Is there any benefit with pantoprazole treatment in infantile hypertrophic pyloric stenosis?

CONTEXT: Previous studies demonstrated faster correction of metabolic derangement associated with hypertrophic pyloric stenosis with pre-operative intravenous (IV) histamine-2 receptor antagonists. AIMS: We investigated if similar outcomes are achieved with IV pantoprazole, a proton-pump inhibitor (PPI), including the subgroup of delayed presenters in the South African setting. SETTINGS AND DESIGN: A 5-year retrospective record review (January 2014-December 2018) compared the rate of metabolic correction in patients with hypertrophic pyloric stenosis at two tertiary centres. SUBJECTS AND METHODS: One centre routinely administers IV pantoprazole (1 mg/kg daily) preoperatively (PPI group) and the other does not (non-PPI group). Fluid administration, chloride supplementation and post-operative emesis were evaluated. STATISTICAL ANALYSIS: Spearman's rank correlation coefficient was used to calculate statistical significance for discrete dependent variables. Continuous variables were compared between the groups using the Student t-test. Fisher's exact contingency tables were used to classify categorical data and to assess the significance of outcome between two treatment options. P < 0.05 was considered statistically significant. RESULTS: Forty-two patients received IV pantoprazole and 24 did not. The mean time of metabolic correction was 8 h shorter in the PPI group (P = 0.067). Total pre-operative chloride administration correlated to the rate of metabolic correction in both cohorts (P < 0.0001). Profound hypochloraemia (chloride <85 mmol/l) was corrected 23 h faster in the PPI group (P < 0.004). Post-operative emesis was noted: 0.45 episodes/patient in the PPI group and 0.75 episodes/patient in the non-PPI group (P = 0.01). CONCLUSIONS: Pre-operative IV pantoprazole administration showed a faster correction of metabolic derangements, and in profound hypochloraemia, the correction occurred substantially faster in the PPI group. Post-operative emesis was significantly less frequent in the PPI group.

The Effect of Botulinum Toxin in Experimental Hypertrophic Pyloric Stenosis.

Purpose: Infantile hypertrophic pyloric stenosis is the most common cause of gastric outlet obstruction in the first month of life. Botulinum toxin (BT) is a neurotoxin produced by clostridium botulinum, which causes paralysis in skeletal muscles. We aimed to evaluate the effectiveness of BT in the experimental pyloric stenosis model. Methods: The study protocol was approved by the Selcuk University Medical Faculty Ethics Committee (2017/20). We performed an experimental study using 32 Wistar-Albino newborn rats. Rats were divided randomly into four groups with six rats in both control (C), and L-nitro-arginine methyl ester hydrochloride group, and 10 rats in each sham (S), and BT group. 100 mg/kg per day L-NAME was applied to all groups intraperitoneally for 14 days from birth except control group. 0.2 mL saline and 20 U/kg BT was injected by surgery to S and BT groups, respectively, at 21 days from birth. After 35 days all rats were sacrificed and biopsies were performed from pyloric muscle for histopathological examination. The results were evaluated with the "one-way ANOVA" test. Results: Total and circular muscle thickness of the groups were compared. The total muscle thickness of the L-NAME group was significantly higher than the control group (P = .031). Comparing the circular muscle thickness of botox group (BTG) with control group (CG) and L-NAME GROUP (LNG), muscle thickness was significantly smaller (P < .001, P < .001). The total muscle thickness of BTG was significantly different between LNG (P < .001). Conclusions: Hypertrophy of pylor in an experimental model was reduced by BT injection in this study. We think that Botox injection through endoscopic or interventional radiological methods may be an alternative method for surgery.

The Association Between Opioid Use and Outcomes in Infants Undergoing Pyloromyotomy.

PURPOSE: The purpose of this study was to describe the frequency and variation of opioid use across hospitals in infants undergoing pyloromyotomy and to determine the impact of opioid use on postoperative outcomes. METHODS: A retrospective cohort study (2005-2015) was conducted by using the Pediatric Health Information System (PHIS) database, including infants (aged <6 months) with pyloric stenosis who underwent pyloromyotomy. Infants with significant comorbidities were excluded. Opioid use was classified as a patient receiving at least 1 opioid medication during his or her hospital stay and categorized as preoperative, day of surgery, or postoperative (≥1 day after surgery). Outcomes included prolonged hospital length of stay (LOS; ≥3 days) and readmission within 30 days. FINDINGS: Overall, 25,724 infants who underwent pyloromyotomy were analyzed. Opioids were administered to 6865 (26.7%) infants, with 1385 (5.4%) receiving opioids postoperatively. In 2015, there was significant variation in frequency of opioid use by hospital, with 0%-81% of infants within an individual hospital receiving opioids (P < 0.001). Infants only receiving opioids on the day of surgery exhibited decreased odds of prolonged hospital LOS (odds ratio [OR], 0.85; 95% CI, 0.78-0.92). Infants who received an opioid on both the day of surgery and postoperatively exhibited increased odds of a prolonged hospital LOS (OR, 1.71; 95% CI, 1.33-2.20). Thirty-day readmission was not associated with opioid use (OR, 1.03; 95% CI, 0.93-1.14). IMPLICATIONS: There is national variability in opioid use for infants undergoing pyloromyotomy, and postoperative opioid use is associated with prolonged hospital stay. Nonopioid analgesic protocols may warrant future investigation.

Hypertrophic pyloric stenosis following persistent pulmonary hypertension of the newborn: a case report and literature review.

BACKGROUND: Although persistent pulmonary hypertension of the newborn (PPHN) and infantile hypertrophic pyloric stenosis (HPS) are both well-known diseases that occur in early infancy, PPHN complicated by HPS is rare. As nitric oxide (NO) is an important mediator of biological functions, on both the vascular endothelium and smooth muscle cells, the decreased production of NO might play a role in the pathogenesis of both PPHN and HPS. We present the case of a neonate who developed HPS following PPHN, including a detailed review on research published to date, and we discuss the pathogenesis of PPHN and HPS. CASE PRESENTATION: A female neonate born at 38 weeks of gestation, weighing 3140 g, developed PPHN due to meconium aspiration syndrome. Intensive treatment with high frequency oscillations and inhaled NO were initiated, and sildenafil and bosentan were added. She gradually recovered. At 15 days of age, the patient developed recurrent vomiting after feeding and the diagnosis of HPS was made. Intravenous atropine therapy was started at 20 days of age, but the efficacy was clinically unsatisfactory. The coadministration with transdermal nitroglycerin improved the symptoms, and oral feeding was successfully re-introduced. CONCLUSIONS: Our patient recovered from both PPHN and HPS using NO-related medications. A decrease in NO synthesis is likely to be a common pathway for PPHN and HPS.

Atropine Treatment for Hypertrophic Pyloric Stenosis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Several authors have reported the use of atropine as an alternative treatment to pyloromyotomy in infants with hypertrophic pyloric stenosis (HPS). Our aims were to review the efficacy of atropine in treating HPS and to compare atropine therapy versus pyloromyotomy. MATERIALS AND METHODS: Using a defined search strategy (PubMed, MEDLINE, OVID, Embase, Cochrane databases), two investigators independently identified studies reporting the use of atropine for HPS. Case reports and opinion articles were excluded. Outcome measures included success rate, side effects, and length of hospital stay. Maneuvers were compared using Fisher's exact test, and meta-analysis was conducted using RevMan 5.3. Data are expressed as mean ± standard deviation. RESULTS: Systematic review: of 2,524 abstracts screened, 51 full-text articles were analyzed. There were no prospective or randomized studies. Twelve articles (508 infants) reported HPS resolution using atropine in 402 (79.1%) patients. Atropine side effects were documented in 38/251 (15.1%) infants and included tachycardia, increased transaminases, and flushed skin. Meta-analysis: five studies compared atropine treatment (293 infants) with pyloromyotomy (537 infants). Pyloromyotomy had higher success rate (100%) than atropine (80.8%; p < 0.01) and shorter hospital stay (5.6 ± 2.3 vs. 10.3 ± 3.8 days, respectively; p < 0.0001). CONCLUSION: Comparative but nonrandomized studies indicate that atropine is less effective than pyloromyotomy to treat infants with HPS. Currently, there is no evidence-based literature to support atropine treatment in these infants. To our knowledge, atropine should be reserved for patients unfit for general anesthesia or surgery.

Treating idiopathic hypertrophic pyloric stenosis with sequential therapy: A clinical study.

AIM: The aim of this study was to explore the efficacy and safety of treating idiopathic hypertrophic pyloric stenosis with sequential therapy (ST). METHODS: From January 2010 to June 2013, 49 children with idiopathic hypertrophic pyloric stenosis were divided into two groups to accept either atropine ST (ST group, n = 26) or laparoscopic surgery (operation group, n = 23). The remission rate of vomiting, complications, hospital stay and medical expenditure were compared between the two groups. The body weight and the thickness of the pyloric muscle at 6 months after the treatments were also compared. RESULTS: The remission rate of vomiting was lower in the ST group (88.5%; 23/26) than in the operation group (100%, 23/23). The difference in the incidence rate of complications, body weight and pyloric muscle thickness was not statistically significant between the two groups. However, the hospital stay was significantly longer, while the medical expenditure was significantly lower in the ST group than in the operation group. CONCLUSIONS: Atropine ST is safe, effective and cost-effective as compared with operation; however, the efficacy of ST is lower than operation.

[Recurrent pyloric stenosis in a 7-year-old child with chronic granulomatous disease]. / Sténoses pyloriques récidivantes chez un enfant de 7ans atteint de granulomatose septique chronique.

Hypertrophic pyloric stenosis is a common affection in infants aged 3-8 weeks and typically does not affect older children. We report a case of pyloric stenosis that occurred recurrently at the ages of 3 and 7 years in a boy with X-linked chronic granulomatous disease. We emphasize the inflammatory origin of such stenosis, whose progression was favorable thanks exclusively to drug treatment with corticosteroids. We note that chronic granulomatous disease can affect the entire digestive tract, similar to inflammatory bowel disease in children.

Is abandonment of nonoperative management of hypertrophic pyloric stenosis warranted?

AIM: Evaluation of the effectiveness of oral atropine versus surgical therapy for hypertrophic pyloric stenosis (HPS). METHODOLOGY: A total of 66 consecutive patients with HPS were treated at the University Children's Hospital between January 2006 and December 2011. The diagnosis was initially based on medical history and confirmed by ultrasonography (US). The patients were divided into two groups according to the treatment preferred by their parents. The conservatively treated group, consisting of 33 boys and 7 girls, mean age 22.25 days, was given water-soluble atropine sulfate therapy at an initial dose of 0.05 mg/kg/day divided into 8 single doses, and administered after stomach decompression, 20 minutes prior to feeding. If vomiting persisted, the daily dose was progressively increased up to 0.18 mg/kg. If vomiting did not stop and full oral feeding was not reestablished in a week, surgery was done. The second group of 26 patients, mean age 20.86 days, underwent an operative procedure, Ramstedt extramucosal pyloromyotomy after the initial resuscitation. US evaluation was performed on days 7, 14, and 21. The outcome of the treatment was tested by Yates modification of the χ2 test. RESULTS: In the group of patients treated with atropine sulfate, 10 (25%) failed to respond to therapy, therefore, 8 boys and 2 girls underwent surgical treatment between the fifth and seventh day following institution of therapy. The remaining patients who received atropine sulfate (75%) were discharged when vomiting ceased, between the sixth and eighth day. They continued to take oral medication for 4 to 6 weeks, and were followed up by an ultrasound examination. The operated patients were discharged between the third and fifth day after surgery. There was a significant statistical difference between the groups regarding the outcome at a significance level of p < 0.05 (Yates χ2 = 5.839), with no complications regardless of the treatment option. However, at the significance level of p < 0.01 (Yates χ2 = 7.661), these methods demonstrate a difference in favor of surgical treatment. CONCLUSION: Further investigation of oral, intravenous or combined atropine sulfate treatment may clarify its position as an alternative to pyloromyotomy.

Conservative treatment of infantile hypertrophic pyloric stenosis with intravenous atropine sulfate does not replace pyloromyotomy.

Pyloromyotomy as described by Weber and Ramstedt has been the standard therapy for infantile hypertrophic pyloric stenosis since the 1960's and conservative therapy has been abandoned. The objective of this study was to test the effectiveness of systemic atropine applied intravenously for 7 days as a conservative therapeutic strategy and as an alternative to primary operation. Forty-two consecutive term infants with infantile hypertrophic pyloric stenosis were enrolled in the study over a period of 5 years. After confirmation of the diagnosis they all received intravenous atropine at a dose of 0.04 mg/(kg day) and increased by 0.01 mg/(kg day) up to 0.12 mg/(kg day), given as 6-8 single doses per/day. Nine pairs of parents requested that their child should be operated before completing the 7 days of medical therapy. Surgery was necessary in 8 of the remaining 33 infants (24,.2%) who did not improve after 7 days of conservative treatment. Successful treatment with i.v. atropine sulfate was achieved only in 25/33 term infants at an average maximal dose of 0.11 mg/(kg day), without any major side effects. Intravenous atropine sulfate has been considered as a potential alternative therapeutic strategy in the treatment of infantile hypertrophic pyloric stenosis. Clinical improvement however was often not seen before the 6th or 7th day of intravenous treatment. A success rate for the conservative approach of only 75% at day 7 in our study does not favour atropine therapy, in view of success rates above 95% with surgical repair.

Medical treatment of infantile hypertrophic pyloric stenosis: should we always slice the "olive"?

BACKGROUND/PURPOSE: Laparoscopic pyloromyotomy has recently gained wide acceptance as the optimum treatment of infantile hypertrophic pyloric stenosis (IHPS). However, medical treatment may be superior to laparoscopic surgery in invasiveness. The efficacy of our regimen of intravenous atropine therapy for IHPS was assessed in comparison with surgical treatment. METHODS: Medical treatment was initially chosen for 52 (61%) of 85 infants with IHPS at our institute between 1996 and 2004. Atropine was given intravenously at 0.01 mg/kg 6 times a day before feeding. When vomiting ceased and the infants were able to ingest 150 mL/kg per day of formula after stepwise increases in the feeding volume, they were given 0.02 mg/kg atropine 6 times a day orally, and the dose was decreased stepwise. RESULTS: Of the 52 patients, 45 (87%) ceased projectile vomiting with treatment using intravenous (median, 7 days) and subsequent oral (median, 44 days) atropine administration. The median hospital stay was 13 days (6-36), and no significant complications were encountered during atropine therapy. The remaining 7 patients required surgery. Of 40 who underwent surgery, 4 had wound infections and 1 with hemophilia had postoperative hemorrhagic shock. The patients who underwent successful atropine therapy had body weights comparable with those who underwent surgery at the age of 1 year. CONCLUSIONS: The high success rate of intravenous atropine therapy for IHPS suggests that this therapy is an effective alternative to pyloromyotomy if the length of the hospital stay and the necessity of continuing oral atropine medication are accepted.

[Conservative treatment of hypertrophic pyloric stenosis in children]. / Konservativno lecenje hipertroficne stenoze pilorusa kod dece.

INTRODUCTION: Hypertrophy of the pylorus causing obstruction of the gastric outlet, or infantile hypertrophic pyloric stenosis (IHPS), is the most common indication for abdominal surgery in infancy. The incidence of the condition is 3-4 per 1000 live births, and male infants are affected more often than females, in 4:1 ratio. Vomiting, as the first symptom, most often occurs between the third and fourth week after birth, rarely after second month, but there have been few reports of vomiting as late as 5 months. Etiology of IHPS is still controversial. Two theories have been quoted most: absence of non-adrenergic and non-cholinergic nerve fibers which are mediators of smooth muscle contraction, and absence of nitric oxide inhibitory innervation of pyloric smooth-muscle resulting in unopposed contraction of the sphincter in response to muscarinic stimulation. Atropine sulfate is known to inhibit acetylcholine competitively in neuroreceptors, acting peripherally as a competitive inhibitor of the muscarinic effects of acetylcholine, leading to decreased gastrointestinal peristalsis. This action is believed to be important in IHPS cases. AIM: The aim of this paper is to provide further information on potential role of atropine in the management of patients with IHPS. METHODS: From April 2000 to October 2002, 22 patients (16 boys and 6 girls), aged 21 days to 3 months, with IHPS were treated by oral administration of atropine sulfate in our institution. Diagnosis of IHPS was based on US examination in all cases. A nasogastric tube was inserted and left in situ. Medical treatment involved initial correction of fluid and electrolyte imbalance combined with oral administration of atropine sulfate. Atropin was given in the form of aqueous solution in initial dose of 0.05 mg/kg/d. The total daily dose was divided into 8 equal doses. Each dose was formulated to be given in a volume of 1 ml. Before the administration of each dose of atropine, stomach was decompressed by suction via nasogastric tube. The infant was placed on the right side with the head on the cot elevated 20 degrees to 30 degrees for 15 to 30 minutes after each atropine dose. Oral feeding with 10 ml of 10% glucose was then attempted. If feeding was tolerated, the same dose of atropine was administered 3 hours later, followed by a trial of 20 ml of 10% glucose. If tolerated, 10 ml of conventional formula was then tried after atropine administration 3 hours later. The volume of formula was then increased 10 ml per feed until full feeding (120 ml/kg/d) was tolerated. Dribbling (2-3 times per day) was ignored. If vomiting occurred, the same dose of atropine, volume and type of feed, were tried again 3 hours later, and if still not tolerated, atropine was increased by 1 microg/kg/dose without increasing the volume of feed. This approach was repeated until oral feeding was tolerated at least twice, and only then the volume of oral feed was increased. During night shift (between 11 p.m. and 5 a.m.), atropine concentration and amount of oral feed were not increased. If vomiting recurred, the volume of oral feed was decreased to the last tolerated volume and maintained until the following day. Oral atropine was increased until predetermined maximum oral dose (0.1 mg/kg/d) was reached. If oral administration of atropine was ineffective, a decision to perform pyloromyotomy was made no later than 7 days after commencement of oral atropine. RESULTS: Atropine had effect (vomiting frequency less than twice per day) on average 3.29 days (range 1-7 days) from commencement. Oral atropine was tolerated very well, and was effective in 18 cases. Four cases were referred to pyloromyotomy, on day 4 (2 patients), day 5 (1 patient) and on day 6 (1 patient) of atropine treatment. Therapy was continued until US showed normalization of pyloric muscle thickness, passage of food through wide pyloric channel and until patients started gaining weight. Average duration of therapy was 24.05 days (11-39 days). Neither of patients from our group was treated with intravenous atropine sulfate. DISCUSSION: Although intravenous atropine is more effective (as shown by Nagita et al), there is an increased incidence of side effects such as flushing and tachycardia. Oral atropine has been used successfully by other teams without side effects, and there were no side effects or complications related to the use of atropine in this study. Prospective, randomized study comparing outcomes of medical versus surgical management of IHPS in our hospital has been currently in progress and will provide further information on potential role of atropine in the management of patients with IHPS. CONCLUSION: We believe it is unlikely that oral or intravenous atropine will ever replace surgery for IHPS, but it may be a good alternative to pyloromyotomy, particularly in children with major concurrent primary disease, or when parents are not enthusiastic about surgery in so young children.