Ultra-Rapid Reversal of Rocuronium-Induced Paralysis with Sugammadex in the Emergency Department
4
Citation
10
Reference
10
Related Paper
Citation Trend
Keywords:
Sugammadex
Rapid sequence induction
Neuromuscular Blocking Agents
Background Sugammadex selectively binds steroidal neuromuscular blocking drugs, leading to reversal of neuromuscular blockade. The authors developed a pharmacokinetic-pharmacodynamic model for reversal of neuromuscular blockade by sugammadex, assuming that reversal results from a decrease of free drug in plasma and/or neuromuscular junction. The model was applied for predicting the interaction between sugammadex and rocuronium or vecuronium. Methods Noninstantaneous equilibrium of rocuronium-sugammadex complex formation was assumed in the pharmacokinetic-pharmacodynamic interaction model. The pharmacokinetic parameters for the complex and sugammadex alone were assumed to be identical. After development of a pharmacokinetic-pharmacodynamic model for rocuronium alone, the interaction model was optimized using rocuronium and sugammadex concentration data after administration of 0.1-8 mg/kg sugammadex 3 min after administration of 0.6 mg/kg rocuronium. Subsequently, the predicted reversal of neuromuscular blockade by sugammadex was compared with data after administration of up to 8 mg/kg sugammadex at reappearance of second twitch of the train-of-four; or 3, 5, or 15 min after administration of 0.6 mg/kg rocuronium. Finally, the model was applied to predict reversal of vecuronium-induced neuromuscular blockade. Results Using the in vitro dissociation constants for the binding of rocuronium and vecuronium to sugammadex, the pharmacokinetic-pharmacodynamic interaction model adequately predicted the increase in total rocuronium and vecuronium plasma concentrations and the time-course of reversal of neuromuscular blockade. Conclusions Model-based evaluation supports the hypothesis that reversal of rocuronium- and vecuronium-induced neuromuscular blockade by sugammadex results from a decrease in the free rocuronium and vecuronium concentration in plasma and neuromuscular junction. The model is useful for prediction of reversal of rocuronium and vecuronium-induced neuromuscular blockade with sugammadex.
Sugammadex
Pharmacodynamics
Cite
Citations (46)
Editor, Sugammadex provides fast dose-dependent reversal of neuromuscular blockade (NMB) by rocuronium. However, delayed recovery has been reported.1 We would like to report a case of failure of sugammadex to reverse rocuronium NMB. A 60-year-old man, weight 115 kg, height 175 cm, American Society of Anesthesiologists' (ASA) physical status 2 (arterial hypertension) was anaesthetised for laparoscopic resection of the sigmoid colon. He received midazolam and target-controlled infusions of propofol and remifentanil. NMB monitoring was performed using train-of-four (TOF) nerve stimulation with acceleromyography (TOF-Watch SX, Bluestar Enterprises, Omaha, Nebraska, USA) at the adductor pollicis muscle following internationally accepted rules2 and calibrated before the administration of succinylcholine 100 mg (risk of difficult intubation or ventilation). The trachea was intubated within 2 min (single twitch height = 0%). Seven minutes after administration of suxamethonium, recovery was observed (movements and acceleromyographic evidence) and a 2× ED95 bolus dose of rocuronium (70 mg) was administered. Central body temperature was measured and maintained using standard techniques of heat conservation. A continuous infusion of rocuronium 1 to 4 μg kg−1 min−1 (total 83 mg) was used to maintain a posttetanic count of zero to one responses. The patient also received cefotaxime, metronidazole, dexamethasone, ondansetron, pantoprazole and morphine. At the end of the 6 h operation (and 27 min after the rocuronium infusion was stopped) with one TOF response (T1 height amplitude 4%), he was given intravenous sugammadex 4 mg kg−1 (460 mg), but 5.5 min later, NMB was unchanged. Further doses of sugammadex were administered: 4 mg kg−1 at 5.5 min; and 200 mg at 11.5 min, both without clinical and acceleromyographic effect, with a total dose of 1120 mg (9.74 mg kg−1). To exclude malfunction of the TOF-Watch, a different peripheral nerve stimulator was used at the facial nerve, with the same visual result as in the adductor pollicis: one weak response to TOF stimulation. Neostigmine 1 mg was then injected 26.5 min after the first dose of sugammadex, and 1.5 mg 3 min later. The patient started breathing spontaneously, but was still curarised (four responses to TOF with T1 of 8 to 9% in the adductor pollicis muscle, four weak responses to TOF stimulation at the facial nerve, low inspiratory volumes, carbon dioxide retention, sweating and so on), so he was transferred intubated to the postanaesthesia care unit and extubated there without incident 3 h later. There are several possible explanations for our observation, relating to the drug, the monitoring or the patient. There was evidence of recovery from succinylcholine, so an abnormal effect of the drug or impaired plasma cholinesterase activity was rejected. An administration error was excluded after checking medication vials used and faulty medications were also dismissed because drugs are kept in accordance with the manufacturer's recommendations and subsequent doses of the same batch of sugammadex and rocuronium were used without problems. An NMB monitor malfunction was rejected because the TOF-Watch SX performed normally before and after this case, the patient remained in the same position with his hand properly secured during surgery and its data were consistent with the second NMB monitor and the clinical signs. Hypothermia was excluded and there were no ionic or pH alterations or diseases that could explain these findings; renal function was normal, and the patient was neither a smoker nor drinker and had no hepatic or neuromuscular diseases. Drug interactions were also considered. Sugammadex has been specifically designed to form high-affinity complexes with rocuronium, but might also form complexes with other molecules. Interactions could be due to capture or displacement reactions.3 In a capturing reaction, when the affinity of sugammadex for a certain molecule is sufficiently high, sugammadex may encapsulate it and reduce the effect of the remaining drug. In a displacement reaction, after successful NMB reversal, administration of another molecule with high-affinity for sugammadex may displace a fraction of the encapsulated rocuronium from its complex with sugammadex, potentially resulting in recurrence of NMB. The drugs identified with potential interactions with sugammadex include toremifene, flucloxacillin, fusidic acid and the oral contraceptive pill. There is no previous evidence of an interaction between sugammadex and the anaesthetic drugs used in this case, nor with the patient's regular medication (valsartan and hydrochlorothiazide). Other possibilities such as an endogenous molecule in the patient, or even immunological resistance to cyclodextrins, might be considered; of note, cyclodextrins are normal molecules in our daily diet (4 g per day). Overall, this hypothesis seems unlikely unless a very potent displacement reaction occurs, because with the high doses of sugammadex used, at least a minimal recovery response should have been seen. The reversal of rocuronium by sugammadex is very selective and both molecules bind in a 1 : 1 molar ratio, so one molecule of sugammadex (molecular weight of 2.178 kDa) antagonises one molecule of rocuronium (610 kDa); thus, theoretically, 3.57 mg of sugammadex is required to bind 1 mg of rocuronium.4 This patient received 1160 mg of sugammadex and 153 mg of rocuronium (2 : 1 molar ratio), which should have been a sufficient dose to cause a substantial reversal despite drug interactions unless a displacement reaction was potent enough to cause almost immediate recurarisation. Finally, and this is the explanation that the authors believe to be probable, this patient may be what is described in statistical terms as 'an extreme outlier'. Usually, when we use a drug in the clinical scenario, the drug has been studied previously in a large number of patients, and the doses recommended are the most common for almost everybody.5 A small number of patients, however, have either a left-shift of the dose–response curve (more sensitivity to the drug) or a right-shift (relative resistance to the drug). We suggest that this case report represents an extreme outlier with a marked rightward shift of the dose–response curve. Sugammadex has been described as the ideal reversal drug.1 Nevertheless, delayed recovery has been described previously;6,7 in these cases, the time to recovery of TOF ratio to 0.9 after treatment with sugammadex 4 mg kg−1 took 24.6 and 22.3 min respectively, compared with a mean of 173 s in other patients. The present case report shows not just delay but failure to reverse rocuronium 45 min after the first dose of sugammadex was administered. These data suggest that excessive NMB depth should not be considered a well tolerated practice in all circumstances, because there are some patients (though very rare) in whom fast reversal with sugammadex may not be achievable. Acknowledgements relating to this article Assistance with the letter: we would like to thank the patient for his kindness in giving written informed consent for publication. Conflict of interests: none. Financial support and sponsorship: none.
Sugammadex
Bolus (digestion)
Rocuronium Bromide
Neuromuscular monitoring
Midazolam
Cite
Citations (22)
Survey of Anesthesiology: June 2008 - Volume 52 - Issue 3 - p 138-139 doi: 10.1097/SA.0b013e318179f0ef
Sugammadex
Cite
Citations (0)
(Abstracted from J Clin Anesth, 35:497–501, 2016) Sugammadex is a selective muscle relaxant binding agent with a γ-cyclodextrin structure, which reverses rocuronium- and vecuronium-induced neuromuscular blockade by chemical encapsulation. The objective of this retrospective, observational study was to evaluate the efficacy and safety of sugammadex for the reversal of profound neuromuscular blockade by rocuronium in infant patients.
Sugammadex
Muscle relaxant
Rocuronium Bromide
Cite
Citations (0)
Duvaldestin, P.; Kuizenga, K.; Kjaer, C C.; Saldien, V.; Debaene, B. Author Information
Sugammadex
Vecuronium bromide
Neuromuscular monitoring
Cite
Citations (10)
In many procedures requiring intubation neuromuscular blocking agents are administered during anesthesia to facilitate the intubation of the trachea and to optimize the surgical field. For short procedures (e.g., less than 30 minutes), a short acting neuromuscular blocking agent, such as succinylcholine, is required for rapid sequence induction and intubation. Succinylcholine, a depolarizing neuromuscular blocking agent, produces a reliable neuromuscular block (NMB), has the fastest onset and the shortest duration of all neuromuscular blocking agents, and the recovery of the NMB typically occurs by spontaneous recovery.Alternatives to succinylcholine may include using a longer acting neuromuscular blocking agent in conjunction with a reversal agent to produce a short-term NMB. Rocuronium is a non-depolarizing neuromuscular blocking agent with fast onset, which can be used at higher doses for rapid sequence induction and intubation. Sugammadex is a selective relaxant binding agent indicated for the reversal of moderate to deep NMB, with a high affinity for rocuronium.,A manufacturer shortage of succinylcholine occurred in Canada in May 2019, and at the time this report was written, the drug shortage was anticipated to last until mid-August 2019. In these circumstances, the use of rocuronium with sugammadex may be an alternative to succinylcholine when there is a need for short acting NMB. Neuromuscular blocking agents and reversal agents are associated with various adverse effects, including residual NMB, myalgias, muscle fasciculations, headache, nausea, and vomiting,, and it is unclear how the clinical benefits and harms of using rocuronium with sugammadex compare with using succinylcholine alone. In addition, the cost of sugammadex is significantly higher than other common reversal agents (e.g., neostigmine), and it is unknown if sugammadex is cost effective for routine clinical use.The purpose of this report is to synthesize and critically appraise the available evidence on the clinical effectiveness of rocuronium with sugammadex compared to succinylcholine in patients undergoing surgery who require rapid sequence induction. Additionally, the cost-effectiveness of sugammadex in patients undergoing surgery will be reviewed. This information may be used to inform decision making relating to health policy of the use of sugammadex.
Sugammadex
Neuromuscular Blocking Agents
Rapid sequence induction
Neuromuscular transmission
Neuromuscular monitoring
Muscle relaxation
Cite
Citations (0)
Background: Sugammadex is a new reversal agent for nondepolarizing neuromuscular blockade. We conducted the randomized clinical study to compare the recovery between sugammadex alone and combined use of sugammadex and neostigmine.
Methods: Forty adult patients were randomly allocated to Group S (n=20) or Group SN (n=20). General anesthesia was induced and maintained with propofol and remifentanil. The patients were intubated without neuromuscular blockers. After the stabilization of TOF Watch SX® acceleromyography as control, rocuronium 0.6 mg/kg was administered to patients in both groups. The patients in Group S received sugammadex 1.0 mg/kg and those in Group SN received sugammadex 0.5 mg/kg, neostigmine 0.04 mg/kg and atropine 0.02 mg/kg five minutes after rocuronium administration. The cost of reversal and recovery time were measured in both groups.
Results: We analyzed the data of 36 patients (n=18 in each group). The T1/control ratios were significantly higher in Group SN than in group S at 5, 10 and 15minutes after administration of reversal agents. The TOF ratios were significantly higher in Group SN than in group S at 10 and 15minutes after administration of reversal agents. The 90% recovery time of TOF ratio in Group SN was significantly shorter than that in Group S. The cost of reversal was significantly smaller in Group SN than in Group S.
Conclusions: By partially substituting sugammadex with neostigmine, we can attain faster recovery from rocuronium-induced profound neuromuscular blockade.
Sugammadex
Rocuronium Bromide
Cite
Citations (6)
In Brief BACKGROUND: Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular blockade in patients induced and maintained under propofol anesthesia. However, sevoflurane anesthesia, unlike propofol, can prolong the effect of neuromuscular blocking drugs (NMBDs) such as rocuronium and vecuronium. METHODS: We designed this randomized, open-label, dose-response trial to explore the dose-response relationship of sugammadex for the reversal of deep neuromuscular blockade induced by rocuronium or vecuronium under propofol-induced and sevoflurane-maintained anesthesia. As a secondary objective, the safety variables of sugammadex were evaluated. After anesthesia induction with propofol, 102 patients aged ≥20 and <65 yr were randomized to receive a single bolus dose of rocuronium 0.9 mg/kg (n = 50) or vecuronium 0.1 mg/kg (n = 52), followed by maintenance doses (rocuronium 0.1-0.2 mg/kg or vecuronium 0.02-0.03 mg/kg) as needed. Neuromuscular blockade was monitored using acceleromyography. After the last dose of NMBD, at 1-2 posttetanic counts, a single bolus dose of sugammadex 0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg was administered. The primary efficacy variable was time from start of sugammadex administration to recovery of the T4/T1 ratio to 0.9. RESULTS: The per-protocol population consisted of 48 patients in the rocuronium group and 47 in the vecuronium group. A dose-response effect was demonstrated for decreased mean time to recovery of the T4/T1 ratio to 0.9 with increasing sugammadex dose in both NMBD groups (per-protocol population): rocuronium group, 79.8 (sd 33.0) min (sugammadex 0.5 mg/kg) to 1.7 (0.7) min (4.0 mg/kg) and 1.1 (0.3) min (8.0 mg/kg subgroup); vecuronium group, 68.4 (31.9) min (0.5 mg/kg) to 3.3 (3.5) min (4.0 mg/kg), and 1.7 (0.8) min (8.0 mg/kg subgroup). Neuromuscular monitoring showed recurrent neuromuscular blockade in 5 patients, all in the rocuronium group (2 given sugammadex 0.5 mg/kg and 3 given 1.0 mg/kg), but there were no clinical events attributable to recurrent or residual neuromuscular blockade. CONCLUSION: Sugammadex at doses of ≥4 mg/kg provides rapid reversal of deep rocuronium- and vecuronium-induced neuromuscular blockade under sevoflurane maintenance anesthesia. Published ahead of print November 21, 2009
Sugammadex
Muscle relaxant
Bolus (digestion)
Rocuronium Bromide
Cite
Citations (132)
University Department of Anaesthesia, Royal Liverpool University Hospital, Liverpool, United Kingdom
Sugammadex
Neuromuscular monitoring
Rocuronium Bromide
Cite
Citations (3)
Sugammadex reversiert die Wirkung von Rocuronium durch Enkapsulierung ohne muskarinerge Nebenwirkungen. Bisherige publizierte Studien zeigen eine effektive dosisabhängige Reversierung der neuromuskulären Blockade nach Verwendung von Rocuronium oder Vecuronium. Wir berichten in unserem Fallbericht von einem Patienten, der am Ende der OP nach RSI mit Rocuronium eine tiefe neuromuskuläre Blockade zeigte, die innerhalb weniger Minuten nebenwirkungsfrei reversiert werden konnte.
Sugammadex
Rapid sequence induction
Continuous Infusion
Muscle relaxation
Neuromuscular monitoring
Cite
Citations (0)