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1.  Sugammadex for reversal of neuromuscular block after rapid sequence intubation: a systematic review and economic assessment† 
BJA: British Journal of Anaesthesia  2010;105(5):568-575.
Sugammadex 16 mg kg−1 can be used for the immediate reversal of neuromuscular block 3 min after administration of rocuronium and could be used in place of succinylcholine for emergency intubation. We have systematically reviewed the efficacy and cost-effectiveness and made an economic assessment of sugammadex for immediate reversal. The economic assessment investigated whether sugammadex appears cost-effective under various assumptions about the value of any reduction in recovery time with sugammadex, the likelihood of a ‘can't intubate, can't ventilate’ (CICV) event, the age of the patient, and the length of the procedure. Three trials were included in the efficacy review. Sugammadex administered 3 or 5 min after rocuronium produced markedly faster recovery than placebo or spontaneous recovery from succinylcholine-induced block. No published economic evaluations were found. Our economic analyses showed that sugammadex appears more cost-effective, where the value of any reduction in recovery time is greater, where the reduction in mortality compared with succinylcholine is greater, and where the patient is younger, for lower probabilities of a CICV event and for long procedures which do not require profound block throughout. Because of the lack of evidence, the value of some parameters remains unknown, which makes it difficult to provide a definitive assessment of the cost-effectiveness of sugammadex in practice. The use of sugammadex in combination with high-dose rocuronium is efficacious. Further research is needed to clarify key parameters in the analysis and to allow a fuller economic assessment.
PMCID: PMC2955537  PMID: 20937718
complications, intubation tracheal; neuromuscular block, recovery; neuromuscular block, rocuronium; neuromuscular block, succinylcholine
2.  Sugammadex versus neostigmine reversal of moderate rocuronium-induced neuromuscular blockade in Korean patients 
Korean Journal of Anesthesiology  2013;65(6):501-507.
Rapid and complete reversal of neuromuscular blockade (NMB) is desirable at the end of surgery. Sugammadex reverses rocuronium-induced NMB by encapsulation. It is well tolerated in Caucasian patients, providing rapid reversal of moderate (reappearance of T2) rocuronium-induced NMB. We investigated the efficacy and safety of sugammadex versus neostigmine in Korean patients.
This randomized, safety assessor-blinded trial (NCT01050543) included Korean patients undergoing general anesthesia. Rocuronium 0.6 mg/kg was given prior to intubation with maintenance doses of 0.1-0.2 mg/kg as required. Patients received sugammadex 2.0 mg/kg or neostigmine 50 µg/kg with glycopyrrolate 10 µg/kg to reverse the NMB at the reappearance of T2, after the last rocuronium dose. The primary efficacy endpoint was the time from sugammadex or neostigmine administration to recovery of the train-of-four (TOF) ratio to 0.9. The safety of these medications was also assessed.
Of 128 randomized patients, 118 had evaluable data (n = 59 in each group). The geometric mean (95% confidence interval) time to recovery of the TOF ratio to 0.9 was 1.8 (1.6, 2.0) minutes in the sugammadex group and 14.8 (12.4, 17.6) minutes in the neostigmine group (P < 0.0001). Sugammadex was generally well tolerated, with no evidence of residual or recurrence of NMB; four patients in the neostigmine group reported adverse events possibly indicative of inadequate NMB reversal.
Sugammadex was well tolerated and provided rapid reversal of moderate rocuronium-induced NMB in Korean patients, with a recovery time 8.1 times faster than neostigmine. These results are consistent with those reported for Caucasian patients.
PMCID: PMC3888842  PMID: 24427455
Caucasian; Korean; Neostigmine; Neuromuscular blockade; Rocuronium; Sugammadex
3.  Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine.  
BMC Anesthesiology  2010;10:15.
Acetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia.
Patients aged ≥18 years, American Society of Anesthesiologists class 1-4, scheduled to undergo surgery under general anesthesia were enrolled in this phase III, multicenter, randomized, safety-assessor blinded study. Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation, with maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive sugammadex 4 mg/kg or neostigmine 70 μg/kg with glycopyrrolate 14 μg/kg at 1-2 post-tetanic counts. The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9. Safety assessments included physical examination, laboratory data, vital signs, and adverse events.
Eighty three patients were included in the intent-to-treat population (sugammadex, n = 47; neostigmine, n = 36). Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex (4.5 minutes) compared with neostigmine (66.2 minutes; p < 0.0001) (median, 3.3 minutes with sugammadex versus 49.9 minutes with neostigmine). No serious drug-related adverse events occurred in either group.
Recovery from profound vecuronium-induced block is significantly faster with sugammadex, compared with neostigmine. Neostigmine did not rapidly reverse profound neuromuscular block (Trial registration number: NCT00473694).
PMCID: PMC2944304  PMID: 20809967
4.  Sugammadex is effective in reversing rocuronium in the presence of antibiotics 
BMC Anesthesiology  2014;14:69.
The effectiveness of sugammadex in reversing rocuronium-induced neuromuscular blockade (NMB) in the presence of drugs that may potentiate NMB remains to be fully established. The aim of this post-hoc analysis of data from a Phase III clinical trial (VISTA; NCT00298831) was to investigate the impact of antibiotics on recovery from rocuronium-induced NMB after administration of sugammadex for reversal, and compared the neuromuscular recovery in patients who received antibiotics preoperatively with those who did not.
A Phase III, multicenter, open-label study designed to reflect potential use of sugammadex in clinical practice was conducted at 19 sites. Data obtained from patients who received antibiotics were compared with the cohort of patients who underwent the same protocol without antibiotics. Each subject received rocuronium 0.6 mg/kg for muscle relaxation, after which tracheal intubation was performed; patients were also permitted to receive maintenance doses of rocuronium 0.15 mg/kg to maintain the desired level of NMB throughout the operation, as required.. At least 15 min after the last rocuronium dose, patients received sugammadex 4.0 mg/kg for reversal. Neuromuscular monitoring was continued until a train-of-four (TOF) ratio of ≥0.9 was achieved or the anesthetic was discontinued.
The presence of antibiotics prior to the administration of sugammadex did not affect the recovery time from rocuronium-induced NMB when sugammadex 4.0 mg/kg was administered at least 15 min after the last dose of rocuronium. In the presence of antibiotics, the geometric mean (95% CI) time from administration of sugammadex 4.0 mg/kg to recovery of the TOF ratio to ≥0.9 was 1.6 (1.4–1.9) min (range: 0.7–10.5 min), compared with 2.0 (1.8–2.3) min (range: 0.7–22.3 min) for patients who did not receive antibiotics.
These findings suggest that prophylactic antibiotic use is unlikely to have a major impact on the recovery time from rocuronium-induced NMB with sugammadex reversal.
Trial registration Identifier: NCT00298831.
PMCID: PMC4142447  PMID: 25157214
Sugammadex; Rocuronium; Neuromuscular blockade; Antibiotics
5.  Rocuronium blockade reversal with sugammadex vs. neostigmine: randomized study in Chinese and Caucasian subjects 
BMC Anesthesiology  2014;14:53.
This study compared efficacy and safety of the selective relaxant binding agent sugammadex (2 mg/kg) with neostigmine (50 μg/kg) for neuromuscular blockade (NMB) reversal in Chinese and Caucasian subjects.
This was a randomized, active-controlled, multicenter, safety-assessor-blinded study (NCT00825812) in American Society of Anesthesiologists Class 1-3 subjects undergoing surgery with propofol anesthesia. Rocuronium 0.6 mg/kg was administered for endotracheal intubation, with 0.1–0.2 mg/kg maintenance doses given as required. NMB was monitored using TOF-Watch® SX. At second twitch reappearance, after last rocuronium dose, subjects received sugammadex 2 mg/kg or neostigmine 50 μg/kg plus atropine 10–20 μg/kg, according to randomization. Primary efficacy variable was time from sugammadex/neostigmine to recovery of the train-of-four (TOF) ratio to 0.9.
Overall, 230 Chinese subjects (sugammadex, n = 119, neostigmine, n = 111); and 59 Caucasian subjects (sugammadex, n = 29, neostigmine, n = 30) had evaluable data. Geometric mean (95% CI) time to recovery to TOF ratio 0.9 was 1.6 (1.5–1.7) min with sugammadex vs 9.1 (8.0–10.3) min with neostigmine in Chinese subjects. Corresponding times for Caucasian subjects were 1.4 (1.3–1.5) min and 6.7 (5.5–8.0) min, respectively. Sugammadex 2 mg/kg was generally well tolerated, with no serious adverse events reported. There was no residual NMB or recurrence of NMB.
Both Chinese and Caucasian subjects recovered from NMB significantly faster after sugammadex 2 mg/kg vs neostigmine 50 μg/kg, with a ~5.7 times (p < 0.0001) faster recovery with sugammadex vs neostigmine in Chinese subjects. Sugammadex was generally well tolerated.
Trial registration Identifier: NCT00825812.
PMCID: PMC4153006  PMID: 25187755
Sugammadex; Rocuronium; Neostigmine; Neuromuscular blockade; Chinese; Caucasian
6.  Comparison of reversal and adverse effects of sugammadex and combination of — Anticholinergic-Anticholinesterase agents in pediatric patients 
We aimed to compare clinical effects of sugammadex versus combination of anticholinergic-anticholinesterase agents for reversing of nondepolarizing neuromuscular block in pediatric patients.
Materials and Methods:
A total of 60 pediatric patients whom should be performed general anesthesia in the supine position were enrolled to this randomized double-blinded clinical trial. Fentanyl 1 μg/kg, propofol 2 mg/kg, rocuronium 0.6 mg/kg were used in induction and sevofluran, 50% O2-50% N2O in maintenance of anesthesia. Neuromuscular conductions were assessed by train of four (TOF)-Watch SX (Organon, Schering-Plough, Ireland) acceleromyograph. Patients were intubated at the moment of TOF 0. At the end of the operation emergence of T2 point was replied by 2 mg/kg sugammadex administration in group 1 and 0.06 mg/kg neostigmine +0.02 mg/kg atropine in group 2. At the moment of T0.9 inhalation, gases were ceased, and patients were extubated. Hemodynamic alterations, access to T0.9, extubation time, recovery parameters, drug consumptions and adverse effects were recorded.
Train of four scores showed a lesser increase in group 2 than group 1 from 15th s to 30th min during post reverse period (from 6.9 ± 6.4 to 91.7 ± 7.2 in group 2 vs. from 35.4 ± 21.4 to 99.5 ± 1.0 in group 1) (p < 0.0004). Group 1 patients exhibited much more complete muscle strength rates than group 2 (P < 0.001). T0.9 and extubation times were significantly longer in group 2 than group 1 (P < 0.001). Comparison of adverse effects yielded no difference.
Sugammadex can be considered as a safe agent in order to reverse neuromuscular block in pediatric patients.
PMCID: PMC4235098  PMID: 25422663
Atropine; gamma cyclodextrins; neostigmine; neuromuscular nondepolarizing agents
7.  A Miracle That Accelerates Operating Room Functionality: Sugammadex 
BioMed Research International  2014;2014:945310.
Background. Sugammadex offers a good alternative to the conventional decurarisation process currently performed with cholinesterase inhibitors. Sugammadex, which was developed specifically for the aminosteroid-structured rocuronium and vecuronium neuromuscular blockers, is a modified cyclodextrin made up of 8 glucose monomers arranged in a cylindrical shape. Methods. In this study, the goal was to investigate the efficacy of sugammadex. Sugammadex was used when there was insufficient decurarisation following neostigmine. This study was performed on 14 patients who experienced insufficient decurarisation (TOF <0.9) with neostigmine after general anaesthesia in the operating rooms of a university and a state hospital between June, 2012, and January, 2014. A dose of 2 mg/kg of sugammadex was administered. Results. Time elapsed until sugammadex administration following neostigmine 37 ± 6 min, following sugammadex it took 2.1 ± 0.9 min to reach TOF ≥0.9, and the extubation time was 3.2 ± 1.4 min. No statistically significant differences were detected in the hemodynamic parameters before and after sugammadex application. From the time of administration of sugammadex to the second postoperative hour, no side effects or complications occurred. None of the patients experienced acute respiratory failure or residual block during this time period. Conclusion. Sugammadex was successfully used to reverse rocuronium-induced neuromuscular block in patients where neostigmine was insufficient.
PMCID: PMC4150404  PMID: 25202709
8.  Sugammadex: A revolutionary drug in neuromuscular pharmacology 
Sugammadex (ORG 25969) is a unique neuromuscular reversal drug; a novel cyclodextrin, the first in a new class of selective relaxant binding agents, which reverse neuromuscular blockade (NMB) with the aminosteroid non-depolarizing muscle relaxants rocuronium and vecuronium. Sugammadex can reverse moderate or deep NMB. The clinical use of sugammadex promises to eliminate many of the shortcomings in current anesthetic practice with regard to antagonism of rocuronium and other aminosteroid muscle relaxants.
PMCID: PMC4173552
Encapsulation; residual paralysis; rocuronium; selective relaxant binding agent; sugammadex
9.  The use of 3 sugammadex out of 5 reversal of during recovery of rocuronium-induced neuromuscular blockade in a patient with post-tonsillectomy hemorrhage: a case report 
Post-tonsillectomy hemorrhage (PTH) is the most frequent complication of tonsillectomy, and occasionally results in a lethal outcome. A 21-year-old man (height 180 cm, weight 95 kg) was scheduled for a bilateral tonsillectomy and uvulopalatopharyngoplasty for treatment of obstructive sleep apnea. He required 5 rounds of general anesthesia due to recurrent PTH. The anesthesiologist used sugammadex a total of 3 times to achieve the successful reversal of the deep neuromuscular blockade (NMB) induced by rocuronium. After sugammadex 2 mg/kg was administered, the NMB was reversed in 2 minutes each time. Re-administration of rocuronium within a short time interval after sugammadex may result in unpredictable effects of neuromuscular blocking agents. Sugammadex made it possible to perform a rapid, complete reverse when the residual block was maintained by an incomplete reversal of anticholinesterase.
PMCID: PMC4121494  PMID: 25097738
Postoperative hemorrhage; Rocuronium; Sugammadex; Tonsillectomy
10.  Sugammadex as a reversal agent for neuromuscular block: an evidence-based review 
Core Evidence  2013;8:57-67.
Sugammadex is the first clinical representative of a new class of drugs called selective relaxant binding agents. It has revolutionized the way anesthesiologists think about drug reversal. Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action. Due to its 1:1 binding of rocuronium or vecuronium, it is able to reverse any depth of neuromuscular block. So far, it has been approved for use in adult patients and for pediatric patients over 2 years. Since its approval in Europe, Japan, and Australia, further insight on its use in special patient populations and specific diseases have become available. Due to its pharmacodynamic profile, sugammadex, in combination with rocuronium, may have the potential to displace succinylcholine as the “gold standard” muscle relaxant for rapid sequence induction. The use of rocuronium or vecuronium, with the potential of reverse of their action with sugammadex, seems to be safe in patients with impaired neuromuscular transmission, ie, neuromuscular diseases, including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence suggesting an economic advantage of using sugammadex and justifying its relatively high cost for an anesthesia-related drug, is missing.
PMCID: PMC3789633  PMID: 24098155
reversal agent; cyclodextrin; PORC; SRBAs
11.  Sugammadex and Ideal Body Weight in Bariatric Surgery 
Background. The obese patients have differences in body composition, drug distribution, and metabolism. Sugammadex at T2 recovery in a dose of 2 mg kg−1 of real body weight (RBW) can completely reverse the NMB block; in our study we investigated the safety and efficacy of Sugammadex dose based on their ideal body weight (IBW). Methods. 40 patients of both sexes undergoing laparoscopic bariatric surgery were enrolled divided into 2 groups according to the dose of Sugammadex: the first received a dose of 2 mg kg−1 of IBW and the second received a dose of 2 mg kg−1 of RBW. Both were anesthetized with doses calculated according to the IBW: fentanyl 2 μg kg−1, propofol 3 mg kg−1, rocuronium 0,6 mg kg−1, oxygen, air, and desflurane (6–8%). Maintenance doses of rocuronium were 1/4 of the intubation dose. Sugammadex was administrated at T2 recovery. Results. The durations of intubation and maintenance doses of rocuronium were similar in both groups. In IBW group, the T4/T1 value of 0.9 was reached in 151 ± 44 seconds and in 121 ± 55 seconds in RBW group (P = 0.07). Discussion. Recovery times to T4/T1 of 0.9 are surprisingly similar in both groups without observing any postoperative residual curarization. Conclusion. Sugammadex doses calculated according to the IBW are certainly safe for a rapid recovery and absence of PORC.
PMCID: PMC3690214  PMID: 23840203
12.  Sugammadex: clinical development and practical use 
Korean Journal of Anesthesiology  2013;65(6):495-500.
Sugammadex is belonging to a new class of drugs: the selective relaxant binding agents. Sugammadex can reverse residual paralysis by encapsulating free circulating non depolarizing muscle relaxants. The mains advantages of sugammadex when compared with conventional anticholinesterase agents are a much faster recovery time and the unique ability, for the first time, to reverse rapidly and efficiently deep levels of neuromuscular blockade. However it only works for reversal of rocuronium or vecuronium-induced neuromuscular blockade. When administered 3 min after rocuronium the use of a large dose (16 mg/kg) can even reverse rocuronium significantly faster than the spontaneous recovery after succinylcholine.
PMCID: PMC3888841  PMID: 24427454
Cyclodextrins; Neostigmine; Neuromuscular block; Residual neuromuscular blockade; Rocuronium; Sugammadex
13.  Sensitivity to Rocuronium-Induced Neuromuscular Block and Reversibility with Sugammadex in a Patient with Myotonic Dystrophy 
Case Reports in Anesthesiology  2012;2012:107952.
We report a patient with myotonic dystrophy who showed prolonged rocuronium-induced neuromuscular blockade, although with a fast recovery with sugammadex. During general anesthesia with propofol and remifentanil, the times to spontaneous recovery of the first twitch (T1) of train of four to 10% of control values after an intubating dose of rocuronium 1 mg/kg and an additional dose of 0.2 mg/kg were 112 min and 62 min, respectively. Despite the high sensitivity to rocuronium, sugammadex 2 mg/kg administered at a T1 of 10% safely and effectively antagonized rocuronium-induced neuromuscular block in 90 s.
PMCID: PMC3350161  PMID: 22606401
14.  A temporary decrease in twitch response following reversal of rocuronium-induced neuromuscular block with a small dose of sugammadex in a pediatric patient 
Journal of Anesthesia  2013;28(2):288-290.
We report a temporary decrease in twitch response following reversal of rocuronium-induced neuromuscular block with a small dose of sugammadex in our dose-finding study in pediatric patients. A 19-month-old female infant (9.6 kg, 80 cm) was scheduled for elective cheiloplasty surgery. Anesthesia was induced with nitrous oxide 50 % and sevoflurane 5 % and maintained with air, oxygen, sevoflurane 3 %, and fentanyl (total, 3 μg/kg). Neuromuscular monitoring was performed at the adductor pollicis muscle after induction of anesthesia but before the administration of rocuronium. Total dose of rocuronium during the surgery was 0.9 mg/kg. Neuromuscular block was reversed with 0.5 mg/kg sugammadex when one response was observed with post-tetanic count stimulation. Twitch responses after sugammadex administration showed a temporary decrease after its initial recovery. Maximum decreases in twitch responses were observed 17 min after initial dose of sugammadex. Twitch responses recovered to their control values after additional doses of 3.5 mg/kg sugammadex (4 mg/kg in total). Time from sugammadex administration to maximum decreases in twitch responses is earlier than has been reported in adults (20–70 min). It is demonstrated that following neuromuscular block reversal with insufficient dose of sugammadex, there is a possibility of the recurrence of residual paralysis within less than 20 min in pediatric patients.
PMCID: PMC3983881  PMID: 23963464
Sugammadex; Rocuronium; Pediatric; Neuromuscular monitoring
15.  Update on the management of neuromuscular block: focus on sugammadex 
Steroidal neuromuscular blocking agents (NMBAs), such as rocuronium, are widely used in clinical anesthesia and emergency medicine to facilitate endotracheal intubation and artificial ventilation and to allow surgical access to body cavities. Reversal of neuromuscular blockade is important for the acceleration of patient recovery and prevention of postoperative residual neuromuscular blockade and reduces the incidence of severe morbidity and mortality associated with anesthesia management. Sugammadex is the first selective relaxant binding agent (SRBA) and has been designed to reverse the steroidal neuromuscular blocking drug rocuronium. Encapsulation of the rocuronium molecule by sugammadex results in a rapid decrease in free rocuronium in the plasma and subsequently at the nicotinic receptor at the motor endplate. After encapsulation, rocuronium is not available to bind to the nicotinic receptor in the neuromuscular junction. This promotes the liberation of acetylcholine receptors, and muscle activity reappears. This new concept of reversal of neuromuscular block induced by rocuronium (or vecuronium) led to impressive results in animal and phase 1 and 2 studies. Sugammadex is currently in phase 3 clinical studies and may be commercially available by 2008.
PMCID: PMC2656290  PMID: 19300584
neuromuscular block; rocuronium; neuromuscular blocking agent; sugammadex; reversal agent
16.  Biological evaluation of the effect of sugammadex on hemostasis and bleeding 
Notification of sugammadex has been supplemented with a section on hemostasis, including a longer clotting time in the first minutes following injection, without any documented clinical consequences. The objective of this observational study was to analyze the effects of sugammadex administration on routine coagulation tests and bleeding in the clinical setting.
After Institutional Review Board approval, a prospective observational study was conducted between January and December 2011. Adult patients scheduled for laparotomies were analyzed in groups according to the type of reversal (without sugammadex versus 2 or 4 mg/kg sugammadex). There were no changes in our current clinical practice. Blood samples drawn from these patients were standardized at the same time and tested using the same daily calibrated machine. The endpoint was a comparison of the activated partial thromboplastin time (aPTT), prothrombin time (PT), hemoglobin (Hb) level and hematocrit (Ht), immediately before sugammadex administration (H0) and 1 h after neuromuscular block reversal (H1).
One hundred and forty-two patients in three groups were included as follows: 11 in the "without sugammadex" group, 64 in the "2 mg/kg sugammadex" group and 67 in the "4 mg/kg sugammadex" group. Results did not differ significantly among the groups.
In this prospective observational study, the use of 2 and 4 mg/kg sugammadex was not associated with a longer clotting time or decreased hemoglobin concentrations. Future prospective investigations should study patients receiving 16 mg/kg sugammadex and/or with abnormal coagulation tests.
PMCID: PMC4318859  PMID: 25664150
Activated partial thromboplastin time; Hemostasis; Prothrombin time; Sugammadex
17.  In the hour of Sugammadex 
Sugammadex is a modified gamma-cyclodextrin which is showing favorable outcomes regarding reversal of neuromuscular blockade, especially by rocuronium. It is designed to encapsulate rocuronium and being considered a new class of drugs as selective relaxant binding agents. It has given countless benefits to the patients at risk of incomplete or delayed recovery after neuromuscular block and has renown for another milestone in anesthesia practice. Recurrence of neuromuscular block has not been reported to be associated with the provided doses of sugammadex that are adequate for selected for reversal. Acceptable profiles are brought to light telling safety of sugammadex. However, some questions related to the twitch characteristics those resembled succinylcholine when reversal, the application for rocuronium anaphylaxis, and the hypersensitivity or anaphylaxis to sugammadex remain and are need of further investigation. It is imperative that potential problems that we need attention may include the patient's history of pulmonary disease and allergic disease for using sugammadex.
PMCID: PMC3558646  PMID: 23372878
Allergy; Hypersensitivity; Neuromuscular blockade; Patient safety; Sugammadex
18.  Sugammadex rescue following prolonged rocuronium neuromuscular blockade with ‘recurarisation’ in a patient with severe renal failure  
BMJ Case Reports  2013;2013:bcr2012007603.
We describe our experience of a 71-year-old patient with severe renal failure, who exhibited an unusually prolonged rocuronium-induced neuromuscular blockade (>4 h) and apparent recurarisation, following emergency rapid sequence induction (RSI). At the end of operation, 45 min post induction, train-of-four (TOF) testing had been 4/4 prior to wake up. No respiratory effort was seen 150 min postinduction, despite further neostigmine/glycopyrrolate and repeat TOF 4/4. The patient was resedated and transferred to the intensive care unit (ICU). At 180 min postinduction, fade was evident on TOF, suggestive of rocuronium reblockade. At 285 min, the patient was extubated safely following sugammadex administration and discharged uneventfully from the ICU. An important lesson to recognise is the potential for extremely prolonged neuromuscular blockade following rocuronium in patients with severe renal failure, particularly when using the higher doses (1.2 mg/kg) required for RSI, and that TOF in such cases may not be reliable in detecting residual blockade.
PMCID: PMC3604464  PMID: 23396837
19.  Introduction of sugammadex as standard reversal agent: Impact on the incidence of residual neuromuscular blockade and postoperative patient outcome 
Indian Journal of Anaesthesia  2013;57(1):46-51.
The aim of this prospective audit was to investigate clinical practice related to muscle relaxant reversal and the impact made by the recent introduction of sugammadex on patient outcome at a tertiary teaching hospital.
Data from all patients intubated at our institution during two epochs of seven consecutive days each was collected prospectively. Directly prior to extubation, the train-of-four (TOF) ratio was assessed quantitatively by an independent observer. Postoperative outcome parameters were complications in the recovery room and radiological diagnosed atelectasis or pneumonia within 30 days.
Data from 146 patients were analysed. Three reversal strategies were used: no reversal, neostigmine or sugammadex. The TOF ratio was less than 0.7 in 17 patients (nine no reversal, eight neostigmine) and less than 0.9 in 47 patients (24 no reversal, 19 neostigmine, four sugammadex). Those reversed with sugammadex showed fewer episodes of postoperative oxygen desaturation (15% vs. 33%; P<0.05). TOF ratios of less than 0.7 (P<0.05) and also <0.9 (P<0.01) were more likely associated with X-ray results consistent with postoperative atelectasis or pneumonia.
Our results suggest a significant impact of residual paralysis on patient outcome. The use of sugammadex resulted in the lowest incidence of residual paralysis.
PMCID: PMC3658335  PMID: 23716766
Neostigmine; residual paralysis; sugammadex
20.  Sugammadex, a Neuromuscular Blockade Reversal Agent, Causes Neuronal Apoptosis in Primary Cultures 
Sugammadex, a γ-cyclodextrin that encapsulates selectively steroidal neuromuscular blocking agents, such as rocuronium or vecuronium, has changed the face of clinical neuromuscular pharmacology. Sugammadex allows a rapid reversal of muscle paralysis. Sugammadex appears to be safe and well tolerated. Its blood-brain barrier penetration is poor (< 3% in rats), and thus no relevant central nervous toxicity is expected. However the blood brain barrier permeability can be altered under different conditions (i.e. neurodegenerative diseases, trauma, ischemia, infections, or immature nervous system).
Using MTT, confocal microscopy, caspase-3 activity, cholesterol quantification and Western-blot we determine toxicity of Sugammadex in neurons in primary culture. Here we show that clinically relevant sugammadex concentrations cause apoptotic/necrosis neuron death in primary cultures. Studies on the underlying mechanism revealed that sugammadex-induced activation of mitochondria-dependent apoptosis associates with depletion of neuronal cholesterol levels. Furthermore SUG increase CytC, AIF, Smac/Diablo and CASP-3 protein expression in cells in culture. Potential association of SUG-induced alteration in cholesterol homeostasis with oxidative stress and apoptosis activation occurs. Furthermore, resistance/sensitivity to oxidative stress differs between neuronal cell types.
PMCID: PMC3752716  PMID: 23983586
Sugammadex; apoptosis; CytC; AIF; Smac/Diablo and CASP-3.
21.  Discovery, development, and clinical application of sugammadex sodium, a selective relaxant binding agent 
Neuromuscular blockade, induced by neuromuscular blocking agents, has allowed prescribed immobility, improved surgical exposure, optimal airway management conditions, and facilitated mechanical ventilation. However, termination of the effects of neuromuscular blocking agents has, until now, remained limited. A novel cyclodextrin encapsulation process offers improved termination of the paralytic effects of aminosteroidal non-depolarizing neuromuscular blocking agents. Sugammadex sodium is the first in a new class of drug called selective relaxant binding agents. Currently, in clinical trials, sugammadex, a modified gamma cyclodextrin, has shown consistent and rapid termination of neuromuscular blockade with few side effects. The pharmacology of cyclodextrins in general and sugammadex in particular, together with the results of current clinical research are reviewed. The ability of sugammadex to terminate the action of neuromuscular blocking agents by direct encapsulation is compared to the indirect competitive antagonism of their effects by cholinesterase inhibitors. Also discussed are the clinical implications that extend beyond fast, effective reversal, including numerous potential perioperative benefits.
PMCID: PMC2761174  PMID: 19920893
modified cyclodextrin; selective relaxant binding agent (SRBA); sugammadex; encapsulation; muscle relaxants; neuromuscular blockade reversal
22.  Sugammadex and Reversal of Neuromuscular Block in Adult Patient with Duchenne Muscular Dystrophy 
Case Reports in Anesthesiology  2014;2014:680568.
Duchenne's muscular dystrophy (DMD) is the most common and severe form of myopathy. Patients with DMD are more sensitive to sedative, anesthetic, and neuromuscular blocking agents which may result in intraoperative and early postoperative cardiovascular and respiratory complications, as well as prolonged recovery from anesthesia. In this case report, we describe a 25-year-old male patient admitted for cholecystectomy under general anesthesia. We induced our anesthesia by oxygen, propofol, fentanyl, and rocuronium bromide. Maintenance was done by fentanyl, rocuronium bromide, sevoflurane, and O2. We report in this case the safety use of sugammadex to antagonize the neuromuscular block and rapid recovery in such category of patients.
PMCID: PMC3970074  PMID: 24715988
23.  The use of sugammadex in a patient with Kennedy's disease under general anesthesia 
Saudi Journal of Anaesthesia  2014;8(3):418-420.
Kennedy's disease (KD), also known as spinal and bulbar muscular atrophy, is a rare, X-linked recessive, neurodegenerative disorder of the lower motor neurons characterized by progressive bulbar and appendicle muscular atrophy. Here we report a case of a 62-year-old male patient with KD, weighing 70 kg and 173 cm tall, was scheduled for frontal sinusectomy due to sinusitis. General anesthesia was induced through propofol 80 mg, remifentanil 0.25 μg/kg/min and 40 mg rocuronium. We were successfully able to use a sugammadex on a patient suffering from KD in order to reverse rocuronium-induced neuromuscular blockade.
PMCID: PMC4141401  PMID: 25191203
Kennedy's disease; sugammadex; general anesthesia
24.  Negative Pressure Pulmonary Edema after Reversing Rocuronium-Induced Neuromuscular Blockade by Sugammadex 
Case Reports in Anesthesiology  2014;2014:135032.
Negative pressure pulmonary edema (NPPE) is a rare complication that accompanies general anesthesia, especially after extubation. We experienced a case of negative pressure pulmonary edema after tracheal extubation following reversal of rocuronium-induced neuromuscular blockade by sugammadex. In this case, the contribution of residual muscular block on the upper airway muscle as well as large inspiratory forces created by the respiratory muscle which has a low response to muscle relaxants, is suspected as the cause.
PMCID: PMC3970085  PMID: 24715986
25.  Anaesthetic management of a patient with myasthenia gravis for abdominal surgery using sugammadex 
We report a case of a patient with tumor of the caecum with coexistent myasthenia gravis (a form according to Osserman II A), requiring general anesthesia for abdominal surgery. To reverse the neuromuscular block induced by vecuronium was used sugammadex.
PMCID: PMC3258733  PMID: 22291783
sugammadex; myasthenia gravis; neuromuscular monitoring; vecuronium

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