Anesthesia

Question 1

What is the class and MOA of Rocuronium?

What is the intubating dose?

What is the reversal agent? Dose?

Which has a faster onset of action, rocuronium or succinylcholine?

Contraindications of succinylcholine?

Which nondepolarizing muscle relaxer is metabolized by Hoffman degradation?

Answer 1

Concise Answer
Rocuronium is a non-depolarizing neuromuscular blocking agent. The dosing for rocuronium varies based on the clinical scenario:
* Intubation: 0.45–0.9 mg/kg IV or 0.6 mg/kg IV bolus.
* Rapid Sequence Intubation (RSI): 0.6–1.2 mg/kg IV bolus.
* Maintenance: 0.15 mg/kg boluses.
* Precurarization prior to succinylcholine: 0.1 mg/kg.
* Pediatric laryngospasm: 1 to 2 mg/kg.

Summary
Rocuronium is a widely used non-depolarizing muscle relaxant. It acts by competitively binding to acetylcholine receptors at the neuromuscular junction, preventing depolarization. Rocuronium is favored for its relatively rapid onset of action compared to other non-depolarizing agents. Sugammadex is available to reverse its effects.

Context / Supporting information / Comprehensive review

Class and Mechanism of Action
Rocuronium is classified as a non-depolarizing neuromuscular blocking agent. These agents work by competitively antagonizing acetylcholine (ACh) at the postjunctional membrane of the neuromuscular junction. This prevents ACh from binding to its receptors, inhibiting depolarization and subsequent muscle contraction. Rocuronium, in particular, is a monoquaternary steroid analogue of vecuronium, designed to have a rapid onset of action.

Dosing of Rocuronium
1. Intubation Dose:
* The typical intubation dose is 0.45 to 0.9 mg/kg intravenously.
* Some sources specify a dose of 0.6 mg/kg IV bolus for intubation.
* For intramuscular use (e.g., in infants), a dose of 1 mg/kg provides adequate vocal cord and diaphragmatic paralysis, though onset may take 3 to 6 minutes. In children, the IM dose is 2 mg/kg.
2. Rapid Sequence Intubation (RSI):
* For RSI, a higher dose of 0.6 to 1.2 mg/kg IV bolus is recommended to achieve rapid paralysis.
* A dose of 1 mg/kg IV is also mentioned for RSI.
* To achieve an onset similar to succinylcholine, a higher dose of 1.2 mg/kg can be used, though this prolongs the duration of action.
3. Maintenance Dose:
* Maintenance of muscle relaxation during longer procedures can be achieved with intermittent boluses of 0.15 mg/kg.
* Alternatively, a continuous infusion of 5 to 12 mcg/kg/min can be used.
4. Precurarization:
* Rocuronium can be used at a dose of 0.1 mg/kg for precurarization prior to succinylcholine administration to reduce fasciculations and postoperative myalgias.
5. Laryngospasm:
* For the treatment of laryngospasm, a dose of 0.1 to 0.5 mg/kg IV or 4 to 6 mg/kg IM can be used.

Pharmacokinetics
* Onset: Rocuronium has a rapid onset of action compared to other non-depolarizing agents. At higher doses (0.9–1.2 mg/kg), its onset approaches that of succinylcholine (60–90 seconds).
* Duration: The duration of action for rocuronium at a normal intubating dose (0.6 mg/kg) is 35 to 50 minutes. Increasing the dose to 1.2 mg/kg can extend the duration to approximately 70 minutes.
* Metabolism and Excretion: Rocuronium undergoes minimal metabolism and is primarily eliminated by the liver and, to a lesser extent, by the kidneys. Severe liver failure and pregnancy can modestly prolong its duration of action.

Clinical Considerations and Advantages
1. Advantages:
* Rapid Onset: Its relatively rapid onset makes it a suitable alternative to succinylcholine for RSI when succinylcholine is contraindicated.
* Lack of Significant Side Effects: Rocuronium does not cause hyperkalemia or myalgia. It also does not trigger malignant hyperthermia.
* Reversal: The availability of sugammadex allows for rapid reversal of rocuronium-induced neuromuscular blockade.
2. Use in Specific Conditions:
* Liver Disease: Initial dosage requirements may be increased in patients with advanced liver disease due to a larger volume of distribution. However, severe liver failure can prolong its duration of action.
* Renal Disease: The duration of action is not significantly affected by renal disease.
* Older Adults: Older adult patients may experience a prolonged duration of action due to decreased liver mass.

Sugammadex for Reversal
Sugammadex is a selective relaxant-binding agent used to reverse neuromuscular blockade induced by rocuronium (and vecuronium).
* Mechanism: Sugammadex encapsulates rocuronium molecules, preventing them from binding to acetylcholine receptors.
* Dosage:
* For immediate reversal after intubation, a dose of 16 mg/kg is recommended.
* For deep paralysis, the dose is 4 mg/kg; for moderate paralysis, it is 2 mg/kg.
* Reversal typically occurs within 2-3 minutes.
* Considerations: Sugammadex is primarily eliminated unchanged via the kidneys and is not recommended for patients with severe kidney dysfunction (creatinine clearance <30 mL/min).

Succinylcholine vs. Rocuronium
Succinylcholine has historically been the primary agent for rapid sequence intubation. However, rocuronium is a viable alternative, especially when succinylcholine is contraindicated.

• Onset: Succinylcholine has a slightly faster onset of action (30-60 seconds) compared to rocuronium (60-90 seconds), although this discrepancy can be minimized by using a higher dose of rocuronium (1.2 mg/kg).
• Duration: Succinylcholine has an ultra-short duration of action (5-10 minutes), whereas rocuronium’s effects last longer (35-50 minutes) unless reversed with sugammadex.
• Contraindications: Succinylcholine has several contraindications, including hyperkalemia, recent burns or crush injuries, neuromuscular disorders, and malignant hyperthermia. Rocuronium has fewer contraindications, mainly a known allergy to the drug.

Other Non-Depolarizing Agents
Other non-depolarizing agents like vecuronium, atracurium, and cisatracurium are available, but rocuronium is often preferred for its more rapid onset. Cisatracurium is notable for its degradation via Hoffman elimination, making it suitable for patients with renal or hepatic failure.

By understanding the class, dosing, pharmacokinetics, and clinical considerations of rocuronium, practitioners can effectively use this neuromuscular blocking agent in various clinical scenarios, particularly when rapid sequence intubation is required and succinylcholine is not suitable. The availability of sugammadex further enhances its safety and utility by allowing for rapid reversal of its effects.