Effect of coadministration of 10 mg/kg calcium chloride and neostigmine on extubation time: A randomized controlled trial.

INTRODUCTION AND OBJECTIVES: Some studies investigating the effect of calcium on neostigmine-induced recovery of neuromuscular blockade have shown that this combination promotes neuromuscular recovery, but does not significantly affect the incidence of postoperative residual curarization and time to extubation. This study aimed to evaluate the effects of 10 mg/kg calcium chloride co-administered with neostigmine on early recovery and time to extubation. PATIENTS AND METHODS: This prospective, randomized, double-blinded, placebo-controlled study included 88 ASA I-II patients aged between 18 and 65 years who were scheduled for elective surgery lasting at least 1 h under general anaesthesia in which 10 mg/kg of calcium chloride or the same volume of normal saline was co-administered with 5 µg/kg of neostigmine at the end of surgery. Time to extubation (time from neostigmine administration to extubation), time from neostigmine administration to TOF ratio (TOFr) 0.9 (neuromuscular recovery), and the incidence of residual neuromuscular blockade (RNMB) and other adverse effects were recorded. RESULTS: Median (Q1, Q3) extubation time was significantly shorter in the calcium group vs. the placebo group (6.5 min [5.52-7.43] vs. 9.78 min [8.35-11]), P < .001. Median neuromuscular recovery time in the calcium group was 5 min vs. 7.1 min in the placebo group, P < .001. Patients in the calcium group had significantly higher TOFr and lower incidence of RNMB at 5 and 10 min vs. the placebo group, and no significant side effects. CONCLUSION: Calcium chloride at a dose of 10 mg/kg co-administered with neostigmine promotes early neuromuscular recovery and reduces time to extubation by about 32%.

The effect of glycopyrrolate vs. atropine in combination with neostigmine on cardiovascular system for reversal of residual neuromuscular blockade in the elderly: a randomized controlled trial.

BACKGROUND: Glycopyrrolate-neostigmine (G/N) for reversing neuromuscular blockade (NMB) causes fewer changes in heart rate (HR) than atropine-neostigmine (A/N). This advantage may be especially beneficial for elderly patients. Therefore, this study aimed to compare the cardiovascular effects of G/N and A/N for the reversal of NMB in elderly patients. METHODS: Elderly patients aged 65-80 years who were scheduled for elective non-cardiac surgery under general anesthesia were randomly assigned to the glycopyrrolate group (group G) or the atropine group (group A). Following the last administration of muscle relaxants for more than 30 min, group G received 4 ug/kg glycopyrrolate and 20 ug/kg neostigmine, while group A received 10 ug/kg atropine and 20 ug/kg neostigmine. HR, mean arterial pressure (MAP), and ST segment in lead II (ST-II) were measured 1 min before administration and 1-15 min after administration. RESULTS: HR was significantly lower in group G compared to group A at 2-8 min after administration (P < 0.05). MAP was significantly lower in group G compared to group A at 1-4 min after administration (P < 0.05). ST-II was significantly depressed in group A compared to group G at 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, and 15 min after administration (P < 0.05). CONCLUSIONS: In comparison to A/N, G/N for reversing residual NMB in the elderly has a more stable HR, MAP, and ST-II within 15 min after administration.

Effects of magnesium sulphate on neostigmine-induced recovery from moderate neuromuscular blockade with rocuronium: a randomized controlled trial.

Magnesium enhances the effects of neuromuscular blocking agents. However, there is a paucity of evidence demonstrating possible effects of magnesium on neostigmine-induced recovery from neuromuscular blockade with rocuronium. This study compared the profiles of recovery from neuromuscular blockade between groups treated with magnesium (Group M) and placebo controls (Group C). Sixty-four patients were randomly allocated to Group M or Group C. Patients in Group M received a loading dose of 50 mg/kg magnesium and continuous infusion of 15 mg/kg/hr. Patients in Group C received a comparable amount of saline. Rocuronium at 0.6 mg/kg was used for tracheal intubation and 0.1 mg/kg of rocuronium was additionally administered to maintain train-of-four (TOF) status of 2-3 during surgery. At the end of surgery, neostigmine (50 µg/kg) plus glycopyrrolate (10 µg/kg) were administered, and the recovery time for TOF ratios of 0.7, 0.8, and 0.9 was measured. The primary outcome was the time from neostigmine administration to recovery with a TOF ratio of 0.9. In addition, rocuronium onset time (time from administration of rocuronium to 95% suppression of the first TOF twitch response), additional requirements for rocuronium and spontaneous recovery period (the time from administration of rocuronium to reappearance of the first TOF twitch response) were also measured. Neostigmine-induced recovery time was comparable between Group M and Group C (10.6 ± 4.3 vs. 9.1 ± 5.0 min, respectively, p = 0.22). The rocuronium onset time was shorter in Group M, and the spontaneous recovery period was longer in Group M. The amount of additional rocuronium administered was 27% lower in Group M, but this difference was not significant. Magnesium was not shown to prolong neostigmine-induced recovery time from neuromuscular blockade with rocuronium, however, it enhanced the clinical effects of rocuronium.

Optimal dose of neostigmine antagonizing cisatracurium-induced shallow neuromuscular block in elderly patients: a randomized control study.

BACKGROUND: Residual neuromuscular block after using neuromuscular blocking agents is a common and potentially harmful complication of general anesthesia. Neostigmine is a widely used antagonist, but its optimal dose for elderly patients is unclear. OBJECTIVES: To compare the optimal dosage and safety of neostigmine for reversing shallow residual block in elderly patients after cisatracurium-induced neuromuscular block. METHODS: A randomized controlled trial was conducted in 196 elderly patients undergoing non-cardiac surgery under general anesthesia with cisatracurium. Patients were assigned to receive either no neostigmine (control group) or neostigmine at 20 µg/kg, 40 µg/kg or 50 µg/kg when train-of-four (TOF) ratio reached 0.2 at the end of surgery. The primary outcome was the time to reach TOF ratio of 0.9 after administration. Secondary outcomes included TOF ratio at 10 min after administration, postoperative nausea and vomiting, postoperative cognitive impairment and post-anesthesia care unit (PACU) stay time. RESULTS: The time to reach TOF ratio of 0.9 in the 20 µg/kg, 40 µg/kg and 50 µg/kg groups was significantly shorter than the control group (H = 104.257, P < 0.01), and the time of 40 µg/kg group and 50 µg/kg group was significantly shorter than the 20 µg/kg group (P < 0.001). There was no significant difference between 40 µg/kg and 50 µg/kg groups (P = 0.249). The TOF ratio at 10 min after administration showed similar results. There were no significant differences among groups in postoperative nausea and vomiting, postoperative cognitive impairment or post-operation hospital stay. CONCLUSIONS: Timely use of neostigmine after general anesthesia in elderly patients can significantly shorten time of TOF value reaching 0.9, among which 40 µg/kg dosage may be a more optimized choice. TRIAL REGISTRATION: this study was registered on chictr.org.cn (ChiCTR2100054685, 24/12/2021).

Postoperative pulmonary complications after sugammadex reversal of neuromuscular blockade: a systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Sugammadex has been reported to lower the incidence of postoperative residual neuromuscular blockade. Despite the advantages, until recently the effects of sugammadex on postoperative pulmonary complications (PPCs) were controversial. We conducted a systematic review and meta-analysis to determine whether reversal with sugammadex was associated with a lower risk of PPCs compared with neostigmine. METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to May 2022. Randomized controlled trials (RCTs) and observational studies comparing PPCs in patients receiving sugammadex or neostigmine as reversal agent at the end of surgery were included. The primary outcomes focused on PPCs including desaturation, pneumonia, atelectasis, noninvasive ventilation (NIV) and reintubation. Trial sequential analysis was performed on the primary outcomes to confirm whether firm evidence was reached. RESULTS: Meta-analysis of included studies showed that the rate of desaturation (43.2% vs 45.0%, RR = 0.82; 95% CI 0.63 to 1.05; p = 0.11) were comparable between the two groups. When looking at other primary outcomes, significantly lower risk of pneumonia (1.37% vs 2.45%, RR = 0.65; 95% CI 0.49 to 0.85; p = 0.002), atelectasis (24.6% vs 30.4%, RR = 0.64; 95% CI 0.42 to 0.98; p = 0.04), NIV (1.37% vs 2.33%, RR = 0.65; 95% CI 0.43 to 0.98; p = 0.04) and reintubation (0.99% vs 1.65%, RR = 0.62; 95% CI 0.43 to 0.91; p = 0.01) in the sugammadex group were detected compared with the neostigmine group. CONCLUSIONS: We concluded that sugammadex is more effective at reducing the incidence of PPCs including pneumonia, atelectasis, NIV and reintubation compared with neostigmine. Further evidence, preferably from RCTs, is required to confirm these findings.

Subclinical involvement of eye movements detected by video-based eye tracking in myasthenia gravis.

BACKGRO UND: Ocular abnormalities in myasthenia gravis (MG) are characterized by severely limited movements and rapid saccades. Data about eye motility of MG patients whose ocular movements are apparently normal are lacking. Our study assessed the eye movement parameters in MG patients without clinical eye motility dysfunctions and investigated the effects of neostigmine administration on the eye motility in these patients. MATERIALS: In this longitudinal study, we screened all patients diagnosed with MG referring to the Neurologic Clinic of the University of Catania between October 1, 2019, and June 30, 2021. Ten age- and sex-matched healthy controls were enrolled. Patients underwent eye movement recording using the EyeLink1000 Plus® eye tracker at baseline and after 90 min from the intramuscular administration of neostigmine (0.5 mg). RESULTS: A total of 14 MG patients with no clinical signs of ocular motor dysfunction (64.3% men, with a mean age of 50.4 ± 14.4 years) were enrolled. At baseline, saccades in MG patients showed slower velocities and longer latencies compared to controls. Moreover, the fatigue test induced a reduction in saccadic velocity and an increase in latencies. After neostigmine administration, the ocular motility analysis showed shorter saccadic latencies and a significant improvement of velocities. CONCLUSIONS: Eye motility is impaired even in MG patients with no clinical evidence of ocular movement disturbance. Video-based eye tracking may detect subclinical involvement of eye movements in patients with MG.

Case Report: Successful Reversal of Residual Block with Sugammadex in a Patient Not Known to Have Myasthenia Gravis.

BACKGROUND Incomplete recovery from residual neuromuscular block agent (NMBA) after anesthesia is a serious adverse event in the post-anesthesia care unit. Acetylcholinesterase neostigmine is usually used to reverse residual neuromuscular blockade and facilitate spontaneous breathing and endotracheal extubation. CASE REPORT A 40-year-old woman received general anesthesia for strabismus correction surgery. At the end of surgery, repeated doses of neostigmine up to 85 µg/kg failed to reverse the residual neuromuscular blockade (train-of-four [TOF] ratio below 21%). Sugammadex (200 mg) provided immediate reversal, with the TOF ratio up to 100%. The patient regained spontaneous breathing, and the endotracheal tube was removed. After surgery, myasthenia gravis was diagnosed. CONCLUSIONS When unexpected prolonged neuromuscular blockade presents, the TOF ratio should be used to detect its depth and guide a reasonable dose of reversal agents. Anticholinesterase has a ceiling effect; once acetylcholinesterase activity is fully inhibited, administration of additional anticholinesterase can result in no further recovery. Furthermore, excessive acetylcholine can cause muscle weakness. In contrast, sugammadex is a selective reversal agent for steroidal NMBA, which works by encapsulation via tight water-soluble complexes with amino steroids (eg, rocuronium) rather than increasing acetylcholine at the neuromuscular junction. In this case, the recovery from moderate neuromuscular blockade by sugammadex was more effective and rapid than that by neostigmine. When refractory and prolonged residual neuromuscular blockade presents after repeated doses of anticholinesterase, sugammadex should be considered as an effective reversal agent. Particularly in cases of myasthenia gravis, sugammadex is superior to neostigmine for reversing rocuronium-induced NMBA in patients undergoing surgery.

Optimizing Reversal of Neuromuscular Block in Older Adults: Sugammadex or Neostigmine.

Residual neuromuscular paralysis, the presence of clinically significant weakness after administration of pharmacologic neuromuscular blockade reversal, is associated with postoperative pulmonary complications and is more common in older patients. In contemporary anesthesia practice, reversal of neuromuscular blockade is accomplished with neostigmine or sugammadex. Neostigmine, an acetylcholinesterase inhibitor, increases the concentration of acetylcholine at the neuromuscular junction, providing competitive antagonism of neuromuscular blocking drug and facilitating muscle contraction. Sugammadex, a modified gamma-cyclodextrin, antagonizes neuromuscular blockade by encapsulating rocuronium and vecuronium in a one-to-one ratio for renal clearance, a pharmacokinetic property that led to the recommendation that sugammadex not be administered to those with end-stage renal disease. While data are limited, reports suggest sugammadex is efficacious and well tolerated in individuals with reduced renal function. Sugammadex provides a more rapid and complete reversal of neuromuscular blockade than neostigmine. There is also accumulating evidence that sugammadex may provide a protective effect against the development of postoperative pulmonary complications, nausea, and vomiting, and that it may have beneficial effects on the rate of bowel and bladder recovery after surgery. Accordingly, sugammadex administration is beneficial for most older patients undergoing surgery.

A comparison between cisatracurium and rocuronium-induced neuromuscular block on laryngeal electromyography recovery after neostigmine reversal in a porcine model.

Background: Inducing and reversing neuromuscular block is essential to a positive outcome of thyroid surgery, with intraoperative neuromonitoring (IONM) being used to decrease recurrent and superior laryngeal nerve injuries and improve vocal outcome. Neostigmine is a non-specific broad-spectrum and inexpensive reversal agent for neuromuscular blocking agents (NMBAs). The aim of this porcine study was to explore the effect of neostigmine on electromyography (EMG) signal recovery profile following the commonly used NMBAs, cisatracurium and rocuronium. Methods: Twelve piglets were allocated into two groups with six piglets in each group. When stable baseline EMG signals were obtained, a neuromuscular block was induced by intravenous cisatracurium 0.2 mg/kg (group C) or rocuronium 0.6 mg/kg (group R) for each piglet. We compared laryngeal EMG tracing with spontaneous recovery (control) and neostigmine (0.04 mg/kg) reversal for each group. The time course of real-time laryngeal EMG signals was observed for 30 min from NMBA injection. Effects of neostigmine on EMG signal were assessed at 50% EMG recovery and by the maximum neuromuscular block recovery degree from the baseline value. Results: Neostigmine shortened the recovery time to 50% EMG amplitude in both group C (16.5 [2.5] vs. 29.0 [2.0] min, P<0.01) and group R (16.5[2.5] vs. 26.5 [1.5] min, P<0.05) compared to spontaneous recovery, respectively. Neostigmine reversal also enhanced the maximum degree of EMG amplitude recovery in both group C (83.6 [5.1] vs. 47.2 [6.1] %, P<0.01) and group R (85.6 [18.2]vs. 57.1 [6.3] %, P<0.05) compared to spontaneous recovery, respectively. The reversal effect of neostigmine did not differ significantly between cisatracurium and rocuronium. Conclusions: This porcine model demonstrated that neostigmine provides an adequate and timely IONM signal suppressed by both cisatracurium and rocuronium. These results can potentially expand the options for precision neuromuscular block management during IONM to improve vocal outcomes in thyroid surgery patients.

Effects of sugammadex and neostigmine on mucociliary clearance in general anesthesia.

OBJECTIVE: The aim of this study was to evaluate the effects of sugammadex and neostigmine used in general anesthesia on postoperative mucociliary clearance. PATIENTS AND METHODS: This prospective, randomized and double-blind study was performed on 60 non-smokers with ASA I-III underwent inguinal hernia repair under general anesthesia. Mucociliary clearance was assessed by nasal saccharine transit time (STT). After the preoperative STT measurement, the patients were taken to the operating room, and divided into two equal groups as group 1 and 2 (n= 30 for each group). Midazolam, propofol, and rocuronium were used in all patients. Anesthesia was maintained by sevoflurane at a flow rate of 6 lt/min (50% O2 - 50% N2O) with a minimum alveolar concentration of 1.3-1.5. After the surgical procedure, atropine-neostigmine (20 mcg/kg - 50 mcg/kg) and sugammadex (2 mg/kg) were administered to group 1 and group 2, respectively, and then the patients were extubated. The postoperative STT was measured in postoperative period. RESULTS: The mean age of the patients was 53 (±16) years, and 56 (93%) of them were male. There were no differences between the groups in terms of age, gender, height, weight, ASA score, and duration of anesthesia, duration of surgery, postoperative period, preoperative STT, and postoperative STT. However, when each group was evaluated separately, there was a statistically significant increase in the postoperative STT compared to the preoperative STT in both groups (p=0.005 for group 1, p<0.001 for group 2). CONCLUSIONS: The effects of sugammadex and neostigmine used in general anesthesia on postoperative mucociliary clearance are similar, and postoperative mucociliary clearance is delayed.

Early-Onset Myasthenia Gravis Following COVID-19 Vaccination.

As coronavirus disease 2019 (COVID-19) has spread worldwide, the rate of COVID-19 vaccination uptake is encouraging. Neurological complications associated with COVID-19 vaccines such as stroke, Guillain-Barré syndrome, and Bell's palsy have been reported. Recently, late-onset myasthenia gravis (MG) following COVID-19 vaccination has been reported. To date, however, there has been no evidence of increased risk of early-onset MG following COVID-19. Here, we report a case of a patient with new-onset MG that arose after receiving a COVID-19 vaccine. A 33-year-old woman suddenly experienced generalized weakness and diplopia on the evening she had received the second dose of the Pfizer-BioNTech COVID-19 vaccine. The temporal relationship suggests that this new-onset MG is related to the vaccination. It also implies that COVID-19 vaccination could trigger early-onset MG symptoms in patients at risk of MG.

Half-Dose Sugammadex After Neostigmine Versus Neostigmine as a Routine Reversal Agent: A Pilot Randomized Trial.

PURPOSE: The use of sugammadex at a lower dose after a routine reversal dose of neostigmine may prevent residual neuromuscular blockade (rNMB). Our goal was to investigate the effects of the use of half-dose sugammadex for reversing rNMB after administration of neostigmine, and compare these effects to a routine full-dose of neostigmine. DESIGN: Prospective, single-blinded, randomized trial. METHODS: Ninety-eight patients having lower abdominal tumor resection surgery under general anesthesia were randomized into two groups. Group N (Neostigmine) (n = 48) patients received standard reversal dose of intravenous neostigmine 0.05 mg/kg and atropine 0.02 mg/kg before extubationl Group N + S (Neostigmine + Sugammadex) (n = 50) patients received 1 mg/kg of intravenous sugammadex three minutes after a standard neostigmine reversal dose. The primary end-point was the incidence of a train-of-four (TOF) ratio less than 0.9 at tracheal extubation. Secondary end-points were periods between the start of administration of reversal agents and extubation or operating room discharge in minutes to achieve recovery of TOF ratio < 0.9 to 0.7 and TOF ratio ≥ 0.9. FINDINGS: The demographic data were not different between the two groups (P > .005). The incidence of rNMB presented as TOF ratio < 0.9 to 0.7 was present in 52% of Group N patients compared to 8% in Group N + S patients (P < .0001). The time to recovery between administering reversal and extubation as well as operating room discharge in Group N were; 18.52 ± 6.34 minutes and 23.27 ± 6.95 minutes, respectively, whereas; in Group N + S, they were; 12.86 ± 5.05 and 17.82 ± 4.99 minutes, respectively. (P < .0001, P < .0001, respectively). Adverse events were similar between groups (P > .05). CONCLUSIONS: A half-dose sugammadex (1 mg/kg) after full-dose reversal of neostigmine provides a lower incidence of rNMB and shorter recovery times as compared to full-dose neostigmine reversal agent. This practice is safe and effective in case of rNMB.

Investigation of potential neuropharmacological activity of neostigmine-glycopyrrolate for intraoperative neural monitoring in thyroid surgery.

Intraoperative neuromonitoring (IONM) is frequently used in thyroid surgery to reduce recurrent laryngeal nerve injury. The use of neuromuscular blockade agent to facilitate tracheal intubation, is a common cause of IONM failure. We performed a retrospective analysis to assess the efficacy of neostigmine-glycopyrrolate as a neuromuscular blockade reversal agent for IONM during thyroid surgery. Rocuronium (0.6 mg/kg) was administered for muscle relaxation. Neostigmine (2 mg) and glycopyrrolate (0.4 mg) were administered immediately after intubation. Cricothyroid muscle-twitch response upon external branch of superior laryngeal nerve stimulation and electromyography amplitudes of vagal and recurrent laryngeal nerves before (V1, R1) and after thyroid resection (V2, R2) were recorded. Fifty patients (23 males, 27 females) were included in the analysis. The diagnoses comprised 43 papillary thyroid carcinomas and seven benign diseases. The mean time between rocuronium injection and neostigmine-glycopyrrolate injection was 5.1 ± 1.2 min, and the mean time from neostigmine-glycopyrrolate injection to successful cricothyroid muscle twitching upon external branch of superior laryngeal nerve stimulation was 21.0 ± 4.5 min. All patients had V1 and R1 amplitudes of more than 500 µV each, with mean V1 and R1 amplitudes of 985.3 ± 471.6 µV and 1177.2 ± 572.7 µV, respectively. Neostigmine-glycopyrrolate was effectively used as a neuromuscular blockade reversal agent for IONM in thyroid surgeries without a significant increase in bucking events. Administration of neostigmine-glycopyrrolate immediately after intubation can be recommended for successful NMB reversal to facilitate IONM during thyroid surgery.

Sugammadex Reduces PACU Recovery Time after Abdominal Surgery Compared with Neostigmine.

OBJECTIVE: This study blindly evaluated sugammadex compared with neostigmine on length of stay in the postanesthesia care unit (PACU). METHODS: Fifty patients undergoing elective laparoscopic cholecystectomy or abdominal wall hernia repair consented to receive either sugammadex (2 mg/kg) or neostigmine (0.07 mg/kg) for the reversal of rocuronium neuromuscular blockade. Reversal agents were administered during surgical closing, and the train of four was measured until a twitch ratio of T4:T1 ≥ 0.9 was obtained to signify a robust reversal. Postreversal outcomes also were measured during PACU stay. Aldrete scores, pain visual analog scale score, and nausea were measured during the PACU stay. RESULTS: Patients receiving sugammadex experienced a shorter PACU stay at the time of discharge than patients receiving neostigmine, by an average of 12 minutes (P < 0.05). CONCLUSIONS: Sugammadex patients had a significantly shorter PACU stay.

Near-infrared fluorescent probe for evaluating the acetylcholinesterase effect in the aging process and dietary restriction via fluorescence imaging.

Dietary restriction (DR), as a natural intervention, not only benefits the neuroendocrine system, but also has an antiaging action. Acetylcholinesterase (AChE) is one of the most important bioactive substances and plays a major part in choline changes in the aging process. Thus, we aim to evaluate the effect of DR on AChE in the brains of aging animals. In this study, we synthesize a NIR fluorescent probe BD-AChE for the real-time and in situ monitoring of AChE level changes in living cells and living mice, notably in brains. In situ visualization with BD-AChE verified a decrease in the AchE level in the brains of mice aging models. Evidently, the prepared probe has the excellent capability of measuring AChE variation in the brains of aging mice with DR via NIR fluorescence bioimaging, indicating that long-term DR can effectively affect AChE levels in the brain. The attenuation of AChE level in the brain of aging mice after DR could be helpful in infering the advantageous impact of DR on age-related neurodegenerative disease, as a better treatment alternative in the future.

The effects of acetylcholinesterase inhibitors on morbidity after general anesthesia and surgery.

Non-depolarizing neuromuscular blocking agents are used during general anesthesia to facilitate intubation and optimize surgical conditions. When patients leave the operating room after surgery, postoperative residual neuromuscular block occurs frequently, increasing vulnerability to respiratory complications such as hypoxemia and unplanned postoperative mechanical ventilation. To restore neuromuscular transmission and skeletal muscle strength, anesthesiologists typically administer peripherally acting acetylcholinesterase inhibitors such as neostigmine. However, neostigmine's desirable effects have a narrow therapeutic range. Even at recommended dose (15-50 µg/kg), neostigmine induces nicotinic (upper airway muscle weakness leading to dysphagia and upper airway obstruction, and decreased maximum inspiratory airflow) and muscarinic (blurred vision, bronchial constriction, abdominal cramping and nausea) side effects. Recent data have questioned as to whether neostigmine reversal of neuromuscular blockade improves relevant patient outcomes such as postoperative respiratory and perioperative cardiovascular complications. A central strategy to avoid side effects of neuromuscular blocking agents is their judicious use based on quantitative monitoring of neuromuscular transmission using repetitive peripheral nerve stimulation (train-of-four ratio). Peripherally acting acetylcholinesterase inhibitors such as neostigmine should then only be administered when indicated and dosed based on results of the train-of-four ratio.

SUGAMMADEX versus neostigmine after ROCURONIUM continuous infusion in patients undergoing liver transplantation.

BACKGROUND: Rapid neuromuscular block reversal at the end of major abdominal surgery is recommended to avoid any postoperative residual block. To date, no study has evaluated sugammadex performance after rocuronium administration in patients undergoing liver transplantation. This is a randomized controlled trial with the primary objective of assessing the neuromuscular transmission recovery time obtained with sugammadex versus neostigmine after rocuronium induced neuromuscular blockade in patients undergoing orthotopic liver transplantation. METHODS: The TOF-Watch SX®, calibrated and linked to a portable computer equipped with TOF-Watch SX Monitor Software®, was used to monitor and record intraoperative neuromuscular block maintained with a continuous infusion of rocuronium. Anaesthetic management was standardized as per our institution's internal protocol. At the end of surgery, neuromuscular moderate block reversal was obtained by administration of 2 mg/kg of sugammadex or 50 mcg/kg of neostigmine (plus 10 mcg/kg of atropine). RESULTS: Data from 41 patients undergoing liver transplantation were analysed. In this population, recovery from neuromuscular block was faster following sugammadex administration than neostigmine administration, with mean times±SD of 9.4 ± 4.6 min and 34.6 ± 24.9 min, respectively (p < 0.0001). CONCLUSION: Sugammadex is able to reverse neuromuscular block maintained by rocuronium continuous infusion in patients undergoing liver transplantation. The mean reversal time obtained with sugammadex was significantly faster than that for neostigmine. It is important to note that the sugammadex recovery time in this population was found to be considerably longer than in other surgical settings, and should be considered in clinical practice. TRIAL REGISTRATION: ClinicalTrials.govNCT02697929 (registered 3rd March 2016).

Neostigmine treatment induces neuroprotection against oxidative stress in cerebral cortex of asthmatic mice.

During chronic inflammatory disease, such asthma, leukocytes can invade the central nervous system (CNS) and together with CNS-resident cells, generate excessive reactive oxygen species (ROS) production as well as disbalance in the antioxidant system, causing oxidative stress, which contributes a large part to neuroinflammation. In this sense, the aim of this study is to investigate the effects of treatment with neostigmine, known for the ability to control lung inflammation, on oxidative stress in the cerebral cortex of asthmatic mice. Female BALB/cJ mice were submitted to asthma model induced by ovalbumin (OVA). Control group received only Dulbecco's phosphate-buffered saline (DPBS). To evaluate neostigmine effects, mice received 80 µg/kg of neostigmine intraperitoneally 30 min after each OVA challenge. Our results revealed for the first time that treatment with neostigmine (an acetylcholinesterase inhibitor that no crosses the BBB) was able to revert ROS production and change anti-oxidant enzyme catalase in the cerebral cortex in asthmatic mice. These results support the communication between the peripheral immune system and the CNS and suggest that acetylcholinesterase inhibitors, such as neostigmine, should be further studied as possible therapeutic strategies for neuroprotection in asthma.

The effect of vitamin D status on different neuromuscular blocker agents reverse time

Background/aim: This study is aimed to investigate the effects of vitamin D levels on sugammadex and neostigmine reversal times. Material and methods: Eighty patients between the ages of 18 and 65 years, with ASA I-III status who were undergoing surgery under general anesthesia were included in the study. A double blind fashion was used to randomly divide all the patients into two groups. At the end of the operation, sugammadex 2 mg/kg was administered to one group (Group sugammadex) and atropine and neostigmine was administered to the other group (Group neostigmine) intravenously. In the data analysis stage, the group was divided into two subgroups according to sugammadex and group neostigmine in itself, with vitamin D levels above and below 30 ng/mL. Statistical analysis was performed on these 4 groups (Group neostigmine and vitamin D < 30 ng/mL), (Group neostigmine and vitamin D ≥ 30 ng/mL), ( Group sugammadex and vitamin D < 30 ng/mL), (Group sugammadex and vitamin D ≥ 30 ng/mL). When two responses to train of four (TOF) stimulation were taken, the following times were recorded until extubation phase. The time until TOF value 50%, 70%, 90%, and extubation were recorded. Results: There were statistically significant differences between Group sugammadex and vitamin D < 30 ng/mL and Group sugammadex and vitamin D ≥ 30 ng/mL (P = 0.007) for extubation times and 50% TOF reach times (P = 0.015). However, there was no difference observed between Group neostigmine and vitamin D < 30 ng/mL and Group neostigmine and vitamin D ≥ 30 ng/mL (P = 0.999). Conclusion: Vitamin D deficiency is important for anesthesiologists in terms of muscle strength and extubation time. Vitamin D deficiency seems to affect sugammadex reverse times but seems not to affect neostigmine reverse times. This conclusion needs further studies.

Randomised controlled trial of sugammadex or neostigmine for reversal of neuromuscular block on the incidence of pulmonary complications in older adults undergoing prolonged surgery.

BACKGROUND: Residual neuromuscular block has been associated with postoperative pulmonary complications. We hypothesised that sugammadex reduces postoperative pulmonary complications in patients aged ≥70 yr having surgery ≥3 h, compared with neostigmine. METHODS: Patients were enrolled in an open-label, assessor-blinded, randomised, controlled trial. At surgical closure, subjects were equally randomised to receive sugammadex 2 mg kg-1 or neostigmine 0.07 mg kg-1 (maximum 5 mg) for rocuronium reversal. The primary endpoint was incidence of postoperative pulmonary complications. Secondary endpoints included residual paralysis (train-of-four ratio <0.9 in the PACU) and Phase 1 recovery (time to attain pain control and stable respiratory, haemodynamic, and neurological status). The analysis was by intention-to-treat. RESULTS: Of the 200 subjects randomised, 98 received sugammadex and 99 received neostigmine. There was no significant difference in the primary endpoint of postoperative pulmonary complications despite a signal towards reduced incidence for sugammadex (33% vs 40%; odds ratio [OR]=0.74; 95% confidence interval [CI]=[0.40, 1.37]; P=0.30) compared with neostigmine. Sugammadex decreased residual neuromuscular block (10% vs 49%; OR=0.11, 95% CI=[0.04, 0.25]; P<0.001). Phase 1 recovery time was comparable between sugammadex (97.3 min [standard deviation, sd=54.3]) and neostigmine (110.0 min [sd=62.0]), difference -12.7 min (95% CI, [-29.2, 3.9], P=0.13). In an exploratory analysis, there were fewer 30 day hospital readmissions in the sugammadex group compared with the neostigmine group (5% vs 15%; OR=0.30, 95% CI=[0.08, 0.91]; P=0.03). CONCLUSIONS: In older adults undergoing prolonged surgery, sugammadex was associated with a 40% reduction in residual neuromuscular block, a 10% reduction in 30 day hospital readmission rate, but no difference in the occurrence of postoperative pulmonary complications. Based on this exploratory study, larger studies should determine whether sugammadex may reduce postoperative pulmonary complications and 30 day hospital readmissions. CLINICAL TRIAL REGISTRATION: NCT02861131.