Background: To explore the effect of single oral dose of esomeprazole 20 mg, administered a night before surgery, on intragastric pH and volume in adult patients undergoing elective surgery by excluding cases contaminated with duodenogastric refluxate.Patients and Methods: This prospective, triple blind, randomised and placebo controlled clinical trial was conducted to explore the effect of single oral dose of esomeprazole 20 mg, administered a night before surgery, on intragastric pH and volume on 120 adult inpatients of either sex, American Society of Anaesthesiologist physical status I-II, and aged 15–70 years. The patients in Group C (control) received placebo while Group E (Esomeprazole) received esomeprazole orally at 9.00 pm, the night before elective surgery.On the day of surgery, the gastric contents were aspirated with a large bore, multi-orifice gastric tube passed through an endotracheal tube placed blindly in the oesophagus after tracheal intubation and analysed for pH, volume and the presence of bile salts.Results: Thirty nine samples (33%) out of 117 were contaminated with duodenal contents. Duodenogastric reflux significantly affected pH and volume in Group C (p value 0.0003 and 0.0016) and E (p value 0.0401 and < 0.0001). Esomeprazole, after excluding samples contaminated with duodenal fluid, significantly increased pH (p  25 ml/kg) at the time of induction of anaesthesia excluding samples contaminated with duodenogastric reflux

Al-Saeed, A.H

Habib, S.S

Hussein, A

English

AJOL - African Journals Online

SAJAA 2008;14(5) • Sep/Oct                                                          39 ■ Original ResearchSAJAA 2008; 14(5): 39-42aHussein A, bAl-Saeed AH, cHabib SSa Department of Anaesthesiology, King Khalid University Hospital, Al-Riyadh, Saudi Arabiab College of Medicine and King Saud University Hospitals, King Saud University, Saudi Arabiac Department of Physiology, King Saud University, Saudi ArabiaCorrespondence to: Dr A Hussein, e-mail: draltaf94@yahoo.comEsomeprazole as a prophylactic agent for acidaspiration syndrome in adult patients undergoingelective surgery: A triple blind placebo controlledclinical trialABSTRACTBackground: To explore the effect of single oral dose of esomeprazole 20 mg, administered a night before surgery, onintragastric pH and volume in adult patients undergoing elective surgery by excluding cases contaminated with duodenogastricrefluxate.Patients and Methods: This prospective, triple blind, randomised and placebo controlled clinical trial was conducted toexplore the effect of single oral dose of esomeprazole 20 mg, administered a night before surgery, on intragastric pH andvolume on 120 adult inpatients of either sex, American Society of Anaesthesiologist physical status I-II, and aged 15–70years. The patients in Group C (control) received placebo while Group E (Esomeprazole) received esomeprazole orally at9.00 pm, the night before elective surgery.On the day of surgery, the gastric contents were aspirated with a large bore, multi-orifice gastric tube passed through anendotracheal tube placed blindly in the oesophagus after tracheal intubation and analysed for pH, volume and the presenceof bile salts.Results: Thirty nine samples (33%) out of 117 were contaminated with duodenal contents. Duodenogastric reflux significantlyaffected pH and volume in Group C (p value 0.0003 and 0.0016) and E (p value 0.0401 and < 0.0001). Esomeprazole, afterexcluding samples contaminated with duodenal fluid, significantly increased pH (p <0.0001), decreased volume (p 0.0068)and the percentage of the patients (2.56% versus 30.76%) considered “at risk” compared with placebo (p 0.0015) accordingto the criteria defined (pH ≤ 2.5 and volume ≥ 25 ml).Conclusion: Esomeprazole 20 mg administered orally a night before elective surgery improved the gastric environment (pH< 2.5 and volume > 25 ml/kg) at the time of induction of anaesthesia excluding samples contaminated with duodenogastricreflux.IntroductionDuodenogastric reflux is the retrograde flow of duodenal contentsinto the stomach that then mixes with acid and pepsin.1 Hugeset al2 reported 33%, Raved et al3 8.98 % and Wolverson et al446% incidence of duodenogastric reflux in healthy subjects. Ourfirst aim was to determine whether or not duodenogastric refluxsignificantly affects gastric pH and volume.Esomeprazole, a proton pump inhibitor, is used in peptic ulcersand other acid dyspeptic disorders of the upper gastrointestinaltract in a dose of 20 mg orally once daily.5 The effect of a singleoral dose of esomeprazole 20 mg on preoperative gastric fluidpH and volume has not yet been studied. The second aim ofthis study was to determine whether or not a single oral doseof esomeprazole 20 mg, administered a night before surgery,is effective in increasing the pH ≥ 2.5 and decreasing volume≤ 0.4 ml/kg or 25 ml in adult patients undergoing electivesurgery by excluding those cases contaminated withduodenogastric reflux, if duodenogastric reflux significantlyaffects pH and volume of gastric contents.Patients and methodsThe protocol of the study was approved by the Research andEthics Committee and written, informed patient consent wasobtained. One hundred and twenty patients (120) of AmericanSociety of Anaesthesiologists (ASA) physical status I-II, aged15–70 years scheduled for elective surgery under generalanaesthesia participated in the study.We excluded patients from our study known to have uppergastrointestinal disorders, the morbidly obese having a bodymass index (BMI) of more than 40 kg/m2, those receivingmedications known to affect the secretory and/or motor functionsof the stomach, difficult intubation, i.e. Mallampati class IVand/or mouth opening less than 5 centimetres and/or a thyromentaldistance less than 6.5 centimetres and/or history of documenteddifficult intubation, intestinal obstruction, parturients and DiabetesOriginal Research■ 40 SAJAA 2008;14(5) • Sep/OctMellitus. Patients who took the study drugs but their gastricaspirates showed bile acids due to duodenogastric reflux werenot included in the final statistical analysis while analysing pHand volume of gastric contents. We did not consider thesesamples as true gastric contents because in these samples alkalineduodenal fluid was mixed with acidic gastric contents.The patients were randomly allocated by sealed envelope methodto receive either esomeprazole 20 mg (n = 60) or placebo (n= 60) by oral route at 9.00 pm on the night before surgery. Allpatients also received oral diazepam 10 mg at the same time.On the pre-operative anaesthesia visit, the nature and purposeof the study was explained to all patients. According to thehospital policy, all patients were fasted from 12 midnightirrespective of the nature (solids or liquids) of the last mealtaken. Age, sex, weight, height, BMI, ASA physical status, andthe drug given were recorded for each patient. Before the startof anaesthesia, all patients were asked if they had been awareof any unusual feelings (side-effects) after taking the medications,the night before surgery.General anaesthesia was induced with injected fentanyl, propofol,and maintained with sevoflorane and air in oxygen. The lungswere ventilated taking care to avoid inflation of the stomach.Tracheal intubation was facilitated by rocuronium. Anotherendotracheal tube sized 8.5 mm internal diameter lubricatedwith paraffin liquid internally was passed in the oesophaguswith anterior displacement of the larynx. A predetermined lengthof orogastric tube (from xiphoid process to ear lobules and fromear lobules to nasal tip)6 (Jamjoom Medical Industries, Jeddah,Saudi Arabia) sized 16 F was passed through the oesophageallyplaced endotracheal tube7 into the stomach.Placement of the orogastric tube within the stomach wasconfirmed by auscultation over the epigastrium during introductionof 10–15 ml of air. Gastric fluid samples were collected by gentleaspiration with 60 ml of syringe by an investigator who wasunaware of the preanaesthetic medication. Aspirations wereattempted while the patients were held in supine and then inleft and right lateral positions.8 The orogastric tube was removedfollowed by an  oesophageally placed endotracheal tube. Anyproblem faced during inserting or removing the oro-oesophageallyplaced endotracheal tube or orogastric tube was also recorded.Gastric contents were visually inspected for the presence ofblood. The volume of gastric contents was measured withgraduated syringe and pH immediately with pH meter (Model215 version 3.4, Denver Instrument Company, United States).The pH meter was calibrated using standard buffers at pH valuesof 4.0, 7.0 and 9.20. This pH meter has a precision of 0.01 unitsover the entire pH range. A minimum of one millilitre volumeof gastric contents was sufficient for pH determination with pHmeter. Samples less than one millilitre were considered as nogastric contents because a minimum volume of one millilitre ofgastric contents was sufficient for pH- metery.Using bile salts as a marker for bile, we applied the qualitativeHay’s Sulphur test for the presence of bile salts. This test dependson the principal that bile salts have the property of reducingthe surface tension of fluids in which they are contained.9 Inthis test finely powdered sulphur is sprinkled upon the surfaceof cool (170C or below) liquid. If the sulphur remains floatingon the surface, bile salts are absent. On the other hand, if bilesalts are present the sulphur sinks down, sooner or later, inaccordance with their percentage. If bile salts are present in thefluid from 1:5000 (0.02% or 200μg/ml) to 1:10,000(0.01% or100μg/ml) sulphur at once begins to sink and is all precipitatedin two or three minutes; even in a dilution of 1:120,000 (0.0008% or 8.33 μg/ml) precipitation occurs.10Time since premedication, time since Nil per Os (NPO), pH,volume of gastric contents and the result of the Hay’s Sulphurtest were also recorded for each patient. On the basis of Hay'sSulphur test, we further divided Group C into Subgroups C-1and C-2 and Group E into Subgroups E-1 and E-2 to observePhysical characteristics of patients Group C Group E p value        n = 60 n = 60Age (years) 34.78 ± 13.44 34.08 ± 10.25 0.7490Sex 1.0000Male 30 (50%) 30 (50%)Female 30 (50%) 30 (50%)ASA physical status 0.3822 Class – I 49 (81.66%) 44 (73.33%)Class – II 11(18.33 %) 16 (26.66%)Weight (kilograms) 73.68 ± 15.28 78.47 ± 13.92 0.0753Height (centimetres) 161.31 ± 7.84 163.14 ± 10.63 0.2871Body Mass Index (kilograms/meter2) 28.40 ± 5.80 29.58 ± 5.43 0.2524Timings of eventsTime since premedication (minutes) 832.25 ± 136.51 812.50 ± 132.68 0.4232Time since NPO (minutes) 661.85 ± 138.03 636.33 ± 131.27 0.3016Table I: Physical characteristics of patients and timing of events. (Values are expressed either as mean ±SD or numbers (percentage)SAJAA 2008;14(5) • Sep/Oct                                                          41 ■ Original ResearchTable II: pH and volume of gastric contents. (Values are expressed as mean ± SD)Note: Samples mixed with blood (1 in Subgroup C-1 and 2 in Subgroup E-1 are not included.Group C-1 and Group E-1 represent contaminated samples with duodenogastric refluxate.Group C-2 and Group E-2 represent non-contaminated samples.Comparison between SubgroupsComparison of pH and volume between Group C-1 and Group C-2 (p value 0.0003 and 0.0016).Comparison of pH and volume between Group E-1 and Group E-2 (p value 0.0401 and < 0.0001).Comparison of pH and volume between Group C-2 and Group E-2 (p value <0.0001and 0.0068).Variables Group C Group E   n = 60 n = 60Group C-1 Group C-2 Group E-1 Group E-2n = 59 n = 39 n = 58 n = 39pH 3.06 ± 1.91 1.90 ± 0.47 4.75 ± 1.86 3.97 ± 1.66Volume (millilitres) 38.72 ± 33.52 19.60 ± 18.56 29.77 ± 32.98 10.70 ± 7.39Table III: Patients at risk according to defined criteria. (Values are expressed as numbers (percentage))Note: Samples mixed either with duodenal contents (39) or blood (3) are not included.Variables Group C -2 Group E -2 p valuen = 39 n = 39Patients with pH ≤ 2.5 37 (94.87 %) 11 (28.20 %)      <0.0001Patients with volume ≥25 ml 12 (30.76 %) 1 (2.56%) 0.0015Patients with pH ≤ 2.5 and volume ≥25 ml 12 (30.76%)            1 (2.56%) 0.0015the impact of duodenogastric refluxate on pH and volume ofgastric aspirates.Statistical analysis was performed using GraphPad Software, Inc,San Diego, United States, and results are expressed as absolutevalues (percentage) and mean ± standard deviation (SD).Statistical comparisons between Groups C and E were carriedout using two-tailed Student’s (unpaired) t test for age, weight,height, BMI, time since premedication, time since NPO, pH andvolume. Two-tailed Fisher’s exact test was applied for sex, ASAphysical status and risk of aspiration according to the criteriadefined by Roberts and Shirley11 (pH ≤ 2.5 and volume ≥ 0.4ml/kg or 25 ml). A p value of less than 0.05 was consideredstatistically significant.ResultsOne hundred and twenty (120) adult inpatients undergoingelective neuro (n = 1), thoracic (n = 8), urology (n = 11),gynaecological (n = 14), orthopaedic (n = 28) and general (n= 58) surgery were enrolled. Physical characteristics of patientsand timings of events are shown in Table I.There was no statistically significant difference between GroupsC and E regarding age, weight, height, BMI, duration sincepremedication and duration since NPO.We obtained gastric contents of all 120 patients. Three samples(2 in Group C and 1 in Group E) were mixed with blood.Hay’s test was performed on 117 samples and was positive in39 (33%) patients (20 in Group C – 9 males and 10 femalesand 19 in Group E – 9 males and 10 females). These samplesdo not represent true gastric contents and, therefore, wereconsidered as contaminated and are not included in finalstatistical analysis while analysing pH and volume of gastriccontents.Duodenogastric refluxate significantly affected the pH andvolume of gastric contents in Subgroups C-1 and C-2 (p value0.0003 and 0.0016) and in Subgroups E-1 and E-2 (p value0.0401 and < 0.0001) as shown in Table II.The pH and volume of all the Subgroups C-1, C-2, E-1 and E-2 are also shown in Table II. There was a statistically significantdifference between the Subgroups C-2 and E-2 (non-contaminatedsamples with duodenogastric refluxate) regarding pH (p 0.0118)and volume (p 0.0009) of gastric contents.The proportion (percentage) of the patients considered “at risk”of significant lung injury should aspiration occur is shown inTable III after excluding samples contaminated withduodenogastric refluxate.There was a statistically significant difference between theSubgroups C-2 and E-2 (p 0.0015) when both pH and volumewere combined according to the criteria defined.All patients were discharged from the hospital without anyproblem.DiscussionEsomeprazole is the last of the five proton pump inhibitors(omeprazole, lansoprazole, pantoprazole and rabeprazole)Original Research■ 42 SAJAA 2008;14(5) • Sep/Octavailable in the market for clinical use. Proton pump inhibitorsact by irreversibly blocking the hydrogen/potassium adenosinetriphosphatase enzyme system (the H+/K+ ATPase, or morecommonly just gastric proton pump) of the gastric parietal cell.The proton pump is the terminal stage in gastric acid secretion,being directly responsible for secreting H+ ions into the gastriclumen, making it an ideal target for inhibiting acid secretion.5Duodenal fluid consists of bile, pancreatic juice and smallintestine Brunner's gland secretion. All these secretions arealkaline in nature due to bicarbonate HCO3 – ions.12 Whenalkaline duodenal fluid flows in retrograde fashion, then it mixeswith acid and pepsin1 in the stomach and brings the pH towardsless acidity thus affecting pH and volume of gastric contentssimilar to oral ingestion of sodium citrate.In this current study, we passed an orogastric tube through anendotracheal tube passed blindly in the oesophagus. We obtaineda number of benefits by using this technique. Firstly, undergeneral anaesthesia the swallowing reflex is depressed and inan intubated patient, the oesophagus may be occluded byinflated endotracheal tube cuff and it can interfere with insertionof the orogastric tube. Secondly, this technique avoids findingthe upper oesophageally opening and coiling of the tube in themouth even after successfully passing the distal end of the tubeinto the stomach. Thirdly, moving of the orogastric tube in andout in different patient positions was very easy, thus causingpatients minimal trauma. Lastly, we prevented the entry ofpooled saliva into the pharynx during insertion, manipulationor removal of the orogastric tube.Our two samples were found to be mixed with blood due togastric mucosal entrapment. Gastric mucosal entrapment occursparticularly when air and fluid have been aspirated and thestomach is collapsed. Gastric mucosa is caught in the side holesof the stomach even with gentle suction. Bleeding may occurand blood can be found in the gastric tube thus giving the pHof blood mixed with gastric contents rather than pure gastriccontents.Blind aspiration via gastric tube is the common technique toaspirate the residual volume of gastric contents. In this presentstudy, total gastric volume may have been underestimated bythis method in each patient due to the functional divisions ofthe stomach into antral and fundal sacs.13 There is good agreementbetween gastric fluid volumes aspirated blindly and total volumesdetermined by fibreoptic gastroscopy (mean underestimation6 ml (22%); range 0–50ml).14ConclusionDuodenogastric reflux significantly affected both the pH andvolume of gastric contents. Preoperative oral esomeprazole 20mg administered the night before elective surgery increased thepH > 2.5 and reduced residual gastric content volume < 25 ml,possibly reducing the effects of pulmonary aspiration of gastriccontents.DeclarationWe conducted Project No. 05-501 entitled “Effect of single orallyadministered dose of proton pump inhibitors (omeprazole,esomeprazole, rabeprazole…etc. and/or H2 -receptor antagonists(ranitidine HCl, nizatidine, famotidine…etc) a night beforesurgery on the intragastric pH and volume in adult patientsundergoing elective surgery.” A triple blind placebo controlledclinical trial. This project was approved by the College ofMedicine Research and Ethics Committee King Saud University,Riyadh, Saudi Arabia. We studied five (5) proton pump inhibitors(omeprazole, lansoprazole, pantoprazole, rabeprazole andesomeprazole) and four (4) H2 - receptors antagonists (ranitidine,famotidine, nizatidine and cimetidine) with one design, aim andresearch methodology.AcknowledgementsThis was a self-sponsored project by the principal investigator.Authors are very thankful to the laboratory staff of ClinicalChemistry Unit, Nursing Department and Colleagues of Anaesthesiaand Surgical Departments of King Khalid University Hospital fortheir co-operation.References:1 Duodenogastric Reflux-induced (Alkaline) Esophagitis. Curr Treat OptionsGastroenterol 2004, 7:53-58.2 Hughes K, Robertson DAR, James WB. Duodenogastric reflux in normal anddyspeptic patients. Clin Radiol 1982; 33:461-466.3 Raved D, Kotsev I, Panaiotov P, Karageorgiev L, Georgiev M, Bozhanin D, andDimov D. The incidence of duodenogastric reflux and its relation to stomachand duodenal diseases. Khirurgiia (Sofiia).1990:43(4):61-64.4 Wolverson RL, Sorgi M, Mosimann F, Donovan IA, Harding LK, Alexander-Williams J. The incidence of duodenogastric reflux in peptic ulcer disease.Scandinavian Journal of Gastroenterology (Suppl.) 1984; 92:149-50.5 Joel J Heidelbaugh, Timothy T. Nostrant, Clara Kim, and Van Harrison R.American Family Physician 2003; 68:1311-8.6 McConnell EA. Ten problems with nasogastric tubes and how to solve them.Nursing1979; 9:78-81.7 Siegel IB, Kahn RC. Insertion of difficult nasogastric tube through a naso-esophageally endotracheal tube. Critical Care Medicine 1987; 15:876-877.8 Niinai H, Nakao M, Nakatani K, Kawaguchi R, Takezaki T and Kobayashi N.Significance of patient’s position in measuring gastric contents. Masui 1994;43(11): 1665-7.9 Joshi A. Rashmi. Identification of Substances of Biochemical Importance. In:Joshi A. Rashmi and Manju Saraswat (Eds). A Textbook of Practical Biochemistry.B. Jain Publishers. New Delhi. 2004; 51.10 John Dixon Mann. Physiology and Pathology of Urine. Griffin.1913:227.11 Roberts RB, Shirley MA. Reducing the risk of acid aspiration during caesareansection. Anesth Analg 1974; 53: 859- 868.12 Guyton AC. Secretory functions of the Alimentary Tract. In: Guyton & Hall(eds).Textbook of Medical Physiology.10th Edition. Philadelphia: W.B. Saunders,Inc. 2000; 738-753.13 Holdsworth JD, Johnson K, Mascall G, Roulston RG, Tomlinson PA. Mixingof antacids with stomach contents. Another approach to the prevention of theacid aspiration (Mendelson's). Anaesthesia 1980; 35:461-50.14 E. Søreide, J. A. Søreide, H. Holst-Larsen, and P. A. Steen. Studies of gastriccontent: comparison of two methods. Br. J. Anaesth. 1993; 70: 360–362.

Esomeprazole as a prophylactic agent for acid aspiration syndrome in adult patients undergoing elective surgery: A triple blind placebo controlled clinical trial

https://www.ajol.info/index.php/sajaa/article/download/62245/50255

Esomeprazole as a prophylactic agent for acid aspiration syndrome in adult patients undergoing elective surgery: A triple blind placebo controlled clinical trial

Abstract

Similar works

Full text

Available Versions

AJOL - African Journals Online