Propofol-induced inhibition of intestinal peristalsis involves enteric opioidergic pathways

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Introduction

In recent years, the short acting propofol is increasingly used for sedation in intensive care units (ICU) patients. Inhibition of intestinal peristalsis is a major problem in those critically ill patients and an inherent feature of sedatives such as barbiturates or midazolam. Since little is known about the action of propofol on intestinal peristalsis, this study investigates the effect of propofol on the ileal peristaltic reflex in vitro.

Methods

Ileal segments of adult guinea-pigs were mounted in silanized organ baths that contained oxygenated Tyrode solution (30 ml, 37°C). Prewarmed Tyrode solution was infused into the intestinal lumen, the infusion rate being 0.5 ml min^-1. The fluid passing the gut lumen was directed into a vertical outlet tubing which ended 4 cm (reflecting a pressure of 400 Pa) above the fluid level of the organ bath. This arrangement caused gradual filling of the intestine. When the intraluminal pressure reached a threshold an aborally moving wave of circular muscle contraction, measured as a spike-like increase in intraluminal pressure, propelled the intraluminal fluid to leave the system and thus caused emptying of the segment. The pressure threshold for eliciting peristaltic waves (peristaltic pressure threshold - PPT) was used to quantify the effects of drugs on peristaltic activity. Inhibition of peristalsis was reflected by an increase of PPT. After registration of normal peristalsis the segments were exposed to propofol (0.1–100 μM), which was administered cumulatively into the bath, i.e., to the serosal surface of at least 6 intestinal segments from 6 different guinea-pigs either alone, after application of vehicle (DMSO diluted with Tyrode solution), the GABA_A receptor antagonist bicuculline (BIC, 10 μM), or the opioid receptor antagonist naloxone (NAL, 0.5 μM).

Results

Propofol (0.1–100 μM) concentration-dependently increased the PPT, however, never caused complete inhibition of intestinal propulsion in the doses tested. While BIC (10 μM) failed to prevent the inhibitory effect of propofol, the increase in PPT was absent after pretreatment with NAL (0.5 μM).

Conclusions

Propofol inhibits intestinal peristalsis by increasing the PPT, but is less potent and effective compared to barbiturates or clonidine since it did not abolish peristaltic activity. The inhibitory effect of propofol seems not to be mediated through binding to GABA_A receptors, but seems to involve enteric opioidergic pathways.