Successful use of neostigmine for resistant gastroparesis following distal gastrectomy: A case report

Abstract

Introduction and importance

Although short acting acetyl cholinesterase inhibitors are used in colonic or small bowel pseudo-obstruction, their use in post-surgical gastroparesis is not clear. We demonstrate the successful use of neostigmine in a patient with resistant gastroparesis following distal gastrectomy.

Case presentation

A 73-year-old male presented with features of gastric outflow obstruction 3 weeks following a distal gastrectomy. Prior to 3 weeks, he underwent an uneventful open distal gastrectomy for an incidentally detected low grade gastrointestinal stromal tumour (GIST) of the gastric antrum. An omega-loop isoperistaltic, 2-layer, posterior, retrocolic gastrojenunostomy was performed with a jejuno-jejunostomy. Abdominal ultrasonography was negative for intra-abdominal collections. Gastrograffin study and endoscopy ruled out an obstruction. A trial of prokinetics was unsuccessful with persistent nasogastric tube drain. Intravenous neostigmine was commenced with immediate symptomatic relief, reduction of abdominal distension and bowel evacuation without any cardiac adverse effects. At 6 months follow up, the patient was tolerating normal diet with no recurrence of symptoms.

Clinical discussion

The management of post-surgical gastroparesis is challenging. Although various prokinetics are described for gastric motility disorders, the studies among post-gastrectomy patients with gastroparesis are limited. In our patient, the successful administration of neostigmine avoided the morbidity due to revision surgery.

Conclusion

The use of neostigmine infusion was safe and effective for post-surgical gastroparesis after distal gastrectomy in our patient. To date, there are no trials investigating the place of neostigmine for resistant gastroparesis after gastric surgery and future studies are warranted prior to routine use in clinical practice.

Highlights

• •The management of resistant post-surgical gastroparesis is challenging.
• •Neostigmine was safe and effective in relieving gastroparesis in our patient.
• •Further clinical research is needed before routine use in clinical practice.

1. Introduction

Acetyl cholinesterase inhibitors are used in colonic or small bowel pseudo-obstruction due to their prokinetic effect with enhancement of small bowel and colonic motility [1]. Neostigmine is a short-acting acetyl cholinesterase inhibitor that is commonly used in colonic pseudo-obstruction [1]. It has also been shown to increase gastric motility and emptying of liquids in critically ill patients with delayed gastric emptying [1]. However, the use of neostigmine was also associated with irregular enhancement of gastric and duodenal contractility [2]^, [3]. The use of short acting acetyl cholinesterase inhibitors for gastroparesis in the post-surgical setting is controversial and not utilised in clinical practice.

This case demonstrates the successful use of neostigmine in a patient with resistant gastroparesis following distal gastrectomy avoiding the morbidity due to an additional surgical revision procedure. The work has been reported based on the SCARE 2020 criteria [4].

2. Presentation of case

A 73-year-old male presented with persistent vomiting 3 weeks following a distal gastrectomy. Prior to 3 weeks, he underwent an uneventful open distal gastrectomy following nutritional optimization for an asymptomatic, incidentally detected low grade gastrointestinal stromal tumour (GIST) with a maximum diameter of 4.5 cm arising from the posterior wall of the gastric antrum. During the surgery, an omega-loop isoperistaltic, 2-layer, posterior, retrocolic gastrojenunostomy was performed with a jejuno-jejunostomy. He was discharged on day 6 on normal diet after an uncomplicated post-operative period.

He had persistent hiccups and bilious vomiting few hours after meals for 2 days prior to the current admission. There was no associated colicky abdominal pain. He was on oral medications for long standing diabetes mellitus and hypertension. He was also on tamsulosin after transurethral resection of prostate for benign prostatic obstruction. The patient was a non-smoker and had no family history of relevance. His allergy and psychosocial histories were unremarkable.

On admission, he was dehydrated with marginal urine output. His other vital parameters were normal. His blood pressure was 125/84 mm Hg and pulse rate was 90 beats per minute. His abdomen was mildly distended but non-tender with audible bowel sounds.

Initial biochemistry and haematology revealed hypokalaemia (3.4 mmol/L), hyponatraemia (132 mmol/L) and increased C-reactive protein (121 mg/L). The rest of the blood investigations including serum albumin were unremarkable. A plain abdominal radiograph demonstrated absent small bowel gas and the large bowel contained gas and faecal shadows (Fig. 1). Abdominal ultrasonography revealed a grossly distended stomach with echogenic material suggestive of food particles. There were no intra-abdominal collections. The plain radiograph and the abdominal ultrasonography also showed a non-obstructing calculus in the left pelvi-ureteric junction. Gastrograffin contrast study was performed which revealed no contrast in small bowel up to 12 h following ingestion (Fig. 2). However, a plain radiograph taken 24 h after the study revealed contrast in the colon (Fig. 3). A gastroscopy revealed an oedematous anastomotic site with a patent anastomosis (Fig. 4). The scope was passed to the distal loop without resistance.

Fig. 1.

Plain abdominal radiograph showing absent small bowel gas and the large bowel containing gas (red arrow) with faecal shadows (green arrow). Yellow arrow: coiled nasogastric tube, orange arrow: pelvi-ureteric junction calculus.

Fig. 2.

Gastrograffin contrast study at 12 h showing contrast in the distended stomach (arrow) and no contrast in the small bowel.

Fig. 3.

Plain radiograph taken 24 h after the gastrograffin study showing contrast in the colon (arrow).

Fig. 4.

Gastroscopy showing an oedematous anastomotic site with a patent lumen (arrow).

As there was delayed passage of contrast to the distal bowel and patent anastomosis at endoscopy, a diagnosis of gastroparesis was made. An intra-abdominal collection was deemed less likely due to the absence of any ultrasonographic evidence. Initial management included resuscitation with intravenous fluids, electrolyte replacement and nasogastric tube insertion. The electrolyte imbalance was corrected on the day of admission. Total parenteral nutrition was commenced through a central line while monitoring for refeeding syndrome. Prokinetics such as metoclopromide and erythromycin were commenced after excluding a mechanical obstruction, in addition to proton pump inhibitors. However, there was no response for 10 days after admission with persistent daily nasogastric output of 0.5 – 0.8 L and intolerance to oral liquids. Therefore, a decision was taken to commence on a trial of neostigmine and failing which to consider revision of anastomosis.

Intravenous neostigmine was administered as an infusion of 0.4 mg/h for 4 h and repeated after 6 h for two days. Continuous cardiac monitoring was performed and no adverse cardiac events were noted. Immediate symptomatic relief was achieved with reduction of abdominal distension and bowel evacuation. The persistent hiccups were also relieved. He was commenced on oral liquids and gradually increased to solids after removal of the nasogastric tube and was discharged after 3 days. He developed acute urinary retention during the administration of neostigmine and was catheterised. Trial without catheter was successful after two days. He did not develop any other adverse effects due to neostigmine. At 6 months follow up, the patient was tolerating normal diet with no recurrence of symptoms.

3. Discussion

The management of post-surgical gastroparesis is challenging. Although various prokinetics are described for gastric motility disorders, the studies among post-gastrectomy patients with gastroparesis is limited and their efficacy in the post-operative setting is less known [2]^, [3]. Usually, gastroparesis after distal gastrectomy occurs in the immediate post-surgical period but delayed presentation has also been described [5].

Our patient tolerated oral intake in the immediate post-surgical period and was asymptomatic until 3 weeks following surgery. The delayed presentation led to a suspicion of either an intra-abdominal collection or mechanical obstruction. The delayed passage of oral contrast to the colon and the findings at gastroscopy ruled out a possibility of a mechanical obstruction. Although the anastomosis was patent, there was considerable anastomotic oedema which may have partly contributed to the presentation. The persistent hiccups were likely due to the irritation of the diaphragm by the grossly distended stomach.

Neostigmine has a short duration of action and is administered parenterally by slow intravenous or intramuscular injection or infusion. It has a broad adverse effect profile that includes life-threatening arrhythmias, bradycardia and heart blocks [6]. Therefore, intravenous administration has to be administered in a hospital setting with close cardiac monitoring with electrocardiogram. Although, the use of neostigmine is a well-established practice in colonic and small bowel pseudo-obstruction, and even in non-surgical gastric motility disorders, the utility in post-surgical gastroparesis is less known [7]. Although there may be ethical issues in using neostigmine for gastroparesis as it is not an established drug for gastroparesis, previous reports in the utility of small bowel pseudo-obstruction may be considered as justification for using it in our patient. Leow et al. reported a similar patient who developed post-surgical gastroparesis after 2 weeks of sleeve resection of a large GIST [8]. Conservative management with prokinetics for 10 days failed and the patient required a revision surgery with total gastrectomy and Roux-en-Y jejunal reconstruction [8]. We administered a trial of neostigmine before opting for revision surgery which was successful and avoided the additional surgical morbidity.

In our patient, the use of neostigmine infusion was safe and effective in the management of post-surgical gastroparesis after distal gastrectomy. There was no cardiac side effects observed but he developed acute urinary retention and was catheterised. He was on treatment for benign prostatic obstruction and had a previous history of trans-urethral resection of prostate and was on long term tamsulosin. This is the likely predisposing factor for the manifestation of this adverse effect. Trial without catheter was successful after two days. He did not develop any other adverse effects due to neostigmine.

4. Conclusion

Neostigmine infusion was safe and effective in the treatment of post-surgical gastroparesis after distal gastrectomy in our patient. The successful administration of neostigmine avoided the morbidity due to revision surgery. To date, there are no trials investigating the place of neostigmine for resistant gastroparesis after gastric surgery and future studies are warranted prior to routine use in clinical practice.

Abbreviation

GIST

Gastrointestinal stromal tumour

Consent

Written informed consent was obtained from the patients for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Ethical approval

Ethical approval is exempt/waived at our institution.

Funding

None declared.

Guarantor

DW, Professor in Surgery and Consultant Surgeon, University Surgical Unit, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka.

Research registration number

Not applicable.

CRediT authorship contribution statement

Authors UJ, KY, KR, AR and PP contributed to collection of information and writing of the manuscript. Authors UJ and DW contributed to writing of the manuscript and final approval. All authors read and approved the final version for publication.

Conflicts of interest

The authors declare that they have no competing interests.