Intravenous erythromycin overcomes small intestinal feedback on antral, pyloric, and duodenal motility

doi:10.1016/0016-5085(92)91103-B

Gastroenterology

Volume 103, Issue 1, July 1992, Pages 114-119

https://doi.org/10.1016/0016-5085(92)91103-B Get rights and content

Abstract

The retardation of gastric emptying caused by intraduodenal lipid is associated with suppression of antral contractions and stimulation of localized pyloric contractions. Similar patterns of motility have been described in patients with gastroparesis. The effect of erythromycin on the antropyloroduodenal motor responses to intraduodenal lipid was investigated. In 17 volunteers an intraduodenal lipid infusion (10% Intralipid) was given at 1 mL/min for 50 minutes. Either erythromycin (3 mg/kg) or saline was administered IV for 15 minutes, beginning 20 minutes after the start of the intraduodenal lipid infusion. Antral, pyloric, and duodenal motility were measured with a sleeve/sidehole manometric assembly. Intraduodenal lipid stimulated localized pyloric contractions. Erythromycin suppressed localized phasic (P < 0.003) and tonic (P < 0.002) pyloric pressure waves and stimulated antral (P < 0.003) and duodenal pressure waves (P < 0.02). After erythromycin antral pressure waves were usually of high amplitude (>50 mm Hg) and often associated with duodenal pressure waves. It was concluded that erythromycin overcomes the effects of intraduodenal lipid on antral, pyloric, and duodenal motility. These effects probably contribute to the gastrokinetic properties of erythromycin.

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Cited by (68)

High-Dose Oral Erythromycin Decreased the Incidence of Parenteral Nutrition-Associated Cholestasis in Preterm Infants
2007, Gastroenterology
Citation Excerpt :
Although the exact mechanism in which erythromycin facilitates advancement of enteral feeding is not fully understood, there is substantial evidence to suggest that the prokinetic action is mediated via the motilin pathway principally at the levels of the stomach and proximal small bowel.51–53 Stimulation of this pathway results in increase in the proximal gastric tone,54 greater amplitude and more frequent antral contractions,55–58 suppression of pyloric contractions and consequently reducing outlet resistance,52 and increase in the frequency of duodenal contractions.59 Recent studies have indicated the presence of 2 main types of motilin receptors.60
Background & Aims: Feeding intolerance because of functional gastrointestinal dysmotility and parenteral nutrition-associated cholestasis (PNAC) are common problems in preterm, very-low-birth-weight (VLBW) infants. This double-blind, randomized, placebo-controlled study aimed to assess the effectiveness of “high-dose” oral erythromycin as a prokinetic agent in decreasing the incidence of PNAC. Two secondary end points, including the time to achieve full enteral feeding and the duration of parenteral nutrition, were also evaluated. Methods: Infants consecutively admitted to the neonatal unit were randomized to receive erythromycin (12.5 mg/kg/dose every 6 hours for 14 days) or an equivalent volume of normal saline (placebo) if they attained less than half the total daily fluid intake (<75 mL/kg/day) as milk feeds on day 14 of life. Results: Of 182 VLBW infants enrolled, 91 received erythromycin. The incidence of PNAC was significantly lower in erythromycin-treated infants (18/91) compared with placebo infants (37/91; P = .003). Treated infants achieved full enteral nutrition significantly earlier (mean, 10.1; SE, 1.7 days; P < .001), and the duration of parenteral nutrition was also significantly decreased by 10 days (P < .001). Importantly, fewer infants receiving erythromycin had 2 or more episodes of septicemia (n = 4) compared with placebo patients (n = 13, P = .03). No serious adverse effect was associated with erythromycin treatment. Conclusions: High-dose oral erythromycin can be considered as a rescue measure for VLBW infants who fail to establish adequate enteral nutrition and in whom anatomically obstructive pathologies of the gastrointestinal tract have been excluded.
Mechanoreceptors of the Proximal Stomach: Role in Triggering Transient Lower Esophageal Sphincter Relaxation
2004, Gastroenterology
Citation Excerpt :
The intravenous dose of a 4.8-μg/kg bolus followed by infusion of 9.6 μg · kg−1 · h−120,21 was therefore chosen for the main study. An intravenous dose of 3 mg/kg has most frequently been used in studies of gastric motility and emptying26–29 because it generates powerful gastric contractions and is well tolerated.27,28,30,31 Furthermore, it induces a significant increase in tone of the proximal stomach during fasting,32 which has also been shown at 0.75 or 1.5 mg/kg.33,34
$Background & Aims$ : The role of fundic tension and stretch mechanoreceptors in triggering transient lower esophageal sphincter (LES) relaxation is still unknown. This information would be useful for the development of effective pharmacologic strategies. To elucidate this topic, gastric contractile activity was modified during isovolumetric gastric distention at 2 different volumes. $Methods$ : LES (Dentsleeve) and gastric (barostat) motility were recorded in 21 healthy subjects during studies comprising two 30-minute isovolumetric gastric distentions (placebo and glucagon or erythromycin). Glucagon (bolus of 4.8 μg/kg plus infusion of 9.6 μg · kg⁻¹ · h⁻¹) was administered at high intragastric volume (i.e., 75% of the threshold volume for discomfort; n = 7) and erythromycin (3 mg/kg) at high (n = 7) and low intragastric volume (i.e., at perception threshold; n = 7). $Results$ : Glucagon decreased (P < 0.05) baseline intragastric pressure and abolished gastric contractions (0 vs. 16.7 ± 2.3), whereas erythromycin increased (P < 0.05) baseline pressure and doubled (P < 0.05) the rate of gastric contractions at both volumes. Neither drug affected the rate of transient LES relaxations. Low intragastric volume induced a lower rate of transient LES relaxations (1.7 ± 0.3 vs. 5.7 ± 1.1; P < 0.01) and gastric contractions (11.8 ± 2.5 vs. 20.5 ± 3.1; P < 0.05) compared with high volume but similar baseline intragastric pressure (10.6 ± 0.6 vs. 11.9 ± 0.9 mm Hg). $Conclusions$ :Stretch receptors (gastric volume) seem to be more relevant than tension receptors in triggering transient LES relaxation.
Functional characteristics of the pylorus in patients undergoing pylorus-preserving gastrectomy for early gastric cancer
2002, Surgery
Citation Excerpt :
Serial changes in basal pyloric pressure, the rate of IPPWs, and the mean amplitude of IPPWs were analyzed in the period from T = −15 to T = 55. The erythromycin induced phase III-like activity in the pylorus was defined as “a period of regular contractions, which lasted at least 1 minute and showed a temporal overlap with the duodenal phase III-like activity after erythromycin administration.”6,21 Phase III-like activity in the duodenum was defined as “the occurrence of regular contractions at a frequency ≥ 10/minute for at least 2 minutes, and was followed by at least 5 minutes of relative quiescence (phase I).”6,20
Background. This study investigates the functional characteristics of the pylorus in patients undergoing pylorus-preserving gastrectomy (PPG) for early gastric cancer. Methods. In study 1, postprandial symptoms and gastric emptying were compared between 2 groups of 12 patients with early gastric cancer more than 1 year after either PPG (PPG group) or distal gastrectomy (DG) (DG group). Gastric emptying was evaluated with the dual isotope technique for liquids and solids separately. In study 2, pyloric motility was evaluated with a sleeve/sidehole manometric assembly in 7 patients undergoing PPG, which was compared with that in the preoperative patients. Results. In study 1, the overall modified Visick score of postprandial symptoms and the Sigstad dumping score were significantly lower in the PPG group compared with the DG group (P < .05). Early accelerated gastric emptying was observed in both groups for liquids, but only in the DG group for solids. In study 2, isolated pyloric pressure waves induced by intraduodenal lipid infusion and phase III-like activity induced by intravenous erythromycin infusion were preserved after PPG. Conclusions. The quantitative analysis of postoperative symptoms revealed that PPG patients were associated with better clinical conditions than DG patients. The clinical benefits of PPG are considered to be based on the function of the preserved pylorus. (Surgery 2002;131:613-24.)
GI complications in patients receiving mechanical ventilation
2001, Chest
Citation Excerpt :
Prokinetic agents, such as erythromycin, have been shown to promote gastric emptying in patients receiving MV and should be considered once mechanical obstruction is excluded. Erythromycin, 200 mg once daily, can improve gastric motility in these patients by increasing the amplitude of antral contractions and improving antroduodenal coordination.129,130,131 While erythromycin acts via motilin receptors, an intact vagal pathway has been shown to be necessary for its GI effects.132,133
Mechanical ventilation (MV) can be lifesaving by maintaining gas exchange until the underlying disorders are corrected, but it is associated with numerous organ-system complications, which can significantly affect the outcome of critically ill patients. Like other organ systems, GI complications may be directly attributable to MV, but most are a reflection of the severity of the underlying disease that required intensive care. The interactions of the underlying critical illness and MV with the GI tract are complex and can manifest in a variety of clinical pictures. Incorporated in this review are discussions of the most prevalent GI complications associated with MV, and current diagnosis and management of these problems.
Effects of low doses of erythromycin on the <sup>13</sup>C Spirulina platensis gastric emptying breath test and electrogastrogram: A controlled study in healthy volunteers
2001, American Journal of Gastroenterology
Citation Excerpt :
Erythromycin’s effect on gastric emptying is associated with a reduction in the lag phase and an acceleration of the postlag emptying rate of solids (13, 14). These effects have been attributed to an increase in antral contractility (15–17) and fundic tone (18), and an inhibition in pyloric contractility resulting in an improvement in antropyloroduodenal coordination (15, 16). The effects of erythromycin on gastric motility have been extensively studied in animals and man; however, only limited data exist on the dose-related effects of erythromycin on gastric motor function.
OBJECTIVE:
Electrogastrography and stable isotope gastric emptying breath tests (GEBTs) are relatively simple, noninvasive tests of gastric motor function that may be useful in monitoring the effects of therapeutic interventions. It was our primary objective to examine the effects of low dose i.v. erythromycin on the results of the ¹³C Spirulina platensis GEBT and electrogastrography. We were also interested in evaluating the reproducibility of these tests.
METHODS:
In 10 healthy subjects (five female, ages 23–37 yr), we simultaneously performed the GEBT, using a prepackaged meal (340 kcal), and electrogastrography on each of four different occasions separated by at least 1 wk. After performance of baseline studies, they were repeated in random order after the infusion of 50 mg of erythromycin (Er50), 100 mg erythromycin (Er100), and a placebo (saline). Breath samples were obtained at baseline and at 75, 90, and 180 min after the meal and T_1/2 and T_lag calculated. Electrogastrography recordings began 30 min before the test meal and continued for 2 h after the meal.
RESULTS:
Baseline and placebo T_1/2 and T_lag were similar. Er50 resulted in a modest acceleration of gastric emptying (T_1/2 Er50 vs baseline vs placebo = 104.0 vs 132.7 vs 125.5 min) and reduction in lag time (T_lag Er50 vs baseline vs placebo = 47.2 vs 61.5 vs 56.2 min). A similar decrease was seen in response to Er100. The baseline and placebo fasting and fed electrogastrography parameters were similar. After infusion of Er100, the percentage of normal slow waves in the first postprandial hour decreased relative to baseline and placebo (percent normogastria Er100 vs baseline vs placebo = 64.1 ± 7.5 vs 82.4 ± 6.4 vs 79.7 ± 5.5). This corresponded with an increase in percent tachygastria during the same period and an overall decrease in the mean dominant frequency. Similar but less striking changes were seen after administration of Er50. Replicate GEBTs showed a high degree of reproducibility both within and between individuals for T_1/2 and T_lag. In contrast, replicate electrogastrograms revealed moderate to high variability for all parameters except the dominant frequency.
CONCLUSION:
The stable isotope GEBT utilizing ¹³C S. platensis demonstrates responsiveness to the prokinetic effects of low dose i.v. erythromycin and good reproducibility.
AGA technical review on nausea and vomiting
2001, Gastroenterology
Citation Excerpt :
Although it has been recognized for some time that erythromycin, a macrolide, is associated with significant gastrointestinal effects, the possibility that these are related to the stimulation of motility was not recognized until recently. It is now clear that erythromycin exerts a dose-dependent stimulatory effect on foregut motility198 and inhibits isolated pyloric pressure waves and pyloric tone.199 These direct effects on contractile activity translate into acceleration of gastric emptying, abolition of the lag phase of solid emptying, emptying of nondigestible solids, and the induction of “dumping.”200-205

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Supported by a National Health and Medical Research Council Project Grant.

Part of this study was presented in abstract form at the American Gastroenterological Society meeting in 1991.

View full text

Intravenous erythromycin overcomes small intestinal feedback on antral, pyloric, and duodenal motility

Abstract

Lancet

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Improvement of gastric emptying in diabetic gastroparesis by erythromycin

N Engl J Med

Intravenous erythromycin dramatically accelerates gastric emptying in gastroparesis diabeticorum and normals and abolishes the emptying discrimination between solids and liquids

J Nucl Med

Erythromycin as prokinetic agent in postvagotomy gastroparesis

Dig Dis Sci

Erythromycin induces migrating motor complex in human gastrointestinal tract

Dig Dis Sci

Erythromycin accelerates gastric emptying by the induction of power contractions in the gastric antrum (Abstr)

J Gastrointest Motil

Motor mechanisms associated with slowing of the gastric emptying of a solid meal by an intraduodenal lipid infusion

J Gastroenterol Hepatol

Relationship of pyloric motility to transpyloric flow in healthy subjects (abstr)

Gastroenterology

Abnormal intestinal motility in diabetics with the gastroparesis syndrome

Eur J Clin Investigation

Antropyloroduodenal motor responses to intraduodenal lipid infusion in healthy volunteers

Am J Physiol

Topography and measurement of pyloric pressure waves and tone in humans

Am J Physiol