Noradrenaline (Norepinephrine) Intravenous Infusion for Adults

Who can administer

Administration RESTRICTED - see Appendix 1

Important information

Central line administration: administration by infusion in specialist units only- (Critical Care, CCU, ED resus)
Peripheral line administration (restricted use - Critical care, Outreach ONLY)
Doses given are in terms of noradrenaline BASE
For Y-site compatibility see below

Available preparations

Noradrenaline base 4mg in 50mL (80 micrograms per mL) solution for infusion (1st line for Central line administration)

Noradrenaline base 2mg per 2mL concentrate for solution for infusion (1:1000) (1st line for Peripheral line administration)

Other strengths also may be available - see Further Information

Reconstitution

Central line administration

Noradrenaline base 4mg in 50mL (80 micrograms per mL) solution for infusion: Already in solution
Ampoules (only) to be diluted further prior to administration (generally only used when the pre-made solution is unavailable, or when higher concentrations are required) (see Further Information re ampoules)
Use a 5 micron filter needle when drawing up contents of ampoule

Peripheral line administration (restricted use - see under Dose below)

Noradrenaline base 2mg per 2mL concentrate for solution for infusion
Dilute further prior to administration
Draw up using a 5 micron filter needle

Infusion fluids

Glucose 5% (preferred ^{(ref 1)}) or Sodium chloride 0.9%

Methods of intravenous administration

Continuous intravenous infusion (administer using an electronically controlled infusion device)

Central line administration

Using 4mg base in 50mL
Administer at a suitable rate, titrated to pressor effect observed- see under 'dose'
Higher concentrations may occasionally be used- see under Further Information

Peripheral line administration (restricted use - see under Dose below)

Noradrenaline base 2mg/2mL concentrate for solution for infusion (ampoules)
Prepare a solution containing 4mg in 250ml (16 micrograms per mL)
Administer at a suitable rate, titrated to response - see 'dose' below

Dose in adults

Continuous intravenous infusion - CENTRAL LINE: (Critical Care, CCU, ED resus)

Note: 4mg base in 50mL = 80 micrograms per mL^{(ref 1)}

There are two different ways of dosing noradrenaline for Central line use

Important note ^{(ref 3)}

If patient is of normal to high body weight, consider using Method 1 (STANDARD APPROACH)- to avoid inadvertent overdose
If patient is less than 50kg- consider using Method 2 (WEIGHT BASED APPROACH)

1: Method 1 (STANDARD APPROACH) ^{(ref 2)} - see Table 1 below

Rate expressed in micrograms/minute
Initial rate: 5 to 15 micrograms/minute, titrated to target blood pressure
Usual dose range: 2 to 80 micrograms/minute. Higher doses may be required.
Do not stop infusion suddenly as abrupt withdrawal can result in acute hypotension

Table 1 (STANDARD APPROACH) (Central line) Rate (mL/hr) of a 4mg in 50mL infusion using doses in micrograms/minute
Dosage (microgram/minute)	1	2	3	4	5	6	7	8	9	10	15	20	25	30	40	60	80mcg/min
4mg/50ml (rate in mL/hour)	0.75	1.5	2.3	3	3.8	4.5	5.3	6	6.8	7.5	11.3	15	18.8	22.5	30	45	60

Table 1 (STANDARD APPROACH) (Central line)

Rate (mL/hr) of a 4mg in 50mL infusion using doses in micrograms/minute

Dosage (microgram/minute)

80mcg/min

4mg/50ml (rate in mL/hour)

0.75

1.5

2.3

3.8

4.5

5.3

6.8

7.5

11.3

18.8

22.5

2: Method 2 (WEIGHT-BASED APPROACH) ^{(ref 2)}- see Table 2 below

Rate expressed in micrograms/kg/minute
Initial rate: 0.05 to 0.15 micrograms/kg/minute, titrated to target blood pressure
Usual dose range: 0.025 to 1 microgram/kg/minute
Do not stop infusion suddenly as abrupt withdrawal can result in acute hypotension

Table 2: (WEIGHT-BASED APPROACH) (Central line) Rate (ml/hr) of a 4mg in 50ml infusion using doses in micrograms/KG/minute
	Weight of patient in 10kg increments below (rate is given in mL/hour in this table)
Dose(microgram/kg/min)- below	30kg	40kg	50kg	60kg	70kg	80kg
0.025	0.6	0.8	0.9	1.1	1.3	1.5
0.05	1.1	1.5	1.9	2.3	2.6	3
0.1	2.3	3	3.8	4.5	5.3	6
0.15	3.4	4.5	5.6	6.8	7.9	9
0.2	4.5	6	7.5	9	10.5	12
0.25	5.6	7.5	9.4	11.3	13.1	15
0.3	6.8	9	11.3	13.5	15.8	18
0.35	7.9	10.5	13.1	15.8	18.4	21
0.4	9	12	15	18	21	24
0.45	10.1	13.5	16.9	20.3	23.6	27
0.5	11.3	15	18.8	22.5	26.3	30
0.55	12.4	16.5	20.6	24.8	28.9	33
0.6	13.5	18	22.5	27	31.5	36
0.65	14.6	19.5	24.4	29.3	34.1	39

Continuous intravenous infusion ^{(ref 4,5)} PERIPHERAL LINE (Critical Care, Outreach ONLY)

Initial rate: Septic shock
- 0.05 micrograms/kg/minute, titrated to target blood pressure
- See Table 3 below and also Guideline for the use of vasopressor agents by peripheral intravenous infusion, UHG
- Do not stop infusion suddenly as abrupt withdrawal can result in acute hypotension

Table 3: Peripheral line (restricted use - Critical care/Outreach ONLY) Indication: Septic shock Rate (mL/hour) for microgram/kg/min doses using 4mg/250mL infusion
Dose (microgram/kg/minute)	50kg patient	75kg patient	100kg patient
0.05microgram/kg/minute	9 mL/hr	14 mL/hr	19 mL/hr
0.1microgram/kg/minute	19 mL/hr	28 mL/hr	38 mL/hr
0.2microgram/kg/minute	38 mL/hr	56 mL/hr	75 mL/hr
0.3microgram/kg/minute	56 mL/hr	84 mL/hr	113 mL/hr
0.4microgram/kg/minute	75 mL/hr	113 mL/hr	150 mL/hr
0.5microgram/kg/minute	94 mL/hr	141 mL/hr	188 mL/hr
Doses rounded for convenience
Peripheral venous access ^{(ref 4)}: should ideally be of size 20G or more be sited proximal to the wrist in the arm avoid sites of flexion in awake patients avoid sites requiring more than one venepuncture there should be a return of blood following insertion and flush easily with 5-10mL of 0.9% sodium chloride

Monitoring

Monitor infusion site frequently - extravasation may cause local tissue necrosis
Monitor blood pressure continuously
Peripheral administration: a staff member competent in the administration of peripheral vasopressor MUST supervise the patient

Further information

Alternative concentrations
- For patients requiring high doses you may prepare a solution containing 8mg BASE (= 8mL of 1:1000 solution) in 50mL - unlicensed concentration ^{(ref 1)}
- Note: 8mg base in 50mL = 160 micrograms per mL
If CENTRAL line extravasation occurs, give phentolamine subcutaneously (into site of extravasation) 5 to 10mg in 10 to 20mL Sodium chloride 0.9% ^{(ref 2)}
If PERIPHERAL line extravasation occurs, see Guideline for the use of vasopressor agents by peripheral intravenous infusion, UHG
The product license for the solution for infusion stipulates "adults weighing over 50kg" .However, this monograph does not limit its use in patients below this weight^{(ref 3)}

Storage

Store below 25⁰C
Do not use if solution is brown, pink or dark yellow, or it contains precipitates

References

SPC Noradrenaline vials (Pfizer) June 2021

SPC: Noradrenaline pre-filled solution for infusion (Aguettant) March 2020

1: Injectable medicines guide- Medusa, downloaded 01/03/2022

2: UptoDate. downloaded 11/01/2024

3: Kidd, PS. "Noradrenaline 0.08mg/ml solution for infusion: patient's weighing less than 50kg". Personal opinion. September 2022

4. Intensive Care Society. Guidance for: The use of vasopressor agents by peripheral intravenous infusion in Adult Critical Care Patients. Version 1.1 November 2022 (interim update) . Available from: Intensive Care Society | Vasopressor Agents in Adult ICU (ics.ac.uk) Accessed: 11/01/2024

5: Guideline for the use of vasopressor agents by peripheral intravenous infusion, UHG, January 2024

Therapeutic classification

Vasoconstrictor sympathomimetic