A total of 275 articles were identified through searches in the 4 databases. After manual screening of titles and abstracts, and removal of duplicates, 22 articles were ultimately selected [5, 6, 12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31].

The workflow of the search was showed in Fig. 1, while summary of the articles was presented in Table 1.

Workflow of the study identification

Seven works were conducted in the USA, three in Korea, three in Canada, two in Turkey, three in Italy, and one each in the UK, Spain, Mexico, and Australia.

All included articles were case reports or small case series (1–10 patients), comprising a total of 54 patients (30 male and 24 female, mean age 8.03 ± 5.60 years, range 2 months–21 years).

Various underlying conditions were reported; 7 patients were classified as having primary CIPO, 15 had oncological diseases, 7 underwent abdominal transplant surgery, 3 underwent orthopedic surgery, 11 had genetic disorders, and 11 had other conditions (Table 2). Patients with CIPO without comorbidities were most frequently treated with pyridostigmine, whereas oncological patients were more often treated with neostigmine.

Notably, among the 54 patients, 13 developed CIPO following chemotherapy and 13 after surgery (Table 3). Neostigmine was the only drug administered in cases where CIPO occurred after chemotherapy, and it was also more commonly used in patients who developed CIPO following surgery.

The main symptoms reported included abdominal and intestinal loop distension, constipation, vomiting, abdominal pain, and reduced or absent bowel movements.

The diagnosis was mainly based on the radiological findings of the abdomen, showing bowel distention without mechanical obstruction; however, in a few articles the authors did not report the imaging findings for all the patients described [15, 22, 29, 30].

In 1 article, neostigmine and pyridostigmine were administered subsequentially [30], 13 works used neostigmine alone [16, 18,19,20,21,22,23,24,25,26,27,28, 32], and 7 used pyridostigmine alone [5, 6, 12,13,14,15, 17].

Neostigmine was primarily administered intravenously or subcutaneously. Pyridostigmine was administered orally in two patients, however, most of the studies did not report the route of administration (Table 4).

Effective pyridostigmine doses varied from 1 to 4 mg/kg/day for acute treatment and from 0.44 to 3.1 mg/kg/day for chronic therapy lasting months to years. Lower dosage (0.25 mg/kg/day) generally resulted in only partial effects. In a single case, a higher dose of 30 mg/kg/day was administered and was associated with symptomatic improvement. For acute management, neostigmine was effective at a subcutaneous dose of 0.01 mg/kg (for 1–3 doses). When administered as a continuous intravenous infusion, effective maximum doses were 0.005–0.011 mg/kg/h for approximately 1 day; in one case, a maximum dose of 0.05 mg/kg/h was reported (Table 1).

The duration of the treatment ranged from a single dose of pyridostigmine to more than 3 years of treatment, while neostigmine was administered for periods ranging from short intravenous infusion to 10 days. Symptom resolution was achieved in 36 cases (overall rate 66.7%, 56% when pyridostigmine was used, 81% when neostigmine was used), while in 7 cases improvement was partial (13%) and in 9 cases the therapy was ineffective (16.7%) (Table 5).

The reported outcomes used to define successful treatment included improvement of clinical symptoms, reduction of abdominal distension and pain, normalization of bowel movement and defecation, resolution of vomiting, increased tolerance or intake of oral feeding, and decreased hospitalization. Outcomes were defined as partial by the authors when there was no complete resolution of symptoms but only some ameliorations.

Nevertheless, pyridostigmine was not effective in an 18-year-old patient with no prior medical history, whose symptoms resolved only after an isolated small intestine transplant [14], and in a 2-month-old infant with CIPO onset at 3 days of life [17]. Moreover, it was not efficacious in a case of neurogenic CIPO, in a patient with ACTG2 related visceral myopathy, and in a child with mitochondrial disease [31]. Neostigmine was ineffective in a patient with cerebral palsy and spastic quadriparesis who developed CIPO after scoliosis surgery and was later subjected to an ileocecal resection due to a cecal perforation [20], in a heart-transplant patient whose symptoms resolved after 2 days with polyethylene glycol administration [22], and in two oncologic patients [28]. In the study where neostigmine and pyridostigmine were administered sequentially, the authors reported a shortening in the hospital length of stay and parenteral nutrition use, but did not describe the exact impact of the treatment on gastrointestinal symptoms [30].

When the patients were categorized according to the myopathic or neurogenic nature of their disorders, the success rates were lower with myopathic CIPO in respect to those with neurogenic CIPO. In the case where CIPO was nonspecific, symptom resolution was achieved in three out of eight patients (Table 6).

Few side effects were reported, and those described were generally mild, including abdominal pain, cramps, vomiting, salivation, diplopia, and bradycardia. In one case, diffuse erythema, a sensation of throat closure, and dyspnea following neostigmine infusion led to discontinuation of the treatment [25]. In another case, abdominal pain and cramps after pyridostigmine administration resulted in treatment discontinuation (Table 7) [15].

When assessing the risk of bias with the JBI tools, which are appropriately tailored for case reports and case series, most items were rated as low risk (Supplementary Table 2). However, it is important to consider that case series and case reports inherently presented potential biases due to their observational design and the absence of control arm.