Conservative Management with Atropine Therapy for Infantile Hypertrophic Pyloric Stenosis

INTRODUCTION

Infantile hypertrophic pyloric stenosis (IHPS) is a common infantile disorder characterized by enlarged pyloric musculature resulting in obstruction of gastric outlet¹ . IHPS occurs in approximately 1–4 per 1000 live births, although rates and trends vary markedly from region to region² .

The exact aetiology and pathophysiology are unknown, but the reason for clinical presentation is hypertrophy of the circular muscle layer of the pylorus, which causes gastric outlet obstruction. The diagnosis is usually clinical; it is based on a suggestive history and confirmed by palpation of the hypertrophied pylorus, or ‘olive’, which has a positive predictive value of 99%³ .

IHPS is usually diagnosed by abdominal ultrasound, on which it is illustrated by increased thickness, length and diameter of pyloric muscle^3,4.

Fredet-Ramstedt pyloromyotomy has been regarded as the optimal treatment for infantile hypertrophic pyloric stenosis (IHPS), although surgical complications have been reported^5,6.

Medical treatment with atropine has been proposed as an alternative to surgical treatment. Atropine sulphate is a cholinergic drug with strong antimuscarinic effects, which temporarily suppresses spastic contractions of pyloric muscle in pyloric stenosis.7,8 The clusters of tonic and phasic pyloric contractions characteristic of infantile hypertrophic pyloric stenosis are transiently abolished by an intravenous atropine injection of 0.01 mg/kg.8,9 However, researchers in India also reported a success rate of 96% with medical treatment10. The objective of this study was to study success rate, efficacy and complications of atropine therapy.

MATERIAL AND METHOD:

This prospective study was conducted in KBN Teaching and General Hospital, over a period of 4 years from March 2016 to February 2020. 25 infants presented with diagnosis of Infantile Hypertrophic pyloric stenosis and subsequently managed conservatively with atropine were included in the study.

Infants which were managed with surgical intervention or with cardiac anomalies or with multiple anomalies were excluded from the study.

The diagnosis of IHPS was made clinically by the typical clinical presentation of non-bilious vomiting, gastric peristalsis or palpable pyloric mass and was confirmed with ultrasound. In abdominal ultrasound IHPS is characterized by increased pyloric muscle thickness ≥3 mm and pyloric channel length 14 mm or greater. Dehydration was defined based on sunken fontanelle, dry mucous membranes, poor skin turgor and lethargy.

All infants first resuscitated with 1/2 Normal saline and KCl, underwent electrolyte correction Atropine was initially administered intravenously in a dose of 0.06 mg/kg/day in eight divided doses in a day, increased by 0.15 mg/kg/day till vomiting ceased and remained so for a period of 48 hours at a stretch and Ultrasonography showed a transit time (of gastric contents through pyloric canal) of less than 1 minute.

During atropine infusion, the heart rate was continuously monitored by electrocardiography. Oral feeding was started at a volume of 10 ml/3 hourly 8 times a day. The volume was increased day by day until patients tolerated 150 ml/kg/day (418 J/kg/day), unless vomiting occurred more than twice a day. When patients were able to tolerate the full volume without vomiting more than twice a day, Intravenous atropine was then substituted by oral atropine which was given at an initial dose of 0.05 mg/kg/d and increased to a maximum dose of 0.1 mg/kg/d for 3 weeks. Ultrasonographic evaluation of pyloric muscle thickness and length was done at the commencement of IV treatment, after completion of oral treatment and at 3,6,9,12 and 15 months follows.

Intravenous atropine treatment was considered unsuccessful if patients failed to tolerate half of the full volume within a week or the full volume within two weeks. They were discharged from the hospital when vomiting was controlled with oral atropine. When patients were free of vomiting and showed steady weight gain, atropine was decreased in three steps (0.12 mg/kg/day, 0.06 mg/kg/day, 0.03 mg/kg/day). If patients vomited more than twice a day for three days after discontinuation of atropine treatment, oral administration was restarted.

Clinical presentation, electrolytes abnormalities on admission, ultrasound finding, outcomes of treatment, length of hospital stay and mortality were recorded in the study.

Statistical analysis was done using SPSS Sofware, Version 18.0.

RESULTS

Total 25 IHPS infants were admitted and managed with atropine therapy during the period of study. Out of 25 infants, 22 (88%) were males and 03(12%) females with a male to female ratio of 7.3:1. Mean birth weight of infants was 3.1±1.4 kg. 20 (80%) infants were first-born children.

There were 07 (28 %) infants who started vomiting very early during the 1st week of life, while the majority of patients, 15 (60 %) became symptomatic within 1 month of age. Only 03 (12 %) patients became symptomatic after 1 month of age. The mean age at presentation was 5.2 ± 1.2 weeks with a range of 8 days to 12 weeks.

Progressive non-bilious vomiting was the most frequent symptom and it was described in all (100 %) patients, Visible peristalsis seen in 20 (80%) infants and A palpable mass was found in 14(56%) of infants [Table 1].

Metabolic alkalosis seen in 18(72%) infants. Electrolyte abnormality seen in 20 (80%) infants in which Hyponatremia seen in 18(72%), Hypokalemia seen in 16 (64%), Hypochloremia seen in 16 (64%) infants [Table2].

On Ultra sound mean thickness [Figure 1] of pyloric circular muscle was 5.1 ±1 (range 3-8mm) and length of pyloric muscle [Figure 2] was ranging from 15 to 38 mm with mean 20.1 ±3. No patient required any other diagnostic investigation for confirmation of diagnosis.

Of the 25 patients, 20 (80%) became free from projectile vomiting during atropine treatment and treated successfully with atropine therapy. Five cases continued to vomit at least twice daily even after 12days of IV treatment and ultimately opted out for pyloromyotomy after 12 days of intravenous atropine. Full feeding was achieved at 5+/- 4.3 days.

I.V. atropine was used for 6.3 +/- 4.1 days, and the oral form was used for 25 +/- 5 days. The total number of days of atropine sulfate treatment was 32.4 +/- 6.58 days.

Complications included transiently elevated heart rates (180-200 beats/min) in 03(12%) patients and facial flushing after the first dose of IV atropine in 01 (4%) patient. All the 25 medically treated children made uneventful recovery during oral therapy and ultrasonographic evidence of normalization of pylorus was observed in all these children 3-15 months after completion of oral therapy.

Mean duration of hospital stay was 10.36 ± 3.59 days (range of 8 –16 days). There was no mortality in the study population.

DISCUSSION:

Surgical treatment is superior to medical treatment with regard to response and shorter hospital stay. However, it has complications like perforation of duodenal mucosa, wound infection, wound dehiscence, gastroenteritis, post operative pyrexia and the risk of anesthesia^5,6.

Conservative treatment with atropine has been an option for IHPS treatment, using a step up dosage technique with intravenous atropine administration and was associated with a successful short term outcome with minimal risk^11,12.

In our study the males were more affected than females with a male to female ratio of 7.3:1 which is comparable with other studies^13,14,15.

Our study showed higher incidence of IHPS in the first born infants (80%) which was in agreement with most literatures15,16. In our study non-bilious vomiting was most predominant symptom seen in all infants (100%). The classic presentation of an olive mass in the epigastric region on palpation was seen in 56% of the cases which was comparable with other studies^14,15.

In patients with IHPS, serum electrolytes should be measured immediately when the patient arrives in hospital. If vomiting has been ongoing for several days, serum electrolytes are frequently deranged. The nature of derangement is a spectrum, ranging from mild to severe hyponatraemia, hypochloraemia, hypokalaemia, and metabolic alkalosis^16,17. In the current study, serum electrolytes results revealed hypokalaemia (64 %), hyponatraemia (72 %) and hypochloraemia (64 %) which is an expected occurrence in untreated cases. When this derangement occurs they should be corrected.

In most of cases vomiting was controlled long before resolution of hypertrophy and the relevant antimuscarinic effect of atropine is control of spasm produced by acetylcholine, the basic defect could be none or underproduction of endogenous neuro-transmitters which antagonize the action of acetylcholine, e.g., Nitrous Oxide(No.) and Vasoactive Intestinal Polypeptide (VIP). Normalization of endogenous production of these neurotransmitters during the course of atropine therapy could be the reason behind non-relapse in many of these patients. However, variation in the effective dose of atropine could be due to variations in the endogenous production of neurotransmitters, subjective differences in the sensitivity of muscarinic receptors and drug delivery and clearance system^18,19.

Although there has been some concern about sideeffects of atropine no serious complications have been reported in our study except tachycardia in 12% and facial flushing in 3 % which was similar with other studies¹¹.

In patients with IHPS treated with atropine, Nagita et al¹¹ reported that the time to normalisation of pyloric muscle thickness ranged from four to 12 months. Yamataka et al¹² reported that the normalisation of pyloric muscle thickness was not significantly different between patients undergoing pyloromyotomy (3.8±2.0 months) and those treated with atropine (3.4±2.3 months)¹². The present study indicated that pyloric muscle thickness was significantly less and there was normalisation of pyloric canal length on completion of oral atropine treatment.

Other concerns with atropine treatment are the length of hospital stay and the necessity to continue oral atropine medication after being discharged home, which requires good compliance by the parents. Kawahara and co-workers reported that the duration of hospital stay for patients treated surgically was significantly shorter than that of the atropine group (5 days [4–29] vs 13 [6–36] days)²⁰. We found in our study the hospital stay was 10.36 ± 3.59 days (range of 8 –16 days).

The success rate of conservative medical treatment was 80% in our study which was comparable with other studies reported by Kawahara et al20 (87%), Singh et al10(96%) and Kasuko et al21(96%).

The value of intravenous atropine as a treatment for IHPS remains controversial²². It has not gained wide acceptance mainly because it requires a prolonged hospital stay and treatment at home. Although pyloromyotomy has been regarded as the optimum treatment of IHPS, the actual and potential consequences of surgery cannot be ignored^5,6 .

CONCLUSION:

Conservative Management With Atropine Therapy For Infantile Hypertrophic Pyloric Stenosis proved to be an effective and safe option for treatment and it may be a good alternative to pyloromyotomy.

Source of Financial Support: Nil

Conflict of Interest: No