Anesthetic Drugs Affecting Lower Esophageal Sphincter Tone

Introduction

• The LES is a specialized 3-4 cm thickened region of circular smooth muscle at the distal end of the esophagus that allows the passage of swallowed food and liquids to the stomach and prevents the reflux of gastric contents.¹
• In humans, the LES is asymmetric and does not form a complete ring. It is composed of semicircular clasp fibers adjacent to the lesser curvature of the stomach (incomplete ring in U shape) and oblique muscular fibers coming from the greater curvature of the stomach (sling fibers).¹
• The LES is innervated by both the parasympathetic and sympathetic systems. Sensory information is conveyed by both spinal and vagal sensory afferents. Sympathetic supply arises from T6-T10 and travels through the major splanchnic nerve.
• The LES has a basal tone of 15-30 mmHg above the intragastric pressure that is myogenic in origin. This basal tone of LES is modulated by enteric motor neurons, sympathetic and parasympathetic nervous systems, and several neurohumoral substances.¹
• Nitric oxide is the main inhibitory neurotransmitter involved in LES relaxation. Other inhibitory neurotransmitters on LES tones are adenosine triphosphate (ATP), vasoactive intestinal polypeptide (VIP), carbon monoxide, etc.¹
• Acetylcholine and tachykinins are involved in LES contraction.¹

Relevance of LES Tone

Gastroesophageal Reflux Disease (GERD)

• The pathophysiology of GERD can be multifactorial and can result from the presence of hiatal hernia, low esophageal sphincter, increased number of transient LES relaxations, increased abdominal esophageal pressure gradients (i.e., obese patients), and impaired esophageal motility.

Pregnancy

• In pregnant patients, the stomach and pylorus are moved cephalad by the gravid uterus. The intrathoracic displacement of the esophagus decreases the competence of the LES muscle. Higher progesterone and estrogen levels during pregnancy further decrease the LES tone. Gastrin, secreted by the placenta, decreases gastric pH. Additionally, gastric emptying is decreased with the onset of labor, pain, and the use of opioids. All these changes in combination put pregnant patients at risk for aspiration.

Anesthetic Drugs that Decrease LES Tone^2,3

• Atropine and glycopyrrolate decrease LES tone via their anticholinergic effects.
• Benzodiazepines (e.g., diazepam) decrease LES tone, although the mechanism is unknown.
• Opioids decrease LES tone via opioid receptors in the esophageal myenteric plexus.
• Volatile anesthetics also decrease LES tone.
• Sodium nitroprusside causes a dose-dependent decrease in LES tone.
• Nitroglycerines (e.g., isosorbide dinitrate, glyceryl nitrate) decrease LES tone.
• Beta-agonists (e.g., salbutamol, terbutaline) decrease LES tone.
• Propofol and dexmedetomidine do not decrease LES tone at the usual clinical doses. However, high doses are associated with a decrease in LES tone.

Anesthetic Drugs that Increase LES Tone²

• Metoclopramide increases LES tone as a dopamine receptor antagonist.
• Anticholinesterases (e.g., neostigmine, edrophonium) increase LES tone via acetylcholine.
• Succinylcholine increases LES tone and also increases gastric pressures during fasciculations. The increase in LES tone from succinylcholine may be from contractions of the diaphragmatic crura, cholinergic mimetic effect, or a reflex increase in gastric pressure.
• Nondepolarizing muscle relaxants have little effect or cause a modest increase in LES tone.
• Antacids increase LES tone by increasing gastric pH. Histamine-2 blockers and proton-pump inhibitors have no effect on LES tone.