Can adrenaline administration cause hypokalemia (low potassium levels) in patients?

Adrenaline-Induced Hypokalemia

Yes, adrenaline administration causes hypokalemia through beta-2 adrenergic receptor stimulation, which activates Na+/K+ ATPase and drives potassium into cells, resulting in a clinically significant drop in serum potassium levels.

Mechanism of Action

Adrenaline produces a biphasic effect on serum potassium 1:

• Initial hyperkalemia: Brief rise in potassium due to alpha-1 adrenergic receptor stimulation causing potassium release from hepatocytes 1
• Sustained hypokalemia: Prolonged decrease below baseline caused by beta-2 adrenergic receptor activation, which stimulates membrane-bound Na+/K+ ATPase in skeletal muscle cells, driving potassium intracellularly 2, 1

The hypokalemic effect is completely mediated by beta-2 receptors, as demonstrated when selective beta-2 antagonists (ICI 118551) completely blocked adrenaline-induced hypokalemia in controlled studies 2. During adrenaline infusion without beta-blockade, serum potassium fell from 4.08 to 3.32 mmol/L 2.

Clinical Significance and Magnitude

The potassium drop is substantial and clinically relevant:

• Adrenaline infusion at therapeutic doses causes serum potassium to decrease by approximately 0.75 mmol/L 2
• This decrease is accompanied by ECG changes, specifically T-wave flattening (mean -1.8 mm), which reversed when beta-2 blockade was administered 2
• The hypokalemia is transient but persistent during the period of elevated catecholamines 1

High-Risk Clinical Scenarios

Several situations dramatically increase the risk and severity of adrenaline-induced hypokalemia:

Patients on Thiazide Diuretics

• Prior thiazide treatment causes baseline hypokalemia (3.40 vs 3.83 mmol/L) 3
• During adrenaline infusion, potassium falls to significantly lower levels in thiazide-treated patients (2.73 vs 3.08 mmol/L) 3
• This represents profound hypokalemia that substantially increases ventricular arrhythmia risk 3

Combination with Theophylline

• Theophylline potentiates adrenaline-induced hypokalemia 4
• The combination can produce profound hypokalemia (<2.5 mmol/L) even with relatively low doses of both agents 4
• This combination also increases tachycardia beyond adrenaline alone 4

Critical Care Settings

• Cardiopulmonary resuscitation: Elevated endogenous catecholamines combined with therapeutic adrenaline may cause initial hyperkalemia, followed by significant hypokalemia after successful resuscitation 1
• Acute myocardial infarction: Catecholamine-induced potassium shifts are frequent and may contribute to arrhythmogenesis 1
• Multiple trauma and severe head injury: Low serum potassium levels are commonly observed due to elevated endogenous catecholamines 1

Prevention and Management

Beta-blockers prevent adrenaline-induced hypokalemia:

• Nonselective beta-blockers completely prevent the hypokalemic effect by blocking beta-2 receptors 5
• This mechanism may contribute to the cardioprotective action of beta-blockers by preventing arrhythmogenic hypokalemia 5

Monitoring recommendations:

• Regular potassium monitoring is essential during situations with elevated catecholamines (resuscitation, myocardial infarction, trauma, severe head injury) 1
• Resting serum potassium may underestimate risk in patients on diuretics, as transient profound hypokalemia during stress may not be captured 3
• Target potassium levels of 4.0-5.0 mEq/L to minimize arrhythmia risk, particularly in cardiac patients 6

Concurrent magnesium correction:

• Check and correct magnesium levels (target >0.6 mmol/L) before or during potassium replacement, as hypomagnesemia makes hypokalemia resistant to correction 6

Critical Caveats

• The hypokalemia represents intracellular shift, not total body depletion during acute catecholamine excess 1
• Potassium may rapidly shift back into extracellular space once catecholamine levels normalize 6
• Avoid aggressive potassium repletion during active high catecholamine states without careful monitoring, as rebound hyperkalemia can occur 6
• Patients with cardiac disease, heart failure, or on digoxin require particularly careful monitoring, as even mild hypokalemia increases arrhythmia and mortality risk 6, 7