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Increase of lower esophageal sphincter pressure after osteopathic interventionon the diaphragm in patients with gastroesophageal reflux

R. C. V. da Silva,1 C. C. de S,3 . O. Pascual-Vaca,1,2 L. H. de Souza Fontes,3

F. A. M. Herbella Fernandes,4 R. A. Dib,3 C. R. Blanco,1,2 R. A. Queiroz,1 T. Navarro-Rodriguez3

1Escuela de Osteopatia de Madrid, Madrid, and 2Department of Physiotherapy, University of Seville, Seville,Spain; and 3Department of Gastroenterology, University of So Paulo, and 4Department of Surgery, EscolaPaulista de Medicina, Federal University of So Paulo, So Paulo, Brazil

SUMMARY. The treatment of gastroesophageal reflux disease may be clinical or surgical. The clinicalconsists basically of the use of drugs; however, there are new techniques to complement this treatment,osteopathic intervention in the diaphragmatic muscle is one these. The objective of the study is to comparepressure values in the examination of esophageal manometry of the lower esophageal sphincter (LES) beforeand immediately after osteopathic intervention in the diaphragm muscle. Thirty-eight patients with gastro-esophageal reflux disease 16 submitted to sham technique and 22 submitted osteopathic technique wererandomly selected. The average respiratory pressure (ARP) and the maximum expiratory pressure (MEP) of theLES were measured by manometry before and after osteopathic technique at the point of highest pressure.Statistical analysis was performed using the Students t-test and MannWhitney, and magnitude of thetechnique proposed was measured using the Cohens index. Statistically significant difference in the oste-opathic technique was found in three out of four in relation to the group of patients who performed the shamtechnique for the following measures of LES pressure: ARP with P = 0.027. The MEP had no statisticaldifference (P = 0.146). The values of Cohen d for the same measures were: ARP with d = 0.80 and MEPd = 0.52. Osteopathic manipulative technique produces a positive increment in the LES region soon afterits performance.

KEY WORDS: gastroesophageal reflux, lower esophageal sphincter, osteopathic manipulation, treatment.

INTRODUCTION

Gastroesophageal reflux disease (GERD), althoughnot considered a severe illness,1 is one of the mostcommon disorders of the gastrointestinal system.2

It has a great medical-social importance, with a highand growing prevalence. It is the cause of variousesophageal symptoms37 and extraesophageal symp-toms,8,9 having a negative impact on quality of life10,11

with reflex on the economy of the society.12,13

The LES and the crural diaphragm represent theintrinsic and extrinsic sphincters, respectively. Theyare anatomically overlaid and anchored one to theother through the phrenoesophageal ligament.14

During contraction of the crural diaphragm, anincrease of the LES pressure occurs,15 contributing toa three- to four-fold growth of the pressure in the

Address correspondence to: Dr Tomas Navarro-Rodriguez,MD, PhD, Department of Gastroenterology ClinicalGastroenterology, University of So Paulo School ofMedicine, Avenue Dr Eneas Carvalho de Aguiar, 255 ICHC,9th floor, office 9159, So Paulo 05403-000, Brazil.Email: tnavarro@usp.brConflict of Interest: Guarantor of the article: TomasNavarro-Rodriguez, MD, PhDSpecific author contributions: Study conductance, databasedevelopment, data analysis, and manuscript writing: RafaelCorra Vieira da Silva; Study conductance and databasedevelopment: Cludia Cristina de S; Protocol development,study conductance, database development, and data analysis:Luiz Henrique de Souza Fontes, Fernando Augusto MardirosHerbella Fernandes, and Ricardo Anuar Dib; Datainterpretation and manuscript writing: ngel OlivaPascual-Vaca, Cleofs Rodriguez Blanco, and Rogerio AugustoQueiroz; Protocol development, technology development,supervision of study conductance, data interpretation, andmanuscript writing: Tomas Navarro-RodriguezFinancial support: NonfinancialPotential competing interests: None

Diseases of the Esophagus (2013) 26, 451456DOI: 10.1111/j.1442-2050.2012.01372.x

2012 Copyright the AuthorsJournal compilation 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus 451

gastroesophageal junction (GEJ) region.16 In addi-tion, both the LES and the diaphragm relax during ashort period of time to allow passage of the foodbolus during esophageal peristalsis.17

Investigation using high-resolution manometryreviewed the diaphragmatic function in patients withand without gastroesophageal reflux (GER) and evi-denced a diaphragmatic deficient function in patientswith GER, as shown by the reduced increase of theinspiratory pressure of the GEJ.18

Nevertheless, the inspiratory muscles, includingthe diaphragm, are morphologically and functionallyskeleton muscles and therefore should respond totraining just like the gait muscles, if submitted to anappropriate stimulus. It has already been demon-strated that the diaphragm increases its thicknesswhen a resistance is applied against it during weight-lifting training.17 Downey et al. reported an 812%increase in the diaphragm thickness during con-traction after muscular inspiratory post-training for4 weeks.19

Within this background and considering otherstudies that have shown good results with the osteo-pathic manipulative treatment in visceral dysfunc-tions,2022 the study of this kind of therapeuticapproach has shown to be important to be added tothe GERD conservative treatments and maybe, avoidsurgery.

Many authors have shown the fundamentalimportance of the diaphragm within the GEJ struc-tures, with an important role in the sphincter mecha-nism against reflux.16,18,2325 Therefore, we shall usethe lower esophageal sphincter (LES) manometricstudy to review the immediate repercussion of thediaphragmatic stretching technique widely used byosteopathicians to obtain equilibrium of the dia-phragm functions in the mechanism against GERcompared with the placebo technique.

MATERIALS AND METHODS

Patients

All patients above 18 years old, regardless of gender,referred to the Laboratory of Digestive MotilityInvestigation of the Gastroenterology Service of Hos-pital das Clinicas of the University of So PauloSchool of Medicine to undergo an esophageal mano-metric examination, who were released with a GERDdiagnostic, were randomly screened and invited toparticipate in the study.

Studied groups

Patients were randomly allocated to two groups:group O (osteopathy) undergoing the diaphragmstretching technique, which included 22 individuals,

and group P (placebo control) who went throughthe placebo technique and included 16 patients.

Diaphragm stretching techniqueThe diaphragm stretching technique has been per-formed by only one of the investigators, who was notin charge of data collection nor interpretation of themanometry measurements. The protocol includes thetechnique suggested by Coster and Pollaris26 modifiedas follows: the position of the patient laying back(supine) with the legs bent and the feet against thebed. A total of eight deep respiratory maneuvers wereperformed in two steps: first step four deep respira-tions, in which the inspiration and expiration move-ments are exacerbated by the investigator throughmanual contact on the lower rim of the last ribs;second step: four deep respirations, in which, duringthe expiratory phase, the investigator will sustain theribs grid using the same contact to avoid the descentof the thoracic cage during the expiratory phase.During the performance of the technique, the inves-tigator would encourage and coordinate deep breath-ing of the patients through voice command.

Sham techniqueThe sham technique was performed by the sameinvestigator who performed the diaphragm stretchingtechniques. Patient lying back with the legs bent andfeet against the bed. The investigator maintained onehand in contact on the patients sternum and theother hand on the abdomen, next to the gastricregion. The patient had to produce the same eightdeep breathings, during which the same voice com-mands of the diaphragm technique were given;however, the investigators hands only maintain aphysical contact with the patient without exerting anypressure, or putting any incentive or restriction to themovements of the thoracic cage.

Esophageal manometryThe esophageal manometry exam was performed bya specialized physician using the device Alacer Mul-tiplex BP 108 (Alacer Biomedica, So Paulo, Brazil).The manometric exam was performed normally bythe dedicated physician who, after reaching thegastric cavity, coordinated so that the probe waspulled each 0.5 cm throughout the extension of theLES. The objective was to obtain a more faithfulcharacterization of all its extension and pressurecharacteristics. After the end of the esophageal bodymanometric exam, the probe was reintroduced in thepatients stomach, and the technique was performedby the osteopathologist in charge. After 20 seconds,the probe was pulled again each 0.5 cm throughoutthe extension of the LES, and the data were imme-diately recorded after performing the diaphragmstretch or sham techniques.

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Selection of the points studied

After the end of the exam, the physician measured theaverage respiratory pressure (ARP) and maximumexpiratory pressure (MEP)27 and chose the highestpoint (HP) and the mean between all points beforeand immediately after the osteopathic interventionor application of the placebo technique. In case ofdispute as to which would be the best method tomeasure the LES, excluding the diaphragm pressureforce.

Statistical analysis

Before analyzing the data was performed transforma-tions of each variable in order to facilitate calcula-tions and understanding of the problem. We chose tochange based on differences in values as follows: Thevariables ARP from the HP pre-intervention andpostintervention of the group O gave rise to the vari-able Difference (pr-ps) of ARP (HP) of the groupO, the variables ARP from the HP pre-intervention,and postintervention of the group P gave rise to thevariable Difference (pr-ps) of ARP (HP) of thegroup P, and so on. Then, analyze the data to findpossible differences between the responses of twogroups are summarized in comparing these newvariables and determine whether they are statisticallydifferent.

The next step was to analyze the distribution ofeach group of new variables to correctly define whichthe best test to use is. For this, it took severalQuantile-Quantile (QQ) plots more specifically,normal QQ plots. Non-parametric tests (MannWhitney) were adopted for those variables that didnot comply with the homogeneity criteria of thevariance and/or normal distribution. For all othervariables, the Students t-test was except for thecomparison of the proportion of men and women ineach group, for which an exact Fisher test with 95%significance level was used. In addition to the infer-ential analysis, as a way to quantify the magnitude ofthe difference observed among two groups, the mag-nitude of the effect was determined (effect size:Cohen d), a rate that measures the magnitude of the

effect of the proposed technique.28 The d values forsmall, medium, and large magnitude effects are 0.2,0.5, and 0.8, respectively, and the medium and largevalues are considered as having clinical importance.28

RESULTS

A total of 38 patients were assessed, of which 25 wereof the female gender (65.7%). The mean age, weight,height, and body mass index (BMI) of the group O(osteopathy) was 49.5 years of age, 67.3 kg, 1.61 m,and BMI 25.72, respectively. And that of the placebogroup (group P) was 50.5 years of age, 61.8 kg,1.62 m, and BMI 23.52. The two groups were notdifferent as far as age, weight, BMI, and height areconcerned (tests t P > 0.21), as well as with regard tothe gender distribution (Table 1).

Variables of the LES pressure

In Table 2, we analyzed variables of the LESpressure in each group before and after theprocedures. All P-values were greater than 0.05;however, the null hypothesis cannot be rejected.In other words, all LES pressure variables maybe seen as normally distributed and parametric(t-Student) being the tests suited to the task of groupcomparison.

ARP and MEP mean values

A summary of the mean values of ARP and MEP isshown in Table 3.

Table 1 Gender, age, and body mass index variation

Variable Placebo group Osteopathy group

Number 16 22Women/men 09/07 16/06Mean body mass index* 23.52 25.72Mean age (years)* 50.5 16.21 49.4 15.01

*P > 0.21.

Table 2 Variables of the LES pressure: at the point of maximum pressure (ARP and MEP pre-intervention and postintervention)

Statistical analysis

ARP pre ARP post MEP pre MEP post

Osteopathygroup

Placebogroup

Osteopathygroup

Placebogroup

Osteopathygroup

Placebogroup

Osteopathygroup

Placebogroup

Mean 20.04 25.74 21.87 22.14 12.03 16.88 14.57 15.51Standard deviation 8.07 15.29 9.70 18.25 5.76 12.90 8.13 18.03KolmogorovSmirnov Z 0.622 0.913 0.655 0.927 0.831 0.923 0.860 1.188P-value 0.834 0.376 0.784 0.357 0.495 0.362 0.451 0.119

ARP, average respiratory pressure; LES, lower esophageal sphincter; MEP, maximum expiratory pressure; post, postintervention;pre, pre-intervention.

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The values of d for small, medium, and large mag-nitude are, respectively, 0.2, 0.5, and 0.8, and themedium and large values are considered as havingclinical relevance.28 The values of Cohen d for thesemeasurements were: ARP - d = 0.80 and MEP - d =0.52. This demonstrates that the difference of themeasurement of ARP between the groups is of highmagnitude, considered clinically relevant by Cohen28

(Table 3).

Difference (prepost) of ARP (HP) between groupsO and P

Both variables arise from normal distributions. Inthis case, the Students t-test was used to comparethe two groups with regard to this variable. Themean difference of the ARP (HP) in the group Owas 1.84 + 5.20 standard deviation (SD) and themean of the difference of ARP (HP) in the group Pwas -3.61 + 8.05 SD (P = 0.027). In reviewing eachgroup mean and considering that these are variablesrelated to the difference between two other values(prepost), it may be stated that in the group O, thevalue of ARP postintervention is generally greaterthan the ARP value postintervention in the group P(Table 4).

Difference (prepost) of ARP (mean between allpoints) between groups O and P

The MannWhitney test was used to compare thetwo groups regard to this variable. The median dif-ference of ARP (mean between all points) in group Owas 3.70, and the median difference of ARP (mean

between all points) in group P was -1.85 (P = 0.0066).In reviewing each group median, it may be stated thatin the group O, the value of ARP postintervention isgenerally greater than the ARP value postinterven-tion in the group P (Table 4).

Difference (prepost) of MEP (HP) between groupsO and P

Both variables arise from normal distributions. Inthis case, the Students t-test was used to compare thetwo groups with regard to this variable. The meanof the difference of MEP (HP) in the group O was2.53 4.75 SD and of group P -1.36 9.48 SD(P = 0.146). Given the high value of P (>0.05), wecannot say that the groups differed in terms of vari-able MEP (HP). Although the means are very differ-ent, the high SD value in group P also implies a largevariation, which may be why no differences werefound between the groups in this analysis (Table 4).

Difference (prepost) of MEP (mean between allpoints) between groups O and P

The MannWhitney test was used to compare thetwo groups with regard to this variable. The mediandifference of MEP (Mean between all points) ingroup O was 2.69, and the median difference of MEP(mean between all points) in group P was -0.82 (P =0.0493). Analyzing the value of P (

DISCUSSION

The assumption of this study was that the dia-phragm stretching maneuver largely used by osteo-pathicians to obtain the functional equilibrium ofthis muscle fosters increase of the LES pressureimmediately after performing the maneuver, as aconsequence of an increased strengthening of thediaphragm muscle. Among the major findings isthe observed LES increased pressure in patientswho underwent the osteopathic technique whencompared with the placebo technique for all themeasurements investigated.

Another interesting outcome was the responsewith regard to the effect size that demonstrated theclinical relevance in connection with the majority ofthe variables reviewed.

Our results demonstrated that there was anincrease of 927% of the LES pressure in patientswho performed the osteopathic maneuvers, while inthe group of patients who did not perform themaneuvers, a reduction of that pressure was observed(Table 5). These results are quite close to those ofother investigators, who indicated that during thecontraction of the crural diaphragm, an increase ofthe LES pressure occurs,15 contributing for a three- tofour-fold increase in the pressure in the GEJ region,16

as well as an increase from 8% to 12% in the dia-phragm thickness during muscular inspiratory post-training contraction for 4 weeks;19 this is differentfrom our study that showed an increase of the LESpressure.

Our data are of extreme clinical importance and ofhigh practical relevance because in the assessment bythe LES esophageal manometry, we assessed theregions of the LES having greater pressure either byARP or MEP, and not the average of all the sphincterassessment. In addition to supporting the beliefs ofthe osteopathic community and what they observeclinically, nevertheless, we cannot say that a completeosteopathic treatment has been conducted for thediaphragm or even for the GEJ; this characterizes ourinvestigation only as an osteopathic technique studyand not as a complete osteopathic manipulative treat-ment study. However, the fact that the use of onlyone single technique for one of the main GEJ struc-

tures had a positive influence on the increase of theLES pressure was seen with great enthusiasm by allthe investigators involved.

No other similar study was found in the literatureand our findings appear important in connection withthe potential clinical applications of the osteopathictreatment for GERD and consequently its benefit asco-adjuvant in the clinical or surgical treatment ormaybe even in the future as a single therapy for somekinds of specific patients. It is still not possible to sayif these changes are durable, which requires continu-ation of the research in other centers and with a largernumber of patients.

However, the despite we not analyzed if therewere changes in symptoms after application of thetechnique, subjects treated with this osteopathic dia-phragm stretching technique often report an improve-ment in areas such as heartburn and reflux, whichcorresponds with the values of large and mediumclinical effect (according to Cohens statistic) achievedin the study variables.

CONCLUSION

The osteopathic manipulative technique used toproduce the diaphragm functional equilibrium causesa positive increment, statistically significant, in theLES region soon after it is performed.

Acknowledgments

We wish to thank the Gastroenterology Disciplineof University of So Paulo School of Medicine andthe Escuela de Osteopatia de Madrid for the supportand encouragement of the study conducted.

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Table 5 Difference between the values ARP (HP) and MEP (HP)postintervention in relation to pre-intervention values in thegroups placebo and osteopathic (%)

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Osteopathy group(n = 22)

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