCO2  which based on the equation, necessarily results in an increase in the pCO2 gap assuming arterial pCO2 remains the same

      • In practice, we don’t have this value often because it is rare that an ABG and VBG will be drawn at the same time, however, when this does happen - often by accident - it can provide useful data if recognized!

  3. Titrating vasopressors

    • We usually use a MAP of 65 because we know that should be enough to ensure adequate tissue perfusion (brain, kidney, gut)

      • Heart is perfused during diastole so targeting a higher diastolic (such as > 40 mmHg) may be reasonable in certain populations 

      • Also consider perfusion: renal perfusion (MAP - CVP), cerebral perfusion pressure (MAP - ICP)

    • The 2020 65 Trial suggests that targeting a MAP goal of 60-65 mmHg did not negatively impact mortality versus traditionally higher MAP goals in the ICU; it also shortened duration of vasopressor dependence.

      • Multi-center, RCT, n=2463 patients in 65 UK ICUs where the intervention group was treated to a MAP goal of 60-65 mmHg versus “usual care,” which resulted in a peak-MAP difference of approximate 10 mmHg between groups

      • Patients: >65 y/o in early vasodilatory shock

      • Exclusions: included patients being treated for brain injury, those on vasopressors for acute ventricular failure, among others

      • Subgroup of patients with chronic hypertension did better with a lower MAP goal (60-65 mmHg)

      • Weaknesses: open-label, unusually high mortality in usual care group, population limited to >65 yo, and significant use of “metaraminol” make generalizability somewhat questionable

  4. To push or not push - Push-dose Pressors

    • When?

      • When someone is in extremis (a BP of 45/25 does not need to start a norepinephrine drip, they need a bolus dose FAST)

      • When the change in BP is transient - for example induction medications with to intubation

    • Let’s talk RSI (Rapid Sequence Intubation)

      • RSI drugs often strip someone of their high sympathetic tone immediately prior to intubation, resulting in significant swings in blood pressure

      • Hypoxemia/hypercapnia - often present prior to intubation - can reduce SVR & CO

      • Positive pressure ventilation initiated immediately after intubation can reduce preload (especially in under-volume resuscitated patients) which can reduce cardiac output and BP

    • So what can we do?

      • Consider starting a low-dose vasopressor infusion (such as norepinephrine) prior to intubation so that it can easily be uptitrated if needed, rather than started from scratch

      • Have a bolus of IVFs ready to go

      • Have push-dose pressors in hand

    • Push-dose pressor overview

      • Have your push-doses ready and waiting before RSI or other procedures that are likely to cause hypotension

      • Consider given several small doses rather than overshooting

      • If you have in-line pressors going, increase that dose while you are giving the push-dose pressors

      • Nick: If you are doing things acutely, monitor acutely. Consider placing an arterial line before a high risk procedure (such as RSI, assuming there is time) so you can have high-fidelity, real-time numbers to base decisions off of

      • Usual Options

        • Pre-filled syringes are superior to mixing meds on the fly!

        • Epinephrine

          • 20-50 mcg push & flush

          • Can be made from “code-dose” epinephrine by replacing 1mL of sterile saline in a saline flush with 1mL of “code-dose” epinephrine (1mg/10mL), resulting in a syringe with 100 mcg of epinephrine, or 10 mcg/mL

          • Good choice in those with bradycardia and hypotension

          • Good choice when uncertain as to patient’s cardiac history, although it can trigger transient tachycardia & tachyarrhythmias  

        • Phenylephrine

          • 100-200 mcg push & flush

          • Often available in 10mL syringes at concentrations of 40 mcg/mL or 100 mcg/mL

          • Not recommended in those with known left-ventricular failure

          • Not recommended in bradycardia as this can cause worsening bradycardia

        • Vasopressin

          • 1-2u push & flush

          • Warning: No antidote if extravasation occurs - strongly recommend use with central venous lines only!

Peripheral Vasopressors - specifically the catecholamine vasopressors - can be pushed and infusion via peripheral IV - a central line is not necessary

  • The IV should be a “good” IV which we loosely define as one that is not in a small vessel

  • Via U/S the vessel should be >4mm in size

  • The catheter should take up 50% or less than the size of the vessel 

  • The IV should be a 20g or larger, which allows you to draw and flush

  • Avoid high risk areas - places where the IV can easily dislodge or extravasation can be missed - not the feet or hands, not the AC, ideally in a forearm

  • Know what to do if extravasation occurs (see below) 

Extravasation - the “Mark Protocol”: 

    1. Can be seen with push-doses of vasopressors or infusions given via peripheral IV

    2. What do you do if extravasation is suspected: 

      1. Antidote is phentolamine (5 mg in 10mL of saline)

      2. Stop the vasopressor infusion but leave the catheter in place

      3. Take a syringe and try to aspirate any medication/ from the area

      4. With the catheter still in place, inject IV phentolamine directly into the site, and slowly draw back the catheter - treating the whole “tract” with phentolamine

      5. Inject the remaining phentolamine around the site via  23g syringe

        1. Be mindful of where the tip of the catheter was (not the puncture site) and use that as the frame of reference when injecting subcutaneous phentolamine

      6. Mark off the area and monitor it closely, repeatedly 

      7. If you need to keep them on their pressor, switch the line to another peripheral IV… but make definitive access (i.e. a central line) a high priority

Audio

Video

Nick Mark
Previous

#7 Vasopressors Part 2: Beyond the Basics
Next

#5 Zorses & Hebras: A New Take on an Old Adage