PHARM Podcast 89 – Does Roc rock and Sux suck?

Dr Cliff Reid reveals Rocketamine to the world at SMACC 2013

Dr Cliff Reid reveals
Rocketamine to the world at SMACC 2013

Today on the podcast,  Dr Rob Bryant, EM doctor from
Salt Lake City, Utah, is back to discuss Roc vs Sux! WHEN
DOES SUX SUCK?, AND DOES ROC. ALWAYS ROCK?

  Succinylcholine is a common neuromuscular
blocking agent used in emergency departments worldwide, and in
systems with pre-hospital RSI capabilities. Some systems (Layton,
UT, USA) have encountered resistance when they proposed the
addition of Rocuronium to their prehospital RSI programs.
Some people feel safe using Succinylcholine, due to
familiarity with the medication, and due to the assumption (based
on anesthesia algorithms) that it is safer than Rocuronium and will
wear off before profound hypoxemia ensues in the event of a failed
airway, is this true?
 
Critical hemoglobin desaturation will occur before return
to an unparalyzed state following 1 mg/kg intravenous
succinylcholine.
Anesthesiology.
1997 Oct;87(4):979-8
This is the
article where the ‘Benumof’ curves come from, detailing the
variable safe apnea durations in the healthy, young, obese, and
sick. Mean time to recovery of twitch height is 8.5 minutes. Time
to desat in obese adult and normal child is 4 min, ill adult 6.25
minutes, and normal adult 10 minutes. This debunks the
‘succinylcholine is safe because it wears off’ myth.
Hemoglobin desaturation after succinylcholine-induced
apnea: a study of the recovery of spontaneous ventilation in
healthy volunteers.
Anesthesiology.
2001 May;94(5):754-9
This evaluates
the belief that patients will start breathing sufficiently rapidly
to prevent significant oxygen desaturation. 12 healthy volunteers,
each pre-oxygenated, and given 1mg/kg succinylcholine. Saturations
were monitored, and when sats dropped below 80% chin lift and
assisted ventilations were provided. Six (50%) patients dropped
below 95%, and in four, below 80%. Mean values for apnea duration,
eye opening on command, and hand squeeze were 5.2, 5.7, and 7.7
minutes. Succinylcholine dosage and apnea-induced
hemoglobin desaturation in patients
Anesthesiology.
2005 Jan;102(1):35-40
This evaluates
whether a lower dose of succinylcholine. would produce a faster
recovery of spontaneous ventilation. 60 patients randomized to 1/kg
or 0.56/kg of succinylcholine or saline, and then apnea time to
first diaphragmatic movement was measured. All patients received
2mg/kg propofol. Desaturation <90% occurred in 85%, 65%, and
45% of patients, with a dose response effect observed in those
receiving succinylcholine. Time to diaphragmatic movement was not
effected, (4.7, 4.8, and 2.7 minutes respectively.) Dose adjustment
to a lower dose of succinylcholine. is not appropriate in the
ED/EMS population due to the high frequency of hemodynamically
compromised patients that will require a  higher dose of
succinylcholine (1.5-2mg/kg) to achieve rapid neuromuscular
blockade.   Succinylcholine is
short acting, and in the setting of a difficult airway it may need
to be redosed to provide optimum intubating conditions, what are
the
issues with re-dosing
succinylcholine?
  There are
theoretical issues that the duration of action from a second dose
of Succinycholine will be significantly longer than anticipated.
Our EMS / ED / ICU patients that need airway protection still need
it in a CICV setting, ‘cancelling the case’ is not an option.
Arguing for a medication that will wear off in the event of failure
does not resolve the physiological insult to the patient that needs
airway protection / ventilatory assistance. Some people
are resistant to changing a medication that they have used for a
decade, what are the problems with succinylcholine?

  Succinylcholine has some rare but
potentially life-threatening problems that include hyperkalemia,
malignant hyperthermia, bradycardia, masseter spasm and
questionable increased intracranial pressure. Some profoundly
hyperkalemic patients are not obviously identifiable prior to lab
evaluation. The US drug industry has been
plagued in recent years by production shortages of various
medications, including Succinylcholine, etomidate, and sodium
bicarb. Rocuronium. proponents argue that Rocuronium. is
safer, and contributes to a prolongation of the safe apnea
duration, explain:
 
Effect of suxamethonium vs Rocuronium on onset of oxygen
desaturation during apnoea following rapid sequence
induction
Anaesthesia.
2010 Apr;65(4):358-61
Three arm trial (n=20 per group)
comparing Rocuronium, or Succinylcholine with fentanyl and
lidocaine pre-med., versus Succinylcholine with propofol. Mean time
to desat <95% was 358 sec. in the Succinylcholine, Fentanyl
and lidocaine group, 378sec in the Rocuronium Fentanyl and
lidocaine group, and only 248 sec. in the Succinylcholine and
propofol group. Giving a Lido / fentanyl premed could decrease the
difference in safe apnea durations between Rocuronium and
Succinylcholine, however this adds to medication administration
times, and does not avoid the inherent potassium issues related to
succinylcholine use. Rocuronium proponents may argue
that Suggamadex can rapidly reverse NMB from Rocuronium and provide
a layer of safety.
  Can
sugammadex save a patient in a simulated ‘cannot intubate, cannot
ventilate’ situation?
Anaesthesia.
2010 Sep;65(9):936-41
This was a manikin based ‘cannot
intubate, cannot ventilate’ scenario where the total time taken for
anesthetic teams to prepare and administer suggamadex was studied.
The mean time to administration of sugammadex was 6.7 min,
following which a further 2.2 min (8.9 min total) should be allowed
to achieve a train of four ratio of 0.9. Multiple dosing errors
occurred. This highlights that suggamadex might not have saved this
patient in a CICV situation. Rocuronium may delay
appropriate post intubation analgesia, what is the solution to
this?
  Effect
of paralytic type on time to post-intubation sedative use in the
emergency department.
Emerg
Med J. 2013 Nov;30(11):893-5.
  Retrospective case review of 200
intubations. 77% of patients were started on a propofol or
midazolam infusion, the remainder received bolus dosing of sedative
agents. Mean time to sedative administration was 27 vs 15 min for
Rocuronium vs Succinylcholine. Long-acting neuromuscular
blocker use during prehospital transport of trauma patients.
Air
Med J. 2013 Jul-Aug;32(4):203-7.

  51 trauma patients intubated in the
prehospital setting. 42% of these patients received a long acting
neuromuscular blocker. Time to sedative use following intubation
was recorded. The LA-NMB group received sedatives less promptly
after intubation compared with those who did not receive LA-NMBs
(16 vs. 7 minutes, respectively; P = .04). Poor post intubation
sedation and analgesia can easily be avoided by the use of fentanyl
with induction agent  / neuromuscular blockade dosing, and a
post intubation checklist that includes identification of
appropriate analgesia and sedation administration. What
situations is succinylcholine still better than
Rocuronium?
  In situations where
a rapid and timely neurological evaluation might change management,
the shorter duration of succinylcholine is preferred. Examples
include patients intubated for seizure control, patients with
traumatic intracerebral bleeds, stroke patients, and patients who
have been intubated following a cardiac arrest that need a neuro
assessment to determine eligibility for Targeted Temperature
Management.  EEG monitoring is essential for any intubated
seizure patient, and non-convulsive status is well described. Most
surgical intervention decisions for traumatic intracerebral
bleeding are based on available imaging studies, and not the
clinical exam. Patients with strokes who need intubation are likely
to have higher NIHSS scores, and may be more likely to have poor
outcomes from TPA administration. Securing a safe airway without
desaturation or inducing hyperkalemic complications trump these
arguments. For short (30 min) transport times, it is conceivable
that the duration of neuromuscular blockade from Rocuronium alone,
compared to succinylcholine and then vecuronium would produce a
more favorable duration of paralysis with a patient emerging from
their neuromuscular blockade at the time of hospital arrival.
Have there been any prehospital studies, or emergency
department based studies comparing intubation success with
Rocuronium vs Succinylcholine?
 
Rocuronium
versus succinylcholine in air medical rapid-sequence
intubation.
Prehospital
emergency care 2011;15:457-463 1045 intubations,
46% received Succinylcholine. There was an overall 59% First pass
success rate, 31% required 2 attempts and 7% required 3 or more
attempts. After propensity score adjustment, Succinylcholine was
associated with a higher incidence of first pass success (odds
ratio 1.4 (1.1-1.8). First attempt success with Rocuronium was 55%
(50-59%) and 64% (59-68%) for succinylcholine. One possible
explanation for the decreased first pass success could be the
potential impatience of the intubator to wait for optimum
intubating conditions before the first attempt.  This could
occur if the Rocuronium was taking longer to achieve neuromuscular
blockade than the succinylcholine. The first pass success rates
seem low in this study compared to a rate of 76% in a 2012 HEMS
study. Prehosp Emerg
Care. 2012 Apr-Jun;16(2):293-8

Summary. Rocuronium can produce optimum
intubating conditions in a similar timeframe to succinylcholine and
has no significant contra-indications. Succinylcholine is not safer
than Rocuronium as its duration of action is likely to exceed the
safe apnea duration of most EMS / ED patients. Rocuronium has
beneficial effects on the safe apnea duration in our sick EMS and
ED patients, and has the added benefit of avoiding long acting neuromuscular
blockade during transport(i.e RSI dose should be sufficient for intubation and transport period to ED) The use of Rocuronium with Ketamine provides an
additional mathematical benefit of similar weight-based dosing,
decreasing the cognitive load of multiple medication calculations
during the preparation phase of RSI.  
Final word: Anaesthesia, 2009, 64
(suppl. 1) 73-81,
Goodbye
Suxamethonium!
A review
intended to offer a eulogy for suxamethonium . Additional
References:
Is
Rocuronium as effective as succinylcholine at facilitating
laryngoscopy during rapid sequence
intubation?
Best
Bets Literature review. http://www.bestbets.org&nbsp;
SHOW
NOTES:

  1. Roc
    rocks, sux sucks, pharm shownotes
  2. LITFL
    article 

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7 Comments
  1. I am also a Pre- (Careflight Medical Services w some RFDS postings) & In-hospital covert to Roc and RocKet but held out on Roc for longer than others due to my concern about an anaphylaxis to Roc. The other benefits now outweigh this low risk concern but it does beg the question of why we don’t carry Sugamadex in the pre-hospital environment to treat this rare but nasty side-effect. I have no desire to use Sugamadex for any other reason so do you think this is enough of a justification to carry it or would our usual anaphylaxis management be sufficient?

    • Thanks for question Euan. I know of only one prehospital service in Australia that used to carry Sugammadex, the Brisbane rapid response trauma car. They never used it and now have removed it from their packs.

      Sux can give anaphylaxis as well, but yes roc seems to have a higher incidence, yet I am yet to see it myself. If in unlucky event it was to occur then yes I would give epinephrine, hopefully the airway is already secure!

      I imagine when Sugammadex becomes generic and is cheap then we will have it in our packs

      • I guess the question is whether suggamadex REALLY reverses roc-induced anaphylaxis I recall a paper, perhaps two years ago, BJA IIRC, where report of roc-induced anaphylaxis Rx with suggamadex successfully

        BUT

        note also that roc is placed as intermediate risk of anaphylaxis compared to sux : “Data from intradermal testing suggested that rocuronium is intermediate in its propensity to cause allergy in known relaxant reactors compared with low-risk agents (e.g. pancuronium, vecuronium) and higher-risk agents (e.g. alcuronium, succinylcholine).” British Journal of Anaesthesia 86 (5): 678-82 (2001) Rocuronium: high risk for anaphylaxis

        Of course, one of the problems is that when the %$&* hits the fan, you may well have given other agents as well as roc at the time you say “I think this is Roc anaphylaxis”

        ie you won’t actually know what has caused the reaction, as you will most likely have given several other drugs at the same time, including quite possibly antibiotics. But now degranulation has occurred, and what you are dealing with is SIMPLY ANAPHYLAXIS, cause unknown. The specific diagnosis comes later with the lab results…

        Now the irritating question – have there been any cases of anaphylaxis to suggamadex? I think there was a case report…

        Regardless, if you are DOUBLY unlucky to need prehosp RSI and then have anaphylaxis to roc, I am pretty sure that bucketloads of adrenaline (where’s the epinephric gland?) would be a reasonable option, rather than carting around suggamadex.

  2. Interesting articles from Western Australia published in BMJ in 2013 looking at incidence of muscle relaxant associated anaphylaxis between 2002 and 2011 (http://www.ncbi.nlm.nih.gov/pubmed/23335568). Rocuronium was implicated in 56% of cases, Vecuronium in 11% and Suxamethonium in 11%. Risk of anaphylaxis to Rocuronium was calculated as 8:100,000 exposures compared to 2.8:100,000 for Vecuronium. Apparently risk could not be calculated for Suxamethonium. Recent discussions on an Anaesthetic blog site report incidences as being much higher, and broadly comparable between Sux and Roc (http://gasexchange.com/questions/sux-anaphylaxis-vs-roc-anaphylaxis-and-rsi/)

    As KIdocs alludes to above Rocuronium is regarded as an intermediate risk drug but Suxamethonium as high risk. Very little comfort if you are faced with a patient having a reaction on the end of the needle I know. There are case reports of Roc-mediated anaphylaxis reversal (http://bja.oxfordjournals.org/content/109/4/646.full) but high doses are required to mop up any residual Roc as presumably if any is left it just continue to feed the reaction. Whilst “removal of the allergen” is an integral part of anaphylaxis treatment where possible I’m not sure if that on its own can justify carrying another drug in the unlikely event of a Roc reaction – which could well have been to anything else you have given (anaphylaxis has been reported following an injection of sterile water apparently).

    Minh do you have any data on how often reactions occur in prehospital practice?

  3. Sorry first part should read:

    “Interesting articles from Western Australia published in BJA in 2013 looking at incidence of muscle relaxant associated anaphylaxis between 2002 and 2011 (http://www.ncbi.nlm.nih.gov/pubmed/23335568). Rocuronium was implicated in 56% of cases, Vecuronium in 11% and Suxamethonium in 21%. Risk of anaphylaxis to Rocuronium was calculated as 8:100,000 exposures compared to 2.8:100,000 for Vecuronium. Apparently risk could not be calculated for Suxamethonium

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