Because of possible delayed gastric emptying, trauma patients undergoing emergency surgery may be at increased risk of pulmonary aspiration of gastric contents. One potential strategy to reduce this risk is to administer prokinetic drugs to accelerate gastric emptying, reduce the volume of stomach contents, and diminish the risk of regurgitation.
Erythromycin is a macrolide antibiotic that promotes gastric emptying in critically ill patients and those with gastroparesis related to diabetes mellitus.1,2 In cases of upper gastrointestinal bleeding, erythromycin is used clinically to improve endoscopic visualization of the stomach.3 We have previously reported that erythromycin significantly accelerated gastric emptying in stressed volunteers subjected to acute painful stimuli.4 However, few data have assessed its efficacy in patients undergoing emergency surgery and, consequently, there are no clear recommendations for its use in such patients.5 Because erythromycin is currently administered routinely before emergent general anesthesia in our unit, we studied the prokinetic effect of 3 mg•kg−1 erythromycin in nonfasted patients undergoing emergency trauma surgery by using ultrasound. Specifically, we examined the effect of erythromycin on the volume of gastric contents within a 90-minute period after administration.
This single-center prospective noninterventional case-series was approved by the IRB (Comité de Protection des Personnes Sud-Est IV, study identifier L14-171) and registered in the French (EudraCT number 2013-A01257-38) database for clinical trials. It was performed between September and November 2014 at the Édouard Herriot Hospital, Lyon, France. After providing written informed consent, patients scheduled for emergency trauma surgery were consecutively recruited and enrolled into the study. Patient inclusion criteria were ASA physical status I and II, age >18 years, and significant gastric contents (antral area >550 mm2 corresponding to a gastric volume between 70 and 150 mL)6,7 as assessed by ultrasound measurement at time T−30. Exclusion criteria were patient refusal, diabetes mellitus, history of gastroparesis, any contraindication to erythromycin therapy, and need for immediate emergency surgery resulting in insufficient time (120 minutes) to conduct the study.
An ultrasonographic measurement of the antral area was initially performed in the emergency department, before the patient was included in the study (time T−30). For each included patient, a second measurement of the antral area was performed 30 minutes later (time T0).
Immediately after this second measurement, erythromycin (3 mg•kg−1) diluted in 100 mL saline was administered IV over 10 minutes.
The gastric antral area was then measured serially at 30, 60, and 90 minutes after the start of the erythromycin infusion (times T30, T60, and T90). During the study period, no other medication was given. The patient entered the operating room after the last measurement of the antral area performed at time T90.
All measurements of the antral area were standardized and performed with the patient lying in a semiupright position by using ultrasonography (SonoSite, Inc., Bothell, WA, S-Nerve™, fitted with a 2–5.5-MHz probe) as previously described,6,8 with the abdominal aorta and the left lobe of the liver as internal landmarks.
Repeated measurements of the antral area allowed calculation of gastric emptying rates (GERs) before (T−30 to T0) and after (T0 to T90) erythromycin infusion and at the following time periods after administration: T0 to T30; T30 to T60; and T60 to T90, using the equation, GER = −[(AareaTn/AareaTn−30) − 1] × 100.9
The stomach was considered to be empty when the antral area was <340 mm2.6
A qualitative analysis of the antral content was performed during both the first (T−30) and the last (T90) measurements of the antral area. The antrum was defined as empty if it appeared flat, with juxtaposed walls, as containing clear liquid if it was distended with hypoechoic content, and as containing solid (or thick fluid) if it was distended with echoic content.10 If the antrum was distended with both hypoechoic and echoic content, it was judged to contain solid-liquid content. Whenever clear fluid gastric content was found, the grading scale (0, 1, and 2) previously described by Perlas et al.11 was also used.
Statistical analysis was performed using Statistica® version 6.0 (StatSoft, Tulsa, OK). The normality of the pairwise differences was assessed by using Shapiro-Wilk W test before performing paired t tests for comparisons of GERs during the study period (all P ≥ 0.11). The primary outcome of this study was the change in gastric emptying that occurred after erythromycin infusion (period T−30 to T0 versus period T0 to T90). To compare gastric motility before and after erythromycin administration, the GER was expressed as GER•min−1, obtained by dividing the GER value by 30 minutes for the GER before erythromycin administration (period T−30 to T0) and by 90 minutes for the GER after erythromycin administration (period T0 to T90). A paired t test was used to compare the GER•min−1 before versus after infusion of erythromycin. GERs were additionally compared between each 30-minute period (T−30 to T0, T0 to T30, T30 to T60, and T60 to T90). These comparisons were performed using paired t tests applying the Benjamini-Hochberg step-up procedure for multiple hypothesis testing correction.12 The corresponding adjusted 95% confidence intervals of the differences were also calculated, applying Bonferroni adjustment method.
Values in antral area during the study period were analyzed by using one-way analysis of variance. Qualitative data concerning both the antral content and the Perlas grading score between time T−30 and time T90 were analyzed by using χ2 test.
For each test, P <0.05 was considered statistically significant.
The primary outcome of the study was the assessment of the prokinetic effect of erythromycin. We hypothesized that the GER•min−1 would increase from 0.6%•min−1 (corresponding to delayed gastric emptying) to 0.8%•min−1 (corresponding to normal gastric emptying in healthy subjects), after erythromycin infusion, with an SD of 0.25%•min−1.9 According to these hypotheses, the power of the paired t test with 28 patients reached 85% with a significance level of 0.05.
Twenty-eight emergency trauma patients were analyzed (Table 1). Erythromycin was well tolerated by all patients. Particularly, no patient complained of nausea or stomach pain. Patient neither regurgitated nor aspirated gastric contents during the surgical procedure that followed the study period.
The GER•min−1 significantly increased after erythromycin administration: from −0.05 ± 0.26%•min−1 during the T−30 to T0 period to 0.17 ± 0.30%•min−1 during the T0 to T90 period (mean difference: 0.22 ± 0.44%•min−1, 95% confidence interval of the difference: 0.048–0.39%•min−1, P = 0.014). This increase was attributable to an increase in GER during the 30 minutes immediately after the start of erythromycin administration (T0 to T30) when compared with all other time periods (Fig. 1). We found no difference in the GER between the period preceding the erythromycin infusion (T−30 to T0) and the periods T30 to T60 (adjusted P = 0.71) and T60 to T90 (adjusted P = 0.43) (Fig. 1).
There were no statistically significant differences between the mean values of antral area measured at each time. An antral area <340 mm2 was not achieved in any patient at any time period (Fig. 2). The qualitative assessment of gastric contents was also not different between time T−30 and time T90 (Table 2).
Administration of erythromycin 3 mg•kg−1 was associated with more rapid gastric emptying in emergency nonfasting trauma patients. Although the difference was statistically significant, it did not reach GER•min−1 >0.8%•min−1, probably because gastric emptying was strongly delayed before erythromycin infusion in trauma patients. Moreover, this gastrokinetic effect of erythromycin was limited to the first 30 minutes after the start of the erythromycin infusion and did not change the antral area or the qualitative assessment of gastric contents.
Because we did not use a control group, we cannot fully assess the magnitude of the effect we observed. In addition, because we had no aspiration events, we cannot assess the clinical relevance of the increase in GER we observed. Nevertheless, erythromycin administration is relatively low cost and low risk, and the consequences of pulmonary aspiration can be severe. Further clinical trials are needed to determine the degree of clinical benefit from this strategy.
Name: Lionel Bouvet, MD, PhD.
Contribution: This author helped design the study, perform the data analysis, and write the manuscript.
Attestation: Lionel Bouvet approved the final manuscript, attests to the integrity of the original data and the analysis reported in this manuscript, and is the archival author.
Name: Emmanuel Boselli, MD, PhD.
Contribution: This author helped design the study, recruit and include the patients, and prepare the manuscript.
Attestation: Emmanuel Boselli approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.
Name: Eugénie Cheere, MSc.
Contribution: This author performed collection of the data.
Attestation: Eugénie Cheere approved the final manuscript and attests to the integrity of the original data.
Name: Adrienne Stewart, FRCA.
Contribution: This author helped write the manuscript.
Attestation: Adrienne Stewart approved the final manuscript.
Name: Bernard Allaouchiche, MD, PhD.
Contribution: This author helped for analysis and interpretation of data.
Attestation: Bernard Allaouchiche approved the final manuscript.
Name: Dominique Chassard, MD, PhD.
Contribution: This author helped for interpretation of data and helped write the manuscript.
Attestation: Dominique Chassard approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.
This manuscript was handled by: Avery Tung, MD.
The authors thank Dr. Fabien Subtil, MD, Department of Biostatistics, CNRS UMR 5558, Lyon, France, for his help in the preparation of the manuscript.
1. Reignier J, Bensaid S, Perrin-Gachadoat D, Burdin M, Boiteau R, Tenaillon A. Erythromycin and early enteral nutrition in mechanically ventilated patients. Crit Care Med. 2002;30:1237–41
2. Urbain JL, Vantrappen G, Janssens J, Van Cutsem E, Peeters T, De Roo M. Intravenous erythromycin dramatically accelerates gastric emptying in gastroparesis diabeticorum and normals and abolishes the emptying discrimination between solids and liquids. J Nucl Med. 1990;31:1490–3
3. Altraif I, Handoo FA, Aljumah A, Alalwan A, Dafalla M, Saeed AM, Alkhormi A, Albekairy AK, Tamim H. Effect of erythromycin before endoscopy in patients presenting with variceal bleeding: a prospective, randomized, double-blind, placebo-controlled trial. Gastrointest Endosc. 2011;73:245–50
4. Bouvet L, Duflo F, Bleyzac N, Mion F, Boselli E, Allaouchiche B, Chassard D. Erythromycin promotes gastric emptying during acute pain in volunteers. Anesth Analg. 2006;102:1803–8
5. Warner M, Caplan R, Epstein B, Gibbs C, Keelr C, Leak J, Maltby R, Nickinovich D, Scheiner M, Weinlander C. Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: application to healthy patients undergoing elective procedures: a report by the American Society of Anesthesiologist Task Force on Preoperative Fasting. Anesthesiology. 1999;90:896–905
6. Bouvet L, Mazoit JX, Chassard D, Allaouchiche B, Boselli E, Benhamou D. Clinical assessment of the ultrasonographic measurement of antral area for estimating preoperative gastric content and volume. Anesthesiology. 2011;114:1086–92
7. Perlas A, Chan VW, Lupu CM, Mitsakakis N, Hanbidge A. Ultrasound assessment of gastric content and volume. Anesthesiology. 2009;111:82–9
8. Bouvet L, Miquel A, Chassard D, Boselli E, Allaouchiche B, Benhamou D. Could a single standardized ultrasonographic measurement of antral area be of interest for assessing gastric contents? A preliminary report. Eur J Anaesthesiol. 2009;26:1015–9
9. Darwiche G, Almér LO, Björgell O, Cederholm C, Nilsson P. Measurement of gastric emptying by standardized real-time ultrasonography in healthy subjects and diabetic patients. J Ultrasound Med. 1999;18:673–82
10. Cubillos J, Tse C, Chan VW, Perlas A. Bedside ultrasound assessment of gastric content: an observational study. Can J Anaesth. 2012;59:416–23
11. Perlas A, Davis L, Khan M, Mitsakakis N, Chan VW. Gastric sonography in the fasted surgical patient: a prospective descriptive study. Anesth Analg. 2011;113:93–7
12. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol. 1995;57:289–300