What are we discussing today?
If you’re a regular subscriber to HEFT EMCAST you will be aware of our recent discussion regarding ED rapid sequence induction. For those you who haven’t listened to the podcast, or simply need a reminder, rapid sequence induction (RSI) is the preferred method of emergency tracheal intubation outside the operating room because it results in a rapid state of unconsciousness (induction) and neuromuscular blockade (paralysis). There’s loads more information about ED RSI on the earlier episode, which you can view here along with the accompanying blog.
In today’s episode we will be looking at neuromuscular blockade for the purposes of RSI in the emergency department. Specifically, we are going to look at the two neuromuscular blocking agents (NMBA) suxamethonium and rocuronium.
We’ve covered a number of papers including a systematic review so there’s lots of information to digest. This reflects the paucity of data specific to the ED. There are some useful take home messages that are summarised at the end.
Why is this an important topic?
The choice of NMBA has become an important and controversial topic. Historically, suxamethonium was the only available NMBA and consequently has established itself as the traditional and first line agent when performing RSI. Its reported major benefits over other agents are primarily:
- Quick onset: <60 seconds
- Quick offset: due to a T1/2 of 5-8 minutes
However, suxamethonium has a number of contraindications, is associated with myalgias, and post-paralysis pain due to its depolarising properties. Consequently, non-depolarising agents such as rocuronium have increased in popularity with a number of proponents arguing in favour of their use over suxamethononium:
- Quick offset is not desirable in ED where failure to intubate in a critically unwell patient is not an option and will mandate progression along the difficult airway algorhythm
- Fewer contraindications including hyperkalaemia and family history of malignant hyperthermia
- Reduced incidence of oxygen desaturation with rocuronium
What are neuromuscular blocking agents?
A sound knowledge of basic physiology and pharmacology is required to understand how neuromuscular blockers work. The importance of this is underlined when identifying contraindications to NMBA use as well managing the various potential adverse effects associated with any individual agent.
Neuromuscular blocking agents act at the neuromuscular junction (NMJ), where acetylcholine (Ach) is released by the pre-synaptic neuron in response to motor nerve depolarisation. This causes an influx of calcium resulting in pre-synaptic release of acetylcholine into the synapse with subsequent binding at nicotinic Ach receptors on the motor end plate. This causes an influx of sodium (and some potassium) and hence depolarisation. When depolarisation is sufficiently large an action potential is generated and the muscle contracts. Acetylcholine is then broken down by acetylcholinesterase.
A simple way to remember the mechanism of action of all NMBAs is that they interfere with transmission at the NMJ and therefore decrease skeletal muscle tone.
There are two groups of NMBA:
- Non-depolarising: e.g. rocuronium, vecuronium, atracurium (MOA: competitive inhibition of Ach at nicotinic Ach receptors. Paralysis is gradual)
- Depolarising: e.g. suxamethonium (MOA: mimics the action of Ach, causing fasciculation of skeletal muscle, without breakdown by acetylcholinesterase)
So which NMBA should we use in ED?
Much of the data comparing different NMBAs in RSI comes from the anaesthetics literature. Data obtained from this specialty may not be valid or generalisable to the critically ill patient in the ED.
Circumstances that make RSI difficult are common in the ED:
- Spinal/neck immobilisation
- Unfasted patients
- Critically unwell with high oxygen demands
- Unreliable or absent past medical and drug histories
In such circumstances the correct choice of NMBA is critical to achieve optimal intubating conditions and differences between agents are likely to be magnified.
A major argument against rocuronium use in ED RDI, particularly at higher doses (1.2mg/kg), is its prolonged duration of action (>30 minutes) and the need for on-going ventilator support.
What does the literature say?
The first paper we are looking at was published in The Journal of Emergency Medicine in 2008 by William Mallon et al. It is a critical appraisal of four papers identified after searching pubmed.
- Rocuronium versus succinylcholine for rapid sequence induction of anaesthesia and endotracheal intubation: a prospective, randomised trial in emergent cases. Anesthesia and Analgesia, 2005.
- Design: non-blinded, RCT of 234 adult patients undergoing emergent surgery under GA
- Intervention: rocuronium for paralysis at 0.6mg/kg
- Control: succinylcholine for paralysis at 1.0mg/kg
- Primary outcome: intubating conditions as assessed by the intubating anaesthetist using numerical (nine-point scale) and qualitative scales
- Secondary outcome: time to intubation
- Exclusions (n=54): hyperkalaemia, neurologic disorder, burns, family history of malignant hyperthermia, difficult airway (known or anticipated)
Intubating conditions (numerical score) significantly better after administration of succinylcholine (8.6 +/- 1.1) than with rocuronium (8.0 +/- 1.5, p=<0.001)
Time to intubation: succinylcholine significantly (p=<0.0001) shorter (median, 95s) compared with rocuronium (median, 130s)
- Comparison of rocuronium and suxamethonium (succinylcholine) for use during rapid sequence induction of anaesthesia. Anaesthesia, 1998.
- Design: double-blind, RCT of 348 adult patients scheduled for elective or emergency surgery requiring ET intubation.
- Intervention: rocuronium for paralysis at two doses (0.6 and 1.0mg/kg)
- Control: succinylcholine at 1.0mg/kg
- Primary outcome: To compare the intubating conditions with the two doses of rocuronium using a three-point scale (excellent, good, poor) as assessed by a blinded observer 50s after injection of the NMBA
- Secondary outcome: comparison of the better of the two doses of rocuronium with suxamethonium at a dose of 1.0mg/kg
- Exclusions (n=34): elevated BMI, pregnancy, concomitant medications known to interact with NMBA, difficult airway (known or anticipated)
Rocuronium dose comparison: significantly higher frequency of good and excellent conditions in the higher dose (1.0mg/kg) group (p= <0.01)
Suxamethonium versus high dose rocuronium: Excellent grade intubating conditions significantly (p=0.02) higher in the suxamethonium group (80%) compared with the high dose rocuronium group (65%). The frequency of clinically acceptable intubating conditions (excellent and good) was similar between rocuronium (96.2%) and suxamethonium (96.9%, p=0.82)
- A comparison of succinylcholine and rocuronium for rapid sequence intubation of emergency department patients. Academic Emergency Medicine, 2009.
- Design: Prospective cohort study of 520 patients of all ages undergoing RSI in the ED
- Intervention: rocuronium for paralysis (average dose 1.0mg/kg) to all patients with contraindications to succinylcholine and those unable to give a history
- Control: Succinylcholine for paralysis (average dose 1.7mg/kg)
- Primary outcome: Assessment by means of a 10-point numerical descriptor for:
i) The patient’s body movements during intubation
ii) Vocal cord movement during intubation
iii) The physician’s overall satisfaction with the extent of paralysis
- Secondary outcomes:
i) Time from drug administration to paralysis
ii) Need for BVM
iii) Pulse oximetry readings during intubation
iv) Any complications
v) Serum [K+] at time of intubation
- Exclusions: none
Succinylcholine had a significantly faster onset time (39s, 95%CI 37-41s) than rocuronium (44s, 95%CI 39-50s), p=<0.04.
Succinylcholine resulted in significantly less (mean 9.1 +/- 1.1) movement than rocuronium (mean 9.1 +/- 1.5), p=0.01
There was no significant difference in vocal cord movement between succinylcholine (mean 9.2 +/- 1.6) and rocuronium (mean 9 +/- 1.6), p=0.15
Overall satisfaction was significantly higher with succinylcholine (mean 9.4 +/- 1.3) thank with rocuronium (8.8 +/- 2.0), p=<0.01
- Rocuronium versus succinylcholine for rapid sequence induction intubation. Cochrane Database of Systematic Reviews, 2008
- Design: Systematic review of all patients of any age who underwent intubation by RSI either electively or emergently
- Intervention: Search for RCTs or CTs relating to trials comparing succinylcholine and rocuronium for RSI intubation
- Primary outcome: achievement of excellent intubating conditions using a three point scale (excellent, good, poor) during RSI comparing rocuronium and succinylcholine
- Secondary outcomes: achievement of clinically acceptable (excellent or good) intubating conditions during RSI comparing rocuronium and succinylcholine
- Exclusion criteria: 21 articles excluded
37 studies included for analysis. Succinylcholine was superior to rocuronium, with relative risk 0.86 (95%CI 0.80-0.92, n=2690).
No statistical difference in intubating conditions when succinylcholine was compared to the 1.2mg/kg rocuronium however, succinylcholine was clinically superior due to its shorter duration of action.
The second paper we are going to look at is from the journal of Critical Care, published in 2015 by Richard Lyon et al and a full open access version can be found via this link.
The paper is titled ‘significant modification of traditional rapid sequence induction improves safety and effectiveness of pre-hospital trauma anaesthesia’. The study took place in the context of pre-hospital RSI performed by dedicated helicopter emergency medical service (HEMS) teams. These teams serve a population of 4.5 million in South East of England and undertake around 1500 missions per year.
This was a comparative cohort study performed to compare the efficacy of two different RSI protocols over two separate 14-month periods three years apart:
- Group 1, July 2007-October 2008: pre-hospital RSI using a protocol consisting of etomidate (0.3 mg/kg intravenously (IV)) and suxamethonium (1.5 mg/kg IV) followed by tracheal intubation
- Group 2, February 2012-March 2013: pre-hospital RSI using a modified protocol consisting of fentanyl (3 mcg/kg), ketamine(2 mg/kg) and rocuronium (1 mg/kg) followed by tracheal intubation (3:2:1 regimen). A reduced dose of fentanyl (1 mcg/kg IV) and ketamine (1 mg/kg IV) was administered in patients with haemodynamic compromise (1:1:1 regimen)
The patient population included all consecutive trauma patients undergoing pre-hospital RSI during the defined study periods. All non-trauma patients were excluded. The decision to intubate was made by the attending on-scene risk-benefit assessment. Monitoring includedoxygen saturation, heart rate (HR), electrocardiogram and capnography.
The primary outcome measure was intubation success, and the acute haemodynamic response (hypertension, hypotension, tachycardia) to laryngoscopy and tracheal intubation.
So what did they find?
After exclusions (n=13) 261 patients were included for analysis (Group 1, n=116; group 2, n=145). The key results were:
- Baseline characteristics: Group 2 were significantly older (39 years versus 45 year, p=0.03) and had significantly higher injury severity score (22 versus 26, p=0.019)
- Intubating conditions: Laryngoscopy of patients in group 2 resulted in significantly better laryngeal views (p=0.013). Tracheal intubation was 100% successful within three attempts for both groups, however, first attempt intubation success was significantly higher in group 2 compared to group 1 (95% versus 100%, P = 0.007)
- Haemodynamic response to laryngoscopy and tracheal intubation: Seventy-seven patients (66%) in group 1 and 111 patients (77%) in group 2 were administered a full-dose RSI protocol. Baseline haemodynamic measures were similar in the two groups. For each group, the haemodynamic response following a reduced-dose RSI was similar to the response observed following a full-dose RSI
o A hypertensive response to laryngoscopy and tracheal intubation was less frequent following Group 2 RSI (79% versus 37%; p < 0.0001)
o A hypotensive response was uncommon in both groups (1% versus 6%; p = 0.05)
- Outcome to hospital discharge: no significant mortality difference between the two groups; on subgroup analysis for head injury severity no significant difference was found
o On univariate analysis the only factors significantly associated with mortality were age, initial Glagow coma score (GCS), injury severity score (ISS), and RSI dose
o After adjusting for these variables, only age, initial GCS, and ISS remained independently associated with mortality
So what’s the take home message?
The findings of this study suggest that for pre-hospital RSI in trauma patients a combination of fentanyl, ketamine and rocuronium produced superior intubating conditions and a more favourable haemodynamic response to laryngoscopy and tracheal intubation.
Ketamine did not appear to have any adverse effects on head injury outcomes (although sample size on subgroup analysis was small).
- The study compared the above RSI regimen with etomidate and suxamethonium, which is not the standard operating procedure in most UK A&Es
- The study took place in the pre-hospital environment and not the ED
- Retrospective cohort study
- Group 1 patients had higher injury severity scores and were older
The next article takes a look at whether suxamethonium use in RSI is associated with great oxygen consumption than rocuonium. The paper was published by S. Taha in the journal Anaesthesia in 2010.
Why did we include this paper?
Because suxamethonium is a depolarising NMBA that causes skeletal muscle fasciculation it has been postulated that this hastens desaturation after pre-oxygenation during RSI. This is a big issue for all patients undergoing general anaesthesia however, in the undifferentiated patient presenting to ED with critical illness (and therefore high oxygen demands) its manifestation could have profound effects.
A prospective partially blinded RCT of 60 ASA I or II patients admitted for elective surgery in a single centre. The country and location of the study is not described.
The primary outcome was to assess the time taken to desaturate to 95% folowing RSI. Patients were randomly assigned to one of three RSI protocols:
- Group R: lidocaine, 1.5mg/kg; fentanyl, 2mcg/kg; propofol, 2mg/kg; rocuronium, 1mg/kg
- Group S: lidocaine, 1.5mg/kg; fentanyl, 2mcg/kg; propofol, 2mg/kg; suxamethonium, 1.5mg/kg
- Group SO: saline, saline, fentanyl, 2mcg/kg; propofol, 2mg/kg; suxamethonium, 1.5mg/kg
Time of apnoea was measured from removal of the facemask after pre-oxygenation to when the patients desaturated to 95%; the tracheal tube was then attached to the ventilator.
Secondary outcomes included:
- Intensity of visible muscle fasciculations: Four point score
- Duration of muscle fasciculations
- End expiratory oxygen and carbon dioxide after initiation of ventilation
The anaesthetist performing pre-oxygenation also scored the fasciculation score, duration of fasciculation, and duration of apnoea. They were blinded to the treatment arms.
What did they find?
Patient characteristics were similar for each of the three groups.
Median (IQR) time to 95% desaturation was significantly shorter in group S and SO compared to group R:
- Group S vS Group R: 358s vs 378s (p=0.003)
- Group SO vS Group S: 242s vs 378s (p=0.001)
- Group SO vS Group R: 242s vs 358s (p=0.001)
The fasciculation score and duration of fasciculation were significantly greater in Group SO than in Group R and Group S, and greater in Group S than in Group R. Full data is available in the article.
What’s the take home message?
When suxamethonium is adminstered for RSI of GA, a faster onset of oxygen desaturation is observed during the subsequent apnoea compared with rocuronium. Co-adminstration of lidocaine and fentanyl with suxamethonium prolongs the time to desaturation.
The final article we are going to discuss today was published in 2011 and is from the journal ACTA Anaesthesiologica Scandinavica titled ‘Desaturation following rapid sequence induction using succinylcholine vs. rocuronium in overweight patients.
Why did we include this paper?
To look at whether hypoxaemia is more common in RSI involving suxamethonium versus rocuronium. The reasons are exactly the same as the above paper except the patient population is slightly different.
This was a prospective double-blind RCT between August 2007 to February 2009. Sixty patients with BMI 25-30 kg/m2 were prospectively recruited; all patients were ASA grade I and II, aged 23-64 years, and undergoing elective surgery requiring general anaesthesia.
Exclusions included: contraindications to either suxamethonium or rocuronium, haemoglobin < 6.8mmol/l, pregnancy, significant cardiovascular disease, and known/anticipated difficult airway.
The time from administration of a NMBA to an oxygen saturation (SpO2) of 92% was defined as the ‘safe apnoea time’. The time taken from initiation of ventilation (when SpO2 reached 92%) to SpO2 reached 97% was defined as the ‘recovery period’.
The primary outcome measure was the ‘safe apnoea time’ and a 30 second difference was considered clinically relevant.
Patients were randomised to receive either 1.5mg/kg of suxamethonium or 0.9mg/kg of rocuronium. The RSI regimen comprised NMBA, propofol (to achieve a target serum concentration 5 micrograms/ml), midazolam (0.02mg/kg), fentanyl (1.5micrograms/kg).
Patients were intubated 60 seconds after administration of a NMBA. Following confirmation of tube placement the tracheal tube was left open to air until oxygen saturation fell to 92%. The patient was then connected to the ventilator.
A series of arterial blood gas (ABG) samples were taken to measure oxygen saturation at various points during the RSI:
- ABG 1: At baseline, prior to pre-oxygenation
- ABG 2: After 3-minutes pre-oxygenation
- ABG 3: Once SpO2 fell to 92%
Times were recorded when oxygen saturation (SpO2) reached 98%, 96%, 94%, and 92%.
So what did they find?
Mean safe apnoea time was significantly less with the succinylcholine group (283 seconds, 95%CI 257–309 seconds) compared with the rocuronium group (329 seconds, 95%CI 303–356 seconds; p=0.01).
The mean recovery period was significantly longer in the succinylcholine group (43 seconds, 95%CI 39-48 seconds) compared with the rocuronium group (36 seconds, 95%CI 33-38; p=0.002)
What have we covered?
- Neuromuscular blocking agents are used in RSI and result in paralysis of skeletal muscle
- The use of rocuronium in RSI is increasing. From the ED perspective, this may be advantageous:
- Quick offset is not desirable in ED
- Fewer contraindications including hyperkalaemia
- Reduced incidence of oxygen desaturation with rocuronium
- From the papers we have looked at:
Suxamethonium was favourable to rocuronium in most instances however, data is largely from the anaesthetics literature
A higher dose of rocuronium (1.2mg/kg) may produce comparable intubating conditions compared to suxamethonium at standard dose (1.0mg/kg)
In the pre-hospital environment, a modified RSI protocol utilising rocuronium resulted in favourable intubating conditions and haemodynamic response to laryngoscopy and tracheal intubation
Rocuronium may, in overweight patients, increase the safe apnoea time compared to suxamethonium however, the best study looking into this is not of high enough quality to inform practice.
Take home messages
Use of a modified RSI protocol utilising rocuronium instead of suxamethonium may be advantageous in a specific group of patients in certain environments. Whether this translates into an advantage in the ED is debatable.
Those undertaking RSI in the UK should be proficient in the skill, which includes rescue techniques, before considering its application.
- Swaminathan A. 2014. Roc Rocks and Sux Sucks! Why Rocuronium is the Agent of Choice for RSI. emDOCS. http://www.emdocs.net/roc-rocks-sux-sucks-rocuronium-agent-choice-rsi/. Accessed 11th July 2015.
- Mohammad EO, Connolly LA. 2010. Rapid Sequence Induction and Intubation: Current Controversy. Anesth Analg. 2010 May 1;110(5):1318-25
- Mallon W, Keim S, Shoenberger J, et al. 2008. Rocuronium vs. succinylcholine in the emergency department: a critical appraisal. J Emerg Med. 37(2):183-8
- McCourt KC, Salmela L, Mirakhur RK, et al. 1998. Comparison of rocuronium and suxamethonium for use during rapid sequence induction of anaesthesia. Anaesthesia. 1998 Sep;53(9):867-71
- Lyon R, Perkins Z, Chatterjee D, et al. 2015. Significant modification of traditional rapid sequence induction improves safety and effectiveness of pre-hospital trauma anaesthesia. Critical Care. 015, 19:134
- Taha S, El-Khatib MF, Baraka AS, et al. Effect of suxamethonium vs rocuronium on onset of oxygen desaturation during apnoea following rapid sequence induction. Anaesthesia, 2010, 65:358-361
- Tang L, Li S, Huang S, et al. Desaturation following rapid sequence induction using succinylcholine vs. rocuronium in overweight patients. Acta Anaesthesiol Scand 2011; 55: 203–208