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The Cochrane Database of Systematic... Aug 2017Acetylcholinesterase inhibitors, such as neostigmine, have traditionally been used for reversal of non-depolarizing neuromuscular blocking agents. However, these drugs... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acetylcholinesterase inhibitors, such as neostigmine, have traditionally been used for reversal of non-depolarizing neuromuscular blocking agents. However, these drugs have significant limitations, such as indirect mechanisms of reversal, limited and unpredictable efficacy, and undesirable autonomic responses. Sugammadex is a selective relaxant-binding agent specifically developed for rapid reversal of non-depolarizing neuromuscular blockade induced by rocuronium. Its potential clinical benefits include fast and predictable reversal of any degree of block, increased patient safety, reduced incidence of residual block on recovery, and more efficient use of healthcare resources.
OBJECTIVES
The main objective of this review was to compare the efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade caused by non-depolarizing neuromuscular agents in adults.
SEARCH METHODS
We searched the following databases on 2 May 2016: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (WebSPIRS Ovid SP), Embase (WebSPIRS Ovid SP), and the clinical trials registries www.controlled-trials.com, clinicaltrials.gov, and www.centerwatch.com. We re-ran the search on 10 May 2017.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published, or language. We included adults, classified as American Society of Anesthesiologists (ASA) I to IV, who received non-depolarizing neuromuscular blocking agents for an elective in-patient or day-case surgical procedure. We included all trials comparing sugammadex versus neostigmine that reported recovery times or adverse events. We included any dose of sugammadex and neostigmine and any time point of study drug administration.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles and abstracts to identify trials for eligibility, examined articles for eligibility, abstracted data, assessed the articles, and excluded obviously irrelevant reports. We resolved disagreements by discussion between review authors and further disagreements through consultation with the last review author. We assessed risk of bias in 10 methodological domains using the Cochrane risk of bias tool and examined risk of random error through trial sequential analysis. We used the principles of the GRADE approach to prepare an overall assessment of the quality of evidence. For our primary outcomes (recovery times to train-of-four ratio (TOFR) > 0.9), we presented data as mean differences (MDs) with 95 % confidence intervals (CIs), and for our secondary outcomes (risk of adverse events and risk of serious adverse events), we calculated risk ratios (RRs) with CIs.
MAIN RESULTS
We included 41 studies (4206 participants) in this updated review, 38 of which were new studies. Twelve trials were eligible for meta-analysis of primary outcomes (n = 949), 28 trials were eligible for meta-analysis of secondary outcomes (n = 2298), and 10 trials (n = 1647) were ineligible for meta-analysis.We compared sugammadex 2 mg/kg and neostigmine 0.05 mg/kg for reversal of rocuronium-induced moderate neuromuscular blockade (NMB). Sugammadex 2 mg/kg was 10.22 minutes (6.6 times) faster then neostigmine 0.05 mg/kg (1.96 vs 12.87 minutes) in reversing NMB from the second twitch (T2) to TOFR > 0.9 (MD 10.22 minutes, 95% CI 8.48 to 11.96; I = 84%; 10 studies, n = 835; GRADE: moderate quality).We compared sugammadex 4 mg/kg and neostigmine 0.07 mg/kg for reversal of rocuronium-induced deep NMB. Sugammadex 4 mg/kg was 45.78 minutes (16.8 times) faster then neostigmine 0.07 mg/kg (2.9 vs 48.8 minutes) in reversing NMB from post-tetanic count (PTC) 1 to 5 to TOFR > 0.9 (MD 45.78 minutes, 95% CI 39.41 to 52.15; I = 0%; two studies, n = 114; GRADE: low quality).For our secondary outcomes, we compared sugammadex, any dose, and neostigmine, any dose, looking at risk of adverse and serious adverse events. We found significantly fewer composite adverse events in the sugammadex group compared with the neostigmine group (RR 0.60, 95% CI 0.49 to 0.74; I = 40%; 28 studies, n = 2298; GRADE: moderate quality). Risk of adverse events was 28% in the neostigmine group and 16% in the sugammadex group, resulting in a number needed to treat for an additional beneficial outcome (NNTB) of 8. When looking at specific adverse events, we noted significantly less risk of bradycardia (RR 0.16, 95% CI 0.07 to 0.34; I= 0%; 11 studies, n = 1218; NNTB 14; GRADE: moderate quality), postoperative nausea and vomiting (PONV) (RR 0.52, 95% CI 0.28 to 0.97; I = 0%; six studies, n = 389; NNTB 16; GRADE: low quality) and overall signs of postoperative residual paralysis (RR 0.40, 95% CI 0.28 to 0.57; I = 0%; 15 studies, n = 1474; NNTB 13; GRADE: moderate quality) in the sugammadex group when compared with the neostigmine group. Finally, we found no significant differences between sugammadex and neostigmine regarding risk of serious adverse events (RR 0.54, 95% CI 0.13 to 2.25; I= 0%; 10 studies, n = 959; GRADE: low quality).Application of trial sequential analysis (TSA) indicates superiority of sugammadex for outcomes such as recovery time from T2 to TOFR > 0.9, adverse events, and overall signs of postoperative residual paralysis.
AUTHORS' CONCLUSIONS
Review results suggest that in comparison with neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular block regardless of the depth of the block. Sugammadex 2 mg/kg is 10.22 minutes (˜ 6.6 times) faster in reversing moderate neuromuscular blockade (T2) than neostigmine 0.05 mg/kg (GRADE: moderate quality), and sugammadex 4 mg/kg is 45.78 minutes (˜ 16.8 times) faster in reversing deep neuromuscular blockade (PTC 1 to 5) than neostigmine 0.07 mg/kg (GRADE: low quality). With an NNTB of 8 to avoid an adverse event, sugammadex appears to have a better safety profile than neostigmine. Patients receiving sugammadex had 40% fewer adverse events compared with those given neostigmine. Specifically, risks of bradycardia (RR 0.16, NNTB 14; GRADE: moderate quality), PONV (RR 0.52, NNTB 16; GRADE: low quality), and overall signs of postoperative residual paralysis (RR 0.40, NNTB 13; GRADE: moderate quality) were reduced. Both sugammadex and neostigmine were associated with serious adverse events in less than 1% of patients, and data showed no differences in risk of serious adverse events between groups (RR 0.54; GRADE: low quality).
Topics: Adult; Androstanols; Atracurium; Cholinesterase Inhibitors; Humans; Neostigmine; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Randomized Controlled Trials as Topic; Rocuronium; Sugammadex; Time Factors; Vecuronium Bromide; gamma-Cyclodextrins
PubMed: 28806470
DOI: 10.1002/14651858.CD012763 -
Critical Care (London, England) Mar 2022Intra-abdominal hypertension (IAH) in acute pancreatitis (AP) is associated with deterioration in organ function. This trial aimed to assess the efficacy of neostigmine... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Intra-abdominal hypertension (IAH) in acute pancreatitis (AP) is associated with deterioration in organ function. This trial aimed to assess the efficacy of neostigmine for IAH in patients with AP.
METHODS
In this single-center, randomized trial, consenting patients with IAH within 2 weeks of AP onset received conventional treatment for 24 h. Patients with sustained intra-abdominal pressure (IAP) ≥ 12 mmHg were randomized to receive intramuscular neostigmine (1 mg every 12 h increased to every 8 h or every 6 h, depending on response) or continue conventional treatment for 7 days. The primary outcome was the percent change of IAP at 24 h after randomization.
RESULTS
A total of 80 patients were recruited to neostigmine (n = 40) or conventional treatment (n = 40). There was no significant difference in baseline parameters. The rate of decrease in IAP was significantly faster in the neostigmine group compared to the conventional group by 24 h (median with 25th-75th percentile: -18.7% [- 28.4 to - 4.7%] vs. - 5.4% [- 18.0% to 0], P = 0.017). This effect was more pronounced in patients with baseline IAP ≥ 15 mmHg (P = 0.018). Per-protocol analysis confirmed these results (P = 0.03). Stool volume was consistently higher in the neostigmine group during the 7-day observational period (all P < 0.05). Other secondary outcomes were not significantly different between neostigmine and conventional treatment groups.
CONCLUSION
Neostigmine reduced IAP and promoted defecation in patients with AP and IAH. These results warrant a larger, placebo-controlled, double-blind phase III trial. Trial registration Clinical Trial No: NCT02543658 (registered August /27, 2015).
Topics: Acute Disease; Humans; Intra-Abdominal Hypertension; Neostigmine; Pancreatitis
PubMed: 35241135
DOI: 10.1186/s13054-022-03922-4 -
Anaesthesia May 2023
Topics: Humans; Neostigmine; Sugammadex; Cholinesterase Inhibitors; Postoperative Complications; Neuromuscular Blockade
PubMed: 36599659
DOI: 10.1111/anae.15961 -
Anesthesia Progress Apr 2022Reversal agents are defined as any drug used to counteract the pharmacologic effects of another drug. Several pharmacologic antagonists serve as essential drugs in the... (Review)
Review
Reversal agents are defined as any drug used to counteract the pharmacologic effects of another drug. Several pharmacologic antagonists serve as essential drugs in the contemporary practices of sedation providers and anesthesiologists. Reversal or "antidote" drugs, such as flumazenil and naloxone, are often used in unintentional overdose situations involving significant benzodiazepine- and/or opioid-induced respiratory depression. Within the context of skeletal muscle relaxation, neostigmine and sugammadex are routinely used to reverse the effects of nondepolarizing neuromuscular blocking agents. In addition, the alpha-adrenergic antagonist phentolamine is used in dentistry as a local anesthetic reversal agent, decreasing its duration of action by inducing vasodilation. This review article discusses the pharmacology, uses, practical implications, adverse effects, and precautions needed for flumazenil, naloxone, neostigmine, sugammadex, and phentolamine within the context of sedation and anesthesia practice for dentistry.
Topics: Anesthesia, Dental; Anesthetics; Humans; Neostigmine; Sugammadex
PubMed: 35377935
DOI: 10.2344/anpr-69-01-09 -
British Journal of Anaesthesia Jan 2023In 2020, the Sugammadex vs Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications (STRONGER) study provided evidence for the first...
In 2020, the Sugammadex vs Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications (STRONGER) study provided evidence for the first time that use of sugammadex is associated with fewer postoperative pulmonary complications than use of neostigmine. In a recent publication in the British Journal of Anaesthesia, a secondary analysis of the same data, the Association Between Neuromuscular Blockade Reversal Agent Choice and Postoperative Pulmonary Complications (STIL-STRONGER) study, has produced similar evidence of the advantages of sugammadex over neostigmine in high-risk and older patients undergoing prolonged, elective surgery. Here we consider the implications of the detailed statistical analysis used in these two studies and how its limitations could possibly have enhanced the statistical differences between the two drugs with respect to postoperative pulmonary complications.
Topics: Humans; Cholinesterase Inhibitors; Neostigmine; Neuromuscular Blockade; Neuromuscular Blocking Agents; Postoperative Complications; Sugammadex
PubMed: 36182557
DOI: 10.1016/j.bja.2022.08.021 -
European Review For Medical and... Jun 2022The aim of this study was to evaluate the effects of sugammadex and neostigmine used in general anesthesia on postoperative mucociliary clearance. (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Adult; Aged; Anesthesia, General; Female; Humans; Male; Middle Aged; Mucociliary Clearance; Neostigmine; Prospective Studies; Sugammadex
PubMed: 35776029
DOI: 10.26355/eurrev_202206_29067 -
Pain Research & Management 2022Pentazocine produces a wide variety of actions in the treatment of perioperative analgesia. Neostigmine is a cholinesterase inhibitor used to antagonize the residual...
BACKGROUND
Pentazocine produces a wide variety of actions in the treatment of perioperative analgesia. Neostigmine is a cholinesterase inhibitor used to antagonize the residual effects of muscle relaxants and also produces an analgesic effect.
OBJECTIVES
To investigate the analgesic effects of intrathecally injected pentazocine and neostigmine and their interaction.
METHODS
Sprague-Dawley rats were used to test the analgesic effect of pentazocine and neostigmine using the paw formalin pain model and the incision mechanical allodynia model. Pentazocine (3, 10, 30, and 100 g), neostigmine (0.3, 1, 3, and 10 g) or a pentazocine-neostigmine mixture were separately injected to evaluate their antinociceptive effects alone on the treatment groups. The corresponding control group received an intrathecal injection containing the same volume of saline. The formalin pain test, or the plantar incision pain behavior test were performed 30 minutes later. Isobolographic analysis was used to evaluate the interaction between pentazocine and neostigmine. Intrathecally administered selective mu-opioid receptor antagonist CTAP, selective kappa-opioid receptor antagonist nor-Binaltorphimine (nor-BNI), nonselective opioid receptor antagonist naloxone, and muscarinic acetylcholine receptor antagonist atropine were also used to test the possible interaction mechanism. These antagonists were used 30 minutes before the pentazocine and neostigmine mixtures which were intrathecally injected.
RESULTS
Intrathecally administered pentazocine (3, 10, 30, and 100 g) and neostigmine (0.3, 1, 3, and 10 g) alone had a marked dose-related impact on suppressing the biphasic responses in the formalin test. Pentazocine (3, 10, 30, and 100 g) and neostigmine (0.3, 1, 3, and 10 g) alone attenuated the mechanical allodynia in a plantar incision model in a dose-dependent manner. Isobolographic analysis revealed that the mixture of intrathecal pentazocine and neostigmine synergistically decreased both phase I and II activity in the formalin test and mechanical allodynia in the plantar incision model. Pretreatment of intrathecally administered nor-BNI, naloxone, atropine, but not CTAP, antagonized the analgesic effect of the pentazocine-neostigmine mixture.
CONCLUSIONS
All of these results suggest that the combined application of pentazocine and neostigmine is an effective way to relieve pain from formalin and acute incision mechanical allodynia. The synergistic effect between pentazocine and neostigmine is mostly attributed to the kappa-opioid receptor and the cholinergic receptor in the spinal cord.
Topics: Analgesics; Animals; Atropine Derivatives; Clonidine; Formaldehyde; Humans; Hyperalgesia; Naloxone; Narcotic Antagonists; Neostigmine; Pain; Pentazocine; Rats; Rats, Sprague-Dawley
PubMed: 35646201
DOI: 10.1155/2022/4819910 -
Anesthesiology Aug 2018
Topics: Neostigmine
PubMed: 30020186
DOI: 10.1097/ALN.0000000000002296 -
Anesthesiology Aug 2018
Topics: Humans; Muscle Weakness; Neostigmine
PubMed: 30020187
DOI: 10.1097/ALN.0000000000002297 -
Annals of Palliative Medicine Dec 2021The purpose of this study was to evaluate the clinical effects and safety of neostigmine for the postoperative recovery of gastrointestinal function. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The purpose of this study was to evaluate the clinical effects and safety of neostigmine for the postoperative recovery of gastrointestinal function.
METHODS
We performed a literature search of multiple databases [PubMed, Web of Science, Cochrane Library and China National Knowledge Internet (CNKI)] to retrieve studies comparing the postoperative gastrointestinal function of neostigmine and control groups. Review Manager 5.2 was applied for the analysis of heterogeneity, sensitivity, and bias.
RESULTS
After screening the articles, 17 trials involving 1,589 postoperative patients that met the eligibility criteria were included. The results suggested that neostigmine improved the first passage of flatus [standard mean difference (SMD) =-3.00; 95% confidence interval (CI): (-4.03, -1.97); P<0.001), first defecation [SMD =-3.75; 95% CI: (-5.25, -2.24); P<0.001], time of bowel sound recovery [SMD =-3.42; 95% CI: (-4.49, -2.36), P<0.001], and gastrointestinal function recovery [risk ratio (RR) =1.84; 95% CI: (1.19, 2.86); P=0.007]. Compared to the control group, the neostigmine group had lower rates of abdominal distention [RR =0.39; 95% CI: (0.18, 0.87); P=0.02; I2=76%] and overall adverse events [RR =0.49; 95% CI: (0.29, 0.82); P=0.007]. However, two groups had no difference in postoperative nausea and vomiting (PONV) [RR =0.50; 95% CI: (0.21, 1.23); P=0.13], and respiratory complications [RR =0.96; 95% CI: (0.20, 4.53); P=0.96]. Sensitivity and publication bias analyses showed that these results were robust and exhibited little publication bias.
DISCUSSION
Small doses of neostigmine may promote the recovery of postoperative gastrointestinal function without obvious side effects.
Topics: China; Humans; Neostigmine; Postoperative Nausea and Vomiting
PubMed: 35016456
DOI: 10.21037/apm-21-3291