Roc Rocks, I’ll miss you Sux

Rocuronium vs Suxamethonium(Succinylcholine)

I remember teaching the Advanced Airway Workshop and having one slide with “SUX is KING”. Times have changed!
Which is the better paralytic agent to use in the Emergency Department; Suxamethonium(Succinylcholine for our US colleagues) or Rocuronium? This argument has been ongoing for some time, with debates, podcasts and written reviews by proponents each taking strong positions, sometimes quite belligerently. Here is the evidence. I have highlighted the important points to save you reading time.

There are a list of what I call light concerns, ‘fluff’ if you like, that distract from real concerns and then there is the evidence based material, that makes a difference. Let’s get rid of the fluff first.

One of the first arguments against Suxamethonium, is its fasciculation-induced muscle aches and pains that the patient may experience when woken, in ICU. They are real and we should certainly care that the patient may have discomfort down the track. However I have a single goal; to establish/protect the airway. No-one will thank you if you can’t get this right. So lets not spend too much time on the aches and pains. Rhabdomyolysis is a different matter, which will be discussed later. A further concern relates to what we do, if we can’t intubate and have used a long- lasting paralytic agent, such as Rocuronium? The approach of letting the patient wake up, has no place in the emergency department. This statement belongs to anaesthetics and elective procedures, where they can wake them up and play another day. In the emergency department, the reason we needed to intubate in the first place is still there.

With the introduction of  ‘Sugammadex’, a rapid reversal agent for Rocuronium, this should no longer be of concern.
Proponents in favour of suxamethonium use the head injured patient with an intracranial bleed as an example. Their main argument is that the Neurosurgeon may need to examine them, so it is appropriate to wake them up.
Neurosurgeons care about what the patient was doing when they came in, their co-morbidities and the single most important thing, the CT brain.  The examinations are usually very basic and involve movement of the limbs, pupil size and reactivity and test for doll’s eyes, or the oculocephalic reflex.  This examination should be done prior to intubation, but sometimes this isn’t possible.
In the rare occasion where this can be done, Suxamethonium will wear off and Rocuronium can be completely reversed.

What are the things that matter? What are those things important to establishing an airway? Here is my list.

1. How quickly will I induce paralysis to allow intubation and how good will my intubation conditions be?
2. Will any of these drugs reduce my available apnoeic time? This means, will my patient desaturate faster on one drug rather than the other and will this matter in the real world?
3. Will any of these drugs have adverse reactions?

ADVERSE REACTIONS: SUX vs ROC

Are there adverse reactions related to these two drugs? Could these adverse reactions change my practice?
ROCURONIUM: There are NO adverse reactions.

SUXAMETHONIUM: There is a huge list. In the acute presentation to the emergency department, we can’t always get a history from the patient, nor a detailed collateral history. Certainly we need to think of potential complications but sometimes, this is difficult to do.
One of the main areas of concern with Suxamethonium is its use in patients where there is a chance of hyperkalaemia occurring. The list below, although not extensive, is of those cases where presentations may be hyperkalaemia related:

• Existing hyperkalaemia
  • There are multiple examples that we have anecdotally discussed of the patient developing a sinusoidal waveform on the monitor and then arresting, following Suxamethonium, because the potassium rose to 9mmol/L.
  • Rhabdomyolysis – a subclinical presentation of malignant hyperthermia can occur(1)
  • Muscular dystrophies
  • Myopathies
  • Denervating injuries > 72 hours i.e. Stroke, spinal injury
  • Burns > 72 hours (peaks 7-10 days)
  • Crush injuries > 72 hours (peaks 7-10 days)
  • Severe infections > 72 hours
  • Patients found down for unknown time

The drug is also associated with

• Hypotension/hypertension
• Bradycardia
• Masseter spasm.
• Increased pressures in the brain, eye and stomach.
• Myalgias secondary to fasciculations

Malignant hyperthermia, a potentially fatal condition, has been estimated to occur in 1:100,000(2) cases. Subclinical presentations can also occur leading to hyperkalaemia(1).
The reality is that these adverse events aren’t common; they are rare, however Suxamethonium is responsible for about 80% of them(3).  The calculated rate of occurrence is 1:1000 – 1:25000 with a 6% mortality. With these figures it means that all of us will encounter a problem with Suxamethonium.
With this adverse effect profile why would we use Suxamethonium, unless it is so vastly superior to anything else?

TIME TO PARALYSIS
The other questions that we need to answer, relate to how quickly do the drugs give us paralysis allowing intubation and the quality of those intubating conditions?

Before we have this discussion, its important to point out that most of the studies done, were carried out in operating theatres by anaesthetists on patients with ASA I and II classifications. In some studies, induction was commenced several minutes before paralysis. So these were essentially healthy patients having elective procedures and the process of induction followed immediately by paralysis did not occur, as it does in the emergency airway.

What doses do we use?

The dose of Suxamethonium is 1.5mg/kg. Doses given in studies varies between 1 and 1.5mg/kg.
The dose of Rocuronium varies in most studies. Dose of 0.6mg/kg, 1mg/kg and 1.2mg/kg have been used.

McCourt(4) found no difference between the two paralytics at 60-90 seconds with 1 mg/kg of Suxamethonium and 0.9mg/kg of Rocuronium.

Perry et al (5) found no statistically significant difference in intubating conditions between Suxamethonium and Rocuronium when 1.2mg/kg of Rocuronium was used.
Crul(6) found excellent intubating conditions at 45seconds with 0.9mg/kg of Rocuronium when propofol and alfentanyl were used.
Magonan T. et all(7) found that at doses of 0.9mg/kg -1.2mg/kg, Rocuronium is a good alternative to Suxamethonium.
Marsch et al (8) found no difference at 60 seconds between the two drugs, at lower Rocuronium doses of 0.6mg/kg.

What we need when intubating is the earliest possible paralysis so we can start. At  doses of 1.2 mg/kg of Rocuronium, it is described as having the same onset of paralysis as Suxamethonium.

Is there a difference in the ease of intubation with the two drugs?

Sparr(9) found that with 1mg/kg for both drugs that there was no difference in clinically acceptable conditions(excellent plus good) between the two drugs, as in the table below.

	ROC 1mg/kg	SUX 1mg/kg
n	130	127
Excellent	85 (65%)	101 (80%)
Good	40 (31%)	22 (17%)
Poor	5 (4%)	4 (3%)

Table 1 Intubating conditions between suxamethonium and rocuronium
The difference between excellent and good may only be a slight amount of diaphragmatic movement in response to intubation ie., something clinically imperceptible. The Goldberg scale is used to rate intubating conditions. It is a numerical system where < 3 is described as excellent and 4-6 is good. Looking at the table below, if everything else was normal and there was subclinical movement of the diaphragm, that would be classed as good. (10). In fact this is what happened.

SCORE	EASE OF INTUBATION	VOCAL CORDS	RESPONSE TO Intubation
1	Good	Open Full	None
2	Fair	Open Midway	Diaphragmatic movement
3	Difficult	Movement	Moderate Coughing
4	Fair	Closed	Severe coughing

 Table 2 Definition of Intubating Conditions

Marsch’s study (8) demonstrated the ease of laryngoscopy and the condition of the vocal cords was the same, whether Suxamethonium or Rocuronium was used, even though a dose of 0.6mg/kg of Rocuronium was used here.
Wright PM, et al(11) found that at rocuronium doses of >1mg/kg, vocal cord movement could be eliminated as with suxamethonium.

Perry (5) in the Cochran review stated:

“We found no statistical difference in intubation conditions when succinylcholine was compared to 1.2mg/kg Rocuronium…..”

Do these drugs affect the time I have for intubation?

Does apnoeic desaturation occur earlier in one drug, decreasing the amount of time to intubate before needing to intervene with a bag value mask?

Taha et al (12) looked at the time to desaturation to 95% with both paralytics and the same induction agents. The patients were intubated at 50 seconds and the endotracheal tube left open until the level of desaturation was reached.  The Rocuronium group took 20 seconds longer, for desaturation. That’s significant, however when we look at total times to desaturation in these patients, it’s less impressive, as they are very long, reflecting that this was essentially a healthy population this was conducted upon, in an elective environment. These times may be far shorter in the sicker cohorts.

GROUP	Drugs-induction	Paralysis	Time to reach 95%
R	Lignocaine 1.5mg Fentanyl 2mg/kg Propofol 2mg/kg	Rocuronium 1mg/kg	378 sec (p<0.001)
S	Lignocaine 1.5mg/kg Fentanyl 2mg/kg Propofol 2mg/	Suxamethonium 1.5mg/kg	358 sec (p<0.001)
SO	Propofol 2mg/kg	Suxamethonium 1.5mg/kg	242 sec

Table 3 Time to Desaturation(12)

The trend of Suxamethonium  leading to earlier desaturation, relates to increased oxygen use secondary to the fasciculations it causes. These results were reproduced in the overweight population.(7) In this study Tang used patients with a BMI of 25-30. The doses of drugs used was 1.5mg/kg of Suxamethonium and 0.9mg/kg or Rocuronium. They looked at the ‘safe apnoea time’, which was defined as the time from administration of the neuromuscular blocking agent to saturations dropping to 92%. The mean recovery period was also measured. This was the time for saturations to reach 97% once they had dropped. The results are shown in the table below:

	Mean Safe Apnoea times (s)	Mean recovery period
Succinylcholine	283 (257-309)	43 (39-48)
Rocuronium	329 (303-356)	36 (33-38)

Table 4 Safe Apnoea Times(13)

Rocuronium is slower to desaturation and faster to recovery in this patient group.

Marsch(5) found the intubation sequence to be shorter with Suxamethonium(81 seconds vs 95 seconds) , but no difference in the quality of intubation and no difference in the desaturations.

IN SUMMARY

In summary we see the following:

• In terms of intubating conditions, the two drugs are equal.
• In respect to onset of paralysis, they are equal.
• In terms of adverse events profile, there is no competition Rocuronium wins.
• In terms of apnoeic time available the trend is again towards Rocuronium.

The Main Argument for the use of Suxamethonium

The main argument for the use of Suxamethonium(succinylcholine) appears to be its  duration of action. Succinylcholine has a duration of action of 5-8 minutes, with a rapid turnoff. Rocuronium in smaller doses has a duration of action of about 40 minutes and with the higher 1.2mg/kg doses approximately 55 minutes.

When Perry et al(5), in their Cochran review, stated that there was no difference between the two drugs, in terms of intubating conditions, they still found in favour of suxamethonium saying “However succinylcholine was clinically inferior as it has a shorter duration of action”(5).

Those in favour of Suxamethonium state that if you cant intubate, you only need to bag valve mask the patient for a few minutes, the time it takes for suxamethonium to wear off, rather than the 40-50 minutes Rocuronium would take. Those for Rocuronium say “just reverse it” with sugammadex. It takes approximately 2 minutes to reverse. The question then is;”Now what?” The reason we needed to intubate that patient is still there.

The greatest concern expressed relates to what might happen when paralytic is given, the patient loses all tone and then you can’t oxygenation nor ventilate. that most people have is, what happens if I give paralytic and I can’t oxygenate or ventilate and can’t intubate?
The reality is, that apnoeic desaturation tends to occur very early in the process. If it occurs at 2 minutes you have no choice with Suxamethonium, you will have to wait a further 3 to 6 minutes for it to wear off. By this time you would have tried alternatives and probably progressed to a surgical airway.
If the same thing happens with Rocuronium you can reverse it. Its action is very rapid; however the time to draw up and give and then wait to have effect is 4-6 minutes, so no real benefit over suxamethonium, but no worst.
Those that support Rocuronium see the longer paralysis as being helpful. If intubation is difficult then alternative techniques can be attempted and paralysis is ongoing. With Suxamethonium further doses would need to be given.

CONCLUSION

In conclusion, on one side we have Suxamethonium a drug we have used forever in the emergency department that has served us well. It has the potential for severe adverse reaction and can result in less apnoeic time available. On the other side we have Rocuronium with no adverse reactions, giving similar onset times, the same quality of intubating conditions, and a longer duration of action, which can be rapidly reversed.

Which one would you use? 

It’s a no brainer to me….There may be a changing of the guard! Goodbye Sux, I’ll miss you.

The final word belongs to Lee(14) who offers a eulogy for Suxamethonium

References.

1. Le Puura et al. Suxamethonium-induced rhabdomyolysis in a healthy middle-aged man. Acta Anaesthesiol Belg. 2000;51(1):51-3.
2. Brady JE, Sun LS, Rosenberg H, Li G SO. Prevalence of malignant hyperthermia due to anesthesia in New York State, 2001-2005. Anesth Analg. 2009;109(4):1162.
3 Naguib, M, Magboul MM. Adverse effects of neuromuscular blockers and their antagonists. Middle East J Anaesthsiol 1998 Jun;14(5)341-73
4 K.C. McCourt et al. Comparison of Rocuronium and Suxamethonium for use during rapid sequence induction and anaesthesia.  Anaesthesia, 1998, 53, 867-871
5 Perry JJ et al. Rocuronium succinylcholine for rapid sequence induction intubation. Cochran Database Syst Rev. 2008 April 16; (2) : CD002788
6 Crul JF et al. Rocuronium with alfentanil and Propofol allows intubation within 45 seconds. European Journal of Anaesthesiology 1995; 12 (suppl.11) 111-2
7 Magonan T. et al. Comparison of Rocuronium, Succinylcholine and Rocuronium for rapid sequence induction of anaesthesia in adult patients. Anaesthesiology 1993; 79:913-918
8 Marsch SC et al. Succinylcholine versus Rocuronium for rapid sequence intubation in intensive care: a prospective randomised controlled trail. Crit Care. 2011 Aug 16: 15(4) R. 199.
9 Perry JJ, Lee J, Wells G. Are intubation conditions using Rocuronium equivalent to those using succinylcholine?. Accid Emerg Med 2002 Aug; 9(8) : 813-23.
10 Sparr et al Acta Anasthelogica Scandinavica 1996: 40:425-430 found that acceptable intubations were similar in the two groups, the rate of excellent intubations was/ en in Rocuronium.
11 Wright PM, et al. Onset and duration of Rocuronium and Succinylcholine at the adductor pollicis and laryngeal adductor muscles if anaesthetised humans Anaesthesiology. 1994; 81:1110
12 Taha sk et.al. Effect of Suxamethonium vs Rocuronium on onset of oxygen desaturation during apnoea following rapid sequence intubation. Anaesthesia 2010 April: 65 (4) 358-61
13 Tang L et al. Desaturation following rapid sequence induction using succinylcholine vs. Rocuronium in overweight patients. Acta Anaesthesiol. Scand 2011 Feb; 55 (2): 203-8
14 Lee,C. Goodbye Suxamethonium. Anaesthesia. 2009 Mar;64 Suppl 1:73-81