Residual Paralysis after Emergence from Anesthesia

SEVERAL studies have documented that neuromuscular block often persists in the postanesthesia care unit (PACU), even with the administration of acetylcholinesterase inhibitors. The frequency of this phenomenon, which has been called “residual curarization,”“residual neuromuscular block,”“postoperative residual curarization,” or “residual paralysis,” ranges between 4 and 50% depending on the diagnostic criteria, the type of nondepolarizing neuromuscular blocking drug (NMBD), the administration of a reversal agent, and, to a lesser extent, the use of neuromuscular monitoring. The problem is obviously clinically relevant, because residual paralysis after emergence from anesthesia (henceforth referred to as residual paralysis) is associated with muscle weakness, oxygen desaturation, pulmonary collapse, and acute respiratory failure that could lead to severe permanent brain damage or death. Despite extensive documentation of such residual paralysis in the literature, awareness of its clinical consequences remains surprisingly limited, and the use of NMBDs, neuromuscular monitoring, and reversal agents are dictated more by tradition and local practices than by evidence-based medicine.Residual paralysis is associated with postoperative complications such as hypoxia, weakness, and respiratory failure. However, these complications may have many other causes so that the role of neuromuscular block is often unrecognized. Thus, it is important to manage neuromuscular block rationally and have a sound strategy to prevent, diagnose, and treat residual paralysis. This can be accomplished by adhering to simple and consistent guidelines not only before tracheal extubation but also throughout the surgical procedure. The data in the current literature on residual paralysis were obtained with acetylcholinesterase inhibitors as the only agents available to accelerate neuromuscular recovery. Reassessment of practice in this regard is relevant now that sugammadex, a selective binding agent, has become available in certain parts of the world.Absence of residual paralysis means that neuromuscular transmission has recovered sufficiently, and so the unaided patient can breathe normally, clear secretions, cough, prevent aspiration of gastric contents, and maintain a patent upper airway. Because this return to complete recovery cannot be assessed easily before emergence from anesthesia and even during the early postanesthesia recovery phase, anesthesiologists have to rely on surrogate measurements. With the introduction, in the early 1970s, of the train-of-four (TOF) stimulation applied to the ulnar nerve, it became necessary to correlate adductor pollicis response to indices of respiratory function (fig. 1). In a study conducted by Ali et al. 1on six healthy awake volunteers, vital capacity, inspiratory force, and expiratory force were found to be normal when TOF ratio (TOFR; the ratio of the fourth to the first twitch height) was more than or equal to 0.70.Based on that evidence, the 0.7-TOFR threshold was considered to indicate adequate neuromuscular recovery for nearly two decades. However, in the 1990s, several lines of evidence indicated that clinically relevant neuromuscular block still persists at TOFR = 0.7. In human volunteers, hypoxic ventilatory drive was shown to be decreased by vecuronium up to a TOFR more than or equal to 0.9.2In another study, the ability to swallow was also found to be impaired when the TOFR was less than 0.9.3Masseter muscle function, assessed by the ability to hold a tongue depressor between one's teeth against resistance, did not return to normal unless TOFR equaled 0.8–0.9.4Therefore, a revisited TOFR threshold more than or equal to 0.90, obtained by force measurement or mechanomyography, was proposed in the late 1990s. With the advent of techniques measuring acceleration, or acceleromyography, a TOFR more than or equal to 1.0 was recommended.5The degree of residual paralysis can be evaluated in different ways: (1) clinical tests requiring the patient's cooperation, which normally can be performed only after emergence; (2) visual or tactile evaluation of responses to TOF or double-burst stimulation (DBS) at the adductor pollicis (qualitative or subjective assessment); and (3) measurement of the TOFR with a device (quantitative or objective measurement).For the conscious and cooperative patient, several clinical tests have been proposed (table 1). Sustained head lift has been studied extensively and was found to correspond to maximum inspiratory pressures ranging from 50 to 53 cm H2O in unanesthetized volunteers partially paralyzed with d -tubocurarine.6However, in volunteers given subparalyzing doses of mivacurium, sustained head lift for 5 s correlated with a measured TOFR ranging from 0.45 to 0.75, lower than the recommended threshold of 0.9.4In patients, the sensitivity of the head-lift test was approximately 10%, whereas specificity was excellent at 87%,7which indicates that residual paralysis is likely in patients unable to maintain a sustained head lift. More recently, the ability to hold a tongue depressor between one's teeth despite the efforts of someone else to pull it out has been proposed as a more sensitive test.4Volunteers given mivacurium were unable to hold the tongue depressor at a mean TOFR less than 0.86, close to the 0.9 threshold. However, the sensitivity of the tongue-depressor test in patients (13%) was not much higher than that of the head-lift test, but its specificity was higher (90%).7When the head-lift or tongue-depressor tests are “passed,” the persistence of a certain degree of residual paralysis cannot be excluded, suggesting that more reliable tests are required. In addition, these clinical tests cannot be performed in the anesthetized patient.Tests involving a stimulator and tactile or visual subjective assessment of the clinical observer have been devised (table 1). Several studies documented that visual or tactile evaluation of the TOF responses correlated poorly with measured TOFR.8–10Even experienced observers are unable to detect TOF fade visually or manually when the actual TOFR exceeds 0.4, which means that residual paralysis may be undetected if TOFR is in the range of 0.4 to 0.9.7This zone of blind paralysis can be reduced somewhat with the DBS mode of stimulation. With DBS, fade can be detected visually or manually up to a measured TOFR of 0.6, still well below the desired 0.9 threshold.9The failure of these subjective methods to detect residual paralysis was confirmed more recently.7,11The specificity of those two tests was good (98–99%), but sensitivity remained poor (11 and 14% for TOF and DBS stimulation, respectively).Therefore, when fade is detected by tactile or visual means, a certain degree of residual paralysis can be expected with a high degree of certainty. In one study, residual paralysis (TOFR 2) are needed.The residual paralysis rate after emergence has been extensively evaluated during the last 30 yr with global frequencies ranging from 5 to more than 85%. This wide variability can be explained by substantial methodologic differences among those studies.Residual paralysis was first documented in the late 1970s, when the threshold for neuromuscular recovery was considered to be a TOFR more than 0.7. It is not surprising that later studies based on a higher TOFR threshold detected a greater frequency of residual paralysis. For example, in a study published in 2003, 526 patients received a single intubating dose (2× the ED95) of atracurium, vecuronium, or rocuronium. At the end of the procedure, which lasted 1–4 h, 16% had a TOFR less than 0.7 but as many as 45% had a TOFR less than 0.9.7In another study involving the same NMBDs (148 patients), the rate of residual paralysis reached 41% based on a TOFR value of 0.7 and 52% when 0.8 was considered as the threshold for recovery.15In patients receiving pancuronium, the frequency of residual paralysis, defined as a TOFR less than 0.7, was less (40%) than if defined as a TOFR less than 0.9 (85%).16With rocuronium, the percentages were lower, but the difference between the threshold of 0.7 (6%) and 0.9 (29%) persisted.16The longer the duration of NMBD action, the higher the frequency of residual paralysis, regardless of the TOFR threshold chosen.17In a nonrandomized study, residual paralysis, defined as a TOFR less than 0.7 in the PACU, was more frequent in patients given pancuronium (36%; 17/47) than in those who had received atracurium (4%; 2/46) or vecuronium (8%; 5/57).18It seems that patients receiving NMBDs by infusion are more likely to have residual paralysis. In 150 patients given atracurium or vecuronium, 100 received the NMBD as repeated boluses and 50 others by continuous infusion.19Neostigmine reversal was administered to 97% of cases. Residual paralysis, defined as a TOFR less than 0.7, was found in 12% of the bolus group patients and in 24% of the infusion group patients on arrival in the PACU. Fifteen minutes later, the problem persisted in 2 and 12%, respectively. These observations suggest that continuous infusion of NMBDs can increase the risk of residual paralysis at emergence.The usefulness of intraoperative neuromuscular monitoring to reduce the frequency of residual paralysis on arrival in the PACU remains a matter of debate. The results of a recent meta-analysis indicated that the use of an intraoperative neuromuscular function monitor was not associated with a decrease of the residual paralysis rate.17However, that study included a number of uncontrolled trials. When analyzing only studies with adequate methodology, based on a Jadad score more than or equal to 3 (i.e. , at least a randomized controlled trial and description of withdrawals), only five articles met these criteria and of them demonstrated a of neuromuscular transmission monitoring to decrease the residual paralysis whereas only one the usefulness of acceleromyography monitoring was evaluated between on two of patients given pancuronium and reversal with monitoring = or = TOFR were measured for after The TOFR was less than 0.7 for patients, whereas only had a TOFR less than this of intraoperative monitoring was also found with In a and study, the degree of residual paralysis after use was between and patients patients in muscle paralysis, defined as a TOFR less than was found in of the and of the Therefore, the problem of residual paralysis can be by neuromuscular monitoring but cannot be it was demonstrated in a randomized study that the of neuromuscular recovery was less with quantitative than with qualitative assessment of reversal of nondepolarizing neuromuscular block seems to be one of the in or to residual paralysis. To no and studies have the of residual paralysis between two reversal Therefore, the of different reversal can only be assessed by of the one study involving patients receiving nondepolarizing NMBDs, received no whereas the patients received but the was not paralysis defined as a TOFR of less than 0.8 was found in of patients who received with in those who did The difference was not evidence of the of reversal agents can be by the results of et al. those obtained by et al. the study, of anesthetized patients paralyzed with atracurium or vecuronium were given or and the frequency of residual paralysis, defined as a TOFR less than 0.7, was the study, patients received vecuronium, and no and residual paralysis, defined with the same criteria, was detected in of consequences of residual paralysis, such as respiratory well but the of the studies were conducted on healthy volunteers in controlled However, a between such residual paralysis and is difficult to because many other can to respiratory complications after a (i.e. , residual of other type of procedure, and duration of the However, the of residual paralysis after emergence have been documented in clinical studies (table of them demonstrated for anesthetized patients in of postoperative and when residual paralysis residual paralysis is an in the postoperative period and a risk for respiratory risk could be decreased by the use of neuromuscular monitoring and administration of reversal et al. yr in a based on of the first after anesthesia that to anesthesia were at least in by postoperative respiratory failure. Residual paralysis was considered to be in six of those (table the same et al. on the causes of to the care unit because of a of anesthesia during a were 53 and the rate was The of of complications in the recovery of these were to ventilatory after reversal of neuromuscular et al. a on by analyzing anesthesia and found that half of the from postanesthesia respiratory More recently, a of risk to anesthesia and considered to be for postoperative and severe detected in the first h, were them, to a residual block was associated with a risk for or This evidence that residual paralysis could be in and severe evidence of associated with residual paralysis during emergence has been demonstrated after pancuronium In a randomized study, the frequency of residual paralysis, defined as a TOFR of less than 0.9, was higher in patients given pancuronium than those administered as in the PACU was found more in patients who had received between residual paralysis (TOFR < 0.9) and postoperative was to a controlled study on patients randomized to pancuronium, vecuronium, or atracurium for or a risk for of postoperative pulmonary defined as on 2 after was as a TOFR less than 0.7 on arrival in the PACU after pancuronium more of those patients with residual paralysis postoperative pulmonary complications when with patients such residual paralysis These that residual paralysis on arrival in the PACU the risk of pulmonary the evidence that undetected residual paralysis during emergence from anesthesia is and may have clinical and of residual paralysis are with neuromuscular monitoring reversal of have shown that to these is relatively For example, a conducted in that 50% of anesthesiologists never use a and only or administered an acetylcholinesterase an NMBD had been Thus, residual paralysis more in actual practice than in studies monitoring and the use of reversal agents were It that it is to to the of residual paralysis, and this a To residual paralysis, must on during are but a number of can be applied depending on the type of and the patient's nondepolarizing NMBD not be given when the can be performed paralysis and the using a such as a airway. However, NMBDs the and of tracheal and lead to less Thus, neuromuscular block is recommended for tracheal even if is not for the duration of the is can be an to nondepolarizing NMBDs but the patient to that have studied the usefulness of a dose nondepolarizing NMBD 2 the ED95) to the of tracheal the of this strategy on the frequency of residual paralysis at the end of the has never been When a high dose (i.e. , 2 the ED95) of nondepolarizing for example, rocuronium, atracurium, and vecuronium, is administered to tracheal must be that an 2 from NMBD to the arrival in the PACU does not an absence of residual the before for neuromuscular monitoring and if muscle paralysis is necessary during a procedure, the of the drug is based on the duration and the patient's of the duration of the procedure, NMBDs, such as pancuronium, be because the residual paralysis rate on arrival in the PACU is particularly mivacurium can be a However, mivacurium is no longer available in the are such as atracurium or to be a for patients with or administration of be to because the residual paralysis rate is higher with the agents lower the dose of the nondepolarizing NMBD and their duration of To decrease the frequency of residual paralysis, anesthesia could be more than However, the frequency of residual paralysis associated with these two anesthesia has never been in a of is because it the duration of the usefulness of intraoperative neuromuscular monitoring to lower the frequency of residual remains a of seems easier and more to use a stimulator to the degree of block during the procedure, to detect residual paralysis during emergence and the for the be on residual paralysis. Two are (1) spontaneous recovery or (2) neuromuscular block with an acetylcholinesterase or selective binding spontaneous recovery is be evidence that neuromuscular function has to a TOFR of more than or equal to 0.9 before tracheal of the clinical tests and qualitative neuromuscular tests can accurately and reliably indicate a return to a TOFR of more than or equal to 0.9. it is easier and more to use objective monitoring, such as an acceleromyography if reversal is to be is not a of residual paralysis can more than or equal to 4 after an intubating dose of rocuronium, vecuronium, or atracurium is administration of a nondepolarizing a neuromuscular monitoring device in to a reversal acetylcholinesterase inhibitors or inhibitors block the which normally at the neuromuscular a more with the nondepolarizing NMBD for to the so that neuromuscular function is However, the of acetylcholinesterase inhibitors is limited, because their maximum is reached when this is reached at doses of or This that acetylcholinesterase inhibitors are not when the block is Therefore, it is to degree of spontaneous recovery has been before the acetylcholinesterase to adequate recovery ≥ 0.9) from a of min, when if only one twitch is to when are it is now recommended to are before (fig. higher doses when block is is not because of the inhibitors also have and of and These can be by such as or However, administration of the is associated with an frequency of can be proposed to block of more at the neuromuscular a that to the NMBD has been This called sugammadex, is a which is a of that and has a somewhat for vecuronium and is an of and It does not to other of NMBDs, such as atracurium, and At the of had been for in but not in of are its of recovery with regardless of block and of In addition, it recovery to TOFR more than or equal to 0.9 when the dose is However, the dose on intensity of the When two are after a TOF stimulation at the ulnar nerve, 2 more at of a posttetanic of at the adductor 4 is as much as can be if is given a minutes after an intubating dose of vecuronium the dose is approximately the same as with data are available for is not against other Because the dose on the of it is recommended to monitor neuromuscular function before and after its administration to the dose and evaluate its of the strategy recovery or measured TOFR more than or equal to 0.9 is before tracheal paralysis is an that can be by an example, a in a single demonstrated that a strategy based on of neuromuscular monitoring and reversal to a decreased residual paralysis rate in the to patients receiving NMBDs were studied during period in = = = and = In quantitative measurement of neuromuscular block was performed in only of and of patients received reversal In corresponding were and respectively. the same the frequency of residual paralysis, defined as a TOFR less than 0.9, decreased from to only that the of simple can a