Muscle relaxants

Muscle relaxants

Comparison of the advantages and disadvantages of rocuronium versus suxamethonium in the setting of rapid sequence induction of anaesthesia in a retrieval setting

OrRoc rocks and Sux sucks

Apologies to any anaesthetists present

Closer to this level

Few weeks ago Flew into Quairading

53 year old male, 130 kg with asthma

History of NIDDM, 30 cpd smoker

Stable airport pick up

Patient arrived at airstrip not quite so stable

Things went downhill quickly Quickly transferred him to the aircraft on NRB, then even more quickly

transferred him back off it!

Agitated, sats 85-90%, P120, bilateral creps, hypotensive, on iv salbutamol

BiPaP applied in hanger, transferred back to hospital

Noted ECG to have elevation in aVr and widespread ST depression anterlaterally

CO2 78 HCO3 suggested mostly chronic

Noted cpap machine in patients bag later

What next? Transfer on BiPaP versus RSI in remote location?

Failing on BiPaP

Not adequately preoxygenated

Likely difficult airway

Possibly hard to bag valve mask ventilate

Decision to RSI Which induction agent?

Which muscle relaxant?

History of muscles relaxants First encountered by Europeans in the 16 century in the amazon basin with

the use of curare tipped darts

Tubocurare was most active of these poisons, but was not really established in anaesthetic practice until 1943

Depolarizing agents Acetylcholine

Succinylcholine (suxamethonium)

Decamethonium

Small molecules , can enter NMJ

Non depolarizing agents Aminosteroids eg.pancuronium, vecuronium, rapacuronium, dacuronium,

maloutine, duador, dipyrandium, pipecuronium

Tetrahydroisoquinoline derivatives atracurium, mivacurium, doxacurium, tubocurare

Gallamine

And for real bush doctors Death adder

Blue ringed octopus

Puffer fish/blow fish

Our choices Vecuronium

Rocuronium

suxamethonium

rocuronium Dose adult RSI 0.6 – 1.2 mg/kg

Duration of action 30 to 90 minutes

BMI >40 use ideal body weight x 1.2 mg / kg, provides good or excellent intubation conditions at 60 seconds ( Gaszynski 2011)

Tracheal intubation (not RSI) 0.3 or 0.45 – 0.6 mg /kg

Can be used for ongoing paralysis 0.1 – 0.2 mg/ kg bolus prn or 10 – 12 mcg/kg/min

Children same dose onset time reduces as dose increases, however not recommended by manufacturer, however successfully used in children > 1 year (Chong 2002, Fuchs-Buder 1996, Mazurek 1998, Naguib 1997)

Rocuronium continues Geriatric dose , same

Renal impairment, same dose , duration may vary

Hepatic impairment, no dose change advised from manufacturer, however ascites may result in need for dose at higher end of range and duration may be increased

Stable in D5NS, D5, RL, NS

Not incompatible with anything we have (mitafungin!)

Adverse reactions Cardiovascular , increased peripheral vascular resistance, tachycardia (< 5%,

incidence greater in children), hypertension, transient hypotension

Hypersensitivity <1%

Contraindications hypersensitivity to rocuronium , any component thereof or other neuromuscular blocking drugs

Roc, disease related concerns Burn injury , resistance may occur if > 20 % TBSA(Han 2009)

CV disease, use with caution, action may be delayed and duration prolonged

Conditions that antagonize neuromuscular blockade: resp alkalosis, hypercalcaemia, demyelinating lesions, peripheral neuropathies may antagonize NM blockade (Greenberg 2013, Miller 2010, Naguib 2002)

Conditions that potentiate NM blockade, v low Ca , low K, cachexia, NM disease, pH disturbances, myasthenia gravis

Pulmonary hypertension, may increase PVR

Suxamethonium Depolarizing muscle relaxant

Iv 1- 1.5 mg/kg, can be used IM

Obesity use total body weight

Renal imapirment no dosage adjustment

Hepatic impairment no dosage adjustments

Compatibility, stable in all common fluids, but incompatible with thiopentone

Does have a few little problems though Cardiovascular: arrhythmias, bradycardia, cardiac arrest, hyper/hypotension,

tachycardia

Dermatologic: rash

Metabolic: hyperkalaemia (check K first and all will be well?)

Gastrointesinal: salivation (excessive)

Neuromuscular and skeletal, jaw rigidity, muscle fasciculation, post operative muscle pain, rhabdomyolysis (with possible myoglobinuric renal failure)

And the rest Ocular: increased intraoccular pressure

Resp: sux apnoea

Miscellaneous: anaphylaxis, malignant hyperthermia

Case reports: acute quadriplegic myopathy syndrome, myositis ossificans (prolonged use)

Case report of hyperkalaemic arrest Piotrowski et al. Paed critical care Med 2007: vol8 no2

Hyperkalaemia and cardiac arrest following succinylcholine administration in a 16 year old boy with acute non lymphoblastic leukaemia and sepsis

Pre induction K 3.1 mmol

30 minutes post sux cardiac arrest K 8.64 mmol

90 minutes later (survived) K 3.8 mmol/l

Contraindications from up to date Hypersensitivity to sux, or any part thereof

Personal or family history of malignant hyperthermia

Myopathies associated with a raised CK

Acute phase injury following major burns

Multiple trauma !!!

Extensive denervation of skeletal muscle or upper motor neurone injury

Sux disease related concerns (utd) Burns : high risk 7-10 days

Conditions which may antagonize NMB: alkalosis, hypercalcaemia, demyelinating lesions, peripheral neuropathies, denervation, infection, muscle trauma and DM

Conditions which may potentiate NMB: electrolyte abnormalities, severe low Na, Low Ca, low K, high Mg, NM disease, acidosis, porphyria, myaesthenia gravis, Eaton Lambert, renal failure and hepatic failure

Plasma pseudocholinesterase disorders

Sux drug interactions (utd) abobbotulinumtoxinA, Acetylcholinesterase inhibitors, Aminoglycosides

Analgesia, may increase the bradycardic effect of opiodes

Bambuterol, clindamycin, cyclophosphamide, cyclosporin, echothiophate

Lincosamide antibiotics, lithium, loop diuretics (diminish effect), magnesium salts, phenelzine, polymyxin B, procainamide, quinidine

Tetracycline derivative

Vancomycin most of these will enhance effect

If they both new drugs which would you choose?

Advantages of Rocuronium Few side effects

Few/ no real contraindications

Predictable dose dependent kinetics

Safe in burns, hyperkalaemia, renal failure, hepatic failure, denervation conditions

Longer duration of action *

Disadvantages of rocuronium Unfamiliarity

Price

Duration of action *

Advantages of suxamethonium Rapid onset <60 seconds

Possibly less anaphylaxis

Can visualize onset with cessation of fasciculation

Cheap

Short acting, may wear off in time in can’t intubate can’t ventilate scenario

Familiar, so why change

Easy to spot contra-indications to sux

disadvantages Burns

Hyperkalaemia

Denervation conditions, MS

Autonomic instability

Crush injuries

Malignant hyperthermia

Masseter spasm

Sux disadvantages continued Bradycardia, increased with second dose or children, incidence reduced

with atropine

Increased intraoccular pressure, use with caution in narrow angle glaucoma or penetrating eye injury

Vagal tone may be increased

So let’s look at those advantages of sux First rapid onset

Sluga et al,Anaesth Analg. 2005: 101:1356-61, prospective study

Compared 0.6 mg /kg rocuronium with 1 mg / kg suxamethonium

They found that suxamethonium had a statistically significant improvement on intubating conditions at 60 seconds

So far so good?

McCourt et al, Anaesthesia 2006; 101:1356-61 Compared roc 0.6 mg/kg, 1.0 mg/kg and sux 1.0 mg/kg, ? blinded

Found 1.0 mg/kg better than 0.6 mg/kg of rocuronium at 50 seconds

Comparison of the rocuronium 1.0 mg/kg group and the sux 1.0 mg/ kg group revealed had similar frequency of acceptable intubating conditions at 50 seconds

However there was a higher incidence of “excellent” intubating conditions in the sux 1.0 mg/kg group

Lauren et al, Acad Emerg Med 2000; 7:1362-9 Basically found the same

They used the same rocuronium doses but 1.7 mg /kg suxamethonium

so far so good?

however Patanwala et al, Comparison of succinylcholine and rocuronium for first

attempt intubation success in the emergency department. Acad Emerg Med. 2011; 18:11-14

Retrospective analysis

Compared a mean dose of 1.65 mg/kg of sux (n=113) and roc mean 1.19 mg/kg

“no difference at success rate for first intubation attempt or number of attempts regardless of the type of paralytic used or the dose administered.”

Then Cochrane chipped in their 2 cents worth in 2008 “rocuronium versus succinylcholine for rapid sequence induction”

Combined 37 studies

Concluded “no statistical difference in intubating condition when [suxamethonium] was compared to 1.2 mg/kg of rocuronium”

So let’s review the advantages of sux

Advantages of suxamethonium Rapid onset <60 seconds X

Possibly less anaphylaxis


Cheap




Next risk of anaphylaxis Rose et al. Rocuronium: high risk for anaphylaxis? Br J Anaesth. 2001; 86(5):

678-82

Concluded the incidence of anaphylaxis to any NMJ blocking drug is proportional to its market share

The authors concluded rocuronium should be considered an “intermediate risk” for anaphylaxis, compared to suxamethonium which is “high risk”


Possibly less anaphylaxis X


Cheap




Lets knock an easy one off next Contra indications to sux are easy to spot

Unless you can see the potassium level I’m going to call b******t on this one

As we’ve already seem a normal K doesn’t ensure your patient won’t have a hyperkalaemic arrest shortly afer induction




Cheap



Easy to spot contra-indications to sux X

However sux is still safer, right? Many clinicians believe that by using sux the have inserted a safety margin

into their RSI protocol

Only lasts 5 to 10 minutes

NMB may wear off and patient will spontaneously breath, and all will be well, and they all lived happily ever after…….

Whereas roc will last 30-90 minutes

Heier et al. Desaturation after succinylcholine-induced apnoea. Anaesthesiology 2001;94.754-9

12 healthy volunteers aged 18 -45

All pre-oxygenated to end-tidal O2 > 90%, after 3 mins FiO2 1.0

Administration of thiopentone and sux @1mg/kg

No assisted ventilation

1/3 desaturated to <80 %, then BVM

This is not our usual patient cohort

Neguib et al. Succinylcholine dosage and apnoea induced haemoglobin desauration in patients. Anaesthesiology. 2005;b102(1)35-40

Similar experiment

Except used 0.6 mg /kg sux instead of 1.0 mg/kg

Found SpO2 desaturation to <90% in 65 % (was 85 % in Heier study)

Did not however shorten time to spontaneous diaphragmatic movement

Therefore probably doesn’t support the “might be safer as will breathe yourself” theory




Cheap

Short acting, may wear off in time in can’t intubate can’t ventilate scenario X



well at least its cheap

Generic, US prices

Rocuronium 100mg $8.51 US

Suxamethonium 100 mg as cheap as $2 US

Potential saving of over $6 US, it all adds up

Except You have to buy a fridge to keep the sux in

After 10 minutes you will have to spend a further $6 dollars US ( the $6 you saved on the last slide) on a 10 mg vial of vecuronium

So only cheaper if you already own a fridge and you are sure your patient will not be requiring NMB in 15 minutes, so either fully recovered or dead.




Cheap X

Short acting, may wear off in time in can’t intubate can’t ventilate scenario X



Disadvantages of rocuronium Unfamiliarity

Price X

Duration of action * X

So that leaves 3 good reasons to use sux You like watching fasciculations

You are familiar with sux and don’t want to change

Your patient has no contraindications to sux, will not require NMB in 15 minutes time and you desperately need to save $6, and you already own a fridge.

For those of you that love fasciculations Rate of desaturation is an issue

Fasciculations use oxygen and this may increase rate of desaturation

This was explored by Taha et al.Effect of suxamethonium vs rocuronium on onset of oxygen saturation during apnoea following rapid sequence induction. Anaesthesia 2010,65:358-361

methods 3 groups

Lidocaine/fentanyl/rocuronium, lidocaine/fentanyl/suxamethonium, propofol/suxamethonium

Measured time to reach sats of 95%

Both sux groups desaturated significantly quicker than roc group

Lidocaine/ fentanyl took longer than propfol group

Another study backs this up Tang et al. Desaturation following rapid sequence induction using succinylcholine vs

rocuronium in overweight patients. Act Anaesthesiology scand. 2011; 55:203-6

BMI of 25-30 undergoing elective surgery

Either 1.5 mg /kg sux or 0.9 mg/kg rocuronium

No assisted ventilation until sats <92%

Measured time to get to 92%, then measured the time to sats >97% with assisted ventilation

Results desaturated faster with sux, and took longer to recover sats to 97%

Scared of a little commitment?

Sugammadex, (for those without the courage of their convictions) Effective reversal for rocuronium

Gamma cyclodextrin that enccapsulates rocuronium

Lee et al. Reversal of profound neuromuscular block by sugammadex administered 3 minutes after rocuronium. Anaesthesiology. 2009; 110:1020-5

1.2 mg / kg of rocuronium given

Then at 3 minutes 16 mg /kg of sugammadex given

Mean time to 1st twitch on To4 4.4 minutes for roc, 7.1 minutes for sux

Another study De Boer, Anaesthesiology.2007; 107: 239-44 found the mean recovery to 90 % at 1.9 minutes

Is a long duration of action a good or a bad thing? Encourages definite plan to take control

Possibly reduces incidence of “can’t ventilate” situations

Our cohort of patients waking up is not usually an option

Removes the need for adding a non depolarizing agent in the 10 minutes post induction, when everything is happening

Going back to the Quairading patient Choice of muscle relaxant?

One good reason left to use sux You don’t want to change

They both do the job, both reasonable options

Muscle relaxants

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