Sugammadex vs Neostigmine: How the Effective Use of Sugammadex Reduces Costs

Postoperative residual curarization (PORC) frequently occurs following anesthesia and may be associated with the development of pulmonary complications, such as labored breathing, hypoxemia, and aspiration pneumonia. It may also result in a postoperative reduction in muscle strength that can cause an increase in recovery time and a prolonged length of stay in the postoperative anesthesia care unit (PACU). Complete and rapid reversal of neuromuscular blockade after surgery is, therefore, considered to be a primary element of safety for the patient.¹

Sugammadex vs Neostigmine

The reversal of nondepolarizing neuromuscular blocking agents (NMBAs) has traditionally been achieved with the administration of acetylcholinesterase inhibitors, such as neostigmine. However, the use of these drugs is associated with certain limitations, including their limited use for deep neuromuscular block, unpredictable efficacy, indirect mechanisms of reversal, and undesirable autonomic responses, such as bradycardia, bronchospasm, and increased respiratory secretions. Atropine and glycopyrrolate are anticholinergic medications, which are used to prevent these adverse effects but may themselves be associated with an increased risk of cardiac arrhythmias, blurred vision, and sedation.^2,3

Sugammadex is a newer agent that can be used for the reversal of certain nondepolarizing neuromuscular blocking agents such as rocuronium and vecuronium. It is a modified gamma-cyclodextrin that acts as a selective relaxant-binding agent and does not interfere with the acetylcholinesterase receptor systems. Thus, unlike neostigmine, it is associated with a lower risk of muscarinic adverse effects. Increased patient safety, rapid and predictable reversal of any degree of neuromuscular blockade, and a more efficient utilization of healthcare resources are some of the reported clinical benefits of sugammadex.^4,5 Sugammadex is one of the most expensive drugs currently used in anesthesia practice, and its high cost is a major obstacle in its adoption as a standard neuromuscular reversal agent.⁶ However, some studies suggest that the effective and appropriate use of sugammadex may actually lead to a reduction in overall hospital costs.

Sugammadex: Cost-saving Strategies

A lower-than-recommended dosage of sugammadex is often administered in clinical practice and this under-dosing is usually driven by cost concerns. The administration of a lower dosage of sugammadex may produce an initial successful, but transient, reversal of neuromuscular blockade followed by a recurrence of the block. This leads to postoperative residual curarization in the PACU, with its associated pulmonary complications. The increased incidence of PORC in turn is responsible for an increased length of stay in the PACU, a reduction in the productivity of the PACU due to an increase in the peak number of patients, and an increase in the operating room holding time. All these factors ultimately lead to a significant increase in hospital costs.⁷ Moreover, mixing sugammadex with neostigmine for the reversal of neuromuscular blockade at a lower cost may result in neostigmine-induced depolarizing neuromuscular weakness, and is not recommended.⁸

On the other hand, it has been found that if administered in appropriate doses, sugammadex has the ability to reverse the neuromuscular blockade caused by rocuronium more rapidly and effectively as compared to neostigmine, particularly from deeper levels of blockade. This would have a net cost reduction effect by decreasing the operating room recovery time. A decreased duration of anesthesia not only improves recovery time for patients, it cuts costs by

• Saving the time spent on prolonged awakenings in the PACU
• Reducing the side effects associated with PORC
• Allowing smoother patient flow through the operating room

These indirect cost-saving measures can counterbalance the relatively high cost of sugammadex.

Selection of Reversal Agent and Appropriate Dosage

Quantitative NMT monitoring should always be used when neuromuscular blocking agents (NMBs) are administered until full recovery has been documented. Quantitative NMT monitoring can estimate the degree of neuromuscular blockade and can help decide whether sugammadex or neostigmine should be used for reversal. For instance, deep and intense neuromuscular blockade cannot be reversed by neostigmine but can be reliably reversed by sugammadex. Hence, the decision to use sugammadex or neostigmine must preferably be guided by quantitative NMT monitoring. Moreover, the appropriate dose of the reversal agent that is required to reverse the neuromuscular blockade depends directly on the concentration of the neuromuscular blocking agent as well as the depth of neuromuscular blockade. Thus, the dose recommendations for the reversal agent, whether sugammadex or neostigmine, should also be decided on the basis of the values obtained by neuromuscular transmission monitoring.^7,9

Stimpod NMS450X – Detection of the Depth of Neuromuscular Blockade

The Stimpod NMS450X is a quantitative neuromuscular monitor that automatically monitors entire cases from electrode placement all the way through to extubation, thanks to OneTouch NMT^TM technology. The Stimpod supports all stimulation modes, including Train-of-Four (TOF), Post-Tetanic Count (PTC), Tetanus and Twitch Stimulation, as well as Double Burst (DB) to provide accurate, real-time NMT monitoring. It can detect the depth of neuromuscular blockade through the entire surgical procedure and can automatically reinitiate TOF monitoring as the reversal process begins.

The Stimpod NMS450X’s auto mode will automatically alter the stimulation mode based on the depth of the neuromuscular block. The following depth-of-block zones are displayed on screen for quick referencing during procedures:

• Profound – PTC of zero
• Deep – PTC of 1 to 3
• Moderate – TOF count of 1 to 3
• Shallow – TOF ratio < 40%
• Minimal – TOF ratio 40%-90%
• Recovered – TOF ratio > 90%

The above mentioned depth-of-block zones visualized on the Stimpod NMT monitor can provide an accurate assessment of the degree of neuromuscular blockade, which can then be used to make the selection between sugammadex and neostigmine for the reversal of blockade. These depth-of-block zones can also be used to determine the optimal titration of the reversal agent required to fully recover the patient. The following table depicts the optimal titration of sugammadex and neostigmine based on the degree of neuromuscular blockade.

Depth of Neuromuscular Blockade	Optimal Titration
Profound block (PTC of zero)	16 mg/kg Sugammadex
Deep block (PTC of 1 to 3)	4 mg/kg Sugammadex
Moderate block (TOF count of 1 to 3)	2 mg/kg Sugammadex
Shallow block (TOF ratio < 40%)	50-70 µg/kg Neostigmine
Minimal block (TOF ratio 40%-90%)	20-30 µg/kg Neostigmine

Optimal titration based on depth of neuromuscular blockade ^10,11

Therefore, the Stimpod quantitative neuromuscular monitor is an effective cost-saving device that can help the anesthesiologist in choosing the right reversal agent as well as its correct dosage. It’s an indispensable tool to optimize hospital costs while ensuring that patients receive the best postoperative care.

References

1. Butterly A, Bittner EA, George E, Sandberg WS, Eikermann M, Schmidt U. Postoperative residual curarization from intermediate-acting neuromuscular blocking agents delays recovery room discharge. Br J Anaesth 2010; 105: 304–9.
2. Luo J, Chen S, Min S, Peng L. Reevaluation and update on efficacy and safety of neostigmine for reversal of neuromuscular blockade. Ther Clin Risk Manag. 2018;14:2397–2406. Published 2018 Dec 10. doi:10.2147/TCRM.S179420
3. Kent NB, Liang SS, Phillips S, et al. Therapeutic doses of neostigmine, depolarising neuromuscular blockade and muscle weakness in awake volunteers; A double-blind, placebo controlled, randomised volunteer study. Anaesthesia 2018; 73: 1079–90.
4. Nag K, Singh DR, Shetti AN, Kumar H, Sivashanmugam T, Parthasarathy S. Sugammadex: A revolutionary drug in neuromuscular pharmacology. Anesth Essays Res. 2013;7(3):302–306. doi:10.4103/0259-1162.123211
5. Cada DJ, Levien TL, Baker DE. Sugammadex. Hosp Pharm. 2016;51(7):585–596. doi:10.1310/hpj5107-585
6. O’Reilly-Shah VN, Wolf FA, Jabaley CS, Lynde GC. Using a worldwide in-app survey to explore sugammadex usage patterns: a prospective observational study. Br J Anaesth. 2017;119:333–5. https://doi.org/10.1093/bja/aex171
7. de Boer HD, Carlos RV, Brull SJ. Is lower-dose sugammadex a cost-saving strategy for reversal of deep neuromuscular block? Facts and fiction. BMC Anesthesiol. 2018 Nov 06;18(1):159.
8. Aouad MT, Alfahel WS, Kaddoum RN, Siddik-Sayyid SM. Half dose sugammadex combined with neostigmine is non-inferior to full dose sugammadex for reversal of rocuronium-induced deep neuromuscular blockade: a cost-saving strategy. BMC Anesthesiol. 2017;17(1):57. Published 2017 Apr 11. doi:10.1186/s12871-017-0348-9
9. Cammu G. Sugammadex: Appropriate Use in the Context of Budgetary Constraints. Curr Anesthesiol Rep. 2018;8(2):178–185. doi:10.1007/s40140-018-0265-6
10. Butterly A, Bittner EA, George E, Sandberg WS, Eikermann M, Schmidt U, Postoperative residual curarization from intermediate-acting neuromuscular blocking agents delays recovery room discharge. Br J Anaesth 2010; 105: 304-9.
11. Bridion (Sugammadex) dosage and administration. Merck Connect. https://www.merckconnect.com/bridion/dosing-administration/

Contributors

Roche Janse van Rensburg, Maruschka van der Bank, Lourie Höll

Enquiries

Maruschka van der Bank
Product Specialist
maruschka@xavant.com