Year : 2007 | Volume
| Issue : 1 | Page : 7
"Effect of single oral dose of Sodium Rabeprazole administered a night before surgery on the intragastric pH and volume in adult patients undergoing elective surgery" a triple blind placebo controlled clinical trial
Altaf Hussain1, AbdulHamid Hasan Samarkandi2, Syed Shahid Habib3, Sayeed Nawaz1
1 Department of Anesthesiology, King Khalid University Hospital, Al-Riyadh, Saudi Arabia
2 Department of Anesthesiology and Surgical ICU, College of Medicine & King Saud University Hospitals. Al-Riyadh, Saudi Arabia
3 Department of Physiology, College of Medicine & King Saud University Hospitals, Al-Riyadh, Saudi Arabia
Department of Anesthesiology (41), Post Box No. 7805, King Khalid University Hospital, Al-Riyadh 11472
Source of Support: None, Conflict of Interest: None
|Date of Web Publication||5-Oct-2009|
| Abstract|| |
Back Ground: Saliva, duodenogastric refluxate and blood due to gastric mucosal entrapment can affect both pH and volume of gastric contents while sampling from stomach. This issue has never been exposed while evaluating the effectiveness of drugs used for the prophylaxis of acid aspiration. We considered all these factors.
Methods: This prospective, triple blind, randomized and placebo controlled clinical trial was conducted to explore the effect of single oral dose of Sodium Rabeprazole 20 mg on intragastric pH and volume in 100 adult inpatients of either sex, ASA I-III, and aged 15-70 years. The patients in Group S received (Sodium Rabeprazole 20 mg) while Group C received Placebo orally at 9.00 p.m., a night before elective surgery.
Gastric contents were aspirated with a large bore, multi-orifices gastric tube passed through an endotracheal tube placed blindly in esophagus after tracheal intubation and analyzed for the presence of bile salts, pH and volume.
Results: Fifteen cases (15.15%) were contaminated with duodenal contents and one with blood (1%). The proportion of the patients considered" at risk" according to the criteria defined (pH ≤ 2.5 and volume ≥ 25 ml) was statistical significant in Group S compared with Placebo (p value 0.0005).
Conclusion: Oral Sodium Rabeprazole 20 mg administered a night before elective surgery does improve the gastric environment at the time of induction of anesthesia, should the aspiration of gastric contents occur.
Keywords: Aspiration, duodenogastric refluxate, gastric pH& volume& Rabeprazole.
|How to cite this article:|
Hussain A, Samarkandi AH, Habib SS, Nawaz S. "Effect of single oral dose of Sodium Rabeprazole administered a night before surgery on the intragastric pH and volume in adult patients undergoing elective surgery" a triple blind placebo controlled clinical trial. Saudi J Anaesth 2007;1:7
|How to cite this URL:|
Hussain A, Samarkandi AH, Habib SS, Nawaz S. "Effect of single oral dose of Sodium Rabeprazole administered a night before surgery on the intragastric pH and volume in adult patients undergoing elective surgery" a triple blind placebo controlled clinical trial. Saudi J Anaesth [serial online] 2007 [cited 2020 May 27];1:7. Available from: http://www.saudija.org/text.asp?2007/1/1/7/56265
Pulmonary aspiration of gastric contents is the inhalation of gastric contents into the larynx and lower respiratory tract. Its severity depends upon the nature (pH) and amount (volume) of the aspirated material, and the host's factors that predispose the patient to aspirate and to modify the response  . General anesthesia itself is a major risk factor that predisposes the patient to aspirate due to the loss of protective airway reflexes. The principle of protecting the airways prophylactically by pharmacological method forms one of the cornerstones of the practice of anesthesiology.
Saliva, duodenogastric refluxate and blood due to gastric mucosal entrapment are the factors that can affect both pH and volume of gastric contents and has never been considered significant while sampling from stomach in any previous study conducted for the effectiveness of the drugs used for the prophylaxis of acid aspiration. Our aim was to study the effect of single oral dose as used in the short term management of acid related disorders of upper gastrointestinal tract  of sodium rabeprazole on intragastric pH and volume by excluding those cases contaminated with above mentioned factors.
| Patients and Methods|| |
The study project proposal No.05-501 was approved by the College of Medicine Research Center (CMRC) as well as College Ethics Committee. Informed consent was taken from all patients.
Patients and Group Assignment
We examined the effect of single oral dose of Sodium Rabeprazole 20 mg administered at 9.00 p.m., a night before elective surgery on intragastric pH and volume in adult inpatients aged 15-70 years to be intubated with cuffed endotracheal tube, of American Society of Anesthesiologists (ASA) physical status I-III, and Mallampati class I-III.
Patients with upper gastrointestinal disorders, Body Mass Index (BMI) more than 40 kg/m 2 , receiving medications known to affect the secretory and /or motor functions of the stomach, Mallampati class V, intestinal obstruction, Diabetes Mellitus with autonomic neuropathies, parturients and the patients who were premedicated but could not be operated due to cancellation of surgery, were also excluded from the study.
We repacked the drugs to be studied in envelopes of the same size, shape and color and their names were changed as drug one, drug two, drug three…etc. by a person who was not taking part in the study to keep the patients and investigators blinded of it. The group assignment paper was sealed in another envelope that was opened after the statistical analysis. Statistician was also blinded of group assignment (triple blind). We made two equal groups of these envelopes, one for males and the other for females for equal distribution. On the pre-operative anesthesia visit, a day before surgery, the purpose of study was explained to each patient. We asked each patient to pick up only one envelope from the envelopes (randomization). Thus, the patients were allocated either to Group C (control) or Group S (Sodium Rabeprazole) randomly by sealed envelope method. Age, sex, weight, height, (BMI), ASA physical status, Mallampati Class and the drug given were recorded for each patient. The drugs to be studied were given orally with 20 ml of drinking water at 9.00 p.m., a night before elective surgery. The patients also received oral diazepam 10 mg at the same time. According to the Hospital policy, all patients were fasted from 12midnight. Upon arrival in the waiting area of the operating room, all patients were asked if they had been aware of any unusual feelings (side effects) after taking the study drug, a night before surgery. It was also recorded.
Collection and Analysis of Gastric Contents
In the operating room, routine monitors were attached to the patients and turned on. After pre-oxygenation with 100 % O 2 by face mask using four breath vital capacity method, anesthesia was induced with injection fentanyl 1-2 ΅g/kg, propofol 2-3 mg/kg and rocuronium 0.6-0.9 mg/kg. The lungs were ventilated taking care not to inflate the stomach. Maintaining cricoid pressure, trachea was intubated with cuffed endotracheal tube. Placement and position of endotracheal tube was confirmed with EtCO 2 monitor and then secured properly. After establishing stable anesthesia, an endotracheal tube sized 8.5 mm internal diameter coated with paraffin liquid internally and well lubricated with water soluble jelly externally was passed via oral route into the esophagus with anterior displacement of larynx. A predetermined length (Xiphoid-ear lobules-nasal tip) of stomach tube (Jamjoom Medical Industries, Jeddah, Saudi Arabia) sized 18 F was passed through this esophageally placed endotracheal tube to prevent entry of saliva through its side holes into its lumen. Placement of this tube within the stomach was verified by auscultation over the epigastrium during insufflation of 10-15 ml of air. Gastric contents were gently aspirated manually with 60 ml of syringe by an investigator who was blinded of the group assignment. Applying manual pressure over the epigastrium while the patient was in supine and then left and right lateral positions, gastric tube was then manipulated to ensure maximum emptying of gastric contents. The stomach tube was removed followed by esophageally placed endotracheal tube. Any problem encountered during inserting or removing the oro-esophageally placed endotracheal tube or gastric tube was also recorded. The volume of gastric contents was measured with graduated syringe and pH with pH meter (Model 215 version 3.4, Denver Instrument Company, United States). The pH meter was calibrated using standard buffers at pH values of 4, 7 and 9.20. This pH meter has a precision of 0.01 units over the entire pH range. A minimum of one-milliliter volume of gastric contents was sufficient for pH determination with pH meter. However, samples less than one-milliliter were tested with wide range (0-14) pH paper (Universal indicator pH papers, MERCK, Germany). In case of little quantity of gastric contents, we cut the gastric tube at multiple sites and aspirated material with disposable plastic pipette. Samples less than 0.5 ml were considered as no gastric contents because a minimum volume of 0.5 ml of gastric contents was sufficient to wet the pH paper. Using bile salts as a marker for bile we applied Hay's Sulphur test for the presence of bile salts.
In this test finely powered Sulphur is sprinkled upon the surface of cool (17 0C or below) liquid.
A-If Sulphur sinks down at once, bile salts are present in the amount of about 0.01% (100μg/ml)  .
B-If Sulphur sinks only after agitation, bile salts are present in the amount of 0.0025% (25 ΅g /ml) or more  .
C- If Sulphur remains floating upon the surface of liquid, the bile salts are absent.
Anaesthesia was maintained with Air, O 2 and sevoflorane. The patients also received incremental doses of fentanyl and rocuronium as required. At the end of surgery, injection atropine and neostigmine were given to antagonize the residual effect of rocuronium. All patients were extubated in lateral position and then transferred to recovery room.
Time since premedication, time since Nothing Per Orem (NPO), pH, volume of gastric contents and result of Hay's Sulphur test were also recorded for each patient.
Statistical tests were performed using GraphPad Software, Inc., San Diego, United States, and results are expressed as absolute values (percentage) or mean ± SD. Statistical comparisons between the two groups were carried out using Student's (unpaired) t test for age, weight, height, BMI, time since premedication, time since NPO, pH and volume. Fisher's exact test was applied for sex and risk of aspiration according to the criteria defined (pH ≤ 2.5 and volume ≥0.4 ml/kg or 25 ml). A p value of less than 0.05 was considered statistically significant.
Power analysis revealed that the sample size (n=30 in each group) of the study was sufficient to detect a difference of 0.7 between groups in gastric pH and volume at a significance level of 0.05 (= α) with a power of 0.85  .
| Results|| |
One hundred (100) adult inpatients undergoing elective General (n=52), Orthopedic (n=21), Gynecological (n=15), Urology (n=6), Thoracic (n=5) and Plastic (n=1) Surgery were studied. Physical characteristics of patients and timings of events are shown in [Table 1]. There was no statistically significant difference between the two Groups.
We obtained gastric contents of all the patients. Hay's Sulphur test was performed on 99 samples and was positive in 15 patients (15.15%) while one sample was contaminated with blood (1%). The pH of all the samples was checked with pH meter. The average (range) pH and volume of cases contaminated either with duodenal contents or blood was 5.47 (2.75-7.51) and 15.53 (3.0-32.0) ml& 6.52 and 3.0 ml, respectively. These contaminated cases were not included in the statistically analysis while analyzing pH, volume and proportion of patients at risk.
The pH and volume of gastric contents are shown in [Table 2]. There was a statistically significant difference between the two Groups regarding pH (p <0.0001) and volume (p 0.0005) of gastric contents.
The proportion of the patients considered" at risk" of significant lung injury should aspiration occur is shown in the [Table 3]. There was a statistically significant difference between the two Groups (p value 0.0005).
One patient complained of headache in Group S while one patient in Group C had severe bronchospasm at induction. No problem encountered during aspiration of gastric contents with oro-esophageally placed endotracheal tube. All patients were discharged from the hospital without any problem.
CONCLUSION: Oral Sodium Rabeprazole 20 mg administered a night before elective surgery does improve the gastric environment at the time of induction of anesthesia, should the aspiration of gastric contents occur.
| Discussion|| |
Aspiration of gastric contents (Mendelson's syndrome) was first described by Mendelson CL in 1946 in obstetrical cases  . Since then a lot of work has been done and published in the form of brief reports, forums, original papers, editorials and review articles in anesthesia literature.
There are three potential sources of contamination of gastric contents while taking sample from the stomach. These are salivary secretions, duodenogastric reflux and gastric mucosal entrapment. In all the previous studies conducted, this issue has never been addressed. All the three above mentioned factors affect both the pH and volume of gastric contents.
Let us see, one by one, how these factors affect pH and volume?
In the awake state, the basal rate of saliva production is about 0.5 ml/minute, but this may increase to 5ml /minute with intense stimulation  . Firstly, insertion of oropharyngeal airway, act of laryngoscopy and tracheal tube insertion are the stimulants that increase the production rate of saliva. Secondly, saliva pools due to the lack of swallowing reflex in the oropharynx and hypopharynx, the dependent parts of neutral supine position. Thirdly, in an intubated patient, the esophagus may be occluded by inflated endotracheal tube cuff and can interfere with stomach tube insertion. It is difficult to pass stomach tube without the entry of saliva through the side holes into the tube because the stomach tubes do not have obturator as we use in tracheotomy tubes. To overcome this problem we passed stomach tube through an endotracheal tube placed blindly into the esophagus after tracheal intubation. This technique also avoids finding the upper esophageal opening and coiling of the tube in the mouth even after successfully passing the distal end of tube into stomach. The fringe benefit that we got with this technique was the manipulation of gastric tube with ease. It is very interesting that gentle suction with the syringe is required while removing the gastric tube after aspiration; other wise, gastric contents will fall down at the level of distal end. Without endotracheal tube placed in esophagus, we can aspirate saliva. Although, this technique of passing stomach tube is old  , but no body has utilized it for sampling gastric contents in any previous study.
Duodenogastric reflux, the trans-pyloric retrograde flow of duodenal contents into the stomach, is well known, well established clinical entity ,,,, with variable incidence. Mild to moderate duodenogastric reflux occurs in approximately one third of normal subjects, and in one third of patients with non-ulcer dyspepsia as shown by the radiological tests of Keet  and Huges et al  , in other words, the pylorus is normally not competent in a significant percentage of normal subjects and approximately the same percentage of patients with non-ulcer dyspepsia. In healthy subjects, duodenogastric reflux occurs sporadically in the interdigestive state and is a normal phenomenon in the postprandial period and its underlying mechanisms are poorly understood  .
Duodenal contents consist of bile, pancreatic juice, small intestine secretion and Brunner's gland secretion. All these secretions are alkaline in nature due to HCO 3 - ions  . When duodenal contents flow in retrograde fashion, then mix with acid in the stomach and bring the pH towards less acidity thus affecting pH and at the same time increase the volume of gastric contents similar to oral ingestion of sodium citrate. To overcome this problem, firstly, we aspirated gastric contents in optimal position of the patient as described by Niinai et al  . Secondly, we passed a predetermined length of stomach tube  so that it should not go beyond pyloric sphincter. Thirdly, we excluded those samples that were positive for Hay's Sulphur test while analyzing pH and volume of gastric contents. Lastly, the mean (average) volume of contaminated cases with duodenal contents was 15.53 (3.0-32.0) ml that can only be aspirated from storage organ like stomach. Duodenum can be full of secretions, when there is intestinal obstruction but we did not include such cases in our study.
Finally, gastric mucosal entrapment occurs particularly when air and fluid has been aspirated and stomach is collapsed. Bleeding may occur and can be seen in stomach tube. It is commonly believed that the sump tubes (double-lumen) are more effective than the single lumen variety, but there is no scientific evidence to support this view  However, any sample containing any amount of visible blood mixed with gastric contents was not considered for pH and volume analysis.
The Bilitec TM 2000 ambulatory bile reflux recorder is currently the only commercially available device that is proven effective in measuring bile reflux  . Using Bilirubin as a marker for bile, the Bilitec 2000 recorder captures the frequency and duration of bile exposure in either the stomach or the esophagus over a 24-hour period. This method was not feasible for us, we applied Hay's Sulphur test to detect bile salts in the gastric contents. This simple, sensitive and fairly reliable test  depends on the principal that bile salts have the property of reducing the surface tension of fluids in which they are contained  , was devised in1886 by Matthew Hay (1855-1932) Professor of Forensic Medicine at Aberdeen University.
One of our patients had severe bronchospasm at intubation. Fiberoptic bronchoscopy did not support the evidence of aspiration of gastric contents. This patient was scheduled for thoracoscopic sympethectomy. A chest tube was inserted at the end of procedure and the patient was extubated and observed over night in surgical ICU. Follow up spiral CT chest showed bronchioectatic changes in the right middle lobe, the possible cause of bronchospasm. Headache, nausea and vomiting are common side effects of rabeprazole.
The drawbacks of the current project include
a- The use of ASAI-III patients and .We should have included ASA IV-V patients as well. Thus, the clinical relevance of the study may be weak.
b-The common techniques to aspirate the residual volume of gastric contents are Fiberoptic gastroscopy, Indicator dilution technique and Blind aspiration via gastric tube
In this current study total gastric volume may have been underestimated by the blind aspiration via gastric tube in each patient due to the functional divisions of the stomach into antral and fundal sacs. A similar error would occur in all patients of both groups and inter-group comparisons are, therefore, valid. This method is simple, inexpensive, and easy to perform and has been widely used in the similar studies. As the effect of a drug on intragastric volume reduction is difficult to demonstrate using blind aspiration via gastric tube, the pH values seem preferable, therefore, for comparisons of results in the literature. Moreover, pH is more important than the volume as a risk factor for the severity of aspiration pneumonitis  .
| Acknowledgements|| |
This was a self-sponsored project afforded by the principal investigator. Authors are very thankful to the laboratory staff of Clinical Chemistry Department, Nursing Department and colleagues of Anaesthesia and Surgical Departments of King Khalid University Hospital for their co-operation.
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[Table 1], [Table 2], [Table 3]