How to measure norepinephrine (noradrenaline) and dopamine levels in patients?

Measuring Norepinephrine and Dopamine Levels

Measure norepinephrine and dopamine through plasma catecholamine assays using systemic venous blood samples, with strict attention to collection conditions including posture, temperature, medications, and stress levels, as these factors profoundly affect results. 1

Primary Measurement Method: Plasma Catecholamine Assays

Sample Collection Requirements

Critical pre-analytical factors must be controlled:

• Posture: Patient positioning significantly affects results; standardize whether supine or standing 1
• Rest period: Ensure adequate rest before collection to minimize stress-related elevation 1
• Temperature control: Ambient temperature influences catecholamine release 1
• Medication review: Many drugs interfere with catecholamine synthesis, metabolism, or sympathetic activity 1
• Dietary restrictions: Food intake affects measurements 1
• Stress minimization: Distress and anxiety cause acute elevations 1

Laboratory Analysis Techniques

High-performance liquid chromatography (HPLC) with electrochemical detection is the gold standard:

• HPLC provides sensitive, specific, and rapid quantification of norepinephrine, dopamine, and their metabolites 2, 3, 4
• Radioenzymatic methods using catechol-O-methyltransferase can measure catecholamines in samples as small as 0.1 mL 5
• Micellar liquid chromatography offers a simpler alternative requiring only dilution and filtration 3

What the Results Mean

Plasma norepinephrine reflects whole-body sympathetic nervous system activity when measured in systemic venous plasma, as it is released from sympathetic nerve endings with a small proportion entering circulation 1

Plasma dopamine has limited clinical utility as it has mixed neuronal and non-neuronal origins and is not specifically related to sympathetic neuropathy 1

Enhanced Measurement Approaches

Additional Metabolite Measurements

Measuring 3,4-dihydroxyphenylglycol (DHPG) alongside norepinephrine provides superior information:

• DHPG is the main neuronal metabolite of norepinephrine 1
• DHPG may be a more sensitive marker of overall sympathetic innervation than supine plasma norepinephrine alone 1
• Simultaneous measurement of norepinephrine and DHPG yields more information than either alone 1

Dynamic Testing

Orthostatic challenge testing enhances diagnostic value:

• Measure plasma norepinephrine both supine and after standing 1
• A subnormal orthostatic increment in plasma norepinephrine is a specific (though not sensitive) index of baroreflex-sympathoneural failure or sympathetic denervation 1
• Catecholamine responses to postural changes, exercise, or hypoglycemia can reveal autonomic dysfunction 1

Alternative Measurement Sites

Urine Collection

24-hour urine catecholamine measurements are available but less specific for acute sympathetic activity:

• Urine samples can be analyzed for norepinephrine, dopamine, and metabolites using HPLC or micellar liquid chromatography 2, 3
• Reference values for 24-hour urine: norepinephrine 169.8±58.25 nmol/24h, dopamine 757.2±382.6 nmol/24h 2
• Urinary measurements reflect integrated catecholamine production over time but lack temporal specificity 2, 3

Brain Tissue Assessment

For research purposes, homovanillic acid (HVA) in plasma or urine can estimate brain dopamine metabolism:

• HVA is the major metabolite of dopamine 6
• Peripheral contributions must be suppressed with debrisoquin to better reflect brain dopamine metabolism 6
• Measuring MHPG alongside HVA helps estimate residual noradrenergic contributions 6

Important Clinical Caveats

Plasma catecholamine levels respond slowly (over minutes) to physiological maneuvers, limiting their utility for rapid assessment 1

There is no neurochemical index that specifically assesses cardiac sympathetic innervation or function without invasive procedures like right heart catheterization and coronary sinus blood flow measurement 1

For routine clinical diagnosis, plasma catecholamine concentrations have limited usefulness compared to their value in experimental research settings 1

When to Measure

Plasma norepinephrine, epinephrine, and DHPG should be measured when assessing whole-body sympathetic activity alongside other physiological parameters including heart rate, blood pressure, cardiac output, and hormonal/metabolic events 1

In experimental conditions investigating autonomic function, plasma catecholamine measurements are mandatory, but standardization requirements make them impractical for routine clinical diagnosis 1