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.
What is PORC?
Post-operative residual curarisation (PORC) or residual paralysis, refers to persisting neuromuscular blockade in a patient after extubation. It is considered present when the Train-of-four (TOF) ratio is less than 0.9, usually measured in recovery or the post anesthesia care unit (PACU).
The historical comparison of studies investigating PORC is difficult because for many years a TOF ratio of 0.7 was considered the cutoff value for PORC. Volunteers given d-tubocurarine had normal vital capacity and inspiratory force when the TOFR recovered above 0.7. Then in the mid-1990s a TOF ratio of 0.8 was used in studies investigating PORC.
Now in the 21st century a TOFR 0.9 is considered the cut-off for defining PORC. A TOFR 0.9 has been chosen because consequences of residual paralysis, such as pharyngeal dysfunction and impairment of respiratory function have been shown below this TOF ratio.
This article was inspired by Fink & Hollman's "Myths and facts in neuromuscular pharmacology".2 An up-to-date collection of articles related to post-op residual curarisation can be found here: Neuromuscular myths: the lies we tell ourselves.
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
★ ★ ★ ★ ☆
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
★ ★ ★ ★ ★
Large amounts of evidence covering three generations of NMBDs and spanning three decades of anesthetic practice.
In Real Life
★ ★ ★ ★ ☆
Objective neuromuscular monitoring is non-invasive, simple, effective and essentially risk free. Requires access to quantitative neuromuscular monitor.
Overall Practice Changing Strength
★ ★ ★ ★ ☆
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.
Case in point: Donati F. Neuromuscular monitoring: what evidence do we need to be convinced? Anesth Analg. 2010 Jul;111(1):6-8. (pubmed) ↩
Fink H, Hollmann MW. Myths and facts in neuromuscular pharmacology. New developments in reversing neuromuscular blockade. Minerva Anestesiol. 2012 Apr;78(4):473-82. ↩
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. ↩
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 ↩
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. ↩
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. ↩
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. ↩
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. ↩
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. ↩
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. ↩
Eriksson LI. Reduced hypoxic chemosensitivity in partially paralysed man. Acta Anaesthesiol Scand. 1996 May;40(5):520-3. ↩
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. ↩
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. ↩
Kumar GV, Nair AP, Murthy HS, Jalaja KR, Ramachandra K, Parameswara G. Residual Neuromuscular Blockade Affects Postoperative Pulmonary Function. Anesthesiology. 2012 Oct 19; ↩
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. ↩
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 ↩
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. ↩