Chemotherapy is an essential tool for the treatment of cancer, but its interactions with other medications are an area of concern that requires careful consideration. Some research suggests that neuromuscular blocking agents, which are often used in anesthesia to induce muscle relaxation during surgery or mechanical ventilation, may experience interactions with chemotherapy. Understanding the potential mechanisms and ramifications of such interactions is necessary to guide treatment and further research.

Neuromuscular blocking agents include depolarizing and non-depolarizing agents. The most commonly used depolarizing agent is succinylcholine, which mimics acetylcholine and binds to nicotinic receptors at the neuromuscular junction to cause sustained depolarization, leading to muscle paralysis. Non-depolarizing agents, including drugs like rocuronium, vecuronium, and atracurium, compete with acetylcholine for binding at the nicotinic receptors, preventing depolarization and causing muscle relaxation ^1,2.

Chemotherapy drugs are known to cause neuromuscular dysfunction as a side effect. This can manifest as peripheral neuropathy, myopathy, or neuromuscular junction disorders. A recent review of 32 independent studies on chemotherapy-related movement dysfunction found that cancer survivors with chemotherapy-induced neurotoxicity had a range of challenges with both gross mobility (e.g., balance, walking, driving) and fine motor skills (e.g., tying shoes, writing, typing) ³.

Given these side effects, it is valuable to examine whether using chemotherapy and neuromuscular blocking agents in parallel may alter the expected effects of one or both. While data remain limited on this question, clinicians have identified a link between the use of chemotherapy agents and the incidence of myasthenia gravis.

Myasthenia gravis is a neuromuscular disorder leading to muscle weakness and fatigue. In a clinical case report, it was found very probable that at least one of the three chemotherapeutic agents used had a direct inhibitory effect on neuromuscular transmission, aggravating the patient’s pre-existing myasthenia gravis ⁴.

The exact mechanism for neuromuscular inhibition, while uncertain, was suggested to be due to disrupted calcium entry into the presynaptic nerve terminal, inhibiting presynaptic acetylcholine release. However, it could also have been a result of postsynaptic blockade, the drugs may have bound competitively to acetylcholine, or the drugs could have been interfering with muscle membrane conductance ⁴. If this is indeed the case, there may be a risk that the effects of neuromuscular blocking agents would be potentiated by chemotherapy, possibly impacting patient recovery and outcomes after anesthesia.

Any interaction between chemotherapy and neuromuscular blocking agents could have significant implications during surgery. Enhanced sensitivity to neuromuscular blocking agents can lead to prolonged paralysis, delayed recovery, and increased risk of postoperative complications such as respiratory failure ⁵.

A thorough preoperative assessment should be conducted to evaluate the extent of chemotherapy-induced neuromuscular dysfunction. The selection of neuromuscular blocking agents should consider the patient’s chemotherapy regimen—for instance, short-acting agents may be preferred to minimize the risk of prolonged paralysis. In addition, anesthesiologists may need to adjust the dose of neuromuscular blocking agents. During surgery, continuous neuromuscular monitoring is essential to guide the administration of neuromuscular blocking agents and ensure timely reversal. Postoperatively, close monitoring is crucial in order to detect and manage prolonged neuromuscular blockade ^1,2,5.

Descriptions of movement dysfunction linked to chemotherapy stem primarily from self-reported symptoms and functional limitations, with very few quantitative assessments of movement function ⁶. Advances in the objective characterization of patient symptoms and additional research on the underlying causes of chemotherapy-induced movement challenges is warranted in order to better understand and prevent any interactions between chemotherapy drugs and neuromuscular blocking agents.

References

1. Martin-Flores, M. & Sakai, D. M. Neuromuscular Blocking Agents. Pharmacol. Vet. Anesth. Analg. 202–214 (2024). doi:10.1002/9781118975169.ch16

2. Neuromuscular Blocking Agents – StatPearls – NCBI Bookshelf. Available at: https://www.ncbi.nlm.nih.gov/books/NBK537168/.

3. Wang, A. B. et al. A review of movement disorders in chemotherapy-induced neurotoxicity. Journal of NeuroEngineering and Rehabilitation (2021). doi:10.1186/s12984-021-00818-2

4. Ng, C. V. T. Myasthenia gravis and a rare complication of chemotherapy. Medical Journal of Australia (2005). doi:10.5694/j.1326-5377.2005.tb06612.x

5. Hunter, J. M. & Blobner, M. Under-dosing and over-dosing of neuromuscular blocking drugs and reversal agents: beware of the risks. British Journal of Anaesthesia (2024). doi:10.1016/j.bja.2023.12.001

6. Park, S. B. et al. Overview and critical revision of clinical assessment tools in chemotherapy-induced peripheral neurotoxicity. Journal of the Peripheral Nervous System (2019). doi:10.1111/jns.1233