Perioperative residual paralysis

Hello again and welcome to the second installment in the podcast series on perioperative safety. My name is Dr Robert Bilkovski and in this episode, we will review the topic of postoperative residual paralysis. Specifically, we will get a better understanding of the frequency of occurrence, the potential patient harms that may occur and the views coming from anesthesiology associations on this topic. 

The use of non-depolarizing paralytic agents during general anesthesia have been commonplace for decades and the risk for residual paralysis affecting patient safety in the post-operative setting has been reported dating back to the 1970s where nearly half of the patients arriving to the PACU had residual paralysis.^[1] Neuromuscular blockade is frequently used during anesthesia to support endotracheal intubation, optimize surgical conditions, and assist with mechanical ventilation in patients who have reduced lung compliance. In addition, the depth of paralysis should be closely monitored during the entire duration of surgery using train-of-four stimulation. Train of four monitoring is the most common method used to monitoring the extent of neuromuscular blockade.^[2] The train-of-four ratio is calculated by dividing the amplitude of the fourth twitch to the amplitude of the first twitch and monitoring technology exists to support the clinician in making this assessment. If the ratio is <0.9, it indicates that residual paralysis remains and there is a continued need to use a reversal agent. Other methodology used all focus on differing  patterns of stimulation patterns to assess residual paralysis which includes double-burst stimulation, post-tetanic count and tetanic stimulation.^[3]All leverage a similar method of stimulation, with the same pulse waveform and pulse duration. What differs is the frequency of impulses and means of evaluation between each stimulation. Double-burst stimulation delivers two bursts separated by 750 milliseconds, where the muscle contractions following the second burst is less than the first and allows clinicians to evaluate the fade of contraction between the two bursts. This method is more sensitive for tactile evaluation of a residual blockage and has been shown to be comparable to train of four assessments. Similarly with train of four, it has limited utility to assess deep blocks but useful during the onset of paralysis and at the time of recovery. Post-tetanic count (or PTC) is more useful during deep blocks where train of four is considered to be insensitive and supports bringing a patient out of very deep paralysis. The PTC delivers a stimulus (of 50 Hz for 5 sec) and is followed 3 seconds later by a single supramaximal stimuli and delivered once every second. The number of twitches recognized is inversely proportional to the degree of block, and is known as the post tetanic twitch count. Lastly, tetanic stimulation involves high frequency stimulation that is usually applied for 5 seconds. What is observed is for the presence or absence of a muscle contraction fade effect; where the absence of fading suggests acceptable levels of paralysis have been attained. paralysis is comparable to a train of for of approximately 0.85. Compared to DBS or train of four for use during recovery, the specificity has been reported to be low.

To further complicate matters, there are multiple device types that can be used for quantitative assessment for train of four and include acceler-myography, kine-myography and electro-myography, to name a few.^[4] Accelero-myography (or AMG) has been the most widely studied technology and uses a transducer placed on the muscle of interest to measure the response to an electrical stimuli when applied to that muscle; the muscle most commonly stimulated is the thumb. Kinemoyography (or KMG) is closely related to AMG and uses a special type of sensor placed in the groove between the thumb and index finger and senses bending of the thumb in response to electrical stimulation. Lastly, electro-myography (or EMG) is considered by experts to be the new gold standard which measures combined muscle action potentials rather than movement, in response to electrical stimuli. These amplitude of these action potentials is directly proportional to the number of muscle fibers activated, and thus the force of contraction. One limitation is that other forms of electrical stimuli during surgery, like electrocautery, may interfere with the measurements.

Literature shows that residual paralysis in the postoperative period is relatively common, where it has been reported to be as high as 40%.^[5][6]Unfortunately, clinicians frequently rely on clinical signs that include but not limited to head lift, hand grip and negative inspiratory force to determine if residual paralysis exists. These clinical signs are insensitive indicators in those patients coming out of general anesthesia and remain reliable only in awake patients.  The risk for residual paralysis while the patient remains in the post-anesthesia care unit includes:^[7]

1. the need for tracheal reintubation
2. impaired oxygenation and ventilation
3. impaired pulmonary function such as reduced forced vital capacity
4. increased risk for aspiration and pneumonia
5. pharyngeal dysfunction, and lastly may culminate in
6. a delayed discharge from the PACU

Re-intubation in and of itself is a notable risk to the patient and also bears an economic cost to the hospital system. In a publication in the British Journal of Anesthesia, re-intubation was shown to increase the risk for cardiac and respiratory complications, extended the length of stay in the PACU and the ICU on hospital, increased the duration of mechanical ventilation and ultimately an increased risk for death.^[8]

Some additional studies add further details on the frequency and importance of monitoring residual paralysis:

1. The RECITE-US study showed that in a 255-patient study in those undergoing abdominal surgery, almost 65% has a train of four ratio less than 0.9 at the time of extubation. This is despite the fact that the patients received reversing agents for neuromuscular blockade and qualitative peripheral nerve stimulation was monitored.^[9]
2. A large multi-center study from Spain reported that the patients with TOF ratios < 0.9 in the PACU were at an increased risk for postoperative adverse respiratory events, where the odd ratio was 2.57 and had a higher incidence of re-intubation.^[10]
3. A retrospective cohort study, which looked at the impact of postoperative residual paralysis on ICU admissions rates, hospital costs, and hospital length of stay, reported that patients with TOF ratios < 0.9 had a three-times higher risk of ICU admission than those with TOF ratios ≥ 0.9.^[11]and lastly, 
4. Several studies showed that failure to administer a reversal agent in the operating room was associated with increased complications such as post-operative pneumonia, failure to wean, re-intubation and unplanned ICU admissions.^[12][13][14]

The American Society of Anesthesia issued a recommendation where quantitative neuromuscular monitoring should be used whenever neuromuscular blocking agents are being utilized, throughout all phases of anesthesia.^[15] It is important to highlight that a quantitative monitor is the ideal for qualitative monitors lack the needed fidelity to determine sufficient reversal from neuromuscular blockade.^[16]  Furthermore, train of four determinations with qualitative monitors are suitable up to the 0.4 level which is lower than the 0.9 threshold recommended by the ASA in this guideline. The Anesthesia Patient Safety Foundation has issued a position and state that residual neuromuscular blockade in the postoperative period is a patient safety hazard that could be addressed partially by better and consistent use of our qualitative standard train-of-four nerve stimulator monitors, but will ultimately require quantitative (or objective TOF) monitoring along with traditional subjective observations to eliminate this problem completely. The need for intraoperative train of four monitoring is quite clear and further emphasis on routine use can drive further improvements in patient safety. 

Adding an additional layer of complexity is the use of sugammadex, which is a reversal agent of neuromuscular blocking agents that has grown in clinical use over the past decade or two and is highlighted by a faster recovery time and improved safety profile than legacy reversal agents.^[17] However, the risk of incomplete reversal remains an important clinical problem and use of train-of-four  in combination has been show to reduced as compared to use of sugammadex without quantitative monitoring.^[18]

This ends this podcast on the topic of perioperative residual paralysis and you were able to take away the fact that this problem remains common and is associated with increased risk for complications that increase the patient’s risk for a poor post-operative outcome. Thank you for listening and be sure to visit again on other topics pertaining perioperative safety in coming podcasts. Thank you.

References:

[1]     Jørgen Viby-Mogensen, Bent Chraemmer Jørgensen, Helle Ørding; Residual Curarization in the Recovery Room. Anesthesiology 1979; 50:539–541.

[2]     Cook, D. and Simons, D.J., 2021. Neuromuscular blockade. In StatPearls [Internet]. StatPearls Publishing.

[3]     Fuchs-Buder, T., Schreiber, J.-.-U. and Meistelman, C. (2009), Monitoring neuromuscular block: an update. Anaesthesia, 64: 82-89.

[4]     Renew, J.R., Advancements in Quantitative Neuromuscular Monitoring. Perioperative Hypotension, p.117.

[5]     Todd MM, Hindman BJ, King BJ. The implementation of quantitative electromyographic neuromuscular monitoring in an academic anesthesia department. Anesth Analg 2014;119:323–331.

[6]     Checketts MR, Alladi R, Ferguson K, et al. Recommendations for standards of monitoring during anaesthesia and recovery 2015: Association of Anaesthetists of Great Britain and Ireland. Anaesthesia 2015.

[7]     Stoelting, R.K., 2016. Monitoring of neuromuscular blockade: what would you expect if you were the patient. APSF Newslett, 30(3), pp.45-47.

[8]     Rujirojindakul, P., Geater, A.F., McNeil, E.B., Vasinanukorn, P., Prathep, S., Asim, W. and Naklongdee, J., 2012. Risk factors for reintubation in the post-anaesthetic care unit: a case–control study. British journal of Anesthesia, 109(4), pp.636-642.

[9]     Saager L, Maiese EM, Bash LD, et al. Incidence, risk factors, and consequences of residual neuromuscular block in the United States: The prospective, observational, multicenter RECITE-US study. J Clin Anesth. 2019;55:33–41.

[10]   Errando CL, Garutti I, Mazzinari G, et al. Residual neuromuscular blockade in the postanesthesia care unit: observational cross-sectional study of a multicenter cohort. Minerva Anestesiol. 2016;82:1267–1277.

[11]   Grabitz SD, Rajaratnam N, Chhagani K, et al. The effects of postoperative residual neuromuscular blockade on hospital costs and intensive care unit admission: a population-based cohort study. Anesth Analg. 2019;128:1129–1136

[12]   Bulka CM, Terekhov MA, Martin BJ, et al. Nondepolarizing neuromuscular blocking agents, reversal, and risk of postoperative pneumonia. Anesthesiology. 2016;125:647–55.

[13]   Bronsert MR, Henderson WG, Monk TG, et al. Intermediate-acting nondepolarizing neuromuscular blocking agents and risk of postoperative 30-day morbidity and mortality, and long-term survival. Anesth Analg. 2017;124:1476–1483.

[14]   Belcher AW, Leung S, Cohen B, et al. Incidence of complications in the post-anesthesia care unit and associated healthcare utilization in patients undergoing non-cardiac surgery requiring neuromuscular blockade 2005–2013: a single center study. J Clin Anesth. 2017;43:33–38.  15

[15]   Klein AA, Meek T, Allcock E, Cook TM, Mincher N, Morris C, Nimmo AF, Pandit JJ, Pawa A, Rodney G, Sheraton T. Recommendations for standards of monitoring during anaesthesia and recovery 2021: Guideline from the Association of Anaesthetists. Anaesthesia. 2021 Sep;76(9):1212-23.

[16]   Brull SJ, Murphy GS. Residual neuromuscular block: lessons unlearned. Part II: methods to reduce the risk of residual weakness. Anesth Analg. 2010 Jul;111(1):129-40.

[17]   Mirakhur, R.K., 2009. Sugammadex in clinical practice. Anaesthesia, 64, pp.45-54.

[18]   Thilen, S.R., Weigel, W.A., Todd, M.M., Dutton, R.P., Lien, C.A., Grant, S.A., Szokol, J.W., Eriksson, L.I., Yaster, M., Grant, M.D. and Agarkar, M., 2023. 2023 American Society of Anesthesiologists practice guidelines for monitoring and antagonism of neuromuscular blockade: a report by the American Society of Anesthesiologists task force on neuromuscular blockade. Anesthesiology, 138(1), pp.13-41.