What is rapid sequence induction?  

RSI involves the administration of an induction agent and a muscle relaxant in rapid succession to facilitate endotracheal intubation.By omitting masked ventilation, RSI enables the airway to be secured rapidly and minimises air entry into the stomach, which can increase the risk of gastric regurgitation and aspiration of stomach contents, explain Tessarolo et al.⁴ 

The incidence of regurgitation and aspiration has been found to be between 3% and 13% of intubations and increases with repeated intubation attempts and prolonged time to intubation. Successful intubation on the first attempt, known as first‐pass success, is, therefore, an important goal of RSI.⁴ 

During RSI, adequate intubation conditions are achieved within 60 seconds in 93% of the patients with propofol anaesthesia, and 96% of the patients with fentanyl/thiopental anaesthesia, following a dose of 1mg/kg rocuronium bromide.⁵   

Surgical relaxation with this dose approaches 60 minutes, at which time the neuromuscular blockade may be reversed when functional recovery is evident.⁵   

Following a dose of 0.6mg/kg rocuronium bromide, adequate intubation conditions are achieved within 60 seconds in 81% and 75% of the patients during a rapid sequence induction technique with propofol or fentanyl/thiopental, respectively.⁵  

Storage recommendations  

Manufacturers recommend that rocuronium bromide should ideally be stored in a refrigerator (2°C-8°C). However, the product can also be stored outside of a refrigerator at a temperature of up to 25°C for a maximum of 12 weeks, after which it should be discarded.^1,5  

They caution that the rocuronium bromide should not be placed back into the refrigerator once it has been kept outside, and the storage period must not exceed the shelf-life.¹  

In clinical practice, however, it is common to return sealed, unused rocuronium bromide vials to the refrigerator after a theatre list. Kim et al showed that compared to rocuronium bromide stored in a refrigerator, products stored at room temperature have unfavourable intubating conditions at 90 seconds after injection. Therefore, storage temperature has some influences on the efficacy of rocuronium.^1,2,6  

According to Vermeulen et al, delayed onset of and shortened duration of action have been observed with rocuronium bromide. So, is it possible that these variations in the onset of and duration of action are the result of reintroducing rocuronium bromide to the cold-chain?² 

To answer the question, Vermeulen et al investigated the molecular effects – if any – of reintroducing rocuronium bromide into the cold-chain. The team subjected rocuronium bromide to different clinically applicable storage and temperature scenarios, after which the compound was analysed for integrity and quantities of the active compound, including detection of possible degradation products, by mass spectrometry, and compared to cold chain control samples.²  

They found that there were no significant differences between any of the temperature exposure groups (18°C or 24°C) or between single or double exposures at these temperatures.²  

Furthermore, no statistically significant difference could be demonstrated between the two control groups (cold chain preserved and room temperature controlled) with testing done at weeks one and six.²  

However, week 12 analysis revealed a statistically significant result which translates to a 26µg/ml difference, which clinically would have no effect. Substantial results were obtained with a secondary exposure to air, which lead to a 20% decrease in rocuronium bromide concentration.² 

Conclusion 

The authors concluded that up to two breakages in the cold-chain with subsequent exposure to clinically applicable increased temperatures had no statistical effect on the molecular structure of rocuronium bromide. Furthermore, the study confirmed that rocuronium bromide may be stored at room temperature for up to 12 weeks without any significant deterioration.²  

They do caution that during clinical use of rocuronium bromide, the detrimental effect of air exposure to the molecular integrity of this compound should be taken into consideration – especially during long cases with repeated top-up dosing or in cases where dilutions are done in advance.²  

REFERENCES 

1. Professional information. Rocuronium 10 mg/ml solution for injection/infusion. https://www.medicines.org.uk/emc/product/553/smpc/print#COMPOSITION
2. Vermeulen D, Wooding M, Outhoff K, Dippenaar The effect of cold-chain reintroduction on the molecular integrity of rocuronium bromide. SAJAA, 2021.
3. Rocuronium bromide. 
4. Tessarolo E, Alkhouri H, Lelos N, et al. Review article: Effectiveness and risks of cricoid pressure during rapid sequence induction for endotracheal intubation in the emergency department: A systematic review. Emerg Med Australas, 2022.
5. Product Monograph. Rocuronium bromide. https://www.sandoz.ca/sites/www.sandoz.ca/files/Rocuronium%20Bromide%20Injection%20Product%20Monograph.pdf
6. Kim YB, Kwak HJ, Kim DH et al. Effect of Storage Temperature of Rocuronium on Intubating Condition and Clinical Duration after Low-dose Technique. KJA, 2007.