Noradrenaline via Syringe Pump: Dilution, Infusion Rates and Titration in Practice

Noradrenaline as a vasopressor: mechanism of action

Noradrenaline (INN: norepinephrine) is a catecholamine with predominantly α-sympathomimetic activity. Clinically, vasoconstriction is the principal effect: systemic vascular resistance rises and, with it, mean arterial pressure. Noradrenaline is therefore used mainly for hypotension caused by vasodilatation. Typical situations are anaesthesia-induced hypotension and distributive shock.

Noradrenaline replaces neither fluid nor treatment of the underlying cause. It bridges the time until the cause of circulatory failure has been identified and treated. Vasopressor dosing does not follow a fixed regimen but is titrated to a defined target blood pressure.

Standard dilution for the noradrenaline syringe pump

Noradrenaline is supplied as a concentrate of 1 mg/ml in ampoules. For continuous administration, the compendium uses the following standard dilution (SmPC: Fachinformation Noradrenalin 1 mg/ml Konzentrat):

• 5 mg noradrenaline in 50 ml total volume
• gives 0.1 mg/ml = 100 µg/ml

In practice, 5 ml of the concentrate (1 mg/ml) is made up to a total volume of 50 ml. Suitable diluents and compatibilities should be taken from the current summary of product characteristics.

What matters most for safety is a uniform concentration within a department or emergency medical service area. At handovers between prehospital care, resuscitation room, operating theatre and intensive care unit, dosing errors often arise when different concentrations are continued at the same infusion rate. The syringe should therefore always be clearly labelled with drug, total amount, volume, concentration in µg/ml, time and initials.

Noradrenaline infusion rate by body weight

The following table applies only to a concentration of 0.1 mg/ml (100 µg/ml). It shows the infusion rate in ml/h for each dose in µg/kg/min (SmPC: Fachinformation Noradrenalin 1 mg/ml Konzentrat).

The table is a conversion aid. It is not a dose recommendation for the individual patient.

The calculation, step by step

For other body weights or intermediate steps, the infusion rate can be calculated using the general formula:

Infusion rate (ml/h) = dose (µg/kg/min) × BW (kg) × 60 ÷ concentration (µg/ml)

At 100 µg/ml this simplifies to: dose × BW × 0.6. Example from the table: 0.1 µg/kg/min × 70 kg × 0.6 = 4.2 ml/h.

Anyone using a different concentration must recalculate the infusion rates. The table above then no longer applies.

Initiation and titration

According to the summary of product characteristics, noradrenaline is titrated to a target blood pressure. As an example of a target, the compendium's fact base gives a MAP ≥ 65 mmHg. The individual target blood pressure depends on the clinical condition, comorbidities and organ perfusion and must be set by the treating physician.

A fixed starting dose is deliberately not given here. The starting dose should follow the current summary of product characteristics and the local SOP. The following principles apply to titration:

• Start low and adjust stepwise. After each change, wait for the effect and monitor blood pressure closely.
• Think in dose, not in ml/h. Documentation and handover in µg/kg/min (or in µg/min, if so defined locally) reduce misunderstandings.
• Review the target regularly. A rising requirement is a warning sign. It should prompt a search for causes such as hypovolaemia, haemorrhage, a cardiac cause, a septic focus or a malfunctioning pump.
• Adapt monitoring. Continuous haemodynamic monitoring is a prerequisite. For prolonged or higher-dose administration, invasive blood pressure monitoring is standard clinical practice.

Vascular access: CVC preferred, peripheral only short term

The summary of product characteristics specifies i.v. administration via syringe pump, preferably through a central venous catheter (CVC). The rationale is the risk of extravasation: noradrenaline leaking into the tissue can cause tissue necrosis through local vasoconstriction.

In the prehospital setting, in the resuscitation room or at induction of anaesthesia, a CVC is often not yet available. For this situation the compendium states:

• peripheral administration only short term
• via a large-bore, securely sited venous cannula
• inspect the insertion site regularly for swelling, pallor or pain
• plan central access early if it is foreseeable that the vasopressor will be needed for longer

The fact base contains no robust limits for a "safe" duration or dose of peripheral administration. Local standards and the current summary of product characteristics are authoritative here.

Syringe pump safety: the most common pitfalls

Alongside the calculation, infusion technique determines whether vasopressor delivery remains stable:

• Dedicated line: Noradrenaline runs through its own lumen. No boluses of other drugs are given through the same access. A bolus would flush through the vasopressor standing in the line and can cause an abrupt rise in blood pressure.
• No flushing of the noradrenaline line. For the same reason, the line should not be flushed. If it is occluded or disconnected, it is set up afresh.
• Syringe changes without interruption: Even brief pauses can cause hypotension in patients highly dependent on the vasopressor. Prepare in good time and change with overlap, in line with local nursing standards.
• Allow for start-up delay: At low infusion rates, the drug reaches the patient with a delay. Causes include dead space, system compliance and play in the syringe plunger. Before increasing the dose, check whether the pump is actually delivering.
• Plausibility check at handover: The concentration on the label, the programmed infusion rate and the documented dose must match.

Contraindication: fluid first

The summary of product characteristics lists hypovolaemia as the sole cause of hypotension as a contraindication. In this case: fluid first. In hypovolaemia due to haemorrhage or fluid loss, a vasopressor may raise the blood pressure reading in the short term. Organ perfusion does not improve as a result, and the actual problem is masked.

In practice, however, mixed pictures are common, for example a fluid deficit with additional vasodilatation. Fluid therapy and noradrenaline are then managed in parallel. The vasopressor bridges the time until the volume status has been optimised.

Combination with inotropes

Noradrenaline mainly increases vascular resistance. With impaired cardiac function, an inotrope may additionally be required. The ESC heart failure guideline recommends dobutamine for systolic blood pressure < 90 mmHg and hypoperfusion despite fluid optimisation. In marked hypotension, it should be combined with noradrenaline. The rationale is that dobutamine can lower blood pressure further via β2-mediated vasodilatation.

The compendium uses a separate standard dilution of 250 mg / 50 ml (5 mg/ml) for dobutamine. The infusion rates of the two catecholamines must therefore not be confused. Separate, clearly labelled syringes and lines are mandatory.

Quick check for the noradrenaline syringe pump

• Indication checked? Pure hypovolaemia excluded or fluid therapy started?
• Standard dilution 5 mg / 50 ml = 100 µg/ml correctly prepared and labelled?
• Target blood pressure set by the physician (e.g. MAP ≥ 65 mmHg)?
• Infusion rate checked against the table or formula (four-eyes principle)?
• Access: CVC preferred, peripheral only short term via a large-bore, secure cannula?
• Dedicated line, no boluses through the same line?
• Monitoring adequate, search for the cause initiated?

References

• Fachinformation Noradrenalin 1 mg/ml Konzentrat – aktuelle Fassung.
• McDonagh TA et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599–3726; 2023 Focused Update, Eur Heart J 2023;44:3627–3639.

This article does not replace clinical judgement in the individual case or the current summary of product characteristics and guidelines.