Vecuronium


Article Author:
Mark Ramzy


Article Editor:
Russell McAllister


Editors In Chief:
Chaddie Doerr


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Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
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John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes
Kavin Sugumar


Updated:
4/5/2019 10:42:32 PM

Indications

Vecuronium Bromide is an FDA approved peripherally acting, monoquarternary, steroidal, non-depolarizing neuromuscular blocker with an intermediate duration of action used during general anesthesia to facilitate endotracheal intubation, to aid in surgical relaxation, and, less commonly, in the intensive care setting to achieve paralysis to facilitate mechanical ventilation in adequately sedated patients. This neuromuscular blocking agent is often used to facilitate endotracheal intubation and surgical relaxation in patients under general anesthesia.  It is structurally similar to pancuronium, differing only by the lack of a quaternizing methyl group in the 2-piperidino substitution.  This results in a slight decrease in potency and an elimination of the vagolytic properties when compared to pancuronium.  Vecuronium also has higher lipid solubility which results in a higher amount of biliary elimination.  [1]

Vecuronium is chiefly eliminated by the liver due to its higher lipid solubility.  Poor liver function can cause prolonged effects.  Vecuronium has three possible metabolites, The three hydroxy metabolite has 80% the neuromuscular blocking potency of vecuronium.  Therefore, prolonged use of vecuronium can result in accumulation of this metabolite and significantly prolonged neuromuscular blocking effects.  Renal excretion accounts for only about 30% of the elimination of vecuronium.  

Vecuronium has rarely been used off-label to control refractory shivering in sedated patients during administration of post-cardiac arrest therapeutic hypothermia. However, in this setting, the duration of action is prolonged, and it may mask seizure activity.[2][3]

Mechanism of Action

Vecuronium is a nondepolarizing agent that achieves its skeletal muscle paralysis by competing with acetylcholine for cholinergic receptor sites and binding with the nicotinic cholinergic receptor at the postjunctional membrane. The neuromuscular blocking properties of vecuronium are antagonized by anticholinesterases.[4]  In addition, the effects of vecuronium can be reversed by sugammadex, a modified cyclodextrin which encapsulates the compound, rendering the drug ineffective.

When a patient is under balanced anesthesia, the time to recover to 25% of control is approximately 25 to 40 minutes, and recovery is usually 95% complete at about 45 to 65 minutes after the intubating dose. The presence of halogenated volatile anesthetics such as sevoflurane or desflurane slightly enhances the neuromuscular blocking action of vecuronium. If vecuronium is administered in conjunction with an inhalation induction of anesthesia with a volatile agent, the intubating dose of vecuronium is typically decreased by 15% due to the mild muscle relaxation effects of the halogenated volatile anesthetic.

Administration

Vecuronium is prepared as a lyophilized powder because it has poor stability in solution, and therefore would have a very short shelf life in this form.  This requires reconstitution of the drug prior to administration.  

The dose used for endotracheal intubation in the controlled setting prior to surgery:

0.08 mg/kg to 0.1 mg/kg intravenous (IV) over 60 seconds or 0.04 mg/kg to 0.06 mg/kg IV if succinylcholine was used, to allow its effects to subside before administering vecuronium.

The dose used for rapid sequence intubation:

  • 0.1 mg/kg to 0.2 mg/kg IV, with the onset of intubation conditions occurring in less than 2 to 3 minutes

Maintenance for continued surgical relaxation:

  • 0.01 mg/kg to 0.015 mg/kg IV to be given 20 to 45 minutes after the initial dose and every 12 to 15 minutes as needed

Maintenance for continuous Infusion (most commonly used for ICU paralysis to facilitate mechanical ventilation):

  • Initial bolus dose of 0.08 mg/kg to 0.1 mg/kg IV starting 20 minutes post bolus recovery, followed by 0.05 mg/kg/hour to 0.07 mg/kg/hour IV.

Adverse Effects

The following adverse reactions have occurred in less than 1% of cases:

  • Bronchospasm
  • Hypotension
  • Edema
  • Sinus Tachycardia
  • Erythema
  • Urticaria
  • Flushing
  • Pruritus
  • Skin Rash

Hypersensitivity associated with histamine release leading to allergic reactions may occur, and in rare instances, life-threatening anaphylaxis may occur.  In general, when compared to other nondepolarizing neuromuscular-blocking agents such as pancuronium, rocuronium or atracurium, the safety profile of vecuronium is favorable.  [5]

Contraindications

Of all the neuromuscular blocking agents, vecuronium is associated with the least amount of histamine release; however severe, life-threatening anaphylactic reactions can still occur and have been reported. Due to the excessive salivation that can occur with this histamine release, caution should be used when administering vecuronium to patients with bronchospasm and asthma. [1]

Electrolyte abnormalities such as severe hypocalcemia, hypokalemia, or hypomagnesemia may potentiate the effects of vecuronium. Other relative contraindications to the use of vecuronium include myopathy, obesity, and neuromuscular diseases, such as Eaton-Lambert syndrome and myasthenia gravis, as these conditions may prolong the drug’s effect.

Vecuronium should be used with caution in patients with underlying cardiac disease that may be associated with slower circulation time. Edema, poor circulation, and changes in fluid volume can delay the onset of muscle paralysis.

Due to its clearance via the liver, vecuronium should be used with caution in patients with liver failure or cirrhosis. Prolonged recovery from muscle paralysis may occur in patients with any kind of underlying liver disease. Caution should also be used when administering vecuronium to renal failure patients, as hepatic elimination is decreased in patients with uremia, and this may cause accumulation of the drug’s active 3-hydroxy metabolite.

Caution is advised when administering vecuronium to patients with burns greater than or equal to 20% of their total body surface area. Resistance to the muscle paralysis caused by vecuronium may occur several days after the injury and persist for several months after wound healing. 

Monitoring

Due to the respiratory insufficiency caused by paralyzing respiratory muscles, vecuronium only should be administered by experienced healthcare providers equipped with the necessary skills for advanced airway management. Assisted or controlled ventilation through the use of a bag-valve-mask connected to a supplemental oxygen or a mechanical ventilator should be readily accessible. Closely monitor the patient's blood pressure, heart rate, and peripheral nerve stimulation prior to administering vecuronium. Furthermore, the clinician should also have reversal agents immediately available.

Toxicity

Anticholinesterases antagonize neuromuscular blockade action; therefore, the use of acetylcholinesterase inhibitors such as neostigmine can be used to reverse rocuronium and vecuronium's effect on muscle paralysis. Anticholinergic agents such as glycopyrrolate must be administered to offset the bradycardic effects seen with anticholinesterase drugs. Furthermore, in bradycardic patients, the anticholinergic drug may be given first.

Sugammadex is a new selective relaxant-binding agent that forms a complex with vecuronium and rocuronium thus reducing the amount of drug available to bind to nicotinic cholinergic receptors. Decreasing the amount of drug available at the neuromuscular junction successfully reverses muscle paralysis. Although vecuronium has more than five times the potency of rocuronium, studies have shown that the use of sugammadex results in significantly faster recovery from vecuronium-induced muscle paralysis when compared to neostigmine.  Due to the higher cost of suggamadex compared to neostigmine/glycopyrrolate, the cost benefit analysis of drug selection must be considered.  Sugammadex reversal also has implications in females of child bearing age, as it can also encapsulate oral contraceptive agents, rendering the ineffective.  Patients must be advised to use alternate forms of birth control over the ensuing weeks.   [6][7][8][7]

Vecuronium is a pregnancy category C drug. It is not known if it is excreted in breast milk and the effect on a nursing infant not known. It has been used safely for surgical relaxation for caseraen sections under general anesthesia.

Enhancing Healthcare Team Outcomes

Vecuronium is most often used by the anesthesiologist, anesthesia nurse, emergency department physician, and the intensivist. It is vital that before administering this agent one have resuscitative equipment including a mechanical ventilator in the room. The patient must have an intravenous line and should be monitored by a dedicated nurse during the process of intubation. Furthermore, the clinician should also have reversal agents immediately available.


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Vecuronium - Questions

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A patient on a mechanical ventilator has respiratory efforts that are not synchronous with the ventilator, resulting in elevated peak airway pressures and ineffective ventilation. Ventilator settings have been adjusted and the patient sedated with midazolam and propofol, but the issue has not resolved. What medication should be considered at this time?



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The duration of action for vecuronium is increased in patients with which of the following diseases?



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Which of the following medication dosages would not be altered for a patient in advanced age?



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A previously healthy 27-year-old man presents to the operating room for laparoscopic cholecystectomy. During induction of general anesthesia, a standard intubating dose of vecuronium is administered to facilitate endotracheal intubation. Which of the following best estimates the elimination half-life of vecuronium in this patient?



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Which of the following statements about vecuronium is false?



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Patients with which of the following conditions may experience resistance to vecuronium?



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Vecuronium - References

References

The efficacy and safety of sugammadex for reversing postoperative residual neuromuscular blockade in pediatric patients: A systematic review., Liu G,Wang R,Yan Y,Fan L,Xue J,Wang T,, Scientific reports, 2017 Jul 18     [PubMed]
Dilemmas in Anesthetic Management of a Patient with History of Anaphylaxis to Vecuronium., Agrawal N,Gogia AR,Dayal M,, Anesthesia, essays and researches, 2017 Apr-Jun     [PubMed]
Comparison of Effect of Ephedrine and Priming on the Onset Time of Vecuronium., Anandan K,Suseela I,Purayil HV,, Anesthesia, essays and researches, 2017 Apr-Jun     [PubMed]
Reversal of Vecuronium-induced Neuromuscular Blockade with Low-dose Sugammadex at Train-of-four Count of Four: A Randomized Controlled Trial., Asztalos L,Szabó-Maák Z,Gajdos A,Nemes R,Pongrácz A,Lengyel S,Fülesdi B,Tassonyi E,, Anesthesiology, 2017 Jun 21     [PubMed]
Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine., Lemmens HJ,El-Orbany MI,Berry J,Morte JB Jr,Martin G,, BMC anesthesiology, 2010 Sep 1     [PubMed]
Boulila C,Ben Abdallah S,Marincamp A,Coic V,Lauverjat R,Ericher N,Bougouin W,Mira JP,Cariou A,Geri G, Use of Neuromuscular Blockers During Therapeutic Hypothermia After Cardiac Arrest: A Nursing Protocol. Critical care nurse. 2016 Dec;     [PubMed]
Kim KS,Cheong MA,Jeon JW,Lee JH,Shim JC, The dose effect of ephedrine on the onset time of vecuronium. Anesthesia and analgesia. 2003 Apr;     [PubMed]
Iwasaki H,Igarashi M,Yamauchi M,Namiki A, The effect of cardiac output on the onset of neuromuscular block by vecuronium. Anaesthesia. 1995 Apr;     [PubMed]

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