Muscle relaxants

Muscle relaxants

1. 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

2. Or Roc rocks and Sux sucks

3. Apologies to any anaesthetists present

4. Closer to this level

5. 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

6. 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

7. 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

8. Decision to RSI Which induction agent? Which muscle relaxant?

9. History of muscles relaxants First encountered by E uropeans 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

10. Depolarizing agents Acetylcholine Succinylcholine ( suxamethonium ) Decamethonium Small molecules , can enter NMJ

11. Non depolarizing agents Aminosteroids eg. pancuronium , vecuronium , rapacuronium , dacuronium , maloutine , duador , dipyrandium , pipecuronium Tetrahydroisoquinoline derivatives atracurium , mivacurium , doxacurium , tubocurare Gallamine

12. And for real bush doctors Death adder Blue ringed octopus Puffer fish/blow fish

13. Our choices Vecuronium Rocuronium suxamethonium

14. 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)

15. 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 !)

16. 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

17. 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

18. 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

19. 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)

20. And the rest Ocular: increased intraoccular pressure Resp : sux apnoea Miscellaneous: anaphylaxis, malignant hyperthermia Case reports: acute quadriplegic myopathy syndrome, myositis ossificans (prolonged use)

21. 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

22. 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

23. 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

24. 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

25. If they both new drugs which would you choose?

26. 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 *

27. Disadvantages of rocuronium Unfamiliarity Price Duration of action *

28. 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

29. disadvantages Burns Hyperkalaemia Denervation conditions, MS Autonomic instability Crush injuries Malignant hyperthermia Masseter spasm

30. 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

31. 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?

32. 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

33. 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?

34. 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.”

35. 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

36. Advantages of suxamethonium Rapid onset <60 seconds X 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

37. 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”

38. Advantages of suxamethonium Rapid onset <60 seconds X Possibly less anaphylaxis X 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

39. 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

40. Advantages of suxamethonium Rapid onset <60 seconds X Possibly less anaphylaxis X 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 X

41. 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

42. 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

43. 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

44. Advantages of suxamethonium Rapid onset <60 seconds X Possibly less anaphylaxis X Can visualize onset with cessation of fasciculation Cheap Short acting, may wear off in time in can’t intubate can’t ventilate scenario X Familiar, so why change Easy to spot contra-indications to sux X

45. 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

46. 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.

47. Advantages of suxamethonium Rapid onset <60 seconds X Possibly less anaphylaxis X Can visualize onset with cessation of fasciculation Cheap X Short acting, may wear off in time in can’t intubate can’t ventilate scenario X Familiar, so why change Easy to spot contra-indications to sux X

48. Disadvantages of rocuronium Unfamiliarity Price X Duration of action * X

49. 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.

50. 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

51. 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

52. 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%

53. Scared of a little commitment?

54. 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 1 st 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

55. 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

56. Going back to the Quairading patient Choice of muscle relaxant?

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

58. They both do the job, both reasonable options