Vasopressors

(Redirected from Push dose pressors)

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

Vasopressors may be initiated peripherally while central access is being obtained — do not delay for central line placement (SSC 2021).[5]

Pressor Initial Dose Max Dose Cardiac Effect BP Effect Arrhythmias Special Notes
Dobutamine 2-5 mcg/kg/min 20 mcg/kg/min (up to 40 in refractory cases)[6] Strong β₁ agonist (+inotrope, +chronotrope); weak β₂ agonist (+vasodilation) Minimal α effect; may decrease BP due to β₂ vasodilation Variable HR effects; can cause tachycardia Indicated in decompensated systolic CHF and cardiogenic shock with adequate BP. Not a vasopressor — it is an inotrope. Must be used with a vasopressor if hypotensive.
Dopamine 2-5 mcg/kg/min 20 mcg/kg/min β₁ and endogenous norepinephrine release Mixed α and β effects at all doses; α effects predominate at higher doses Arrhythmogenic from β₁ effects More adverse events (especially arrhythmia) when used in shock compared to norepinephrine[7]. SSC 2021 suggests against dopamine as first-line except in select patients with bradycardia and low risk of tachyarrhythmia.
Epinephrine 1-10 mcg/min (0.01-0.1 mcg/kg/min) 0.5 mcg/kg/min +Inotropy, +chronotropy (β₁) Low dose: β₂ vasodilation may predominate; high dose: α₁ vasoconstriction predominates Significant — tachycardia, SVT, VT. Increases myocardial O₂ demand. 2nd or 3rd line for septic shock (SSC 2021: add after norepinephrine ± vasopressin). 1st line for anaphylaxis (0.3-0.5 mg IM) and cardiac arrest. May cause splanchnic vasoconstriction, lactic acidosis, and hyperglycemia.
Norepinephrine 2-5 mcg/min (0.01-0.03 mcg/kg/min) 0.5-1 mcg/kg/min (some sources up to 3.3 mcg/kg/min)[8] Mild β₁ direct effect (+inotropy) Strong α₁ and α₂ vasoconstriction; β₁ effect Less arrhythmogenic than dopamine[7] 1st line for septic shock (SSC 2021)[5]. Increases MAP primarily via vasoconstriction. Increases coronary perfusion pressure. Minimal β₂ effect.
Milrinone 50 mcg/kg IV over 10 min (loading dose often omitted in acute illness due to hypotension risk) 0.375-0.75 mcg/kg/min PDE-3 inhibitor → ↑intracellular cAMP → ↑Ca²⁺ influx → +inotropy Arteriolar and venous vasodilator (reduces preload AND afterload) Less arrhythmogenic than dobutamine Inodilator — useful in decompensated HF with elevated afterload, RV failure, or pulmonary hypertension. Causes hypotension — not a vasopressor; use with a vasopressor if MAP is low. Renally cleared — dose-reduce in CKD.
Phenylephrine 100-180 mcg/min, then 40-60 mcg/min 0.4-9.1 mcg/kg/min No direct cardiac effect Pure α₁ agonist → vasoconstriction May cause reflex bradycardia Short duration of action (5-20 min IV). Use in septic shock only if: NE causes arrhythmias, cardiac output is high with persistent hypotension, or as salvage when NE + vasopressin have failed.[5]
Vasopressin 0.03 U/min (fixed dose) 0.04 U/min No direct inotropic or chronotropic effect; possible reflex bradycardia V₁ receptor agonist → vascular smooth muscle constriction Minimal 2nd line in septic shock — add to NE rather than escalating NE (SSC 2021 suggests adding before epinephrine)[5]. Fixed dose — generally not titrated. May reduce the risk of atrial fibrillation vs. catecholamine-only regimens.[9] Avoid dose >0.04 U/min → risk of cardiac and mesenteric ischemia.
Methylene blue[10] IV bolus 1-2 mg/kg over 15 min 1-2 mg/kg/hour (limited data on max duration) Possible increased inotropy; improves cardiac ATP utilization Inhibits NO-mediated peripheral vasodilation → increases SVR Minimal reported Salvage therapy for refractory vasodilatory shock unresponsive to catecholamines. Contraindicated in G6PD deficiency (hemolytic anemia), ARDS, severe pulmonary hypertension. Interferes with pulse oximetry readings (falsely low SpO₂). Avoid with serotonergic drugs (risk of serotonin syndrome).
Angiotensin II (Giapreza) 20 ng/kg/min 40-80 ng/kg/min (max 200 ng/kg/min per label) No direct cardiac effect AT₁ receptor agonist → potent arteriolar vasoconstriction; also stimulates aldosterone secretion Minimal Salvage therapy for refractory vasodilatory shock (ATHOS-3 trial)[11]. May be particularly useful in patients on ACEi/ARB or with high renin states. Monitor for thrombosis (increased risk reported).
Medication IV Dose (mcg/kg/min) Standard Concentration Final Concentration
Norepinephrine (Levophed) 0.01-2 mcg/kg/min 8 mg in 500 mL D5W 16 mcg/mL
Dopamine 2-20 mcg/kg/min 400 mg in 250 mL D5W 1,600 mcg/mL
Dobutamine 2-20 mcg/kg/min 250 mg in 250 mL D5W 1,000 mcg/mL
Epinephrine 0.01-1 mcg/kg/min 1 mg in 250 mL D5W 4 mcg/mL

Norepinephrine 2-5 mcg/min (0.01-0.03 mcg/kg/min), max 0.5-1 mcg/kg/min IV drip — 1st line for septic shock (SSC 2021) Epinephrine 1-10 mcg/min (0.01-0.1 mcg/kg/min), max 0.5 mcg/kg/min IV drip — 1st line for anaphylaxis and cardiac arrest Vasopressin 0.03 U/min (fixed dose), max 0.04 U/min IV drip — Add to NE rather than escalating NE (SSC 2021) Dopamine 2-5 mcg/kg/min, max 20 mcg/kg/min IV drip — SSC 2021 suggests against as 1st line; more arrhythmogenic than NE Dobutamine 2-5 mcg/kg/min, max 20 mcg/kg/min IV drip — Inotrope, not a vasopressor; use with vasopressor if hypotensive Phenylephrine 100-180 mcg/min, then 40-60 mcg/min IV drip — Pure alpha-1 agonist; short duration 5-20 min Milrinone 0.375-0.75 mcg/kg/min (loading often omitted) IV drip — Inodilator; causes hypotension; useful in RV failure/pulmonary HTN Methylene blue 1-2 mg/kg IV bolus over 15 min IV — Salvage for refractory vasodilatory shock; contraindicated in G6PD deficiency Angiotensin II (Giapreza) 20 ng/kg/min, max 40-80 ng/kg/min IV drip — Salvage for refractory vasodilatory shock (ATHOS-3 trial)

Causes of non-response to vasopressors[12]

Push (Bolus) Dose Pressors

  • Use for temporary BP or CO boost with no evidence for improved patient outcome
    • 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[13]
  • While epinephrine and phenylephrine are most commonly used, push dose vasopressin [14] and norepinephrine [15] 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[16]:
    • Prevention - phentolamine mesylate 10mg into each liter of norepinephrine solution (pressor effect is not changed)
  • Treatment ([17])
  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


Medication Dosing

Norepinephrine 0.05-0.4mcg/kg/min (start 5-15mcg/min) IV Epinephrine 0.01-0.5mcg/kg/min IV Vasopressin 0.03-0.04 units/min (fixed dose, do not titrate) IV Dopamine 2-20mcg/kg/min IV Phenylephrine 100-180mcg/min (0.4-9.1mcg/kg/min) IV Dobutamine 2-20mcg/kg/min IV

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. ↑ 5.0 5.1 5.2 5.3 Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021;49(11):e1063-e1143.
  6. ↑ Unverferth DV, Blanford M, Kates RE, Leier CV. Tolerance to dobutamine after a 72 hour continuous infusion. Am J Med. 1980;69(2):262-6.
  7. ↑ 7.0 7.1 De Backer D, et al. Comparison of Dopamine and Norepinephrine in the Treatment of Shock. NEJM. 2010;363(9):779-789.
  8. ↑ Martin C, Papazian L, Perrin G, et al. Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest. 1993;103(6):1826-31.
  9. ↑ McIntyre WF, et al. Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock. JAMA. 2018;319(18):1889.
  10. ↑ Pasin L, et al. Methylene blue as a vasopressor: a meta-analysis of randomised trials. Crit Care Resusc. 2013;15(1):42-8.
  11. ↑ Khanna A, et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017;377(5):419-430.
  12. ↑ 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/.
  13. ↑ 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
  14. ↑ 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
  15. ↑ 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
  16. ↑ Phentolamine Mysylate for Injection - Dosage and Administration. http://www.rxlist.com/phentolamine-mesylate-for-injection-drug/indications-dosage.htm.
  17. ↑ 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/
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