Articles

Published on November 9th, 2012 | by Daniel Jolley

4

Neuromuscular myths: We need to do better

The rise of sugammadex has lead me down a path looking into wider aspects of my own neuromuscular blocking drug (NMBD) use. The evidence for NMBD use, monitoring and reversal is interesting, both for how consistently the same messages have been repeated over the past three decades — and for how little we have improved our practice in spite of mounting evidence demanding that we should. 1

I need to do better and you probably also need to do better with how we manage NMBDs.

This article was inspired by Fink & Hollman’s ‘Myths and facts in neuromuscular pharmacology’ 2

Myth 1: Post-operative residual curarisation (PORC) is uncommon

Several surveys of anesthetists show that we falsely consider the incidence of PORC in the post-anesthesia care unit to be very low. Videira surveyed anesthetists in Brazil who estimated the incidence of PORC at 5%, 3 while surveyed anesthetists and anesthesiologists in Europe and the US estimated the PORC incidence to be <1%. 4

The truth is quite different. Schreiber found a 27% incidence of a TOF ratio <0.9 after surgery between 60 and 90 minutes long. 5

A before-and-after audit by Bailard highlighted a drop in PORC from 62% to 3% of patients over a ten year period when a department improved quantitative neuromuscular monitoring of patients from 2% to 60% and the use of anti-cholinesterase reversal agents from 6% to 40% of patients. 6 The dramatic fall in PORC incidence should not over-shadow the persistence of the problem (3.5%) even in the presence of quantitative monitoring and routine reversal.

Videira also showed that anesthetists considered the prevalence of residual block much higher in their colleague’s practices than their own. This ‘illusory superiority’ (also called the ‘above average effect’) is a cognitive bias that leads us to overestimate the positive while underestimating our negative characteristics relative to others. 7 It is likely a core reason why non-evidence-based NMBD management persists in our specialty.


Myth 2: PORC is not clinically significant

Anesthetists argue that even if common, PORC is not clinically significant. The evidence suggests otherwise.

Back in 1997 Berg identified a correlation between pancuronium, PORC and post-operative pulmonary complications during six days of post-op follow-up. 8 Pancuronium-receiving patients with PORC (defined as TOFR < 0.7 in this study) suffered a three-times greater incidence of atelectasis, infiltrates and pneumonia than those without PORC — although there was no such increased incidence in those receiving atracurium or vecuronium.

Before we congratulate ourselves having moved away from pancuronium, more recent studies have focused on the intermediate NMBDs atracurium, vecuronium and rocuronium. Murphy showed that patients monitored by quantitative acceleromyography before extubation experienced less PORC, less desaturation below 90% (0% versus 21%) and less airway obstruction (0% versus 11%) during transport to the PACU. 9, 10

“The incidence, severity, and duration of hypoxemic events during the first 30 min of PACU admission were less in the acceleromyography group (all P < 0.0001).”

Lars Eriksson’s research group in Stockholm has shown that at a TOFR <0.9 there is pharyngeal dysfunction and increased aspiration risk, in addition to a depression of hypoxic and hypercarbic ventilatory responses. 11

“…partial paralysis cause pharyngeal dysfunction and increased risk for aspiration at mechanical adductor pollicis TOF ratios < 0.90. Pharyngeal function is not normalized until an adductor pollicis TOF ratio of > 0.90 is reached.” 12

“Partial neuromuscular paralysis caused by atracurium is associated with a four- to fivefold increase in the incidence of misdirected swallowing. … The majority of misdirected swallows resulted in penetration of bolus to the larynx.” 13

Kumar et al. showed that forced vital capacity and peak expiratory flow were both 20% lower, relatively, in patients with PORC compared to those with TOFR > 0.9 (13% and 9% in absolute terms). 14

“As respiratory muscle weakness results in ineffective cough and inability to clear secretions from airways, FVC recovery is considered important for preventing pulmonary complications.”

There is evidence that PORC is not free of consequences, although most patients likely escape significant complication. ‘Getting away with it’ is however not reason enough to ignore the problem. Surgical patients worldwide are now older, less fit, more obese, suffering a longer list of comorbidities and undergoing more complex surgery than ever before — each factor making PORC less physiologically tolerable.

Myth 3: Neuromuscular blocking drugs are predictable

Although the intermediate NMBDs such as vecuronium, atracurium, rocuronium and cisatrucurium provide greater reliability and improved kinetics over their predecessors, the recovery from neuromuscular blockade is still notoriously unpredictable.

Debaene et al. investigated residual paralysis in the PACU after a single intubating dose of intermediate NMBD in the absence of reversal. 15 They identified PORC (TOFR <0.9) in 45% of patients, with time since NMBD ranging from 30 to 400 minutes. In the subgroup of patients 2 hours after a single NMBD dose there was still a 37% incidence of PORC. Additionally there was very wide inter-patient variability, with PORC persisting more than 6 hours in three patients, and several patients with TOFR of only 0.2 after 2 hours. Other studies confirm the wide, unpredictable inter-patient variability of NMBD duration. 16

It is naive to believe it is safe to not reverse NMBDs after an arbitrary period, especially in the absence of objective neuromuscular monitoring.

“even after the administration of a single intubating dose of intermediate-acting muscle relaxant, quantitative assessment of TOF ratio is mandatory at the end of the surgical procedure to assess the presence or the absence of residual paralysis. At best, this measurement needs to be performed in the operating room rather than in the PACU to reverse the block before extubating…”

In Videira’s survey almost 70% of anesthetists did not believe antagonism was necessary if more than 60 minutes had passed after giving a NMBD. Videira rightly points out that this has little relevance when deciding whether pharmacological reversal is needed:

“Textbooks state that the duration of action of atracurium and rocuronium varies from 30 to 45 minutes. However … this concept expresses a return to a mechanomyographic response equivalent to 25% of the control value (T1/T0 ~ 25%) in single twitch stimuli that corresponds to an acceleromyographic T4/T1 (TOF) ratio of 0.1.”

Myth 4: Objective quantitative neuromuscular monitoring is unnecessary

Anesthetists who appreciate the importance of reversing neuromuscular blockade often still have misplaced confidence in their ability to clinically assess neuromuscular function. Videira identified that in addition to the interval since last NMBD, anesthetists commonly used the adequacy of spontaneous minute ventilation as a decision heuristic for deciding on the need for reversal.

“The adequacy of the breathing pattern was also cited heavily … This visual cue may be erroneously interpreted as a sufficient sign for tracheal extubation, instead of a necessary one. This heuristic assesses function of the diaphragm, not of the upper airway muscles.”

Other clinical tests of PORC are also inadequate, whether lifting limbs or opening eyes. The 5-second Head Lift Test and the Tongue Depressor Test, often used to detect PORC in the PACU are of limited use for detecting TOFR < 0.9, having sensitivities of only 11% and 13% and specificities of 87% and 90% respectively.15 The Head Lift Test cannot identify POCR with a TOFR > 0.5. Debaene’s study population demonstrated Positive and Negative Predictive Values of the Head Lift and Tongue Depressor Tests of only 53-58%!

Subjective, qualitative neuromuscular monitors fare no better: Tactile TOF Fade and Double Burst Stimulation (DBS) have similar sensitivities (11% and 13% respectively), although high specificities (99% each). This provides a good Positive Predictive Value (93% & 97%) but a very poor Negative Predictive Value (57% & 58%) (depending on the incidence of PORC).15

Unfortunately a survey of anesthetists and anaesthesiologists in both Europe and the US in 2010 showed disappointingly low rates of quantitative neuromuscular monitoring: half of the anesthetists in Europe and only 20% in the US regularly monitored quantitative TOFR. 20% of Europeans and almost 10% of Americans never use neuromuscular monitors.

Neither clinical tests, clinical experience nor a visual or tactile train of four assessment will detect PORC with reliable accuracy. The weight of evidence asserts that objective quantitative neuromuscular monitoring be mandatory whenever a patient is paralysed.

Myth 5: Sugammadex will make PORC a problem of the past

The most recent interest in PORC has been stimulated by the appearance of sugammadex. The unique nature of sugammadex as a true reversal agent for aminosteroid NMBDs, such as rocuronium, offers hope that PORC may be avoidable altogether. This hope needs be tempered by one point:

  • We already possess the knowledge, pharmacology (neostigmine) and technology (objective quantitative neuromuscular monitors) to dramatically reduce the incidence of PORC, yet have not. PORC occurs not because of our lack of ability but because of our practice and behaviour — our lack of will. The ability to reverse one class of NMBDs with sugammadex will not magically change our willingness to do so.

The greater reliability, faster speed of onset and lesser inter-patient variability of sugammadex compared with the anticholinesterases may very likely reduce PORC incidence. Case reports of sugammadex’s use in neuromuscular disorders normally at high risk of residual paralysis are certainly very positive. 17 However the existence of sugammadex is unlikely to dramatically change anaesthetist behaviour, and it is still too early to know the true impact of sugammadex on residual paralysis.

We need to look at our practice

Perhaps you are already a regular user of quantitative neuromuscular monitors — if so, great! But if like many you are not; or if you believe that good spontaneous minute volumes two hours after a single dose of atracurium mean that you don’t need to reverse — then it may be beneficial to have a closer look at your neuromuscular practice.

I know I will.

The case for routine quantitative neuromuscular monitoring
Quality of Evidence www.dyerware.comwww.dyerware.comwww.dyerware.comwww.dyerware.comwww.dyerware.com
High quality evidence somewhat hampered by the evolution of the definition of PORC and the progress of neuromuscular pharmaceuticals over the past 30 years. Most recent outcome evidence relies on surrogate markers of patient harm.
Quantity of Evidence www.dyerware.comwww.dyerware.comwww.dyerware.comwww.dyerware.comwww.dyerware.com
Large amounts of evidence covering three generations of NMBDs and spanning three decades of anesthetic practice.
In Real Life www.dyerware.comwww.dyerware.comwww.dyerware.comwww.dyerware.comwww.dyerware.com
Objective neuromuscular monitoring is non-invasive, simple, effective and essentially risk free. Requires access to quantitative neuromuscular monitor.
Overall Practice Changing Strength www.dyerware.comwww.dyerware.comwww.dyerware.comwww.dyerware.comwww.dyerware.com
The weight of evidence strongly supports routine monitoring of neuromuscular function, with little risk yet likely significant benefit — especially for older patients or those with comorbidities.

 

Do you think we need to do better with our neuromuscular practice? Leave a comment below.

 

Notes:

  1. Case in point: Donati F. Neuromuscular monitoring: what evidence do we need to be convinced? Anesth Analg. 2010 Jul;111(1):6-8. (pubmed)
  2. Fink H, Hollmann MW. Myths and facts in neuromuscular pharmacology. New developments in reversing neuromuscular blockade. Minerva Anestesiol. 2012 Apr;78(4):473-82.
  3. Videira RL, Vieira JE. What rules of thumb do clinicians use to decide whether to antagonize nondepolarizingneuromuscular blocking drugs? Anesth Analg. 2011 Nov;113(5):1192-6.
  4. Naguib M, Kopman AF, Lien CA, Hunter JM, Lopez A, Brull SJ. A survey of current management of neuromuscular block in the United States and Europe. Anesth Analg 2010;111:110–9
  5. Schreiber JU, Mucha E, Fuchs-Buder T. Residual paralysis following a single dose of atracurium: results from a quality assurance trial. Eur J Anaesthesiol. 2010 Nov;27(11):993-4.
  6. Baillard C, Clec’h C, Catineau J, Salhi F, Gehan G, Cupa M, Samama CM. Postoperative residual neuromuscular block: a survey of management. Br J Anaesth. 2005 Nov;95(5):622-6.
  7. The above average effect has been identified in many areas, from academic performance to driving ability. Related to this is the Dunning-Kruger effect whereby those with the lowest skill in an area have the least insight into how their skill level compares with others.
  8. Berg H, Roed J, Viby-Mogensen J, Mortensen CR, Engbaek J, Skovgaard LT, Krintel JJ. Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand. 1997 Oct;41(9):1095-1103.
  9. Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS, Nisman M. Intraoperative acceleromyographic monitoring reduces the risk of residual neuromuscular blockade and adverse respiratory events in the postanesthesia care unit. Anesthesiology. 2008 Sep;109(3):389-98.
  10. Murphy’s methodology has been quite rightfully criticised for using subjective ‘visual TOFR’ as the control. Nonetheless the results stand as a demonstration of a correlation between an increased incidence of PACU pulmonary complication and PORC.
  11. Eriksson LI. Reduced hypoxic chemosensitivity in partially paralysed man. Acta Anaesthesiol Scand. 1996 May;40(5):520-3.
  12. Eriksson LI, Sundman E, Olsson R, Nilsson L, Witt H, Ekberg O, Kuylenstierna R. Functional assessment of the pharynx at rest and during swallowing in partially paralyzed humans: simultaneous videomanometry and mechanomyography of awake human volunteers. Anesthesiology. 1997 Nov;87(5):1035-43.
  13. Sundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R, Eriksson LI. The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium. Anesthesiology. 2000 Apr;92(4):977-84.
  14. Kumar GV, Nair AP, Murthy HS, Jalaja KR, Ramachandra K, Parameswara G. Residual Neuromuscular Blockade Affects Postoperative Pulmonary Function. Anesthesiology. 2012 Oct 19;
  15. Debaene B, Plaud B, Dilly MP, Donati F. Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. Anesthesiology. 2003 May;98(5):1042-8.
  16. Maybauer DM, Geldner G, Blobner M, Pühringer F, Hofmockel R, Rex C, Wulf HF, Eberhart L, Arndt C, Eikermann M. Incidence and duration of residual paralysis at the end of surgery after multiple administrations of cisatracurium and rocuronium. Anaesthesia. 2007 Jan;62(1):12-7
  17. Stewart PA, Phillips S, De Boer HD. Sugammadex reversal of rocuronium-induced neuromuscular blockade in two types of neuromuscular disorders: Myotonic dystrophy and spinal muscular atrophy Rev Esp Anestesiol Reanim. 2012 Sep 1.

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About the Author

is an Australian consultant anaesthetist/anesthesiologist, with interests in anaesthesia education, obstetric and paediatric anaesthesia, and the practice of anaesthesia in remote and under-resourced environments. Daniel trained in Sydney, Darwin and Melbourne, and has worked in Sydney, Melbourne, Darwin, Fiji and Mongolia. He is one of the founders of gasexchange.com along with Brad O'Connor.


4 Responses to Neuromuscular myths: We need to do better

  1. gdoolan says:

    Why are the qualitative double burst and train of four so bad at picking up significant residual paralysis?

    Presumably if you are going to reverse the patient anyway you don’t need the fancy quantitative monitors. This would be an issue currently, as these monitors are rare in hospitals in Melbourne.

    I reverse everyone, unless there is some specific reason not to. I usually use TOF at the facial nerve to decide whether the patient is ready to be reversed, as the hands are usually under the drapes somewhere. Anyone else do this, and what are the traps?

  2. Very, very good questions.

    1. Qualitative TOF and DBS rely on tactile (or even worse, visual) detection of fade by the anesthetist. Fade is not detectable by tactile means above TOFR 0.5 (so most PORC will be missed) — even if the anaesthetist is very experienced: Tactile and visual evaluation of the response to train-of-four nerve stimulation. DBS improves this (perhaps to detect TOFR < 0.6) though you still miss an unacceptable amount of PORC: Manual evaluation of residual curarization using double burst stimulation: a comparison with train-of- four. This study showed DBS tactile-fade was detected only in 60% of subjects at TOFR < 0.6, and only 30% at TOFR 0.7. [note that both these studies are over 20 years old, so we have little excuse to (still) be using qualitative neuromuscular monitors — why has the importance of quantitative monitoring not been emphasized in anesthesia training?!] 2. It has also been my practice to routinely reverse everyone, unless specifically contraindicated (rare). I must now concede this is poor practice and I need to change, for two reasons: a. The main problem with anti-cholinesterase reversal is that it has a ceiling effect — beyond a certain depth of neuromuscular blockade, even completely inhibiting acetylcholinesterase will not result in enough acetylcholine to sufficiently compete with the NMBD at acetylcholine receptors. Thus if you have a patient who falls at one end of the NMBD-recovery spectrum, they may not even be reversible when you give neostigmine. At best, your standard reversal dose of neostigmine 20 mcg/kg (we all give each adult patient a calculated individualized-dose, right...?) will not sufficiently reverse them to a TOFR of 0.9 where they are able to reliably protect their airway from aspiration. (see ref. 13 above) b. Once 'reversed' (either by neostigmine or enough clearance of sufficient NMBD) then anticholinesterase action is actually detrimental — in fact, if we increase neuromuscular junction Ach enough in the absence of competitive inhibition with a NMBD, we start to get muscle weakness from a depolarizing effect, similar to suxamethonium. Additionally it was recently shown that there are negative clinical consequences to giving neostigmine in the absence of a block: Neostigmine/glycopyrrolate administered after recovery from neuromuscular block increases upper airway collapsibility by decreasing genioglossus muscle activity in response to negative pharyngeal pressure.

    So the reason that we must quantitatively monitor the level of block for all patients is that recovery of blockade is much less predictable than we have been taught (or chosen to believe). Without an objective monitor most patients will still probably be okay, but a portion will fall at either end of the curve: either a standard ‘one ampoule’ reversal dose will not be enough, or it will be too much. Either way they suffer impaired muscle function and risk respiratory complications: atelectasis, aspiration, pneumonia…

    Regarding site of monitoring of the TOF, both orbicularis oculi and adductor pollicis are only surrogates for pharyngeal muscle tone. Orbicularis oculi monitoring tends to under-estimate the degree of block, so risks missing PORC. In fact Thilen et al. showed a five-fold increase in PORC when eye muscles were used for monitoring compared with the hand: Intraoperative neuromuscular monitoring site and residual paralysis.

    “Patients having qualitative TOF monitoring of eye muscles had a greater than 5-fold higher risk of postoperative residual paralysis than those monitored at the adductor pollicis.”

    To top things off, another study highlighting the need for quantitative monitoring was just published in the BJA: Grosse-Sundrup M, et al. Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications. BMJ. 2012 Oct 15;345.

    “The use of intermediate acting neuromuscular blocking agents during anesthesia was associated with an increased risk of clinically meaningful respiratory complications.”

    We all need to have a closer look at how we manage NMBDs.

  3. torrag says:

    I believe that if you have not been burned either by roc or vec once, then, it is just a matter of time. During residency I used a lot of cisatracurium and never got burned once. For the longest time, I believe that death, taxes and nimbex recovery were guarantees in life. After reading this page and looking over Debaene et al. NMBD study, along with other studies comparing atracurium vs nimbex recovery profiles (similar), I may have to change my beliefs. Has anybody here has had problems with cisatracurium and recovery?

    It may not be an ideal agent to achieve ideal laryngoscopy views (large amounts required), but, for maintenance, I still like it the best. That said, we do not carry it in my current practice (cost issue).

  4. torrag, thanks for your comment! I too had a similar faith in the predictable recovery of atracurium, though after investigating the issue for this article my confidence has been undermined. I have only had a couple of occasions where atracurium (not cisatracurium / Nimbex ®) reversal was clinically an unexpected problem — though suspect that we miss lot of incomplete-reversal. Of course the clinical significance of this in terms of outcome is ill defined.

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Notes:

  1. Case in point: Donati F. Neuromuscular monitoring: what evidence do we need to be convinced? Anesth Analg. 2010 Jul;111(1):6-8. (pubmed)
  2. Fink H, Hollmann MW. Myths and facts in neuromuscular pharmacology. New developments in reversing neuromuscular blockade. Minerva Anestesiol. 2012 Apr;78(4):473-82.
  3. Videira RL, Vieira JE. What rules of thumb do clinicians use to decide whether to antagonize nondepolarizingneuromuscular blocking drugs? Anesth Analg. 2011 Nov;113(5):1192-6.
  4. Naguib M, Kopman AF, Lien CA, Hunter JM, Lopez A, Brull SJ. A survey of current management of neuromuscular block in the United States and Europe. Anesth Analg 2010;111:110–9
  5. Schreiber JU, Mucha E, Fuchs-Buder T. Residual paralysis following a single dose of atracurium: results from a quality assurance trial. Eur J Anaesthesiol. 2010 Nov;27(11):993-4.
  6. Baillard C, Clec’h C, Catineau J, Salhi F, Gehan G, Cupa M, Samama CM. Postoperative residual neuromuscular block: a survey of management. Br J Anaesth. 2005 Nov;95(5):622-6.
  7. The above average effect has been identified in many areas, from academic performance to driving ability. Related to this is the Dunning-Kruger effect whereby those with the lowest skill in an area have the least insight into how their skill level compares with others.
  8. Berg H, Roed J, Viby-Mogensen J, Mortensen CR, Engbaek J, Skovgaard LT, Krintel JJ. Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand. 1997 Oct;41(9):1095-1103.
  9. Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS, Nisman M. Intraoperative acceleromyographic monitoring reduces the risk of residual neuromuscular blockade and adverse respiratory events in the postanesthesia care unit. Anesthesiology. 2008 Sep;109(3):389-98.
  10. Murphy’s methodology has been quite rightfully criticised for using subjective ‘visual TOFR’ as the control. Nonetheless the results stand as a demonstration of a correlation between an increased incidence of PACU pulmonary complication and PORC.
  11. Eriksson LI. Reduced hypoxic chemosensitivity in partially paralysed man. Acta Anaesthesiol Scand. 1996 May;40(5):520-3.
  12. Eriksson LI, Sundman E, Olsson R, Nilsson L, Witt H, Ekberg O, Kuylenstierna R. Functional assessment of the pharynx at rest and during swallowing in partially paralyzed humans: simultaneous videomanometry and mechanomyography of awake human volunteers. Anesthesiology. 1997 Nov;87(5):1035-43.
  13. Sundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R, Eriksson LI. The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium. Anesthesiology. 2000 Apr;92(4):977-84.
  14. Kumar GV, Nair AP, Murthy HS, Jalaja KR, Ramachandra K, Parameswara G. Residual Neuromuscular Blockade Affects Postoperative Pulmonary Function. Anesthesiology. 2012 Oct 19;
  15. Debaene B, Plaud B, Dilly MP, Donati F. Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. Anesthesiology. 2003 May;98(5):1042-8.
  16. Maybauer DM, Geldner G, Blobner M, Pühringer F, Hofmockel R, Rex C, Wulf HF, Eberhart L, Arndt C, Eikermann M. Incidence and duration of residual paralysis at the end of surgery after multiple administrations of cisatracurium and rocuronium. Anaesthesia. 2007 Jan;62(1):12-7
  17. Stewart PA, Phillips S, De Boer HD. Sugammadex reversal of rocuronium-induced neuromuscular blockade in two types of neuromuscular disorders: Myotonic dystrophy and spinal muscular atrophy Rev Esp Anestesiol Reanim. 2012 Sep 1.
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