Effect of intravenous diazepam on human lower oesophageal sphincter pressure under controlled double blind crossover conditions.

Abstract

SUMMARY The effect of diazepam on the lower oesophageal sphincter (LOS) pressure is controversial. Therefore, a double-blind crossover study was performed on 18 healthy volunteers to determine the sphincter response to intravenous diazepam-70, 140,280 ,ug/kg, which correspond to a total dose of 5, 10, and 20 mg, respectively. After the 5 and 10 mg dose no significant effect on LOS pressure could be observed when compared with placebo. After the 20 mg dose a significant rise in pressures (LJPLOS) was recorded for 40 minutes with a maximum JPLOS of + 16.2 + 6.6 (mean ± SEM) mmHg after 50 minutes (p < 0.01) (46 ± 1.3 % increase above the basal pressure). It is concluded that diazepam does not affect lower oesophageal sphincter competence and therefore does not increase the risk of regurgitation and pulmonary aspiration in premedicated patients.The high pressure zone between stomach and oesophagus, the functionally defined lower oesophageal sphincter, is a major determinant in the prevention of gastro-oesophageal reflux (Ingram et al., 1959;Pope, 1967;Winans and Harris, 1967;Cohen and Harris, 1970;Haddad, 1970;Cohen and Harris, 1971;Boesby, 1977;Fisher et al., 1977). Therefore, the effect of drugs which lower the sphincter pressure are of great clinical interest because of the increased risk of gastro-oesophageal reflux. Hall et al. (1975) Received for publication 25 July 1978 and our results based upon a pilot study, the present study was initiated to determine the effect of various doses of diazepam on lower oesophageal sphincter pressure in man in a controlled double-blind crossover study. MethodsThe original goal of the present study was to evaluate the effect of 70 and 140 ug/kg diazepam intravenously on lower oesophageal sphincter pressure in 12 subjects, a dose range corresponding to that administered by Hall et al. (1975). But, as no significant changes in lower oesophageal spincter pressures could be observed after these doses in a 50 minute period (group I), the studywas extended to six further subjects (group II) to investigate the effect of a higher dose (280 ug/kg) for a longer period of time (120 minutes). A dose of 140 ,ug/kg was given as a reference dosage. SUBJECTSEighteen healthy volunteers were studied in two groups. Group I consisted of 12 subjects, four of whom were females and eight males with a mean age of 23 years (range of 20 to 25 years). Group II consisted of six subjects (three females and three males) with a mean age of 24 years (range of 23 to 26 64 on 12 May 2018 by guest. Protected by copyright.

Domperidone-Induced Increase in Lower Oesophageal Sphincter Pressure Does Not Affect Azygos Blood Flow in Patients with Cirrhosis

“…lower oesophageal sphincter maintains a normal pressure and reacts normally to physiologic and pharmacologic stimuli in cirrhotic patients (3,4,13). This was reconfirmed in the preliminary part of this study: as is the case in normals (7,14), domperidone at a 10-mg dose caused a dramatic increase in sphincter pressure. Therefore, although lower oesophageal sphincter pressure was not measured in the study group of patients, there seems little doubt that this dose of domperidone increased lower oesophageal sphincter pressure in all these patients.…”

Endoscopically Assisted Water Perfusion Esophageal Manometry With Minimal Sedation

“…reported that midazolam did not change LES pressure or motility patterns, but Marsh et al reported that midazolam produced nonspecific esophageal motility changes (3, 4). Diazepam has been reported in three separate studies to increase, decrease, and not change LES pressure (5-7). Notably, Kwo et al .…”

“…Majority of studies demonstrated no difference in LES pressure or motility patterns, measured with and without sedation with benzodiazepines and local anesthetics (1-7). …”

Medical treatment of esophageal motility disorders

“…There is some evidence that sedatives have some positive influence on the symptoms in dysphagic patients which has been mainly ascribed to their central effects. Weihrauch et al [49] demonstrated in a double-blind, crossover study that diazepam (5 and 10 mg) had no significant influence on LESP, whereas 20 mg produced an increase of LESP [49]. However, in a recent study, diazepam (0.1 mg/kg intravenously) reduced LESP and increased the duration and amplitude of esophageal contractions [50].…”