Possible mechanisms related to contraction of the bovine iris sphincter in the presence of acetylcholine and carbachol

Using tension-recording methods, we compared the effects of acetylcholine (Ach) and carbachol on the bovine iris sphincter. The isolated muscle strips were mounted in a 0.2 ml organ bath, through which Krebs solution at 36 °C flowed continuously. There was a tenthousandfold difference in potency between carbachol and Ach in this tissue. Neostigmine or eserine, acetylcholinesterase (AchE) inhibitors, produced a larger contraction of the muscle than did Ach. Ach-induced contractions were potentiated by low doses of anti-AchEs and were inhibited by atropine.This in vitro study suggests that Ach and/or endogenous chemical agents may be spontaneously released from tissues and that AchE activities in this tissue strongly inhibit or mask the Ach action, probably in order to protect the nerve terminals from released Ach.     

Conditions to optimise the reversal action of neostigmine upon a vecuronium-induced neuromuscular block

Background: Since neostigmine was introduced for reversal of neuromuscular block, there has been controversy about the optimum dose for antagonizing neuromuscular block. The purpose of this study was to characterise recovery of neuromuscular transmission following a vecuronium-induced block 15 min after neostigmine administration using different stimulation patterns, and to determine the effects of different doses of neostigmine given at various pre-reversal twitch heights. Methods: Adductor pollicis (AP) mechanical activity in response to low (0.1 and 2 Hz) and high (50 and 100 Hz) frequency stimulation, was recorded 15 min after 20, 40 and 80 μg/kg neostigmine, given to reverse a vecuronium-induced block at 10, 25 and 50% pre-reversal twitch height (TH). Fifty four ASA class I and II anaesthetised (methohexital, fentanyl, N₂O/O₂) young adult patients were studied and randomly allocated into 9 groups of 6 patients each. Results: In contrast to twitch height (TH) and residual force after 50 Hz, 5 s tetanic stimulation (RF50_Hz), the greater sensitivity of train-of-four (TOF) ratio and residual force after 100 Hz, 5 s tetanic stimulation (RF100_Hz) points out the best reversal conditions (prereversal TH and the optimal neostigmine dose) (P<0.001, two-way analysis of variance). The highest reversal scores (about 0.9 TOF ratio and RF100_Hz) were obtained when 40 μg/ kg of neostigmine was given at 25 and 50% TH. A 0.9 TOF ratio was also observed when 40 μg/kg of neostigmine was given at 10% TH, but, under these conditions, RF100_Hz was only 0.6 (P<0.05, Duncan test). Conclusion: To optimise the reversal action of neostigmine in order to obtain the highest neuromuscular transmission recovery (0.9 TOF ratio and RF100_Hz) during a vecuronium-induced neuromuscular block, the 40 μg/kg dose has to be given at 25 to 50% recovery of TH.     

HPLC 法测定甲硫酸新斯的明注射液的含量

目的：建立 HPLC 法测定甲硫酸新斯的明注射液的含量。方法用 Agilent ZORBAX Eclipse XDB C18（250 mm ×4．6 mm,5μm）,以0．05 moL·L －1磷酸二氢钾溶液（用磷酸调节 pH 为3．0）—乙腈（90∶10）为流动相,流速为1．0 mL·min －1,检测波长为215 nm。结果甲硫酸新斯的明线性范围为在0．102～1．02 g·L －1（r ＝0．9999）;平均回收率为99．57％,RSD 为0．93％。结论该方法灵敏,快速,结果准确,可用于甲硫酸新斯的明注射液的质量控制。     

A randomised controlled trial comparing deep neuromuscular blockade reversed with sugammadex with moderate neuromuscular block reversed with neostigmine

Deep neuromuscular block aims to improve operative conditions during laparoscopic surgery with a lower intra-abdominal pressure. Studies are conflicting on whether meaningful improvements in quality of recovery occur beyond emergence, and whether lower intra-abdominal pressure is achieved. In this pragmatic randomised trial with 1:1 allocation, adults undergoing elective laparoscopic surgery were allocated to moderate neuromuscular block reversed with neostigmine, or deep neuromuscular block reversed with sugammadex. Allocation was revealed to the anaesthetist only. Primary outcome was cognitive recovery of the Postoperative Quality of Recovery Scale, 7 days after surgery. Secondary outcomes included recovery in other domains of the Postoperative Quality of Recovery Scale at 15 min and 40 min; days 1, 3, 7, 14; and 1 and 3 months after surgery. Chi-square test was used for the primary outcome, and generalised linear mixed model for recovery over time between groups. Of 350 participants randomised, 140 (deep) and 144 (moderate) were analysed for the primary outcome. There was no difference in the Postoperative Quality of Recovery Scale cognitive domain at day 7 (deep 92.9% vs. moderate 91.8%, OR 1.164; 95%CI 0.486–2.788, p = 0.826), or at any other time-point. No significant difference was observed for physiological, emotive, activities of daily living, nociception, or overall recovery. Length of stay in the recovery area (mean (SD) deep 108 (58) vs. moderate 109 (57) min, p = 0.78) and hospital (1.8 (1.9) vs. 2.6 (3.5) days, p = 0.019) was not different. Intra-abdominal pressure and surgical operating conditions were not different between groups. Deep neuromuscular block did not improve quality of recovery compared with moderate neuromuscular block in operative laparoscopic surgery over a 1-h duration.     

Intrathecal administration of liposomal neostigmine prolongs analgesia in mice

BACKGROUND: There is substantial evidence that cholinomimetic drugs increase pain threshold. However, the profound side effects of these agents have limited their clinical use either as analgesics or as analgesic adjuncts. A delivery system that would assure a slow and sustained drug release may be of value in ameliorating the problem of untoward effects. METHODS: The acetylcholinesterase inhibitor neostigmine was encapsulated into multilamellar lipid vesicles composed of phosphocholine and cholesterol. Three doses of plain or liposomal neostigmine were administered by the intrathecal route to mice (n=8-10/group), and analgesic duration was quantified by tail flick test. The doses were chosen based on preliminary experiments, which showed the maximum tolerated intrathecal doses of plain and liposomal neostigmine formulation were 0.625 microg and 80 microg, respectively. Two other doses for each formulation were then derived by 1:1 serial dilutions. Results were compared using survival analysis. RESULTS: The median antinociceptive duration for plain neostigmine was 0.33, 0.99 and 1.0 h for the 0.115, 0.312 and 0.625 microg doses, respectively. For the liposomal formulation, the median antinociceptive duration was 1.0, 1.5 and 6.0 h for the 20, 40 and 80 microg doses, respectively. CONCLUSIONS: Liposomal neostigmine provides prolonged spinal antinociception, and permits the safe administration of a relatively large dose, because drug is gradually released from the liposomal depot. This technology holds promise for the development of a clinically useful neostigmine formulation to provide spinal analgesia.     

长托宁或阿托品与新斯的明合用拮抗肌肉松驰药残余作用时对血流动力学影响的比较

OBJECTIVE: To investigate the effects of penehyclidine hydrochloride(PH)/atropine combined with neostigmine for antagonizing residual neuromuscular block on the hemodynamics. METHODS: Eighty patients with elective upper abdominal surgery were randomized equally into PH group and atropine group. Five minutes after the completion of surgery, PH 0.02 mg/kg (in PH group) or atropine 0.02 mg/kg (in atropine group) in combination with neostigime 0.03 mg/kg were given intravenously to reverse the residual neuromuscular block. The heart rate (HR), mean arterial pressure (MAP) and end-tidal CO(2) pressure (P(ET)CO(2)) were recorded 5 min before anesthesia induction, 1 min before injection and 2, 5, 10, and 15 min after injection, respectively. RESULTS: During the investigation, HR in PH group did not undergo conspicuous changes (P>0.05). HR after the injection was markedly faster than that before the injection in atropine group (P<0.01) and did not recover till 15 min after the injection (P>0.05). MAP and P(ET)CO(2) showed no evident changes and no significant difference was observed between the two groups during the investigation (P>0.05). CONCLUSION: Compared with atropine, PH does not obviously affect HR and BP, but atropine may accelerate HR.     

七氟醚呼气末浓度对新斯的明拮抗罗库溴铵肌松作用的影响

目的研究七氟醚呼气末浓度对新斯的明拮抗罗库溴铵肌松作用的影响。方法48例择期行颌面部全麻手术病人随机分成四组：异丙酚、瑞芬太尼麻醉维持组（P组异丙酚输注速度2~5μg.kg-1.min-1）,0.4MAC七氟醚、瑞芬太尼麻醉维持组（S-1组,维持七氟醚呼气末体积浓度0.7%）、0.7MAC七氟醚、瑞芬太尼麻醉维持组（S-2组,维持七氟醚呼气末体积浓度1.0%）和1.0MAC七氟醚、瑞芬太尼麻醉维持组（S-3组,维持七氟醚呼气末体积浓度1.7%）,首量2倍ED95罗库溴铵保持肌松。当TOF的T1恢复到25%时,给予新斯的明0.04 mg.kg-1.min-1。记录T1和TOFr恢复过程。结果给予新斯的明后S-2组和S-3组的T1恢复时程基本相似,但恢复时间均明显比S-1组长。而S-1组T1恢复到50%、75%、95%和100%的时间和P组基本相同。结论0.4MAC七氟醚对罗库溴铵肌松效应无明显影响。0.7MAC七氟醚能增强罗库溴铵的肌松效应,影响程度与1MAC七氟醚相似,延迟新斯的明拮抗罗库溴铵肌松作用的时间。     

Effects of the 5-HT3 antagonist cilansetron vs placebo on phasic sigmoid colonic motility in healthy man: a double-blind crossover trial

AIMS: 5-hydroxytryptamine3 receptor antagonists act antiemetically and slow colonic transit. This study evaluated effects of the high-affinity 5-HT3 antagonist, cilansetron, on fasting, meal-and anticholinesterase-stimulated phasic contractile activity of the human sigmoid colon as well as on bowel habits and stool consistency. METHODS: Five female and seven male healthy volunteers received, during three 7 day periods separated by 7 day wash-out periods, 4 mg cilansetron, 8 mg cilansetron or placebo three times daily orally under random, double-blind, crossover conditions. On day 8 of each treatment period, motility 20-40 cm from the anal verge was recorded using five pressure sensors spaced at 5 cm intervals. After a basal 30 min, subjects swallowed a further dose of the scheduled treatment; 60 min later, blood was taken for the determination of plasma cilansetron levels. Thereafter, subjects ingested a 4200 kJ meal and 250 ml sweetened mallow tea (166 kJ); 90 min after meal onset, 1 mg neostigmine was administered intramuscularly and motility recording was continued for 60 min RESULTS: Phasic contractile activity and intraluminal base-line pressure increased postprandially and more so after neostigmine. With cilansetron, the area under the pressure curve as the primary outcome variable and the number of contractions were significantly greater than with placebo (P = 0.005), amplitude and duration of contractions and base-line pressure were not affected. The effects of the two cilansetron dosages did not differ. With cilansetron, stool tended to become firmer. No adverse effects were observed. Plasma levels were highest with 8 mg cilansetron. CONCLUSIONS: Cilansetron slightly augments meal-stimulated and markedly neostigmine-stimulated phasic motility of the sigmoid colon. When administered over 7 days, it tends to increase stool consistency and is well tolerated.     

Caudal additives for postoperative pain management in children: S(+)-ketamine and neostigmine

BACKGROUND: The aim of the present pilot study was to compare the analgesic efficacy of S(+)-ketamine either alone or in combination with neostigmine for caudal blockade in pediatric surgery. METHODS: A total of 40 children were randomly assigned to receive after induction of general anesthesia either caudal S(+)-ketamine 1 mg.kg(-1) (group K, n = 20) or caudal S (+)-ketamine 0.5 mg.kg(-1) plus neostigmine 10 microg.kg(-1) (group KN, n = 20). Anesthesia was maintained with sevoflurane and a laryngeal mask airway (LMA), no additional analgesics were administered. Postoperative pain and sedation were assessed by the Children's Hospital of Eastern Ontario Pain Score and Ramsay scale for 24 h. RESULTS: No statistical difference in duration of analgesia and sedation was found. Mean duration of postoperative analgesia was 18 +/- 9.4 h in group K and 21.8 +/- 6.7 h in group KN. There was a significantly higher incidence of postoperative vomiting after administration of caudal ketamine with neostigmine (30% group KN Vs 0% group K; P < 0.05). CONCLUSIONS: This pilot study demonstrates equianalgesic effects on postoperative pain relief in children with both caudal S(+)-ketamine 1 mg.kg(-1) and caudal S(+)-ketamine 0.5 mg.kg(-1) plus neostigmine 10 microg.kg(-1). Further studies are required to confirm adoption of caudal neostigmine into routine clinical practice.