Pyridostigmine in Pediatric Intestinal Pseudo-obstruction: Case Report of a 2-year Old Girl and Literature Review

( Giovanni Di Nardo ),( Federica Viscogliosi ),( Francesco Esposito ),( Vincenzo Stanghellini ),( Maria Pia Villa ),( Pasquale Parisi ),( Alessia Morlando ),( Girolamo Cal ),( Roberto De Giorgio ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2019 Journal of Neurogastroenterology and Motility (JNM Vol.25 No.4

Pediatric chronic intestinal pseudo-obstruction is a rare disorder characterized by a severe impairment of gastrointestinal motility leading to intestinal obstruction symptoms in the absence of mechanical causes. The diagnosis is usually clinical and diagnostic work is usually aimed to rule out mechanical obstruction and to identify any underlying diseases. Treatment is challenging and requires a multidisciplinary effort. In this manuscript we describe the youngest child successfully treated with the orally administrable, longacting, reversible anti-cholinesterase drug, pyridostigmine. Like other drugs belonging to cholinesterase inhibitors, pyridostigmine enhances gut motility by increasing acetylcholine availability in the enteric nervous system and neuro-muscular junctions. Based on the direct evidence from the reported case, we reviewed the current literature on the use of pyridostigmine in severe pediatric dysmotility focusing on intestinal pseudo-obstruction. The overall data emerged from the few published studies suggest that pyridostigmine is an effective and usually well tolerated therapeutic options for patients with intestinal pseudo-obstruction. More specifically, the main results obtained by pyridostigmine included marked reduction of abdominal distension, reduced need of parenteral nutrition, and improvement of oral feeding. The present case and review on pyridostigmine pave the way for eagerly awaited future randomized controlled studies testing the efficacy of cholinesterase inhibitors in pediatric severe gut dysmotility. (J Neurogastroenterol Motil 2019;25:508-514)

Neuromuscular blockade reversal with sugammadex versus pyridostigmine/ glycopyrrolate in laparoscopic cholecystectomy: a randomized trial of effects on postoperative gastrointestinal motility

안지현,노희윤,김은주,이지향,우경윤,김현겸 대한마취통증의학회 2020 Korean Journal of Anesthesiology Vol.73 No.2

Background: Acetylcholinesterase inhibitors (e.g., pyridostigmine bromide) are used for neuromuscular blockade (NMB) reversal in patients undergoing surgery under general anesthesia (GA). Concurrent use of anticholinergic agents (e.g., glycopyrrolate) decreases cholinergic side effects but can impede bowel movements. Sugammadex has no cholinergic effects; its use modifies recovery of gastrointestinal (GI) motility following laparoscopic cholecystectomy compared to pyridostigmine/glycopyrrolate. This study evaluated the contribution of sugammadex to the recovery of GI motility compared with pyridostigmine and glycopyrrolate. Methods: We conducted a prospective study of patients who underwent laparoscopic cholecystectomy. Patients were randomly allocated to the experimental group (sugammadex, Group S) or control group (pyridostigmine-glycopyrrolate, Group P). After anesthesia (propofol and rocuronium, and 2% sevoflurane), recovery was induced by injection of sugammadex or a pyridostigmine-glycopyrrolate mixture. As a primary outcome, patients recorded the time of their first passage of flatus (‘gas-out time’) and defecation. The secondary outcome was stool types. Results: One-hundred and two patients participated (Group S [n = 49], Group P [n = 53]). Mean time from injection of NMB reversal agents to gas-out time was 15.03 (6.36–20.25) h in Group S and 20.85 (16.34–25.86) h in Group P (P = 0.001). Inter-group differences were significant. Time until the first defecation as well as types of stools was not significantly different. Conclusions: Sugammadex after laparoscopic cholecystectomy under GA resulted in an earlier first postoperative passage of flatus compared with the use of a mixture of pyridostigmine and glycopyrrolate. These findings suggest that the use of sugammadex has positive effects on the recovery of GI motility.

Treatment of Dysphagia with Pyridostigmine Bromide in a Patient with the Pharyngeal- Cervical-Brachial Variant of Guillain-Barré Syndrome

Kwang Lae Lee,이주강,임오경,박기덕 대한재활의학회 2012 Annals of Rehabilitation Medicine Vol.36 No.1

A 24-year-old male developed bulbar palsy, ophthalmoplegia, ptosis, and shoulder weakness bilaterally 2 weeks after he had experienced an upper respiratory infection. The electrodiagnostic study demonstrated axonal polyradiculoneuropathy. The repetitive nerve stimulation study (RNS) showed no significant decrement of the compound muscle action potentials (CMAPs). The videofluoroscopic swallowing study (VFSS) showed severe impairment of the pharyngeal phase of swallowing. He was diagnosed as having the pharyngeal-cervical-brachial variant of Guillain-Barré syndrome. The patient’s dysphagia was not improved for 3 months. A follow up RNS showed a signifi cant decrement of the CMAPs. Pyridostigmine bromide was tried to improve the dysphagia. Th e patient showed immediate improvement of his dysphagia on the VFSS after the trial with pyridostigmine bromide. Pyridostigmine bromide was given before each meal for 8 days and he showed continuous improvement of his dysphagia. Th e follow up VFSS after 3 months showed complete recovery of dysphagia.

Role of a Novel Pyridostigmine Bromide-Phospholipid Nanocomplex in Improving Oral Bioavailability

Qun-you Tan,Jing-qing Zhang,Ni-ni Hu,Guo-dong Liu,Hua-feng Yin,Li Zhang,Hong Wang,Lu-yang Lu 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.3

A novel pyridostigmine bromide (PB)-phospholipid nanocomplex (PBPLC) was prepared to increase the bioavailability of PB. A central composite design approach was employed for process optimization. The physicochemical properties of PBPLC were investigated by means of differential scanning calorimetry, ultraviolet spectroscopy, Fourier transformed infrared spectroscopy and the n-octano/water partition coefficient. The intestinal permeability of PBPLC was observed via a single pass intestinal perfusion in rats. After oral administration of PBPLC, the concentrations of PB at predetermined time points were determined by HPLC, and the pharmacokinetic parameters were computed by DAS 2.1.1 software. Multiple linear regression analysis for process optimization revealed that the optimal PBPLC was obtained when the values of X1, X2, and X3 were 8, 40oC, and 4 mg/mL, respectively. The average particle size and zeta potential of PBPLC with the optimized formulation were 204.60 nm and −25.12 mV, respectively. Non-covalent interactions between PB and phospholipids were found in the PBPLC. The n-octanol/water partition coefficient of PBPLC was substantially increased. PBPLC had better intestinal permeability in comparison with free PB. Mean plasma drug concentration-time curves of PBPLC and free PB after oral administration were both in accordance with the two-compartment open model. The values of pharmacokinetic parameters of PBPLC and free PB were the peak time (Tmax) 2 h vs 2 h, the maximum concentration (Cmax) 22.79 μg/mL vs 6.00 μg/mL, and the value of the area under the concentration vs time curve (AUC0-∞) 7128.21 μg·min/mL vs 1772.36 μg·min/mL, respectively. In conclusion, compared with free PB, PBPLC remarkably improves the oral bioavailability of PB, which is likely due to its higher lipophilicity and permeability.

Effect of neuromuscular blockade reversal by pyridostigmine on spectral entropy values during recovery from desflurane anesthesia: a prospective, randomized, double-blind, controlled trial

변성혜,김유진,류재훈 대한마취통증의학회 2016 Korean Journal of Anesthesiology Vol.69 No.3

Background: According to several studies investigating the relationship between muscle activity and electroencephalogram results, reversal of neuromuscular blockade (NMB) may affect depth of anesthesia indices. Therefore, we investigated the effect of pyridostigmine on these indices via spectral entropy. Methods: Fifty-six patients scheduled for thyroidectomy or parotidectomy were included in this study and randomized into two groups. At the start of skin suturing, the desflurane concentration was adjusted to 4.2 vol% in both groups. Following this, the pyridostigmine group (group P, n = 28) was administered pyridostigmine 0.2 mg/kg mixed with glycopyrrolate 0.04 mg/kg, while the control group (group C, n = 28) received normal saline. Entropy values (response entropy [RE] and state entropy [SE]), train of four (TOF) ratio, and end-tidal desflurane concentration were recorded from point of drug administration to 15 minutes post-drug administration. Results: Mean RE values at 15 minutes, when the maximum effect of pyridostigmine was anticipated, showed a statistically significant difference between groups (53.8 ± 10.5 in group P and 48.0 ± 8.8 in group C; P = 0.030). However, mean SE at 15 minutes showed no significant difference between the two groups (P = 0.066). At 15 minutes, there were significant differences in the TOF ratio between the two groups (P < 0.001). Conclusions: NMB reversal by pyridostigmine significantly increased RE values but not SE values. This finding suggests that spectral entropy may be a useful alternative tool for monitoring anesthetic depth during recovery from anesthesia in the presence of electromyogram activity.

Comparison of sugammadex and pyridostigmine bromide for reversal of rocuronium-induced neuromuscular blockade in short-term pediatric surgery: a prospective randomized study

안지현,김은주,이지향,김현,손종철,허준영,우경윤 대한마취통증의학회 2019 Anesthesia and pain medicine Vol.14 No.3

Background: Sugammadex reverses rocuronium-induced neuromuscular blockade quickly and effectively. Herein, we compared the efficacy of sugammadex and pyridostigmine in the reversal of rocuronium-induced light block or minimal block in pediatric patients scheduled for elective entropion surgery. Methods: A prospective randomized study was conducted in 60 pediatric patients aged 2–11 years who were scheduled for entropion surgery under sevoflurane anesthesia. Neuromuscular blockade was achieved by administration of 0.6 mg/kg rocuronium and assessed using the train-of-four (TOF) technique. Patients were randomly assigned to 2 groups receiving either sugammadex 2 mg/kg or pyridostigmine 0.2 mg/kg and glycopyrrolate 0.01 mg/kg at the end of surgery. Primary outcomes were time from administration of reversal agents to TOF ratio 0.9 and TOF ratio 1.0. Time from the administration of reversal agents to extubation and postoperative adverse events were also recorded. Results: There were no significant differences in the demographic variables. Time from the administration of reversal agents to TOF ratio 0.9 and TOF ratio 1.0 were significantly shorter in the sugammadex group than in the pyridostigmine plus glycopyrrolate group: 1.30 ± 0.84 vs. 3.53 ± 2.73 min (P < 0.001) and 2.75 ± 1.00 vs. 5.73 ± 2.83 min (P < 0.001), respectively. Extubation time was shorter in the sugammadex group. Adverse events, such as skin rash, nausea, vomiting, and postoperative residual neuromuscular blockade (airway obstruction), were not statistically different between the two groups. Conclusions: Sugammadex provided more rapid reversal of rocuronium-induced neuromuscular blockade in pediatric patients undergoing surgery than did pyridostigmine plus glycopyrrolate.

고인습성 약물인 피리도스티그민의 마이크로캅셀화에 의한 분체 특성의 개선

김대석,김인화,정석재,심창구 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.1

The purpose of this study is to microencapsulate a highly hygroscopic drug, pyridostigmine bromide (PB), with a waterproof wall material, in order to increase the flowability of the drug particles. Polyvinylacetaldiethylaminoacetate (AEA), Eugragit E and Eugragit RS were examined as the wall materials. Microcapsules containing PB were prepared by the evaporation technique in an acetone/liquid paraffin system using aluminum tristearate as a core material, and evaluated for drug encapsulation efficiency, surface morphology, particle size and drug dissolution. The encapsulation of PB in the wall material was almost complete. Among the wall materials examined, AEA exhibited the most excellency in shape, surface texture, flowability, size distribution of microcapsules. Above results suggest that AEA would be a potential wall material for microcapsulation of highly hygroscopic drugs, such as PB. Through microencapsulation with AEA, inconvenience of handling of PB powders encountered in the process of weighing and packing the powders to tableting die or capsule body could be greatly improved.

Response to neuromuscular blockade with rocuronium during general anesthesia in a patient with dermatomyositis - A case report -

김세연,이용배 대한마취통증의학회 2018 Anesthesia and pain medicine Vol.13 No.1

Dermatomyositis is an idiopathic inflammatory myopathy characterized by skin changes and muscle weakness. Depending on the involvement of various muscles, dermatomyositis can cause aspiration pneumonia, ventilatory impairment, and heart failure. Several reports have documented normal or prolonged neuromuscular blockade following administration of different non-depolarizing neuromuscular blockers in patients with dermatomyositis. We observed delayed onset of blockade and prolonged recovery following administration of 0.6 mg/kg rocuronium in a patient with dermatomyositis. However, when the train-of-four ratio reached 0.3, the patient was administered pyridostigmine and glycopyrrolate, which led to normal response to reversal of rocuronium. The patient was extubated without respiratory complications. The outcomes of this case indicate that response to the usual dosage of muscle relaxants in patients with dermatomyositis might be different from that in patients without this condition. Anesthesiologists should pay attention to preoperative cardiorespiratory evaluation and intraoperative neuromuscular monitoring.

Current use of neuromuscular blocking agents and antagonists in Korea: a 2018 survey

김진선,한정우,이재호,최재문,김하정,성태윤,김용범,신용섭,양홍석 대한마취통증의학회 2019 Anesthesia and pain medicine Vol.14 No.4

Background: Neuromuscular blocking agents (NMBAs) and neuromuscular monitoring in anesthetic management are integral for endotracheal intubation, better visualization of the surgical field, and prevention of residual neuromuscular blockade and pulmonary complications. Sugammadex is a drug that reduces risk of residual neuromuscular blockade, with more rapid recovery compared to anticholinesterase. The purpose of this study was to investigate current usage status of NMBAs and antagonist with neuromuscular monitoring, among anesthesiologists in Korea. Methods: Anesthesiologists working in Korea were invited to participate in an online survey via email January 2–February 28, 2018. The questionnaire consisted of 45 items, including preferred NMBAs, antagonists, neuromuscular monitoring, and complications related to the use sugammadex. A total of 174 responses were analyzed. Results: Rocuronium was a commonly used NMBA for endotracheal intubation (98%) of hospitals, and maintenance of anesthesia (83.3%) in of hospitals. Sugammadex, pyridostigmine, and neostigmine were used in 89.1%, 87.9%, and 45.4% of hospitals. Neuromuscular monitoring was employed in 79.3% of hospitals; however only 39.7% of hospitals used neuromuscular monitoring before antagonist administration. Usual dosage range of sugammadex was 2.1–4 mg/kg in 35.1% of hospitals, within 2 mg/kg in 34.5% of hospitals, and 1 vial regardless of body weight in 22.4% of hospitals. Sugammadexrelated complications were encountered by 14.9% of respondents. Conclusions: This survey indicates several minor problems associated with the use of antagonists and neuromuscular monitoring. However, most anesthesiologists appear to have appropriate information regarding the usage of NMBAs and sugammadex.