How to manage high noradrenaline levels?

Management of High Noradrenaline Levels

Alpha-adrenoceptor blockers are the first-line treatment for managing high noradrenaline levels, particularly in patients with norepinephrine-producing tumors or conditions causing elevated norepinephrine. 1

Diagnostic Considerations

Before initiating treatment, it's essential to determine the cause of elevated noradrenaline levels:

1. Potential causes:

   • Pheochromocytoma/paraganglioma (PPGL)
   • Essential hypertension (especially in younger patients) 2
   • Major affective disorders 3
   • Stress response in critical illness 1

2. Key diagnostic markers:

   • Elevated plasma and/or urine normetanephrine
   • Concurrent elevation of plasma/urine norepinephrine
   • Clinical symptoms: hypertension, tachycardia, palpitations, diaphoresis

Treatment Algorithm

For Norepinephrine-Producing Tumors (PPGL)

1. First-line pharmacotherapy:

   • Alpha-adrenoceptor blockers:
     • Selective α1-blockers: doxazosin, prazosin, terazosin
     • Non-selective α1 and α2-blocker: phenoxybenzamine
   • Start 7-14 days before any surgical intervention
   • Gradually increase dosage until blood pressure targets are achieved 1

2. Second-line/adjunctive therapy:

   • For tachycardia during α-blockade: Add β-adrenoceptor blocker (preferably β1-selective)
     • IMPORTANT: Never use β-blockers as monotherapy as this can precipitate hypertensive crisis 1
   • Metyrosine (inhibits catecholamine biosynthesis) as add-on where available
   • Calcium channel blockers for refractory hypertension or when α-blockers cause severe orthostatic hypotension 1

3. Perioperative management:

   • High-sodium diet and 1-2 liters of saline 24 hours before surgery
   • Compressive stockings to reduce orthostatic hypotension
   • Careful monitoring before, during, and after any procedure 1

For Critical Illness/Shock States

1. First-line vasopressor:

   • Norepinephrine is the first-choice vasopressor for shock 1
   • Target mean arterial pressure (MAP) of 65 mmHg 1

2. Second-line options:

   • Add vasopressin (up to 0.03 U/min) if target MAP cannot be achieved with norepinephrine alone 1
   • Epinephrine can be added or substituted when additional agent needed 1

3. For refractory shock:

   • Consider low-dose corticosteroid therapy for shock reversal
   • Hydrocortisone 200 mg per day as infusion or intermittent doses 1

For Essential Hypertension with High Noradrenaline

1. First-line therapy:

   • Alpha-adrenoceptor blockers
   • Beta-blockers (particularly in younger patients with elevated sympathetic tone) 2

2. Monitoring:

   • Regular blood pressure checks
   • Assessment of renal function (as renal noradrenaline spillover is 2.4 times normal in younger hypertensive patients) 2

Special Considerations

1. Dopamine-only producing tumors:

   • Alpha-adrenoceptor blockers are NOT recommended for exclusively dopamine-producing tumors 1
   • These patients are typically normotensive or hypotensive

2. Severity assessment in critical care:

   • Noradrenaline dose cutoffs to characterize cardiovascular failure:
     • Low dose: <0.2 μg/kg/min
     • Intermediate dose: 0.2-0.4 μg/kg/min
     • High dose: >0.4 μg/kg/min 4
   • Higher doses correlate with increased mortality

3. Cardiac protection in septic patients:

   • In selected septic patients with tachycardia (HR >120/min) receiving norepinephrine:
     • Consider esmolol (after adequate preload correction)
     • Exclusion criteria: severe LV dysfunction, AV block, norepinephrine >0.5 mg/kg/min 5

Potential Pitfalls and Caveats

1. Never use β-blockers as monotherapy in patients with norepinephrine-producing tumors, as this can precipitate hypertension by blocking vasodilatory β2-receptors while leaving α-receptors unopposed 1

2. Avoid medications that may trigger catecholamine crisis in patients with high noradrenaline who aren't receiving appropriate α-blockade 1

3. Monitor for orthostatic hypotension when using α-blockers, particularly with phenoxybenzamine which has longer-lasting effects

4. In liver disease patients requiring vasopressors for hepatorenal syndrome:

   • Terlipressin may be superior to norepinephrine in acute-on-chronic liver failure
   • Monitor for respiratory failure with terlipressin, especially in patients with other organ failures 1

5. In heart failure patients with sympathetic overactivation:

   • Beta-blockers (bisoprolol, sustained-release metoprolol succinate, carvedilol) can counteract deleterious effects of chronic sympathetic activation 1
   • Not all beta-blockers have equal efficacy in reducing mortality

By following this structured approach to managing high noradrenaline levels, clinicians can effectively address the underlying cause while minimizing risks of complications from sympathetic overactivation.