Sugammadex

Aka: Sugammadex, Bridion

1. Indications
   1. Rapid reversal of Rocuronium and Vecuronium (Non-depolarizing Neuromuscular Blocking Agents)
   2. FDA approved for reversal in adult surgery cases, to speed recovery after case completion
   3. Follow neurologic status in neurologic catastrophe (e.g. Intracranial Hemorrhage) or Status Epilepticus
2. Precautions: Emergency Paralytic Reversal
   1. Emergency paralytic reversal is off-label use and may not be ideal
      1. A patient who requires emergent Endotracheal Intubation still needs an airway
      2. Reversal agents render further Non-depolarizing Neuromuscular Blocking Agent use ineffective
   2. Can't Intubate but CAN ventilate scenarios may be treated with temporarily with BVM or LMA
   3. Can't Intubate, Can't Ventilate scenarios require emergency Cricothyrotomy
      1. Paralysis reversal may worsen this situation and delay definitive management
   4. References
      1. Strayer in Herbert (2019) EM:RAP 19(11):4-6
3. Background
   1. Approved in Europe in 2008
   2. FDA approved in U.S. in 2016 (initially rejected due to Anaphylaxis risk)
4. Mechanism
   1. Sugammadex is a modified gamma cyclodextrin that tightly binds Rocuronium and Vecuronium
   2. Reduces available Rocuronium and Vecuronium to bind nicotinic acetylcholine receptors at neuromuscular junction
5. Pharmacokinetics
   1. Reverses paralysis within 3-5 minutes
   2. Not metabolized
      1. Up to 95% if excreted unchanged in the urine
   3. Half-Life
      1. Normal Renal Function: 2 hours
      2. Mild renal Impairment: 4 hours
      3. Moderate renal Impairment: 6 hours
      4. Severe renal Impairment: 19 hours
   4. Continues to block Neuromuscular Blockade until cleared (based on weight and Renal Function)
      1. Requires delay if another neuromuscular blocker needs to be given
      2. Consider nonsteroidal neuromuscular blocker if another paralytic is needed
6. Dosing
   1. Reversal of moderate Neuromuscular Blockade
      1. Dose: 2 mg/kg total body weight
   2. Reversal of deep Neuromuscular Blockade (typical dose)
      1. Dose: 4 mg/kg total body weight
   3. Rapid reversal dose (difficult intubation and ventilation, onset within 3 min)
      1. Dose: 16 mg/kg total body weight
   4. Minimum wait times to re-dose neuromuscular blocking agent (NMBA)
      1. Indications to wait >5 minutes
         1. Standard dosing with normal Renal Function
         2. However if NMBA given within 30 minutes of Sugammadex expect modified pharmacokinetics
            1. Onset delayed up to 4 minutes from time of administration
            2. Duration of action may be decreased to as short as 15 minutes
      2. Indications to wait 24 hours
         1. High dose Sugammadex given (16 mg/kg)
         2. Renal Impairment
7. Adverse Effects
   1. Recurrent Neuromuscular Blockade
      1. Drug Interactions may displace Sugammadex from binding NMBA, resulting in recurrent Neuromuscular Blockade
   2. Severe Bradycardia (1 to 5%)
      1. Onset within minutes of administration
      2. May require Atropine
      3. Cardiac Arrest has occurred in some cases
   3. Prolonged QT Interval (6%)
   4. Hypotension (4 o 13%)
   5. Anaphylaxis or anaphylactoid reactions (0.3% to 1%)
      1. Dose dependent risk (higher doses are higher risk for Anaphylaxis)
   6. Other adverse effects
      1. Nausea or Vomiting
      2. Pain
      3. Headache
8. References
   1. Braude and Hayes in Herbert (2016) EM:Rap 16(11): 7
   2. Whiting and LoVecchio (2018) Crit Dec Emerg Med 32(11): 28
   3. Mishler and LoVecchio (2017) Crit Dec Emerg Med 31(5): 24