Reversal of Rocuronium-induced (1.2 mg/kg) Profound Neuromuscular Block by Sugammadex

Background Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified gamma-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular blockade at 5 min in American Society of Anesthesiologists physical status I and II patients. Methods Forty-five American Society of Anesthesiologists physical status I and II patients (aged 18-64 yr) scheduled to undergo surgical procedures (anticipated anesthesia duration >/= 90 min) were randomly assigned to a phase II, multicenter, assessor-blinded, placebo-controlled, parallel, dose-finding study. Anesthesia was induced and maintained with propofol and an opioid. Profound neuromuscular blockade was induced with 1.2 mg/kg rocuronium bromide. Sugammadex (2.0, 4.0, 8.0, 12.0, or 16.0 mg/kg) or placebo (0.9% saline) was then administered 5 min after the administration of rocuronium. Neuromuscular function was monitored by acceleromyography, using train-of-four nerve stimulation. Recovery time was the time from the start of administration of sugammadex or placebo, to recovery of the train-of-four ratio to 0.9. Safety assessments were performed on the day of the operation and during the postoperative and follow-up period. Results A total of 43 patients received either sugammadex or placebo. Increasing doses of sugammadex reduced the mean recovery time from 122 min (spontaneous recovery) to less than 2 min in a dose-dependent manner. Signs of recurrence of blockade were not observed. No serious adverse events related to sugammadex were reported. Two adverse events possibly related to sugammadex were reported in two patients (diarrhea and light anesthesia); however, both patients recovered without sequelae. Conclusions Sugammadex rapidly and effectively reversed profound rocuronium-induced neuromuscular blockade in humans and was well tolerated.

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Reversal of Profound Neuromuscular Block by Sugammadex Administered Three Minutes after Rocuronium

Anesthesiology ◽

10.1097/aln.0b013e31819dabb0 ◽

2009 ◽

Vol 110 (5) ◽

pp. 1020-1025 ◽

Cited By ~ 154

Author(s):

Chingmuh Lee ◽

Jonathan S. Jahr ◽

Keith A. Candiotti ◽

Brian Warriner ◽

Mark H. Zornow ◽

...

Keyword(s):

Spontaneous Recovery ◽

Neuromuscular Block ◽

High Dose ◽

Serious Adverse Events ◽

Duration Of Action ◽

Parallel Group ◽

Train Of Four ◽

American Society ◽

American Society Of Anesthesiologists ◽

Mean Time

Background Rocuronium in intubation doses provides similar intubation conditions as succinylcholine, but has a longer duration of action. This study compared time to sugammadex reversal of profound rocuronium-induced neuromuscular block with time to spontaneous recovery from succinylcholine. Methods One hundred and fifteen adult American Society of Anesthesiologists Class I-II surgical patients were randomized to this multicenter, safety-assessor-blinded, parallel group, active-controlled, Phase IIIa trial. Anesthesia was induced and maintained with propofol and an opioid. Neuromuscular transmission was blocked and tracheal intubation facilitated with 1.2 mg/kg rocuronium or 1 mg/kg succinylcholine. Sugammadex (16 mg/kg) was administered 3 min after rocuronium administration. Neuromuscular function was monitored by acceleromyography. The primary efficacy endpoint was the time from the start of relaxant administration to recovery of the first train-of-four twitch (T(1)) to 10%. Results One hundred and ten patients received study treatment. Mean times to recovery of (T(1)) to 10% and (T(1)) to 90% were significantly faster in the rocuronium-sugammadex group (4.4 and 6.2 min, respectively), as compared with the succinylcholine group (7.1 and 10.9 min, respectively; all P < 0.001). Timed from sugammadex administration, the mean time to recovery of (T(1)) to 10%, (T(1)) to 90%, and the train-of-four (T(4)/T(1)) ratio to 0.9 was 1.2, 2.9, and 2.2 min, respectively. Reoccurrence of the block was not observed. There were no serious adverse events related to study treatments. Conclusion Reversal of profound high-dose rocuronium-induced neuromuscular block (1.2 mg/kg) with 16 mg/kg sugammadex was significantly faster than spontaneous recovery from 1 mg/kg succinylcholine.

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Comparison of Train of Four Measurements with Kinemyography NMT DATEX and Accelerography TOFscan

Medical Sciences ◽

10.3390/medsci9020021 ◽

2021 ◽

Vol 9 (2) ◽

pp. 21

Author(s):

Cyrus Motamed ◽

Migena Demiri ◽

Nora Colegrave

Keyword(s):

Neuromuscular Blockade ◽

Lower Limit ◽

Elective Surgery ◽

Orotracheal Intubation ◽

Neuromuscular Blocking ◽

Physical Status Classification ◽

Train Of Four ◽

Surgery First ◽

American Society ◽

American Society Of Anesthesiologists

Introduction: This study was designed to compare the Datex neuromuscular transmission (NMT) kinemyography (NMTK) device with the TOFscan (TS) accelerometer during the onset and recovery of neuromuscular blockade. Patients and methods: This prospective study included adult patients who were scheduled to undergo elective surgery with general anesthesia and orotracheal intubation. The TS accelerometer was randomly placed at the adductor pollicis on one hand, and the NMTK was placed on the opposite arm. Anesthesia was initiated with remifentanil target-controlled infusion (TCI) and 2.0–3.0 mg/kg of propofol. Thereafter, 0.5 mg/kg of atracurium or 0.6 mg/kg of rocuronium was injected. If needed, additional neuromuscular blocking agents were administered to facilitate surgery. First, we recorded the train of four (TOF) response at the onset of neuromuscular blockade to reach a TOF count of 0. Second, we recorded the TOF response at the recovery of neuromuscular blockade to obtain a T4/T1 90% by both TS and NMTK. Results: There were 32 patients, aged 38–83 years, with the American Society of Anesthesiologists (ASA) Physical Status Classification I–III included and analyzed. Surgery was abdominal, gynecologic, or head and neck. The Bland and Altman analysis for obtaining zero responses during the onset showed a bias (mean) of 2.7 s (delay) of TS in comparison to NMTK, with an upper/lower limit of agreement of [104; −109 s] and a bias of 36 s of TS in comparison to NMTK, with an upper/lower limit of agreement of [−21.8, −23.1 min] during recovery (T4/T1 > 90%). Conclusions: Under the conditions of the present study, the two devices are not interchangeable. Clinical decisions for deep neuromuscular blockade should be made cautiously, as both devices appear less accurate with significant variability.

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Neuromuscular blockade effects of cisatracurium in 11 cats undergoing ophthalmological surgery anaesthetised with isoflurane

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x211021829 ◽

2021 ◽

pp. 1098612X2110218

Author(s):

Anne-Sophie Van Wijnsberghe ◽

Keila K Ida ◽

Petra Dmitrovic ◽

Alexandru Tutunaru ◽

Charlotte Sandersen

Keyword(s):

Neuromuscular Blockade ◽

Case Series ◽

Neuromuscular Function ◽

Duration Of Action ◽

Cardiovascular Side Effects ◽

Train Of Four ◽

Physical Classification ◽

The Mean ◽

American Society ◽

American Society Of Anesthesiologists

Case series summary This case series describes the neuromuscular blockade (NMB) following 0.15 mg/kg intravenous (IV) cisatracurium administration in 11 cats undergoing ophthalmological surgery and anaesthetised with isoflurane. Anaesthetic records were analysed retrospectively. Neuromuscular function was assessed by a calibrated train-of-four (TOF) monitor. Cats were 73 ± 53 months old, weighed 4 ± 1 kg and were of American Society of Anesthesiologists’ physical classification 2. Duration of anaesthesia and surgery were 144 ± 27 and 94 ± 24 mins, respectively. The lowest TOF count was zero in four cats, four in six cats and for one cat the TOF ratio never decreased below 31%. The time of onset was between 1 and 6 mins after the administration of cisatracurium and the mean duration of action was 20.4 ± 10.1 mins. Relevance and novel information Cisatracurium at a dose of 0.15 mg/kg IV did not consistently induce a TOF count of zero in all cats. The dose used in these cats did not produce any remarkable cardiovascular side effects. Although the NMB was not complete, the dose given was sufficient to produce central eyeball position, which was the goal of the ophthalmic surgeries.

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Reversal of Meeting Abstracts by Sugammadex after Continuous Infusion of Rocuronium in Patients Randomized to Sevoflurane or Propofol Maintenance Anesthesia

Anesthesiology ◽

10.1097/aln.0b013e3181a51cb0 ◽

2009 ◽

Vol 111 (1) ◽

pp. 30-35 ◽

Cited By ~ 36

Author(s):

Christopher Rex ◽

Stefanie Wagner ◽

Claudia Spies ◽

Jens Scholz ◽

Henk Rietbergen ◽

...

Keyword(s):

Single Dose ◽

Continuous Infusion ◽

Neuromuscular Blockade ◽

Recovery Time ◽

Clinical Effect ◽

Parallel Group ◽

Median Plasma ◽

Train Of Four ◽

American Society ◽

Posttetanic Count

Background Sugammadex rapidly reverses neuromuscular blockade induced by bolus rocuronium doses, but it has not been investigated after continuous rocuronium infusion in surgical patients. We therefore examined the clinical effect of sugammadex for neuromuscular blockade induced by continuous rocuronium infusion in adults undergoing surgery under maintenance anesthesia with sevoflurane or propofol. Methods This four-center, comparative, parallel-group study, randomly assigned 52 adult patients (American Society of Anesthesiologists Class I-III) to maintenance anesthesia with sevoflurane or propofol. Neuromuscular blockade was induced by bolus injection of 0.6 mg/kg rocuronium followed by continuous infusion of 7 microg x kg(-1) x min(-1) rocuronium adjusted to maintain a neuromuscular blockade depth of zero response to train-of-four and a posttetanic count of no more than 10 responses. A single dose of 4 mg/kg sugammadex was administered at first twitch (T1) 3-10%. The primary clinical effect variable was recovery time to a train-of-four ratio of 0.9. Results Median recovery time from start of sugammadex administration to a train-of-four ratio of 0.9 in the sevoflurane and propofol groups was 1.3 and 1.2 min, respectively. The estimated difference in recovery time between groups was 9 s (95% confidence interval -6 to 20 s), entirely within the predefined equivalence interval. Median plasma rocuronium concentration just before sugammadex administration was 33% lower during maintenance anesthesia with sevoflurane than with propofol. Sugammadex was well tolerated. One adverse event (procedural hypotension) was considered to be probably related to sugammadex. Conclusions Single-dose sugammadex (4 mg/kg) after continuous rocuronium infusion is equally effective and well tolerated during maintenance anesthesia with sevoflurane or propofol.

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Comparison of Ketamine and Propofol-Based Regimens for Deep Sedation in Children Undergoing Esophagogastroduodenoscopy

Journal of Pediatric Intensive Care ◽

10.1055/s-0040-1721657 ◽

2020 ◽

Author(s):

Olugbenga Akingbola ◽

Sudesh K. Srivastav ◽

Michelle Nguyen ◽

Dinesh Singh ◽

Edwin M Frieberg ◽

...

Keyword(s):

Adverse Events ◽

Skin Rash ◽

Recovery Time ◽

Deep Sedation ◽

Physical Status ◽

Onset Of Action ◽

American Society

AbstractWe retrospectively reviewed the charts of 180 children sedated for esophagogastroduodenoscopy (EGD) with ketamine or propofol-based regimens at our institution. Pre-EGD diagnoses and American Society of Anesthesiology physical status were similar in all subjects. Onset of action and recovery time for both regimens were not statistically significant (p > 0.05). Mean onset of sedation for all patients was 3.85 ± 3.04 minutes, mean Aldrete score was 6.31 ± 0.61, and mean recovery time was 51.85 ± 31.78 minutes (p > 0.05). Sedation-related adverse events observed include apnea, hypoxemia, bradycardia, hypotension, laryngospasm, skin rash, and wheezing. Deep sedation for pediatric EGD is safe if patients are carefully screened and properly monitored

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A Multicenter Clinical Study of the Safety and Activity of Maleimide-Polyethylene Glycol–modified Hemoglobin (Hemospan®) in Patients Undergoing Major Orthopedic Surgery

Anesthesiology ◽

10.1097/00000542-200612000-00015 ◽

2006 ◽

Vol 105 (6) ◽

pp. 1153-1163 ◽

Cited By ~ 66

Author(s):

Christina Olofsson ◽

Torbjörn Ahl ◽

Torsten Johansson ◽

Sune Larsson ◽

Per Nellgård ◽

...

Keyword(s):

Polyethylene Glycol ◽

Adverse Events ◽

Spinal Anesthesia ◽

Vital Signs ◽

Standard Of Care ◽

Holter Monitoring ◽

Serious Adverse Events ◽

Major Orthopedic Surgery ◽

American Society ◽

American Society Of Anesthesiologists

Background Hemospan (Sangart Inc., San Diego, CA), a polyethylene glycol-modified hemoglobin with unique oxygen transport properties, has successfully completed a phase I trial in healthy volunteers. Because adverse events are expected to increase with age, the authors conducted a phase II safety study of Hemospan in elderly patients undergoing elective hip arthroplasty during spinal anesthesia. Methods Ninety male and female patients, American Society of Anesthesiologists physical status I-III, aged 50-89 yr, in six Swedish academic hospitals were randomly assigned to receive either 250 or 500 ml Hemospan or Ringer's acetate (30 patients/group) before induction of spinal anesthesia. Safety assessment included vital signs and Holter monitoring from infusion to 24 h, evaluation of laboratory values, and fluid balance. The hypothesis to be tested was that the incidence of adverse events would be no more frequent in patients who received Hemospan compared with standard of care (Ringer's acetate). Results Three serious adverse events were noted, none of which was deemed related to study treatment. Liver enzymes, amylase, and lipase increased transiently in patients in all three groups. There were no significant differences in electrocardiogram or Holter parameters, but there was a suggestion of more bradycardic events in the treated groups. Hypotension was less frequent in the treated patients compared with controls. Conclusions In comparison with Ringer's acetate, Hemospan mildly elevates hepatic enzymes and lipase and is associated with less hypotension and more bradycardic events. The absence of a high frequency of serious adverse events suggests that further clinical trials should be undertaken.

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Efficacy and Safety of Pediatric Procedural Sedation Outside the Operating Room

Anesthesiology and Pain Medicine ◽

10.5812/aapm.106493 ◽

2020 ◽

Vol 10 (4) ◽

Author(s):

Thitima Sirimontakan ◽

Ninuma Artprom ◽

Nattachai Anantasit

Keyword(s):

Adverse Events ◽

Operating Room ◽

Demographic Data ◽

Procedural Sedation ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Physical Status Classification ◽

Sedation And Analgesia ◽

American Society ◽

American Society Of Anesthesiologists

Background: The volume of pediatric Procedural Sedation and Analgesia (PSA) outside the operating room has been increasing. This high clinical demand leads non-anesthesiologists, especially pediatric intensivists, pediatricians, and emergency physicians, to take a role in performing procedural sedation. Our department has established the PSA service by pediatric intensivists since 2015. Objectives: We aimed to assess the efficacy and safety of PSA outside the operating room conducted by pediatric intensivists and identify risk factors for severe adverse events. Methods: This was a retrospective descriptive study conducted from January 2015 to July 2019. Children aged less than 20 years who underwent procedural sedation were included. We collected demographic data, sedative and analgesic medications, American Society of Anesthesiologists (ASA) Physical Status Classification, indications for sedation, the success of procedural sedation, and any adverse events. Results: Altogether, 395 patients with 561 procedural sedation cases were included. The median age was 55 months (range: 15 to 119 months), and 58.5% (231/395) were male. The rate of successful procedures under PSA was 99.3%. Serious Adverse Events (SAE) occurred in 2.7%. Patients who received more than three sedative medications had higher SAE than patients who received fewer medications (adjusted for age, location of sedation, type of procedure, and ASA classification) (odds ratio: 8.043; 95% CI: 2.472 - 26.173, P = 0.001). Conclusions: Our data suggest that children who undergo procedural sedation outside the operating room conducted by pediatric intensivists are safe and effectively treated. Receiving more than three sedative medications is the independent risk factor associated with serious adverse events.

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Efficiency and Safety of the Selective Relaxant Binding Agent Adamgammadex Sodium for Reversing Rocuronium-Induced Deep Neuromuscular Block: A Single-Center, Open-Label, Dose-Finding, and Phase IIa Study

Frontiers in Medicine ◽

10.3389/fmed.2021.697395 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yanhua Zhao ◽

Sifan Chen ◽

Xiaorong Huai ◽

Zhangjie Yu ◽

Youmiao Qi ◽

...

Keyword(s):

Adverse Events ◽

Recovery Time ◽

Neuromuscular Block ◽

Dose Range ◽

Safety Data ◽

Dose Finding ◽

Dependent Manner ◽

Single Center ◽

Open Label ◽

Deep Neuromuscular Block

Background: Rapid reversal of neuromuscular block after surgery and anesthesia is often necessary. Here, we reported the primary efficacy and safety data from a phase IIa study on adamgammadex sodium, a newly developed modified γ-cyclodextrin derivative.Methods: This was a phase IIa, single-center, randomized, open-label, and dose-finding study that enrolled 35 patients under general anesthesia who received the neuromuscular blocking agent rocuronium for induction and maintenance of neuromuscular blockade. The subjects were randomized to one of the five adamgammadex dose groups (2, 4, 6, 8, and 10 mg kg−1) and to the 4 mg kg−1 sugammadex group. Pharmacological efficacy was the recovery time from the start of adamgammadex or sugammadex administration to train-of-four (TOF) ratio ≥0.9, 0.8, and 0.7 among the different dose groups. Adverse events were recorded throughout the study.Results: The efficacy in reversing deep neuromuscular block was the same between 4 mg kg−1 sugammadex and adamgammadex. However, in the lowest dose groups of 2 and 4 mg kg−1 adamgammadex, adequate reversal could not be achieved in all subjects. The recovery time of TOF ratio to 0.9, 0.8, and 0.7 was shorter in the adamgammadex 10 mg kg−1 group than in the sugammadex 4 mg kg−1 group. The average values of the TOF ratio after 3 min of administration of adamgammadex 8 and 10 mg kg−1 and sugammadex 4 mg kg−1 were >90%. There were no serious adverse events after the use of adamgammadex, and no subjects had to be withdrawn from the trial.Conclusions: Adamgammadex enabled quick, predictable, and tolerable reversion of rocuronium-induced deep neuromuscular block in a dose-dependent manner. Adamgammadex doses of 6–10 mg kg−1 might be the recommended dose range for further exploration of efficacy. Clinical Trial Registration: This study was registered at chictr.org.cn, identifier: ChiCTR2000038391.

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