Neuromuscular Blockade

1. Thilen, Stephan R., Wade A. Weigel, Michael M. Todd, Richard P. Dutton, Cynthia A. Lien, Stuart A. Grant, Joseph W. Szokol, et al. 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): 13–41. doi: https://doi.org/10.1097/ALN.0000000000004379
   • Practice guidelines provide evidence-based recommendations for the management of neuromuscular monitoring and reversal medications during and after general anesthesia. Provides information for type of monitoring and recommended site of monitoring. Recommendation to use quantitative monitoring at the adductor pollicus and confirm TOF recovery >/= 0.9 prior to extubation.
2. Renew JR, Hex K, Johnson P, Lovett P, Pence R. Ease of Application of Various Neuromuscular Devices for Routine Monitoring. Anesth Analg. 2021;132(5):1421-1428. doi:10.1213/ANE.0000000000005213
   • Comparative study to analyze the time to place three different devices: SunStim Plus PNS, acceleromyography-based IntelliVue NMT device, and electromyography-based TetraGraph device. Participants were timed and a Friedman test and pairwise Wilcoxon signed-rank tests were used to evaluate the difference in time to connect different devices. Study concluded that it takes 19 seconds longer to apply quantitative neuromuscular monitor than a PNS. The minimal additional time should not be seen as a barrier to the application of quantitative monitors.
3. Brull SJ, Murphy GS. Residual neuromuscular block: lessons unlearned. Part II: methods to
   reduce the risk of residual weakness. Anesthesia and Analgesia. 2010;111(1):129-140.
   • Review article that examines optimal neuromuscular management strategies used by clinicians to
     reduce the risk of residual paralysis in the early postoperative period. Current evidence demonstrates
     that frequently utilized clinical tests of neuromuscular junction (head lift or hand grip) cannot reliably
     exclude presence of residual paralysis. Clinicians are often unable to detect fade when TOF ratios are
     between .6 and 1.0. Strong evidence that acceleromyography detects small degrees of residual
     blockade (TOF ratios > .6). Complete recovery of neuromuscular function is more likely when
     anticholinesterases are administered early (>15-20 mins before extubation) and at shallower depth of
     block (TOF count of 4). Selective neuromuscular reversal agents may provide clinicians with better tools
     for prevention of postoperative residual weakness.
4. Fortier LP, McKeen D, Turner K, et al. The RECITE Study: A Canadian Prospective, Multicenter
   Study of the Incidence and Severity of Residual Neuromuscular Blockade. Anesthesia and analgesia.
   2015;121(2):366-372.
   
   • A prospective observational study within 8 Canadian hospitals investigating the incidence of residual
     NMB (neuromuscular blockade). Primary objective of the RECITE (Residual Curarization and its
     Incidence of Tracheal Extubation) study was to investigate the incidence of postoperative residual NMB,
     defined as TOF ratio <0.9, at tracheal extubation. Secondary objective was to determine incidence of
     residual NMB upon arrival in PACU. 302 adult patients undergoing open or laparoscopic abdominal
     surgery lasting <4 hours, with ASA 1-3, scheduled for general anesthesia with at least one dose of NMB
     agents for tracheal intubation or maintenance of NMB were enrolled. Data were available for 241
     patients at tracheal extubation, and 207 patients at PACU arrival. Rocuronium was the NMB used in
     99% percent of cases, with remaining participants receiving cisatracurium. Patients intubated with
     succinylcholine received at least 1 dose of nondepolarizing agent, with neostigmine used for reversal.
     The incidence of residual NMB without reversal (TOF ratio < 0.9) was 63.5% at extubation and 56.5%
     upon arrival at PACU. Among patients receiving NMB reversal with neostigmine, residual paralysis was
     present in 64.6% at tracheal extubation and 59.7% at PACU arrival. Exploratory analysis showed use of
     qualitative peripheral neuromuscular monitoring was associated with significantly lower NMB at PACU
     arrival. The incidence of residual NMB both at tracheal extubation and PACU arrival was positively
     associated with significantly higher doses of rocuronium per minute of surgery. This article concluded
     that residual paralysis was common with use of NMB agents, even when monitoring and reversal was
     used. Better use of these agents and monitoring tools is needed.
     3. Bulka CM, Terekhov MA, Martin BJ, Dmochowski RR, Hayes
5. Bulka CM, Terekhov MA, Martin BJ, Dmochowski RR, Hayes RM, Ehrenfeld JM. Nondepolarizing
   Neuromuscular Blocking Agents, Reversal, and Risk of Postoperative Pneumonia. Anesthesiology.
   2016;125(4):647-655.
   
   • An observational study including 13,290 surgical cases involving patients receiving general anesthesia
     between July 2005 and September 2013 were extracted from Vanderbilt University Medical Center’s
     NSQIP database. Of the 13,100 eligible cases, 1,455 surgical cases receiving an intermediate-acting
     depolarizing NMBA were compared to 1,455 propensity score-matched cases not receiving NMBA.
     Additionally, 1,320 cases with NMBA and reversal with neostigmine were compared to 1,320 propensityscore matched cases without reversal. Cases were followed 30 days postoperatively. Two propensityscore-matched analyses was performed. Postoperative pneumonia IRRs (incidence rate ratios) and
     bootstrapped 95% CIs were calculated. Of the 1,455 surgical cases in the cohort receiving NMBA
     intraoperatively, 38 developed pneumonia. Of the surgical cases who did not receive NMBA, 22
     developed postoperative pneumonia. IRR was statistically significant. Of the 1,320 surgical cases who
     received an NMBA intraoperatively without reversal, 149 developed postoperative pneumonia. Of the
     surgical cases who received NMBA with neostigmine, 70 developed pneumonia within 30 days postop.
     Patients not reversed with acetylcholinesterase inhibitor were more than twice as likely to develop
     pneumonia postoperatively compared to those who received reversal with neostigmine. Intraoperative
     use of intermediate nondepolarizing NMBAs is associated with postoperative pneumonia. Among
     patients receiving NMBAs, non-reversal is associated with increased risk of postoperative pneumonia.
6. Lien CA, Kopman AF. Current recommendations for monitoring depth of neuromuscular
   blockade. Current opinion in anaesthesiology. 2014;27(6):616-622.
   
   • Literature review of neuromuscular monitoring and minimum specifications for the purpose of
     improving patient management. Adequate recovery of neuromuscular function has been defined as TOF
     of at least 0.9 measured at the adductor pollicis, monitoring with qualitative nerve stimulator facilitates
     actual TOF ratio. Peripheral nerve stimulators are not routinely used in clinical practice, suggesting
     dosing of NMBAs and anticholinesterases is inappropriate when recovery of neuromuscular function
     upon extubation cannot be guaranteed. Routine use of peripheral nerve stimulators allows rational
     administration of NMBAs.
7. Abad-Gurumeta A, Ripolles-Melchor J, Casans-Frances R, et al. A systematic review of
   sugammadex vs neostigmine for reversal of neuromuscular blockade. Anaesthesia. 2015;70(12):1441-
   1452.
   
   • Systematic review of Sugammadex versus Neostigmine for reversing neuromuscular blockade. 14 RCTs
     included 1,553 participants. Sugammadex reduced all signs of residual postoperative paralysis
     compared to neostigmine, confirming reliable relative risk reduction of at least 50%. Residual paralysis
     after administration of Neostigmine was 8.4 per 100 participants, whereas Sugammades reduced by 4.5
     per 100 to 3.9 per 100. Sugammadex reduced minor postoperative paralysis compared to neostigmine
     with a relative risk of at least 75%. Pooled rate of weakness post neostigmine was 9.4 per 100,
     compared to 4.7 out of 100 with Sugammadex. Sugammadex reduced drug-related side effects
     compared with Neostigmine, while rates of PONV were similar for Sugammadex and Neostigmine.
     Sugammadex reduced the number of patients with clinical signs of postoperative residual paralysis
     caused by Rocuronium as compared to Neostigmine.

Protective Lung Strategies

1. Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with
   lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute
   respiratory distress syndrome. The New England journal of medicine. 2000;342(18):1301-1308.
   
   • A multicenter randomized trial performed in the United States with 861 ICU patients with Acute Lung
     Injury or Acute Respiratory Distress Syndrome. 387 patients received lower tidal volumes 6 mL/kg for
     predicted body weight and 405 patients received traditional tidal volumes of 12mL/kg for predicted
     body weight. Patients were monitored for 28 days for pulmonary and non-pulmonary complications.
     The mortality rate in the group with lower tidal volumes was significantly lower as compared to the
     traditional tidal volume group (31 percent vs. 39.8 percent). In addition, ventilator-free days were
     significantly lower in the group with lower tidal volumes with ventilator days at 8 as compared to those
     in the traditional tidal volume group with ventilator days totaling 10.5. The incidence of barotrauma was
     the same in both groups.
2. Futier E, Constantin JM, Paugam-Burtz C, et al. A trial of intraoperative low-tidal-volume
   ventilation in abdominal surgery. The New England journal of medicine. 2013;369(5):428-437.
   • A multicenter, double-blind, parallel-group trial with 400 patients randomly assigned to receive either
     protective mechanical ventilation or non-protective mechanical ventilation intraoperatively. All patients
     were at least 40 years old and scheduled to undergo elective abdominal surgery lasting 2 or more hours.
     Participating patients were assessed preoperatively for risk of pulmonary complications. Those with a
     score greater than 2 on a 5 point index were included in the trial. Patients in the protective ventilation
     group received tidal volumes of 6-8 mL/kg of predicted body weight, PEEP of 6-8 cm of water, and
     recruitment maneuvers every 30 minutes after tracheal intubation. Patients in the non-protective
     ventilation group received tidal volumes of 10-12 mL/kg of predicted body weight, no PEEP, and no
     recruitment maneuvers. The patients who did not receive protective ventilation had a higher incidence
     of atelectasis (17%) and pneumonia (8%) within 7 days as compared to the protective ventilation group
     with rates of 6.5% of atelectasis and 1.5% experiencing pneumonia. In addition, non-protective
     ventilation strategies resulted in 3% of patients in that group having acute lung injury or ARDS within 7
     days postoperatively compared to only 0.5% in the protective ventilation group. The median length of
     stay for the protective ventilation patients was shorter than the non-protective ventilation group
     (adjusted difference of 2.45 days shorter). There was no difference in ICU admissions or mortality
     between the two groups.
3. Guldner A, Kiss T, Serpa Neto A, et al. Intraoperative protective mechanical ventilation for
   prevention of postoperative pulmonary complications: a comprehensive review of the role of tidal
   volume, positive end-expiratory pressure, and lung recruitment maneuvers. Anesthesiology. 2015;123(3):692-713.
   • A comprehensive review article that explains the pathophysiology associated with postoperative
     pulmonary complications and further compares the literature regarding protective ventilation
     strategies. Guldner et al categorize patients as either having either non-injured or injured lungs
     preoperatively. Both groups are recommended to receive low tidal volumes: 6-8 mL/kg for predicted
     body weight for non-injured lung patients and 6 mL/kg predicted body weight for injured lung patients.
     Low tidal volumes were determined to be the most important protective ventilation strategy. There is
     less evidence for a specific PEEP value or recruitment maneuvers.
4. Hemmes SN, Gama de Abreu M, Pelosi P, Schultz MJ. High versus low positive end-expiratory
   pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre
   randomised controlled trial. Lancet (London, England). 2014;384(9942):495-503.
   • In this randomized controlled trial involving 30 centers across Europe and North and South America,
     patients undergoing open abdominal surgery were divided into two groups. Both groups received low
     tidal volumes (7 mL/kg PBW). However, 445 patients were assigned to a group with high PEEP settings
     (12 cm of water) & recruitment maneuvers while 449 patients were assigned to a second group
     receiving low PEEP (2cm of water) and no recruitment maneuvers. Postoperative pulmonary
     compliations were identified in 174 (39%) of the 445 patients receiving high PEEP and recruitment
     maneuvers as compared to 172 (38%) of the 449 patients in the low PEEP group. The study concluded
     that in patients undergoing open abdominal surgery, the incidence of postoperative pulmonary
     complications was comparable in the first 5 days after surgery. However, patients in the high PEEP group
     experienced hypotension (46%) and required more vasoactive drugs (62%) intraoperatively as compared
     to the low PEEP group (hypotension: 36%; vasoactive drugs: 51%).
5. Sato H, Nakamura K, Baba Y, Terada S, Goto T, Kurahashi K. Low tidal volume ventilation with
   low PEEP during surgery may induce lung inflammation. BMC anesthesiology. 2016;16(1):47.
   • Twenty-eight patients were enrolled in a prospective, randomized controlled study examining the
     effects of low tidal volume ventilation paired with low PEEP for hepatectomy surgery. Half of the
     patients (14) received traditional tidal volumes of 12 mL/kg for predicted body weight and the other half
     of patients (14) received reduced tidal volumes of 6 mL/kg for predicted body weight. Both groups
     received PEEP of 3 cm of water. After six hours of ventilation, interleukin-8 levels were found to be
     elevated in the epithelial lining of the airway for the low tidal volume group. In addition, the P/F ratio
     was higher in the PACU for the traditional tidal volume patients (12mL/kg) when compared to the lower
     tidal volume group. The study concluded that low tidal volume with low PEEP may lead to pulmonary
     inflammation in hepatectomy surgery.
6. Serpa Neto A, Hemmes SN, Barbas CS, et al. Protective versus Conventional Ventilation for
   Surgery: A Systematic Review and Individual Patient Data Meta-analysis. Anesthesiology.
   2015;123(1):66-78.
   • In this meta-analysis of fifteen randomized controlled trials, there was a decreased incidence of
     postoperative pulmonary complications (PPCs) in patients receiving low tidal volumes (≤8mL/kg for
     predicted body weight (PBW)) as compared to patients receiving conventional ventilation (>8 mL/kg
     PBW). The use of PEEP and/or recruitment maneuvers was not included in the definitions for protective
     or conventional ventilation. The reviewers did not determine a difference in PPC incidence with patients
     receiving high or low levels of PEEP when low tidal volumes were applied. However, there was a higher
     incidence of PPCs in patients who received tidal volumes >10 mL/kg PBW and PEEP ≥5 cm of water.