Vasopressors

Background

  • Goal is to reach critical organ perfusion pressure
    • Brain: MAP of 50 mmHg [1]
    • Heart: MAP of 65 mmHg
    • Kidneys: MAP 65-75 mmHg[2]
  • IV Vasopressor have not been shown to be unsafe when used peripherally[3] If running peripherally perform frequent site check via institutional protocol. [4]
    • Ideally use proximal (antecubital fossa) large-bore IV (at least 18-gauge)

Types

Vasopressors

Pressor Initial Dose Max Dose Cardiac Effect BP Effect Arrhythmias Special Notes
Dobutamine 3-5 mcg/kg/min 5-15 mcg/kg/min (as high as 200) [5] Strong ß1 agonist +inotrope +chronotrope, Weak ß2 agonist +weak vasodilatation ) alpha effect minimal HR variable effects. indicated in decompensated systolic HF, Debut Research 1979[6] Isoproterenol has most Β2 vasodilatory and Β1 HR effects
Dopamine 2 mcg/kg/min 20-50 mcg/kg/min β1 and NorEpi release α effects if > 20mcg/kg/min Arrhythmogenic from β1 effects More adverse events when used in shock compared to Norepi[7]
Epinepherine 0.1-1 mcg/kg/min + inotropy, + chronotropy
Norepinephrine 0.2 mcg/kg/min 0.2-1.3 mcg/kg/min (5mcg/kg/min) [8] mild β1 direct effect β1 and strong α1,2 effects Less arrhythmias than Dopamine[7] First line for sepsis. Increases MAP with vasoconstriction, increases coronary perfusion pressure, little β2 effects.
Milrinone 50 mcg/kg x 10 min 0.375-75 mcg/kg/min Direct influx of Ca2+ channels Smooth muscle vasodilator PDE Inhibitor which increases Ca2+ uptake by sarcolemma. No venodilatory activity
Phenylephrine 100-180 mcg/min then 40-60 mcg/min 0.4-9 mcg/kg/min Alpha agonist Long half life
Vasopressin Fixed Dose 0.01 to 0.04 U/min unknown increases via ADH peptide should not be titrated due to ischemic effects
Methylene blue[9] IV bolus 2 mg/kg over 15 min 1-2 mg/kg/hour Possible increased inotropy, cardiac use of ATP Inhibits NO mediated peripheral vasodilation Don't use in G6PD deficiency, ARDS, pulmonary hypertension
Medication IV Dose (mcg/kg/min) Concentration
Norepinephrine (Levophed) 0.1-2 mcg/kg/min 8mg in 500mL D5W
Dopamine 2-20 mcg/kg/min 400mg in 250 D5W
Dobutamine 2-20 mcg/kg/min 250mg in 250 mg D5W
Epinephrine 0.1-1 mcg/kg/min 1mg in 250 D5W

Causes of non-response to vasopressors[10]

Push Dose Pressors

  • Use for temporary BP or CO boost
    • Post-intubation hypotension
    • Propofol-induced hypotension
    • A-fib with hypotension
      • Easier to convert well-perfused heart
  • Retrospective review of push-dose phenylephrine showed improved early hemodynamic stability but increased ICU mortality[11]
  • While epinephrine and phenylephrine are most commonly used, push dose vasopressin [12] and norepinephrine [13] are reasonable alternatives

Epinephrine

  • α1, α2, β1, β2 effects
  • Inopressor
  • Increases heart rate and inotropy and vasoconstricts
  • 10 cc syringe with 9 cc of NS and draw up 1 mL of 1:10,000 epi (cardiac epinephrine with 10mL of 100 mcg/mL which is 1 mg of epinephrine)
    • Now have 10mL of 10mcg/mL (1:100,000)
      • Use 0.5-2mL (5-20 mcg) every 1-5min (similar to epinephrine drip)
      • Can give peripherally since similar concentrations are give subcutaneously with lidocaine with epinephrine (1:100,000)
  • Onset - 1min
  • Duration - 10min
  • Effects are usually gone within 5 minutes

Phenylephrine

  • Pure α (no effect on heart) potent vasoconstrictor
  • Useful in tachycardic patient since no effect on HR and might even decrease from reflex parasympathetic response
  • Increase in heart perfusion can improve cardiac output
  • Place 1mL of 10mg/mL vial in 100mL NS
    • Now have 100mcg/mL with total bag containing 10 mg of phenylephrine
    • Draw up 10mL from bag with syringe
    • Use 0.5-2mL (50-200mcg) every 1-5 minutes
      • Can give peripherally since drug is approved for IM or SQ use
  • Onset - 1min
  • Duration - 20min
  • Effects are usually gone within 5 minutes

Extravasation Injury

  • Classically norepinephrine drips
  • Avoid hand/wrist and ensure peripheral IV quality before starting vasopressors
  • May occur with IO placements as well
  • Push dose epinephrine and phenylephrine have low chance of causing extravasation injury
  • Dermal necrosis[14]:
    • Prevention - phentolamine mesylate 10mg into each liter of norepinephrine solution (pressor effect is not changed)
  • Treatment ([15])
  1. If the pt is relying on the agent for their hemodynamics, switch the pressor to another IV or place an immediate IO or central line
  2. Do not discontinue the IV
  3. Aspirate as much residual as you can
  4. Administer subcutaneous phentolamine mesylate (Regitine) using 25 G or smaller needle
    • Place 5 mg (1 ml) in 9 ml of NS
    • A dose of 0.1 to 0.2 mg/kg (up to a maximum of 10 mg) should then be injected through the catheter and subcutaneously around the site
    • Administered as soon as the extravasation is detected, even if the area initially looks just a little white or OK
    • Should see near-immediate effects; otherwise consider an additional dose
    • Discontinue the IV/catheter
    • May cause systemic hypotension (but they should be on pressors at another site)
  5. Consult plastic surgery

See Also

External Links

References

  1. Plöchl, W, D J Cook, T A Orszulak, and R C Daly. 1998. Critical cerebral perfusion pressure during tepid heart operations in dogs. The Annals of thoracic surgery, no. 1. http://www.ncbi.nlm.nih.gov/pubmed/9692450
  2. Bellomo, Rinaldo, Li Wan, and Clive May. 2008. Vasoactive drugs and acute kidney injury. Critical care medicine, no. 4 Suppl. doi:10.1097/CCM.0b013e318169167f. http://www.ncbi.nlm.nih.gov/pubmed/18382191.
  3. Ricard JD. et al. Central or peripheral catheters for initial venous access of ICU patients: a randomized controlled trial. Crit Care Med. 2013 Sep;41(9):2108-15
  4. Chen J. et al. Extravasation injury associated with low-dose dopamine. Ann Pharmacother. 1998 May;32(5):545-8
  5. https://www.ncbi.nlm.nih.gov/pubmed/8449087
  6. Edmund H. Sonnenblick, M.D., William H. Frishman, M.D., and Thierry H. LeJemtel, M.D. Dobutamine: A New Synthetic Cardioactive Sympathetic Amine
  7. 7.0 7.1 De Backer Daniel et al. Comparison of Dopamine and Norepinephrine in the Treatment of Shock. NEJM 363(9). 779-789
  8. https://www.ncbi.nlm.nih.gov/pubmed/15542956
  9. Pasin L et al. Methylene blue as a vasopressor: a meta-analysis of randomised trials. Crit Care Resusc. 2013 Mar;15(1):42-8.
  10. Anand Swaminathan, "Occult Causes of Non-Response to Vasopressors", REBEL EM blog, July 13, 2017. Available at: https://rebelem.com/occult-causes-of-non-response-to-vasopressors/.
  11. Hawn JM, Bauer SR, Yerke J, et al. Effect of phenylephrine push prior to continuous infusion norepinephrine in patients with septic shock [published online ahead of print, 2020 Dec 11]. Chest. 2020;S0012-3692(20)35353-8. doi:10.1016/j.chest.2020.11.051
  12. Nowadly CD, Catlin JR, Fontenette RW. Push-Dose Vasopressin for Hypotension in Septic Shock. J Emerg Med. 2020;58(2):313-316. doi:10.1016/j.jemermed.2019.12.026
  13. Onwochei, Desire N. MBBS BSc (Hons), FRCA*; Ngan Kee, Warwick D. MBChB, MD, FANZCA, FHKCA†; Fung, Lillia MD, FRCPC*; Downey, Kristi MSc*; Ye, Xiang Y. MSc‡; Carvalho, Jose C. A. MD, PhD, FANZCA, FRCPC*. Norepinephrine Intermittent Intravenous Boluses to Prevent Hypotension During Spinal Anesthesia for Cesarean Delivery: A Sequential Allocation Dose-Finding Study. Anesthesia & Analgesia: July 2017 - Volume 125 - Issue 1 - p 212-218 doi: 10.1213/ANE.0000000000001846
  14. Phentolamine Mysylate for Injection - Dosage and Administration. http://www.rxlist.com/phentolamine-mesylate-for-injection-drug/indications-dosage.htm.
  15. Scott Weingart. Podcast 107 – Peripheral Vasopressor Infusions and Extravasation. EMCrit Blog. Published on September 16, 2013. Accessed on February 16th 2020. Available at https://emcrit.org/emcrit/peripheral-vasopressors-extravasation/