Gastroesophageal reflux disease (GERD) is a multifactorial disorder. The most frequent mechanism underlying gastroesophageal reflux is a transient relaxation of the lower esophageal sphincter (1). Other potential factors contributing to GERD include increased intra-abdominal pressure, reduced esophageal clearance and decreased gastric compliance. It is controversial whether a delay in gastric emptying plays a role in GERD (2,3).
Fundoplication, by either the open surgical or the laparoscopic approach, is the most widely used surgery for the treatment of GERD. Nissen fundoplication involves the mobilization and wrapping of the gastric fundus, leading to an extrinsic compression of the lower esophagus and the prevention of reflux.
The success of fundoplication has been ascribed partly to an improved gastric emptying (6-8). After surgery, up to 30% of patients experience complications, which include early satiety, postprandial fullness, nausea, vomiting, abdominal distension and dysphagia (9,10). The pathophysiology of such complications is uncertain. There have been a few studies (8,11,12) that have evaluated gastric accommodation, sensation and emptying in adults after fundoplication. Vu et al. (8) used the gastric barostat in 12 adult patients after Nissen fundoplication and compared the results with the findings on 12 healthy adults and 12 adults with GERD who did not undergo surgery. They found that post-Nissen patients had reduced postprandial gastric accommodation and accelerated gastric emptying, findings that were considered to contribute to postoperative dyspeptic symptoms. They speculated that the abnormalities resulted from the fundoplication and not from a vagus nerve injury or reflux per se. The pathophysiology of postfundoplication syndrome in children has not been well evaluated.
The aim of the present study was to define the effect of Nissen fundoplication on the gastric sensory and motor functions and to correlate such changes with clinical symptoms. To achieve this goal, we evaluated gastric sensation, compliance, motor function and symptoms in children both before and after surgery.
MATERIALS AND METHODS
We studied thirteen patients (12 male patients and 1 female patient; median age, 1 year; range, 0.5-18 years), who had failed medical treatment for GERD and were scheduled for Nissen fundoplication. Symptoms included breathing difficulties in 77%, vomiting in 69%, feeding intolerance in 23%, aspiration in 23% and failure to thrive in 7%. All patients had a gastrostomy placed before being enrolled in the study. Six had developmental delay. Nissen fundoplication was done through the open surgical approach in 6 and laparoscopic approach in 7. None of the subjects was subjected to pyloroplasty. All children underwent gastric barostat testing and gastric emptying study before fundoplication. Eight male patients (median age, 3 years; range, 10 months to 18 years) completed all the prefundoplication and postfundoplication evaluations within 3 to 7 months after surgery. Gastric barostat testing was not done in the other 5 patients for failure to follow-up. Gastric emptying was studied in 9 patients after surgery (Table 1).
All medications that were known to interfere with the sensory or motor functions of the gastrointestinal tract were stopped 4 days before the study. The subjects fasted for a period of 4 to 6 hours before the tests were started.
Solid-phase Gastric Emptying Measurement
Gastric emptying of solids in a mixed meal was measured by radionuclide scintigraphy before and after fundoplication. The subjects were fed with a meal of 2 scrambled eggs and 240 mL of milk. We measured the emptying value for solids in the presence of a liquid/solid meal in which the tracer is cooked into and binds to the egg. Anterior images of gastric activity were taken at a frequency of 1 image per minute for 120 minutes, starting after the ingestion. The acquisition was obtained dynamically, but the images were grouped in 5-minute segments. The percentages of gastric contents emptied were determined at 60, 90 and 120 minutes postingestion.
Gastric Barostat Measurements of Gastric Motility and Compliance
During barostat measurements, the subjects were seated in a semirecumbent position with the lower extremities just above the abdominal level. Placement of the barostat catheter was done without sedation.
An electronic barostat (G & J Electronics Inc, Toronto, Canada) was used to distend the stomach. A polyethylene bag of spherical shape with a maximum volume of 500 mL was tied to the end of a double lumen catheter, which was connected to the barostat. The gastric barostat catheter was introduced via the gastrostomy into the fundus. The barostat was used to measure gastric motor activity as a function of the changes in intragastric volume at a constant intragastric pressure. The barostat output was monitored continuously and recorded using a desktop computer. Isobaric distension was achieved by increasing the pressure in steps of 2 mm Hg each up to a pressure of 20 mm Hg. Each inflation cycle lasted for 3 minutes; the inflation was programmed to last for 1 minute, with 1 minute for deflation and 1 minute for rest. The minimal distending pressure (MDP) was defined as the first pressure level at which the intragastric volume was greater than 15 mL. Compliance (the ability of the organ to expand in response to pressure) was determined for each distension by plotting volume (y axis) versus pressure (x axis) and was defined as the slope of the curve.
Assessments of Perceptions of Pain and Fullness
Pain perception after distention (starting pressure of 0 mm Hg, increments of 2 mm Hg and final pressure of 20 mm Hg) was scored for each of the subjects on a scale of 0 to 7. The scale of perceived pain are the following: 0 = none, 1 = first sensation of discomfort, 2 = very mild, 3 = mild to moderate, 4 = moderate, 5 = greater than moderate, 6 = severe and 7 = unbearable pain. In very young or nonverbal children, the parents' assessment of their children's discomfort level was used.
The results of gastric barostat distensions are shown as the mean values for each patient and for each pre- and post-Nissen fundoplication values. The statistical significance of the differences between the test groups was analyzed using the nonparametric signed rank test (gastric emptying studies). Paired variables of gastric emptying and compliance prefundoplication and postfundoplication were analyzed using McNemar test. In all cases, a P value of less than 0.05 was considered to be statistically significant
This study protocol was reviewed and approved by the institutional review board of Children's Hospital in Columbus, Ohio before commencement. All participants in this study were enrolled, following written informed consent of their parents. Children older than 9 years signed an assent upon enrollment.
The post-Nissen mean MDP value was significantly higher than the pre-Nissen mean MDP value (10 mm Hg vs 3 mm Hg, P < 0.001) (Fig. 1). Gastric compliance was lower in post-Nissen compared with pre-Nissen (8.39 ± 1.11 mL/mm Hg vs 9.15 ± 0.81 mL/mm Hg, respectively; P < 0.001) (Fig. 1). The difference in gastric distensibility and volume variation between the pre- and post-Nissen measurements was statistically significant (92.79 ± 14.05 mL vs 62.44 ± 11.55 mL, respectively; P = 0.035). There was a moderately significant interaction between the pressure parameter (P) and time (pre-Nissen, post-Nissen), which indicates a difference in the relationship between P and volume (V) for pre-Nissen and post-Nissen (P = 0.0627). Specifically, the slope of the P versus V curve for the pre-Nissen subjects was 10.28 mL (ie, as P increased by 1 point, the pre-Nissen V increased by 10.28 mm Hg), and the slope of the P versus V curve for the post-Nissen subjects was 7.74 (ie, as P increased by 1 mm Hg, the post-Nissen V increased by 7.74 mL). The correlation between the P and V values of the pre-Nissen subjects was 0.69, and the correlation between the P and V values of the post-Nissen subjects was 0.73.
Solid-phase Gastric Emptying
Gastric emptying before Nissen fundoplication was within normal limits for this age group. The gastric emptying rates were similar for the pre- and post-Nissen measurements 2 hours after feeding (71 ± 18% vs 62 ± 24%; P = 0.398) (Table 2). The slopes of the gastric emptying curves were also similar: pre-Nissen, 0.426% per minute; post-Nissen, 0.371% per minute (Fig. 2).
Perceptions of Pain
Pre-Nissen patients reported no pain (score, 0.88 ± 1.31) at any distention pressure, whereas post-Nissen patients reported pain (score, 1.41 ± 0.80) at distention pressures of 7 to 11 mm Hg (P = 0.0096 by repeated measures analysis) (Fig. 3). Thus, the level of perceived pain upon distention was higher in post-Nissen than in pre-Nissen.
To elucidate the effects of fundoplication surgery on the motor and sensory functions of the stomach of pediatric patients with GERD, we assessed gastric compliance, gastric sensory function and gastric emptying before and after Nissen fundoplication. In this prospective study, we found significant changes in the sensory and motor functions of the stomach after fundoplication.
The reduction in gastric tone that follows feeding, which is known as gastric accommodation, allows the ingestion of solids or liquids without postprandial discomfort. Abnormalities in this normal response associated with postprandial symptoms of early satiety, fullness and distention have been reported in adult patients with functional dyspepsia (13) who have symptoms resembling those occurring after fundoplication. Increased wall tone in response to distension or meal ingestion may lead to stimulation of visceral afferents and heightened perception of gastric events. Gastric compliance is a measure of the viscoelasticity of the stomach wall, in that it reflects the ability of the stomach to expand in response to an imposed pressure. In this study, gastric compliance was reduced significantly after Nissen fundoplication surgery, with the stomach becoming more rigid (less compliant) after surgery. The MDP assessed after isobaric distention was significantly elevated after Nissen fundoplication surgery. This is in accordance with the observed reduction in gastric compliance postsurgery; the greater rigidity of the post-Nissen stomach, the larger applied pressure is required to produce stretching, that is, the MDP was higher. Our finding that the MDP is significantly higher in post-Nissen than in pre-Nissen differs from the reports of Vu et al. (14) and Lindeboom et al. (15) who found no differences in the MDP between pre- and post-Nissen subjects. However, in these previous studies, the pre- and post-Nissen measurements were performed on 2 different groups of adult subjects. Our subjects served as their own controls because the same group of pediatric patients was tested both pre- and post-Nissen. The difference between our result and the one reported by Vu et al. is possibly related to stomach size and age.
The subjects reported higher levels of pain after surgery in response to same gastric distentions. Although the increases in the pain scores were modest after surgery, the heightened perception of pain may be related to the decrease in gastric compliance. Loss of stomach viscoelasticity after Nissen fundoplication may translate into feelings of discomfort or pain upon distention, caused by food ingestion or as mimicked by the barostat balloon.
These abnormalities in gastric accommodation may also have resulted from significant injury to the vagus nerve during the fundoplication. Because of the limitations in performing a sham feeding in this population, we were not able to separate the cephalic phase of feeding from the gastric phase. Nevertheless, finding no significant changes in gastric emptying lessens the possibility of postfundoplication vagal injury
The effect of fundoplication on gastric emptying was previously investigated. Reports by Velasco et al. (16) and McCallum et al. (17) found patients with reflux disease to have delayed gastric emptying. Maddern et al. (6) and Vu et al. (8) reported the improvement of the delayed gastric emptying after Nissen fundoplication. On the contrary, in our study, we investigated pediatric patients with normal gastric emptying before surgery and who had no significant changes after the surgery. We showed that the surgery had no significant impact on gastric emptying of a meal that contained both solids and liquids. This apparent discrepancy may be partly caused by the age of the subjects used in the previous and present studies (adults and children, respectively) and the differences in the types of fundoplication performed. It might not be possible to accelerate normal gastric emptying because none of the children in the study had a significantly delayed gastric emptying before surgery.
In summary, Nissen fundoplication surgery in children with GERD caused a decrease in gastric compliance, which probably accounted for the increased postsurgical discomfort experienced by the subjects after gastric distention or in response to feeding. The post-Nissen loss of viscoelasticity may account for the post-Nissen increase in MDP. We speculate that the anatomic and functional changes brought about by the Nissen fundoplication are closely related to the symptoms of postoperative dyspepsia.
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