Drugs that decrease Lower Esophageal Sphincter (LES) tone
- Nitroglycerins (Isosorbide dinitrate, glycerylnitrate, itramintosylate, trolnitrate)
- Anticholinergics (not when given with anticholinesterases)
- Beta-adrenergic agonists
- Aminophyllines (Theophyline, caffeine,cholintheophyline, glyphylin, oxitriphyline)
- Benzodiazepines (diazepam, flunitraqepam, nitrazepam, oxazepam, triazolam)
- Inhalational agents
- Tricyclic antidepressants
- Morphine (not when given with propofol)
- ?nitrous oxide
- Propofol (high doses only)
- Dexmedetomindine (high doses only)
- Residual neuromuscular blockade
- Calcium-channel blockers (Verapamil)
Drugs that increase LES tone
- Anticholinesterases (not when given with anticholinergics)
- Vecuronium (small increase)
- Alpha-aderenergic stimulants
- Histamie 2 blockers (H2B) (Cimetidine, Ranitidine)
- ? Nitrous oxide
- Propofol (normal doses)
- Dexmedetomindine (normal doses)
- Standard NMB reversal with Neostigmine AND Glycopyrollate
- Proton pump inhibitors (PPI)
Interestingly, the rates of aspiration were estimated at 14-26% in the days of ether, cyclopropane, and uncuffed ETTs. The LES is thought to be the major deterrent of regurgitation coupled with (to a much a lesser extent) the “flap valve” created by the angle of the esophagus and fundus (increases in this angle decrease regurgitation), as well as the “flutter valve” effect of the length of the flacid esophagus, and the “pinchcock” effect of the diaphragmatic cura. A hiatal hernia is associated with higher incidence of GERD but not always, the role of hiatal hernia for regurgiation is undefined.
The nervous supply of the LES is the parasympathetic vagus nerve; however, vagus nerve ligation is not associated with a change in resting sphincter tone. The sympathetic supply comes from T6-10, but the role of this is uncertain. Many receptors are present in the LES, including acetylocholine, noradrenaline, histamine, 5-hydroxytryptamine, prostaglandins, and the majority of the GI hormones.
There are no GABA or glycine receptors on the LES, however benzodiazepines decrease LES tone. Notably, propofol does not decrease tone except at high doses.
Narcotics generally decrease LES tone with a few exceptions. There are no opioid receptors on the LES; however, the esophageal mysenteric plexus has opioid receptors that are thought to play a role. Morphine is the prototypical opioid studied and lowers LES tone in all but one study. Nevertheless, it does not lower LES tone when patients are pretreated with propofol. The mechanism of this is unknown. According to Miller, morphine decreases the magnitude of LES-relaxation, as does metoclopramide.
Neuromuscular blockers (NMB) have varying effects. Succinycholine causes an increase in gastric tone with a higher degree of esophageal tone increase. The mechanism may be from contraction of the diaphragmatic crura or by a cholinergic mimetic effect or from a reflex from the increased gastric pressure. Nondepolarizing NMBs acutely (5-15 mins) have little effect or a modest increase in LES tone; however, residual blockade in the postoperative period increases the risk of aspiration/regurgitation.
Anticholinergics decrease LES tone and anticholinesterases increase LES tone. When given in combination for NMB reversal there is no net effect.
Inhalational agents all decrease LES tone in a dose-dependent manner. Nitrous oxide has been shown to minimally decrease LES tone in some studies but not others.
Antacids increase LES tone by increasing gastric pH. H2B and PPI’s do not change LES tone.
Beta-blockers show a mixed picture. Metoprolol increases LES tone while propranol exihibits no change.
Beta-adrenergic agonists seem to decrease LES tone.
Propofol and Dexmedetomidine do not lower LES tone at normal clinical doses. However, at high doses (2.4 ng/ml and 4 mcg/ml serum = BIS level <40) there is a decrease in LES tone.
B R Cotton, G Smith The lower oesophageal sphincter and anaesthesia. Br J Anaesth: 1984, 56(1);37-46 [PubMed:6140931]
Radu Tutuian, Clinical Lead Outpatient Services and Gastrointestinal Function Laboratory Adverse effects of drugs on the esophagus. Best Pract Res Clin Gastroenterol: 2010, 24(2);91-7 [PubMed:20227023]