Created August 9, 2015, last updated 29 days ago.
Collection: 38, Score: 2982, Trend score: 0, Read count: 2980, Articles count: 19, Created: 2015-08-09 06:20:49 UTC. Updated: 2020-05-18 07:20:12 UTC.
Possibly... but with some important caveats.
“Sugammadex is likely the most exciting drug in clinical neuromuscular pharmacology since the introduction of atracurium and vecuronium in the middle 1980s.” – RD Miller (2007).
Sugammadex (Bridion®) is a remarkable drug – and the anaesthesia community has moved very quickly to embrace the potential of this first ‘selective relaxant binding agent’ (SRBA), despite it’s considerable cost.
Sugammadex offers a new and improved way of reversing aminosteroid muscle relaxation, in particular from rocuronium. The speed at which it reverses even profound neuromuscular blockade is incredible and potentially life saving. Sugammadex’s onset is 10 times faster than neostigmine and three times faster than edrophonium.
Though beyond the parlour-trick of speedy action, or the possibility of rescuing a cannot-intubate-cannot-ventilate crisis – the biggest benefit of sugammadex for our patients may be in the dramatic reduction of post-operative residual paralysis. A common problem with serious consequences that the anaesthetic community has ignored for far too long.
A collection of evidence looking specifically at the issue of our poor stewardship of neuromuscular blocking agents can be found here: Neuromuscular myths: the lies we tell ourselves
Important caveats to temper our sugammadex enthuasiasm...
- Sugammadex is still cost-prohibitive for many health systems.
- Although neuromuscular reversal is demonstrably better than for neostigmine, sugammadex use does not obviate the need for neuromuscular monitoring (Kotake 2013: Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block).
- Sugammadex is an important option to consider in a CICO crisis, but it is not a ‘Get Out of Gaol Free’ card (Kyle 2012: A persistent 'can't intubate, can't oxygenate' crisis despite rocuronium reversal with sugammadex).
- Sugammadex is now the leading cause of perioperative anaphylaxis in Japan, and we have likely underestimated the risk of sugammadex hypersensitivity. (see: Sugammadex anaphylaxis: all that glitters?).
Miller enthusiastically states:
“Sugammadex is likely the most exciting drug in clinical neuromuscular pharmacology since the introduction of atracurium and vecuronium in the middle 1980s.”
...and hints at where benefits may begin:
“Will sugammadex’s increased effectiveness, in comparison to neostigmine, lessen the need for or use of monitoring neuromuscular function?”
Randomized Controlled Trial Comparative Study
Time to achieve full reversal (TOFR > 0.9) was significantly faster with sugammadex (107s ± 61) than neostigmine (1044 ±590s) or edrophonium (331s ± 27).
All sugammadex-reversed patients were completely reversed within 5 minutes, compared with no patients receiving neostigmine.
Reversal with sugammadex lead to less increase in heart-rate than when neostigmine-glycopyrrolate or edrophonium-atropine and almost total avoidance of the dry-mouth associated with the later (5% vs 85-95%)summary
Review Meta Analysis
Abrishami et al.'s Cochrane review of 18 RCTs totalling 1,300 patients confirmed the superiority of sugammadex compared with neostigmine at all studied levels of blockade. They identified sugammadex dosing of:
- 2 mg/kg - for reversal of rocuronium neuromuscular blockade at TOF-T2 reappearance.
- 4 mg/kg - for reversal at post-tetanic count of 1 to 2.
- 16 mg/kg - for reversal 3 to 5 minutes after a rocuronium intubating dose.
Importantly there was similar frequency of adverse events compared to neostigmine (< 1%), although overall small sample sizes mean no conclusion can be made regarding rare serious adverse events.summary
Neville Gibbs and Peter Kam outline three evidence-based indications for use of sugammadex in 2012, even with its high cost:
Early reversal of rocuronium when suxamethonium is contraindicated. For example in ECT for patients with a pseudocholinesterase deficiency or neuromuscular denervation conditions.
Reversal of rocuronium when even very mild residual neuromuscular block carries significant patient risk. For example, patients with neuromuscular disorders such as myotonic dystrophy or myasthenia gravis; and patients with severe pulmonary disease with limited reserve.
Unplanned early reversal of rocuronium during a failed intubation where rapid reversal may allow awakening of the patient.
Rescue from residual paralysis despite having given neostigmine.
Review Meta Analysis Comparative Study
An early review and economic study of the cost effectiveness of sugammadex, concluding that it may be cost effective to routinely reverse with sugammadex if there are significant time savings in the operating theatre, but not if the time savings occur instead in the PACU.
The study assumed NHS costs of operating room time of £266/h (US$412/h) and PACU time of £20/h (US$31/h).summary
Ledowski et al. investigated the effect of unrestricted access to sugammadex in an Australian teaching hospital with a retrospective observational audit.
Use of both sugammadex and amino steroid relaxants increased dramatically, with average reversal costs per case increasing by AUS$85.
Although there was no change in anaesthesia, surgical or PACU time, there was a statistically significant decrease in median time from surgery to hospital discharge (0.2 days shorter) after introduction of sugammadex. Do to the nature of the study, it is nevertheless impossible to infer a causal link.summary
This retrospective audit identified an association between the introduction of unrestricted access to sugammadex and a fall in 'anaesthetic theatre time'. Mean hospital stay was also observed to be 0.8 days shorter after introduction of sugammadex, but was not statistically significant after adjusting for confounders.summary
Randomized Controlled Trial
Randomized Controlled Trial
An interesting CICO case study highlighting that while sugammadex will rapidly and completely reverse paralysis, this is only one consideration when managing an airway crisis. The use of any reversal agent in an airway crisis should be considered within the context of the case and a clear understanding of the objective of our actions.
Neuromuscular reversal will only improve a CICO scenario if spontaneous ventilation will improve patient oxygenation, otherwise return of muscle function may actually make other CICO interventions more difficult.summary
A reminder that hypersensitivity reactions are possible with almost any drug or chemical. At the time of this publication, the risk of anaphylaxis to sugammadex appeared to be lower than that for muscle relaxants – however newer studies from Merck (Kam 2018 and Min 2018) worryingly suggest that sugammadex sensitivity may be a lot more common than we thought.
The FDA’s caution now no longer seems quite so unwarranted...summary
Randomized Controlled Trial Multicenter Study
Reversal of the residual effect of rocuronium or cisatracurium by neostigmine may be slow and associated with side-effects. This randomized, safety-assessor-blinded study compared the efficacy of sugammadex, a selective relaxant binding agent for reversal of rocuronium-induced neuromuscular block, with that of neostigmine for reversal of cisatracurium-induced neuromuscular block. The safety of sugammadex and neostigmine was also evaluated. ⋯ Sugammadex 2.0 mg kg(-1) administered at reappearance of T(2) was significantly faster in reversing rocuronium-induced blockade than neostigmine was in reversing cisatracurium-induced block.
Randomized Controlled Trial Multicenter Study Comparative Study
Adequate recovery from neuromuscular block (NMB) is imperative for the patient to have full control of pharyngeal and respiratory muscles. The train-of-4 (TOF) ratio should return to at least 0.90 to exclude potentially clinically significant postoperative residual block. Fade cannot be detected reliably with a peripheral nerve stimulator (PNS) at a TOF ratio >0.4. The time gap between loss of visual fade by using a PNS until objective TOF ratio has returned to >0.90 can be considered "the potentially unsafe period of recovery." According to our hypothesis the duration of this period would be significantly shorter with sugammadex than with neostigmine. ⋯ There is a significant time gap between visual loss of fade and return of TOF ratio >0.90 after reversal of a rocuronium block by neostigmine. Sugammadex in comparison with neostigmine allows a safer reversal of a moderate NMB when relying on visual evaluation of the TOF response.
Sugammadex is a selective binding agent for aminosteroid neuromuscular blockers whose use is increasing in anaesthetic practice. We present three cases of severe anaphylaxis coincident with sugammadex administration. ⋯ As all patients were administered sugammadex to reverse neuromuscular blockade with rocuronium, we considered that sugammadex-rocuronium complexes were a potential unique allergen. In the two patients who were additionally tested with a rocuronium-sugammadex (3.6:1 molecular ratio) mixture, the wheal-and-flare response was significantly attenuated.
The authors suggest a possible revision of anaesthesia consent, such as:
"You may receive medications during your anesthetic that could interfere with the effectiveness of oral contraceptives. If you are using oral contraceptives, consider alternative methods of birth control for 7 days following your anesthetic." This disclosure would cover potential interactions with sugammadex, antibiotics, and other medications.
Note the authors: “So long as neostigmine and glycopyrrolate are available and not prohibitively expensive, we should make a point in our practice to not use sugammadex for rocuronium reversal in women of childbearing age in situations where neostigmine and glycopyrrolate will have equal effectiveness.”summary
Five percent of adult patients undergoing noncardiac inpatient surgery experience a major pulmonary complication. The authors hypothesized that the choice of neuromuscular blockade reversal (neostigmine vs. sugammadex) may be associated with a lower incidence of major pulmonary complications. ⋯ Among a generalizable cohort of adult patients undergoing inpatient surgery at U.S. hospitals, the use of sugammadex was associated with a clinically and statistically significant lower incidence of major pulmonary complications.