Incomplete Neuromuscular Recovery Research Articles

This Month in Anesthesiology

This Month in Anesthesiology

Quantitative Neuromuscular Monitoring and Postoperative Outcomes: A Narrative Review.

Over the past five decades, quantitative neuromuscular monitoring devices have been used to examine the incidence of postoperative residual neuromuscular block in international clinical practices, and to determine their role in reducing the risk of residual neuromuscular block and associated adverse clinical outcomes. Several clinical trials and a recent meta-analysis have documented that the intraoperative application of quantitative monitoring significantly reduces the risk of residual neuromuscular blockade in the operating room and postanesthesia care unit. In addition, emerging data show that quantitative monitoring minimizes the risk of adverse clinical events, such as unplanned postoperative reintubations, hypoxemia, and postoperative episodes of airway obstruction associated with incomplete neuromuscular recovery, and may improve postoperative respiratory outcomes. Several international anesthesia societies have recommended that quantitative monitoring be performed whenever a neuromuscular blocking agent is administered. Therefore, a comprehensive review of the literature was performed to determine the potential benefits of quantitative monitoring in the perioperative setting.

Neuromuscular Monitoring in the Perioperative Period.

Neuromuscular monitoring devices were introduced into clinical practice in the 1970s. Qualitative neuromuscular monitors, or peripheral nerve stimulators, provide an electrical stimulus to a motor nerve and the response of corresponding muscle subjectively evaluated. A standard peripheral nerve stimulator provides several patterns of nerve stimulation, including train-of-four (TOF), double-burst, tetanic, and post-tetanic count. Qualitative (and quantitative) monitors are needed to determine onset of neuromuscular blockade, maintain the required depth of muscle relaxation during the surgical procedure, and assess an appropriate dose of reversal agent. However, absence of fade measured with a peripheral nerve stimulator does not exclude residual neuromuscular block; TOF ratios as low as 0.4-0.6 may be present when fade is no longer observed. In addition, the risk of incomplete neuromuscular recovery may be influenced by monitoring site. The adductor pollicis is more sensitive to the effects of neuromuscular blocking agents (compared to the muscles surrounding the eye), and monitoring at this site may more accurately reflect recovery of pharyngeal muscles (the last muscles to recover from the effects of neuromuscular blocking agents, in which dysfunction may persist even at a TOF ratio of 1.0). Quantitative monitors are devices that measure and quantify the degree of muscle weakness and display the results numerically. Several different technologies have been developed, including mechanomyography, electromyography, acceleromyography, kineograph, and phonomyography. Lower doses of anticholinesterases may be used to effectively reverse neuromuscular blockade at TOF ratios of 0.4-0.6; quantitative monitoring is required to determine that this level of neuromuscular recovery has occurred. As clinical tests of muscle strength, peripheral nerve stimulators are unable to determine whether full recovery of neuromuscular function is present at the end of the surgical procedure. The use of quantitative monitors is essential in excluding clinically important muscle weakness (TOF ratios <0.9 to 1.0) at the time of tracheal extubation.

Residual Neuromuscular Blockade and Perioperative Outcomes in the Elderly

The aim of this review is to assess clinical investigations which have examined the use of NMBAs in the elderly, and to recommend neuromuscular management strategies that may optimize recovery in this patient population. A number of clinical studies have assessed the effect of age on NMBA duration. Recovery from cisatracurium has been compared to steroid-based NMBAs (rocuronium and vecuronium) in the elderly. Variability in the duration of action was significantly greater with the steroid-based drugs than cisatracurium. Other studies have demonstrated that the elderly not only demonstrate prolonged recovery from rocuronium and vecuronium neuromuscular blockade, but also significantly more variability in the times to achieve full neuromuscular recovery. Furthermore, reversal of neuromuscular blockade with anticholinesterase agents may require significantly more time in patients older than 70 years of age. Recent clinical trials have demonstrated the elderly are at significantly increased risk for postoperative residual block. Furthermore, older patients not achieving a train-of-four ratio of greater than 0.9 at the time of tracheal extubation are at an increased risk of hypoxemic events, airway obstruction, and unpleasant signs and symptoms of muscle weakness. Reversal of neuromuscular blockade with sugammadex results in a low incidence of residual block; however, the times to achieve a train-of-four ratio of 0.9 are increased in patients over the age of 70. The pharmacodynamics and pharmacokinetic effects of neuromuscular blocking agents are altered in the elderly. When steroid-based muscle relaxants are administered, the time required to achieve full neuromuscular recovery is increased, and significantly more variability in recovery times is observed. Patients over the age of 65 years are at an increased risk of postoperative residual neuromuscular blockade and complications related to incomplete neuromuscular recovery. Increased vigilance in managing dosing, monitoring, and reversal is required in the elderly in order to improve perioperative outcomes.

Residual neuromuscular blockade: management and impact on postoperative pulmonary outcome.

To revise the current literature on concepts for neuromuscular block management. Moreover, consequences of incomplete neuromuscular recovery on patients' postoperative pulmonary outcome are evaluated as well. The incidence of residual paralysis may be as high as 70% and even small degrees of residual paralysis may have clinical consequences. Neostigmine should not be given before return of the fourth response of the train-of-four-stimulation and no more than 40-50 μg/kg should be given. Sugammadex acts more rapidly and more predictably than neostigmine. Finally, there is convincing evidence in the literature that incomplete neuromuscular recovery may lead to a poor postoperative pulmonary outcome. New evidence has emerged about the pathophysiological implications of incomplete neuromuscular recovery. Not only are the pulmonary muscles functionally impaired, but respiratory control is also affected. Residual paralysis endangers the coordination of the pharyngeal muscles and the integrity of the upper airway. However, neuromuscular monitoring and whenever needed pharmacological reversal prevent residual paralysis.

Benefits and risks of sugammadex.

Anesthesiologists daily use a range of drugs, including intravenous anesthetics, neuromuscular-blocking drugs and their antagonists, opioids, and local anesthetics. Antagonists of neuromuscular-blocking drugs are used to reverse the action of neuromuscular-blocking drugs. However, rarely paradoxical muscle weakness [1,2], nausea, vomiting [3], bradyarrhythmias [4,5], and bronchoconstriction [6,7] occur with acetylcholinesterase inhibitors. Sugammadex is a recently introduced antagonist of neuromuscular-blocking drugs. It binds and inactivates neuromuscular-blocking agents, particularly rocuronium and vecuronium. Complex formation between sugammadex and rocuronium or vecuronium results in the rapid reversal of neuromuscular blockade compared to anticholinesterase drugs [8]. In clinical practice and during an unexpectedly difficult airway (cannot intubate, cannot ventilate situation), a rocuronium neuromuscular blockade can be immediately reversed using sugammadex to restore spontaneous ventilation [9]. This is probably the most significant benefit of sugammadex. The ability of sugammadex to reverse rocuronium-induced neuromuscular blockade is not influenced by the choice of anesthetic (e.g., propofol versus sevoflurane) [10,11]. Therefore, when using sugammadex as the antagonist of neuromuscular-blocking drugs, there is a small risk of incomplete neuromuscular recovery or the reoccurrence of neuromuscular blockade following surgery. No dose adjustments are required in older patients [12]. When using antagonists of neuromuscular-blocking drugs, anticholinesterase drugs and anticholinergics (glycopyrrolate and atropine) are coadministered to reduce the cholinergic action of anticholinesterase drugs. In this particular treatment, a side effect is dry mouth. Some patients complain of dry mouth and a gritty taste after general anesthesia and surgery. However, should we select sugammadex as the antagonist of neuromuscular-blocking drugs, we could avoid these problems. Although sugammadex has some benefits, it also has several side effects. Hypersensitivity to sugammadex is the major concern. However, hypersensitivity reactions rarely occur. In patients with known sugammadex hypersensitivity, it is contraindicated. Other reported side effects include coughing, movement of a limb or the body, parosmia (abnormal sense of smell), and elevated urine levels of N-acetyl-glucosaminidase [13]. Theoretically, sugammadex can bind to endogenous and pharmaceutical molecules other than steroidal neuromuscular-blocking drugs, therefore reducing the efficacy of these molecules. When sugammadex has a very high affinity for another molecule, this molecule may displace rocuronium or vecuronium from the complex with sugammadex, resulting in the reoccurrence of neuromuscular blockade [14]. Sugammadex may interact with hormonal contraceptive drugs via unwanted binding, therefore, possibly reducing their clinical efficacy [15]. It should be explained to female patients using hormonal contraceptives that the effectiveness of such drugs could be reduced by the administration of sugammadex. The efficacy and safety of sugammadex in obstetric anesthesia have not been determined. To date, no serious adverse event in the mother or neonate after sugammadex has been reported. Because sugammadex is expensive, this is an important factor that may limit its use as a routine antagonist of neuromuscular-blocking drugs. In this issue of the Korean Journal of Anesthesiology, there are three interesting papers on muscle relaxants [16,17], and sugammadex [18]. The study of sugammadex and its influence on bleeding is quite novel [18]. If you wish to use an antagonist of neuromuscular-blocking drugs, which would you choose between sugammadex and acetylcholinesterase inhibitors? This depends on the decision and experience of the anesthesiologists regarding the benefits and risks of sugammadex, with which they should therefore be well acquainted.

Incidence of postoperative residual neuromuscular blockade in the postanaesthesia care unit

Residual neuromuscular blockade still presents despite the use of intermediate duration muscle relaxants and is a risk factor for postoperative morbidity. To determine the incidence of incomplete postoperative neuromuscular recovery from anaesthesia in a postanaesthesia care unit. Multicentre observational study. Public Portuguese hospitals. Adult patients scheduled for elective surgery requiring general anaesthesia with neuromuscular blocking agents. An independent anaesthesiologist measured neuromuscular transmission by the TOF-Watch SX acceleromyograph. Train-of-four ratios at least 0.9 and less than 0.9 were assessed as complete and incomplete neuromuscular recovery following general anaesthesia, respectively. The study population consisted of 350 patients [134 men and 216 women, mean (SD) age 54.3 (15.9) years]. Ninety-one patients had a train-of-four ratio less than 0.9 on arrival in the postanaesthesia care unit, an incidence of residual neuromuscular blockade of 26% [95% confidence interval (CI) 21 to 31%]. The most frequent neuromuscular blockers were rocuronium (44.2%) and cisatracurium (32%). A neuromuscular block reversal agent was used in 66.6% of the patients (neostigmine in 97%). The incidence of residual neuromuscular blockade in patients receiving reversal agents was 30% (95% CI 25 to 37%). There were no statistically significant differences in the occurrence of residual blockade relating to the neuromuscular blocker used, although higher percentages were observed for cisatracurium (32.4%) and vecuronium (32%) compared with atracurium (23.6%) and rocuronium (20.8%). Incomplete neuromuscular recovery was significantly more frequent among patients who had received a reversal agent (30.5 vs. 17.1%, P = 0.01). Incomplete neuromuscular recovery was more frequent in patients given propofol than in those exposed to sevoflurane (26.2 vs. 14.3%). The incidence of incomplete neuromuscular recovery of 26% confirms that it is relatively frequent in the postoperative period and calls attention to the dimension of this problem in Portugal.

Residual Neuromuscular Block

In this review, we summarize the clinical implications of residual neuromuscular block. Data suggest that residual neuromuscular block is a common complication in the postanesthesia care unit, with approximately 40% of patients exhibiting a train-of-four ratio <0.9. Volunteer studies have demonstrated that small degrees of residual paralysis (train-of-four ratios 0.7-0.9) are associated with impaired pharyngeal function and increased risk of aspiration, weakness of upper airway muscles and airway obstruction, attenuation of the hypoxic ventilatory response (approximately 30%), and unpleasant symptoms of muscle weakness. Clinical studies have also identified adverse postoperative events associated with intraoperative neuromuscular management. Large databased investigations have identified intraoperative use of muscle relaxants and residual neuromuscular block as important risk factors in anesthetic-related morbidity and mortality. Furthermore, observational and randomized clinical trials have demonstrated that incomplete neuromuscular recovery during the early postoperative period may result in acute respiratory events (hypoxemia and airway obstruction), unpleasant symptoms of muscle weakness, longer postanesthesia care unit stays, delays in tracheal extubation, and an increased risk of postoperative pulmonary complications. These recent data suggest that residual neuromuscular block is an important patient safety issue and that neuromuscular management affects postoperative outcomes.

Conventional Neuromuscular Monitoring versus Acceleromyography: It's Not the Monitor but the Anesthetist

We thank Dr. Horowitz for his comments on our study.1We welcome the opportunity to address his criticisms of the methodology used in our investigation and of our conclusions related to the effect of acceleromyography monitoring on residual neuromuscular blockade and adverse postoperative respiratory events.First, we agree with the statement that nuances in neuromuscular management protocols may affect outcomes. Practices related to dosing, monitoring, and reversal of neuromuscular blocking agents may vary widely between institutions. The protocol used in our control group (conventional qualitative train-of-four [TOF] monitoring) was designed to reflect “optimal” neuromuscular management, as defined by Kopman et al. (use of intermediate-acting muscle relaxants, avoidance of total twitch suppression, anticholinesterase reversal of blockade at a TOF count of 3–4).2These techniques, which may reduce the incidence of residual paresis in the postanesthesia care unit, are routinely used at our institution in surgical patients requiring muscle relaxation. Dr. Horowitz suggests that the methodology of neuromuscular monitoring used in the conventional TOF group was flawed, because use of visual evaluation of TOF responses may result in an underestimation of the level of the blockade and an overestimation of neuromuscular recovery. Available evidence does not support this hypothesis. Two studies specifically comparing visual versus tactile assessment of fade concluded that the ability of both techniques to detect fade was comparable at TOF ratios below 0.4 and between 0.4–0.7.3,4The sensitivity in detecting fade was poor with both methods at all TOF ratios > 0.4, and no statistically or clinically significant differences were observed when either visual or tactile assessments were evaluated.3,4Therefore, we do not believe that using tactile instead of visual evaluations of TOF responses would have influenced our findings in the conventional TOF group. In addition, there are no clinical studies demonstrating that the use of tactile assessments of TOF responses results in a reduced incidence of postoperative residual blockade when compared to visual evaluations.Second, Dr. Horowitz questions our use of interoperative acceleromyography monitoring in our study group. We agree that quantitative neuromuscular monitoring does not provide any additional information over standard peripheral nerve monitoring during moderate levels of neuromuscular blockade (TOF count of 2–3) required for surgical relaxation. As described in our article, the value of acceleromyography monitoring is primarily during neuromuscular recovery. Our data suggests that acceleromyography monitoring allows for more rational and precise neuromuscular management during the last 45–60 minutes of the anesthetic.Third, Dr. Horowitz states that we “did not follow common practices of neuromuscular monitoring and management of extubation when using a conventional monitor.” Dr. Horowitz does not define what these “common practices” are. Current evidence suggests that “common practices of neuromuscular monitoring” are not evidence-based, and techniques proven to reduce the incidence of residual neuromuscular blockade are infrequently applied by clinicians. Surveys from Germany, Denmark, France, and Great Britain all indicate that quantitative and qualitative monitoring is rarely used in daily clinical practice.5–7In addition, knowledge about appropriate neuromuscular and clinical criteria required to exclude residual paresis before tracheal extubation is lacking.5–7Although we did not follow “common practices of neuromuscular management” (which would have increased the incidence of residual neuromuscular blockade in the conventional TOF group), we believe that our neuromuscular management protocol represented the best available evidence. In fact, the two previous randomized acceleromyography trials compared a group of patients monitored with acceleromyography with a control group receiving no neuromuscular monitoring (the more “common clinical practice of neuromuscular monitoring” referred to by Dr. Horowitz).8,9Of interest, the incidence of residual paresis was significantly reduced by acceleromyography monitoring in all three randomized trials. Furthermore, neuromuscular blockade was reversed at a mean visual TOF count of 4 in both groups, which represents good “evidence-based” practice.Methods proven to reduce the incidence of postoperative residual blockade (use of intermediate-acting neuromuscular blocking agents, avoidance of total twitch suppression, anticholinesterase reversal of blockade at a TOF count of 3–4) should be adopted by clinicians. However, current data does not support the belief expressed by Dr. Horowitz that use of tactile assessment of TOF responses is superior to visual evaluation in reducing the risk of residual neuromuscular blockade and adverse postoperative outcomes. At the present time, “evidence-based standards for conventional monitoring” as described by Dr. Horowitz do not exist. Such guidelines would likely result in increased routine use of neuromuscular monitoring and anticholinesterase agents, and reduced complications related to incomplete neuromuscular recovery in the postoperative period.*Evanston Northwestern Healthcare, Evanston, Illinois. dgmurphy2@yahoo.com

Residual Neuromuscular Blockade and Critical Respiratory Events in the Postanesthesia Care Unit

Incomplete recovery of neuromuscular function may impair pulmonary and upper airway function and contribute to adverse respiratory events in the postanesthesia care unit (PACU). The aim of this investigation was to assess and quantify the severity of neuromuscular blockade in patients with signs or symptoms of critical respiratory events (CREs) in the PACU. We collected data over a 1-yr period. PACU nurses identified patients with evidence of a predefined CRE during the first 15 min of PACU admission. Train-of-four (TOF) ratios were immediately quantified in these patients using acceleromyography (cases). TOF data were also collected in a control group that consisted of patients undergoing a general anesthetic during the same period who were matched with the cases by age, sex, and surgical procedure. A total of 7459 patients received a general anesthetic during the 1-yr period, of whom 61 developed a CRE. Forty-two of these cases were matched with controls and constituted the study group for statistical analysis. The most common CREs among matched cases were severe hypoxemia (22 of 42 patients; 52.4%) and upper airway obstruction (15 of 42 patients; 35.7%). There were no significant differences between the cases and matched controls in any measured preoperative or intraoperative variables. Mean (+/-sd) TOF ratios were 0.62 (+/-0.20) in the cases, with 73.8% of the cases having TOF ratios <0.70. In contrast, TOF values in the controls were 0.98 (+/-0.07) (a difference of -0.36 with a 95% confidence interval of -0.43 to -0.30, P < 0.0001), and no control patients were observed to have TOF values <0.70 (the 95% confidence interval of the difference was 59%-85%, P < 0.0001). A high incidence of severe residual blockade was observed in patients with CREs, which was absent in control patients without CREs. These findings suggest that incomplete neuromuscular recovery is an important contributing factor in the development of adverse respiratory events in the PACU.

Acceleromyography vs. electromyography: an ipsilateral comparison of the indirectly evoked neuromuscular response to train‐of‐four stimulation

There is a considerable body of evidence which suggests that data obtained using acceleromyography (AMG) cannot be used interchangeably with observations obtained by mechanomyographic (MMG) or electromyograhic (EMG) methods. All previous such studies evaluated the responses from contralateral limbs. This investigation was undertaken to determine if these previously described differences were in part a function of observing the responses from opposing limbs. We compared the ipsilateral EMG and AMG response to an ED(95) bolus of atracurium in 50 subjects. In half of the individuals the thumb was free to move freely; in half, a small elastic preload was applied to the thumb. Train-of-four (TOF) recovery was followed until a TOF ratio >0.90 was recorded by both monitors. Acceleromyography vs. EMG differences and the resultant 95% confidence limits for twitch height (T1) and the TOF ratio were determined. When the AMG TOF value had recovered to a value of 0.72 +/- 0.03; the simultaneously evoked EMG value averaged only 0.59 +/- 0.08. This difference was statistically significant (P < 0.001). Although the mean difference AMG vs. EMG was little more than 0.10, differences in an individual might be twice that amount. When the AMG TOF value had recovered to 0.90, the simultaneously evoked EMG value averaged 0.85. Again the 95% confidence limits for individual observations was very wide. With EMG, once the TOF ratio returns to a value of 0.70, T1 has returned to 95% of control. In contrast with AMG, return of T1 -95% of control requires a TOF ratio of almost 0.90. Addition of an elastic preload to the thumb decreased control TOF variability without effecting the relationship between twitch height and the TOF ratio. Acceleromyographic TOF values tend to overestimate the extent of EMG recovery. Acceleromyographic TOF values <0.90 are indicative of incomplete neuromuscular recovery.