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Temporary percutaneous and permanent gastric electrical stimulation in children younger than 3 years with chronic vomiting
Journal of Pediatric Surgery (2011) 46, 655–661
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Temporary percutaneous and permanent gastric electrical stimulation in children younger than 3 years with chronic vomiting Anders Elfvin a,⁎, Gunnar Göthberg b , Hans Lönroth c , Robert Saalman a , Hasse Abrahamsson d a
Department of Pediatrics, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, 416 85 Gothenburg, Sweden b Department of Pediatric Surgery, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, 416 85 Gothenburg, Sweden c Department of Surgery, Sahlgrenska University Hospital, 416 85 Gothenburg, Sweden d Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden Received 3 June 2010; revised 28 September 2010; accepted 31 October 2010
Key words: Gastric electrical stimulation; Gastroparesis; Pediatric; Vomiting
Abstract Background: The aim was to investigate whether young children with drug-refractory nausea and vomiting can be treated with gastric electrical stimulation (GES) in a similar way as adults and to evaluate whether temporary percutaneous gastric electrical stimulation (TPGES) can be used in the pediatric population to select the patients who are responders to GES treatment. We report the clinical results in 3 children between 2 and 3 years of age. To the best of our knowledge, these are the youngest patients treated with GES. Methods: Three patients younger than 3 years with intractable vomiting underwent TPGES. Custommade leads were percutaneously implanted in the gastric wall under gastroscopic guidance. Symptoms were recorded daily during the TPGES stimulation time (12-40 days). Responders were offered permanent GES treatment. Results: There were no technical problems. All 3 patients were responders to TPGES. They are now treated with surgically implanted permanent GES and reported greater than 50% vomiting reduction at last visit. Conclusion: Children younger than 3 years can be treated with GES in a similar way as adolescents and adults. Temporary percutaneous GES is a safe, feasible technique even in small children, with the possibility to perform the test over several weeks to select responders to GES treatment. © 2011 Elsevier Inc. All rights reserved.
⁎ Corresponding author. Tel.: +46 31 343 40 00. E-mail address: [email protected] (A. Elfvin). 0022-3468/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2010.10.028
Gastric electrical stimulation (GES) is an established treatment of nausea and vomiting owing to drug-refractory diabetic and idiopathic gastroparesis in adults [1-4]. Positive effect of high-frequency, low-energy GES has also been
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shown for postsurgical drug-refractory gastroparesis [5,6]. The accepted indication for GES is delayed gastric emptying. However, no study has actually shown that GES treatment improves gastric emptying [3]. Gastric electrical stimulation has in fact been proven to be effective in conditions with severe nausea and vomiting without gastroparesis [7,8]. We recently reported that GES is effective in reducing vomiting frequency in adults with chronic intestinal pseudoobstruction even in patients without gastroparesis [7]. To be able to select the responders to GES from the nonresponders in the group of patients with nonestablished indications for GES, several new techniques for temporary GES have been developed [3,9-11]. The technique described by Ayinala et al [9] uses oral leads implanted through the gastric mucosa. We have developed a minimally invasive gastroscopy-guided percutaneous technique for temporary GES that has the advantage of being less invasive and cheaper than the permanent surgical implantation technique [10,11]. The patients who respond to temporary stimulation can then be offered permanent GES. The new techniques of temporary stimulation increase the possibility to explore a potential benefit of GES with a simple temporary test in new patient groups with therapy-refractory symptoms. Among pediatric patients, a simple minimally invasive technique to select responders to GES would open new methods to help children with severe drug-refractory nausea and vomiting, with or without gastroparesis. Islam et al [12] have reported positive results of GES in children and adolescents. In their study, the patients' mean age was 14 years; and the youngest child was 8 years old. The aim of this study was to investigate whether very young children with drug-refractory nausea and vomiting can be treated with GES in a similar way as adults. A secondary aim was to evaluate whether temporary percutaneous GES can be used in the pediatric population to select the patients who are responders to GES treatment. Table 1
In the present study, we report the clinical result of temporary percutaneous gastric electrical stimulation (TPGES) and permanent GES in 3 children between 2 and 3 years old; and to the best of our knowledge, these are the youngest patients treated with GES to date.
1. Material and methods Approval to perform TPGES to test if pediatric patients with severe nausea and/or vomiting are responders to GES and candidates for chronic GES was obtained from the Ethics Committee, University of Gothenburg (Dnr 375-06).
1.1. Patients Entry criteria were children with severe nausea and vomiting interfering with daily life. The weekly vomiting frequency (WVF) in combination with the interference with daily life activities for the affected child was the strongest factors for inclusion. Patients were considered for GES if they had a WVF greater than 7 that had persisted for more than 1 year. Symptoms should be drug refractory and unresponsive to treatment with erythromycin or cisapride. Gastroparesis was not a mandatory criterion. Patients with and without gastroparesis could be included. Exclusion criteria were the findings of other treatable causes of vomiting such as elevated intracranial pressure. The first 3 pediatric patients treated with GES in Gothenburg are presented in this study. A summary of patient characteristics is shown in Table 1. 1.1.1. Patient 1 The first patient was a girl with cardiofaciocutaneous (CFC) syndrome. Her birth weight was 3.4 kg. In the
Patient characteristics
Patient
Sex
Age (y)
Cause
Gastroparesis
Diagnosis/other morbidity
Other
1
F
2
Malformation syndrome
No
CFC syndrome Hypertrophic left ventricle Pulmonary hypertension
2
M
2 4/12
Idiopathic/related to prematurity
Yes
Premature, 31 + 2 wk; SGA (BW, 1095 g) Neonatal IRDS Hypospadias Inguinal hernia Premature, 30 + 5 wk SGA (BW, 595 g) Neonatal BPD Hypospadias Undescended testis GER
Gastrostomy Central venous catheter Op gastropexy Op Nissen fundoplication Gastrostomy
3
M
2 11/12
Idiopathic/related to prematurity
No
Jejunal tube Twin Gastrostomy Op Nissen fundoplication Twin
BW indicates body weight; IRDS, infant respiratory distress syndrome; SGA, small for gestational age; BPD, broncho-pulmonal dysplasia.
GES in young children neonatal period, she presented with frequent vomiting. She was diagnosed as having gastric malrotation and underwent surgery with gastropexy, but vomiting persisted with a vomiting frequency of 10 to 30 times daily and extensive abdominal pain. Gastroesophageal reflux (GER) disease was suspected; and at the age of 6 months, a Nissen fundoplication was performed, with some effect on the volumes of vomit, but no effect on the vomiting frequency or the abdominal pain. She could hardly eat anything orally or via gastrostomy tube. She was treated with total parenteral nutrition via a central venous catheter. Result of scintigraphic examination for gastric emptying was normal. Small bowel contrast study revealed no anatomical abnormalities. Treatment with cisapride and erythromycin had no effect on the symptoms. At the referral hospital, treatment with promethazine, metoclopramide, and ondansetron had been tried without any significant effect. Related to her CFC syndrome, she also had cardiac disease with left ventricular hypertrophy and pulmonary hypertension that was treated with propranolol. As neurologic changes including hydrocephalus can be part of CFC syndrome, patient 1 had previously been evaluated for increased intracranial pressure as a possible cause of vomiting. That investigation included a computed tomographic scan and showed no signs of increased intracranial pressure. 1.1.2. Patient 2 The second patient, a twin boy, was born prematurely at 31 + 2 weeks' gestation. He was small for gestational age (SGA), with a birth weight of 1095 g. During the neonatal period, he had infant respiratory distress syndrome. He was diagnosed with a left inguinal hernia and penoscrotal hypospadias that required operative repair. During the neonatal period, he had frequent vomiting that persisted. At the age of 7 months, he received a gastric tube with no effect on the vomiting frequency. Scintigraphic examination showed delayed gastric emptying, that is, gastroparesis. Examination with 24-hour pH recording for GER showed Reflux Index in the upper channel of 1.6% and in the lower channel of 0.9%. At the age of 1 year, he received a transgastric jejunal tube for feeding. Treatment with metoclopramide, erythromycin, and cisapride had no effect on the symptoms. Patient 2 had no signs of other disease processes including of the central nervous system as a possible cause of vomiting. 1.1.3. Patient 3 The third patient, a twin boy, was born prematurely at 30 + 5 weeks' gestation. He was SGA, with a birth weigh of 595 g. The birth weight of his twin brother was 1690 g. He was diagnosed with a scrotal hypospadias and cryptorchidism that were surgically treated. He developed bronchopulmonary dysplasia requiring extra oxygen during his first months of life. He had frequent vomiting during the neonatal period; and at the age of 5 months, symptoms increased and the patient
657 refused oral feedings. Examination with scintigraphic gastric emptying and 24-hour pH studies showed GER. At the age of 1 year, a gastrostomy tube was inserted; and at the age of 1 8/12 years, a Nissen fundoplication was performed. After surgery, the frequency of vomiting decreased markedly; but he was still vomiting 1 to 4 times daily. Several scintigraphic examinations showed a normal gastric emptying rate. Small bowel contrast studies showed no anatomical abnormalities. Treatment with erythromycin and cisapride had no effect on the symptoms. He received nutrition mainly via the gastrostomy, with only small amounts of food orally. Patient 3 had no signs of disease including of the central nervous system as a possible cause of vomiting.
1.2. Gastric emptying test A standardized liquid scintigraphic emptying test using a complex liquid meal labeled with 99-technetium modified for children was used [13,14]. At the Department of Clinical Physiology at The Queen Silvia Children's Hospital in Gothenburg, the normal value for gastric emptying expressed as half emptying time was 60 minutes.
1.3. Temporary percutaneous GES 1.3.1. Implantation technique The patients underwent TPGES to test if they were candidates for permanent GES. The technique used for TPGES is described in detail elsewhere [10]. In adults, the implantation is performed using local anesthesia. In these children, lead implantation was performed under general anesthesia. Custom-made leads having an outer silicone layer and a diameter of 1.2 mm were used. The leads were inserted through a plastic cannula into the submucosal layer of the stomach. The tip of the lead is T-shaped with flexible wing-like tines and was capable of anchoring itself in the submucosa. Just proximal to the tines, the leads have a cylindrical electrode with length of 2.4 mm and diameter of 1.2 mm. The implantation of electrodes was performed under gastroscopic guidance. After transabdominal identification of the gastroscopy light, local anesthesia was administered; and abdominal skin incision was made. A plastic cannula with an inner needle was introduced through the abdominal wall into the gastric wall until the tip of the needle was tenting, but not passing through, the gastric mucosa. Saline was injected into the submucosal layer, thus creating a liquid-filled space between the mucosal and muscular layers. The lead was then inserted through the cannula into the submucosa. The 2 electrodes were placed in the wall at the border between corpus and antrum. Any mucosal perforation would have been detected via the gastroscopic guidance. The gastroscope was then withdrawn, and the leads were connected to the impulse generator (Enterra; Medtronic Inc, Minneapolis, MN). The impulse generator was fixed to
658 the skin using a bandage, and the electrode impedance measured. The distance between the 2 electrodes in the gastric wall was measured by a radiograph using an external metal piece on the abdominal skin as reference. At the end of the TPGES period, the leads were extracted by a smooth steady pulling motion, with the patient under a short general anesthetic. 1.3.2. Temporary percutaneous GES study design In adults, TPGES has been performed in a double-blind crossover fashion [11]. However, in these first 3 pediatric patients, taking their young age into consideration, the study was performed with open stimulation. The impulse generator was set in on mode during the whole TPGES period. 1.3.3. Stimulation technique The impulse pattern used was similar to that used in TPGES studies in adults [10,11]. The stimulation rate was 14 Hz during 0.1 second, with intervals of 5 seconds. Thus, each stimulus consisted of 2 discrete impulses; the pulse width was 330 microseconds, and the interpulse interval was 70 milliseconds. This resulted in a stimulation of 12 stimuli per minute. Stimulation was applied 24 h/d. The stimulation current was set based on measured impedance and appropriate adjustment of the stimulation voltage. Impedance in the range 300 to 900 Ω was considered appropriate for bipolar stimulation. In all 3 patients, stimulation started with low-milliampere TPGES, that is, in the range of 5.0 to 7 mA. If there was no clearcut response to low-milliampere stimulation, the settings were changed to a high-milliampere TPGES with stimulation in the range of 8 to 11 mA. The stimulation time was planned to be 12 to 14 days, with the possibility of extending stimulation time with an extra period to try high-milliampere TPGES if needed. Throughout the stimulation period, the patients were monitored for signs of infection and discomfort. 1.3.4. Monitored parameters The patients' families reported symptoms daily in a diary. Weekly vomiting frequency was recorded. If possible, with regard to the patients' young age, weekly nausea time (WNT), postprandial fullness, and abdominal pain were also assessed. The family also reported general signs of improvement such as changes in the child's daily activities and general condition. The basis for responder classification was improvement in WVF, as described below, in combination with signs of improvement of their general condition. 1.3.5. Responder criteria The criteria to be classified as a responder to TPGES were adopted from previous studies [2,11]. However, the patients' young age and difficulties in describing symptoms as nausea, bloating, and early satiety were taken into consideration. The main symptom recorded was vomiting, presented as WVF. The patient was considered a definite responder if the WVF
A. Elfvin et al. was reduced by at least 50% during stimulation vs baseline. A definite nonresponder was defined as WVF reduction less than 25%. [15]. Much attention was also paid to signs of improvement in their general condition during the TPGES period. Weekly nausea time could be recorded in 1 of the 3 patients.
1.4. Chronic GES 1.4.1. Surgical technique Laparoscopic placement of GES electrodes in adults is the recommended surgical technique. [7]. This approach can also be applied in children [12]. However, in this study, previous surgical interventions in combination with the patients' young age made open surgery the preferred surgical technique. A laparotomy was performed; and the electrodes were placed on the anterolateral surface of the stomach, anchored with 2 sutures at the proximal end and a plastic pad and a metal clip at the distal end of the lead. The leads were connected to the neurostimulator that was placed subcutaneously and anchored to the fascia with nonabsorbable sutures. 1.4.2. Stimulation technique Stimulation during chronic GES was performed using similar settings as described for TPGES. After recording of the impedance, the voltage was set to reach a current of 5 to 7 mA for low-milliampere GES. If no or only slight symptom improvement was recorded at follow-up, the current was increased to 8 to 11 mA. 1.4.3. Monitored parameters Vomiting (WVF) was recorded 2 weeks ahead of the permanent implantation for baseline recording. Daily diaries for 2 weeks were then recorded by the patients' family for the first 2 weeks after implantation and in relation to follow-up visits at 3, 6, 12, and 24 months. Follow-up is then planned to be at least once a year.
2. Results 2.1. Temporary percutaneous GES 2.1.1. Technical outcome of TPGES implantation The leads in all 3 patients were implanted under general anesthesia. This is in accordance with the routine of always performing gastroscopy for children under general anesthesia at our hospital. There were no technical problems in performing the implantation. As shown in Fig. 1, the electrodes were placed on the anterolateral region of the stomach. One of the patients (patient 1) had a cutaneous fungal infection under the bandage after about 10 days. The infection was treated with antifungal agents. At the end of the observation period, the leads were extracted without complications.
GES in young children
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Fig. 1 Temporary percutaneous GES. Percutaneous leads implanted to the stomach in a 2-year-old boy with chronic vomiting. Arrows indicate (1) electrodes in the gastric wall. (2) Most of the leads and the neurostimulator are taped to the abdominal skin. (3) Transgastric jejunal tube, not related to the TPGES.
2.1.2. Stimulation settings As shown in Table 2, the primary settings aimed to yield a current in the lower-milliampere range. Patient 1 responded promptly to treatment, and no changes were necessary. For the other 2 patients, the settings were changed to high-milliampere stimulation during the last part of the TPGES period. For patient 3, a current of 11 mA was used at the end of the period; and the observation period was extended.
Table 2 GES
2.1.3. Outcome of TPGES At the final evaluation, all 3 patients were considered responders. However, the response differed between the patients (Fig. 2). Patient 1 responded promptly to low– milliampere TPGES with an 85% decrease in vomiting from a baseline WVF of 126 to a WVF of 17 during stimulation. The TPGES had no effect on the abdominal pain in this patient. The patient's general condition was reported to improve during the observation period. Patient 2 started on a baseline WVF of 31 and reduced the WVF to 15 during stimulation. This is a decrease of more than 50% in WVF compared with baseline. The best response was seen with settings at a high-milliampere TPGES, as shown in Table 2, at the end of the period. Patient 3 had a baseline WVF of 21. The response to lowmilliampere TPGES in patient 3 was less conclusive. After increasing the current to 11 mA, the patient showed a decrease in WVF from 21 to 13. This is an improvement of only 38%, and the patient fulfilled neither the WVF frequency criteria for definite responders nor the McCallum criterion for nonresponders [15]. However, the improvement in WVF in combination with a very obvious change in general condition with a more active and happy child and less nausea motivated the decision to consider the patient a responder.
2.2. Permanent GES 2.2.1. Technical outcome of GES implantation All 3 patients underwent open surgery because of patient size and intraabdominal adhesions following previous surgery. There were no complications related to the operation. The impulse generator was placed subcutaneously in the lower left or right quadrant (Fig. 3). None of the patients experienced any complications related to the procedure. No discomfort or other complications related to the stimulator have been reported.
Stimulation settings during TPGES and permanent
At 6 mo of Patient Start of End of Time with Start of TPGES TPGES TPGES (d) permanent permanent GES GES 1
2
3
785 Ω 4V 5.0 mA 410 Ω 3V 7.3 mA 521 Ω 2.6 V 5 mA
720 Ω 12 4V 5.6 mA 390 Ω 12 3.5 V 9.0 mA 371 Ω 40 4.2 V 11 mA
375 Ω 1.9 V 5.1 mA 513 Ω 3.2 V 6.2 mA 608 Ω 4.2 V 6.9 mA
667 Ω 4.7 V 7.5 mA 484 Ω 3.9 V 8.1 mA 608 Ω 4.8 V 8 mA
Fig. 2 Effect of TPGES on vomiting. The WVF decreased in all 3 patients. In one patient, the decrease in vomiting was greater than 85%.
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2.2.2. Outcome of permanent GES As shown in Fig. 4, all 3 patients have been followed for at least 6 months. All 3 patients had a decrease in WVF of more than 50% at 6 months of follow-up. Patient 1 had a baseline WVF of 61 before starting the permanent GES. At 6 months of follow-up, patient 1 had a decrease in WVF to 22. Patient 2 had a decrease in WVF from a baseline of 19 to a WVF of 9 at 6 months of follow-up. In patient 3, there was a decrease from a baseline of 15 to a WVF of 7 at 6 months with permanent GES stimulation. Notable is the continuing decrease in WVF at 12 months of follow-up in patients 1 and 2, with a WVF of 14 and 2, respectively. In one of the patients, patient 1, with vomiting and severe abdominal pain, GES had a prompt effect on the vomiting frequency, but no effect on the pain. In this specific patient, the pain has been effectively treated with gabapentin.
3. Discussion
Several studies have shown that high-frequency GES has beneficial effects on symptoms in patients with diabetic or idiopathic gastroparesis [2-4,16,17]. However, in idiopathic gastroparesis, the nonresponder rate to permanent GES has been reported to be as high as 30% to 50% [18,19]. The effect of GES does not seem to correlate with improved gastric emptying [2-4,18]. It has been proposed that the antiemetic effect of GES may be mainly mediated by vagal afferent pathways [19-21]. A positive effect of GES in most patients with intractable nausea and vomiting without gastroparesis has been reported [7,8,11]. To select responders among patients with nonestablished indications for GES, the novel technique of temporary percutaneous stimulation was established in our group [7,10]. Gastric electrical stimulation is not yet an established method of treating nausea and vomiting in children. Currently, there is an increasing international interest in treating children and adolescents with GES [12,22]. As there are no established indications for GES in children, it is of great importance to find ways to select responders to the treatment. In this study, the new TPGES technique was used to select responders among children younger than 3 years. The present TPGES technique is similar to the first steps when placing a percutaneous endoscopic gastrostomy, which is a routine method even in small children. Because of the patients' young age, the study was performed as an open TPGES with the stimulator in on mode throughout the period. Weekly vomiting frequency was used to select responders. Other symptoms like nausea (WNT), bloating, and early satiety are more difficult to record in young children. Recording the child's general condition is a subjective report from the parents and might be affected by bias for the families' desire for a positive effect. In the future, it might therefore be recommended to perform a double-blinded TPGES even in small children. Further experience in this field is needed. The settings applied in this study for temporary and permanent GES were similar to those used in adults. One 70
Weekly vomiting frequency
Fig. 3 Permanent GES implanted to the stomach of a 2-year-old girl. Arrows indicate (1) electrodes in the gastric wall. (2) Neurostimulator placed subcutaneously.
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60 50 40
Patient 1 Patient 2
30
Patient 3
20 10 0
The present pilot study shows that children younger than 3 years with intractable nausea and vomiting can be treated successfully with GES. Furthermore, the study shows that TPGES can be used on small children to select responders to GES treatment.
Before GES
1 week
6 months
12 months
24 months
Fig. 4 Permanent GES. All 3 patients have shown a decrease in WVF of more than 50% during the first 6 months of permanent GES. In patients 1 and 2, the decrease in WVF seems to be even greater after 12 months with permanent GES.
GES in young children child responded to low-milliampere TPGES, whereas the other 2 needed high-milliampere stimulation for a full response. None of the patients showed any signs of discomfort related to the higher current. We conclude that high-milliampere stimulation with a current up to 11 mA is safe even in small children. In one patient, the TPGES period was extended to 40 days without any complications or discomfort. This indicates that TPGES can be safely used for several weeks even in children younger than 3 years to identify responders. For implantation of the permanent GES leads, laparoscopy is the recommended surgical technique [7,23]. In the present study, however, all patients had a gastrostomy; and open surgery was performed in all 3 cases. In selected cases, laparoscopy for lead implantation may well be the method of choice even in small children. The present study showed good agreement between the initial response to TPGES and the clinical effects obtained with permanent GES. The number of patients in this study is limited. However, the results thus far indicate that TPGES is a feasible method of selecting responders among children with intractable nausea and vomiting. Furthermore, this study showed positive results in children both with and without gastroparesis. Thus, GES seems to be effective in children with severe nausea and vomiting regardless of the presence of gastroparesis. As this pilot study has shown a positive response to GES, our group is now starting a larger double-blinded study to confirm and evaluate these results. The basis of the entry criteria will be children with severe therapy-refractory vomiting interfering with daily life activities. The present study of TPGES and permanent GES in children younger than 3 years has shown that very young children with drug-refractory nausea and vomiting can be treated with GES in a similar way as adolescents and adults. Furthermore, the study shows that TPGES is a safe, feasible technique even in small children, with the possibility of performing the test over several weeks, to identify responders to GES treatment.
Acknowledgment This study was supported by the Swedish Research Council (grant 13409), and by the Sahlgrenska Academy. The percutaneous lead electrodes were custom-made by Bakken Research Center BV, Maastricht, the Netherlands.
References [1] Lin Z, McElhinney C, Sarosiek I, et al. Chronic gastric electrical stimulation for gastroparesis reduces the use of prokinetic and/or antiemetic medications and the need for hospitalizations. Dig Dis Sci 2005;50(7):1328-34.
661 [2] Abell T, McCallum R, Hocking M, et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology 2003;125(2): 421-8. [3] Abell TL, Van Cutsem E, Abrahamsson H, et al. Gastric electrical stimulation in intractable symptomatic gastroparesis. Digestion 2002;66(4):204-12. [4] Lin Z, Forster J, Sarosiek I, et al. Treatment of diabetic gastroparesis by high-frequency gastric electrical stimulation. Diabetes Care 2004;27(5):1071-6. [5] McCallum R, Lin Z, Wetzel P, et al. Clinical response to gastric electrical stimulation in patients with postsurgical gastroparesis. Clin Gastroenterol Hepatol 2005;3(1):49-54. [6] Oubre B, Luo J, Al-Juburi A, et al. Pilot study on gastric electrical stimulation on surgery-associated gastroparesis: long-term outcome. South Med J 2005;98:693-7. [7] Andersson S, Lönroth H, Simrén M, et al. Gastric electrical stimulation for intractable vomiting in patients with chronic intestinal pseudoobstruction. Neurogastroenterol Motil 2006;18(9):823-30. [8] Gourcerol G, Gallas S, Mounien L, et al. Gastric electrical stimulation modulates hypothalamic corticotropin-releasing factor–producing neurons during post-operative ileus in rat. Neuroscience 2007;148 (3):775-81. [9] Ayinala S, Batista O, Goyal A, et al. Temporary gastric electrical stimulation with orally or PEG-placed electrodes in patients with drug refractory gastroparesis. Gastrointest Endosc 2005;61(3):455-61. [10] Elfvin A, Andersson S, Abrahamsson H, et al. Percutaneous implantation of gastric electrodes—a novel technique applied in animals and in patients. Neurogastroenterol Motil 2007;19(2):103-9. [11] Andersson S, Ringström G, Elfvin A, et al. Temporary percutaneous gastric electrical stimulation (GES). A novel technique tested in patients with non-established indications for GES. Digestion 2011;83: 3-12. [12] Islam S, Vick LR, Runnels MJ, et al. Gastric electrical stimulation for children with intractable nausea and gastroparesis. J Pediatr Surg 2008;43(3):437-42. [13] Grybäck P, Hermansson G, Lyrenäs E, et al. Nationwide standardisation and evaluation of scintigraphic gastric emptying: reference values and comparisons between subgroups in a multicentre trial. Eur J Nucl Med 2000;27(6):647-55. [14] Heyman S. Gastric emptying in children. J Nucl Med 1998;39(5):865-9. [15] McCallum RW, Dusing RW, Sarosiek I, et al. Mechanisms of symptomatic improvement after gastric electrical stimulation in gastroparetic patients. Neurogastroenterol Motil 2010;22(2):161-7. [16] Mason RJ, Lipham J, Eckerling G, et al. Gastric electrical stimulation: an alternative surgical therapy for patients with gastroparesis. Arch Surg 2005;140(9):841-6 discussion 847-8. [17] Anand C, Al-Juburi A, Familoni B, et al. Gastric electrical stimulation is safe and effective: a long-term study in patients with drug-refractory gastroparesis in three regional centers. Digestion 2007;75(2-3):83-9. [18] Lin Z, Sarosiek I, Forster J, et al. Predictors of symptom nonresponders to high-frequency gastric electrical stimulation for refractory gastroparesis. Gastroenterology 2006;130:A246. [19] Maranki JL, Lytes V, Meilahn JE, et al. Predictive factors for clinical improvement with Enterra gastric electric stimulation treatment for refractory gastroparesis. Dig Dis Sci 2008;53(8):2072-8 Epub 2007 Dec 14. [20] Forster J, Sarosiek I, Delcore R, et al. Gastric pacing is a new surgical treatment for gastroparesis. Am J Surg 2001;182(6):676-81. [21] Qin C, Sun Y, Chen JD, et al. Gastric electrical stimulation modulates neuronal activity in nucleus tractus solitarii in rats. Auton Neurosci 2005;119(1):1-8. [22] Hyman P, Schropp K, Sarosiek I, et al. Feasibility and safety of gastric electrical stimulation for a child with intractable visceral pain and gastroparesis. J Pediatr Gastroenterol Nutr 2009;49(5):635-8. [23] Lönroth H, Abrahamsson H. Laparoscopic and open placement of electronic implants for gastric electrical stimulation (GES): technique and results. Minim Invasive Ther Allied Technol 2004;13(5):336-9.
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Temporary percutaneous and permanent gastric electrical stimulation in children younger than 3 years with chronic vomiting Anders Elfvin a,⁎, Gunnar Göthberg b , Hans Lönroth c , Robert Saalman a , Hasse Abrahamsson d a
Department of Pediatrics, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, 416 85 Gothenburg, Sweden b Department of Pediatric Surgery, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, 416 85 Gothenburg, Sweden c Department of Surgery, Sahlgrenska University Hospital, 416 85 Gothenburg, Sweden d Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden Received 3 June 2010; revised 28 September 2010; accepted 31 October 2010
Key words: Gastric electrical stimulation; Gastroparesis; Pediatric; Vomiting
Abstract Background: The aim was to investigate whether young children with drug-refractory nausea and vomiting can be treated with gastric electrical stimulation (GES) in a similar way as adults and to evaluate whether temporary percutaneous gastric electrical stimulation (TPGES) can be used in the pediatric population to select the patients who are responders to GES treatment. We report the clinical results in 3 children between 2 and 3 years of age. To the best of our knowledge, these are the youngest patients treated with GES. Methods: Three patients younger than 3 years with intractable vomiting underwent TPGES. Custommade leads were percutaneously implanted in the gastric wall under gastroscopic guidance. Symptoms were recorded daily during the TPGES stimulation time (12-40 days). Responders were offered permanent GES treatment. Results: There were no technical problems. All 3 patients were responders to TPGES. They are now treated with surgically implanted permanent GES and reported greater than 50% vomiting reduction at last visit. Conclusion: Children younger than 3 years can be treated with GES in a similar way as adolescents and adults. Temporary percutaneous GES is a safe, feasible technique even in small children, with the possibility to perform the test over several weeks to select responders to GES treatment. © 2011 Elsevier Inc. All rights reserved.
⁎ Corresponding author. Tel.: +46 31 343 40 00. E-mail address: [email protected] (A. Elfvin). 0022-3468/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2010.10.028
Gastric electrical stimulation (GES) is an established treatment of nausea and vomiting owing to drug-refractory diabetic and idiopathic gastroparesis in adults [1-4]. Positive effect of high-frequency, low-energy GES has also been
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shown for postsurgical drug-refractory gastroparesis [5,6]. The accepted indication for GES is delayed gastric emptying. However, no study has actually shown that GES treatment improves gastric emptying [3]. Gastric electrical stimulation has in fact been proven to be effective in conditions with severe nausea and vomiting without gastroparesis [7,8]. We recently reported that GES is effective in reducing vomiting frequency in adults with chronic intestinal pseudoobstruction even in patients without gastroparesis [7]. To be able to select the responders to GES from the nonresponders in the group of patients with nonestablished indications for GES, several new techniques for temporary GES have been developed [3,9-11]. The technique described by Ayinala et al [9] uses oral leads implanted through the gastric mucosa. We have developed a minimally invasive gastroscopy-guided percutaneous technique for temporary GES that has the advantage of being less invasive and cheaper than the permanent surgical implantation technique [10,11]. The patients who respond to temporary stimulation can then be offered permanent GES. The new techniques of temporary stimulation increase the possibility to explore a potential benefit of GES with a simple temporary test in new patient groups with therapy-refractory symptoms. Among pediatric patients, a simple minimally invasive technique to select responders to GES would open new methods to help children with severe drug-refractory nausea and vomiting, with or without gastroparesis. Islam et al [12] have reported positive results of GES in children and adolescents. In their study, the patients' mean age was 14 years; and the youngest child was 8 years old. The aim of this study was to investigate whether very young children with drug-refractory nausea and vomiting can be treated with GES in a similar way as adults. A secondary aim was to evaluate whether temporary percutaneous GES can be used in the pediatric population to select the patients who are responders to GES treatment. Table 1
In the present study, we report the clinical result of temporary percutaneous gastric electrical stimulation (TPGES) and permanent GES in 3 children between 2 and 3 years old; and to the best of our knowledge, these are the youngest patients treated with GES to date.
1. Material and methods Approval to perform TPGES to test if pediatric patients with severe nausea and/or vomiting are responders to GES and candidates for chronic GES was obtained from the Ethics Committee, University of Gothenburg (Dnr 375-06).
1.1. Patients Entry criteria were children with severe nausea and vomiting interfering with daily life. The weekly vomiting frequency (WVF) in combination with the interference with daily life activities for the affected child was the strongest factors for inclusion. Patients were considered for GES if they had a WVF greater than 7 that had persisted for more than 1 year. Symptoms should be drug refractory and unresponsive to treatment with erythromycin or cisapride. Gastroparesis was not a mandatory criterion. Patients with and without gastroparesis could be included. Exclusion criteria were the findings of other treatable causes of vomiting such as elevated intracranial pressure. The first 3 pediatric patients treated with GES in Gothenburg are presented in this study. A summary of patient characteristics is shown in Table 1. 1.1.1. Patient 1 The first patient was a girl with cardiofaciocutaneous (CFC) syndrome. Her birth weight was 3.4 kg. In the
Patient characteristics
Patient
Sex
Age (y)
Cause
Gastroparesis
Diagnosis/other morbidity
Other
1
F
2
Malformation syndrome
No
CFC syndrome Hypertrophic left ventricle Pulmonary hypertension
2
M
2 4/12
Idiopathic/related to prematurity
Yes
Premature, 31 + 2 wk; SGA (BW, 1095 g) Neonatal IRDS Hypospadias Inguinal hernia Premature, 30 + 5 wk SGA (BW, 595 g) Neonatal BPD Hypospadias Undescended testis GER
Gastrostomy Central venous catheter Op gastropexy Op Nissen fundoplication Gastrostomy
3
M
2 11/12
Idiopathic/related to prematurity
No
Jejunal tube Twin Gastrostomy Op Nissen fundoplication Twin
BW indicates body weight; IRDS, infant respiratory distress syndrome; SGA, small for gestational age; BPD, broncho-pulmonal dysplasia.
GES in young children neonatal period, she presented with frequent vomiting. She was diagnosed as having gastric malrotation and underwent surgery with gastropexy, but vomiting persisted with a vomiting frequency of 10 to 30 times daily and extensive abdominal pain. Gastroesophageal reflux (GER) disease was suspected; and at the age of 6 months, a Nissen fundoplication was performed, with some effect on the volumes of vomit, but no effect on the vomiting frequency or the abdominal pain. She could hardly eat anything orally or via gastrostomy tube. She was treated with total parenteral nutrition via a central venous catheter. Result of scintigraphic examination for gastric emptying was normal. Small bowel contrast study revealed no anatomical abnormalities. Treatment with cisapride and erythromycin had no effect on the symptoms. At the referral hospital, treatment with promethazine, metoclopramide, and ondansetron had been tried without any significant effect. Related to her CFC syndrome, she also had cardiac disease with left ventricular hypertrophy and pulmonary hypertension that was treated with propranolol. As neurologic changes including hydrocephalus can be part of CFC syndrome, patient 1 had previously been evaluated for increased intracranial pressure as a possible cause of vomiting. That investigation included a computed tomographic scan and showed no signs of increased intracranial pressure. 1.1.2. Patient 2 The second patient, a twin boy, was born prematurely at 31 + 2 weeks' gestation. He was small for gestational age (SGA), with a birth weight of 1095 g. During the neonatal period, he had infant respiratory distress syndrome. He was diagnosed with a left inguinal hernia and penoscrotal hypospadias that required operative repair. During the neonatal period, he had frequent vomiting that persisted. At the age of 7 months, he received a gastric tube with no effect on the vomiting frequency. Scintigraphic examination showed delayed gastric emptying, that is, gastroparesis. Examination with 24-hour pH recording for GER showed Reflux Index in the upper channel of 1.6% and in the lower channel of 0.9%. At the age of 1 year, he received a transgastric jejunal tube for feeding. Treatment with metoclopramide, erythromycin, and cisapride had no effect on the symptoms. Patient 2 had no signs of other disease processes including of the central nervous system as a possible cause of vomiting. 1.1.3. Patient 3 The third patient, a twin boy, was born prematurely at 30 + 5 weeks' gestation. He was SGA, with a birth weigh of 595 g. The birth weight of his twin brother was 1690 g. He was diagnosed with a scrotal hypospadias and cryptorchidism that were surgically treated. He developed bronchopulmonary dysplasia requiring extra oxygen during his first months of life. He had frequent vomiting during the neonatal period; and at the age of 5 months, symptoms increased and the patient
657 refused oral feedings. Examination with scintigraphic gastric emptying and 24-hour pH studies showed GER. At the age of 1 year, a gastrostomy tube was inserted; and at the age of 1 8/12 years, a Nissen fundoplication was performed. After surgery, the frequency of vomiting decreased markedly; but he was still vomiting 1 to 4 times daily. Several scintigraphic examinations showed a normal gastric emptying rate. Small bowel contrast studies showed no anatomical abnormalities. Treatment with erythromycin and cisapride had no effect on the symptoms. He received nutrition mainly via the gastrostomy, with only small amounts of food orally. Patient 3 had no signs of disease including of the central nervous system as a possible cause of vomiting.
1.2. Gastric emptying test A standardized liquid scintigraphic emptying test using a complex liquid meal labeled with 99-technetium modified for children was used [13,14]. At the Department of Clinical Physiology at The Queen Silvia Children's Hospital in Gothenburg, the normal value for gastric emptying expressed as half emptying time was 60 minutes.
1.3. Temporary percutaneous GES 1.3.1. Implantation technique The patients underwent TPGES to test if they were candidates for permanent GES. The technique used for TPGES is described in detail elsewhere [10]. In adults, the implantation is performed using local anesthesia. In these children, lead implantation was performed under general anesthesia. Custom-made leads having an outer silicone layer and a diameter of 1.2 mm were used. The leads were inserted through a plastic cannula into the submucosal layer of the stomach. The tip of the lead is T-shaped with flexible wing-like tines and was capable of anchoring itself in the submucosa. Just proximal to the tines, the leads have a cylindrical electrode with length of 2.4 mm and diameter of 1.2 mm. The implantation of electrodes was performed under gastroscopic guidance. After transabdominal identification of the gastroscopy light, local anesthesia was administered; and abdominal skin incision was made. A plastic cannula with an inner needle was introduced through the abdominal wall into the gastric wall until the tip of the needle was tenting, but not passing through, the gastric mucosa. Saline was injected into the submucosal layer, thus creating a liquid-filled space between the mucosal and muscular layers. The lead was then inserted through the cannula into the submucosa. The 2 electrodes were placed in the wall at the border between corpus and antrum. Any mucosal perforation would have been detected via the gastroscopic guidance. The gastroscope was then withdrawn, and the leads were connected to the impulse generator (Enterra; Medtronic Inc, Minneapolis, MN). The impulse generator was fixed to
658 the skin using a bandage, and the electrode impedance measured. The distance between the 2 electrodes in the gastric wall was measured by a radiograph using an external metal piece on the abdominal skin as reference. At the end of the TPGES period, the leads were extracted by a smooth steady pulling motion, with the patient under a short general anesthetic. 1.3.2. Temporary percutaneous GES study design In adults, TPGES has been performed in a double-blind crossover fashion [11]. However, in these first 3 pediatric patients, taking their young age into consideration, the study was performed with open stimulation. The impulse generator was set in on mode during the whole TPGES period. 1.3.3. Stimulation technique The impulse pattern used was similar to that used in TPGES studies in adults [10,11]. The stimulation rate was 14 Hz during 0.1 second, with intervals of 5 seconds. Thus, each stimulus consisted of 2 discrete impulses; the pulse width was 330 microseconds, and the interpulse interval was 70 milliseconds. This resulted in a stimulation of 12 stimuli per minute. Stimulation was applied 24 h/d. The stimulation current was set based on measured impedance and appropriate adjustment of the stimulation voltage. Impedance in the range 300 to 900 Ω was considered appropriate for bipolar stimulation. In all 3 patients, stimulation started with low-milliampere TPGES, that is, in the range of 5.0 to 7 mA. If there was no clearcut response to low-milliampere stimulation, the settings were changed to a high-milliampere TPGES with stimulation in the range of 8 to 11 mA. The stimulation time was planned to be 12 to 14 days, with the possibility of extending stimulation time with an extra period to try high-milliampere TPGES if needed. Throughout the stimulation period, the patients were monitored for signs of infection and discomfort. 1.3.4. Monitored parameters The patients' families reported symptoms daily in a diary. Weekly vomiting frequency was recorded. If possible, with regard to the patients' young age, weekly nausea time (WNT), postprandial fullness, and abdominal pain were also assessed. The family also reported general signs of improvement such as changes in the child's daily activities and general condition. The basis for responder classification was improvement in WVF, as described below, in combination with signs of improvement of their general condition. 1.3.5. Responder criteria The criteria to be classified as a responder to TPGES were adopted from previous studies [2,11]. However, the patients' young age and difficulties in describing symptoms as nausea, bloating, and early satiety were taken into consideration. The main symptom recorded was vomiting, presented as WVF. The patient was considered a definite responder if the WVF
A. Elfvin et al. was reduced by at least 50% during stimulation vs baseline. A definite nonresponder was defined as WVF reduction less than 25%. [15]. Much attention was also paid to signs of improvement in their general condition during the TPGES period. Weekly nausea time could be recorded in 1 of the 3 patients.
1.4. Chronic GES 1.4.1. Surgical technique Laparoscopic placement of GES electrodes in adults is the recommended surgical technique. [7]. This approach can also be applied in children [12]. However, in this study, previous surgical interventions in combination with the patients' young age made open surgery the preferred surgical technique. A laparotomy was performed; and the electrodes were placed on the anterolateral surface of the stomach, anchored with 2 sutures at the proximal end and a plastic pad and a metal clip at the distal end of the lead. The leads were connected to the neurostimulator that was placed subcutaneously and anchored to the fascia with nonabsorbable sutures. 1.4.2. Stimulation technique Stimulation during chronic GES was performed using similar settings as described for TPGES. After recording of the impedance, the voltage was set to reach a current of 5 to 7 mA for low-milliampere GES. If no or only slight symptom improvement was recorded at follow-up, the current was increased to 8 to 11 mA. 1.4.3. Monitored parameters Vomiting (WVF) was recorded 2 weeks ahead of the permanent implantation for baseline recording. Daily diaries for 2 weeks were then recorded by the patients' family for the first 2 weeks after implantation and in relation to follow-up visits at 3, 6, 12, and 24 months. Follow-up is then planned to be at least once a year.
2. Results 2.1. Temporary percutaneous GES 2.1.1. Technical outcome of TPGES implantation The leads in all 3 patients were implanted under general anesthesia. This is in accordance with the routine of always performing gastroscopy for children under general anesthesia at our hospital. There were no technical problems in performing the implantation. As shown in Fig. 1, the electrodes were placed on the anterolateral region of the stomach. One of the patients (patient 1) had a cutaneous fungal infection under the bandage after about 10 days. The infection was treated with antifungal agents. At the end of the observation period, the leads were extracted without complications.
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Fig. 1 Temporary percutaneous GES. Percutaneous leads implanted to the stomach in a 2-year-old boy with chronic vomiting. Arrows indicate (1) electrodes in the gastric wall. (2) Most of the leads and the neurostimulator are taped to the abdominal skin. (3) Transgastric jejunal tube, not related to the TPGES.
2.1.2. Stimulation settings As shown in Table 2, the primary settings aimed to yield a current in the lower-milliampere range. Patient 1 responded promptly to treatment, and no changes were necessary. For the other 2 patients, the settings were changed to high-milliampere stimulation during the last part of the TPGES period. For patient 3, a current of 11 mA was used at the end of the period; and the observation period was extended.
Table 2 GES
2.1.3. Outcome of TPGES At the final evaluation, all 3 patients were considered responders. However, the response differed between the patients (Fig. 2). Patient 1 responded promptly to low– milliampere TPGES with an 85% decrease in vomiting from a baseline WVF of 126 to a WVF of 17 during stimulation. The TPGES had no effect on the abdominal pain in this patient. The patient's general condition was reported to improve during the observation period. Patient 2 started on a baseline WVF of 31 and reduced the WVF to 15 during stimulation. This is a decrease of more than 50% in WVF compared with baseline. The best response was seen with settings at a high-milliampere TPGES, as shown in Table 2, at the end of the period. Patient 3 had a baseline WVF of 21. The response to lowmilliampere TPGES in patient 3 was less conclusive. After increasing the current to 11 mA, the patient showed a decrease in WVF from 21 to 13. This is an improvement of only 38%, and the patient fulfilled neither the WVF frequency criteria for definite responders nor the McCallum criterion for nonresponders [15]. However, the improvement in WVF in combination with a very obvious change in general condition with a more active and happy child and less nausea motivated the decision to consider the patient a responder.
2.2. Permanent GES 2.2.1. Technical outcome of GES implantation All 3 patients underwent open surgery because of patient size and intraabdominal adhesions following previous surgery. There were no complications related to the operation. The impulse generator was placed subcutaneously in the lower left or right quadrant (Fig. 3). None of the patients experienced any complications related to the procedure. No discomfort or other complications related to the stimulator have been reported.
Stimulation settings during TPGES and permanent
At 6 mo of Patient Start of End of Time with Start of TPGES TPGES TPGES (d) permanent permanent GES GES 1
2
3
785 Ω 4V 5.0 mA 410 Ω 3V 7.3 mA 521 Ω 2.6 V 5 mA
720 Ω 12 4V 5.6 mA 390 Ω 12 3.5 V 9.0 mA 371 Ω 40 4.2 V 11 mA
375 Ω 1.9 V 5.1 mA 513 Ω 3.2 V 6.2 mA 608 Ω 4.2 V 6.9 mA
667 Ω 4.7 V 7.5 mA 484 Ω 3.9 V 8.1 mA 608 Ω 4.8 V 8 mA
Fig. 2 Effect of TPGES on vomiting. The WVF decreased in all 3 patients. In one patient, the decrease in vomiting was greater than 85%.
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2.2.2. Outcome of permanent GES As shown in Fig. 4, all 3 patients have been followed for at least 6 months. All 3 patients had a decrease in WVF of more than 50% at 6 months of follow-up. Patient 1 had a baseline WVF of 61 before starting the permanent GES. At 6 months of follow-up, patient 1 had a decrease in WVF to 22. Patient 2 had a decrease in WVF from a baseline of 19 to a WVF of 9 at 6 months of follow-up. In patient 3, there was a decrease from a baseline of 15 to a WVF of 7 at 6 months with permanent GES stimulation. Notable is the continuing decrease in WVF at 12 months of follow-up in patients 1 and 2, with a WVF of 14 and 2, respectively. In one of the patients, patient 1, with vomiting and severe abdominal pain, GES had a prompt effect on the vomiting frequency, but no effect on the pain. In this specific patient, the pain has been effectively treated with gabapentin.
3. Discussion
Several studies have shown that high-frequency GES has beneficial effects on symptoms in patients with diabetic or idiopathic gastroparesis [2-4,16,17]. However, in idiopathic gastroparesis, the nonresponder rate to permanent GES has been reported to be as high as 30% to 50% [18,19]. The effect of GES does not seem to correlate with improved gastric emptying [2-4,18]. It has been proposed that the antiemetic effect of GES may be mainly mediated by vagal afferent pathways [19-21]. A positive effect of GES in most patients with intractable nausea and vomiting without gastroparesis has been reported [7,8,11]. To select responders among patients with nonestablished indications for GES, the novel technique of temporary percutaneous stimulation was established in our group [7,10]. Gastric electrical stimulation is not yet an established method of treating nausea and vomiting in children. Currently, there is an increasing international interest in treating children and adolescents with GES [12,22]. As there are no established indications for GES in children, it is of great importance to find ways to select responders to the treatment. In this study, the new TPGES technique was used to select responders among children younger than 3 years. The present TPGES technique is similar to the first steps when placing a percutaneous endoscopic gastrostomy, which is a routine method even in small children. Because of the patients' young age, the study was performed as an open TPGES with the stimulator in on mode throughout the period. Weekly vomiting frequency was used to select responders. Other symptoms like nausea (WNT), bloating, and early satiety are more difficult to record in young children. Recording the child's general condition is a subjective report from the parents and might be affected by bias for the families' desire for a positive effect. In the future, it might therefore be recommended to perform a double-blinded TPGES even in small children. Further experience in this field is needed. The settings applied in this study for temporary and permanent GES were similar to those used in adults. One 70
Weekly vomiting frequency
Fig. 3 Permanent GES implanted to the stomach of a 2-year-old girl. Arrows indicate (1) electrodes in the gastric wall. (2) Neurostimulator placed subcutaneously.
A. Elfvin et al.
60 50 40
Patient 1 Patient 2
30
Patient 3
20 10 0
The present pilot study shows that children younger than 3 years with intractable nausea and vomiting can be treated successfully with GES. Furthermore, the study shows that TPGES can be used on small children to select responders to GES treatment.
Before GES
1 week
6 months
12 months
24 months
Fig. 4 Permanent GES. All 3 patients have shown a decrease in WVF of more than 50% during the first 6 months of permanent GES. In patients 1 and 2, the decrease in WVF seems to be even greater after 12 months with permanent GES.
GES in young children child responded to low-milliampere TPGES, whereas the other 2 needed high-milliampere stimulation for a full response. None of the patients showed any signs of discomfort related to the higher current. We conclude that high-milliampere stimulation with a current up to 11 mA is safe even in small children. In one patient, the TPGES period was extended to 40 days without any complications or discomfort. This indicates that TPGES can be safely used for several weeks even in children younger than 3 years to identify responders. For implantation of the permanent GES leads, laparoscopy is the recommended surgical technique [7,23]. In the present study, however, all patients had a gastrostomy; and open surgery was performed in all 3 cases. In selected cases, laparoscopy for lead implantation may well be the method of choice even in small children. The present study showed good agreement between the initial response to TPGES and the clinical effects obtained with permanent GES. The number of patients in this study is limited. However, the results thus far indicate that TPGES is a feasible method of selecting responders among children with intractable nausea and vomiting. Furthermore, this study showed positive results in children both with and without gastroparesis. Thus, GES seems to be effective in children with severe nausea and vomiting regardless of the presence of gastroparesis. As this pilot study has shown a positive response to GES, our group is now starting a larger double-blinded study to confirm and evaluate these results. The basis of the entry criteria will be children with severe therapy-refractory vomiting interfering with daily life activities. The present study of TPGES and permanent GES in children younger than 3 years has shown that very young children with drug-refractory nausea and vomiting can be treated with GES in a similar way as adolescents and adults. Furthermore, the study shows that TPGES is a safe, feasible technique even in small children, with the possibility of performing the test over several weeks, to identify responders to GES treatment.
Acknowledgment This study was supported by the Swedish Research Council (grant 13409), and by the Sahlgrenska Academy. The percutaneous lead electrodes were custom-made by Bakken Research Center BV, Maastricht, the Netherlands.
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661 [2] Abell T, McCallum R, Hocking M, et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology 2003;125(2): 421-8. [3] Abell TL, Van Cutsem E, Abrahamsson H, et al. Gastric electrical stimulation in intractable symptomatic gastroparesis. Digestion 2002;66(4):204-12. [4] Lin Z, Forster J, Sarosiek I, et al. Treatment of diabetic gastroparesis by high-frequency gastric electrical stimulation. Diabetes Care 2004;27(5):1071-6. [5] McCallum R, Lin Z, Wetzel P, et al. Clinical response to gastric electrical stimulation in patients with postsurgical gastroparesis. Clin Gastroenterol Hepatol 2005;3(1):49-54. [6] Oubre B, Luo J, Al-Juburi A, et al. Pilot study on gastric electrical stimulation on surgery-associated gastroparesis: long-term outcome. South Med J 2005;98:693-7. [7] Andersson S, Lönroth H, Simrén M, et al. Gastric electrical stimulation for intractable vomiting in patients with chronic intestinal pseudoobstruction. Neurogastroenterol Motil 2006;18(9):823-30. [8] Gourcerol G, Gallas S, Mounien L, et al. Gastric electrical stimulation modulates hypothalamic corticotropin-releasing factor–producing neurons during post-operative ileus in rat. Neuroscience 2007;148 (3):775-81. [9] Ayinala S, Batista O, Goyal A, et al. Temporary gastric electrical stimulation with orally or PEG-placed electrodes in patients with drug refractory gastroparesis. Gastrointest Endosc 2005;61(3):455-61. [10] Elfvin A, Andersson S, Abrahamsson H, et al. Percutaneous implantation of gastric electrodes—a novel technique applied in animals and in patients. Neurogastroenterol Motil 2007;19(2):103-9. [11] Andersson S, Ringström G, Elfvin A, et al. Temporary percutaneous gastric electrical stimulation (GES). A novel technique tested in patients with non-established indications for GES. Digestion 2011;83: 3-12. [12] Islam S, Vick LR, Runnels MJ, et al. Gastric electrical stimulation for children with intractable nausea and gastroparesis. J Pediatr Surg 2008;43(3):437-42. [13] Grybäck P, Hermansson G, Lyrenäs E, et al. Nationwide standardisation and evaluation of scintigraphic gastric emptying: reference values and comparisons between subgroups in a multicentre trial. Eur J Nucl Med 2000;27(6):647-55. [14] Heyman S. Gastric emptying in children. J Nucl Med 1998;39(5):865-9. [15] McCallum RW, Dusing RW, Sarosiek I, et al. Mechanisms of symptomatic improvement after gastric electrical stimulation in gastroparetic patients. Neurogastroenterol Motil 2010;22(2):161-7. [16] Mason RJ, Lipham J, Eckerling G, et al. Gastric electrical stimulation: an alternative surgical therapy for patients with gastroparesis. Arch Surg 2005;140(9):841-6 discussion 847-8. [17] Anand C, Al-Juburi A, Familoni B, et al. Gastric electrical stimulation is safe and effective: a long-term study in patients with drug-refractory gastroparesis in three regional centers. Digestion 2007;75(2-3):83-9. [18] Lin Z, Sarosiek I, Forster J, et al. Predictors of symptom nonresponders to high-frequency gastric electrical stimulation for refractory gastroparesis. Gastroenterology 2006;130:A246. [19] Maranki JL, Lytes V, Meilahn JE, et al. Predictive factors for clinical improvement with Enterra gastric electric stimulation treatment for refractory gastroparesis. Dig Dis Sci 2008;53(8):2072-8 Epub 2007 Dec 14. [20] Forster J, Sarosiek I, Delcore R, et al. Gastric pacing is a new surgical treatment for gastroparesis. Am J Surg 2001;182(6):676-81. [21] Qin C, Sun Y, Chen JD, et al. Gastric electrical stimulation modulates neuronal activity in nucleus tractus solitarii in rats. Auton Neurosci 2005;119(1):1-8. [22] Hyman P, Schropp K, Sarosiek I, et al. Feasibility and safety of gastric electrical stimulation for a child with intractable visceral pain and gastroparesis. J Pediatr Gastroenterol Nutr 2009;49(5):635-8. [23] Lönroth H, Abrahamsson H. Laparoscopic and open placement of electronic implants for gastric electrical stimulation (GES): technique and results. Minim Invasive Ther Allied Technol 2004;13(5):336-9.