Vasopressor Dilution & Dosing Guide

Why Vasopressors Work — The Physiology

Blood pressure = Cardiac Output × Systemic Vascular Resistance (MAP = CO × SVR). In septic shock, the primary problem is ↓ SVR (massive vasodilation from nitric oxide, prostaglandins, cytokines). The heart is initially hyperdynamic (↑ CO) trying to compensate. Vasopressors restore SVR and therefore MAP, ensuring perfusion pressure to vital organs.

The adrenoreceptor system is the target:

Receptor	Location	Effect	Clinical Result
α₁	Vascular smooth muscle	Vasoconstriction	↑ SVR → ↑ MAP
β₁	Heart (SA node, myocardium)	↑ HR, ↑ contractility	↑ CO, ↑ HR, ↑ myocardial O₂ demand
β₂	Vasculature, bronchi	Vasodilation, bronchodilation	↓ SVR, bronchodilation
V₁ (AVP receptor)	Vascular smooth muscle	Vasoconstriction (non-catecholamine)	↑ SVR without cardiac stimulation

Why Noradrenaline First?

Noradrenaline is predominantly α₁ (vasoconstriction) with mild β₁ (minimal HR increase). In septic shock, we want ↑ SVR without excessive tachycardia (which increases myocardial O₂ demand). Dopamine causes more arrhythmias and has unpredictable dose-receptor relationships. SOAP II trial confirmed NE superiority.

Ideal Body Weight (IBW) — Always Use for Dosing

Vasopressor doses are calculated per kg of Ideal Body Weight, not actual body weight. In obese patients, using actual weight will overdose and cause peripheral ischaemia.

IBW Formula (Devine Formula)

Males: IBW (kg) = 50 + 2.3 × (Height in inches − 60)

Females: IBW (kg) = 45.5 + 2.3 × (Height in inches − 60)

Quick metric conversion: Height in cm ÷ 2.54 = Height in inches
Male example: Height 170 cm = 67 inches → IBW = 50 + 2.3×(67−60) = 50 + 16.1 = 66 kg
Female example: Height 155 cm = 61 inches → IBW = 45.5 + 2.3×(61−60) = 45.5 + 2.3 = 47.8 kg

Bedside shortcut: Male IBW ≈ Height(cm) − 100 | Female IBW ≈ Height(cm) − 105

The Universal Dose Calculation Formula

Infusion Rate Formula (applies to ALL vasopressors)

Rate (ml/hr) = [Dose (mcg/kg/min) × Weight (kg) × 60] ÷ Concentration (mcg/ml)

Where:
Dose = desired dose in mcg/kg/min
Weight = IBW in kg
60 = converts minutes to hours
Concentration = mcg per ml of your prepared solution

Example — Noradrenaline 0.1 mcg/kg/min for 60 kg patient, concentration 40 mcg/ml:
Rate = (0.1 × 60 × 60) ÷ 40 = 360 ÷ 40 = 9 ml/hr

Rule of 6 (Quick Mental Math at Bedside)

Prepare drug so that: 6 × body weight (mg) in 100 ml → 1 ml/hr = 1 mcg/kg/min. Example: 60 kg patient → put 360 mg drug in 100 ml → 1 ml/hr = 1 mcg/kg/min. Used for dopamine and dobutamine in many ICUs. Not suitable for all drugs — check concentration limits.

Noradrenaline (Norepinephrine)

The Drug — What's in the Ampoule

🔬 Ampoule Composition

Available as: Noradrenaline bitartrate
Concentration: 2 mg/2 ml (1 mg/ml) or 4 mg/4 ml
Active drug: 1 mg noradrenaline base per 2 mg bitartrate salt
pH: 3.0–4.5 (acidic — incompatible with alkaline solutions)
Storage: Protect from light; discard if brown discolouration

🧪 Standard Dilution (Syringe Pump)

Standard: 4 mg in 46 ml NS = 80 mcg/ml
Concentrated: 8 mg in 42 ml NS = 160 mcg/ml (for fluid-restricted patients)
High-dose (refractory): 16 mg in 34 ml NS = 320 mcg/ml
Diluent: 0.9% NaCl or D5W — NOT Ringer's Lactate (alkaline — causes precipitation)

Dose Calculation Table (80 mcg/ml standard solution)

Dose (mcg/kg/min)	50 kg patient (ml/hr)	60 kg patient (ml/hr)	70 kg patient (ml/hr)	80 kg patient (ml/hr)
0.05 (starting)	1.9	2.3	2.6	3.0
0.1 (usual start)	3.8	4.5	5.3	6.0
0.2	7.5	9.0	10.5	12.0
0.3	11.3	13.5	15.8	18.0
0.5	18.8	22.5	26.3	30.0
1.0 (high dose)	37.5	45.0	52.5	60.0

Parameter	Details
Receptors	α₁+++ (dominant), β₁+ (minor)
Starting dose	0.05–0.1 mcg/kg/min
Usual range	0.1–0.5 mcg/kg/min
High dose	>0.5 mcg/kg/min (consider adding vasopressin)
Maximum	No absolute ceiling; >1 mcg/kg/min = refractory shock
Indication	First-line: ALL distributive shock (septic, anaphylactic, neurogenic)
Peripheral line	Acceptable for up to 12h in emergency (antecubital/wrist); inspect q30 min for extravasation
Extravasation antidote	Phentolamine 5–10 mg in 10 ml NS — infiltrate subcutaneously around site

🇮🇳 Indian Brand Names & Availability

Noradrenaline is available as: Levophed (Abbott), Norad, Epsilor. Most come as 4 mg/4 ml ampoules. Always confirm concentration on the ampoule — a 2 mg/ml preparation requires different dilution calculations.

Vasopressin (ADH / AVP)

🔬 Ampoule Composition

Available as: Arginine Vasopressin (AVP) 20 IU/ml ampoule (1 ml)
Mechanism: Acts on V₁ receptors on vascular smooth muscle → vasoconstriction via IP₃/DAG pathway (NOT catecholamine dependent)
Why useful in shock: Catecholamine-depleted states (prolonged septic shock) see relative vasopressin deficiency — replacing it restores vascular tone without tachycardia

🧪 Standard Dilution

Standard: 20 IU (1 ampoule) in 19 ml NS = 1 IU/ml
Alternative: 40 IU (2 ampoules) in 38 ml NS = 1 IU/ml
Infusion rate: 0.03 IU/min = 1.8 ml/hr (fixed dose — do NOT titrate)
Maximum: 0.03–0.04 IU/min (higher doses cause mesenteric/coronary ischaemia)

Parameter	Details
Dose	FIXED 0.03 U/min — NEVER titrated (unlike catecholamines)
When to add	Noradrenaline >0.25 mcg/kg/min AND MAP still <65 mmHg
Goal	Catecholamine-sparing (allows NE dose reduction); reduces arrhythmia risk
Infusion rate	1.8 ml/hr if prepared as 1 IU/ml solution
Side effects	Mesenteric ischaemia (at >0.04 IU/min), hyponatraemia (ADH effect), skin necrosis
Contraindication	Do NOT use in cardiogenic shock — no cardiac output benefit and worsens afterload

Adrenaline (Epinephrine)

🔬 Ampoule Composition

Available as: 1 mg/ml (1:1000) or 0.1 mg/ml (1:10,000)
For ICU infusion: Use 1 mg/ml ampoules
For anaphylaxis IM: 1:1000 (1 mg/ml) — 0.5 mg = 0.5 ml IM
For cardiac arrest: 1 mg IV (1 ml of 1:1000 or 10 ml of 1:10,000)

🧪 ICU Infusion Dilution

Standard: 5 mg (5 ampoules 1mg/ml) in 45 ml NS = 100 mcg/ml
Starting dose: 0.05–0.1 mcg/kg/min
Usual range: 0.1–0.5 mcg/kg/min
Note: Raises lactate (β₂ mediated glycogenolysis) — do NOT use lactate clearance to guide treatment when on adrenaline infusion

Indication	Route	Dose	Notes
Anaphylaxis	IM (anterolateral thigh)	0.5 mg (0.5 ml of 1:1000) — adults; 0.3 mg children	FIRST LINE — do before anything else. Repeat q5–15 min if needed.
Cardiac arrest (ACLS)	IV/IO	1 mg q3–5 min	Give early in non-shockable rhythms (PEA/asystole)
Refractory septic shock	IV infusion	0.05–0.5 mcg/kg/min	Add to/replace NE when NE >0.5 + vasopressin fails
Post-extubation stridor	Nebuliser	1 mg (1 ml of 1:1000) in 4 ml NS	Local mucosal vasoconstriction; lasts ~30–60 min
Bradycardia with pulse	IV infusion	2–10 mcg/min	While preparing for pacing

Dobutamine

🔬 Ampoule Composition

Available as: 250 mg/20 ml (12.5 mg/ml)
Mechanism: Predominantly β₁ agonist → ↑ contractility + ↑ HR; β₂ → peripheral vasodilation. Net effect: ↑ CO, ↓ SVR, ↑ HR.
Key concept: Dobutamine is an inotrope, not a vasopressor. It LOWERS blood pressure in isolation. Always combine with NE in cardiogenic shock with hypotension.

🧪 Standard Dilution

Standard: 250 mg in 250 ml NS = 1000 mcg/ml (1 mg/ml)
Or: 500 mg in 250 ml NS = 2000 mcg/ml
Starting dose: 2.5–5 mcg/kg/min
Usual range: 5–15 mcg/kg/min
Max: 20 mcg/kg/min (beyond this: tachycardia outweighs benefit)

Dose Calculation (1000 mcg/ml solution)

Formula

Rate (ml/hr) = [Dose (mcg/kg/min) × IBW (kg) × 60] ÷ 1000

Example: 5 mcg/kg/min for 60 kg patient using 1000 mcg/ml solution:
Rate = (5 × 60 × 60) ÷ 1000 = 18,000 ÷ 1000 = 18 ml/hr

10 mcg/kg/min: 36 ml/hr | 15 mcg/kg/min: 54 ml/hr

Indication	Dose	Notes
Cardiogenic shock + adequate BP	5–10 mcg/kg/min	Improves CO; may drop BP — have NE ready
Septic cardiomyopathy (ScvO₂ <65%, low echo EF)	5–10 mcg/kg/min	Add to NE when CO component identified
Acute decompensated heart failure	2.5–5 mcg/kg/min	Short-term bridge to definitive therapy

Do NOT use Dobutamine alone in Hypotension

Dobutamine's β₂ activity causes peripheral vasodilation, which LOWERS MAP. In a hypotensive patient, always add noradrenaline first to maintain vascular tone, then add dobutamine for inotropy.

Dopamine — Use with Caution

🔬 Ampoule Composition

Available as: 200 mg/5 ml (40 mg/ml) or 400 mg/5 ml
Dose-receptor relationship:
• Low (1–5 mcg/kg/min): DA₁ receptor → renal/splanchnic vasodilation
• Medium (5–10 mcg/kg/min): β₁ → ↑ CO, ↑ HR
• High (>10 mcg/kg/min): α₁ → vasoconstriction
Problem: These "zones" are unreliable — significant overlap exists

🧪 Dilution

Standard: 200 mg in 50 ml = 4000 mcg/ml (4 mg/ml)
Or: 400 mg in 250 ml NS = 1600 mcg/ml
Starting: 2–5 mcg/kg/min; titrate up to 20 mcg/kg/min
Note: "Renal-dose dopamine" (1–3 mcg/kg/min) does NOT protect kidneys — DOPAMINE-RCT proved no benefit

SOAP II Trial — Why Dopamine is Avoided

SOAP II (De Backer et al., NEJM 2010): Dopamine vs Noradrenaline in 1679 patients with shock. Dopamine caused significantly more arrhythmias (24% vs 12%) and higher 28-day mortality in cardiogenic shock subgroup. SSC 2021: Do NOT use dopamine as first-line vasopressor. Use only when NE is unavailable.

Phenylephrine

🔬 Ampoule Composition

Available as: 10 mg/ml (various concentrations)
Mechanism: Pure α₁ agonist — NO β effects whatsoever
Effect: Pure vasoconstriction → ↑↑ SVR → reflex bradycardia (via baroreceptors) → may reduce CO
Niche use: Septic shock + tachyarrhythmia where NE worsens rate; post-spinal hypotension

🧪 Dilution

Bolus (OR/spinal hypotension): 100 mcg IV bolus (dilute 1 mg in 10 ml = 100 mcg/ml)
Infusion: 10 mg in 250 ml NS = 40 mcg/ml
Infusion rate: 0.5–5 mcg/kg/min
Avoid in: Left ventricular failure (↑ afterload worsens cardiac output)

Shock Management Algorithm

Step-by-Step: Septic Shock (most common — 50% of ICU admissions)

Step 1 — Identify & resuscitate simultaneously: Blood cultures × 2 → Antibiotics within 1h → Crystalloid 30 ml/kg → Check lactate
Step 2 — Start Noradrenaline if MAP <65 despite 500 ml fluid bolus. Start at 0.1 mcg/kg/min. Titrate by 0.05 mcg/kg/min every 5–10 min to MAP ≥65.
Step 3 — If NE >0.25 mcg/kg/min: Add Vasopressin 0.03 U/min (FIXED). This is catecholamine-sparing — often allows NE dose reduction.
Step 4 — If still refractory: Add Adrenaline 0.1 mcg/kg/min OR Hydrocortisone 200 mg/day (if not started already)
Step 5 — Assess cardiac function (POCUS echo): If EF low + cold extremities + ScvO₂ <65% → Add Dobutamine 5–10 mcg/kg/min
Step 6 — Refractory vasoplegia: Methylene Blue 1–2 mg/kg IV over 20 min (inhibits iNOS → ↑ SVR); Angiotensin II if available

Type of Shock	CO	SVR	First Drug	Add-On
Distributive (Septic)	↑ or N	↓↓	Noradrenaline	Vasopressin → Adrenaline → Hydrocortisone
Cardiogenic	↓↓	↑↑	Noradrenaline + Dobutamine	Levosimendan; VA-ECMO if refractory
Hypovolaemic	↓	↑↑	IV Fluids (1st!)	NE only as bridge to source control; stop bleeding
Anaphylactic	↑	↓↓	Adrenaline 0.5 mg IM IMMEDIATELY	IV fluids; NE infusion if IM adrenaline insufficient
Neurogenic	N or ↓	↓↓	Noradrenaline or Phenylephrine	Atropine for bradycardia component
Obstructive (tension PTX)	↓	↑	Needle decompression IMMEDIATELY	Fluids; vasopressors as temporary bridge only

Clinical Pearls

💡 Pearl 1 — Arterial Line First

Always insert an arterial line when starting vasopressors. Non-invasive BP is unreliable in shock — cuff readings underestimate MAP by 10–20 mmHg. Wrist (radial) artery is quickest. Allen's test first.

💡 Pearl 2 — Peripheral Vasopressors Are OK Short-Term

In emergency: start NE peripherally (antecubital fossa or wrist with 18G IV). Acceptable for up to 12h. Check site every 30 min for blanching/swelling. Have phentolamine ready for extravasation.

💡 Pearl 3 — Lactate Tells More Than MAP

MAP ≥65 mmHg does NOT mean the patient is perfused. Check lactate every 2h. Lactate clearance ≥10% per 2h = adequate resuscitation. Persistent lactate despite MAP = occult hypoperfusion (mesenteric, microcirculatory).

💡 Pearl 4 — Adrenaline Raises Lactate

Adrenaline's β₂ receptor activation stimulates hepatic glycogenolysis → raises blood glucose AND lactate. Do NOT use lactate to monitor resuscitation in patients on adrenaline. Use ScvO₂ or Echo instead.

💡 Pearl 5 — Vasopressin = Fixed Dose

Unlike all other vasopressors, vasopressin is NEVER titrated. Always 0.03 U/min fixed dose. Higher doses cause catastrophic mesenteric and coronary ischaemia. The benefit is catecholamine-sparing, not dose-response.

💡 Pearl 6 — Don't Chase Normal MAP in Elderly

Elderly hypertensive patients need higher MAP to perfuse autoregulated organs (brain, kidney). Target MAP 70–75 mmHg in known hypertensives — SEPSISPAM trial showed reduced AKI with higher MAP in this group.

💡 Pearl 7 — Cold Peripheries = Add Dobutamine

Mottled extremities + capillary refill >3s + ScvO₂ <65% despite adequate MAP = cardiac output problem (septic cardiomyopathy in 30–50%). POCUS: check EF. If low → dobutamine 5 mcg/kg/min.

💡 Pearl 8 — Methylene Blue Caution

NEVER give methylene blue to patients on SSRIs, SNRIs, MAOIs, fentanyl, or tramadol — fatal serotonin syndrome. Also check for G6PD deficiency before use (causes haemolysis).

Common Mistakes

❌ Mistake 1

Using actual body weight for vasopressor dose in obese patients. A 100 kg man at 165 cm has IBW of 67 kg. Using 100 kg will give 50% overdose → tachycardia, arrhythmia, digital ischaemia.

❌ Mistake 2

Diluting noradrenaline in Ringer's Lactate. RL is alkaline (pH 6.5–7.5). Catecholamines are oxidised in alkaline solutions — forms brown discolouration = drug degradation = loss of potency. Use 0.9% NaCl or D5W only.

❌ Mistake 3

Not titrating vasopressors to lactate clearance. Targeting MAP alone is insufficient. Achieve MAP ≥65 AND lactate clearance ≥10% per 2h. Persistent lactaemia despite MAP = occult hypoperfusion needing further intervention.

❌ Mistake 4

Adding dobutamine without a vasopressor in hypotensive cardiogenic shock. Dobutamine drops SVR via β₂ effects → BP falls further. Establish MAP ≥65 with NE first, then add dobutamine for CO support.

❌ Mistake 5

Titrating vasopressin dose. Vasopressin is prescribed at 0.03 U/min only — fixed. Increasing dose to "0.05" or "0.06" causes severe mesenteric ischaemia and digital gangrene. It is not a titratable drug.

❌ Mistake 6

Giving adrenaline IV instead of IM in anaphylaxis. IM adrenaline (anterolateral thigh) has faster, safer onset than IV in a non-arrested patient. IV adrenaline in a non-arrested patient causes hypertensive crisis and VT/VF.

Exam Pearls (DrNB / PDCC / IFCCM)

Q: First-line vasopressor in septic shock? → Noradrenaline (SSC 2021, Grade 1B)

Q: When do you add vasopressin? → When NE dose exceeds 0.25 mcg/kg/min. Dose = 0.03 U/min (FIXED, never titrated)

Q: Why not dopamine in septic shock? → SOAP II trial: more arrhythmias (24% vs 12%), worse mortality in cardiogenic subgroup. SSC 2021: weak recommendation against dopamine.

Q: MAP target in septic shock? → 65 mmHg (SEPSISPAM trial: higher target 80–85 only reduced need for RRT in hypertensives, no overall mortality benefit)

Q: What is "renal dose dopamine"? → A myth. No RCT shows renal protection. DOPAMINE-RCT proved no benefit. SSC recommends AGAINST low-dose dopamine for renal protection.

Q: Vasopressor for anaphylaxis? → IM Adrenaline 0.5 mg (1:1000) into anterolateral thigh. NOT IV unless cardiac arrest. NOT antihistamine first.

Q: IBW formula for male, 170 cm? → 170 cm = 67 inches → 50 + 2.3 × (67−60) = 50 + 16.1 = 66.1 kg

Q: NE infusion rate for 0.1 mcg/kg/min in 60 kg patient using 80 mcg/ml solution? → (0.1 × 60 × 60) ÷ 80 = 360 ÷ 80 = 4.5 ml/hr

References

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.
De Backer D, Biston P, Devriendt J, et al. Comparison of Dopamine and Norepinephrine in the Treatment of Shock (SOAP II). N Engl J Med. 2010;362(9):779–789.
Russell JA, Walley KR, Singer J, et al. Vasopressin versus Norepinephrine in Septic Shock (VASST). N Engl J Med. 2008;358(9):877–887.
Asfar P, Meziani F, Hamel JF, et al. High versus Low Blood-Pressure Target in Septic Shock (SEPSISPAM). N Engl J Med. 2014;370(17):1583–1593.
Khanna A, English SW, Wang XS, et al. Angiotensin II for Vasodilatory Shock (ATHOS-3). N Engl J Med. 2017;377(5):419–430.
Myatra SN, et al. Indian Society of Critical Care Medicine Position Statement on Sepsis and Septic Shock. Indian J Crit Care Med. 2020;24(S1):S1–S28.
Marino PL. The ICU Book, 4th edition. Chapters 18–21: Circulatory Shock. Lippincott Williams & Wilkins; 2014.
Parrillo JE, Dellinger RP (eds). Critical Care Medicine: Principles of Diagnosis and Management in the Adult, 5th edition. Elsevier; 2019.
Hollenberg SM. Vasoactive Drugs in Circulatory Shock. Am J Respir Crit Care Med. 2011;183(7):847–855.