Residual neuromuscular block in vulnerable patients: Obesity, obstructive sleep apnea and postoperative pulmonary complications

Brull, S.J.; Fulesdi, B.
doi:10.1016/j.redare.2019.03.001
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The definition of residual neuromuscular block &#40;rNMB&#41; has evolved over the past 4 decades&#46; In 1973&#44; Ali and Kitz<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">1</span></a> reported that at a train-of-four &#40;TOF&#41; ratio &#40;TOFR&#41; of 0&#46;71&#44; &#8220;the criteria &#91;ability to open eyes&#44; to protrude the tongue&#44; cough and sustain head raising for at least 5<span class="elsevierStyleHsp" style=""></span>sec&#93; were satisfied&#46;&#8221; Thereafter&#44; this threshold &#40;TOFR<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;70&#41; was used to indicate that recovery from neuromuscular block was sufficient to allow tracheal extubation and avoid rNMB&#46; Using this definition&#44; however&#44; despite the introduction of intermediate-duration nondepolarizing neuromuscular blocking agents &#40;NMBAs&#41;&#44; the incidence of rNMB following neostigmine antagonism remained high &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Later clinical and experimental observations clearly demonstrated that the patency of the upper airways during recovery from neuromuscular block can only be maintained at a TOFR of 0&#46;9 or above&#44; a level that is currently considered the threshold of recovery&#46; Despite the plethora of literature that documents the high incidence of hypoxemia&#44; upper airway obstruction&#44; and pneumonia<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">2&#44;3</span></a> in patients with rNMB&#44; the incidence of this easily preventable complication continues to remain astonishingly high &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">One of the patient characteristics that is a potent risk factor for the development of postoperative respiratory complications is obstructive sleep apnea &#40;OSA&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a> a common disorder with an increasing prevalence that is linked to obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">5</span></a> Patients with OSA are prone to developing a series of postoperative adverse events&#59; among them&#44; respiratory complications are the most frequent &#40;overall odds ratio&#44; OR&#44; of 6&#46;88&#41;&#46; In a recent review&#44; an OR of 7&#46;9 was reported for hypoxemia&#44; OR of 4&#46;2 for hypercapnia and OR of 1&#46;37&#8211;1&#46;41 for &#40;aspiration&#41; pneumonia&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">For better understanding of the pathophysiology of these observations&#44; we must recall that OSA patients present airway narrowing at the retropalatal&#44; retroglossal and hypopharyngeal levels even during wakefulness&#59; this worsens during sleep&#44; resulting in a decrease in the critical closing pressure&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">7</span></a> It is widely accepted that there is a difference between the vulnerability of various muscles to neuromuscular blocking agents&#44; the upper airway muscles being more sensitive than peripheral muscles&#44; such as the adductor pollicis&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">8</span></a> While the muscular activity of the genioglossus muscle is quadrupled during inspiration in non-paralyzed individuals&#44; even a shallow &#40;TOFR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;8&#41; neuromuscular block significantly decreases its force&#44; resulting in significant inspiratory flow limitations&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">9</span></a> It also has been shown that during this shallow block&#44; the negative airway pressure generated by the inspiratory movements augments the collapse of the sensitive parts of the airway&#46; In this situation&#44; the opening of the occluded airway depends mainly on the upstream pressure &#40;i&#46;e&#46;&#44; the pressure generated through mask ventilation&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">10</span></a> Thus&#44; patients suffering from OSA are prone to developing a critical airway closure in the postoperative phase&#44; even if a shallow neuromuscular block is present&#46; A recent systematic review concluded that patients with OSA who receive NMBAs may be at higher risk of developing postoperative hypoxemia&#44; residual neuromuscular block and respiratory failure&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">11</span></a> In line with these findings&#44; the American Society of Anesthesiologists &#40;ASA&#41; guidelines recommend that tracheal extubation of OSA patients only be performed when they are awake and when complete reversal of the NMB can verified&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a> Pharmacologic antagonism is particularly important in obese and OSA patients&#46; In morbidly obese patients&#44; administration of sugammadex resulted in shortening of the time needed to reach the fit-for-extubation stage &#40;TOFR<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>90&#37;&#41; and the time to complete recovery of neuromuscular function on arrival at the PACU&#44; compared to patients receiving neostigmine&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">13</span></a> In a randomized study of OSA patients&#44; a shorter time to TOFR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;9 was needed when using sugammadex compared to neostigmine&#46; Additionally&#44; postoperative desaturation occurred in one third of the patients who received neostigmine antagonism&#44; while the sugammadex group experienced a desaturation rate of 8&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">14</span></a> Sugammadex reversal was also associated with better respiratory recovery than neostigmine in morbidly obese patients undergoing elective laparoscopic surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">15</span></a> Patients receiving sugammadex for pharmacologic reversal had significantly higher peak expiratory flow rates at 5&#44; 10 and 20<span class="elsevierStyleHsp" style=""></span>min after reversal than the patients receiving neostigmine and glycopyrrolate&#46; Secondary outcomes included shorter time to a TOF<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;90 and lower mean pain scores for the patients receiving sugammadex&#46; A clue to the potential mechanism for the improved recovery characteristics facilitated by sugammadex has been reported&#46; Electromyographic &#40;EMG&#41; activity of the diaphragm&#44; airway pressure and airway flow were measured continuously after administration of 0&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;kg or rocuronium&#44; and during recovery facilitated by either sugammadex 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg or neostigmine 0&#46;07<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46; Diaphragmatic EMG&#44; tidal volume and PaO2 were higher after sugammadex compared with neostigmine&#44; suggesting that sugammadex may free up more diaphragmatic acetylcholine receptors by encapsulating the free rocuronium molecules than neostigmine&#44; whose indirect mechanism of action &#40;acetylcholinesterase inhibition&#41; is less effective&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">16</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Due to the collapsibility of the upper airway in OSA patients described above&#44; quantitative monitoring of neuromuscular block is crucial&#46; In this particularly vulnerable patient population&#44; initial dosing of NMBAs&#44; supplemental intraoperative doses&#44; maintenance of the optimal depth of intraoperative block&#44; guidance on the timing and dose of pharmacologic agent&#44; and readiness for tracheal extubation &#40;TOFR<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>0&#46;90&#41; can only be assured by using objective &#40;quantitative&#41; means of assessment&#46; Despite abundant evidence that rNMB is a common postoperative complication&#44; a majority of clinicians believe its incidence is less than 1&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">17</span></a> In fact&#44; the most recent&#44; large-scale&#44; prospective multicenter study reported an incidence of rNMB as 64&#46;7&#37;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a>&#59; surprisingly&#44; the incidence of significant postoperative rNMB &#40;defined as TOFR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;6&#41; was reported as 31&#46;0&#37;&#33; As the authors noted&#44; &#8220;qualitative neuromuscular monitoring and clinical judgment often fails to detect rNMB after neostigmine reversal&#44; with potential severe consequences&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a> This preventable complication should be a never-event&#44; because rNMB significantly increases intensive care admissions and healthcare costs&#44; while also increasing the risk of 30-day hospital readmission and prolonging the length of hospital stay&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">19&#44;20</span></a> Second&#44; clinicians continue to rely on clinical tests in order to assess the adequacy of neuromuscular function and readiness for tracheal extubation&#44; despite knowing for decades that clinical tests such as leg-lift&#44; hand-grip strength and 5-second head-lift are not specific for respiratory function&#46; In fact&#44; 92&#37; of volunteers had sustained 5-second head-lift at a TOFR of 0&#46;50&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">21</span></a> and 84&#37; of patients could sustain head-lift at a TOFR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;50&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">22</span></a> The lack of precision and reliability of clinical testing should&#44; however&#44; not surprise us&#59; the sensitivity of clinical tests is very low &#40;0&#46;18&#8211;0&#46;35&#41;&#44; while their positive predictive value is also dismally low&#44; 0&#46;47&#8211;0&#46;52&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">23</span></a> Similarly&#44; clinicians&#8217; reliance on subjective &#40;qualitative&#41; evaluation of information obtained from peripheral nerve stimulators &#40;PNS&#41; leads to erroneous clinical decisions regarding evaluation of neuromuscular recovery&#58; TOF fade is not detectable by subjective means after a TOFR<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;40&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">24</span></a> In fact&#44; when recovery of neuromuscular function is monitored subjectively with PNS of the facial muscles&#44; the incidence of rNMB &#40;TOFR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;90&#41; measured in the postoperative care unit was 52&#37;&#46; As the authors noted&#44; &#8220;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&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">25</span></a> Why&#44; then&#44; despite the wealth of literature that documents the limitations of subjective evaluation and clinical testing&#44; do clinicians insist on maintaining the status quo&#63; A recent world-wide survey of 1629 anesthesiologists from 80 countries completed a 9-question test&#59; the clinicians answered correctly only 57&#37; of the questions&#46; In contrast&#44; their mean confidence in the correctness of their answers was 84&#37;&#44; a figure significantly higher than the clinicians&#8217; accuracy&#46; In fact&#44; 92&#37; of the responding clinicians were overconfident&#46; It is likely that this overconfidence prevents most clinicians from modifying their clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">26</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The aforementioned current clinical practice is unlikely to change as long as clinicians remain overconfident in their abilities and refuse to rely on objective data provided by quantitative monitors&#46; The most likely effective strategy for modifying clinical practice to include objective methods is to teach the new generation of students about the unquestionable benefits of quantitative neuromuscular monitoring&#46; Only then&#44; by changing our thinking&#44; will we be able to solve the problems we created&#33;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Brull SJ&#44; Fulesdi B&#46; Bloqueo neuromuscular residual en pacientes vulnerables&#58; complicaciones pulmonares postoperatorias a causa de obesidad y apnea obstructiva del sue&#241;o&#46; Rev Esp Anestesiol Reanim&#46; 2019&#59;66&#58;237&#8211;240&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Incidence of residual neuromuscular block postoperatively after administration of neostigmine using the recovery threshold of TOFR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;7&#44; and TOFR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>train-of-four ratio&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Incidence of residual neuromuscular postoperatively after administration of neostigmine using the recovery threshold of TOFR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;9&#44; TOFR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>train-of-four ratio&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In the most recent decade&#44; a new reversal agent &#40;antagonist&#41; has been introduced in clinical practice&#46; Sugammadex&#44; a cyclodextrin-based selective binding agent&#44; has the affinity to encapsulate steroidal NMB agents such as rocuronium&#44; vecuronium and pipecuronium&#46; With the use of this reversal agent&#44; the incidence of rNMB gradually decreased&#46; There was hope that routine administration of sugammadex might render neuromuscular monitoring unnecessary&#46; However&#44; clinical studies have shown that empiric administration of the reversal agent without quantitative monitoring guidance to help properly select the appropriate dose of sugammadex still results in a risk of rNMB of roughly 4&#37;&#46;</p>"
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