Eur J Anaesthesiol 2013; 30:583–584
INVITED COMMENTARY
The never ending story or the search for a nondepolarising alternative to succinylcholine Thomas Fuchs-Buder and Denis Schmartz
European Journal of Anaesthesiology 2013, 30:583–584
This Invited Commentary is part of a Pro and Con debate and is accompanied by the following articles: Girard T. Pro: rocuronium should replace succinylcholine for rapid sequence induction. Eur J Anaesthesiol 2013; 30:585–589. Schreiber J-U. Con: succinylcholine should not be replaced by rocuronium for rapid sequence induction. Eur J Anaesthesiol 2013; 30:590–593.
Rapid sequence induction (RSI) is an established method of inducing anaesthesia in patients at risk of pulmonary aspiration and allowing rapid intubation of the trachea. Initially, it involves loss of consciousness, application of cricoid pressure followed by tracheal intubation without face mask ventilation. The ideal characteristics of a neuromuscular blocking agent for RSI comprise a rapid onset to minimise the risk of aspiration, a predictably rapid recovery to facilitate the return of ventilation if intubation fails and minimal haemodynamic and systemic effects.1 Succinylcholine does have a rapid onset and offset of action, but there are many side effects associated with succinylcholine, some of which are life-threatening. To be considered as a true alternative for RSI, rocuronium should provide both a fast onset of action and a predictably rapid offset of action. The onset and peak effect of rocuronium are both dose-dependent. Although the normal intubating dose of this compound, 0.6 mg kg 1 (2 ED95), is clearly inappropriate for RSI, larger doses of rocuronium have been proposed in this context.2,3 Kirkegaard-Nielsen et al.4 reported that 1.04 mg kg 1 of rocuronium is needed for a 95% probability of successful intubation at 60 s, that
is start of intubation 40 s after rocuronium and the tracheal tube passed through the patient’s vocal cords and the cuff inflated within the following 20 s. Of interest in this context are the findings of a Cochrane review published by Perry et al.5 in 2008. The authors combined the results of 37 studies with a total of 2690 patients and concluded that rocuronium is less effective than succinylcholine for creating excellent intubation conditions for RSI. However, 30 of the 37 studies compared succinylcholine with rocuronium 0.6 to 0.7 mg kg 1, clearly an inappropriate dose for RSI. In a subgroup of 1009 patients, succinylcholine was compared with rocuronium 0.9 to 1.0 or 1.2 mg kg 1, 1, corresponding to the current dosing recommendations in the context of RSI. In this relevant subgroup, Perry et al.5 further confirmed no statistically significant difference in intubating conditions compared with succinylcholine. This may explain why rocuronium is currently the most popular nondepolarising alternative to succinylcholine for RSI.6,7 Of interest in this context, in a recent nationwide survey of the management of RSI, 40% of respondents never or rarely used succinylcholine for RSI and 30% mostly or always used rocuronium.8 Thus, there is convincing evidence that high-dose rocuronium offers comparable intubating conditions to those obtained after succinylcholine. However, increasing the dose of rocuronium also increases its duration of action. At doses of 1.0 to 1.2 mg kg 1, the time to spontaneous recovery to a train-of-four (TOF) ratio of 0.9 is around 2 h, which is much too long to allow return of ventilation if intubation fails. This is why the authors of the 2008 Cochrane review concluded that succinylcholine was clinically superior for RSI than for rocuronium because it has a shorter duration of action. In 2009, a new player came on stage; sugammadex, a specific reversal agent for rocuronium, became available.
From the CHU de Nancy, Institut lorrain du coeur et des vaisseaux Louis Mathieu, Rue du Morvan, Vandoeuvre-le`s-Nancy, France Correspondence to Dr Thomas Fuchs-Buder, CHU de Nancy, Institut lorrain du coeur et des vaisseaux Louis Mathieu, Rue du Morvan, 54511 Vandoeuvre-le`s-Nancy, France Tel: +33 383 153942; e-mail: [email protected] 0265-0215 ß 2013 Copyright European Society of Anaesthesiology
DOI:10.1097/EJA.0b013e32836315c3
Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
584 Fuchs-Buder and Schmartz
In contrast with neostigmine, no minimum prereversal degree of recovery is required before administration; it has been shown that rocuronium-induced neuromuscular block can be fully reversed within 2 to 3 min with 2 mg kg 1 of sugammadex.9 Pu¨hringer et al.10 expanded this concept to immediate reversal after high-dose rocuronium. When sugammadex 8, 12 or 16 mg kg 1 was given 3 min after rocuronium 1.2 mg kg 1, the median times to a TOF ratio of 0.9 were 2.2, 1.3 and 1.9 min, respectively. These data suggest that the time course of action of the combination of high-dose rocuronium (1.0 to 1.2 mg kg 1) and early administration of sugammadex 8 to 16 mg kg 1 could potentially challenge the spontaneous recovery time after succinylcholine 1.0 mg kg 1. This hypothesis was recently tested by Sorensen et al.11 They reported that recovery of neuromuscular function was faster after rocuronium 1 mg kg 1 followed by sugammadex 16 mg kg 1 than spontaneous recovery after succinylcholine 1 mg kg 1. The time from tracheal intubation to a T1 recovery of 90% was 518 s after succinylcholine and 168 s after rocuronium/sugammadex. However, neuromuscular recovery may be considered as a surrogate endpoint; re-establishment of spontaneous ventilation is the relevant criterion in this context. This also occurred significantly earlier using rocuroniumsugammadex (216 compared with 406 s after succinylcholine). These data highlight the potential of rocuronium/ sugammadex in the RSI setting, especially in patients with poor apnoea tolerance, such as those undergoing caesarean section or bariatric surgery. However, although recovery after succinylcholine occurs spontaneously, sugammadex must be administered to facilitate recovery from rocuronium-induced neuromuscular block. Thus, whether rocuronium/sugammadex really saves a patient in a ‘cannot intubate – cannot ventilate’ situation depends also on logistical and organisational factors, such as drug availability and preparation. Bisschops et al.12 assessed this point in a manikin-based simulation of failed RSI. In their setting, it took 6.7 min to prepare and administer an appropriate dose of sugammadex. To avoid such a delayed administration in a real-case scenario, sugammadex should be available within the operating theatre when high-dose rocuronium is used for RSI, the anaesthesia team should be trained in its use, each patient’s individual sugammadex dose requirements should be determined in advance and 500-mg vials rather than 200-mg vials of the compound should be kept in readiness. The search for a nondepolarising alternative to succinylcholine has lasted for several decades and the ‘end’ of
succinylcholine has been announced several times. However, these predictions have had to be revised regularly and succinylcholine is still alive! Increasing evidence now suggests that rocuronium/sugammadex could be considered as the first serious nondepolarising challenger to succinylcholine in the RSI context. The latest arguments in that controversy are discussed in the Pro-Con debate published in the present issue of the European Journal of Anaesthesiology.13,14. This could be the last chapter of a never ending story, at least for a while!
Acknowledgements Assistance with the invited commentary: none declared. Financial support and sponsorship: none declared. Conflicts of interest: TFB has received payments for lectures from Merck. Comment from the Editor: this invited commentary was checked and accepted by the editors but was not sent for external peer review.
References 1 2
3
4
5
6 7
8
9
10
11
12
13 14
Sinclair RCF, Luxton MC. Rapid sequence induction. Cont Educ Anaesth Crit Care Pain 2005; 5:45–48. Engbaek J, Viby-Mogensen J. Can rocuronium replace succinylcholine in a rapid-sequence induction of anaesthesia? Acta Anaesthesiol Scand 1999; 43:1–3. Fuchs-Buder T, Tassonyi E. Intubating conditions and time course of rocuronium-induced neuromuscular block in children. Br J Anaesth 1996; 77:335–338. Kirkegaard-Nielsen H, Caldwell J, Berry P. Rapid tracheal intubation with rocuronium: a probability approach to determining dose. Anesthesiology 1999; 91:31–36. Perry JJ, Lee JS, Sillberg VA, Wells GA. Rocuronium versus succinylcholine for rapid sequence induction intubation. Cochrane Database Syst Rev 2008;CD002788. Morris J, Cook TM. Rapid sequence induction: a national survey of practice. Anaesthesia 2001; 56:1090–1096. Fink H, Geldner G, Fuchs-Buder T, et al. Muscle relaxants in Germany 2005. A comparison of application customs in hospitals and private practices. Anaesthesist 2006; 55:668–678. Rohsbach CB, Wirth SO, Lenz K, Priebe HJ. Survey of the current management of rapid sequence induction (RSI) in Germany. Minerva Anestesiologica 2013; [Epub ahead of print]. Blobner M, Eriksson LI, Scholz J, et al. Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial. Eur J Anaesthesiol 2010; 27:874–881. Pu¨hringer FK, Rex C, Sielenka¨mper AW, et al. Reversal of profound, highdose rocuronium-induced neuromuscular blockade by sugammadex at two different time points. An international, multicenter, randomized, dosefinding, safety assessor-blinded, phase II trial. Anesthesiology 2008; 109:188–197. Sorensen MK, Bretlau C, Ga¨tke MR, et al. Rapid sequence induction and intubation with rocuronium-sugammadex compared with succinylcholine: a randomised trial. Br J Anaesth 2012; 108:682–689. Bisschops MMA, Holleman C, Huitink JM. Can sugammadex save a patient in a simulated ‘cannot intubate, cannot ventilate’ situation? Anaesthesia 2010; 65:936–941. Girard T. Pro: rocuronium should replace succinylcholine for rapid sequence induction. Eur J Anaesthesiol 2013; 30:585–589. Schreiber J-U. Con: succinylcholine should not be replaced by rocuronium for rapid sequence induction. Eur J Anaesthesiol 2013; 30:590–593.
Eur J Anaesthesiol 2013; 30:583–584 Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
INVITED COMMENTARY
The never ending story or the search for a nondepolarising alternative to succinylcholine Thomas Fuchs-Buder and Denis Schmartz
European Journal of Anaesthesiology 2013, 30:583–584
This Invited Commentary is part of a Pro and Con debate and is accompanied by the following articles: Girard T. Pro: rocuronium should replace succinylcholine for rapid sequence induction. Eur J Anaesthesiol 2013; 30:585–589. Schreiber J-U. Con: succinylcholine should not be replaced by rocuronium for rapid sequence induction. Eur J Anaesthesiol 2013; 30:590–593.
Rapid sequence induction (RSI) is an established method of inducing anaesthesia in patients at risk of pulmonary aspiration and allowing rapid intubation of the trachea. Initially, it involves loss of consciousness, application of cricoid pressure followed by tracheal intubation without face mask ventilation. The ideal characteristics of a neuromuscular blocking agent for RSI comprise a rapid onset to minimise the risk of aspiration, a predictably rapid recovery to facilitate the return of ventilation if intubation fails and minimal haemodynamic and systemic effects.1 Succinylcholine does have a rapid onset and offset of action, but there are many side effects associated with succinylcholine, some of which are life-threatening. To be considered as a true alternative for RSI, rocuronium should provide both a fast onset of action and a predictably rapid offset of action. The onset and peak effect of rocuronium are both dose-dependent. Although the normal intubating dose of this compound, 0.6 mg kg 1 (2 ED95), is clearly inappropriate for RSI, larger doses of rocuronium have been proposed in this context.2,3 Kirkegaard-Nielsen et al.4 reported that 1.04 mg kg 1 of rocuronium is needed for a 95% probability of successful intubation at 60 s, that
is start of intubation 40 s after rocuronium and the tracheal tube passed through the patient’s vocal cords and the cuff inflated within the following 20 s. Of interest in this context are the findings of a Cochrane review published by Perry et al.5 in 2008. The authors combined the results of 37 studies with a total of 2690 patients and concluded that rocuronium is less effective than succinylcholine for creating excellent intubation conditions for RSI. However, 30 of the 37 studies compared succinylcholine with rocuronium 0.6 to 0.7 mg kg 1, clearly an inappropriate dose for RSI. In a subgroup of 1009 patients, succinylcholine was compared with rocuronium 0.9 to 1.0 or 1.2 mg kg 1, 1, corresponding to the current dosing recommendations in the context of RSI. In this relevant subgroup, Perry et al.5 further confirmed no statistically significant difference in intubating conditions compared with succinylcholine. This may explain why rocuronium is currently the most popular nondepolarising alternative to succinylcholine for RSI.6,7 Of interest in this context, in a recent nationwide survey of the management of RSI, 40% of respondents never or rarely used succinylcholine for RSI and 30% mostly or always used rocuronium.8 Thus, there is convincing evidence that high-dose rocuronium offers comparable intubating conditions to those obtained after succinylcholine. However, increasing the dose of rocuronium also increases its duration of action. At doses of 1.0 to 1.2 mg kg 1, the time to spontaneous recovery to a train-of-four (TOF) ratio of 0.9 is around 2 h, which is much too long to allow return of ventilation if intubation fails. This is why the authors of the 2008 Cochrane review concluded that succinylcholine was clinically superior for RSI than for rocuronium because it has a shorter duration of action. In 2009, a new player came on stage; sugammadex, a specific reversal agent for rocuronium, became available.
From the CHU de Nancy, Institut lorrain du coeur et des vaisseaux Louis Mathieu, Rue du Morvan, Vandoeuvre-le`s-Nancy, France Correspondence to Dr Thomas Fuchs-Buder, CHU de Nancy, Institut lorrain du coeur et des vaisseaux Louis Mathieu, Rue du Morvan, 54511 Vandoeuvre-le`s-Nancy, France Tel: +33 383 153942; e-mail: [email protected] 0265-0215 ß 2013 Copyright European Society of Anaesthesiology
DOI:10.1097/EJA.0b013e32836315c3
Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
584 Fuchs-Buder and Schmartz
In contrast with neostigmine, no minimum prereversal degree of recovery is required before administration; it has been shown that rocuronium-induced neuromuscular block can be fully reversed within 2 to 3 min with 2 mg kg 1 of sugammadex.9 Pu¨hringer et al.10 expanded this concept to immediate reversal after high-dose rocuronium. When sugammadex 8, 12 or 16 mg kg 1 was given 3 min after rocuronium 1.2 mg kg 1, the median times to a TOF ratio of 0.9 were 2.2, 1.3 and 1.9 min, respectively. These data suggest that the time course of action of the combination of high-dose rocuronium (1.0 to 1.2 mg kg 1) and early administration of sugammadex 8 to 16 mg kg 1 could potentially challenge the spontaneous recovery time after succinylcholine 1.0 mg kg 1. This hypothesis was recently tested by Sorensen et al.11 They reported that recovery of neuromuscular function was faster after rocuronium 1 mg kg 1 followed by sugammadex 16 mg kg 1 than spontaneous recovery after succinylcholine 1 mg kg 1. The time from tracheal intubation to a T1 recovery of 90% was 518 s after succinylcholine and 168 s after rocuronium/sugammadex. However, neuromuscular recovery may be considered as a surrogate endpoint; re-establishment of spontaneous ventilation is the relevant criterion in this context. This also occurred significantly earlier using rocuroniumsugammadex (216 compared with 406 s after succinylcholine). These data highlight the potential of rocuronium/ sugammadex in the RSI setting, especially in patients with poor apnoea tolerance, such as those undergoing caesarean section or bariatric surgery. However, although recovery after succinylcholine occurs spontaneously, sugammadex must be administered to facilitate recovery from rocuronium-induced neuromuscular block. Thus, whether rocuronium/sugammadex really saves a patient in a ‘cannot intubate – cannot ventilate’ situation depends also on logistical and organisational factors, such as drug availability and preparation. Bisschops et al.12 assessed this point in a manikin-based simulation of failed RSI. In their setting, it took 6.7 min to prepare and administer an appropriate dose of sugammadex. To avoid such a delayed administration in a real-case scenario, sugammadex should be available within the operating theatre when high-dose rocuronium is used for RSI, the anaesthesia team should be trained in its use, each patient’s individual sugammadex dose requirements should be determined in advance and 500-mg vials rather than 200-mg vials of the compound should be kept in readiness. The search for a nondepolarising alternative to succinylcholine has lasted for several decades and the ‘end’ of
succinylcholine has been announced several times. However, these predictions have had to be revised regularly and succinylcholine is still alive! Increasing evidence now suggests that rocuronium/sugammadex could be considered as the first serious nondepolarising challenger to succinylcholine in the RSI context. The latest arguments in that controversy are discussed in the Pro-Con debate published in the present issue of the European Journal of Anaesthesiology.13,14. This could be the last chapter of a never ending story, at least for a while!
Acknowledgements Assistance with the invited commentary: none declared. Financial support and sponsorship: none declared. Conflicts of interest: TFB has received payments for lectures from Merck. Comment from the Editor: this invited commentary was checked and accepted by the editors but was not sent for external peer review.
References 1 2
3
4
5
6 7
8
9
10
11
12
13 14
Sinclair RCF, Luxton MC. Rapid sequence induction. Cont Educ Anaesth Crit Care Pain 2005; 5:45–48. Engbaek J, Viby-Mogensen J. Can rocuronium replace succinylcholine in a rapid-sequence induction of anaesthesia? Acta Anaesthesiol Scand 1999; 43:1–3. Fuchs-Buder T, Tassonyi E. Intubating conditions and time course of rocuronium-induced neuromuscular block in children. Br J Anaesth 1996; 77:335–338. Kirkegaard-Nielsen H, Caldwell J, Berry P. Rapid tracheal intubation with rocuronium: a probability approach to determining dose. Anesthesiology 1999; 91:31–36. Perry JJ, Lee JS, Sillberg VA, Wells GA. Rocuronium versus succinylcholine for rapid sequence induction intubation. Cochrane Database Syst Rev 2008;CD002788. Morris J, Cook TM. Rapid sequence induction: a national survey of practice. Anaesthesia 2001; 56:1090–1096. Fink H, Geldner G, Fuchs-Buder T, et al. Muscle relaxants in Germany 2005. A comparison of application customs in hospitals and private practices. Anaesthesist 2006; 55:668–678. Rohsbach CB, Wirth SO, Lenz K, Priebe HJ. Survey of the current management of rapid sequence induction (RSI) in Germany. Minerva Anestesiologica 2013; [Epub ahead of print]. Blobner M, Eriksson LI, Scholz J, et al. Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial. Eur J Anaesthesiol 2010; 27:874–881. Pu¨hringer FK, Rex C, Sielenka¨mper AW, et al. Reversal of profound, highdose rocuronium-induced neuromuscular blockade by sugammadex at two different time points. An international, multicenter, randomized, dosefinding, safety assessor-blinded, phase II trial. Anesthesiology 2008; 109:188–197. Sorensen MK, Bretlau C, Ga¨tke MR, et al. Rapid sequence induction and intubation with rocuronium-sugammadex compared with succinylcholine: a randomised trial. Br J Anaesth 2012; 108:682–689. Bisschops MMA, Holleman C, Huitink JM. Can sugammadex save a patient in a simulated ‘cannot intubate, cannot ventilate’ situation? Anaesthesia 2010; 65:936–941. Girard T. Pro: rocuronium should replace succinylcholine for rapid sequence induction. Eur J Anaesthesiol 2013; 30:585–589. Schreiber J-U. Con: succinylcholine should not be replaced by rocuronium for rapid sequence induction. Eur J Anaesthesiol 2013; 30:590–593.
Eur J Anaesthesiol 2013; 30:583–584 Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
