Sugammadex versus Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications (STRONGER): A Multicenter Matched Cohort Analysis

Sachin Kheterpal, Michelle T Vaughn, Timur Z Dubovoy, Nirav J Shah, Lori D Bash, Douglas A Colquhoun, Amy M Shanks, Michael R Mathis, Roy G Soto, Amit Bardia, Karsten Bartels, Patrick J McCormick, Robert B Schonberger, Leif Saager, Sachin Kheterpal, Michelle T Vaughn, Timur Z Dubovoy, Nirav J Shah, Lori D Bash, Douglas A Colquhoun, Amy M Shanks, Michael R Mathis, Roy G Soto, Amit Bardia, Karsten Bartels, Patrick J McCormick, Robert B Schonberger, Leif Saager

Abstract

Background: Five percent of adult patients undergoing noncardiac inpatient surgery experience a major pulmonary complication. The authors hypothesized that the choice of neuromuscular blockade reversal (neostigmine vs. sugammadex) may be associated with a lower incidence of major pulmonary complications.

Methods: Twelve U.S. Multicenter Perioperative Outcomes Group hospitals were included in a multicenter observational matched-cohort study of surgical cases between January 2014 and August 2018. Adult patients undergoing elective inpatient noncardiac surgical procedures with general anesthesia and endotracheal intubation receiving a nondepolarizing neuromuscular blockade agent and reversal were included. Exact matching criteria included institution, sex, age, comorbidities, obesity, surgical procedure type, and neuromuscular blockade agent (rocuronium vs. vecuronium). Other preoperative and intraoperative factors were compared and adjusted in the case of residual imbalance. The composite primary outcome was major postoperative pulmonary complications, defined as pneumonia, respiratory failure, or other pulmonary complications (including pneumonitis; pulmonary congestion; iatrogenic pulmonary embolism, infarction, or pneumothorax). Secondary outcomes focused on the components of pneumonia and respiratory failure.

Results: Of 30,026 patients receiving sugammadex, 22,856 were matched to 22,856 patients receiving neostigmine. Out of 45,712 patients studied, 1,892 (4.1%) were diagnosed with the composite primary outcome (3.5% sugammadex vs. 4.8% neostigmine). A total of 796 (1.7%) patients had pneumonia (1.3% vs. 2.2%), and 582 (1.3%) respiratory failure (0.8% vs. 1.7%). In multivariable analysis, sugammadex administration was associated with a 30% reduced risk of pulmonary complications (adjusted odds ratio, 0.70; 95% CI, 0.63 to 0.77), 47% reduced risk of pneumonia (adjusted odds ratio, 0.53; 95% CI, 0.44 to 0.62), and 55% reduced risk of respiratory failure (adjusted odds ratio, 0.45; 95% CI, 0.37 to 0.56), compared to neostigmine.

Conclusions: Among a generalizable cohort of adult patients undergoing inpatient surgery at U.S. hospitals, the use of sugammadex was associated with a clinically and statistically significant lower incidence of major pulmonary complications.

Figures

Figure 1:
Figure 1:
Major pulmonary complication event rates (unadjusted) in matched cohort of patients undergoing noncardiac inpatient surgery Patients receiving sugammadex were matched to patients receiving neostigmine across twelve hospitals using exact match criteria of institution, sex, age, comorbidities, obesity, surgical procedure type, and neuromuscular blockade agent. The composite pulmonary complication primary outcome included pneumonia, respiratory failure, and other major complications.
Figure 2:
Figure 2:
Unadjusted and adjusted association of sugammadex versus neostigmine administration with major pulmonary complications after inpatient noncardiac surgery In a matched cohort of patients, the association of sugammadex with composite and individual major pulmonary complications was assessed using multivariable conditional logistic regression adjusting for covariates with residual absolute standardized difference > 0.10. The composite pulmonary complication primary outcome included pneumonia, respiratory failure, and other major complications.

References

    1. Kirmeier E, Eriksson LI, Lewald H, Jonsson Fagerlund M, Hoeft A, Hollmann M, Meistelman C, Hunter JM, Ulm K, Blobner M, POPULAR Contributors: Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study. Lancet Respir Med 2019; 7:129–40
    1. Dimick JB, Chen SL, Taheri PA, Henderson WG, Khuri SF, Campbell DA Jr: Hospital costs associated with surgical complications: a report from the private-sector National Surgical Quality Improvement Program. J Am Coll Surg 2004; 199:531–7
    1. Freundlich RE, Maile MD, Sferra JJ, Jewell ES, Kheterpal S, Engoren M: Complications Associated With Mortality in the National Surgical Quality Improvement Program Database. Anesthesia & Analgesia 2018; 127:55–62
    1. Meara JG, Leather AJM, Hagander L, Alkire BC, Alonso N, Ameh EA, Bickler SW, Conteh L, Dare AJ, Davies J, Mérisier ED, El-Halabi S, Farmer PE, Gawande A, Gillies R, Greenberg SLM, Grimes CE, Gruen RL, Ismail EA, Kamara TB, Lavy C, Lundeg G, Mkandawire NC, Raykar NP, Riesel JN, Rodas E, Rose J, Roy N, Shrime MG, Sullivan R, Verguet S; Watters D; Weiser TG; Wilson IH; Yamey G; Yip W: Global Surgery 2030: evidence and solutions for achieving health, welfare, and economic development. Int J Obstet Anesth 2016; 25:75–8
    1. Nepogodiev D, Martin J, Biccard B, Makupe A, Bhangu A: Global burden of postoperative death. Lancet 2019; 393:401.
    1. Grosse-Sundrup M, Henneman JP, Sandberg WS, Bateman BT, Uribe JV, Nguyen NT, Ehrenfeld JM, Martinez EA, Kurth T, Eikermann M: Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study. BMJ 2012; 345:e6329.
    1. Lundstrøm LH, Duez CH, Nørskov AK, Rosenstock CV, Thomsen JL, Møller AM, Strande S, Wetterslev J: Avoidance versus use of neuromuscular blocking agents for improving conditions during tracheal intubation or direct laryngoscopy in adults and adolescents. Cochrane Database Syst Rev 2017; 5:CD009237.
    1. Murphy GS: Neuromuscular Monitoring in the Perioperative Period. Anesth Analg 2018; 126:464–8
    1. Bruintjes MH, van Helden EV, Braat AE, Dahan A, Scheffer GJ, van Laarhoven CJ, Warlé MC: Deep neuromuscular block to optimize surgical space conditions during laparoscopic surgery: a systematic review and meta-analysis. Br J Anaesth 2017; 118:834–42
    1. Murphy G, De Boer HD, Miller RD: Miller’s Anesthesia, Ninth Edition; Chapter 28: Reversal (Antagonism) of Neuromuscular Blockade. Edited by Gropper MA, Miller RD, Cohen NH, Eriksson LI, Fleisher LA, Leslie K, Wiener-Kronish JP. Elsevier Saunders, 2019, pages 832–864
    1. Hristovska A-M, Duch P, Allingstrup M, Afshari A: Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults. Cochrane Database Syst Rev 2017; 8:CD012763.
    1. Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear TD, Deshur MA, Benson J, Newmark RL, Maher CE: Neostigmine Administration after Spontaneous Recovery to a Train-of-Four Ratio of 0.9 to 1.0: A Randomized Controlled Trial of the Effect on Neuromuscular and Clinical Recovery. Anesthesiology 2018; 128:27–37
    1. Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear T, Vender JS, Gray J, Landry E: Postoperative residual neuromuscular blockade is associated with impaired clinical recovery. Anesth Analg 2013; 117:133–41
    1. Fortier L-P, McKeen D, Turner K, de Médicis É, Warriner B, Jones PM, Chaput A, Pouliot J-F, Galarneau A: The RECITE Study: A Canadian Prospective, Multicenter Study of the Incidence and Severity of Residual Neuromuscular Blockade. Anesth Analg 2015; 121:366–72
    1. Saager L, Maiese EM, Bash LD, Meyer TA, Minkowitz H, Groudine S, Philip BK, Tanaka P, Gan TJ, Rodriguez-Blanco Y, Soto R, Heisel O: 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
    1. Bulka CM, Terekhov MA, Martin BJ, Dmochowski RR, Hayes RM, Ehrenfeld JM: Nondepolarizing Neuromuscular Blocking Agents, Reversal, and Risk of Postoperative Pneumonia. Anesthesiology 2016; 125:647–55
    1. Krause M, McWilliams SK, Bullard KJ, Mayes LM, Jameson LC, Mikulich-Gilbertson SK, Fernandez-Bustamante A, Bartels K: Neostigmine Versus Sugammadex for Reversal of Neuromuscular Blockade and Effects on Reintubation for Respiratory Failure or Newly Initiated Noninvasive Ventilation: An Interrupted Time Series Design. Anesth Analg 2019. doi:10.1213/ANE.0000000000004505 (Published ahead of print)
    1. Timur D, Kheterpal S, Shah N, Saager L, Housey S: E163. Real World Utilization Patterns of Perioperative Neuromuscular Blockade Reversal in the United States: A Retrospective Observational Study from the Multicenter Perioperative Outcomes Group, International Anesthesia Research Society Abstracts Poster Session; Montreal, Canada, May 20, 2019
    1. Freundlich RE, Kheterpal S: Perioperative effectiveness research using large databases. Best Pract Res Clin Anaesthesiol 2011; 25:489–98
    1. Berman MF, Iyer N, Freudzon L, Wang S, Freundlich RE, Housey M, Kheterpal S, Multicenter Perioperative Outcomes Group (MPOG) Perioperative Clinical Research Committee: Alarm Limits for Intraoperative Drug Infusions: A Report From the Multicenter Perioperative Outcomes Group. Anesth Analg 2017; 125:1203–11
    1. Kheterpal S, Healy D, Aziz MF, Shanks AM, Freundlich RE, Linton F, Martin LD, Linton J, Epps JL, Fernandez-Bustamante A, Others: Incidence, predictors, and outcome of difficult mask ventilation combined with difficult laryngoscopy: A report from the multicenter perioperative outcomes group. Anesthesiology 2013; 119:1360–9
    1. Sun E, Mello MM, Rishel CA, Vaughn MT, Kheterpal S, Saager L, Fleisher LA, Damrose EJ, Kadry B, Jena AB, for the Multicenter Perioperative Outcomes Group (MPOG): Association of Overlapping Surgery With Perioperative Outcomes. JAMA 2019; 321:762.
    1. Lee LO, Bateman BT, Kheterpal S, Klumpner TT, Housey M, Aziz MF, Hand KW, MacEachern M, Goodier CG, Bernstein J, Bauer ME: Risk of Epidural Hematoma after Neuraxial Techniques in Thrombocytopenic ParturientsA Report from the Multicenter Perioperative Outcomes Group. Anesthesiology 2017; 126:1053–63
    1. O’Reilly-Shah VN, Wolf FA, Jabaley CS, Lynde GC: Using a worldwide in-app survey to explore sugammadex usage patterns: a prospective observational study. Br J Anaesth 2017; 119:333–5
    1. Hurwitz EE, Simon M, Vinta SR, Zehm CF, Shabot SM, Minhajuddin A, Abouleish AE: Adding Examples to the ASA-Physical Status Classification Improves Correct Assignment to Patients. Anesthesiology 2017; 126:614–22
    1. Jammer I, Wickboldt N, Sander M, Smith A, Schultz MJ, Pelosi P, Leva B, Rhodes A, Hoeft A, Walder B, Chew MS, Pearse RM, European Society of Anaesthesiology (ESA) and the European Society of Intensive Care Medicine (ESICM), European Society of Anaesthesiology, European Society of Intensive Care Medicine: Standards for definitions and use of outcome measures for clinical effectiveness research in perioperative medicine: European Perioperative Clinical Outcome (EPCO) definitions: a statement from the ESA-ESICM joint taskforce on perioperative outcome measures. Eur J Anaesthesiol 2015; 32:88–105
    1. Abbott TEF, Fowler AJ, Pelosi P, Gama de Abreu M, Møller AM, Canet J, Creagh-Brown B, Mythen M, Gin T, Lalu MM, Futier E, Grocott MP, Schultz MJ, Pearse RM, StEP-COMPAC Group: A systematic review and consensus definitions for standardised end-points in perioperative medicine: pulmonary complications. Br J Anaesth 2018; 120:1066–79
    1. Ladha K, Vidal Melo MF, McLean DJ, Wanderer JP, Grabitz SD, Kurth T, Eikermann M: Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study. BMJ 2015; 351:h3646.
    1. Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi J-C, Saunders LD, Beck CA, Feasby TE, Ghali WA: Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 2005; 43:1130–9
    1. Goodman MS, Li Y: Nonparametric Diagnostic Test for Conditional Logistic Regression. J Biom Biostat 2012; 3
    1. Steyerberg EW, Vickers AJ, Cook NR, Gerds T, Gonen M, Obuchowski N, Pencina MJ, Kattan MW: Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology 2010; 21:128–38
    1. Freundlich RE, Duggal NM, Housey M, Tremper TT, Engoren MC, Kheterpal S: Intraoperative medications associated with hemodynamically significant anaphylaxis. J Clin Anesth 2016; 35:415–23
    1. Saager L, Turan A, Egan C, Mascha EJ, Kurz A, Bauer M, Besson H, Sessler DI, Hesler BD: Incidence of Intraoperative Hypersensitivity Reactions: A Registry Analysis. Anesthesiology 2015; 122:551–9
    1. Haneuse S, VanderWeele TJ, Arterburn D: Using the E-Value to Assess the Potential Effect of Unmeasured Confounding in Observational Studies. JAMA 2019; 321:602–3
    1. Lawrence VA, Cornell JE, Smetana GW, American College of Physicians: Strategies to reduce postoperative pulmonary complications after noncardiothoracic surgery: systematic review for the American College of Physicians. Ann Intern Med 2006; 144:596–608

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