Protective effect of valerian extract capsule (VEC) on ethanol- and indomethacin-induced gastric mucosa injury and ameliorative effect of VEC on gastrointestinal motility disorder.

CONTEXT: Valerian extract capsule (VEC) is an effective Chinese patent medicine used for gastrointestinal (GI) diseases. OBJECTIVE: To investigate the detailed pharmacological activity for VEC clinical effects in GI diseases. MATERIALS AND METHODS: Sprague-Dawley rats were divided into six groups: control, model, and drug-treated (VEC-L, VEC-M, VEC-H, and teprenone). Rats were orally administered VEC (124, 248, 496 mg/kg) and teprenone (21.43 mg/kg) for 3 consecutive days. After 1 h, the five groups (except the control group) were orally given ethanol (10 mL/kg) for 1 h or indomethacin (80 mg/kg) for 7 h. The spasmolytic activity of VEC (0.01-1 mg/mL) on ACh/BaCl2-induced New Zealand rabbit smooth muscle contraction was performed. The C57BL/6 mice carbon propelling test evaluated the effects of VEC (248-992 mg/kg) on intestinal motility in normal and neostigmine/adrenaline-induced mice. RESULTS: Compared with the model group, VEC treatment reduced the gastric lesion index and mucosal damage. Further experiments showed that the pathological ameliorative effect of VEC was accompanied by augmentation of the enzymatic antioxidant system and cytoprotective marker (COX-1, p < 0.01; PGI2 p < 0.05;), along with the alleviation of the levels of MPO (ethanol: 15.56 ± 0.82 vs. 12.15 ± 2.60, p < 0.01; indomethacin: 9.65 ± 3.06 vs. 6.36 ± 2.43, p < 0.05), MDA (ethanol: 1.66 ± 0.44 vs. 0.81 ± 0.58, p < 0.01; indomethacin: 1.71 ± 0.87 vs. 1.09 ± 0.43, p < 0.05), and inflammatory mediators. VEC decreased the high tone induced by ACh/BaCl2 and promoted intestinal transit in normal and neostigmine/adrenaline-induced mice. DISCUSSION AND CONCLUSIONS: VEC showed a potential gastroprotective effect, suggesting that VEC is a promising phytomedicine for the treatment of GI diseases.

Identifying high dose neostigmine as a risk factor for post-operative respiratory complications: a case-control study.

INTRODUCTION: Neostigmine, an acetylcholinesterase inhibitor, is used to reverse the effects of non-depolarizing neuromuscular blocking agents. Inappropriate dosing of neostigmine can lead to post-operative respiratory complications. Post-operative respiratory complications are associated with major morbidity and mortality. The purpose of this case-control study was to determine neuromuscular blockade-related risk factors associated with post-operative respiratory complications (specifically, reintubation, respiratory insufficiency, hypoxia, and/or aspiration). MATERIAL AND METHODS: We performed an Institutional Review Board-approved case-control study of all patients who underwent a general anesthetic requiring neuromuscular blockade at Tufts Medical Center between March 22, 2013 and June 1, 2019. Cases were patients who experienced post-operative complications. We identified 58 controls and 116 cases from a database of 130,178 patients during the 74-month study period. RESULTS: After adjusting for covariates, the administration of high dose neostigmine (> 60 mg per kg ideal body weight) was associated with increased odds of post-operative respiratory complications (odds ratio = 8.2; 95% CI: 2.5-26.6, P < 0.001). Rocuronium dose and the use of train-of-four peripheral nerve stimulator were not associated with post-operative respiratory complications. CONCLUSIONS: High dose neostigmine was identified as an independent risk factor for post-operative respiratory complications. Our study suggests that inappropriate dosing of neostigmine continues to be a problem despite growing evidence of an association with respiratory complications.

Low-Dose or High-Dose Rocuronium Reversed with Neostigmine or Sugammadex for Cesarean Delivery Anesthesia: A Randomized Controlled Noninferiority Trial of Time to Tracheal Intubation and Extubation.

BACKGROUND: Rocuronium for cesarean delivery under general anesthesia is an alternative to succinylcholine for rapid-sequence induction of anesthesia because of the availability of sugammadex for reversal of neuromuscular blockade. However, there are no large well-controlled studies in women undergoing general anesthesia for cesarean delivery. The aim of this noninferiority trial was to determine whether rocuronium and sugammadex confer benefit in time to tracheal intubation (primary outcome) and other neuromuscular blockade outcomes compared with succinylcholine, rocuronium, and neostigmine in women undergoing general anesthesia for cesarean delivery. METHODS: We aimed to enroll all women undergoing general anesthesia for cesarean delivery in the 2 participating university hospitals (Brno, Olomouc, Czech Republic) in this single-blinded, randomized, controlled study. Women were randomly assigned to the ROC group (muscle relaxation induced with rocuronium 1 mg/kg and reversed with sugammadex 2-4 mg/kg) or the SUX group (succinylcholine 1 mg/kg for induction, rocuronium 0.3 mg/kg for maintenance, and neostigmine 0.03 mg/kg for reversal of the neuromuscular blockade). The interval from the end of propofol administration to tracheal intubation was the primary end point with a noninferiority margin of 20 seconds. We recorded intubating conditions (modified Viby-Mogensen score), neonatal outcome (Apgar score <7; umbilical artery pH), anesthesia complications, and subjective patient complaints 24 hours after surgery. RESULTS: We enrolled 240 parturients. The mean time to tracheal intubation was 2.9 seconds longer in the ROC group (95% confidence interval, -5.3 to 11.2 seconds), noninferior compared with the SUX group. Absence of laryngoscopy resistance was greater in the ROC than in the SUX groups (ROC, 87.5%; SUX, 74.2%; P = 0.019), but there were no differences in vocal cord position (P = 0.45) or intubation response (P = 0.31) between groups. No statistically significant differences in incidence of anesthesia complications or in neonatal outcome were found (10-minute Apgar score <7, P = 0.07; umbilical artery pH, P = 0.43). The incidence of postpartum myalgia was greater in the SUX group (ROC 0%; SUX 6.7%; P = 0.007). The incidence of subjective complaints was lower in the ROC group (ROC, 21.4%; SUX, 37.5%; P = 0.007). CONCLUSIONS: We conclude that rocuronium for rapid-sequence induction is noninferior for time to tracheal intubation and is accompanied by more frequent absence of laryngoscopy resistance and lower incidence of myalgia in comparison with succinylcholine for cesarean delivery under general anesthesia.

Analgesic effects of intrathecal neostigmine in perianal surgery.

BACKGROUND AND OBJECTIVE: In recent human and animal studies, intrathecal administration of various doses of neostigmine produces analgesia without neurotoxicity. The aim was to examine the effects of intrathecal neostigmine and bupivacaine in patients undergoing perianal surgery under spinal anaesthesia. METHODS: The patients were randomly allocated into three groups of 15: Group 1 (controls) received hyperbaric bupivacaine 10 mg + dextrose 5%, 1 mL, to a total volume of 3 mL; Group 2 received hyperbaric bupivacaine 10 mg + neostigmine 25 microg in dextrose 5%, 1 mL, to a total volume of 3 mL; and Group 3 received hyperbaric bupivacaine 10 mg + neostigmine 50 microg in dextrose 5%, 1 mL, to a total volume of 3 mL. RESULTS: The onset of sensory block was significantly earlier for Group 2 and 3 patients compared with Group 1 patients (P < 0.05). The full time to recovery of motor block and sensory block was significantly longer in Group 3 compared with Group 1 (P < 0.05). In Group 3, the average time until the first dose of tramadol was longer than Group 1 (P < 0.05). The incidence rate of nausea and vomiting was significantly higher in Groups 2 and 3 than in Group 1 (P < 0.05). CONCLUSIONS: The use of intrathecal neostigmine as an analgesic drug in perianal surgery is unsatisfactory because of prolonged motor blockade and nausea.

Hazards of neostigmine in patients with neuromuscular disorders. Report of two cases.

In a 57-yr-old female with dystrophia myotonica, attempts to reverse residual non-depolarizing block with neostigmine 1.0 mg were only partially effective and the administration of the further dose (0.5 mg) produced long-lasting muscle weakness. The train-of-four response of this patient resembled that of the depolarizing block and suggested an alteration in the electrical properties of the muscle membrane. A 50-yr-old male with a 30-yr history of progressive muscle dystrophy, exhibited a tonic response to neostigmine in the evoked mechanomyogram during recovery from partial neuromuscular block. It is concluded that the type of reaction to neostigmine in patients with neuromuscular disease in unpredictable.

[Neostigmine and dehiscence of intestinal anastomoses (author's transl)]. / Neostigmin und Insuffizienz intestinaler Anastomosen.

In a study from 1968, anastomotic leakage was reported to be nine times as frequent if neostigmine was used for reversal of curare action than in control patients. Subsequent studies did not confirm this finding although it is not disputed that neostigmine activates bowel peristalsis. Both animal experiments and clinical observations indicate that anastomoses in undamaged bowel, if properly done, withstand all kinds of hyperperistalsis. However, it cannot entirely be excluded that coincident pathologic conditions (cachexia, damaged bowel, chronic steroid medication, anaemia etc.) may occur, in which neostigmine administration is unsafe. Appropriate anaesthesiological techniques to avoid the need for neostigmine include titration of the individual relaxant requirement by means of a peripheral nerve stimulator, preference of intermediate or short-acting nondepolarizing muscle relaxants and primary postoperative mechanical ventilation. If nevertheless reversal of residual nondepolarizing block is decided, it should be performed with deep halothane anaesthesia still maintained and by means of an anticholinesterase agent with little muscarinic side effect such as edrophonium (0.5-1.0 mg/kg).

Cholinomimetic teratogens: studies with chicken embryos.

The cholinomimetic compounds carbachol, decamethonium, neostigmine, succinylcholine, trimethylphenylammonium, and others were tested for their interference with normal chick development. All these compounds led to abnormalities of the cervical vertebrae; at higher dosage interference with normal morphogenesis involved the whole vertebral column. Hypoplasia of the leg muscles occurred with lower incidence. Responses, tested with carbachol, rose from 24 to 72 and 96 h, then declined to 120 h of incubation. Two of the cholinometic compounds used in combined treatment produced a high degree of synergism. Gallamine, benzoquinomium, butyrylcholine, and bethanechol had protective effects. Acetylcholine, at high dosage, caused defects different from the above. It is suggested that the cholinomimetic teratogens interfere with normal development by displacing acetylcholine from its receptors or by forming complexes with it.