Mechanisms underlying the antireflux effect of Nissen fundoplication in children

Mechanisms By Hisayoshi

Kawahara,

Underlying the Antireflux Effect of Nissen Fundoplication in Children

Kenji Imura,

Makoto

Yagi, Akihiro Osaka,

Yoneda,

Hideki

Soh, Yuko Tazuke, and Akira Okada

Japan

Background/Purpose: It is reported that the main mechanism responsible for gastroesophageal reflux (GE!+ is transient lower esophageal sphincter (LES) relaxation in children. However, the effect of Nissen fundoplication on transient LES relaxation has not been investigated in children. This study examined the effect of Nissen fundoplication on motor patterns of the LES in children with pathological GER.

significantly (pre, 21 number of transient from 13 + 4 to 7 2 during swallow-induced relaxation increased mm Hg and from 0 2

Methods: Esophageal manometry and pH were recorded concurrently for 2 hours after administration of apple juice (IO mL/kg). In seven children documented to have pathological GER by prolonged esophageal pH monitoring (%time pH less than 4.0 > 5.0), studies were performed preoperatively and 1 to 3 months after surgery.

Conclusions: Our findings suggest the antireflux effects of Nissen fundoplication may be based on changes of LES motor patterns that result in incomplete LES relaxation and reduction of the number of transient LES relaxation. J Pediatr Surg 33:7618-1622. Copyright o 1998 by W.B. Saunders Company.

Results: Nissen fundoplication virtually eliminated reflux in all patients. Percentage of time pH was less than 4.0 reduced from 15 ? 9 to 0 ? 0. Basal LES pressure did not change

INDEX WORDS: tion, transient

YMF’TOMATIC gastroesophageal reflux (GER) is a common problem in infants and young children, but the mechanical events that lead to its intermittent occurrence are poorly understood. It has been proposed that GER occurs mainly because of weak steady state lower esophageal sphincter (LES) pressure, which allows the sphincter to be overcome easily by spikes of intragastric pressure generated by straining.Q It was suggested that at least some reflux episodes in children occur during periods of transient LES relaxation.3,4 We have reported recently that the main mechanism responsible for GER is transient LES relaxation in children with or without pathological reflux.5 Nissen fundoplication is the most common surgical procedure for children with pathological GER,6 the efficacy of which has been established by clinical and endoscopic findings and by esophageal pH monitoring.7 However, the effect of Nissen fundoplication on the

S

From the Department of Pediatric Surgery Osaka University Medical School and the Department of Pediatric Surgery, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan. Presented at the 31st Annual Meeting of the Pacijc Association of Pediatric Surgeons, Maui, Hawaii, June 9-13, 1998. Address reprint requests to Hisayoshi Kawahara, MD, Department of Pediatric Surgery, Osaka University Medical School, 2-2 Yamadaoka Suita, Osaka, Japan. Copyright 0 1998 by WB. Saunders Company 0022-3468/98/3311-0008$03.00/O 1616

5 10 mm Hg vpost, 27 + 9 mm Hg). The LES relaxation reduced significantly 7, and the mean nadir LES pressures LES relaxation and transient LES significantly from 1 ? 1 mm Hg to 13 ? 5 0 mm Hg to 11 2 7 mm Hg, respectively.

Gastroesophageal lower esophageal

reflux, Nissen sphincter

fundoplicarelaxation.

control of reflux is not well investigated in terms of how it works.* The precise manometric evaluation of the LES function is only possible by the use of the positiontolerant sleeve sensor, which monitors LES pressure for hours, thus allowing reliable capture of motor events associated with spontaneous reflux episodesgJO This study was aimed to examine the effect of Nissen fundoplication on motor patterns of the LES in children who have pathological GER. MATERIALS

AND

METHODS

Patients Ten children with symptomatic GER were studied prospectively in 1996 and 1997. Children who had any prior esophageal surgery or diaphragmatic surgery, or those who had structural abnormalities of the esophagus other than hiatus hernia, were excluded. In three children with cerebral palsy, manometric tracings obtained preoperatively were not analyzable because of their body movement, crying, and strains, including coughing, during the study. Therefore, the analysis was performed in manometric tracings of seven children with a mean age of 41 -C 25 months. All patients had intractable reflux symptoms. whtch were mainly emesis and repeated respiratory infections. They showed abnormally increased esophageal acid exposure, which was determined as percent time of esophageal pH of less than 4.0 over 5.0 by 24-hour esophageal pH monitoring (Mark III; Synectics Med, Stockholm, Sweden). Four patients had cerebral palsy, and the remainder showed developmental delay for their age. In all patients, Nissen fundoplication associated with a Stamm gastrostomy was performed through laparotomy by one of the authors. The 360” fundal wrap was fixed to the esophageal hiatus, which was approximated with unabsorbable sutures. JournalofPediatric

Surgery,

Vol33,

No 11 (November),

1998: pp 1618-1622

MECHANISMS

OF NISSEN

1619

FUNOOPLICATION

RESULTS

Protocol and Manometric Procedures Studies were carried out preoperatively and 1 to 3 months after Nissen fundoplication. Informed consent was obtained from patients’ parents before the study. Patients fasted for at least 4 hours, and all drugs were withheld 24 hours before the study except anticonvulsants. Esophageal manometry and pH were monitored for 2 hours after intake of apple juice (10 mL/kg). No sedation was given. A 7-channel manometric assembly for pharyngeal, esophageal body, LES, and gastric pressure monitoring and a pH electrode were passed transnasally. Measurements were performed with the child recumbent, either on a bed or on the parent’s lap. Two Dentsleeve miniature manometric assemblies (Dentsleeve Pty, Adelaide, Australia) were used, which had spans between the pharyngeal and gastric side holes of 16 and 23 cm. LES pressure was recorded with 4.0- or 5.0-cm long sleeve sensors, the cross sections of which were miniaturized in the two span assemblies (diameter, 25 mm). An antimony pH electrode (Synectics Med) was used for distal esophageal pH recording, the sensor of which was located 3 cm above the location of the LES determined by manometry. The manometric assembly was perfused with a low compliance infusion pump (Amdorfer Medical Specialties, Greendale, WI). The sleeve and the side holes at the stomach and the esophageal body were perfused at 0.3 mL/min, and the pharyngeal side hole was at 0.2 mL/min. Monitoring of occurrence of pharyngeal pressure waves was usually adequate as signals of swallowing. The position of the sleeve relative to the LES was adjusted by pressure patterns seen in the respective recording side hole at the proximal and distal sleeve margin. Calibration of the pH electrode was checked m buffer before and after each study. The combined data of manometry and pH-metry were recorded using Polygraph motility measurement system (Synectics Med) including a personal computer (Gateway, Sioux City, SD).

Data Analysis The 2-hour postprandial period was analyzed. Mean values of end-expiratory basal LES pressure were determined visually from every 15th minute of tracing in each study using intragastric pressure as the reference. If this segment of the tracing was uninterpretable because of crymg or restlessness, the first interpretable minute after was used. Separate mean value was derived from these samples for each patient. Reflux episodes were scored when esophageal pH level dropped to below 4 for at least 4 seconds. LES relaxation was originally defined as an abrupt pressure reduction equaled or exceeded 1 mm Hg/sec from over 2 mm Hg to within 2 mm Hg of intragastric pressure.5 Transient LES relaxation was defined as an LES relaxation lasting longer than 5 seconds in which no swallow was scored within 5 seconds before and 2 seconds after the onset of the relaxation.s LES relaxation was defined differently for the postoperative studies, because LES pressure rarely reduced to within 2 mm Hg at swallowing. The nadir pressure relative to intragastric pressure during the LES pressure reduction induced by spontaneous swallowing was scored at 10 testable single swallows, the mean value of which was obtained in each patient. A testable single swallow was separated by at least 15 seconds from prior or subsequent swallows. When the LES pressure reduction reached less than (mean + SD) of the nadir pressure of LES pressure reduction induced by testable swallows, this LES pressure reduction was determined as an LES relaxation for the postoperative study. Data in the text are given as mean and SD of the mean. Statistical analysis was carried out with StatView for Macintosh (Abacus Concepts, Inc, Berkeley, CA). Tests for statistically significant differences between data were analyzed by Wilcoxon’s signed rank test unless specified otherwise. A P value of less than .05 was considered as significant in all analyses.

Symptoms related to gastroesophageal reflux were effectively controlled after the operation. Percent time of esophageal pH less than 4.0 measured in 24-hour esophageal pH monitoring decreased from 15 + 7 to 0 + 0 by surgery. Percent time of esophageal pH less than 4.0 and total number of reflux episodes was reduced significantly from 15 2 9 to 0 + 0 and 16 k 8 to 0 ? 0, respectively, in esophageal pH monitoring concurrently carried out with manometry. Basal LES pressure did not change significantly, which was 21 ? 10 mm Hg before and 27 5 9 mm Hg after the operation (paired t test, Fig 1). The number of the occurrence of transient LES relaxation was reduced from 13 k 4 to 7 + 7 during the 2-hour study period (paired t test, Fig 2). Duration of transient LES relaxation did not change, which was 14 ? 3 seconds before and 12 + 2 seconds after the operation. The nadir pressure of the LES relaxation induced by testable swallows increased significantly from 1 2 1 mm Hg to 13 -+ 5 mm Hg (Fig 3). The nadir pressure of transient LES relaxation also increased significantly from 0 + 0 mm Hg to 11 2 7 mm Hg (Fig 3). No significant difference was noted between the nadir pressure of the LES relaxation induced by testable swallows and that of transient LES relaxation before and after the operation (Analysis of Variance, Fig 3). Figure 4 demonstrates sample tracings of transient LES relaxation of a 7-year-old boy with cerebral palsy before and after the fundoplication.

Basal LESP mmHg

50 1

r-----Y

0Before fundoplication

After fundoplication

Fig 1. Change of basal LES pressure before and fundoplication. ns, no statistically significant difference; esophageal sphincter pressure.

after Nissen LESP, lower

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KAWAHARA

TLESR

Before fundoplication Fig 2. and after sphincter

After

fundoplicstlon

Change in the occurrence of transient LES relaxation before Nissen fundopiication. TLESR, transient lower esophageal relaxation.

DISCUSSION

For a long time basal LES pressure over a certain level has been assumed to be a key factor in the prevention of GER.‘J However, in our previous study,5 the majority of acid reflux episodes (>80% of all reflux episodes) occurred during complete LES relaxation, during which the high pressure zone at the gastroesophageal junction was abolished. Recording of swallowing showed that the majority of these relaxations were not triggered by swallowing. The time pattern of these relaxations and the associated patterns of pharyngeal and esophageal body motility just before these relaxations had the distinctive pattern of transient LES relaxation. These findings were shown by the novel method using combined manometric Nadir Pressure mmHg 20

p < 0.05

I

I

p-zo.05 I

I

12 8 1

After fundoplicatlon Fig 3. Mean (+SD) nadir pressures during swallow-induced transient LES relaxations before and after Nissen fundoplication. TLESR, transient lower esophageal sphincter relaxation.

or

ET AL

and pH recordings with miniaturized Dentsleeve manometric assemblies. In contrast to previous reports,5Ji we investigated the mechanisms of action of fundoplication by examining its effects on LES motor function. Our results suggest that antireflux effects of Nissen fundoplication are not associated with an increase in basal LES pressure, but are associated with reduction of the occurrence of transient LES relaxation and an increase in the nadir pressure during swallow-induced or transient LES relaxations. Data obtained in adult patients using similar procedures are conflicting regarding an increase of basal LES pressure after Nissen fundoplication.12-14 However, from a clinical point of view, an increase in basal LES pressure is not necessarily related to symptomatic improvement after the operation.12J5 Presumably, influence of the fundoplication on basal LES pressure is not relevant to the effect of the operation. Although the definition of transient LES relaxation might be controversial in the postoperative study, LES relaxations scored as transient LES relaxation postoperatively were with its distinctive motor profile in the esophageal body we had reported previously.5 The finding that the fundoplication reduced the number of transient LES relaxations is similar to that reported in adult patients.12J4 The mechanism by which the fundoplication reduced the occurrence of transient LES relaxations remains unknown. It is presumed that making fundal wrap may influence the distensibility of the gastric cardia,12J4 which is the most potent area for triggering of transient LES relaxation.16J7 The findings obtained in the present study suggest that the strategy for treatment of GER in children should be reevaluated. What is important, and has been missing in the treatment, is to reduce the frequency of transient LES relaxation rather than to augment basal LES pressure by prokinetic agents or surgery. To upgrade the method of fundoplication for children with symptomatic GER, we believe that it is crucial to know how to control triggering of transient LES relaxation appropriately. Our operative procedures made most of LES relaxations incomplete, which could be related to causes of postoperative complications such as gas bloat syndrome and dysphagia. Because only three patients were able to take food orally in our study, clinical evaluation regarding passage in the neogastroesophageal junction was limited to these patients. However, none of them showed postoperative dysphagia. Our finding regarding incomplete transient LES relaxation after the operation is similar to that reported in adult patient studies.12J4 However, Ireland et all2 demonstrated that the proportion of complete relaxations accompanied by reflux fell substantially after their fundoplication. This means that incompleteness of LES relaxation is not the sole mechanism preventing GER during transient LES relaxation,

MECHANISMS

OF NISSEN

FUNDOPLICATION

Fig 4. Sample tracings of transient LES relaxation before (top) and after (bottom) Nissen fundoplication. LES relaxation. Note incomplete transient LES relaxation after the fundoplication in contrast to transient was abolished completely before the fundoplication.

1621

Arrows show the onset of transient LES relaxation in which LES pressure

1622

KAWAHARA

and there may be other effects of the fundoplication on LES antireflux functions. Our findings suggest the antireflux effects of Nissen fundoplication may be based on changes of LES motor patterns that result in incomplete LES relaxation and reduction of the number of transient LES relaxations. Further study will contribute to establishment of more

ET AL

physiologically appropriate fundoplications in children with intractable reflux, especially in neurologically impaired children. ACKNOWLEDGMENT The authors thank John Dent, Gastrointestinal Medicine, Royal Adelaide Hospital, for his critical comments and continuous support.

REFERENCE 1. Hebra A, Hoffman MA: Gastroesophageal reflux in children. PediatrClinNorthAm40:1233-1251,1993 2. Boix-Ochoa J: The physiologic approach to the management of gastric esophageal reflux. J Pediatr Surg 21:1032-1039, 1986 3. Werlin SL, Dodds WJ, Hogan WJ, et al: Mechanisms of gastroesophageal reflux in children. J Pediatr 97:244-249, 1980 4. Cucchiara S, Bortolotti M, Minella R, et al: Fasting and postprandial mechanism of gastroesophageal reflux in children with gastroesophageal reflux disease. Dig Dis Sci 38:86-92, 1993 5. Kawahara H, Dent J, Davidson G: Mechanisms responsible for gastroesophageal reflux in children. Gastroenterology 113:399-408, 1997 6. Fonkalsrud EW, Ament ME, Berguist W: Surgical management of the gastroesophageal reflux syndrome in childhood. Surgery 97:42-48, 1985 7. Tumage RH, Oldham KT, Coran AG, et al: Late results of fundoplication for gastroesophageal reflux in infants and children. Surgery 105:457-464, 1989 8. Mittal RK: Do we understand how surgery prevents gastroesophageal reflux? Gastroenterology 106:1714-1715, 1994 9. Dodds WJ, Stewart ET, Hogan WJ, et al: Effect of esophageal movement on intraluminal esophageal pressure recording. Gastroenterology 67:592-600, 1974

10. Dent J: A new technique for continuous sphincter pressure measurement. Gastroenterology 71:263-267, 1976 11. Arana J, Tovar JA, Garay J: Abnormal preoperatrve and postoperative esophageal peristalsis in gastroesophageal reflux. J Pediatr Surg 21:711-714, 1986 12. Ireland AC, Holloway RH, Toouli J, et al: Mechanisms underlying the antireflux action of fundoplication. Gut 34:303-308, 1993 13. Breumelhof R, Timmer R, Nadorp JHSM, et al: Effects of Nissen ftmdoplication on gastro-oesophageal reflux and oesophageal motor function. Stand J Gastroenterol30:201-204, 1995 14. Johnsson F, Holloway RH, Ireland AC, et al: Effect of fundoplication on transient lower oesophageal sphincter relaxation and gas reflux. Br J Surg 84:686-689, 1997 15. Fonkalsrud EW, Ament ME, Byrne WJ, et al: Gastroesophageal fundoplication for the management of reflux in infants and children. J Thorac Cardiovasc Surg 76:655-664, 1978 16. Strombeck DR, Griffen DW, Harrold D: Eructation of gas through the gastroesophageal sphincter before and after limiting distension of the gastric cardia or infusion of a B-adrenergic amine in dogs. Am J Vet Res 50:751-753, 1989 17. Franzi SJ. Martin CJ, Cox MR, et al: Response of canine lower oesophageal sphincter to gastric distension. Am J Physiol 259:G380G385,1990