What is the cause of muscle weakness and palpitations in a patient with Tumor Lysis Syndrome (TLS) after chemotherapy?

Hyperkalemia is the Cause

The answer is A. Hyperkalemia. The combination of muscle weakness and palpitations in a post-chemotherapy patient with tumor lysis syndrome (TLS) is the classic presentation of hyperkalemia, which results from massive release of intracellular potassium from rapidly lysed tumor cells 1, 2.

Why Hyperkalemia, Not Hypocalcemia

Hyperkalemia produces the exact symptom constellation described—cardiac manifestations (palpitations) and neuromuscular effects (muscle weakness)—due to elevated potassium levels in TLS patients 1. The American Society of Clinical Oncology emphasizes that this combination demands immediate assessment and treatment before progression to life-threatening arrhythmias or cardiac arrest 1, 2.

In contrast, hypocalcemia typically causes tetany and seizures rather than this symptom pattern, and asymptomatic hypocalcemia does not require treatment 1, 2. While hypocalcemia does occur in TLS as part of the metabolic derangements, it is not the primary cause of the presenting symptoms described 3, 4.

Pathophysiology and Timing

• TLS occurs when rapid tumor cell lysis releases massive amounts of intracellular potassium into the bloodstream, particularly relevant in the 12-72 hour window after chemotherapy initiation 1
• The hyperkalemia results from abrupt release of intracellular potassium from lysed cells, exacerbated by concurrent renal failure which impairs the kidney's ability to excrete the excess potassium load 1
• This metabolic derangement can overwhelm the body's normal homeostatic mechanisms 3

Clinical Significance and Mortality Risk

• Clinical TLS (which includes significant hyperkalemia) was associated with 83% mortality versus 24% in patients without clinical TLS 1
• Two of four deaths in a Burkitt's lymphoma cohort were directly attributable to hyperkalemia 1
• Hyperkalemia can progress to arrhythmias, ventricular tachycardia, and potentially cardiac arrest 2

Immediate Management Required

The American Society of Clinical Oncology recommends immediate ECG monitoring for cardiac arrhythmias in patients with hyperkalemia 1, 2. Treatment urgency depends on severity:

For Severe Hyperkalemia:

• Rapid insulin plus glucose to shift potassium intracellularly 1, 2
• Calcium carbonate to stabilize myocardial membranes 1, 2
• Sodium bicarbonate to correct acidosis 1, 2
• Emergency hemodialysis if persistent or life-threatening 1

For Mild Hyperkalemia:

• Aggressive hydration 1, 2
• Loop diuretics 1, 2
• Sodium polystyrene sulfonate 1, 2

Common Pitfall to Avoid

Do not delay treatment while waiting for laboratory confirmation if clinical suspicion is high—the combination of palpitations and muscle weakness in a post-chemotherapy TLS patient should trigger immediate intervention for presumed hyperkalemia, as progression to fatal arrhythmias can occur rapidly 1, 2.