Gastric residual volume in children: a study comparing efficiency of erythromycin and metoclopramide as prokinetic agents

T. F. Zatman, J. E. Hall and M. Harmer

Department of Anaesthesia and Intensive Care Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK*Corresponding author

Accepted for publication: February 1, 2001


    Abstract
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 Abstract
 Introduction
 Method and results
 Comment
 References
 
Metoclopramide may be used to stimulate gastric emptying when anaesthetizing children for emergency operations. Unfortunately, metoclopramide is associated with extrapyramidal side effects. Erythromycin, a motilin receptor agonist, is a prokinetic agent but its use has been little investigated in children. This randomized double-blind study compared the effects of premedication with oral metoclopramide 0.15 mg kg–1 or erythromycin 1 mg kg–1 on gastric emptying in 80 children undergoing tonsillectomy. Pre-operative fluids, premedication and anaesthetic technique were standardized and gastric volume was measured with an orogastric tube. Post-operative nausea and vomiting was recorded. Metoclopramide and erythromycin produced similar gastric volumes (0.29 and 0.24 ml kg–1) and there was no difference in post-operative vomiting. In the erythromycin group there were more patients with negative aspirates (45.9%) than in the metoclopramide group (35.1%), but the difference was not statistically significant. These results indicate that erythromycin may be as effective as metoclopramide as a prokinetic agent.

Br J Anaesth 2001; 86: 869–71

Keywords: anaesthesia, paediatric; metabolism, pre-operative fasting; lung, aspiration; gastrointestinal tract, fluid volume; premedication, metoclopramide; premedication, erythromycin


    Introduction
 Top
 Abstract
 Introduction
 Method and results
 Comment
 References
 
In emergencies, it may be necessary to anaesthetize children who are not fully starved and consequently at risk of pulmonary aspiration. Children are recognized to be at increased risk of aspiration compared with adults,1 2 and Coté and colleagues3 found that 76% of children had a gastric residual volume (GRV) of 0.4 ml kg–1 compared with 55% of adults.

Prokinetic agents such as metoclopramide can be used to reduce GRV. Metoclopramide is widely used as a prokinetic agent in adults and is licensed for premedication in children, but its use may be limited by its potential for producing extrapyramidal side effects. Erythromycin is an effective prokinetic agent in adults4 but there is no work examining its use for premedication in children. This study compared the effects of erythromycin and metoclopramide on GRV in children undergoing tonsillectomy. An active comparator was used in the study as the combination of temazepam, pre-operative fluid intake and a tonsillectomy operation was felt to be potentially emetogenic. Oral metoclopramide 0.15 mg kg–1 was chosen as it has been shown previously to be effective. This dose produces peak plasma concentrations in 1.5–2.5 h5 (the premedication interval used in our study), improves gastroesophageal reflux symptoms6 and reduces nausea and vomiting in children undergoing tonsillectomy.7


    Method and results
 Top
 Abstract
 Introduction
 Method and results
 Comment
 References
 
After Local Research Ethics Committee review and with written informed parental consent, 80 ASA grade I and II children of both sexes, aged 4–15 yr and undergoing tonsillectomy, were enrolled in the study. Exclusion criteria included a history of motion sickness, sleep apnoea, gastro-oesophageal reflux and other gastric pathology, and medication affecting gastric emptying.

The study was randomized and double-blind, and the children were allocated to two groups. Group 1 received oral metoclopramide 0.15 mg kg–1 and group 2 received oral erythromycin 1 mg kg–1 2 h pre-operatively. Children also received temazepam syrup 0.3 mg kg–1 and extremely weak lemon squash 3 ml kg–1 at this time. Children were allowed clear fluids up to the time of premedication.

A standard anaesthetic was given involving pre-oxygenation, induction with thiopentone 5–6 mg kg–1 and morphine 0.1 mg kg–1 and intubation after succinylcholine 1 mg kg–1. Anaesthesia was maintained with 1–2% halothane. Patients breathed spontaneously once the succinylcholine had worn off. After induction of anaesthesia, a blinded observer passed a multiport 16 g orogastric tube into the stomach. The tube position was checked by injecting 5 ml air down the tube and auscultating over the stomach. The orogastric tube was aspirated with a 20 ml syringe with the patient in supine, left and right lateral, Trendelenburg and reverse Trendelenburg positions. The tube was manipulated to various positions to ensure gastric emptying. The GRV was noted and the same volume of tap water returned to the stomach.

Nausea and vomiting was assessed for 18 h after operation using a numeric scale: 0=no nausea and vomiting; 1=nausea (assessed by asking children if they felt sick); 2=retching; 3=vomiting. Repeated incidents occurring within 15 min were classified as one episode. After operation, analgesia was provided by diclofenac (oral or rectal) or paracetamol. Pethidine was available.

Study size was determined using data from the work of Coté and colleagues.3 His first group consisted of in-patients anaesthetized for the first time: this group of 12 showed a mean GRV of 0.86 ml kg–1 and a standard error of 0.2. This gives a calculated standard deviation of 0.7 and, if a decrease to a GRV of 0.4 ml kg–1 were considered to be significant, 80 patients would be necessary to show significance at the 0.05 level for a study with a power of 0.85.

Six children were withdrawn from the study: two did not drink all of their prokinetic agent, three did not drink their pre-operative drink and in one case a blinded anaesthetist was not available to pass the orogastric tube. There were no differences between the two groups in age range (4–15 yr) and mean (SD) weight [36 (16) and 31 (16) kg]. Male:female ratio was 12:25 in both groups. GRV was the same in both groups (Table 1). An empty stomach occurred more frequently in the erythromycin-treated than in the metoclopramide-treated children, but the difference was not significant. The incidence of vomiting did not differ between groups (Table 1). Retching occurred in four children in the metoclopramide group and in one in the erythromycin group; all of these eventually vomited. Nausea occurred in five children in each group; all of these eventually vomited. No child received pethidine and none had extrapyramidal side effects.


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Table 1 Gastric residual volume and incidence of vomiting. Data are mean (SD), number (%) or median (interquartile range)
 

    Comment
 Top
 Abstract
 Introduction
 Method and results
 Comment
 References
 
There was no significant difference between the remaining GRV after pretreatment with erythromycin or metoclopramide. There was no difference in the incidence of post-operative nausea and vomiting in the two groups. Twenty per cent of the patients in each group had a gastric volume greater than 0.4 ml kg–1.

Erythromycin is a motilin receptor agonist. Erythro mycin 2 mg kg–1 has been shown previously to cause less gastrointestinal effects in adults than therapeutic doses,8 but in a pilot study in children9 a high level of post-operative nausea and vomiting occurred at this dose. We considered this dose to be too high for peri-operative use in a group of children already at risk of vomiting; consequently a dose of 1 mg kg–1 was used.

Only one previous study has compared the effects of erythromycin and metoclopramide on gastric emptying. This was a randomized crossover study in diabetic adults.10 Both drugs caused significant increases in gastric emptying, but it seemed more pronounced with erythromycin. The authors concluded that erythromycin could be used as an alternative to metoclopramide. The present study is the only work to date examining erythromycin as a pre-operative prokinetic agent in children, and it seems that the two treatments used in this study are similar in their effects on GRV. In emergencies, anaesthetists may wish to use erythromycin rather than metoclopramide, thus avoiding any potential for extrapyramidal side-effects. A dose of 1 mg kg–1 (lower than the therapeutic dose of 3–7 mg kg–1 in children over 2 yr) appears to avoid excessive gastrointestinal side-effects.


    References
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 Abstract
 Introduction
 Method and results
 Comment
 References
 
1 Kluger MT, Short TG. Aspiration during anaesthesia: a review of 133 cases from the Australian Anaesthetic Incident Monitoring Study (AIMS). Anaesthesia 1999; 54: 19–26[ISI][Medline]

2 Olsson GL, Hallen B, Hambraeus-Jonson K. Aspiration during anaesthesia: a computer-aided study of 185,358 anaesthetics. Acta Anaesthesiol Scand 1986; 30: 84–92[ISI][Medline]

3 Coté CJ, Goundsouzian NG, Liu LMP, Dedrick DF, Szfelbein S. Assessment of risk factors related to acid aspiration syndrome in paediatric patients—gastric pH and residual volume. Anesthesiology 1982; 56: 70–2[ISI][Medline]

4 Stern MA, Wolf DC. Erythromycin as a prokinetic agent: a prospective, randomized, controlled study of efficacy in naso-enteric tube placement. Am J Gastroenterol 1994; 89: 2011–13[ISI][Medline]

5 Kearns GL, Butler HL, Lane JK, Carchman SH, Wright GJ. Metoclopramide pharmacokinetics and pharmacodynamics in infants with gastroesophageal reflux. J Ped Gastroenterol Nutr 1988; 7: 823–9.[ISI][Medline]

6 Kearns GL, van den Anker JN, Reed MD, Blumer JL. Pharmacokinetics of metoclopramide in neonates. J Clin Pharmacol 1998; 38: 122–8.[Abstract/Free Full Text]

7 Ferrari LR, Donlon JV. Metoclopramide reduces the incidence of vomiting after tonsillectomy in children. Anesth Anal 1992; 75: 351–4.[Abstract]

8 Tack J, Janssens J, Vantrappen G, et al. Effect of erythromycin on gastric motility in controls and in diabetic gastroparesis. Gastroenterology 1992; 103: 72–9[ISI][Medline]

9 Hall JE, Harmer M. Erythromycin as a prokinetic agent in children. Anaesthesia 1996; 51: 503–4

10 Erbas T, Varoglu E, Erbas B, Tastekin G, Akalin S. Comparison of metoclopramide and erythromycin in the treatment of diabetic gastroparesis. Diabetes Care 1993; 16: 1511–4[Abstract]





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