Volatile anesthetics, including isoflurane, sevoflurane, and desflurane, are fundamental components of modern anesthesia practice. They are used for general anesthesia, during which the patient is unconscious and unaware of their surgery or procedure, and they are often combined with neuromuscular blocking agents that prevent movement. However, volatile anesthetics themselves also have some muscle relaxing effects that can assist with ensuring adequate ventilation and facilitating intubation. The mechanisms underlying these effects are complex and multifaceted, involving interactions with ion channels, neurotransmitter receptors, and intracellular signaling pathways.
One mechanism by which volatile anesthetics produce muscle relaxing effects is through their action at the neuromuscular junction, specifically by interacting with nicotinic acetylcholine receptors. These receptors are essential for mediating synaptic transmission that triggers muscle contraction. Volatile anesthetics enhance the efficacy of neuromuscular blocking agents by interacting synergistically at these receptor sites, reducing the efficacy of acetylcholine and prolonging blockade. This effect results from direct inhibition of receptor activation and stabilization of the inactive receptor conformation, thereby reducing the excitatory transmission required for muscle contraction (1). As a result, patients under volatile anesthetics require lower doses of neuromuscular blocking agents, improving safety margins during surgical procedures.
In addition, volatile anesthetics exert significant effects on smooth muscle tissues, particularly on uterine and vascular smooth muscle contractility. In a comparative study examining the effects of sevoflurane, desflurane, and isoflurane on isolated human uterine muscle, all three agents demonstrated a significant reduction in spontaneous contractility. This muscle relaxing effect of volatile anesthetics is thought to be mediated by the inhibition of calcium influx, a critical component of muscle contraction. In addition, volatile anesthetics may affect potassium channels, leading to membrane hyperpolarization and further reducing muscle excitability. These findings are clinically relevant in obstetric anesthesia, where uterine relaxation is sometimes desirable to prevent premature contractions or to facilitate surgical procedures such as cesarean sections (2).
Volatile anesthetics also have relaxing effects on vascular smooth muscle. Agents such as isoflurane and sevoflurane enhance acetylcholine-induced endothelium-dependent relaxation in vascular tissue. This process is thought to occur through nitric oxide-mediated pathways in which volatile anesthetics facilitate the release of endothelium-derived relaxing factors, resulting in vasodilation. This vascular smooth muscle relaxation is particularly beneficial in managing intraoperative blood pressure and ensuring adequate tissue perfusion. Furthermore, by enhancing acetylcholine-induced hyperpolarization, these anesthetics reduce intracellular calcium levels, thereby limiting vascular contraction (3).
The muscle relaxing properties of volatile anesthetics are also evident in their effects on the respiratory system, particularly airway smooth muscle. Isoflurane, for example, demonstrates significant broncho-relaxant properties, reducing airway resistance by inducing smooth muscle relaxation. This effect is mediated by inhibition of calcium ion influx and decreased intracellular calcium sensitivity, mechanisms that are essential for maintaining airway patency during anesthesia. Such effects are particularly beneficial during intubation and mechanical ventilation, as they reduce the work of breathing and facilitate gas exchange (4).
Last but not least, volatile anesthetics affect intracellular calcium sensitization mechanisms within smooth muscle tissue. Calcium sensitization involves the regulation of myosin light chain phosphorylation, a critical process for sustained muscle contraction. Volatile anesthetics have been shown to inhibit these pathways, resulting in reduced smooth muscle tone. This mechanism is particularly relevant in airway smooth muscle, where reduced calcium sensitivity leads to decreased muscle contraction and bronchodilation (5).
References
- Paul M, Fokt RM, Kindler CH, Dipp NC, Yost CS. Characterization of the interactions between volatile anesthetics and neuromuscular blockers at the muscle nicotinic acetylcholine receptor. Anesth Analg. 2002;95(2):. doi:10.1097/00000539-200208000-00022
- Yoo KY, Lee JC, Yoon MH, et al. The effects of volatile anesthetics on spontaneous contractility of isolated human pregnant uterine muscle: a comparison among sevoflurane, desflurane, isoflurane, and halothane. Anesth Analg. 2006;103(2):. doi:10.1213/01.ane.0000236785.17606.58
- Akata T, Nakashima M, Kodama K, Boyle WA 3rd, Takahashi S. Effects of volatile anesthetics on acetylcholine-induced relaxation in the rabbit mesenteric resistance artery. Anesthesiology. 1995;82(1):188-204. doi:10.1097/00000542-199501000-00024
- Cheng EY, Mazzeo AJ, Bosnjak ZJ, Coon RL, Kampine JP. Direct relaxant effects of intravenous anesthetics on airway smooth muscle. Anesth Analg. 1996;83(1):162-168. doi:10.1097/00000539-199607000-00028
- Kai T, Bremerich DH, Jones KA, Warner DO. Drug-specific effects of volatile anesthetics on Ca2+ sensitization in airway smooth muscle. Anesth Analg. 1998;87(2):425-429. doi:10.1097/00000539-199808000-00036