Depolarizing Neuromuscular Blocking Drugs


Article Author:
Michael Gulenay


Article Editor:
Josephin Mathai


Editors In Chief:
Chaddie Doerr


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes
Kavin Sugumar


Updated:
10/27/2018 12:31:31 PM

Indications

Neuromuscular blocking agents are commonly used to paralyze patients requiring intubation whether in an emergency as a life-saving intervention or for a scheduled surgery and procedure. The indications for intubation during an emergency can be divided into 3 categories: failure to maintain or protect the airway, failure to adequately ventilate or oxygenate, and anticipation of a decline in clinical status. 

Pharmacologic paralysis is a vital aspect of rapid sequence intubation (RSI) and serves to both improve visualization of the glottic anatomy and to prevent vomiting during the intubation attempt. Importantly, the conjunctive use of induction agents is vital to RSI to reduce the sympathetic reflexes, improve intubating conditions, and avoid the unwarranted effect of paralyzing a conscious patient.

The most well-known depolarizing neuromuscular blocking agent is succinylcholine. It is the only such drug used clinically and is considered by many the drug of choice for emergency department RSI although this is controversial. It provides the fastest of optimal conditions during intubation of critically ill patients.

Mechanism of Action

There are 2 types of neuromuscular blocking agents that work at the neuromuscular junction: depolarizing and non-depolarizing. Depolarizing muscle relaxants act as acetylcholine (ACh) receptor agonists by binding to the ACh receptors of the motor end plate and generating an action potential. However, they are resistant to and not metabolized by acetylcholinesterase leading to persistent depolarization of the muscle fibers, thus resulting in the well-recognized muscle fasciculations and paralysis of the patient. This is in contrast to non-depolarizing muscle relaxants, which act as competitive antagonists. They bind (ACh) receptors but do not produce an action potential. Thus, they prevent ACh from binding and as a result neural end plate potentials do not develop.[1][2]

After a depolarizing agent binds to the motor end plate receptor the agent remains bound and thus the end plate cannot repolarize. This is also known as a phase I block. It is during this depolarizing phase that the transient muscle fasciculation occur. After adequate depolarization has occurred, phase II (desensitizing phase) sets in and the muscles are no longer receptive to acetylcholine released by the motor neurons. It is at this point that the depolarizing agent has fully achieved paralysis.[2]

It is also important to recognize that these muscles relaxants do not only target nicotinic receptors but also muscarinic receptors.[3] The classical depolarizing blocking drug is succinylcholine. It has a rapid onset (30 seconds) and a short duration of action (approximately 6 minutes), because of the degradation by various cholinesterases.[2]

Adverse Effects

Since these drugs cause paralysis of the diaphragm, mechanical ventilation should be at hand to provide respiratory support. In addition, these drugs may produce cardiovascular effects including dysrhythmias since they have effects on muscarinic receptors.[3] When nicotinic receptors of the autonomic ganglia or adrenal medulla are blocked, these drugs cause autonomic symptoms. In addition, neuromuscular blockers result in a histamine release leading to hypotension, flushing, and tachycardia.[3] The depolarizing effect on the muscles fibers may momentarily release a large amount of potassium. This places the patient at risk for life-threatening complications such as hyperkalemia and cardiac arrhythmias.[2][3]

More Adverse Effects[2][3]

  • Muscle fasciculation which may result in postoperative pain
  • Jaw rigidity
  • Apnea
  • Respiratory depression
  • Bradycardia
  • Hypotension
  • Sinus tachycardia
  • Increased IOP
  • Excessive salivation
  • Hypersensitivity reactions
  • Malignant hyperthermia
  • Myoglobinuria/myoglobinemia

Contraindications

As mentioned above, depolarizing muscle agents bind to all acetylcholine receptors of the autonomic nervous system and when targeting cardiac muscarinic receptors patients may develop bradycardia, especially in repeat doses. There is a relative contraindication in a patient with bradycardia. In addition, the defasciculations not only result in a large amount of potassium release but also oxygen depletion.[3]

Depolarizing muscle agents are contraindicated in cases of neurologic injury; such as a cerebral vascular accident or spinal cord injury; or severe tissue injury including trauma or burns. This results from post-synaptic receptor up-regulation that typically occurs within three to five days. These injuries place the patient at risk for life-threatening hyperkalemia. Of note, the risk of hyperkalemia is not associated with decreased potassium clearance however attention should be given to those who have chronically elevated potassium levels such as renal failure patients.[3]

Depolarizing agents are absolutely contraindicated in patients with degenerative neuromuscular disorders or a history of malignant hyperthermia. Undiagnosed children with skeletal muscle myopathy, such as Duchenne's muscular dystrophy, are at risk for rhabdomyolysis with hyperkalemia.[3][4] This is subsequently followed by ventricular dysrhythmias, cardiac arrest, and death. It occurs soon after administration and requires immediate treatment of hyperkalemia. In children, it is reserved for emergency intubation or in instances when securing of the airway is immediately necessary.

Other Contraindications[2][3]

  • Hypersensitivity to drug
  • Malignant hyperthermia
  • Lack of ventilatory support
  • Ocular surgery, Penetrating eye injuries, Closed-angle glaucoma 
  • Disorders of plasma pseudocholinesterase - Patients with atypical or deficient pseudocholinesterase will have prolonged paralysis
  • Myopathies associated with elevated serum creatine kinase
  • Extensive denervation of skeletal muscle or upper motor neuron injury

Monitoring

The proper precautions are necessary because of the potential severity of these agents. The immediate availability of appropriate emergency treatment is unquestionable. These agents should be administered by trained personnel with a facility equipped to monitor, assist, and control respiration.

Toxicity

Malignant hyperthermia is a life-threatening clinical syndrome of hypermetabolism involving the skeletal muscle. It is triggered in susceptible individuals primarily by inhalational anesthetic agents and the muscle relaxant succinylcholine although other drugs have also been considered as potential triggers. It is not an allergy but an inherited disorder. A typical presentation involves tachycardia, dysrhythmias, rigidity, rapidly increasing temperature, hyperkalemia, sympathetic hyperactivity, disseminated intravascular coagulopathy (DIC), and multi-organ failure.[5] Dantrolene is the primary drug used for the treatment and prevention of malignant hyperthermia.[6]

Enhancing Healthcare Team Outcomes

Several controversies persist regarding RSI. The most prominent debate centers on the use of rocuronium versus succinylcholine for standard RSI paralysis. Advocates of rocuronium cite its lack of contraindications and avoidance of depolarization in the middle of an intubation attempt. Advocates for succinylcholine argue for its rapid onset and rapid recovery time thought to be potentially helpful in a critically ill patient who is difficult to intubate and oxygenate. One of the main differences between these two types of neuromuscular-blocking drugs is in their reversal and pharmacokinetics. Acetylcholinesterase inhibitor drugs reverse non-depolarizing blockers since they are competitive antagonists at the ACh receptor site and thus, reverse by increasing in ACh. On the other hand, the depolarizing blockers are more resistant to acetylcholinesterase resulting in a prolonged effect under the administration of acetylcholinesterase inhibitors. The argument is mostly academic. Both agents are excellent, and when dosed properly, result in comparable intubating conditions.[7][8]


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Depolarizing Neuromuscular Blocking Drugs - Questions

Take a quiz of the questions on this article.

Take Quiz
What drug is used for rapid intubation at the bedside because it is a fast acting depolarizing agent and quickly achieves optimal conditions for intubation?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which neuromuscular blocking agent works by depolarization?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Depolarizing muscular blocking drugs have numerous contraindications. Which of the following conditions does not place the patient at risk for life-threatening hyperkalemia upon initial presentation to the emergency department?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
When is neuromuscular paralysis fully achieved with depolarizing muscular blocking agents?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Depolarizing Neuromuscular Blocking Drugs - References

References

Do we foresee new emerging drugs to treat malignant hyperthermia?, Just KS,Gerbershagen MU,Grensemann J,Wappler F,, Expert opinion on emerging drugs, 2015 Jun     [PubMed]
Malignant hyperthermia: pharmacology of triggering., Hopkins PM,, British journal of anaesthesia, 2011 Jul     [PubMed]
Rocuronium vs. succinylcholine in the emergency department: a critical appraisal., Mallon WK,Keim SM,Shoenberger JM,Walls RM,, The Journal of emergency medicine, 2009 Aug     [PubMed]
D'Souza RS,Johnson RL, Nondepolarizing Paralytics null. 2018 Jan     [PubMed]
Hager HH,Burns B, Depolarizing Muscle Relaxants, Succinylcholine Chloride null. 2018 Jan     [PubMed]
Tran DTT,Newton EK,Mount VAH,Lee JS,Mansour C,Wells GA,Perry JJ, Rocuronium vs. succinylcholine for rapid sequence intubation: a Cochrane systematic review. Anaesthesia. 2017 Jun     [PubMed]
Naguib M,Magboul MM, Adverse effects of neuromuscular blockers and their antagonists. Middle East journal of anaesthesiology. 1998 Jun     [PubMed]
Barrons RW,Nguyen LT, Succinylcholine-Induced Rhabdomyolysis in Adults: Case Report and Review of the Literature. Journal of pharmacy practice. 2018 Aug 29     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Anesthesia Technician. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Anesthesia Technician, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Anesthesia Technician, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Anesthesia Technician. When it is time for the Anesthesia Technician board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Anesthesia Technician.