Vasopressors in Septic Shock

Critical Care / ICU

💉 Vasopressors in Septic Shock

A PharmD reference for vasopressor selection, dosing, and escalation in septic shock. Based on the 2021 SSC guidelines and current evidence. Covers norepinephrine first-line use, vasopressin add-on, dopamine exceptions, and emerging agents.

📋 Printable Quick Card →

First-Line: Norepinephrine

Parameter	Details
Mechanism	Alpha-1 >> beta-1 agonist. Increases SVR (vasoconstriction) with modest inotropy.
Dose range	0.01–3 mcg/kg/min IV infusion (typical effective dose 0.1–0.5 mcg/kg/min)
Target	MAP ≥65 mmHg (individualize; some patients, esp. with chronic HTN, may need MAP 70–80)
Access	Central line preferred; peripheral administration for short periods (≤6h) is acceptable in emergencies via large bore IV in proximal vein
SSC 2021 recommendation	Strong recommendation, moderate-quality evidence, first-line vasopressor for septic shock

Add-on Agents (when NE > 0.25–0.5 mcg/kg/min)

Agent	Role	Dose	Evidence
Vasopressin	NE-sparing; add early (NE ≥0.25 mcg/kg/min)	Fixed dose 0.03–0.04 units/min (not titrated)	VASST: no mortality benefit overall; post-hoc benefit in less severe shock. SSC 2021: weak recommendation (suggest adding), moderate-quality evidence.
Epinephrine	Refractory shock; also used for anaphylaxis	0.01–0.5 mcg/kg/min; titrate to MAP	May cause lactic acidosis (beta-2 mediated); monitor lactate carefully
Angiotensin II (Giapreza)	High-renin phenotype; refractory shock	Starting dose 20 ng/kg/min; titrate 0–80 ng/kg/min	ATHOS-3: ↑MAP responder rate vs. placebo in high-dose vasopressor patients; expensive, limited availability
Dopamine	Not preferred; consider in bradycardia or low cardiac output phenotype only	2–20 mcg/kg/min	↑ arrhythmia risk vs. NE (De Backer et al., NEJM 2010). SSC 2021: weak recommendation against use in most patients.

Adjunct: Hydrocortisone

Consider adding IV hydrocortisone in refractory septic shock (vasopressor-dependent despite adequate resuscitation):

Parameter	Details
Threshold	NE or equivalent ≥0.25 mcg/kg/min for ≥4 hours despite adequate fluids
Dose	Hydrocortisone 200 mg/day IV, either 50 mg q6h or 200 mg continuous infusion
Evidence	APROCCHSS and ADRENAL trials: faster vasopressor weaning; no clear mortality benefit in ADRENAL; mortality benefit in APROCCHSS (with fludrocortisone). SSC 2021: weak recommendation.
Duration	Wean when vasopressors no longer required; typical 5–7 day course

PharmD Clinical Pearls

💡 Phenylephrine is a pure alpha agonist with no inotropy. Avoid in septic shock (reduced cardiac output in patients who are already vasodilated may worsen organ perfusion). It has a role in vasoplegic shock post-cardiac surgery.

💡 Vasopressin should be added at a fixed dose (0.03 units/min), not titrated like NE. Think of it as an add-on steroid for vascular tone, not a primary vasopressor.

💡 The CENSER trial showed early low-dose norepinephrine (within 1h of septic shock diagnosis) improved shock control vs. standard care. Advocate for early vasopressor initiation rather than waiting for fluid resuscitation to fail.

💡 Dopamine-mediated renal protection is a myth. "Renal dose" dopamine does not prevent AKI and is not recommended. Adequate MAP and cardiac output are the actual renal protection strategies.

🎓

Reviewed by a licensed pharmacist

Reference content reviewed for clinical accuracy. This is not a substitute for institutional protocols or professional judgment.

← Back to Clinical Reference · Literature Archive →