Shahbano Afzal, MD^*, Naseem Ali Sheikh, MBBS, FCPS, Waseem Ismat Chaudhry, MBBS, FCPS, Diplomat of The Board in Anaesthesia (I.R)^***, Zahid Iftikhar, MBBS, DA^****.

*FCPS Trainee (4th year), **Assistant Professor, ***Professor& Head, Dept of Anesthesiology, ****Anesthetist.

Dept of Anesthesiology Unit-II, Shaikh Zayed Hoapital, Lahore (Pakistan)

Correspondence: Dr. Shahbano Afzal, 433-F, Johar Town,, Lahore (Pakistan). Ph No: +92-42-5171029, Cell: +92-306-4466-718, E-mail: shahbano72@yahoo.com

ABSTRACT

Background: Prokinetic agents and H-2 receptor antagonists are commonly used to decrease the volume and increase the pH of the gastric fluid. This study was conducted to compare the effect of oral erythromycin–ranitidine combination and metoclopramide–ranitidine combination in reducing gastric fluid volume and acidity in patients undergoing elective surgery.

Methodology: 80 patients were divided into two groups by convenient sampling technique after meeting inclusion criteria; Group A was given oral erythromycin 250 mg-ranitidine 150 mg while group B was given oral metoclopramide 10 mg-ranitidine 150 mg two hours before surgery. Gastric fluid was aspirated with orogastric tube after induction. Volume and pH of the gastric fluid were determined.

Results: Data analysis of our study showed statistically significant reduction in mean gastric fluid aspirate volume in group A (3.4ml+2.3 vs. 7.2ml+3.1). (P-value = 0.001 and T-value = 6.24). There was no statistically significant difference between the two groups as far as increase in gastric pH was concerned (6.5+1.6 vs. 6.2+1.3). (T-value = 0.925 / Two tailed P-value = 0.36). In both the groups’ gastric pH was increased from the average normal value (0.3-2.9).

Conclusion: Combination of erythromycin-ranitidine is more effective than metoclopramide-ranitidine in reducing the gastric aspirate fluid volume and thus in prevention of acid aspiration syndrome.

Key words: Erythromycin, Ranitidine, Metoclopramide, Residual gastric fluid volume, Residual gastric fluid acidity.

Citation: Afzal S, Sheikh AN, Chaudary IW, Iftikhar Z. Comparative study of oral erythromycin-ranitidine combination and metoclopramide-ranitidine combination in reducing residual gastric fluid volume and acidity in elective surgery. Anaesth Pain & Intensive Care 2009;13(2);61-64

INTRODUCTION

Pulmonary aspiration of gastric contents has been one of the major causes of anesthesia-related deaths. Different methods have been advocated to reduce the volume and acidity of the residual gastric fluid, including: overnight fasting, use of prokinetic drugs, H-2 receptor antagonists, proton pump inhibitors and antacids¹. The prokinetics agents available include erythromycin²and metoclopramide³, and this property has led these to be used in patients with diabetic gastroparesis. Erythromycin⁴ in low doses reduces gastric fluid volume when given as a premedication drug prior to surgery. Studies show that metoclopramide alone or in combination with H-2 receptor antagonists causes reduction in gastric fluid volume and acidity⁵. But unfortunately it has extra pyramidal side effects. Ranitidineis H-2 receptor antagonist and increases the pH of gastric fluid. It is in use as chemoprophylaxis before induction of anesthesia to reduce the risk of acid aspiration syndrome.

In this study we aimed to compare the effect of oral erythromycin-ranitidine combination with metoclopramide-ranitidine combination in reducing residual gastric fluid volume and acidity in patients undergoing elective surgery.

METHODOLOGY

The study was conducted after the approval of ethical committee in the Department of Anaesthesia and Intensive Care Unit, Shaikh Zayed Hospital, Lahore. It was a quasi experimental study. A total of 80 patients, ASA I and II were enrolled from either sex, aged 20 – 50 years, scheduled to undergo elective surgery under general anesthesia. It was convenient sampling. Pregnant patients, those with history of gastrointestinal disease or extra pyramidal signs, patients taking H2 blockers, proton pump inhibitors, antacids or other drugs with known effects on gastric fluid volume and pH were excluded. Written informed consent was obtained from each patient during preoperative visit. Patients were selected on preoperative visit, no routine premedication was given and patients were asked to be nil by mouth at least six hours before surgery. On operation day, in the preoperative area patients were divided into two groups; Group A received combination I (tablet erythromycin 250 mg with tablet ranitidine 150 mg), while Group B patients received combination II (tablet metoclopramide 10 mg with tablet ranitidine 150 mg) with 10 ml of water two hours before surgery.

In the operating room, a standardized anesthesia technique was followed for each patient. ECG, heart rate and blood pressure was monitored. Induction of anesthesia was done by injection sodium thiopentone 5mg/kg, injection atracurium 0.6mg/kg. After intubation, anesthesia was maintained with isoflorane 0.5 – 1%, 40 % oxygen and 60% nitrous oxide. Then a multi-orificed orogastric tube (18 French) was passed and its correct location was confirmed by pushing air with 50 ml syringe and auscultation over the epigastrium. Before the commencement of the surgery, gastric fluid was aspirated and measured with a 50 ml syringe in the head down position. The pH of the aspirate, collected in a sterile bowl was measured with pH meter. Those patients with incomplete measurements were excluded from the study.

The data was entered and analyzed through statistical software SPSS version 10. Data analysis consisted of two steps. The mean fluid volume and mean pH with standard deviation was calculated for each combination of drug. Mean gastric fluid volume and pH were compared with each combination and statistical test ANOVA was applied. For comparison of proportions of categories of fluid volumes Chi–square test was applied.

RESULTS

80 patients were included in our study. They were divided in two groups i.e. 40 patients to each group. Group A was of Erythromycin–Ranitidine combination while group B was of Metoclopramide–Ranitidine combination. Data analysis of our study showed statistically significant reduction in gastric fluid aspirate volume in group A where mean volume was 3.4 ml as compared to group B where mean volume was 7.2 ml (P-value = 0.001 and T-value = 6.24). There was no statistically significant difference between the two groups as far as increase in gastric pH was concerned (T-value = 0.925 / Two tailed P-value = 0.36 which is greater than 0.05). In both the groups’ gastric pH was increased from the normal value (0.3-2.9). Analysis of the demographic profile (Mean age / Mean weight / Gender) showed no statistically significant difference.

Mean Gastric fluid aspirate volume

Data analysis of our study showed that mean gastric fluid volume was significantly reduced with erythromycin–ranitidine combination as compared to metoclopramide–ranitidine group. Mean aspirate volume with group A (erythromycin–ranitidine) was 3.4 ml (standard deviation = 2.3) as compared to group B (metoclopramide – ranitidine) where mean aspirate volume was 7.2ml (standard deviation = 3.1).This was shown to be statistically significant difference (p value less than 0.001 and t value 6.24). Qualitative analysis of the data also confirmed our observation. In group A (erythromycin–ranitidine) gastric fluid aspirate volume less than or equal to 10 ml was observed in 39 patients (97.5%) while only 1 patient had gastric fluid aspirate volume greater than 10ml (2.5%). While analyzing group B (metoclopramide–ranitidine) 34 patients (85%) had gastric fluid aspirate volume up to 10mls and 6 patients (15 %) had gastric fluid volume greater than 10 ml. Comparison of both groups again showed statistically significant difference (fisher exact one tailed P value was 0.05). Proportion of more than 10 ml gastric aspirate was significantly higher in group B as compared to group A.

Mean gastric pH

Our study showed that there was no significant difference in gastric pH between the two groups (t-value = 0.925 / two tailed P-value = 0.36 which is greater than 0.05). Mean gastric pH was 6.5 for group A (standard deviation = 1.6) while for group B mean gastric pH was 6.3 (standard deviation = 1.3). So no statistically significant difference in mean gastric PH was observed when comparing Erythromycin-ranitidine combination with Metoclopramide-Ranitidine combination as pre-anaesthetic medication to increase gastric pH.

Qualitative analysis of the data showed that in group A (erythromycin–ranitidine) pH of less than or equal to 5 was observed in 3 patients (7.5%) while the remaining 37 patients (92.5%) had pH greater than or equal to 5. Where as in group B (metoclopramide–ranitidine) 5 patients (10.0%) had pH less than or equal to 5 and 35 patients (90.0%) had pH greater than or equal to 5. Comparison of both the groups showed no statistically significant difference in high or low pH of gastric fluid aspirate (fisher exact one tailed P value was 0.356).

Comparison of mean ages

While considering the demographic profile, no statistically significant difference was observed while comparing the mean ages between the two groups (t-value = 0.285 / two tailed p-value = 0.776 which is greater than 0.05). Mean age in group A (erythromycin-ranitidine) was 30.8 years (standard deviation = 10.6) while in group B (metoclopramide-ranitidine) was 31.4 years (standard deviation = 9.6).

Gender status under study

Gender status of the patients under study also did not show any statistically significant difference (Chi-square value = 0.267 / Two tailed p-value = 0.606 which is greater than 0.05). In group A (erythromycin-ranitidine) 9 patients (22.55%) were females while 31 patients (77.5%) were males. In group B 11 patients (27.5%) were females while 29 patients (72.5%) were males.

Comparison of mean weights

Comparison of mean weight between the two groups did not reveal any statistical significant difference (t-value = 0.308 / two tailed p value = 0.551 which is greater than 0.05). Mean weight in group A was 63.9 kg (standard deviation = 11.4) while in group B was 62.3 Kg (standard deviation = 12.06).

Table 1: Comparison of mean gastric fluid volume and pH

	A	B	p-value
Mean Aspirate volume (ml) + SD	3.4+2.3	7.2+3.1	0.001
Mean gastric PH(ml) + SD	6.5+1.6	6.2+1.3	0.36

Table 2: Qualitative analysis of comparison of volume of gastric fluid aspirate

Groups Vol of gastric aspirates	A (Erythromycin -Ranitidine ) N (%)		B (Metoclopramide- Ranitidine) N (%)		Fishers Exact one tailed p value
Up to 10 ml	39 (97.5%)	34(85.0%)		0.05
More than 10 ml	1(2.5%)	6(15.0%)		0.05

Table 3: Qualitative analysis comparison of pH of gastric fluid aspirate

Groups pH range	A (Erythromycin -Ranitidine ) N(%)	B (Metoclopramide- Ranitidine) N(%)	Fishers Exact one tailed p-value
PH £ 5	3(7.5%)	5(10%)	0.356
PH > 5	37(92.5%)	35(90%)	0.356

DISCUSSION

The results of our study show that erythromycin-ranitidine group significantly decreased the volume of gastric fluid aspirate as compared to metoclopramide-ranitidine group. No significant difference in pH was noted between the two groups, yet it was significantly increased in both groups from the normal gastric pH (0.3-2.9)⁶. Hence combination of erythromycin-ranitidine was found to be more efficacious as it caused more decrease in the gastric residual fluid volume as compared to metoclopramide-ranitidine group.

The volume and acidity of the gastric contents are a result of gastric secretion, oral intake and gastric emptying. Traditionally a value of 2.5 for gastric pH and 25 ml (or0.4 ml/kg) for gastric fluid volume has been taken as a cut off value for development of aspiration syndrome^7-8. it has been reported from animal studies that a very low pH (less than 1), and breast milk or a dairy formula, predisposed to an increased severity of aspiration pneumonitis compared with less acidic content or a soya-based milk. More recently Soreide E et al⁹reported that for passive regurgitation and pulmonary aspiration to occur during anaesthesia more than 200 ml of gastric fluid volume is needed in adult patients, while in a healthy patient for elective surgery only 10-30 ml of gastric fluid are present. They also reported that in patients with gastro-oesophageal reflux or if vomiting occurs, even smaller gastric volumes may be pushed into the trachea. In both the groups that we studied the values were significantly lower than the values required for causing aspiration syndrome.

The prokinetic effects of erythromycin and metoclopramide is well established now^{10, 11}. Combination of erythromycin and metoclopramide therapy has been shown to be more effective than erythromycin alone in improving the delivery of nasogastric nutrition¹². Mclaren R et al¹³in their study showed that both erythromycin and metoclopramide can be used to facilitate gastric emptying and erythromycin seemed to be more effective than metoclopramide for enhancing gastric motility. Our results are consistent with the above mentioned studies confirming the effectiveness of erythromycin over metoclopramide when used as a prokinetic agent.

Although there was no statistically significant difference noted in both our study groups in mean pH value yet in both the groups the gastric pH was well above the cut off value of 2.5. A pH <2.5 was observed in 4 cases (3 belonged to erythromycin-ranitidine group while only 1 to metoclopramide-ranitidine group). Hong JY et al¹⁴ in their study evaluated the effect of IV metoclopramide and ranitidine on preoperative gastric contents in patients receiving IV anaesthesia for laproscopic gynaecologic surgery. They found mean gastric pH of 6.8 in patients given ranitidine thus concluding that ranitidine was useful in increasing pH of gastric contents. The literature thus supports our findings as mean gastric pH was increased in both our study groups and the quantitative increase was almost similar to the findings reported in the literature.

In our study blind aspiration through nasogastric tube was done to measure the volume of gastric content. Although this method is commonly employed, it results in incomplete emptying of the stomach and therefore underestimates gastric fluid volume. This may also explain why in our study we found mean gastric aspirate fluid volume to be much less than that reported in the literature (29+10 ml)9. Modern methods for measuring gastric emptying e.g. paracetamol absorption test, gastric emptying scintigraphy etc. can accurately quantify the prokinetic effect of these drugs.

CONCLUSION

We conclude that erythromycin-ranitidine combination is more effective than metoclopramide-ranitidine combination in reducing the gastric fluid volume. Both combinations significantly increase pH from the values quoted to cause acid aspiration injury.

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