Infantile Hypertrophic Pyloric Stenosis (IHPS) is a common condition in neonates, occurring in approximately 2 to 3.5 per 1000 live births. Males are 4-6 times.
MSF Paediatric Days 2017 Poster N° 1617
MEDICAL TREATMENT WITH ATROPINE FOR INFANTILE HYPERTROPHIC PYLORIC STENOSIS WHEN SURGERY IS NOT AN OPTION: A CASE PRESENTATION AND LITERATURE DISCUSSION Valori, Ana1; Lafferty, Nadia2
1Paediatrician, MSF-OCBA; 2
Paediatric Advisor MSF-OCBA
BACKGROUND Infantile Hypertrophic Pyloric Stenosis (IHPS) is a common condition in neonates, occurring in approximately 2 to 3.5 per 1000 live births. Males are 4-6 times more commonly affected than females, and there is a higher incidence in preterm compared to term newborns. Surgical pyloromyotomy is proven to be both effective and simple, and is considered the gold-standard treatment of pyloric stenosis. However, in resource-limited settings where trained staff is scarce, surgical intervention is not always possible. Conservative management with atropine has been described as a useful alternative to surgery in various studies. We present a case report and brief discussion of the literature to explore the potential of this treatment in MSF fields. CASE STUDY A 7 week old male presented to a rural MSF-supported hospital in the Democratic Republic of Congo (DRC), with a 2 week history of projectile vomiting and weight loss (2kg at admission compared to 3kg at birth). IHPS was suspected and ultrasound images were compatible. Given the degree of dehydration, low weight and patient instability, IV rehydration was prioritised. Transfer was not considered appropriate in the patient’s current condition, due to the rural location and length of transfer. As there was no on-site capacity to carry out neonatal surgery or anaesthesia, alternative treatments were sought. IV atropine was commenced at 0.02mg/kg every 6 hours after a review of available evidence, as no MSF protocol was available. The prescription was switched after 48h to an infusion of 0.5mg atropine/24h added to maintenance fluids, following a case review and discussion among colleagues. After 12 days of irregular vomiting and poor monitoring, the baby developed gastrointestinal bleeding, mixed haemorrhagic/septic shock and subsequently died. DISCUSSION Atropine relaxes smooth muscle, including the pyloric musculature, through its anticholinergic effects, and has therefore been explored as an alternative to surgical pyloromyotomy. Several small studies and one larger metaanalysis have shown very good success rates (up to 91%) using oral and IV atropine for pyloric stenosis, with no serious side effects identified (Table 1). In all studies, initial doses of IV atropine ranged from 0.01 - 0.06 mg/kg/day,
given in 6-8 divided doses. Typically, total daily dose was increased by 0.01mg/kg/day (to a maximum of 0.1 mg/kg/day) until vomiting ceased or an adequate volume of milk feeds was tolerated. In all studies, IV atropine was followed by oral atropine at twice the effective IV dose for 2-4 weeks. In studies using oral atropine only, initial doses were higher, and treatment tended to be continued for longer. While oral atropine had slightly lower success rates than IV atropine, it has the advantage of posing fewer dosage errors, allowing home treatment and being much cheaper to administer. Atropine, whether oral or IV, was always given immediately before milk feeds and atropine infusion was not described in any of the articles. In the studies with ultrasound results, all showed regression or normalisation of the pylorus after completion of treatment and at follow-up. Most studies showed cessation of vomiting between 6-8 days after commencing atropine treatment. Projectile vomiting ≥5 times/day in the first 3 days of starting IV atropine was shown to be a negative predictive factor. Success of atropine treatment appears to be linked to careful dosing incrementation, timing of administration in relation to feeds, and continued administration for a limited time after cessation of vomiting. In our case, dosing was not incremented on a daily basis, and the use of an atropine infusion did not allow administration of atropine to be timed with feeds. In addition, the dose of IV atropine delivered by infusion (0.5mg/day = 0.25mg/kg) was significantly higher than the maximum IV dose described in the literature. The lack of protocol for the use of atropine as a treatment for pyloric stenosis may have contributed to the poor outcome in this case.
Table 1: Overview of studies using atropine as conservative treatment for pyloric stenosis, and main outcomes
Study
Atropine regimen
Success rate
Time to stop Ultrasound findings vomiting
Nagita et al, 1996
IV atropine 0.04mg/kg/d in 8 divided doses, increased daily by 0.01mg/kg/d, followed by 21/23 (91.3%) 5 days oral atropine at twice effective IV dose for 2 weeks Singh et al, 2004 Oral atropine 0.18mg/kg/d in 8 divided doses, increased daily by 25% 11/12 14-21 days (91.06%) Kawahara et al, 2005 IV atropine 0.01mg/kg 6 times a day, followed by 0.02mg/kg/d oral atropine 45/52 (87%) 7 days
Daily ultrasound during hospitalisation then every 2 months. Normalisation of pyloric muscle thickness in 4-12 months in all infants US follow-up at 3, 6, 9, 12 and 15 months. Normalisation of pylorus in all cases by 3-15 months after completion of treatment NA
Lukac et al, 2013
Oral atropine 0.05mg/kg/d in 8 divided doses, increased daily by 0.01mg/kg/d until vomiting ceased. Oral atropine continued for 6-8 weeks after discharge.
30/40 (75%)
6-8 days
US follow-up at 7, 14 and 21 days, and 6 weeks showed regression of pyloric muscle wall to allow passage of stomach content to duodenum
Koike et al, 2013
As Nagita et al, 1996
18/31 (58%)
7-8 days
NA
Fan et al, 2016
IV atropine 0.06mg/kg/d in 8 divided doses, increased daily by 0.01mg/kg/d. Oral atropine given at double effective IV dose for 3-4 weeks. IV atropine followed by oral atropine (various doses, retrospective analysis of nationwide hospital database) IV atropine 0.04-0.06mg/kg/day, increased by 0.01mg/kg/d until vomiting ceased, followed by oral atropine at twice the effective dose(6 articles)
23/26 (88.5%) 1-4 days
Oral atropine 0.05mg/kg/d, increased to max 0.1mg/kg/d (11 articles)
77/110 (70%)
Takeuchi et al, 2013 Wu et al, 2016 (meta-analysis)
142/180 (78.9%) 288/345 (85.5%)
NA
US at 6 months showed no significant difference between mean thickness of the pyloric muscle in atropine vs pyloromyotomy groups NA
NA
Pyloric muscle normalisation varied from 5 weeks to 15 months
CONCLUSION There is convincing evidence for the use of atropine as an alternative to pyloromyotomy in pyloric stenosis, when surgical treatment is not possible. Several studies have demonstrated good success rates with no serious adverse effects. However, close monitoring and careful dosing are essential, especially when using IV atropine, and may be limiting factors in rural MSF settings with low-qualified staff. Oral atropine may be the most realistic and feasible option in our settings and should be explored further. Specific MSF protocols for the use of atropine in pyloric stenosis may help to optimise the chances of success. REFERENCES 1. Nagita A, Yamaguchi J, Amemoto K, Yoden A, Yamazaki T, Mino M. Management and Ultrasonographic Appearance of Infantile Hypertrophic Pyloric Stenosis with Intravenous Atropine Sulfate. J Pediatr Gastroenterol Nutr. 1996; 23(2):172-177 2. Singh UK, Kumar R, Prasad R. Oral atropine sulfate for infantile hypertrophic pyloric stenosis. Indian Pediatr. 2005; 42(5):473 3. Kawahara H, Takama Y, Yoshida H, Nakai H, Okuyama H, Kubota A, Yoshimura N, Ida S, Okada A. Medical treatment of infantile hypertrophic pyloric stenosis: should we always slice the "olive"? J Pediatr Surg. 2005; 40(12):1848 4. Lukac M, Antunovic SS, Vujovic D, Pavicevic P, Jesic M, Krstajic T, Petronic I, Nikolic D. Is abandonment of nonoperative management of hypertrophic pyloric stenosis warranted? Eur J Pediatr Surg. 2013 Feb; 23(1):80-4 5. Mercer AE, Phillips R. Question 2: can a conservative approach to the treatment of hypertrophic pyloric stenosis with atropine be considered a real alternative to surgical pyloromyotomy? Arch Dis Child. 2013 Jun; 98(6):474-477 6. Wu SF, Lin HY, Huang FK, Chen AC, Su BH, Li CI, Lin HC. Efficacy of Medical Treatment for Infantile Hypertrophic Pyloric Stenosis: A Meta-analysis. Pediatr Neonatol. 2016; 57(6):515 7. Koike Y, Uchida K, Nakazawa M, Inoue M, Kusunoki M, Tsukamoto Y. Predictive factors of negative outcome in initial atropine therapy for infantile hypertrophic pyloric stenosis. Pediatrics International. 2013; 55:619–623 8. Fan J, Shi Y, Cheng M, Zhu X, Wang D. Treating idiopathic hypertrophic pyloric stenosis with sequential therapy: A clinical study. Journal of Paediatrics and Child Health. 2016; 52: 734–738 9. Takeuchi M, Yasunaga H, Horiguchi H, Hashimoto H, Matsuda S. Pyloromyotomy versus i.v. atropine therapy for the treatment of infantile pyloric stenosis: Nationwide hospital discharge database analysis. Pediatrics International. 2013; 55:488–491 10. Jobson M, Hall N. Contemporary management of pyloric stenosis. Seminars in Pediatric Surgery. 2016; 25: 219-224
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